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Biomedical subjects

S Lange

Publications and source records attributed to S Lange.

At least 73 records · Page 4Linked to original sources

Changes of QT dispersion in patients with coronary artery disease dependent on different methods of stress induction.

BACKGROUND: Episodes of stress-induced myocardial ischemia in patients with coronary artery disease (CAD) may cause increases of QT dispersion (QTd). HYPOTHESIS: Aim of this study was to analyze the effect of increasing heart rates on QTd and to compare the effect of different methods of stress induction in patients with varying degrees of CAD when estimating QTd. METHODS: We studied 58 patients, 22 with prior myocardial infarction (MI), 25 without MI or wall motion disturbances at rest, and 11 patients without evidence of CAD. Prior to coronary angiography, standard 12-lead ECGs were obtained at rest as well as during dynamic exercise and pharmacologic stress using arbutamine simultaneously with echocardiography. QTd was determined at each stress level by subtracting minimal from maximal QT interval duration. RESULTS: QTd values at rest were not consistently higher in the patients with CAD. At maximal heart rate, QTd was statistically significantly higher in patients with CAD with a better discrimination between groups for pharmacologic stress (p < 0.005 for exercise, p < 0.0001 for arbutamine). Patients after MI had higher QTd values under all conditions than did the groups without MI. As in patients with CAD, the values of this group changed more radically as a result of pharmacologic stress. CONCLUSION: Patients with CAD can be identified on the basis of QTd under stress. These changes were not as marked in patients with MI as their rest values were already increased. Overall, drug-induced stress produced greater differences than dynamic exercise, suggesting that the ischemic threshold might be lower in the former.

Adrenergic beta-Agonists↗

[Are children properly classified within the scope of expert assessment to determine need for services?].

This project deals with assessment directives issued by the leading statutory care insurance companies to define the need for care of children at certain ages in coping with the activities of daily life specified by the German Social Legislation. The ages in question relate to healthy, normally developed children. They are used as a measure of comparison for the assessment of diseased children. Besides, they have a decisive significance in defining the need for care. Only if a child is not able to perform a certain activity, although it is meant to be able to do so at that age, can we define the need for help and assistance, i.e. care. The project is divided into two sections. 1. Comparison of age mentioned in the assessment directives for each of the daily life activities of healthy and normally developed children aged 1 to 12 years with the age mentioned in technical literature. 2. Comparison of age mentioned in the assessment directives for each ot the daily life activities of healthy and normally developed children at the age of 1 to 12 years with those mentioned in retrospective interviews with the same group of children. In the first part of the project, an analysis of the literature dealing with the subject was done. The literature included the stock of technical literature in the German language. Studying the literature, ages for children could be isolated, that could be classed with the activities of daily life mentioned in the German Social Code. These ages were compared with those in the assessment directives. In a second part of the project, 81 mothers and fathers of healthy, normally developed children aged 1 to 12 years were asked via a questionnaire. They were asked to estimate retrospectively from what age on their child had been able to perform certain activities of daily life without any help. The comparison of ages mentioned in the assessment directives with those of the analysis of literature conformed only regarding daily life activity. Regarding the other activities of daily life the age for children was set higher in the assessment directives than in the literature. Comparing the age of children in the assessment directives with the results of the questionnaires the age was also set higher in the directives than shown by the results of the questionnaires. The results of the literature analysis and the inquiry by questionnaires show that the ages mentioned in the assessment directives for an independent performance of daily life activities do not correspond to the development according to the age of healthy normally developed children aged 1 to 12 years. As a result of this project it seems to be justified to be doubtful about an adequate assessment of children who are in the need of care. Due to this reason it would be desirable to reexamine the data of the assessment directives by means of a new representative prospective study.

Activities of Daily Living↗

Food induced stimulation of the antisecretory factor can improve symptoms in human inflammatory bowel disease: a study of a concept.

BACKGROUND: Antisecretory factor (AF), a 41 kDa cloned and sequenced protein, suppresses intestinal inflammation and hypersecretion in animals. Endogenous AF production can be induced by dietary modifications in several animal species, and this feed has been shown to reduce the incidence of diarrhoeal disease in weaning piglets. The role of AF in intestinal disease in humans is not known. AIMS: To study the effects of hydrothermally processed cereals, optimised for AF induction in animals, added to the diet of patients with longstanding symptoms of inflammatory bowel disease (IBD). PATIENTS: Fifty three patients with IBD (ulcerative colitis and Crohn's disease) were entered into the study, and 50 completed follow up. The experimental group consisted of 16 females (mean age 50 (SEM 5) years) and 10 males (41 (4) years) and the placebo group of 12 women (41 (4) years old) and 12 men (51 (5) years). METHODS: Patients were randomised to receive either hydrothermally processed cereals (active treatment) or the same amount of ordinary cereals (placebo treatment) for four weeks in a double blind study design. Baseline diet and medications remained unchanged. Bowel symptoms, plasma levels of AF, and colonic biopsies were evaluated before and after treatment. RESULTS: The active treatment significantly improved subjective ratings of clinical symptoms and increased plasma AF levels compared with placebo. Plasma lipid levels were unaffected. CONCLUSION: Hydrothermally processed cereals can induce AF production in human IBD. This increase in endogenous AF activity is associated with clinical improvement. Further studies are warranted to clarify the exact role of AF in human intestinal disease.

Adult↗

Energetic requirement of carbachol-induced Ca2+ signaling in single mouse beta-cells.

Insulin secretion is under multifactorial control by glucose and neurohumoral factors like acetylcholine (ACH), which activate the Ca2+/phospholipase C signaling pathway. All insulin secretagogues elevate cytosolic free Ca2+ ([Ca2+]i) that is central to the stimulation of insulin secretion. The actions of ACH on [Ca2+]i are glucose dependent but the metabolic steps involved are only partly understood. Here we have characterized the metabolic steps by which glucose exerts its synergistic effects on ACH-linked Ca2+-signals. [Ca2+]i was measured in single fura-2 loaded beta-cells. The ACH analog carbachol (3 microM) caused rise in [Ca2+]i that was strongly dependent on the extracellular glucose concentration ranging from 0-10 mM. Iodoacetate, which blocks glycolysis, thereby preventing the generation of NADH and ATP from glucose metabolism, and rotenone or antimycin, which inhibit complex 1 and 2 of the mitochondrial respiratory chain, respectively, inhibited in glucose (6 mM) the carbachol-induced Ca2+ signal to a similar extent as glucose deprivation. This demonstrates that glucose metabolism and generation of ATP through oxidative phosphorylation of energy rich substrates like NADH and FADH2 are required for carbachol-induced Ca2+ signals. While sodium arsenate, which prevents net glycolytic production of ATP without inhibiting glycolysis, had no significant effect on the carbachol-induced Ca2+-signal, the mitochondrial pyruvate transport inhibitor alpha-cyano-4-hydroxycinnamate and the Krebs cycle inhibitor monofluoroacetate strongly suppressed the rise in [Ca2+]i elicited by carbachol. While pyruvate was ineffective, methyl pyruvate, a membrane-permeant pyruvate analog, and alpha-ketoisocaproate in combination with glutamine, which are both substrates for mitochondrial ATP production, could restore the carbachol-induced Ca2+ signal in glucose-free medium. These data demonstrate for the first time that Krebs cycle metabolism of glucose and ATP formation through oxidative phosphorylation is critical for the glucose dependency of ACH-linked Ca2+-signals in mouse beta-cells, and they suggest that mitochondrial metabolism plays a key role in the interactive regulation of beta-cells by neurohumoral factors activating the Ca2+/phospholipase C signaling pathway.

Adenosine Triphosphate↗

[Effects of combined dermatological and behavioural medicine therapy in hospitalized patients with psoriasis and atopic dermatitis].

The present study examined the effectiveness of combined dermatological and behavioural medicine therapy on the skin status and disease-specific stress of eighty-six patients with psoriasis and fifty-eight patients with atopic dermatitis who were hospitalized in the PsoriSol Clinic, Hersbruck, Germany. In addition to receiving instruction about their stain disease, the patients were offered, practice in relaxation techniques, social contacts and scratching control as well as individual psychological counselling. The clinical change was assessed by PASI and SCORAD, respectively. The Marburg questionnaire for coping with skin diseases (MHF) and a questionnaire for health-related control attributes (GKU-S) served as psychometric measures. Patients showed significant improvement in skin status and psychosocial parameters in pre-post comparison. Social fears, avoidance and helplessness were reduced by significant improvement of the emotional status in both groups. Patients with psoriasis also showed an increase in internal control attributes. Dermatological treatment combined with behavioural medicine therapy can be considered an effective method in patients with atopic dermatitis and psoriasis.

Adaptation, Psychological↗

[Quality of life in skin diseases: methodological and practical comparison of different quality of life questionnaires in psoriasis and atopic dermatitis].

Aim of the present study was a comparison of four quality of life (QoL) questionnaires in 228 patients with psoriasis (PSO, n = 148) and atopic dermatitis (AD, n = 80) regarding feasibility, discriminant validity and sensitivity to change. Evaluating were performed before and after treatment in clinic. The following questionnaires were compared. 1) Freiburg Quality of Life Assessment for Dermatoses (FLQA-d), 2) Dermatology Life Quality Index (DLQI), 3) Chronic Skin Disease Questionnaire (CSDQ) and 4) questionnaire on everyday life (ALLTAG). All questionnaires were able to discriminate significant reductions of QoL in PSO and AD, as compared to controls. In parallel to the clinical improvement, all questionnaires showed QoL improvements as well, i.e. the questionnaires were sensitive to change. However, not all of the DLQI and ALLTAG scales were sensitive to change. Also, in some cases part of the scales of these questionnaires could not be calculated due to missing data. Otherwise, all questionnaires were valid and easy to handle. Thus, QoL of patients with PSO and AD can reliably be assessed by various questionnaires. Decisive for selection are the aim and the design of the study.

Adult↗

The antisecretory factor: synthesis and intracellular localisation in porcine tissues.

The antisecretory factor, AF, is a 41-kDa protein, cloned and sequenced from a human pituitary library. AF is a potent inhibitor of experimental intestinal hypersecretion in rats and pigs. An antiserum against the C-terminal of the truncated, recombinantly produced AF protein was raised in rabbits. The affinity-purified antiserum was used to study the expression of AF in mucosal membranes and in the pituitary gland of the pig; distinctly stained cells were found in lymphoid cells in the connective tissue of all parts of the gastrointestinal, respiratory and urinary tracts. Cytoplasmic AF was demonstrated in endocrine and epithelial cells in the pituitary gland. In situ hybridisation with a digoxigenin-labelled mRNA probe also demonstrated specific cytoplasmic staining in epithelial and lymphoid cells in all of these tissues. The cells stained by either method were similarly distributed topographically within the tissues. The results suggest that a specific defined cell population in these various tissues possesses the capability of both synthesising and storing the AF protein within the cellular cytoplasmic compartment.

Animals↗

Comparison of the efficacy and safety of aspirin alone with coumadin plus aspirin after provisional coronary stenting: final and follow-up results of a randomized study.

BACKGROUND: The antithrombotic benefit of the conventional treatment with coumadin after coronary stenting is limited by bleeding complications. However, the superiority of an antiplatelet therapy with aspirin alone compared with coumadin plus aspirin has not been proven by randomized studies. The efficacy and safety of treatment with aspirin alone in comparison to coumadin plus aspirin were evaluated in this randomized study. METHODS: Out of 164 patients aged 59.7 +/- 9.2 years, 79 patients were randomly assigned to receive 100 mg aspirin daily (group A) and 85 patients randomly assigned to coumadin plus aspirin (group CA) after provisional coronary stenting with a high-pressure technique. The primary end point was defined as the absence of death, subacute closure of the target vessel, myocardial infarction, urgent coronary bypass surgery, repeated coronary angioplasty, and peripheral vascular complications requiring transfusion or surgery. High-pressure inflation technique was used, but ultrasound guidance was not. RESULTS: During hospitalization (median 8 days), 135 patients (82. 3%) were free of events (A, 84.8%; CA, 80.8%; P =.42). Eleven (6.7%) subacute closures occurred (A, 10.1%; CA, 3.5%; P =.09); 2 of them were lethal in the aspirin group. Emergency bypass surgery was performed in 1 patient in each group. Peripheral vascular complications were observed in 13 patients (7.9%) (A, 1.3%; CA, 14. 1%; P <.01). At 3-month follow-up, 15 (9.1%) elective revascularization procedures (A, 7.6%; CA, 10.6%; P =.51) were performed. CONCLUSION: Aspirin alone at the low dose of 100 mg administered or the combination of coumadin and aspirin after high-pressure coronary stenting does not prevent adverse clinical events when ultrasound guidance is not used.

Angioplasty, Balloon, Coronary↗

Fetal heart rate variability and complexity in the course of pregnancy.

Aim of this study was the examination of fetal heart rate variability and complexity measures during pregnancy using fetal magnetocardiography. We registered 80 fetal magnetocardiograms in 19 healthy fetuses between the 16th and 41st week of gestation. On the basis of beat to beat intervals, mean RR interval (mRR), its standard deviation (SD), root mean square of successive differences (RMSSD), as well as complexity variables such as dimension (ApD1), entropy (ApEn), Lyapunov exponent (ApML) and trajectory divergence rate (p) were calculated for each recording. Dependency of these variables on gestational age was evaluated with correlation analysis. All variables changed consistently over time. RMSSD showed the strongest dependency on gestational age, followed closely by ApEn, SD and p. ApD1 and mRR showed only weak dependency. We conclude that magnetocardiography is well suited to register fetal cardiac activity with sufficient accuracy to permit detailed analysis of various heart rate variables during the second and third trimester of pregnancy. The observed increases in heart rate variability and complexity of fetuses most likely reflect differing but overlapping aspects of fetal development. They may be linked to the maturation of the autonomic nervous system and could aid in the timely identification of pathological conditions.

Adult↗

Biochemical characteristics of Eiseniapore, a pore-forming protein in the coelomic fluid of earthworms.

The cytolytic protein Eiseniapore (38 kDa) from coelomic fluid of the earthworm Eisenia fetida functionally requires sphingomyelin as revealed by using mammalian erythrocytes and phospholipid vesicles. The effects of ions, glycoproteins and phospholipids were investigated for the two-step Eiseniapore action mode, binding and pore formation in different assays. Eiseniapore lysis is activated by thiol groups but inhibited by metal ions. Eiseniapore binding to target membranes is inhibited by Eiseniapore-regulating factor, vitronectin, heparin and lysophosphatidylcholine. Ca2+ and Mg2+ were found to be not necessary for membrane binding or lytic activity. Sphingomyelin was essential for Eiseniapore-induced leakage of liposomes. We describe a cytolytic protein/toxin in Eiseniapore which differs from the established classification; it can be activated by thiol groups and is inhibited by sphingomyelin. Electron microscopy of erythrocyte membranes confirmed ring-shaped structures (pores) with a central channel with outer (10 nm) and inner (3 nm) diameters as shown previously [Lange, S., Nüssler, F., Kauschke, E., Lutsch, G., Cooper, E.L. & Herrmann, A. (1997) J. Biol. Chem. 272, 20 884-20 892] using artificial membranes. Functional evidence of pore formation by Eiseniapore was revealed as protection of lysis by carbohydrates occurred at an effective diameter above 3 nm. From these results, we suggest a plausible explanation for the mechanism by which components of the earthworm's immune system destroy non-self components.

Animals↗

Microwave enhanced ion exchange of cationic and anionic clays.

The ion exchange reactions of both cationic clays (e.g. montmorillonites) and of layered double hydroxides ("anionic clays") are greatly accelerated when carried out under conditions of microwave heating. The observations appear general, and the new methodology should be of considerable importance in many aspects of clay science.

Aluminum Silicates↗

Managing alcohol withdrawal in the acutely ill hospitalized adult.

Managing individuals with acute illness who are at high risk for alcohol withdrawal presents multiple challenges to the treatment teams caring for them. Following realization that management of this group was often characterized by severe withdrawal symptoms (delirium tremens, seizures and the need for leather restraints), a Task Force developed protocols to guide care. Its principal goal was to avoid cardiorespiratory and neurologic morbidities associated with severe withdrawal. The first 441 episodes of care treated after protocol implementation are described in this report. There were no instances of oversedation requiring pharmacological reversal or intubation, few individuals suffered seizures outside of the emergency department and the use of leather restraints declined dramatically. Outstanding issues arising from analysis include the necessity of subjecting the symptom severity instrument to rigorous psychometric study and reconsideration of the appropriateness of a symptom-triggered approach in treating this population. Our experience suggests that use of a nonprescriptive approach by educated and motivated nursing and medical staffs can reduce serious morbidity in this at-risk population.

Acute Disease↗

The 536C-->T transition in the human tissue factor pathway inhibitor (TFPI) gene is statistically associated with a higher risk for venous thrombosis.

Tissue factor pathway inhibitor (TFPI) is an important regulator in the extrinsic blood coagulation pathway. Although the regulatory biochemical role of TFPI is evident, the clinical significance of this proteinase inhibitor remains to be elucidated. The definition of a clinical TFPI deficiency seems to be more complex than that of other coagulation inhibitors because the activity and concentration of circulating TFPI can not be considered a true measure of in vivo levels. Its determination in plasma samples by immunological methods or functional assays has been shown to be inadequate in the detection of a clinical deficiency. Therefore, we screened genomic DNA samples of blood donors and thrombotic patients for alterations in the TFPI gene to assess the influence of a modified TFPI in venous thromboembolic diseases. We detected a single nucleotide substitution in exon 7 (536C-->T) leading to a proline to leucine exchange at amino acid position 151 of the protein ([P151L]TFPI) and found the prevalence of heterozygous carriers in German unrelated blood donors to be 0.2% (n = 5120). Four unrelated persons out of 14 probands carrying the genetic variation could be linked to venous thrombosis. For calculation of a potential risk for venous thrombosis for carriers of the mutation we investigated healthy blood donors about thrombotic events. 7 out of 308 blood donors were found to have a history of venous thrombosis, one of them carried the TFPI mutation. Statistical calculation showed a significant relative risk for venous thrombosis for individuals with the trait (odds ratio, 9.3; confidence interval, 1.8-48.6; p <0.01).

Amino Acid Sequence↗

Spatial distribution of QT dispersion measured by magnetocardiography under stress in coronary artery disease.

This study investigated changes in spatial distribution of QT duration in patients with and without coronary artery disease (CAD) using magnetocardiography. Thirty-six-channel magnetocardiograms (MCGs) were registered at rest and under stress in 15 patients with chest pain, seven of whom had significant coronary stenosis. QT dispersion (QTd) was calculated for MCG and 12-lead electrocardiogram (ECG) under both conditions. For MCG, homogeneity of repolarization was measured using a smoothness index (SI). Also, at each registration site, the intraindividual difference between QT at rest and under stress was determined (deltaQT). QTd values as determined by standard 12-lead configurations were not significantly different between groups. MCG QTd values were significantly higher in the CAD group at rest only when all available channels were taken into consideration (P < .05); SI values differed significantly between groups under both conditions (rest, P < .005; stress, P < .01). Good separation between groups was possible using the range of deltaQT (P < .05) and SI (deltaQT) (P < .005). Consideration of the spatial distribution of QTd increases its sensitivity in the detection of CAD, suggesting that CAD involves complex changes in repolarization, not apparent in limited lead sets such as standard 12-lead configurations.

Adrenergic beta-Agonists↗