August 15 — Statins reduce the perils facing obese people after they have the bypass surgery that restores blood flow to an endangered heart, a study finds.

The study was done to help settle a running controversy about the ill effects of obesity in such cases, said Dr. Christina C. Wee, an associate professor of medicine at Harvard Medical School, co-director of research in the division of general medicine at Beth Israel Deaconess Hospital and lead author of a report in the Aug. 19 issue of the Journal of the American College of Cardiology.

“We know that obesity, per se, is a risk factor for developing heart disease,” Wee said. “But once you develop it, is obesity more detrimental than not being overweight? There have been different studies with results going both ways.”

To settle the issue, Wee and her colleagues studied the outcome of bypass surgery for 1,314 people in a controlled trial, using their body-mass index as a measure of obesity. They found that a higher BMI was associated with a higher likelihood that arteries would become blocked again.

One arm of the trial compared progression of the condition in people given either low or high doses of a statin.

“What we found was somewhat surprising,” Wee said. “With low-dose statin therapy, obesity was detrimental, with more blockage. What was unexpected was that with high doses of the statin, obesity did not have much of an effect at all.”

While statins are prescribed to lower blood levels of LDL cholesterol, the effect seen in the study probably had a different cause, Wee said.

“We know that statins do more than lower cholesterol,” she said. “They lower inflammation, and people who are obese have greater inflammation. There is a lot of evidence that inflammation in general is not good. Since a person who is obese has more of that going on, statins tend to protect.”

The study offers a good argument for giving statins after bypass surgery, Wee said. “What we can say is that if you have heart disease, particularly if you had bypass surgery, you should be on a good dose of a statin,” she said. The dosage described as “high” in the study now is regarded as standard, Wee added.

“If you are overweight or obese, you really should take your statin and be aggressive about it,” she said. “You get much more benefit than for someone who is thinner.”

Another paper in the same issue of the journal aimed at settling a controversy about the best way to measure the danger of obesity. A prevailing school of thought holds that measuring body-mass index is good enough. Anyone with a BMI of 30 or greater is obese.

Another theory is that not only the amount of fat, but also its distribution matters, with various ways of measuring fat in the waist area indicating more risk of cardiovascular disease and other major problems.

A team at Harvard Medical School tried both methods of obesity measurements used on the 16,332 men in the Physicians Health Study and the 32,700 women in the Women’s Health Study, linking incidence of cardiovascular disease to the obesity described by the two methods.

The waist fat measurements “demonstrated the strongest association with cardiovascular disease and best model fit,” the researchers reported. But they added that “cardiovascular disease risk increased linearly and significantly with higher levels of all indexes.”

SOURCES: Christina C. Wee, M.D., co-director, research, Beth Israel Deaconess Hospital, division of general medicine, Boston; Aug. 19, 2008, Journal of the American College of Cardiology

Disease/Infection News

Scientists in the United States have discovered that elderly survivors of the original 1918 flu pandemic, still have immunity to the virus.

Researchers at Monroe Carell Junior Children’s Hospital at Vanderbilt, have recovered antibodies to the virus, ninety years after it first appeared and caused the deaths of almost 50 million people worldwide.

They also suspect the antibodies could provide effective treatments should another flu pandemic appear imminent.

In a study, led by Dr. James Crowe Junior, a professor of pediatrics and director of the Vanderbilt Program in Vaccine Sciences, researchers collected blood samples from 32 survivors age 91-101 years and found that all reacted to the 1918 virus, suggesting that they still possessed antibodies to the virus.

Samples of the virus used were collected by researchers from Mount Sinai and the Armed Forces Institute of Pathology in 2007 and were taken from the bodies of people killed in the outbreak whose bodies, and the virus, had been preserved in the permanently frozen soil of Alaska.

Professor Crowe’s laboratory was able to make antibodies to the 1918 flu from eight of the samples by isolating the rare B cells which are the immune cells that produce antibodies, and grow them in culture.

Seven produced antibodies to a 1918 virus protein, suggesting that their immune systems were waiting on standby for a long-awaited second outbreak.

The cells showing the highest levels of activity against the virus were then fused with “immortal” cells to create a cell line that secretes monoclonal (or identical) antibodies to the 1918 flu.

These antibodies reacted strongly to the 1918 virus and cross-reacted with proteins from the related 1930 swine flu but not to more modern flu strains.

In order to test if these antibodies still work against 1918 flu in a living animal, Crowe’s collaborators at the Centers for Disease Control and Prevention infected mice with the 1918 flu and then administered the antibodies at varying doses.

It was found that while the mice given the lowest dose of 1918 antibody died, all those given the highest doses of 1918 antibodies survived.

Professor Crowe says although aging typically causes immunity to weaken, these are some of the most potent antibodies ever isolated against a virus and the best antibodies he has ever seen.

The findings suggest that B cells responding to a viral infection and the antibody-based immunity that results, may in fact last a lifetime, even nine or more decades after exposure.

The scientists say these antibodies could be used as potential treatments for future outbreaks of flu strains similar to the 1918 virus and the technology used to develop antibodies against other viruses such as HIV.

Professor Crowe says important lessons being learnt about the 1918 flu can help predict what may happen during a future pandemic.

Researchers at the Scripps Research Institute in La Jolla, California also contributed to the study which was supported by grants from the National Institutes of Health.

Other researchers include Dr. Christopher Basler from the Mount Sinai School of Medicine, and Dr. Eric Altschuler from the University of Medicine and Dentistry of New Jersey Medical School; the study is published online in the journal Nature.

Disease/Infection News

In the first statewide study of extensively drug-resistant tuberculosis (XDR TB) in the United States, California officials have identified 18 cases of the dangerous and difficult-to-treat disease between 1993 and 2007, and 77 cases that were one step away from XDR TB. The study appears in the August 15 issue of Clinical Infectious Diseases, now available online.

California reports almost 3,000 cases of tuberculosis annually, the largest number of TB cases of any U.S. state. California has also led the nation since 2002 in the number of multidrug-resistant tuberculosis (MDR TB) cases-those that are resistant to isoniazid and rifampin, the two antibiotics that form the backbone of TB treatment. XDR TB is resistant to even more classes of antibiotics, including fluoroquinolones and one of three injectable second-line drugs. The authors of the new study evaluated drug susceptibility data of MDR TB cases identified by the California TB Registry between 1993 and 2007, looking for cases that fit the XDR TB definition.

Of the 424 MDR TB cases, 4 percent were XDR and 18 percent were pre-XDR, which are one drug away from XDR TB. The proportion of patients with pre-XDR isolates increased from 7 percent in 1993 to 32 percent in 2007. XDR TB occurred due to inadequate treatment of MDR TB, XDR TB transmission within California, and infection of persons with XDR strains prior to U.S. arrival.

Over the course of the study, TB outcomes improved. Deaths declined among XDR TB cases identified after 2000. However, the authors wrote, strategies must be implemented to identify and cure MDR and pre-XDR TB cases before they develop into XDR TB. Modeling studies suggest that unless evolution of MDR into XDR is slowed, XDR cases could increase exponentially. Prevention is more cost-effective than treatment, they noted.

“Globally, XDR TB has resulted from a combination of poor TB control practices, poor adherence to medications, inappropriate use of second-line drugs, lack of laboratory capacity to culture TB or assess drug susceptibility, and high HIV prevalence,” said lead author Ritu Banerjee, MD, PhD of the University of California at San Francisco. “In order to prevent an escalation in XDR TB we need to ensure adherence to the cornerstones of TB management, which include directly observed therapy, isolation of infectious cases, and contact investigations. We also need to institute routine, rapid, and standardized methods to assess drug susceptibility of TB isolates,” she concluded.

http://www.idsociety.org/

Disease/Infection News

The Seattle Post-Intelligencer border=0>

This article is republished with kind permission from our friends at The Kaiser Family Foundation. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery of in-depth coverage of health policy developments, debates and discussions. The Kaiser Daily Health Policy Report is published for Kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation. Copyright 2008 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Disease/Infection News

Although Yemen — which has recorded 2,431 HIV/AIDS cases — is considered border=0>

This article is republished with kind permission from our friends at The Kaiser Family Foundation. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery of in-depth coverage of health policy developments, debates and discussions. The Kaiser Daily Health Policy Report is published for Kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation. Copyright 2008 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Disease/Infection News

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This article is republished with kind permission from our friends at The Kaiser Family Foundation. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery of in-depth coverage of health policy developments, debates and discussions. The Kaiser Daily Health Policy Report is published for Kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation. Copyright 2008 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Disease/Infection News

Poverty and the movement of people displaced by war have contributed to an increase in the number of HIV/AIDS cases in Sudan, United Nations and Sudanese health officials said border=0>

This article is republished with kind permission from our friends at The Kaiser Family Foundation. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery of in-depth coverage of health policy developments, debates and discussions. The Kaiser Daily Health Policy Report is published for Kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation. Copyright 2008 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Medical Condition News

The largest genetic analysis of its kind to date for bipolar disorder has implicated machinery involved in the balance of sodium and calcium in brain cells. Researchers supported in part by the National Institute of Mental Health, part of the National Institutes of Health, found an association between the disorder and variation in two genes that make components of channels that manage the flow of the elements into and out of cells, including neurons.

“A neuron’s excitability - whether it will fire - hinges on this delicate equilibrium,” explained Pamela Sklar, M.D., Ph.D., of Massachusetts General Hospital (MGH) and the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard, who led the research. “Finding statistically robust associations linked to two proteins that may be involved in regulating such ion channels - and that are also thought to be targets of drugs used to clinically to treat bipolar disorder - is astonishing.”

Although it’s not yet known if or how the suspect genetic variation might affect the balance machinery, the results point to the possibility that bipolar disorder might stem, at least in part, from malfunction of ion channels.

Sklar, Shaun Purcell, Ph.D., also of MGH and the Stanley Center, and Nick Craddock, M.D., Ph.D., of Cardiff University and the Wellcome Trust Case Control Consortiuum in the United Kingdom and a large group of international collaborators report on their findings online Aug. 17, 2008 in Nature Genetics.

“Faced with little agreement among previous studies searching for the genomic hot spots in bipolar disorder, these researchers pooled their data for maximal statistical power and unearthed surprising results,” said NIMH Director Thomas R. Insel, M.D. “Improved understanding of these abnormalities could lead to new hope for the millions of Americans affected by bipolar disorder.”

In the first such genome-wide association study for bipolar disorder, NIMH researchers last fall reported the strongest signal associated with the illness in a gene that makes an enzyme involved the action of the anti-manic medication lithium. However, other chromosomal locations were most strongly associated with the disorder in two subsequent studies.

Since bipolar disorder is thought to involve many different gene variants, each exerting relatively small effects, researchers need large samples to detect relatively weak signals of illness association.

To boost their odds, Sklar and colleagues pooled data from the latter two previously published and one new study of their own. They also added additional samples from the STEP-BD study and Scottish and Irish families, and controls from the NIMH Genetics Repository. After examining about 1.8 million sites of genetic variation in 10,596 people - including 4,387 with bipolar disorder - the researchers found the two genes showing the strongest association among 14 disorder-associated chromosomal regions.

Variation in a gene called Ankyrin 3 (ANK3) showed the strongest association with bipolar disorder. The ANK3 protein is strategically located in the first part of neuronal extensions called axons and is part of the cellular machinery that decides whether a neuron will fire. Co-authors of the paper had shown last year in mouse brain that lithium, the most common medication for preventing bipolar disorder episodes, reduces expression of ANK3.

Variation in a calcium channel gene found in the brain showed the second strongest association with bipolar disorder. This CACNA1C protein similarly regulates the influx and outflow of calcium and is the site of interaction for a hypertension medication that has also been used in the treatment of bipolar disorder.

http://www.nimh.nih.gov/

Medical Condition News

A model for studying the genetics of Angelman syndrome, a neurological disorder that causes mental retardation and other symptoms in one out of 15,000 births, has been developed by biologists at The University of Texas at Austin.

Their research demonstrates that when a particular fruit fly gene, dube3a, is altered, the mutant flies show behavioral dysfunctions similar to those experienced by humans whose UBE3A gene doesn’t function normally.

The work, led by Yaning Wu and Janice Fischer of the Section of Molecular Cell and Developmental Biology, is described in PNAS Early Edition online this week (Aug. 11-15), and will appear in the print version of the Proceedings of the National Academy of Sciences later this month.

“People inherit Angelman syndrome as a mutant UBE3A gene that does not make UBE3A protein,” says Fischer, a professor in the Institute for Cellular and Molecular Biology.

The UBE3A protein is an enzyme that attaches a small protein called ubiquitin to other proteins. Ubiquitin attachment signals that the tagged protein needs to be degraded.

“The simplest explanation for the disease biochemistry is that when UBE3A is not around to do its job, its substrates aren’t being degraded like they should be, and these proteins build up and interfere with brain functions,” Fischer says.

The symptoms of Angelman syndrome in humans include severe mental retardation, epileptic seizures and sleep disturbances.

The work Wu, Fischer and their collaborators have done over the last six years has involved engineering fruit flies with the appropriate mutations in their genes and also particular control transgenes.

The researchers ran the mutant flies through a series of tests, comparing their performances to control groups of flies whose dube3a genes functioned normally. Among other results, the mutant flies weren’t able to climb as well up the sides of plastic containers, weren’t as able to form long-term memories (of aversive shocks) and were more likely to display circadian rhythm irregularities.

In other words, the flies, says Fischer, suffer from a kind of Angelman syndrome, and should therefore offer a useful model for understanding the biochemistry of the disorder in humans. In particular, the fly models may provide clues to which specific protein, or proteins, are accumulating in the brain and causing the dysfunction.

“We’ve known for more than 10 years which gene is at fault, but we haven’t known some of the specifics of the process,” she says. “Now that we know that the fly gene works pretty much the way that the human one does, we can look for the key substrate in flies, and eventually test likely candidates in mice and see if they’re really associated with the disease.”

http://www.utexas.edu/

Medical Condition News

The first ever UK study to seek the opinions of young people with type 1 diabetes, regarding managing their diabetes care at school, uncovered a number of significant misconceptions about the condition.

The study, ‘Young people with type 1 diabetes: the influence of the school environment on self-care’ was carried out by clinical psychologist and D Clin Psych researcher Dr Susannah Lewis, working with the University of Leicester School of Psychology (Clinical Psychology Unit) and the University Hospitals of Leicester NHS Trust.

Its aim was to find out from young people with type 1 diabetes how the management of their condition was influenced by school personnel and peers. Five girls and four boys aged 11-16 years were interviewed for the study. They all had type 1 diabetes, attended state secondary school, and were registered with the children’s diabetes service in a single centre.

The young people reported that teachers and fellow pupils had a significant influence on their diabetes care and their feelings of efficacy regarding the condition. They felt they were more likely to undertake care at school if they were permitted (and encouraged) by teachers to do so.

However, some young people reported that teachers were often unaware that they had diabetes or misunderstood their care needs, making them feel stigmatised by chastising them for undertaking care in class. Sadly it was often left to friends to act as the young person’s advocate and explain their care needs to teachers.

One boy reported: “I took my apple out and started eating while I was working as well, and she (teacher) said, ‘put that in the bin and you get a sanction’. And everybody’s like, but he’s diabetic, oh he’s diabetic, and then she was like, oh sorry.”

There were also reported incidents where teachers did not recognise when pupils were behaving irrationally due to hypoglycaemia (low blood glucose) and disciplined them for their behaviour, whilst friends recognized the symptoms of hypoglycaemia and offered practical assistance.

As one participant commented: “He (the teacher) should have understood a bit more that I was low and didn’t know what I was doing because I was talking complete nonsense, which is a big sign of being low. Well my friends know how to react, but other people in the class will know when I’m low and will tell somebody.”

Incidents of young people’s lives potentially being put at risk by staff not knowing how to treat hypoglycaemia (and calling in parents to administer treatment) were also reported. One mother said that the school telephoned her to come and treat her child “I said by the time I get there she’ll be unconscious”.

The young people also experienced degrees of stigma in relation to having diabetes and the associated care, fearing that they may be perceived as unfavourably “different” by peers and be ridiculed. One participant said: “They’ll think I’m a druggie or something”.

Some chose not to disclose their diagnosis to other pupils or to disclose it only to their close friends. They reported their need to undertake self-care covertly whilst at school (e.g. eating discreetly in class) in order to feel part of the peer group, minimize their feelings of stigma, and allow full participation in lessons and school activities. Others concealed care during lessons, fearing embarrassment if teachers questioned their behaviour in front of other pupils.

Dr Lewis commented: “Previous studies have examined the role of parents in diabetes self-care, and found that parental influence decreases during adolescence. As friendships and school life become more important during adolescence, examining the influence of school personnel and peers was pertinent. There were few studies examining this area, so possible outcomes were unknown”.

“The impact of teachers on young people with diabetes cannot be overestimated, given that poorer self-care increases the risk of complications including unconsciousness, seizures and coma, as well as serious long term problems such as blindness and kidney failure.

“Diabetes is a legally recognised disability. All young people with the condition have the right to appropriate school care to help them fully take part in school life. Young people with diabetes must be allowed to undertake care at any time at school. Schools need to make all staff aware of pupils with diabetes and their related care needs, and staff must be trained in recognising and treating hypoglycaemia.”

“Providing all pupils with diabetes with a school “pass” permitting them to eat/drink discreetly in class and attend the toilet during lessons would help promote care, and allow young people to control the disclosure of their condition and reduce feelings of stigma.

http://www.le.ac.uk/