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Biomedical subjects

A Coats

Publications and source records attributed to A Coats.

At least 19 recordsLinked to original sources
PubMed2002

Current evidence supporting the role of diuretics in heart failure: a meta analysis of randomised controlled trials.

OBJECTIVE: To summarise the current evidence from randomised controlled trials for diuretics in patients with congestive heart failure (CHF). DATA SOURCES: English-language randomised controlled trials and review papers referenced in Medline, Embase between 1966 and 1999. General literature review of pertinent journals was carried out and reference lists of papers were inspected. REVIEW METHOD STUDY DESIGN: Meta-analysis of randomised controlled trials of diuretic therapy in patients with CHF. STUDY SELECTION: Studies were included if they were randomised comparisons of loop or thiazide diuretics and control, or one diuretic and another active agent (e.g. ACE inhibitors, ibopamine and digoxin). DATA ABSTRACTION: Using a standardised protocol, two reviewers independently abstracted the data and assessed the methodological quality of each paper. DATA SYNTHESIS: The odds ratio (OR) of treated group compared with control was estimated for each end-point outcome and plotted against each other using the fixed-effects model. THE MAIN OUTCOME MEASURES: The primary outcomes of our analysis were effects of diuretics on mortality and morbidity. RESULTS: Eighteen trials met our criteria and were eligible for analysis, involving 928 patients. Eight trials were placebo-controlled. We analysed the data for mortality and for worsening heart failure. A further ten trials compared diuretics against other agents such as ACE inhibitors, ibopamine, and digoxin. Mortality data were available in three of the placebo-controlled trials (n=221); the mortality rate was lower for patients treated with diuretics than for control [the odds ratio for death, 0.25; 95% confidence intervals (CI), 0.07-0.84; P=0.03]. Admissions for worsening heart failure in the four small trials (n=448) showed an odds ratio of 0.31 (95% CI 0.15-0.62; P=0.001). In six studies of diuretics compared to active control, diuretics significantly improved exercise capacity in patients with CHF [OR: 0.37; CI: 0.10-0.64, P=0.007]. CONCLUSION: Compared to active control, diuretics appear to reduce the risk of worsening disease and improve exercise capacity. The available data from small studies show that in CHF conventional diuretics reduce the risk of death and worsening heart failure compared to placebo.

Diuretics↗
PubMed2001

Effect of environmental factors on the kinetics of insulin fibril formation: elucidation of the molecular mechanism.

In the search for the molecular mechanism of insulin fibrillation, the kinetics of insulin fibril formation were studied under different conditions using the fluorescent dye thioflavin T (ThT). The effect of insulin concentration, agitation, pH, ionic strength, anions, seeding, and addition of 1-anilinonaphthalene-8-sulfonic acid (ANS), urea, TMAO, sucrose, and ThT on the kinetics of fibrillation was investigated. The kinetics of the fibrillation process could be described by the lag time for formation of stable nuclei (nucleation) and the apparent rate constant for the growth of fibrils (elongation). The addition of seeds eliminated the lag phase. An increase in insulin concentration resulted in shorter lag times and faster growth of fibrils. Shorter lag times and faster growth of fibrils were seen at acidic pH versus neutral pH, whereas an increase in ionic strength resulted in shorter lag times and slower growth of fibrils. There was no clear correlation between the rate of fibril elongation and ionic strength. Agitation during fibril formation attenuated the effects of insulin concentration and ionic strength on both lag times and fibril growth. The addition of ANS increased the lag time and decreased the apparent growth rate for insulin fibril formation. The ANS-induced inhibition appears to reflect the formation of amorphous aggregates. The denaturant, urea, decreased the lag time, whereas the stabilizers, trimethylamine N-oxide dihydrate (TMAO) and sucrose, increased the lag times. The results indicated that both nucleation and fibril growth were controlled by hydrophobic and electrostatic interactions. A kinetic model, involving the association of monomeric partially folded intermediates, whose concentration is stimulated by the air-water interface, leading to formation of the critical nucleus and thence fibrils, is proposed.

Anilino Naphthalenesulfonates↗
PubMed2001

The use of ambulatory blood pressure monitoring in managing hypertension according to different treatment guidelines.

OBJECTIVE: To investigate the use of ambulatory blood pressure monitoring (ABPM) in identifying and managing a group of patients referred to a tertiary centre for the assessment of their blood pressure and to illustrate the importance of introducing standardised ABPM treatment guidelines. PATIENTS AND METHODS: We examined 2000 sequential ABP recordings, 1557 were first time referrals from General Practitioners, Consultants and other hospitals. All patients were referred with suspected hypertension, resistant hypertension, white coat hypertension and for investigations of secondary hypertension. Fully trained nurse specialists fitted the monitors in the hypertension clinic and recordings were performed for 24 h. The data was then analysed and stratified according to treatment guidelines and categorised according to different definitions. RESULTS: The group of first time referrals (n = 1557) showed an even sex distribution of 789 men and 768 women, mean age 53 +/- 13.8 (12-88 years). Of this group 542 patients (35%) exhibited a white coat effect (WCE), 526 (34%) had a daytime ABP < or =139/89 mm Hg. Of these 81 (15%) had a high clinic blood pressure (ie, white coat hypertension (WCH)) according to our definition. Thirty-five of these patients were not on treatment but may have had it initiated on the basis of their clinic pressures. According to the British Hypertension Society (BHS) guidelines on clinic readings 772 (45%) of our patients would be classified as hypertensive or inadequately treated, 509 (33%) borderline and 326 (21%) as normal. Using daytime ABP levels according to O'Brien: 1031 (67%) would be defined as abnormal, 192 (12%) as borderline and 334 (21%) as normal. CONCLUSION: These results illustrates how patient management may differ markedly when treating in accordance either with the BHS guidelines for clinic readings or the suggested levels for ABP. More patients had abnormal blood pressure levels according to ABPM, even though it is superior in detecting WCE and WCH. Clear guidelines for ABPM treatment levels need to be established.

Adolescent↗
PubMed2000

Different effects of abnormal activation and myocardial disease on left ventricular ejection and filling times.

BACKGROUND: Ventricular activation is often abnormal in patients with dilated cardiomyopathy, but its specific effects on timing remain undetermined. OBJECTIVE: To investigate the use of the ratio of the sum of left ventricular ejection and filling times to the total RR interval (Z ratio) to dissociate the effects of abnormal activation from those of cavity dilatation. METHODS: Subjects were 20 normal individuals, 11 patients with isolated left bundle branch block (LBBB, QRS duration > 120 ms), 17 with dilated cardiomyopathy and normal activation, and 23 with dilated cardiomyopathy and LBBB. An additional 30 patients (nine with normal ventricular systolic function and 21 with dilated cardiomyopathy) were studied before and after right ventricular pacing. Left ventricular ejection and filling times were measured by pulsed wave Doppler and cavity size by M mode echocardiography. RESULTS: Z ratio was independent of RR interval in all groups. Mean (SD) Z ratio was 82 (10)% for normal subjects, 66 (10)% for isolated LBBB (p < 0.01 v normal), 77 (7)% for dilated cardiomyopathy without LBBB (NS v normal), and 61 (7)% for dilated cardiomyopathy with LBBB (p < 0.01 v normal). In the nine patients with normal left ventricular size and QRS duration, Z ratio fell from 88 (6)% in sinus rhythm to 77 (10)% with right ventricular pacing (p = 0.26). In the 21 patients with dilated cardiomyopathy and LBBB, Z ratio rose from 59 (10)% in sinus rhythm to 74 (9)% with right ventricular DDD pacing (p < 0.001). CONCLUSIONS: Z ratio dissociates the effects of abnormal ventricular activation and systolic disease. It also clearly differentiates right ventricular pacing from LBBB. It may thus be useful in comparing the haemodynamic effects of different pacing modes in patients with or without left ventricular disease.

Bundle-Branch Block↗
PubMed1999

Cardiac effects of exercise rehabilitation in hemodialysis patients.

Exercise training has well documented beneficial effects in a variety of cardiac disorders. End stage renal disease patients present many cardiovascular complications and suffer from impaired exercise capacity. No study to date has adequately examined the cardiac responses to exercise training in renal patients on hemodialysis (HD). To determine the effects of an exercise rehabilitation program on the left ventricular function at rest and during submaximal effort, 38 end-stage renal disease patients on maintenance HD were randomised into three groups. Sixteen of them (group A--mean age 46.4+/-13.9 years), without clinical features of heart failure, participated in a 6-month supervised exercise renal rehabilitation program consisting of three weekly sessions of aerobic training, 10 (group B--mean age 51.4+/-12.5 years) followed a moderate exercise program at home, and the other 12 (group C--mean age 50.2+/-7.9 years) were not trained and remained as controls. The level of anemia and the HD prescription remained constant during the study. Fifteen sex- and age-matched sedentary individuals (group D--mean age 46.9+/-6.4 years) were the healthy controls. All subjects at the start and end of the program underwent physical examination, laboratory tests, treadmill exercise testing, M-mode and 2-D echocardiograms performed at rest and at peak of supine bicycle exercise. Left ventricular volumes (EDV, ESV) and mass (LVM) were measured and ejection fraction (EF), stroke volume index (SVI) and cardiac output index (COI) were calculated by standard formulae. The maximal oxygen consumption increased by 43% (P<0.001) and the exercise time by 33% (P<0.001) after training in group A, by 17% (P<0.001) and 14% (P<0.01), respectively, in B, and both remained unchanged in group C. Training in group A was also associated with an increase in LVIDd (from 52.1+/-6.4 to 54.0+/-6.1 mm, P<0.001) and LVM (226+/-67 to 240+/-84 g, P<0.05) at rest with no change noted in groups B and C. Following a 6-month exercise training in group A an increase was also found in the resting EF by 5% (P<0.01) and SVI by 14% (P<0.001). There was no change found in groups B and C. Supine bicycle exercise after training in group A was associated with an improvement in EF by 14% compared to the pre-training change (P<0.001), SVI by 14% (P<0.001) and COI by 73% (P<0.001). These changes from rest to submaximal exercise were less pronounced in group B following training at home. The untrained patients demonstrated no changes in LV systolic function over the 6-month period. These results demonstrate that intense exercise training improves LV systolic function at rest in HD patients; both intense and moderate physical training leads to enhanced cardiac performance during supine submaximal exercise.

Adult↗
PubMed1999

White coat hypertension detected during screening of male adolescent athletes.

We investigated the utility of the selective use of ambulatory BP monitoring (ABPM) and echocardiography in detecting truly hypertensive adolescents from a cohort of young adolescent athletes undergoing BP screening. A total of 410 athletes (aged 16.4+/-2.6 years) were screened and, if initial BP measurement detected a persistently elevated BP (>140 mm Hg systolic or >90 mm Hg diastolic), ABPM and echocardiography were performed. Eighteen clinically hypertensive cases (4.4%) were detected and evaluated with a 24-h ABPM. Sixteen of them were defined as having "white coat hypertension" because they were detected to have normal daytime and nocturnal BP. An elevated level of BP confirmed on ABPM was recorded in only two (0.5%) athletes. Echocardiography failed to demonstrate significant abnormalities.

Adolescent↗
PubMed1999

The carvedilol hibernation reversible ischaemia trial; marker of success (CHRISTMAS). The CHRISTMAS Study Steering Committee and Investigators.

BACKGROUND: Carvedilol improves left ventricular (LV) function when heart failure is due to LV systolic dysfunction, but the magnitude of the response is heterogeneous among patients with coronary disease, possibly reflecting the presence or volume of hibernating myocardium. AIMS: The primary objective of the study is to determine whether the presence of hibernating myocardium predicts the magnitude of improvement in LV ejection fraction in response to carvedilol among patients with heart failure and LV systolic dysfunction due to coronary disease. METHODS: The study is a prospective, randomised, parallel-group, double-blind, multi-centre study comparing carvedilol and placebo over a period of approximately 6 months in the above patient population. The primary end-point is the comparison of the mean change, from baseline to the final visit, in radionuclide-determined LV ejection fraction among patients on placebo with those on carvedilol stratified according to the presence of hibernating myocardium. Hibernating status will be determined by a combination of echocardiographic and myocardial perfusion (technetium-99m sestamibi) imaging. RESULTS: 255 patients have undergone screening tests of which 207 have been randomised so far. The study intends to randomise 400 patients and the first report of results is expected in 2000. CONCLUSIONS: As far as we are aware this is the first randomised controlled trial to investigate the effects of treatment in patients stratified according to the presence of hibernating myocardium. The study will provide insights into the prevalence of myocardial hibernation, its natural history, and its influence on prognosis as well as the interaction between the presence of hibernating myocardium and the effects of treatment with carvedilol.

Adrenergic beta-Antagonists↗
PubMed1999

Blood Pressure Monitoring. Task force V: White-coat hypertension.

TERMINOLOGY: Two terms are in current use to describe patients whose blood pressures are high only in a medical setting (white-coat hypertension and isolated office or clinic hypertension). The term white-coat effect is also commonly used to describe the pressor response to the clinic setting. DEFINITIONS: White-coat hypertension is generally defined as a persistently elevated clinic blood pressure in combination with a normal ambulatory blood pressure (ABP). There is disagreement regarding the optimal cutoff point for ABP. The white-coat effect is operationally defined as the difference between the clinic blood pressure and daytime ABP. PREVALENCE OF WHITE-COAT HYPERTENSION: This varies according to the definition of white-coat hypertension and the population studied, but is approximately 20% among mild hypertensives, and increases with age. METABOLIC AND BIOCHEMICAL ASPECTS: Authors of some studies have suggested that white-coat hypertension is associated with metabolic abnormalities such as hyperlipidemia that lead to an increase in cardiovascular risk, but most have not found this. TARGET-ORGAN DAMAGE: Several measures of target-organ damage have been compared among normotensives, white-coat hypertensives, and sustained hypertensives; these include left ventricular mass, microalbuminuria, and carotid atherosclerosis. In general, target-organ damage in white-coat hypertension is less than that in sustained hypertension, but in some studies it has been found to be more prevalent than in normotensives. MORBIDITY AND MORTALITY: Authors of a relatively small number of prospective studies have concluded that white-coat hypertensives have a lower risk of morbidity than do sustained hypertensives, but a larger number have drawn the more general conclusion that, when there is a discrepancy between the clinic blood pressure and ABP, the prognosis is more closely related to the ABP. MANAGEMENT: When white-coat hypertensives are prescribed antihypertensive medication there is usually a decrease in clinic blood pressure, but little or no change in ABP. Thus drug treatment is not necessarily indicated. Another issue is the follow-up of white-coat hypertensives; there is general agreement that blood pressure outside the office should be monitored indefinitely. Some patient may have been wrongly classified as white-coat hypertensives, and others may progress to develop sustained hypertension.

Antihypertensive Agents↗
PubMed1999

Assessment of chronic heart failure using gas exchange: which variable and when to correct for body mass.

We investigated whether correction for body mass is appropriate when using variables derived from gas exchange measurements in the assessment of chronic heart failure. Patients with heart failure were studied either on a bicycle ergometer (22 subjects) or on a treadmill (28 subjects). For bicycle exercise testing either peak V(O2) or peak V(CO2) uncorrected for body mass reflected exercise capacity. However, for treadmill exercise, body mass correction was necessary to relate exercise capacity to peak V(O2) or peak V(CO2). Mass correction is therefore appropriate for treadmill but not for bicycle exercise.

Body Mass Index↗
PubMed1996

ACE inhibitors unmask incoordinate diastolic wall motion in restrictive left ventricular disease.

OBJECTIVE: To assess the effect of ACE-inhibition on left ventricular filling and wall motion in patients with a clinical diagnosis of heart failure. DESIGN: Prospective examination of left ventricular systolic and diastolic function using M mode echocardiography and pulsed and continuous wave Doppler before and three weeks after starting an ACE inhibitor. SETTING: A tertiary referral centre for cardiac disease equipped with non-invasive facilities. SUBJECTS: 30 outpatients with a clinical diagnosis of heart failure in whom treatment with an ACE inhibitor was started; age 61 (SD 11) years; 27 male; 3 female; 21 healthy controls of similar age. RESULTS: Left ventricular cavity was dilated both at end systole and end diastole, and fractional shortening reduced. Although mean isovolumetric relaxation time (IVRT) and transmitral E (early) to A (late) filling velocity (E/A) ratio were not different from normal, a value of 1.0 on the normal frequency plot of the E/A ratio divided the patients bimodally into two groups: 20 patients (group A) with E/A ratio > 1.0 and 10 patients (group B) < 1.0. In group A patients, IVRT was short as was transmitral E wave deceleration time compared to normal (P < 0.001), fulfilling the criteria of restrictive left ventricular physiology. Left ventricular wall motion during IVRT was coordinate and left ventricular end diastolic pressure was raised on the apex-cardiogram (P < 0.001). In group B, E wave deceleration time was longer, relaxation incoordinate, and apexcardiogram normal. With an ACE inhibitor: in group A, left ventricular dimensions fell at end diastole (P < 0.05) and end systole (P < 0.01) but fractional shortening did not change; long axis total excursion (P < 0.01) and peak rate of shortening (P < 0.05) both increased; IVRT increased (P < 0.001) with the appearance of markedly incoordinate wall motion, minor axis lengthening, and long axis shortening (P < 0.001 for both); A wave amplitude also consistently increased (P < 0.001); finally, transmitral E wave velocity fell and A wave velocity increased. ACE inhibition did not alter any of the left ventricular minor and long axis or transmitral Doppler variables in patients in group B. CONCLUSIONS: Patients with a clinical diagnosis of heart failure differ in their presentation and response to ACE inhibition according to baseline haemodynamics. In restrictive left ventricular physiology, ACE inhibition reduces cavity size and prolongs IVRT, compatible with a fall in left atrial pressure. At the same time, ventricular relaxation becomes very delayed and incoordinate, greatly reducing early diastolic left ventricular filling velocity. Thus ACE inhibition unmasks major diastolic abnormalities in patients with restrictive left ventricular disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Interruption of the progression of heart failure: are ACE inhibitors the solution?

Our options for the medical management of heart failure are aimed at preventing the development of the condition, relieving symptoms, modifying the underlying pathophysiology, and delaying or preventing disease progression. The principal symptoms of heart failure are edema, dyspnea and fatigue. Diuretics are effective in relieving edema, and dyspnea resulting from pulmonary edema. Once pulmonary edema has been treated relatively few agents are effective against residual exercise-induced dyspnea, possibly because of the numerous possible causes of this symptom. Angiotensin-converting enzyme (ACE) inhibitors have, however, been shown to improve dyspnoea by mechanisms that are not related to hemodynamic actions. These agents also improve skeletal muscle blood flow and function, thereby relieving fatigue in heart failure patients. Treatment strategies aimed at modifying the underlying pathophysiology or preventing disease progression have, with the exception of the ACE inhibitors, met with limited success. Large-scale trials have shown, however, that ACE inhibitors improve survival in patients with moderate or severe heart failure, and prevent the development of heart failure in asymptomatic patients. These agents, therefore, represent an important advance in the management of heart failure, and it is anticipated that new insights into their optimal use will follow as the mechanisms by which they exert their beneficial effects become clear.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Effects of pulsed beta-stimulant therapy on beta-adrenoceptors and chronotropic responsiveness in chronic heart failure.

In animals, intermittent sympathomimetic stimulation with dobutamine produces benefits analogous to those of physical conditioning. Longer intermittent or continuous beta-stimulant therapies have not, however, been successful in managing patients with chronic heart failure. We have investigated the role of beta-receptor stimulants in patients with severe chronic heart failure by changing the method of administration to intermittent, very short-duration pulsed intrope therapy (PIT). We studied 10 patients (mean age 64 [SE 2] years) with stable moderate to severe chronic heart failure (ejection fraction 23 [3]%) who received PIT, and 10 control patients matched for age and severity. We infused sufficient dobutamine to raise heart rate to 70-80% maximum for 30 min per day, 4 days per week for 3 weeks. PIT increased exercise tolerance (from 10.4 [1.2] min at baseline to 13.0 [1.5] min at 3 weeks; p < 0.001, 95% CI for difference 1.6 to 3.9) and lowered peripheral vascular resistance (19.8 [3.1] to 17.7 [2.4] mm Hg.min.L-1; p < 0.05, -4.1 to -0.1). PIT produced significant increases in lymphocyte beta-receptor density (502 [110] to 1200 [219] per cell, p < 0.02, 258 to 1138) and chronotropic responsiveness to exercise (change in heart rest to peak exercise 51.0 [3.2] to 57.5 [3.9] beats per min; p < 0.01, 2.9-10.1). Plasma noradrenaline concentrations (2.39 [0.28] to 1.65 [0.19] nmol/L, p < 0.05) were reduced. The patients' symptoms were also improved. By contrast, no change in autonomic function or exercise capacity was seen in the control group. Short-duration PIT induces pharmacological conditioning with improved symptoms, autonomic balance, exercise tolerance, beta-receptor up-regulation, and enhanced chronotropic responsiveness in chronic heart failure.

Aged↗
PubMed1995

Estrogen acutely increases peripheral blood flow in postmenopausal women.

PURPOSE: To test the acute effect of estrogen on peripheral blood flow and vascular resistance in postmenopausal women. PATIENTS AND METHODS: Eleven normotensive, post-menopausal female volunteers (mean age 53 +/- 6 years) were studied. Six women were in natural menopause and 5 had had a hysterectomy (mean age of the menopause 49 +/- 3 years). We used a double-blind, randomized protocol to assess the acute response to sublingual estradiol-17 beta (1 mg) on the forearm resistance vessels, compared with sublingual placebo. Blood flow was measured by strain-gauge plethysmography, and mean peripheral vascular resistance was then calculated. Mean blood pressure was also measured. RESULTS: The mean blood flow induced by estradiol-17 beta after 40 minutes was significantly greater than that induced by placebo (3.9 +/- 0.5 mL/100 mL per minute versus 2.4 +/- 0.4 mL/100 mL per minute, respectively, P < 0.05). The forearm resistance was significantly reduced at 40 minutes after estradiol-17 beta compared with placebo (25.7 +/- 4.4 resistance units (RU) to 44.4 +/- 6.4 RU, respectively, P < 0.05). Mean blood pressure 40 minutes after the administration of estradiol-17 beta was no different when compared with placebo (91 +/- 1.5 mm Hg versus 90 +/- 2.5 mm Hg, respectively, P = NS). CONCLUSIONS: These results indicate that the acute administration of estradiol-17 beta affects blood flow in the peripheral vasculature in human subjects. The mechanism of this effect has not been determined, but it may explain some of the beneficial effects of estrogen on the vascular system and have future therapeutic potential in postmenopausal women.

Administration, Sublingual↗
PubMed1995

Rat skeletal muscle metabolism in experimental heart failure: effects of physical training.

Skeletal muscle metabolic abnormalities exist in chronic heart failure. The influence of physical training on muscle metabolism after myocardial infarction was studied in a rat model. 31P magnetic resonance spectroscopy and enzyme assays were performed in Wistar rats 12 weeks after coronary artery ligation. Infarcted rats were allocated randomly to either 6 weeks of training or non-training. Spectra were collected from the calf muscles during sciatic nerve stimulation at 2 Hz. Fibre typing and enzymatic assays were performed on the muscles of the contralateral non stimulated leg. Post-mortem rats were also divided into severe and moderate heart failure according to the lung weight per body weight. At 200 g twitch tension, phosphocreatine and pH were found to be significantly lower in the non-trained severe heart failure group compared with the other groups. Phosphocreatine recovery half-time was significantly longer in the non-trained group with severe heart failure and correlated with the citrate synthase activity in the muscle. The training did not induce a change in the enzyme activities in the infarcted animals with moderate heart failure but did correct the lower citrate synthase activity in the non-trained severe heart failure animals. This normalization of muscle metabolism was achieved by training without any change in calf muscle mass, making atrophy unlikely to be the sole cause of the metabolic changes in heart failure. Training in rats with severe heart failure can reverse the abnormalities of skeletal muscle metabolism, implicating decreased physical activity in the aetiology of these changes.

3-Hydroxyacyl CoA Dehydrogenases↗