Non-oxidative metabolism of ethanol by rat pancreatic acini.

BACKGROUND: The pathogenesis of alcoholic pancreatitis may involve the metabolism of ethanol (via oxidative and non-oxidative pathways) within the pancreas. The aims of this study were to determine the rate of non-oxidative metabolism in isolated rat pancreatic acini and to compare this to the rate of ethanol oxidation. METHODS: Pancreatic acini were isolated from male Sprague-Dawley rats and incubated with (14)C-ethanol. Radiolabelled fatty acid ethyl esters (non-oxidative metabolites) were isolated from lipid extracts by thin-layer chromatography. Radiolabelled acetate (oxidative metabolite) was isolated from the incubation medium by ion-exchange chromatography. RESULTS: Non-oxidative metabolism by isolated pancreatic acini was demonstrated. At 50 and 100 mmol/l ethanol, fatty acid ethyl ester concentrations were 49.6 +/- 13.3 and 199 +/- 93 micromol/l, respectively. These levels have previously been shown to result in tissue injury. Non-oxidative metabolism was increased 9-fold by addition of oleic acid and inhibited by the lipase inhibitor, tetrahydrolipstatin, by 91.05 +/- 1.99%. The rate of oxidative metabolism was 21-fold higher than that of non-oxidative metabolism. CONCLUSIONS: Intact pancreatic cells metabolize ethanol by the non-oxidative pathway, generating fatty acid ethyl esters at a rate sufficient to cause pancreatic damage. Oxidative metabolism of ethanol occurs at a much higher rate and may also play a role in pancreatitis.     

Dose- and time-dependent changes in plasma catecholamines in response to endotoxin in conscious rats

Time- and dose-dependent changes in plasma catecholamines, heart rate, and blood pressure were studied in response to sublethal doses of intravenous (i.v.) bacterial endotoxin in conscious male rats. Hypotension occurred with high endotoxin (1,000 micrograms/kg), whereas hypertension occurred in the low-dose group (10 micrograms/kg). All groups had significant tachycardia, which was dose and time dependent, but heart rate was unchanged for the first 2 hr in the low-dose groups (100 and 10 micrograms/kg). Plasma levels of norepinephrine (NE) and epinephrine (E) increased with both dose and time and there was significant interaction of dose and time effects. NE levels increased maximally at 0.5 hr following the highest dose of endotoxin and remained elevated during the protocol. Plasma E levels were maximal at 0.5 hr in the high-dose group, but then declined while remaining significantly higher than the 10 and 100 micrograms/kg endotoxin-treated groups for the duration of the protocol. Peak E levels in the 100 and 10 micrograms/kg group occurred at 3.0 hr and then decreased at the 6.0 hr time. Significant increases in plasma catecholamines and heart rate with endotoxin in the absence of significant hypotension present the possibility that factors other than blood pressure may be mediating efferent sympathetic outflow in endotoxicosis.     

Efficacy and tolerability of antibiotics in patients undergoing H. pylori eradication

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) infection is one of the most common gastrointestinal diseases. An increasing number of people undergo different treatment options. Unfortunately, H. pylori therapy may be troublesome for drug side effects and inefficacious for resistance to antibiotics. METHODOLOGY: One hundred and ninety-three (193) H. pylori-positive patients were randomly assigned to one of the following 7-day treatments: Group A (N = 64): amoxicillin, clarithromycin and rabeprazole; Group B (N = 64): tinidazole, clarithromycin and ranitidine bismuth citrate; Group C (N = 65): tinidazole, clarithromycin and rabeprazole Eradication was assessed by 13C-Urea Breath Test 6-8 weeks after the end of the therapy. Not-eradicated patients underwent a second cycle with tinidazole, tetracycline, bismuth and rabeprazole. All patients were asked to complete a validated questionnaire regarding presence and intensity of drug side effects. RESULTS: One hundred and eighty-eight out of the 193 H. pylori-positive patients (96%) completed therapy. No significant difference in eradication rates was observed among the three groups both in intention to treat analysis and in per protocol analysis. No significant difference in incidence of side effects occurred among groups after the first-line regimens: 48% in group A, 44% in group B and 46% in group C. Twenty-two out of the 193 enrolled subjects (11%) were not eradicated after the first-line therapy. Among them, 86% were successfully eradicated by the tinidazole, tetracycline, bismuth and rabeprazole therapy. Moreover, during quadruple therapy, a higher prevalence and intensity of side effects than in each one of the groups submitted to the first-line triple therapy was observed. CONCLUSIONS: This study shows that triple rabeprazole-based eradicating regimens are effective and safe. Incidence of side effects seems low and similar in different three-drug regimens used. Quadruple therapy, which appear highly efficacious as a second line therapy, is associated with a significantly higher incidence of side effects when compared to first-line treatment.     

Long-term follow-up after endoscopic biliary stent placement for bile duct strictures from laparoscopic cholecystectomy

BACKGROUND/AIMS: The outcome of endoscopic biliary stent insertion for postoperative bile duct stenosis was retrospectively evaluated. METHODOLOGY: Fifty-seven patients with biliary stenosis from laparoscopic cholecystectomy were included from February 1992 to January 2000. One to three stents were inserted for an average of 12.4 months, with stent exchange every 3 months to avoid cholangitis caused by clogging. RESULTS: Successful stent insertion was achieved in 43/57 (75.4%) patients. Stent insertion failed in 10 patients with complete and in 4 patients with incomplete biliary obstruction. Early complications occurred in 4 patients. Late complications occurred in 5/43 patients. Five patients experienced recurrence of stenosis. CONCLUSIONS: Endoscopic treatment should be the initial management of choice for postoperative bile duct stenosis.     

Exploration of the early insulin response by two small successive loads of I.V. glucose in normal and obese subjects

Summary Two 5 g glucose loads at 1-h interval were given to healthy controls and obese subjects with slightly altered or normal OGTT in order to explore the capacity of restoration of the ‘rapid insulin response’ to i.v. glucose. In the normal subjects, the two successive loads gave rise to identical responses as far as maximum increase (Δ_max), average increase at 2–5 min (Δ_{2–5 min}), area of increase 0–15 min (Δ_{0–15 min}) for both glucose and IRI, were concerned. Obese subjects could be divided on the basis of their insulin response to the first load into normal responders (group I) and high-responders (group II). In group I obese subjects, the responses to the second load were identical to those to the first. In group II obese subjects Δ_max, Δ_{2–5 min} and Δ_{0–15 min} of the insulin response to the second load were reduced as compared to the first.     

Emergency Department Visits after Kidney Transplantation

Background and objectives

In 2011, there were approximately 131 million visits to an emergency department in the United States. Emergency department visits have increased over time, far outpacing growth of the general population. There is a paucity of data evaluating emergency department visits among kidney transplant recipients. We sought to evaluate the incidence and risk factors for emergency department visits after initial hospital discharge after transplantation in the United States.

Design, setting, participants, & measurements

We identified 10,533 kidney transplant recipients from California, New York, and Florida between 2009 and 2012 using the State Inpatient and Emergency Department Databases included in the Healthcare Cost and Utilization Project. We used multivariable Poisson and Cox proportional hazard models to evaluate adjusted incidence rates and time to emergency department visits after transplantation.

Results

There were 17,575 emergency department visits over 13,845 follow-up years (overall rate =126.9/100 patient-years; 95% confidence interval, 125.1 to 128.8). The cumulative incidences of emergency department visits at 1, 12, and 24 months were 12%, 40%, and 57%, respectively, with median time =19 months; 48% of emergency department visits led to hospital admission. Risk factors for higher emergency department rates included younger age, women, black and Hispanic race/ethnicity, public insurance, depression, diabetes, peripheral vascular disease, and emergency department use before transplant. There was wide variation in emergency department visits by individual transplant center (10th percentile =70.0/100 patient-years; median =124.6/100 patient-years; and 90th percentile =187.4/100 patient-years).

Conclusions

The majority of kidney transplant recipients will visit an emergency department in the first 2 years post-transplantation, with significant variation by patient characteristics and individual centers. As such, coordination of care through the emergency department is a critical component of post-transplant management, and specific acumen of transplant-related care is needed among emergency department providers. Additional research assessing best processes of care for post-transplant management and health care expenditures and outcomes associated with emergency department visits for transplant recipients are warranted.