Drug companies paid big bucks to attend FDA painkiller meetings

Article by: Peter Whoriskey
Washington Post
October 6, 2013 – 11:15 PM

WASHINGTON – A scientific panel that shaped the federal government’s policy for testing the safety and effectiveness of painkillers was funded by major pharmaceutical companies that paid hundreds of thousands of dollars for the chance to affect the thinking of the Food and Drug Administration (FDA), according to hundreds of e-mails obtained by a public records request.

The e-mails show that the companies paid as much as $25,000 to attend any given meeting of the panel, which had been set up by two academics to provide advice to the FDA on how to weigh the evidence from clinical trials. A leading FDA official later called the group “an essential collaborative effort.”

Patient advocacy groups said the electronic communications suggest that the regulators had become too close to the companies trying to crack into the $9 billion painkiller market in the United States.

FDA officials who regulate painkillers sat on the steering committee of the panel, which met in private, and cowrote papers with employees of pharmaceutical companies.

The FDA has been criticized for not taking precautions that might have averted the epidemic of addiction to prescription drugs including OxyContin and other opioids.

“These e-mails help explain the disastrous decisions the FDA’s analgesic division has made over the last 10 years,” said Craig Mayton, the Columbus, Ohio, attorney who made the public records request to the University of Washington. “Instead of protecting the public health, the FDA has been allowing the drug companies to pay for a seat at a small table where all the rules were written.”

Even as the meetings were taking place, the idea of FDA officials meeting with firms that had paid big money for an invitation raised eyebrows for some. In an e-mail to organizers, an official from the National Institutes of Health worried whether the arrangements made it look as if the private meetings were a “pay to play process.”

FDA officials did not benefit financially from their participation in the meetings, the agency said. But two later went on to work as pharmaceutical consultants and more than this, the critics said, the e-mails portray an agency that, by allowing itself to get caught up in a panel that seemed to promise influence for money, had blurred the line between the regulators and the regulated.

In a statement, the FDA said “we take these concerns very seriously.” But, it said, “we are unaware of any improprieties” associated with the group.

http://www.startribune.com/business/226694611.html

Large HIV study stopped after safety review found more study participants who received the vaccine later became infected

HIV vaccine study halted by US government over unsuccessful shots

Associated Press in Washington

guardian.co.uk, Thursday 25 April 2013 17.52 EDT

A pharmaceutical machine loaded with ARV medicine at the Themba Lethu HIV/Aids clinic, Johannesburg

A 2009 study in Thailand is the only HIV/Aids study ever to show a modest success. Photograph: Denis Farrell/AP

The US government halted a large HIV vaccine study on Thursday, saying the experimental shots were not successful in preventing infection.

Nor did the shots reduce the amount of the Aids virus in the blood when people who had been vaccinated later became infected, the National Institutes of Health said.

“It’s disappointing,” said Dr Anthony Fauci, head of NIH’s National Institute of Allergy and Infectious Diseases. But he said there was “important information” gained from the study that will help determine what to try next.

The study had enrolled 2,504 volunteers, mostly gay men, in 19 cities since 2009. Half received dummy shots, and half received a two-part experimental vaccine developed by the NIH. All were provided free condoms and given extensive counseling about the risks of HIV.

It’s a strategy known as “prime-boost”. A DNA-based vaccine made with genetically engineered HIV material is given to prime the immune system to attack the Aids virus. Then a different vaccine, encasing the same material inside a shell made of a disabled cold virus, acts as a booster shot to strengthen that response. Neither vaccine could cause HIV.

The idea was to train immune cells known as T cells to spot and attack the very earliest HIV-infected cells in someone’s body. The hope was that the vaccine could either prevent HIV infection, or help those infected anyway to fight it.

A safety review this week found that slightly more study participants who had received the vaccine later became infected with HIV. It’s not clear why. But the difference wasn’t statistically significant, meaning it may be due to chance. Overall, there were 41 HIV infections in the vaccinated group and 30 among placebo recipients. When researchers examined only participants diagnosed after being in the study for at least 28 weeks – long enough for the shots to have done their job – there were 27 HIV infections among the vaccinated and 21 among the placebo recipients.

The NIH said Thursday that it is stopping vaccinations in the study, known as HVTN 505, but that researchers will continue to study the volunteers’ health.

Josh Robbins, 30, of Nashville, Tennessee, was one of the participants who became infected with HIV. He said he was glad he had taken part because its close monitoring meant he was diagnosed and treated much sooner than most people.

“We’ve got to keep moving forward,” Robbins said. The study “certainly can lead us down a new direction to hopefully find something that might work.”

Multiple attempts at creating an Aids vaccine have failed over the years. A 2009 study in Thailand is the only one ever to show a modest success, using a somewhat different prime-boost approach. Newer research suggests another approach – to try creating powerful antibodies that could work a step earlier than the T-cell attack, before HIV gets inside the first cell.

Both approaches need continued research funding, said Mitchell Warren of the international Aids Vaccine Advocacy Coalition. “Clearly an Aids vaccine remains critical,” he said.

http://www.guardian.co.uk/society/2013/apr/25/hiv-aids-vaccine-study-us-government

Repeated antibiotic use alters gut’s composition of beneficial microbes, Stanford study shows

2010 study posted for filing

Contact: Bruce Goldman goldmanb@stanford.edu 650-725-2106 Stanford University Medical Center

STANFORD, Calif. – Repeated use of an antibiotic that is considered generally benign, because users seldom incur obvious side effects, induces cumulative and persistent changes in the composition of the beneficial microbial species inhabiting the human gut, researchers at the Stanford University School of Medicine have found.

By a conservative estimate, something like 1,000 different varieties of microbes coexist harmoniously within a typical healthy person’s gut, said David Relman, MD, professor of medicine and of microbiology and immunology at the medical school and chief of the infectious diseases division at the Veterans Affairs Palo Alto Health Care System. Relman is the senior author of a paper, which will appear online Sept. 13 in Proceedings of the National Academy of Sciences.

The study examined the effects of ciprofloxacin (trade name Cipro), an antibiotic that is widely prescribed for intestinal, urinary and a variety of systemic infections. In an earlier, short-term study, Relman’s group had concluded that people’s intestinal microbial communities seem to bounce back reasonably well within weeks after a five-day regimen of ciprofloxacin. This new study involved two courses of antibiotic administration, six months apart, and it revealed more-subtle, long-term effects of ciprofloxacin use – such as the replacement of multiple resident bacterial species by other, closely related varieties and the occasional complete eradication of a species.

The infrequent occurrence of easily visible side effects such as bloating and diarrhea from ciprofloxacin use has given rise to an assumption that the drug spares most beneficial gut-dwelling bacteria. Overall similarities between pre-regimen gut bacterial strains and their post-regimen replacements explain why such side effects aren’t typically seen after ciprofloxacin use. Still, the more nuanced differences between the pre-existing communities and those that appear in the wake of this repeated disturbance present a new set of problems, said Relman, who is also the Thomas C. and Joan M. Merigan Professor at the medical school. A bacterial species whose presence was lost or diminished may have been performing a valuable job – for example, secreting a protein that’s toxic to a particular pathogen – that is shirked by its replacement. The abandoned function might not be noticed until, perhaps, years later when the pathogen in question invaded the person’s gut.

While the study’s findings shouldn’t be interpreted to mean that ciprofloxacin is dangerous and should be avoided, Relman said, they do raise questions about possible long-term effects of antibiotic administration, in addition to concerns about spurring the evolution of drug-resistant organisms. The new findings underscore the desirability of finding ways to pinpoint not just which bacteria have been lost or whose numbers were diminished by an antibiotic, but also which important beneficial functions performed by the patient’s gut microbial community as a whole have been impaired – such as signaling cells of the intestinal lining, which are constantly turning over, to maintain an appropriate barrier against ingested toxic compounds, or secreting anti-inflammatory substances that may prevent allergic or autoimmune diseases.

For this study, the Stanford scientists collected more than 50 stool samples from each of three healthy adult females over a period of 10 months. Then they used advanced, molecular techniques to count the number of different microbial species represented in each sample, as well as relative population sizes of the different species in that sample.

Twice during this 10-month period, the researchers perturbed their subjects’ gut ecosystems by giving them five-day courses of ciprofloxacin at a standard dose. During the first course, overall bacterial populations in each subject – which had previously waxed and waned but, on the whole, been quite stable – plummeted and remained depressed for about a week. Roughly one-third to one-half of the resident species’ populations declined, with some disappearing entirely. A few originally less-abundant species grew in number, as they filled in the ecological niche abandoned by bugs adversely affected by the drug.

Within a week after the first course’s completion, two of the three subjects’ internal microbial ecosystems had largely returned to a state fairly similar to that before the regimen, as measured by the broad classes to which the microbial constituents belonged. One subject’s overall ecosystem, however, still had not recovered even by that rough measure a full six months later.

The second course of antibiotic administration produced a stronger effect. “Even the one subject whose gut bacterial community fully recovered after the first ciprofloxacin course experienced an incomplete recovery after the second one,” said Relman. The communities in the other two subjects partially recovered from the second course, but never returned to their original state. In essence, each subject’s community of gut-dwelling microbes shifted to a new, “alternative” state and remained in that state for at least two months after the second antibiotic course had been completed. Thus, all three subjects experienced significant and lasting changes in the specific membership of their internal microbial communities at the end of the 10-month study period.

“Ecologists have found that an ecosystem, such as a wildlife refuge, that is quite capable of rebounding from even huge occasional perturbations – forest fire, volcanic eruption, pests – may yet be undone by too rapid a series of such perturbations,” said Les Dethlefsen, PhD, a research scientist in Relman’s lab and the study’s first author. “In the same way, recurring antibiotic use may produce a cumulative effect on our internal microbial ecosystems with potentially debilitating, if as yet unpredictable, consequences.”

“It’s as if your beneficial bacteria ‘remember’ the bad things done to them in the past,” said Relman. “Clinical signs and symptoms may be the last thing to show up.”

The precise counts of gut-dwelling microbes in this study were made possible by a new technique, pioneered in recent years by Relman and others. The older method – growing the microbes in culture – simply doesn’t work for many species and, even when it does, rare species are often swamped by more common ones and don’t get counted. The new technique reads short, telltale DNA snippets that distinguish microbes both from human cells and one from another. This allowed the Stanford researchers to assess both the total number of different microbial varieties and the relative size of each variety’s population.

Similar techniques now make it possible to assess, before and after antibiotic administration, the abundance in a patient’s gut of microbial genes known to code for important functions performed by one or more members of the patient’s gut community, Relman said. In the future, if it becomes known that a key function has been impaired, clinicians might perhaps restore that function by prescribing specific probiotics or nutrients that encourage the return of appropriate beneficial bugs.

###

The research was supported by a National Institutes of Health Pioneer Award and by the Doris Duke Charitable Foundation. More information about the Departments of Medicine and of Microbiology and Immunology, which also supported the research, is available at http://medicine.stanford.edu and http://microimmuno.stanford.edu.

The Stanford University School of Medicine consistently ranks among the nation’s top medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://mednews.stanford.edu. The medical school is part of Stanford Medicine, which includes Stanford Hospital & Clinics and Lucile Packard Children’s Hospital. For information about all three, please visit http://stanfordmedicine.org/about/news.html.

Xenical and Alli, inhibits a key enzyme that may lead to “severe toxicity of internal organs such as the liver and kidney.” The inhibition is irreversible and can be caused by a low level of the drug.

Contact: Dave Lavallee dlavallee@advance.uri.edu 401-874-5862 University of Rhode Island

Pharmacy researcher finds most popular weight-loss drug strongly alters other drug therapies

KINGSTON, R.I.— December 10, 2012 – A University of Rhode Island researcher has discovered that the weight-loss drug orlistat, known by the brand names Xenical and Alli, inhibits a key enzyme that may lead to “severe toxicity of internal organs such as the liver and kidney.” The inhibition is irreversible and can be caused by a low level of the drug.

Professor Bingfang Yan’s study funded by the National Institutes of Health, also found that the drug alters efficacy of medicines, and particularly limits the effectiveness of some anti-cancer drugs.

Part of the research results will be published in the journal, Biochemical Pharmacology, which has the article posted on its website today. Yan also alerted the U.S. Food and Drug Administration to his findings.

Orlistat, which was originally approved by the FDA in 1999 as the prescription drug Exenical, was approved in 2007 as the over-the-counter medication Alli. It has been the most commonly used medicine to treat obesity for more than a decade, Yan said.

“Since it has been available over–the-counter, there has been a drastic increase of toxicity among patients using the drug,” Yan said. “It has been linked to severe liver failure, acute pancreatic failure and acute renal (kidney) failure.”

Yan said orlistat works in the intestinal tract by preventing fat from being absorbed by the body. It is generally accepted that orlistat remains in the intestine and that the body does not absorb it.

“But orlistat is reportedly absorbed, and certainly internal organs such as the liver and kidney are exposed to this drug upon absorption,” he said.

The study showed that the drug is a potent inhibitor of carboxylesterase-2, which is a major detoxification enzyme in the liver, kidney and gastrointestinal track. “When the activity of this enzyme drop in those organs, toxicity increases or the efficacy of some drugs are altered,” Yan said.

The enzyme is known to metabolize a wide range of medicines including aspirin and the cancer drugs irinotecan and pentyl carbamate of p-aminobenzyl carbamate of doxazolidine.

“This study shows that orlistat profoundly alters the therapeutic potential of the anti-cancer drugs,” Yan said. “In the case of the anti-cancer drugs, it weakens their effectiveness.”

Prior or co-presence of orlistat with one of the anti-cancer drugs resulted in cancer cells being far more prolific.

“Alli-based interactions can be key factors in the efficacy of medicines,” Yan said.

Yan was also interested in Alli’s effects on aspirin and its use as a blood thinner. “Aspirin is used to treat blood clots. Yan predicated: “Orlistat would increase the therapeutic potential of aspirin, which may increase the tendency of bleeding.”

This isn’t the first time that Yan has found critical drug interactions in his studies.

In 2006, he discovered that the anti-viral drug Tamiflu would be rendered ineffective in patients also taking the anti-clotting drug Plavix. His published findings have resulted in new dosing regimens for patients who need both drugs.

Yan is one of the authors of the 6-volume Encyclopedia of Drug Metabolism and Interactions. This state-of-the-art integrated reference represents a global effort and presents more than 120 chapters by prominent authors from 11 different countries: the United States, Canada, United Kingdom, Germany, Australia, Singapore, India, Japan, France, Denmark, and Switzerland.

Exposure to 3 classes of common chemicals may affect female development

2010 study posted for filing

Contact: Mount Sinai Press Office newsnow@mountsinai.org 212-241-9200 The Mount Sinai Hospital / Mount Sinai School of Medicine

Researchers at Mount Sinai School of Medicine have found that exposure to three common chemical classes—phenols, phthalates and phytoestrogens—in young girls may disrupt the timing of pubertal development, and put girls at risk for health complications later in life. The study, the first to examine the effects of these chemicals on pubertal development, is currently published online in the journal Environmental Health Perspectives.

“Research has shown that early pubertal development in girls can have adverse social and medical effects, including cancer and diabetes later in life,” said Dr. Mary Wolff, Professor of Preventive Medicine and Oncological Sciences at Mount Sinai School of Medicine. “Our research shows a connection between chemicals that girls are exposed to on a daily basis and either delayed or early development. While more research is needed, these data are an important first step in continuing to evaluate the impact of these common environmental agents in putting girls at risk.”

Phenols, phthalates and phytoestrogens are among chemicals known as endocrine disruptors, which interfere with the body’s endocrine, or hormone, system. They are found in a wide range of consumer products, such as nail polishes, where they increase durability, and in cosmetics, perfumes, lotions, and shampoos, where they carry fragrance. Some are used to increase the flexibility and durability of plastics such as PVC, or are included as coatings on medications or nutritional supplements to make them timed-release.

Dr. Wolff, co-principal investigator Susan Teitelbaum, PhD, Associate Professor, Preventive Medicine, and their team from Mount Sinai’s departments of Pediatrics and Microbiology recruited girls from the neighborhood of East Harlem, a unique minority population considered high risk. Working with Cincinnati Children’s Hospital and Kaiser Permanente Northern California, they analyzed the impact of exposure to environmental agents in a study that included 1,151 girls from New York, greater Cincinnati and northern California.

The girls were between 6- and 8-years-old at enrollment and between 7 and 9 at analysis. Researchers collected urine samples from the study participants and analyzed them for phenols, phthalates, and phytoestrogens, including 19 separate urine biomarkers.

The data showed that the three classes of chemical compounds were widely detectable in the study population, and that high exposure to certain chemicals was associated with early breast development. The strongest links were seen with phthalates and phytoestrogens, which were also among the highest exposures. One phenol, two phytoestrogens, and a subset of phthalates (those found in building products and plastic tubing) were associated with later puberty. However, the phthalates found in personal products such as lotion and shampoo, especially those with fragrance, were related to earlier breast and pubic hair development.

“We believe that there are certain periods of vulnerability in the development of the mammary gland, and exposure to these chemicals may influence breast cancer risk in adulthood,” Dr. Wolff continued. “Dietary habits may also have an impact. Further study is needed to determine how strong the link is.”

Consistent with previous studies, researchers also found that body-mass index (BMI) played a role in the onset of puberty. About a third of the girls were considered overweight, which is also an indicator of early breast development. As a result, some of the chemical associations differed in more or less obese girls. Researchers continue to study the impact of diet on pubertal development and eventual breast cancer risk.

“Exposure to these chemicals is extremely common,” Dr. Wolff continued. “As such, while the association between chemicals and pubertal development seems small, the impact on the overall population is significant.”

###

Funding for the research was provided by a grant from the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health (NIH). The data is published on Environmental Health Perspectives online at http://ehp03.niehs.nih.gov/article/fetchArticle.action?articleURI=info%3Adoi%2F10.1289%2Fehp.0901690.

About The Mount Sinai Medical Center

The Mount Sinai Medical Center encompasses The Mount Sinai Hospital and Mount Sinai School of Medicine. The Mount Sinai Hospital is one of the nation’s oldest, largest and most-respected voluntary hospitals. Founded in 1852, Mount Sinai today is a 1,171-bed tertiary-care teaching facility that is internationally acclaimed for excellence in clinical care. Last year, nearly 60,000 people were treated at Mount Sinai as inpatients, and there were nearly 450,000 outpatient visits to the Medical Center.

Mount Sinai School of Medicine is internationally recognized as a leader in groundbreaking clinical and basic science research, as well as having an innovative approach to medical education. With a faculty of more than 3,400 in 38 clinical and basic science departments and centers, Mount Sinai ranks among the top 20 medical schools in receipt of National Institute of Health (NIH) grants. For more information, please visit www.mountsinai.org.

Study Shows Common Pain Cream Could Protect Heart During Attack: 85 percent reduction in cardiac cell death

2009 study posted for filing

Study Shows Common Pain Cream Could Protect Heart During Attack

CINCINNATI—New research from the University of Cincinnati shows that a common, over-the-counter pain salve rubbed on the skin during a heart attack could serve as a cardiac-protectant, preventing or reducing damage to the heart while interventions are administered.

These findings are published in the Sept. 14 edition of the journal Circulation.

Keith Jones, PhD, a researcher in the department of pharmacology and cell biophysics, and scientists in his lab have found that applying capsaicin to specific skin locations in mice caused sensory nerves in the skin to trigger signals in the nervous system. These signals activate cellular “pro-survival” pathways in the heart which protect the muscle.

Capsaicin is the main component of chili peppers and produces a hot sensation. It is also the active ingredient in several topical medications used for temporary pain relief.

Capsaicin is approved for use by the U.S. Food and Drug Administration.

Jones is working with Neal Weintraub, MD, a UC Health cardiologist and director of UC’s cardiovascular diseases division, and other clinicians to construct a translational plan to test capsaicin in a human population.

“Topical capsaicin has no known serious adverse effects and could be easily applied in an ambulance or emergency room setting well in advance of coronary tissue death,” Jones says. “If proven effective in humans, this therapy has the potential to reduce injury and/or death in the event of a coronary blockage, thereby reducing the extent and consequences of heart attack.”

Researchers observed an 85 percent reduction in cardiac cell death when capsaicin was used.

They also found that a small incision made on the abdomen triggered an 81 percent reduction.

“Both this and the capsaicin effect are shown to work through similar neurological mechanisms,” Jones says. “These are the most powerful cardioprotective effects recorded to date.

“This is a form of remote cardioprotection, using a skin stimulus that activates cardioprotection long before the blocked coronary artery is opened.”

Weintraub adds that this finding offers an important distinction between existing therapies.

“All of the current interventions require the vessel to be opened before doctors can act, and since it takes time to elicit protection, tissue dies,” he says. “This treatment will protect the heart before the vessel is opened while producing a strong protective effect that is already active when we open the vessel.”

Jones and Weintraub think that skin—the main sensor and largest human body organ—has evolved to protect animals, including humans, in a variety of ways.

“By activating these sensors in the nervous system, via skin, we think that a response to preserve and protect the heart is triggered,” Weintraub says.

“We think that this technique is fooling the body into sending out protective signals,” Jones adds. “This may be similar to the way certain acupuncture treatments work; there may be a neurological basis. In a broad sense, this work may provide a ‘Rosetta stone’ for translating alternative medicine techniques—like acupuncture—to Western medicine. Perhaps we can understand the biological mechanisms of how alternative treatments may be successful for patients.”

Now, researchers will further explore this concept by investigating which sensors are associated with certain aspects of organ protection—and how much of specific stimuli are needed to produce the desired responses.

“This could help create favorable outcomes for those who are experiencing stroke, shock or are in need of an organ transplant, and the best part is that it is done non-invasively and is relatively inexpensive,” Jones says.

But he warns against rubbing capsaicin on your belly if you feel like you are having a heart attack.

“We don’t know if it will work for all indications, for all patients, and we don’t know if it will work over an extended amount of time,” he says. “A major goal is testing this therapy in clinical trials, but we still need to study more about dosage and application—where we put it on the body for the best results. However, this has tremendous clinical potential and could eventually save lives.”

This study was funded by the National Institutes of Health and by the University of Cincinnati. Jones and Weintraub have filed a patent for this funding but have received no honoraria from the makers of capsaicin.

Mount Sinai School of Medicine study shows vitamin C prevents bone loss in animal models

Contact: Jeanne Bernard Jeanne.Bernard@mountsinai.org 212-241-9200 The Mount Sinai Hospital / Mount Sinai School of Medicine

Researchers at Mount Sinai School of Medicine have shown for the first time in an animal model that vitamin C actively protects against osteoporosis, a disease affecting large numbers of elderly women and men in which bones become brittle and can fracture. The findings are published in the October 8 online edition of PLoS ONE.

“This study has profound public health implications, and is well worth exploring for its therapeutic potential in people,” said lead researcher Mone Zaidi, MD, Professor of Medicine (Endocrinology, Diabetes and Bone Disease, and of Structural and Chemical Biology, and Director of the Mount Sinai Bone Program.

“The medical world has known for some time that low amounts of vitamin C can cause scurvy and brittle bones, and that higher vitamin C intake is associated with higher bone mass in humans, “said Dr. Zaidi. “What this study shows is that large doses of vitamin C, when ingested orally by mice, actively stimulate bone formation to protect the skeleton. It does this by inducing osteoblasts, or premature bone cells, to differentiate into mature, mineralizing specialty cells.”

The researchers worked with groups of mice whose ovaries had been removed, a procedure known to reduce bone density, and compared them with control mice that had “sham” operations, which left their ovaries intact. The mice with ovariectomies were divided into two groups, one of which was given large doses of vitamin C over eight weeks. The scientists measured the bone mineral density in the lumbar spine, femur, and tibia bones.

The mice who received an ovariectomy – and no vitamin C — had a much lower bone mineral density (BMD) versus controls, whereas mice who received a ovariectomy and large doses of vitamin C, had roughly the same BMD as the controls, suggesting vitamin C prevented BMD loss in this group.

“Further research may discover that dietary supplements may help prevent osteoporosis in humans,” said Dr. Zaidi. “If so, the findings could be ultimately useful to developing nations where osteoporosis is prevalent and standard medications are sparse and expensive.”

###

About The Mount Sinai Medical Center

The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Mount Sinai School of Medicine. Established in 1968, Mount Sinai School of Medicine is one of the leading medical schools in the United States. The Medical School is noted for innovation in education, biomedical research, clinical care delivery, and local and global community service. It has more than 3,400 faculty in 32 departments and 14 research institutes, and ranks among the top 20 medical schools both in National Institutes of Health (NIH) funding and by U.S. News & World Report.

The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation’s oldest, largest and most-respected voluntary hospitals. In 2012, U.S. News & World Report ranked The Mount Sinai Hospital 14th on its elite Honor Roll of the nation’s top hospitals based on reputation, safety, and other patient-care factors. Mount Sinai is one of 12 integrated academic medical centers whose medical school ranks among the top 20 in NIH funding and by U.S. News & World Report and whose hospital is on the U.S. News & World Report Honor Roll. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 560,000 outpatient visits took place.

For more information, visit http://www.mountsinai.org/.

Find Mount Sinai on:

Facebook: http://www.facebook.com/mountsinainyc Twitter @mountsinainyc YouTube: http://www.youtube.com/mountsinainy

Survivors of 1918 flu pandemic protected with a lifetime immunity to virus

Contact: Mount Sinai Newsroom
newsmedia@mssm.edu
212-241-9200
The Mount Sinai Hospital / Mount Sinai School of Medicine

New research has discovered that infection and natural exposure to the 1918 influenza virus made survivors immune to the disease for the remaining of their lives. Antibodies produced by cells isolated from these survivors served as an effective therapy to protect mice from the highly lethal 1918 infection. The study entitled “Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors,” was released for advanced online publication by the journal Nature. Researchers at Mount Sinai School of Medicine’s Department of Microbiology contributed to the research findings. An estimated 50 million people were killed by the 1918 flu pandemic worldwide.

“Ninety years after survivors encountered the 1918 pandemic influenza virus, we collected antibody-producing B cells from them, and successfully isolated B cells that produce antibodies that block the viral infection,” said contributing author Dr. Christopher Basler, PhD, Associate Professor of Microbiology at Mount Sinai School of Medicine. “The antibodies produced by these cells demonstrated remarkable power to block 1918 flu virus infection in mice, proving that, even nine decades after infection with this virus, survivors retain protection from it.”

“The fact that you can isolate these anti-1918 memory B cells so long after infection will hopefully provide the impetus to further study the mechanisms behind long lived immunity,” said Dr. Osvaldo Martinez, post-doctoral fellow at Mount Sinai School of Medicine.

For this study, 32 individuals who were born before 1918 and lived through the influenza pandemic were recruited by Dr. Eric Altschuler at the University of Medicine and Dentistry of New Jersey to donate blood which was tested by Dr. Basler’s lab for the presence of antibodies that recognize the 1918 virus. Dr. James Crowe and colleagues at Vanderbilt University produced antibodies from these individuals’ blood cells and provided these to Dr. Basler’s lab where the potent neutralizing activity against 1918 virus was demonstrated. Antibodies were also provided to Dr. Terrence Tumpey at the CDC to test in mice the strength of the antibodies derived from the 1918 survivors.

“Our findings show that survivors of the pandemic have highly effective, virus neutralizing antibodies to this powerful virus, and humans can sustain circulating B memory cells to viruses for up to 9 decades after exposure,” said Dr. Tshidi Tsibane, post-doctoral fellow, Department of Microbiology, Mount Sinai School of Medicine. “These findings could serve as potential therapy for another 1918-like virus.”

###

Vanderbilt University, Mount Sinai School of Medicine, University of Medicine and Dentistry of New Jersey, Centers for Disease Control and Prevention and The Scripps Research Institute collaborated on this research study.

About The Mount Sinai Medical Center The Mount Sinai Medical Center encompasses The Mount Sinai Hospital and Mount Sinai School of Medicine. The Mount Sinai Hospital is one of the nation’s oldest, largest and most-respected voluntary hospitals. Founded in 1852, Mount Sinai today is a 1,171-bed tertiary-care teaching facility that is internationally acclaimed for excellence in clinical care. Last year, nearly 50,000 people were treated at Mount Sinai as inpatients, and there were nearly 450,000 outpatient visits to the Medical Center.

Mount Sinai School of Medicine is internationally recognized as a leader in groundbreaking clinical and basic-science research, as well as having an innovative approach to medical education. With a faculty of more than 3,400 in 38 clinical and basic science departments and centers, Mount Sinai ranks among the top 20 medical schools in receipt of National Institute of Health (NIH) grants

Vitamin C injections slow tumor growth in mice

Repost 2008

Contact: Joan Chamberlain niddkmedia@mail.nih.gov 301-496-3583 NIH/National Institute of Diabetes and Digestive and Kidney Diseases

High-dose injections of vitamin C, also known as ascorbate or ascorbic acid, reduced tumor weight and growth rate by about 50 percent in mouse models of brain, ovarian, and pancreatic cancers, researchers from the National Institutes of Health (NIH) report in the August 5, 2008, issue of the Proceedings of the National Academy of Sciences. The researchers traced ascorbate’s anti-cancer effect to the formation of hydrogen peroxide in the extracellular fluid surrounding the tumors. Normal cells were unaffected.

Natural physiologic controls precisely regulate the amount of ascorbate absorbed by the body when it is taken orally. “When you eat foods containing more than 200 milligrams of vitamin C a day–for example, 2 oranges and a serving of broccoli–your body prevents blood levels of ascorbate from exceeding a narrow range,” says Mark Levine, M.D., the study’s lead author and chief of the Molecular and Clinical Nutrition Section of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the NIH. To bypass these normal controls, NIH scientists injected ascorbate into the veins or abdominal cavities of rodents with aggressive brain, ovarian, and pancreatic tumors. By doing so, they were able to deliver high doses of ascorbate, up to 4 grams per kilogram of body weight daily. “At these high injected doses, we hoped to see drug-like activity that might be useful in cancer treatment,” said Levine.

Vitamin C plays a critical role in health, and a prolonged deficiency leads to scurvy and eventually to death. Some proteins known as enzymes, which have vital biochemical functions, require the vitamin to work properly. Vitamin C may also act as an antioxidant, protecting cells from the damaging effects of free radicals. The NIH researchers, however, tested the idea that ascorbate, when injected at high doses, may have prooxidant instead of antioxidant activity. Prooxidants would generate free radicals and the formation of hydrogen peroxide, which, the scientists hypothesized, might kill tumor cells. In their laboratory experiments on 43 cancer and 5 normal cell lines, the researchers discovered that high concentrations of ascorbate had anticancer effects in 75 percent of cancer cell lines tested, while sparing normal cells. In their paper, the researchers also showed that these high ascorbate concentrations could be achieved in people.

The team then tested ascorbate injections in immune-deficient mice with rapidly spreading ovarian, pancreatic, and glioblastoma (brain) tumors. The ascorbate injections reduced tumor growth and weight by 41 to 53 percent. In 30 percent of glioblastoma controls, the cancer had spread to other organs, but the ascorbate-treated animals had no signs of disseminated cancer. “These pre-clinical data provide the first firm basis for advancing pharmacologic ascorbate in cancer treatment in humans,” the researchers conclude.

Interest in vitamin C as a potential cancer therapy peaked about 30 years ago when case series data showed a possible benefit. In 1979 and 1985, however, other researchers reported no benefit for cancer patients taking high oral doses of vitamin C in two double-blind, placebo-controlled clinical trials.

Several observations led the NIH researchers to revisit ascorbate as a cancer therapy. “Clinical and pharmacokinetic studies conducted in the past 12 years showed that oral ascorbate levels in plasma and tissue are tightly controlled. In the case series, ascorbate was given orally and intravenously, but in the trials ascorbate was just given orally. It was not realized at the time that only injected ascorbate might deliver the concentrations needed to see an anti-tumor effect,” said Levine, who noted that new clinical trials of ascorbate as a cancer treatment are in the planning stages.

Data from Levine’s earlier studies of the regulation and absorption of dietary vitamin C were used in the revision of the Institute of Medicine’s Recommended Dietary Allowance for the vitamin in 2000. In the current study, Levine led a team of scientists from the NIDDK and the National Cancer Institute (NCI), both components of the NIH, as well as the University of Kansas. “NIH’s unique translational environment, where researchers can pursue intellectual high-risk, out-of-the-box thinking with high potential payoff, enabled us to pursue this work,” he said.

###

For more information about cancer, please visit the NCI website at www.cancer.gov, or call NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

The NIDDK conducts and supports research in diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition, and obesity; and kidney, urologic, and hematologic diseases. Spanning the full spectrum of medicine and afflicting people of all ages and ethnic groups, these diseases encompass some of the most common, severe, and disabling conditions affecting Americans. For more information about NIDDK and its programs, see www.niddk.nih.gov.

The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, see www.nih.gov.

Health-care costs at end of life exceed total assets for 25 percent of Medicare population: does not cover co-payments, deductibles, homecare services, or non-rehabilitative nursing home care

Contact: Jeanne Bernard Jeanne.Bernard@mountsinai.org 212-241-9200 The Mount Sinai Hospital / Mount Sinai School of Medicine

As many as a quarter of Medicare recipients spend more than the total value of their assets on out-of-pocket health care expenses during the last five years of their lives, according to researchers at Mount Sinai School of Medicine. They found that 43 percent of Medicare recipients spend more than their total assets minus the value of their primary residences. The findings appear online in the current issue of the Journal of General Internal Medicine.

The amount of spending varied with the patient’s illness. Those with dementia or Alzheimer’s disease spent the most for health care, averaging $66,155, or more than twice that of patients with gastrointestinal disease or cancer, who spent an average of $31,069. Dementia patients often require special living arrangements, which accounts for the sizeable difference in cost.

“Medicare provides a significant amount of health care coverage to people over 65, but it does not cover co-payments, deductibles, homecare services, or non-rehabilitative nursing home care,” said the study’s lead author, Amy S. Kelley, MD, Assistant Professor of Geriatrics and Palliative Medicine at Mount Sinai School of Medicine. “I think a lot of people will be surprised by how high these out-of-pocket costs are in the last years of life.”

The researchers based their findings on 2002-2008 data that was collected from the Health and Retirement Study, a biennial survey of 26,000 Americans over the age of 50, which is supported by the National Institute on Aging, and the Social Security Administration. They examined 3,209 Medicare recipients during their last five years of life, and compared their out-of-pocket health care expenditures with their total household assets. The study found that the average spending for all participants was $38,688, with more than 75 percent of households spending at least $10,000. The top quarter of participants spent an average of $101,791.

“There are a number of schools of thought on how to rein in Medicare costs, including requiring larger financial contributions from the elderly,” said Dr. Kelley. “Prior to this study there was not a lot of data on the extent of out-of-pocket spending. This information can serve as an important tool to help individuals set realistic expectations for end-of-life health care costs, and for government officials to use in discussing Medicare policies.”

###

This study was funded by the National Institute on Aging. Dr. Kelley also receives funding from the Hartford Foundation. Researchers from University of California Los Angeles Department of Economics, Dartmouth College Department of Economics, and The Dartmouth Institute for Health Policy and Clinical Practice also contributed to this study.

About The Mount Sinai Medical Center

The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation’s oldest, largest and most-respected voluntary hospitals. In 2012, U.S. News & World Report ranked The Mount Sinai Hospital 14th on its elite Honor Roll of the nation’s top hospitals based on reputation, safety, and other patient-care factors. Mount Sinai is one of 12 integrated academic medical centers whose medical school ranks among the top 20 in NIH funding and by U.S. News & World Report and whose hospital is on the U.S. News & World Report Honor Roll. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 560,000 outpatient visits took place.

La Jolla Institute unlocks mystery of potentially fatal reaction to smallpox vaccine

Contact: Bonnie Ward contact@liai.org 619-303-3160 La Jolla Institute for Allergy and Immunology

Research team is part of NIH network working toward new smallpox vaccine for eczema sufferers

SAN DIEGO – (May 25, 2009) Researchers from the La Jolla Institute for Allergy & Immunology have pinpointed the cellular defect that increases the likelihood, among eczema sufferers, of developing eczema vaccinatum, a severe and potentially fatal reaction to the smallpox vaccine. The research, conducted in mouse models, was funded under a special research network created by the National Institutes of Health in 2004. The network is working toward the development of a new smallpox vaccine that could be administered to the millions of Americans who suffer from atopic dermatitis, a chronic, itchy skin condition commonly referred to as eczema.

The La Jolla Institute’s Toshiaki and Yuko Kawakami, M.D.s, Ph.D.s., a husband and wife scientific team, led the research group which found that activity levels of Natural Killer (NK) cells played a pivotal role in the development of eczema vaccinatum in the mice. The activity of the NK cells, which are disease fighting cells of the immune system, was significantly lower in the mice that developed eczema vaccinatum than in normal mice that also received the smallpox vaccine. This knowledge opens the door to one day developing therapies that could potentially boost NK cell activity in eczema sufferers.

“Since atopic dermatitis affects as many as 17 percent of children in the U. S. and since eczema vaccinatum carries a fatality rate of 5-10 percent, therapies that prevent or treat eczema vaccinatum successfully are crucial should the need for mass vaccination against smallpox arise in response to bioterrorism,” said Harvard pediatrics professor Raif S. Geha, M.D., chief of immunology at Boston Children’s Hospital and a principal investigator in the NIH funded network investigating eczema vaccinatum. “The discovery of the Kawakami team, who are participants in the NIH network, is an important step towards this goal.”

People with active atopic dermatitis (eczema), or who have outgrown atopic dermatitis, and the people they live with currently cannot receive smallpox vaccinations because of the risk of eczema vaccinatum. While uncommon, eczema vaccinatum can develop when atopic dermatitis patients are given the smallpox vaccine or come into close personal contact with people who recently received the vaccine. It is estimated that a significant portion of the U.S. population is currently not eligible for smallpox vaccination.

“This discovery answers an important question that has long eluded the scientific community, “why people with atopic dermatitis were susceptible to developing eczema vaccinatum upon receiving the smallpox vaccine, while the general population was not,” said Mitchell Kronenberg, the La Jolla Institute’s president & scientific director. “It marks a significant advance toward the goal of ensuring that everyone can one day be protected against the smallpox virus.”

The finding was published today in the online version of the Journal of Experimental Medicine in a paper entitled, “Inhibition of NK cell activity by IL-17 allows vaccinia virus to induce severe skin lesions in a mouse model of eczema vaccinatum.” La Jolla Institute scientist Shane Crotty, Ph.D., also contributed to the study.

Regarded as the deadliest disease ever known to man, smallpox was officially eradicated worldwide in 1980 and routine vaccinations against the disease ended in the U.S in 1972. However, bioterrorism concerns have arisen over recent years regarding the deliberate distribution of the smallpox virus, which might make smallpox vaccinations once again necessary. Such concerns led to the creation of the Atopic Dermatitis and Vaccinia Network (ADVN), a consortium of medical and research institutions nationwide developed by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. The network, which provided grant funding for the Kawakami’s studies under NIH contact N01-AI40030C, was launched in 2004 with the goal of developing a new smallpox vaccine that would be safe for atopic dermatitis sufferers. It includes three consortiums, involving data, clinical testing and animal studies, of which Drs. Kawakami and the La Jolla Institute are members.

The Animal Studies Consortium was created to establish animal models of atopic dermatitis and investigate their immune responses to vaccinia — the virus used in smallpox vaccine. Drs. Kawakami were invited to join the consortium due to their creation of a new, more effective atopic dermatitis mouse model in 2004.

In their study, Drs. Kawakami showed that eczema-infected mice had higher levels of IL-17 cells, which are known to inhibit NK cell activity. “This higher level of IL-17 cells slowed down the ability of the NK cells to kill the vaccinia virus,” said Yuko Kawakami, noting people with atopic dermatitis are also known to have higher numbers of IL-17 producing cells. “This led to the development of eczema vaccinatum when these mice received the smallpox vaccine.”

Drs. Kawakami tested their theory by stimulating more NK cell activity in the eczema-infected mice. The higher activity led to the elimination of the eczema vaccinatum infection. “We are very excited by these findings, ” said Toshiaki Kawakami. “Developing a safer smallpox vaccine is the most important thing in this field.”

###

About La Jolla Institute

Founded in 1988, the La Jolla Institute for Allergy & Immunology is a nonprofit medical research center dedicated to increasing knowledge and improving human health through studies of the immune system. Scientists at the institute carry out research searching for cures for cancer, allergy and asthma, infectious diseases, and autoimmune diseases such as diabetes, inflammatory bowel disease and arthritis. La Jolla Institute’s research staff includes more than 100 Ph.Ds and M.D.s.

Reposted at request

Johns Hopkins team finds ICU misdiagnoses may account for as many annual deaths as breast cancer

Armstrong Institute researchers discover missed medical conditions in more than 1 in 4 critically ill adults

Each year as many as 40,500 critically ill U.S. hospital patients die with an unknown medical condition that may have caused or contributed to their death, Johns Hopkins patient safety experts report in a recent study.

In a discussion of their findings, described online in BMJ Quality & Safety, researchers say that although diagnostic errors in the intensive care unit (ICU) may claim as many lives each year as breast cancer, they remain an underappreciated cause of preventable patient harm.

“Our study shows that misdiagnosis is alarmingly common in the acute care setting,” says Bradford Winters, M.D., Ph.D., lead author and associate professor of anesthesiology and critical care medicine and neurology and surgery in the Johns Hopkins University School of Medicine. “To date, there’s been very little research to determine root causes or effective interventions,” Winters says, noting that less lethal patient safety risks have received greater attention.

By reviewing studies that used autopsy to detect diagnostic errors in adult ICU patients, the experts in the Johns Hopkins Armstrong Institute for Patient Safety and Quality discovered that 28 percent of patients — more than one in four — had at least one missed diagnosis at death. In 8 percent of patients, the diagnostic error was serious enough that it may either have caused or directly contributed to the individual’s death and, if known, likely would have changed treatment, researchers say. Infections and vascular maladies, such as heart attack and stroke, accounted for more than three-quarters of those fatal flaws.

Overall, the medical conditions most commonly missed by diagnosticians included heart attack; pulmonary embolism, an artery blockage in the lungs; pneumonia; and aspergillosis, a fungal infection that most commonly affects individuals with a weakened immune system. Cumulatively, these four conditions accounted for about one-third of all illnesses that doctors failed to detect.

Their review of 31 studies included 5,863 autopsies from a wide range of ICU types. The prevalence of autopsy-detected misdiagnoses, which were stratified by severity, ranged from 5.5 to 100 percent by study. Winters and his team categorized misdiagnoses based on four categories: vascular, which included conditions involving vessel blockages and bleeding, such as heart attack and stroke; all bacterial, viral and fungal infections; mechanical pathophysiological, a broad range of organ malfunction such as congestive heart failure and bowel obstruction; and cancer/other.

After collecting and classifying all error data, the researchers calculated how frequently misdiagnoses would be discovered if every patient who died in the ICU underwent an autopsy. Although autopsy is more frequently performed in complex patient cases in which the clinician may have a lower level of diagnostic certainty, the authors took this potential bias into account. Based on those adjustments, they say their calculations are conservative estimates.

Winters and his colleagues also found that, when compared with adult hospital patients overall, individuals in the ICU face up to a twofold risk of suffering a potentially fatal diagnostic mistake.

“It may be counterintuitive to think that the patients who are the most closely monitored and frequently tested are more commonly misdiagnosed, but the ICU is a very complex environment,” Winters says. Clinicians face a deluge of information in a distracting environment in which the sickest patients compete for attention, most without being able to communicate with their medical team. “We need to develop better cognitive tools that can take into account the 7,000 or more pieces of information that critical care physicians are bombarded with each day to ensure we’re not ruling out potential diagnoses,” Winters says.

Although two-thirds of discovered misdiagnoses did not directly contribute to the patient’s death, Winters says they’re an important indicator of accuracy and aren’t without costs. Patients may endure lengthened hospital stays, unnecessary surgical procedures and reduced quality of life because of non-fatal diagnostic mistakes, Winters adds.

The Armstrong Institute patient safety experts say the study points to the need for additional research to pinpoint the causes of misdiagnosis and identify tools to help diagnosticians more accurately assess patients.

###

This research was supported by a National Institute of Health training grant awarded to the Johns Hopkins University School of Medicine and a grant from the Agency for Healthcare Research and Quality (HS017755-01).

Other Johns Hopkins researchers who contributed to this study include Jason Custer, M.D.; Samuel M. Galvagno Jr., D.O., Ph.D.; Elizabeth Colantuoni, M.S., Ph.D.; Shruti G. Kapoor, M.D.; HeeWon Lee, B.A.; Victoria Goode, M.B.A., M.L.I.S.; Karen Robinson, M. Sc., Ph.D.; Atul Nakhasi, B.A.; and Peter Pronovost, M.D., Ph.D.

For more information:

http://www.hopkinsmedicine.org/neurology_neurosurgery/specialty_areas/neurocritical_care/profiles/team-member-profile/3CB2DB1281ED43D358A49F7F70A13575/Bradford_Winters

http://www.hopkinsmedicine.org/news/media/releases/diagnostic_errors_the_new_focus_of_patient_safety_experts

http://www.hopkinsmedicine.org/armstrong_institute/

An engineered mouse virus leaves us one step away from the ultimate bioweapon

Killer virus

An engineered mouse virus leaves us one step away from the ultimate bioweapon

A VIRUS that kills every one of its victims, by wiping out part of their immune system, has been accidentally created by an Australian research team. The virus, a modified mousepox, does not affect humans, but it is closely related to smallpox, raising fears that the technology could be used in biowarfare.

The discovery highlights a growing problem. How do you stop terrorists taking legitimate research and adapting it for their own nefarious purposes?

The Australian researchers had no intention of producing a killer virus. They were merely trying to make a mouse contraceptive vaccine for pest control. “But it’s a good way to show how to alter smallpox to make it more virulent,” says Ken Alibek, former second-in-command of the civilian branch of the Soviet germ-warfare programme.

Ron Jackson of CSIRO’s wildlife division and Ian Ramshaw at the Australian National University, both in Canberra, inserted into a mousepox virus a gene that creates large amounts of interleukin 4. IL-4 is a molecule that occurs naturally in the body. As part of a study aimed at creating a contraceptive vaccine, they were trying to stimulate antibodies against mouse eggs, which would make the animals infertile. The mousepox virus was merely a vehicle for transporting the egg proteins into mice to trigger an antibody response. The researchers added the gene for IL-4 to boost antibody production. The surprise was that it totally suppressed the “cell-mediated response”-the arm of the immune system that combats viral infection.

Mousepox normally causes only mild symptoms in the type of mice used in the study, but with the IL-4 gene added it wiped out all the animals in nine days. “It would be safe to assume that if some idiot did put human IL-4 into human smallpox they’d increase the lethality quite dramatically,” says Jackson. “Seeing the consequences of what happened in the mice, I wouldn’t be the one who’d want to do the experiment.”

To make matters worse, the engineered virus also appears unnaturally resistant to attempts to vaccinate the mice. A vaccine that would normally protect mouse strains that are susceptible to the virus only worked in half the mice exposed to the killer version. “It’s surprising how very, very bad the virus is,” says Ann Hill, a vaccine researcher from Oregon Health Sciences University in Portland. If bioterrorists created a human version of the virus, vaccination programmes would be of limited use.

Alibek, who now works on developing novel treatments for anthrax for the defence contractor Hadron in Virginia, says this highlights the drawback of working on vaccines against bioweapons rather than treatments. “I’d say any vaccine could be overcome by one or another genetically engineered virus or bacterium,” he says.

Is it possible that research into new vaccines against cancer and other diseases could inadvertently create lethal human viruses? Many of the most promising modern vaccines depend on viruses to transport genes into the body, and contain genes that directly alter the immune response. But researchers have not been too concerned because the evidence until now suggested that changes in the genetic make-up of viruses invariably makes them less virulent, not more. One way to reduce the risk, says Gary Nabel of the National Institutes of Health, is to use only viruses that cannot replicate. “There are some replication-competent [viral vaccines] around, but there is increasing concern about their use,” he says.

Defence experts are also worried about preserving the freedom to publish medical findings while trying to stop the information falling into the wrong hands. According to D. A. Henderson, a former US presidential adviser, and director of the Center for Civilian Biodefense Studies at Johns Hopkins University in Baltimore, what are effectively blueprints for making microorganisms more harmful regularly appear in unclassified journals. “I can’t for the life of me figure out how we are going to deal with this,” he says.

The Australian researchers consulted their country’s Department of Defence before submitting the work for publication, and only decided to go ahead after considerable thought. A report will appear in a February issue of the Journal of Virology. “We wanted to warn the general population that this potentially dangerous technology is available,” says Jackson. “We wanted to make it clear to the scientific community that they should be careful, that it is not too difficult to create severe organisms.”

###Author: Rachel Nowak, Melbourne

New Scientist issue: 13th January 2001

Please mention New Scientist as the source of this story and, if publishing online, please carry a hyperlink to: http://www.newscientist.com

Dangerous experiment in fetal engineering (MUST READ)

Public release date: 2-Aug-2012

Dangerous experiment in fetal engineering

Risky prenatal use of steroid to try to prevent intersex, tomboys and lesbians

CHICAGO — A new paper just published in the Journal of Bioethical Inquiry uses extensive Freedom of Information Act findings to detail an extremely troubling off-label medical intervention employed in the U.S. on pregnant women to intentionally engineer the development of their fetuses for sex normalization purposes.

The paper is authored by Alice Dreger, professor of clinical medical humanities and bioethics at Northwestern University Feinberg School of Medicine and is co-authored by Ellen Feder, associate professor of philosophy and religion at American University, and Anne Tamar-Mattis, executive director of Advocates for Informed Choice.

The pregnant women targeted are at risk for having a child born with the condition congenital adrenal hyperplasia (CAH), an endocrinological condition that can result in female fetuses being born with intersex or more male-typical genitals and brains. Women genetically identified as being at risk are given dexamethasone, a synthetic steroid, off-label starting as early as week five of the first trimester to try to “normalize” the development of those fetuses, which are female and CAH-affected. Because the drug must be administered before doctors can know if the fetus is female or CAH-affected, only one in eight of those exposed are the target type of fetus.

The off-label intervention does not prevent CAH; it aims only at sex normalization. Like Diethylstilbestrol (DES) — which is now known to have caused major fertility problems and fatal cancers among those exposed in utero — dexamethasone is a synthetic steroid. Dexamethasone is known — and in this case intended — to cross the placental barrier and change fetal development. Experts estimate the glucocorticoid dose reaching the fetus is 60 to 100 times what the body would normally experience.

The new report provides clear evidence that:

For more than 10 years, medical societies repeatedly but ultimately impotently expressed high alarm at use of this off-label intervention outside prospective clinical trials, because it is so high risk and because nearly 90 percent of those exposed cannot benefit.

Mothers offered the intervention have been told it “has been found safe for mother and child” but in fact there has never been any such scientific evidence.

The U.S. Food and Drug Administration has indicated it cannot stop advertising of this off-label use as “safe for mother and child” because the advertising is done by a clinician not affiliated with the drug maker.

A just-out report from Sweden in the Journal of Clinical Endocrinology and Metabolism documents a nearly 20 percent “serious adverse event” rate among the children exposed in utero.

Clinician proponents of the intervention have been interested in whether the intervention can reduce rates of tomboyism, lesbianism and bisexuality, characteristics they have termed “behavioral masculinization.”

The National Institutes of Health has funded research to see if these attempts to prevent “behavioral masculinization” with prenatal dexamethasone are “successful.”

The United States’ systems designed to prevent another tragedy like DES and thalidomide — involving de facto experimentation on pregnant women and their fetuses — appear to be broken and ineffectual.

###

The paper is available for free download at: http://www.springerlink.com/content/m1523l7615744552/?MUD=MP

Contact: Marla Paul
Marla-Paul@northwestern.edu
312-503-8928
Northwestern University