Prospects for teaching hospitals.
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Biomedical subjects
Publications and source records attributed to J Chalmers.
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The effects of sinoaortic denervation on arterial blood pressure and central activity of phenylethanolamine-N-methyl transferase (PNMT, the last enzyme in adrenaline biosynthesis), were compared in normotensive Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHR-SP). Denervation of the arterial baroreceptors caused immediate increases in mean arterial blood pressure (MAP) in all three strains which were maximal at 90 min (32 mmHg in WKY, 51 mmHg in SHR and 80 mmHg in SHR-SP). Spinal cord PNMT activity increased above sham-operated levels in WKY at 90 min, but PNMT levels in SHR and SHR-SP, already significantly higher than in WKY, were not altered acutely after sinoaortic denervation. Over a seven day period after baroreceptor denervation, MAP rose by 15 mmHg in WKY and PNMT activity was about 100% greater in spinal cord and ventral medulla. In the two genetically hypertensive strains sinoaortic denervation failed to produce a further sustained rise in pressure or and PNMT activity in the ventral medulla or spinal cord. We suggest that increased activity of bulbospinal adrenaline neurons contribute to the sustained elevation in pressure seen in intact SHR and SHR-SP, as well as in WKY after denervation of arterial baroreceptors.
Two cases of aneurysmal bone cyst in the pelvis which healed spontaneously are described. Spontaneous regression of aneurysmal bone cysts has not previously been well documented. Our experience with these two cases suggests that radical intervention is not always necessary.
We have studied the mechanisms contributing to the characteristic cardiovascular response produced after lesions of the A1 noradrenaline cell area in the ventrolateral medulla of the rabbit, at and below the level of the obex. Forty-five minutes after the A1 lesions there were dramatic increases in plasma adrenaline and plasma vasopressin (AVP) levels, which rose more than forty-fold, accompanied by smaller increases in plasma noradrenaline concentration and plasma renin activity (PRA) which were approximately doubled. Administration of an AVP antagonist did not effect the pressor response to A1 lesions but did reduce the bradycardia whereas administration of phentolamine, an alpha adrenoceptor blocker, completely prevented the increase in blood pressure after lesions. Administration of propranolol and methylscopolamine together, reduced the magnitude of the bradycardia by blocking cardiac efferent mechanisms mediating baroreceptor reflexes, but left a persistent residual fall in heart rate which was independent of baroreflexes; on the other hand when the AVP antagonist was given simultaneously with propranolol and methylscopolamine the bradycardia was completely abolished. Furthermore, infusion of AVP producing plasma levels similar to those seen after A1 lesions, caused a fall in heart rate and cardiac output with only a minor degree of vasoconstriction and no change in mean arterial pressure. An inhibitor of angiotensin converting enzyme had no effect on either heart rate or blood pressure. The rise in blood pressure observed after lesions of the A1 noradrenaline cell region is principally due to activation of the sympatho-adrenal system. The bradycardia is partly reflex due to stimulation of arterial baroreceptors. There is a marked rise in plasma AVP which exerts a minor vasoconstrictor effect but contributes directly and more substantially to the fall in heart rate.
Lesions of the ventrolateral medulla coinciding with the A1 noradrenaline cell group, in either the rabbit or the rat, cause hypertension and bradycardia accompanied by 50-fold increases in plasma vasopressin and adrenaline and a two-to-four-fold increase in plasma noradrenaline. Following adrenalectomy in normal rats, the A1 hypertension and bradycardia were unchanged. In Brattleboro rats with diabetes insipidus, A1 hypertension was not altered but the bradycardia was reduced by 40%. In Brattleboro rats subjected to adrenalectomy, the hypertension was reduced by 50%. In normal rats, chemical sympathectomy with intravenous 6-hydroxydopamine (6OHDA) reduced the hypertension by about 50%, and when combined with adrenalectomy it abolished the hypertension altogether. In Brattleboro rats, 6OHDA reduced the hypertension after A1 lesions by about 40%. We suggest that A1 hypertension is predominantly mediated through increased activity of sympathetic vasoconstrictor nerves, and that circulating adrenaline and vasopressin only make a minor contribution to the increase in pressure.
A purification scheme is described for the neutral glutathione S-transferases of rat liver. Discontinuous sodium dodecyl sulphate/polyacrylamide-gel electrophoresis revealed that one of these enzymes contains a previously unidentified subunit, which has a molecular mass of 23 000 Da and has been designated Yn. Bile acids inhibited the activity of all the basic and neutral transferases investigated, but marked differences in the effects of bile acids on individual enzymes were observed. The activity of each transferase was inhibited more by lithocholate 3-sulphate than by chenodeoxycholate, which in turn was more inhibitory than cholate. The enzymes that were most sensitive to cholate inhibition were not found to be as readily inhibited as other transferases by chenodeoxycholate or lithocholate 3-sulphate. Conversely, the activity of transferase AA was more resistant to cholate, chenodeoxycholate and lithocholate 3-sulphate inhibition than was any of the other enzymes studied.
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One hundred and sixteen patients with proven bronchiectasis diagnosed at least five years previously were studied to determine the clinical outcome, change in pulmonary function, and degree of social disability. Twenty-two patients had died and the mean duration of follow-up in the survivors was 14 years. The patients who died were characterised by a poorer initial ventilatory capacity than the survivors and cor pulmonale was present in 37% at the time of death. The survivors showed a tendency for improvement in symptoms whether treated surgically or medically. Thirty per cent were better than at diagnosis while only 11% were worse. Measurements of FEV1 and FVC were made at diagnosis and at review, mild airways obstruction being the predominant abnormality. The change in pulmonary function was expressed as the decline in FEV1 in ml/yr. The decline in FEV1 was no greater than expected in 80% of patients and in a further 15% was of the order seen in cigarette smokers with mild airways obstruction. Poor ventilatory capacity was therefore not an important limitation in these patients. Of the survivors 77% had a good work record with less than two weeks loss of work annually from chest illness. The spouses of all married patients were interviewed at home by a trained social worker. Fifty per cent reported no social problem but 46% of spouses found the patient's cough distasteful and 29% of couples had experienced difficulties with normal sexual life. Seven per cent of the patients were severely disabled. While the overall prognosis of our patients was good a minority still have severe physical and social problems as a result of bronchiectasis.
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In 30 elderly women awaiting hip arthroplasty on account of unilateral osteoarthritis of the hip, walking speed and oxygen consumption were measured during a 12-minute test and the power output was calculated from the stair climbing rate. The results were compared with those for a group of 30 normal women of similar age. An age-related decline in maximal walking speed was observed in both groups. After arthroplasty there was a significant increase in maximal walking speed, particularly among the more disabled patients, with the major gain occurring by three months and a further slight increase by six months. Oxygen consumption returned towards normal values, and both stride length and cadence increased by a comparable degree. Mean power output during stair climbing doubled, and both before and after arthroplasty bore a linear relationship to the maximal walking speed.
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The effects of timolol (10 mg thrice daily) and hydrochlorothiazide (50 mg/day) have been compared in a double-blind factorial trial in 20 patients with essential hypertension. There were four randomised test phases of 8 weeks each during which patients received timolol alone, hydrochlorothiazide alone, timolol plus hydrochlorothiazide, and no treatment (placebo). Blood-pressure was measured weekly, alternately at the outpatient clinic and at the patient's home. Supine mean arterial pressure fell from 119 mm Hg in the placebo phase to 110 mm Hg in the hydrochlorothiazide phase, 106 mm Hg in the timolol phase, and 101 mm Hg in the combined timolol plus hydrochlorothiazide phase. Factorial analysis revealed that these effects of the two drugs were additive without any potentiation or antagonism. Mean plasma-renin activity (P.R.A.) was 5-02 ng/ml/3 h in the placebo phase falling to 1-79 in the timolol phase and rising to 9-54 in the diuretic phase, but remaining unchanged in the combined treatment phase (5-40 ng/ml/3 h). The data suggest that the hypotensive action of timolol is not dependent on the concomitant fall in P.R.A. The methods described provide a valuable tool for quantitating the effects of a given drug, and hence a valid basis for objective comparison.
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