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Biomedical subjects

J D Robinson

Publications and source records attributed to J D Robinson.

At least 55 records · Page 3Linked to original sources
PubMed1988

Characteristics of 3-O-methylfluorescein phosphate hydrolysis by the (Na+ + K+)-ATPase.

With 3-O-methylfluorescein phosphate (3-OMFP) as substrate for the phosphatase reaction catalyzed by the (Na+ + K+)-ATPase, a number of properties of that reaction differ from those with the common substrate p-nitrophenyl phosphate (NPP): the Km is 2 orders of magnitude less and the Vmax is two times greater, and dimethyl sulfoxide (Me2SO) inhibits rather than stimulates. In addition, reducing the incubation pH decreases both the Km and Vmax for K+-activated 3-OMFP hydrolysis as well as the K0.5 for K+ activation. However, reducing the incubation pH increases inhibition by Pi and the Vmax for 3-OMFP hydrolysis in the absence of K+. When choline chloride is varied reciprocally with NaCl to maintain the ionic strength constant, NaCl inhibits K+-activated 3-OMFP hydrolysis modestly with 10 mM KCl, but stimulates (in the range 5-30 mM NaCl) with suboptimal (0.35 mM) KCl. In the absence of K+, however, NaCl stimulates increasingly over the range 5-100 mM when the ionic strength is held constant. These observations are interpreted in terms of (a) differential effects of the ligands on enzyme conformations; (b) alternative reaction pathways in the absence of Na+, with a faster, phosphorylating pathway more readily available to 3-OMFP than to NPP; and (c) a (Na+ + K+)-phosphatase pathway, most apparent at suboptimal K+ concentrations, that is also more readily available to 3-OMFP.

Animals↗
PubMed1988

In vitro evaluation of caval filters.

This experiment demonstrated the clottrapping ability of two commercially available filters, the Mobin-Uddin and Greenfield, and three experimental filters developed by Amplatz, Günther, and Gianturco. Each filter was tested in a polyethylene tube simulating the inferior vena cava. Separate series of 10 clots, each 3 cm long and 6 mm or 9.2 mm in diameter, were exposed to the test filter. The Mobin-Uddin and Amplatz filters failed by overload: acutely elevated pressures forced clots outside the skirt of the former, and between the limbs of the latter. The Günther filter trapped all incident clots, but migrated downstream when occluded by clot. The Greenfield filter passed clots at normal pressures between its widely spaced legs. The Gianturco (bird's nest) passed clots at normal pressures as well. While filters performed suboptimally, strengthening the anchoring struts of the Günther filter would result in a secure, effective filter.

Animals↗
PubMed1988

Hyperglycemia is a stress response in acute stroke.

To explore further the relation between admission glucose concentration and outcome in stroke, we measured glucose, fructosamine, and glycosylated hemoglobin concentrations on admission in 216 patients seen within 24 hours after the onset of their first stroke. Fructosamine concentration reflects the degree of glycemia in the preceding 4-6 weeks and glycosylated hemoglobin concentration reflects that in the preceding 3 months. Based on clinical, computed tomographic, and necropsy findings, strokes were classified as cortical infarction, lacunar infarction, or intracerebral hemorrhage. Analyses were done including and excluding 47 diabetic patients. No correlation between neurologic outcome as mortality and fructosamine or glycosylated hemoglobin concentration was found. Survival showed a significant correlation with admission glucose concentration only for patients with intracerebral hemorrhage. Our results suggest that hyperglycemia is unlikely to worsen the outcome of acute stroke and that hyperglycemia probably represents either a latent diabetic state or a stress response.

Acute Disease↗
PubMed1988

Phenytoin dosing in obese patients: two case reports.

Phenytoin is used extensively in the treatment of various forms of epilepsy, and remains the drug of choice in partial and generalized tonic-clonic seizures. Because it demonstrates saturable, Michaelis-Menten pharmacokinetics, dosing of phenytoin within the therapeutic range can be very challenging, especially so in obese patients. We present case reports of two obese patients each requiring very large doses of phenytoin sodium (1000 mg/d) to sustain therapeutic serum concentrations and seizure control. There are very few reports in the literature regarding phenytoin pharmacokinetic changes in the obese. We can only theorize possible changes in these parameters. Further investigation in the form of controlled research trials need to be performed before final dosage recommendations can be given.

Adult↗
PubMed1987

Buffer, pH, and ionic strength effects on the (Na+ + K+)-ATPase.

A dog kidney (Na+ + K+)-ATPase preparation also catalyzes K+-independent and K+-activated phosphatase reactions with p-nitrophenyl phosphate as substrate. K+-independent activity increases with declining pH over the range 7.5 to 5.8, whereas the other two activities decrease. The increased K+-independent activity is similar with imidazole, histidine, and several Good buffers, and is thus attributable to free H+, probably by affecting enzyme conformations rather than by changing affinity for Mg2+ or substrate or by H+ occupying specific K+-sites. The decrease in K+-phosphatase and (Na+ + K+)-ATPase activities with pH also occurs similarly with those buffers, and is not due to changes in apparent affinity for substrate or for cation activators. However, the Good buffers Pipes and ADA inhibit the K+-independent phosphatase reaction strongly, the K+-activated reaction moderately, and the (Na+ + K+)-ATPase reaction little; both contain two acidic groups, unlike the other buffers tested. Inhibition of the phosphatase reaction by Pipes is associated with a decreased apparent affinity for K+ and an increased sensitivity to inhibition by Na+ and ADP, consistent with Pipes hindering conformational transitions to the E2 enzyme forms required for phosphatase hydrolytic activity.

Alkanesulfonates↗
PubMed1987

Effect of new Vacutainer blood collection tubes on plasma lidocaine concentrations.

This study was designed to establish whether plasma lidocaine concentrations changed subsequent to contact with a new formulation of rubber-stopper Vacutainer collection tubes. Plasma lidocaine concentrations from blood samples exposed to rubber stoppers for one hour were compared with concentrations from blood samples which were not exposed to rubber stoppers. Plasma lidocaine concentrations remained essentially unchanged following one-hour exposure to Vacutainer rubber stoppers. The new formulation of "red-top" Vacutainer may be used reliably in lidocaine therapeutic drug monitoring.

Blood Specimen Collection↗
PubMed1987

New heavy-duty exchange guide wire.

A major drawback of currently used exchange guide wires is insufficient stiffness, causing them to buckle or dislodge when used during catheter exchanges. A new heavy-duty exchange guide wire is described that facilitates catheter exchanges around sharp corners, such as those encountered during various cardiac interventional procedures. The wire was successfully used in experimental valvuloplasty and experimental dilation of the ductus arteriosus.

Angiography↗
PubMed1987

Modified sheath introducer for reduced arterial damage.

An introducer-sheath dilator is described, which was modified to protect the leading lip of the sheath during insertion, thus reducing arterial damage. The new sheath and a standard sheath were inserted into the femoral arteries of six dogs. Subsequent histologic examination of the arteries proved the new sheath to be both safe and effective.

Animals↗
PubMed1987

A new torque guide wire.

A new guide wire that provides markedly improved torque control is described. It was compared with a conventional guide wire in two models, one simulating a drainage tube with numerous side holes and one, the biliary tree. The new wire was much more easily controlled than the conventional guide wire and passed through both models significantly faster (P less than .01 and P less than .005). Although some deterioration in control was noted when it was inserted through a catheter in vivo, the new torque-control wire still exhibited a definite improvement over conventional wires in directional control.

Catheterization, Peripheral↗
PubMed1987

Effect of thioridazine on phenytoin serum concentration: a retrospective study.

Serum phenytoin concentrations before and after the addition of thioridazine were retrospectively compared in 27 adults to determine if an interaction occurred between these two drugs. A change in the serum phenytoin concentration of +/- 4 micrograms/ml was considered clinically significant; by this definition four patients (14.8 percent) had an increase, two (7.4 percent) had a decrease, and most (77.8 percent) demonstrated no change. The mean difference was 0.8 microgram/ml +/- 3.7 micrograms/ml and was not found to be statistically significant (p less than 0.1). Clinically important alterations in phenytoin serum concentration as caused by thioridazine appear to be infrequent.

Adolescent↗
PubMed1987

Pharmacokinetic monitoring in the community health-care setting.

Ambulatory care pharmacokinetic profiling has been utilized with increasing frequency over the last decade. The demonstration of need is the first step in initiating outpatient pharmacokinetic service. This article identifies methods used in demonstrating a need and discusses the normal daily activities of an ambulatory pharmacokinetic service located in a university-based family medicine clinic. The reader will also learn of trends that ambulatory care pharmacokinetic programs will become involved with in the near future.

Ambulatory Care↗
PubMed1987

Serum phenobarbital concentration predictions by a personal computer software system.

The ability of a personal computer software system to predict actual serum phenobarbital concentrations (SPC) in outpatients taking phenobarbital chronically was assessed by comparing actual with predicted SPC for accuracy, bias, and precision. Data for a four-year period were collected on patients at an outpatient clinic's pharmacokinetic consultation service. The study group included 50 adults and children with at least one SPC taken at a known time after dose administration. Input variables were weight, sex, height, age, concomitant drugs and diseases, phenobarbital dosage regimen, and the time and reported value of all SPC. Initially, SIMKIN (SIMulated KINetics) simulated dosing regimens on the basis of literature estimates of pharmacokinetic parameters; SPC were then estimated for these regimens and compared with actual values. One or two additional SPC were added to the input data and analyzed, and the predicted SPC compared with actual values. Although SIMKIN's accuracy and bias as measured by regression analysis and mean prediction error, respectively, were within clinically acceptable limits, the precision was not. However, these results are limited by the population studied. Patient compliance, concomitant phenytoin therapy, changes in phenobarbital pharmacokinetic parameters with chronic dosing, and disease interactions may significantly affect predictive ability. The clinical effects of these factors need to be evaluated to further improve predictions.

Adolescent↗
PubMed1987

Pharmacokinetics of loprazolam and its principal metabolite in young subjects and elderly hospital patients.

1. The pharmacokinetics of loprazolam and its principal pharmacologically active metabolite, the piperazine N-oxide, were compared in young subjects (aged 21-25 years) and elderly patients (aged 63-86 years) following single oral evening doses (0.5 mg and 1 mg). 2. Plasma loprazolam was assayed by a specific h.p.l.c./g.c. method. The N-oxide metabolite was assayed by gas chromography. 3. Mean times to peak plasma concentration of loprazolam did not differ significantly between young and elderly subjects and ranged from 1.6-2.7 h. There was, however, a longer mean time to peak concentration of the N-oxide metabolite in the elderly but this was only statistically different after the 0.5 mg dose (4.5 mg young, 6.4 h elderly). 4. Mean peak plasma concentrations of loprazolam did not differ significantly between young and elderly nor did plasma concentrations of the N-oxide metabolite. 5. Although the mean elimination half-life of loprazolam was not statistically significantly different between young and elderly subjects (range 10.9-16.0 h) there was a trend towards somewhat longer half-lives in the elderly. Furthermore, there was a small but significant increase in the half-life of the N-oxide metabolite in the elderly after the 1 mg dose from 11.7 h to 16.7 h. 6. The areas under the plasma concentration time curves for both loprazolam and its N-oxide were greater in the elderly being some 50-68% (mean 132.0 and 111.5 ng/ml h) above those found in young subjects (mean 89.8 and 66.0 ng/ml h).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Reaction sequences for (Na+ + K+)-dependent ATPase hydrolytic activities: new quantitative kinetic models.

To delineate better the reaction sequence of the (Na+ + K+)-ATPase and illuminate properties of the active site, kinetic data were fitted to specific quantitative models. For the (Na+ + K+)-ATPase reaction, double-reciprocal plots of velocity against ATP (in the millimolar range), with a series of fixed KCl concentrations, are nearly parallel, in accord with the ping pong kinetics of ATP binding at the low-affinity sites only after Pi release. However, contrary to requirements of usual formulations, Pi is not a competitor toward ATP. A new steady-state kinetic model accommodates these data quantitatively, requiring that under usual assay conditions most of the enzyme activity follows a sequence in which ATP adds after Pi release, but also requiring a minor alternative pathway with ATP adding after K+ binds but before Pi release. The fit to the data also reveals that Pi binds nearly as rapidly to E2 X K X ATP as to E2 X K, whereas ATP binds quite slowly to E2 X P X K: the site resembles a cul-de-sac with distal ATP and proximal Pi sites. For the K+-nitrophenyl phosphatase reaction also catalyzed by this enzyme, the apparent affinities for both substrate and Pi (as inhibitor) decrease with higher KCl concentrations, and both Pi and TNP-ATP appear to be competitive inhibitors toward substrate with 10 mM KCl but noncompetitive inhibitors with 1 mM KCl. These data are accommodated quantitatively by a steady-state model allowing cyclic hydrolytic activity without obligatory release of K+, and with exclusive binding of substrate vs. either Pi or TNP-ATP. The greater sensitivity of the phosphatase reaction to both Pi and arsenate is attributable to the weaker binding by the occluded-K+ enzyme form occurring in the (Na+ + K+)-ATPase reaction sequence. The steady-state models are consistent with cyclical interconversion of high- and low-affinity substrate sites accompanying E1/E2 transitions, with distortion to low-affinity sites altering not only affinity and route of access but also separating the adenine- and phosphate-binding regions, the latter serving in the E2 conformation as the active site for the phosphatase reaction.

Animals↗