Biomedical subjects
Publications and source records attributed to B Clarke.
The change in heart rate following infusion of adenosine in healthy human subjects was studied on two occasions. Adenosine produced a significant, dose-related increase in heart rate. Tachyphylaxis to this effect of the naturally occurring nucleoside did not occur. There was a tendency for prolonged infusion to cause a greater increase in heart rate, but this did not reach significance.
We have studied the cardiovascular effects of inhaled adenosine in healthy subjects. Adenosine at a concentration of 5 mg.ml-1 is absorbed and produces an increase in heart rate of 6-7 beats per min, blood pressure and skin temperature being unaltered. The rise in heart rate is less than that seen with an infusion of a comparable dose and is unlikely to be adequate for therapeutic termination of supraventricular tachycardia. Higher doses are limited by the poor solubility of adenosine. Inhalation as a method of delivering adenosine has possibilities as an alternative route of administration, but some practical problems remain to be overcome.
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Streptozotocin (STZ) diabetes was induced in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Body weight, blood pressure, renal function, glycaemic control and proteinuria were assessed monthly for 32 weeks. At 32 weeks, the animals were killed and glomerular basement membrane (GBM) thickness and fractional mesangial volume were measured. There was no significant difference in renal function between diabetic SHR and diabetic WKY. Diabetic SHR showed an earlier and larger rise in total proteinuria and urinary albumin excretion than diabetic WKY. Urinary albumin excretion was increased more than tenfold in diabetic SHR compared to diabetic WKY after 32 weeks of diabetes. GBM thickness was significantly increased in diabetic SHR compared with diabetic WKY. Both diabetic WKY and diabetic SHR showed mesangial expansion when compared to their nondiabetic counterparts. On the other hand, both hypertensive models showed increased glomerular volume, which was not influenced by the presence of diabetes. The diabetic SHR model has features of accelerated nephropathy, as evidenced by increased albuminuria and GBM thickness. This suggests that pre-existing hypertension may play an important role in the progression of diabetic renal disease.
The airway and cardiovascular effects of intravenous neurokinin A (NKA) and substance P (SP) were compared in six normal subjects. Both SP and NKA increased skin temperature (SkT) and heart rate (HR), but SP was more potent than NKA by factors of 6 and 20 respectively. No change in systolic blood pressure (BP) occurred with either peptide, but diastolic BP fell significantly with SP infusion. SP caused bronchodilation and NKA bronchoconstriction. NKA and SP have differing physiological roles and may activate different receptor populations.
Adenosine (0.05-0.25 mg/kg intravenously) successfully terminated resistant supraventricular tachycardia (SVT) in three seriously ill newborn infants and one older child. Termination of tachycardia was achieved in each case within 20 s. Adenosine, unlike many other anti-arrhythmic agents, has no substantial negative inotropic effect under these circumstances and may become the drug of choice in haemodynamically compromised children with SVT. However, it has no value in prophylaxis against recurrent SVT.
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It is not easy to see a simple outline in the progress of the idea of duality, because it did not develop evenly or reach the stage of general acceptance. From the seventeenth century there were shifts in some of the basic assumptions about how the brain and mind functioned, and there are some useful markers along the way to an era of more systematic studies. Descartes is the most convenient base. He had earlier firmly separated mind and matter in his philosophy, and is still chiefly known for that. But at the end of his life (1649) he tried to reconcile them by the device of a specific 'seat of the soul' in the brain through which information passed between brain and mind. Symmetry of the operation of the hemispheres was assumed. This theory had currency into the eighteenth century. At the end of that century Franz Gall of Austria and France was assigning discrete faculties to numerous parts of the brain on no strong evidence, and nothing the double form of the brain, without claiming independent action of the hemispheres. Hewett Watson in 1836 discussed duality more directly than had been the case before, and Arthur Wigan in 1844 asserted the duality of the mind roundly and treated the two hemispheres, not consistently, as two independent brains. He was not satisfied with independence, however, and tried various ways of allowing for joint action by the two sides of the brain, as well as for substitution, with one side having the power to act on behalf of both in cases of disease or injury. He also considered that one hemisphere, usually the left, was generally dominant; but he did not see the two hemispheres as differently constituted. Recognition of differentiation of function between the two sides came chiefly out of the largely French discussions, in the 1820s and after, about the location--frontal or not--of 'language', and out of the work and arguments of the middle of the century. Broca's left frontal language centre became widely known, though its experimental base was weak and he himself seems to have been more interested in the fact that it was frontal (the older debate) than in its one-sidedness. Brown-Séquard did not accept Broca's findings because of his general opposition to specific locations for particular functions; but he enthusiastically revived Wigan's notions of duality, without developing them further.(ABSTRACT TRUNCATED AT 400 WORDS)
In a single blind randomized study, eight normal subjects (23-40 years) received on two separate days adenosine as a constant i.v. infusion with doses increasing from 0.005-0.1 mg kg-1 min-1 following either i.v. dipyridamole 0.4 mg kg-1 per 10 min or a corresponding volume of saline. Heart rate, blood pressure and skin temperature were measured. Following saline all subjects tolerated adenosine 0.07 mg kg-1 min-1, six also tolerated 0.09 mg kg-1 min-1. Both heart rate and skin temperature increased with adenosine in a dose-related manner. Thus, adenosine 0.09 mg kg-1 min-1 was associated with an increase in heart rate (mean +/- SD) from baseline before saline with 16 +/- 10 b.p.m. (P less than 0.01) and an increase in skin temperature with 1.3 +/- 0.8 degrees C (P less than 0.02). Dipyridamole, which inhibits the cellular uptake of adenosine was associated with a change in heart rate similar to that induced by adenosine. Furthermore, when adenosine was infused following dipyridamole the changes in heart rate and skin temperature were potentiated as compared with adenosine following saline. Thus, following dipyridamole an increase in heart rate with 15 b.p.m. above baseline was obtained with 0.005 mg kg-1 min-1 of adenosine as compared with 0.08-0.09 mg kg-1 min-1 of adenosine following saline. Blood pressure did not change in any of the studies. Exogenous adenosine in man has a dose-related positive chronotropic effect and a local dilatory effect in the skin microcirculation. Dipyridamole potentiates the cardiovascular effects of infused adenosine in man.
Six healthy subjects (two female) aged 23-40 years participated in a double-blind randomized cross-over study to investigate autonomic mechanisms involved in the chronotropic effect of adenosine in conscious man. Adenosine was infused in increasing doses following saline, propranolol (0.2 mg kg-1 body weight) or propranolol (0.2 mg kg-1 plus atropine (0.04 mg kg-1). Heart rate and blood pressure were measured supine, on standing and during a Valsalva manoeuvre. Plasma catecholamines were measured in the supine and standing positions. Following saline, adenosine (up to 120 micrograms kg-1 min-1) caused a dose-related increase in heart rate (mean +/- SD maximum increase 18 +/- 8 bpm; P less than 0.01). The change in heart rate with adenosine after propranolol (12 +/- 9 bpm; P less than 0.05) did not differ significantly from the corresponding change following saline but was abolished by propranolol plus atropine, which, in turn, was associated with a mean maximum decrease in heart rate of 5 +/- 3 bpm (P less than 0.01). The increase in heart rate during the initial 30 s on standing was augmented with adenosine compared with saline (16 +/- 5 bpm; P less than 0.01). A significant increase in plasma noradrenaline on standing was also found with adenosine compared with saline (6.37 +/- 2.86 vs. 4.77 +/- 1.79 nmol 1(-1); P less than 0.05). The heart rate response to the Valsalva manoeuvre was not affected by adenosine. These results suggest that the positive chronotropic effect of infused adenosine in conscious man may in part be caused by an inhibition of cardiac vagal tone.(ABSTRACT TRUNCATED AT 250 WORDS)
In a study of 33 commercial abalone divers from the Port Lincoln area of South Australia nervous system function was examined using a battery of neurobehavioural tests. Their performance was compared with that of non-diver controls matched for age, sex, education level, job type, language abilities, and cigarette and alcohol consumption. Abalone divers showed significantly poorer vision, learning, and short term memory performance and increased tremor relative to their controls. The reaction time of abalone divers, however, was as fast as or significantly faster than that of controls but their error rates were much higher, indicating that abalone divers were sacrificing speed for accuracy. Despite their apparent risk taking approach to these tests, the performance of abalone divers suggests some impairment of nervous system function.
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Carcinoids are solid tumours arising from enterochromaffin cells, usually of the gastrointestinal or respiratory tract. They are fairly common, and in autopsy series have been present in up to 1% of cases. In contrast the carcinoid syndrome--the combination of flushing, diarrhoea, wheezing and heart disease due to release of vasoactive substances from these tumours--is rare. One estimate is that in a population of 250 000 over 10 years only two new cases would arise (Linell and Mansson, 1966).
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A patient with sinuatrial disease and implanted pacemaker was treated with amiodarone (maximum dose 1000 mg, maintenance dose 800 mg daily) for 10 months, for control of supraventricular tachyarrhythmias. He developed pneumonitis, pleural and pericardial effusions, and a predominantly proximal motor neuropathy. Immediate but gradual improvement followed withdrawal of amiodarone and treatment with prednisolone. Review of this and previously reported cases indicates the need for early diagnosis of amiodarone pneumonitis, immediate withdrawal of amiodarone, and prompt but continued steroid therapy to ensure full recovery.
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