Biomedical subjects
Publications and source records attributed to D F Muir.
A case is presented of recurrent stent thrombosis unexplained by angiographic appearance, which subsequently revealed a diagnosis of antiphospholipid syndrome secondary to renal cell carcinoma.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
5-Hydroxytryptamine (5-HT; serotonin) has been implicated in the perception of exercise-induced fatigue. Sumatriptan is a selective 5-HT(1B/D) receptor agonist which does not cross the blood-brain barrier. The aim of the present study was to determine the effect of sumatriptan on exercise capacity. Ten healthy male subjects (mean age 28.4+/-10.8 years) performed a maximal treadmill exercise test according to the Bruce protocol with expired gas analysis on two occasions. Either 6 mg of sumatriptan or placebo was administered subcutaneously in a randomized, double-blind, placebo-controlled, cross-over design. Exercise time was greater after placebo compared with sumatriptan [914 and 879 s respectively; 95% confidence interval (CI) of difference 12.1 s, 59.1 s; P = 0.008]. There was no significant effect on peak oxygen consumption (placebo, 50.6+/-6.3 ml.min(-1).kg(-1); sumatriptan, 51.7+/-7.6 ml.min(-1).kg(-1)). Sumatriptan administration resulted in decreases in both heart rate (sumatriptan, 188+/-14 beats/min, placebo, 196+/-12 beats/min; 95% CI of difference 12.6, 2.6; P = 0.008) and respiratory exchange ratio (sumatriptan, 1.23+/-0.06; placebo, 1.26+/-0.07; 95% CI of difference 0.05, 0.01; P = 0.01) at peak exercise. There were no significant differences in blood pressure, heart rate or submaximal oxygen consumption between sumatriptan and placebo treatments at any stage of exercise. Thus sumatriptan reduces maximal exercise capacity in normal males. The failure to demonstrate any haemodynamic or cardiorespiratory effect suggests that sumatriptan enhances perception of fatigue by a peripheral mechanism affecting 5-HT modulation.
BACKGROUND: We evaluated the prevalence of left ventricular hypertrophy in elite footballers compared with sedentary controls. A total of 141 elite male professional footballers and 32 healthy sedentary controls were studied. Echocardiographic and demographic variables were compared between groups by unpaired t-test. RESULTS: The prevalence of left ventricular hypertrophy with maximal wall thickness values out with the normal range (>12 mm) was noted. Footballers were significantly younger than controls (20.9 vs. 24.3 years, P<0.005: 95% CI (-5.2, -1.73)) but there were no significant differences in height, weight or body surface area between the groups. Each of inter-ventricular septum (10.4 vs. 9.1 mm, P<0.0001; 95% CI (0.88, 1.72)), posterior wall (9.2 vs. 8.5 mm, P<0.01; 95% CI (0.22, 1.21)), left ventricular cavity (systolic and diastolic) (34.5 vs. 28.4 mm, P<0.0001; 95% CI (4.31, 7.76) in systole; 50.1 vs. 48.2 mm, P<0.05; 95% CI (0.15, 3.74) in diastole), aortic root size (29.1 vs. 27.8 mm, P<0.05; 95% CI (0.03,2.49)) and left ventricular mass index (112 vs. 89 g/m2, P<0.0001; 95% CI (14.4, 32.1)) were significantly greater in footballers than in controls. Absolute left ventricular wall thickness >12 mm was present in 17 footballers (12%) (range 13-15 mm) and in no controls. CONCLUSIONS: Elite professional footballers have increased cardiac dimensions compared with healthy controls. The prevalence of absolute wall thicknesses out with the normal range is relatively high.
OBJECTIVE: To investigate the systemic, pulmonary, and coronary artery effects of eletriptan, a new 5HT1B/1D-agonist in patients undergoing cardiac catheterization. METHODS: Ten patients (two men and eight women) without significant obstructive coronary artery disease were administered 3.33 microg/kg/min intravenous eletriptan after they were given a placebo infusion of 0.9% saline solution. Serial measurements of right heart and systemic pressures were taken at 5-minute intervals during placebo infusion, eletriptan infusion, and a 30-minute postinfusion period. Cardiac output by the thermodilution technique and coronary angiography were performed every 15 minutes. Quantitative coronary angiography was carried out to measure coronary artery dimensions. RESULTS: A small but statistically significant increase in occluded wedge pressure (7.4 versus 8.8 mm Hg; 95% confidence interval [CI], 0.74, 2.51; P < .01), right atrial pressure (5.3 versus 6.1 mm Hg; 95% CI, 0.0, 1.4; P < .05), and mean pulmonary artery pressure (13.2 versus 14.6 mm Hg; 95% CI, 0.0, 2.7; P = .05) was observed during the eletriptan infusion compared with placebo. A statistically significant increase in systemic vascular resistance (1256 versus 1519 dyne/sec/cm(-5); 95% CI, 126, 398; P < .01) and pulmonary vascular resistance (76.4 versus 100.8 dyne/sec/cm(-5); 95% CI, 1.9, 46.9; P < .05) was observed in the period after drug infusion. No overall effect was observed on the coronary arteries, although a segmental right coronary artery constriction developed in one patient, possibly as a result of catheter-induced spasm. CONCLUSIONS: Eletriptan, a 5HT1B/1D-agonist effective in migraine, causes no significant coronary artery constriction in patients without significant obstructive coronary artery disease. This finding may reflect a relative selectivity for the 5HT1D-receptor subtype.
AIMS: To investigate the effects of an intravenous infusion of BMS-180048, a novel 5HT1-like agonist, on the systemic, pulmonary and coronary circulations in patients undergoing diagnostic cardiac catheterisation. METHODS: Ten patients (mean age 55 years (range 41-65)) were studied during diagnostic cardiac catheterisation. The haemodynamic response to an intravenous (i.v.) infusion for 30 min of BMS-180048 (0.56 mg kg(-1) h(-1) for 10 min and 0.39 mg kg(-1) h(-1) for 20 min) was assessed via a 7F Swan Ganz catheter and thermodilution cardiac output system. Quantitative coronary angiography was performed at 10 min intervals. RESULTS: BMS-180048 caused a significant increase in systemic arterial systolic blood pressure (rise of 32.5 mmHg, 95% CI 24,44.5) P=0.009), pulmonary artery systolic (12.2 mmHg, 95% CI 6.8,18.5; P=0.009) and diastolic pressures (8.5 mmHg, 95% CI 5.0,13.8; P=0.009), right atrial pressure (4 mmHg, 95% CI 1.5,5.2; P=0.013) and pulmonary capillary wedge pressure (9.5 mmHg 95% CI 5.2,14.0; P=0.09). There was no significant change in cardiac output (0.1 l min(-1), 95% CI -0.17,0.57, P>0.05). Mean coronary artery diameter in the proximal coronary segments decreased by 0.73 mm (95% CI -1.22,-0.15; P=0.03) at 35 min. The corresponding reduction in middle segments was 0.26 mm (95% CI -0.395,-0.08; P=0.02). There was a non-significant trend to constriction in the most distal segments of 0.28 mm (95% CI -0.68,0.015); P=0.06). One patient experienced chest pain with ECG changes suggestive of ischaemia. CONCLUSIONS: BMS-180048 displayed a cardiovascular profile similar to that previously reported for sumatriptan. These changes appear to reflect a class effect of these agents.
A randomized prospective trial was undertaken to compare the hemodynamic performance and left ventricular regression after aortic valve replacement with the Toronto SPV stentless bioprosthesis and the Carpentier Edwards SAV (CE) bioprosthesis. Forty patients were randomized after the annular and sinotubular diameters had been measured. Early hemodynamic measurements were made with a thermodilution cardiac output catheter, and echocardiography was used thereafter. Left ventricular mass was assessed using magnetic resonance imaging (MRI) at 1 week, 6 months, and 32 months. The mean annular size was 25.3+/-2.2 mm (CE) and 25.5+/-1.5 mm (Toronto), although it was possible to implant valves with a mean diameter 3 mm larger in the stentless group (26.0+/-1.7 mm cf. 23.0+/-1.7 mm). Hemodynamic performance in the first 24 hours showed no significant difference between the groups, but there was a trend for shorter ventilation time and shorter stays in the intensive therapy unit in the stentless group. Echocardiography showed superior transvalvular gradients in the stentless group at 1 week (mean 5.5+/-3.1 mm Hg cf. 8.9+/-2.5 mm Hg), and this difference was maintained at a mean follow-up time of 32 months (3.5+/-0.6 mm Hg cf. 6.3+/-0.6 mm Hg). Similar regression of left ventricular mass was seen in both groups at 6 months, but at 32 months, measurement in diastole showed a reduction of 38% (P<.01) in the stentless group compared with 20% (P = ns) in the stented group, and measurements in systole showed a 23% (P<.01) and 13% (P = ns) reduction, respectively. This study confirms that a larger stentless valve can be implanted into a given size of aortic annulus with superior residual aortic valve gradients. These lower gradients seem to result in improved long-term regression of left ventricular mass as measured by MRI.
Tumor development and progression in the nervous system are poorly understood. Consequently, even though there seems to be little possibility of major advances in existing clinical modalities used to treat malignant brain tumors, no targeted molecular therapies have risen to take their place. The variability and plasticity of brain neoplasms make them an illusive target for study and therapeutic intervention. Further complicated by infiltration of vital nervous tissue, clinical studies have serious practical limitations and the ability to assess tumor progression in vivo is still a developing technology. Evaluation of potential new therapies for brain tumors is heavily dependent on the development of more informative and cognate experimental models. To develop and validate new models, it is particularly important to integrate clinical, pathological, and cell biological characterizations of malignant brain tumors. This discussion provides an overview of developments in tumor cell culture and the impact of animal models on brain tumor research. Studies of malignant glial neoplasms associated with a dismal prognosis in patients receive particular attention.
Scanty irregular opacities are not uncommonly observed on the chest roentgenogram in the absence of interstitial fibrosis of the lungs. In such circumstances the irregular opacities, when present, tend to be relatively scanty and seldom, if ever, exceed an ILO category of 1/1. They are found in association with cigarette smoking, especially when emphysema is also present. The development of irregular opacities is also related to exposure to various mineral and other dusts, and although their prevalence increases with cumulative dust exposure, in general the type of dust, whether fibrogenic or relatively inert, seems to be of little moment. The presence of irregular opacities remains a troublesome confounding factor in epidemiologic studies of both dust-exposed and nonexposed populations. The morbid anatomic changes that occur in the lungs of nondust-exposed workers and which are responsible for the development of irregular opacities in the chest roentgenogram remain unknown.
1. In a retrospective study, we stratified 79 patients with paracetamol hepatotoxicity into two groups according to weekly alcohol consumption below (n = 49) or above (n = 30) Royal College of Physicians' guidelines of 21 units week-1 for males and 14 for females. 2. Survival was lower (33%) and serum creatinine on admission higher (median 207 mumol) in patients whose alcohol consumption was above recommended guidelines than in those whose drank less than this (65.9% and 138 mumol, P less than 0.01 and P = 0.027, respectively). An arterial blood pH less than 7.30 on admission was also more common in those patients with a higher alcohol consumption (30% v 12.2%, P = 0.05). 3. In all patients whose alcohol consumption exceeded the guidelines, paracetamol overdose was fatal if associated with a serum creatinine greater than 300 mumol in conjunction with a prothrombin time over 100 s and grade 3 or 4 encephalopathy or a peak prothrombin time over 180 s. 4. Chronic alcohol intake above suggested limits is an adverse prognostic feature in cases of severe paracetamol overdose. This effect is partly related to increased nephrotoxicity.