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M J Kendall

Publications and source records attributed to M J Kendall.

At least 91 records · Page 5Linked to original sources
PubMed1996

A comparison of the effects of fluvastatin and bezafibrate on exercise metabolism: a placebo-controlled study in healthy normolipidaemic subjects.

1. We have examined the interaction between aerobic exercise and lipid-lowering drugs in a crossover study of 16 healthy normolipidaemic volunteers who each received 21 days' treatment with bezafibrate (400 mg), fluvastatin (40 mg), and placebo, in random order. 2. Fluvastatin treatment reduced pre-exercise total cholesterol (TC) by 23% (P < 0.0001), low-density lipoprotein cholesterol (LDL-C) by 33% (P < 0.0001), and plasma triglycerides by 11%, compared with pre-treatment values. Bezafibrate reduced TC by 11% (P < 0.01); LDL-C by 9%; and plasma triglycerides by 40% (P < 0.01), compared with pre-treatment values. 3. During exercise, in comparison with placebo, and fluvastatin treatment, respectively, bezafibrate significantly reduced mean fat oxidation: 31% vs 39%, P = 0.035, 31% vs 39%, P = 0.002, plasma free fatty acid (FFA) availability, e.g. after 90 min of exercise: (t90) 520 vs 662 mumol 1(-1), P = 0.054, 520 vs 725 mumol 1(-1), P = 0.016, and plasma levels of glycerol (t90): 59 vs 74 mumol 1(-1), P = 0.037, 59 vs 73 mumol 1(-1), P = 0.016. Fluvastatin had no impact on fat metabolism in comparison with placebo. 4. Reduced plasma FFA concentration and lower fat oxidation during prolonged exercise on bezafibrate treatment may be due to an inhibition of hepatic acetyl coenzyme A carboxylase, resulting in reduced FFA release from adipose tissue. 5. The possibility that impaired fat metabolism on fibrates could induce premature fatigue during exercise of moderate duration and intensity should be examined in hyperlipidaemic patients.

Adult↗
PubMed1996

Adverse change in low-density lipoprotein subfractions profile with oestrogen-only hormone replacement therapy.

In a prospective longitudinal study in 17 women, we investigated the effects of surgical menopause and subsequent oestrogen-only hormone replacement therapy (HRT) on plasma concentrations of total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride and LDL subfractions profile. Plasma LDL is a heterogeneous population of particles of varying size, density and chemical composition. The predominance of small LDL particles is a newly-recognized risk factor for coronary artery disease. The LDL score is used to describe LDL subfractions profile and the greater the score, the higher the proportion of small LDL particles. Six weeks after hysterectomy and bilateral oopherectomy, total cholesterol and triglyceride concentrations were significantly increased (p < 0.01) as well as the LDL score (p < 0.05). After 6 weeks of oestrogen-only HRT, total cholesterol concentration was significantly lower and HDL cholesterol concentration significantly higher than before the treatment (p < 0.05). At the same time, mean LDL score significantly increased and in none of the women did LDL subfractions profile change favourably.

Adult↗
PubMed1996

Growth hormone treatment for growth hormone deficient adults.

Growth hormone (GH) deficiency in adults is now recognized as a clinical syndrome with characteristic signs and symptoms. Numerous trials with daily subcutaneous biosynthetic human growth hormone (hGH) have been conducted in this patient group. Generally, improvements in insulin-like growth factor levels, decreases in total fat mass and increases in lean body mass are recorded with no overall effect on total body weight. Variable effects on serum cholesterol, bone mineral density and quality of life have also been reported. The true place of GH replacement therapy in adults has yet to be defined. Several questions relating to the dose, duration of treatment, long-term side-effects, quality of life changes and health economic implications of treatment still need to be assessed.

Adult↗
PubMed1996

Therapeutic advances: riluzole for the treatment of motor neurone disease.

Amyotrophic laterial sclerosis is a fatal neurogenerative disorder, for which only symptomatic treatment was previously available. Riluzole was recently launched in the U.S.A. and Europe. This is the first drug to produce a modest increase in survival (approximately 3 months) in patients with this disease. Unfortunately, treatment causes a number of side-effects of which asthenia is particularly troublesome. Between 10 and 20 per cent of patients can be expected to withdraw from treatment due to these adverse effects. Data on the real time survival advantage and quality of life that can be expected whilst on treatment are needed to identify the place of riluzole in the management of this distressing disease.

Amyotrophic Lateral Sclerosis↗
PubMed1996

Acute effects of beta blockade and exercise on mood and anxiety.

OBJECTIVE: To measure the previously reported beta blocker induced adverse changes in mood state and anxiety measures, and to determine if prolonged aerobic exercise attenuates such mood modifications. METHODS: After 4 days of drug treatment with comparable doses of propranolol (40 and 80 mg), metoprolol (50 and 100 mg), or placebo, mood (POMS) and anxiety states (STAI) were assessed in healthy volunteers, before and after 1 h of treadmill walking exercise at 50% maximum oxygen uptake. RESULTS: Compared to placebo, resting "tension", "depression", and "total mood disturbance" were significantly higher on propranolol 80 mg, but all were reduced with exercise. "Fatigue" and "confusion" were also higher on propranolol, and were unaffected by exercise. "Fatigue" was also higher than placebo after exercise on metoprolol 100 mg. "Anxiety" was unaffected by drug treatment or exercise. CONCLUSIONS: The evidence that beta blockers, and particularly propranolol, have adverse effects on mood was confirmed. It would be preferable to prescribe a beta blocker which does not adversely alter mood states. However, exercise significantly reduced the measures of "tension" and "depression" which were adversely increased by propranolol. Exercise prescription may therefore not only be compatible with beta blockade, but a highly desirable adjuvant therapy.

Adrenergic beta-Antagonists↗
PubMed1995

Beta-blockers and sudden cardiac death.

OBJECTIVES: To 1) consider the problem of sudden death from heart disease and the role of beta-blockers and other agents in preventing sudden death and 2) review perceived problems with beta-blocker therapy, such as effects on blood lipids, complications in diabetes, and adverse effects on heart failure and quality of life. DATA SOURCES: MEDLINE and EMBASE searches done from July 1994 on, and recognized texts. STUDY SELECTION: More than 400 original and review articles were evaluated, of which the most relevant were selected. DATA EXTRACTION: Data were extracted and reviewed by two authors. Accuracy was confirmed, when necessary, by the other authors. DATA SYNTHESIS: Of all of the therapies currently available for the prevention of sudden cardiac death, none is more established or more effective than beta-blockers. Indeed, the evidence that beta-blockers have a cardioprotective effect is compelling. They probably reduce the rate of atheroma formation; they reduce the risk for ventricular fibrillation in animal models of myocardial ischemia; they appear to reduce cardiac mortality in primary prevention trials; and they reduce mortality, particularly from sudden death, in patients who have had infarction. Moreover, withholding beta-blockers because of problems perceived to be associated with them is usually not warranted and may frequently prevent their use in those who will benefit most from them. CONCLUSION: Clinicians should reappraise the evidence for the significant effect of beta-blockers on morbidity and mortality, and they should recognize the importance of initiating and maintaining beta-blocker therapy when the less well-informed might suggest otherwise.

Adrenergic beta-Antagonists↗
PubMed1995

Exercise metabolism during 1 hour of treadmill walking while taking high and low doses of propranolol, metoprolol, or placebo.

Aerobic exercise and beta-blocking drugs are regularly prescribed as treatment for hypertension and as a prophylactic for patients at risk from coronary heart disease and for those recovering from an infarct. Some beta blockers, particularly non-beta 1-selective drugs, may make exercise more difficult, possibly by interfering with substrate metabolism during exercise. This study examined the effects of low and high doses of a beta 1-selective blocker, metoprolol, and a non-selective beta blocker, propranolol, on exercise metabolism. The study involved 20 healthy subjects (10 men, 10 women) who walked on a treadmill at 50% of their maximal oxygen uptake for 1 h on five occasions, separated by 7 days. On each of the five occasions they received one of the following treatments, given in random order: placebo, metoprolol 50 mg, metoprolol 100 mg, propranolol 40 mg, or propranolol 80 mg, all taken twice daily. Fat oxidation, expressed as a percentage of total energy expenditure, was significantly lower than with placebo for all of the active treatments except metoprolol 50 mg (placebo: 42.7 +/- 11.6%; metoprolol 50 mg: 38.7 +/- 14.1%, p = NS; metoprolol 100 mg: 36.3 +/- 13.7%, p = 0.05; propranolol 40 mg: 31.2 +/- 9.3%, p = 0.01; propranolol 80 mg: 29.5 +/- 10.9%, p = 0.01); and significantly lower with propranolol than with metoprolol (propranolol 40 mg: p = 0.0036; propranolol 80 mg: p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Nitrate tolerance.

Explore the source record for details and available documents.

Administration, Cutaneous↗
PubMed1995

Effects of captopril and enalapril on renal function in elderly patients with chronic heart failure.

OBJECTIVE: To compare the effects on renal function of captopril and enalapril in elderly patients with chronic heart failure. DESIGN: A multi-centre double-blind parallel-group comparison of the two angiotensin-converting enzyme (ACE) inhibitors, captopril (12.5 mg bid) and enalapril (2.5 mg bid). SUBJECTS: 80 elderly patients with chronic heart failure (41 in the captopril group, 39 in the enalapril group). MAIN OUTCOME MEASURES: The blood pressure and pulse rate response to the first dose of ACE inhibitor was assessed in all patients. Glomerular filtration rate (GFR) was measured radioisotopically by 99mTcDTPA or 51CrEDTA clearance after three and six months of each treatment. Subgroups were assessed for effective renal plasma flow (33 patients), exercise tolerance (25 patients) and by a symptom-oriented questionnaire (45 patients). RESULTS: No serious adverse effect on GFR was noticed. There was no significant difference between the two treatments in the mean baseline GFR or in changes from baseline at three and six months (captopril mean baseline GFR 49.6 ml min-1 1.76 m-2, enalapril 54.7 ml min-1 1.76 m-2; mean change (95% confidence interval) at three months captopril 12 ml min-1 (+3.0, +21.0), enalapril -2 ml min-1 (-13.0; +9.0); mean change at six months, captopril 3.7 ml min-1 (-6.7; +14.2), enalapril -6.0 ml min-1 (-21.0; +9.4). Significantly more patients given captopril had an improvement in GFR during the study period (26/31 compared with 20/31 enalapril-treated patients at three months, p = 0.0096, and 23/30 compared with 15/27 at six months, p = 0.021). There were no significant changes in effective renal plasma flow. Three patients treated with enalapril developed symptomatic hypotension within three days of starting treatment. Quality of life questionnaires revealed more gastrointestinal symptoms in the enalapril group (p = 0.039). CONCLUSIONS: Captopril seems marginally preferable to enalapril in the treatment of chronic heart failure in elderly patients.

Aged↗
PubMed1995

Approaches to meeting the criteria for fixed dose antihypertensive combinations. Focus on metoprolol.

Fixed dose antihypertensive combinations are being used increasingly in the management of hypertension. There are advantages and disadvantages of this form of therapy. The key aims are to: (i) achieve increased efficacy by using drugs that complement each other's actions; (ii) use low doses to minimise adverse effects; and (iii) provide a simple once daily regimen. Fixed dose combinations containing metoprolol have the advantage that beta-blockers are drugs for which there is most evidence that they are cardioprotective; metoprolol is the best documented beta-blocker in this context. The early combination of conventional release metoprolol and hydrochlorothiazide was inadequately investigated by modern standards, but proved well tolerated and effective in clinical practice. The introduction of the long acting metoprolol CR/ZOK (controlled release/zero order kinetics) produced a very satisfactory once daily preparation with no major pharmacokinetic interactions. The fixed dose combination of felodipine and metoprolol CR/ZOK has been well investigated. The two agents complement each other's actions and together provide very effective blood pressure control, cardioprotection and very good tolerability. A case can be made that this preparation more closely meets the requirements of an ideal antihypertensive than a single agent given alone.

Dose-Response Relationship, Drug↗
PubMed1994

Lack of effect of H2-receptor antagonists on the pharmacokinetics of alcohol consumed after food at lunchtime.

The possibility of a pharmacokinetic interaction between H2-receptor antagonists and alcohol consumed at lunchtime, was investigated in 24 healthy non-alcoholic male subjects, each receiving ranitidine 150 mg four times daily, cimetidine 400 mg four times daily, famotidine 20 mg four times daily and placebo in an open, four-way cross-over study. The subjects consumed 50 g alcohol after a standard lunch on the eighth day of dosing with study medication. Blood samples taken during the 6 h after alcohol consumption were analysed for alcohol concentrations by gas liquid chromatography using head space analysis. None of the H2-receptor antagonists had any statistically significant effects on any of the pharmacokinetic parameters for alcohol. Mean Cmax (95% CI) results for ranitidine were 547 (516, 580), cimetidine 531 (501, 563), famotidine 563 (530, 598) and placebo 529 (499, 561) mg l-1.

Adult↗
PubMed1994

Exercise metabolism in healthy volunteers taking atenolol, high and low doses of metoprolol CR/Z0K, and placebo.

1. Exercise and beta-adrenoceptor blockade have important roles in the prevention and treatment of cardiovascular disease, but fatigue and a reduced capacity to exercise are commonly reported side effects of beta-adrenoceptor blockers. The reduced capacity to exercise may be partly caused by a reduction in fat metabolism. 2. We investigated the effects of atenolol 50 mg, metoprolol CR/Z0K 50 mg, metoprolol CR/Z0K 100 mg and placebo, on heart rate, energy expenditure, fat oxidation, plasma free fatty acids, glycerol, glucose, lactate, ammonia and perceived exertion during 2 h of treadmill walking at 40% of maximal oxygen uptake in 20 healthy volunteers. 3. Compared with placebo (38.0%), total fat oxidation was significantly lower on atenolol 50 mg (30.1%) and metoprolol CR/Z0K 100 mg (31.0%), but not on metoprolol CR/Z0K 50 mg (33.7%). Reductions in fat oxidation correlated well (r2 = 0.970) with reductions in exercising heart rate, and probably reflected the degree of beta 1-adrenoceptor blockade. Maximum plasma ammonia concentration was reached after 45 min of exercise on atenolol, 60 min on metoprolol CR/Z0K 100, and 75 min on metoprolol CR/Z0K 50, and was higher than placebo on all active drug treatments. 4. The greater reduction in fat oxidation with atenolol may be a reflection of a peak in plasma concentration, which is avoided with a controlled release preparation.

Adipose Tissue↗
PubMed1994

Evidence for downregulation of hypothalamic 5-hydroxytryptamine receptor function in endurance-trained athletes.

Serum prolactin (PRL) was used as a hormone marker of serotoninergic function following oral administration of an acute dose of a serotoninergic agonist. Five male endurance-trained athletes (ET) and five healthy non-endurance-trained controls (NT) were studied. The peak PRL concentration was lower (P = 0.031) for the ET athletes (486 +/- 208 mU l-1; mean +/- S.D.) than for the NT controls (1000 +/- 385 mU l-1); the total release of PRL was also lower (P = 0.042) for the ET subjects. The lower neuroendocrine response to a serotoninergic agonist in the endurance-trained athletes suggests a downregulation of central serotoninergic receptor function in response to endurance training in man.

Adult↗
PubMed1994

Corticosteroids: do they damage the cardiovascular system?

Since their introduction for the treatment of rheumatoid arthritis, corticosteroids have become widely used as effective agents in the control of inflammatory diseases. Although there have been undoubted benefits upon mortality in diseases such as systemic lupus erythematosus, many patients survive only to suffer a high incidence of premature atherosclerosis. There is also evidence of increased rates of vascular mortality in other corticosteroid-treated diseases, such as rheumatoid arthritis, reversible airways obstruction and transplant recipients. Possible mechanisms of damage include elevated blood pressure, impaired glucose tolerance, dyslipidaemia, and imbalances in thrombosis and fibrinolysis. This paper reviews the clinical evidence supporting the contention that there is an excess cardiovascular mortality in steroid-treated patients and the underlying mechanisms, and points to further areas of research.

Adrenal Cortex Hormones↗
PubMed1994

A risk-benefit assessment of celiprolol in the treatment of cardiovascular disease.

Celiprolol is a third-generation beta-adrenoceptor blocker with selective beta 1-antagonist, partial beta 2-agonist and mild alpha 2-antagonist actions. It seems to be as effective as other beta-blockers in the treatment of hypertension and angina pectoris. beta-Blockers have many cardioprotective effects and have been shown to reduce the morbidity and mortality from coronary artery disease in a number of trials. However, there is no good clinical evidence that celiprolol itself has specific cardioprotective properties other than those attributable to this class of drugs. Because of its pharmacological profile, celiprolol is less likely to cause bradycardia, deterioration in cardiac function and other adverse effects mainly caused by beta 2-blockade. Unlike most other beta-blockers, celiprolol has no adverse effects on plasma lipids. It seems to be well tolerated in diabetic patients and patients with renal dysfunction.

Adrenergic beta-Antagonists↗