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Jean-Pierre Bronowicki

Publications and source records attributed to Jean-Pierre Bronowicki.

31 records · Page 2Linked to original sources
PubMed2004

A phase II dose-escalating trial of clevudine in patients with chronic hepatitis B.

Current therapies available for the treatment of chronic hepatitis B are limited in their ability to result in a cure. Clevudine is a new pyrimidine analog with potent anti-hepatitis B virus (HBV) activity in vitro. A multicenter dose-escalation study evaluated clevudine at 10, 50, 100, and 200 mg once daily for 28 days. Eligible patients had HBV DNA levels of 3 x 10(6) copies/mL or more, had not undergone nucleoside treatment, and were without human immunodeficiency or hepatitis C virus coinfection. Thirty-two patients were enrolled (5, 10, 10, and 7 patients in the 10-, 50-, 100-, and 200-mg dose groups, respectively), 81% were male, 81% Asian, and 88% were hepatitis Be antigen (HBeAg) positive at baseline. Median pretreatment serum HBV DNA levels ranged from 7.3 to 8.8 log(10) copies/mL. After 28 days, the median HBV DNA log(10) change from baseline was -2.5, -2.7, -3.0, and -2.6 log(10). Six months after dosing, median changes from baseline were -1.2, -1.4, -2.7 and -1.7 log(10) in the 10-, 50-, 100-, and 200-mg cohorts, respectively. Six of 27 patients lost HBeAg, and 3 of 27 patients seroconverted to HBe antibody. Clevudine was well tolerated, with no dose-limiting toxicities. A transient increase in alanine aminotransferase of up to 7.8 times the upper limit of normal (increase ranged from 20 to 186 IU/L) was observed in six patients in the 100-mg cohort, without signs of liver failure. These increases were associated with improved viral suppression. The pharmacokinetic profile of clevudine was proportional to the dose. In conclusion, these results demonstrate the tolerability and potent activity of clevudine in HBV-infected patients and support further clinical study.

Adult↗
PubMed2003

Vitamin B12 is a strong determinant of low methionine synthase activity and DNA hypomethylation in gastrectomized rats.

BACKGROUND/AIMS: The respective influence of folate and vitamin B12 deficiency on MTR activity and transcription, and on DNA methylation is not clearly established. The aim of this study was to assess the respective influence of folate and vitamin B12 deficiency on MTR transcription and activity, and on DNA methylation. METHODS: Sixty-one rats were administered normal diet or diet deficient in choline, methionine, folic acid and vitamin B12. Forty-seven of them underwent total gastrectomy or ileal resection. RESULTS: Low vitamin B12 was observed only in gastrectomized rats. Low folate was observed in rats under deficient diet. Total MTR activity (holo- + apoenzyme) was lowered only with vitamin B12 level <200 pmol/l (p=0.0002), while the ratios of total vs. holo-MTR activity and of transcripts MTR vs. GAPDH (RT-PCR) were unchanged. Vitamin B12 was the single determinant of low MTR (lower quartile, odds ratio=15.75, p=0.0017). Low MTR and low vitamin B12 were the two determinants of DNA hypomethylation (lower quartile) (odds ratio=17.07, p=0.0006, and odds ratio=7.31, p=0.006, respectively). CONCLUSION: Vitamin B12 affects MTR expression by a non-transcriptional mechanism different from a protective effect on MTR proteolysis. It is also a strong determinant of DNA hypomethylation.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed2003

Rate of natural disease progression in patients with chronic hepatitis C.

BACKGROUND/AIMS: The interval at which liver biopsy should be repeated in untreated patients with chronic hepatitis C is not defined. We examined fibrosis change by METAVIR scoring in these patients in whom two or more liver biopsies were available. METHODS: One hundred and eighty patients with histologically proven chronic hepatitis C were studied. Mean delay between biopsies was 3.67+/-2.69 years and 3.08+/-1.43 in the 16 patients having three biopsies. Univariate and multivariate analyses were performed to determine factors associated with liver fibrosis progression. RESULTS: Median rate of fibrosis progression per year was 0.04 (0.00-0.55) to first biopsy, 0.00 (-0.84-1.02) between first and second biopsy (NS), and 0.17 (0.00-1.50) between second and third biopsy (P<0.05). In multivariate analysis, only age at first biopsy >40 years (OR=5) (2-12) and alcohol consumption of 1-50 g per day (OR=4) (2-12) and more than 50 g per day (OR=8) (3-23) were associated with severe fibrosis. The number of patients who increased in fibrosis stage was significantly higher after 4 years (P<0.02). CONCLUSIONS: An interval of at least 4-5 years is needed between liver biopsies to measure change in patients with mild liver disease.

Adult↗
PubMed2003

Primary lymphoma of the liver: clinical-pathological features and relationship with HCV infection in French patients.

Primary lymphoma of the liver (PLL) is rare. In some cases, the hepatic lymphoma has been diagnosed in patients who were infected by the hepatitis C virus (HCV). It has been suggested that HCV plays a role in the pathogenesis of lymphoma. The aim of our multicentric retrospective study was to assess the characteristics of PLL and to determine the prevalence of HCV infection in PLL. Thirty-one immunocompetent patients (anti-human immunodeficiency virus, anti-human T-cell leukemia/lymphoma virus negative, no history of allograft) with PLL fulfilled the entire selection criteria. The liver biopsy specimens were reassessed by the same pathologist. The non-Hodgkin's lymphomas were classified according to the World Health Organization classification. Blood samples were tested in 28 patients for antibodies to HCV, and HCV RNA was detected by reverse transcription polymerase chain reaction. In the majority of cases, the clinical, biologic, and radiologic data were nonspecific. Twenty-seven of 31 patients presented a B-cell lymphoma corresponding to the centroblastic morphologic variant of a diffuse, large B-cell lymphoma (22 cases), a Burkitt's lymphoma (1 case), an extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type (3 cases), and unclassified, small B-cell lymphoma (1 case). The 4 other cases were T-cell lymphomas. The prevalence of HCV infection was 21% (6 of 28 cases). All of these patients were positive for HCV RNA by polymerase chain reaction in blood. Most of the HCV-infected patients presented a high-grade, B-cell type lymphoma. In conclusion, our study confirms the rarity of PLL and demonstrates an increased prevalence of HCV infection.

Adult↗
PubMed2003

Effects of vitamin B12 and folate deficiencies on DNA methylation and carcinogenesis in rat liver.

Deficiencies of the major dietary sources of methyl groups, methionine and choline, lead to the formation of liver cancer in rodents. The most widely investigated hypothesis has been that dietary methyl insufficiency results in abnormal DNA methylation. Vitamin B12 and folate also play important roles in DNA methylation since these two coenzymes are required for the synthesis of methionine and S-adenosyl methionine, the common methyl donor required for the maintenance of methylation patterns in DNA. The aim of this study was to review the effects of methyl-deficient diets on DNA methylation and liver carcinogenesis in rats, and to evaluate the role of vitamin B12 status in defining carcinogenicity of a methyl-deficient diet. Several studies have shown that a methyl-deficient diet influences global DNA methylation. Evidence from in vivo studies has not clearly established a link between vitamin B12 and DNA methylation. We reported that vitamin B12 and low methionine synthase activity were the two determinants of DNA hypomethylation. Choline- or choline/methionine-deficient diets have been shown to cause hepatocellular carcinoma in 20-50% of animals after 12-24 months. In contrast, the effect of vitamin B12 withdrawal, in addition to choline, methionine and folate, induced hepatocellular carcinoma in less than 5% of rats.

Animals↗
PubMed2002

Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection.

BACKGROUND: Some epidemiologic studies suggest a link between hepatitis C virus (HCV) infection and some B-cell non-Hodgkin's lymphomas. We undertook this study after a patient with splenic lymphoma with villous lymphocytes had a hematologic response after antiviral treatment of HCV infection. METHODS: Nine patients who had splenic lymphoma with villous lymphocytes and HCV infection were treated with interferon alfa-2b (3 million IU three times per week) alone or in combination with ribavirin (1000 to 1200 mg per day). The outcomes were compared with those of six similarly treated patients with splenic lymphoma with villous lymphocytes who tested negative for HCV infection. RESULTS: Of the nine patients with HCV infection who received interferon alfa, seven had a complete remission after the loss of detectable HCV RNA. The other two patients had a partial and a complete remission after the addition of ribavirin and the loss of detectable HCV RNA. One patient had a relapse when the HCV RNA load again became detectable in blood. In contrast, none of the six HCV-negative patients had a response to interferon therapy. CONCLUSIONS: In patients with splenic lymphoma with villous lymphocytes who are infected with HCV, treatment with interferon can lead to regression of the lymphoma.

Adult↗
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↗
PubMedDate not supplied

Contribution of computed tomography with oral media contrast to the diagnosis of esophago-pericardial fistula.

The esophago-pericardial fistula is a very rare and usually fatal complication of esophageal cancers. We report a case of a 56-year-old man who presented with chest pain 1 month after concurrent radiochemotherapy for squamous cell esophageal carcinoma. Thoracic computed tomography (CT) with oral iodinated media contrast revealed esophago-pericardial fistula visualizing the fistulous tract. We conclude that CT with oral contrast media may be the first imaging technique of choice to confirm the diagnosis of esophago-pleural fistula.

Administration, Oral↗