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Biomedical subjects

V Hansteen

Publications and source records attributed to V Hansteen.

At least 19 recordsLinked to original sources

Comparative effects of long-acting and conventional propranolol on stress-induced angina pectoris and on frequency of ventricular premature beats.

Ten male patients with chronic stable angina pectoris completed a randomized, double-blind cross-over study, with matched placebo run-in period (P), to compare the effects of a long-acting preparation of propranolol (LA, 160 mg once a day) with that of conventional propranolol (CP, 40 mg four times a day) each given for 14 days. Response was assessed by symptom-limited bicycle ergometry, degree of ST segment depression, daily anginal attack rate and glyceryl trinitrin consumption (GTN). Heart rate and ventricular extra-systolic frequency (VES) were recorded by 24 h Holter monitor. Bicycle ergometry was performed and a trough blood sample taken for propranolol estimation on day 14 prior to the morning dose. Both formulations increased total work capacity (P 3412, LA 4095, CP 3697 kpm/min), reduced rate-pressure product (P 21896, LA 16011, CP 15609 mm Hg beats/min), and degree of ST segment depression (P 4.53, LA 2.48, CP 2.43), but without differences between the formulations. Daily anginal attack rate was reduced from 30 (placebo) to 7.5 (CP) and 14.5 (LA) (P less than 0.05 between treatment groups). There was a reduction in daily GTN consumption by both treatments. The heart rate and total number of VESs during 24 h was similar in the two treatment groups and was reduced in comparison with placebo. Both formulations were well tolerated. Long-acting propranolol is an effective and well-tolerated alternative to conventional propranolol in the treatment of chronic stable and stress-induced angina, and in reducing VES frequency.

Adult

Beta blockade after myocardial infarction: the Norwegian propranolol study in high-risk patients.

A randomized, double-blind, placebo-controlled trial of propranolol was carried out in 560 high-risk survivors of myocardial infarction enrolled at 12 Norwegian hospitals. The main purpose of the study was to determine the effect of propranolol, 160 mg/day, on the incidence of sudden cardiac death over 12 months. The patients were randomized 4-6 days after the acute event. A statistically significant reduction in sudden cardiac deaths of 52% was noted (11 deaths in the propranolol group and 23 in the placebo group). Four placebo patients and one propranolol patient were successfully resuscitated from ventricular fibrillation. In addition, less severe ventricular arrhythmias were significantly more common among the placebo-treated patients. Twenty-five patients in the treatment group and 37 in the control group died (p = 0.11). Severe adverse effects of the drug were uncommon in this high-risk population. The findings support the results of the Beta-Blocker Heart Attack Trial and other long-term beta-blocker trials in survivors of myocardial infarction.

Adult

One year's treatment with propranolol after myocardial infarction: preliminary report of Norwegian multicentre trial.

A prospective, randomised, double-blind study was performed to compare the effects of propranolol and placebo on sudden cardiac death in a high-risk group of patients who survived acute myocardial infarction. Altogether 4929 patients with definite acute myocardial infarction were screened for inclusion: 574 (11.6%) died before randomisation, and 3795 (77%) were excluded. Five hundred and sixty patients aged 35 to 70 years were stratified into two risk groups and randomly assigned treatment with propranolol 40 mg four times a day or placebo. Treatment started four to six days after the infarction. By one year there had been 11 sudden deaths in the propranolol group and 23 in the placebo group (p less than 0.038, two-tailed test analysed according to the "intention-to-treat" principle). Altogether there were 25 deaths in the propranolol group and 37 in the placebo group (P less than 0.12), with 16 and 21 non-fatal reinfarctions respectively. A quarter of the patients were withdrawn from each group. Withdrawal because of heart failure during the first two weeks of treatment was significantly more common among propranolol-treated patients than among the controls, but thereafter the withdrawal rate was the same. The significant reduction in sudden death was comparable with that after alprenolol, practolol, and timolol, which suggests that the mechanism of prevention is beta-blockade rather than any other pharmacological property of the individual drugs.

Adult

Ergotism in a patient with a portosystemic shunt.

A case of ergotism is described in a patient with Banti's syndrome in whom a porto-systemic shunt had been made three times. She was admitted to hospital with severe ischaemia of the extremities after having taken a single oral dose of 1 mg ergotamine tartrate. Her condition improved rapidly after 2 to 3 days and the circulation was normal after one week. The possible mechanism of ergotism in this patient is discussed. Although the plasma concentration of ergotamine was not measured, the likeliest explanation was that the serious side effects were related to the altered pharmacokinetics and loss of first-pass metabolism of the drug due to the venous bypass of the liver.

Adult

Cardiac arrhythmias in patients with serious pulmonary diseases.

During a 5-year period, 1969-1973, 451 patients with acute severe pulmonary diseases were admitted to the three medical intensive care units (MICU) at Ullevaal Hospital. In 39% of the patients a major cardiac arrhythmia was recorded in the units during a mean observation time of 24 h. The subsequent mortality in the hospital was 31% in patients with arrhythmias in the MICU, and 8% in patients without arrhythmias. The association between arrhythmias and mortality was significant (P less than 0.004) in patients with a diagnosis of pneumonia. There was also an association (P less than 0.04) between arrhythmias and the severity of lung disease. Continuous electrocardiographic monitoring of patients with severe pneumonia or acute exacerbations of obstructive lung disease is recommended.

Acute Disease

Studies on digitalis. XIII. A prospective study of 649 patients on maintenance treatment with digitoxin.

In a prospective study of digitalis intoxication in 649 patients on maintenance treatment with digitoxin a low incidence of digitalis toxicity was found, namely, 5.8 per cent. This is mainly due to a more careful use to digitalis glycosides. It is especially important to reduce the dose of digitoxin in the liver and partly excreted metabolized in the liver and partly excreted through the kidneys as metabolities. Serum half-time of digitoxin is shortened in patients with impaired renal function. Patients with reduced renal function may be treated with digitoxin in the same doses as individuals with normal renal function. This is in contrast to patients treated with digoxin. Digitoxin should therefore be the cardiac glycoside of choice in treatment of patients with renal failure. Digitoxin is further rapidly eliminated in patients with reduced liver function in spite of its extensive hepatic metabolism. In this study extracardia symptoms were found equally often as cardiac signs of toxicity. Patients intoxicated usually had several symptoms and signs of toxicity at the same time. The specificity of commonly used symptoms and signs a digitalis intoxication is very low. In this study atrial tachycardia with block, which has been considered to be an important cardiotoxic arrhythmia, very seldom was found in digitalis intoxication. There is an overlap in digitalis serum concentration between toxic and nontoxic patients. The diagnosis of toxicity was made on clinical grounds. Most of the intoxicated patients had high serum concentrations, but some had concentrations in the normal or low range. Apart from being a guide to the diagnosis of digitalis intoxication, serum digitalis levels may further be a guide to underdigitalization of cardiac patients, especially patients in sinus rhythm.

Age Factors

Studies on digitalis. XIV. Is there any correlation between hypomagnesemia and digitalis intoxication?

In a prospective study on digitalis intoxication, low serum magnesium was found in 90 patients, while 388 patients had values above 1.5 mEq/l. Hypomagnesemia was more frequent in women than in men, in those with low body weight and in those with advanced heart failure. More patients with hypomagnesemia than those without had nausea, anorexia, fatigue, flickering of vision and atrial tachycardia with block. Patients with hypomagnesemia also had lower serum potassium than normomagnesemic patients. There was, however, no significant difference in the prevalence of digitalis intoxication or in serum digitoxin concentration. Nor was there any correlation between serum digitoxin and serum magnesium levels.

Body Weight

Comparison of the acetylation of procainamide and sulfadimidine in man.

The acetylation of procainamide and sulfadimidine has been measured simultaneously in plasma and urine in 20 healthy human volunteers by a specific G.L.C. method, after single and multiple oral dral doses of procainamide retard tablets. A distinct bimodality (9 rapid and 11 slow acetylators) was apparent from the concentrations of procainamide and N-acetylprocainamide both in urine and plasma, which was in complete agreement with data about sulfadimidine acetylation. The influence of acetylator phenotype on the relative concentrations of procainamide and N-acetylprocainamide in plasma as cn 5 additional healthy subjects after a single oral dose of procainamide. The present results show that acetylator phenotype can now be determined using procainamide as the test substance, and for this purpose multiple doses offer hardly any advantage over a single dose of the drug. However, because the separation between rapid and slow acetylators is less pronounced for procainamide than for sulfadimidine, precise criteria must be established for the conditions of the test, and the influence of diseases, such as renal insufficiency, should be taken into consideration.

Acetylation

Maintenance therapy with a new retard tablet preparation of procainamide.

The procainamide plasma concentration was followed during maintenance therapy with a new procainamide retard tablet preparation in 23 hospitalized patients suffering from acute or chronic coronary heart disease with complicating ventricular arrhythmias. After initial individually adjusted treatment with Pronestyl every third hour, either orally or intramuscularly, for at least eight dose intervals, the retard tablets were given at 6 hour intervals for 2 to 12 days, or more. In 19 patients with no major fluctuations in their circulatory or renal state, adequate and relatively stable plasma procainamide concentration was obtained upon a constant dose of the retard preparation. On an average, the difference from minimum to maximum concentration was 55 per cent within the 6 hour dose intervals. In four patients with unstable circulation and/or renal function, procainamide therapy had to be disrupted in two because of severe side effects and toxic concentrations, and the dose was adjusted in the remaining two. It is concluded that the formulation of procainamide tablet preparations has simplified procainamide therapy within and outside hospital and improved our possibilities to perform short-and long-term studies on the risk/ benefit ratio of procainamide treatment in patients with severe ventricular arrhythmias.

Adult

Long-term follow-up of patients with peripheral arterial obliterations treated with arterial surgery.

This paper presents the long-term results of 221 thrombendarterectomy operations during the period 1955-61, and of 86 femoro-popliteal venous bypass operations during the period 1961-64. The indication for surgery was in the majority of the patients disabling claudication. When pain at rest or ulceration was present, arterial reconstruction was performed even when the outlook for a lasting result was poor. Preoperatively a major amputation seemed inevitable in 31 limbs. Thirteen of these are considered to have been saved by the operation. After aortoiliac thrombendarterectomy patent arteries were found in 80% of the extremities after one year and in 48% after 10 years. Forty-five per cent of the extremities were patent on re-examination or remained patent until death. After fermoro-popliteal thrombendarterectomy, 61% of the arteries were patent after one year and 26% after 10 years. Thirty-nine per cent of the arteries were patent on re-examination or remained patent until death. After femoro-popliteal venous bypass, 88% of the grafts were patent after one year and 58% after 5 years. Forty-nine per cent of the grafts were patent on re-examination or remained patent until death. The postoperative mortality was small (4.4% after aortoiliac surgery and 2.0% after femoro-popliteal surgery), and mostly caused by widespread atherosclerosis in other parts of the arterial system. On re-examination 8 to 16 years after the operation, 63% of the patient were dead. Almost 50% of the deaths were caused by coronary heart disease, 17% by cerebrovascular catastrophes, and 13% by other manifestations of atherosclerotic disease. The results are discussed, and it is concluded that long-term results after vascular surgery may be favourable. Peripheral atherosclerosis is, however, a local manifestation of a generalized disease. The indications for reconstructive arterial surgery should therefore be relatively restricted.

Aneurysm