Search PubMed⌕ Search

Biomedical subjects

L Heinemann

Publications and source records attributed to L Heinemann.

At least 73 records · Page 4Linked to original sources
PubMed1996

Interim review of the Transnational Case-control Study of Oral Contraceptives and Health: approved protocol revisions through September 1995.

UNLABELLED: The protocol of the Transnational Study on Oral Contraceptives has been published at the outset of the study in order to ensure the correct performance of the study and to ensure the study's scientific integrity. Potential revisions and additions to this protocol had been announced in the prior publication. This article focuses on those points of protocol which have been resolved as practical experience was gathered as well as additional modifications required by practical and scientific considerations. The major alterations are based on exposure prevalences in controls and on power calculations. The low (1.8%) exposure to gestodene among German controls led to the discontinuation of the German component and to the accelerated accession in additional countries. THE CASE: control ratio was altered to 3:1 for purposes of economy based on power calculations. Numerous minor points, most addressed in the prior protocol, have been resolved. It is found that these modifications of the study protocol do not impair the study's conduct, its scientific integrity, nor its capability of providing answers to the study question.

Journal Article↗
PubMed1996

[Quantitative assessment of amounts consumed using the combined methods of a food frequency questionnaire and a 3-day dietary protocol].

With this paper we attempt to present a possible way of making quantitative estimates of the quantities of selected, preventively important food stuff groups consumed using a food frequency questionnaire together with a 3-day dietary protocol. The 3-day dietary protocol used in the 1984/85 MONICA survey of the former GDR is used as the standard. For large nutritional/epidemiological studies (e.g., cancer or cardiovascular cohort studies) this combination of methods is suggested as a means of arriving at quantitative estimates for nutritional habits in relation to the product groups presented here. Further investigations regarding correction factors are necessary where the food frequency is either very low or very high to detect potential inaccuracy.

Adult↗
PubMed1996

Coronary heart disease mortality, morbidity, and case fatality in five east and west German cities 1985-1989. Acute Myocardial Infarction Register Teams of Augsburg, Bremen, Chemnitz, Erfurt, and Zwickau.

Cardiovascular mortality (CVD; International Classification of Diseases [ICD] 390-458) is higher in East than in West Germany, but the differences in official coronary heart disease mortality (CHD; ICD 410-414) are not so pronounced. The aim of this study was to validate the official mortality statistics based on the five German AMI registers and to analyze whether these mortality differences are due to differences in the attack rates of acute myocardial infarction (AMI) or to differences in the 28-day case fatality rates. This comparison includes the MONICA study cities of Augsburg and Bremen, both in West Germany, as well as the cities of Chemnitz, Erfurt, and Zwickau in East Germany (former the German Democratic Republic). The rates were calculated on the basis of all MONICA cases of definite AMI or coronary death aged 35 to 64 years occurring in the respective study populations between 1985 and 1989. All study populations except women in Augsburg showed higher coronary death rates compared to the rates based on the official cause of death statistics (ICD 410-414), but this difference was significant only for men in Chemnitz. In men there were no significant differences in the register-based coronary death rates between these urban areas (160/100,000 in Zwickau to 170/100,000 in Chemnitz) nor in the AMI attack rates (327/100,000 in Augsburg to 363/100,000 in Chemnitz), and consequently no significant center differences in the overall 28-day case fatality. However, the prehospital case fatality was significantly higher in Erfurt (34%) than in Bremen (27%). There were no significant differences in the AMI attack rates in women as well (60/100,000 in Chemnitz to 70/100,000 in Bremen and Erfurt), but the overall 28-day case fatality showed a clear gradient from the East (61-71%) to the West German cities (48-56%) and therefore also the register-based coronary death rates (38-50/100,000 and 34-38/100,000, respectively). However, the higher 28-day case fatality in women found in the MONICA registers in East compared to West Germany is not reflected in the CHD mortality statistics because of a stronger underestimation of the official mortality rates and in East than in West Germany, in particular in women. Nevertheless, the total mortality rates and in most cases also the CVD mortality rates were in women significantly higher in the East German compared to the West German cities. The East German official preunification CHD mortality data cannot be used for national and international comparisons. The results of the MONICA AMI registers in East and West Germany indicate, furthermore, the need to improve coronary care in women in the eastern part of the country. Nevertheless, because of the relatively high AMI attack rate in both parts of Germany primary prevention must generally be intensified.

Adult↗
PubMed1996

Effects of smoking on blood pressure and proteinuria in patients with diabetic nephropathy.

OBJECTIVES: To investigate the effects of smoking on blood pressure and proteinuria in hypertensive diabetic patients with nephropathy. DESIGN: Controlled, randomized, cross-over study. SETTING: Tertiary care centre, University Hospital of Düsseldorf, Germany. SUBJECTS: A total of 25 subjects were recruited, each of whom smoked at least 20 cigarettes a day: 10 normotensive healthy volunteers and 15 hypertensive type 1 (insulin-dependent) diabetic outpatients with diabetic retinopathy and persistent micro- or macroalbuminuria; 10 diabetic patients had normal autonomic function test, whilst five patients showed signs of autonomic neuropathy. INTERVENTIONS: Controlled smoking or nonsmoking over a period of 8 h on separate days. MAIN OUTCOME MEASURES: Blood pressure was measured every 10 min with an automatic device and urine samples were collected every 3 h. RESULTS: Systolic blood pressure increased during smoking in controls (mean) (11.5 mmHg, P = 0.0001) and in diabetic patients without autonomic neuropathy (7.9 mmHg; P = 0.018), but not in patients with autonomic neuropathy (-2.4 mmHg; P = 0.792). Diastolic blood pressure increased during smoking in controls (6.2 mmHg; P = 0.019) but not in diabetic patients (2.5 mmHg; P = 0.204. 0.2 mmHg; P = 0.956). During smoking, median proteinuria and albuminuria increased in diabetic patients without autonomic neuropathy (8.1 mg mmol-1 creatinine, P = 0.002; and 2.6 mg mmol creatinine, P = 0.084). No significant changes in albuminuria or proteinuria occurred in the other two groups. CONCLUSIONS: Smoking increases blood pressure values in healthy subjects and in hypertensive patients with diabetic nephropathy and without autonomic neuropathy. This effect of smoking may be partly responsible for the faster progression of diabetic nephropathy in smoking diabetic patients.

Adult↗
PubMed1996

Effects of enalapril and nitrendipine on exercise albuminuria in normotensive type I diabetic patients with incipient nephropathy.

Based on animal experiments it has been proposed that antihypertensive agents may differentially influence albuminuria through their divergent effects on glomerular haemodynamics or glomerular sieving properties and may beneficially influence the progression of diabetic nephropathy even without an effect on blood pressure. However, to date this hypothesis has not been tested in normotensive patients with diabetic nephropathy. The main aim of this study was therefore to investigate the effects of the administration of two antihypertensive agents on albuminuria during rest and exercise. The study consisted of 3 x 3 randomised, cross-over periods with five days double blind administration of enalapril (E: 2.5 mg bid), nitrendipine (N: 5 mg bid) and placebo (P) on 18 Type 1 normotensive (blood pressure < 140/90 mmHg) diabetic patients with incipient diabetic nephropathy (albuminuria 30-300 mg/24 h, normal glomerular filtration rate, diabetes duration > 6 years and presence of diabetic reinopathy. The aim of this study was to investigate the effect of enalapril and nitrendipine on blood pressure values and albuminuria during exercise challenge (bicycle ergometry: 20 min at 75 W and 20 min at 100 W) in comparison to the placebo. Albumin excretion rates during pre-exercise rest (mean +/- SD; E: 6.2 +/- 6.0; N: 7.1 +/- 8.0; P: 7.7 +/- 7.0 mg/mmol creatinine) and during exercise (E: 8.7 +/- 9.4; N: 8.2 +/- 8.2; P: 11.1 +/- 11.4 mg/mmol creatinine) were comparable between the drugs and not significantly different after administration of placebo. Blood pressure values were significantly different between the medications (systolic blood pressure: p = 0.0269; diastolic blood pressure: p = 0.0021, ANOVA for repeated measurements). There were no significant correlations between blood pressure values and albuminuria at any time. In normotensive patients with incipient diabetic nephropathy low-dose administration of enalapril, nitrendipine and placebo does not result in clear cut differences in albuminuria.

Adolescent↗
PubMed1996

Cyproterone acetate: is it hepato- or genotoxic?

The preclinical safety assessment of cyproterone acetate (CPA) with regard to liver tumorigenesis was based on tumorigenicity studies, which revealed no mutagenic potential. Recently, in vitro studies on the formation of adducts and the enhancement of DNA repair synthesis with CPA have been published. These results are not unique to CPA, and the role of adducts and increased DNA synthesis in mutagenesis is still not clear. Dose-related hepatic toxicity has been reported with the prolonged use of CPA. An active surveillance study of patients taking long term CPA treatment has shown no correlation between the duration of CPA treatment and the prevalence of liver enzyme elevations. In a multicentre surveillance study of long term CPA use in 2506 patients included so far, not a single case of hepatocellular carcinoma has been observed. These findings do not support the theory of an elevated risk of hepatocellular carcinoma as a result of CPA treatment. In conclusion, there have been no observations which could point to an increased risk of proliferative liver change as a result of CPA treatment.

Androgen Antagonists↗
PubMed1996

Ø[The effect of physical exercise on glycemia on healthy subjects following administration of glimepiride].

Sulfonylureas predispose to hypoglycaemia during and after exercise. The hypoglycaemic effect of the novel sulfonylurea glimepiride (G; CAS 93479-97-1) in male healthy volunteers under these conditions. Each subject was exposed to three experimental situations, administration of 3 mg G and rest, administration of 3 mg G and 60 min of bicycle ergometry (E) (work load adjusted to a heart rate of 120 bpm), or placebo (P) and bicycle ergometry as mentioned. Each of these was preceded and followed by 60 min of physical rest. Base line glycaemia was comparable (PE 83 +/- 8 mg/dl, GR 84 +/- 5 mg/dl, GE 86 +/- 7 mg/dl) and fell during GR to 63 +/- 6 mg/dl after 150 min. During GE glycaemia ceased to decline after 30 min exercise, and rose thereafter reaching values comparable to PE after 150 min (80 +/- 8 vs. 82 +/- 7 mg/dl). Serum insulin concentrations rose during exercise following administration of G to 6-7 microU/ml (AUC during the period 60-120 min after administration: GE 371 +/- 81 microU/ml.60 min, GR 414 +/- 77 microU/ml.60 min), and fell during PE to 4 microU/ml (265 +/- 49 microU/ml.60; p < 0.001 vs. GE and GR). During GE serum insulin concentrations fell to 6 microU/ml at the end of exercise and thereafter (AUC during the period 120-180 min after administration: 340 +/- 82 microU/ml.60 min), whereas they remained at 7 microU/ml during GR (399 +/- 109 microU/ml.60 min; p = 0.087 vs. GE). In conclusion, exercise blunts the hypoglycaemic effect of glimepiride in healthy individuals.

Adult↗
PubMed1995

Fitting nonlinear regression models with correlated errors to individual pharmacodynamic data using SAS software.

Nonlinear regression is widely used in pharmacokinetic and pharmacodynamic modeling by applying nonlinear ordinary least squares. Although the assumption of independent errors is frequently not fulfilled, this has received scant attention in the pharmacokinetic literature. As in linear regression, leaving correlation of errors out of account leads to an underestimation of the standard deviations of parameter estimates. On the other hand, the use of models that accommodate correlated errors requires more care and more computation. This paper describes a method to fit log-normal functions to individual response curves containing correlated errors by means of statistical software for time series. A sample computer program is given in which the SAS/ETS procedure MODEL is used. In particular, the problem of finding appropriate starting values for nonlinear iterative algorithms is considered. A linear weighted least squares approach for initial parameter estimation is developed. The adequacy of the method is investigated by means of Monte Carlo simulations. Furthermore, the statistical properties of nonlinear least squares with and without accommodating correlated errors are compared. Time action profiles of a long-acting insulin preparation injected subcutaneously in humans are analyzed to illustrate the usefulness of the method proposed.

Dose-Response Relationship, Drug↗
PubMed1995

Trend of cardiovascular risk factors in the East German population 1968-1992.

The deteriorating trend of life expectance since the mid 1970s, mainly due to higher cardiovascular mortality in the East compared to West Germany, requires explanations about what happened to the cardiovascular risk factor profile in the East. Epidemiologic studies in the East German population have been performed for about 25 years and can justify a first answer to the question, whether the opening gap in life expectancy could be attributable to a deteriorating cardiovascular risk factor profile of the 25-64 year old population. During a review process reliable epidemiological studies in the East German population have been identified to describe sequential changes from 1968 to 1992 in systolic and diastolic blood pressure (SBP, DBP) total cholesterol (CHOL), body mass index (BMI) and cigarette smoking in five periods of time. The mean SBP increased in males of higher age groups, whereas it dropped in females in all age groups in this period of time. The mean CHOL showed a striking increase in both sexes and levelled off in the mid 1980s only. The mean BMI increased slightly in men of the middle age groups and remained almost unchanged in women. The prevalence of cigarette smoking increased in both sexes until the 1970s, and declined thereafter in the age groups over 40, however, there is an increasing tendency in young age groups and females after the wall came down. These trends are congruent with the hypothesis, that the increasingly unfavourable trend of life expectancy in East Germany (compared to the continuously improving trend in West Germany) is at least partly attributable to the trend of the cardiovascular risk factor profile.

Adult↗
PubMed1995

Effect of 4-hour hyperglycaemia and hyperinsulinaemia on plasma atrial natriuretic factor concentrations.

To elucidate the mechanism behind the increased plasma atrial natriuretic factor (ANF) reported in Type 1 diabetic patients with glomerular hyperfiltration and incipient nephropathy, we studied the effects of a short-term moderate hyperglycemia with concomitant hyperinsulinaemia on plasma ANF concentrations and glomerular filtration rate (GFR) in healthy male volunteers. Following a 2-hour basal run-in period, blood glucose level was clamped at 12.2 mmol/l for 4 hours by infusing 20% glucose solution (hyperglycaemia study) or the level was kept normal by infusing isotonic saline over the 4 hours (saline control study). Plasma ANF increased slightly both in the hyperglycaemia phase (from 25.7 +/- 6.3 to 32.1 +/- 7.5 ng/l at 3 hours [p < 0.02] and 31.0 +/- 6.6 ng/l at 4 hours [p = 0.058, mean +/- SD]) and in the control phase (from 17.7 +/- 6.1 to 26.1 +/- 13.5 ng/l at 3 hours [p < 0.05] and 25.4 +/- 11.7 ng/l at 4 hours [p < 0.05]) as compared with the respective baseline values. GFR remained unchanged both in the hyperglycaemia (from 108 +/- 8 to 104 +/- 13 ml/min/1.73 m2) and the saline control phases (from 106 +/- 7 to 101 +/- 7 ml/min/1.73 m2), respectively. The results of this short-term study showed no association between the moderate hyperglycaemia with a concomitant hyperinsulinaemia and plasma ANF concentration in non-diabetic normotensive subjects.

Adult↗
PubMed1995

Four week administration of an ACE inhibitor and a cardioselective beta-blocker in healthy volunteers: no influence on insulin sensitivity.

In most, but not all, studies antihypertensive treatment with angiotensin converting enzyme inhibitors (ACE inhibitors) improves insulin sensitivity, whereas beta-blockers decrease insulin sensitivity. However, there was a significant increase in body weight with beta-blockers and changes in the body potassium homeostasis with ACE inhibitors. In order to compare the drug specific metabolic effects of an ACE inhibitor and a cardioselective beta-blocker controlling these factors, we measured insulin sensitivity in a randomized, double-blind cross-over study in 22 healthy volunteers (age 27 +/- 3 years; BMI 22.0 +/- 1.5 kg m-2 (mean +/- SD)) during euglycaemic glucose clamps before and after 4 weeks' administration of 5 mg Lisinopril or 5 mg Bisoprolol. Both drug phases were separated by 4 weeks of no drug administration. During the insulin sensitivity measurements potassium concentrations were clamped at basal levels by means of a variable i.v. potassium infusion. Body weight was monitored at weekly intervals and kept constant within +/- 1 kg of the subjects' baseline weight throughout the entire study period. Insulin sensitivity did not change significantly during either drug administration period. The insulin sensitivity index of the 22 volunteers after administration of the ACE inhibitor was 7.9 +/- 2.4 mL min-1 m2 microU-1 mL-1 (basal index 8.3 +/- 1.9 mL min-1 m2 microU-1 mL-1, and 7.5 +/- 2.1 mL min-1 m2 microU-1 mL-1 after administration of the beta-blocker (basal index 8.2 +/- 1.9 mL min-1 m2 microU-1 mL-1; NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1995

Community-based stroke incidence trends from the 1970s through the 1980s in East Germany.

BACKGROUND AND PURPOSE: Stroke mortality has declined in most industrialized countries, but incidence rates have increased in some populations while they remained stable or even decreased in others. This study reports stroke incidence trends in East Germany over the past decades. METHODS: Prospective community-based stroke registers were run in East Germany over two different time periods: 1972 through 1973 in the Berlin-Lichtenberg district and 1985 through 1988 in 14 districts in the central and southern part of the country. Stroke cases were collected and validated in a uniform way using both the World Health Organization (WHO) recommendations for community stroke registers and the guidelines of the WHO MONICA protocol. RESULTS: Annual age-adjusted incidence rates of first-ever strokes rose among men aged 25 to 64 years from 48.4 per 100,000 in 1972 through 1973 to 88.0 per 100,000 in 1985 through 1988 (P < .05); incidence rates remained unchanged among women in this age range (52.6 and 52.5 per 100,000, respectively). Age-specific incidence rates increased among men in all age groups up to 74 years. Rising stroke rates were also observed in women under 55 years and between the ages of 65 and 74 years, whereas in women aged 55 to 65 years incidence rates declined by more than a third (P < .05). During the period from 1985 through 1988, stroke rates did not change. CONCLUSIONS: An increase in stroke incidence was detected that can be associated with a deteriorating risk factor profile in the East German population and, in particular, with hypertension in men.

Adult↗
PubMed1995

Time-action profiles of the intermediate-acting insulin analogue des(64,65)-human proinsulin.

Des(64,65)-proinsulin (DPRO) is one of several endogenous intermediates arising during the conversion of proinsulin to insulin. In pharmaceutic preparations it is a clear solution containing no other proteins. Animal experiments and preliminary human studies indicated that DPRO should have a protracted time-action profile similar to that of NPH-insulin. Accordingly, we compared the time-action profiles of these two preparations, using the euglycaemic glucose clamp-technique in 9 healthy male volunteers. Different doses of DPRO (0.1, 0.15, 0.2 U/kg) or equipotent doses of NPH ( 0.2, 0.3, 0.4 U/kg) were injected subcutaneously into the abdominal wall. The maximal metabolic effect (GIRmax) of DPRO was greater than that of NPH-insulin (p < 0.05). With increasing doses, GIRmax differed significantly for DPRO but not for NPH-insulin. The time to maximal metabolic effect (tmax) was similar for the three doses of either preparation. However, tmax was reached 30 min earlier with DPRO than with NPH-insulin (p < 0.01). the decline to half-maximal after maximal activity was significantly faster with DPRO than with NPH-insulin (p < 0.0001). Subcutaneous injection of DPRO thus produced a time-action profile between that of regular insulin and NPH-insulin.

Adult↗
PubMed1994

Effect of insulin concentration, subcutaneous fat thickness and skin temperature on subcutaneous insulin absorption in healthy subjects.

Subcutaneous insulin absorption kinetics were assessed in 50 healthy study subjects (21 female, 29 male; age 26 +/- 3 years, BMI 22.5 +/- 1.8 kg/m2; mean +/- SD) during 45 min after periumbilical injection of soluble human U40- or U100-insulin (0.15 IU/kg). Subcutaneous fat thickness was measured by ultrasound, and skin temperature at the injection site was registered. Serum insulin concentrations increased within 30 min from basal values of 37 +/- 15 to 140 +/- 46 pmol/l after U40-insulin and from 36 +/- 10 to 116 +/- 37 pmol/l after U100-insulin (p < 0.001). After 45 min serum insulin concentrations were 164 +/- 43 pmol/l with U40-insulin and 128 +/- 35 pmol/l with U100-insulin (p < 0.001). Decline in blood glucose levels and suppression of C-peptide were comparable. The serum insulin levels reached 30 and 45 min after U40- and U100-insulin injection were positively correlated with skin temperature (p < 0.0008), and negatively correlated with subcutaneous fat thickness (p < 0.009). In conclusion, the lower insulin concentration of U40-insulin, higher skin temperature, and a thinner subcutaneous fat tissue at the injection site are associated with accelerated and enhanced subcutaneous insulin absorption.

Absorption↗
PubMed1994

Comparative dose-related time-action profiles of glibenclamide and a new non-sulphonylurea drug, AG-EE 623 ZW, during euglycaemic clamp in healthy subjects.

Insulin and glucose responses to glibenclamide were studied in comparison to a novel non-sulphonylurea drug (AG) by means of the euglycaemic clamp technique. Nine fasting male subjects were connected to a Biostator and 1.75, 3.5 or 7.0 mg glibenclamide or 1.0, 2.0 or 4.0 mg AG were given and blood glucose concentrations were clamped at 10% below basal values. Glucose infusion rates were registered over 10 h after administration of the tablet. Maximal glucose infusion rates after glibenclamide were 40% higher compared to AG (1.75 vs 1.0 mg, 3.5 vs 2.0 mg, 7.0 vs 4.0 mg, respectively) and were reached after 3-3.5 h for all doses. After glibenclamide, area under the glucose infusion curves and maximal incremental serum insulin responses were higher by 25-40% and by 30% compared to AG when low, medium and high doses of each drug were tested. However, a linear dose relationship was obtained for both drugs when the glucose infusion rate was plotted against the area under the insulin curve. In fact, both drugs were equipotent on a molecular weight basis. The hypoglycaemic index of both drugs (integrated glucose infusion rate divided by integrated insulin release) expressed per mumol of drug revealed a dose-dependent and parallel inverse curvilinear relation to increasing doses. This methodological approach allowed us to quantify and compare the metabolic effects of oral hypoglycaemic agents under standardised experimental conditions.

Administration, Oral↗