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Alexandre Pariente

Publications and source records attributed to Alexandre Pariente.

At least 19 recordsLinked to original sources
PubMed2006

Genetic polymorphisms of MMP1, MMP3 and MMP7 gene promoter and risk of colorectal adenoma.

BACKGROUND: Matrix metalloproteinases (MMP) have been shown to play a role in colorectal cancer (CRC). More recently, MMP1, MMP3 and MMP7 functional gene promoter polymorphisms have been found to be associated with CRC occurrence and prognosis. To document the role of MMP polymorphisms in the early step of colorectal carcinogenesis, we investigated their association with colorectal adenoma risk in a case-control study comprising 295 patients with large adenomas (LA), 302 patients with small adenomas (SA) and 568 polyp-free (PF) controls. METHODS: Patients were genotyped using automated fragment analysis for MMP1 -1607 ins/del G and MMP3 -1612 ins/delA (MMP3.1) polymorphisms and allelic discrimination assay for MMP3 -709 A/G (MMP3.2) and MMP7 -181 A/G polymorphisms. Association between MMP genotypes and colorectal adenomas was first tested for each polymorphism separately and then for combined genotypes using the combination test. Adjustment on relevant variables and estimation of odds ratios were performed using unconditional logistic regression. RESULTS: No association was observed between the polymorphisms and LA when compared to PF or SA. When comparing SA to PF controls, analysis revealed a significant association between MMP3 -1612 ins/delA polymorphism and SA with an increased risk associated with the 6A/6A genotype (OR = 1.67, 95% CI: 1.20-2.34). Using the combination test, the best association was found for MMP3.1-MMP1 (p = 0.001) with an OR of 1.88 (95% CI: 1.08-3.28) for the combined genotype 2G/2G-6A/6A estimated by logistic regression. CONCLUSION: These data show a relation between MMP1 -1607 ins/del G and MMP3 -1612 ins/delA combined polymorphisms and risk of SA, suggesting their potential role in the early steps of colorectal carcinogenesis.

Adenomatous Polyps↗
PubMed2006

High dose daily interferon-alpha induction and secondary adjunction of ribavirin in treatment-naive patients with chronic hepatitis C. A multicentric, randomised, controlled trial.

OBJECTIVES: To evaluate in naive patients with chronic hepatitis C 1- the efficacy and safety of one month interferon alpha (IFN-alpha) induction regimen; 2- the potential virological benefit of a secondary adjunction of ribavirin among HCV RNA negative patients after 20 weeks of IFN therapy, with or without an initial 4-week IFN induction. MATERIAL AND METHODS: 151 naive HCV-RNA positive patients presenting with biopsy- proven chronic hepatitis C and elevated ALT were randomised in a 2: 1 ratio in two arms: IFN-alpha 3 MU thrice a week (tiw) for 24 weeks (non-induced patients); IFN-alpha 6 MU daily for two weeks, then 3 MU daily for two weeks then 3 MU tiw for 20 weeks (induced patients). At week 24, HCV-RNA negative patients were randomised to receive in addition or not ribavirin 1-1.2 g daily for 24 additional weeks. Induction efficacy was assessed on the early viral response (EVR) defined as undetectable HCV RNA at week 4 then week 20. Ribavirin efficacy was assessed on the proportion of maintained complete response until the end of follow-up, 24 weeks after discontinuation of treatment. Data were analysed on an intent-to-treat basis. RESULTS: Efficacy of IFN-alpha induction: 104 patients were randomised to the non-induction group, 47 to the induction group. Gender, age, genotype distribution and HCV viral load at baseline did not differ significantly between the two groups. There was one treatment discontinuation because of adverse events in induced patients versus four in non-induced patients (P > 0.05). The 4 week EVR was significantly greater in induced patients in patients with HCV genotype 1, 4 or 5 (47% vs 12%, P=0.0002) only. There was no impact of induction in patients with HCV genotype 2 or 3. Efficacy of ribavirin: at week 24, 28 and 26 HCV-RNA negative patients were randomised to addition of ribavirin or not, respectively. Patients randomised to secondary additive ribavirin were more often HCV-RNA negative at the end of follow-up than patients treated with IFN-alpha alone: 18/28 (64%) vs 10/26 (39%); P=0.06. Among patients randomised to bitherapy, the relapse rate was significantly lower in patients with genotype 2 or 3 (0/12 vs 6/13, P=0.01) and not in those with genotype 1, 4 or 5 (5/11 vs 3/6, P=0.99). CONCLUSION: A 4 week IFN-alpha induction significantly increases the EVR rate in patients with HCV genotype 1, 4 or 5. Late secondary adjunction of ribavirin to IFN-alpha for 6 months in HCV-RNA negative patients after 6 months of IFN-alpha significantly decreases the relapse rate in patients with HCV genotype 2 or 3, but not in patients with genotypes 1, 4 or 5.

Adult↗
PubMed2006

Severe sinusoidal lesions: a serious and overlooked complication of oxaliplatin-containing chemotherapy?

The main toxicity of Oxaliplatin, a major drug in the treatment of metastatic colorectal carcinoma, is neurologic. Severe sinusoidal lesions of the liver have been recently described in patients receiving pre-operative (neoadjuvant) oxaliplatin-containing chemotherapy, but their clinical relevance is unknown. Four patients with metastatic colon cancer receiving oxaliplatin, 5 fluorouracil and elvorin, developped a progressive increase in gammaglutamyl transpeptidase and alkaline phosphatase, contrasting with tumour regression established by CT-scan and decrease in serum carcinoembryonic antigen concentrations. Histological examination of liver biopsies showed sinusoidal dilatation in all cases, with perisinusoidal fibrosis and centrilobular vein lesions in 3, peliosis in 1 (in a patient receiving oxaliplatine by intraarterial hepatic route), and nodular regenerative hyperplasia in 1. The patient with peliosis developped ascites, and died from hepatic failure, despite withdrawal of the drug. The patient with nodular regenerative hyperplasia developped jaundice, ascites and severe infection following a right hepatectomy. In the three surviving patients, liver function tests improved after the withdrawal of oxaliplatin, and, in one, deteriorated again after reintroduction of the drug. The prevalence of liver sinusoid lesions induced by oxaliplatin-containing chemotherapeutic regimens is probably underestimated. Careful monitoring of gamma-glutamyl transpeptidase and alkaline phosphatase is mandatory in treated patients, especially in those receiving adjuvant therapy, in whom significant sequelae could occur despite initially asymptomatic lesions.

Adenocarcinoma↗
PubMed2006

Imatinib mesylate-induced acute hepatitis in a patient treated for gastrointestinal stromal tumour.

We report the first case of hepatocellular injury occurring in a patient treated for metastatic gastrointestinal stromal tumour (GIST) with imatinib mesylate, with two positive rechallenges including one with 2.5% of the current therapeutic dosage. The patient could be treated later with sunitinib without liver toxicity. Grade 3-4 liver toxicity could occur in one out of 40 treated patients with imatinib for GIST, and fatalities have been reported. Regular monitoring of liver function tests is essential in patients treated with imatinib.

Aged↗
PubMed2005

Randomized controlled trial of tamoxifen in advanced hepatocellular carcinoma.

PURPOSE: Randomized studies on tamoxifen treatment of hepatocellular carcinoma (HCC) produced conflicting results. The aim of this study was to assess the efficacy of tamoxifen administration in improving overall survival of patients with advanced HCC. PATIENTS AND METHODS: A total of 420 patients with HCC who were not suitable for surgery or local treatment were randomly assigned between April 1995 and May 2000: 210 in the control group and 210 in the tamoxifen group (20 mg/d orally). Patients with WHO performance status greater than 2, belonging to Child-Pugh class C, or with serum creatinine greater than 130 mumol/L were not eligible. RESULTS: Tolerance was good and the main reported adverse effects were thrombophlebitis (three patients), nausea (two patients), and hot flushes (three patients). Outcome did not differ between the two treatment arms: estimated median survival was 4.8 and 4.0 months in the tamoxifen and in the control groups, respectively (P = .25). Univariate analysis showed significant association of survival with age, Okuda stage, WHO performance status, Child-Pugh class, intrahepatic tumor stage, alpha-fetoprotein serum concentration, and presence of extrahepatic spread, portal vein thrombosis, hepatomegaly, or hepatalgia. In a Cox proportional hazards model we found a significant beneficial effect of tamoxifen on survival in patients belonging to Okuda I or II stages. CONCLUSION: In this large study, tamoxifen did not improve the survival of patients with advanced HCC, but there is a suggestion that patients without major hepatic insufficiency seem to have some survival benefit. New trials involving this specific population are warranted.

Aged↗
PubMed2005

Diagnostic criteria in predicting a biliary origin of acute pancreatitis in the era of endoscopic ultrasound: multicentre prospective evaluation of 213 patients.

BACKGROUND: No study on bioclinical criteria predicting a biliary origin for acute pancreatitis has included endosonography as a reference examination. Re-examination of bioclinical parameters deserves consideration in the era where other causes are known (e.g. hereditary, autoimmune). AIM AND METHODS: To determine the performance of bioclinical markers in predicting a biliary origin of acute pancreatitis where the diagnosis of biliary lithiasis was established or ruled out using endosonography. Only patients with a first acute episode of pancreatitis were included. RESULTS: 213 patients (male: 55%; median age: 56 years) were prospectively included in 14 centres. Causes of acute pancreatitis were: biliary (62%), alcoholic (25%), other (13%). Delay between symptom-onset and admission was <48 h in 80%. Endosonography was the sole method establishing the diagnosis of biliary pancreatitis in 15% of patients. At univariate analysis, age, female sex, declared alcohol consumption, elevated aspartate and alanine transaminases on admission, gammaglutamyl transferase, alkaline phosphatase, total bilirubin, lipase, mean corpuscular volume were predictive of a biliary origin. Only age (p < 0.0001), sex (p < 0.0008) and alanine transaminase (p < 0.0004) remained significant at multivariate analysis. At age 50, the respective sensitivity and specificity were 73 and 65%. With an elevated alanine transaminase at 2 times the upper limit of normal range, the respective sensitivity and specificity were 74 and 84%. The probability of a biliary origin of acute pancreatitis could be estimated by the following formula: = 1/1 + exp(4.6967 - 0.0656 x age + 1.1208 x sex - 0.6909 x alanine transaminase). CONCLUSION: When endosonography is performed to confirm or exclude a biliary origin of acute pancreatitis, age, sex and alanine transaminase at admission are the only factors predictive of a biliary cause.

Acute Disease↗
PubMed2005

[How to measure liver fibrosis in viral hepatitis?].

During viral hepatitis, the evaluation of the fibrosis has, above-all, a prognostic value. The complications of the illness only appear after the onset of cirrhosis in the great majority of cases. Liver biopsy remains the gold standard but has intrinsic limits linked to its size and the heterogeneity of the lesions in the liver, and is extrinsically linked to inter-observer variability (quite insignificant for fibrosis when using the METAVIR classification). The biopsy causes very little morbidity and insignificant mortality, however it does necessitate hospitalisation. Among the isolated hepatic blood markers, the prothrombin level and the hyaluronic acid have good specificity but insufficient sensitivity for the diagnosis of severe fibrosis. Among the tests combining several markers, the FibroTest is the best studied and the best performing, at least in the case of hepatitis C. It must be interpreted with caution due to the possible variations of its different constituents not linked to hepatic fibrosis. Ultrasound has a good specificity but its sensitivity is insufficient for the diagnosis of cirrhosis. Elastography, a non-invasive percutaneous technique, is promising. The FibroTest must be used as first-line, notably in hepatitis C, however is not currently covered by the National Health Insurance (assurance-maladie). Apart from in therapeutic trials, the liver biopsy should only be proposed in the case of uncertainty about the degree of fibrosis and, above-all, the existence of cirrhosis, and only then when there are practical implications.

Biomarkers↗
PubMed2005

[When should a stool culture be done in adults with nosocomial diarrhea?].

OBJECTIVE: To assess the diagnostic efficacy, cost and possible corrective measure of the indications for routine stool cultures in nosocomial diarrhoea in adults. METHODS: A retrospective study over a 10-month period of 660 standard stool cultures, 256 of which were conducted after the 3rd day of hospitalisation, conducted in 528 patients at the hospital centre in Pau. RESULTS: The positivity rate of the stool cultures was of 26/336 patients (7.7%), and of 37/404 examinations (9%) within the first three days of hospitalisation, versus 2/192 patients (1%) and 3/256 examinations (1%) after the 3rd day of hospitalisation (p<0.05). In 83 patients a stool culture was repeated, and was only positive in one patient with an initially negative culture. If a stool culture had not been performed after the 3rd day, 2 infections would not have been diagnosed (1 salmonella and 1 K. oxytoca) and 256 stool cultures could have been economised (estimated cost: 6,144 euro). Moreover, by eliminating repeated stool cultures, 3 infections would not have been diagnosed (2 salmonella, and 1 K. oxytoca) and 321 stool cultures would have been avoided (estimated cost: 7,704 euro). If the stool cultures had been conducted after the 3rd day of hospitalisation only in those aged over 64 with comorbidity, immunosuppression or within the context of an epidemic, no false negative would have been observed and 149 stool cultures would have been economised (estimated cost: 3,576 euro). The positivity rate of the search for C. difficile, only conducted on explicit request from the practitioners, was of 5/23 (22%) and 4/28 (14%) before and after the 3rd day of hospitalisation (non-significant difference). CONCLUSION: Restriction of standard stool cultures after the 3rd day of hospitalisation to patients aged over 64 with comorbidity, to the immunodepressed, and within an epidemic context would economise around 4,300 euro per month in a medium-sized general hospital. No systematic restriction should be applied to the search for C. difficile.

Adult↗
PubMed2005

The underestimated role of opiates in patients with suspected sphincter of Oddi dysfunction after cholecystectomy.

AIMS: Pain recurrence after cholecystectomy is often attributed to sphincter of Oddi dysfunction, whose diagnostic criteria and treatments remain uncertain. We performed a retrospective study to assess the possible precipitating role of opiate ingestion in this setting. METHODS: The retrospective study of the files of 147 consecutive patients investigated for post-cholecystectomy syndrome by endoscopic ultrasonography and/or endoscopic retrograde cholangiography yielded 37 cases of suspected biliary-type sphincter of Oddi dysfunction. RESULTS: Thirteen patients (30%) with suspected sphincter of Oddi dysfunction had taken opiate-containing drugs 15 minutes to two hours (median 1 hr) before the onset of pain ("Opiate group"). When compared with the 23 patients having not taken opiates ("Non Opiate Group"), they were significantly younger (47 vs. 60 yrs), had a narrower common bile duct (5.0 vs. 7.7 mm), but had similar biochemical abnormalities and belonged to the same Milwaukee's classes, mainly class II. None of the patients in the "Opiate group" were submitted to retrograde cholangiography or endoscopic sphincterotomy vs. 52% and 39%, respectively of the patients of the "Non-Opiate Group". After a mean follow-up of 3.5 years, there were three recurrences of biliary-type pain (1 choledochal stone, and 2 suspected sphincter of Oddi dysfunction) in the "Opiate Group", and 2 (1 choledochal stone, 1 after codeine intake) in the "Non-Opiate Group". CONCLUSIONS: Opiate intake is a frequent cause of suspicion of sphincter of Oddi dysfunction after cholecystectomy, especially in young patients with a narrow common bile duct. A careful history taking is essential to avoid unnecessary and potentially harmful procedures.

Age Distribution↗
PubMed2003

CATSPER2, a human autosomal nonsyndromic male infertility gene.

In the course of positional cloning of the Congenital Dyserythropoietic Anemia type I (CDAI) [MIM 224120] gene on 15q15.1-15.3, we examined a family of French origin, in which the propositus suffered from asthenoteratozoospermia and nonsyndromic deafness in addition to CDAI. Two of his brothers had a similar phenotype. All three siblings were homozygous carriers of the CDA1 mutation as well as of a distally located approximately 70 kb deletion of the proximal copy of a 106 kb tandem repeat on chromosome 15q15. These repeats encode four genes whose distal copies may be considered pseudogenes. Lack of functional stereocilin and CATSPER2 (a voltage-gate cation channel expressed specifically in spermatozoa) may explain the observed deafness and male infertility phenotypes. To the best of our knowledge, the involvement of CATSPER2 in asthenoteratozoospermia is the first description of a human autosomal gene defect associated with nonsyndromic male infertility.

Anemia, Dyserythropoietic, Congenital↗
PubMed2003

[Treatment of chronic hepatitis C with interferon alpha and ribavirin. Results in "real life"].

OBJECTIVES: The applicability of the results of controlled, randomised, therapeutic trials in the general population is not well known. The aim of this prospective study was to assess the results of the treatment of chronic hepatitis C with interferon alpha and ribavirin in "real life." METHODS: In an independent observatory, clinicians from 31 hepatogastroenterology units in French general hospitals registered patients treated with interferon alpha and ribavirin outside clinical trials. Results were compared with those of the best arm (twelve months of bitherapy) of the European-Canadian trial published in 1998 by Poynard et al. RESULTS: 262 naïve patients were included. Patients were significantly older, had more severe liver fibrosis, with cirrhosis in 17 percent, but were comparable for sex, contamination mode and viral genotype with those of the Poynard et al. trial. Sustained virological response rate (37%, IC 95%: 31-43%) was not significantly lower (difference 6%, IC 95%: - 18% to + 6%) than in the Poynard et al. trial. Results for response factors were similar. Comorbid conditions which would have prevented our inclusion of patients in the Poynard et al. trial were present in 46% and had an independent negative effect on sustained virological response rate. Side-effects were similar. CONCLUSIONS: The efficacy of the combination of interferon alpha and ribavirin remains good in real life, but depends on the characteristics of the treated population. The results of trials should be presented more cautiously to general population.

Antiviral Agents↗
PubMed2002

Congenital dyserythropoietic anemia type I is caused by mutations in codanin-1.

Congenital dyserythropoietic anemias (CDAs) constitute a rare group of inherited red-blood-cell disorders associated with dysplastic changes in late erythroid precursors. CDA type I (CDAI [MIM 224120], gene symbol CDAN1) is characterized by erythroid pathological features such as internuclear chromatin bridges, spongy heterochromatin, and invagination of the nuclear membrane, carrying cytoplasmic organelles into the nucleus. A cluster of 45 highly inbred Israeli Bedouin with CDAI enabled the mapping of the CDAN1 disease gene to a 2-Mb interval, now refined to 1.2 Mb, containing 15 candidate genes on human chromosome 15q15 (Tamary et al. 1998). After the characterization and exclusion of 13 of these genes, we identified the CDAN1 gene through 12 different mutations in 9 families with CDAI. This 28-exon gene, which is transcribed ubiquitously into 4738 nt mRNA, was reconstructed on the basis of gene prediction and homology searches. It encodes codanin-1, a putative o-glycosylated protein of 1,226 amino acids, with no obvious transmembrane domains. Codanin-1 has a 150-residue amino-terminal domain with sequence similarity to collagens and two shorter segments that show weak similarities to the microtubule-associated proteins, MAP1B (neuraxin) and synapsin. These findings, and the cellular phenotype, suggest that codanin-1 may be involved in nuclear envelope integrity, conceivably related to microtubule attachments. The specific mechanisms by which codanin-1 underlies normal erythropoiesis remain to be elucidated.

Amino Acid Sequence↗
PubMed2002

Terlipressin in patients with cirrhosis and type 1 hepatorenal syndrome: a retrospective multicenter study.

BACKGROUND & AIMS: Type 1 hepatorenal syndrome (HRS) is a severe complication of cirrhosis associated with a short median survival time (<2 weeks). Although the administration of terlipressin improves renal function, its effect on survival is unknown. This study investigated predictive factors of survival in patients with type 1 HRS treated with terlipressin. METHODS: Ninety-nine patients with type 1 HRS treated with terlipressin in 24 centers were retrospectively studied. Terlipressin-induced improved renal function was defined as a decrease in serum creatinine value to <130 micromol/L or a decrease of at least 20% at the end of treatment. RESULTS: At inclusion, the Child-Pugh score was 11.8 +/- 1.6 (mean +/- SD). Terlipressin (3.2 +/- 1.3 mg/day) was administered for 11 +/- 12 days. Renal function improved in 58% of patients (serum creatinine decreased by 46% +/- 17% from 272 +/- 114 micromol/L). Median survival time was 21 days. Survival rate was 40% at 1 month. Multivariate analysis showed that improved renal function and Child-Pugh score < or =11 at inclusion were independent predictive factors of survival (P < 0.0001 and 0.02, respectively). Thirteen patients underwent liver transplantation (92 +/- 95 days after HRS onset), 10 of whom had received terlipressin and had had improved renal function. CONCLUSIONS: This retrospective uncontrolled study shows that in patients with type 1 HRS, terlipressin-induced improved renal function is associated with an increase in survival. Thus, a randomized trial investigating the effect of terlipressin on survival in patients with type 1 HRS should be performed.

Aged↗
PubMed2002

[Acute hepatitis C: a retrospective study of 62 cases].

OBJECTIVES: Retrospective study of acute hepatitis C cases observed in general hospitals. METHODS: Questionnaire sent by mail to members of the Association Nationale des Gastroentérologues des Hôpitaux Généraux (ANGH) in December, 1997. Data were updated in September, 2001. RESULTS: Sixty-two cases were reported in 40 centers. Patients were predominantly female (58%), the median age was 33 years-old. Symptoms revealed the disease in 65% of cases (jaundice in 53%) and screening in 30%. The main suspected routes of infection were intravenous drug use (32%), nosocomial exposure (29%) and professional accidents (11%). Sustained viral clearance occurred in 12 out of the 28 patients who were followed without treatment for 6 months, in 14 of 30 treated early, and 4 out of 7 treated secondarily with interferon alpha alone. No prognostic factor was identified, except for a low total dose of interferon in treated patients. CONCLUSIONS: Acute hepatitis C is a rare disease, occurring in younger and more often in female patients than chronic hepatitis C. Spontaneous cure is not infrequent, and could justify a period of simple follow-up before starting treatment. A national observatory would help for epidemiologic surveillance and therapeutic studies.

Acute Disease↗