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Biomedical subjects

J C Chaput

Publications and source records attributed to J C Chaput.

At least 73 records · Page 4Linked to original sources

Pharmacokinetics of zidovudine in patients with liver cirrhosis.

The pharmacokinetics of zidovudine (azidothymidine, AZT) was investigated after oral administration (200 mg) in 14 human immunodeficiency virus seronegative patients with liver cirrhosis. They were divided in three groups according to the severity of the liver disease quantitated by the Child-Pugh score. Plasma and urine concentrations of zidovudine and its glucuronidated metabolite (GAZT) were measured simultaneously by HPLC assay. Findings were compared with those previously measured in six healthy volunteers. As a consequence of a marked drop in oral clearance (10 +/- 4 versus 38 +/- 15 ml/min/kg), zidovudine concentrations, half-life, and mean residence time were increased in patients with cirrhosis. No difference could be established between the three groups. The reason for such a decrease in oral clearance of zidovudine was the reduction in the GAZT formation clearance (236 +/- 73 versus 1540 +/- 540 ml/min); this led to a decrease in the AUC ratio of GAZT and zidovudine (1.3 +/- 0.6 versus 4.6 +/- 0.7), which was directly related to the severity of the cirrhosis. In patients, as in volunteers, formation of GAZT rate limits its elimination. To avoid important cumulation of zidovudine after repeated dosing in patients with acquired immunodeficiency syndrome who have hepatic impairment, a dosage adjustment could be proposed.

Adult↗

Serum apolipoprotein A-I in alcoholic patients with chronic calcifying pancreatitis.

Serum apolipoprotein A-I measurement was compared in alcoholic patients according to presence or absence of chronic pancreatitis and liver fibrosis. Among alcoholic patients without liver disease, apolipoprotein A-I was significantly lower in patients with chronic pancreatitis (157 +/- 70 mg/dl) than in patients without pancreatitis (209 +/- 74 mg/dl, p less than 0.001). In cirrhotic patients, apolipoprotein A-I was lower in patients with chronic pancreatitis (82 +/- 35 mg/dl) than in patients without pancreatitis (102 +/- 45 mg/dl), but this difference was not significant. The decrease of serum apolipoprotein A-I was independent of nutritional parameters whether or not there was cirrhosis. Immunohistochemical study of pancreatic samples with chronic pancreatitis showed that apolipoprotein A-I was located in the pancreatic fibrosis whereas lobules were unstained. This study suggests that apolipoprotein A-I is trapped by the pancreatic extracellular matrix and that this sequestration might explain, in part, the decrease of the serum apolipoprotein A-I.

Adult↗

Diagnostic value of serum gamma-glutamyl-transferase activity and mean corpuscular volume in alcoholic patients with or without cirrhosis.

In an attempt to assess the diagnostic values of serum gamma-glutamyltransferase (GGT) and mean corpuscular volume (MCV) variations as markers of liver disease and of abstinence in alcoholic patients, we compared 174 patients with alcoholic cirrhosis, 175 with noncirrhotic alcoholic liver disease and 67 patients with nonalcoholic cirrhosis. GGT and MCV values were checked three times, the day of admission, 7 days later, and on the last sample available during follow-up (1 to 12 months), and were compared according to the liver disease and abstinence. A decrease of GGT activity during the 1st week of hospitalization was noted in alcoholics with (-9 IU/liter) or without (-13 IU/liter) cirrhosis and not in nonalcoholic cirrhosis (+8 IU/liter), without MCV variations. During follow-up, median GGT activity was strikingly different in abstinent patients with (27 IU/liter) or without (21 IU/liter) cirrhosis and in nonabstinent patients (99 IU/liter and 123 IU/liter, respectively) (p less than 0.001). MCV decrease was noted in alcoholics whatever their abstinence or not, contrasting with the absence of decrease in nonalcoholic patients. For the diagnosis of alcoholism in cirrhotic patients, the positive predictive value (PPV) of a GGT or a MCV decrease during the 1st week of hospitalization was 0.82 and 0.78, respectively, and the negative predictive value (NPV) was 0.33 and 0.70, respectively. For abstinence during follow-up, the PPV of a GGT activity less than 50 IU/liter was 0.92 and the NPV was 0.65.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗

[Acute tuberculous pancreatitis in a patient with acquired immunodeficiency syndrome].

The authors report a case of tuberculous pancreatitis in a 29 year old Zairan man. Serum antibodies against HIV were positive. T-lymphocyte analysis revealed 18/mm3 OKT4 with an OKT4/OKT8 ratio of 0.43. The initial examination suggested severe acute pancreatitis. Only the postmortem histopathological analysis revealed tuberculous pancreatitis, showing several miliary lesions with caseous necrosis and acid fast bacili (Ziehl stain). Subsequently, cultures (sputum, bronchoalveolar lavage, pleural effusion, ascitis) of bacili identified Mycobacterium tuberculosis. Tuberculous pancreatitis should be considered in subjects with acute pancreatitis according to the epidemiological context, once the most frequent causes of pancreatitis have been eliminated.

Acquired Immunodeficiency Syndrome↗

Endoscopic laser therapy for duodenal villous adenoma.

A 72-year-old woman had a 20-mm supraampullary villoglandular adenoma with a focal carcinoma in situ. The neurological status of the patient did not allow any major surgical procedure. Therefore laser therapy was performed using the Nd:YAG laser. Six laser sessions were necessary to destroy the whole adenoma. After 30 months of follow-up, there was neither endoscopic nor histologic recurrence. The laser therapy should be therefore considered in treating large sessile duodenal villous adenoma occurring in inoperable patients. However, a repeated endoscopic surveillance must be performed.

Adenoma↗

Apolipoprotein AI is a serum and tissue marker of liver fibrosis in alcoholic patients.

The aim of this study was to assess the specific correlation of apolipoprotein-AI to hepatic fibrosis in alcoholic patients. Four hundred eighty two patients were prospectively included with serum measurement of apolipoprotein-AI within 10 days before liver biopsy. Pathologic features were semiquantitatively assessed by two observers. In 28 patients liver biopsy was used for histomorphometric assessment of fibrosis and immunohistochemical labeling of apolipoprotein-AI. Serum apolipoprotein-AI was negatively correlated to semiquantitative score of fibrosis (r = -0.50; p less than 0.001), independently of the scores of steatosis and alcoholic hepatitis (r = -0.44; p less than 0.001) and of the value of serum albumin, bilirubin, and prothrombin time (r = -0.22; p less than 0.001) and independently of the nutritional parameters (r = -0.29; p less than 0.009). The mean value of apolipoprotein-AI decreased according to the grade of fibrosis from 220 +/- 6 mg/dl (mean +/- SEM) to 110 +/- 8 mg/dl. Serum apolipoprotein-AI was negatively correlated to the percentage of fibrosis (r = -0.70; p less than 0.001) in the biopsies morphometrically assessed. The labeling was superimposed to the extracellular matrix. In conclusion, this study shows that decrease of apolipoprotein-AI is a serum and tissue marker of liver fibrosis independently of steatosis, alcoholic hepatitis, liver function tests, and nutritional parameters.

Apolipoprotein A-I↗

Perisinusoidal cells (Ito-cells) enlargement in a family with myotonic dystrophy.

Two cases are reported, a daughter and her mother who both have myotonic dystrophy with abnormalities of liver function tests and an important perisinusoidal cell enlargement without other pathologic features. In both cases, the myotonic dystrophy was clinically obvious and confirmed by electromyography. No other causes of perisinusoidal cell enlargement were found including vitamin A intake, psoriasis, viral disease or alcoholism. These observations suggest a genetic linkage and that serum test abnormalities could be associated with a perisinusoidal cell change.

Adolescent↗

[Double-blind controlled study of the efficacy of nifuroxazide versus placebo in the treatment of acute diarrhea in adults].

In a double-blind, controlled randomized trial, 88 adult patients with acute diarrhea (more than three watery stools per day) received either 400 mg of nifuroxazide twice daily or placebo for 5 days. The mean duration of diarrhea in the nifuroxazide group was 2.09 days versus 3.26 days in the placebo group (p less than 0.004). The number of bowel movements per day diminished and mucus disappeared more quickly in patients treated by nifuroxazide than in patients of the placebo group. Nifuroxazide was well tolerated and no side effects were observed. Nifuroxazide is an effective therapy for acute diarrhea and can be prescribed from the onset of diarrhea without waiting for stool culture results which can be late or negative.

Acute Disease↗

Nadolol for prophylaxis of gastrointestinal bleeding in patients with cirrhosis. A randomized trial.

This controlled trial was designed to evaluate the prophylactic effect of nadolol on gastrointestinal bleeding in cirrhotic patients with large oesophageal varices who had never bled. Nadolol or placebo was given randomly to two groups of 53 patients. The percentage of patients free of gastrointestinal bleeding 1 year after inclusion in the study was 83 +/- 6% (mean +/- S.D.) in the nadolol group and 80 +/- 6% in the placebo group. In the nadolol and placebo groups, 40 and 47 patients, respectively, were compliant, i.e., took nadolol or placebo continuously. The percentage of patients who were free of bleeding 1 year after inclusion was 97 +/- 3% in the subgroup of compliant nadolol patients. This percentage was significantly higher than that of patients who were free of bleeding in the placebo group (P less than 0.03) as well as in the subgroup of compliant placebo patients (77 +/- 6%; P less than 0.02). We concluded that, although there was no overall significant effect of nadolol on the risk of bleeding in cirrhotic patients in good condition with large oesophageal varices, this study suggests that nadolol reduced the risk of bleeding in compliant patients.

Clinical Trials as Topic↗

Observer variation in assessment of liver biopsies of alcoholic patients.

The aim was to construct a questionnaire analyzing pathological features possibly present in alcoholic liver disease, to assess its interobserver variation and to determine the influence of technical data on this variation. A total of 764 inpatients drinking 90 g (median) of pure alcohol per day for 25 years was observed; 402 patients were excluded because of associated nonalcoholic disease, refusal or contraindication to biopsy, leaving 362 patients included. Two pathologists independently analyzed each biopsy and completed a questionnaire including 41 items. Coefficient of concordance between observers was evaluated with the kappa statistic (k). The prevalence of 14 lesions was low, equal to or under 10%, leading to a nonsignificant concordance. For the 27 remaining features, two had an almost perfect degree of concordance (k greater than 0.81): presence of hepatocellular carcinoma and cirrhosis. Three had a substantial coefficient of concordance (k greater than 0.61): fibrous septa, size of cirrhotic nodules, and liver cell regeneration. Nine had a moderate (k greater than 0.41), 11 a fair (k greater than 0.21), and two a slight (k less than 0.21) coefficient of concordance. In terms of final diagnosis of alcoholic liver disease the concordance was substantial for cirrhosis with acute alcoholic hepatitis (k = 0.77), cirrhosis without alcoholic hepatitis (k = 0.75), acute alcoholic hepatitis without cirrhosis (k = 0.65) and normal liver (k = 0.64). Concordance was moderate for steatosis (k = 0.47) and slight for fibrosis alone (k = 0.16).(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗