Scientists have uncovered vital clues about how to treat serious bowel disorders by studying the behaviour of cells in the colon.

Researchers at the University of Edinburgh believe a chemical messenger that is essential for developing a baby’s gut in the womb could hold the key to new treatments for inflammatory bowel disease (IBD), a condition which affects 1 in 250 people in the UK.

The team studied a chain of chemical reactions inside colon cells, called the Hedgehog signalling pathway, which controls the way it behaves and communicates with other cells.

The researchers found that some patients with IBD inherit a defective copy of one of the important links in this chain, a gene called GLI1. This defective GLI1 is only half as active as normal. Additionally, the Hedgehog pathway itself signals at lower levels than normal when the large bowel is inflamed.

The results suggest that the GLI1 protein may calm inflammation within the healthy colon, and that this process appears to go wrong in IBD patients, causing their gut to become inflamed.

The researchers now hope to test whether strengthening this weakened protein will help to prevent or treat inflammatory bowel diseases like Crohn’s disease and ulcerative colitis.

Dr Charlie Lees from the University’s Institute of Genetics and Molecular Medicine, who led the study, said: “Everybody has billions of bacteria in the gut, the vast majority of which do us no harm. Our body’s natural immune responses identify and eliminate harmful bacteria, whilst living in harmony with the healthy bacteria. But in people with inflammatory bowel disease, that response goes wrong and an over-active immune response against these healthy bacteria leads to chronic inflammation in the gut.

“It now seems that the Hedgehog signalling pathway, and specifically the GLI1 protein, is crucial to that response. We think it provides an important signal to certain types of immune cells in the gut wall, instructing them to adopt an anti-inflammatory state. If we can find ways to bolster these responses in people with IBD, we may be able to help prevent the painful attacks which are so devastating to patients.”

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An estimated 600 uninsured or underinsured Connecticut residents will be screened for colorectal cancer over the next year as part of a pilot program in which the University of Connecticut Health Center is a primary partner.

“The colonoscopy is a major prevention tool, but not everyone has access,” says Dr. Joseph C. Anderson, clinical director of the UConn Health Center’s Colon Cancer Prevention Program. “The more people we can screen, the more people we can help. Polyps in the colon will become cancerous whether you have insurance or not. People who can’t afford a colonoscopy also can’t afford to not get screened.”

Anderson, who was lead endoscopist in a Centers for Disease Control and Prevention-funded program in 2005 while at Stony Brook University Medical Center in Long Island, and who was a key adviser to a similar undertaking by the South Carolina Gastroenterological Association, is serving as medical director of the Connecticut Colorectal Cancer Screening Demonstration Project and is among the physicians providing the colonoscopies.

Eight community health centers throughout the state will refer eligible patients to participating endoscopists depending on their location. Patient data will be collected and appropriate follow-up referrals will be provided.

“The goal is to promote, improve and optimize the appropriate use of high-quality colorectal cancer screening and follow-up services, and eliminate or decrease racial, ethnic and socioeconomic disparities in access to these screenings,” says Jennifer Granger, chief operating officer of the Community Health Center Association of Connecticut, which received a $951,379 grant from the Connecticut Department of Public Health for the project.

State funding for the grant was available through the Connecticut Cancer Partnership, a coalition working toward the goals of reducing the burden of cancer and improving the quality of life of those with cancer. In addition to providing colonoscopies, the pilot project aims to educate the public and provide outreach and training to the participating community health centers.

“When you break down barriers to preventative medicine, the result is a healthier public,” says Public Health Commissioner Dr. J. Robert Galvin. “We are pleased to partner with community health centers and the University of Connecticut Health Center on this important initiative, which will surely result in saved lives.”

The UConn Health Center will receive up to $353,206, which will cover the costs of reimbursement for cancer screenings, Anderson’s medical directorship and program quality oversight, training and education, and data collection and analysis.

“Dr. Anderson has led the effort to bring this crucial program to Connecticut,” says Dr. Carolyn D. Runowicz, director of the Health Center’s Carole and Ray Neag Comprehensive Cancer Center. “He is a top expert in colon cancer prevention, and prevention is what this is all about. We could almost eradicate colon cancer if only more people were screened.”

The community health center partners are Community Health Services in Hartford, StayWell Health Center in Waterbury, Fair Haven Community Health Center in New Haven, Hill Health Center in New Haven, Southwest Community Health Center in Bridgeport, Optimus Health Care in Stamford, Generations Family Health Center in Willimantic, and the Community Health and Wellness Center of Torrington. The other participating endoscopists are in New Haven, Bridgeport, Stamford, Willimantic and Torrington.

The Community Health Center Association of Connecticut is a not-for-profit service organization dedicated to strengthening and supporting the clinical and administrative operations of its member community health centers. Its mission is to enable federally qualified health centers to provide Connecticut’s underserved citizens access to the highest quality health care and social services. More information about the Connecticut Colorectal Cancer Screening Demonstration Program is available here.

The University of Connecticut Health Center includes the schools of medicine and dental medicine, the UConn Medical Group, University Dentists, and John Dempsey Hospital. Founded in 1961, the Health Center pursues a mission of providing outstanding health care education in an environment of exemplary patient care, research and public service. To learn more about the UConn Health Center, visit our website at www.uchc.edu.

State of Connecticut
http://www.ct.gov

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Use of the drug interferon as a long-term maintenance strategy to slow the progression of liver disease associated with the hepatitis C virus is ineffective, UT Southwestern Medical Center researchers and their colleagues from nine other institutions have found in a multicenter study.

Results of the 3½-year study, called the HALT-C (Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis) Trial, appear in today’s issue of The New England Journal of Medicine. The researchers found no difference in the rate of progression of liver disease among patients who received interferon and those who did not.

“It wasn’t that there was an insignificant difference; there was absolutely no difference whatsoever in the progression to cirrhosis and other disease complications,” said Dr. William M. Lee, professor of internal medicine at UT Southwestern and a principal investigator for the study. “It is a negative study but an important one.”

Dr. Lee said physicians should not expect any benefit from the long-term use of interferon by itself in slowing disease progression. By contrast, use of interferon with other drugs such as ribavirin can lead to viral eradication, or complete clearance of hepatitis C virus, a result that will “stop the disease in its tracks,” Dr. Lee said.

Hepatitis C is a viral infection that causes liver inflammation and can progress over many years to cirrhosis, liver cancer, liver failure and death. The disease affects more than 3 million people in the United States and 170 million people worldwide. It is the most common reason for liver transplantation in the U.S.

There is no vaccine to prevent hepatitis C virus infection. The combination of interferon and ribavirin works for about 40 percent to 50 percent of people with the virus, while the other 50 percent to 60 percent of patients will continue to progress to later states of liver disease, Dr. Lee said.

In addition to interferon and ribavirin, new drug agents such as protease and polymerase inhibitors are being used in clinical studies at UT Southwestern to improve rates of virus eradication. Food and Drug Administration approval of these agents is likely to be three years away, Dr. Lee said.

In the HALT-C Trial, conducted between August 2000 and June 2007, 1,050 people with hepatitis C who did not respond to initial antiviral treatment were assigned randomly to either a group that received treatment with a type of interferon called peginterferon or to a group that did not. About 120 patients were enrolled at UT Southwestern.

Participants were monitored every three months and underwent liver scans and biopsies at specified intervals through the study period. Researchers found that although the level of hepatitis C virus in blood and certain enzymes in the liver decreased significantly with treatment, there was not a significant difference in ultimate clinical outcome.

“Currently, we use interferon only to clear the virus,” said Dr. Lee. “If you cannot clear the virus with treatment, the idea that struggling long term through the side effects of interferon is somehow going to help you rid yourself of cirrhosis is just not plausible any longer.”

Some patients cannot tolerate the side effects of the different types of interferon medication, which can cause extreme flu-like symptoms, such as fever, chills, fatigue, depression, muscle aches, chest pain, difficulty breathing, nausea, vomiting, and weight and hair loss.

Other researchers from UT Southwestern involved in the study were Dr. Thomas Rogers, professor of pathology, and Dr. Peter Malet, professor of internal medicine.

Also involved in the study were researchers from Saint Louis University School of Medicine; Virginia Commonwealth University Medical Center; University of Colorado School of Medicine; University of Southern California; National Institute of Diabetes and Digestive and Kidney Diseases; University of Michigan Medical Center; University of Connecticut Health Center; University of California, Irvine, and VA Long Beach Healthcare System; and University of Washington.

The study was funded by the National Institutes of Health. Pharmaceutical manufacturer Hoffman-LaRoche, through an agreement with the NIH, also provided funding.

Dr. Lee has received consulting fees from Eli Lilly, Fibrogen and Astra Zeneca, and grant support from Hoffmann-LaRoche, Schering-Plough, Vertex Pharmaceuticals, GlaxoSmithKline, Siemens, Globelmmune and Bristol-Myers Squibb.

Visit http://www.utsouthwestern.org/digestive to learn more about UT Southwestern’s clinical services in digestive disorders, including liver diseases.

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North Cheshire Hospitals NHS Trust is asking visitors to the hospitals to consider whether they are well enough to visit sick patients this winter in a bid to reduce the risk of the spread of common bugs including Norovirus.

Each year up to one million people across the country are affected by Norovirus (sometimes called “winter vomiting virus”). It is the most common cause of infectious gastroenteritis in England and Wales and can affect people of any age. It is very contagious as it is spread from person-to-person and through food and water. It can spread quickly in a hospital environment if bought in by unsuspecting visitors.

Whilst Norovirus is an unpleasant experience, the infection tends to only last between 12 and 60 hours and most healthy people will just need to drink plenty of fluids and rest up. However, the illness can have a worse effect on patients in hospital by making them weak and dehydrated and interfering with the effectiveness of the medicines they are taking.

Many hospitals and GP practices around the country have reported a major rise in cases in the last few weeks. So far, Warrington and Halton Hospitals have seen a number of cases which led to them restricting visiting to some wards at times last week. They are asking visitors to be vigilant if they have not been well and have relatives in hospital.

Staff are asking visitors to the hospital to follow three simple steps in a bid to reduce the risk of spreading the bug among patients:

1. Do not visit hospital if you feel unwell. If you, your family or close work colleagues have experienced vomiting and diarrhoea in the last 72 hours please contact the ward for advice before visiting. If you have an outpatient appointment but are unwell, ring and tell us and we can rearrange it for you.

2. Always wash your hands with soap & hot water and/or use hygiene hand rub when entering and leaving the ward.

3. Do not sit on the patient’s bed. If you intend to visit your friend or relative please do not sit on their bed or the patient’s chair. Visitors’ chairs are provided - please ask the nurse if you need more.

“In Winter, stomach bugs like Norovirus are very difficult to control because they spread so quickly and easily from person to person and are very common out in the community,” said Kath Holbourn, Director of Nursing and Governance at the hospitals, “Staff have been asked to be extra vigilant and ensure they properly wash their hands between patients and we are now asking visitors to help us too by following these simple steps.

“What we would like people to think about is whether they or anyone close to them such as family, friends or colleagues has had diarrhoea, vomiting or fever within the last 72 hours. If this is the case then they should avoid visiting the hospital and use alternative methods of contact to speak to the patient such as the hospital’s bedside telephone system. If they really feel they can’t postpone their visit they should contact the ward for advice prior to coming to the hospital.”

North Cheshire Hospitals NHS Trust

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It is believed that the generation of an exaggerated intestinal immune response to otherwise innocuous stimuli along with generation of oxygen free radicals plays a key role in the pathophysiology of UC. However, no disease-specific treatment for UC has yet emerged. Vitamin E is a major lipophilic antioxidant in cellular membranes with excellent antioxidant activities which protects membrane lipids from peroxidation by scavenging not only chain carrying peroxyl radicals but also singlet oxygen and superoxide anion radicals. This is especially interesting in case of UC, considering the pivotal role of oxygen free radicals in the genesis of mucosal damage. Given the recent evidence suggesting anti-inflammatory properties for Vitamin E, one may ask whether d-alpha tocopherol, as the dominant vitamin E isomer in plasma with the highest biopotency, can be expected to reduce the development of tissue injury in UC.

A research article published on October 21, 2008 in the World Journal of Gastroenterology addresses this question. The research team led by Dr. Mirbagheri from Department of Internal Medicine of Amir Alam hospital in Tehran-Iran, report for the first time the preliminary results of an on-going open-label case-series study on clinical and endoscopic changes of disease severity in patients with active UC who received daily rectal doses of d-alpha tocopherol for at least 12 wk.

All 15 participating patients responded dramatically to therapy after 12 weeks, with 9 of them going to clinical remission. The average score of Mayo disease activity index (DAI) started to decrease after second week and remained significantly lower for the remainder of the study. Besides, there was no case of worsening disease activity or report of serious adverse event during the course of study. The observed effect are probably due to antioxidant and anti-inflammatory effects of vitamin E which potently takes effect by local route of administration. At the end of this interesting article the authors suggest that rectal administration of d-alpha tocopherol might be used safely as a new therapeutic modality to reduce the clinical severity of ulcerative colitis without major side effects or complications of current therapies.

Reference: Mirbagheri SA, Nezami BG, Assa S, Hajimahmoodi M. Rectal administration of d-alpha tocopherol for active ulcerative colitis: A preliminary report. World J Gastroenterol 2008; 14(39): 5990-5995 http://www.wjgnet.com/1007-9327/14/5990.asp

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