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Biomedical subjects

C Raffanel

Publications and source records attributed to C Raffanel.

At least 19 recordsLinked to original sources

[Highly elevated alphafetoprotein and hepatic cirrhosis. It is not always hepatocarcinoma].

BACKGROUND: Alphafetoprotein assay contributes considerably to the diagnosis of hepatocarcinoma in patients with hepatic cirrhosis. We report the case of a cirrhotic patient whose elevated alphafetoprotein level was not associated with liver disease. CASE REPORT: Alphafetoprotein level was followed in a 64-year-old man with hepatic cirrhosis. A rise from 415 to 7690 ng/ml between June and November 1997 led to the discovery of adenocarcinoma of the cardia with liver metastasis. This extrahepatic adenocarcinoma was probably the cause of inappropriate secretion of alphafetoprotein. DISCUSSION: Primary liver tumors are obviously not the only source of elevated alphafetoprotein levels. High levels can also be observed in certain, notably digestive tract and embryonary, cancers. Gastric hepatoid adenocarcinoma is a recently described histological entity first described in 1970. Typically, there is an inappropriate secretion of alphafetoprotein due to a secondary liver tumor.

Adenocarcinoma↗

A dose-ranging study of pegylated interferon alfa-2b and ribavirin in chronic hepatitis C. The Hepatitis C Intervention Therapy Group.

The objectives of this study were to assess the safety, pharmacokinetics, and efficacy of pegylated interferon alfa-2b (PEG-Intron) plus ribavirin in patients with chronic hepatitis C. A total of 72 patients (35 men/37 women, age range 20-68 years) with clinically compensated chronic hepatitis C virus (HCV) were enrolled into this open-label, randomized, active controlled study. Patients received either PEG-Intron 0.35, 0.7, or 1.4 microg/kg subcutaneously weekly for 24 weeks alone, or in combination with ribavirin 600, 800, or 1,000 to 1,200 mg orally daily. Patients were evaluated during treatment and after a 24-week follow-up period for safety and efficacy. Detailed pharmacokinetic assessments were performed at weeks 1 and 4. PEG-Intron alone produced expected dose-related reductions in white cells, neutrophils and platelets. Addition of ribavirin reduced hemoglobin levels in a dose-related manner, did not further reduce PEG-Intron-induced decreases in neutrophil or white cell count, and increased platelet counts. Neutrophil function tests (C5a and FMLP migration, killing curves) were unaltered. Reported adverse events (flu-like symptoms, asthenia) were qualitatively similar in all dose groups. Anti-HCV activity, as measured by loss of detectable serum HCV RNA (i.e. <100 copies/mL) at the end of treatment (week 24) and after 24 weeks of follow-up (week 48) showed dose-response trends for PEG-Intron. At each PEG-Intron dose level, anti-HCV activity was higher in patients coadministered ribavirin than in patients treated with PEG-Intron monotherapy. There was no evidence of pharmacokinetic interactions with either drug. We conclude that the safety and tolerability of combined PEG-Intron/ribavirin and PEG-Intron alone were comparable. Combined PEG-Intron/ribavirin showed dose-related synergistic anti-HCV effects, which were numerically superior to those obtained with PEG-Intron monotherapy.

Adult↗

Pegylated interferon-alpha2b: pharmacokinetics, pharmacodynamics, safety, and preliminary efficacy data. Hepatitis C Intervention Therapy Group.

AIMS: The objectives of this study were to assess the safety, pharmacokinetic and pharmacodynamic profiles, and antiviral efficacy of pegylated interferon-alpha2b monotherapy in patients with chronic hepatitis C. METHODS: Fifty-eight patients (38 men, 20 women; age range, 25 to 65 years) with compensated chronic hepatitis C were enrolled in this open-label, randomized, active controlled study. Patients received 0.035 to 2.0 microg/kg pegylated interferon-alpha2b subcutaneously weekly or the active control, interferon-alpha2b 3 million IU subcutaneously three times/week, for 24 weeks. Safety and antiviral efficacy assessments were performed during treatment and in a subsequent 4-week follow-up period. Detailed pharmacokinetic assessments were performed at weeks 1 and 4. RESULTS: Pegylated interferon-alpha2b produced dose-related reductions in white blood cells, neutrophils, and platelets, and dose-related increases in oral temperature, serum neopterin, and serum 2'5'-oligoadenylate synthetase activity, which were qualitatively similar to those produced by nonpegylated interferon-alpha2b. Reported adverse events (flu-like symptoms, asthenia) were qualitatively similar in pegylated interferon-alpha2b- and nonpegylated interferon-alpha2b-treated groups. Dose-related antiviral activity, as measured by loss of detectable serum hepatitis C virus RNA (<100 copies/mL), was noted at the end of treatment and after 4 weeks of follow-up. Both pegylated and nonpegylated interferon-alpha2b were rapidly absorbed, with maximal concentrations occurring approximately 8 to 12 hours after dose administration. Pegylated interferon-alpha2b had sustained maximal serum concentrations for 48 to 72 hours after dose administration, whereas nonpegylated interferon-alpha2b concentrations declined rapidly. Volume of distribution for both compounds was similar (approximately 1 L/kg). Pegylated interferon-alpha2b elimination half-life was approximately 10-fold greater, and mean apparent clearance was one tenth that of nonpegylated interferon-alpha2b. CONCLUSIONS: Pegylated and nonpegylated interferon-alpha2b safety and pharmacodynamic profiles were comparable. Pegylated interferon-alpha2b demonstrated delayed clearance compared with nonpegylated interferon-alpha2b, consistent with once-weekly administration.

Absorption↗

[Percutaneous hepatic puncture biopsy in ambulatory care. 231 patients].

OBJECTIVES: The aim of this study was to verify that percutaneous liver biopsy does not require prolonged hospitalization over 24 hours and can be performed in a day care clinic without increased morbidity. PATIENTS AND METHODS: Two hundred thirty-one outpatients underwent percutaneous liver biopsies in a day care clinic from November 1, 1994 to June 30, 1996. There were 136 men and 95 women, mean age 39.5 years, age range 16-72 years. Liver biopsy was performed as part of the work-up for hepatitis C in 183 patients. The biopsy was a repeat procedure in 43 patients. RESULTS: The procedure was uneventful in 230 patients. Hospitalization for 24 hours was required in one patient with a biliodigestive anastomosis who developed chills and fever due to Eschericia coli bacteremia. Two procedures were unsuccessful. CONCLUSION: This series confirms that when performed in compliance with standard rules for strictly controlled indications, morbidity after percutaneous liver biopsy is not greater in an outpatient than a classical inpatient setting.

Adolescent↗

[Primary prevention of digestive hemorrhage, caused by rupture of esophageal varices, by endoscopic sclerotherapy in patients with liver cirrhosis. Multicenter randomized controlled study].

The severity of esophageal variceal bleeding in cirrhotic patients justifies prophylactic therapy. A multicenter controlled study was carried out in Languedoc in 116 cirrhotic patients with esophageal varices and no history of bleeding. Patients were randomly assigned to two groups: 60 control patients without therapy; 56 patients treated by endoscopic sclerotherapy (209 sessions). The mean follow-up was 20 +/- 11 months. Esophageal varices disappeared in 35 patients (62.5%) or became smaller in 10 other patients (18%). Varices reappeared in 9 of these 35 patients within 3 months. Minor (fever, dysphagia, stenosis) or major complications (variceal bleeding, bacterial peritonitis) were noted in 26 patients (46%). Esophageal variceal bleeding occurred in 13 of the treated patients and in 10 control patients. Actuarial curves of bleeding and survival were similar for both groups. Twenty controls and 21 treated patients died during the study. In conclusion, prophylactic sclerotherapy of esophageal varices should not be performed in cirrhotic patients, considering lack of efficacy and high rate of side effects.

Endoscopy, Gastrointestinal↗

Identification of patients with impaired hepatic drug metabolism using a limited sampling procedure for estimation of phenazone (antipyrine) pharmacokinetic parameters.

Phenazone (antipyrine) 1g was given by short intravenous infusion to 62 study participants (10 healthy drug-free volunteers and 52 patients with chronic liver disease). A Bayesian approach was developed to determine the individual pharmacokinetic parameters of phenazone. Statistical characteristics of the population pharmacokinetic parameters were first evaluated for 30 patients. When combined with 1 plasma drug concentration from members of the second group, these led to a Bayesian estimation of individual pharmacokinetic parameters for the remaining 32 individuals. Total clearance computed by Bayesian estimation was compared with maximal likelihood estimation of this parameter, the classical procedure. No statistically significant differences were found. Performance of the developed methodology was evaluated by computing bias and precision. The mean error was 0.0477 L/h. The precision of the prediction of this parameter (0.155 L/h) remained lower than the interindividual standard deviation (0.765 L/h). This procedure enables the estimation of individual pharmacokinetic parameters for phenazone. In this study, numerous laboratory tests were performed. A highly significant correlation (p < 0.001) was found between phenazone clearance and the prothrombin time, albumin, gamma-globulin, factor V, antithrombin III, fibrinogen and total bilirubin. Discriminant analysis determined that protein, alkaline phosphatase, creatininaemia and gamma-globulin had more significant discriminating power and gave better prognostic results than those seen with the Child-Pugh test.

Adult↗

Multiple-dose pharmacokinetics of pefloxacin in patients with hepatocellular deficiency.

Multiple-dose pharmacokinetics of pefloxacin were evaluated in 25 patients with hepatocellular insufficiency. The severity of liver disease was graded A, B or C according to the Child-Pugh classification. Pharmacokinetic parameters evaluated in patients on day 1 of treatment were compared with those computed in 11 healthy volunteers (the control group) after a single dose. Blood samples were taken at frequent intervals after drug administration and assayed by high performance liquid chromatography. The mean age of patients with liver impairment was slightly greater (59.5 years, range 33 to 81 years) than that of the control group (46.7 years, range 42 to 51 years). In the patients with liver disease, the mean (+/- SD) half-life of elimination, although highly variable, was significantly longer (46.3 +/- 42.5 hours) than in the control group (11.3 +/- 3.5 hours, p < 0.001). The total clearance was significantly decreased (1.76 +/- 1.31 L/h vs 6.03 +/- 2.99 L/h in the control group). In groups B and C of the Child-Pugh classification, total body clearance was about 30% of normal values. Elimination half-life increased by 200% in group B and 373% in group C compared with values in healthy volunteers. Intergroup differences (group B vs group C of the Child-Pugh classification) were not statistically significant. The minimum concentrations inhibiting 90% of Gram-negative strains (MIC90) were exceeded by plasma pefloxacin concentrations throughout treatment. For most patients, trough plasma concentrations were above 2 mg/L and peak plasma concentrations averaged 8.5 mg/L. Large inter- and intraindividual variations in the elimination half-life, total clearance and volume of distribution were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[EC-cell pancreatic endocrine carcinoma responsible for chronic diarrhea].

Ec cell or carcinoid enterochromaffinomas are very rare among the endocrine tumors, and more specifically orthocrine tumors, of the pancreas. We report one case of primary malignant carcinoid tumor of the pancreas, with no apparent metastasis, discovered during exploration for chronic diarrhea associated with hypercalcemia, disorders of carbohydrate metabolism and a serotonin secretion. The treatment consisted in a left splenopancreatectomy associated with a left adrenectomy. The clinical and biological signs immediately disappeared and, after a time lapse of almost five years, the general condition of this patient is quite satisfactory.

Acidosis↗

[Impaired fibrinolytic response to the venous occlusion test in patients with cryptogenic colitis].

The fibrinolytic response to venous occlusion was studied in 17 patients with inflammatory bowel disease: 7 with Crohn's disease, 10 with ulcerative colitis and compared with those obtained in 20 controls. Patients with inflammatory bowel disease showed decreased tissue-type plasminogen activator antigen release (t-PA Ag), no significant Von Willebrand antigen release (vWF Ag), and a residual plasminogen activator inhibitor activity (PAI activity) after venous occlusion. These modifications were more important in the evolutive colitis group compared with the remission group. Hypofibrinolysis, as defined by a defective t-PA release, and a residual PAI activity after venous occlusion might contribute to digestive and/or extra digestive thrombotic manifestations observed during the course of inflammatory bowel diseases.

Adult↗

Impaired fibrinolytic capacity in patients with inflammatory bowel disease.

The venous occlusion test was applied to 17 patients with inflammatory bowel disease (IBD; 7 cases of Crohn's disease, 10 cases of ulcerative colitis). Results were compared to those obtained in 20 healthy matched control subjects. Patients with IBD had significantly decreased t-PA Ag release (p less than 0.001) and had no significant vWF Ag release. Residual PAI activity was evidenced after venous stasis in the IBD group but not in the control group. Hypofibrinolysis was more important in patients with an evolutive IBD than in patients with IBD in remission. Impaired systemic fibrinolytic capacity might contribute to an increased risk for thromboembolic complications and to the pathogenesis of inflammatory bowel disease.

Adult↗

Small carcinomas of the pancreas with associated chronic pancreatitis: two case reports.

Two cases of pancreatitis associated with papillary atypical hyperplastic lesions and micro-invasive cancers are reported. They are interesting from an etiopathogenic and diagnostic point of view by again illustrating the problem of transmission between hyperplastic lesions and cancer, together with the difficulties encountered in asserting the certainty of diagnosis. In each observation the association of pancreatic lesions, of all stages of hyperplasia, and of cancer can be observed. This suggests that transmission occurs between those different lesions. In such cases diagnosis of benignity or malignancy is always difficult to assert. No clinical, biological, morphological or even cytological criterion allows one to make a ruling. For this reason excision is recommended by the authors whenever the etiology of pancreatitis remains obscure and especially in the presence of important dystrophic lesions.

Adenocarcinoma↗

[Does Q fever hepatitis mimic acute alcoholic hepatitis?].

The authors report the case of a chronic alcoholic woman, hospitalized for chest pain accompanied with fever. The laboratory test mimic an acute alcoholic hepatitis; the presence of a clinical and radiological pulmonary affection led to the discovery of Q fever, the diagnosis of which was confirmed by serology and the discovery of a granuloma on histological examination of the liver.

Acute Disease↗

[Lymph node-hepatosplenic hemangioma in an adult with consumption coagulopathy and fatal cardiac insufficiency].

Hemangioendothelioma is seldom seen in adults. Its severe evolution is due, not so much to the exceptional transformation into hemangiosarcoma, but mainly to haemorrhagic complications by rupture or consumption coagulopathy and to severe cardiac insuffficiency secondary to arteriovenous shunts. The case reported here concerns a 64 year-old woman presenting pain in the left hypochondrium and splenomegaly. A splenectomy was performed and the histological findings were compatible with the diagnosis of hepato-splenoganglionic hemangioendothelioma. The evolution was unfavorable. The patient died a few months later in a picture of haemorrhagic syndrome and cardiac insufficiency. Histological findings on autopsy specimens indicated a cavernous hemangioma. The treatment of these diffuse hemangiomas is a difficult one. Hepatic artery ligation has been advocated in certain desperate situations. Nevertheless, because of a collateral circulation, recurrences are frequent.

Diagnosis, Differential↗