Documentation: communicating professionalism.
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Biomedical subjects
Publications and source records attributed to G Newell.
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High protein diets acutely elevate the glomerular filtration rate. To characterize this response we administered 1 g of protein/kg body weight as a beef steak meal to nine, healthy male subjects and measured glomerular filtration rate (inulin clearance), renal plasma flow (p-amino hippurate clearance), plasma renin activity, aldosterone and plasma and urinary catecholamines. The subjects ingested the meal on three separate days and were pretreated with either placebo, 50 mg indomethacin (to inhibit renal prostaglandin synthesis), or 10 mg enalapril (to inhibit angiotensin II synthesis). Following placebo treatment protein feeding significantly increased the glomerular filtration rate, from a pre-meal level of 101 +/- 7 ml/min/1.73 m2 to a post-meal level of 130 +/- 6 ml/min/1.73 m2, P less than 0.005. A parallel rise in renal plasma flow and a fall in renal vascular resistance were noted. Indomethacin pretreatment attenuated the increase in glomerular filtration rate following the protein meal, 105 +/- 6 ml/min/1.73 m2 pre-meal level to 118 +/- 4 ml/min/1.73 m2 post-meal, P greater than 0.1. Enalapril pretreatment had no significant effect on protein-induced glomerular hyperfiltration. Protein feeding following placebo increased plasma aldosterone concentration while the concentrations were unchanged in the studies where enalapril or indomethacin was administered. Protein feeding following placebo or indomethacin did not alter plasma renin activity while plasma renin activity rose following enalapril administration. Urinary norepinephrine excretion rose while plasma norepinephrine concentration was unchanged in all three study groups. A decrease in urinary dopamine excretion was also noted four hours after the protein meal was ingested.(ABSTRACT TRUNCATED AT 250 WORDS)
In search of potential therapeutic agents for the acquired immunodeficiency syndrome (AIDS) among homosexual males, we studied in vitro the immunorestorative effect of azimexon in patients with this syndrome. Since a reduction in the ratio between helper inductor and suppressor/cytotoxic T-cell subsets (OKT-4/OKT-8) seems to be the hallmark of the syndrome, we measured azimexon-induced numerical changes in T-cell subsets and correlated them with changes in a simultaneously tested T-cell function as measured by the xenogeneic local graft-versus-host reaction (GVHR). Following incubation of peripheral blood mononuclear cells from 10 homosexual subjects with 10 micrograms/ml of azimexon at 37 degrees C for 1 h, the median number of T cells defined by the OKT-8 phenotype declined from 0.6 X 10(3) to 0.33 X 10(3)/mm3 (p less than 0.02), resulting in an increase in the OKT-4/OKT-8 ratio from 0.65 to 1.37 (p less than 0.01). There were no numerical changes in T cells defined by OKT-3 and OKT-4 phenotypes. Similar decreases in OKT-8-defined T cell occurred among eight heterosexual controls. The restoration of the OKT-4/OKT-8 ratio among the homosexual subjects was associated with a significant improvement in their T-cell function. Thus, the median volume of the local GVHR increased from 38.2 to 63.5 mm3 (p less than 0.02). Parallel changes in OKT-4/OKT-8 ratio and changes in local GVHR following incubation with azimexon were observed. These results suggest that azimexon may be an important immunorestorative agent. Clinical trials with this agent in patients with AIDS or its preclinical complex of symptoms seem warranted.
Thymosin fraction 5 (Thymosin) has numerous immunoregulatory activities including modulation of enzymes involved in lymphocyte maturation. The effect of Thymosin on the purine metabolic enzymes adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and 5' nucleotidase (5'NT) in null and T-enriched peripheral blood lymphocytes from sexually active asymptomatic homosexual males (AS), patients with the AIDS-related symptom complex (ARC), and those with acquired immune deficiency syndrome (AIDS) was examined and compared to its effect on lymphocytes from healthy heterosexual controls. Mean ADA activity was significantly higher in null cells from fourteen AIDS patients than in five asymptomatic homosexuals, ten ARC patients, or 27 controls. Mean PNP activity was significantly elevated in null-enriched lymphocytes from ten ARC and fourteen AIDS patients compared to controls. No differences in these enzymes were found in T-enriched cells from any group. 5'NT was markedly decreased in both null and T lymphocytes in all homosexual groups relative to controls. Homosexuals had significantly elevated percentages of OKT10 positive and Ia positive lymphocytes compared to controls. Thymosin at an optimal concentration of 150 micrograms/ml caused significant decreases in mean ADA and PNP activity in null lymphocytes from ARC + AIDS patients along with a significant decrease in the percentage of OKT10 positive lymphocytes. No phenotypic changes were seen in AS or control lymphocytes. The data suggest that Thymosin has a maturational effect in vitro on immature T cells from symptomatic homosexuals.
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Since decompression from depth is known to produce a fall in platelet count, the effect of altitude decompression and high-altitude exposure on platelets was investigated. Sixteen subjects decompressed without hypoxia to 20,000 ft simulated altitude for two hours showed a significant (P less than 0.01) drop in circulating platelet count of approximately 10% for three days following decompression. Four of five subjects similarly exposed had a shortened autologous platelet survival compared to that prior to exposure. Subjects exposed to 9,800 ft and then 17,600 ft in a mountain environment showed a significant mean decrease in platelet count on day 2 of 7% and 25% respectively, which had returned to control by day 5. Nonhypoxic and hypoxic decompressed rabbits which received homologous chromium-51-labeled platelets had an increase in lung radioactivity compared with sea-level controls. It is postulated that altitude decompression produces platelet reductions similar to these seen after decompression from depth, and that platelets sequester in the pulmonary vascular bed.
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