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Biomedical subjects

J Dubuc

Publications and source records attributed to J Dubuc.

At least 19 recordsLinked to original sources
PubMed2006

Endoscopic screening for esophageal squamous-cell carcinoma in high-risk patients: a prospective study conducted in 62 French endoscopy centers.

BACKGROUND AND STUDY AIMS: The prevalence of esophageal squamous-cell carcinoma in high-risk patients and the advantages of systematic Lugol staining during esophagoscopy have not yet been evaluated in a large prospective study. In this study we aimed to assess the prevalence of this type of tumor in high-risk patients, to examine the role of Lugol staining in endoscopic screening for esophageal squamous-cell carcinoma, and to establish whether it is possible to identify a particularly high-risk group which would benefit from systematic screening. PATIENTS AND METHODS: A prospective study was undertaken in 62 endoscopy centers. A total of 1095 patients were enrolled, none of whom had any esophageal symptoms. These patients had presented with either a past history of or a recent head and neck or tracheobronchial squamous-cell carcinoma (group 1), with alcoholic chronic pancreatitis (group 2), with alcoholic cirrhosis (group 3), or were alcohol and tobacco addicts (group 4). The patients underwent a meticulous endoscopic examination of the esophagus, followed by Lugol staining. RESULTS: The prevalence of esophageal squamous-cell carcinoma was 3.2 %. The group 1 patients showed the highest prevalence of carcinoma (5.3 %) and the highest prevalence of dysplasia (4.5 %). Of the 35 carcinomas detected in the 1095 patients, seven (20 %) were early lesions, and 20 % were only detected after Lugol staining (P = 0.02). High-grade dysplasia was only observed in group 1 patients and two-thirds of these lesions were only diagnosed after Lugol staining. The overall prevalence of low-grade dysplasia was 2.4 %, and 77 % of these were detected only after Lugol staining (P < 0.001). CONCLUSIONS: Lugol dye staining increases the sensitivity of esophageal endoscopy for the detection of high-grade dysplasia and cancer. The prevalence of dysplasia and cancer reached 9.9 % in group 1, and we therefore believe that an endoscopic screening program could be justified for patients with head and neck or tracheobronchial cancer.

Adult↗
PubMed2002

Sarcoidosis-associated hepatitis C virus infection.

Although several reports of sarcoidosis have been reported in hepatitis C virus (HCV)-infected patients treated with interferon-alpha, this association has never been described in nontreated HCV patients. We report two cases of sarcoidosis associated with chronic hepatitis C infection. The patients developed multivisceral sarcoidosis (cutaneous, lungs, nodes) at two and at least six years after the presumed date of infection. One patient obtained remission of sarcoidosis with corticosteroid treatment but the other remained corticodependent. The levels of hepatic enzymes were not significantly modified throughout the course of corticosteroid therapy. In conclusion, these case reports suggest that HCV itself could induce a granulomatous reaction in chronic HCV-infected patients through the stimulation of the cellular immune system. It could be of interest to test for HCV infection all patients diagnosed with sarcoidosis and to watch over every treated or nontreated hepatitis C infected patient for the development of granulomatous lesions.

Adult↗
PubMed2001

[Sarcoidosis and comorbidity: retrospective study of 32 cases].

PURPOSE: A retrospective study was set up to investigate active pathologic processes associated with sarcoidosis diagnosed in 32 patients. METHODS: Eighteen patients had two identified granulomatous localizations (56%) and 14 patients had three localizations or more (27%). Comorbidity was noticed in nine patients (28% of cases). Sarcoidosis was associated with an infectious disease five times (hepatitis C virus [HCV] infection three times, including one case after recombinant interferon alpha therapy, and HIV and HCV co-infection two times). The association of sarcoidosis with a chronic immunologic inflammatory disease was noticed four times (lupus erythematosus two times, myasthenia and primary biliary cirrhosis). Finally, in two cases sarcoidosis was associated with a neoplasia (non-Hodgkin's lymphoma in a co-infected HIV-HCV patient, ovarian cystadenocarcinoma in another patient). Sarcoidosis preceded or revealed the comorbidity four times.

Adult↗
PubMed1990

Pharmacokinetics and disposition of the lipid-lowering drug acifran in normal subjects and in patients with renal failure.

The pharmacokinetics and metabolic fate of the antihyperlipidemic drug acifran were assessed after a single oral dose of the 14C-labeled drug to healthy male volunteers. Peak serum acifran and radioactivity concentrations were attained 1 to 2 hours after dosing, and the drug was eliminated with a half-life of 1.6 hours. Virtually all of the recovered dose was excreted in the urine. All of the serum and urinary radioactivity was caused by unconjugated acifran. In patients with moderate chronic renal failure, the binding of acifran to plasma proteins was decreased, and the plasma concentrations of total and unbound drug were greater than those of healthy subjects. Renal failure substantially reduced the plasma and renal clearance of total and particularly of unbound acifran, moderately reduced its volume of distribution, and increased its elimination half-life from 1.4 to 1.7 hours to 5.7 hours. The results show that acifran is very well absorbed, is rapidly eliminated, is excreted in the urine, and does not undergo any detectable biotransformation in healthy human subjects.

Adult↗
PubMed1986

Disposition and biotransformation of 14C-etodolac in man.

Four human subjects were given a capsule containing 200 mg of 14C-etodolac. At the peak (two hours after dosing), most of the radioactivity in serum was due to etodolac; subsequently, metabolites gradually appeared. The elimination half-life of etodolac from serum averaged six hours. Etodolac was greater than 99% bound to human serum proteins. An average of 73% of the dose was excreted in the urine and 14% in faeces within seven days, with 61% appearing in the urine during the first 24 h. Microbial transformation of etodolac was employed to biosynthesize sufficient amounts of two urinary metabolites to facilitate structure elucidation. Five metabolites, representing 65% of the radioactivity in urine collected 0-24 h after dosing (61% of the dose was excreted in urine within 24 h), were isolated and characterized by t.l.c., g.c., h.p.l.c., n.m.r (1H and 13C) and m.s. Most of the identified urinary components were conjugates of etodolac and three hydroxylated metabolites (6-hydroxyetodolac, 7-hydroxyetodolac and 8-(1-hydroxyethyl)etodolac). Two metabolites were identified as glucuronyl ester conjugates of etodolac and 7-hydroxyetodolac; the former represented about 20% of the urinary radioactivity. False positive tests for bilirubin in urine of patients treated with etodolac were found to be due to the two phenolic metabolites.

Acetates↗
PubMed1985

The effects of a new aldose reductase inhibitor (tolrestat) in galactosemic and diabetic rats.

Tolrestat(N-[[5-(trifluoromethyl)-6-methoxy-1-naphthalenyl] thioxomethyl]-N-methylglycine; AY-27,773; Alredase) is a potent, structurally novel inhibitor of aldose reductase (AR). In vitro, tolrestat inhibited in dose-dependent fashion the AR from bovine lenses (IC50, 3.5 X 10(-8) mol/L) and the formation of sorbitol in human RBC incubated with glucose (IC50, 3 X 10(-8) mol/L). Upon administration with the diet to rats made galactosemic or diabetic, tolrestat decreased, in a dose-related fashion, the accumulation of galactitol or sorbitol in the sciatic nerve and lens. The effectiveness of tolrestat depended upon the experimental conditions and tended to be higher in less severe galactosemia and after suitable pretreatment, particularly in galactosemic rats, resulting in ID50 of 5 mg/kg/d in the sciatic nerve and 12-15 mg/kg/d in the lens. Tolrestat also decreased, in dose-related manner, the RBC sorbitol levels in normal and in streptozotocin diabetic rats; in the latter, at less than 2 mg/kg/d, the RBC sorbitol was reduced to control levels.

Aldehyde Reductase↗
PubMed1984

Tolrestat kinetics.

The kinetics of tolrestat, a potent inhibitor of aldose reductase, were examined. Serum concentrations of tolrestat and of total 14C were measured after dosing normal subjects and subjects with diabetes with 14C-labeled tolrestat. In normal subjects, tolrestat was rapidly absorbed and disappearance from serum was biphasic. Distribution and elimination t 1/2s were approximately 2 and 10 to 12 hr, respectively, after single and multiple doses. Unchanged tolrestat accounted for the major portion of 14C in serum. Radioactivity was rapidly and completely excreted in urine and feces in an approximate ratio of 2:1. Findings were much the same in subjects with diabetes. In normal subjects, the kinetics of oral tolrestat were independent of dose in the 10 to 800 mg range. Repetitive dosing did not result in unexpected cumulation. Tolrestat was more than 99% bound to serum protein; it did not compete with warfarin for binding sites but was displaced to some extent by high concentrations of tolbutamide or salicylate.

Absorption↗
PubMed1983

Effect of AY-25,712 and other lipid-lowering agents on liver catalase and liver carnitine acetyltransferase in rats.

The effect of the hypolipidemic agent AY-25,712 on liver catalase and carnitine acetyltransferase was studied in rats. At 250 mg/kg/day for 2 or 4 weeks, i.e., at least 125 times the minimum effective hypolipidemic dose, AY-25,712 had no effect on liver weight or liver catalase. Liver catalase was elevated after a 2-week treatment with clofibrate (+ 30%), bezafibrate (+71%), and fenofibrate (+77%) at doses of 250 mg/kg/day, and with ciprofibrate (+111%) at 25 mg/kg/day. Gemfibrozil at 250 mg/kg/day for 4 weeks increased catalase by 86%. The relative increase in liver weight induced by these compounds showed a good correlation to increased catalase. Nicotinic acid (250 mg/kg/day for 2 weeks) did not alter liver weight or catalase. Clofibrate increased carnitine acetyltransferase by 176% while AY-25,712 had no effect. The results show that AY-25,712 and nicotinic acid did not induce changes in the livers of rats which are associated with treatment by various other hypolipidemic agents.

Acetyltransferases↗
PubMed1982

Evaluation of the lipid-lowering activity of AY-25,712 in rats.

The effect of AY-25,712 (2-methyl-2-phenyl-3(2H)-furanone-5-carboxylic acid) on serum lipids, hepatic lipogenesis and biliary cholesterol was investigated in male rats. Based on one-week treatment, the minimal effective dose of AY-25,712 which lowered serum triglycerides was 1 mg/kg/day, and LDL-cholesterol, 5 mg/kg/day. Nicotinic acid produced a similar lipid-lowering profile albeit at 5 times higher doses. AY-25,712 at doses of 2 mg/kg/day and higher significantly increased the ratio of HDL to total cholesterol. Unlike clofibrate, AY-25,712 did not increase liver weight or liver mitochondrial alpha-glycerophosphate dehydrogenase, nor increase biliary cholesterol levels in rats fed a diet containing 2% cholesterol and 0.5% cholic acid. AY-25,712 lowered serum cholesterol, triglycerides and phospholipids in rats rendered hyperlipidemic with Triton WR-1339 and decreased the elevated serum triglycerides in streptozotocin-diabetic rats. [14C]Acetate incorporation into cholesterol by liver homogenate was suppressed in rats given AY-25,712 p.o. for 1 week. The results show that AY-25,712 is a potent LDL-cholesterol- and triglyceride-lowering agent in rats, and that its lipid-lowering profile differs from that of clofibrate but resembles that of nicotinic acid.

Animals↗
PubMed1982

Effect of AY-25,712 on fatty acid metabolism in rats.

The effect of AY-25,712 [2-methyl-2-phenyl-3(2H)-furanone-5-carboxylic acid] on various aspects of free fatty acid (FFA) and triglyceride metabolism was studied in male rats. Serum triglycerides were lowered by a single oral dose of AY-25,712 or nicotinic acid, but not of clofibrate. Unlike with clofibrate, when AY-25,712 or nicotinic acid was given in the diet, serum triglycerides were not affected. In vitro, both AY-25,712 and nicotinic acid suppressed the theophylline-induced FFA release by epididymal fat pads, but had no effect on lipolysis induced by norepinephrine. Both AY-25,712 and nicotinic acid enhanced the activity of adipose tissue lipoprotein lipase. The initial decrease in plasma FFA and triglycerides, and in liver triglycerides after a single oral dose of nicotinic acid was followed by a rebound to levels which, at later time intervals, wee significantly higher than in controls. AY-25,712 was more potent than nicotinic acid in lowering plasma FFA and triglycerides as well as liver triglycerides, but produced no such rebound effect. The data show that, except for the absence of this rebound effect, the mode of action of AY-25,712 in rats resembles that of nicotinic acid and differs from that of clofibrate.

Adipose Tissue↗
PubMed1977

Effect of tibric acid on hepatic cholesterol synthesis in rats.

Male albino rats were administered various oral doses of tibric acid daily for 1 week. Serum cholesterol and triglyceride levels were reduced, but total liver content of cholesterol, phospholipids, and triglycerides was increased. Tibric acid treatment suppressed the incorporation of both [14C] acetate and [3H] mevalonate into cholesterol by liver homogenates.

Acetates↗