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Biomedical subjects

C Chastang

Publications and source records attributed to C Chastang.

At least 163 records · Page 9Linked to original sources

In vitro effects of folate inhibitors on Toxoplasma gondii.

Three sulfonamides and four dihydrofolate reductase inhibitors were tested alone and in combination to determine their in vitro effects on two strains of Toxoplasma gondii grown in MRC5 fibroblast tissue culture. Toxoplasma growth was quantitated by an enzyme immunoassay performed directly on the fixed cultures, and linear regression models were used to quantify the relationship between the optical density values generated by the enzyme-linked immunosorbent assay and the concentrations of the antimicrobial agents in the culture medium. The cytopathic effects of antimicrobial agents on T. gondii were examined in Giemsa-stained cultures. Sulfonamides and dihydrofolate reductase inhibitors exhibited similar patterns of inhibition, consisting of an important increase of the inhibitory effect within a narrow range of concentrations. Sulfadiazine, sulfamethoxazole, and sulfisoxazole were all found to have important inhibitory effects on T. gondii; the 50% inhibitory concentrations estimated from the regression models were 2.5 micrograms/ml for sulfadiazine, 1.1 micrograms/ml for sulfamethoxazole, and 6.4 micrograms/ml for sulfisoxazole. This inhibition of growth was associated with a reduction of the number of parasitized cells and intracellular parasites that were morphologically normal. With dihydrofolate reductase inhibitors, including pyrimethamine, trimethoprim, trimetrexate-glycuronate, and piritrexim, a strong inhibition of Toxoplasma growth was observed, which was associated with striking morphological changes of the parasites. The 50% inhibitory concentrations were 0.04 microgram/ml for pyrimethamine, 2.3 micrograms/ml for trimethoprim, 0.16 ng/ml for trimetrexate-glycuronate, and 6.9 ng/ml for piritrexim. When sulfonamides and dihydrofolate reductase inhibitors were used in combination, a synergistic effect was observed with sulfadiazine combined with pyrimethamine, trimetrexate-glycuronate, and piritrexim; sulfisoxazole combined with pyrimethamine; and trimethoprim combined with sulfamethoxazole. These results were analyzed in comparison with human pharmacokinetics data.

Animals↗

[Passive smoking and respiratory diseases. Current data].

Smoking is now unanimously recognised as a pathological factor and a major carcinogen. It is estimated that it is responsible for around 10% of the overall mortality in France or more than 50,000 deaths per year and in the United States for around 15% of the overall mortality or 300,000 deaths per year. There has been recent evidence that the risk linked to the inhalation of tobacco smoke does not appear only in active smokers, but also in all subjects who are involuntarily exposed to tobacco smoke. We have here planned a general review of the epidemiological studies which have looked for an association between passive exposure to tobacco and respiratory disease. In children, an increase in symptoms and respiratory infections has been observed, as well as a slowing down in pulmonary growth. In adults the effect of involuntary exposure to tobacco smoke seems above all to be carcinogenic. It is estimated that there is a 25% increase in the risk of bronchial cancer in a non smoker married to a smoker when compared to the risk observed in a non exposed non smoker. Thus the disastrous effect of smoking appears without any threshold.

Adult↗

[Prognosis of surgically treated colorectal neoplasms. Contribution of multivariate analysis].

Dukes' classification is the most usually used method of staging in colorectal carcinoma. However the pitfalls of this classification may be attested by the multitude of modifications of Dukes' staging during the last sixty years. The aim of our study was to evaluate the influence of 25 variables on survival in colorectal carcinoma using the Cox model. This study was performed in 321 patients operated on for colorectal carcinoma. In the 252 patients who had had a curative resection univariate analysis showed that survival was related to 6 variables: age, juxtatumoral lymph node involvement, an abdominal mass, complicated carcinoma, duration of symptoms, and depth of tumor penetration. Stepwise analysis showed the independent influence of 7 variables on survival: age, lymph node involvement, depth of tumor penetration, duration of symptoms, direct spread, preexisting deficiencies, and sex. A byproduct of the regression coefficient of Cox' model was a numerical value for each of these predictive factors. A single composite score was obtained by adding the individual scores of factors from which a prediction of outcome can be made. Applying this model to each of the 252 patients resected for cure, we established three prognostic groups. They predict survival more accurately than the Dukes' system. Our scoring system based on multivariate analysis must successfully defined prognostic groups of patients in other series. Then, it should be recommended for staging in curative resection for colorectal carcinoma.

Aged↗

A quantitative study of the bias in estimating the treatment effect caused by omitting a balanced covariate in survival models.

This paper discusses the quantitative aspects of bias in estimates of treatment effect in survival models when there is failure to adjust on balanced prognostic variables. A simple numerical example of this bias is given along with approximate formulae for its calculation in the multiplicative exponential survival model. The accuracy of the formulae is checked by simulation. In addition, approximate calculations and simulations of power loss and the effects of omitting more than one prognostic covariate are presented. The Weibull and Cox models are also examined using simulation. Study of this bias is pertinent to much applied work, and shows that the effect of omitting balanced covariates can be modest unless the variables are strongly prognostic or many in number. This work emphasizes the need for thorough comparisons of adjusted and unadjusted analyses for sensible interpretation of treatment effects.

Humans↗

Prospective assessment of a protocol for selective ordering of preoperative chest x-rays.

Routine preoperative chest x-rays are still widely employed worldwide, although results of many studies do not support their broad utilization. A protocol for selective ordering of preoperative chest x-rays, according to the patient's clinical status, medical history and scheduled surgery, was developed and implemented in a teaching hospital in Paris. The utilization of the protocol during a one-year period was evaluated. Eleven hundred and one chest x-rays were ordered in 3866 patients (28 per cent). Five hundred and sixty-eight x-rays (52 per cent) were abnormal. One hundred and sixty-six (15 per cent) were considered useful by the anaesthetists, who took into account the entire hospital course, although only 51 (5 per cent) had an impact on the surgical plan or anaesthetic management. Among the 2765 patients who did not have a preoperative chest x-ray, two patients could have benefited from the chest x-ray, in the view of anaesthetists. Chart review for these two patients and for patients who had perioperative complications in the absence of a preoperative chest x-ray revealed that no complications could be linked to the lack of preoperative chest x-ray ordering. This study shows that the abandonment of routine ordering of preoperative chest x-rays does not produce adverse effects on patient care.

Adult↗

Usefulness of selectively ordered preoperative tests.

The authors prospectively evaluated the usefulness of 12 preoperative tests (including blood type and screen) ordered selectively according to clinical status and importance of scheduled surgery. Two methods of assessing usefulness of tests were used, taking into account not simply their abnormality yield, but also their impact on patient care during the entire hospitalization: first, usefulness was assessed by anesthetists involved in care; second, usefulness was assessed by an automated analysis of specific clinical situations in which tests were a priori considered useful. In 3,866 patients 15,920 tests were performed; 30% of performed tests were abnormal. As a consequence of test results, surgery was delayed or cancelled in 19 patients and modified in 1, and a treatment was instituted or anesthetic management influenced in 347 (9%). Blood component therapy was instituted in 652 patients (17%). Anesthetists and automated analysis found at least one preoperative test useful in 931 patients (24%) and 890 patients (23%), respectively, whereas on a per-test basis 17% and 9% of tests were found useful. The discrepancy in usefulness assessment was mainly due to differences in evaluation of the usefulness of normal results. This study shows that the usefulness of selectively ordered preoperative tests may be high, but better criteria for their indications are needed, because tests other than those recommended by protocol were found useful.

Adult↗

Phenotypic heterogeneity of B- and T-cell differentiation antigens in B-CLL.

Peripheral blood from 38 B-CLL patients was studied by flow cytometry with 25 clustered or non-clustered monoclonal antibodies (moAbs) in order to characterize the cell surface phenotype of lymphoid cells. All moAbs chosen detected B or CD1-8 T-cell differentiation antigens or MHC class II antigens. The results showed a heterogeneity in the leukemic cell reactivity with the various moAbs and between patients. The restricted B-cell antigens recognized by BL14, Y2955 and anti-class II moAbs were constantly expressed in leukemic cells, while B-cell antigens reacting with FMC7 and BL13 moAbs were variably detected. In addition to CD5 antigens, other T-cell markers, including several epitopes of the CD1 group, were also found to be present on the leukemic cell surface in several cases. The relationship between the various clinical and/or biological features of the disease and the cell surface phenotype was studied. Our results indicated a correlation between the lymphoid cell reactivity with M241 (CD1) and BL13 (CD21) and the severity of the disease.

Antibodies, Monoclonal↗

Enzyme immunoassay to assess effect of antimicrobial agents on Toxoplasma gondii in tissue culture.

Toxoplasma gondii grown on MRC5 fibroblasts in 96-well tissue culture plates was tested for susceptibility to five antimicrobial agents. T. gondii growth was quantitated by an enzyme-linked immunosorbent assay, which was performed directly on the fixed cultures, using a rabbit anti-T. gondii immunoglobulin G as the first antibody and a phosphatase-labeled anti-rabbit immunoglobulin G as the second antibody. Optical density values were highly correlated with the number of T. gondii organisms in the Giemsa-stained cultures (r = 0.89), and an enzyme-linked immunosorbent assay was used to assess the effect of antimicrobial agents at various concentrations. For each drug, regression models were used to quantify the relationship between optical density values and antimicrobial agent concentrations in the cultures. A significant inhibitory effect was found with pyrimethamine and sulfadoxine for concentrations greater than or equal to 0.05 and 30 micrograms/ml, respectively. With spiramycin, a progressive increase in inhibition of T. gondii was observed for increasing concentrations from 1 to 100 micrograms/ml. Ornidyl (difluoromethylornithine) and (2R,5R)-6-heptyne-2,5-diamine, which are ornithine decarboxylase inhibitors, were found to have a marked inhibitory effect for concentrations greater than or equal to 25 and 2 mM, respectively. This proposed method was sensitive and easy to perform and does not require the use of radiolabeled compounds; since it allows experimental design on replicate cultures and can be partially automated, it thus may prove useful for the systematic screening of the activity of new compounds against T. gondii.

Animals↗

Low doses v conventional doses of corticoids in immune thrombocytopenic purpura (ITP): results of a randomized clinical trial in 160 children, 223 adults.

A randomized clinical trial was performed in 160 children and 223 adults with acute immune thrombocytopenic purpura (ITP). The role of corticoids at this phase of the disease is still controversial. Therefore, patients were randomized to receive either conventional doses (1 mg/kg/day) of corticotherapy or low doses (0.25 mg/kg/day) for 3 weeks. The remission, defined by platelet count superior to 100,000/microliter was studied for adults and children after 6 months and 12 months, respectively. The statistical analysis showed no significant difference between the two corticotherapy regimens neither in children nor in adults. Overall, 74% of children and 41% of adults were in remission. For the first time in acute ITP, a randomized prospective trial showed that both in children and adults low dose corticotherapy (0.25 mg/kg/day) proves to have the same efficacy as conventional doses (1 mg/kg/day).

Acute Disease↗

[In vitro measurement of the inhibitory effect of macrolides, lincosamides and synergestines on the growth of Toxoplasma gondii].

The in vitro inhibitory effect of macrolides, synergestines and lincosamides on Toxoplasma gondii was evaluated using an enzyme immunoassay performed directly on the infected cultures. Antimicrobial agents were tested at various concentrations, and regression models were used to quantify the relationship between optical density values (correlated to Toxoplasma count in the cultures) and drug concentrations in the cultures. A significant inhibitory effect was observed with the macrolides (erythromycin, roxithromycin, midecamycin, spiramycin, josamycin and oleandomycin) for concentration of 0.1 to 4 micrograms/ml. This effect progressively increased with increasing concentration of drug in the cultures and reached its maximum value for concentrations of 40 to 250 micrograms/ml. Similarly, clindamycin was found to have a significant inhibitory effect for concentration ranging from 0.5 ng/ml to 100 micrograms/ml. Only a partial inhibitory effect was noted with virginiamycin, pristinamycin and lincomycin. The concentrations giving a 50% inhibition of Toxoplasma growth in the culture were determined from regression models and ranged between 0.15 and 12 micrograms/ml according to the drug. This results confirm that macrolides, lincosamides are effective against Toxoplasma gondii in vitro, and can be proposed for treatment of toxoplasmosis because of their large diffusion, their good tolerance and their concentration in tissues such as lung and placenta.

Animals↗

Is bone marrow biopsy a prognostic parameter in B-CLL?

Four hundred and ninety-three bone marrow biopsies from CLL patients were analysed on the basis of non diffuse versus diffuse bone marrow lymphocytic infiltration patterns. In each clinical stage A, B, and C there were non significant differences in survival rates according to the bone marrow pattern. However in stage A studying the evolution to stage B or C, a significant difference between patients with non diffuse and diffuse pattern was observed.

Biopsy↗

Age as the main prognostic factor in adult aggressive non-Hodgkin's lymphoma.

From 1975 to 1983, 73 patients with aggressive non-Hodgkin's lymphoma were treated with a first-generation program including Adriamycin, VM 26, cyclophosphamide, and prednisone. Thirty-nine patients were under 60 years of age, and 34 were 60 years or older. The clinical and histologic characteristics of the two groups were similar. Using either univariate or multivariate analysis, age appeared as the only prognostic factor. Patients under 60 had a median survival of 48 months, with a five-year survival rate of 47 percent and a five-year disease-free survival rate for complete-remission patients of 72 percent. Patients 60 years or older had a median survival of 18 months with a five-year survival rate of 18 percent and a five-year disease-free survival rate for complete-remission patients of 24 percent. These highly significant differences were related to a non-significantly decreased complete-remission rate and a significantly higher relapse rate in elderly patients. Since patient selection according to age could play a role in the results achieved with intensive chemotherapy programs, randomized trials comparing the various chemotherapy programs for aggressive non-Hodgkin's lymphoma are warranted.

Adolescent↗