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Unexpected Consequences Of Proton Pump Inhibitor Use In Reflux Disease

According to the authors, gastroesophageal reflux(GERD) and laryngopharyngeal reflux (LPR) are diseases that have undergone a remarkable growth in public health relevance over the last 20 years. While it has been known historically that more than 50 percent of adults in Western countries have occasional symptoms of reflux, there has been a more than four-fold increase in how many patients seek medical care for their symptoms.

PPIs are a class of important and generally safe medicines that prevent the release of stomach acid, which is one cause of the burning sensation many reflux patients experience. PPIs are among the most widely prescribed classes of medications for GERD and LPR diseases. But according to the authors, there is a growing body of literature demonstrating that acid is not the only causal agent of tissue damage in reflux disease, and that PPIs are not effective at treating all cases of GERD and LPR.

In addition to the evidence that acid isn't the only contributing agent in reflux disease, the authors' search of recent research on PPIs pointed out that there are many unexpected consequences and side effects from this class of drugs. They can include: increased rates of hip fractures, possibly related to altered calcium absorption; possible but yet unproven altered vitamin B12 and iron absorption, related to alteration of the gastric pH; increased odds of acquiring nosocomial Clostridium difficile-associated diarrhea; and increased odds of contracting community-acquiredpneumonia.

The authors say while it may be premature to make global recommendations about PPI prescribing patterns, they applaud the idea of raising clinical awareness of this medication class and its potential unexpected consequences. In addition, appropriate evaluation and monitoring of patients taking PPIs will be important in determining the need and duration of the use of the medications. The authors further advise physicians treating reflux disease patients to weigh the risks of treatment versus the risks of not treating the disease, and to consider a goal of a more holistic approach that includes diet and lifestyle modification. These additional steps could prove beneficial in lowering healthcare costs associated with reflux diseases, and encourage patients to continue practicing behaviors that would improve their overall health.

New Targets Found For Preventing Diabetes Complications

In diabetes patients, high blood glucose levels can end up killing certain cells in the eyes and kidneys, which is why diabetes is the leading cause of adult blindness and of kidney failure. Years ago, scientists identified one main route for this destruction-high glucose produces oxidativestress through the NF-kB molecular pathway-but success has been elusive for drugs targeting that pathway.

Researchers at Joslin Diabetes Center now have clarified the complications story by detecting a second, independent pathway, which offers new targets for preventing and treating diabetic eye disease.

"Previously it was thought that oxidants are the major pathway, but antioxidants don't seem to work in clinical trials," notes George L. King, M.D., Joslin's Director of Research, head of the Dianne Hoppes Nunnally Laboratory and senior author on the paper reporting the discovery in Nature Medicine's November issue.

"That clinical observation made it clear that we don't know all the mechanisms involved," says Pedro Geraldes, Ph.D., lead author for the paper and a postdoctoral researcher in the King lab. Expanding the search for what goes wrong as glucose levels climb, Geraldes studied the effects on retinal pericytes (supportive tissue cells found near small blood vessels).

Scientists had long known that the protein PDGF, a growth factor, is essential to a cell-survival pathway that is required to keep these retinal cells alive. Working both in cultured cells and diabetic animals, Geraldes traced a molecular cascade that ends up increasing the expression of a novel target, the protein SHP-1, which de-activates PDGF activity and thus triggers cell death.

"What's exciting is that we finally have an explanation for why antioxidant drugs may not work, because there's a parallel pathway," says King, who is also Professor of Medicine at Harvard Medical School. "We'll need an inhibitor of SHP-1 together with antioxidants to have a realistic chance of preventing or stopping diabetic eye disease."

"We think this is also applicable to diabetic kidney disease, because we observed a similar increase in SHP-1 in the kidneys of diabetic animals," King adds. Additionally, understanding the role that SHP-1 plays in cell survival pathways may shed light on studies of cancer and other diseases, he says.

In follow-up research, Joslin scientists and their colleagues will test the mechanism in human cells and work on potential therapies based on targeting SHP-1.

Funding for the research came from the National Eye Institute, the Canadian Institutes of Health Research and the Juvenile Diabetes Research Foundation.

Others participating in the research include Junko Hiraoka Yamamoto, Ph.D., Motonobu Matsumoto, Ph.D., Allen Clermont and Lloyd P. Aiello, M.D., Ph.D., of Joslin; Michael Leitges, Ph.D., of the University of Oslo; Andre Marette, Ph.D., of Université Laval; and Timothy S. Kern, Ph.D., of Case Western Reserve University.

Activation of PKC-delta and SHP-1 by hyperglycemia causes vascular cell apoptosis and diabetic retinopathy, Geraldes, P. et al, published online by Nature Medicine at 1 p.m. on November 1, 2009. DOI: 10.1038/nm.2052.

Levofloxacin effective in chronic pulmonary infection in cystic fibrosis

A study carried out by the company, Mpex Pharmaceuticals, Inc., San Diego, California, has examined the in vitro pharmacodynamics of levofloxacin and other aerosolized antibiotics for the treatment of chronic pulmonary infection associated with cystic fibrosis.
They found that in a number of cases levofloxacin was more potent than aminoglycosides or aztreonam. They also found that high concentrations of levofloxacin could be easily achieved in the lung by aerosol delivery and suggest this for the management of infections in the lungs of cystic fibrosis patients.

Levofloxacin continues to be effective against P. aeruginosa under anaerobic and hypoxic conditions

A study carried out by investigators at Mpex Pharmaceuticals, Inc., San Diego, California, examined the treatment of Pseudomonas aeruginosa in patients with cystic fibrosis. Previous studies have shown that the thickened mucous layers in the lungs of such patients may reduce the efficacy of aerosol antibiotics used to treat chronic infections in CF.
The study compared the MIC values for levofloxacin, tobramycin, amikacin and aztreonam against P. aeruginosa. Although the activity of tobramycin, amikacin and aztreonam was significantly reduced under conditions similar to the CF lung environment, levofloxacin maintained its activity under both anaerobic and hypoxic conditions which were likely to be found in the microaerophilic environments of CF lungs

Type 2 Diabetes: Prevention Or Delay With Lifestyle Intervention Or Metformin Lasting At Least 10 Ye

An article published Online First and in a future edition of The Lancet reports that prevention or delay of type 2diabetes with lifestyle intervention or metformin can persist for at least ten years. The article is the work of Dr. William C. Knowler of the U.S. National Institute of Diabetes and Digestive and Kidney Diseases and colleagues from the Diabetes Prevention Program Research Group.
They write in conclusion: "Our results have shown that a reduction in diabetes cumulative incidence by either lifestyle intervention or metformin therapy persists for at least 10 years. Further follow-up will provide crucial data for long-term clinical outcomes, including mortality... The long-term reductions in bodyweight and diabetes are encouraging, but further quantification of long-term outcomes is crucial to establish the benefits of diabetes prevention."

In a supplementary comment, Dr Anoop Misra, Department of Diabetes and Metabolic Diseases, Fortis Hospitals, New Delhi, India, remarks: "Prevention of diabetes is a long and winding road. There seems to be no short cut, and a persistent and prolonged intensive lifestyle intervention seems to be the most effective mode to travel on it. However, more research needs to be done with dietary (eg, high-fibre, low-glycaemic-index foods), physical activity (aerobic plus resistance exercise), and pharmaceutical (especially glucagon-like peptide-based therapies) manipulations to prevent diabetes. We need more effective drugs for those who cannot follow intensive lifestyle therapy because of infirmity. Because of the high prevalence and rapid increase in the metabolic syndrome and diabetes, there is a need to apply these findings to, and generate data from, other ethnic groups and developing countries."

WHO Identifies Five Major Causes Of Premature Death

Targeting the five major causes of premature death could increase global life expectancy by almost five years, the WHO said Tuesday, Reuters reports. According to a WHO's Global Health Risks report, which looked at 24 major health risks, "poor childhood nutrition, unsafe sex, alcohol, bad sanitation and hygiene, andhigh blood pressure are to blame for around a quarter of the 60 million premature deaths around the world each year," the news service writes.

"The poorest countries still face a high and concentrated burden from poverty, undernutrition, unsafe sex, unsafe water and sanitation," the report said. "The report warned that although some major health risk factors, such as smoking, obesity and being overweight, were usually associated with high-income countries, more than three-quarters of the total global burden of diseases they cause now occurs in poor and developing countries," Reuters writes (Kelland, 10/27).

New Procedure For Acid Reflux/GERD

Boston Medical Center (BMC) surgeons are now offering patients an incisionless alternative to laparoscopic and traditional surgery for treatment of acid reflux or GERD.

Using the new procedure known as EsophyX TIF (Transoral Incisionless Fundaplication), surgeons can repair or reconstruct the valve between the esophagus and stomach, effectively stopping GERD. BMC is the only hospital in New England offering this new treatment.

Improving Cognitive Skills With Music

Regularly playing a musical instrument changes the anatomy and function of the brain and may be used in therapy to improve cognitive skills.

There is growing evidence that musicians have structurally and functionally different brains compared with non-musicians. In particular, the areas of the brain used to process music are larger or more active in musicians. Even just starting to learn a musical instrument can changes the neurophysiology of the brain.

Lutz Jäncke, a member of Faculty of 1000 Medicine, proposes using music in neuropsychological therapy, for example to improve language skills, memory, or mood. In a review for Faculty of 1000 Biology Reports, an online publication in which leading researchers highlight advances in their field, Jäncke summarizes recent studies of professional musicians.

The brain regions involved in music processing are also required for other tasks, such as memory or language skills. "If music has such a strong influence on brain plasticity," writes Jäncke, "this raises the question of whether this effect can be used to enhance cognitive performance."

Several studies indeed show that musical practice increases memory and language skills, and Jäncke suggests expanding this field: "Hopefully, the current trend in the use of musicians as a model for brain plasticity will continue ... and extend to the field of neuropsychological rehabilitation."

New Procedure For Acid Reflux/GERD

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