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Biomedical subjects

M R Silver

Publications and source records attributed to M R Silver.

33 records · Page 2Linked to original sources
PubMed1990

Intrinsic gating of inward rectifier in bovine pulmonary artery endothelial cells in the presence or absence of internal Mg2+.

Inward rectifier (IR) currents were studied in bovine pulmonary artery endothelial cells in the whole-cell configuration of the patch-clamp technique with extracellular K+ concentrations, [K+]o, ranging from 4.5 to 160 mM. Whether the concentration of free Mg2+ in the intracellular solution, [Mg2+]i, was 1.9 mM or nominally 0, the IR exhibited voltage- and time-dependent gating. The IR conductance was activated by hyperpolarization and deactivated by depolarization. Small steady-state outward IR currents were present up to approximately 40 mV more positive than the K+ reversal potential, EK, regardless of [Mg2+]i. Modeled as a first-order C in equilibrium O gating process, both the opening rate, alpha, and the closing rate, beta, were exponentially dependent on voltage, with beta more steeply voltage dependent, changing e-fold for 9 mV compared with 18 mV for an e-fold change in alpha. Over all [K+]o studied, the voltage dependence of alpha and beta shifted along with EK, as is characteristic of IR channels in other cells. The steady-state voltage dependence of the gating process was well described by a Boltzmann function. The half-activation potential was on average approximately 7 mV negative to the observed reversal potential in all [K+]o regardless of [Mg2+]i. The activation curve was somewhat steeper when Mg-free pipette solutions were used (slope factor, 4.3 mV) than when pipettes contained 1.9 mM Mg2+ (5.2 mV). The simplest interpretation of these data is that IR channels in bovine pulmonary artery endothelial cells have an intrinsic gating mechanism that is not due to Mg block.

Animals↗
PubMed1988

Potassium currents in rat type II alveolar epithelial cells.

1. Type II alveolar epithelial cells isolated from adult rats and grown in primary culture were studied using the whole-cell configuration of the gigohm-seal voltage clamp technique. 2. The average specific capacitance of type II cells was 2.5 microF/cm2, suggesting that type II cell membranes in vitro are irregular, with an actual area more than twice the apparent area. 3. Most type II cells have time- and voltage-dependent outward currents carried by potassium ions. Potassium currents activate with a sigmoid time course upon membrane depolarization, and inactivate during maintained depolarization. The average maximum whole-cell K+ conductance was 1.6 nS. 4. Two distinct types of K+-selective channels underlie outward currents in type II cells. Most cells have currents resembling delayed rectifier K+ currents in skeletal muscle, nerve and immune cells. A few cells had a different type of K+ conductance which is more sensitive to block by tetraethylammonium ions, has faster 'tail currents', and activates at more positive potentials. 5. In some experiments, individual type II cells were identified by staining with phosphine, a fluorescent dye which is concentrated in lamellar bodies. Both types of K+ channels were seen in type II cells identified with this dye. 6. Phosphine added to the bathing solution reversibly reduced K+ currents and shifted K+ channel activation to more positive potentials. Excitation of phosphine to fluoresce reduced irreversibly K+ currents in type II cells. The usefulness of phosphine as a means of identifying cells for study is discussed.

Action Potentials↗
PubMed1987

Pentoxifylline in end-stage renal disease.

Little information is available about the clearance of pentoxifylline and its metabolites in renal failure. Consequently, when a dialysis patient required this drug, we started at a low dose and gradually increased the dosage while monitoring the patient for signs or symptoms of toxicity and following plasma concentrations of parent drug and its metabolites. Our patient appeared to develop evidence of drug toxicity after about six days on two-thirds of the usual recommended adult dose of the drug. The pentoxifylline half-life and apparent half-life of metabolite I were both substantially prolonged as compared with data from healthy volunteers. Both accumulated rapidly in plasma. Concentrations of metabolites IV and V were also very high.

Adult↗
PubMed1987

High-performance liquid chromatographic characterization of neurophysins in chronic renal failure.

Levels of immunoreactive (IR) oxytocin (OT)-associated or estrogen-stimulated neurophysin (ESN) and vasopressin-associated or nicotine-stimulated neurophysin (NSN) were measured in plasma of patients with chronic renal failure before and after hemodialysis (HD) and intermittent peritoneal dialysis (IPD), and during continuous ambulatory peritoneal dialysis (CAPD). ESN-IR in 17 patients before HD was 24.4 +/- 2.7 ng/ml (mean +/- SEM) and increased after HD to 33.2 +/- 4.1 ng/ml (P less than 0.001). ESN-IR in 17 patients with CAPD was 15.2 +/- 3.4 ng/ml, significantly lower than in patients undergoing HD, P less than 0.001. In patients receiving IPD (n = 6), ESN was 11.6 +/- 3.7 ng/ml and did not change significantly after IPD. Levels of ESN in patients with renal failure were increased compared with levels in normal individuals, 1.0 +/- 0.1 ng/ml. Levels of ESN were not correlated with laboratory parameters that may be abnormal in renal failure. NSN levels in 16 of 17 patients undergoing HD were 3.2 +/- 0.34 ng/ml and in 14 of 17 patients with CAPD were 2.9 +/- 0.4 ng/ml, respectively. ESN before HD (r = 0.63, P less than 0.01), after HD (r = 0.85, P less than 0.001), and in patients with CAPD (r = 0.83, P less than 0.001) and IPD (r = 0.81, P less than 0.05) correlated significantly with an OT-like peptide previously found to be increased in renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

The syndrome of spontaneous iliac arteriovenous fistula: a distinct clinical and pathophysiologic entity.

While the development of a spontaneous iliac arteriovenous fistula is an uncommon complication of arteriosclerotic aneurysmal disease, its association with a distinct clinical syndrome allows timely operative intervention for this potentially life-threatening event. A review of cases reported in the literature reveals a triad of symptoms consistently associated with the presence of a spontaneous iliac arteriovenous fistula: high-output cardiac failure of precipitous onset, a pulsatile abdominal mass accompanied by a thrill and bruit, and unilateral lower-extremity ischemia or venous engorgement. Survival may be anticipated if an aggressive diagnostic and operative approach is employed.

Aged↗
PubMed1985

Severe reactions during hemodialysis.

Severe reactions during dialysis occurred in 1.7% of hemodialysis patients. Respiratory distress, agitation, pruritus, and alterations in BP were the dominant clinical findings, and one patient suffered a respiratory arrest. It is not clear whether this syndrome is due to toxic substances or to an allergic reaction, although the presence of eosinophilia in three of five affected patients would suggest the latter mechanism. Disconnecting the patient from the extracorporeal circuit invariably improved the symptoms. Current evidence implicates the dialyzer as the most likely culprit, and our experience suggests that none of the commonly used dialysis membranes are truly biocompatible.

Adolescent↗
PubMed1985

Effects of end-stage renal disease and aluminum hydroxide on temazepam kinetics.

The kinetics of temazepam, 30 mg, were evaluated in 11 patients with end-stage renal disease. Age ranged from 18 to 65 years. On two occasions separated by 1 week, single oral 30 mg doses of temazepam were given once with water (TM) and once with 3600 mg aluminum hydroxide gel (TM + AHG). There were no significant differences in the maximum plasma concentration, the time to reach maximum concentration, or elimination rates between TM and TM + AHG dosing. In approximately half the subjects there were secondary temazepam peak concentrations. In the remaining subjects, temazepam elimination was biphasic, with the terminal t1/2 ranging from 11 to 77 hours. There was a lag time before absorption in all subjects. The percent free temazepam in plasma from dialysis subjects ranged from 4.4% to 8.8% (mean = 5.9%). Compared with literature reports of subjects with normal renal function, the maximum plasma concentration was lower and the percent free temazepam was higher in dialysis subjects. When sedation score was plotted against plasma temazepam concentration, there was clockwise hysteresis consistent with tolerance or adaptation to effects of the drug. Thus aluminum hydroxide gel does not affect temazepam absorption. The clinical significance of the low plasma concentrations and high free temazepam fraction in dialysis subjects is uncertain.

Absorption↗
PubMed1985

Effects of end stage renal disease and aluminium hydroxide on triazolam pharmacokinetics.

Triazolam 0.5 mg was administered to 11 dialysis patients and 11 age, weight and sex matched controls. Peak plasma concentrations (Cmax) were higher in control subjects, but there were no other differences between the groups. When dialysis patients took triazolam with 3600 mg aluminum hydroxide suspension, Cmax and AUC were increased into the range observed in control subjects. It appears that triazolam can be used at normal doses in patients with renal dysfunction, without regard to interaction with aluminum hydroxide gel, or to alterations in elimination.

Adolescent↗
PubMed1984

Triazolam protein binding and correlation with alpha-1 acid glycoprotein concentration.

On two occasions separated by a minimum of 1 wk, plasma was obtained from 12 patients (aged 18 to 73 yr) on dialysis after an overnight fast. Samples were assayed for albumin and alpha 1-acid glycoprotein (AGP) concentrations. 14C-Triazolam was added to each sample to a final concentration of 5 ng/ml. Protein binding was determined by equilibrium dialysis. Unbound triazolam ranged from 6.4% to 15.4% (mean = 10.0%). AGP concentrations ranged from 71.8 to 205.1 mg% (mean = 123.4 mg%). Triazolam binding ratio (bound/unbound concentration) correlated with AGP concentration (r2 = 0.69) but not with albumin concentration, age, or sex. This correlation was verified by adding AGP in varying amounts to control plasma.

Adolescent↗
PubMed1984

Peritoneal eosinophils during intermittent peritoneal dialysis.

Peritoneal eosinophil counts were investigated in 61 intermittent dialysis patients over the course of 1 year. The peritoneal eosinophil percentage fell from 18 +/- 2% (mean +/- SEM) in the first 2 months of dialysis to 3 +/- 0.4% after 6 months of dialysis. Absolute eosinophils per cubic millimeter fell from 586 +/- 126 to 61 +/- 18 (p less than 0.01 for both percentage and absolute values). There was a wide range in the mean eosinophil percentages per patient in the first 6 months of dialysis (0-84%) that narrowed to 0-9% after 6 months. The majority of the high initial eosinophil counts resolved after 2 months. Peripheral eosinophilia was seen in 8 of the 10 patients with the highest mean peritoneal eosinophil percentages during the first 2 months of dialysis. Patients who developed peritonitis had a significantly lower percentage of eosinophils in the first 1.5 months of dialysis than patients who did not develop peritonitis. At the time of diagnosis of peritonitis, the peritoneal eosinophil count was near zero. 4 cases of peritoneal eosinophilia which developed after antibiotic therapy are described.

Adult↗
PubMed1980

Active site radioimmunoassay for human urokallikrein and demonstration by radioimmunoassay of a latent form of the enzyme.

A radioimmunoassay specific for the active site in urokallikrein has been developed with a monospecific antibody that neutralizes the enzymatic activities of urokallikrein and a radioligand purified so as to maintain the active site. In order to favor the involvement of the antibody with high affinity for the active site in the competition between urokallikrein in biological fluids and radiolabeled urokallikrein, the radioligand was separated from denatured radiolabeled urokallikrein by affinity chromatography for the active site. The concentration of specific IgG used in the assay bound approximately 80% of the radioligand, which was displaced in a dose-related fashion by 0.2 to 2.5 ng of the unlabeled urokallikrein. When random urine samples from 21 healthy volunteers were assessed for endogenous urokallikrein by both active site radioimmunoassay and kinin generation, there was a linear relationship between the results of the two assays with a correlation coefficient of 0.89. A combined correlation plot of the results of the bioassay and the active site radioimmunoassay for the 21 urine samples before and after trypsin activation gave a linear regression line with a correlation coefficient of 0.91. The finding that trypsin activation increased the urokallikrein concentration of urine to a similar extent in both the radioimmunoassay and the bioassay means that latent urokallikrein was not detected until its active site was uncovered.

Animals↗