RxPG News : Gastroenterology

Weight loss by targeting satiety hormone

Sat, 27 Aug 2011 19:40:40 PST

( from http://www.rxpgnews.com ) The number of people who are obese and suffer one or more of its associated health problems (including type 2 diabetes) is escalating dramatically. Researchers are seeking to identify new targets for therapeutics that could limit appetite and thereby obesity. A team of researchers, led by Scott Waldman, at Thomas Jefferson University, Philadelphia, has now uncovered one such potential target by studying the molecular control of appetite in mice.

Guanylyl cyclase 2C (GUCY2C) is a transmembrane receptor that makes cGMP in response to the paracrine hormones guanylin and uroguanylin, which regulate epithelial cell dynamics along the crypt-villus axis. The researchers showed that silencing of GUCY2C in mice disrupts satiation, resulting in hyperphagia. This caused obesity and metabolic syndrome. In the study, Waldman and colleagues found that nutrient intake by mice caused cells in their gut to secrete the precursor of the hormone uroguanylin (prouroguanylin) into the blood. This travelled around the blood and was converted to uroguanylin in a region of the brain known as the hypothalamus, which is well known to be involved in decreasing appetite. The active uroguanylin was then found to bind to proteins on nerve cells known as GUCY2C receptors, triggering a cascade of events that led to decreased food intake.

The uroguanylin-GUCY2C endocrine axis may provide a therapeutic target to control appetite, obesity, and metabolic syndrome.

Mayo Clinic studies how much practice makes perfect when performing colonoscopies

Mon, 09 May 2011 04:00:00 PST

( from http://www.rxpgnews.com ) ROCHESTER, Minn. - A colonoscopy is an invaluable procedure for detecting problems in the colon and rectum. Doctors can often diagnose gastrointestinal issues and even catch the warning signs of colorectal cancer. Perfecting the skills required for this delicate procedure takes practice. But just how much practice makes perfect?

That was the question Robert E. Sedlack, M.D., and his Mayo Clinic research team set out to answer in their recently completed study of colorectal procedures. Their findings suggest much more practice is needed than gastroenterological professional societies currently recommend.

Current recommendations are that 140 procedures should be done before attempting to assess competency, but with no set recommendations on how to assess it, says Dr. Sedlack. Our findings suggest that it takes an average of 275 procedures for a gastroenterology fellow to reach minimal cognitive and motor competency.

The study assessed the performance of 41 Mayo Clinic Gastroenterology Fellows who performed more than 6,600 colonoscopies in Rochester, Minn., from July 2007 through June 2010. The research team used a validated testing method called the Mayo Colonoscopy Skills Assessment Tool (MCSAT).

The MCSAT is the first such tool for providing detailed assessment of the core cognitive and motor skills of trainees in this procedure, Dr. Sedlack says. As a result of our use of this test, we have been able to define learning curves and minimal competency benchmarks to identify when trainees are ready to operate independently.

The MCSAT assesses areas such as intubation rates and timing, how safely and painlessly practitioners perform the procedure and how clearly they recognize potential patient issues.

The study's findings may have particular significance for specialties other than gastroenterology. While gastroenterology fellows may perform well more than 400 colonoscopies during their training, specialists in other areas, such as surgery or family practice, may perform significantly fewer procedures during their training.

As a result of this study, and others, the American Society for Gastrointestinal Endoscopy is rewriting its colonoscopy training guidelines to reflect the need for more procedures and emphasize the use of objective, measurable tests in assessing the competency of trainees. Ultimately, these changes are good for patients. In order to ensure patient safety and provide the highest quality of care, all physicians seeking to be privileged in colonoscopy - regardless of their specialty - should be held to a common standard of competency metrics, Dr. Sedlack says.

Dr. Sedlack will be sharing the findings of this study at the 2011 Digestive Disease Week conference, to be held May 7-10 at McCormick Place in Chicago.

Attacking bowel cancer on 2 fronts

Wed, 30 Mar 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Stem cells in the intestine, which when they mutate can lead to bowel cancers, might also be grown into transplant tissues to combat the effects of those same cancers, the UK National Stem Cell Network (UKNSCN) annual science meeting will hear today.

Professor Nick Barker of the Institute of Medical Biology in Singapore will explain how he and his team identified that the stem cells which are crucial to maintaining a healthy intestine are also the site at which bowel cancers first begin, and how he also hopes to use healthy stem cells to regenerate tissues to help patients with Crohn's disease and some cancers.

Having discovered a gene that is only turned on in these particular stem cells Professor Barker and his team have been able to isolate the cells in mice and grow small pieces of intestine in the lab. The researchers hope that if they are able to grow larger pieces, they will be able to produce transplant tissues to replace damaged intestines.

Professor Barker explains: Processing our dinner every day is a tough job so the lining of our intestines quickly get worn out. To keep the intestine working stem cells in little pockets along the surface replace the lining, cell by cell, about once a week.

We already knew these stem cells existed for a while we didn't know much about them because it was difficult to distinguish them from all of the other types of cells in our intestines. Our team was able to single them out and study them because we discovered a gene that is only turned on in these particular stem cells.

Once the researchers had found this gene they were able to track where the stem cells occur throughout the body finding that, as well as the intestine, the stomach lining and in hair follicles, the cells were also present in bowel tumours.

Professor Barker continues: We hope that studying these stem cells will be doubly useful: One day we hope to grow large enough pieces in the lab to form replacement tissues for transplant; and by studying the cells we will be able to find new ways to prevent them from mutating and hence leading to cancer.

Bowel cancer is the third most common type of cancer in England and an estimated 38,000 new cases are diagnosed each year. We know these stem cells are both implicated in causing the cancer but that they also could be useful for treating disease so we hope that studying them will help us to understand how to attack the disease on two fronts.

New gene sites affecting nonalcoholic fatty liver disease discovered

Thu, 10 Mar 2011 05:00:00 PST

( from http://www.rxpgnews.com ) NAFLD is a condition where fat accumulates in the liver (steatosis) and can lead to liver inflammation (nonalcoholic steatohepatitis or NASH) and permanent liver damage (fibrosis/cirrhosis). NAFLD affects anywhere from 11% to 45% of some populations and is associated with obesity, hypertension, and problems regulating serum lipids or glucose.

These findings will help us to better diagnose, manage, and treat NAFLD in the future and help explain why some but not all people with obesity develop particular complications of obesity; some carry genetic variants that predispose them to some but not other metabolic diseases. says lead author Elizabeth K. Speliotes, M.D., Ph.D., M.P.H., an Assistant Professor of Gastroenterology, Internal Medicine, and Computational Medicine and Bioinformatics at the University of Michigan.

Investigators from The Old Order Amish, Age Gene-Environment Susceptibility - Reykjavik Study , Family Heart Study, and Framingham Heart Study, collectively called the GOLD (Genetics of Obesity-related Liver Disease) Consortium meta-analyzed genome wide association data for liver steatosis from 7,126 individuals and then followed up top associating variants in cases of NASH/fibrosis from the NASH-Clinical Research Network that were genetically matched to controls from the MIGen study to find the five variants that reproducibly associate with NAFLD. All the genetic variants found increased fat deposition in the liver. However, only some affected development of inflammation/permanent damage of the liver or development of serum lipid/glucose abnormalities.

Ingrid Borecki, Ph.D., M.S., Associate Professor of Biostatistics and Genetics, co-director of the Division of Statistical Genomics at Washington University School of Medicine in Saint Louis, and senior author on the paper says We found that approximately one quarter of the variation in NAFLD is influenced by genetic factors, and the loci we identified in the study account for about 20 percent of that genetic component. Thus the effects of these variants on NAFLD are substantial and possibly could be incorporated into clinical algorithms in the future to better classify people into risk categories. This work comes at a time when the number of people affected by these liver abnormalities is increasing, along with the prevalence of obesity in our population. Thus it is a growing problem.

Interestingly, the pattern of effects on multiple metabolic traits at two associated loci were identical and the genes closest to the best association signal at these loci are predicted to play a role in subsequent steps in triglyceride breakdown. Triglycerides are the major form of fat stored in the liver in NAFLD. This suggests that defects in triglyceride breakdown may contribute to development of NAFLD.

Through the approaches we undertook in this study we show that we can classify genes into groups, implicating new pathways, not just genes, that affect this disease. This approach can be used to identify pathways that affect other traits as well Speliotes says.

Speliotes notes that identifying variants and ultimately genes that affect NAFLD opens up new avenues for developing novel therapeutics for this condition. Currently, only weight loss and possibly increased physical activity can decrease hepatic steatosis. Getting people to lose weight and increase their physical activity however is a challenge worldwide, which is why obesity has become a global epidemic. This study provides possible new drug targets for therapeutic intervention of NAFLD. Further, our comprehensive examination of the effects of these genetic variants on multiple traits can help guide development of therapeutics against the gene targets of these variants so that we can chose targets that have specific effects on a desired disease while minimizing unwanted side effects.

New vaccine technology protects mice from hepatitis C virus

Wed, 23 Feb 2011 05:00:00 PST

( from http://www.rxpgnews.com ) Immunology: Three percent of the world's population is currently infected by hepatitis C. The virus hides in the liver and can cause cirrhosis and liver cancer, and it's the most frequent cause of liver transplants in Denmark. Since the virus mutates strongly, we have no traditional vaccine, but researchers at the University of Copenhagen are now the first to succeed in developing a vaccine, which provides future hope for medical protection from this type of hepatitis.

The hepatitis C virus (HCV) has the same infection pathways as HIV, says Jan Pravsgaard Christensen, Associate Professor of Infection Immunology at the Faculty of Health Sciences, University of Copenhagen.

Approximately one newly infected patient in five has an immune system capable of defeating an acute HCV infection in the first six months. But most cases do not present any symptoms at all and the virus becomes a chronic infection of the liver.

Poorly treated donor blood and dirty needles are sinners

Every year three or four million more people become infected and the most frequent path of infection is needle sharing among drug addicts or tattoo artists with poor hygiene, such as tribal tattoo artists in Africa and Asia. Fifteen percent of new infections are sexually transmitted, while ten percent come from unscreened blood transfusions.

According to Allan Randrup Thomsen, Professor of Experimental Virology, Egypt is one country with a high incidence of HCV. This is particularly due to lack of caution in the past with regards to screening donated blood for the presence of this virus, he says.

China, Brazil, South East Asia and African states south of the Sahara also have a high incidence, while the disease is also spreading through Eastern Europe, especially Romania and Moldova.

HCV mutates too fast for traditional vaccines

The new vaccine technology was developed by Peter J. Holst, a former PhD student now a postdoc with the Experimental Virology group, which also includes Professor Allan Randrup Thomsen and Associate Professor Jan Pravsgaard Christensen.

The technology works by stimulating and accelerating the immune system, and showing the body's defence mechanisms of the parts of the virus that are more conserved and do not mutate as fast and as often, such as the molecules on the surface of the HCV.

Basically, traditional vaccines work by showing the immune defences an identikit image of the virus for which protection is desired. Antibodies then patrol all entrances with a copy of this image and are able to respond rapidly if the virus attempts to penetrate. But the influenza virus mutates its surface molecules and in the course of a single season it takes on a new guise so that it no longer resembles the original identikit image and the vaccine loses its efficacy.

Professor Randrup explains, Mutations of the surface are Darwin at work, so to speak. The virus tries to outwit the immune defences and if it succeeds we get ill, and our response is new vaccines.

Associate Professor Pravsgaard Christensen says, Viruses like HCV mutate so rapidly that classical vaccine technology hasn't a chance of keeping up. But the molecules inside the virus do not mutate that rapidly, because the survival of the virus does not depend on it.

New vaccine technology gives immune system information about virus' stable parts

According to Professor Randrup, the body's natural defences usually don't see these internal virus molecules until the virus has taken residence in the body.

Our cells constantly show random samples of their contents to the immune defence patrols, and if there are enough foreign bodies among them, the alarm is triggered, says Professor Randrup.

The cells display fragments of the surface molecules and internal genes from the virus, and if you show the immune defences a kind of X-ray of the inner genes, they will respond. Actually, the response is extremely potent, and one of the things it does is summon the specialised CD8 killer cells.

We took a dead common cold virus, an adenovirus that is completely harmless and which many of us have met in childhood, Associate Professor Pravsgaard Christensen explains.

We hid the gene for one of the HCV's internal molecules inside it. At the same time we attached a special molecule on the internal molecule so that when the cells of the mouse body tried to take a sample, they would extract a more extensive section. The immune defences would then be presented with a larger section of the molecule concerned. You may say that the immune defences were given an entire palm print of the internal genes instead of just a single fingerprint.

This strategy resulted in two discoveries from the team. Firstly, the mice were vaccinated for HCV in a way that meant that protection was independent of variations in the surface molecules of the virus. Secondly, the immune defences of the mice saw such an extensive section of the internal molecule that even though some aspects of it changed, there were still a couple of impressions the immune defences could recognise and respond to.

The new technology to be tested in monkeys

Another virus that mutates its surface molecules with extreme rapidity is HIV. It changes skin in the space of 24 hours, and like HCV, we do not yet have a cure or a vaccine. The researchers think that HIV originally migrated to man from monkeys in the 1930s, when it was the simian Immunodeficiency virus that still circulates among a number of species of wild African monkeys.

The Danish Medical Research Council (DMRC) has given postdoc Peter Holst a grant to test our technology for a SIV vaccine for macaque monkeys in the US, says Associate Professor Pravsgaard Christensen.

The University of Copenhagen is also currently negotiating the sale of the patent for the process so that the technology can be developed for use in human vaccines.

The discovery of an effective HCV vaccine has just been published in the

Y-90 radioembolization offers promise for late-stage liver cancer

Tue, 14 Dec 2010 05:00:00 PST

( from http://www.rxpgnews.com ) INDIANAPOLIS -- The latest weapon against inoperable liver cancer is so tiny that it takes millions of them per treatment, but according to interventional radiologists at the Indiana University School of Medicine, those microscopic spheres really pack a therapeutic punch.

The glass spheres contain a radioactive element, yttrium-90, more commonly known as Y-90, which emits radiation for a very limited distance so that healthy tissue around the tumor remains unaffected. (2.5mm or less than 1/16th inch in soft tissue).

Y-90 microsphere radioembolization is an FDA-approved procedure first used in the United States in 2002. The outpatient procedure has gained favor with interventional radiologists for treating a type of cancer that is becoming more prevalent due to an increase in the cases of hepatitis and obesity, which along with alcoholism are the three primary causes of liver cancer.

Daniel E. Wertman Jr., M.D., co-director of vascular and interventional radiology and assistant professor of clinical radiology at the Indiana University School of Medicine, said more than 300 patients have been treated with Y-90 radioembolization since the program was initiated at Indiana University Hospital and the Indiana University Melvin and Bren Simon Cancer Center more than 3 years ago.

I'm really excited about the treatment, said Dr. Wertman. I think it's probably the best thing that has happened in our specialty.

His colleague, Matthew S. Johnson, M.D., professor of radiology and surgery at IU, reports very positive results with critically ill patients undergoing the treatment. Forty percent of his patients treated with radioembolization had tumors shrink or remain stable at three months. This is exceptional news since patients with advanced liver cancer have few options, he explained.

I am not aiming for a cure, I'm aiming to extend their lives and make them feel better, said Dr. Johnson.

Physicians agree that liver cancer is a very complex disease. With the Y-90 radioembolization, the disease can be address with a minimally invasive treatment and through a little band-aid sized incision we can solve very complicated problems, said Dr. Wertman.

A catheter is inserted through a tiny incision in the groin and threaded through the arteries until it reaches the hepatic artery, one of two blood vessels feeding the liver.

The physiology of the liver makes it an ideal organ for this type of treatment. The hepatic artery is the one that most commonly supplies blood to the cancerous tumors.

When the catheter is in the proper place, millions of the microscopic beads containing Y-90 are released. The microspheres lodge in the smaller vessels that directly feed the tumor, stopping blood flow and emitting radiation to kill the tumor cells.

Patients need not be isolated after treatment with Y-90 and usually are released about three hours after the treatment.

What Y-90 offers, Dr. Johnson said, is optimism. Hope is a magical thing.

Gastric bypass alters sweet taste function

Tue, 02 Nov 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Gastric bypass surgery decreases the preference for sweet-tasting substances in obese rats, a study finding that could help in developing safer treatments for the morbidly obese, according to Penn State College of Medicine researchers.

Roux-en-Y gastric bypass surgery is the most common effective treatment for morbid obesity, said Andras Hajnal, M.D., Ph.D., associate professor, Department of Neural and Behavioral Science and Surgery. Many patients report altered taste preferences after having the procedure.

This surgery involves the creation of a small gastric pouch and bypassing a portion of the upper small intestine. Unlike other weight-reduction methods, it produces substantial and durable weight loss and significant improvements in obesity-related medical conditions including diabetes.

Study results in obese rats suggest that post-surgery changes in the gastrointestinal anatomy affect change in the brain that relate to taste.

Obese rats given gastric bypass surgery showed a reduced preference for high concentration sucrose water when compared to obese rats that did not have surgery. Researchers observed a similar decrease in preference with other sweet-tasting substances, but not for salty, sour or bitter substances. Researchers observed no change in preference in lean rats that had gastric bypass surgery.

The obese rats used do not have the ability to produce the receptor for feeling satiated shortly after a meal because they lack the gut hormone CCK-1. As a result, these rats consumed larger meals and, over time, became obese and developed type-2 diabetes. Interestingly, previous studies lead by the Penn State investigators found an increased sweet preference in these rats, which is also often seen in people struggling with weight management.

It appears that an uncontrolled appetite may get further boost from altered taste functions during development of obesity and diabetes, Hajnal said. How much of this vicious circle is due to changes in the neurons inside the brain, which receive taste sensations from the tongue and report to the higher order motivational brain centers, we don't know.

The researchers recorded the activity of 170 taste-responsive neurons in the brain. These showed a shift in the neurons' firing activity similar to the behavioral response, which was measured in lick rates of the rats within a ten-second time period. Neurons in the obese rats' brain responded more vigorously to higher-concentration sucrose water placed on the tongue when compared to lean rats. These effects were reversed by gastric bypass surgery and matched the response of lean rats -- a preference for lower concentration sucrose.

The rats that had gastric bypass surgery lost weight comparable to humans who received the surgery -- 26 to 30 percent of their weight -- and maintained the loss for a long period of time after surgery. Following surgery, the obese rats also showed a higher tolerance for glucose, indicating improvement in diabetes.

This supports the applicability of this rat model of Roux-en-Y gastric bypass to humans and also suggests that the observed taste changes following the surgery were not related to 'human factors' such as awareness and compliance to dietary and behavioral interventions, Hajnal said.

The researchers published their findings in the October issue of the

Liver hormone is a cause of insulin resistance

Tue, 02 Nov 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers have identified a hormone produced and secreted by the liver as a previously unknown cause of insulin resistance. The findings, in the November issue of Cell Metabolism, a Cell Press publication, suggest a new target for the treatment of insulin resistance and type 2 diabetes, the researchers say.

The current study sheds light on a previously underexplored function of the liver; the liver participates in the pathogenesis of insulin resistance through hormone secretion, said Hirofumi Misu of Kanazawa University Graduate School of Medical Science in Japan.

The researchers had discovered earlier that genes encoding secretory proteins are abundantly expressed in the livers of people with type 2 diabetes. On the basis of those findings, Misu and colleagues began to suspect that, similar to the role of fat tissue, the liver might contribute to the development of type 2 diabetes and insulin resistance via secretory proteins they call hepatokines.

Now, the researchers report the results of comprehensive gene expression analyses, revealing that the liver expresses higher levels of the gene encoding selenoprotein P (SeP) in people with type 2 diabetes who are more insulin resistant. Blood levels of SeP are also increased in people with diabetes compared to healthy people.

Further studies in mice added support to the notion that the connection between SeP and insulin resistance is causal. When the researchers gave normal mice SeP, they became insulin resistant and their blood sugar levels rose. A treatment that blocked the activity of SeP in the livers of diabetic and obese mice improved their sensitivity to insulin and lowered blood sugar levels.

Misu said that SeP was known previously as a protein produced mainly in the liver, where it transports the essential trace element selenium from the liver to other parts of the body. But the protein's clinical significance and, more specifically, its role in glucose homeostasis weren't known.

In the development of insulin resistance, the researchers don't think SeP acts on its own. It is well known, they explain, that fat tissue is a main contributor to the development of insulin resistance by producing fat-derived hormones called adipokines. But they say they have preliminary evidence for a connection between SeP and adipokine production, which will be the subject of further investigation.

The new findings suggest that there may be other hormones derived from the liver with important and varied roles in the body, Misu and his colleague Toshinari Takamura add. Our study raises the possibility that the liver functions as an endocrine organ by producing a variety of hepatokines and that the dysregulation or impairment of hepatokine production might contribute to the development of various diseases.

Increased mortality risk in later years in obese children following Liver transplantation

Thu, 28 Oct 2010 18:27:35 PST

( from http://www.rxpgnews.com ) A new study from the University of Washington reported obese children are at increased mortality risk in later years following primary liver transplantation (LT). Pediatric patients who are thin or severely thin, experience an early mortality risk—within the first year post-LT. Details of the ten-year survival analysis are published in the November issue of Liver Transplantation, a peer-reviewed journal of the American Association for the Study of Liver Diseases (AASLD).

Childhood obesity is a serious public health concern worldwide. According to the World Health Organization (WHO), the prevalence of obesity has been increasing at an alarming rate, with 22 million children under the age of five worldwide who are overweight. In the U.S., the National Center for Health Statistics estimates that 17% of children between the ages of 2 and 19 years old are overweight or obese.

"Controversies exist regarding the mortality of patients undergoing liver transplantation at the extremes of body mass index (BMI), and in pediatric patients weight is typically the only factor considered in survival analysis," explained lead study author André Dick, M.D., from Seattle Children's Hospital and the University of Washington. "Our study is the largest thus far to report on the impact of pre-transplant BMI on post liver transplant survival in the pediatric population." Prior studies in adult populations have shown there to be a negative impact on post transplantation survival for LT patients with extreme BMIs.

For the present study, researchers reviewed data from the Organ Procurement and Transplantation Network (OPTN) and found that 7,942 patients less than 18 years of age (who had full BMI data) underwent primary liver transplantation between 1987 and 2007. Using the WHO BMI criteria, the authors categorized patients as severely thin, thin, normal weight, overweight, or obese. During the study period 61% of patients were at normal weight.

Results indicate that children who were thin or severely thin had a significantly lower survival (84%) at one year compared to the survival (89%) of children in the normal and overweight groups. Researchers found no significant difference in survival during the first year after transplantation for obese pediatric patients. However, by the twelfth year following LT, those in the obese group had significantly lower survival (72%) than the survival (77%) of normal weight or overweight pediatric patients.

The authors observed that obesity had a significantly negative impact on pediatric patient survival more than five years after LT. They speculate post metabolic syndrome (PTMS) could contribute to the late morbidity and mortality due to the time it takes to develop long-term obesity-related conditions such as diabetes, hypertension, and hyperlipidemia. Moreover, long-term use of immunosuppressive therapy following transplantation, which while improving patient survival, can exacerbate the effects of PTMS. "Further research is needed to determine the optimal immunosuppressive regimen that will lessen the effects of PTMS," concluded Dr. Dick. "Pre- and post-transplant identification of malnourished or obese pediatric patients, along with optimization of their modifiable risk factors will help to best use scarce donor organs and maximize patient survival."

NC Children's Hospital part of $12 million grant to create first-of-kind registry for IBD

Wed, 13 Oct 2010 04:00:00 PST

( from http://www.rxpgnews.com ) CHAPEL HILL, N.C. -- Building on the success of previous efforts among researchers and caregivers to improve the care of chronically ill children, North Carolina Children's Hospital is one of 27 sites across the nation developing a disease registry for inflammatory bowel diseases (IBD). The research collaborative is part of a $12-million grant to Cincinnati Children's Hospital Medical Center, enabling the creation of this first-of-its-kind registry system providing real time information on thousands of IBD cases across the country and, eventually, around the world.

This extraordinary collaboration will make available electronic medical record data about symptoms, treatments and outcomes for patients at multiple locations throughout the United States. It will allow doctors and researchers to assess which treatment strategies are having the greatest positive impacts on patients.

Although patients with any chronic illness could eventually benefit from this work, the grant is focused on enhancing an already-successful collaborative network (ImproveCareNow) focused on inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, conditions that affects around 100,000 children in the United States. The University of North Carolina Chapel Hill is one of the founding centers in the ImproveCareNow collaborative.

I am particularly excited to be working with this national, multidisciplinary team of investigators on this innovative and ambitious project, said Michael Kappelman, MD, MPH, an assistant professor of pediatrics at the UNC School of Medicine. This grant has made possible the IT infrastructure necessary to pool electronic clinical data from multiple hospitals and practices in order to promote continuous quality improvement work and simultaneously learn more about the real world effectiveness of the multiple treatment options for patients with this condition.

Kappelman is a pediatric gastroenterologist, digestive disease epidemiologist, and health services researcher at UNC Chapel Hill with both clinical and research expertise in pediatric IBD. He has been the chair of the ImproveCareNow research committee for three years and has been newly named the collaborative's director of data management. Kappelman and Darren DeWalt, MD, MPH, from the division of general internal medicine, are co-investigators on this grant.

The grant was awarded by the federal Agency for Healthcare Research and Quality, which supports research that leads to more informed decisions and improves the quality of health care services. This grant builds on the research from last year's $8 million transformative research grant from the National Institutes of Health to create a network of patients, clinicians and researchers to improve management of chronic care.

Rather than waiting months or years for peer-reviewed papers to be published on outcomes involving a relatively small number of patients, the new registry will allow information to flow directly from patients' electronic medical records into the database, creating a real-time body of shared knowledge that can be accessed and reviewed immediately, making best practices and corresponding outcomes available to clinicians, researchers, hospitals, clinics, administrators, policymakers, and even patients themselves.

The principle investigator for the project, John Hutton, MD, director of Biomedical Informatics at Cincinnati Children's, expects the registry to come on-line in stages over the next three years.

IBD is a relatively uncommon condition so no center has enough patients to determine the best care practices, said Hutton. The registry will make the latest and most up-to-date information about treatment and outcomes available to everyone. Our hope is that this project will demonstrate this is a dynamic, effective way to identify the most successful treatment options and get them into broader practice much faster.

The registry is the next step in what has been a successful effort over the past four years among caregivers and researchers who have been sharing information on IBD through the ImproveCareNow network of physicians. By sharing information and comparing notes, doctors have been able to improve remission rates for patients with IBD by as much as 20 percentage points over just the past three years. As of June 30, 71 percent of the patients cared for by the collaborative were in remission.

In addition to the University of North Carolina Chapel Hill, the grant proposal was also prepared by investigators at the University of Vermont (where ImproveCareNow is based), Cincinnati Children's Hospital Medical Center, Children's Hospital of Philadelphia, The Children's Hospital in Denver, Nationwide Children's Hospital in Columbus, and Nemours Children's Clinics in Delaware. In all, nearly 30 different sites taking care of thousands of patients are part of the collaborative network. (A list of the sites is included at the end of the release.)

It is estimated that about 1 million people in the United States have Crohn's disease and ulcerative colitis, and 10 percent of them or 100,000 are children under the age of 18. Children with these diseases often suffer from abdominal pain, diarrhea, bloody stools, poor appetite, weight loss and poor growth, and must struggle to lead active lives. The diseases are due to a chronic inflammation of the intestinal tract.

Locations of GI practices included in this chronic care collaborative include:

NYU Langone Medical Center receives NIH Director's Transformative Research Projects award

Thu, 30 Sep 2010 04:00:00 PST

( from http://www.rxpgnews.com ) The National Institutes of Health (NIH) announced today that Martin J. Blaser, MD, the Frederick H. King Professor of Internal Medicine at NYU Langone Medical Center has been awarded one of only twenty NIH Director's Transformative Research Projects (T-R01) award for research entitled Disappearing Gastrointestinal Microbiota in Epidemic Obesity. The project will examine whether changes in the human microbiome as a result of antibiotic use early in life has fueled the epidemic of obesity. The amount of the award is approximately $6.6 million over a five year period.

We are deeply committed to the mandate of translational research and will use the opportunity to try to prevent and treat obesity which has become a global epidemic, says Vivian S. Lee, MD, PhD, MBA, senior vice president, vice dean for science and chief scientific officer at NYU Langone Medical Center. We are excited that collaborations between multiple departments at the medical center may result in research that could be transformative and far-reaching.

Currently, over 1/3 of U.S. adults are obese and one of six children are overweight. In fact, rates of obesity have increased so rapidly over the past three decades that scientists believe that there must be an environmental cause. Dr. Blaser and colleagues hypothesize that antibiotic use early in life has resulted in the disappearance, or extinction, of key microbiota in the human gastrointestinal tract.

Antibiotic use in children may have resulted in the gradual disappearance of Helicobacter pylori, the ancient stomach bacteria that interact with hormones, to maintain energy homeostasis. Dr. Blaser has also observed that use of low dose antibiotics in farm animals to promote growth may also have had a parallel result in human children repeatedly exposed to high-dose antibiotic doses at a very young age. He hypothesizes that antibiotic use could be disrupting metabolic relationships that control early life development.

The human microbiome has been selected, and passed from mother to child, because the bacterial genes are helpful, says Dr. Blaser who is also a professor of Microbiology at NYU Langone Medical Center. But as a result of modern practices including widespread antibiotics use, caesarean sections, amalgam dental fillings, constant cleansing, clean water, smaller families and transmission of these normal ancestral microbes has changed, and there are consequences. Some consequences might be good, while others could be bad.

Dr. Blaser and his colleagues at NYU Langone Medical Center have been studying microbes for over thirty years. Microbal cells, collectively known as the human microbiome, reside on our skin and inside our bodies, outnumbering the cells of our own bodies by 10 to 1. They communicate with our own cells and with our immune system, carry out essential metabolic tasks, crowd out pathogens, degrade toxins, and help digest our food.

Advances in DNA sequencing technologies have allowed for further investigation of microbes. Through the Human Microbiome Project (HMP), over 900 species of microbes have been genetically sequenced in an effort to determine the ways changes in the microbiome correlate with human health and disease. The T-R01 grant will help further the understanding of metabolic effects of antibiotic use on normal microbiome development.

Right now, antibiotics are used in children early in life to treat ear infections and other ailments, and the thought process is that it may not 'help', but it certainly doesn't 'hurt,' says Dr. Blaser. But what if antibiotic use actually 'hurts?' What if there are unintended consequences of the 'use' or 'overuse' of antibiotics? This is the question we hope to answer.

The grant will involve multiple departments at NYU Langone Medical Center, including the Departments of Medicine, Pathology Radiology, Obstetrics and Gynecology, Environmental Medicine, and Microbiology and support multiple studies:

Unique gastroenterology procedure developed in adults shows promise in pediatrics

Mon, 27 Sep 2010 04:00:00 PST

( from http://www.rxpgnews.com ) The use of device-assisted enteroscopy, a technique that allows complete examination of the small bowel, may be just as successful pediatrics as it has been in adult medicine, according to a study from Nationwide Children's Hospital.

One of these techniques known as Double-Balloon Enteroscopy (DBE), a procedure readily available in adults, allows doctors to reach parts of the small intestine that cannot be reached using standard endoscopic procedures. Due to access issues and size limitations, DBE is rarely considered an option in pediatrics. As a result, little is known about this technique in children.

Since the introduction of fiberoptic endoscopy in the 1950s, gastrointestinal endoscopy has undergone dramatic progress in how it can aid in the diagnosis and treatment of patients, said Steven H. Erdman, MD, gastroenterologist and at Nationwide Children's Hospital and one of the study authors.

Yet, even with this progress, endoscopic examination and treatment in the small intestine has remained a challenge, especially in children. Small intestinal enteroscopy in the pediatric population remains relatively unknown and underutilized, said Dr. Erdman, also a professor of Clinical Pediatrics at The Ohio State University College of Medicine.

To shed light on the indications and possible benefits of DBE in children, physicians from Nationwide Children's reviewed the outcomes of DBE cases performed at the hospital during a two-year period. The physicians performed a total of 13 DBE procedures on 11 pediatric and adolescent patients. Prior to the DBE, all patients underwent a detailed diagnostic evaluation including laboratory testing and diagnostic radiologic imaging along with upper endoscopy, colonoscopy and capsule endoscopy (CE) tests. Abnormal small intestinal CE findings or continued small bowel disease symptoms without diagnosis by conventional methods were used as indications for DBE.

Two of the patients underwent DBE for treatment of small intestinal polyps associated with Peutz-Jeghers Syndrome which dramatically improved their symptoms of abdominal pain and bleeding. Another patient's DBE was done to remove a bleeding small intestinal vascular malformation that had caused years of symptoms resolving chronic anemia. Two other patients had histories of bloody diarrhea, anorexia and weight loss; lower DBE provided evidence leading to the diagnosis of Crohn's disease when other medical techniques had been unsuccessful.

DBE can be associated with abdominal discomfort following the procedure due to gaseous distention as was seen in five of the 13 procedures. Utilizing carbon dioxide rather than regular air to fill the intestine during this procedure has eliminated this issue.

Noting the limitations of this study on a small number of patients from a single institution, Dr. Erdman says that DBE appears to hold promise for pediatrics. Our experience suggests that DBE shows great potential in the diagnosis and management of pediatric small intestinal disease without undue risk, he said. Since completion of the original report, eight additional DBE procedures have been completed with similar positive outcomes.

Although DBE shows great potential, Dr. Erdman warns that pediatric centers may not be able to devote the necessary resources and time needed to provide this type of service. DBE remains a resource-intensive procedure requiring multiple staff, general anesthesia and extended procedure time in addition to cost outlays for equipment, he said. These instruments were designed for use in adults and size is a limitation that remains to be address before DBE can become a more standardized tool in pediatric gastroenterology.

Proof that a gut-wrenching complaint -- irritable bowel syndrome -- is not in your head

Thu, 19 Aug 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Irritable bowel syndrome makes life miserable for those affected -- an estimated ten percent or more of the population. And what irritates many of them even more is that they often are labeled as hypochondriacs, since physical causes for irritable bowel syndrome have never been identified. Now, biologists at the Technische Universitaet Muenchen (TUM) have shed new light on the matter: They have discovered mini-inflammations in the mucosa of the gut, which upset the sensitive balance of the bowel and are accompanied by sensitization of the enteric nervous system.

Flatulence, constipation and diarrhea, nausea and stomach cramps: Irritable bowel syndrome (IBS) can turn digestion into a nightmare. Frequent visits to the bathroom are often accompanied by sleep disturbances, headaches, and backaches. In Germany alone, some seven million people are affected by the disorder -- and by the fact that their irritable bowel syndrome is often deemed psychosomatic. This is because the organic trigger of the disease has never been discovered, and consequently the various therapeutic interventions are disappointing for both the patients and their doctors. That may soon change, however, because now, for the first time, biologists in Munich have nailed down hidden physical causes of this bowel disorder.

Professor Michael Schemann's research team at the TUM Department for Human Biology has managed to demonstrate that micro-inflammations of the mucosa cause sensitization of the enteric nervous system, thereby causing irritable bowel syndrome. Using ultrafast optical measuring methods, the researchers were able to demonstrate that mediators from mast cells and enterochromaffin cells directly activate the nerve cells in the bowel. This hypersensitivity of the enteric nervous system upsets communication between the gut's mucosa and its nervous system, as project leader Prof. Schemann explains: The irritated mucosa releases increased amounts of neuroactive substances such as serotonin, histamine and protease. This cocktail produced by the body could be the real cause of the unpleasant IBS complaints.

The TUM researchers in human biology are blazing a trail as they follow this lead. Their current focus is to what extent nerve sensitization correlates with the severity of symptoms. Working with colleagues from Amsterdam, they have already substantiated the clinical relevance of their results: Irritable bowel symptoms improved after treatment with an antihistamine known for its immune-stabilizing effect in the treatment of allergic reactions such as hay fever. Thanks to funding from the German Research Foundation (DFG), the scientists are now investigating whether the improved symptoms are accompanied by a normalization of nerve activity.

Successful identification of the active components could enable the development of effective drugs to treat irritable bowel syndrome. Even now, though, the TUM team have made life easier for many IBS patients, in that they have shown that the chronic disorder does have physical causes and is not merely in their heads.

Some patients with hepatitis B faring better after liver transplant

Tue, 04 May 2010 04:00:00 PST

( from http://www.rxpgnews.com ) ROCHESTER, Minn. -- Treatment to reduce recurrence of hepatitis B appears to improve liver transplant outcomes for some patients, according to a Mayo Clinic study presented at the American Transplant Congress under way May 1-5 in San Diego.

We found that in patients with hepatitis B, the number of patients who were listed for a second transplant within three years decreased by 50 percent between 1996 and 2005, says Ray Kim, M.D., the senior investigator of the research team.

Hepatitis B infection is a major cause of liver damage that can eventually lead to end-stage liver disease and the need for a liver transplant. In the past, hepatitis B recurred in some transplant patients, causing liver damage and the need for a second transplant.

In the past 10 years, new medications have improved our ability to control hepatitis B, says Dr. Kim. Today, transplant recipients routinely are treated with antiviral therapy and hepatitis B immune globulin to reduce the risk of recurrence. We wanted to know if the medication protocols were making a difference in patient outcomes, he says.

Researchers reviewed data provided by the Organ Procurement and Transplantation Network of 31,242 liver transplants in the United States. The underlying reasons for transplantation were categorized as hepatitis B, hepatitis C or other.

From 1996 to 1998, 6.5 percent of liver transplant patients with hepatitis B were listed for a second transplant. For 2003 to 2005, the number of liver transplant patients with hepatitis B listed for a second transplant was 3.3 percent -- roughly a 50 percent reduction.

For patients with hepatitis C or other underlying liver disease, there were smaller declines in relisting numbers. Preventing recurrence of hepatitis C has proved to be more challenging than preventing recurrence of hepatitis B, says Dr. Kim.

Over the same periods, mortality rates increased for all three groups. For patients with hepatitis B, the death rate was 10.8 percent from 1996 to 1998. The rate increased to 12.8 percent for 2003 to 2005.

Our results show that transplant outcome is consistently improving for patients with hepatitis B with a significant decrease in need for second transplants, says Dr. Kim. The increases in mortality rates are concerning. The incidence of liver cancer has increased and it may explain some of the mortality. However, more work needs to be done to understand the reasons.

Dr. Kim says the study results are significant because an estimated 800,000 Americans have hepatitis B. That number is likely an under-representation, he says. In some U.S. immigrant communities, which often are excluded in disease tracking national surveys, the hepatitis B infection rate is 5 to 15 percent.

Those high numbers portend a continued high demand for liver transplants. In the United States, nearly 16,000 people are waiting for liver transplants.

Study shows liver transplant center impacts patient outcomes

Sun, 02 May 2010 04:00:00 PST

( from http://www.rxpgnews.com ) ROCHESTER, Minn. -- For patients in need of a liver transplant, their choice of a transplant center can make a noteworthy difference in their outcomes, according to a Mayo Clinic study presented at the American Transplant Congress under way May 1-5 in San Diego.

We did find significant variation between centers in patient outcomes in the first year after transplant, says Ray Kim, M.D., one of the lead investigators on the study. Previous studies have looked at outcomes based on factors about the recipients and donors involved, but no known previous study has focused on what effect the transplant center could have on patient outcomes.

Researchers documented an average 30 percent difference in risk for failed transplant between centers. Between centers with the best and worst outcomes, there may be as much as a fourfold difference in risk. Failed transplant was defined as either patient death or the need for a subsequent liver transplant within a year. Though one intuitively expects a certain amount of difference between centers, this effect seems larger than previously thought. The bottom line for patients: do your homework before selecting a transplant center, he says.

But transplant center size alone, measured in patient volume, didn't account for the difference in outcomes. Results showed that the number of transplants performed didn't materially affect outcomes, says Dr. Kim. This implies the largest center won't necessarily have the best results. Similarly, a smaller center may deliver similar outcomes.

Using data from the Organ Procurement and Transplantation Network, Mayo Clinic researchers reviewed data from 12,233 patients who received liver transplants to treat chronic liver disease. The data included transplants performed at more than 100 U.S. hospitals that performed at least one liver transplantation surgery from 2005 to 2008.

Of those transplants, 15 percent failed within a year. The outcome differences between transplant centers were greatest during the first three months post-transplant.

Data used in the study was combined and analyzed without naming the transplant centers. The goal of the research is not to point fingers, says Dr. Kim. The study was undertaken with the hope of finding ways for the transplant community to make the best use of a very limited resource, namely the donated organs. The data clearly showed that where the transplantation is done makes a difference whether the outcome of a transplant will be successful. In the United States, nearly 16,000 people are waiting for liver transplants.

Dr. Kim notes that there may be several ways transplant center factors can affect transplant outcomes. The most immediate factor is quality of care provided at the center, including surgical, medical and nursing expertise. In addition, how patients and donor organs are selected for transplantation also contributes to the outcome. And last, where the center is located geographically has a substantial impact on availability and quality of donated organs.

Extracorporeal liver support therapy shows promise for severely ill patients

Sun, 18 Apr 2010 12:49:40 PST

( from http://www.rxpgnews.com ) Vienna, Austria: Results from two studies presented on 16th April 2010 at the International Liver Congress 2010 have shown that treatment with extracorporeal devices may not confer a survival advantage for severe liver failure patients, despite positive dialysis effects. However, results among a small sub-group of patients show promise.

Extracorporeal liver support therapy is in its infancy but is valued as a detoxification treatment option for patients with cirrhosis who have rapid worsening of their liver function. The objectives of these two studies were to better understand the potential of two new devices (Molecular Adsorbent Recirculating System – MARS - and Prometheus®) in terms of survival benefits for patients who suffer from cirrhosis.

Commenting on the studies, Professor Burroughs from the Royal Free Hospital NHS Trust, London UK, said: "The accepted prognosis for these patients is generally poor and current treatment strategies involve supportive therapy, with the hope that liver function will recover if sufficient time is allowed. Extracorporeal support systems such as the two included in these studies are very useful bridges, but the overall data on survival is disappointing. The positive data for severely ill patients with hepatorenal syndrome I or a MELD score over 30, though, does offer some encouragement".

In the first study , 145 patients with cirrhosis and rapid deterioration of their liver function were recruited across seven European countries. This study is the first large prospective randomized controlled trial on the survival of patients with the condition (HELIOS study). Prometheus® is a new extracorporeal liver support system allowing the removal of protein bound and water soluble toxins by fractionated plasma separation and absorption (FPSA). Patients were randomized to standard medical therapy or standard medical therapy plus FPSA and the primary endpoints of the study were survival at 28 and 90 days regardless of liver transplantation.

The results show that difference in the overall survival was not statistically different overall (66% vs. 63% p=0.7 at day 28 and 47% vs. 38% p=0.35 at day 90). Only in pre-defined patient sub-groups with hepatorenal syndrome type I* and MELD** score >30 was a significant survival benefit with treatment with FPSA observed (p=0.04 and p=0.02 respectively).

*Hepatorenal syndrome type I is a common type of rapidly progressive kidney failure that affects individuals with liver cirrhosis, with a doubling of serum creatinine to a level greater than 2.5 mg/dL or a halving of the creatinine clearance to less than 20 mL/min over a period of less than two weeks.

**The Model for End-Stage Liver Disease, or MELD, is a scoring system for assessing the severity of chronic liver disease. MELD uses the patient's values for serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time (INR) to predict survival.

In the second study , 189 patients with acute-on-chronic liver failure across six European countries were randomized either to treatment with the Molecular Adsorbent Recirculating System (MARS) or to standard therapy. Treatment with MARS was scheduled at low dose (up to ten sessions of 6-8 hours during 21 days) and the main endpoint was survival at 28 days.

Results showed a significant decrease in serum creatinine (20.0 ±33.1% vs. 6.4 ±33.5% p=0.02) and bilirubin (26.4 ±26.1% vs. 8.9 ±22.3% p=0.001) as well as higher improvement in the hepatic encephalopathy (estimated by the percentage of evaluations in which HE decreased from II-IV at inclusion to 0-I during therapy, 56% vs. 39% p=0.06) in the MARS group. The primary endpoint was not met however, with the proportion of patients dying within 28 days almost identical in both groups (40.8% vs 40.0%). Findings show that MARS at low dosage is a safe procedure which has significant dialysis effect and improves severe hepatic encephalopathy in patients with cirrhosis and rapid deterioration of their liver function; however a significant beneficial effect on survival could not be demonstrated.

Keeping the weight off after a very low-energy diet

Sun, 04 Apr 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Simple advice can reduce the risk of weight regain after a very-low-energy diet: the secret to keeping the weight off is to switch back to normal food gradually, reveals a dissertation from the Sahlgrenska Academy, at the University of Gothenburg, Sweden, which also contains new research results for patients who have undergone obesity surgery.

For 12 weeks a group of just over 260 patients swapped their normal food for a very-low-energy diet in the form of soups and milkshakes. 169 of the patients lost a lot of weight, averaging 16 per cent of their body weight. They were then divided into two groups so that they could switch back at different rates from the very-low-energy diet to energy reduced portions of normal food. One group completed the refeeding in a week, while the other took six weeks.

After ten months the patients with the six-week refeeding period had gained 4 per cent in weight from their minimum weight, while the patients with the one-week refeeding period had gained eight per cent, says Lena Gripeteg, researcher at the Sahlgrenska Academy.

Very-low-energy diets have been used for many years in the health service to achieve rapid and safe weight loss in obese patients. While this treatment method is well-studied, there is a risk that patients will gain weight when they start to eat normal food again.

We therefore want to look at the importance of different treatment advice on the transition from the very-low-energy diet back to normal food, and assess what actually works, says Gripeteg. A simple tip that seems to work for patients is to revert slowly to normal food after losing weight on a very-low-energy diet.

Her dissertation also includes research results from the current national SOS (Swedish Obese Subjects) study, which has followed 2,010 patients who have undergone surgical treatment for obesity and 2,037 matched control patients for up to 20 years. It shows that men who have undergone obesity surgery are less likely to need a disability pension, while obese women are just as likely to need a disability pension whether they lose weight or not.

On the basis of this study, we can't explain why there is a difference in the sexes, says Gripeteg. It may well be that the underlying health problems differ between women and men, which could explain why there is a significant improvement in the ability to work in men, but no effect in women after surgical obesity treatment.

Demographic profile suggests environmental role in etiology of Crohn's Disease

Sat, 06 Feb 2010 12:58:48 PST

( from http://www.rxpgnews.com ) Although inflammatory bowel disease (IBD) [comprising mainly Crohn's disease (CD) and ulcerative colitis (UC)] is thought to affect about 150 000 people in the United Kingdom, the prevalence of severe IBD is not known. Mortality following hospitalization for IBD is significant but little has been reported on long-term follow-up.

A research article to be published on January 28, 2010 in the World Journal of Gastroenterology addresses this question. The research team from United Kingdom determined the hospitalized prevalence of severe IBD and subsequent 5-year mortality in Wales, and investigated associations between severe IBD and social deprivation, distance travelled to hospital, and other socio-demographic characteristics.

They found that hospitalization for severe CD was more common among women than men and it peaked among younger people aged 16󈞉 years. UC was similar among men and women and was more common among older people. There was no link between social deprivation and UC, but CD was more common among more deprived social groups.

The differing demographic profiles between CD and UC, suggest that environmental factors play a more significant role in the etiology of CD. The findings of this large population-based study on the prevalence and mortality of IBD are also important for service planning and provision.

A novel and simple formula to predict treatment success in chronic hepatitis C

Thu, 14 Jan 2010 05:00:00 PST

( from http://www.rxpgnews.com ) The likelihood of treatment success of 48 wk peg-interferon (PEG-IFN) plus ribavirin (RBV) therapy for chronic hepatitis C may be predicted by viral kinetics on therapy. In particular, recent studies have shown that sustained virological response (SVR) can be predicted by a rapid virological response (RVR), and an early virological response (EVR). Nevertheless, the current dosing regimens could potentially under-treat some patients and additional measurements of viral response is needed to facilitate individualization of therapy. Among predictive factors already reported, many are not readily available from daily clinical assessment, because they require genomic analyses and/or advanced experimental methods. The prediction with simply available data may be useful.

A Clinical research article to be published on January 7 , 2010 in the World Journal of Gastroenterology suggested a novel but easily available on-treatment formula, which predicted SVR of patients who received PEG-IFN/RBV for 48 wk better than viral kinetics. The analysis was performed using the data of 176 patients with chronic hepatitis and hepatitis C virus genotype 1 who received 48 wk standard therapy. The formula was constructed using data from the first 100 patients enrolled and validated using data from the remaining 76 patients.

The predictive potential was very high, as judged by area under the curve of receiver operating characteristic (AUC) analysis, which was more than 0.8 from week 4. In particular, the validity at week 24 was more than 0.85 of AUC. The positive predictive value (PPV) of the formulae were better at weeks 12 and 24 than the prediction with viral kinetics, and the negative predictive value (NPV) of the formulae were better at weeks 4 and 12. Evaluation of the formulae using data from the test patients revealed a very high AUC value of more than 0.85. These results suggest that formulae based on simple clinical data are superior to prediction by viral kinetics.

The formula can be made with a personal computer using statistical software to create a logistic regression model. The formula was made for every cohort of patients affiliated to a hospital, and the prediction made is suitable for every cohort. The concept that extension of treatment duration can reduce relapse rates should be adopted only for a limited proportion of type 1-infected patients. The formulae we suggest might be helpful for patients who are expected to achieve SVR but do not do so. For those individuals, the method based on logistic regression analysis will show a clear direction of therapy in each case and enable the best tailored treatment. Further prospective studies should be performed to determine whether this approach really increases the SVR rate by selection of patients and extension of treatment duration up to week 72.

Fat in the liver -- not the belly -- is a better marker for disease risk

Mon, 24 Aug 2009 04:00:00 PST

( from http://www.rxpgnews.com ) New findings from nutrition researchers at Washington University School of Medicine in St. Louis suggest that it's not whether body fat is stored in the belly that affects metabolic risk factors for diabetes, high blood triglycerides and cardiovascular disease, but whether it collects in the liver.

Having too much liver fat is known as nonalcoholic fatty liver disease. The researchers report online in the journal PNAS Early Edition that when fat collects in the liver, people experience serious metabolic problems such as insulin resistance, which affects the body's ability to metabolize sugar. They also have increases in production of fat particles in the liver that are secreted into the bloodstream and increase the level of triglycerides.

For years, scientists have noted that where individuals carried body fat influences their metabolic and cardiovascular risk. Increased fat inside the belly, known as visceral fat, is associated with an increased risk of diabetes and heart disease.

Data from a large number of studies shows that visceral fat is associated with metabolic risk, which has led to the belief that visceral fat might even cause metabolic dysfunction, says senior investigator Samuel Klein, M.D. However, visceral fat tracks closely with liver fat. We have found that excess fat in the liver, not visceral fat, is a key marker of metabolic dysfunction. Visceral fat might simply be an innocent bystander that is associated with liver fat.

Klein, the Danforth Professor of Medicine and Nutritional Science, directs the Division of Geriatrics and Nutritional Science and the Center for Applied Research Studies, as well as Washington University's Center for Human Nutrition. He says most of our body fat, called subcutaneous fat, is located under our skin, but about 10 percent is present inside the belly, while much smaller amounts are found inside organs such as the liver and muscle.

This study compared obese people with elevated and normal amounts of liver fat. All subjects were matched by age, sex, body mass index, percent body fat and degree of obesity. Through careful evaluations of obese people with different amounts of visceral fat or liver fat, Klein's team determined that excess fat inside the liver identifies those individuals who are at risk for metabolic problems.

We don't know exactly why some fats, particularly triglycerides, will accumulate inside the liver and muscle in some people but not in others, says first author Elisa Fabbrini, M.D., Ph.D., assistant professor of medicine. But our data suggest that a protein called CD36, which controls the transport of fatty acids from the bloodstream into different tissues, is involved.

Fatty acids are the building blocks for making fats, known as triglycerides. Klein, Fabbrini and their colleagues found that CD36 levels were lower in fat tissue and higher in muscle tissue among people with elevated liver fat.

Fabbrini and Klein say changes in CD36 activity could be responsible for diverting circulating fatty acids away from fat tissue and into liver and muscle tissue, where they are converted to triglyceride. Increased tissue uptake of fatty acids could be responsible for metabolic dysfunction.

Klein says those who are obese but don't have high levels of fat in the liver should be encouraged to lose weight, but those with elevated liver fat are at particularly high risk for heart disease and diabetes. He says they need to be treated aggressively to help them lose weight because dropping pounds can make a big difference.

Fatty liver disease is completely reversible, he says. If you lose a small amount of weight, you can markedly reduce the fat content in your liver. In fact, even two days of calorie restriction can cause a large reduction in liver fat and improvement in liver insulin sensitivity.

Sequential TACE and cryosurgery can improve survival times for patients with HCC?

Tue, 11 Aug 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Hepatocellular carcinoma (HCC)--a liver cancer--is recognized as one of the most common cancers in the world that disproportionately affects Southeast Asians and Africans. While there are therapies that possibly provide a cure, surgical removal and liver transplantation are invasive and radical options. However, even these approaches only benefit a small proportion of the total number HCC patients. Cryosurgery is a minimally invasive technique of using extreme low temperatures to freeze and kill tumors, improve patient' survival times, and reduce surgical complications. Cryosurgery can be potentially applied to any surgery for solid organ cancers where conventional surgery would otherwise be used to remove undesirable tissue. It is anticipated that in the near future, cryosurgery will increasingly replace the use of traditional techniques of ablation.

A research article discussed will be published on August 7, 2009 in the World Journal of Gastroenterology. This article will address the best method to treat HCC which can not be removed by operation. The findings of this study are significant to the procedures that are performed daily at Fuda Cancer Hospital Guangzhou, and will hopefully change the practices at other cancer centers as well.

TACE is based on the fact that normal liver gets its blood supply from two sources: the portal vein (about 70%) and the hepatic artery (30%). HCC gets its blood exclusively from the hepatic artery. TACE works by sending a catheter up the hepatic artery and its branch, and then injecting embolic material. Embolization blocks the tumor-feeding vessels and leads to cancer cell death and tumor shrinkage. Without this procedure, the hepatic artery and branches would continue to feed the liver tumor and allowing it to continue growing.

TACE performed prior to cryoablation may be expected to increase the efficacy of the cryoablation for HCC, to decrease local recurrence at the ablation area, improve survival times, and reduce bleeding complications. Cryosurgery combined with TACE, allows a broader group patients with HCC to be treated. Previously, only a small portion of HCC patients could be treated with conventional methods; even then, only those with small tumors. If TACE is performed prior to cryosurgery, more patients can be treated, even those with larger tumors.

Enzyme involved in inflammatory bowel disease discovered at Penn State College of Medicine

Tue, 02 Jun 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers at Penn State College of Medicine, working with biochemists, geneticists and clinicians at the University of Bern, Switzerland and in the United Kingdom, have discovered an enzyme that has a key role in inflammatory bowel disease (IBD). The team, co-led by Judith Bond, Ph.D., Distinguished Professor and Chair of Biochemistry and Molecular Biology at Penn State College of Medicine, and Daniel Lottaz, Department of Rheumatology and Clinical Immunology at the University of Bern, Switzerland, could potentially lead to therapies to help the half-a-million Americans affected by ulcerative colitis and Crohn's disease, collectively referred to as IBD.

The enzyme, coded for by the MEP1A gene, is a zinc-containing metalloprotease called meprin, and is abundant in the intestine. A protease is an enzyme that breaks down proteins in the body.

Researchers at Penn State College of Medicine studied the role of meprin in IBD using genetically altered mice lacking the ability to produce the enzyme in collaboration with colleagues in Switzerland who studied the enzyme in IBD patients. Meprin is abundant in the latter part of the small intestine, or terminal ileum, and is also present in the large intestine at a lower level. The European researchers found an alteration in the meprin gene that correlated with IBD. They then compared the levels of meprin in affected and unaffected sections of colons from IBD patients and from healthy people. The amount of enzyme in the IBD patient's inflamed colon was significantly lower than that in normal colon sections. The researchers concluded that their findings strongly correlate the severity of inflammation associated with both Crohn's disease and ulcerative colitis with low meprin levels.

This discovery is a major advance in understanding the genetic control of inflammation, and of ulcerative colitis and Crohn's disease in particular, Bond said. She discovered meprin more than 25 years ago while at the Medical College of Virginia Commonwealth University. Since then, she has studied the structure and activities of the meprins and has located the genes for the subunits in both the mouse and human chromosomes. After coming to Penn State Hershey in 1992, her studies have focused on the biomedical significance of the meprin proteases. With colleagues from the National Institutes of Health, she found a linkage between the meprin gene and vulnerability to diabetic nephropathy in Pima Indians in the southwestern United States.

These types of transitional research that provide sound basic understanding of a disease process, coupled with detailed examination and critical interpretation of clinical findings, are dependent upon sustained collaborations based upon trust and respect, Bond said. Before this international effort, she teamed up with kidney specialists at Albert Einstein College of Medicine in New York and with W. Brian Reeves, M.D., at Penn State Hershey to demonstrate that meprin influences the outcome of acute renal failure in mice.

The Penn State researchers used a mouse model of IBD, replicating inflammation in the intestine like that in human ulcerative colitis. Mice lacking meprin had more severe intestinal damage after drinking a solution to induce inflammation, than did the wild-type mice that have meprin. These results indicate that meprin reduces the level of inflammation in the injured intestine.

In the mouse model, it is possible to make detailed measurements on a number of consequences of inflammation. Nitric oxide in the blood is an important host defense against bacterial infection, but its power as an oxidant also damages host tissue. A nitric oxide level in the blood of mice lacking meprin was much higher than the level in wild-type mice. The Penn State team also discovered that meprin is able to activate an inflammatory serum factor produced by white blood cells, and this factor is elevated in both the mouse model of IBD and in humans with active IBD. Bond explained, The defect in the human meprin gene most associated with ulcerative colitis is in a region that regulates production of the meprin protein.

The researchers concluded that a particular defect in the MEP1A gene is an indicator of vulnerability to IBD, particularly ulcerative colitis. The association of the meprin gene with Crohn's disease remains to be characterized but disruption of the meprin gene affects the severity of both ulcerative colitis and Crohn's disease. Bond summarized the findings by saying, There's the possibility of predicting who will be susceptible to IBD, and diagnosing the disease with this information. If we could increase meprin production, or replace it with an equivalent enzyme, there are therapeutic possibilities. More studies are needed to understand how meprin influences inflammation, but this is the first association of meprin levels as a key factor in the severity of IBD.

No longer afraid to be a bridesmaid or travel with the boss

Wed, 13 May 2009 04:00:00 PST

( from http://www.rxpgnews.com ) CHICAGO --- One of Laurie Keefer's patients was afraid to be a bridesmaid in a friend's wedding, others worried about traveling with the boss or even going to parties in peoples' homes.

The patients have ulcerative colitis, a nasty gastrointestinal disease that flares without warning and makes it vital for them to find a bathroom fast. The disease is often diagnosed when people are in their late 20s and early 30s. The flare-up is like having a severe stomach bug that can drag on for weeks. It ruins vacation plans, causes lengthy absences from work and generally messes up peoples' lives at a time when they are trying to build careers and meet a romantic partner or marry.

But some of Keefer's patients are less fearful these days and starting to embrace activities they once avoided. They've been taking part in a new National Institutes of Health (NIH) funded research study to test whether hypnotherapy can extend the time between their flare-ups. Currently, the treatments for ulcerative colitis, an inflammatory bowel disease, include a fistful of pills -- up to a cumbersome 12 a day that reduce the risk of flares but that many forget to take, as well as steroids or surgery to remove their colon.

In an early look at the data for the ongoing study, Keefer, a clinical health psychologist and an assistant professor of medicine at the Northwestern University Feinberg School of Medicine, is finding that treatment with hypnotherapy enabled some subjects' to socialize more and get involved in activities such as eating at restaurants, exercising and road trips. Some subjects feel less impaired by their disease and are better at remembering to take their pills.

The patient who was afraid to stand up at a friend's wedding is now going to be a bridesmaid. The patient who was nervous about getting on a plane with the boss is now taking business trips with him.

The study will be enrolling a total of 80 patients over three years and will track the progress of each patient for one year. Thus far, 27 subjects have enrolled in the study and completed the required eight weeks of hypnotherapy sessions. As a part of the study, subjects also listen to special relaxation tapes up to five times per week.

While it's too early in the study to know if the hypnotherapy has prolonged their remissions, only two of 12 subjects who have participated in the study for a full year have experienced a relapse, whereas based on their history, all 12 subjects would have been expected to have had two or more relapses within the year.

These numbers are encouraging because the study specifically targets individuals who flare a couple times a year, Keefer said. Subjects are also expected to take their routine maintenance medication during the trial.

UIC researchers measure health effects of Chicago's waterways

Mon, 23 Mar 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers at the University of Illinois at Chicago School of Public Health are conducting a study to determine the health effects associated with recreational activities such as boating, canoeing, kayaking and fishing on Chicago's waterways.

The Chicago Health, Environmental Exposure, and Recreation Study, or CHEERS, is funded by the Metropolitan Water Reclamation District of Greater Chicago.

The project aims to determine the rate of illness for people who participate in water activities other than swimming and establish water quality standards for people who enjoy activities on the waterway.

Local and federal regulations have been developed to protect people who swim at beaches, but water quality standards do not exist to protect people who row, paddle, boat or fish. This is the first study in the U.S. to evaluate health and environmental factors associated with recreation on water.

The researchers are enrolling people who participate in activities on Chicago area waterways and will follow them over time to see if they get sick, according to Dr. Samuel Dorevitch, research assistant professor of environmental and occupational health sciences at UIC and principal investigator of the study.

We also have a comparison group of people who are outdoors on the same days at about the same places doing recreational activity that doesn't involve water, Dorevitch said. By comparing the two, the researchers hope to uncover any short-term health effects of water recreation, such as gastrointestinal infections, skin infections, or eye, ear or respiratory conditions.

Participants will be surveyed before and after activities on the water. The amount of water swallowed, inhaled, or splashed on skin will also be measured in some people. Two of the novel ways for measuring water exposure were developed at UIC.

Aerosol samplers will be used to measure the amount of water that people may be inhaling during water sports. Sponges clipped to the shirts of subjects will show how much water the skin is exposed to, Dorevitch said. Amounts of water ingested during recreational activity will be measured at several local swimming pools.

Study participants will then receive phone calls over three weeks following exposure to see if they have developed any symptoms or infections.

A unique aspect of the study is that the researchers will measure the actual pathogens in the water that cause disease, Dorevitch said. Most prior research has looked at indicators of sewage pollution in the water, like E. coli bacteria.

It's not usually E. coli that makes people sick, Dorevitch said. But the presence of E. coli in the water indicates that there may be sewage contamination.

The new study, he said, will measure not only E. coli, but also such pathogens as giardia, cryptosporidium and norovirus that actually do make people sick.

Putting a name to the fluke

Wed, 11 Feb 2009 05:00:00 PST

( from http://www.rxpgnews.com ) In a world first, a UQ researcher has developed a non-invasive screening method for potentially fatal liver and intestinal flukes plaguing the lives of an estimated 9 million people throughout southeast Asia.

The PCR test is already being used by Thai researchers to screen people for the presence of three species of liver and intestinal flukes which range in length from a few millimetres to one centimetre.

The highly accurate test can identify the species involved from one gene from an egg of a fluke among billions of other genes in a single faecal sample.

Dr Rebecca Traub and Dr Julie Macaranas, from UQ's School of Veterinary Science, developed the test after field work in Thailand, testing samples from more than 300 people in a remote village, 150km east of Bangkok.

Other researchers involved with the project included Dr Mathurit Mungthin from Phramongkutklao College of Medicine in Bangkok, Professor Darwin Murrell from the Danish Centre for Experimental Parasitology and Professor Andrew Thompson from Murdoch University.

To develop the molecular-based test, Dr Traub also called on the parasite identification expertise of UQ's Associate Professor Tom Cribb, from the Centre of Marine Studies, once back in the labs at the St Lucia campus.

The breakthrough test is a vast improvement existing testing methods to identify the flukes, involving a painful process of inducing people to purge the fully grown flukes.

The test also allows authorities to more effectively handle infestations once they know the particular species, its life cycle and host animals if any.

Dr Traub's research was funded by a three-year, Australian Research Council Linkage grant with Bayer Animal Health GmbH as the industry partner.

The leaf-shaped flukes enter the human digestive tract though consumption of raw fish, an important cultural practice which continues despite authorities warning against it.

The creatures' life cycle involve marine snails and even dogs and cats depending on the species of fluke.

In extreme cases, the flukes can cause cancer of the bile duct and/or painful stones in the bile duct, leading to liver disease and even death.

Dr Traub said her research was important because 70 percent of the world's emerging infectious diseases involved an animal source or host. Examples include Hendra Virus, SARS, Avian Flu and Hydatid Disease.

Multi-disciplinary research teams engaged in public health research are increasingly adopting a 'One Medicine' approach involving medical doctors, veterinarians and biologists. This is the most effective way of tackling the understanding and control of such diseases, Dr Traub said. She said she would seek further ARC or Wellcome Trust funding for the next stage of her research.

14.6% of patients with Iron deficiency anaemia of obscure origin have gluten sensitive enteropathy (GSE

Wed, 31 Dec 2008 08:13:26 PST

( from http://www.rxpgnews.com ) Gluten sensitive enteropathy (GSE) is an autoimmune enteropathy due to food gluten intolerance in genetically predisposed people. While GSE was thought to be a rare disease in the past and was believed to be essentially a disease of Europeans, recent screening studies showed that GSE is one of the most frequent genetically based diseases occured worldwide. Iron deficiency anemia could be a sole manifestation of GSE, and it might result in the delayed diagnosis of GSE, resulting in complications.

A research team led by Prof. Reza Malekzadeh studied the prevalence of gluten sensitive enteropathy (GSE) in a large group of patients with iron deficiency anemia (IDA) of obscure origin. Their findings will be published on December 28, 2008 in the World Journal of Gastroenterology.

In this prospective study, 4120 patients with IDA were enrolled in this study. Anti-endomysial antibody (EMA) and tissue transglutaminase antibody (tTG) levels were evaluated and duodenal biopsies were taken and scored according to the Marsh classification. The diagnosis of GSE was based on a positive serological test and abnormal duodenal histology. Gluten free diet (GFD) was advised for all the GSE patients.

Of the 4 120 IDA patients, 206 (95 male) patients were found to have IDA of obscure origin. Thirty out of 206 patients (14.6%) had GSE. Sixteen patients had Marsh 3, 12 had Marsh 2, and 2 had Marsh 1 lesions. The severity of anemia was in parallel with the severity of duodenal lesions. Twenty-two GSE patients (73.3%) had no gastrointestinal symptoms. Fourteen GSE patients who adhered to GFD without receiving iron supplementation agreed to undergo follow up visits. After 6 mo of GFD, their mean hemoglobin levels (Hb) increased from 9.9 ± 1.6 to 12.8 ± 1.0 g/dL (P < 0.01). Interestingly, in 6 out of 14 patients who had Marsh 1/2 lesions on duodenal biopsy, mean Hb increased from 11.0 ± 1.1 to 13.1 ± 1.0 g/dL (P < 0.01) while they did not receive any iron supplementation. These results indicate that there is a high prevalence of GSE in patients with IDA of obscure origin. Gluten free diet can improve anemia in GSE patients who have mild duodenal lesions without villous atrophy.

Novel IBS treatment developed at UB garners $8.5 million for seven-year clinical trial

Thu, 13 Nov 2008 05:00:00 PST

( from http://www.rxpgnews.com ) BUFFALO, N.Y. -- Irritable bowel syndrome is a chronic, debilitating disorder affecting 25 million people in the U.S -- 14-24 percent of women and 5-19 percent of men.

No reliable and satisfactory medical treatment exists for the full range of IBS symptoms, which can cause severe physical and psychological distress and deprive sufferers of their quality of life.

Based on a successful pilot study of a primarily at-home, self-administered cognitive behavior therapy program, a University at Buffalo behavioral scientist has received $8.5 million from the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) to conduct a seven-year, multi-site clinical trial of the program developed at UB.

The UB trial is the largest IBS clinical trial conducted to date and one of the largest behavioral trials funded by the NIH.

Jeffrey M. Lackner, Psy.D., assistant professor in the department of medicine, UB School of Medicine and Biomedical Sciences, and director of its Behavioral Medicine Clinic at Erie County Medical Center, is principal investigator.

The trial will be conducted at three sites: UB, University at Alabama-Birmingham and Northwestern University. Following a 12-month planning period, 480 patients between the ages of 18 and 70 with moderate to severe IBS will be recruited over the following four years. Participants will be assigned randomly to one of three treatment groups: standard cognitive behavior therapy (CBT), in which patients will receive 10 weekly one-hour sessions with a therapist; home-based CBT plus 4 one-hour therapist sessions over 10 weeks; or education and support.

Participants will be reassessed at five points during the 12 months following the intervention to determine the long-term effectiveness of each treatment.

In the short term, we hope to show that a self-administered version of cognitive behavior therapy for IBS is as effective as standard in-office treatment, but is more efficient, more accessible and less costly to deliver, said Lackner.

In the long term, we hope to show that a self-administered behavioral treatment program maintains its effectiveness over time, can enhance the quality of patient care, improve clinical outcomes and decrease the economic costs of one of the most prevalent and intractable GI disorders.

Lackner noted that the trial addresses a major priority of the NIDDK of improving the quality of care for IBS and the surgeon general's call to develop relatively simple behavioral approaches for enhancing the long-term health of chronically ill Americans.

UB co-investigators are Leonard Katz, M.D., Michael Sitrin, M.D., Susan Krasner, Ph.D., Changxing Ma, Ph.D., and Ann Marie Carosella, Ph.D. Rebecca Firth is project coordinator.

Lackner's early research leading to an NIH-funded pilot study and the current NIDDK award was supported by an Interdisciplinary Research and Creative Activities grant from the UB Office of the Vice President for Research. In addition, the UB School of Medicine and Biomedical Sciences and Office of the Vice President for Research provided bridge funding to sustain Lackner's research between the pilot study and the NIDDK study.

Factors for developing IPF in Hepatitis C patients

Thu, 23 Oct 2008 14:12:44 PST

( from http://www.rxpgnews.com ) Hepatitis C virus (HCV) is one of the more common causes of chronic liver disease in world with a variety of extrahepatic complications such as essential mixed cryoglobulinemia, membranoproliferative glomerulonep hritis, autoimmune thyroiditis, sialadenitis, and cardiomyopathy. IPF is present in patients with chronic HCV infection. However, there is little or no information on the yearly cumulative incidence and risk factors on the development rate of IPF in patients with HCV.

A research team led by Yasuji Arase from Toranomon Hospital of Japan addresses this question and this will be published on October 14, 2008 in the World Journal of Gastroenterology. In this study, they studied 6150 HCV infected patients who were between 40-70 years old (HCV-group). Another 2050 patients with hepatitis B virus (HBV) were selected as control (HBV-group). The mean observation period was 8.0 ± 5.9 years in HCV-group and 6.3 ± 5.5 years in HBV-group.

They found that fifteen patients in HCV-group developed IPF. On the other hand, none of the patients developed IPF in HBV-group. In HCV-group, the cumulative rates of IPF development were 0.3% at 10th year and 0.9% at 20th year. The IPF development rate in HCV-group was higher than that in HBV-group (P = 0.021). The IPF development rate in patients with HCV or HBV was high with statistical significance in the following cases: (1) patients ≥ 55 years (P < 0.001); (2) patients who had smoking index (package per day × year) of ≥ 20 (P = 0.002); (3) patients with liver cirrhosis (P = 0.042). This result indicated that age, liver cirrhosis and smoking enhance the development of IPF in patients with chronic hepatitis C infection.

Children's Hospital of Pittsburgh of UPMC scientific director elected to Institute of Medicine

Mon, 13 Oct 2008 04:00:00 PST

( from http://www.rxpgnews.com ) David H. Perlmutter, MD, scientific director and physician-in-chief at Children's Hospital of Pittsburgh of UPMC, has been elected to the prestigious Institute of Medicine (IOM).

The IOM was established in 1970 by the National Academy of Sciences as a national resource for independent, scientifically informed analysis and recommendations on health issues. The institute provides unbiased, evidence-based, authoritative information and advice concerning health and science policy to policy-makers, professionals, leaders in every sector of society and the public at large. Election to the IOM is considered one of the highest honors in the fields of health and medicine and recognizes individuals who have demonstrated outstanding professional achievement and commitment to service.

Dr. Perlmutter, the Vira I. Heinz Professor and Chair of the Department of Pediatrics at the University of Pittsburgh School of Medicine, is one of only 65 new members and five foreign associates who are being announced at the IOM's annual meeting Monday, Oct. 13, 2008. Current active members elect new members from among candidates nominated for their professional achievement and commitment to service.

Since joining Children's Hospital in 2001, Dr. Perlmutter has led an effort to expand the hospital's basic and clinical research program so that it is ideally poised to investigate the molecular basis of pediatric disease and to develop innovative new therapies for childhood illnesses. Under his leadership, Children's Hospital has become among the fastest growing pediatric research program in the country in terms of National Institutes of Health (NIH) funding from 2000.

It's a tremendous honor to be elected to the Institute of Medicine. I view this recognition as a testament to the great people with whom I have had the opportunity to work in my clinical and research lives at several wonderful institutions, Dr. Perlmutter said. As a physician-scientist, I've dedicated my career to improving children's health, through my basic research and clinical care of young patients, and by fostering the development of new generations of physician-scientists and clinicians who are dedicated to child health issues.

Dr. Perlmutter has carried out basic research on alpha-1-antitrypsin deficiency, the most common genetic liver disease of childhood, for more than 20 years. His work has led to many new concepts about the pathobiology of liver disease in this deficiency and has suggested several new concepts for chemoprophylaxis of chronic liver injury, hepatocellular carcinoma and emphysema in this genetic disease. He is the principal investigator on three NIH grants in this area and also now holds four other NIH grants, including the Child Health Research Center of Excellence Award for training pediatric physician-scientists in the molecular basis of pediatric disease.

Election to the Institute of Medicine is a unique and particularly noteworthy recognition of an individual's professional achievements and contributions to the medical sciences and health care. I can think of no one more deserving of such an honor than Dr. Perlmutter, whose basic research has elucidated the fundamental etiology of pediatric liver disease and whose translation of that knowledge into clinical practice has improved the health of countless children, said Arthur S. Levine, MD, senior vice chancellor for the health sciences and dean of the School of Medicine at the University of Pittsburgh. However, it is his mentorship of an emerging cadre of young physician-scientists and his transformation of the University of Pittsburgh Department of Pediatrics into one of the nation's strongest pediatric research enterprises that secure his enduring legacy in medicine and science.

Dr. Perlmutter's research has been recognized by numerous awards including the E. Mead Johnson Award for Research in Pediatrics. He is a member of the American Society for Clinical Investigation and the Association of American Physicians. He has served as the president of the Society of Pediatric Research and is now a member of the Advisory Council of the National Institute for Diabetes, Digestive and Kidney Diseases.

Dr. Perlmutter earned his bachelor's degree from the University of Rochester and his medical degree from St. Louis University School of Medicine. He completed his residency in pediatrics at The Children's Hospital of Philadelphia and his fellowship in pediatric gastroenterology and nutrition at Children's Hospital Boston.

After several years on the faculty of Harvard Medical School, Dr. Perlmutter joined the faculty at Washington University School of Medicine and St. Louis Children's Hospital. From 1992, he was the director of the Division of Gastroenterology and Nutrition at St. Louis Children's, and in 1996 he became the first to hold the Donald Strominger Endowed Professorship of Washington University School of Medicine. In 2001 he left St. Louis to take his current position in Pittsburgh.

Endoscopy not needed in asymptomatic children after caustic ingestion

Fri, 26 Sep 2008 23:52:29 PST

( from http://www.rxpgnews.com ) A new study from researchers in Italy reports that endoscopy may not be necessary in children who show no symptoms after a caustic ingestion. The results demonstrated that the incidence of severe abnormalities of the esophagus in children without any early symptoms is very low and an endoscopy could be avoided. The study appears in the September issue of GIE: Gastrointestinal Endoscopy, the monthly peer-reviewed scientific journal of the American Society for Gastrointestinal Endoscopy (ASGE).

In the pediatric population, the ingestion of caustic substances remains a difficult problem to assess because of the unclear relationship between signs and symptoms, and the extent of esophageal damage. The most efficient method for assessing the upper-gastrointestinal tract lining after a caustic ingestion is an upper endoscopy, or esophogogastroduodenoscopy (EGD). An important characteristic of cases of ingestion in the pediatric age group is that they are generally accidental, whereas in adolescents and adults, the substance was usually deliberately ingested.

"Whether or not an urgent endoscopy should be performed on children after a caustic ingestion is still a matter of debate, particularly in asymptomatic patients," said study lead author Pietro Betalli, MD, University of Padova, Padova, Italy. "Our study looked to determine if the symptoms at presentation can predict the presence of esophageal lesions. We found that the risk of severe damage increased proportionally with the number of signs and symptoms, indicating that an endoscopy should always be performed in symptomatic patients."

Patients and Methods

The multicenter observational study was conducted from January 2005 to January 2007 at hospitals in 10 Italian cities. A total of 162 children, mostly infants and toddlers, who were seen at the emergency center for caustic substance ingestion were enrolled. All cases involved accidental ingestion. An EGD was performed in children younger than 15 years old within 12 to 24 hours from the ingestion. A form was completed for each child in the emergency department by a trained pediatrician who collected information on the patient, the substance involved, and signs and symptoms. Signs and symptoms were graded as minor (oral and/or oropharyngeal lesions, and vomiting) or major (dyspnea, dysphagia, drooling, and hematemesis).

In every EGD, the esophagus, stomach and duodenum were thoroughly examined. Pediatric endoscopes were used and the procedures were performed by experienced endoscopists. Endoscopy reports were reviewed and graded for severity of esophageal injuries by a physician blinded to the initial symptoms using an endoscopic classification system for esophageal burns.

Results

Mild esophageal lesions (e.g., redness) were identified at the time of EGD in 88 percent of children. Severe lesions (third degree such as ulcers or necrosis) were seen in 12 percent of the cases. Furthermore, nine patients had gastric ulcers with all nine also having esophageal abnormalities on the EGD. Children without any signs or symptoms after an ingestion were much less likely to develop significant endoscopic findings than those who had at least three signs or symptoms (odds ratio of 0.13 v. 11.97, respectively). Of those with signs or symptoms, major complaints were more likely than minor complaints to predict esophageal damage. Severe esophageal damage at endoscopy predicted the eventual development of an esophageal stricture (14 out of 19 children).

Researchers concluded that the likelihood of finding severe esophageal damage in patients without any early signs and symptoms was very low, therefore an endoscopy could be avoided. The specific risk of the presence of third-degree lesions rises progressively with increasing numbers of signs and symptoms. The presence of three or more symptoms is an important predictor of esophageal lesions. The study notes that an endoscopy is warranted in all symptomatic children.

How to prevent liver damage induced by anti-tuberculosis treatment?

Fri, 19 Sep 2008 04:00:00 PST

( from http://www.rxpgnews.com ) About one third of the world's population has latent tuberculosis and roughly 9 million cases of active tuberculosis emerge annually resulting in 2-3million deaths. Most new cases occur in the most populated nations like India and China. Combination chemotherapy containing Isoniazid (INH), Rifampicin (RMP), Pyrazinamide (PZA) with or without ethambutol for initial 2 months followed by a continuation phase of 4-6 months of Isoniazid and Rifampicin is the preferred regimen for successful treatment and for preventing acquired resistance. Drug induced hepatotoxicity is a potentially serious adverse effect of antituberculosis (ATT) regimen. A higher risk of hepatotoxicity has been reported in Indian patients (up to 11.5%) than in their western counterpart (up to 4.3%). The only measure available for managing hepatotoxicity is stopping the offending agents, once there is an evidence of liver damage and reintroducing the same after normalization of liver enzymes. Preventive therapy of contacts causes severe hepatotoxicity more often than curative treatment of clinical tuberculosis. Search for non-toxic and highly effective new compounds for treating tuberculosis or an effective vaccine conferring sustained protective immunity have yet not seen the face of success.

A research article to be published on August 14, 2008 in the World Journal of Gastroenterology addresses this question. The research team led by Dr. Meghna Adhvaryu of Bapalal Vaidya Botanical research center, Departrment of Biosciences, Veer Narmad South Gujarat University Surat, India in joint effort with Dr. Bhasker Vakharia running a charitable mobile clinic in tribal belt of district surat, conducted a clinical trial of two Ayurvedic herbs in a modified form used as an adjuvant to conventional ATT to evaluate their ability to prevent hepatotoxicity.

The pathogenesis of hepatotoxicity is not entirely clear but INH and RMP induced damage may involve oxidative stress, lipid peroxidation, choline deficiency leading to lowering of phospholipids protein synthesis with alteration in cell wall configuration, reduced glutathione level and activation of CYP2E1. It is well known that some non toxic herbs are having opposite activities in the form of membrane stabilizing, anti-oxidative and CYP2E1 inhibitory effects. A review of available literature suggests that reduction in lipid peroxide content in tissue and increase in superoxide dismutase, catalase, glutathione, glutathione-s-transferase and glutathione peroxidase activities should help to maintain liver cell integrity and control the increase in level of liver enzymes.

Initially four potential candidate herbs were tested in a guinea pig model of ATT induced hepato-toxicity and marked hepato-protective ability was demonstrated. The research article was published on 21st June 2007 in the

String probes for devastating childhood digestive disease

Wed, 30 Jul 2008 04:00:00 PST

( from http://www.rxpgnews.com ) A swallowed string may someday replace the invasive, uncomfortable endoscope now used to diagnose a devastating childhood disease of the esophagus.

Steven J. Ackerman of University of Illinois at Chicago College of Medicine and Dr. Glenn T. Furuta, his colleague at the University of Colorado Denver, were recently awarded three grants for an all-fronts attack on eosinophilic esophagitis, an inflammatory disease in which defense cells called eosinophils mistakenly attack the esophagus, causing it to narrow until food can't pass.

Most cases are first encountered in the emergency room, where a child is brought in because something he ate is caught in his esophagus, said Ackerman, professor of biochemistry and molecular genetics at UIC.

To diagnose the disease, doctors insert an instrument called an endoscope down the esophagus and take six to eight samples of tissue, from the top, middle and distal end, near the stomach. Under a microscope, they count the number of eosinophils, which are not normally present in the esophagus at all, Ackerman said. The procedure, he said, is not only expensive but uncomfortable and carries some risks. And because repeat testing is needed over the course of treatment, a child may need to undergo as many as 20 endoscopies within three or four years.

Ackerman and his colleagues hope they can replace the endoscope by having children swallow a string encased in a gelatin capsule. As the capsule travels down the esophagus, the string plays out of the dissolving capsule, stretching through the esophagus, the stomach and the small intestine. The string is left in place overnight, then pulled out.

We can determine which part of the string was in the esophagus, versus in the stomach, mouth or small intestine, said Ackerman. They then look on the string for certain inflammatory proteins that are expressed only by eosinophils.

The test will be done the day before an endoscopic test is planned. The researchers will compare the thread's measures of the eosinophil proteins with the cell counts obtained by endoscopy.

Eventually, of course, our hope is to replace these repeated endoscopies with this simple procedure, Ackerman said.

The study, funded by the National Institute of Allergy and Infectious Diseases (one of the National Institutes of Health), will be done at two sites, UIC and Denver. Ackerman and Furuta are co-principal investigators on the team, which also includes Dr. Amir Kagalwalla of the UIC Department of Pediatrics.

The two other grants are from the American Gastroenterological Association (AGA) and the CURED Foundation (Campaign Urging Research for Eosinophilic Diseases).

The AGA awarded Ackerman and Furuta its 2008 translational research award to determine the mechanisms that regulate changes in the esophagus caused by the disease, including the growth of scar tissue. The researchers will use the string test to look for biomarkers of the changes that characterize the disease.

CURED awarded the team an unrestricted gift for research to investigate pathogenic mechanisms in eosinophilic esophagitis and related gastrointestinal diseases. CURED has raised more than $1.4 million over the past five years, most recently as the beneficiary charity of the annual Highland Park (Ill.) High School fund-raising event, which raised $500,000 this year.

The investigators are also planning a proteomics study that will measure all the proteins on the string to develop a more complete diagnostic profile of the disease, Ackerman said.

These grants present us with an exciting opportunity to increase our understanding of this difficult, newly emerging disease, which has increased in detection, and also possibly in incidence.

Integrins act as receptors to Rotavirus

Mon, 30 Jun 2008 09:07:43 PST

( from http://www.rxpgnews.com ) Eleven years ago, Dr. Mary Estes of Baylor College of Medicine and her colleagues discovered the first viral enterotoxin, rotavirus NSP4, a toxic protein that affects the intestines, causing diarrhoea.

The next step was to find the cellular receptor on intestinal cells through which the enterotoxin interacts to cause diarrhoea.

"We knew that identifying the receptor might not be straightforward," said the professor of molecular virology and microbiology at BCM. In a report online in the Proceedings of the National Academy of Sciences, Estes and her colleagues describe two receptors for the enterotoxin, both of them integrins.

The two, integrin alpha1 beta1 and integrin alpha2 beta1, are members of a class of molecules that are involved in attaching cells to other cells and to the extracellular matrix (a part of tissue that is not part of any cell). Integrins also are involved in transforming or translating cell signals.

In looking for the receptor, Estes and her colleagues also learned more about the enterotoxin itself.

"It's a new ligand for binding to integrins," she said. "It begins to give us an understanding of how the enterotoxin works in the intestine. Two different domains of the enterotoxin are involved in this interaction. One domain is for binding and the other domain is for signaling through the receptor."

She said she hopes to study the signaling aspect of the enterotoxin more closely because it could hold the clue to the mechanism of induction of diarrhoeal disease.

"There may be ways to block the interaction between the enterotoxin and the receptor to treat diarrhoeal disease," said Estes, who is also director of the Texas Medical Center Digestive Diseases Center.

Rotavirus is one of the most common causes of diarrhoea, resulting in approximately 3 million cases of diarrhoea and 55,000 hospitalizations for diarrhoea and dehydration in children under the age of 5 each year in the United States alone. Worldwide, it causes nearly half a million deaths each year. Finding out how rotavirus causes diarrhoea and looking for ways to block it is a major aim of Estes' research.

NCI grant launches clinical trials for colon cancer screening

Wed, 25 Jun 2008 04:00:00 PST

( from http://www.rxpgnews.com ) EVANSTON, Ill. --- A Northwestern University biomedical engineer who has developed optical technology shown to be effective for the early detection of colon cancer has received a $7.5 million grant over five years from the National Cancer Institute to further study an instrument that potentially could become a routine colon cancer screening test and to launch large-scale clinical trials.

Colon cancer is the second-leading cause of cancer deaths in the United States; more than 50,000 Americans die each year of the disease. Colon cancer, however, can be easily treated if detected early. But no existing population-wide screening test can accurately predict the presence of the disease with adequate sensitivity.

Vadim Backman, principal investigator for the grant and professor of biomedical engineering at Northwestern's McCormick School of Engineering and Applied Science, believes the technology he has developed could lead to the first such test. A major part of the NCI grant is to validate the technology and have it ready for commercialization.

Backman is leading a diverse group of researchers from Northwestern and the four hospitals conducting the clinical trials -- Evanston Northwestern Healthcare, the University of Chicago, Stanford University and Indiana University -- to develop an inexpensive, non-invasive test for routine colon cancer screening.

In the future, it is possible that the simple test would be conducted by a primary care physician during an annual exam. Only patients with abnormal results would go on to have the more invasive and expensive colonoscopy.

The clinical trials will include two studies. The first study of 1,000 patients will be to finalize the technology to be used in the test (making sure it can be used clinically and is practical) and to define the technology's prediction rules; the second will be a double-blind study of 3,000 patients.

The screening test, which does not require bowel preparation, will be done in patients about a week before a colonoscopy. Each person will have a colonoscopy even if the results from the screening test are negative in order to correlate the screening results with the colonoscopy results.

Our hope is that similar to how the routine pap smear drastically reduced deaths from cervical cancer, this new technology could do the same when it comes to colon cancer, said Backman.

Backman's optical technique takes advantage of certain light scattering effects and is minimally invasive. The method can detect abnormal changes in cells lining the colon long before those changes can be seen under a microscope, and even before polyps form.

The extraordinarily sensitive technique involves a simple fiber optic probe roughly the size of a pen being inserted into the rectum. Light shines on the tissue at the base of the colon, scatters and some of that light bounces back to sensors in the probe. A computer analyzes the pattern of light scattering, looking for the fingerprint of carcinogenesis in the nanoarchitecture of the cells.

If you have a precancerous lesion in one part of the colon, said Backman, even tissue that looks normal and is located far from the lesion or polyp will have molecular and other kinds of changes. It's the biological phenomenon called the 'field effect.' No one can detect these changes earlier than we can.

The grant also is funding basic science research to better understand the mechanisms behind the changes in the nanoarchitecture of the cells.

The method combines two complementary technologies developed by Backman and colleagues in his lab: four-dimensional elastic light-scattering fingerprinting (4D-ELF) and low-coherence enhanced backscattering spectroscopy (LEBS).

The grant to Northwestern is part of the National Cancer Institute's Bioengineering Research Partnership (BRP) program and is the only BRP grant funded by the institute this year. A BRP is a multi-disciplinary research team applying an integrative, systems approach to develop knowledge and methods to prevent, detect, diagnose or treat disease.

The site leaders at the four hospitals are Hemant K. Roy, M.D., Evanston Northwestern Healthcare; David Ruben, M.D., the University of Chicago; Jacque Van-Dam, M.D., Stanford University; and Douglas Rex, M.D., Indiana University.

The three other investigators from Northwestern are Borko Jovanovic, associate professor in preventive medicine at the Feinberg School of Medicine; Xu Li, assistant professor of electrical engineering and computer science and of biomedical engineering; and Allen Taflove, professor of electrical engineering and computer science.

'Addicted' cells provide early cancer diagnosis

Tue, 10 Jun 2008 04:00:00 PST

( from http://www.rxpgnews.com ) Scientists at the Institute of Food Research have detected subtle changes that may make the bowel more vulnerable to the development of tumours.

With support from the Food Standards Agency and the Biotechnology and Biological Sciences Research Council they are investigating whether diet could control these changes and delay or reverse the onset of cancer.

We looked at changes in 18 genes that play a role in the very earliest stages of colorectal cancer, says Professor Ian Johnson at the Institute of Food Research.

We detected clear chemical differences in these genes in otherwise normal tissue in cancer patients.

This represents a new way to identify defects that could eventually lead to cancer.

All cells carry a complete set of instructions for the whole organism in their nuclear DNA, but to define the specialised structure and functions of each particular cell type, genes must be switched on or firmly off, over the course of the cell's life-cycle.

One of the mechanisms controlling the activities of the genes in a cell is the epigenetic code, a set of chemical tags attached to the DNA molecule, marking individual genes for expression, or for silence. It is well known that the abnormal behaviour of cancer cells is partly due to mistakes in this epigenetic code, some of which switch on genes for growth, whilst others switch off genes that would otherwise cause abnormal cells to destroy themselves.

Scientists at IFR are exploring the possibility that such mistakes in the epigenetic code may begin to occur in apparently normal tissues, long before the appearance of a tumour.

In the current study published in the British Journal of Cancer they measured the numbers of methyl groups attached to DNA taken from the cells lining the large intestine of bowel cancer patients. They found subtle changes that may make the whole surface of the bowel more vulnerable to the eventual development of tumours by causing the 'addiction' of cells to abnormal gene expression.

Some of these changes seem to occur naturally with age, but, supported by the Food Standards Agency, IFR is investigating the possibility that factors in our lifestyle such as diet, obesity and exercise can accelerate or delay DNA methylation as we grow older, thus giving us some degree of control over this vital aspect of our long-term health.

Professor Nigel Brown, Director of Science and Technology at BBSRC said: Basic research in the relatively young field of epigenetics is already contributing to our understanding of human health. Understanding how epigenetic processes work to maintain healthy cells and tissues is the key to long-term health because, as we see here, the breakdown of these normal processes may subsequently cause disease. BBSRC funds a range of research in the field of epigenetics and has been encouraging networking amongst members of the European epigenetics research community.

Weizmann Institute scientists develop a new approach to treating autoimmune disease

Mon, 02 Jun 2008 04:00:00 PST

( from http://www.rxpgnews.com ) In autoimmune diseases, the immune system turns against the body's own tissues and organs, wreaking havoc and destruction for no apparent reason. Partly because the origins of these diseases are so obscure, no effective treatment exists, and the suffering they inflict is enormous. Now Weizmann Institute scientists have developed a method that in the future may make it possible to treat autoimmune diseases effectively without necessarily knowing their exact cause. Their approach is equivalent to sending a police force to suppress a riot without seeking out the individuals who instigated the unrest.

In healthy people, a small but crucial group of immune cells called regulatory T cells, or T-regs, keeps autoimmunity in check, but in people with inflammatory bowel disease (IBD), one of the most common autoimmune disorders, too few of these cells appear in the diseased intestine, and the ones that do fail to function properly. The new Weizmann Institute approach consists of delivering highly selective, genetically engineered functioning T-regs to the intestine. The study was conducted by Dr. Eran Elinav, a physician from Tel Aviv Sourasky Medical Center's gastroenterology institute who is working toward his Ph.D. at the Weizmann Institute, and lab assistant Tova Waks, in the laboratory of Prof. Zelig Eshhar of the Immunology Department.

Relying on Eshhar's earlier work in which he equipped a different type of T cell to zero in on cancerous tumors, the team genetically engineered T-regs, outfitting these cells with a modular receptor consisting of three units. One of these units directed the cells to the intestine while the other two made sure they became duly activated. As reported in the journal Gastroenterology, the approach proved effective in laboratory mice with a disease that simulates human IBD: Most of the mice treated with the genetically-engineered T-regs developed only mild inflammation or no inflammation at all.

The cells produced what the scientists called a 'bystander' effect: They were directed to the diseased tissue using neighboring, or 'bystander' markers that identified the area as a site of inflammation, and suppressed the inflammatory cells in the vicinity by secreting soluble suppressive substances.

The scientists are currently experimenting with human T-regs for curing ulcerative colitis and believe that in addition to IBD, their 'bystander' approach could work in other autoimmune disorders, even if their causes remain unknown. They also think the method could be valuable in suppressing unwanted inflammation in diseases unrelated to autoimmunity, as well as in preventing graft rejection and certain complications in bone marrow and organ transplantation, in which inflammation is believed to play a major role.

A better method is found for the treatment of patients with portal hypertension

Tue, 20 May 2008 04:00:00 PST

( from http://www.rxpgnews.com ) Bleeding from ruptured esophageal varices is the main complication of portal hypertension and a major cause of death. About one-third of variceal bleeding episodes are fatal while 70% of survivors re-bleed within a year. Propranolol, the drug of choice for primary prevention of variceal bleeding, has been found to be effective in 45% of patients who have never bled, and in only 40% of patients who have had a bleeding episode before. Thus, this drug does not protect a significant number of patients and combination therapy has been advocated as a result. Various drug combinations have been tried, most commonly propranolol with isosorbide mononitrate. However, the problem with combination therapy is an increased incidence of side effects, poor tolerability and lack of compliance. The search for an ideal drug combination that is effective, relatively free from side effects and easy to administer, has been elusive.

Spironolactone, a drug commonly used in cirrhotics with ascites to reduce fluid overload, has been found to have an independent portal hypotensive effect. This drug has been in use for a long period of time and has been found to be safe and free of side effects, except for occasional gynaecomastia.

This study, performed by a team lead by Professor Binay K. De, is described in a research article to be published on March 28, 2008 in the World Journal of Gastroenterology. In the authors' view, the combination of spironolactone with propranolol scores over other combinations for variceal re-bleed, because of the different mechanisms of action of the two drugs and some of the unique properties of spironolactone.

Spironolactone has a direct portal hypotensive effect in addition to its ability to reduce plasma volume by diuresis. Spironolactone has a direct effect on the vasculature and suppressive effect on immunoactive and inflammatory cytokines, independent of its anti-aldosterone effect. An antifibrotic property has also been evidenced experimentally in rats. Because it is a long acting drug, a single daily dosage will suffice.

Using a rational study design, portal pressure was measured after hemodynamic stabilization of the patients. The drugs were administered and the effects were re-assessed on day eight. This allowed time for stabilization of drug levels in the plasma and also provided us information on the early portal hemodynamic changes following drug administration, because the maximal risk of re-bleeding is during the first two weeks.

However, further research using a larger number of patients with a long term follow up is warranted before declaring this combination to be the choice of treatment in preventing variceal re-bleeding.

Synergistic growth inhibitory effect of herbal extracts against HCC and lung cancer cells

Wed, 30 Apr 2008 04:00:00 PST

( from http://www.rxpgnews.com ) Several herbs with diversified pharmacological properties are known to be rich sources of chemical constituents that may have potential for the treatment of several human cancers. Data from the Department of Preclinical Science, Faculty of Medicine, Thammasat University, demonstrates that the growth inhibitory activity of doxorubicin or cisplatin, as single agents, may be modified in combination with emblic myrobalan or belleric myrobalan extracts and may be synergistically enhanced in some cases.

An article to be published on March 14, 2008, in the World Journal of Gastroenterology demonstrates the combination of effective phytochemicals with chemotherapeutic agents. A study was conducted by Khosit Pinmai of Thammasat University, in which he evaluated the interaction of myrobalan extracts with chemotherapeutic drugs on cancer cell growth by isobologram and the combination index (CI) method of Chou-Talalay.

Several studies have shown that doxorubicin and cisplatin have harmful effects on health and can lead to the development of primary and secondary drug resistance in tumor cells, thereby limiting the clinical success of cancer chemotherapy. Recent reports show that combination chemotherapy is a superior modality and that naturally occurring dietary supplements with known anti-cancer properties could be used in combination chemotherapy to reduce the systemic toxicity of chemotherapeutic agents.

The study provides corroborative evidence, as it shows that emblic myrobalan and belleric myrobalan extracts were selectively toxic against two cancer cell lines and that in combination with doxorubicin and cisplatin produced an increased growth inhibitory effect in both hepatocellular carcinoma (HEpG2) and lung cancer (A549) cells. When using synergistic drug combinations at corresponding dose levels, the calculation of the dose reduction index (DRI) at the IC50 demonstrated possible reductions in doxorubicin concentrations for the drug combinations, ranging from 1.64-fold (myrobalan + doxorubicin in A549) to 4.69-fold (myrobalan + doxorubicin in HEpG2). The dose reduction level was different and specific to each combination and cell line. These findings support the hypothesis that combinations of plant extracts and chemotherapeutic agents allow a reduction in the dosage of the latter (e.g., doxorubicin and cisplatin), while retaining the benefits but minimizing the cytotoxic effects, thus enhancing therapeutic efficacy.

In the view of the authors, the mechanism of interaction between myrobalan extracts and chemotherapeutic drugs is unclear, and it is possible that multiple compounds in the myrobalan extracts are involved. Previously, phytochemical studies have shown that myrobalan contains a variety of chemical components, including hydrolysable tannins (e.g., emblicanin, gallic acid and ellagic acid).

Further studies are needed to assess the underlying mechanism(s) and signal transduction pathways leading to growth inhibition induced by single agents and combinations both in vitro and in vivo.

India unveils zinc tablet to control diarrhoea

Mon, 07 Apr 2008 19:55:20 PST

( from http://www.rxpgnews.com ) New Delhi, April 7 - India Monday unveiled a zinc dispersible tablet to control diarrhoea, a disease that kills nearly 500,000 children in the country every year.

Minister of Science and Technology Kapil Sibal said that the use of zinc along with oral rehydration therapy - is recommended by the World Health Organisation - to decrease the incidence and severity of diarrhoea.

'The government has adopted a policy to use zinc in treatment of diarrhoea under the National Rural Health Mission for children below five years of age,' Sibal said.

The minister said the department of biotechnology and WHO have developed simple, easily dispersible and low-cost zinc tablets for the national programme.

The tablets will be given to children between the age of two months and five years. Experts said the dispersible tablets can be administered by mixing with breast milk or water.

The treatment should be started from the first day of diarrhoea and the 14-day course should be completed.

The tablet contains 20 mg of elemental zinc as active ingredient and will be available in sweet vanilla flavour.

The tablet will be produced with technology transfer from Nutriset, a French company. The Nutriset product has been tested in India and clinical trials have evaluated the efficacy of zinc supplements and safety.

Bharat Immunologicals and Biologicals Corporation Limited -, a public sector undertaking of the ministry, will produce the tablet in India.

BIBCOL is ready with the tablet manufacturing facility and a trial batch has been produced. The company has a production capacity of 240 million tablets per annum and will soon come with commercial production.

What change does prokineticin 2/Bv8 have in human hepatocellular carcinoma?

Tue, 18 Mar 2008 04:00:00 PST

( from http://www.rxpgnews.com ) Liver hepatocarcinoma is a highly vascularized cancer, and more and more research is focused on the molecules controlling angiogenesis. In 2001, two novel peptides, known as prokineticin 1/EG-VEGF (PK1/EG-VEGF) and prokineticin 2/Bv8 (PK2/Bv8), were identified, as having potent angiogenic activities. The angiogenic potential of these two peptides during human hepatocellular carcinoma progression was evaluated. These findings show, that only, PK2/Bv8 is expressed in liver and -- surprisingly -- that its expression decreases during hepatocellular carcinoma. Furthermore, these results show that PK2/Bv8 expression is restricted specifically to liver resident macrophages, thus suggesting a role in Kuppfer cell physiology.

This study, performed by a team lead by Dr. Michel Samson and his colleagues at the INSERM U620 unit located at the University of Rennes, to be published on February 28, 2008 in the World Journal of Gastroenterology.

Angiogenesis has become a promising anti-cancer strategy, because in adults novel blood vessels are only formed as the tumor is growing, and not in the surrounding healthy tissue. Identifying novel molecules involved in tumoral angiogenesis will, therefore, allow for new therapeutic targets. PK1/EG-VEGF and PK2/Bv8 are novel peptides with potent angiogenic effects. They have been shown to be upregulated in several types of cancer such as neuroblastoma, prostate, and leydig cell tumors. However, there angiogenic potential has not yet been studied in the context of hepatocellular carcinoma.

According to the authors of the study, the data shown in this work are consistent with the fact that the biology of these two novel peptides is both complex and diverse. Indeed, results were surprising since, instead of observing an upregulation in hepatocellular carcinoma, the team observed a significant downregulation, and the cellular expression was not located to endothelial cells but to resident macrophages. It seems that in liver PK2/Bv8 behaves more like a cytokine than an angiogenic factor, a biological activity that has already been observed in other reports.

Recently, the first anti-angiogenic therapy, which targets secreted VEGF, has been approved by the FDA and is now used as a first line of defense in association with chemotherapy in certain types of cancer. Identifying new molecules involved in tumoral angiogenesis might in turn provide new targets for anti-angiogenic therapeutics. Furthermore, not all the molecular mechanisms underlying hepatocellular carcinoma angiogenesis are entirely understood yet. Our data show that the two novel angiogenic peptides PK1/EG-VEGF and PK2/Bv8 are not involved in hepatocellular carcinoma angiogenesis.

In this study, in order to evaluate the angiogenic potential of PK1/EG-VEGF and PK2/Bv8, gene expression was measured by real-time PCR on a human cohort counting 28 hepatocellular carcinoma patients (provided by the Centre de Ressources Biologiques de Rennes). Furthermore, PK2/Bv8 protein expression was detected in both normal liver tissue, and in isolated liver cells using antibodies anti-PK2/Bv8 provided by Dr. Feige from the INSERM U878 unit in Grenoble, France. This research was performed by doctors from the INSERM U620 Laboratory of toxicology and tissue repair of the Faculty of Pharmacy at the University of Rennes 1, France. This research was funded by INSERM, the Ministre de loEducation Nationale de la Recherche et de la Technologie, and the Region Bretagne.

Further research should explain more precisely how PK2/Bv8 is involved in Kupffer cell physiology.

Alcohol consumption and polymorphisms of cytochromes P4502E1 are high risks for ESCC

Thu, 13 Mar 2008 04:00:00 PST

( from http://www.rxpgnews.com ) Heavier alcohol consumption increases the risk of ESCC. There are synergetic interactions among alcohol drinking and ALDH2, ADH1B, CYP2E1 genotypes. The risk of ESCC in moderate-to-heavy drinkers, ALDH2 (1/2) combined with the ADH1B (1/1) genotype; ALDH2 (1/2) combined with the CYP2E1 (c1/c1) genotype; leads to synergetic interactions, higher than drinkers with ALDH2 (1/1) + ADH1B (1/2 + 2/2); ALDH2 (1/1) + CYP2E1 (c1/c2 + c2/c2).

This study, performed by a team led by Dr. Yan-Mei Guo, is described in a research article published in the March 7, 2008 issue of the World Journal of Gastroenterology.

ESCC is the seventh leading cause of cancer deaths worldwide. Epidemiologic studies have demonstrated that drinking alcoholic beverages is causally related to the development of ESCC. The genetic polymorphisms of Cytochromes P4502E1 (CYP2E1), aldehyde dehydrogenase-2 (ALDH2) and alcohol dehydrogenase-1B (ADH1B; previously called ADH2) affect the metabolism of alcohol. There were some other studies examining the roles of alcohol, CYP2E1, ALDH2 and ADH2 in ESCC. Their findings, however, were contradictory.

In the view of the authors, no clear explanation has, to date, existed to elucidate the susceptibility conferred by CYP2E1, ALDH2 and ADH1B genetic polymorphisms on ESCC. Neither have a definition and evaluation been found to explain the individual and combined roles of these genes and alcohol consumption.

The innovative aspect of this study was the way it looked at the interaction between the CYP2E1, ALDH2 genotype and heavy alcohol drinking, with case-control designs. Previous studies have not examined this issue in detail and to our knowledge this is the first study to show a significant interaction between the CYP2E1, ALDH2 genotype and alcohol drinking. We found there was synergetic interaction with polymorphisms of CYP2E1, ALDH2 genotype and heavy alcohol drinking. Individuals with combined ALDH2 (1/2) and CYP2E1 (c1/c1) genotype showed a dramatically increased risk of ESCC, which is higher than that due to the respective genotypes.

The susceptibility of alcohol and aldehyde dehydrogenase genotypes on ESCC became evident in 2003 when it became widely accepted that alcoholic beverages are causally related to cancer of the esophagus. A review of case-control studies of the effects of ALDH2 and ADH2 genotypes shows consistently positive associations between inactive heterozygous ALDH2 and the risk for esophageal cancer in East Asian heavy drinkers. Only the ALDH2 genotype has been demonstrated to have a critical role in the development of ESCC.

Using an elegant study design, including 80 male patients with esophageal cancer and 480 controls (age and sex matched), the consumption of alcohol and the genetic polymorphism of enzymes involved in the metabolism of ethanol was examined. This research was performed by doctors from the Laboratory of Gansu College of Traditional Chinese Medicine, Lanzhou, China and from the Laboratory of First hospital of Lanzhou University, Lanzhou, China.

Scientists successfully treat new mouse model of inflammatory bowel disease

Thu, 06 Mar 2008 05:00:00 PST

( from http://www.rxpgnews.com ) March 6, 2008 -- Researchers trying to improve cancer immune therapy have made an unexpected find: They've produced the most accurate mouse model to date of inflammatory bowel disease (IBD), a cluster of conditions that afflict approximately 1.4 million Americans with abdominal pain, constipation and diarrhea.

The two most common forms of IBD are Crohn's disease and ulcerative colitis (UC); in extreme cases, they can be fatal. The mouse model closely resembles the most serious form of human UC and is uniformly fatal. But scientists successfully treated the mice with a pair of broad-spectrum antibiotics, easing gut inflammation and increasing survival. The results, reported this week in Public Library of Science-Medicine, have researchers eager to follow up both in the clinic and the lab.

The antibiotics we gave the mice were used individually in unsuccessful clinical trials as ulcerative colitis treatments, but now we have colleagues who are thinking of giving combined therapy an informal try, says co-senior author Thaddeus S. Stappenbeck, M.D., Ph.D., assistant professor of pathology and immunology and of developmental biology. The antibiotics probably won't be a cure by themselves, but they may provide us with a potent new approach to combine with other therapies.

The mice may also allow scientists to learn which species of gut microorganisms are becoming embroiled in battles with host immune systems, triggering the symptoms of UC. That information could allow the development of stronger and more specific treatments.

Silvia Kang, a former graduate student in the laboratory of co-senior author Paul Allen, Ph.D., the Robert L. Kroc Professor of Pathology and Immunology, created the mouse model by crossbreeding two mouse lines they had developed for cancer immune therapy research. Each mouse line had one protein knocked out that restrained immune T cells from shifting into attack mode.

The idea was to see if we could create super killer T cells we could use to attack tumors, says Allen. But all the mice became sick early on, started to lose weight and we soon realized that they all had serious gastrointestinal issues.

Allen decided to consult with Stappenbeck, an expert in IBD.

I've looked at quite a few proposed mouse models of IBD, and I recognized right away that this had the potential to be outstanding, says Stappenbeck. The colons of the mice were incredible. They were filled with inflammatory T cells. We found the mice almost exactly replicated the most acute types of ulcerative colitis.

Unlike prior models of IBD, the mice consistently develop gastrointestinal problems within a short time period and at a predictable point in their lifespan. When researchers treated the mice at three weeks with the antibiotics ciprofloxacin and metronidazole, colon inflammation was reduced and the mice were able to gain weight and survive longer.

Scientists believe IBD results from the host immune system damaging the tissues of the gut while erroneously attacking food and gut microorganisms that aid food digestion. There are an estimated 500 different species of microbes living in the gut, so sorting out which species are being attacked by the immune system has been an imposing challenge.

The new model may significantly ease that challenge. Although the dual antibiotics used to treat the mice are broad-spectrum, they didn't sterilize the guts of the mice, suggesting that the treatment happened to eliminate the microorganisms causing IBD.

We'd like to treat the mice and then reintroduce candidate microorganisms into their guts to see if this restarts the inflammatory reaction, says Stappenbeck.

Stappenbeck and Allen plan continued collaborative study of the model.

Type 2 diabetes may be caused by intestinal dysfunction

Wed, 05 Mar 2008 05:00:00 PST

( from http://www.rxpgnews.com ) NEW YORK (March 5, 2008) -- Growing evidence shows that surgery may effectively cure Type 2 diabetes -- an approach that not only may change the way the disease is treated, but that introduces a new way of thinking about diabetes.

A new article -- published in a special supplement to the February issue of Diabetes Care by a leading expert in the emerging field of diabetes surgery -- points to the small bowel as the possible site of critical mechanisms for the development of diabetes.

The study's author, Dr. Francesco Rubino of NewYork-Presbyterian Hospital/Weill Cornell Medical Center, presents scientific evidence on the mechanisms of diabetes control after surgery. Clinical studies have shown that procedures that simply restrict the stomach's size (i.e., gastric banding) improve diabetes only by inducing massive weight loss. By studying diabetes in animals, Dr. Rubino was the first to provide scientific evidence that gastrointestinal bypass operations involving rerouting the gastrointestinal tract (i.e., gastric bypass) can cause diabetes remission independently of any weight loss, and even in subjects that are not obese.

By answering the question of how diabetes surgery works, we may be answering the question of how diabetes itself works, says Dr. Rubino, who is a professor in the Department of Surgery at Weill Cornell Medical College and chief of gastrointestinal metabolic surgery at NewYork-Presbyterian/Weill Cornell.

Dr. Rubino's prior research has shown that the primary mechanisms by which gastrointestinal bypass procedures control diabetes specifically rely on the bypass of the upper small intestine -- the duodenum and jejunum. This is a key finding that may point to the origins of diabetes.

When we bypass the duodenum and jejunum, we are bypassing what may be the source of the problem, says Dr. Rubino, who is heading up NewYork-Presbyterian/Weill Cornell's Diabetes Surgery Center.

In fact, it has become increasingly evident that the gastrointestinal tract plays an important role in energy regulation, and that many gut hormones are involved in the regulation of sugar metabolism. It should not surprise anyone that surgically altering the bowel's anatomy affects the mechanisms that regulate blood sugar levels, eventually influencing diabetes, Dr. Rubino says.

While other gastrointestinal operations may cure diabetes as an effect of changes that improve blood sugar levels, Dr. Rubino's research findings in animals show that procedures based on a bypass of the upper intestine may work instead by reversing abnormalities of blood glucose regulation.

In fact, bypass of the upper small intestine does not improve the ability of the body to regulate blood sugar levels. When performed in subjects who are not diabetic, the bypass of the upper intestine may even impair the mechanisms that regulate blood levels of glucose, says Dr. Rubino. In striking contrast, when nutrients' passage is diverted from the upper intestine of diabetic patients, diabetes resolves.

This, he explains, implies that the upper intestine of diabetic patients may be the site where an abnormal signal is produced, causing, or at least favoring, the development of the disease.

How exactly the upper intestine is dysfunctional remains to be seen. Dr. Rubino proposes an original explanation known in the scientific community as the anti-incretin theory.

Incretins are gastrointestinal hormones, produced in response to the transit of nutrients, that boost insulin production. Because an excess of insulin can determine hypoglycemia (extremely low levels of blood sugar) -- a life-threatening condition -- Dr. Rubino speculates that the body has a counter-regulatory mechanism (or anti-incretin mechanism), activated by the same passage of nutrients through the upper intestine. The latter mechanism would act to decrease both the secretion and the action of insulin.

In healthy patients, a correct balance between incretin and anti-incretin factors maintains normal excursions of sugar levels in the bloodstream, he explains. In some individuals, the duodenum and jejunum may be producing too much of this anti-incretin, thereby reducing insulin secretion and blocking the action of insulin, ultimately resulting in Type 2 diabetes.

Indeed, in Type 2 diabetes, cells are resistant to the action of insulin (insulin resistance), while the pancreas is unable to produce enough insulin to overcome the resistance.

After gastrointestinal bypass procedures, the exclusion of the upper small intestine from the transit of nutrients may offset the abnormal production of anti-incretin, thereby resulting in remission of diabetes.

In order to better understand these mechanisms, and help make the potential benefits of diabetes surgery more widely available, Dr. Rubino calls for prioritizing research in diabetes surgery. Further research on the exact molecular mechanisms of diabetes, surgical control of diabetes and the role played by the bowel in the disease may bring us closer to the cause of diabetes.

Today, most patients with diabetes are not offered a surgical option, and bariatric surgery is recommended only for those with severe obesity (a body mass index, or BMI, of greater than 35kg).

It has become clear, however, that BMI cut-offs can no longer be used to determine who is an ideal candidate for surgical treatment of diabetes, says Dr. Rubino.

There is, in fact, growing evidence that diabetes surgery can be effective even for patients who are only slightly obese or just overweight. Clinical trials in this field are therefore a priority as they allow us to compare diabetes surgery to other treatment options in the attempt to understand when the benefits of surgery outweigh its risks. Clinical guidelines for diabetes surgery will certainly be different from those for bariatric surgery, and should not be based only on BMI levels, he notes.

The lesson we have learned with diabetes surgery is that diabetes is not always a chronic and relentless disease, where the only possible treatment goal is just the control of hyperglycemia and minimization of the risk of complications. Gastrointestinal surgery offers the possibility of complete disease remission. This is a major shift in the way we consider treatment goals for diabetes. It is unprecedented in the history of the disease, adds Dr. Rubino.

Type 2 diabetes, which accounts for 90 to 95 percent of all cases of diabetes, is a growing epidemic that afflicts more than 200 million people worldwide.

At a time when diabetes is growing epidemically worldwide, Dr. Rubino says that finding new treatment strategies is a race against time. At this point, missing the opportunity that surgery offers is not an option.

Crohn's disease or gastrointestinal endometriosis?

Fri, 22 Feb 2008 08:03:09 PST

( from http://www.rxpgnews.com ) Endometriosis is a condition of unknown etiology in which endometrial tissue occurs at extra-uterine sites, including ovaries, fallopian tubes, and gastrointestinal tract. It usually occurs between 30 and 40 years of age. Four to 17% of menstruating women develop endometriosis. When the disease involves the small bowel, it usually has a benign course, but in rare circumstances, it may present as abdominal emergency. Invasive bowel endometriosis can present as bowel obstruction. The major cause of obstruction is stricture formation and adhesions, which occasionally mimic Crohn's disease or a malignancy in its clinical presentation.

Gastrointestinal endometriosis is suggested by dysmenorrhea, menorrhagia or perimenstrual symptoms. Frank intestinal symptoms are usually associated with intestinal obstruction. While intestinal symptoms may occur during or be exacerbated by the menses, this association may not always be present. The symptoms coincide with menstruation in only 18-40% of the cases. A recurring crampy lower or mid-abdominal pain is the most common presenting symptom for both intestinal endometriosis and Crohn's disease. Other symptoms which may occur in both entities include diarrhea, constipation, nausea, vomiting, fever, anorexia, and weight loss.

A case report published on January 7, 2008 in the World Journal of Gastroenterology describes a desperate patient who presented to Dr. Zafer Teke of Pamukkale University Hospital, Turkey, in 2006. This patient was quite a challenge for Dr. Teke. She was 31 years old with perimenstrual lower and mid-abdominal pain irradiating to the back, and lower abdominal fullness for 3 years, at first monthly, but later continuous, and gradually increasing in severity. She gave a history of moderate dysmenorrhea and menorrhagia, but no dyspareunia. Her only medication was an oral contraceptive. She had delivered a healthy baby.

Her gynecologist at a women's health clinic had diagnosed her with small bowel endometriosis, based on interviews and her clinical course. As only oral contraceptive therapy was started, the symptoms due to partial mechanical bowel obstruction had gradually improved. The lack of response to oral contraceptive therapy had encouraged her gynecologist to perform an exploratory laparotomy. The gynecologist was only able to perform a biopsy from the highly inflamed areas. Biopsy results were non-specific inflammation. The patient was then referred to Dr. Teke's institution to identify the underlying pathology.

In an effort to improve the condition of the patient, Dr. Teke initially decided to treat the patient with conservative measures, and the patient responded to this treatment. However, after ingesting a small amount of food she again complained of abdominal pain, and plain abdominal radiography once more showed mechanical bowel obstruction. After improvement with conservative management and obtaining adequate informed consent, the patient was operated on by Dr. Teke. The operative appearance was thought to indicate Crohn's disease, but in view of the close relationship of the ovaries, tubes and uterus, an immediate gynecological opinion was obtained. The on-call gynecology registrar did not consider the appearance to be due to primary gynecological pathology. An approximately 40 cm segment of distal small bowel had four strictures and three internal fistulas. Histopathological examination of the resected specimen was consistent with Crohn's disease. The surgical treatment led to rapid resolution of the symptoms.

The differential diagnosis of Crohn's disease with intestinal endometriosis may be difficult pre-operatively. Dr. Teke noted that even lower gastrointestinal flexible endoscopy may show no findings suggestive of Crohn's disease, as in his patient. Indeed, there may be a similarity between the two entities in terms of clinical presentation, symptomatology, radiological appearances, surgical and pathological findings. Due to a relatively high percentage of endometriosis among the female population of child-bearing age globally, and the unavailability of a precise test differentiating Crohn's disease from bowel endometriosis, this case reported by Dr. Teke is surely worth the attention of both doctors and women at large.

small intestinal bacteria overgrowthplays a role in nonalcoholic fatty liver disease?

Fri, 22 Feb 2008 07:09:07 PST

( from http://www.rxpgnews.com ) An article recently published in the January 14 issue of the World Journal of Gastroenterology has great significance for NASH. This article will undoubtedly bring about new pathogenesis and treatment of NASH.

Small intestinal bacterial overgrowth has been reported to play a role in the pathogenesis of NASH, endotoxin and TNF-¦Á being the possible mediators. Contrary to this hypothesis, in another study, antibiotic treatment did not normalize aminotransferase levels in NASH patients. This article describes an animal experiment of NASH by Dr. Wan-Chun Wu et al.

A research article to be published on January 14, 2008 in the World Journal of Gastroenterology addresses this question. Dr. Wan-Chun Wu et al established a NASH animal model by a high fat diet for 12 wks successfully, and treated with cidomycin after 8 wks of the high fat diet. A semi-solid colored marker was used for monitoring small intestinal transit. The proximal small intestine was harvested under sterile condition and processed for quantitation for aerobes (E. coli) and anaerobes (Lactobacilli). Liver pathologic score was calculated to qualify the severity of hepatitis. Serum ALT and AST levels were detected to evaluate the severity of hepatitis.

After 12 wks, they had significant findings. Small intestinal transit was inhibited in NASH group. Rats treated with cidomycin had higher small intestine transit rate than rats in NASH group. The high fat diet resulted in quantitative alterations in the aerobes (E. coli) but not in the anaerobics (Lactobacill). There was an increase in the number of E. coli in the proximal small intestinal flora in NASH group than in control group. TNF-¦Áconcentration was significantly higher in NASH group than in control group. TNF-¦Áconcentration was lower in cidomycin group than in NASH group. Treatment with cidomycin showed its effect by significantly lowering serum ALT, AST and TNF-¦Álevels of NASH rats. SIBO may decrease small intestinal movement in NASH rats. SIBO may be an important pathogenesis of Nash and treatment with cidomycin by mouth can alleviate the severity of NASH.

The results of this study suggest a promising future for many NASH patients. Due to the high disease incidence of NAFLD around the world and no effective treatment at present, this case reported by Dr. Wan-Chun Wu is surely worth the attention of both doctors and the public at large.

Alternative strategy better for Crohn's Disease

Fri, 22 Feb 2008 06:52:59 PST

( from http://www.rxpgnews.com ) An international research study, published in The Lancet, has thrown into question the current method of treating Crohn’s disease – opening the door to a safer and more effective treatment option for sufferers of the chronic disease.

“Our study clearly demonstrated that this alternative treatment method was more effective at inducing disease remission than the conventional method,” said Dr. Brian Feagan, Director of Robarts Clinical Trials at Robarts Research Institute at The University of Western Ontario. Dr. Feagan coordinated the research trial and is an author on the study. “Not only were patients more likely to get their disease under control, but they were also spared exposure to steroids – the extended use of which is linked with metabolic disease and even increased mortality. It’s simply a safer, more effective treatment method.”

Called a "step-up" approach, the conventional treatment for Crohn’s disease involves first administering steroids in order to control the patient’s symptoms (abdominal pain and bloody diarrhea); the next step involves administering immune-suppressing drugs, which prepare the body to receive the third medication – an antibody that curbs the inflammatory response at the root of the disease.

The alternative strategy, called "top-down" therapy, employs early use of immune-suppressing drugs combined with an antibody in order to address the disease from the start. Symptom-treating steroids may never even be needed.

The two-year study was conducted at research centres in Belgium, Holland, and Germany and involved 129 subjects with active Crohn’s disease. 64 patients received the conventional step-up treatment and 65 the combined immune-suppressing method (top-down). 60% of the top-down subjects were symptom-free by the 26th week of the study, compared to only 36% of the step-up subjects.

“This study is a milestone in the management of Crohn’s disease,” said lead author Dr. Geert D’Haens, of the Imelda GI Clinical Research Centre at the Imelda Hospital in Bonheiden, Belgium. “It does not look at the effects of single drug intervention but at strategies to alter the natural history of this chronic destructive condition. All ‘classic’ paradigms for the management of Crohn’s disease need to be questioned.”

The impact of the study goes beyond Crohn’s disease. “We’ve seen similar results in top-down, step-up studies of rheumatoid arthritis,” said Dr. Feagan, “suggesting that the top-down approach could be the best treatment method for other chronic auto-immune diseases such as ulcerative colitis.”

May inflammatory bowel disease mimic gynecological disorders in its clinical presentation

Fri, 22 Feb 2008 05:00:00 PST

Do patients with inflammatory bowel disease receive optimal care?

Fri, 22 Feb 2008 05:00:00 PST

( from http://www.rxpgnews.com ) Inflammatory bowel disease (IBD) is a chronic recurrent gastrointestinal disease. The disease has a relatively higher morbidity in young adults, in whom growth, education, employment and wellbeing all are adversely influenced. A number of guidelines for management of inflammatory bowel disease are available for bringing evidence-based medicine into full play to improve IBD patient care. What about the actual quality of care for patients with IBD in China?

An article to be published on January 28, 2008 in the World Journal of Gastroenterology addresses this question. The research team led by Dr. Jian-Min Si from Zhejiang University, China, conducted a retrospective review of medical therapy for a hospital based-cohort of patients with IBD, involving 71 patients with Crohn's disease (CD) and 106 with ulcerative colitis (UC). Medical therapy including use of oral aminosalicylates, topical therapy, corticosteroid agents and immunomodulatory agents were analyzed.

This article reported that all the patients with ulcerative colitis received optimal doses of aminosalicylate while 39.7% patients with ileal or colonic CD were suboptimal dosed. The incidence of suboptimal dose of aminosalicylate was significantly higher in CD patients with small intestine involvement only. This phenomenon may be explained by the relatively lower incidence of CD than that of UC in China and therefore less understanding of this disease.

Another finding is that only half of the patients with active distal or left-sided ulcerative colitis received topical therapy. There is a tendency to think topical therapy is less effective in clinical practice, quite reverse to the evidence. In fact, its lower efficacy may be due to the lack of preparations, such as liquid enemas, foams, gels and suppositories, rather than due to the medication itself.

More than a quarter of patients who suffered from severe IBD did not receive oral or intravenous steroid therapy, which is possibly due to the lack of comprehensive evaluation of the patients' baseline states and re-evaluation when exacerbations occurred. In addition, the patients' and even some physicians' fear of adverse effects played a part role.

The most striking finding in this study pertains to the use of immunomodulatory drugs. Among the patients for whom immunomodulatory agents were indicated, only one fifth received these drugs. And half of the patients who received azathiopurine were suboptimal dosed in the absence of leucopenia of hepatotoxicity. The limited use of immunomodulatory drugs may be due to the lack of evidence and limited experience with these drugs in Han nationality Chinese with IBD. Uncertainty regarding the risk for neutropenia deters some physicians from using AZA at effective doses for longer periods of treatment.

The results of this study suggest the quality of care for IBD patients can be further improved. Larger prospective studies are needed to investigate the quality of care for patients with IBD and the association of the reported quality of care with patient outcomes.

University of Sydney researchers find new evidence linking kava to liver damage

Fri, 22 Feb 2008 05:00:00 PST

( from http://www.rxpgnews.com ) In recent years, serious concerns about the dangers of kava and the effects on the liver have resulted in regulatory agencies, such as the US Food and Drug Administration and Australia's Therapeutic Goods Administration, banning or restricting the sale of kava and kava products.

Originally from Fiji, where kava drinking is common, Professor Iqbal Ramzan, Dean of Pharmacy at the University of Sydney, Australia, had previously published articles on the adverse effects of kava, and wanted to investigate further the effects kava had on the liver.

His findings are published in the January 28, 2008 edition of the World Journal of Gastroenterology. Leading a team of researchers from the University of Sydney, Professor Ramzan spent one year investigating the cellular effects of kava on the liver. Kava has been used in ceremonies and for recreational and social purposes in the South Pacific since ancient times, much like alcohol, tea or coffee is in other societies today.

In the 1980s other medicinal uses for kava began to emerge and it was marketed in herbal form as a natural way to treat conditions such as anxiety, insomnia, tension and restlessness, particularly in Europe and North America.

More recently, evidence began to emerge about the adverse affect kava could have on the liver.

To test these theories, the University of Sydney study focused on the major kavalactone (the ingredient in kava believed to affect the liver) -- kavain -- and investigated the effects it had on the ultrastructure (or biological structure) of the liver.

This required the use of electron microscopes (which enable the examination of the interior of cells) provided by the Australian Key Centre for Microscopy and Microanalysis at the University of Sydney under the direction of its Deputy Director, Professor Filip Braet.

The study found that following kavain treatment the liver tissue displayed an overall change in structure, including the narrowing of blood vessels, the constriction of blood vessel passages and the retraction of the cellular lining.

Interestingly, kavain also adversely affected certain cells which function in the destruction of foreign antigens (such as bacteria and viruses), which make up part of the body's immune system.

In other words, the kavain treatment disturbed the basic structure of the liver, consequently seriously impacting the normal functioning of the liver.

The results of the University of Sydney's study clearly support earlier literature observations on kava's adverse affects on the functioning of the liver in general.

However, additional investigations into the effects of other major kavalactones on the liver, as well as studies on whether the effects of kava are reversible, are urgently needed.

A strange case of upper obstructive syndrome

Fri, 22 Feb 2008 05:00:00 PST

( from http://www.rxpgnews.com ) Aorto-duodenal fistulae (ADF) are the most frequent aorto-enteric fistulae (80%) and the most frequent presenting sign of ADF is upper gastrointestinal bleeding (UGI). A 59-year-old male patient, who underwent an aortic-bi-femoral bypass five years ago, was admitted to the Emergency Room after five days of persistent occlusive syndrome with dyspepsia and biliary vomiting. Computed tomography (CT) scan showed in the third duodenal segment the presence of an area with the characteristics of inflammatory tissue, including air bubbles between the duodenum and aortic-bi-femoral prosthesis adherent to the third duodenal portion (pcomma signq) (Figure 1). Microbiological cultures and scintigraphy were unremarkable. Esophago-gastro-duodenoscopy showed the aortic prosthesis crossing the third segment of duodenal wall occluding the intestinal lumen (Figure 2). At laparotomy, after viscerolisis, the prosthesis was detached from duodenal wall and the intestine failed to close transversely (Figure 3). To protect the intestinal wall, a pediculated fragment of the greater omentum was placed between the duodenum and aortic bypass. Furthermore, a gastrojejunal Roux anastomosis was employed. The prosthesis was not changed because there were no local or systemic signs of infection. The post-operative course was uneventful.

These findings were published in the January 21, 2008 edition of the World Journal of Gastroenterology. ADF may be primarily due to a spontaneous communication between the lumen of aortic aneurysm and intestinal loop, or secondarily due to surgical repair of aneurysms with prosthetic implants. Clinical suspicion is essential in the diagnosis of ADF and the most commonly used techniques for its diagnosis are esophago-gastro-duodenoscopy (EGDS) and CT.

Otherwise, secondary ADF is an uncommon (0.3% - 2%) and life-threatening long-term complication of aortic reconstructive surgery, with only hypothetic and speculative pathogenesis (mechanical erosion, lack of interposed retroperitoneal tissue, excessive pulsation of redundantly placed grafts, septic procedures by Staphylococcus epidermidis pbiofilmq infection, inadequate prosthetic materials).

In our case, ADF formation was related to graft pulsation on the duodenal wall.

The presentation is often subtle, with herald bleeding followed by a period of grace, or catastrophic bleeding, or rarely an episode of intestinal obstruction. The third or fourth duodenal segment is the most frequently involved site. In Dacron prosthesis patients, fistula develops in the proximal graft tract opening in the third segment of duodenum.

Because of the high mortality and morbidity associated with secondary aorto-enteric fistula, surgical treatment is always recommended. Explorative laparotomy is the treatment of choice. In the case of non-treated aortic-enteric fistula presenting with massive UGI-bleeding, the mortality rate is near 100%. Morbidity (limb loss in 10% - 40%) and mortality related to treated ADF are also high (75%) and require preventive measures, including more particularly delicate surgery and antibiotic therapy in case of infection. Several surgical procedures are possible.

ADF must be suspected whenever a patient with aortic prosthesis has digestive bleeding or unexplained obstructive syndrome. More rarely, the clinical picture of ADF is subtle, presenting as an obstructive syndrome, and in these cases the principal goal is to effectively relieve the mechanical bowel obstruction. Further study is necessary to establish the more effective diagnostic mode.

Scientists using laser light to detect potential diseases via breath samples, says new study

Mon, 18 Feb 2008 05:00:00 PST

( from http://www.rxpgnews.com ) By blasting a person's breath with laser light, scientists from the National Institute of Standards and Technology and the University of Colorado at Boulder have shown that they can detect molecules that may be markers for diseases like asthma or cancer.

While the new technique has yet to be tested in clinical trials, it may someday allow doctors to screen people for certain diseases simply by sampling their breath, according to the research team from JILA, a joint institute of NIST and CU-Boulder. This technique can give a broad picture of many different molecules in the breath all at once, said Jun Ye, a fellow of JILA and NIST who led the research.

CU-Boulder graduate research assistant Michael Thorpe, Ye, CU-Boulder doctoral student Matthew Kirchner and former CU graduate student David Balslev-Clausen describe the research in a paper that appeared in the Feb. 18 online edition of Optics Express, the free, open-access journal published by the Optical Society of America. Known as optical frequency comb spectroscopy, the technique is powerful enough to sort through all the molecules in human breath and sensitive enough to distinguish rare molecules that may be biomarkers for specific diseases, said Ye.

When breathing, people inhale a complex mixture of gases, including nitrogen, oxygen, carbon dioxide, water vapor and traces of other gases like carbon monoxide, nitrous oxide and methane, said Ye, an adjoint professor of physics at CU-Boulder. Exhaled breath contains less oxygen, more carbon dioxide and a rich collection of more than a thousand types of other molecules, most of which are present only in trace amounts.

Just as bad breath can indicate dental problems, excess methylamine may signal liver and kidney disease, ammonia may be a sign of renal failure, elevated acetone levels can indicate diabetes and nitric oxide levels can be used to diagnose asthma, Ye said.

When many breath molecules are detected simultaneously, highly reliable, disease-specific information can be collected, said Ye. Asthma, for example, can be detected much more reliably when carbonyl sulfide, carbon monoxide and hydrogen peroxide are all detected simultaneously with nitric oxide.

While current breath analysis using biomarkers is a noninvasive and low-cost procedure, approaches are limited because the equipment is either not selective enough to detect a diverse set of rare biomarkers or not sensitive enough to detect particular trace amounts of molecules exhaled in human breath, Ye said.

The new technique has the potential to be low-cost, rapid and reliable, and is sensitive enough to detect a much wider array of biomarkers all at once for a diverse set of diseases, he said.

The optical frequency comb is a very precise laser for measuring different colors, or frequencies, of light, said Ye. Each comb line, or tooth, is tuned to a distinct frequency of a particular molecule's vibration or rotation, and the entire comb covers a broad spectral range -- much like a rainbow of colors -- that can identify thousands of different molecules.

Laser light can detect and distinguish specific molecules because different molecules vibrate and rotate at certain distinct resonant frequencies that depend on their composition and structure, he said. He likened the concept to different radio stations broadcasting on separate radio frequencies.

Europe's most common genetic disease is a liver disorder

Wed, 06 Feb 2008 20:55:00 PST

( from http://www.rxpgnews.com ) Much less widely known than the dangerous consequences of iron deficiencies is the fact that too much iron can also cause problems. The exact origin of the genetic iron overload disorder hereditary hemochromatosis (HH) has remained elusive. In a joint effort, researchers from the European Molecular Biology Laboratory (EMBL) and the University of Heidelberg, Germany, have now discovered that HH is a liver disease. They report in the current issue of Cell Metabolism that the disorder develops when a crucial gene is lacking in liver cells.

Iron is essential for our body, because it is a central component of red blood cells. Too little iron can lead to dangerous anemias, but also too much iron can be detrimental as it promotes the formation of toxic radicals that lead to tissue damage. Hereditary hemochromatosis is an iron overload disorder that, affecting about one in 300 people, is probably the most common genetic disorder in Europe. Scientists have identified a gene, called HFE, that when mutated causes hemochromatosis in mice and humans. But as yet it is unknown in which tissue or organ the gene is acting to prevent iron overload.

A group of researchers around Matthias Hentze at EMBL and Martina Muckenthaler and Wolfgang Stremmel at the University of Heidelberg have now found that mice that are genetically engineered to lack HFE only in liver cells show all central features of the disease.

“For a long time scientists thought of HH as a disease of the intestine, because this is where iron uptake actually takes place,” says Matthias Hentze, Associate Director of EMBL. “Our research now reveals the crucial point is actually the liver and explains why HH patients suffer from increased iron absorption.”

HFE encodes a protein that is likely involved in transmitting signals about the current iron contents of the body to liver cells. In response to these signals, the liver cells make a special iron hormone, hepcidin that is released into the blood stream and reduces iron uptake in the intestine.

“HFE influences hepcidin expression through a series of intermediate molecules, but when the HFE gene is mutated the result is that less hepcidin is produced. This in turn means iron uptake in the intestine cannot be limited as effectively and an overload develops,” says Martina Muckenthaler, professor at the University of Heidelberg.

Camera in a pill offers cheaper, easier window on your insides

Thu, 24 Jan 2008 05:00:00 PST

( from http://www.rxpgnews.com ) What if swallowing a pill with a camera could detect the earliest signs of cancer? The tiny camera is designed to take high-quality, color pictures in confined spaces. Such a device could find warning signs of esophageal cancer, the fastest growing cancer in the United States.

A fundamentally new design has created a smaller endoscope that is more comfortable for the patient and cheaper to use than current technology. Its first use on a human, scanning for early signs of esophageal cancer, will be reported in an upcoming issue of IEEE Transactions on Biomedical Engineering.

Our technology is completely different from what's available now. This could be the foundation for the future of endoscopy, said lead author Eric Seibel, a University of Washington research associate professor of mechanical engineering.

In the past 30 years diagnoses of esophageal cancer have more than tripled. The esophagus is the section of digestive tract that moves food from the throat down to the stomach. Esophageal cancer often follows a condition called Barrett's esophagus, a noticeable change in the esophageal lining. Patients with Barrett's esophagus can be healed, avoiding the deadly esophageal cancer. But because internal scans are expensive most people don't find out they have the condition until it's progressed to cancer, and by that stage the survival rate is less than 15 percent.

These are needless deaths, Seibel said. Any screen that detected whether you had a treatable condition before it had turned into cancer would save lives.

An endoscope is a flexible camera that travels into the body's cavities to directly investigate the digestive tract, colon or throat. Most of today's endoscopes capture the image using a traditional approach where each part of the camera captures a different section of the image. These tools are long, flexible cords about 9 mm wide, about the width of a human fingernail. Because the cord is so wide patients must be sedated during the scan.

The scanning endoscope developed at the UW is fundamentally different. It consists of just a single optical fiber for illumination and six fibers for collecting light, all encased in a pill. Seibel acted as the human volunteer in the first test of the UW device. He reports that it felt like swallowing a regular pill, and the tether, which is 1.4 mm wide, did not bother him.

Once swallowed, an electric current flowing through the UW endoscope causes the fiber to bounce back and forth so that its lone electronic eye sees the whole scene, one pixel at a time. At the same time the fiber spins and its tip projects red, green and blue laser light. The image processing then combines all this information to create a two-dimensional color picture.

In the tested model the fiber swings 5,000 times per second, creating 15 color pictures per second. The resolution is better than 100 microns, or more than 500 lines per inch. Although conventional endoscopes produce images at higher resolution, the tethered-capsule endoscope is designed specifically for low-cost screening.

Using the scanning device is cheap because it's so small it doesn't require anesthesia and sedation, which increase the cost of the traditional procedure.

The procedure is so easy I could imagine it being done in a shopping mall, Seibel said.

A wireless scope manufactured by a different group, originally designed to pass through the body and detect intestinal cancer, is now being marketed for esophageal cancer screening. The competing technology comes in a pill about the width of an adult fingernail and twice as long. By contrast, the UW's scanning fiber endoscope's dimensions are about half as big and the device fits inside a standard pill capsule. The pill could be even smaller, Seibel said, but the researchers chose a size that would be easy to handle and swallow.

Another disadvantage of wireless capsules is they only allow a single fly-by view.

You have no control over the other pill once it's swallowed. It just flutters down, Seibel said. But since the UW scope is tethered, the doctor can move it up and down along the region of interest.

Only a small percentage of people who get Barrett's esophagus, about 5 percent to 10 percent, develop cancer. So any screening method must have a low price to be cost-effective.

The next big challenge is to make this cheaply, Seibel said. The researchers are negotiating a contract to commercialize the technology. In the future they hope to not only take pictures, but also deliver treatments through the device, and to apply it to other diseases.

Ginsenosaide Rb1 (R1)- chinese medicine ingredient found to protect liver

Wed, 16 Jan 2008 13:48:31 PST

( from http://www.rxpgnews.com ) Many patients worldwide are going to receive major abdomen surgery or intestine transplantation every year and expect to be afflicted with liver injury afterwards. The finding of a research group headed by Professor Han Jing-Yan in China and reported in January 7, 2008 of the World Journal of Gastroenterology (volume 14, issue 1) may prove good news for them.

The study by Han Jing-Yan et al discovered Ginsenosaide Rb1 (R1) is able to prevent hepatic microcirculatory disturbance and subsequent liver injury in mice induced by intestine ischemia and reperfusion (I/R). R1 is one of the major effective ingredients of Panax notoginseng (PN), a traditional Chinese herb medicine frequently included in various compound Chinese medicines for treatment of liver injury and numerous other diseases in China and other Asian countries.

In 2005, Dr. Han was working on the effect and underlying mechanism of cardiotonic pills (CP) in cooperation with Prof. Toshifumi Hibi and Dr Yoshinori Horie in the Department of Internal Medicine, School of Medicine, Keio University, Japan. They revealed the beneficial effect of CP for improving gut I/R induced liver injury (Horie Y, Han JY, Mori S, Konishi M, Kajihara M, Kaneko T, Yamagishi Y, Kato S, Ishii H, Toshifumi Hibi. Herbal cardiotonic pills prevent gut ischemia/reperfusion-induced hepatic microvascular dysfunction in rats fed ethanol chronically. World J Gastroenterol 2005; 11(4): 511-515). However, CP is a compound Chinese medicine preparation that contains PN, and salvia miltiorrhiza and Borneol additionally. It was not clear at that time which one among the three ingredients is actually responsible for this action. The present report of Dr. Han¡¯s group shows R1, one of the major compounds of PN, protects against the gut I/R induced liver injury impressively.

In this study, the animal model is established by ligation of the superior mesenteric artery (SMA) in C57/BL mice for 15 min followed by 30 min reperfusion. The researchers apply several techniques to address the issue concerned. First, they take advantage of an inverted intravital microscope assisted by a 3CCD color camera and high speed video camera and laser confocal microscope. This enables a dynamic examination of the hepatic microcirculatory parameters under investigation in mouse subjected to gut I/R and observes the gut I/R imposed impairment in vascular diameter, red blood cell velocity, sinusoid perfusion and leukocyte rolling and adhesion is obviously alleviated or completely abolished by pretreatment with R1.

Secondly, immunofluorescent staining is used to examine the endothelial adhesion molecules E-selectin and ICAM-1. Finally, blood is collected for detecting the expression of adhesion molecules in leukocyte and the activity of hepatic enzymes, including LDH, ALT, and AST, and the concentration of pro-inflammatory mediators such as TNF-¦Á, IL-6 and monocyte chemotactic protein-1 (MCP-1). After careful evaluation, the researchers concluded R1 prevents I/R-induced hepatic microcirculation disturbance and hepatocyte injury by inhibition of leukocyte rolling and adhesion, through depressing the expression of E-selectin in endothelium and CD18 in neutrophils. This result is of significance not only for better understanding the mechanism of the effect of PN and PN containing preparations, but also for R1 to be used to prevent liver injury originated from gut I/R.

Indian medicinal plant Acanthus ilicifolius may combat liver cancer

Wed, 16 Jan 2008 05:00:00 PST

( from http://www.rxpgnews.com ) Liver cancer is the fifth most common cancer in the world with a poor prognosis. About three quarters of the cases of liver cancer are found in Southeast Asia, including China, Hong Kong, Taiwan, Korea, India, and Japan. The frequency of liver cancer in Southeast Asia and sub-Saharan Africa is greater than 20 cases per 100,000 population. Moreover, recent data show the frequency of liver cancer in the U.S. overall is rising.

With the increasing trend in the incidence of cancers in our country, biomedical research directed at early detection and diagnosis, prognosis and survival, as well as prevention of progression of malignancy, is of prime importance. The aim of cancer chemoprevention is to circumvent the development and progression of malignant cells through the use of non-cytotoxic nutrients, herbal preparations/natural plant products, and/or pharmacological agents. Encouraging dietary intake with herbal supplements may therefore be an effective strategy to limit DNA lesions and organic injuries leading to cancers and other chronic degenerative diseases. A research article published in the December 28 issue of the World Journal of Gastroenterology explores this point.

A research article published on December 28, 2007 in the World Journal of Gastroenterology (volume 13, issue 48) addresses this problem. The research team led by Prof. Malay Chatterjee from Jadavpur University investigated the primary chemopreventive mechanisms of Acanthus ilicifolius in an in vivo tumor-transplanted murine model. A. ilicifolius, popularly known as pHarkach Kantaq is distributed widely throughout the mangroves of India, including Sunderbans in West Bengal, west coasts, and the Andamans, and in other Asian countries like Singhal, Burma, China, Thailand etc.

The results showed the aqueous leaf extract (ALE) of the plant was substantially effective in preventing hepatic DNA alterations and sister-chromatid exchanges (a type of chromosomal damage) in tumor-bearing mice. The study further demonstrated that ALE treatment was able to limit liver metallothionein expression, a potential marker for cell proliferation, and lengthen the mean survival of animals to a significant extent. The findings suggest that A. ilicifolius may be used as a potential chemoprotector against hepatic neoplasia.

This research from Prof. Chatterjeeos laboratory opens up a promising avenue in cancer chemoprevention with the use of indigenous plants. The results obtained from this in vivo study seem interesting and encouraging. Lack of toxicity favors further preclinical evaluation of A. ilicifolius in a defined chemical carcinogenesis model. Elucidation of its anticarcinogenic mechanisms of action at the intricate molecular circuits, and isolation and characterization of its active principles, will provide a better understanding of the anti-cancer/chemoprevention strategy of A. ilicifolius. If these studies are found to be really functional, we will have the beginning of a new chemoprevention program with herbal supplements that could have the broadest implications for the well-being of society.

Eltrombopag effective for hepatitis C patients with low blood-platelet counts

Fri, 28 Dec 2007 05:00:00 PST

( from http://www.rxpgnews.com ) NEW YORK (Dec. 28, 2007) -- For patients with hepatitis C, having a low blood platelet count is a frequent complication associated with advanced disease. This problem is compounded by the fact that standard antiviral treatment for the disease can further reduce platelet numbers to dangerously low levels, effectively denying these patients the treatment they urgently need. Now, research published in the New England Journal of Medicine finds that a new drug, eltrombopag, appears to significantly boost platelet counts, opening the door to effective treatment.

In this study, eltrombopag increased platelet counts in a dose-dependent manner, allowing more patients to complete the first 12 weeks of antiviral therapy -- an important treatment goal, says Dr. Samuel Sigal, who led the study at NewYork-Presbyterian Hospital/Weill Cornell Medical Center in New York City -- one of 22 study sites.

Dr. Sigal is assistant professor of medicine in the Division of Gastroenterology and Hepatology at Weill Cornell Medical College and assistant attending hepatologist in the Center for Liver Diseases and Transplantation at NewYork-Presbyterian/Weill Cornell.

The Phase 2 placebo-controlled study followed 74 patients with low platelet counts and cirrhosis of the liver due to hepatitis C virus (HCV) infection. Seventy-four percent of those randomized to take the lowest dose (30 milligrams daily) saw their platelet counts go up significantly, while 79 percent and 95 percent of the participants saw increases with the higher doses (50 or 75 milligrams daily, respectively). And, 12 weeks of antiviral therapy were completed by 36, 53 and 65 percent of patients at the three dose levels -- with increased numbers matched to the size of the dose. Underlining the trend, less than a quarter of patients receiving placebo completed their therapy.

The study identified side effects -- including headaches, dry mouth, abdominal pain and nausea. None were serious enough to discontinue the therapy.

It's estimated that 4 million people in the U.S. and 170 million worldwide carry the hepatitis C virus. HCV is transmitted primarily by blood and blood products. The majority of infected individuals have either received blood transfusions prior to 1990 (when screening of the blood supply for HCV was implemented) or have used intravenous drugs. More rarely, it can also be transmitted through sexual intercourse and perinatally (mother to baby).

The virus causes inflammation and scarring in the liver, and while it is curable in about half of those who have it, it can lead to significant liver damage, liver cancer and death in others. HCV infection is a common cause of cirrhosis and the most common reason for a liver transplant.

With other eltrombopag findings, NewYork-Presbyterian/Weill Cornell's Dr. James Bussel led research, also reported in the New England Journal of Medicine, finding the platelet growth factor successfully increased platelet counts and decreased bleeding in patients with Immune Thrombocytopenic Purpura (ITP), an autoimmune disease that dramatically reduces the number of platelets in their blood. (Dr. Bussel is an Advisory Board Member for GlaxoSmithKline; has received research grant support, lecture fees, and consulting fees from GlaxoSmithKline; and reports equity ownership in the company.)

The current study was sponsored by GlaxoSmithKline, which is developing eltrombopag. Eltrombopag (marketed as Promacta in the U.S. and Revolade in Europe) is an investigational oral, non-peptide platelet growth factor that induces the proliferation and differentiation of cells to produce platelets. While other drugs that restore normal platelet functions are infusions or injections, eltrombopag is a once-a-day pill.

Breath test can discriminate between a bacterial overgrowth and IBS

Wed, 19 Dec 2007 05:00:00 PST

( from http://www.rxpgnews.com ) The gastrointestinal (GI) tract is colonized by bacteria immediately after birth; Escherichia coli, Streptococci and Clostridi are the first bacteria harboured by the colon, followed by anaerobic Enterococci, Lattobacilli and Bacteroidi. These commensal bacteria inhabiting the human intestine (i.e., intestinal microflora) participate in the development and maintenance of gut sensory and motor functions, including the promotion of intestinal propulsive activity; on the other hand, intestinal motility represents one of the major control systems of gut microflora, though the sweeping of excessive bacteria from the lumen. There is emerging evidence indicating that changes in this bi-directional interplay contribute to the pathogenesis of gut diseases, such as small intestinal bacterial overgrowth (SIBO).

Many factors affect the type and distribution of the bacteria along the GI tract, starting from the type of delivery and nursing in the first days of life, up to the food habits during the adult life: a SIBO is often present in adult population of westernized countries, because of poor daily intake of fibres and faecal stasis; such an overgrowth contributes to a chronic inflammation on intestinal mucosa and development of symptoms, such as abdominal pain, diarrhoea or stipsis.

These symptoms look like those of inflammatory bowel diseases (IBS) and, unfortunately, most of these patients with a bacterial overgrowth are inappropriately treated with topically-active non-steroidal anti-inflammatory agents. In fact, these compounds have no antibacterial activity and, therefore, they do not remove the causative factors of the symptoms (bacterial overgrowth) and are likely to provoke even severe adverse events.

The breath test is a recently developed test, which is able to detect elevated concentrations of hydrogen in the expired air. In presence of a SIBO, dietary carbohydrates are metabolised with production of massive amounts of hydrogen that are eliminated with the breath. Thus, the breath test consists in administering 50-75 grams of lactulose and assaying the concentrations of hydrogen in the expired air; if these concentrations exceed 10 to 20 part per million, the subject is suspected to have a SIBO and should be appropriately treated with antibiotics.

Clinicians should be encouraged to perform a breath test to promptly identify a bacterial overgrowth, because the disorder has several systemic consequences ranging from malabsorption of lipids and liposoluble vitamins and loss of electrolytes, to a more severe translocation of bacteria (usually, gram-negative and aerobic bacteria, such as Escherichia, Proteus, Enterobacter and Klebsiella) from the GI tract to extraintestinal tissues; all these factors may lead to sepsis and multiorgan failure.

Today, there is an effective treatment for bacterial overgrowth, which is rapidly corrected by the use of locally acting non-absorbable antibiotics, such as rifaximin polimorph A, which reverses the process (intestinal bacterial overgrowth) and prevents the cascade of events leading from intestinal low-grade inflammation to symptom development.

Who is the arch-criminal in the development of hepatopulmonary syndrome?

Wed, 19 Dec 2007 05:00:00 PST

( from http://www.rxpgnews.com ) The hepatopulmonary syndrome (HPS) develops when an arterial oxygenation deficiency occurs due to intra-pulmonary vascular dilatations that are often associated with severe hepatic disease. HPS occurs in 15-20% of patients with liver cirrhosis undergoing evaluation for orthotopic liver transplantation. Recent studies support that the presence of HPS significantly increases mortality in cirrhosis, particularly in those with decompensated liver disease.

One of the characteristics of HPS is intra-pulmonary vascular dilatation. The intra-pulmonary vascular dilatation severely affects pulmonary gas exchange, and consequently leads to hypoxia and raised mortality of cirrhotic patients. The present research hotspots focus mainly on clarifying the pathogenesis of HPS, particularly in exploring the mechanism of intra-pulmonary vascular dilatation.

Dr. Hui-Ying Zhang et al. developed a rat model characteristic of cirrhosis and HPS that can be non-invasively induced by multiple pathogenic factors including high fat diet, alcohol, cholesterol, corn flour and CCl4 and demonstrated a significantly increased level of lipopolysaccharide (LPS) in plasma is closely related to the decreased blood oxygen content and intra-pulmonary vascular dilatation. And they further characterized the relation between the progeression and severity of HPS and the degree of hepatic dysfunction, and explored how intestinal endotoxemia (IETM) affects the intra-pulmonary vascular dilatation.

In the research, Dr. Zhang et al. dynamically observed typical histological changes in both liver and lung and found that the progression and severity of HPS were closely associated with increased plasma LPS level, and that there was a paralleling deterioration between the lung function and the hepatic function in the cirrhotic rats. This indicated that HPS is interrelated with underlying liver disease and supported their hypothesis that hepatic pathological alteration is a substantial basis for the development of HPS in cirrhotic rats.

On the other hand , they also observed and found that dynamic alterations of plasma endotoxin were closely associated with increased expression of eNOS, iNOS, HO-1 and increased number of capillaries, which demonstrated that eNOS, iNOS and HO-1 were involved in increased NO and CO production in the lung. The elevated NO resulted preferably from iNOS of pulmonary macrophages and, to a lesser extent, from eNOS in the lung of cirrhotic rats. Both NO and CO are involved in pulmonary vascular abnormalities, and pulmonary macrophages play a role to HPS. They also found that the exhibition of pulmonary vascular abnormalities was not only in vascular dilatation but also in increased number. The results suggest that both NOS/NO and HO-1/CO pathways are contributor to the development of HPS, and that IETM plays a leading role in the development of HPS in the cirrhotic rats.

More interesting, they observed and found a mutual inhibition between NOS/NO and HO-1/CO pathways by using respective inhibitors, and consequently demonstrated that NOS/NO and HO-1/CO pathways may be interrelated in pathogenesis of intra-pulmonary vascular abnormalities in the development of HPS.

In conclusion, it is IETM that is the arch-criminal in the development of hepatopulmonary syndrome. Therefore, the strategy directed against LPS will certainly be effective in the prevention and treatment of HPS.

Research reveals secrets of alcohol's effect on brain cells

Fri, 07 Dec 2007 05:00:00 PST

( from http://www.rxpgnews.com ) NEW YORK (Dec. 7, 2007) -- Alcohol triggers the activation of a variety of genes that can influence the health and activity of brain cells, and new research from Weill Cornell Medical College in New York City sheds light on how that process occurs.

The findings, published in the Nov. 21 issue of The Journal of Neuroscience, may also edge scientists closer to understanding alcohol-linked disorders such as the brain damage associated with chronic alcoholism, and the abnormal brain development seen in the fetal alcohol syndrome (FAS).

If you are going to understand the biological effects of alcohol on genes within cells, you have to understand the molecular machinery driving the transcription, or activation, of the genes in question. That's what we believe we have done here, says the study's senior author Dr. Neil L. Harrison, professor of pharmacology and pharmacology in anesthesiology at Weill Cornell.

In research conducted in cell cultures and in mouse neurons in vivo, his team found that alcohol stimulates a ubiquitous, stress-linked biochemical cascade -- called the heat shock pathway -- to send a molecule called heat shock factor 1 (HSF1) into the neuron's nucleus. HSF1 then stimulates the transcription of many of the genes known to be activated by alcohol.

The fact that alcohol triggers the activation of genes in the brain is not new and has long been the subject of intense research.

One gene in particular, called Gabra4, is closely linked to the function (or dysfunction) of receptors for GABA, an important neurotransmitter.

We knew that levels of expression of Gabra4 fluctuated rapidly in the presence of alcohol, and so we wondered if we could find out how this happens, says lead author Dr. Leonardo Pignataro, instructor in pharmacology in anesthesiology at Weill Cornell.

At the same time, research in Korea with the C. elegans worm (a common tool for genomics research) had discovered that alcohol worked on a particular bit of DNA to trigger activity in the heat shock pathway, finding the same piece of DNA in the Gabra4 gene of mice and humans. This was all very intriguing, because the heat shock pathway is a biochemical mechanism found in almost all cells and all organisms, says Dr. Harrison. Scientists believe it helps cells deal with stressors -- including excessive heat or environmental toxins -- substances such as alcohol.

Working with mouse cells in the lab, the researchers used microarray technologies to search for genes other than Gabra4 that might be activated when the heat shock pathway was exposed to alcohol. They found many others.

The big question that remains is how does this activation occur The current theory holds that, under conditions of stress, heat shock proteins break away from a key molecule, HSF1. HSF1 then makes its way to the cell nucleus, where it helps stimulate the transcription and activation of a variety of genes that enable the cell to survive stress. We think this may happen with alcohol exposure, Dr. Harrison explains.

This finding, observed in vitro in the cell cultures, was replicated in in vivo experiments in mice, conducted in the lab of Dr. Daniel Herrera, assistant professor of psychiatry at Weill Cornell and an attending psychiatrist at NewYork-Presbyterian/Weill Cornell.

It was really exciting to see this mechanism work itself out in an animal model, suggesting that this same pathway may mediate at least some of the effects of alcohol on human brain cells, Dr. Herrera says.

Exactly what those effects might mean clinically remains in the realm of speculation for now, the researchers stress.

Alcohol can have bad effects -- the well-known effects of alcoholism, such as liver or brain damage, for example -- but moderate alcohol use also has more benign effects, such as the improvement in cardiovascular health observed in drinkers of red wine compared with tee-totallers, Dr. Pignataro points out.

One theory holds that alcohol-mediated stimulation of the heat shock pathway might trigger genes that help mop up mis-folded proteins that can damage cells. This would be a beneficial effect.

But it might also be possible that inappropriate activity of this pathway -- either during fetal brain development or in the adult brain -- is harmful. We just don't know, Dr. Harrison says. We'd certainly like to explore these issues going forward, and this research will give us some tools to answer these questions.

The most important candidate genes for pancreatic stone formation

Tue, 13 Nov 2007 05:00:00 PST

( from http://www.rxpgnews.com ) Stone formation is an important feature of chronic pancreatitis, especially tropical calcific pancreatitis (TCP), where the stones are large in size, highly irregular in shape and cause enormous tissue destruction. The exact mechanism of stone formation is not well-understood. It is very important to understand the initial event so that stone formation can be controlled before it causes obstruction and damage to the pancreatic tissue. One such study was recently reported in the November 28 issue of the World Journal of Gastroenterology because of its significance in pancreatic diseases.

In an attempt to understand the initiating event in stone formation in chronic pancreatitis, Dr. Chandak and his group initiated this study. Protein plug formation is an important primary event in the final stone formation and hence some proteins must be increased in their concentration in the pancreatic juice. Lithostathine (encoded by reg1 gene) has been isolated as a major protein component from stones of alcoholic chronic pancreatitis patients, and has been found to be 2 to 3 times less abundant in the pancreatic juice of chronic pancreatitis patients than in controls. Although the exact function of reg1 protein is not clear, it has been proposed to regulate the process of stone formation.

The team proposed that mutations in the promoter region of reg1 could lead to altered levels of the protein, or that the gene variants could predispose the reg1 protein to increased cleavage by trypsin and form fibrils that may precipitate and obstruct the duct by forming protein plugs and calculi. The interaction between pancreatic inflammation and stone formation in chronic pancreatitis is also not well understood; this study also investigated the interaction between the reg1 gene and the established susceptibility genes for TCP, such as pancreatic secretory trypsin inhibitor and cathepsin B (encoded by SPINK1 and CTSB respectively).

On testing the hypothesis in a large cohort of ethnically matched TCP patients and normal individuals, Dr. Chandak and his group discovered that mutations in reg1, including those in the regulatory region either independently or in the presence of known mutations in SPINK1 and/or CTSB, might not be a cause of stone formation in TCP patients. This opens up scope for further research on alternative mechanisms, such as calcium signaling and regulation in stone formation in chronic pancreatitis.

The observations made by this study thus contribute significantly by ruling out the role of one of the most important candidate genes for pancreatic stone formation.

Antegrade bowel intussusception can cause recurrent, chronic postoperative intestinal obstruction

Tue, 13 Nov 2007 05:00:00 PST

( from http://www.rxpgnews.com ) Several complications can be seen after pancreatic surgery, most notably bleeding, infections and anastomotic dehiscence. Bowel obstruction can also be seen due to internal hernias or anastomotic strictures. A more unusual etiology for bowel obstruction in this setting is intussusception.

Intussusception is often a pediatric condition. Adult cases have rarely been reported, and are usually caused by a lead point. The paper published by Dr. Luis Leonos group on the November 28 issue of World Journal of Gastroenterology describes a rare case of adult intussusception without lead points. Cases without lead points are most often seen after gastric bypasses for morbid obesity or after biliary reconstruction for choledochal cysts. Intussusception occurring after pancreatic duct reconstructions is rare. The report represents the second report in the literature of such an occurrence.

This patient was quite a challenge for surgeons at the University of Arizona. She was a middle-aged female who presented with abdominal pain and vomiting of 24-hour duration. Her history was significant for pancreas divisum and chronic pancreatitis. Four years prior, she underwent a Whipple procedure as therapy for her pancreatic abnormalities. The indications to perform a Whipple procedure to correct pancreas divisum are questioned by the authors in their paper. She required revision one year later with a Puestow operation due to stricture of the pancreatico-intestinal anastomosis. Ever since, she had been experiencing intermittent abdominal pain for which she had been prescribed strong pain killers, with only partial relief. Upon arrival at the University of Arizona, severe tenderness to abdominal palpation was elicited. Emergent surgical intervention was deemed necessary. An intussusception just distal to the most distal Roux-en-Y connection was found, causing two loops of dilated small bowel up to 10-cm in maximal diameter, and also about 1 foot of non-perforated necrotic small bowel. The intussusception was antegrade, obstructing both Roux-en-Y reconstructions. No lead point lesions were seen. The intussuscepted intestine was reduced, the necrotic bowel resected, and a side-to-side anastomosis between the most distal aspect of the bowel and the Roux-en-Y reconstruction that was directed towards the Puestow procedure was performed. She was subsequently discharged without complications.

The chronic nature and severity of this patientos symptoms made her diagnosis very challenging. Previously performed CT scans showed findings that, in retrospect, suggest transient short bowel segment intussusceptions. The authors postulate that this complication may be a severe variant of Roux-en-Y stasis syndrome. The myoelectric activity of the Roux limb is often dysfunctional, split and retrograde and of high amplitude. It is possible that the intussusception seen in this patient was the result of severe disruption of the intestinal pacemaker activity, which is even more likely in the absence of lead points.

Antegrade intussusception after pancreatic surgery is extremely rare. This report by Dr. Leonos group is the second such occurrence. Their patient had previous episodes of abdominal pain and vomiting, which suggests that altered intestinal motility may have contributed to her presentation. Intussusception should always be considered in cases of bowel obstruction in adults after pancreatic reconstructions.

Hepatitis C treatment reduces the virus but serious liver problems may progress

Tue, 06 Nov 2007 05:00:00 PST

( from http://www.rxpgnews.com ) Patients with chronic hepatitis C and advanced liver disease who did not respond to previous standard therapy experienced significant decreases in their liver enzymes, viral levels, and liver inflammation following treatment with long-term pegylated interferon. However, the treatment did not slow or prevent the progression of serious liver disease. These findings come from the clinical trial, Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) and were reported at the annual meeting of the American Association for the Study of Liver Disease in Boston on November 5, 2007. HALT-C is funded by the National Institutes of Health (NIH) with additional support from Hoffmann-La Roche Inc.

The HALT-C trial unequivocally demonstrated that maintenance therapy with peginterferon does not prevent progression of liver disease among patients who have failed prior treatments, said James Everhart, M.D., project scientist for HALT-C and a program director for the Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the principal sponsor of HALT-C at NIH. These results add to the incentive to develop more effective drugs that will benefit patients with severe liver disease due to hepatitis C.

HALT-C, a randomized multicenter trial of 1,050 patients with chronic hepatitis C who had failed prior treatment to eradicate the infection, assessed whether long-term treatment with peginterferon alfa-2a reduced the development of cirrhosis, liver failure, or liver cancer. The 517 patients randomized to the treatment arm received 90 micrograms of peginterferon in weekly injections for 3.5 years. The 533 patients in the control arm underwent the same follow-up and care as the treated patients including liver biopsies, quarterly clinic visits, and blood tests. All patients had advanced liver fibrosis, a gradual scarring of the liver that puts patients at risk for progressive liver disease.

The outcomes assessed in HALT-C were death, liver cancer, ascites (excess fluid in the abdomen), or encephalopathy (brain and nervous system damage), and for those who did not have cirrhosis initially, the development of cirrhosis. At the end of the study, 34.1 percent of the patients in the treated group and 33.8 percent of the patients in the control group had experienced at least one outcome. Patients in the treated group had significantly lower blood levels of the hepatitis C virus and less liver inflammation. However, there was no major difference in rates of any of the primary outcomes between groups.

Among treated patients, 17 percent stopped peginterferon by one year and six months and 30 percent stopped the drug two years later. Adverse events such as infections, musculoskeletal or digestive problems were the most common reasons patients stopped taking the drug.

Viral hepatitis C infects more than 100 million persons worldwide and as many as 4 million persons in the United States. Hepatitis C ranks with alcohol abuse as the most common cause of chronic liver disease and leads to about 1,000 liver transplants in the United States each year. The best current antiviral therapy consists of pegylated interferon given by injection in combination with oral ribavirin prescribed for about 6 months to a year. This therapy eliminates the virus in about 50 percent of infected patients.

Endosonography-guided biliary drainage is useful in cases with failed endoscopic biliary stenting

Fri, 02 Nov 2007 04:00:00 PST

( from http://www.rxpgnews.com ) The role of endosonography (ES) in digestive diseases is expanding gradually from diagnostic applications to therapeutic ones. The feasibility of ES-guided cholangiopancreatography was first reported by Harada et al. (pancreatography) and Wiersema et al. (cholangiography) in 1995 and 1996, respectively. Several reports on the application of ESBD for a therapeutic purpose have been published since 2001. However, there have been no reports as to the influence of this technique on the gut wall, the bile duct, and the intervening tissues. A research article published on November 7 issue 41 of World Journal of Gastroenterology addresses one answer to this question in a case report form.

Dr. Fujita and his colleagues from Sendai City Medical Center applied ESBD via the duodenum for decompression of the biliary tree, in a patient with cancer of the papilla of Vater complaining of itching and jaundice, and reported the results of histological evaluation on and around the sinus tract created by ESBD. The patient underwent pancreaticoduodenectomy 14 days after ESBD. Macroscopically, the sites of puncture in the bile duct and the duodenum were clear without infection, hemorrhage, or hematoma. Histological examination revealed mild inflammatory cell infiltrate adjacent to the sinus tract in the duodenal wall and the bile duct wall without hemorrhage. A fistula was formed along the tract of the puncture without significant reactive changes. This is the first report describing the histological condition of the sinus tract established by this method.

They concluded these results were attributable to the use of endosonography as a guide, resulting in a low potential risk of major bleeding as color Doppler evaluation was utilized for determination of the route of puncture. Injury of adjacent organs was also minimized due to clear visualization of the structures in the area of interest. The method of choice for biliary obstruction is, in general, endoscopic biliary stenting. At present, percutaneous transhepatic cholangio-drainage (PTCD) is considered to be a substitute. PTCD, however, is followed by pain after placement of a drainage tube and restricts patients' daily living. On the contrary, ESBD is a safe and effective method of biliary drainage without pain or restriction in daily living, as in endoscopic biliary stenting, and will therefore replace PTCD in a large proportion of patients having an obstructed biliary tree with difficult cannulation of the bile duct, duodenal stenosis, and deformity of the papilla by cancer, which hinder detection of the orifice, regardless of the likelihood of successful PTCD.

The research team also predict further development of accessory devices specialized for ESBD will expand its indications. ESBD may replace PTCD, or even EBS, in selected patients, although further comparative study is needed.

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Reference: Fujita N, Noda Y, Kobayashi G, Ito K, Obana T, Horaguchi J, Takasawa O, Nakahara K.Histological changes at an endosonography-guided biliary drainage site: A case report. World J Gastroenterol 2007; 13(41): 5512-5515

24-week course of interferon-alpha therapy prolongs survival in patients hepatitis C virus

Fri, 02 Nov 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Patients with the hepatitis C virus (HCV) have a risk of frequent recurrence and deterioration of liver function, even after curative treatment for the primary hepatocellular carcinoma (HCC). This unfavorable prognosis is associated with a sustained HCV infection. Thus, both the prevention of HCC recurrence and the preservation of liver function are high priorities when trying to improve the prognosis of patients with HCV-related HCC. Antiviral therapy for chronic hepatitis C (HCV) after treatment for primary HCC is the essential factor required for an improved prognosis.

A research article written by a study group at Japan's Hiroshima University Hospital, published on October 28 in the World Journal of Gastroenterology, suggests the importance of viral eradication. This study group performed a matched case-controlled study and compared 42 patients undergoing a 24-week course of interferon therapy and 42 patients who did not receive any interferon therapy. The purpose of the study was to determine whether a 24-week course of interferon-alpha therapy after curative treatment for HCV-associated HCC could possibly influence tumor recurrence, patient survival, and liver function.

The study group found that the second recurrence rate was significantly lower in patients that underwent interferon therapy as compared to those patients that did not have interferon therapy, although the first recurrence rate in patients with and without interferon therapy did not differ. Additionally, results also indicated that the interferon therapy patients had longer survival periods than the patients who did not have interferon therapy.

The study group also determined that when patients without interferon therapy were compared to patients without any virological response, only the virological responders within the interferon therapy group had a better prognosis with regard to the recurrence, liver function, and survival. Overall, the results indicated it is the sustained virological response that is the most important factor for decreasing the risk of HCC recurrence, including for the second recurrence and for prolonged survival. The state of the virological response improved the prognosis by suppressing the multicentric recurrence, which was related to the sustained hepatic necrosis and inflammation.

The study group also demonstrated that the state of the sustained virological response was responsible for preventing functional liver deterioration, which is related to the underlying HCV-related hepatic damage. Thus, patients with viral elimination are able to survive longer than both the patients without interferon therapy and the patients without virological response following interferon therapy, due to the decreased HCC recurrence and preservation of hepatic function.

After curative treatment of primary HCC, a 24-week course of interferon therapy should be recommended for the purpose of viral eradication.

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Reference: Jeong SC, Aikata H, Katamura Y, Azakami T, Kawaoka T, Saneto H, Uka K, Mori N, Takaki S, Kodama H, Waki K, Imamura M, Shirakawa H, Kawakami Y, Takahashi S, Chayama K.Effects of a 24-week course of interferon-alpha therapy after curative treatment of hepatitis C virus-associated hepatocellular carcinoma. World J Gastroenterol 2007; 13(40): 5343-5350

Does neural cell adhesion molecule-180 predict survival in colorectal cancer?

Fri, 02 Nov 2007 04:00:00 PST

( from http://www.rxpgnews.com ) When a person learns they are suffering from cancer, the first question in their mind is always: How much time do I have? Unfortunately, this is a question to which the researchers have long been seeking an absolute answer. Tumor progression to local invasion and metastasis are the most relevant processes for prognosis, and predictive factors for survival are sometimes the only hope for cancer patients. Tumor suppressors and adhesion molecules represent one of the primary challenges in cancer therapy.

NCAM is an embryologic adhesion molecule suggested to be a significant factor for survival in patients with various solid tumors. A correlation between reduced NCAM expression and poor prognosis has been reported for some cancer types. The existence of NCAM-180 has been proposed to function as a tumor suppressor in colon carcinoma. However, no prospective research has yet been conducted to evaluate the prognostic value and the frequency of NCAM-180 in colorectal cancer. Yet cancer patients and their families obviously want to know if they can recover from this miserable disease or what they may experience during its clinical course.

A research article published on November 7 in the World Journal of Gastroenterology addresses this question. The research team, led by Dr. Tascilar from Zonguldak Karaelmas University, investigated the frequency of NCAM-180 expression and the effect of its existence on clinical course in 26 patients suffering from colorectal cancer over a period of 4 years.

One conclusion reported by the investigators is that NCAM-180 expression was determined in only one patient with stage II cancer, with an uneventful clinical course during a follow-up period of 30 months. However, the overall rate was only 3.84%, and statistical correlation analysis of survival with NCAM-180 expression was not possible due to this low frequency.

Another interesting conclusion is that a comparison according to tumor differentiation and stage revealed that loss of NCAM-180 expression, in either well-differentiated or stage II cancer, did not result in a worse clinical course in other patients.

The authors conceded that as a consequence of the limited number of cases in their series, it might not be possible to make a generalization. Nevertheless, routine use of NCAM-180 expression as a prognostic marker for colorectal carcinoma does not seem feasible or cost-effective in clinical practice, due to it being present at a very low frequency.

The most critical deficit in the ability to treat cancer effectively is the lack of knowledge about cellular basis and markers for early diagnosis. The verification of an association between various types of malignancies and adhesion molecules might provide new targets in cancer therapy by indicating the accurate goals. Further studies with a greater number of cases are thus called for, to study the underlying mechanisms of tumor metastasis and prognosis in colorectal carcinoma.

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Reference: Tascilar O, Cakmak GK, Tekin IO, Emre AU, Ucan BH, Irkorucu O, Karakaya K, Gul M, Engin HB, Comert M. Neural cell adhesion molecule-180 expression as a prognostic criterion in colorectal carcinoma: Feasible or not World J Gastroenterol 2007; 13(41): 5476-5480

Exclusion of common bile duct stones prior to gallstone operations

Tue, 30 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) CBDS occur in 7-20% of all patients undergoing a gallstone operation and may complicate the course of surgery. Although intraoperative x-ray investigation was routinely performed to diagnose CBDS in the pre-laparoscopic era, its use during the laparoscopic era has been debated. Consequently, other techniques for diagnosing CBDS have been introduced. For example, preoperative liver function test (LFT; s-bilirubin and s-ALP) results, if abnormal, might be diagnostic for CBDS. However, some patients might have normal LFT despite coexisting CBDS. Ultrasonography is the major diagnostic modality used to diagnose gallstones, but is less helpful for diagnosing CBDS. Computed tomography is rarely useful for diagnosing gallstones. Magnetic-resonance-cholangio-pancreatography (MRCP) has high specificity and sensitivity, with accuracy similar to that of ERCP (Endoscopic-Retrograde-Cholangio-Pancreatography), but its accuracy depends on the size and anatomical location of a gallstone. In addition, MRCP is not widely available, and unlike ERCP, does not allow the endoscopic extraction of stones. ERCP is the most common technique used for both the diagnosis and treatment of CBDS. It is, however, expensive, invasive, technically demanding and associated with small but significant morbidity.

In this article, 200 consecutive patients with symptomatic gallstones disease operated on by laparoscopic cholecystectomy were retrospectively included and followed up 2-24 months after surgery. Three simple and routinely performed diagnostic variables, i.e., clinical history of patient (history of jaundice, pancreatitis or cholangitits), abnormal LFT results and/or dilated common bile duct (either alone or in combination), for diagnosing/excluding CBDS were evaluated. The results were statistically analyzed by calculating the sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of each with special attention given to NPV, which is the proportion of patients with negative test results who are correctly diagnosed. Higher NPV indicates higher sensitivity for excluding CBDS.

Twenty five patients were found to have CBDS (12.5%). As a single diagnostic test, ultrasonography showed higher sensitivity, specificity, and negative/positive predictive values than both medical history and LFT. As a triple diagnostic modality, the combination of medical history, ultrasonographic findings, and LFT results was shown to be the best diagnostic modality to exclude CBDS (NPV of 97. 3 %).

The authors concluded that using a combination of three routinely used diagnostic components as a triple diagnostic modality can increase the diagnostic accuracy of CBDS. This test is recommended for excluding CBDS and to identify patients in need of other investigations, such as MRCP or ERCP. The availability and non-invasiveness of this triple diagnostic test are additional benefits.

Attenuation of NASH by stimulation of free fatty acid metabolism

Fri, 26 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Medically-complicated obesity is a societal problem that needs to be solved. Liver disease, specifically non-alcoholic steatohepatitis or NASH, is just one of the many complications of increased body weight. Treatment options for NASH are limited, and therefore there is an unmet need for pharmacologic treatment of this liver disease. A recent article in World Journal of Gastroenterology by Dr. Baski-Bey et al. offers a helping hand to potentially aid in abolishing the occurrence of NASH in the population. The article describes how administration of a constitutive androstane receptor (CAR) agonist (TCPOBOP) can induce genes involved in fatty acid microsomal omega-oxidation and beta-oxidation pathways, resulting in a reduction in the occurrence of NASH in mice fed the methionine choline deficient (MCD) diet. The MCD diet, when fed to rodents, rapidly produces hepatic steatosis and steatohepatitis by blocking fatty acid oxidation.

Currently, the etiopathogenesis of NASH remains to be defined. In hepatic steatosis, an excess of non-esterified fatty acids are released from peripheral tissues into the serum. These excess serum-free fatty acids are discharged by the liver, where they are esterified and accumulate as neutral fat, secondary to a limited capacity to oxidize excess fatty acids. A potential strategy to protect the liver from hepatic steatosis would involve mechanisms to enhance hepatic fatty acid oxidation. Hepatic fatty acid oxidation occurs by three pathways: beta-oxidation is the predominant pathway; peroxisomal beta-oxidation occurs within peroxisomes and is rate-limited by the peroxisomal L-bifunctional enzyme (L-PBE), acetyl-COA oxidase (ACO) and urate oxidase (UO); the third pathway is omega-oxidation, which occurs in the endoplasmic reticulum. This pathway is dependent upon expression of the cytochrome enzymes CYPA410 and CYP4A14. Stimulation of these pathways either individually or collectively could help remove excess free fatty acids from the liver and diminish the occurrence of NASH.

Nuclear receptors are transcription factors that regulate metabolism of various biologic compounds. In particular, the constitutive androstane receptor (CAR), which is highly expressed in the liver, is a biosensor for endo- and xenobiotic compounds, such as toxic bile acids and steroids. CAR mediates the induction of detoxifying enzymes in humans by administration of the widely used anti-epileptic drug, Phenobarbital, and in mice, by the potent synthetic inducer, 1, 4-bis-(2-(3, 5,-dichloropyridyloxy)) benzene (TCPOBOP). CAR is viewed as a general hepato-protective response factor, as it detoxifies potentially injurious endo- and xenobiotics, and serves as a hepatic anti-apoptotic agent by increasing transcriptional expression of the anti-apoptotic protein, Mcl-1. In the article, Dr. Baskin-Bey demonstrated that CAR also protects the liver from injurious endobiotics, such as free fatty acids.

In summary, the principle findings of this study correspond to the effect of CAR's modulation of NASH in a murine model. The authors observed how TCPOBOP stimulation of CAR in the MCD-fed mouse can reduce hepatic steatosis. They witnessed a significant reduction in hepatic percentage fat and serum lipid levels after dispensation of TCPOBOP. They also noted a slash in hepatic inflammation and apoptosis in animals with simultaneous increased expression of genes involved in microsomal omega-oxidation and peroxisomal beta-oxidation pathways. Therefore, this research by Dr. Baskin-Bey et al. merits review by endocrinologists, hepatologists, bariatric surgeons, and any clinician with an eye on the obese patient.

The largest colonic lipoma to date

Fri, 26 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Colonic lipomas have been found in related literature. One extremely rare case was recently reported in the November 14 issue of the World Journal of Gastroenterology because of its maximum diameter of 8.5 cm. The article discussed age and sex factors, clinical and histopathological findings, diagnostic methods and treatment by reviewing the present case and previously available literature.

The article reported one patient who presented to Dr. Li-Sheng Jiang of West China Hospital of Sichuan University, China, in 2007. The patient experienced changes in bowel habits (7-10 times daily), passing fresh blood and mucus per rectum, abdominal distension, anorexia and weight loss. Dr. Li-Sheng Jiang suggested that colonoscopy or computed tomography (CT) should be performed again due to the previous unclear diagnosis, but this was refused by the patient. In view of his age, symptoms and related examinations, the possibility of colonic malignancy could not be precluded, and left hemicolectomy was subsequently planned.

At laparotomy, an 8.5 cm �� 7 cm �� 6.5 cm yellowish polypoid lesion with numerous areas of ulceration on its surface was seen arising from the descending colon. The lesion almost obstructed the whole lumen, and resulted in dilatation of the proximal colon. However, microscopical examination confirmed that such a large lesion was only located on the submucosa, without invasion of the serosa. In the end, local resection was performed instead of left hemicolectomy.

The clinicopathologic features of symptomatic lipomas are summarized in table by reviewing the present case and previously available literature. The following five points have been found by Dr. Li-Sheng Jiang: (1) the most common signs and symptoms include abdominal pain (42.4%), bleeding per rectum (54.5%) and a change in bowel habits (24.2%); (2) there is a female predominance (66.7%) ; (3) the most common age is the fifth or sixth decades of life; (4) the most typical site for solitary colonic lipoma is the ascending colon (45.5%); (5) the multiple lesions are summed in up to 6.1% of cases.

To increase the rate of preoperative diagnosis, Dr. Li-Sheng Jiang has analyzed the advantages and disadvantages of barium enema, computed tomography, magnetic resonance imaging and colonoscopy. Meanwhile, many therapeutic interventions have been introduced by reviewing the related literature.

On the basis of the present case and the published literature, Dr. Li-Sheng Jiang has proposed the indications of surgical removal and reminds us that colonic lipoma can also exist in patients with significant symptoms. This case is surely worth the attention of both doctors and the public at large.

LIALDA demonstrates prolonged release of mesalamine in an in vitro study using a simulated colon

Wed, 17 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Philadelphia, PA � October 17, 2007 � According to a study using a dynamic in vitro gastrointestinal tract system, Shire plc's (LSE: SHP, NASDAQ: SHPGY, TSX: SHQ) ulcerative colitis drug LIALDA� (mesalamine) demonstrated a delivery system where the majority of the drug�s active ingredient, 5-aminosalicyclic acid (5-ASA), is released over a prolonged period in the simulated colon. The colon is the site of inflammation in ulcerative colitis. In this in vitro model, after the LIALDA tablet passed through the simulated stomach, small intestine and colon compartments, the majority of 5-ASA within each tablet was released in the simulated colon (nearly 90 percent in simulated fasted state and 81 percent in the simulated fed state). Less than 1 percent of the 5-ASA was released from the tablet in the simulated stomach and small intestine. The study used the TNO Gastrointestinal Model, or TIM, which simulates a human stomach, small intestine and colon. The findings were published in the July/August issue of Advances in Therapy.

�To our knowledge, traditional, delayed-release 5-ASA formulations have no mechanism for prolonging the release of 5-ASA once the tablet enters the colon, which may lead to the majority of 5-ASA being released immediately upon entering the colon instead of in the areas most likely to be inflamed,� said lead study investigator and Senior Director of Pharmaceutical Sciences at Shire, Srini Tenjarla, PhD. �Using the TIM system, a well-known and widely used system that mimics the fate of ingested products in the human adult GI tract, we were able to demonstrate that LIALDA tablets provide maximum release of 5-ASA in a prolonged manner, with minimal formulation disintegration and release in the simulated small intestine.

The TIM system allowed us to observe that after exposure to the simulated stomach and small intestine and immediately prior to being introduced into the simulated colon compartment, the LIALDA tablets had a swollen appearance and the first appearance of cracks on the outer tablet coating. This demonstrates that very little drug is released in the simulated stomach and small intestine and suggests that the majority of mesalamine is released in the simulated colon,� said Dr. Tenjarla.

LIALDA with Multi Matrix System (MMX�) Technology combines a pH-dependent gastro-resistant coating, which delays the release of the medication to the colon, with a tablet core containing mesalamine with hydrophilic and lipophilic excipients. LIALDA is the only ulcerative colitis treatment that utilizes MMX Technology.

In two pivotal phase III clinical studies, LIALDA was shown to be superior to placebo in inducing remission and treating the symptoms of mild-to-moderate UC. LIALDA was generally well tolerated.

Patients may have sweet and effective way to prepare for upper GI endoscopy: an anesthetic lollipop

Tue, 16 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) OAK BROOK, Ill. � October 16, 2007 � Researchers at the American University of Beirut Medical Center (AUBMC) in Lebanon have found that administering a lidocaine lollipop as a single-agent anesthetic to patients undergoing an upper gastrointestinal (GI) endoscopy procedure eliminated the need for sedation in the majority of patients. The research appears in the October issue of Gastrointestinal Endoscopy, the monthly peer-reviewed scientific journal of the American Society for Gastrointestinal Endoscopy.

Upper endoscopy allows physicians to examine the lining of the upper part of the GI tract, which includes the esophagus, stomach and duodenum (first portion of the small intestine). It is often done under sedation to assure patient comfort. Upper endoscopy helps physicians evaluate symptoms of persistent upper abdominal pain, nausea, vomiting, or difficulty swallowing. It is the best test for finding the cause of bleeding from the upper GI tract and is also more accurate than X-rays for detecting inflammation, ulcers, and tumors of the esophagus, stomach, and duodenum.

�A significant portion of the complications, as well as the cost, of upper gastrointestinal endoscopy are often attributed to conscious intravenous sedation. In this study, we compared the efficacy of topical lidocaine administered in the form of a lollipop as a single-agent anesthetic with the conventional lidocaine spray, and determined whether it decreased the need for or the amount of intravenous sedation,� said study lead author Assaad Soweid, MD, FASGE, American University of Beirut Medical Center. �We found that 32 percent of the patients given the lidocaine lollipop required intravenous sedation compared with 96 percent of the patients who received the spray. The lollipop proved to be a safe and well-tolerated topical anesthetic. It is quite promising and may be particularly important for use with the elderly, patients who have comorbidities and in office-based endoscopy.�

Lollipops have been successfully used to provide anesthesia to children before painful procedures. The concept of using a lidocaine lollipop as a single-agent anesthetic in upper endoscopy is novel and has not been reported in medical literature. Medications to achieve sedation, however, may cause potential side effects such as respiratory depression, hypotension (low blood pressure) and paradoxical agitation, in which the patient becomes agitated rather than sleepy from the sedation. These side effects happen more so in elderly patients and those with comorbid illnesses.

The lollipop used in this study was developed by the anesthesia department in collaboration with the pharmacy department at AUBMC. Fifty grams of white sugar were heated until liquefied; an equal amount of golden maple syrup was slowly added. For each lollipop, 3 mL of this mixture were poured into a small cylindric container, to which 300 mg of lidocaine hydrochloride salt was added and stirred. As the the mixture cooled and solidified, a small plastic stick was plunged at one end for holding the lollipop. The ready-to-use lollipops were then labeled and stored in a refrigerator.

Is the spleen able to prohibit tumor cell proliferation?

Tue, 16 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Primary and metastatic tumors of the spleen are described as unusual, excluding involvement by lymphoma. Indeed, isolated splenic metastasis from colorectal carcinoma is not a common occurrence. Its rareness has been hypothetically explained by several characteristics of the spleen, such as anatomical, histological and immunological features.

One case of isolated splenic metastasis from colonic carcinoma with a concomitant splenic abscess conducted by the research group of Dr. Adolfo Pisanu from Universit�� degli Studi di Cagliari has been recently reported in the November 7 issue of the World Journal of Gastroenterology because of the interesting characteristics of this rare clinical entity.

Surprisingly, only 41 cases of isolated splenic metastasis from colonic carcinoma have been reported in the world literature. The rareness of splenic metastasis arising from colonic carcinoma suggests the existence of some mechanism that prohibits tumor cell proliferation in the spleen.

Anatomical and immunological characteristics may be reasons for the rarity of isolated splenic metastasis. Because the spleen is the second largest organ of the immunological system, immune surveillance appears to potently inhibit tumor cell proliferation. Moreover, experimental studies have shown that the growth rate of cancer cells injected into the spleen is significantly lower than that of the same cells injected into the liver.

The diagnosis of isolated splenic metastasis is generally made by imaging studies during the diagnostic evaluation of a colonic cancer. Only a few patients with splenic metastasis become symptomatic because of the presence of an associated splenic abscess or spontaneous rupture of the spleen.

When colorectal cancer is suspected, careful examination of the abdominal CT scan can allow early diagnosis of a splenic involvement by the tumor. Clinicians must pay close attention to the spleen for the early diagnosis of isolated splenic metastasis when routinely evaluating abdominal CT scan and abdominal ultrasonography following surgery for colorectal cancer.

Splenectomy followed by chemotherapy seems to be the preferred treatment of isolated splenic metastases from colorectal carcinoma. Literature review suggests there might be a significant improvement of long-term survival following splenectomy for metachronous splenic metastasis from colonic carcinoma. Nevertheless, prognosis for synchronous splenic metastasis seems to be related to the advanced stage of the disease.

Finally, the spleen is considered unfavorable to the development of metastases but the reason for this is not clearly understood. Following the small number of cases reported in the literature, no definitive conclusions can be drawn. Therefore, the researchers are looking forward to new studies to elucidate this issue.

First colonoscopy with removal of polyps linked to reduction in colon cancer death

Mon, 15 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Philadelphia, PA, October 15, 2007 � Using a model to predict reductions in death from colorectal cancer, epidemiologists and clinical researchers from Memorial Sloan-Kettering looked at the relative effect of an initial screening colonoscopy which clears pre-cancerous polyps from the colon versus surveillance follow-up colonoscopy. Ann G. Zauber, Ph.D., Sidney J. Winawer, M.D., MACG and colleagues presented their findings at the Annual Scientific Meeting of the American College of Gastroenterology.

�The model demonstrated a dramatic reduction in expected colorectal cancer mortality with initial polypectomy with or without surveillance, and suggests that the initial polypectomy accounts for the major component of the mortality reduction,� explained Dr. Zauber.

Using a �MISCAN� model, researchers used National Polyp Study data to predict colorectal cancer mortality among three groups of patients: those with no initial removal of polyps or follow-up surveillance by colonoscopy, compared to patients with only initial polypectomy, and those with both polypectomy and follow-up surveillance. The model predicted mortality of up to thirty years after the initial colorectal exam and removal of pre-cancerous polyps.

According to Dr. Zauber, the major effect on colorectal cancer mortality reduction produced by the initial polypectomy rather than the surveillance colonoscopies is consistent with the low incidence of advanced adenomas observed during National Polyp Study (NPS) follow-up (i.e., pre-cancerous growths in the colon larger than 1 cm, polyps with a villous component, high grade dysplasia or invasive colorectal cancer.)

Dr. Zauber and her colleagues suggest that these findings may support the recommendation to lengthen the interval to six or more years for follow-up surveillance for patients who have polyps removed. Current recommendations by the American College of Gastroenterology call for surveillance colonoscopy in three to five years for follow-up of patients with prior colorectal cancer, prior adenomas or disease with causes increased risk of colorectal cancer.

An editorial by colorectal cancer expert T.R. Levin, M.D, FACG in the August issue of the American Journal of Gastroenterology offers an overview of post-polypectomy surveillance. According to Dr. Levin: �Postpolypectomy and postcancer resection surveillance are among the most common indications for colonoscopy in clinical practice. Together, they account for more than one in five colonoscopies in the Clinical Outcomes Research Initiative (CORI) database. Survey results have also demonstrated that postpolypectomy surveillance for small adenomas and hyperplastic polyps is often recommended by specialists and primary care physicians more frequently than guideline recommendations.�* Dr. Levin commented on a study in the same issue of the American Journal of Gastroenterology by Brenner et al. from Germany which Levin believes presents additional evidence to justify extending colonoscopy intervals following polypectomy to five years. According to Levin, performing excessive surveillance colonoscopy is a problem for two reasons. It drains resources better used for initial colorectal cancer screening and diagnosis, and patients are exposed to potential risks associated with each colonoscopy with little benefit.

According to ACG President Dr. David A. Johnson, �there is growing evidence to support the extension of surveillance to longer intervals, all subject to optimal clearing of the colon of precancerous polyps � which is contingent on adequate resection at the time of polypectomy and adequate visualization of the colon, which depends on adequate bowel preparation, as well as efforts by the endoscopist during the exam. Although given the constraints of a modeling study such as this one from Sloan-Kettering, there need to be prospective trials to support and validate longer colorectal cancer surveillance intervals before changing the current recommendations.�

New studies reveal that night-time acid reflux can impact sleep

Mon, 15 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Philadelphia, PA, October 15, 2007� According to results of a survey presented at the 72nd Annual Scientific Meeting of the American College of Gastroenterology, nighttime acid reflux, along with some of the less typical manifestations or symptoms of gastroesophageal reflux disease (GERD), is associated with significant sleep impairment.

In a recent national survey, researchers assessed the prevalence of sleep impairment among people with GERD and people without GERD based on response to an Internet survey of a general population of U.S. adults. Using a validated GERD screening tool, 701 respondents were identified with GERD and the remaining were controls. Bonnie Dean, MPH, PhD, of Cerner LifeSciences, Ronnie Fass, MD of the University of Arizona and their research team found that sleep impairment was more common among people with GERD (41.9 percent) than those without GERD (19.4 percent). Researchers found that 49.5 percent of respondents with nighttime GERD reported sleeping poorly often or most of the time, compared to 36.7 percent of people with daytime GERD.

Using the survey, researchers also assessed sleep impairment among patients experiencing frequent nighttime atypical manifestations of GERD. In this case, Dr. Dean and her colleagues evaluated the subgroup of respondents with GERD, as identified using the validated GERD screener. They found that atypical manifestations or symptoms of GERD (i.e. coughing, sore throat, snoring, wheezing, choking, and chest pain) were common among those with acid reflux. Of GERD patients, 74 percent had at least one nighttime atypical manifestation. For almost every daytime and nighttime atypical manifestation assessed, more than 20 percent of GERD patients reported their occurrence as frequent (more than 2 days or nights per week). Researchers also found that sleep impairment was more common among GERD patients with atypical manifestations compared to GERD patients with only typical or classic symptoms such as heartburn and acid regurgitation. For eight of the nine nighttime atypical manifestations assessed, the proportion of GERD cases reporting sleep impairment was significantly higher for GERD cases with the atypical manifestation compared with GERD cases without the atypical manifestation.

�Awareness of nighttime reflux, atypical manifestations, and associated sleep complaints should allow more complete evaluation and treatment of GERD patients,� said Dr. Dean about this project.

Tips for Calming Nighttime Acid RefluxHeartburn and other gastroesophageal reflux disease (GERD) symptoms experienced during the night commonly cause sleep disturbances, including arousal from sleep, increased wakefulness and overall poor sleep quality.

Here are several tips to help reduce nighttime acid reflux so you can sleep better:

Researchers warn that gastric bypass surgery may cause post-op nutrient deficiencies

Mon, 15 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Philadelphia, PA, October 15, 2007� Two studies by a group of researchers at Washington Hospital Center highlight potential postoperative nutritional deficiencies among patients who undergo gastric bypass surgery to treat obesity. Research presented at the 72nd Annual Scientific Meeting of the American College of Gastroenterology by Dr. Frederick Finelli and Dr. Timothy Koch suggests that a potentially serious condition can emerge after gastric bypass surgery known as small intestinal bacterial overgrowth that has an impact on absorption of vitamins, minerals and micronutrients such as calcium and zinc.

According to the Washington Hospital Center team, this is a serious issue with widespread implications as approximately 150,000 patients this year will have gastric bypass surgery, and there exists wide variation in surgical techniques. According to Dr. Koch, �patients may develop bacterial overgrowth that interferes with their ability to absorb nutrients, even if they are taking supplements as directed after surgery. Only a gastroenterologist can evaluate these potentially serious small intestinal disorders.�

Dr. Koch and his colleagues hypothesized that by altering the gut ecology, gastric bypass surgery could induce calcium deficiency. Surgical changes to the stomach to create the �gastric pouch� in the Roux-en-Y procedure impact the number of acid producing cells in the stomach lining. Furthermore, many gastric bypass patients are given acid suppressing drugs after their surgery. Researchers suspect that the reduction in acid, known as achlorhydria, contributes to the overgrowth of bacteria in the small intestine. According to Dr. Koch, competition between bacteria and the human host for ingested nutrients leads to malabsorption and potentially serious complications due to micronutrient deficiency.

In the studies presented at the ACG, Dr. Koch�s team found that in a retrospective review of gastric bypass patients, almost all of the 43 patients who had hydrogen breath testing for small intestinal bacterial overgrowth (�SIBO�) had abnormal findings. Researchers also measured levels of calcium and found that those with SIBO had lower calcium levels. Researchers warn that calcium malabsorption may increase the risk for developing osteopenia (low bone mineral density), osteoporosis (a progressive bone loss that may increase the risk of fractures), or osteomalacia (softening of the bones due to defective bone mineralization.)

In a second study, Dr. Koch and his colleagues reviewed that same group of patients to examine the relationship between SIBO and zinc deficiencies, and found a positive correlation. In the case of zinc absorption, the physiological evidence supports zinc absorption in the jejunum by a trancellular route involving a zinc-specific transporter, Zip4.

In the Roux-en-Y procedure, surgeons make the stomach smaller by creating a small pouch at the top of the stomach using surgical staples or a plastic band. The smaller stomach is connected directly to the middle portion of the small intestine (jejunum), bypassing the rest of the stomach and the upper portion of the small intestine (duodenum). Dr. Koch explained that the wide variation in surgical techniques for gastric bypass means that patients should be aware of the risk of problems absorbing nutrients, and should consult with a gastrointestinal specialist.

2 studies highlight the risks and significant health-care costs of NSAIDs injury

Mon, 15 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Philadelphia, PA, October 15, 2007 � Patients underreported their use of common but potentially dangerous over-the-counter pain medications known as NSAIDs, according to research presented at the Annual Scientific Meeting of the American College of Gastroenterology. �This is a serious issue given what we know about the significant risk of injury and bleeding in the GI tract in patients using NSAIDs,� said David Johnson, M.D., FACG, one of the researchers and President of the America College of Gastroenterology.

Serious gastrointestinal complications such as bleeding, ulceration and perforation can occur with or without warning symptoms in people who take NSAIDS (non-steroidal anti-inflammatory drugs.) Ulcers and gastrointestinal bleeding are serious health problems in the United States. With millions taking NSAID pain medications every day, it is estimated that more than 100,000 Americans are hospitalized each year and between 15,000 and 20,000 Americans die each year from ulcers and gastrointestinal bleeding linked to NSAID use.

Of particular concern are patients with arthritic conditions. More than 14 million such patients consume NSAIDs regularly. Up to 60 percent will have gastrointestinal side effects related to these drugs and more than 10 percent will cease recommended medications because of troublesome gastrointestinal symptoms.

Dr. Johnson and his colleagues at Eastern Virginia Medical School administered a survey to patients in a private GI practice after a written and verbally confirmed report of current medications to nursing staff. Almost one in five respondents to the survey noted use of an NSAID that had not been reported verbally to nursing staff, including 8 percent who reported daily use. For 22 percent of respondents, they did not think the medications were important enough to list, while 30 percent cited the fact that the drugs were not prescribed by a physician. �This reflects a common misperception that these medications are insignificant or benign when actually their chronic use, particularly among the elderly and those with conditions such as arthritis, is linked to serious and potentially fatal GI injury and bleeding,� noted Dr. Johnson.

Physician experts from the American College of Gastroenterology warn that patients who take over-the-counter pain medications on a regular basis should talk with their physician about the potential for ulcers and other GI side effects.

Recent research suggests a role for acid suppression therapy with a proton pump inhibitor (PPI) for patients at risk of developing stomach ulcers due to long-term use of NSAIDs. In another study presented at the American College of Gastroenterology, a VA researcher, Neena S. Abraham, M.D. looked at the burden of cost from hospitalization for GI bleeding related to NSAID use, and conducted a cost benefit analysis of using PPIs to help protect against serious potential injury to the GI tract.

�Our analysis of a large patient population suggests that it is cost beneficial to administer a proton pump inhibitor with NSAIDs and points to significant savings in hospital costs relating to GI injury and bleeding in the Veterans� Administration medical setting,� explained Dr. Abraham.

Dr. Abraham and her colleagues reviewed prescription records linked to inpatient, outpatient and death files for the VA medical system and Medicare. In an overall population of almost half a million veterans, Dr. Abraham identified 3,200 events of GI bleeding, of which 36 percent were treated by the VA. A review of their prescription and hospitalization records revealed that half of those with GI bleeding events were hospitalized. Importantly, the one third of patients with GI bleeding events prescribed a PPI were 60 percent less likely to be hospitalized. Their overall median total medical costs were significantly lower than patients who were not prescribed a PPI.

�This reduction in the risk of hospitalization is where significant savings occur due to lower utilization of health resources, endoscopy and surgery, not to mention the impact on patients� quality of life,� explained Dr. Abraham. While there are costs to treat patients on NSAIDs prophylactically with PPIs, these findings suggest that reduced hospitalization costs offset higher pharmacy costs.

�These are powerful data, especially because of the high risk for GI bleeding in elderly patients who are in the highest risk category for GI bleeding,� according to Dr. Abraham.

Portal vein thrombosis is common in extraportal vein obstruction

Fri, 12 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Among the 118 patients with portal vein thrombosis, noncirrhotic and nontumoral extrahepatic portal vein obstruction are young and present with well tolerated bleed. Cirrhosis and tumor related portal vein thrombosis patients are older and have grim prognoses. Hypercoagulable state as a cause of portal vein thrombosis is less common. The idiopathic group comprises the second largest number of patients.

A research article to be published on October 21 in the World Journal of Gastroenterology addresses the etiology and clinical outcome of portal vein thrombosis. The research team led by Dr. Pankaj Jain and Dr. Sandeep Nijhawan from Sawai Man Singh Hospital, Jaipur worked on patients with portal vein thrombosis for two years. The researchers had observed that patients with portal vein thrombosis in the two groups behaved differently in etiology, presentation and prognosis. Therefore, they collected data from their centre to verify the differences.

The researchers included cirrhosis and tumor-related AND non-cirrhotic non-tumoral extrahepatic portal venous obstruction. The large sample size allowed them to obtain significant results and draw very reliable conclusions.

Factor V Leiden mutation was present in 2% of cases and is uncommon in India. Umbilical sepsis in childhood or catheterization of umbilical veins in the neonatal period may be responsible for extrahepatic portal vein obstruction in the developing countries.

Extrahepatic portal vein obstruction (EHPVO) patients were young and commonly presented with features of hematemesis, hypersplenism, pain abdomen and abdominal distension. Ten patients had acute PVT and two had presentation as acute Budd-Chiari syndrome. Cirrhosis and tumor-related portal vein thrombosis presented with abdominal distension, abdominal pain and jaundice. On follow-up of a mean period of 7 months (range 1-24 months), 48% patients had died. The role of JAK2mutation in the early diagnosis of overt or silent myeloproliferative disease cannot be undermined but requires standardization.

Therefore, portal vein thrombosis is common in cirrhotic, tumor and non-tumoral, non-cirrhotic extraportal vein obstruction. EHPVO is a benign disease whereas cirrhotic and tumoral-related portal vein obstruction has a grim prognosis. Any patient with portal vein obstruction, in whom secondary cause is not known, should have hypercoagulable work up done to find out a treatable cause. Furthermore, as a primary prevention antenatal care has to be more meticulously planned and carried out.

Dr. Pankaj Jain (doing a fellowship in gastroenterology) and Dr. Sandeep Nijhawan (Professor of Gastroenterology) are working in the Department of Gastroenterology at Sawai Man Singh College and Hospital, Jaipur.

The experts opined that this research presents a large series of patients with portal vein thrombosis which they believed will be useful to the practitioners.

18F-DG PET/CT can highly increase the detection of colorectal cancer

Wed, 10 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Combined positron emission tomography and computed tomography (PET/CT) is currently widely used in the clinical diagnosis of cancer to provide functional and morphological imaging. The value of PET/CT in detection of the recurrence and metastasis of colorectal cancer (CRC) was recently confirmed in an article appearing in the October 7 issue of the World Journal of Gastroenterology.

The research performed at the Department of Medical Oncology, Jinling Hospital, China. Dr. Chen and his colleagues observed a total of 68 postoperative CRC patients, 48 male and 20 female, who were examined in the Jinling Hospital PET/CT Center between August 2004 and August 2006. After PET/CT imaging, recurrence and/or metastasis were confirmed in 82.4% (56/68) of the patients, with 91.7% (22/24) cases with elevated serum CEA levels. PET/CT detected more lesions than CT or ultrasonography alone in 30.4 % (17/56) of the cases of recurrence and/or metastasis.

CRC is the most common gastrointestinal malignancy, and its incidence and mortality are rising in China. Radical resection remains as the major means of CRC management, but recurrence and/or metastasis occurs in 30 to 50 percent of patients after surgery. An accurate diagnosis of postoperative local recurrence and distant metastasis is crucial for prescribing optimal individualized management and thus elevating the survival rate. However, CRC is not normally detected by traditional imaging techniques, such as CT, magnetic resonance imaging (MRI) and ultrasonography, until the lesion reaches a considerable size.

PET/CT imaging provides a whole-body overview in one examination, and can detect abnormal glucose metabolism before the morphological changes of a lesion can be identified. In the current study, the treatment plans of 16.2% (11/68) of the cases were altered based on the PET/CT findings. Local metastasis focus was detected in the liver or lung in three cases; accordingly surgical resections were conducted instead of intravenous chemotherapy. Conversely, disseminated metastases were detected in six cases, and thus intravenous or oral chemotherapy was prescribed instead of surgery.

To most CRC patients, the cost of PET/CT is more expensive than traditional imaging techniques. However, Dr. Chen believes an optimal, individualized treatment plan is the most important aspect of treating this malignancy, as such a plan can indeed prolong the life and lessen both the mental and economical burdens of patients.

The researchers demonstrated the superiority of 18F-DG PET/CT in the imaging diagnosis of the postoperative recurrence and/or metastasis of CRC by conducting a retrospective study of 68 patients. Their findings are valuable when considering the choice of imaging techniques for detecting the recurrence and/or metastasis of CRC.

Can liver cirrhosis be partially cured?

Wed, 10 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) The diffusion of hepatitis C virus infection worldwide is astonishing. Liver cirrhosis is present in at least 10-20% of these infected patients, with highly increasing health care and emotional costs. In patients with compensated (early stage) hepatitis C virus-related cirrhosis, antiviral combined therapy offers an interesting rate of response, ending in viral clearance. Unfortunately post-therapy data on different aspects of the illness, such as the residual liver function, measured as Total Overnight Salivary Caffeine Assessment (TOSCA, a liver test of microsomal function), and hepatic hemodynamics to indirectly evaluate the portal hypertension, measured as the Resistive Index of Splenic Artery (SARI) at Ultra Sound Doppler are still lacking, because to date only the survival rate and hepato-carcinoma appearance have been studied in depth.

Thirty five cirrhotic patients (24 grade A5 and 11 grade A6 of the Child-Pugh classification system, used to assess illness severity), with active virus replication and treated for a mean period of three years with moderate doses of Interferon-alpha and Ribavirin were compared to a cohort of 36 patients with similar characteristics and without antiviral treatment. TOSCA was determined at the starting point and three times throughout the course of therapy after a mean period of one year. Meanwhile, the SARI was only measured at the beginning and end of the study.

The more notable findings are as follows. Thirteen treated patients showed a significant TOSCA improvement. A reduction greater than 20% on the Resistive Index of Splenic Artery was obtained in eight of the patients with improved liver function. This previously abnormal Doppler parameter showed a clear total decreasing tendency at the end of therapy. Hepatitis C virus clearance was achieved in four patients at a median period of eight months of combined therapy. In the cohort of non-treated cirrhotic patients, not only the considered parameters remained unchanged, but three patients ended with a worse Child-Pugh score.

Dr. Tarantino and his team from the Federico II University Medical School believes that moderate-dosed, prolonged antiviral therapy can make stable or ameliorate residual liver function, the entity of portal hypertension and the compensation status, all at acceptable costs. In this way, more severe liver cirrhosis complications, such as variceal hemorrhage, the appearance of refractory ascites and advanced encephalopathy, are can be delayed, thereby prolonging the survival period of many patients. His team, however, still emphasises the need to evaluate individuals affected by liver cirrhosis using alternative, non-invasive, and easily repeatable parameters of outcome to better understand the progression of this illness.

Interleukin-8, key marker for colorectal cancer treatment

Tue, 09 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Colorectal cancer (CRC) is currently one of the three most frequent malignancies in Western industrial nations. Although the 5-year survival rate for patients with early stage and local CRC approaches nearly 90%, survival is dramatically decreased by local recurrence and the development of distant metastases that primarily affect the liver, which are the predominant cause of CRC-related mortality.

Although IL-8 expression has been recently correlated with the tumorpathology of various carcinoma types, the role of IL-8 in tumor development and metastasis is still not fully understood and often discussed controversially. Moreover, it remains unclear whether IL-8 expression is related to cancer progression and metastatic potential in colorectal carcinoma tissues.

This issue was addressed by Dr. Rubie and colleagues from the University of the Saarland, Germany. The investigators report on a potential role of IL-8 in the development and metastatic spread of colorectal cancer in the October 7 issue of the World Journal of Gastroenterology.

The article investigates the expression profile of IL-8 in inflammatory (ulcerative colitis), non-malignant (colorectal adenoma) and CRC tissues of different tumor stages as well as in colorectal liver metastases (CRLM) along with their related primary colorectal tumors.

The major findings demonstrate significant IL-8 up-regulation in all inflammatory, non-malignant and malignant colorectal entities compared to their corresponding normal tissues. However, the magnitude of IL-8 expression in surgical CRC tissue specimens correlates with increasing tumor stages and, thus, also with the malignant status of colorectal cancer cells. Moreover, the investigators show for the first time that, irrespective of the tumor stage, IL-8 is significantly higher expressed in CRC tissues compared to inflammatory colorectal conditions and adenomas of the colon/rectum. Since such conditions often constitute prevalent pre-existing disease states in the pathogenesis of colorectal cancer, these results strongly suggest an association between IL-8 up-regulation and the development of CRC. In addition, significant IL-8 overexpression was found in CRLM in comparison to related primary colorectal tumors. Thus, this study not only suggests a correlation between IL-8 expression and the induction and progression of colorectal carcinoma, but also clearly points to a correlation between IL-8 expression and the development of CRLM.

Monitoring the IL-8 expression level in CRC patients may potentially help to assess the course of cancerous conditions and the prognosis of patients with respect to the development of CRLM. In this respect it is conceivable to monitor the IL-8 expression level in CRC patients that show no diagnosable symptoms of CRLM at the time of presentation, but may still carry a high risk for developing such metastases. A significantly up-regulated level of IL-8 might thus be a useful tool to evaluate the prognosis of patients with CRC with meaningful consequences of treatment. Thus, patients with a higher risk of developing CRLM may receive different treatment compared to patients with a lower risk of developing CRLM.

This study shows that IL-8 may serve as a useful indicator of poor prognosis and a putative target for the development of drugs in CRC therapy.

Stomach stem cell discovery could bring cancer insights

Wed, 03 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) ANN ARBOR, Mich. � Scientists have identified and described stem cells specific to several tissues and organs of the body � key master cells that give rise to the specialized cell types characteristic of that organ. But to date, it hasn�t been possible to pinpoint functioning stem cells in the stomach, either in laboratory animals or people.

Now, a group of University of Michigan Medical School researchers has succeeded in finding and manipulating a population of cells that strongly resemble stem cells in the stomachs of mice. They have been able to show that these cells, which they call �gastric progenitor cells,� can give rise to all the different types (or lineages) of specialized cells needed to form the functional stomach glands that line the lower portion of the stomach. This property of �multi-lineage potential� is considered a key stem cell property.

�The identification of these progenitor cells will not only aid in our understanding of normal cell turnover in the stomach, but could potentially open some new and exciting doors in our investigation of the origins of gastric cancer,� says Deborah Gumucio, Ph.D., a U-M developmental biologist and senior author of a study which appears online ahead of print in the journal Gastroenterology.

The epithelial cells that make up the millions of glands of the stomach are constantly turning over. Most of the mature functioning cells live only 20 to 60 days before being replaced by progeny of dividing resident stem cells. These stem cells are not only a constant source of new cells, but they represent an important reservoir for repair of damage to the stomach caused by injury or inflammation. In addition, since the stem cells are the longest-lived of the gastric cells, it is thought that these are the only cells that live long enough to accumulate the multiple mutations that can cause cancers. For these reasons, the ability to identify and manipulate stomach progenitor cells has been an important goal for decades.

�Before this work, we knew that stem cells existed in the stomach, but we had no way to precisely identify them,� says Gumucio, who directs the U-M Center for Organogenesis and is a professor in the Department of Cell and Developmental Biology at the U-M Medical School.

�There were no effective markers or tags that we could use to clearly discriminate the stem or progenitor cells from other cells. Now, for the first time, we have the experimental tools to ask important questions, like, �Does stomach cancer really arise from mutations in this progenitor cell population��

Stomach cancer is a major cancer killer outside the United States. It is the most common

cause of cancer deaths in much of East Asia and Latin America. In the United States, it is estimated that 21,260 people will be diagnosed with stomach cancer and 11,210 will die of it in 2007.

There are several types of stomach cancer, but one very prevalent type, called intestinal-type gastric adenocarcinoma, progresses through a defined series of steps. Initially, the insult is an inflammatory one, usually through infection by an acid-tolerant bacterium called Helicobacter pylori. The chronic inflammation eventually leads to changes in the character of the surrounding stomach cells and ultimately, over several years, to tumors. These tumors often arise in one particular area of the stomach. Interestingly, the progenitor cells that the Gumucio lab has identified are concentrated precisely in this tumor-prone area.

To spot and watch the progenitor cells at work, Gumucio�s team, under lead author Xiaotan T Qiao, Ph.D., a U-M Medical School research associate, had to get past the hurdle that has deterred the search for stomach stem cells so far � finding effective markers, which act like identification tags to make tracing possible. Qiao was able to identify the gastric progenitor cells and later explore their behavior because the cells could be effectively marked using a mouse model developed earlier in Gumucio�s lab.

�Since gastric cancers often occur in the context of inflammation, we were interested to determine whether these progenitor cells are affected by inflammatory conditions,� says Qiao.

�We were amazed to see that though these cells are normally very quiescent, that is, they don�t divide, inflammatory signaling proteins such as interferon gamma provide a potent stimulus for multiplication of these cells.�

Just what specific role these progenitor cells may play in inflammation and cancer is not clear yet.

�Are these cells good guys, bad guys or innocent bystanders We just don�t know,� Gumucio says. They could be cells that are in some ways predisposed to being cancer cells. Alternatively, they could be important reservoirs for repair of damage caused by injury or inflammation. In that case, having more of them could be a good thing, she says.

�These are probably not the only stem-like cells in the stomach,� adds Qiao. �This must be a subset of such cells, but they certainly represent an interesting subset, given their location in the stomach and their response to inflammation.� The Gumucio lab is working with additional new markers to find other stem-like cells in the stomach.

The researchers suspect the effort to understand stomach stem cells and their possible relationship to cancer will take many more twists and turns. Any therapies or prevention methods resulting from this early research are years away. An important next immediate step is to look in human stomachs to see if this type of stem or progenitor cell can be identified.

Married esophageal cancer patients fare worse in some quality of life aspects than single patients

Wed, 26 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Barcelona, Spain: In a surprising finding, American scientists have found that when battling oesophageal cancer, married patients don�t fare as well as their single counterparts in certain aspects of their quality of life.

In the study, presented today (Wednesday) at the European Cancer Conference (ECCO 14) in Barcelona, 212 oesophageal cancer patients and 489 patients with Barrett�s oesophagus, a non-cancerous condition linked to acid reflux, filled out two quality of life questionnaires a year apart. Changes in the scores between the two assessments were analysed according to marital status.

No differences in quality of life changes over time were seen between marital states in the patients with Barrett�s oesophagus. That finding was expected because the condition is not a potentially fatal one requiring stressful major treatment.

�In general, there were not major differences in quality of life between single and married oesophageal cancer patients, but there were slight differences in some aspects,� said the study�s lead researcher, Dr. Robert Miller, an assistant professor of oncology at the Mayo Clinic in Rochester, Minnesota.

For the single patients, quality of life scores relating to pain frequency, overall physical wellbeing and legal worries improved between the first and second questionnaire. However, married patients reported less improvement in their legal worries than the single patients did, and worsening physical wellbeing and increasing pain frequency over time.

�In the second questionnaire, single people rated their overall physical quality of life at a score 0.7 points higher on a scale of one to 10 than they did on the first questionnaire. However, for married people, the score dropped 0.4 points,� Miller said.

The results for pain frequency were similar, with the singles improving by 0.6 points and the married patients reporting a 0.9-point deterioration.

When it came to perceptions of legal worries, all patients reported improvement, but the singles moved 1.1 points up the scale, while the married patients gained only 0.2 points.

�These findings were surprising, as we thought we�d be demonstrating improved outcomes in married patients,� Miller said.

Most previous studies comparing the quality of life of married and single cancer patients, chiefly in breast but also in brain cancer, indicate that married people do better than single people, noted Miller. He said one reason why the current study came out differently could be that oesophageal cancer has a worse prognosis in comparison to some of the other types of cancers previously studied.

Also, there were approximately nine men to every woman in the oesophageal cancer group. This gender ratio may account for the difference between the latest results and those seen in studies of breast cancer patients.

�It�s hard to interpret why married patients didn�t do as well as single patients, but one explanation could be that having a family to support and care for when you have a serious and potentially life-threatening disease may increase a person�s worries, leading to a decrease in quality of life,� said Miller. �Being single may be associated with less negative changes in quality of life over time because the disease is more disruptive if you have others relying on one�s participation in family social and economic activities.�

Married patients diagnosed with oesophageal cancer may require extra diligence when evaluating pain and other somatic complaints, and there may be issues outside the standard concerns of medicine, Miller said.

Study makes progress in zoning in on biomarkers for better colon cancer treatment

Wed, 26 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Barcelona, Spain: New research has yielded a clearer picture of which biomarkers could help doctors more precisely target the treatment of colon cancer, bringing closer the day when patients who will not benefit from chemotherapy are spared it, while those that will, get the more aggressive treatment they need.

As with many other solid tumours, doctors plan treatment of colon cancer chiefly by staging the tumour, which involves assessing how deep it has infiltrated into the bowel wall and how far the cancer has spread. Generally, if the cancer has spread to the lymph nodes, chemotherapy is given after surgery to prevent recurrence.

�That approach is not very precise,� said the study�s lead investigator, Dr Arnaud Roth, a medical oncologist and chief of Oncosurgery at the University Hospital of Geneva, Switzerland. �Even if the lymph nodes are involved, at least half of those patients won�t ever suffer a relapse and could be spared chemotherapy. However, since there is no good tool to distinguish them from the people who have a high likelihood of relapse, all patients with cancer detected in lymph nodes are treated with chemotherapy.

�New tools are needed to make this distinction and biomarkers are one possibility,� said Roth, who presented a large study on this subject today (Wednesday) at the European Cancer Conference (ECCO 14) in Barcelona.

Since the decoding of the human genome, scientists have increasingly been looking for genes or protein biomarkers consistently over-expressed or under-expressed in cancer tissue to see if those markers can help better determine prognosis and tailor treatment for individual patients.

The study, by a team of European scientists which Roth coordinates, examines in one of the largest patient groups to date a broad panel of candidate biomarkers suspected of playing a role in colon cancer.

�The results are preliminary but extremely encouraging. This study will, we hope, clarify which biomarkers will be clinically useful, which are probably not and which will have the most impact. There have been a lot of studies of limited scope previously, but nothing conclusive,� Roth said.

The researchers examined potentially promising biomarkers in 1,564 samples, preserved as part of a chemotherapy study, of healthy and cancerous colon tissue from patients operated on in more than 368 hospitals in Europe. More than 10 molecular markers were investigated with a high success rate (>90%), demonstrating the method�s feasibility with routinely processed tissue.

�If one of those markers is strongly linked to the reaction to chemotherapy, it might be useful to test in a clinical trial its value in deciding whether to give chemotherapy or not,� Roth said.

�For instance, it�s early in our analysis, but SMAD4 is looking quite good, in that patients with high SMAD4 expression had a significantly better prognosis than those with low expression. It would have to be investigated further, but maybe patients who strongly express the SMAD4 gene don�t need any additional therapy after surgery.

�On the other hand, in this patient population with adjuvant therapy, we found that KRAS, a type of gene called an oncogene that is involved in regulating cell division, has no prognostic value whatsoever � zero. So we think KRAS can be abandoned as a potential prognostic biomarker for colon cancer,� Roth added.

Capsule endoscopy diagnoses more Crohn's disease recurrence after surgery than colonoscopy

Wed, 26 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) OAK BROOK, Ill. - September 26, 2007 � Research from La Fe University Hospital in Valencia, Spain shows that capsule endoscopy diagnoses more Crohn�s disease recurrence after surgery than colonoscopy. Capsule endoscopy led to changes in therapy for more than half of the patients studied. The research appears in the September issue of Gastrointestinal Endoscopy, the monthly peer-reviewed scientific journal of the American Society for Gastrointestinal Endoscopy.

Crohn�s disease is a chronic condition that causes inflammation in the gastrointestinal tract, most commonly affecting the small intestine and colon (large intestine). According to the Crohn�s and Colitis Foundation of America, approximately half a million people in the United States have Crohn�s disease. Researchers do not know what causes the disease and there is no cure, so the goal of treatment is to reduce the inflammatory response. Surgery becomes necessary when medication can no longer control symptoms. In most cases, the diseased segment of the intestines is removed, this is called a resection. The two sections of the remaining healthy intestines are joined together in a procedure called anastomosis. While patients may live symptom-free for years, surgery is not a cure and disease frequently recurs at or near the site of the anastomosis.

Colonoscopy is the gold standard in screening for colorectal cancer, which develops in the large intestine. It is effective in diagnosing diseases of the large intestine and in viewing the end part of the small intestine. Capsule endoscopy allows physicians to view the entire small intestine, but is not currently a method used to view the large intestine.

�Crohn�s disease occurs in both the small and large intestines. In this study we found that compared to colonoscopy, capsule endoscopy was able to identify Crohn�s disease recurrence in 62 percent of patients, whereas colonoscopy only identified inflammatory lesions in 25 percent of patients,� said the study�s lead author Vicente Pons Beltr�n, MD, PhD, La Fe University Hospital. �We believe this is due to capsule endoscopy�s ability to visualize the entire small intestine, including parts of the upper small intestine that colonoscopy is not designed to reach.�

Capsule endoscopy allows physicians to examine the lining of the middle part of the gastrointestinal tract, which includes the three portions of the small intestine (duodenum, jejunum, ileum). A tiny camera is contained inside of a pill that the patient swallows. It captures images of the gastrointestinal tract as it travels through the body and transmits the images to a computer so the physician can view them and make a diagnosis.

Patients and MethodsRecurrence after surgery to treat Crohn�s disease is frequent and unpredictable. The efficacy of post-surgery capsule endoscopy in detecting recurrence in patients with Crohn's disease is yet to be confirmed. The objective of this study was to assess the safety, accuracy, and therapeutic impact of capsule endoscopy. Twenty-four Crohn�s disease patients from La Fe University Hospital in Valencia, Spain who had ileocolonic resection, followed by reconnection of the ileum to the colon, were subjects in the study.

All patients were asymptomatic and not on any medical therapy for Crohn�s disease. Colonoscopy and capsule endoscopy were used to visualize and assess Crohn's disease at the anastomosis and in the remaining small intestine. Capsule endoscopy was performed within two weeks of colonoscopy. Investigators were blinded to the results of each technique. Patient comfort during the procedures was also recorded.

Results A colonoscopy was performed in all patients, although the end part of the small intestine could not be reached in three of them. Two of the patients had a narrowing in the small intestine, which precluded capsule endoscopy from being performed.

Recurrent Crohn�s disease was visualized in the remaining end of the small intestine with colonoscopy in six patients; capsule endoscopy identified five of these six patients plus another ten patients with disease recurrence higher up in the small intestine. A decision to modify therapy was made in 13 patients. Colonoscopy alone would have led to this decision in six patients; capsule endoscopy alone provided data in the remaining seven patients.

All patients preferred capsule endoscopy, an expected finding in this study where only one third of the patients undergoing colonoscopy received sedation. Researchers concluded that capsule endoscopy is of great use in the evaluation and treatment of recurrent Crohn�s disease. While colonoscopy remains the gold standard for evaluation of the colon and tissue acquisition, the capsule provides an invaluable window into the sizable small bowel inaccessible by colonoscopy. The two methods are complimentary in diagnosing and treating diseases of the gastrointestinal tract.

Molecular profiling can accurately predict survival in colon cancer patients

Tue, 25 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Barcelona, Spain: Researchers in The Netherlands have developed a method of accurately predicting which patients with colon cancer are most likely to have their disease recur after surgery and who would, therefore, be likely to benefit from additional chemotherapy.

Led by Professor Rob Tollenaar at Leiden University Medical Center and Dr Laura Van �t Veer at The Netherlands Cancer Institute, they have analysed for the first time the different expressions of genes in the entire genome of tumour tissues from 121 patients with stage II colon cancer who had not received adjuvant chemotherapy.

Prof Tollenaar, who is head of sections endocrine, gastrointestinal and oncologic surgery in the department of surgery, told a news briefing at the European Cancer Conference (ECCO 14) in Barcelona, today (Tuesday) that the full-genome molecular expression profiling had identified two groups of patients that had distinct clinical outcomes.

�Patients with stage II colon cancer have an overall five-year survival of about 80%,� he explained. �So far, no randomised clinical trials has shown significant benefit from giving adjuvant chemotherapy. Three-quarters of patients are cured by surgery alone and, therefore, less than 25% of patients would benefit from additional chemotherapy.

�Our analysis showed a cluster of 75% of the patients, of whom approximately 90% were likely to survive for at least five years with no distant metastases. In the second cluster of the remaining 25% of the patients, only about 65% of them had five-year survival without distant metastases, and this is the group who would be likely to benefit from adjuvant chemotherapy.

�This is the first time that the identification of a poor survival group has been based on genome-wide expression analysis and, therefore, it relates tumour biology more accurately to the outcome of disease.�

Further analysis of the results showed that patients in the �poor outcome� group were over three times (3.2) more likely to develop metastases than the patients in the �good outcome� group. This method of identifying �poor outcome� patients was better at predicting which patients should have adjuvant chemotherapy than the commonly-used method that follows recommendations from the American Society of Clinical Oncology (ASCO).

The researchers checked their findings against information from another set of colon cancer patients that had been published in the Journal of Clinical Oncology in 2005. Prof Tollenaar said: �In these stage II colon cancer patients, the five-year metastasis-free survival prediction was confirmed; for the good outcome group, five-year survival was 90% and for the poor outcome group it was 40%. This was important validation of our own results.�

From the genome-wide analysis, the researchers identified a subset of 100 genes that were able to predict outcome equally as well as the full-genome molecular expression profile. Many of these genes are know to regulate the Epithelial-Mesenchymal transition (EMT) � a programme of cell development that is thought to be a driving force behind the development of metastases in colorectal cancer.

Prof Tollenaar said that although his research predicted outcome of disease in patients who had not received adjuvant chemotherapy, more work would need to be done to identify the molecular profile for those patients who would actually benefit from chemotherapy.

Before the results of this research could start to be used in the clinic, Prof Tollenaar said two things needed to happen: �Current, ongoing validation studies required to confirm our findings have to be completed, and the test needs to be developed into a robust diagnostic device. The molecular profiling company Agendia BV of Amsterdam has taken this up and it is likely to be available in early 2008.�

As to whether these findings would save large numbers of colon cancer patients from unnecessary chemotherapy, Prof Tollenaar said: �This depends greatly on the current practice in different European countries. For example, in Spain 60% of stage II colon cancer patients receive adjuvant chemotherapy, while in The Netherlands only 20% do. So in some countries it will result in a decrease in the number of patients receiving chemotherapy and in others, an increase; but both outcomes will result in a more accurate selection of patients.�

Immune system modulation can halt liver failure in animals

Tue, 25 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Massachusetts General Hospital (MGH) researchers have a developed a totally new approach to treating liver failure � manipulating the immune response. If the results of the animal study can be applied in human patients, the approach may be able to keep patients alive until donor organs become available or to support liver function until the organ can regenerate itself, eliminating the need for a transplant. The findings are being reported in the journal PLOS One.

�We have identified a non-hepatic source of cells that can easily be expanded to the scale required for clinical application,� says Martin Yarmush, MD, PhD, director of the Center for Engineering in Medicine at MGH, the paper�s senior author. He also is the Helen Andrus Benedict Professor of Surgery and Bioengineering in the Harvard-MIT Division of Health Science and Technology (HST) and a senior scientific staff member at the Boston Shriners Burns Hospital.

The liver is one of the few major organs that is able to regenerate itself. But when the organ is damaged by diseases like chronic hepatitis, long-term alcohol consumption, or other causes, ongoing inflammation can increase cell death and suppress the natural regenerative process. The only current treatment for end-stage liver failure is transplantation, which is limited by the organ supply and requires long-term immunosuppressive treatment. While external liver assist devices have successfully supported some patients, such machines require a supply of preferably human liver cells, which have been difficult to acquire and expand.

For their investigation, the MGH research team used mesenchymal stem cells (MSCs) � cells from the bone marrow that develop into tissues supporting blood cell development in the marrow cavity. Previous research has shown that MSCs are able to inhibit several immune system activities. A supply of MSCs can be extracted from a patient�s own marrow and expanded to levels that could be therapeutically useful. To evaluate the ability of human MSCs to treat organ failure involving inflammatory activity, the investigators tested several ways of using the cells to treat rats in which liver failure had been induced.

Several approaches to administering MSCs reduced the biological signs of liver failure and improved the animals� survival. Although simply transplanting MSCs was not effective, two methods of delivering molecules secreted by the cells lessened inflammation within the liver and halted cell death. Cycling the blood of rats with liver failure through an external bioreactor containing MSCs also greatly reduced the metabolic signs of liver failure in the animals. Even more significantly, 71 percent of the rats treated with the MSC-seeded bioreactor survived, while only 14 percent of those in a control group were alive one week later.

�One essential function of MSCs in the bone marrow is to secrete molecules that promote the growth and maturation of blood cells,� say co-lead author Biju Parekkadan, an HST graduate student working in Yarmush�s lab. �We are now finding that these same molecules can be used as potent immunotherapeutics and envision a multi-tiered treatment of liver failure based on this work. A patient presenting with liver failure could first be treated with an intravenous injection of an �off-the-shelf� drug containing MSC-produced factors in an effort to halt cell damage and allow the organ to regenerate. If that is not effective, an MSC-based support device could be used as a bridge to transplantation or even as a long-term treatment.�

The researchers note that exactly how MSC-produced molecules inhibit the movement of immune cells into a damaged organ is not yet known and is currently under investigation. They also hope to examine the possibility of combining both MSCs and liver cells in a potential support device and to test the potential of MSCs to treat other immunological diseases.

Common abdominal pain may be due to a potentially treatable newly recognized inflammatory reaction

Wed, 19 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) JACKSONVILLE, Fla. -- As many as one in four people in westernized countries experience pain or discomfort in their upper abdomen, and physicians have almost nothing to offer except anti-acid medicines, which usually don�t work. Now, in a small but novel study, researchers have found evidence that an abnormal amount of inflammatory cells populates the upper intestine of affected individuals, which suggests a fresh way of understanding the common complaint.

The study, published in the September issue of Clinical Gastroenterology and Hepatology and conducted by researchers in the U.S., Sweden, England, and Australia, may also point to innovative methods to treat the condition and eliminate discomfort.

�Newly-designed, targeted anti-inflammatory medicine aimed at blocking the function of these cells might be very useful, if our results are validated,� says the study�s lead researcher, Nicholas J. Talley, M.D., Chair of Internal Medicine at Mayo Clinic in Jacksonville.

�We are quite intrigued by what we have discovered, because it probably represents a new disease entity, one that might be capable of diagnosis and management,� Dr. Talley says.

The scientists don�t know why inflammatory cells are present in one particular region of the small intestine, the duodenum that connects to the stomach, but they theorize that it could result from an allergic reaction to certain foods. Patients examined did not have infections, celiac disease (an autoimmune reaction to gluten protein), or cancer.

�I believe food intolerance can lead to motor and sensory abnormalities that are perceived as pain and discomfort,� Dr. Talley says. �But we have no evidence yet that this is definitely the case.�

To conduct the study, researchers in Sweden offered endoscopic examinations to 51 Swedish participants who complained of �nonulcer dyspepsia� as well as 49 randomly selected participants who had no pain. Dyspepsia is chronic or recurrent pain, or a feeling of abdominal fullness after eating or nausea, and the nonulcer form means there is not any structural abnormality such as an ulcer. For reasons that are not clear, sensitivity to stomach acid occurs in some of these patients, but acid suppression therapy does not work in two-thirds of patients who try it. There are really very few effective therapies, Dr. Talley says.

During the endoscopy procedure, physicians removed biopsy tissue from several places in the small intestine of participants, and the samples were examined by pathologists who did not know who the samples belonged to.

The researchers found significantly more eosinophil cells in people with nonulcer dyspepsia, compared to the control group population, but these cells were found only in the duodenum, the place in the intestine where most chemical digestion takes place. Eosinophils are white blood cells, part of the immune system, which fight parasites.

The researchers cannot yet say whether duodenal esoinophilia is the cause of the pain or an effect of another factor causing the disorder, although Dr. Talley says �a casual link remains our hypothesis.

�The presence of these cells has been overlooked because no one has used rigorous quantification methods before, and because biopsy examinations of the duodenum are not routinely performed,� he says. �Now we have a new direction to go in.�

Children's Hospital of Pittsburgh psychiatrist receives prestigious NIH award

Wed, 19 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Children�s Hospital of Pittsburgh of UPMC psychiatrist Eva M. Szigethy, MD, PhD, is among a select group of researchers who have been chosen by the director of the National Institutes of Health (NIH) to receive a prestigious New Innovator Award.

NIH director Elias A. Zerhouni, MD, announced today that 41 researchers from across the country � many of them in the early stages of their careers, including Dr. Szigethy � will receive five-year grants totaling more than $105 million. Dr. Szigethy is one of only 29 recipients of the NIH Director�s New Innovator Award (selected from more than 2,100 applicants), and there are 12 recipients of the Pioneer Award.

Pioneer Awards support scientists at any career stage, while New Innovator Awards are reserved for new investigators who have not received an NIH regular research or similar grant. This is the first group of New Innovator Awards and the fourth group of Pioneer Awards. Both programs are part of an NIH Roadmap for Medical Research initiative that tests new approaches to supporting novel research.

Dr. Szigethy is the medical director of the Coping Clinic, part of the Inflammatory Bowel Disease (IBD) Center at Children�s Hospital. She also is an assistant professor of psychiatry and pediatrics at the University of Pittsburgh School of Medicine. By working with young patients who have been diagnosed with Crohn�s disease or ulcerative colitis, Dr. Szigethy is investigating the interactions among the brain, gut and immune system in how adolescents cope with chronic disease. She will work with Robert Noll, PhD, chief of the Division of Developmental and Behavioral Pediatrics at Children�s, and Ronald Dahl, MD, the Staunton Professor of Psychiatry and Pediatrics at the University of Pittsburgh to coordinate this multi-faceted research effort.

�Novel ideas and new investigators are essential ingredients for scientific progress, and the creative scientists we recognize with NIH Director�s Pioneer Awards and NIH Director�s New Innovator Awards are well-positioned to make significant � and potentially transformative � discoveries in a variety of areas,� Dr. Zerhouni said in announcing the award recipients.

Dr. Szigethy�s NIH award will allow her to use functional magnetic resonance imaging to study regions of the brain responsible for emotional and cognitive processing in patients with IBD with and without depression. She also will study the relationship between depressive symptoms and brain, immune and gastrointestinal functioning, as well as the effectiveness of cognitive behavioral therapy in treating patients with IBD who are depressed. The integration of behavioral health into comprehensive medical care represents a paradigm shift within medicine in treating children with chronic physical illness.

�The early identification and treatment of depression in children and adolescents with chronic physical illness such as IBD is an understudied area. Given the significant risk of emotional and physical harm to physically ill adolescents who are depressed, the development and implementation of effective preventive interventions is crucial,� she said. �The early data from our research examining the effects of a cognitive behavioral therapy shows promising effects in improving depressive symptoms in adolescents with IBD.�

New research may lead to earlier diagnosis and treatment of primary biliary cirrhosis in families

Mon, 10 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) ROCHESTER, Minn. -- Mayo Clinic researchers have found that first-degree relatives (i.e., parents, siblings, children) of patients with primary biliary cirrhosis (PBC) are more likely to have the biomarker of the disease in their blood. Armed with this new information, physicians could screen and assess first-degree relatives of PBC patients with a simple blood test, enabling them to diagnose and treat more patients before the disease causes irreversible liver damage. These findings were published in this month�s issue of Hepatology.

PBC is a chronic liver disease that affects nearly 50,000 people (primarily women) in North America. In individuals who have PBC, the bile ducts are slowly destroyed, causing harmful substances to build up in the liver and sometimes resulting in irreversible scarring of liver tissue and liver failure. About half of PBC patients have no symptoms and are diagnosed following abnormal results of routine liver tests.

Anti-mitochondrial antibodies are the biomarker, or the substance that correlates with the risk or presence of a disease, for PBC. This study, the largest of its kind, tested for anti-mitochondrial antibodies in 306 first-degree relatives of adult PBC patients and 196 healthy adults. The prevalence in first-degree relatives was 13.1 percent, compared to 1 percent in the control group of healthy adults. Even greater prevalence was found in female relatives, with 20.7 percent of sisters, 15.1 percent of mothers and 9.8 percent of daughters having anti-mitochondrial antibodies in their blood. While testing positive for anti-mitochondrial antibodies does not always lead to a diagnosis of PBC, the presence of these antibodies indicates a predisposition to develop the illness, particularly in the context of family history of the disease.

�Most PBC patients have no symptoms, but early detection is important because timely treatment can slow the progression of the disease before liver failure occurs,� says Konstantinos Lazaridis, M.D., the study�s lead author and a hepatologist at Mayo Clinic. �Because collectively one in five sisters of a PBC patient has anti-mitochondrial antibodies in their blood, we think it is worthwhile to screen first-degree relatives, particularly those older than 40 years, for this biomarker. It is a simple, inexpensive blood test that could lead to earlier diagnosis and treatment -- and ultimately, better outcomes for PBC patients.�

According to Dr. Lazaridis, the study�s findings regarding anti-mitochondrial antibodies in PBC relatives could also be important to better understanding the known genetic predisposition to PBC. His research team plans to continue screening and monitoring first-degree relatives of PBC patients over many years to further examine these findings and to shed light on the cause of this disease.

Soy isoflavone may inhibit common gastrointestinal illness in infants

Thu, 06 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) The soy isoflavone genistin--at concentrations present in soy infant formula-- may reduce a baby�s susceptibility to rotavirus infections by as much as 74 percent, according to a University of Illinois study published in September�s Journal of Nutrition.

�Rotavirus is the primary cause of diarrhea in infants, affecting virtually all children before age five. In the United States, it mainly leads to dehydration, doctor�s visits, and parents missing work to care for sick children. In developing countries, though, rotavirus causes approximately 611,000 deaths each year,� said Sharon Donovan, the Melissa M. Noel Professor of Nutrition at the U of I.

Although rotavirus vaccines have recently become available, they are expensive and cannot be given to some infants, she said.

�It�s exciting to think that the isoflavones in soy formula could be a cost-effective nutritional approach to decreasing the incidence and severity of rotavirus infections, especially among children in developing countries who are most at risk,� said the scientist of her work with doctoral candidate Aline Andres, who conducted the experiments.

In the study, cells in culture were exposed to rotavirus in the absence or presence of soy isoflavones, biologically active compounds in soy that are thought to have health benefits. Soy contains a number of different forms of isoflavones, and all were tested individually and as the complete mixture present in infant formula.

�Genistin and the mixture significantly reduced rotavirus infectivity by 33 to 74 percent,� she said. �But when genistin was taken out of the mixture, anti-rotavirus activity was lost, suggesting that it is the active component in reducing infectivity.�

Donovan focused her investigation on the isoflavone concentrations present in soy formula. That was the concentration at which rotavirus inhibition began to occur and then leveled off, indicating that there�s an effective range, and beyond that, there is no additional inhibition or toxicity.

�We then exposed the cells to different concentrations of rotavirus. If an infant had a severe infection or was exposed to a lot of rotavirus, we wondered if the isoflavones would still be as effective,� she said.

The inhibition held up across a 16-fold range of rotavirus exposure. �Even at the highest concentration of rotavirus particles, genistin or the mix of isoflavones inhibited infectivity,� said Donovan.

Genistin appeared to diminish infectivity by inhibiting binding of the virus to tissue-culture cells, she said.

Donovan�s laboratory soon plans to begin studies with neonatal piglets, an excellent model for studying rotavirus infection and the nutritional effects of various components on the intestine.

�We�ll be interested to see if we have the same results when we work with young animals,� she said.

UVa researchers awarded $5.2 million for infectious disease research

Thu, 30 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Two University of Virginia School of Medicine researchers have been awarded grants from the National Institute of Allergy and Infectious Diseases to develop treatments and tests for some rapidly emerging trouble spots in the area of gastrointestinal diseases.

Under these cooperative agreement (U01) grants, one scientist plans to develop a single test to identify more than 20 different food and waterborne pathogens while the second will create a single treatment which could protect people from becoming infected with more than 20 potential pathogens.

These pathogens have become well known to the general public in recent years, most notably from cases of E. coli bacteria infecting the food supply. In 2006, three people died and hundreds more were sickened after eating E. coli contaminated spinach. Possibly the best known modern case of large-scale public infection occurred in Milwaukee, Wisconsin in 1993. That year, more than 400,000 residents were sickened by Cryptosporidium parvum, a parasite which infiltrated the city�s water supply. More than 100 people died as a direct result of being infected with the parasite.

�Detecting an outbreak of E. coli in the food supply or cryptosporidium in the water supply as quickly as possible is vital if we are going to ensure the safety of what we eat and drink,� says Dr. Eric Houpt, associate professor of medicine at the University of Virginia School of Medicine. �The challenge is developing one test for the most common pathogens as opposed to just one test for one pathogen.�

Houpt will lead the team of researchers in developing the test, which includes scientists from Michigan State University, the Commonwealth of Virginia Division of Consolidated Laboratory Services, Kilimanjaro Christian Medical Center in Tanzania and the private sector. The resulting diagnostic test could then be deployed to medical settings such as hospitals, clinics, or field sites.

Dr. Paul Hoffman, professor of medicine at the University of Virginia, is using his $2.6 million grant to develop second generation antiparasitic/antibacterial therapeutics to treat infections caused by Giardia, Cryptosporidium, Campylobacter, Entamoeba and Clostridium difficile.

�These are all very nasty parasites to pick up and for many people, especially people with weaker immune systems, they can prove fatal because of the debilitating diarrhea associated with infection,� Hoffman says.

Working with pharmaceutical companies and University of Virginia professor of chemistry Timothy Macdonald, Hoffman�s team plans to exploit a novel drug target common in parasites and certain bacteria by chemically modifying available drugs to improve their efficacy and expand the conditions they can treat.

�If we can put this medication in a single pill, we can prevent people from becoming ill from these parasites before they are exposed and treat them if they have been infected,� Hoffman says. �This could be used in preparation for a natural disaster where we know there will be parasitic outbreaks or in response to a bioterrorism event.�

Houpt and Hoffman are optimistic the test and the treatment could be ready for testing within three years.

Inhaling nitric oxide helps transplant success

Wed, 29 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) BIRMINGHAM, Ala. � Administering inhaled nitric oxide (NO) during surgery helps protect liver transplant patients from organ failure, according to a new study from researchers at the University of Alabama at Birmingham (UAB).

The colorless gas improves post-surgical liver function by minimizing reperfusion injury, an unwanted side effect of restoring blood flow swiftly to a donor organ moments after transplantation into the recipient, the study authors said.

The findings on inhaled NO were published in the most recent issue of the Journal of Clinical Investigation. Results from this small study are preliminary and must be confirmed through larger clinical trials, said Rakesh Patel, Ph.D., an associate professor in the UAB Department of Pathology and a co-lead author on the study.

Exactly how the inhaled NO improves organ function at the cellular and molecular level is still unknown, Patel said. What is clear from post-surgical data are the benefits of inhaled NO for transplant patients: decreased hospital length-of-stays, and improved blood-clotting and liver-enzyme activity in post-transplant tests.Inhaled NO was administered to study subjects through an anesthesia mask by UAB anesthesiologists during transplant surgery.

The trial was designed to be �blinded� and placebo-controlled, which means some patients got inhaled NO and others did not, and neither patients nor their surgeons knew who was getting the gas.

�We were pleasantly surprised at how good the inhaled NO patients performed after the results were gathered,� Patel said. He said the results also showed inhaled NO protects transplanted livers from a rise in hepatic cell death.NO can be toxic to humans if breathed at high doses without medical supervision. Doses administered to the Journal of Clinical Investigation study participants were about 80 ppm, which did not cause toxicity and even proved beneficial, Patel said.

A larger clinical trial of inhaled NO involving more patients is about to start up at UAB in conjunction with Seattle-based University of Washington and the U.S. Department of Veterans Affairs Puget Sound Health Care System.Since reperfusion injury is possible in a wide range donated organs, the hope is that inhaled NO holds promise for improving �results to other solid organ transplants, such as heart, lung, kidney and pancreas,� said Devon Eckhoff, M.D., chief of UAB�s liver transplant program and a professor in the Department of Surgery.

Clearly if more donor organs end up healthier after transplantation, then donor-organ shortages may see some relief. �The more organs that are made suitable for transplantation will decrease the wait time for organ transplant recipients and subsequently save lives,� Eckhoff said.

New cancer fighter may help ICU patients beat infections

Mon, 27 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) HSP 90 inhibitors, which are finding favor in fighting cancer, may also help battle overwhelming infection in intensive care patients, researchers say.

Studies in an animal model of sepsis, a major cause of ICU patient death, indicate HSP 90 inhibitors help degrade proteins perpetuating inflammation, says Dr. John D. Catravas, director of the Medical College of Georgia Vascular Biology Center.

Results include restored lung function, reduced blood vessel leakage, which can lead to dangerous swelling in the lungs, and fewer byproducts of inflammation such as white blood cells, MCG researchers report in the American Journal of Respiratory and Critical Care Medicine, a journal of the American Thoracic Society.

They already have begun looking at the impact of HSP 90 inhibitors on the function of other organs, such as the liver and kidneys, also typically impacted by sepsis.

�We would die without an inflammatory response, but unreined inflammation is bad,� says Dr. Catravas. That�s just what happens with overwhelming infection; inflammation, which helps the body eliminate invaders, essentially keeps working after invaders are gone and the new target is the body.

�These are proteins that initially are useful in combating an invading bacteria but then, in some of us that develop sepsis for reasons that are poorly understood, the inflammatory response is amplified and stays much longer than it should,� says Dr. Catravas, the paper�s corresponding author.

Heat shock proteins carry proteins where they are needed and fold them up nicely so they do the correct job. Dr. Catravas compares their two-protein configuration to a lobster with its claws closed while tending to �client� proteins.

�The hypothesis we worked on is that these HSP 90 inhibitors take the heat shock protein and move it into a different conformation,� says Dr. Catravas. The published research indicates they were correct and that inhibitors, fortunately, readily target proteins that no longer have a useful function.

�The HSP 90 inhibitor binds to a little pocket in the dimer, the two identical proteins that make up HSP 90 complex, and forces the two claws open,� he says. �As soon as they open, as soon as the three-dimensional conformation of the HSP dimer and the client protein change, other proteins start attaching to the complex.� The client protein then becomes susceptible to degradation. It was their earlier finding that inducible nitric oxide synthase, a major mediator of sepsis, is a client protein of HSP 90 that led to the inhibitor study.

For the study, researchers used what would be considered lethal doses of endotoxin to create a worse-case infection and pretreated animals with smaller doses of HSP 90 than those currently under study for a wide range of cancers.

They have begun looking at more clinically relevant infection levels and identifying the best time after the insult to give the lowest dose. However, Dr. Catravas has not ruled out HSP 90 inhibitors� potential to preventively treat patients at risk because patients seem to tolerate it well in the cancer clinical trials.

He hopes to move ahead soon with clinical trials of HSP 90 inhibitors, used in conjunction with antibiotics, in intensive care patients.

These manmade HSP 90 inhibitors work by attaching where the protein pair�s energy source, called ATP, should be. The body appears to have an endogenous version, ADP, which has one less phosphate than ATP and binds at the same site, also opening the protein claws and sending the client protein toward degradation.

Gastric bypass reduces mortality risk in severely obese patients

Wed, 22 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Salt Lake City�Severely obese patients who undergo gastric bypass surgery significantly reduce their risk of death from coronary heart disease, diabetes, and cancer, according to research published in the Aug. 23, 2007, issue of The New England Journal of Medicine. The study was led by a team of researchers from the University of Utah School of Medicine and LDS Hospital.

The 14-year study evaluated 15,850 severely obese patients, half of whom underwent gastric bypass surgery to reduce their weight. The mortality rate from coronary heart disease was 56 percent lower in the surgery group than in the non-surgery (control) group. The surgery group also showed a 60 percent lower death rate from cancer and a 92 percent lower death from diabetes than the non-surgery group, according to Ted D. Adams, Ph.D., M.P.H., the study�s lead author,

Adams is a professor in the Division of Cardiovascular Genetics at the University of Utah School of Medicine and co-founder of the Intermountain Health and Fitness Institute at LDS Hospital in Salt Lake City.

While mortality rates for specific diseases were lower in the surgery group, Adams said mortality rates from other causes � such as accidents and suicide � were 58 percent higher among those who had the weight loss surgery than the control group.

�This study helps to further define the effects of gastric bypass surgery on long-term mortality. Reduction in death by any cause, and disease-specific deaths such as coronary heart disease, diabetes, and cancer were significantly reduced in surgery patients compared to the non-surgical control group,� he said. �However, rates of death not caused by disease were shown to be greater in those who underwent the weight-loss surgery when compared to controls.�

The paper suggests at least some of these non-disease deaths in the surgery group may be due to unrecognized pre-surgical mood disorders or post-traumatic stress disorders, which appear to be more common in severely obese patients. Adams said the research shows the need for better methods of evaluating candidates for the surgery, including the possible need for psychological evaluation and psychiatric treatment before surgery, and aggressive follow-up after surgery.

The reduced mortality for any cause of death is likely related to significant health improvements that follow gastric bypass surgery, such as reduced blood pressure, improved or resolved diabetes, and reduced sleep apnea, says Adams.

Women accounted for 84 percent of the patients involved in the study.

The average body mass index (BMI), which is calculated by dividing a person�s weight in kilograms by the square of the person�s height, for patients in the surgery group was 45.3, and 46.7 for the non-surgery group.

Age alone does not increase risk of death following liver transplant among selected septuagenarians

Mon, 20 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Advanced age alone does not appear to be associated with the risk of death following liver transplant, according to a report in the August issue of Archives of Surgery, one of the JAMA/Archives journals.

Life expectancy has increased in recent years, with individuals older than 70 representing a large and fast-growing segment of the general population, according to background information in the article. A healthy 70-year-old adult living in a developed country with a nutritious diet and good medical care can expect to live to age 80 or 90. �As longevity has increased, the burden of liver disease in patients of advancing age has also increased and is associated with a higher mortality than in younger adults,� the authors write. �In the 1980s, the death rate from chronic liver disease was highest in patients 65 to 74 years of age. This has led to more older patients undergoing liver transplantation.�

Gerald S. Lipshutz, M.D., M.S., and colleagues at the David Geffen School of Medicine at UCLA reviewed the records of patients who received their first liver transplant between 1988 and 2005. They compared 62 patients who were age 70 or older (average age 71.9) to 864 patients age age 50 to 59 (average age 54.3). Survival time was measured until death, the last known follow-up date or retransplantation.

Overall, 31 of 62 patients age 70 or older and 345 of 864 patients younger than 70 died during the study period. After one year, 73.3 percent of older patients and 79.4 percent of younger patients survived; after ten years, 39.7 percent of older patients and 45.2 percent of younger patients were still alive. �We found no statistically significant difference in survival in the first 10 years after transplantation for a group of 62 patients 70 years or older when compared with a younger cohort of 864 recipients aged 50 to 59 years with similar characteristics,� the authors write. �The longest-surviving patient was 88 years old at 15 years after transplantation. One-year unadjusted survival of septuagenarians in the most recent surgical period, 2001 to 2005, was 94.4 percent.�

The researchers also analyzed 26 variables related to the recipients, donors and transplant operations to see which predicted patient deaths. Of the 26, four were associated with death rates: preoperative hospitalization, prolonged period of cold storage between liver removal and transplantation, cirrhosis caused by hepatitis C and alcohol and an increasing model for end-stage liver disease (MELD) score, a measure of disease severity. An age of 70 years or older did not independently predict death in transplant patients.

�In conclusion, biological and physiological variables may play a more important role than advanced age in predicting poor survival after liver transplantation. Measures of physiological age and risk of complications should be used in the evaluation process of elderly transplant candidates,� the authors conclude. �Age by itself should not be used to limit liver transplantation.�

Metabolic study in mice could lead to 'good cholesterol' boosters

Tue, 07 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers have identified a new player in the control of so-called good cholesterol that circulates in the bloodstream and reduces heart attack risk, according to a report in the August issue of Cell Metabolism, a publication of Cell Press. Should the metabolic pathway uncovered in mice operate similarly in humans, the new discovery could point the way to therapies that protect against heart disease by boosting concentrations of the beneficial high-density lipoprotein cholesterol (HDL-C).

By and large, the medicines now available lower levels of the bad low-density lipoprotein cholesterol [LDL-C], said Weijun Jin of the University of Pennsylvania School of Medicine. There is a great need for methods to raise good cholesterol levels. Our findings suggest there may be multiple places to interrupt the metabolism of HDL-C.

LDL-C can build up in blood vessel walls, increasing the risk of heart disease or stroke. By contrast, HDL-C tends to carry cholesterol away from the arteries to the livera process known as reverse cholesterol transportwhere it is broken down and then eliminated from the body.

Existing LDL-C-lowering drugs such as statins can reduce the risk of heart attack by 20 to 35 percent, Jin said. However, treatment methods that would simultaneously lower bad cholesterol and increase good cholesterol have the potential to work even better. Indeed, researchers believe that increasing HDL-C while lowering LDL-C might cut heart attack risk by as much as 70 percent, he explained.

In the current study, the researchers found that treatments that partially block the activity of liver enzymes called proprotein convertases decreased plasma HDL-C levels in mice. They showed that the metabolic effect of the proprotein convertases depended on yet another factor, an enzyme called endothelial lipase (EL), which breaks down HDL-C. Proprotein convertases normally reduce EL function, they reported. Thus, the loss of proprotein convertase activity leads to an increase in EL and a decline in HDL-C.

Likewise, they showed that increased activity of proprotein convertases in the liver gives a significant boost to the protective HDL-C.

Proprotein convertases are an unexpected new player in HDL-C metabolism, Jin said. By manipulating levels of the enzyme in both directions, we were able to reduce HDL-C to almost nothing or double it. That wide range of effects suggests that it may be theoretically possible to manipulate good cholesterol levels to whatever point you like.

He emphasized, however, that the new findings represent basic research in animals. Further investigation will examine to what extent the pathway is preserved in humans, Jin said. The authors will also look for chemicals capable of modifying the pathway, which could hold promise as new good-cholesterol-boosting drugs.

Does this child have appendicitis? Watch out for key signs

Thu, 02 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) A 5-year-old with abdominal pain, nausea and fever may have appendicitis or any of a number of other problems. But how does the childs doctor decide whether to schedule an emergency appendectomy to surgically remove a presumably inflamed appendix a procedure that carries its own risks like any surgery or wait and observe what could be a ticking time bomb that could rupture and kill the patient in a matter of hours Its a classic physicians dilemma, but a new study led by the Johns Hopkins Childrens Center may ease the pediatricians problem-solving and parents anxiety.

Reporting on their review of the frequency of the most common symptoms of actual appendicitis in children, the researchers concluded that beyond fever, the most telltale signs are rebound tenderness or pain that occurs after pressure is removed abruptly from the lower right part of the abdomen; abdominal pain that starts around the belly button and migrates down and to the right; and an elevated white blood cell count (10,000 or more per microliter), which is a marker of infection in the body.

Notably, loss of appetite, nausea and vomiting, hallmark appendicitis symptoms in adults, were NOT predictive of appendicitis in children.

These signs dont give you an absolute diagnosis, but they should prompt the doctor to refer the child to a surgeon for evaluation, said study lead author David Bundy, M.D., M.P.H., a pediatrician at the Johns Hopkins Childrens Center.

Appendicitis is most common in teens and young adults in their early 20s. However, children younger than 4 years are at the highest risk for a rupture. Up to 80 percent of appendicitis cases in this age group end in rupture, partly because young children have fewer of the classic symptoms of nausea, vomiting and pain localized in the lower right portion of the abdomen than do teenagers and young adults, making the diagnosis easy to miss or delay.In the study report, published in the July 25 issue of the Journal of the American Medical Association, the researchers said ultrasound and CT scan images can be helpful, but are not always conclusive, even if they are available on an emergency basis. And CT scans in particular expose young children to radiation, which should be avoided if possible.

In a very young child, the presentation of symptoms associated with appendicitis tends to be different from adults, so when trying to decide between fast-track surgery versus watchful observation, youre often damned if you do and damned if you dont, Bundy said. In our analysis, weve identified some of the more powerful telltale signs that should help residents, general pediatricians and ER doctors narrow down what is seldom a clear-cut diagnosis.

The appendix is a small tube extending from the large intestine, and infections and inflammation of the organ can be dangerous. The only absolute way to diagnose the condition is surgery, and each year, appendicitis sends 77,000 American children to the hospital. An estimated one-third of them suffer a ruptured appendix, a life-threatening complication, before they reach the OR.

In their analysis of previous research, investigators searched hundreds of studies, weeding out weak from solid science. The 25 studies that made the final cut examined symptoms and outcomes in children who presented with abdominal pain and in whom appendicitis was considered a possible diagnosis. Abdominal pain in children is one of the most common and vaguest symptoms, and can suggest anything from innocent constipation to serious infections or blockages of the intestines. Doctors advise parents that any abdominal pain should be evaluated for appendicitis. We really want parents to keep in mind that children with appendicitis dont always show up with the classic story that we see in adults, Bundy says. There isnt a perfect formula, but we think the signs weve identified can help.

Study shows radiofrequency ablation highly effective in treating kidney tumors

Wed, 01 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) The patients underwent CT-guided radiofrequency ablation (RFA) at Wake Forest Baptist for kidney tumors ranging in size from 0.6 cm to 8.8 cm. A total of 125 tumors in 104 patients were treated over the period 2000 to 2006. In all of the patients, a biopsy had confirmed the presence of renal cell carcinomas (RCC), a common type of renal malignancy.

Of 95 tumors that were smaller than 3.7 cm (about 1.5 in.), all were completely eradicated by a single treatment, along with 14 of the larger tumors. Seven more of the 16 remaining larger tumors were eradicated after a second treatment, for a total 93 percent success rate for all 125 tumors. The results, reported in the August issue of the American Journal of Roentgenology, were based on follow-up exams over an average of about 14 months.

This is the largest treatment group to date of patients with biopsy-proven renal malignancies, said Ronald J. Zagoria, M.D., a professor of radiology at Wake Forest Baptist, an associate in urologic surgery, and lead author on the study. The results a high cure rate and low complication rate establish that at institutions with experience doing this procedure, this is an alternative method for treating small renal malignancies in patients who are not good surgical candidates.

RFA uses a needle-like treatment probe, guided by computed tomography (CT) as it is inserted through the skin into the tumor. The probes high-frequency alternating current heats the tumor tissue and destroys it. The technique has been used successfully in liver tumors since the early 1990s and has more recently been adapted for treatment of RCC.

Renal cell carcinomas that are smaller than 3.7 cm in diameter can be reliably and safely eradicated with percutaneous RFA, Zagoria and his colleagues conclude in the report. This result is regardless of the location or position of the RCC in the kidney. Larger tumors can also be eradicated with percutaneous RFA, they say, but with the larger tumors the risk of incomplete tumor destruction increases substantially. The authors also note that larger tumors near the middle of the kidney may be more difficult to ablate, possibly because they are close to large blood vessels or the ureter.

RFA is an outpatient procedure in which the patient is sedated but conscious and a local anesthetic is used at the puncture site. In the study being reported, 101 of the 104 patients went home the same day, and three were hospitalized after the procedure one for a planned treatment, another for treatment of bruising around the puncture, and a third for treatment of exacerbation of a heart condition.

A total of eight patients experienced complications, including temporary air pockets in the chest cavity, mild to severe pain after the procedure, pneumonia, and problems with their ureters. Generally, the report says, this study shows that the procedure ... has a very low rate of complications. Standard treatment for RCC has been a removal of the affected kidney, along with adjoining blood vessels and lymph nodes, known as a radical nephrectomy, although newer minimally invasive techniques, such as laparoscopic surgery, have also been used successfully.

Zagoria cautioned that RFA is not recommended if patients are good surgical candidates who are healthy, younger, and have two normal kidneys, because long-term follow-up is lacking and therefore the durability of cure is not confirmed. (The average age of patients in the study was about 70, with a range of 30-89.) However, he said, I think this is a big advance in treating renal tumors. The best candidates for RFA, he said, are patients with increased risk of complications from surgery and those with an hereditary condition that makes it likely they will require repeated treatments because of continual development of RCCs.

Method shows promise for early detection of pancreatic cancer

Wed, 01 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) EVANSTON, Ill. --- Optical technology developed by a Northwestern University biomedical engineer shown to be effective in the early detection of colon cancer now appears promising for detecting pancreatic cancer, the fourth most common cause of cancer deaths in the United States.

Known as a silent killer, with no method of early detection, pancreatic cancer spreads rapidly and seldom is detected in its early stages. The new technique could lead to the first screening method for pancreatic cancer in asymptomatic patients, said Vadim Backman, developer of the technology and professor of biomedical engineering at Northwesterns Robert R. McCormick School of Engineering and Applied Science.

Backman and Yang Liu, a former graduate student of Backmans, teamed up with physicians at Evanston Northwestern Healthcare (ENH) to test the technique in a pilot study of 51 patients. The researchers found they could detect both early- and advanced-stage pancreatic cancer without touching or imaging the pancreas.

The extraordinarily sensitive technique, which is minimally invasive and takes advantage of certain light-scattering effects, can detect abnormal changes in cells lining the duodenum even though the cells appear normal when examined with a conventional microscope. The results, which will be published in the Aug. 1 issue of the journal Clinical Cancer Research, show that the changes accurately predict the presence of cancer.

More than 30,000 people in the United States die each year from pancreatic cancer. Count Basie, René Magritte, Billy Carter and Joseph Cardinal Bernardin all died from it; Luciano Pavarotti is fighting the disease. The overall five-year survival rate is less than 5 percent; most patients die within the first two years. If detected early, when the tumor can be successfully removed, however, the survival rate is 100 percent if a precancerous lesion is found and 50 percent for a stage 1 cancer.

Using endoscopy and taking biopsies of the pancreas are extremely risky procedures that are not used on asymptomatic patients, said Backman. When a patient becomes symptomatic, it is too late. This creates a vicious cycle that we want to break.

We have found that we can take measurements safely in the duodenum and use a biological phenomenon called the field effect to our advantage, he said. If you have a precancerous or cancerous lesion in the pancreas, even tissue that looks normal and is away from the lesion -- including in the duodenum, a different organ than the pancreas -- will have molecular and other kinds of abnormal changes. No one can detect these changes earlier than we can.

To test the effectiveness of the technology in screening for pancreatic cancer, Backman and Liu have been collaborating with Randall E. Brand, M.D., a gastroenterologist with Evanston Northwestern Healthcare who specializes in pancreatic cancer and is an associate professor of medicine at Northwesterns Feinberg School of Medicine. They have shown that they can detect changes in the duodenal tissue and that these optical markers predict the presence of cancer.

The researchers found that the same optical markers that were significant in earlier colon cancer studies at ENH using Backmans technology proved also to be significant for pancreatic cancer. An optical marker is a signature at the sub-micro level that shows changes in tissue due to the presence of a precancerous lesion or cancer.

Scientists find why red beans and rice can be nauseating

Wed, 01 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) People cry foul when fowl is undercooked, but what about red beans and rice

Scientists have discovered how lectins, a family of proteins believed to be a natural insecticide that is abundant in undercooked legumes and grains, can make you feel temporarily miserable.

Its known that it can be a toxin, Dr. Paul L. McNeil, cell biologist at the Medical College of Georgia, says of the lectin protein thats commonly found in vegetables. Lectins, which bind strongly to carbohydrates that decorate cell surfaces, have a particular affinity for the heavy-carbohydrate coats of epithelial cells that line the gastrointestinal tract.

Researchers have long known that ingesting too much undercooked lectin can cause nausea, diarrhea and vomiting. What they didnt know was how lectin caused food poisoning.

Work published Aug. 1 in PloS One shows lectins disable GI tract cells, which are constantly bombarded while digesting food, from repairing tears in cells walls from all the activity. Repair normally occurs in seconds: internal membranes move up to patch the tear, the cell recovers and the one-cell layer lining of the GI tract remains intact.

If those individual cells cannot repair tears, they die, says Dr. McNeil. That means you have gaps in the integrity of the surface area of the epithelium and you are exposing the nasty internal world of your GI tract to your blood supply.

The epithelial lining is a continuous, natural barrier between digesting food in the GI tract and the blood supply. When intact, it allows only good stuff like nutrients to pass through.

Your body senses that lack of barrier function and tells you to eliminate the entire contents of the GI tract, says Dr. McNeil, noting that lectins apparent role as a natural insecticide and as a source of food poisoning are related. If you get vomiting and diarrhea you are going to eliminate the entire contents of your gastrointestinal tract, right And, you are not going to eat red beans again the next day, right That is probably the point if they are natural insecticides. Alcohol will do the same thing. When you drink too much alcohol, you can destroy the lining of your stomach.

But the scientist who first identified how injured cells patch themselves says lectin blocks this repair mechanism better than anything else hes seen. Interestingly, he and his colleagues showed in PloS Biology in 2006 how roughage which includes beans help people stay regular by causing more cell tears, which enables more mucus to escape from cells, essentially greasing the GI tract.

That same research team, which includes Dr. Katsuya Miyake, MCG cell biologist, and Dr. Toru Tanaka, pharmacologist at Josai University in Japan, has now shown lectin is also very good at blocking mucus expulsion from cells.

In fact, they discovered lectins role in stopping cell-patching and mucus release while researching roughage. The multipurpose lectin is a powerful stain the team used to look at mucus released by cells after tearing. They found if they used too much lectin there was no patching or mucus, just cell death.

Biologically its interesting because it might tell us more about the mechanism of repair, says Dr. McNeil, who wants to learn more about how lectin interferes with repair. We know the mechanism involves surface binding because you can add lectin and the cells cant repair. You take the same culture of cells, wash the lectin away, injure other cells in the culture and they repair fine. We also know its a very rapid, surface-initiated inhibition.

In addition to the immediate discomfort undercooked beans and rice can cause, long term concerns ingestion of lectin has also been linked to colorectal cancer and celiac disease, a common problem in which individuals are sensitive to gluten, a mixture of proteins derived from wheat flour that includes lectins. The small intestine of the celiac sufferer is unable to properly absorb nutrients after gluten ingestion.

Oddly, in a laboratory dish, safe from mechanical stresses that cause surface tears, lectin can make cells divide, which is quite the opposite of making cells sick, Dr. McNeil says. A recent Science paper implicated lectin in diabetes as well.

Its possible that this bioactive property of lectin that binds to our cells could have long-term consequences taken even in small amounts, he says, noting that thorough cooking destroys most but not all lectin. Maybe the bloating and gas is telling us something about lectin when its just a minor irritation.

He notes lectin is easily among the top-10 causes of food poisoning but is unlikely to be lethal because the body is so good at sensing the break in the GI barrier and eliminating the problem.

Molecule blocks gene, sheds light on liver cancer

Wed, 01 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) COLUMBUS , Ohio New research shows how a particular small molecule blocks the activity of a cancer-suppressing gene, allowing liver-cancer cells to grow and spread.

This molecule is a microRNA, a recently discovered class of tiny molecules used by cells to help control the kinds and amounts of proteins they make. More than 250 different microRNAs have been discovered, and several have been linked to cancer.

These findings show exactly how one specific microRNA, called miR-21, helps cancer develop.

This molecule occurs at unusually high levels in many kinds of cancer cells. The study looked at a gene called PTEN (pronounced P-TEN), which normally protects cells from becoming cancerous. Researchers know that the abnormal silencing of this tumor-suppressor gene contributes to the development of liver cancer and other malignancies.

The findings help explain how liver cancer develops and may identify new drug targets for treating the disease. This particular microRNA might also provide a marker to help determine a patient's prognosis.

The study, led by researchers at the Ohio State University Comprehensive Cancer Center, is published in the August issue of the journal Gastroenterology.

Our findings essentially describe a new mechanism used by cells to regulate PTEN, says principal investigator Tushar Patel, professor of internal medicine, director of hepatology and a liver-cancer specialist at Ohio State University Medical Center.

They show that high levels of miR-21 block the PTEN gene, he explained. This, in turn, activates chemical pathways that enable cancer cells to proliferate, migrate and invade other tissues, all of which are features of tumor formation.

Patel and his collaborators began the study by measuring the relative levels of 197 microRNAs in normal liver cells and in liver cancer cells from human tumors and in four liver cancer cell lines.

Levels of miR-21 were up to nine times greater in liver-tumor tissue compared with normal liver tissue, twice that of the next highest microRNA.

Earlier research led by Patel had shown that miR-21 probably targeted PTEN, and this study confirmed that.

Furthermore, the researchers showed that adding high levels of miR-21 to normal liver cells caused PTEN levels to drop. They also traced the chemical pathways that increased the cells' abilities to proliferate, migrate and invade other tissues.

Our findings indicate that miR-21 plays a fundamental role in tumor-cell behavior and cancer development, Patel says, and this may also be relevant to other tumors in which miR-21 is overexpressed. If this work is reproduced in investigations of other cancers, it could be a big step forward, he says.