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Biomedical subjects

F Roudot-Thoraval

Publications and source records attributed to F Roudot-Thoraval.

At least 73 records · Page 4Linked to original sources

Prevalence of hepatitis G virus RNA in French blood donors and recipients.

BACKGROUND: Recently, cases of chronic hepatitis were linked to the presence of genomic sequences of a newly described RNA virus termed hepatitis G virus (HGV) and belonging to the Flaviviridae family. STUDY DESIGN AND METHODS: The presence of HGV RNA was searched for by polymerase chain reaction in a population of blood donors and in patients who had received multiple blood component transfusions and/or intravenous immunoglobulin (IVIG) infusions. RESULTS: Twenty-one (4.2%) of 500 donors were positive for HGV RNA as were 21 (10.7%) of 196 nonimmunosuppressed patients who had received multiple transfusions of packed red cells, 4 (8.7%) of 46 common variable immune deficiency (CVID) patients who had received only IVIG, and 22 (24.7%) of 89 bone marrow transplant (BMT) patients who had received IVIG and cellular components. The proportion of HGV-positive individuals was significantly higher in the immunosuppressed recipients (CVID and BMT patients) than in the nonimmunosuppressed patients who were multiply transfused with packed red cells (p < 0.03). The proportion of HGV-positive individuals was significantly higher in the BMT patients who had received IVIG and cellular components than in the CVID patients who had received IVIG only (p < 0.03). Eight (17.0%) of the 47 HGV-positive recipients and 48 (16.9%) of the 284 HGV-negative recipients had a serum alanine aminotransferase level higher than the upper limit of normal (nonsignificant difference). The medical history of HGV-positive donors failed to reveal a particular at-risk event. The large majority of HGV-infected patients had a normal serum alanine aminotransferase level, and the proportion of patients with elevated alanine aminotransferase was the same in HGV-positive and in HGV-negative recipients. CONCLUSION: The pathological significance of HGV infection remains unelucidated, and the classification of HGV as a new hepatitis virus was perhaps premature.

Adult↗

Myofibroblast accumulation induced by transforming growth factor-beta is involved in the pathogenesis of nasal polyps.

Myofibroblasts that express alpha-smooth muscle actin (alpha-SMA) are detected in many chronic inflammatory diseases. Transforming growth factor-beta (TGF-beta) is a potent inducer of myofibroblast accumulation in tissues. In this study, scattered myofibroblasts and TGF-beta were quantified and localized in nasal polyps (NPs) and normal nasal mucosa (NM). NPs were sampled in 16 patients during ethmoidectomy and NM was obtained from 10 control subjects during rhinoplasty. alpha-SMA and TGF-beta were detected using immunohistochemistry and the numbers of labeled cells were quantified (alpha-SMA and TGF-beta indices) and compared between NPs and NM. In eight NPs, in which the pedicle was preserved, alpha-SMA and TGF-beta were evaluated and compared in the pedicle, central, and tip areas. Finally, TGF-beta expression was compared between low (zone 1), moderate (zone 2), and high (zone 3) zones of alpha-SMA positivity. alpha-SMA and TGF-beta indices were significantly higher in NPs than in NM. In the eight selected NPs, alpha-SMA-positive cells were significantly more abundant in the pedicle than in the central and tip areas, whereas TGF-beta-positive cells were significantly more numerous in the pedicle than in the tip area. The number of TGF-beta-positive cells was significantly higher in zone 3 than in zone 1 of alpha-SMA positivity. Myofibroblasts, which are abundant in NPs but rare in NM, could be involved in the growth of NPs by inducing extracellular matrix accumulation. The local development of myofibroblasts in NPs could be controlled by TGF-beta, locally produced by inflammatory cells.

Actins↗

Influence of underfilling on breast implant deflation.

The authors report a series of 407 patients with a total of 709 saline breast implants (average follow-up, 7.1 years). In this retrospective series, the overall deflation rate was 6.6 percent (47 of 709). Initial comparison of the deflation rates for smooth (8.8 percent) versus textured (1.8 percent) implants suggested a significant difference between the implant types. However, further analysis of the data revealed that smooth implants had a longer average follow-up period and tended to have lower fill volumes. These data were re-examined using Kaplan-Meier survival analysis plots, which corrected for differences in follow-up times, and log rank tests performed to determine significance. Implant type was found to have a non-significant association with rupture rate. In contrast, the percent fill (implant fill volume per minimum recommended fill volume x 100) was significantly associated with the spontaneous ruptures; a mean difference of 13.9 percent (89.2 percent versus 103.1 percent) was found between the series of deflated implants and the nondeflated implants (p < 0.0001). These data suggest that underfilling is a major cause of deflation.

Adolescent↗

GEMHEP multicenter quality control study of PCR detection of GB virus C/hepatitis G virus RNA in serum.

PCR is, to date, the only available tool for the detection of GB virus C (GBV-C) and hepatitis G virus (HGV) RNAs. Twenty-two French laboratories participated in a quality control study to assess the sensitivity and specificity of their procedures. The panel included 13 positive controls and 7 negative controls. The laboratories used either in-house PCR techniques adapted from the literature or partly standardized commercial tests. Three laboratories performed faultlessly with the entire panel. Most laboratories had excellent specificity (100% in 20 of 22 laboratories). Sensitivity was acceptable (85 to 100%) in 15 centers and insufficient (38 to 77%) in 7. As with nonstandardized in-house PCR, the commercial assays gave discrepant performances in different laboratories. These results suggest that laboratories willing to use PCR for detection of GBV-C/HGV RNA for research or diagnostic purposes should participate in multicenter quality control trials.

Flaviviridae↗

Renal and vascular effects of C-type and atrial natriuretic peptides in humans.

C-type natriuretic peptide (CNP) may affect renal and vascular functions differently from atrial natriuretic peptide (ANP). The objective of this study was to compare the renal and vascular actions of CNP to those of ANP in normal men. CNP or ANP (0.005, 0.01, and 0.05 microg x kg(-1) x min(-1)) were given by infusion to eight healthy volunteers. CNP caused dose-dependent increases in natriuresis (U(Na)) and in the fractional excretion of sodium (FE(Na)) with no effect on diuresis (UV), renal plasma flow, and glomerular filtration rate (GFR). Fraction of filtration (FF) increased only with the 0.05 microg x kg(-1) x min(-1) CNP dose. ANP caused larger increases in U(Na), FE(Na), and FF than CNP and also increased UV at 0.01 and 0.05 microg x kg(-1) x min(-1) and GFR at 0.05 microg x kg(-1) x min(-1). Although the ANP and CNP infusions produced similar elevation in the respective peptides plasma levels, urinary and nephrogenous guanosine 3',5'-cyclic monophosphate increased less in response to CNP than to ANP. Blood pressure, forearm blood flow, plasma renin activity, and aldosterone remained unaffected during the peptides infusion. Plasma ANP increased slightly during CNP infusion. Our data indicate a higher threshold of renal response to CNP than to ANP. In contrast to ANP, CNP probably may not act as an endocrine factor in humans.

Adult↗

Evaluation of a French version of the Bath Ankylosing Spondylitis Disease Activity Index in patients with spondyloarthropathy.

OBJECTIVE: To develop a French version of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and to determine its metric properties in patients with all forms of spondyloarthropathies (SpA). METHODS: A French version of BASDAI was obtained after a translation and back-translation process. Patients fulfilling the European Spondylarthropathy Study Group or Amor criteria for SpA were included. BASDAI of Day 0, Day 1, and, when treatment was changed, Day 8, and other clinical and biological disease activity variables were recorded, along with assessment of disease activity by the physician or the patient. Scalability, reproducibility, sensitivity to change, internal consistency and redundancy, and construct validity of the index were assessed. RESULTS: We studied 293 patients. Good scalability, reproducibility, construct, and internal validity were observed for BASDAI. Sensitivity to change could not be assessed. CONCLUSION: The French version of BASDAI exhibited good metric properties in patients with all forms of SpA, confirming its utility in further clinical research in SpA. However, sensitivity to changes due to drug therapy remains to be assessed.

Adult↗

Increased epithelial cell proliferation in nasal polyps.

OBJECTIVE: To detect, quantify, and compare respiratory epithelial cell proliferation in nasal mucosa and polyps from patients with nasal polyposis. DESIGN: Cohort study. SETTING: Patients and samples were selected at the Hôpital Intercommunal de Créteil (France). Flow cytofluorometry and immunohistochemistry were performed at Hôpitaux Tenon and Mondor (Université Paris [France] VI et XII). PATIENTS: Twenty-one patients undergoing endoscopic ethmoidectomy for treatment of nasal polyposis. METHODS: In 10 cases, epithelial cells were removed from frozen inferior turbinate mucosa and polyps by mechanical disaggregation and were then analyzed by flow cytofluorometry, providing the cell DNA content (propidium iodide labeling) and the percentage of S-phase cells. In 11 cases, inferior turbinate mucosa and polyps were fixed in formaldehyde and embedded in paraffin. Proliferating cell nuclear antigen expression in the epithelium was quantified by immunohistochemistry; a proliferating cell nuclear antigen index was calculated for each sample in the basal area, suprabasal area, and full height of the epithelium. RESULTS: All cell populations studied were diploid, and percentages of S-phrase cells were significantly higher in nasal polyps than in mucosa. Proliferating cell nuclear antigen indexes were significantly higher in nasal polyps than in the suprabasal area and full height of the mucosal epithelium. CONCLUSION: Cell proliferation is increased in epithelium from nasal polyps. Epithelial damage caused by inflammatory mediators could induce this increased cell proliferation via epithelial repair processes. Inflammatory cells could up-regulate epithelial cell proliferation by secreting growth factors.

Cell Division↗

Seroprevalence of hepatitis A virus infection among sewage workers in the Parisian area, France.

Sewers are an ideal environment to be occupationally exposed to viral hepatitis A (HAV) infection, because of high frequency and ability of the virus to remain viable for prolonged periods in sewage. However, data on the occupational risk of HAV infection among sewage workers is not well documented. In a cross sectional study comparing sewage workers (n = 155) to those not occupationally exposed to it (n = 70), we found a non significant increase in HAV seropositivity among sewage workers of 12.9% (p = 0.07). The prevalence of HAV antibody was significantly associated with duration of occupational exposure to sewage (p < 0.015), stay in HAV endemic areas (p < 0.03), age (p < 0.001), and number of siblings (p < 0.03). A stepwise logistic regression analysis gave an adjusted odds ratio for HAV seropositivity 2.15 fold greater in sewage workers compared to those not occupationally exposed to it. So, although there was no significant difference in the prevalence of HAV antibody between sewage workers and others, exposure to sewage was an independent risk factor for HAV seropositivity, and this raises the question of whether it is necessary to vaccinate sewage workers against viral hepatitis A.

Adult↗

A histopathological study of the effects of 6-month versus 12-month interferon alpha-2b therapy in chronic hepatitis C.

BACKGROUND/AIMS: Interferon therapy has been shown to have beneficial effects in chronic hepatitis C, but the optimal duration of treatment has not been clearly defined. The aims of this study were: (a) to perform a detailed histological comparison of the effects of a 6-month and a 12-month treatment using the Knodell score as well as a recently proposed grid of analysis, (b) to determine possible histological predictive factors of response to therapy, and (c) to attempt to relate histological and biochemical modifications. METHODS: Liver biopsies obtained before and 18 months after beginning of treatment were therefore compared in 26 patients treated for 6 months, and in 34 patients treated for 12 months. RESULTS: Six months of treatment induced a significant decrease in periportal (p = 0.02) and intralobular (p = 0.004) hepatocyte necrosis. The same items were improved in the 12-month-treated patients but, in addition, portal inflammation (p = 0.01), bile duct lesions (p = 0.03), lymphoid aggregates (p = 0.002) and fibrosis (p = 0.008) were also improved, according to the Knodell score. Low scores for fibrosis, steatosis and cholangiolar proliferation on the pretreatment liver biopsy could be considered predictive factors for alanine aminotransferase normalization at 6 months. There was no relationship between biochemical response and modification of fibrosis. CONCLUSION: Our results suggest that: (a) a decrease in fibrosis might be detected only after a 12-month interferon treatment, and (b) initial fibrosis, cholangiolar proliferation and steatosis are predictive of a lack of biochemical response. The absence of a relation between biochemical response and evolution of fibrosis implies that the evaluation of treatments in chronic hepatitis C should always include a detailed histopathological study.

Alanine Transaminase↗

Quantitation of passively acquired human immunodeficiency virus (HIV) antibodies in AIDS patients transfused with a plasma that is rich in HIV antibodies.

BACKGROUND: Passive immunotherapy in human immunodeficiency virus (HIV) infection is based on transfusions of plasma that is rich in HIV antibodies. STUDY DESIGN AND METHODS: To verify whether the clearance of transfused antibodies will maintain an elevated titer of specific antibodies between biweekly transfusions of plasma, the titers of anti-HIV-1 in plasma and in transfusion recipients were measured. Samples from 12 recipients were analyzed by automated scanning of Western blot, before transfusion and at Days 2, 7, and 14 after transfusion. RESULTS: The p24 antibody became detectable or higher than the baseline after transfusion and remained detectable until the second transfusion. Anti-p24 titers were variable and dependent on the antibody titer of the transfused plasma and the baseline p24 antigen titer. CONCLUSION: Biweekly transfusion of plasma with a high anti-HIV titer maintains a high anti-p24 titer between transfusions in AIDS patients treated with passive immunotherapy.

Acquired Immunodeficiency Syndrome↗

Factors affecting treatment responses to interferon-alpha in chronic hepatitis C.

Parameters have been studied to predict responses to interferon (IFN) therapy for chronic hepatitis C, but the definition of a response, the times at which responses were assessed, and the pretreatment parameters considered differ markedly from study to study. Thus, 113 patients with chronic hepatitis C were treated 3-6 months with 3 MU of IFN-alpha 2a three times a week and assessed for pretreatment parameters predictive of responses to IFN. In a multivariate analysis, a biochemical response (normal aminotransferase activity) at the end of treatment was significantly associated with low body weight, normal gamma-glutamyl transpeptidase activity, and a pretreatment hepatitis C virus (HCV) genotype other than 1. Six months after the end of treatment, a low virus burden and a lack of anti-HCV IgM core antibodies were independently associated with sustained virologic response (i.e., normal aminotransferase activity and HCV RNA negativity). Therefore, these pretreatment parameters should be taken into account when individual treatment protocols are designed.

Adult↗

Epithelial cell proliferation in nasal polyps could be up-regulated by platelet-derived growth factor.

The modifications of epithelial differentiation and proliferation observed in nasal polyps (NP) could be related to local secretion of growth factors, among which platelet-derived growth factor (PDGF) could play a key role. We therefore prospectively studied, by immunohistochemistry, proliferating cell nuclear antigen (PCNA, an S-phase cell marker), PDGF, and CD-68 (activated macrophages marker) expression in NP and inferior turbinate mucosa (NM) in 11 patients. Our data show that PCNA and PDGF expression are increased in NP epithelium, while CD-68 expression is increased in NP epithelium and lamina propria when compared to NM. Increased local PDGF secretion by numerous activated macrophages could therefore be involved in epithelial cell proliferation up-regulation in NP. PDGF could also be involved in the pathogenesis of NP via its connective tissue remodeling actions.

Antigens, CD↗

Effect of alpha interferon (IFN-alpha) on 2'-5' oligoadenylate synthetase activity in peripheral blood mononuclear cells of patients with chronic hepatitis C: relationship to the antiviral effect of IFN-alpha.

Alpha interferon (IFN-alpha) is, to date, the only treatment with proven efficacy in patients with chronic hepatitis C. However, less than 15% of the patients have a sustained response to IFN-alpha. Interferon acts through the induction of various cellular enzymes. Among them, the 2'-5' oligoadenylate synthetase (2-5OAS) is (at least in part) responsible for a direct antiviral effect of IFN-alpha. The aim of this study was to determine whether basal and IFN-alpha-induced in vivo and in vitro 2-5OAS activities measured in peripheral blood mononuclear cells predict biochemical and virological responses to IFN-alpha in patients with chronic hepatitis C. 2-5OAS activity in peripheral blood mononuclear cells and the antiviral effect of IFN-alpha were studied in 36 patients with chronic hepatitis C (27 men and 9 women; mean age, 44.7 years). Basal in vivo 2-5OAS activity (mean +/- standard error of the mean) was 4.41 +/- 0.69 nmol/10(6) cells. It was significantly induced at month 3 of IFN-alpha therapy (18.07 +/- 2.74 nmol/10(6) cells; P = 0.0001). No significant differences were found in basal in vivo 2-5OAS activities, in IFN-alpha-induced/basal in vitro 2-5OAS activity ratios, in IFN-alpha-induced in vivo 2-5OAS activities, and in IFN-alpha-induced/basal in vivo 2-5OAS activity ratios between the patients with and without a biochemical response (normal alanine aminotransferase activity in serum) or a virological response (normal alanine aminotransferase activity in serum and negative hepatitis C virus RNA detection) at any step of the study. At month 3 of therapy, p69, which is considered to be the active isoform of 2-5OAS, was induced, as demonstrated by Western blot (immunoblot) analysis in 50% of the patients, and induction of the p100 isoform was observed in 70% of the patients. No significant relationship with the response to IFN-alpha therapy was observed. Our results suggest that a deficiency of the IFN-alpha-dependent 2-5OAS system, which could be genetically determined, is unlikely to be responsible for the failure to achieve biochemical and virological responses to IFN-alpha therapy in patients with chronic hepatitis C.

2',5'-Oligoadenylate Synthetase↗

Extrahepatic immunologic manifestations in chronic hepatitis C and hepatitis C virus serotypes.

OBJECTIVE: To determine, using a serotyping assay, whether the occurrence of extrahepatic immunologic disorders in patients with chronic hepatitis C is dependent on hepatitis C virus serotype. DESIGN: Prospective study. SETTING: Liver unit and virology laboratory of a university hospital. PATIENTS: 59 consecutive patients with chronic hepatitis C. MEASUREMENTS: Hepatitis C virus serotype was determined using a recently developed immunoenzymatic assay that detects antibodies directed to serotype-specific immunodominant epitopes. Cryoglobulin, rheumatoid factor, and numerous antitissue antibodies were sought. Biopsies of labial salivary glands were done in 49 of the 59 patients. RESULTS: Prevalence was 59% for serotype 1, 10% for serotype 2, 12% for serotype 3, and 3% for mixed infection. Fifteen percent of patients could not be serotyped. Cryoglobulinemia was found in 36% of patients and rheumatoid factor was found in the serum of 71%. At least one antitissue antibody was found in the serum of 41% of patients; salivary gland biopsy showed lymphocytic capillaritis in 49% of patients. These immunologic abnormalities were seen in patients infected with any of the three serotypes, and prevalences of the abnormalities did not differ significantly among patients infected with different serotypes. CONCLUSIONS: We confirm that the prevalence of extrahepatic immunologic abnormalities is high in patients with chronic hepatitis C. These abnormalities may occur in patients infected with any of the three major hepatitis C virus serotypes now present in developed countries.

Adolescent↗

Significance of anti-hepatitis C virus core IgM antibodies in patients with chronic hepatitis C.

Antihepatitis C virus (HCV) IgM antibodies were found in patients with both acute and chronic hepatitis C. The aims of the study were to determine the significance, in terms of liver disease and virological parameters, of anti-HCV core IgM antibodies in the serum of patients with chronic hepatitis C, and the possible relationship between the presence of these antibodies before treatment and biochemical and virological responses to interferon therapy. Sixty-one patients with chronic hepatitis C were studied. Tests for serum anti-HCV core IgM antibodies were carried out before treatment. The patients received 3 mega units of interferon alpha-2a subcutaneously thrice weekly for at least 3 months (6 months when alanine aminotransferase activity was normal at month 3). A biochemical response to interferon therapy was defined as normal alanine aminotransferase activity at the end of treatment (month 6: biochemical response) and 6 months later (month 12: sustained biochemical response). A sustained virological response was defined as serum HCV RNA negativity by a polymerase chain reaction-based detection method (PCR) in patients with normal alanine aminotransferase at month 12. Anti-HCV core IgM antibodies were detected in 28 of the 61 patients (46%). The prevalence of these antibodies was significantly higher in patients infected with HCV genotype 1 (including subtypes 1a and 1b) than in patients infected with other genotypes (including 2a and 3a) (57% vs. 17%; P < 0.01). No significant difference was found between IgM-positive and IgM-negative patients as regards the mean age, sex ratio, serum alanine aminotransferase and gamma-glutamyl transpeptidase activities, the prevalence of cirrhosis in liver biopsy specimens, detection of HCV RNA by PCR, and quantitation by branched DNA assay. At month 6 of interferon therapy, normal alanine aminotransferase activity was significantly more frequent in IgM-negative than in IgM-positive patients (52% vs. 21%, respectively; P < 0.02). At month 12, normal alanine aminotransferase activity and PCR negativity were significantly more frequent in IgM-negative than in IgM-positive patients (18% vs. 0%, P < 0.04). It is concluded that anti-HCV core IgM antibodies in serum are significantly more frequent in patients infected by HCV type 1 than by other types. This suggests that their overall prevalence in patients with chronic hepatitis C in industrialized countries, where HCV type 1 accounts for the majority of infections, would be of the order of 50%, that anti-HCV core IgM antibodies are not associated with characteristic features of liver disease, and that their presence before treatment is associated with a failure of interferon alpha therapy to clear the virus.

Adolescent↗

Activity of the interferon-induced 2',5'-oligoadenylate synthetase in patients with chronic hepatitis C.

The interferon-induced 2',5'-oligoadenylate synthetase (2-5OAS) is responsible, at least in part, for the antiviral state established in cells in response to viral infections. The purpose of this work was to study the relationship between hepatitis C virus (HCV) infection and 2-5OAS in patients with chronic hepatitis C. Peripheral blood mononuclear cells (PBMC) of 27 patients with chronic hepatitis C were investigated, as well as PBMC of 10 control subjects. Then, the patients were treated with 3 mu interferon-alpha 2a three times per week. At month 3 of therapy, PBMC were sampled. Of the total PBMC samples obtained, half were used for determination of in vivo 2-5OAS activity. The remaining cells were cultured for 24 h in either the absence or presence of 500 U/ml of interferon-alpha 2a for the determination of in vitro 2-5OAS activity. The mean basal in vivo 2-5OAS activities were 3.6 +/- 2.8 nmol/10(6) cells in patients versus 1.6 +/- 1.1 nmol/10(6) cells in controls (p < 0.01). Basal in vivo 2-5OAS activity did not correlate with mean HCV viremia, quantified by a "branched DNA"-based assay. Before treatment, interferon-alpha was detected in the serum of 2 patients in 27. After a 24 h culture of PBMC in the presence of interferon, in vitro 2-5OAS activity was significantly induced in the PBMC of both the patients and the controls. However, in vitro induction of 2-5OAS activity was significantly lower in the PBMC of the patients than in the PBMC of the controls (p < 0.01). At month 3 therapy, in vivo 2-5OAS activity was significantly induced (20.5 +/- 17.9; p < 0.0001). In vitro IFN inductions of 2-5OAS activity in PBMC before treatment and at month 3 of therapy were not significantly different. In conclusion, in vivo 2-5OAS activity is significantly induced in patients with chronic hepatitis C, but endogenously produced interferon-alpha does not seem to be involved. Chronic induction of 2-5OAS activity results in a decreased sensitivity of PBMC to exogenous interferon induction. Whether this phenomenon plays a role in the resistance of chronic hepatitis C to interferon therapy remains uncertain.

2',5'-Oligoadenylate Synthetase↗