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Biomedical subjects

J Conway

Publications and source records attributed to J Conway.

At least 19 recordsLinked to original sources

Pitfalls in the interpretation of spectral analysis of the heart rate variability during exercise in humans.

The recent use of spectral analysis of the R-R interval variability to assess the autonomic drive during exercise has produced inconsistent results. The purpose of this study was to assess whether the spectral components of the R-R interval variability reflect different mechanisms at rest and during exercise. Autoregressive spectral analysis of the electrocardiographic and breathing signals was performed in 11 healthy young men at rest and during incremental cycle ergometry. The amplitude of respiratory sinus arrhythmia, i.e. the absolute power of the high frequency spectral component, fell at the onset of exercise, consistent with a reduction in cardiac vagal activity. Conversely, the normalized power of the high frequency component, (i.e. the percentage of R-R interval variance due to the respiratory sinus arrhythmia) increased with increasing work rates. The low frequency spectral component of the R-R interval variability, which when expressed in normalized units is believed to reflect cardiac sympathetic activity, was no longer detectable in severe exercise when the adrenergic drive is known to be elevated. In conclusion, autoregressive spectral analysis of the R-R interval variability does not adequately reflect the autonomic changes that occur during incremental exercise. In particular, the evidence indicates that as the cardiac vagal tone falls with increasing levels of exercise, a greater percentage of the residual power of the high frequency component may be due to non-neural mechanisms.

Adult

Effect of physical training on exercise-induced hyperkalemia in chronic heart failure. Relation with ventilation and catecholamines.

BACKGROUND: The exercise-induced rise in arterial potassium concentration ([K+]a) may contribute to exercise hyperpnea and could play a role in exertional fatigue. This study was designed to determine whether the exercise-induced rise in [K+]a is altered in patients with chronic heart failure (CHF) and whether physical training affects K+ homeostasis. METHODS AND RESULTS: We evaluated 10 subjects with CHF (ejection fraction, 23 +/- 3.9%) and 10 subjects with normal left ventricular function (NLVF) who had undergone previous coronary artery graft surgery (ejection fraction, 63 +/- 8.6%). Subjects performed an incremental cycle ergometer exercise test before and after a physical training or detraining program. Changes in [K+]a and ventilation (VE) during exercise were closely related in both groups. Subjects with CHF did less absolute work and had reduced maximal oxygen consumption (VO2max) compared with subjects with NLVF (P < .01). Exercise-induced rises in [K+]a, VE, norepinephrine, lactate, and heart rate were greater at matched absolute work rates in subjects with CHF than in subjects with NLVF (P < .01). However, when the rise in [K+]a was plotted against percentage of VO2max to match for relative submaximal effort, there were no differences between the two groups. Physical training resulted in reduced exercise-induced hyperkalemia at matched submaximal work rates in both groups (P < .01) despite no associated change in the concentration of arterial catecholamines. At maximal exercise when trained, peak increases in [K+]a were unaltered, but peak concentrations of catecholamines were raised (P < .05). The decrease in VE at submaximal work rates after training was not significant with this incremental exercise protocol, but both groups had an increased peak VE when trained (P < .01). CONCLUSIONS: Exercise-induced rises in [K+]a, catecholamines, and VE are greater at submaximal work rates in subjects with CHF than in subjects with NLVF. Physical training reduces the exercise-induced rise in [K+]a but does not significantly decrease VE during submaximal exercise with this incremental cycle ergometry protocol. The reduction in exercise-induced hyperkalemia after training is not the result of altered concentrations of arterial catecholamines. The pathophysiological significance of the increased exercise-induced hyperkalemia in CHF and the mechanisms of improved K+ homeostasis with training have yet to be established.

Epinephrine

Within-patient correlation between the antihypertensive effects of atenolol, lisinopril and nifedipine.

OBJECTIVE: To investigate whether there are definable subgroups of patients with essential hypertension who respond specifically to particular antihypertensive drugs. DESIGN: Randomized cross-over comparison of the antihypertensive effect of 50 mg atenolol per day, 10 mg lisinopril per day and 20 mg nifedipine retard twice a day. Ambulatory blood pressure monitoring was used to assess the blood pressure level both for recruitment and at the end of each treatment period. The treatment periods lasted 4 weeks and were preceded by 4 weeks of placebo. PATIENTS: Seventy-two untreated hypertensive patients with a mean age of 52 (SD 8.4) years were recruited from six general practices and from the hospital outpatient clinic. Sixty-eight patients completed the trial. MAIN OUTCOME MEASURES: To assess the within-patient correlations among the blood pressure responses to each drug and explore the possible role of simple characteristics, such as the initial blood pressure, plasma renin concentration and age, in identifying the responders to a particular drug. RESULTS: Systolic/diastolic blood pressure fell significantly with each agent (P < 0.001): atenolol reduced it by 16.3 +/- 13.3/9.9 +/- 8.8, lisinopril by 14.8 +/- 15.0/9.4 +/- 9.1 and nifedipine by 11.6 +/- 12.3/6.7 +/- 8.3 mmHg. There was a low degree of correlation between the changes in blood pressure with the three drugs in individual patients. With each drug there was a small percentage (8.9-14.7%) of non-responders. The initial level of systolic blood pressure was weakly correlated with the antihypertensive effect of nifedipine (r = 0.47, P < 0.001) and plasma renin concentration was related to the effect of atenolol (r = 0.32, P < 0.01). Age did not predict the blood pressure response to any agent. CONCLUSIONS: The low level of the correlation between the blood pressure changes with the three drugs suggests that different mechanisms may be involved in the aetiology of essential hypertension. Plasma renin concentration and the initial level of systolic blood pressure contribute only weakly to the identification of responders to the three drugs.

Adolescent

Inherited abnormalities in platelet organelles and platelet formation and associated altered expression of low molecular weight guanosine triphosphate-binding proteins in the mouse pigment mutant gunmetal.

Gunmetal (gm/gm) is a recessively inherited mouse pigment dilution mutant that has high mortality and poor reproductive rates. In these studies, several hematologic defects were found associated with the mutation, including prolonged bleeding times, together with thrombocytopenia and increased platelet size. A unique feature is the presence of simultaneous abnormalities in two platelet organelles, dense granules and alpha-granules. The dense granule component serotonin is present at about half the normal concentration, as are visible dense granules. Three alpha-granule components (fibrinogen, platelet factor 4, and von Willebrand factor) are also significantly reduced. Thus, in several respects the gunmetal mutant resembles the human gray platelet syndrome. A novel abnormality in expression of low molecular weight guanosine triphosphate (GTP)-binding proteins occurs in platelets of gunmetal. In Western blot assays, two additional GTP-binding proteins of 28.5 and 25 Kd were detected. The abnormal expression of GTP-binding proteins is, like the hematologic defects, genetically recessive and is tissue specific. Liver, kidney, brain, spleen, macrophages, and neutrophils have normal GTP-binding protein expression. The additional GTP-binding proteins are soluble. The data indicate that platelet formation and platelet organelle biogenesis are under common genetic control and that abnormal regulation of GTP-binding proteins may affect one or both processes.

Animals

Pre-admission clinic.

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Anesthesia Department, Hospital

Persistent peripheral vasodilation and sympathetic activity in hypotension after maximal exercise.

Hemodynamics (by aortic Doppler), autonomic factors (power spectrum analysis of heart rate and blood pressure variabilities and baroreceptor sensitivity), and plasma renin activity during the hypotension after maximal exercise were studied in 10 normal subjects on two separate days: a nonexercise (control) day (30 min of upright rest followed by 60 min of supine rest) and an exercise day (maximal upright bicycle exercise followed by 60 min supine) in random order. After exercise, diastolic pressure was reduced for the entire hour, cardiac output increased (+33.8%, P < 0.05), stroke volume was unchanged, and systemic vascular resistance fell (-28.6%, P < 0.01). Indexes of vagal activity were reduced for 60 min, whereas the sympathetic indexes were elevated. Baroreflex sensitivity was also reduced for the first 10 min after exercise. Renin activity increased threefold after exercise. The postexercise hypotension results from a persisting peripheral vasodilation despite an increase in renin activity: the persistent sympathetic activity and reduced vagal tone are probably reflex responses to this vasodilatation.

Adult

Low doses of scopolamine increase cardiac vagal tone in the acute phase of myocardial infarction.

BACKGROUND: Reduced cardiac vagal tone in patients with myocardial infarction (MI) is associated with a high risk of sudden death. Muscarinic blocking agents in small doses induce a paradoxical increase in cardiac vagal activity in normal subjects. We tested whether low doses of scopolamine delivered transdermally enhance tonic and reflex cardiac vagal activity in patients in the acute phase of MI. METHODS AND RESULTS: Patients were randomized to a scopolamine (n = 17) or a placebo patch (n = 19) in a double-blind fashion 4.20 +/- 0.18 days after acute MI. Cardiac vagal activity was assessed by testing the arterial baroreflex sensitivity (BRS) using the phenylephrine method and by power spectral analysis of the RR interval variability. Twenty-four hours after scopolamine, we found a significant increase in BRS (from 7.05 +/- 1.21 to 13.99 +/- 2.33 ms/mm Hg, P < .05) and in RR variability, expressed as the mean standard deviation of 512 normal consecutive RR intervals (from 18.09 +/- 2.64 to 31.16 +/- 4.16 milliseconds, P < .05). The amplitude of respiratory sinus arrhythmia, measured by the absolute power of the high-frequency spectral component, was also enhanced (from 62.55 +/- 21.49 to 305.33 +/- 95.68 milliseconds squared, P < .05), whereas the power in the low-frequency spectral component of the RR variability, which results from the interaction between cardiac sympathetic and vagal activity, did not change significantly (from 73.12 +/- 24.44 to 126.46 +/- 44.29 milliseconds squared, P = .93). CONCLUSIONS: In patients in the acute phase of MI, low doses of scopolamine cause a sustained increase in cardiac vagal tone and improve the autonomic indices associated with mortality.

Arteries

Technical note: the development of quality assurance for Sheffield's radiotherapy treatment planning systems.

Quality assurance procedures have been defined and implemented for the treatment planning systems at Weston Park Hospital. The programme of tests and checks covers both hardware and software: hardware checks are concerned with the input and output performance of the system's peripheral devices; the software checks involve testing system data integrity, and testing the algorithms used for planning external photon and electron beams. Beam measurements from an ionization chamber scanned in water and air were compared with calculations from two independent treatment planning systems. Following the implementation of these quality assurance procedures, some improvements have been made to the system data used and changes have been introduced to planning practice.

Algorithms

Effect of circadian variation in energy expenditure, within-subject variation and weight reduction on thermic effect of food.

Thermic effect of food (TEF) studies give conflicting answers to research questions and in many cases data from one laboratory to another is not comparable because of the utilization of different experimental methods. Likewise, how weight reduction affects measurement of TEF is controversial. Two studies were conducted on how TEF affects energy expenditure. The first study examined how resting energy expenditure (REE) measurements can affect TEF studies and how much within-subject variation is found in TEF studies. The TEF of a standard meal was measured in six subjects for 6.5 h on three different occasions by indirect calorimetry. REE was measured on each subject for 1 h before the meal was given on each measurement occasion. On a separate day, the energy expenditure was measured on each subject during the same time period as the TEF measurement, but without any food given to determine if a circadian increase in REE over the time period of the measurement was observed. We found no circadian increase in energy expenditure during the 6.5 h of the REE study. While the within-subject variation in REE (four measurements) had an average coefficient of variation of 5.2% (range 2.4-8.5%), the coefficient of variation of the TEF measured (three measurements) was 26.4% (range 13.6-50.9). In the second study, REF and the TEF were measured before and after weight reduction in moderately overweight adult women. Nine women weighing between 62.1 and 84.7 kg lost an average of 7.3 kg while on a reduced calorie, low fat diet for between 12 and 14 weeks. After weight reduction, the average REE of these subjects decreased by 8.8% or 515 kJ (123 kcal)/24 h. The TEF of these nine women was measured for 6.5 h before and after weight reduction using 16 oz of Sustacal, 2008 kJ (480 kcal). Before weight reduction the thermic effect of Sustacal was 264 kJ (63 kcal) or 13% of calories consumed, and after weight reduction it was 251 kJ (60 kcal) or 12.5% of calories consumed. We did not find the TEF to be lower than expected in these subjects before weight reduction, since TEF is often reported to be around 10% of energy consumed, and it was not changed after weight reduction.

Adult

"Stiff red cell syndrome". A review of the treatment of sickle cell disease with pentoxifylline.

Pentoxifylline has been used extensively to improve microcirculation, particularly in peripheral vascular disease. Pentoxifylline appears to act by increasing red cell flexibility and inhibiting platelet aggregation and white cell adhesion. For that reason, experimental and clinical studies were initiated to explore its possible usefulness in the prevention of vaso-occlusive crises in sickle cell diseases. The current status of such studies is reviewed.

Animals

Antihypertensive effect of carvedilol: a preliminary dose-response study.

The blood pressure (BP) lowering effect of low doses of antihypertensive agents is not usually explored because of the difficulty in detecting small changes in BP. Since ambulatory blood pressure monitoring in a cross-over trial design can reliably detect differences of 5 mmHg with less than 20 subjects, we have used this technique to assess the dose-response curve of a new beta-blocker, carvedilol. Twenty subjects were enrolled after diagnostic ambulatory BP monitoring had shown a day-time average diastolic BP of over 90 mmHg. Three doses of carvedilol (6.25, 12.5 and 25 mg daily) and placebo were then given double-blind in random order for periods of 4 weeks each. No period effects were detected. The antihypertensive effect was statistically significant at doses of 12.5 mg and 25 mg daily. There was, however, no evidence that 25 mg/day produced the peak effect. The lowest dose (6.25 mg/day) produced a small fall in both systolic and diastolic BP but neither of these were significant. We conclude that doses of 12.5 and 25 mg carvedilol once a day are adequate for the treatment of hypertension.

Adrenergic beta-Antagonists

Severe paroxysmal hypertension induced by a subconscious Valsalva-like manoeuvres.

We describe the case history of a 32 year old male with severe paroxysmal hypertensive spikes when there was an increase in diastolic blood pressure to 150-200 mmHg. These spikes occurred during rest and especially during modest exercise. They were associated with headache and dyspnoea and were resistant to antihypertensive medication. After 5 years of observations and investigations he underwent further 24-h intra-arterial blood pressure monitoring and physiological testing. The 24-h blood pressure profile was near normal at rest. The observed hypertensive spikes seemed to be induced by involuntary Valsalva-like manoeuvres. This had not been detected previously by the investigators and the patient was unaware of inducing these manoeuvres.

Adult

Experimental assessment of electrical impedance imaging for hyperthermia monitoring.

Two experimental studies are presented that attempt to assess the use of electrical impedance tomography (EIT) to map thermal changes deep in the body. The first was a joint study between our group in Sheffield and the Daniel den Hoed Cancer Center in Rotterdam, funded by the COMAC-BME Hyperthermia project. Phantom and in vivo experiments were conducted with a deep heating ring-capacitive hyperthermia device; the results highlighted some of the inherent problems (electromagnetic interference, nonuniform sensitivity) that remain to be solved for this application. The second experimental study involved heating the stomachs of volunteers by pumping known quantities of liquid (a salt/glucose solution, conductivity 5 mS) at controlled temperatures (25, 37 and 47 degrees C) in and out of the stomach via a nasogastric tube. Results indicated that the level of thermal change induced by these liquids could be reproducibly measured by impedance imaging. Both studies were a further step in assessing the capabilities of EIT for noninvasive monitoring of deep body hyperthermia. The results are encouraging and indicate the value of continued development of EIT for non-invasive thermometry.

Electric Conductivity

Ascending aortic Doppler velocity and the prediction of exercise capacity in post-infarction left ventricular dysfunction.

A system to improve analysis of the aortic pulsed Doppler velocity signal has been developed and used to study cardiac performance during a 4 min, 25 W incremental stage supine bicycle exercise to exhaustion. Twenty-two male subjects with stable chronic ischaemic heart disease were studied (15 with NYHA class II/III heart failure, and seven age-matched class I subjects). None had evidence of reversible ischaemia. Peak velocity (PV) from the intensity weighted mean velocity profile, early acceleration (eA) and stroke distance (SD) were all significantly lower at rest in class II/III compared to class I. For the change from rest to 50 W, PV did not alter, eAC increased significantly (P less than 0.05) and to a similar extent in both groups (18.6% class II/III vs 16.4% class I) and SD was reduced from 7.8 to 5.9 in class II/III (P less than 0.01) but did not change in class I (12.4 vs 11.8, ns). There was also a greater increase in heart rate (HR) in class II/III subjects (P less than 0.05). The duration of exercise was correlated with resting PV (r = 0.48, P less than 0.025) but was correlated best with the change in blood momentum (PV x Stroke volume x HR) between rest and peak exercise (r = 0.80, P less than 0.001). Thus Doppler velocimetry can give quantitative information on the response to exercise which discriminates between grades of ventricular dysfunction and is predictive of exercise capacity.

Adult

The influence of ambulatory blood pressure monitoring on the design and interpretation of trials in hypertension.

OBJECTIVE: To describe the reproducibility of diastolic blood pressure (DBP) measurement by clinic and ambulatory monitoring and to evaluate the effects of this reproducibility on the design and interpretation of clinical trials in hypertension research. DESIGN: Prospective single-blind study of repeat measurement reproducibility of blood pressure recording. SETTING: Tertiary referral hospital hypertension clinic. PATIENTS: One hundred untreated mild-to-moderate hypertensive subjects taking 1 month of single-blind placebo. MAIN OUTCOME MEASURES: A single clinic measurement of DBP was poorly reproducible and the results for single DBP estimates taken out of a daytime ambulatory recording were similar. Average ambulatory DBP was much more reproducible, although this improvement depended upon the averaging of many measurements taken throughout the day. CONCLUSIONS: Ambulatory monitoring would decrease antihypertensive trial size by a factor of four or halve the size of detectable DBP difference between treatments. The use of poorly reproducible DBP measurements such as single clinic readings may have led to an underestimation of the risks of minor degrees of blood pressure elevation because of a 'regression dilution' bias. For single clinic DBP readings, we calculate this underestimation to be as much as 69%, and for average ambulatory DBP approximately 20%.

Adult