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Biomedical subjects

I L Smith

Publications and source records attributed to I L Smith.

At least 55 records · Page 3Linked to original sources
PubMed1984

Effect of protein binding on cefmenoxime steady-state kinetics in critical patients.

The effect of protein binding on cefmenoxime steady-state kinetics was studied in 20 critical patients with gram-negative pneumonia. Sixteen patients were given 1 gm cefmenoxime every 6 hr, two received 2 gm every 6 hr, and two received 2 gm every 8 hr. Serum protein binding was measured by equilibrium dialysis. Assays were by HPLC. Serum cefmenoxime concentration-time data were characterized by a model-independent method based on statistical moment theory. Despite varying renal function in patients, mean cefmenoxime serum concentration-time curves for all three dosing regimens were closely aligned, reflecting successful empiric dosage adjustment. Terminal phase t 1/2 ranged from 0.8 to 2.9 hr and was significantly related to creatinine clearance. Cefmenoxime total clearance was significantly related to both lambda z (2.303 times the slope of the terminal portion of the log-concentration-time curve) and creatinine clearance (CCr). Plasma clearance of free cefmenoxime was more strongly correlated with CCr than the clearance of total cefmenoxime. Drug recovery from 24-hr urine collections at steady state was 76.9 +/- 19.8% of the daily dose (mean +/- SD, n = 13). Cefmenoxime protein binding in patients differed markedly from normal values. A regression equation derived from data on 11 cephalosporins appeared to predict total volume of distribution in the steady state (Vdss-Total) from the fraction of unbound drug accurately. Since cefmenoxime has a high therapeutic index, no clinical consequences are expected to result from variation in protein binding. Observed differences in protein binding between patients and normal subjects could have clinical consequences for highly bound acidic drugs that, unlike cefmenoxime, have narrow therapeutic indices.

Aged↗
PubMed1984

Cimetidine kinetics during resuscitation from burn shock.

Severely burned patients suffer from rapidly changing metabolic and hemodynamic abnormalities that could alter drug kinetics. The kinetics of cimetidine, commonly used in the prophylaxis of acute stress erosions, were studied during fluid resuscitation of 11 patients with mean burn sizes of 45% total body surface area. Six patients were studied after the completion of fluid resuscitation. Total clearance, steady-state volume of distribution, and cimetidine t1/2 did not change between the early period after burn and after fluid resuscitation, but before the completion of fluid resuscitation patients had lower renal and greater nonrenal cimetidine clearance than after resuscitation. The increase in nonrenal cimetidine clearance resulted in decreased urinary recovery of unchanged drug, 50.7 +/- 14% during fluid resuscitation and 81.0% +/- 6% after resuscitation.

Adult↗
PubMed1984

Ranitidine disposition and systemic availability in hepatic cirrhosis.

Single-dose ranitidine kinetics were studied in 10 patients with cirrhosis as proved by liver biopsy. All were clinically stable. After an overnight fast, ranitidine was given in a randomized crossover order as a bolus intravenous injection (50 mg) or was taken by mouth (150 mg). Terminal t1/2 was 2.7 +/- 0.4 hr after oral dosing and 2.9 +/- 0.4 hr after intravenous injection. Total plasma clearance was 470 +/- 170 ml/min and the steady-state volume of distribution was 1.2 +/- 0.2 l/kg. There was considerable intersubject variability in the ranitidine serum concentration-time profile after oral dosing. Systemic availability as assessed by AUC analysis was 58% +/- 11%. Not all of the dose could be recovered in the urine as unchanged ranitidine and its known metabolites after intravenous injection. At 0.5 microgram/ml the serum protein binding of ranitidine was 4.6% +/- 1.3%. It is concluded that disposition of ranitidine in these 10 stable subjects with cirrhosis was not significantly altered. The minor changes observed in some were as likely to be the result of secondary perturbations in physiologic status as to effects of cirrhosis on drug metabolism.

Administration, Oral↗
PubMed1983

Prostanoids in platelet-vascular interactions.

Prostacyclin, the labile prostanoid product of arachidonic acid metabolism in vascular endothelium, is the most potent known inhibitor of platelet aggregation and is highly effective in relaxing vascular smooth muscle. Its production is probably critically important in the maintenance of an intact vasculature. Although there is some evidence that prostacyclin circulates as a hormone, it is probably most important as a locally active agent in preventing thrombosis and maintaining patent vessels. Several factors can influence prostacyclin production, the most important of which probably act locally at sites of vessel wall injury. The most promising therapeutic approaches toward using prostacyclin's beneficial effects in vascular disease may lie in the use of drugs aimed at increasing prostacyclin production. Among these are thromboxane synthesis inhibitors, which act by diverting prostaglandin endoperoxides through the prostacyclin synthetase pathway, and lipoxygenase inhibitors, which might act chiefly by preventing formation of metabolites capable of inhibiting prostacyclin synthetase.

Blood Platelets↗
PubMed1983

Steady-state moxalactam pharmacokinetics in patients: noncompartmental versus two-compartmental analysis.

Moxalactam pharmacokinetics at steady state was examined in a group of 40 patients with presumed or proven abdominal sepsis. Mean steady-state serum concentrations ranged from 27.0 to 211.0 mcg/ml and correlated inversely with creatinine clearance (r = 0.91, p less than 0.0001). Terminal half-life ranged from 1.27 to 8.27 hr and reflected the varying renal function of the patients. Moxalactam total body clearance (CL) displayed excellent correlation with creatinine clearance as 92% (r2 x 100) of the variance in clearance could be accounted for by renal function (p less than 0.0001). Pharmacokinetic parameters were estimated using noncompartmental analysis based on statistical moment theory. Noncompartmentally determined CL was in agreement with CL determined by nonlinear least squares regression (r = 0.99, p less than 0.0001). Moxalactam total body clearance is best predicted from creatinine clearance corrected for body surface area.

Biological Assay↗
PubMed1982

Platelet thromboxane synthesis and release reactions in myeloproliferative disorders.

A group of patients with myeloproliferative disorders was studies with respect to platelet aggregation responses, release of beta-thromboglobulin and incorporated 5-hydroxy-tryptamine, and synthesis of thromboxane b 2. In all patients the resting plasma beta-thrombo-globulin was elevated. Aggregation responses were frequently impaired to adrenaline, arachidonic acid, A23187 and the prostaglandin endoperoxide analogue, U44069. Both 5-hydroxy-tryptamine and beta-thromboglobulin release were greater with patients' platelets than with those of controls in response to adrenaline, ADP and U44069. The patients' platelets produced more thromboxane B2 than did controls, irrespective of the agonist used, yet those aggregating agents which are thought to act by generating thromboxane A2 were relatively ineffective in causing aggregation. This might reflect resistance to thromboxane A2 action in these patients, which is met by increased thromboxane formation.

Adenosine Diphosphate↗
PubMed1981

Purification of the high-Km aldehyde reductase from rat brain and liver and from ox brain.

A procedure is described that yields an apparently homogeneous preparation of the high-Km aldehyde reductase from rat brain. This procedure is also applicable to the purification of this enzyme from rat liver and ox brain. In the latter case, however, the purified preparation could be resolved into two protein bands, both of which had enzyme activity, by polyacrylamide-gel electrophoresis. Since a sample of the ox brain enzyme from an earlier step in the purification procedure only showed the presence of a single band of activity after electrophoresis, this apparent multiplicity probably results from modification of the enzyme, possibly by oxidation, during the final step of the purification. A number of properties of the rat brain enzyme were determined and these were compared with those of the enzyme from rat liver. The two preparations were similar in their stabilities, behaviour during purification, kinetic properties, electrophoretic mobilities and amino acid compositions. Antibodies to the rat liver enzyme cross-reacted with that from brain and the inhibition of both these preparations by the antiserum was similar, further supporting the view that the enzymes from these two sources were closely similar if not identical.

Alcohol Oxidoreductases↗
PubMed1980

The effect of platelets on the in vitro response to prothrombin complex concentrates in F.VIII inhibitor plasma.

Incubation of prothrombin complex concentrates, both non-activated and activated, in plasma enhances coagulation. The effect is reduced with time and is augmented when platelets are present. Such concentrates correct the coagulation abnormality in vitro in haemophilic plasmas with factor VIII inhibitors and the correction is greater in platelet rich than platelet poor plasma. Platelets appear to protect incubated concentrates from inhibitors present in plasma. Platelets may play a role in mediating the in vivo clot-promoting activity of some components of these concentrates. This effect may contribute to unwanted thrombosis or, conversely, may facilitate the sometimes-observed haemostatic effect of concentrates in patients with inhibitors of factor VIII.

Blood Coagulation↗
PubMed1980

Dimensions underlying a hierarchically based assessment of social problem-solving.

The dimensions underlying a procedure designed to assess nine levels of social problem-solving among EMR learners were explored in relation to IQ and MA. Principal-factor solutions followed by oblimin rotations were performed on data collected from 120 EMR children (ages 9 to 14). Results yielded three hierarchical factors, two that were moderately related to IQ and MA and one that was independent of IQ and MA. Explanation of the findings was based on a consideration of the differences between divergent and convergent production abilities.

Factor Analysis, Statistical↗
PubMed1979

Hierarchical assessment of social competence.

Three properties associated with the Test of the Hierarchy of INductive Knowledge (THINK) were examined, namely, that the processes assessed by the measure are (a) cumulative and hierarchical, (b) developmental, and (c) related to behavioral criteria. Analyses of data collected from 120 EMR children between the ages of 9 and 14 years generally support the developmental and criterion-related features of the measure, but only partially confirm the hierarchical component. Discussion of the results was focused on the emphasis necessary in subsequent empirical work and the measure's potential for instructional applications in relation to current assessment issues in special education.

Adolescent↗