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Biomedical subjects

S Pond

Publications and source records attributed to S Pond.

16 recordsLinked to original sources
PubMed1996

Dietary fiber and laxation in postop orthopedic patients.

The addition of wheat fiber in the diet of post-surgical orthopedic patients as a means of preventing constipation was studied using a quasi-experimental design. It was hypothesized that a 20 gm supplement of All Bran and natural bran would promote spontaneous bowel movements, reduce the incidence of constipation, and thus decrease the need for elimination interventions. The results show that the study group had more spontaneous bowel movements and required fewer elimination interventions than did the control group.

Adult↗
PubMed1996

A human in vivo model for the determination of lead bioavailability using stable isotope dilution.

Beverages stored in lead-crystal glass accumulate extraordinary concentrations of lead. We obtained a lead-crystal decanter manufactured with lead from Australia, where the ratio of 206Pb/207Pb is distinctly different from that in the United States. We sought to determine the bioavailability of crystal-derived lead, using the technique of stable isotope dilution in blood. We conducted a single-dose, nonrandomized cross-over study in which participants were admitted to the Clinical Research Center twice, 1 week apart. During the first admission, subjects ingested sherry obtained from the original bottle. During the second admission, they ingested sherry that had been stored in the crystal decanter and that had achieved a lead concentration of 14.2 mu mol/l. After ingesting decanter-stored sherry, mean blood lead rose significantly (p = 0.0003) from 0.10 to 0.18 mu mol/l, while mean 206Pb/207Pb fell from 1.202 to 1.137 (p = 0.0001). On average, 70% of the ingested dose of lead was absorbed. We conclude that lead derived from crystal glass is highly bioavailable; repeated ingestions could cause elevated blood lead concentration. The technique of stable isotope dilution lends itself to the study of the bioavailability of lead in other matrices, including soil.

Adult↗
PubMed1995

Extracellular nucleotides stimulate leukocyte adherence to cultured pulmonary artery endothelial cells.

Adenosine, ATP, and various nucleotides were examined for their effects on the adherence of leukocytes to bovine pulmonary artery endothelial cells. Extracellular ATP enhanced adherence of HL-60 cells and human neutrophils to endothelial cells in a dose-dependent fashion. Maximal adherence occurred after 15 min coincubation of ATP and HL-60 cells or neutrophils with endothelial cells. ATP stimulation was mediated by direct effects on both HL-60 cells and endothelial cells. The potency profile of various nucleotides was ATP = 2-MeSATP > beta,gamma-CH2ATP, indicative of a P2y receptor. Interestingly, UTP was as potent as ATP in stimulating HL-60 cell adherence, suggesting the presence of a pyrimidine nucleotide receptor. Photoaffinity labeling of endothelial cells with 8-Az-[alpha-32P]ATP showed the presence of two ATP binding proteins of 48 and 87 kDa. ATP and 2-MeSATP inhibited binding by both proteins. Labeling of the 87-kDa protein was inhibited by beta,gamma-CH2ATP, whereas UTP blocked binding by the 48-kDa protein. Thus photoaffinity labeling experiments support the proposal that endothelial cells possess two ATP receptors, one of which is a P2u nucleotide receptor. These findings show that extracellular nucleotides enhance leukocyte adherence to endothelial cells. Nucleotide release into the extracellular space may be one mechanism of exacerbating vascular cell injury relevant to conditions such as adult respiratory distress syndrome and septic shock.

Adenosine Triphosphate↗
PubMed1993

Mianserin-induced up-regulation of serotonin receptors on normal human platelets in vivo.

The antidepressant, mianserin, is a serotonin receptor (5-HT2) antagonist and produces down-regulation of 5-HT2 and 5-HT1c receptors in the cerebral cortex of rats. In preparation for testing the validity of platelets as a model system for changes in 5-HT2 receptors during antidepressant drug treatment, mianserin (40 mg daily), was given to five human volunteers for five days, and platelets were collected on days 0, 1, 6, and 8. 5-HT2 receptor affinity and density were measured by specific binding of 125I-LSD, with and without an excess of spiperone. 5-HT uptake site affinity and density were determined by 3H-paroxetine binding, with and without an excess of fluoxetine. Platelet serotonin content was measured using high pressure liquid chromatography and electrochemical detention. Platelet 5-HT2 receptor density was increased and the ligand affinity was decreased during mianserin administration. In contrast, platelet 5-HT content was not altered significantly by mianserin administration, nor was platelet uptake site density and ligand affinity.

Analysis of Variance↗
PubMed1991

Hepatic uptake of protein-bound ligands: extended sinusoidal perfusion model.

Traditional transport models have failed to account for uptake of many protein-bound ligands by liver and other tissues when the concentration of plasma albumin or other binding protein is varied. In this paper, we extend the standard sinusoidal perfusion model to include the effects of slow dissociation of the ligand from albumin and of diffusion across extracellular barriers such as the unstirred layer. We then use experimental data for uptake of oleate from albumin solutions (1:10 molar ratio) by perfused female rat livers to test this model. Unlike the standard model, the extended model closely conformed to observed uptake rates over a wide concentration range (0.015-0.45 mM albumin). The extension, which is conceptually simple, is based on widely accepted physiological principles. It requires only the introduction of two dimensionless ratios into the standard model: the ratio of the mean unbound ligand concentration actually present within the capillary or sinusoid to its equilibrium value, and the ratio of the permeability of the membrane plus associated extracellular diffusion barriers to the permeability of the membrane alone. The resulting model simplifies to the standard sinusoidal perfusion model when both ratios approximate unity. We first develop the model for steady influx alone because our data suggest that little efflux of oleate occurred over the time course of the current study. In an appendix, we extend the model to include the effects of efflux and metabolism. The new model offers an alternative for explaining uptake kinetics of protein-bound ligands that cannot be explained by less complete traditional models.

Animals↗
PubMed1986

Hyperthermia associated with drug intoxication.

Hyperthermia (temperature of at least 40.5 degrees C for at least one hour) associated with drug intoxication was identified in 12 patients over a 5-yr period. Intoxication was due to anticholinergic drugs (tricyclic antidepressants, antipsychotics, antihistamines), CNS stimulants (phencyclidine, cocaine, 3,4-methylene dioxyamphetamine, mescaline, lysergic acid diethylamide), salicylates, or combinations of these. Hyperthermia was present in four patients on admission, but its onset was delayed up to 12 h in the remainder. Outcome of hyperthermic patients was poor: five died and four had severe permanent neurologic sequelae. Clinical signs common to patients who developed hyperthermia were increased muscular activity and absence of sweating. Five patients suffered seizures, and four did not respond to anticonvulsant medication until body temperature was lowered. Cooling did not appear to favorably affect the outcome after body temperature had remained above 40.5 degrees C for a prolonged period. Prevention of death or neurologic sequelae from drug-induced hyperthermia depends upon the recognition of risk factors and the prompt treatment of hyperthermia.

Adolescent↗
PubMed1983

An assessment of the potential testicular toxicity of 10 pesticides using the mouse-sperm morphology assay.

Dinitrobutylphenol, chlorbenzilate, atrazine, Ordram, Telone (dichloropropene), pentachlorophenol (technical and reagent grades), Benomyl, DBCP (dibromochloropropane), and carbaryl were tested over a range of 7 doses in the mouse to assess their testicular toxicity. Measures of potential toxicity were sperm morphology, sperm counts and testicular weights. Each pesticide was injected intra-peritoneally in a single dose on each of 5 days. Testicular toxicity was assessed at 35 days. None of the pesticides tested, including the known human male testicular toxin, DBCP, produced statistically significant differences in the parameters from vehicle-injected controls.

Animals↗
PubMed1982

Oleander interference in the digoxin radioimmunoassay in a fatal ingestion.

An elderly woman allegedly ingested oleander leaves and died. Ventricular arrhythmias and asystole were unresponsive to cardiopulmonary resuscitation, pharmacologic agents, and cardioversion. The patient, who had no access to digoxin, had an initial serum digoxin concentration of 5.8 ng/mL. Cross-reactivities between oleander extract and pure oleandrin and digoxin in the digoxin radioimmunoassay were 100:1 and 29,000:1, respectively. We postulate that glycosides in oleander leaves produced the elevated serum digoxin concentration. Based on an assumed volume of distribution of the oleander glycosides of 1 L/kg, the calculated lethal dose absorbed by our patient was 200 times greater than lethal doses in several animal species and corresponded to the absorption of 4 g of oleander leaves.

Aged↗
PubMed1982

Impaired metabolism of methylphenobarbital after a combined drug overdose: treatment by resin hemoperfusion.

A 38-yr-old woman who by history ingested 13 g methylphenobarbital, alcohol, and 6 g acetaminophen became comatose slowly over 4 d. Acute hepatic injury appeared to impair the oxidative N-demethylation of methylphenobarbital to its product, phenobarbital. On the eighth day after ingestion she was treated because of protracted coma with Amberlite XAD-4 resin hemoperfusion. Hemoperfusion, which removed 0.83 g methylphenobarbital and 2.10 g phenobarbital, led to transient clinical improvement. When supportive patient management fails to produce a satisfactory clinical course in a methylphenobarbital-intoxicated patient, hemoperfusion could be a useful adjunct to therapy.

Acetaminophen↗
PubMed1980

Resin hemoperfusion in ethychlorvynol overdose.

An 18-yr-old male with a severe ethchlorvynol (ECV) overdose was treated with Amberlite XAD-4 resin hemoperfusion. Plasma ECV concentration declined 33% during a 3.5-hr hemoperfusion, but rebounded substantially, peaking 6 hr later. It was estimated that 16% of ECV in the body was removed. Following hemoperfusion, plasma ECV concentrations declined linearly at a rate of 13 mg/1/day. Hemoperfusion clearance was estimated by both the traditional method, using extraction ratios across the column and column blood flow (Cl = 270 ml/min), and an alternative method, using blood concentrations during hemoperfusion and recovery of drug from the resin (Cl = 184 ml/min). The latter may provide a better estimate of hemoperfusion clearance because it is not subject to error (which can be substantial) in measurement of column blood flow. The resin completely extracted ECV from plasma, resulting in a rate of elimination 10 times that expected from endogenous processes. To aid in kinetic analysis, blood:plasma partition and protein binding of ECV in 3 normal subjects were also examined. Blood:plasma ratio averaged 0.88 +/- 0.04 and fraction free in plasma, 0.38 +/- 0.02; neither changed as a function of blood concentration between 27 and 108 mg/1. Our data indicate that removal of ECV from the overdosed patient by hemoperfusion is limited by extensive distribution in and slow redistribution from body tissues, but because of the extremely slow rate of removal by the body and the severe nature of the ECV overdose, Amberlite XAD-4 hemoperfusion may be clinically useful.

Adolescent↗
PubMedDate not supplied

Pharmacokinetics of drug overdose.

Pharmacokinetics of drugs taken in overdose may differ from those observed following therapeutic doses. Differences are due both to dose-dependent changes and to effects of drugs or pathophysiological consequences of the overdose on kinetics. Dose-dependent changes in rate and extent of absorption, bioavailability (saturation of first-pass metabolism), distribution (saturation of protein binding sites) and metabolism are discussed. Gastrointestinal motility is affected both by specific drug actions, such as delayed gastric emptying by anticholinergic drugs, and by general nervous system depression caused by many drugs. Drug-induced circulatory insufficiency may retard tissue distribution and reduce clearance. Disturbances in blood and urine pH may alter distribution and clearance of weak acids and bases. Drug-induced renal or hepatic failure can significantly decrease clearance. Hypothermia is a common complication of drug overdose and might retard distribution and also reduce clearance. The data concerning pharmacokinetics during overdose are usually incomplete and difficult to interpret. Doses and times of ingestion are uncertain, duration of blood and urine sampling is often inadequate to distinguish absorption from distribution and elimination phases, active metabolites are not measured, protein binding is not determined and clinical features of patients not adequately described. We have, however, reviewed available data for salicylate, paracetamol (acetaminophen), barbiturates, ethchlorvynol, glutethimide, chloral hydrate, tricyclic antidepressants, lithium, phenytoin, ethanol, theophylline, digoxin, amphetamine and phencyclidine.

Acetaminophen↗