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Biomedical subjects

P Couzigou

Publications and source records attributed to P Couzigou.

At least 19 recordsLinked to original sources

A comparison of three interferon alfa-2b regimens for the long-term treatment of chronic non-A, non-B hepatitis. Multicenter Study Group.

BACKGROUND: We studied the effects of long-term treatment with interferon on histologic features of the liver and serum alanine aminotransferase concentrations in patients with chronic non-A, non-B hepatitis. METHODS: Consecutive patients who met the inclusion criteria were enrolled in the study. The diagnosis of chronic non-A, non-B hepatitis was established on the basis of the liver-biopsy findings and an abnormal serum alanine aminotransferase value (greater than 1.5 times the normal value) for at least one year. All patients were treated for six months with 3 million units of interferon alfa-2b given subcutaneously three times a week and were then randomly assigned to the same treatment for an additional 12 months (group 1), a regimen of 1 million units three times a week for 12 months (group 2), or no further treatment (group 3). Patients in group 3 who had elevated serum alanine aminotransferase concentrations for three consecutive months underwent the initial regimen once again. Follow-up continued for two years after the discontinuation of treatment. Histologic improvement was defined as a decrease of at least one grade in the score for necroinflammatory activity (0, no activity; 1, mild; 2, moderate; or 3, severe) between the first liver biopsy and a biopsy performed at 18 months. RESULTS: Of the 329 patients initially treated, 303 were randomized: 103 to group 1, 101 to group 2, and 99 to group 3. Of the 286 patients tested, 252 (88.1 percent) had antibodies to hepatitis C virus. In an intention-to-treat analysis, 46 of the patients in group 1 (44.7 percent) had normal serum alanine aminotransferase values at 18 months, as compared with 27 of the patients in group 2 (26.7 percent, P = 0.008) and 30 of those in group 3 (30.3 percent, P = 0.04). Between 19 and 42 months, 23 of the patients in group 1 (22.3 percent) continued to have normal serum alanine aminotransferase values (measured every six months), as compared with 10 of the patients in group 2 (9.9 percent, P = 0.02) and 8 of those in group 3 (8.1 percent, P = 0.005). Among the 176 patients with repeated liver biopsies at 18 months, more patients in group 1 had improved histologic-activity scores (69.6 percent) than in group 2 (47.6 percent, P = 0.02) or group 3 (38.6 percent, P < 0.001). CONCLUSIONS: Among patients with chronic non-A, non-B hepatitis, a regimen of 3 million units of interferon alfa-2b given three times a week for 18 months produced better histologic findings and serum alanine aminotransferase values than regimens involving a lower dose or a shorter duration of treatment.

Alanine Transaminase

[Skin manifestations related to hepatitis C viruses].

The hepatitis C virus causes both hepatic and extrahepatic disorders, particularly as regards dermatology. The link between essential mixed cryoglobulinemias and the C virus infection has been clearly evidenced., whereas its frequency seems low in other systemic vasculitis such as polyarteritis nodosa. Similarly, the link between C virus hepatopathy and porphyria cutanea tarda is now proven. Lichen planus is also described as being associated with this virus, but further epidemiological studies are required to determine the exact prevalence of lichen in C virus hepatopathy cases. Finally, various cutaneous disorders, such as urticaria, erythema multiforme, dermo-hypodermitis, etc, occasionally arise during acute or chronic hepatitis C.

Cryoglobulinemia

[Quality of psychomotor recovery after colonoscopy under general anesthesia using propofol. Value of tests of awakening].

Achieving colonoscopy under general anaesthesia entails the problem of ambulatory-care anaesthesia, in particular because perception of patient's recovery determines to some extent the length of monitoring following colonoscopy. The aims of the study was to assess the quality of patient's recovery after a colonoscopy under general anaesthesia while using propofol, by means of psychomotor-tests. METHODS--Colonoscopy was performed in 40 patients according to the following anaesthetic protocol: induction: propofol 2 mg/kg, continuous support: propofol 10 mg/kg/h i.v. with a 50 mg bolus in case of insufficient sedation; series of 3 psychomotor-tests were performed the day before and 1 hour, 3 hours and 6 hours after colonoscopy. The 3 psychomotor-tests studied: coordination (Newman test), time-space orientation and short-term memory. RESULTS--Forty patients, 25 females and 15 males, underwent colonoscopy with general anaesthesia for an average time-period of 22 +/- 11 min. The mean dose of propofol used was 286 +/- 102 mg. Awakening was complete in all patients, according to physical criteria such as consciousness and cardiovascular status, 20 min after receiving colonoscopy. The average psychomotor-tests results over time were (as percentages of original values) (*P < 10(-3); **P < 0.05): [table: see text] At 6 hours, 35 patients (87.5%) had recovered to their original performance and at 3 hours, 30 patients (75%) retained 90% their former state as measured with 3 psychomotor-tests. Neither by age or sex nor by propofol doses used or length or anaesthesia, the study population differed significantly. CONCLUSION--Three hours after colonoscopy under general anaesthesia using propofol, 30 patients (75%) had recovered at least 90% to their initial performances. Newman test was the most disturbed but there was no predictive factor for the quality of recovery. Psychomotor-tests may be useful before authorizing early discharge after colonoscopy under general anaesthesia but other recommendations about conditions of discharge after sedation must be also implemented.

Anesthesia Recovery Period

Prevention of relapse in patients with chronic non-A, non-B/C hepatitis who respond to alpha-interferon. A controlled multicenter trial of low-dose maintenance therapy. Groupe d'Etude Multicentrique de l'Interféron dans les Hépatites.

We tested the efficacy of maintenance treatment with alpha-2a interferon, 1 megaunit thrice weekly for 6 months, in preventing relapse of non-A, non-B/C hepatitis in remission after treatment with alpha interferon given thrice weekly according to the following dose schedule: 3 megaunits for 3 months, 2 megaunits for 2 months and 1 megaunit for 1 month. Fifty-three patients with hepatitis C in remission were randomly allocated to a treatment group (n = 26) or a control group (n = 27). A relapse (aminotransferase activity > 1.5 times the upper limit of normal) occurred in 46% of the controls and 35% of the treated patients (NS). Maintenance treatment had no significant influence on histopathologic changes evaluated by three independent observers: in both groups the overall score for histologic lesions improved between the initiation of interferon therapy and the end of the study. We conclude that relapses in patients with non-A, non-B/C hepatitis in remission after treatment with alpha interferon at tapering doses are not prevented by maintenance therapy with low-dose alpha interferon. Journal of Hepatology.

Alanine Transaminase

Genetic polymorphism of apolipoprotein E in Caucasian alcoholic cirrhotics.

Steatosis is the most common although inconstant hepatic lesion induced by chronic alcohol consumption. Alcoholic cirrhosis is found in only 20 to 30% of chronic alcohol misusers, which points to the influence of both environmental and genetic factors. Apolipoprotein E (apo E) presents an important polymorphism with three common alleles, epsilon 4, epsilon 3 and epsilon 2. Its modulation role on triglyceride-rich lipoproteins and cholesterol-containing lipoproteins is linked with its interaction with cellular specific receptors. This work aims at studying a possible correlation between apo E polymorphism and alcoholic cirrhosis. The three common alleles were identified by enzymatic amplification (PCR) of genomic DNA from blood samples and analysis of restriction profiles. The distribution of alleles and genotypes was performed in 35 Caucasian cirrhotic patients (medium age 57 years) and compared with the usual distribution of apo E phenotypes in European Caucasian populations. The results show lower epsilon 4 and epsilon 2 allele frequencies and higher epsilon 3 allele frequency in Caucasian alcoholic cirrhotics.

Adult

Chromosome analysis of adenomatous polyps of the colon: possible existence of two differently evolving cytogenetic groups.

A chromosomal study of 42 colonic adenomatous polyps was performed using a technique of direct chromosome analysis derived from the prenatal procedure for diagnosing chromosomal alterations from chorionic villi sampling. Abnormal karyotypes were found in 22 cases. Trisomy 7, the most frequently found alteration, was found in 13 cases, followed by trisomy 13 (nine cases). Monosomy 18 was observed in two cases; in one of these, that of a polyp which had degenerated into an intra-mucosal adenocarcinoma, it was associated with 17p monosomy. Interestingly, these two types of alterations (trisomy 7 versus 18 and 17p monosomy) were not found together in the same lesion. This suggests that there could be two distinct chromosomal behaviors which might be related to the two cytogenetic groups described for colorectal adenocarcinoma. However, the respective frequencies of such cytogenetic groups varied inversely between adenomas and adenocarcinomas, thus suggesting that they evolve differently.

Adult

Detection of HCV-RNA in saliva of patients with chronic hepatitis C.

Previous studies have provided conflicting results on the presence of hepatitis C virus-RNA in saliva. In this study, 23 (62%) of 37 patients tested positive for hepatitis C virus-RNA in saliva, using polymerase chain reaction analysis. A slightly greater proportion had a sporadic rather than a parenteral origin of chronic hepatitis C. These results provide a biological basis for saliva as a possible source of hepatitis C virus (HCV) infection, but do not necessarily imply transmission by this route.

Adult

Polymorphism of alcohol dehydrogenase, alcohol and aldehyde dehydrogenase activities: implication in alcoholic cirrhosis in white patients. The French Group for Research on Alcohol and Liver.

Two types of factors can theoretically modulate alcohol metabolism toward increased acetaldehyde production. These factors are the following: (a) individual, genetically determined isoenzymes with distinct catalytic properties, and (b) modifications of enzyme activity induced by alcohol itself or liver damage. To investigate the respective roles of these factors in white individuals, we studied the alcohol dehydrogenase phenotype, together with liver alcohol dehydrogenase and aldehyde dehydrogenase activities, in 161 patients. Patients with alcoholic cirrhosis (n = 31) were compared with three types of controls: patients with nonalcoholic cirrhosis (n = 25) and excessive (n = 62) and moderate drinkers (n = 43) without liver disease. No association between alcohol dehydrogenase-3 phenotype and alcoholic cirrhosis was found. The prevalence of atypical alcohol dehydrogenase in the four groups was less than 1%. Patients with cirrhosis, regardless of its cause, had significantly lower alcohol dehydrogenase activity than the patients without cirrhosis (p less than 0.05 and p less than 0.01 vs. excessive and moderate drinkers, respectively). Among the noncirrhotic patients, alcohol dehydrogenase activity was significantly lower in the excessive drinkers than in the moderate drinkers (p less than 0.001). Aldehyde dehydrogenase activity was not different between cirrhosis-free excessive and moderate drinkers; in contrast, compared with these two groups, it was significantly lower in the two cirrhosis groups (p less than 0.01). These results suggest that no phenotypic pattern of alcohol dehydrogenase-3 associated with alcoholic cirrhosis in white patients exists, that liver alcohol dehydrogenase activity falls as a consequence of both alcohol abuse and cirrhosis and that liver aldehyde dehydrogenase activity is unaffected by alcohol abuse and only falls after the onset of cirrhosis.

Adult

Pharmacokinetics of famotidine in patients with cirrhosis and ascites.

The pharmacokinetics of famotidine has been investigated in ascitic cirrhotic patients. 10 decompensated cirrhotic patients were studied (9m, 1f), who had normal renal function, and six healthy control subjects (4m, 2f), matched for age, sex and weight. Each subject received on two occasions, at least four days apart, a single oral (40 mg) or intravenous dose (20 mg) of famotidine, at 21.00 h in a randomised manner. Serial blood samples were collected and famotidine in plasma was determined by a HPLC/UV method. Plasma data were subjected to non compartmental pharmacokinetic analysis. There were no statistically significant differences in pharmacokinetic parameters between the two groups after either the intravenous or oral administration of famotidine. The findings suggest that the dose of famotidine may not require any adjustment in ascitic patients without renal failure.

Administration, Oral

Polymorphism of class I alcohol dehydrogenase in French, Vietnamese and Niger populations: genotyping by PCR amplification and RFLP analysis on dried blood spots.

The polymorphism of human alcohol dehydrogenase (ADH) can contribute to the explanation of the important ethnic differences towards alcohol metabolism. Its assessment at the genomic DNA level with a procedure, excluding labelled probes, consisting of PCR (Polymerase chain reaction) amplification on dried blood spots and analysis of allele-specific RFLP (Restriction fragment length polymorphism) profiles, is well adapted to extensive studies in population samples. It can emphasize the importance of ADH as a genetic marker of population. Three ethnic groups (French Caucasians, Vietnamese Orientals, Black Africans from Niger) were studied. ADH2 and ADH3 genotypes were in equilibrium according to the Hardy-Weinberg law. Important differences were noted in the distribution of ADH2 and ADH3 alleles.

Alcohol Dehydrogenase

[Possible sexual transmission of hepatitis C virus].

The development of hepatitis C virus (HCV) serology has made it possible to identify high-risk populations. The predominant mode of contamination is parenteral, but the relative frequency of the so-called sporadic hepatitis C cannot be explained in this way, and this raises the question of possible sexual contamination. The risk of HCV being transmitted by sexual intercourse has been studied in 30 couples, each with one infected partner. Among the 30 HCV seropositive subjects, 18 were followed up for chronic hepatitis and 2 for haemophilia; 10 were recruited in sessions of blood donation. The other 30 partners were tested for HCV seropositivity and investigated for other possible risk factors by means of a questionnaire. Three of them had antibodies to HCV, but only one, whose partner had chronic hepatitis, showed no other source of contamination. The prevalence of HCV positivity was 3.3 percent overall and 5.5 percent in the chronic hepatitis group. Thus, the risk of HCV heterosexual contamination is low when compared with that of the other sexually transmitted diseases. However, the prevalence of HCV in this population seems to be 5 to 10 times higher on average than in the general population.

Adult