Can An Ugly Toenail Predict Amputation?

Nearly 3 in 4 people with diabetes at high risk for amputation have diseased toenails. These are the findings of a recent study presented at the Council of Nail Disorders in advance of the American Academy of Dermatology in Washington, DC. The study, coauthored by Drs. Stephanie Wu and David G. Armstrong of Scholl’s Center for Lower Extremity Ambulatory Research (CLEAR) at Rosalind Franklin University, was the first to rigidly evaluate a controlled group such as this.

“This study is something of a confirmation of what many have felt, but the ubiquity of the results is something of an eye-opener,” noted Dr. Wu. “It appears that if you have certain pre-existing risk factors for amputation coupled with a clinically diseased nail, chances are you have a significant fungal infection based on laboratory cultures. It is our hope that this study will assist us in making more rapid assessments and embark on much-needed therapy for these high-risk patients.”

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Rosalind Franklin University of Medicine and Science educates medical doctors, health professionals and biomedical scientists in a personalized atmosphere. The University is located at 3333 Green Bay Road, North Chicago, IL 60064, and encompasses Chicago Medical School, College of Health Professions, Dr. William M. Scholl College of Podiatric Medicine, and School of Graduate and Postdoctoral Studies. Visit at http://www.rosalindfranklin.edu/ and http://www.lifeindiscovery.com/. For more information about CLEAR, visit http://www.diabetic-foot.net/.

Contact: Kathy Peterson
Rosalind Franklin University of Medicine and Science

Researchers Discover Master Metabolism Regulator With Profound Effect On Fat Metabolism

Two biologists at Penn State have discovered a master regulator that controls metabolic responses to a deficiency of essential amino acids in the diet. They also discovered that this regulatory substance, an enzyme named GCN2 eIF2alpha kinase, has an unexpectedly profound impact on fat metabolism. “Some results of our experiments suggest interventions that might help treat obesity, prevent Type II diabetes and heart attacks, or ameliorate protein malnutrition,” said Douglas Cavener, professor and head of the Department of Biology, who led the research along with Feifan Guo, a research assistant professor. Their research appears in the scientific journal Cell Metabolism.

Organisms adapt metabolically to episodes of malnutrition and starvation by shutting down the synthesis of new proteins and fats and by using stores of these nutrients from muscle, fat, and the liver in order to continue vital functions. Cavener and Guo found that the removal of a single amino acid, leucine, from the diet is sufficient to provoke a starvation response that affects fat metabolism. “These findings are important for treating two major problems in the world,” Cavener says. “The starvation response we discovered can repress fat synthesis and induce the body to consume virtually all of its stored fat within a few weeks of leucine deprivation. Because this response causes a striking loss of fatty tissue, we may be able to formulate a powerful new treatment for obesity.”

The second problem is not excess food intake but insufficient protein intake, which plagues the populations of the poorer nations of Asia and Africa. The Food and Agriculture Organization of the United Nations estimates that 850 million people were malnourished between 1999 and 2005.[1] Those who eat a diet with sufficient calories that is lacking in an essential amino acid may suffer from stunted growth, developmental disorders, or even death. On the other hand, obesity is reaching near-epidemic proportions in wealthier nations. According to the Centers for Disease Control, 30 percent of U.S. adults over the age of 20 are obese.[2]

Rather than working with cells in culture, Guo and Cavener examined metabolic processes in a special strain of mice that lacks the GCN2 kinase and compared them with those of normal mice. “Organisms are remarkably sensitive to dietary intake,” Cavener says. “Being deprived of even one essential amino acid is enough for the GCN2 kinase to switch the metabolism into an emergency mode. Despite the fact that these mice are consuming normal amounts of carbohydrates and fats, they rapidly shut down fat synthesis in the liver and mobilize their stored fat deposits. Their bodies are literally tricked into a starvation mode.”

The experiments conducted by Guo and Cavener had striking and unexpected results. After 17 days of a leucine-deficient diet, the normal mice lost 48 percent of their liver mass and 97 percent of the adipose or fatty tissue from their abdomens. This response is very similar to what happens during starvation. In contrast, the mice without the GCN2 kinase kept a steady liver mass and lost only 69 percent of the adipose tissue on their abdomens.

One of the especially encouraging aspects of the research by Guo and Cavener was the short time frame in which dramatic changes could be induced. Even after only 7 days of leucine deprivation, the normal mice lost 50 percent of their fatty tissue. They also produced fewer lipids (fats) and showed a small drop in serum triglyceride levels. The mice lacking the GCN2 kinase did not lose as much fat as the normal mice did and, in addition, they developed very pale, fatty livers with unusually high levels of stored triglycerides because they continued to synthesize fatty acids. The remarkable rapidity of the weight change in the normal mice occurred because the repressed synthesis of new fats was coupled with the depletion of stored fats in the body.

These findings about the crucial regulatory role of GCN2 kinase in the metabolism have major implications for the treatment or prevention of obesity, which is associated with increased risk for heart disease, diabetes, hypertension, and osteoarthritis. “Most of all,” Cavener says, “we hope to be able to devise dietary interventions that will significantly improve the health of millions of children all over the world who suffer from amino acid deprivation associated with protein malnutrition.”

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MORE INFORMATION:

[1] Reference: Michael Wines, 2006. http://www.nytimes.com/2006/12/28/world/africa/28malnutrition.html “Malnutrition Is Cheating Its Survivors, and Africa’s Future” http://en.wikipedia.org/wiki/New_York_Times New York Times, December 28, 2006.

[2] Reference: http://www.cdc.gov/od/oc/media/pressrel/r991026.htm citing October 27, 1999 article published in JAMA, and http://www.cdc.gov/nccdphp/dnpa/obesity/.

Contact: Barbara K. Kennedy
Penn State

Alimera Sciences Receives FDA Approval To Market Alaway(TM) OTC For Up To 12 Hours Of Eye Itch Relief

Alimera Sciences Inc., an ophthalmic pharmaceutical company founded just three years ago, today announced that the U. S. Food and Drug Administration (FDA) has approved its ophthalmic solution Rx-to-OTC-switch new drug application (NDA) for Alaway(TM) (ketotifen fumarate ophthalmic solution 0.025%). Alaway(TM), a multiple action eye anti-allergic, is Alimera’s first NDA submission and the first to win approval. Indicated for the temporary relief of itchy eyes, Alaway(TM) will be marketed over-the- counter with the prescription strength active ingredient found in a prescription allergy eye drop.

An estimated 40 million people cope with itchy eyes associated with pollen, ragweed, grass, animal hair and dander — particularly during the spring and fall months. Unlike over-the-counter anti-itch eye drop products currently available, just one dose of Alaway(TM) offers eye itch relief within minutes and lasts up to 12 hours. Other over-the-counter products currently available offer no more than four hours of relief and require four doses per day. Alaway(TM), with its unique property of being both an antihistamine and a mast cell stabilizer addresses itchy eyes, the number one complaint among eye allergy sufferers.

“Developing Alaway(TM), submitting the application and achieving FDA approval for a three-year-old company is, indeed, an accomplishment of which Alimera is tremendously proud,” said Dan Myers, president and chief executive officer of Alimera Sciences. “The FDA’s approval of Alaway(TM) marks a milestone in Alimera’s overall strategy to consistently deliver innovative solutions to patient needs.

Alimera initially filed the NDA for Alaway(TM) in February of this year after completing a successful clinical study that showed it to be bioequivalent to Novartis’ Zaditor(R) (ketotifen fumarate ophthalmic solution 0.025%). Alaway(TM), in a 10mL bottle, is expected to be available to consumers in time to provide prescription strength relief for the spring 2007 allergy season.

About Alimera Sciences Inc.

Alimera Sciences Inc., a venture backed company, specializes in the development and commercialization of over-the-counter and prescription ophthalmology pharmaceuticals. Founded by an executive team with extensive development and revenue growth expertise, Alimera Sciences’ products address both the anterior (front) and posterior (back) segments of the eye. In August 2004, Alimera Sciences unveiled Soothe(R), the market’s first multi-dose, emollient-based artificial tear product, and in October 2005 initiated a Phase III clinical trial to study diabetic macular edema (DME) patients treated using Medidur(TM) with fluocinolone acetonide, the company’s pharmacologic treatment for DME.

Alimera Sciences Inc.
http://www.alimerasciences.com

City Kids With Asthma Lose Out On Preventive Treatment

A new study by specialists at the Johns Hopkins Children’s Center and elsewhere suggests that only one in five inner-city children with chronic asthma gets enough medicine to control dangerous flare-ups of the disease.

The findings, reported in December’s Pediatrics, are disturbing, the researchers say, because preventive therapy failure leads to over-reliance on fast-acting ‘rescue’ drugs after an asthma attack strikes and to more complications and increased risk of death.

The scientists interviewed parents of 180 Baltimore city children 2 to 9 years of age diagnosed with persistent asthma and studied pharmacy records. Overall, only 20 percent of the 180 got the recommended amount of daily controller medication, which is six or more refills in a 12-month period. Sixty percent of children got too little therapy to fully prevent flare-ups and 20 percent either got no medication at all or relied solely on quick-relief rescue drugs, which stop an asthma attack from progressing.

Current guidelines call for any child asthmatic with wheezing, coughing and shortness of breath two or more times a week or night-time symptoms two or more times a month to use inhaled corticosteroids as controller drugs to curb inflammation and prevent acute attacks.

“It’s clear that kids who need preventive drugs aren’t getting them,” says lead author Arlene Butz, Sc.D., R.N., asthma specialist at the Children’s Center. Previous research indicates that inner-city children are at special risk because their living conditions include other asthma triggers, such as exposure to secondhand smoke and mouse and cockroach allergens.

The survey also showed that children cared for by asthma specialists in or out of the hospital were more likely to follow a proper drug regimen than those who were not in these groups.

Butz and colleagues said training primary care pediatricians to check pharmacy records will help them monitor their patients’ adherence to the prescribed drug regimen.

Asthma is the country’s leading pediatric chronic illness, affecting 6.2 million children under the age of 18.

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Other Hopkins researchers in the study: Kim Mudd, M.S.N., of the Children’s Center; and Michele Donithan, M.H.S., of the Johns Hopkins Bloomberg School of Public Health.

Other institutions participating in the study: University of Maryland. The study was funded by the National Institute of Nursing Research.

Contact: Katerina Pesheva
Johns Hopkins Medical Institutions

Biosensors At The Bedside: New Testing Device Could Revolutionize Health Care

In hospitals today, the first warning that a post-operative patient is going into septic shock is often when the patient’s blood pressure collapses and congestive heart failure begins. By that time the patient has a high probability of dying, or if he survives, an even higher probability of permanent major organ damage after a long stay in an intensive care unit.

A new company, SpheroSense Technologies Inc., will produce a hand-held device that will monitor post-operative and trauma patients for early warning signs of sepsis, or infection in the bloodstream, so medical personnel can intervene with antibiotics and anti-inflammatories before organs are damaged. This would reduce the likelihood of death or disability and prevent many expensive stays in ICUs.

The company was founded a year ago by Professor James A. Glazier and two colleagues, Professor Bogdan Dragnea and doctoral student Dragos Amarie, in the Biocomplexity Institute at Indiana University Bloomington. Dr. James Kuo has joined the firm as Interim CEO and Andrew Cothrel as Interim COO.

Bacteria often circulate at low levels in the bloodstream prior to the onset of sepsis. SpheroSense will detect them by continuously tracking the concentration of specific protein markers in patients’ bloodstreams. Such continuous monitoring cannot be performed by any current or announced device, Glazier said.

“The incidence of sepsis exceeds that of colon cancer, breast cancer or AIDS. There are about a million cases of sepsis every year in the United States, and the mortality rate is more than 30 percent,” he said.

No hospital would check patients’ pulses only once a day to see if they were alive, yet patients are lucky if their blood chemistry is checked even that often. The tests are expensive, and despite the growing market for bedside (point-of-care) testing, the tests are usually done in a central or remote laboratory.

“In 10 years, we will regard continuous monitoring of blood chemistry as routine and essential, and such monitoring will improve therapy and save lives and money,” Glazier said. Rapid testing at the patient’s bedside has the potential to revolutionize the delivery of health care.

Glazier and his colleagues have developed a new type of miniature optical device, the microcavity surface plasmon resonance sensor, which is able to detect and quantify molecular binding in very small volumes of a sample. This sensor improves on the performance of the hundred-thousand-dollar instruments currently used in drug-discovery and biochemistry laboratories worldwide, including at IU and at Eli Lilly and Co., while greatly reducing the cost per measurement. This will allow very low-cost, continuous screening for medical applications as well as high-throughput instruments for research and drug discovery.

“The company’s goal is to become the leader in continuous-monitoring, molecular interaction devices for research, medical and safety applications,” Glazier said. “We believe that a significant market exists for a low-cost, flexible and high-performance instrument.”

Potential customers include leading life science research centers, all of the leading global pharmaceutical companies, and a large number of companies in the biotechnology sector. “We believe that a compact, low-cost instrument with high-throughput capabilities would find its way into almost every current biochemistry laboratory,” Glazier said.

“Our sensor is significantly smaller and more sensitive than existing related technologies,” he said. “Unlike most existing technologies, the MSPR sensor can detect small molecules, drugs, proteins, viruses, DNA and RNA. The sensor can be manufactured inexpensively enough to be disposable, and it can be integrated with microfluidics into instruments that allow sample conditioning and high-throughput screening of multiple compounds or pathogens on the same chip. Our technology will provide continuous real-time monitoring of patient condition.”

The main impact will be in medical diagnostics, he emphasized.

SpheroSense was started with seed money from Indiana University. The company is now requesting $1.75 million from the state’s 21st Century Fund to develop prototypes and begin production.

Glazier said the helpful environment at IUB, in Bloomington and in the state of Indiana has been crucial in convincing them to take the plunge into a commercial venture. “The level of support available here is outstanding. When we started, none of us had any experience in turning scientific concepts into a viable business. People at all levels have been exceptionally generous with their time and advice, and very patient with our mistakes.

“Getting a hearing would have been much more difficult in Boston or San Diego,” Glazier noted. “The people at Indiana University Research and Technology Corp., particularly Bill Brizzard and Mark Long, have been crucial in helping us develop our concepts into commercial applications and a company. John Cameron, a former physics professor at IUB who founded ProCure, was a great mentor. A group of students from the Johnson Center for Entrepreneurship & Innovation in IU’s Kelley School of Business is currently helping to develop our marketing plan. Without the valuable assistance of Professor Donald Kuratko and the Johnson Center, we would have had a much more difficult time organizing our business plan. We’ve also benefitted from advice and opportunities to meet with successful entrepreneurs and venture capitalists provided by Ted Widlanski (MetaCyt) at IU, Steve Bryant (formerly with Bloomington Life Sciences Partnership) and Brian Kleber (inVenture) in Bloomington, and Cynthia Helpingstine (BioCrossroads) at the state level.”

The initial focus will be on developing a laboratory research instrument. “Because this application does not require approval by the Food and Drug Administration, we could enter the market quickly. Subsequently, we will develop products for the clinical point-of-care market using the same technologies,” Glazier said.

In the clinical market, the initial focus will be on patients in intensive care units who, because of a large number of intravenous lines, tubes and catheters, are at high risk for bloodstream infection. The clinical setting is ideal for using MSPR technology because of the need for a hand-held device, a highly sensitive and specific test, and a rapid turn-around time on the test in a life-threatening situation.

Proof of concept has already been demonstrated, showing the remarkable sensitivity of MSPR. This technology is the basis for a patent application by Indiana University Research and Technology Corp., and SpheroSense has negotiated exclusive rights on this technology and expects to extend it through further innovation. Additional applications could include drugs of abuse, influenza screening, biodefense and suspicious “white powder” detectors, among others.

Indiana University
530 East Kirkwood Ave., Ste 203
Bloomington, IN 47408-4003
United States
http://www.indiana.edu/

Countries Should Find Balance Between Affordable Drugs, Development Incentives, WHO Director-General Says In Letter To Thai Health Minister

World Health Organization Director-General Margaret Chan in a letter to Thai Health Minister Mongkol na Songkhla said that although the Thai government was fully within its rights to issue a compulsory license for Abbott Laboratories antiretroviral drug Kaletra, countries should find the “right balance” between providing affordable medicines and incentives for drug companies to develop new treatments, Reuters reports (Reuters, 1/13). Mongkol last month signed the compulsory license, which allows Thailand to produce a lower-cost version of Kaletra, into law. World Trade Organization regulations allow governments to declare a “national emergency” and issue compulsory licenses without consulting the foreign patent owner. Thailand, which has 580,000 people living with HIV/AIDS, has won international recognition for its quick launch of a national drug program that treats more than 82,000 HIV-positive people. However, the government’s commitment to providing universal access to care is facing increasingly high drug costs. The compulsory license could save the country as much as $24 million annually. According to a joint statement released earlier this month by the health ministry and Abbott, the two sides agreed in principle to reduce the price of Kaletra in Thailand to increase access to the drug among HIV-positive people who have developed resistance to other antiretrovirals. The lower price will apply only to Thailand’s public health programs and will not apply to private hospitals, people with high incomes or foreign patients. Abbott offered to lower Kaletra’s cost to $167 per patient monthly, although representatives from the health ministry said that was still too high. Abbott and the ministry agreed to meet for further negotiations in one month (Kaiser Daily HIV/AIDS Report, 2/9).

Chan’s Letter, Reaction
In the letter, Chan said the Thai government was fully within its rights under WTO regulations to issue compulsory licenses. However, she added that she “firmly believe[s] that the pharmaceutical industry — generic manufacturers and research and development companies — are part of the solution.” Countries are not required to negotiate with patent holders before issuing a license, but “prior negotiations with industry is a pragmatic approach that may ensure countries have access to high quality medicines and at affordable prices,” Chan said. According to Reuters, Chan’s letter in part was a response to some HIV/AIDS advocates who have criticized her for not supporting Thailand’s decision during her visit to the country two weeks ago. “We expected that [Chan] would have congratulated Thailand for its efforts … to increase public health and access to medicines for its people,” a coalition of more than 400 AIDS advocates and groups wrote in a letter to Chan last week (Reuters, 2/13). In addition, Mongkol on Monday said that a Ministry of Health panel is examining drugs, including HIV/AIDS medications, that the country needs and could make or buy generic versions of while completing negotiations with pharmaceutical companies. He added that if the pharmaceutical companies reduce the cost of their drugs to a level the country is “satisfied” with, Thailand will not enforce the compulsory license. “We don’t call this a threat but a negotiation for the country’s benefit,” he said (Wong-Anan, Reuters, 2/12). Thailand’s Pharmaceutical Research and Manufacturers’ Association on Thursday said it believes the government is planning to issue compulsory licenses for an additional 11 drugs, including antiretrovirals. The decision to issue compulsory licenses is “major and regrettable,” the association said in a statement, adding that the health ministry’s “actions risks limiting development of next-generation treatments and could lead to the proliferation of low-quality medicines.” A senior health ministry official would not confirm if the government is planning to issue the licenses for the additional drugs (AFP/Nation, 2/15).

“Reprinted with permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

A Rapid New Process For Fabricating Microstructures From Protein

In an advance in microfabrication technology, scientists report development of a new method for rapidly engineering complex micro-scale patterns and three-dimensional microstructures from biocompatible protein.

Jason B. Shear and Bryan Kaehr describe using the laser technique to fabricate detailed shapes – such as the silhouette of a housefly and the State of Texas – by condensing (or crosslinking) proteins in solution into a solid matrix. Their study is scheduled for the Feb. 28 issue of the Journal of the American Chemical Society, a weekly publication. The researchers also used the process to fabricate minute 3-D structures, including 1- and 2-story microcontainers that were used to trap, incubate and grow as few as a single living bacterium into colonies. Such traps could have a variety of uses, including studying the formation of biofilms, which are the source of human health concerns.

The technique, mask-directed multiphoton lithography, is modeled after the photolithography processes widely used to transfer electronic circuits onto a semiconductor wafer by projecting light through a pattern or “mask.” However, the new method uses a special laser to scan objects or patterns printed on transparency film with an ordinary desktop printer. The silhouette ultimately is refocused into the protein solution using the objective lens of a microscope. Because protein molecules must be extremely close to the laser focus to undergo crosslinking into solid material, this method allows structures to be created with complex 3-D shapes. The process takes only minutes, researchers report.

CONTACT:
Jason B. Shear, Ph.D.
University of Texas
Austin, Texas 78712

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ACS News Service weekly PressPac

The American Chemical Society – the world’s largest scientific society – is a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.

Contact: Michael Woods
American Chemical Society

Faith-Based Organizations Major Contributors To Fight Against HIV/AIDS In Sub-Saharan Africa, Report Says

Faith-based organizations are playing a major role in the fight against HIV/AIDS in sub-Saharan Africa, according to a World Health Organization report released this week, IRIN/AllAfrica.com reports. According to the report — titled “Appreciating Assets: Mapping, Understanding, Translating and Engaging Religious Health Assets in Zambia and Lesotho” — Christian hospitals and health centers provide about 40% of HIV/AIDS medical care in Lesotho and manage nearly one-third of treatment facilities in Zambia. The report found that faith-based organizations seldom are credited for their efforts to increase access to antiretroviral treatment and provide care to those living with HIV/AIDS on the continent, IRIN/AllAfrica.com reports. According to WHO, faith-based organizations make up 30% to 70% of the health infrastructure in sub-Saharan Africa. Patrick Purtill, director of new partner outreach in the Office of the U.S. Global AIDS Coordinator, said failing to recognize that faith-based organizations “possess an extensive geographic reach and a well-developed infrastructure in the developing world” could hinder efforts to fight HIV/AIDS. Francois Venter, director of the Southern African HIV Clinicians Society, said that churches and faith-based organizations are “uniquely positioned to help realize the goal of universal access to HIV prevention, treatment, care and support in Africa as a result of their stature in the communities.” Ted Karpf, partnerships officer in WHO’s HIV/AIDS Department, in a statement said, “This data demands that we continue to explore and expand the field,” adding that the report is the “first serious study of FBO engagement in HIV/AIDS, but it cannot be the last” (IRIN/AllAfrica.com, 2/13).

The report is available online.

“Reprinted with permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Exercise Pivotal In Preventing And Fighting Type II Diabetes

One in three American children born in 2000 will develop type II diabetes, according to the U.S. Centers for Disease Control and Prevention (CDC). A new study at the University of Missouri-Columbia says that acute exercise — as little as 15 minutes a day — can have a profound influence on preventing and fighting the disease.

This research adds to the body of evidence that indicates exercise can fight type II diabetes, one of the most widespread self-inflicted healthcare struggles in the United States, and could save Americans millions of dollars in pills, injections and medical treatment. Acute exercise is a bout of activity in which people actively participate, as opposed to activity resulting from everyday activities.

“Many people can fight type II diabetes through diet and exercise alone,” said John Thyfault, professor in the MU College of Human Environmental Sciences’ Department of Nutritional Sciences. “It is important to ward off diabetes early. Exercise has proven to be effective at all levels. At any stage of type II diabetes, from an obese child to a person dependent for 20 years on insulin injections, exercise could have a dramatic effect on improving insulin sensitivity.”

Type II diabetes results from a lack of insulin production and insulin resistance in skeletal muscle cells. Insulin is necessary to help drive glucose out of the blood and into the tissues of the body. As a result of insulin resistance, cells do not respond appropriately to insulin, causing more insulin to be released to have a measurable effect and ultimately causing insulin and glucose to build up dangerously in the blood.

Thyfault’s study found that relatively short periods of acute muscle exercise in diabetic Zucker rats significantly increased insulin sensitivity in the previously insulin resistance skeletal muscles. Since 80 to 90 percent of all glucose goes into muscle after a meal, it is reasonable that more active muscles on a day- to-day basis will result in increased insulin sensitivity, Thyfault said.

“In relation to a person with type II diabetes, this would mean that they could lessen their dependence on insulin therapy to control their blood glucose levels or potentially control glucose levels without any drug by just increasing their daily activity levels in addition to the right diet,” Thyfault said.

The study, “Contraction of insulin resistant muscle normalizes insulin action in association with increased mitochondrial activity and fatty acid catabolism,” will be published in the American Journal of Physiology-Cell.

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Contact: Jennifer Faddis
University of Missouri-Columbia

Articles In The New England Journal Of Medicine Confirm On-Label, Long-Term Safety And Efficacy Of The CYPHER(R) Sirolimus-Eluting Coronary Stent

The long-term safety of the CYPHER(R) Sirolimus-eluting Coronary Stent, specifically in terms of death, myocardial infarction (heart attacks) and stent thrombosis (also known as blood clots), is comparable to that of bare metal stents when used according to product labeling, according to a variety of studies appearing today in the New England Journal of Medicine (NEJM). These studies also confirm the long- term efficacy of the CYPHER(R) Stent in substantially reducing the need for another interventional procedure (revascularization) compared to bare metal stents.

“We are extremely pleased that long-term data from multiple on-label randomized, controlled clinical studies comparing the CYPHER(R) Stent with bare metal stents are now published in a peer reviewed journal,” said David Kandzari, M.D., F.A.C.C., F.S.C.A.I, Chief Medical Officer, Cordis Cardiology division of Cordis Corporation. “These studies reaffirm the long-term safety and efficacy of this important treatment option for coronary artery disease. This should give more confidence to interventional cardiologists and their patients.”

Clinical data covered by NEJM were presented previously at the U.S. Food and Drug Administration advisory panel hearing in December 2006 on the safety of drug-eluting stents.

Dr. Kandzari noted that the current CYPHER(R) Stent database, which includes more than 45,000 patients, represents the broadest clinical data set of any drug-eluting stent and that studies evaluating the CYPHER(R) Stent in higher risk patients not currently within the approval labeling, including those with diabetes and lesion subgroups, will continue to be a focus of ongoing clinical research at Cordis.

“We are committed to continuously building on the growing body of clinical knowledge about the CYPHER(R) Stent and its use in a variety of patients and lesion types so interventional cardiologists and their patients can discuss all treatment options for coronary artery disease,” said Dr. Kandzari. “The goal of our clinical research program is to examine early and late efficacy and safety outcomes, including the safety and efficacy of anti-platelet therapy and its relationship to stent thrombosis. Through ongoing randomized controlled clinical trials we can understand better the safety and efficacy of the CYPHER(R) Stent when used in complex patients not originally included in early clinical trials, which is often referred to as ‘off-label’ use.”

Cordis conducts both randomized clinical trials as well as ‘real world’ registries to continuously gather data about the use of the CYPHER(R) Stent. “While data from registries, like that from Sweden in this edition of the Journal, are helpful in providing insights into off-label use, they are not definitive and need to be confirmed with randomized, controlled clinical trials, which are the highest level of clinical evidence in medicine,” Dr. Kandzari said.

Pooled Analysis of 14 Randomized Clinical Trials

NEJM includes a report of a pooled analysis of patient-level data out to five years from 14 randomized controlled trials comparing the CYPHER(R) Stent to bare metal stents in more than 4,900 patients. This is the most comprehensive study conducted to date; it provides the most in depth information about the safety and efficacy of the product.

It encompasses randomized controlled studies of on-label use, as well as dedicated studies of broader patient populations not within the approved labeling. Currently, off-label use would include those with diabetes, in- stent restenosis, chronic total occlusions, acute myocardial infarction and unselected patient populations.

In this meta-analysis, there was no significant difference in the overall risk of stent thrombosis between the CYPHER(R) Stent and bare metal stents over four years (p=0.16) although there was an increase in risk of stent thrombosis with the CYPHER(R) Stent after one year. However, if patients who had intervening repeat revascularizations are included in the analysis, as they are when applying definitions of stent thrombosis developed by the Academic Research Consortium, there were eight late thromboses in patients treated with the CYPHER(R) Stent and six in those treated with bare metal stents.

In addition, the overall risk of death and the combined risk of death and myocardial infarction (heart attack) were not significantly different between the two treatment arms (p=0.76) in the meta analysis. Of note, there was also a significant reduction in the combined risk of death, myocardial infarction or reintervention with the CYPHER(R) Stent compared to bare metal stents (p
People with Diabetes Treated with the CYPHER(R) Stent

People with diabetes are known to be at increased risk of coronary complications. However, in this pooled analysis, the use of the CYPHER(R) Stent in patients with diabetes was not associated with a higher risk of death or the combined endpoint of death or myocardial infarction. Data from earlier clinical trials and registries of the safety and efficacy of drug-eluting stents in patients with diabetes were inconsistent. The use of the CYPHER(R) Stent and other drug-eluting stents in patients with diabetes is not presently within approved labeling for these devices.

Dr. Kandzari noted that the total body of clinical evidence, particularly with randomized clinical trials, does not suggest there is an excess mortality with the CYPHER(R) Stent in either the total population or in patients with diabetes.

“We share the concern of physicians and patients about the risk of late stent thrombosis and are expanding our long-term clinical trials (SIRIUS, e- SIRIUS and c-SIRIUS) out to eight years to continue gathering clinical information,” said Dr. Kandzari. “We know late stent thrombosis may be related to various factors including the discontinuation of dual anti-platelet therapy. While the medical community endeavors to better understand the optimal length of therapy for anti-platelet therapy, we support guidelines recently announced by key medical and patient societies, namely the American Heart Association, the American College of Cardiology and the Society for Interventions and Angiography, that recommend up to 12 months of anti-platelet therapy for patients who can tolerate it.”

About the CYPHER(R) Stent

The CYPHER(R) Stent has been chosen by cardiologists worldwide to treat approximately three million patients with coronary artery disease. The safety and efficacy of the device is supported by a robust clinical trial program that includes more than 70 studies, including a number of independent clinical trials, that examine the performance of the CYPHER(R) Stent in a broad range of patients.

Developed and manufactured by Cordis Corporation, the CYPHER(R) Stent is currently available in more than 80 countries and has the broadest clinical experience and longest-term clinical follow-up of any drug-eluting stent. The next version of sirolimus-eluting stent, the CYPHER(R) SELECT(TM) Sirolimus- eluting Coronary Stent, was launched in Europe, Asia Pacific, Latin America and Canada in 2003. CYPHER(R) SELECT(TM) Plus, the third version of a sirolimus-eluting coronary stent, received CE Mark in 2006 and is currently available in many markets outside the U.S.

For more complete information on indications, contraindications, warnings and precautions, see the Instructions for Use available at http://www.cypherstent.com.

About Cordis Corporation

Cordis Corporation, a Johnson & Johnson company, is a worldwide leader in the development and manufacture of interventional vascular technology. Through the company’s innovation, research and development, Cordis partners with interventional cardiologists worldwide to treat millions of patients who suffer from vascular disease. More information about Cordis Corporation can be found at http://www.cordis.com.

Cordis Corporation has entered into an exclusive worldwide license with Wyeth for the localized delivery of sirolimus in certain fields of use, including delivery via vascular stenting. Sirolimus, the active drug released for the stent, is marketed by Wyeth Pharmaceuticals, a division of Wyeth, under the name Rapamune(R). Rapamune is a trademark of Wyeth Pharmaceuticals.

Cordis Corporation
http://www.cordis.com