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Biomedical subjects

S Schmidt

Publications and source records attributed to S Schmidt.

At least 91 records · Page 5Linked to original sources

Inhibitor of complement, Compstatin, prevents polymer-mediated Mac-1 up-regulation of human neutrophils independent of biomaterial type tested.

The inflammatory reaction after cell contact with polymer materials is primarily mediated by activated neutrophils and may, in some cases, lead to exhaustion of neutrophil cell function. A direct consequence of this can be impairment of local or even systemic host defense mechanisms, which in turn can result in foreign body infections. Neutrophil activation, as indicated by the up-regulation of the Mac-1 adhesion receptor, is a reliable parameter for estimating the inflammatory risk due to implanted biomaterials. Because at blood contact, biomaterials immediately acquire a material-specific layer of blood proteins on their surface, including fibrinogen, complement, and immunoglobulin G, it is generally believed that after biomaterial contact, neutrophil activation primarily occurs by interaction with this protein layer. In this study, using our recently established polymer bead in vitro assay, we investigated whether complement inhibition alone can reduce biomaterial-mediated neutrophil activation, independent of the type of polymer and, hence, also its surface chemistry. Complement inhibition was achieved by using Compstatin, a recently developed complement inhibitor that binds to the complement component C3 preventing C3 convertase formation. We revealed significantly reduced (p < or = 0.025) Mac-1 receptor expression levels after 45 min of blood contact with the following polymers (without and with Compstatin): 1. polyurethane, 98.3%, 13.6%; 2. polymethylmetacrylate, 88.5%, 11.0%; and poly-D,L-lactide, 71.8%, 8.4%. Although these three polymer types acquire material-specific protein layers because of their different surface chemistry, complement inhibition by Compstatin alone proved to be sufficient to reduce neutrophil activation after surface contact, thus reducing the risk of biomaterial-mediated inflammatory reaction.

Biocompatible Materials↗

[Assessing the impact of delivery unit size on neonatal survival: estimation of potentially avoidable deaths in Hessen, Germany, 1990-2000].

BACKGROUND AND OBJECTIVE: There are only few analyses from Germany on the impact of delivery unit size on neonatal outcome. The objective of this study was to evaluate the influence of delivery unit size on neonatal survival in Germany. PATIENTS AND METHODS: Data from the perinatal birth register for Hessen for 1990-2000 comprising 640554 births, and the Neonatal Survey for 1989-1997 in Hessen were used. Potentially avoidable deaths were assessed according to delivery unit size and birth weight category. Additionally trend analyses and an extrapolation to potentially avoidable deaths in all of Germany were performed. RESULTS: Compared to large delivery units, smaller ones showed higher risk adjusted mortality rates. Calculation of potentially avoidable deaths gave an estimate of 257 early neonatal deaths in 11 years. Although trend analyses revealed a decline of potentially avoidable deaths, an extrapolation of such deaths for all of Germany still yielded an estimate of more than 300 potentially avoidable deaths per year using data from 1997-2000 only. CONCLUSION: A valid inference as to the magnitude of the observed effect remains even in the face of a very cautious interpretation of our results. During the study period of 11 years, more than 200 neonatal deaths could be attributed to the fact that births in Hessen are dispersed among many small hospitals. If this pattern of births in small units is common throughout Germany, it suggests that several hundred neonatal deaths per year may be attributed to this risk factor when extrapolating these results nationally. Further research is necessary to describe the nation-wide magnitude of this problem and to identify the role of underlying causal risk factors more precisely. Additionally policy discussions regarding structural changes in obstetrical care should be undertaken in the meantime, aimed at reducing the observed mortality rates.

Birth Weight↗

Delta15N values of tropical savanna and monsoon forest species reflect root specialisations and soil nitrogen status.

A large number of herbaceous and woody plants from tropical woodland, savanna, and monsoon forest were analysed to determine the impact of environmental factors (nutrient and water availability, fire) and biological factors (microbial associations, systematics) on plant delta(15)N values. Foliar delta(15)N values of herbaceous and woody species were not related to growth form or phenology, but a strong relationship existed between mycorrhizal status and plant delta(15)N. In woodland and savanna, woody species with ectomycorrhizal (ECM) associations and putative N(2)-fixing species with ECM/arbuscular (AM) associations had lowest foliar delta(15)N values (1.0-0.6 per thousand ), AM species had mostly intermediate delta(15)N values (average +0.6 per thousand ), while non-mycorrhizal Proteaceae had highest delta(15)N values (+2.9 to +4.1 per thousand ). Similar differences in foliar delta(15)N were observed between AM (average 0.1 and 0.2 per thousand ) and non-mycorrhizal (average +0.8 and +0.3 per thousand ) herbaceous species in woodland and savanna. Leguminous savanna species had significantly higher leaf N contents (1.8-2.5% N) than non-fixing species (0.9-1.2% N) indicating substantial N acquisition via N(2) fixation. Monsoon forest species had similar leaf N contents (average 2.4% N) and positive delta(15)N values (+0.9 to +2.4 per thousand ). Soil nitrification and plant NO(3)(-) use was substantially higher in monsoon forest than in woodland or savanna. In the studied communities, higher soil N content and nitrification rates were associated with more positive soil delta(15)N and plant delta(15)N. In support of this notion, Ficus, a high NO(3)(-) using taxa associated with NO(3)(-) rich sites in the savanna, had the highest delta(15)N values of all AM species in the savanna. delta(15)N of xylem sap was examined as a tool for studying plant delta(15)N relations. delta(15)N of xylem sap varied seasonally and between differently aged Acacia and other savanna species. Plants from annually burnt savanna had significantly higher delta(15)N values compared to plants from less frequently burnt savanna, suggesting that foliar (15)N natural abundance could be used as marker for assessing historic fire regimes. Australian woodland and savanna species had low leaf delta(15)N and N content compared to species from equivalent African communities indicating that Australian biota are the more N depauperate. The largest differences in leaf delta(15)N occurred between the dominant ECM Australian and African savanna (miombo) species, which were depleted and enriched in (15)N, respectively. While the depleted delta(15)N of Australian ECM species are similar to those of previous reports on ECM species in natural plant communities, the (15)N-enriched delta(15)N of African ECM species represent an anomaly.

Environmental Monitoring↗

HLA-DR2 dose effect on susceptibility to multiple sclerosis and influence on disease course.

Models of disease susceptibility in multiple sclerosis (MS) often assume a dominant action for the HLA-DRB1*1501 allele and its associated haplotype (DRB1*1501-DQB1*0602 or DR2). A robust and phenotypically well-characterized MS data set was used to explore this model in more detail. A dose effect of HLA-DR2 haplotypes on MS susceptibility was revealed. This observation suggests that, in addition to the role of HLA-DR2 in MS, two copies of a susceptibility haplotype further increase disease risk. Second, we report that DR2 haplotypes modify disease expression. There is a paucity of benign MS and an increase of severe MS in individuals homozygous for DR2. Concepts of the molecular mechanisms that underlie linkage and association of the human leukocyte antigen (HLA) region to MS need to be revised to accommodate these data.

Disease Progression↗

[LDL-Apheresis for the treatment of hyperchylomicronemia-induced pancreatitis].

Severe hyperchylomicronemia due to defects of lipoprotein lipase or apoC-II is a rare cause for acute pancreatitis. Food with a high content of fat, as well as alcoholic or hormonal influences, can lead to excessive hypertriglyceridemia. Especially hyperchylomicronemia due to hormonal influences during pregnancy are troublesome. Here, we are confronted with both the risk to the mother as well as the vital risk to the unborn. Conventional plasma apheresis has been used to successfully eliminate chylomicrons and, thus, the primary cause of chylomicron-induced pancreatitis. Most recently, we reported the use of selective LDL-apheresis in a 24-year-old pregnant woman (thirteenth week of pregnancy), who was admitted with the signs of acute pancreatitis to our hospital. The patient was known to have a history of severe hyperchylomicronemia and she had also been treated several years before for acute pancreatitis by LDL-apheresis. Her triglycerides were severely elevated (11500 mg/dl) and, in order to achieve a rapid decrease of chylomicrons, we decided to treat her by selective LDL-apheresis utilizing HELP-apheresis. The treatment was well tolerated and within half an hour the patient was free of any abdominal pain. However, due to the enormous triglyceride load, we needed to change the precipitate filters several times and at the end of the treatment triglyceride levels were 6600 mg/dl. Under a low-fat diet (<30 gram fat per day), the follow-up was uneventful and the patient delivered a healthy baby at the end of week 39. We conclude that LDL-apheresis is a safe and rapid procedure to eliminate chylomicrons in chylomicron-induced pancreatitis.

Adult↗

Different regulation of the Trio Dbl-Homology domains by their associated PH domains.

Guanine nucleotide exchange factors for Rho-GTPases (Rho-GEFs) invariably share a catalytic Dbl-Homology (DH) domain associated with a Pleckstrin Homology (PH) domain, whose function in Rho-GEF activation is not well understood. Trio is the first member of an emerging family of Dbl proteins containing two Rho-GEF domains (GEFD1 and GEFD2). TrioGEFD1 activates the GTPases RhoG and Rac1, while TrioGEFD2 acts on RhoA. In this study, we have investigated the roles of the two PH domains of Trio in Rho-GEF activity. We show that TrioPH1 is required for GEFD1-mediated induction of actin cytoskeleton remodeling and JNK activation. TrioPH1 is involved both in the catalytic activity and in the subcellular localization of its associated DH domain, by acting as a cytoskeletal targeting signal. Moreover, TrioPH1 in association with DH2 activates the JNK pathway, by an unknown mechanism independent of DH2 catalytic activity. TrioPH2 does not behave as a targeting module in intact cells. TrioPH2 inhibits DH2-dependent stress fiber formation, which correlates with the TrioPH2-mediated inhibition of DH2 GEF activity. In addition, expression in the neuron-like PC12 cell line of the intact Trio protein deleted of each PH domain shows that only TrioPH1 is required for Trio-induced neurite outgrowth. Taken together, these data demonstrate that the two PH domains play a different role in the control of Trio Rho-GEF function.

Animals↗

Local haemodynamics and shear stress in cuffed and straight PTFE-venous anastomoses: an in-vitro comparison using particle image velocimetry.

OBJECTIVES: To use particle image velocimetry (PIV) to study the haemodynamics and shear stress associated with cuffed and straight PTFE-venous anastomoses. METHODS: Silastic models of a straight and cuffed (Venaflo) PTFE-venous anastomoses were attached to a pulsatile flow 'Berlin Heart' circuit filled with glycerine/water and hollow glass tracer spheres. Instantaneous velocity fields were obtained PIV and shear rates and patterns calculated from frame-by-frame analysis. RESULTS: A high velocity jet struck the anastomotic 'floor' and was deflected toward the venous outflow. Shear stresses near the floor were significantly higher, in the straight anastomosis. Sites of high shear stress correlated well with the known sites of intimal hyperplasia. CONCLUSIONS: A cuffed anastomosis type may be favourable in terms of local haemodynamics so enhancing the long-term patency of PTFE-venous grafts.

Anastomosis, Surgical↗

Female alopecia: the mediating effect of attachment patterns on changes in subjective health indicators.

BACKGROUND: The interrelationship between female alopecia and psychological disorders is complex, with a range of psychosocial consequences, but also antecedents. Psychosocial antecedents are to a large extent interpersonal and can be assumed to have a mediating effect on health care utilization and subjective health. OBJECTIVES: To analyse whether changes in health-related quality of life (QoL) are mediated by relational or attachment styles and whether these styles are associated with a particular, dysmorphophobic type of alopecia. METHODS: Seventy-four women with androgenetic and diffuse alopecia underwent psychological assessment at the first consultation at a university clinic and at 2 months' follow-up. Attachment styles were evaluated by an observer rating scale. As a primary endpoint a disease-specific QoL instrument was employed. RESULTS: Findings indicated an association between patients with nonvisible hair loss and the ambivalent attachment style. Global clinical impressions and attachment indicators, e.g. attachment security and coping strategies, showed significant contributions in predicting changes in the QoL scales 'self-esteem' and 'emotions'. CONCLUSIONS: These findings suggest that attachment security may be one of the underlying mechanisms mediating subjective health and that a specific attachment vulnerability can be identified in a subgroup of patients with female alopecia. Future studies will have to focus on the relevance of attachment patterns in the doctor-patient relationship and on psychotherapeutic interventions.

Adaptation, Psychological↗

Coping with chronic disease from the perspective of children and adolescents--a conceptual framework and its implications for participation.

In medical and health psychology, efforts have increasingly been made to assess coping of children and adolescents with chronic conditions. In contrast to the study of coping in adults, approaches to define and assess adaptational processes in children pose a number of problems because coping and development are inherently connected with each other. Issues arising when applying theoretical concepts from developmental psychology to the area of coping in children and adolescents are highlighted. The most prominent approaches to conceptualize and assess coping with chronic disease in childhood and adolescence are illustrated. In future research, there is a need to focus the situational context and content of coping rather than to assess the effort employed and level of a particular coping strategy. Coping is not only a way of regulating emotions, but has an interpersonal meaning, depending on its interactional context. In the medical field, coping has a mediating function for participation and shared medical decision-making in health care processes.

Adaptation, Psychological↗

Advances in EELS spectroscopy by using new detector and new specimen preparation technologies.

First results obtained with a Gatan UHV Enfina system, which was attached to a VG HB 501 UX dedicated STEM, are reported. The Enfina system is based on a CCD detector and offers, compared to the previously used photodiode array, a narrower point-spread function, higher sensitivity, and faster read-out capabilities. These improvements are demonstrated with electron energy-loss measurements on various oxides, such as Al2O3, TiO2 and SrTiO3. It is shown that a better energy resolution is achieved and that acquisition of high-energy absorption edges with a reasonable signal-to-noise ratio becomes possible. Furthermore, we report on the influence of the TEM specimen quality on the energy-loss spectra. Thin amorphous layers at the specimen surfaces, which are induced by ion-milling processes, can modify specific electron energy-loss near-edge structure features. We found that for the investigated ceramics the use of low-energy ion-milling systems is highly recommended, since the loss of energy-loss near-edge structure details by the presence of the amorphous layers is considerably reduced. This is especially true for very thin specimens.

Journal Article↗

[Late results after operative treatment of biliopancreatic cancer].

In this paper the late results after operative therapy of biliopancreatic carcinomas will be presented. Tumors of this region have many things in common. That's why we investigated the 4 tumor entities together. We studied the case histories of 434 patients treated between 1981 and 1997. We analysed the in- and outpatient data of the "Klinikum der Stadt Gera", documents of the tumor board and informations that were obtained from the ambulatory treating physicians. 283 patients suffered from pancreatic carcinoma, 50 from bile duct carcinoma, 60 from gallbladder carcinoma and 41 from carcinoma of the papilla Vateri. The survival rates after curative or palliative operative therapy of the 4 tumor entities were calculated according to Kaplan-Meier. The rate of curative operations and the 5-year-survival-rate after curative resection were 32.8% and 19.0%, resp. in pancreatic carcinoma, 28.0% and 49.0% in bile duct carcinoma, 26.7% and 50.0% in gallbladder carcinoma and 71.0% and 44.0% in carcinoma of the papilla Vateri. Due to the higher resection rate the overall results in patients with carcinoma of the papilla Vateri were much better than the results in the other analysed cancers. Up to now resection is the only way to cure the 4 entities of malignant tumors of the biliopancreatic region.

Age Factors↗

Placement of transjugular intrahepatic portosystemic shunt via the left hepatic vein under sonographic guidance in a patient with right hemihepatectomy.

In a patient with refractory ascites after right hemihepatectomy TIPS was created between the left hepatic vein and the left portal vein via a transjugular approach. The puncture was guided only by sonography from the epigastrium. Portosystemic pressure gradient was reduced from 28 to 7 mm Hg and ascites disappeared. This case shows that TIPS can be created with technical and clinical success after right hemihepatectomy as left hepatic vein to left portal vein shunt under sonographic guidance.

Hepatectomy↗

Increased plasma phenylacetic acid in patients with end-stage renal failure inhibits iNOS expression.

NO prevents atherogenesis and inflammation in vessel walls by inhibition of cell proliferation and cytokine-induced endothelial expression of adhesion molecules and proinflammatory cytokines. Reduced NO production due to inhibition of either eNOS or iNOS may therefore reinforce atherosclerosis. Patients with end-stage renal failure show markedly increased mortality due to atherosclerosis. In the present study we tested the hypothesis that uremic toxins are responsible for reduced iNOS expression. LPS-induced iNOS expression in mononuclear leukocytes was studied using real-time PCR. The iNOS expression was blocked by addition of plasma from patients with end-stage renal failure, whereas plasma from healthy controls had no effect. Hemofiltrate obtained from patients with end-stage renal failure was fractionated by chromatographic methods. The chromatographic procedures revealed a homogenous fraction that inhibits iNOS expression. Using gas chromatography/mass spectrometry, this inhibitor was identified as phenylacetic acid. Authentic phenylacetic acid inhibited iNOS expression in a dose-dependent manner. In healthy control subjects, plasma concentrations were below the detection level, whereas patients with end-stage renal failure had a phenylacetic acid concentration of 3.49 +/- 0.33 mmol/l (n = 41). It is concluded that accumulation of phenylacetic acid in patients with end-stage renal failure inhibits iNOS expression. That mechanism may contribute to increased atherosclerosis and cardiovascular morbidity in patients with end-stage renal failure.

Adult↗

Resistance to glucocorticoid-induced apoptosis in lymphoblastic leukemia.

Glucocorticoid (GC) resistance is a phenomenon of major significance in a number of clinical situations, including the therapy of lymphoid malignancies. Resistance may concern all, or just selected, GC effects, it may be absolute or just reflect a state of reduced sensitivity and, clinically relevant, be reversible or irreversible. Numerous molecular mechanisms can be envisaged acting either 'upstream' in the GC-triggered signaling pathway, i.e. at the level of the GC receptor (GR), or 'downstream' at the level of the GC-regulated genes responsible for individual GC effects. In lymphoid malignancies, GCs have anti-leukemic effects through the induction of apoptosis and/or cell cycle arrest. In this condition evidence for only a small number of mechanisms for GC resistance has been provided, mostly at the level of the GR. Herein, we review reports and hypotheses regarding 'upstream' and 'downstream' mechanisms for GC resistance in lymphoblastic leukemia and present an in vitro GC resistance model that might allow identification of resistance mechanisms.

Apoptosis↗

In vivo test systems for the quantitative and qualitative analysis of the biological activity of phytoestrogens.

Many compounds of plant origin with the ability to bind to the estrogen receptor have been identified in the last decades. One of the most extensively used in vivo assays to characterise the estrogenic potency of these phytoestrogens and mechanisms of their action is the rodent uterotrophic assay. Various protocols exist for this test system, using immature, hypophysectomized, or ovariectomized rats and mice and oral or subcutaneous administration of the test compound. However, just monitoring the ability of a compound to stimulate uterine growth is not sufficient to characterize its estrogenicity. Over the last decades, an increasing number of estrogen sensitive tissues has been identified. Moreover, a variety of different molecular mechanisms have been discovered for the action of estrogens, including non-genomic actions. Therefore, an in vivo test design for estrogenicity should include an analysis of several estrogen sensitive parameters in different estrogen sensitive tissues. To distinguish between agonistic and antagonistic properties of a substance, combinations of the test compound with estrogens and antiestrogens should be analyzed. A reasonable supplement to this enhanced uterotrophic assay are selected estrogen sensitive tumor models, which can be used to test for potential chemopreventive properties of phytoestrogens.

Animals↗

[Laparoscopic transhiatal approach to epiphrenic esophageal diverticula].

INTRODUCTION: The operative treatment for epiphrenic diverticula is usually performed via thoracotomy or laparotomy. PATIENTS AND METHODS: Alternatively we describe the feasibility of a laparoscopic transhiatal approach in three consecutive symptomatic patients with four epiphrenic diverticula. In all cases, the diverticula were completely resected laparoscopically in combination with an esophagomyotomy and a posterior partial fundoplication. RESULTS: The three patients showed uneventful postoperative courses with a speedy recovery and are symptom-free after a follow-up of 22-41 months. CONCLUSION: Our results demonstrate that laparoscopic transhiatal procedure in patients with symptomatic epiphrenic diverticula can be performed safely, effectively, and gently.

Aged↗

Kinetics, energetics, and electronic coupling of the primary electron transfer reactions in mutated reaction centers of Blastochloris viridis.

Femtosecond spectroscopy in combination with site-directed mutagenesis has been used to study the dynamics of primary electron transfer in native and 12 mutated reaction centers of Blastochloris (B) (formerly called Rhodopseudomonas) viridis. The decay times of the first excited state P* vary at room temperature between of 0.6 and 50 ps, and at low temperatures between 0.25 and 90 ps. These changes in time constants are discussed within the scope of nonadiabatic electron transfer theory using different models: 1) If the mutation is assumed to predominantly influence the energetics of the primary electron transfer intermediates, the analysis of the room temperature data for the first electron transfer step to the intermediate P(+)B(A)(-) yields a reorganization energy lambda = 600 +/- 200 cm(-1) and a free energy gap Delta G ranging from -600 cm(-1) to 800 cm(-1). However, this analysis fails to describe the temperature dependence of the reaction rates. 2) A more realistic description of the temperature dependence of the primary electron transfer requires different values for the energetics and specific variations of the electronic coupling upon mutation. Apparently the mutations also lead to pronounced changes in the electronic coupling, which may even dominate the change in the reaction rate. One main message of the paper is that a simple relationship between mutation and a change in one reaction parameter cannot be given and that at the very least the electronic coupling is changed upon mutation.

Alphaproteobacteria↗