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Biomedical subjects

J Thomas

Publications and source records attributed to J Thomas.

At least 775 records · Page 43Linked to original sources
PubMed1978

Hepatic fatty acid oxidation and ketogenesis after clofibrate treatment.

The effect of clofibrate treatment on hepatic ketogenic capacity was studied in rats. Ketogenesis from octanoate and oleate was increased 2- and 4,5-fold, respectively, in hepatocytes from fed, treated rats. In contrast to controls ketogenic rates did not increase upon starvation. While ketogenesis from oleate was higher in fed, treated animals than in fasted controls, endogenous ketogenesis was lower and increased upon starvation. Ketogenesis from octanoate and oleate was stimulated approx. 2-fold in homogenates from treated animals. Labeled pyruvate and succinate oxidation was unaltered. [1-14C]Oleate oxidation was severely inhibited by cyanide, both in homogenates from controls and treated animals. Clofibrate caused a 3-fold increase in hepatic carnitine levels. Catalase and glutamate dehydrogenase activities were also increased by the drug. Cytochrome c oxidase did not change. Despite their increased ketogenic capacity hepatocytes from treated rats esterified as much oleate as controls. The increased oxidation was matched by an increased oleate uptake. Plasma ketones were increased 2-fold in fasted, treated animals. Plasma free fatty acids were unaffected. It is concluded that the enhanced ketogenic capacity induced by clofibrate is the result of an increase in mitochondrial beta-oxidation, an increase in the activity of carnitine palmitoyltransferase and possibly of the observed increases in hepatic carnitine content and fatty acid uptake.

Animals↗
PubMed1978

The pharmacokinetics and metabolism of the anilide local anaesthetics in neonates. I. Lignocaine.

The pharmacokinetics and metabolism of lignocaine in premature neonates was studied after subcutaneous administration. The collection of serial urine together with a limited number of blood samples from neonates enabled simultaneous computer fitting of data to a pharmacokinetic model. The disposition kinetics of lignocaine in four neonates were compared with similar data reported for adults. Neonates had prolonged t1/2 (neonate mean: 3.16 h; adult mean: 1.80 h), and an increased total volume of distribution (neonate mean: 2.75 l/kg; adult mean: 1.11 l/kg) compared with adults. Total plasma clearance (Cltp) normalised on body weight showed no significant difference between neonates (mean: 0.610 l/h/kg) and adults (mean: 0.550 l/h/kg). The urinary excretion of lignocaine and several of its metabolites was studied in 8 neonates and 11 adults. Neonates were shown to excrete much more unchanged lignocaine (mean: 19.67%) compared with adults (mean: 4.27%) and the proportion of the dose excreted as 4-hydroxyxylidine is considerably reduced in neonates (neonate mean: 8.89%; adult mean: 63.78%). The use of the two pharmacokinetic parameters, t1/2 and Cltp, as indices of drug elimination ability are discussed.

Adult↗
PubMed1978

Disposition of meperidine in pregnancy.

Plasma concentration-time profiles of meperidine after intravenous administration to 7 pregnant women during labor were investigated. There was considerable interpatient variation in initial plasma concentrations of meperidine and its volume of distribution. When the data in the literature on the disposition of meperidine in nonpregnant subjects were used for comparison, it was found that the initial dilution volume (V1), the volume of distribution at steady-state (Vss), and the apparent volume of distribution during the terminal exponential phase of drug elimination (Vbeta) were less (p less than 0.05) in pregnant subjects than in healthy nonpregnant control subjects but were not significantly different in pregnant subjects and nonpregnant surgical patients. Mean total systemic blood clearance was also significantly less in the pregnant subjects (843 ml/min) than previously reported for healthy nonpregnant control subjects (1,465 ml/min). The blood/plasma concentration ratio of meperidine in pregnant women (0.940) was higher than that in control subjects (0.768; p less than 0.01). Placental transfer of meperidine was investigated in 4 of the patients; in 2 the concentration of the drug was greater in cord plasma than in maternal plasma. Further study is indicated.

Adolescent↗
PubMed1978

Protein binding of tolmetin.

The protein binding of the new nonsteroidal anti-inflammatory agent tolmetin to human serum albumin (HSA) and to the plasma of 8 healthy subjects was studied by equilibrium dialysis at 37 degrees and pH 7.4 with 14C-tolmetin. Over the total concentration (Ct) range 3.0 to 28.7 microgram/ml (therapeutic range), the fraction of tolmetin unbound to 4% HSA was largely invariant at 0.3%. At 100 microgram/ml the unbound fraction rose to 0.8 and at 434 microgram/ml to 3.6%. Within the therapeutic concentration range, tolmetin binding to 0.4% HSA was reduced in accordance with the law of mass action and at Ct = 26.2 microgram/ml, 10.5% was free. Analysis of the 0.4% HSA data showed tolmetin had 3 classes of binding sites (n1 = 1, K1 = 8.3 X 10(5) M-1; n2 = 4, K2 = 2.4 X 10(4) M-1; n3 = 44, K1 = 7.9 X 10(1) M-1). By studying the binding to 0.4% HSA at 23 degrees, it was established that the free energy change in binding for the first two classes of sites was entirely entropic in nature. Albumin accounted for almost all the binding of tolmetin in human plasma. The effect of other drugs, the tolmetin metabolite McN 2987 (5-p-carboxybenzoyl-1-methylpyrrole-2-acetic acid), tryptophan, and oleic acid on tolmetin binding to 4% HSA was studied using ultrafiltration and 14C-tolmetin. Aspirin and salicyclic acid decreased tolmetin binding and a combination of aspirin and salicyclic acid exerted a synergistic displacing effect. Indomethacin and ibuprofen had no effect while phenylhbutazone and acetaminophen increased tolmetin binding slightly. Tolmetin binding was decreased slightly by McN 2987 and tryptophan and markedly increased by oleic acid. McN 2987 was not bound as extensively as tolmetin. Binding of 14C-tolmetin to the plasma of 4 arthritic patients was studied by ultrafiltration and found to be less than to normal plasma and 4% HSA. Distribution of tolmetin in the whole blood of 8 healthy subjects using a centrifugation technique showed that the drug was not taken up by red blood cells at therapeutic concentrations.

Adult↗
PubMed1978

Preoperative diagnosis of unilateral multicystic kidney with hydropelvis.

We present 2 patients with congenital unialteral multicystic kidney disease with hydropelvis. In the first patient the diagnosis was made by precutaneous puncture of a renal cyst followed by injection of contrast medium; in the second the diagnosis was confirmed by percutaneous puncture of the renal pelvis and injection of contrast medium, although an earlier ultrasonic examination had been strongly suggestive. Since in this condition the cysts and the renal pelvis communicate, either can be punctured to make the diagnosis. The procedures herein described are definitive for the diagnosis and should be followed whenever the urologist desires such a diagnosis.

Biopsy, Needle↗
PubMed1978

Initial organic products of assimilation of [N]ammonium and [N]nitrate by tobacco cells cultured on different sources of nitrogen.

Glutamine is the first major organic product of assimilation of (13)NH(4) (+) by tobacco (Nicotiana tabacum L. cv. Xanthi) cells cultured on nitrate, urea, or ammonium succinate as the sole source of nitrogen, and of (13)NO(3) (-) by tobacco cells cultured on nitrate. The percentage of organic (13)N in glutamate, and subsequently, alanine, increases with increasing periods of assimilation. (13)NO(3) (-), used for the first time in a study of assimilation of nitrogen, was purified by new preparative techniques. During pulse-chase experiments, there is a decrease in the percentage of (13)N in glutamine, and a concomitant increase in the percentage of (13)N in glutamate and alanine. Methionine sulfoximine inhibits the incorporation of (13)N from (13)NH(4) (+) into glutamine more extensively than it inhibits the incorporation of (13)N into glutamate, with cells grown on any of the three sources of nitrogen. Azaserine inhibits glutamate synthesis extensively when (13)NH(4) (+) is fed to cells cultured on nitrate. These results indicate that the major route for assimilation of (13)NH(4) (+) is the glutamine synthetase-glutamate synthase pathway, and that glutamate dehydrogenase also plays a role, but a minor one. Methionine sulfoximine inhibits the incorporation of (13)N from (13)NO(3) (-) into glutamate more strongly than it inhibits the incorporation of (13)N into glutamine, suggesting that the assimilation of (13)NH(4) (+) derived from (13)NO(3) (-) may be mediated solely by the glutamine synthetase-glutamate synthase pathway.

Journal Article↗
PubMed1978

Effect of ulcer healing on the prognosis of chronic gastric uler. Four-year follow-up.

Eighty three patients were followed-up for four years after an admission to hospital with a chronic gastric ulcer proven by radiology (index ulcer). The index ulcer healed completely in 50 patients, but was unhealed at the time of discharge in the other 33. Significantly fewer patients whose index ulcer was healed compared with those whose ulcer was unhealed at discharge had had a recurrence by one (p < 0.05), two, three and four years' (p < 0.01) follow-up. Moreover, the rate of recurrence was significantly greater for those patients with unhealed, compared with those with a healed index ulcer (p < 0.05) and by the end of the four-year period 61% of patients with unhealed, compared with 26% of those with healed index ulcers had had a recurrence. Patients over the age of 60 years with unhealed index ulcers had a significantly poorer prognosis than those of similar age whose index ulcer was healed at discharge (p < 0.025). The sex of the ulcer patient did not significantly influence ulcer recurrence. Large ulcers (> 57 mm(2)) were less often healed on initial discharge and were more frequently associated with recurrence at one (p < 0.05), two (p < 0.025), three and four years (p < 0.01) than smaller ulcers ([unk]57 mm(2)). Heavy intake of analgesics adversely influenced the course of patients whose ulcer was unhealed (p < 0.05), but did not alter the recurrence rate in those whose ulcer was healed. Ulcer recurrence was not influenced by smoking habits or by alcohol consumption.

Age Factors↗
PubMed1978

Chronic gastric ulcer and stress. A comparison of an ulcer population with a control population regarding stressful events over a lifetime.

Stress was measured by the frequency of 31 major life events with consequent change and distress scores in 50 patients with chronic gastric ulcer and 50 control subjects, matched for age, sex and place of residence. The gastric ulcer population did not differ from the control population regarding the number of events experienced and the associated change and distress scores. However, when analysed according to social grade, the ulcer patients in the lower status suburbs experienced more events and more change than their controls, but the stress scores were similar. In the higher status suburbs, no difference was present between the patients and controls. Change and distress scores rose progressively with age, but there was no significant difference in the number of events experienced between the three age groups. Both men patients and their controls experienced significantly more events and higher change scores than women patients and their controls.

Adult↗
PubMed1978

The identification of eight hydroxylated metabolites of etidocaine by chemical ionization mass spectrometry.

1. Eight hydroxylated metabolites of etidocaine have been identified in urine of man by g.l.c.-chemical ionization mass spectrometry, using methane and a mixture of methane and deuterium oxide as reactant gases. 2. The metabolites identified were N-(2,6-dimethyl-3- and 4-hydroxyphenyl-)-2-(N,N-ethylpropylamino)butyramides, N-(2,6-dimethyl-3- and 4-hydroxyphenyl)-2-aminobutyramides, N-(2,6-dimethyl-3- and 4-hydroxyphenyl)-2-(N-ethylamino)butyramides, and N-(2,6-dimethyl-3- and 4-hydroxyphenyl)-2-(N-propylamino)butyramides. 3. The eight metabolites represent about 10% of the oral dose of etidocaine.

Acetanilides↗
PubMed1978

Admitting by computer.

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Admitting Department, Hospital↗