Impaired glucose tolerance and diabetes mellitus in elderly subjects.

In a 10-yr prospective population study 406 subjects who were 70 yr old received an oral glucose tolerance test. Of these subjects 169 were retested at 80. Three sets of diagnostic criteria were evaluated, of which the WHO criteria are recommended for screening studies in this age group. The prevalences of diabetes mellitus (DM) and impaired glucose tolerance (IGT) according to the latter criteria were 10% and 26% at 70 and 12% and 35% at 80 in men and women. Excess 10-yr mortality was seen in both sexes when DM existed at 70, and in men also when IGT existed at this age. The excess mortality in men could solely--and in women partly--be explained by cardiovascular diseases. The 10-yr incidence of DM was 20% if IGT existed at 70, but only 4% when normal glucose tolerance was present at 70.

Short- and long-term variations in non-linear dynamics of heart rate variability.

OBJECTIVES: The purpose of the study was to investigate the short- and long-term variations in the non-linear dynamics of heart rate variability, and to determine the relationships between conventional time and frequency domain methods and the newer non-linear methods of characterizing heart rate variability. METHODS: Twelve healthy subjects were investigated by 3-h ambulatory ECG recordings repeated on 3 separate days. Correlation dimension, non-linear predictability, mean heart rate, and heart rate variability in the time and frequency domains were measured and compared with the results from corresponding surrogate time series. RESULTS: A small significant amount of non-linear dynamics exists in heart rate variability. Correlation dimensions and non-linear predictability are relatively specific parameters for each individual examined. The correlation dimension is inversely correlated to the heart rate and describes mainly linear correlations. Non-linear predictability is correlated with heart rate variability measured as the standard deviation of the R-R intervals and the respiratory activity expressed as power of the high-frequency band. The dynamics of heart rate variability changes suddenly even during resting, supine conditions. The abrupt changes are highly reproducible within the individual subjects. CONCLUSIONS: The study confirms that the correlation dimension of the R-R intervals is mostly due to linear correlations in the R-R intervals. A small but significant part is due to non-linear correlations between the R-R intervals. The different measures of heart rate variability (correlation dimension, average prediction error, and the standard deviation of the R-R intervals) characterize different properties of the signal, and are therefore not redundant measures. Heart rate variability cannot be described as a single chaotic system. Instead heart rate variability consists of intertwined periods with different non-linear dynamics. It is hypothesized that the heart rate is governed by a system with multiple "strange" attractors.

Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductase inhibitors.

Coenzyme Q10 (ubiquinone) the essential mitochondrial redox-component and endogenous antioxidant, packaged into the LDL + VLDL fractions of cholesterol, has been suggested as an important anti-risk factor for the development of atherosclerosis as explained by the oxidative theory. Forty-five hypercholesterolemic patients were randomized in a double-blind trial in order to be treated with increasing dosages of either lovastatin (20-80 mg/day) or pravastatin (10-40 mg/day) over a period of 18 weeks. Serum levels of coenzyme Q10 were measured parallel to the levels of cholesterol at baseline on placebo and diet and during active treatment. A dose-related significant decline of the total serum level of coenzyme Q10 was found in the pravastatin group from 1.27 +/- 0.34 at baseline to 1.02 +/- 0.31 mmol/l at the end of the study period (mean +/- S.D.), P < 0.01. After lovastatin therapy the decrease was significant as well and more pronounced, from 1.18 +/- 0.36 to 0.84 +/- 0.17 mmol/l, P < 0.001. Although HMG-CoA reductase inhibitors are safe and effective within a limited time horizon, continued vigilance of a possible adverse consequence from coenzyme Q10 lowering seems important during long-term therapy.

Structure-activity relationships of novel hematoregulatory peptides.

Hematopoiesis is a lifelong cell renewal process regulated by a family of lineage specific hematopoietic growth factors. Several hematopoietic growth factors such as G-CSF, GM-CSF, and M-CSF have been clinically evaluated for enhancement of host defense in normal and immunocompromised patients and for the treatment of infectious diseases. This paper reports the structure-activity relationships of low molecular weight hematoregulatory peptides based on a nonapeptide (1, SK&F 107647). Like the macromolecular growth factors, these peptides modulate host defense. A molecular target for this class of compounds has not yet been identified. However, the structure-activity relationships established by this study implicate a very specific molecular recognition event that is pivotal for the biological activities of 1 and its analogues.

Haemodynamic effects of single-dose felodipine in normal man.

The haemodynamic effects of an oral solution of 15 mg felodipine were studied in 8 healthy males. Maximal plasma concentrations of felodipine were seen 30 to 40 minutes after administration, when significant decreases in diastolic and mean blood pressures were noted. Heart rate increased maximally by 45% after 30 minutes, accompanied by a 57% increase in cardiac output and 175% increase in forearm blood flow. Total peripheral resistance decreased by 40% and forearm vascular resistance by 66%. Apparent hepatic blood flow was unchanged.

Non-chromogenic peptide substrates for detection of enzymes by means of capacitance changes at metal electrodes.

A new type of substrate for enzyme detection has been developed. The substrate is non-chromogenic and is used in an assay method based on electrode adsorption. The rate of change in the electric capacitance of the electrode is monitored and taken as a measure of the substrate adsorption. Substrate adsorption is in turn proportional to substrate bulk concentration and thus subject to changes by enzymes. The new substrate introduces a new concept in enzyme detection: as it is non-chromogenic it may contain appropriate amino acids on both sides of the bond subject to enzymatic cleavage.

The electrode adsorption method for determination of enzyme activity: a study of substrate requirements.

The electrode adsorption method for the determination of enzyme activity requires substrates that, besides having good kinetics constants for the enzyme, also show good adsorption/desorption kinetics to the electrode surface and adsorb in such a way that they change the double-layer capacitance of the electrode. A series of peptide substrates containing one to three aromatic groups has been synthesized. Our results show that the aromatic groups are of crucial importance for the capacitance change caused by the adsorbing/desorbing substrate. Thus, the tripeptide substrate, Bz-Phe(NO2)-Val-Arg-pNA, with three aromatic groups is superior to the other synthesized substrates containing only one or two aromatic groups. Our desorption experiments show that several factors determine the rate of capacitance increase observed when thrombin is added to a substrate solution in equilibrium with a substrate-covered electrode. The kinetic constants of the substrate determine how the substrate concentration in the solution decreases and, consequently, determine the spontaneous desorption measured as capacitance increase. Thrombin does not seem to split adsorbed substrate molecules but it adsorbs to the substrate-covered surface and in that way causes a capacitance decrease counteracting the change caused by desorption of substrate.

[Sexual activity in ischemic heart disease. Risk and therapeutic possibilities]. / Seksuel aktivitet ved iskaemisk hjertesygdom. Risiko og behandlingsmuligheder.

A major concern of patients with ischaemic heart disease is whether sexual activity is safe. In addition, patients are often reluctant to discuss sexual problems, including erectile dysfunction. Fear of sexual failure or fear of an acute ischaemic cardiac event as a result of sexual activity may create anxiety and lead to avoidance of sexual activity, which can significantly affect quality of life. In patients with a recent acute myocardial infarction the participation in a cardiac rehabilitation program should be strongly encouraged. The results are an improvement in physical capacity and self confidence. The performance of an exercise test at the time of hospital discharge following acute myocardial infarction is mandatory, and can be used in both risk stratification and cardiac rehabilitation. Patients who can manage a work capacity of at least 100 Watt without evidence of myocardial ischaemia or arrhythmias may without concerns take part in an active sexual life. Comprehensive information and appropriate use of pharmacologic agents for erectile dysfunction can add significantly to quality of life.

[Selective screening for hypercholesterolemia. Results from a screening model in general practice]. / Selektiv screening for hyperkolesterolaemi. Resultater fra en screeningsmodel i almen praksis.

At present, it appears to be probable that both dietary changes and medicinal treatment can reduce the risk of development of coronary disease in middle-aged men with moderately to severely raised blood cholesterol values. Internationally, the limits for cholesterol intervention are considerably lower than in Denmark. Extensive cholesterol screening is, however, very expensive and the identified persons with high cholesterol values will frequently be found in sex and age groups where the beneficial effect of intervention is probably limited. A model for selective cholesterol screening in high risk groups in general practice is described here. In 20 general practices, all of the men aged 45-59 years belonging to the practice were invited to examination of cholesterol and blood pressure. Plasma cholesterol was measured by means of a Reflotron (results are available within three minutes) and the blood pressure and tobacco consumption were registered. After this, the patient's own general practitioner calculated with each of the persons the risk for development of myocardial infarction within the next ten years and intervention could be commenced immediately. 41% of those invited came for examination. Out of these, 29% had cholesterol values greater than or equal to 7.0 mmol/l (Danish limiting value), 44% greater than or equal to 6.5 mmol/l (limiting value in the remainder of Western Europe), and 5% greater than or equal to 9.0 mmol/l (severe hypercholesterolaemia) while only 18% had completely normal cholesterol less than 5.2 mmol/l. In every practice, two patients on an average were found with severe hypercholesterolaemia greater than or equal to 9.0 mmol/l. 28% of the participants had at least two of the three risk factors investigated. (ABSTRACT TRUNCATED AT 250 WORDS)

[Formalized dietary advice in hypercholesterolemia. Results in 110 men diagnosed by selective screening in general practice]. / Formaliseret diaetvejledning ved hyperkolesterolaemi. Resultater hos 110 maend diagnosticeret ved selektiv screening i almen praksis.

In connection with a screening investigation for high blood cholesterol in middle-aged men in general practice in the Municipality of Copenhagen, all participants with cholesterol values greater than or equal to 7.5 mmol/l were given brief advice by their own general practitioner and were invited to come for fasting blood lipid tests approximately ten days later. In cases with continued cholesterol greater than or equal to 6.8 mmol/l, the participants together with wives or partners were invited to formalized dietary advice in small groups. Already before the formalized dietary advice, an average decrease in serum cholesterol of 10% was observed. This was attributed to biological variation, absence of fasting, the degree of error between the measuring methods and also a genuine decrease on the basis of the brief dietary advice by the general practitioner. On control after dietary advice, a further decrease in cholesterol of 15% was observed while low density lipoprotein cholesterol fell by 20% and triglycerides by 23%. These decreases must be considered to result mainly from the dietary advice. It is concluded that a single but professional session of dietary advice in small groups and with involvement of the wives or partners is an effective method of treatment in hypercholesterolaemia. If the decrease in cholesterol obtained can be maintained, the literature suggests that the risk of development of ischaemic heart disease during the subsequent 5-7 years is reduced by 20-30%.

[Measurement of blood cholesterol, decentralized, using a Reflotron, or centralized in a laboratory. A comparison]. / Måling af blod-kolesterol decentralt med Reflotron eller centraliseret i laboratorium. En sammenligning.

In connection with an extensive screening programme for blood cholesterol, the cholesterol values in 105 participants were measured on a sample of capillary blood employing a Reflotron and, simultaneously, samples of venous blood were examined by conventional enzymatic analysis in a laboratory. Whereas the day-to-day variation and the scatter involved were quite limited in the laboratory, the variation scatter between the two methods of measurement was 0.65 mmol/l. This figure was, however, no greater than that described between different laboratories in USA. Nevertheless, it is an important problem with the Reflotron method that even slight deviations from the recommended procedure of withdrawing blood involve a systematic risk for erroneously low cholesterol results.

[Dofetilide to patients with heart failure and left ventricular dysfunction]. / Dofetilid til patienter med hjerteinsufficiens og dårligt fungerende venstre ventrikel.

INTRODUCTION: Dofetilide, a new class III antiarrhythmic drug, was tested for its ability to reduce mortality and morbidity in patients with congestive heart failure and left ventricular dysfunction. METHODS: In 34 Danish centers, 1518 patients with NYHA class III or IV heart failure and wall motion index of the left ventricle < or = 1.2 (ejection fraction < or = 35%) were randomized to receive dofetilide or placebo in a double blind study. The dose of dofetilide was adjusted to renal function and the QT interval. Patients were monitored continuously with ekg during the first three days in the study. Minimum follow up was one year. RESULTS: Dofetilide did not affect mortality. Hospitalizations for worsening of heart failure were reduced significantly, hazard ratio 0.75 (0.63-0.89) Dofetilide effectively converted atrial fibrillation to sinus rhythm. After one year, 61% of patients with atrial fibrillation had converted on dofetilide and 33% on placebo (p < 0.001). DISCUSSION: Dofetilide can be used to convert atrial fibrillation to sinus rhythm and to maintain sinus rhythm in patients with congestive heart failure and left ventricular dysfunction. Dofetilide does not affect mortality.

[Screening for cardiovascular risk factors in a large workplace]. / Screening for kardiovaskulaere risikofaktorer på en stor arbejdsplads.

A screening investigation was carried out in a large industry in the Copenhagen region and 1,472 of the employees were offered examination of blood cholesterol and measurement of blood pressure. At this examination the employees completed a one-page questionnaire about other cardiovascular risk factors. 45% of those invited participated in the investigation, the poorest participation was among women and the greatest among the male officials. On account of the limited number of female employees, the majority of results were only calculated for men. Over 1/3 of these had hypercholesteremia (greater than or equal to 7.0 mmol/l) and nearly 1/3 had, simultaneously, at least two cardiovascular risk factors in addition to age and male sex. Extensive occupational investigations under the auspices of WHO have demonstrated that energetic intervention at the place of work aimed at the cardiovascular risk factors can reduce the risk of development of coronary heart disease and death within a six-year follow-up period. It is therefore emphasized that similar interventions are very necessary also in Denmark.