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Biomedical subjects

S Chevret

Publications and source records attributed to S Chevret.

At least 181 records · Page 10Linked to original sources

Prognostic value of an elevated CD8 lymphocyte count in HIV infection. Results of a prospective study of 152 asymptomatic HIV-positive individuals.

OBJECTIVE: To evaluate the prognostic value of an elevated CD8 lymphocyte count in the early stages of HIV infection. DESIGN: A prospective study ongoing since January 1986. METHODS: One hundred and fifty-two asymptomatic HIV-positive individuals with a CD4 lymphocyte count > 400 x 10(6)/l at enrollment were included. Disease progression was defined as a CD4 count < 200 x 10(6)/l. RESULTS: During the follow-up period, CD4 count decreased in 33 individuals; CD8 count increased to > 1500 x 10(6)/l in 38 individuals and doubled in 35. The risk of a decreasing CD4 count was estimated to be 1.7-fold higher, although not significantly so, after the elevation of the CD8 count to > 1500 x 10(6)/l than before or in the absence of such an increase. However, this predictive value disappeared when five baseline parameters found to predict the outcome (neopterin, beta 2-microglobulin, p24 antigen, anti-p18 antibody and immunoglobulin A) were adjusted. CONCLUSION: Elevated CD8 count appears to be a weak marker for disease progression.

Adult↗

A new approach to estimating AIDS incubation times: results in homosexual infected men.

STUDY OBJECTIVE: The aim was to develop a new approach for estimating the incubation period of acquired immunodeficiency syndrome (AIDS), based on age distributions. DESIGN: Incubation period was expressed as the difference between age at time of diagnosis and age at time of contamination. Assuming independence between age at time of infection and incubation period, the age distribution of newly diagnosed AIDS cases is thus the convolution product between the distributions of the age of freshly infected patients and of the incubation times. AIDS incubation time can therefore be estimated from the age distribution of newly HIV infected subjects and newly diagnosed AIDS cases. SUBJECTS: Subjects were 2220 AIDS cases diagnosed until 1987, reported to the Ministry of Health, France, and 172 subjects discovered to be HIV-1 seropositive during a blood donation in Paris between August 1985 and July 1988. In both groups, the only known risk factor was homosexuality. MAIN RESULTS: The estimated median incubation time was 9.9 years (90% CI 9.0-10.9 years). Confidence intervals were narrow, even when taking into account the uncertainty in serodetection delay (90% CI 6.7-13.5 years). CONCLUSIONS: The incubation estimate is as accurate as previous estimates based on other models. This technique could therefore be applied to other risk groups.

Acquired Immunodeficiency Syndrome↗

Evaluation of residual disease in B-cell chronic lymphocytic leukemia patients in clinical and bone-marrow remission using CD5-CD19 markers and PCR study of gene rearrangements.

We evaluated minimal residual disease (MRD) in 23 CD5 + B-chronic lymphocytic leukemia (CLL) patients who achieved clinico-hematological remission confirmed by bone-marrow biopsy. MRD was evaluated by dual marker analysis flow-cytometry using CD5 and CD19 markers, and by the study of Ig heavy chain gene rearrangements using the fast polymerase chain reaction (PCR). According to our laboratory conditions patients were considered to be in complete phenotypic remission when total CD19+ cells were < 25% and the ratio of CD5 + CD19 + /CD19 + cells was < 25%. According to these strict criteria only 9 of the 23 patients were in complete phenotypic remission. In order to evaluate the sensitivity of the above method, PCR analysis of the configuration of the Ig heavy chain gene region was performed in 12 of these patients. Five of 7 patients in complete phenotypic remission retained a detectable monoclonal rearrangement of the Ig heavy chain gene. For the remaining 5 patients in partial phenotypic remission, only one failed to show a monoclonal band and this is probably explained by the presence of an unusual gene rearrangement. In conclusion, this study suggests that PCR is more sensitive than dual marker flow-cytometry for evaluation of residual disease and that it is indeed possible to achieve complete remission at the molecular level, in B-CLL. Nevertheless, we suggest a word of caution as this was a retrospective study, and samples were not assessed before treatment. Thus the possibility that apparent molecular remission might correspond to unusual gene rearrangements cannot be completely excluded in these cases.

Adult↗

[Long-term survival and prognostic factors in stage II-III multiple myeloma treated with conventional chemotherapy].

In this retrospective study, survival and prognostic factors were analysed in 65 patients with stage II-III multiple myeloma with osteolytic lesions. Multiple myeloma was diagnosed from 1976 to 1984, and patients were treated with conventional chemotherapy. The response rate to initial chemotherapy was 46%. The median survival time was 31 months. The 10-year survival rate was 10%. Four variables were individually prognostic: response to initial chemotherapy, bone marrow plasma cell percentage, the Durie and Salmon staging system, a biological staging system derived from Durie and Salmon's biological criteria regardless of bone lesions. In the multivariate analysis, only two prognostic variables were retained, namely the response to chemotherapy and the biological staging system. No prognostic value was observed for the extent of osteolytic lesions. This study suggests that, in conventionally treated multiple myeloma, long-term survival has improved compared with the previous decade. It also indicates that the extent of osteolytic lesions has little value for the definition of high-risk myeloma.

Adult↗

The role of autologous blood stem cells in support of high-dose therapy for multiple myeloma.

During the last few years, high-dose therapy with hemopoietic stem cell support has become a well-admitted therapeutic option for young patients with MM. The role of allogeneic or autologous graft and of blood rather than bone marrow as the source of hemopoietic stem cells must be further investigated. Autologous PBSC transplantation has, however, both practical and theoretic advantages over allogeneic and autologous BMT: (1) It can be applied to most patients, especially if blood stem cells are collected early in the course of therapy. (2) It usually induces relatively rapid hematologic reconstitution. (3) In comparison with autologous BMT, it appears to minimize the hazard of the reinfusion of malignant cells.

Combined Modality Therapy↗

[Therapeutic maintenance and tolerance of sulfasalazine in rheumatoid polyarthritis. Retrospective study of 95 patients].

This retrospective study evaluated treatment with sulfasalazine (SAS) in a mean dosage of 2.1 g/day in 95 patients with rheumatoid arthritis (RA) who were followed-up for 3 months to 4 years. Mean disease duration was 7 years; 79 patients had previously received at least one disease-modifying drug. Four per cent of patients were lost to follow-up. Mean duration of treatment was 15 months (3 weeks-50 months). Treatment continuation rates were 57% at one year, 40% at two years, and 26% at three years. Reasons for discontinuation of SAS included adverse effects (n = 24), inefficacy (n = 33), and death unrelated to SAS therapy (n = 2). In four patients, SAS was discontinued within three months of the first dose because of a severe adverse effect (diffuse erythematous rash, diffuse bullous rash, hepatitis with jaundice, agranulocytosis). SAS-induced biologic markers for lupus were seen in one patient. Furthermore, 12% of evaluable patients developed antinuclear antibodies during SAS therapy. The SAS treatment continuation rate was higher (p = 0.05) among patients under 40 years of age (n = 18) than among older patients. This difference was due to a correlation between age and tolerance with less SAS-induced side effects in patients under 40 years of age (p = 0.03). The SAS treatment continuation rate was unrelated to the duration of rheumatoid arthritis or number of previous maintenance treatments. This study suggests that rheumatoid arthritis patients under 40 years of age exhibit better tolerance to SAS therapy.

Adolescent↗

Methods for dose finding studies in cancer clinical trials: a review and results of a Monte Carlo study.

We discuss some of the statistical approaches to the design and analysis of phase I clinical trials in cancer. An attempt is made to identify the issues, particular to this type of trial, that should be addressed by an appropriate methodology. A brief review of schemes currently in use is provided together with our views of the extent to which any particular scheme addresses the main issues. Some simulations are provided together with graphical illustration of the operating characteristics of the particular methods. It appears that the continual reassessment method is preferable to other contending schemes.

Antineoplastic Agents↗

Efficacy of coronary sinus cardioplegia in patients with complete coronary artery occlusions.

Myocardial areas distal to complete coronary artery occlusions are poorly protected by antegrade cardioplegia. We assessed the effects of coronary sinus cardioplegia in 30 patients undergoing bypass operations and at high risk of cardioplegic maldistribution because of the following anatomical patterns of coronary artery disease: critical (greater than or equal to 50%) stenosis of the left main trunk with total occlusion of the right coronary artery (16 patients) or critical (greater than or equal to 70%) stenosis of the right coronary artery with total occlusion of the left anterior descending (11 patients) or circumflex artery (3 patients). After induction of arrest through the aorta, coronary sinus cardioplegia was given intermittently during the cross-clamp period at a flow rate of 100 mL/min. Intraoperatively, occluded arteries were consistently found to be filled with the retrogradely infused solution. One patient died early postoperatively of low cardiac output and a second patient died later during his hospital stay, presumably of an arrhythmia. At autopsy, none of them had pathological evidence of inadequate myocardial protection. One patient sustained a myocardial infarction and 3 others required inotropes for more than 24 hours postoperatively. Postoperative values for right and left stroke volume indices were not significantly different from prebypass levels. Overall, these results are consistent with the occurrence of limited intraoperative ischemic damage and, by inference, suggest the efficacy of the coronary sinus route in preserving myocardial areas supplied by completely occluded coronary arteries and, hence, in jeopardy of inadequate cardioplegia delivery.

Aged↗

Activity of clarithromycin against Mycobacterium avium infection in patients with the acquired immune deficiency syndrome. A controlled clinical trial.

Disseminated Mycobacterium avium infection is common in patients with acquired immune deficiency syndrome (AIDS), but no drug studies have been reported establishing antimicrobial activity against this organism in a controlled, randomized trial. Clarithromycin, a new macrolide, has activity against M. avium in vitro and in animals, but it has not been studied in humans. In this randomized, double-blind, placebo-controlled trial, we measured the ability of clarithromycin to reduce M. avium bacteremia in patients with AIDS and disseminated infection. Of 23 patients initially enrolled, 15 men with late-stage AIDS qualified for the study. One group received clarithromycin alone for 6 wk, then placebo plus rifampin, isoniazid, ethambutol, and clofazimine for 6 wk. The other group received placebo alone, then clarithromycin plus the other four drugs. Colony-forming units (CFU) of M. avium per milliliter of blood were determined by quantitative cultures taken at baseline and every 2 wk thereafter. Minimum inhibitory concentration of clarithromycin for 90% of the strains isolated from patients at baseline, as measured on 7H11 agar at pH 6.6, was 8 micrograms/ml. Eight eligible patients with initial positive cultures who were initially receiving clarithromycin alone had marked declines in blood M. avium CFU; in six cases, CFU decreased to zero. When seven patients were switched to placebo plus the other four drugs, CFU rose in four patients and remained undetectable in three. The five eligible patients initially treated with placebo had progressive CFU increases; when three were switched to clarithromycin plus the four drugs, their CFU declined.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

High dose chemoradiotherapy and autologous blood stem cell transplantation in multiple myeloma.

We report the results of peripheral blood stem cell (PBSC) collection performed after priming with a semi-intensive CHOP regimen in 70 patients with aggressive multiple myeloma (MM). Forty-one of the 44 previously untreated patients compared to 17 of the 26 patients with a refractory disease yielded stem cells enough for autotransplantation. Phenotypic and genotypic studies of collected mononuclear cells, even performed after depletion of monocytes and/or of T lymphocytes, did not reveal contamination by tumor plasma cells or clonal B cell precursors in any studied case. Forty-eight of the 58 patients with successful PBSC collection have been presently treated by high dose therapy followed by autologous blood stem cell transplantation (ABSCT). Among the 43 patients who received a regimen including total body irradiation, four died within six months after the autograft. All remainders responded and most often achieved an impressive tumor mass reduction. Ten relapsed and four died from disease progression. Nine to 70 months (median: 35 months) after blood stem cell collection, 29 patients are either in apparent complete remission or with a state of stable residual disease, most often minimal. Blood stem cell autograft was successful in all evaluable patients and the kinetic of hematologic recovery was roughly related to the amount of reinfused CFU-GM (2.1 to 50 x 10(4)/kg). Median delays for granulocytes greater than 500/mm3 and platelets greater than 25,000/mm3 were 15 days and 20 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Cardiovascular risks induced by estrogens prescribed at low doses. 208 years of observation--137 patients].

The cardiovascular risk induced by oestrogen treatment appears to be minimal when oestrogens are prescribed at low doses (daily dose less than 3 mg/day) and when this drug is not prescribed in patients with a history of cardiovascular disease. The Prostatic Cancer Cooperative Study Group compared the course of 137 patients treated by oestrogens with a French male population matched for age: ten accidents were observed versus nine expected and one death was observed versus 3 expected. By selecting patients, oestrogens can therefore still be part of the range of treatments available for advanced prostatic cancer.

Aged↗

[Prevalence of HIV-1, HIV-2 and HTLV-1 infections. Experience in a Parisian center for sexually transmitted diseases].

Human immunodeficiency virus (HIV) infection is, to a great extent, a sexually transmitted disease (STD). Its diffusion among the heterosexual population is still limited. STD treatment centres are particularly well organized to watch this diffusion. At the STD centre of the Saint-Louis hospital, Paris, we conducted a 6-week prospective study concerning the systematic detection of HIV-1 infection in 240 consecutive female out-patients in 1988, and in 504 male out-patients in 1989. The results obtained were as follow: 5/240 women (2.1 percent) and 19/504 men (3.8 percent) were seropositive for HIV-1. Out of these 24 subjects, 15 did not know they were seropositive. Predictive factors for seropositivity were male homosexuality, addiction to heroin and, in women, drug addicts as sex partners. Altogether, 23 of the 24 seropositive subjects had the classical risk factors for HIV-1 infection. None of the 744 subjects in this study were HIV-2 seropositive, and only 1 out of 504 men was HTLV-1 seropositive. We conclude that the prevalence of HIV-1 infection was high in our centre, and this prompts us to suggest that the serological test should be proposed to all out-patients and that patient's education and preventive measures should be organized by STD centres, even though the infection is still limited to patients at a particularly high risk (drug addicts, homosexuals, country of origin).

Adult↗

Prognostic factors of acute non lymphoblastic leukemia in children and adults. Results from two multicentric trials (705 patients).

705 children and adults patients with de novo acute nonlymphoblastic leukemia were entered from 1981 to 1989 into 2 prospectives multicenter trials: 01AM81 and 01AM86. They received an intensive induction course with Rubidazone 200 mg/sqm/day x 4 days and cytosine arabinoside 200 mg/sqm/day x 7 days, then 3 consolidation courses at outpatients, and a maintenance treatment. Total duration of therapy was 3 years. The overall complete remission rate was 80%. The median overall survival time was 19 months and the 5-year survival rate is 26%. The median remission duration for the 568 remitters was 18 months and the 5-year first remission rate is 30%. Prognostic factors for the remission rate were age, initial leukocytosis, FAB subtype. Prognostic factors for remission duration were the delay until CR, initial leukocytosis and karyotype.

Adolescent↗

Methodological aspects of a clinical trial in chronic lymphocytic leukemia: necessity to develop new biostatistical methods.

The CLL protocol allowed a better understanding of the natural history of Chronic Lymphocytic Leukemia and an assessment of several treatment strategies. From the point of view of biostatistical research, it raised several important problems. In this paper, we show the interest of applying sequential methods, particularly the triangular test. Other biostatistical problems raised by the CLL 80 protocol are still not, or only partially, resolved. They include taking into account prior belief about treatment benefit in sample size calculations, using surrogate endpoints, developing methods to take into account the causes of death, to analyse repeated measurements, and to assess and compare staging systems.

Biometry↗

[Invasive cancer of the uterine cervix in young women: retrospective study of 236 cases].

The study of cases treated between 1970 and 1984 at the Institut Curie, in women aged 40 years and under, was undertaken in order to determine the influence of age on prognosis. The incidence of these cases was stable throughout the 15 years study period as was the very high incidence of earlier cases: 84.5%. Earlier cases were treated with combined radiotherapy and surgery and advanced cases with radiotherapy alone. Overall survival rate was 75% at 5 years, 60% at 10 and 15 years: but 85% for the 36-40 years of age group, 74% for the 30-35 years of age group and 67% for women aged 29 and less. Five year survival rate for operated cases is the same for the 36-40 age group as for all age patients, according to the lymph node status. In contrast, it was 85% in the N-younger group, and 30% for those patients with lymph node involvement. In conclusion, from our study it appears that the overall survival rate for women of 36 years and less, and mainly 29 years and less, is significantly lower than that for older women, and that their prognosis is especially poor in the case of lymph node involvement.

Adenocarcinoma↗