Biomedical subjects
Publications and source records attributed to D MacLeod.
There are only a few conflicting reports on the effects of moderate altitude on cognitive factors that could affect sporting performance. An investigation of choice reaction time in international rugby players at various altitudes was therefore carried out. The results suggest that moderate altitude has no significant effect on this parameter in highly trained competitive athletes.
Recent studies have suggested that theophylline, a nonspecific phospho-diesterase inhibitor, has useful anti-inflammatory actions in asthma. Phosphodiesterase 4 (PDE4) represents the predominant PDE isoenzyme present in inflammatory cells. PDE4 inhibitors might, therefore, have beneficial effects in asthma. Side-effects, specifically nausea, have limited the use of existing agents. CDP840 is an orally active, potent and selective PDE4 inhibitor. We have examined the effect of CDP840 on the allergen-induced asthmatic response, its possible modes of action, and its tolerability at therapeutic doses. A total of 54 patients were recruited to three double-blind, placebo-controlled studies. The first study examined the effect of CDP840 (15 mg b.i.d. for 9.5 days) on the allergen-induced asthmatic response in patients with known dual response to allergen. A second study examined the effect of CDP840 (15 mg b.i.d. for 9.5 days) on airway responsiveness to histamine. A third study examined whether single dose CDP840 (15 and 30 mg) had significant bronchodilatory effects. In all studies, CDP840 was well-tolerated, with no patients reporting nausea. CDP840 did not lead to changes in baseline forced expiratory volume in one second (FEV1) as compared to placebo. The late asthmatic response (LAR) to allergen, expressed as area under the curve at 3-8 h (AUC3-8h), was inhibited by 30% (p=0.016), an effect which persisted to the end of the observation period. The early asthmatic response (EAR) was unaffected, and there was no bronchodilatory effect at the doses used. Treatment with CDP840 did not affect bronchial hyperresponsiveness to histamine. In conclusion, CDP840 significantly attenuated the late asthmatic response to allergen challenge in the absence of any bronchodilatory or histamine antagonist effect. This suggests that CDP840 may exert its effects via an anti-inflammatory mechanism.
The aim of this study was to investigate the behaviour of parameters which can be obtained by a 7-component model of the lung using impulse oscillometry in calves. Seven healthy conscious calves were examined using "Master Screen IOS" (E. Jaeger GmbH & Co. KG, Würzburg/D) and the following study design: [I] baseline measurements, [II] measurements after inhalation saline, [III] measurements during carbachol-induced bronchoconstriction, [IV] measurements after bronchodilatation by fenoterol. Measurements were made individually using a rigid face mask. Examining the spectral behaviour of the respiratory impedance (5 to 35 Hz), reactance (X) was more sensitive to bronchochallenge (stages [all] and [IV]) than resistance (R). Using the 7-component model of the lung, the resistance was differentiated into a central part (Rz) and a peripheral part (Rp). Changes in Rp were more significant than changes in Rz during stages [III] and [IV]. The parameters central inertance (Lz), chest wall compliance (Cw), and lung compliance (Cl) did not change during the study. Surprisingly, the parameter called "bronchial compliance" (Cb) increased significantly during bronchoconstriction. Therefore, further research is necessary to clarify whether the model needs to be modified for general applications or only for measuring bovines.
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OBJECTIVE: To test the hypothesis that, with the wheels locked (by the mechanical locks or by the user grasping the wheels), the rear wheels and the chair rotate slowly backwards during a fall, whereas with the wheels unlocked, the rear wheels rotate quickly forwards. DESIGN: Before-after trial. SETTING: Kinesiologic laboratory. PARTICIPANTS: Ten nondisabled adults, a sample of convenience. INTERVENTION: In a single representative wheelchair, subjects were dropped from beyond their balance points onto a mat with the rear wheels locked (L), with two hands grasping the rear wheels (TH), and with the wheels unlocked (UL). MAIN OUTCOME MEASURES: From videorecordings, the horizontal displacement of the rear wheels, the rotation of the rear wheels, and the fall times were derived. Using an anthropomorphic test dummy (ATD) and a Kistler force platform, the impacts of the head with the floor were also recorded. RESULTS: In both the L and TH conditions, the rear wheels moved and rotated backwards. The UL condition was significantly different than the L and TH conditions, with the rear wheels moving and rotating forwards and the fall occurring more quickly, with mean differences of 442 and 455mm, 84.0 degrees and 87.1 degrees, and .52 and .45 sec (p < or = .0001). The forces on the ATD's occiput were 12,280 and 21,118N in the L and UL conditions, respectively, and lasted approximately 20msec. CONCLUSION: Locking or grasping the rear wheels has a profound effect on the nature of rear-tipping incidents, a finding with important implications for the training of users in how to fall safely.
Theophylline has traditionally been considered for its effect on airway calibre in the treatment of bronchial asthma. However, in this respect theophylline is less potent than the current highly selective beta-agonists. In view of the accumulated evidence of potent effects of this nonspecific phosphodiesterase inhibitor on several inflammatory cell types, there is increasing belief that the anti-inflammatory potential of theophylline may be central to its beneficial effects in the treatment of airways inflammatory diseases such as asthma. This is based on its ability to attenuate the late phase asthmatic response and to prevent an influx of eosinophils and T-cells both in the setting of experimental allergen challenge and in clinical disease.
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The clinical efficacy and safety of directional coronary atherectomy for the treatment of stable and unstable angina were assessed in 82 patients with stable and 68 patients with unstable angina. Therefore, clinical and angiographic follow-up was obtained in a prospectively collected consecutive series of 150 atherectomy procedures. Restenosis was assessed clinically and by quantitative angiography. The overall clinical success rate of atherectomy for patients with unstable and stable angina was 88% and 91%, respectively. No significant differences were found for in-hospital event rates between the unstable and stable angina groups: death (1.5% vs 0%), myocardial infarction (10% vs 6%), and emergency bypass operation (3% vs 2%). These clinical events were related to the occurrence of abrupt occlusions (8.8% in patients with stable and 6.1% in those with unstable angina; p = NS). Clinical follow-up was achieved in 100% of the patients with stable and unstable angina at a mean interval of 923 and 903 days, respectively. Two-year survival rates were 96% and 97% in the populations with unstable and stable angina, respectively. There were no significant differences with respect to bypass surgery and angioplasty, but event-free survival at 2 years was significantly lower in the unstable (54%) than the stable (69%) angina group. Quantitative coronary angiography did not detect any difference in luminal renarrowing during the 6-month angiographic follow-up period. Although directional coronary atherectomy can be performed effectively in patients with unstable and stable angina, the long-term clinical outcome was less favorable in the unstable angina group.(ABSTRACT TRUNCATED AT 250 WORDS)
The measurement of the complex respiratory impedance at a high temporal resolution is described. The measurement of impedance is correlated with the breathing cycle using electrical transthoracic impedance. This allows the determination of the complex impedance at any fixed point in the respiratory cycle, which results in lower variability in the measured data when compared to the original device. The respiratory impedance in normal subjects fluctuates during the breathing cycle and has two maxima during a single breath, which occur at peak inspiratory and expiratory flow. In addition, the measurement of impedance at a high temporal resolution enables the observation of novel features in the impedance which appear to be associated with certain respiratory disorders.
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To establish the cardiovascular profile of nicorandil in patients with coronary artery disease, we recently conducted three studies at our institution. In two groups of patients undergoing cardiac catheterization, the effects of 20 mg nicorandil sublingually (s.l.) on, first, left ventricular hemodynamics (n = 10) and, second, coronary vasodilatation (n = 11) were investigated. In the first group, despite a significant decrease of 12% in left ventricular systolic pressure, heart rate did not increase significantly after nicorandil. Both left ventricular end-diastolic pressure (-43%) and the time constant of early isovolumic relaxation (-11%) decreased, whereas peak Vce and Vmax increased (+19%) (all significantly). In the second group, as mean aortic pressure decreased (-13%, p < 0.05), coronary sinus blood flow did not change significantly, and calculated coronary vascular resistance tended to decrease (-10%). Myocardial oxygen consumption decreased significantly by 14%. Quantitative coronary angiography confirmed a significant increase in the mean diameter of nonstenotic coronary artery segments (+ 14%, n = 43) and, importantly, in mean obstruction diameter of stenotic segments (+ 14%, n = 7) after s.l. nicorandil. In a third continuing study, the effects of intracoronary (i.c.) nicorandil (6 micrograms/kg) and isosorbide dinitrate (2 mg) on the epicardial coronary arteries were investigated in 10 patients undergoing coronary angioplasty. In nonstenotic coronary artery segments, mean coronary diameter increased significantly after either nicorandil (+ 12%) or isosorbide dinitrate (+ 17%). In stenotic segments, however, where the increase in obstruction diameter (+ 20%) after i.c. nicorandil was significant, the 8% increase of isosorbide dinitrate was not.(ABSTRACT TRUNCATED AT 250 WORDS)
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The effects of DNA methylation on gene expression and chromatin structure suggest the existence of a mechanism in the nucleus capable of distinguishing methylated and non-methylated sequences. We report the finding of a nuclear protein in several vertebrate tissues and cell lines that binds preferentially to methylated DNA in vitro. Its lack of sequence-specific requirements makes it potentially capable of binding to any methylated sequence in mammalian nuclei. An in vivo counterpart of these results is that methylated CpGs are inaccessible to nucleases within nuclei. In contrast, non-methylated CpG sites, located mainly at CpG islands, and restriction sites not containing this dinucleotide, are relatively accessible. The possibility that DNA methylation acts through binding to specific proteins that could alter chromatin structure is discussed.
Eight patients who developed a ventricular septal defect after myocardial infarction were assessed by cross sectional echocardiography and pulsed wave Doppler scanning. Cross sectional echocardiography visualised the defect in four patients and gave an accurate assessment of global and regional left ventricular function in all eight. In all patients pulsed wave Doppler scanning detected turbulent flow at the apex of the right ventricle or adjacent to a wall motion abnormality affecting the interventricular septum. Pulsed wave Doppler detected coexisting mitral regurgitation in one patient and tricuspid regurgitation in another two. In all patients a left to right shunt was confirmed by oximetry and the location of the defect was identified by angiography or at operation or necropsy. Cross sectional echocardiography in combination with pulsed wave Doppler scanning is useful in the rapid bedside evaluation of patients with ventricular septal defect after myocardial infarction.
The new calcium antagonist felodipine has been compared with minoxidil in the management of severe hypertension in a group of 17 men. Satisfactory control of blood pressure was achieved in all patients with a combination of beta blocker, loop diuretic and minoxidil after inadequate control on a standard regimen of beta blocker, thiazide and vasodilator. The optimal dose of felodipine was titrated after a placebo phase. In a double blind crossover trial blood pressure on felodipine (150/88 +/- 19/8 mmHg, SD) was the same as on minoxidil (148/87 +/- 23/11 mmHg, NS) and the postural difference was similar (NS) on both drug regimens. Body weight was lower on the felodipine regimen (P less than 0.01), as was supine heart rate (P less than 0.05). There was a small rise in plasma liver enzymes on felodipine therapy (P less than 0.01). Felodipine was well tolerated and may be useful in the management of severe hypertension.
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In a group of 15 men with severe hypertension in a double-blind crossover trial, the new calcium antagonist felodipine has been shown to lower blood pressure as effectively as minoxidil when used in combination with a beta-blocker and a loop diuretic. Felodipine was well tolerated and may have a role in the management of severe hypertension.