Studies have long shown that education is linked to better health, but new research by Pamela Herd, an associate professor of public affairs and sociology at the University of Wisconsin-Madison, shows that higher academic performance in high school plays a critical role in better health throughout life.

"How well you do in school matters," Herd says about the findings, which were published in the December issue of the Journal of Health and Social Behavior. "We already know it matters for things like your work and your earnings, but this proves it also matters for your health."

The finding may come years — or decades — after someone is in a position to do something to earn better grades. But for those who are still in school, there’s every reason to believe the link between academic performance and health exists for younger people, too, Herd says.

The conclusion relies on data from the Wisconsin Longitudinal Study, a groundbreaking survey that has involved more than 10,000 graduates of Wisconsin’s high school class of 1957 during the last 53 years. UW-Madison researchers have gone back to the class members six times since they graduated, asking questions about work, life, family and now, as the class ages, health.

The report on academic performance and health looked at links between educational attainment, high school academic performance, personality and psychological characteristics, and late-life health among high school graduates.

Herd’s findings showed that the higher a study participant’s high school rank was, the lower the probability that participant experienced worsening health between 1992 and 2003, when the class members neared retirement age.

Researchers are still working to learn more about why academic performance leads to better health outcomes.

Herd says that she thought that conscientiousness would help explain the finding. Those who are more conscientious might both do better in school and also take better care of their health.

But the data don’t support that finding, Herd says.

Instead, "what we’re seeing is what you learn in school may actually matter for your health," Herd says, adding that there could be policy implications for the study. Because the study looks at a person’s grades, "that tells us something about the consequences of emphasizing test scores over academic performance, for example, and further speaks to the importance of schooling."

Results showed that while all but one infant was protected from infection in this study, nearly 90 percent of the women — the majority of whom were immigrant or non-English speaking — did not receive education about hepatitis, further laboratory testing or subsequent care. The study also showed a surprisingly high rate of chronic HBV across this population of women of child-bearing age. These results are especially notable, said lead investigator Blaire E. Burman, MD, an internal medicine resident at Columbia Presbyterian Medical Center, because nearly 75 percent of those who screened positive were Hispanic, many from the Dominican Republic, a population overrepresented in this population, but a group not traditionally considered high risk for viral hepatitis.

The study also found that subpopulations of largely immigrant and underserved patients are living with chronic HBV and are at serious risk for morbidity and mortality. The study identified a population of young and vulnerable patients living with a chronic disease that they know little about, and are unlikely to receive the standard of care in terms of surveillance and treatment. Given the lack of follow-up testing and imaging, it is unclear what percentage of these infected women would qualify for and benefit from therapy.

Additionally, immigrant populations that are not listed as "high risk" under current screening guidelines may in fact have high rates of chronic HBV infection. It is imperative to identify carriers who do not have regular access to medical care, not just young women, but the rest of their families.

"Prenatal screening is a golden opportunity to identify chronic hepatitis B infection in young mothers at risk for life-threatening complications, including liver failure and liver cancer," Dr. Burman said. "We need to use prenatal testing to engage patients with intervention and prevention of future morbidity and mortality."

Dr. Burman added that there is very little research in this area, and no previous studies specifically looked at the follow-up of women who screened positive for HBV during pregnancy, the subsequent care received and their outcomes. She cautioned that this research applies only to the largely underserved and immigrant population

who receive prenatal care at the two urban hospitals studied, and that it cannot be applied to women with private insurance and established medical follow-up.

Dr. Burman is presenting these data May 10 at Digestive Disease Week® 2011 in Chicago.

These findings, by Rebecca Rudolph, M.D., M.P.H., and colleagues, appear today in the Annals of Internal Medicine.
An estimated 20 million Americans experience chronic heartburn that goes well beyond the occasional misery of having one too many chili dogs. About 2 million of these people have Barrett’s esophagus, a premalignant condition of the esophagus, the tube that carries food from the mouth to the stomach.

While the condition is most prevalent in middle-aged white men, the incidence of Barrett’s esophagus is rising in women and African Americans.

A physician may suspect that the condition is present if part of the inner lining of the esophagus is red rather than the usual light pink. This is determined through a procedure called endoscopy, in which a tubelike instrument is used to view the esophageal lining. However, a definite diagnosis cannot be made unless small samples of the red lining are biopsied, or removed and examined under a microscope, and found to have cellular changes typical of this disorder.

People with “long-segment” Barrett’s esophagus, in which the red lining is 3 cm or more in length, are about 40 times more likely than those in the general population to develop esophageal cancer. As a result, they typically undergo regular endoscopic screening and biopsies to ensure their condition has not progressed to cancer.

Substantially more common, however, is “short-segment” Barrett’s, in which the patch of affected tissue is no more than 3 cm long. Until recently, esophageal-cancer risk in people with shorter segments was largely unknown because such patients often were excluded from studies because their condition was more difficult to diagnose through endoscopy, and because researchers initially were uncertain whether short-segment Barrett’s indeed was a cancer risk factor at all.

Rudolph and colleagues at the Hutchinson Center and the University of Washington have found that, contrary to popular belief, the risk of esophageal cancer in patients with short-segment Barrett’s is not substantially lower than in patients with longer patches of affected tissue.

“The general feeling among gastroenterologists has been that people with short- segment Barrett’s are probably at a much lower risk of developing esophageal cancer, and so it is possible that these people aren’t being monitored as aggressively as they should,” says Rudolph, the lead author of the study.

Barrett’s-related esophageal cancer strikes about 10,000 people a year, and for unknown reasons, the incidence is rising faster than that of any other cancer in the United States. Barrett’s-related cancers tripled between 1976 and 1990, and more than doubled in the past decade. If not diagnosed early, the outlook is grim; more than 90 percent of patients with invasive esophageal adenocarcinoma die within five years of diagnosis.

The study, the largest single-center trial of its kind, involved 309 Barrett’s patients, primarily from the Puget Sound area, who were followed and closely monitored for four years.

Currently, the recommended screening frequency for Barrett’s esophagus ranges from once every three to six months to once every two to three years, depending on segment length and the degree of dysplasia, or cellular abnormality, detected under the microscope upon biopsy.

“Until more data are available, the frequency of endoscopic surveillance should be determined without regard to the patient’s segment length,” says Rudolph, a clinical specialist in the Center’s Public Health Sciences Division. “For now, people with short-segment Barrett’s should be treated exactly the same as people with long-segment Barrett’s.”

Senior authorship of the study was shared by Brian Reid, M.D., Ph.D., a member of the Center’s Clinical, Human Biology and Public Health Sciences divisions and a professor of gastroenterology at UW; and Thomas Vaughan, M.D., M.P.H., a member of the Center’s Public Health Sciences Division and a professor of epidemiology at the UW School of Public Health and Community Medicine.

This research was supported by grants from the National Institutes of Health.
Editor’s note: A copy of the paper “Effect of Segment Length on Risk for Neoplastic Progression in Patients with Barrett Esophagus” is available on the journal’s Web site, acponline, or by calling (215) 351-2656.

# # #

The Fred Hutchinson Cancer Research Center is an independent, nonprofit research institution dedicated to the development and advancement of biomedical technology to eliminate cancer and other potentially fatal diseases. Recognized internationally for its pioneering work in bone-marrow transplantation, the Center’s four scientific divisions collaborate to form a unique environment for conducting basic and applied science. The Hutchinson Center is the only National Cancer Institute-designated comprehensive cancer center in the Pacific Northwest. For more information, visit the Center’s Web site at fhcrc.

The finding, using mouse models, published in the Journal of Neuroscience February 14, suggests cardiac arrest and stroke in humans would trigger a similar chain of events.  Stroke is caused by loss of blood flow to the brain and is a leading cause of death and disability in North America. Synapses are tiny brain switches that relay information from one neuron to another. 

“Damage to the brain’s synaptic connections occurs much sooner than expected,” says Tim Murphy, UBC Professor of Psychiatry, senior investigator at the Brain Research Centre, and a member of the Vancouver Coastal Health Research Institute. “Potentially, stroke or cardiac arrest patients have undergone major changes in the structure of their synapses before anyone could think about calling 911.”

Murphy, lead author of the study says, “although stroke can be treated within three hours of onset, the implications of this study are that considerable damage – some of which is irreversible – has occurred almost immediately after a stroke. Given these results, stroke prevention through management of risk factors should be given greater emphasis.”

Using high-resolution microscopy, scientists demonstrated that the structure and function of cortical synapses were severely compromised only one to three minutes after stroke during a massive wave of electrical discharge termed ischemic depolarization. Importantly, if blood flow was restored, as can occur using stroke treatments with clot-busting drugs, 94 per cent of all synaptic connections recovered from severe deformation. Further studies will examine the upper limits of blood flow restoration time and synaptic connection recovery.

The study suggests that even short duration loss of blood flow, (approximately one to three minutes) could lead to damaged synapses.  In humans, brief loss of brain blood flow can occur during medical procedures such as bypass surgery, which can trigger blood clots to enter the brain. Other conditions with brief recurrent loss of blood flow include transient ischemia attacks, or mini strokes.  For these situations Murphy suggests, “Strategies that control ischemic depolarization associated with stroke’s effect on synapses would be fruitful avenues for future drug development.”

The work was funded by grants from the Canadian Institutes for Health Research, the Heart and Stroke Foundation of BC and the Yukon, and the Canadian Stroke Network.

Researchers from BioCentrum DTU and the Faculty of Health Sciences at the University of Copenhagen have combined the fields of Bioinformatics and ImmunoChemistry and created models of neural networks, which can do what has thus far been impossible: Simulate how the immune system defends itself from disease. The neural network models also indicate that the immune system protects itself from being deceived by microorganisms, by using ingenious PIN code-like mechanisms.

Every human being has its own unique immune system PIN code, so that even if e.g. a virus unlocks the code in one person, the knowledge gained by the virus is useless in infecting the next individual. But the same defence mechanism makes it difficult to decode the entire human immune system and develop precise immunological treatments such as vaccines.

With the new neural networks, however, Danish researchers will be able to predict all the different known, but also the as of yet unknown immune system PIN codes. This makes it the most comprehensive tool of its kind, putting the technology at the forefront of international research. 

On a global scale, the neural networks can help researchers deal with all the variables of an epidemic threat. "We’ll be able to find candidates for vaccines which can help both the individual and all of humanity," says Professor Søren Buus from the Department of International Health, Immunology and Microbiology, University of Copenhagen.

Our immune system protects us against threats from e.g. bacteria, viruses and cancer. So-called T-cells constantly inspect the body’s cells and check if they are healthy, infected or broken. T-cells can distinguish between antigens belonging to the body and those that do not. If an antigen is alien – it could originate from a virus, which has infected the cell. The T-cells can attack the sick cell and thereby remove the location of the virus and terminate the infection.

The T-cells, however, cannot see directly into other cells. To do this job, they use "samplers", called tissue type molecules, which drag fragments of everything inside the cell being investigated to its surface, and show these samples to the T-cells. Researchers have known for a long time that this selection of samples plays a key part in the workings of the immune system; if a microorganism can evade the samplers, it evades the entire immune system.

The complexity of the immune system protects against disease

To prevent microorganisms from learning how the samplers work, the immune system has furnished itself with an amazing variety of samplers or tissue type molecules. Each of us only has a few variants (our own "pin code"), but the whole of humanity has thousands.

So a microorganism can never know which samplers it encounters; and even if it does figure this out in one human, the knowledge is useless in the next person infected. This defence strategy provides one of the most sturdy ways of protecting the immune system from being infiltrated – a little like PIN codes protecting our credit cards.

If we are to understand how the T-cells work, and use this knowledge of the immune system to discover, diagnose and treat diseases, the researchers must first identify precisely those cell fragments that the samplers choose to display, since it is only if the tissue type molecules show the right part of an infected cell to the T-cell, that the immune system reacts.

Why human tissue type is vital to immunology

Today, researchers know approx. 5000 different tissue type molecules in humans and the number is increasing day-by-day. Each of us expresses a unique combination of the molecules, and this explains why two individuals never react in the same way to the diseases they encounter during their lives.

The vast number of different tissue types ("pin codes") also affect transplants, so doctors must search for optimal tissue type compatibility during e.g. bone marrow transplants, a procedure vital in treating leukaemia. If the researchers know the tissue type molecules (the "pin code") of a patient, the neural networks can map all the cell fragments his/her immune system will be presented with, and therefore which pathogens the T-cells will get to see. If e.g. a patients own immune system does not react to a disease, the new knowledge can find, isolate and produce the necessary T-cells which can see the pathogen (virus, cancer cell etc.)

This can have far reaching consequences for the treatment of cancer, infectious diseases and transplants.

The full article on this development has just been published in PloS One.

Washington D.C., August 24 — Electricity and water can be fatal. But that could be good news for consumers now that researchers have shown the deadly combination also kills bacteria like E. coli, salmonella and listeria on foods and food utensils.

“Electrolyzed water” – produced by applying an electrical current to a very dilute saltwater solution – kills bacteria on fresh produce more effectively in some cases than heat or water containing chlorine, according to a research report presented here today at the 220th national meeting of the American Chemical Society, the world’s largest scientific society.

Electrolyzed water could also be used to sanitize cutting boards, eating and drinking utensils, and food-processing equipment, says Yen-Con Hung, Ph.D., the University of Georgia professor who conducted the research. Soaking a cutting board in electrolyzed water for about five minutes at a moderately warm temperature (about 95-105 F) can reduce bacteria up to a million-fold, he says.

One advantage of using electrolyzed water to kill bacteria on food surfaces is that it doesn’t adversely affect quality as heat can, according to Hung.

Trained sensory panelists “found there was no significant effect of the treatment on the quality,” he said. They were “unable to find any differences in color, appearance or smell” between produce washed with electrolyzed water and produce washed with tap water.

The electrolytic process produces very acidic water. Hung believes the water’s low pH (acidity) and potential for oxidation-reduction contribute to its effectiveness. Essentially, oxidation-reduction involves the exchange of electrons. In the case of bacteria like E. coli, salmonella and listeria, this exchange may take away electrons needed by cell membranes for metabolism and survival.

“We think the main indicator of the effectiveness of the solution is the oxidation-reduction potential,” says Hung. “When you compare chlorinated water with electrolyzed water, there is a difference in the oxidation-reduction potential, even though they have the same chlorine concentration.” The exact role of oxidation-reduction in destroying bacteria is still being investigated, he says.

Chlorine is not physically added to electrolyzed water, but is produced when the electrical current passes through the water and salt mixture. The chlorine that is generated “is definitely one of the major components for killing microorganisms,” Hung acknowledges. But, he adds, electrolyzed water has additional active components – oxidants – that his research group is trying to identify.

The equipment needed to produce and treat food with electrolyzed water is compact and already produced by several companies in Japan. A typical unit costs between $3,000 and $5,000, says Hung. He believes the food industry will be first to use electrolyzed water and then, as equipment costs come down, consumers will use it at home.

A fast-food chain in the United States is testing the technology and several other companies have expressed interest, according to Hung. He did not identify them.

A few U.S. water treatment plants already use technology similar to that tested, according to Hung.

The research paper, AGFD 133, will be presented at 10:50 a.m., Thursday, Aug. 24, in the Washington Convention Center, Room 11-12.

Yen-Con Hung, Ph.D., is a professor in the department of food science and technology at the University of Georgia in Griffin, Ga.

A nonprofit organization with a membership of 161,000 chemists and chemical engineers, the American Chemical Society publishes scientific journals and databases, convenes major research conferences, and provides educational, science policy and career programs in chemistry. Its main offices are in Washington, D.C., and Columbus, Ohio.

"We hope the ideas put forward in this article will stimulate additional experiments to test these novel concepts," said Arnold Levine, Ph.D., co-author of the study from the Institute for Advanced Study in Princeton, New Jersey. "Among those experiments are the synthesis of new drugs to inhibit pathways that could change the course of a disease."

After a review of existing experimental literature, Levine and colleagues concluded that a new class of drugs could be developed to address the conflicting nature of oncogenes and tumor suppressor genes. Specifically, the research paper published in The FASEB Journal examines the roles of the p53 tumor suppressor and the oncogene, NF-kappaB. The p53 suppressor limits the consequences of stress by initiating cell death and promoting metabolic patterns in the cell. The oncogene NF-kappaB on the other hand, promotes cell division resulting in the synthesis of substrates for cell division. These two cellular responses, both of which have evolved to handle different types of stress, have adopted opposite strategies and cannot function in the same cell at the same time. As a result, Levine and colleagues speculate that drugs could be developed to take advantage of the fact that if one factor is activated, the other is rendered inactive. This could be achieved at several places in both the p53 and NF-kappaB pathways where regulatory proteins act on both with opposite functional consequences.

"Our cells use the p53 and NF-kappaB pathways to respond to cellular stress: one controls cancer, the other immunity. If they get out of balance, we’re in trouble.," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "Thanks to this work we can start restore the balance by means of new drugs."

Because individuals with both depression and bipolar disorder experience a glutathione deficiency, an antioxidant that protects cells from toxins, researchers in a new study scheduled for publication in the September 15th issue of Biological Psychiatry sought to evaluate whether N-acetyl cysteine (NAC), an over-the-counter supplement that increases brain glutathione, might help alleviate depressive symptoms.

Dr. Michael Berk and colleagues, in a randomized, double-blind, placebo-controlled trial, evaluated the mood symptoms of individuals with bipolar disorder, half of whom received placebo and half of whom received NAC, as an add-on therapy to their usual treatment.

Over the 24 weeks of the study, NAC was well tolerated, and induced a marked and significant improvement in depressive symptoms. Ashley Bush, M.D., Ph.D., the article’s corresponding author, further explains: “Glutathione is the brain’s primary antioxidant defense, and there is evidence of increased oxidative stress in bipolar disorder. Therefore, we studied the potential benefit of NAC treatment in bipolar disorder and found that it impressively remedied residual depressive symptoms.”

John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, comments: “The preliminary evidence of efficacy of NAC is very interesting.

This study might suggest a number of novel approaches to treating depression. In subsequent efforts to replicate this preliminary finding, it will be important to determine how much NAC reaches the brain after oral administration.”

As noted by both the authors and Dr. Krystal, additional studies will be necessary to further evaluate and replicate these findings. However, as Dr. Berk observes, “Brain glutathione metabolism appears to be a valuable new treatment target for psychiatric disorders, and we hope the impressive results of this study opens up a new treatment option.”

The finding implicates the cytokine molecule interleukin-17, and supports the burgeoning theory that an immune response plays a significant role in disc disease, says William J. Richardson, MD, an orthopedic surgeon at Duke. It may also open the door for new, therapeutic approaches that target a specific immune response in hopes of halting disc destruction, and possibly reversing the disease process.

"By identifying the specific subpopulation of lymphocytes (immune cells that are excited into action by the cytokine), it may soon be possible to arrest the body’s inflammatory response to disc cells," says Richardson, senior author of the research published online in the July issue of Arthritis and Rheumatism. Doing so could reduce the painful inflammation associated with degenerative disc disease, and halt the evolution of arthritis. It may also reduce the need for back surgery.

"Mechanical forces may initiate the degenerative process, but biochemical inflammatory changes certainly play a role in disc pathology," says the study’s first author, Mohammed Shamji, MD, PhD, senior neurosurgery resident at The Ottawa Hospital, Ontario, Canada, who participated in the research while at Duke. Decreasing the inflammation may arrest or reverse the patient’s disease process and perhaps reduce the need for surgery. "Now we are learning which pathways we have to block."

Low back pain is one of the most common reasons people seek medical care, and both degenerative and herniated discs — also referred to as slipped discs or ruptured discs — are common causes of that pain. The economic impact of medical care for herniated discs in the U.S. is estimated to be as high as $200 billion per year.

Herniated discs occur when the tough outer layer of cartilage cracks, allowing pieces of the softer inner material to protrude into the spinal canal. Until recently, it was thought that pain occurs when the material touches a nerve. Now doctors believe the pain is the result of an immune response caused by the presence of inflammatory cells.

"The center of the disc is immune-privileged since it has never been exposed to the immune system," says Shamji. When a disc is injured or degenerates, the body reacts against the invading inner material as it would against any virus or foreign body, and launches a response targeted at destruction. The nerve root, which is present near the protruding disc material, becomes painfully inflamed, swollen and damaged during that cascade of events.

In recent years, several anti-immune therapies, including steroids, have been injected into the space between the disc and the nerve, but with limited success, doctors say, because they don’t target a specific immune response, and because low doses are used to minimize potentially serious side effects that include a higher predisposition to infection, activation of tuberculosis and a six-fold increase in lymphoma incidence.

The identification of IL-17 in the cascade of events is significant, Shamji says. "It’s a product of a specific subgroup of immune cells that are involved in auto immune phenomena like rheumatoid arthritis and asthma, but not in the body’s response against infection or tumor. If you target this specific lymphocyte, you may avoid compromising the body’s ability to protect itself against infection or tumor."

Researchers say they’re still several steps away from human studies of IL-17 blockers currently in development.

Non-steroidal anti-inflammatory drugs (NSAIDs) are an important part of the pharmaceutical treatment of pain and inflammation and have shown promise in providing a protective effect from cancer. However, there are dose-dependent safety concerns related to cardiovascular impact, bleeding risks and gastrointestinal distress related to the use of NSAIDs.

"The medical community has traditionally been skeptical about the use of NSAIDs," according to Byron L. Cryer, MD, associate professor of internal medicine at the University of Texas Southwestern Medical Center. "These new findings suggest the need to further investigate the potential effects of additional low-dose and combinational applications for NSAID medications, which seem to be proving effective in preventing disease."

Chemopreventive Effectiveness of Celecoxib Two Years After Cessation of Treatment

Unless detected early, the mortality rate for colon cancer is high. With colon cancer screening rates only at about 30 percent in the U.S., additional options to prevent colon cancer are eagerly sought. In this three-year, randomized, placebo-controlled, double-blind study, investigators sought to determine if the use of a chemopreventive drug could reduce adenoma (benign tumor) burden.

The study followed 1,561 adenoma-prone patients in 32 countries to determine if patients treated with a single 400-mg daily dose of celecoxib (twice the approved osteoarthritis dose) had lower rates of benign polyps than those treated with a placebo. Celecoxib has previously demonstrated efficacy in preventing adenomatous polyp recurrence, however, questions have been raised about the cardiac profile of celecoxib and other common prescription arthritis pain relievers.

For those randomized to celecoxib, 400 mg daily, relative risk (RR) of new adenomatous polyp was 0.64 (95 percent confidence interval [CI], 0.56–0.75); p < 0.001) and that for advanced adenomatous polyp was 0.49 (95 percent CI, 0.33–0.73; p < 0.001) through year three compared with placebo.

Additionally, no statistically significant difference was found in the rate of side effects between the two groups at year three. When concerns over cardiovascular risk prompted cessation of drug administration based on results from another adenoma prevention study, 1,043 subjects were given the option to continue safety assessments for at least two years after treatment ended and undergo a final colonoscopy at year five.

Overall, the cumulative five-year rate of detecting any adenomatous polyp and that of detecting advanced adenomatous polyp were lower in the celecoxib 400 mg daily group (RR, 0.75; 95 percent CI, 0.65–0.86; p < 0.0001), and that for advanced adenomatous polyp detection was 10 percent in the celecoxib group and 13.8 percent in the placebo group (RR, 0.64; 95 percent CI, 0.457–0.887; p = 0.0072). However, the proportion of subjects with new adenomatous polyp, at year five only, was higher in the celecoxib group.

Over the five years of the study, including approximately three years on treatment and two years off treatment, cardiac disorders occurred in 10.4 percent of patients randomized to celecoxib 400 mg and in 6.5 percent of those randomized to placebo. In the two years off treatment very few serious cardiac disorders occurred (1 percent placebo, 1.4 percent celecoxib). Subjects who received celecoxib 400 mg experienced a slightly higher rate of adverse (77.9 percent vs. 75.4 percent for placebo) and serious adverse events (23.9 percent vs. 20.6 for placebo) over the five-year study period.

These data, together with additional new placebo-controlled analyses of celecoxib cardiovascular safety, suggest that chemoprevention with celecoxib may be safe and effective for some high risk colorectal adenoma patients with low cardiovascular risk.

"We know the drug is effective to reduce the incidence and recurrence of adenoma," said Nadir Arber, MD, head of the Integrated Cancer Prevention Center at Tel Aviv Medical Center, Tel Aviv University, Israel. "However, advances are needed to either use the drug in lower doses or develop combination therapy that can produce the same effect without the adverse side effects."

A Meta-Analysis of Rectal NSAIDs in the Prevention of Post-ERCP Pancreatitis

Endoscopic retrograde cholangiopancreatography (ERCP) is a procedure by which a physician can enter through the mouth to perform interventions on the bile ducts and pancreas. This common procedure, however, may injure or cause inflammation to the pancreas causing pancreatitis, in which the patient may suffer from abdominal pain, nausea, vomiting, further hospitalization and, in extreme cases, death.

Several studies have investigated ways to prevent pancreatitis following ERCP, predominantly through the use of medications given to the patient at the time of the procedure. This meta-analysis examined the potential protective effect of NSAIDs in the prevention of pancreatitis following ERCP.

Researchers aggregated the data from four clinical trials, with a total of 912 patients examined. They then combined the results statistically. The investigators found that overall, there was indeed a protective effect found through NSAID use at the time ERCP is performed. Patients who received NSAIDs during the procedure were 64 percent less likely to develop pancreatitis and 90 percent less likely to develop moderate to severe pancreatitis.

"The ERCP community has been skeptical about adopting the use of NSAIDs during ERCP because of prior lack of efficacy of other agents and concerns that the drug may cause bleeding," said B. Joseph Elmunzer, MD, division of gastroenterology, University of Michigan Medical Center. "However, our study suggests that if a single dose of NSAID is given at the time of ERCP, there is a protective effect and it doesn’t appear to increase the risk of bleeding."

The study found that 15 patients needed to be treated with NSAIDs to prevent one case of pancreatitis. It should be noted that of the four trials aggregated for this study, two enrolled only high-risk patients and two enrolled a more general population of patients. Additionally, the studies looked at the effects of two different NSAIDs — diclofenac and indomethacin.

Combinational Chemoprevention Using Low Dose Aspirin and Urso in Barrett’s Mucosa

A combination of Urso and aspirin is successful in preventing the development of esophageal adenocarcinoma in rodents, resulting in a cancer risk reduction of 58 percent, compared to other approaches. Esophageal cancer related to heartburn is one of the most rapidly increasing cancers in Western countries and leads to 10,000 deaths in the US each year. Urso modifies bile salt composition and possesses chemoprevention potential in vivo.

Researchers are trying to find the explanation for the rapid rise in this type of esophageal cancer. It is speculated that the aging population, rise in obesity and inadequately treated heartburn may contribute to the development of this cancer. Esophageal cancer is closely linked to heartburn, in which acid and bile from the stomach and intestines regurgitate into the food pipe and damage its lining. Unfortunately, this cancer is deadly and only 10 to 15 percent of patients diagnosed with this cancer survive for five years. Treatment options are limited. Surgery entails removing the food pipe, which is a major undertaking and compromises the patient’s quality of life.

When healthy patients are treated with Urso, especially patients with liver disease, it greatly reduces the concentration of toxic, carcinogenic bile. Also, researchers found that patients who take drugs to decrease injury or inflammation like aspirin are less likely to be diagnosed with this cancer.

Navtej S. Buttar, MD, assistant professor of medicine in the department of gastroenterology at the Mayo Clinic, Minnesota, explored whether a combined approach of Urso and aspirin would be beneficial. "We wanted to approach both the cause and the consequence at the same time," he said.

This combined approach could be more effective and perhaps safe, too. "There are different pathways through which cancer can escape, so you need to block more than one road leading to that progression," Buttar said. "If you can block the effect of cancer-promoting bile by using Urso, you could see a better effect than just using aspirin alone." Conversely, using only Urso may not be that promising because while it lowers bad bile salts, it also raises an enzyme — COX2 — which may cause inflammation.

For this study, investigators gave rodents heartburn, which ultimately led to cancer. They treated the rodents with a combination of low doses of Urso and aspirin. The result was a reduction in cancer risk of nearly 60 percent. Investigators researched the cancer cells of Barrett’s esophagus and exposed them to the dual combination as well and found it be highly effective in decreasing the number of any surviving cancer cells.

Dr. Buttar said the combination also caused the immortal cells to age and die off. "If we can use pathways to cause aging in cancer cells and make them quiet, they’re probably not going to grow into big tumors," he said.