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Biomedical subjects

M Schumann

Publications and source records attributed to M Schumann.

At least 19 recordsLinked to original sources

[Self-treatment instruction of patients with type 1 diabetes. Report from hospitals belonging to Working Group for Structured Diabetes Therapy (ASD) in Germany 1998].

AIM: Intensified insulin therapy is the therapy of choice for patients with diabetes Type I. Intensified insulin therapy includes an basis-bolus insulin injection regimen or continuous subcutaneous insulin infusion, several times daily blood glucose self-monitoring, self-adaptation of insulin dosages by the patients themselves and a far-reaching liberalization of nutrition. The patients learn self management of diabetes therapy in a structured treatment and teaching program. The effectivity of this program is evaluated in the routine care. PATIENTS AND METHOD: A peer-review quality circle was formed as an official working group of the German Diabetes Association based on the formation of a working group (Arbeitsgemeinschaft für Strukturierte Diabetestherapie [ASD]) of presently 135 general internal medicine departments from city, country and university hospitals throughout the country. The group attempted to document and to improve the quality of structure and process of Type-I diabetes care in its participating institutions by a system of peer supervision. Systematic follow-up examinations of 50 consecutive Type-I diabetic patients 12 to 15 months after participation in the program confirm the outcome quality. The working group meets every year to discuss the results non anonymously. A PC-system (DIQUAL) was developed for collecting, checking and pooling of the outcome data. RESULTS: From 1992 a representative sample of 6.555 patients with Type-I diabetes was examined. At the first time in 1998 the outcome results of 1.789 patients were analyzed depending on the therapeutic goals. In patients with a high initial HbA1c (> or = 8%) an improvement from 9.8 to 8.0% was reached going together with a reduction of severe hypoglycemia from 0.23 to 0.13/patient/year. In patients with an acceptable initial HbA1c (< 8%) the frequency of severe hypoglycemia could be reduced from 0.65 to 0.24/patient/year without any deterioration in metabolic control. Furthermore the incidence of ketoacidosis with hospitalization and the inpatient days were reduced significantly. CONCLUSION: A substantial improvement of HbA1c and reduction of acute complications, especially of severe hypoglycemia in patients with Type-I diabetes were reached by participation in a structured teaching and treatment programme in clinical routine care.

Blood Glucose Self-Monitoring↗

17beta-estradiol prevents programmed cell death in cardiac myocytes.

The cardioprotective effects of estrogens are clearly established. However, the underlying mechanisms are poorly understood. Because programmed cell death (apoptosis) probably contributes to the loss of cardiac myocytes in heart failure and because estrogens prevent apoptosis in breast cancer cells, we investigated whether the loss of cardiac myocytes by programmed cell death could be prevented by physiological doses of 17beta-estradiol. Apoptosis of cultured cardiac myocytes was induced by staurosporine. 17beta-estradiol (10 nM) had an antiapoptotic effect as determined by morphological analysis, vital staining using the Hoechst dye 33342 and terminal transferase dUTP nick-end labeling (TUNEL). As a potential mechanism for the antiapoptotic effect of 17beta-estradiol we found a reduced activity of the ICE-like protease caspase-3 in hormone-treated myocytes. Furthermore, inhibition of apoptosis by estradiol was associated with a reduced activity of NF-kappaB transcription factors, particularly p65/RelA and p50. To our knowledge, these data provide the first indication that 17beta-estradiol in physiological concentrations inhibits apoptosis in cardiac myocytes. The antiapoptotic effect of estrogens might contribute to the known cardioprotective effect of estrogens and provides a starting point for the development of future treatment options.

Animals↗

Frataxin point mutations in two patients with Friedreich's ataxia and unusual clinical features.

Two patients with a progressive ataxia are presented with clinical features consistent with classic Friedreich's ataxia (FRDA), but also with features unusual for FRDA. Analysis of DNA showed that each patient is heterozygous for the expanded GAA repeat of FRDA, but carries a base change on his other frataxin allele. For one patient a non-conservative arginine to cysteine amino acid change is predicted at amino acid 165 whereas the other mutation is found at the junction of exon one and intron one. Muscle biopsy showed an absence of frataxin immunoreactivity in the patient harbouring the intronic mutation, confirming the pathological nature of the base change. These mutations extend the range of point mutations seen in FRDA, and agree with recent reports suggesting phenotypic variation in patients with FRDA harbouring point mutations in conjunction with an expanded GAA repeat.

Child↗

[Quality management in diabetology by the PC software program DIQUAL].

Today, effective therapies for patients with diabetes mellitus. However, these therapeutic strategies are often not or incorrectly applied. Following these discrepancies for health care providers, it is mandatory to document the efficacy of diabetes treatment. However, it is hard to prove the outcome of diabetes care because of unsuitable documentation, missing parameters and different definitions of quality indicators. The computer programme DIQUAL was developed to improve the diabetes management on the diabetes ward, the diabetes out-patient department and for the documentation of outcome quality. DIQUAL is a patient database and offers structured data collecting and administration, text processing, referring letters, application and list functions, internal and external quality control, as well as cohort or cross-section analysis, data export function for nation wide data collection, system internal plausibility check and extension modules for scientific studies. On the basis of DIQUAL, the first nation wide comparison of outcome quality in the routine treatment of type 1 diabetes was possible. In 1998, we analysed the original data of 1789 patients from 32 district and university hospitals on the basis of the therapeutic goals. HbA1C decreased 1.8% and the incidence of severe hypoglycaemia was lowered to the half. There was a substantial improvement of processes in the health care institutions and the quality of information transmission to the general practitioners. This system of measurement and improvement of quality is also suitable for other areas in health care and medicine.

Ambulatory Care↗

[Nature and frequency of the existence of mold fungi in garbage cans for biological waste and the resultant airborne spore pollution].

In organic waste, numerous mold fungi and other microorganisms develop sometimes within a few hours only which decompose the organic material already in the collecting containers generating heat and odor. With regard to the emission of mold fungus spores out of garbage cans for bio-waste and the potential environmental-hygienic danger connected with it, considerable worries have been expressed recently. A wide spectrum of mold fungi can be found in bio-waste in strongly varying concentrations. No noticeable difference could be ascertained between the settlement structure areas and the cities respectively as to the fungus concentration in the bio-waste substrate. A. fumigatus and A. niger can be recommended as leading spores for the behavior of the total concentration of fungi in the bio-waste due to their frequency of detection and their seasonal dynamism. The intensity of the air spore pollution through emission of mold fungus spores correlates closely with the climatic conditions, such as variations of temperature, relative humidity and solar radiation. The airborne release of mold fungus spores out of garbage cans for bio-waste and the formation of a respective exposure connected with it is judged as harmless for healthy persons. Risk patients and persons having a weakened immune system or assumed to have such a one due to an existent basic illness and/or other reasons should avoid any handling of bio-waste as well as any other waste if possible.

Air Microbiology↗

Modulation of cardiac hypertrophy by estrogens.

Gender-specific differences in heart disease have long been known but it has only been since the advent of molecular biology that it has become possible to investigate the molecular mechanisms. Most biochemical work in the last 50 years has focused on the characterization of the steroid hormones involved in gender specificity. More recently, the cloning of the steroid receptors and characterization of the signaling pathways through these proteins has given new insights into the mechanisms underlying the mode of action of steroid hormones. It has also become clear that the steroid receptors can be classified into families (receptors for thyroid hormone, glucocorticoids, estrogens, androgens, retinoic acid, and so called orphan receptors of mostly unknown function). The structures of these receptors show very close resemblance and all are DNA-binding proteins acting as transcription factors. Some (if not all) act as repressors of transcription of some genes in the native state and are converted to activators (or perhaps repressors of other genes) upon binding of the cognate hormone. Naturally, classical target tissues for estrogens and androgens have been studied first and only in very recent years has it been recognized that estrogens and androgens act on a much wider spectrum of tissues. In the cardiovascular field, the beneficial effect of estrogen replacement therapy in postmenopausal women which reduces the incidence of cardiovascular disease by some 40% and the lower incidence of cardiovascular disease in premenopausal women have mostly been explained by the beneficial action of estrogens on the lipid profile (increase in HDL and decrease in LDL cholesterol). Recently, functional estrogen receptors have also been shown in vascular smooth muscle cells and in the endothelium. Our own group has characterized the presence of estrogen receptors in the myocardium and in cardiac fibroblasts. We have also shown that these receptors are transcriptionally active because they are able to drive a minigene composed of a triple estrogen responsive DNA regulatory element (promoter) coupled to the firefly luciferase gene which serves as a reporter by way of its ability to drive a light-emitting reaction. We are in the process of characterizing the target genes for estrogen in the myocardium. A specific series of immediate-early genes is induced by estradiol (the major premenopausal estrogen) and we have also characterized a number of tissue-specific genes whose expression is driven by estrogens in the myocardium. The ultimate goal of these investigations is to explore the use of estrogens in the treatment of cardiac hypertrophy (and failure) by way of their properties to counteract (at least some of) the pathological switches in gene expression in these disease entities.

Animals↗

Effects of cocaine-induced seizures during pregnancy in the rabbit.

The effects of chronic administration of cocaine to pregnant rabbits on maternal seizures and on pregnancy outcome were studied. Cocaine (2, 3 or 4 mg/kg/injection) or saline was administered, I.V., twice daily, from gestation Day 8 (G8) to G29. There were no significant differences in maternal weight gain or pregnancy outcome between saline control animals and animals given a cocaine dose of 2, 3 or 4 mg/kg/injection. Generalized tonic-clonic seizures (GTCSs) were occasionally elicited by the highest dose (4 mg/kg). There were significant individual differences in vulnerability to cocaine-elicited GTCSs in animals given 4 mg/kg/injection. Of this group, 18% were classified as having high vulnerability to seizures, and they experienced a range from 3 to 27 GTCSs. Postnatal mortality of their offspring was significantly increased. The incidence and temporal patterns of GTCSs elicited by chronic, I.V. cocaine in rabbits, at the doses used, are similar to those reported in human cocaine use. These GTCSs may involve different mechanisms from seizures elicited in other animal studies, in which high doses of cocaine are administered I.P. or S.C. Nevertheless, in our animal model, the GTCSs elicited by prenatal cocaine exposure had no detectable effects on pregnancy outcome (except in the highly vulnerable subgroup).

Animals↗

[Results of revision and new operation in arteriovenous shunt complications].

Over a 10 years period 260 arterio-venous fistulas have been performed and followed up. The Brescia-Ciminoshunt was the most frequent type (n = 174). This type of fistula has been performed in about 85.2% of all cases as primary operation method. In secondary formations the saphena-interposition was used most frequently (49.4% of all cases). A shunt revision should be performed in cases of immediate thrombosis although a shorter life time of revisioned shunts compared with new formations is known. The new formation of a shunt should be considered if terminal thrombotic changes have been detected as well as in cases of shunt infection or shunt insufficiency.

Arteriovenous Shunt, Surgical↗

[Isovolemic hemodilution in central retinal vein occlusion in patients less than 50 years of age].

AIM--Aim of the study was investigation of the effect of isovolemic hemodilution in patients younger than 50 years on the course of central retinal vein occlusion (CRVO) and to compare these results with those of older patients with CRVO. PATIENTS AND METHODS--We performed a prospective study on 35 patients younger than 50 years who were suffering from a central retinal vein occlusion. These patients were all treated by isovolemic hemodilution and compared to a group of older patients with CRVO with the same treatment. RESULTS--About 66% of the younger patients were men compared to only 46% in older patients. At least two cardiovascular risk factors were present in 8.5% of the younger and 54% of the older patients. 16 eyes showed the ischemic, 19 the nonischemic type of CRVO, a similar distribution as in older patients. The course of the disease was more favourable in younger patients, although ocular complications may occur in ischemic CRVO. Isovolemic hemodilution did not change the initial visual acuity of eyes with nonischemic CRVO, but led to an improvement in 56% of the eyes with ischemic CRVO. This means only a minor difference to the course of CRVO in hemodiluted older patients. CONCLUSION--In general, there is no principal difference between the CRVO in younger and older patients, but the course is more favourable in younger patients. On the basis of these findings we recommend isovolemic hemodilution in younger patients with ischemic CRVO.

Combined Modality Therapy↗

Functional and immunological responses of Jurkat lymphocytes transfected with the substance P receptor.

1. We have transfected the rat substance P receptor (SPR) cDNA into the leukemic T-lymphocyte cell line Jurkat (J-wt) in order to study the effects of substance P (SP) on lymphocyte signaling mechanisms and the resultant neuropeptide-induced immunological changes. 2. The SPR cDNA was transfected into J-wt by the method of electroporation. Clones expressing SPRs were selected using a functional assay that measured SP-induced mobilization of intracellular Ca2+ ([Ca2+]i) in a fluorescence activated cell sorter (FACS) and by their expression of specific 125I-SP binding. 3. One clone, J-SPR, was identified and shown by Northern blot and 125I-SP saturation binding techniques to express the 2.2-kb SPR message and approximately 50,000 SPRs/cell with a Kd of 0.3 nM, respectively. Stimulation of J-SPR by SP resulted in the rapid mobilization of [Ca2+]i. This response was dose dependent in the range 10(-11)-10(-6) M SP and was maximal at 10(-7) M SP, with an EC50 of 0.3-0.5 nM SP. We further demonstrated that the SPR is rapidly desensitized following SP stimulation and by activation of the cell's T-cell receptor (TCR). Whole-cell patch-clamp experiments on J-SPR show that SP stimulation induces a Cl- current by a Ca2+ mediated process dependent on Ca2+/calmodulin-dependent protein kinase (CaMK). 4. Stimulation of J-SPR by SP results in changes in the cell surface expression of a number of molecules that play important roles in cell adhesion and activation: the expression of LFA-1 is decreased, and CD2 and IL-2 receptors are increased by 30 min, 6 hr, and 24 hr, respectively, following stimulation, as assessed by antibody staining in a FACS. 5. The expression of functional SPRs in Jurkat lymphocytes will not permit a detailed examination of how the activation of SPRs result in altered immune responses and further elucidate the role this neuropeptide receptor plays in inflammation.

Calcimycin↗

Prostaglandin E1 activates a chloride current in Jurkat T lymphocytes via cAMP-dependent protein kinase.

Patch-clamp studies have identified a cAMP-dependent Cl- conductance in lymphocytes that is defectively regulated in cystic fibrosis. In this study we used 125I efflux and whole-cell patch-clamp studies to investigate whether prostaglandin E1 (PGE1), an agonist that generates intracellular cAMP in Jurkat T lymphocytes, activates a Cl- conductance. Stimulation of T cells by externally applied PGE1 stimulated 125I efflux and activated a slowly developing membrane current. When external and internal Cl- were about equal, the current reversed at about zero mV, but when external Cl- was lowered from 157 to 7 mM the reversal potential shifted 75 mV in the positive direction, demonstrating that the current carrier was Cl-. In addition, the current was blocked by 10 microM 5-nitro-2(3-phenylpropylamino) benzoic acid (NPPB), a potent Cl- channel blocker. A membrane-permeable cAMP analog mimicked the effect of PGE1, whereas intracellular application of a cAMP antagonist Rp-cAMP blocked the effect of PGE1. Addition of purified catalytic subunit of cAMP-dependent protein kinase (PKA) plus ATP to the recording pipette also activated a similar current, whereas internally applied Walsh inhibitor, the synthetic peptide inhibitor of PKA, blocked the PGE1 effect. These results suggest that PGE1, acting through PKA, activates a Cl- current in Jurkat T cells.

Alprostadil↗

[Changes in the spongiosa density in the femoral head of rabbits in atherosclerosis].

Modulations of spongiosa density in the femoral head of rabbits by atherosclerosis. In a long-term study 31 rabbits (+5 control animals) were fed about 20 weeks on a diet rich in cholesterol. An important observation in this study was, that spongiosa density in the femoral head decreases after cholesterol rich diet in contrast to the control group. This effect could be modulated by the Trapidil AR 12463 content (50 mg/die) of the diet, but not by the high density lipoprotein application. Serum cholesterol levels and induced atherosclerosis were determined. Correlations between spongiosa density and atherosclerosis were discussed.

Animals↗

Inotropic effects of the antiarrhythmic compound Bonnecor (AWD 19-166, GS 015).

The inotropic effects of the new antiarrhythmic compound AWD 19-166 have been studied at constantly driven isolated left atria of guinea pig (weight between 250 and 350 g). AWD 19-166 exerted dose-dependently negative inotropic effects. Half maximum effects were measured at 1.7 mg/l (n = 7). At concentrations higher than 5 mg/l the negative inotropic effects were found to be irreversible.

Animals↗

Comparative chemical and immunological characterization of five lipolytic enzymes (carboxylesterases) from rat liver microsomes.

The chemical and immunological properties of five closely related microsomal serine hydrolases (carboxylesterases) from rat liver have been compared to evaluate whether they are variants of a single protein or independent proteins. These enzymes represent medium-chain-length acylcarnitine hydrolase, palmitoyl carnitine hydrolase, medium-chain-length monoglyceride hydrolase, and two long-chain monoglyceride hydrolases. All enzymes have similar subunit Mr's (58,000-61,000) and bear one active site per protein subunit, as could be shown by active sites with radioactive bis(4-nitrophenyl)phosphate, and have subsequently been cleft by proteases or by BrCN. The patterns of radioactive peptides obtained after electrophoresis or thin-layer chromatography indicated that the two long chain monoglyceride hydrolases were closely related, while all other hydrolases differed from these and from each other. The two long-chain monoglyceride hydrolases also had identical N- and C-termini that differed from those of the other hydrolases. All hydrolases contain low amounts of hexoses. It is concluded that the hydrolases investigated represent four independent enzymes with differing amino acid sequences. Three of the four hydrolases were microheterogenous. These results were confirmed with an immunological study using rabbit antisera against three of the hydrolases. Heparin-releasable liver lipase was not cross-reactive with the lipolytic enzymes investigated here.

Amino Acids↗