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Biomedical subjects

M L Shiffman

Publications and source records attributed to M L Shiffman.

At least 55 records · Page 3Linked to original sources
PubMed1998

Human gallbladder mucosal function: effects on intraluminal fluid and lipid composition in health and disease.

Gallbladder mucosal absorption of fluid during fasting is a well-known process. Indirect in vivo and recent in vitro evidence for physiologically relevant gallbladder absorption of cholesterol and phospholipids from bile has been observed in humans. The present study explored and compared by indirect means the relative efficiences of human gallbladder mucosal absorption of fluid and lipids in health and disease. Biliary lipids and pigment content were measured in fasting gallbladder bile samples obtained from gallstone-free controls and from four study groups: multiple and solitary cholesterol gallstone patients, and morbidly obese subjects with and without gallstones. Bile salts and pigment content were significantly greater in gallstone-free controls than in all other disease study groups. This was interpreted as evidence of more effective gallbladder mucosal fluid absorption in nonobese gallstone-free controls compared to that in all other groups. Correlation plot analyses of biliary lipids showed lower concentrations of phospholipids than expected from the index bile salt concentrations. The same was found for cholesterol concentrations but only in supersaturated samples. These findings were much more pronounced in gallstone free-controls and were accordingly interpreted as evidence of more efficient gallbladder absorption of both phospholipids and cholesterol in controls compared with that found in each of the disease study groups. Moreover, impaired gallbladder mucosal function, while invariably associated with cholesterol gallstone disease, was not found to be a necessary consequence of the physical presence of stones. It is concluded that efficient gallbladder mucosal absorption of both fluid and apolar lipids from bile is a normal physiological process that is often seriously impaired in the presence of either cholesterol gallstone disease or at least one of its precursor forms.

Absorption↗
PubMed1997

Transjugular intrahepatic portosystemic shunts compared with endoscopic sclerotherapy for the prevention of recurrent variceal hemorrhage. A randomized, controlled trial.

BACKGROUND: Transjugular intrahepatic portosystemic shunts (TIPS) have widened the use of portal decompression as therapy for variceal hemorrhage. However, no controlled studies have examined the efficacy of TIPS compared with that of other treatments. OBJECTIVE: To compare the efficacy and safety of TIPS with those of endoscopic sclerotherapy for the prevention of recurrent variceal hemorrhage. DESIGN: Randomized, controlled trial. SETTING: Tertiary-care academic medical center. PATIENTS: 100 patients with cirrhosis were evaluated a mean of approximately 10 days after an episode of acute variceal bleeding; 20 patients were excluded because of portal venous thrombosis (n = 6), hepatoma (n = 3), florid alcoholic hepatitis (n = 6), and refusal to give consent (n = 5). INTERVENTIONS: TIPS (n = 41) or sclerotherapy (n = 39). The latter was performed by freehand injections of 5% Na morrhuate at 2- to 3-week intervals. Recurrent variceal hemorrhage was managed by sclerotherapy followed by angiographic assessment of TIPS and dilatation of the stents (TIPS group) or crossover to TIPS (sclerotherapy group). MEASUREMENTS: Rebleeding and survival were the primary end points. Complications and rates of rehospitalization were secondary end points. RESULTS: During a mean follow-up of approximately 1000 days, recurrent gastrointestinal bleeding resulted from variceal hemorrhage (9 patients in the TIPS group and 8 in the sclerotherapy group), portal gastropathy (1 patient in each group), and gastric lipoma (0 and 1 patients, respectively). A higher mortality rate was seen with TIPS (P = 0.03). Death resulted from variceal bleeding (5 patients in the TIPS group and 3 in the sclerotherapy group), sepsis (3 and 2 patients, respectively), liver failure (2 patients in each group), hepatoma (1 and 0 patients, respectively), and hemoperitoneum (1 and 0 patients, respectively). Encephalopathy was the most common complication in the TIPS group (n = 12), and pain developing after sclerotherapy was the most common in the sclerotherapy group (n = 10). The two groups had similar rates of rehospitalization. CONCLUSIONS: Endoscopic sclerotherapy and TIPS are equivalent with respect to rebleeding developing over the long term. However, sclerotherapy may be superior to TIPS with respect to survival.

Adult↗
PubMed1997

Relationship between biochemical, virological, and histological response during interferon treatment of chronic hepatitis C.

The present study was conducted to evaluate the relationship between biochemical, virological, and histological response during the course of interferon therapy. Ninety consecutive patients with well-documented chronic hepatitis C virus (HCV) were treated with 5 MU of interferon alfa-2b three times weekly for 6 months. Liver biopsy was performed, and serum HCV RNA titer was measured before and at the completion of interferon treatment. Normalization of serum alanine transaminase (ALT) concentration (biochemical response) was observed in 50% of patients. In these patients, Knodell score declined significantly from 9.6 +/- 0.5 to 5.0 +/- 0.5 (P < .01), and 75% became HCV RNA negative. The remaining patients (50%) were biochemical nonresponders; mean Knodell score declined from 9.6 +/- 0.5 to 7.7 +/- 0.5 (P < .01), and 11% became HCV RNA negative. For both biochemical responders and nonresponders, the decline in Knodell score was confined to the components of hepatic inflammation (piecemeal necrosis + lobular + portal inflammation); no change in fibrosis was observed. Hepatic inflammation declined by 5 points or more in 69% of biochemical responders and 48% of biochemical nonresponders, and by at least 50% from pretreatment values in 74% and 38% of biochemical responders and biochemical nonresponders, respectively. For all patients (both biochemical responders and nonresponders) who remained viremic at the conclusion of interferon therapy, the reduction in hepatic inflammation was a linear function of the decline in HCV RNA titer. We conclude that more than one third of patients who had no biochemical response after 6 months of interferon therapy achieved a similar improvement in hepatic histology as was observed in patients with biochemical response. This improvement in hepatic histology appeared to correlate with a reduction in HCV RNA titer, especially in patients who remained viremic.

Adult↗
PubMed1997

Minimal criteria for placement of adults on the liver transplant waiting list: a report of a national conference organized by the American Society of Transplant Physicians and the American Association for the Study of Liver Diseases.

This report summarizes a recent meeting cosponsored by the American Society of Transplant Physicians and the American Association for the Study of Liver Diseases to formulate minimal criteria by which patients with severe liver disease will be placed on the waiting list for liver transplantation. The participants agreed that only patients in immediate need of liver transplantation should be placed on the waiting list. Patients should not be placed in anticipation of some future need for such therapy. It was agreed that minimal criteria could assist but not replace the clinical judgment of the transplant professionals at individual centers. The criteria will be summarized below for adult patients with acute or chronic liver disease. The most important non-disease-specific criterion for placement on the transplant waiting list was an estimated 90% chance of surviving 1 year. This translated into a Child-Pugh score of > or = 7 for patients with cirrhosis which places the patient in Child-Pugh class B or C. Cirrhotic patients who have experienced gastrointestinal bleeding caused by portal hypertension or a single episode of spontaneous bacterial peritonitis would meet the minimal criteria irrespective of their Child-Pugh score. There were disease-specific criteria also. These include a sole minimal criterion for patients with fulminant hepatic failure regardless of etiology of the onset of stage 2 hepatic encephalopathy. A requirement for 6 months abstinence from alcohol before placement on the transplant waiting list was considered appropriate for most patients with alcoholic liver disease. Exceptional cases could get access to the waiting list through a regional review process. Chronic cholestatic diseases present difficulties because of a different natural history than that of chronic hepatocellular diseases. The use of specific risk scores for primary biliary cirrhosis and primary sclerosing cholangitis will likely replace Childs-Pugh classification as the scoring systems become refined. Minimal criteria for any patient with a primary hepatocellular cancer would admit any patient with a tumor confined to the liver irrespective of size or number of tumors, after careful investigation had failed to show spread to lymph nodes, the portal vein, or distant organs. Unusual or rare indications for liver transplantation, including Budd-Chiari syndrome, Wilson's disease, and other hereditary disorders, were also discussed. Finally, it was agreed that there should be no absolute contraindications to placement of patients on the liver transplant waiting list. These criteria should be open to regular review to accommodate advances in the field.

Adult↗
PubMed1997

An atypical presentation for primary sclerosing cholangitis.

We describe the clinical course of a group of patients with primary sclerosing cholangitis who at presentation were diagnosed to have autoimmune hepatitis. The history of one such patient is described in detail. We also compare this atypical sclerosing cholangitis (group I) to typical sclerosing cholangitis (group II) and to autoimmune hepatitis with (group III) and without (group IV) cholestasis. At presentation, mean AST in groups I and III was similar and significantly higher than in group II (P < 0.05). Mean ALP was higher in sclerosing cholangitis than in autoimmune hepatitis but not significantly so. Triaditis was present in all patients in groups I, III, and IV. Piecemeal necrosis and multilobular collapse/fibrosis were equally frequent in groups I, III, and IV. Only the response to corticosteroids helped differentiate among groups. Groups III and IV responded by normalizing AST. In group I, AST improved, but never became normal. As ALP became disproportionately abnormal (ALP-predominant pattern), cholangiography was performed, and the diagnosis of primary sclerosing cholangitis was made in all group I patients. We recommend that cholangiography be performed early in patients with suspected autoimmune hepatitis who partially respond to corticosteroids and develop an ALP-predominant pattern.

Adrenal Cortex Hormones↗
PubMed1997

The natural history of portal hypertension after transjugular intrahepatic portosystemic shunts.

BACKGROUND & AIMS: The effects of transjugular intrahepatic portosystemic shunt (TIPS) on portal hemodynamics, esophageal and gastric varices, and hepatic function have not been fully defined. The aim of this study was to define prospectively the effects of TIPS on portal pressures and flow, variceal resolution, and hepatic function. METHODS: Pressure and flow measurements were made by angiography and Doppler sonography, respectively. Varices were assessed by endoscopy and angiography. Liver functions were evaluated by a battery of tests. RESULTS: In 100 consecutive subjects, mean portosystemic gradient decreased from 24 to 11 mm Hg (means) (P < 0.001) after TIPS. Recurrent portal hypertension caused by stent thrombosis (n = 5), stent retraction (n = 2), and stent stenosis (n = 51) occurred at 6 months but, by year 5, was not present in survivors (n = 0 of 8). Fundic gastric varices failed to resolve in 6 of 12 cases. Systemic venous pressures of >15 mm Hg, stent dysfunction, and continued alcoholism were risk factors for recurrent hemorrhage. Angiography was superior to endoscopy, which was superior to Doppler sonography for detection of recurrent portal hypertension. Progressive liver failure occurred in 8 patients. CONCLUSIONS: Recurrent portal hypertension caused by stent stenosis occurs commonly in the first 2 years after TIPS. Fundic gastric varices often fail to disappear after TIPS. The effects of TIPS on liver function are unpredictable.

Adult↗
PubMed1997

Variations in pigment and carbohydrate content of gallbladder bile affect accurate quantitation of total protein when using the fluorescamine method.

BACKGROUND: Despite solute dilution and reduced total lipid concentrations, an unexplained increase in protein concentration has been reported to occur in the gallbladder bile of cholesterol gallstone patients. METHODS: Solutes in gallbladder bile from gallstone-free controls and from four study groups were measured using standard methods. Total proteins were measured using amino acid analysis and a conventional fluorescamine method. RESULTS: Bile salts and pigment content were greater in gallstone-free controls than in all other study groups, including morbidly obese gallstone-free subjects. Total biliary protein concentration, as determined by amino acid analysis in the gallstone-free control group was higher than in non-obese gallstone patients with multiple stones and in morbidly obese gallstone-free subjects. Total biliary proteins as measured with fluorescamine, however, did not show intergroup differences. A major problem of the conventional fluorescamine assay is shown to be an artefact arising from the high pigment content of the more concentrated samples. CONCLUSIONS: Very dilute gallbladder bile samples are often found in the presence of gallstone disease. This also occurs in morbidly obese subjects, even in the absence of gallstones. Although the contribution of protein secretion/absorption by the gallbladder can also be relevant, especially in the presence of morbid obesity, the protein concentration in gallbladder bile, when accurately measured, generally parallels the concentrations of non-absorbed biliary solutes, reflecting the efficiency of fluid absorption. Measurement of biliary proteins by the conventional fluorescamine method is unreliable in clinical studies in which intergroup differences in pigment content are commonly present.

Adult↗
PubMed1996

The impact of a positive crossmatch upon outcome after liver transplantation.

Recent reports have shown that liver allografts transplanted against a positive lymphocytotoxic crossmatch (CDC+) are susceptible to an increased frequency of rejection, and decreases in patient and graft survival. The implication of a positive flow cytometric crossmatch (FCXM+) in liver transplantation remains controversial. The purpose of this study was to determine what impact a pretransplant IgG crossmatch due to CDC+ or FCXM+ had upon the clinical outcome following liver transplantation. Preoperative crossmatch status was determined prospectively in 110 consecutive liver transplants performed between July 1991 and January 1995. Allografts were divided into three groups: negative crossmatch (NXM), positive flow cytometric crossmatch FCXM+, and positive lymphocytotoxic crossmatch CDC+. Crossmatch status did not impact patient or graft survival. Actuarial patient survival was similar between groups at 12 months (88% vs. 95% vs. 92%, NXM vs. FCXM+ vs. CDC+) and 24 months (81% vs. 93% vs. 92%, NXM vs. FCXM+ vs. CDC+) (P=0.1938). Actuarial allograft survival was similar between groups at 12 months (76% vs. 93% vs. 85%, NXM vs. FCXM+ vs. CDC+) and 24 months (76% vs. 89% vs. 85%, NXM vs. FCXM+ vs. CDC+) (P=0.0738). CDC+ allografts had a significant increase in early rejection episodes compared with NXM (46% vs. 7%, CDC+ vs. NXM) (P=0.003) or FCXM+ allografts (46% vs. 10%, CDC+ vs. FCXM+) (P=0.006). CDC+ allografts experienced significantly more rejection episodes per year than NXM (53% vs. 20%, CDC+ vs. NXM) (P=0.015) or FCXM+ allografts (53% vs. 23%, CDC+ vs. FCXM+) (P=0.02). CDC+ allografts had a significant increase in numbers of additional nonconventional therapeutic interventions compared to NXM allografts (0.9+/-0.5 vs. 0.2+/-0.1, CDC+ vs. NXM) (P=0.039). The presence of cytotoxic antibodies pretransplantation is associated with increased incidences of early rejection, and rejection episodes per year. With careful monitoring and aggressive therapeutic interventions the presence of cytotoxic antibodies are not deleterious to patient or liver allograft survival.

Adult↗
PubMed1996

The hematologic consequences of transjugular intrahepatic portosystemic shunts.

Transjugular intrahepatic portosystemic shunts (TIPS) are a recent innovation in the management of portal hypertension. In 1992, we had previously described an instance of severe hemolysis associated with this procedure. This study was undertaken to define and quantify the true incidence of TIPS-associated hemolysis and its clinical spectrum, as well as to test the hypothesis that portal decompression by TIPS would ameliorate hypersplenism in patients with portal hypertension. A total of 60 patients undergoing TIPS for prevention of recurrent variceal hemorrhage (n = 40) or refractory ascites (n = 20) were studied. Forty patients with cirrhosis who were followed concurrently served as controls. At entry, both groups were comparable with the exception of increased ascites in the TIPS group. A total of 7 instances of intravascular hemolysis were identified in 60 TIPS patients, whereas none occurred in controls. Of these, 4 patients were asymptomatic and detected on routine laboratory testing. Hemolysis led to a greater than 4-g/dL decrease in hemoglobin in 2 patients, 2- to 3-g/dL decrease in 2 others and a 3- to 4-gm/dL decrease in 1 patient. Two patients were able to compensate for hemolysis and did not develop anemia. In all but 1 case, the findings of hemolysis subsided by 12 to 15 weeks; in 1 patient, orthotopic liver transplantation was associated with resolution of the hemolysis. Overall, no significant changes in white blood cell or platelet counts were observed in patients undergoing TIPS despite adequate portal decompression. We conclude that TIPS-induced hemolysis occurs in approximately 10% of subjects. However, it is self-limited and rarely requires intervention. Potential mechanisms of such hemolysis are discussed. TIPS is also not recommended as a means of improving platelet counts in patients with severe hypersplenism.

Adult↗
PubMed1996

Improved sustained response following treatment of chronic hepatitis C by gradual reduction in the interferon dose.

Interferon (IFN) treatment of chronic hepatitis C virus (HCV) is associated with a high rate of relapse. IFN is thought to exert its effect against HCV via direct viral inhibition and immune stimulation. We have hypothesized that relapse following termination of therapy results from the sudden withdrawal of this immune modulatory effect and that gradual reduction in the IFN dose may decrease the incidence of relapse. One hundred six patients with chronic HCV were enrolled into this 24-month controlled, randomized prospective trial. All were treated with 5 mU of interferon-alpha-2b three times a week for 6 months. Patients who achieved biochemical response were randomized to either stop or taper IFN gradually at monthly intervals as follows; 3 mu, 2 mU, 1 mU, and 0.5 mU (all three times a week). 0.5 mU twice weekly and then once weekly. Liver histology was assessed by Knodell index and HCV RNA was measured by a quantitative polymerase chain reaction (PCR) assay. Of the 92 patients who completed the initial 6 months of IFN treatment, 47 (51%) achieved biochemical response. Twenty-one of these patients were randomized to stop IFN treatment and 25 to taper (1 drop-out). At randomization patients were well matched with respect to age, sex, race, serum alanine transaminase (ALT), and liver histology. Biochemical relapse was observed in 19 of 21 (91%) patients who stopped IFN treatment compared with only 60% who tapered IFN (P= .04). Virological relapse occurred in 90% of patients who stopped and only 48% of persons who tapered IFN therapy. At completion of the 24-month study patients who achieved long-term sustained biochemical response had a significantly lower mean Knodell score (3.5 vs. 6.5) and a significantly greater number were HCV RNA negative in serum (85% vs. 18%) compared with relapsers. We conclude that gradual reduction in IFN dose is associated with a significant higher rate of sustained response and clearance of HCV RNA from serum compared with abruptly stopping treatment. This in turn is associated with a significant improvement in hepatic histology supporting the premise that response to IFN therapy can prevent progression to cirrhosis.

Adult↗
PubMed1996

Transjugular intrahepatic portosystemic shunts for patients with active variceal hemorrhage unresponsive to sclerotherapy.

BACKGROUND & AIMS: Despite urgent sclerotherapy, active variceal hemorrhage has a 70%-90% mortality rate in patients with advanced age, sepsis, renal or pulmonary compromise, tense ascites, or deep coma. The aim of this study was to test the safety and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) performed semiemergently and preceded by stabilization by balloon tamponade in such patients. METHODS: Patients with actively bleeding esophageal or contiguous gastric varices despite sclerotherapy were assessed for risk of dying after emergent portacaval shunt. Those considered to be at high risk were stabilized by balloon tamponade and vasopressin/nitroglycerin and TIPS placed semiurgently within 12 hours. Balloon tamponade and pharmacological therapy were discontinued within 24 hours after TIPS in all cases. RESULTS: Thirty-two patients met entry criteria, and 2 were excluded due to portal vein thrombosis. TIPS was successfully placed in 29 of 30 patients and achieved hemostasis in all. Thirty-day and 6-week survival rates were 63% and 60%, respectively; in those without aspiration, the 6-week survival rate was 90%. After a median follow-up period of 920 days, 46% of the original cohort was alive. Only 2 episodes of early rebleeding and 4 late rebleeds occurred. Eight patients developed encephalopathy. Stent stenosis requiring dilation occurred in 6 of 11 patients within 6 months. CONCLUSIONS: TIPS is highly effective as salvage therapy in high-risk patients with active variceal hemorrhage despite endoscopic sclerotherapy.

Adult↗
PubMed1996

Use of hepatic lidocaine metabolism to monitor patients with chronic liver disease.

Lidocaine is converted to its primary metabolic product monoethylglycinexylodide (MEGX) via cytochrome P-4503A4 within the liver. A steady-state concentration of MEGX appears in serum within 15 min following the intravenous administration of lidocaine. The present article reviews some of the data suggesting that this MEGX value can be utilized to assess hepatic function. MEGX production declines stepwise with the severity of chronic hepatitis. In patients with cirrhosis, MEGX declines further with worsening Child class. Nearly all persons with MEGX of < 20 ng/ml had cirrhosis confirmed upon histologic evaluation. Severe life-threatening complications of cirrhosis were observed only in patients with MEGX production below 20 ng/ml. One-year survival for patients with an MEGX value of < 10 ng/ml was only 50%. In contrast, 1-year survival for patients with MEGX of > 10 ng/ml was approximately 80%. These data suggest that MEGX could be utilized as an accurate test of hepatic function and to predict morbidity and mortality related to complications of chronic liver disease. However, this test does have several limitations. There is wide interpatient variability between MEGX and hepatic histology, which severely impairs the ability of this test to accurately predict hepatic histology. In addition, MEGX is affected by gender and several medications. However, since MEGX does decline stepwise with advancing histology in any given patient, the available data suggest that serial monitoring of MEGX could be utilized to track hepatic metabolic capacity in patients with chronic hepatitis and cirrhosis.

Anesthetics, Local↗
PubMed1995

Prophylaxis against gallstone formation with ursodeoxycholic acid in patients participating in a very-low-calorie diet program.

OBJECTIVE: To determine whether prophylactic treatment with ursodeoxycholic acid can prevent gallstone formation in persons participating in a very-low-calorie weight reduction diet program. DESIGN: Multicenter, double-blind, placebo-controlled, multidose clinical trial. Patients were treated with placebo or with 300 mg/d, 600 mg/d, or 1200 mg/d of ursodeoxycholic acid. SETTING: 31 Health Management Resources weight management centers. PATIENTS: 1004 patients were initially enrolled in a 16-week, 520-kcal/d, Health Management Resources liquid protein diet program. All patients had a body mass index of 38 kg/m2 or more and a normal gallbladder ultrasonogram before study entry. Bile analysis was done in 32 patients. MEASUREMENTS: Body weight and body mass index were measured before the diet was started and at 2-week intervals for 16 weeks. Gallbladder ultrasonography was done before enrollment and after 8 and 16 weeks of dieting. Bile was obtained by endoscopy and analyzed for cholesterol crystals and lipid levels. RESULTS: Mean body weight for all patients at the start of dieting was 128.2 kg +/- 23.2 kg; mean initial body mass index was 44.2 kg/m2 +/- 6.0 kg/m2. Gallstones developed in 28% (95% CI, 22% to 35%) of patients receiving placebo, in 8% (CI, 5% to 13%) of patients treated with 300 mg/d of ursodeoxycholic acid, in 3% (CI, 1% to 7%) of patients treated with 600 mg/d of ursodeoxycholic acid, and in 2% (CI, 0.5% to 5%) of patients treated with 1200 mg/d of ursodeoxycholic acid. The differences between patients receiving placebo and patients receiving ursodeoxycholic acid were statistically significant. The percentage of ursodeoxycholic acid in bile increased stepwise with increasing doses of ursodeoxycholic acid. CONCLUSIONS: Ursodeoxycholic acid, 600 mg/d, is highly effective in preventing gallstone formation in patients having dietary-induced weight reduction.

Adolescent↗
PubMed1995

Effect of NSAIDs on gallbladder bile composition.

Secretion of gallbladder mucin is an important step in gallstone pathogenesis. Previous studies have demonstrated that aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) can both inhibit gallbladder mucin secretion and prevent gallstone formation in animal models of cholesterol gallstone disease. The present study was performed to determine if chronic NSAID use was associated with a reduction in the mucin content or affected the lipid components of human gallbladder bile. Four groups of patients were identified retrospectively from a cohort of 230 morbidly obese patients who underwent gastric bypass surgery. The index group consisted of 18 patients who were found to have gallstones at gastric bypass surgery and had a history of chronic NSAID use. Three other patient groups were identified from the cohort by matching this index population for sex, race, and age according to the following criteria: (1) patients with gallstones who had not utilized NSAIDs, (2) patients without gallstones but with chronic NSAID use, and (3) patients without gallstones and without a history of NSAID use. Gallbladder bile was obtained from all patients by direct aspiration from the gallbladder at the time of surgery. Patients with gallstones had a significantly (P < 0.02) greater concentration of gallbladder mucin in their gallbladder bile compared to patients without gallstones (0.897 +/- 0.226 vs 0.173 +/- 0.039 mg/ml). Among gallstone patients, gallbladder mucin was reduced in those patients with a history of chronic NSAID use (1.18 +/- 0.43 vs 0.74 +/- 0.19 mg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗