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Biomedical subjects

M H Frick

Publications and source records attributed to M H Frick.

At least 55 records · Page 3Linked to original sources

Angiographic findings in patients exhibiting ischemia after oral dipyridamole.

We have assessed the angiographic features of a group of 37 patients given oral dipyridamole and 37 patients given matching placebo. Both groups represented severe coronary arterial disease and were studied prior to bypass surgery. Six patients (16%) had angina and 13 patients (35%) had electrocardiographic changes after dipyridamole. All the patients in the control group were nonresponders. In the group given dipyridamole the patients responding with angina had significantly more compromised collaterals than the patients without chest pain (P = 0.021). The same applied to the patients with electrocardiographic changes versus those with no electrocardiographic changes (P = 0.034). No differences between responders and nonresponders could be found in terms of the severity of coronary arterial disease, severity of anginal symptoms, exercise tolerance, antianginal medication, number of past myocardial infarctions, and left ventricular ejection fraction. In conclusion, the data strongly suggest that ischaemic responses to dipyridamole originate from myocardial steal accentuated by compromised flow in collateral vessels.

Administration, Oral↗

A dose-response study of amlodipine in mild to moderate hypertension.

The antihypertensive efficacy and suitability for once daily dosing of amlodipine, a new calcium antagonist, was studied in a series of 205 patients with mild to moderate hypertension. The study was conducted double-blind in 13 centres. The starting doses of amlodipine were 1.25, 2.5 and 5 mg, respectively, which were doubled after 4 weeks if normotension or a preset target blood pressure was not reached. Target blood pressure was reached in 25% of patients with placebo, 41% with 2.5 mg of amlodipine, 56% with 5 mg of amlodipine and 73% with 10 mg of amlodipine once daily. The drug was well tolerated at all dose levels and no changes occurred in heart rate, body weight or electrocardiogram during treatment. Amlodipine is a useful new calcium antagonist for the treatment of hypertension producing smooth, dose-dependent blood pressure reductions with convenient once daily dosing.

Adult↗

Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study.

In the Helsinki Heart Study, a randomized five-year, double-blind trial, a 34% reduction in the incidence of coronary heart disease (CHD) was observed in dyslipidemic men treated with gemfibrozil. Averaged over the five years of the trial, gemfibrozil therapy produced, compared with placebo, mean decreases of 10% in serum total cholesterol level, 14% in non-high-density lipoprotein (HDL) cholesterol level, 11% in low-density lipoprotein (LDL) cholesterol level, 35% in triglyceride level, and a mean increase of 11% in HDL cholesterol level from baseline levels measured prior to treatment. While changes in HDL cholesterol level were similar in all Fredrickson types, the effect on concentrations of total cholesterol and LDL cholesterol was largest in type IIA and on LDL minimal in type IV. The reduction of CHD incidence over placebo was largest in type IIB and smallest in type IIA. The lipid changes were dependent on lipid levels prior to treatment and on compliance with the medication regimen. When risk factors for CHD, including age, blood pressure, smoking and drinking habits, baseline lipid levels, and exercise and relative weight, were controlled by applying the Cox proportional hazards model, the changes in serum HDL and LDL cholesterol levels were both statistically significantly associated with the decline in CHD incidence within the gemfibrozil-treated group. The large decrease in serum triglyceride levels had relatively small effect on CHD incidence. Thus, the results of this study, together with earlier observations, suggest that both elevating HDL and lowering LDL cholesterol levels are effective in the primary prevention of CHD.

Adult↗

Helsinki Heart Study. New perspectives in the prevention of coronary heart disease.

The Helsinki Heart Study tested the effect of modifying plasma low density lipoprotein (LDL)- and high density lipoprotein (HDL)-cholesterol on the primary prevention of coronary heart disease in middle-aged men with non-HDL-cholesterol greater than or equal to 5.2 mmol/L (200 mg/dl). One group (2046 men) received 600mg of gemfibrozil twice daily, and the other (2035 men) received placebo. Averaged over the 5-year trial period, gemfibrozil induced mean decreases of 11% in LDL-cholesterol and 35% in triglycerides and a mean increase of 11% in HDL-cholesterol compared with placebo. These changes were accompanied by a 34% reduction (number of end-points; 56 vs 84) in the incidence of coronary heart disease. The reduction was largest in subjects with type IIB hyperlipoproteinaemia and smallest in subjects with type IIA hyperlipoproteinaemia. The changes in serum HDL- and LDL-cholesterol during the trial were associated (p less than 0.02 and p less than 0.05, respectively) with the risk of coronary heart disease in the gemfibrozil group, but not in the placebo group.

Adult↗

Amlodipine: a double-blind evaluation of the dose-response relationship in mild to moderate hypertension.

A multicenter, placebo-controlled trial assessed the antihypertensive efficacy and safety of different doses of amlodipine in patients with mild to moderate hypertension. Amlodipine was administered once daily in doses of 1.25-2.5 mg (low-dose group), 2.5-5.0 mg (medium-dose group), and 5.0-10.0 mg (high-dose group) during 8 weeks; doses were titrated within each group after 4 weeks of double-blind treatment if normotension or "target" blood pressures had not been achieved. After 4 weeks, supine systolic and diastolic blood pressures were significantly reduced in the medium and high-dose groups compared with placebo; standing blood pressures were significantly reduced only in the high-dose group. After 8 weeks of treatment, all blood pressures were significantly reduced except standing systolic and diastolic blood pressures in the low-dose group. There was a low incidence of side effects, which were generally mild to moderate in intensity, and there were no clinically significant effects on pulse rate, electrocardiogram, or body weight. Amlodipine produces a dose-related reduction in blood pressures with once-daily dosing, 2.5 mg being the minimum effective dose, and is well tolerated.

Adult↗

Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease.

In a randomized, double-blind five-year trial, we tested the efficacy of simultaneously elevating serum levels of high-density lipoprotein (HDL) cholesterol and lowering levels of non-HDL cholesterol with gemfibrozil in reducing the risk of coronary heart disease in 4081 asymptomatic middle-aged men (40 to 55 years of age) with primary dyslipidemia (non-HDL cholesterol greater than or equal to 200 mg per deciliter [5.2 mmol per liter] in two consecutive pretreatment measurements). One group (2051 men) received 600 mg of gemfibrozil twice daily, and the other (2030 men) received placebo. Gemfibrozil caused a marked increase in HDL cholesterol and persistent reductions in serum levels of total, low-density lipoprotein (LDL), and non-HDL cholesterol and triglycerides. There were minimal changes in serum lipid levels in the placebo group. The cumulative rate of cardiac end points at five years was 27.3 per 1,000 in the gemfibrozil group and 41.4 per 1,000 in the placebo group--a reduction of 34.0 percent in the incidence of coronary heart disease (95 percent confidence interval, 8.2 to 52.6; P less than 0.02; two-tailed test). The decline in incidence in the gemfibrozil group became evident in the second year and continued throughout the study. There was no difference between the groups in the total death rate, nor did the treatment influence the cancer rates. The results are in accord with two previous trials with different pharmacologic agents and indicate that modification of lipoprotein levels with gemfibrozil reduces the incidence of coronary heart disease in men with dyslipidemia.

Adult↗

Serum lipid changes in a one-year, multicenter, double-blind comparison of doxazosin and atenolol for mild to moderate essential hypertension.

Proatherogenic changes in serum lipid concentrations have been implicated as one of the major risk factors in the development of coronary artery disease. In a double-blind study, the new alpha 1-adrenoceptor inhibitor, doxazosin, was compared with atenolol for effects on the serum lipid profile. Ninety-six hypertensive patients were treated for up to 1 year with either doxazosin or atenolol once daily. There were statistically significant differences (p less than or equal to 0.01) between doxazosin and atenolol after 20 to 52 weeks of treatment in changes from baseline total triglyceride levels, high density lipoprotein (HDL) cholesterol levels and HDL/total cholesterol ratio. The percentage of change from baseline and the statistical significance of the difference between treatment groups were: total triglycerides, doxazosin -5.9%, atenolol +32.4% (p = 0.01); HDL cholesterol, doxazosin +7.2%, atenolol -5.6% (p = 0.007) and HDL/total cholesterol ratio: doxazosin +8.7%, atenolol -6.2% (p = 0.006). All mean changes were in favor of doxazosin therapy. In addition, doxazosin treatment beneficially decreased total serum cholesterol levels (-1.6%) compared with atenolol (+0.6%), although not to a significant degree. The differences were maintained in the cohort of 67 patients treated for a full year. The favorable change exerted by doxazosin on the lipid profile suggests that it may have a beneficial influence on the lipid risk factor. These results, together with the sustained decrease in blood pressure achieved for up to 1 year of therapy, suggest that doxazosin may reduce the risk of coronary artery disease in susceptible patients.

Adrenergic alpha-Antagonists↗

The Helsinki Heart Study: basic design and randomization procedure.

The Helsinki Heart Study is a coronary primary prevention trial in a group of middle aged men with lipid abnormalities. Its aim is to investigate the effects on the incidence of coronary heart disease of simultaneously lowering serum total and low density lipoprotein (LDL)-cholesterol and elevating high density lipoprotein (HDL)-cholesterol with gemfibrozil, over a period of 5 years. Participants were selected from a population of 23 531 men between 40 and 55 years of age. The mean serum total cholesterol among 18 966 screened subjects was 6.3 mmol l-1 (245 mg dl-1) and the mean HDL-cholesterol 1.3 mmol l-1 (50.3 mg dl-1). All subjects meeting the lipid acceptance criterion of non-HDL-cholesterol (i.e. total cholesterol minus HDL-cholesterol) greater than 5.2 mmol l-1 (200 mg dl-1) on two separate occasions two to three months apart, who were free from coronary heart disease or other major illness, were invited to participate. The total cholesterol level for the final 4081 study participants was 7.5 mmol l-1 (290 mg dl-1) and HDL-cholesterol was 1.23 mmol l-1 (47.6 mg dl-1). Mean systolic and diastolic blood pressures were 141.7 and 91.3 mmHg. About 15% of participants were hypertensive and 36% were smokers. A total of 2051 men were randomly allocated to receive gemfibrozil 600 mg twice daily and 2030 matching placebo capsules. A cholesterol-lowering diet was also prescribed for all participants. The randomized treatment groups were well balanced. Equal distribution of major risk factors was achieved in relevant sub-groups. This report describes the procedures involved in setting up the study, summarizes the baseline data obtained and reviews the success of the randomization procedure. Finally, it compares the design of this study with that of some other major preventive trials.

Cholesterol, Dietary↗

Studies on ergometer exercise testing. I. Significance of the type of ST-segment response, sex, and chest pain.

Ergometer exercise electrocardiographic (EECG) data were surveyed in a series of 328 patients (277 men and 51 women) subjected to coronary arteriography. The sensitivity and specificity of EECG for coronary artery disease (CAD) were 84% and 54%, respectively. The predictive accuracy of a positive test for CAD was 95% in men and 81% in women. The predictive accuracy of a negative test was 25% in men and 62% in women. When slowly ascending ST depression was considered insignificant, the sensitivity of EECG declined to 71%, with an increase in specificity to 64%. CAD was present in 89% of the patients with slowly ascending ST depression and 65% of them had a multivessel disease. Seventy-two subjects had postexercise ST-segment elevation. The predictive value of this sign for CAD was 94%. Exercise-induced chest pain had quite a similar diagnostic significance as EECG. The prevalence of CAD in patients with a history of typical angina was 94% in both sexes. Atypical chest pain was associated with normal coronary arteriography in 59% of males and 100% of females.

Adult↗

Studies on ergometer exercise testing. II. Effect of previous myocardial infarction, digoxin, and beta-blockade on exercise electrocardiography.

The results of exercise electrocardiography were studied in a random sample of 317 subjects with clinical suspicion of coronary artery disease. In 278 patients with coronary artery disease the rate of false negative tests was 18% with and 12% without previous myocardial infarction. If ST elevation was considered a negative response, the corresponding values were 25% and 13%, respectively, p less than 0.01. The greatest prevalence of negative tests was seen after anterior myocardial infarction: 27% or 42% when ST elevation was not included into positive responses. The sensitivity of exercise-induced ST depression for the presence of multivessel disease was lower after anterior infarction (67%) than in other patients with previous infarction (86%), p less than 0.01. The corresponding specificities were 71% and 22%, respectively, p less than 0.005. If ST elevation was included into positive responses these differences were abolished. In subjects without myocardial infarction the sensitivity was 89% and specificity 43%. Digitalized patients had somewhat higher sensitivity in the exercise electrocardiogram than those without digoxin, 90% vs. 81% (p less than 0.05), but the difference was not seen with exclusion of ST elevation. The specificity was not influenced by digitalis. beta-blockade had no effect on the sensitivity or specificity, but the prevalence of postexercise ST evolution was lower with (11%) than without (30%) beta-blockade. The prevalence of slowly ascending ST depression was reduced by three factors: the presence of digitalis in patients without previous myocardial infarction, infarction itself, and the extent of coronary artery disease. We conclude that exercise electrocardiography has only a limited value in prediction of multivessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Acute haemodynamic effects of the antiarrhythmic agent pirmenol in cardiac patients: a comparison with lidocaine.

The acute haemodynamic effects of pirmenol, a new Class 1 antiarrhythmic agent, were investigated in a double-blind comparison with lidocaine and placebo. Three groups of 10 patients each received either pirmenol as a 50 mg intravenous injection followed by a 2.5 mg min-1 infusion, or lidocaine as a 75 mg injection followed by a 3 mg min-1 infusion, or placebo. Mean plasma pirmenol concentrations during the 30 min infusion period were 2.3-2.5 mg l-1, and were considered to be therapeutically effective. Compared to measurements taken during a baseline phase of 15 min duration, pirmenol increased heart rate by 10 beats min-1 (P less than 0.001) and mean arterial pressure (MAP) by 5 mmHg (P less than 0.001). It also increased systemic vascular (P less than 0.05) and pulmonary arterial resistances (P less than 0.01). Left ventricular end-diastolic pressure (LVEDP) was not increased significantly. Cardiac index and left ventricular work index remained unchanged. Lidocaine induced a comparable increase in MAP (6 mmHg; P less than 0.001) and elevated LVEDP (2.8 mmHg; P less than 0.05) and did not affect left ventricular work index. Echocardiographic left ventricular ejection fraction was reduced more by pirmenol (-0.05; P less than 0.001) than by lidocaine (-0.03; P less than 0.05), but the greater reduction may partly be explained by the increase in heart rate. Primenol did not induce excessive circulatory responses or side-effects in any patient. Intravenous administration of pirmenol results in increased heart rate and afterload but has little effect on preload. The myocardial depressant effect is relatively slight, and comparable to that of lidocaine.

Adult↗

A long-term double-blind comparison of doxazosin and atenolol in patients with mild to moderate essential hypertension.

The efficacy and safety of doxazosin and atenolol were compared following once-daily administration for up to 1 year, with a minimum of 20 weeks' active treatment. According to response, patients received doxazosin 1-16 mg day-1 or atenolol 50-100 mg day-1. Mean daily doses at the final efficacy assessment (between 20 weeks and 1 year) were doxazosin 11.8 mg and atenolol 94.2 mg. Atenolol produced somewhat greater falls in blood pressure than doxazosin. The differences were statistically significant in the supine but not in the standing position. A small mean reduction in heart rate was produced by doxazosin whereas atenolol produced a marked bradycardia. Analysis of the same patient group at 20 weeks revealed similar overall profiles of activity except that atenolol produced greater falls in blood pressure than in the longer term analysis. Serum concentrations of HDL/total cholesterol ratio were raised in the doxazosin treatment group and lowered in the atenolol group. Triglyceride concentrations fell in the doxazosin group and rose in the atenolol group. Significant differences (P less than 0.001) were observed between treatment groups for these parameters, all differences being in favour of doxazosin. Pharmacokinetics of doxazosin, measured at steady state in 36 patients, showed dose-related plasma concentrations, a mean half-life of about 12 h and relatively low intersubject variation. The incidence of side-effects was slightly greater for patients in the doxazosin group. Drug-related side-effects were mostly mild to moderate in severity with no serious drug-related occurrences in either treatment group. No serious drug-related abnormalities in laboratory biochemistry and haematology tests were observed in either treatment group.

Adult↗

Conversion of paroxysmal atrial fibrillation to sinus rhythm by intravenous pirmenol. A placebo controlled study.

The efficacy of pirmenol (a class I antiarrhythmic agent) as a converter of paroxysmal atrial fibrillation was investigated. Forty patients without congestive heart failure or a history of sinus node disorder were randomly allocated to receive either intravenous pirmenol (50-100 mg) or placebo in a double blind trial. In 12 of 20 patients sinus rhythm was restored 2-16 minutes after pirmenol, and in 3 of 20 patients in the control group it returned within one hour. A nodal escape rhythm was seen during sinus slowing in one patient, but in other patients there was no sinus arrest, atrioventricular conduction disturbance, or hypotension. The ventricular rate was slightly increased in patients in whom sinus rhythm was not restored by pirmenol. The results indicate that pirmenol has an antifibrillatory effect on the atria. Sinus rhythm was restored rapidly after intravenous administration. It was well tolerated in patients with atrial fibrillation of recent onset.

Anti-Arrhythmia Agents↗

Hospital cost development in coronary bypass surgery.

The rapid expansion of open-heart surgery together with steadily rising costs of health services has elicited criticism against uncontrollably expanded costs of coronary bypass surgery. However, critical analyses of the cost structures and the attempts for cost containment can only rarely be found in medical literature. This study emphasizes self-evident surgical principles which have led to surprisingly high cost reductions. Further savings can be obtained by constant financial education of the surgical staff, in spite of some controversial experiences gained elsewhere. The conditions needed are more accurate, up-to-date hospital bookkeeping and closer contacts between the hospital administration and the medical staff.

Coronary Artery Bypass↗

Antiarrhythmic efficacy of pirmenol in the treatment of premature ventricular complexes.

We assessed the antiarrhythmic effectiveness, therapeutic plasma concentrations and adverse effects of pirmenol in 16 patients with frequent (mean 933 h-1) premature ventricular complexes (PVC). Progressive increase in dose to a maximum of 200 mg twice daily suppressed PVC in a majority of patients. By preset criteria 11 patients (69%) exhibited an effective suppression of PVCs whereas in 5 patients (31%) the suppression was inadequate despite therapeutic plasma concentrations. The responders exhibited an 87% mean reduction of PVCs and a 97% reduction in repetitive PVC. This therapeutic effectiveness was verified against placebo by repetitive 24-hour ECG monitorings recorded in a double-blind cross-over fashion. The plasma trough concentration during the effective dose averaged 1.31 +/- 0.67 mg-1 (SD). The efficacy was maintained with the twice daily regimen despite an elimination half life of 6.3 +/- 1.7 h (SD) but a slight decrease in PVC suppression was observed towards the end of the administration interval. Pirmenol was well tolerated but aggravation of the arrhythmia occurred in one patient who shared an associated excessive prolongation of the Q-T interval, a feature observed with quinidine-like class I agents.

Anti-Arrhythmia Agents↗

A sustained effect of coronary bypass surgery in stable angina pectoris.

One hundred patients with angina pectoris were randomly allocated for medical therapy and bypass surgery in groups of 50 patients each. The effect of the respective therapies was assessed by annual exercise testing for up to five years. The surgical group was also studied by postoperative coronary angiograms at three weeks, one year and five years after the operation. The medical group was subjected to repeated coronary angiography five years after randomization. All of the variables depicting exercise tolerance were significantly improved in the surgical group but remained largely at the initial level in the medical group. A subgroup analysis of the surgical series revealed that the sustained improvement was largely confined to the completely revascularized subset of patients. The slowly increasing use of beta blocking compounds in the surgical group also contributed to the favourable results for bypass surgery.

Angina Pectoris↗

Coronary bypass surgery in stable angina pectoris. A randomized study of the effects on morbidity, mortality and employment.

The effects of coronary bypass surgery on morbidity, mortality and employment were assessed in a randomized prospective 5-year study. Exercise tolerance showed an immediate, striking improvement, which was maintained throughout the follow-up period. Corresponding patients treated with medical therapy showed no change. More than 40 percent of patients in the surgical group were free from symptoms over the five years. The annual mortality of the surgical patients was 0.8 percent as compared with 4.0 percent in the medical patients (p less than 0.05). The annual mortality of the intensively treated medical patients with multivessel disease was not significantly higher than the 3.1 percent for a group of patients with single-vessel disease followed concomitantly. The rate of work at 5 years after bypass surgery was 47 percent as compared with only 18 percent in the randomized medically treated group (p less than 0.01). It is concluded that coronary bypass surgery reduces morbidity and mortality and improves employment.

Angina Pectoris↗