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Biomedical subjects

B E Shapiro

Publications and source records attributed to B E Shapiro.

32 records · Page 2Linked to original sources
PubMed1992

Single-dose pharmacokinetics of piperacillin and tazobactam in patients with renal disease.

Tazobactam is an irreversible inhibitor of many beta-lactamases. In combination with piperacillin, tazobactam exhibits synergy against many beta-lactamase-producing bacteria. The pharmacokinetics of piperacillin and tazobactam were evaluated in eight normal volunteers and in 52 patients with renal dysfunction. Plasma and urine were obtained for up to 30 hours after an infusion of piperacillin and tazobactam (3 and 0.375 gm, respectively). Dialysate samples were collected from patients undergoing dialysis. Piperacillin and tazobactam concentrations were determined by high-performance liquid chromatography. Noncompartmental methods were used for pharmacokinetic analysis. Piperacillin and tazobactam total body clearance, area under the curve, and terminal elimination rate correlated with renal function. Hemodialysis removed 31% and 39% of piperacillin and tazobactam, respectively. During continuous ambulatory peritoneal dialysis, 5.5% of the piperacillin and 10.7% of the tazobactam was recovered in the dialysate over 28 hours. Peak plasma concentrations of both drugs increased minimally with decreasing creatinine clearance. Dosage alterations for creatinine clearance values less than 40 ml/min are recommended.

Adult↗
PubMed1992

Disposition of cefpodoxime proxetil in healthy volunteers and patients with impaired renal function.

The disposition of cefpodoxime in 24 subjects with various degrees of renal function after administration of a single oral dose of 200 mg of cefpodoxime proxetil (equivalent to 200 mg of cefpodoxime activity) was studied. Subjects were assigned to one of four groups (six per group): group I, normal renal function (creatinine clearance [CLCR], greater than ml/min); group II, mild renal impairment (CLCR, 50 to 80 ml/min); group III, moderate renal impairment (CLCR, 30 to 49 ml/min); or group IV, severe renal impairment (CLCR, 5 to 29 ml/min). Although cefpodoxime terminal elimination half-life in group I (2.55 +/- 0.25 h [mean +/- standard deviation]) was not significantly different from that in group II (3.53 +/- 0.74 h), the half-life values for group III (5.90 +/- 1.67 h) and group IV (9.80 +/- 1.21 h) were significantly prolonged compared with those of group I. The mean absorption rate constant was similar among groups and ranged from 0.68 to 0.85 h-1. All groups exhibited absorption lag-times which were comparable (0.30 to 0.41 h), and the apparent volume of distribution was similar among groups. Cefpodoxime apparent total body clearance (CLP/F) values in groups II, III, and IV (132 +/- 29, 112 +/- 41, and 55.7 +/- 9.9 ml/min, respectively) were significantly lower than that in group I (238 +/- 44 ml/min). Cefpodoxime CLP/F was positively correlated with CLCR (r2 = 0.79; P less than 0.05): CLP/F = (1.9 CLCR) + 18.4. Renal clearance also declined with decreasing renal function. Adjustments in cefpodoxime organism and on the site and severity of infection. Simulated plasma concentration-time data from this study suggest that 200 mg of cefpodoxime proxetil administered every 12 to 24 h to subjects with CLcr between 30 and 49 ml/min and 200-mg dose taken every 24 h by subjects with CLcr between 5 and 29 ml/min will maintain cefpodoxime concentration in plasma similar to those in subjects with normal renal function who receive a standard dosage mg every 12 h.

Acute Kidney Injury↗
PubMed1991

Isepamicin disposition in subjects with various degrees of renal function.

The disposition of isepamicin, an investigational aminoglycoside antibiotic, was evaluated in 30 subjects with various degrees of renal function. The subjects were divided into five groups: those with normal renal function (creatinine clearance [CLCR], greater than 80 ml/min/1.73 m2), those with mild renal insufficiency (CLCR, 50 to 80 ml/min/1.73 m2), those with moderate renal insufficiency (CLCR, 30 to 49 ml/min/1.73 m2), those with severe renal insufficiency (CLCR, 5 to 29 ml/min/1.73 m2), and those maintained on hemodialysis (CLCR, less than 5 ml/min/1.73 m2). Subjects on hemodialysis were studied both during hemodialysis and during an interdialytic period. The volumes of distribution of isepamicin were not significantly different among the five groups of patients. The total body clearance (CLP) and renal clearance (CLR) of isepamicin significantly decreased as CLCR decreased. The CLP of isepamicin and CLCR were significantly related [(COP = 0.391.[CLCR] + 1.83; r2 = 0.878)]. Nonrenal clearance of isepamicin did not differ between groups. Hemodialysis augmented the CLP of isepamicin by approximately 25-fold. The amount of isepamicin recovered in the dialysate was 60.6 +/- 15.8% of the dose administered. The maximal rebound of the isepamicin concentration in plasma after cessation of hemodialysis was observed at 0.78 +/- 0.7 h. Concentrations in plasma increased 32.7 +/- 22.9% over that measured at the end of hemodialysis. These data indicate that dosage adjustments are necessary in subjects with decreased renal function.

Adult↗
PubMed1991

Hemispheric threshold differences for motor evoked potentials produced by magnetic coil stimulation.

A brief monophasic pulse through an electromagnetic coil preferentially activates motor pathways of each hemisphere, depending on the direction of coil current flow. Using the preferred direction for each hemisphere, the minimum stimulus intensity (threshold) that evoked compound muscle action potentials in the contralateral abductor digiti minimi (ADM) muscle was significantly less for the left hemisphere than the right. Threshold for biceps on each side was significantly higher than ADM, but there was no side-to-side difference. Assessing handedness using a standard handedness index, those who had less tendency to use the right hand for everyday tasks had greater differences between hemispheres for ADM thresholds. The lower threshold of the left-hemisphere projection to hand muscles is probably related to the asymmetry of corticomotoneuronal monosynaptic connections; a greater number project to the motor neuron pool of the right- than left-hand muscles.

Action Potentials↗
PubMed1990

Renal protective effects of angiotensin-converting enzyme inhibition.

Nephron loss is a common progression of a diverse range of kidney diseases. Recent experimental models of chronic renal disease have suggested that hemodynamic and nonhemodynamic mechanisms play key roles in progressive renal injury. Extensive renal ablation in the rat was followed by development of altered glomerular hemodynamics. Albuminuria and histologic damage leading to focal glomerulosclerosis were preceded by the development of increased glomerular pressures and were prevented by interventions such as severe dietary protein restriction and angiotensin-converting enzyme (ACE) inhibitor therapy. Both experimental interventions ameliorated glomerular hypertension. It was therefore concluded that these interventions ameliorated injury by glomerular hemodynamic effect. Similar findings were obtained in a rat model of type I diabetes mellitus induced by streptozotocin in which glomerular hemodynamic factors appeared important to the development of progressive renal disease. Recent studies have suggested that nonhemodynamic factors have important roles in the progression of glomerular injury. For example, although the predominant effects of ACE inhibitor therapy appear to be hemodynamically mediated, data are emerging which suggest that these agents may also influence growth/proliferation of glomerular cells. Because hyperplasia/hypertrophy may influence glomerular susceptibility to injury, this may also be a potential mechanism whereby ACE inhibitor therapy influences glomerular damage. In addition, a variety of studies have suggested that hyperlipidemia, which is frequent accompaniment of glomerular disease, is an important modulator of glomerular injury independent of glomerular hemodynamic effects. Coagulation factors, calcium phosphorus balance, as well as the genetic susceptibility of the glomerulus to injury, all appear to contribute to progressive nephron destruction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

Flow cytometry of uveal melanomas.

Tumor cell kinetic parameters were determined for 36 uveal melanomas retained in fixed tissue sections using flow cytometric techniques and computerized morphometry. By flow cytometry the majority of cells comprising the 36 tumors were in the G0/G1 phase (55.7%). The DNA index was 1.40 +/- 0.57 units. Using Spearman's rank order correlation test, the correlation between DNA index and the inverse standard deviation of nucleolar area was found to be statistically significant. The potential usefulness of flow cytometry in predicting tumors of high malignant potential is discussed.

Cell Cycle↗
PubMed1985

The role of the right hemisphere in the control of speech prosody in propositional and affective contexts.

Sixteen right-handed adult males with localized insult to either the right or left hemisphere and five control subjects without brain damage read aloud target sentences embedded in paragraphs, while intoning their voices in either a declarative, interrogative, happy, or sad mode. Acoustical analysis of the speech wave was performed. Right-anterior (pre-Rolandic) and right-central (pre- and post-Rolandic) brain-damaged patients spoke with less pitch variation and restricted intonational range across emotional and nonemotional domains, while patients with right posterior (post-Rolandic) damage had exaggerated pitch variation and intonational range across both domains. No such deficits were found in patients with left posterior damage, whose prosody was similar to that of normal control subjects. It is suggested that damage to the right hemisphere alone may result in a primary disturbance of speech prosody that may be independent of the disturbances in affect often noted in right-brain-damaged populations.

Adult↗
PubMed1982

Ergosterol and lanosterol from Aspergillus nidulans.

Ergosterol was identified as the major free sterol of Aspergillus nidulans by thin-layer chromatography, alumina column chromatography, gas-liquid chromatography, high-performance liquid chromatography, UV spectroscopy, proton magnetic resonance spectroscopy and mass spectral analysis. Lanosterol, the initial cyclized precursor of ergosterol, was identified as a minor component of the free sterols. In the steryl ester material, however, lanosterol was usually more abundant than ergosterol, suggesting that the esters serve as storage compounds for the membrane sterol precursors.

Aspergillus nidulans↗
PubMedDate not supplied

Osmotic forces and gap junctions in spreading depression: a computational model.

In a computational model of spreading depression (SD), ionic movement through a neuronal syncytium of cells connected by gap junctions is described electrodiffusively. Simulations predict that SD will not occur unless cells are allowed to expand in response to osmotic pressure gradients and K+ is allowed to move through gap junctions. SD waves of [K+]out approximately 25 to approximately 60 mM moving at approximately 2 to approximately 18 mm/min are predicted over the range of parametric values reported in gray matter, with extracellular space decreasing up to approximately 50%. Predicted waveform shape is qualitatively similar to laboratory reports. The delayed-rectifier, NMDA, BK, and Na+ currents are predicted to facilitate SD, while SK and A-type K+ currents and glial activity impede SD. These predictions are consonant with recent findings that gap junction poisons block SD and support the theories that cytosolic diffusion via gap junctions and osmotic forces are important mechanisms underlying SD.

Computer Simulation↗