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Biomedical subjects

B Combes

Publications and source records attributed to B Combes.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1983

Biliary excretion of infused conjugated sulfobromophthalein in sheep heterozygote for the transport defect present in mutant Corriedale sheep.

Biliary excretion of dye was measured in 2 clinically normal and 2 heterozygote Corriedale sheep (the mutant Corriedale is characterized by depressed biliary transport of conjugated sulfobromophthalein (SBP) compounds) during infusion of the preformed glutathione conjugate of SBP. Maximal rates of excretion of conjugated SBP compounds in bile were comparable in heterozygote Corriedale and clinically normal sheep. These 2 heterozygote sheep do not express the biliary transport defect observed in mutant Corriedale sheep during SBP-glutathione infusion.

Animals↗
PubMed1982

Effect of diethyl maleate on the biliary excretion rate of infused sulfobromophthalein-glutathione.

Diethyl maleate (DEM) was given intraperitoneally to rats in a dose (4.3 mmoles/kg) known to markedly decrease glutathione levels in liver. DEM induced a choleresis previously shown to be due to the osmotic activity of DEM conjugates (DEM-glutathione and subsequent metabolic products) excreted into bile. Coincident with the choleresis, the biliary excretory Tm for the infused glutathione conjugate of sulfobromophthalein (BSP-GSH) was depressed significantly. The data are interpreted as indicating that DEM-GSH conjugates compete with BSP-GSH conjugates for a canalicular carrier mechanism.

Animals↗
PubMed1981

A prospective trial of steroid therapy in severe viral hepatitis. The prognostic significance of bridging necrosis.

A prospective, double-blinded, randomized trial of corticosteroid therapy in patients with severe acute viral hepatitis has been conducted. At the same time, we have examined the prognostic significance of the presence of bridging necrosis in liver biopsies obtained from such patients as well as the predictive value of certain serologic markers. Forty-two of the 77 patients admitted to the trial were shown to have bridging necrosis on their initial biopsies. Two patients progressed to death with massive hepatic necrosis, while 5 patients developed chronic liver disease. A complicated course could not be predicted by the initial biopsy findings nor by any of the serologic markers assessed. We could not identify any clinical or epidemiologic features with prognostic impact. No advantage was demonstrated to be associated with the use of corticosteroids early in the course of severe viral hepatitis.

Adolescent↗
PubMed1980

Beneficial effect of cholestyramine in sclerosing cholangitis.

Cholestyramine exerted a beneficial effect on the course of a patient with sclerosing cholangitis associated with ulcerative proctitis. Over a 6.5-yr period, discontinuation of cholestyramine resulted in episodes of RUQ pain and/or appearance of abnormalities in liver tests. Readministration of the resin was followed by disappearance of symptoms and normalization of test resuls. The mechanism of the beneficial effect of cholestyramine was not elucidated.

Adolescent↗
PubMed1979

Apparent volume of the biliary tree in the dog.

The apparent volume of the biliary tree (ABV) in the dog was determined by measuring the mean biliary transit time of injected [14C]taurocholate ([14C]TC). After bolus injection of [14C]TC, entry of bile salt into the lumen of the biliary tree is signaled by an increase in bile flow. The volume of bile collected at the common duct from onset of choleresis until maximal concentration of 14C radioactivity is reached in bile minus the calculated quantity of bile that contains radioactivity and the cannula volume yields a value for the volume of the biliary tree present just prior to injection of [14C]TC. The mean value for ABV in 19 dogs was 2.49 +/- 0.65 microL/g liver (mean +/- SD).

Animals↗
PubMed1979

Etiology of liver disease in renal-transplant patients.

The etiology of 72 episodes of liver disease that developed in 62 of 162 renal-transplant recipients was evaluated. Infection with hepatitis B virus was a minor problem, and none of our patients had evidence of infection with hepatitis A. Cytomegalovirus infection was ubiquitous in the population and probably accounted for many episodes of acute liver disease. This agent's role in causing chronic hepatitis is less secure. Infections with other viruses including Epstein-Barr virus, adenovirus, and the herpes viruses were only rarely associated with hepatic disease. Azathioprine was responsible for some episodes of acute cholestasis but could not be incriminated as a direct cause of chronic disease. A cause could be identified for the majority of episodes of acute hepatic dysfunction, but the cause of most of the chronic hepatitis remains undetermined. It is likely that infection with non-A, non-B hepatitis virus accounts for much of this serious, often fatal, complication of renal transplantation.

Antibodies, Viral↗
PubMed1978

Urinary excretion of dye in dogs infused with BSP or its glutathione conjugate.

Renal clearance of BSP compounds was investigated in dogs during infusion of sulfobromophthalein (BSP) or its glutathione conjugate (BSP-GSH). Conjugated BSP compounds are more readily excreted into urine than unconjugated BSP. Dye clearance into urine was much less than simultaneously measured inulin clearance. This suggests that protein binding of BSP compounds significantly retards the glomerular filtration of the dye. BSP was found to bind more avidly to albumin than BSP-GSH. The ratio of dye clearance to inulin clearance remained relatively constant over a broad range of plasma concentrations of dye. The data support but do not prove glomerular filtration of non-protein-bound dye as the major mechanism accounting of urinary elimination of BSP compounds in the dog.

Animals↗
PubMed1978

Erythritol and mannitol clearances with taurocholate and secretin-induced cholereses.

The biliary clearances of [14C]erythritol (Cery) and [3H]mannitol (Cmann) were measured simultaneously in dogs during cholereses induced by sodium taurocholate and by secretin. Cery increased equally with the increase in bile flow induced by taurocholate, whereas mannitol entry into bile was partially restricted; deltaCery/deltabile flow averaged 0.96; deltaCmann/deltaCery averaged 0.81. Values for erythritol clearance exceeded bile flow by a constant volume over a wide range of bile flows, a result that suggests distal reabsorption of a fixed amount of fluid, independent of canalicular bile production. During secretin-induced choleresis both Cery and Cmann accompanied 30-40% of the increase in bile flow, and the ratio of Cmann/Cery was 1.02. Thus the secretin-responsive region is permeable to both erythritol and mannitol. This affects the extent to which measured erythritol clearance accurately reflects canalicular bile formation; Cery may underestimate or overestimate canalicular bile flow. The electrolyte composition of bile remained relatively constant over a broad range of bile flows although the characteristics of taurocholate- and secretin-induced biles differed from each other. Taurocholate-stimulated bile was virtually isotonic. Secretin-induced bile had a high total concentration of electrolyte (mean concentration 367 meq/liter) rich in chloride and bicarbonate and was hypertonic.

Animals↗
PubMed1978

Characterization of SC2644-induced choleresis in the dog. Evidence for canalicular bicarbonate secretion.

The biliary clearances of [14C]erythritol (Cery) and [3H]mannitol (Cmann) were measured simultaneously in dogs, first during choleresis induced by varying doses of sodium taurocholate and then by SC2644. Cery increased equally with the increases in bile flow induced by both compounds. Mannitol entry into bile, however, was partially restricted; deltaCmann/deltabile flow averaged 0.66 and 0.68 for taurocholate- and SC2644-induced flows, respectively. These findings suggest a common canalicular site of origin of the increased bile flow. Electrolyte composition was quite different in the increments, however. The bicarbonate concentration in the SC2644-induced increment of bile (65.8 microEq/ml) was three times higher than that associated with bile stimulated by taurocholate. SC2644- and taurocholate-induced biles were virtually isosmotic. These results in concert with other observations suggest a canalicular mechanism for bicarbonate entry into the biliary tree. Stimulation by SC2644 of ductal chloride bicarbonate exchange cannot be excluded, however.

Animals↗
PubMed1978

Choleresis associated with metabolism and biliary excretion of diethyl maleate in the rat and dog.

Diethyl maleate (DEM) induces a choleresis in the rat and dog that appears to be canalicular in origin (bile flow and erythritol clearance increase equally) and occurs in the absence of an increase in bile salt excretion. Increased bile flow is probably accounted for by the osmotic activity of DEM compounds excreted into bile. These compounds represent the glutathione conjugate of DEM (DEM-GSH) and its subsequent metabolic products. Conjugation of DEM largely accounts for the depletion of hepatic GSH.

Animals↗
PubMed1977

Hepatitis and pregnancy.

The maternal and fetal outcomes of 50 pregnancies complicated by acute viral hepatitis were examined. Twenty (40%) cases were due to type B hepatitis virus. The clinical course of the maternal hepatitis was unaffected by the pregnant state. Maternal hepatitis (type B or nontype B) had no effect on the incidence of congenital malformations, stillbirths, abortions, or intrauterine malnutrition; it did increase the incidence of prematurity (type B 31.6%; nontype B 25%; overall 27.6%) over that seen in the general delivery population (10 to 11%). Eight mothers acquired acute type B hepatitis during the third trimester; two of their infants (25%) were found to be chronic asymptomatic carriers of hepatitis B surface antigen and to have mild, persistent elevations of SGOT for up to 45 months.

Carrier State↗
PubMed1977

Serum gamma-glutamyl transpeptidase activity in viral hepatitis: suppression in pregnancy and by birth control pills.

gamma-Glutamyl transpeptidase (GGT) activity in serum was increased in the majority of women with viral hepatitis occurring in the first half of pregnancy. By contrast, GGT activity was abnormal less frequently and the mean value was relatively depressed, even though hepatitis was as severe, in the second half of gestation. Mean GGT activity was also lower, and abnormal values were less frequent, in nonpregnant women with viral hepatitis who were taking birth control pills (BCP). Depressed GGT is not attributable to an inhibitor in serum in women in late pregnancy or taking BCP. The data suggest that estrogen and/or progestational compounds affect liver such that less GGT is released into blood with acute hepatocellular injury. In addition, hyperbilirubinemia was found to be associated with depressed serum GGT activity, and bilirubin added to serum in vitro interfered with measured activity of the enzyme.

Bilirubin↗