RxPG News : Gastroenterology

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

Sat, 06 Feb 2010 12:58:24 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 04:59:36 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 03:59:36 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 03:59:36 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 03:59:36 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 03:59:36 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 03:59:36 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 04:59:36 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 08:13:03 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 04:59:37 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 14:12:21 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 03:59:37 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 23:52:06 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 03:59:37 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 03:59:37 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 09:07:20 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 19:54:57 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 03:59:37 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 03:59:37 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 04:59:37 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 04:59:37 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 08:02:46 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 07:08:44 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 06:52:36 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 04:59:37 PST

Do patients with inflammatory bowel disease receive optimal care?

Fri, 22 Feb 2008 04:59:37 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 04:59:37 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 04:59:37 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 04:59:37 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 20:54:37 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 04:59:37 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 13:48:08 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 04:59:37 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 04:59:37 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 04:59:37 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 04:59:37 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 04:59:37 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 04:59:37 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 04:59:37 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 04:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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 03:59:37 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.

Gene identified for Crohn's disease in children

Wed, 18 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Pediatrics researchers have identified a gene variant that raises a childs risk of Crohns disease, a chronic and painful condition attributed to inflammation of the gastrointestinal tract.

The research reinforces previous results by German researchers, who found the same gene variant associated with the adult form of Crohns disease.

Researchers from The Childrens Hospital of Philadelphia and The University of Pennsylvania reported their results in a letter in the August issue of the journal Gut.

Because Crohns disease is complex, with multiple genes interacting with each other and with environmental factors, its important to sort out specific genes and to replicate previous findings, said the studys first author, Robert N. Baldassano, M.D., director of the Center for Pediatric Inflammatory Bowel Disease at Childrens Hospital. There are different types of Crohns disease, so classifying types by genetic profiles may help us select the most appropriate treatments for each patient.

The study compared the genomes of 143 children with Crohns disease to genomes of 282 matched control subjects. The study team found that 64 percent of children with Crohns disease had a specific variant form of the gene ATG16L1, compared with 52 percent of the healthy children. The odds ratio for children with the gene variant was 1.62 compared to control children, meaning that those who have the variant were 62 percent more likely to have Crohns disease than children with the more common allele.

A separate test that analyzed trios (a Crohns patient and both parents) also found an association between the ATG16L1 gene variant and disease symptoms. This finding strengthened the results of the pediatric case-control study.

The genome-wide association study, which used highly automated analytic equipment to scan each patients DNA for more than half a million genetic markers, was performed at the Center for Applied Genomics at Childrens Hospital. The Centers tools spell out a patients genotypethe specific pattern of variations among an individuals 30,000 genes. Established in the summer of 2006, the center is taking on one of the largest genotyping projects in the world, and is the largest one dedicated to genetic analysis of childhood diseases.

This study is among the first that our center has published on a gene associated with a complex childhood disease, but we have many projects under way, said senior author Hakon Hakonarson, M.D., Ph.D., the director of the Center for Applied Genomics. Our goal at the Center is to discover the major disease-causing variants and genes that influence complex pediatric diseases, thus providing a scientific foundation for translating those discoveries into successful treatments. Earlier this month, Hakonarson collaborated with researchers in Montreal to identify a gene associated with insulin-dependent diabetes in children. Other projects at the Center are seeking genes associated with pediatric asthma, allergy, obesity, attention-deficit hyperactivity disorder, autism, hypertension, juvenile rheumatoid arthritis and the pediatric cancer neuroblastoma.

The gene implicated in the current research, ATG16L1, plays an important role in the autophagosome pathway, a sequence of biological events involved in processing bacteria within cells. While the mechanisms are not fully understood, said Baldassano, a mutation in the gene may weaken a cells ability to degrade cellular waste products, including bacteria. When unprocessed waste products pile up within the cell, they may stimulate the inflammatory response that characterizes Crohns disease.

Although much research remains to be done, he added, better understanding of the disease process may guide doctors to new and improved therapies. If an excess of bacteria is the problem, we may find antibiotics effective in treating this type of Crohns disease. Other approaches may be to use immune-boosting drugs to blunt the inflammation, or determining whether particular foods interact with genetic susceptibilities to affect disease symptoms. Understanding gene influences gives us a more targeted way to look at disease physiology, and also may suggest targets for treatment. Baldassano and Hakonarson said that they will continue to search for other gene variants associated with Crohns disease and the closely related bowel disorder ulcerative colitis.

Research shows new therapy is effective for patients with Crohn's disease

Wed, 18 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Rochester, Minn. -- Mayo Clinic researchers have found that Certolizumab pegol is an effective treatment for adults with Crohns disease, according to two new studies. These findings were published in todays issue of the New England Journal of Medicine. Certolizumab pegol blocks tumor necrosis factor, an important cause of inflammation in Crohns disease.

Crohns disease is an inflammatory disorder of the gastrointestinal tract that affects an estimated 500,000 people in the United States. Symptoms include abdominal pain, fever, nausea, vomiting, weight loss and diarrhea. Crohns disease has no known medical cure. Currently approved therapies that also block tumor necrosis factor include intravenous infusions of infliximab or subcutaneous injections of adalimumab.

Many patients with Crohns disease who receive repeated administration of infliximab or adalimumab will eventually stop responding to the therapy, says William Sandborn, M.D., a study author and gastroenterologist at Mayo Clinic. Therefore, it is important to have a variety of options in this drug class to help patients avoid Crohns disease symptoms over longer periods of time.

According to Dr. Sandborn, the dosing regimen for certolizumab pegol is more patient-friendly than infliximab or adalimumab, with less frequent subcutaneous injections that can be self-administered.

The first study, led by Dr. Sandborn, set out to determine if certolizumab pegol was effective in easing the symptoms of patients with active Crohns disease. The study involved 662 adult patients with moderate to severe Crohns disease, and represents a unique trial design in Crohns disease. This is the first double-blind, placebo-controlled trial in which a drug that blocks tumor necrosis factor has been evaluated beyond 12 weeks in the treatment of Crohns disease. Researchers found that 35 percent of patients who received certolizumab pegol achieved an improvement in their clinical symptoms after six weeks, while 27 percent of patients who received a placebo experienced improved symptoms in the same period. Likewise, after six months, 37 percent of patients who received certolizumab pegol achieved an improvement in their clinical symptoms, compared to 27 percent of patients who received a placebo.

The second study set out to determine if certolizumab pegol was effective as a long-term maintenance therapy for patients with Crohns disease. It involved 668 patients, of whom 428 (64 percent), responded, or achieved an improvement in their clinical symptoms, after taking certolizumab pegol for six weeks. The response was maintained for six months in 63 percent of patients receiving certolizumab pegol, while 36 percent of patients who received a placebo from week six to six months experienced improved symptoms in that period. Additionally, clinical remission from symptoms was achieved in 48 percent of patients in the certolizumab pegol group, compared to 29 percent of those in the placebo group.

Certolizumab pegol is not yet approved by the Food and Drug Administration (FDA). One side effect of certolizumab pegol that was observed during the studies, and is seen in other drugs that block tumor necrosis factor, was a small increase in the risk for serious infection, including one case of pulmonary tuberculosis. However, injection-site reactions were very low and patients experienced low rates of antinuclear antibodies, which can occasionally cause lupus-like symptoms when elevated.

Approximately 25 percent of the patients in these studies had previously been treated with infliximab therapy and had lost response, says Dr. Sandborn. These studies show that certolizumab pegol could be a new option to treat patients with Crohns disease, both those who have never been treated before, and those who have lost response to other therapies. Upon FDA approval, the use of certolizumab pegol could significantly improve quality of life for many patients with Crohns disease.

Antibody retards growth and induces death in liver cancer cells

Wed, 11 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) PITTBURGH, July 11 Researchers from the University of Pittsburgh School of Medicine report a significant new advance in the search for an effective treatment for human liver cancer in the July issue of Molecular Cancer Therapeutics. Using a newly available monoclonal antibody, they demonstrated significant reductions in tumor cell proliferation and survival in human and mouse hepatocellular cancer (HCC) cell lines. According to the researchers, this finding has significant implications not only for the treatment of liver cancer but for a number of different types of cancer.

Most cases of HCC are secondary to either a viral hepatitis infection or cirrhosis of the liver. Despite recent advances, it remains a disease of grim prognosis due to the poorly understood mechanism of how the disease originates and spreads. Most patients live only a short time after diagnosis.

Based on previous studies showing that some pathways that were previously thought to be active only during fetal liver development, particularly the class III receptor tyrosine kinase (RTK) family pathway, became highly active again in the liver of HCC patients, Satdarshan P. Singh Monga, M.D., associate professor, division of cellular and molecular pathology and colleagues at the University of Pittsburgh School of Medicine, obtained rat and human liver cancer cell lines and analyzed them for level of expression of an RTK protein known as platelet-derived growth factor receptor-alpha, or PDGFRá. The investigators also analyzed the cells for their level of activation of the PDGFRá gene.

At an early fetal stage of liver development in the mouse, the investigators found that the level of expression of PDGFRá was 37 times higher compared to later stages of development in the adult mouse liver. They also found significantly higher levels of PDGFRá in rat and human liver cancer cell lines as compared to normal cells in culture.

Dr. Mongas group then treated human and mouse liver cancer cell lines with a monoclonal antibody targeted against PDGFRá. It resulted in a significant decrease in tumor cell proliferation and a marked increase in tumor cell death. In fact, all tumor cell lines experienced significant decreases in proliferation in response to the monoclonal antibody and there was a 4- to 18-fold increase in programmed cell death, or apoptosis, among the cancer cell lines compared to normal control cells.

According to Dr. Monga, these results suggest that PDGFRá offers an important new therapeutic target for the treatment of HCC.

We are very excited because this is the first targeted therapy for liver cancer. Other therapies have some modest benefits, but no one knows exactly how they work. We now have identified a pathway that appears to be overly active in more than 70 percent of the cancers we examined and, when targeted, leads to significant reduction in tumor cell proliferation and survival, said Dr. Monga.

More importantly, targeting the PDGFRá pathway in liver cancer cells does not appear to affect normal liver cells, making the treatment relatively non-toxic. Normally, regenerating liver cells are not exclusively dependent on this pathway, and it is not overly active in other types of cells. So this monoclonal antibody is a highly targeted treatment for this disease, he added.

Furthermore, because high expression of PDGFRá has been detected in a variety of tumors, such as skin cancer, brain tumors, gastrointestinal tumors, prostate tumors, ovarian cancer and leukemia, Dr. Monga believes these findings could have much broader applications.

U-M, Israeli scientists report major advance in search for genes associated with colon cancer

Sun, 08 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) ANN ARBOR, Mich. - A 10-year study involving thousands of Israeli Jews and Arabs, led by researchers from American and Israeli institutions, has yielded important new information in the search for the genes that make a person more likely to develop colon cancer.

In a paper to be published in the July issue of Cancer Biology and Therapy, the international research team reports finding a significant link between genetic variation in a single region of human chromosome 8 and the risk of colorectal cancer.

The link was found by detailed comparisons of genetic material from thousands of colon cancer patients and non-patients, and by evaluating the incidence of colon cancer among the immediate family members of colon cancer patients.

In all, people who carry the specific genetic variation, called a marker, were found to be 23 percent more likely to have colon cancer than individuals without the marker. The researchers estimate that this single genetic variation might account for 14 percent of colorectal cancer cases in Israel, where colon cancer is the leading cause of cancer deaths. The specific marker is called the C allele of rs10505477.

Three other research teams are reporting similar findings today in the journal Nature Genetics, having simultaneously found their way to the same small area of chromosome 8, called 8q24, in the search for colon cancer genetic links. The fact that these studies were performed among other populations around the world suggests that this one genetic marker is highly influential across ethnic groups.

The new Cancer Biology and Therapy paper is by an international group of scientists from the University of Michigan Medical School and U-M School of Public Health, the Catalan Institute of Oncology in Spain, the CHS National Israeli Cancer Control Center and Technion - the Israel Institute of Technology.

Its the product of an ongoing Michigan-Israel collaboration, the Molecular Epidemiology of Colorectal Cancer project, which for 10 years has searched for clues to colon cancers genetic roots using samples from large numbers of people in Israel with known ancestral heritage. The project is funded by the National Cancer Institute, with additional funding from the Irving Weinstein Foundation.

The researchers compared the genetic makeup and family history of more than 1,800 colorectal cancer patients with that of 1,900 healthy people with the same breakdown of age, gender and ethnicity - either Ashkenazi Jew, Sephardic Jew or Arab/non-Jew. Samples of tumor tissue from many cancer patients were also tested. The genetic link between the marker and colon cancer was especially strong among patients diagnosed with colon cancer at a young age, under 50 years.

Stephen Gruber, M.D., Ph.D., the co-leader of the Michigan-Israeli team and first author of the new paper, says that the new finding is particularly interesting when considered alongside recent discoveries in the genetics of prostate and breast cancer.

The same genetic region that predisposes to colon cancer has also recently been shown to be an important region predisposing to breast cancer and prostate cancer, he says. The specific genetic cause for this joint susceptibility to three different cancers has not yet been discovered, but several groups are working to close in on the mechanism that might cause these cancers.

Gruber is an associate professor of internal medicine and of human genetics in the U-M Medical School, and of epidemiology in the U-M School of Public Health. He directs the Cancer Genetics program in the U-M Comprehensive Cancer Center, which focuses on inherited cancer risks.

Genetic discovery in Israel through MECC has already proven highly informative. Senior author Gad Rennert M.D., Ph.D., of the Carmel Medical Center and the B. Rappaport Faculty of Medicine at Technion in Haifa, Israel, says The study of populations in Israel has been shown to be exceptionally fruitful in contributing to knowledge about the genetics of leading cancers. This is due to the unique characteristics of the population and our ability to study it in a representative manner.

Unraveling the mysteries of the susceptibility to disease is moving rapidly since the publication of the complete sequence of the human genome in 2003. Says Gruber, The mystery of the relationship between our genetic code and disease is now starting to become clear, and many scientists are turning to the same chapter to find important clues to colorectal cancer. He and his colleagues plan to continue their effort to zero in on the genetic variations involved in cancer.

While there is not yet a screening test for the genetic variation that was pinpointed in the study, Gruber and his co-authors emphasize that genetic testing is available for other known genetic variations linked to colorectal cancer. People with a strong family history of colon cancer, especially cases that began when relatives were younger than age 50, should get genetic counseling and have colonoscopies or other screening tests starting earlier in life than age 50.

Colon cancer is one of the most common cancers in the United States, and the good news is that its largely preventable with early screening, says Gruber. The American Cancer Society estimates that some 150,000 new cases of colon cancer will be diagnosed in 2007, and more than 50,000 deaths from colorectal cancer will occur.

Although most cancers are not inherited, some families are particularly susceptible to cancer and may benefit from early detection or other risk reduction strategies. People concerned about a family history of cancer, or those who have been diagnosed with colon cancer before age 50 or after having two or more relatives diagnosed with the disease, should talk to their doctor about the possible benefits of genetic counseling, Gruber says. Counseling can be done for both patients and family members.

Why liver cancer is more prevalent in males than in females

Thu, 05 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Production of a protein that promotes inflammation appears to be linked to the higher incidence of liver cancer in men than in women, researchers at the University of California, San Diego (UCSD) School of Medicine have determined in mouse studies. Their discovery that female mice produce far less of the protein called interleukin-6 (IL-6) in response to liver injury than males do, and that production of this protein is suppressed by estrogen, may point the way to therapies to reduce the incidence of liver cancer in males. IL-6 contributes to the chronic liver inflammation that leads to cancer.

The research team was led by Michael Karin, Ph.D., professor of pharmacology in UCSDs Laboratory of Gene Regulation and Signal Transduction. The findings will be published in the July 6 issue of the journal Science.

Males show a higher rate of inflammation than females in the same diseases, including cancer, said Willscott Naugler, M.D., clinical instructor in UCSDs Department of Medicine and first author of the paper. We wondered if increased inflammation was behind the higher incidence of liver cancer in males and, if so, how and why?

Heptocellular carcinoma (HCC) a devastating complication of chronic liver disease and inflammation caused by risk factors such as hepatitis B and C viruses, or alcoholic liver disease makes up the majority of liver cancers in humans. Overall, men are three to five times more likely to develop HCC than women; however, in individuals who are under 50, HCC is seen seven to 10 times more frequently in men. A similar or even more pronounced gender disparty is seen in mice.

In order to understand the mechanisms underlying gender disparity in HCC, the UCSD researchers used a chemical carcinogen, DEN, to induce cancer in mice. This resulted in HCC in 100 percent of male mice, but only in 10 to 20 percent of their female littermates.

The researchers discovered that normal female mice given DEN produced far less IL-6 than the males. Comparing the normal mice to knockout mice missing the IL-6 cytokine, the scientists found that when knockout mice were given DEN, both males and females developed liver cancer at the same, lower, rates.

By eliminating IL-6, we reduced the incidence of liver cancer in the males by close to 90%, Karin said. However, the missing IL-6 made no further difference in female mice.

The researchers then treated normal male mice with estrogen, and exposed them to DEN. The IL-6 level in those males was reduced to the same level as in female mice, as was the degree of liver injury. Experiments on specialized cells in the liver that produce IL-6 showed that estrogen acts on these cells to suppress IL-6 production.

A similar mechanism may account for the gender bias in liver cancer in humans, according to the researchers. Their discovery could lead to development of therapies to reduce development of liver cancer in males by either decreasing the levels IL-6 in males, interfering with IL-6 action or by administering estrogen-like compounds to males in order to inhibit production of IL-6.

While some organs, such as breasts, are clearly influenced by gender, others like the liver are not, said Naugler. So its quite interesting that liver inflammation is so markedly suppressed by estrogens. It raises the possibility that organs not usually associated with gender differences may be governed by the same principle. Bladder cancer, for example, occurs more frequently in males than females, and the differences may be a result of higher IL-6 levels and inflammation in male bladders.

Ablation procedure proves safe, effective and fast

Fri, 29 Jun 2007 17:01:37 PST

( from http://www.rxpgnews.com ) Multiple-electrode radiofrequency ablation is a safe and effective way of treating patients with liver cancer that can be completed in less time than current ablation techniques, according to a recent study conducted by researchers at the University of Wisconsin in Madison.

?One of the biggest limitations of current radiofrequency ablation techniques is the inability to effectively treat large tumors? said Paul Laeseke, PhD, lead author of the study. ?Current radiofrequency ablation systems can only power one electrode and create relatively small ablation zones,? Dr. Laeseke said. Large tumors are treated by sequentially overlapping the small ablation zones--a technique that is both complicated and time consuming,? he said.

The study consisted of 38 malignant liver tumors in 23 patients who underwent multiple-electrode radiofrequency ablation. Local control was achieved in 37 of 38 tumors, with 34 of these tumors treated during just one session. The total ablation time was reduced by approximately 54% compared to if the patients would have been treated using a single-electrode system, Dr. Laeseke said.

?A reduction in procedure time would make staff and imaging equipment available for other cases,? said Dr. Laeseke. ?The treatment success rates in this study are comparable to those reported in the literature for smaller tumors treated with single-electrode radiofrequency,? he said. ?In other words, the multiple-electrode system allowed us to effectively treat larger tumors in less time.?

Dr. Laeseke cautioned though that these are short-term results. ?While the short-term results are promising and demonstrate that multiple-electrode radiofrequency ablation is safe and effective, longer term follow-up is needed to determine the impact of multiple-electrode radiofrequency ablation on patient survival and tumor recurrence rates,? he said.

The full results of this study appear in the June issue of the American Journal of Roentgenology, published by the American Roentgen Ray Society.

Elevated pepsin levels may lead to rejection of lung transplants

Fri, 15 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Researchers in the United Kingdom have demonstrated that high levels of pepsin, a digestive enzyme that is a marker for gastric aspiration, are associated with acute rejection of a lung transplant. This research provides further evidence that lung rejection may be caused by factors other than alloimmunity, the attack the body mounts to protect itself against foreign cells.

We think gastric aspiration [the taking of stomach fluids into the lung] may contribute to an overall injury to the transplanted lung, said Chris Ward, Ph.D., lead author of the study. This pattern of injury may be similar to rejection or increase the risk for further rejection.

Dr. Ward, of Newcastle University, and the other researchers reported their findings in the June 15, 2007, issue of American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

The study included 36 lung transplant recipients, 17 subjects with normal lung function but unexplained cough who served as disease controls for the study, and 4 normal, nonsmoking control subjects. The researchers determined pepsin levels in all the subjects using bronchoalveolar lavage (BAL)

Our primary finding was that, compared with control subjects, wrote the researchers, BAL pepsin levels were elevated in stable lung transplant recipients, subjects with acute rejection, and subjects with bronciolitis obliterans [a common manifestation of lung transplant rejecton]. Our secondary finding was that the highest levels of pepsin appeared in the transplant recipients with clinically significant acute rejection (grade A2 or greater).

These findings support the growing recognition that gastroesophageal reflux (GER) is a potential cause for post-transplant lung injury and other airway and lung diseases. Although none of the transplant patients were formally evaluated for GER, nearly all were treated with acid suppression medications, which is standard therapy after lung transplantation.

Despite those medications, known as proton pump inhibitors, the researchers found evidence of gastric aspiration. It is important to recognize that proton pump inhibitors do not prevent reflux per se, but rather act to cut down on acidic reflux, the researchers noted. They also noted, that in addition to the damage that might be done to the new lung by acid reflux, pepsin is not targeted by these drugs and may be a separate cause of lung injury.

The researchers reported that the disease control groupthose with normal lung function, but unexplained coughdid not have pepsin in their lungs, even when 10 of 17 were diagnosed during the study as having gastroesophageal reflux disease (GERD). A diagnosis of GERD does not mean that patients are refluxing out of the esophagus and hence aspirating, they explained. Even if the refluxate reaches the upper airway, it is almost certainly cleared by a hyperactive cough reflex.

In their article, the researchers note ongoing studies being done at Duke University that appear to show lung transplant patients who undergo fundoplication, a surgical procedure that strengthens the valve between the stomach and the esophagus, before the transplant have longer survival rates and delayed onset of bronchiolitis obliterans syndrome than those who do not.

If fundoplication is confirmed as a useful prophylaxis in preventing lung rejection, they write, markers of aspiration may contribute to identifying patients who might derive clinical benefit.

Identification of genetic risk factor for coeliac disease promises improved treatment

Sun, 10 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) An international research consortium investigating the genetic causes of intestinal inflammatory conditions has identified a new genetic risk factor for coeliac disease. The findings, published online today (10 June 2007) in the science journal Nature Genetics, could pave the way towards improved diagnostics and treatments for the common, lifelong complaint.

Led by David van Heel, Professor of Gastrointestinal Genetics at Queen Mary, University of London, the study - funded by the charity Coeliac UK, and the Wellcome Trust - has revealed that those suffering from coeliac disease lack a protective DNA sequence in a specific gene region, otherwise found in healthy individuals.

Behind the success of the study are the Human Genome Project and the Hap Map Project, international research efforts to reveal the entire sequence of all the human chromosomes - and the functional units embedded within - and to correlate that information to common sequence variation in the human population.

Dr Panos Deloukas, Senior Investigator in Human Genetics at the Wellcome Trust Sanger Institute, and part of the research consortium, said: These resources coupled with technological advances have enabled us to scan variation across the human genome in large numbers of people for association to disease. The Sanger Institute made available to the study the genome data on 1500 British individuals used as controls (i.e without coeliac disease). The consortium studied over four thousand individuals with and without coeliac disease, amongst British, Irish and Dutch populations.

What they found is that healthy individuals more often have a protective DNA sequence in the interleukin-2 and interleukin-21 gene region than individuals with coeliac disease. Interleukin-2 and interleukin-21 are cytokine proteins secreted by white blood cells that control inflammation. It is likely that the protective DNA sequence leads to different amounts of these cytokines being produced than in someone with coeliac disease providing defence against intestinal inflammation.

Coeliac disease is found in around 1 in 100 of the British population. It is caused by intolerance to gluten - a protein found in wheat, barley and rye - which results in damage to the gut, preventing normal digestion and absorption of food. If undetected it can lead to, amongst other things, anaemia, poor bone health, and weight loss. Although the majority of people are diagnosed in mid-life, symptoms can present themselves at anytime, for example during illness, stress, or post-trauma. There is a strong inherited (genetic) risk.

Professor David van Heel, chief investigator in the study, said; We previously knew that coeliac individuals had a specific tissue type which recognised wheat proteins. We did not know why healthy individuals who had the same tissue type did not develop symptoms or disease. The first findings from our study suggest that interleukin genes that control inflammation are critical. We expect to find more disease risk factors from further in-depth analysis of the genome wide data.

Sarah Sleet, Chief Executive of Coeliac UK said: This research heralds an important breakthrough in understanding better who is likely to develop coeliac disease. Around 1 in 100 people develop the disease but predicting who is susceptible is like searching for a needle in a haystack. Currently genetic testing is a blunt instrument which can only narrow down the search to around one third of the general population.

The study provides a road-map to enable discovery of further genetic risk factors predisposing to coeliac disease.

PET/CT should be 'first-step' test for patients with Crohn's disease

Mon, 04 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) WASHINGTON, D.C.The molecular imaging power of PET/CT is invaluable in noninvasively monitoring Crohn's diseasea chronic inflammatory disease of the gastrointestinal tract that mainly affects young people, according to a study released by Belgian scientists at the 54th Annual Meeting of SNM, the world's largest society for molecular imaging and nuclear medicine professionals.

Our study is the first one demonstrating the value of PET/CT in Crohn's disease, said Roland Hustinx, head of the nuclear medicine division at the University Hospital of Liège and professor of nuclear medicine at the University of Liège. PET/CT (positron emission tomography/computed tomography) imagingwith the radiotracer fluorodeoxyglucose or FDGcould be used as a first-step test in patients with clinical or biological signs suggesting active disease, he noted. PET/CT can answer the major question: What is the activity of the disease explained Hustinx.

Crohn's disease, an inflammatory bowel disease (IBD) that can affect the digestive system, has no medical cure, and its causes are unknown, explained Hustinx. Once the disease begins, it can fluctuate between periods of inactivity (remission) and activity (relapse). During relapses, symptomsvarying in nature, frequency and intensityinclude abdominal pain, diarrhea and worsening general physical condition. Estimates indicate that up to 2 million people in this country could be affected by Crohn's and related diseases. IBD most commonly begins during adolescence and early adulthood.

The clinical course of the disease is characterized by a succession of periods of clinical relapses and remissions, said Hustinx. Its diagnosis relies on clinical and biological signs (markers of inflammation in the blood) as well as direct examination of the bowel using ileocolonoscopy, an endoscopic examination of the large bowel, where the last part of the small bowel (ileum) is also examined, added Hustinx, who indicated that prevalence of the disease is increasing.

Endoscopic evaluationa diagnostic medical procedure in which a small, flexible tube with a light and lens is inserted into the body to assess the interior surfaces of an organis the gold standard to answer, 'What is the activity of this disease' said Hustinx. The answer to this question will decide whether the clinician prescribes a treatment that is likely to be effective but also very costly and associated with side effects. Ileocolonoscopy is invasive, unpleasant for the patient, sometimes incomplete due to unreachable segments and can only assess mucosal lesions, while the disease may sometimes affect deeper parts of the bowel wall, he indicated.

The big advantage of PET/CT is that it is noninvasive, simple, fast and without any side effects. There was no preparation for the patients, except that they fasted for six hours. Each study took less than 20 minutes, said Hustinx. If the PET/CT is positive, the doctor should confirm the results using endoscopy. If the PET/CT is negative, there would be no need for the endoscopygiven the high negative predictive value of the technique, he added.

In our study, all bowel areas that showed severe endoscopic lesions were correctly identified by PET/CT. There was not a single case in which the ileocolonoscopy showed severe lesions and PET/CT showed a normal metabolic activity, said Hustinx. Conversely, this means that when the PET/CT is negativeno matter how important the clinical symptoms arethe disease is not active, he added. PET/CT has, therefore, the potential to deeply modify the exploration algorithm of patients with Crohn's, reducing the number of endoscopic examinations and allowing a better, noninvasive monitoring of the disease's activity, he indicated.

PET/CT molecular imagingwith radioactive drugs such as FDGenables the collection of both biological and anatomical information during a single exam, with PET picking up metabolic signals of body cells and tissues and CT offering a detailed map of internal anatomy.

Our results must be confirmed by other investigators on a larger scale, said Hustinx, indicating that his team is currently conducting a study evaluating the capacity of PET/CT to assess early on the response of the disease to biological treatments. Treatment has been significantly improved over the past few years with the development of biological treatments, which have shown potential for obtaining mucosal healing in Crohn's disease, noted Hustinx. This mucosal healing has been associated with higher sustained quality of life, lower rate of hospitalization and lower need for surgery. A sustained clinical remissionand a control of intestinal lesionhas become the target of new treatment strategies, he said.

Molecular motors may speed nutrient processing

Wed, 30 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Matthew Tyska, Ph.D., recalls being intrigued, from the first day of his postdoctoral fellowship in 1999, with a nearly 30-year-old photograph. It was an electron micrograph that showed the internal structures of an intestinal cell microvillus, a finger-like protrusion on the cell surface. Microvilli are common features on the epithelial cells that line the bodys cavities.

At the time, Tyska knew that the core bundle traveling up the center of the microvillus was an array of the structural protein actin, and that the ladder-like rungs connecting the actin bundle to the cell membrane were composed of the motor protein myosin-1a. This myosin, though related to the myosin involved in muscle cell contraction, was thought to serve a purely structural role.The textbook thinking for decades was that microvilli serve as a passive scaffold, a way to amplify the membrane surface area, said Tyska, assistant professor of Cell and Developmental Biology at Vanderbilt University.

In the intestines, an expanded cell surface increases the space for nutrient-processing enzymes and transporters, offering greater capacity for nutrient handling.But it didn't make sense to Tyska that a motor protein a protein with the potential to generate force and move cargo around in cells would play a passive structural role.When I looked at that image, the near crystalline arrangement reminded me of actin and myosin in a muscle fiber, Tyska said. I kept returning to the same question: why would the microvillus have this beautiful structure packed with motor proteins. The concentration of myosin motors in a single microvillus is very high; theres serious force-generating potential there.

Tyska and Russell McConnell, a student in his laboratory, tested the idea that these motor proteins are more than molecular glue binding the cell membrane to the actin bundleThe investigators purified the intestinal brush border the layer of densely packed microvilli from the intestines of rats or mice, and added ATP, the chemical fuel for myosin-1a. Through the microscope, they watched the cell membrane move toward the tips of the microvilli and pop off the ends in the form of vesicles, tiny bubble-like packets.

Their findings, reported in the May 21 Journal of Cell Biology with one of their images featured on the issue cover, have implications for nutrient processing and other aspects of gastrointestinal physiology.Tyska is excited about the groups unexpected discovery.What were showing is that the microvillus is more than just a scaffold to increase the amount of cell membrane, Tyska said. Its a little machine that can shed membrane from the tips.The team confirmed that myosin-1a is the motor that moves membrane up the microvillus. Brush borders isolated from knockout mice lacking the myosin-1a gene shed membrane at only five percent of the level of brush borders from wild-type animals.

The investigators are working now to understand why intestinal cells might launch vesicles from their microvilli. They know from ongoing vesicle sorting and mass spectrometry studies that the vesicles contain nutrient-processing enzymes and transporters, like the microvillar membrane.One idea is that these vesicles operate remotely to speed nutrient processing, before the nutrients even get to the brush border to be absorbed by the (intestinal epithelial cell), Tyska said.

The team is also exploring other possibilities for the role of membrane shedding: that it offers protection against microbes and pathogens by expelling them from the surface before they can enter the cell; that it provides a mechanism for altering the composition of the microvillar surface to handle changes in what comes down the pipe; and that it serves a role in cell-cell communication by launching vesicles that contain signaling proteins. Tyska and his team also plan to explore whether myosin-1a is serving a similar membrane-moving role in its other known location: the hair cells of the inner ear, and if other microvilli also use myosin motors to jettison vesicles from their tips.

Doctors, engineers develop new wireless system to detect esophageal reflux

Tue, 29 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) DALLAS May 29, 2007 -- UT Southwestern Medical Center doctors and UT Arlington engineers have developed a wireless monitoring system that uses electrical impulses to track esophageal reflux.

The wireless technology, called radio frequency identification (RFID), has been used in thousands of stores for tracking inventory and in identification chips implanted in some pets. Researchers combined that technology with another emerging applied science called impedance monitoring, which tracks reflux through electrical impulses.

We always want to come up with something that improves what we do on a daily basis, said Dr. Shou Jiang Tang, assistant professor of internal medicine at UT Southwestern who specializes in therapeutic endoscopic and endoscopic innovations.

According to the American College of Gastroenterology, approximately 19 million people have gastroesophageal reflux disease (GERD), which is caused by stomach content moving upward from the stomach into the esophagus.

The new system involves pinning a small, flexible RFID chip to the esophagus, where it remains until removed by a physician. The chip, about two square centimeters, or a little bigger than a dime, tests for electrical impulses that signal acidic or nonacidic liquids moving through the esophagus. It then transmits data to a wireless sensor worn around the neck.

The device, presented May 23 at the Digestive Disease Week conference in Washington D.C., is still in the test phase. But researchers believe it will be a welcome replacement for current standard procedures, which require placing a flexible catheter tube through the nose and down into the esophagus.

The procedure is very uncomfortable and because of the catheter, you cant eat or drink the way you normally would. The test results can be biased because you change the way you eat, explained Dr. Tang.

No catheter is required with the RFID system, so doctors are hopeful that the system makes it easier to follow normal eating, drinking and activity patterns that may play a part in the acid reflux. Researchers say patients shouldnt feel anything in their throat when the device is inserted thanks to a special plastic material used.

The RFID system is the next step in a growing effort to develop less invasive wireless technologies for gastrointestinal diseases. Those include the PillCam, a small pill-sized wireless camera that takes photos as it goes through the digestive tract, and Bravo capsule, another wireless system that detects esophageal acids. Both technologies are currently used by UT Southwestern gastroenterologists.

Researchers have already successfully tested the new RFID device to see that it properly identifies simulated stomach acids in a test tube and that the transmitter can send the results through human tissue. The sensor is designed to detect stomach acid, gas and water so doctors can determine whether the presence of those substances coincides with feelings of heartburn, the start of eating or other activities. The next step will involve testing in animal models before the system eventually is tested in humans.

UT Southwesterns Dr. Tang and Dr. Fred Tibbals, director of the Bioinstrumentation Resources Center, have been working with Dr. Jung-chih Chiao, associate professor of electrical engineering at UTA, for two years to develop the wireless system. Engineers had to develop the specialized radio frequency implant, which detects and sends the data, as well as the receiver. The receiver will include a button the patient can push when they begin eating. Eventually, engineers hope to design a devise similar to a personal digital assistant to store the results. That PDA-like device could then be taken into a doctors office and downloaded into a computer to analyze the results.

New technique effective in closing accidental colonoscopy wounds

Wed, 23 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) WASHINGTON, D.C. -- To prevent colon cancer, the second leading cause of United States cancer deaths, the American Cancer Society recommends that after age 50 people undergo colonoscopies every ten years to detect signs of that disease either actual tumors or precancerous polyps.

But in one out of every 1,000 to 2,000 colonoscopies, doctors inadvertently perforate or puncture the colon. Most of these patients need urgent surgery to close the wound and spend 10 days in the hospital. One in 10 dies, usually because delays in closing perforations allow colon contents to leak into the abdominal cavity, causing deadly conditions such as peritonitis and sepsis.

Now, however, in a series of animal studies, researchers at the University of Texas Medical Branch at Galveston (UTMB) have developed a technique for closing perforations promptly after they are recognized by using clips or sutures that can be inserted through the anus via endoscope, thus avoiding invasive surgery. Similar clips and sutures have been used for some time by surgeons performing minimally invasive laparoscopic procedures including several gynecological operations and other procedures such as gall bladder removal.

Today [Wednesday, May 23, 2007] at the annual meeting of the American Society of Gastrointestinal Endoscopy, UTMB professor G.S. Raju, the principal investigator for the wound-repair studies, presented a summary of his experimental endoscopic research over the last three years.

Working with pigs as an experimental model, Raju and his team first successfully closed colon perforations of less than one inch with small metal clips inserted via endoscopes.

During colonoscopies, surgeons accidentally may cause two principal types of perforations, Raju explained. One results from over-stretching the colon, the other from removal of polyps. (Incomplete removal of polyps may cause adhesions, in which the remaining portion of the polyp sticks to the colon wall.) We have shown in a series of experiments that both types of perforations can be closed successfully using an endoscope without the need for invasive surgery, Raju reported. He added: We have even accomplished a leak-proof seal of the perforation.

Encouraged by the preliminary work done at UTMB, InScope, a branch of Ethicon Endosurgical of Cincinnati, invited Raju to initiate and lead a multi-center animal study comparing surgical closure with endoscopic efforts to close a gaping, 1.6-inch-wide colon perforation using new clips and sutures. Other institutions joining in the multi-center trial included academic medical centers at Dartmouth University and the University of Cincinnati, and at medical schools in Great Britain and Sweden. The results are encouraging, Raju said: As good as surgery in closing perforations, better than surgery in reducing adhesions.

Experience gained from laboratory experiments was quickly used to improve patient care at UTMB, Raju noted. Recently, two patients who were not good candidates for surgery were successfully treated at UTMB for postoperative leaks following esophageal and colon cancer surgery using the clip technology.

Raju said he expects that by next year, experience gained in the laboratory will allow his UTMB surgical colleagues Drs. Guillermo Gomez and William Nealon to help patients with gastrointestinal perforations and postoperative leaks. In addition, he said those surgeons hope to explore the role of endoscopy in treating patients with gastrointestinal tumors. He predicts that the minimally invasive endoscopic procedures will help such patients experience less pain, faster healing, less hospital time and lower medical costs, as is the case with laparoscopic procedures.

As for colon wound repair, Raju said if human clinical trials are as successful as those done in pigs, he would expect these procedures to be commonly adopted in hospitals in the near future.

Raju said the UTMB Center for Endoscopic Research, Training and Innovation, (CERTAIN), which he directs, plans to develop courses to train physician colleagues in the region in how to use clips and sutures to close perforations.

Could statins be a new option for hepatitis C patients?

Tue, 22 May 2007 09:59:37 PST

( from http://www.rxpgnews.com ) WASHINGTON, D.C. (May 20, 2007) -- Research presented today at Digestive Disease Week? 2007 (DDW?) demonstrates the potential of statins, important cholesterol management therapies, for improving the management of hepatitis C ? a disease that affects nearly four million Americans. Although there have been no new treatments for hepatitis C since the introduction of pegylated interferon in 2001, the opportunity to develop a new generation of therapies that offer better outcomes may be imminent. DDW is the largest international gathering of physicians and researchers in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.

Studies such as these are designed to improve the effectiveness of antivirals ? the standard of care therapy for hepatitis C, said John Vierling, M.D., Baylor College of Medicine. The findings from these studies support the rationale and need for larger, controlled trials that may provide additional and more advantageous hepatitis C treatment options.

New Mayo Clinic MRI technology enables noninvasive liver diagnoses

Tue, 22 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) ROCHESTER, Minn. -- Two recent Mayo Clinic studies have found that magnetic resonance elastography (MRE), a new imaging technique invented at Mayo Clinic, is an accurate tool for non-invasive diagnosis of liver diseases. The findings will be presented this week at the International Society for Magnetic Resonance in Medicine Annual Meeting in Berlin, Germany, and Digestive Disease Week 2007 in Washington, D.C.

The liver responds to many diseases that damage its cells by developing scar tissue or fibrosis. MRE uses a modified form of magnetic resonance imaging (MRI) to accurately measure the hardness or elasticity of the liver. By applying vibrations to the liver, MRE obtains pictures of the mechanical waves passing through the organ. The wave pictures are then processed to generate a quantitative image of tissue stiffness.

Healthy liver tissue is very soft, while a liver with fibrosis is firmer, and a liver with cirrhosis is almost rock-hard, says Richard Ehman, M.D., lead researcher on the MRE project. If detected early, fibrosis of the liver can be treated, but once the disease has progressed to cirrhosis, the condition is irreversible.

Dr. Ehman and his imaging research team collaborated with Mayo Clinic gastroenterologists to study whether MRE could provide reliable and accurate diagnoses in patients with varying degrees of liver disease.

One study involved MRE examinations of 57 individuals with chronic liver disease and 20 healthy volunteers. The researchers confirmed that MRE accurately detects fibrosis with high sensitivity and specificity. Researchers also found that steatosis, which is deposits of fatty acids and triglycerides in liver cells and a common condition in patients with liver disease, did not interfere with detection of fibrosis with MRE.

Based on this research, we are now using MRE examinations in select patients to determine liver stiffness and assess the need for liver biopsies, says Jayant Talwalkar, M.D., a Mayo Clinic gastroenterologist and an investigator on the MRE studies. More than 170 million people in the world are known to have hepatitis C, and nearly one-fourth of those will develop severe liver fibrosis. MRE can help us noninvasively identify fibrosis in this large patient population.

A second study looked at whether MRE can accurately measure portal hypertension, or high blood pressure in the portal vein that carries blood from the digestive track to the liver, usually as a result of cirrhosis of the liver. This study involved 35 individuals with varying degrees of chronic liver disease and 12 healthy volunteers. Researchers studied MRE examinations of liver and spleen stiffness and found that a highly significant correlation exists between liver and spleen stiffness in patients with portal hypertension. However, the validity of spleen stiffness as a noninvasive measure of portal venous pressure requires further study.

According to Dr. Ehman, many diseases cause the properties of tissue to change and will be likely candidates for diagnosis using MRE in the future. His research team is exploring the use of MRE in detecting breast cancer and Alzheimers disease.

New approach to treating precancerous esophagus condition

Tue, 22 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) DURHAM, N.C. The use of concentrated radio waves appears to be a safe and effective way to burn away abnormal cell growth in the esophagus that can be a precursor of cancer.

The new procedure is being tested in patients with Barrett's esophagus, a condition associated with the continued reflux of stomach acids into the lower esophagus that can damage its lining over time. While this condition is relatively common, a small percentage of patients will go on to develop abnormal cell growth known as dysplasia, a condition that can lead to esophageal cancer.

Gastroenterologists at Duke University Medical Center found that delivering concentrated radio waves through a catheter inserted down the esophagus can effectively treat the dysplasia with fewer side effects than current treatment methods. After the treatment, known as radiofrequency ablation, the treated cells die, slough off and are replaced within four to six weeks by new, healthier cells.

In a review of the first 12 patients treated with radiofrequency ablation at Duke, gastroenterologist Darren Pavey, M.B.B.S., found that three months after treatment, 89 percent of patients had more normal-looking esophageal tissue when viewed with an endoscope inserted down the esophagus. When samples of the new cells were analyzed in the laboratory, half of the patients were shown to have healthier tissues.

Pavey presented the results of the analysis on Tuesday, May 22, at the annual Digestive Disease Week conference in Washington, D.C. His analysis was supported by Duke's Division of Gastroenterology.

In the procedure, which takes about 20 to 30 minutes, we insert a catheter down the esophagus and superficially burn the layer of cells that are abnormal, Pavey said. The procedure is performed on patients as an outpatient procedure under conscious sedation, much as during a colonoscopy. The patients find that they have little or no discomfort following the procedure.

Pavey said that if radiofrequency ablation is proven effective in larger trials now under way, physicians will be able to offer a technique that has fewer side effects and is better tolerated by patients.

There are currently two main treatments for Barrett's esophagus with high grade dysplasia. The surgical approach involves removing the affected portion of esophagus. It is a major operation that has up to a 6 percent mortality rate and also can leave patients with reflux and swallowing problems, Pavey said.

A second approach, in use for the past 10 years, is known as photodynamic therapy. It involves a photosensitizing agent that is preferentially taken up by abnormal cells. Physicians then shine a laser light into the esophagus, and the light kills the target cells. However, patients must avoid direct sunlight for several weeks, and up to 30 percent of patients experience scarring of the esophagus severe enough to affect swallowing.

So far, radiofrequency ablation seems to be less invasive than surgery and better tolerated than photodynamic therapy, Pavey said. This approach has the potential to dramatically alter the way we treat patients with Barrett's esophagus.

While the incidence of Barrett's esophagus is difficult to determine, studies at autopsy indicate that the condition occurs in one in every 60 to 80 people in the United States, mostly in Caucasians. It also occurs four times more frequently in men than women. About 10 percent of patients with long-term gastrointestinal reflux, or heartburn, will go on to develop Barrett's esophagus.

In our study, we also found that radiofrequency ablation appears to be effective for those patients who have had an incomplete response following treatment with photodynamic therapy, Pavey said

New prevention, treatment methods for patients with painful bowel inflammation

Mon, 21 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Inflammatory bowel disease, or IBD, is an umbrella term referring to a group of disorders that cause inflammation of the intestines, including ulcerative colitis, diverticular disease and perianal fistula.

Nearly one million Americans experience some form of IBD every year, which is often chronic or recurring. Research presented today at Digestive Disease Week? 2007 (DDW?) looks at preventative measures and potential treatment options for these painful and debilitating conditions. DDW is the largest international gathering of physicians and researchers in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.

Inflammatory bowel diseases are serious and complex diseases with varied preventative and treatment options, and we are pleased to see more attention directed toward improving the lives of people suffering from these conditions, said Marí¡ Abreu, M.D., Director, Inflammatory Bowel Disease Center, Associate Professor of Medicine, Mount Sinai School of Medicine. The studies presented today provide evidence that scientists are beginning to capitalize on previous research to better understand, prevent and treat intestinal inflammation.

Mice, men make livers differently

Mon, 21 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) CAMBRIDGE, Mass. -- Scientists often study mice as a model for human biology and disease, because their basic biological processes are assumed to be essentially the same as those of humans.

But now, a team of MIT researchers has uncovered a surprising difference. In a study of gene regulation in mouse and human liver cells, they found that master regulatory proteins function in very different ways in mice and humans.

Evolution has discovered several different ways to make a liver from the same building blocks, said Ernest Fraenkel, MIT assistant professor of biological engineering and leader of the research team. Comparing these different ways of regulating genes may unlock some of nature's most closely guarded secrets.

The work, which will be published in the May 21 online edition of Nature Genetics, could help identify patterns in the extremely complicated control mechanisms involved in gene expression.

You can think of it as two different dialects of the same language. By exploring the human and mouse versions, we hope to find an underlying grammar, said Fraenkel.

Every cell in the human (or mouse) body has the same collection of genes, but the genome of each cell is carefully regulated so that only certain genes are expressed. Regulatory proteins known as transcription factors control this expression by binding to specific locations within the genome and turning nearby genes on or off.

The researchers and their colleagues had previously worked out many aspects of gene regulation in the human liver, which is one reason the researchers chose to study the liver. In the current study they compared 4,000 human genes with nearly identical counterparts, known as homologous genes, from mouse liver cells.

Given the similarity between the two species DNA sequences, the researchers expected that transcription factors would bind to the same sites in most pairs of homologous genes. To their surprise, they found that most of the binding sitesbetween 41 percent and 89 percent, depending on the transcription factorwere in different locations in humans and mice.

The number of genes with the identical regulation in both species was very, very small, Fraenkel said.

Before they began, the researchers expected to see some differences in gene regulation between mice and humans, because the human liver has evolved to process cooked food, said Fraenkel. However, the magnitude of change was much higher than they anticipated.

Fraenkel speculated that the changes accumulated without having much of an effect on gene expression. Unless the location of binding sites affects gene expression, it is not under any natural selection pressure.

All of that meaningless variation makes it harder to identify the small number of genes where binding site migrations do have an evolutionary impact, because they are being drowned out by all the insignificant changes, Fraenkel said. In future studies, the research team plans to investigate why some genes binding sites are conserved over time while others shift.

We want to understand whats special about those genes, Fraenkel said.

Fraenkel said the results should provide guidance for researchers who study mice to better understand human biology. To get the most out of mice for biomedical research we need to fully map out the regulation in both organisms, he said.