In vitro activity of ciprofloxacin, sparfloxacin, ofloxacin, amikacin and rifampicin against Ghanaian isolates of Mycobacterium ulcerans.

MICs of ciprofloxacin, sparfloxacin, ofloxacin, amikacin and rifampicin were determined for 14 primary clinical isolates and three reference isolates of Mycobacterium ulcerans by modifying a standard agar dilution method for testing Mycobacterium tuberculosis sensitivity. All these antimicrobials were active against every isolate of M. ulcerans. Sparfloxacin exhibited the highest activity and ofloxacin was the least effective. Rifampicin exhibited the broadest range of activity.

Lack of peripheral neuropathy in Beagle dogs after 53 weeks oral administration of thalidomide capsules.

Thalidomide (Thalomid) is approved for use in the US to treat complications from leprosy. Peripheral neuropathy is a dose-limiting adverse event in humans. As part of a nonrodent regulatory toxicology study, Beagle dogs were fed orally via encapsulation for 53 weeks. A component of this study was to determine if the dogs developed peripheral neuropathy. Twenty-eight male and 28 female Beagle dogs approximately 8-10 months of age were used. They were dosed at 43, 200 or 1000 mg/kg for 53 weeks followed by a 4-week treatment-free recovery period. Nerve function was assessed by electrophysiological measurements of the tibial nerve prior to dosing and at weeks 13, 27, 38 and 51. Representative dogs from each group were sacrificed at 26, 53 and 58 weeks and histologic and ultrastructural evaluations were performed on the sural nerve. Thalidomide had no effect on sensory nerve conduction velocity, duration or amplitude of the action potential. At 27 weeks, mean sensory nerve action potential amplitude for females at 43 mg/kg was significantly greater than control but was not evident at 39 weeks. Mean duration of sensory nerve action potential seemed to increase with similar magnitude over time in all dose groups including controls. Histological and ultrastructural evaluation of sections of sural nerve did not identify treatment-induced differences between control and thalidomide-dosed animals after 26 and 53 weeks of treatment. Additionally, no differences were observed following a 5-week treatment-free period at week 58. In contrast to humans, Beagle dogs did not develop thalidomide-induced peripheral neuropathy under conditions of the study.

Susceptibility of thymectomized and irradiated mice to challenge with several organisms and the effect of dapsone on infection with Mycobacterium leprae.

B6C3F1 mice that had been thymectomized at 8 to 12 weeks of age, subjected to 950 R of whole-body X irradiation, and transfused with syngeneic bone marrow were challenged in a footpad with Mycobacterium leprae or M. marinum, or intravenously or intraperitioneally with Listeria monocytogenes. Also, mice inoculated with M. leprae in a hind footpad were administered dapsone in the mouse chow. The thymectomized-irradiated (T + R) mice did not survive as well as non-thymectomized mice when housed in the vivarium with no special precautions, but survived sufficiently well to permit the completion of some long-term experiments. M. leprae multiplied to a higher "ceiling" and survived longer in the T + R mice than in the non-thymectomized controls. But a ceiling to multiplication of M. leprae was imposed, and finally the organisms were killed. The histopathological appearance of the footpad tissues, studied by electron microscopy, was consistent with the measurements of bacterial numbers and viability. Swelling of the footpad after local inoculation with M. marinum was greater in T + R mice than in non-thymectomized controls. Similarly, the number of L. monocytogenes following intravenous challenge was greater in the spleens of T + R than of non-thymectomized mice, and the survival of the T + R mice was impaired after intraperitoneal challenge with L.monocytogenes, compared to the survival of non-thymectomized mice. None of these differences was striking, suggesting that these T + R mice had retained or regained some immune competence. The effects of dapsone treatment of T + R mice inoculated with M. leprae were much the same as those of treatment of non-thymectomized mice. Because these T + R mice were not greatly immunosuppressed, they would not have provided a model of human lepromatous leprosy suitable for chemotherapeutic studies.

Early response of mouse foot pads to Mycobacterium laprae.

The purpose of these experiments was to study the early response of mouse foot pads to Mycobacterium leprae. To accomplish this, mice were inoculated in both foot pads with large and small numbers of organisms. The animals were sacrificed at intervals from 2 hr to 27 days after inoculation. The microscopical results, which utilized normal BALB/c and thymectomized-irradiated B6C3F(1) mice, showed that the tissue responded first with an influx of polymorphonuclear cells and later lymphocytes and monocytes. The latter formed a diffuse infiltrate in the tissues. Under conditions where growth normally occurred, the mononuclear cell infiltrate did not persist. The organisms were found within phagocytic cells and the interstitial space. They were always contained within a phagosome and often fused with lysosomes. Most of the organisms appeared to be degenerating at all of the times studied. No organisms were observed in striated muscle fibers of tissues studied.

Ultrastructural changes in cells of the mouse footpad infected with Mycobacterium leprae.

Ultrastructural changes in cells of the mouse footpad are described which occurred during the log phase of multiplication, the plateau, and the stationary phase of growth of Mycobacterium leprae.BALB/c mice were inoculated in the right hind footpad with 5 x 10(3) organisms and sacrificed in pairs at 86 to 173 days after inoculation. Tissue samples were prepared for electron microscopy by standard techniques. During the early growth phase of M. leprae in the mouse footpad, few organisms can be detected. Those present are in macrophages and are bound by a single membrane. The cytoplasm of the macrophage is less dense around the organism. There are few lysosomes, and the bacteria do not appear to be degenerating. At the peak of the growth phase, the organisms within a macrophage are bound by either a single or double membrane. There is an increased number of vacuoles, which are also bound by a double membrane, and lysosomes. During the stationary phase, most of the macrophages have taken on a vacuolar appearance and contain lysosomes. The vacuoles are bound by a double membrane, as are most of the organisms within the macrophage. Many of these organisms appear to be degenerating. Occasionally, organisms are encountered in the sarcoplasm of striated muscle. They are usually bound by a single membrane and do not appear to be degenerating.