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Biomedical subjects

J Wadsworth

Publications and source records attributed to J Wadsworth.

At least 19 recordsLinked to original sources
PubMed1979

Relationship between bronchial effects and plasma practolol concentration in man.

A double-blind, balanced and randomised study in 8 healthy volunteers examined the effects of relatively high versus low single doses of practolol on heart rate and ventilation at rest and during standardised exercise. Practolol 1 and 4 mg/kg, a typically non-selective drug propranolol 0.2 mg/kg, and placebo were given intravenously at weekly intervals. Cardiac beta-adrenoceptor blockade was measured by the reduction in exercise heart rate greater than 160 beats/min, and bronchial beta-adrenoceptor blockade by the reduction in exercise peak expiratory flow rate (PEFR) up to 4 h after each treatment. Results were assessed by analysis of co-variance. All three active treatments reduced exercise heart rate markedly, practolol 4 mg/kg causing most reduction. Exercise PEFR was significantly reduced by propranolol 0.2 mg/kg compared with both practolol 1 mg/kg and placebo at all times of measurement, and by practolol 4 mg/kg compared with practolol 1 mg/kg and placebo at most times. Mean plasma concentrations after practolol 4 mg/kg were 3.5 to 4.5 times higher than after 1 mg/kg. Practolol may lose its 'cardioselectivity' and cause airflow obstruction at relatively high plasma concentrations above about 2 microgram/ml.

Adult↗
PubMed1979

Comparison of four weeks' treatment with fenoterol and terbutaline aerosols in adult asthmatics. A double-blind crossover study.

Fenoterol and terbutaline, two long-acting beta 2-adrenoceptor agonists in aerosol form, were compared in an 8-wk randomized double-blind crossover study in 22 mild to moderately severe asthmatics. Patients completed diary cards, recorded peak expiratory flow rate (PEFR) twice daily, and attended a clinic for measurement of PEFR, 1-sec forced expiratory volume (FEV1), and forced vital capacity (FVC) twice during each treatment period. Fifteen patients completed the study; 5 dropped out while using fenoterol, and 2 while using terbutaline. At clinic attendances, the patients had a significantly higher mean PEFR after 4 wk on terbutaline (385 L/min) than after fenoterol (316 L/min) (p less than 0.001). Similar results were found on analysis of the morning and evening PEFR recordings. On comparing each individual's PEFR recordings during the 2 treatments, it was found that there was no significant difference among the treatments in 3 patients, while 9 patients had a better response to terbutaline, and 3 patients had a better response to fenoterol. While similar number expressed a subjective preference for each treatment, the lung function data suggested that the effectiveness of fenoterol appeared to decline during the trial period.

Adult↗
PubMed1979

Predicting phenytoin dose - a revised nomogram.

The nomogram devised by Richens and Dunlop for predicting phenytoin dose has been tested in 127 residential epileptic patients, and the data obtained were used to prepare a revised version of the nomogram. In a further 78 patients, this new version was found to be superior to the original. The mean Km value was found to be 23.8 mumoles/liter. Km was independent of age and body surface area, but Dmax correlated positively with the latter two variables.

Adolescent↗
PubMed1979

The effect of spontaneous changes in urinary pH on mexiletine plasma concentrations and excretion during chronic administration to healthy volunteers.

1. The effect of spontaneous changes in urinary pH on renal excretion and plasma concentration of mexiletine has been examined during chronic administration of subtherapeutic doses of the drug to healthy volunteers. 2. Significant correlations were found between urinary pH and the plasma concentration and renal excretion of mexiletine. 3. Prediction of plasma mexiletine concentrations from our data suggests that the amount of mexiletine in plasma would increase by more than 50% following a rise in urinary pH similar to that which occurred spontaneously in our subjects. 4. Factors which influence urinary pH should be considered when the dosage of mexiletine is chosen. Extremes of urinary pH may account for some cases of inefficacy of the drug, and for the occurrence of unwanted effects at conventional doses.

Adult↗
PubMed1979

Clinical staging in multiple myeloma.

Analysis of 237 patients with myeloma, retrospectively classified according to the staging system proposed by Durie and Salmon, showed highly significant differences (P less than 0.0001) in the survival of patients with low, intermediate and high tumour cell masses (Stages I, II and III respectively). The median survival for Stage I patients was 64 months, Stage II 32 months, and Stage III 6 months. The median survival of patients presenting with renal impairment was only 2 months, compared to 21 months for those presenting with normal renal function (P less than 0.0001). The use of this clinical staging system, which is based on myeloma protein synthesis rates and the calculation of total body tumour cell mass, should be considered in planning future trials of therapy in this disease.

Female↗
PubMed1979

Measurement of serum proteins during attacks of ulcerative colitis as a guide to patient management.

Serial measurements of 11 serum proteins have been made throughout 39 admissions of 36 patients to hospital for the treatment of acute attacks of ulcerative colitis. There was a striking correlation between rapid changes in C-reactive protein and pre-albumin concentrations and the clinical response to medical treatment. Measurements of the alpha1-acid glycoprotein, albumin, and total serum protein concentrations at the time of admission were found to correlate with the outcome of the attack. Measurement of these proteins provides a useful guide to the management of patients with attacks of ulcerative colitis.

Adult↗
PubMed1979

Cardiovascular effects of amitriptyline, mianserin, zimelidine and nomifensine in depressed patients.

The cardiac effects of amitriptyline, mianserin, zimelidine and nomifensine on the systolic time intervals (STI) and on the high speed surface ECG have been studied in depressed patients. Amitriptyline increased pre-ejection period (PEP) index and the PEP/left ventricular ejection time (LVET) ratio of the STI (P less than 0.05 and P less than 0.02). It also increased heart rate significantly (less than 0.02) and tended to prolong Q-T interval. Mianserin shortened QS2I (P less than 0.05) and LVET (P less than 0.01) and prolonged PEP/LVET ratio (P less than 0.01). Zimelidine did not affect the STI but tended to decrease heart rate and prolong the Q-T interval. Nomifensine decreased T wave height. These findings indicate that amitriptyline decreases cardiac contractility and confirm the quinidine-like action of the tricyclic antidepressants. The changes brought about by mianserin are probably due to effects on the peripheral circulation rather than a direct action on the heart.

Adult↗
PubMed1979

Clinical pharmacological studies of amoxycillin: effect of probenecid.

In a study of eight, healthy adult volunteers given 3 g amoxycillin with or without 1g probenecid, significantly higher peak plasma levels of amoxycilin were recorded in the presence (34.96 microgram/ml) of probenecid than in its absence (22.72 microgram/ml). When plasma levels were plotted against time the mean area under the curve was significantly greater for subjects given probenecid than for those given amoxycillin alone. These findings suggest that 3g amoxycillin plus 1g probenecid provide better bioavailability than 3g amoxycillin alone. The plasma levels obtained were several times higher than the minimun inhibitory concentrations (MICs) of most strains of gonococci. Plasma levels in excess of the MICs for most strains were maintained for eight hours with both regimens, but the higher levels in the presence of probenecid support the better clinical results previously reported with this regimen.

Adult↗
PubMed1979

How often are gonorrhoea and genital yeast infection sexually transmitted?

Although gonorrhoea is often regarded as the sexually transmitted disease against which others are measured, its infectivity is not clearly understood. Estimates of the infection rate have varied from 5--90%. In this study, 50 couples with gonorrhoea were matched with 50 couples with genital yeast infection. Gonorrhoea was diagnosed in both partners of 32 couples and genital yeast infection in both partners of 21 couples. These figures provide an indication of the sexual transmission of these conditions. The higher figure for gonorrhoea may be related to a greater urgency in tracing contacts.

Adolescent↗
PubMed1978

Primary suture of the perineal wound following rectal excision for inflammatory bowel disease.

Delay in healing of the perineal wound is a major cause of disability in patients after excision of the rectum. The outcome of primary suture in 76 patients treated at St Mark's Hospital between 1967 and 1976 was correlated with a number of factors describing the patients, their preparation for surgery and details of surgical technique and management. The perineal wound healed by first intention in 33 patients. The remaining 43 patients regarded as failures included 7 with delayed breakdown after initial healing. The results showed that women fared better than men. Excision of the rectum following colectomy and ileostomy was associated with failure of the perineal wound to heal in 9 out of 10 patients. Treatments with peroperative ampicillin and topical antibacterial agents were both correlated significantly with success. Preoperative sepsis and operative contamination were followed by perineal sepsis and wound breakdown on 16 out of 21 occasions. Discriminant analysis showed that topical and peroperative antibacterial treatments, sex, preoperative sepsis and finally ACTH were the most important variables in descending order of importance. The prediction of success and failure by this procedure was 72.4 per cent correct.

Adult↗
PubMed1978

Plasma protein binding interaction between phenytoin and valproic acid in vitro.

1 Valproic acid or phenytoin were added to fresh human serum in varying concentrations and their binding characteristics determined by the method of Scatchard (1949). 2 Changes in serum albumin binding were investigated for phenytoin in the presence of 280, 560, 1050 and 2100 mumol l-1 valproic acid, and for valproic acid in the presence of 40, 120, 280 and 480 mumol l-1 phenytoin. 3 Phenytoin appeared to bind to a single site on the albumin molecule and could be competitively displaced from this site by concentrations of valproic acid above 280 mumol l-1. 4 At high concentrations of valproic acid, the affinity of phenytoin for albumin was greatly decreased but the number of available binding sites was increased from one to four. 5 Valproic acid was bound to two high affinity and five low affinity binding sites but the latter were not detectable at valproic acid concentrations below 2100 mumol l-1. 6 Phenytoin displaced valproic acid from its high affinity binding sites, although this was statistically significant only at a concentration of 480 mumol l-1 phenytoin.

Binding Sites↗
PubMed1978

Studies of cardioselectivity and partial agonist activity in beta-adrenoceptor blockade comparing effects on heart rate and peak expiratory flow rate during exercise.

1 The effects of beta-adrenoceptor antagonists given in single doses by oral or intravenous routes were examined in two double-blind controlled studies performed in healthy volunteers. Heart rate and peak expiratory flow rate (PEFR) were measured at rest and during standardized exercise. 2 Propranolol 80 mg and metoprolol 100 mg orally tended to reduce, and propranolol and metoprolol 0.2 mg/kg intravenously did reduce the physiological increase in PEFR during exercise; oxprenolol 80 mg orally and 0.2 mg/kg intravenously did not. Practolol 200 mg orally reduced this increase, but practolol 1 mg/kg intravenously did not. 3 In a third study of similar design, pindolol 0.05 mg/kg intravenously did not affect exercise-induced increase in PEFR. 4 Heart rate during exercise was reduced to a comparable extent at different times by all the active treatments. 5 Oxprenolol and pindolol share with practolol the property of partial agonist activity, which might contribute to their apparent lack of effect on airways resistance. A further possibility is that alpha-adrenoceptor blockade helps to maintain exercise-induced increase in PEFR.

Adrenergic beta-Antagonists↗