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OBJECTIVE: To determine whether two applicants who misrepresented their accomplishments in applications for gastroenterology fellowships reflected isolated incidents or whether misrepresentation was more wide-spread. DESIGN: Retrospective review of all 236 applications submitted for fellowship in a recent year for confirmation of research experience and cited publications. RESULTS: 138 applicants (58.5%) reported research experience during residency in a U.S. training program. Research activity could not be confirmed for 47 of 138 applicants (34.1%). Fifty-three applicants (22.4%) reported published articles, and 16 of these applicants (30.2%) misrepresented articles. Misrepresentation included citations of nonexistent articles in actual journals, articles in nonexistent journals, or articles noted as "in press." CONCLUSIONS: Misrepresentation on applications for gastroenterology fellowships was common. The following steps are recommended: 1) Fellowship programs should require that copies of all publications and letters of acceptance for manuscripts in press be submitted with fellowship applications; 2) applications should contain a statement to be signed by the applicant that the information provided is accurate; 3) persons writing letters of recommendation should verify the information being submitted by applicants; 4) medical students and residents should be taught that embellishment of curricula vitae constitutes misconduct; and 5) institutions and professional organizations should develop policies to deal with this problem.

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In an effort to identify the effects of the 3-carbon compound pyruvate on free radical production, we measured hepatic total peroxisomal beta-oxidation and catalase activity and the production of lipofuscin-like products in male Sprague-Dawley rats consuming an adequate diet supplemented with pyruvate, vitamin E, or the peroxisome proliferator and free radical enhancer clofibrate for 22 days (n = 5 in each group). Clofibrate feeding induced hepatomegaly, a fivefold increase in total peroxisomal beta-oxidation activity, and a threefold increase in hepatic lipofuscin-like products (P < .05). Pyruvate but not vitamin E inhibited the increase in liver size by 70% (P < .05). Both pyruvate and vitamin E completely inhibited clofibrate-induced increases in lipofuscin-like products (P < .05). Pyruvate but not clofibrate or vitamin E increased plasma concentrations of the nitric oxide metabolites nitrite and nitrate (P < .05). We conclude that with clofibrate-induced peroxisomal proliferation and free radical production, pyruvate will inhibit peroxisomal proliferation and free radical production, inhibit free radical-induced lipid peroxidation, and enhance metabolism of nitric oxide.

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PEG (percutaneous endoscopic gastrostomy) tubes are frequently placed in nursing home patients. The aim of this study was to assess retrospectively the long-term changes in functional and nutritional statuses, tube-related complications, and factors influencing survival in 46 nursing home residents, mean age 73.6 years (range 19-96). Functional status was evaluated by a standard rehabilitation medicine scale. Nutritional status was evaluated by serum albumin and cholesterol concentrations and by weight. PEG-related complications requiring hospitalization or emergency room or clinic evaluations were noted. Additionally, changes in resuscitation status were noted. The predominant indication for PEG placement was dementia (52%). At PEG placement, 48% of patients had total functional impairment. Regardless of the severity of impairment, no patient's functional status improved after PEG. Nutritional status did not improve significantly. Mortality approached 50% and 60% at 12 and 18 months, respectively, and was significantly related to age, resuscitation status, and serum albumin concentration. All patients under 40 years of age at PEG survived, in contrast to 41.3% of patients over 40 years of age (P < 0.001). Sixty-three percent of patients who were "full code" at PEG placement survived, in contrast to 10% of "no code" patients (P < 0.001). Albumin > or = 3.5 g/dl at PEG or thereafter was associated with improved survival (P < 0.001) as compared to albumin < 3.5 g/dl. PEG-related complications occurred in 34.7% of patients, and the first occurred four months after PEG. We conclude that realistic expectations of what PEG can accomplish be a factor in the decision to place a PEG tube in nursing home patients.

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Hepatic peroxisome proliferation is induced by a number of agents, including clofibrate. Sustained proliferation of peroxisomes is associated with the development of hepatocellular carcinoma. In the present study, we have investigated the role of testosterone in peroxisome proliferation induced by clofibrate. Three groups of male rats (intact, castrated, and castrated replaced with testosterone) were studied. Proliferation of peroxisomes was induced by feeding clofibrate (0.25%, 0.50%, and 1.0% of diet) for 2 weeks. Peroxisome proliferation was monitored by measuring total peroxisomal beta-oxidation activity. In intact rats, the peroxisomal beta-oxidation activity (nmol/min/mg protein) increased in a dose-dependent manner and was 7.2 +/- 0.4, 52.6 +/- 7.5, 63.2 +/- 3.7, and 92.4 +/- 4.0 at clofibrate doses of 0%, 0.25%, 0.50%, and 1.0%, respectively. In contrast, in castrated rats, the total peroxisomal beta-oxidation activity was significantly (P < .01) lower at clofibrate levels of 0.25% and 0.50% (25.8 +/- 2.7 and 42.5 +/- 2.2, respectively), but not at the clofibrate level of 1.0% (85.0 +/- 6.3). Testosterone replacement of castrated rats restored the peroxisomal beta-oxidation activity. To determine whether the above results were related to the metabolism of clofibrate in the absence or presence of testosterone, we measured serum clofibrate levels. These levels were 50% lower in castrated rats than in intact rats or in testosterone-treated castrated rats. The activity of hepatic uridine diphosphate (UDP)-glucuronyltransferase, the enzyme catalyzing the glucuronidation of clofibrate, was measured using either bilirubin or 4-methylumbelliferone as substrates and was found to be unaffected by castration or testosterone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

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The prevalence of clinically relevant bacteremia after endoscopic procedures in bone marrow transplant recipients was assessed retrospectively. Bacteremia, within 24 hr of procedure, was defined as positive blood cultures, while hypotension and temperature greater than 38 degrees C were taken as possible indicators of bacteremia. Sixty-seven procedures were performed in 53 endoscopic sessions (upper endoscopy 37, flexible sigmoidoscopy 7, upper endoscopy + flexible sigmoidoscopy 8, colonoscopy 1). Twenty-five endoscopic sessions were performed in patients receiving broad-spectrum antibiotics and 28 sessions in patients not receiving antibiotics. Both groups were comparable with respect to patient characteristics, procedures performed, and immune status. No patient in either group developed hypotension. One patient developed fever after flexible sigmoidoscopy; no source of fever was identified. We conclude that: (1) there were no episodes of clinically relevant bacteremia attributable to endoscopic procedures, and (2) not all bone marrow transplant recipients require routine antibiotic prophylaxis prior to endoscopic procedures.

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1. Rat liver was fractionated into peroxisomes and mitochondria and branched-chain keto acid (BCKA) dehydrogenase activity was measured. 2. All BCKA dehydrogenase activity was associated with the mitochondrial fraction and none with the peroxisomal fraction. 3. BCKA dehydrogenase was also not detected in hepatic peroxisomes of rats treated with clofibrate which induces several peroxisomal enzymes. 4. Hepatic peroxisomes from rabbit, hamster and dog also did not show any BCKA dehydrogenase activity. 5. We conclude that mammalian hepatic peroxisomes do not contain BCKA dehydrogenase.

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We recently reported that purified carnitine acetyltransferase is competitively inhibited by bile acids (Sekas, G. and Paul, H.S. (1989) Anal. Biochem. 179, 262-267). In the present study, we initially investigated the effect of bile acids on carnitine acyltransferases in rat hepatic peroxisomes. Activities of carnitine acetyltransferase, carnitine octanoyltransferase, and carnitine palmitoyltransferase were progressively inhibited by increasing concentrations of chenodeoxycholic acid. Kinetic studies revealed that the inhibition by chenodeoxycholic acid was competitive with respect to carnitine with an apparent Ki of 890 microM for carnitine acetyltransferase, 650 microM for carnitine octanoyltransferase and 600 microM for carnitine palmitoyltransferase. We then investigated whether bile acids inhibit the activities of these enzymes ex vivo. The hepatic concentration of bile acids was increased by inducing cholestasis by bile duct ligation. Cholestasis reduced the activity of carnitine acetyltransferase, carnitine octanoyltransferase, and carnitine palmitoyltransferase to 66 +/- 2%, 64 +/- 3%, and 40 +/- 2%, of the control, respectively. The inhibition for each of these enzymes was proportional to the degree of cholestasis. The effect of cholestasis appeared specific for carnitine acyltransferases since the activity of catalase, another peroxisomal enzyme, was not affected by cholestasis. We conclude that bile acids inhibit the activities of carnitine acyltransferases in hepatic peroxisomes. This inhibition by bile acids may be of significance in cholestatic liver disease.

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The release of carnitine is an important metabolic function of the liver. In the present study, we have investigated the effect of increased carnitine concentration on the hepatic release of carnitine. Hepatic carnitine concentration was increased in rats by clofibrate treatment. Release of carnitine was investigated as its efflux from perfused liver and its secretion into bile. A significantly smaller proportion of the hepatic pool of carnitine was released into the perfusion medium when carnitine concentration was increased by clofibrate treatment. However, the amount of carnitine released (nmol/g liver) was comparable to that of control rats. Increased carnitine concentration by clofibrate treatment also did not affect the rate of biliary secretion of carnitine. In control rats, nearly 50% of the released carnitine, in both the perfusion medium and bile, was acylcarnitine whereas in clofibrate-treated rats 35% of the released carnitine was acylcarnitine. Release into the perfusion medium was the major route for the hepatic export of carnitine. We conclude that when hepatic carnitine concentration is increased by clofibrate treatment, a smaller proportion of the hepatic carnitine pool is released, but the amount of carnitine released (nmol/g liver) is not greatly different than that from control animals.

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We have investigated whether hepatic peroxisomes are capable of synthesizing carnitine. When purified peroxisomes were incubated with gamma-butyrobetaine, a precursor of carnitine, formation of carnitine was observed. These results indicate that peroxisomes contain gamma-butyrobetaine hydroxylase, the enzyme which catalyzes the final step in the biosynthesis of carnitine. This enzyme was previously believed to be present only in the cytosol. gamma-Butyrobetaine hydroxylase activity in peroxisomes was not due to cytosolic contamination as evaluated by marker enzyme analysis. When proliferation of peroxisomes was induced by clofibrate treatment, gamma-butyrobetaine hydroxylase/mass liver increased by 7.6-fold and the specific activity by 2.5-fold. We conclude that hepatic peroxisomes synthesize carnitine and this synthesis becomes substantial under conditions of peroxisomal proliferation.

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Partial obstruction of the common bile duct was produced in rats by tightly tying a 0.5 mm stainless steel rod to the proximal common bile duct. The rod was then removed from the ligature leaving a constriction around the duct. Within 2 weeks the bile duct proximal to the partial obstruction was markedly dilated. Liver histology was notable for marked proliferation of the interlobular bile ductules and minimal cholangitis, changes which are characteristic of partial obstruction.

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A 37-yr-old white man experienced crampy abdominal pain beginning 21 days after successful bone marrow transplantation for chronic myelogenous leukemia. Generalized edema and hypoproteinemia developed. Symptoms persisted until 61 days post-transplant, when the patient developed an acute abdomen. At laparotomy, an edematous segment of jejunum was resected. Pathological examination showed submucosal vasculitis and necrotizing enteritis. Serum protein and albumin levels returned to normal within a few weeks after surgery. Vasculitis of the gastrointestinal tract should be considered in the differential diagnosis of protein-losing enteropathy after bone marrow transplantation.

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Carnitine acetyltransferase is used in a radioenzymatic assay to measure the concentration of carnitine. While determining the concentration of carnitine in rat bile, we found that the apparent concentration increased as bile was diluted (6.7 +/- 1.0 and 66.6 +/- 9.4 nmol/ml in undiluted and 20-fold diluted bile, respectively). The present study was designed to investigate whether a component of bile inhibited carnitine acetyltransferase. Inhibition was evaluated by measuring carnitine concentration in bile or by determining the recovery of a known amount of carnitine in the presence of bile. Inhibitory activity was extractable in organic solvents, stable to heat and base treatments, resistant to trypsin and lipase digestions, and removable by cholestyramine, a bile acid-binding resin. These results suggested that the inhibitory activity was associated with bile acids. Direct evidence was obtained by showing a reduced detectability of carnitine in the presence of individual bile acids. Chenodeoxycholic acid was the most potent inhibitor. Inhibition was unrelated to the detergent properties of bile acids. Kinetic studies revealed that carnitine acetyltransferase was inhibited competitively by chenodeoxycholic acid with a Ki of 520 microM. Bile acids also interfered in the quantitation of carnitine in cholestatic plasma. Carnitine concentration in such plasma was underestimated (17.5 +/- 2.1 mmol/ml). Reduction of bile acid concentration by a 20-fold dilution of cholestatic plasma resulted in a 3-fold higher carnitine concentration (54.6 +/- 9.0 nmol/ml). Results demonstrate that, because of the inhibition of carnitine acetyltransferase by bile acids, the radioenzymatic assay will underestimate carnitine concentration in bile or in cholestatic plasma. Accurate measurement requires either the removal of bile acids or a marked reduction in their concentration.

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A 31-year-old woman presented with constant epigastric pain. Obstruction of the pancreatic duct was observed by ultrasonography and CT scan and was further defined by ERCP. Surgical exploration of the pancreas revealed a tumor in the pancreatic head. Histologic and immunocytochemical examination revealed a benign granular cell tumor, a neoplasm not previously described as causing obstruction in the pancreas.

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In the plasma, lysophosphatidylcholine (LPC) is formed by the action of lecithin-cholesterol acyltransferase (LCAT) when a fatty acid is removed from plasma phosphatidylcholine (PC) and transferred to cholesterol. To determine whether plasma LPC might also be generated by the hydrolysis of hepatic PC, we assessed phospholipid production by the isolated perfused rat liver. Bile duct-cannulated livers were perfused with bile salt and a recirculating, lipid-free medium containing albumin. We found that LPC accumulated in the perfusate to a greater extent than any other phospholipid, exceeding the accumulation of PC (the second most prevalent phospholipid) twofold. We further found that perfusate LPC was not formed by hydrolysis of PC in the perfusate and was not dependent on the presence of infused bile salt. LPC that accumulated in the perfusate was highly unsaturated and markedly dissimilar to the more saturated LPC that results from the activity of LCAT. Results thus indicate that the isolated liver directly secretes LPC, which is presumably generated from hydrolysis of hepatic PC. Because plasma LPC is to a great extent unsaturated in the live rat, these findings suggest that direct hepatic secretion is a quantitatively important source of plasma LPC.

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A study was conducted to determine the prevalence and incidence of stress-associated illnesses and to identify possible sources of stress among students enrolled in the M.D.-Ph.D. program of a midwestern university. Specially constructed questionnaires were completed by 45 M.D.-Ph.D. students, 334 M.D. students, and 42 Ph.D. students at this university. The information obtained from the M.D.-Ph.D. students was compared with the responses of the M.D. students and the Ph.D. students. Male M.D.-Ph.D. students had a significantly higher incidence of hypertension, colitis, and asthma, while female M.D.-Ph.D. students reported a higher usage of antacids and occurrence of gastritis or ulcers during the time that they were enrolled in their programs. M.D.-Ph.D. students indicated that the fear of flunking out of school and the grading system were more stressful than did the M.D. students. Additionally, relationship with the graduate adviser and the graduate committee was more stressful to M.D.-Ph.D. students than to Ph.D. students.

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In serial studies of hepatic function in rats after 70% partial hepatectomy, quantitative changes were found in several of the serum components used clinically to assess liver status. The activities of the following enzymes were found to increase: gamma-glutamyl transpeptidase and lactic dehydrogenase were maximal 6 h postoperatively, while glutamic oxaloacetic transaminase and alkaline phosphatase reached peak values at 24 and 48 h respectively. Albumin levels were found to be relatively constant during the study; however, total protein concentration was lowest 6--12 h postoperatively, paralleling a decrease in globulin concentration. Bilirubin levels were elevated to 4x normal within 12 h after surgery. After partial hepatectomy calcium and phosphorus concentrations were significantly decreased at 24 and 12 h respectively. With the exception of alkaline phosphatase, the activities of all serum components measured returned to normal levels by 1 week after surgery; the alkaline phosphatase concentration continued to be elevated 2 weeks postoperatively.

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