The Merkel cell polyomavirus (MCPyV) is the only human polyomavirus known to be associated with a rare skin cancer, known as Merkel cell carcinoma, according to a new study published online September 23 in the Journal of the National Cancer Institute.

The majority of patients with Merkel cell carcinoma carry MCPyV, but little is known about the polyomavirus’ prevalence in the general population and the association between circulating antibodies against MCPyV and the rare skin cancer.

Denise A. Galloway, Ph.D. and Paul Nghiem, M.D., Ph.D., of Fred Hutchinson Cancer Research Center in Seattle, and colleagues investigated the levels of antibodies against all five human polyomaviruses in plasma from 41 patients with Merkel cell carcinoma and 76 matched control subjects. Seroprevalence of polyomavirus-specific antibodies for McPyV and the other four polyomaviruses””BK, JC, WU, and KI””was also determined in another 451 control subjects, who represented the general population. MCPyV DNA was determined in tumor tissue specimens.

The authors found that 36 (88%) of 41 patients with Merkel cell carcinoma carried antibodies against MCPyV compared with 40 (53%) of the 76 control subjects. MCPyV DNA was detectable in 24 (77%) of the 31 Merkel cell carcinoma tumors available, with 22 (92%) of these 24 patients also carrying antibodies against MCPyV. Among the 451 control subjects, prevalence of antibodies against the five human polyomaviruses was 92% for BK virus, 45% for JC virus, 98% for WU polyomavirus, 90% for KI polyomavirus, and 59% for MCPyV.

Although infection with MCPyV is common in the general population, MCPyV, but not the other four human polyomaviruses, appears to be associated with Merkel cell carcinoma.

“It should be remembered that Merkel cell cancer is rare”¦,” the authors write. “Thus, although antibody reactivity against MCPyV was associated with an increased risk of developing cell cancer, the absolute risk of cancer development in antibody”“positive individuals is exceeding low.”

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On the Net:

• Journal of the National Cancer Institute

Scientists now have a better understanding of a perplexing gene that is associated with susceptibility for a wide spectrum of severely debilitating mental illnesses. Two independent research studies published by Cell Press in the September 24th issue of the journal Neuron provide fascinating insight into the molecular mechanisms that link disrupted-in-schizophrenia 1 (DISC1) with the proper development and migration of neurons in the hippocampus, a brain area involved in learning and memory and associated with the pathology of schizophrenia.

Previous work established a key role for DISC1 in the process of neurogenesis, which occurs constitutively throughout life in a part of the hippocampus called the dentate gyrus. However, the signaling mechanisms by which DISC1 regulates the complex events of neuronal development have remained elusive. “Despite the initial promise that the study of DISC1 function would reveal susceptibility mechanisms of major disorders, including schizophrenia and bipolar disorder, a comprehensive picture of its function is far from complete, in part because DISC1 seems to have multiple roles in brain cell physiology,” explains Dr. Atsushi Enomoto from Nagoya University Graduate School of Medicine in Japan.

Dr. Enomoto, along with Dr. Masahide Takahashi and other colleagues, found that DISC1 interacts with the actin-binding protein Girdin to regulate the development of nerve cell processes called axons. Girdin was previously identified as a substrate for AKT, another gene linked with schizophrenia, and is thought to be required for normal cellular structure. Cells from the dentate gyrus of neonatal mice lacking Girdin exhibited profound deficits in axon sprouting.

Further, inhibition of DISC1/Girdin interaction resulted in abnormal migration and positioning of developing neurons, leading to a massive disorganization of the dentate gyrus. “Our work identifies Girdin as an intrinsic factor in postnatal development of the dentate gyrus and provides insights into the critical role of the DISC/Girdin interaction in postnatal neurogenesis in the dentate gyrus,” offers Dr. Takahashi.

In a separate study, Dr. Guo-li Ming from the Johns Hopkins University School of Medicine in Maryland found that DISC1 suppression in newly formed neurons in the adult hippocampus led to overactivation of AKT. Further, DISC1 interacted with AKT binding partner KIAA1212. KIAA1212, which is the same molecule as Girdin, enhanced AKT signaling in the absence of DISC1.

Dr. Ming and her colleagues went on to show that defects in neuronal development that were stimulated by either DISC1 suppression or genetically enhanced AKT signaling were rescued by pharmacological inhibition of mammalian target of rapamycin (mTOR), an AKT downstream target. “Our study identifies the AKT-mTOR signaling pathway as a critical DISC1 target in regulating neuronal development and provides a framework for understanding how multiple susceptibility genes may functionally converge onto a common pathway in contributing to the etiology of certain psychiatric disorders,” says Dr. Ming.

Taken together, the research findings shed light on why disruption of DISC1 can lead to inappropriate migration and positioning of adult born neurons, and, ultimately a pathological disorganization of the hippocampus. “Future characterization of a core molecular pathway with a focus on DISC1 and other schizophrenia susceptibility genes may lead to a profound advance in understanding schizophrenia and the development of therapeutic interventions,” adds Dr. Ming.

PDF 1:

The researchers include Ju Young Kim, Xin Duan, Cindy Y. Liu, Mi-Hyeon Jang, Junjie U. Guo, Nattapol Pow-anpongkul, Eunchai Kang, Hongjun Song, and Guo-li Ming, of Johns Hopkins University School of Medicine, Baltimore, MD.

PDF 2:

The researchers include Atsushi Enomoto, Nagoya University Graduate School of Medicine, Nagoya, Japan, Nagoya University, Nagoya, Japan; Naoya Asai, Nagoya University Graduate School of Medicine, Nagoya, Japan, Takashi Namba, National Institute of Neuroscience, Tokyo, Japan, Juntendo University School of Medicine, Tokyo, Japan, Yun Wang, Nagoya University Graduate School of Medicine, Nagoya, Japan, Takuya Kato, Nagoya University Graduate School of Medicine, Nagoya, Japan; Motoki Tanaka, Japan Science and Technology Agency, Nagoya, Japan; Hitoshi Tatsumi, Nagoya University Graduate School of Medicine, Nagoya, Japan; Shinichiro Taya, Nagoya University Graduate School of Medicine, Nagoya, Japan, Core Research for Evolutionary Science and Technology (CREST), Japan Science and Technology Agency, Saitama, Japan; Daisuke Tsuboi, Nagoya University Graduate School of Medicine, Nagoya, Japan, Core Research for Evolutionary Science and Technology (CREST), Japan Science and Technology Agency, Saitama, Japan; Keisuke Kuroda, Nagoya University Graduate School of Medicine, Nagoya, Japan, Core Research for Evolutionary Science and Technology (CREST), Japan Science and Technology Agency, Saitama, Japan; Naoko Kaneko, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Kazunobu Sawamoto, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Rieko Miyamoto, Nagoya University Graduate School of Medicine, Nagoya, Japan; Mayumi Jijiwa, Nagoya University Graduate School of Medicine, Nagoya, Japan; Yoshiki Murakumo, Nagoya University Graduate School of Medicine, Nagoya, Japan; Masahiro Sokabe, Nagoya University Graduate School of Medicine, Nagoya, Japan, Japan Science and Technology Agency, Nagoya, Japan; Tatsunori Seki, Juntendo University School of Medicine, Tokyo, Japan, Tohoku University Graduate School of Medicine, Sendai, Japan; Kozo Kaibuchi, Nagoya University Graduate School of Medicine, Nagoya, Japan, Core Research for Evolutionary Science and Technology (CREST), Japan Science and Technology Agency, Saitama, Japan, and Masahide Takahashi, Nagoya University Graduate School of Medicine, Nagoya, Japan.

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On the Net:

• Neuron

A study published on Tuesday suggesting cardiac patients get vaccinated against flu showed that heart problems may account for a huge share of deaths from influenza, AFP reported.

The study looked at mortality figures for acute myocardial infarction — a sudden heart attack — and cardiovascular disease during outbreaks of flu between 1932 and 2008.

The research, which was published in the journal Lancet Infectious Diseases, did not however include the current pandemic H1N1 virus.

Cardiovascular problems were attributed to between 35 and 50 percent of the increase in deaths recorded during influenza outbreaks.

Infectious disease epidemiologists Charlotte Warren-Gash and Andrew Hayward at University College London found that the flu virus causes inflammation and acts on the molecular pathways that control blood coagulation.

They went on to add that those effects could destabilize fatty deposits that line the arterial wall and cause clots that block coronary arteries.

The paper noted that only a few investigations have been carried out into whether flu vaccination helps protect cardiac patients, but the little evidence available suggests it does.

The authors wrote: “We believe influenza vaccination should be encouraged wherever indicated, especially in those people with existing cardiovascular disease.”

Many countries currently recommend vaccines for “seasonal” flu for individuals with chronic medical conditions that generally include cardiovascular disease but not other cardiac problems such as hypertension.

But figures quoted in the study show that relatively few people at risk take up the vaccine. Only 47.2 percent of people with chronic conditions received the seasonal flu vaccine in Britain and only about one-third of heart patients in the U.S. regularly get vaccinated.

It is still unclear whether the study results apply to otherwise healthy people with no history of heart disease. But they say flu viruses could potentially trigger heart attacks in people who have risk factors like high blood pressure or are overweight but show no apparent heart disease.

Dr. Harlan Krumholz, a spokesman for the American Heart Association and professor of medicine at Yale University, said flu has too often been off the radar screen.

“But flu is as important to think about as cholesterol or blood pressure,” he added.

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On the Net:

• Lancet Infectious Diseases
• University College London

For scientists at the European Molecular Biology Laboratory (EMBL) in Monterotondo, Italy, what seemed like a disappointing result turned out to be an important discovery. Their findings, published online this week in the journal Proceedings of the National Academy of Sciences (PNAS), provide conclusive proof that, when a muscle is injured, white blood cells called macrophages play a crucial role in its regeneration. The scientists also uncovered the genetic switch that controls this process, a finding that opens the door for new therapeutic approaches not only to sports injuries but also to diseases such as Duchenne muscular dystrophy.

Normally, macrophages ““ the white blood cells known for engulfing and eliminating bacteria and other infectious agents ““ are drawn to areas of injury. Once there, they act as garbage men, eliminating the dead cells and releasing pro-inflammatory factors, fending off infection. After clearing up the debris, macrophages stop releasing those pro-inflammatory factors, and start making anti-inflammatory factors that promote repair in the damaged area. This shift from clearing debris to promoting building is known as macrophage polarization, and Claus Nerlov, Nadia Rosenthal and colleagues proved that it is essential for muscles to regenerate properly.

“There seems to be this point of no return”, says Rosenthal: “if macrophages don’t make this switch, then the muscle won’t repair itself ““ you just end up with scar, instead of new tissue”.

Nerlov and his research group at EMBL were studying a protein called C/EBPÃŽ², whose production increases in response to inflammation. They had genetically engineered mice in which this boost in C/EBPÃŽ² production was blocked, to see what effect this had on the development of the different cells involved in the immune system. To their dismay, the answer appeared to be “Ëœalmost none’. The modified mice developed normally, and had normal blood cells ““ except their macrophages didn’t polarize. Although this result fell short of the scientists’ expectations of understanding how blood cells develop, it raised an interesting possibility in the context of Rosenthal’s research into muscle regeneration. If these mice could not repair muscle injuries properly, it would prove that macrophage polarization is indispensable for muscle regeneration. The two groups teamed up to investigate how the ability to respond to muscle injury was affected in mice whose C/EBPÃŽ² production boost had been blocked. Their findings proved that macrophages still migrated to the injured site and cleared the debris, but because they failed to make that all-important switch, the muscle didn’t repair properly, becoming scarred instead.

At a stroke, the EMBL scientists confirmed the importance of macrophages in repairing muscle tissue and discovered its genetic basis. Normally, inflammatory factors trigger an increase in C/EBPÃŽ² production, which in turn activates genes that cause the macrophage to polarize.

“From a medical point of view, it would seem that the trick to improve muscle repair is finding a way to increase C/EBPÃŽ² production and keep it high”, Nerlov concludes, adding “if we can now figure out exactly which key genes C/EBPÃŽ² controls, that will give us even more potential targets.”

As well as investigating the other steps on this molecular pathway, the scientists are currently studying a possible role for macrophage polarization in repairing heart muscle, with a view to better understanding and treating heart disease.
Source Article

Ruffell, D., Mourkioti, F., Gambardella, A., Kirstetter, P., Lopez, R. G., Rosenthal, N. & Nerlov, C. A CREB-C/EBPÃŽ²cascade induces M2 macrophage-specific gene expression and promotes muscle injury repair, PNAS online Early Edition, 21-25 September 2009. 

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Image Caption: This microscopy image, taken ten days after injury, shows that the muscle fibers of normal mice (left) had re-grown, while in mice which couldn’t boost C/EBPÃŽ² production (right) there were still many fibers that had not regenerated (arrowheads), and the tissue had a number of scars (arrows).

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• European Molecular Biology Laboratory
• PNAS

Traumatic spinal cord injury causes permanent disability or loss of movement (paralysis) and sensation below the site of the injury. Currently, there are no treatments that can reverse the damage to the spinal cord, there are only approaches to prevent further damage and to help people return to an active lifestyle. However, Philip Popovich and colleagues, at the Ohio State University College of Medicine, Columbus, have studied the problem in mice and identified potential new therapeutic targets for minimizing injury and/or promoting repair after traumatic spinal cord injury

Traumatic injury to the spinal cord triggers a series of responses by the body that cause further damage to the spinal cord and additional loss of nerve cell function. One of these responses is activation of immune cells known as B cells. In the study, it was found that following traumatic spinal cord injury, mice lacking B cells showed improved recovery of movement when compared with normal mice. They also had a smaller area of damage in the spinal cord. Further analysis indicated that B cells worsened outcome in the mice by producing molecules known as antibodies and therefore the authors suggest that therapeutics that remove B cells or antibodies or that inhibit B cell responses might be of benefit to individuals who experience traumatic spinal cord injury.

In an accompanying commentary, Gregory Dekaban and Sakina Thawer, at the Robarts Research Institute, Canada, concur that such approaches should be considered, although they caution that studies confirming the importance of B cells in causing damage following spinal cord injury in humans need to be performed.

TITLE: B cells produce pathogenic antibodies and impair recovery after spinal cord injury in mice

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On the Net:

• Journal of Clinical Investigation

Scientists reported on Monday that they are in the process of developing a topical anti-impotence cream.

Writing in the Journal of Sexual Medicine, scientists from the Albert Einstein College of Medicine at Yeshiva University found that topical versions of Viagra, Levitra and Cialis could be absorbed through the skin with fewer side effects, and quicker reaction time.

According to BBC Health, erectile dysfunction pills may have been used by tens of millions of men so far, mostly with great success. However, they do carry the risk of certain side effects, such as headaches, blurred vision, or upset stomach.

Also, men who are at risk of heart attack or stroke are advised to stay away from the tablets.

But the development of a topical erectile dysfunction treatment would resolve these issues, scientists said, because they would allow treatments to be focused on one part of the body, rather than dispersed throughout, as in tablet form.

However, development of such creams could be at least 10 years from fruition, scientists said.

The New York research team studied lab rats that were red to have erectile dysfunction. They used nanoparticles to create a way to encapsulate the drug in the cream form.

Researchers studied the effects of nanoparticles containing Cialis, sialorphin, and nitric oxide, among 11 rats with erectile dysfunction.

“Most of the animals, nearly 90 percent, showed a response to treatment with the nanoparticles,” said co-author Joel M. Friedman.

“In addition, when we applied the nanoparticles at therapeutic doses, we found no indication of systemic side effects,” he said.

“The response time to the nanoparticles was very short, just a few minutes, which is basically what people want in an erectile dysfunction medication,” Dr Kelvin Davies, a researcher with the team, told BBC Health.

“In both rats and humans, it can take 30 minutes to one hour for oral erectile dysfunction medications to take effect.”

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On the Net:

• Journal of Sexual Medicine
• Albert Einstein College of Medicine

SMU researchers expand study that shows promise

As the health care reform debate turns to cutting costs and improving treatment outcomes, two professors at Southern Methodist University in Dallas are expanding a study that shows promise for reducing both the expense and suffering associated with chronic asthma.

Thomas Ritz and Alicia Meuret, both in SMU’s Psychology Department, have developed a four-week program to teach asthmatics how to better control their condition by changing the way they breathe.

With the help of a four-year, $1.4 million grant from the National Institutes of Health, they plan to engage 120 Dallas County patients in four weeks of breathing training by the study’s projected end in July 2011. Their co-investigators include David Rosenfield, also of SMU’s Psychology Department, and Mark Millard, M.D., of Baylor University Medical Center in Dallas.

More than 22 million Americans suffer from asthma at an estimated annual economic cost of more than $19 billion, according to the American Lung Association. The number of cases doubled between 1980 and 1995, prompting the U.S. Department of Health and Human Services to classify the disease as an epidemic in 2000.

During an attack, sufferers tend to hyperventilate, breathing fast and deep against constricted airways to fight an overwhelming feeling of oxygen deprivation.

Unfortunately, this makes the problem worse by lowering the body’s carbon dioxide levels, which restricts blood flow to the brain and can further irritate already hypersensitive bronchial passages.

Patients who “overbreathe” on a sustained basis risk chronic CO2 deficiencies that make them even more vulnerable to future attacks. Rescue medications that relieve asthma symptoms do nothing to correct breathing difficulties associated with hyperventilation.

As part of SMU’s “Stress, Anxiety and Chronic Disease Research Program,” Ritz and Meuret use their biofeedback-based Capnometry-Assisted Respiratory Training (CART) to teach asthma patients to normalize and reverse chronic overbreathing. A hand-held device called a capnometer measures the amount of CO2 exhaled. Using this device, patients learn how to breathe more slowly, shallowly and regularly.

CART techniques could have a positive impact on quality of asthma treatment even as they reduce the need for acute care, Ritz says.

“The research shows that this kind of respiratory therapy can limit both the severity and frequency of asthma attacks,” he says. “That means fewer doctor visits and less frequent use of rescue medications, with the associated savings of both time and money.”

And for those who count any year without a trip to the emergency room as a year with a good treatment outcome, that means a higher quality of life, says Meuret, who lives with asthma herself.

“The training gives patients new ways to deal with acute symptoms, and that helps them to feel more in control,” she says.

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On the Net:

• Southern Methodist University

Most people will recall the West Nile virus scare that incited fear throughout North America just 10 years ago; however new mosquito-borne diseases in the U.S. and Europe are posing a farther greater health risk, an expert in the U.S. said on Friday.

The Chikungunya virus first popped up in Africa in 2005, but has now greatly spread, leaving a trail of outbreaks and enumerable deaths in India and the French island of Reunion. Cases have even been reported in Italy and France, where the virus has started to spread locally.

“We’re very worried,” Dr. James Diaz of the Louisiana University Health Sciences Center told a meeting on airlines, airports and disease transmission sponsored by the independent U.S. National Research Council.

“Unlike West Nile virus, where nine out of 10 people are going to be totally asymptomatic, or may have a mild headache or a stiff neck, if you get Chikungunya you’re going to be sick,” he said.

“The disease can be fatal. It’s a serious disease,” Diaz added. “There is no vaccine.”

Those infected by Chikungunya experience symptoms ranging from fever, headache, fatigue, nausea, vomiting, muscle pain, rash and joint pain. Such symptoms can last a few weeks, but some have even reported excruciating joint pain or arthritis lasting months.

The virus was originally found in Tanzania in 1952. Its name means “that which bends up” in the Makonde language used in northern Mozambique and southeastern Tanzania, Reuters reported.

The virus now poses a threat to the rest of the world because it is carried by the Asian tiger mosquito, which is found in Asia, Africa, Europe, the Americas, Australia and New Zealand.

In the U.S., the mosquito species gravitates toward the southern regions east of the Mississippi, but has been spotted as far as western Texas, Minnesota and New Jersey.

Health officials are especially worried about Chikungunya occurring in the islands of the Indian Ocean, Mauritius, Seychelles and Reunion, which have beach resorts popular with European tourists.

“It is hyper-endemic in the islands of the Indian Ocean,” Diaz told the meeting.

“Travel by air will import the infected mosquitoes and humans,” he added. “Chikungunya is coming.”

He also made the statement that double-infections are possible, as the Asian tiger mosquito is known to carry Chikungunya, dengue fever and malaria.
Diaz says that he expects the disease to have spread more in “Ëœmega-cities’ like Mumbai and Mexico City, which have large and impoverished populations, poor health controls and water systems that provide the perfect conditions for mosquitoes to breed.

The West Nile virus is carried by a different mosquito species. It first appeared in New York in 1999, but can now be found in most of North America.

Image Courtesy James Gathany/CDC

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On the Net:

• Louisiana University Health Sciences Center
• National Research Council

New drug delivery system could significantly lessen side effects

An innovative drug-delivery system ““ nanoparticles encapsulating nitric oxide or prescription drugs ““ shows promise for topical treatment of erectile dysfunction (ED), according to a new study by scientists at Albert Einstein College of Medicine of Yeshiva University.

The new system, tested successfully on a small number of animals, could potentially prevent side effects associated with oral ED medications, if study results can be replicated in humans. That could mean safer and more effective ED therapy for millions of men with heart disease and other health problems affecting erectile function. The study is published today in the online edition of the Journal of Sexual Medicine.

Tens of millions of men worldwide have benefited from oral ED medications such as sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). However, these medications – which belong to a class of drugs called phosphodiesterase type 5 (PDE5) inhibitors – have limitations. They can cause systemic side effects that can be serious. These side effects include headache, facial flushing, nasal congestion, upset stomach, abnormal vision as well as isolated reports of hearing and vision loss. Men who’ve recently suffered a heart attack or stroke or have severe heart disease should use these drugs with caution or not at all. In addition, “an estimated 30 to 50 percent of men with ED do not respond to oral use of PDE5 inhibitors,” says senior author Kelvin P. Davies, Ph.D., associate professor of urology at Einstein.

The drug-delivery system, developed by Einstein scientists, consists of nanoparticles ““ each smaller than a grain of pollen ““ that can carry tiny payloads of various drugs or other medically useful substances and release them in a controlled and sustained manner.

The limited number of topical formulations of ED drugs has so far proven ineffective. This study was done to evaluate whether the Einstein nanoparticles, which have been shown to penetrate the skin, might allow the targeted delivery of compounds that treat ED and thereby avoid the drugs’ systemic effects.

An effective topical therapy could be especially significant for those ED patients ““ particularly men with diabetes ““ who have reduced levels of nitric oxide (NO), the signaling molecule that dilates blood vessels responsible for erectile activity. These men, who often aren’t helped by oral PDE5 inhibitor drugs, may benefit from direct application of NO or the PDE5 inhibitors.

The nanoparticles were tested on a total of 18 rats bred to have age-related ED. The rats were divided into three treatment groups. One group of seven rats received nanoparticles encapsulating NO. A second group of five rats received nanoparticles encapsulating NO plus an experimental ED drug called sialorphin (which has a mechanism of action different from PDE5 inhibitors). A third group of six received nanoparticles encapsulating NO plus tadalafil (Cialis).

Five of the seven rats treated with the NO-containing nanoparticles, and all 11 rats treated with nanoparticles encapsulating NO plus sialorphin or tadalafil showed significantly improved erectile function. None of the seven rats in a control group, which received empty nanoparticles, showed any improvement.

“Most of the animals, nearly 90 percent, showed a response to treatment with the nanoparticles,” says co-author Joel M. Friedman, M.D., Ph.D., professor of physiology & biophysics and of medicine. Dr. Friedman developed the nanoparticles with his son Adam Friedman, M.D., chief resident in the division of dermatology of the department of medicine at Montefiore Medical Center, The University Hospital and Academic Medical Center for Einstein.

“The response time to the nanoparticles was very short, just a few minutes, which is basically what people want in an ED medication,” adds Dr. Davies. “In both rats and humans, it can take 30 minutes to one hour for oral ED medications to take effect.”

Postmortem examination of the tissues at the site of administration showed no signs of local inflammation or toxicity. “In addition, when we applied the nanoparticles at therapeutic doses, we found no indication of systemic side effects,” says Dr. Friedman.

The Einstein research team will carry out safety and dosing studies in rats in the coming months. Clinical studies on humans could begin in a few years if animal studies continue to show that the nanoparticle delivery system is safe and effective. But the investigators caution that the time from a proof-of-concept trial in animals to approved use in humans may be a decade or more.

The paper, “Nanoparticles as a novel delivery vehicle for therapeutics targeting erectile dysfunction,” is published in the September 18, 2009 online edition of the Journal of Sexual Medicine. The lead authors are George Han, an M.D.-Ph.D. student at Einstein, Moses Tar, M.D., assistant professor of urology at Einstein, Dwaraka Srinivasa Rao Kuppam, a technician in the Einstein urology department, Adam Friedman, M.D., of Montefiore Medical Center, and Arnold Melman, M.D., chairman of urology at Einstein, also contributed to the research.

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On the Net:

• Albert Einstein College of Medicine
• Journal of Sexual Medicine

U.S. health officials said Friday 3.4 million doses of H1N1 flu vaccine are expected to be available the first week of October.

Jay Butler, a medical epidemiologist and chief of the Centers for Disease Control and Prevention’s H1N1 vaccine task force, said most of these initial doses of H1N1 vaccine will be the nasal spray form, which is not recommended for pregnant women, people age 50 and older, or those with asthma, heart disease or other chronic diseases. The first doses will primarily be given to healthcare workers.

We would anticipate that once we’re up and going we should be seeing at least 20 million new doses of vaccine weekly going right on into December after when we would hope to reach the capacity of having delivered 195 million doses, Butler said at a news conference.

Right now there’s every indication that we have a good match between the virus that’s causing disease and the vaccines we have to be able to prevent it.

Availability of the vaccine may vary, Butler said.

The H1N1 flu is in all 50 states, but is more prevalent in some areas such as the Southeast and is mainly hitting children and young adults, Butler said.

Most of the illness, appears to be moderate or moderately severe, Butler said.

More conservative treatment, or watchful waiting of localized prostate cancer may be why outcomes have improved, U.S researchers said.

Grace L. Lu-Yao of the Cancer Institute of New Jersey and the University of Medicine and Dentistry of New Jersey’s Robert Wood Johnson Medical School in Piscataway, N.J., and colleagues said the study was based on data from a population-based study that included 14,516 men who were not treated with surgery or radiation for six months after their Stage 1, or Stage 2 prostate cancer diagnosis. They were tracked for about eight years.

The study, published in the Journal of the American Medical Association, found overall and prostate cancer-specific survival rates are higher for men over the age of 65 diagnosed from 1992-2002 with localized prostate cancer — compared with men diagnosed in the 1970s and 1980s.

The researchers attribute 60 percent to 74 percent lower prostate cancer death rates in older men to a number of factors.

Aggressive treatment for prostate-cancer patients age 65 and older does not seem to significantly improve survival, the study said.

The substantial improvement in survival that we observed in our study compared with previous reports might be explained, in part, by additional lead time, overdiagnosis related to prostate-specific antigen testing, or grade migration, among other factors, the study authors said in a statement. Prostate-specific antigen testing identifies disease 6-13 years before it presents clinically.

A British researcher won a prize for work that may help reverse the muscle loss that leaves many senior citizens with too-thin limbs.

The Blue Riband Award was presented in Dublin, Ireland, by The Physiological Society to Beth Phillips for confirming leg blood flow in the elderly slowed after eating, but weight-training helped reduce this effect.

She found that three sessions a week over 20 weeks ‘rejuvenated’ the leg blood flow responses of the older people. They became identical to those in the young, Michael Rennie, who worked with Dr. Emilie Wilkes, Phillips and colleagues at the University of Nottingham in England, said in a statement.

The researchers traced muscle breakdown to the double whammy of not building enough muscle using food protein and of not shutting down insulin production after meals. They linked both to nutrient and hormone delivery failures due to poorer blood supply.

Our team is making good headway in finding more and more out about what causes the loss of muscle with age, Rennie said in a statement. It looks like we have good clues about how to lessen it with weight training and possibly other ways to increase blood flow.

The findings are published in The American Journal of Clinical Nutrition.

Sodium channel gene linked to Dravet syndrome

University of Utah medical researchers have identified a gene with mutations that cause febrile seizures and contribute to a severe form of epilepsy known as Dravet syndrome in some of the most vulnerable patients ““ infants 6 months and younger.

The discovery, published online in PLoS Genetics, means some infants with Dravet syndrome, a type of epilepsy that often begins with fever-induced (febrile) seizures, would benefit from genetic testing to identify whether they have a mutation in the SCN9A gene, which the researchers found causes seizures by affecting sodium channels in the brain. Infants who have the mutation might well be better off not receiving sodium channel blockers, some of the most common anticonvulsant drugs, because they could make a sodium channel-induced seizure worse, the researchers report.

The study was a collaboration of researchers from several departments in the U of U School of Medicine and College of Pharmacy, as well as national and international colleagues. First author Nanda A. Singh, Ph.D., a researcher in the University’s Eccles Institute of Human Genetics, said the SCN9A mutation is the fifth gene discovered to cause febrile seizures and, before now, was not suspected in seizures or epilepsy.

“This new gene gives us a much needed novel target for developing more effective drugs to treat those children with debilitating seizures,” Singh said.

Groundwork for the study was laid by two U of U School of Medicine physicians, Joel Thompson, M.D., and Francis M. Filloux, M.D., professor of pediatrics and neurology, who in the 1990s met a patient whose family had a history of the febrile seizures. After studying the DNA of 46 members of the extended family, researchers at the U of U identified an area on chromosome 2 as a likely place to find the gene mutation associated with the family’s seizures. Using that data, they pinpointed the SCN9A mutation as the seizure-causing gene in the family.

To confirm SCN9A’s role, the researchers used technology pioneered by the University of Utah’s 2007 Nobel laureate in medicine, Mario R. Capecchi, Ph.D., to create mouse models with the gene mutation. The researchers tested the animals for seizures and found the mice with the SCN9A mutation had significantly lower thresholds for developing seizures than mice without the mutation.

“The mouse data confirmed that the SCN9A mutation is causing the febrile seizure disease in this family,” Singh said. The researchers further showed the SCN9A seizure-causing role in approximately 5 percent of 92 unrelated febrile syndrome patients.

The SCN9A gene provides instructions for the body to make sodium channels, which act as conduits and gates to let sodium ions into cells and help conduct electricity for neurons to communicate. But when the gene mutates, it can cause seizures by altering sodium channel function in the brain and preventing neurons from firing properly. Mutations in four other genes had been shown in other studies to cause febrile seizures, and one sodium channel gene in particular, SCN1A, has been found in about half of patients with Dravet syndrome. In DNA collected by Belgium researchers, headed by Peter De Jonghe, Singh and her colleagues found additional SCN9A mutations in about 9 percent of Dravet syndrome patients, while 6 percent had both SCN9A and SCN1A gene mutations.

For infants and children who suffer febrile seizures or have Dravet syndrome, the study offers hope where there often is little to be found, according to Kris Hansen, president of the Epilepsy Association of Utah and mother to a child with Dravet syndrome. “Dravet is such a hard syndrome to control, and any research that gives us reasons for what is happening with our children and hope for the future is absolutely amazing,” Hansen said. “This medical breakthrough will bring prospects of relief to families dealing with the ongoing challenges of Dravet syndrome and febrile seizures.”

Febrile seizures are the most common form of early childhood seizures and strike up to 1 in 20 children in North America. Most infants outgrow them, but in some cases the seizures continue into adulthood. Epilepsy is a disorder of many types of seizures that affects nearly 3 million people in the United States, with approximately 200,000 new cases reported each year. Patients with Dravet syndrome can have febrile and other seizures severe enough to stunt mental and social development.

Because half of Dravet syndrome patients have SCN1A mutations, these patients are tested for that form of the disorder for the mutation. In those who don’t have the SCN1A mutation, Singh suggests a second test could determine if they have the SCN9A mutation. In patients who have one or both of the genes, treatment could be modified to exclude sodium channel-blocking drugs.

The study was funded by the National Institutes of Health, Keck Foundation, and the Salt Lake City-based Ben B. and Iris M. Margolis Foundation.

This study was a collaboration of researchers from the University of Utah School of Medicine’s Department of Human Genetics, divisions of Pediatric Neurology and Medical Genetics, and the College of Pharmacy’s Anticonvulsant Drug Development Program. Researchers from the University of Washington and University of Antwerp, Belgium, also collaborated on the study. Mark F. Leppert, Ph.D., professor of human genetics in the University of Utah School of Medicine was the study’s senior author.

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On the Net:

• University of Utah Health Sciences
• PLoS Genetics

Research: Radial extracorporeal shockwave treatment compared with supervised exercises in patients with subacromial pain syndrome: Single blind randomized study

Supervised exercises are more effective than shockwave treatment to relieve chronic shoulder pain, finds a study published on bmj.com yesterday.

Shoulder pain is the fourth most common type of musculoskeletal pain reported to general practitioners and physiotherapists. Treatments often include physiotherapy, non-steroidal anti-inflammatory drugs, and steroid injections. Physiotherapy can include shockwave treatment, ultrasound, exercises and acupuncture.

Several studies have suggested that shockwave treatment may not be effective, but it continues to be used widely.

So a team of researchers based in Oslo, Norway compared the effectiveness of radial extracorporeal shockwave treatment (low to medium energy impulses delivered into the tissue) with supervised exercises in patients with shoulder pain.

The study involved 104 men and women aged between 18 and 70 years attending the outpatient clinic at Ullevaal University Hospital in Oslo with shoulder pain lasting at least three months.

Participants were randomized to receive either radial extracorporeal shockwave treatment (one session weekly for four to six weeks) or supervised exercises (two 45 minute sessions weekly for up to 12 weeks).

Both groups were similar at the start of the study with regard to age, education, dominant arm affected and pain duration.

All patients were monitored at six, 12 and 18 weeks and were advised not to have any additional treatment except analgesics (including anti-inflammatory drugs) during the follow-up period. Pain and disability were measured using a recognized scoring index.

After 18 weeks, 32 (64%) of patients in the exercise group achieved a reduction in shoulder pain and disability scores compared with 18 (36%) in the shockwave treatment group.

More patients in the exercise group returned to work, while more patients in the shockwave treatment group had additional treatment after 12 weeks, suggesting that they were less satisfied.

These results are in agreement with results from previous trials recommending exercise therapy and do not strengthen the evidence for extracorporeal shockwave treatment, say the authors.

They conclude: “Supervised exercises were more effective than radial extracorporeal shockwave treatment for short term improvement in patients with subacromial shoulder pain.”

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On the Net:

• BMJ

Vegetation in an area may determine its usable water supply, ecologists find

Ecologists have discovered that timber plantations in Hawaii use more than twice the amount of water to grow as native forests use. Especially for island ecosystems, these findings suggest that land management decisions can place ecosystems ““ and the people who depend on them ““ at high risk for water shortages.

“Scientists used to think that forests in same environments use water in the same way,” says Lawren Sack of The University of California at Los Angeles, who coauthored the study with graduate student Aurora Kagawa in the September issue of the ESA journal Ecological Applications. “Our work shows that this is not the case. We need to know the water budget of our landscape, from gardens to forests to parks, because water is expensive.”

Although forests like these Hawaiian timber plantations can be valuable for their contributions to human society, such as fiber, fuel and carbon sequestration, they are dominated by non-native vegetation.

Kagawa, Sack and their colleagues compared the water use of trees in native forests, composed mostly of native ohia trees, with water use in timber plantations containing exotic eucalyptus and tropical ash. The team inserted heated and unheated probes into the trees’ trunks and monitored the temperature differences between the two as sap flowed past them. This technique allowed them to determine the rate of sap flow through the tree. A faster flow rate means that the tree is using more water.

“The way plants grow determines how fast they can take up water,” says Sack. “Plants open their leaf pores, called stomata, to take in carbon dioxide. But when these pores are open, the plants also lose water. Like a wet towel on a clothesline, the insides of the leaf can dry pretty quickly.” Since fast-growing exotic plants typically have more open leaf pores than native, slow-growing trees, Sack says, they lose more water in less time.

The researchers found that individual eucalyptus and tropical ash used three and nine times more water, respectively, than individual ohia trees. Since each of these forests is dominated by these three species, the team was able to scale up their results to predict how much water a whole section of forest uses. Even when including other native plants that use water quickly, such as tree ferns, the tropical ash forests still used water at a rate of 1,800 kilograms of water per square meter per day, more than 2.5 times that of the other forests. The researchers found, however, that the non-native eucalyptus plantation used similar amounts of water as native forest. This is because water use depends on the specific tree species, stand organization and age, and location and climate, says Sack.

Hawaii’s non-native tree plantations were originally intended for timber production and to conserve the islands’ top soil. In the early part of the 20th century, ranches and plantations producing sugar cane and pineapple covered much of Hawaii’s agricultural areas. But years of these practices led to increased soil erosion, and fast-growing non-native trees were planted to hold the soil in place and to preserve water by preventing runoff. At the time, however, the importance of biodiversity and the dangers of exotic species weren’t as clear as they are today.

Especially with climate change rapidly changing many ecosystems, Sack says, it’s vital that land management plans recognize and integrate the fact that water use by plants can affect the clean water supply.

“When making decisions to restore a native forest or preserve or establish a plantation, we need to do a more detailed valuation that includes the cost of water they’re using,” he says. “There are a lot of reforestation projects underway to take up carbon dioxide from the atmosphere, where people are prioritizing fast-growing trees. But we shouldn’t let alien plants sweep over native forests. Our findings make a clear case that we need to know how much water landscapes are using and conserving.”

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Image 1: This Hawaiian forest is made up mostly of native ohia trees, which grow more slowly and use up to 2.5 times less water than exotic timber plantations. Credit: Aurora Kagawa

Image 2: Exotic timber plantations, such as the one pictured, are dominated by exotic species and can use up to 2.5 times more water than native forests. Credit: Aurora Kagawa

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On the Net:

• Ecological Society of America
• Ecological Applications

In a first step toward engineering a drug-free Cannabis plant for hemp fiber and oil, University of Minnesota researchers have identified genes producing tetrahydrocannabinol (THC), the psychoactive substance in marijuana. Studying the genes could also lead to new and better drugs for pain, nausea and other conditions.

The finding is published in the September issue of the Journal of Experimental Botany. Lead author is David Marks, a professor of plant biology in the College of Biological Sciences.

The study revealed that the genes are active in tiny hairs covering the flowers of Cannabis plants. In marijuana, the hairs accumulate high amounts of THC, whereas in hemp the hairs have little. Hemp and marijuana are difficult to distinguish apart from differences in THC.

With the genes identified, finding a way to silence them””and thus produce a drug-free plant “” comes a step closer to reality. Another desirable step is to make drug-free plants visually recognizable. Since the hairs can be seen with a magnifying glass, this could be accomplished by engineering a hairless Cannabis plant.

The researchers are currently using the methods of the latest study to identify genes that lead to hair growth in hopes of silencing them.

“We are beginning to understand which genes control hair growth in other plants, and the resources created in our study will allow us to look for similar genes in Cannabis sativa,” said Marks.

“Cannabis genetics can contribute to better agriculture, medicine, and drug enforcement,” said George Weiblen, an associate professor of plant biology and a co-author of the study.

As with Dobermans and Dachshunds, marijuana and hemp are different breeds of the same species (Cannabis sativa), but marijuana contains much more THC than hemp, which is a source of industrial fiber and nutritious oil.

Hemp was raised for its fiber “” which is similar to cotton but more durable “” in the United States until legislation outlawed all Cannabis plants because they contain THC. Today, marijuana contains as much as 25 percent THC, whereas hemp plants contain less than 0.3 percent.

Hemp was once a popular crop in the upper Midwest because it tolerates a cool climate and marginal soils that won’t support other crops but, after drug legislation, hemp fiber was replaced by plastic and other alternatives. Recent popular demand for hemp products has led some states to consider the economic and environmental benefits of hemp. North Dakota legislation aims to reintroduce it as a crop, and Minnesota is considering similar legislation. At the same time, California and other states permit the medicinal use of marijuana.

“I can’t think of a plant so regarded as a menace by some and a miracle by others,” says Weiblen, who is one of the few researchers in the United States permitted to study Cannabis genetics. In 2006, Weiblen and colleagues developed a DNA “fingerprinting” technique capable of distinguishing among Cannabis plants in criminal investigations.

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On the Net:

• University of Minnesota
• Journal of Experimental Botany

A Memphis hospital attempting to speed vaccine production has met with frustration due to H1N1’s foreign origins and unusual gene mix, doctors said.

The St. Jude research team is trying to speed up the process by injecting chicken eggs with H1N1 and other viruses in an attempt to create hybrids or mutations that might make the virus grow faster, the Memphis Commercial Appeal reported Sunday.

H1N1 is the result of a re-assortment of genes from swine, birds and humans, with pigs serving as the mixing vessel for the flu virus, scientists said.

We’ve never seen this particular blend of virus genes before, Dr. Richard Webby of the department of infectious diseases at St. Jude Children’s Research Hospital said.

Some of H1N1’s gene-carrying RNA came into North America recently from Eurasian pigs, which is a reversal of viruses’ ordinary following of swine export routes from the United States to other countries, the news service said.

That was a big surprise, said Dr. Michael Shaw, associate director of laboratory science in Atlanta’s Centers for Disease Control and Prevention’s influenza department.

Because the H1N1 virus grows half as quickly as many other flu viruses, the federal government expects only approximately 15 million doses to be available as a first batch to be released next month. There is a projected production ultimately of around 200 million doses, the news service reported.

Four of the 12 children ailing as a result of an E. coli outbreak in the English county of Surrey are seriously ill, health officials say.

The Health Protection Agency said since children likely came into contact with the bacteria during a recent visit to the Godstone Farm, which has since been closed to the public, The Sunday Telegraph reported.

To date the outbreak, which is thought to have begun on Aug. 8, has resulted in a total of 36 E. coli cases.

Dr. Angela Iversen, Surrey and Sussex Health Protection Unit director, said officials at the Surrey farm were working with authorities to limit the outbreak.

This is a large outbreak of this infection, Iversen told the Telegraph.

The farm owners are co-operating fully and we are working closely with them and with colleagues across health and local authorities to investigate the source, she added.

Iversen said since E. coli can be spread by handling animals, those who come in contact with animals should thoroughly wash their hands to limit the possibility of being exposed to the bacteria.

Concerned about the H1N1 virus, or swine flu, the French government is urging young and old to forego la bise, the light cheek-to-cheek kiss, officials said.

La bise is a social greeting instilled in French children from a very young age, CNN reported Sunday.

Students are being told to forego la bise and instead write a sign of their their affection on heart-shaped greetings to be slipped into bise boxes, CNN reported.

The French are becoming more accustomed to masks and at least one company wants employees to stop wearing neckties because they are so infrequently washed, CNN reported.

France has confirmed three H1N1 deaths this year from more than 2,800 deaths reported worldwide.

While H1N1 is a concern, the French are traditionally rebellious souls who don’t like being told what to do, said Camille Hercot, a professor at the American University of Paris.

“So if it is really important, and if there are rules in the offices, or

if they get very scared they will, Hercot said, but otherwise they will say ‘pfff.'”

Fears about surgical risk, lack of awareness affect surgery referrals

Overblown fears about surgical risk and lack of awareness about the risk of not operating are among the reasons only half of eligible patients were referred for mitral valve repair, according to a study by doctors at the University of Michigan Cardiovascular Center.

A leaking mitral valve, known as mitral regurgitation or mitral insuffiency, can lead to fatigue, abnormal heart rhythms with irregular heart beats, and congestive heart failure. The longer the leak continues, the more likely there will be permanent heart damage.

Among those who were not operated on, three-fourths of patients met at least one indication for surgery, according to guidelines from the American College of Cardiology and the American Heart Association.

“In general, cardiologists tend to overestimate the risks of surgery and underestimate the potential benefits for patients,” says lead author David S. Bach, professor of internal medicine at the U-M Medical School and cardiologist at the U-M Cardiovascular Center.

Researchers identified 300 patients with moderate to severe mitral regurgitation for the study in the Journal of the American College of Cardiology. Patients had been screened in the University of Michigan Echocardiography Laboratory.

Among them, 188 patients had functional mitral regurgitation, of whom just 30 underwent surgery. Of the 112 patients with severe organic mitral valve regurgitation, only half had surgery.

Surgical risk scores were no different among patients who underwent surgery compared to those who did not.

Existing data show deaths among patients undergoing mitral valve surgery have decreased dramatically in recent years, making the procedure a feasible option.

“I think there remains something of a bias in medicine and cardiology that surgery is risky, and surgery is a failure of our ability to manage the patient medically,” Bach says in an interview. “Mitral valve diseases are not as benign as they were once thought to be, and surgery is not as morbid as it was thought of in the past.”

A review of patient charts showed the most common reasons for not referring patients for surgery were stable heart functioning, an absence of symptoms or presence of other major health problems.

Bach sees mitral valve conditions ““ even relatively common ones like mitral regurgitation ““ as prime examples of conditions that might best be treated in specialized centers with the volume and familiarity to use appropriate interventions and minimize inappropriate ones.

Meanwhile, Bach suggests cardiologists become more familiar with guideline recommendations and the data on which they are based, discuss options more fully with patients, and when possible, involve a surgeon in consultation.

Additional authors: Mazen Awais, M.D., Hitinder S. Gurm, M.D., and Sarah Kohnstamm, M.D., all of the University of Michigan.

Funding: Edwards Lifesciences

Reference: J. American College of Cardiology, Vol. 54, Issue 9, Aug. 25, 2009

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On the Net:

• University of Michigan Health System
• U-M Cardiovascular Center
• American College of Cardiology

Results further support the benefits of TYSABRI for multiple sclerosis patients

Biogen Idec (NASDAQ: BIIB) and Elan Corporation, plc (NYSE: ELN) today announced six-month results of an ongoing, one-year longitudinal, observational, patient-reported outcomes study showing multiple sclerosis (MS) patients taking TYSABRI® (natalizumab) experienced an improvement in both their physical function and psychological well-being. Findings from the study, which was performed in conjunction with HealthCore Inc., a health-outcomes research company, are the first attempt to assess patient experiences with TYSABRI in usual-care settings. The data, presented at the 25th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), shows patients report TYSABRI has an impact in improving their overall quality of life.

“The symptoms that an MS patient deals with on a daily basis result in significant psychological and physical effects that can adversely impact their quality of life,” said William Stuart, M.D., medical director of the Multiple Sclerosis Center of Atlanta. “In a previous pivotal trial, TYSABRI not only showed a reduction in relapse rates and disability progression, but also improved quality of life. Results from this observational study further demonstrate the impact of TYSABRI on improving MS patients’ well-being as reported by patients who live with this disease every day.”

About the study

The study is assessing health outcomes from patients’ perspectives before starting TYSABRI and after the third, sixth and 12th infusions of TYSABRI. A majority of the patients in the study are female (76.3%) with mean age of 46.6 years and mean disease duration of 10 years.

After six TYSABRI infusions, patients reported statistically significant improvement in:

* Disease-specific quality of life (QoL), as measured by the Multiple Sclerosis Impact Scale-29 (MSIS-29), which measures the physical impact of MS in terms of mobility and self care, as well as the psychological impact of MS in terms of anxiety/depression, with lower scores indicating better QoL; and

* General health-related QoL, as measured by the 12-item Short Form Scale (SF-12) health survey, which assesses the physical and mental health, with higher scores indicating better QoL.

Both scales assess patient experience of the physical and psychological aspects of QoL. For the MSIS-29 subscales, there were statistically significant improvements over time for both the physical (baseline 46.87; third infusion 39.60; sixth infusion 39.27 (p< 0.001)) and psychological (baseline 41.56; third infusion 33.77; sixth infusion 33.20 (p< 0.001)) impact scores.

SF-12 physical component summary (baseline 34.20; third infusion 36.05; sixth infusion 36.34 (p< 0.001)) and the SF-12 mental component summary score (baseline 43.25, third infusion 47.35, sixth infusion 47.92 (p< 0.001)) showed statistically significant improvements over time.

What do multiple sclerosis patients experience? Effect of natalizumab on disease-specific quality of life over time (poster P872).

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On the Net:

• Biogen Idec

When a terrorist bomb explodes, a tornado rips through a town, a hurricane devastates a region, or wildfires ravage homes and businesses, plastic surgeons are not typically atop the list of emergency responders.

But they should be, UT Southwestern Medical Center plastic surgeons and disaster experts recommend in the September issue of Plastic and Reconstructive Surgery.

Including plastic surgeons in disaster-relief efforts could improve long-term outcomes for victims of catastrophes, particularly in medical cases that might involve physical scarring and nerve damage, but which can be made worse by lack of quick attention.

“Plastic surgeons are often being overlooked in disaster-planning efforts, particularly in developing medical-team responders,” said Dr. Rod Rohrich, chairman of plastic surgery at UT Southwestern and the study’s senior author. “Plastic surgeons, particularly those based at academic medical centers and/or major trauma centers, are far more engaged in complex reconstruction procedures on a day-to-day basis than cosmetic surgeons. We are intimately involved in preventing and treating face and tissue scarring, treating burns, and handling sensitive nerve-related injuries, some of which can be best served by having plastic surgeons on the scene or at least near the front lines where disaster victims are being evacuated.”

Examining the on-site evidence of several disasters, the authors identified four pivotal areas in trauma care where plastic surgeons have added expertise:

* soft tissue trauma;

* upper and lower extremity trauma;

* facial trauma; and

* burn management.

The authors suggest that plastic surgeons should be among those who help plan for medical responses prior to disasters, as well part of the responders working in conjunction with traditional surgical responders, such as trauma and orthopedic surgeons.

The authors examined responses reported in disaster events ranging from devastating earthquakes in Turkey and the London Underground bombings to the Sept. 11 attacks on the East Coast and found a substantial volume of overall cases involving plastic surgery-related issues.

In the case of the London bombings in 2005, facial fractures affected 18 percent of patients. In the Turkey earthquake in 1999, more than 13 percent of hospital beds were occupied by patients needing plastic surgery. In New York City, only 26 percent of burn victims were correctly triaged first to a burn center, despite there being an adequate number of dedicated burn beds in the area.

“Not only should such expert plastic surgeons become part of the disaster preparation team and actual response to applicable incidents, but their training curricula should now also include formal courses in disaster life support and incident command system management,” said Dr. Paul Pepe, chief of emergency medicine at UT Southwestern and an international expert in disaster management. “In essence, both disaster managers and plastic surgery program directors need to foster the contributions of this previously overlooked resource for dealing with catastrophic events.”

Soft tissue injuries, for example, are the most common acute injury from casualties resulting from a blast or explosion and can be treated by other specialties, according to the article. Early intervention by plastic surgeons, however, could help avert problems such as long-term scarring or wound healing and closure, and could be more cost effective.

“Plastic surgeons routinely deal with facial healing, facial fractures, tissue damage and related territory, making access to the expertise of a plastic surgeon invaluable,” Dr. Rohrich said.

Plastic surgeons also bring expertise in tissue viability, amputation and microcirculation issues that can affect whether limbs are preserved, the authors said. Similarly, plastic surgeons have routine experience with burn care that could be invaluable in the case of radiation, biological or fire disasters, as well as help in triaging patients. While other surgical specialists have degrees of expertise in such areas, having direct access to plastic surgeons would be an important asset to disaster medical relief teams.

“As many disciplines gather together to partner in disaster response and preparation, the plastic surgeons should be seen as pivotal members, let alone additional assets, for the medical casualty care team,” the study’s authors concluded.

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On the Net:

• UT Southwestern Medical Center
• Plastic and Reconstructive Surgery

Studies link improvements in diabetes control to frequency of use and demonstrate continued improvements 12 months after use, with ‘remarkably low’ occurrence of severe hypoglycemia

The latest data from groundbreaking human clinical trials of the effectiveness of continuous glucose monitors (CGM) show that the primary determinant of improvements in achieving better diabetes control is regular use of monitors ““ six days per week or more ““ rather than the age of patients, and that benefits continue well past the time when people with type 1 diabetes begin using the devices ““ including experiencing fewer low blood sugar emergencies.

The findings of two studies from the major multi-center trial funded by the Juvenile Diabetes Research Foundation were published online by the journal Diabetes Care (available at http://care.diabetesjournals.org/papbyrecent.shtml). The first showed that regular use of CGM devices is the principal factor in achieving better diabetes control, rather than the age of people using the monitors, or other demographic, clinical, or psychosocial factors. The second showed that people using CGM to help manage their disease were able to sustain good diabetes control; and just as important, that continued strong control came while actually lowering the incidence of hypoglycemia ““ dangerous low-blood-sugar incidents that can occur with tightly managed type1 diabetes.

“Based on these results and previous JDRF CGM trials published over the past 12 months, we know that these devices can help people get in control of their diabetes, help people already managing their disease maintain good control, and help people stay in control over an extended period of time, while lowering their risk for hypoglycemia,” said Dr. William V. Tamborlane, of Yale University, a co-chair of the JDRF funded study.

Research has shown that good blood sugar control is a key factor in reducing the risk of the devastating long-term complications of the disease, such as blindness and kidney disease ““ but that the fear of low blood sugar emergencies often prevents many people from achieving tight control, and remains a constant concern for those who manage their diabetes well. The landmark Diabetes Control and Complications Trial (DCCT) showed that with intensive insulin therapy, excellent blood glucose control was obtained, but at the expense of a considerable increase in hypoglycemia. Today, the JDRF study has shown that, with CGM, hypoglycemia can be reduced while maintaining excellent blood sugar control over an extended period of time.

The JDRF CGM study was a randomized and controlled trial involving 451 adults and children ranging in age from 8 to 72-years-old at 10 sites, including the Atlanta Diabetes Associates, the Joslin Diabetes Center, Kaiser Permanente Southern California, Nemours Children’s Clinic ““ Jacksonville, FL, the Lucile Packard Children’s Hospital at Stanford University, the Barbara Davis Center for Childhood Diabetes at the University of Colorado Denver, the University of Iowa, the University of Washington, and Yale University, and coordinated by the Jaeb Center for Health Research in Tampa, Florida. Three age groups were analyzed separately: 8 to 14 years of age, 15 to 24 years of age, and 25 years of age or older.

People with diabetes try to maintain their blood sugar levels between 70 mg/dL and 180 mg/dL. When blood sugar becomes very low, people can become confused, lethargic, and even slip into a coma or die. Very high blood sugars can also be dangerous. And long-term, lack of control increases the risk of developing devastating complications, including eye, kidney, nerve, and heart disease. One measure of control is HbA1c, which measures long-term blood sugar management; standards of good control are generally below 7% for adults, and below 7.5% to 8% for children, depending on age. Based on the DCCT findings, with respect to worsening of eye disease, a 10% decrease in HbA1c (7.2% vs. 8%) is associated with a 40% decrease in progression

According to one Diabetes Care paper (Factors Predictive of Use and of Benefit from CGM in Type 1 Diabetes), in the first six months of the JDRF trial, more frequent CGM use was associated with a greater reductions in HbA1c levels ““ a finding that was present in all age groups using the devices. Successful use of the devices was defined as an average of six days or more per week.

In each age group, patients averaging at least six days per week of CGM use had substantially greater improvements in HbA1c compared with those who used the devices less often.

According to the Jaeb Center’s Dr. Roy W. Beck, the initial findings published from the JDRF CGM trials in the New England Journal of Medicine in October 2008, had noted that improvements in diabetes control for participants in the trial were most significant among those in the 25 and older age group; children, teenagers and young adults saw less dramatic improvements. However, he pointed out, the findings published in Diabetes Care, looking at those same trial results in a different way, show that after adjusting for the frequency of CGM use, the association of age group with improvements in HbA1c was no longer significant ““ in other words, participants in the trial in all age groups, from children through adults, who used CGM devices six days per week or more saw similar levels of improvement in their diabetes control. In addition, the study found that regular use of blood glucose testing prior to beginning CGM therapy was an excellent predictor of regular CGM use and thus of improvement in glucose control.

The second study published in Diabetes Care (Sustained Benefit of Continuous Glucose Monitoring on HbA1c, Glucose Profiles, and Hypoglycemia in Adults with Type 1 Diabetes) showed that CGM use had long-term impact: people who began the trial with HbA1c levels at 7% or above saw a reduction in HbA1c mainly in the first eight weeks of the study, and then remained relatively stable through the next 44 weeks; and for participants who began the trials with an HbA1c below 7%, they remained within that target range over the entire 12 months of the study.

“In this six-month extension to the trial, we found that most adults continued to use CGM almost every day, and had sustained benefits in diabetes control as measured by HbA1c levels and the amount of time blood sugar was in the target range,” said Dr. Aaron Kowalski, Program Director for Metabolic Control at JDRF. “These benefits persisted despite less intensive follow-up over the second half of the trial than the first, which was designed to approximate usual clinical practice.”

He noted that just as important as the persistence of control that CGM devices helped patients achieve was the remarkably low rate of severe hypoglycemic events during the second six months of the study. Severe hypoglycemic events ““ which required the assistance of another person or medical professional ““ were experienced by 10% of the study participants during the first six months of the trial, but only by 4% in the second six months. The rate of severe hypoglycemic events fell from 21.8 events per 100 person-years during the first six months to 7.1 events per 100 person-years during the second six months. The rate was not associated with the HbA1c level of the trial participants at the time the study began.

According to Dr. Tamborlane, an investigator in both the JDRF CGM Trial and DCCT trials, the rate of severe hypoglycemia in people using CGM devices during the second six months of the JDRF trial was markedly lower than in the Diabetes Control and Complications Trial intensive treatment group ““ seven hypoglycemia events compared with 62 in the DCCT trial ““ even though the mean HbA1c of JDRF trial participants at 6.8% was lower than the DCCT trial participants’ level of 7.1%.

“Plus, the total absence of severe hypoglycemia during the second six months of the study in the participants who began the trial with an HbA1c below 7% is particularly striking, especially since these subjects were able to maintain a mean HbA1c of 6.4%,” Dr. Tamborlane said.

These studies are the third and fourth publications resulting from JDRF’s groundbreaking CGM trials, established to clinically assess the benefits of CGM devices in helping people with type 1 diabetes manage their disease more effectively. In addition to results published last fall in The New England Journal of Medicine, results were published in May in Diabetes Care, showing that people with type 1 diabetes who have already been successful in achieving recommended blood sugar goals (below 7%) can further benefit from using continuous glucose monitoring (CGM) devices, while experiencing less hypoglycemia.

JDRF has actively shared the results of the CGM trial with health insurance plans, and as a result many of the nation’s leading plans including Aetna, Cigna, Kaiser Permanente, United Healthcare, and Wellpoint now cover CGM for patients with type 1 diabetes. In addition, due to the JDRF trial, CGM is now included in national standards of care for type 1 diabetes, making doctors more likely to prescribe them for patients.

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On the Net:

• Juvenile Diabetes Research Foundation International
• More information on the JDRF CGM Trials, and on the Artificial Pancreas Project, is available online at http://www.artificialpancreas.org.

Hairstylists may have a unique opportunity to help steer their elderly clients to needed health services, according to a small, exploratory study.

More than 80 percent of 40 Columbus-area stylists surveyed said that older clients often or always shared their problems during appointments.

“Hair stylists are in a great position to notice when their older clients are starting to suffer from depression, dementia, or self-neglect,” said Keith Anderson, co-author of the study and assistant professor of social work at Ohio State University.

“While not expecting too much beyond the scope of their jobs, we may be able to help stylists direct elderly people in trouble to community services.”

Anderson conducted the study with Andrea Cimbal and Jeffrey Maile, graduate students in social work at Ohio State.  Their results appear in the current issue of the Journal of Applied Gerontology.

Anderson said he decided to do the study after reading sometimes-joking references in the popular press to “salon therapy,” in which clients discussed their relationship, family and health problems to their stylists, who act as sympathetic ears and sometimes as pseudo-therapists.

“I wondered if stylists really did have these close relationships with their clients,” Anderson said.

“And if they did, I thought there might be opportunities to use these relationships to help older adults.”

Anderson focused on older adults in this study because of his research interest in gerontology.

The study included 40 stylists from the Columbus area who responded to a mail survey.  The participants reported that, on average, about one-third of their clients were 60 years old or older.

Anderson said the results suggest that most stylists do develop close long-term relationships with their older clients.

About 85 percent of stylists described their relationships with older clients as “close” or “very close.”  About 72 percent said their role was like one of “family” to some of their older customers.

“This is one reason why I think hair stylists are especially suited to seeing problems in their customers,” Anderson said.

“Their older clients may sit in a chair for an hour or longer while they’re having their hair done, and this may happen once or twice a month.  So stylists are in a good position to recognize when things change with a client, and when they may need help.”

Health and family problems are the issues most often brought up by elderly customers ““ more than three-quarters of stylists have heard such complaints, the survey revealed.  And more than a third of stylists said clients have discussed problems with depression or anxiety.

The vast majority of stylists said their response to hearing their clients’ problems is to offer sympathy and support, and to try to cheer them up.

But fewer than half said they have given advice, and only about one-quarter have tried to get the client to speak to someone who can help them.

That’s not because they are not willing to help, Anderson said.  About two-thirds said they are willing to refer an older client to appropriate services.

But the problem, Anderson said, is that more than half ““ 52 percent — said they were not familiar with community services that may be helpful to older adults.

“It seems like a perfect setup ““ stylists have access to older adults who may need someone to point them to the help they need.  But at least this sample of stylists suggests they don’t know what services are out there to help these folks,” he said.

But could hairstylists identify older clients who needed professional help?

At least the stylists surveyed thought they could.  The researchers asked participants to rate on a scale of 1 to 10 (with 10 being the highest) their ability to recognize symptoms of depression, dementia and neglect in their older clients.  In all three cases, stylists rated their ability between 7.6 and 7.8.

Anderson said the question then becomes how to get stylists more involved in helping their older clients.  He noted that there’s already a national domestic violence awareness program called “Cut It Out” that recruits hair stylists to recognize indicators of domestic violence and get victims help.  Something similar could be done to assist older adults with mental health and related problems.

Anderson said he recognizes that stylists have a job to do, and can’t devote too much of their time and education to issues unrelated to hair styling.

Only 45 percent of the stylists surveyed said they were interested in receiving mental health training.

But stylists could play an important role by even just learning about local community services and offering brochures to older adults that have information on how to access the help they need.

“We can’t expect them to do everything, but our results suggest that most stylists care about their clients and would be willing to help them,” he said.

Written by Jeff Grabmeier – Ohio State University

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On the Net:

• Ohio State University
• Journal of Applied Gerontology
• “Cut It Out” Program