Search

1. A method is described for the measurement of phenobarbitone (PB) by reversed phase high performance liquid chromatography (h.p.l.c.) from small samples of whole blood dried onto filter paper strips. 2. The disposition of PB given prophylactically to young children with severe malaria on parenteral quinine is contrasted with that in aparasitaemic Kenyan children on no antimalarial drugs. There were no differences in the disposition of PB between the two groups. 3. Peak blood PB concentrations were equal to or greater than 15 mg l-1 in 27% of the patients on quinine and 23% of those not on quinine; a concentration of 10 mg l-1 was achieved or exceeded by 100% and 92% of each group, respectively, and was maintained for 39 +/- 24 h (mean +/- s.d.), and 33 +/- 21 h, respectively. 4. In an open, dose-finding study, the progress of young children with cerebral malaria given prophylactic PB (10 mg kg-1), was contrasted with that of controls given no seizure prophylaxis. 5. The drug had no apparent effect on depth or duration of coma, but neither was the incidence of seizures reduced. 6. A controlled trial of prophylactic PB in young children with cerebral malaria is needed, but a larger dose than 10 mg kg-1 should be studied. [ABSTRACT FROM AUTHOR]

Investigates the relationship between T- and B-cell reactivity to the recombinant 16 kilo Dalton alpha-crystallin antigen of Mycobacterium tuberculosis. Role of antigen in the ability of M. tuberculosis to survive in a state of nonreplicating persistence within the host's intracellular environment; Negative correlation between antibody production and cell proliferation.

Activation of lymphocytes leads to the modulation of a number of surface molecules. We have investigated the expression of one such molecule, L-selectin, following activation of γδ T cells with Mycobacterium tuberculosis. L-selectin is modulated during lymphocyte entry into lymph nodes: this modulation reflects the recirculation and homing potential of lymphocytes. We find that stimulation of γδ T cells by M. tuberculosis antigens results in shedding of L-selectin from γδ T cells. Re-expression of L-selectin occurs on removal of antigen suggesting that the regulation of expression is controlled by the presence or absence of antigen. The γδ T-cell receptor (TCR)- positive, L-selectin negative population of peripheral blood lymphocytes appears to be resting cells, as assessed by forward- and light-scatter analysis. We farther find that γδ T cells isolated from a site of infection, the pleural fluid of a tuberculosis patient, are L-selectin negative, and that L-selectin is re-expressed following culture of the pleural fluid γδ T cells in the absence of antigen. These results demonstrate that, in addition to stimulation with polyclonal mitogens, antigen stimulation can also promote the surface shedding of L-selectin and that γδ T cells have the potential to home to sites of infection supporting their role in the immunological defence against infectious micro-organisms. [ABSTRACT FROM AUTHOR]

proliferation and cytokine production profiles by blood mononuclear cells in response to in vitro stimulation with mycobacterial antigens were compared in patients with active tuberculosis and in sensitized healthy controls. Interleukin-4 (IL-4) and interferon-7 (IFN-γ) were detected at single-cell level using the ELISPOT assay. Patients showed significantly (P < 0.01) increased numbers of IL-4 secreting cells and decreased thymidine incorporation, but no significant difference in IFN-γproducing cells in response to the 38,000 MW or 19,000 MW antigens and their immunodominant peptide epitopes. Pronounced individual variations were found in both patient and control groups, when comparing the responsiveness to the mycobacterial extract, two protein antigens and five synthetic peptides. None of the antigens or peptides tested showed preferential stimulation of either IL-4- or IFN-γ-secreting T cells, and proliferation was not correlated with either IL-4 or IFN-γ production. In particular, cytokine responsiveness was of similar frequency in subjects who did or did not show positive proliferation, indicating that the latter test was not fully representative of the active T-cell repertoire. It is concluded that the demonstrated Th2 type of profile in response to two prominent mycobacterial antigens may play a role in the mechanisms of defective host resistance in tuberculosis. [ABSTRACT FROM AUTHOR]