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Biomedical subjects

H Schubert

Publications and source records attributed to H Schubert.

At least 19 recordsLinked to original sources

Fetal body weight and the development of the control of the cardiovascular system in fetal sheep.

Reduced birth weight predisposes to cardiovascular diseases in later life. We examined in fetal sheep at 0.76 (n = 18) and 0.87 (n = 17) gestation whether spontaneously occurring variations in fetal weight affect maturation of autonomic control of cardiovascular function. Fetal weights at both gestational ages were grouped statistically in low (LW) and normal weights (NW) (P < 0.01). LW fetuses were within the normal weight span showing minor growth dysproportionality at 0.76 gestation favouring heart and brain, with a primary growth of carcass between 0.76 and 0.87 gestation (P < 0.05). While twins largely contributed to LW fetuses, weight differences between singletons and twins were absent at 0.76 and modest at 0.87 gestation, underscoring the fact that twins belong to normality in fetal sheep not constituting a major malnutritive condition. Mean fetal blood pressure (FBP) of all fetuses was negatively correlated to fetal weight at 0.76 but not 0.87 gestation (P < 0.05). At this age, FBP and baroreceptor reflex sensitivity were increased in LW fetuses (P < 0.05), suggesting increased sympathetic activity and immaturity of circulatory control. Development of vagal modulation of fetal heart rate depended on fetal weight (P < 0.01). These functional associations were largely independent of twin pregnancies. We conclude, low fetal weight within the normal weight span is accompanied by a different trajectory of development of sympathetic blood pressure and vagal heart rate control. This may contribute to the development of elevated blood pressure in later life. Examination of the underlying mechanisms and consequences may contribute to the understanding of programming of cardiovascular diseases.

Animals↗

Anodic cell-protein deposition on inverse inkjet printed micro structured gold surfaces.

The transformation of fibrinogen into fibrin is biologically activated in a complex multi-step process known as the coagulation cascade. This transformation can also be triggered by anodic surfaces. It has been suggested that this mechanism is a result of an electron transfer from the anode to the fibrinogen molecule resulting in the formation of fibrin. In this study we used this pathway to simultaneously deposit vital cells (fibroblasts and keratinocytes) and fibrin on micro structured gold electrodes. The electrodes were produced using a novel inverse inkjet-printing technology in combination with subsequent gold-sputtering, resulting in minimal structure-sizes of 35 microm (+/-6 microm). Cell deposition and fibrin-coagulation were found to occur on the anode only, following exactly the micro structured electrode surface. Successful deposition was limited by the minimal voltage (0.8 V) needed for the formation of fibrin and the maximum voltage (1.85 V) resulting in the deterioration of the Au-electrodes due to electrolysis and possible damaging of the deposited cells due to the formation of molecular chlorine. Furthermore, it was demonstrated that this technique is suitable to co-cultivate different cell types in a layered fashion. Subsequent to the electrically mediated anodic cell-protein deposition, cells were cultivated for up to 4 days and then characterized by vital fluorescence staining, methyl violet-staining and scanning electron microscopy. Cell-vitality was found to be dependent on the experimental setup; in this study non-vital cells were only observed, when sequentially depositing two different cell types. Finally, the coagulation mechanism was studied using HPLC, SDS-gel-chromatography and ATR/FTIR.

Animals↗

Intravenous mirtazapine is safe and effective in the treatment of depressed inpatients.

Mirtazapine is a third-generation antidepressant with a dual mode of action. The oral administration has been shown to be effective and safe in the treatment of depressed patients. In this multicenter naturalistic study, we assessed the safety, tolerability, and therapeutic efficacy of intravenously administered mirtazapine in 80 moderately to severely depressed inpatients during a treatment period of 14 days. We found a significant decrease of the Hamilton Depression Rating Scale total score compared to baseline. Side effects were mild and transient. Our data indicate that intravenous mirtazapine is an effective, safe and well-tolerated treatment for depressed inpatients.

Adolescent↗

Impact of familial risk factors on management and survival of early-onset breast cancer: a population-based study.

This population-based study evaluates the impact of a strong family history of breast cancer on management and survival of women with early-onset disease. We identified all breast cancer patients </=50 years, recorded between 1990 and 2001 at the Geneva familial breast cancer registry. We compared patients at high familial risk and low familial risk in terms of tumour characteristics, method of detection, treatment, survival and breast cancer mortality risk. Compared to patients at low familial risk (n=575), those at high familial risk (n=58) received significantly more often systemic therapy, especially for node-negative or receptor-positive disease. Five-year disease-specific survival rates of patients at high vs low familial risk were 86 and 90%, respectively. After adjustment, there was no difference in breast cancer mortality in general. A strong family history nonsignificantly increased breast cancer mortality in patients </=40 years (adjusted hazard ratio (HR) 4.0, 95% CI 0.8-19.7) and in patients treated without chemotherapy (adjusted HR 2.7, 95% CI 0.6-12.5). A strong family history of breast cancer is associated with an increased use of systemic therapy in early-onset patients. Although a strong family history does not seem to affect survival in general, it may impair survival of very young patients and patients treated without adjuvant chemotherapy. Owing to the limited number of patients in this study, these results should be used only to generate hypotheses.

Adult↗

Highly demanding resistive vibration exercise program is tolerated during 56 days of strict bed-rest.

Several studies have tried to find countermeasures against musculoskeletal de-conditioning during bed-rest, but none of them yielded decisive results. We hypothesised that resistive vibration exercise (RVE) might be a suitable training modality. We have therefore carried out a bed-rest study to evaluate its feasibility and efficacy during 56 days of bed-rest. Twenty healthy male volunteers aged 24 to 43 years were recruited and, after medical check-ups, randomised to a non-exercising control (Ctrl) group or a group that performed RVE 11 times per week. Strict bed-rest was controlled by video surveillance. The diet was controlled. RVE was performed in supine position, with a static force component of about twice the body weight and a smaller dynamic force component. RVE comprised four different units (squats, heel raises, toe raises, kicks), each of which lasted 60 - 100 seconds. Pre and post exercise levels of lactate were measured once weekly. Body weight was measured daily on a bed scale. Pain questionnaires were obtained in regular intervals during and after the bed-rest. Vibration frequency was set to 19 Hz at the beginning and progressed to 25.9 Hz (SD 1.9) at the end of the study, suggesting that the dynamic force component increased by 90 %. The maximum sustainable exercise time for squat exercise increased from 86 s (SD 21) on day 11 of the BR to 176 s (SD 73) on day 53 (p = 0.006). On the same days, post-exercise lactate levels increased from 6.9 mmol/l (SD2.3) to 9.2 mmol/l (SD 3.5, p = 0.01). On average, body weight was unchanged in both groups during bed-rest, but single individuals in both groups depicted significant weight changes ranging from - 10 % to + 10 % (p < 0.001). Lower limb pain was more frequent during bed-rest in the RVE subjects than in Ctrl (p = 0.035). During early recovery, subjects of both groups suffered from muscle pain to a comparable extent, but foot pain was more common in Ctrl than in RVE (p = 0.013 for plantar pain, p = 0.074 for dorsal foot pain). Our results indicate that RVE is feasible twice daily during bed-rest in young healthy males, provided that one afternoon and one entire day per week are free. Exercise progression, mainly by progression of vibration frequency, yielded increases in maximum sustainable exercise time and blood lactate. In conclusion, RVE as performed in this study, appears to be safe.

Adult↗

Short-term human chondrocyte culturing on oriented collagen coated gelatine scaffolds for cartilage replacement.

The biological, biochemical, mechanical, and structural properties of artificial scaffolds for tissue engineering are known to be of great importance. Therefore, in this study a hydrogel derived scaffold with biomechanical and structural properties similar to native articular cartilage was synthesized. The gelatine-based hydrogel was processed by freeze-structuring, structuring by electrochemical water-decomposition, freeze-drying and chemical fixation resulting in a defined scaffold-structure. By electron microscopy a perpendicular pore-channel structure was verified with channel diameters between 30 microm and 70 microm. Mechanical testing showed mechanical properties similar to native cartilage. Human chondrocytes from biopsy samples were cultivated on these hydrogel scaffolds for three days. Two different cell densities (1.2 x 10(6) cells/cm3 and 12.0 x 10(6) cells/cm3) were used for cultivation. Histology of the cell seeded artificial scaffolds demonstrated vital cells that are widely distributed within the scaffold and mimic a columnar arrangement.

Cartilage↗

Culture of haematopoietic cells in a 3-D bioreactor made of Al2O3 or apatite foam.

Foams of Al2O3 and apatite ceramics with interconnecting pores were produced using a new technique. The surfaces of the ceramics served as substrates for the culture of human peripheral and bone marrow derived stem cells. Up to 27 days the cells were kept in culture where they proliferated and developed into different morphologies consistent with bone marrow cell lines.

Aluminum Oxide↗

Development of a model food for microwave processing and the prediction of its physical properties.

Although microwave processes in the food industry such as microwave pasteurisation or microwave drying are already in use, most of their optimisation is still based on trial-and-error. To model these processes, knowledge of different physical properties of the food material is indispensable. In order to guarantee constant product properties a model food was developed imitating real food properties and showing physical and microbial stability over several months. In this manuscript the prediction of these physical properties and the comparison of the model food with a real food will be shown.

Computer Simulation↗

The quality of human skin xenografts on SCID mice: a noninvasive bioengineering approach.

BACKGROUND: Animal models are important tools for studies in skin physiology and pathophysiology. Due to substantial differences in skin characteristics such as thickness and number of adnexa, the results of animal studies cannot always be directly transferred to the human situation. Therefore, transplantation of human skin on to SCID (severe combined immunodeficiency) mice might offer a promising tool to perform studies in viable human skin without the direct need for human volunteers. OBJECTIVES: To characterize the physiological and anatomical changes of a human skin transplant on a SCID animal host. METHODS: In this study human skin was transplanted on to 32 SCID mice and followed for 6 months. Barrier function was assessed by transepidermal water loss (TEWL; tewametry) and moisture content of the stratum corneum was studied by measurement of electrical capacitance (corneometry). RESULTS: The results showed considerable deviations of TEWL values and skin hydration between the grafts and human skin in vivo. The human skin showed epidermal hyperkeratosis and moderate sclerosis of the corium 4 and 6 months after transplantation on to SCID mice. CONCLUSIONS: Our results indicate that human skin does not completely preserve its physiological and morphological properties after transplantation on to SCID mice. Therefore, results from experiments using this model system need to be discussed cautiously.

Animals↗

Content-based image retrieval in medical applications.

OBJECTIVES: To develop a general structure for semantic image analysis that is suitable for content-based image retrieval in medical applications and an architecture for its efficient implementation. METHODS: Stepwise content analysis of medical images results in six layers of information modeling incorporating medical expert knowledge (raw data layer, registered data layer, feature layer, scheme layer, object layer, knowledge layer). A reference database with 10,000 images categorized according to the image modality, orientation, body region, and biological system is used. By means of prototypes in each category, identification of objects and their geometrical or temporal relationships are handled in the object and the knowledge layer, respectively. A distributed system designed with only three core elements is implemented: (i) the central database holds program sources, processing scheme descriptions, images, features, and administrative information about the workstation cluster; (ii) the scheduler balances distributed computing; and (iii) the web server provides graphical user interfaces for data entry and retrieval, which can be easily adapted to a variety of applications for content-based image retrieval in medicine. RESULTS: Leaving-one-out experiments were distributed by the scheduler and controlled via corresponding job lists offering transparency regarding the viewpoints of a distributed system and the user. The proposed architecture is suitable for content-based image retrieval in medical applications. It improves current picture archiving and communication systems that still rely on alphanumerical descriptions, which are insufficient for image retrieval of high recall and precision.

Databases as Topic↗

Further characterization of IgE-binding antigens from guinea pig hair as new members of the lipocalin family.

BACKGROUND: Guinea pigs are important sources of inhalant allergens in home and working environments. However, little is known about the molecular characteristics and the relevant epitopes of guinea pig allergens. Recently, several allergens have been identified in hair extract and urine, and the major allergen Cav p 1 (20 kDa) has been characterized. OBJECTIVE: The aim of the present study was to isolate and to characterize a further major allergen from guinea pig hair with 17 kDa. METHODS: Guinea pig hair extract was fractionated using anion exchange chromatography and reverse-phase high performance liquid chromatography. Analyses were carried out by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, 2D-PAGE, immunoblotting, immunoblot inhibition, glycoprotein detection, and N-terminal amino acid sequencing. RESULTS: The nonglycosylated 17 kDa allergen, which was named Cav p 2, was purified to homogeneity. On the basis its 15 N-terminal residues, there was 69% identity with a sequence of Bos d 2, an allergenic protein from cow dander belonging to the lipocalin family. The 2D-immunoblotting analyses of guinea pig hair extract demonstrated that Cav p 2 and Cav p 1, contained several isoforms with pI values ranging from 3.6 to 5.3. The 2D-immunoblot inhibition disclosed cross-reactive IgE epitopes on the allergens Cav p 2 and Cav p 1. Furthermore, Cav p 1 can form both monomers (20 kDa) and dimers (40-42 kDa). CONCLUSION: These studies provide important information on the isoallergen character of two relevant guinea pig allergens Cav p 1 and Cav p 2 as well as on their cross-reactive properties.

Allergens↗

Regional alterations in fiber type distribution, capillary density, and blood flow after lower jaw sagittal advancement in pig masticatory muscles.

Muscular remodeling is known to be a prerequisite for permanent correction of mandibular-maxillary malocclusion. The objective of this study was to clarify if an increase in type I fiber number is accompanied by an increased capillary density and improved muscular blood flow. Juvenile pigs received build-ups on the molars, which induced a protrusion of 7.6 + 1.5 mm. After 4 weeks of treatment, chronic lower jaw protrusion induced a marked muscle blood flow increase in the anterior and medial regions of the superficial part of the masseter and in the medial pterygoid muscle (P < 0.05). Furthermore, an increase in capillary density and in the amount of type I fibers was found in all regions of masticatory muscles with an increased muscle blood flow (P < 0.05). Finally, the capillary-to-fiber ratio increased (P < 0.05). Muscle blood flow and capillary density showed a strong linear correlation (r = 0.89, P < 0.01). These changes suggest a complex muscle adaptation for long-term, fatigue-resistant activity during the early corrective period of mandibular-maxillary malocclusion treatment.

Animals↗

Purification and partial characterization of the major allergen, Cav p 1, from guinea pig Cavia porcellus.

BACKGROUND: Allergic reaction to guinea pig has been recognized as a problem in domestic settings and work environments for many years. Until recently, limited information was available on the properties of guinea pig allergen(s). In this study the major allergen Cav p 1 was characterized and the N-terminal amino-acid sequence was determined. METHODS AND RESULTS: Sera from 40 patients with IgE-mediated allergy to guinea pigs were investigated by means of immunoblotting using extracts prepared from guinea pig hair and urine. Three major allergens were identified within both sources with molecular weights (MW) of 8 kDa, 17 kDa and 20 kDa, respectively. From aqueous hair extracts the 20 kDa allergen (Cav p 1) was purified to homogeneity by anion exchange chromatography and reverse-phase HPLC and the N-terminal amino-acid sequence was determined. On the basis of the 15 residues, 57% identity was obtained from computer search with a sub-sequence of MUP (major urinary protein), a member of the lipocalin superfamily. Allergenic relationships among guinea pig allergens derived from various sources (hair and urine) or different animal species (mouse, rat, cat) were studied by ELISA inhibition assays. Neither urine of mouse, rat and cat, nor hair extracts of rat and cat produced appreciable inhibitions in guinea pig ELISA. CONCLUSION: Although the physicochemical characteristics of isolated Cav p 1 are very similar to those for other rodent allergens and furthermore partial sequence identity with Mus m 1 was found, it is clearly shown here to be an immunologically independent major allergen.

Allergens↗

[Percutaneous sclerotherapy of a varicocele with atypical retrograde flow using a double-balloon occlusion technique].

OBJECTIVE: To perform a double-balloon occlusion for selective sclerosis of the internal spermatic vein in a varicocele with atypical retrograde flow. METHOD: In a 19-year-old man with a primary varicocele, phlebography demonstrated an 8-mm-wide internal spermatic vein with parallel collaterals and marked reflux of the contrast agent in the supine position. A single balloon occlusion could not prevent rapid wash-out of contrast material via collateral veins. Subsequently, two 8-mm balloon-catheters were sequentially inserted into the internal spermatic vein. After inflation of both balloons, the sclerosing agent was administered through the proximal catheter into the balloon-occluded venous segment. RESULT: Percutaneous sclerotherapy using the double-balloon technique achieved complete stasis inside the ectatic and retrograde perfused spermatic vein including its major parallel collaterals. CONCLUSION: In primary varicocele with strong spontaneous reflux and complicated flow pattern of the collateral veins, the double-balloon occlusion technique can achieve high local concentration of the sclerosing agent at optimal position and without wash-out effects.

Adult↗

Lung perfusion affects preload assessment and lung water calculation with the transpulmonary double indicator method.

OBJECTIVES: The transpulmonary double indicator method uses intra- and extravascular indicators to calculate cardiac output, intrathoracic blood volume, global end-diastolic volume, and extravascular lung water content. Since lung perfusion may be of importance during these measurements, we studied the effects of pulmonary blood flow occlusion on measurements obtained with this method. SETTING: Experimental animal facility of a University department. METHODS AND INTERVENTIONS: In seven pigs, the branch of the pulmonary artery perfusing the lower and middle lobe of the right lung was occluded. Measurements before, during, and after the occlusion were made with a pulmonary artery catheter and a commonly used transpulmonary double indicator catheter and device. MEASUREMENTS AND RESULTS: Occlusion of the right lower and middle lobe branch of the pulmonary artery increased mean pulmonary pressure (before occlusion: 24+/-1, during occlusion: 32+/-2, after reopening 25+/-1 mmHg; P<0.05), increased right ventricular end-diastolic volume (172+/-34, 209+/-21, 174+/-32 ml, respectively; P<0.05), decreased intrathoracic blood volume (998+/-39, 894+/-48, 1006+/-49 ml, respectively; P<0.05), and decreased extravascular lung water (7.2+/-0.5, 4.2+/-0.4, 6.9+/-0.4 ml/kg, respectively; P<0.05) without causing significant changes in cardiac output. All changes were reversible upon reopening the vessel. CONCLUSIONS: These data show that the transpulmonary double indicator method may underestimate extravascular lung water and right ventricular preload when the perfusion to parts of the lung is obstructed.

Animals↗

Non-linear changes of electrocortical activity after antenatal betamethasone treatment in fetal sheep.

We determined the effects of betamethasone on the fetal sheep electrocorticogram (ECoG) using linear (power spectral) and non-linear analysis. For non-linear analysis we used an algorithm based on the Wolf algorithm for the estimation of the leading Lyapunov exponent which calculates a prediction error based on the course of the time series in the phase space. A high prediction error stands for low predictibility or low regularity and vice versa. After 48 h of baseline recordings, vehicle (n = 6) or betamethasone (n = 7) at 10 microg h(-1) was infused over 48 h to the sheep fetus at 128 days gestational age (0.87 of gestation). ECoG spectral analysis revealed no difference in power spectrum between vehicle- and betamethasone-treated fetuses. The prediction error of the ECoG during REM sleep was higher than during non-REM or quiet sleep in both groups (P < 0.0001) revealing lower causality of brain activity during REM sleep. During REM sleep, prediction error significantly decreased 18-24 h after onset of betamethasone treatment (P < 0.05) and returned to baseline values within the following 24 h of continued betamethasone treatment. No ECoG changes were found during quiet sleep. Non-linear ECoG changes during metabolically active REM sleep accompanied the previously described decrease in cerebral blood flow. These results suggest that betamethasone in doses used in perinatal medicine acutely alters complex neuronal activity.

Algorithms↗

Effect of antenatal betamethasone treatment on microtubule-associated proteins MAP1B and MAP2 in fetal sheep.

Betamethasone has been used extensively to accelerate fetal lung maturation, yet little is known of its effects on neuronal morphogenesis in the developing fetus. Microtubule-associated proteins (MAPs) are a diverse family of cytoskeletal proteins that are important for brain development and the maintenance of neuroarchitecture. Vehicle (n = 7) or betamethasone (10 ug h-1, n = 7) was infused I.V. to fetal sheep over 48 h beginning at 0.87 of gestation (128 days of gestation), producing fetal plasma betamethasone concentrations resembling those to which the human fetus is exposed during antenatal glucocorticoid therapy. Paraffin sections of the left hemisphere were stained with monoclonal antibodies against MAP1B and the MAP2 isoforms MAP2a,b,c and MAP2a,b. The level of the juvenile isoform MAP2c was determined by comparison of the two MAP2 immunostainings. We were able to detect MAP1B and MAP2 immunoreactivity (IR) in the fetal sheep brain. MAP2c was the major MAP2, constituting 90.2 % of the total MAPBetamethasone exposure diminished MAP1B IR in the frontal cortex and caudate putamen (P < 0.05) but not in the hippocampus. A decrease of MAP2 IR was found in the frontal cortex, hippocampus and caudate putamen (P < 0.05). Loss of MAP2 IR was mainly due to the loss of MAP2c IR. Haematoxylin-eosin staining did not demonstrate irreversible neuronal damage. Regional cerebral blood flow determined using coloured microspheres was significantly decreased by 28 % in the frontal cortex and by 36 % in the caudate putamen but not in the hippocampus 24 h after the onset of betamethasone exposure (P < 0.05). The loss of MAP1B and MAP2a,b,c IR showed a significant correlation to the cerebral blood flow decrease only in the frontal cortex (P < 0.05). These data suggest that mechanisms other than metabolic insufficiency caused by the decreased cerebral blood flow may contribute to the loss of MAPs. The results suggest that clinical doses of betamethasone may have acute effects on cytoskeletal proteins in the fetal brain.

Animals↗