PubMed Health⌕ Search

Biomedical subjects

N Boyer

Publications and source records attributed to N Boyer.

At least 37 records · Page 2Linked to original sources
PubMed2000

A new step toward standardization of serum hepatitis C virus-RNA quantification in patients with chronic hepatitis C.

The need to improve efficacy of antiviral therapy for chronic hepatitis C has prompted the development of quantitative assays, which allows the assessment of viral load before therapy. The aim of our study was to evaluate the clinical relevance of 3 serum HCV-RNA quantitative assays in 87 patients with chronic hepatitis C, the noncommercially available SuperQuant assay (National Genetic Institute), recently used in large international controlled trials, the most early and widely used Quantiplex HCV RNA v2.0 assay (branched DNA [bDNA] v2.0; Bayer Diagnostics, Puteaux, France), and the new generation Cobas Amplicor HCV Monitor assay (COBAS v2.0; Roche Diagnostics Systems, Meylan, France), which is a semiautomated reverse transcription-polymerase chain reaction (RT-PCR) assay. The level and range of quantification were similar between all assays and a strong correlation was observed over all HCV genotypes among the assays. Recent publications have suggested that the baseline cut-off level of 2 x 10(6) copies/mL, as determined by the SuperQuant assay, is able to discriminate between patients with low viral load from those with high viral load and can be used to predict responses to therapy. Because all 3 assays use different testing technologies we examined how many of our patients fell above this defined cut-off level when tested by the other assays; of 22 patients measured below 2 x 10(6) copies/mL with the SuperQuant assay, 17 of 22 and 19 of 22 patients were eligible with the bDNA v2. 0 and the COBAS v2.0 assays, respectively (P >.05). Our results indicate that the 2 commercial assays can be used to determine treatment schedules in patients with chronic hepatitis C, providing a flexibility in multicenter controlled trials by offering better accessibility of test results.

Enzyme-Linked Immunosorbent Assay↗
PubMed2000

Decrease in serum ALT and increase in serum HCV RNA during pregnancy in women with chronic hepatitis C.

BACKGROUND/AIMS: The natural history of chronic hepatitis C infection during pregnancy has not been clearly established, and thus our aim was to assess serum alanine aminotransferase levels and serum HCV RNA levels during pregnancy. METHODS: Twenty-six pregnant women with chronic hepatitis C were studied. Serum alanine aminotransferase was assessed within the 3 months before, monthly during and within the 3 months after pregnancy. In 12 women, serum HCV RNA levels were quantified by the branched DNA assay. Twenty-six age-matched non-pregnant women with chronic hepatitis C were followed up for 1 year, and used as a comparison group. RESULTS: During pregnancy, serum alanine aminotransferase levels decreased in the second and third trimesters. The third trimester levels were significantly lower than serum alanine aminotransferase levels before pregnancy (p=0.0001). Seventy-seven percent of the pregnant women with increased pre-pregnancy levels had normalization of serum alanine aminotransferase levels. In the second or third trimesters, serum HCV RNA levels increased. The third trimester serum HCV RNA levels were significantly higher than levels before pregnancy (p=0.01). No significant change in serum alanine aminotransferase or HCV RNA levels was observed in the control group. CONCLUSION: In pregnant women with chronic hepatitis C, serum alanine aminotransferase levels decrease, and serum HCV RNA levels increase during the second and third trimesters.

Adult↗
PubMed2000

Pathogenesis, diagnosis and management of hepatitis C.

The hepatitis C virus (HCV) is the leading cause of chronic liver disease worldwide. It is estimated that about 170 million people are chronically infected with HCV. Chronic hepatitis C is a major cause of cirrhosis and hepatocellular carcinoma and HCV-related end-stage liver disease is, in many countries, the first cause of liver transplantation. HCV infection is characterized by its propensity to chronicity. Because of its high genetic variability, HCV has the capability to escape the immune response of the host. HCV is not directly cytopathic and liver lesions are mainly related to immune-mediated mechanisms, which are characterized by a predominant type 1 helper cell response. Co-factors influencing the outcome of the disease including age, gender and alcohol consumption are poorly understood and other factors such as immunologic and genetic factors may play an important role. Recent studies have shown that the combination therapy with alpha interferon and ribavirin induces a sustained virological response in about 40% of patients with chronic hepatitis C. The sustained response rates are mainly dependent on the viral genotype (roughly 60% in genotype non-1 and 30% in genotype 1). Reliable diagnostic tools are now available and useful for detecting HCV infection, to quantify viral load and to determine the viral type. The assessment of the viral quasispecies and the characterization of viral sequences might be clinically relevant but standardized and simple techniques are needed. The lack of animal models and of in vitro culture systems hampers the understanding of the pathogenesis of chronic hepatitis C and the development of new antivirals. New therapeutic schedules with higher and/or daily doses of alpha interferon do not seem to improve the efficacy greatly. The conjugation with polyethylene glycol (PEG) improved the pharmacodynamics and the efficacy of alpha interferon. Emerging new therapies include inhibitors of viral enzymes (protease, helicase and polymerase), cytokines (IL-12 and IL-10), antisense oligonucleotides and ribozymes. The first candidate compounds should be available in the next few years. The development of an effective vaccine remains the most difficult and pressing challenge. Because of the high protein variability of HCV, protective vaccines could be extremely difficult to produce and therapeutic vaccines seem more realistic. Considerable progress has been made in the field of HCV since its discovery 10 years ago but a major effort needs to be made in the next decade to control HCV-related liver disease.

Antiviral Agents↗
PubMed2000

A pilot study of recombinant interferon beta-1a for the treatment of chronic hepatitis C.

AIMS: Interferon alpha monotherapy induces a sustained response in less than 20% of patients treated for chronic hepatitis C. Interferon beta represents a potential therapeutic alternative for the treatment of chronic hepatitis C. The aim of this pilot study was to evaluate the efficacy and tolerance of recombinant interferon beta-la administered subcutaneously. METHODS: Twenty-one drug-naive patients with chronic hepatitis C were treated with recombinant interferon beta-la administered, subcutaneously, for 24 weeks using two different regimens: 9 MU, three times per week (n=11) and 12 MU, three times per week (n=10). RESULTS: At the end of the treatment period, nine (43%) patients had a biochemical and virological response (i.e. normal ALT and absence of hepatitis C virus RNA by PCR). Four of these patients were in the 9 MU group and five in the 12 MU group. A biochemical and virological sustained response occurred in four (19%) patients, all in the 9 MU dose group. The 4 patients with a sustained response maintained their response during a follow-up period of 33 to 58 months. Side effects were mild and 19 (90%) patients completed the treatment period. CONCLUSIONS: The results of this pilot study indicate that interferon beta-la administered subcutaneously is an effective therapy for some patients with chronic hepatitis C, and suggest that interferon beta-1a deserves further evaluations in larger trials especially in combination with ribavirin.

Adult↗
PubMed1999

Predictors of sustained response to alpha interferon therapy in chronic hepatitis C.

OBJECTIVES: To utilize cytokine levels to predict sustained response (SR) to alpha interferon (IFN alpha) therapy in chronic hepatitis C patients, and to determine the relationship between serum tumor necrosis factor alpha (TNF alpha), interleukin (IL) IL 6, IL 8, IL 12, transforming growth factor beta (TGF beta 1) and the degree of liver damage as reflected by traditional markers. DESIGN AND METHODS: Serum cytokine levels were assessed using ELISA in 18 patients included in a controlled clinical trial of IFN alpha. RESULTS: Of the 18 patients, 27% were sustained responders (SR), 27% were response and relapse responders (RR), and 46% were non-responders (NR). Multivariate analysis showed that a low serum TNF alpha level and high serum IL 8 levels were independent factors associated with SR to IFN alpha therapy. Serum TNF alpha level highly correlated with viral load and genotype predictive values (p < 0.001). Therapy lowered the IL 6 and IL 12 profile. TGF beta 1 levels in serum are positively correlated with fibrinogenesis. CONCLUSIONS: IFN alpha therapy modulates immune response to hepatitis C virus, contributing to sustained response.

Adult↗
PubMed1999

Treatment of hepatitis C patients with normal aminotransferases levels.

An important subset of patients with chronic hepatitis C have normal ALT levels despite having detectable HCV RNA in serum. These patients are typically identified after donating blood and being found positive for antibody to HCV (anti-HCV). A strict definition of this patient population is needed, which should include the presence of anti-HCV, detectable HCV RNA by PCR and persistently normal ALT levels. These patients are usually asymptomatic, but on liver biopsy almost all have histologic evidence of chronic hepatitis. The histologic findings generally are mild, and cirrhosis is rare. The long-term outcome of this group of patients with chronic HCV infection is not known, but the prognosis is probably good. In small, uncontrolled trials of IFN-alpha in patients with normal ALT levels, end-of-treatment virologic responses occurred in 42% of patients, and sustained responses 6 to 12 months afterwards in 13% of patients. These rates of response are not very different from those reported in patients with elevated ALT levels. Importantly, in most studies, serum ALT levels became elevated during IFN therapy in approximately one half of patients, and levels remained elevated in some of these patients after therapy. These findings suggest that IFN-alpha therapy is not usually beneficial and may be harmful in chronic hepatitis C patients with normal ALT levels. Combination therapy with IFN and ribavirin has not been evaluated in this group of patients.

Alanine Transaminase↗
PubMed1999

[Hepatic brucelloma: 2 cases and a review of the literature].

We report two new cases of hepatic brucelloma in addition to the 22 previously reported cases in the literature. Our analysis of these cases reveals certain characteristics. Hepatic brucelloma is a rare localization that follows previously undetected acute brucellosis. Brucelloma is a result of caseification of a granulomatous reaction induced by persistent Brucella in macrophages. Clinical manifestations can mimic malignant liver tumors or pyogenic, amebic liver abscess. Diagnosis is based on the association of characteristic imaging features (central calcification and peripheral necrotic areas), positive serology and hepatic granulomas. Brucella is rarely isolated in the blood or liver. Awareness of this clinical variant can prevent unnecessary laparotomy. Treatment should begin with rifampicine (900 mg per day) and doxycyclin (200 mg per day) for 3 months. If medical treatment is unsuccessful, percutaneous or surgical drainage should be performed. A cure should be achieved in all cases.

Anti-Bacterial Agents↗
PubMed1998

Molecular cloning and characterization of tomato cDNAs encoding glutathione peroxidase-like proteins.

In Lycopersicon esculentum, two cDNAs encoding glutathione peroxidase (GPX)-like proteins were isolated, sequenced and characterized as putative phospholipid hydroperoxide:glutathione peroxidases. After mechanical stimulation (rubbing) of the plant, each GPX tomato gene was found to behave differently in terms of inducibility and tissue distribution. The accumulation of GPX transcripts suggests that reactive oxygen species are involved in the plant response to a mechanical stress.

Amino Acid Sequence↗
PubMed1998

Re-treatment with interferon alfa of patients with chronic hepatitis C.

Treatment of patients with chronic hepatitis C has had limited success because of relapses and nonresponse to interferon alfa therapy (currently the only established therapeutic agent). A retrospective study was done to determine the efficacy of re-treatment with interferon and the predictors of response in patients who failed to achieve sustained response after one standard course of interferon therapy (3 million units three times a week for 24 weeks). One hundred and eleven patients (47 relapsers and 64 nonresponders), mean age 45 years, were included in the study. Eighteen relapsers and 13 nonresponders received a higher dose (5 MU), and 11 relapsers and 6 nonresponders received a longer duration (48 weeks) of interferon therapy. The remaining patients received the same regimen as the first treatment. Eighty-one percent and 23% of relapsers and nonresponders, respectively, had an end-of-treatment response, and 19% and 3% of the corresponding patient groups had a sustained response to re-treatment. Two patients with breakthrough during their first treatment were the only nonresponders with sustained response after re-treatment. Sustained response was observed only in patients who received an increased dose or duration of interferon therapy. No predictor of sustained response was found. In conclusion, sustained response to re-treatment with interferon was only observed with augmentation of dose or duration of therapy in some relapsers and patients who had breakthrough. Established predictors of response to interferon in naive patients, in particular serum hepatitis C virus RNA and genotype, were not associated with sustained response to re-treatment.

Adult↗
PubMed1998

Predictors of sustained response to alpha interferon therapy in chronic hepatitis C.

BACKGROUND/AIMS: The aim of this study was to determine the predictors for sustained response to alpha interferon therapy in a large population of patients with chronic hepatitis C, using multivariate analysis. METHODS: Two hundred and ninety-six patients were included in four controlled trials of alpha interferon. Pretreatment serum HCV RNA levels were assessed by the branched DNA version 2.0 assay and HCV genotypes by the reverse hybridization assay (LiPA). RESULTS: Sustained responses were observed in 37%, 14% and 6% of the patients with low, medium and high pretreatment serum HCV RNA levels, respectively (p<10(-4)). Sustained responses were observed in 5%, 4%, 32% and 27% of the patients with genotype 1a, 1b, 2a and 3a, respectively (p<10(-4)). The multivariate analysis showed that a non-transfusional source of HCV infection, low serum HCV RNA levels and HCV genotypes non-1 (2a or 3a) were independent factors associated with sustained response to interferon therapy. CONCLUSION: Virological factors (low pretreatment serum HCV RNA level and HCV genotype non-1a and non-1b), when adjusted in a large population of patients, using improved technology, are the main independent predictors of sustained response to alpha interferon therapy.

Adult↗
PubMed1998

Changes in liver fibrosis at the end of alpha interferon therapy and 6 to 18 months later in patients with chronic hepatitis C: quantitative assessment by a morphometric method.

BACKGROUND/AIMS: The aims of the study were to determine, in patients with chronic hepatitis C treated with alpha interferon: (i) changes in the morphometric evaluation of liver fibrosis at the end of treatment and 6, 12 and 18 months after treatment; (ii) the predictive value of histologic lesions for the response to treatment, in particular the predictive value of morphometric evaluation of liver fibrosis. METHODS: Seventy patients with chronic hepatitis C who participated in two trials of recombinant interferon alpha 2b treatment were studied. Liver specimens were obtained before and at the end of treatment and 6, 12 or 18 months later. Histologic lesions were assessed according to the Knodell system. Quantitative study of total fibrosis and of Disse space collagen was done by the computerized automated morphometric method. RESULTS: A significant decrease in morphometric Disse space collagen was observed at the end of treatment and 6 months later. This decrease was also observed, although it was not significant, 12 and 18 months after treatment. There was no relationship between this decrease and the biochemical and virological responses or the dose of interferon. The pretreatment Knodell activity score, but not the morphometric evaluation of fibrosis, was a significant predictor of sustained response. CONCLUSION: A decrease in Disse space collagen, as assessed by the sensitive morphometric method, was observed at the end of and 6 months after treatment. This observation is consistent with an anti-fibrogenetic effect of alpha interferon. Mild or moderate histologic activity was associated with a sustained response to therapy.

Antiviral Agents↗
PubMed1997

Long-term histologic improvement and loss of detectable intrahepatic HCV RNA in patients with chronic hepatitis C and sustained response to interferon-alpha therapy.

BACKGROUND: Less than 20% of patients with chronic hepatitis C have a sustained response to interferon-alpha therapy. The long-term benefit of interferon-alpha with regard to hepatic viral clearance and histologic improvement remains unknown. OBJECTIVE: To determine the long-term biochemical, virologic, and histologic outcomes in patients with chronic hepatitis C who have a sustained response to interferon-alpha therapy. DESIGN: Prospective cohort study. SETTING: University hospital. PATIENTS: 80 patients who had chronic hepatitis C, had a sustained biochemical and virologic response to interferon-alpha therapy, and were followed for at least 12-months. MEASUREMENTS: Serum hepatitis C virus (HCV) RNA detected by polymerase chain reaction (PCR); HCV genotyping determined by line probe assay; liver histologic studies; liver HCV RNA detected by PCR on frozen liver tissue samples (in 27 patients); and repeated measurements of serum alanine aminotransferase (ALT) levels. Liver biopsy was done before treatment in all 80 patients, and at least one biopsy was done in 69 patients 1 to 6 years after treatment. RESULTS: The 80 patients had follow-up 1 to 7.6 years (mean +/- SD, 4.0 +/- 2.0 years) after interferon-alpha treatment. The follow-up period was 1, 2, 3, 4, 5, 6, and more than 6 years in 11, 13, 14, 18, 10, 12, and 2 patients, respectively, after the end of therapy. During the entire follow-up period, 93% (95% CI, 84% to 97%) of patients had persistently normal serum ALT levels. Serum HCV RNA remained undetectable in 96% (CI, 89% to 99%) of patients. A comparison of liver histologic findings before and 1 to 6.2 years after interferon-alpha treatment showed a clear improvement in 94% (CI, 83% to 99%) of patients. In 62% of patients, the last biopsy done showed normal or nearly normal histologic findings. Liver HCV RNA was detectable before treatment in all 13 patients tested and was undetectable 1 to 5 years after treatment in all 27 patients tested. CONCLUSIONS: In patients with chronic hepatitis C who have persistently normal serum ALT levels and no detectable serum HCV RNA 6 months after interferon-alpha therapy, a long-term sustained biochemical and virologic response is generally seen. This response is associated with an absence of detectable intrahepatic HCV RNA and marked histologic improvement.

Alanine Transaminase↗
PubMed1997

Influence of hepatitis G virus infection on the severity of liver disease and response to interferon-alpha in patients with chronic hepatitis C.

BACKGROUND: Dual infection with hepatitis G virus (HGV) and hepatitis C virus (HCV) is common. The effect of HGV infection on chronic hepatitis C is not well known. OBJECTIVE: To assess the prevalence of HGV infection; the effect of HGV infection on the clinical, virologic and histologic features of patients with chronic hepatitis C treated with interferon-alpha; and the influence of HGV infection on response to interferon-alpha therapy. DESIGN: Retrospective study. SETTING: A university hospital in France. PATIENTS: 228 patients with chronic hepatitis C treated with interferon-alpha (3 million U or 5 million U subcutaneously 3 times a week for 3, 6, or 12 months). MEASUREMENTS: Before initiation of treatment, serum HGV RNA and serum HCV RNA were detected with branched-DNA assays and HCV genotype was determined with a line probe assay. Serum HGV RNA and serum HCV RNA were detected by polymerase chain reaction at the end of treatment and 6 months after treatment. RESULTS: Infection with HGV was detected in 21% of patients and 32% of intravenous drug users. The median serum HGV RNA level was 33 x 10(6) genome equivalents/mL. Infection with HGV was more frequently found in men with a history of intravenous drug use and was associated with HCV genotype 3a (P = 0.02) independent of the source of infection. Serum HCV RNA levels, liver histologic findings, and response to interferon-alpha therapy did not differ between patients with and those without HGV infection. The loss of serum HGV RNA was not correlated with the biochemical response contrarily to the loss of serum HCV RNA. CONCLUSIONS: Infection with HGV occurred frequently in this sample of patients with chronic hepatitis C, especially in patients infected with HCV genotype 3a. The level of HGV viremia was high relative to the level of HCV viremia. Infection with HGV did not influence the severity of liver disease or response to interferon-alpha therapy.

Adult↗
PubMed1997

Persistence of hepatitis B virus DNA in serum and liver from patients with chronic hepatitis B after loss of HBsAg.

BACKGROUND/AIMS: The persistence of serum and liver hepatitis B virus (HBV) sequences in patients with chronic hepatitis B after loss of HBsAg has already been described. We have attempted to elucidate the significance of these HBV sequences after loss of HBsAg. METHODS: Fifteen patients were studied. We looked for serum and liver HBV DNA, using polymerase chain reaction (PCR) with different sets of primers and in situ hybridization. The sedimentation velocity of serum HBV DNA was measured on a gradient of sucrose in two patients. RESULTS: Serum HBV DNA was detected by PCR in four of the 14 patients tested at 0 months after loss of HBsAg, two patients remained HBV DNA positive until 12 months, and none was positive at 24 months. The sedimentation velocity of serum HBV DNA in sucrose was relatively similar to that of a chronic HBV carrier with active viral replication. Liver HBV DNA was demonstrated by PCR in all 15 patients and by in situ hybridization in six patients. CONCLUSIONS: Our results show that: 1) HBV DNA may persist in the serum in a minority of patients and may be associated with circulating viral particles; 2) HBV DNA persists in the liver in all patients and its extrachromosomal localization was shown by in situ hybridization technique in some cases. These results suggest the persistence of low-level HBV replication after loss of HBsAg.

Adult↗
PubMed1997

Morphological responses and molecular modifications in tomato plants after mechanical stimulation.

Study of the growth responses of Lycopersicon esculentum (Mill. cv. VFN8) to mechanical stimulation applied to a single young internode showed a rapid and sharp decrease in stem elongation and an inhibition of elongation of several internodes, indicative of information transmission in the plant. A new tomato cDNA partial clone encoding calmodulin was isolated and used to study the time course of the gene induction in response to the rubbing treatment. Northern blot analysis showed a maximum accumulation of calmodulin mRNA 2 h after mechanical stimulation, not only in the rubbed internode, but also in upper and lower internodes and in young leaves. Treatment of the plant with calcium and EGTA showed the involvement of calcium and, in particular, intracellular calcium in calmodulin gene expression and cellular response.

Amino Acid Sequence↗
PubMed1997

Effects of a mechanical stimulation of localization of annexin-like proteins in Bryonia dioica internodes.

Mechanical stimulation exerted by rubbing a young internode of Bryonia dioica plants inhibits its growth. Previous cellular and biochemical studies showed that this growth inhibition is associated with Ca(2+) redistribution and profound modifications of plasma membrane characteristics. We extracted and purified Ca(2+)-dependent phospholipid-binding proteins from B. dioica internodes. Two main proteins, p33 and p35, and other minor bands were isolated and identified as annexin-like proteins because of their biochemical properties and their cross-reactions with antibodies against maize (Zea mays L.) annexins. Rabbit antiserum was obtained by injection of B. dioica p35. This antiserum was used for the immunocytolocalization of annexin-like proteins in internode parenchyma cells. It appeared that the distribution of annexin-like proteins was different before and 30 min after the mechanical stimulation. Western analysis of proteins in membrane fractions after separation by free-flow electrophoresis showed that p35 was present in most fractions, whereas p33 appeared mainly in plasmalemma-enriched fractions after the mechanical stimulation. It is hypothesized that a subcellular redistribution of these proteins might be involved in growth inhibition by mechanical stress.

Animals↗