Biomedical subjects

J F Hansen

Publications and source records attributed to J F Hansen.

At least 55 records · Page 3Linked to original sources

PubMed1997

Inhalation of high concentrations of low toxicity dusts in rats results in impaired pulmonary clearance mechanisms and persistent inflammation.

This study was carried out to assess the time course of pulmonary clearance impairment and persistence of inflammation following high-dose inhalation exposures to titanium dioxide (TiO2) or carbonyl iron (CI) particles. Male rats were exposed to air, TiO2 or CI particles 6 hr/day, 5 days/week, for 4 weeks at concentrations of 5, 50, and 250 mg/m3 and evaluated at selected intervals through 6 months postexposure. Indices of pulmonary inflammation as well as alveolar macrophage clearance functions (i.e., morphology, in vivo and in vitro phagocytosis, and chemotaxis), cell proliferation, and histopathology endpoints were measured at several postexposure time periods through 6 months. In addition, amounts of TiO2 or CI in lungs and tracheobronchial lymph nodes were measured to allow an evaluation of particle clearance and translocation patterns. Four-week exposures to TiO2 or CI particles at concentrations of 250 mg/m3 resulted in lung burdens of 12 mg titanium and 17 mg iron, respectively, with particle retention half-times ranging from 68 days for 5 mg/m3 TiO2 to approximately 330 days for 250 mg/m3. The impact of this TiO2 dust load and similar lung burdens of CI particles produced a sustained pulmonary inflammatory response measured through a period of 3-6 months postexposure concomitant with increases in BrdU cell labeling of terminal airway and pulmonary parenchymal cells. The impairment of particle clearance mechanisms was accounted for by deficits in in vitro phagocytic and chemotactic potential of alveolar macrophages recovered from the lungs of high-dose, TiO2- or CI-exposed rats. Free granular pigment (TiO2 or CI) was present on the hypertrophic mucosal surfaces of bronchioles and bronchi, and particle-laden macrophages, found individually, were numerous throughout alveoli and within lymphoid tissues immediately after exposure. Aggregates of particle-laden macrophages were present within alveoli and alveolar ducts from 1 week postexposure through the entire 6-month recovery period. Macrophage accumulations increased in size and number from 1 week through 1 month postexposure and then appeared to remain constant through the remaining 5-month postexposure period. Minimal cellular hypertrophy and hyperplasia were evident at alveolar duct bifurcations adjacent to macrophage aggregates, and this effect was most prominent at 3 to 6 months postexposure. The results of this study clearly demonstrate that exposure to high dust concentrations of two different innocuous particle types produced sustained pulmonary inflammation, enhanced proliferation of pulmonary cells, impairment of particle clearance, deficits in macrophage function, and the appearance of macrophage aggregates at sites of particle deposition. In addition, the mass deposition rate determination appears to be a less sensitive indicator of "overload" when compared to biomarkers of pulmonary toxicity, such as macrophage function and cellular inflammation and proliferation indices.

Administration, Inhalation↗

PubMed1997

Treatment with verapamil and trandolapril in patients with congestive heart failure and angina pectoris or myocardial infarction. The DAVIT Study Group. Danish Verapamil Infarction Trial.

In a double-blind, randomized trial in a consecutive group of postinfarct patients in treatment with diuretic agents for congestive heart failure, the 3 month rate of cardiac events (i.e., death, repeat infarction, unstable angina pectoris, or repeat admission because of heart failure) was 14% in patients treated with verapamil and trandolapril and 35% in patients treated with trandolapril (p = 0.01). In another study of patients with angina pectoris and left ventricular ejection fraction less than 40%, trandolapril plus verapamil improved exercise duration and left ventricular ejection fraction. These findings indicate that combined treatment with verapamil and trandolapril may be beneficial in patients with congestive heart failure.

Adult↗

PubMed1997

Effects of amlodipine and isosorbide dinitrate on exercise-induced and ambulatory ischemia in patients with chronic stable angina pectoris.

This study was designed to compare once-daily administration of 5-10 mg amlodipine with two daily doses of 40 mg sustained-release isosorbide dinitrate in 59 patients with stable angina using a randomized, double-blind, crossover study design. Anginal episodes, nitroglycerin consumption, and possible adverse events were recorded in a diary. A maximal symptom-limited bicycle exercise test and 48-hour ambulatory ECG monitoring were performed at baseline and at the end of each 5-week period of therapy. Exercise time, time to angina, time to ST depression, and maximal ST depression were measured during exercise. During ambulatory monitoring, the number of ischemic episodes and the duration per hour of ST depression were assessed. Amlodipine significantly reduced anginal episodes (P < 0.001) when compared with isosorbide dinitrate. Furthermore, amlodipine prolonged time to ST depression (P < 0.001) and time to angina (P < 0.05) when compared with isosorbide dinitrate. The number and duration of ischemic episodes during ambulatory monitoring were significantly reduced with amlodipine when compared with baseline values (P < 0.05), whereas no differences were found between isosorbide dinitrate and baseline. Adverse events were reported more frequently with isosorbide dinitrate than with amlodipine (P < 0.02). Amlodipine appears to be more effective and tolerable than sustained-release isosorbide dinitrate as monotherapy for chronic stable angina.

Adult↗

PubMed1997

How European cardiologists perceive the role of calcium antagonists in follow-up after myocardial infarction.

About one hundred European cardiologists discussed the role of calcium antagonists in the follow-up management of myocardial infarction. beta-blockers are the treatment of choice. Where these are contra-indicated or otherwise unsuitable, many clinicians would use a non-dihydropyridine calcium antagonist alone or in combination with an ACE inhibitor. There is broad agreement that calcium antagonists should not be used in patients with concomitant left ventricular failure. Cholesterol estimation in post-infarction patients is essential.

Adrenergic beta-Antagonists↗

PubMed1997

Treatment with verapamil and trandolapril in patients with congestive heart failure and myocardial infarction. The Danish Verapamil Infarction Trial (DAVIT Study Group).

UNLABELLED: EFFECTS OF VERAPAMIL AND TRANDOLAPRIL: Progression of heart failure, sudden death and death from re-infarction are the major cause of the increased mortality in postinfarct patients with congestive heart failure. Angiotensin converting enzyme (ACE) inhibitors such as trandolapril can prevent the progression of heart failure and thus improve survival. The calcium antagonist verapamil has been shown to prevent sudden death and re-infarction in postinfarct patients without congestive heart failure. HYPOTHESIS: The Danish Verapamil Infarction Trial (DAVIT) study group hypothesized the combined treatment with trandolapril and verapamil might prevent cardiac events in postinfarct patients with coronary heart disease. The first double-blind randomized trial included 100 patients and supported this hypothesis, as the cardiac event rate was significantly lower after 3 months in patients treated with the combination than in those treated with trandolapril alone (14 versus 35%, respectively; P = 0.01, hazard ratio 0.35, 95% confidence interval 0.15-0.85).

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1996

[Prognostic values of echocardiography compared with clinical variables in suspected heart disease. Multivariate analysis of long-term prognosprognosis in 456 patients].

The aim of the study was to evaluate the prognostic significance of clinical and echocardiographic data in patients referred for echocardiography in a retrospective analysis. Four hundred and fifty-six patients from a district hospital were studied. Survival after three years was 64%. Multivariate analysis identified five factors with independent prognostic information (relative risks of death are shown in brackets): left ventricular wall motion index (WMI) < or = 1.2 by echocardiography (2.5), status as in-patient (2.1), age > 65 years (1.7), clinical heart failure (1.9) and atrial fibrillation (1.5). When information on age, hospitalisation status, heart failure and heart rhythm had already been entered in the Cox model, echocardiographic results such as decreased WMI and dilated right ventricle still gave further prognostic information. We conclude that among conventional clinical and echocardiographic data WMI was the strongest predictor of long-term survival, and, despite prior knowledge of major clinical features, echocardiography provided further prognostic information.

Adult↗

PubMed1996

Sex related differences in short and long-term prognosis after acute myocardial infarction: 10 year follow up of 3073 patients in database of first Danish Verapamil Infarction Trial.

OBJECTIVE: To re-examine the prevailing hypothesis that women fare worse than men after acute myocardial infarction. DESIGN: 10 year follow up of all patients with confirmed acute myocardial infarction registered in the database of the Danish verapamil infarction trial in 1979-81. SETTING: 16 coronary care units, covering a fifth of the total Danish population. PATIENTS: 3073 consecutive patients with acute myocardial infarction, 738 (24%) women and 2335 (76%) men. MAIN OUTCOME MEASURES: Early mortality (before day 15). For patients alive on day 15: mortality, cause of death, admission with recurrent infarction, and mortality after reinfarction. RESULTS: Early mortality increased significantly with age (P < 0.0001) but was not significantly related to sex, with a 15 day mortality of 17% in women and 16% in men. Adjustment for age and sex simultaneously revealed a significant interaction (P = 0.02) between these variables, with a greater increase with age in early mortality for men than for women (early mortality was equal for the two sexes at age 64 years). Ten year mortality in patients alive on day 15 was 58.8%. The overall age adjusted hazard ratio (95% confidence interval) for women versus men was 0.90 (0.80 to 1.01); 0.90 (0.78 to 1.04) for 10 year reinfarction (48.8%); and 0.98 (0.82 to 1.16) for 10 year mortality after reinfarction (82.3%). No difference in cause of death was found between the sexes. With a follow up of up to 10 years for patients alive on day 15 mortality, rate of reinfarction, and mortality after reinfarction increased with increasing age (P < 0.0001). CONCLUSION: Sex by itself is not a risk factor after acute myocardial infarction.

Aged↗

PubMed1996

Verapamil and angiotensin-converting enzyme inhibitors in patients with coronary artery disease and reduced left ventricular ejection fraction.

Verapamil is effective as antianginal medication but contraindicated in patients with congestive heart failure. Angiotensin-converting enzyme (ACE) inhibitors improve survival in patients with congestive heart failure but have limited effect on patients with angina pectoris. No studies have been published on the combined treatment with verapamil and ACE inhibitors in patients with stable angina pectoris and left ventricular dysfunction. We performed an open study in 14 patients with angina pectoris and ejection fraction < 40%. The patients received verapamil 180 mg and trandolapril 2 mg twice daily for 3 months. We found a significant increase in ejection fraction from 28 +/- 6 to 35 +/- 11 (p < 0.03), wall motion index from 1.0 +/- 0.3 to 1.2 +/- 0.3 (p < 0.03), exercise duration from 6.9 +/- 2.5 to 7.7 +/- 2.9 minutes (p < 0.01), and ratio of exercise to rest rate-pressure product from 2.2 +/- 0.4 to 2.5 +/- 0.6 (p < 0.02). Use of nitroglycerin and number of angina pectoris attacks were both significantly reduced after 3 months of treatment. These findings support the hypothesis that the combination of verapamil and trandolapril is useful in patients with attenuated left ventricular function and angina pectoris.

Aged↗

PubMed1995

[10-year mortality of patients admitted to coronary units with or without confirmed diagnosis of myocardial infarction. A relation to anamnesis and diagnosis at discharge].

The ten-year mortality in patients with suspected myocardial infarction with (AMI) and without (non-AMI) confirmed diagnosis was evaluated in 1897 non-AMI patients and 1401 AMI patients who were consecutively admitted to hospital during The Danish Verapamil Infarction Study. The following risk factors contained 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. When the diagnosis at discharge for non-AMI patients was included in the Cox-analysis, only the diagnoses of bronchopneumonia, musculoskeletal disorders and observation only of added 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 the medical history and should be carefully evaluated regarding coronary artery disease at the time of discharge in order to improve the risk stratification, treatment and prognosis.

Adult↗

PubMed1995

Effect of verapamil on the prognosis of patients with early postinfarction electrical or mechanical complications. The Danish Verapamil Infarction Trial II (DAVIT II).

The Danish Verapamil Infarction Trial II (DAVIT II) demonstrated from the second postinfarction week, that long term treatment with verapamil significantly improved reinfarction free survival after an acute myocardial infarction (AMI). The present post hoc analysis of DAVIT II was undertaken with the purpose of evaluating the effect of treatment with verapamil in patients with early electrical complications, i.e. ventricular or atrial fibrillation, ventricular tachycardia, or second or third degree atrioventricular block, with or without mechanical complication, i.e. heart failure, during the first post-AMI week. In the placebo group, the 18-month mortality rate was lowest (9.5%) in patients without electrical or mechanical complications, highest (24.6%) in patients with electrical events only, and in-between (17.5%) in patients with mechanical problems regardless of presence of electrical complications. Verapamil significantly reduced the 18-month mortality rate in patients with early electrical without mechanical complications (60% reduction, P = 0.02), and in patients without mechanical complications (35% reduction, P = 0.02). Verapamil did not change the mortality rate in patients with mechanical complications.

Aged↗

PubMed1995

Two-year inhalation toxicity study in rats with hydrochlorofluorocarbon 123.

The potential chronic toxicity and oncogenicity of hydrochlorofluorocarbon 123 (HCFC-123) was evaluated by exposing male and female rats to 0, 300, 1000, or 5000 ppm HCFC-123 for 6 hr/day, 5 days/week, for 2 years. Clinical pathology was evaluated at 6, 12, 18, and 24 months. An interim termination and measurements of hepatic cell proliferation and beta-oxidation activity were conducted at 12 months. The terminal euthanization occurred at 24 months. Males and females exposed to 5000 ppm and females exposed to 300 or 1000 ppm had lower body weights and body weight gains. Serum triglyceride and glucose concentrations were significantly decreased at all exposure concentrations in both sexes. Serum cholesterol was also lower in 300, 1000, and 5000 ppm females and in 5000 ppm males. Alterations in serum protein concentrations occurred at 300, 1000, and 5000 ppm. Survival was higher in 1000 and 5000 ppm males and females. At 24 months, increased relative liver weight occurred in 5000 ppm males, and decreased absolute kidney weight occurred in 5000 ppm males and in 1000 and 5000 ppm females. Benign hepatocellular adenomas were increased in 5000 ppm males and in all test groups of females. Hepatic cholangiofibromas were also increased in 5000 ppm females. Pancreatic acinar cell adenomas were increased in all test groups of males, and acinar cell hyperplasia was increased in the 1000 and 5000 ppm males and females. Benign testicular interstitial adenomas and focal interstitial cell hyperplasia were also increased in all male test groups compared to controls. Diffuse retinal atrophy was increased in all male and female test groups, but it was considered to be an indirect compound-related effect. Hepatic beta-oxidation activity (peroxisome proliferation) was higher in 300, 1000 and 5000 ppm males and 1000 and 5000 ppm females. Compound-related differences in the rate of hepatic cell proliferation were not observed at any exposure concentration. Decreased incidences of a variety of age-related lesions occurred at 1000 and 5000 ppm.

Administration, Inhalation↗

PubMed1995

ACE inhibitors and calcium antagonists in the treatment of congestive heart failure.

The increased mortality after myocardial infarction is related to the risk of reinfarction, sudden death, and the development and progression of heart failure; in congestive heart failure it is due to the progression of heart failure and sudden death. ACE inhibitors have been proven to prevent cardiovascular events, especially the progression of heart failure, in postinfarct patients with reduced ejection fraction and heart failure in the SAVE and AIRE trials. In patients with congestive heart failure, ACE inhibitor treatment has prevented cardiovascular death and reduced morbidity due to progressive heart failure in the SOLVD trials. In post-myocardial infarction patients, the calcium antagonist nifedipine did not affect mortality or morbidity; diltiazem improved prognosis in patients without congestive heart failure and in patients with non-Q-wave infarction; and verapamil improved prognosis by prevention of reinfarction and sudden death. Combination treatment with both verapamil, which has pronounced antiischemic properties and prevents sudden death and reinfarction, and an ACE inhibitor, which prevents the progression of heart failure, is a possibility for future cardiovascular therapy that should be evaluated.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1995

(-)-anipamil retards atherosclerosis in Watanabe heritable hyperlipidemic rabbits.

Calcium antagonists have been reported to limit atherosclerosis in cholesterol fed rabbits. The purpose of this study was to examine the effect of the calcium antagonist (-)-anipamil on the spontaneous development of atherosclerosis in homozygote WHHL rabbits. From the age of 7 weeks, three groups of rabbits received 0 (control, n = 11), 1 mg/kg body weight (n = 11), or 10 mg/kg body weight (n = 12) of (-)-anipamil for 17 weeks. Serum cholesterol at start of the investigation was 18.8 +/- 1.2 (mean +/- SEM), 20.5 +/- 1.8, and 19.5 +/- 0.8 mM, respectively, in the three groups. No significant differences were found in serum lipids (i.e., VLDL, IDL, LDL, HDL) in the study period among the three groups. Plasma anipamil at the end of the study was 0.23 +/- 6, and 202 +/- 19 ng/ml, respectively, in the three treatment groups. The degree of atherosclerosis in the abdominal aorta was significantly lower (p < 0.02) in the 10 mg/kg body weight (-)-anipamil group compared with the two other groups. No significant difference was found in the thoracic aorta. It is concluded that (-)-anipamil retards development of atherosclerosis in the abdominal aorta in WHHL rabbits.

Animals↗

PubMed1995

Short- and long-term prognostic implications of in-hospital postinfarction arrhythmias. DAVIT II Study Group.

The purpose of the present study was to evaluate, in patients surviving the first postinfarction week, the short- and long-term prognostic implications of arrhythmias, and their relation to easily obtained anamnestic and clinical parameters presented during hospitalisation. The study consisted of 897 placebo-treated patients of the Danish Verapamil Infarction Trial II (DAVIT II). In patients with and without supraventricular tachycardia mortality within 2 months was 9.2 and 3.7% (p = 0.004), respectively. By multivariate analysis supraventricular tachycardia independently predicted mortality within 2 months. Mortality within 5 years was predicted by the presence of supraventricular tachycardia, atrial fibrillation, advanced atrioventricular block, sinoatrial block, and of the combined arrhythmic parameter, i.e. ventricular and/or atrial fibrillation and/or advanced atrioventricular block. When easily obtained and assessed anamnestic and clinical parameters were included in a multivariate analysis, the presence of supraventricular tachycardia alone gave independent prognostic information on long-term mortality.

Aged↗

PubMed1994

Ten year mortality in patients with suspected acute myocardial infarction.

OBJECTIVE: To describe the 10 year mortality in patients with suspected acute myocardial infarction. DESIGN: Follow up of all patients below 76 years of age admitted with acute chest pain to 16 coronary care units participating in the Danish verapamil infarction trial in 1979-81. SUBJECTS: Of the 5993 patients included, 2586 had definite infarction, 402 had probable infarction, and 3005 did not have infarction. MAIN OUTCOME MEASURES: Death and cause of death. Standardised mortality ratio (observed mortality/expected mortality in background population). RESULTS: The estimated 10 year mortalities were 58.8%, 55.5%, and 42.8% in patients with definite, probable, and no infarction, respectively (P < 0.0001). Stratified Cox's analysis identified a hazard ratio for mortality of 1.25 (95% confidence interval 1.08 to 1.44) for probable infarction compared with no infarction and of 1.15 (1.00 to 1.32) for definite compared with probable infarction. The standardised mortality ratio in the first year was 7.1 (6.5 to 7.8) for definite infarction, 5.0 (3.6 to 6.3) for probable infarction, and 4.7 (4.2 to 5.2) for no infarction. From the second year and onwards the annual standardised mortality ratio in the three groups did not differ significantly. Cardiac causes of deaths were recorded in 89%, 84%, and 71% of the deaths in patients with definite, probable, and no infarction, respectively. CONCLUSIONS: The 10 year mortality of patients with and without infarction is significantly higher than in the background population. Most deaths are caused by coronary heart disease, and these patients should consequently be further evaluated at the time of discharge and followed up closely.

Adult↗

PubMed1994

Effect of verapamil on arrhythmias and heart rate during 16 months following an acute myocardial infarction. The Danish Study Group on Verapamil in Myocardial Infarction.

The present study was a prospectively planned subset of the postinfarction, double blind, randomized, multicenter, placebo controlled trial of verapamil, DAVIT II. Patients had 24 hours of Holter monitoring before randomization, i.e., second week after infarction (placebo, n = 122; verapamil, n = 128), after 1 month (placebo, n = 108; verapamil, n = 94) and after 16 months (placebo, n = 75; verapamil, n = 63) of treatment. The purpose was to evaluate the effect of verapamil on the prevalence and changes over time of arrhythmias and heart rate. In patients monitored twice, a significant increase of average ventricular premature complexes (VPC) per hour from before to 1 month (p = 0.0007) and 16 months (p = 0.02) after was demonstrated in the placebo group, and from before to 1 months (p = 0.01) after in the verapamil group. Average VPC/hr did not change from 1 to 16 months of treatment. A significant increment of > 10 VPC/hr was found after 1 (p = 0.03) and 16 months (p = 0.05) compared to prerandomization in the placebo, but not in the verapamil group. A significant increase of supraventricular arrhythmias after 1 month compared with prerandomization was found in the placebo group (p = 0.003) but not in the verapamil group. The prevalence of VPC and supraventricular tachycardia was significantly lower in the verapamil compared with the placebo group after 1 month of treatment. At 16 months no significant difference was found between the two groups. The 24 hour mean heart rate was significantly lower, 3 beats/min, in the verapamil compared with placebo after 1 and 16 months of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1994

Review of postinfarct treatment with verapamil: combined experience of early and late intervention studies with verapamil in patients with acute myocardial infarction. Danish Study Group on Verapamil in Myocardial Infarction.

An overview of the published studies on the use of verapamil during and after an acute myocardial infarction is presented. Meta-analyses of the two small early intervention trials, one early intervention trial followed by a 6-month treatment period (The Danish Verapamil Infarction Trial I, DAVIT I) and one late intervention trial (DAVIT II), demonstrated a 17-20% statistically nonsignificant reduction of mortality, first reinfarctions, and first major events. In DAVIT II was found a statistically significant 20% reduction of first major events in verapamil-treated patients. In patients without heart failure during the acute event mortality, first reinfarctions and first major events were significantly reduced by 30-36% in verapamil-treated patients. No difference was found in patients treated for heart failure in the coronary care unit. A meta-analysis based on patients included in DAVIT I alive day 8 and all patients included in DAVIT II demonstrated a statistically significant 21-26% reduction of mortality, first reinfarctions, and first major events.

Denmark↗

PubMed1994

Evaluation of a method used to test for potential toxicity of carpet emissions.

After a private testing laboratory had reported mortality, neurotoxicity, and respiratory irritation in mice exposed to emissions from heated carpet in a modified application of the sensory irritation test (ASTM E981-84), the studies reported in this paper were conducted to evaluate the method used in testing for carpet toxicity and to see if the reported findings were reproducible. Mice were exposed head-only to offgasses generated by heating carpet (AT #3) to temperatures that ranged from 37 to 70 degrees C. Control mice were simultaneously exposed to heated air. The animals were evaluated for mortality, clinical signs and respiratory irritation. Neurotoxicity was evaluated using functional observational battery and motor activity monitoring. Pathological evaluations of organs and tissues, including the nervous system, were also conducted. The carpet samples heated to higher temperatures produced greater concentrations of total volatile organic compounds than those heated to 37 degrees C. Both carpet-exposed and control mice displayed some effects, such as body weight loss, mortality and pathological lesions, that were due to the exposure system. There was no mortality or neurotoxicity, nor were there clinical signs or pathological lesions as a result of carpet exposures. Mice exposed to carpet heated to 70 degrees C had slightly decreased respiratory rates and an increased incidence of breathing patterns indicative of sensory irritation. Therefore, none of the results reported by the private testing laboratory could be reproduced when this carpet was heated to temperatures below 70 degrees C, and slight sensory irritation was the only effect observed at the 70 degrees C test conditions. Effects from the exposure system itself made interpretation of results difficult, and concurrent controls were considered essential for interpretation of data.

Air Pollution, Indoor↗