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Biomedical subjects

M J Kendall

Publications and source records attributed to M J Kendall.

At least 73 records · Page 4Linked to original sources
PubMed1998

Does cholesterol lowering prevent stroke?

The importance of lowering plasma cholesterol to reduce the incidence of coronary events is well established. However, in the prevention of stroke disease, control of hypertension has been the main aim of treatment and lipid lowering therapy has not hitherto been considered to be desirable or necessary. In this review, the evidence from large multicentre trials, imaging studies and meta-analyses is presented. It shows convincingly that HMG-CoA reductase inhibitors (Statins) reduce stroke risk.

Anticholesteremic Agents↗
PubMed1998

An evaluation of the antioxidant activity of a standardized grape seed extract, Leucoselect.

UNLABELLED: Coronary Artery Disease (CAD) remains the major cause of mortality and morbidity in the Western World. The oxidation of low-density lipoproteins (LDLs) by free radicals is associated with initiation of atherosclerosis and therefore, development of CAD. LDLs are protected from oxidation by antioxidants and in times of antioxidant deficiency are more likely to be oxidized. Hypercholesterolaemic patients are at a higher cardiovascular risk and may, therefore, require more antioxidant protection. Increased consumption of red wine containing antioxidants is thought to account for the lower incidence of CAD in Mediterranean countries. Red wine, although rich in antioxidants, is not suitable as routine therapy for prevention of CAD. OBJECTIVE: To evaluate the effects of a capsule formulation of an antioxidant polyphenolic extract of grapes on serum total antioxidant activity and vitamin C and E levels. METHOD: A single-blinded randomised, placebo-controlled cross-over study was undertaken in 20 young volunteers. Subjects were given two capsules containing 300 mg of grape procyanidin extracts (Leucoselect-phytosome) or placebo daily for 5 days. Blood samples were taken at the start of the study and end of the study and assayed for antioxidant activity and vitamins C and E levels. After a washout period of at least 2 weeks, the study was repeated with the second treatment. RESULTS: The extract had no effect on serum vitamins C and E levels but increased serum total antioxidant activity (TAC). On day 5, TAC increased from 408.1+/-22.9 to 453.3+/-453.3 micromol/l trolox equivalents 1 hour postdose. CONCLUSION: The capsules increased serum antioxidant activity but the longer-term clinical implications need to be assessed in further randomised clinical trials.

Adult↗
PubMed1998

Low-density lipoprotein subfraction profiles in chronic renal failure.

BACKGROUND: Small low-density lipoprotein (LDL) particle size, a newly recognized risk factor for cardiovascular disease in the general population, is frequently associated with hypertriglyceridaemia, the predominant plasma lipid abnormality present in uraemia. METHODS: Plasma lipids and LDL subfraction profiles were examined in 33 non-dialysed patients with chronic renal failure (predial), 40 patients on continuous ambulatory peritoneal dialysis (CAPD), 42 haemodialysis patients (HD), 47 renal transplant recipients (RTR), and 44 controls. LDL subfractions separated by gel electrophoresis were scored by densitometric analysis (higher scores indicate profiles comprising smaller particles). RESULTS: All groups with renal failure had significantly elevated (mean+/-SD) LDL scores (predial 1.36+/-0.6, CAPD 1.71+/-0.9, HD 1.68+/-0.9, RTR 1.92+0.8 vs control 0.87+0.4, all P<0.001), this being the only lipid abnormality detected in the predialysis patients. In CAPD and HD patients, LDL scores were associated with serum triglyceride (r=0.81, P<0.001 and r=0.70, P<0.001 respectively), cholesterol (r=0.55, P<0.001 and r=0.49, P<0.01) and HDL-cholesterol (r= -0.43, P<0.01 and r= -0.51, P<0.01), whilst no such relationship was seen in the predialysis and RTR groups, suggesting that other factors were important. CONCLUSIONS: The presence of small LDL particles appears to be an early and unexplained feature of the uraemic dyslipidaemia. This abnormality persists after renal transplantation and may represent an important atherogenic risk factor.

Adrenergic beta-Antagonists↗
PubMed1998

Clopidogrel: secondary prevention of vascular ischaemic events.

Atherosclerotic disease is one of the major causes of premature death. In patients with atherosclerotic disease, antiplatelet therapy with aspirin has been shown to decrease the risk of subsequent events by about 20%. In one large randomized controlled study, clopidogrel showed a marginal benefit over aspirin in the prevention of ischaemic vascular events in high-risk patients. Clopidogrel is therefore an alternative in secondary prevention for those patients who are unable to tolerate aspirin. A literature search was performed using MEDLINE, EMBASE, and the Cochrane library, using the keyword 'clopidogrel'. One published randomized, controlled trial was found which evaluated the effects of clopidogrel in the prevention of vascular ischaemic events.

Clopidogrel↗
PubMed1998

Hypertension in the elderly.

In those aged 65-85 years, the major causes of death and disability are cardiovascular diseases (myocardial infarction, sudden death and stroke). Clinical trials in elderly patients have demonstrated unequivocally that effective blood pressure reduction in hypertensive patients up to the age of 85 years significantly reduces this mortality and morbidity. The larger trials are referred to as the SHEP trial (chlorthalidone), the STOP trial (beta-blockers and/or diuretics), the MRC Elderly Trial (atenolol or diuretic) and the SYST-EUR trial (nitrendipine). Patients entered into clinical trials are a selected population; those with serious coexisting diseases and with a poor prognosis are usually excluded. For this reason one has to carefully consider whether the results of these trials would provide the best treatment for the next patient the doctor sees who would probably not meet the entry criteria. Elderly hypertensives may fall into one of three categories. The sick elderly with serious disorders such as cancer or dementia have a poor quality of life and a bad prognosis. They should not be given antihypertensive drugs. The medically complicated elderly have serious disorders, which usually require drug therapy and the medical condition and the drugs used in treatment may complicate the choice of antihypertensive drugs. The potential adverse effects of adding another form of drug treatment may outweigh the potential benefits. The fit elderly do derive considerable benefit from adequate blood pressure control and need an effective, well-tolerated antihypertensive drug. The choice of drug to control blood pressure in the elderly is difficult. An effective, well-tolerated antihypertensive with little potential to interact with coexisting disorders and other drugs is needed.

Aged↗
PubMed1997

Clinical relevance of pharmacokinetic differences between beta blockers.

Fundamental differences in the pharmacodynamic and pharmacokinetic profiles of beta-adrenergic blocking agents must be considered in optimizing their efficacy and determining the appropriate selection of these drugs in different patients. Beta blockers are contraindicated in patients with asthma and should be used cautiously in heart failure. Clinically important distinctions are related to whether a beta blocker is beta1-selective or nonselective. Most adverse effects of beta-blocker use are related to interference with beta2-mediated functions including bronchodilation, vasodilation, and mobilization of free fatty acids. To achieve the potential benefits of beta1 blockade (decreased heart rate, blood pressure, cardiac workload, and excitability), a low plasma concentration of a beta1-selective drug is required. Adverse effects of beta blockers can be further decreased by selecting a sustained-release beta1-selective drug. Beta blockers are further differentiated on the basis of lipophilicity or hydrophilicity. Lipophilic beta blockers cross the blood-brain barrier, whereas hydrophilic agents do not enter the central nervous system. Some lipophilic agents (metroprolol, timolol, and propanolol) have been shown to decrease mortality in coronary heart disease, particularly sudden cardiac death.

Adrenergic beta-Antagonists↗
PubMed1997

Therapeutic advances: donepezil for the treatment of Alzheimer's disease.

Until recently, few drugs have been available for the treatment of Alzheimer's disease. The first such drug to be launched in the U.K. was the acetylcholinesterase inhibitor, donepezil. The limited published data on donepezil shows only modest cognitive benefit in patients with Alzheimer's disease. The cost of diagnosis and drug treatment, the distressing nature of the disease and the limited evidence available, pose difficult decisions for the introduction of new drugs and the management of this condition.

Alzheimer Disease↗
PubMed1997

Cost analysis of once-daily ISMN versus twice-daily ISMN or transdermal patch for nitrate prophylaxis.

OBJECTIVE: To compare the costs and outcomes of treating exercise-induced angina with once- or twice-daily isosorbide mononitrate (ISMN) or transdermal patch. METHOD: A decision-analytic model was designed based on published literature showing compliance and increasing symptoms and estimates from physicians on treatment patterns and worsening symptoms. RESULTS: Data show that patients are more compliant with once-daily ISMN (Imdur, Astra Hässle, Mölndal, Sweden) and patch regimens than with twice-daily dose. Based upon the assumption that more compliant patients are better controlled, the model found that fewer medical care resources were consumed by patients treated with the once-daily and the patch regimens. The unit cost of the twice-daily ISMN regimen is 40% of the unit cost of the once-daily. Annual costs of treating an exercise-induced angina patient are 248 pounds for Imdur compared to 250 pounds for the twice-daily ISMN and 299 pounds for the transdermal patch. CONCLUSION: Unit prices alone are not good indicators for estimating medical management costs.

Administration, Cutaneous↗
PubMed1997

Beta-blockers in heart failure--a cardioprotective therapy?

Heart failure remains a major cause of morbidity and mortality despite optimum treatment with angiotensin-converting enzyme inhibitors and diuretics. Meta-analysis of recent placebo-controlled, randomized trials suggest that treatment with beta-blockers may significantly reduce mortality by 35%.

Adrenergic beta-Antagonists↗
PubMed1997

The effects of combined treatment with beta 1-selective receptor antagonists and lipid-lowering drugs on fat metabolism and measures of fatigue during moderate intensity exercise: a placebo-controlled study in healthy subjects.

AIMS: We examined the effects of different combinations of beta 1-selective adrenoceptor blockers and lipid-lowering drugs, on fat metabolism and fatigue during moderate intensity exercise in 14 healthy young volunteers. METHODS: The study was a randomized crossover design, each subject completing 5, 90 min walks at 50% of predetermined maximal oxygen uptake (VO2 max), one following each 3 day treatment period with either: atenolol 100 mg and bezafibrate 400 mg, atenolol 100 mg and fluvastatin 40 mg, metoprolol CR 100 mg and bezafibrate 400 mg, metoprolol CR 100 mg and fluvastatin 40 mg, or placebo. RESULTS: Plasma free fatty acid (FFA) concentration during exercise was significantly reduced on all treatments, in comparison with placebo, P = 0.0001. Following 90 min of exercise FFA levels were as follows: placebo 573 mumol l-1 (105-1041), metoprolol CR + fluvastatin 277 mumol l-1 (0-647), metoprolol CR + bezafibrate 182 mumol l-1 (0-396), atenolol + fluvastatin 211 mumol l-1 (0-511), and atenolol + bezafibrate 123 mumol l-1 (0-352). Total fat oxidation during exercise was also reduced on all treatments in comparison with placebo: 38.1% (2-74), compared with 29.1% (0-61) on metoprolol CR + fluvastatin, P = 0.02, 26.2% (2-51) on metoprolol CR + bezafibrate, P = 0.002, 25.5% (3-48) on atenolol + fluvastatin, P = 0.009, and 22.8% (0-47) on atenolol + bezafibrate treatment, P = 0.0002. Plasma ammonia concentration was elevated on all treatments during exercise in comparison with placebo. After 90 min of exercise, plasma ammonia levels were as follows: placebo 37 mumol l-1 (0-84), metoprolol CR + fluvastatin 56 mumol l-1 (2-110), metoprolol CR + bezafibrate 79 mumol l-1 (0-167), atenolol + fluvastatin 90 mumol l-1 (10-170), and atenolol + bezafibrate 100 mumol l-1 26-174). In comparison with placebo, metoprolol CR + fluvastatin had the least adverse impact on measures of perceived exertion and the 'feeling scale' during exercise. Metoprolol CR + bezafibrate, atenolol + fluvastatin, and atenolol + bezafibrate treatments had greater adverse effects, particularly on perceived 'cardiorespiratory effort' and 'feeling scale' scores. CONCLUSIONS: In healthy volunteers, combinations of beta 1-selective blockers and lipid-lowering drugs were associated with significant reductions in fat metabolism, increased plasma ammonia levels, and raised the perception of effort during exercise, in comparison with placebo. Metoprolol CR + fluvastatin had the least effect, combinations metoprolol CR + bezafibrate and atenolol + fluvastatin had intermediate effects, and atenolol + bezafibrate had the most adverse effect.

Adrenergic beta-Antagonists↗
PubMed1997

Therapeutic advances: protease inhibitors for the treatment of HIV-1 infection.

BACKGROUND: Anti-retroviral treatment of human immunodeficiency virus (HIV) infection is undergoing great changes, brought about by a better understanding of the disease pathology. One of the most recent advances has been the introduction of the protease inhibitors, reversible inhibitors of HIV aspartic protease. Published data on the clinical efficacy of these drugs are limited, but preliminary results suggest that, in combination with one or more nucleoside analogues, they represent an important advance in the treatment of patients with advanced HIV infection. The adverse effects and potential for drug interactions, together with the additional cost associated with prescribing these drugs, mean that careful selection and supervision of these patients is imperative. AIM: To present an up-to-date review of the three most recently introduced protease inhibitors. METHODS: Based on a review of the literature, abstracts from relevant meetings and information from the pharmaceutical companies. CONTENT: A review including background data on HIV infection and the treatment options. Detailed information on ritonavir, saquinavir and indinavir. CONCLUSIONS: These new drugs are useful additions to the therapeutic current aims for the treatment of HIV infection. They need to be used under close supervision by specialists.

Anti-Bacterial Agents↗
PubMed1997

The effects of buspirone on perceived exertion and time to fatigue in man.

Male subjects exercised at 80% maximal rate of O2 uptake (VO2,max) following oral administration of either placebo or the partial 5-HT1A agonist buspirone (45 mg), using a paired design. Ratings of perceived exertion were higher following buspirone and time to volitional fatigue (median and inter-quartile range) fell significantly by approximately a third from 26 min (24-30 min) on placebo to 16 min (11-19 min) following buspirone. Serum prolactin was significantly elevated following buspirone administration, indicating increased hypothalamic 5-HT1A receptor stimulation. There were no significant differences in blood lactate or serum glucose between the trials. This study supports the possible central modulation of exercise tolerance by serotonergic pathways, although a role for dopamine cannot be excluded.

Adult↗
PubMed1997

Exercise metabolism in healthy volunteers taking celiprolol, atenolol, and placebo.

OBJECTIVE: Previous studies have shown that beta 1 selective agents have fewer adverse effects on exercise metabolism than nonselective beta blockers, and this has been attributed to their reduced blockade of beta 2 receptors. This study aimed at determining whether a beta blocker with partial agonist activity at beta 1 and beta 2 receptors (celiprolol) was better than a conventional beta 1 receptor-blocker (atenolol) in prolonging exercise capabilities. METHODS: After four days of treatment with celiprolol 200 mg, atenolol 50 mg, or placebo, 22 healthy volunteers exercised on a treadmill for two hours at 50% of their maximal oxygen uptake. Resting heart rate and blood pressure were recorded before and after exercise. During exercise, fat oxidation, plasma free fatty acids, glycerol, glucose, and ammonia were measured together with heart rate and perceived exertion. RESULTS: Mean exercising heart rate was significantly lower in those taking either of the beta blockers than in those taking placebo, and significantly lower for those taking atenolol rather than celiprolol. Fat oxidation was significantly lower for those taking celiprolol (38.8 (SD 12.2)%, P < 0.01) and atenolol (36.6 (15.9)%, P < 0.01) compared with placebo (45.6 (14.1)%). For the first 15 minutes of exercise, fat oxidation was significantly lower for those taking atenolol (24.6 (12.8)%, P < 0.01) than celiprolol (29.6 (14.3)%). The rise in plasma free fatty acids and glycerol during exercise was also significantly attenuated by both beta blockers in comparison with the rise in those taking placebo (P < 0.01). CONCLUSIONS: Both celiprolol and atenolol reduced fat oxidation compared with placebo. For the first 15 minutes of exercise fat oxidation was preserved by celiprolol, but not atenolol. This preservation of fat oxidation during the early part of exercise may confer some small benefit to patients who take beta blockers and intend to exercise regularly. However, we did not detect significant differences between atenolol and celiprolol in overall mean fat oxidation or perceived exertion in this study.

Administration, Oral↗
PubMed1996

Investigation of low density lipoprotein subfractions as a coronary risk factor in normotriglyceridaemic men.

There is an increasing interest in low density lipoprotein (LDL) subfractions since some of them are associated with a higher risk for coronary artery disease (CAD). Small LDL particles are particularly atherogenic and more of those are produced in hypertriglyceridaemia. However, high triglyceride concentrations are not the only explanation for the predominance of small LDL particles and other influences, including genetic factors, are also responsible for LDL particle size. We investigated LDL subfraction profiles in two groups: 46 men with and 21 men without CAD proven angiographically. For the separation of LDL subfractions, we used continuous disc polyacrylamide gel electrophoresis (PAGE) that is rapid and easier to perform than the other methods usually used which, although more precise in terms of measuring particle diameter, are much more demanding of time and equipment. The described method is suitable for routine use in assessing large numbers of patients. All studied men had triglyceride concentrations below 2.3 mmol/l. LDL scores were calculated on the basis of all LDL subfractions present in a particular profile; the higher the score, the greater the proportion of small LDL particles. LDL cholesterol (P < 0.05) and LDL score (P < 0.001) were the only significant discriminators between two groups. LDL score was significantly correlated with CAD, even after adjusting for triglyceride and HDL cholesterol concentrations and it was the best discriminant factor for the presence of CAD.

Coronary Disease↗