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Biomedical subjects

J F Hansen

Publications and source records attributed to J F Hansen.

At least 73 records · Page 4Linked to original sources
PubMed1994

The prognostic significance of post-infarction angina pectoris and the effect of verapamil on the incidence of angina pectoris and prognosis. The Danish Study Group on Verapamil in Myocardial Infarction.

The prognostic significance of angina pectoris and the effect of intervention with verapamil on the incidence of angina pectoris were studied in patients recovering from myocardial infarction and included in the Danish Verapamil Infarction Trial II. During the second week after admission patients were doubly-blindly randomized to treatment with verapamil 360 mg.day-1 or placebo. Treatment was continued for up to 18 months. At discharge angina pectoris was reported in 11% of 869 patients randomized to verapamil and in 12% of 888 randomized to placebo (ns). One month after discharge a significant increase in the prevalance of angina pectoris was reported in both the verapamil (33%) (P < 0.001) and the placebo groups (39%) (P < 0.001). The one month prevalence of angina pectoris (P = 0.03) and the 18 months overall incidence of angina pectoris (P = 0.002) were both significantly lower in the verapamil group compared with placebo. Stable angina pectoris during the first month of follow-up was a significant predictor of major events (i.e. death or reinfarction) (hazard ratio = 1.45; 95% confidence limits: 1.10, 1.89). As verapamil significantly reduced the incidence of angina pectoris during daily activities, and thereby the number of patients at high risk, the beneficial effect of verapamil in reducing major events in patients recovering from myocardial infarction is likely to be due to abolishing myocardial ischaemia.

Adult↗
PubMed1994

Chronic congestive heart failure. Description and survival of 190 consecutive patients with a diagnosis of chronic congestive heart failure based on clinical signs and symptoms.

The prognosis, and clinical findings related to prognosis, were examined in a consecutive series of 190 patients under 76 years of age (mean 64 years) with congestive heart failure (CHF). The aetiology of CHF was ischaemic heart disease in 66%, hypertension in 11% and cardiomyopathy in 23%. The 2-year mortality was 32%. Median left ventricular ejection fraction (LVEF) was 0.30, range 0.06 to 0.74. Eight per cent were in New York Heart Association (NYHA) class I, 46% in II, 44% in III and 2% in IV. Multivariate analysis, excluding exercise test variables, revealed seven variables with independent, significant prognostic information, (hazard ratios for death in brackets): ln (natural logarithm) (LVEF) (3.19), NYHA class III+IV (2.72), plasma urea > 7.6 mmol.l-1 (2.22), serum creatinine > 121 mumol.l-1 (2.05), serum sodium < or = 137 mmol.l-1 (2.03), pulmonary congestion on X-ray (1.86), and age > 65 years (1.86). Multivariate analysis, including exercise testing, showed the following variables to contain independent, significant prognostic information: increase in heart rate during maximal exercise < or = 35 min-1 (3.5), ln (LVEF) (3.7), serum creatinine > 121 mumol.l-1 (2.9), maximal exercise time < or = 4 min (2.3), serum sodium < or = 137 mmol.l-1 (2.5), ischaemic heart disease (2.0) and plasma urea > 7.6 mmol.l-1 (1.9). In conclusion, patients with CHF have a high risk of death despite intensive medical treatment. LVEF is a strong predictor of mortality. Both NYHA class and exercise variables have strong independent prognostic information as regards mortality in combination with LVEF, but are mutually exclusive.

Adult↗
PubMed1994

Efficacy of anipamil, a phenylalkylamine calcium antagonist, in treatment of angina pectoris.

To evaluate the efficacy of anipamil, a phenylalkylamine calcium antagonist, in treatment of stable angina pectoris, we performed a randomized, double blind placebo-controlled, cross-over study. Inclusion criteria were (a) stable angina pectoris for at least 2 months, (b) an exercise test with > or = 0.1-mV horizontal or downsloping ST-segment depression limited by angina, and (c) at least 10 attacks of angina pectoris in a single-blind 3-week run-in period. Nineteen patients were randomized to enter the study. In 3-week periods, they received either anipamil 80 mg once daily (o.d.), anipamil 160 mg o.d., or placebo. At the end of each period, an exercise test was performed. The number of angina pectoris attacks was significantly reduced during treatment with anipamil 80 mg (p < 0.05) and anipamil 160 mg (p < 0.001) as compared with placebo. Glycerol nitrate consumption was significantly reduced during treatment with anipamil 80 mg (p < 0.01) and 160 mg (p < 0.001) as compared with placebo. During exercise testing, the load (W) at start of angina was significantly increased during treatment with anipamil 80 mg (p < 0.01) and 160 mg (p < 0.05) as compared with placebo. Heart rate (HR) at 0.1 mV ST-segment depression was increased during treatment with anipamil 80 mg (p < 0.001). Few adverse events were reported.

Aged↗
PubMed1994

Ten-year mortality of patients admitted to coronary care units with and without myocardial infarction. Risk factors from medical history and diagnosis at discharge. DAVIT-Study Group. Danish Verapamil Infarction Trial.

The purpose was to evaluate the 10-year mortality in patients with acute chest pain suspected of myocardial infarction with (AMI) and without (non-AMI) confirmed diagnosis and to determine risk factors from the medical history and the diagnosis at discharge. One-thousand eight-hundred and ninety-seven non-AMI patients and 1,401 patients with AMI consecutively admitted to 1 of 16 coronary care units participating in The Danish Verapamil Infarction Study were included. During follow-up, 630 deaths occurred among the non-AMI patients and 415 of these could be classified as cardiac deaths. Multivariate analysis identified the following risk factors containing independent prognostic information about mortality for non-AMI patients: age, previous AMI, sex, and diabetes. In patients with AMI the risk factors were: age, previous AMI, clinical heart failure, diabetes, and angina pectoris. By including the diagnosis at discharge for non-AMI patients in the Cox analysis, the prognostic significance was compared to the variables from the medical history. Only the diagnoses bronchopneumonia, musculoskeletal disorders and observatio sine indicatione therapiae added independent prognostic information. We conclude that non-AMI patients are at high risk for mortal events in the long term. High-risk patients can be identified from their medical history, whereas the diagnosis at discharge only adds limited prognostic information. All non-AMI patients should be carefully evaluated regarding coronary artery disease at the time of discharge in order to improve the risk stratification, treatment and prognosis.

Age Factors↗
PubMed1994

Atherosclerosis in Watanabe heritable hyperlipidaemic rabbits. Evaluation by macroscopic, microscopic and biochemical methods and comparison of atherosclerosis variables.

The spontaneous development of atherosclerotic disease in 38 homozygous and 34 heterozygous Watanabe heritable hyperlipidaemic rabbits was evaluated by qualitative and quantitative light microscopy in aorta, coronary, pulmonary and renal arteries, by naked eye and macroscopic morphometric estimation of aortic atherosclerosis extent and by biochemical analysis of aortic cholesterol content. No noteworthy atherosclerosis was demonstrated within 19 months in heterozygous rabbits. In homozygous rabbits, atherosclerotic lesions were seen from the age of 4 months and progressed with age. All 19-month-old rabbits had severe atherosclerotic disease. As much as 64% of the variation in atherosclerosis extent/severity could be explained by serum cholesterol and age. A highly significant correlation between the various methods for quantitation of atherosclerosis extent and/or severity was demonstrated, suggesting that quantitative microscopy, macroscopic morphometry and determination of aortic cholesterol content may be equally valid as a measure of atherosclerosis in WHHL rabbits and are therefore interchangeable.

Animals↗
PubMed1994

Effect of verapamil on reinfarction and cardiovascular events in patients with arterial hypertension included in the Danish Verapamil Infarction Trial II. The Danish Study Group on Verapamil in Myocardial Infarction.

An increased incidence of reinfarction and cardiovascular events has been reported in patients with hypertension recovering from acute myocardial infarction. We studied the effect of intervention with verapamil on the development of myocardial infarction and cardiovascular events in 301 patients with hypertension enrolled in the Danish Verapamil Infarction Trial II. During the second week after the index infarct, patients were randomly assigned to treatment with verapamil 360 mg per day (n = 149) or placebo (n = 152) and followed-up to 18 months (mean 16 months). The 18 months first reinfarction rates were 12.5% in verapamil and 19.8% in placebo treated patients (hazard ratio 0.53, 95% confidence limits 0.28-1.00, P = 0.04). The first cardiovascular event rates were 21.8% in the verapamil and 29.3% in the placebo group (hazard ratio 0.66, 95% confidence limits 0.41-1.06, P = 0.07). In this retrospective analysis of patients with hypertension included in the Danish Verapamil Infarction Trial II, intervention with verapamil reduced cardiovascular events primarily due to a substantial reduction in reinfarctions.

Aged↗
PubMed1993

The influence of ionic strength and pH on the aggregation properties of zinc-free insulin studied by static and dynamic laser light scattering.

The aggregation properties of zinc-free insulin have been studied using static and dynamic light scattering. The aggregation has been investigated as a function of three parameters, the concentration of sodium chloride (in the range 10-100 mM), the pH value (in the range pH 7.5-10.5), and the insulin concentration (1.8-13.4 mg/mL). The measured homodyne autocorrelation function was used to determine the apparent mean hydrodynamic diameter as well as the apparent weight-averaged molar mass of the insulin species in solution. A method of data analysis was employed, which allows the separation of light scattering contributions from the insulin oligomers and from irrelevant macromolecules and possible impurities present in the sample solutions. Also, a simple phenomenological equilibrium model describing the association of oligomers of insulin is presented. One aspect of this model is that it makes it possible to determine weight average molar masses corrected for virial effects on the Rayleigh ratio. This was necessary because virial effects cannot be isolated and corrected for by dilution since this would change the equilibrium distribution of oligomers. The basis of the model is a positive contribution to Gibbs free energy from charge repulsion depending on the protein charge and the number of monomers in the oligomers, and an assumed constant negative contribution to Gibbs free energy arising from either an entropic gain or hydrogen bonding upon association. The equilibrium model gives a good description of both the apparent weight average molar masses and the apparent hydrodynamic diameters, when the effect of the insulin concentration is taken into account by including virial effects arising from charge-charge repulsion (Donnan effect). The result shows that the association of insulin as a function of pH and ionic strength can be described by an effective charge equal to the charge derived from proton titration reduced by the number of sodium ions binding to insulin. At the lowest pH and highest salt concentration (pH 7.5, 100 mM NaCl, 12 mg/mL insulin), the weight average molar mass is close to that of the hexamer, and at the highest pH and lowest salt concentration (pH 10.5, 10 mM NaCl, 1.9 mg/mL), the weight average molar mass is close to that of the monomer. In all cases, however, a distribution of oligomers is present with a relative Gaussian width of about 30%.(ABSTRACT TRUNCATED AT 400 WORDS)

Chemical Phenomena↗
PubMed1993

Mortality of patients excluded from the Danish Verapamil Infarction Trail II. The DAVIT-II Study Group.

The 18 month mortality rate in 2180 patients excluded from the Danish Verapamil Infarction Trail II (DAVIT II) was 25.6%. In non-consenters (n = 368) this was 15.0% compared with 13.85 in 897 placebo-treated patients (hazard ratio 1.09 [P = 0.60] when adjusting for sex and age). The increased mortality rate in excluded patients is attributed to heart failure (45.8%) and other severe diseases (38.9%).

Adrenergic beta-Antagonists↗
PubMed1993

Postinfarct treatment with verapamil. Effect of verapamil in patients with hypertension.

In the Danish Verapamil Infarction Trial II (DAVIT II), treatment with verapamil 360 mg/day improved reinfarction-free survival compared with administration of placebo. Verapamil appears to effectively prevent reinfarction and sudden death, i.e. sudden events (hazard ratio 0.78 compared with placebo, 95% confidence limits 0.62 to 0.99). In a retrospective analysis of data from DAVIT II, verapamil treatment in patients with systemic hypertension prevented reinfarction significantly better than placebo (15 of 149 verapamil recipients compared with 27 of 152 placebo recipients reinfarcted, p = 0.04). Similarly, first cardiovascular events, i.e. first reinfarction, first stroke or death, were prevented more effectively by verapamil treatment than by administration of placebo (29 verapamil recipients vs 42 placebo recipients had first cardiovascular events, p = 0.07).

Cerebrovascular Disorders↗
PubMed1992

[Verapamil therapy improves the prognosis after acute myocardial infarction. A review over the Danish studies of verapamil therapy during and after acute myocardial infarction].

The effect of verapamil therapy in a dosage of 120 thrice daily on the mortality and re-infarction from the time of admission and for the subsequent six months was investigated in a double-blind, randomized, placebo-controlled, multicentre investigation (The Danish Verapamil Infarction Trial (DAVIT I)). Seven hundred and seventeen patients were treated with verapamil and 719 with placebo. The mortalities after six months were 12.8% in the verapamil group and 13.9% in the placebo group (NS) and re-infarction occurred in 7.0% and 8.3%, respectively (NS). The effect of verapamil on the mortality and major events, i.e. death or the first re-infarction from the second week after an acute myocardial infarction was investigated in a double-blind, randomized, placebo-controlled, multicentre investigation (DAVIT II) in which 878 patients commenced treatment with verapamil in a dosage of 360 mg daily and 897 patients received a placebo. This treatment was continued for up to 18 months, on an average for 16 months. Ninety-five patients died and 146 major events were registered in the verapamil group while 119 died and 180 major events occurred in the placebo group. The 18 months mortality rates were 11.1 and 13.8% (hazard ratio 0.80, 95% confidence limits 0.63-1.05, p = 0.11) and the major event rates were 18.0 and 21.6% (0.80, 0.64-0.99, p = 0.03) in the verapamil and placebo groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Denmark↗
PubMed1992

The significance of myocardial ischaemia and verapamil treatment on the prevalence of supraventricular tachyarrhythmias in patients recovering from acute myocardial infarction. Danish Study Group on Verapamil in Myocardial Infarction.

Twenty-four hour Holter monitoring and symptom-limited exercise testing were carried out prior to discharge in 157 patients recovering from acute myocardial infarction. Supraventricular arrhythmias (SVT) during Holter monitoring were recorded in 15%, and ST segment depression during exercise in 27%. No association between exercise-provoked ischaemia and SVT was found in the late hospital phase of myocardial infarction. After the tests, patients were double-blindly randomized to treatment with verapamil 120 mg t.i.d. or placebo. One month after randomization 24 h Holter monitoring was repeated in 125 patients (verapamil = 63, placebo = 62). At one month a significantly increased incidence of SVT was found in the placebo group (25%) compared to the verapamil-treated patients (9%) (P = 0.04). The increased prevalence in the placebo group was mainly due to an increased incidence of SVT in patients with exercise-induced ischaemia (P = 0.03). This increment was blurred in the verapamil group. In conclusion, the prevalence of SVT increases during the first month after myocardial infarction. The increase is most pronounced in patients with residual myocardial ischaemia and seemed to be prevented by treatment with verapamil.

Double-Blind Method↗
PubMed1992

Prevalence of transient myocardial ischaemia during the first year after a myocardial infarction. Effect of treatment with verapamil. The Danish Study Group on Verapamil in Myocardial Infarction.

DAVIT-II is a double-blind, randomized, multicentre, placebo-controlled study of long-term treatment with verapamil 360 mg per day administered to patients who have suffered an acute myocardial infarction (AMI). In the present study, comprising a subset of DAVIT-II, 48 h continuous ECG recordings demonstrated transient ST segment deviation indicative of myocardial ischaemia after one week, prior to randomization, in 18% (10 of 57) of the patients. After one month, 24% (11 of 46) of the placebo and 8% (3 of 39) of the verapamil-treated patients (P = 0.04) had myocardial ischaemia; after one year the figures were 26% (9 of 35) and 4% (1 of 27) (P = 0.02), respectively. At 18 months the 'major' event rate in patients who had had ischaemia before randomization was 40% and 23.8% in patients without ischaemia (P = 0.057). In the placebo group, 63% of 91 episodes of ST depression were recorded between 0600 h and 1800 h, and 62% of 26 episodes of ST elevation between 1800 h and 0600 h (P less than 0.001). Nine episodes of ST depression and no episode of ST elevation were recorded in the verapamil-treated patients. In conclusion, 20-25% of post-AMI patients have transient ischaemia; verapamil prevents ischaemia, and a pronounced circadian variation of ST segment deviations can be demonstrated.

Aged↗
PubMed1992

Secondary prevention with calcium antagonists after acute myocardial infarction.

Experimental studies have demonstrated that the 3 calcium antagonists nifedipine, diltiazem, and verapamil have a comparable effect in the prevention of myocardial damage during ischaemia. Secondary prevention trials after acute myocardial infarction, which aimed at improving survival and preventing reinfarction, nevertheless demonstrated pronounced differences between the 3 drugs. Nifedipine had no effect on reinfarction or death. Diltiazem had no overall effect but prevented first reinfarction or cardiac death (cardiac events) in patients without heart failure, and increased cardiac events in patients with heart failure before randomisation. Verapamil prevented first reinfarction or death (major events); the most pronounced effect was found in patients without heart failure before randomisation. Verapamil did not have detrimental effects in patients treated for heart failure before randomisation. Differences between trials and between drugs explaining the different clinical findings are evaluated.

Adrenergic beta-Antagonists↗
PubMed1992

Insulin analogues with improved absorption characteristics.

The insulin preparations available today are not ideal for therapy as s.c. injection does not provide a physiological insulin profile. With the aim to improve the absorption properties recombinant DNA technology has been utilized to design novel insulin molecules with changed physico-chemical characteristics and hence altered subcutaneous absorption kinetics. Soluble, long-acting human insulin analogues in which the isoelectric point has been increased from 5.4 to approx. 7 are absorbed very slowly, providing a more constant basal insulin delivery with lower day-to-day variation than present protracted preparations. In addition they have better storage stability. Rapid-acting human insulin analogues with largely reduced self-association are absorbed substantially faster from subcutaneous tissue than current regular insulin and thus are better suited for bolus injection. The absorption kinetics of these analogues have been able to explain the mechanism behind the dose effect on insulin absorption rate.

Absorption↗
PubMed1991

Physiological and pathophysiological pulmonary responses to inhaled nuisance-like or fibrogenic dusts.

A short-term bioassay has been developed to assess pulmonary toxicity and predict pathological effects in animals exposed to aerosolized particulates. To test the reliability and predictive value of our bioassay, we have exposed rats to 2 materials with different biological activities. Rats were exposed for 1 or 3 days to selected concentrations of crystalline silica (a known fibrogenic dust), or to carbonyl iron (CI) particles (a material with activity reputedly similar to nuisance dusts). Pulmonary cells and tissues were evaluated at several time points after exposure. In a companion manuscript we reported that brief exposures of silica produced a sustained pulmonary inflammatory response, characterized by increases in biochemical indicators, whereas no significant effects were measured in CI-exposed animals. In the current study, our results showed that although deposition patterns for the 2 dusts were similar (i.e., at alveolar duct bifurcations), brief doses of silica produced a sustained granulocytic inflammatory response at the sites of particle deposition, while CI particles were phagocytized and cleared from the lung by normal pulmonary macrophage mechanisms which included transport via the airway mucociliary escalator. Light, scanning, and transmission electron microscopy of silica-exposed lung tissue revealed a chronically active pulmonary inflammatory response characterized by hyperplasia of type II alveolar epithelial cells and the infiltration of pulmonary macrophages and neutrophils into interstitial tissues and alveoli. The lesions were progressive leading to a granulomatous pneumonitis within 2 months postexposure. In contrast to the alterations in pulmonary tissues produced by silica, no CI-related lesions were detected at any time postexposure. The results justify the utility of this bioassay as a reliable approach to evaluating the pulmonary toxicity of inhaled particulates.

Administration, Inhalation↗