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Biomedical subjects

J Bauer

Publications and source records attributed to J Bauer.

At least 235 records · Page 13Linked to original sources
PubMed1998

New antiepileptic drugs in epileptology.

New antiepileptic drugs have been developed and released for the treatment of chronic focal and secondarily generalized epileptic seizures. The anticonvulsant efficacy of these drugs (vigabatrin, lamotrigine, gabapentin, felbamate, tiagabine, topiramate and oxcarbazepine) does not seem to be superior to that of traditional anticonvulsants. The main advantage of these newly developed drugs is a different spectrum of possible adverse events (i.e. these drugs usually do not induce sedation). Moreover, interactions with traditional anticonvulsants are less common, therefore, comedication with these drugs shows an improved tolerability. The availability of new antiepileptic drugs enables us to establish an individually tailored anticonvulsant strategy for each patient.

Anticonvulsants↗
PubMed1998

An international dermatological image atlas on the WWW: practical use for undergraduate and continuing medical education, patient education and epidemiological research.

We describe the development of an image database DOIA (Dermatological OnlIne Atlas) and present several spin-off projects using images of the atlas, e.g. student education using the atlas including results of an questionnaire evaluating computer-literacy, prerequisites and interests of students for using computers and the World-Wide-Web (WWW), a patient information system and an experiment to collect epidemiological data from patients with dermatological diseases via WWW. The database, available on the WWW at http:@www.derma.med.uni-erlangen.de, contains about 3,000 clinical images covering more than 540 dermatological diagnoses. It is designed for worldwide use; international submissions are encouraged. One aim of the project is to compile an international reference for dermatological images, containing images of high educational quality and also covering conditions on different skin types and rare diagnoses which are not commonly illustrated in ordinary textbooks. All images were originally mapped to the Erlanger Diagnosis Code, which is a proprietary modified ICD-9 key, later also to the UMLS (Unified Medical Language System). In addition, images are described with keys for the location, physical attributes of the location and clinical and histopathological features of the lesion. In order to facilitate the integration of the atlas into other web-based medical resources and to allow easy access to additional information, the Erlanger Diagnosis Code was mapped to the CUIs (unique concept identifiers) of the UMLS Metathesaurus. One purpose of the UMLS is to allow conversion of terms from one controlled medical vocabulary to another, thus, mapping of our diagnosis code to the UMLS CUIs allows simultaneous search for a given diagnosis in a number of other databases and also access to our image database from other databases. Mapping was successful for 619 out of 1383 dermatological diagnosis terms. For images with these diagnoses we are able to provide a hyperlink to other databases available on the Internet, such as MEDLINE, PDQ and OMIM, with automatic retrieval using the preferred vocabulary of the respective database. By grouping all diagnoses into sets with similar morphologies we further integrated a differential diagnosis mode. In order to educate patients via the Internet, a separate patient information system has been developed, using images of the electronic atlas. As an experiment to explore the feasibility of the Internet to gather epidemiological data from patients, users are asked to complete an electronic questionnaire covering signs for atopy. We conclude that an online image atlas has multiple educational, clinical and research applications.

Computer-Assisted Instruction↗
PubMed1998

Convergence and divergence of the signaling pathways for insulin and phosphoinositolglycans.

Phosphoinositolglycan molecules isolated from insulin-sensitive mammalian tissues have been demonstrated in numerous in vitro studies to exert partial insulin-mimetic activity on glucose and lipid metabolism in insulin-sensitive cells. However, their ill-defined structures, heterogeneous nature, and limited availability have prohibited the analysis of the underlying molecular mechanism. Phosphoinositolglycan-peptide (PIG-P) of defined and homogeneous structure prepared in large scale from the core glycan of a glycosyl-phosphatidylinositol-anchored membrane protein from Saccharomyces cerevisiae has recently been shown to stimulate glucose transport as well as a number of glucose-metabolizing enzymes and pathways to up to 90% (at 2 to 10 microns) of the maximal insulin effect in isolated rat adipocytes, cardiomyocytes, and diaphragms (G. Müller et al., 1997, Endocrinology 138: 3459-3476). Consequently, we used this PIG-P for the present study in which we compare its intracellular signaling with that of insulin. The activation of glucose transport by both PIG-P and insulin in isolated rat adipocytes and diaphragms was found to require stimulation of phosphatidylinositol (PI) 3-kinase but to be independent of functional p70S6kinase and mitogen-activated protein kinase. The increase in glycerol-3-phosphate acyltransferase activity in rat adipocytes in response to PIG-P and insulin was dependent on both PI 3-kinase and p70S6kinase. This suggest that the signaling pathways for PIG-P and insulin to glucose transport and metabolism converage at the level of PI 3-kinase. A component of the PIG-P signaling pathway located up-stream of PI 3-kinase was identified by desensitization of isolated rat adipocytes for PIG-P action by combined treatment with trypsin and NaCl under conditions that preserved cell viability and the insulin-mimetic activity of sodium vanadate but completely blunted the insulin response. Incubation of the cells with either trypsin or NaCl alone was ineffective. The desensitized adipocytes were reconstituted for stimulation of lipogenesis by PIG-P by addition of the concentrated trypsin/salt extract. The reconstituted adipocytes exhibited 65-75% of the maximal PIG-P response and similar EC50 values for PIG-P (2 to 5 microns) compared with control cells. A proteinaceous N-ethylmaleimide (NEM)-sensitive component contained in the trypsin/salt extract was demonstrated to bind in a functional manner to the adipocyte plasma membrane of desensitized adipocytes via bipolar interactions. An excess of trypsin/salt extract inhibited PIG-P action in untreated adipocytes in a competitive fashion compatible with a receptor function for PIG-P of this protein. The presence of the putative PIG-P receptor protein in detergent-insoluble complexes prepared from isolated rat adipocytes suggests that caveolae/detergent-insoluble complexes of the plasma membrane may play a role in insulin-mimetic signaling by PIG-P. Furthermore, treatment of isolated rat diaphragms and adipocytes with PIG-P as well as with other agents exerting partially insulin-mimetic activity, such as PI-specific phospholipase C (PLC) and the sulfonylurea glimepiride, triggered tyrosine phosphorylation of the caveolar marker protein caveolin, which was apparently correlated with stimulation of lipogenesis. Strikingly, in adipocytes subjected to combined trypsin/salt treatment, PIG-P, PI-specific PLC, and glimepiride failed completely to provoke insulin-mimetic effects. A working model is presented for a signaling pathway in insulin-sensitive cells used by PIG(-P) molecules which involves GPI structures, the trypsin/salt- and NEM-sensitive receptor protein for PIG-P, and additional proteins located in caveolae/detergent-insoluble complexes.

Adipocytes↗
PubMed1998

Hypoplastic left heart syndrome: "Which is the best operative strategy?".

Therapy for the hypoplastic left heart syndrome (HLHS) is still under debate. We report about our experience in the treatment of this cardiac malformation using heart transplantation and Norwood palliation. From 1988 to 1997 a total number of 30 infants with hypoplastic left heart underwent heart transplantation. Mean age at transplantation was 66 days. Mean waiting time was 53 days. Donor-recipient weight ratio ranged from 0.6 to 3.9. There were 6 early hospital deaths and one late death until now. Causes of death were rejection (3), right heart failure (2), infection (1) and multi system organ failure (1). Overall survival was 77%. Increasing experience improved results substantially. From 1988 to 1993 (n=12) survival rate was 58%, whereas from 1994 to 1997 (n=18) survival rate increased to 88%. Quality of life is excellent in the 23 surviving infants. Only one infant shows severe morbidity (neurological defect). The Norwood procedure has been performed in 18 patients since 1993. Five patients died after the first stage. Up until now 10 infants have undergone the second stage and one infant the third stage procedure. None of them have died. Survival rate is 72% for the whole group. Taking into account that 12 infants died on the waiting list for transplanatation (28%), we have comparable results in terms of the survival rate for transplantation and the Norwood procedure in infants with HLHS since 1994. However quality of life and physical development are far better in infants after transplantation according to our experience. Therefore we prefer, whenever possible heart transplantation in the treatment of hypoplastic left heart syndrome. Certainly not all infants with this malformation can undergo transplantation because of the lack of donor organs. Criteria for the decision regarding the operative strategy in our opinion are function of the right ventricle and tricuspid valve, size of the interaterial communication and parental request.

Cardiac Surgical Procedures↗
PubMed1998

[Comparison of adjuvant chemotherapy in breast carcinoma with a combination of cyclophosphamide, methotrexate, 5-fluorouracil (CMF) and AC (doxorubicin, cyclophosphamide). Initial results of a national cooperative study].

The aim of this multicentric, prospective randomized trial is to evaluate and to compare, effects and toxicities of two chemotherapeutic combinations (AC and CMF) in adjuvant treatment of breast cancer. Both combinations were given in equitoxic doses and number of cycles was only four. There are 106 women treated for breast cancer T1c-3a, N0-1, M0 in the study. After surgery the patients were randomized, 54 for AC combination and 52 for CMF. We evaluate toxicity of this treatment in all patients in the study. Hematological and nonhematological side effects were comparable in both groups except alopecia (in the group AC was 100%). The study is not finished yet. Preliminary analysis does not show any difference between these two groups.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Coarctation of the thoraco-abdominal aorta: operative treatment with a cryopreserved arterial homograft in a seven-year-old boy.

Compared to coarctation in the proximal descending aorta near the insertion of the ligamentum arteriosum, coarctation in the aortic arch, the lower descending or the abdominal aorta is a relatively rare disease. Operative treatment of abdominal coarctation is more complicated if there are concomitant stenoses of visceral or renal arteries. In young patients, surgical procedure and outcome is additionally determined by caliber and compliance mismatch between still growing native vessels and arterial substitute. Our report deals with a seven-year-old male patient, who was first diagnosed as having coarctation of the aorta at five years of age due to distinct bilateral brachial hypertension. The angiogram revealed a narrowing of the aorta, approximately ten centimeters in length, from the lower descending segment down to the proximal abdominal part of the aorta. The origin of the superior mesenteric artery and both renal arteries were not involved in the pathological process. Arterial reconstruction was carried out by anastomosis of cryopreserved arterial homograft with the thoracic aorta and with the abdominal aorta distal to the origin of the renal arteries. The postoperative course was uneventful, duplex sonography revealed no pressure gradient between the thoracic and abdominal aorta and brachial blood pressure was within normal ranges.

Aorta↗
PubMed1998

Potential link between interleukin-6 and arachidonic acid metabolism in Alzheimer's disease.

Prostaglandins (PGs) and cytokines, such as interleukin-1 (IL-1) and interleukin-6 (IL-6), have been implicated in the etiopathology of various inflammatory and degenerative disorders, including Alzheimer's disease (AD). Previously, we detected the presence of IL-6 in cortices of AD patients. On the other hand, non-steroidal antiinflammatory drugs (NSAIDs), potent inhibitors of prostaglandin synthesis, have been shown to be beneficial in the treatment of AD. Until now, it remained unclear whether and how these two observations were functionally connected. Here, we show that PGs are able to induce IL-6 synthesis in a human astrocytoma cell line. PGE1 and PGE2, but not PGD2 and PGF2 alpha, led to a rapid and transient induction of astrocytic IL-6 mRNA, followed by IL-6 protein synthesis. Furthermore, PGE2 potentiated IL-1 beta-induced IL-6 mRNA synthesis. These results suggest a possible link between the release of PGs from activated microglia and the astrocytic synthesis of IL-6, which itself may affect neuronal cells, as hypothesized for Alzheimer's disease. Finally we demonstrate that microglia are a strong source of PGE2 synthesis indicating that these cells may act as the origin of the pathogenic cascade.

Alprostadil↗
PubMed1997

The neuropeptide substance P activates transcription factor NF-kappa B and kappa B-dependent gene expression in human astrocytoma cells.

The neuropeptide substance P is a major mediator of neurogenic inflammation and immunomodulatory activities within the central and peripheral nervous system. In several cell types, substance P induces the expression of proinflammatory cytokines that have been implicated in the pathogenesis of different neuropathologies. Substance P preferentially binds to NK-1, a receptor of the neurokinin family, but how the receptor-elicited signal is translated into inflammatory gene expression is not yet understood. In this work, we describe that in U373 MG astrocytoma cells, nanomolar concentrations of substance P potently triggered activation of NF-kappa B, a transcription factor involved in the control of cytokine expression and apoptosis. Substance P-induced NF-kappa B activation was associated with the increased mRNA expression and secretion of IL-8, an NF-kappa B-controlled target gene. The stimulatory effect of substance P was specific, since an NK-1-selective receptor antagonist completely prevented NF-kappa B activation in response to substance P, but not IL-1 beta. In addition, we show that the activity of substance P required mobilization of intracellular calcium and formation of reactive oxygen intermediates as second messengers. Our results suggest that NF-kappa B may be an important component controlling neurogenic inflammation within the peripheral and central nervous system.

Astrocytoma↗
PubMed1997

The effect of stepwise cerebral hypoperfusion on energy metabolism and amyloid precursor protein (APP) in cerebral cortex and hippocampus in the adult rat.

To study the relationship between cerebral blood flow, energy metabolism, and the formation of amyloid precursor protein (APP), an in vivo animal model was established in which stepwise long-term cerebral hypoperfusion states were induced. Adult rats underwent a stepwise chronic cerebral hypoperfusion by crosswise occlusion of the carotid and vertebral arteries with different periods and severity of hypoperfusion until the final steady-state experiment. Investigations of metabolic compounds were done in hippocampus and parietotemporal cerebral cortex. The analysis of energy-rich phosphates and adenosine was examined by HPLC analysis. Substrate concentrations of pyruvate and lactate were measured spectrophotometrically. The APP holoprotein was investigated by immunblot technique. Long-term cerebral hypoperfusion induced a decrease of energy-rich phosphates in the brain areas studied, whereas the concentration of adenosine and the ATP turnover were increased. Pyruvate decreased, and lactate was increased, pointing to a shift in the cytoplasmatic redox state. More severe changes were found in parietotemporal cerebral cortex in comparison to the hippocampus. After 2-vessel occlusion, the concentration of APP decreased, whereas the APP concentration was significantly increased in rat brain after 4-vessel occlusion. It has been demonstrated for the first time in vivo that the reduction in cerebral energy metabolism alters the formation of APP due to cerebral hypoperfusion.

Amyloid beta-Protein Precursor↗
PubMed1997

Nerve growth factor (NGF) expression in rat microglia is induced by adenosine A2a-receptors.

Microglial response to stimuli is characterized by secretion of both neurotoxic and neurotrophic factors. Various adenosine receptor agonists stimulated the production of nerve growth factor (NGF) in microglia. Using reverse transcription-polymerase chain reaction (RT-PCR)- and ELISA-techniques, we show that the mixed A1- and A2-agonist 5'-(N-ethylcarboxamido)-adenosine (NECA) induces an increase in NGF mRNA expression and NGF protein release. Whereas the A1-specific agonist cyclopentyladenosine (CPA) only minimally affected NGF release, the A2a-specific agonist CGS-21680 triggered the greatest increase in microglial NGF synthesis. Analyzing the selective antagonist (E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine (EXIP), as well as modulators of the cyclic AMP (cAMP) pathway, we identified an adenosine A2a-receptor-sensitive, cAMP-mediated mechanism of microglial NGF synthesis. Our results indicate that A2a-adenosine receptors modulate microglial neurotrophin expression and release.

Adenosine↗
PubMed1997

Expression and regulation of cyclooxygenase-2 in rat microglia.

Increased levels of prostanoids have been implicated in various neuropathological diseases, although little is known about their cellular sources inside the brain. In this study, we analyzed the expression of cyclooxygenase-2 (COX-2), a key enzyme in arachidonic acid metabolism, in rat microglia. COX-2 mRNA and protein as well as prostaglandin E2 formation were almost undetectable in unstimulated microglial cultures but were found to be strongly upregulated in response to lipopolysaccharide. However, in contrast to most peripheral cells, proinflammatory cytokines such as tumor necrosis factor alpha, interleukin-1 beta or interleukin-6 failed to markedly induce COX-2 expression. Similar effects were observed by analyzing transcription nuclear factor-kappa B (NF-kappa B) which was strongly activated in microglia by lipopolysaccharide but not by incubation with cytokines. Moreover, known inhibitors of NF-kappa B activation, such as dexamethasone and the antioxidant pyrrolidine dithiocarbamate, as well as the protein kinase C (PKC) inhibitor Gö6976, strongly reduced lipopolysaccharide-induced COX-2 transcription, indicating the involvement of NF-kappa B and PKC in COX-2 expression. Our results suggest that microglia may represent an important source of prostanoids in the brain, thus reinforcing their prominent role in cerebral inflammatory processes.

Animals↗
PubMed1997

Feasibility, toxicity, and activity of LNH84-derived chemotherapy in the management of aggressive lymphomas.

The results of chemotherapy remain unsatisfactory for many patients with advanced lymphomas. Both standard and more aggressive chemotherapy regimens might have their respective role in the management of theses diseases. We have tested the feasibility and assessed the toxicity and activity of a LNH84-derived chemotherapy for aggressive non-Hodgkin's lymphoma in two general hospitals. Thirty-three untreated patients were included over a period of 4 years. Median age was 39 years, 21 were male. International Working Formulation was F for 2 patients, G for 17, H for 8, I for 1, J for 4, one unclassified. Seventeen patients had B symptoms, 15 stage IV, 8 bulky disease, 21 abnormal LDH, 5 performance status > or =2. The overall response rate was 93%. The single treatment related death resulted from bleomycin acute pneumonitis. Neutropenia WHO grade 4 occurred in all patients, resulting in infections grade 3 in 12 and thrombocytopenia grade 4 in 3. In the induction phase, courses could never be repeated day 14. The dose intensity of the four drugs contained in this phase is thus calculated between 64.5 and 81.5%. At 3 years, overall survival is 80% and event-free survival is 62%. This LNH84-derived regimen is effective. However, the induction phase is toxic and a 3-weekly interval appears more appropriate. Such intensive treatment might benefit patients with very aggressive lymphomas and this should be studied in randomized comparison against standard CHOP.

Adolescent↗
PubMed1997

Cellular electrophoretic mobility data: a first approach to a database.

Cellular electrophoretic mobility values of 288 types of eucaryotic cells were collected from literature published worldwide by a series of authors during the past forty years and arranged in a list. This list contains well-known recent electrophoretic results and also data that cannot be found anymore with modern literature retrieval systems. It will be a valuable help for scientists trying to purify cell populations. In addition, it confirms the observation that most eucaryotic cells have very similar electrophoretic mobilities, ranging from 40% above to 50% below the electrophoretic mobility of human erythrocytes, and thus reinforces the suggestion that electrophoretic mobilities of eucaryotic cells are subjected to strong biological controls.

Animals↗
PubMed1997

Interleukin-6-(IL-6) plasma levels in depression and schizophrenia: comparison between the acute state and after remission.

The concentration of cytokines such as Interleukin-6 (IL-6) has been reported to be elevated in depressed and schizophrenic patients and, in healthy persons, upon stress. Interleukin-6 plasma levels were determined in depressed (n = 12) and schizophrenic (n = 32) patients during the acute state of illness and after remission at approximately 8 weeks after admission and were compared with healthy controls (n = 12). Patients were diagnosed according to DSM-III-R by the Structured Clinical Interview (SCID). Severity of illness was assessed for depression by the Montgomery Asberg Depression Rating Scale (MADRS) and for schizophrenia by the Brief Psychiatric Rating Scale (BPRS). Interleukin-6 plasma concentrations were elevated during the acute state either of depression or of schizophrenia if compared to controls. After remission, IL-6 concentrations in depressed and in schizophrenic patients had decreased and did not differ significantly from controls. We hypothesize that the elevated IL-6 levels during the acute state of depression or schizophrenia may reflect an unspecific stress response.

Acute Disease↗
PubMed1997

[Possibilities for psychotherapy treatment of Alzheimer disease patients in the early stage of the disease].

Psychological changes may precede the neuropsychological symptoms of Alzheimer's disease (AD). In addition, early stages of AD are often accompanied by a depressive disorder. Therefore, we reasoned whether AD patients might profit from psychotherapy. The aim would be to alleviate anxiety, discouragement, and inactivation of patients suffering from the early stages of AD. According to preliminary experience with a small number of treated cases, interpersonal psychotherapy, modified for application in "late-life" (IPT-LL), has been found to be useful for the treatment of AD patients. The case of an AD patient is presented who underwent psychotherapy for two years. Besides describing the special features of such treatment, we address the question of how the next relative (e.g., the spouse) may be included in the therapeutic process.

Adaptation, Psychological↗