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M L Shiffman

Publications and source records attributed to M L Shiffman.

At least 73 records · Page 4Linked to original sources
PubMed1995

A multicenter, placebo-controlled, randomized, double-blind, prospective trial of prophylactic ursodiol for the prevention of gallstone formation following gastric-bypass-induced rapid weight loss.

BACKGROUND: Previous studies have documented a high incidence of gallstone formation following gastric-bypass (GBP)-induced rapid weight loss in morbidly obese patients. This study was designed to determine if a 6-month regimen of prophylactic ursodiol might prevent the development of gallstones. METHODS: A multicenter, randomized, double-blind, prospective trial evaluated 3 oral doses of ursodiol: 300, 600, and 1,200 mg versus placebo beginning within 10 days after surgery and continuing for 6 months or until gallstone development, for patients with a body mass index (BMI) > or = 40 kg/m2. All patients had normal intraoperative gallbladder sonography. Transabdominal sonography was obtained at 2, 4, and 6 months following surgery, or until gallstone formation. RESULTS: Of 233 patients with at least one postoperative sonogram, 56 were randomized to placebo, 53 to 300 mg ursodiol, 61 to 600 mg ursodiol, and 63 to 1,200 mg ursodiol. Preoperative age, sex, race, weight, BMI, and postoperative weight loss were not significantly different between groups. Gallstone formation occurred at 6 months in 32%, 13%, 2%, and 6% of the patients on the respective doses. Gallstones were significantly (P < 0.001) less frequent with ursodiol 600 and 1,200 mg than with placebo. CONCLUSION: A daily dose of 600 mg ursodiol is effective prophylaxis for gallstone formation following GBP-induced rapid weight loss.

Adolescent↗
PubMed1995

The role of transjugular intrahepatic portosystemic shunt for treatment of portal hypertension and its complications: a conference sponsored by the National Digestive Diseases Advisory Board.

TIPS is a new and exciting modality for treatment of portal hypertension and its complications. Indications for TIPS remain to be better defined in terms of efficacy and cost-benefit in relationship to other established modes of therapy of portal hypertension. Prospective, randomized controlled trials are needed for these comparisons. Until the role of TIPS in the routine management of the complications of portal hypertension is better defined, TIPS should be used only in situations in which conventional medical and endoscopic therapies have failed.

Humans↗
PubMed1994

Biochemical and histologic evaluation of recurrent hepatitis C following orthotopic liver transplantation.

It is well recognized that hepatitis recurs in virtually all patients who undergo orthotopic liver transplantation for cirrhosis secondary to chronic hepatitis C (HCV). The present report describes the biochemical and histologic findings of recurrent hepatitis in 25 such patients. One patient was found to have hepatocellular carcinoma at the time of OLT and was excluded from further analysis. All post-OLT laboratory values were reviewed. Liver biopsies were performed on protocol 6, 12, 24, and 36 months following OLT. Additional biopsies were performed as necessary to evaluate abnormalities in serum liver chemistries. A total of 104 biopsies was obtained; hepatitis consistent with recurrent HCV was present in 68 (65%). Other biopsy findings included cytomegalovirus hepatitis; acute, chronic, or resolving rejection; cholestasis with or without an underlying hepatitis; steatosis, and centrilobular necrosis. Histologic hepatitis appeared in all patients within 12 months following OLT. Despite these histologic findings, serum ALT was normal for prolonged periods in over 50% of such patients. In all cases this hepatitis was mild and did not progress over a mean follow-up of 22 months (maximum 44 months), as judged by Knodell histologic activity score (mean score: 4.0 +/- 0.3). Five patients developed cholestatic jaundice, far out of proportion to the degree of histologic hepatitis. In 2 patients this was secondary to chronic rejection. The other 3 patients had drug-induced cholestasis that resolved after various medications were discontinued. HCV did not contribute to graft dysfunction in any of the 24 patients. To date, our data suggest that post-OLT hepatitis in patients with preexisting HCV is a relatively benign process. Severe cholestatic jaundice in such patients is not secondary to HCV, and should stimulate a search for other possible causes of graft dysfunction. The long-term consequences of recurrent HCV following hepatic transplantation remain to be determined.

Adult↗
PubMed1994

Portosystemic encephalopathy after transjugular intrahepatic portosystemic shunt: results of a prospective controlled study.

Portosystemic encephalopathy is a common complication of surgical portacaval shunts. Recently, transjugular intrahepatic portosystemic shunts have been proposed to produce portal decompression in a manner analogous to a side-to-side portacaval shunt, but with less morbidity. The incidence and clinical spectrum of portosystemic encephalopathy after transjugular intrahepatic portosystemic shunts, however, had not been previously prospectively defined. We therefore prospectively studied portosystemic encephalopathy in 30 patients undergoing transjugular intrahepatic portosystemic shunts and compared these findings with 25 patients concurrently undergoing sclerotherapy (controls). At entry, both study groups were comparable. Portosystemic encephalopathy was assessed by examining and grading mental status, asterixis, plasma ammonia and trail making tests. The portosystemic encephalopathy index was calculated from these parameters. Nine of 30 patients with transjugular intrahepatic portosystemic shunts experienced 24 episodes of acute portosystemic encephalopathy during follow-up; 6 of 9 had a history of portosystemic encephalopathy before transjugular intrahepatic portosystemic shunts and 5 of these 6 patients had Child C cirrhosis. Mental status and asterixis scores as well as portosystemic encephalopathy index worsened significantly in the first month after transjugular intrahepatic portosystemic shunts but showed some improvement thereafter. Increasing age, a medical history of portosystemic encephalopathy and trail scores for part B greater than 100 sec were predictors of portosystemic encephalopathy after transjugular intrahepatic portosystemic shunts. Portosystemic encephalopathy could be managed medically in all but one patient who underwent liver transplant. In contrast, there were no significant changes in mental status, asterixis, ammonia or trail scores over time in sclerotherapy controls. Only six episodes of encephalopathy occurred in endoscopic sclerotherapy patients over the duration of the study. Thus, overall risk of portosystemic encephalopathy after transjugular intrahepatic portosystemic shunts was higher than during sclerotherapy.

Esophageal and Gastric Varices↗
PubMed1994

Oxaprozin-induced fulminant hepatitis.

OBJECTIVE: To report oxaprozin-induced fulminant hepatic failure. CASE SUMMARY: A 56-year-old woman was admitted with fulminant hepatic failure. Work-up for potential etiologies was negative except for the use of oxaprozin for the preceding two months. Results of premortem liver biopsy were consistent with drug-induced hepatic injury similar to that previously reported with diclofenac. DISCUSSION: Although the literature describes elevation in hepatic transaminase concentrations associated with oxaprozin, fulminant hepatic failure has not been described previously. CONCLUSIONS: Elevations in hepatic transaminase concentrations and now fulminant hepatic failure have been shown to occur with oxaprozin, as previously seen with other nonsteroidal antiinflammatory drugs (NSAIDs). Transaminitis is a known adverse effect of NSAID use, but is usually mild and reversible with discontinuation of drug. Transaminitis may be more likely to occur in the elderly, in patients receiving concurrent potentially hepatotoxic medications, and possibly with the newer long-acting NSAIDs. The existence of fulminant hepatitis, although rare, supports the need for monitoring liver function enzymes during NSAID therapy.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1994

Induction with OKT3 and prostaglandin E1 in liver transplantation.

Forty-six consecutive adult patients underwent 51 orthotopic liver transplants in a prospective study to evaluate sequential induction with ORTHOCLONE OKT3 (muromonab-CD3), prostaglandin E1, cyclosporine, azathioprine, and methylprednisolone. Infection prophylaxis included preoperative bowel preparation and ganciclovir if cytomegalovirus was diagnosed in either donor or recipient. All rejection episodes were documented by liver biopsy before treatment. Seventy-four percent of patients evaluable beyond 1 year have had no rejection episodes. The retransplant rate was 10%, with a 4% primary nonfunction rate. There was no rejection of grafts that could not be retreated with OKT3. Forty-two percent (5 of 12) of rejection episodes responded to steroid recycling alone. The infection rates for all patients at 1 year were 54% bacterial, 17% fungal, and 22% viral. Three septic deaths were attributed to overimmunosuppression. Two-year patient and graft survival rates were 80% and 72%, respectively. This OKT3 induction protocol results in limited rejection episodes without increasing infections, yielding an acceptably low rate of graft loss.

Adult↗
PubMed1994

Hepatic lidocaine metabolism and liver histology in patients with chronic hepatitis and cirrhosis.

Recent advances in the medical and surgical treatment of chronic hepatitis and cirrhosis have made it increasingly important to develop noninvasive tests of liver function. Our study has evaluated the hepatic conversion of lidocaine to its primary metabolite monoethylglycinexylodide and compared this with liver histological findings in 225 patients with chronic hepatitis (161 with hepatitis C, 23 with hepatitis B, 21 with autoimmune hepatitis and 20 with cryptogenic hepatitis). One hundred seven (47.7%) patients had cirrhosis at the time of evaluation. A decline in monoethylglycinexylodide production was observed with worsening liver histological conditions from a mean of 81.5 +/- 7.0 ng/ml in patients with chronic persistent hepatitis to 61.2 +/- 5.5 ng/ml for chronic active hepatitis and 20.9 +/- 1.5 ng/ml in patients with cirrhosis (p < 0.05). A further stepwise decline in monoethylglycine xylodide production was observed with worsening Child class: from 25.5 +/- 2.2 ng/ml for class A patients to 8.9 +/- 1.4 ng/ml for patients with Child class C disease (p < 0.05). All patients with monoethylglycinexylodide production less than 20 ng/ml had cirrhosis confirmed on histological examination. In contrast, no relationship was observed between liver histological status and serum transaminases (AST or ALT), bilirubin, albumin and prothrombin time. Thirty-five patients underwent repeat histological evaluation and monoethylglycinexylodide testing after receiving at least 6 mo treatment for chronic hepatitis (interferon for hepatitis B and C and corticosteroids for autoimmune hepatitis). The change in monoethylglycinexylodide production observed in these patients was a linear function of the change in Knodell histological index (r = 0.73, p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Gallbladder mucin, arachidonic acid, and bile lipids in patients who develop gallstones during weight reduction.

BACKGROUND: Arachidonic acid (AA) and hydrophobic bile salts (BS) stimulate gallbladder mucin (GBM) secretion, which is thought to be an essential step in gallstone pathogenesis. The present study was performed to evaluate the relationship between AA, BS, and GBM in patients who develop gallstones following weight reduction. METHODS: Eleven patients who underwent gastric bypass, developed symptomatic gallstones, and then underwent cholecystectomy were evaluated. Gallbladder bile was obtained for analysis during each procedure. Matched patients who did not develop gallstones following gastric bypass served as controls. RESULTS: GBM increased in every patient who developed stones (mean increase: 5000%). The largest increase was observed soon after gastric bypass, and this declined curvilinearly with time. Gallbladder bile cholesterol was initially elevated but then rapidly declined before increasing back to pregastric bypass levels after weight loss was complete. No significant changes in phosphatidylcholine molecular species (including AA) or BS composition were observed following weight reduction. Concentrations of cholesterol, phospholipids, and changes in [AA] over time were each a linear function of [BS]. No relationship between GBM and any of these bile constituents was apparent. CONCLUSIONS: These observations strongly suggest that increases in GBM, which occur with gallstone formation in humans, are not the result of alterations in biliary AA or BS composition.

Adult↗
PubMed1993

Hepatic lidocaine metabolism and complications of cirrhosis. Implications for assessing patient priority for hepatic transplantation.

The number of patients awaiting hepatic transplantation continues to exceed organ donation. As a result, many liver transplant candidates will develop life-threatening complications of their liver disease and not survive the pretransplant waiting period. Recent studies have demonstrated that hepatic lidocaine metabolism into monoethylglycinexylidide (MEG-X) can predict pretransplant survival. The present study was performed to determine if MEG-X could also predict pretransplant complications and thereby be useful in stratifying persons being evaluated for hepatic transplantation. A total of 57 patients with biopsy-proven cirrhosis underwent MEG-X testing. Of 57 patients, 30 (53%) developed life-threatening complications of their liver disease--i.e., variceal bleeding, grade II hepatic encephalopathy or worse, and spontaneous bacterial peritonitis. MEG-X values were greater in persons without complications of liver disease than in persons with complications (25.7 +/- 2.9 versus 14.7 +/- 1.4 ng/ml, respectively). No patients with MEG-X greater than 30 ng/ml developed a major complication. No significant difference in any of the standard liver function tests existed between persons who developed complications and patients who did not. In this group of 57 patients, 4 (7%) died from complications of cirrhosis. Mean MEG-X for patients who died (5.5 +/- 1.6 ng/ml) was significantly less (P < 0.05) than observed for other patient groups. All patients who died had MEG-X values below 10 ng/ml. This suggests that MEG-X testing could be an extremely useful test in the evaluation of patients for hepatic transplantation by identifying persons at increased risk for developing complications of chronic liver disease.

Adult↗
PubMed1993

Complications of transjugular intrahepatic portosystemic shunt: a comprehensive review.

It is generally accepted that the transjugular intrahepatic portosystemic shunt (TIPS) procedure has lower morbidity and mortality rates than those of surgical shunting. Nevertheless, complications occur. The authors have reviewed their experience and that of other institutions in compiling an extensive list of complications. Complications are categorized according to those related to transhepatic needle puncture, transvenous access to the portal vein, portal venous cannulation, the stent, the puncture site, portosystemic shunting, and contrast material. Excluding hepatic encephalopathy and delayed stenosis or occlusion of the shunt, an overall complication rate of less than 10% can be expected for TIPS. The prevalence of aggravated or new cases of encephalopathy is 5%-35%, and over the long term, up to 75% of shunts may undergo stenosis or occlusion. The direct procedural mortality rate is less than 2%, and the 30-day mortality rate ranges from 4% to 45%, depending on several factors. The role to which TIPS is relegated will be influenced by the long-term success rate in the prevention of recurrent variceal hemorrhage.

Catheterization, Peripheral↗
PubMed1993

Cultured human gallbladder epithelia. Methods and partial characterization of a carcinoma-derived model.

BACKGROUND: Gallstone disease remains a leading cause of morbidity and mortality in humans. Despite extensive research into the physiology of the gallbladder, little is known about mucosal events that precede and contribute to stone formation. Here, we describe and partially characterize a cultured epithelial model of human gallbladder mucosa. EXPERIMENTAL DESIGN: Cells originally obtained from a well-differentiated gallbladder mucosal carcinoma were cultured in modified Eagle's minimum media (supplemented with fetal calf serum and antibiotics) on polycarbonate supporting matrices. RESULTS: Cell cultures were observed to come to confluence with 6 to 9 days. Light and transmission electron microscopy demonstrated the resultant epithelia to be predominantly one cell thick, to be polar in orientation, and to have apical villi. Epithelia exhibited cytokeratin markers consistent with their epithelia origin, functionally acidified the mucosal bathing solutions, and secreted mucin. Further experiments demonstrated transepithelial potential differences, mucosal-to-serosal transfer of sodium which could be inhibited with amiloride and 4-acetamido-4'-isothiocyanatostilbene-2-2'-disulfonic acid, and paracellular movement of neutral molecular probes inversely related to size. CONCLUSIONS: This culture model of human gallbladder mucosal carcinoma cells exhibits parameters consistent with native gallbladder and may offer a convenient new research tool for the study of the pathophysiology of gallstone formation.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1993

Gallstones in patients with morbid obesity. Relationship to body weight, weight loss and gallbladder bile cholesterol solubility.

Gallstones are common in obesity, and in individuals undergoing weight reduction. However, the relationships between body weight, weight reduction, gallbladder bile composition and gallstone formation are not well understood. The present studies were conducted on a cohort of 230 morbidly obese individuals presenting for bariatric surgery. Mean body weight ranged from 90-235.4 kg (mean: 136.2 kg). Body mass index (BMI) ranged from 35.4-94.7 kg/m2. Thirty-two patients (14%) had undergone prior cholecystectomy and 48 (21%) were found to have gallstones by intraoperative ultrasonography. No significant relationship was observed between gallstone prevalence and body weight. Following bariatric surgery weight loss averaged 1.57 kg/week over six months. Absolute weight loss ranged from 13.6-81.3 kg. Symptomatic gallstones requiring cholecystectomy developed in 15/150 patients (10%) over two years of follow-up. In contrast, ultrasonography detected asymptomatic gallstones in 34/92 patients (37%) six months following bariatric surgery. No relationship existed between the amount of weight lost and gallstone formation. Gallbladder bile cholesterol solubility remained constant throughout the entire weight range present in this population. No significant difference in cholesterol solubility was present between persons presenting for bariatric surgery and patients who developed symptomatic gallstones and underwent cholecystectomy following weight reduction. We conclude that gallstones are common in patients with severe obesity both before and following bariatric surgery. However, weight loss per se does not appear to be the major determinant of gallstone formation in persons who weigh in excess of 100 kg.

Adult↗
PubMed1992

Changes in gallbladder bile composition following gallstone formation and weight reduction.

Changes in gallbladder bile composition that occurred in patients who developed gallstones during weight reduction were evaluated. Bile was sampled directly from the gallbladder in 11 morbidly obese patients with no gallstones at the time of gastric bypass surgery and after gallstones had formed at cholecystectomy. Bile salt concentration ([BS]) increased significantly from a mean of 82.7-157.7 mmol/L (P less than 0.05). The concentration of cholesterol in gallbladder bile increased slightly and cholesterol saturation declined slightly with weight reduction and gallstone formation. Gallbladder mucin concentration increased 18-fold from a mean of 62 to 1110 micrograms/mL (P less than 0.001). Both free [Ca2+] and total calcium [Ca] increased 40% from mean values of 1.12 and 5.05 mmol/L at gastric bypass to 1.86 and 8.60 mmol/L after gallstone formation (P less than 0.05). The increase in [Ca2+] observed after gallstone formation was much greater than anticipated from changes in [BS] alone. This excess [Ca2+] in gallbladder bile increased curvilinearly with increasing mucin concentration. These results show that both gallbladder mucin and [Ca2+] increase with gallstone formation in humans and that mucin may modulate [Ca2+] in gallbladder bile.

Adult↗