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Biomedical subjects

M Riley

Publications and source records attributed to M Riley.

At least 73 records · Page 4Linked to original sources

Respiratory gas exchange and metabolic responses during exercise in McArdle's disease.

During normal progressive exercise, the gas exchange anaerobic threshold occurs when CO2 production (VCO2) and ventilation (VE) increase so as to depart from a linear relationship to O2 consumption (VO2). This is thought to represent a gas exchange response to metabolic acidosis due to lactate accumulation. Patients with McArdle's disease have previously been reported to exhibit a steepened ventilatory response relative to VCO2, despite an inability to produce lactate. However, the VCO2 response has not been studied. We therefore investigated the VCO2-VO2 and VE-VO2 relationships in seven McArdle's disease patients and seven control subjects during symptom-limited maximal treadmill exercise. Analysis of gas exchange showed that whereas all control subjects had an easily identifiable anaerobic threshold, four of the patients had none and the other three displayed an attenuated threshold. The occurrence of the threshold in one patient was associated with a small rise in lactate and in another patient with an abrupt rise in leg discomfort, suggesting a pain response. Ammonia and the purine metabolite hypoxanthine were elevated during exercise in all patients, suggesting that ammonia may be a product of adenosine monophosphate degradation. Free fatty acid levels were also elevated, and a shift toward utilization of lipid may contribute to abnormal gas exchange responses. It is concluded that lactic acidosis contributes to the gas exchange anaerobic threshold but that other factors, such as discomfort, may be involved in the excess Ve seen during heavy exercise.

Adolescent↗

Representations of metabolic knowledge.

Construction of electronic repositories of metabolic information is an increasingly active area of research. Encoding detailed knowledge of a complex biological domain requires finely honed representations. We survey representations used for several metabolic databases, including Eco-Cyc, and reach the following conclusions. Representation of the metabolism must distinguish enzyme classes from individual enzymes, because there is not a one-to-one mapping from enzymes to the reactions they catalyze. Individual enzymes must be represented explicitly as proteins, e.g., by encoding their subunit structure. The species variation of metabolism must be represented. So must the substrate specificity of enzymes, which may be treated in several ways.

Databases, Factual↗

Effect of beta-adrenoceptor blockade on atrial natriuretic peptide levels during exercise in angina pectoris.

The effects of epanolol (200 mg once daily) and diltiazem (60 mg three times daily) on the response of atrial natriuretic peptide (ANP) to exercise were investigated in a double-blind placebo-controlled crossover study in 16 patients with angina pectoris. Exercise tolerance as assessed by peak oxygen consumption was similar with all treatments. Peak heart rate (mean and 95% confidence intervals) was lower (P < 0.05) with epanolol (121 (115-130) beats min-1) than with diltiazem (137 (126-148) beats min-1) or placebo (141 (130-152) beats min-1). ANP did not change from resting values with placebo or diltiazem, but rose significantly (P < 0.05) with epanolol from 19.7 (13.0-29.8) pg ml-1 (geometric mean and 95% confidence intervals) during supine rest to 49.6 (33.7-73.0) pg ml-1 at peak exercise. Since ANP release is stimulated by atrial distension, patients with untreated angina may stop exercise before atrial dilatation occurs. With beta-adrenoceptor blockade, a reduction in peak heart rate may necessitate increased chamber volumes to maintain cardiac output, accounting for the rise in ANP.

Adrenergic beta-Antagonists↗

Role of plasminogen-activator inhibitor type 1 in the pathogenesis and outcome of the hemolytic uremic syndrome.

BACKGROUND: Deposition of fibrin in glomeruli and renal failure are characteristic features of the hemolytic uremic syndrome. An inhibitor of glomerular fibrinolysis has been detected in plasma from children with this disorder. In this study, we define the inhibitor and show that its plasma level is correlated with the outcome of the disease. METHODS AND RESULTS: Plasminogen-activator inhibitor type 1 (PAI-1) in plasma was measured with an assay employing a specific monoclonal antibody in 40 consecutive children hospitalized with the hemolytic uremic syndrome: 12 who recovered adequate renal function (serum creatinine, less than or equal to 2.0 mg per deciliter [177 mumol per liter]) without dialysis, 23 who recovered adequate renal function after peritoneal dialysis, and 5 who did not recover adequate renal function after undergoing dialysis. At presentation, plasma PAI-1 levels were higher in the patients with the hemolytic uremic syndrome than in nine children with other forms of acute renal failure. That the inhibitor was PAI-1 was indicated by the fact that it was a potent inhibitor of tissue plasminogen activator, was acid-resistant, and was not inhibited by denaturation (all unique traits of PAI-1) and that it was neutralized by an antibody specific for PAI-1. Multivariate discriminant-function analysis revealed that the duration of elevated PAI-1 activity was strongly correlated with the outcome of the disease (P less than 0.001). Peritoneal dialysis reduced plasma PAI-1 levels dramatically. CONCLUSIONS: Our studies suggest that PAI-1 is the circulating inhibitor of fibrinolysis in the hemolytic uremic syndrome. Normalization of plasma PAI-1 levels (e.g., by peritoneal dialysis) is correlated with improvement in renal function. However, the possibility that increased plasma levels of PAI-1 are either causes or effects of the hemolytic uremic syndrome is not unequivocally established by these studies.

Acute Kidney Injury↗

The use of an exponential protocol for bicycle and treadmill exercise testing in patients with chronic cardiac failure.

We have studied a standardized exercise protocol suitable for use with a treadmill or bicycle (STEEP protocol) and compared it with a modified Bruce treadmill protocol in a group of patients with chronic cardiac failure. The STEEP protocol has been previously validated in normal subjects. Exercise time (6.79 +/- 2.42 vs 5.34 +/- 1.95 min, P < 0.05) and peak VO2 (16.66 +/- 4.09 vs 15.01 +/- 3.72 ml.min-1.kg-1, P < 0.05) were greater with the STEEP treadmill compared with the bicycle protocol, but VO2 was very similar at equal exercise stages in both modalities. Heart rate and respiratory exchange ratio tended to be greater during bicycle exercise at equal stages. Exercise time was greater with the modified Bruce protocol (9.00 +/- 3.02 min, P < 0.05) than with either STEEP protocol, but peak VO2 (17.13 +/- 4.52 ml.min-1.kg-1) was similar to that obtained with the STEEP treadmill test. We conclude that the STEEP protocol may be used to test patients with chronic cardiac failure, and that exercise times relate well in both treadmill and bicycle. The protocol should prove useful in studies involving a wide range of exercise capacities or both bicycle and treadmill exercise.

Aged↗

Regulatory peptides in the plasma of patients with chronic cardiac failure at rest and during exercise.

The levels of several regulatory peptides were measured in peripheral plasma samples from individuals with chronic cardiac failure (CCF) and matched controls in both the resting state and during a short period of maximal exercise. Basal levels of noradrenaline (NA; 705 +/- 114 vs 195 +/- 54 ng.l-1; mean +/- SEM; P < 0.05), plasma renin activity (PRA; 12.9 +/- 2.9 vs 2.1 +/- 0.3 ng AI ml-1.h-1; P < 0.05) and aldosterone (ALDO; 325 +/- 49 vs 87 +/- 8 ng.l-1; P < 0.05) were all raised in the patients with CCF, and increased further with exercise. Basal circulating levels of atrial natriuretic peptide (ANP) were also significantly higher in the CCF group compared to controls (136 +/- 35 vs 27 +/- 5 ng.l-1; P < 0.01), but the response to exercise was attenuated, so that at peak exercise, no significant difference was observed. Basal circulating levels of gastrin-releasing peptide (GRP) (29 +/- 4 vs 40 +/- 4 ng.l-1; P < 0.05) and secretin (13 +/- 1 vs 32 +/- 4 ng.l-1; P < 0.05) were significantly lower in the CCF group when compared to controls and there was no significant change in the levels of either peptide with exercise. Levels of neurokinin A (NKA), neuropeptide Y (NPY) and neurotensin (NT) were somewhat higher in patients, but the differences were not significant, and there were no changes during exercise. There were also no significant differences in the levels of vasoactive intestinal peptide (VIP), glucose-dependent insulinotropic polypeptide (GIP), insulin or glucagon in either experimental group both before and during exercise. We have therefore identified different circulating levels of certain regulatory peptides in patients with CCF, but the significance of these remains unclear.

Adult↗

Oxygen consumption during corridor walk testing in chronic cardiac failure.

We have examined the use of a 6-min corridor walk test in the assessment of functional capacity in 16 patients with chronic cardiac failure. VO2 was determined concurrently by a portable 'Oxylog'. Three tests were performed sequentially, and although there was a significant increase in distance walked and highest VO2 achieved between the first and second tests, good reproducibility was attained between the second and third tests. Both walk test variables correlated well with previously determined peak achieved VO2, and NYHA classes were separated adequately. Corridor walk testing, with or without measurement of VO2 should be a useful adjunct to maximal exercise testing in interventional studies.

Aged↗

Comparative effects of epanolol and diltiazem on exercise performance and respiratory gas exchange in angina pectoris.

The effects of epanolol (a new selective beta-adrenoceptor antagonist), diltiazem and placebo were compared in a group of 16 patients with chronic stable angina pectoris. Each patient received each treatment in random order. Diltiazem reduced weekly angina attack rate from 7.2 (95% CI 3.9-10.5) to 3.9 (1.9-5.9) (P less than 0.01), whereas a lesser reduction was observed after epanolol. Both drugs produced a small but significant (P less than 0.05) increase in treadmill exercise time (placebo 474 s (374-574), epanolol 527 s (431-623) and diltiazem 554 s (462-646). However, aerobic work capacity, assessed by peak achieved oxygen consumption, was not different from the placebo value of 21.2 (18.0-24.4) ml.min-1.kg-1, and clearly subnormal when compared to age- and sex-matched controls (33.0 (30.1-35.9) ml.min-1.kg-1). Ventilatory abnormalities and increased lactate levels on active treatment were observed at peak exercise only. We conclude that the cardiodepressant effects of both active drugs limit blood supply to working skeletal muscle, and that chest pain may be replaced by dyspnoea or fatigue as the limiting factors to exercise.

Adrenergic beta-Antagonists↗

The Work Environment Scale: a comparison of British and North American nurses.

Previous research into stress in nursing has identified different sources of stress for different specialties without specifying the source of that stress or providing comprehensive understanding of the variables that might contribute to it. This study examines the work environment of 209 nursing staff using the Work Environment Scale. Significant differences were found between a UK sample and the original American norms. Further research highlighted significant interactional effects between demographic variables and the subscales of the WES, and these may form the basis for future research.

Analysis of Variance↗

Bone abnormalities and severe arthritis in pachydermoperiostosis.

Two patients with pachydermoperiostosis were studied in whom the predominant features at presentation were severe and disabling knee and ankle joint pain in association with distal long bone pain. Analysis of synovial fluid from the knee joints showed non-inflammatory changes. In one patient a bicortical iliac crest bone biopsy specimen, taken after labelling with demeclocycline, showed appositional rates which were increased in cortical bone but reduced in trabecular bone. This mismatching resulted in trabecular osteoporosis, which occurred in association with increased numbers of osteoclasts, findings which suggest differential functional changes affecting the two bony envelopes.

Adolescent↗

Effect of caffeinated coffee on running speed, respiratory factors, blood lactate and perceived exertion during 1500-m treadmill running.

Using a motorized treadmill the study investigated the effects of the ingestion of 3 g of caffeinated coffee on: the time taken to run 1500 m; the selected speed with which athletes completed a 1-min 'finishing burst' at the end of a high-intensity run; and respiratory factors, perceived exertion and blood lactate levels during a high intensity 1500-m run. In all testing protocols decaffeinated coffee (3 g) was used as a placebo and a double-blind experimental design was used throughout. The participants in the study were middle distance athletes of club, county and national standard. The results showed that ingestion of caffeinated coffee: decreases the time taken to run 1500 m (P less than 0.005); increases the speed of the 'finishing burst' (P less than 0.005); and increases VO2 during the high-intensity 1500-m run (P less than 0.025). The study concluded that under these laboratory conditions, the ingestion of caffeinated coffee could enhance the performance of sustained high-intensity exercise.

Adolescent↗

Delayed onset of cardiac arrhythmias from sustained-release verapamil.

Sustained-release products in overdose are known to produce prolonged effects as well as delayed onset. The availability of sustained-release calcium channel blockers may produce an initial misleading picture for patients who are at risk for serious toxicity. We report the cases of two adults who had delayed onset of arrhythmias after ingestion of sustained-release verapamil. In both cases, a single dose of activated charcoal was administered, but the patients still developed toxicity. Some of the unique problems encountered with sustained-release formulations are discussed, and 24-hour cardiac monitoring for sustained-release calcium channel blocker overdoses, despite a possible early asymptomatic period, is suggested.

Adult↗

Resting energy expenditure in chronic cardiac failure.

1. Resting energy expenditure has previously been shown to be elevated in the acute phase of heart failure, but the situation in the compensated state of chronic cardiac failure is unclear. Resting energy expenditure was assessed in 14 patients with stable chronic cardiac failure and 14 matched control subjects by using indirect calorimetry. 2. Resting energy expenditure was significantly elevated in the patients with chronic cardiac failure (112.6 +/- 18.1 versus 87.1 +/- 12.2 kJ day-1 kg-1 total body weight, P less than 0.0002; mean +/- SD) as were resting O2 consumption (3.88 +/- 0.64 versus 3.00 +/- 0.43 ml min-1 kg-1, P less than 0.0002), ventilation (164 +/- 40.3 versus 104 +/- 16.2 ml min-1 kg-1, P less than 0.0001) and heart rate (85.8 +/- 16.9 versus 66.6 +/- 6.9 beats/min, P less than 0.001). Both the resting plasma concentration of noradrenaline (4.48 +/- 1.52 versus 2.28 +/- 0.96 nmol/l, P less than 0.0001) and the serum concentration of free fatty acids (0.78 +/- 0.21 versus 0.57 +/- 0.27 mmol/l, P less than 0.03) were greater in the patients with chronic cardiac failure. Analysis of covariance indicated that most of the difference in resting energy expenditure could be accounted for by the elevated ventilation in the patients with chronic cardiac failure. Arm muscle area, an index of wasting, was lower in the patients with chronic cardiac failure (39.1 +/- 13.1 versus 50.5 +/- 9.4 cm2, P less than 0.02) and resting energy expenditure was found to account for some of this difference. 3. We conclude that an elevated basal metabolism occurs in chronic cardiac failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Transcutaneous oxygen tension in the leg during exercise in patients with chronic cardiac failure.

The transcutaneous partial pressure of oxygen measured in the lower limb was compared in 16 patients with chronic cardiac failure and seven normal subjects. At rest, there was no significant difference between patients and normals. At peak exercise, the partial pressure of oxygen fell significantly in those in heart failure, whereas no change was observed in normal subjects. No changes in arterial oxygen saturation (oximetry) were observed. These changes are likely to reflect abnormalities of peripheral perfusion of the skin.

Blood Gas Monitoring, Transcutaneous↗