1.
Chronic pancreatitis and persistent steatorrhea: what is the correct dose of enzymes?
Domínguez-Muñoz, JE
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2011;(7):541-6
Abstract
Exocrine pancreatic insufficiency with steatorrhea is a major consequence of chronic pancreatitis. Recognition of this entity is highly relevant to avoid malnutrition-related morbidity and mortality. Nutritional counseling and oral pancreatic enzyme replacement are the basis for the therapy for exocrine pancreatic insufficiency. Aim of enzyme therapy is not only to avoid symptoms but also to normalize digestion. With this aim, oral administration of pancreatic enzymes in the form of enteric-coated minimicrospheres is the therapy of choice. This enzyme preparation avoids acid-mediated lipase inactivation and ensures gastric emptying of enzymes in parallel with nutrients. Despite that, factors like an acidic intestinal pH and bacterial overgrowth may prevent normalization of fat digestion even in compliant patients. The present article reviews the current evidence on therapy of exocrine pancreatic insufficiency in chronic pancreatitis patients, with special attention to different potential endpoints to select the optimal enzyme dose for individual patients.
2.
Exercise-induced serum enzyme elevations confounding the evaluation of investigational drug toxicity. Report of two cases in a vaccine trial.
Johnson, C, Monath, TP, Kanesa-Thasan, N, Mathis, D, Miller, C, Shapiro, S, Nichols, R, McCarthy, K, Deary, A, Bedford, P
Human vaccines. 2005;(1):24-9
Abstract
Two subjects developed marked elevations in creatine kinase and other serum enzymes associated with mild myalgia during a randomized, double-blind, controlled Phase 1 clinical trial of an investigational live, attenuated vaccine against West Nile virus (ChimeriVax-WN02). One subject had received ChimeriVax-WN02 while the other subject was enrolled in an active control group and received licensed yellow fever 17D vaccine (YF-VAX). Subsequently, the clinical trial was interrupted, and an investigation was begun to evaluate the enzyme abnormalities. As daily serum samples were collected for determination of quantitative viremia, it was possible to define the enzyme elevations with precision and to relate these elevations to physical activity of the subjects, symptoms, and virological and serological measurements. Evaluation of both subjects clearly showed that skeletal muscle injury, and not cardiac or hepatic dysfunction, was responsible for the biochemical abnormalities. This investigation also implicated strenuous exercise as the cause of the apparent muscle injury rather than the study vaccines. As a result of this experience, subjects engaged in future early-stage trials of these live, attenuated viral vaccines will be advised not to engage in contact sports or new or enhanced exercise regimens for which they are not trained or conditioned. The inclusion of placebo control arm (in lieu of or addition to an active vaccine control) will also be useful in differentiating causally related serum enzyme elevations.