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Biomedical subjects

J Thomas

Publications and source records attributed to J Thomas.

At least 703 records · Page 39Linked to original sources

Pharmacokinetics of zimelidine in humans--plasma levels and urinary excretion of zimelidine and norzimelidine after intravenous and oral administration of zimelidine.

Five healthy adults were administered zimelidine orally (150 mg) and by intravenous infusion (20 mg) in a crossover design. Blood and urine samples were collected for a period of 28 hours after dosing and the concentrations of zimelidine and norzimelidine determined. There was no significant difference in terminal phase half-life of zimelidine after oral (4.7 h +/- 1.3 SD) or intravenous dosing (5.1 h +/- 0.7 SD). An average of 50% of the ingested oral dose reached the systemic circulation. Excretion of unchanged zimelidine in urine was on average 1.26% of the intravenous dose. It appears that zimelidine is completely absorbed from the gastrointestinal tract and "first-pass metabolism" in the liver reduces the bioavailability to 50%. The mean plasma half-life for norzimelidine was 22.8 h. The area under the plasma concentration time curve for norzimelidine after oral administration was 92% of that after intravenous administration. The plasma concentration of both zimelidine and norzimelidine are predicted to approach steady-state within 3--5 days.

Administration, Oral↗

Respiratory obstruction caused by a multicentric granular cell tumor of the laryngotracheobronchial tree.

An unusual case of acute respiratory obstruction caused by multicentric granular cell tumors of the laryngotracheobronchial tree is presented. The patient also had granular cell tumors in the tongue, vulva, and chest wall. Multiplicity of the lesions in the left lung and recurrent episodes of intercurrent pulmonary infections necessitated left pneumonectomy. The extreme rarity of such a clinical circumstance is illustrated by a review of the literature. Salient clinical and pathological features of the tumor are briefly discussed.

Adult↗

Cytokinin-induced wall extensibility in excised cotyledons of radish and cucumber.

The mechanism of cytokinin-induced cell expansion in cotyledons excised from dark-grown seedlings of radish (Raphanus sativus L.) and cucumber (Cucumus sativus L.) was studied. Cotyledons were incubated in dim light with or without 17 micromolar zeatin for periods up to 3 days. Fresh weights and osmotic potentials were measured daily. Cell wall extensibility properties were measured before and after the growth period. Also, experiments in which radish cotyledons were grown in mannitol solutions of various concentrations were performed. Comparisons of growth rates and increases of tissue osmotic potentials (toward zero) during growth without mannitol indicate that wall extensibility increased during the growth period and that this extensibility was enhanced by zeatin.Extensibility values derived from growth rates in mannitol provided indirect evidence of zeatin-increased wall extensibility. These conclusions were verified by direct measurements of plasticity with an Instron extensiometer. Thus, growth stimulation of excised cotyledons by cytokinins apparently involves wall loosening, in addition to previously demonstrated increases of K(+) absorption and formation of reducing sugars.

Journal Article↗

Indapamide in the treatment of essential arterial hypertension in the elderly.

Twenty-four patients (average age 72 years) took part in a study of the effectiveness and tolerance of indapamide as medication for essential hypertension in elderly subjects. 2.5 mg was administered daily for two months, after which the same amount was given once every other day in order to investigate whether the antihypertensive effect would persist at this dosage. After two months treatment with 1 tablet of indapamide 2.5 mg daily, statistically significant (P less than 0.01) drops in the mean systolic and diastolic blood pressures both erect and supine were observed. In 18 of the patients, the results obtained underwent no statistically significant modifications during the second 2-month treatment period at reduced dosage. In 5 others, dosage had to be maintained at 1 tablet daily. In all cases, the drug was well tolerated clinically. ECG recordings were unchanged. Laboratory results remained within the normal range despite a slight increase in serum uric acid and a slight decrease in potassium.

Aged↗

Histology of the Fernandez reaction. An appraisal.

The early lepromin reaction was studied clinically and histologically in 38 leprosy patients. There was a quantitative and a qualitative difference in the character of the early inflammatory response to lepromin in the different groups of leprosy patients. In tuberculoid patients, the extent and degree of inflammation and the density of lymphocytic infiltration were maximal. In the polar lepromatous group, the inflammatory reaction was far less intense, and lymphocytes were scarce or absent. An intermediate histology was noted in the borderline and indeterminate groups of patients. In 11 patients with negative clinical reactions, the histology showed moderately dense lymphocytic infiltrations. The paucity of the clinical reaction could be due to the injection and localization of the antigen in the mid- and deep dermis. The correlation between early and late lepromin reactivity, both clinically and histologically, in the polar tuberculoid group and the polar lepromatous group was good. In the borderline and indeterminate groups, only the correlation between the early and late histological reactions to lepromin was good. The relationships between the early and late clinical reactions to lepromin showed marked variation. It is suggested that the early reaction is as good an indicator of lepromin reactivity as the late reaction in all forms of leprosy but only if it is assessed histologically.

Adolescent↗

Factors influencing palmitoyl-CoA oxidation by rat liver peroxisomal fractions. Substrate concentration, organelle integrity and ATP.

1. The first dehydrogenation step of peroxisomal beta-oxidation involves the reduction of O2 to H2O2. Production rates of H2O2 and acetyl units by purified rat liver peroxisomes oxidizing palmitoyl-CoA were equal, indicating that H2O2 production is a reliable index for the release of acetyl units during peroxisomal fatty-acid oxidation. 2. Measurements of H2O2 and acid-soluble oxidation products during [1-14C]palmitoyl-CoA oxidation by purified peroxisomes revealed that the number of acetyl units released per molecule of palmitoyl-CoA oxidized rapidly decreased with increasing unbound palmitoyl-CoA concentrations. Structural damage to the peroxisomes caused by detergents or other treatments also decreased the number of acetyl units released. Under conditions where oxidation proceeded linearly with time the theoretical maximum of 5 acetyl units released per molecule of palmitoyl-CoA oxidized [Lazarow (1978) J. Biol. Chem. 253, 1522--1528] was never reached. 3. Expressed in terms of acetyl units produced and measured at low unbound-palmitoyl-CoA concentrations, mitochondrial oxidation was 10--20-fold higher than peroxisomal oxidation. 4. ATP stimulated peroxisomal palmitoyl-CoA oxidation approx. 2-fold. The ATP effect required the presence of Mg2+ and was lost when peroxisomal membranes were disrupted by Triton X-100 or high concentrations of unbound palmitoyl-CoA. 5. Disruption of peroxisomes by detergents, freeze--thawing, osmotic or mechanical treatment did not stimulate palmitoyl-CoA oxidation in the presence of ATP, indicating that peroxisomal fatty-acid-CoA oxidation was not latent. In the absence of ATP, Triton X-100 stimulated peroxisomal palmitoyl-CoA oxidation approx. 2-fold.

Acyl Coenzyme A↗

Regulation of glutamine synthetase in the blue-green alga Anabaena L-31.

In N2-grown cultures of Anabaena L-31, in which protein synthesis was prevented by chloramphenicol, presence of NH+4 caused a drastic decrease of glutamine synthetase (L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2) activity indicating NH+4-mediated inactivation or degradation of the enzyme. The half-life of glutamine synthetase was more than 24 h, whereas that of nitrogenase (reduced ferredoxin:dinitrogen oxidoreductase (ATP-hydrolysing), EC 1.18.2.1) was less than 4 h, suggesting that glutamine synthetase may not act as positive regulator of nitrogenase synthesis in Anabaena. Glutamine synthetase purified to homogeneity was subject to cumulative inhibition by alanine, serine and glycine. The amino acids, however, exhibited partial antagonism in this behaviour. Glyoxylate, an intermediate in photorespiration, virtually prevented the amino acid inhibition. Kinetic studies revealed inhibition of the enzyme activity by high Mg2+ concentration under limiting glutamate level and by high glutamate in limiting Mg2+. Maximum enzyme activity occurred when the ratio of glutamate to free Mg2+ was 0.5 to 1.0. The results demonstrate that the enzyme is subject to multiple regulation by various metabolites involved in nitrogen assimilation.

Amino Acids↗

Quantitation of doxapram in blood, plasma and urine.

Methods for the quantitation of doxapram in blood, plasma and urine have been developed. Following extraction, gas-liquid chromatography was used to separate doxapram from basic metabolites. Doxapram was detected by mass spectrometry for blood and plasma assays, and by flame ionisation for urine assays. The limit of reliable quantitation in blood and plasma was 10 ng and in urine 500 ng, the coefficients of variation being 6.37%, 1.72% and 2.31% respectively. To illustrate the clinical applicability of the assay methods, plasma, blood and urine levels were monitored in a premature newborn following an intravenous infusion of doxapram.

Apnea↗