PubMed Health⌕ Search

Biomedical subjects

M Weltman

Publications and source records attributed to M Weltman.

10 recordsLinked to original sources
PubMed2003

Autoimmune hemolysis associated with primary biliary cirrhosis responding to ursodeoxycholic acid as sole treatment.

Coombs' positive autoimmune hemolytic anemia (AIHA) has been rarely described in association with primary biliary cirrhosis (PBC). The previously reported cases have responded to treatment with a combination of corticosteroids and ursodeoxycholic acid (UDCA). We report a case of AIHA occurring in association with PBC, which has responded to treatment with UDCA alone. Possible mechanisms of autoimmune hemolysis in this patient include bile salt induced immune dysregulation and direct damage to red cell membranes by bile salts leading to exposure of neoantigens and development of red cell autoantibodies. A trial of UDCA as a single agent should be considered as initial treatment in this rare disorder.

Anemia, Hemolytic, Autoimmune↗
PubMed2000

Which patients with hepatitis C develop liver complications?

To identify variables that are independent predictors of adverse outcomes in chronic hepatitis C, we analyzed a cohort of 455 patients followed for a median of 4.7 years. Associations were sought between demographic and behavioral factors, hepatitis C virus (HCV) genotype, liver histology and liver tests at entry, and development of liver complications, hepatocellular carcinoma (HCC), hepatic transplantation and liver-related death. Independent predictors were identified by multivariate analysis. The following were associated with a significantly higher rate of liver complications: age; birth in Asia, Europe, Mediterranean region, or Egypt; transmission by blood transfusion or sporadic cases; HCV genotypes 1b and 4 (compared with 1/1a); fibrosis stage 3 or 4 (cirrhosis); serum albumin; bilirubin; prothrombin time; and alpha-fetoprotein. However, the only independent predictors of liver-related complications were sporadic transmission (P <.001), advanced fibrosis (P =.004), and low albumin (P <.001). The corresponding independent risk factors for HCC were male gender (P =. 07), sporadic transmission (P <.001), and albumin (P <.001); bilirubin (P =.02) was an additional predictor of transplantation or liver-related death. It is concluded that only patients with advanced hepatic fibrosis or cirrhosis, are at risk of developing hepatic complications of chronic hepatitis C during 5-year follow-up. Among such patients, abnormalities in serum albumin, bilirubin, or prothrombin time indicate a high probability of complications. Patients without definite risk factors for HCV (sporadic cases) are at higher risk of complications, possibly because of interaction between older age, duration of infection, country of birth, and HCV genotypes 1b and 4.

Adult↗
PubMed1999

Does steatohepatitis impair liver regeneration? A study in a dietary model of non-alcoholic steatohepatitis in rats.

BACKGROUND: Impaired liver regeneration is a feature of alcoholic hepatitis, but the relative importance of alcohol, nutritional imbalance and inflammatory mediators in causing this effect is unclear. Non-alcoholic steatohepatitis (NASH) is a form of liver disease with similar morphology to alcoholic hepatitis, but the effect of this disorder on liver regeneration is unclear. We, therefore, examined the status of liver regeneration in a rat nutritional model of hepatic steatosis with inflammation, which is morphologically identical to NASH in humans. METHODS: Male Wistar rats received a methionine-choline-deficient diet (MCDD) for 4 weeks before experiments and both isocaloric pair-fed and ad libitum-fed rats were used as controls. Following partial hepatectomy (68%), the extent of hepatic regeneration was determined 24 h later using [3H]-thymidine incorporation and restitution of liver mass. RESULTS: There was no significant difference of [3H]-thymidine incorporation in MCDD-fed, pair-fed and ad libitum-fed rats (80+/-27, 78+/-11 and 80+/-6.3 d.p.m./microg DNA, respectively). Similarly, restituted liver masses in three groups of rats were not significantly different (17+/-3.8, 18+/-1.8 and 17+/-3.1% initial liver weight, respectively). CONCLUSIONS: The similarities in hepatic histology and cytochrome P450 2E1 induction between this nutritional model of hepatic steatohepatitis and alcoholic steatohepatitis imply that these two disorders share pathogenetic mechanisms. However, liver regeneration is not altered by NASH in rats, indicating that the nutritional and inflammatory changes that appear similar to those of alcoholic liver disease do not cause impairment of liver regeneration.

Animal Feed↗
PubMed1999

Risk factors for development of hepatocellular carcinoma among Australians with hepatitis C: a case-control study.

BACKGROUND: Older patients with cirrhosis due to hepatitis C are at risk of developing hepatocellular carcinoma (HCC), but additional risk factors may vary between countries. AIM: In the present study, we sought to identify additional risk factors for HCC among a cohort of Australian patients with chronic hepatitis C. METHODS: Case-control study of patients with advanced fibrosis stage hepatitis C who developed HCC during five-year follow up at a referral liver clinic. Cases were compared to twice the number of age-matched patients with chronic hepatitis C of similar fibrotic severity who did not develop HCC over a similar interval, using conditional logistic regression analysis (CLRA) and multivariate analysis. The main outcome measures were demographic and disease-related variables at first presentation in relation to the development of HCC. RESULTS: HCC developed in 17 cases, an annual incidence among those considered to be at risk of 2%. The duration of follow up since first assessment was comparable among the cases and 34 selected age-matched controls (4.1 and 5.2 years respectively, p=0.5). Cases were more often male (p=0.03), born in Asia (p=0.05), and had poorer liver function as indicated by serum albumin concentration (p=0.02). Anti-hepatitis B core-antibody (anti-HBc) was detected in 59% (ten/17) of cases, compared to 21% (seven/34) of the controls (p=0.01). No patient with a sustained response to interferon developed HCC during follow up. There were no significant differences in the mode of HCV transmission, HCV genotype, alcohol exposure, serum bilirubin level or prothrombin time between the cases and the controls. Although the data set was small, multivariate CLR analysis identified serum albumin < or = 35 g/L and anti-HBc positivity to be independent risk factors for development of HCC. CONCLUSIONS: Among older Australian patients (over the age of 40 years) with advanced fibrosis stage hepatitis C, the annual incidence of HCC is about 2%. Those who have low serum albumin and evidence of previous exposure to hepatitis B virus (anti-HBc positivity) appear to have the highest risk of developing HCC during follow up, but males and those born in Asia could also be at increased risk.

Aged↗
PubMed1998

How much does alcohol contribute to the variability of hepatic fibrosis in chronic hepatitis C?

In order to determine the contribution of alcohol intake to the severity of hepatic fibrosis in patients with chronic hepatitis C, we studied associations between various levels of alcohol intake, other demographic variables and semiquantitative liver histology in 434 cases of chronic hepatitis C. Clinical, demographic and disease-related data were entered into a relational database. Liver histology was scored according to Scheuer. The average daily alcohol intake for the year preceding liver biopsy (recent exposure) and for earlier periods (past exposure) was categorized into five levels of intake. One-third of patients gave a history of alcohol intake that had exceeded 40 g/day for at least 5 years. By univariate analysis, age, but not recent or past alcohol intake or other baseline variables, was associated with portal score (r = 0.14, P = 0.004), fibrosis score (r = 0.46, P < 0.001), total Scheuer score (r = 0.35, P < 0.001). However, by multivariate analysis, age (P < 0.001), past (but not present) alcohol intake (P < 0.001) and birth in Egypt (P = 0.006) were independently associated with fibrosis score. Age, past alcohol and birth place in Egypt contributed 27% to total variance of the hepatic fibrosis score, while age alone accounted for 23%. Age also independently predicted portal activity (P = 0.02) and total Scheuer score (P < 0.001), whereas past alcohol intake correlated with total Scheuer score (P = 0.002) but not with other histological indices. A separate multivariate analysis was performed on a more homogeneous subgroup of 196 patients who acquired hepatitis C by injection drug use. In this subgroup, age (P < 0.05) and past alcohol (P < 0.05) were independently associated with fibrosis score. In both the overall and subgroup analyses, there was a threshold level of past alcohol intake (>80 g/day) beyond which the risk of fibrosis increased significantly. It is concluded that toxic levels of alcohol exposure for at least 5 years accentuate hepatic fibrosis in hepatitis C but the influence of alcohol appears to be minor compared with age and other variables and is exerted only at toxic levels of intake.

Adult↗
PubMed1996

Halothane-induced liver injury in guinea-pigs: importance of cytochrome P450 enzyme activity and hepatic blood flow.

The basis for susceptibility to halothane-induced liver necrosis in guinea-pigs was examined. In hepatic microsomes, the following were similar in susceptible and resistant animals: total cytochrome (CYP) P450 (P450), phenobarbital-inducible pathways of mixed function oxidation (androstenedione 6 beta- and 16 beta-hydroxylase activities) and the CyP2E1-catalysed pathway of N-nitrosodimethylamine N-demethylase activity. Similarly, immunohistochemical staining of CYP2E1 protein was equivalent in livers from susceptible and resistant guinea-pigs. Prior treatment with the P450-inhibitors, metyrapone and SKF-525A ameliorated halothane-induced liver damage in susceptible animals. Conversely, in resistant guinea-pigs, stimulation of hepatic CYP2E1 activity by treatment with 4-methylpyrazole produced severe hepatotoxicity after re-exposure to halothane. These results confirm the conclusions of others, that P450-mediated metabolism produces halothane-induced liver necrosis in the guinea-pig model but, as in other work, the data fail to explain why no difference in activity of these enzymes could be found between susceptible and resistant guinea-pigs. To establish whether a differential effect on hepatic blood flow between susceptible and resistant guinea-pigs could explain this paradox, studies were performed using a radiolabelled microsphere technique. The effect of halothane on lowering cardiac output was identical in both groups of animals and halothane significantly reduced hepatic arterial but not portal blood flow. The effect on arterial blood flow was more profound in susceptible guinea-pigs (0.67 +/- 0.17% of injected microspheres) than in resistant animals (0.99 +/- 0.13%; P < 0.005). It is concluded that P450-catalysed metabolism and reduced hepatic blood flow are both necessary to produce halothane-induced liver injury in susceptible guinea-pigs, but it is the effect of halothane on hepatic arterial blood flow that differs between susceptible and resistant animals.

Animals↗
PubMed1995

Interferon alfa for chronic active hepatitis B. Long term follow-up of 62 patients: outcomes and predictors of response.

OBJECTIVE: To evaluate the response to treatment with interferon alfa and the long term outcome of patients with chronic active hepatitis B. METHODS: Sixty-two patients with chronic active hepatitis B (43 males, 19 females; age range, 10-67 years) who were treated with interferon alfa at Westmead Hospital between 1984 and 1992 were followed up (mean period of follow-up, 44 months). Thirty-nine patients were treated with interferon alfa-2a and 23 with interferon alfa-2b for a mean of 22.5 weeks. Interferon was given three times a week with a dose range of 3-21 million U. We evaluated pretreatment predictors of response (patient's age, sex, ethnic origin, presence of cirrhosis, serum levels of alanine aminotransferase [ALT] and hepatitis B virus DNA [HBV-DNA]) and the effect of dose and type of interferon. RESULTS: Nine patients had a complete response to treatment with interferon alfa (loss of hepatitis B surface antigen), 26 had a partial response (permanently HBV-DNA negative, hepatitis B e antigen to anti-hepatitis Be seroconversion), eight had a transient response and 19 had no response. All patients with a complete response had normal ALT levels at last follow-up. Histological evidence of hepatic inflammation was significantly reduced in responders. A high pretreatment ALT level and a low HBV-DNA titre were both positive predictors of a favourable response. We found no significant difference in the response to different types of interferon or to high or low dose regimens, or in the responses of patients with cirrhosis. CONCLUSION: Treatment with interferon alfa was associated with prolonged suppression of HBV replication in over half these patients and 14% appear to have been cured of the infection. Suppression of HBV replication is associated with sustained abatement of liver disease.

Adult↗
PubMed1993

A study of immunoglobulin G subclass levels in black and white patients with various forms of obstructive lung disease.

The association of various respiratory disorders with disturbances in immunoglobulin G (IgG) subclass levels is increasingly being recognised. This was a prospective study of the IgG subclass levels in 71 patients (37 white, 34 black) with various respiratory disorders associated with obstructive airways disease. Ten white patients with adult cystic fibrosis were studied, 4 of whom were colonised with Pseudomonas aeruginosa. Alterations in individual subclass levels were seen in these patients and abnormalities noted included a decrease in IgG3 and/or an increase in IgG1 and/or IgG2 levels. Of the 17 black and 16 white patients with asthma, 2 had absent IgG4 levels associated with severe and recurrent respiratory infections, 2 had deficient IgG3 and 1 decreased IgG1 levels. Several patients had increased levels of several IgG subclasses, of which IgG1 was the most commonly affected. Both atopy and recurrent chest infections occurred most often in the latter group of patients. In the studies of 17 black and 11 white patients with bronchiectasis, all but 3 white patients were shown to have some alteration in IgG subclass levels. The commonest deficiencies were an absence of IgG4 (3 cases), and an absence of all subclasses (2 cases). One of the latter patients had an associated deficiency of total IgG and IgM, and the other demonstrated pan-hypogammaglobulinaemia. Abnormalities of IgG subclass levels appear to be commonly associated with several respiratory disorders including recurrent infections, atopy and bronchiectasis.

Adolescent↗
PubMed1975

Neonatal locomotor and long-term behavioral effects of d-amphetamine in the rat.

Locomotor activity in the neonatal rat was found to increase from birth until the beginning of the 3rd week of life, at which time it peaked and then subsequently declined. Subcutaneous injections of both .25 and 2.0 mg/kg of d-amphetamine increased activity in rats 1-21 days of age, with the maximum effect observed at 4 days of age. No tolerance to d-amphetamine was observed after 6 daily injections beginning at 1, 7, or 14 days of age. The decline in the excitatory effects of the drug thus reflected maturational changes in response to it. Consistent with other observations from this laboratory, no persisting effects of the neonatal drug treatment was observed on adult 2-way avoidance learning.

Age Factors↗