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Biomedical subjects

A Reuben

Publications and source records attributed to A Reuben.

At least 19 recordsLinked to original sources
PubMed2001

Long-term management of the liver transplant patient: diabetes, hyperlipidemia, and obesity.

1. As long-term survival improves after liver transplantation, cardiovascular complications are emerging as a major cause of late morbidity and mortality. It seems reasonable to correct the potentially reversible cardiovascular risk factors of diabetes, hyperlipidemia, and obesity, in addition to hypertension. 2. The results of liver transplantation in diabetics are acceptable in terms of morbidity, mortality, and prevalence of posttransplant diabetes, but the poor outcomes described in some series suggest that more extensive testing for macro- and microvascular disease may become necessary. 3. The management of diabetes in liver transplant recipients is not substantially different from its management in non-transplant patients, except that steroid reduction or withdrawal and minimizing doses of calcineurin inhibitors are beneficial. 4. Hyperlipidemia occurs in all solid-organ transplantation, with prevalence rates the lowest for liver transplant recipients. Following liver transplantation, between 15% and 40% of recipients on average have increased plasma cholesterol levels and about 40% have hypertriglyceridemia. Dietary changes, weight reduction, exercise and statins are the mainstays of therapy. 5. Retrospective studies suggest that long-term survival of obese recipients after liver transplantation does not differ from nonobese recipients. Posttransplant weight gain occurs in most recipients, and approximately two thirds become overweight. The management of posttransplant obesity is similar to that in non-transplant settings.

Diabetes Complications↗
PubMed2001

Hepatopulmonary syndrome occurring after orthotopic liver transplantation.

Hepatopulmonary syndrome (HPS) is an infrequent complication of liver cirrhosis. Orthotopic liver transplantation (OLT) has gained increasing acceptance as a treatment modality for HPS, although there have been reports of HPS developing after OLT with documented recurrence of cirrhosis. We describe the case of a 9-year-old boy who underwent OLT at 7 months of age because of biliary atresia. He subsequently developed HPS in the setting of chronic rejection without cirrhosis or evidence of portal hypertension. Re-OLT resulted in resolution of HPS and a good clinical outcome.

Child↗
PubMed2001

Endoscopic treatment of post-liver transplantation biliary leaks with stent placement across the leak site.

BACKGROUND: Biliary tract leaks occur in over 10% of patients undergoing liver transplantation and are the most common cause of biliary tract-related death in these patients. A number of treatment options are available, but a standard approach has not been established. METHODS: Twenty-six patients were retrospectively studied who had post-transplantation leaks develop with special reference to those who underwent endoscopic placement of a "leak-bridging" stent. RESULTS: Endoscopic retrograde cholangiography was performed in all cases with no procedure-related complications. Twenty-four patients had a leak-bridging stent, 1 a transpapillary stent, and 1 a nasobiliary drain. Leak resolution occurred in 23 cases (88%) after initial stent placement. The median time to stent removal was 8 weeks. Three patients did not respond to initial treatment; 2 were successfully treated with another stent and a single patient required surgical repair. Four deaths occurred during follow-up, all unrelated to the biliary leak. CONCLUSIONS: Placement of a leak-bridging stent is a safe and effective initial treatment for post-liver transplantation biliary leaks.

Bile↗
PubMed2001

Ninety patients with nonalcoholic steatohepatitis: insulin resistance, familial tendency, and severity of disease.

OBJECTIVE: Nonalcoholic steatohepatitis (NASH) is a common but poorly understood liver disease. Our aim was to study a large group of patients referred for Hepatology consultation to further characterize this disorder, in particular its demographics and range of severity. We also sought to better understand its etiology and its relationship to the insulin resistance syndrome, known as the metabolic syndrome or syndrome X. METHODS: Retrospective review of 90 patients seen over a 4-yr period. RESULTS: Ninety patients aged 14-70 with NASH seen at the Liver Clinics at either the University of Tennessee or the Medical University of South Carolina. Eleven had complications of portal hypertension and seven of these had undergone or were awaiting transplantation. NASH was seen in nine families either in siblings or in subsequent generations. Diabetes or insulin resistance were present in almost all in this cohort of patients with NASH. Diabetes, hyperlipidemia, hypertension, and atherosclerotic disease, the components of syndrome X, were common in this population. CONCLUSION: NASH affects males and females equally, and presents over a wide age range. Despite its usually benign course, 28% of patients had cirrhosis and almost half of those had complications of portal hypertension, necessitating liver transplantation. Obesity was common in affected patients and cirrhosis was more common in the morbidly obese. Familial clustering was common, with 18% of patients having a similarly affected first degree relative. The clinical features that define syndrome X (diabetes, hypertension, hyperlipidemia, and atherosclerotic disease) are common in affected patients. Studies of glucose tolerance demonstrated unsuspected diabetes in six, and insulin resistance (the hallmark of syndrome X) in 85% of those tested. We hypothesize that NASH is a disorder of genetic etiology and is the hepatic manifestation of syndrome X, the insulin resistance syndrome.

Adolescent↗
PubMed2000

Oncostatin M: a cytokine upregulated in human cirrhosis, increases collagen production by human hepatic stellate cells.

BACKGROUND/AIMS: Hepatic stellate cells are predominantly responsible for the increased extracellular matrix seen in cirrhosis. The cytokine oncostatin M has been implicated in fibrogenesis in vitro in other cell types and in vivo in other tissues, although its effect on hepatic stellate cells or in cirrhosis is unknown. METHODS: To examine the effect of oncostatin M on collagen production by human hepatic stellate cells in culture, collagen protein was measured and collagen alpha2(1) mRNA was quantified by Northern analysis. Tissue inhibitor of metalloproteinase-1 (an inhibitor of collagen degradation) mRNA was measured in response to oncostation M stimulation. To explore the potential biological significance of this work to human liver disease, oncostatin M messenger RNA in normal and cirrhotic human liver was measured. RESULTS: Oncostatin M induced in a 2-fold increase in collagen secretion. The potency of induction of collagen protein secretion was equal to that observed after transforming growth factor beta stimulation. An increase in endogenous collagen alpha2(1) mRNA could not be detected. This suggested a post-transcriptional mechanism for the increase in collagen protein. In response to oncostatin M stimulation, there was a 2-fold increase in the tissue inhibitor or metalloproteinase-1 mRNA. Oncostatin M mRNA was detected in 6/6 cirrhotic livers and 1/7 normal livers after 28 PCR cycles. CONCLUSION: These results suggest that oncostatin M expression is upregulated in cirrhosis where it may have a role as a profibrogenic cytokine in hepatic stellate cells.

Cells, Cultured↗
PubMed2000

Alcohol-acetaminophen syndrome. Even moderate social drinkers are at risk.

In long-term alcohol users, the syndrome of hepatotoxicity from acetaminophen taken in therapeutic or modestly excessive doses is distinctive. It is characterized by striking elevation of transaminase levels and the potential for acute liver failure with high morbidity and mortality rates. A high index of suspicion should be maintained; in any patient with evidence of acute hepatic injury, a complete history of over-the-counter drug use should be obtained and acetaminophen levels checked. If there is doubt about the dose or time of ingestion, one should err on the side of treatment with acetylcysteine, because it is both effective and safe. Therapy should be initiated as early as possible, but even late administration may be of benefit. Timely contact with a medical center that has liver transplantation capabilities should be made before encephalopathy becomes advanced. Heightened awareness of this preventable and treatable condition is needed by healthcare providers and acetaminophen users alike. Because the minimum safe dose of acetaminophen is not known in the setting of chronic alcohol use, it seems prudent in such situations to avoid acetaminophen altogether, especially during brief periods of abstinence.

Acetaminophen↗
PubMed1999

Impact of segmental grafts on pediatric liver transplantation--a review of the United Network for Organ Sharing Scientific Registry data (1990-1996).

PURPOSE: The aim of this study was to assess the relative impact of segmental grafts from cadaveric and living donors on outcomes in 3,409 pediatric transplants (<18 years) between 1990 and 1996. METHODS: Analysis of the United Network for Organ Sharing (UNOS) Scientific registry data from 1990 to 1996 was performed. RESULTS: Liver grafts consisted of 2,636 whole grafts (WLG), 246 liver donor grafts (LDG), 89 split liver graft (SLG), and 438 reduced-size grafts (RSG). Although the number of pediatric transplants were unchanged between 1990 and 1996, segmental grafts made up an increasing proportion from 14.5% to 29.2%, and WLG decreased proportionately. The increase among segmental grafts occurred for LDG (threefold), followed by SLG (53%) and RSG (50%). One-year graft and patient survival rates for 3,409 transplants were 69.7% and 81.9%, respectively and were significantly higher (P<.001) in nonhospitalized patients than in hospitalized patients (79.8% and 91.3% v 61.0% and 73.7%). LDG graft survival (75.9%) was comparable with WLG(70.9%) but significantly better at 1 year than SLG (60.3%, P = .007) and RSG (61.1%, P = .001), even after excluding retransplants and ICU patients. Patient survival rates were not different statistically between groups. A separate analysis of outcomes in recipients less than 1 year of age suggested significantly better graft and patient survivals for LDG (83.3% and 89.4%) than for WLG (62.3% and 76.5%) and RSG (62.7% and 75%). CONCLUSIONS: Segmental liver grafts from cadaveric and living donors constitute an increasing proportion of pediatric transplants. Survival rates of cadaveric segmental graft are inferior to those of live donor segmental grafts even after adjustment for medical condition. Live donor grafts demonstrate consistently superior graft and patient outcomes in pediatric recipients less than 1 year of age, and should be promoted aggressively as a solution to the critical shortage of size matched grafts in small recipients.

Age Factors↗
PubMed1999

Influence of fibrinogen and haematocrit on erythrocyte sedimentation kinetics.

This study investigates the influence of haematocrit, fibrinogen concentration and fibrinogen availability (amount of fibrinogen per red blood cell) on erythrocyte sedimentation. The Westergren technique was applied to blood samples from 36 subjects and to their blood manipulated to haematocrits of 10, 20, 30 and 40%. Readings were taken every 10 minutes for 300 minutes. Previous studies indicate that erythrocyte sedimentation occurs in three phases. In this study, we show that haematocrit has little influence on either the rate of fall of particles in the first phase (m1) or the duration of the first phase. This is also true for fibrinogen availability and for fibrinogen concentration at low haematocrits. At high haematocrits m1 increases with fibrinogen concentration. The rate of fall of rouleaux during phase 2 (m2) and ESR60 both decrease exponentially with haematocrit and increase linearly with fibrinogen concentration. While m2 is more closely correlated to fibrinogen availability than to fibrinogen concentration or to haematocrit, this is not the case for ESR60. Thus haematocrit, fibrinogen concentration and fibrinogen availability are more important to the velocity of sedimentation in the second phase than to the sedimenting velocity during phase 1 or to the duration of phase 1.

Adult↗
PubMed1996

Noninvasive assessment of hepatic triglyceride content in humans with 13C nuclear magnetic resonance spectroscopy.

Hepatic lipid content was assessed noninvasively in 15 patients with hepatic steatosis by 13C nuclear magnetic resonance (NMR) spectroscopy, and compared in a double-blind fashion with histological grading and morphometric quantitation of fat in liver biopsies taken within 2 weeks of the study. The lipid content in the liver biopsies was expressed as the volume fraction of total parenchyma occupied by fat. Hepatic triglyceride content was determined by comparing the 13C NMR signal intensity in vivo with the signal intensity obtained from a lipid phantom of known concentrations. There was an approximately 30-fold increase in the 13C NMR signals of the saturated carbons (methyl/methylene [CH2]n) region of hepatic triglycerides from patients with grade 4 steatosis compared with those with grade 0, yielding a good dynamic range for measuring hepatic triglyceride content. The correlation coefficient between the morphometric and 13C NMR techniques was 0.89 (P < .01). These studies demonstrate that 13C NMR spectroscopy can be used to noninvasively assess hepatic triglyceride content in humans. This method may be clinically useful for diagnosis and follow-up of patients with hepatic steatosis.

Adult↗
PubMed1995

Multiple focal nodular hyperplasia of the liver associated with hemihypertrophy and vascular malformations.

A case of multiple focal nodular hyperplasia of the liver occurring in a 22-year-old woman with musculoskeletal hemihypertrophy and anomalous vascular supply to the liver is described. The patient had Klippel-Trénaunay-Weber syndrome and abdominal pain and tender massive hepatomegaly. Visceral angiography showed marked dilatation of the celiac axis and both the main trunk and peripheral branches of the hepatic artery. Large abdominal veins drained from the dome of the liver into the hepatic veins. The vascular anomalies were evident on contrast-enhanced computed tomography and magnetic resonance imaging. Multiple focal nodular hyperplasia was confirmed by laparoscopic liver biopsy. The findings in this patient support the concept that multiple focal nodular hyperplasia characteristically occurs in a syndromic form and is induced by an irregular arterial supply in the liver, with localized hyperfusion that leads to nodular areas of hepatocyte hyperproliferation.

Adult↗
PubMed1995

Relationship of aminotransferases to liver histological status in chronic hepatitis C.

OBJECTIVES: Serum aminotransferase levels characteristically fluctuate in chronic hepatitis C, but their relationship to grade (i.e., inflammatory activity) and stage (i.e., degree of fibrosis) of liver disease is uncertain. We therefore correlated aminotransferase levels and liver biopsy findings in 90 patients with serologically confirmed chronic hepatitis C. METHODS: Mode of transmission; disease duration; symptoms and signs of liver disease; alcohol intake; autoantibody, HIV, and hepatitis B virus status; and liver biochemistries were obtained from records. Liver biopsies were 1) given a morphological diagnosis, 2) evaluated for features of chronic hepatitis C, and 3) scored with a histological activity index. RESULTS: Individual aminotransferase levels were not related to clinical or laboratory variables, nor were they reliably predictive of morphological diagnosis. No histological characteristics were associated with a particular range of aminotransferase values, except aminotransferases > 350 U/L, which were associated with piecemeal necrosis. Although mean values of aminotransferases were significantly lower among patients with chronic persistent hepatitis (CPH) (i.e., with minimal activity) compared with chronic active hepatitis (CAH) (mild to moderate activity) (ALT 110 U/L +/- 71 SD vs 256 +/- 211; AST 57 U/L +/- 34 vs 123 +/- 88) and in the absence of piecemeal necrosis compared with in its presence (ALT 133 +/- 84 vs 207 +/- 149; AST 73 +/- 47 vs 120 +/- 83), overlap of values was considerable between different histological groups. CONCLUSION: Aminotransferases do not predict liver histological status in chronic hepatitis C, although > or = 10-fold elevations suggest that piecemeal necrosis is present.

Adult↗
PubMed1991

PBC 95k, a 95-kilodalton nuclear autoantigen in primary biliary cirrhosis.

We have identified a novel antinuclear antibody (ANA) in the sera of patients with primary biliary cirrhosis (PBC). Sera from 22 of 50 PBC patients stained the nuclei of HEp-2 cells in a pattern of 5-20 discrete dots, on indirect immunofluorescence. Typically, the titers were higher than 1:1,280. This staining pattern was seen in only 4 of 1,240 ANA-positive samples from patients with other connective tissue diseases, and in none of the ANA-positive sera from 49 patients with other liver diseases. Sera which stained the nuclear dots bound a 95-kd polypeptide in immunoblots of HeLa nuclei and in immunoprecipitates of 35S-methionine-labeled HeLa extracts. Affinity-purified antibodies from the 95-kd protein reproduced the nuclear dot immunofluorescence staining pattern, demonstrating that this polypeptide is located in the nuclear dots. ANA of this type, therefore, occur in 44% of patients with PBC, and they appear to be specific for PBC. These antibodies bind a 95-kd protein that is discrete and is scattered throughout the nucleus.

Autoantigens↗
PubMed1991

Comparison of two schedules of cefoperazone plus aztreonam in the treatment of neutropenic patients with fever.

Cancer patients were randomized to receive an every 4 hour or every 8 hour schedule of cefoperazone plus aztreonam during 617 febrile episodes. The overall response rate for the 478 evaluable episodes was 76% and there was no difference in response rate between the two schedules. The response rate was 79% for cases of pneumonia and 63% for cases of bacteremia. Only 50% of the microbiologically documented infections caused by gram-positive organisms responded whereas 95% of gram-negative infections, including all of those caused by Pseudomonas aeruginosa, responded. Response rates were lower among patients whose neutrophil counts decreased during therapy than among those whose neutrophil counts increased (64% vs. 85%, p = 0.008). Side-effects that were possibly or probably related to antibiotic therapy were observed during 11% of the episodes. The most common side-effects were diarrhea and rashes including one case of Stevens-Johnson syndrome. Three patients developed a coagulopathy during therapy. Cefoperazone plus aztreonam proved to be an effective combination for treatment of gram-negative infections and fever of unknown origin in cancer patients and an every 8-hour schedule of administration was as effective as an every 4-hour schedule. Approximately half of the patients with gram-positive infections required additional antibiotics for successful therapy.

Aztreonam↗
PubMed1991

Propranolol ameliorates the development of portal-systemic shunting in a chronic murine schistosomiasis model of portal hypertension.

We investigated the role of early portal hypotensive pharmacotherapy in preventing the development of portal-systemic shunting in a portal hypertensive model of chronic murine schistosomiasis induced by infecting C3H mice with 60 cercariae of Schistosoma mansoni. Propranolol was administered in drinking water to 20 animals for a period of 6 wk at a dose of 10 mg.kg-1d-1, starting at 5 wk of schistosomal infection. 32 age-matched mice with chronic schistosomal infection served as controls. All animals were studied 11 wk after the infection. Compared with controls the portal pressure (10.8 +/- 0.40 mmHg) was significantly lower (P less than 0.001) in the propranolol-treated animals (7.9 +/- 0.80 mmHg). Portal-systemic shunting was decreased by 79%, from 12.2 +/- 3.34% in controls to 2.5 +/- 0.99% in the propranolol group (P less than 0.05). Portal venous inflow was reduced by 38% in the propranolol treated animals (2.50 +/- 0.73 ml/min; n = 6) compared with controls (4.00 +/- 0.34 ml/min; n = 8; P less than 0.05). The worm burden, the granulomatous reaction, the collagen content of the liver, and the serum bile acid levels were not significantly different between the two groups of animals. These results demonstrate that in chronic liver disease induced by schistosomiasis, the development of portal-systemic shunting can be decreased or prevented by the reduction of flow and pressure in the portal system.

Animals↗
PubMed1991

Effect of insulin and plasma amino acid concentration on leucine metabolism in cirrhosis.

Clinically stable patients with cirrhosis demonstrate insulin resistance with regard to glucose metabolism. However, much less is known about the two major factors, insulin and plasma amino acid concentration, that regulate protein metabolism in cirrhotic patients. To examine this question, we performed paired euglycemic insulin clamp studies in combination with 14C-leucine and indirect calorimetry. In the first study insulin alone was infused, and the plasma amino acid concentration was allowed to decline. During the second study a balanced amino acid solution was infused with insulin to increase the total plasma amino acid concentration approximately twofold. Insulin-mediated glucose disposal (4.68 vs. 6.45 mg/kg-min, p less than 0.01) was significantly impaired by 30% in cirrhotic patients during both insulin clamp studies. In the postabsorptive state, cirrhotic patients manifested low plasma leucine (76 vs. 102 mumol/L) and alpha-ketoisocaproate (19 vs. 30 mumol/L) concentrations, but all parameters of leucine turnover were normal. When insulin alone was infused, the endogenous leucine flux (an index of protein degradation) declined similarly in cirrhotic patients (30.8 mumol/m2-min) and control (26.9) subjects, and this was accompanied by a similar decrease in plasma leucine concentration (31% vs. 33%). The decline in circulating leucine concentration was accompanied by a parallel decline in leucine oxidation (5.1 vs. 4.6 mumol/m2-min) and nonoxidative (28.9 vs. 26.0 mumol/m2-min) leucine disposal, which were of similar magnitude in cirrhotic patients and control subjects, respectively. In both cirrhotic patients and control subjects, combined hyperinsulinemia/hyperaminoacidemia elicited a similar stimulation of nonoxidative leucine disposal (an index of protein synthesis) and leucine oxidation while causing a greater suppression of endogenous leucine flux than observed with insulin alone. Thus the suppressive effect of insulin on protein degradation and the stimulatory effect of insulin/amino acid infusion on protein synthesis are not impaired in cirrhotic patients, demonstrating a clear-cut dissociation between the effects of insulin on protein and glucose metabolism.

Amino Acids↗