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Biomedical subjects

T J Cleophas

Publications and source records attributed to T J Cleophas.

At least 37 records · Page 2Linked to original sources
PubMed2000

Isosorbide mononitrate 30% immediate-release 70% sustained-release formulation: a review. DUMQOL (DUtch Mononitrate Quality of Life) Study Group.

Since the first publication of isosorbide mononitrate 30% immediate-release 70% sustained-release (IR-SR) formulation in 1985, a considerable body of literature concerning its clinical efficacy and safety has become available. Theoretically, the formulation has the advantage over conventional isosorbide mononitrate or dinitrate (ISMN/ISDN) that it has a simpler and more predictable pharmacokinetic profile. The objectives of this paper are to review published data so far and to see whether the theoretical advantages translate into better clinical effectiveness. 1. After oral administration, isosorbide mononitrate IR-SR has a rapid onset of action (30 minutes), and effects are evident for up to 17 hours. 2. The antianginal effects of once-daily isosorbide mononitrate IR-SR increased with increasing dosages, were generally larger than those of either placebo or equipotent doses of conventional ISMN/ISDN, and were somewhat larger than those of the beta blocker bupranolol. The effects were generally similar to those of sustained release nifedipine. 3. Patients showed significantly greater improvement in some quality-of-life indices with once-daily isosorbide mononitrate IR-SR than with twice or three times daily regimens of conventional ISMN/ISDN. This was particularly so with mobility, psychological distress, and life satisfaction indices. 4. Tolerance did not develop after 13 months of once daily isosorbide dinitrate IR-SR. No rebound increase in incidence of ischemic episodes was observed after discontinuation of treatment. 5. Long-term efficacy data both of isosorbide mononitrate IR-SR and of conventional ISMN/ISDN are limited so far. Large studies in patients with angina pectoris and patients with heart failure addressing long-term effects are ongoing, and some of the data will be completed within the next months. Isosorbide mononitrate IR-SR has a rapid onset of action and has been shown to be clinically efficient and, in addition, to be more so than conventional ISMN / ISDN. Nitrate tolerance with continued use of the formulation has not yet been reported. Long-term effects on morbidity and mortality are currently being assessed.

Administration, Oral↗
PubMed2000

Crossover trials should not be used to test one treatment against another treatment with a totally different chemical class/mode of action.

Comparisons of treatments with totally different chemical class/mode of action are at risk of a negative correlation between treatment responses. The crossover design is flawed when correlation between treatment responses is negative. The objective of this study is to assess whether this flaw is prevalent in the literature. Fourteen randomized controlled crossover studies were assessed for correlation levels in relation to their type of treatment comparison. Correlation coefficient (r) was calculated using the t-statistic; p-values were turned into t-values for the degrees of freedom, and r was calculated using the formula for the pooled standard error of the mean (SEM): (pooled SEM)2 = SEM1(2) + SEM2(2) - 2 r SEM1.SEM2. Crossover studies comparing treatments with totally different chemical class/mode of action were frequently negative, and this was obviously due to their correlation between treatment responses' being negative. Crossover studies comparing similar treatments frequently had a positive correlation, and this added extra sensitivity in the treatment comparison; 27% of the crossover hypertension studies compared completely different treatments, and they should not have been performed in the form of a crossover study. The author's conclusion was that crossover trials should not be used to test one treatment against another treatment with a totally different chemical class/mode of action. Crossover trials are particularly sensitive to compare treatments from one chemical class with one mode of action. It is hoped that this work affects the design of future crossover trials.

Clinical Trials as Topic↗
PubMed1999

Wine, beer and spirits and the risk of myocardial infarction: a systematic review.

BACKGROUND: Alcohol has beneficial and harmful effects on health at the same time. Wine may be more beneficial for the heart than other types of alcoholic beverages. OBJECTIVES: 1. To assess the current status of knowledge regarding the relationship between death and alcohol consumption. 2. To assess the relationship between myocardial infarction (MI) and consumption of different types of alcoholic beverages, both low doses (1-4 drinks a day), and high doses (> 4 drinks a day). METHODS: Meta-analysis of major cohort and case-control studies. For the assessment of death and alcohol consumption eight cohort studies were used; for the assessment of MI and different types of alcoholic beverages, 12 cohort and two case-control studies were used. RESULTS AND CONCLUSIONS: 1. Small doses of alcohol (1-4 drinks a day) are associated with a slightly reduced risk of mortality and coronary heart disease (CHD). 2. Small doses (1-4 drinks a day) of wine, beer, and spirits are equally beneficial. 3. Apart from a direct beneficial effect of low doses of alcohol on mortality and CHD, some psychological factors may contribute to its beneficial effect. 4. High doses of alcohol (> or = 5 drinks a day) are not associated with a reduced risk of death and CHD. 5. Apart from a direct effect of alcohol, confounding factors, particularly those of a psychological nature, may very well again contribute to the loss of benefits.

Alcohol Drinking↗
PubMed1999

Combination of calcium channel blockers and beta-adrenoceptor blockers for patients with exercise-induced angina pectoris: a double-blind parallel-group comparison of different classes of calcium channel blockers. Netherlands Working Group on Cardiovascular Research (WCN).

AIMS: The combination of calcium channel blockers and beta-adrenoceptor blockers is more effective for the treatment of exercise-induced angina pectoris than beta-adrenoceptor blocker monotherapy. As ischaemia in exercise-induced angina is preceded by increase in heart rate, calcium channel blockers with negative chronotropic properties may perform better for this purpose than nonchronotropic compounds. METHODS: A 335 patient double-blind parallel-group study comparing 14 day treatment with amlodipine 5 and 10 mg, with diltiazem 200 and 300 mg, and mibefradil 50 and 100 mg added to baseline beta-adrenoceptor blocker treatment was performed. Exercise testing (ETT) was performed by bicycle ergometry. RESULTS: Although none of the calcium channel blockers improved duration of exercise or amount of workload, all significantly delayed onset of 1 mm ST-segment depression on ETT (P<0.001 for any treatment vs baseline). In addition, mibefradil, both low and high dose treatment, produced the longest delays (low dose: different from diltiazem and amlodipine by 24.1 and 29.8 s, respectively, P<0. 003 and <0.001; high dose: different from diltiazem and amlodipine by 33.7 and 37.0 s, respectively, P<0.001 and <0.001). These effects were linearly correlated with the reduction in rate pressure product (RPP). Serious symptoms of dizziness occurred significantly more frequently on mibefradil (P<0.05), and 19 patients on mibefradil withdrew from trial. CONCLUSIONS: Calcium channel blockers with negative chronotropic properties provide greater delay of ischaemia in patients with exercise-induced angina, but the concomitant risk of intolerable dizziness attenuates this benefit.

Adolescent↗
PubMed1999

Replacement of angiotensin-converting enzyme inhibitors by angiotensin-II-receptor antagonists in hypertensive patients with type II diabetes mellitus: metabolic and hemodynamic consequences.

The main pharmacodynamic difference between angiotensin-converting enzyme-inhibitors (ACE-i) and angiotensin-II-receptor antagonists (AII-r) is that ACE-i increase levels of bradykinin, which, in addition to vasodilation, may cause a decrease in insulin resistance. Hypertensive patients with diabetes type II suffering from side effects from ACE-i are frequently changed over to AII-r. The objectives of this study were (1) to study whether this procedure reduces metabolic control, (2) to study effects on blood pressure and forearm blood flow (FLOW), and (3) to study possible associations between the variables hemoglobin A (1c) (HbA(1c)) and FLOW. A self-controlled sequential comparison is required to address such questions. Sixteen patients were treated with 10 mg enalapril or equipotent doses of other ACE-i for 6 months and subsequently with the AII-r losartan at 50 mg daily for 6 more months. Patients were examined at the outpatient clinic every 4 to 8 weeks during the trial. FLOW was measured by iridium strain gauge venous occlusion plethysmography. Mean arterial pressure (MAP) increased by 4 +/- 5 mm Hg (P <.05) after 6 months of losartan treatment as compared with the point of withdrawal of ACE-i. FLOW decreased by 5.4 +/- 5.0 mL/100 mL tissue/min (P <.001), and HbA (1c) increased by 0.6 +/- 0.8 mmol/L (P <.05). Other metabolic variables, including cholesterol, high-density lipoprotein cholesterol, and triglycerides, were not significantly influenced by the change in therapy. Multiple regression analysis revealed that after adjustment for difference in HbA (1c), the correlation between FLOW and MAP was unchanged, and after adjustment for difference in FLOW, the correlation between HbA (1c) and MAP was no longer significant. Replacement of ACE-i by AII-r in hypertensive patients with type II diabetes mellitus induced a significant increase in HbA (1c) and MAP and a decrease in FLOW. The associations of HbA (1c) and FLOW with MAP were at least partly independent of each other, suggesting that mechanisms other than the bradykinin system (eg, the angiotensin (2) -receptor system) are involved. Our study design did not control for placebo and time effects, and so the data are of a preliminary nature.

Adult↗
PubMed1999

Combination of calcium channel blockers and beta blockers for patients with exercise-induced angina pectoris: a double-blind parallel-group comparison of different classes of calcium channel blockers. The Netherlands Working Group on Cardiovascular Research (WCN).

The combination of calcium channel blockers and beta blockers is more effective for the treatment of exercise-induced angina pectoris than beta blocker monotherapy. Since ischemia in exercise-induced angina is essentially preceded by an increase in heart rate, calcium channel blockers with negative chronotropic property may perform better for this purpose than nonchronotropic compounds. A 335-patient, 10-week, double-blind, parallel-group comparison of amlodipine 5 and 10 mg, diltiazem XR 200 and 300 mg, and mibefradil 50 and 100 mg treatment added to baseline beta blocker treatment was performed. Exercise testing (ETT) was performed by bicycle ergometry. Although none of the calcium channel blockers improved duration of exercise or amount of workload, all of them significantly delayed onset of 1 mm ST segment depression on ETT (p<0.001 for any treatment versus baseline). In addition, mibefradil, both low- and high-dose treatment, produced the largest delays (low dose: different from diltiazem and amlodipine by 24.1 and 29.8 s, p<0.003 and <0.001, respectively; high dose: different from diltiazem and amlodipine by 33.7 and 37.0 s, p<0.001 and <0.001, respectively). These effects were linearly correlated to the amount of rate pressure product (RPP) reduction. Serious symptoms of dizziness likewise occurred significantly more frequently with mibefradil (p<0.05) and led 19 patients taking mibefradil to withdraw from the trial. The authors conclude that calcium channel blockers with negative chronotropic property provide better delay of ischemia in patients with exercise-induced angina but that the concomitant risk of intolerable dizziness largely reduces this benefit.

Adolescent↗
PubMed1999

Daytime-selective antihypertensive activity of celiprolol.

Day-activity rhythms of heart rate and blood pressure are thought to be mediated mainly through the sympathetic nervous system and may have greater amplitudes in patients with hypertension owing to increased daytime and largely normal nighttime values. Drug-induced nighttime hypotension in patients with chronic hypertension has been associated with the precipitation of cardiac failure and a fall in cerebral flow. The authors examined the effects of a single dose and of a 4-week treatment with different classes of antihypertensive drugs on ambulatory blood pressure (ABP) in 10 patients with mild hypertension. Data were assessed by polynomial analysis (Harvard Graphics 3). A single oral dose of enalapril 10 mg, amlodipine 5 mg, carvedilol 25 mg, and celiprolol 200 mg produced a mean reduction of 24-hour ABP compared to placebo of, respectively, 24/11, 11/5, 13/6, and 12/5 mm Hg (p values between <0.02 and <0.001). With enalapril, amlodipine, and carvedilol, between-subject variability contributed significantly to the overall variability in the measurements (p values between 0.05 and 0.01 versus zero), whereas with celiprolol this was not so. Although the beta blockers reduced daytime blood pressures similarly to the ACE inhibitor or the calcium channel blocker, they did not reduce nighttime blood pressures. These results were confirmed by an 8-week crossover trial comparing enalapril 10 mg daily with celiprolol 200 mg daily in the same group of patients. The authors conclude (1) that beta blockers produce a more stable reduction of blood pressure in patients with mild hypertension less affected by pressor effects through the sympathetic nervous system; (2) that beta blockers, unlike ACE inhibitors and calcium channel blockers, do not give rise to nighttime hypotension in this category of patients; and (3) that the selective beta blocker celiprolol may even perform better in these respects than the nonselective beta blocker carvedilol.

Administration, Oral↗
PubMed1999

Comparison of 50-mg and 100-mg sustained-release isosorbide mononitrate in the treatment of stable angina pectoris: effects on quality-of-life indices. Dutch Mononitrate Quality of Life (DUMQOL) Study Group.

High-dosage nitrates are more effective for the management of anginal symptoms but produce more adverse effects, including development of tolerance and the zero-hour effect (rebound angina at the end of the dosing interval). Such effects may reduce the beneficial effect of treatment on quality of life. In a self-controlled, 6-month study, the effects on symptoms and quality of life of 50 mg and 100 mg sustained-release isosorbide mononitrate (SR ISMN), administered once daily, on anginal symptoms and quality of life (QOL) were assessed in 453 patients with stable angina pectoris. QOL was assessed by means of a test battery based on the Medical Outcomes Short-Form 36 Health Survey and the Angina Pectoris Quality of Life Questionnaire. The internal consistency and reliability of the multiitem scales were estimated by use of Cronbach's alpha coefficient. Based on their improvements in New York Heart Association (NYHA) angina classification, patients who received 100 mg daily showed greater improvement than those who received 50 mgdaily; the mean difference between treatments was consistent with a significantly greater improvement of mobility and angina indices. Adverse effects, as estimated by side-effect index, including rebound angina at times of rest, and by patient compliance rating, differed slightly between the two treatment regimens and were even less problematic with the higher dosage than with the lower dosage. Psychological distress index and life satisfaction scores also were significantly higher with 100 mg than with 50 mg daily. The results of this study suggest that SR ISMN 100 mg once daily provided a better NYHA angina classification than SR ISMN 50 mg did and did not produce further adverse effects. In addition SR ISMN 100 mg improved various QOL indices more than SR ISMN 50 mg did, particularly the mobility index and certain life satisfaction scores, which are the most important indicators of QOL in this category of patients.

Aged↗
PubMed1999

Combination of calcium channel blockers and beta-blockers for patients with exercise-induced angina pectoris: beneficial effect of calcium channel blockers largely determined by their effect on heart rate.

The combination of calcium channel blockers and beta-blockers is more effective for the treatment of exercise-induced angina pectoris than beta-blocker monotherapy. As ischemia in exercise-induced angina is essentially preceded by an increase in heart rate, calcium channel blockers with a negative chronotropic property may perform better for this purpose than nonchronotropic compounds. A 335-patient, 10-week, double-blind, parallel-group comparison of amlodipine 5 mg and 10 mg, diltiazem 200 mg and 300 mg, and mibefradil 50 mg and 100 mg treatment added to baseline beta-blocker treatment was performed. Exercise testing (ETT) was performed by bicycle ergometry. All of the calcium channels blockers significantly delayed the onset of 1 mm ST-segment depression on ETT (p < 0.001 for any treatment vs. baseline). In addition, mibefradil, in both low- and high-dose treatments, produced the largest delays (low dose: different from diltiazem and amlodipine by 24.1 and 29.8 seconds, respectively, p < 0.003 and < 0.001; high dose: different from diltiazem and amlodipine by 33.7 and 37.0 seconds, respectively, p < 0.001 and < 0.001). A stepwise logistic regression analysis revealed that this beneficial effect of calcium channel blockers was largely dependent on their effect on heart rate. Serious symptoms of dizziness likewise occurred significantly more frequently on mibefradil (p < 0.05 vs. diltiazem) and urged no fewer than 19 patients on mibefradil to withdraw from the trial. The authors conclude that calcium channel blockers with a negative chronotropic property provide a better delay of ischemia in patients with exercise-induced angina, but the concomitant risk of intolerable dizziness may reduce this benefit.

Adolescent↗
PubMed1999

Is selective reporting of clinical research unethical as well as unscientific?

BACKGROUND: Studies that do not confirm their prior hypotheses, otherwise called "negative" studies, receive less interest from different parties including authors, editors and sponsors, and so, not to publish such studies is a common phenomenon. Opinions differ on whether or not this phenomenon introduces imprecision into the assessment of health research and care. OBJECTIVE: The current paper gives arguments against and in favor of publishing "negative" trials, and tries to give suggestions for a more balanced approach to this problem. RESULTS: Arguments against publishing "negative" trials include: we need not publish erroneously "negative" trials; we need not publish a "negative" study out of worry that the favored treatment is inferior; full-length reports of "negative" trials devaluate the quality of literature, because the data are usually not so important, and generally receive little interest from readers, and so, not to publish them is a more or less "natural" matter of course. Arguments in favor of publishing "negative" trials include: no report reduces the flow of information because "negative" trials provide at least some evidence and balance against the overwhelming power of positive data readily accepted for publication; no report violates the promise to patient participants; studies that do not confirm prior hypotheses are especially important; not-publishing leads to unnecessary repetition of research. Initially, trials were frequently "negative" not only due to lack of power but also due to inappropriate hypotheses and poor designs. Currently, this is less so, and the issue of selective reporting, therefore, needs to be reassessed. Suggestions for a more balanced approach to the problem of selective reporting might include: careful planning before the trial begins, reduces the chance of biased and erroneously "negative" trials; any trial, "positive" or "negative", provides probabilities rather than truths; this notion does not explain away publication bias but does make it less of a problem; "negative" trials may not be appropriate for general journals but very relevant to specialist journals as well as other organs of specialist groups; ethical committees and trial review boards should address the issue of publishing as part of their function. CONCLUSION: Data from properly executed trials should routinely be made available. However, we should not forget that the empirical observations provided by clinical trials, are statistically tested, and that statistics are based merely on probabilities. It means that we must consider a more philosophical attitude to clinical trial evidence in terms of acceptance that scientific truths are rarely absolute.

Clinical Trials as Topic↗
PubMed1999

T-channel-selective calcium channel blockade: a promising therapeutic possibility, only preliminarily tested so far: a review of published data. T-Channel Calcium Channel Blocker Study Group.

Basic studies as well as short-term clinical trials of the T-channel-selective calcium channel blocker, mibefradil, are reviewed. The compound reduced afterload and was effective for the symptomatic treatment of hypertension and stable angina pectoris. It did not display any relevant negative inotropic or positive chronotropic effect. Mibefradil has been withdrawn by the manufacturer because of drug interaction at the cytochrome P-450 3A4 enzyme. It is hoped that new T-channel-selective calcium channel blockers will be developed to explore further this promising but so far only preliminarily tested therapeutic possibility.

Angina Pectoris↗
PubMed1998

A randomized, placebo-controlled study of loop diuretics in patients with essential hypertension: the bumetanide and furosemide on lipid profile (BUFUL) clinical study report.

This study was conducted to determine whether loop diuretics are more effective than placebo in reducing blood pressure without raising serum lipid levels, and whether bumetanide is more effective than furosemide in this respect. In a double-blind, 24-week placebo-controlled crossover study, 27 patients with essential hypertension were treated in four periods of 6 weeks each, including placebo twice, furosemide 40 mg daily, and bumetanide 1 mg daily. Several metabolic parameters, including serum lipid levels, and blood pressure were assessed. Overall levels of total cholesterol, triglycerides, and low-density lipoprotein (LDL) cholesterol were 5%, 12.4%, and 4.8% higher, respectively, during loop diuretic therapy than during placebo treatment. Overall systolic and diastolic blood pressure measurements were 12 mmHg and 4 mmHg lower, respectively, during loop diuretic therapy than during placebo treatment. Any added effect of bumetanide on serum lipid levels and blood pressure compared with furosemide, however, could not be confirmed. Our results indicate that the loop diuretics bumetanide and furosemide are effective in reducing blood pressure, and influence serum lipid levels markedly less than do thiazide diuretics or chlorthalidone. In addition, these results indicate that differences in blood pressure reduction and serum lipid levels between the two compounds were small and nonsignificant.

Adult↗
PubMed1998

Depression and myocardial infarction: implications for medical prognosis and options for treatment.

Mental depression and myocardial infarction (MI) are closely related. The current paper reviews pathophysiological mechanisms that could link depression to MI and discusses the pros and cons of different pharmacological and non-pharmacological treatment modalities that could be considered. The selective serotonin reuptake inhibitors lack arrhythmogenic effects, and have a beneficial effect in addition to depression on psychological factors, such as anxiety and mood disturbances, which are not uncommon in post-MI patients. Studies to further determine the impact of depression on the outcome of MI, and the place of different treatment modalities are in progress.

Antidepressive Agents↗
PubMed1998

Crossover studies are a better format for comparing equivalent treatments than parallel-group studies.

BACKGROUND: In controlled clinical trials the new treatment may be a slight modification of the standard or be equivalent to it with the addition of a new component. In this situation there is a positive correlation between the response to the new and the standard treatment. OBJECTIVE: The influence of the correlation between the treatment responses on the statistical sensitivity of testing was studied. Randomized trials of equivalent treatments in psychiatry and hypertension research were studied for their design in relation to their level of correlation. RESULTS: With equivalent treatments and, thus, a positive correlation a paired analysis provides better power than an unpaired one. CONCLUSIONS: Crossover studies are a better format than parallel-group studies for comparing equivalent treatments. The scientific community is technically largely unaware of the mechanisms by which correlation levels influence or lack to influence the statistical power of controlled clinical trials.

Adrenergic alpha-Antagonists↗
PubMed1998

Mechanisms offsetting the beneficial effects of antihypertensive drugs: a problem increasingly considered but incompletely understood.

In clinical practice it is far from uncommon that antihypertensive drugs fail to meet their expectations. This is mainly due to mechanisms counteracting their antihypertensive effects. These mechanisms include stimulation of the sympathetic nervous system (SNS), inhibition of the parasympathetic nervous system (PSNS), stimulation of the renin-angiotensin-aldosterone system (RAAS), as well as endothelium-dependent mechanisms. To review whether the activation of such mechanisms follows differential patterns depending on the type of antihypertensive therapy being used. The antihypertensive effects of diuretics and calcium channel blockers are largely offset by all of the mechanisms enumerated. The antihypertensive effects of angiotensin-converting enzyme (ACE) inhibitors/angiotensin II (AII) receptor antagonists and beta-blockers are counteracted by all of the mechanisms enumerated except for the effects of a stimulated RAAS and SNS, respectively. ACE inhibitors/AII receptor antagonists and beta-blockers display a better profile of mechanisms counteracting their antihypertensive effects than other categories of drugs currently available. However, because this is not routinely confirmed by random trial evidence, additional determinants of drug performance must be considered including between-subject disparities in drug response, metabolic effects, and proliferative effects.

Adrenergic beta-Antagonists↗
PubMed1998

Amplified amplitudes of circadian rhythms and nighttime hypotension in patients with chronic fatigue syndrome: improvement by inopamil but not by melatonin.

Fatigue is an important symptom of a disturbed circadian rhythm. To date, no studies of circadian rhythms in patients with chronic fatigue syndrome (CFS) have been published. The objectives of the study were to study rhythms of heart rate and systolic and diastolic blood pressure in patients with chronic fatigue syndrome compared with age-matched normotensive controls and to study the effects of melatonin and inopamil on such rhythms. Ambulatory blood pressure (ABP) measurements (Space Lab, Inc, validated) of 18 patients with CFS were made according to the 1987 U.S. Center for Disease Control Criteria, and measurements of 12 age-matched normotensive controls were used in a cosinor analysis of the two groups. The effects of melatonin and inopamil on ABP were studied subsequently in four patients in an 8-week open-label evaluation. One patient was hypertensive (diastolic blood pressure > 90 mm Hg at least once every 4 hours), and was, therefore, excluded. The data of the remaining 17 patients (15 women, 2 men) revealed a significant 12-hour rhythm in heart rate and 24-hour rhythm in systolic and diastolic blood pressure with 95% confidence intervals not significantly different from sinusoidal patterns. Although these rhythms were synchronous with the control group rhythms, their amplitudes were not and showed, respectively, 2.8, 2.8, and 9.0 times the size of the control group rhythms (p < 0.001, p < 0.001, and p < 0.0001, respectively). Systolic blood pressures in the patients with CFS were consistently below 100 mm Hg during the nighttime. In a subsequent pilot study of four patients from the study population treated with melatonin 4 mg daily and inopamil 200 mg daily for 4 weeks, inopamil reduced nighttime hypotension (p < 0.05), whereas melatonin increased nighttime hypotension (p < 0.02). Patients with CFS have increased amplitudes of circadian rhythms and systolic blood pressures consistently below 100 mm Hg during the nighttime. Positive inotropic compounds may be beneficial in such patients, but melatonin may not be.

Adult↗