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Biomedical subjects

R D White

Publications and source records attributed to R D White.

At least 217 records · Page 12Linked to original sources
PubMed1982

The bioactivation of 1,2-dibromoethane in rat hepatocytes: covalent binding to nucleic acids.

Isolated rat hepatocytes metabolized 1,2-dibromoethane (EDB) to reactive intermediates which covalently bound to cellular nucleic acids. DNA isolated from hepatocytes that had been incubated with [14C]EDB (80 microM) was alkylated with a specific binding of 0.6 nmol/mg DNA. RNA exhibited a greater specific alkylation with 2.1-3.0 nmol bound/mg. High concentrations of EDB (greater than 500 microM) depleted the concentration of hepatocellular glutathione, but binding of [14C]EDB equivalents to nucleic acids occurred at concentrations which had little effect on glutathione levels. Diethylmaleate (750 microM) decreased the binding of [14C]EDB equivalents to nucleic acids by 50%, but SKF-525A (200 microM) did not decrease this binding to nucleic acids. Although both hepatic microsomal and cytosolic fractions catalyzed the covalent binding of [14C]EDB equivalents to calf thymus DNA, the degree of binding was 12 times greater when cytosolic enzymes were used. The results suggest the involvement of glutathione-S-transferases in the bioactivation of EDB to species that covalently bind to DNA.

Alkylation↗
PubMed1982

Cardiovascular effects of protamine sulfate in man.

Systemic hypotension is commonly observed in association with the administration of protamine after cardiopulmonary bypass. Previous studies have not conclusively demonstrated whether protamine induces its effect by altering myocardial performance or by changing systemic vascular resistance (SVR) or both. To elucidate the hemodynamic effects of protamine sulfate administration (150 mg/m2 body surface area), we studied 22 patients following cardiopulmonary bypass. In Group I (N = 8) protamine was infused over 30 seconds and while in Group II (N = 8), over 60 seconds. Group III (N = 6) received calcium chloride (20 mg/kg) prior to protamine administration. The hemodynamic response was assessed by continuous recording of myocardial contractile element velocity (maximal value-Vpm), aortic blood flow, systemic and pulmonary arterial and right atrial pressures, and electrocardiogram. A significant (p less than 0.05) decrease in the systolic, diastolic and mean blood pressure was observed in all groups. A significant increase in cardiac index and a significant decrease in SVR was observed in all groups. A small depression in Vpm was detected in those patients who experienced a mean blood pressure fall greater than 10 mm Hh. Heart rate and left ventricular end-diastolic pressure (LVEDP) did not change significantly. The response to protamine sulfate among the three groups was similar. These results demonstrate that protamine-induced hypotension is primarily the result of peripheral vasodilatation only partically compensated by an increase in cardiac index. In some patients, these changes were associated with a small decline in myocardial contractile state. Hemodynamic changes were transient (less that 3 to 4 minutes), unrelated to the rate of administration, and not prevented by preinjection of calcium chloride.

Blood Pressure↗
PubMed1981

Characterization of the hepatic DNA damage caused by 1,2-dibromoethane using the alkaline elution technique.

The damage to hepatic cell DNA caused by i.p. administration of 1,2-dibromoethane (EDB) was studied in male Swiss Webster mice. Three hours after treatment, hepatic nuclei were isolated and damage to DNA assessed by the alkaline elution technique. The method for isolation of the nuclei preserved the integrity of the DNA and in addition it was found that the purified nuclei could be frozen for at least 1 week with no detectable damage to the DNA. EDB administration (25-75 mg/kg) resulted in a dose-dependent increase in DNA single-strand breaks. More DNA single-strand breaks were detected when lysed nuclei were preincubated in the alkaline eluting solution prior to analysis. The presence of these alkali-labile sites suggests that the DNA strand breaks result, in part, from the lability of DNA sites alkylated by EDB. There was no evidence of EDB induced DNA-DNA cross-links or DNA-protein cross-links. The use of isolated hepatic nuclei as a sample for alkaline elution analysis may be a useful technique for studying the nature of DNA damage induced in vivo by carcinogens.

Animals↗
PubMed1981

Are surveillance of resistant enteric bacilli and antimicrobial usage among neonates in a newborn intensive care unit useful?

From March 1976 through December 1978, the prevalence of ampicillin- and gentamicin-resistant enteric bacilli was monitored in fecal cultures of neonates in an intensive care unit. Substantial fluctuations in colonization rates were observed which did not correlate with the occurrence of sepsis due to these organisms nor with variations in antibiotic use. This experience suggests that the availability of these surveillance data did not result in more effective control of neonatal sepsis due to enteric bacilli.

Ampicillin↗
PubMed1980

The inhibition of premature labor with indomethacin.

We administered indomethacin orally for the treatment of premature labor in a prospective, randomized, double-blind fashion, and all infants were followed up. Indomethacin was significantly more effective than placebo in inhibition of premature labor during a 24-hour course of therapy, with treatment failure during therapy occurring in only one of 15 indomethacin-treated patients compared to nine of 15 placebo-treated patients (p less than 0.01). Mean plasma concentrations of indomethacin were approximately 0.8 micrograms/ml at both 4 and 12 hours after administration. Mean plasma levels of 15-oxo-13,14-dihydroprostaglandin F2 alpha (PGFM) were similar in the two groups before treatment, decreased markedly in the indomethacin group by 4 hours, and were not detected at 12 hours in all but the one indomethacin-treated patient who was delivered within 24 hours. Patients in the placebo group who were delivered prematurely had higher pretreatment PGFM levels (mean +/- SE, 83 +/- 18 pg/ml, n = 9) than the patients who responded to placebo (25 +/- 6 pg/ml, n = 6) (p less than 0.05). There was no difference between the indomethacin and placebo groups with respect to gestational age at delivery, birth weight, and neonatal morbidity and deaths. In particular, we found no evidence of premature closure of the ductus arteriosus, pulmonary hypertension, or increase in bleeding problems among the infants exposed to indomethacin in utero. Although no difference in neonatal outcome was observed in this small number of patients, it would seem prudent still to consider indomethacin as an experimental therapy.

Dinoprost↗
PubMed1980

Occupational lead exposure, nephropathy, and renal cancer.

A 48-year-old lead worker was found to have a cystic renal carcinoma during an evaluation of his occupational lead poisoning. Clinical studies showed elevated blood lead levels, impaired urinary concentrating ability, and reduced creatinine clearance. Histologic and electron microscopic studies showed this cystic tumor to be similar to renal carcinomas observed in animals with prolonged lead exposure. Lead content of the tumor was elevated (2.49 micrograms/gm) in comparison with adjacent renal tissue and with normal adult levels. In light of previous animal studies, this case adds increased evidence to the concern over the carcinogenic potential of prolonged lead exposure.

Adenocarcinoma↗
PubMed1980

Muscarinic receptors in rat sympathetic ganglia.

1 Potential changes in isolated superior cervical ganglia of the rat produced by muscarinic-receptor agonists were recorded by an extracellular ;air-gap' method.2 Muscarinic agonists produced a delayed low-amplitude ganglion depolarization, frequently preceded by a hyperpolarization. Potentials were enhanced by reducing [K(+)](o) or [Ca(2+)](o).3 Mean ED(50) values (muM) for depolarization at 25 degrees C were: oxotremorine 0.004, methylfurmethide 0.11, (+/-)-muscarine 0.24, furmethide 1.56, pilocarpine 4.81 and AHR-602 (N-benzylpyrrolidylacetate methobromide) 10.8. Responses produced by oxotremorine, pilocarpine and AHR-602 showed some characteristics of ;partial agonism'. ED(50) values (muM) for choline esters (measured in the presence of 2.5 mM hexamethonium) were: acetylcholine 3.2, methacholine 59 and bethanechol 78.4 Responses to muscarine were antagonized by hyoscine (K(I) 0.49 nM) atropine (K(I) 0.24 nM) methylscopolamine (K(I) 0.09 nM) lachesine (K(I) 0.15 nM) and (weakly) by hexamethonium (K(I) 0.2 mM). Propylbenzilylcholine mustard produced irreversible antagonism with an apparent onset rate constant of 2 x 10(5) M(-1)S(-1).5 Depolarization was accompanied by facilitation of submaximal ganglionic transmission.6 Muscarine (1 to 100 muM) initially reduced, then increased, the rate of (86)Rb(+)-efflux from isolated ganglia at both 6 and 120 mM [K(+)](o). These effects were reduced by 1 muM hyoscine.7 No consistent change in the amounts of cyclic 3',5'-guanosine monophosphate in isolated ganglia accompanying muscarinic depolarization could be detected.8 Mean against ED(50) values (muM) for contracting the rat isolated ileum were: oxotremorine 0.012, methylfurmethide 0.29, (+/-)-muscarine 0.48, pilocarpine 7.8 and AHR-602 9.9. Mean antagonist K(I) values (nM) were: hyoscine 0.17, atropine 0.34 and lachesine 0.27.9 It is concluded that ganglionic muscarinic receptors are quite similar to ileal receptors in terms of agonist ED(50) and antagonist K(I) values, and that the major difference between them lies in the greater ;efficacy' of certain agonists (pilocarpine, AHR-602 and McN-A-343) on the ganglion.

Animals↗