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Biomedical subjects

H Sauer

Publications and source records attributed to H Sauer.

At least 91 records · Page 5Linked to original sources

[New trends in the follow-up of malignant diseases].

For many of the frequent malignant diseases (e.g. breast cancer, lung cancer, gastrointestinal cancers and urological cancers--except germ cell tumors) there is no clear evidence (in the sense of "evidence-based medicine") for the efficacy of fixed schedules during follow-up using imaging or laboratory procedures. Intensive and expensive follow-up programs could be justified by proven results, e.g. a better chance of cure, a longer survival and/or a better quality of life. But unfortunately, such results are not available for most of the frequent tumors. The following criteria should lead every physician when guiding his patients through the follow-up period after the potentially curative treatment of a malignant disease: Every single diagnostic step must be backboned by a clear medical rationale. Alone the fact that technical investigations can be made easily and are available almost everywhere cannot be the rationale to perform these methods routinely. The wish of the patient alone, to have some technical applications, is not a plausible reason to perform it, unless there is a clear medical indication. The unfounded and private desire of the physician, that he should know some results (e.g. tumor markers), is in most cases, insufficient justification.

Follow-Up Studies↗

Impaired sensory processing in male patients with schizophrenia: a magnetoencephalographic study of auditory mismatch detection.

The generation of mismatch negativity (MMN) as a component of auditory evoked event-related brain potentials has been reported previously to be severely disturbed in patients with schizophrenia. In the present study, we extended these findings to magnetoencephalography and investigated the neuromagnetic mismatch field (MMNm) in 15 male schizophrenic inpatients as compared to 16 healthy male volunteers. A standard tone of 1000 Hz and three different types of mismatch (1050-Hz tone, 5000-Hz tone, tone omission) were employed within the same paradigm, each mismatch occurring with a 10% pseudorandom probability. After correction for eye artifacts, the mean global field power of the mismatch reaction was calculated. Mismatch generation in patients with schizophrenia proved to be significantly impaired for all three conditions. This result confirms the theory of impaired auditory information processing in patients with schizophrenia at the level of the primary auditory cortex. Deficient generation of MMNm probably represents an impaired generation and/or faster decay of the sensory memory trace on the basis of disturbed sensory processing in male patients with schizophrenia.

Adult↗

Frontal lobe in vivo (31)P-MRS reveals gender differences in healthy controls, not in schizophrenics.

Phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) has gained much interest in schizophrenia research in recent years since it allows the non-invasive measurement of high-energy phosphates and phospholipids in vivo. However, until now only differences in metabolite concentrations between certain brain areas of schizophrenic patients and healthy controls have been examined. We investigated the influence of gender on the concentrations of different phosphorus compounds. For this purpose, well-defined volumes in the frontal lobe of 32 healthy controls and 51 schizophrenic in-patients were examined with an image selected in vivo spectroscopy (ISIS) sequence on a whole-body scanner at 1.5 T. Healthy females exhibited increased values of inorganic phosphate (P(i)) and decreased values of phosphocreatine (PCr) in comparison to their male counterparts. In schizophrenic patients such gender differences were not present. Thus, the results can be interpreted in the sense that frontal energy demanding processes are enhanced in female compared to male healthy volunteers; schizophrenia seems to reduce these gender differences.

Adenosine Triphosphate↗

Detecting structural changes in whole brain based on nonlinear deformations-application to schizophrenia research.

This paper describes a new method for detecting structural brain differences based on the analysis of deformation fields. Deformations are obtained by an intensity-based nonlinear registration routine that transforms one brain onto another one. We present a general multivariate statistical approach to analyze deformation fields in different subjects. This method was applied to the brains of 85 schizophrenic patients and 75 healthy volunteers to examine whether low frequency deformations are sufficiently sensitive to detect regional deviations in the brains of both groups. We observed significant changes caused by volume reduction in brains of schizophrenics bilaterally in the thalamus and in the superior temporal gyrus. On the left side, the superior frontal gyrus and precentral gyrus are found to be changed, while on the right side, the middle frontal gyrus was altered. In addition, there were significant changes in the occipital lobe (left lingual gyrus) and in the left cerebellum. Volume enlargement in brains of schizophrenics was observed in the right putamen and in the adjacent white matter of the thalamic region. Our data suggest a disturbance in the nodes of a prefrontal-thalamic-cerebellar circuitry. This provides further support for the model of "cognitive dysmetria," which postulates a disruption in these nodes. We have demonstrated the application of deformation-based morphometry by detecting structural changes in the whole brain. This technique is fully automatic, thus allowing for the inclusion of large samples, with no user bias or a priori-defined regions of interest.

Adult↗

[Quality of life. Construct validation and the development of a modular system].

The construct Quality of Life (QoL) is investigated by metaanalysis of eight (inter)nationally validated questionnaires in a multicenter study. Data have been collected in a mentally healthy (n = 479), a depressed (n = 171) and a schizophrenic (n = 139) sample. Conventional psychometric criteria and a facet analytical methodology have been applied. The resulting questionnaire "Modular System for Quality of Life" (MSQoL) consists of a core module with 47 items (one "G-factor" and six subdimensions), which is sufficiently valid for all three samples. Additionally, there are four specific modules (demography, family, partnership, profession). No specific modules can be identified for the psychopathological subgroups. The validated radex structure for subjective QoL offers the opportunity for a cumulative research design and for adaptations to the actual setting.

Adolescent↗

Action potential propagation failures in long-term recordings from embryonic stem cell-derived cardiomyocytes in tissue culture.

Three-dimensional cell aggregates (embryoid bodies, EBs) containing clusters of spontaneously beating cardiomyocytes were derived from permanent mouse embryonic stem (ES) cells. Extracellular recordings of the population action potentials of cardiomyocyte clusters were made using permanently mounted silver wire electrodes and microelectrode arrays integrated into the bottom of the culture dish. These techniques allowed long-term recordings (for up to several weeks) from individual EBs under cell culture conditions. The normal electrical activity consisted of regular spiking with a frequency of 0.5-5 Hz. However, most EBs (87%) spontaneously developed temporary or persistent complex activity patterns because of intermittent block of action potential propagation at narrow pathways connecting larger beating areas. Similar propagation blocks could also be reversibly induced in regularly spiking EBs by nimodipine (NDP). In addition to a slowing of pacemaker activity, NDP (20-200 nM) induced a stepwise decrease of the action potential frequency at the recording site. Perforated patch-clamp recordings from enzymatically isolated ES-cell-derived cardiomyocytes showed that similar activity patterns do not occur at the single-cell level. We suggest that this novel approach may provide a useful tool for in vitro studies of chronotropy and phenomena of propagation failure similar to AV block.

Action Potentials↗

Redox-regulation of intrinsic prion expression in multicellular prostate tumor spheroids.

The cellular function of the intrinsic prion protein (PrPc) remains largely unknown. In the present study PrPc expression was investigated in multicellular prostate tumor spheroids and was correlated to the intracellular redox state as evaluated using the fluorescent dye 2'7'-dichlorodihydrofluorescein diacetate (H2DCFDA). In small tumor spheroids (diameter 100 +/- 20 microm) reactive oxygen species (ROS) levels were increased as compared with large (diameter 250 +/- 50 microm) spheroids. ROS generation was mediated by the mitochondrial respiratory chain and a NADPH oxidaselike enzyme, because carbonylcyanide-m-chlorophenylhydrazone (CCCP), rotenone, and diphenylene iodonium chloride (DPI) significantly reduced ROS levels. The elevated ROS were correlated to an increased expression of PrPc, Cu/Zn superoxide dismutase (SOD-1), and catalase in small as compared with large spheroids. In large tumor spheroids, PrPc was predominantly expressed in the peripheral cell layers and colocalized with SOD-1 and catalase. Raising intracellular ROS in large tumor spheroids by hydrogen peroxide, menadione, buthionine sulfoximine (BSO), and incubation in glutamine-reduced medium increased PrPc expression. In small spheroids PrPc was downregulated after incubation with the radical scavengers dehydroascorbate (DHA) and vitamin E. Our data indicate that PrPc expression in tumor spheroids is related to the intracellular redox state and may participate in antioxidative defense.

Antioxidants↗

Decreased frontal activation in schizophrenics during stimulation with the continuous performance test--a functional magnetic resonance imaging study.

The Continuous Performance Test (CPT) has become an essential constituent of the neuropsychological investigation of schizophrenia. Also, a vast number of brain imaging studies, mostly PET investigations, have employed the CPT as a cognitive challenge and established a relative hypofrontality in schizophrenics compared to controls. The aim of the present investigation was to clarify whether this predescribed hypofrontality could also be verified using functional magnetic resonance imaging (fMRI). 20 healthy volunteers and 14 schizophrenics on stable neuroleptic medication were included. Imaging was performed using the CPT-double-T-version and a clinical 1.5 T MRI-scanner with a single slice technique and a T(2)*-weighted gradient-echo-sequence. The schizophrenics exhibited a decreased activation in the right mesial prefrontal cortex, the right cingulate and the left thalamus compared to controls. These results obtained by fMRI are discussed in relation to published findings using PET.

Adult↗

Myocardial beta-blockade as an alternative to cardioplegic arrest during coronary artery surgery.

The authors' recent experimental work has demonstrated that myocardial protection using continuous coronary perfusion with warm beta-blocker-enriched blood avoids myocardial ischaemia and minimizes myocardial oedema formation, thus completely preserving left ventricle function. The purpose of this clinical study was to compare this alternative technique in terms of structural and functional myocardial protection with the routinely used crystalloid Bretschneider cardioplegia. Sixty coronary artery surgery patients were randomized to receive either crystalloid cardioplegia or continuous coronary perfusion with warm blood enriched with the ultra-short acting beta-blocker esmolol. Cardiac function was evaluated using transoesophageal echocardiography (fractional area of contraction) and cardiac metabolism using arterial-coronary sinus lactate concentration difference (a - csD(LAC)). From left ventricular biopsies, the authors determined myocardial oedema, heat-shock-protein-70, intercellular-adhesion-molecule and actin pattern. Patients with crystalloid cardioplegia received 3.6 +/- 0.8 grafts during 64 +/- 20 min cross-clamp time (beta-blocker: 3.5 +/- 0.9 grafts during 68 +/- 22 min; NS). Following cross-clamp removal crystalloid cardioplegia hearts released significant lactate amounts (a- csD(LAC)) - 1.0 +/- 0.6 versus - 0.1 +/- 0.2 mmol/litre in beta-blocker hearts; P < 0.05). In crystalloid cardioplegia hearts, myocardial water content increased from 82.1 +/- 2.1% pre-cardiopulmonary bypass to 83.2 +/- 1.7% at the end of cardiopulmonary bypass (P < 0.05); in beta-blocker hearts myocardial water content remained unchanged (pre-cardiopulmonary bypass: 82.3 +/- 1.9%; end of cardiopulmonary bypass: 82.4 +/- 1.7%; NS). At the end of cardiopulmonary bypass, left ventricular biopsies of beta-blocker hearts showed less structural damage as determined by heat shock protein-70, intercellular adhesion molecule-I and deranged actin cross-striation pattern as compared with crystalloid cardioplegia hearts (P < 0.05). The post-cardiopulmonary bypass fractional area of contraction was similar in both groups (beta-blocker: 65 +/- 14%; crystalloid cardioplegia: 62 +/- 16%); however, beta-blocker patients required less inotropic stimulation (dopamine: beta-blocker: 2.9 +/- 2.5 versus crystalloid cardioplegia: 5.0 +/- 2.3 microg/kg per min; P < 0.05). The data suggest that continuous coronary perfusion with warm esmolol-enriched blood results in better myocardial protection compared with crystalloid cardioplegia. It is concluded that the concept of beta-blocker-induced cardiac surgical conditions may be a useful alternative for myocardial protection during coronary artery surgery.

Adrenergic beta-Antagonists↗

Increased doxorubicin uptake and toxicity in multicellular tumour spheroids treated with DC electrical fields.

Electrochemotherapy (ECT) is a new approach to the treatment of tumours. In the present study, multicellular prostate tumour spheroids were treated with non-lethal direct current (DC) electrical fields, and uptake and toxicity of doxorubicin were investigated. An electrical field with a field strength of 500 Vm(-1) applied for a duration of 90 s resulted in neither reversible nor irreversible membrane breakdown as revealed by fluid phase uptake studies of the membrane impermeant tracer Lucifer yellow. However, treated spheroids showed an increased uptake of doxorubicin and, consequently, an increased toxicity following electrical field exposure. The electrical field raised intracellular reactive oxygen species (ROS) as revealed using 2',7'-dichlorofluorescein diacetate (H2DCFDA) as an indicator. ROS induced membrane lipid peroxidation since the lipid peroxidation end products malondialdehyde (MDA) and 4-hydroxy-2-(E)-nonenal (4-HNE) were detected after electrical field treatment. Moreover, lipid peroxidation decreased the lipid diffusion coefficient D from 4.2 x 10(-10) cm2 s(-1) to 2.7 x 10(-10) cm2 s(-1) in the control and treated sample, respectively, as revealed by fluorescence recovery after photobleaching (FRAP) experiments. The field effects could be mimicked by incubating spheroids with 100 nM hydrogen peroxide and were inhibited by the radical scavengers dehydroascorbate (DHA) and alpha-tocopherol (vitamin E), indicating that the increased uptake of doxorubicin after electrical field treatment is owing to lipid peroxidation and decreased membrane lipid mobility. Treatment of tumours with low intensity electrical fields may be useful to improve the cytotoxic capacity of anthracyclines.

Antineoplastic Agents↗

Gabapentin leads to remission of somatoform pain disorder with major depression.

Gabapentin, a novel antiepileptic drug, is effective in the treatment of partial seizures with and without secondary generalization. Evidence suggests that it may have mood-stabilizing and possibly antidepressant properties in bipolar depression. We report on a 48-year-old woman who had recurrent major depressive disorder. Following inguinal herniorrhaphy, she developed severe stabbing pain in the lower abdomen and inguinal area that progressed to constant pain in her whole body. She was depressive, hopeless, and had given up her social activities. A diagnosis of major depressive disorder and somatoform pain disorder was made. Antidepressants and carbamazepine were ineffective, and she had attempted suicide. Gabapentin resulted in remission of both the pain and the depressive mood at a dose of 1.800 mg/day.

Acetates↗

Establishment of ionic channels and signalling cascades in the embryonic stem cell-derived primitive endoderm and cardiovascular system.

The first organ system to be established in early embryogenesis is the cardiovascular system which develops upon interaction with hypoblastic cells of the primitive endoderm. Here we focus on recent work on embryoid bodies derived from pluripotent embryonic stem (ES) cells. Ca(2+) oscillations and Ca(2+) signalling pathways during the differentiation of primitive endodermal cell layers are reported. Furthermore, the development-dependent expression of ion channels and the buildup of signalling cascades involved in the modulation of voltage-dependent L-type Ca(2+) channels during early cardiomyogenesis and the formation of functional vascular structures in the process of vasculogenesis and angiogenesis are reviewed. We also report on the use of green fluorescent protein reporter gene expression under the control of cardiac-specific promoters, e.g. the human cardiac alpha-actin promoter, which enables the identification and in vivo characterization of cardiomyocytes at very early stages of cardiomyogenesis.

Animals↗

[Regional implementation of guidelines as a lesson for cancer centers].

43 German Comprehensive Cancer Centers (CCC) are gathered together in a cooperative group (Arbeitsgemeinschaft Deutscher Tumorzentren e.V. = ADT). The main task of these centers is the development of interdisciplinary structures which ensure provision of the optimum facilities of diagnostic procedures, treatment modalities and follow-up management for every patient in all regions of Germany. To realize these efforts, the CCC have to establish expert groups dealing with definite tumor entities and establishing guidelines, which have to be propagated in the respective regions. The experts are responsible for the spreading of relevant information which has to be actualized periodically. The basis of this information system can be the guidelines which are developed together with the German Cancer Society (Deutsche Krebsgesellschaft e.V. = DKG). However, in some cases, the CCC have a longstanding tradition with the elaboration and use of their own guidelines. Yet, these regional guidelines should be in very close congruency with the overlaying national guidelines. Deviations from these general rules have to be explained by the citation of reliable literature from peer reviewed journals. All guidelines must be worked out sticking to the rules of "Evidence Based Medicine" (EBM). An inquiry launched by the ADT revealed different needs in several CCC for further establishment of interdisciplinary expert panels and guidelines.

Cancer Care Facilities↗

Hemispheric differences in frequency dependent dipole orientation of the human auditory evoked field component N100m.

Auditory evoked fields (AEF) of 19 healthy male subjects were recorded bilaterally with a Philips 31 -channel biomagnetometer, using two conditions of stimulation (1000 vs. 5000 Hz tones). The N100m latency was characterized by a single moving dipole for each condition and hemisphere using a boundary element model (BEM) as volume conductor. While the right hemispheric dipole orientations and locations did not change with respect to condition, the left hemispheric dipoles differed significantly between the 1000 and 5000 Hz tones, especially in dipole orientation. The left hemispheric dipoles were orientated on average 10.8 degrees more vertically for the 5000 Hz condition. This result points to interhemispheric differences on the level of sensory processing.

Acoustic Stimulation↗

31Phosphorus magnetic resonance spectroscopy of the dorsolateral prefrontal region in schizophrenics--a study including 50 patients and 36 controls.

BACKGROUND: In a preliminary study we found decreased phosphodiester (PDE)% values and an increased phosphomonoester (PME)/phosphodiester ratio in the dorsolateral prefrontal region (DLPFR) of 13 chronic schizophrenics vs. 14 controls using 31phosphorus magnetic resonance spectroscopy (31P-MRS). Since these results are in contrast to the findings of other groups, we increased our study group to a total of 50 chronic schizophrenics on stable neuroleptic medication and 36 controls to minimize the possibility of a chance result due to small sample size. METHODS: An image-selected in vivo 31P-MRS method on a Philips Gyroscan ACS II scanner working at 1.5 T was used. RESULTS: We could confirm our earlier findings of decreased PDE% levels in schizophrenics. Additionally, we found phosphocreatine (PCr)% and PCr/adenosine triphosphate (ATP) to be increased in the schizophrenics. While no association between PME% and PDE% with neuroleptic medication was found, ATP% correlated positively and PCr/ATP negatively with the chlorpromazine equivalent dose. CONCLUSIONS: The decreased PDE% levels might be characteristic only for chronic, neuroleptic-treated patients. The finding of altered high-energy phosphate levels can be interpreted as an indication of decreased energy-demanding processes in the DLPFR of the investigated patients compared to controls.

Adenosine Triphosphate↗

[Adjuvant chemotherapy in early soft tissue sarcoma and palliative chemotherapy in advanced soft tissue sarcoma in adults].

Adjuvant chemotherapy (chth): The place of postoperative adjuvant chth after complete resection of a primary tumor (R0) is not well established. 13 adjuvant chemotherapy trials with a variety of combinations and most often doxorubicin alone in different regimens were compared to a control group without chemotherapy. Only 2 reports showed a difference in overall survival and 4 some gain in disease-free survival. New studies began with defined inclusion criteria and a control arm without chemotherapy. There are only some risk factors coming into consideration: deep seated tumors with histologic grade 2 and all grade 3 cases. Adjuvant chemotherapy appears justified only within these studies. The potential side effects of adjuvant chemotherapy outside of these trials are detrimental (e.g. 10% cumulative risk of cardiomyopathy after ADM; risk of secondary leukemias) and a benefit is not known. Primary induction chth: Preoperative neoadjuvant chth has to be reserved for studies. They are performed in case of deep seated large primary tumors, not suitable for R0-resection without mutilation. Palliative Chth: In metastatic or locally not curative resectable disease treatment is palliative. The aim of treatment is the relief of existing symptoms or the avoidance of threatening complaints and possibly prolongation of life. The combination of ADM and Ifosfamide (IFO) is commonly used although its superiority to ADM monotherapy is not proven. As second line chemotherapy in case of tumor resistance high dose IFO-monotherapy can be put up for discussion. Myeloablative high-dose-poly-chth with stem cell transplantation remains an experimental approach.

Adult↗

High-energy phosphates in the frontal lobe correlate with Wisconsin Card Sort Test performance in controls, not in schizophrenics: a 31phosphorus magnetic resonance spectroscopic and neuropsychological investigation.

In recent years, a number of 31phosphorus magnetic resonance spectroscopy (P-MRS) studies on the frontal lobe of schizophrenics have been performed, reporting alterations of phospholipids and high-energy phosphates. Deicken et al. (1994b) recently found positive correlations between left frontal phosphomonoester% (PME%) levels and the performance of a specific frontal lobe task, the Wisconsin Card Sorting Test (WCST), in schizophrenics. In the present paper, the correlations between phospholipids and high-energy phosphates in the frontal lobe of 26 schizophrenics and 23 controls measured with a volume-selective P-MRS method were investigated. Overall, we could not find any correlations between WCST results and phospholipid levels, but in controls phosphocreatine% (PCr%) and PCr/adenenosine triphosphate (ATP) ratios were negatively correlated with test performance. Since PCr behaves as a buffer of ATP, in the sense that when ATP is consumed by neuronal activity PCr is catalysed rapidly to ATP, increased PCr% values and, moreover, increased PCr/ATP ratios point to a decreased ATP consumption. Thus, the correlations found between PCr% and PCr/ATP and test performance in controls point to an association between reduced performance in a specific frontal lobe task and decreased energy demanding processes at rest. This association was not found in schizophrenics, possibly due to the influence of neuroleptic medication or the disease process per se.

Adenosine Triphosphate↗