Biomedical subjects

J F Hansen

Publications and source records attributed to J F Hansen.

At least 91 records · Page 5Linked to original sources

PubMed1991

Calcium antagonists and myocardial infarction.

In vitro and in vivo studies have demonstrated many similarities between the three calcium antagonists verapamil, nifedipine, and diltiazem in relation to protection of the myocardium during hypoxia. Important clinical differences exist between the three drugs when they are used during or after an acute myocardial infarction with the purpose of preventing death and reinfarction. The balance between the negative inotropic and the vasodilator properties and concomitant treatment with beta blockers may explain the results of clinical trials with the three calcium antagonists. Patients not treated with beta blockers. Nifedipine has been demonstrated to be no better than placebo both during and after an acute myocardial infarction. No placebo-controlled studies exist with diltiazem. Verapamil had no effect during the acute phase of a myocardial infarction. After a myocardial infarction, verapamil improved survival and reduced the reinfarction rate, an effect primarily found in patients without heart failure in the coronary care unit. Patients also treated with beta blockers. Nifedipine prevents the development of myocardial infarcts in patients with unstable angina. Diltiazem probably prevents reinfarction in the first two weeks after non-Q-wave infarction. Secondary prevention with diltiazem after an acute myocardial infarction had no overall effect on death or cardiac events (i.e., reinfarction or cardiac death). Subgroup analysis demonstrated in diltiazem-treated patients, compared with placebo-treated patients, a significant reduction of cardiac events in patients without and a significant increase of cardiac events in patients with heart failure. At present no indications exist for nifedipine during or after a myocardial infarction; further studies are needed with diltiazem, and verapamil may be used in secondary prevention of death and reinfarction.

Calcium Channel Blockers↗

PubMed1991

Three-year mortality in patients suspected of acute myocardial infarction with and without confirmed diagnosis. The Danish Study Group on Verapamil in Myocardial Infarction.

The 3-year mortality from day 15 after admission was evaluated prospectively in 11,345 consecutive patients with chest pain suspected of myocardial infarction--4,265 patients with confirmed diagnosis (AMI) and 7,080 patients without confirmed diagnosis (non-AMI), respectively. The mortality rates per year in the first 3 years in the patients with AMI were 14.2%, 6.9%, and 7.6%, and in the non-AMI patients were 8.8%, 5.8%, and 5.5%. The standardized mortality ratio (SMR) correcting for age and sex differences was calculated. SMR is the ratio between the observed mortality in the study population and the expected mortality in an age- and sex-matched subgroup of the general background population. SMR in the first year was 6.7 (95% confidence limits: 6.2 to 7.2) in AMI and 4.7 (4.4 to 5.1) in non-AMI patients. In the second and third years of follow-up, SMR was 3.0 (2.6 to 3.4) and 2.9 (2.5 to 3.4) in AMI and 2.8 (2.5 to 3.1) and 2.4 (2.1 to 2.8) in the non-AMI patients. It is concluded that in the first 3 years the mortality of non-AMI patients is approximately three times higher than in the general population and very close to the late mortality of AMI patients, suggesting that the majority of non-AMI patients are suffering from ischemic heart disease also. Non-AMI patients should consequently be evaluated carefully prior to discharge.

Age Factors↗

PubMed1991

QT interval in 24-hour ambulatory ECG recordings from 60 healthy adult subjects.

QT and RR intervals were measured in 24-hour electrocardiographic (ECG) recordings from 60 healthy subjects randomly selected among participants in the Copenhagen City Heart Study. Five men and five women of each 10-year age group between the ages of 20 and 79 were included. The mean of three consecutive RR and QT intervals was calculated from ECG strips recorded at 1000, 1400, 1800, 2200, 0200, and 0600 hours in each subject. The RR interval varied between 728 ms at 1400 hours and 984 ms at 0600 hours, and the uncorrected QT interval between 358 ms at 1400 hours and 417 ms at 0200 hours. The QT interval corrected for heart rate by Bazett's formula varied between 418 ms at 0600 hours and 428 ms at 1000 hours, and the QT interval corrected by the regression equation of this study varied between 396 ms at 1400 hours and 422 ms at 0200 hours. Multiple regression analysis of uncorrected data yielded a partial regression coefficient for heart rate influence of 0.14. After correction by Bazett's formula, a statistically significant effect of heart rate remained (partial regression coefficient -0.08, t = -9.93, p less than 0.0001). In addition to the influence of heart rate, the analysis revealed a statistically significant effect of hour of day (F = 11.30; DF 5, 286; p less than 0.0001) and gender (F = 6.24; DF 1, 53; p less than 0.05), whereas age in the range of 20-79 years had no significant effect. The QT intervals of this study differed from the values measured in standard ECG recordings but not from those of other Holter studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Development of a short-term inhalation bioassay to assess pulmonary toxicity of inhaled particles: comparisons of pulmonary responses to carbonyl iron and silica.

This paper describes a short-term inhalation bioassay for evaluating the lung toxicity of inhaled particulate materials. To validate the method, rats were exposed for 6 hr or 3 days to various concentrations of either aerosolized alpha-quartz silica or carbonyl iron particles. Cells and fluids from groups of sham- and dust-exposed animals were recovered by bronchoalveolar lavage (BAL). Alkaline phosphatase, lactate dehydrogenase (LDH), and protein values were measured in BAL fluids at several time points postexposure. Cells were identified, counted, and evaluated for viability. Pulmonary macrophages (PM) were cultured and studied for morphology, chemotaxis, and phagocytosis by scanning electron microscopy. The lungs of additional exposed animals were processed for histopathology and transmission electron microscopy. Brief exposures to silica elicited a sustained granulocytic inflammatory response (primarily neutrophils) with concomitant increases in alkaline phosphatase, LDH, and protein in the lavage fluids (p less than 0.05). In addition, PM functional capacity was depressed (p less than 0.05) and histopathologic lesions were observed within 1 month after exposure. In contrast, 6-hr or 3-day exposures to CI produced no cellular, cytotoxic, or alveolar/capillary membrane permeability changes at any time postexposure. PM function was either enhanced or unchanged from controls. These data demonstrate that short-term, high-dose inhalation exposures of silica produce effects similar to those previously observed using intratracheal instillation or chronic inhalation models, and lend support to this method as a reliable short-term bioassay for evaluating the pulmonary toxicity and mechanisms associated with exposures to new and untested materials.

Administration, Inhalation↗

PubMed1991

The self-association of zinc-free human insulin and insulin analogue B13-glutamine.

The self-association of Zn-free human insulin, Zn-free insulin analogue B13-glutamine, 2-Zn insulin and cobalt(III) human insulin in the millimolar concentration range has been investigated by measuring the osmotic pressure at pH 7.5 in 0.05 M NaCl, 25 degrees C. The pH dependence of association has been measured in the pH range 6.8-9. For all insulins, except Zn-free human insulin, the major association state has been found to be the hexamer. Maximal association of hexamer has been observed for Zn-free human insulin at high concentration (2-7 mM) and physiological pH. At concentrations less than 1 mM and pH greater than 7.0, dissociation to a lower state than the hexamer is found. The conclusion has been drawn that, in the absence of metal ions, human insulin and insulin analogue B13-glutamine associate to the hexamer in the physiological pH range at concentrations in the millimolar range.

Humans↗

PubMed1991

Treatment with verapamil after an acute myocardial infarction. Review of the Danish studies on verapamil in myocardial infarction (DAVIT I and II).

The effect of verapamil on death, reinfarctions, and major events, i.e. death or reinfarction after a myocardial infarction has been investigated in 2 Danish double-blind placebo-controlled verapamil infarction trials (DAVIT I and II). DAVIT I was an early intervention trial that demonstrated a statistically nonsignificant reduction in mortality and reinfarction after 6 months of treatment. DAVIT II was a later intervention trial that demonstrated a nonsignificant reduction in the 18-month mortality rate [p = 0.11, hazard ratio 0.80; 95% confidence limits (CL) 0.61 to 1.05], a significant reduction in the reinfarction rate (p = 0.04, hazard ratio 0.77; CL 0.58 to 1.03), and in the major event rate (p = 0.03, hazard ratio 0.80; CL 0.64 to 0.99) in the verapamil group compared with the placebo group. In patients without heart failure in the coronary care unit, a statistically significant reduction in the 18-month mortality rate (p = 0.02, hazard ratio 0.64; CL 0.44 to 0.94), the reinfarction rate (p = 0.02, hazard ratio 0.67; CL 0.46 to 0.97), and the major event rate (p = 0.01, hazard ratio 0.70; CL 0.52 to 0.93) was observed in the verapamil group compared with the placebo group. No significant differences were found in patients with heart failure. Meta-analyses of DAVIT I (for patients alive at day 8) and DAVIT II showed a statistically significant reduction in the odds ratio of mortality (22%), reinfarctions (27%), and the major event rate (21%) in verapamil-treated patients. It is concluded that long term treatment with verapamil after an acute myocardial infarction is associated with a significant reduction in overall mortality, major events, and reinfarctions, with the greatest effect in patients without heart failure.

Angina Pectoris↗

PubMed1991

Treatment with verapamil during and after an acute myocardial infarction: a review based on the Danish Verapamil Infarction Trials I and II. The Danish Study Group on Verapamil in Myocardial Infarction.

The effect of verapamil on death and reinfarction after an acute myocardial infarction was studied in two double-blind, randomized, placebo-controlled multicenter trials, the Danish Verapamil Infarction Trials I and II (DAVIT I and II). The studies demonstrated that verapamil 360 mg/day from the 2nd week after an acute myocardial infarction, prevented death and reinfarction. Meta-analyses of the results of DAVITs I and II resulted in a reduction of pooled ratios of 22% (95% confidence limits 1-37, p = 0.04) for death, 21% (5-35, p = 0.02) for first major events (first reinfarction or death), and 27% (6-43, p = 0.02) for first reinfarctions. The effect of verapamil was to prevent myocardial ischemia and reduce sudden death and reinfarction. It is concluded that long-term treatment with verapamil after an acute myocardial infarction may be recommended with the object of reducing overall mortality, major events and reinfarction.

Arrhythmias, Cardiac↗

PubMed1991

Effect of verapamil on ischemia and ventricular arrhythmias after an acute myocardial infarction: prognostic implications. The Danish Verapamil Infarction Trial II Study Group.

This article is a review of presented subsets of the Danish Verapamil Infarction Trial II (DAVIT II) regarding the effect of verapamil on postinfarction ischemia, ventricular arrhythmias, and heart rate (HR), and the prognostic implications of these findings. Patients underwent Holter monitoring for 24-48 h at 1 week, i.e., before randomization to long-term treatment with placebo or verapamil, and after 1 month and about 1 year of study treatment. Ischemia: 18% of the patients had transient ST-segment deviation before randomization; 24% of the placebo- and 8% of the verapamil-treated patients (p = 0.04) showed ischemia after 1 month; and after 1 year, the figures were 26 and 4%, respectively (p = 0.02). The 18-month major event rate, i.e., first reinfarction or death, in patients with ischemia before randomization were 40 and 23.8% in patients without ischemia (p = 0.06). Arrhythmias: In the placebo group the prevalence and incidence of many ventricular ectopic beats (VEBs), i.e., more than 10 VEBs/h, increased significantly during the first years after infarction; this was not the case in the verapamil patients group. The mean HR was significantly reduced by verapamil treatment after 1 month and after 16 months of treatment. Multivariate analysis demonstrated the presence of more than 10 VEBs/h only early (i.e., 1 week) but not late (i.e., 1 month) after infarction, to be an independent predictor of major events during 18 months' follow-up observation. A HR above 80 beats/min independently predicted major events when appearing both early and late after infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1990

Propafenone versus quinidine slow-release for the treatment of chronic ventricular arrhythmias.

The efficacy and side-effects of oral propafenone 300 mg b.i.d. were compared to those of quinidine slow-release 800 mg b.i.d. in a randomized double-blind placebo controlled cross-over study in 12 patients with symptomatic premature ventricular complexes (PVCs). Furthermore during steady-state the plasma levels of propafenone and quinidine were measured repeatedly over an 8-hour period and correlated to the numbers of PVCs. In 6 patients both drugs reduced PVCs by 80%. In 2 patients this effect was obtained by propafenone and not by quinidine, while the reverse was found in another 2 patients. In 2 patients neither of the drugs was able to reduce PVCs by 80%. During treatment with quinidine 4 patients experienced diarrhoea and 1 patient suffered headaches taking propafenone. The plasma levels showed great variation. No correlation between the plasma levels expressed as area under the concentration-time curve and the reduction of PVCs was found.

Adult↗

PubMed1989

Spectroscopic signatures of the T to R conformational transition in the insulin hexamer.

The cobalt(II)-substituted human insulin hexamer has been shown to undergo the phenol-induced T6 to R6 structural transition in solution. The accompanying octahedral to tetrahedral change in ligand field geometry of the cobalt ions results in dramatic changes in the visible region of the electronic spectrum and thus represents a useful spectroscopic method for studying the T to R transition. Changes in the Co2+ spectral envelope show that the aqua ligand associated with each tetrahedral Co2+ center can be replaced by SCN-, CN-, OCN-, N3-, Cl-, and NO2-. 19F NMR experiments show that the binding of m-trifluorocresol stabilizes the R6 state of zinc insulin. The chemical shift and line broadening of the CF3 singlet, which occur due to binding, provide a useful probe of the T6 to R6 transition. Due to the appearance of new resonances in the aromatic region, the 500 MHz 1H NMR spectrum of the phenol-induced R6 hexamer is readily distinguishable from that of the T6 form. 1H NMR studies show that phenol induces the T6 to R6 transition, both in the (GlnB13)6(Zn2+)2 hexamer and in the metal-free GlnB13 species; we conclude that metal binding is not a prerequisite for formation of the R state in this mutant.

Insulin↗

PubMed1989

[Treatment of acute myocardial infarction--an elucidative report].

The present-day optimal treatment of patients with acute myocardial infarction (AMI) is reviewed. The prehospital phase should be as brief as possible. Emergency observation and treatment in hospital should be initiated without delay. Schematic stages for mobilization have been discarded and free mobilization is recommended. Routine acute intervention with thrombolysis is recommended for patients in whom symptoms have been present for 6-12 hours and treatment with Aspirin is recommended. Beta-blocking agents are recommended for patients with increased risk after discharge. Treatment of ventricular and supraventricular arrhythmias, block and cardiac failure are reviewed in detail. Patients without complications should be monitored for three to five days and may be discharged after seven to ten days. Exercise ECG should be carried out at discharge to assess the working capacity, ischaemia and subjective reaction. The importance of good patient information is emphasized. Cessation of smoking, control of lipids and blood pressure are important as secondary interventions. As far as possible, outpatient control should be offered after discharge. The criteria for referral to specialized cardiological departments are established both for emergency and elective referral. Patients under the age of 70 years with high risk for repeated AMI or death after discharge (with residual ischaemia) should possibly be referred for coronary arteriography.

Adrenergic beta-Antagonists↗

PubMed1989

Circadian variation in the pharmacokinetics of verapamil.

Circadian variation in the metabolism of verapamil was investigated in 10 patients with stable angina pectoris during treatment with sustained-release verapamil 360 mg at 08.00 h or 22.0 h. No major difference in exercise parameters was found. During the evening dosage schedule a significantly greater bioavailability (AUC) and a prolonged time to peak concentration was found. During the night (24.00 h-06.00 h) the half-life of verapamil was significantly longer than during the day (16.00 h-22.00 h). These differences in pharmacokinetics may be due to reduced hepatic blood flow at night or to circadian variation in hepatic microsomal metabolism.

Angina Pectoris↗

PubMed1989

Sustained-release and instant-release verapamil in treatment of angina pectoris.

The efficacy of a sustained-release preparation of verapamil (verapamil-SR) has been compared with that of a conventional instant-release formulation (verapamil-IR) in 10 patients with stable angina pectoris treated for 3 weeks with both preparations. The diurnal serum concentrations of verapamil and norverapamil did not differ significantly during treatment with verapamil-IR 120 mg t.i.d. and verapamil-SR 360 mg once daily, but verapamil-SR 240 mg produced significantly lower serum concentrations. The differences did not affect the exercise capacity or the occurrence of ST-segment depression during maximal exercise. Verapamil-SR was well tolerated. A multiple instant-release dosage regime can now be replaced by once daily administration of the sustained-release preparation.

Angina Pectoris↗

PubMed1989

Coronary collateral circulation: clinical significance and influence on survival in patients with coronary artery occlusion.

In a consecutive series of 96 patients with coronary artery occlusion, 67 had good and 29 had no or poor collateral circulation. Patients with good collaterals had the severest degree of coronary artery disease. Good collaterals are associated with a higher incidence of angina pectoris and normal electrocardiogram and with lower incidence of Q-waves, positive exercise tests, heart failure, previous myocardial infarction, and dyskinesia at ventriculography. Survival rates after 10 years were (1) 51.5% with good and 34.5% with poor collaterals (p less than 0.1), (2) 59.4% with angina pectoris and good collaterals and 41.2% with angina pectoris and poor collaterals (p less than 0.05), (3) 64.8% without and 24.4% with heart failure and good collaterals (p less than 0.001), and (4) 58.3% without and 16.1% with heart failure and poor collaterals (p less than 0.01). Good collaterals protect the myocardium by prevention of acute myocardial infarction and heart failure and thus improve survival.

Angina Pectoris↗

PubMed1988

Monomeric insulins obtained by protein engineering and their medical implications.

The use of insulin as an injected therapeutic agent for the treatment of diabetes has been one of the outstanding successes of modern medicine. The therapy has, however, had its associated problems, not least because injection of insulin does not lead to normal diurnal concentrations of insulin in the blood. This is especially true at meal times when absorption from subcutaneous tissue is too slow to mimic the normal rapid increments of insulin in the blood. In the neutral solutions used for therapy, insulin is mostly assembled as zinc-containing hexamers and this self-association, which under normal physiological circumstances functions to facilitate proinsulin transport, conversion and intracellular storage, may limit the rate of absorption. We now report that it is possible, by single amino-acid substitutions, to make insulins which are essentially monomeric at pharmaceutical concentrations (0.6 mM) and which have largely preserved their biological activity. These monomeric insulins are absorbed two to three times faster after subcutaneous injection than the present rapid-acting insulins. They are therefore capable of giving diabetic patients a more physiological plasma insulin profile at the time of meal consumption.

Animals↗

PubMed1988

Independent prognostic risk factors for patients referred because of suspected acute myocardial infarction without confirmed diagnosis. Prognosis after discharge in relation to medical history and non-invasive investigations.

Variables associated with risk of cardiac events, i.e. acute myocardial infarction (AMI) or cardiac death after discharge, were studied in patients who had been referred to coronary care units because of suspected AMI due to chest pain, but in whom this was not confirmed. The patients were all under 76 years of age, and were followed from 12 to 24 months, median 14 months. The estimated percentage without a cardiac event in 257 patients after one year was 91.3. On the basis of prognostic and clinical importance the analyzed variables included selected aspects of the medical history, electrocardiogram on admission in all 257 patients, subsequent electrocardiogram at rest, exercise test, thallium scintigraphy, chest X-ray, echocardiography, systolic time intervals and Holter monitoring when possible in 217 patients. Multivariate analysis identified combined electrocardiogram at rest and during exercise as the only variable with independent prognostic information. The presence of ST segment deviation, Q-wave, negative T-wave or intraventricular block in the electrocardiogram at rest or an abnormal ST segment response during exercise, increased the hazard of a cardiac event by a factor of 11.8. It is concluded that patients without confirmed AMI are at risk following discharge. These patients should undergo an exercise test and those with an abnormal electrocardiogram at rest and/or during exercise should be followed closely after discharge.

Adult↗

PubMed1988

Significance of ventricular ectopic activity in the early recovery phase of acute myocardial infarction.

Holter monitoring of 51 patients on the 4th to 6th day after acute myocardial infarction (AMI) disclosed complex ventricular ectopic beats in 17 (35%), nine of whom (53%) died in the following 26 months. Of the remaining patients with no or only non-complex ectopic beats, five (15%) died. The difference was significant using Gehan's test of censored data (p less than 0.01). Multivariate analysis demonstrated a significant increase of death risk associated with complex ventricular ectopic beats as well as with heart failure (relative risk 3.6 and 5.9, respectively). Age, gender, number of ventricular ectopic beats, cardiac enlargement on X-ray and angina pectoris had no significant effect on mortality. The prevalence of ventricular ectopy was 84% (n = 43) irrespective of age and sex and equal to the finding in the late hospital phase reported by other investigators, and in healthy subjects. Complex ventricular ectopic beats appeared in 35% (n = 17). The prevalence increased significantly with age and was significantly higher in post-infarction patients (38%) than in healthy individuals (8%). The present results indicate that a subgroup containing most of the high-risk patients may be identified early after AMI by detecting complex premature ventricular beats in continuous electrocardiographic recordings.

Adult↗

PubMed1988

Prognosis and thallium-201 scintigraphy in patients admitted with chest pain without confirmed acute myocardial infarction.

Exercise and rest thallium scintigraphy and exercise electrocardiography were performed after discharge in 158 patients aged less than 76 years admitted with chest pain in whom a suspected diagnosis of acute myocardial infarction had not been confirmed. During a follow up of 12-24 months (median 14 months) there were 10 cardiac events--that is, non-fatal acute myocardial infarction or cardiac deaths. Transient thallium defects and abnormal ST response (that is ST segment deviation or uninterpretable ST segment) during exercise were correlated significantly with an unfavourable prognosis. One hundred and four patients with neither of these characteristics were at lower risk of a cardiac event than the 19 patients with both of these characteristics. The percentages of patients in these two groups without a cardiac event after one year were 98.1 and 78.8 respectively. Thallium scintigraphy, alone or in combination with exercise electrocardiography, can be used to identify groups at high and low risk of future cardiac events, in patients with chest pain in whom acute myocardial infarction is suspected but not found.

Chest Pain↗