[Hepatitis C virus infection and pregnancy].
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Female↗
Biomedical subjects
C Laffont
Publications and source records attributed to C Laffont.
Changing of hepatitis C virus genotype patterns in France at the beginning of the third millenium: The GEMHEP GenoCII Study.
This cross-sectional study aimed to investigate, during a short period between 2000 and 2001, in a large population of patients with chronic hepatitis C, the epidemiological characteristics of hepatitis C virus (HCV) genotypes in France. Data from 26 referral centres, corresponding to 1769 patients with chronic hepatitis C were collected consecutively during a 6-month period. HCV genotyping in the 5'-non-coding region (NCR) was performed in each center using the line probe assay (LiPA, in 63% of cases), sequencing (25%) or primer-specific polymerase chain reaction (PCR) (12%). HCV genotypes 1a, 1b, 2, 3, 4, 5, non-subtyped 1 and mixed infection were found in 18, 27, 9, 21, 9, 3, 11 and 1% of our population, respectively. HCV genotype distribution was associated with gender, age, source and duration of infection, alanine aminotransferase (ALT) levels, cirrhosis, alcohol consumption, hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection. In multivariate analysis, only the source of infection was the independent factor significantly associated with genotype (P = 0.0001). In conclusion, this study shows a changing pattern of HCV genotypes in France, with i.v. drug abuse as the major risk factor, an increase of genotype 4, and to a lesser extent 1a and 5, and a decrease of genotypes 1b and 2. The modification of the HCV genotype pattern in France in the next 10 years may require new therapeutic strategies, and further survey studies.
Adult↗
The severity of liver fibrosis is associated with high leptin levels in chronic hepatitis C.
Recent attention has focused on the liver profibrogenic role of leptin in animal models. The purpose of this study was to evaluate the role of leptin and TNF-alpha in the severity of liver fibrosis in patients with chronic hepatitis C (CHC). We used a radioimmunoassay to determine serum leptin concentrations in 77 consecutive patients with CHC and 22 healthy controls. Leptin was correlated with liver histological (METAVIR) and metabolic indices. Sixty five patients had none to moderate liver fibrosis (F0-F2) and twelve severe fibrosis (F3-F4). Steatosis was observed in all but 27 patients. Leptin was significantly increased in patients compared with controls and was significantly more elevated in females both in patients and controls. The age, age at infection, prothrombin index, body mass index (BMI), triglycerides, glycaemia, ferritin, leptin and TNF-alpha, were associated with severe fibrosis. Steatosis was significantly more pronounced in patients with severe than those without or moderate fibrosis (P = 0.04). Only leptin was significantly and independently associated with severe fibrosis (OR = 1.2, CI 95%: 1.1-1.4, P = 0.03). Leptin was significantly associated with BMI (r = 0.64, P < 0.001) and glycaemia (r = 0.43, P < 0.001). Significant correlations were found between steatosis and BMI (r = 0.30, P < 0.01) and glycaemia (r = 0.30, P < 0.01). In patients with CHC and higher BMI and glycaemia levels, the severity of liver fibrosis is associated with serum leptin. TNF-alpha is a putative candidate involved in the mechanism.
Adolescent↗
Fatigue is associated with high circulating leptin levels in chronic hepatitis C.
BACKGROUND AND AIMS: Fatigue is a frequent and disabling symptom reported by patients with chronic hepatitis C (CHC). Its mechanism is poorly understood. Recent attention has focused on the role of leptin and energy expenditure in CHC. Our aims were to analyse fatigue in CHC and to determine its relationship with disease activity, resting energy expenditure (REE), circulating leptin, and tumour necrosis factor alpha (TNF-alpha). METHODS: Seventy eight CHC patients, 22 healthy controls, and 13 primary biliary cirrhosis (PBC) patients underwent measurements of REE, body composition, leptin, and TNF-alpha. All subjects completed the fatigue impact scale (FIS) questionnaire. A liver biopsy and viral load measurements were performed in all patients. RESULTS: Thirty eight of 78 CHC patients considered fatigue the worst or initial symptom of their disease. The fatigue score of patients was significantly higher than that of controls (53.2 (40.1) v 17.7 (16.9); p<0.0001) and was more pronounced in females (p=0.003). Leptin was increased significantly in CHC patients compared with controls (15.4 (20.7) v 6.4 (4.1) ng/ml; p<0.05). In CHC patients, the fatigue score correlated significantly with leptin corrected for fat mass (r=0.30, p=0.01). This correlation increased when the physical domain of fatigue was included (r=0.39, p=0.0009). Furthermore, a similar positive correlation was found in PBC patients (r=0.56, p=0.04). No correlation was found between fatigue and age, REE, liver function tests, viral load, or the METAVIR score in CHC patients. CONCLUSIONS: Fatigue is present in CHC patients and is more pronounced in females. The FIS questionnaire is clinically relevant and may be useful for future therapeutic trials aimed at reducing fatigue. Fatigue may be partly mediated by leptin.
Adult↗
Effects of 1-year interferon-alpha 2a treatment in patients with chronic hepatitis C and persistently normal transaminase activity.
BACKGROUND: Certain chronic hepatitis C carriers have persistently normal transaminase activity. The aims of this study were to determine the virologic and histologic effects of 1 year of interferon-alpha treatment in such patients. METHODS: Thirty-one patients were followed up in our Liver Unit. Eleven accepted interferon-alpha therapy; the 20 others were not treated and served as controls. Interferon-alpha, 3 MU, was given thrice weekly for 1 year. Serum was examined for hepatitis C virus (HCV)-RNA before, at the end of, and 6 months after treatment. Liver biopsy was performed 6 months after the cessation of treatment in 10 of 11 treated patients (one refused biopsy) and after a mean of 30.6+/-22.7 months in the 20 untreated patients. RESULTS: At the end of follow-up two of the treated patients had undetectable serum HCV-RNA and five had increased alanine aminotransferase (ALAT) values. In contrast, only one of the untreated patients had abnormal ALAT activity. All 20 untreated patients were constantly viremic. No significant histologic improvement was observed in the treated patients evaluated by means of post-treatment liver biopsy. The mean annual progression rate of fibrosis was very slow and similar in the treated and untreated patients (0.09 (range, 0-0.62) versus 0.07 (range, 0-0.60) fibrosis units). CONCLUSIONS: One year of interferon-alpha treatment can suppress HCV-RNA in patients with chronic hepatitis C and persistently normal ALAT values followed up over long periods. The rate of fibrosis progression in such patients is very slow, and therapeutic strategies should take this fact into account. Antiviral treatment is debated for patients without fibrosis in initial biopsy specimens.
Adult↗
Second generation of the automated Cobas Amplicor HCV assay improves sensitivity of hepatitis C virus RNA detection and yields results that are more clinically relevant.
The first and second generations of the Cobas Amplicor HCV assay were compared among patients at risk of hepatitis C virus (HCV) infection. The second-generation test was found to be of greater sensitivity and of good specificity among clinical specimens containing HCV RNA of different genotypes. Finally, this new test is shown to predict the outcome of interferon therapy better.
Hepacivirus↗
Hepatitis G and C viruses respond to interferon-alpha with different virologic kinetics.
The aim of this work was to specify the time course of response to interferon (IFN) of hepatitis G virus (HGV) and hepatitis C virus (HCV) in coinfected individuals. A group of 33 patients, undergoing 12 months of IFN therapy for chronic hepatitis C, was screened for the presence of both HGV and HCV RNAs to select seven coinfected patients. Spontaneous recovery from HGV infection was excluded through the detection of antibodies to the envelope-2 protein of HGV and HCV isolates were genotyped. Within three months of treatment, we found that HGV RNA was transiently cleared in 6/7 patients, but the rate of long-term favorable response was very low (1/7). In addition, considering the same individuals separately, it was shown that HGV and HCV responded to IFN with different kinetics in 5/7 patients. Taken together, these results underscore the importance of the virological basis of the resistance to IFN treatment.
Antiviral Agents↗
Cloning and expression of cDNA for a human Gal(beta1-3)GalNAc alpha2,3-sialyltransferase from the CEM T-cell line.
Complementary DNA encoding a human Gal(beta1-3)GalNAc alpha2,3-sialyltransferase type II (hST3Gal II) was cloned from a CEM T-cell cDNA library using a 23-base oligonucleotide probe. The sequence of this probe was established on the basis of a slightly divergent sialylmotif L that was obtained by polymerase chain reaction with degenerate oligonucleotide primers based on the conserved sialylmotif L of mammalian Gal(beta1-3)GalNAc alpha2,3-sialyltransferases. It was thus confirmed that a short oligonucleotide probe may be sensitive and highly specific. The nucleotide and amino acid sequences of hST3Gal II show, respectively, 56.3% and 49.3% similarity to hST3Gal I [Kitagawa, H. & Paulson, J. C. (1994) J. Biol. Chem. 269, 17872-17878] and 88.1% and 93.7% similarity to murine ST3Gal II [Lee, Y. C., Kojima, N., Wada, E., Kurosawa, N., Nakaoka, T., Hamamoto, T. & Tsuji, S. (1994) J. Biol. Chem. 269, 10028-10033]. hST3Gal II mRNA was highly expressed in heart, liver, skeletal muscle and various lymphoid tissues but not in brain and kidney. A soluble form of hST3Gal II expressed in COS-7 cells was tested in vitro for substrate specificity and kinetic properties. Asialofetuin and asialo-bovine submaxillary mucin appeared better substrates for hST3Gal II than for its murine counterpart as previously reported [Kojima, N., Lee, Y.-C., Hamamoto, T., Kurosawa, N. & Tsuji, S. (1994) Biochemistry 33, 5772-5776]. In previous studies, we have shown hyposialylation of O-glycans attached to two major lymphocyte CD43 and CD45 cell surface molecules in human-immunodeficiency-virus-1(HIV-1)-infected T-cell lines. Since comparable levels of hST3Gal I and hST3Gal II mRNA and enzymatic activity were observed in parental and HIV-1-infected CEM T-cell lysates, the sialylation defect associated with HIV infection of this cell line is probably due to a mechanism different from a simple altered catalytic activity of these sialyltransferases.
Amino Acid Sequence↗
Phenotyping of intrahepatic and peripheral blood lymphocytes in patients with chronic hepatitis C.
The host immune responses have been suggested to play a role in liver injury occurring in patients with chronic hepatitis C. In order to explore the relationship between the relative proportions of intrahepatic and peripheral blood lymphocytes (IHL, PBL), the levels of viremia, and the histological hepatitis activity score, three-color fluorescence-activated cytometric analysis was performed for 36 patients with chronic hepatitis C and six control subjects without chronic hepatitis. The liver biopsy was performed before any antiviral therapy. Each liver specimen was divided into two parts: one for histological examination and one for immunological analysis. Tricolor CD45 was used to improve "lymphogating." Fluorescein isothiocyanate- or phycoerythrin-conjugated monoclonal antibodies with specificity for CD3, CD4, CD8, and CD20 (lymphocyte subpopulations), for CD69 (activated lymphocytes), and for CD16/56 (natural killer cells) were used. The livers of patients with chronic hepatitis C contained a greater proportion of CD4+ lymphocytes that exhibited marked expression of CD69 than in control subjects (20.7 +/- 7.3% vs 10.2 +/- 4.6%, P = 0.027). Moreover, in patients with chronic hepatitis C, the proportion of CD4+ IHL correlated with the histological hepatitis activity evaluated by the Knodell score (r = 0.48, P = 0.004). No correlation was found between the percentage of CD4+ IHL and the level of viremia or transaminase activities. Our findings clearly indicate that a cellular immune response does take place in HCV-infected livers and could thus contribute to the outcome of hepatitis C virus infection.
Adult↗
[Methicillin-resistant Staphylococcus aureus infection].
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Cross Infection↗
Guillain-Barré syndrome associated with acute Q fever.
Several bacterial and viral agents have been implicated in the pathogenesis of the Guillain-Barré syndrome, an acquired immune-mediated disorder. A case of Guillain-Barré syndrome associated with acute Q fever is described. Coxiella burnetii should therefore be added to the list of microorganisms capable of inducing the Guillain-Barré syndrome.
Adult↗
[Epidemiologic study of hepatitis B virus and human immunodeficiency virus transmission among dental surgeons in the Alpes Maritimes region].
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Dentists↗
[Broncho-alveolar lavage in HIV-1 seropositive children].
Sixteen bronchoalveolar lavages (BAL) were performed in 15 children with HIV1 seropositivity, 12 of them being infected by HIV1. BAL was performed during episodes of acute pneumonitis with respiratory distress (group I: three cases) or without severity (group II: five cases), or in the presence of asymptomatic radiological pulmonary abnormalities (group III: seven cases). A specific diagnosis of infection was obtained in five cases of acute pneumonitis and 12 micro-organisms were identified by BAL: three cytomegaloviruses, three respiratory syncytial viruses, two Pneumocytis carinii, one Haemophilus influenzae, one Herpes simplex virus type 1, one Escherichia coli and one group A streptococcus. In three cases two micro-organisms were simultaneously identified. Cytological examination showed a high proportion of polymorphonuclear leukocytes in cases of acute pneumonitis (group II) and alveolar lymphocytosis in clinically asymptomatic children with radiological pulmonary abnormalities (group III). BAL appears to be a reliable tool for the investigation of pulmonary infections in children with HIV1 seropositivity. In addition it has the advantage of revealing latent cytological abnormalities in these patients.
Bronchoalveolar Lavage Fluid↗
[Determination of antibiotype by a computer program. Epidemiological significance and antibiogram-identification correlates].
By means of a computer program disk diffusion diameter were analysed and an antibiotic susceptibility code (antibiotype) was determined for enterobacteriaceae. This code was a 6 figure-number. Each figure summarised susceptibility (susceptible or resistant) to 3 antibiotics. Thus a 18 serial antibiotics was necessary to calculate the 6 figure-code. At least following antibiotics were chosen for their characteristic behavior: amoxycillin, ticarcillin, amoxycillin + clavulanic acid, cephalothin, ticarcillin + clavulanic acid, cefotaxime, gentamycin, tobramycin, amikacin, nalidixic acid, pefloxacin, ciprofloxacin, fosfomycin and colistin. This code allowed three kind of utilisation: epidemiology by comparing biochemical and susceptibility patterns of same isolated species; laboratory control: a data base with main antibiotic susceptibility patterns for each species allowed a rapid compatibility control of biochemical identification with antibiogram. An inconsistent result lead to a checking of biochemical and susceptibility tests or to record a new code in a file to a further enrichment of the data base. Impression of a message depending of the code for a therapeutic purpose.
Drug Resistance, Microbial↗
[In vitro activity of fusidic acid in combination with various antibiotics against Staphylococcus epidermidis].
In vitro antibacterial activity of fusidic acid (FUC) in combination with cefotaxime (CTX), imipenem (IMP), gentamicin (GEN), amikacin (AKN), rifampin (RIF), fosfomycin (FOS), vancomycin, pefloxacin (PEF) was studied against 19 presumably pathogen meti-R Staphylococcus epidermidis strains. The study was carried out by means of a microtiter checkerboard method (FICs index, 19 strains) and killing-curves (3 strains). FUC x GEN, FUC x AKN and FUC x IMP combinations were found synergistic with achievable therapeutic concentrations for IMP (MIC in the combination less than 1 microgram/ml) but with higher concentrations for AKN and GEN (greater than or equal to 8 micrograms/ml). FUC x PEF combinations were regularly antagonistic. FUC x RIF, and FUC x FOS combinations showed a modal FIC greater than or equal to 4 but were found respectively additive and synergistic with killing-curve method. Remaining FUC combinations results were variable. FUC resistant mutant frequency, studied for 3 S. epidermidis strains, was similar as S. aureus one's (0.5.10(-7) a 2.5.10(-8)).
Drug Resistance, Microbial↗
[Urinary Corynebacterium group D2 infections. A hospital epidemic and antibiotic sensitivity].
An outbreak of Corynebacterium group D2 urinary tract infections was recently observed at Nice CHR. These infections were characterized by alkaline urine. The five first cases were reported in the same department and the ten other cases were latter observed in different departments. Age average was 79 and all patients had either an intra-vesical catheter of a urinary collector. Among samples of material tested, only one gave a positive culture. The 15 isolates showed a similar identification and antibiotic phenotype. These strains presented a multiple antibiotic resistance: resistance to beta-lactams, aminoglycosides (except streptomycin), erythromycin, chloramphenicol, tetracyclines. All strains were susceptible to rifampin, pristinamycin, fusidic acid and vancomycin.
Aged↗
[Isolation of LAV/HTLV III from tears of patients with the ARC syndrome].
Isolation of Human Immunodeficiency Virus (HIV) was attempted from the tears of seven patients with ARC. For two of these patients the fluid from cell cultures showed significant reverse transcriptase activity. One strain was maintained on C.E.M. (T lymphocytes cell line). Indirect fixed cell immuno fluorescence and Western Blot tests have shown this strain to be a HIV. This result confirms other already published data. Although there is no evidence of transmission through tears, the presence of the virus should not be forgotten.
AIDS-Related Complex↗
[Thrombophlebitis on intravenous cardiac stimulator electrodes].
The main feature of venous thrombosis on endocardial pacing electrodes are described with reference to 7 cases: the incidence is relatively low (0.4 to 4 p. 100) and the diagnosis obvious in the typical axillary-subclavian form associated with pain, oedema and collateral circulation. Diagnosis is mainly clinical and rehoplethysmography, rather than venography with its potential complications, is the complementary investigation of choice. Internal jugular, innominate vein, vena cava and intracardiac thrombosis may also occur. The vena cava syndromes are observed mainly in patients with multiple electrodes. Atrial or ventricular endocavitary thrombosis may give rise to hemodynamic signs of cardiac failure or to thromboembolism which may be fatal. Operational technique is an important factor in the etiology of early thrombosis especially when the approach vein is ligatured. In the late period, the loss of venous mobility due to the presence of a foreign body makes the vessel susceptible to compression in the cervico-brachial region. The mainstay of treatment is anticoagulation with intravenous or subcutaneous heparin with mobilisation and elevation of the affected arm. Fibrinolysis may be indicated in superior vena cava syndromes (case no 1), the results being better when therapy is instituted early on. Long term anticoagulation is not indicated (case no 7) and may even be dangerous in elderly patients with multiple electrodes.
Aged↗