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B Combes

Publications and source records attributed to B Combes.

At least 19 recordsLinked to original sources
PubMed1999

Biliary bile acids in primary biliary cirrhosis: effect of ursodeoxycholic acid.

Bile acid composition in fasting duodenal bile was assessed at entry and at 2 years in patients with primary biliary cirrhosis (PBC) enrolled in a randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid (UDCA) (10-12 mg/kg/d) taken as a single bedtime dose. Specimens were analyzed by a high-pressure liquid chromatography method that had been validated against gas chromatography. Percent composition in bile (mean +/- SD) for 98 patients at entry for cholic (CA), chenodeoxycholic (CDCA), deoxycholic (DCA), lithocholic (LCA), and ursodeoxycholic (UDCA) acids, respectively, were 57.4 +/- 18.6, 31.5 +/- 15.5, 8.0 +/- 9.3, 0.3 +/- 1.0, and 0.6 +/- 0.9. Values for CA were increased, whereas those for CDCA, DCA, LCA, and UDCA were decreased when compared with values in normal persons. Bile acid composition of the major bile acids did not change after 2 years on placebo medication. By contrast, in patients receiving UDCA for 2 years, bile became enriched with UDCA on average to 40.1%, and significant decreases were noted for CA (to 32.2%) and CDCA (to 19.5%). No change in percent composition was observed for DCA and LCA. Percent composition at entry and changes in composition after 2 years on UDCA were similar in patients with varying severity of PBC. In patients whose bile was not enriched in UDCA (entry and placebo-treated specimens), CA, CDCA, DCA, and the small amount of UDCA found in some of these specimens were conjugated to a greater extent with glycine (52%-64%) than with taurine (36%-48%). Treatment with UDCA caused the proportion of all endogenous bile acids conjugated with glycine to increase to 69% to 78%, while the proportion conjugated with taurine (22%-31%) fell (P <.05). Administered UDCA was also conjugated predominantly with glycine (87%).

Bile↗
PubMed1999

Association of clonally expanded T cells with the syndrome of primary biliary cirrhosis and limited scleroderma.

Clinical features of the CREST (calcinosis cutis, Raynaud's syndrome, esophageal dysmotility, sclerodactyly, and telangiectasias) syndrome are sometimes exhibited in patients with primary biliary cirrhosis (PBC), but the postulated autoimmune mechanisms behind these conditions are poorly understood. Clonally expanded T cells may play an important role in disease pathogenesis. In this study, overrepresentation of one T-cell receptor beta chain variable region, TCRBV3, was documented in patients with PBC and/or CREST. Overrepresentation of the TCRBV3 gene mRNA was demonstrated by semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR). T cells expressing TCRBV3 were analyzed by flow cytometry, were primarily CD8(+), and contained activated cells as assessed by expression of CD69. Clonally expanded T cells within this population were documented by both complementarity determining region 3 (CDR3) length polymorphism analysis and sequencing of T-cell receptor CDR3 cDNA. TCRBV3(+) clonal expansions were stable when followed for up to 5 years. The results of this study demonstrate that the T-cell repertoire of patients with PBC and CREST is characterized by expanded clonal populations of CD8(+) TCRBV3(+) T cells. These clonal expansions provide evidence that stimulation of clonal populations of CD8(+) T cells is associated with the clinical syndrome of PBC with CREST.

Adult↗
PubMed1999

The effect of ursodeoxycholic acid on the florid duct lesion of primary biliary cirrhosis.

The frequency with which florid duct lesions are seen in needle-biopsy specimens of the liver was assessed in patients with primary biliary cirrhosis (PBC) enrolled in a 2-year randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid (UDCA) versus placebo. Paired biopsy specimens obtained at entry and after 2 years on medication were reviewed blindly and mostly simultaneously by a panel of 5 hepatopathologists who, earlier, had characterized the florid duct lesion, which has been well described in the pathology literature. Florid duct lesions at entry were identified in approximately 36%. Patients with earlier disease showed florid duct lesions much more frequently than those with more advanced disease. The prevalence of florid duct lesions in 60 patients receiving placebo medication fell from 38.3% to 21.7%, P =. 025, over the period of 2 years. The prevalence of florid duct lesions also decreased in the 55 patients receiving UDCA, from 32.7% to 18.2%, P =.046. The prevalences of these lesions in the placebo and UDCA patients at entry and at 2 years were not significantly different from each other. The findings suggest that UDCA does not prevent ongoing bile duct destruction in patients with PBC. Instead, they support the impression that UDCA exerts its beneficial effects by protecting against the consequences of bile duct destruction.

Bile Ducts↗
PubMed1999

The negative effect of repeated equine chorionic gonadotropin treatment on subsequent fertility in Alpine goats is due to a humoral immune response involving the major histocompatibility complex.

In dairy goats, the use of eCG as a convenient hormone for the induction of ovulation is necessary for out-of-season breeding and artificial insemination. However, repeated eCG treatments are followed by decreased fertility in goats inseminated at a fixed time after treatment. In this report, we show the presence of anti-eCG antibodies in plasma of treated goats. A 500 IU eCG injection induces a humoral response, with variable concentrations of anti-eCG antibody being produced in individual goats. The analysis of successive anti-eCG immune responses over several years has demonstrated the existence of different populations of goats, defined as low, medium, and high responders. By the use of two caprine microsatellites located inside (OLADRB) and outside (BM1258) the major histocompatibility complex (MHC), a significant association (p < 0.05) between the anti-eCG antibody response and some MHC-DRB alleles was found. Goats with high antibody concentrations at the time of eCG injection (> 2.5 microg/ml) exhibited a much lower kidding rate than did other females (41.3% vs. 66.7%). Lower fertility of these goats, inseminated at a fixed time after eCG treatment, might be due to the observed delay in estrus occurrence and the preovulatory LH surge.

Animals↗
PubMed1999

Humoral immune response to equine chorionic gonadotropin in ewes: association with major histocompatibility complex and interference with subsequent fertility.

In dairy ewes, the use of eCG as a convenient hormone for the induction of ovulation is necessary for out-of-season breeding and artificial insemination (AI). In this report we show the presence of anti-eCG antibodies in plasma of treated ewes. The major histocompatibility complex (MHC) was involved in the individual variability of the humoral immune responses to eCG. We found significant associations between the anti-eCG response phenotype and some MHC class II alleles. The low immune response phenotype was associated with one MHC class II allele only in Lacaune ewes, and the high immune response phenotype was associated with one MHC class II allele both in Manech and in Lacaune ewes. In herds, the impact of residual anti-eCG antibodies on subsequent fertility after AI seems minimal because of an indirect elimination of high-responder ewes from AI breeding. Therefore, the true magnitude of the association between residual anti-eCG antibody concentration and fertility has been underestimated. An additional experiment without any high-responder female elimination showed a significant correlation between high residual antibody concentrations and lower lambing rate after AI at a fixed time, possibly because of a delayed preovulatory LH surge. The results suggest that anti-eCG antibody concentration is one risk factor for infertility after AI.

Aging↗
PubMed1997

Ursodeoxycholic acid in primary biliary cirrhosis.

In patients with primary biliary cirrhosis (PBC), ursodeoxycholic acid (ursodiol) improves laboratory test markers of cholestasis and hepatic inflammation as well as some hepatic histological features; it also delays histological progression in the early stages of PBC. Ursodiol is well tolerated and safe. Less well substantiated are that ursodiol either improves the quality of life or prevents liver transplantation or that it prolongs survival without transplantation. There are favorable trends for ursodiol in preventing transplantation and prolonging survival, but in the absence of randomized, placebo-controlled trials of sufficient duration, there remain impressions rather than statistically proved, strong conclusions.

Cholagogues and Choleretics↗
PubMed1996

T-cell receptor Vbeta gene utilization in primary biliary cirrhosis.

Semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR) was used to study the T-cell receptor (TCR) beta-chain variable (Vbeta) region gene families expressed by T cells in 28 patients with primary biliary cirrhosis (PBC), 20 normal controls, and 9 patients with other chronic inflammatory hepatic diseases. We hypothesized that activation and clonal proliferation of T cells would lead to biases in the T-cell repertoire of patients with PBC. Freshly harvested T cells from both peripheral blood and liver tissue were examined for evidence of biased Vbeta utilization. Individuals varied considerably in their pattern of Vbeta expression, but several significant differences were noted in the PBC group. In peripheral blood, the mean level of Vbeta6.1,3 expression was greater in PBC patients than in normal controls. In the liver of PBC patients, the mean level of Vbeta6.1,3 expression was even higher than in the peripheral blood, indicating intrahepatic accumulation of these T cells. The mean level of Vbeta6.1,3 expression was not significantly different in the blood compared with liver in patients with other liver diseases. Expression of Vbeta7 and Vbeta13.1 was also significantly greater in the liver than in the blood of PBC patients, but similar trends were also seen in the control liver group. These data show that specific alterations in the TCR repertoire are present in the blood and liver of patients with PBC.

Adult↗
PubMed1996

Steroid therapy of chronic hepatitis: characteristics associated with response in anti-hepatitis C virus-positive and -negative patients.

OBJECTIVES: The goals of this study were to examine responses to corticosteroid-containing therapy in non-B chronic hepatitis patients with different anti-hepatitis C virus (HCV), autoantibody, and biochemical test results and to determine what factors correlate with response. METHODS: Patients with a prior or current history of steroid therapy for putative autoimmune or chronic non-A, non-B hepatitis were assessed. Responses during the first 6 months of therapy were categorized as "complete" (normal aminotransferases for > or = 1 month), "partial" ( > 50% reduction), or "no response." RESULTS: Sufficient data available to permit evaluation in 32 patients. Complete responses were noted in 17, partial responses in 12, and no response in three subjects. By multivariate analysis, only absence of anti-HCV and presence of cirrhosis were independent predictors of response. Nonresponders were found to have lower scores in a proposed autoimmune hepatitis scoring system, but scores of complete and partial responders were not significantly different. Despite a lower likelihood of a complete response, 80% (12/15) of patients with multiantigen positive anti-HCV tests had either partial or complete initial responses to corticosteroid-containing therapy, and, in nine patients, aminotransferases fell to < 2 times the upper limit of normal. All 15 anti-HCV-negative patients, but only three of 15 anti-HCV-positive patients, entered complete responses that were sustained (aminotransferases < twofold abnormal) on regimens containing < 20 mg/day or prednisolone or prednisone. CONCLUSIONS: Although anti-HCV-positive patients frequently exhibit partial initial responses to immunosuppressive therapy, the absence of specific anti-HCV antibodies was better as a predictor of completeness of response than assessment of autoantibodies or degree of biochemical abnormalities.

Adrenal Cortex Hormones↗
PubMed1995

A randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid in primary biliary cirrhosis.

One hundred fifty-one patients with primary biliary cirrhosis (PBC) grouped into four strata based on entry serum bilirubin ( < 2 mg/dL vs. 2 md/dL or greater) and liver histology (stages I, II vs. stages III, IV-Ludwig criteria) were randomized within each stratum to ursodiol or placebo given in a single dose of 10 to 12 mg/kg at bedtime for 2 years. Placebo- (n = 74) and ursodiol- treated (n = 77) patients were well matched at baseline for demographic and prognostic factors. Ursodiol induced major improvements in biochemical tests of the liver in strata 1 and 2 (entry bilirubin < 2), but had less effect on laboratory tests in patients with entry serum bilirubin of > or +2 (strata 3 and 4). Histology was favorably affected by ursodiol in patients in strata 1 and 2 but not in strata 3 and 4. Ursodiol enrichment in fasting bile obtained at the conclusion of the trail was approximately 40% and comparable in all strata. Thus, differences in ursodiol enrichment of the bile acid pool do not explain better responses of laboratory tests and histology found in patients with less advanced PBC. Patients treated will ursodiol tended to develop a treatment failure less frequently that those who received placebo, particularly in strata 1 and 2 (ursodiol 42%, placebo 60%, P = .078). Development of severe symptoms (fatigue/pruritus) and doubling of serum bilirubin were reduced significantly in ursodiol-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Extrahepatic hepatitis B virus DNA sequences in patients with acute hepatitis B infection.

Recent studies have demonstrated the presence of hepadnavirus-related nucleic acids in extrahepatic tissues in various animal models. The prevalence and biological significance of extrahepatic infection in humans remains undetermined. To characterize the tissue distribution and physical state of extrahepatic hepatitis B virus nucleic acids in acute hepatitis infection, we examined serum, liver and multiple extrahepatic tissues obtained at autopsy from two patients with fulminant hepatitis and one patient with resolving hepatitis who died of an unrelated cause. Southern-blot hybridization analysis was used to analyze the physical state of hepatitis B virus-related DNA. Hepatitis B virus-related RNA sequences were examined by slot-blotting total RNA extracted from corresponding tissues. Hepatitis B virus nucleic acids were demonstrated in lymph nodes, spleen, gonads, thyroid gland, kidneys, pancreas and adrenal glands. The most intense signal of hybridization was obtained with DNA extracted from lymph nodes. In general, the levels of hepatitis B virus RNA correlated with the amount of viral DNA. Fast-migrating DNA sequences resembling replicative intermediates and ranging in size from 1 to 3.2 kb were detected in EcoRI digests. Faint high-molecular-weight smears suggesting random integration also were observed. Remarkably, little or no hepatitis B virus nucleic acid was detected in the serum or liver. In control specimens obtained from hepatitis B virus carriers, most hybridizable hepatitis B virus nucleic acid was present in liver, but hepatitis B virus DNA was also detected in extrahepatic tissues. Finally, no specific histological changes were observed in extrahepatic tissues harboring hepatitis B virus.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1989

Methylprednisolone therapy in patients with severe alcoholic hepatitis. A randomized multicenter trial.

STUDY OBJECTIVE: To determine the efficacy of a corticosteroid in reducing the short-term mortality of patients with severe alcoholic hepatitis. DESIGN: Randomized, double-blind, placebo-controlled multicenter trial. SETTING: Four university teaching hospitals. PATIENTS: We enrolled 66 patients with alcoholic hepatitis and either spontaneous hepatic encephalopathy or a discriminant function value greater than 32, calculated using the formula: 4.6 (prothrombin time - control time) + serum bilirubin [in mumol/L]/17.1. Fifty-nine patients (89%) completed the study. Two patients withdrew from the trial. The other 64 patients were hospitalized for the duration of the trial; however, treatment was discontinued in 5 patients because of potential drug toxicity. INTERVENTIONS: Patients were randomly assigned to receive either methylprednisolone (32 mg) or placebo within 7 days of admission. Treatment was given for 28 days. The doses were then tapered over 2 weeks and discontinued. MEASUREMENTS AND MAIN RESULTS: The endpoint of the study was death. Of the 31 recipients of placebo, 11 (35%) died within 28 days of randomization compared with 2 (6%) of the 35 patients given methylprednisolone (P = 0.006). The 95% CI for the difference in mortality was 12% to 70%. In the patients with spontaneous hepatic encephalopathy at entry, 9 of 19 recipients of placebo died (47%) compared with 1 (7%) of the 14 patients given methylprednisolone (P = 0.02). The 95% CI for the difference in mortality was 14% to 66%. The Cox proportional hazards regression model showed the advantage of methylprednisolone over placebo after adjustment for other potentially important prognostic variables (P = 0.004). CONCLUSIONS: Methylprednisolone therapy decreases short-term mortality in patients with severe alcoholic hepatitis manifested either by spontaneous hepatic encephalopathy or a markedly elevated discriminant function value.

Adult↗
PubMed1988

Effect of glutathione depletion on aminopyrine and formaldehyde metabolism.

In previous studies, diethylmaleate (DEM)- and phorone-induced hepatic glutathione (GSH) depletion in rats was accompanied by impaired evolution of 14CO2 from the N-14C-labeled methyl groups of aminopyrine, which in turn was attributed to impaired generation of formaldehyde, its subsequent oxidation to formate, or to some combination of both. In the present study, l-buthionine sulfoximine (BSO)-induced hepatic GSH depletion was also accompanied by decreased evolution of CO2 from aminopyrine, but the extent of the fall in CO2 was less than that induced by DEM or phorone, even though the decrease in hepatic GSH was comparable with all three GSH-lowering compounds. Incubation of freshly prepared normal hepatic microsomes in vitro with the GSH-lowering agents resulted in impaired aminopyrine-N-demethylase (APDM) activity with inhibition by phorone greater than DEM greater than BSO. By contrast, hepatic microsomes prepared from rats pretreated with these compounds had normal APDM activity. 14CO2 evolution from i.p. administered [14C]formaldehyde was not impaired by any of the GSH-lowering compounds. Thus, assessment of APDM activity and formaldehyde metabolism did not unequivocally establish the mechanism(s) by which CO2 evolution from aminopyrine is depressed by DEM, phorone and BSO, although low GSH is likely to impair metabolism of formaldehyde formed in liver after demethylation of aminopyrine. Quantitative differences in the degree of depression of CO2 evolution suggest that at least DEM and phorone exert an additional inhibitory effect by a GSH-independent mechanism. This may involve inhibition of aminopyrine-N-demethylase activity.

Aminopyrine↗
PubMed1988

Prolonged jaundice following ketoconazole-induced hepatic injury.

Two patients developed prolonged and progressive jaundice associated with ketoconazole-induced hepatic injury although the drug was discontinued before or shortly after the onset of symptoms of hepatic toxicity. One patient, who had been jaundiced for eight weeks and was not improving, showed prompt clinical improvement and progressive resolution of jaundice following therapy with prednisolone. Liver biopsy before therapy showed marked cholestasis in all acinar zones and moderately severe fibrosis in the space of Disse. The other patient, who was less severely jaundiced, showed spontaneous resolution although he remained jaundiced for 11 weeks. Liver biopsy performed three weeks after onset of symptoms showed a moderate degree of cholestasis in acinar zone 3 and collagen deposition about the terminal hepatic venules and within the space of Disse. These cases are reported because of the unique clinical course, documentation of the morphologic features, and experience with corticosteroid therapy.

Adult↗
PubMed1988

[Massive fibroma of the round ligament developing as an extraperitoneal abdominal mass].

The authors report the exceptionally rare case of a huge myofibroma of the round ligament. The localization of the myoma was very unusual. It developed from the inguinal insertion of the round ligament; and the fibroma had grown in the abdominal wall between muscle and the peritoneum. Consequently the mass was both abdominal and extra-peritoneal. To our knowledge, such an association has never before been described. In the case described here, the mass was asymptomatic and the patient presented because of her increasing abdominal size. Examination revealed an abdominal mass that almost reached the umbilicus and resembled a four months pregnancy. Ultrasonography showed that the uterus was normal. The mass was a 15 cm by 15 cm tumour of heterogenous structure. As the ovaries were not visualized it was impossible to decide whether the tumour was ovarian, intestinal or peritoneal. Laparotomy was performed with a preliminary diagnosis of a solid ovarian tumour. It was then possible to localize the mass accurately and to define it. Histological examination showed that it was a leiomyoma. Tumours of the round ligament are very uncommon. Among these tumours leiomyomas are the most frequent. Endometriotic tumours come next. Various very rare tumours can also be found. Leiomyoma of the round ligament may arise from each portion of the ligament: abdominal, inguinal or Labium Majus. But both abdominal and extra-peritoneal development from the inguinal insertion of the ligament is rare. They are usually single, and unilateral, and are found by chance.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗
PubMed1987

Carbon tetrachloride-induced morphologic alterations in isolated rat hepatocytes.

Isolated rat hepatocytes were exposed to CCl4 in doses commonly used in in vitro studies and for which we have provided biochemical evidence would induce solvent injury. Rapidly evolving morphologic alterations were observed in the plasma membrane, endoplasmic reticulum, and mitochondria. Swelling and fusion of surface microvilli with formation of blebs were particularly prominent and occurred within 2 min of exposure. Blebs regressed in some hepatocytes without evidence of cell death, when these cells were exposed to CCl4 under conditions promoting its evaporation. Disorganization of endoplasmic reticulum and mitochondrial injury were also prominent early findings. Rapid appearance of diffuse ultrastructural alterations in isolated hepatocytes exposed to CCl4 is consistent with nonspecific membrane injury induced by solvent effects.

Animals↗