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Biomedical subjects

C H Walker

Publications and source records attributed to C H Walker.

At least 109 records · Page 6Linked to original sources

The influence of dose-delivery time interval on neonatal plasma pethidine levels.

Plasma pethidine levels were determined by RIA during the first 24h of life in 126 neonates whose mothers had received a single intramuscular dose of 100-150 mg pethidine HCl 0.25 to 19.5 h before delivery. The mean (geometric) maternal and cord venous plasma pethidine concentration and the neonatal capillary plasma levels at 0.5, 1.5 and 12-24 h expressed per unit dose were 125, 98, 71, 59 and 23 ng/ml per mg/kg respectively. The mean (+/- S.E.M.) cord: maternal plasma concentration ratio was 0.741 +/- 0.036 (n = 40). The ratio was significantly correlated with the dose-delivery interval, r = 0.42, p less than 0.01. The pethidine concentration in cord and in neonatal capillary plasma was significantly correlated to the weight related dose, r = 0.25 to 0.48, p less than 0.01. Cord venous levels of pethidine rose rapidly after drug administration but neonatal capillary levels increased slowly to reach peak levels at 2 to 5 h before declining over the next 15 to 18 h. The maternal plasma pethidine half-life, 5.59 h was considerably shorter than that observed in the newborn, 15.94 h.

Delivery, Obstetric↗

The assay of microsomal epoxide hydrolase in normal and pathological human liver.

Samples of normal and pathological human liver were assayed for microsomal epoxide hydrolase activity using the chlorinated epoxide HEOM as substrate. The enzyme activity in liver samples from normal patients was 72.3 +/- 9.8 nmoles mg protein-1.min-1, which is comparable to the highest values recorded in mammals, and much higher than those found in rats and mice. A microassay procedure was developed to enable the estimation of activity in needle biopsy samples (5-20 mg), obtained from patients with normal and diseased livers. Three epileptic patients who had received regular doses of phenobarbitone and/or phenytoin showed activities significantly higher than those found in all other samples (P less than 0.01). These appeared to be examples of enzyme induction. Assays were also performed on samples from six patients with alcohol-related liver disease and one patient with hepatocellular carcinoma. The role of epoxide hydrolase in the metabolism of carcinogenic epoxides is discussed in relation to these findings.

Adult↗

A study of the hepatic microsomal epoxide hydrolase in sea birds.

1. Epoxide hydrolase activities were measured in six species of sea birds using the chlorinated epoxide HEOM as substrate. 2. The activities found fell within the general range for birds, and there were no clear sex or species differences. 3. Relatively low activities were found in liver microsomes of female puffins early in the breeding season, but high activities were found in 11,000 g precipitates from these individuals. Apart from this no correlations were found between activity and time of year, PCB residues or geographical location. 4. These results are discussed in relation to mono-oxygenase activities in the same samples.

Animals↗

A study of the hepatic microsomal monooxygenase of sea birds and its relationship to organochlorine pollutants.

1. The levels of hepatic microsomal monooxygenase in sea birds were determined using organochlorine substrates. Levels of cytochrome P450 and organochlorine residues were also measured. 2. The razorbill (Alca torda) and puffin (Fratercula arctica) showed highly variable activities which were resolved into multiple peaks on frequency diagrams. 3. The most active individuals amongst razorbills were early season females with large ovaries. 4. The properties of monooxygenase from individuals of low and high activity were compared. 5. The results are discussed in relation to PCB pollution.

Animals↗

Metabolism and route of excretion of the chloro-cyclodiene HCE in the pigeon.

Male feral pigeons were fitted with re-entrant bile duct cannulae, or were colostomized to facilitate the separate collection of urine and feces. After administration of 15 mg kg(-1) of [14C]-HCE by intraperitoneal injection, collections of bile and urine were made to determine the routes of excretion and the major metabolites. Within seven hrs the percentages of injected 14C excreted were 16.2 2.9% in the urine of colostomized birds and 12.8 1.1% in the bile of cannulated birds. Since the rate of elimination of 14 C in the feces of colostomized birds was very low (29% dose in 12 days) compared with 59% in urine, apparently some biliary metabolites were reabsorbed from the gut prior to elimination in urine. Nearly all excreted material was in conjugated form. Biliary conjugates were predominantly glucuronides (greater than 84% of total 14C) whereas 96% of the conjugated material in urine was sulfate. Initial metabolism was predominantly oxidative with the formation of a monohydroxy epoxide (HHC), which was subsequently converted into two secondary metabolites (endo-HHC and dihydroxy-HCE). In contrast to other species, no measurable quantity of trans-diol was formed. The same pattern of initial metabolism was found in hepatic microsomes. The metabolism and excretion of HCE is slower in the pigeon than in the male rat, thus providing further evidence for the limited capability of the species to perform certain detoxifying transformations.

Animals↗

A study on the toxicity and the biochemical effects of ethylene dibromide in the Japanese quail.

1. The acute oral LD50 and chronic LC50 toxicity values for ethylene dibromide (EDB) were estimated for japanese quail. 2. Single sub-acute oral and intraperitoneal doses of EDB (1/2 LD50) and chronic oral doses of EDB (1/3 LC50) were administered to quail in order to characterise the sub-lethal effects of EDB residues. 3. At 24 h after sub-acute dosing, relative liver weight, plasma aspartate aminotransferase (AT) [EC 2.6.1.1] and L-iditol (sorbitol) dehydrogenase (SDH) [EC 1.1.1.14] were elevated and decreases were found in hepatic total lipid, total protein, AT and glutamic dehydrogenase (NAD (P)+) (GDH) and plasma cholinesterase (ChE) [EC 3.1.1.8] and total lipid. 4. Following chronic administration, elevations in relative liver weight, plasma ChE and total lipid, haemoglobin and haematocrit were found and hepatic AT, GDH and total lipid were decreased. 5. The changes in hepatic and plasma enzymes and constituents are discussed in relation to possible biphasic effects resulting from EDB exposure.

Acetylcholinesterase↗

beta-Thromboglobulin levels in plasma of jaundiced neonates exposed to phototherapy.

It has been suggested that changes take place in human platelets when they are exposed to fluorescent light of 10.8W/m2/sec at 460 nm. Loss of ability to aggregate and increase in turnover rate have been reported. However, studies of the effect of fluorescent light on adult platelets when exposed to the level of irradiance used clinically (3.5W/m2/sec) for 60 min did not reveal this effect. A study was therefore designed to compare the effects of bilirubin and phototherapy alone and in combination on cord and adult blood platelets obtained from jaundiced neonates. Using beta-thromboglobulin as the indicator of platelet damage, no significant change was found in platelet poor plasma from cord or adult blood following exposure to bilirubin and/or light, nor was any change found in the plasma of jaundiced neonates before and after therapy. Although the duration of exposure to light in this study was short, the results suggest that the lower levels of irradiance used clinically are not harmful to platelets and that the results of studies done with three times as much irradiance have little clinical relevance.

Beta-Globulins↗

Naloxone pharmacokinetics in the newborn.

1 Plasma naloxone levels were determined by RIA over a period of 6--36 h in three groups of neonates, (1) those given 35 microgram i.v. (n = 6), (2) those given 70 microgram i.v. (n = 6) and (3) those given 200 microgram i.m. (n = 17) naloxone HCl within 1 min of birth. 2 After intravenous administration of 35 and 70 microgram of naloxone peak levels of 4--15 ng/ml and 9--20 ng/ml respectively were reached in 5--40 min and the mean plasma half-life after both doses was 3.1 +/- 0.5 h. 3 Peak levels of 7--35 ng/ml were reached 0.5 to 2 h after intramuscular administration of 200 microgram. The fall in concentration after this was consistently biphasic with the levels declining rapidly between one and four hours and then slowly from four hours onwards. 4 Plasma levels at 24--36 h after i.m. administration were as high as they were 4 h after i.v. administration of 35 microgram and this may account for the prolonged duration of action when this route is used.

Half-Life↗