Friday, September 2, 2011

TGI Friday HCV News:Adherence to Treatment for Hepatitis C

Name: Morning News Artist Jack Vettriano

New On The Blog

Hepatitis C in Minority Populations
Trial Supports Addition of Telaprevir for HCV Genotype 2
Early TIPS for Ascites Study Seeks to Improve Survival

New On The Web Site
Study Suggests HCC Resection Superior to Transplant
Hepatitis C; Type II Cryoglobulinemia
Two New Videos; Posted in Multimedia

Todays News

From HIV and Hepatitis

What Factors Influence Adherence to Treatment for Hepatitis C?
Efficacy, or likelihood of achieving sustained virological response, was the most important factor influencing adherence among people considering treatment for chronic hepatitis C, according to a recent survey.
Increasing rates of non-adherence over time suggest that achieving SVR may not be the only important treatment factor taken into account by people with HCV. Skipping doses may indicate that patients are willing to reduce the likelihood of achieving sustained response in order to avoid treatment side effects.

September 2011 HCV Advocate Newsletter

In This Issue:
NYC: Sexual Transmission of HCV Among HIV Positive Men
Alan Franciscus, Editor-in-Chief
Important Updates at the HCV Advocate HealthWise: Back at Hepatitis C
Lucinda K. Porter, RN
Disability & Benefits: Medicare—Getting the Most Out of It
Jacques Chamber, CLU
HCV Snapshots
Lucinda K. Porter, RN
Clinical Trials
Alan Franciscus, Editor-in-Chief

Dendritic Cells in Liver Protect Against Acetaminophen Toxicity
Released: 9/1/2011 4:10 PM EDT
Source: New York University Langone Medical Center
Newswise —
NYU School of Medicine researchers have discovered that dendritic cells in the liver have a protective role against the toxicity of acetaminophen, the widely used over-the-counter pain reliever and fever reducer for adults and children. The study’s findings are published in the September issue of the journal Hepatology.

The liver is the organ that plays a central role in transforming and filtering chemicals from the body. High-doses of acetaminophen can cause hepatotoxicity, chemical driven liver damage. In fact, accidental and intentional acetaminophen overdose are the most frequent causes of acute liver failure (ALF) in the United States. Acetaminophen related liver failure by intentional or accidental overdose causes 56,000 emergency room visits, 2,600 hospital visits and 450 deaths annually. As a result, this year the FDA mandated drug manufacturers to start limiting the amount of acetaminophen in combination drug products and is currently exploring adding safer dosing instructions to children’s acetaminophen products.

In the new study, researchers found an abundance of dendritic cells in the liver can protect the organ from acetaminophen damage while low levels of dendritic cells in the liver are associated with exacerbated liver damage, liver cell and tissue death, known as centrilobular hepatic necrosis, and acute liver failure from acetaminophen.

“Our research results confirm a central role for dendritic cells and their powerful regulation of acetaminophen’s toxicity,” said George Miller, MD, senior author of study and assistant professor, Departments of Surgery and Cell Biology at NYU Langone Medical Center. “High levels of dendritic cells have a novel, critical and innate protective role in acetaminophen hepatotoxicity. We now have greater insight into the liver’s tolerance of acetaminophen toxicity and dendritic cell regulation of these toxins.”

In the study, researchers used acetaminophen-induced hepatic injured mice models to closely examine the protective role of dendritic cells. Dendritic cells are the main antigens in the liver that trigger an immune response and control the liver’s tolerance to high doses of invading toxins like acetaminophen. In the experiment all mice were injected with acetaminophen but some mice models were first depleted of dendritic liver cells using a diphtheria toxin while others had their dendritic cell levels bolstered with Flt3L, a protein in the blood previously shown to increase proliferation of dendritic cell levels.

Researchers discovered dendritic cell depletion exacerbates acetaminophen’s damage to the liver. The acetaminophen treated mice with depleted dendritic cells had more extensive liver cell and tissue death compared to other mice. Also, these mice died within 48 hours of acetaminophen challenge- whereas death was rare in other mice without dendritic cell depletion. In addition, the study shows dendritic cell expansion successfully diminished the hepatotoxic effects of acetaminophen protecting the liver from damage.

“Understanding the regulatory role of dendritic cells is an important step in the development of immune-therapy for acetaminophen induced liver injury,” said Dr. Miller, a member of the NYU Cancer Institute. “Advanced studies are warranted to investigate further the protective role of dendritic cells in humans and their use as a possible new therapeutic target for liver failure prevention in the future.”

About NYU Langone Medical Center

NYU Langone Medical Center, a world-class, patient-centered, integrated, academic medical center, is one on the nation’s premier centers for excellence in clinical care, biomedical research and medical education. Located in the heart of Manhattan, NYU Langone is composed of three hospitals – Tisch Hospital, its flagship acute care facility; the Rusk Institute of Rehabilitation Medicine, the world’s first university-affiliated facility devoted entirely to rehabilitation medicine; and the Hospital for Joint Diseases, one of only five hospitals in the nation dedicated to orthopaedics and rheumatology – plus the NYU School of Medicine, which since 1841 has trained thousands of physicians and scientists who have helped to shape the course of medical history. The medical center’s tri-fold mission to serve, teach and discover is achieved 365 days a year through the seamless integration of a culture devoted to excellence in patient care, education and research.
For more information, go to

Stem Cells

From Nature

Q&A with the new head of the NIH stem cell center
In October 2005, Mahendra Rao shocked the scientific community when he quit his job as head of the US National Institute on Aging’s stem-cell section and announced plans to go into industry.

The $52-million, seven-year center was launched in early 2010 by the agency to develop new therapies using stem cell approaches. With a heightened focus at the NIH on translational medicine, Elie Dolgin spoke to Rao to find out how he plans to turn stem cell discoveries into cell-based therapies.

What sets the regenerative medicine center apart from other academic institutes dedicated to stem cell technologies?

Neither in size nor in scientific quality could one say that this center is any different from some of the other more established centers. However, there are two crucial differences. One, this is a government center, and the government’s mandate is different than that at any other center. So, that’s a really important distinction. The second thing is that the center doesn’t function in isolation. It’s what’s around it that makes it very useful, and what’s around it is a whole lot of infrastructure and investment that’s gone in to building up a way to take things from the bench to the bedside. There are two really important pieces to that in the NIH Chemical Genomics Center and the NIH Clinical Center. Both of them are widely recognized, state of the art, best in class type of centers...... Continue Reading...



Expert Rev Gastroenterol Hepatol. 2011 Aug;5(4):503-16.
Current understanding of insulin resistance in hepatitis C.
Kaddai V, Negro F.
Department of Pathology and Immunology, Centre Médical Universitaire, Rue Michel-Servet 1, 1205 Geneva, Switzerland.

Important breakthroughs have been made in recent years into understanding the close interaction between hepatitis C virus (HCV) infection and glucose homeostasis. Both cross-sectional and longitudinal studies have demonstrated that infection with HCV is associated with an increased risk of developing insulin resistance and Type 2 diabetes. A direct effect of HCV on hepatocyte insulin signaling has been shown in experimental models. Some preliminary observations seem to suggest that indirect mechanisms involving extrahepatic organs might also play a role. The interaction between HCV and glucose metabolism has significant clinical consequences.

Insulin resistance and Type 2 diabetes not only accelerate the histological and clinical progression of chronic hepatitis C, but also reduce the virological response to IFN-α-based therapy. Thus, understanding the mechanisms underlying HCV-associated glucose metabolism derangements is of paramount interest in order to improve the clinical management of chronic hepatitis C. This article will focus on the studies that consistently argue in favor of an interrelation between HCV and insulin resistance and will highlight the latest discoveries in this field.

Related-Diabetes Updates On The Blog
ScienceDaily (Sep. 1, 2011) —
Robert Winkler says he limped around on his painful left foot for six months, suffering unnecessarily from a misdiagnosis by a physician who didn't know about the symptoms and treatments for Charcot foot, a form of localized osteoporosis linked to diabetes that causes the bones to soften and break, often resulting in amputation.

When his primary care physician finally agreed to Mr. Winkler's request for an x-ray, they discovered the metatarsal bones in Mr. Winkler's left foot were all broken -- a common symptom of this serious and potentially limb-threatening lower-extremity complication.
A new article in the September issue of the journal, Diabetes Care, describes Charcot foot and its treatment with a goal of educating medical professionals about this painful inflammation of the foot. The article is the product of an international task force of experts convened by the American Diabetes Association and the American Podiatric Medical Association in January to summarize available evidence on the pathophysiology, natural history, presentations and treatment recommendations for Charcot foot syndrome.

"Even though it was first described in 1883, the diagnosis and successful treatment of Charcot foot continue to be a challenge because this syndrome is not widely known or understood by the broader medical profession," said Lee C. Rogers, D.P.M., co-director of the Amputation Prevent Center at Valley Presbyterian Hospital in Van Nuys, CA, and lead author of the Diabetes Care article. "Charcot foot is now considered to be an inflammatory syndrome most often seen in patients with diabetes which can be successfully treated in its early stages."
The article describes Charcot foot as a condition affecting the bones, joints and soft tissues of the foot and ankle, which is characterized by inflammation in the earliest phase and is associated with diabetes and neuropathy. The report finds offloading, or removing weight from the foot, is the most important initial treatment recommendation. Surgery can be helpful in early stages involving acute fractures of the foot or ankle or in later stages when offloading is ineffective, according to the article.

In Mr. Winkler's case, he was first diagnosed with Charcot foot in 2004 and had already undergone one surgery that relieved the problem for several years. By 2010, though, he was facing the potential amputation of the foot because of complications associated with Charcot foot syndrome.

His podiatrist referred him to Dr. Rogers at Valley Presbyterian Hospital's Amputation Prevention Center, an integrated limb salvage center that is one of only a handful in the nation. Since its December 2009 opening, the Amputation Prevention Center's specialized multidisciplinary team of highly skilled professionals has treated patients from all over the country and around the world with leading-edge technology, achieving a limb salvage rate of 96 percent.

George Andros, M.D., the Center's Medical Director, performed vascular surgery to restore circulation to Mr. Winkler's left foot so that it would heal. Then, Dr. Rogers performed surgery to rebuild the bones in Mr. Winkler's foot. Dr. Rogers also implanted a bone stimulator that acts like a pacemaker for bones which encourages Mr. Winkler's body to rebuild and fuse the broken bones in his left foot. As a result, Mr. Winkler is expected to be able to recover the use of his left foot.

"I'm very pleased because I had gone to another doctor and he wanted to amputate my foot," Mr. Winkler said. "When I found Dr. Rogers and Valley Presbyterian Hospital's Amputation Prevention Center, it's like I found a blessing and an angel in disguise. I have tears running down my face as I describe to you how I will be able to get up out of my chair and walk because of the care I received at Valley Presbyterian Hospital. All the people there are superb. They treat me like a king."

Story Source:
The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Valley Presbyterian Hospital, via EurekAlert!, a service of AAAS.

Journal Reference:
L. C. Rogers, R. G. Frykberg, D. G. Armstrong, A. J. M. Boulton, M. Edmonds, G. H. Van, A. Hartemann, F. Game, W. Jeffcoate, A. Jirkovska, E. Jude, S. Morbach, W. B. Morrison, M. Pinzur, D. Pitocco, L. Sanders, D. K. Wukich, L. Uccioli. The Charcot Foot in Diabetes. Diabetes Care, 2011; 34 (9): 2123 DOI: 10.2337/dc11-0844


Learn More From Medical News Today;
What Is Sjogren's Syndrome? What Causes Sjogren's Syndrome?
Primary Sjogren's syndrome - experts are not sure what the exact cause of Sjogren's syndrome is. Most believe it is likely to be a combination of environmental and genetic factors. Some people are probably born with certain genes that make them more susceptible to having an abnormal immune system. Sometime during their life, an environmental factor, such as hepatitis C viral infection, or an infection with the Epstein-Barr virus may have triggered the immune system not to work properly.

Challenges in understanding Sjögren's syndrome - improved insights into the pathogenesis generate hope for innovative therapies?
Published:19 August 2011
With this in mind, the authors of these reviews address central questions about the immunopathogenesis of Sjögren syndrome. Sipsas and colleagues [4] explore the potential role of retroviruses in initiating or maintaining disease. Vitali [5] examines the differences and similarities of sicca symptoms and risk of developing lymphoma between patients with HIV or hepatitis C virus infection and those with Sjögren syndrome

From Medpage

Sjogren's Sidelines Venus Williams
By Nancy Walsh, Staff Writer, MedPage Today
Published: September 01, 2011
When former No. 1 women's tennis star Venus Williams withdrew from the U.S. Open this week, she brought immediate attention to the little-known autoimmune disease Sjögren's syndrome, thought to afflict some 0.5% of adults.The disease is characterized by destruction of the exocrine glands, leading to excessive dryness of the mouth and eyes.But Sjögren's syndrome also is associated with symptoms such as debilitating fatigue and musculoskeletal problems that could seriously interfere with athletic performance.

"It's my suspicion that it may have been the systemic manifestations like fatigue and joint pain that have been troubling her and that could be difficult for a person trying to function at that very physically demanding level," Robert Spiera, MD, director of the vasculitis and scleroderma program at the Hospital for Special Surgery in New York City, told MedPage Today. Spiera has not been involved in Williams' treatment.

Earlier in the week Williams, 31, won a match in the tournament, held at the Billie Jean King National Tennis Center in Flushing, N.Y., but when she left the venue, after withdrawing on Wednesday, she said in a statement, "I enjoyed playing my first match here and wish I could continue, but right now I am unable to," according to the New York Times.

Steven Taylor, who heads the Sjögren's Syndrome Foundation, said in a statement, "On behalf of the four million Americans with Sjögren's, we applaud Venus for publicly stepping forward and shedding light on this serious autoimmune disease."

Diagnosing the disease can be challenging, and can involve salivary flow testing, salivary gland biopsy, and blood tests for autoantibodies such as rheumatoid factor, antinuclear antibodies, SSA and SSB antibodies.

Williams, who has been sidelined in recent months because of what was thought to be a viral illness, said she was "thankful to finally have a diagnosis." In fact, according to Taylor, the average time to diagnosis is 6.5 years after symptom onset.

The condition affects women far more than men, as is the case with most autoimmune diseases, and generally begins when patients are in their 40s.
"When patients present with complaints such as fatigue, clinicians need to be proactive and think beyond the common diagnoses like depression and thyroid disorders and ask about dry eyes and mouth," Spiera said.

Some similarities exist between Sjögren's syndrome and other autoimmune disorders such as rheumatoid arthritis and lupus, including articular, renal, and neurologic involvement.
For many patients, symptoms can be managed with products such as eye lubricants.
But for those with more severe manifestations, systemic medications such as anti-inflammatories, antimalarial drugs, and immunosuppressive agents may be needed.
Williams apparently is taking an oral medication that could take several months for its full effects to be seen, according to another report in the Times.

B cells are thought to play a crucial part in the development of Sjögren's syndrome, accumulating and becoming hyperactive in the exocrine glands and heightening immune antigenic responses.
For reasons that are not yet clear but which may involve B-cell proliferation and mutagenicity, in some patients the immune hyperactivity can evolve into a lymphoproliferative malignancy.
"Patients with Sjögren's have a risk of lymphoma that is as much as 40-fold higher than the general population," Spiera said.

Certain features of the disease seem to be associated with the development of lymphoma, such as bulky lymph or parotid gland enlargement, skin vasculitis, and low blood levels of complement.
"But the vast majority of patients with Sjögren's syndrome never develop lymphoma," Spiera said.
"Most patients with the disorder live very productive lives. Sjögren's does affect their quality of life, but there are strategies to help deal with their problems," he added.


From Reuters
FDA may get two more months to review new drugs
(Reuters) - U.S. regulators and the drug industry want to extend by two months the deadline for the Food and Drug Administration to approve or reject new drugs.
The extended timeline was tucked into the proposed deal the FDA forged with the prescription drug industry on the fees companies pay for drug reviews. The FDA posted the proposal on its website on Thursday.

The FDA said it would need an extra 60-day "filing date" before the clock starts ticking on its 10-month deadline to review new drugs, or six months for a priority review.
The new five-year agreement, which will be put out for public comment, comes as the FDA faces increased criticism from congressional Republicans and the industry for being too slow in approving new products, which they say stifles innovation and job creation.
"People are kind of scratching their heads" over the longer review time, said an industry source familiar with the negotiations on the user fees.

"But the idea is that FDA will use those two months to really prepare for the review ... so the hope is that it gives us more predictability and makes everything shorter in the long-run."
The Prescription Drug User Fee Act (PDUFA), first enacted in 1992, gives the FDA millions of dollars annually to review new products for the U.S. market in exchange for quicker approvals and other promises.

Congress must reauthorize the current PDUFA legislation before it expires in September 2012. The FDA's new fee agreement with industry, which would kick in at the beginning of 2013, would be part of the reauthorization legislation .

The fees system is controversial, with some critics contending they influence the FDA, which is supposed to protect the health and safety of consumers.
Currently, about a third of the agency's funding comes from makers of drugs and medical devices -- and that could grow if the FDA reaches a final agreement with generic drugmakers.
In 2010, the FDA collected $922 million in user fees out of a total budget of about $3.28 billion. The agreement with the prescription drug industry would increase user fees 6 percent over levels in 2012 for an estimated total of about $713 million in 2013, FDA Commissioner Margaret Hamburg said in Congressional testimony in late July.

The FDA also wants more flexibility on how it spends the money. Some of the fees will go toward drug safety, rare diseases and for training FDA staff in new technologies and science -- part of a broader push to improve the agency's scientific expertise.

"If you look at the original PDUFA, all of that went directly to just review processes," said Ryan Hohman, the director for communications and policy at Friends of Cancer Research, a think-tank and advocacy group.
"But the FDA and industry stepped back and recognized that in the economic environment, they need to have the increase in science or else they won't be able to approve these drugs at a speedy time for patients."

The FDA must still agree on the specifics of its user-fee program with the medical device industry, which started paying fees in 2002. It is also planning a new fee program with makers of generic drugs and 'biosimilars' -- copycat versions of brand-name biotech drugs.
(Editing by Karey Wutkowski and Andre Grenon)

From Pharmalot

By Ed Silverman
September 2nd, 2011
Once again, a web page is deemed problematic by the FDA. In a letter sent by the agency earlier this week, Pfizer was chastised because its Lipitor web page made misleading representations and suggestions about several other drugs. The issue came to light, by the way, thanks to the FDA ‘Bad Ad’ program, which encourages people to file complaints about troublesome promotions (see this)....... Continue Reading..

Cancer Research

Jennerex press release
Jennerex cheered by early efficacy data for cancer-killing virus
A small, mid-stage study of Jennerex's genetically engineered virus offered some important preliminary proof-of-concept data on its ability to zero in on cancer cells with just a single infusion. Reporting in Nature, investigators said biopsies confirmed the virus was replicating inside the tumors of 7 of the 8 people with metastatic cancers who were given the engineered dose, leaving healthy tissue untouched. Researchers noted several weeks after treatment the tumors in half of the group had stopped growing, indicating their cancers may have stabilized, and that in one case tumors appeared to shrink.

Why cancer cells change their appearance?

Like snakes, tumor cells shed their skin. Cancer is not a static disease but during its development the disease accumulates changes to evade natural defenses adapting to new environmental circumstances, protecting against chemotherapy and radiotherapy and invading neighboring organs, eventually causing metastasis.
Fondo de Investigaciones Sanitarias (FIS), Josef Steiner Cancer Research Foundation, Lilly Foundation, European Research Council Advanced Grant, Health Department of the Catalan Government, Instituto de Salud Carlos III, ICREA


Comprehensive Management of Liver Disease 
at the Montefiore Einstein Center for Transplantation
Friday, September 02, 2011
“The Marion Bessin Liver Research Center is a highly respected and internationally renowned research facility that performs revolutionary work in the fields of liver transplantation and stem cell research,” says Milan Kinkhabwala, M.D., Surgical Director of the Montefiore Einstein Center for Transplantation, Chief of the Division of Transplantation, Montefiore Medical Center, and professor of surgery, Albert Einstein College of Medicine. “The program needed a clinical arm to help advance the treatment of liver disease and provide direct benefits to patients. We brought together a team of highly trained hepatologists, hepatobiliary surgeons and gastroenterologists, and integrated those clinicians with the existing team of research professionals to create a truly interdisciplinary center featuring both clinical and research expertise that is dedicated to providing innovative, novel treatments for liver disease.”
Physicians are also involved in clinical trials utilizing Telaprevir, a new medication for treatment of viral hepatitis C........

Healthy You

Diet and hep C
Staying as healthy as possible will help you cope better with hep C. To help improve your health, eating a wide variety of food in the right balance is important. The following advice about diet and food has been developed by dietitians who work with hep C. It aims to dispel myths and help you to stay as healthy as possible.
Avoid restrictive or cleansing diets as there is little clinical or biological basis to support them. The bottom line is that if you don’t have serious liver damage (e.g. cirrhosis) there are no particular foods that you should seek or avoid because of your hep C. If you do have serious liver damage, speak to your specialist or doctor for dietary advice...Continue Reading..

The Low-Fat Con?
By Simon Donovan
Published: September 2, 2011
Posted in: Editorial, Nutrition
Products such as mayonnaise, cottage cheese and other dairy products often come in low-fat or reduced fat varieties. But what are reduced or low-fat products? In order for a food or product to be classified as low-fat it must contain fewer than 30% of its total calories from fat, in simple terms the product must be constitute less than 30% fat. Whilst reduced fat products do not have to meet set criteria with regards to their fat content, they must just contain less fat than their natural products. For products such as cheese and mayonnaise to be less than 30% fat requires a significant proportion of the fat to be removed. Common sense tells us that if we take something out we must put something back in to replace it. So what is replacing this fat? Yes, you have guessed, it is sugar..........Continue reading..

Osteoarthritis (OA)

Glucocorticoid treatment may prevent long-term damage to joints
Joint injury can result in irreversible damage of cartilage which, despite treatment and surgery, often eventually leads to osteoarthritis (OA) in later life. New research published in BioMed Central's open access journal Arthritis Research & Therapy demonstrates that short term treatment of damaged cartilage with glucocorticoids can reduce long term degenerative changes and may provide hope for prevention of OA after injury.

A normal joint is covered by a layer of cartilage containing proteoglycans such as aggrecan and lubricating fluid containing glycosaminoglycans (GAG) such as hyaluronic acid. In a double whammy, after injury proteoglycans and other molecules in cartilage begin to break down and the synthesis of these proteoglycans within cartilage is reduced. Additionally proinflammatory cytokines such as TNFα, IL-1β, and IL-6 are released into the synovial fluid after injury and further increase GAG loss from cartilage.

Using a 'worst-case scenario' system in which cartilage was subjected to mechanical injury and bombarded with immune system-stimulating bio-molecules (TNFα and IL-6) the glucocorticoid dexamethasone (DEX) was able to reduce GAG loss and restore proteoglycan synthesis levels to normal.

Prof Alan Grodzinsky from the MIT Center for Biomedical Engineering said, "Glucocorticoid injections are sometimes used to relieve the pain of established osteoarthritis, but there are concerns about long-term use. Our results suggest that short-term glucocorticoid treatment after joint injury may help restore components of cartilage to preinjury levels and consequently may prevent the long term changes which lead to osteoarthritis."

Thursday, September 1, 2011

Hepatitis C in Minority Populations

September issue of Gastroenterology

Hepatitis C in Minority Populations

These presentations were given at Digestive Disease Week 2011 in Chicago.

About 3.2 million people in the United States arechronically infected with hepatitis C virus (HCV), the leading cause of cirrhosis and hepatocellular carcinomaand the leading indication for liver transplant.

HCVprevalence is highest in minorities, especially black men,but blacks have poorer response to peginterferon/ribavirin than whites. VIRAHEP-C, astudy of black and white patients with genotype 1 HCV treated with peginterferon alfa-2a, found lower sustained virologic response(SVR) rates in blacks compared to whites(28% vs. 52%) (Gastroenterology 2006;131:470-7).

Blacks also have lower SVR to peg-interferonalfa-2b, and lower SVR when infected with HCV genotypes 2 and 3.

The impact of Hispanic ethnicity on HCV treatment response is largely unknown.

The LATINO study found significantly lower SVR(34%) to peginterferon/ribavirin in white Hispanics withHCV genotype 1 compared to non-Hispanic whites (49%)(N. Engl. J. Med. 2009;360:257-67). However, the LATINO results may not be generalizable, because inclusion/exclusion criteria were narrow, and investigators did not measure insulin resistance, which is linked to lower SVR andis prevalent in Hispanics.

One mechanism for poorer response of blacks and possibly Hispanics to peginterferon/ribavirin was elucidated recently. Genome-wide association studies in HCV-infected patients uncovered single nucleotide polymorphisms in IL28B (IFN-gamma-3 gene) that are strongly associated with race and SVR.

The favorable IL28B CC genotype occurs in highest frequency in East Asians and whites (and is associated with SVR above 80%), intermediate frequency in Hispanics, and lowest frequency in blacks (SVR 53%). In contrast, the unfavorable TT genotype is most frequent in blacks, and is associated with anSVR of 12%.

Investigators estimate that variable frequency of the IL28B C-allele explains half the racial differences in SVR to peginterferon/ribavirin.

We have entered a new era of HCV therapy with the recent approval of two direct acting antiviral (DAA) drugs, boceprevir and telaprevir. DAA use was linked to increased side effects, but DAA/peginterferon/ribavirin significantly improved SVR in patients withHCV genotype 1, and shortened treatmentin many patients.

Data on DAAs in minorities are limited, but promising. In every trial, addition of the DAA improved the SVR for all ethnic groups.

In ADVANCE, SVR in the telaprevir/peginterferon/ribavirin arms (69%-75%) was significantly higher than the peginterferon/ribavirin arm(44%) (N. Engl. J. Med. 2011;364:2405-16).
In blacks, SVRwith telaprevir/peginterferon/ribavirin (62%) was significantly higher than with peginterferon/ribavirin (25%).In SPRINT II, SVR was significantly higher in boceprevir/peginterferon/ribavirin arms (63%-66%) than in the peginterferon/ribavirin arm (37%). (N. Engl. J.Med. 2011;364:1195-206).

Among 159 blacks (14.4% ofpatients), SVR was 42%-53% in boceprevir/peginterferon/ribavirin arms compared to 23% in the peginterferon/ribavirin arm. In each DAA trial, blacks had lower SVR than whites, but the number of blacks was small, and statistical comparison between blacks andn on-blacks was not performed.

The impact of the IL28B genotype on responsivenessto the DAAs is unknown. Data from DAA trials suggest that IL28B genotype is a stronger predictor of response than race. However, the strongest predictor of responseis receiving DAA.
Triple therapy with DAA/peginterferon/ribavirin improves SVR for all ethnicities and IL28B genotypes, narrowing the SVR gap between groups.

Accordingly,the relative importance of the IL28B genotype may diminish, but further studies are needed to determine its role in HCV treatment paradigms.

As DAAs enter the marketplace, several unresolved issues relevant to minority populations remain. The impactof IL28B, race/ethnicity, and other host factors on treatment responsiveness must be explored in well-designed trials with larger representation of minorities. Innovative strategies are needed to improve minority recruitment into these trials, and care must be taken to ensure that minority patients with hepatitis C have equal access to DAAs.

■ANDREA EWING REID, M.D., M.P.H., is Program Director,Gastroenterology Training, Gastroenterology, Hepatology and Nutrition Section, Washington DC VA Medical Center.

Trial Supports Addition of Telaprevir for HCV Genotype 2

September issue of Gastroenterology

Trial Supports Addition of Telaprevir for HCV Genotype 2

Elsevier Global Medical News Adding telaprevir to the standard regimen of peginterferon-alfa and ribavirin reduced the time needed to attain decreased viral loads in genotype 2 hepatitis C virus infection, reported Dr. GrahamR. Foster and his colleagues in the September issue of Gastroenterology.

The drug was less effective in patients with genotype 3 hepatitis C virus (HCV),in the first study to assess use of telaprevir for treating these strains. Dr. Foster,of Queen Mary University of London,and colleagues looked at treatment-naivepatients with HCV genotypes 2 and 3 (23and 26 participants, respectively).Patients received either telaprevir monotherapy (750 mg every 8 hours), telaprevir plus peginterferon alfa-2a (180mcg/week) and ribavirin (400 mg twice daily),or placebo plus peginterferon/ribavirin for 15 days, followed by the standard peginterferon/ribavirin regimen for 22 or 24weeks.

On day 8 of treatment, the proportion of patients with undetectable HCV RNA was 0% in the telaprevir monotherapy group, 20% in the telaprevirplus peginterferon/ribavirin group,and 0% in the peginterferon/ribavirin only cohort. By day 15, the proportions were 0%, 40% (2 of 5 patients), and22% (2 of 9 patients), respectively.The median times to undetectableHCV RNA were 31, 12, and 43 days in thetelaprevir monotherapy group, the telaprevir plus peginterferon/ribavirin group, and the peginterferon/ribavirin only group.

Moreover, the proportions of patients with a sustained virologic response(SVR), defined as undetectable HCV RNA at end of treatment and 24weeks after final study medication, were56% in the monotherapy cohort (5 of 9patients), 100% in the dual telaprevir plus peginterferon/ribavirin group (5 of 5 patients),and 89% in the peginterferon/ribavirin-only group (8 of 9 patients).

There was less success among patients with genotype 3 of the disease. The median times to first undetectable HCV RNA result among these patients were 99, 43,and 29 days for the monotherapy cohort,the telaprevir plus peginterferon/ribavirin group, and the peginterferon/ribavirin only group, respectively. Likewise, the corresponding SVR rates were 50% (4/8),67% (6/9), and 44% (4/9), respectively.The most frequently reported adverse events were flu like illnesses and pruritis.

Of the five reported serious adverse events,only one – pneumonia – was considered related to the study medication, in this case, peginterferon/ribavirin. Based on theefficacy shown among treatment-naive patients, “the potential of telaprevir-based triple combination therapy in patients with HCV genotype 2 who have not responded to peginterferon/ribavirin should be explored,” said the authors.And while the drug’s poor performance among genotype 3 patients makes it “unlikely to have major clinical utility in this patient sub population,… for treatment-naive patients with genotype 2 HCV, studies to examine a shortened duration of therapy that includes telaprevir should be considered.”

The study was sponsored by Janssen Pharmaceuticals and Vertex Pharmaceuticals.

Several authors had financialrelationships with multiple pharmaceuticalcompanies, including Tibotec Pharmaceuticals.
Two investigators were alsoemployees of Tibotec or Janssen. ■

Sept 1 Hepatitis News Ticker

GI & Hepatology News-September

GI & Hepatology News is the official newspaper of the AGA Institute and provides the gastroenterologist with timely and relevant news and commentary about clinical developments and about the impact of health-care policy. The newspaper is led by an internationally renowned board of editors.GI & Hepatology News is published monthly and mailed to all U.S. members and available to all members online.
View Current Issue (VOL. 5 • NO. 9 • SEPTEMBER 2011):
Download; PDF Interactive Version

Bilateral Foot Necrosis Caused by Hepatitis C Virus–Induced Mixed Type II Cryoglobulinemia
Alejandro Velasco, Sameer Islam, Kenneth Nugent
Article Outline

A 52-year-old woman was admitted for increasing severe pain in her feet during the previous month. Her symptoms began 2 years earlier when she noticed skin discoloration and occasional blisters in her feet that became worse before admission. Her medical history included dyslipidemia and hepatitis C virus (HCV) infection incompletely treated 4 years earlier. On physical examination, she had livedo reticularis (Figure A) with purple skin discoloration and blisters on the dorsum of the feet. In addition, severe distal necrosis of the toes with diminished pedal pulses was seen (Figure B). Significant laboratory results included positive serum mixed cryoglobulin type II titer, elevated rheumatoid factor (127 IU/mL), low C3 and C4 levels, and an HCV RNA viral load of 153,000 IU/mL.

Skin biopsy of lower extremities confirmed leukocytoclastic vasculitis (Figure C). An arterial ultrasound of lower extremities showed mild-to-moderate plaques bilaterally with no significant stenosis. Angiographic studies showed aneurysms in the abdominal aorta and right common femoral artery. Clinical and laboratory findings were attributed to mixed cryoglobulinemia. The patient underwent bilateral amputation of lower extremities and treatment with pulse steroids.

Cryoglobulinemia can be detected in 36%–55% of patients infected with HCV, but only 3% develop vasculitic manifestations.1, 2 The most common clinical manifestations are cutaneous vasculitis, arthritis, peripheral neuropathy, and glomerulonephritis.2 Cutaneous vasculitis in mixed type II cryoglobulinemia is characterized by an orthostatic purpura in lower extremities caused by venous stasis and a nonspecific leukocytoclastic vasculitis with infiltration of skin, vessel walls, and microvascular thrombosis3; typically the presentation is not livedo or skin necrosis.4 The bilateral nature of the necrosis with insignificant arterial stenosis in this patient suggests diffuse systemic medium and small vessel disease. Endothelial dysfunction, atherosclerotic plaques, and vascular infiltration by immunocomplexes could cause this rapid presentation of bilateral foot necrosis.

The virologic response to antiviral therapy in HCV patients is not affected by the concurrent presentation of mixed cryoglobulinemia, and small studies show an improvement of cutaneous symptoms.3, 5, 6 Symptomatic response can be as high as 80% in patients receiving antiviral therapy, even when not associated with serologic response.7 However, the clinical remission is mostly limited to mild-to-moderate disease activity, and it is doubtful if it will improve symptoms in cases like ours with severe manifestations.
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Incidence of amoebic liver abscess had decreased in the USA
A study in September's issue of Liver International investigates the incidence, temporal trends and mortality with amoebic liver abscess in the USA.
Amoebic liver abscess may be associated with significant morbidity and mortality, but nationwide American data is unavailable.
Dr Stephen Congly and colleagues from Canada described amoebic liver abscess epidemiology and outcomes in USA from a population-based perspective.
Patients hospitalized with amoebic liver abscess between 1993 and 2007 were identified using the Nationwide Inpatient Sample. Patient characteristics, interventions and outcomes including mortality were determined.

The annual incidence was 1.4 per million population
Liver International

The annual incidence of amoebic liver abscess and temporal trends were determined using the negative binomial regression models.
Between 1993 and 2007, 848 hospitalizations for amoebic liver abscess, corresponding to ∼4100 hospitalizations nationwide, were identified.
The team found that the annual incidence was 1.4 per million population with a 2% average annual decline during this study.
The research team observed that most patients were hospitalized in western and southern states, and 48% were Hispanic.
The team found that males had the highest incidence rates.
The researchers noted that percutaneous and surgical drainage was required in 48% and 7% of patients, respectively.
Although length of stay, and hospital charges were substantial, in-hospital mortality was rare.
Females, patients 60 years or older, and those with 3 or more comorbidities, particularly malnutrition, had an increased risk of death.
Dr Congly's team concludes, "Amoebic liver abscess is rare and the incidence has decreased in USA."
"Young, Hispanic males in southwestern states are most frequently affected."
"Mortality caused by amoebic liver abscess is lower than what was reported previously."
Liver Int 2011: 31(8): 1191–119801 September 2011

Non-Invasive Markers for Hepatic Fibrosis *Full Text Available
Ancha Baranova, Priyanka Lal, Aybike Birerdinc, Zobair M YounossiBMC Gastroenterology 2011, 11:91 (17 August 2011)

'Hepatitis C has been accepted as not being a dirty word'
Sept 1
Educating inmates about hepatitis C is rewarding for Kim Mudd, Marie Hair, Jayne Dodd and Sharon Pyatt
Hepatitis C is curable. Yet, it is responsible for some 86,000 deaths in Europe and 9 million people are infected, according to the World Health Organization. Tackling this are four nurses at HMP Forest Bank in Greater Manchester who are testing, treating and educating prisoners.
Jayne Dodd, hepatitis specialist nurse for prisons in Greater Manchester, is responsible for assessing suitability for treatment as well as comprehensive care and monitoring of patients being treated. Marie Hair is the lead nurse and works with Kim Mudd, healthcare assistant, to screen and treat patients until they are discharged. Sharon Pyatt, primary care manager, accesses, facilitates and funds training for the nurses.
Recognised by WHO this year for a Best Practice Award, the team also received a Sodexo Services Star Award for continuous improvement in hepatitis C service. Since 2009, it has increased awareness and testing in the prison and throughout Greater Manchester
Continue Reading...


Tackling the spread of HIV in the UK
Terrence Higgins Trust is launching ‘Tackling the Spread of HIV in the UK’, a plan to bring down HIV transmission and reduce the growing financial burden on the NHS at a time it can least afford it.

AIDS vaccine research
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Dr David Cook, who is the Executive Vice President of IAVI, the International AIDS Vaccine Initiative, visited Sydney last week. He talks about the latest research into AIDS vaccines. Read Transcript


Cancer-stricken grandfather given just 12 months to live sees tumours killed in TWO DAYS after breakthrough treatment
By Jessica Satherley
Last updated at 12:51 PM on 1st September 2011
A cancer-stricken grandfather given just 12 months to live has undergone a breakthrough treatment which killed his tumours - in just two days.
Brian Brooks, 72, received the devastating prognosis after a random bowel screening test showed his colon and liver was riddled with cancer.

With nothing to lose, the father-of-two from Ely, Cambridgeshire, put himself forward for a trial therapy for liver cancer called Foxfire, spearheaded by Cancer Research UK's Bobby Moore Fund.

Great news: Brian Brooks (pictured with his wife Nicky) had his tumours killed in just two days by the new treatment

The radical treatment, called radioembolisation, places radioactive material inside blood vessels which deliver a dose of radiation directly into the liver.
Remarkably, his tumours were killed off after only two days of treatment - which meant doctors were then able to treat the cancer in his colon.
Experts now believe the breakthrough treatment could help treat thousands of cancer sufferers across Britain.

The Bobby Moore Fund was established by Stephanie Moore in 1993 in memory of her late husband Bobby. He was captain of the England team which won the World Cup and captained West Ham. He died from bowel cancer aged just 51.
Mr Brooks, of Ely, Cambridgeshire, is one of only 40 Britons to be treated in the Foxfire trial and one of the first to be given the all-clear.
He is now in remission - and describes his treatment as a ‘miracle’.

He said: ‘I was given a death sentence, it's a very difficult thing to get your head around.
'My family were devastated and one of the worst things for me was thinking I may not see my three year-old granddaughter grow up.
'But they never gave up hope and were tremendously supportive, that helped me through the treatment.
'To be told you have 12 months to live and then to have completely healed 12 months down the line, we believe is a miracle.
'Obviously there is always the risk that the cancer can come back but I am now in remission and that is something that the doctors did not believe was possible.'

His wife, Nicky, 67, said: 'It was completely random - Brian's name was picked and he underwent the trial alongside his chemotherapy.
'We've just had the results back and my doctors can't believe its success - they say they are astonished.
'If we hadn't been informed about this trial, Brian would not be here today.'
Brian, a retired boarding kennel owner from Ely, Cambridgeshire, went for a random bowel screening test at Addenbrooke's Hospital on September 6, 2010.
The scans showed a tumour in his colon and others in his liver - which doctors told him they were unable to operate on.
Brian and Nicky were forced to break the news to their son Iain, 45, daughter Joanne, 40, and grandson William, 3.
But they were given hope when Brian was accepted onto the Foxfire trial, to try radioembolisation therapy, which is only available on the NHS to patients treated the second time around.

Brian was given the treatment at Addenbrooke's Hospital in Cambridge and went for the first stage, when doctors plotted the blood flow over his liver, on November 17.
The following day he was given the second part of the treatment which involved a blast of nuclear spores into the blood cells which were feeding the tumour.

The grandfather-of-one was treated at Addenbrooke's Hospital in Cambridge
Four months later Brian was told the tumours in his liver had completely disappeared and he could now undergo chemotherapy to shrink the tumour in his colon.
He began 11 sessions of traditional chemotherapy to shrink the tumour in his colon, which doctors removed seven weeks ago.
Brian added: 'I remember seeing the results of my scan and reading 'Complete resolution of all liver tumours' - it was incredible.
'My family and I are so grateful to the Bobby Moore Fund, Cancer UK and of cause the wonderful doctors at Addenbrookes.'

Radioembolisation is a combination of radiation therapy and a procedure called embolisation to treat cancer of the liver.

Unlike traditional radiotherapy, which is directed at the tumour from outside the body, this delivers a high dose of radiation from inside the diseased area of the body.
Tiny resin beads called microspheres are placed inside the blood vessels that feed a tumour to block the supply of blood to the cancer cells.

Once these radioactive microspheres become lodged at the tumour site they deliver a high dose of radiation with minimal damage to healthy cells.
The trial co-ordinated by Oxford University was launched in February 2010 and 40 patients have so far enrolled.

Worldwide 800 patients have been treated, half receiving chemotherapy and radioembolisation and the other 400 given chemotherapy alone.

Kate Law, Cancer Research UK's director of clinical trials said: 'Without clinical trials like Foxfire, we wouldn't be able to improve techniques for cancer that are hard to treat.
'It's a promising trial and we look forward to following its progress and seeing the results.'
Explore more:
Oxford University

UPDATE 1-Delcath says colorectal cancer treatment not effective
Thu Sep 1, 2011 7:22am EDT
* Says will continue to study the efficacy
* Says will start a new mid-stage in 2012 second half (Follows alerts)
Sept 1 (Reuters) - Delcath Systems Inc said its experimental cancer treatment failed to show any efficacy in patients with colorectal cancer in a mid-stage trial.
The company said its chemosaturation system, which was using melphalan for the treatment, did not prove to be efficacious as the patients had been heavily pre-treated with numerous other chemotherapies.

The fresh results come more than a week after the same treatment showed strong efficacy in treating primary liver cancer patients.

Delcath said it would also initiate a new mid-stage single-arm study in the second half of 2012.
"We will continue to study the efficacy of our chemosaturation system in this patient population that currently has few treatment options," Chief Executive Eamonn Hobbs said.
Sixteen patients with very late stage colorectal cancer, which had spread to the liver, were recruited into this arm of the trial, the company said.
The study included four patient cohorts -- hepatobiliary cancer, metastatic cancer of neuroendocrine, ocular or cutaneous melanoma, and colorectal cancer.
Delcath said the safety profile of the chemosaturation system was consistent with a previous late-stage melanoma trial.
Shares of the New York-based company closed at $4.14 on Wednesday on Nasdaq.
(Reporting by Kavyanjali Kaushik in Bangalore; Editing by Saumyadeb Chakrabarty)

Researchers report new understanding of role of telomeres in tumor growth
Study published in The American Journal of Pathology
Philadelphia, PA, September 1, 2011 –
The first report of the presence of alternative lengthening of telomeres (ALT) in cancers arising from the bladder, cervix, endometrium, esophagus, gallbladder, liver, and lung was published today in The American Journal of Pathology. The presence of ALT in carcinomas can be used as a diagnostic marker and has implications for the development of anti-cancer drug therapies.

Telomeres are nucleoprotein complexes located at the ends of chromosomes. During normal cell division, these telomeres become shorter with each division, potentially resulting in cell death. In some cancers, however, this shortening is counteracted by the ALT mechanism, thus allowing the unlimited growth of the cancer cells.

"The present study offers a springboard to guide future investigations in larger cohorts that specifically focus on the tumor types exhibiting ALT to more precisely determine the prevalence and potential prognostic value of this phenotype," commented lead investigator Christopher Heaphy, PhD, a postdoctoral research fellow at The Johns Hopkins School of Medicine.
"These results may have therapeutic consequences, given that cancers using the ALT pathway are predicted to be resistant to anti-telomerase therapies, some of which have entered phase I/II clinical trials. Further understanding of the molecular mechanisms of ALT will be paramount in designing novel anti-cancer therapeutics targeting cancers utilizing the ALT pathway," observed corresponding author Alan K. Meeker, PhD, Assistant Professor of Pathology at Johns Hopkins.

Meeker and co-investigators have assessed the prevalence of the ALT mechanism in a wide range of human cancer subtypes. Analyzing 6,110 tumor samples from 94 different cancer subtypes, 541 benign neoplasms, and 264 normal tissue samples, researchers found that the overall prevalence of the ALT phenotype was 3.73%. It was not observed in benign neoplasms or normal tissues.

Additionally, this is the first report of ALT in medulloblastomas, oligodendrogliomas, meningiomas, schwannomas, and pediatric glioblastoma multiformes.
The authors also note that they were able to identify many tumor types that apparently may not use the ALT pathway for telomere maintenance. In particular, they assessed hundreds of cases of adenocarcinomas arising from the prostate, colon, pancreas, or small intestine and did not observe a single ALT-positive tumor.

Previous studies have shown associations between ALT status and prognosis in some tumor types. The authors suggest that further studies are warranted to assess the potential prognostic significance and unique biology of ALT-positive tumors.
The article is "Prevalence of the Alternative Lengthening of Telomeres Telomere Maintenance Mechanism in Human Cancer Subtypes" by Christopher M. Heaphy, Andrea P. Subhawong, Seung-Mo Hong, Michael G. Goggins, Elizabeth A. Montgomery, Edward Gabrielson, George J. Netto, Jonathan I. Epstein, Tamara L. Lotan, William H. Westra, Ie-Ming Shih, Christine A. Iacobuzio-Donahue, Anirban Maitra, Qing K. Li, Charles G. Eberhart, Janis M. Taube, Dinesh Rakheja, Robert J. Kurman, T.C. Wu, Richard B. Roden, Pedram Argani, Angelo M. De Marzo, Luigi Terracciano, Michael Torbenson, and Alan K. Meeker. (doi: 10.1016/j.ajpath.2011.06.018). It will appear in The American Journal of Pathology, Volume 179, Issue 4 (October 2011) published by Elsevier.

Cancer-killing viruses zero in on tumor cells
Doctors have known for nearly a century that when cancer patients catch a virus the infection can help to beat back their tumors. But developing therapies hinged upon this idea has not been easy. Researchers first have to engineer the viruses to discriminately attack only the cancer cells. Then the virus has to actually reach those tumor cells and kill them. Despite these barriers, research has plunged forward, with several viruses in late-stage clinical development (see ‘Recent deal highlights hopes for cancer-killing viruses’).

Clinicians typically inject these so-called ‘oncolytic viruses’ into the tumors themselves using a syringe. But this delivery approach lacks precision. Thus, researchers have long sought cancer-killing viruses that can hone in on their own on cancerous cells while leaving healthy tissue intact. (Scientists are similarly trying to develop bacteria that serve the same purpose, as we reported in March.) Now, for the first time, researchers have engineered a virus that, when injected into people’s bloodstreams, preferentially attacks only cancer cells.
“This data set really puts oncolytic virotherapy on the map as a very, very promising experimental approach to the systemic treatment of metastatic cancer,” Stephen Russell, director of the molecular medicine program at the Mayo Clinic in Rochester, Minnesota who was not involved with the research, wrote in an email

Family history of cancer
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Researchers in the US investigated the importance for doctors of obtaining knowledge of a family's cancer history to assess risks and initiate appropriate early interventions, that is screening recommendations, etc. Read Transcript

A step toward a saliva test for cancer
American Chemical Society 242nd National Meeting & Exposition;
A new saliva test can measure the amount of potential carcinogens stuck to a person's DNA -- interfering with the action of genes involved in health and disease -- and could lead to a commercial test to help determine risks for cancer and other diseases, scientists reported here today during the 242nd National Meeting & Exposition of the American Chemical Society (ACS).


Expert Discussion: The Continuing Challenge of Effectively Managing Type 2 Diabetes, Part I
Defining Prediabetes and Diabetes
Editor's Note: This is the first in a two-part series on the detection and treatment of type 2 diabetes mellitus focused on the educational needs of physicians. It is based on a live expert discussion, audio segments of which are available online at Part two of the series will appear in our September issue.

Infectious Disease & Viruses

The New Generation of Microbe Hunters
Gina Kolata(The New York Times, August 29, 2011)
"New methods of quickly sequencing entire microbial genomes are revolutionizing the field [microbiology]...Today researchers can sequence the DNA that constitutes a micro-organism’s genome in a few days or even, with the latest equipment, a day. (Analyzing it takes a bit longer, though.) They can simultaneously get sequences of all the microbes on a tooth or in saliva or in a sample of sewage. And the cost has dropped to about $1,000 per genome, from more than $1 million…One group [of molecular epidemiologists] is starting to develop what it calls disease weather maps. The idea is to get swabs or samples from sewage treatment plants or places like subways or hospitals and quickly sequence the genomes of all the micro-organisms. That will tell them exactly what bacteria and viruses are present and how prevalent they are...[and] take precautions against ones that are starting to emerge…Others are sequencing bacterial genomes to find where diseases originated."
Continue Reading..


Vertex Scores Big With Hepatitis Drug
The company's medication is outselling its rival
Aug 31, 2011, 12:20 pm EDT By Barry Cohen, Health Care Writer
Physicians and patients evidently like the advantages Incivek has over Victrelis, including data showing the Vertex drug had nearly an 80% cure rate and offers the possibility of even shorter treatment. In addition, Incivek is considered easier to use
Continue Reading...

Indians sitting ducks as drug trials turn fatal
In last 4 yrs, 1,725 persons have died in clinical trials; weak law compounds risks
Aditi Tandon/TNSTribune News Service
New Delhi, August 7
For the first time since 2010 when six tribal girls from Gujarat and Andhra Pradesh involved in the clinical trials of anti-cervical cancer HPV vaccine died, the government has admitted that 1,725 persons have lost their lives to drug trials in the last four years.
The number of deaths has risen from 132 in 2007 and 288 in 2008 to 637 in 2009 and 668 last year, indicating the complete ineffectiveness of regulatory controls over the $400 million sector. Last year, the government gave compensation in just 22 cases out of the 668 that resulted in deaths due to “serious adverse events” during drug trials, Health Minister Ghulam Nabi Azad told Parliament this week.

Stem Cells

Stem cell properties of hepatoma cells *Full Text Available
BMC Gastroenterology 2011, 11:71
Tumor spheres produced from hepatoma cell lines cultured in stem cell conditioned medium exhibit liver cancer stem cell (CSC) properties, and the CSL-independent Notch signalling pathway may play a role in the differentiation and propagation of liver CSCs.

Parents in India Bank on Stem-cells, Not the 'Tooth Fairy'
Stephanie Nolen
"In India, a fascination with stem-cell medicine combined with a growing demographic of affluent parents...have consumerized the stem-cell banking industry like nowhere else…India has no laws, and only unenforceable guidelines on what stem-cell research is permitted...The Indian stem-cell industry…is worth an estimated $500-million a year. As a consequence, there is a comparatively high level of awareness of stem-cell medicine in the general population…At the same time, as technological processes for the preservation of cells are 'indigenized,' they are becoming considerably cheaper to operate in India than they are in the West. That, combined with the sheer size of the Indian market, makes a practice such as banking baby teeth or menstrual cells suddenly feasible as a mainstream pursuit."
Continue Reading..

Pioneering UK stem cell trial passes safety test
By Paul Sandle
LONDON Thu Sep 1, 2011 4:25am EDT
LONDON (Reuters) - A pioneering clinical trial to inject stem cells into the brains of patients disabled by stroke has been cleared to progress to the next stage after the treatment raised no safety concerns in the first three candidates.
ReNeuron Group PLC, the British biotech behind the trial, said the independent Data Safety Monitoring Board had reviewed safety data from its ReN001 stem cell therapy and recommended the trial advance to the higher dose.
"Data from the laboratory safety tests, neurological examinations and neurofunctional tests conducted thus far indicate that the ReN001 treatment is safe and well-tolerated at the initial dose," the company said in a statement on Thursday.

The procedure involves injecting ReNeuron's neural stem cells into patients' brains in the hope they will repair areas damaged by stroke, thereby improving both mental and physical function.
It uses stem cells derived from human fetuses rather than embryos, which were used in a stem cell trial to treat patients with spinal cord injuries by Geron Corp of the United States.
ReNeuron's chief executive Michael Hunt said the clearance was an important milestone, and the preliminary data also backed up the group's other therapeutic programs using the CTX neural stem cell line that formed the basis of the ReN001 stroke treatment.

The principal investigator for the trial, Keith Muir from the University of Glasgow's Institute of Neuroscience and Psychology, said he looked forward to evaluating further patients at a higher dose.
"ReN001 has the potential to address a very significant unmet medical need in disabled stroke patients and I am pleased that our team is involved in this pioneering clinical trial," he said.
Shares in ReNeuron rose 3.3 percent in early trade.

Analysts at Matrix said ReNeuron was making excellent progress within the trial, which it believed could set the company apart from other stem-cell companies in the field, given the other advantages it has in terms of manufacturing, scalability and the off-the-shelf nature of the technology.

"The data generated thus far are all the more remarkable, in our view, given the fact that the patients receiving the cells have not been subject to immunosuppression" they said in a note.
"We look forward to the data from the next cohort within this study."
(Reporting by Paul Sandle; Editing by Helen Massy-Beresford)

US Health Care

Who Are the Most Powerful People in American Medicine?

Medical Clinics in Retail Settings Are Booming
Mary Brophy Marcus
"Insured patients are increasingly turning to the convenience of drugstore clinics…and other medical resources outside the traditional doctor's office setting when they can't schedule day-of appointments with their primary-care provider. Some without health insurance say they find them a faster, less pricey alternative to urgent care or emergency room visits…The satellite medical suites address acute, but not typically life-threatening conditions such as strep throat, flu symptoms and bladder infections. Many offer vaccinations, and sports and camp physicals as well…There are about 1,250 retail-based convenient care clinics in the USA. Two-thirds are in drug stores and one-third are in retail settings…and supermarket chains, says Tine Hansen-Turton, executive director of the Convenient Care Association in Philadelphia. The growth has been significant, she says: in 2006, there were only 175 such locations. Health insurers are getting in on the game, too... Continue Reading..

Disease exposure via medical devices a growing concern, CDC says
Milwaukee Journal-Sentinal
Diabetic patients who may have been exposed to blood-borne diseases at a Madison-based clinic are now getting tested for hepatitis and HIV.

In Case You Missed It

One Word Can Save Your Life: No!
Aug 14, 2011 10:00 AM EDT - Newsweek Cover Story
New research shows how some common tests and procedures aren’t just expensive, but can do more harm than good.

"Many doctors don't seem to be getting the message about useless and harmful health care. Medicare pays them more than $100 million a year for screening colonoscopies; some 40 percent are for people in whom they will almost certainly harm more than help. Arthroscopic knee surgery for osteoarthritis is performed about 650,000 times a year; studies show that it, too, is no more effective than placebo treatment, yet taxpayers and private insurers pay for it. And although several large studies, including the Occluded Artery Trial in 2006, have shown that inserting a stent to prop open a blocked artery more than 24 hours after a heart attack does not improve survival rates or reduce the risk of another coronary compared with drugs alone, the practice continues at a rate of 100,000 such procedures a year, estimate researchers led by Dr. Judith Hochman, a cardiologist at New York University. "We're killing more people than we're saving with these procedures," says UT's Goodwin. "It's as simple as that."... Continue Reading..

VA awards new contract for debunked PTSD drug
By Bob Brewin 08/25/2011
The Veterans Affairs Department continues to issue contracts to purchase an anti-psychotic drug to treat post-traumatic stress disorder despite research showing the drug, risperidone, is no more effective than a placebo.
Nextgov reported Aug. 22 that VA spent $717 million over the past decade to purchase risperidone, the generic name for Risperdal, a second-generation anti-psychotic drug originally developed by the Janssen Pharmaceuticals division of Johnson & Johnson to treat severe mental conditions such as schizophrenia and bipolar disorder.
VA doctors prescribe the drug to treat PTSD, but a study by department researchers published Aug. 2 in the Journal of the American Medical Association concluded, "treatment with risperidone compared with placebo did not reduce PTSD symptoms."
Despite these findings, on Aug. 11, VA awarded a contract to Mylan Pharmaceuticals Inc. for more than 200,000 bottles of risperidone containing more than 20 million pills in multiple dosages. The announcement of the contract to the Morgantown, W.V., generic drug manufacturer did not provide a dollar value for the contract.... Continue Reading....

Complementary and Alternative Medicine

Ask UNF: Are dietary supplements safe and necessary?
Posted: September 1, 2011
A dietary supplement is a product taken by mouth that may include vitamins, minerals, herbs or other botanicals, amino acids and substances such as enzymes, organ tissues, glandulars and metabolites. Judy Rodriguez, chair of the Department of Nutrition and Dietetics at the University of North Florida, discusses supplements, their safety and whether they're necessary in our diet.

What are some things I should consider before taking dietary supplements?
It's important to remember that dietary supplements are only meant to be supplements and because they're under the general umbrella of foods, not drugs, they don't have to be tested for safety prior to being put on the market as drugs do. Although the manufacturer is responsible for making sure dietary supplement products are safe before putting them on the market, the Federal Drug Administration doesn't approve dietary supplements for safety. Once a product is on the market, however, the FDA can recall it, if it's shown to be unsafe.

Should everyone take a supplement?
It isn't necessary for everyone to take a supplement, but it's necessary to make healthy food choices. A multivitamin or specific supplement may be useful for people who are on a calorie-restricted diet, vegetarians, trying to get pregnant or are pregnant or breastfeeding, post-menopausal, at risk for osteoporosis, have had digestive tract surgery or a specific medical condition (such as lactose intolerance, chronic diarrhea or a food allergy). Consult a physician and registered dietitian to find out which supplement is most appropriate for you.

Are all natural supplements safe?
No. Consumer Reports has identified some hazardous supplements, including androstenedione (or andro, used by athletes for body-building); aristolochic acid (used in Chinese medicine for eczema and backaches); bitter orange and germander (used for weight loss); chaparral (used as a cancer cure); and comfrey (a green tea for stomach ulcers). Other dangerous supplements are kava kava and skullcap (used for anxiety); lobelia (popular for asthma and bronchitis); organ/glandular extracts (used to treat hepatitis C and other ailments); pennyroyal oil (used as an insect repellent and sometimes ingested for other ailments); and yohimbe (referred to as a men's aphrodisiac).

The hazardous side effects depend on the supplement and dose but may include abdominal tenderness, difficulty breathing, convulsions, rapid heart rates, heartbeat irregularities, heart attacks, blood pressure changes, nerve damage, irreversible abnormal liver function or damage, kidney failure and even death.

What things should I consider if I want to take a supplement?
You should consider whether it may be more effective to improve your
overall dietary behaviors, if you are in one of the categories listed above; the costs of additional supplements, if you are taking other medications that may contraindicate the consumption of the supplement; and the time and effort required to take the supplement. Consult a physician and registered dietitian.

Where can I get information about supplements?
To find a local registered dietitian, go to and the National Center for Complementary and Alternative Medicine at for information about different supplements.

Ask UNF is a monthly column that features the expertise of University of North Florida faculty and staff. If you have a question about this topic, contact Rodriguez at
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Fish oil
Fish oil is LIKELY SAFE for most people, including pregnant and breast-feeding women, when taken in low doses (3 grams or less per day).Fish oil can cause side effects including belching, bad breath, heartburn, nausea, loose stools, rash, and nosebleeds. Taking fish oil supplements with meals or freezing them can often decrease these side effects.Taking high doses of fish oil is


Taking more than 3 grams per day might keep blood from clotting and can increase the chance of bleeding.
High doses of fish oil might also reduce the immune system’s activity, reducing the body’s ability to fight infection. This is a special concern for people taking medications to reduce their immune system’s activity (HIV/AIDS patients, for example) and the elderly.
Taking fish oil supplements in larger amounts can increase levels of the “bad” LDL cholesterol in some people. You will need blood tests periodically to ensure LDL cholesterols do not become too high.
Some fish meats (especially shark, king mackerel, and farm-raised salmon) can be contaminated with mercury and other industrial and environmental chemicals, but fish oil supplements typically do not contain these contaminants.

Special precautions & warnings:Liver disease: Fish oil might increase the risk of bleeding.

Diabetes: There is some concern that taking high doses of fish oil might make the control of blood sugar more difficult.

Vitamin E
Fish oil can reduce vitamin E levels. Researchers aren't sure whether fish oil keeps vitamin E from being absorbed from food or whether it causes the body to use up vitamin E faster than it should... Continue Reading..

How acceptable is fish oil?
listen now download audio
Researchers at Flinders University in Adelaide have investigated the acceptability of fish oil, particularly by older adults.

This transcript was typed from a recording of the program. The ABC cannot guarantee its complete accuracy because of the possibility of mishearing and occasional difficulty in identifying speakers.

Norman Swan: Now there's no question that fish are good for your diet and that fish oil has therapeutic benefits in its own right but usually at massive doses compared to what's in your grilled flathead or ocean trout regardless of the size of the portion.
Alison Yaxley is in the Nutrition and Dietetics Department at Flinders University in Adelaide and she's been testing how acceptable fish oil is as oil rather than wrapped up in capsules.

Alison Yaxley: Conditions which cause the body to have a higher level of inflammation are really common in older adults and these conditions are likely to benefit from the use of fish oil. To reduce inflammation it's necessary to have a high dose of fish oil. In order to get such a dose you would need to be taking something like 10 capsules a day. So in older adults because they commonly don't take their medication well anyway we needed to be sure that they would actually take a dosage that was that high.

Norman Swan: And the capsules are expensive and the oil is cheap.
Alison Yaxley: Yes, fish oil liquid is much, much cheaper as you say.

Norman Swan: So your question was would they take it if you offered it to them?
Alison Yaxley: Our question was would they take it, what were the frequency and the extent of the side effects, so what were they and how often did they happen and what was the short term acceptability?

Norman Swan: And what was the comparator?
Alison Yaxley: We had a range of different concentrations of fish oil, we had one group of 50 which took four different concentrations of fish oil, and we had one group of 50 which took only one which contained no fish oil, in order to tell if they could actually tell the difference between some fish oil and no fish oil.

Norman Swan: And that was olive oil was it, the dummy oil?
Alison Yaxley: Yes, we used extra light olive oil, there were a couple of reasons for this. One was it has very, very little taste and also because it contains very few of the chemicals which produce Omega 3 fatty acids.

Norman Swan: And what sort of dosage are we talking about here that's believed to be necessary in terms of the oil to get say arthritis helped or maybe your heart quelled?
Alison Yaxley: The evidence shows that as little as 1 gram a day can actually make an improvement to coronary heart disease but in order to improve inflammation patients are commonly asked to take 15 mls of fish oil to reduce their rheumatoid arthritis for example.

Norman Swan: And what does that translate to in grams?
Alison Yaxley: That's approximately 10 grams of Omega 3 fatty acids which is around where our 10 capsules would be

Norman Swan: And what did you find?
Alison Yaxley: In the multiple samples these participants were asked to consume approximately 200 mls of liquid so that was fish oil and orange juice and water over a very short period of time. And consequently there were almost 25% of them reported side effects when we asked them 24 hours after the sample. But none of those participants said that that would stop them taking it.

Norman Swan: And what sort of side effects did they complain of apart from the taste?
Alison Yaxley: They were mostly minor. There would be a fishy aftertaste that some of them had, a couple of people said that they experienced looser bowels than would be normal but again none of them said that that would stop them from taking fish oil in the longer term.

Norman Swan: And that was different from the placebo group from the olive oil group?
Alison Yaxley: From the group that tasted one single sample so it wasn't that they all had the olive oil, it was that there was a possibility that they could have had olive oil, they could have had a 10% or 40% or 100% dilution of fish oil and olive oil. Of that group there were very few, only one person said they had any unpleasant taste and 4 people reported side effects. Two of which said that that would stop them taking fish oil in the longer term. The interesting thing about that was that one of those participants who reported a side effect actually had a controlled sample so they reported that they had fishy aftertaste and fishy burps but they didn't actually take any fish oil in their sample.

Norman Swan: And was there a difference in symptoms in concentrations when you gave them the 100% fish oil compared to say the 25%?
Alison Yaxley: No, perception is very important and there's evidence that they are affected by non smell and non taste stimuli as a result of what other people say about fish oil. Somebody's neighbour might be taking it and say it's disgusting and then that would put that person off taking it.

Norman Swan: And lead them to have certain expectations about what to experience when they take it. Did they all have just have one dose or did you ask them to take it for a few weeks?
Alison Yaxley: No, no, it was a cross sectional one dose one time point study. Part of it was to see if we could actually get them to take it at all. Quite a number of people said they wouldn't even try to take it. They had a very negative perception of what fish oil would be like even though they'd never tasted it. People over 60 -

Norman Swan: The remember cod liver oil at school.
Alison Yaxley: Exactly, so that was their lasting memory of a fishy oil. It's relatively recently that marketing of fish oil has been such that they have acknowledged the fact that it has a fishy taste and they are masking it with fruit flavours and a much more positive image.

Norman Swan: So you found that there are side effects, not major, they're not all confined to fish oil, people can take a placebo and get the side effects, but it didn't seem to put them off once they'd actually understood a bit about fish oil. Where to next?
Alison Yaxley: Well we wanted to do this study because our research group wanted to do a much larger study in patients with inflammatory conditions but we obviously needed to be sure that they would take the fish oil. So after doing this study we were able to get funding from the National Health and Medical Research Council to conduct a much larger study with patients with fish oil. We believe that the sheer volume of the fish oil that we asked these patients, the 50 in the multiple sample group, we asked them to take a very large amount and we believe that the incidence of side effects at roughly 25% was mainly due to the actual volume that we asked them to take. So we would foresee that side effects in practice would be much more in line with the single sample group which was very, very minimal.

Norman Swan: Alison Yaxley is a dietitian at Flinders University in Adelaide.
Yaxley A et al. Testing the acceptability of liquid fish oil in older adults. Asia Pc J Clin Nutr 2011;20(2):175-179

Healthy You

2011/2012 Flu shot guidelines
Dr. Lisa Dana
posted: 08/31/2011, 10:47 pm
The CDC(Centers for Disease Control) is recommending the flu vaccine for all persons aged 6 months of age and older. The flu is a viral illness caused by influenzae.
Symptoms of the flu include fever, cough, runny nose, chills, sore throat, headache, muscle aches, congestion and fatigue. Symptoms can range from mild to severe. Secondary infections and complications from the flu include pneumonia, bronchitis and other serious systemic illnesses.
Young children, the elderly, pregnant women and persons with certain chronic illnesses are more likely to get seriously ill from the flu. Everyone over the age of 6 months should receive the flu vaccine but the CDC believes it is very important for the following groups to be vaccinated:
Pregnant women
Children younger than 5, but especially children younger than 2 years old
People 50 years of age and older
People of any age with certain chronic medical conditions
People who live in nursing homes and other long-term care facilities
People who live with or care for those at high risk for complications from flu, including:Health care workers
Household contacts of persons at high risk for complications from the flu
Household contacts and out of home caregivers of children less than 6 months of age (these children are too young to be vaccinated)

Children under the age of 9 who did not receive a flu vaccine during the 2010/2011 season will need to receive two flu vaccines. If your child needs two vaccines this year, then the two vaccines should be seperated by 4 weeks.
The flu vaccine is offered in two different forms this year. You can receive the injectable killed vaccine or the live attenuated nasal flu mist vaccine. In our office, we offer the nasal flu mist as well as the flu vaccine injection.

The live attenuated nasal flu mist is available to persons between the ages of 2 – 49 years of age. Certain medical conditions restrict the use of the nasal flu mist. Patients with asthma, certain chronic medical conditions and patients who are immunocompromised or who are in close contact with immunocompromised people may not receive the nasal flu mist. Pregnant women and persons on long term aspirin therapy may also not receive this vaccine. Ask your doctor if the flu mist is right for you and your family.

The killed injectable flu vaccine can be given to persons over the age of 6 months.

Contraindications to the injectable flu vaccine include:
1. A history of Guillian-Barre ( a severe paralytic illness)2. Egg allergy 3. moderate or severe illness at the time of vaccine
You should receive the flu vaccine as soon as it is available. You can get the flu at any time, but most cases occur between October and May. The vaccine that you receive now will help protect you throughout the flu season.
The advice provided in this blog is for informational purposes only and is not a substitute for medical diagnosis, advice or treatment for specific medical conditions
Sources: SF Department of Public Health, CDC


Egg Farms Rack Up ViolationsFDA finds unsanitary conditions, keeps key data secret
Clark Kauffman(The Des Moines Register, August 28, 2011)
"One year after 1,900 people were sickened and a half-billion Iowa eggs were recalled, government inspectors continue to find unsanitary conditions and inadequate protections against salmonella on Iowa’s egg farms…Despite new federal regulations intended to give consumers greater protection against food-borne illnesses, government oversight of egg production remains a clumsy patchwork of state and federal laws. Among the gaps in the system: Inspections at egg farms are announced days in advance…and they are still based partly on the honor system, with government officials doing little on-site testing for salmonella. Federal inspectors review the companies’ self-reported, in-house test results, even though the laboratories that perform those tests are not required to be licensed or accredited. Penalties for health and safety violations that could lead to salmonella poisoning are nonexistent at both the state and federal levels…Iowa’s egg producers are required to test for salmonella, but they are not required to report any positive test results to either the state or the FDA…In recent months, however, the agency has said that long-awaited federal regulations are significantly reducing the risk of salmonella infections. The agency is inspecting many egg production facilities for the first time and now has the power to recall food products rather than rely on the producers to do so voluntarily…Iowa has been the No. 1 egg-producing state in the nation for the past 10 years…Analysts have attributed Iowa’s growth in egg production to low feed costs and an industry-friendly environment…Iowa exercises almost no oversight of egg production, leaving that job to the federal government…Today, the U.S. Department of Agriculture [USDA] oversees the health of chickens, while the FDA is responsible for whole eggs. Oversight shifts back to the USDA when it comes to transportation of whole eggs…but the FDA oversees the storage of eggs at the retail level. The USDA grades eggs in production facilities, but health inspections in those same facilities falls to the FDA, which, until last year, had no rules or standards to enforce…Consumers, meanwhile, took comfort in buying eggs with the distinctive shield logo of the U.S. Department of Agriculture, unaware that it signified only that the eggs had been graded for size, not inspected for safety or quality."
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