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Biomedical subjects

D Gilbert

Publications and source records attributed to D Gilbert.

At least 127 records · Page 7Linked to original sources
PubMed1991

Combination therapy with ciprofloxacin plus azlocillin against Pseudomonas aeruginosa: effect of simultaneous versus staggered administration in an in vitro model of infection.

The effect of dose scheduling on the pharmacodynamics of simulated human doses of ciprofloxacin (200 mg intravenously [iv] every 12 h) and azlocillin (4 g iv every 12 h) alone or in combination against Pseudomonas aeruginosa was studied in a two-compartment in vitro kinetic model of infection. Studies with the two drugs in combination were compared using simultaneous or staggered (first doses of each drug were administered 6 h apart) dosing schedules. Bacterial regrowth and resistance were prevented by all combination dosing schedules; however, the simultaneous regimen consistently provided the greatest extent of killing for all strains, particularly in those initially resistant to ciprofloxacin. These enhanced effects of the combination were corroborated by an increase in the peak and duration of bactericidal activity in the analogous "serum" compartment of the model. These data show the potential usefulness of simultaneous dosing of an antipseudomonal beta-lactam with ciprofloxacin against P. aeruginosa.

Azlocillin↗
PubMed1991

The effect of xanthine/xanthine oxidase generated reactive oxygen species on synaptic transmission.

The effect of reactive oxygen species generated by the interaction of xanthine and xanthine oxidase on synaptic transmission was examined at the squid giant synapse and the lobster neuromuscular junction. Exposure of these synaptic regions to xanthine/xanthine oxidase produced a significant depression in evoked release, with no change in either resting membrane properties or in the action potential. Addition of catalase to the xanthine/xanthine oxidase-containing media partially blocked the synaptic depression, indicating that H2O2 contributes to the synaptic changes induced by exposure to xanthine/xanthine oxidase. H2O2 applied directly to the perfusing media also produced a decrease in synaptic efficacy. The results demonstrate that reactive oxygen species, in general, depress evoked synaptic transmission.

Action Potentials↗
PubMed1991

Familial and psychological correlates of smoking in black and white adolescents.

Cigarette smoking is considered to be the single most preventable contributor to chronic diseases, but there is still great controversy about the initiation and maintenance of smoking among adolescents. The goal of this study was to examine familial and psychological factors that contribute to the initiation and maintenance of smoking among black and white adolescents. To accomplish this, we tested 602 male (275 black and 327 white) and 460 female (174 black and 286 white) adolescent students enrolled in health classes in Tampa, Florida. Among blacks, 15.6% were currently smoking cigarettes, compared to 34.8% of the white students. Blacks who initiated smoking were most influenced by having a sister who smoked, while maintenance was most influenced by an older brother who smoked. In contrast, white adolescents who initiated smoking were more likely to have an older brother who smoked, while maintenance of smoking was predicted by having a father who smoked. Furthermore, the data show that both the initiation and the maintenance of smoking among blacks is related to the experience of intense feelings of anger and irritability, while among white adolescents, these emotions contribute only to the initiation of smoking. These data indicate that smokers and nonsmokers differ in their emotional reactions to stress, and that ethnicity (black vs white) is an important determinant in the association between smoking and emotional reactions to stress. The overall pattern of the findings in this inquiry suggests that the efficacy of antismoking treatment procedures could be enhanced by targeting exaggerated emotional reactions for modification. The data also suggest that smoking prevention programs for adolescents should take into consideration pressures to smoke that may arise from having family members who smoke. Given the inherent problems of a cross-sectional research design, future research is needed to clarify the interrelationships between smoking, ethnicity, and measures of the experience and expression of anger.

Adaptation, Psychological↗
PubMed1990

[Lupus erythematosus disseminatus, lesional mechanisms, pathogenesis and genetics].

Systemic lupus erythematosus (SLE) is a model of autoimmune disease. Its study, and that of spontaneous murine models, have benefited from new immunological and molecular biology techniques. New hypotheses have been put forward to explain the mechanisms of SLE lesions. The genetic origin of autoantibodies begins to be better known. Auxiliary CD4+ lymphocytes seem to play a capital role in the occurrence of lymphocyte abnormalities. The disease is multigenic. Much work is currently devoted to the identification and characterization of genetic factors.

Autoantibodies↗
PubMed1990

Enhanced production of superoxide anion by microglia from trisomy 16 mice.

Disruption of normal oxygen radical metabolism in the CNS may contribute to the neuropathological changes associated with Down syndrome (trisomy 21) and its mouse counterpart, the trisomy 16 (Ts16) mouse. One potent source of oxyradicals is the CNS-specific macrophage, the microglial cell. We prepared primary glial cultures from the cerebral cortices of Ts16 and normal littermate mice taken at day 15 of gestation. Microglia were isolated from confluent cultures after 14 days in vitro and assayed for superoxide anion production using a cytochrome C reduction assay. Stimulation by either opsonized zymosan (OPZ) or phorbol myristate acetate (PMA), produced significantly higher levels (2.8-20 fold) of superoxide per mg protein in Ts16 microglial cultures. Resting, i.e. unstimulated secretion, was not significantly different from littermate controls. Astrocyte enriched cultures, stimulated by OPZ, exhibited low levels of superoxide production which was higher in Ts16 mice than normal littermates. Microglial enriched cultures from rat neonatal cerebral cortices were exposed for 24 h to medium from the Ts16 glial cultures. Superoxide production in the Ts16 media treated rat microglia was significantly higher than in those treated with littermate conditioned media.

Animals↗
PubMed1990

Significance of "extravascular" protein binding for antimicrobial pharmacodynamics in an in vitro capillary model of infection.

The effect of protein binding in an "extravascular" space on antimicrobial pharmacodynamics was studied in an in vitro capillary model of infection. Simulated 500-mg oral doses of dicloxacillin (approximately 96% bound) or cephalexin (less than 5% bound) were administered every 6 h for four doses. A 10-fold-higher dose of dicloxacillin was also studied to determine the effect of drug concentration on the reduction of bacterial killing in the presence of protein. Staphylococcus aureus ATCC 25923 was inoculated into peripheral chambers filled with either Mueller-Hinton broth or Mueller-Hinton broth plus 25% human serum. Serial samples for bacterial counts were collected over 24 h. The presence of serum in the chambers significantly reduced bacterial killing by dicloxacillin but not by cephalexin during the first 6 h (two-way analysis of variance, F = 6.04, P less than 0.05) but not at 24 h. Reduction of dicloxacillin activity in serum-containing chambers persisted with the higher dose. These data suggest that despite attaining higher total drug concentrations in protein-containing extravascular spaces with highly bound drugs, protein binding reduces bactericidal activity during the early stages of treatment in this model.

Anti-Infective Agents↗
PubMed1989

The action of hydrogen peroxide on paired pulse and long-term potentiation in the hippocampus.

The action of a reactive oxygen intermediate, that is, hydrogen peroxide (H2O2) on modulation of synaptic transmission was examined in the hippocampal brain slice preparation. Microinjection of H2O2 into the apical dendritic region of the CA1 pyramidal cells produced no change in either the pattern or amplitude of paired pulse facilitation compared to saline injection (control). Long term potentiation (LTP), induced by high frequency stimulation of homosynaptic inputs, however, was blocked by microinjection of H2O2 into the dendritic tree. LTP was seen in only 2 out of 10 slices investigated when treated with H2O2 while LTP was seen in 4 out of 5 slices when saline injected. The results suggest that a reactive oxygen intermediate can selectively modify synaptic mechanisms in the hippocampus.

Action Potentials↗
PubMed1989

The use of adhesives in chondrocyte transplantation surgery: in-vivo studies.

Two commercial adhesive preparations--fibrin glue and mussel adhesive protein (MAP)--were tested in-vivo for their ability to fix a chondrocyte allograft internally. While results for the fibrin, including additional testing for chondro inductive/conductive properties, were at best inconclusive, the results for MAP are highly promising.

Animals↗
PubMed1988

Effect of dose and schedule on cefoperazone pharmacodynamics in an in vitro model of infection in a neutropenic host.

Previous studies have shown that cefoperazone given in frequent, large doses is effective in the treatment of infection in patients with cancer. The pharmacodynamics of 2- and 4-g doses of cefoperazone administered either as a single dose or at 12-hour intervals were studied in an in vitro model that simulates infection in a neutropenic patient. One strain each of Pseudomonas aeruginosa (minimal inhibitory concentration [MIC] = 2 micrograms/ml), Staphylococcus aureus (MIC = 1 microgram/ml), Escherichia coli (MIC = 0.06 micrograms/ml), and Klebsiella pneumoniae (MIC = 0.25 micrograms/ml) was studied. The initial dose reduced the inoculum by approximately 3 logs for the Pseudomonas and the staphylococci and 3 to 5 logs for the other organisms. No significant differences in killing were found between the 2- and 4-g doses. Regrowth of Pseudomonas and staphylococci occurred with the single dose but not with the every-12-hour regimen. These data support the clinical use of cefoperazone in doses every 12 hours.

Agranulocytosis↗
PubMed1988

Two populations of complement factor H differ in their ability to bind to cell surfaces.

Using hydrophobic affinity chromatography on phenyl-Sepharose, human complement factor H can be separated into two subpopulations, phi 1 and phi 2. Although phi 1 and phi 2 are known to differ in their aggregation properties under non-physiological low ionic strength conditions, no difference in aggregation state was detected under the conditions used for cell-binding experiments. We have investigated these two subpopulations further to determine whether functional differences exist between them. The subpopulation phi 2 was found to bind specifically and saturably to the surface of Raji cells. The binding of the other subpopulation, phi 1, was low, and essentially non-specific. A monoclonal anti-factor H antibody, BGH-1, was raised which recognizes preferentially the phi 2 subpopulation and inhibits the binding of factor H to cell surfaces.

Antibodies, Monoclonal↗
PubMed1988

Vancomycin pharmacokinetics, renal handling, and nonrenal clearances in normal human subjects.

The renal handling of vancomycin is unknown. Previously reported studies have not achieved steady-state conditions with constant vancomycin concentrations. We measured systemic vancomycin clearance simultaneously with the renal clearances of vancomycin, creatinine, inulin, and para-aminohippurate in nine healthy subjects at steady-state serum vancomycin concentrations of 7 and 14 mg/L. For all steady-state observations the renal clearance of vancomycin was 89 +/- 11 ml/min (mean +/- SE), the clearance of inulin 105 +/- 9 ml/min, the clearance of creatinine 117 +/- 9 ml/min, and the clearance of para-aminohippuric acid 496 +/- 41 ml/min. The systemic clearance of vancomycin was 131 +/- 7 ml/min. The clearances of creatinine, inulin, and para-aminohippuric acid and the renal clearance of vancomycin were not statistically different at both steady-state vancomycin concentrations. The ratio of the renal clearance of vancomycin to the clearance of inulin was 0.89 +/- 0.06 and to creatinine clearance 0.79 +/- 0.05. Both ratios were independent of vancomycin concentration, urine flow rate, and filtration fraction. The systemic clearance of vancomycin was 10% greater at serum vancomycin concentrations of 14 mg/L than at 7 mg/L (p less than 0.05) because of an increase in the nonrenal clearance. Therefore in healthy subjects, 30% of the systemic vancomycin clearance is by nonrenal mechanisms and this nonrenal clearance is concentration dependent. Assuming protein binding to be between 10% and 20%, renal vancomycin excretion is predominantly by glomerular filtration. Small amounts of tubular vancomycin transport cannot be excluded by these techniques.

Adult↗