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Biomedical subjects

R Hopkins

Publications and source records attributed to R Hopkins.

At least 127 records · Page 7Linked to original sources

Relationship between plasma concentrations and pharmacological effects of labetalol.

In healthy normal subjects following the administration of labetalol the pharmacological effects were measured and compared with the plasma concentrations achieved. The inhibition of exercise induced tachycardia and inhibition of exercise induced increases in systolic pressure were significantly related to the administered dose of labetalol. Labetalol was rapidly absorbed from the gastrointestinal tract and peak plasma concentrations occurred two hours after oral administration. There was a linear correlation (r = 0.84) between the logarithm of the plasma concentration and the maximum inhibition of exercise tachycardia at two hours. After intravenous administration there was an immediate reduction in systolic and diastolic blood pressure with a concomitant small increase in heart rate. There was a rapid decline in the associated plasma concentration but the pharmacological effects were maintained in excess of two hours. Our findings are consistent with those of others who have studied the relationship between pharmacological events and plasma concentrations after single doses of other adrenoceptor blocking drugs.

Administration, Oral↗

2-Aminopurine-induced mutagenesis in T4 bacteriophage: a model relating mutation frequency to 2-aminopurine incorporation in DNA.

We measured the in vivo incorporation of 2-aminopurine into DNA of T4 bacteriophage allelic for gene 43 (DNA polymerase), mutator (L56), 43+, and antimutator (L141). The magnitude of incorporation (mol/mol of Thy) was 1/1500 in L56, 1/1600 in 43+, and 1/8900 in L141. The incorporation ratio L56:43+:L141 in vivo was equal to that mediated by the purified DNA polymerases of these allelic phages in vitro. A model for 2-aminopurine-induced A-T in equilibrium G-C transitions is discussed. The model is used to predict the magnitudes of replication errors (C mispairing with a template 2-aminopurine) and incorporation errors (2-aminopurine mispairing with a template C) per round of replication and to investigate the asymmetry in 2-aminopurine-induced transitions favoring the A-T leads to G-C pathway over G-C leads to A-T. We suggest that the fidelity of L56 and L141 DNA polymerases exemplifies one-step and two-step editing, respectively.

2-Aminopurine↗

Communicating with the rheumatic patient.

To explore the meanings attached to words by patients and doctors, a multiple-choice questionnaire was given to 214 rheumatic patients, 110 non-rheumatic patients, 227 rheumatologists and 36 general practitioners. Words and phrases dealt with symptoms in descriptive terms, common disorders and parts of the body relevant to rheumatology. Poor agreement was obtained for 'back' among rheumatologists and hospital doctors, and for 'arthritis' among general practitioners. The word 'sciatica' means very different things to different doctors. Among rheumatic sufferers good agreement was only reached for 'rheumatism' and 'hereditary'. Non-rheumatic sufferers obtained better agreement than the rheumatic patients. This may have been due to more in the professional classes among the former group. The poorest agreement among rheumatic patients was for 'numbness', 'sciatica', 'slipped disc', 'vertebra', 'cervical', 'spinal cord', 'arthritis', 'deformity', 'anaemia', 'ligaments', 'osteoarthritis', 'lumbar', 'sacrum' and 'back'. Poor doctor-patient correlation between patients and rheumatologists occurred for 'numbness', 'spinal cord', 'cervical', 'sacrum', 'loin', 'slipped disc', 'arthritis', 'osteoarthritis' and 'steroids'.

Adult↗

Congenital tuberculosis.

Congenital tuberculosis is a rare and often fatal disease. This report concerned a premature infant in whom the disease was found after postpartum diagnosis in the mother. Use of endotracheal tube aspirates to diagnose tuberculosis in the infant is a unique feature of this case.

Adult↗

Administration of antirheumatic drugs.

A study of 200 rheumatic patients attending an outpatient clinic and 72 general practitioners (GPs) was undertaken in relation to the administration of antirheumatic drugs. (1) Both patients and GPs agreed that effectiveness, absence of toxicity, and once daily administration were the important features of administration. (2) Significant differences between GPs and patients were noted in that patients more frequently preferred capsules than tablets. (3) GPs thought red was the best colour for an antirheumatic tablet, whereas patients thought white, this opinion being partly determined by the possible confusion of red tablets with sweets by children. (4) In a survey of 174 outpatients with rheumatic diseases, those with rheumatoid arthritis did not like blister packaging. A detailed assessment of 30 patients with rheumatoid arthritis in hospital confirmed this. Patients with moderate or severe rheumatoid disease of the hands often could not extract tablets from blister packs. Those who could found the packs difficult to open, the tablets broke, and came out suddenly, falling to the floor.

Anti-Inflammatory Agents, Non-Steroidal↗

Metabolism of labetalol by animals and man.

1 The disposition and metabolism of labetalol and either 14C- or 3H-labetalol has been studied in mouse, rat, rabbit, dog and man. 2 Radiolabelled labetalol was administered orally at doses of 100 mg/kg to the mouse, up to 50 mg/kg to the rat and rabbit, 20 mg/kg to the dog and 200 mg to man. From measurements of the total plasma radioactivity it was shown that labetalol was well absorbed by all the species. When the measurements of plasma radioactivity and labetalol concentrations were compared, it was found labetaol had been extensively metabolized by the first-pass effect in rat, rabbit and man. Metabolism by this route occurred to a lesser extent in the dog. 3 Radiochemical analysis of the tissues from rats, rabbits and dogs showed that the highest concentrations of radioactivity were found in the lung, liver and kidney. Very little radioactivity was present in the brain. Over 99% of the radioactivity was cleared from the tissues by 7 d. When doses of up to 200 mg 14C-labetalol/kg were given to pregnant rats and 50 mg 14C-labetalol/kg to pregnant rabbits, autoradiographic and radiochemical analysis of the full-term foetuses showed that only small amounts of radioactivity were present in the foetus. 4 The mouse excreted 72%, the rate 48%, the rabbit 61%, the dog 66% and man 60% of the oral dose of radioactivity in the urine. Analysis of themouse and rat faeces showed that the remainder of the dose of radioactivity was excreted in the faeces. 5 Radiochemical analysis of the urine and faeces collected from rats and dogs after an intravenous dose of 1 mg 14C- and 3H-labetalol/kg showed that excretion of radioactivity occurred via both the kidney and bile. 6 An intravenous dose of 1 mg 3H-labetalol/kg to dog and 1 mg 'cold' labetalol/kg to man was not as extensively metabolized as a similar oral dose. 7 The percentage of the dose excreted in the urine as unchanged drug was 2% in the rabbit, 11% in the rat, 19% in the dog and up to 5% in man. The O-phenyl glucuronide was the major metabolite present in the mouse, rat, and rabbit urine. Dog and man also formed this metabolite, but to a lesser extent. A second glucuronide was the major metabolite present in dog urine. This was probably formed through conjugation of glucuronic acid was the secondary alcohol group of labetalol. The major metabolite present in human urine was an unidentified conjugate of labetalol. Minor metabolites of labetalol present in rat, rabbit and dog urine were hydroxylabetalol and its glucuronyl conjugate.

Administration, Oral↗

Detection of hepatitis B surface antigen among Scottish blood donors: evaluation of sensitive tanned-cell haemagglutination-inhibition test.

A total of 70 224 blood donations were tested at three Scottish blood transfusion centres for hepatitis B surface antigen /HBsAg) by an economical haemagglutination-inhibition method (E.H.A.I.) and the results compared with those of counterelectrophoresis (C.E.P.). A further 4086 donations were tested using the Wellcome turkey cell haemagglutination test, C.E.P., and E.H.A.I.E.H.A.I. was also compared with commercial haemagglutination and radioimmunoassay reagents for sensitivity and specificity against several established antigen panels and used to reinvestigate counterelectrophoresis-negative blood donations implicated in post-transfusion hepatitis. E.H.A.I. combines the inherent specificity of an inhibition reaction with a sensitivity equal to that of commercial radioimmunoassay and haemagglutination kits but at a fraction of the cost. The assessment of 70 224 blood donations in three regions showed that E.H.A.I. detected more antigen-positive blood donations than C.E.P. Results of retesting more than 100 blood donors implicated in 10 cases of post-transfusion hepatitis suggested that the use of E.H.A.I. or a test of similar sensitivity in place of C.E.P. may significantly reduce the incidence of this complication.

Antibody Specificity↗

ad and ay subtypes of hepatitis B antigen in a case of hypogammaglobulinaemia.

We describe the finding of d and y specificities of hepatitis B surface antigen (HBsAg) in a case of hypogammaglobulinaemia of the 'common variable' type treated with fresh frozen plasma infusions. Absorption studies show that the two specificities are on separate particles, suggesting dual infection. It raises important questions regarding the relationship between HBsAg persistence and the immune status of the carrier.

Agammaglobulinemia↗