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<urn:uuid:e162e342-2e90-4a7f-971c-e0a541364e15> | seed | Strategies for Managing Opportunistic Infections
HIV (human immunodeficiency virus) infects the cells of your body's immune system. It then impairs how they function and eventually kills them over time. This gradually weakens your immune system, and your body then loses its ability to fight disease. While HIV is the cause, most people who die of AIDS do not die of HIV per se. They die from the infections that the body can no longer control due to a weakened immune system. Fairly common infections, which may cause little or no harm in a healthy person, take the opportunity of a weakened immune system to cause serious and even life-threatening disease. This is why they're called opportunistic infections, or OIs.
Dealing with OIs is an important part of a long-term plan for managing your HIV disease. The text over the next four pages explains in detail the different parts of an OI strategy, which includes:
The Centers for Disease Control (CDC) has developed a list of serious and life-threatening diseases, listed in the chart. When these diseases occur in HIV-positive people, they're called AIDS-defining OIs. (AIDS is short for acquired immune deficiency syndrome.) So when a person has an AIDS-defining OI, it results in the diagnosis of AIDS for that person. Another way an AIDS diagnosis occurs is when tests that measure your immune system show that you're at serious risk for developing these conditions. Examples of this include CD4 counts below 200 or CD4 percentages below 14%.
OIs can be fairly common infections, like genital herpes. But not everyone with HIV who has a herpes outbreak is deemed to have AIDS. To the contrary, herpes becomes an OI only when it takes advantage of a weakened immune system to become more aggressive, persistent and harder to treat. So, having HIV and genital herpes isn't automatically considered AIDS; but, having HIV and a herpes outbreak that persists for a month despite treatment is.
It's important to note that nearly any condition or disease can become opportunistic due to a weakened immune system. This is true for people living with cancers or other health problems. But for an OI to be the cause for an AIDS diagnosis, it must be one of the CDC's AIDS-defining diseases in people living with HIV.
However, it's possible for people with HIV to get conditions that are not on the CDC's list. Occasionally the CDC revises its list to include these new conditions. For example, hepatitis C (HCV) disease is not currently an AIDS-defining OI. But more data are showing that people with HIV are at higher risk for more aggressive HCV liver disease. Your first line of defense to many of these conditions is prevention.
Some OIs can be prevented. For example, people who have never been exposed to herpes can practice safer sex to reduce their risk of getting genital herpes. If you're not infected with the herpes virus, then there's no worry of it becoming an OI or threatening to your health. Project Inform's publication, Sex and Prevention Concerns for Positive People, contains information on how you can prevent many of these infections.
You can reduce your risk of some infections by practicing safer sex. Others can be prevented with vaccines. Still others can be avoided by handling and preparing food more safely or by being aware of and avoiding (when possible) the things that cause disease. This might include not handling birds or cats, even those kept as pets. It may also include using gloves when changing cat litter boxes, or having someone else deal with the litter.
Recently, outbreaks of drug-resistant staph skin infections have occurred. This infection can be spread through casual contact. Because these organisms are resistant to drugs, treatment may require intravenous therapy. Some speculate that in urban areas staph infections may be spread through something as simple as sharing equipment at the gym. Doing something as simple as putting a towel on gym equipment before using it, and not using that towel to wipe sweat from your body, may help you prevent a staph infection.
Preventing exposure to organisms is a great way to reduce your risk of getting an OI. In some cases, however, the organisms that cause OIs are in your every day environment. You may not be able to avoid them, or you may have already been exposed to them.
People living with HIV should be screened for many OIs when they first find out they're HIV-positive, as part of their early lab screenings. In some cases, this allows people to know if they're already exposed to an organism and helps them learn how to prevent infections they don't already have. (For more information on these types of lab tests, call Project Inform's Infoline at 1-800-822-7422.)
However, in the case of Pneumocystis jiroveci pneumonia (also called PCP), it's simply not known how the organism is spread. It's assumed that most people are already infected with it. In that case, preventive treatment is routinely used if your immune system weakens and as the risk for PCP increases. PCP remains the leading cause of death of people with AIDS in the US and is largely preventable.
Project Inform's Opportunistic Infections Chart sums up the Federal Guidelines for treating major OIs. Because HIV replicates more as your immune system battles infections, treating them as they occur is critical not only in dealing with the infections, but also curbing further damage to the immune system by HIV. This is true whether or not the infection is an actual OI. When it comes to OIs, however, and many issues in later-stage HIV disease, diagnosing some infections can be difficult.
One of the biggest challenges in treating OIs is early diagnosis, before they're able to take hold in different organs like the lungs, colon, brain, bone marrow, etc. The earlier something is diagnosed and treated, the more likely treatment will be successful and result in full recovery. This means regular checkups by your doctor (at least every three months) and talking to him or her about your symptoms.
If you experience any new or unusual symptoms and are between doctor visits, make an appointment. Don't wait three months to have something looked at. Keep a health journal or diary, or merely write on a calendar when a new or unusual symptom occurs and record how long it remains. This may help your doctor figure out if a symptom is a drug side effect, a sign of an OI or something else.
Many OIs have the same symptoms, and some infections may be masking others. So, initial treatment may only deal with part of a problem, but not the whole problem. Dealing successfully with multiple infections may take diligence on your part when seeing many doctors and specialists. It's ideal to have your primary doctor take charge, talking with your other doctors to make sure they're talking to each other.
The hardest part of dealing with multiple conditions is that doctors often aren't very good about talking to each other. It can easily become a full time job juggling your appointments as your different doctors order many different lab tests. It's your primary doctor's job to manage all of this, even when he or she is busy. Especially when many problems occur together, preparing for your appointments, writing down your questions beforehand, and having someone like an advocate with you to record the answers is strongly encouraged.
Once a condition is diagnosed, completing your treatment is vital. Also, drugs that treat some OIs may interact with your HIV meds. Any time a new treatment is added to your regimen, it's wise for you and your doctor to assess whether it's safe to use with your other meds and make any necessary dose adjustments.
OIs are generally not a problem for people whose CD4 cell counts remain stable above 200. It is extremely rare for people living with HIV to die of AIDS when their CD4 counts are above 200. However, as CD4 counts decline your risk for getting OIs increases.
Perhaps the best strategy for preventing OIs is to keep your CD4 counts above 200. Therefore, the Federal Guidelines for using HIV therapy recommend that people consider starting HIV therapy when their CD4 counts are 350 or below. They also strongly recommend treating anyone with symptoms of HIV disease (regardless of CD4 counts) and anyone with CD4 counts of 200 or below. This is because HIV therapy stops HIV from destroying immune cells, preventing the further decline of the immune system.
There are also Federal Guidelines for preventing and treating HIV-related OIs. A summary of these guidelines is available in Project Inform's publication, Opportunistic Infections Chart.
In general, if CD4 counts fall to 200 or below (or CD4 percentage below 14%), people are at increased risk for PCP. Preventive therapy is advised. For people with other symptoms of HIV infection, especially repeated fungal (candida) infections, PCP preventive therapy is often started when CD4 counts are higher, around 300. If CD4 counts fall to the 100-150 range, preventive therapy for toxoplasmosis is recommended for people who are positive for it. If CD4 counts fall to 50 or below, preventive therapy for MAC and CMV is advised. For people who suspect they've been exposed to tuberculosis, preventive therapy is warranted.
After treating an OI, it's sometimes necessary to take medications for life to prevent it from coming back. This is called maintenance therapy. In some cases, maintenance therapy may be stopped if a person's immune system recovers and sustains its control of HIV with the use of HIV therapy. The guidelines around starting and stopping maintenance therapy are outlined in Project Inform's publication, Opportunistic Infections Chart.
Some people with repeated herpes outbreaks will take long-term anti-herpes drugs to prevent them from coming back. Similarly, some people troubled with repeated fungal infections will take long-term anti-fungal drugs. However, in both cases maintenance therapy is somewhat controversial. This is because these organisms can develop resistance to the drugs, leaving few treatment options if or when a serious infection occurs.
When herpes or fungal infections continue to happen, it may come down to a quality of life issue. Long-term therapy may be the only viable option for a person. Carefully weighing the risks and benefits of these approaches is critical to making the right choice. Some will choose to risk losing viable treatment options to ease the problems of recurrent infections. Others will simply choose to treat these infections as they happen in hopes of preserving the benefits of therapy.
Regardless of where you are in your HIV disease, there are things that you can do to prevent and treat OIs. Preventing OIs applies to people at all stages of HIV disease. It includes:
A plan for treating OIs includes:
Candidiasis (thrush) of the throat (esophagus, trachea) or lungs
Cervical cancer, invasive and/or recurrent
Coccidioidomycosis, outside the lungs and/or throughout the body
Cryptococcosis, outside the lungs
Cryptosporidiosis with diarrhea that lasts longer than one month
Cytomegalovirus (CMV) disease of an organ other than the liver, spleen or lymph nodes, including in the eye (CMV retinitis)
Herpes simplex virus (HSV) outbreak lasting over one month, or HSV infections in the lungs/throat
Histoplasmosis, outside the lungs and/or throughout the body
HIV encephalopathy ("HIV dementia" or "AIDS dementia")
HIV wasting syndrome
Isosporiasis with diarrhea that lasts more than one month
Kaposi's sarcoma (KS)
Lymphoma of the brain
Lymphoma -- Burkitt or non-Burkitt type
Lymphoma -- immunoblastic type
Mycobacterium tuberculosis (TB) disease
Mycobacterium avium complex (MAC) or M. kansasii disease, outside the lungs and/or throughout the body
Mycobacterium disease of unknown type, outside the lungs and/or throughout the body
Pneumocystis jiroveci pneumonia (PCP)
Progressive multifocal leukoencephalopathy (PML)
Salmonella septicemia, recurrent
Toxoplasmosis of the brain in people older than one month of age
Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents
This article was provided by Project Inform. Visit Project Inform's website to find out more about their activities, publications and services. |
<urn:uuid:df811cb4-52e8-4bb3-b721-b91268a46e05> | seed | Summary of preferred terminology for use in HIV/AIDS reporting
HIV and AIDS
Use the term that is most specific and appropriate in the context. Examples include people living with HIV, HIV prevalence, HIV prevention, HIV testing, HIV-related disease; AIDS diagnosis, children made vulnerable by AIDS, children orphaned by AIDS, the AIDS response, national AIDS programme, AIDS service
organization. Both HIV epidemic and AIDS epidemic are acceptable.
There is no “AIDS virus”. The virus associated with AIDS is called the Human Immunodeficiency Virus, or HIV. Please note: “virus” in the phrase “HIV virus” is redundant. Use HIV.
Avoid the term infected. No one can be infected with AIDS, because it is not an infectious agent. AIDS is a surveillance definition meaning a syndrome of opportunistic infections and diseases that can develop as immunosuppression deepens
along the continuum of HIV infection from primary infection to death. Use person living with HIV or HIV-positive person.
There is no test for AIDS. Use HIV or HIV antibody test.
The word “victim” is disempowering. Use person living with HIV. Use the term AIDS only when referring to a person with a clinical AIDS diagnosis.
Use the term patient only when referring to a clinical setting. Use: patient with advanced HIV-related illness (or disease) or AIDS-related illness (or disease).
Use risk of HIV infection; risk of exposure to HIV.
Use key populations at higher risk (both key to the epidemic’s dynamics and key to the response). Key populations are distinct from vulnerable populations, which may be subject to societal pressures or social circumstances which may make them more vulnerable to exposure to infections, including HIV.
Use sex work or commercial sex or the sale of sexual services.
Use only in respect to juvenile prostitution; otherwise use sex worker.
Use injecting drug user. Drugs may be injected subcutaneously, intramuscularly or intravenously.
Use using non-sterile injecting equipment if referring to risk of HIV exposure; use using contaminated injecting equipment if the equipment is known to contain HIV or if HIV transmission has occurred.
Use response to AIDS. Use evidence-informed.
Use HIV prevalence. The word “rates” connotes the passage of time and should not be used in most instances.
Please spell out all abbreviations in full.
Background for commonly used terms and abbreviations
Prevention strategies: abstain from penetrative sexual intercourse (also used to indicate delay of sexual debut); be faithful (reduce the number of partners or have sexual relations with only one
partner); condomize (use male or female condoms consistently and correctly). ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) Not…immune deficiency. . .
As a verb: write ‘advocate change’ (rather than advocate for change).
This term is often used to mean any person living with HIV. However, it is stigmatizing and offensive
to many people living with the virus. It is also incorrect, since the agent being carried is HIV not AIDS.
AIDS- or HIV-RELATED ILLNESS OR DISEASE
Although ‘the person died of AIDS’ is commonly said or written, actually people do not die of AIDS, they die of HIV-related or AIDS-related disease. The expression AIDS-related illness can be
used if a person has an AIDS diagnosis.
The terms AIDS response, HIV response, response to AIDS and response to HIV are often used interchangeably to mean the response to the epidemic.
Since AIDS is a syndrome, it is incorrect to refer to the virus as the “AIDS virus”. HIV (the human immunodeficiency virus) is what ultimately causes AIDS (acquired immunodeficiency syndrome).
In referring to the virus, write the full expression at first usage and then use HIV; avoid the term HIV virus (which is a tautology, i.e. it is saying the same thing twice).
Spell out in full, i.e. antiretroviral therapy or antiretroviral treatment. The term ART can be used if it clearly refers to a triple antiretroviral drug combination.
BEHAVIOUR CHANGE (NOT ‘Behavioural Change’)
There are a number of theories and models of human behaviour that guide health promotion and education efforts to encourage behaviour change, i.e. the adoption and maintenance of healthy
Alternative term for voluntary counselling and testing (VCT). All HIV testing must be carried out under conditions of the “three Cs”: i.e. that it be confidential, accompanied by counselling and
conducted only with informed consent.
CONTAMINATED and NON-STERILE
Drug injecting equipment was “contaminated” if it caused infection, that is, the equipment contained HIV; “unclean”, “dirty” or “non-sterile” if it carried the risk of HIV exposure: that is, it may or may not have carried the virus.
The Joint United Nations Programme on HIV/AIDS (UNAIDS) has the following ten cosponsors, listed in the following order (according to UN rules): United Nations High Commissioner for Refugees (UNHCR) http://www.unhcr.org/ United Nations Children’s Fund (UNICEF) http://www.unicef.org/ World Food Programme (WFP) http://www.wfp.org/ United Nations Development Programme (UNDP) http://www.undp.org/ United Nations Population Fund (UNFPA) http://www.unfpa.org/ United Nations Office on Drugs and Crime (UNODC) http://www.unodc.org/odccp/index.html International Labour Organization (ILO) http://www.ilo.org/ United Nations Educational, Scientific and Cultural Organization (UNESCO)
http://www.unesco.org/ World Health Organization (WHO) http://www.who.int/en/ World Bank http://www.worldbank.org/
Country Response Information System. Developed by UNAIDS, CRIS provides partners in the global response to HIV with a user-friendly system consisting of an indicator database, a programmatic database, a research inventory database and other important information. The indicator database provides countries with a tool for reporting on national follow-up to the United
Nations General Assembly Special Session on HIV/AIDS (June 2001) Declaration of Commitment on HIV/AIDS. The country-level CRIS will be complemented by a Global Response Information Database (GRID), which will support strategic analysis, knowledge-based policy formulation and subsequent programming. At country and global levels a Research Inventory Database (RID) is also being developed.
Familiar terms used in some cultures may not be appropriate in other cultural contexts e.g. seasons of the year—avoid “fall” or “autumn” and prefer instead last quarter of the year or instead of summer prefer mid-year. Similarly remember that different cultures celebrate the New Year at different times and that seasons in the northern and southern hemispheres are opposite to each other.
AIDS is often referred to as a “deadly, incurable disease”, but this creates a lot of fear and only serves to increase stigma and discrimination. It has also been referred to as a “manageable, chronic illness, much like hypertension or diabetes”, but this may lead people to believe that it is not as serious as they thought. It is preferable to use the following description: AIDS, the acquired immunodeficiency syndrome, is a fatal disease caused by HIV, the human immunodeficiency virus. HIV destroys the body’s ability to fight off infection and disease, which can ultimately lead to death.
Currently, antiretroviral drugs slow down replication of the virus and can greatly enhance quality of life, but they do not eliminate HIV infection.
The term relates to the structural and social factors, such as poverty, gender, and human rights abuses that can increase people’s vulnerability to exposure to HIV. It is often reserved to describe underlying determinants.
In epidemiology, an epidemic is a disease that appears as new cases in a given human population (e.g. everyone in a given geographic area; a university, or similar population unit; or everyone of a certain age or sex, such as the children or women of a region) during a given period, at a rate that greatly exceeds what is “expected” based on recent experience. Defining an epidemic is subjective, depending in part on what is “expected”. An epidemic may be restricted to one locale (an outbreak), more general (an epidemic) or global (a pandemic). Common diseases that occur at a constant but relatively high rate in the population are said to be “endemic”. Widely known examples of epidemics include the plague of mediaeval Europe known as the Black Death, the influenza pandemic of 1918–1919, and the current HIV epidemic which is increasingly described as a pandemic (made up of distinct types of epidemics in areas across the globe).
Epidemiology is the branch of medical science that deals with the study of the incidence, distribution and determinants of patterns of a disease as well as its prevention in a population.
This term is preferred to evidence based in recognition of the fact that several elements may play a role in decision making, only one of which may be evidence; others may include cultural appropriateness, cost, feasibility and concerns about equity and so on.
Faith-based organization is the term preferred instead of e.g. church, synagogue, mosque or religious organization, as it is inclusive (non-judgmental about the validity of any expression of faith) and moves away from historical (and typically European) patterns of thought.
Referring to the pandemic, feminization is now often used by UNAIDS and others to indicate the increasing impact that it has on women. It is often linked to the idea that the number of women
infected has equalled, or surpassed, the figure for men or that women and girls are bearing the brunt of the epidemic in many settings.
Avoid using words such as “fight” and other combatant language e.g. struggle, battle, campaign or war, unless in a direct quotation. Alternatives include: response to; management of; measures against; initiative; action; efforts; and programme. One rationale for this is to avoid a transference being made from the fight against HIV to a fight against people living with HIV.
Write “men who have sex with men” unless individuals or groups specifically self-identify as
gay. The broader community of men and women and transsexuals should be described as lesbian, gay, bisexual and transgendered—the abbreviation LGBT is often used for such communities, but
UNAIDS’ general preference is to spell out all terms in full.
GENDER and SEX
The term “sex” refers to biologically determined differences, whereas the term “gender” refers to differences in social roles and relations between men and women. Gender roles are learned through socialization and vary widely within and between cultures. Gender roles are also affected by age, class, race, ethnicity and religion, as well as by geographical, economic and political environments. Since many languages do not have the word gender, translators may have to consider other alternatives to distinguish between these concepts.
GLOBAL FUND TO FIGHT AIDS, TUBERCULOSIS AND MALARIA
The Global Fund to Fight AIDS, Tuberculosis and Malaria, established in 2001, is an independent public-private partnership. Its purpose is to attract, manage and disburse additional resources to make a sustainable and significant contribution to mitigate the impact caused by HIV, tuberculosis and malaria in countries in need, while contributing to poverty reduction as part of the Millennium Development Goals. Since 2001, the Global Fund has attracted US$ 4.7 billion in financing through 2008. In September 2007, donors provided initial pledges to the Global Fund worth US$ 9.7 billion over three years. These pledges constitute the largest single financing exercise for health ever and they will allow the Global Fund to move towards annual commitments of US$ 6–8 billion by 2010. http://www.theglobalfund.org/en/
An acronym for the “greater involvement of people living with HIV/AIDS”. In 1994, 42 countries prevailed upon the Paris AIDS Summit to include the Greater Involvement of People Living with
HIV/AIDS Principle (GIPA) in its final declaration. http://www.unaids.org/en/Issues/Affected_communities/gipa.asp
UNAIDS does not use the term “high-risk group” because it implies that the risk is contained within the group whereas, in fact, all social groups are interrelated. It may also lull people who don’t identify with such groups into a false sense of security. As well it can increase stigma and discrimination. It is often more accurate to refer directly to “higher risk of HIV exposure”, “sex without a condom”, “unprotected sex”, or “using non-sterile injection equipment” rather than to generalize by saying “highrisk
Membership of groups does not place individuals at risk, behaviours may. In the case of married and cohabiting people, particularly women, it may be the risk behaviour of the sexual partner that places them in a “situation of risk”. There is a strong link between various kinds of mobility and heightened risk of HIV exposure, depending on the reason for mobility and the extent to which people are removed from their social context and norms. UNAIDS prefers the term “key populations” because it emphasizes that these populations, while being important to the dynamics of HIV transmission in a setting, are equally essential partners for an effective response to the epidemic.
HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART)
This term is now infrequently used in favour of antiretroviral treatment or therapy (ART). It referred to treatment regimens recommended by leading HIV experts to aggressively suppress viral replication and slow the progress of HIV disease. The usual HAART regimen combines three or more different drugs such as two nucleoside reverse transcriptase inhibitors and a protease inhibitor, two nucleoside analogue reverse transcriptase inhibitors and a non-nucleoside reverse transcriptase inhibitor or other combinations. More recently, new drugs have been developed to prevent the virus from entering the cell. These treatment regimens have been shown to reduce the amount of virus so that it becomes undetectable in a patient’s blood.
The Heavily Indebted Poor Countries Initiative is a debt relief tool for increasing the funds that countries have available and for ensuring that they are channelled to core human development
priorities, such as basic health care. The HIPC initiative, created in 1996 by the World Bank and further enhanced in 1999, has already helped some of the poorest nations in the world to free up precious resources for human development that would otherwise have been spent on servicing debt.
Fully funded and implemented, the enhanced HIPC initiative has the potential to be an even more powerful tool to allow countries to devote more resources to combating infectious diseases.
Symptoms of HIV infection may occur both at the beginning of HIV infection and after immune compromise sets in, leading to AIDS. During the initial infection with HIV, when the virus comes
into contact with the mucosal surface, it finds susceptible target cells and moves to lymphoid tissue where massive production of the virus ensues. This leads to a burst of high-level viraemia (virus in the bloodstream) with wide dissemination of the virus. Some people may have flu-like symptoms at this stage but these are generally referred to as symptoms of primary infection rather than HIV-related disease. The resulting immune response to suppress the virus is only partially successful and some virus escapes and may remain undetectable, sequestered in reservoirs for months to years.
As crucial immune cells, called CD4+ T cells, are disabled and killed, their numbers progressively
decline. In this manner, HIV-related disease is characterized by a gradual deterioration of immune function. Eventually high viral turnover leads to destruction of the immune system, sometimes
referred to as advanced HIV infection, which leads to the manifestation of AIDS.
As distinct from HIV-positive (which can sometimes be a false positive test result, especially in infants up to 18 months of age), the term HIV-infected is usually used to indicate that evidence of
HIV has been found via a blood test.
Showing no evidence of infection with HIV (e.g. absence of antibodies against HIV) in a blood or oral fluid test. Synonymous with seronegative. An HIV-negative person can be infected if he or she is in the window period between HIV exposure and detection of antibodies.
Showing indications of infection with HIV (e.g. presence of antibodies against HIV) in a blood or oral fluid test. Synonymous with seropositive. Results may occasionally be false positive.
HUMAN IMMUNODEFICIENCY VIRUS (HIV)
The virus that weakens the immune system, ultimately leading to AIDS. Since HIV means “human immunodeficiency virus”, it is redundant to refer to the HIV virus.
HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (HIV-1)
The retrovirus isolated and recognized as the etiologic (i.e. causing or contributing to the cause of a disease) agent of AIDS. HIV-1 is classified as a lentivirus in a subgroup of retroviruses. Most viruses
and all bacteria, plants and animals have genetic codes made up of DNA, which is transcribed into RNA to build specific proteins. The genetic material of a retrovirus such as HIV is the RNA itself. The viral RNA is reverse transcribed into DNA, which is then inserted into the host cell’s DNA preventing the host cell from carrying out its natural functions and turning it into an HIV factory.
HUMAN IMMUNODEFICIENCY VIRUS TYPE 2 (HIV-2)
A virus closely related to HIV-1 that has also been found to cause AIDS. It was first isolated in West Africa. Although HIV-1 and HIV-2 are similar in their viral structure, modes of transmission
and resulting opportunistic infections, they have differed in their geographical patterns of infection and in their propensity to progress to illness and death. Compared to HIV-1, HIV-2 is found primarily in West Africa and has a slower, less severe clinical course.
HIV incidence (sometimes referred to as cumulative incidence) is the number of new cases arising in a given period in a specified population. UNAIDS normally refers to the number of people (of
all ages) or children (0–14 years) who have become infected during the past year. In contrast HIV prevalence refers to the number of infections at a particular point in time (like a camera snapshot). In specific observational studies and prevention trials, the term incidence rate is used to describe incidence per hundred person years of observation.
INJECTING DRUG USERS (IDUs)
This term is preferable to drug addicts or drug abusers, which are seen as derogatory terms and which often result in alienation rather than creating the trust and respect required when dealing with
those who inject drugs. UNAIDS does not use the term “intravenous drug users” because subcutaneous and intramuscular routes may be involved. It is preferable to spell out in full and not use the abbreviation. An acceptable alternate phrasing is people who inject drugs.
This term conveys “doing something to someone or something” and as such undermines the concept of participatory responses. Preferred terms include programming, programme, activities, initiatives, etc.
MILLENNIUM DEVELOPMENT GOALS (MDGs)
Eight goals developed at the Millennium Summit in September 2000. Goal 6 refers specifically to AIDS but attainment of several goals is being hampered by the HIV epidemic. http://www.un.org/millenniumgoals/
MONITORING AND EVALUATION REFERENCE GROUP
Established by UNAIDS, the Monitoring and Evaluation (M&E) Reference Group (MERG) has a broad membership of national, bilateral agency and independent evaluation expertise, enabling it to assist in the harmonization of monitoring and evaluation approaches among collaborating organizations
and in the development of effective monitoring and evaluation of the response to the epidemic.
Abbreviation for “men who have sex with men” or “males who have sex with males”. This term is useful as it includes not only men who self identify as gay or homosexual and have sex only with other men but also bisexual men, and heterosexual men who may, nonetheless at times have sex with other men.
Abbreviation for “mother-to-child transmission” (PMTCT is the abbreviation for “prevention of mother-to-child transmission”). Some countries prefer the term “parent-to-child transmission” to
avoid stigmatizing pregnant women and to encourage male involvement in HIV prevention.
Illnesses caused by various organisms, some of which usually do not cause disease in persons with healthy immune systems. Persons living with advanced HIV infection may have opportunistic
infections of the lungs, brain, eyes and other organs. Opportunistic illnesses common in persons diagnosed with AIDS include Pneumocystis carinii pneumonia, cryptosporidiosis, histoplasmosis, bacterial infections, other parasitic, viral and fungal infections; and some types of cancers. Tuberculosis
is the leading HIV-associated opportunistic infection in developing countries.
In the context of AIDS, it is preferable to say “children orphaned by AIDS” or “orphans and other children made vulnerable by AIDS”. Referring to these children as “AIDS orphans” not only stigmatizes them, but also labels them as HIV-positive, which they may not necessarily be. Identifying a human being by his/her medical condition alone also shows a lack of respect for the individual.
Contrary to traditional usage UNAIDS uses “orphan” to describe a child who has lost either one or
A disease that spreads across an entire region, continent or the whole world. Preferred usage is to write “pandemic” when referring to global disease and to use “epidemic” when referring to country or regional level. For simplicity, UNAIDS often uses “epidemic”,
An agent causing disease.
PEOPLE LIVING WITH HIV
Avoid the expression “people living with HIV and AIDS” and the abbreviation PLWHA. With reference to those living with HIV, it is preferable to avoid certain terms: AIDS patient should only
be used in a medical context (most of the time, a person with AIDS is not in the role of patient); the term AIDS victim or AIDS sufferer implies that the individual in question is powerless, with
no control over his or her life. It is preferable to use “people living with HIV” (PLHIV), since this reflects the fact that an infected person may continue to live well and productively for many years.
Referring to people living with HIV as innocent victims (which is often used to describe HIV-positive children or people who have acquired HIV medically) wrongly implies that people infected in
other ways are somehow deserving of punishment. It is preferable to use “people living with HIV”, or “children with HIV”.
Usually given as a percentage, HIV prevalence quantifies the proportion of individuals in a population who have HIV at a specific point in time. UNAIDS normally reports HIV prevalence among adults, aged 15–49 years. We do not write prevalence rates because a time period of observation is not involved. “Prevalence” is sufficient, e.g. the Caribbean region, with estimated adult HIV prevalence of 2.3% in 2003, is an area to focus on in the future”. HIV prevalence can also refer to the number of people living with HIV as in “by December 2007 an estimated 33.2 million people were living with HIV worldwide.
Use this term in respect to juvenile prostitution only. Otherwise for people of older ages use “commercial sex” “sex work” or “the sale of sexual services”.
Under certain circumstances, when an individual is seeking medical care, HIV testing may be offered. It may be diagnostic—as when a patient presents with symptoms that may be attributable to HIV or has an illness associated with HIV such as tuberculosis—or it may be a routine offer to an asymptomatic person. For example, HIV testing may be offered as part of the clinical evaluation of patients with sexually transmitted infections and pregnant women. HIV testing may be offered to all patients where HIV is prevalent. Regardless of the type of testing and the location of the offer,
All HIV testing should always be carried out under conditions respecting the three Cs—confidentiality, informed consent and counselling. Testing without counselling has little impact on behaviour and is a significant lost opportunity for assisting people to avoid acquiring or transmitting infection.
Avoid using the expressions “groups at risk” or “risk groups”. People with behaviours which may place them at higher risk of exposure to HIV do not necessarily identify themselves with any
particular group. Risk refers to risk of exposure to HIV which may be high as a result of specific behaviours or situations. Examples of the latter include risk in discordant couples unaware of their
serostatus and recipients of unscreened blood or blood products. Behaviours, not memberships, place individuals in situations in which they may be exposed to HIV. Some populations may be at
increased risk of exposure to HIV.
RISK COMPENSATION or RISK ENHANCEMENT
A compensatory increase in behaviours which can result in exposure to HIV brought on by reduced perception of personal risk e.g. uptake of a 50% effective preventive HIV vaccine might tend to encourage abandoning condom use.
Use by preference the term safer sex because the term safe sex may imply complete safety. Sex is 100% safe from HIV transmission when both partners know their HIV-negative serostatus and
neither partner is in the window period between HIV exposure and appearance of HIV antibodies detectable by the HIV test. In other circumstances, reduction in the numbers of sexual partners and
correct and consistent use of male or female condoms can reduce the risk of HIV transmission. The term safer sex more accurately reflects the idea that choices can be made and behaviours adopted to reduce or minimize risk.
As related to HIV infection, the proportion of persons who have serologic evidence of HIV infection, i.e. antibodies to HIV at any given time.
A generic term that refers to the presence/absence of antibodies in the blood. Often, the term refers to HIV antibody status.
SEXUALLY TRANSMITTED INFECTION (STI)
Also called venereal disease (VD), an older public health term, or sexually transmitted disease (STD), terms that do not convey the concept of being asymptomatic in the same way that the term sexually transmitted infection does. Sexually transmitted infections are spread by the transfer of organisms from person to person during sexual contact. In addition to the “traditional” STIs (syphilis and gonorrhoea), the spectrum of STIs now includes HIV, which causes AIDS; Chlamydia trachomatis; human papilloma virus (HPV) which can cause cervical, penile or anal cancer; genital herpes; chancroid; genital mycoplasmas; hepatitis B; trichomoniasis; enteric infections; and ectoparasitic diseases (i.e.
diseases caused by organisms that live on the outside of the host’s body). The complexity and scope of sexually transmitted infections have increased dramatically since the 1980s; more than 20 diseasecausing organisms and syndromes are now recognized as belonging in this category.
“Commercial sex work” is considered a tautology, which is saying the same thing twice over in different words. Preferred terms are “sex work”, “commercial sex”, and “the sale of sexual services”.
The term “sex worker” is intended to be non-judgmental, focusing on the conditions under which sexual services are sold. Alternate formulations are: “women/men/people who sell sex”. Clients of
sex workers may then also be called “men/women/people who buy sex”. The term “commercial sex worker” is no longer used, primarily because it is considered to be saying something twice over in different words (i.e. a tautology).
When referring to injecting equipment UNAIDS does not use the word “sharing” in its publications. Instead, “use of contaminated injecting equipment” is preferred if referring to actual
HIV transmission and “use of non-sterile injecting equipment” if referring to risk of HIV exposure. This is because injecting drug users uncommonly “share” their needles in the usually understood
sense of the word—with the exception of sexual partners who inject together. In the absence of needle exchanges, people may use discarded needles (which are anonymous) or bargain away
drugs for a needle or are injected by professional injectors. They do not regard this as sharing.
Neither does “sharing” distinguish between needle borrowing and needle lending; this is important because (usually) different dynamics are at work. A person aware of his or her HIV-positive status may try to avoid lending, but may continue to borrow or vice versa. Also “sharing” has positive connotations in injecting drug use communities (and wider communities also), e.g. sharing a meal, which are not appropriate in writing about HIV risk.
STIGMA and DISCRIMINATION
As the traditional meaning of stigma is a mark or sign of disgrace or discredit, the correct term would be stigmatization and discrimination; however, “stigma and discrimination” has been accepted in everyday speech and writing, and may be treated as plural.
Continual analysis, interpretation and feedback of systematically collected data, generally using methods distinguished by their practicality, uniformity, and rapidity rather than by accuracy or
Sometimes used to indicate transmission of a pathogen such as HIV from mother to fetus or baby during pregnancy or birth but may be used to refer to the genetic transmission of traits. UNAIDS
primarily uses the term mother-to-child transmission.
Word Of The Day - Improve Your Knowledge
Word of the Day
|Definition:||Equipment, such as clothing, tools, or instruments, used for a specific purpose or task.|
Quote of the Day
Every traveler has a home of his own, and he learns to appreciate it the more from his wandering. |
<urn:uuid:fc0d9d05-36b4-4614-a03e-f353c5de4d1f> | seed | How It Works
Olive leaf has a wide number of constituents, including oleuropein and several types of flavonoids (e.g., rutin, apigenin, luteolin).11 While olive leaf is traditionally associated with a wide number of medicinal claims, few of these have been verified by experimental study. In an animal study oleuropein (when given by injection or in intravenous form) was found to decrease blood pressure (e.g., systolic and diastolic) and dilate the coronary arteries surrounding the heart.12 This ability to lower blood pressure may justify the traditional use of olive leaf in the treatment of mild to moderate hypertension.13 However, human studies are needed to clearly establish olive leaf as a potential treatment for high blood pressure.
In addition, a test tube study has revealed that oleuropein inhibits the oxidation of LDL (“bad”) cholesterol. LDL oxidation is one part in a series of damaging events that, if left unchecked, can lead to the development of atherosclerosis.14 This action may provide one clue as to why those consuming a Mediterranean-based diet may lower their risk of developing atherosclerosis.
Oleuropein from olives may also have antibacterial properties. When unheated olives are brined to preserve them, oleuropein is converted into another chemical called elenolic acid. Elenolic acid has shown antibacterial actions against several species of Lactobacilli and Staphylococcus aureus and Bacillus subtilus in a test tube study.15 Whether or not the oleuropein in the leaf undergoes such a transformation is open to question at this point, raising some question as to its antibacterial effects and potential use for this purpose in humans.
Olive leaf extracts have been employed experimentally to lower elevated blood-sugar levels in animals with diabetes.16 These results have not been reproduced in human clinical trials and as such, no clear conclusions can be made from this animal study in the treatment of diabetes.
How to Use It
The effective amount of olive leaf for human use is not established. To make a tea, steep 1 teaspoon (5 grams) of dried leaves in 1 cup (250 ml) of hot water for 10–15 minutes.17 Dried leaf extracts containing 6–15% oleuropein are available commercially, but no standard amount has been established.
Copyright © 2014 Aisle7. All rights reserved. Aisle7.com
The information presented in Aisle7 is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. Self-treatment is not recommended for life-threatening conditions that require medical treatment under a doctor's care. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires June 2015. |
<urn:uuid:8be1a4b4-46a1-4605-9246-cd93e6c59fc2> | seed | This information will help you understand mesothelioma, including risk factors, diagnosis, surgery, and treatment.
The main known risk factor for mesothelioma is exposure to asbestos, a mineral fiber that was commonly used in building construction. People who work in mining, milling, construction, plumbing, heating, insulation, and carpentry, as well as those who do electrical and shipyard work, generally have had greater exposure to asbestos than those in other fields. Therefore, they are at higher risk of developing mesothelioma. Family members of these workers are also at higher risk than others because they may have been exposed to asbestos in the clothes and hair of the workers.
Although asbestos is the most common risk factor for mesothelioma, people can develop it without being exposed to asbestos.Back to top
To see if you have mesothelioma, you will have a biopsy. A biopsy involves removing a small amount of tissue from the area where the cancer may be located. The tissue will be looked at under a microscope by a pathologist. A biopsy is usually done by thoracentesis, video-assisted thoracic surgery, or open lung biopsy. Your surgeon will discuss with you which approach is best for you.
Thoracentesis is a procedure in which a needle is used to remove fluid from your pleura (the space between your chest wall and your lung). It can be done in your doctor’s office or in a hospital.
Video-assisted thoracic surgery (VATS) is done in an operating room. A thin telescope attached to a video camera is inserted into your stomach through a small incision (surgical cut). Additional incisions are made and a surgical instrument is used to remove tissue.
Open lung biopsy is done in an operating room. Your surgeon will make a small incision between your ribs. A surgical instrument is then used to remove a piece of your pleura.
Your doctor may want you to have other tests, such as a computed tomography (CT) scan, a positron emission tomography (PET) scan, a stress test, a pulmonary function test (PFT), and a ventilation perfusion scan to see if the cancer has spread to other areas in your body and to test how your lungs are working. If you need to have any other tests, your doctor will discuss this with you.Back to top
Staging a cancer is a way of describing its location, whether it has spread, and whether it affects other organs. Staging will help your doctor make the best treatment choice for you.
- Stage I mesothelioma is when tumors are confined to the pleura.
- Stage II mesothelioma is when tumors have spread from the pleura to 1 lung.
- Stage III mesothelioma is when tumors have spread into the chest wall or involves the lymph nodes.
- Stage IV mesothelioma is when tumors have invaded the chest wall or have spread to other sites in the body.
Your treatment may include surgery, radiation therapy, and chemotherapy. Your healthcare team will make a treatment recommendation based on the stage of your cancer, how well your lungs are functioning, and your overall health.
Surgery is the most common treatment for mesothelioma. The goal of surgery is to remove all of the cancer. Depending on your surgery, you may have part or all of your pleura, lung, and linings of your diaphragm and pericardium (the sac surrounding your heart) removed.
Some patients may have a pleural effusion, which is when there is a buildup of fluid between the walls of the pleura. This can limit how much your lungs can expand, and can make you feel short of breath. Your doctor may do a procedure called a to help you breathe and feel more comfortable.
Radiation is the use of high energy x-rays to kill cancer cells and to help reduce the risk of recurrence (the cancer coming back). Your healthcare team will go over radiation planning, treatment, and possible side effects with you.
Chemotherapy is a medication or a combination of medications that is used to treat cancer. The most commonly used chemotherapy to treat mesothelioma includes 2 medications: pemetrexed (Alimta®) and cisplatin. Your healthcare team will discuss the benefits and risks of chemotherapy with you.
Your doctor may also recommend other medications or the possibility of joining a clinical trial.Back to top
The diagnosis and treatment of cancer can be a very stressful and overwhelming event. You may feel depressed, anxious, confused, afraid, or angry. You may have strong feelings about any permanent changes. These changes can have an impact on your emotional well-being. Help is available for you at any time. If you would like counseling, your nurse can give you a referral to see a social worker, psychiatrist, or counselor.
The Memorial Sloan Kettering Cancer Center (MSK) Resources for Life After Cancer (RLAC) Program provides support services after your treatment is finished. To learn more about these services, call 646-888-8106.
Also, you may find it comforting to speak with a cancer survivor or caregiver who has been through a similar treatment. Through our Patient-to-Patient Support Program, you have a chance to speak with former patients and caregivers. To learn more about this service, call 212-639-5007.Back to top
For additional online information, visit LIBGUIDES on MSKCC’s library website at http://library.mskcc.org or the mesothelioma cancer section of www.mskcc.org. You can also contact the library reference staff at 212-639-7439 for help.Back to top
If you have any questions or concerns, talk with a member of your healthcare team. You can reach them Monday through Friday from 9:00 am to 5:00 pm at ____________________. After 5:00 pm, during the weekend, and on holidays, please call____________________. If there’s no number listed, or you’re not sure, call 212-639-2000. |
<urn:uuid:1dc2f3cd-368d-4021-b3df-cd2c0f2f56d9> | seed | Identifying barriers to cancer survivorship programs
Identifying barriers to cancer survivorship programs
Advances in cancer screening have improved both early detection of the disease and treatment effectiveness. As a result, persons who would not have survived cancer may live many years after completing a prescribed plan of cancer treatment.1 Nurses and other medical professionals should be both compelled and obligated to offer services that address the multifaceted long-term effects of the physical, emotional, and financial burden of cancer and its treatment as it affects patients beyond primary treatment.
The need for oncology nurses to be involved in investigating, identifying, and overcoming the barriers to successful cancer survivorship programs is increasingly evident by the emerging societal awareness of cancer survivorship issues. With the knowledge gained from focused research on these issues, nurses can be a catalytic force in eliminating barriers that limit active participation in survivorship programs. Currently, several models exist for structuring survivorship programs, including the Lance Armstrong Livestrong Foundation, the National Coalition for Cancer Survivorship (NCCS), and the National Cancer Institute (NCI) Office of Cancer Survivorship. These organizations offer frameworks for patient-focused interventions from which nursing can assimilate plans of care that address the unique needs of the cancer survivor.
DEMOGRAPHICS OF SURVIVORSHIP
The NCI Surveillance Epidemiology and End Results (SEER) report, Cancer Statistics Review, predicts approximately 40.77% of people born today will develop some type of cancer during their lifetime.2 Furthermore, an estimated 66% of the approximately 11.7 million people living with a diagnosed cancer in the United States at the beginning of 2007 are expected to still be alive at least 5 years after their cancer diagnosis.2 In a 2010 study, Mariotto and colleagues reported health care costs for approximately 13.8 million cancer survivors was estimated at $124.57 billion.3 Their research concluded that current incidence and survival rates are expected to increase those estimates to 18.1 million cancer survivors at an annual cost of $157.77 billion by 2020.3
Patients who survive cancer beyond treatment often experience physical, social, emotional, financial, and spiritual changes as a direct result of their cancer diagnosis and treatment. Emerging post-cancer-treatment issues increase the need for nurses to understand how these changes relate to prevention of secondary disease, as well as a focus on patient health and efforts to prevent cancer recurrence. Patients' struggle with long-term effects of chemotherapy is potentially problematic over time. Delayed effects of chemotherapy often occur months and even years after treatment.
EVOLUTION OF SUPPORTIVE CARE
Support groups typically served as the traditional modality for addressing cancer-related care issues until the early 1990s. These groups promoted emotional support and helped patients cope with the fear of dying and disease recurrence; however, they did not address other aspects of ongoing post-cancer-treatment care.4 The paradigm of studying and providing cumulative and ongoing survivorship care has emerged through public awareness and scholarly interest. Current attention from professional organizations such as the Oncology Nursing Society (ONS), the American Society of Clinical Oncologists (ASCO), and the American Cancer Society (ACS), combined with efforts by grass roots consumer organizations such as the NCCS, the Lance Armstrong Livestrong Foundation, and the Susan G. Komen for the Cure Foundation have increased public awareness and advocacy for more research of cogent and modern cancer survivorship issues.
Oncology as a specialty has evolved significantly in the last half century. Historically, educational materials on cancer and chemotherapy were not readily available, and formalized support programs were nonexistent. Cancer and survivorship advocacy has expanded to models of self-organizational and public policy advocacy.5 The Office of Cancer Survivorship, created by the NCI in 1996, has continuously tasked investigators with research that would further define and improve quality of life issues for long-term cancer survivors.6 Depression, cognitive difficulties, fatigue, aches and pains, insomnia, and decline in social function and interaction are identified as lasting and progressive effects long after the initial cancer diagnosis.7
Unrecognized barriers hinder the implementation of successful cancer survivorship programs. A survey of 399 active ONS members showed only 27% of respondents were employed in a setting that had a formal, structured cancer survivorship program.8 The most significant barriers to survivorship care programs were a lack of funding and an inability to have designated clinical time allocated for cancer survivorship programs. In addition, clinical experience in oncology had an impact on knowledge of cancer survivorship. Forty-nine percent of respondents who had less than 5 years of experience in oncology reported a lack of sufficient knowledge about cancer survivorship compared with 36% of respondents who had more than 5 years of combined nursing oncology experience.8
Efforts should concentrate on identifying the variables that prohibit successful operation of community practice-based cancer survivorship programs, as well as the variables that might discourage patient enrollment and active participation. For example, many studies focus on survivorship concerns for pediatric patients with cancer; however, consistent guidelines for adult survivors of pediatric cancers are lacking.9 This gap is not only a barrier to complete care for these patients, but also illustrates a wide practice gap between clinical research and applicable models for nursing care. |
<urn:uuid:c62d1227-6838-4876-9ca5-28fb8e0687d8> | seed | Sarasota Memorial has added an important test to help people with colon or endometrial cancer determine their risk for Lynch syndrome, an inherited condition in which individuals and their family members are at greater risk for developing secondary cancers often at a young age.
In June, the hospital began testing tumor tissue samples from patients undergoing resections for colon cancer and hysterectomies for endometrial cancer. The Immunohistochemistry (IHC) test helps determine if individuals may have Lynch syndrome, also called hereditary nonpolyposis colorectal cancer (HNPCC), helping doctors make important decisions on the timing and delivery of care for patients with the hereditary cancer syndrome.
In the screening program’s first month, tissue samples from several patients revealed certain protein abnormalities indicating a strong probability for Lynch syndrome. The screening results are sent to each patient’s doctor for follow-up consultations.
“The screening test doesn’t diagnose an individual with Lynch syndrome, however, it can indicate a very strong probability that Lynch syndrome runs in their family,” said Sarasota Memorial’s Genetic Education Program Coordinator Cristi Radford, the only certified genetic counselor specializing in oncology between Tampa and Naples. “It’s important for those patients to talk to their doctor about genetic counseling. Routine surveillance and screenings can save not only their life, but also the lives of their family members.”
While most people have about a six percent chance of developing colon cancer at some point in their lives, people with Lynch syndrome have about an 80 percent chance. Women with Lynch syndrome also have about a 10 percent chance of developing ovarian cancer and a 60 percent chance of developing uterine cancer.
If you have a gene mutation that causes Lynch syndrome, on average at least another three family members will have it, Radford said. People who have Lynch syndrome have a high chance of developing cancer more than once in their lifetime, may have cancer at a younger age (under 50), and/or have a family history of certain cancers (see types below).
You or a relative could be at risk for Lynch syndrome if:
- You or your relative was diagnosed with colorectal or uterine cancer before age 50.
- You or your relative has had two or more Lynch syndrome cancers (colon, uterine, ovary, stomach, small intestine, pancreas, ureter, kidney or brain cancers).
- You’ve had an abnormal IHC screening test.
If you have been diagnosed with colon or endometrial cancer, or if you’re concerned about your family’s risk for Lynch syndrome or other hereditary cancer, call Sarasota Memorial’s Genetic Education Program: 917-2005 |
<urn:uuid:c30573d5-03cb-462a-a281-fa8f6ed9c095> | seed | Am Fam Physician. 2002 Mar 15;65(6):1190-1195.
Many proven and well-accepted preventive health measures are underused. Numerous systems have been proposed over the years to increase appropriate use of preventive care, but most meet with less than robust success. Dexter and associates conducted a randomized, controlled trial to determine the effects of computerized reminders on the rates at which preventive therapies are sought.
Over an 18-month period, the authors studied the use of a computerized reminder system in a general medicine service at an urban teaching hospital. They aimed to increase the use of four preventive health items (pneumococcal vaccination, influenza vaccination, prophylactic heparin for deep venous thrombosis prevention, and prophylactic aspirin). The study authors randomly assigned resident physicians and medical students to an intervention or a control group and followed their use of the targeted preventive health items on 10,065 consecutive hospital admissions.
All inpatient orders were made through a computerized order entry system at the study hospital. The intervention group received computer-generated reminders when inpatients were eligible for a given preventive health item. The ordering physicians and students could accept or decline the suggested items with one or two keystrokes on the computer. The control group was free to order any of the targeted items but received no reminders.
All four of the targeted preventive health items were ordered significantly more often by physicians and students in the intervention group. Pneumococcal vaccination was ordered for about 36 percent of eligible patients in the intervention group versus about 1 percent in the control group. Influenza vaccination rates were similar, with orders written for approximately 51 percent of appropriate patients in the intervention group versus 1 percent in the control group. The likelihood that ordering physicians and students would accept the reminders varied widely, with most accepting 11 to 40 percent of the suggested orders. Reminders were more likely to be accepted for older patients than for younger but appropriately eligible patients. The suggestion for use of prophylactic aspirin was more frequently accepted for patients hospitalized with myocardial infarction or unstable angina than other eligible diagnoses, such as cerebrovascular disease, peripheral vascular disease, and coronary risk factors.
The authors conclude that computer-generated reminders are successful in increasing the use of appropriate preventive health measures in hospitalized patients.
Dexter PR, et al. A computerized reminder system to increase the use of preventive care for hospitalized patients. N Engl J Med. September 27, 2001;345:965–70.
editor's note: In their discussion, the authors note a previous inpatient trial using computerized reminders at the same hospital that failed to increase the ordering of preventive health measures. Following that failure, the reminders in this trial were designed to generate pre-written orders that could be accepted or declined with a simple keystroke. The dictum that “an ounce of prevention is a ton of work” applies—interventions that allow physicians to easily incorporate preventive health practices in their usual workload are more likely to be successful. Computerization and an electronic medical record alone are not sufficient; a clever and efficient design is paramount.—b.z.
Copyright © 2002 by the American Academy of Family Physicians.
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<urn:uuid:9028b4c0-2377-4c5c-9842-f00222807867> | seed | (Lorion et al., 1987; Farrington, 1989; Yoshikawa, 1994; Catalano and Hawkins, 1996; Biglan et al., 2004).
Other studies of risk markers for serious delinquency reached similar conclusions. Porter and colleagues (1999) used data from the three projects of the Office of Juvenile Justice and Delinquency Prevention’s Program of Research on the Causes and Correlates of Delinquency in Denver, Pittsburgh, and Rochester. They compared three groups—nonoffenders, general but nonviolent delinquents, and violent delinquents—on 19 risk markers representing 7 domains—community, family structural characteristics, parent-child relations, school, peers, individual, and problem behaviors. They conclude that “there is not a different set of risk factors for serious violent offenders … [but] the serious violent offenders have greater deficits, or more extreme scores, on many of these risk factors as compared to general delinquents [and] are also more likely to experience risk in multiple domains” (Porter et al., 1999, p. 15). More recently, Esbensen and colleagues (2010) examined risk markers for serious delinquency in a sample of 5,935 eighth graders drawn from 11 different communities throughout the United States. They compared nonoffenders to nonviolent offenders and to serious violent offenders across 18 risk markers. In general, level of risk increased from nonoffenders to nonviolent offenders to violent offenders, but the differences appeared to be a matter of degree rather than kind. Similar results were also found when examining a high-risk sample of adolescents from Los Angeles (MacDonald, Haviland, and Morral, 2009). Once again, frequent and violent offenders differed from nonviolent and low-rate offenders, not in the presence of certain risk markers, but rather in that frequent and violent offenders had higher than average values across their baseline assessment of risk markers for delinquency, such as delinquent peers, family criminality, and substance use.
Comparing Delinquents and Nonoffenders
Few studies directly compare serious delinquents to both general delinquents and nonoffenders. Among those that do, however, the weight of the available evidence suggests that serious delinquents are influenced by the same risk markers and developmental processes as other youth. Some preliminary evidence of associations between neuropsychological or physiological indicators and serious adolescent offending exists (e.g., Cauffman, Steinberg, and Piquero, 2005), but there is no body of evidence of which we are aware to indicate that serious delinquents are qualitatively different from other delinquents who are involved in the juvenile justice system. They do commit more offenses and some more violent offenses, but that is because they appear to experience a greater accumulation of risk markers in comparison to others. But the individual risk markers that they experience, |
<urn:uuid:eed86e7e-081c-4879-8c73-5b9a8c668cef> | seed | October 21, 2014
Morgan Kelly, Office of Communications
When it comes to the brain, “more is better” seems like an obvious assumption. But in the case of synapses, which are the connections between brain cells, too many or too few can both disrupt brain function.
Researchers from Princeton University and the University of California-San Diego (UCSD) recently found that an immune-system protein called MHCI, or major histocompatibility complex class I, moonlights in the nervous system to help regulate the number of synapses, which transmit chemical and electrical signals between neurons. The researchers report in the Journal of Neuroscience that in the brain MHCI could play an unexpected role in conditions such as Alzheimer’s disease, type II diabetes and autism.
MHCI proteins are known for their role in the immune system where they present protein fragments from pathogens and cancerous cells to T cells, which are white blood cells with a central role in the body’s response to infection. This presentation allows T cells to recognize and kill infected and cancerous cells.
In the brain, however, the researchers found that MHCI immune molecules are one of the only known factors that limit the density of synapses, ensuring that synapses form in the appropriate numbers necessary to support healthy brain function. MHCI limits synapse density by inhibiting insulin receptors, which regulate the body’s sugar metabolism and, in the brain, promote synapse formation.
Researchers from Princeton University and the University of California-San Diego recently found that an immune-system protein called MHCI, or major histocompatibility complex class I, moonlights in the nervous system to help regulate the number of synapses, which transmit chemical and electrical signals between neurons. Pictured is a mouse hippocampal neuron studded with thousands of synaptic connections (yellow). The number and location of synapses — not too many or too few — is critical to healthy brain function. The researchers found that MHCI proteins, known for their role in the immune system, also are one of the only known factors that ensure synapse density is not too high. The protein does so by inhibiting insulin receptors, which promote synapse formation. (Image courtesy of Lisa Boulanger, Department of Molecular Biology)
Senior author Lisa Boulanger, an assistant professor in the Department of Molecular Biology and the Princeton Neuroscience Institute (PNI), said that MHCI’s role in ensuring appropriate insulin signaling and synapse density raises the possibility that changes in the protein’s activity could contribute to conditions such Alzheimer’s disease, type II diabetes and autism. These conditions have all been associated with a complex combination of disrupted insulin-signaling pathways, changes in synapse density, and inflammation, which activates immune-system molecules such as MHCI.
Patients with type II diabetes develop “insulin resistance” in which insulin receptors become incapable of responding to insulin, the reason for which is unknown, Boulanger said. Similarly, patients with Alzheimer’s disease develop insulin resistance in the brain that is so pronounced some have dubbed the disease “type III diabetes,” Boulanger said.
“Our results suggest that changes in MHCI immune proteins could contribute to disorders of insulin resistance,” Boulanger said. “For example, chronic inflammation is associated with type II diabetes, but the reason for this link has remained a mystery. Our results suggest that inflammation-induced changes in MHCI could have consequences for insulin signaling in neurons and maybe elsewhere.”
This image of a neuron from a mouse hippocampus shows insulin receptors (green) and the protein calbindin (red). In this area of the brain, calbindin is present in dentate granule cells, which form synapses on MHCI-expressing cells. The extensive overlap (yellow) suggests that this neuron, which expresses insulin receptors, is a dentate granule cell neuron. (Image courtesy of Lisa Boulanger, Department of Molecular Biology)
MHCI levels also are “dramatically altered” in the brains of people with Alzheimer’s disease, Boulanger said. Normal memory depends on appropriate levels of MHCI. Boulanger was senior author on a 2013 paper in the journal Learning and Memory that found that mice bred to produce less functional MHCI proteins exhibited striking changes in the function of the hippocampus, a part of the brain where some memories are formed, and had severe memory impairments.
“MHCI levels are altered in the Alzheimer’s brain, and altering MHCI levels in mice disrupts memory, reduces synapse number and causes neuronal insulin resistance, all of which are core features of Alzheimer’s disease,” Boulanger said.
Links between MHCI and autism also are emerging, Boulanger said. People with autism have more synapses than usual in specific brain regions. In addition, several autism-associated genes regulate synapse number, often via a signaling protein known as mTOR (mammalian target of rapamycin). In their study, Boulanger and her co-authors found that mice with reduced levels of MHCI had increased insulin-receptor signaling via the mTOR pathway, and, consequently, more synapses. When elevated mTOR signaling was reduced in MHCI-deficient mice, normal synapse density was restored.
Thus, Boulanger said, MHCI and autism-associated genes appear to converge on the mTOR-synapse regulation pathway. This is intriguing given that inflammation during pregnancy, which alters MHCI levels in the fetal brain, may slightly increase the risk of autism in genetically predisposed individuals, she said.
“Up-regulating MHCI is essential for the maternal immune response, but changing MHCI activity in the fetal brain when synaptic connections are being formed could potentially affect synapse density,” Boulanger said.
Ben Barres, a professor of neurobiology, developmental biology and neurology at the Stanford University School of Medicine, said that while it is known that both insulin-receptor signaling increases synapse density, and MHCI signaling decreases it, the researchers are the first to show that MHCI actually affects insulin receptors to control synapse density.
“The idea that there could be a direct interaction between these two signaling systems comes as a great surprise,” said Barres, who was not involved in the research. “This discovery not only will lead to new insight into how brain circuitry develops but to new insight into declining brain function that occurs with aging.”
This section of adult mouse cerebellum shows insulin receptors (green) and calbindin (red), which in this case is present in the cerebellar neurons known as Purkinje cells. Insulin receptors are highly expressed in fibers that form synapses onto Purkinje cells, which express MHCI. Thus both in the cerebellum and hippocampus (previous image), insulin receptors are highly expressed in cells that form synapses onto MHCI-expressing neurons, which suggests MHCI and insulin receptors could interact, either directly or indirectly, in the living brain. (Image courtesy of Lisa Boulanger, Department of Molecular Biology)
Particularly, the research suggests a possible functional connection between type II diabetes and Alzheimer’s disease, Barres said.
“Type II diabetes has recently emerged as a risk factor for Alzheimer’s disease but it has not been clear what the connection is to the synapse loss experienced with Alzheimer’s disease,” he said. “Given that type II diabetes is accompanied by decreased insulin responsiveness, it may be that the MHCI signaling becomes able to overcome normal insulin signaling and contribute to synapse decline in this disease.”
Research during the past 15 years has shown that MHCI lives a prolific double-life in the brain, Boulanger said. The brain is “immune privileged,” meaning the immune system doesn’t respond as rapidly or effectively to perceived threats in the brain. Dozens of studies have shown, however, that MHCI is not only present throughout the healthy brain, but is essential for normal brain development and function, Boulanger said. A 2013 paper from her lab published in the journal Molecular and Cellular Neuroscience showed that MHCI is even present in the fetal-mouse brain, at a stage when the immune system is not yet mature.
“Many people thought that immune molecules like MHCI must be missing from the brain,” Boulanger said. “It turns out that MHCI immune proteins do operate in the brain — they just do something completely different. The dual roles of these proteins in the immune system and nervous system may allow them to mediate both harmful and beneficial interactions between the two systems.”
The paper, MHC Class I Limits Hippocampal Synapse Density by Inhibiting Neuronal Insulin Receptor Signaling, was published Aug. 27 in the Journal of Neuroscience. Boulanger worked with Carolyn Tyler, a postdoctoral research fellow in PNI; Julianna Poole, who received her master’s degree in molecular biology from Princeton in 2014; Princeton senior Joseph Park; and Lawrence Fourgeaud and Tracy Dixon-Salazar, both at UCSD. The work was supported by the Whitehall Foundation; the Sloan Foundation; Cure Autism Now; the Princeton Neuroscience Institute Innovation Fund; the Silvio Varon Chair in Neuroregeneration at UCSD; Autism Speaks; and the National Science Foundation.
See the full article here.
About Princeton: Overview
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As a world-renowned research university, Princeton seeks to achieve the highest levels of distinction in the discovery and transmission of knowledge and understanding. At the same time, Princeton is distinctive among research universities in its commitment to undergraduate teaching.
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<urn:uuid:2b456beb-2e93-457b-800e-fec4d79e4f32> | seed | The second section of DSM-5 is the heart of the system; it contains 23 categories of psychiatric
illness and their diagnostic criteria. For example, these categories include Depressive Disorders
and Related Disorders and Neurodevelopmental Disorders. Within each category of psychiatric illness specific diagnoses and their diagnostic criteria are described. The category under which an illness is listed creates an expectation that the illness is related to the category. For example, in DSM-IV, obsessive compulsive disorder was grouped under the Anxiety Disorders category, which reflected the understanding
of the time that obsessive compulsive disorder was an anxiety disorder. In DSM-5 it is not listed under the category of Anxiety Disorders but is instead now in its own category. It is no longer considered an anxiety disorder.
The category in which an illness is placed can have great influence on clinicians’ efforts to understand and treat a disorder. The warranted assumption is that the listed illness has some possible relationship to the category that it is in as well as to other illnesses listed in the same category. There are at least some shared symptoms between disorders in the same category and the etiology and the treatment of the disorders might be similar.
Examining the DSM-5 category of Depressive Disorders, the first illness discussed is Disruptive Mood Dysregulation Disorder (DMDD) (1). As will be demonstrated, DMDD is not a depressive disorder and listing it as one is a consequential mistake.
Although there are many hedges and exceptions to making the diagnosis of DMDD in DSM-5, the essential criteria are: three temper tantrums per week at a minimum and a persistent irritable mood between tantrums. The tantrums and irritable mood must have lasted for at least one year, and the diagnosis must be apparent by age 10 years. The diagnosis can’t be made before age six years and after age 18 years. The diagnosis can’t be made in children with bipolar disorder. According to the text in DSM-5, the DMDD diagnosis was created to prevent the erroneous diagnosis of bipolar disorder in children with chronic irritability but no symptoms of mania. In children with both DMDD and oppositional defiant disorder (ODD), the DMDD diagnosis is to be given, but ODD is not. In DMDD, irritability between tantrums is present and is more severe than in ODD. Patients with ADHD and patients with depression can be given a diagnosis of DMDD. According to DSM-5, patients whose irritability is only present when the patients are depressed should be given a diagnosis of depression rather than DMDD.
Irritability is not a symptom of depression in adults. Although in children and adolescents it is a permitted depression symptom, it is non-specific and found in most psychiatric disorders. The DSM-5 text explains classifying DMDD as a depressive disorder because of the irritable state between temper tantrums and because irritable children have been reported to grow into depressed adults. Irritability between temper tantrums does not lend any weight to a diagnosis of depression, and irritability in adults is not a permitted depression symptom. Irritability between temper tantrums seems to be a measure of the severity of the patient’s oppositionality rather than a symptom of a new depressive disorder.
This point is underscored in the DSM-5 text in a separate discussion of the diagnosis of major depression in which it is noted that irritability in patients with ADHD should not be counted toward the depression diagnosis unless the irritability only occurs at those times when the child exhibits the usual symptoms of depression (2).
Diagnosing a disorder solely on the basis of speculation about its longitudinal outcome is unprecedented in DSM. Rather, diagnoses in DSM are based on the presence of current, observable, well-defined symptoms.
There are unwelcome clinical consequences of erroneously classifying DMDD as a depressive disorder. First, the diagnosis may lead the clinician to treat the disorder as if it were major depression, with SSRI medications. There is no evidence that these medications are effective for DMDD. Second, the diagnosis may move the focus of treatment away from the patient’s symptoms: irritability and temper tantrums. Based on my clinical experience and having treated many hundreds of children who would meet DMDD criteria, what these children really have is oppositional defiant disorder and, almost always, ADHD. Oppositional defiant disorder and ADHD respond well and safely to behavior modification and stimulant medication.
Placing DMDD in the Depressive Disorders rather than in a Disruptive Behavior category is a disservice to these children and the field.
1.American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. pp. 156-160. Arlington VA. American Psychiatric Association 2013.
2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. p. 167 Arlington VA. American Psychiatric Association 2013.
Copyright Stuart L. Kaplan, MD, 2013
Stuart L. Kaplan, M.D., is the author of Your Child Does Not Have Bipolar Disorder: How Bad Science and Good Public Relations Created the Diagnosis. |
<urn:uuid:718b2ff0-9246-43e6-961e-a1d2b447c675> | seed | The small, diffusible molecule cAMP plays a key signalling role in almost all organisms. In S. cerevisiae, cAMP is synthesized by adenylate cyclase , and hydrolyzed by the phosphodiesterases Pde1p and Pde2p [2,3]. The only function of cAMP in yeast is to activate PKA (Protein Kinase A). A molecule of PKA is a tetramer consisting of two catalytic (C) and two regulatory (R) subunits. Cyclic AMP binds to the R subunit, allowing its dissociation from C, allowing C to become catalytically active. PKA is believed to activate Pde1p , as well as indirectly inhibit the activity of adenylate cyclase . We have created two mathematical models (one simplified and one detailed) in order to better understand the mechanisms of PKA activation. We have also created a model to investigate the complete cAMP pathway.
The PKA models are able to behave appropriately when the cAMP level is altered, giving an increased concentration of free catalytic subunit (see Figure 1). In the wild type complete pathway model a "spike" of cAMP is observed after glucose addition. The cAMP level oscillates before reaching a steady state. The spike has a higher peak in the pde1Δ mutant (see Figure 1).
Figure 1. Species concentrations of the detailed PKA model under low (A) and high (B) cAMP concentration. C: cAMP levels of model mutants. Glucose concentration is increased after five seconds.
The models of PKA activation can reproduce events seen in vivo, but the detailed model also allows for concentrations of intermediates to be predicted. This could give insights into the mechanism by which PKA activation is regulated. The complete pathway model can reproduce phosphodiesterase knockout mutant phenotypes seen in vivo , as well as predicting that the cAMP level oscillates before reaching a steady-state. Further analysis and development of these models should give further insights into the cAMP pathway in yeast. |
<urn:uuid:f144652a-de7e-4bf3-99d7-2c9772b5e5d6> | seed | Our Pancreas Divisum Main Article provides a comprehensive look at the who, what, when and how of Pancreas Divisum
Definition of Pancreas divisum
Pancreas divisum: Pancreas divisum is a common congenital anomaly (an anomaly that is present at birth) of the pancreatic duct(s). The Pancreas is a deep-seated organ located behind the stomach. One of its functions is to produce enzymes that are important for the digestion of food in the intestine. The digestive enzymes, in the form of digestive juice, drain from the pancreas via the pancreatic duct into the duodenum (the upper portion of the small intestine) where they aid in digesting food.
The human embryo starts life with two ducts in the pancreas; the ventral duct and the dorsal duct. In more than 90% of the embryos, the dorsal and the ventral ducts will fuse to form one main pancreatic duct. The main pancreatic duct will join the common bile duct (the duct that drains bile from the gallbladder and the liver) to form a common bile and pancreatic duct which drains into the duodenum through the major papilla. In approximately 10% of embryos, the dorsal and the ventral ducts fail to fuse. Failure of the ventral and the dorsal pancreatic ducts to fuse is called pancreas divisum (because the pancreas is drained by two ducts). In pancreas divisum, the ventral duct drains into the major papilla, while the dorsal duct drains into a separate minor papilla.
The majority of individuals born with pancreas divisum experience no symptoms throughout life, will remain undiagnosed and will not require treatment. A small number of patients with pancreas divisum will experience repeated episodes of pancreatitis. Pancreatitis is an inflammation of the pancreas that can cause severe abdominal pain and more severe complications. Some patients with pancreas divisum may develop chronic abdominal pain without pancreatitis.
Doctors are not certain how pancreas divisum causes abdominal pain and pancreatitis. One theory is that the minor papilla is too narrow to adequately drain the digestive juices in the dorsal duct. The backup of the digestive juices elevates the pressure in the minor duct that causes abdominal pain and pancreatitis.
The most accurate test to diagnose pancreas divisum is ERCP, which can demonstrate the presence of two separately draining pancreatic ducts. However, ERCP itself sometimes can cause attacks of pancreatitis. Other tests that can help diagnose pancreas divisum without the risk of causing pancreatitis include endoscopic ultrasound (EUS), and MRI (magnetic resonance imaging).
Pancreas divisum without symptoms needs no treatment. Treatment of patients with abdominal pain and recurrent pancreatitis attributable to pancreas divisum has not been well established. Some doctors will attempt sphincterotomy (cutting of the minor papilla during ERCP to enlarge its opening). Others will insert a stent during ERCP into the duct to prevent duct blockage. These procedures are not risk free. Therefore, patients with symptomatic pancreas divisum are best evaluated and treated by doctors in centers experienced in treating pancreatic diseases.
Last Editorial Review: 6/14/2012
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<urn:uuid:0a5c2cb9-1c7e-402f-85f1-9fdfee18bc68> | seed | A flatworm known for its ability to regenerate cells is shedding more light on how cancer could be treated and how regenerative medicine could better target diseases, according to researchers at the University of California, Merced.
In research published online in the Journal of Cell Science, biology Professor Néstor Oviedo has shown that signaling by a protein called Target of Rapamycin (TOR) -- found in humans and most other mammals -- is crucial for planaria's unique tissue regeneration. Disabling the protein prevents the flatworm's regrowth, a sign that disabling it in abnormal cells could prevent the growth of a cancer.
"It's a new model in which we can study stem cell behavior by manipulating the signaling pathways," Oviedo said.
Researchers have recognized that the TOR protein plays a role in cancer, aging and degenerative diseases, but they haven't figured out how it works.
Oviedo's lab is approaching this question using tiny flatworms known as planaria. Long relegated as a scientific oddity, the planarian is now among the species that could be crucial in understanding the role of stem cells. The worm's ability to repair itself is unparalleled, and its secrets could help combat cancer and degenerative diseases.
For this study, Oviedo's lab disabled the TOR protein in planaria and then amputated parts of the flatworm. Under typical circumstances, the organism would be able to repair itself.
But researchers discovered the planaria's stem cells recognized they needed to regrow tissue but were unable to regenerate it in the correct place and instead formed tissues in abnormal places. This kind of regeneration hasn't been reported before. Additionally, the planaria with the disabled protein were unable to grow, even if nutrients were available.
In addition to stopping cancer, understanding TOR and its role in regulation could lead to the development of medicines to encourage tissue regeneration and to fight degenerative diseases, such as Alzheimer's.
Graduate student Harshani Peiris, who was the lead author on the paper, said the planaria gives researchers the ability to look at the reactions of an entire organism, rather than just looking at cells in a Petri dish.
"We have a cutting-edge look into what's happening at the system level," Peiris said.
The research was funded by a grant from the UC Cancer Research Coordinating Committee.
The paper's coauthors include undergraduate students Daniel Ramirez and Devon Davidian, Professor Marcos Garcia-Ojeda, and staff members Elyze Ozamoto and Frank Weckerle.
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<urn:uuid:5ff69850-6e5c-455f-aff2-daa3464eb5c3> | seed | Items in AFP with MESH term: Atrial Fibrillation
National Stroke Association Develops a Consensus Statement on Prevention of Stroke - Special Medical Reports
ABSTRACT: Atrial fibrillation is the most common cardiac arrhythmia. It impairs cardiac function and increases the risk of stroke. The incidence of atrial fibrillation increases with age. Key treatment issues include deciding when to restore normal sinus rhythm, when to control rate only, and how to prevent thromboembolism. Rate control is the preferred management option in most patients. Rhythm control is an option for patients in whom rate control cannot be achieved or who have persistent symptoms despite rate control. The current recommendation for strict rate control is a resting heart rate of less than 80 beats per minute. However, one study has shown that more lenient rate control of less than 110 beats per minute while at rest was not inferior to strict rate control in preventing cardiac death, heart failure, stroke, and life-threatening arrhythmias. Anticoagulation therapy is needed with rate control and rhythm control to prevent stroke. Warfarin is superior to aspirin and clopidogrel in preventing stroke despite its narrow therapeutic range and increased risk of bleeding. Tools that predict the risk of stroke (e.g., CHADS2) and the risk of bleeding (e.g., Outpatient Bleeding Risk Index) are helpful in making decisions about anticoagulation therapy. Surgical options for atrial fibrillation include disruption of abnormal conduction pathways in the atria, and obliteration of the left atrial appendage. Catheter ablation is an option for restoring normal sinus rhythm in patients with paroxysmal atrial fibrillation and normal left atrial size. Referral to a cardiologist is warranted in patients who have complex cardiac disease; who are symptomatic on or unable to tolerate pharmacologic rate control; or who may be candidates for ablation or surgical interventions.
Update on Subclinical Hyperthyroidism - Article
ABSTRACT: Subclinical hyperthyroidism is defined by low or undetectable serum thyroid-stimulating hormone levels, with normal free thyroxine and total or free triiodothyronine levels. It can be caused by increased endogenous production of thyroid hormone (as in Graves disease or toxic nodular goiter), administration of thyroid hormone for treatment of malignant thyroid disease, or unintentional excessive thyroid hormone therapy. The rate of progression to overt hyperthyroidism is higher in persons who have suppressed thyroid-stimulating hormone levels compared with those who have low but detectable levels. Subclinical hyperthyroidism is associated with an increased risk of atrial fibrillation in older adults, and with decreased bone mineral density in postmenopausal women; however, the effectiveness of treatment in preventing these conditions is unknown. There is lesser-quality evidence suggesting an association between subclinical hyperthyroidism and other cardiovascular effects, including increased heart rate and left ventricular mass, and increased bone turnover markers. Possible associations between subclinical hyperthyroidism and quality of life parameters, cognition, and increased mortality rates are controversial. Prospective randomized con- trolled trials are needed to address the effects of early treatment on potential morbidities to help determine whether screening should be recommended in the asymptomatic general population.
Evaluation of Asymptomatic Atrial Fibrillation - FPIN's Clinical Inquiries
ABSTRACT: The American College of Chest Physicians provides recommendations for the use of anticoagulant medications for several indications that are important in the primary care setting. Warfarin, a vitamin K antagonist, is recommended for the treatment of venous thromboembolism and for the prevention of stroke in persons with atrial fibrillation, atrial flutter, or valvular heart disease. When warfarin therapy is initiated for venous thromboembolism, it should be given the first day, along with a heparin product or fondaparinux. The heparin product or fondaparinux should be continued for at least five days and until the patient’s international normalized ratio is at least 2.0 for two consecutive days. The international normalized ratio goal and duration of treatment with warfarin vary depending on indication and risk. Warfarin therapy should be stopped five days before major surgery and restarted 12 to 24 hours postoperatively. Bridging with low-molecular-weight heparin or other agents is based on balancing the risk of thromboembolism with the risk of bleeding. Increasingly, self-testing is an option for selected patients on warfarin therapy. The ninth edition of the American College of Chest Physicians guidelines, published in 2012, includes a discussion of anticoagulants that have gained approval from the U.S. Food and Drug Administration since publication of the eighth edition in 2008. Dabigatran and apixaban are indicated for the prevention of systemic embolism and stroke in persons with nonvalvular atrial fibrillation. Rivaroxaban is indicated for the prevention of deep venous thrombosis in patients undergoing knee or hip replacement surgery, for treatment of deep venous thrombosis and pulmonary embolism, for reducing the risk of recurrent deep venous thrombosis and pulmonary embolism after initial treatment, and for prevention of systemic embolism in patients with nonvalvular atrial fibrillation. |
<urn:uuid:162a5e6b-15cd-40fe-b63f-373b6d6614c3> | seed | Am Fam Physician. 2004 Jan 15;69(2):413-414.
Of all the gynecologic cancers, ovarian cancer is the most common cause of mortality. More than 60 percent of patients with ovarian cancer do not present until they are at an advanced stage, and the average five-year survival rate is reported to be lower than 20 percent. Tingulstad and colleagues analyzed data on ovarian cancer in Norwegian women to identify factors that could distinguish women with the best prognosis for survival.
They studied records of 571 verified ovarian cancer cases in a Norwegian region and excluded patients who did not have laparotomy or had a doubtful diagnosis. They found that the incidence of around 12 cases per 100,000 increased with age up to 60 to 69 years. The follow-up time ranged from 60 to 178 months, with a median of 106 months. The crude five-year survival was around 40 percent, and the median survival was 32 months. In the initial statistical analysis, the significant predictors of death within five years were older age, higher International Federation of Gynecology and Obstetrics (FIGO) stage, and larger residual tumor after surgery. The hazard ratio in women older than 75 years was 2.8 times that in women younger than 45 years. Although ovarian cancer was relatively uncommon in women younger than 45 years, 71 percent were alive at five years compared with only 18 percent of women 75 years or older. Similarly, the hazard ratio for more than 1 cm of residual tumor was 1.72 times that for residual tumor of up to 1 cm. Only 9 percent of patients with more than 1 cm of residual tumor were alive at five years compared with 61 percent of those with more complete removal. The strongest risk factor was the FIGO stage of the tumor. The hazard ratio for stage IV was 11.75 times that of stage I. For FIGO stage I, the five-year survival was 86 percent compared with 11 percent for stage IV. Other variables, such as comorbidity, tumor histology, or CA125 level, were not significant in predicting five-year survival.
The authors believe these data can be applied to treatment and to counseling patients and families about prognosis. The significance of residual tumor should stimulate surgeons to maximize tumor removal. Although the results confirm the importance of detection at an earlier FIGO stage, effective screening for ovarian cancer has not been developed.
Tingulstad S, et al. Survival and prognostic factors in patients with ovarian cancer. Obstet Gynecol. May 2003; 101:885–91.
editor's note: Reports like this can be powerful tools in supporting the patient and her family through this devastating illness. First, ovarian cancer is not an immediate death sentence: the five-year survival rate has risen to nearly 40 percent. More importantly, one can look more closely at the subgroups and give patients much more specific information. For some patients, this will be cautious hope, as the five-year survival rates in some subgroups were more than 70 percent. For other patients, it provides a more realistic estimate of the seriousness and likely progression of the disease. Most families assume a painful death is imminent. We owe it to them to provide the best estimates of survival, to ensure the best possible care, and above all, to be available and reliable as they go through the process.—A.D.W.
Copyright © 2004 by the American Academy of Family Physicians.
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<urn:uuid:f5b1e967-8639-4c06-a471-561ed65a386b> | seed | This release is available in German.
New research explains how cells regulate their bonds during the development of new blood vessels. For the first time, the role of the protein Raf-1 in determining the strength of the bond between cells has been shown. Manuela Baccarini's group at the Max F. Perutz Laboratories, a joint venture of the University of Vienna and the Medical University of Vienna, shows if Raf-1 is not present, the cells cannot stick together and the formation of new blood vessels is inhibited. This discovery may one day lead to new approaches to cancer treatment.
Angiogenic sprouting, the process by which new blood vessels grow from existing vessels, is a double-edged sword. It enables the cardiovascular system to develop in the embryo, and is vital for tissue regeneration in adults. But it also supplies growing tumors with nutrients and oxygen.
Angiogenesis is an example of collective cellular migration. Cells move as a group, held together by connections called adherens junctions. For the cells to move, they have to make and break these connections continuously. If the junctions are too stiff, they will not be able to move at all, but if they are too weak, the groups of cells will break apart. How this mechanism is controlled was unknown.
The mechanism has now been uncovered by Manuela Baccarini's group at the Max F. Perutz Laboratories, a joint venture of the University of Vienna and the Medical University of Vienna, who investigate cell signaling. They have established a crucial role for Raf-1, a multi-purpose signal transducer, in this process.
"The real breakthrough came when we were able to use video microscopy on the developing vessels in vitro," explains the paper's first author Reiner Wimmer. "We realized that the cells without Raf-1 were actively migrating, but only as single cells. They could not migrate in a group."
The meaning of this discovery became clear in further experiments: the role of Raf-1 is to bring the new adherens junctions a kinase they need for the remodeling of the cytoskeleton. This means that Raf-1 is fine-tuning the bonds between the migrating cells by causing the local remodeling of the cell's cytoskeleton.
As the process of angiogenic sprouting is necessary for the growth of tumors, this new discovery may one day be applied to produce cancer therapies to target Raf-1 and the other parts of this control mechanism, thereby disrupting the environment of the tumor.
Wimmer R, Cseh B, Maier B, Scherrer K, Baccarini M (2011). Angiogenic sprouting requires the fine-tuning of endothelial cell cohesion by the Raf-1/Rok-α complex. Developmental Cell.
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system. |
<urn:uuid:b896394c-d636-4a11-82e2-46f71f83e5e0> | seed | In order to understand the genetics of Alzheimer's disease (AD), it is first necessary to understand the basics of genetics. Most cells of the body have 46 chromosomes, grouped into 23 pairs. One member of each chromosome pair is transferred from parent to child during fertilization. These chromosomes are composed of deoxyribonucleic acid (DNA), which is the genetic material. Segments or sequences of DNA consist of genes, which encode many of the characteristics of each individual, including hair and eye color. Often, the variation between individuals in these traits is due to variation in the sequence of the DNA of these genes.
Many studies have been carried out to identify the factors associated with an increased risk for developing AD. Initial studies focused on those families in which members developed AD at an early age, typically under the age of 60 years. While these early-onset families comprise less than 5% of all cases of AD, they have provided important information about the genetics of AD. Changes in the DNA sequence (termed mutations) in three different genes have been found to cause AD in some of these families. These genes are called amyloid precursor protein (APP), presenilin 1 (PS1) and presenilin 2 (PS2).
The vast majority of cases of AD have an onset after the age of 60 years. These later-onset cases of AD are less likely to have a mutation in the sequence of the APP, PS1, or PS2 genes. Rather, individuals who develop AD later in life are more likely to have developed the disease due to a combination of environmental and genetic risk factors. A gene, termed apolipoprotein E (ApoE), has been found to be an important risk factor for later onset AD.
The APP, PS1, and PS2 genes are all considered to be causative genes that, when their DNA segments are altered, can cause AD. An important distinction must be made with ApoE. Variation in the DNA sequence of ApoE can increase or decrease the risk that an individual will develop AD; however, it is thought that variation in ApoE alone does not determine whether an individual will develop AD. Therefore, ApoE is often called a susceptibility factor.
It is clear that other genes must also play an important role in affected AD susceptibility. Studies using samples collected and distributed by the National Cell Repository for Alzheimer's Disease will help scientists identify the other important genes contributing to AD susceptibility.
For more information about genetics, please see the Alzheimer's Disease Genetics Fact Sheet from the Alzheimer’s Disease Education & Referral Center (ADEAR) website. |
<urn:uuid:c096b429-1cb4-485c-b6d9-5631dd180590> | seed | Human Embryonic Stem (ES) Cells
In other pages, I describe:
The techniques used in the early steps of each process have been achieved with human cells.
Thirteen years ago a research team led by James Thomson of the University of Wisconsin reported (in the 6 November 1998 issue of Science) that they were able to grow human embryonic stem (ES) cells in culture.
At the time of implantation, the mammalian embryo is a blastocyst.
It consists of the
- trophoblast — a hollow sphere of cells that will go on to implant in the uterus and develop into the placenta and umbilical cord.
- inner cell mass (ICM) that will develop into the baby as well as the extraembryonic amnion and yolk sac.
The cells of the inner cell mass are considered pluripotent; that is, each is capable of producing descendants representing all of the hundreds of differentiated cell types in the newborn baby, including
- Remove the trophoblast cells from a human blastocyst (these were extras not needed for assisted reproductive technology).
- Separate the cells of the inner cell mass and culture them on a plate of "feeder" cells (mouse fibroblasts were used).
- Isolate single cells and grow them as clones.
- Test the clones.
- Each successful clone maintained a normal human karyotype (unlike most cultured human cells — HeLa cells, for example).
- These cells had high levels of the enzyme telomerase, which maintains normal chromosome length and is characteristic of cells with unlimited potential to divide ("immortal").
- When injected into SCID mice, these cells formed teratomas; tumors containing a mix of differentiated human cell types, including cells characteristic of
SCID = severe combined immunodeficiency. |
SCID mice lack a functioning immune system (have neither T cells nor B cells) and so cannot reject foreign tissue. (Some rare inherited diseases of humans are also called SCID. They produce a similar phenotype but involve different molecular defects. [Links])
Human embryonic stem cells have the potential to
- teach us about the process of human embryonic development, its genetic control, etc.
- provide a source of replacement cells to repair damaged human tissue.
As the proper signals are discovered, it will be possible to cause these cells to differentiate along a particular pathway, e.g., to form insulin-secreting beta cells of the islets of Langerhans.
Such cells might be able to replace lost or non-functioning cells in a human patient (e.g., with Type 1 diabetes mellitus).
However, there are problems that remain to be solved before this hope can be realized.
- Production of human ES cells requires the destruction of the blastocyst, and this is morally-repugnant to many people. [Link to a discussion of ways to avoid this difficulty.]
- Cell replacement therapy had better be "patient-specific"; that is, the donated cells should be genetically identical to the recipient. Otherwise, the replaced cells are at risk of being rejected by the host's immune system. [Link to a discussion of "therapeutic cloning" — a method to avoid this.
- ES cells are pluripotent and might differentiate in unwanted ways when introduced into the patient. [Link to ways to use "adult" stem cells instead.]
12 February 2011 |
<urn:uuid:dac9e72f-2d8a-4ea6-aea8-d1a22fd9c684> | seed | Thrombotic thrombocytopenic purpura (TTP) can be fatal or cause lasting damage, such as brain damage or a stroke, if it's not treated right away.
In most cases, TTP occurs suddenly and lasts for days or weeks, but it can go on for months. Relapses (flareups) can occur in up to 60 percent of people who have acquired TTP. Flareups also occur in most people who have inherited TTP.
Plasma treatments are the most common way to treat TTP. Other treatments include medicines and surgery. Treatments are done in a hospital.
Plasma is the liquid part of your blood. It carries blood cells, hormones, enzymes, and nutrients to your body.
TTP is treated with plasma therapy. This includes:
- Fresh frozen plasma for people who have inherited TTP
- Plasma exchange for people who have acquired TTP
Plasma therapy is started in the hospital as soon as TTP is diagnosed or suspected.
For inherited TTP, fresh frozen plasma is given through an intravenous (IV) line inserted into a vein. This is done to replace the missing or changed ADAMTS13 enzyme.
Plasma exchange (also called plasmapheresis) is used to treat acquired TTP. This is a lifesaving procedure. It removes antibodies (proteins) from the blood that damage your ADAMTS13 enzyme. Plasma exchange also replaces the ADAMTS13 enzyme.
If plasma exchange isn't available, you may be given fresh frozen plasma until it is available.
During plasma exchange, an IV needle or tube is placed in a vein in your arm to remove blood. The blood goes through a cell separator, which removes plasma from the blood. The nonplasma part of the blood is saved, and donated plasma is added to it.
Then, the blood is put back into you through an IV line inserted into one of your blood vessels. The time required to complete the procedure varies, but it often takes about 2 hours.
Treatments of fresh frozen plasma or plasma exchange usually continue until your blood tests results and signs and symptoms improve. This can take days or weeks, depending on your condition. You'll stay in the hospital while you recover.
Some people who recover from TTP have flareups. This can happen in the hospital or after you go home. If you have a flareup, your doctor will restart plasma therapy.
Other treatments are used if plasma therapy doesn't work well or if flareups occur often.
For acquired TTP, medicines can slow or stop antibodies to the ADAMTS13 enzyme from forming. Medicines used to treat TTP include glucocorticoids, vincristine, rituximab, and cyclosporine A.
Sometimes surgery to remove the spleen (an organ in the abdomen) is needed. This is because cells in the spleen make the antibodies that block ADAMTS13 enzyme activity. |
<urn:uuid:81097e9f-0ff1-4b7a-8d71-cab192e6cca3> | seed | A treatment for polycystic kidney disease(PKD), a leading cause of fatal kidney failure worldwide, has been identified by a research// team led by Yale biochemist Craig Crews, according to a report in the Proceedings of the National Academy of Sciences.
Over 12 million people worldwide suffer from PKD, a genetic disorder that causes uncontrolled growth of cells lining tubules in the kidneys, and results in the formation of many, large fluid-filled cysts in the kidneys.
“Unfortunately, aside from kidney transplantation, there has been no cure for PKD, nor has there been a suitable drug treatment to slow its progression,” said Crews, associate professor of chemistry, molecular, cellular & developmental biology and pharmacology. “We hope that is about to change,” he said.
The mesh of Traditional Chinese Medicines (TCMs), current advances in chemistry and fundamental processes of developmental biology and health are a research focus for Crews. According to him, a roadblock in the path to TCMs as a source for new medical treatments is lack of understanding the biology and chemistry of how they work.
Triptolide is a potent, biologically active compound isolated from the medicinal ‘Thunder God Vine’ Tripterygium wilfordii Hook F. The TCM tea Lei Gong Teng made from this plant has been used for centuries, as a therapeutic against cancer, inflammation, and auto-immune diseases. Crews and colleagues showed that triptolide causes cell growth arrest in certain cell types.
Normal kidney tubule cells have a built in switch for regulating their growth — two proteins, PKD1 and PKD2, located on a bristle-like cilium that bends in response to fluid flow across the cell. During kidney development, cells destined to line a kidney tubule grow and divide until the tubule is formed, as sensed by fluid flow in the tubule. Fluid flow bends the primary cilium, giving a signal to stop cell growth. PKD is caused by a mutation in the PPage: 1 2 Related medicine news :1
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. The Potential Of Cadaver Transplantation Programme In India5
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<urn:uuid:56fb5925-8eb8-4875-9856-338d9abd4b18> | seed | Notifiable disease surveillance in the United States is predominantly a passive process that is often limited by poor timeliness and low sensitivity. Interoperable tools are needed that interact more seamlessly with existing clinical and laboratory data to improve notifiable disease surveillance.
The Public Health Surveillance Knowledgebase (PHSkb™) is a computer database designed to provide quick, easy access to domain knowledge regarding notifiable diseases and conditions in the United States. The database was developed using Protégé ontology and knowledgebase editing software. Data regarding the notifiable disease domain were collected via a comprehensive review of state health department websites and integrated with other information used to support the National Notifiable Diseases Surveillance System (NNDSS). Domain concepts were harmonized, wherever possible, to existing vocabulary standards. The knowledgebase can be used: 1) as the basis for a controlled vocabulary of reportable conditions needed for data aggregation in public health surveillance systems; 2) to provide queriable domain knowledge for public health surveillance partners; 3) to facilitate more automated case detection and surveillance decision support as a reusable component in an architecture for intelligent clinical, laboratory, and public health surveillance information systems.
The PHSkb provides an extensible, interoperable system architecture component to support notifiable disease surveillance. Further development and testing of this resource is needed.
In the United States, notifiable disease reporting is mandated by state and local regulations. These regulations require medical providers and laboratories to notify state and local public health authorities of persons diagnosed with a reportable condition . A reportable condition is one for which regular, frequent, and timely information regarding individual cases is considered necessary for the prevention and control of the disease. Each state determines which conditions are reportable within its jurisdiction. The Council of State and Territorial Epidemiologists (CSTE) determines which diseases all states will voluntarily report nationally to the federal Centers for Disease Control and Prevention (CDC) . Each year, CDC publishes a summary of notifiable disease activity in the United States .
Surveillance case definitions provide uniform criteria for reporting notifiable diseases. Case definitions for nationally notifiable diseases have previously been published in printed copy and are currently maintained on the CDC website . The format of case definitions varies somewhat by condition but often contains information on clinical criteria, laboratory criteria, case classification categories, and criteria for classification. The case definitions are written in text to provide guidance to health providers and surveillance epidemiologists when determining whether or not an individual case meets the criteria for reporting. The case definitions are not derived from a formalized information model and are typically not developed for computational purposes. Their content, however, includes numerous terms found in standard medical vocabularies.
Routine notifiable disease surveillance often suffers from incomplete reporting and poor timeliness [7,8]. New threats of bioterrorism have resulted in increased pressures to improve the sensitivity and timeliness of routine disease surveillance, particularly through the use of improved electronic data interchange. Pilot studies have demonstrated improved surveillance sensitivity and timeliness through electronic reporting of laboratory findings by laboratories to public health agencies [9,10]. Other electronic data (e.g., coded discharge diagnoses or pharmacy dispensing data) have also been used to improve the sensitivity and timeliness of routine notifiable disease surveillance [11,12]. Implementation of these methods often depends on the existence of tables that relate the coded laboratory or clinical findings to the notifiable conditions under surveillance. The systematized nomenclature of medicine (SNOMED) and logical observation identifier names and codes (LOINC) have been identified as important vocabulary standards for constructing these tables .
Previous efforts to separately maintain information regarding the diseases that are reportable, the content of case definitions, and mapping tables of coded observations to notifiable diseases, have resulted in a proliferation of disparate, unintegrated spread sheets and documents that are used to support notifiable disease surveillance activities. In 2003, we began to develop a database to integrate these information sources – the Public Health Surveillance knowledgebase (PHSkb™). The long-term goal of the PHSkb is to provide a resource to improve the sensitivity, timeliness, and quality of surveillance data through improved electronic data interchange. To achieve this goal, the notifiable disease domain is expressed by using methods of ontology development and knowledge representation, combined with integration of national vocabulary standards that cover the domain. Whereas these methods of ontology development and knowledge representation have been applied to health information retrieval, clinical information systems, and clinical decision support, their application to public health disease surveillance systems is less established. This paper describes the initial creation of the PHSkb. Further field testing will be needed, however, to determine the impact of such methods on surveillance sensitivity, timeliness, and data quality.
Construction and content
The knowledgebase scope includes diseases, conditions, or other events that are reportable in one or more reporting jurisdictions in the United States. The reporting jurisdictions (n = 52) are those states or cities that report data weekly to CDC via the National Notifiable Diseases Surveillance System (NNDSS), which includes the 50 U.S. states, New York City, and the District of Columbia. Reportable conditions in each jurisdiction were ascertained from the health department website for each jurisdiction [see 1].
While all jurisdictions provided a list of reportable conditions on their website, in many instances this information was not prominently displayed and required substantial effort to identify. The median time interval needed to identify reporting requirements by navigating the website was approximately one minute, ranging from less than 15 seconds to more than eight minutes. Identifying requirements often required understanding of the organizational structure of the agency and knowledge of which bureau or division was responsible for posting such information to the website. During a 6-month interval between the time the data were first collected and later reconfirmed, 16 (31%) of 52 jurisdictions had updated or otherwise modified their reportable conditions list, suggesting a dynamic information domain.
A knowledge representation model was created for the notifiable disease domain (Figure 1) that depicts the major root concepts in the ontology, their attributes, and relationships between concepts. By necessity, the figure is an oversimplification and does not account for the full hierarchical classification of concepts within the knowledgebase, or identify all the links between concepts. The reader is referred to the PHSkb for the full knowledge representation.
Figure 1. Knowledge representation model of notifiable condition domain.
Notifiable conditions include not only single instances of disease, but also infectious agents, substances, procedures, and findings. Reportable findings can include individual findings (e.g., a disease carrier state) or population findings (e.g., an outbreak or cluster of illness). Reportable procedures include concepts such as the administration of medications or prophylaxis specific for a particular disease. Reportable infectious agents include those microbial isolates which laboratories are required to report, independent of clinical illness. For reportable diseases, 18 sub-categories of disease were identified among jurisdiction reporting requirements. However, the majority of reportable diseases fall within the category of infectious disease. For this category, additional attribute knowledge was included, such as the causative agent, insect vector, and associated immunoprophylaxis.
Additional root classes were included for the jurisdictions where events are reportable, and the various terminology standards that cover the domain. Information specified in the surveillance case definition was included as attribute data for each disease and is described in more detail in the content section below.
Instances of the major classes were classified hierarchically, focusing initially on the disease class. The infectious agent, vector, and substance classes were constructed by including all organisms or substances with a causal or other obvious association to concepts in the reportable disease class. Semantic heterogeneity of notifiable events between different reporting jurisdictions was resolved by harmonizing term variants to a standard concept when possible. SNOMED CT (release 1/2003, with the Clue browser) was used extensively to construct the class hierarchy and to harmonize term variations between jurisdictions . In some instances, individual jurisdiction or national data aggregation needs required modification or extension of the concept hierarchy in SNOMED CT. The full list of reportable diseases (n = 373), infectious agents (n = 174), substances (n = 48), findings (n = 58), and procedures (n = 3) is presented in this report along with the number of jurisdictions in which each event is reportable [see 2 thru 6]. The number of jurisdictions should be interpreted with caution, however, because a particular reportable event might be referred to as a broader or more narrowed concept in another jurisdiction. Furthermore, the reportable condition lists available on the jurisdiction websites, at the time of data collection, might not be the most current reporting requirements given to health providers. The tables are intended to provide a quick glimpse of the breadth of the notifiable condition domain; however, further work is needed to validate the information contained in the knowledgebase with state surveillance partners.
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Additional concepts, not reportable in any jurisdiction, were included in the PHSkb to construct the hierarchy for each root class. In the disease class, for example, additional concepts were added either because the condition is a parent-level concept in the class hierarchy under which a reportable disease exists, or the condition is a clinical sub form with distinct clinical symptoms and findings and is already represented by a broader parent concept that is notifiable (i.e., pneumonic and bubonic plague are clinical forms of the notifiable disease plague). More than 570 additional concepts were added to the knowledgebase to construct the class hierarchies.
Content and relation to vocabulary standards
Concepts in the class hierarchies were mapped to SNOMED-CT and summary results are presented for events reportable in at least one jurisdiction (Table 1). In general, SNOMED-CT provides extensive domain coverage, particularly for the reportable diseases, infectious agents, and substances. Reportable population findings (e.g. disease outbreaks) are not covered as thoroughly in SNOMED. Concepts in the disease class were further mapped to other vocabulary standards. Approximately 76% of concepts in the disease class were in ICD-9 and 48% in ICD-10; 77% had a UMLS concept unique identifier (CUI). Therefore, SNOMED-CT provided better domain coverage than these other coding standards. For the jurisdiction class, Federal Information Processing Standards (FIPS) codes were used to identify each jurisdiction .
Table 1. Domain content coverage of reportable events with SNOMED CT.
Additional attribute data for each class instance were then entered into the database. When a reportable disease, infectious agent, or substance has been identified as a possible bioterrorism agent or condition the category of BT agent (A, B, or C) was specified in the knowledgebase. Knowledge pertaining to the disease class is the most fully developed in the PHSkb. It contains data on whether or not the disease is nationally notifiable, the year it first became notifiable, and the CDC-assigned code used by jurisdictions to report cases to CDC. For each infectious disease, the associated infectious agents, insect vectors, and incubation periods were identified (when not obvious) either from the surveillance case definition or from the Control of Communicable Diseases Manual . Associated immunoprophylaxes were coded by using the CVX-Vaccines Administered codes developed by CDC for use in immunization registries and adopted by HL7 as a standard code set . Approximately 100 CVX-coded vaccines were associated with 68 reportable diseases in the knowledgebase. The surveillance case definition text was used to populate the clinical and laboratory criteria . Terms from the case definition were parsed and mapped to SNOMED-CT concepts to populate the symptoms & findings, associated procedure, and associated medication slots. A total of 344 findings, 46 procedures, and 19 medications from SNOMED-CT were mapped to terms included in, or implied by, the case definition text.
Finally, the existing table created to support electronic laboratory reporting, that relates LOINC coded laboratory tests to notifiable diseases was imported into the database and used to populate the associated laboratory test field for each disease. We did not attempt to precisely map the laboratory criteria from case definitions to LOINC. Experience has demonstrated that fully specified LOINC terms are often substantially more granular than criteria specified in surveillance case definitions. In addition, the lack of a hierarchical representation within LOINC causes mapping to the less granular case definition criteria to be difficult . However, more that 3,500 LOINC codes have direct relevance as diagnostic tests for reportable diseases and are included in the knowledgebase.
The model was instantiated by using the Protégé-2000 ontology and knowledgebase editing software (version 1.9). Protégé is an open-source, Java tool that provides an extensible architecture for creating customized knowledge-based applications. Multiple plug-ins have been developed to extend the functionality of Protégé, including various inference and reasoning tools. We used JESS (Java Expert System Shell) tab plug-in (version 1.1) to query the PHSkb.
The PHSkb has at least three potential uses: 1) providing a framework for the development and maintenance of a controlled vocabulary for reportable events of public health importance; 2) providing convenient, queriable domain knowledge to surveillance epidemiologists, data reporters, and others; and 3) providing a reusable domain knowledge component for intelligent surveillance information system architectures. Each of these broad areas of utility is discussed further in this report.
Development and maintenance of a controlled vocabulary for reportable conditions
To support the activities of the NNDSS, CDC maintains an authoritative code set for use when jurisdictions report notifiable diseases to CDC. This code set is maintained as a spreadsheet and distributed annually to states when changes occur . This authoritative code set is not concept-based, does not express hierarchical relationships between terms, and focuses predominantly on those conditions that are nationally notifiable.
Our review of the jurisdiction specific websites [see 1] identified extensive semantic heterogeneity between jurisdictions when referring to reportable conditions, particularly for those conditions that are not nationally notifiable. Conditions reported locally within a jurisdiction that are not nationally notifiable are usually assigned a code by each jurisdiction for use within their system. Without a hierarchical representation, it is difficult to aggregate data across multiple jurisdictions for these diseases, because different jurisdictions use different levels of granularity when defining their own disease reporting requirements. Therefore, aggregation across jurisdictions requires extensive mapping and harmonization of jurisdiction-specific extensions to the code set for notifiable conditions. Having the notifiable disease domain organized across jurisdictions in a hierarchical classification will facilitate data aggregation and electronic data interchange across jurisdictions and between parties within jurisdictions.
CDC-assigned reportable disease codes exist for approximately 128 (34%) of the 373 diseases reportable in at least one jurisdiction. For the remaining diseases reportable in at least one jurisdiction but without a standard name or code (i.e. non-nationally notifiable), non-standard codes are assigned by each jurisdiction, making cross jurisdiction data aggregation difficult or impossible and resulting in a fragmented national surveillance approach. The PHSkb attempts to move from an authoritative code set characterized by incomplete domain coverage to managing the notifiable condition domain as a controlled vocabulary. When fully implemented, features of PHSkb would include harmonizing term variants across jurisdictions, assigning nationally standard codes for locally reportable events, expressing the hierarchical relation between notifiable conditions, and maintaining mappings between notifiable conditions and concept equivalents within other widely used coding standards.
Queriable domain knowledge
The PHSkb provides convenient, queriable domain knowledge for surveillance epidemiologists and other public health partners. The Protégé software has a built-in query development utility that allows users to construct standard queries and save them to a query library. Several standard queries of the PHSkb have been created and saved in the query library. Examples of such queries include the following.
• In what jurisdictions is a particular disease notifiable?
• What are the reportable conditions in a particular jurisdiction?
• What disease is caused by a particular microorganism?
• What diseases have a particular constellation of symptoms mentioned in their surveillance case definition?
• What diseases are transmitted by a particular insect vector?
• What diseases are associated with a particular laboratory test or finding?
In addition, custom queries can be developed using the inference tools in Protégé (e.g., the JESS tab).
A web interface to the PHSkb is needed to provide broad, web-based, public access to the query functions of the knowledgebase. In the interim, while the web interface is being developed, we have received numerous queries as part of our oversight responsibilities for the NNDSS and have used the PHSkb to respond directly to these domain-specific queries. If adequate, ongoing maintenance of the PHSkb exists, the effort needed to access jurisdiction specific requirements will be reduced by the availability of a central, queriable knowledgebase integrating domain information derived from > 50 different agencies. Such an integrated, centrally-accessed database could be particularly useful to data providers who report to multiple jurisdictions (e.g., large reference laboratories or regional and national provider networks serving communities in different states).
Reusable architecture component
The PHSkb can function as a reusable component in an architecture for intelligent public health surveillance and clinical information systems . Private software developers have referenced the reporting requirements specified in the PHSkb when developing public health surveillance information systems, and it has been embedded in the architecture of at least one state-based system under development . For users of this state web-based system, the class hierarchies could be navigated and related knowledge could be viewed within the system. When a particular disease was selected for reporting, the system was able to query the knowledgebase and dynamic data entry screens were generated, based on its content. In this way, domain knowledge can be maintained separately by subject matter experts without requiring extensive hard-coding changes to the surveillance software resulting from emerging public health threats or rapidly evolving domain knowledge for a particular disease.
The PHSkb could also be used as an inference engine to identify reportable events from one or more observations. Previous studies have demonstrated that knowledge-based patient screening methods can lead to earlier diagnosis of rare infections, thus improving both clinical patient management and disease surveillance . Two-dimensional tables are currently used to infer cases of reportable disease from LOINC-coded laboratory test observations. In the future, the PHSkb might be able to provide more robust inference capability by integrating 1) laboratory observations with clinical findings and exposure criteria, 2) a hierarchical class structure, and 3) information on jurisdiction-specific requirements. Future development might also address the logic contained in case definitions. Before additional extensions are included, however, further testing is needed regarding the current inference capability of the PHSkb when interacting with laboratory and clinical data streams.
The historical paradigm of notifiable disease surveillance is based on passive reporting of notifiable events from health-care providers to public health agencies. This paradigm relies on public health agencies informing providers of what should be reported (i.e., reportable disease list), a common understanding of the case reporting criteria (i.e., surveillance case definition) and a method for sending and receiving the reports (i.e. telephone hotline, fax, mailed morbidity reports, or web-based reports). Given that there is often minimal reward for reporting or punitive consequences for not reporting, it is not surprising that this passive, unautomated surveillance paradigm often results in poor surveillance sensitivity and timeliness. The information technology and internet revolution during the previous decade has created new opportunities to alter this paradigm and use pre-existing electronic health data to improve the sensitivity and timeliness of surveillance data while reducing the reporting burden on individual providers.
In the same way that clinical practice guidelines have been implemented into rule-based expert systems featuring clinical decision support, the surveillance case definitions provide a basis for developing a rules-based decision support capability for the public health surveillance function . Reusable, extensible domain knowledge components such as the PHSkb are a necessary, but not sufficient, component for fulfilling the paradigm shift from passive disease reporting to efficient, comprehensive, automated electronic data interchange.
Multiple barriers remain, however, for achieving this paradigm shift. First, current reportable disease requirements are unnecessarily fragmented by jurisdiction. The current variability between states regarding reporting requirements makes it cumbersome to develop tools that are generalizable across jurisdictions to assist providers in meeting local reporting requirements. Second, current surveillance case definitions are not based on a uniform information model, are not written for automated interpretation, and often contain ambiguous or conflicting logic. Efforts to retrofit existing case definitions to a standard information model are necessarily awkward and difficult. However, the current definitions do represent an important starting point for standard public health surveillance guidelines, analogous to clinical practice guidelines that often require months or years of consensus-building to create. Third, the use of electronic medical records (EMR) is still not widespread and the cost of implementing EMRs is often a barrier. Finally, more robust clinical vocabulary standards such as SNOMED-CT are not yet widely used in health-care settings. In addition, much of the clinical information contained in patient charts is text that is not electronic and not coded to any vocabulary standard. Further advances are needed in the area of natural language processing and automated methods for converting text data to electronic vocabulary standards.
Despite these important barriers, reusable domain knowledge components such as the PHSkb hold promise for improved interoperability between surveillance information systems and their clinical and laboratory counterparts, through use of a set of integrated content standards for disease surveillance. Field testing of the PHSkb is needed, however, to determine its impact on surveillance metrics such as sensitivity, timeliness, and data quality. Future development of the PHSkb should focus on 1) validating its content with state surveillance partners and subject matter experts, 2) additional development of a queriable web interface to provide broad access to the knowledgebase content and query functions, 3) testing the inference capabilities of the knowledgebase when interacting with clinical and laboratory data streams, and 4) development of an organizational infrastructure and protocols for ongoing maintenance, versioning, and distribution of the knowledgebase. Revisions to the content and structure of the PHSkb should be guided by user feedback and the results of field testing.
The Public Health Surveillance knowledgebase (PHSkb) provides integrated, extensible domain knowledge regarding notifiable conditions in the United States. It can be used by public health professionals and information system developers to improve the quality of disease surveillance data.
Availability and requirements
Additional work is needed to validate the PHSkb contents with surveillance partners and subject matter experts. Therefore, the original source documents used to populate the knowledgebase should be regarded as the most definitive source of information regarding the notifiable disease domain. However, the PHSkb is provisionally available for access to demonstrate the methods used and to generate discussion among public health surveillance partners and system developers. The knowledgebase is available for download from the CDC ftp server http://ftp.cdc.gov/pub/epodphsi/PHSkb webcite. The database can be downloaded as three java files suitable for use with the Protégé software (version 1.9 or higher). The total file size is approximately 3 megabytes.
CDC Centers for Disease Control and Prevention
CSTE Council of State and Territorial Epidemiologists
CUI concept unique identifier
Dxplain clinical decision support software product
EMR electronic medical record
FIPS Federal Information Processing Standards
FTP File transfer protocol
ICD International Classification of Diseases
JESS Java Expert System Shell
LOINC Logical Observation Identifier Names and Codes
NNDSS National Notifiable Diseases Surveillance System
PHSkb™ Public Health Surveillance Knowledgebase
SNOMED-CT Systematized Nomenclature of Medicine-Clinical Terms
UMLS unified medical language system
URL uniform resource locator
The author(s) declare that they have no competing interests.
TD conceived of project idea, built knowledgebase, and drafted manuscript text and tables. HM assisted in knowledgebase development, imported data tables, developed custom data queries, contributed to manuscript text, and produced manuscript tables and figures. SG assisted with conceptualization of project, provided initial leadership to obtain project funding, and provided critical review of manuscript text. RH provided broad project management oversight and critical review of manuscript text. All authors read and approved the final manuscript. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the funding agency.
The authors wish to thank the following persons for their contributions to the development of the PHSkb: Sigrid Economou and Bill Parks, CDC; Cecil Lynch, University of California-Davis; Russ Cucina, Natasha Noy, David Buckeridge, Samson Tu, Larry Fagan, Mark Musen, and the Protégé Development team, Stanford Medical Informatics.
Hopkins RS, Jajosky RA, Hall PA, Adams DA, Connor FJ, Sharp P, Anderson WJ, Fagan RF, Aponte JJ, Nitsche DA, Worsham CA, Adekoya N, Chang MH, Centers for Disease Control and Prevention (CDC): Summary of notifiable diseases – United States, 2003.
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Yokoe D, Coon S, Dokholyan R, Iannuzzi M, Jones T, Meredith S, Moore M, Phillips L, Ray W, Schech S, Shatin D, Platt R: Pharmacy data for tuberculosis surveillance and assessment of patient management.
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Nationally Notifiable Infectious Diseases – Event Code List [http://www.cdc.gov/epo/dphsi/phs/files/NNDSS_event_code_list_January_2005.pdf] webcite
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The pre-publication history for this paper can be accessed here: |
<urn:uuid:756ddccb-1309-4240-a454-42a33832288b> | seed | Second Trimester: Blood Glucose
During pregnancy, up to 3% of women develop gestational diabetes (increased glucose levels). Although it can occur at any time, most cases will develop during the later part of the pregnancy. If increased blood sugar levels in the pregnant woman are uncontrolled, they can cause the fetus to increase in size and weight. They can also cause the baby to be born with very low glucose levels and to have breathing difficulties.
Most women are checked for gestational diabetes between 24 and 28 weeks of pregnancy. Sometimes a test for diabetes is done earlier in the pregnancy if a woman is suspected of having pre-existing diabetes or is considered to be at higher than average risk.
Risk factors for diabetes include:
- Older age
- Ethnicity with higher rate of diabetes such as Hispanic, Native American, South or East Asian, African American, or Pacific Islands descent
- Family history of diabetes
- Personal history of gestational diabetes with a previous pregnancy
The U.S. Preventive Services Task Force, the American Academy of Family Physicians, the American College of Obstetricians and Gynecologists (ACOG), and the American Diabetes Association (ADA) recommend that all pregnant women be screened for gestational diabetes after 24 weeks of pregnancy.
ACOG recommends screening using patient history, risk factors, or laboratory testing.
In the U.S., laboratory testing may involve either a one-step or two-step approach:
- One-step 2-hour oral glucose tolerance test (OGTT): After a fasting glucose level is measured, a woman is given a 75-gram dose of glucose to drink and her glucose levels are measured at 1 hour and 2 hours after the dose. Only one of the values needs to be above a cutoff value for diagnosis.
- Perform a glucose challenge test as a screen: a woman is given a 50-gram glucose dose to drink and her blood glucose level is measured after 1 hour.
- If the challenge test is abnormal, perform a 3-hour oral glucose tolerance test. After a woman's fasting glucose level is measured, she is given a 100-gram glucose dose and her glucose is measured at timed intervals. If at least two of the glucose levels at fasting, 1 hour, 2 hour, or 3 hour are above a certain level, then a diagnosis of gestational diabetes is made.
ACOG currently recommends the two-step approach while the ADA says either the one-step or two-step approach is appropriate.
For women with gestational diabetes, diet control and/or insulin injections throughout the rest of the pregnancy may be required to bring glucose levels down to normal levels. In most cases, gestational diabetes will go away after delivery, but women who have gestational diabetes will be at an increased risk of having it again with subsequent pregnancies and of developing diabetes in the future. Some organizations, including ACOG and the ADA, recommend that women diagnosed with gestational diabetes be screened 6-12 weeks after delivery for diabetes that persists.
National Diabetes Information Clearinghouse: What I Need to Know about Gestational Diabetes
American College of Obstetricians and Gynecologists: Gestational Diabetes
Centers for Disease Control and Prevention: Type 1 or Type 2 Diabetes and Pregnancy |
<urn:uuid:faed0b02-ce1f-47a0-93ba-82816f569819> | seed | | Discussion: |
Phyllodes tumor is a rare breast tumor that forms from the stroma (connective tissue) of the breast. It is characterized as a rapidly growing mass that is sharply defined with lobulated contours. Its ultrasound appearance is similar to that of a fibroadenoma. On ultrasound the phyllodes tumor appears hypoechoic, with fine or coarse internal echoes, and it has a variable effect on posterior echoes. The phyllodes tumor appears to arise from the connective tissue of the lobule, as does a fibroadenoma. The convoluted hypercellular overgrowth found in this tumor causes elongation and distortion of the ducts that produce slit-like, epithelium lined clefts and cystic spaces. Usually the tumor is more cellular than a fibroadenoma which is evident in the stroma closest to the stretched ducts that are found within the tumor.
Phyllodes tumors may be classified as benign, malignant, or borderline by histologic analysis of mitotic activity, cytologic atypia, and infiltrative versus pushing margins. Increased mitoses characterize the malignant forms. Phyllodes tumors are usually benign but approximately 15% are malignant and are locally invasive, recurrent, or metastatic beyond the breast. Approximately 25% recur locally if not completely removed, and as many as 10% may metastasize (usually to the lung and not to the axillary lymph nodes).
Phyllodes tumors do not respond to hormonal therapy and are less likely to respond to other breast cancer treatments such as chemotherapy or radiation therapy. So the treatment of these tumors is surgical removal. Benign phyllodes tumors are treated by removing the mass and a 2 cm area of normal breast tissue from around the tumor. Malignant phyllodes tumors are removed in the same manner with a wider margin of breast tissue or by total mastectomy if needed. |
<urn:uuid:c4503637-5e82-465f-b9ef-ba5376aefb46> | seed | New research from the Netherlands shows that the switch from screen film mammography (SFM) to digital mammography (DM) in large, population-based breast cancer screening programs improves the detection of life-threatening cancer without significantly increasing detection of clinically insignificant disease. Results of the study are published online in the journal Radiology.
DM's higher sensitivity at detecting breast cancer raised concerns that its introduction into screening programs would increase the diagnosis of clinically unimportant cancers-cancers that, if left undetected and therefore untreated, would never have surfaced clinically in the person's lifetime. Data analysis showed an increased incidence of ductal carcinoma in situ (DCIS), a precursor for invasive breast cancer, in the years after the introduction of population-based screening with DM. The development of low-grade DCIS can extend over more than three decades; however, high-grade DCIS is associated with far more rapid cancer invasion.
"More DCIS and invasive cancers are detected with the use of DM in breast cancer screening compared to SFM," said Adriana M.J. Bluekens, M.D., from the National Expert and Training Centre for Breast Cancer Screening in Nijmegen and St. Elisabeth Hospital in Tilburg, both in the Netherlands. "In the mix of low- to high-grade DCIS lesions, there is no shift to the detection of low-grade lesions in digital screening. Instead of this, we noticed a larger amount of high-grade lesions, which are regarded as precursors of high-grade invasive tumors."
To learn more about the impact of DM on screening programs, Dutch researchers compared it with SFM in screening mammograms performed between 2003 and 2007. Recall was indicated in 18,896 cases out of almost two million mammograms studied, and 6,410 women were diagnosed with breast cancer. As expected, DM had a higher initial sensitivity for detecting cancer, with a detection rate per thousand of 6.8, compared with 5.6 for SFM.
Detection of high-grade DCIS with DM was 58.5 percent, compared with 50.5 percent for SFM.
"This gain is largely due to enhanced depiction of microcalcifications with DM resulting in improved detection of DCIS and invasive carcinoma with an intraductal component," Dr. Bluekens said. |
<urn:uuid:f8e3be5f-f698-47c8-8b3a-7a3d12abcf39> | seed | Fluorescence Microscopy Image Gallery
Specimens featured in the fluorescence digital image gallery are derived from a combination of stained thin sections, whole mounts, suspensions, smears, and several additional mounting techniques. Stained tissue culture cells and thin sections were labeled with either fluorescent dyes or common histology stains such as eosin, fast green, and safranin. Fluorescence microscopy and photomicrography was conducted by Charles D. Howard. Background research for the figure captions was provided by Elise Sessions. Kathleen Carr supervised the authoring and assembly of text for each of the gallery entries.
Fluorescence Microscopy of Cells in Culture - Serious attempts at the culture of whole tissues and isolated cells were first undertaken in the early 1900s as a technique for investigating the behavior of animal cells in an isolated and highly controlled environment. The term tissue culture arose because most of the early cells were derived from primary tissue explants, a technique that dominated the field for over 50 years. As established cell lines emerged, the application of well-defined normal and transformed cells in biomedical investigations has become an important staple in the development of cellular and molecular biology. This fluorescence image gallery explores over 30 of the most common cell lines, labeled with a variety of fluorophores using both traditional staining methods as well as immunofluorescence techniques.
Alfalfa Root - Alfalfa, or Medicago sativa, is a deep-rooted perennial native to the Mediterranean region near Iran but which also grows well in North America and Western Asia. Also called Lucerne, or Purple Medic, it looks very much like clover with a smooth, erect stem growing 2 to 3 feet tall, grayish-green feathery trifoliate leaves, and egg-shaped leaflets. It is tolerant of a wide range of climatic conditions and can be grown in cool, humid environments as well as irrigated arid regions.
American Dog Tick - The American dog tick is one of the ticks that harbor the organism that causes Rocky Mountain spotted fever, the most common tick-borne disease in the United States. The illness was first spotted in Montana and Idaho, although it is now prevalent in the southeast. Symptoms include sudden high fevers, severe headaches, fatigue, muscle aches, nausea, and sometimes rashes. Usually symptoms become apparent 3 to 12 days after the victim has been bitten.
Ant (Formicidae) - Ants are one of the most successful groups of insects to inhabit the Earth during the past 100 million years. All ants belong to the insect family Formicidae in the order Hymenoptera, the same order comprising bees and wasps, and are believed to have descended from a wasp-like ancestor. The social behavior of ants, which exhibit a predominately female society made up of three castes, is one of the most complex of the insects.
Antelope Hair - Antelopes are even-toed ruminants belonging to the family Bovidae, order Artiodactyla. This family includes bison, buffalo, cattle, sheep and goats. Antelopes are herbivores, native to Africa and parts of Asia. Pronghorn antelopes, which belong to the family Antilocapridae, are native to North America, but are not true antelopes because they annually shed the outer sheath of their branched horns unlike other antelope species.
Basswood (Tilia) Root - Basswood trees are characterized by tall, straight trunks and a deep wide-spreading root system that makes them less vulnerable to wind than many other species. The American basswood, scientifically described as Tilia Americana, is also renowned for its heavy foliaged crown that features dark green heart-shaped leaves that reveal more lightly colored glistening undersides when rustled by a breeze. The hardwood tree is well suited for growth in the fertile soils of the northeast United States, where it proliferates in great numbers as a favorite ornamental shade tree.
Basswood (Tilia) Stem - Basswood seeds and twigs are a popular food for wildlife and the flowers smell and taste like honey, attracting over 60 insect pollinators, especially honeybees. The soft, light-colored wood has an even grain, long favored by wood carvers. Native Americans used the fibrous inner bark to make rope, which was used to bind wounds and stitch mats made from cattail leaves.
Bed Bugs (Cimex lectularius) - Bed bugs feed primarily on human blood, but can be found on bats, rabbits, domestic animals, and other warm-blooded mammals. They also have the ability to survive long periods of starvation and adverse temperatures. Bed bugs are mentioned in early European history and literature and are believed to have been transported around the world by clothing and bedding. Today, they are found in both temperate and tropical regions.
Bird Lungs - At rest, a bird's oxygen consumption rate is higher than all other vertebrates. That rate is even higher when engaging in activities such as flying. Birds are capable of high rates of gas exchange because of the special construction of their lungs, and additional breathing organs, a complex series of air sacs. Connecting tubes join the lungs to these air sacs, increasing a bird's respiratory capacity to about twice that of any mammal of comparable size.
Bird Skin - Birds have a thin and delicate epidermis, or skin, compared to other vertebrates. Their skin produces specialized structures called feathers, which is one of the unique characteristics of birds. Feathers are made up of keratin, a flexible protein that also forms the hair and fingernails of mammals. Over the past 100 million years, feathers have evolved a variety of forms. Thick epidermal scales, like those found in reptiles, usually cover exposed areas of skin, such as the legs and feet.
Black Grape Rot - Black rot, caused by the fungus Guignardia bidwellii is one of the most serious diseases of cultivated grapes in the eastern United States, especially in warm, humid areas. Crop losses due to black rot can be devastating, ranging from 5 to 80 percent depending on the weather, the variety of grape being grown, and the amount of disease in the vineyard. The fungus can infect all green parts of the vine but the most damaging effect is on the fruit, which shrivel up into dark-colored mummies.
Cactus - Cactus plants are perennial succulents native to the Americas and easily grown in almost all warm and arid climates around the world. The ability to sustain extreme temperatures makes them one of the heartiest plants on earth. Thorns, hairs, and layers of wax are some of the characteristics of cactuses that help to maintain their core temperature. Large systems of roots and fleshy stems help the cactus plants to absorb large quantities of water when available and store it through long periods of drought.
Clubmoss (Lycopodium) - Historically, clubmosses have endured many climatic and environmental changes. The plants were particularly abundant hundreds of millions of years ago during the Paleozoic era, when they grew to massive proportions and dominated the Earth. Today, clubmosses are much smaller and are primarily native to mountains in the tropics, though they may also be found in northern forests. The exact dimensions of the plants are dictated by species, but a typical example is stag's horn moss (L. clavatum), which features creeping stems about 10 feet long and has approximately 4-inch-high ascending branches.
Corn Grain - Corn is the common name for the cereal grass widely grown as food for humans and animals. Along with wheat and rice, it is one of the world's chief grain crops and the largest crop grown in the United States. Native to the Americas, corn (Zea mays) is the domesticated variety of the Zea grass family, originally cultivated by Native Americans 8,000 to 10,000 years ago. There are many varieties of domestic corn, most of which were developed through the aggressive breeding programs of the twentieth century.
Corn Smut - Smut is a disease of cereals, corn, grasses, onions, and sorghum that can be caused by any of more than 700 species of parasitic fungi. Smuts generally have a negative economic impact on agriculture, because they affect so many food crops. An exception to this is corn smut, which is considered a delicacy in Mexico. In the United States, after decades of trying to eradicate corn smut, some farmers are attempting to grow corn with large corn smut infestations because the fungus is becoming a prized gourmet food item, garnering much higher prices than healthy corn.
Dogfish Shark Placoid Scales - The bodies of dogfishes, like all sharks, are externally lined with placoid scales, also known as dermal denticles. The scales, which unlike other types of fish scales do not get larger as the shark grows, are similar in structure to teeth, consisting of three layers: a hard outer enamel-like layer, a middle stratum of dentine, and a central vascular pulp cavity. The scales are arranged in a slanting pattern pointed towards the tail of the shark that helps decrease the amount of friction the animal incurs while swimming. If the surface of a shark is rubbed from head to tail, it feels smooth, but stroking the animal in the opposite direction causes it to feel very rough.
Down Feathers - Down feathers are the soft, fluffy feathers that first appear on young birds and that also form the protective undercoat of many avian adults. Slightly different in structure, down feathers do not feature the interlocking barbs that help give other types of feathers their strength. However, since their primary function is to provide warmth and insulation, their relative weakness is inconsequential. In fact, down feathers are so well-suited to their role as insulators, humans often utilize them to stuff winter coats and bedding, such as comforters and sleeping bags.
Dutchman's Pipe - A native of central and eastern North America, Dutchman's pipe, Aristolochia durior, is a climbing vine and part of the birthwort family. The vine is planted often as a screen or cultivated as a porch vine because it is easy and quick to grow. It is distinguished by its large heart-shaped leaves and yellowish or purplish tubular flowers that resemble traditional Meerschaum smoking pipes. One curious attribute of the flowers is that they give off an aroma reminiscent of rotting meat.
Elderberry (Sambucus canadensis) - About 30 species of Elderberry make up the genus Sambucus of the family Caprifoliaceae. Elderberry bushes can be found in most forested temperate or subtropical areas around the world. In horticulture, the bushes are often used as garden shrubs and are well known for their fruit, which is used to make wines, syrups, cordial, jellies, pies and also serves as a source of food for wildlife.
Fava Bean Root Tip Mitosis - The fava bean plant (Vicia faba) also known as broad bean or horse bean, is a legume belonging to the pea family, Fabaceae. It is cultivated for its seeds, six to eight beans resembling large round limas, packed inside a large, pale-green, velvety pod. Fava beans have been an important crop in the Mediterranean area and Asia since the late Neolithic period, about 3,000 BC. Today, it has achieved a wide distribution throughout the temperate regions of the world and is one of the most important winter crops for human consumption in the Middle East.
Female Pine Cones - Pine trees are gymnosperms, non-flowering plants that produce exposed seeds not enclosed in an ovary. They are also monoecious, bearing gametes of both sexes on the same tree. These gametes are housed in a structure called a strobilus, or cone. Female pine cones are generally found in the upper branches of the tree crown, above the male cone. This reduces the possibility of self-fertilization by the wind-borne male gametes.
Fern Spores - Fern is a common name for the cryptogamous (spore-producing) plants belonging to the division Filicophyta, also called Filicinophyta. They are primitive vascular plants with true roots, stems, and complex leaves. Most ferns reproduce through the alternation of generations, alternating successive generations of sexual and asexual forms. The sexual form, called the gametophyte or prothallia, is a tiny kidney-shaped plant and difficult to find in the wild. The asexual form, known as a sporophyte, is represented by the fern plant as it is commonly known.
Fish Gill Filaments -Unlike land vertebrates or marine mammals, fish don't have lungs, but they do have paired respiratory structures called gills, or branchia. Outgrowths of the body wall, gills remove dissolved oxygen from water and expel carbon dioxide waste from the bloodstream. This is how fish can breathe underwater without ever having to come to the surface for air. When there are insufficient quantities of dissolved oxygen in the water, they will suffocate.
Fleas - Ctenocephalides felis is commonly known as the cat flea and Ctenocephalides canis is known as the dog flea. Both are members of the 1,600 species referred to as fleas, order Siphonaptera ("wingless siphon"). Adult fleas vary in length from 0.04 to 0.4 inches and are able to jump over eight inches high, which is roughly the equivalent of a human jumping over the Statue of Liberty. These blood-sucking insects can be found worldwide, from the Arctic to the tropics.
Frog Stomach Thin Section - In amphibians known as gastric brooding frogs the stomach is more than just a place for digestion to take place. The females of these species swallow their clutch of eggs and allow the tadpoles to hatch in their stomachs. It is believed that the tadpoles secrete chemicals that inhibit the production of hydrochloric acid in the stomach wall and cause the mother to desist from feeding. Once the tadpoles become fully developed froglets, they are birthed through the mouth of the mother. Scientists have been extremely interested in studying these animals in order to find information about hydrochloric acid determent that could benefit humans suffering from gastric ulcers.
Guinea Pig Hair - The guinea pig (Cavia porcellus) is a domesticated form of the cavy and is native to in South America. It is believed to have been domesticated during pre-Incan times from a wild species that lived in Peru. The animal is not, in fact, a pig but is a rodent, a relative of mice, rats and hamsters. Like other rodents, guinea pigs' teeth do not have nerves and grow continuously, like fingernails.
Head Louse - There are three species of louse that parasitize humans: the head louse (Pediculus humanus capitis); the body louse, better known as the cootie (P. humanus humanus); and the crab, or pubic, louse (Phthirus pubis). These species belong to the insect order Anoplura and have long been associated with people. Archaeologists have even found louse combs buried with Egyptian mummies, who were apparently anticipating head lice in the afterlife.
Herbaceous Stems - The stems of herbaceous plants tend to be somewhat soft and flexible because they contain very little of the woody material characteristic of bushes and trees. Instead, they are primarily composed of vascular bundles (xylem and phloem) arranged in a circle around a central core of spongy tissue made up of parenchyma cells, or pith. A layer of tissue known as the cortex surrounds the vascular bundles and may vary in thickness depending upon species. Another layer of cells called the epidermis encircles the cortex. In conjunction, the various materials of the stem carry out the structure's primary functions, which include providing support to leaves and flowers, as well as transporting water, minerals, and the products of photosynthesis throughout the plant.
Honeybee Leg - Honeybees are classified in any of the four species that belong to the genus Apis. They are classified, along with 20,000 other insect species, as members of the Apoidea superfamily (order Hymenoptera), which includes ants, wasps, hornets, and many other species of bees. A honeybee's body is divided into three segments, each one equipped with a pair of legs. Each pair of legs is highly specialized and, in combination, they make the perfect tools for collecting pollen, which provides essential proteins for honeybee larvae.
Honeybee Stinger - The stinger is located on female honeybees at the end of the abdomen and is part of the ovipositor, which is an egg-laying device. Even though most bees can sting repeatedly, a honeybee only has one chance. The honeybee stinger has a hook-shaped barb and when it catches in a victim the bee can't fly away without inflicting the fatal wound of tearing out its ovipositor along with some internal organs. Even after the bee detaches itself, the venom sac and its attached muscles continue to pump venom into the victim.
Horsetail (Equisetum) Plants - Although many horsetails have little commercial value, some have been utilized by humans for thousands of years. The horsetail scientifically described as E. arvense has been used as an herbal remedy since the early days of ancient Greece and Rome. Traditionally the plants were employed to promote blood clotting and to treat kidney infections and tuberculosis. Another useful type of horsetail is commonly known as the scouring rush. The coarse, textured plant contains a significant amount of silica granules in its cells that make it a valuable for scouring or as an ingredient in abrasive powders.
House Fly Face - The often maligned common house fly is generally thought to be a nuisance and vector for many diseases that affect both humans and animals. Flies lay up to 1000 eggs in some of the most undesirable settings such as garbage, decomposing plant and animal matter, feces, spoiled food, and manure. Although more abundant in the warm spring and hot summer weather, house flies may exist year-round in temperate climates, where their life cycles occur every eight days.
House Fly Mouth - A closer view of the house fly face, this time peering deep into the insect's mouth. Although some flies can bite, the house fly cannot. Its mouthparts consist of soft, spongy structures called the labella and proboscis. The labella gently dab liquids into its proboscis, which then sucks up the liquid. If the fly encounters solid food it wants to eat, it drops saliva onto it, turning the food into a liquid.
Human Flea - Fleas belong to the insect order Siphonaptera and parasitize mammals and birds for their blood, using specialized anatomical structures to attach to the hosts' skin. Pulex irritans, the human flea, is one of more than 1,600 species and subspecies of fleas that populate the Earth from the Arctic Circle to the deserts of Africa. As its common name suggests, the preferred food for Pulex is human blood, but it will feed on other mammals as well.
Human Hyaline Cartilage - Cartilage is a dense network of collagen fibers, embedded in a firm but plastic-like gelatinous substance, covered by a membrane called the perichondrium. Mammals have three types of cartilage: hyaline, elastic, and fibrocartilage. Hyaline cartilage is the most widely distributed form and is also the type that makes up the embryonic skeleton. In adults, it's found at the ends of bones in free-moving joints and at the ends of the ribs, and also in the nose, larynx, trachea and bronchi.
Human Roundworm - Ascaris lumbricoides, the large human roundworm, is the most massive nematode to parasitize humans, growing up to 16 inches long and often as thick as a pencil. Infections of this intestinal roundworm, called ascariasis, are extremely common in rural communities around the world and affect as many as 1.5 billion people, almost one-quarter of the world's population. Infections occur after people ingest food or soil contaminated with Ascaris eggs.
Human Scalp - In humans, the scalp is a specialized area of skin on top of the head, usually covered with hair in both sexes. It consists of three layers: a layer of skin, an underlying layer of tissue and blood vessels, and the occipitofrontalis muscle, which raises the eyebrows, stretching from the top of the eyebrows to the back of the head. The scalp covers most of the head, starting at the top of the forehead, and contains as many as 150,000 hair follicles.
Human Spinal Cord - The human nervous system carries stimuli from sensory receptors to the brain by two main parts: the central nervous system and the peripheral nervous system. The brain and spinal cord make up the central nervous system. The spinal cord represents the major nerve track in all vertebrates. In humans, the spinal cord extends from the base of the brain to the middle of the back and is about 18 inches long.
Japanese Pony Belly Hair - Hair is a unique attribute of mammals and serves a variety of functions, although the primary function of hair is to preserve body heat. Japanese ponies are particularly famous for their hair. Its soft and luxurious feel to the skin has made Japanese pony hair a favorite in the world of cosmetics, used for powder brushes and other face brushes. Recently the pony hair market has expanded to include clothing, shoes and even toys.
Kapok Fiber - Kapok fiber is a silky cotton-like substance that surrounds the seeds in the pods of the ceiba tree. The ceiba tree belongs to the Bombacacae family and is primarily found in Asia in tropical and semi-tropical climates, at an altitude less than 1000 feet, in porous volcanic soil. The fiber is removed by hand, dried, separated from the seeds and prepared for export. It is too brittle and inelastic to be spun, but it is ideal for stuffing life preservers and other water-safety equipment because of its excellent buoyancy.
Leech - Leech is a common name for over 650 species of carnivorous, bloodsucking annelid worms that make up the class Hirudinea of the phylum Annelida. They are equipped with a large and a small sucker. The mouth is located on the small sucker and has three jaws with sharp teeth that make a y-shaped incision in the flesh. When a leech punctures the skin it anesthetizes the wound with its saliva, so that often the victim does not feel a thing.
Lily Flower Bud - Richly symbolic, lilies have a long history of special significance to humans. Minoans believed the plants were sacred and associated them with their goddess Britomartis. In fact, Minoan artifacts exhibiting representations of lilies have been discovered that date back to around 1580 BC. Ancient vases and relics etched with lilies have also been found in Egypt, where the plants were often revered as symbols of light. In ancient Greece and Rome, however, lilies were emblematic of innocence and were woven into crowns worn by brides during their weddings, a tradition carried over into modern times by brides carrying lily-filled bouquets.
Lily Seeds - Lilies are herbaceous flowering plants that thrive in warm temperate and tropical climates. As monocots, the bisexual lily buds typically exhibit three sepals, three petals, and six stamens, each bearing a bilobed anther containing four pollen sacs. Additionally, the buds feature a single central pistil leading to an ovary, usually with six ovules, which is enclosed by three fused carpals. Although sexual reproduction by seed is possible, lilies are usually commercially grown via asexual bulbs to ensure that the plants maintain enough energy for flowering.
Lone Star Tick - Amblyomma americanum is commonly known as the Lone Star tick. It's named for the dramatic iridescent spot that can be found on the female. Lone star ticks are found primarily in northern and central Florida, but can also be found in the mid-Atlantic and south-central parts of the United States, as well as Mexico. The ticks are reported to transmit Rocky Mountain spotted fever, Q fever, tularemia, and Lyme disease.
Mammalian Compact Bones - There are two basic structural types of bone in mammals, compact and spongy. Compact bone is very dense and hard on the outside, and makes up most of the bones in the arms and legs. The structural units are osteons, which are elongated cylinders acting as weight-bearing pillars that can withstand high levels of mechanical stress.
Mammalian Spongy Bone - Spongy bone, also known as cancellous bone, is less dense than compact bone and is composed of a honeycomb-like network of bones called trabeculae. Spongy bone actually looks like a sponge. It is found at the expanded heads of long bones, such as bones of the arms, legs, fingers and toes. The material also fills most irregular bones, such as bones of the skull, vertebrae and hips.
Milkweed Fibers - Milkweed is a perennial plant whose species are native primarily to North America. It can be found growing in prairies, pastures, along roadsides and on the banks or edges of ponds and lakes. As suggested by its name, milkweed contains an abundance of milky sap in its leaves, stems and pods. A healthy plant can reach nearly 5 feet, thriving in full to partial sun in all types of soil.
Mite - There are over 20,000 species of mites, tiny anthropod invertebrates belonging to the class Arachnida. Along with the tick, they make up the order Acarina. Mites can be found worldwide in diverse habitats, including brackish water, fresh water, hot springs, soil, plants, and mosses as well as upon and inside animals. Parasitic forms may live in the nasal passages, lungs, stomach, or even deeper body tissues.
Mosquitoes - Despite the bad reputation of mosquitoes, male mosquitoes do not bite, but harmlessly feed upon plant and fruit juices. It is only the females who require blood meals, due to a need for extra protein to produce eggs. In order to locate their victims, the females utilize a variety of cues, including sight, scent, and heat. From as many as 100 feet away, the insects are capable of detecting the scent of potential hosts, especially the carbon dioxide they exhale.
Moss Reproductive Tissue - Mosses are the most common, diverse, and advanced group of bryophytes, a division of green, seedless plants that dates back to the Permian period (286 to 245 million years ago). In Bryophytes, the antheridium is the male sex organ, which produces sperm. The archegonium is the female reproductive organ, which produces eggs. Both types of reproductive tissue are generally found at the tips of the main plant shoots.
Mouse Intestines - Laboratory mice are special breeds of house mice and are used in many scientific experiments because of their close mammalian relationship to humans. Mouse intestines, for instance, are very much like those of other vertebrate animals. The large intestine is wider and shorter than the small intestine and its primary function is to absorb water and electrolytes from digestive residues and store fecal matter.
Mouse Kidney - The kidney is an organ that maintains water balance and expels metabolic wastes in vertebrates and some invertebrates. Primitive and embryonic kidneys have sets of specialized tubules that empty into two collecting ducts that pass urine into a primitive bladder. The more advanced mammalian kidney is a paired compact organ with functional units, called nephrons, that filter the blood, reabsorbing water and nutrients and secreting wastes, producing the final urine.
Mycorrhizal Fungi - Most plant species are better able to utilize the soil in which they're growing with the help of beneficial microorganisms called mycorrhizal fungi. These fungi live in symbiosis with plants, growing on the surface of their roots (ectotrophic) or actually invading the hosts' roots (endotrophic). The fine threads that make up the mycorrhizal fungus permeate soil particles, grow into decomposing organic matter, and even explore the shells of dead insects where they find phosphorus and other vital nutrients. The nutrients absorbed by the fungi are then passed back into the roots of the plants providing a major benefit to the plant--improved uptake of soil phosphorus.
Obelia Hydroid: First Generation - Obelia belongs to the phylum Cnidaria, which includes corals, sea anemones, jellyfish, and the freshwater hydra. The many species of this genus are widely distributed throughout all the oceans and are typical of cnidarians, both in their morphology and their life cycle. These animals take two generations to complete one life cycle, one of which consists of polyps living in hydroid colonies.
Oleander Leaf - Oleander, Nerium oleander, is an ornamental evergreen that belongs to the dogbane family, Apocynaceae. The plant is beautiful, but extremely deadly. A single leaf can kill an average size adult. In fact, all parts of the plant are highly toxic if ingested. Oleander contains a poisonous glycoside, a milky substance that is rich in salicine and other alkaloids. This poisonous sap can paralyze the hearts of humans and animals.
Peach Brown Rot Fungus - Peach brown rot is a serious disease of fruit trees caused by the fungus Monilinia fructicola. Also affected by this devastating fungus are other stone fruits such as cherries, plums, prunes, nectarines, and apricots. The fungus forms cankers on the twigs of the fruit trees, but it does the most damage when it rots blossoms and fruit. At harvest, apparently healthy fruit may be contaminated with spores and decay during storage and marketing.
Peach Leaf Curl - Peach leaf curl is a common disease of peach and nectarine trees caused by the fungus Taphrina deformans. Spores of the fungus overwinter on the surface of peach twigs. In spring, the spores multiply during periods of moist weather until the leaf buds swell and open. Rain is necessary for infection, carrying the spores on a thin film of water into the buds, where leaves are infected. After the deformed and discolored leaves turn brown and fall, they produce powdery gray spores.
Pectinatella Bryozoans - Colonies of Pectinatella species and other bryozoans increase rapidly in size, sometimes doubling in diameter over the course of a few days if proper conditions and abundant food are present. P. magnifica prefers warm temperatures and feeds on small aquatic plants and animals such as diatoms, algae, and bacteria. To do so, the zooids utilize specialized feeding structures known as lophophores that are ciliated and can be extended or retracted as needed. If the environment becomes unfavorable, however, perhaps due to the approach of winter, the colonies produce statoblasts, which are more able to withstand extreme conditions.
Pine Needle Cross Section - Due to the efficiency of their needles, pine trees remain covered in leaves year-round and are commonly known as evergreens. Older needles drop off periodically (usually when they are two to four years old), but they are continuously replaced with new growth. The needles grow in sheathed bundles, arranged spirally along supporting shoots. The number of needles in each bundle may vary, but they generally contain two to three needles on hard pines and five on soft pines.
Pine Root - The root system is the part of a plant that normally grows underground. Its primary functions are anchorage of the plant, absorption of water and dissolved minerals, conduction of these to the stem, and storage of reserve foods. Gymnosperms, such as pine trees, have a taproot system. A primary root, or taproot, emerges from the seedling and secondary roots grow laterally from it. The taproot grows deep into the ground, enabling the tree to withstand long periods of drought.
Pine Tree Pollen - Pine trees are gymnosperms, nonflowering plants that produce exposed seeds not enclosed in an ovary. These gametes are housed in a structure called a strobilus, or cone. The male pinecone produces the pollen, or male gametes. The cones are covered with fertile scales (modified leaves), each of which bears two pollen sacs. In the spring or early summer, the pollen sacs release their pollen grains, each of which has two air bladders for wind dispersal.
Pine Wood - Pine is the common name for species belonging to the genus Pinus, a member of the family Pinaceae, resinous trees with needle-like leaves. Pine trees are evergreens found worldwide, primarily in northern temperate regions. Typically they have woody stems covered in bark, which protects tissues that conduct nutrients and water. When harvested, they provide materials like lumber, turpentine, rosin, paper, pulp, fuel and even food (pine nuts).
Privet Leaf - About 50 species of privet shrubs and small trees belong to the genus Ligustrum of the Olive family, Oleaceae. They grow quickly and are popularly used as hedges and screens. Privets are native to Europe, Asia, and the Mediterranean regions. Their flowers bloom in clusters, or panicles, of small white blossoms.
Raw Meat - For millions of years, the human diet has included the edible portion of animal tissues, or meat. Meat is an excellent source of protein, providing all nine essential amino acids in addition to vitamins and minerals. There are three types of muscle: smooth, cardiac, and skeletal, but skeletal muscles make up most meats and meat products.
Rhizopus Rot - Rhizopus rot is a soft rot of harvested or over-ripe stone fruits, such as peaches, nectarines, sweet cherries, and plums. Mold species belonging to the genus Rhizopus cause the rot, which initially appears on the fruit as a fuzzy white mass called the mycelium. The fungus produces enzymes that deteriorate the tissue holding the skin to the flesh of the fruit. Later, it turns dark gray to black as the fungus begins to develop sporangia, the fruiting structures that produce spores.
Smilax Root - Humans have utilized Smilax vines for a variety of purposes throughout history. Some types are edible, while others, such as the carrion flower (S. herbacea) and the common greenbrier (S. rotundifolia) are cultivated to create impenetrable thickets. The desirability of using carrion flowers as ornamentals, however, is questionable due to their blossoms, which are reminiscent of rotting meat and are pollinated by flies. Also, the perennials can cause problems when they invade crops of fruit, a fairly frequent occurrence in the southeastern United States.
Snail Radula - Snails have a large foot for creeping along surfaces, a single coiled shell that encloses the organs, and a head with eyes and tentacles. Like most other gastropods, snails feed by using a specialized rasping organ called a radula. It is a ribbon-like structure covered with small horny teeth called denticles that tear food into pieces that are then collected by lips or a proboscis. New denticles are constantly being produced to replace those worn away at the front.
Sweet Flag Grass - Sweet flag, taxonomically classified as Acorus calamus, is a grass-like perennial that can grow up to 2 meters or 6.6 feet high. Along with the common cattail, sweet flag thrives in wet areas like the edges of streams, ponds, and lakes. The thick, erect leaves of the plant resemble those of an iris and, though it rarely flowers, its blossoms are greenish brown cylinders covered in little, rounded spikes.
Trichina Worm - Trichina (Trichinella spiralis) is a parasitic nematode worm that causes trichinosis, a serious disease in humans and other meat-eating mammals. The most common way that humans become infected with trichinosis is by eating raw or undercooked pork. People can also become infected by eating wild game, such as bear, cougar, fox, dog, wolf, horse, seal, or walrus. As of now, there is no known specific treatment for trichinosis, but it can be prevented.
Wheat - Wheat is the common name for any of the cereal grasses belonging to the genus Triticum and is an important food source for people around the world. In fact, it is the most common grain cereal today, world wheat production totaling more than 590 million metric tons in 1990. Evidence shows that wheat grew as a wild grass in the Middle East nearly 10,000 years ago and was in cultivation by 6,000 BC.
Wheat Kernel - Wheat grains can be eaten by simply soaking and cooking the grain. The majority of food uses, however, require more processing. First, the grain is cleaned and conditioned by adding water. This causes the kernel to break up properly when it is milled. During the milling process, the grain is cracked, then flattened by rollers. This process continues and particles are sifted by size until about 70 percent of the grain has been powdered into flour.
Wheat Rust Pustule - Wheat rust is a common and serious disease, reducing crop yields both in the United States and in other wheat-growing areas of the world. It is caused by a parasitic fungus and can affect both the leaves and stems of wheat plants. In individual fields, the disease accounts for crop losses ranging from trace amounts to as much as 40 percent when weather conditions are favorable for fungus growth.
Young Starfish - Despite their name, starfish are echinoderms, not fish. They breathe through structures on their hard, spiny skin rather than gills and move through the use of the rows of tube feet that line the bottom of each of their arms instead of swimming. The tube feet are also utilized for detecting smells and tastes, as well as for sweeping food into the mouths of primitive starfish species. Most of the more advanced varieties of the creatures, however, protrude their stomachs out of their mouths to surround prey.
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<urn:uuid:1d147c5f-ac04-4f0f-9a1f-e9ea6584f466> | seed | RNA once is considered as the fundamental information medium in central dogma of molecular biology. A number of studies have indicated that RNAs play a more active role and carry diverse functionalities in nature, including mediating the synthesis of proteins, regulating cellular activities, and exhibiting enzyme-like catalysis and post-transcriptional activities. Furthermore, many recent discoveries have shown that the number and biological significance of functional RNAs has been underestimated. In living cells, RNAs do not remain in a linear form, which folds its secondary structure through base pairs including canonical bonds of A-U and G-C and wobble pair of G-U. For understanding RNA's functionality, the alignment and similarity of RNA should consider not only the primary structure (sequence) but also the secondary structure (base pairs).
Numerous approaches were proposed to measure the similarity between RNA secondary structures, which can be broadly categorized into two classes: alignment based string or tree representation of RNA secondary structure, and comparison based some numerical representation without alignment.
Most studies usually adopt dynamic programming algorithms and tree models. Some are usually based on the alignment of a string representation of the secondary structures such as the dot-bracket representation, in which a score function or a distance function to represent insertion, deletion and substitution of letters in the compared structures [1
]. Sequences considered in alignment of RNA secondary structures are not only string sequences but also secondary structure. Different weights or different score functions are designed for unpaired nucleotides and paired nucleotides.
Others are almost based on alignment of a tree representation of the RNA secondary structure elements or the base pairing probability matrices [5
]. Shapiro [5
] proposed various tree models used for representing RNA secondary structures without pseudoknots.
Each tree model offers a more or less detailed views of an RNA structure. Given the tree representations of two RNA secondary structure, one comparison way is based on the computation of the edit distance between the trees while the other focus on the alignment of the trees using the score of the alignment as a measure of the distance between the trees. Popular tools for optimal alignment of RNA secondary structures include RNAdistance [6
] and RNAforester [8
] etc. RNAdistance compares RNA secondary structures based on tree edit distance measure, while RNAforester computes the pairwise or multiple alignment of structures based on tree alignment measure. Hofacker [9
] measured RNA secondary structures in terms of the base pairing probability matrices computed by McCaskill's partition function algorithm [10
]. The popular tool based matrix of base pairing probabilities is RNApdist, which was implemented as part of the Vienna RNA package.
Because the above methods rely on dynamic programming algorithms, they are computation-intensive even if the pseudoknots are ignored. For example, the Sankoff's algorithm [11
] simultaneously allows the structure prediction and alignment problem with O
) in memory and O
) in time for two RNA sequences of lengthn. So these algorithms are still impractical for long RNA sequences. Recently some comparison algorithms without aligning them are proposed. Kin [12
] gave a kernel method based on Stochastic Context Free Grammar (SCFG).
The graphical representations of biosequences (protein, DNA and RNA) could be out of the mainstream but a new research view and tool to understand and analyze such biosequences. M.Randic [13
] reviewed the sufficient materials on related topics of graphical representations of protein, DNA and the secondary structure of RNA. Inspired by several graphical representations of DNA sequences [14
], some researchers have proposed 2D, 3D or 4D graphical approaches for the representations of RNA secondary structure and then derive some numerical invariants and different graphical measures from graphs to compare RNA secondary structures [19
], eight symbols of the unpaired bases A, C, G, U and paired bases A′, C′, G′, U′ were used to code RNA secondary structures as graphical representations. In [31
], the representations of eight letters have been demonstrated to be approximate and have some loss of information. In [32
], 12 symbols have been used to represent RNA secondary structure without loss of information, in which the key is to discriminate between the first and the second base of a hydrogen bond for the paired bases.
In this paper, motivated by DV curve representation of DNA sequences [33
], we propose a novel triple vector curve representation of RNA secondary structure. With this novel representation, a new RNA secondary structure similarity measure based on wavelet analysis is designed, which can simultaneously focus on the local structure and global structure. To evaluate our algorithms, we take the classification of non-coding RNA and RNA mutation as examples to compare to the two popular tools of RNAdistance and RNApdist. |
<urn:uuid:3e21f30c-e596-4fa3-9e92-0606514534a0> | seed | The flu season is still young in the United States and the rest of the Northern Hemisphere, but Australia wrapped up its flu season months ago, and public health officials there have some disturbing news to report: The version of so-called swine flu that is resistant to the drug Tamiflu is spreading more easily in the land Down Under.
For those in need of a refresher course, swine flu refers to the H1N1 flu virus that caused a pandemic in 2009. It emerged in April in Mexico and spread swiftly around the globe, traveling to 214 countries and territories and killing more than 18,000 people, according to the World Health Organization. Humans were unusually vulnerable to this particular strain - a combination of viruses from birds, pigs and people - because their immune systems had never encountered it before.
Tamiflu, also known by the generic name oseltamivir, was frequently prescribed to patients, and it didn't take long for a version of H1N1 to emerge that was resistant to the drug. Luckily, this strain was a minor player, infecting less than 1 percent of people who were tested. In those cases, it spread between people only when they were in closed settings or had close contact with one another.
Fast-forward to 2011. In and around the Australian city of Newcastle, the Tamiflu-resistant H1N1 virus was spreading more easily among humans, according to a report being published in Thursday's edition of the New England Journal of Medicine.
Public health officials took virus samples from 182 patients treated in doctors' offices and hospitals between May and August. They found that 29 of those samples - or 16 percent - turned out to be resistant to Tamiflu.
The 29 patients ranged in age from 4 months to 62 years, with a median age of 31; 17 of the patients were female, including three who were pregnant. Among all 29 patients, the most common flu symptoms were cough (experienced by 86 percent of patients) and fever (affecting 76 percent of patients). Seven patients required admission to the hospital, but none was treated in the ICU and none died.
Genetic analysis of the flu samples revealed that all of the 29 patients were infected with a single strain. Most of these patients lived within about 30 miles of Newcastle, the seventh largest city in Australia. (Two related strains were detected elsewhere in Australia, including 100 miles away in Sydney, the country's largest city.)
It is unclear how the Tamiflu-resistant strain spread from person to person. Eight of the patients lived with another person who was infected, and two other patients rode together in a car. The rest of the patients "had no known epidemiologic link," according to the report.
The authors of the report, including three scientists working for the World Health Organization, warned flu experts in the Northern Hemisphere to be on the lookout for this flu strain - or any other strain that is resistant to Tamiflu - this winter. |
<urn:uuid:242c5b92-6cda-4998-82b9-a5fa106674aa> | seed | The immune system is closely intertwined with both cancer pathogenesis and treatment. On the one hand, cancer is a manifestation of failures in immunity. Cancer cells that express mutant proteins manage to escape detection and elimination by the immune system. Chronic infections that persist due to incompletely effective immune responses also contribute to cancer. Some, such as human papillomavirus (HPV) and Epstein-Barr virus (EBV) are directly oncogenic, while others such as H. pylori, hepatitis C virus, hepatitis B virus and Chlamydia psittaci promote cancers by inducing chronic but ineffective immune stimulation. Similarly, chronic autoimmunity is linked to lymphoid malignancies or, in the case of inflammatory bowel disease, to colon carcinoma. Machinery that evolved for the generation of antigen receptor diversity on immune cells is co-opted in oncogenesis. On the other hand, the potency and specificity of the immune system can be a powerful tool that eliminates neoplastic cells. The success of the antibody Rituxan in treating CD20+ lymphomas and allogeneic stem cell transplantation (alloSCT) in treating hematopoietic malignancies highlights the potential of both antibody and T cell-based therapies. Nevertheless, immunotherapy of cancer is clearly in its infancy and recent and ongoing advances in basic immunology only now make it possible to more rationally explore the potential of the adaptive immune system to treat cancer.
With this background in mind, the goals of the Cancer Immunology Program are to:
- Elucidate the fundamental nature of molecular and cellular mechanisms of immunity. Basic research in immunology is conducted in four thematic areas: a) antigen presentation, b) T cell responses and their regulation, c) innate immunity and the links between the innate and adaptive immune system, and d) B cell function and cell biology. Seminal discoveries made at Yale in the fields of antigen processing, antigen cross-presentation, Toll-like receptor (TLR) function and mechanisms of T cell regulation and polarization have already begun to influence studies in the clinic.
- Encourage research in human cancer immunology. The Cancer Immunology Program has a core group of investigators that use mice to investigate cancer immunity in models of allogeneic stem cell transplantation, melanoma, breast cancer, HPV infection and cutaneous malignancy. This work is strongly supported by the outstanding immunology research in non-cancer specific models. Since communication between these two groups is essential to achieve this end, a major goal is to ensure that such interactions remain effective and robust.
- Develop and implement novel investigator-initiated trials in cancer immunotherapy. The Cancer Immunology Program has ongoing programs and therapeutic trials in allogeneic stem cell transplantation, extracorporeal photopheresis, melanoma immunotherapy, and vaccine development. |
<urn:uuid:cd935014-dc29-4271-bbb1-0be3162008b8> | seed | A new antibiotic called Fidaxomicin is now being marketed in the UK for treating Clostridium difficileinfectionInvasion by organisms that may be harmful, for example bacteria or parasites. (CDI), which is one of the most dangerous forms of hospital acquired infections (HAIs). Under the NHS, the new drug is accepted for restricted use within NHS Wales for the treatment of CDI in adults with severe cases of CDI and or CDI recurrence. From April 2011 to March 2012 CDI affected over 2,100 people in Wales.
So, how efficacious is the new drug? In clinical trials, fidaxomicin demonstrated a similar efficacy and safety profile to the current “gold standard” antibiotic, which is vancomycin (primary endpoint). However, perhaps of greater interest, more than halved the rate of recurrence in patients with CDI compared to vancomycin, (12.7% versus 26.9%). Recurrence of CDI occurs in up to 25% of patients within 30 days of initial treatment with current therapies.
Treatment withFidaxomicincosts £135 per day and so the cost of a ten day treatment course is £1,350.00.
The National Institute for Health and Clinical Excellence (NICE) has reviewed fidaxomicin under its new ‘Medicines and Prescribing Evidence summaries’. This is a summary of the best available evidence for fidaxomicin. The topics selected for these summaries are medicines that have recently gone into the UK market, or medicines that may be marketed in the UK in the next 6-12 months. It is not formal guidance.
The overall incidenceThe number of new episodes of a condition arising in a certain group of people over a specified period of time. and type of adverse events reported in clinical trials were similar between patients receiving fidaxomicin or oral vancomycin. Fidaxomicin was generally well tolerated and few patients discontinued therapy. However, the safety profile of fidaxomicin is based on only data from 564 patients in phase 3 studies. The most common treatment related adverse reactions were vomitingExpusion of the contents of the stomach through the mouth. (1.2%), nausea (2.7%) and constipationa common condition where stools are not passed as frequently as normal (1.2%). |
<urn:uuid:127b72fd-b21a-4775-88f0-d16e07fc8986> | seed | Submitted to: Current Opinions in Orthopedics
Publication Type: Review Article
Publication Acceptance Date: September 1, 1998
Publication Date: N/A
Interpretive Summary: Boron and copper are examples of elements that are present in man in small or "trace", but important amounts. When there is not enough copper in the diet, the long bones, like the femur, develop abnormally and they become thin and fracture easily. In babies, it is obviously important to know how these bone fractures are different from those caused by child abuse. Copper deficiency is not known to occur in babies unless they have another problem like prematurity, low birth weight, or poor food. In older people, extra copper in the diet helps keep the bones from getting thin but scientists need to fine tune the amount of copper that is needed to keep bones healthy because too much copper in the diet is also harmful. When people receive too much zinc in the diet, they can become copper deficient because the extra zinc crowds out the copper while it is being absorbed in the intestines. Regular amounts of boron in the diet also helps bones develop and grow normally, especially when there is not enough vitamin D in the diet. Boron may keep some older people from having severe arthritis in their joints. Scientists do not know all the causes of bone diseases and it is reasonable to assume that boron, copper, and other trace elements may be important in keeping bones healthy. The information in this review may stimulate further research on the importance of trace elements in bone health.
Technical Abstract: The review discusses boron and copper as examples of elements that are present in man in small or "trace", but important amounts. Copper deficiency is indicated by the presence of long bone abnormalities, psychomotor retardation, hypotonia, hypopigmentation, prominent scalp veins in palpable periosteal depressions, pallor, sideroblastic anemia resistant to iron treatment, vacuolated erythroid and myeloid cells in bone marrow, hepatosplenomegaly, neutropenia, and serum copper and ceruloplasmin concentrations below 6.28 mmol/L and 0.13 g/L, respectively. Unintentional copper depletion by over-zealous zinc therapy or chelation therapy as treatment for heavy metal poisoning or vascular disease is of obvious importance. Intentional copper chelation with drugs including penicillamine for treatment of abnormalities including Wilson's disease may over deplete copper stores. Signs of copper deficiency associated with perinatal stress are sometimes confused with unexplained fractures in infant non-accidental injury that are sometimes manifest in the battered child syndrome. Boron is beneficial for mineral, vitamin D, insulin, and energy substrate metabolism and immune function in animals and humans. In particular, dietary boron has physiological effects beneficial to bone growth and maintenance. Further characterization of the metabolic roles of these and other trace elements related to bone metabolism seems an extremely prudent endeavor because of the probable association of several refractory bone diseases with trace and ultratrace elements nutriture. |
<urn:uuid:2f56d3f7-bfe7-4cd3-85d9-31a9b9a13f86> | seed | Study uncovers key to killer flu response
Cell storms US researchers say they have uncovered the mechanism that causes the body to mount a severe, sometimes fatal, response to the flu.
Their discovery could lay the foundation for new treatments for a broad range of infectious and autoimmune conditions including pandemic flu, SARS, multiple sclerosis and HIV.
The researchers, from The Scripps Research Institute, studied a phenomenon called cytokine storms.
Cytokines are proteins that regulate the body's immune response to infection. An overproduction of cytokines causes the body's immune system to go into overdrive and attack itself. This can cause extensive inflammation and tissue damage.
Cytokine storms are thought to be responsible for many deaths in the 1918 flu pandemic, as well as in more recent outbreaks of bird and swine flu.
Researchers previously believed these storms were initiated by virus-infected cells lining the lungs and nasal passages.
But the study findings, reported in the journal Cell, indicates these storms are caused by cytokines released by cells that line blood vessels and lymphatic tissue in the lungs.
"Most people who have been focusing on viral infection have been focusing on the cells lining the air side of the lungs - the respiratory epithelium," says senior author Dr Hugh Rosen.
"What we've shown is that … there is amplification of the events of the cells lining the small blood vessels of the lungs that amplifies the immune response."
Using mice infected with strains of human influenza A and H1N1 swine flu, they identified that a protein on the endothelial cells called a Sphingosine-1-phosphate receptor (S1P1) is essential for flu-associated cytokine storms.
"We have the first definitive proof that cytokine storms play a significant role in acute respiratory infections like influenza, before there's been an association," says study co-author Dr Michael Oldstone.
The research showed these storms could be prevented using a small molecule to block the S1P1 receptor.
"The fact that we could block a cytokine storm specifically with a small molecule in the endothelial cells indicates the value of the cytokine storm," says Oldstone.
These findings indicate that drugs that block the SIP1 receptors could be used alongside vaccinations to prevent and treat severe illness, says Rosen.
"By blunting the amplification of cytokines, you protect from the collateral damage induced by the immune response, but the host can still fight the infection … and generate long-term memory that provides the life-long effect of immunisation."
While phase 1 trials using some of the chemical compounds identified in the research have begun in people with multiple sclerosis, a lot more work needs to be done, says Rosen.
"We know what sort of chemical compounds can be helpful in these pathways, but it's a big step in knowing that and actually having compounds that are proven to be sufficiently safe in humans," he says.
The discovery could also help identify people who are more genetically susceptible to cytokine storms, adds Rosen.
Professor Andrew Lloyd, director of the Inflammation and Infection Research Centre at the University of New South Wales says the research is a "big leap forward".
"It's potentially opening a whole new avenue of treatment programs for humans with a range of infective and immunological disorders," says Lloyd, who was not involved in the research.
"This group may well have identified a critical step [in the immune system pathway] that could plausibly be targeted."
But Lloyd says the results are yet to be proven in the broader scheme of mouse models and human studies.
"This is a very contrived system in mice. It's not clear that the phenomena that they are interested in will recapitulate into humans, or will have relevance to other viruses.
"But there is quite good plausibility that will be true." |
<urn:uuid:4e58ceb2-5751-4ea1-9059-50f7229a1a5a> | seed | Mevalonic aciduria (MVA) and hyperimmunoglobulinemia D syndrome (HIDS) represent the two ends of a clinical spectrum of disease caused by deficiency of mevalonate kinase (MVK), the first committed enzyme of cholesterol biosynthesis. At least 30 patients with MVA and 180 patients with HIDS have been reported worldwide. MVA is characterized by psychomotor retardation, failure to thrive, progressive cerebellar ataxia, dysmorphic features, progressive visual impairment and recurrent febrile crises. The febrile episodes are commonly accompanied by hepatosplenomegaly, lymphadenopathy, abdominal symptoms, arthralgia and skin rashes. Life expectancy is often compromised. In HIDS, only febrile attacks are present, but a subgroup of patients may also develop neurological abnormalities of varying degree such as mental retardation, ataxia, ocular symptoms and epilepsy. A reduced activity of MVK and pathogenic mutations in the MVK gene have been demonstrated as the common genetic basis in both disorders. In MVA, the diagnosis is established by detection of highly elevated levels of mevalonic acid excreted in urine. Increased levels of immunoglobulin D (IgD) and, in most patients of immunoglobulin A (IgA), in combination with enhanced excretion of mevalonic acid provide strong evidence for HIDS. The diagnosis is confirmed by low activity of mevalonate kinase or by demonstration of disease-causing mutations. Genetic counseling should be offered to families at risk. There is no established successful treatment for MVA. Simvastatin, an inhibitor of HMG-CoA reductase, and anakinra have been shown to have beneficial effect in HIDS.
Disease name and synonyms
Mevalonic aciduria (MVA, OMIM 251170).
Hyperimmunoglobulinemia D and periodic fever syndrome; Periodic fever, Dutch type (HIDS, OMIM 260920).
Definition and diagnostic criteria
MVA is an autosomal recessively inherited disorder caused by deficiency of mevalonate kinase (MVK; E.C. 126.96.36.199; ATP:(R)-mevalonate 5-phosphotransferase) and identified as the first defect in cholesterol biosynthesis (Figure 1) by Hoffmann et al. in 1986 . Mutations in the MVK gene and reduced activity of MVK have been identified as underlying cause of both MVA and HIDS syndrome.
Figure 1. Pathway of cholesterol biosynthesis, showing the defect in mevalonate kinase (MVK) deficiency.
MVA is caused by homozygosity or compound heterozygosity for disease-causing mutations in the MVK gene, which has been localized to chromosome 12q24 . MVA is biochemically characterized by accumulation of mevalonic acid and mevalonolactone.
The diagnosis of MVA should be suspected in patients with mild dysmorphic features, progressive cerebellar ataxia, psychomotor retardation, failure to thrive, hepatosplenomegaly and recurrent febrile episodes. Uveitis, retinitis pigmentosa and cataracts, as well as myopathy may develop in childhood and adolescence.
HIDS is clinically characterized by recurrent fever episodes starting in infancy and associated with lymphadenopathy, arthralgia, gastrointestinal problems and skin rashes.
A subgroup of HIDS patients may also develop neurological abnormalities of varying degree, such as mental retardation, ataxia, ocular symptoms and epilepsy, a finding that confirms the existence of a continuous spectrum between MVA and HIDS .
The diagnosis is established by the detection of elevated excretion of mevalonic acid in urine (MVA) or increased immunoglobulins (Ig) D and A in combination with elevated excretion of mevalonic acid (HIDS). The diagnosis is confirmed by demonstration of deficient MVK enzyme activity or by identification of two disease-causing mutations in the MVK gene.
The constellation of congenital malformations, hepatosplenomegaly, cholestatic liver disease, lymphadenopathy, anemia, severe failure to thrive and developmental retardation, which is found in severely affected MVA patients might suggest chromosomal aberrations or congenital infections. When hematological abnormalities such as anemia, leukocytosis, thrombocytopenia and abnormal blood cell forms predominate, myelodysplastic syndromes may be suspected. Moderately affected MVA patients may be classified among those with psychomotor retardation, myopathy and ataxia.
Recurrent crises from infancy of fever, diarrhea and mucocutaneous manifestations might suggest infectious or autoimmune disease . The development of uveitis in some patients parallels that seen in juvenile rheumatoid arthritis . If developmental delay and neurological symptoms are neither present nor prominent, the differential diagnosis is likely to focus within the group of auto-inflammatory disorders. This group consists of other inherited syndromes: familial Mediterranean fever (FMF); TNF receptor-associated periodic syndrome (TRAPS); familial cold autoinflammatory syndrome/Muckle-Wells syndrome/chronic infantile neurological cutaneous and articular syndrome (FCAS/MWS/CINCA) and periodic fever, aphthous ulcers, pharyngitis, adenitis (PFAPA).
MVA is a rare disease. So far, approximately 30 patients have been reported. HIDS seems to be more common. In 2001, the number of reported HIDS patients was about 180 and more patients have been identified since.
For MVA, seven mutations have been identified in 10 out of 20 known patients . Most of these mutations cluster in the C-terminal region of the protein.
Most patients with HIDS are compound heterozygotes for missense mutations in the MVK gene. One mutation, V337I, is present in more than 80% of patients . This mutation primarily affects maturation (folding) of the protein resulting in temperature-sensitive expression of MVK in vivo . In HIDS patients, MVK may have a residual activity of 5%–15%. In contrast, no residual activity is present in MVA patients .
MVA shows considerable clinical heterogeneity. Severely affected patients present from birth with congenital malformations such as microcephaly, dolichocephaly and wide irregular fontanels, as well as low set and posteriorly rotated ears, downslanted palpebral fissures, blue sclerae, and central cataracts (Figure 2). Cholestatic liver disease may be present, and patients may die from recurrent septicemia . Stillbirths with skeletal malformations have been observed in affected families, possibly resulting from the same genetic defect. Cardinal manifestations from late infancy include mild to severe psychomotor retardation, recurrent crises (fever, vomiting and diarrhea), failure to thrive, hypotonia and myopathy. Sometimes hematological abnormalities predominate with normocytic hypoplastic anemia, leukocytosis, thrombocytopenia and abnormal blood cell forms , leading to misdiagnoses of congenital infection or myelodysplastic syndromes.
Figure 2. A patient with mevalonic aciduria at the age of 21 months displaying the characteristic facial dysmorphism.
After preschool age, short stature, ataxia due to a progressive cerebellar atrophy and ocular involvement with uveitis, cataracts and tapetoretinal degeneration become predominant findings, and can be the major manifestations in milder cases [3-5,12].
Most patients suffer from frequent crises characterized by fever, vomiting and diarrhea. These episodes appear to be noninfectious in origin, and are often accompanied by arthralgia, subcutaneous edema and a morbilliform rash. Two patients developed uveitis, which worsened during crises. In childhood, episodes occur as often as 25 times per year, lasting in average 4 to 5 days. Laboratory investigations reveal elevated acute phase reactants (erythrocyte sedimentation rate, C-reactive protein, leukocytosis) and elevated immunoglobulins, including IgA, IgE and especially IgD. Anemia, elevations of creatine kinase (CK) and transaminases are present in the more severely affected patients, and worsen during crises. Over the years, the severity and the frequency of the attacks decline.
Hyperimmunoglobulinemia D syndrome
In HIDS, the clinical picture is dominated by recurrent febrile attacks that usually start before the end of the first year of life . The fever lasts 4 to 6 days and can be provoked by vaccination, minor trauma, surgery or stress. It is usually associated with abdominal pain, vomiting, diarrhea and cervical lymphadenopathy. Other common symptoms include hepatosplenomegaly, headache, arthralgia and rashes. Occasionally, patients present with oral and vaginal aphthous ulcers. After the attack, the patients are free of symptoms, although skin and joint symptoms disappear slowly . Most patients display neither malformations nor neurological abnormalities. However, a subgroup of adult patients also develop neurological abnormalities of varying degree, such as mental retardation, ataxia, ocular symptoms and epilepsy, reflecting the existence of a continuous spectrum between MVA and HIDS .
Generally, the metabolic abnormalities seen in MVA are not those suggestive of an inherited organic aciduria. There is no episodic metabolic decompensation, hypoglycemia, metabolic acidosis, ketosis or hyperammonemia. The key for diagnosis is the elevated level of mevalonic acid in the urine, plasma and cerebrospinal fluid, which can be detected through organic acid analysis . However, in patients with a mild form of MVA and especially in HIDS patients, elevations measured by routine gas chromatography/mass spectrometry may only be found during febrile attacks. The sensitivity of general organic acid analysis is inadequate for recognizing the very low concentrations of mevalonic acid present in control urine. Even moderate, but definitely pathological, elevations can remain below the detection limit , and must be verified by isotope dilution mass spectrometry . As the absolute level of mevalonic acid is always elevated in patients with MVK deficiency, samples from patients with a suspected MVA deficiency should undergo a sensitive measurement of mevalonic acid by stable isotope dilution analysis to detect even slight abnormalities. The diagnosis of MVA should be confirmed by mutational analysis or by a radiometric assay of MVK in white blood cells or cultured fibroblasts [16,17]. Urinary excretion of leukotriene E4 is elevated in most patients, with a positive linear correlation with increased mevalonic acid excretion .
HIDS is diagnosed on the basis of characteristic clinical findings and continuously high IgD values (more than 100 IU/ml). However, IgD may be normal in patients under three years of age . Consistently normal IgD levels were found in two patients with typical clinical findings and genotype for the syndrome [3,20]. More than 80% of patients have, in addition, high IgA levels [19,21]. During febrile episodes, urinary mevalonate concentrations were found to be significantly elevated in patients with at least one mutation in the MVK gene, but slight elevations were also detected between the fever attacks . Therefore, specific sensitive determination of mevalonic acid, mutational analysis and determination of enzyme activity should be performed in all cases with suggestive clinical symptoms and normal IgD levels.
Genetic counseling and prenatal diagnosis
Genetic counseling should be offered to families at risk of MVA. As MVA is an autosomal recessive disorder, the risk for future pregnancies is 25% for families who already have a child with MVA.
Prenatal diagnosis of an affected fetus is possible by stable isotope-dilution gas chromatography/mass spectrometry, by determination of MVK activity in cultured amniocytes and biopsied chorionic villus [1,12,14,17], and by mutational analysis in informative families. In affected pregnancies, elevated levels of mevalonic acid have been detected in maternal urine [1,12,14]. Significant elevations of mevalonic acid have been detected in autopsied tissues (including lymph nodes, adrenals, ovaries, spleen, liver and brain) from an affected fetus, .
Prenatal diagnosis is usually not considered to be appropriate for HIDS.
Management including treatment
There is no established therapeutic regime for patients with MVA. Dietary supplementation of cholesterol may reduce the frequency and severity of febrile attacks in some mildly affected patients, but may further compromise more severely affected patients . An experimental trial with lovastatin in two patients with MVA resulted in clinical decompensation manifested by fever, acute myopathic changes, highly elevated creatine kinase activity, and worsened ataxia, diarrhea and vomiting. Intervention with corticosteroids (prednisone 2 mg/kg per day) was highly beneficial during clinical crises, with resolution of the crises within 24 hours. Additional long-term administration of ubiquinone-50, together with vitamin C and vitamin E, appeared to stabilize the clinical course and improve somatic and psychomotor development. The rationale is to correct the ubiquinone-50 deficiency and to increase the level of free radical scavengers .
Treatment of HIDS is difficult and largely supportive. Various standard anti-inflammatory drugs (including colchicine, non steroidal anti-inflammatory drugs (NSAIDs), steroids and thalidomide) have failed to suppress the attacks. Despite the severe side effects of 3'-hydroxy-3'-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors in patients with classic MVA, a recently completed study showed a reduced excretion of mevalonic acid in all patients, a decreased number of febrile days in most of the patients with HIDS, and no side effects during simvastatin treatment . Similarly, a beneficial effect of anakinra (a recombinant interleukin-1 receptor antagonist) was described in one patient .
In early-onset multisystemic MVA, the prognosis is poor, with about half of patients succumbing in infancy or early childhood . Mildly affected patients will develop short stature, progressive myopathy and, possibly, visual impairment due to uveitis, cataracts and tapetoretinal degeneration. The severity and frequency of the febrile attacks decline with age. In general, HIDS is considered to be a relatively benign condition. However, life expectancy may be reduced in some patients due to severe infections or the development of renal amyloidosis .
It is still not known how the deficiency of MVK is related to the inflammatory periodic fever syndrome. Elevations of IgD, IgA and urinary leukotriene E4 excretion are probably secondary to stimulation of the immune system .
Figure 2 is reproduced with permission from Haas et al. 2001, © Georg Thieme Verlag KG
N Engl J Med 1986, 314:1610-1614. PubMed Abstract
Hoffmann GF, Charpentier C, Mayatepek E, Mancini J, Leichsenring M, Gibson KM, Divry P, Hrebicek M, Lehnert W, Sartor K, et al.: Clinical and biochemical phenotype in 11 patients with mevalonic aciduria.
Pediatrics 1993, 91:915-921. PubMed Abstract
Houten SM, Koster J, Romeijn GJ, Frenkel J, Di Rocco M, Caruso U, Landrieu P, Kelley RI, Kuis W, Poll-The BT, Gibson KM, Wanders RJA, Waterham HR: Organisation of the mevalonate kinase (MVK) gene and identification of novel mutations causing mevalonic aciduria and hyperimmunoglobulinaemia D and periodic fever syndrome.
Cuisset L, Drenth JP, Simon A, Vincent MF, van der Velde Visser S, van der Meer JW, Grateau G, Delpech M: Molecular analysis of MVK mutations and enzymatic activity in hyper-IgD and periodic fever syndrome.
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Frenkel J, Houten SM, Waterham HR, Wanders RJ, Rijkers GT, Duran M, Kuijpers TW, van Luijk W, Poll-The BT, Kuis W: Clinical and molecular variability in childhood periodic fever with hyperimmunoglobulinaemia D.
Hoffmann GF, Sweetman L, Bremer HJ, Hunneman DH, Hyanek J, Kozich V, Lehnert W, Nyhan WL, Speidel I, Trefz FK, et al.: Facts and artefacts in mevalonic aciduria: development of a stable isotope dilution GCMS assay for mevalonic acid and its application to physiological fluids, tissue samples, prenatal diagnosis and carrier detection.
Adv Pediatr 2000, 47:1-53. PubMed Abstract
Gibson KM, Lohr JL, Broock RL, Hoffmann G, Nyhan WL, Sweetman L, Brandt IK, Wappner RS, Bader PI: Mevalonate kinase in lysates of cultured human fibroblasts and lymphoblasts: kinetic properties, assay conditions, carrier detection and measurement of residual activity in a patient with mevalonic aciduria.
Enzyme 1989, 41:47-55. PubMed Abstract
Houten SM, Kuis W, Duran M, de Koning TJ, van Royen-Kerkhof A, Romeijn GJ, Frenkel J, Dorland L, de Barse MM, Huijbers WA, Rijkers GT, Waterham HR, Wanders RJ, Poll-The BT: Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome.
Stojanov S, Lohse P, Lohse P, Hoffmann F, Renner ED, Zellerer S, Kery A, Shin YS, Haas D, Hoffmann GF, Belohradsky BH: Molecular analysis of the MVK and TNFRSF1A genes in patients with a clinical presentation typical of the hyperimmunoglobulinemia D with periodic fever syndrome: a low-penetrance TNFRSF1A variant in a heterzygous MVK carrier possibly influences the phenotype of hyperimmunoglobulinemia D with periodic fever syndrome or vice versa.
D'Osualdo A, Picco P, Caroli F, Gattorno M, Giacchino R, Fortini P, Corona F, Tommasini A, Salvi G, Specchia F, Obici L, Meini A, Ricci A, Seri M, Ravazzolo R, Martini A, Ceccherini I: MVK mutations and associated clinical features in Italian patients affected with autoinflammatroy disorders and recurrent fever.
Eur J Hum Genet 2004, 12:1-7. Publisher Full Text |
<urn:uuid:3322ac82-f11b-44b9-aa12-596a8d1ebb39> | seed | “Function follows form” might have been written to describe proteins, as the M. C. Escher-esque folds and twists of nature’s workhorse biomolecules enables each to carry out its specific responsibilities. Technology’s workhorse for determining protein structures is X-ray protein crystallography, in which a beam of x-rays sent through a crystallized protein is scattered by the protein’s atoms, creating a diffraction pattern of dots that can be reconstructed by computer into a 3D model
X-ray crystallography of proteins yields structural images that resemble the artwork of M.C. Escher. A combination of the PHENIX and Rosetta programs can help refine these structural images, making the best of available data.
While synchrotron radiation facilities, such as Berkeley Lab’s Advanced Light Source, have been a boon to the field of protein crystallography, providing increasingly higher resolution structures over increasingly shorter time-spans, the technology is still a challenge. For some molecules, especially large molecular complexes, it is often only possible to obtain low-resolution experimental data, which means models are difficult to make and must be manually refined using computer modeling.
“Refinement of protein and other biomolecular structural models against low-resolution crystallographic data has been limited by the ability of current methods to converge on a structure with realistic geometry,” says Paul Adams, a bioengineer with Berkeley Lab’s Physical Biosciences Division and leading authority on x-ray crystallography, who, starting in 2000, has been leading the development of a highly successful software program called PHENIX (Python-based Hierarchical ENvironment for Integrated Xtallography) that automates crystallography data analysis.
Now, Adams and a team that included Nathaniel Echols in his research group, and Frank DiMaio with the research group of David Baker at the University of Washington, have developed a new method for refining crystallographic data that combines aspects of PHENIX with aspects of Rosetta, the most widely used software for the prediction and design of the three-dimensional structure of proteins and other large biomolecules.
The Rosetta program, which was originally developed by Baker and his research group, utilizes a detailed all-atom force field plus a diverse set of search procedures for the creation of its 3D models. PHENIX assembles 3D models atom-by-atom through the extraction of the best data from X-ray measurements. One of the most important components of PHENIX is “phenix.refine,” a program for improving these models against the X-ray data using maximum likelihood methods. It was this feature that was combined with Rosetta.
“Our new method integrates the Rosetta and PHENIX programs directly in a flexible framework that allows it to be adapted to a wide variety of different scenarios,” says Echols. “The main advantage of our method is that it can aggressively optimize models to fit the data and also present realistic geometry. In general, it has been difficult to come up with methods that handle both of these demands. As a result, crystallographers have either spent a lot of time fixing errors, or the published structures end up being of poor quality.”
Echols is one of two lead authors, along with DiMaio, of a paper in Nature Methods describing this work. The paper is titled “Improved low-resolution crystallographic refinement with Phenix and Rosetta.” In addition to Adams and Baker, other co-authors are Jeffrey Headd and Thomas Terwilliger. Adams and Baker are the corresponding authors.
Funding for this research was provided by the National Institutes of Health and the U.S. Department of Energy’s Office of Science. |
<urn:uuid:aa3da184-04f8-4a48-8d5e-7dcbca51a953> | seed | Status epilepticus: theoretical and clinical considerations
Jun 01, 2006
Two or more seizures without complete recovery of consciousness between seizures, or persistent seizure activity for more than 30 minutes constitute the definition of status epilepticus (SE) in human medicine (Treatment of Convulsive Status Epilepticus. JAMA 1993; 270:854-9).
Death during or immediately after seizures is thought to be due to a centrally induced respiratory failure in animal models (Graham, Lantos, Greenfield's Neuropathology, Vol. 1). Occasional fatal arrhythmias are also documented with SE.It is critical to be aware of the systemic complications and the extensive brain damage induced by SE. Metabolic acidosis, hypoxia, hypercapnia, hypoglycemia, hyperpyrexia, electrolyte disturbances incontinence, myoglobinuria, renal failure, respiratory failure and arrhythmias might accompany seizure activity (J. Sirven et al.: Management of Status Epilepticus; American Family Physician, 2003, Vol. 68, No. 3). All of these changes can be exaggerated in SE.
The epileptic brain damage is due to a so-called consumptive hypoxia. It is documented in human patients that during ictus there is an actual cerebral hyperperfusion with hypermetabolism of the epileptogenic areas in the brain. In spite of the hyperperfusion, the increased oxygen and glucose demand (required by the increased metabolic rate) overcomes the increased cerebral blood flow, and eventually leads to consumptive hypoxia with subsequent neuronal cell loss. Certain areas such as the hippocampus, selected laminas of the neocortex and the Purkinje layer of the cerebellum are more affected than others.
In cases of SE, systemic stabilization and cessation of the seizure activity can lead to successful outcomes. Small animal clinicians have long used diazepam, propofol, sodium pentobarbital and inhalation anesthesia to help manage SE. It is noteworthy that 24-hour EEG monitoring of human patients (after presumed successful treatment of their clinical seizure activity) demonstrate periodic discharges of seizure activity in about half of the patients.
In a recent article (S. Serrano et al.: "Use of Ketamine for the Management of Refractory Status Epilepticus in a Dog", J Vet Intern Med 2006:20:194-197) the authors achieved the cessation of seizures using bolus and constant-rate infusion (CRI) of ketamine in a dog with granulomatous meningoencephalomyelitis and SE that was refractory to IV diazepam and propofol.
According to the authors' explanation, ketamine antagonizes a certain ionotropic receptor subtype (the N-methyl-d-aspartic acid, NMDA). Activation of NMDA receptors during SE enhances the calcium influx and promotes subsequent cell death by a cascade of reactions (Graham, Lantos, Greenfield's Neuropathology, Vol. 1). The mitochondria become damaged by the heavy load of calcium, leading to superoxide generation that is toxic to the cell and the mitochondrial DNA. The nucleus and the cytoskeleton are also damaged by the calcium overload, and various toxic proteases (calpain), phospholipases become activated causing the formation of cytotoxic molecules.
Controversially, according to S. Serrano et al., excessive NMDA receptor antagonism can also be toxic, which could explain the ketamine neurotoxic effects on selected cortical neurons and Purkinje cells.
In conclusion, although there is not enough evidence for a clear recommendation regarding the use of ketamine in SE, NMDA receptor antagonism may deserve consideration in clinical research and selected clinical cases of refractory SE in veterinary medicine.
Dr. Beatrix Nanai is a resident of the European College of Veterinary Neurology/Neurosurgery at the Animal Emergency and Referral Center in Fort Pierce, Fla.
Dr. Ronald Lymann a graduate of The Ohio State University College of Veterinary Medicine. He completed a formal internship at the Animal Medical Center in New York City. Lyman is a co-author of chapters in the 2000 editions of Kirk's Current Veterinary Therapy XIII and Quick Reference to Veterinary Medicine. |
<urn:uuid:a587bb92-5d89-4dbf-8074-0b097e9aabdf> | seed | Swine Trichinella infection and geographic information system tools.
Disease transmission (Control)
Disease transmission (Research)
Trichinosis (Risk factors)
Geographic information systems (Usage)
Murrell, K. Darwin
|Publication:||Name: Emerging Infectious Diseases Publisher: U.S. National Center for Infectious Diseases Audience: Academic; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2008 U.S. National Center for Infectious Diseases ISSN: 1080-6040|
|Issue:||Date: July, 2008 Source Volume: 14 Source Issue: 7|
|Topic:||Event Code: 310 Science & research; 690 Goods & services distribution Advertising Code: 59 Channels of Distribution Computer Subject: Geographic information system; Company distribution practices|
|Product:||SIC Code: 7372 Prepackaged software|
|Geographic:||Geographic Scope: United States Geographic Code: 1USA United States|
Pastured pigs are vulnerable to Trichinella spiralis infection
through exposure to wild reservoir hosts. To evaluate the potential
impact of the expanding production of pork from pasture-raised pigs, we
mapped locations of T. spiralis occurrence and pastured-pig farms in the
United States. Twenty-eight farms were located within 50 km of previous
The incidence of Trichinella spiralis infection in humans and swine has declined markedly in North America over the past 20 years; however, sporadic outbreaks still occur (1,2). The importance of sylvatic reservoir hosts in the persistence of T. spiralis infection risk is well-documented, even in countries that have made substantial gains in controlling the infection in swine (2-5); T. spiralis infection has been recently demonstrated in foxes in Ireland, where no pig infections had been identified for 30 years, (6). The outdoor rearing of pigs is a major risk because of increased exposure to sylvatic and synanthropic hosts (2-10). Transmission of T. spiralis from infected farm pigs to synanthropic (e.g., rats, cats, raccoons) and local sylvatic animal populations also occurs (3,11).
Pastured-pig operations in the United States have experienced substantial growth in recent years. The number of pigs reared in organic livestock operations, which by law must pasture pigs for at least some part of the day, rose from 1,724 in 2000 to 10,018 in 2005 (12). An even larger number of pigs (>100,000) are now being reared nonorganically on pasture and marketed as "pastured, humane, or free-range" pigs. (See below for source of information.) Because of the sporadic occurrence and distribution of outbreaks, and the lack of routine monitoring, the impact of this increase on the risk for T. spiralis infection for pastured farm swine is unknown. We report the use of geographic information system (GIS) methods to locate potential high-risk foci to facilitate targeting of surveillance for domestic pig infections, similar to the recent study identifying areas of risk for fascioliasis (13).
Two Trichinella databases (All Hosts and Domestic Pig) were compiled by using literature published over the past 60 years (full list of references provided on request from [email protected]) and Trichinella isolate records from North America, maintained at the International Trichinella Reference Center in Rome (www.iss.it/site/ Trichinella). The All Hosts database contains records on T. spiralis infections in wildlife, including synanthropic species such as rats, cats, skunks, and foxes. The second database, Domestic Pig, contains records on T. spiralis from domestic pigs. The sylvatic species T. nativa and T. murrelli, which occur in North America, are not infective for pigs (Sus scrofa). T. pseudospiralis, which has low infectivity for pigs, has been reported only from a vulture and from a wild boar in North America, but because of the wide range of the former species (12,000-18,000 ha) and the location of wild boars >150 km from a known pasturedpig operation, we excluded this species from our analysis. When latitude and longitude data on host collection sites were not available, we approximated the locations using the coordinate points of the closest town to the collection site. From the 201 T. spiralis records that were collected, 54 were selected for mapping (37 wildlife hosts and 17 domestic pig infections). Other records were eliminated either because of vague descriptions of location or because they could not be confirmed as T. spiralis rather than a sylvatic species. The infected sylvatic hosts included black bear (Ursus americanus), raccoon (Procyon lotor), opossum (Didelphis virginiana), feral pig/wild boar (Sus scrofa), red fox (Vulpes vulpes), gray fox (Urocyon cinereoargenteus), feral cat (Felis catus), striped skunk (Mephitis mephitis), coyote (Canis latrans), and mink (Neovison vison). With the exception of black bears, these wild animals are potentially synanthropic hosts and transfer T. spiralis between the sylvatic and domestic habitats (2-5).
A third database was created for US farms that raise organic or nonorganically pastured swine. We obtained these data by searching the Internet using the keywords "pasture," "pork," and "organic" for farms producing and marketing pork through the Internet. The latitude/longitude coordinates from town and state data were determined by using the website www.zipinfo.com/search/zipcode.htm.
The databases were converted into map layers within ArcGIS (Environmental Systems Research Institute, Redlands, CA, USA). A basic political boundaries map served as the base map. The western United States is not shown in Figure 1 because the main areas with frequent reports of wild animal and domestic pig T. spiralis infections and a prominent pastured-pig industry are the Northeast/ Middle Atlantic and the central Midwest. Figure 2 shows an enlargement of the Midwest area to illustrate the ability to more precisely locate risk locations (county level). A GIS analysis, using a program in ArcGIS, was performed to measure the distance between pastured-pig farms and historical occurrences of T. spiralis in domestic pigs and wildlife. The program calculates a distance between each pastured-pig farm and the nearest T. spiralis point on the map and was run 3 times using the following variables: 1) T. spiralis in domestic pigs, 2) T. spiralis in wildlife, and 3) T. spiralis in both pigs and wildlife (Table).
[FIGURE 1 OMITTED]
Of the 332 pastured-pig farms mapped, 28 are located within 50 km of documented T. spiralis in domestic pigs or wildlife; 6 of these farms are within 50 km of locations with both pig and sylvatic T. spiralis infections. An additional 48 pastured-pig operations are within 100 km of T. spiralis infection locations.
Using GIS methods to analyze the risk for T. spiralis infection associated with the expansion of pastured-pig production, we identified farms that may be at high risk for the introduction of infection into pigs from reservoir hosts. We base this on the fact that the transmission of T. spiralis into sylvatic hosts from infected farms can lead to persistence in reservoir hosts (2,3) and remain a long-term threat to domestic pigs exposed to such hosts in a pasture/ dry lot environment (2-11). The number of pastured-pig farms and records of T. spiralis infections are highest in the Northeast and Midwest. Figure 2 demonstrates the ability through map enlargement to identify associations at the local level. In Illinois and Indiana, at least 10 farms within 50 km of previous T. spiralis infection in pigs or sylvatic hosts could be identified at the county level. The distances between pastured farms and the locations with recorded foci of T. spiralis in wild animals or domestic pigs used in the analysis (Table) are based on the general home ranges for the host species (14). For example, raccoons may range up to 3-10 [km.sup.2], red foxes 2-10 [km.sup.2] (with male dispersal up to 80 [km.sup.2]), and coyotes up to 5-70 [km.sup.2].
[FIGURE 2 OMITTED]
These findings should increase the awareness of pastured-pig producers and state veterinary and public health agencies of this potential problem. Targeted surveillance and management prevention programs need to be established in high-risk areas. The use of GIS tools could also help researchers to conveniently locate transmission loci to investigate the measures needed to prevent infection of outdoor-reared pigs. The database we created on pastured-pig operations is undoubtedly an underestimate of risk because of a lack of a national centralized reporting system for these rearing systems. Furthermore, the infection records are not from a national prevalence survey, which is lacking, but were complied from publications of local surveys and outbreaks (convenience samples). The bias from this method does not, we believe, detract from the objective to introduce the use of GIS tools for identifying foci with potential for T. spiralis transmission in outdoor pig-rearing systems. Identification of such foci would provide the opportunity to investigate transmission among wild animals and pigs in agro-ecosystems and the variables that influence transmission, such as climate, pig farm size, herd size, and pig exposure.
This work was carried out in the Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences.
At the time of this study, Dr Burke was a student in the Master's in Public Health program at the Uniformed Services University of the Health Sciences. Currently, she is a laboratory animal medicine resident at the US Army Medical Research Institute for Infectious Diseases at Ft. Detrick, Maryland.
(1.) Roy SL, Lopez AS, Schantz PM. Trichinellosis surveillance--United States, 1997. MMWR Surveill Summ. 2003;52:1-8.
(2.) Pozio E, Murrell KD. Systematics and epidemiology of Trichinella. Adv Parasitol. 2006;63:367-439. DOI: 10.1016/S0065-308X (06)63005-4
(3.) Murrell KD, Stringfellow F, Dame JB, Leiby DA, Duffy C, Schad GA. Trichinella spiralis in an agricultural ecosystem. II. Evidence for natural transmission of Trichinella spiralis spiralis from domestic swine to wildlife. J Parasitol. 1987;73:103-9. DOI: 10.2307/3282352
(4.) Worley DE, Seesee FM, Zarlenga DS, Murrell KD. Attempts to eradicate trichinellosis from a wild boar population in a private game park (USA). In: Campbell WC, Pozio E, Bruschi F, editors. Trichinellosis. Proceedings of the Eighth International Conference on Trichinellosis. Ovieto, Italy. Rome: Instituto Superiore di Sanita Press; 1994. p. 611-6.
(5.) Doby PB, Murrell KD. Illinois Trichinellosis Control Program. In: Tanner CE, Martinez-Fernandez AR, Bolas-Fernandez F, editors, Trichinellosis. Madrid: Consejo Superior de Investigationes Cientificas Press; 1989. p. 432-8.
(6.) Rafter P, Marucci G, Brangan P, Pozio E. Rediscovery of Trichinella spiralis in red foxes (Vulpes vulpes) in Ireland after 30 years of oblivion. J Infect. 2005;50:61-5. DOI: 10.1016/j.jinf.2004.02.004
(7.) Gamble HR, Boireau P, Kockler K, Kapel CMO. Prevention of Trichinella infection in the domestic pig. In: Dupouy-Camet J, Murrell KD, editors. FAO/WHO/OIE guidelines for the surveillance, management, prevention and control of trichinellosis. Paris: World Organisation for Animal Health; 2007. p. 99.
(8.) Gamble HR, Brady RC, Bulaga LL, Berthoud CL, Smith WG, Detweiler LA, et al. Prevalence and risk association for Trichinella infection in domestic pigs in the northeastern United States. Vet Parasitol. 1999;82:59-69. DOI: 10.1016/S0304-4017(98)00267-2
(9.) Nockler K, Kapel CMO. Detection and surveillance for Trichinella. In: Dupouy Camet J, Murrell KD, editors. FAO/WHO/OIE guidelines for the surveillance, management, prevention and control of trichinellosis. Paris: World Organisation for Animal Health; 2007. p. 69-97.
(10.) van der Giessen J, Fonville M, Bouuknegt M, Langelaar M, Vollema A. Seroprevalence of Trichinella spiralis and Toxoplasma gondii in pigs from different housing systems in The Netherlands. Vet Parasitol. 2007;148:371-4. DOI: 10.1016/j.vetpar.2007.06.009
(11.) Leiby DA, Duffy CH, Murrell KD, Schad GA. Trichinella spiralis in an agricultural ecosystem: transmission in the rat population. J Parasitol. 1990;76:360-4. DOI: 10.2307/3282667
(12.) United States Department of Agriculture. Economic Research Service (ERS), Data Sets, Organic Production. Table 5: certified organic livestock. Data on cows, pigs, sheep, chickens and other poultry, by state, 1997 and 2000-2005 [cited 2007 Mar 21]. Available from http://www.ers.usda.gov/Data/Organic/index.htm#tables
(13.) Tum S, Puotinen ML, Skerrat LF, Chan B, Sothoen S. A geographic information system for mapping the risk of fascioliasis in cattle and buffaloes in Cambodia. Vet Parasitol. 2007;143:364-7. DOI: 10.1016/j.vetpar.2006.08.033
(14.) Wilson DE, Ruff S. The Smithsonian book of North American mammals. Washington: Smithsonian Institution Press; 1999.
Address for correspondence: K. Darwin Murrell, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD 20814, USA; email: [email protected]
Robin Burke, * Penny Masuoka, * and K. Darwin Murrell *
* Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
Table. Distances of current pastured-pig operations to locations with past occurrences of Trichinella spiralis in domestic pigs or wildlife, United States Distance to Farms near Farms near Farms near T. spiralis locations of locations of locations infection T. spiralis T. spiralis of T. spiralis Total site and in domestic in wildlife in both pigs farms, km pigs and wildlife 19-50 6 16 6 28 51-100 7 21 20 48
|Gale Copyright:||Copyright 2008 Gale, Cengage Learning. All rights reserved.| |
<urn:uuid:048bb20b-8923-4f3f-a3d1-e6c55376d992> | seed | Microbes have ruled the earth for more than a billion years; comparatively, we humans are just upstarts. Yet since the invention of penicillin in 1940, we have inflicted a crippling blow on many types of bacteria that make us ill or kill us.
But the bugs have struck back by activating DNA that is prone to errors when it replicates. This increases the chance that mutations will develop to fend off the mortal threat posed by antibiotics. In 2005, biochemist Floyd Romesberg of the Scripps Research Institute, near San Diego, announced that his lab had discovered a gene called LexA that switches on the error-prone DNA, enabling the microbe to mutate rapidly.
Shortly before this announcement, Romesberg presented some startling findings during a meeting at the institute I cofounded, the BioAgenda Institute. Romesberg, a short, intense man with a graying beard and an ability to explain complex ideas to nonscientists, told us that his lab had learned how to turn off LexA. Several major biotechnology figures at the meeting said to me, “This is huge.” At the time, several top-tier venture-capital firms were vying for Romesberg’s attention in hopes of starting a company. Ned David was one of the lucky cofounders who later named the company Achaogen–“achao” means “against chaos” in Latin.
Now Romesberg has announced the discovery of a molecule that inhibits LexA‘sability to cause mutations; it was found after the lab screened more than 100,000 possible compounds. The molecule also slips easily into a bacterial cell, which is critical to creating an effective tool to zap the bugs.
This new mutation killer does not prevent bacterial infections. Taken in combination with antibiotics, it would prevent the bugs from mutating in response to the antibiotics, thereby preventing resistant strains from developing. The drug could also be used to restore the effectiveness of older antibiotics that have been rendered almost useless by bacterial resistance.
Romesberg’s lab is also looking into ways to shut down mutations that cause cancer, as well as mutations in general. His interest lies in how evolution uses mutations to effect change and in how to influence and manipulate these evolutionary processes. Part of his lab focuses on using nucleotides and amino acids (beyond the 4 nucleotides and 20 amino acids found in nature) that he and others have created.
This is heady stuff, and I’ll write more about it in a future blog.
As the Borg used to say on Star Trek, “Resistance is futile!”–that is, until the bugs that have for so long ruled the earth figure out their next countermove. In the meantime, we can savor our victory.
Service, Robert F., “Resistance Is Futile,” ScienceNOW Daily News 28 March 2007 |
<urn:uuid:3f8aade7-eb36-459c-992d-12cc2df74209> | seed | During the third year of life, most toddlers gain about 4 pounds (1.8 kilograms) and grow about 2 to 3 inches (5 to 8 centimeters).
They're extremely active and mobile, and learning in very physical ways. They're running around and exploring their world, and picking up new skills, like kicking a ball and riding a tricycle.
Your toddler's appetite may fluctuate greatly now, which is common. It is also common for some toddlers to get stuck on one food. Food "jags" usually don't last long if you don't accommodate them. To build a foundation of healthy eating habits, keep serving a variety of nutritious foods and allow your child to decide what and how much to eat from the healthy foods you offer.
Although kids come in all shapes and sizes, a healthy child should continue to grow at a regular pace. The doctor will measure and weigh your child at routine checkups and plot the results on a growth chart. This allow the doctor to track your child's growth over time and spot trends that need attention.
Helping Kids Grow
Normal growth — supported by good nutrition, adequate sleep, and regular exercise — is one of the best overall indicators of a child's good health. But your child's growth pattern is largely determined by genetics. Pushing kids to eat extra food or greater than recommended amounts of vitamins, minerals, or other nutrients will not increase their height.
Malnutrition severe enough to affect growth rate is uncommon today in the United States and other developed countries unless a child has an associated chronic illness or disorder.
At the Doctor's Office
Despite data collected for growth charts, "normal" heights and weights are difficult to define. Shorter parents, for instance, tend to have shorter kids, whereas taller parents tend to have taller kids.
Although you may worry if your child isn't as tall as his or her peers or weighs more, the more important question is whether your child is continuing to grow at a normal rate. If, for instance, your child's growth rate had been normal but has recently slowed, the doctor may track your child's measurements over a few months to see whether this is a possible health problem or just a variation of normal.
Most kids who are growing at or below the 5th percentile line on the growth chart are usually following one of these two normal variant growth patterns:
Familial (genetic) short stature. These kids have inherited genes for short stature from their parents. Usually one or both parents, and often other relatives, are short. Although they are shorter than average, they grow at a normal rate and are otherwise healthy, showing no symptoms of medical problems that can affect growth. They generally enter puberty at an average age and reach a final adult height similar to that of their parents. In general, no treatment is recommended or known to be effective in significantly increasing their final adult height.
Constitutional growth delay (delayed puberty). Although they are usually of average size in early infancy, these kids undergo a period of slower-than-average growth between 6 months and 2 years of age, causing them to fall to the 5th percentile or lower on the growth chart. After about age 2 or 3 years, kids with constitutional growth delay will grow at a normal childhood rate until they reach puberty and undergo a growth spurt at a later age than most other teens. Because they start puberty later, they will continue to grow after most teens have stopped, thus "catching up" to their peers in final adult height. Usually, there's a family history of this kind of growth pattern, and in general, there's no need for treatment.
If your child is growing too slowly, your doctor might order tests to determine whether this is related to a medical or genetic condition that would interfere with growth.
Be sure to discuss any concerns you have about your child's growth or development with your doctor. |
<urn:uuid:db7348a1-068a-48bc-ad30-700e23531691> | seed | Sickle-cell anemia (SCA) is an inherited condition in which some of the subject’s red blood cells contain an abnormal form of hemoglobin, the molecule that carries oxygen to the body's tissues.
Normal blood cell (left), and sickled blood cell (right).
Recent research by an interdisciplinary team of investigators including Professor Michael C.K. Khoo of the USC Viterbi School of Engineering's Department of Biomedical Engineering has found increasing evidence that autonomic nervous system (ANS) activity has a distinct pattern in SCA patients, which may be involved in precipitating these strokes.
Dr. Khoo has worked with his former graduate student, Suvimol Sangkatumvong, as well as Drs. Thomas Coates, John Wood and Herbert Meiselman of the USC Keck School of Medicine and Children’s Hospital Los Angeles on the study, which involved a number of patients of different ages diagnosed with SCA.
Since low oxygen levels in the blood are known to predispose to VOC, the Viterbi-Keck team’s experimental procedure compared the pattern of heart rate response of SCA under these conditions to the pattern in normal controls. These responses are controlled by the autonomic nervous system (ANS), an involuntary, unconscious control system that regulates body functions such as salivation, heartbeat, perspiration, respiration, and others.
For the experiment, which was supervised by Children’s Hospital staff, experimenters had SCA subjects take five deep breaths of nitrogen, filling their lungs but not putting oxygen into their blood.
In a preliminary safety check, none of the SCA subjects showed any significant short- or long-term results from the nitrogen inhalation. But careful comparison of their reactions revealed significant differences between the SCA subjects and controls. The ANS reaction, which the investigators deduced from the heart rate and breathing patterns by using a computational model, was substantially more exaggerated in the SCA group.
Another observation from the study involved sighing, technically defined as taking a breath twice as deep as the average breath, within two minutes after a stimulus. For each sigh, the team carefully measured heart rate and blood flow to the finger, looking for subtle changes in pattern compared to the control group.
Professor Michael C.K. Khoo
Khoo and his colleagues hope to further pursue the research in order to develop ways to use the insight to refine treatment techniques. “While there is no outright cure for sickle cell disease,” he says, "there are two major forms of therapeutic interventions that can lower the probability of VOC."
One intervention is administration of a drug, hydroxyurea. The other is blood transfusion to reduce the percentage of sickled cells. “What we're trying to do is to determine reliable biomarkers of the vaso-occlusive crises - and these biomarkers should also provide feedback as to how we can optimize the treatments. Our next steps are indeed to determine which are the most reliable biomarkers and how we can use them to optimize therapy.” |
<urn:uuid:b30dd0f7-3092-4ccb-b22f-0696a224e0a4> | seed | Lesson 1 Glossary
Important terms from Lesson 1 defined.
Escherichia coli (E. coli)
A rod-shaped bacterium belonging to the same family as Salmonella. E. coli is of the coliform group, which are organisms associated with the intestinal tract flora. Presence of coliforms is usually an indication of unsanitary handling or processing procedures.
The sickness resulting from eating food contaminated with either bacterial toxins or by certain bacteria in the food, often resulting in vomiting, diarrhea and prostration. Food-borne diseases are most often caused by several species of bacteria, although viruses, parasites, amoebas and other biological as well as chemical agents may be responsible. Food poisoning would include illness caused by naturally poisonous foods, like certain wild mushrooms, or from chemical contaminants in the food.
Food Poisoning Outbreak
An occurrence of food poisoning that involves many individual cases of food-borne illness.
To process milk so that the fat globules are so finely divided and emulsified that the cream does not separate on standing.
French chemist and bacteriologist who lived from 1822-95. He showed in 1857 that the souring of milk was due to the growth of organisms in it. Around 1860 he performed experiments using heat to destroy undesirable microorganisms in beer and wine. Heating (pasteurization) to remove undesirable organisms was introduced commercially in 1867.
Any microscopic animal or plant-like organism including bacteria, yeasts, viruses and single-celled algae.
The controlled heating of a food to destroy all pathogenic microorganisms.
The particular requirements for pasteurization are designed to kill Coxiella burnetii, the most heat-resistant pathogenic organism commonly associated with cow's milk.
Any microorganism that can cause disease. Salmonella is always considered a pathogenic microorganism. E. coli is considered an opportunistic pathogen. It is not always pathogenic, but given the opportunity, it can cause food-borne illness.
A group of organisms named after a U.S. veterinarian, D.E. Salmon. There are over 2,000 species within the genus Salmonella that will infect man. These rod-shaped bacteria cause various diseases in man and animals, including typhoid fever and food poisoning. Salmonella food poisoning can result from eating undercooked chicken, raw eggs, or contaminated milk and dairy products.
Name given to a disease caused by various species or strains of salmonella. Characterized by fever, malaise and intestinal disorder. Salmonellosis can be deadly to the young, old or infirm.
The science and practice of effecting healthful and hygienic conditions. The process of cleaning to inactivate viable pathogenic microorganisms. Having a sanitary work bench does not mean that it is a sterile one.
A detailed description of the parts of the whole; statement or enumeration of particular requirements such as size, number, quality, performance, etc.
The process of eliminating all viable life forms; nothing is left living in a sterilized product. Commercial sterilization involves the destruction of all pathogenic microorganisms as well as more heat-resistant organisms that could grow inside the processed food package under normal conditions of distribution and room-temperature storage. The amount of heat a package must receive to achieve commercial sterility is much greater than in other heated foods (such as pasteurized milk) due to the high resistance of many spoilage bacteria and their spores. |
<urn:uuid:c1a8510b-13d8-4d0f-b182-315bd6fe3edc> | seed | The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites , . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many of ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome , . L35 is a basic protein of 60 to 70 amino-acid residues from the large (50S) subunit . Like many basic polypeptides, L35 completely inhibits ornithine decarboxylase when present unbound in the cell, but the inhibitory function is abolished upon its incorporation into ribosomes . It belongs to a family of ribosomal proteins, including L35 from bacteria, plant chloroplast, red algae chloroplasts and cyanelles. In plants it is a nuclear encoded gene product, which suggests a chloroplast-to-nucleus relocation during the evolution of higher plants .; GO: 0003735 structural constituent of ribosome, 0006412 translation, 0005622 intracellular, 0005840 ribosome. |
<urn:uuid:9fce570f-957b-474c-8c1e-30dd5074f4af> | seed | Allergic reactions (hypersensitivity reactions) are inappropriate responses of the immune system to a normally harmless substance.
Normally, the immune system—which includes antibodies, white blood cells, mast cells, complement proteins, and other substances—defends the body against foreign substances (called antigens). However, in susceptible people, the immune system can overreact when exposed to certain substances (allergens) in the environment, foods, or drugs, which are harmless in most people. The result is an allergic reaction. Some people are allergic to only one substance. Others are allergic to many. About one third of the people in the United States have an allergy.
Allergens may cause an allergic reaction when they land on the skin or in the eye or are inhaled, eaten, or injected. An allergic reaction can occur in several ways:
In many allergic reactions, the immune system, when first exposed to an allergen, produces a type of antibody called immunoglobulin E (IgE). IgE binds to a type of white blood cell called basophils in the bloodstream and to a similar type of cell called mast cells in the tissues. The first exposure may make people sensitive to the allergen but does not cause symptoms. When sensitized people subsequently encounter the allergen, the basophils and mast cells with IgE on their surface release substances (such as histamine, prostaglandins, and leukotrienes) that cause swelling or inflammation in the surrounding tissues. Such substances begin a cascade of reactions that continue to irritate and harm tissues. These reactions range from mild to severe.
Most allergic reactions are mild, consisting of watery and itchy eyes, a runny nose, itchy skin, and some sneezing. Rashes (including hives) are common and often itch. Hives (see Hives), also called urticaria, are small, red, slightly elevated areas of swelling (wheals) that often have a pale center. Swelling may occur in larger areas under the skin (called angioedema—see Angioedema). Swelling is caused by fluids leaking from blood vessels. Depending on which areas of the body are affected, angioedema may be serious. Allergies may trigger attacks of asthma.
Certain allergic reactions, called anaphylactic reactions (see Anaphylactic Reactions), can be life threatening. The airways can narrow (constrict), causing wheezing, and the lining of the throat and airways may swell, interfering with breathing. Blood vessels can widen (dilate), causing a dangerous fall in blood pressure.
Doctors first determine whether a reaction is allergic. They may ask whether the person has close relatives with allergies because a reaction is more likely to be allergic in such cases. Blood tests are sometimes done to detect a type of white blood cell called eosinophils. Eosinophils, although present in everyone are usually produced in greater numbers when an allergic reaction occurs.
Because each allergic reaction is triggered by a specific allergen, the main goal of diagnosis is to identify that allergen. Often, the person and doctor can identify the allergen based on when the allergy started and when and how often the reaction occurs (for example, during certain seasons or after eating certain foods).
Skin tests (see Skin tests) are the most useful way to identify specific allergens. Usually, a skin prick test is done first. Dilute solutions are made from extracts of pollens (of trees, grasses, weeds, or fungal spores), dust, animal dander, insect venom, foods, and some drugs. A drop of each solution is placed on the person's skin, which is then pricked with a needle. If the person is allergic to one or more of these substances, the person has a wheal and flare reaction, indicated by the following:
The skin prick test can identify most allergens. If no allergen is identified, a tiny amount of each solution can be injected into the person's skin (intradermal test). This type of skin test is more likely to detect a reaction to an allergen.
Before skin tests are done, people are asked to stop taking antihistamines and certain antidepressants called tricyclic antidepressants (such as amitriptyline) and monoamine oxidase inhibitors (such as selegiline). These drugs may suppress a reaction to the tests. Some doctors also do not test people who are taking beta-blockers because if such people have an allergic reaction, the consequences are more likely to be serious. In addition, beta-blockers may interfere with the drugs used to treat serious allergic reactions.
The allergen-specific serum IgE test is used when skin tests cannot be used—for example, when a rash is widespread. This test determines whether IgE in the person's blood binds to a specific allergen used for the test. If binding occurs, the person has an allergy to that allergen.
However, skin tests and the allergen-specific serum IgE test may not detect all allergies, and they sometimes indicate that people are allergic to an allergen when they are not (called a false-positive result).
Avoiding an allergen, if possible, is the best approach. Avoiding an allergen may involve the following:
Allergen immunotherapy (desensitization):
Because some allergens, especially airborne allergens, cannot be avoided, allergen immunotherapy, usually allergy shots or injections, can be given to desensitize people to the allergen. With allergen immunotherapy, allergic reactions can be prevented or reduced in number and/or severity. However, allergen immunotherapy is not always effective. Some people and some allergies tend to respond better than others.
Immunotherapy is used most often for allergies to pollens, house dust mites, molds, and venom of stinging insects. When people are allergic to unavoidable allergens, such as insect venom, immunotherapy helps prevent anaphylactic reactions (see Anaphylactic Reactions). Sometimes it is used for allergies to animal dander, but such treatment is unlikely to be useful. Immunotherapy for food allergies is being studied.
Immunotherapy is not used when the allergen, such as penicillin and other drugs, can be avoided. However, if people need to take a drug that they are allergic to, immunotherapy, closely monitored by a doctor, can be done to desensitize them.
In immunotherapy, tiny amounts of the allergen are usually injected under the skin. The dose is gradually increased until a dose adequate to control symptoms (maintenance dose) is reached. A gradual increase is necessary because exposure to a high dose of the allergen too soon can cause an allergic reaction. Injections are usually given once or twice a week until the maintenance dose is reached. Then injections are usually given every 4 to 6 weeks. The procedure is most effective when maintenance injections are continued throughout the year, even for seasonal allergies.
Alternatively, high doses of the allergen may be placed under the tongue (sublingual) and held there for a few minutes, then swallowed. The dose is gradually increased, as for injections. The sublingual technique is relatively new, and how often the dose should be given has not been established. It ranges from every day to 3 times a week.
Allergen immunotherapy may take 3 to 4 years to complete.
Because immunotherapy injections occasionally cause dangerous allergic reactions, people remain in the doctor's office for at least 30 minutes afterward. If they have mild reactions to immunotherapy (such as sneezing, coughing, flushing, tingling sensations, itching, chest tightness, wheezing, and hives), a drug—usually an antihistamine, such as diphenhydramine or loratadine—may help. For more severe reactions, epinephrine (adrenaline) is injected.
Avoiding the allergen is the best way to treat as well as prevent allergies.
If mild symptoms occur, antihistamines are often all that is needed. If they are ineffective, other drugs, such as mast cell stabilizers and corticosteroids may help. Nonsteroidal anti-inflammatory drugs (NSAIDs) are not useful. Severe symptoms, such as those involving the airways (including anaphylactic reactions), require emergency treatment.
Whenever possible, pregnant women with allergies should avoid allergens in order to control their symptoms. If symptoms are severe, pregnant women should use an antihistamine nasal spray. They should take antihistamines by mouth (oral antihistamines) only if antihistamine nasal sprays do not provide adequate relief. Women who are breastfeeding should also try to avoid antihistamines, but if antihistamines are necessary, antihistamine nasal sprays are preferred to oral antihistamines. If oral antihistamines are essential for controlling symptoms, they should be taken immediately after feeding the baby.
The drugs most commonly used to relieve the symptoms of allergies are antihistamines. Antihistamines block the effects of histamine (which triggers symptoms) rather than stop its production. Taking antihistamines partially relieves the runny nose, watery eyes, and itching and reduces the swelling due to hives or mild angioedema. But antihistamines do not ease breathing when airways are constricted. Some antihistamines are also mast cell stabilizers (see Mast cell stabilizers).
Antihistamines are available as tablets, capsules, or liquid solutions to be taken by mouth or as nasal sprays, eye drops, or lotions or creams. Which is used depends on the type of allergic reaction. Some antihistamines are available without a prescription (over-the-counter), and some require a prescription. Some that used to require a prescription are now available over the counter (OTC).
Products that contain an antihistamine and a decongestant (such as pseudoephedrine) are available OTC. They can be taken by adults and children aged 12 years and older. These products are particularly useful when both an antihistamine and a nasal decongestant are needed. However, some people, such as those who are taking monoamine oxidase inhibitors (a type of antidepressant), cannot take these products. Also, people with high blood pressure should not take a decongestant unless a doctor recommends it and monitors its use.
Diphenhydramine is available OTC as a lotion, cream, gel, or spray that can be applied to the skin to relieve itching, but it should not be used. Its effectiveness is unproved, and it can cause allergic reactions (such as a rash). It can cause extreme drowsiness in children who are also taking an antihistamine by mouth.
Antihistamines have anticholinergic effects, such as drowsiness, dry mouth, blurred vision, constipation, difficulty with urination, confusion, and light-headedness (particularly after a person stands up), as well as drowsiness. Often, prescription antihistamines have fewer of these effects.
Some antihistamines are more likely to cause drowsiness (sedation) than others. Antihistamines that cause drowsiness are widely available OTC. People should not take these antihistamines if they are going to drive, operate heavy equipment, or do other activities that require alertness. These antihistamines should not be given to children under 2 years old because they may have serious or life-threatening side effects. These antihistamines are also a particular problem for older people (see Sidebar 1: Anticholinergic: What Does It Mean?) and for people with glaucoma, benign prostatic hyperplasia, constipation, or dementia because of the drugs' anticholinergic effects. In general, doctors use antihistamines cautiously in people with cardiovascular disease.
Not everyone reacts the same way to antihistamines. For example, Asians seem to be less susceptible to the sedative effects of diphenhydramine than are people of Western European origin. Also, antihistamines cause the opposite (paradoxical) reaction in some people, making them feel nervous, restless, and agitated.
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Mast cell stabilizers:
Mast cell stabilizers inhibit mast cells from releasing histamines and other substances that cause swelling and inflammation. Mast cell stabilizers are taken when antihistamines and other drugs are not effective or have bothersome side effects. These drugs may help control allergic symptoms. These drugs include azelastine, cromolyn, lodoxamide, ketotifen, nedocromil, olopatadine, and pemirolast. Azelastine, ketotifen, olopatadine, and pemirolast are also antihistamines.
Cromolyn is available by prescription for use with an inhaler or nebulizer (which delivers the drug in aerosol form to the lungs), as eye drops, or in forms to be taken by mouth. It is available without a prescription as a nasal spray. Cromolyn usually affects only the areas where it is applied, such as the back of the throat, lungs, eyes, or nose. When taken by mouth, cromolyn can relieve the digestive symptoms of mastocytosis (see Mastocytosis), but it is not absorbed into the bloodstream and thus has no effect on other allergy symptoms.
When antihistamines and mast cell stabilizers cannot control allergy symptoms, a corticosteroid may help. Corticosteroids can be taken as a nasal spray to treat nasal symptoms or through an inhaler, usually to treat asthma.
Doctors prescribe a corticosteroid (such as prednisone) to be taken by mouth only when symptoms are very severe or widespread and all other treatments are ineffective. If taken by mouth at high doses and for a long time (for example, for more than 3 to 4 weeks), corticosteroids can have many, sometimes serious side effects (see Sidebar 3: Corticosteroids: Uses and Side Effects). Therefore, corticosteroids taken by mouth are used for as short a time as possible.
Creams and ointments that contain corticosteroids can help relieve the itching associated with allergic rashes. One corticosteroid, hydrocortisone, is available OTC.
Leukotriene modifiers, such as montelukast, are anti-inflammatory drugs used to treat mild persistent asthma and seasonal allergic rhinitis. They inhibit leukotrienes, which are released by some white blood cells and mast cells when they are exposed to an allergen. Leukotrienes contribute to inflammation and cause airways to constrict.
Omalizumab is a monoclonal antibody (which is a manufactured [synthetic] antibody designed to interact with a specific substance). Omalizumab binds to IgE, an antibody that is produced in large amounts during an allergic reaction, and prevents IgE from binding to mast cells and basophils and triggering an allergic reaction. Omalizumab may be used to treat persistent or severe asthma or allergic rhinitis when other treatments are ineffective. If hives recur frequently and other treatments are ineffective, it may be helpful. When it is used, the dose of a corticosteroid can be reduced. It is given by injection under the skin (subcutaneously).
Severe allergic reactions, such as an anaphylactic reaction, require prompt emergency treatment. People who have severe allergic reactions should always carry a self-injecting syringe of epinephrine. Many of these people also carry antihistamine pills. If a severe reaction occurs, these treatments should be used as quickly as possible. Usually, the combination of epinephrine and an antihistamine stops the reaction, at least temporarily. Nonetheless, people who have had a severe allergic reaction should go to the hospital emergency department, where they can be closely monitored and treatment can be repeated or adjusted as needed.
Last full review/revision May 2014 by Peter J. Delves, PhD |
<urn:uuid:39d8a8da-65ce-4a63-92f1-0efc9dd205f0> | seed | Every year about 70% of neonatal deaths (almost 3 million) happen because effective yet simple interventions do not reach those most in need. Coverage of interventions is low, progress in scaling up is slow, and inequity is high, especially for skilled clinical interventions. Situations vary between and within countries, and there is no single solution to saving lives of newborn babies. To scale up neonatal care, two interlinked processes are required: a systematic, data-driven decision-making process, and a participatory, rights-based policy process. The first step is to assess the situation and create a policy environment conducive to neonatal health. The next step is to achieve optimum care of newborn infants within health system constraints; in the absence of strong clinical services, programmes can start with family and community care and outreach services. Addressing missed opportunities within the limitations of health systems, and integrating care of newborn children into existing programmes—eg, safe motherhood and integrated management of child survival initiatives—reduces deaths at a low marginal cost. Scaling up of clinical care is a challenge but necessary if maximum effect and equity are to be achieved in neonatal health, and maternal deaths are to be reduced. This step involves systematically strengthening supply of, and demand for, services. Such a phased programmatic implementation builds momentum by reaching achievable targets early on, while building stronger health systems over the longer term. Purposeful orientation towards the poor is vital. Monitoring progress and effect is essential to refining strategies. National aims to reduce neonatal deaths should be set, and interventions incorporated into national plans and existing programmes.
Every year, 4 million newborn babies die in the first month of life, 99% in low-income and middle-income countries.1 Babies born in the poorest countries have the highest risk of death, and within these countries the neonatal mortality rate (NMR) among the poorest families is 19—44% higher than among the richest (regional averages based on 48 demographic and health surveys [DHS], 1995—2002). Up to 70% of deaths could be prevented if proven interventions were implemented effectively with high coverage where they are needed most2—a modern-day example of the inverse care law (figure 1).3 Although universal recommendations can be given for evidence-based interventions, the delivery strategy for a particular intervention varies across settings4 and should be adapted to local reality.5 Health care can be delivered through population-oriented outreach services, family-oriented and community-oriented services, and individual-oriented clinical services.
Interventions that have the greatest effect on neonatal deaths are less dependent on technology and commodities than on people with skills. Ideally, every woman should be able to choose to deliver with a skilled attendant present, and if either the mother or her newborn baby have complications, both have the right to access safe professional care. In high-income countries, this ideal exists. In south Asia and sub-Saharan Africa, however, where two-thirds of neonatal (and maternal) deaths happen, only about a third of women deliver in the presence of a skilled attendant. Coverage of postnatal care is lower still, although comparable DHS data are available for only a handful of countries. The average number of mothers giving birth with a skilled attendant in Africa has risen by 0·2% per year for the past decade (http://www.childinfo.org). At this rate, by the year 2015 the average skilled attendant coverage in Africa will still be less than 50%. Rates of caesarean sections are low in the highest mortality countries in Africa.7 Clinical care is even less equitable than antenatal care: within poor countries the richest women have two-times to three-times higher antenatal care coverage than the poorest, but about six-times higher skilled attendance (figure 1). Thus, coverage is low, progress is slow, and inequity is high.
In countries with low coverage of skilled clinical care for maternal and child health, the staff, infrastructure, and support needed to achieve universal coverage are attainable with major investments, but not in the short term.8 Increasing coverage depends on new commitment to a massive increase in the numbers of midwives and doctors as well as innovative approaches to retaining staff, especially in poor rural communities. Even with many new resources, there are no shortcuts: achieving universal coverage of skilled care will take decades. Meanwhile, most neonatal deaths continue to arise in underserved and poor communities—the same communities that will wait the longest for access to skilled care.
In this third paper of the neonatal survival series, we use an adaptation of the four-step management cycle as a guide for scaling up care for newborn babies in different settings (panel 1).9 Two parallel, interdependent processes are needed: a systematic prioritisation and management process, and a rights-based political process, including identification and engagement of key stakeholders. A rights-based approach is necessary to focus attention on tailoring services to the needs of the poor and empowering mothers and communities to adopt good health practices and demand quality care.5, 6, 10 This notion involves a major shift from neonatal care as charity, to a view that holds politicians and providers accountable for the health of babies. We describe the processes with case studies from two countries (Ethiopia and Madagascar) and one large Indian State (Gujarat), and include estimates of the effect and cost of the strategies selected by the governments in these settings. |
<urn:uuid:71c17395-4903-4f70-a924-4a5b94a5d582> | seed | Fleas are a major nuisance. They irritate your cat or dog, they can infest humans and other animals, and they pose health risks. Flea bites transmit tapeworms and cause flea allergy dermatitis, one of the most common allergies in pets. They also cause hair loss and pets may develop secondary irritation or infections from excessive scratching. Because fleas feed on blood, anemia sometimes results from large infestations, especially on young and small animals.
Certain steps help prevent flea infestations before they occur. Not all infestations can be prevented, though. When they strike, deal with them efficiently and effectively. Below are 10 ways to protect your cat or dog against flea bites.
"Fleas are a nuisance because they irritate your cat or dog, they can infest humans and other animals, and they pose health risks."
Flea Control Tips
1. Strap on a flea collar. Flea collars repel and kill fleas. These products must make contact with your pet’s skin. Make sure you can insert two fingers between the collar and your pet’s neck. Snip off any extra length so your cat or dog doesn’t chew on it.
2. Apply a spot-on product in isolated spots, as directed. The medication spreads over your pet’s body via oil on the skin. Many of these products, including Advantage II, PetArmor, and Frontline Plus, kill and repel fleas for several weeks with a single use.
3. Use a flea dip. Flea dips are concentrated chemicals you dilute with water. They are potent and potentially dangerous, so follow the manufacturer’s instructions carefully. These are generally not for use on young cats or dogs.
4. Bathe your pet with a medicated shampoo. Shampoos that kill and repel fleas are a cost-effective option for protecting pets. However, they don’t generally last as long as other products, so reapplication may be necessary every week or two.
5. Apply a flea spray or powder. These products are also cost-effective but shorter lasting than other types of flea treatments. Sprays such as Frontline Spray and powdered products require care during application, as the spray and dust are considerable irritants.
6. Give your pet an oral medication. Oral anti-flea medications like Capstar help keep cats and dogs free of flea infestations with once-monthly use. They also don't involve potentially hazardous applications like topical products.
7. Keep your house clean. Regularly vacuum all carpets in the house. During infestations, vacuum daily, getting in all corners and around the baseboards. Dispose of the vacuum bag outside. Vacuum the car, too, even if your pet hasn’t been in it; you may transport fleas there yourself. Clean your cat or dog’s bedding and toys every day in hot, soapy water.
8. Treat your home. Products that eliminate fleas are available for use on carpets, furniture, and other surfaces. Try Fleabusters or an Adams Flea Fogger. Heed package warnings, as environmental treatments are usually hazardous to children and small animals.
9. Lay flea traps. Place sticky pads or another style of flea trap around the house. These work well for dealing with adult fleas, but they don’t eliminate flea eggs and larvae.
10. Manage your yard. Trim trees, shrubbery, and grass regularly to limit breeding grounds for fleas. If fleas are a big problem in your area, consider calling in an exterminator or investing in outdoor pesticides to use yourself.
The above is provided for information purposes only and should not be used for the diagnosis or treatment of any condition.
This information does not cover all possible variables, conditions, reactions, or risks relating to any topic, medication, or product and should not
be considered complete. Certain products or medications may have risks and you should always consult your local veterinarian concerning the treatment of
your pet. Any trademarks are the property of their respective owners. |
<urn:uuid:b038c6c1-8ee0-4f6e-9be2-efc67b72785c> | seed | Itching is an unpleasant sensation that drives us to scratch reflexively in an effort to remove harmful substances from our body. It’s also how I get most of my physical activity for the day. Not being able to scratch an itch is intensely frustrating and many scientists have long described itch as the milder cousin of pain.
But a team of scientists from Washington University’s Pain Center (I wonder if they have problems with recruitment) have discovered a group of neurons in the spines of mice that are specific to itch but not to pain. Remove them, and mice hardly ever scratch when they’re exposed to itchy chemicals, even though they can still feel pain as well as any normal mouse.
The discovery settles a long-standing debate about whether itch and pain are governed by separate neural systems. It confirms the so-called “labelled line” theory, which says that both sensations depend on different groups of nerve cells.
Two years ago, Yan-Gang Sun and Zhong-Qiu Zhao discovered an itch-specific gene called GRPR that is activated in a small group of neurons in the spinal cords of mice. Without a working copy of this gene, mice became immune to itching but they still responded normally to heat, pressure, inflammation and the noxious flavour of mustard. The duo even managed to stop mice from scratching by injecting them with a chemical that blocks GRPR.
But neurons that activate an itch-specific gene aren’t necessarily restricted to conveying the sensations of itching – they could also be involved in pain. To test that idea, Sun and Zhao injected mice with a nerve poison called bombesin-saporin, which specifically kills neurons that use GRPR. Without these neurons, the mice resisted a wide variety of substances that cause normal mice to scratch furiously, even though their movements were generally unaffected. Just compare the two mice in the video below – both have been injected with an itching agent but the one on the left lacks any working GRPR neurons.
However, even bereft of GRPR neurons, the mice felt pain just as any other mouse would, reacting normally to heat, pressure and noxious chemicals like mustard oil and capsaicin, the active component of chillies. Clearly, these neurons are specific to itch.
A couple of weeks ago, I wrote about propranolol, a drug that can erase the emotion of fearful memories. When volunteers take the drug before recalling a scary memory about a spider, it dulled the emotional sting of future recollections. It’s not, however, a mind-wiping pill in the traditional science-fiction sense, and it can’t erase memories as was so widely reported by the hysterical mainstream media.
The research that’s published today is a different story. Jin-Hee Han from the University of Toronto has indeed found a way to erase a specific fearful memory, but despite the superficial similarities, this is a very different story to the propranolol saga. For a start, Han worked in mice not humans. And unlike the propranolol researchers, who were interested in developing ways of treating people with post-traumatic stress disorder, Han’s goal was to understand how memories are stored in the brain. Erasing them was just a step towards doing that.
Han’s found that a protein called CREB is a molecular beacon that singles out neurons involved in remembering fearful experiences. When a rat experiences something scary, the CREB-neurons in a part of its brain called the amygdala are responsible for storing that memory – for producing what neuroscientists call its “trace”. When Han killed the amygdala’s CREB-neurons, he triggered selective amnesia in the rats, abolishing the specific fears they had been trained to feel. The memory loss was permanent.
This is a major piece of work. Scientists have long believed that memories are represented by specific collections of neurons. But these neurons don’t occur in a neat, tidy clump; they’re often widely spread out, which makes finding the cells that make up any particular memory incredibly challenging. Han has done this by using the CREB protein as a marker. And in doing so, he had highlighted the vital role of this protein in our memories.
I stress again that this isn’t about erasing memories in and of itself. Doing so is just a means to an end – identifying a group of neurons involved in storing a specific memory. For reasons that should become clear in this article, Han’s technique isn’t exactly feasible in humans! Whether this will stop the inevitable run-for-the-hills editorials is perhaps unlikely, but enough speculation: on with the details. |
<urn:uuid:1a445776-fd44-44aa-8bfa-f5cec59613ea> | seed | The public health measures taken in response to swine flu may be seen as alarmist, overly restrictive, or even unjustified, says a US expert in a paper published on bmj.com today.
Peter Doshi, a doctoral student at the Massachusetts Institute of Technology, argues that our plans for pandemics need to take into account more than the worst case scenarios, and calls for a new framework for thinking about epidemic disease.
Over the past four years, pandemic preparations have focused on responding to worst case scenarios. As a result, we responded to the H1N1 outbreak as an unfolding disaster. Some countries erected port of entry quarantines. Others advised against non-essential travel to affected areas and some closed schools and businesses.
Pandemic A/H1N1 is significantly different than the pandemic that was predicted, says Doshi. Pandemic A/H1N1 virus is not a new subtype but the same subtype as seasonal H1N1 that has been circulating since 1977. Furthermore, a substantial portion of the population may have immunity.
Actions in response to the early H1N1 outbreak were taken in an environment of high public attention and low scientific certainty, he argues. The sudden emphasis on laboratory testing for H1N1 in the first weeks of the outbreak helped to amplify the perceived risk.
He also points out that, since the emergence of A/H1N1, the World Health Organisation has revised its definition of pandemic flu.
The wisdom of many of these responses to pandemic A/H1N1 will undoubtedly be debated in the future, he writes. What the early response to the pandemic has shown, however, is that the public health response to, as well as impact and social experience of a pandemic, is heavily influenced by longstanding planning assumptions about the nature of pandemics as disaster scenarios.
If the 2009 influenza pandemic turns severe, early and enhanced surveillance may prove to have bought critical time to prepare a vaccine that could reduce morbidity and mortality, says Doshi. But if this pandemic does not increase in severity, it may signal the need to reassess both the risk assessment and risk management strategies towards emerging infectious diseases.
He suggests that future responses to infectious diseases may benefit from a risk assessment that broadly conceives of four types of threat based on the disease's distribution and clinical severity.
For example, the 1918 pandemic was a type 1 epidemic (severe disease affecting many people), while SARS was a type 2 epidemic (infecting few, mostly severe disease), and the H1N1 pandemic may prove to be type 3 (affecting many, mostly mild).
Public health responses not calibrated to the threat may be perceived as alarmist, eroding the public trust and resulting in the public ignoring important warnings when serious epidemics do occur, he warns.
The success of public health strategies today depends as much on technical expertise as it does on media relations and communications. Strategies that anticipate only type 1 epidemics carry the risk of doing more harm than they prevent when epidemiologically limited or clinically mild epidemics or pandemics occur, he concludes.
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system. |
<urn:uuid:642bb1b6-ebb0-4672-87cd-670f0a661219> | seed | Mesotheliomas are primary benign or malignant tumors arising from the surface lining of the pleura or peritoneum. Eighty percent of reported cases of mesotheliomas affect the pleura, or the thin membrane that covers the lungs and heart. The remaining 20% of the cases affect the peritoneum. More often than not, this disease is a result of chronic exposure to asbestos – a fibrous, heat-resistant compound used in building construction materials, textiles, missile and jet parts, and brake linings. If you have been affected by asbestos exposure, there are numerous legal resources available to assist you. The malignant form of mesothelioma may actually take up to 30 years to develop.
The onset of symptoms of mesothelioma is usually at about 60 years of age. These symptoms include shortness of breath, chest pain, and weight loss. Patients may also present abdominal pain, bowel obstruction, and ascites or swelling of the abdomen due to the accumulation of serous fluid in the peritoneal cavity.
Diagnosing Mesothelioma can be difficult, as the patients may have symptoms, which are similar to other diseases. A physician must be able to review the patient’s medical and occupational histories thoroughly. X-rays and lung function tests are also performed. Radiographic abnormalities may consist of unilateral pleural thickening with varying degrees of pleural effusion. CT scans may help in determining the extent of pleural involvement. Pleural biopsy may also be necessary for histologic diagnosis.
Malignant mesothelioma spreads very quickly. It may eventually extend beyond the thorax into the abdomen, causing involvement of the abdominal organs and lymph nodes. This leads to progressive pain and dyspnea. Unfortunately, the conventional treatment for tumors, consisting of surgery, chemotherapy, radiotherapy, or the combination of these methods, has been tried. However, they came up generally ineffective and unsuccessful. Some surgeons suggested that extrapleural pneumonectomy may be effective if the disease is still in its early stage. Drainage of pleural effusions, radiotherapy, and resectional therapy are also suggested. Nevertheless, all of these treatments rendered to patients with these diseases are only palliative in nature. They only relieve the symptoms, but the disease is not actually eradicated or cured.
The prognosis of this disease is very poor. The survival time from the onset of symptoms is 16 months, if the disease is localized. It is only 5 months, if the disease is already extensive. About 75% of patients with this disease die within 1 year after diagnosis. |
<urn:uuid:65549a52-c3e0-4625-a74f-7e205ca6cadd> | seed | In these conditions the retina slowly degenerates losing its ability to transmit images to the brain. In advanced stages of the conditions, characteristic clumps of pigment appear in the retina. Often the first symptom is night blindness, followed by narrowing of side vision leading to 'tunnel' vision.
Retinitis pigmentosa (RP) is the name given to a group of genetic conditions of the retina, the light-sensitive tissue at the back of the eye. The retina converts light images to nerve signals and sends them to the brain.
The most sensitive part of the retina is small area of the central retina called the macula. The macula contains a few million specialised photoreceptors called cone cells - these work best in bright light levels and are used for reading, writing and to recognise colours. The rest of the retina, called the peripheral retina, is mostly made up of A type of photoreceptor called rod cells. Rod cells enable us to see when light is dim and provide peripheral vision.
Medical text written November 2012 by Professor AT Moore, Professor of Ophthalmology, UCL Institute of Ophthalmology and Moorfields Eye Hospital, London, UK.
What are the symptoms?
What are the causes?
All cases of RP are inherited and a large number of genes have been implicated in causing the condition. In most cases, the peripheral rod cells are affected first with the central cone cells being affected later.
RP can also be associated with other problems such as hearing loss. These rare conditions are referred to as RP syndromes, for example, Usher syndrome.
How is it diagnosed?
A number of tests can be used to diagnose RP:
- retina examination - eye drops are given to dilate the pupils so the retina can be viewed easily
- retinal photographs and specialised retinal imaging - a photograph may be taken of the retina using a special camera.
- visual field test - this checks whether peripheral vision has been affected. The person looks straight ahead at a particular point in the bowl-shaped screen in a darkened room and then dim lights or a moving light are presented in the peripheral field. Each time a spot dots of light is seen the person being tested clicks a button
- colour vision tests - the person will be asked to look at a booklet that shows numbers composed of different coloured dots
- electro-diagnostic tests - the electrical activity of the retina is measured under different lighting conditions and this identifies layers of the retina that are not working properly. This involves having a small wire or thread placed on the eye lids and another on the scalp whilst having watching flashing lights.
How is it treated?
Treatment focuses on managing the symptoms of RP. Wearing sunglasses to protect the retina from ultraviolet light may help preserve vision. For those patients who have poor central vision it can help to see a low-vision specialist, who can help people adapt to vision loss. Regular visits to an eye care specialist, who can detect cataracts or swelling of the retina - both of which can be treated - is essential.
Some studies have suggested that treatment with antioxidants (such as high doses of vitamin A palmitate) may slow the disease but high doses of vitamin A can cause side effects. Several clinical trials are in progress to investigate other dietary treatments for RP, including the omega-3 fatty acid, docosahexaenoic acid (DHA).
Other new treatments such as the use of biological growth factors and gene replacement therapy are being evaluated in clinical trials. Microchip implants that are placed under or on the surface of the retina and stimulate the nerve cells directly are in the early stages of development for treating blindness associated with RP and other serious eye conditions.
Inheritance patterns and prenatal diagnosis
For RP inheritance may be autosomal dominant, autosomal recessive or Inheritance of RP may be autosomal dominant, autosomal recessive or X-linked. Affected families should be referred to a genetics centre for information and support
Prenatal diagnosis is now possible in some forms of RP and other inherited retinal disorders, but only in those cases where the genetic change causing the condition has been identified.
Is there support?
RP Fighting Blindness (British Retinitis Pigmentosa Society)
The Society is a Registered Charity in England and Wales No. 271729, established in 1975. Other conditions covered by the group are macular dystrophy, Best disease, butterfly-shaped dystrophy, Stargardt disease, bull's-eye dystrophy, central areolar choroidal dystrophy, inherited disciform macular degeneration and choroideremia. The eye problems presented by Usher syndrome, Refsum disease and Laurence-Moon-Bardet-Biedl syndrome are also covered. It offers support and contact through a network of branches. It publishes a quarterly newsletter, a monthly e-bulletin and has a wide range of information available. The Society has around 3,000 members.
Group details last confirmed March 2013.
Talk to other families about Retinitis Pigmentosa
We're here for you. Call our freephone helpline
Call us if you need information or advice on any aspect of caring for a disabled child. Monday to Friday, 9.30am to 5pm.
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<urn:uuid:c3511590-93c1-4725-9076-63a93a84d155> | seed | Acute Myocardial Infarction
Cardiovascular disease is the leading cause of death among women in the United States. In fact, according to the 2003 statistical update from the American Heart Association, cardiovascular disease kills over 7 million women annually in the United States, more than the next seven causes of death combined. Of these cardiovascular deaths, the most common cause is acute myocardial infarction (MI). An MI occurs when blood supply to the heart is suddenly interrupted for some period of time. This process may occur because of the development of a thrombus on the surface of a previously existing cholesterol plaque in the coronary arteries. If this blockage is complete and persists for some time—often greater than 30-60 min— the result may be death to the myocardium supplied by this vessel, a so-called transmural infarction. In other situations, the blockage may not completely obstruct all myocardial blood flow, yet it persists and leads to damage. The resulting infarction is termed nontransmural, indicating that the damage has not been as extensive. On occasion, MIs may also be caused by spasm of the coronary artery or very transient obstruction that cannot be identified on later angiographic evaluation.
The pathophysiology that leads to an MI is the same in women and men; however, there are important gender differences that are apparent on presentation with MI. Women are less likely than men to present with an acute transmural infarction (also called an “ST-elevation MI” because of the typical EKG pattern). Instead, women more often experience nontransmural (“non-ST-elevation”) infarctions or acute coronary symptoms not resulting in an MI. This more subtle presentation may be one reason why physicians and laypersons tended to consider coronary heart disease less as a disease of women than of men. In fact, multiple studies have shown that, compared with men, women present later to the hospital with an MI, are less likely to receive important thrombolytic drugs when appropriate, and are less likely to be referred for coronary angiography. Furthermore, because MI is often not correctly diagnosed, women are less likely to receive appropriate medications and cardiac rehabilitation.
Recent findings have effectively destroyed the myth that MI is a less important disease in women than in men. On the one hand, women have important differences from men who present with MI—on average, the women are 10-20 years older, with more elevated cholesterol levels and possibly more hypertension, but a lower prevalence of cigarette smoking. Women also are more likely to have diabetes, which is a major risk factor for poor outcome with MI and, when present, negates any gender benefit for women. In addition, women who sustain an MI are also as much as 50% more likely to die in the short term as are men. Finally, perhaps because of their older age and greater extent of other illness, women are more likely to suffer so-called mechanical complications of MI, such as cardiac rupture.
In addition to the different characteristics of women and men with MI, there are important differences in the symptoms that each gender tends to report upon presentation. The classic symptoms, such as the sudden onset of pressure centered in the chest, radiating down one or both arms, and associated with a “cold sweat” (or diaphoresis), should be considered more as the typical middle-aged male symptoms associated with MI. While both genders certainly experience a full range of symptoms, women are much less likely to have these so-called “classic” symptoms and are more likely to have a wider range of complaints, including shortness of breath (dyspnea), nausea or vomiting, and pains in the jaw, back, or even abdomen, with or without chest pain. Women are also more likely to sustain an MI without any characteristic symptoms—the socalled “silent MI.” It is now recognized that any individual—either physician or layperson—who relies on more stereotypical chest pain symptoms for diagnosis will fail to appreciate early symptoms of an MI more often in women than in men.
Good news is that the therapies for MI have, almost uniformly, provided strong benefit to both genders. Unfortunately, there is mounting evidence that women do not receive these therapies as often as men. For patients with an ST-elevation MI, the accepted beneficial therapies include thrombolytic therapy and “primary angioplasty,” which involve emergent coronary angiography to identify the occlusion and then angioplasty to open the artery. Both of these therapies work in women and men, and in the multitude of medical studies to evaluate these treatments, it appears that the benefit for women is similar to the benefit extended to men. However, because women with MI tend to be older, with greater comorbidity, and because they are on average smaller in body size than men, they may have more problems with bleeding with all therapies and may sometimes not be eligible for thrombolytic therapy. Furthermore, among older patients, there is a concern that women may have more complications with thrombolytics, and some investigators have proposed that primary angioplasty is a better treatment for women. However, it is also true that women may arrive at the hospital too late for thrombolysis, emphasizing that women, their families, and their physicians need to recognize possible signs of MI and present to emergency departments promptly so that appropriate therapy may be pursued.
Just as important as rapid treatment for STelevation MI, is appropriate therapy for non-ST-elevation MI, the more common presentation for women. While thrombolytic therapy is not an effective treatment for this condition, a wide range of medical therapies significantly reduce the risk associated with this type of infarction. Relative to management of this condition, debates within the cardiology community have recently focused on the routine use of certain medications, most notably the glycoprotein IIb/IIIa inhibitors, and the routine use of an “early aggressive strategy,” which involves early catheterization and intervention as needed for patients with non-ST-elevation MI. While there has been some evidence that women do not receive as great a benefit with IIb/IIIa inhibitors as do men, a recent study that used these agents in the evaluation of early catheterization demonstrated that the benefit of an “aggressive strategy” was just as strong in women as in men, but of particular benefit in high-risk women.
Medications that should be considered for all patients with MI provide benefits to both genders, in the setting of ST-elevation or non-ST-elevation infarction. The most important of these drugs remains aspirin, which in the early studies of ST-elevation MI provided benefit equal and in addition to that of thrombolytic therapy. Other drugs that must be considered include betablockers (which may provide even stronger benefits to women than to men), ACE inhibitors, and statin medications. The statins, which lower blood cholesterol levels, have demonstrated on average a 20% reduction in mortality in all patients with coronary disease, and there is no evidence of preferential effect by gender. One note specific to women is that the majority of evidence now indicates that hormone replacement therapy does not provide any special level of protection before or after MI.
After recognition of an appropriate therapy for MI, other procedures and treatments may be appropriate for women. Some of these, such as nuclear cardiac scans or echocardiograms, can give a better indication of individual levels of risk and guide intensity of treatment. Other treatments, such as cardiac rehabilitation, including exercise training and secondary prevention, are powerful tools that, again, physicians have been less likely to offer to women than to men.
Scientific knowledge has increased the understanding of the burden of cardiovascular disease in women. With a better appreciation of the clinical characteristics and symptoms that mark acute MI in women, we are now much more able to provide therapies of proven benefit to all patients.
SEE ALSO: Cardiovascular disease, Chest pain, Cholesterol, Diabetes, Hormone replacement therapy, Smoking
- myocardial infarction in women
- acute MI in women rghus
- myocardial infracture on women
- Myocardial Infarction Women
- myocardial infarction
- EKG Acute MI female
- acute myocardial infarction in women
- Acute MI Symptoms in Women
- acute MI symptoms for older women
- specific symptoms of womens cardiac infarction |
<urn:uuid:110bab28-c637-4e0e-9ef2-a8f085e71ab1> | seed | This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: HMP-PP biosynthesis
|Superclasses:||Biosynthesis → Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis → Vitamins Biosynthesis → Thiamin Biosynthesis|
Thiamin diphosphate, also known as vitamin B1, is known to play a fundamental role in energy metabolism. It is an essential cofactor for a variety of enzymes such as transketolase, pyruvate dehydrogenase, pyruvate decarboxylase, and α-ketoglutarate dehydrogenase [Lawhorn04]. Its discovery followed from the original early research on the anti-beriberi factor found in rice bran. Beriberi, a neurological disease, was particularly prevalent in Asia, where the refining of rice resulted in the removal of the thiamin-containing husk [Begley96]. Thiamin is synthesized de novo by microorganisms, plants and some lower eukaryotes (e.g. Plasmodium
Thiamin biosynthesis is composed of the separate formation of the pyrimidine and thiazole moieties, which are subsequently coupled to form thiamin phosphate (see for example thiamin diphosphate biosynthesis II (Bacillus)).
About This Pathway
This pathway describes the synthesis of the pyrimidine moiety of thiamin. Starting with 5-amino-1-(5-phospho-β-D-ribosyl)imidazole, an intermdiate in purine biosynthesis, two enzymatic steps, catalyzed by ThiC and ThiD, produce 4-amino-2-methyl-5-diphosphomethylpyrimidine. The first reaction is one of the most complicated rearrangement reactions known. The ThiC enzyme belongs to the radical SAM family, all members of which utilize S-adenosyl-L-methionine (SAM) to generate an 5'-deoxyadenosyl radical that in turn serves as an oxidant for a wide variety of enzymatic reactions [Chatterjee08]. The first stage of catalysis is the reduction of SAM to produce L-methionine and a 5-deoxyadenosyl radical, which is generated at the active site. The radical reacts directly with the substrate to catalyze a complex rearrangement reaction that includes two iterative hydrogen atom abstractions (which necessitates the regeneration of the radical following the first abstraction). C1' and C3' of the substrate, which are not inorporated into the product, are converted to formate and carbon monoxide, respectively [Chatterjee10].
The second enzyme, ThiD, is a simple kinase. It is a bifunctional enzyme, and can also phosphorylate 4-amino-2-methyl-5-pyrimidinemethanol, as a part of a thiamin salvage pathway (see thiamin salvage II) [Park04a].
Variants: 4-amino-2-methyl-5-phosphomethylpyrimidine biosynthesis (yeast) , thiamin diphosphate biosynthesis I (E. coli) , thiamin diphosphate biosynthesis II (Bacillus) , thiamin diphosphate biosynthesis III (Staphylococcus) , thiamin diphosphate biosynthesis IV (eukaryotes) , thiamin formation from pyrithiamine and oxythiamine (yeast) , thiamin triphosphate metabolism , thiazole biosynthesis I (E. coli) , thiazole biosynthesis II (Bacillus) , thiazole biosynthesis III (eukaryotes)
Unification Links: EcoCyc:PWY-6890
Chatterjee08: Chatterjee A, Li Y, Zhang Y, Grove TL, Lee M, Krebs C, Booker SJ, Begley TP, Ealick SE (2008). "Reconstitution of ThiC in thiamine pyrimidine biosynthesis expands the radical SAM superfamily." Nat Chem Biol 4(12);758-65. PMID: 18953358
Chatterjee10: Chatterjee A, Hazra AB, Abdelwahed S, Hilmey DG, Begley TP (2010). "A "Radical Dance" in Thiamin Biosynthesis: Mechanistic Analysis of the Bacterial Hydroxymethylpyrimidine Phosphate Synthase." Angew Chem Int Ed Engl 49(46);8653-6. PMID: 20886485
Park04a: Park JH, Burns K, Kinsland C, Begley TP (2004). "Characterization of two kinases involved in thiamine pyrophosphate and pyridoxal phosphate biosynthesis in Bacillus subtilis: 4-amino-5-hydroxymethyl-2methylpyrimidine kinase and pyridoxal kinase." J Bacteriol 186(5);1571-3. PMID: 14973012
Ajjawi07: Ajjawi I, Tsegaye Y, Shintani D (2007). "Determination of the genetic, molecular, and biochemical basis of the Arabidopsis thaliana thiamin auxotroph th1." Arch Biochem Biophys 459(1);107-14. PMID: 17174261
DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114
Dougherty06: Dougherty MJ, Downs DM (2006). "A connection between iron-sulfur cluster metabolism and the biosynthesis of 4-amino-5-hydroxymethyl-2-methylpyrimidine pyrophosphate in Salmonella enterica." Microbiology 152(Pt 8);2345-53. PMID: 16849799
Haas05: Haas AL, Laun NP, Begley TP (2005). "Thi20, a remarkable enzyme from Saccharomyces cerevisiae with dual thiamin biosynthetic and degradation activities." Bioorg Chem 33(4);338-44. PMID: 15967475
Kim98d: Kim YS, Nosaka K, Downs DM, Kwak JM, Park D, Chung IK, Nam HG (1998). "A Brassica cDNA clone encoding a bifunctional hydroxymethylpyrimidine kinase/thiamin-phosphate pyrophosphorylase involved in thiamin biosynthesis." Plant Mol Biol 37(6);955-66. PMID: 9700068
Komeda88: Komeda Y, Tanaka M, Nishimune T (1988). "A th-1 Mutant of Arabidopsis thaliana Is Defective for a Thiamin-Phosphate-Synthesizing Enzyme: Thiamin Phosphate Pyrophosphorylase." Plant Physiol 88(2);248-250. PMID: 16666289
Llorente99: Llorente B, Fairhead C, Dujon B (1999). "Genetic redundancy and gene fusion in the genome of the Baker's yeast Saccharomyces cerevisiae: functional characterization of a three-member gene family involved in the thiamine biosynthetic pathway." Mol Microbiol 32(6);1140-52. PMID: 10383756
LopezCampistrou05: Lopez-Campistrous A, Semchuk P, Burke L, Palmer-Stone T, Brokx SJ, Broderick G, Bottorff D, Bolch S, Weiner JH, Ellison MJ (2005). "Localization, annotation, and comparison of the Escherichia coli K-12 proteome under two states of growth." Mol Cell Proteomics 4(8);1205-9. PMID: 15911532
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<urn:uuid:df15f573-b924-40f1-891f-bdba6513984f> | seed | Nanoengineers at the University of California, San Diego have developed a 3D-printed device inspired by the liver to remove dangerous toxins from the blood. The device, which is designed to be used outside the body -- much like dialysis - uses nanoparticles to trap pore-forming toxins that can damage cellular membranes and are a key factor in illnesses that result from animal bites and stings, and bacterial infections. Their findings were published May 8 in the journal Nature Communications.
Nanoparticles have already been shown to be effective at neutralizing pore-forming toxins in the blood, but if those nanoparticles cannot be effectively digested, they can accumulate in the liver creating a risk of secondary poisoning, especially among patients who are already at risk of liver failure. To solve this problem, a research team led by nanoengineering professor Shaochen Chen created a 3D-printed hydrogel matrix to house nanoparticles, forming a device that mimics the function of the liver by sensing, attracting and capturing toxins routed from the blood. The device, which is in the proof-of-concept stage, mimics the structure of the liver but has a larger surface area designed to efficiently attract and trap toxins within the device. In an in vitro study, the device completely neutralized pore-forming toxins.
"One unique feature of this device is that it turns red when the toxins are captured," said the co-first author, Xin Qu, who is a postdoctoral researcher working in Chen's laboratory. "The concept of using 3D printing to encapsulate functional nanoparticles in a biocompatible hydrogel is novel," said Chen. "This will inspire many new designs for detoxification techniques since 3D printing allows user-specific or site-specific manufacturing of highly functional products," Chen said.
Chen's lab has already demonstrated the ability to print complex 3D microstructures, such as blood vessels, in mere seconds out of soft biocompatible hydrogels that contain living cells.
Chen's biofabrication technology, called dynamic optical projection stereolithography (DOPsL), can produce the micro- and nanoscale resolution required to print tissues that mimic nature's fine-grained details, including blood vessels, which are essential for distributing nutrients and oxygen throughout the body. The biofabrication technique uses a computer projection system and precisely controlled micromirrors to shine light on a selected area of a solution containing photo-sensitive biopolymers and cells. This photo-induced solidification process forms one layer of solid structure at a time, but in a continuous fashion. The technology is part of a new biofabrication technology that Chen is developing under a four-year,$1.5 million grant from the National Institutes of Health (R01EB012597). The project is also supported in part by a grant (CMMI-1120795) from the National Science Foundation. |
<urn:uuid:bacf23dd-0b50-4913-8f90-93bb6ef1e21b> | seed | Echinocandins are antifungal drugs that inhibit the synthesis of glucan in the cell wall, via noncompetitive inhibition of the enzyme 1,3-β glucan synthase and are thus called[by whom?] penicillin of antifungals (a property shared with papulacandins) as penicillin has a similar mechanism against bacteria but not fungi. Beta glucans are carbohydrate polymers that are cross-linked with other fungal cell wall components (The bacterial equivalent is peptidoglycan).
They are fungicidal against some yeasts (most species of Candida, but not against Cryptococcus, Trichosporon and Rhodotorula), fungistatic against some molds (Aspergillus, but not Fusarium and Rhizopus), and modestly or minimally active active against dimorphic fungi (Blastomyces and Histoplasma). These have some activity against the spores of the fungus Pneumocystis carinii.
The present-day clinically used echinocandins are semisynthetic pneumocandins, which are chemically lipopeptide in nature, consisting of large cyclic (hexa)peptides linked to a long-chain fatty acid. Discovery of echinocandins stemmed from studies on papulacandins isolated from a strain of Papularia sphaerosperma (Pers.), which were liposaccharide - i.e., fatty acid derivatives of a disaccharide that also blocked the same target, 1,3-β glucan synthase - and had action only on Candida spp. (narrow spectrum). Screening of natural products of fungal fermentation in the 1970s led to the discovery of echinocandins, a new group of antifungals with broad-range activity against Candida spp. One of the first echinocandins of the pneumocandin type, discovered in 1974, echinocandin B, could not be used clinically due to risk of high degree of hemolysis. Screening semisynthetic analogs of the echinocandins gave rise to cilofungin, the first echinofungin analog to enter clinical trials, in 1980, which, it is presumed, was later withdrawn for a toxicity due to the solvent system needed for systemic administration. The semisynthetic pneumocandin analogs of echinocandins were later found to have the same kind of antifungal activity, but low toxicity. The first approved of these newer echinocandins was caspofungin, and later micafungin and anidulafungin were also approved. All these preparations so far have low oral bioavailability, so must be given intravenously only. Echinocandins have now become one of the first line treatments for Candida before the species are identified, and even as antifungal prophylaxis in hematopoietic stem cell transplant patients.
Advantages of echinocandins:
- broad range (especially against all Candida), thus can be given empirically in febrile neutropenia and stem cell transplant
- can be used in case of azole-resistant Candida or use as a second line agent for refractory aspergillosis
- long half-life (polyphasic elimination: alpha phase 1–2 hours + beta phase 9–11 hours + gamma phase 40–50 hours)
- low toxicity: only histamine release (3%), fever (2.9%), nausea and vomiting (2.9%), and phlebitis at the injection site (2.9%), very rarely allergy and anaphylaxis
- not an inhibitor, inducer, or substrate of the cytochrome P450 system, or P-glycoprotein, thus minimal drug interactions
- lack of interference from renal failure and hemodialysis
- no dose adjustment is necessary based on age, gender, race
- better (or no less effective) than amphotericin B and fluconazole against yeast infections
Disadvantages of echinocandins:
- embryotoxic (category C) thus cannot be used in pregnancy
- needs dose adjustment in liver disease
- poor ocular penetration in fungal endophthalmitis
Caspofungin has some interference with ciclosporin metabolism, and micafungin has some interference with sirolimus (rapamycin), but anidulafungin needs no dose adjustments when given with ciclosporin, tacrolimus, or voriconazole.
List of echinocandins:
- pneumocandins (cyclic hexapeptides linked to a long-chain fatty acid):
- Morris MI, Villmann M (September 2006). "Echinocandins in the management of invasive fungal infections, part 1". Am J Health Syst Pharm 63 (18): 1693–703. doi:10.2146/ajhp050464.p1. PMID 16960253.
- Morris MI, Villmann M (October 2006). "Echinocandins in the management of invasive fungal infections, Part 2". Am J Health Syst Pharm 63 (19): 1813–20. doi:10.2146/ajhp050464.p2. PMID 16990627.
- Wagner C, Graninger W, Presterl E, Joukhadar C (2006). "The echinocandins: comparison of their pharmacokinetics, pharmacodynamics and clinical applications". Pharmacology 78 (4): 161–77. doi:10.1159/000096348. PMID 17047411.
- "Pharmacotherapy Update - New Antifungal Agents: Additions to the Existing Armamentarium (Part 1)".
- Gauthier GM, Nork TM, Prince R, Andes D (August 2005). "Subtherapeutic ocular penetration of caspofungin and associated treatment failure in Candida albicans endophthalmitis". Clin. Infect. Dis. 41 (3): e27–8. doi:10.1086/431761. PMID 16007519.
- Harroison's Principle of Internal Medicine |
<urn:uuid:b7ac7cba-8d87-47ef-9ea8-a6f0c2c5e51a> | seed | Golden Nano-DumbbellsApril 5th, 2007 in Nanotechnology / Nanomaterials
Nanotechnology appears to be an unstoppable trend and it requires defined nanoscale building blocks and patterns. “A typical difficulty with the synthesis of nanostructures is the modification of nanoscale objects at specific positions” says Alexander Bittner, whose work with a team from the Max Planck Institute for Solid-State Research in Stuttgart and Christina Wege's research team at the University of Stuttgart has led to an important breakthrough.
As reported in the journal Angewandte Chemie, the scientists were successful in selectively modifying the ends of nanoscale rods by selectively binding gold nanoparticles to the ends of tubular viruses. By using an electroless gold-plating technique, the gold ends can be enlarged to form dumbbell-shaped structures.
Their highly symmetrical structures and uniform size distribution make biological molecules like DNA and whole “almost organisms” like viruses ideal “molds” for the exact positioning of nano-objects and the synthesis of structured nanomaterials. In their experiments, the Stuttgart scientists chose to use the tobacco mosaic virus, a harmless plant virus shaped like a 300-nm long tube. The researchers mixed a suspension of these viruses with a liquid that contained very finely dispersed gold particles, called a gold sol. The gold particles in the sol carry citrate molecules on their surface.
Examination with an electron microscope revealed something interesting: Individual gold particles bind to the viruses, but only at the ends. The reason for this lies in the RNA, the genetic material of the virus. Wege stated that “in the tobacco mosaic virus, the RNA is usually embedded deep in the protein shell, but not at the ends of the virus tubes”. In fact, it has been demonstrated that gold particles from the gold sol bind to free RNA in a similar way. Bittner and his colleagues postulate that the aromatic bases of the RNA are used to bind and displace citrate molecules from the gold surface.
The researchers then place the virus–gold structures on a support and dip them into a gold bath (an electroless gold-plating technique). Additional gold is thus deposited onto the gold nanoparticles that are already bound to the ends of the rods, resulting in dumbbell-shaped structures. Bittner and Wege envision a large number of different applications for these nanodumbbells; for instance, they could be used as junctions for nanoscale electrical wiring.
Citation: Alexander M. Bittner, Self-Assembly of Metal–Virus Nanodumbbells, Angewandte Chemie International Edition 2007, 46, No. 17, 3149–3151, doi: 10.1002/anie.200604558
Source: Angewandte Chemie
"Golden Nano-Dumbbells." April 5th, 2007. http://phys.org/news94979176.html |
<urn:uuid:4493aa0c-59e6-4e8e-b4f3-67a88e6d6564> | seed | |Home > Facts > Children's Diets|
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Central Europeans and Russians, Diets of
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Because children grow at different rates and at different times, it becomes harder to distinguish if a child is overweight compared to establishing overweight in adults. To determine if a child is within an un-healthy weight range, a doctor will use certain criteria to measure a child’s height and weight. The body mass index (BMI), expressed as body weight in kilograms divided by the square of height in meters (kg/m2), is a weight-for-height index. The BMI is the standard obesity assessment in adults, and its use within the pediatric population has limited research to support its effectiveness is still considered the standard measure of overweight in children. The International
(Illustrated by GGS Information Services/Thomson Gale.)
Task Force on Obesity approved that BMI provides a reasonable index of adiposity and provides a reliable measure across pediatric age groups.
A children’s BMI score is the criteria used by medical professionals to determine an un-healthy weight. Any child who’s BMI falls between the 85th and 95th percentile for age and sex should be evaluated for secondary complications of obesity, including hypertension and dyslipidemias. An extensive change in BMI would also call for evaluation and possible treatment of the child. Although the degree of change that indicates risk has not been defined, an annual increase of three to four BMI units is thought to reflect concern due to possible increases in a child’s body fat.
In the United States and elsewhere in developed countries, the prevalence of childhood obesity has drastically risen in the past several decades.
Since the 1960s, the prevalence of obesity in children has been assessed by several nationally representative surveys. These include the National Health Examination Survey Cycles I to III and the National Health and Nutrition Examination Surveys I to III. Based on these surveys, the obesity among children is
estimated to be 25–30%. Furthermore, they estimated the proliferation of obesity has increased by 54% in children six to 11 years of age and by 39% in adolescents 12 to 17 years of age. Morbid obesity jumped 98% and 64% within these groups, respectively. Hispanic, Native American and black children tend to have higher rates in relation to other populations.
Because of these statistics, weight loss diets for children have surfaced. Although weight loss in children is a hot debate in the medical field, there are times when a child’s weight should be evaluated and possibly treated by medical professionals who specialize in weight loss for children.
Childhood obesity can cause complications in many organ systems. These obesity-related medical conditions include cardiovascular disease; type 2 diabetes mellitus, and degenerative joint disease.
Orthopedic complications include slipped capital femoral epiphysis that occurs during the adolescent growth spurt and is most frequent in obese children. The slippage causes a limp and/or hip, thigh and knee pain in children and can result in considerable disability.
Blount’s disease (tibia vara) is a growth disorder of the tibia (shin bone) that causes the lower leg to angle inward, resembling a bowleg. The cause is unknown but is associated with obesity. It is thought to be related to weight-related effects on the growth plate. The inner part of the tibia, just below the knee, fails to develop normally, causing angulation of the bone.
Overweight children with hypertension may experience blurred margins of the optic disks that may indicate pseudotumor cerebri, this creates severe headaches and may lead to loss of visual fields or visual acuity.
Research shows that 25 out of 100 overweight, inactive children tested positive for sleep-disordered breathing. The long-term consequences of sleep-disordered breathing on children are unknown. As in adults, obstructive sleep apnea can cause a lot of complications, including poor growth, headaches, high blood pressure and other heart and lung problems and they are also potentially fatal disorders.
Abdominal pain or tenderness may reflect gall bladder disease, for which obesity is a risk factor in adults, although the risk in obese children may be much lower. Children who are overweight have a higher risk for developing gallbladder disease and gallstones because they may produce more cholesterol, a risk factor for gallstones. Or due to being overweight, they may have an enlarged gallbladder, which may not work properly.
Endocrinologic disorders related to obesity include noninsulin-dependent diabetes mellitus (NIDDM), an increasingly common condition in children that once used to be extremely rare. The link between obesity and insulin resistance is well documented and which is a major contributor to cardiovascular disease.
Hypertension (high blood pressure), and dyslipi-demias (high blood lipids), conditions that add to the long-term cardiovascular risks conferred by obesity are common in obese children.
Childhood obesity also threatens the psychosocial development of children. In a society that places such a high premium on thinness, obese children often become targets of early and systematic discrimination that can seriously hinder healthy development of body image and self-esteem, thus leading to depression and possibly suicide.
In all of these examples, it is recommended that the primary clinician should consult a pediatric obesity specialist about an appropriate weight-loss or weight maintenance program.
Only a small percentage of childhood obesity is associated with a hormonal or genetic defect, with the remainder being environmental in nature due to lifestyle and dietary factors. Although rarely encountered, hypo-thyroidism is the most common endogenous abnormality in obese children and seldom causes massive weight gain.
Of the diagnosed cases of childhood obesity, roughly 90% of the cases are considered environmental in nature and about 10% are endogenous in nature.
The Division of Pediatric Gastroenterology and Nutrition, New England Medical Center, Boston, Massachusetts as well as many child organizations agree that the primary goal of a weight loss program for children to manage uncomplicated obesity is healthy eating and activity, not achievement of ideal body weight. Any program designed for the overweight or obese child should emphasize behavior modification skills necessary to change behavior and to maintain those changes.
For children with a secondary complication of obesity, improvement or resolution of the complication is an important medical goal. Abnormal blood pressure or lipid profile may improve with weight control, and will reinforce to the child and their parents/caregivers that weight control leads to improvement in health even if the child does not approach ideal body weight.
In review of much research, expert advice is that most children who are overweight should not be placed on a weight loss diet solely intended to lose weight. Instead they should be encouraged to maintain current weight, and gradually “grow into” their weight, as they get taller. Furthermore, children should never be put on a weight-loss diet without medical advice as this can affect their growth as well as mental and physical health. In view of current research, prolonged weight maintenance, done through a gradual growth in height results in a decline in BMI and is a satisfactory goal for many overweight and obese children. The experience of clinical trials suggests that a child can achieve this goal through modest changes in diet and activity level.
For most children, prolonged weight maintenance is an appropriate goal in the absence of any secondary complication of obesity, such as mild hypertension or dyslipidemia. However, children with secondary complications of obesity may benefit from weight loss if their BMI is at the 95th percentile or higher. For children older than 7 years, prolonged weight maintenance is an appropriate goal if their BMI is between the 85th and 95th percentile and if they have no secondary complications of obesity. However, weight loss for children in this age group with a BMI between the 85th and 95th percentile who have a nonacute secondary complication of obesity and for children in this age group with a BMI at the 95th percentile or above is recommended by some organizations.
When weight loss goals are set by a medical professional, they should be obtainable and should allow for normal growth. Goals should initially be small; one-quarter of a pound to two pounds per week. An appropriate weight goal for all obese children is a BMI below the 85th percentile, although such a goal should be secondary to the primary goal of weight maintenance via healthy eating and increases in activity.
Components of a Successful Weight Loss Plan Many studies have demonstrated a familial correlation of risk factors for obesity. For this reason, it is important to involve the entire family when treating obesity in children. It has been demonstrated that the long-term effectiveness of a weight control program is significantly improved when the intervention is directed at the parents as well as the child. Below describes beneficial components that should be incorporated into a weight maintenance or weight loss effort for overweight or obese children.
Adverse effects of childhood weight loss may include gall bladder disease, which can occur in adolescents who lose weight rapidly. Another concern is inadequate nutrient intake of essential or non-essential nutrients. Linear growth may slow during weight loss. However, impact on adult stature appears to be minimal. Loss of lean body mass may occur during weight loss. The effects of rapid weight loss (more than 1 pound per month) in children younger than 7 years are unknown and are thus not recommended.
There is a clear association between obesity and low self-esteem in adolescents. This relation brings other concerns that include the psychological or emotional harm a weight loss program may infer on a child. Eating disorders may arise, although a supportive, nonjudgmental approach to therapy and attention to the child’s emotional state minimize this risk. A child or parent’s preoccupation with the child’s weight may damage the child’s self-esteem. If weight, diet, and activity become areas of conflict, the relationship between the parent and child may deteriorate.
Once the need for obesity treatment has been identified, a medical professional may suggest one or more options. Consultation with a dietitian / nutritionist that specializes in children’s needs is often a valuable part of obesity treatment.
Behavior therapy involves changes in diet and physical activity habits that promote weight maintenance or loss. Some behavioral therapy strategies for children and adolescents should include parent and family involvement. And should be supervised by a medical professional.
DRUG TREATMENT. The U.S. Food and Drug Administration has not yet approved the use of any drugs to treat obesity in children. However, clinical trials are under way.
SURGERY. Surgical procedures such as gastric bypass have been performed successfully on adolescents. However surgery for adolescents is usually considered only when severe medical conditions are present that can improve with the surgery and other treatment options have failed.
BMI age-for-growth charts for the United States are available at http://www.cdc.gov/nccdphp/dnpa/bmi/bmi-for-age.htm.
Encourages kids to get physically active. http://www.verbnow.com/.
Healthy eating and physical activity tips for kids and parents. http://www.kidnetic.com/.
Information about nutrition and fitness for kids. http://www.kidshealth.org/.
MyPyramid Plan. MyPyramid replaces the Food Guide Pyramid. Available from the U.S. Department of Agriculture (USDA) at www.mypyramid.gov.
The Shapedown Pediatric Obesity Program. http://www.shapedown.com.
The Weight-control Information Network (WIN) www.niddk.nih.gov/health/nutrit/pubs/parentips/tipsforparents.htm.
Megan C.M. Porter, RD, LD |
<urn:uuid:eb3d8534-3bb7-42a6-b165-6ed5f8442004> | seed | Scientists have identified factors that increase the risk of Alzheimer’s. The most important risk factors—age, family history and heredity—can’t be changed, but emerging evidence suggests there may be other factors we can influence.
The greatest known risk factor for Alzheimer’s is advancing age. Most individuals with the disease are age 65 or older. The likelihood of developing Alzheimer’s doubles about every five years after age 65. After age 85, the risk reaches nearly 50 percent. One of the greatest mysteries of Alzheimer’s disease is why risk rises so dramatically as we grow older.
Another strong risk factor is family history. Those who have a parent, brother, sister or child with Alzheimer’s are more likely to develop the disease. The risk increases if more than one family member has the illness. When diseases tend to run in families, either heredity (genetics) or environmental factors, or both, may play a role.
Scientists know genes are involved in Alzheimer’s. There are two types of genes that can play a role in affecting whether a person develops a disease—risk genes and deterministic genes. Alzheimer’s genes have been found in both categories.
- Risk genes increase the likelihood of developing a disease, but do not guarantee it will happen. Scientists have so far identified several risk genes implicated in Alzheimer’s disease. The risk gene with the strongest influence is called apolipoprotein E-e4 (APOE-e4). Scientists estimate that APOE-e4 may be a factor in 20 to 25 percent of Alzheimer’s cases.APOE-e4 is one of three common forms of the APOE gene; the others are APOE-e2 and APOE-e3.
- Everyone inherits a copy of some form of APOE from each parent. Those who inherit APOE-e4 from one parent have an increased risk of Alzheimer’s. Those who inherit APOE-e4 from both parents have an even higher risk, but not a certainty. Scientists are not yet certain how APOE-e4 increases risk. In addition to raising risk, APOE-e4 may tend to make Alzheimer’s symptoms appear at a younger age than usual.
- When Alzheimer’s disease is caused by these deterministic variations, it is called “autosomal dominant Alzheimer’s disease (ADAD)” or “familial Alzheimer’s disease,” and many family members in multiple generations are affected. Symptoms nearly always develop before age 60, and may appear as early as a person’s 30s or 40s. Deterministic Alzheimer’s variations have been found in only a few hundred extended families worldwide. True familial Alzheimer’s accounts for less than 5 percent of cases.
- Deterministic genes directly cause a disease, guaranteeing that anyone who inherits them will develop the disorder. Scientists have discovered variations that directly cause Alzheimer’s disease in the genes coding three proteins: amyloid precursor protein (APP), presenilin-1 (PS-1) and presenilin-2 (PS-2).
Genetic tests are available for both APOE-e4 and the rare genes that directly cause Alzheimer’s. However, health professionals do not currently recommend routine genetic testing for Alzheimer’s disease. Testing for APOE-e4 is sometimes included as a part of research studies. Learn more: Genetic Testing Topic Sheet
A Closer Look: Genes Linked to Alzheimer’s
The 23 human chromosome pairs contain all of the 30,000 genes that code the biological blueprint for a human being. This interactive illustration highlights the chromosomes containing each of the three genes that cause familial Alzheimer’s and the gene with the greatest impact on Alzheimer’s risk.
23 chromosome pairs
- Amyloid precursor protein (APP), discovered in 1987, is the first gene with mutations found to cause an inherited form of Alzheimer’s.
- Presenilin-1 (PS-1), identified in 1992, is the second gene with mutations found to cause early-onset of Alzheimer’s. Variations in this gene are the most common cause of early-onset Alzheimer’s.
- Presenilin-2 (PS-2), 1993, is the third gene with mutations found to cause early-onset Alzheimer’s.
- Apolipoprotein E-e4 (APOE4), 1993, is the first gene variation found to increase risk of Alzheimer’s and remains the risk gene with the greatest known impact. Having this mutation, however, does not mean that a person will develop the disease.
What You Can Do Now: Factors You May Be Able to Influence
Most experts believe that the majority of Alzheimer’s disease occurs as a result of complex interactions among genes and other risk factors. Age, family history and heredity are all risk factors we can’t change. Now, research is beginning to reveal clues about other risk factors we may be able to influence through general lifestyle and wellness choices and effective management of other health conditions.
Head trauma: There may be a strong link between serious head injury and future risk of Alzheimer’s, especially when trauma occurs repeatedly or involves loss of consciousness. Protect your brain by buckling your seat belt, wearing your helmet when participating in sports, and “fall-proofing” your home. Learn more about traumatic brain injury.
Heart-head connection: Growing evidence links brain health to heart health. Your brain is nourished by one of your body’s richest networks of blood vessels. Every heartbeat pumps about 20 to 25 percent of your blood to your head, where brain cells use at least 20 percent of the food and oxygen your blood carries.
The risk of developing Alzheimer’s or vascular dementia appears to be increased by many conditions that damage the heart or blood vessels. These include high blood pressure, heart disease, stroke, diabetes and high cholesterol. Work with your doctor to monitor your heart health and treat any problems that arise.
Studies of donated brain tissue provide additional evidence for the heart-head connection. These studies suggest that plaques and tangles are more likely to cause Alzheimer’s symptoms if strokes or damage to the brain’s blood vessels are also present.
Latinos and African-Americans at Risk
Because Latinos and African-Americans in the United States have higher rates of vascular disease, they also may be at greater risk for developing Alzheimer’s. According to a growing body of evidence, risk factors for vascular disease — including diabetes, high blood pressure and high cholesterol — may also be risk factors for Alzheimer’s and stroke-related dementia.
General healthy aging: Other lines of evidence suggest that strategies for overall healthy aging may help keep your brain as well as your body fit. These strategies may even offer some protection against developing Alzheimer’s or related disorders. Try to keep your weight within recommended guidelines, avoid tobacco and excess alcohol, stay socially connected, and exercise both your body and mind. Sign up for Alzheimer’s enews and stay informed on research investigating lifestyle factors and the risk of cognitive impairment.
Copyright © 2014 Alzheimer’s Association®. All rights reserved. |
<urn:uuid:19d97395-e4eb-45f4-aaa0-630a2f2df604> | seed | 1. What is "Emergency Nursing?" Emergency Nursing is a specialty in which nurses care for patients in the emergency or critical phase of their illness or injury and are adept at discerning life-threatening problems, prioritizing the urgency of care, rapidly and effectively carrying out resuscitative measures and other treatment, acting with a high degree of autonomy and ability to initiate needed measures without outside direction, educating the patient and his family with the information and emotional support needed to preserve themselves as they cope with a new reality. These activities may be carried out in a variety of settings and not necessarily in an "Emergency Room."
2. Don't all nurses take care of patients in emergencies? Yes, within their own specialty, nurses should be prepared to take care of foreseeable emergencies. However, Emergency Nurses, are a specialty that spans all others focusing on the time and criticality aspects, as the nurse who first cares for the sudden emergency must be as capable of caring for cancer patients as trauma patients, and of providing "ambulatory care" for lesser or outpatient problems, which have caused a temporary crisis or need for urgent medical care.
3. Isn't "Emergency Nursing" the same as "Trauma Nursing"? Emergency Nursing comprises all aspects of initial critical care whether applied to trauma-originating problems or those of medical or surgical origin or in the treatment of other specialties such as mental health. In those settings, where there is high focus or numbers of trauma patients, that designation has often been found but reflects a sub-specialty narrowing of view or clientele. "Trauma Nurse" has also been used to describe the days or weeks of intensive-care nursing of trauma patients in hospital; yet while these are part of the spectrum of care from injury to recovery, ---it is an "Emergency Nurse" who provides the initial care, resuscitation, and management so that the patient, whether ill or injured, is able to survive to the next phase of his "spectrum of care." [Click for ENA Definition of Emergency Nursing & Society of Trauma Nurses Definition of Trauma Nursing]
4. How is "Emergency Nursing" different from other nursing? An Emergency Nurse is characterized by high degrees of knowledge and skills, with diagnostic and decision-making power to effectuate urgently needed activities in autonomous fashion or in the closely-collaborative team approach with other health professionals. Typically, an Emergency Nurse is capable of providing a broad spectrum of skills that in other settings would be delegated to other health care workers. Without disregarding the critical activities, Emergency Nurses commonly triage and treat less urgent problems, providing care and treatment of those injuries or illnesses, and providing the educational and psychosocial evaluations and support to return the patient successfully to his milieu.
5. Are there other aspects of Emergency Nursing that are different from other nursing specialties? The Emergency Nurse typically works with patients who are not yet diagnosed, may have new problems not previously perceived, is not yet accustomed to the institutional environment, is still struggling to deal with a new reality of illness or injury, who may have an element of uncertainty to their problem, and who may have intoxicants or other behavioral barriers to effective diagnosis or treatment. The Emergency Nurse is at "the front line" of the hospital's contact with the community. The environment and patient situations are dynamic. There is some risk of personal harm from situations that are not yet completely controlled. The Emergency Nurse may need to assess and provide guidance for patients who call for "advice" or who have not yet arrived in the Emergency Department. The Emergency Nurse must also be sensitive and skilled in discerning the patient's educational needs to understand and care for the problem and be a successful and supportive teacher under less-than-ideal conditions. Likewise, the Emergency Nurse must be similarly talented with psychosocial problems and be knowledgeable of available community resources and able to implement them.
6. What is the preparation and training of an Emergency Nurse? Emergency Nursing has drawn nurses from many backgrounds and specialties, and the rich eclecticism this brings gives vitality and useful support for colleagues. Often, there has been a strong medical-surgical, critical-care, or cardiac background, however, with good support new graduates have succeeded in Emergency Nursing. The focus is on broad clinical knowledge, excellent skills, flexible and adaptable approach, and strong inter-personal and teaching ability. Certification courses in adult and child advanced life support, and core-curricula in Emergency Nursing and in Trauma are useful. A good Emergency Nurse continues education and training throughout the career. Advanced degrees are available for those who wish to pursue a career as a Clinical Nurse Specialist or Nurse Practitioner, or who intend to teach or conduct research.
7. Is there a certification of specialty knowledge? CEN or Certified Emergency Nurse is a distinction that may be earned by examination to show possession of a body of knowledge commensurate with competent practice that is awarded by The Board of Certification in Emergency Nursing to qualifying nurses from the USA, Canada, Australia, and New Zealand; BCEN is committed to the vision of international certification. CFRN or Certified Registered Flight Nurse may be earned by those nurses who provide care in the aviation environment.
8. Is there a professional organization for Emergency Nursing? In the United States of America, the professional organization of the specialty is the Emergency Nurses Association. There are other organizations in other countries.
A. What is "Emergency Nursing World !"? ENW is a web-site which was begun by a working emergency nurse to be an Internet resource for emergency nurses throughout the world.
B. What does ENW do? It seeks to provide a world resource for the informational needs of Emergency Nurses, a repository and means of communication for practice-based concerns in emergency nursing, and a forum for sharing and discussing methods or issues among all health professionals involved in the care of emergency patients whether hospital-based or pre-hospital, including in-hospital definitive care specialists.
C. Who can contribute to ENW? Any Emergency Nurse, or professional involved in the care of emergency patients at any point in the spectrum of care, with information to share that is useful to emergency nurses can submit articles and data.
D. Is ENW commercial? No. ENW is non-commercial. It does not accept advertising, provide endorsements, or sell mailing-lists. It receives no subsidies or sponsorship.
E. Is ENW recognized for what it does or is its materials used elsewhere? ENW has received compliments and praise from many individuals. It is linked on a number of other web sites that provide or catalog medical resources on the web. Some articles have been reprinted for training purposes.
F. What is the ENW Emergency Nursing COOL Web-Find? No longer awarded, The Emergency Nursing COOL Web-Find is a Distinction awarded by ENW to exemplary web resources of usefulness to emergency nurses. This is done to feature well-done sites to emergency nurses, to foster the use of the Internet by nurses and emergency nurses, to encourage Internet publishing among nurses and emergency nurses, and to bring awareness of emergency nursing as a potential target audience to providers of medical content on the Internet.
G. How does ENW serve other specialties and professions? ENW serves other specialties as their patients with an emergency or health care episodic need are better served by emergency nurses who are well-informed and can rapidly access the data or resources within those specialties which is needed. ENW serves as a pointer to the best within each specialty and promotes emergency nurses as a target audience. Many occupational groups may be involved in caring for emergency patients and the patient is best served if all involved in his care understand each other and work cooperatively.
H. "I'm doing research on _____" "Do you have statistics on _____?" "Can you advise me on educational plans or how to get a job?" ENW does not have a database of statistics or industry trends. Since the editor is a working nurse, there is little time or means to do such research for others even though I might wish every success to the project. If interesting data are submitted and would be of use or general interest to the readership, ENW will save or post such data if in electronic form [i.e. there is no scanner], or post a link to its Internet availability if copyright protection requires. ENW will provide some links to educational institutions and to job-finding resources, but is unable to provide specific advice in such instances.
I. "I'd like to correspond with a pen pal . . . " No lists or open sources of ENW readership are kept. If there is sufficient interest in maintaining a public list of this sort, ENW will work on one.
J. "Is it possible to reprint an article from ENW ?" Yes, it is often possible to reprint material for nursing and educational purposes. Please e-mail us to find out. Some material, however, may be under the copyright of a different author.
K. "CAL-ENA's web page seems to be at your site; why is that?" In support of CAL-ENA, help has been given in preparing and facilitating its web presence. Each page will maintain separate identity and be responsible only for its own content. Minimal interlinking will be provided for convenience only.
L. "What is the correct way to show ENW's name?" Emergency Nursing World !
There are four elements to ENW's name: Emergency, Nursing, World, and ! representing
Emergency = the nature of the work we do,
Nursing = the professional approach that we bring to it,
World = the setting and variety of it and the global nature of Internet communication,
! = the intensive and imperative nature of our responses to these emergencies.
These elements are italicized (and underlined whenever possible) to emphasize the motion, purposefulness, and energy of our actions.
There is a full space setting off and separating the exclamation mark.
Our color scheme is teal green, gold, and red.
M. "How should I correctly cite ENW as a reference from the Internet when footnoting?" A style acceptable for academic papers would be: Author's Last Name, First Name; Title of Document; URL of Document; Type of Medium; Document date and copyright; Name of Site (if applicable); URL of site if different from above; Accessed Day Month Year
Trimble, Tom, RN
"Action Plan For Airway Hell!"
Web Article from Emergency Nursing World !
June 24, 1998
"The Emergency Nursing FAQ" is provided by
Emergency Nursing World ! [http://ENW.org]
"The Emergency Nursing World ! FAQ" is provided by
Emergency Nursing World ! [http://ENW.org]
©Tom Trimble, RN [[email protected]]
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<urn:uuid:537c4466-10c9-48d7-bce7-3f60849867af> | seed | Frequently Asked Questions About Infertility
What is assisted reproductive technology (ART)?
Assisted reproductive technology (ART) is a term that describes several
different methods used to help infertile couples. ART involves removing eggs
from a woman's body, mixing them with sperm in the laboratory, and putting the
embryos back into a woman's body.
How often is assisted reproductive technology (ART) successful?
Success rates vary and depend on many factors. Some things that affect the
success rate of ART include:
- Age of the partners
- Reason for infertility
- Fertility clinic
- Type of ART
- If the egg is fresh or frozen
- If the embryo is fresh or frozen
The CDC collects success rates on ART for some fertility clinics. According
to the 2003 CDC report on ART, the average percentage of ART cycles that led to
a healthy baby were as follows:
- 37.3% in women under the age of 35
- 30.2% in women aged 35-37
- 20.2% in women aged 37-40
- 11.0% in women aged 41-42
ART can be expensive and time-consuming. But it has allowed many couples to
have children that otherwise would not have been conceived. The most common
complication of ART is multiple fetuses. But this is a problem that can be
prevented or minimized in several different ways.
What are the different types of assisted reproductive technology (ART)?
Common methods of ART include:
- In vitro fertilization (IVF)means fertilization outside of the body. IVF is
the most effective ART. It is often used when a woman's fallopian tubes are
blocked or when a man produces too few sperm. Doctors treat the woman with a
drug that causes the ovaries to produce multiple eggs. Once mature, the eggs
are removed from the woman. They are put in a dish in the lab along with the
man's sperm for fertilization. After 3 to 5 days, healthy embryos are implanted
in the woman's uterus.
- Zygote intrafallopian transfer (ZIFT)or Tubal embryo transfer is similar to
IVF. Fertilization occurs in the laboratory. Then the very young embryo is
transferred to the fallopian tube instead of the uterus.
- Gamete intrafallopian transfer (GIFT)involves transferring eggs and sperm
into the woman's fallopian tube. So fertilization occurs in the woman's body.
Few practices offer GIFT as an option.
- Intracytoplasmic sperm injection (ICSI) is often used for couples in which
there are serious problems with the sperm. Sometimes it is also used for older
couples or for those with failed IVF attempts. In ICSI, a single sperm is
injected into a mature egg. Then the embryo is transferred to the uterus or
ART procedures sometimes involve the use of donor eggs (eggs from another
woman), donor sperm, or previously frozen embryos. Donor eggs are sometimes
used for women who can not produce eggs. Also, donor eggs or donor sperm are
sometimes used when the woman or man has a genetic disease that can be passed
on to the baby. |
<urn:uuid:28f72d55-9729-4886-ad77-046fd6dd186c> | seed | Rotavirus is a leading worldwide cause of acute gastroenteritis in young children. This retrospective hospital-based study assessed the burden of rotavirus gastroenteritis in children younger than 6 years in Japan.
Children admitted to eight hospitals for acute gastroenteritis between 2008 and 2009 were identified from hospital admission databases. Diagnosis of acute gastroenteritis/rotavirus gastroenteritis and hospital-acquired rotavirus gastroenteritis was confirmed based on either the International Classification of Diseases and Related Health Problems 10th revision (ICD10) codes (intestinal infectious diseases [AA00-AA09] and rotavirus gastroenteritis [A08.0]) or from rapid rotavirus diagnostic test results.
Of 13,767 hospitalized children, 11.9% (1,644), 4.8% (665) and 0.6% (81) were diagnosed with acute gastroenteritis, rotavirus gastroenteritis and hospital-acquired rotavirus gastroenteritis, respectively. Among acute gastroenteritis hospitalizations, 40.5% (665/1,644; ICD10 and rapid test) and 57.7% (645/1,118; rapid test only) were confirmed as rotavirus positive. Of 1,563 children with community-acquired acute gastroenteritis, 584 (37.4%) cases were confirmed as rotavirus positive. The median durations of hospitalization for all and community-acquired rotavirus gastroenteritis were 5.0 days (range: 2.0−133.0 days) and 5.0 days (range: 2.0-34.0 days), respectively. Among rotavirus gastroenteritis hospitalizations, 12.2% (81/665) of cases were hospital-acquired and the median duration of hospitalization was 10.0 days (range: 2.0-133.0 days). The median duration of additional hospitalization due to hospital-acquired rotavirus gastroenteritis was 3.0 days (range: 0–14 days). The overall incidence rate of hospital-acquired rotavirus gastroenteritis was 1.0 per 1,000 children hospital-days. The number of rotavirus gastroenteritis cases peaked between February and May in both 2008 and 2009, and the highest number of cases was reported in March 2008 (21.8%; 145/665). The highest number of rotavirus gastroenteritis hospitalizations (24.1%; 160/665) was observed in children aged 12–18 months. The proportion of hospital-acquired rotavirus gastroenteritis was higher in children aged below 18 months as compared to children at least 18 months of age (0.94 [95% CI: 0.71-1.21] vs. 0.39 [95% CI: 0.25-0.58]) and for children hospitalized for at least 5 days compared to those hospitalized for less than 5 days (0.91 [95% CI: 0.72-1.14] vs. 0.15 [95% CI: 0.05-0.32]).
Both community- and hospital-acquired rotavirus gastroenteritis are significant public health problems in Japan. Data from this study justify the need for the introduction and implementation of rotavirus vaccination in the Japanese national immunization program.
Keywords:Children; Epidemiology; Gastroenteritis; Japan; Hospital-acquired; Rotavirus
Rotavirus (RV) is the most common etiological cause of acute gastroenteritis (GE) resulting in hospitalization among young children throughout the world . In Japan, the burden of RVGE disease is substantial, with approximately 800,000 children aged below 6 years visiting clinics and hospital outpatient departments annually. A previous study conducted in Japan reported an overall incidence of outpatient visits of 11 cases per 100 person-years due to RVGE in children less than 6 years of age; the highest incidence (27 cases per 100 person-years) was observed in infants . In another single-center study conducted between 2008 and 2010 in Kyoto, the proportion of children aged below 5 years diagnosed with RVGE was reported to be 56% . Although episodes of RVGE can potentially be severe , due to a low mortality rate associated with RVGE in Japan, local awareness of the disease is low. Nevertheless, in Japan, RVGE is a common cause of acute GE hospitalizations whether community- or hospital-acquired and results in significant clinical and economic burden .
There are no official, evidence-based guidelines on the treatment of pediatric acute GE in Japan , but RVGE is most commonly managed using intravenous fluid replacement therapy . Prophylactic interventions, such as RV vaccination, may represent an effective primary public health strategy to reduce the burden of RVGE . Two orally administered RV vaccines, which have demonstrated good efficacy and safety profiles in global clinical trials, have been licensed in most countries: Rotarix™ (GlaxoSmithKline Vaccines, Belgium) and RotaTeq® (Merck and Co., Inc., Whitehouse Station, NJ, USA) [8,9]. In 2009, the World Health Organization (WHO) recommended the inclusion of RV vaccines in the routine childhood vaccine programs of all countries .
The objectives of this study were to estimate the burden of overall acute GE, RVGE and hospital-acquired RVGE in hospitalized children younger than 6 years of age, as well as to assess the age and seasonal distributions; and duration of hospitalization and additional hospitalization associated with hospital-acquired RVGE. Our findings could have important implications for the introduction of routine RV vaccination into the Japanese national immunization program. Furthermore, up to-date epidemiological data on RVGE disease may help evaluate the impact and cost-effectiveness of RV vaccination programs in Japan.
This retrospective, multi-center epidemiological study was conducted between January 2008 and December 2009 at eight regional core hospitals in the urban areas of Japan, which represented an optimum geographic coverage (Figure 1). All study hospitals treated pediatric infectious diseases including acute GE, and were included if they had at least 15 pediatric inpatient beds (range in the study hospitals 16–50) and routinely tested for the presence of RV using rapid tests. At each hospital, one nurse was allocated to either seven or ten children and participating hospitals provided primary, secondary and tertiary emergency care for children .
Figure 1. Geographic distribution of the participating hospitals, 2008–09.
Children aged less than 6 years, who were hospitalized for acute GE or RVGE during the survey period, were included in the study. These children were identified through the electronic hospital databases. Diagnosis of acute GE/RVGE and hospital-acquired RVGE was confirmed either according to the International Classification of Diseases and Related Health Problems 10th revision (ICD 10) codes (intestinal infectious diseases [AA00-AA09] and RVGE [A08.0]) or based on the results from rapid RV diagnostic tests, using immune-chromatography (RapidTesta®ROTA-ADENO, Orion Diagnostica; Bioline SD Rota/Adeno Rapid, Standard Diagnostics, INC, Kyonggi, Korea; BD Rota/Adeno Examan™ stick, Becton, Dickinson & Co; and Premier™ Rotaclone®, Meridian Bioscience, Inc, Ohio, USA).
Acute GE was based on the ICD 10 codes for intestinal infectious diseases: with occurrence of diarrhea for less than 14 days. Community-acquired RVGE was defined as RVGE hospitalization other than hospital-acquired RVGE. Hospital-acquired RVGE was defined as occurrence of RVGE at least 48 hours after hospital admission or within 48 hours after hospital discharge. For a child who was hospitalized for acute GE within the last 48 hours investigators ascertained the presence of RV from the medical chart. RV tests were not performed in hospitals for subjects who had already been diagnosed with RVGE at other clinics or hospitals, since the variance of diagnosis intensity depended on subjects and not on the participating hospitals.
Medical histories were collected from medical charts or the hospital database, and the duration of hospitalization for acute GE and community-acquired RVGE, define as the number of days between the date of admission and date of discharge, was automatically calculated in the medical chart database. The duration of additional hospitalization for hospital-acquired RVGE (in days) was estimated as the difference between the usual average number of days spent in hospital due to the specific medical condition and the number of days the child actually spent in hospital.
This study was conducted in compliance with Good Clinical Practice (GCP) guidelines and the Japanese Ministry of Health, Labor and Welfare’s (MHLW) ethical guidelines for epidemiological research. Since this was an observational survey using hospital database data, informed consent was not obtained from the enrolled subjects. This is in accordance with the Japanese ethical guidelines for epidemiological research. All the relevant documents were reviewed by the ethical committees and ethical approval was sought from each of the participating hospitals.
Endpoints and statistical analysis
All analyses were descriptive and the demographic distribution of children aged below 6 years who were hospitalized with acute GE, RVGE and hospital-acquired RVGE were presented. The overall proportions of acute GE, RVGE and hospital-acquired RVGE among all the subjects and proportions of hospital-acquired RVGE stratified by hospital and patient characteristics were estimated with 95% confidence intervals (CI) using the Exact Method . Median duration of hospitalization (in days) due to RVGE, community-acquired RVGE and hospital-acquired RVGE, and the median duration of additional hospitalization due to hospital-acquired RVGE were estimated. The incidence of hospital-acquired RVGE was calculated by dividing the number of hospital-acquired RVGE cases by the total number of hospital days among all at-risk children and was expressed per 1000 hospital days. When estimating incidence, 95% CI was calculated using Poisson’s method. All statistical analyses were performed using SAS version 9.2.
Among 13,767 hospitalized children, 1,648 were diagnosed with acute GE and were included in the study, of whom four were excluded from the final analysis as they did not meet the inclusion criteria. The demographic characteristics of the 1,644 (11.9%) children included in the final analysis are shown in Table 1.
Table 1. Demographic characteristics of children aged less than 6 years, hospitalized in Japan during 2008–09
Among the 1,644 children with acute GE, 665 (40.5%) were confirmed with RV, using either ICD 10 diagnostic codes or RV diagnostic tests. The proportion of overall RVGE among all hospitalized children aged less than 6 years was therefore 4.8% (665/13,767). RV diagnostic testing, performed on stool samples from 1,118 children (68.0%) with acute GE, confirmed that 645 (57.7%) were RV-positive. Of the 1,563 children with community-acquired acute GE, 584 (37.4%) were RV-positive. Eighty-one of the 665 RV-positive cases, (12.2%) were confirmed as hospital-acquired RVGE. Similar proportions of RVGE (overall and hospital-acquired) were observed in children aged less than 5 years (Table 2). Underlying medical conditions were present in 159 cases (9.7%) of acute GE hospitalizations, 59 cases (8.9%) of RVGE hospitalizations and 22 cases (27.2%) of hospital-acquired RVGE cases (Table 1).
Table 2. Proportion of RVGE diagnosed in hospitalized children (ICD10 codes and RV rapid test kits) in Japan during 2008–09
Cumulative age distributions of acute GE and RVGE hospitalizations are shown in Figure 2. Three cases of RVGE were reported in infants aged below 1 month. The highest proportion of acute GE and RVGE hospitalizations were observed in children aged 12–18 months (20.2% [332/1,644] and 24.1% [160/665], respectively), followed by children aged 6–12 months (18.0% [296/1,644] and 16.6% [110/665], respectively).
Figure 2. Age distribution of acute GE, RVGE hospitalizations and hospital-acquired RVGE cases.
The median duration of hospitalization for all RVGE and community-acquired RVGE was 5.0 days (range: 2.0−133.0 days) and 5.0 days (range: 2.0−34.0 days). The longest duration of hospitalization due to all RVGE (median 9.0 days [range: 5.0−108.0 days]) was observed in children aged 5–6 months (n/N= 7/665).
The number of RVGE cases peaked between February and May in both 2008 and 2009 and the highest number of cases (21.8%; 145/665) was recorded in March 2008.
Among the children aged below 6 years who were hospitalized, the overall proportion of hospital-acquired RVGE was estimated to be 0.6% (N=81; 95% CI: 0.5−0.7) (0.9% [95% CI: 0.7−1.1] in 2008 and 0.3% [95% CI: 0.2−0.5] in 2009). Across the hospitals, the proportions of hospital-acquired RVGE ranged from 0.1% (95% CI: 0.0−0.7) to 1.7% (95% CI: 1.1−2.6). The overall incidence of hospital-acquired RVGE was 1.0 per 1,000 person-days (95% CI: 0.8−1.2) in children aged less than 6 years (1.4 [95% CI: 1.1−1.8] in 2008 and 0.5 [95% CI: 0.3−0.8] in 2009). The highest number of hospital-acquired RVGE cases was observed in children aged 12–18 months (27.2%; 22/81), followed by those aged 0–6 months (23.4%; 19/81) and 6–12 months (19.7%; 16/81) (Figure 2). All three cases of RVGE in infants aged below 1 month and 50.0% (3/6) of cases in children aged less than 2 months were hospital-acquired. A decreasing trend of hospital-acquired RVGE among RVGE hospitalizations with age was observed, with higher proportions being reported in younger children (especially in infants aged below 1 month) (Figure 2).
The median duration of hospitalization for hospital-acquired RVGE cases was 10.0 days (range: 2.0−133.0), but varied according to the presence of different medical conditions: gastrointestinal disease (26.0 days [range: 26.0−26.0]); neurological disease (108.0 days [range: 23.0−133.0]); prematurity (31.0 days [25.0−37.0]); pulmonary disease (10.0 days [range: 7.0−15.0]); and others (20.5 days [range: 12.0−89.0]). In subjects without any underlying medical condition, the median duration was 9.0 days (range: 2.0−43.0). The median duration of hospitalization for children with hospital-acquired RVGE also varied by hospital and ranged from 6.5 days (range: 4.0−15.0) to 20.5 days (range: 15.0−26.0). The median duration of additional hospitalization as a result of hospital-acquired RVGE was 3.0 days (range: 0.0–14.0).
The proportion of hospital-acquired RVGE was higher in children aged below 18 months as compared to children at least 18 months of age (0.94 [95% CI: 0.71−1.21] vs. 0.39 [95% CI: 0.25−0.58]) and for children hospitalized for at least 5 days compared to those hospitalized for less than 5 days (0.91 [95% CI: 0.72−1.14] vs. 0.15 [95% CI: 0.05−0.32]). The proportions of hospital-acquired RVGE were also estimated to be higher in hospitals: with an allocation of one nurse per seven patients compared to those with an allocation of one nurse per ten patients (0.74 [95% CI: 0.56−0.95] vs. 0.18 [95% CI: 0.04−0.54]); with at least 30 beds compared to fewer than <30 beds (0.74 [95% CI: 0.58−0.92] vs. 0.53 [95% CI: 0.34−0.79]); and in hospitals with an isolation ward (0.75 [0.59−0.94] vs. 0.24 [95% CI: 0.08−0.56]) compared to hospitals without an isolation ward) (Table 3). Among all the children with RVGE and an underlying medical condition 37.3% (22/59) cases were hospital-acquired RVGE compared to only 9.7% (59/606) of cases in children who did not have any underlying medical condition.
Table 3. Characteristics of hospital-acquired RVGE in children aged below 6 years in Japan during 2008–09 (N=13767)
The present study is one of the largest multicenter hospital-based studies conducted in Japan that describes the burden of RVGE disease, including hospital-acquired RVGE in pre-school children. The findings of this study estimate that 4.8% of all hospitalizations in children aged below 6 years are due to RV. Despite the retrospective study design, 68.0% of hospitalizations due to acute GE were tested for the presence of RV of which 57.7% cases were RV-positive with the median duration of hospitalization of 5.0 days. These observations are consistent with previously published data on RVGE from Japan . In this study, the highest burden of hospitalized RVGE disease was observed in children younger than 2 years of age, which is similar to that reported from several observational studies conducted in Europe [12-15]. The occurrence of RVGE usually exhibits a seasonal pattern and in this study, a peak in the number of RVGE cases was observed between February and May in both 2008 and 2009. The highest number of RVGE cases was observed in March, suggesting that in line with previous reports, RVGE is a common disease in Japan until early summer and is no longer winter-specific [17,18].
We found that the proportion of hospital-acquired RVGE among all hospitalizations of children aged less than 6 years was 0.6% and was associated with median duration of additional hospitalization of 3 days. This proportion was well within the range that was observed in children below 5 years in the European Union (0.3−27.7%) . We believe that this relatively low proportion of hospital-acquired RVGE could be due to different infection control procedures in the Japanese healthcare system . However, there are no differences between Japanese and European hospitals and the reason for this apparent difference remains to be unknown. The incidence of hospital-acquired RVGE of 1.0 per 1,000 hospital-days reported in our study was well within the range (0.0−1.87 per 1,000 days of hospitalization) reported in Europe by Forster et al. . In other observational studies conducted across Europe, it was reported that 95.7% of all hospital-acquired RVGE cases occurred in children younger than 2 years of age . Our results also recorded higher proportions of hospital-acquired RVGE in children below 2 years of age compared with older children. The median duration of addition hospitalization due to hospital-acquired RVGE of 3.0 days which we observed was slightly lower than the mean duration of hospitalization (4.7 days) in infectious disease wards among children aged 1–4 years in Japan .
This study provides signs of patient and hospital characteristics that may be associated with the occurrence of hospital-acquired RVGE. Patient characteristics such as duration of hospitalization, age, prematurity or low birth-weight, severe immuno-deficiencies and absence/presence of underlying medical conditions have been previously reported as risk factors for hospital-acquired RV infection . Indeed, in our study children with underlying medical conditions had a higher proportion of hospital-acquired RVGE compared to children without these conditions. We found higher proportions of hospital-acquired RVGE in children aged below 18 months and in those who were hospitalized for at least 5 days compared to those aged at least 18 months or hospitalized for fewer than 5 days, respectively. Children younger than 18 months of age may be more susceptible to hospital-acquired RVGE as well as need more attention from caregivers and may therefore be more likely to acquire RV infection from them. The proportions of hospital-acquired RVGE were higher in children at hospitals with a nurse allocation of one per seven patients than at hospitals with an allocation of one per ten patients, and also in hospitals with an isolation ward/room. The observation associated with higher nurse allocation may be related to the fact that nurses may be considered as reservoirs of RV infection. However, this study was not designed specifically to study the association of hospital characteristics and occurrence of hospital-acquired RVGE, presented in previous studies , therefore the clinical implications of these data need to be interpreted with caution.
The direct medical cost of a single hospitalization with a mean duration of hospitalization of 5.4 days due to RVGE in Japan has been estimated to be 1,888 US$ (221,000 JPY; 1 US$ = 83.6 JPY ) . Considering the median duration of a single RVGE hospitalization of 5.0 days in this study, the direct medical cost per RVGE case per day is estimated to be 378 US$. Accordingly, the direct medical cost for an additional 3.0 days of hospitalization due to hospital-acquired RVGE in this study is estimated to be 875 US$ per hospital-acquired RVGE case. By extrapolating data from Nakagomi et al. , 78,000 RVGE hospitalizations were estimated in Japan per year among children aged below 5 years, of which 12.4% (9,672/78,000) could be considered as hospital-acquired RVGE cases per year. Therefore, the nationwide cost for hospital-acquired RV infection is estimated to be as high as 8,466,341 US$ per year in Japan.
There are several reasons why the results of this study may be applied to the general Japanese pediatric population below 6 years of age hospitalized for acute GE. This is the largest multi-hospital study yet conducted, including 8 hospitals across Japan capturing ~0.5% of the total RVGE hospitalizations that are expected to be reported in children younger than 6 years of age every year . In addition, this study obtained laboratory confirmation using rapid RV diagnostic testing for 68.0% of all acute GE cases, which minimized the possible misclassification of RVGE. The data from this study allow for real world estimates of hospital-acquired RVGE and the duration of additional hospitalization due to hospital-acquired RVGE. Indeed, the hospital databases used in this study confirmed the good quality and diagnostic accuracy. Moreover, the data reported here are consistent with previous studies [3,7,23].
Besides the inevitable limitations of all retrospective surveillance studies , several specific limitations also need to be considered when interpreting the results of this study. Some of the RVGE cases did not have a RV rapid test recorded in the medical chart (~32%), which we believe was due to the fact that testing for the presence of RV may have been conducted previously in other clinics or hospitals. However, these subjects had the specified ICD 10 code for RVGE recorded in hospital database. Furthermore, the number of hospital-acquired RVGE cases may have been underestimated in this study due to missing ICD 10 codes for some RVGE cases and the difficulty of capturing data on the onset of hospital-acquired RVGE within 48 hours of discharge from hospital, unless the children returned to the participating hospitals for subsequent treatment. Since this was a retrospective database study, no diagnostic criteria were used as confirmation of diagnosis. The diagnosis was based on clinical practice and results of the RV diagnostic rapid tests were taken from the medical charts. Our method of determining median duration of additional hospitalization for hospital-acquired RVGE did not take into account the potential impact of accompanying chronic medical conditions and this may thus limit the generalizability of our findings. Another limitation of the present analysis is that although subjective, the duration of additional hospitalization for hospital-acquired RVGE was estimated based on careful examination of the medical chart and prescription record by comparing the duration of hospitalization for the specific case and the usual average duration of hospitalization for certain diseases if not associated with RVGE. However, duration of additional hospitalization was estimated as zero if medical chart review revealed that RV was unlikely to have had any impact on hospitalization duration (e.g. duration of hospitalization due to primary diagnoses was too long and hospital-acquired RVGE occurred in the middle of hospitalization for initial diagnoses etc.). Finally, the incidence calculated in this study may have been underestimated since the incubation period for hospital-acquired RV infection was not taken into account.
The results of this large, multicenter study conducted in Japanese hospitals suggest that RV is a major cause of acute GE disease in children younger than 6 years of age and leads to a substantial burden on the public healthcare system in Japan. These results warrant further investigation into the need for implementing RV vaccination into the national immunization program of Japan. The baseline data from this study will be useful when assessing the impact and cost-effectiveness of future RV vaccination programs.
RV: Rotavirus; GE: Gastroenteritis; ICD 10: International Classification of Diseases and Related Health Problems 10th revision; CI: Confidence interval.
Hitoshi Tajiri, Toshihiro Ohura, Hisashi Kawashima, Kosuke Ushijima, Tomoko Takano and Shigeru Toyoda received institutional grants and consultation fees from GlaxoSmithKline group of companies for this study. Ayano Inui, Kimie Yamamoto, Yoshihito Higashidate, received institutional grants from GlaxoSmithKline group of companies for this study. Shigeru Toyoda received a lecture fee from the sponsoring company for activities outside this current publication. Katsiaryna Holl and Gunasekaran Ramakrishnan are employees of GlaxoSmithKline group of companies. Mats Rosenlund and Yuriko Takeuchi were employees of GlaxoSmithKline group of companies and GlaxoSmithKline Japan, respectively at the commencement of this study.
HT, YT, TT, TO, AI, KY, YH, HK, ST, KU, MR and KH took part in either the conception and design of the study, protocol development, study results analysis and interpretation and/or collection of the data. GR performed the statistical data analyses. All authors reviewed and commented on the draft manuscript, and all authors read and approved the final manuscript.
The authors would like to thank the following from GlaxoSmithKline group of companies: Nadia Meyer for critically reviewing manuscript content, Hisao Muto, Vinod Ramesh and Kusuma Gopala for their contributions to the study and Satabdi Mukherjee and Ashmita Ravishankar for medical writing. Satabdi Mukherjee was an employee of GlaxoSmithKline group of companies. We also like to thank Amrita Ostawal (consultant publications writer to GlaxoSmithKline group of companies), and Roeland Van Kerckhoven (Keyrus Biopharma) for editorial assistance and manuscript coordination on behalf of the GlaxoSmithKline group of companies.
Sources of support
This study (NCT01202201) was funded by GlaxoSmithKline Biologicals SA.
Rotarix is a registered trademark of GlaxoSmithKline group of companies.
RotaTeq is a registered trademark of Merck and Co., Inc., USA.
RapidTesta Rota Adeno is a registered product of SEKISUI MEDICAL CO., LTD. Immunocard ST Rotavirus is manufactured by TFB, INC.
BD Rota/Adeno stick is manufactured by Becton, Dickinson & Co.
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The pre-publication history for this paper can be accessed here: |
<urn:uuid:89075ad8-059d-4ed1-944c-9699428ce32f> | seed | Addition of Chemotherapy to Radiotherapy Continues to Increase Survival in People with Brain Tumors
Giving people with glioblastoma the chemotherapy drug temozolomide in combination with radiotherapy increases their survival compared with those receiving radiotherapy alone, and this improvement persists for up to five years, according to the final results of the EORTC-NCIC trial, published in The Lancet Oncology. For over 30 years, post-operative radiotherapy was the standard treatment for glioblastoma, but it offered only modest survival benefits. The average life-expectancy of people with glioblastoma was 9 to 12 months.
In 2004, after many disappointing attempts with drug therapy, the EORTC-NCIC trial finally showed some promising results, where use of combined treatment with radiotherapy and temozolomide reduced the risk of dying from glioblastoma by 37 percent compared with radiotherapy alone. At two years, 27 percent of people receiving temozolomide in combination with radiotherapy (TMZ/RT) were alive, compared with just 10 percent of those being treated with radiotherapy (RT) alone. However, whether this survival benefit would persist over time was unknown.
In this study, Roger Stupp and colleagues report the five-year outcomes of those involved in the original EORTC-NCIC trial. The authors also examined whether clinical factors and the molecular profile of the tumors would identify people with particularly good survival or response to chemotherapy.
Findings showed that at three years, 16 percent of those receiving TMZ/RT were alive compared with only 4 percent of people having RT alone. At four years, overall survival data after combined treatment were 12.1 percent compared with 3 percent for RT alone, and at five years, 9.8 percent versus 1.9 percent, respectively. Improvement in survival was seen across all clinical prognostic subgroups, even in people considered to have a poor diagnosis.
In exploratory analyses, overall survival data were best in people being treated with TMZ/RT whose tumors carried an inactivated MGMT gene. Almost half of these people were alive after two years, and they also showed a persistent survival advantage at three, four, and five years. The authors suggest that testing tumors for the methylation status of the MGMT gene would allow the selection of those most likely to benefit from this treatment.
The authors caution that upfront combined therapy may be effective in reducing tumor bulk and aggressiveness, but it does not truly modify the natural behavior of the disease, and thus is unlikely to lead to a cure.
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This article was published in Coping® with Cancer magazine, May/June 2009. |
<urn:uuid:3e4354e1-61cc-40c7-b50c-731154d518eb> | seed | Over 20 million people in the United States (about 8% of the population) have type 2 diabetes.1 Worldwide prevalence of diabetes in adults is about 6%, and Asian countries have somewhat higher rates (9% in China and Korea, and 11% in Japan).2,3 This is interesting to consider. In spite of considerably more overweight and obesity in the USA and our dangerous diet, there is considerably more diabetes in China, Korea and Japan. This is mostly because of white rice.
Type 2 diabetes arises out of insulin resistance, a state in which the body’s cells cannot respond properly to insulin – a hormone that allows for the transport of glucose into the body’s cells and storage of the energy contained in that glucose. Carrying excess fat and eating high glycemic load (GL) foods contribute to the development of insulin resistance (and of course, eating high glycemic foods contributes to weight gain).
Refined carbohydrates like white rice, devoid of fiber to slow down absorption of sugars, raise blood glucose more and faster than their intact, unprocessed counterparts. The effect of a food on blood glucose is indicated by its glycemic index (GI) – a 1-100 measure of the blood glucose response per gram of carbohydrate. Glycemic load (GL), a related indicator, takes into account both the GI and the carbohydrate content of a typical portion size.
A new meta-analysis has explored the link between white rice and diabetes
An analysis of four prospective studies on white rice consumption and diabetes has recently been published – it included 2 studies in Asian populations and 2 in Western populations. In Asian countries, where white rice is a staple food, the average intake of white rice was 3-4 servings per day, and in Western countries the average was 1-2 servings per week. A comparison of the highest vs. lowest white rice intake groups yielded a 55% increase in diabetes risk in Asians, and a 12% increase in Westerners. Overall, the researchers found that each daily serving of white rice increased the risk of diabetes by 11%.4
This new research serves to remind us: High-glycemic, nutrient-depleted, refined carbohydrates (like white rice) are more than just empty calories – they are disease-causing foods.
Westerners on average ate less than one daily serving white rice – but what about the other high-GL foods that Americans eat daily? White pasta, white potato, and white bread are also high in GL and therefore likely to be just as dangerous. It’s no wonder that U.S. diabetes rates have tripled in the past 30 years, and are expected to double or even triple by 2050.2
(High = 20 and above; Low = 1-10)
|White potato (1 medium baked)||29|
|White rice (1 cup cooked)||26|
|White bread (1 bagel, 3.5 in. diameter)||24|
|White pasta (1 cup cooked)||21|
|Chocolate cake (1/10 box cake mix + 2T frosting)||20|
|Black rice (1 cup cooked)||14|
|Butternut squash (1 cup cooked)||8|
|Green peas (1 cup cooked)||8|
|Lentils (1 cup cooked)||8|
|Black beans (1 cup cooked)5||6|
Indeed, more and more research is demonstrating potato consumption is associated with diabetes, and this association was found to be most likely due to glycemic load (not due to preparation or added fats). Substituting 1 serving of whole grains per day with potatoes was estimated to increase diabetes risk by 30%.6 Also, in a 6-year study of 65,000 women, those with diets high in refined carbohydrates from white bread, white rice, and pasta were 2.5 times as likely to be diagnosed with type 2 diabetes compared to those who ate lower-GL foods such as intact whole grains and whole wheat bread.7
Not just diabetes – cancer too
High GL foods have dangers that reach beyond diabetes. Diets including large quantities of high GL foods increase the risk of several chronic diseases including diabetes, heart disease, and cancers.8 Let’s make it clear: white rice, white flour products, and white potatoes are foods that should not be central in our diets. Low-nutrient, high glycemic foods are not only unfavorable from the perspective of weight gain and diabetes, but could also contribute significantly to cancer by causing excessive insulin secretion. High insulin levels in the blood can promote the growth of cancer cells, in part by interacting with the receptor for insulin-like growth factor 1 (IGF-1).9 A recent study of Korean women found that each daily serving of white rice increased breast cancer risk by 19%.10 Similarly, a recent U.S. study found a link between starch consumption and breast cancer recurrence.11 Diabetics are 30% more likely to develop colorectal cancer, 20% more likely to develop breast cancer, and 82% more likely to develop pancreatic cancer than non-diabetics. This increased risk of cancer observed in diabetics is thought to be due in part to cancer-promoting effects of insulin therapy.12,13
In the past, white rice was looked upon as a healthful, low fat staple in a vegetarian diet. We have progressed in knowledge and science and it is clear that white rice can no longer be considered healthful, or even neutral – it is a disease-causing food. The damaging effects of high-GL foods have been brought to light, and we now know that the most healthful carbohydrate sources are those that minimize glycemic effects – beans, peas, intact whole grains, and starchy vegetables.
1. American Diabetes Association: Diabetes statistics [http://www.diabetes.org/diabetes-basics/diabetes-statistics/]
2. World Health Organization. Diabetes Fact Sheet. [http://www.who.int/mediacentre/factsheets/fs312/en/ ]
3. IDF Diabetes Atlas: Fifth Edition. International Diabetes Federation; 2011.
4. Hu EA, Pan A, Malik V, et al: White rice consumption and risk of type 2 diabetes: meta-analysis and systematic review. BMJ 2012;344:e1454.
5. Atkinson FS, Foster-Powell K, Brand-Miller JC: International tables of glycemic index and glycemic load values: 2008. Diabetes Care 2008;31:2281-2283.
6. Halton TL, Willett WC, Liu S, et al: Potato and french fry consumption and risk of type 2 diabetes in women. Am J Clin Nutr 2006;83:284-290.
7. Salmeron J, Manson JE, Stampfer MJ, et al: Dietary fiber, glycemic load, and risk of non-insulin-dependent diabetes mellitus in women. JAMA 1997;277:472-477.
8. Barclay AW, Petocz P, McMillan-Price J, et al: Glycemic index, glycemic load, and chronic disease risk--a meta-analysis of observational studies. Am J Clin Nutr 2008;87:627-637.
9. Gallagher EJ, LeRoith D: The proliferating role of insulin and insulin-like growth factors in cancer. Trends Endocrinol Metab 2010;21:610-618.
10. Yun SH, Kim K, Nam SJ, et al: The association of carbohydrate intake, glycemic load, glycemic index, and selected rice foods with breast cancer risk: a case-control study in South Korea. Asia Pac J Clin Nutr 2010;19:383-392.
11. Emond JA, Patterson RE, Pierce JP: Change in Carbohydrate Intake and Breast Cancer Prognosis. In San Antonio Breast Cancer Symposium, vol. Presentation #P3-09-01; 2011.
12. Pollak M, Russell-Jones D: Insulin analogues and cancer risk: cause for concern or cause celebre? Int J Clin Pract 2010;64:628-636.
13. Experts call for further research into the relationship between insulin therapy and cancer. 2010. EurekAlert! http://www.eurekalert.org/pub_releases/2010-03/w-ecf030210.php. Accessed October 20, 2011. |
<urn:uuid:5b730dd9-3201-4adf-ba91-5931863500e9> | seed | What are electrophysiology studies?
Electrophysiology studies (EPS) are tests that help doctors understand the nature of abnormal heart rhythms (arrhythmias).
- Electrophysiology studies test the electrical activity of your heart to find where an arrhythmia (abnormal heartbeat) is coming from.
- These results can help you and your doctor decide whether you need medicine, a pacemaker, an implantable cardioverter defibrillator (ICD), cardiac ablation or surgery.
- These studies take place in a special room called an electrophysiology (EP) lab or catheterization (cath) lab while you are mildly sedated.
When someone’s heart doesn’t beat normally, doctors use EPS to find out why. Electrical signals usually travel through the heart in a regular pattern. Heart attacks, aging and high blood pressure may cause scarring of the heart. This may cause the heart to beat in an irregular (uneven) pattern. Extra abnormal electrical pathways found in certain congenital heart defects can also cause arrhythmias.
During EPS, doctors insert a thin tube called a catheter into a blood vessel that leads to your heart. A specialized electrode catheter designed for EP studies lets them send electrical signals to your heart and record its electrical activity.
Doctors use EPS to see:
- Where an arrhythmia is coming from.
- How well certain medicines work to treat your arrhythmia.
- If they should treat a problem by destroying the place inside your heart that is causing the abnormal electrical signal. This procedure is called catheter ablation.
- If a pacemaker or implantable cardioverter defibrillator (ICD) might help you.
- If you are at risk for heart problems such as fainting or sudden cardiac death due to cardiac arrest (when your heart stops beating).
What are the risks of EPS?
Risks may include:
- Arrhythmia. During EPS you may have abnormal heart rhythms that make you dizzy. If this happens, your doctor may give your heart an electric shock to bring back a regular heartbeat.
- Blood clots sometimes can form at the tip of the catheter, break off and block a blood vessel. Your doctor may give you medicine to prevent blood clots.
- Infection, bleeding and bruising at the site where the catheter went in (groin, arm or neck). Your doctor or nurse will help you avoid these problems.
- Don’t eat or drink anything for 6 to 8 hours before the test.
- Tell your doctor about any medicines you take, including over-the-counter medicines, herbs and vitamins. He or she may ask you not to take them before EPS. Don’t stop taking your medicine until your doctor tells you to.
- Have someone drive you to your appointment and take you home.
- If you usually wear a hearing aid, wear it during your procedure. If you wear glasses, bring them to your appointment.
At a hospital or clinic, doctors and nurses do EPS in a room that has special equipment for the tests. You may hear this room called the electrophysiology laboratory, or EP lab. Some call it the catheterization laboratory (cath lab). During the test:
- A nurse will put an IV (intravenous line) in your arm. You’ll get medicine (a sedative) that will calm youhelp you relax. But you’ll be awake and able to follow instructions during the test.
- Your nurse will clean and shave the part of your body where the doctor will be working. This is usually in the groin but may be the arm or neck.
- You’ll be given a shot – aA local anesthetic will be given — to make the area numb. Your doctor will make a needle puncture through your skin and into your blood vessel. A small straw-sized tube called a sheath will be inserted into your artery or vein. The doctor will gently guide several specialized EP catheters into your blood vessel through the sheath and advance them to your heart. A video screen will show the position of the catheters. You may feel some pressure in the area where the sheath was inserted, but you shouldn’t feel any pain.
- Your doctor will send small electric pulses through the catheters to make your heart beat at different speeds. You may feel your heart beat stronger or faster.
- Electrical signals produced by your heart will be picked up by the special catheters and recorded. This is called cardiac mapping and allows the doctor to locate where arrhythmias are coming from,
- Your doctor will remove the catheters and the IV line. Your nurse will put pressure on the puncture site to stop any bleeding.
- EPS usually last 1 to 4 hours.
“I could feel my heart speeding up, which was weird. But it didn’t hurt. It was more like hiking up and down hills really fast.” Esmerelda, age 38
What happens after EPS?
You’ll be moved to a recovery room where you should rest quietly for 1 to 3 hours. During this time:
- Stay still as long as your nurse tells you to. Be sure to keep the arm or leg used for the test straight.
- Your nurse will check on you often to see if there is bleeding or swelling at the puncture site.
- After the sedative wears off, your doctor will talk to you about your test results.
- Before you leave, you’ll be told what to do at home.
Follow the instructions your nurse or doctor gave you, including taking any new medicines that were prescribed. Most people can start eating food and taking their medicines within 4 to 6 hours after the test. Most can do their usual daily activities the day after the test. Don’t drive for at least 24 hours.
The puncture site may be sore for several days. A small bruise at the puncture site is normal. If the site starts to bleed, lie flat and press firmly on top of it. Have someone call the doctor or EP lab.
What should I watch for?
Call 9-1-1 if you notice:
- A sudden increase in swelling around the puncture site.
- Bleeding doesn’t slow down when you press hard on the site.
- Your arm or leg that was used for the sheath feels numb or tingles.
- Your hand or foot feels very cold or changes color.
- The puncture site looks more and more bruised.
- The puncture site begins to swell or fluids begin to come from it.
Most of the time, doctors will ask you to make an appointment to discuss the results of your test. You’ll discuss your treatment at that appointment.
How can I learn more about EPS?
Talk with your doctor. Here are some good questions to ask:
- Are there medicines that I can use to control my abnormal heartbeats?
- Will I need a pacemaker or implantable cardioverter defibrillator (ICD) now or in the future?
- What caused my irregular heartbeat?
- Am I at risk of serious heart rhythm problems in the future?
This content was last reviewed on 10/23/2014. |
<urn:uuid:735d9db5-7267-4a33-805d-de302f0c23e3> | seed | Definition of Emotional Disturbance
The Individuals with Disabilities Education Act (IDEA) defines emotional disturbance as follows:
“…a condition exhibiting one or more of the following characteristics over a long period of time and to a marked degree that adversely affects a child’s educational performance:
An inability to learn that cannot be explained by intellectual, sensory, or health factors.
An inability to build or maintain satisfactory interpersonal relationships with peers and teachers.
Inappropriate types of behavior or feelings under normal circumstances.
A general pervasive mood of unhappiness or depression.
A tendency to develop physical symptoms or fears associated with personal or school problems.”
As defined by IDEA, emotional disturbance includes schizophrenia but does not apply to children who are socially maladjusted, unless it is determined that they have an emotional disturbance.
As is evident in IDEA’s definition, emotional disturbances can affect an individual in areas beyond the emotional. Depending on the specific mental disorder involved, a person’s physical, social, or cognitive skills may also be affected. The National Alliance on Mental Illness (NAMI) puts this very well:
Mental illnesses are medical conditions that disrupt a person’s thinking, feeling, mood, ability to relate to others and daily functioning. Just as diabetes is a disorder of the pancreas, mental illnesses are medical conditions that often result in a diminished capacity for coping with the ordinary demands of life.
Some of the characteristics and behaviors seen in children who have an emotional disturbance include:
Hyperactivity (short attention span, impulsiveness);
Aggression or self-injurious behavior (acting out, fighting);
Withdrawal (not interacting socially with others, excessive fear or anxiety);
Immaturity (inappropriate crying, temper tantrums, poor coping skills); and
Learning difficulties (academically performing below grade level).
Children with the most serious emotional disturbances may exhibit distorted thinking, excessive anxiety, bizarre motor acts, and abnormal mood swings.
Many children who do not have emotional disturbance may display some of these same behaviors at various times during their development. However, when children have an emotional disturbance, these behaviors continue over long periods of time. Their behavior signals that they are not coping with their environment or peers.
Last Modified: 5/23/2013 2:16:53 PM |
<urn:uuid:d4130ffd-7d32-45eb-be4d-f7a3c0a55863> | seed | Sarcomas are soft-tissue neoplasms that can present themselves almost anywhere in the body. Some 70 tumor subtypes compose the sarcoma umbrella and each carries with it unique effects, treatments, and prognostic factors.
The word sarcoma is a slanted adaptation of the Greek word sarkoma, which means “fleshy growth”. These tumors account for about 0.7% of cancer cases in the United States, making them a relatively uncommon disease.
An angiosarcoma is a rare, malignant subtype of sarcoma that describes a wide array of neoplasms that originate in blood vessels and the linings of various blood-filled sites throughout the body. This sarcoma subtype is an aggressive cancer with a strong tendency to recur locally. Furthermore, this cancer often spreads quickly throughout the body, including metastasis in the lymphatic system. Prognosis is usually poor.
Angiosarcoma Symptoms and Features
The most common locations for angiosarcomas are the breasts, skin, deep tissue, and the liver. These tumors, however, have the ability to occur almost anywhere. Most cutaneous angiosarcomas (angiosarcomas of the skin) are found on the face and scalp.
It is estimated that 60% of all angriosarcomas are of the cutaneous variety. Another 25% of these growths are called soft-tissue angiosarcomas. 8% are angiosarcomas of the breast. Between 1 and 2% of all sarcomas are of the angiosarcoma subtype.
Learn more about the symptoms of angiosarcoma.
Angiosarcoma Common Risk Factor
- Chemical Exposure: Angiosarcomas can develop in the absence of an inciting cause, but certain high-risk materials have been shown to affect the presence of this cancer. These materials include, but are not limited to, vinyl chloride, thorium dioxide, and arsenic.
Angiosarcoma Common Symptoms
Physicians, when looking for an angiosarcoma, may consider the following symptoms and indicators of the disease:
- Skin Lesions
- Bone Pain
- Anemia: A disorder characterized by low levels of a molecule called hemoglobin in the red blood cells.
- A Growth: A lump or swelling located beneath or on the surface of the skin.
- Pain: Pains ranging from dull aches to stabbing sensations.
Little or nothing is often ascertained through blood work regarding the detection of angiosarcoma. To locate and determine the extent of the tumor’s growth, technologies such as magnetic resonance imaging (MRI), computed tomography (CT scan), radiography, and bone scanning are employed. An analysis of the results from these imaging technologies is the primary diagnostic tool for physicians looking for angiosarcomas.
Angiosarcomas develop so gradually that they are often well established by the time of diagnosis. Diseases such as this are defined by the term insidious. Furthermore, this sarcoma subtype does not respond well to most traditional angiosarcoma treatments such as chemotherapy, radiation therapy, steroid administration, and a variety of commonly employed drug therapies.
To amplify the complications associated with angiosarcoma, only 20 to 60 cases are diagnosed annually. Thus, the combination of aggressive growth, few treatment options, and extreme rarity makes angiosarcoma one of the deadliest cancers.
This cancer is rarely detected early in its development, but when early detection occurs, such cases may respond well to surgery, chemotherapy, and radiation therapy. Even so, most treatments of this cancer are not intended to be curative. Medications are often prescribed to reduce symptoms such as fatigue, anemia, and pains. Various surgeries are usually performed to promote a healthy appearance and a more comfortable day-to-day life for the patient.
Angiosarcomas typically carry with them a high death rate and short survival time. Due to the disease’s rarity, it is difficult to assess statistical findings and research, but studies indicate that most people survive for 15 to 24 months after the development of angiosarcoma. However, up to 33% of patients could survive for as many as 5 years. |
<urn:uuid:2aee1074-86a9-432a-a3b0-57ef9a001d80> | seed | LONDON, England, Wednesday September 19, 2012 – The results of a recent clinical trial of a vaccine against dengue fever have indicated that the mosquito-borne disease is unlikely to be eradicated in the Caribbean, or anywhere else, anytime soon.
In development by French drug manufacturer Sanofi SA, the world’s most advanced vaccine against dengue proved only 30 percent effective in a large clinical trial in Thailand. On the upside, researchers said it showed for the first time that a safe vaccine was possible.
Well below the 70 percent-plus efficacy researchers had anticipated at the start of the company-funded trial, the disappointing outcome was due to the vaccine’s failure to protect against one type of dengue virus, which turned out to be the most prevalent in Thailand at the time of the study.
Dengue fever, also known as “breakbone fever”, is a threat to nearly three billion people and is caused by four types of virus, none of which confers immunity from the others.
The outlook had originally been optimistic for the Thai trial, given that dengue belongs to the same virus class as yellow fever and Japanese encephalitis, both of which are controlled with highly effective existing vaccines.
It nevertheless appears that making a mixed dengue vaccine containing four different virus strains can produce uneven results, illustrating the complexity of a disease that scientists have been trying to combat for over 70 years.
Sanofi disclosed in July that the Thai dengue study showed efficacy against three of the four strains, without giving details. The full findings were published online last week in the The Lancet medical journal.
Jean Lang, Sanofi’s head of dengue vaccine development, said that, despite the disappointment, the Phase IIb study involving 4,002 Thai children was encouraging, given the protection provided against three out of four of the virus strains.
Efficacy was around 60 percent against dengue virus type 1 and 80-90 percent against types 3 and 4. A single dose of the vaccine proved roughly as good as three doses, moreover.
“This is a milestone, but we need to wait for the results of two large Phase III efficacy trials to have a better understanding of the vaccine,” Lang said.
Sanofi is conducting final-stage Phase III trials with 31,000 participants in Latin America and Asia, and attention will now focus on results for these ongoing Phase III trials, with any commercial launch in 2015 or later.
Other drug companies are also working on dengue vaccines but Sanofi’s product is several years ahead. The French group has already invested 350 million euros in a new French factory to make its vaccine.
An accompanying commentary on the study in The Lancet said it was possible that a vaccine against three out of four virus strains might still combat dengue effectively, since severe disease is caused by a second infection.
Dengue is spread by the bite of the Aedes aegypti mosquito, and in the past 50 years there has been a 30-fold jump in cases. The World Health Organisation (WHO) officially puts infections at 50-100 million a year, though many experts think this assessment from the 1990s is an underestimate.
Most patients survive dengue, but it is estimated to kill about 20,000 every year, many of them children. |
<urn:uuid:fbcfac35-3542-4a2d-838f-78cb4019a49f> | seed | Infections during pregnancy may have serious consequences for both mother and baby. Assessment of risk factors for infections informs planning of interventions and analysis of the impact of infections on health outcomes.
To describe risk factors for helminths, malaria and HIV in pregnant Ugandan women before intervention in a trial of de-worming in pregnancy.
The trial recruited 2,507 pregnant women between April 2003 and November 2005. Participants were interviewed and blood and stool samples obtained; location of residence at enrolment was mapped. Demographic, socioeconomic, behavioral and other risk factors were modelled using logistic regression.
There was a high prevalence of helminth, malaria and HIV infection, as previously reported. All helminths and malaria parasitemia were more common in younger women, and education was protective against every infection. Place of birth and/or tribe affected all helminths in a pattern consistent with the geographical distribution of helminth infections in Uganda. Four different geohelminths (hookworm, Trichuris, Ascaris and Trichostrongylus) showed a downwards trend in prevalence during the enrolment period. There was a negative association between hookworm and HIV, and between hookworm and low CD4 count among HIV-positive women. Locally, high prevalence of schistosomiasis and HIV occurred in lakeshore communities.
Interventions for helminths, malaria and HIV need to target young women both in and out of school. Antenatal interventions for malaria and HIV infection must continue to be promoted. Women originating from a high risk area for a helminth infection remain at high risk after migration to a lower-risk area, and vice versa, but overall, geohelminths seem to be becoming less common in this population. High risk populations, such as fishing communities, require directed effort against schistosomiasis and HIV infection.
Infections in pregnancy can cause miscarriage, stillbirth, maternal mortality, and low birth weight and have other long-term complications for mother and baby, although the full impact of many infections, particularly worm infections, is not yet fully understood. There is a high burden of infectious disease in many developing countries. In this analysis, we identified which factors put pregnant women in Entebbe, Uganda, at particular risk for worm infections, malaria, HIV, and, where possible, rarer infections including syphilis. The women in this study, and their children, will be followed up to determine the long-term effects of exposure of the fetus to these maternal infections on health during childhood. The findings of this baseline analysis will help in the interpretation of the long-term outcomes. The findings also highlight which groups are most at risk of each infection, and this may help in targeting interventions to prevent, treat, or mitigate the impact of infections in pregnancy. |
<urn:uuid:887f8951-50eb-4730-9822-bcb91d5f064a> | seed | April 29, 2005
The Perfect Practice Patient
The New Yorker's Annals of Medicine column this week contains an interesting overview on the use of the simluator to help medical school students and practicing physicians refine their skills.
At most schools, medicine is still taught largely as it has been for centuries, with students and young doctors serving as apprentices to veteran physicians. Training begins with textbook descriptions of cases and is followed, in the second or third year of medical school, by instruction at the patient’s bedside, an approach known as “See One, Do One, Teach One”: the student or intern observes the diagnosis and treatment of a particular disorder and is encouraged to take charge the next time a similar case occurs. . . .
However, the apprenticeship model is becoming increasingly difficult to sustain. As insurers reduce reimbursements to hospitals, senior doctors are under pressure to focus on revenue-generating work—treating sick people and conducting procedures—rather than on teaching. Moreover, in order to cut costs, operations and therapies that once took place over several days are now performed in a few hours, or in outpatient settings. As a result, students are spending less time with individual patients and have fewer opportunities to observe a case from diagnosis to resolution. Some life-threatening conditions, such as anaphylactic shock or a ruptured aortic aneurysm, occur infrequently enough that a trainee may become a licensed physician without encountering such disorders or mastering the skills to treat them. Health care may be unique among high-risk fields in that learning takes place largely on human beings.
Dr. David Gaba, an anesthesiologist who directs a simulation center at the Veterans Affairs Palo Alto Health Care System, and who teaches at the Stanford University School of Medicine, created one of the first patient simulators nearly twenty years ago, in an effort to change the way physicians are taught. Gaba estimates that fewer than half of the medical schools in the United States routinely use the devices today. (meti, a Florida company that is one of this country’s principal manufacturers of high-tech medical simulators, says that it has sold more than sixty to schools in the past eight years.) “You wouldn’t get on an airplane unless the pilot had been trained in a flight simulator and certified to use the new instruments on a jet,” Gaba told me. “Why would you place yourself in the hands of a doctor who hadn’t proven his competency and been certified on a simulator?”
These dummy patients are quite realistic and it makes sense that doctors should be practicing techniques and learning how to treat a variety of ailments on them rather than experimenting on the rest of us. Unfortunately as the article points out, the fake patients are very expensive. Perhaps medical malpractice insurance companies can be persuaded to purchase some of these simulators for medical schools to help increase quality of care and prevent malpractice. [bm]
April 29, 2005 | Permalink |
<urn:uuid:4987e278-d1cc-4852-82ae-43d80a71efa0> | seed | Neuropathic pain is pain coming from damaged nerves. It is different from pain messages carried along healthy nerves from damaged tissue (for example from a fall, a cut, or arthritic knee). Neuropathic pain is treated by different medicines than pain from damaged tissue. Medicines like paracetamol or ibuprofen are not effective in treating neuropathic pain, while medicines that are sometimes used to treat depression or epilepsy can be very effective in some people with neuropathic pain. Our knowledge about fibromyalgia is even less advanced, but fibromyalgia can respond to the same medicines as neuropathic pain.
Topiramate is a medicine used to treat epilepsy, and so it might be a useful medicine for neuropathic pain or fibromyalgia.
On 8 May 2013, we performed searches to look for clinical trials on the use of topiramate to treat neuropathic pain or fibromyalgia. We found four studies of reasonable quality that tested topiramate against placebo for a number of weeks. Almost all of the 1684 people in the studies had painful limbs because of damaged nerves caused by diabetes.
Topiramate did not help the pain and was no different from placebo except in causing more side-effects, which made many more people withdraw from the studies early. About 3 people in 10 withdrew because of side-effects with topiramate compared with 1 in 10 with placebo.
Topiramate has not been shown to work as a pain medicine in diabetic neuropathy.
Topiramate is without evidence of efficacy in diabetic neuropathic pain, the only neuropathic condition in which it has been adequately tested. The data we have includes the likelihood of major bias due to LOCF imputation, where adverse event withdrawals are much higher with active treatment than placebo control. Despite the strong potential for bias, no difference in efficacy between topiramate and placebo was apparent.
Topiramate is an antiepileptic drug with multiple possible mechanisms of action. Antiepileptic drugs are widely used to treat chronic neuropathic pain (pain due to nerve damage) and fibromyalgia, and many guidelines recommend them.
To assess the analgesic efficacy and associated adverse events of topiramate for chronic neuropathic pain and fibromyalgia in adults (aged 18 years and above).
On 8 May 2013, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, and EMBASE. We reviewed the bibliographies of all randomised trials identified and review articles, and also searched two clinical trial databases, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform, to identify additional published or unpublished data.
We included randomised controlled trials (RCTs) with double-blind assessment of participant outcomes following two weeks of treatment or longer (though the emphasis of the review was on studies of eight weeks or longer) that used a placebo or active comparator.
We extracted efficacy and adverse event data, and two study authors examined issues of study quality independently. We performed analysis using two tiers of evidence. The first tier used data where studies reported the outcome of at least 50% pain reduction from baseline, lasted at least eight weeks, had a parallel group design, included 200 or more participants in the comparison, and reported an intention-to-treat analysis. First tier studies did not use last-observation-carried-forward (LOCF) or other imputation methods for dropouts. The second tier used data that failed to meet this standard; second tier results were therefore subject to potential bias.
We included four studies with 1684 participants. Three parallel-group placebo comparisons were in painful diabetic neuropathy (1643 participants), and one cross-over study with diphenhydramine as an active placebo (41 participants) was in lumbar radiculopathy. Doses of topiramate were titrated up to 200 mg/day or 400 mg/day. All studies had one or more sources of potential major bias, as they either used LOCF imputation or were of small size.
No study provided first tier evidence for an efficacy outcome. There was no convincing evidence for efficacy of topiramate at 200 to 400 mg/day over placebo.
Eighty-two per cent of participants taking topiramate 200 to 400 mg/day experienced at least one adverse event, as did 71% with placebo, and the number needed to treat for an additional harmful effect (NNTH) was 8.6 (95% confidence interval (CI) 4.9 to 35). There was no difference in serious adverse events recorded (6.6% versus 7.5%). Adverse event withdrawals with 400 mg daily were much more common with topiramate (27%) than with placebo (8%), with an NNTH of 5.4 (95% CI 4.3 to 7.1). Lack of efficacy withdrawal was less frequent with topiramate (12%) than placebo (18%). Weight loss was a common event in most studies. No deaths attributable to treatment were reported. |
<urn:uuid:656b86c5-a061-4613-bf78-92dc534c02ac> | seed | Volume 13, Number 9—September 2007
Rickettsia monacensis and Human Disease, Spain
We identified Rickettsia monacensis as a cause of acute tickborne rickettsiosis in 2 humans. Its pathogenic role was assessed by culture and detection of the organism in patients’ blood samples. This finding increases the number of recognized human rickettsial pathogens and expands the known geographic distribution of Mediterranean spotted fever–like cases.
Tickborne rickettsioses are produced by spotted fever group (SFG) rickettsiae and cause an expanding spectrum of clinical signs. Rickettsia conorii is the etiologic agent of Mediterranean spotted fever (MSF) and is transmitted by Rhipicephalus sanguineus. Rickettsia helvetica, a widespread species, is carried by Ixodes ricinus (1). Recently, other SFG rickettsiae have been found in I. ricinus from Spain (2), Slovakia (3), and northeastern Italy (4), as well as in I. nipponensis from Japan (5). Subsequently, a new rickettsia species, R. monacensis, was isolated from I. ricinus from Germany (6) and detected in Hungary (7). The pathogenicity of this species is unknown. It constitutes a new rickettsial genotype and forms a separate cluster among the SFG rickettsiae (3), close to strain Cooleyi, which was isolated from I. scapularis in Texas (8). I. ricinus is well established in areas of northern Spain (9), where MSF-like cases are increasingly reported.
Our study aim was to identify the SFG rickettsial species involved in MSF-like rickettsioses in 2 patients in northern Spain. We report an association between R. monacensis and these rickettsioses.
Patient 1 was an 84-year-old man from La Rioja, who sought medical attention on June 19, 2003, 7 days after onset of fever (39.5ºC), general discomfort, headache, and joint pain. At the time of the physical examination, he had a nonpruritic, disseminated maculopapular rash, with no inoculation eschar, of the trunk and lower extremities, including palms and soles. Other than a slightly low platelet count (82,000/mm3), examination findings were within normal limits. MSF was diagnosed, and serum and defibrinated blood samples were taken before a course of oral doxycycline (100 mg/12 h for 10 d) was initiated. Three days later, fever and rash were gone without sequelae. Additional serial serum samples were taken during weeks 4, 13, and 26 after onset and reserved for serologic analysis (Table).
Patient 2 was a 59-year-old woman from Basque Country, who sought medical attention on September 20, 2003, 4 days after onset of fever (38ºC), headache, and an erythematous rash, with no inoculation eschar, at the site of a tick bite. The patient reported a history of tick bites, most recently 1 week before symptom onset. Blood cell counts and other blood chemistry values were normal. MSF was diagnosed, and oral doxycycline (100 mg/12 h for 10 d) was prescribed. Serial serum samples were taken the day of the visit and weeks 4 and 6 after onset and were reserved for serologic analysis (Table). Defibrinated blood was also taken 2 days after treatment was initiated. The patient recovered without sequelae.
DNA was extracted with the QIAGEN Tissue kit (IZASA S.A., Barcelona, Spain), and an ompA-nested PCR was designed. The first set of primers (Rr190.70p and Rr190.602n) have been described (10). Those used for the nested amplification were designed in this study: NompA-F (5′-AGC GAT AAT GCT GAG TAG TAG-3′) and NompA-R (5′-TAT ATT TCC TAA ACC TGT ATA A-3′) nucleotide positions 150–170 and 576–555, respectively, were numbered according to Regnery et al. (10). Amplification conditions were as described, except annealing temperature was 40ºC for the second PCR and AmpliTaq Gold DNA Polymerase (Applied Biosystems, Branchburg, NJ, USA) was used. The specificity of the method was tested against DNA obtained from Vero cells and Coxiella burnetii, and fragments of the expected sizes (532 and 427 bp) were obtained from different rickettsia species (data not shown). The amplicons obtained from blood samples were run in 1% low-melt agarose gels (Pronadisa, Barcelona, Spain), and the bands of interest were excised, purified with QIAquick Gel Extraction kit (IZASA S.A), and sequenced as described (9).
A phylogenetically informative fragment of 446 bp of gltA was also sequenced from samples by nested PCR with primers designed for this study: GLTA1F (5′-GAC GGT GAT AAA GGA ATC TTG-3′) and GLTA1R (5′-CAT TTC TTT CCA TTG TGC CAT C-3′) for the first run, and GLTA2F (5′-CTA CGA ACT TAC CGC TAT TAG-3′) and GLTA2R (5′-GAC CAA AAC CCA TTA ACC TAA AC-3′) for the second; nucleotide positions 279–299, 1011–989, 566–586, and 1298–1277, respectively, were numbered according to Regnery et al. (10). PCR conditions included annealing temperatures of 65ºC and 50ºC for the first and second runs, respectively. The rest of the parameters were identical to those used above, and samples were subjected to 35 cycles of denaturing (20 s at 95ºC), annealing (30 s), and extension (2 min at 60ºC), with an initial denaturing cycle of 9 min at 95ºC.
Blood samples from each patient were cultured by using shell vial technique (11). Giménez stain and PCR, performed after 7 days of incubation, confirmed the growth of a Rickettsia-like organism (strain Rp-Sp1) from patient 1. The sequences of ompA and gltA of this isolate (GenBank accession nos. DQ157778 and DQ517498, respectively) were identical to those obtained from the blood samples of each patient and to that of R. monacensis (6) (GenBank accession nos. AF201329 and DQ100163). The sequences generated in this study were subjected to phylogenetic analyses as described (9) and belonged to the same clade as R. monacensis and other related strains that have been detected in I. ricinus (3,4,12) (Figure).
In-house microimmunofluorescence assay (IFA) ( and references therein) that used R. monacensis, R. conorii, R. helvetica, R. akari, and R. australis as antigens was performed in serial serum samples from each patient (Table). The isolate Rp-Sp1 from patient 1 could not be used as antigen because of poor adaptation of this isolate to culture in Vero cell monolayers; R. monacensis slides for IFA were obtained from the Department of Entomology, University of Minnesota, Minneapolis, MN, USA. Seroconversion against the 5 rickettsia species was observed from patient 1’s second serum sample (day 30 after the onset). Patient 2’s first serum sample also had high titers against the 5 antigens. Although the reactivity against the 5 rickettsial antigens was similar, the titers observed were slightly higher against R. monacensis and R. helvetica, which are phylogenetically closer to each other than to the other species tested. However, because the serologic results may only loosely implicate a given rickettsia species, isolation of R. monacensis from patient 1 and its detection by PCR for both patients confirm it as the etiologic agent.
We describe a new, to our knowledge, rickettsia species that caused human disease. R. monacensis was the etiologic agent of MSF-like illness in northern Spain. Strain Rp-Sp1 was obtained from 1 patient. Because the sequences of ompA and gltA were identical to this rickettsia species and also amplified from blood samples of each patient studied, we conclude that this rickettsia is responsible for the symptoms observed in these patients. Therefore, R. monacensis joins the list of autochthonous rickettsia species (R. conorii , R. slovaca , R. typhi ) confirmed as human pathogens in Spain.
We were not able to study the vectors involved; however, each patient contracted the disease in areas where I. ricinus is the most prevalent tick species (9), and strains close to R. monacensis have been recently detected in I. ricinus in Spain (2,12). Thus, I. ricinus may eventually be shown to be the vector. Studies of R. monacensis incidence in autochthonous I. ricinus specimens are in progress to evaluate the risk of its transmission to humans.
Dr Jado is a microbiologist at the “Unidad de Alerta y Emergencias” and Laboratorio de Espiroquetas y Patógenos Especiales, Centro Nacional de Microbiología, Instituto de Salud Carlos. Her research interest is bacterial zoonoses, specifically tickborne pathogens.
We thank Ulrike Munderloh for providing R. monacensis slides for IFA.
Grant support was provided by Fondo de Investigación Sanitaria “Red Temática de Investigación Cooperativa EBATRAG (G03/057).”
- Parola P, Paddock CD, Raoult D. Tick-borne rickettsioses around the world: emerging diseases challenging old concepts. Clin Microbiol Rev. 2005;18:719–56.
- Márquez FJ, Muniain MA, Soriguer RC, Izquierdo G, Rodríguez-Bano J, Borobio MV. Genotypic identification of an undescribed spotted fever group rickettsia in Ixodes ricinus from southwestern Spain. Am J Trop Med Hyg. 1998;58:570–7.
- Sekeyova Z, Fournier PE, Rehacek J, Raoult D. Characterization of a new spotted fever group rickettsia detected in Ixodes ricinus (Acari: Ixodidae) collected in Slovakia. J Med Entomol. 2000;37:707–13.
- Beninati T, Lo N, Noda H, Esposito F, Rizzoli A, Favia G, First detection of spotted fever group rickettsiae in Ixodes ricinus from Italy. Emerg Infect Dis. 2002;8:983–6.
- Ishikura M, Ando S, Shinagawa Y, Matsuura K, Hasegawa S, Nakayama T, Phylogenetic analysis of spotted fever group rickettsiae based on gltA, 17-kDa, and rOmpA genes amplified by nested PCR from ticks in Japan. Microbiol Immunol. 2003;47:823–32.
- Simser JA, Palmer AT, Fingerle V, Wilske B, Kurtti TJ, Munderloh UG. Rickettsia monacensis sp. nov., a spotted fever group rickettsia, from ticks (Ixodes ricinus) collected in a European city park. Appl Environ Microbiol. 2002;68:4559–66.
- Sreter-Lancz Z, Sreter T, Szell Z, Egyed L. Molecular evidence of Rickettsia helvetica and R. monacensis infections in Ixodes ricinus from Hungary. Ann Trop Med Parasitol. 2005;99:325–30.
- Billings AN, Teltow GJ, Weaver SC, Walker DH. Molecular characterization of a novel Rickettsia species from Ixodes scapularis in Texas. Emerg Infect Dis. 1998;4:305–9.
- Escudero R, Barral M, Pérez A, Vitutia MM, García-Pérez AL, Jiménez S, Molecular and pathogenic characterizacion of Borrelia burgdorferi sensu lato isolates from Spain. J Clin Microbiol. 2000;38:4026–33.
- Regnery RL, Spruill CL, Plikaytis BD. Genotypic identification of rickettsiae and estimation of intraspecies sequence divergence for portions of two rickettsial genes. J Bacteriol. 1991;173:1576–89.
- La Scola B, Raoult D. Diagnosis of Mediterranean spotted fever by cultivation of Rickettsia conorii from blood and skin samples using the centrifugation-shell vial technique and by detection of R. conorii in circulating endothelial cells: a 6-year follow-up. J Clin Microbiol. 1996;34:2722–7.
- Fernández-Soto P, Pérez-Sánchez R, Encinas-Grandes A, Sanz RA. Detection and identification of Rickettsia helvetica and Rickettsia sp. IRS3/IRS4 in Ixodes ricinus ticks found on humans in Spain. Eur J Clin Microbiol Infect Dis. 2004;23:648–9.
- Bernabeu-Wittel M, Segura-Porta F. Rickettsiosis. Enferm Infecc Microbiol Clin. 2005;23:163–72.
- Oteo JA, Ibarra V, Blanco JR, Martínez de Artola V, Márquez FJ, Portillo A, Dermacentor-borne necrosis erythema and lymphadenopathy: clinical and epidemiological features of a new tick-borne disease. Clin Microbiol Infect. 2004;10:327–31.
- Hernández-Cabrera M, Ángel-Moreno A, Santana E, Bolaños M, Frances A, Martín-Sánchez MS, Murine typhus with renal involvement in Canary Islands, Spain. Emerg Infect Dis. 2004;10:740–3.
Suggested citation for this article: Jado I, Oteo JA, Aldámiz M, Gil H, Escudero R, Ibarra V, et al. Rickettsia monacensis and human disease, Spain. Emerg Infect Dis [serial on the Internet]. 2007 Sep [date cited]. Available from http://wwwnc.cdc.gov/eid/article/13/9/06-0186
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<urn:uuid:09b6b53c-7a6e-4fe2-806a-4d9fce94049a> | seed | Aug. 10, 2009 Manuela Baccarini, Professor for Cell Signalling at the Centre of Molecular Biology of the University of Vienna (Max F. Perutz Laboratories) and colleagues reveal the function of a protein in the Ras signalling pathway. Their findings provide the basis for research on novel therapeutic strategies in Ras-induced skin cancers, e.g. melanoma. The results of her work are published in the scientific journal Cancer Cell.
Ras is a protein which is a master regulator of several signalling cascades in cells, and has been demonstrated to be a proto-oncogene. If the protein is mutated or misregulated by outside influences, it contributes to the development of skin cancers such as melanoma.
Skin cancer develops from a progenitor skin cell population that expands unrestrictedly (proliferation) and does not migrate from the deeper skin layers (stratum basale) to the surface (stratum corneum) to differentiate into specialized skin cells or keratinocytes. In addition, compared to normal cells, tumour cells have also lost the ability to react to "cell suicide signals" (apoptosis).
Cell differentiation decisive for melanoma development
Up until now it was believed that the crucial process for skin cancer development is the unrestricted cell proliferation of the progenitor cells. Baccarini and colleagues now show in a mouse model that the Ras signalling pathway is coupled to the Raf-1 protein. Unexpectedly, the Raf-1 protein plays a key role in the differentiation process of the progenitor skin cells and not in the proliferation as previously assumed. Raf-1 ablation induced total regression of the epidermal tumours in mice. Mice without epidermal Raf-1 did not develop skin cancer, even though the Ras pathway was active.
Enzyme complex allows novel therapeutic strategies
The disruption of the normal pathway from progenitor cell to keratinocyte allows for the possibility of skin cancer development, as cancers (eg. melanoma) frequently arise from these progenitor cells. "We showed that Raf-1 builds an enzymatic complex with the protein Rok. This complex inhibits the differentiation to a skin cell and the way is clear for skin cancer development", Manuela Baccarini explains. She also identifies novel therapeutic avenues: "In the treatment of leukaemia substances are administered which stimulate cells to differentiate, combined with chemotherapy."
This combined therapy could be used for skin cancer treatment as well, if a substance is discovered that destroys the Raf-Rok complex and therefore enables differentiation. "The search for such substances up to the clinical application is a long road", Baccarini cautions. But with the discovery of this basic mechanism of skin cancer development Manuela Baccarini and colleagues provide the basis for research on novel therapeutic strategies.
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<urn:uuid:7fdc3233-01be-40dd-b7f6-e44b73cd6996> | seed | SALT LAKE CITY Using advanced computer simulations, University of Utah College of Pharmacy researchers have produced moving images of a protein complex that is an important target for anti-cancer drugs. This advancement has significant implications for discovering new therapies that could attack cancer without damaging the DNA of healthy cells, according to an article published July 31, 2012 in the Proceedings of the National Academy of Sciences.
The researchers used high-performance computing technology to demonstrate that a protein complex called LSD1/CoREST undergoes major changes in shape, which are regulated by binding to a DNA-packaging protein known as histone H3. LSD1 gene expression is increased in many cancers and insight into the changes in the LSD1/CoREST complex may help to accelerate development of epigenetic drugs that reprogram cancer cells to behave more normally.
Epigenetics is the study of changes in gene expression that are not caused by alterations in the DNA itself. Instead, these changes are caused by chemical modifications that switch parts of the genome on and off to regulate gene activity. These chemical modifications occur within the epigenome, a layer of chemical labels that covers the genome, and help to determine whether specific genes are active or inactive. Epigenetic drug discovery is based on the knowledge that the epigenome is flexible and could potentially be altered by therapeutic drugs.
Lysine-specific demethylase-1 (LSD1)/CoREST is a protein complex involved in epigenetic changes. Recent studies have shown that LSD1-CoREST is a binding partner for various proteins involved in regulating genes and modifying chromatin, the combination of DNA and DNA-packaging proteins called histones that make up the nucleus of a cell. Previous research also revealed that LSD1-CoREST binds to histone H3.
"In our earlier work, we discovered that LSD1/CoREST functions as a tiny clamp that can reversi
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University of Utah Health Sciences |
<urn:uuid:e984af0d-636f-44c9-8980-2f74105f1111> | seed | CardioBuzz is a blog by Todd Neale for readers with an interest in cardiology.
In a commentary in BMJ, Aseem Malhotra, MBChB, an interventional specialist registrar from Croydon University Hospital in London, argues that a focus on saturated fat as a major player in heart disease has been misguided and potentially harmful.
"Scientists universally accept that trans fats -- found in many fast foods, bakery products, and margarines -- increase the risk of cardiovascular disease through inflammatory processes," he wrote. "But 'saturated fat' is another story."
A major problem, Malhotra said, is that after studies suggested that high levels of cholesterol and saturated fat were associated with increased cardiovascular risk the food industry started replacing saturated fat with sugar (to compensate for loss of taste).
"The scientific evidence is mounting that sugar is a possible independent risk factor for the metabolic syndrome ...," he wrote.
"It is time to bust the myth of the role of saturated fat in heart disease and wind back the harms of dietary advice that has contributed to obesity," he concluded.
Here's a sampling of the reactions from leaders in nutrition and prevention who were contacted by MedPage Today (edited for length and clarity).
Walter Willett, MD, DrPH, Chair of the Department of Nutrition at the Harvard School of Public Health
For many years, saturated fat was deemed by many to be the major cause of cardiovascular disease (CVD). What we have learned is that it is part of the picture, although far from the whole picture. If compared with the typical carbohydrate in the U.S. diet, saturated fat has almost no effect on the LDL/HDL ratio or risk of heart disease. However, if compared with polyunsaturated fat, and probably monounsaturated fat in vegetable oils, it has an adverse effect. Thus, the advice in the late 1960s and 1970s to replace saturated fat with vegetable oils was almost certainly beneficial and contributed much to the large reduction in cardiovascular mortality. Unfortunately, with almost no evidence, in the 1980s the advice shifted to replacing saturated fat and total fat with carbohydrates, which was not helpful and probably harmful to many. We have started to recover from this, but it is taking a long time.
Malhotra is correct that a Mediterranean-type diet focused on the type of fat and that includes many fruits and vegetables, whole grains, nuts, legumes, and low amounts of red meat will be better (and it will be low in saturated fat, but not because that is the focus). Where the commentary goes too far is that red meat or dairy are not a problem; in an optimal diet they will be low because they will be mainly replaced by nuts, legumes, fish, and some poultry.
Scott Grundy, MD, PhD, Director of the Center for Human Nutrition at UT Southwestern Medical Center
The best evidence that saturated fats do raise cholesterol levels and contribute to coronary heart disease comes from Finland. Thirty years ago, Finnish people consumed diets very high in saturated fats. They also had very high cholesterol levels and high rates of heart disease. Through public health measures, intakes of saturated fats declined and so did coronary heart disease. Many other metabolic studies show that saturated fats raise cholesterol levels, and many epidemiological studies show that for every 1% rise in cholesterol there is a corresponding 1% to 2% rise in heart risk. Since saturated fats definitely raise cholesterol levels, it can be deduced that there is a corresponding increase in risk. Finally, a few smaller scale clinical trials show that people given high saturated fats have higher heart attack rates than those getting unsaturated fats.
David Katz, MD, MPH, Director of the Yale University Prevention Research Center
My opinion in general is that the current effort to exonerate saturated fat is guilty of all the same over-generalizations and misinterpretations as the effort to vilify saturated fat. Consider that a diet high in saturated fat was, of necessity, always proportionately lower in "other things" -- such as unsaturated fat, vegetables, fruits, etc. People who eat a lot of meat eat fewer beans and lentils. The active ingredient in a "bad diet" that happened to be high in saturated fat may always have been the "bad diet," with high saturated fat just one of its many liabilities. See, for instance, this quote below lifted directly from the commentary:
"In the past 30 years in the U.S. the proportion of energy from consumed fat has fallen from 40% to 30% (although absolute fat consumption has remained the same), yet obesity has rocketed."
The author uses this to support his argument that saturated fat is not harmful: we've cut fat and still gotten fatter. But he seems to ignore the far more important implication of his own statement: if fat intake has fallen as a percentage of calories, but absolute fat intake has remained constant, it means, ipso facto, that calorie intake has gone up! And yet, the author argues against the importance of calories to weight. This is, in fact, the very problem: we did not cut our fat intake. We just increased our calorie intake, adding lots of sugar and starches. The message to reduce saturated fat intake was, I believe, a message intended to mean: eat less cream, eat more spinach. It was perverted into: eat Snackwell cookies. We have modern epidemiology to show for it.
C. Noel Bairey Merz, MD, Director of the Preventive and Rehabilitative Cardiac Center at Cedars-Sinai Medical Center
Food is complex but it is clear that a Western diet that is high in animal protein, saturated fat, dietary cholesterol, oxidative stress (chips, fries) and low in polyunsaturated fatty acids (nuts, legumes, fish), fiber, and B vitamins (fruits and vegetables) is linked with higher rates of cardiovascular disease. Ancel Keys demonstrated long ago that saturated fat and dietary cholesterol raise serum cholesterol levels, but it is more complex than just saturated fat. Saturated fat and cholesterol were what could be identified at the time. We have moved on, but the U.K. has not.
Contemporary U.S. guidelines moved away from saturated fat and dietary cholesterol 10 years ago and now recommend a Mediterranean pattern of diet. History shows this is also what Ancel Keys proposed. In addition to U.S. studies, this is also supported by the most recent Spanish PriMed study that the author cites but he conveniently skipped over the part about shifting from animal (meat) to vegetable (legumes) protein and monounsaturated fat (olive oil) rather than butter and lard (saturated fat and dietary cholesterol).
The dietary change embraced by the U.S. in the 1960s (reducing butter and lard, whole milk, bacon, eggs, red meat) resulted in a population fall in total cholesterol in NHANES from approximately 220 to 210 mg/dL, which was accompanied by Ancel Keys' predicted percent reduction in CVD, falling right on the line. Rates have now fallen even further with the widespread use of statins lowering of serum cholesterol. Small changes in large populations make a difference for society that is not always measurable at the individual level. So it had an impact. The reverse is playing out in developing countries: China has dramatically increased their animal consumption as they have become prosperous and CVD rates are concurrently dramatically rising.
Michael Blaha, MD, MPH, Director of Clinical Research at the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease
Saturated fat, as a whole, probably plays a modest role in determining cardiovascular risk. However, it is probably inappropriate to lump all saturated fats together. Some saturated fats (like coconut oil and palm oil), may be, in fact, healthy. Indeed, it is pretty clear that dairy products consumed in moderation are probably healthy. Other sources of saturated fat, like those in red meat, may be modestly atherogenic. But this is hard to disentangle from other unhealthy aspects of processed red meat, including preservatives and the nitrate byproducts of high-temperature cooking.
I think it is pretty clear that the emphasis on reducing fat intake has led to increased intake of carbohydrates. Unfortunately, for the most part, this has been in the form of highly processed simple carbohydrates that drive the blood sugar up and tend to induce insulin resistance. There is little doubt that diet shifts in the last 20 to 30 years have directly contributed to the current epidemic of obesity, metabolic syndrome, and diabetes.
The message about what to eat needs to be more nuanced. It is probably inappropriate to single out a single macronutrient as harmful. The message should be to eat more fresh foods and less pre-packaged and pre-prepared foods.
I disagree with the statement in the article that the "government's obsession" with total cholesterol has led to overmedication of millions of people with statins. Statins have many beneficial effects independent of blood cholesterol levels, and current guidelines appropriately stress giving these medications to people at high cardiovascular risk, not exclusively on the basis of cholesterol levels.
Carl Lavie, MD, Medical Director of Cardiac Rehabilitation and Prevention at the John Ochsner Heart and Vascular Institute
It is true that replacing saturated fats with omega-6 fatty acids and carbohydrates is associated with potential problems, as there are concerns about linoleic acid, the main fatty acid in polyunsaturated fatty acids, which were raised by Scott Grundy almost 30 years ago. Also, in a society where energy expenditure -- including household management and occupational physical activity -- has markedly fallen during the past 5 decades, coupled with failure to make up for this with increased leisure-time physical activity, high-carbohydrate diets may be increasing insulin resistance and many of its consequences (whereas with high physical activity, eating sugars and complex carbohydrates would not be so detrimental). Ideally, without very high levels of physical activity, many would be better off with lower carbohydrate intakes, and higher fat intake -- probably of omega-3 fatty acids (fish oils) and omega-9 fatty acids (monounsaturated fats such as oleic acid or olive oil) -- would be ideal. But even so, saturated fats may be better than super high levels of carbohydrates. Saturated fats and cholesterol are safer than the trans fats.
Nevertheless, Malhotra says several things in his editorial that would be hard to defend. Statins have not been demonstrated to reduce short-term mortality in the primary prevention trials, where mortality is low in the control groups. Demonstrating mortality reductions would require studying higher-risk populations or following a low-risk population for much longer periods of time. Several of the primary prevention studies were stopped early (e.g., the ASCOT-LIPID trial in mild hypertensives), whereas projecting the mortality lines out a few more years likely would show a mortality benefit, and the CARDS trial (primary prevention in diabetes) almost had statistically significant mortality benefits in fewer than 3,000 patients followed for less than 4 years. Patients in both trials received only the very low dose of atorvastatin, 10 mg.
Finally, I favor a Mediterranean diet, but his statement that this has more benefits than statins is unfounded. The recent high-profile NEJM paper's results were all based on a relatively few number of strokes reduced with this diet, with no trends even for reducing coronary heart disease or total mortality. On the other hand, the statin trials in secondary prevention have reduced stroke, coronary heart disease, and total mortality, and the primary prevention statin trials have reduced coronary heart disease and stroke and were not powered for mortality. |
<urn:uuid:9ce86848-24cc-42e9-af40-2734ced91232> | seed | Rotavirus, predominantly of group A, is a major cause of severe diarrhoea worldwide, with the greatest burden falling on young children living in less-developed countries. Vaccines directed against this virus have shown promise in recent trials, and are undergoing effectiveness evaluation in sub-Saharan Africa. In this region limited childhood data are available on the incidence and clinical characteristics of severe group A rotavirus disease. Advocacy for vaccine intervention and interpretation of effectiveness following implementation will benefit from accurate base-line estimates of the incidence and severity of rotavirus paediatric admissions in relevant populations. The study objective was to accurately define the incidence and severity of group A rotavirus disease in a resource-poor setting necessary to make informed decisions on the need for vaccine prevention.
Methods and Findings
Between 2002 and 2004 we conducted prospective surveillance for group A rotavirus infection at Kilifi District Hospital in coastal Kenya. Children < 13 y of age were eligible as “cases” if admitted with diarrhoea, and “controls” if admitted without diarrhoea. We calculated the incidence of hospital admission with group A rotavirus using data from a demographic surveillance study of 220,000 people in Kilifi District. Of 15,347 childhood admissions 3,296 (22%) had diarrhoea, 2,039 were tested for group A rotavirus antigen and, of these, 588 (29%) were positive. 372 (63%) rotavirus-positive cases were infants. Of 620 controls 19 (3.1%, 95% confidence interval [CI] 1.9–4.7) were rotavirus positive. The annual incidence (per 100,000 children) of rotavirus-positive admissions was 1,431 (95% CI 1,275–1,600) in infants and 478 (437–521) in under-5-y-olds, and highest proximal to the hospital. Compared to children with rotavirus-negative diarrhoea, rotavirus-positive cases were less likely to have coexisting illnesses and more likely to have acidosis (46% versus 17%) and severe electrolyte imbalance except hyponatraemia. In-hospital case fatality was 2% among rotavirus-positive and 9% among rotavirus-negative children.
In Kilifi > 2% of children are admitted to hospital with group A rotavirus diarrhoea in the first 5 y of life. This translates into over 28,000 vaccine-preventable hospitalisations per year across Kenya, and is likely to be a considerable underestimate. Group A rotavirus diarrhoea is associated with acute life-threatening metabolic derangement in otherwise healthy children. Although mortality is low in this clinical research setting this may not be generally true in African hospitals lacking rapid and appropriate management.
Citation: Nokes DJ, Abwao J, Pamba A, Peenze I, Dewar J, Maghenda JK, et al. (2008) Incidence and Clinical Characteristics of Group A Rotavirus Infections among Children Admitted to Hospital in Kilifi, Kenya. PLoS Med 5(7): e153. doi:10.1371/journal.pmed.0050153
Academic Editor: Kim Mulholland, Centre for International Child Health, Australia
Received: April 30, 2007; Accepted: June 5, 2008; Published: July 22, 2008
Copyright: © 2008 Nokes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: Support was provided by The Wellcome Trust (061584, 076278), the Kenya Medical Research Institute and the MRC Diarrhoeal Pathogens Research Unit, South Africa. At an institutional level the funders had no role in study design, data collection and analysis, or preparation of this manuscript. As for all studies undertaken within KEMRI, the manuscript was reviewed by their publications committee prior to providing permission to publish. No other funder played a role in the decision to publish this manuscript.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: CI, confidence interval; DSS, demographic surveillance system; GARV, group A rotavirus; IQR, interquartile range; KDH, Kilifi District Hospital; MUAC, mid-upper arm circumference; OR, odds ratio; WHO, World Health Organization
Rotavirus is a leading global cause of diarrhea in babies and young children. Indeed, most children become infected at least once with this virus before their fifth birthday. Rotavirus is usually spread by children or their caregivers failing to wash their hands properly after going to the toilet and then contaminating food or drink. The symptoms of rotavirus infection—diarrhea, vomiting, and fever—are usually mild, but if the diarrhea is severe it can quickly lead to dehydration. Mild to moderate dehydration can be treated at home by providing the patient with plenty of fluids or with a special rehydration drink that replaces lost water and salts. However, for infants or toddlers who become severely dehydrated, rehydration with intravenous fluids (fluids injected directly into a vein) in hospital may be essential. Unfortunately, in developing countries in sub-Saharan Africa and elsewhere, this treatment is not widely available and every year more than half a million young children die from rotavirus infections.
Why Was This Study Done?
Two rotavirus vaccines that could reduce this burden of disease are currently undergoing clinical trials to determine their effectiveness in sub-Saharan Africa. However, very little is known about the incidence of severe rotavirus infections among children living in this region (that is, how many children develop severe disease every year) or about the clinical characteristics of the disease here. Public-health officials need this baseline information before they can make informed decisions about the mass introduction of rotavirus vaccination and to help them judge whether the intervention has been successful if it is introduced. In this study, the researchers examine the incidence and clinical characteristics of rotavirus infections (specifically, group A rotavirus [GARV] infections; there are several different rotaviruses but GARV causes most human infections) among children admitted to the district hospital in Kilifi, Kenya.
What Did the Researchers Do and Find?
During the 3-year study, more than 15,000 children under the age of 13 years were admitted to Kilifi District Hospital, a little under a quarter of whom had severe diarrhea. Nearly a third of the patients admitted with diarrhea who were tested had a GARV-specific protein in their stools (faeces); by contrast, only three in 100 children admitted without diarrhea showed any evidence of GARV infection. Two-thirds of the GARV-positive children were infants (under 1 year old). Using these figures and health surveillance data (records of births, deaths, and causes of death) collected in the area around the hospital, the researchers calculated that the annual incidence (per 100,000 children) of GARV-positive hospital admissions in the region was 1,431 for infants and 478 for children under age 5 years. Children with GARV-positive diarrhea were less likely to have other illnesses (for example, malnutrition) than those admitted with GARV-negative diarrhea, the researchers report, but were more likely to have life-threatening complications such as severe dehydration and salt imbalances in their blood. However, despite being more ill on admission, only 1 in 50 children with GARV-positive diarrhea died, compared to nearly 1 in 10 of the children with GARV-negative diarrhea; the GARV-positive children also left hospital quicker than those who were GARV-negative.
What Do These Findings Mean?
These findings indicate that severe GARV-positive diarrhea is a major cause of hospital admission among otherwise healthy young children in the Kilifi region of Kenya. By the time they are 5 years old, the researchers estimate that 1 in 50 of the children living in this region will have been admitted to hospital with severe GARV-positive diarrhea. Because rotavirus vaccines prevent virtually all severe rotavirus-associated disease (at least in developed countries where their effectiveness has been extensively tested), the researchers estimate that vaccination might prevent more than 28,000 hospitalizations annually across Kenya; however, this prediction assumes that it is valid to extrapolate from the data obtained from this one district hospital to the entire country.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050153.
- The US Centers for Disease Control and Prevention provides information about rotavirus infections, surveillance, and vaccination (in English and Spanish)
- The UK National Health Service Direct health encyclopedia provides information on rotavirus infections
- MedlinePlus also provides links to information on rotavirus (in English and Spanish)
- The African Rotavirus Surveillance Network is working to improve knowledge about rotavirus infections in Africa
- The Rotavirus Vaccine Program aims to reduce child illness and death from diarrhea by increasing the availability of rotavirus vaccines in developing countries (in English and Spanish)
- PATH, a nonprofit international organization that aims to create sustainable, culturally relevant solutions to global health problems, also provides detailed information on rotavirus surveillance and disease burden
Rotavirus is a major cause of severe diarrhoea worldwide causing in excess of 2 million hospitalisations per annum in under-5-y-old children , and group A rotavirus (GARV) is responsible for the vast majority of this disease . In terms of both morbidity and mortality, the greatest burden of GARV diarrhoea falls on young children living in less-developed countries [1,3], with Africa only second behind the Indian subcontinent in suffering the major disease impact . Two vaccines directed against this virus have been shown to be safe and highly effective [4,5], and trials of effectiveness are now in progress in sub-Saharan Africa. Evidence-based decisions regarding the wide-scale use of rotavirus vaccine intervention will benefit from accurate baseline estimates of the incidence and clinical characteristics of GARV in representative target populations [6,7].
Considerable effort has been expended in defining the burden of GARV-associated diarrhoeal disease burden in Africa. A recent review of data from 14 countries within the region reported a median prevalence of GARV in children admitted to hospitals with diarrhoea of 24% (range 13%–55%), 81% in children < 12 mo of age . In Kenya, GARV has been identified in 14%–39% of hospital diarrhoea cases [9–11]. More recently rotavirus surveillance has intensified through the support of the African Rotavirus Network and Rotavirus Vaccine Program . Nevertheless, there is a remarkable paucity of data on GARV incidence where the population from which the patients arise is demographically well defined. Furthermore, the clinical spectrum of GARV presentations is not well characterised. Accurate incidence estimation and clear case definitions are vital components for the evaluation of vaccine trial planning and programme evaluation. The objectives of this study were to define these components among paediatric inpatients in Kilifi.
Study Location and Population
The study was conducted at Kilifi District Hospital (KDH) in a rural area on the coast of Kenya. The population of Kilifi District are predominantly subsistence farmers of the Mgiriama tribe. Malaria transmission occurs in this area throughout the year, with peaks in November–January and May–August following seasonal rains. The paediatric wards at KDH include a 36-bed general ward and a six-bed high-dependency unit, which together admit over 5,000 children each year. A standardized clinical history, examination, and routine set of investigations (haematology, malaria parasite microscopy, and blood culture) are conducted on all admitted children [14–17] and the data entered directly into a computer database. Further investigations, including blood gas and biochemical analysis, are undertaken at the discretion of the admitting clinician and dependent on the needs of research studies in progress.
Since 2000 a demographic surveillance system (DSS) has followed a population of approximately 220,000 individuals residing in the area close to KDH . The DSS area encompasses 891 km2 and includes 15 administrative locations, which are further divided into 40 sublocations (Figure 1). This area included the residences of 80% of children admitted to KDH in the period 1998–2000. Every household was mapped and censused in 2000–2001 and was re-enumerated at subsequent visits; in total there have been ten enumeration rounds to-date, six occurring during the present 3 y study. A resident was defined as an individual who lives (sleeps more than 50% of nights) in the identified homestead or who intends to live there for a period of ≥ 3 mo and has already spent at least one night there. Births, deaths, and in- and out-migration events are recorded at re-enumeration visits; births and deaths among children are also recorded at the maternity department, vaccine clinic, and wards of KDH. All sources of demographic data are uploaded within 48 h to an integrated database system. From 16 April 2002 we have attempted to match each child admitted to KDH paediatric ward to the register of DSS residents to create accurate correspondence between numerator and denominator data for incidence estimates.
Sublocation data was pooled with nearest neighbour data where diarrhoea admissions in children under 5 y was less than 20 cases over the period of surveillance. (Using DSS data from Figure 2 of reference .)
Percentages within a box refer to the proportion sampled from the preceding box, except where describing the breakdown of reasons why stools were not collected (entitled “No stool”). “Time limit” indicates children who ceased to be eligible because they failed to provide a stool sample within 24 hours of admission. Absence of laboratory results for stool samples collected (*) was due to insufficient sample or mismatch of laboratory and admission numbers. In total 1,257 children with diarrhoea were not tested (NT) for GARV.
All children aged < 13 y admitted to the wards of KDH with a history of diarrhoea between 01 January 2002 and 31 December 2004 were eligible for inclusion in the study. These children are termed “cases.” Diarrhoea was defined as passing three or more loose stools during the preceding 24 h. To estimate the prevalence of GARV infection in the absence of diarrhoeal disease we studied a group of children who were admitted to the ward but who did not have a history of diarrhoea; these patients are termed “controls” in the study. Controls were contemporaneous to cases, randomly selected in a ratio of one control to each three cases of diarrhoea, with frequency matching to diarrhoea cases by age class. Stool samples were collected as soon as possible after completion of the recruitment process. To prevent possible confusion from nosocomial transmission, diarrhoea cases and nondiarrhoea controls became ineligible for recruitment 24 h after admission.
HIV diagnostic counselling and testing were not established in the wards at the time of this study and approval was not sought to determine the HIV status of the study patients. Written informed consent was obtained from the parent or caretaker of each participant. Ethical approval was granted for the study by the Kenyan National Research Ethical Committee and by the Coventry Research Ethics Committee, UK.
Stool samples were stored at −80 °C until shipment on dry ice for screening at the MRC Diarrhoeal Pathogens Research Unit, South Africa. GARV antigen testing was conducted using an enzyme immunoassay (IDEIA Rotavirus, DakoCytomation) according to the manufacturers instructions. GARV-positive samples from controls were tested for viral genome pattern by PAGE as described previously .
Analyses were performed by use of STATA v8.2 (StataCorp). Incidence was defined as the number, among residents, of cases per 100,000 person-years of observation within age and location strata, with Poisson-based 95% confidence intervals (CIs). Person-years of observation were defined as the midstudy resident population multiplied by the number of years of linked surveillance (2.71 y, i.e., 16 April 2002 to 31 December 2004). The resident population of the DSS at the midpoint of the study (24 August 2003) was interpolated from the linear equation determined by regressing population size (log10) for all ten enumeration rounds against the mid-date of each round. The midstudy population size for a sublocation was estimated as the midpoint resident population weighted by the fraction of individuals within that sublocation at the enumeration round with mid-date 30 May 2003. A sublocation was defined as near to the district hospital if part of its boundary fell within a circle of 5 km radius with KDH at its centre. The population of resident under-5-y-olds within this area represented 42% of the total in the DSS, and accounted for 43% of all resident diarrhoea admissions. Among patients with diarrhoea we examined the association between rotavirus infection and a range of clinical signs and symptoms, and coexisting illnesses. We defined severe malnutrition using a combination of mid-upper arm circumference (MUAC), visible severe wasting, and bipedal oedema . The diagnosis of severe pneumonia, very severe pneumonia, and shock followed modified WHO definitions [21,22]. Further categorisations on the basis of clinical and laboratory findings were as described previously [23,24]. Proportions were compared using the Fisher exact test (two-tailed) with exact 95% CIs and equality of distributions evaluated using the Wilcoxon rank-sum test. Adjusted odds ratios (ORs) were determined using logistic regression.
Over the 3-y period 15,347 children aged < 13 y of age were admitted to KDH. There were 3,296 diarrhoea cases with a median age of 13 mo (interquartile range [IQR] 8–23 mo); 1,397 (42%) were female. For 35% (1,145) of cases a stool sample was not collected, for the reasons detailed in Figure 2, with the most important being a failure to provide a sample within the 24 h time limit postadmission. Relative to those who did provide a stool specimen, those who did not were more likely to be admitted directly to the high-dependency ward (15% versus 4%, p < 0.001) and to die before discharge (13% versus 7%, p < 0.001). One hundred twelve diarrhoea cases who provided a stool sample had no GARV test results. An analysis of the possible bias upon rotavirus incidence and severity characteristics from omission of the 1,257 eligible cases who were not GARV tested, provided evidence that the influence was not substantial (see Table S1 and Text S1). There were 12,051 patients admitted without diarrhoea, of whom 1,067 were selected as controls. The median age of the control group was 11 mo (IQR 4–22 mo); 455 (43%) were female. Reasons for failure to collect a stool sample from controls were in similar proportions to cases (Figure 2). The severity differential in sampled and nonsampled controls was also similar to that of cases. Among children tested for GARV antigen in the diarrhoea and control groups, the age (median 12.5 versus 12.2 mo, p = 0.219) and sex (proportion female 43% versus 42%, p = 0.926) distributions were very similar.
GARV-Associated Diarrhoea: Seasonality and Age Distribution
Twenty-nine percent (588/2,039) of stool samples tested positive for GARV antigen (Table 1). This proportion did not vary significantly by calendar year (p = 0.686) or by sex (p = 0.199). Variation in the monthly GARV-positive cases mirrored approximately the pattern of diarrhoea admissions but had no clear seasonal pattern or obvious association with weather indicators (see Figure S1). Of all diarrhoea cases 83% were aged 3–17 mo (Table 2) and the proportion of cases GARV positive was higher in this age group (37%) than among other children (14%). While 19% of cases under 3 mo old were GARV positive, only 3% of all GARV positives were found in this age group.
The Incidence (Per 100,000 Per Year) of Severe Diarrhoea and GARV-Positive Severe Diarrhoea Estimated from Surveillance of Admissions to Kilifi District Hospital, Kenya 2002–2004
Age Distribution of Paediatric Cases of Diarrhoea Tested for GARV and Those Found GARV-Positive from Admissions to KDH, Kenya between 01 January 2002 and 31 December 2004
GARV in Children Admitted without Diarrhoea
Of the 620 control specimens, 19 (3.1%; 95% CI 1.9%–4.7%) tested positive for GARV. This proportion did not vary by calendar year or by sex. PAGE analysis identified GARV RNA in 14 (74%) of the 19 positives. A review of the clinical records confirmed that none of the GARV-positive controls gave a history of diarrhoea in the week prior to admission.
The Community Burden of GARV-Associated Diarrhoea
The incidence rates for admission to KDH with diarrhoea and with GARV-associated diarrhoea are shown in Table 1. We assume to be negligible the proportion of GARV-positive children whose diarrhoea was not the result of rotavirus infection, and as a consequence make no adjustment to these incidence figures to account for potential false-positive results. Incidence estimates assume that the proportion GARV positive in cases tested applies to all diarrhoea admissions whether or not tested. For children under 5 y of age, the incidence (per 100,000 per annum) of GARV-positive diarrhoea admissions was estimated at 478. For comparison, during the same period the incidence rates for admissions of under-5-y-olds with severe or very severe pneumonia, bacteraemia, or a final diagnosis that included malaria were 2,125, 325, and 2,639, respectively. Variation between sublocations of the DSS in the incidence of GARV-positive diarrhoea for children under 5 y is shown in Figure 1. For residents living near KDH the annual incidence of GARV-positive diarrhoea admissions in children < 5 y was estimated at 839 (95% CI 779–901) as opposed to 354 (95% CI 332–377) for residents from further away.
Severity of Diarrhoea and Concurrent Illness by Rotavirus Status
The clinical and laboratory features of GARV-positive and GARV-negative cases are compared in Table 3. Relative to GARV-negative cases, GARV-positive children presented with acute nonbloody diarrhoea or vomiting more frequently, and had a higher prevalence of life-threatening complications at admission including severe dehydration (sunken eyes), deep breathing (a correlate of metabolic acidosis), and severely perturbed biochemical parameters (hypernatraemia, hypokalaemia, severe metabolic acidosis, or elevated creatinine, but not hyponatraemia), all of which require prompt intravenous correction. Compared to the GARV-negative cases, GARV-positive children had a lower prevalence of concomitant illnesses including clinical pneumonia, malnutrition, and laboratory-confirmed malaria or bacterial infection (Table 3). The median age of GARV-positive cases (10 mo, IQR 7–15 mo) was significantly lower than that of GARV-negative cases (14 mo, IQR 9–25 mo) (p < 0.001). ORs for each feature, adjusted for potential confounding by age, retain the pattern described above (Table 3). The effect on this analysis of adjusting for distance from KDH (near versus far) was negligible and is not included.
Clinical, Laboratory, and Outcome Characteristics, Stratified by GARV Status, in Paediatric Diarrhoea Admissions to Kilifi District Hospital, Kenya 2002 to 2004
Bacterial pathogens were isolated from the blood of 13/588 (2%) GARV-positive cases and 96/1451 (6.6%) GARV-negative cases (Table 3). Isolates from GARV-positive patients included group A β-haemolytic streptococci (2), Staphylococcus aureus (1), Acinetobacter sp. (5), Pseudomonas sp. (2), Klebsiella sp. (2), and Salmonella sp. (1). Those from GARV-negative cases included Streptococcus pneumoniae (22), Escherischia coli (21), and Salmonella sp. (21), the remainder comprising group A β-haemolytic streptococci (9), Haemophilus influenzae (7), Acinetobacter sp. (6), S. aureus (5), Pseudomonas sp. (4), Campylobacter sp. (2), Klebsiella sp. (1), Shigella sp. (1) and a gram-negative coccus (1). In four GARV-negative cases two species were coinfecting.
Mortality and Duration of Hospital Inpatient Stay by GARV Status
The proportion of GARV-positive cases remaining in hospital for more than 12 d (3%) was significantly lower than that in GARV-negatives (16%) (Table 3). Mean durations of hospital stay were 5.2 d and 7.5 d, respectively. In-hospital mortality in GARV-positive cases was 2%, significantly lower than in GARV-negative cases (9%) (Table 3). Relative to GARV-negatives, the age-adjusted OR of death in GARV-positives was 0.21 (95% CI 0.11–0.41; p < 0.001). The differential in mortality is primarily attributable to the high prevalence of severe malnutrition amongst the GARV-negative group compared to GARV-positives (37% versus 14%, p < 0.001, Table 3), and concomitant higher case fatality in the GARV-negative, compared to GARV-positive, malnourished children (21% versus 6%, p = 0.001). Further analyses of factors associated with in-hospital mortality in diarrhoea cases are presented in Table S2 and Text S2.
Four of the GARV-positive children with diarrhoea who died had malnutrition and one had a lower respiratory tract infection. The mean annual number of in-hospital deaths among resident diarrhoea cases under 5 y old was 48, of which 3.6% were GARV positive. Similarly, the annual number of deaths in resident infant diarrhoea cases was 18, of which 4.9% were GARV positive. These data yield estimated rates (per 100,000 per year) of hospital deaths attributable to diarrhoea of 120 (95% CI 100–143) in children under 5 y, and 228 (168–301) in infants, and corresponding estimates of hospital deaths attributable to GARV-positive diarrhoea of 5 (2–11) and 9 (1–34), respectively (note that these are based on small numbers of deaths).
In our study, conducted in a rural district hospital in Kenya over a 3-y period, GARV was identified in 29% of children admitted with diarrhoea. The prevalence was highest in the youngest children: 38% in those < 1 y of age and 30% in under-5-y-olds. We estimated the annual incidence (per 100,000 population) of GARV-associated hospitalisations with acute severe diarrhoea at 1,275–1,600 in children under 1 y of age, 437–521 in children under 5 y, and 187–223 in those under 13 y, similar figures to those reported in industrialised nations with greater access to health care and diagnostic facilities . Our data suggest that in the area served by our hospital, over 1% of infants are hospitalised with severe GARV-associated diarrhoea each year. By 5 y of age, over 2% of children will have been hospitalised with GARV diarrhoea (Table 1); by extrapolation, therefore, given the under-5-y population of Kenya (5.98 million in 2005 ), in the nation as a whole an effective rotavirus vaccine could prevent in excess of 28,000 hospital admissions in this age group every year. Our incidence estimates include only the children who present to hospital with diarrhoea; the under-ascertainment implicit in this method is reflected by the fact that the estimated incidence was over 70% higher for the population immediately served by KDH than for the DSS as a whole. It is likely that our current study represents a conservative estimate of the true burden of rotavirus disease.
External validity of these data is an important consideration in making extrapolations. KDH paediatric care is unusually well resourced for a Kenyan district hospital. However, apart from mortality and in-patient stay, the characteristics of the study participants (detailed in Table 3) are determined at admission, and uninfluenced by in-patient management. Furthermore, there is no evidence that local knowledge of the high quality care at KDH influences admission rates. At the time of this study demographic and health indicators for Kilifi District were not dissimilar to much of Kenya .
Only a small proportion (3%) of children without diarrhoea (controls) were found to be GARV positive. This provides assurance that the vast majority of the observed GARV-associated severe diarrhoea is potentially GARV-vaccine preventable. Few studies have investigated the prevalence of rotavirus shedding in the absence of disease , and yet asymptomatic rotavirus infection [27–29] and prolonged excretion have both been reported in children [27,30,31], in particular in neonates. It is of interest that five of 19 positive controls in this study were less than 2 wk old, because subclinical infection and associated prolonged virus shedding, particularly within young infants, may play an important role in the spread of GARV infection. Consistent with previous studies we found that the major burden (85%) of GARV diarrhoea fell on children under 18 mo of age, and over 60% of cases were in infants. Of importance to the delivery of a vaccine within the current immunization schedule, the proportion of cases in children under 3 mo old was only 3% and in those under 6 mo was 18%.
From the clinical perspective, we found that relative to GARV-negative cases, the GARV-positive children with diarrhoea were more ill on admission, but their clinical signs and symptoms were mainly reflections of fluid loss and electrolyte imbalance and, therefore, readily corrected with the good supportive care available at this hospital. The GARV-negative children admitted with diarrhoea were less acutely unwell at admission but had a higher incidence of coexisting illnesses, such as malnutrition, that were less readily treated and consequently had worse outcomes. Compared with early work in the US we identify a similar clinical picture of higher prevalence of dehydration and vomiting, and short in-hospital stay, in rotavirus-infected relative to uninfected children, with similar age distribution of children with GARV infection but of lower prevalence. However, our findings of a marked differential in the degree of acidosis and electrolyte imbalance between the two groups were not previously identified. While we consider it unlikely that there was a substantial systematic bias in the distribution of severity characteristics (Table 3) attributable to the group of diarrhoea patients admitted who were not tested for GARV, or to patterns of admission related to distance, these are uncertainties that urge caution in the interpretation of the data.
A limitation with the present study is the bias inevitable with hospital-based surveillance in estimating community incidence of GARV severe diarrhoea and associated mortality. Such estimates are rooted in parental interpretation of what constitutes disease severe enough to warrant hospital attendance. Clearly, this will be linked to factors related to health care utilisation such as ease of access. Possible distortion of the distribution of severity in relation to distance, for example, resulting from children arriving from greater distances representing the more severe cases within their home areas, could lead to overestimation of GARV-positive diarrhoea severity relative to GARV-negative diarrhoea. A further limitation results from the failure to test around one-third of eligible children, and although its effect on the profile of GARV severe disease presented must be considered uncertain, we present some evidence that suggests it is not substantial.
Despite its importance in defining the need for rotavirus vaccines, data on GARV-associated mortality from developing countries are limited . The low mortality reported for cases in the current study may well reflect the fact that these children were ostensibly healthy individuals, and the acute life-threatening metabolic derangements we commonly recorded were readily reversed in the well-functioning setting of KDH. In the majority of African hospitals, which do not provide immediate fluid and electrolyte resuscitation, it seems likely that mortality from GARV would be very much higher.
Figure S1. GARV-Positive Diarrhoea Admissions to Kilifi District Hospital, Kenya, 2002–2004
Shown are monthly cases of diarrhoea (solid line), tests for GARV (dashed line), and GARV-positives (filled area), with corresponding mean daily rainfall (bars), maximum temperature (°C) (open diamonds), and relative humidity (closed triangles). Climate data was obtained from the national meteorological station Kilifi Institute of Agriculture, Kilifi, Kenya.
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Table S1. Characteristics of Patients with Diarrhoea Who Were Tested or Not Tested (NT) for GARV, for Children with a Final Diagnosis That Includes Gastroenteritis (GE) at Kilifi District Hospital, Kenya, 2002–2004
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Table S2. Fatality Proportions in Paediatric Diarrhoea Admissions to Kilifi District Hospital, Kenya, with or without a Range of Clinical and Biochemical Features
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Text S1. Implications of the Failure to Collect and Test a Proportion of Diarrhoea Cases
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Text S2. Indicators of High Risk of In-Hospital Mortality in Diarrhoea Cases
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We are indebted to the enrolled children and their caregivers, all staff of the paediatrics wards, in particular field workers who collected the samples, senior hospital personnel, and the DSS team. The Kilifi Household and Demographic Surveillance System (HDSS) is affiliated to the INDEPTH Network of Global HDSS sites. The study is published with permission of the Director of KEMRI.
DJN, AP, and TNW designed the study. JA and JKM undertook laboratory analysis, with training and guidance by IP and JD. Implementation, ward supervision and clinical data interpretation were undertaken by AP and KM. JAGS and TNW established the epidemiological DSS, which is coordinated by EB, and DSS data management is undertaken by HG. DJN led the statistical analysis with support from HG, JAGS, and TNW. DJN wrote the paper with critical revisions by JAGS, KM, and TNW. All authors made critical comments on the manuscript content, and all have approved the final submitted version.
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<urn:uuid:8e878993-fe9f-46b5-b54f-93581b26220d> | seed | Jan 5, 2005 (CIDRAP News) – A new study of human cases of H5N1 avian influenza in Thailand suggests that a number of cases might have gone undetected and that the disease may prey on children disproportionately.
Thai investigators reviewed 610 illness cases that occurred from January through March of 2004 and had features suggesting possible H5N1 infection. Twelve of those were confirmed as H5N1, and 7 of the 12 patients were children younger than 14 years, according to the report, published online by Emerging Infectious Diseases.
Because up to 61% of rural residents in Thailand have regular contact with backyard poultry flocks, "The 12 cases we report likely represent the end result of hundreds of thousands of potential exposures and an unknown number of human cases," the report states. It was written by Tawee Chotpitayasunondh, a pediatric infectious disease specialist at Queen Sirikit National Institute of Child Health in Bangkok, and colleagues.
They suggest that H5N1 cases are not easily detected because the disease has few distinctive clinical features and specific diagnostic tests are not widely available. The illness typically involves pneumonia, but pneumonia due to other causes is fairly common in rural Asia.
"Human infections with highly pathogenic avian influenza may be easy to miss in the context of the regular incidence of pneumonia in much of rural Asia, where the capacity to make specific etiologic diagnoses remains limited," the report says. The authors suggest that these circumstances may explain why "human cases have been few and have been reported only from Vietnam and Thailand."
The World Health Organization (WHO) has recognized 44 human cases of H5N1 avian flu in the past year, including 27 in Vietnam and 17 in Thailand. Twenty cases in Vietnam and 12 in Thailand have been fatal. The official WHO count does not include two cases reported in Vietnam in the past week. A case in a 16-year-old girl was reported last week, and news services today reported a fatal case in a 9-year-old boy.
Disease experts fear that the H5N1 virus may spark a human flu pandemic if it finds a way to spread easily from person to person. Only one possible case of person-to-person transmission has been recorded so far.
The Thai investigators examined all cases in the first 3 months of 2004 in which patients were hospitalized with pneumonia or influenza after exposure to sick poultry. They classified cases with laboratory evidence of H5N1 infection as confirmed. Cases in which patients had been exposed to sick poultry and had either severe pneumonia or laboratory evidence of influenza A, but without confirmation of H5N1, were defined as suspected.
The researchers found 12 confirmed and 21 suspected H5N1 cases among the 610 potential cases reported from 67 of Thailand's 76 provinces. Eight of the 12 confirmed case-patients died. The median age of the confirmed patients was 12 years (range, 2 to 58) and that of the suspected patients was 33 (range, 1-67).
All the confirmed patients came from villages where abnormal chicken deaths had occurred, and nine lived in houses where backyard chickens had died unexpectedly, the article says. Eight patients had had direct contact with dead chickens.
All the case-patients had fever, cough, and dyspnea when they were hospitalized, and 5 of the 12 had myalgia and diarrhea. Chest radiographs were abnormal in all the cases. In the late stages of the illness, nine patients suffered respiratory failure and five had cardiac failure. The patients who died had a significantly lower lymphocyte count at hospital admission than those who survived.
The 12 patients were all treated with broad-spectrum antimicrobials, and seven were also treated with the antiviral drug oseltamivir. Two of the patients who received oseltamivir survived the illness. The survivors started oseltamivir treatment a median of 4.5 days after the onset of symptoms, versus 9 days for those who died despite treatment with the drug.
"We advocate using this agent in the early treatment of case-patients with suspected H5N1 influenza, in agreement with the recommendations of WHO," the authors say.
The investigators advocate specific testing for H5 influenza when a patient has a history of contact with sick poultry, young age, pneumonia and lymphopenia, and progression to acute respiratory distress syndrome.
The researchers suggest that recent H5N1 cases have been more severe than the 18 H5N1 cases that occurred in Hong Kong in 1997. Six, or 33%, of the Hong Kong patients died, as compared with 68% of patients reported in 2004 at the time the report was written. "Several lines of evidence indicate that the H5N1 viruses have evolved to more virulent forms since 1997, with different antigenic structure, internal gene constellations, and an expanded host range," the report states. "This virologic evolution may be a factor in the persistence of H5N1 viruses in the avian populations."
Chotpitayasunondh T, Ungchusak K, Hanshaoworakul W, et al. Human disease from influenza (H5N1), Thailand, 2004. Emerg Infect Dis 2005 Feb;11(2) [Full text] |
<urn:uuid:c43c4030-6a2f-48b5-8b50-963866e7c81c> | seed | PAGE 2 OF 4
Richard Lifton helped make exome sequencing viable and has used it to make discoveries in blood pressure control and cancer.
Scientists had no way to quickly sequence many genes at once. They could painstakingly sequence the genes one by one, or they could sequence an entire human genome—far more expensive and just as time-consuming.
Finally, in 2009, a new automated method opened the floodgates. Called exome sequencing, it allows researchers to quickly piece together the sequence of the exome, the 1 percent of the genome that encodes proteins. Focusing on this small portion, where many disease-related genes had already been found, made sense.
“The goal of my lab used to be to identify one disease gene per year; now, we’re identifying one or two per week. It’s like a dam opening up.”
Joseph G. Gleeson
Researchers admit, however, that exome sequencing ignores mutations in the other 99 percent of the genome—the regulatory sequences that influence whether a protein is made or how much is produced plus the stretches of nucleotides with unknown functions. And there’s no shortcut for interpreting the data that come from exome sequencing. So, when the cost of whole genome sequencing drops, exome sequencing will likely become obsolete. But, for now, it’s giving scientists a head start on studying the human genome.
In October 2010, barely a year after the first reports of exome sequencing being used to locate disease genes, Walsh published the gene mutations responsible for one form of microcephaly. He used exome sequencing to burrow into the 148 genes on chromosome 19 and found that mutations in WDR62, a gene expressed in developing neurons, are involved. Within months, before and after Walsh’s discovery, two other labs used exome sequencing to do the same thing—and replicated Walsh’s results.
“It was a mountain that no one could climb and then as soon as the tools were developed to make it easier, everybody could do it,” says Walsh. Today, for many labs, exome sequencing is the go-to method to pin down genetic mutations responsible for rare diseases. And researchers who study more common afflictions—like heart disease and autism—are using it to make inroads as well.
For some researchers, exome sequencing is allowing findings that never would have been possible without the method. For others, it’s speeding the pace of discovery.
“The goal of my lab used to be to identify one disease gene per year,” says HHMI investigator Joseph G. Gleeson, who studies the genetics of pediatric brain disorders at the University of California, San Diego. “Now, we’re identifying one or two per week. It’s like a dam opening up.”
Before 2009, Gleeson, Walsh, and others who wanted to find the gene mutations responsible for an inherited disorder had to build extensive pedigrees of families with the disease. The more family members they could find, the better the odds of uncovering the relevant mutations. Then, they used genetic linkage studies—a classic technique based on observations made in the late 1800s—to narrow down the location of the mutation.
When egg and sperm cells form, genetic material is shuffled between matching chromosomes to form unique combinations. The idea behind genetic linkage is that genes closest to each other are likely to stick together and be inherited as a bundle after this shuffle. So by finding known genes shared by family members with a disorder—and lacking in those without the disorder—scientists can deduce that the disease-causing mutation is nearby. But linkage studies are tedious—researchers must test dozens of family members for genetic markers. Even once they crunch the numbers, they are often left with a large swath of chromosome that may or may not contain the mutation they’re looking for.
Each exome segment within this area must then be individually isolated and sequenced using a series of reactions. “In a typical project, there might be 200 genes in your candidate sequence and you were faced with running thousands of reactions to test for potential mutations,” Gleeson recalls.
Photo: Brian Park |
<urn:uuid:c18be101-6dbc-41ae-9495-a6aef87e7088> | seed | De Nove Genome Sequence Assembly
An organism's genome consists of base pairs (bp) from two strands of complementary bases. Reading a sequence of these bases or base pairs is termed as genome sequencing. This process is central to the study of genomes for bioinformaticians. No current sequencing technology is capable of reading the code of life in its entirety in one go. Instead, these machines output a large number of genome fragments called reads. Typically, the number of reads is in the millions or even billions. Sequence assembly refers to arranging and merging the reads into longer contiguous subsequences (contigs) with the goal of reconstructing the original sequence. In de novo sequence assembly, no reference sequence is used to aid the reconstruction process.
Recent Next Generation Sequencing (NGS) technologies produce a very large number of reads in a short amount of time. They have reduced the experimental cost per base significantly with their high throughput. This way they have opened up opportunities to study organisms at the genome level, promising a deeper understanding of genome regulation and biological mechanisms. A thorough study can assist in designing more effective drugs to cure diseases. Moreover, with NGS technologies researchers can study the evolution of viruses and bacteria at an unprecedented pace, for example during a recent E. coli outbreak in Europe. Such studies can for example help to accelerate vaccine development.
The large data produced by sequencing machines requires an efficient assembly process in terms of running time and memory consumption. Our assembler PASQUAL, short for PArallel SeQUence AssembLer, is designed for shared memory parallelism, using OpenMP due to its good tradeoff between performance and programmer productivity. Shared memory parallelism has become mainstream with the widespread production of multicore commodity processors. For PASQUAL we follow the OLC approach and use a careful combination of tailored algorithms and data structures to obtain high-quality solutions.
Our experimental results show that, given enough CPU cores, our multi-threaded PASQUAL implementation is faster than any other tool we could run on our test platforms. PASQUAL is capable of handling data with billions of bases, thus enabling biologists to assemble larger data sets in less time. Unlike SOAPdenovo, which is the only tool with comparable (or in several experiments with smaller CPU core numbers even better) speed, PASQUAL is not restricted to k-mer (or overlap) lengths smaller than 128—and PASQUAL produces significantly fewer assembly errors. |
<urn:uuid:09f8339e-d20a-434b-8233-e048d7406db7> | seed | Dysentery affects the large intestine and it is characterized by inflammation and ulceration of the bowel.
Dysentery is a serious condition affecting the large intestine caused by two organisms, protozoa and bacilli. The former is generally known as amoebic dysentery and the latter as bacillary dysentery. An attack of amoebic dysentery is milder in comparison with bacillary dysentery. But while bacillary dysentery can respond quickly to treatment, amoebic dysentery is very difficult for the patient to get rid of this dysentery.
Dysentery is characterized by inflammation and ulceration of the bowel, which is a colic pain in the region of the abdomen and passing of liquid or semi-formed stools with mucus and blood.
Symptoms of Dysentery:
Dysentery may be acute and chronic. The symptoms of each of them are as follows:
This is characterized by pain in the abdomen, diarrhoea and dysenteric motions, where yellowish white mucus and sometimes only blood from the intestinal ulcers passes with stools.
Pain and tenesmus precede the evacuations.
The patient feels a constant desire to evacuate, although there may be nothing to throw off except a little mucus and blood.
There is a feeling of pain in the rectum and along the large intestine.
With the advance of the disease the quantity of mucus and blood increases. Occasionally icasts or shreds of skin like mucous membrane, from small fragments to about 12 inches in length and an inch wide, are seen to pass out with motions. Sometimes pus is also thrown out with motions and often the smell of the stools becomes very unbearable.
All the digestive processes are upset and secretions are changed or stopped.
The saliva becomes acidic instead of being alkaline and the gastric juice itself may become alkaline.
The stomach loses power to digest and absorb food. The bacilli create toxins and the faecal matters formed also increase the further manufacture of toxins and their consequent absorption in blood.
Chronic cases are after-effects of acute attacks, where the patient does not recover completely.
The stools remains putrid and may contain blood, while diarrhoea and constipation may alternate, and general health is disturbed.
In severe cases, the temperature may also rise. It may occasionally become subnormal also.
Causes of Dysentery:
The cause of dysentery, according to modem medical system, is germ infection, since the latter develop in the colon as a result of putrefaction of excessive quantities of animal protein food, fried substances, over-spiced foods and hard to digest fatty substances. However, the real cause of dysentery is the dietary indiscretion and eating of excessive amounts of flesh food in hot weather or tropical climate unsuited to the digestion of such foods. Other causes also include debility, fatigue, chill, lowered vitality, intestinal disorders and overcrowding under unsanitary conditions.
Treatment of Dysentery by Nature Cure:
The treatment of dysentery aims at:
Removing the faecal and toxic matter from the intestines
Alleviating the painful symptoms
Stopping the virulence of the bacteria
Promoting the healing of the ulcer.
Here are a few treatments to go ahead with treating this disease in its acute form.
The patient should fast as long as acute symptoms are present, where he should intake only orange juice and water. Alternatively, the patient should also subsist on buttermilk till the acute symptoms are over, since buttermilk combats offending bacteria and helps establishment of helpful microorganisms in the intestines.
The patient may also be given small doses of castor oil, since this acts as a mild prerogative and facilitates quicker removal of offensive matter, minimizes the strain during motion and also acts as a lubricant to the ulcerated surfaces.
The removal of accumulated poisonous matter should be attempted by giving very low-pressure enema, twice or thrice daily.
The patient should also take complete bed rest as movement induces pain and aggravates distressing symptoms.
A hot water bag may also be applied over the abdomen.
Chronic Form of Dysentery:
After the acute symptoms are over, the patient may be allowed rice, curd, fresh ripe fruits, especially banana, pomegranate and skimmed milk.
Solid foods should be introduced very carefully and gradually according to the pace of recovery, however avoided flesh foods of all kinds as far as possible.
Other foods, which should be avoided are tea, coffee, white sugar and white flour and products made from them as well as alcohol in all forms.
The use of pomegranate rind is another effective remedy for dysentery. About 60 grams of the rind should be boiled in 250 grams of milk. It should be removed from the fire when one third of the milk has evaporated. It should be administered to the patient in three equal doses at suitable intervals.
Lemon juice is very effective in dealing with ordinary cases of dysentery. A few lemons, peeled and sliced, should be added to 250 ml. of water and boiled for a few minutes and this should be strained and taken thrice daily.
Other remedies considered useful in the treatment of dysentery are the use of small pieces of onions mixed with curd and equal parts of tender leaves of the peepal tree, coriander leaves and sugar chewed slowly.
(Last Updated on : 21/02/2014) |
<urn:uuid:9275b5c0-52bc-4948-8d61-fa3da5bfba97> | seed | Martyn D Kirk
This issue of Communicable Diseases Intelligence contains several reports highlighting the importance of enteric infections. Infections spread via the faecal-oral route result in significant social and economic costs, regardless of a country’s level of industrialisation.1 In Australia, the burden of disease transmitted by contaminated food was estimated to cost AUD$1.2 billion annually.2 Data from the OzFoodNet network (www.ozfoodnet.gov.au) was critical to estimating these costs, which are largely driven by lost productivity due to people taking time off work as a result of their own illness or to care for someone else who was ill. OzFoodNet is a national network of epidemiologists, which has dramatically improved public health action for enteric infections.3 A simple example of how OzFoodNet has improved the surveillance of enteric infections is shown in the number of outbreaks of gastroenteritis and foodborne disease reported over time. In 2002, OzFoodNet reported 513 foodborne and gastrointestinal outbreaks compared with 1,640 outbreaks in 2010, indicating a much-matured surveillance system.4,5
Rotavirus is a common cause of gastroenteritis and one of the most significant enteric pathogens globally due to the resulting high mortality in young children, particularly in low-income countries.6 Various studies have highlighted the impact that the introduction of rotavirus vaccines into the Australia immunisation schedule has had on public health, which is reinforced in the article by David and Kirk in this issue.7–9 Also in this issue is a report of molecular surveillance of rotavirus in Australia that shows a dynamic pattern of circulating wild-type strains, highlighting the importance of prospective surveillance to monitor the epidemiology of rotavirus in a post-vaccine era.10
Enteric infections often manifest as gastroenteritis consisting of vomiting and diarrhoea, but may also result in more serious outcomes, such as hepatitis, meningitis, or bacteraemia. Determining the mode of transmission of enteric agents is often challenging, as there are usually multiple means of transmitting illness.11 For example, norovirus is one of the most common causes of infectious gastroenteritis globally and is highly-infectious.12 The virus may be transmitted by contaminated food, water, or from contact with another infected person or contaminated fomites.13 The two reports of outbreaks of norovirus associated with oysters in northern New South Wales and Tasmania respectively, highlight the risks that occur when filter-feeding molluscs are grown in water contaminated by human sewage.14,15 In Australia, oyster related outbreaks are rare due to the safeguards instituted by industry and government, although they can still occur where there are breakdowns in sanitation, which occurred in these two outbreaks. Data from the OzFoodNet network illustrate that most outbreaks of norovirus are spread from one infected person to another, particularly in institutionalised settings.5,16 It is likely that vaccines against noroviruses will be produced in the future due to the potential economic and public health benefits.17
The investigation of hepatitis A infections transmitted by sharing Kava on page E26 demonstrates the highly infectious nature of the virus.18 In recent years, the incidence of hepatitis A infections in Australia has declined significantly.19 Many cases of hepatitis A reported to health departments in Australia are in travellers returning from overseas, including Pacific Island countries and territories (http://www.health.nsw.gov.au/Infectious/alerts/Documents/Hepatitis_A_Alert_8March2013.pdf).20,21 The three additional cases (along with an additional tertiary case) of hepatitis A that occurred in this cluster after sharing kava with the primary case while they were infectious provides some clues as to how people acquire infection when travelling to Pacific Island countries and territories and illustrates the need for vaccination for travellers to the region.22 While the incidence of locally-acquired cases in Australia is low, the outbreak due to imported semi-dried tomatoes in 2008–09 highlights that Australia is vulnerable to large and serious foodborne outbreaks of hepatitis A.23
Finally, this issue also includes two articles highlighting the public health response to clusters of two important bacterial infections due to Salmonella Typhi in a family and Campylobacter associated with duck livers.24,25 In particular, the outbreak of campylobacteriosis is very similar to other previously reported outbreaks where food premises have served undercooked poultry livers in Australia and overseas.26–28 The short incubation period demonstrates that the cooking process was inadequate and that affected persons were likely to have received large doses of Campylobacter from the contaminated dish.
Associate Professor Martyn D Kirk, Head, MAE Program, National Centre for Epidemiology and Population Health, Australian National University, CANBERRA ACT 0200. Telephone +61 2 6125 5609. Fax +61 2 6125 0740. Email: martyn.kirk AT anu.edu.au
- Rocourt J, Moy J, Vierk K, Schlundt J. The present state of foodborne disease in OECD countries. Geneva: The World Health Organization; 2003.
- Abelson P, Potter-Forbes M, Hall G. The Annual Cost of Foodborne Illness in Australia. Canberra: Commonwealth of Australia; 2006.
- Kirk MD, McKay I, Hall GV, Dalton CB, Stafford R, Unicomb L, et al. Food safety: foodborne disease in Australia: the OzFoodNet experience. Clin Infect Dis 2008;47(3):392–400.
- OzFoodNet Working Group. Foodborne disease in Australia: incidence, notifications and outbreaks. Annual report of the OzFoodNet network, 2002. Commun Dis Intell 2003;27(2):209–243.
- OzFoodNet Working Group. Monitoring the incidence and causes of diseases potentially transmitted by food in Australia: annual report of the OzFoodNet network, 2010. Commun Dis Intell 2012;36(3):E213–E241.
- Walker CL, Rudan I, Liu L, Nair H, Theodoratou E, Bhutta ZA, et al. Global burden of childhood pneumonia and diarrhoea. Lancet 2013;381(9875):1405–1416.
- Buttery JP, Lambert SB, Grimwood K, Nissen MD, Field EJ, Macartney KK, et al. Reduction in rotavirus-associated acute gastroenteritis following introduction of rotavirus vaccine into Australia’s National Childhood vaccine schedule. Pediatr Infect Dis J 2011;30(1 Suppl):S25–S29.
- Dey A, Wang H, Menzies R, Macartney K. Changes in hospitalisations for acute gastroenteritis in Australia after the national rotavirus vaccination program. Med J Aust 2012;197(8):453–457.
- David RL, Kirk MD. Rotavirus gastroenteritis hospitalisations following introduction of vaccination, Canberra. Commun Dis Intell 2014;38(1):E3–E8.
- Kirkwood CD, Roczo-Farkas S, Bishop RF, Barnes GL, and the Australian Rotavirus Surveillance Group. Australian Rotavirus Surveillance Program annual report, 2012. Commun Dis Intell 2014;38(1):E29–E35.
- Pires SM, Evers EG, van Pelt W, Ayers T, Scallan E, Angulo FJ, et al. Attributing the human disease burden of foodborne infections to specific sources. Foodborne Pathog Dis 2009;6(4):417–424.
- Siebenga JJ, Vennema H, Zheng DP, Vinjé J, Lee BE, Pang XL, et al. Norovirus illness is a global problem: emergence and spread of norovirus GII.4 variants, 2001–2007. J Infect Dis 2009;200(5):802–812.
- Bitler EJ, Matthews JE, Dickey BW, Eisenberg JN, Leon JS. Norovirus outbreaks: a systematic review of commonly implicated transmission routes and vehicles. Epidemiol Infect 2013;141(8):1563–1571.
- FitzgeraldT-LL, Zammit A, Merritt TD, McLeod C, Landinez LM, Whote PA, et al. An outbreak of norovirus genogroup II associated with New South Wales oysters. Commun Dis Intell 2014;38(1):E9–E15.
- Lodo KL, Veitch MGK, Green ML. An outbreak of norovirus linked to oysters in Tasmania. Commun Dis Intell 2014;38(1):E16–E19.
- Kirk MD, Fullerton K, Hall GV, et al. Surveillance for outbreaks of gastroenteritis in long-term care facilities, Australia, 2002–2008. Clin Infect Dis 2010;51(8):907–914.
- Bartsch SM, Lopman BA, Hall AJ, Parashar UD, Lee BY. The potential economic value of a human norovirus vaccine for the United States. Vaccine 2012;30(49):7097–7104.
- Parker J-AM, Kurien TT, Huppatz C. Hepatitis A outbreak associated with kava drinking. Commun Dis Intell 2014;38(1):E26–E28.
- NNDSS Annual Report Writing Group. Australia’s notifiable disease status, 2011: Annual report of the National Notifiable Diseases Surveillance System. Commun Dis Intell 2013;37(4):E313–E393.
- Zwar N, Streeton CL, Travel Health Advisory G. Pretravel advice and hepatitis A immunization among Australian travelers. J Travel Med 2007;14(1):31–36.
- Leder K, Torresi J, Libman MD, Cramer JP, Castelli F, Schlagenhauf P, et al. GeoSentinel surveillance of illness in returned travelers, 2007–2011. Ann Intern Med 2013;158(6):456–468.
- Wilder-Smith A, Khairullah NS, Song JH, Chen CY, Torresi J. Travel health knowledge, attitudes and practices among Australasian travelers. J Travel Med 2004;11(1):9–15.
- Donnan EJ, Fielding JE, Gregory JE, Lalor K, Rowe S, Goldsmith P, et al. A multistate outbreak of hepatitis A associated with semidried tomatoes in Australia, 2009. Clin Infect Dis 2012;54(6):775–781.
- Hope KG, Merritt TD, Durrheim DN. Short incubation periods in Campylobacter outbreaks associated with poultry liver dishes. Commun Dis Intell 2014;38(1):E20–E23.
- Scott NS, Paterson JM, Seale H, Truman G. Chronic carriage and familial transmission of typhoid in western Sydney. Commun Dis Intell 2014;38(1):E24–E25.
- Abid M, Wimalarathna H, Mills J, Saldana L, Pang W, Richardson JF, et al. Duck liver-associated outbreak of campylobacteriosis among humans, United Kingdom, 2011. Emerg Infect Dis 2013;19(8):1310–1313.
- Centers for Disease Control and Prevention. Multistate outbreak of Campylobacter jejuni infections associated with undercooked chicken livers—northeastern United States, 2012. MMWR Morb Mortal Wkly Rep 2013;62(44):874–876.
- Parry A, Fearnley E, Denehy E. ‘Surprise’: Outbreak of Campylobacter infection associated with chicken liver pate at a surprise birthday party, Adelaide, Australia, 2012. Western Pac Surveill Response J 2012;3(4):16–19. |
<urn:uuid:d522dca6-7069-4ca6-b016-05fb161da6e6> | seed | It’s long been known that black Americans are four to five times as likely as white Americans to suffer from kidney disease that is severe enough to require dialysis or transplantation. Now a new study conducted by researchers at the University of California, San Francisco (UCSF) and San Francisco VA Medical Center (SFVAMC) shows that rates of early kidney disease do not differ between the two groups, but that blacks with early disease are five times as likely as whites to progress to the severe stage that requires dialysis or transplantation. The findings suggest that black Americans with early kidney disease require much more aggressive treatment than has been commonly practiced.
“Black Americans make up a third of the dialysis population, but only about a tenth of the overall population. But nobody has ever looked at whether blacks have more early kidney disease than whites,” says Chi-yuan Hsu, MD, lead author of the study and an assistant professor of medicine at UCSF. “What we found is that the two groups have the same amount of kidney disease, but if someone has early disease and they are white, their chances of going to dialysis are one in 100 per year. But if they are black, their chance is five times higher.”
The study appears in November’s Journal of the American Society of Nephrology. Senior investigator in the study is Michael Shlipak, MD, MPH, assistant professor of medicine, epidemiology and biostatistics at SFVAMC and UCSF.
In the United States, the two major risk factors for kidney disease are uncontrolled diabetes and hypertension (high blood pressure). Early kidney disease, also called chronic renal insufficiency, is a gradually progressing disease that if left untreated can result in end-stage renal disease, the point at which kidneys fail. Without a kidney transplant or dialysis—a blood-filtering process that must be performed several times a week—a person suffering from end-stage kidney disease will die. Although statistics for end-stage kidney disease and its treatments are tracked through a comprehensive national registry (the U.S. Renal Data System), early-stage kidney disease can go undetected for years, making its onset and progression difficult to detect.
In order to determine the prevalence of the earlier stages of disease, Hsu and his team turned to a national health survey conducted periodically by the Centers for Disease Control called NHANES, or the National Health and Nutrition Examination Survey. The survey uses interviews and a battery of tests to assess the health of a representative sample of people across the country. Survey results are then extrapolated to the U.S. population as a whole.
Using records from blood tests drawn during the 1988-1994 survey, Hsu and his team used a formula to estimate the glomerular infiltration rate—a measure of kidney function—of each of the survey’s black and white participants aged 20 to 74, a total of 13,351 people. They found that about 2 percent of blacks and 2.5 percent of whites had early kidney disease, a difference that was not statistically significant. To estimate how many people progressed to end-stage kidney disease five years later, they examined U.S. Renal Data System records for the number of new cases of end-stage kidney disease that arose in 1996 among black and white adults 25 to 79 years old. They found that for each 100 white people identified as having early kidney disease in 1991 (the mid-point of the NHANES survey), one went on to develop end-stage disease in 1996. But for each 100 black people with early kidney disease in 1991, five developed end-stage disease in 1996.
“We were very surprised to find that blacks didn’t have more early kidney disease than whites,” Hsu says. “We thought we would find that they had more kidney disease at all the stages.”
Black Americans are more than twice as likely as white Americans to have hypertension, and one-and-a-half to two times as likely to have diabetes. Hsu found that black participants with early kidney disease in the NHANES survey had higher blood pressure than whites, with average systolic and diastolic pressures of 147 and 82, versus 136 and 77. Yet he also found that diabetic blacks and white survey participants with early kidney disease had similar blood sugar levels (an indication of how well diabetes is being controlled). Differences in blood pressure are unlikely to completely explain the five times higher rate of progression to end-stage disease, Hsu says. “We don’t know the causes for this disparity,” he says. “It could be quality of care and access to health care.” A genetic component can’t be ruled out, either, he says.
Based on this study’s findings, Hsu and colleagues suggest that the National Kidney Foundation modify its Chronic Kidney Disease classification system to take into account the risk of progression of the disease. Right now a black person and a white person with chronic renal insufficiency would both be classified as having stage 3 or 4 chronic kidney disease. “But the implications of suffering stage 3 or 4 disease are very different for blacks and whites,” Hsu says. “Our study suggests that a black person even with mild kidney disease should be treated much more aggressively. They should certainly attain at least as good blood pressure control, and they may need much more close monitoring and follow-up. The disparities we found in blood pressure control and progression rate from early to end-stage kidney disease must be addressed.”
More than 400,000 Americans with end-stage renal disease are being treated by dialysis. With the country’s population growing older and rates of diabetes soaring in large part due to increasing incidence of obesity, this number has more than doubled in the past decade, and is projected to grow to 650,000 by 2010, costing the Medicare system alone $28 billion.
Other investigators in the study were Feng Lin, MS, and Eric Vittinghoff, PhD, both from the department of Epidemiology and Biostatistics at UCSF. The study was funded by the National Institutes of Health and the Department of Veterans Affairs. |
<urn:uuid:5a34ccca-b3f5-4827-a44f-f40524d2ae34> | seed | A recent paper describes how the mutation of a single gene is sufficient to turn a harmless bacterium found in our gut into an invasive pathogen. Taken alone, this isn’t terribly surprising; many genes regulate the expression of other genes and some (“master” genes) act as switches that control a whole host of other genes. The gene mutated in this study isn’t one of these “master” genes, though; it’s a structural gene and there’s a much more intriguing reason for its broad impact on the bacterium.
Escherichia coli is a rod-shaped bacterium often found in the intestines of warm-blooded animals, including humans. They are often harmless (or even useful — our gut bacteria are important!), but some types (“strains”) may cause illness or food-poisoning. For example, the strain E. coli O104:H4 was responsible for the food-poisonings (traced back to German sprouts) in May of last year.
E. coli K-12 is a strain isolated from the human gut in 1922. In the 1970s, it became the workhorse for molecular biology because of its noninvasive, extracellular, benign commensal nature — in other words, because it’s a harmless bug that lives in our gut but doesn’t get into our cells. We know that under a wide range of conditions and in various animals, K-12 doesn’t invade its host’s cells or behave as a pathogen; in fact, the lab strain has even lost the ability to thrive in the human gut. These characteristics are the reason that the pioneers of the genetic age selected K-12 for their work. It became widely used throughout molecular genetics research and is still used in many labs today (along with derivative strains). In 1997, it was one of the first organisms to have its genome sequenced. As a result of being at the center of molecular biology for nearly 40 years, it may well be the best characterized life form on the planet. Although K-12 isn’t normally virulent, there are virulence genes in its genome, a fact which has puzzled scientists. We generally expect unused genes to disappear or acquire many mutations over time, but neither of those seems to be the case here.
In a study published this September in mBio, Koli and her colleagues found that the mutation of a single gene was enough to reactivate these virulence genes, transforming K-12 into a very different kind of bacterium. Not only did it gain the ability to invade cells, but a whole suite of genes was simultaneously activated. Some of the genes are clearly virulence-related, enabling it to replicate inside host cells and decreasing the production of a protein that would prematurely kill host cells; others have more general functions, leading to a change in the bacteria’s shape (from rod-like to spherical) and its metabolism, as well as giving it a wider temperature tolerance. The fact that the mutation of a single gene can affect such a range of traits isn’t surprising. The gene could be for a “transcription factor”, which is a molecule that bind to DNA and activate other genes; it’s not inconceivable that a mutant form of a transcription factor could activate a whole slew virulence genes in K-12. That’s not what’s happening, though, which is what makes this story so interesting. Instead, the mutation is in a gene encoding a structural protein that forms a kind of scaffolding for DNA.
A surprising fact about DNA is how very long the molecule actually is. Each of your cells contains about 1.8m (nearly 6 ft) of DNA coiled up inside it. At 1.5mm (a bit less than 1/16 of an inch) long, the DNA inside an E. coli is much shorter, but it’s still much larger than the E. coli cell, which is only about 0.002mm long. DNA has to be intricately packaged in order to fit inside a cell. In our cells (and the cells of other animals, plants and fungi), this is accomplished by winding the DNA around proteins called “histones”; a good analogy is the way a string (DNA) is wound around a spool (the histone). There are actually several different histones which interact to form units called nucleosomes, which then also form a helix, packing the DNA even more tightly; I managed to find a pretty good graphical representation for those who are more visually inclined. Bacteria don’t have histones, but they have “histone-like” proteins which perform similar roles; in E. coli, the histone-like proteins are HUa and HUb. The mutation that transformed the harmless E. coli K-12 line into an invasive form was in the gene encoding its HUa protein.
In addition to being wrapped around histones (or histone-like proteins), DNA is further compacted by something called “supercoiling”. Supercoiling is basically a description of the shape a DNA molecule takes when it is wound more tightly or more loosely. In a relaxed DNA molecule, there are a certain number of base pairs for every turn around the helix; changes in this number result in a physical strain on the molecule, which then changes its shape accordingly. A good analogy is the way a wire (like a headphone cable) or a rubber band twirls itself into complicated shapes if you twist it; a really good example is the way the handset wires on old telephones would twist around themselves. Depending on whether the DNA molecule is over- or under-wound, the supercoil spiral (“superhelix”) will twist one way or another; overwound DNA is positively supercoiled while underwound DNA is negatively supercoiled. The mutant histone protein in the invasive strain of E. coli K-12 causes the DNA to be more tightly wound, changing the superhelix from negative to positive supercoiling. The researchers were able to show that it was this change which resulted in the altered gene expression in the novel strain, dramatically altering the aspect and life-history of K-12.
The mutation of a single structural protein in the normally harmless K-12 strain of E. coli results in a conformational change of its entire DNA, exposing many genes and allowing them to become active (while the activity of other genes is repressed). We know that histones play a role in regulating gene expression in general, but this is a particularly striking example because of the dramatic nature of the change — it’s not just that a few genes were up- or down-regulated, but key aspects of the bacterium’s interaction with other cells were changed, as well as the shape and metabolism of the bacterium itself. It’s pretty intriguing to imagine what kind of role this sort of regulation could play, both in the short-term (e.g., stress response) and over the course of evolution. The fact that the up- and down-regulated genes in this example seem to be functionally co-ordinated suggests that this could be a very useful mechanism for efficient co-regulation of suites of functionally related genes, which could be selected together for activation (or repression) in positively or negatively supercoiled DNA. It’s also a wonderful example of the importance of form at every level of biology and a reminder that physical and spatial factors can have important biological consequences. I think it’s a beautiful story which teaches us something new while showing of how much we still have to discover.
Ref: Koli P, Sudan S, Fitzgerald D, Adhya S & Kar S. (2011) Koli, P., Sudan, S., Fitzgerald, D., Adhya, S., & Kar, S. (2011). Conversion of Commensal Escherichia coli K-12 to an Invasive Form via Expression of a Mutant Histone-Like Protein mBio, 2 (5) DOI: 10.1128/mBio.00182-11
(The paper is open access, which means you can read it without a subscription.)
[I decided to write about this paper after hearing about it on episode 18 of the podcast This Week in Microbiology, which is an excellent weekly podcast about the world of the very small. If you're interested in that sort of thing, give TWiM a try!] |
<urn:uuid:ac005730-f711-4d1d-b815-618ee5be07e7> | seed | This type of angina may be a symptom of coronary microvascular disease (MVD). Coronary MVD is heart disease that affects the heart’s smallest coronary artery blood vessels.Causes of microvascular angina: Spasms within the walls of these very small arterial blood vessels causes reduced blood flow to the heart muscle leading to a type of chest pain referred to as microvascular angina.
Symptoms of microvascular angina: Angina that occurs in coronary MVD may differ from the typical angina that occurs in heart disease in that the chest pain usually lasts longer than 10 minutes, and it can last longer than 30 minutes. If you have been diagnosed with MVD, follow the directions from your healthcare provider regarding how to treat your symptoms and when to seek emergency assistance.
The pain or discomfort:
- May be more severe and last longer than other types of angina pain
- May occur with shortness of breath, sleep problems, fatigue, and lack of energy
- Often is first noticed during routine daily activities and times of mental stress |
<urn:uuid:91a6f519-a561-4e97-8d73-648c1486fca0> | seed | High blood pressure is a major risk factor for cardiovascular disease and stroke. Data indicate that the prevalence of high blood pressure in children and adolescents has been on the rise since 1988, with African-American and Hispanic youths at greater risk. This is especially concerning since children with elevated blood pressure are more likely to have hypertension as adults. Further, increased atherosclerosis at higher blood pressure levels has been observed in the young. The following studies investigate the development, evaluation, and treatment of elevated blood pressure in pediatric populations.
The Impact of Malaria in Pregnancy on Changes in Blood Pressure in Children During Their First Year of Life
Fetal and early postnatal growth have been associated with blood pressure in adolescents and adults. Malaria, which is hyperendemic in Nigeria, is associated with a reduction in birth weight and early growth. This study of infants in Nigeria found that exposure to malaria while in utero correlated with sex-dependent effects on blood pressure that were independent of infant growth, from birth to 1 year of age.
Carotid Artery Intima-Media Thickness and Distensibility in Children and Adolescents
Carotid artery intima-media thickness (cIMT) has been used extensively to assess early, subclinical cardiovascular disease in children and young adults with known risk factors. Here, the authors establish reference data for cIMT and carotid artery distensibility in an international, healthy cohort of children and adolescents aged 6 to 18 years, which revealed a high impact of age, body dimensions, and blood pressure.
Combined Effects of Child and Adult Elevated Blood Pressure on Subclinical Atherosclerosis: The International Childhood Cardiovascular Cohort Consortium
While elevated blood pressure levels in childhood have been linked with future target-organ damage, less is known about whether these effects are reversible if blood pressure levels normalize by adulthood. This study of four cohorts from the International Childhood Cardiovascular Cohort Consortium found that participants with elevated childhood blood pressure and normal blood pressure in adulthood did not have a significantly higher risk of increased cIMT compared with individuals with persistently normal blood pressure.
Altered Genes Profile of Renin–Angiotensin System, Immune System, and Adipokines Receptors in Leukocytes of Children With Primary Hypertension
It is known that the renin-angiotensin system (RAS) is integral to blood pressure regulation, and a growing body of data indicating roles for both the innate and adaptive immune systems. This study highlights changes in the expression of RAS genes and CD14 in the peripheral blood leukocytes of children with primary hypertension after six months of lifestyle interventions, which also lowered blood pressure and normalized metabolic abnormalities.
Physical Activity and Blood Pressure in Primary School Children: A Longitudinal Study
The ability of physical activity to directly reduce blood pressure in adults has been well recognized, but less is known about this relationship in children. This study analyzed data from the predominantly South Asian cohort in the Birmingham healthy Eating and Active lifestyle for CHildren Study and found increased physical activity levels were associated with lower blood pressure in children as young as 5, independent of weight status. |
<urn:uuid:bdcde8f3-03a6-40c8-bf10-d4e0a443f591> | seed | A knowledge of normal anatomy is helpful in understanding how to treat a disease when things have gone wrong.
The Swallowing Mechanism
When learning about the normal workings of the gullet, stomach and diaphragm, the first element to understand is the action of normal swallowing. The only part of normal swallowing of which we are conscious takes place at the back of the tongue and in the throat area. From then on, once the food or the liquid reaches the top of the oesophagus, the process is an active but unconscious one that takes place in the oesophagus. This process is completed when the food or drink enters the stomach.
It is easy to imagine that the oesophagus is simply an inactive tube through which the food that we have swallowed passes by gravity to the stomach. However, what really takes place in swallowing is very different. We transfer food towards the back of the throat (the pharynx) using the tongue. Once the food reaches the pharynx, swallowing becomes automatic. In other words we can feel the food in our throat but we are unable to prevent the action of swallowing. The movement is now under the control of the autonomic nervous system, which also controls the movements of food through the rest of the digestive system without us being aware of it.
We can divide the autonomic (or subconscious) phase of swallowing into two sub phases: what takes place in the pharynx and what happens in the oesophagus.
In the Pharynx
When food or drink hits the pharynx (back of the throat), it stimulates two muscle reflexes. The first one shuts off the passages back into the mouth, the back of the nose, and the lungs. The second one squeezes the food down into the top of the oesophagus. The aim of this is to ensure that we do not inhale and swallow at the same time. If food or drink enters the lungs, it is a disaster that can lead to very sudden death or aspiration pneumonia.
In the Oesophagus
The oesophagus is a very muscular tube. The action of the autonomic nervous system causes it to contract and relax in a very coordinated fashion, so that it actively pushes liquids and solids onwards down into the stomach. These rippling muscle contractions are known as peristalsis. They take place throughout the whole length of the gut from the oesophagus, through the small intestines to the large intestine and to the anus. They are the means by which food and then faeces are passed onwards. If this process fails then food just sticks. Any liquid may trickle downwards, but solids will remain in a lump, stretching the walls of the tube and causing considerable pain and discomfort.
There are three recognisable types of muscular contraction in the oesophagus.
- Once we start to swallow, primary peristaltic waves ripple down the oesophagus, pushing food in front of them at a speed of approximately 5 cm per second.
- If the primary peristaltic waves are unable to manage to empty the contents of the oesophagus down into the stomach, then a second peristalsis wave commences, about halfway down the oesophagus. This reinforces the primary wave, and sometimes it may be felt as an uncomfortable almost indescribable feeling deep within the central chest.
- Tertiary muscle contractions in the oesophagus have been identified by radiologists who have vast experience of watching barium swallow x-rays. These tertiary muscle contractions take place in one segment of the oesophagus at a time. They do not appear to be involved in swallowing and they do not propel food onwards. Their purpose is not known, but it is possible that they are simply a way of maintaining the muscular tone of the oesophagus between meals, whilst waiting for the next piece of food to come down.
Peristalsis, both primary and secondary, is vital for transferring solid and semisolid food from the back of the pharynx into the stomach. As long as we are upright when we drink, however, peristalsis is not absolutely essential for liquids. Once we have swallowed some liquid, provided there is no obstruction to its flow, it will reach the stomach by gravity alone. However, peristalsis is required to ensure that food does not return upwards to the throat. Without peristalsis, if you were to swallow whilst lying flat or standing on your head, the food or drink would simply flow back into your mouth.
At its lower end, the oesophagus passes through a hole – the hiatus – in the diaphragm, which is a sheet of muscle that separates the contents of the chest from those of the abdomen. Below the diaphragmatic hiatus, the oesophagus becomes the upper part of the stomach. How it does so, and how it relates to the diaphragm, are crucial in determining whether or not a patient has a hiatus hernia.
The Junction of the Oesophagus and Stomach.
It is important that food flows in a one-way direction within the oesophagus, and it is even more vital that, once the food has reached the stomach, it remains there, and can only travel forwards into the duodenum. The digestive juices within the stomach are extremely acidic and are designed to digest proteins. The stomach wall is extremely well protected against its own acidic juices with a thick layer of mucus, to protect it against the protein digestive enzymes, and bicarbonate, to protect against acid. However, the oesophagus is not protected at all in this way. Therefore stomach juices that reflux up into the oesophagus are a powerful irritant. The acidic gastric juices can cause ulcers, inflammation, friability, erosions and eventually scarring and constriction at the lower end of the oesophagus.
Therefore, several mutually cooperative mechanisms exist in order to ensure that once food has passed into the stomach, it is unable to flow backwards up into the oesophagus.
The lower 5 cm or so of the oesophagus lie under the diaphragm within the abdominal cavity. The oesophagus meets the stomach at its upper right-hand surface, not quite at the top. If the stomach were the face of a clock, and you were looking at it from in front, then the junction between the oesophagus and stomach would lie at approximately 11 o'clock.
This junction is known as the cardia. It meets the stomach at an angle so that food slides easily into the bottom 90% of the stomach. This process is not unlike tipping a glass when you pour a drink into it, in order to to avoid froth and turbulence. The angle should also ensure that, if there is any reverse movement of food upwards inside the stomach, it passes by the entry from the oesophagus and ends up in the top part of the stomach, an area known as the fundus.
The fundus, which is the uppermost part of the stomach, acts as a safety valve and collects any gas that has been swallowed or produced during the process of digestion. The fundus of the stomach sits neatly underneath the diaphragm.
The Lower Esophageal Sphincter
At the cardia, just where the esophagus becomes the stomach, lies a ring of muscle, within the stomach wall. Try to imagine it like an elastic band around the tube, gripping it slightly and narrowing it. This is known as the gastroesophageal sphincter or lower oesophageal sphincter. There are sphincters at several important sites within the gut: apart from the one between the oesophagus and stomach, they also occur at the outlet of the stomach into the duodenum, between the small intestines and a large intestines and finally there is one at the anus which is the anal sphincter. These sphincters control the passage of food and food residues from one section of the digestive tract to the next. These sphincters prevent backflow of food and food residues.
So not only is the angle at which the oesophagus meets the stomach important, so also is the efficiency of the gastroesophageal sphincter. When it opens the ring of muscle relaxes to allow food and drink to pass from the oesophagus to the stomach. When it closes and the ring of muscle contracts it prevents the digested food in the stomach from flowing back up into the oesophagus. It is in effect a one-way valve.
In addition to the lower oesophageal sphincter muscles, another system of muscles keeps this above structure intact. These are the oblique muscle fibres within the wall of the oesophagus and stomach around the sphincter which keep the oesophagus and stomach at the appropriate angle to each other, in a sling-like support. Without the oblique muscles, the angle between the oesophagus and stomach would flatten out, and the bottom end of the oesophagus would be more open the backflow pressures.
Such backflow pressures are normal when the stomach, full of food, starts its job of digestion. Like the oesophagus, the stomach wall is subject to peristalsis, and although the movement is usually from the above going down, there are also chaotic churning waves, designed to mix the stomach contents thoroughly with the digestive juices of the stomach. If the sphincter and the oblique muscle fibres are not working properly, then this motion may force the stomach contents into the lower end of the oesophagus, which then leads to irritation of the oesophagus and the symptom of heartburn.
The abdominal pressure is an essential force which prevents backflow. There is a large difference between the pressures inside the thoracic and abdominal cavities. The pressure inside the thoracic cavity is kept relatively low, if not the lungs would be unable to expand. The pressure inside the abdominal cavity is much higher, because there are external pressures on the bowel helping to push its contents through and eventually out. The diaphragm is the muscular structure that maintains this large difference in pressure between the chest and abdominal cavities.
The diaphragm is a strong sheet of muscle that is attached in an umbrella-shaped circle around the lower margin of the ribs. Above the diaphragm are the lungs and heart. Below the diaphragm are the kidneys, the liver (on the right), the spleen (on the left), and the entire bowel from the stomach, through the small intestine and colon to the rectum and anus. The high pressure within the abdominal cavity means that if the muscles of the diaphragm are not working properly, some part of the contents of the abdominal cavity can be pushed through into the thoracic cavity. This is what is meant by a hernia.
There are holes in the diaphragm through which the oesophagus and the main blood vessels from and to the heart (the aorta and inferior vena cava) must pass. The blood vessels are at the back of the abdomen, just in front of the spine, but the oesophagus enters closer to the front of the diaphragm, through an opening of its own – the hiatus.
To ensure that nothing can slip upwards from the abdomen into the thoracic cavity through the hiatus there are strong muscles within the rim of the hiatus that hold it close to the oesophagus. These muscles are the diaphragmatic crura (from the Latin word for cross). These muscles crisscross around the oesophagus keeping it tightly in position.
This is an excellent setup, not only for preventing a hernia, but also for ensuring that the external pressure around the lower few centimetres of the oesophagus remains high. Therefore, even if the cardia is a bit inefficient and there is a risk that it may allow stomach contents to reflux up into the oesophagus, this is prevented simply by the high external pressure. This external pressure keeps the oesophagus collapsed until it is opened by the pressure of food and peristalsis. This external pressure applied to the lower part of the oesophagus is probably the most important mechanism for preventing the reflux of stomach acid into the lower oesophagus. When the cardia is pushed up into the chest cavity – as happens with a hiatus hernia – where the pressure around the oesophagus is much lower, then acid reflux from the stomach into the oesophagus becomes the rule, rather than the exception.
to be completed soon |
<urn:uuid:62ac7009-c9fa-4239-8a8d-5c3048451aea> | seed | Stem cells may one day provide a cure for deafness, if scientists can build on recent experiments in which a British research team grew the very delicate hair cells of the inner ear from fetal stem cells. These inner ear cells are crucial for hearing but are also irreplaceable and extremely frail. The new study marks the first time they’ve been grown in a laboratory.
The use of stem cells is promising because they can become any kind of cell in the body, and could thus not only be used to replace the lost hair cells, but also any damaged nerve cells along which the signals generated by the hair cells are transmitted to the brain [BBC]. The researchers grew the hair cells from cochlear stem cells they’d isolated from fetuses, cells which are only produced from 9 to 11 weeks into a pregnancy. “That’s why deafness is permanent, because we don’t have the stem cells to replace damaged cells in the ear” [New Scientist], says Marcelo Rivolta, lead researcher of the study published in the journal Stem Cells. The stem cells were taken from aborted fetuses, with full consent of the women involved.
After exposing the cells to various recipes of nutrients and growth factors, the team found one cocktail that changed the stem cells into human auditory hair-like cells. When mature, these grow fine hairs that bend in response to sound energy, generating electrical signals. A second recipe turned the stem cells into auditory neurons, the cells which receive signals from the hair cells and transmit them to the brain, which translates the messages into recognisable sound [New Scientist].
The scientists hope they will eventually be able to use the cells to perform cell transplants in deaf patients to replace the hair cells and neurons that are damaged in a form of deafness known as sensorineural hearing loss [The Telegraph]. Patients who would benefit would most likely include people who have lost hair cells because of noise damage, and some who inherited hearing problems at birth.
80beats: Forget the Hearing Aid: Why Not Regrow Inner Ear Cells?
80beats: UK Aims to Create “Unlimited” Supply of Synthetic Blood from Stem Cells
80beats: One Step Closer to Embryo-Free (and Controversy-Free) Stem Cells
80beats: Revealed: The Genetic Root of Seeing Sounds and Tasting Colors
Image: Flickr / shareski |
<urn:uuid:d99f1c33-9bd6-4277-8c9c-4b3c3c3b83d2> | seed | 'Holy Grail' of Hearing: True Identity of Pivotal Hearing Structure Is Revealed
EMBARGOED FOR RELEASE
Wednesday, September 5, 2007
1:00 p.m. EDT/6:00 p.m. London time
Top: Scanning electron microscopy shows the stair-step pattern of stereocilia. Bottom: Fluorescence microscopy image shows the presence of CDH23 (green) at the point where each short stereocilium (red) meets the side of its taller neighbor.
Credit: B. Kachar, NIDCD
Our ability to hear is made possible by way of a Rube Goldberg-style process in which sound vibrations entering the ear shake and jostle a successive chain of structures until, lo and behold, they are converted into electrical signals that can be interpreted by the brain. Exactly how the electrical signal is generated has been the subject of ongoing research interest.
In a study published in the September 6 issue of the journal Nature, researchers have shed new light on the hearing process by identifying two key proteins that join together at the precise location where energy of motion is turned into electrical impulses. The discovery, described by some scientists as one of the holy grails of the field, was made by researchers at the National Institute on Deafness and Other Communication Disorders (NIDCD), one of the National Institutes of Health (NIH), and the Scripps Research Institute in La Jolla, CA.
“This team has helped solve one of the lingering mysteries of the field,” says James F. Battey, Jr., M.D., Ph.D., director of the NIDCD. “The better we understand the pivotal point at which a person is able to discern sound, the closer we are to developing more precise therapies for treating people with hearing loss, a condition that affects roughly 32.5 million people in the United States alone.”
When a noise occurs, such as a car honking or a person laughing, sound vibrations entering the ear first bounce against the eardrum, causing it to vibrate. This, in turn, causes three bones in the middle ear to vibrate, amplifying the sound. Vibrations from the middle ear set fluid in the inner ear, or cochlea, into motion and a traveling wave to form along a membrane running down its length. Sensory cells (called hair cells) sitting atop the membrane “ride the wave” and in doing so, bump up against an overlying membrane. When this happens, bristly structures protruding from their tops (called stereocilia) deflect, or tilt to one side. The tilting of the stereocilia cause pore-sized channels to open up, ions to rush in, and an electrical signal to be generated that travels to the brain, a process called mechanoelectrical transduction.
Most scientists believe that the channel gates are opened and closed by microscopic bridges—called “tip links”—that connect shorter stereocilia to taller ones positioned behind them. If scientists could determine what the tip links are made of, they’d be one step closer to understanding what causes the channel gates to open. This is no easy feat, however, because stereocilia are extremely small, scarce, and difficult to handle. Several proteins had been reported to occur at the tip link in earlier studies, but results have been conflicting to this point.
Cadherin 23 and Protocadherin 15 Unite to Form Tip Link
Using three lines of evidence, NIDCD scientists Hirofumi Sakaguchi, M.D., Ph.D., Joshua Tokita, and Bechara Kachar, M.D., together with Piotr Kazmierczak and Ulrich Müller, Ph.D., of Scripps Research Institute, and other collaborators have demonstrated that two proteins associated with hearing loss—cadherin 23 (CDH23) and protocadherin 15 (PCDH15)—unite and adhere to one another to form the tip link. Mutations in CDH23 are known to cause one form of Usher syndrome as well as a nonsyndromic recessive form of deafness, and mutations in PCDH15 are responsible for another form of Usher syndrome. (A syndrome is a disease or disorder that has more than one feature or symptom, while the term “nonsyndromic” refers to a disease or disorder that is not associated with other inherited characteristics.) Usher syndrome is the most common cause of deaf-blindness in humans.
“Cadherin 23 and protocadherin 15 have been implicated in a variety of forms of late- and early-onset deafness, and a whole range of mutations can produce different outcomes,” says NIDCD’s Kachar, a co-senior investigator on the study. “Now that we know how these two proteins interact at the tip link, we can perhaps predict how different types of hearing loss can take place depending on where a mutation is located.”
Three Lines of Evidence
The researchers first created antibodies that would bind to and label short segments on the CDH23 and PCDH15 proteins in the inner ears of rats and guinea pigs. (Both proteins were identified at the tip link, respectively, in earlier studies.) Using green fluorescence and electron microscopy studies, they showed that CDH23 was located on the side of the taller stereocilium and PCDH15 was present on the tip of the shorter one, with their loose ends overlapping in between. The researchers were able to identify both proteins, while earlier studies had not, because they removed an obstacle to the antibody-binding process: calcium. Under normal conditions, CDH23 and PCDH15 are studded with calcium ions, which prevent antibodies from binding to the targeted sites. When calcium was removed through the addition of a chemical known as BAPTA, both labels became visible.
Next, the researchers built a structure resembling a tip link by expressing the CDH23 and PCDH15 proteins in the laboratory and watching how they interacted. When conditions were right, the two proteins wound themselves tightly together from one end to the other in a configuration that mirrored a naturally occurring tip link. The results were surprising, since the scientific consensus had been that these proteins would not interact at all. As with normal tip links, the structure thrived in calcium concentrations that paralleled those found in fluid of the inner ear, while a drastic reduction in calcium disrupted the structure.
Lastly, the scientists found that one mutation of PCDH15 that causes one form of deafness inhibited the interaction of the two proteins, leading them to conclude that the mutation reduces the adhesive properties of the two proteins and prevents the formation of the tip link. In a second mutation of PCDH15, the tip link was not destroyed; the scientists suggested that the deafness is not likely caused by the breakup of the tip link but by interference with its mechanical properties.
Knowing precisely the composition and configuration of the tip link, scientists can now explore how these proteins interact with other components to form the rest of the transduction machinery. In addition, scientists can study how new treatments might be developed to address the breaking up of tip links through environmental factors, such as loud noise.
“Now that we understand what the tip link is made of and what conditions are required to assemble it,” says Kachar, “we can study what it might take to rejoin tip links as a possible method for restoring hearing in people with some forms of hearing loss that may have resulted from disruption of the tip link.”
Funding of the study was principally provided by the NIDCD. Other NIH institutes and centers that contributed funding were the National Institute of General Medical Sciences (NIGMS), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and the National Center for Research Resources (NCRR).
The NIDCD supports and conducts research and research training on the normal and disordered processes of hearing, balance, smell, taste, voice, speech, and language and provides health information, based upon scientific discovery, to the public. For more information about NIDCD programs, see the Web site at www.nidcd.nih.gov.
The National Institutes of Health (NIH)—the Nation's Medical Research Agency—includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov. |
<urn:uuid:f9880927-652e-4fa0-bc37-610e3dc3abf3> | seed | |WHO recommendations for the post-pandemic period|
As announced on 10 August, the world is now in the post-pandemic period. Based on knowledge about past pandemics, the H1N1 virus is expected to continue to circulate as a seasonal virus for some years to come. While the level of concern is now greatly diminished, vigilance on the part of national health authorities remains important. Such vigilance is especially critical in the immediate post-pandemic period, when the behaviour of the H1N1 virus as a seasonal virus cannot be reliably predicted.
For example, it is likely that the virus will continue to disproportionately affect a younger age group, at least in the immediate post-pandemic period. Groups identified during the pandemic as at higher risk of severe or fatal illness will probably remain at heightened risk, though the number of such cases could diminish. In addition, a small proportion of people infected during the pandemic developed a severe form of primary viral pneumonia that is not commonly seen during seasonal epidemics and is especially difficult to treat. It is not known whether this pattern will continue during the post-pandemic period, further emphasizing the need for vigilance.
WHO is today issuing guidance on recommended activities during the post-pandemic period, including advice on epidemiological and virological monitoring, vaccination, and the clinical management of cases.
National health authorities are reminded that cases and local outbreaks of H1N1 infection will continue to occur, and in some locations, such outbreaks could have a substantial impact on communities.
WHO recommendations to health authorities during the post-pandemic period
Monitoring of respiratory disease activity
WHO recommends that surveillance during the post-pandemic period include the following activities:
Vaccination remains important as a means of reducing the morbidity and mortality caused by influenza viruses. WHO strongly recommends vaccination of high-risk individuals in countries where influenza vaccines are available.
Protection against the H1N1 2009 virus can be conferred through either the monovalent (single virus) pandemic H1N1 2009 vaccines or the current trivalent seasonal influenza vaccines. The trivalent seasonal vaccines now contain the H1N1 2009 virus, which replaces the pre-pandemic H1 strain that is no longer circulating, as well as H3 and B circulating seasonal influenza strains.
Persons suspected of illness from influenza should receive appropriate clinical care. WHO's guidelines for clinical management, which refer to both seasonal and pandemic influenza, offer guidance . The H1N1 virus is expected to continue to circulate as a seasonal virus for some years to come. Cases of severe illness in higher-risk individuals, as well as in otherwise healthy individuals, are likely to occur. Early recognition and appropriate treatment of such cases remains important. WHO's guidelines for use of antiviral medicines, which refer to both seasonal and pandemic influenza, should continue to be followed.
Groups at increased risk of severe illness from the pandemic H1N1 virus included young children, pregnant women, and people with underlying respiratory or other chronic conditions, including asthma and diabetes. Patients who have severe or deteriorating influenza should be treated as soon as possible with oseltamivir. Patients who are at higher risk of severe or complicated influenza should be treated with oseltamivir or zanamivir as soon as possible.
Regional Office for the Americas of the World Health Organization |
<urn:uuid:74c04176-ed9f-435e-bad7-b79c0774b8f0> | seed | Microscopic examination of tumor specimens cannot always predict a cancer's aggressiveness, leading to increased interest in molecular approaches to diagnosis. Now, researchers in the Children's Hospital Informatics Program (CHIP) at the Harvard-MIT Division of Health Sciences and Technology report that a genetic profile indicating chromosomal instability -- an increased tendency to develop chromosomal aberrations, critical in cancer development -- is predictive of clinical outcome in a broad range of cancer types.
Using data on gene expression (activity) from 18 previous studies of cancer, representing six cancer types, they found that this genetic profile, or signature, predicted poor clinical outcome in 12 of the populations studied. The study was published online by the journal Nature Genetics on August 20.
"Chromosomal instability is one of the key mechanisms that keeps malignant cell proliferation going," says Zoltan Szallasi, MD, a CHIP researcher and the study's senior investigator. "We have achieved a relatively easy way to measure the level of chromosomal instability in a given tumor sample."
The technique may help in the search for cancer drugs that reduce chromosomal instability -- an approach of increasing interest to researchers -- by making it possible to screen a large number of drugs for efficacy, Szallasi notes. With further development, the team's work could also form the basis of a diagnostic tool that could be used in the clinic.
The human genome is at constant risk for mutations due to environmental insults, errors in gene replication, and other factors that can cause chromosomes to break and bits of DNA to be lost, duplicated or reshuffled to the wrong chromosomes. Cells have repair mechanisms that constantly fix this damage, but when the repair process breaks down, chromosomes become unstable and cancers are more likely to develop.
Chromosomal instability leads to a condition known as aneuploidy, in which chunks of DNA are either missing or duplicated. The technique developed by Szallasi's team indirectly measures the degree of aneuploidy -- and thus the degree of chromosomal instability -- by looking for abnormal expression levels of genes at the different chromosomal locations.
Next, the researchers identified 25 genes whose activity most strongly predicted chromosomal instability itself. This 25-gene signature was a significant predictor of clinical outcomes in a variety of cancers (breast, lung, medulloblastoma, glioma, mesothelioma and lymphoma). It could also differentiate between primary tumors and tumor metastases, and, in grade 1 and grade 2 breast cancer, distinguished the more aggressive cancers within each grade.
The study was supported by grants from the National Institutes of Health and the Department of Defense.
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<urn:uuid:88e78a4b-5aef-4931-8de8-e44ba2ebebc9> | seed | March 28, 2013
Genetic Markers For Smoking May Help Predict Who Gets Hooked
Brett Smith for redOrbit.com - Your Universe Online
According to a new study in JAMA Psychiatry, a team of international scientists has developed a genetic profile that indicates a greater risk for a teenager's progression into becoming a lifelong heavy smoker.
People who share the genetic profile showed a greater risk of daily smoking as teenagers and then progressing more rapidly to smoking a pack a day or more as adults, the study said. High-risk individuals who were assessed in their late thirties were found to have smoked heavily for more years, have a greater nicotine dependence and were more likely to have multiple failed in attempts to quit smoking.
"Genetic risk accelerated the development of smoking behavior," said study co-author Daniel Belsky, a post-doctoral research fellow at Duke University. "Teens at a high genetic risk transitioned quickly from trying cigarettes to becoming regular, heavy smokers."
The research team began by looking at earlier studies to identify genetic signifiers of heavy smokers. In particular, they examined their own 38-year study of 1,000 New Zealanders to identify whether individuals at high genetic risk picked up a smoking habit more quickly as teens and if they had a more difficult time quitting as adults.
In order to rank individuals, the researchers developed a "genetic risk score" based on prior genome-wide associations of adult smokers. After identifying the genetic variants most common to heavy smokers, the team noted that these variants affect how the brain and body respond to nicotine. However, they were unable to determine how the specific variants affect the particular gene where they are located.
After identifying the genetic variants, the team examined the data culled from their New Zealand study to see if an individual´s genetic risk score could predict things like who began smoking, who progressed to heavy smoking, who became addicted and who experienced relapse after attempting to quit.
The researchers found that genetic risk factors were not associated to whether a person tried smoking, as 70 percent of all participants had. One group of non-addicted smokers emerged in the study — the so-called "chippers" — who smoke once or twice a day or at social gathering. These individuals showed an even lower genetic risk than nonsmokers.
The analysis showed that teens with a high-risk genetic profile who tried cigarettes were 24 percent more likely to become daily smokers by age 15 and 43 percent more likely to average a pack-a-day or more by age 18.
As adults, these high-risk individuals were 27 percent more likely to become nicotine addicts and 22 percent more likely to fail at quitting.
"The effects of genetic risk seem to be limited to people who start smoking as teens," said Belsky. "This suggests there may be something special about nicotine exposure in the adolescent brain, with respect to these genetic variants."
"Adolescence is indeed a period of high risk for nicotine addiction," said Denise Kandel, a professor of sociomedical sciences in psychiatry at Columbia University, who was not involved in this study.
"The results illustrate why adolescence is of crucial importance for the development and targeting of prevention and intervention efforts. How this genetic risk affects brain functions, which in turn affect reactions to nicotine, remains to be determined."
"Public health policies that make it harder for teens to become regular smokers should continue to be a focus in antismoking efforts," Belsky said. |
<urn:uuid:8322fa32-8b18-4bc1-b0a0-0eee422a32ba> | seed | From MicrobeWiki, the student-edited microbiology resource
A Microbial Biorealm page on the genus Yersinia
Higher order taxa:
Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacteriales; Enterobacteriaceae
Yersinia pestis CO92, Y. pestis, Y. enterocolitica, Y. pseudotuberculosis
Description and Significance
Yersinia spp. are responsible for disease syndromes ranging from gastroenteritis to plague. Y. pestis is the cause of the plague and is actually catagorized into three subtypes or biovars; Antiqua, Medievalis, and Orientalis, each associated with a major pandemic. Y. pestis strand KIM belongs to biovar Mediaevalis while strand CO92 is in biovar Orientalis. Biovar Mediaevalis is thought to of descended from the bacteria that caused the second pandemic (the Black Death), while biovar Orientalis bacteria are responsible for the current pandemic (modern plague).
It is believed that Y. pestis is a clone that evolved from Y. pseudotuberculosis about 1.5 to 20 thousand years ago. This means that Y. pestis has evolved rapidly from being a pathogen widely found in the environment, able to infect mammalian intestines, to a blood-borne pathogen of mammals that can parasitize insects and has a limited capacity for survival outside a host.
Y. pestis CO92 has a circular chromosome that is 4.65Mb in size with three plasmids pMT1 (96.2kb), pPCP1 (9.6kb), and pCD1 (70.3kb). The other Y. pestis strain sequenced, strain KIM, has the same three plasmids as well as a circular chromosome, but is 50kb smaller with 4.6Mb. When the two genomes were compared, a lot of similarity was found. The genomes share more than 95% of their sequence and 3,672 of 4,198 total ORFs match. Strain CO92 has one less rRNA operon than KIM.
Cell Structure and Metabolism
Y. pestis is rod shaped, gram negative, and non-motile yet has two distinct flagellar gene clusters; one set is incomplete and the other has a truncated FldH, which is a transcriptional activator for the flagellar genes.
Y. pestis uses aerobic respiration and anaerobic fermentation to produce and consume hydrogen gas for energy.
Yersinia species are pathogens whose environments are not rich in minerals and grow at temperatures ranging from about 26oC to 37oC.
Y. pseudotuberculosis and Y. enterocolitica both infect the intestines of mammals through the fecal-oral route (contaminated food and water) and rarely is deadly. Y. pestis, on the other hand, is transmitted subcutaneously through a bite of an infected flea or rat (bubonic), but can also be transmitted by air (especially during pandemics of the disease). More specifically, fleas become infected after taking blood meals from septicemic animals and becoming infected themselves. Y. pestis grows in the midgut and eventually blocks the proventriculus, starving the flea for blood. The insects attempt to feed more often but end up giving back infected blood into the wound of the bite. The flea eventually dies, presumably from starvation and dehydration. On an interesting note, when the temperatures get higher fleas do not have their proventriculus blocked, and only those that are blocked can transmit the disease. When held at 30oC, fleas survive infections in an unblocked state, possibly leading at an explanation of why human bubonic plagues ended after the onset of warmer temperatures.
All pathogenic species of Yersinia contain the pCD1virulence plasmid. Y. pestis obtained two unique plasmids that encode a variety of virulence determinants. The pPCP1 plasmid encodes the plasminogen activator Pla, essential for virulence through the subcutaneous route. The pMT1 plasmid encodes murine toxin Ymt and the F1 capsular protein, which have been shown to play a role in the transmission of plague. Ymt, designated murine toxin because the protein is highly lethal for mice, is required for Y. pestis to survive in fleas. Ymt mutants, however, are as virulent as its parent in mice with plague.
Researchers have also discovered that at rising temperatures cells gradually lose their ability to bind Congo red (CR) along with their ability to cause disease in mice from peripheral routes of infection. This is because in the pgm (pigmentation) operon there are genes encoding the yersiniabactin (Ybt) siderophore-dependent iron transport system, required for virulence in mice subcutaneously, as well as genes for the Hms phenotype, which is required for cells to colonize and block the proventriculus.. A pgm deletion is therefore lethal to Y. pestis.
Parkhill et al. 2001. Genome sequence of Yersinia pestis, the causative agent of plague. Nature 413: 523-527. [Abstract]
Deng et al. 2002. Genome Sequence of Yersinia pestis KIM. Journal of Bacteriology 184 16: 4601-4611.
Achtman et al. 1999. Yersinia pestis, the cause of plague, is a recently emerged clone of Yersinia pseudotuberculosis. PNAS 96 24: 14043-14048.
Pepe, Jeffrey C. and Virginia L. Miller. 1993. Yersinia enterocoliticainvasion: A primary role in the initiation of infection. PNAS 90: 6473-6477.
Perry, Robert D. 2003. A Plague of Fleas - Survival and Transmission of Yersinia pestis. ASM News 69 7: 336-340. |
<urn:uuid:1b354558-1200-4c97-8f91-5a60b9eab1bf> | seed | Am Fam Physician. 2005 May 1;71(9):1808-1810.
Osteoporosis is increasing in prevalence as the population ages. However, it is unlikely that women at risk for osteoporosis are being screened according to recommendations. Furthermore, it may be that screening guidelines are not presenting a unified message to physicians and patients as to who should be screened. Morris and colleagues performed a structured review to determine whether the existing guidelines offer sufficient clarity regarding screening recommendations, and whether patient risk factors adequately define who should be screened. They also sought to determine whether effective strategies exist for improving screening rates.
Data were abstracted from clinical guidelines, articles on rates and predictors of bone mineral density (BMD) testing, and articles on interventions to increase testing rates. Of the 17 practice guidelines included in the review, almost one third did not provide information on how the guidelines were established, and more than one half gave no definition of “consensus.” Explanations of how evidence was graded and considerations of cost also were lacking in many of the guidelines. Ten of the guidelines were developed with pharmaceutical industry support. The guidelines were inconsistent about the age at which women should be screened and the risk factors that should be considered.
Articles on rates of BMD testing often focused on patients taking steroid medications or those with previously sustained fractures. In these, reports of testing rates varied widely. There were few consistent patient or physician characteristics that predicted BMD testing. Two studies showed that female patients and those under the care of a rheumatologist were more likely to undergo BMD testing. In terms of physician characteristics, being female and having a large postmenopausal patient population were associated with higher testing rates.
One trial of an intervention to improve testing rates found that counseling patients with a positive rather than negative focus was more likely to lead to BMD testing. Another study showed that longer narrative reports on BMD testing results led to higher physician testing rates than short technical reports.
In summary, the authors found that screening guidelines were lacking in uniform recommendations, that screening rates generally were low, and that few interventions to improve screening rates have been studied. Predictors of testing also have not been studied sufficiently, making it difficult to determine whether testing is being carried out on the appropriate patients. Furthermore, even if the criteria for testing were clearly defined, it is unclear what interventions could be used to improve screening rates.
Morris CA, et al. Patterns of bone mineral density testing. J Gen Intern Med. July 2004;19:783–90.
Copyright © 2005 by the American Academy of Family Physicians.
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<urn:uuid:b27059b5-fcde-4142-8b9c-4c7350390d6e> | seed | Both types of tea block cell-poisoning effects of plaque-forming amyloid protein
by Craig Weatherby
It seems that tea may fit brain health to a "T".
As we reported last month, the results of a Japanese study in people aged 70 or older suggest that green tea may reduce the risk of mental decline (Kuriyama S, 2006), with the lowest risk of mental decline being associated with drinking at least two cups of green tea per day (See “Tea May Combat Women’s Cancers and Help Keep Seniors Mentally Sharp”).
Hard on the heels of those findings come new research results from Canada, which suggest that the image of the spry, tea-drinking septuagenarian—or even nonagenarian—with a twinkle in his or her eye may be more than a wishful, sentimental representation.
The study was performed in rat cells from the hippocampus—a part of the brain key to rodent and human memory—suggests that both black and green tea may be equally powerful allies against the cell-killing protein plaque associated with Alzheimer’s disease (AD).
Results that the Canadian team reported (Bastianetto S, 2006) confirm that compounds in green and black tea can block the toxic effects of amyloid proteins, which form the brain-coating plaques characteristic of Alzheimer’s disease.
And this study—performed by Rémi Quirion, Ph.D. and colleagues at Quebec’s Douglas Hospital Research Centre—is not the first whose results suggest that tea flavanols can protect against amyloid toxicity.
A study in human brain cells (Levites Y 2003) showed that tea flavanols can protect against amyloid toxicity, and do it in the kind of dose-dependent manner that further confirms the reality of the effect.
Black tea equals green for brain-protecting power
The compounds found to cut the toxic effects of amyloid proteins are the same flavanols associated with tea’s anti-cancer and heart-health properties.
While green tea contains more of the three flavanol antioxidants that showed the greatest protective power—gallic acid (GA), epicatechin gallate (ECG), and epigallocatechin gallate (EGCG)—exposure to identical amounts of black or green tea extract produced the same protective effects.
This equity of effect was something of a surprise, since black tea contains only half as much of these specific flavanol antioxidants, compared with green tea.
To make black tea, green tea leaves are crushed and heated to promote fermentation: a process that results in oxidation of a portion of their flavanols. Oxidation polymerizes (links together in chains) a portion of the fresh leaves’ flavanols, creating new compounds called theaflavins and even larger flavanol chains called thearubigens, which give black tea its characteristic astringency, briskness, and bright, reddish-brown colors.
(We should note that white tea is the richest source of the amyloid-busting flavanols—GA, ECG, and EGCG—because while green tea is slightly fermented/oxidized and black tea is heavily fermented/oxidized, white tea is almost completely unfermented/oxidized.)
But, despite its reduced flavanol content versus green tea, black tea extract appears to exert just as powerful a protective effect against amyloid proteins, at least in isolated rat brain cells.
The protective effects took two forms:
- EGCG and GA kept amyloid proteins from aggregating, which could result in plaque formation.
- EGCG and GA stopped formation of potentially toxic amyloid derivatives that can pass through cell membranes.
Want to stay mentally sharp? These discoveries indicate that you may be able to preserve mental acuity longer by drinking the tea of your choice, green or black.
- Kuriyama S, Hozawa A, Ohmori K, Shimazu T, Matsui T, Ebihara S, Awata S, Nagatomi R, Arai H, Tsuji I. Green tea consumption and cognitive function: a cross-sectional study from the Tsurugaya Project 1. Am J Clin Nutr. 2006 Feb;83(2):355-61.
- Bastianetto S, Yao ZX, Papadopoulos V, Quirion R. Neuroprotective effects of green and black teas and their catechin gallate esters against beta-amyloid-induced toxicity. Eur J Neurosci. 2006 Jan;23(1):55-64.
- Levites Y, Amit T, Mandel S, Youdim MB. Neuroprotection and neurorescue against Abeta toxicity and PKC-dependent release of nonamyloidogenic soluble precursor protein by green tea polyphenol (-)-epigallocatechin-3-gallate. FASEB J. 2003 May;17(8):952-4. Epub 2003 Mar 28. |
<urn:uuid:daaec7bc-95d9-4845-b7d4-5ed3f03eba97> | seed | Prolonged gestation associated with fetal deformity cases usually occur as the result of some compromise of the hypothalamic-pituitary-adrenal axis of the fetus, which is no longer able to initiate parturition. The affected fetus may either die and be aborted or live on indefinitely in the uterus. Genetic, infectious, toxic, and unknown causes have been associated with this problem.
Prolonged gestation associated with fetal adrenal malfunction is a genetically determined prolonged gestation caused by an autosomal recessive gene of the fetus in Holstein-Friesian cows. The fetal adrenal glands fail to produce corticosteroids at term, in response to fetal ACTH. As a result, the fetus continues to grow until it outgrows its blood supply. Induction with dexamethasone does not induce normal labor and parturition because of insufficient preparation of the birth canal. A cesarean section will save the dam, but the fetus invariably dies due to adrenal insufficiency.
Four further genetic abnormalities associated with prolonged gestation in various breeds of cattle involve fetal pituitary abnormalities. In one condition, severe fetal oversize (fetal giantism) is present. In the second, the calf has severe craniofacial defects and is much smaller than normal. In the third condition, multiple skeletal abnormalities are present. In a fourth condition, genetic abnormalities may occur as a result of cloning.
Prolonged gestation and fetal giantism has been reported in Holstein-Friesian, Ayrshire, and Swedish breeds of cattle. Gestation is prolonged by 21–150 days. Pronounced abdominal enlargement is seen in some cases. There is no attempted parturition unless the fetus dies first after having outgrown its blood supply. Cervical relaxation is poor, and dystocia invariably results. The calf weighs 48–80 kg at birth and shows signs of postmaturity. The coat and hooves are longer than normal, and prominent loose teeth are present in the gums. Breathing is difficult as a result of failure of surfactant release, and the calf may die from hypoglycemia. At necropsy, hypoplasia of the anterior pituitary and adrenal glands is seen.
Prolonged gestation with craniofacial defects in the fetus has been reported in Holstein-Friesian, Ayrshire, Guernsey, and Jersey breeds of cattle and is thought to be caused by a recessive gene. Affected fetuses cease to grow at 7 mo gestation. There is no spontaneous parturition in affected cattle because of the nonfunctional or absent pituitary gland in the fetus. Calves are usually dead when delivered. Some may show evidence of severe abnormalities of the cranium and face.
Prolonged gestation associated with multiple skeletal abnormalities has been reported in Hereford cattle. Affected calves show evidence of pituitary aplasia or hypoplasia. Arthrogryposis, torticollis, kyphosis, and scoliosis are present, and some calves have cleft palates.
Prolonged gestation associated with cloning has been reported in both fetal calves and lambs produced by somatic cell nuclear cloning. Early placental abnormalities have been detected in a high proportion of such animals, and placentomegaly may be seen in later pregnancy. The abnormality may result in fetal death or, if the fetus survives, in the large offspring syndrome. Spontaneous birth may not occur, and prolonged gestation results. Fetal lung and maternal mammary development is retarded and can compromise fetal survival.
Although bovine viral diarrhea virus (see Bovine Viral Diarrhea and Mucosal Disease Complex) can cause abortion in cattle, it can also produce congenital defects in the fetus. These include cerebellar hypoplasia, anencephaly, and hydrocephaly. Affected calves may be born with severe defects of the CNS, but prolonged gestation occasionally occurs if pituitary function is compromised. The related pestivirus border disease virus (see Border Disease) can produce severe brain and coat abnormalities in fetal lambs. Pituitary compromise in such lambs can lead to prolonged gestation.
Akabane virus (see Akabane Virus Infection), found in Africa, Australia, the Middle East, and the Far East, can be transmitted by insects to both pregnant cattle and sheep. Bovine fetuses exposed to the virus at 76–104 days gestation may develop hydranencephaly (fluid-filled cavitation of the brain). Exposure to the virus at 105–174 days of pregnancy may cause both hydranencephaly and arthrogryposis. Affected fetuses may have severe brain damage. The cerebral cortex may be absent and the cranial cavity filled with fluid. Cerebellar hypoplasia may be present, and the brain stem is smaller than normal. Compromise of pituitary function in the affected fetus can lead to prolonged gestation.
Bluetongue virus (see Bluetongue), found in Africa, Australia, North and South America, and Europe, is also transmitted by insects; infection can occasionally cause prolonged gestation. The fetuses of cows exposed to the virus at 60–120 days of pregnancy developed hydranencephaly, whereas fetuses exposed later in pregnancy developed less severe CNS defects.
Gestation lengths >200 days have been recorded in ewes vaccinated during pregnancy with Rift Valley fever attenuated viral vaccine. Affected lambs developed severe brain defects and skeletal abnormalities. Some ewes developed hydrops amnion by the fourth month of gestation. Ewes in which pregnancy was not terminated developed ketosis.
Several plant toxins cause fetal deformity and prolonged gestation when eaten accidentally or fed experimentally. When fed to sheep in early pregnancy, Veratrum californicum (skunk cabbage) produces fetal deformities, giantism, and prolonged gestation. Cranial defects and brain and eye abnormalities were seen in fetuses of ewes fed this plant at 14 days of gestation; pregnancy length in some cases was >230 days. The plant contains the amine cyclopamine, which is believed to be responsible for the fetal abnormalities. This plant also contains a number of toxic alkaloids that cause GI disturbance, dyspnea, and convulsions in sheep. Veratrum album has similarly caused prolonged gestation and fetal abnormalities in Holstein-Friesian cows in Japan.
An unidentified toxin in the plant Salsola tuberculatiformis (cauliflower saltwort) is thought to cause prolonged gestation in sheep. Pregnancy was extended >220 days, and affected lambs showed atrophy of the pituitary, adrenal, and thyroid glands. Fetuses appear to be most susceptible to the toxin in the first and third trimesters of pregnancy. Amniotic fluid continues to increase in volume in cases of prolonged gestation associated with this plant. Physical abnormalities such as cleft palate prevent normal swallowing of amniotic fluid in affected fetuses. Excessive fetal weight and the weight of accumulated fetal fluids may lead to rupture of the prepubic tendon in ewes.
Last full review/revision December 2013 by Peter G. G. Jackson, MA, BVM&S, DVM&S, FRCVS |
<urn:uuid:707229b4-9ef7-41e1-87c1-282c309e7da5> | seed | Decoding your DNA: it's becoming easier to unravel a person's entire genetic code. What will this information reveal about you?
Back in 1990, biologists began an epic task. They set out to decode the entire human genome--the blueprint of life encoded in molecules of DNA. DNA is the hereditary material found in every one of our cells. The Human Genome Project cost $3 billion and took more than a decade for scientists to complete.
Although the project was a great success, science has come a long way since then. Now, a machine about the size of a computer printer can sequence, or translate, a person's genome in a single day for an estimated $1,000.
Your genome is like your own personal instruction manual: It carries the directions that determine almost everything about you, from the color of your eyes to your blood type. With access to your complete genetic code, you can learn about not only these types of traits, but also about your ancestry--and, perhaps most important, your health.
"Today, sequencing is being used to better understand diseases, their treatment, and their prevention," says Bob Fulton, a molecular biologist at the Genome Institute at Washington University in St. Louis, Mkssouri.
CRACKING THE CODE
DNA is made up of four building blocks called bases: adenine (A), thymine (T), guanine (G), and cytosine (C). A molecule of DNA looks like a twisted ladder (see The Human Genome, right). The ladder's rungs are the bases from each of the ladder's strands, or sides, that have paired up--A always with T and G always with C.
Sequencing a person's genetic code means figuring out the order of the 3 billion bases along one of the strands. Written out, a chunk of a translated genome would look something like this: ACGACTTAAGTAGTACATG. An entire human genome contains enough letters to fill roughly 400 paperback books, each 500 pages long (see Size Comparison, p. 22).
Within a genome's sequence are sections that form genes. Genes carry the directions to make proteins. These molecules have many jobs in the body. Proteins guide how cells function and ultimately determine a person's different traits. It's estimated that humans have about 25,000 genes.
Sometimes mistakes can crop up in the DNA sequence that codes for a gene. These errors are called mutations. Single altered genes cause some illnesses, like the lung disease cystic fibrosis. But others, like diabetes, are the result of multiple mutated genes working together--along with factors like diet, lifestyle, and the environment.
For the most part, people's genetic codes are pretty similar. "Between any two individuals, about one in 1,000 bases will be different," says Fulton. He and other scientists use genome sequencing to compare the genetic codes of people who have a certain disease with those who don't. Where the genomes vary could indicate a mutation linked to that disease.
CHEAPER AND FASTER
Sequencing a person's complete genome for $1,000 had long been a goal for scientists. "It puts genome sequencing within the price range of other standard hospital-based diagnostic tests, like an MRI or a CT scan," says Andy Felton, a chemist and director of marketing for the company Ion Torrent. This year, Ion Torrent launched the first sequencing machine that hit the $1,000 target. It can sequence a human genome quickly and affordably, thanks to a tiny microchip.
HOW SEQUENCING WORKS
To sequence a person's DNA, its two strands are separated. One strand is then cut into short pieces. Each fragment goes into one of 660 million wells on the microchip's surface. Inside the machine, the chip gets washed with solutions of different bases. These bases match up with their complementary bases on the DNA fragments. This causes a chemical reaction that the chip detects, allowing it to record the position of the bases.
Once the DNA fragments have been sequenced, a computer re-creates the genome. "It's like a giant jigsaw puzzle that you have to put back together," says Felton.
There's still a long way to go before genome sequencing becomes a routine part of a doctor visit. But someday, sequencing could allow physicians to customize health care to fit each patient.
From a person's genetic code, a doctor could learn what diseases the patient is at risk for and take measures to help him or her avoid getting sick. Since genes are inherited, physicians could screen patients' genomes for genetic diseases that might be passed on to their children.
Genes can even affect how a person responds to certain medications. Sequencing could help a doctor figure out the most effective prescription to give a patient.
RISKS VS. BENEFITS
Is there a downside to having your genome sequenced? Some people may not want to know if they have a high risk of developing a condition that is currently untreatable. Others worry about whether their genetic information could be used against them. This concern prompted Congress to pass the Genetic Information Nondiscrimination Act in 2008. It protects people from things like being denied insurance coverage or being fired based on their genes.
Right now, scientists are studying the human genome to figure out how to best help people use the wealth of information it contains. "There's endless work to be done yet," says Fulton. But he predicts that within your lifetime, decoding people's genetic codes will be commonplace. "The cheaper DNA sequencing gets," he says, "the more readily available it becomes for everyone to have their genome sequenced."
THE HUMAN GENOME: YOUR INSTRUCTION MANUAL
CELLS: The human body contains trillions of cells, the basic units of life.
CHROMOSOMES: Packed inside the nucleus, or center, of each cell are 46 structures called chromosomes.
DNA: Each chromosome contains a long, tightly coiled molecule of DNA, a person's hereditary material.
BASES: DNA is made up of a sequence of four bases, abbreviated A, G, T, and C. Bases on one side of a DNA molecule pair up with partners on the other side: A always with T and G always with C.
GENES: Series of bases are organized into genes, which carry the instructions to make proteins. Proteins keep cells functioning and determine a person's traits.
GENES AND DISEASE
Sometimes "spelling mistakes" can occur within the bases that make up a gene's DNA sequence. These errors are called mutations, and they can affect the function of that gene.
Scientists have found about 6,000 diseases caused by mutations in single genes by studying people's genomes. A genome is a person's complete set of DNA. They are still working to learn how combinations of genetic mutations, along with diet, lifestyle, and the environment, can lead to illnesses.
Species' genomes vary in size. But just because a species is small doesn't mean its genome is too. A single-celled amoeba has the largest known genome, at 670 billion bases long. Compare that with humans'.
WHAT DO YOU THINK?
Would you choose to have your genome sequenced to screen for diseases? Explain why or why not. |
<urn:uuid:b77016e3-03ec-407b-a490-c0d8f17f3986> | seed | The Lancet iPad application (app) spans across all Lancet titles including The Lancet, The Lancet Oncology,
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The British Health Protection Agency has confirmed five patients with oseltamivir-resistant pandemic influenza A(H1N1) virus on a hospital ward in Wales.
“Although further epidemiological investigation is underway, it would seem likely that transmission of oseltamivir-resistant H1N1 virus has taken place,” the Health Protection Agency said in a written statement Nov. 20.
A total of nine patients on that hospital ward have confirmed H1N1 influenza. One of those patients has virus that is sensitive to oseltamivir, and the resistance status of the remaining three is not yet known.
Oseltamivir is one of two antiviral drugs approved to treat H1N1 virus. The oseltamivir-resistant patients appear to be responding well to treatment with the other frontline drug, called zanamivir, the statement said.
The oseltamivir-resistant patients all have hematologic problems that result in immunosuppression either because of their disorder or because of the chemotherapy used to treat it. Oseltamivir resistance to other influenza viruses is well documented and can arise quickly, according to the HPA’s statement.
The statement also said that as of Nov. 20 the World Health Organization has reported a total of 57 cases of oseltamivir resistance around the world, although no person-to-person transmission has been documented. However, on Nov. 19, U.S. authorities informed the WHO of four patients in the same hospital who are oseltamivir-resistant and have H1N1. The cases were at Duke University Medical Center, public health officials in North Carolina said.
“Generally, the pandemic H1N1 oseltamivir-resistant viruses are not considered ‘fit’ and transmission is poor,” the HPA said.
Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed. |
<urn:uuid:1f847c5f-15c4-4fbd-ab5f-26a2ca68f986> | seed | Approach to the Patient
History: History is of critical diagnostic importance. Physical exam may be unrevealing or misleading, and laboratory and radiologic exams delayed or unhelpful.
CHARACTERISTIC FEATURES OF ABDOMINAL PAIN
Duration and Pattern: These provide clues to nature and severity, although acute abdominal crisis may occasionally present insidiously or on a background of chronic pain.
Type and location provide a rough guide to nature of disease. Visceral pain (due to distention of a hollow viscus) localizes poorly and is often perceived in the midline. Intestinal pain tends to be crampy; when originating proximal to the ileocecal valve, it usually localizes above and around the umbilicus. Pain of colonic origin is perceived in the hypogastrium and lower quadrants. Pain from biliary or ureteral obstruction often causes pts to writhe in discomfort. Somatic pain (due to peritoneal inflammation) is usually sharper and more precisely localized to the diseased region (e.g., acute appendicitis; capsular distention of liver, kidney, or spleen), exacerbated by movement, causing pts to remain still. Pattern of radiation may be helpful: right shoulder (hepatobiliary origin), left shoulder (splenic), midback (pancreatic), flank (proximal urinary tract), groin (genital or distal urinary tract).
Factors that precipitate or relieve pain: Ask about its relationship to eating (e.g., upper GI, biliary, pancreatic, ischemic bowel disease), defecation (colorectal), urination (genitourinary or colorectal), respiratory (pleuropulmonary, hepatobiliary), position (pancreatic, gastroesophageal reflux, musculoskeletal), menstrual cycle/menarche (tuboovarian, endometrial, including endometriosis), exertion (coronary/intestinal ischemia, musculoskeletal), medication or specific foods (motility disorders, food intolerance, gastroesophageal reflux, porphyria, adrenal insufficiency, ketoacidosis, toxins), and stress (motility disorders, nonulcer dyspepsia, irritable bowel syndrome).
Associated symptoms: Look for fevers/chills (infection, inflammatory disease, infarction), weight loss (tumor, inflammatory disease, malabsorption, ischemia), nausea/vomiting (obstruction, infection, inflammatory disease, metabolic disease), dysphagia/odynophagia (esophageal), early satiety (gastric), hematemesis (esophageal, gastric, duodenal), constipation (colorectal, perianal, genitourinary), jaundice (hepatobiliary, hemolytic), diarrhea (inflammatory disease, infection, malabsorption, secretory tumors, ischemia, genitourinary), dysuria/hematuria/vaginal or penile discharge (genitourinary), hematochezia (colorectal or, rarely, urinary), skin/joint/eye disorders (inflammatory disease, bacterial or viral infection).
Predisposing factors: Inquire about family history (inflammatory disease, tumors, pancreatitis), hypertension and atherosclerotic disease (ischemia), diabetes mellitus (motility disorders, ketoacidosis), connective tissue disease (motility disorders, serositis), depression (motility disorders, tumors), smoking (ischemia), recent smoking cessation (inflammatory disease), ethanol use (motility disorders, hepatobiliary, pancreatic, gastritis, peptic ulcer disease).
Physical examination: Evaluate abdomen for prior trauma or surgery, current trauma; abdominal distention, fluid, or air; direct, rebound, and referred tenderness; liver and spleen size; masses, bruits, altered bowel sounds, hernias, arterial masses. Rectal examination assesses presence and location of tenderness, masses, blood (gross or occult). Pelvic examination in women is essential. General examination: evaluate for evidence of hemodynamic instability, acid-base disturbances, nutritional deficiency, coagulopathy, arterial occlusive disease, stigmata of liver disease, cardiac dysfunction, lymphadenopathy, and skin lesions.
Routine laboratory and radiologic studies: Choices depend on clinical setting (esp. severity of pain, rapidity of onset) and may include complete blood count, serum electrolytes, coagulation parameters, serum glucose, and biochemical tests of liver, kidney, and pancreatic function; chest x-ray to determine the presence of diseases involving heart, lung, mediastinum, and pleura; electrocardiogram is helpful to exclude referred pain from cardiac disease; plain abdominal radiographs to evaluate bowel displacement, intestinal distention, fluid and gas pattern, free peritoneal air, liver size, and abdominal calcifications (e.g., gallstones, renal stones, chronic pancreatitis).
Special studies: These include abdominal ultrasonography (to visualize biliary ducts, gallbladder, liver, pancreas, and kidneys); CT to identify masses, abscesses, evidence of inflammation (bowel wall thickening, mesenteric “stranding,” lymphadenopathy), aortic aneurysm; barium contrast radiographs (barium swallow, upper GI series, small-bowel follow-through, barium enema); upper GI endoscopy, sigmoidoscopy, or colonoscopy; cholangiography (endoscopic, percutaneous, or via MRI), angiography (direct or via CT or MRI), and radionuclide scanning. In selected cases, percutaneous biopsy, laparoscopy, and exploratory laparotomy may be required.
Numerous causes, ranging from acute, life-threatening emergencies to chronic functional disease and disorders of several organ systems, can generate abdominal pain. Evaluation of acute pain requires rapid assessment of likely causes and early initiation of appropriate therapy. A more detailed and time-consuming approach to diagnosis may be followed in less acute situations. Table 43-1 lists the common causes of abdominal pain.
TABLE 43-1 COMMON ETIOLOGIES OF ABDOMINAL PAIN
Mucosal or muscle inflammation in hollow viscera: Peptic disease (ulcers, erosions, inflammation), hemorrhagic gastritis, gastroesophageal reflux, appendicitis, diverticulitis, cholecystitis, cholangitis, inflammatory bowel diseases (Crohn's, ulcerative colitis), infectious gastroenteritis, mesenteric lymphadenitis, colitis, cystitis, or pyelonephritis
Visceral spasm or distention: Intestinal obstruction (adhesions, tumor, intussusception), appendiceal obstruction with appendicitis, strangulation of hernia, irritable bowel syndrome (muscle hypertrophy and spasm), acute biliary obstruction, pancreatic ductal obstruction (chronic pancreatitis, stone), ureteral obstruction (kidney stone, blood clot), fallopian tubes (tubal pregnancy)
Vascular disorders: Mesenteric thromboembolic disease (arterial or venous), arterial dissection or rupture (e.g., aortic aneurysm), occlusion from external pressure or torsion (e.g., volvulus, hernia, tumor, adhesions, intussusception), hemoglobinopathy (esp. sickle cell disease)
Distention or inflammation of visceral surfaces: Hepatic capsule (hepatitis, hemorrhage, tumor, Budd-Chiari syndrome, Fitz-Hugh-Curtis syndrome), renal capsule (tumor, infection, infarction, venous occlusion), splenic capsule (hemorrhage, abscess, infarction), pancreas (pancreatitis, pseudocyst, abscess, tumor), ovary (hemorrhage into cyst, ectopic pregnancy, abscess)
Peritoneal inflammation: Bacterial infection (perforated viscus, pelvic inflammatory disease, infected ascites), intestinal infarction, chemical irritation, pancreatitis, perforated viscus (esp. stomach and duodenum), reactive inflammation (neighboring abscess, incl. diverticulitis, pleuropulmonary infection or inflammation), serositis (collagen-vascular diseases, familial Mediterranean fever), ovulation (mittelschmerz).
Abdominal wall disorders: Trauma, hernias, muscle inflammation or infection, hematoma (trauma, anticoagulant therapy), traction from mesentery (e.g., adhesions)
Toxins: Lead poisoning, black widow spider bite
Metabolic disorders: Uremia, ketoacidosis (diabetic, alcoholic), Addisonian crisis, porphyria, angioedema (C1 esterase deficiency), narcotic withdrawal
Neurologic disorders: Herpes zoster, tabes dorsalis, causalgia, compression or inflammation of spinal roots, (e.g., arthritis, herniated disk, tumor, abscess), psychogenic
Referred pain: From heart, lungs, esophagus, genitalia (e.g., cardiac ischemia, pneumonia, pneumothorax, pulmonary embolism, esophagitis, esophageal spasm, esophageal rupture)
ACUTE, CATASTROPHIC ABDOMINAL PAIN
Intense abdominal pain of acute onset or pain associated with syncope, hypotension, or toxic appearance necessitates rapid yet orderly evaluation. Consider obstruction, perforation, or rupture of hollow viscus; dissection or rupture of major blood vessels (esp. aortic aneurysm); ulceration; abdominal sepsis; ketoacidosis; and adrenal crisis.
BRIEF HISTORY AND PHYSICAL EXAMINATION
Historic features of importance include age; time of onset of the pain; activity of the pt when the pain began; location and character of the pain; radiation to other sites; presence of nausea, vomiting, or anorexia; temporal changes; changes in bowel habits; and menstrual history. Physical exam should focus on the pt's overall appearance [writhing in pain (ureteral lithiasis) vs. still (peritonitis, perforation)], position (a pt leaning forward may have pancreatitis or gastric perforation into the lesser sac), presence of fever or hypothermia, hyperventilation, cyanosis, bowel sounds, direct or rebound abdominal tenderness, pulsating abdominal mass, abdominal bruits, ascites, rectal blood, rectal or pelvic tenderness, and evidence of coagulopathy. Useful laboratory studies include hematocrit (may be normal with acute hemorrhage or misleadingly high with dehydration), WBC with differential count, arterial blood gases, serum electrolytes, BUN, creatinine, glucose, lipase or amylase, and UA. Females of reproductive age should have a pregnancy test. Radiologic studies should include supine and upright abdominal films (left lateral decubitus view if upright unobtainable) to evaluate bowel caliber and presence of free peritoneal air, cross-table lateral film to assess aortic diameter; CT (when available) to detect evidence of bowel perforation, inflammation, solid organ infarction, retroperitoneal bleeding, abscess, or tumor. Abdominal paracentesis (or peritoneal lavage in cases of trauma) can detect evidence of bleeding or peritonitis. Abdominal ultrasound (when available) reveals evidence of abscess, cholecystitis, biliary or ureteral obstruction, or hematoma and is used to determine aortic diameter.
The initial decision point is based on whether the pt is hemodynamically stable. If not, one must suspect a vascular catastrophe such as a leaking abdominal aortic aneurysm. Such pts receive limited resuscitation and move immediately to surgical exploration. If the pt is hemodynamically stable, the next decision point is whether the abdomen is rigid. Rigid abdomens are most often due to perforation or obstruction. The diagnosis can generally be made by a chest and plain abdominal radiograph.
If the abdomen is not rigid, the causes may be grouped based on whether the pain is poorly localized or well localized. In the presence of poorly localized pain, one should assess whether an aortic aneurysm is possible. If so, a CT scan can make the diagnosis; if not, early appendicitis, early obstruction, mesenteric ischemia, inflammatory bowel disease, pancreatitis, and metabolic problems are all in the differential diagnosis.
Pain localized to the epigastrium may be of cardiac origin or due to esophageal inflammation or perforation, gastritis, peptic ulcer disease, biliary colic or cholecystitis, or pancreatitis. Pain localized to the right upper quadrant includes those same entities plus pyelonephritis or nephrolithiasis, hepatic abscess, subdiaphragmatic abscess, pulmonary embolus, or pneumonia, or it may be of musculoskeletal origin. Additional considerations with left upper quadrant localization are infarcted or ruptured spleen, splenomegaly, and gastric or peptic ulcer. Right lower quadrant pain may be from appendicitis, Meckel's diverticulum, Crohn's disease, diverticulitis, mesenteric adenitis, rectus sheath hematoma, psoas abscess, ovarian abscess or torsion, ectopic pregnancy, salpingitis, familial fever syndromes, uterolithiasis, or herpes zoster. Left lower quadrant pain may be due to diverticulitis, perforated neoplasm, or other entities previously mentioned.
IV fluids, correction of life-threatening acid-base disturbances, and assessment of need for emergent surgery are the first priority; careful follow-up with frequent reexamination (when possible, by the same examiner) is essential. Relieve the pain. The use of narcotic analgesia is controversial. Traditionally, narcotic analgesics were withheld pending establishment of diagnosis and therapeutic plan, since masking of diagnostic signs may delay needed intervention. However, evidence that narcotics actually mask a diagnosis is sparse.
For a more detailed discussion
For a more detailed discussion, see Silen W: Abdominal Pain, Chap. 13, p. 108, in HPIM-18.
Abdominal Pain is a sample topic found in
Harrison's Manual of Medicine for Mobile + Web – 18th edition.
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<urn:uuid:933bbc25-9066-4f75-8f32-47a8f497e76e> | seed | The stress response is the human body's reaction to anything that throws off the balance inside it—injury, infection, fear, exercise, or pain. The body reacts with an alarm phase, then a resistance phase, during which it tries to fix the imbalance, and then, if that fails, an exhaustion phase.
The response starts when a part of the brain called the hypothalamus detects stress. The hypothalamus starts the alarm phase by turning on the sympathetic division of the nervous system. The sympathetic nerves release adrenaline. The "adrenaline rush" makes the heart beat harder and faster, raising blood pressure. A person's skin turns pale as blood vessels to the skin constrict and direct the blood to the muscles. Blood vessels to the intestines and kidneys also constrict. The liver releases stored sugar into the blood, hair stands up, and the body begins to sweat. The body's natural response is to run away or fight back; that's why the sympathetic system is called the "fight or flight" system.
Next, the body must enter the resistance phase and fix whatever is causing this stress. If the body has lost blood from an injury, the kidneys can help minimize the loss. The hypothalamus makes the kidneys take water from the urine and put it back into the blood by releasing a protein called antidiuretic (which means "against urination") hormone (ADH).
The adrenal glands (sitting right on top of the kidneys) can also make the kidneys move fluid from the urine back into the blood. But what makes them do it? It's the kidneys, located just below them. When the kidneys' blood supply is reduced during the alarm phase, they release a protein called renin (which means " kidney substance") into the blood. Renin reacts with other proteins in the blood to form angiotensin (which means "blood vessel constricting"). When angiotensin reaches the adrenal glands, their outer layer, the adrenal cortex, releases the hormone aldosterone. Aldosterone makes the kidneys secrete potassium into the urine and reabsorb sodium and water into the blood. This helps maintain blood volume.
As the stress continues, the body uses up its stored glucose . It will need to use its stored carbohydrates , fat, and proteins for energy and to heal damaged cells. Once again, the hypothalamus and adrenal glands tell the body what to do. The hypothalamus releases growth hormone and the adrenal cortex releases cortisol. Both of these hormones tell the body to release stored compounds from body fat, muscles, and the liver. In this case, the adrenals get their orders to release cortisol from the hypothalamus when it releases a protein called corticotropin (meaning "cortex stimulating") releasing hormone (CRH).
The hypothalamus does not affect the adrenals directly. Instead, the CRH goes to the pituitary gland, just below the brain. The pituitary sends the message on to the adrenals by releasing adrenocorticotropic (meaning "adrenal cortex stimulating") hormone (ACTH). This chain of command, in which the hypothalamus tells the pituitary what to do, and then the pituitary tells the adrenals, is called the hypothalamic-pituitary-adrenal axis. When ACTH reaches the adrenals, the adrenal cortex releases cortisol into the blood. Cortisol makes the body release stored chemicals into the blood.
With ADH and aldosterone helping the body preserve blood volume, and cortisol and growth hormone providing food for the cells, the body should recover. But if this isn't enough help, the body could become exhausted and suffer organ damage.
Long-term or chronic stress can keep the body's stress response too active. That can cause high blood pressure by increasing blood volume. It can make the body lose too much potassium in the urine or develop high blood sugar levels. Also, cortisol suppresses the immune and inflammatory systems (that is why the similar compound cortisone is used to treat rashes). With high cortisol levels, the body has trouble fighting off infections. Stress even makes some animals more prone to cancer. The stress response helps saves the body from life-threatening injury, but it may need to be controlled with medications, biofeedback, or meditation to keep it from causing new illnesses or complications.
Patricia S. Bowne
Martini, Frederic H. Fundamentals of Anatomy and Physiology. Upper Saddle River, NJ: Prentice Hall, 1998.
Porth, Carol M. Pathophysiology: Concepts of Altered Health States. Philadelphia, PA: Lippincott Press, 1998. |
<urn:uuid:8d5f9a39-5558-477f-816b-e31118307375> | seed | ASCO Annual Meeting
June 4, 2012
According to a recent study, women survivors of childhood cancers who received low doses of radiation therapy aimed at the chest had a high risk of developing breast cancer at a young age. An increased risk of breast cancer is a known long-term side effect or late effect of moderate to high-dose radiation therapy to the chest. That is why the current screening recommendations for childhood cancer survivors recommend annual breast cancer screening for women who received moderate to high doses (20 or more Gray or Gy, a measure of the radiation dose) of radiation therapy to the chest. This study shows that even childhood cancer survivors who received lower doses of radiation therapy have a higher risk of breast cancer, and they may need to follow similar breast cancer screening recommendations.
In this study, researchers looked at information from more than 1,200 women who participated in the Childhood Cancer Survivor Study and 4,570 women who were the first-degree relatives (mother, sister, daughter) of participants in the Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study. The WECARE Study was made up of women with breast cancer who lived at least one year after their diagnosis.
Researchers found that 24% of childhood cancer survivors developed breast cancer before age 50. For those treated for Hodgkin lymphoma as children, 30% developed breast cancer before age 50. For women who received radiation therapy to the chest in doses ranging from 10 to 19 Gy, 7% developed breast cancer before age 40, compared with 12% of those who received radiation therapy doses of 20 Gy or higher. As a comparison, this increase in risk is similar to the known risk for women who have a mutation in the BRCA1 and BRCA2 breast cancer genes.
What this means for patients
“While radiation doses have decreased and techniques have improved, radiation therapy is still an essential part of treatment for many childhood cancers,” said lead author Chaya S. Moskowitz, PhD, Associate Member and Associate Attending Biostatistician at Memorial Sloan-Kettering Cancer Center in New York City. “The goal is to cure the cancer for more children while lessening future health problems. Our results suggest that young women treated with lower doses of radiation who are not currently being screened also have a higher risk of breast cancer and might benefit from a similar screening schedule.”
If you are a childhood cancer survivor or if you have a child who received cancer treatment, talk with the doctor about the recommended schedule for follow-up care. The doctor's office can help you create a record of the written history of the diagnosis, the treatment given, and the recommendations for follow-up care. In addition, ASCO offers cancer treatment summary forms to help keep track of the cancer treatment received and develop a survivorship care plan.
Questions to Ask the Doctor
- What type of cancer did I or my child have?
- What treatments were given?
- What are the long-term side effects of these treatments, including the risk of secondary cancers?
- What is the recommended follow-up care schedule?
- What cancer screening tests are recommended?
For More Information |
<urn:uuid:863544d9-f826-4eb3-a22e-7c086319401b> | seed | Acid reflux occurs when stomach contents moves backward into the esophagus. It’s also called acid regurgitation or gastroesophageal reflux (GER). Acid reflux is a common digestive condition. According to the American College of Gastroenterology (ACG), more than 60 million Americans experience acid reflux at least once a month. More than 15 million Americans experience it every day.
Acid reflux usually causes a burning sensation in the chest. The sensation radiates up from the stomach to the mid-chest or throat. This is also known as heartburn.
Acid reflux may also cause a sour taste in the back of the mouth. Chronic reflux can sometimes lead to difficulty swallowing and in some cases it can even cause breathing problems like asthma.
What Causes Acid Reflux?
The muscle at the end of the esophagus is called the lower esophageal sphincter (LES). The LES is a one-way valve that normally opens for limited amounts of time when you swallow. Acid reflux occurs when the LES doesn’t close properly or tightly enough. A faulty or weakened LES allows digestive juices and stomach contents to rise back up into the esophagus.
Large meals that cause the stomach to stretch a lot can temporarily loosen the LES. Other factors associated with reflux include:
- hiatal hernia (when part of the stomach pushes up through the diaphragm)
- consuming particular foods (particularly carbonated beverages, coffee, and chocolate)
If you notice that your reflux only occurs with certain foods, try eliminating them from your diet. Some people also find that sitting up straight during and after eating improves their symptoms.
Types of Acid Reflux
Most people experience occasional acid reflux or GER. However, in some cases the digestive condition is chronic. It’s considered gastroesophageal reflux disease (GERD) if it occurs more than twice a week.
Acid reflux can affect infants and children as well as adults. Children under 12 usually don’t experience heartburn. Instead they have alternative symptoms like:
- trouble swallowing
- dry cough
- laryngitis (loss of voice)
These alternative symptoms can also appear in adults.
Infant Acid Reflux
Adults aren’t the only ones affected by acid reflux. According to the National Digestive Diseases Information Clearinghouse (NDDIC), more than half of all babies experience infant acid reflux during their first three months of life. It’s important for your pediatrician to differentiate between normal reflux and GERD.
Spitting up and even vomiting is normal and may not bother the baby. Other signs of normal reflux include:
- arching the back during or immediately after feedings
- poor feeding
These symptoms generally aren’t harmful to the baby.
GERD in children can easily be missed. Infant acid reflux usually goes away on its own around 12 to 18 months of age. If symptoms persist beyond 18 months of age or become severe, talk to your child’s pediatrician. Your child’s symptoms may be a sign of GERD. Serious symptoms include:
- a lack of weight gain
- refusing to eat
- breathing problems
Call your pediatrician immediately if your infant:
- vomits large amounts
- spits up green or brown fluid
- has trouble breathing after spitting up
To reduce reflux symptoms, your pediatrician may suggest:
- burping the baby a few times during a feeding
- giving more frequent, smaller meals
- keeping the baby upright for 30 minutes after eating
- adding up to 1 tablespoon of rice cereal to 2 ounces of infant milk (if using a bottle)
- changing your diet (if you are breast-feeding)
- changing the type of formula
- certain over-the-counter or prescription medicines to control symptoms
You also may be referred to a pediatric gastroenterologist. Sometimes further testing is necessary.
Esophagitis is a general term for inflammation of the esophagus. It can be accompanied by irritation.
Reflux esophagitis is a type of esophagitis associated with GERD. It’s caused by stomach acid backing up into the esophagus. This damages the esophageal tissues. It often causes heartburn, which may become chronic.
Gastroesophageal Reflux Disease (GERD)
GERD is a chronic digestive disease. It affects people of all ages, including children. It’s the more serious form of GER and can eventually cause more serious health problems if left untreated. Acid reflux that occurs more than twice a week and causes inflammation of the esophagus is considered to be GERD.
Most people with GERD experience symptoms such as:
- trouble swallowing
- a feeling of excessive fullness
Consult your doctor if you have symptoms, or use over-the-counter (OTC) antacids or reflux medications for more than two weeks.
Long-Term Outlook of Acid Reflux
Living with acid reflux is inconvenient. Fortunately, symptoms can generally be controlled through:
- stopping smoking
- reducing alcohol consumption
- eating less fat
- avoiding foods that set off attacks
- losing weight
- sleeping in different positions
- anti-reflux medication
Most people with reflux will not have long-term health problems. However, GERD can increase the risk of Barrett’s esophagus. This is a permanent change in the lining of the esophagus.
Barrett’s esophagus increases the risk of esophageal cancer. However this type cancer is very rare, even in people with Barrett’s esophagus. According to the National Center for Biotechnology Information (NCBI), over a period of 10 years, only 10 out of 1,000 people with Barrett’s will develop cancer. Nevertheless, patients with chronic, unremitting GERD despite medical treatment are often referred for endoscopy. In this procedure, a specialist doctor will examine the lining of your esophagus using a specialized instrument (endoscope), looking for changes of Barrett’s esophagus or cancer in order to try and find the problems early enough to be able to offer you effective treatment. |
<urn:uuid:9567bcbe-47ab-480b-91f6-0581d9080069> | seed | Eating foods exposed to toxaphene is the most probably way of exposure. Foods such as fish and shellfish or game animals such as raccoons taken in areas contaminated by toxaphene may experience somewhat higher intakes of toxaphene because those animals tend to concentrate toxaphene in their fatty tissues. People may also be exposed to toxaphene by eating contaminated soil or by inhaling contaminated air, especially near waste sites.
Infants may be exposed through breast milk and unborn children can be exposed through the mother's blood stream if she is exposed to toxaphene.
Once toxaphene enters the body, it rapidly spreads to all organs. Toxaphene is quickly broken down in the body and excreted in urine and faeces. Approximately 90% of the toxaphene is eliminated from the body within 24 to 36 hours after entering the body. However, studies in animals show that low levels of toxaphene may remain in fat for months.
|NOTE! PREVENT DISPERSION OF DUST! STRICT HYGIENE!||General First Aid: IN ALL CASES CONSULT A DOCTOR!|
|Route of Exposure||Symptoms||First Aid|
|Inhalation||Fresh air rest.|
|Skin||MAY BE ABSORBED! Redness.||Remove contaminated clothes. Rinse and then wash skin with water and soap.|
|Eyes||Redness.||First rinse with plenty of water for several minutes (remove contact lenses if easily possible) then take to a doctor.|
|Ingestion||Convulsions. Dizziness. Nausea. Vomiting.||Give a slurry of activated charcoal in water to drink. Induce vomiting (ONLY IN CONSCIOUS PERSONS!). Rest. Refer for medical attention.|
Notes for ICSC Information
Decomposes near boiling point. Camphechlor is a reaction mixture of chlorinated camphenes containing 6769% chlorine. Use of this organochlorine pesticide should be discouraged except where there is no adequate alternative. Depending on the degree of exposure periodic medical examination is indicated. Carrier solvents used in commercial formulations may change physical and toxicological properties. Do NOT take working clothes home. Alltox ChemPhene M 5055 Clor Chem T590 Crestoxo Estonox FascoTerpene Geniphene Gyphene Hercules 3956 Melipex Penphene Phenacide Phenatox StrobaneT Toxakil Toxyphene Toxon 63 are trade names. |
<urn:uuid:d0c2f531-f1cf-4d39-82d6-fa287668f167> | seed | entrance of digestive system; both mechanical and chemical digestion begin here
throat; passageway for food to the esophagus and air to the larynx
small flap that closes entrance to trachea during digestion
muscular tube that carries bolus from mouth to stomach
muscle between the esophagus and stomach, prevents acidic gastric juices from flowing up into esophagus
located between stomach and small intestine, controls the movement of partially, digested food.
majority of digestion takes place in here, divided into three parts
first part of small intestines, most digestion takes place, chemicals released from liver, gall bladder, and pancreas
second part of small intestines, absorbs nutrients from digested food
last part of small intestines, absorbs enzymes and anything left over by jejunum
Ring of muscles that are between the ileum and the cecum (first part of the large intestine)
receives and eliminates waste products from small intestines, absorbs water from remaining bolus
muscle after the large intestines, temporary storage for feces (stool)
end of digestive tract, opening where feces are expelled
the method used in the esophagus and small intestines to move bolus through
pepsinogen and HCl
two main chemicals released in stomach
organ that produced bile
process in which bile breaks down fat
secretes pancreatic juice into the duodenum, where it mixes with bile to digest food; also produces sodium bicarbonate, a base that neutralizes stomach acid
organ that stores bile
very small blood vessels that absorb nutrients
hepatic portal system
brings blood from digestive system to liver for processing
released in stomach, reacts with HCl to create pepsin
The inactive form of pepsin that is first secreted by specialized (chief) cells located in gastric pits of the stomach.
the process of taking food into the body through the mouth (as by eating)
The breakdown of complex organic molecules into smaller components by physical and chemical means
the taking up of digested molecules into the cells of the digestive tract
the removal of waste food materials from the body
Protein digestion - turns proteins into small polypeptides
Also: an enzyme present in gastric juice that begins the hydrolysis of proteins in the stomach
Enzyme that breaks down fat droplets (emulsified) into: glycerol, fatty acids, and glycerides
Carbohydrate digestion - turns polysaccharides (starch, glycogen) into smaller polysaccharides (maltose)
enzyme from pancreas that breaks down starch
Nucleic acid digestion - turn DNA/RNA into nucleotides
Made in the pancreas, _______ turns small polypeptides (once protein) into smaller polypeptides in the lumen of sm. int.
Made in the pancreas, and activated by trypsin, _______ also turns small polypeptides (once protein) into smaller polypeptides in the lumen of sm. int.
enzyme that breaks down maltose in the small intestin
enzyme that breaks down sucrose into monosaccharides in the lumen of the small intestine
enzyme that breaks down lactose into monosaccharides in the lumen of the small intestine
waste product, mostly cellulose, e. coli, water, and bilirubin
food that is regurgitated for more mechanical digestion (common for cows, rabbits, etc.)
A small lymph vessel located inside of the villi of the small intestine
forms a bolus (ball) out of the chewed food + pushes it to the back of the mouth into the pharynx
protects stomach lining from acid, w/o it would be stomach ulcers
a food substance that provides bulk but is not digested, healthy colon
releases saliva into the mouth
where digestive fluids are added and most of the chemical digestion occurs
why is the duodenum important?
Through emulsification, _______ disperses fat globules into droplets of fat.
absorbs nutrients into the bloodstream; folds in small intestine that make larger area for food absorption into the blood
paste of food made by physical digestion in the stomach
Tube shaped organ at the top of the trachea
another name for salivary amylase
Q-How long does food stay in your stomach for?
Q-Stomach lining is replaced every...
Q-What is the largest internal organ of the body?
what enzyme is found in the large intestines that breaks up cellulose, or plant material?
produce digestive enzymes that break down cellulose; unable to in humans b/c we have a tiny ______
Enzyme that breaks down proteins
Nucleic acid digestion - turn nucleotides into nucleosides
Nucleic acid digestion - turn nucleosides into: nitrogenous bases, sugar, and phosphates
hormone produced in the stomach wall that stimulates sustained secretion of gastric juice
enzymes, mucus and acid secreted from stomach glands
large intestine doesn't absorb water
large intestine absorbs too much water
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<urn:uuid:f8e2d183-24b7-4a00-ab4d-924e52ca2d67> | seed | Cancer, neoplasia, neoplasm and tumor are interchangeable terms that refer to a condition of unrestricted cell growth caused by abnormal and uncontrolled cell division. Cancer may spread from the place of its origin to other parts of the body through the lymphatic system or the blood stream.
Cat liver cancer can be the result of:
- A primary liver tumor of the liver cells.
- Lymphoma in cats or cancer of the lymphoid tissue or blood cells connected with the liver.
- Secondary liver cancer, which has spread from other organs and affected the liver.
Just like dog liver cancer, primary liver cancer in cats is rare, and most of the time, the liver is affected due to a cancerous growth having metastasized (spread) from distant or neighboring organs. Primary liver cancer can also be benign or malignant.
Benign tumors are harmless and do not cause any illness. They pose a threat only if they are large enough in size to put physical pressure on other abdominal organs or bleed after rupturing. Sometimes very large but benign liver tumors may cause blood sugar levels to drop.
Many chemicals and medicines are not toxic in their original state, but are metabolized by the liver into carcinogenic substances. These carcinogens can cause cancerous growths within the liver, leading to primary liver cancer. As these are actually meant to be passed out through urine or feces, they may also cause cancer on their way out. Urethral cancer in dogs and cats is one of the common examples of cancer caused in this manner.
The liver, however, is the favorite destination of cancers that originate in other parts of the body. This fact is hardly surprising, since the liver is one of the biggest organs in the body and is involved in most of the body’s internal activities. Cat cancer that spreads is malignant in nature, and the very fact that it has spread up to the liver means that it has approached its terminal stage, where treatment is extremely difficult.
If your cat has a benign tumor in the liver, it may be surgically excised and has a good prognosis. Even if a bigger part of the liver is affected and has to be removed, the huge regenerative capacity of hepatic cells ensures a good quality of life after surgery. Cats with primary liver cancer have an average survival time of only one year even after surgery. |
<urn:uuid:a51b713f-b90f-483d-96da-2e664501232b> | seed | Evaluating Ovarian Function
One of the most common fertility diagnoses, ovulation disorders are usually easy to treat. The female ovaries provide two key functions: they produce a mature egg to be available for fertilization each month (ovulation) and they deliver the hormones estrogen and progesterone, which are essential to establishing and maintaining pregnancy. A hormone is a ‘chemical messenger,’ that influences a given cell, organ or function in the body. Hormones regulate vital functions such as growth, metabolism, sexual function and reproduction. While up to 20 percent of infertile couples are diagnosed with ovulation disorders; 90 percent of women are able to achieve ovulation, with most all becoming pregnant depending on a woman’s age.
There are a number of ways to tell whether a woman is ovulating regularly and producing sufficient amounts of hormones:
Medical examination. The first step in assessing ovarian health is to receive a complete physical and pelvic examination, as well as a detailed medical history. Such an exam will also note:
- Menstrual history (the patient’s history well as that of relevant family members). If a woman is not having regular periods, or is not menstruating at all, this is a clear indication that there is a problem with ovulation.
- Sexual and contraceptive history
- Any previous pelvic surgery
- Marked weight gain or loss, and assessment of nutritional status as well as diet and any history of anorexia or bulimia
- Recent stressful events
- Exercise level
- Health of the adrenal, thyroid and pituitary glands, responsible for moderating key reproductive hormones
Pelvic ultrasound. Ultrasound exposes part of the body to high frequency sound waves in order to produce an image of that area. The ultrasound is brief, non-invasive and painless. For a pelvic ultrasound, a slender instrument called a transducer is inserted into the vagina. The transducer sends out high frequency sound waves and then listens for returning echoes from tissues in the body. The resulting image, viewed in ‘real time,’ can indicate the health of the ovarian egg follicles as well as any problems such as ovarian cysts.
Serum Progesterone, Thyroid and Prolactin blood tests. These are blood tests to measure hormones essential for establishing and maintaining healthy pregnancies:
- Serum progesterone test. This measures levels of the ovarian hormone progesterone, which plays a vital role in pregnancy. Given approximately one week before the menstrual cycle begins, this blood test can provide one of the simplest and accurate methods of detecting ovulation. Since progesterone levels can fluctuate normally throughout the day, measuring the progesterone value is not as helpful as once thought in determining the hormonal quality of the ovulation.
- Thyroid Stimulating Hormone (TSH) test. Thyroid hormones impact the reproductive system. Both high and low thyroid levels can interfere with hormonal functions essential to ovulation and establishing pregnancy.
- Prolactin test. This hormone is responsible for producing breast milk and is important to pregnancy, however, a high level can inhibit ovulation.
Basal body temperature graph (BBT). This is a way to chart the menstrual cycle in order to see when a patient tends to ovulate. The day after ovulation, and through the end of the monthly menstrual cycle, there is a rise in the progesterone hormone. Progesterone supports the endometrium or uterine lining, creating a nourishing environment for the fertilized egg. With this rise in progesterone comes a rise in body temperature. By tracking these temperature changes, one can estimate their ovulation pattern.
While basal body temperature charting is a simple and inexpensive way to make sure ovulation is occurring, normal variations in temperature can sometimes be misleading and the rigors of taking one’s temperature every morning can be frustrating. In addition to this, the temperature does not rise until AFTER ovulation has occurred so charting cannot be used prospectively to time intercourse. For these reasons, we no longer routinely recommend BBT testing.
Ovulation Predictor Kit (OPK). This provides the only method of actually predicting when ovulation will occur. The test requires a woman to urinate on a stick. The stick then indicates whether there is a rise in the LH or luteinizing hormone responsible for triggering ovulation. For most kits, a positive result means that ovulation will occur within 24 hours. The kit is useful for timing intercourse or insemination. Because it measures the key hormone responsible for ovulation, it can also indicate whether ovulation is or is not actually occurring. We recommend the “Clear Blue Easy” brand of digital test sticks, found in most drug and grocery stores.
Evaluation of egg quality. The other key ovarian function, egg production, can be evaluated through blood tests given at key times in the menstrual cycle. Such tests can indicate the quality of a woman’s eggs, and also the status of the body’s egg supply or ovarian reserve.
It is important for the patient’s physician to know the status of egg production and quality, in order to make treatment decisions that make sense for them. Even when hormone levels indicate that there is diminished egg quality, a woman’s body is often perfectly capable of supporting a pregnancy. In these cases, egg donation (in which a recipient mother uses the eggs of a younger woman) can be very successful.
FSH (follicle stimulating hormone) and Estradiol blood test. Given on day 2 or 3 of the menstrual cycle, this test measures FSH, the primary hormone responsible for prompting egg production, and also estradiol, the most important estrogen hormone, responsible for ovarian health and the growth of the reproductive organs. As women age and egg production decreases, FSH and estradiol levels will increase. This increase signals that the body is having difficulty making eggs and is working harder to ‘make up’ for this shortfall. The ideal FSH level on cycle day 2 or 3 is between 4 and 8 mIU/mL. Lower levels are better than higher levels. Any level greater than 10 mIU/mL suggests a problem with ovarian reserve. The ideal Estradiol level is between 30 and 50 pg/mL and mostly helps to validate that the FSH was drawn at the correct time of the cycle.
Anti-Mullerian Hormone (AMH). A newer test is the Anti-Mullerian Hormone test. This hormone is directly produced by developing follicles in the ovary and is less dependent on where a woman is in her cycle. The ideal level is 1.0 or higher. Higher levels are better.
CCT (Clomid challenge test). This is a more extensive measure of egg supply, in which FSH and Estradiol hormone levels are measured before and after the woman takes the fertility drug Clomid.
Evaluating lack of menstrual cycle. Women who appear to have no menstrual cycle may be given a progesterone-like drug called Provera in order to prompt menstruation. If menstruation after Provera occurs, this indicates that the estrogen hormone is being produced, which in turn indicates a healthy uterus. Lack of menstruation after receiving the Provera may be a sign that the brain’s pituitary gland, responsible for controlling hormone output and balance, is unable to function properly. As long as there is no indication that the woman has entered menopause (such as very high FSH levels), the condition causing lack of ovulation can usually be remedied.
Evaluating fallopian tube function. The delicate fallopian tubes are the pathway to fertility. At ejaculation, sperm are deposited in the vagina and then swim through the cervix and uterus and into the fallopian tube, where they meet and fertilize the egg. Contractions of the fallopian tube smooth muscle and movements of microscopic fimbriae lining the tubes moves the fertilized egg (embryo) back down through the tube to the uterus. Because any blockage or damage to this fragile mechanism can interfere with conception, assessing tubal health is a primary step in evaluation. In many cases, tubal problems can be treated. The following tests are commonly used to determine tubal health:
Hysterosalpingogram. This is an X-ray exam, during which a small amount of dye is injected into the uterus and fallopian tubes. The X-ray is viewed on a screen as the exam is conducted. As the dye disperses, it illuminates any blockages (such as scar tissue or fibroids) that could prevent eggs from traveling to the uterus. The procedure also enables the doctor to view the structure of the uterus itself to see that it is ready to accept a fertilized egg. HSG is performed in the 2nd week of the menstrual cycle (i.e. after menstrual bleeding has stopped but before ovulation). The entire exam takes about 10 minutes. Side effects, if any, include cramping and pelvic pain. Taking Ibuprofen prior to the procedure can help with these symptoms. Most women can resume daily activities right away.
Conditions that may cause infertility
A thorough infertility evaluation can alert a patient’s doctor to conditions in the male or female reproductive system that may be leading to infertility. Click on the below links for a detailed description of some of the more common disorders as well as information about diagnosis and treatment. |