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H Lecoeur

Publications and source records attributed to H Lecoeur.

47 records · Page 3Linked to original sources

[Prevention of resistance to rifampicin by pyrazinamide in experimental tuberculosis in the mouse].

The capacity of Pyrazinamide (PZA) to prevent the selection of Rifampicin (RMP) resistant mutants was tested by the intravenous innoculation of 160 mice with 2 X 10(6) c.f.u. of M. tuberculosis, and two weeks later, the treatment of the mice either with 10 mg/kg/day RMP alone or with RMP + PZA 150 mg/kg/day. After three months of treatment, lungs and spleen were culture positive in respectively 95% and 90% of the mice treated with RMP alone and in 37% and 24% of the mice treated by RMP + PZA (p less than 10(-5). The strains isolated from lungs and spleen were resistant to Rifampicin in respectively 87% and 75% of the mice treated with RMP alone and in none of those treated with RMP + PZA.

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[Activity of rifampicin administered daily and intermittently on experimental tuberculosis in mice].

Intermittent regimens with rifampicin (RMP) for chemotherapy of pulmonary tuberculosis are cheaper and can be usually supervised more easily than daily regimens. They are recommended, specially, in developing countries. The present study is designed to evaluate the reduction of RMP activity as the interval between doses is increased in experimental mouse tuberculosis. The mice are given 10 mg/kg oral doses of RMP once, twice, three times or six times a week. The RMP activity is measured as the decrease of viable counts (cfu) in the spleen of mice. RMP given once a week has no activity neither in combination with isoniazid and streptomycin on a large population of organisms nor alone on a small population. RMP given alone twice a week has an activity slightly better than RMP given once a week. RMP given alone three times a week has a weak but not worthy activity: the mean number of cfu after a three times weekly treatment is significantly lower than the mean number of cfu in control (p less than 0.001) but significantly higher than the mean number of cfu after a six times weekly treatment (p less than 0.001). These experimental results are consistent with the experimental data on the effects of RMP on the RNA polymerase. They are not favourable to the intermittent administration of RMP in the chemotherapy of tuberculosis.

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[Activity of intermittently administered rifampicin and cyclopentyl rifamycin (or DL473) on experimental tuberculosis in the mouse].

The results of recent experiences with experimental tuberculous chemotherapy in the mouse give information on the activity of rifampicin (RMP) administered intermittently and on the activity of Cyclopentyl-Rifampicin (or DL473). The activity of RMP decreases as one spaces the treatment without increasing the dose. These observations are compatible with the known facts concerning the mechanism of action of RMP on RNA polymerase, and are unfavourable as regards the intermittent administration of RMP. Cyclopentyl-Rifampicin, a new derivative of Rifamycine SV, administered once per week, is as active as RMP administered six days per week, both in the initial as well as the continuation phase of treatment.

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[Sterilizing activity of the main drugs on the mouse experimental tuberculosis (author's transl)].

In a first experiment mice infected intravenously with 10(6) Mycobacterium tuberculosis were randomly treated either with isoniazid (INH) + rifampicin (RMP) 25 mg/kg or with INH + RMP + pyrazinamide (PZA) or with INH + RMP + PZA + streptomycin (SM). The decrease of the viable counts (CFU) in the lungs was similar with all three regimens. In a second experiment, mice were treated for six months either with INH + RMP 25 mg/kg or INH + RMP 10 mg/kg. After a follow-up of six months, mice were killed and their lungs and spleen cultivated. Positive cultures were obtained in 7.5 p. cent of the mice treated with the high dose of RMP and 36.5 p. cent in the mice treated with the low dose (p less than 0.05). A third experiment demonstrated that, during the first two months of treatment, adding PZA to INH + RMP 10 mg/kg increased significantly the overall effectiveness of INH + RMP 10 mg/kg combination. A fourth experiment demonstrated that after three initial months of INH + RMP 10 mg/kg, RMP alone was as effective as RMP + INH or RMP + INH + PZA. It may be concluded that RMP and PZA are both active on the intracellular population of Mycobacterium tuberculosis and that RMP is the only drug to act on persisting Mycobacterium tuberculosis in extracellular lesions.

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[Current data on the bacteriology of leprosy].

Microscopic examination and mouse foot-pad inoculation are the main tools in Mycobacterium leprae bacteriology. Microscopic examination enables to calculate bacteriological (IB) and morphological (IM) indexes. The former scores the density of acid-fast organisms in the lesions and the latter scores their viability since only solidly stained acid-fast organisms are likely to be alive. Mouse foot-pad inoculation provides the opportunity for studying the growth curve of M. leprae. Alterations of this growth curve under drug therapy enable to assess the antileprosy activity of drugs and to determine the drug sensitivity of organisms. Acquired and primary drug resistances to DDS are to date the most important events in the chemotherapy of leprosy. Researches are in progress on mice with congenitally reduced immunological capacity (nu/nu mice) and on antileprosy vaccination. Although no decisive advances have been obtained in these fields, researches in progress are promising.

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