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Biomedical subjects

M Schwab

Publications and source records attributed to M Schwab.

At least 127 records · Page 7Linked to original sources
PubMed1998

Vestibular function in the fetal sheep.

Little is known about the functional development of the vestibular system before birth. The purpose of this study was to determine whether vestibular response to caloric stimulation could be elicited in the fetal sheep in utero. Late gestational fetal sheep (n = 6) were instrumented through a midline hysterotomy. Copper caloric probes were inserted into the right bulla and beneath the left facial skin. Electrodes were placed in the skull for monitoring of electro-ocular activity. At least 3 days after surgery the probes were irrigated with water (100 ml/minute) at body temperature, 46 degrees C, and 6 degrees C. Cold water infusion of the bulla consistently produced well-recognized, slow-phase deviations followed by saccades directed contralaterally, findings consistent with vestibular nystagmus. The direction of the response reversed with warm water irrigation. The response was absent with irrigation at fetal body temperature. Only random eye movements were observed in response to caloric stimulation of the facial skin, regardless of water temperature. These results demonstrate that the sheep vestibular system is functioning prenatally. The importance of vestibular function for normal fetal brain maturation may be revealed in future studies using this animal model.

Animals↗
PubMed1998

Mild hypothermia prevents the occurrence of cytotoxic brain edema in rats.

Hypothermia maintains the impermeability of the blood-brain barrier to proteins and, therefore, presumably the development of vasogenic brain edema after brain ischemia. We intended to determine whether mild hypothermia would have a protective effect against cytotoxic brain edema, the early stage of ischemic brain edema. Two groups of Wistar rats (37 degrees C and 35 degrees C body temperature) were subjected to 6 h of moderate decrease of cerebral blood flow (CBF) by means of permanent bilateral carotid artery ligation, and compared to a third group of unaffected animals. Carotid artery ligation induced a local cerebral blood flow (LCBF) reduction to 50-80% of baseline values. LCBF in the frontal cortex was restored to a higher level in hypothermic animals than in normothermic ones (P < 0.05). In normothermic animals, an increase of brain water content was detected in the frontoparietal and occipital cortex as well as in the hippocampus (P < 0.05), but only in one region of the frontoparietal cortex in hypothermic animals. The impermeability of the blood-brain barrier to proteins was shown by the absence of staining with Evans blue as an indicator of vasogenic brain edema. We conclude that mild hypothermia offers protection against the development of cytotoxic brain edema.

Animals↗
PubMed1998

The evolution of a German teleradiology system.

This paper describes the evolution of a german teleradiology system. The development started from simple image file transfer, continued with a dedicated teleradiology system and ended up with a general radiology workstation with teleradiology features. The main features, advantages and drawbacks of the different generations are described. The own developments are compared with developments at other places. The influence by standards is also included in this investigation. The latest systems are mainly used by the radiologists and the image transfer for scientific cooperation is nowadays just one of several application fields of teleradiology.

Germany↗
PubMed1997

Yeast Hct1 is a regulator of Clb2 cyclin proteolysis.

Stage-specific proteolysis of mitotic cyclins is fundamental to eukaryotic cell cycle regulation. We found that yeast Hct1, a conserved protein of eukaryotes, is a necessary and rate-limiting component of this proteolysis pathway. In hct1 mutants, the mitotic cyclin Clb2 is highly stabilized and inappropriately induces DNA replication, while G1 cyclins and other proteolytic substrates remain short-lived. Viability of hct1 mutants depends on SIC1. This and further results suggest that inhibition of cyclin-dependent kinases may compensate for defects in cyclin proteolysis. Remarkably, elevated levels of Hct1 ectopically activate destruction box- and Cdc23-dependent degradation of Clb2 and cause phenotypic effects characteristic for a depletion of M-phase cyclins. Hct1 and the related Cdc20 may function as substrate-specific regulators of proteolysis during mitosis.

Amino Acid Sequence↗
PubMed1997

In vivo regulation of single copy and amplified N-myc in human neuroblastoma cells.

Amplification with subsequent overexpression of N-myc is a recurrent genomic alteration of neuroblastoma cells. DMS-in-vivo-footprinting of the basal promoter of the human N-myc gene (positions -221 to +21) revealed three changes in promoter architecture that are clustered in a 50 bp region and included (1) protein binding to two overlapping E2F-sites, (2) extreme hypersensitivity of guanine - 159, and (3) a short stretch of single stranded DNA with a single protected guanine. While in transient assays the basal promoter activated gene expression in all cell lines analysed, the changes at the endogenous promoter were restricted to neuroblastoma cells with strong N-myc expression. The hypersensitivity of guanine -159 could result from protein binding to a flanking, evolutionary conserved 5'-CCTCCC-3'-element, referred to as CT-box, that was bound in vitro in a Zn2+-requiring manner by a protein from nuclear extracts of neuroblastoma cells. Four copies of the CT-box in front of an N-myc minimal promoter (-60 to + 18) activated expression of a reporter gene in transient transfections whereas four copies of the mutant element did not. Our data add N-myc to a growing list of mammalian genes with CT-boxes that bind proteins in a Zn2+-dependent manner. Moreover, the data suggest that a common mechanism controls N-myc expression in neuroblastomas irrespective of N-myc copy number, and that in cell lines with amplification all gene copies contribute to N-myc expression.

Animals↗
PubMed1997

The distribution of normal brain water content in Wistar rats and its increase due to ischemia.

The aim of this study was to describe the normal distribution of the water content in several regions of the rat brain and furthermore to determine if global ischemia results in a variable increase in water content in these regions. Water content was determined in 40 regions; in 8 unaffected brains by gravimetry and in 9 unaffected brains by estimation of the wet/dry weight ratio. In addition, 6 rats underwent 6 h of moderate global brain ischemia in order to evaluate the sensitivity of the investigated brain areas to develop a cytotoxic brain edema. The impermeability of the blood-brain barrier to proteins was evaluated by staining with Evans blue. Physiological differences in water content between the several brain regions ranged from 72.57 +/- 0.77% (mean +/- S.D.) in the medulla oblongata to 84.83 +/- 0.52% in the hypothalamus. Generally, the water content of the grey matter was higher than that of the white matter and increased from the frontal to the occipital and from the parietal to the basal cortex. Even adjacent cortical regions showed differences in the amount of brain water of up to 3.41%. In the ischemic animals, the impermeability of the blood-brain barrier to proteins was not compromised, but an increase in the amount of brain water was found in the frontoparietal cortex of 1.17 +/- 0.37% and hippocampus of 1.49 +/- 0.39% (P < 0.05). This ischemic increase in the brain water content was small in comparison to the normal variance in regional brain water content. Similar results were obtained by determining the wet/dry weight ratio and by gravimetry. Gravimetry led to more consistent results. In conclusion, the study shows great differences in normal water content between the several brain areas in comparison to an only slight increase of water content due to the development of cytotoxic brain edema. The determination of an early state of an increased brain water content requires an adequate and differentiated measurement of different brain areas. The gravimetry fulfills this demand.

Animals↗
PubMed1997

[Hormone inactive neuroendocrine tumors of the pancreas].

During the past 10 years (1987-1996), 842 laparotomies were performed for pancreatic or periampullary neoplasms; in 25 patients (2.9%) a neuroendocrine tumor was diagnosed. In 19 of these 25 patients (76%) a non-functioning endocrine tumor and in 6 patients (24%) a hormone-active tumor (four insulinoma, one gastrinoma, one VIPoma) was found. Of 19 non-functioning neuroendocrine tumors, 14 were malignant. The resection rate of these malignant tumors was 78.6% (11 of 14; 3 resections were palliative); in comparison, the resection rate of ductal pancreatic carcinoma in our hospital was 28.1%. The probability of 5-year survival amounts to 73% after surgical resection in malignant endocrine tumors and to 19% in ductal pancreatic carcinoma (including palliative resections). As it is not always clear whether non-functioning endocrine tumors are benign or malignant, oncological resection is recommended. Adjuvant chemotherapy seems not to be necessary.

Adult↗
PubMed1997

Electrocortical and heart rate response during vibroacoustic stimulation in fetal sheep.

OBJECTIVE: Our purpose was to study effects of vibroacoustic stimuli on electrocortical activity and heart rate changes in fetal sheep in utero. STUDY DESIGN: Seven chronically instrumented near-term fetal sheep were repeatedly stimulated by an electronic artificial larynx for 32 seconds during periods of rapid-eye-movement and non-rapid-eye-movement sleep. Responses to vibroacoustic stimulation were obtained by spectral analysis of the electrocorticogram (fast Fourier transform) and by assessment of changes in fetal heart rate and fetal heart rate variability. RESULTS: During non-rapid-eye-movement sleep vibroacoustic stimulation led to electrocorticogram desynchronization that consisted of a marked reduction of delta and theta band power (p < 0.05). A concomitant fetal heart rate decrease and fetal heart rate variability increase were also noted (p < 0.05). During rapid-eye-movement sleep vibroacoustic stimulation induced a significant increase in alpha and beta band power (p < 0.05) and a slight deviation in basal fetal heart rate and fetal heart rate variability (p < 0.05). CONCLUSION: Vibroacoustic stimulation of fetal sheep provokes reproducible changes in fetal electrocortical activity and heart rate patterns. These changes, which are not easily identifiable in gross polygraphic assessments of the fetal behavioral state, are indicative of fetal arousal.

Acoustic Stimulation↗
PubMed1997

Experiences with the german teleradiology system MEDICUS.

This paper introduces the teleradiology system, MEDICUS, which has been developed at the Deutsches Krebsforschungszentrum (German Cancer Research Center) in Heidelberg, Germany. The system is designed to work on ISDN lines as well as in a local area network. The global software architecture is explained in the article. Special attention has been given to the design of the user interface and data security, integrity and authentication. The software has been evaluated in a German field test at 13 radiology departments in university clinics, small hospitals, private practices and research institutes. More than 30 thousand images have been transmitted using this system during a 9 month period. Realized application scenarios are: in-house communication, image and report delivery to referring hospitals, remote reporting, radiotherapy treatment planning and research cooperation. Experience has shown that the system is easy to use and saves time. It obviates the need for patient transport and reduces film costs. Experiences of individuals while using the system during the field test helped define the functionality of the second generation teleradiology system which is even more flexible and is also available as a commercial product.

Computer Communication Networks↗
PubMed1997

Morphofunctional effects of moderate forebrain ischemia combined with short-term hypoxia in rats--protective effects of Cerebrolysin.

Morphofunctional effects of combined moderate forebrain ischemia due to permanent bilateral carotid artery ligation and short-term systemic hypoxia in rats were investigated. Moreover, a putative effect of brain protection by Cerebrolysin (Cerebrolysin, EBEWE, Austria), a brain tissue hydrolysate containing a mixture of 85% free amino acids and 15% small peptides (MW < 10,000), was studied. Eighty-seven adult Wistar rats (24 Cerebrolysin treated and 63 controls) were subjected to chronic moderate forebrain ischemia by permanent bilateral carotid artery ligation for 7 days. Twenty-four hours after the onset of ischemia, 56 of them underwent an additional hypoxic hypoxia (FiO2 = 0.08) of 15 min. A first group (19 out of 56 animals) received Cerebrolysin (every dose 2.5 ml/kg body weight s.c.) after ligation, after hypoxia and then daily. A second group (6 out of 56 animals) received an equal volume of physiological saline after ligation and Cerebrolysin the first time after hypoxia and then once a day. An untreated control group (31 out 56 animals) received physiological saline. Changes in behavior were scored and electrophysiological activity was quantified by spectral ECoG analysis before carotid artery ligation, before and after hypoxia, and once a day during the following 7 days. On the 7th day after hypoxia, the animals were sacrificed and the grade of histological damage was quantified by morphometry. After permanent carotid artery ligation, 20 out of 63 (31.7%) untreated control animals died within 24 h but only 4 out of 20 (16.7%) Cerebrolysin treated animals. However, Cerebrolysin had not detectable effect on mortality after the additional acute hypoxia. Within 24 h after hypoxia, ECoG power of the higher frequency ranges remained low (p < 0.05). Surviving animals showed a significantly higher ECoG power during and 15 min after hypoxia than those animals that died within 48 h after hypoxia (p < 0.05). All animals showed reduced behavioral activity (p < 0.01) 20 min after hypoxia, however, basal reflex responses were not altered. The major patterns of neuronal damage were coagulation necrosis and general sponginess of the neuropil which is a sign of brain edema. These changes occurred predominantly within the superolateral convexities of the parietal cortex, in the entorhinal and in the piriform cortex as well as in the CA1 and CA4 region and in the dentate gyrus of the hippocampus. The striatum and the origin nuclei of the brain nerves were also affected. We did not observe a relationship between behavior, ECoG depression and the extent of morphological damage after hypoxia nor did we find any protective effects of Cerebrolysin on these parameters. Rather it is suggested that the degree of ECoG depression immediately after hypoxic hypoxia could be a predictor for prognosis of animal survival. Cerebrolysin reduced the amount of early mortality which was caused by moderate global forebrain ischemia. However, no protective influences of the amount of brain tissue damage could be shown.

Amino Acids↗
PubMed1997

Physiological effects and brain protection by hypothermia and cerebrolysin after moderate forebrain ischemia in rats.

The "therapeutic window" of neuroprotective intervention due to hypoxic-ischemic brain injuries are initial disturbances of the neuronal function in regions of only moderate decrease of local cerebral blood flow (ICBF). Because of limited effects of single therapeutic principles therapeutic combinations should be tested. Neuroprotective effects of mild hypothermia and the nootropic drug Cerebrolysin (Cerebrolysin, EBEWE, Austria) on ICBF and development of brain edema were used. Four groups of adult Wistar rats (untreated and Cerebrolysin treated animals with 35 degrees C and 37 degrees C rectal temperature) were subjected to moderate forebrain ischemia by permanent bilateral carotid artery ligation for 6 h. The ICBF was measured continuously in the frontal and the occipital cortex by a 2-channel Laser Doppler flowmeter. The ECoG was derived from 4 ECoG leads above the frontal and occipital cortex and quantified by spectral analysis. Six hours after the onset of ischemia, the function of the blood-brain barrier to proteins was determined by staining with Evans Blue, the animals were sacrificed and the brain water content was estimated by gravimetry. Permanent bilateral carotid artery ligation led to an abrupt ICBF reduction to between 40-50% of baseline levels. Within a few minutes, however, the ICBF increased again to 50-80% of the baseline. The reduced spectral band power of the ECoG was correlated with the decreased ICBF values (p < 0.05) that indirectly indicated changes in the energy state of the neurons (p < 0.05). Changes in the ECoG appeared only with a delay of approximately 4 sec after the onset of ICBF reduction. Six hours after the onset of ischemia, a cytotoxic brain edema was shown in the frontoparietal cortex and hippocampus. Reducing the temperature by 2 degrees C diminished the decrease in ICBF between 10 min and 2 h after the onset of ischemia (p < 0.05). This effect was noted in the frontal but not in the occipital cortex. Furthermore, mild hypothermia prevented the loss of ECoG spectral power in the beta, alpha and theta bands (p < 0.05) as well as the development of cytotoxic brain edema. Cerebrolysin prevented the development of brain edema, too, both under normo- and hypothermic conditions. The ICBF was restored to higher levels in the occipital cortex in comparison both to the normothermic Cerebrolysin treated and hypothermic untreated rats (p < 0.05). This effect of Cerebrolysin was associated with only slight changes in ECoG, indicating that the neuronal activity state and the energy supply was obviously not decisively influenced. In conclusion, moderate ICBF reduction in rats to about 50-80% of baseline values was detectable in the ECoG by using spectral analysis. This reduction led to the development of cytotoxic brain edema in rats within 6 h. Thus, hypothermia prevents the development of cytotoxic brain edema. Cerebrolysin enhanced the effects of hypothermia on ICBF reduction and on the development of brain edema.

Amino Acids↗
PubMed1997

The current contribution of molecular factors to risk estimation in neuroblastoma patients.

The association of molecular characteristics with prognosis has been reported, but not their relationship with each other and their impact in the context of known clinical risk factors. In this study, data of 1249 consecutive intent-to-treat-neuroblastoma patients with more than 1 year follow-up were examined by multivariate analysis using loglinear and Cox proportional hazard regression models on a stage-related basis (stages 1-3: 600, 4S: 116, 4: 533). In a first step, risk factors were identified from 18 selected clinical variables, and risk groups defined. The second step investigated whether molecular characteristics (MYCN, LOH 1p, del 1p, CD44, N-ras, NGF-R, bcl-2, APO-1 (CD95)) contributed additional prognostic information to the model. The loglinear model demonstrated several interactions between clinical factors. By the Cox regression model, seven independent clinical risk factors were found for stages 1-3, seven for stage 4 and two for stage 4S. By subsequent introduction of all molecular variables, MYCN amplification only added significant prognostic information to the clinical factors in localised and stage 4 neuroblastoma. The models allowed the definition of risk groups for stages 1-3 patients by age (e beta = 5.09) and MYCN (e beta = 4.26), for stage 4 by MYCN (e beta = 2.78) and number of symptoms (e beta = 2.44) and for stage 4S by platelet count (e beta = 3.91) and general condition (e beta = 2.99). Molecular factors and in particular MYCN contribute significantly to risk estimation. In conjunction with clinical factors, they are powerful tools to define risk groups in neuroblastoma.

Adolescent↗
PubMed1997

Patterns of oncogene activation in human neuroblastoma cells.

Human neuroblastoma is the most frequent solid tumor in children. Recent studies suggest that a multiplicity of genomic alterations contributes to neuroblastoma, the most frequent and well studied being deletion of the short arm of chromosome 1 and amplification of N-MYC. We here present and discuss different patterns of oncogene activation including, amplification of N-MYC, duplication of N-MYC and amplification of MDM2.

Gene Expression Regulation, Neoplastic↗
PubMed1997

Use of aminoglycosides in elderly patients. Pharmacokinetic and clinical considerations.

Aminoglycosides still represent a mainstay in the treatment of serious infections caused by Gram-negative bacilli in elderly patients. The aging process is accompanied by various physiological changes (e.g. alterations in body composition, impairments in certain organ functions), which may affect drug disposition and, subsequently, drug action. For aminoglycosides that are eliminated by the renal route, kidney function is the key parameter that should be taken into account when dosage regimens are calculated. Because there is a progressive decline in renal function with aging, the glomerular filtration rate should be estimated for each patient. Any change in creatinine clearance (CLCR) should result in a proportional correction of the dosage regimen. Such individualised dosage of aminoglycosides is particularly important because of their narrow therapeutic indices. There are no conclusive data which indicate that age per se affects the elimination of aminoglycoside antibiotics. Overdosage may result from overestimation of renal function if crude serum creatinine (SCr) levels are used as a guide. Nomograms for the relationship between SCr and CLCR have been developed. However, nomograms should be used with caution because substantial interindividual variability in the plasma concentration-clearance relationship is still observed. Therefore, the choice of a maintenance dose based on an assessment of renal function, which change rapidly, should always be considered as preliminary, and verification by serum concentration measurements is necessary. As a result, the use of aminoglycoside serum concentration monitoring during therapy as the most important guide for dosage adjustment is particularly important in the elderly, and is indispensable in conjunction with frequent assessment of renal function. Although a matter of debate, the value of serum concentration monitoring has been demonstrated. With traditional multiple daily dosage, monitoring peak and trough concentrations has been recommended. For once daily dosage, however, no guidelines relating to therapeutic and/or toxic concentrations are available yet. In the meantime, we recommend monitoring at least trough concentrations. Once daily administration of aminoglycosides has emerged as a new mode of treatment. Compared with multiple daily administration, once daily dosage may have a number of advantages, and many clinical trials comparing the efficacy or safety of both modes have shown either superiority or equivalence of the new mode in most indications. At present, however, no data from studies of once daily administration in young compared with elderly adults are available.

Aged↗