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Biomedical subjects

M Baud

Publications and source records attributed to M Baud.

At least 19 recordsLinked to original sources
PubMed1998

Tenoxicam, a non-steroid anti-inflammatory drug, is unable to increase the response rate in patients with chronic hepatitis C treated by alpha interferon.

The purpose of this study is to compare a combination of interferon (IFN)-alpha2a (Roferon) + Tenoxicam with IFN-alpha2a alone in the treatment of chronic hepatitis C. This prospective, randomized double-blind study included 149 patients, all of whom were diagnosed with active chronic hepatitis C but non-cirrhotic (ALT > or = 1.5 upper limit of normal, anti-hepatitis C virus (HCV) positive by enzyme-linked immunosorbant assay2 and RIBA3). The patients were randomized in two groups, as follows: G1 (n = 76): IFNalpha2a 3 million units times per week during 6 months + placebo; and G2 (n = 73): IFNalpha2a 3 million units three times per week + Tenoxicam (20 mg/day) during 6 months. Alanine aminotransferase (ALT) and HCV RNA were determined before and at months 6 and 12 of treatment. 2'5' oligoadenylate synthetase activity (2'5' AS) was dosed in mononuclear cells before and at 3-month treatment intervals in 28 patients. Liver biopsy was performed before and 6 months after the end of therapy. Parameters were similar before therapy for both groups. Biochemical and virological responses were similar for both groups at month 6 (49.3% vs. 42.9% and 43.3% vs. 38.3%, respectively) and month 12 (28.3% vs. 23.8% and 17.2% vs. 17.5%, respectively). HCV RNA level significantly decreased in both groups at month 6, with no difference whatever the therapy; however, the HCV RNA level returned to initial values at month 12 and was the only significant prognostic factor of a sustained response. No peak of 2'5' AS activity was observed during treatment in patients with dual therapy. A histological improvement was also noted in both groups without difference, regardless of therapy. The percentage of adverse events was identical for both groups. Paracetamol intake, assessed in 80 patients, was 49.1 g per 6 months in the G1 group and 22.5 g per 6 months in the G2 group (not significant). In conclusion, the non-steroid anti-inflammatory drug, Tenoxicam, does not increase IFNalpha efficacy in the treatment of chronic hepatitis C. This combination is well tolerated and partially lowers Paracetamol intake, but not preexisting alpha-IFN adverse events.

2',5'-Oligoadenylate Synthetase↗
PubMed1998

Characteristics of patients with dual infection by hepatitis B and C viruses.

BACKGROUND/AIMS: The purpose of this study was to compare the epidemiological, biochemical, virological and histological characteristics of patients with chronic hepatitis B and C with those of patients suffering from chronic hepatitis C alone. METHODS: Twenty-three patients with chronic hepatitis C, who were anti-HCV positive and HBs antigen positive, were studied and subdivided into two groups according to the presence or absence of HBV DNA replication. They were compared to 69 age- and sex-matched patients with chronic hepatitis who were anti-HCV positive and HBs antigen negative. All patients were HCV RNA positive by PCR, anti-HIV negative and anti-HDV negative. HBV DNA and HCV RNA were detected in serum by means of a branched DNA assay and PCR. The HCV serotypes were determined by the Chiron Riba HCV serotyping SIA technique. The histological characteristics included the Knodell score. RESULTS: Epidemiological, biochemical and virological parameters were not different between the two groups. Only the prevalence of cirrhosis was greater in chronic hepatitis B and C patients than in patients with chronic hepatitis C alone (p = 0.01). Among chronic hepatitis B and C patients, HCV RNA level was significantly lower in HBV DNA positive than in HBV DNA negative patients (p = 0.01). Indeed, histological lesions were more severe in HBV DNA positive than in HBV DNA negative patients, including prevalence of cirrhosis (p = 0.01), Knodell score (p = 0.05) and, among the latter, piecemeal necrosis (p = 0.01) and fibrosis (p = 0.05). The characteristics of patients with dual infection did not differ according to the mode of contamination and duration of HBV disease, except for a shorter duration in patients contaminated by drug abuse than in other patients. CONCLUSIONS: These results suggest that HBV DNA replication inhibits HCV RNA replication in patients with chronic active hepatitis B and C but increases the severity of histological lesions.

Adult↗
PubMed1998

Role of anti-interferon antibodies in breakthrough occurrence during alpha 2a and 2b therapy in patients with chronic hepatitis C.

BACKGROUND/AIMS: Alpha interferon induces aminotransferase normalization in about 50% of patients with chronic viral hepatitis C. However, some patients who initially respond experience a relapse during the treatment period (breakthrough phenomenon). The aim of this study was to evaluate the prevalence of breakthrough and its relationship with the emergence of neutralizing anti-interferon antibodies. METHODS: We studied 172 patients with histologically proven chronic hepatitis C, treated with interferon alpha 2a or 2b 3 mega units three times a week for 6 months. For each patient, HCV RNA level (polymerase chain reaction and bDNA) and anti-interferon antibodies dosage were determined during therapy. RESULTS: Among 84 patients with initial response, 13 (15.5%) experienced breakthrough. The kinetics of alanine aminotransferase and HCV RNA levels were strongly correlated, suggesting that breakthrough is not due to a random alanine aminotransferase fluctuation during treatment, but to the reappearance of viral replication. Neutralizing anti-interferon antibodies emergence was observed in 38.5% in patients with breakthrough, as compared to 9.0% and 2.8% of non-responder and complete-responder patients, respectively (p<0.0005). By multivariate analysis, the only factor predictive of breakthrough was the emergence of neutralizing anti-interferon antibodies 3 months after the onset of therapy. CONCLUSION: Our results suggest that the emergence of neutralizing anti-interferon antibodies during treatment may explain breakthrough in about one third of cases. Other causes may also be responsible for this phenomenon and they remain to be determined.

Adult↗
PubMed1998

Prevalence and significance of anticardiolipin, anti-beta2 glycoprotein I and anti-prothrombin antibodies in chronic hepatitis C.

Antiphospholipid antibodies have been demonstrated in chronic hepatitis C, but their clinical and pathogenetic significance remains elusive. We prospectively studied 115 patients (85 men, mean age 36.9 years) with chronic hepatitis C without cirrhosis and treated by alpha-interferon (alpha-IFN). Antiphospholipid determinations comprised anticardiolipin (ACA), anti-beta2-glycoprotein I and anti-prothrombin antibodies of the IgG and IgM classes. At entry, 24 patients (21%) were found to possess low to moderate ACA levels (18 IgG, two IgM and four both isotypes) compared with only 4/115 age- and sex-matched control subjects (3.5% P=0.001). ACA positivity rate increased to 31% (P=0.01) after a 6-month course of alpha-IFN treatment. In contrast, the prevalence of anti-beta2-glycoprotein I and anti-prothrombin antibodies was not significantly different from controls at either time point. The presence of ACA correlated with that of antinuclear antibodies (P=0.0002), but was not associated with parameters such as histological activity, viral burden and response to alpha-IFN, nor with a history of thrombosis or pregnancy loss. However, a non-significant trend of higher incidence of mild thrombocytopenia among ACA-positive patients was observed. We conclude that low-titre ACA positivity is a common finding in patients with chronic hepatitis C, especially following alpha-IFN treatment, but does not select a category with different clinical features. These data are in keeping with the absence of associated anti-beta2GPI and anti-prothrombin antibodies, and do not support a role for HCV infection in the pathogenesis of the antiphospholipid syndrome.

Adult↗
PubMed1998

Post-pubescent to mature fathers: increase in progeny quality?

In the mouse, offspring born from mature fathers exhibit better behavioural performances (for spontaneous activity in both sex and learning capacity in males) than those born from post-pubescent fathers. These behavioural variations are not accompanied by other obvious modifications. They could correspond to what has been observed in man relating to the results in a psychometric test undergone by male progeny born from very young to mature fathers. These data and those which show a decrease in mental performance in rats and human males born from mature to senescent fathers suggest the participation of some genetic factors in these phenomena.

Aging↗
PubMed1997

Acute respiratory distress syndrome due to falciparum malaria in a pregnant woman.

We report the case of a pregnant woman (29th week), living in a Paris suburb, about 20 miles from an international airport. She presented with septic shock and severe acute respiratory distress syndrome (ARDS). A few parasitized erythrocytes were discovered in a hemorrhagic bronchoalveolar lavage (BAL), specimen and many were found on examination of the placenta after a caesarean section had been performed. The patient's condition dramatically improved once given quinine therapy. This is an uncommon case on account of: (1) the unusual clinical course with no organ failure but ARDS, (2) the unusual way the diagnosis was made, (3) the very unusual way the patient became contaminated (airport malaria), (4) the pregnant condition of the patient.

Antimalarials↗
PubMed1997

[Value of high-dose interferon-alpha in chronic viral hepatitis C patients non-responder to a 1st treatment. Pilot study prospective and randomized trial].

OBJECTIVES: The aim of this study was to evaluate the efficacy of two different doses of alpha interferon (IFN) for retreatment in chronic hepatitis C patients who were non responders to initial treatment by IFN at a dose of 3 MIU TIW for 6 months. METHODS: This open, pilot, prospective, randomized and bicentric study included patients with biopsy-proven chronic hepatitis C. Non response was defined as serum ALT levels > 2 upper limit of normal for the entire first treatment period, HCV RNA positivity by PCR at the end of the first treatment period, and the persistence of histologically-proven chronic active hepatitis after the first treatment period. Patients were randomized into two groups: group I received IFN alpha 2b 10 MIU TIW for 2 months, then 6 MIU TIW for 4 months, group 2 received IFN alpha 2b 6 MIU TIW for 6 months. RESULTS: Twenty three patients (17 male, 6 female, mean age: 38.7 +/- 9.1 years) were included: 14 were randomized in group 1 and 9 in group 2. Both groups were similar for the main clinical, biochemical, and histological variables. At the end of retreatment, 2 patients (14.2%) had biochemical and virological response in group 1 and 4 in group 2 (44.4%) (non significant). Only one biochemical and virological sustained response was observed in group 2 (11.1%) (non significant). There was no difference between the groups for complete and sustained response. An overall statistical significant improvement of Knodell score was observed (7.8 +/- 3.8 vs 9.6 +/- 3.2, P < 0.02) in the 18 patients who had a second biopsy 6 months after the end of therapy, while the Knodell score did not change at the end of the first treatment period. This improvement was statistically significant in group 2 (5.4 +/- 3.0 vs 9.2 +/- 9.5 before treatment, P < 0.02) and concerned intralobular necrosis (P < 0.05). The Metavir index did not change. The number of side-effects was similar in both groups. CONCLUSIONS: These results suggest that histological improvement may be obtained after IFN retreatment in some patients who are non-responders to the first treatment, despite an absence of biochemical and/or virological response.

Adult↗
PubMed1996

Efficacy and toxicity of mitomycin, ifosfamide, and cisplatin (MIP) in patients with inoperable non-small cell lung cancer.

Seventy-two patients with advanced stage IIIB (42%) or stage IV (58%) non-small cell lung cancer (median age 57 years, Karnofsky PS 60-100) were treated with mitomycin C (6 mg/m2, day 1), ifosfamide (1500 mg/m2, days 1-3), and cisplatin (30 mg/m2, days 1-3) every 4 weeks. The objective response rate was 37% in the overall population; 50% in stage IIIB patients and 29% in stage IV patients. Twenty four patients achieved partial response (33%) and three patients achieved complete response. Despite this relatively high objective response rate, the overall median survival time was 32 weeks. The median survival was significantly better in stage IIIB patients (55 weeks) than in stage IV patients (25 weeks) (P = 0.003). MIP regimen was permanently suspended in 14 patients because of toxic events. Seventeen patients developed grade III or IV febrile neutropenia and two patients died from sepsis. Two patients experienced acute mitomycin peumonitis. Despite increased doses of cisplatin and ifosfamide, compared with the original description for MIC chemotherapy, with probably higher toxicity, no apparent increased response rate or median survival was observed in this study. The MIP regimen could be tested in a randomized trial in comparison with other administration plans in a comparable population.

Adult↗
PubMed1995

Chromosome 18 analysis by fluorescence in situ hybridization (FISH) in human blastomeres of abnormal embryos after in vitro fertilization (IVF) attempt.

We performed fluorescence in situ hybridization (FISH) with a chromosome 18-specific probe on human abnormal cleaved embryos, fertilized either by two spermatozoa and exhibiting three pronuclei (3 PN) or normally fertilized and exhibiting two pronuclei (2 PN) with subsequent severe fragmentation and/or blocking. The aim of the study was to evaluate the incidence of chromosome 18 anomalies among these embryos in order to evaluate the FISH efficiency on such material and to obtain more precise and complete data than those obtained with classical cytogenetic analysis. For the 3 PN cleaved embryos, FISH confirmed the frequent regulation towards diploidy (25 per cent) and the high frequency of mosaics (53 per cent). For the 2 PN blocked or damaged embryos, FISH permitted chromosome evaluation, which was otherwise impossible with classical cytogenetic techniques: we also found a high mosaic frequency (45 per cent) with these embryos. If this frequency were the same for normally developing embryos, it would be a major obstacle to the reliability of either chromosomal or genetic preimplantation diagnosis.

Blastomeres↗
PubMed1995

Phase I-II and pharmacokinetic study of a new fotemustine schedule in advanced non-small cell lung cancer.

UNLABELLED: Fotemustine, a new nitrosourea derivative has already demonstrated activity in non-small cell lung cancer (NSCLC). In order to improve its therapeutic index, we designed a protocol in which Fotemustine was delivered with dose escalation on 3 consecutive days as induction therapy followed by a 5-week rest period. Maintenance therapy consisted of 100 mg/m2 once every 3 weeks. Pharmacokinetic data were assessed during this Phase I-II study and reported here. PATIENTS AND METHODS: Nineteen patients with metastatic (17) or locally advanced (2) NSCLC were included in the present study. Ten of those with metastatic disease had brain metastases and 15 had previously received chemotherapy. Fotemustine was given at 50 mg/m2 on day 1-2-3 (group 1: four patients), 75 mg/m2 on day 1-2-3 (group 2: 16 patients including two who had already received 50 mg/m2) and 100 mg/m2 on day 1-2-3 (group 3: one patient). RESULTS: The maximal tolerated dose was 75 mg/m2 on day 1-2-3 (total cumulated dose 225 mg/m2). At this dose level, we observed 25% of Grade 3-4 neutropenia and 31% of Grade 3-4 thrombocytopenia. One patient died of pulmonary infection during aplasia. No other significant toxicity occurred. Of the 17 evaluable patients, one obtained a PR lasting 6 months in group 2 and 1 PR lasting 3 months in group 3. No significant difference was noted in the AUC between days 1, 2 or 3 in any of the seven patients in whom a pharmacokinetic study of Fotemustine was performed. CONCLUSION: Administered on 3 consecutive days, Fotemustine seems to be less effective and more toxic than other schedules tested in NSCLC. Despite the quality of the two responses observed, this protocol has been discontinued and the standard administration on days 1 and 8 remains the schedule of choice in NSCLC.

Adult↗
PubMed1994

Measurement of CO2 response with the breath-by-breath automatic acquisition of the breathing pattern and occlusion pressure.

OBJECTIVE: Our objective is to present a methodology for the automated acquisition and storage of BP and P0.1 during a CO2 rebreathing test. METHODS: The system consists of a microcomputer with additional circuits and an automatic electronically controlled valve to occlude the inspiratory airway. Data collection and data processing are separate programs. Airway pressure and flow are digitized at a 100-Hz rate, while PETCO2 is determined and P0.1 is measured on a breath-by-breath basis. Off-line processing calculates the BP variables, generates a correlation matrix (VE/PETCO2, TTOT/PETCO2, TI/PETCO2, TE/PETCO2, [VT/TI]/PETCO2, [TI/TTOT]/PETCO2, P0.1/PETCO2), and edits graphic data. The accuracy of the volume and pressure measurements was tested by comparing known volumes provided by a syringe (n = 100) and a series of pressures controlled by a water manometer (n = 41) on the one hand, with volumes and pressures measured by the device. The accuracy of the time intervals and P0.1 was assessed by comparing in 10 healthy subjects the values measured manually on a graphic recording with those provided by the device (n = 170). RESULTS: Volumes:Vmeasured = 0.99 x Vcontrolled, r = 0.99, p < 0.001. Pressures:Pmeasured = 0.97 x Pcontrolled + 0.09, r = 0.98, p < 0.001. Inspiratory time:TIautomatic = 0.91 x TIgraphic + 0.22, r = 0.93, p < 0.001. Expiratory time:TEautomatic = 0.93 x TEgraphic + 0.34, r = 0.95, p < 0.001. Occlusion pressure:P0.1automatic = 0.95 x P0.1graphic + 0.62, r = 0.94, p < 0.001. Reproducibility was assumed to be represented by the intraindividual coefficient of variation of the CO2 response. The comparison of an automatic breath-to-breath method with a graphic manual recording revealed significantly less variability with the former (VE/PETCO2: 15.2 +/- 4.5% vs 22.5 +/- 6.3%, p < 0.01; P0.1/PETCO2:8.3 +/- 4.3% vs 19.7 +/- 7.2%, p < 0.001; [VT/TI]/PETCO2:9.1 +/- 3.5% vs 14.5 +/- 5.3%, p < 0.05). CONCLUSION: Our automated acquisition and storage of waveforms and breath-by-breath determination of BP and P0.1 provide an easy and thorough analysis of the respiratory response to CO2 and decrease the variability of the results.

Anesthesia, Closed-Circuit↗
PubMed1994

Oral immunization with bacterial extracts for protection against acute bronchitis in elderly institutionalized patients with chronic bronchitis.

Acute bronchitis is a major source of morbidity in elderly patients. The purpose of this study was to assess the preventive effects of oral immunisation with a bacterial extract. Three hundred and fifty four patients with chronic bronchitis, living in institutions for the elderly (aged > 65 yrs), were included in a randomized, placebo-controlled, double-blind study. The purpose of the study was to assess preventive effects of OM-85 BV (an immunostimulating agent consisting of lyophilized fractions of eight of the most common pathogens isolated in respiratory tract infections) against acute lower respiratory tract infections. Two hundred and ninety patients completed the study (143 taking placebo and 147 taking OM-85 BV). There was a 28% reduction in the number of lower respiratory tract infections in the patients treated with OM-85 BV; this was entirely due to 40% reduction in the number of episodes of acute bronchitis (p < 0.01), with no difference in the number of episodes of pneumonia and bronchopneumonia. A larger number of patients in the OM-85 BV group were free of acute bronchitis throughout the 6 month study period (96 vs 69) and there was a 28% reduction in the number of antibiotic prescriptions in the OM-85 BV treated group. These results suggest that OM-85 BV has a protective effect against acute bronchitis in elderly patients living in institutions.

Aged↗
PubMed1993

A rapid, simple method for calculating equilibrium constants and antibody site concentrations from dilution curves alone.

A rapid new practical method for calculating both the antibody-antigen equilibrium constant and the antibody concentration from antibody dilution curve data alone is described. This method is faster than the inhibition curve method for evaluating a humoral immune response. It is particularly suitable for monitoring the immune response of an immunization program. The response is assessed as an immunization index, Abi*Ka. This index is more exact than the antibody titer obtained from dilution curves and independent of the specific activity of the labelled molecule and total activity used in the assay. The method was used to monitor the production of a monoclonal antibody to the sulphide peptide leucotriene including immunization, cloning and purification.

Algorithms↗
PubMed1993

[Preventive effect of an immunomodulator, OM-85 BV, on acute exacerbations of chronic bronchitis in elderly patients. Preliminary results at six months in 291 patients].

Three hundred fifty six patients aged 65 years or more (mean age 81.8 years) who were suffering from chronic bronchitis were included in a double-blind trial against placebo to assess the preventative effect of OM-85 BV against acute exacerbations of chronic bronchitis. OM-85 BV is an immunostimulant composed of lyophilised factions of 8 bacteria which are most frequently encountered during the course of respiratory tract infections. 291 patients completed the study. In the group treated by OM-85 BV, a significant increase in the number of patients with no episode of acute bronchitis was noted (96 versus 71, p = 0.006). There was a 38.8% reduction in the absolute numbers of episodes of acute bronchitis and a 33% reduction in the number of prescriptions for antibiotics, however there was no difference in the number of pneumonias and bronchopneumonias. These results show the protective effect of OM-85 BV against bronchial superinfections in a large population of elderly patients suffering from chronic bronchitis.

Acute Disease↗
PubMed1992

Effects of doxapram on hypercapnic response during weaning from mechanical ventilation in COPD patients.

Failure of weaning from mechanical ventilation in COPD patients is often related to diaphragmatic fatigue. Whether there is a central respiratory drive fatigue and a reserve of excitability is still debated. The purpose of this study was to analyze the following in 13 COPD patients weaned from mechanical ventilation: (1) ventilatory (VE/PETCO2) and neuromuscular (P0.1/PETCO2) response to hypercapnia; (2) the maximum reserve capacity measured through changes in the VE/PETCO2 and P0.1/PETCO2 slopes after doxapram (DXP) infusion, which, given during the test, allows measurement of the maximum response capacity to overstimulation; and (3) analyze the influence of these changes on the outcome of weaning. The results show a variable P0.1/PETCO2 response and a low VE/PETCO2. DXP infusion does not change the slopes of these relations but increases the end-expiratory volume (delta FRCd); (p less than 0.02). Since there was no change in the VE/PETCO2, P0.1/PETCO2, and delta FRC values with or without DXP, there was no excitability reserve in patients who were successfully weaned. When weaning failed, DXP did not change VE/PETCO2 and P0.1/PETCO2 slope, but delta FRCd was greater the delta FRC (p less than 0.001). The excitability reserve in these patients leads to an increase in end-expiratory volume, probably worsening the diaphragm dysfunction.

Aged↗