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Biomedical subjects

B J Luft

Publications and source records attributed to B J Luft.

At least 91 records · Page 5Linked to original sources
PubMed1988

Treatment of late Lyme borreliosis--randomised comparison of ceftriaxone and penicillin.

23 patients with clinically active late Lyme disease were randomly assigned to intravenous treatment with either penicillin or ceftriaxone. Of the 10 treated with penicillin, 5 were judged treatment failures; of the 13 who received ceftriaxone, only 1 did not respond. An additional 31 patients were subsequently treated with ceftriaxone 4 g/day (n = 17) or 2 g/day (n = 14); success rates in both groups were comparable to those in the cohort randomised to ceftriaxone. Patients unresponsive to ceftriaxone were more likely to have received corticosteroid treatment.

Administration, Oral↗
PubMed1988

New chemotherapeutic approaches in the treatment of Lyme borreliosis.

1. It was demonstrated that while B. burgdorferi may be sensitive to relatively small concentrations of penicillin and ceftriaxone, the organism is killed slowly. This implies that, as in syphilis, prolonged blood levels of these drugs may be necessary in order to ensure cure. In contrast, the activity of tetracycline is more rapid in its action but is more dependent on drug concentration achieved. Unfortunately, the MIC and MBC for some strains are at or above the peak level achieved under optimal conditions. 2. Increasing the concentrations of penicillin or ceftriaxone above the MIC for the organism has little effect on the rate of killing. In contrast, the killing by tetracycline can be augmented by increasing concentrations of the drug. 3. Ceftriaxone is more active than penicillin, as measured by MIC, against the five strains of B. burgdorferi tested. 4. Ceftriaxone was efficacious in the treatment of Lyme borreliosis, which was recalcitrant to penicillin therapy. In a randomized trial comparing ceftriaxone to high-dose penicillin therapy, ceftriaxone was significantly more efficacious than penicillin in the treatment of the late complications of Lyme borreliosis.

Anti-Bacterial Agents↗
PubMed1988

Intrathecal production of antibodies against Toxoplasma gondii in patients with toxoplasmic encephalitis and the acquired immunodeficiency syndrome (AIDS).

We attempted to determine whether patients with the acquired immunodeficiency syndrome (AIDS) and toxoplasmic encephalitis produce Toxoplasma antibodies in the central nervous system, and whether these antibodies would be useful for diagnosing toxoplasmic encephalitis. Thirty-seven patients with AIDS and toxoplasmic encephalitis and 11 patients with AIDS alone were studied. All patients had serum IgG but not IgM Toxoplasma antibodies. Twenty-three of the patients with AIDS and toxoplasmic encephalitis had Toxoplasma antibody in cerebrospinal fluid compared to none of the patients with AIDS alone. Of the patients with AIDS alone who had serum antibodies to T. gondii, none had Toxoplasma antibodies in cerebrospinal fluid. Production of antibodies in the central nervous system was seen in 11 of 16 patients with AIDS and toxoplasmic encephalitis but not in 4 patients in the control group who only had Toxoplasma antibody in their cerebrospinal fluid. These results suggest that production of T. gondii antibodies in the central nervous system may be diagnostic of toxoplasmic encephalitis.

Acquired Immunodeficiency Syndrome↗
PubMed1988

In vitro generation of adherent mononuclear suppressor cells to Toxoplasma antigen.

Adherent mononuclear cells have been found to suppress the lymphocyte proliferation, of T lymphocytes of patients with various chronic infections, to pathogen-specific antigens. To explore mechanisms involved in the generation of these suppressor cells, we established an in vitro method for the generation of suppressor-adherent mononuclear cells. Adherent mononuclear cells separated from mononuclear cells from subjects with serological evidence of chronic Toxoplasma infection could be induced, by preincubation with Toxoplasma antigen for 8 days, to suppress the proliferative response to autologous mononuclear cells to Toxoplasma antigen (TA) (mean suppression = 47%) and tetanus toxoid (TT) (mean suppression = 39%) compared to the proliferative response of autologous mononuclear cells co-cultured with no antigen. When adherent cells were removed after 1-day culture there was no significant suppression of the lympho-proliferative response to TA or TT. Induction of the adherent suppressor cell depended on the presence of CD4-positive T cells and not CD8-positive T cells. Adherent suppressor cells acted directly on the proliferative response of CD4 cells to antigen. The adherent cells contained 90 +/- 5% esterase-positive cells. In cell-mixing experiments, equal numbers of CD8-positive T cells pretreated in a similar manner did not have a suppressive effect. However, pretreated CD4-positive cells did have a suppressive effect at higher concentrations of cells than found in the adherent cells. Indomethacin did not alter the suppressive effect. These studies demonstrate the induction of adherent suppressor cells in vitro and implicate the macrophage and CD4-positive T cells as the suppressor cells.

Animals↗
PubMed1988

Experimental cryptosporidiosis in fetal lambs.

Fetal lambs were infected in utero with purified sporulated oocysts of Cryptosporidium parvum in order to study pathogenesis and host cellular response to the enteropathogen. Ileal loops (IL) of fetuses, 124-130 days of gestation, were inoculated with 1-4 x 10(6) oocysts usually via cannulae in the abdominal wall of the ewe. Oocysts, both free and phagocytosed, were observed in the IL content as early as day 1 post-inoculation (PI). The percentage of oocysts phagocytosed by the host's polymorphonuclear neutrophils (PMN's) and mononuclear cells remained high up to day 13, the last day of examination. Numerous parasites were observed at days 6, 7, and 12 PI in the microvilli of the ileum with hypercellularity of the lamina propria, which consisted of a mixed infiltration of PMN's, mononuclear cells, including lymphoid cells, and a few eosinophils. Cytolysis and extrusion of epithelial cells, often heavily parasitized by various stages of the parasite, as well as inflammatory cells, were prominent in luminal contents. Germinal centers were prominent in mesenteric lymph nodes draining the infected loops by day 12 PI. Depletion of lymphoid cells was already present in Peyer's patches by day 4 PI.

Animals↗
PubMed1987

In vivo and in vitro activity of roxithromycin against Toxoplasma gondii in mice.

Roxithromycin protected mice against a lethal infection with the extremely virulent RH strain and the C56 strain of Toxoplasma gondii. Therapy initiated 2 h after infection with 2 X 10(3) or 2 X 10(4) RH or C56 tachyzoites protected more than 80% of the mice, compared with 0% of untreated controls (p less than 0.001). Paradoxically, Toxoplasma gondii was isolated more frequently (greater than 80%) in treated mice surviving infection with the less virulent strain (C56) than those surviving infection with the more virulent RH strain (less than 25%). Furthermore, in vitro studies revealed that roxithromycin at dosages up to 250 micrograms/ml had no effect on the proliferation of Toxoplasma gondii in murine peritoneal macrophage cultures.

Acute Disease↗
PubMed1987

Characterization of the Cryptosporidium antigens from sporulated oocysts of Cryptosporidium parvum.

The antigenic constituents of sporulated Cryptosporidium parvum oocyst antigens were characterized with antisera from mice immunized against C. parvum. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by silver staining defined the major proteins. Six of seven lectins used recognized as many as 15 bands. The lectins concanavalin A, Dolichos biflorus, and wheat germ agglutinin showed strong activity against the same eight bands with molecular weights ranging from 72,000 to greater than 100,000. An enzyme-linked immunosorbent assay was used to detect antibody to C. parvum. Antibody binding was significantly decreased by heat and enzymatic treatment with trypsin, protease, and mixed glycosidases. C. parvum antigens were further defined by the reactivity of immune sera with a C. parvum sonicate preparation separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrophoretically transferred to nitrocellulose paper. Antisera from orally infected mice consistently recognized four antigens with molecular weights ranging from 72,000 to greater than 100,000. These antigens also bound concanavalin A. Treatment of the antigen preparation with mixed glycosidases reduced the reactivity of antisera with most antigens with molecular weights greater than 60,000. The data suggest that the antigenic composition of C. parvum is complex and that carbohydrates alone or in association with lipids or proteins may be important in the immune response to C. parvum.

Animals↗
PubMed1986

Demonstration of T-cell dysfunction during acute toxoplasma infection.

Mice were infected with the virulent RH and the relatively avirulent C56 strains of Toxoplasma gondii (TG). The concanavalin A (Con A)-stimulated lymphoproliferative response of these animals and interleukin-2 (IL-2) production by their lymphocytes were assessed 3 and 6 days postinfection. The proliferative response of splenocytes (SC) and T-enriched cells from all infected groups was significantly (P less than 0.05-0.005) depressed. Partial removal of macrophages (m phi) or addition of indomethacin had no effect on the depressed proliferative response of SC from mice infected with the RH strain of TG for 6 days (RH6), and only partially improved that from the other infected groups. IL-2 production of T-enriched cells, obtained by scrupulously removing m phi using sequential adherence of SC to plastic and nylon wool, was markedly decreased in all infected mice. These data indicate that both m phi and T cells are involved in the immunodepression in toxoplasmosis. Except for the RH6 group, the depressed lymphoproliferative responses of all infected groups were entirely reconstituted by exogenous IL-2, but their peak response never reached that of the control group. Therefore, the decreased lymphoproliferation could not be explained solely by a defect in IL-2 production. The proliferative response of the RH6 lymphocytes, in the presence of Con A, was significantly lower than without Con A at each IL-2 concentration added. This suggests the presence of an active suppressor factor inducible by Con A. The RH strain of TG caused a greater degree of immunodepression than the C56 strain, suggesting an association between the virulence of different strains of TG with their ability to immunosuppress.

Acute Disease↗
PubMed1986

The effects of cyclosporine on Toxoplasma gondii in vivo and in vitro.

We examined the effect of cyclosporine on Toxoplasma infection in vivo and in vitro. Administration to mice of 150 mg/kg/day cyclosporine variably affected mortality in four separate experiments. IgG (Sabin-Feldman dye test) and IgM enzyme-linked immunosorbent assay antibody titers were significantly depressed in mice treated with cyclosporine. These results suggested the possibility that cyclosporine possesses anti-Toxoplasma activity. Thus, macrophages were incubated with cyclosporine before and after infection with Toxoplasma. Treatment with 0.5, 1, and 5 micrograms cyclosporine/ml during or after challenge of macrophage monolayers with Toxoplasma inhibited replication of Toxoplasma (and resulted in killing of Toxoplasma). The effect of cyclosporine on development of activated macrophages was studied. Cyclosporine administered to mice at a dose of 150 mg/kg/day neither accelerated nor delayed activation of macrophages (assessed by inhibition of Toxoplasma replication in vitro) by i.v. injection of either Corynebacterium parvum or Toxoplasma. Cyclosporine affects mortality variably in murine toxoplasmosis, depresses synthesis of IgG and IgM Toxoplasma antibody in vivo, does not prevent activation of macrophages in vivo, and possesses anti-Toxoplasma activity in vitro and perhaps in vivo. Cyclosporine may be the preferred immunosuppressive agent for recipients of an organ transplant who are at high risk for toxoplasmosis (e.g., seronegative recipients who have received organ from seropositive donors).

Animals↗
PubMed1986

Activity of roxithromycin (RU 28965), a macrolide, against Toxoplasma gondii infection in mice.

Roxithromycin (RU 28965), an ether oxime derivative of erythromycin, protected mice against a lethal infection with the virulent RH strain of Toxoplasma gondii. Therapy begun 24 h before, 2 h after, and 24 h after infection with 2 X 10(3) tachyzoites protected 90, 80, and 50% of the mice, compared with 0% of untreated controls (P less than 0.05 to 0.001). Toxoplasma was isolated in less than 20% of surviving roxithromycin-treated mice.

Animals↗