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Biomedical subjects

S Koch

Publications and source records attributed to S Koch.

At least 91 records · Page 5Linked to original sources
PubMed1999

Transcranial doppler detection of fat emboli.

BACKGROUND AND PURPOSE: The fat embolism syndrome (FES) is characterized by the simultaneous occurrence of pulmonary and neurological symptoms as well as skin and mucosal petechiae in the setting of long-bone fractures or their surgical repair. Its pathophysiology is poorly understood, and effective treatments are lacking. We present 5 patients with long-bone fractures in whom in vivo microembolism was detected by transcranial Doppler. METHODS: Five patients with long-bone fractures were monitored with transcranial Doppler for microembolic signals (MESs) after trauma. Two patients also had intraoperative monitoring. A TC-2020 instrument equipped with MES detection software was used. Detected signals were saved for subsequent review. Selected signals satisfied criteria defined previously and were categorized as large or small. RESULTS: Cerebral microembolism was detected in all 5 patients and was transient, resolving within 4 days of injury. Intraoperative monitoring revealed an increase in MESs during intramedullary nail insertion. The characteristics of MESs after injury varied among patients, with large signals being more frequent in the only patient with a patent foramen ovale. CONCLUSIONS: Cerebral microembolism after long-bone fractures can be detected in vivo and monitored over time. These findings may have potential diagnostic and therapeutic implications.

Accidents, Traffic↗
PubMed1999

Membrane-based cell culture systems--an alternative to in vivo production of monoclonal antibodies.

A new generation of membrane-based cell culture devices especially designed for small scale production of monoclonal antibodies (mabs) has entered the market in the last few years. In contrast to conventional perfusion hollow fibre bioreactors, these devices contain two functionally different membranes--one ultrafiltration membrane for nutrient supply and one gas-permeable membrane for direct oxygenation of cells. The latest systems of this generation are static culture systems which are of moderate cost and either better than, or equal to, the ascites mice in terms of quality and quantity of produced monoclonal antibodies. We have investigated the advantages of the perfused Tecnomouse bioreactor and the static CELLine culture flasks in comparison to ascites production and conventional roller bottle cultures.

Animal Welfare↗
PubMed1999

The role of the ward manager in creating a conducive clinical learning environment for nursing students.

Ward sisters/managers are without doubt the professional gate keepers of the ward environment yet there are activities in that environment for which they do not seem to take full responsibility, namely that of the clinical learning of nursing students. The aim of this study was to investigate the role of the ward manager in creating a conducive clinical learning environment for nursing students. An explorative descriptive research method was employed. Findings reveal that the ward managers are generally satisfied with the way in which they handle the important role they play in facilitating teaching and learning for nursing students. They feel strongly, however, that the nursing students themselves need to be active in the learning process. While acknowledging the efforts of the ward managers in creating and maintaining the learning environment, nursing students were dissatisfied about several aspects that appeared to be lacking in the clinical environment, such as good interpersonal relations, support, exposure to practice administrative skills (for example, problem-solving and decision-making) and lack of feedback about their performance. There appears to be a need to develop more effective support structures within the learning environment so that nursing students can obtain sufficient exposure to learning opportunities.

Attitude of Health Personnel↗
PubMed1998

Biodiversity assessment and conservation strategies

The efficient representation of all species in conservation planning is problematic. Often, species distribution is assessed by dividing the land into a grid; complementary sets of grids, in which each taxon is represented at least once, are then sought. To determine if this approach provides useful surrogate information, species and higher taxon data for South African plants and animals were analyzed. Complementary species sets did not coincide and overlapped little with higher taxon sets. Survey extent and taxonomic knowledge did not affect this overlap. Thus, the assumptions of surrogacy, on which so much conservation planning is based, are not supported.

Journal Article↗
PubMed1998

Highly-efficient gene transfer with retroviral vectors into human T lymphocytes on fibronectin.

Genetically modified lymphocytes have been successfully used for correction of ADA deficiency in children and in controlling graft-versus-host disease (GvHD) after allogeneic bone marrow transplantation. Low transduction efficiencies are, however, limiting for gene therapeutic strategies based on lymphocytes. In this study we compared protocols for highly efficient gene transfer into human T cells using retroviral vector-containing supernatant. We showed that infection of both human primary T cells and CD4+ Jurkat cells is most efficient on the matrix component fibronectin. Transduction was carried out with a retroviral vector encoding both the human intracytoplasmatically truncated low-affinity nerve growth factor receptor (deltaLNGFR) as a gene transfer marker and the Herpes simplex virus thymidine kinase for negative selection. Based on LNGFR expression genetically modified cells were enriched to near purity by magnetic cell sorting (MACS). Enriched cells could be shown to be highly sensitive to ganciclovir.

Anti-Allergic Agents↗
PubMed1998

Intraspinal injection of adenosine agonists protect against L-NAME induced neuronal loss in the rat.

Intraspinal injection of the nonspecific inhibitor of nitric oxide synthase N-nitro-L-arginine methyl ester (L-NAME) results in a dose-dependent loss of neurons in the rat spinal cord. This effect is thought to result from a reduction in basal levels of nitric oxide (NO), thereby producing an ischemic reaction secondary to vasoconstriction and reduced spinal cord blood flow (SCBF). An important component of this ischemic reaction is the release of excitatory amino acids and the initiation of an excitotoxic cascade. In the present study, microinjections of adenosine A1 and A2 receptor agonists were made in the spinal cord to evaluate the neuroprotective effects of these drugs against neuronal loss produced by L-NAME. Animals were divided into six groups based on the composition of injected solutions: (a) L-NAME; (b) L-NAME + N6-cyclopentyladenosine (CPA, A1 agonist); (c) L-NAME + 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA, A2 agonist); (d) L-NAME + CPA + CPCA; (e) N-methyl D-aspartate (NMDA); and (f) NMDA + CPA. Injections of L-NAME or NMDA produced a unilateral loss of spinal neurons, a local inflammatory response, and darkly stained pyknotic nuclei surrounding the area of neuronal loss. CPA and CPCA significantly reduced the area of L-NAME-induced neuronal loss, and a synergistic effect was observed when ineffective doses of these agonists were co-injected with L-NAME. The excitotoxic effects of NMDA were not affected by CPA. The results have shown that A1 and A2 receptor agonists provide significant neuroprotection against L-NAME induced neuronal loss, presumably by inhibiting ischemia induced release of excitatory amino acids (A1 agonist), or by restoring SCBF secondary to vasodilation (A2 agonist). It is suggested by these results that the intraspinal injection of L-NAME is an effective model to study the pathological consequences of vasoconstriction, reduced SCBF, and ischemia secondary to decreased NO production in the rat spinal cord. Finally, the results provide support for the continued investigation of specific adenosine agonists as therapeutic agents directed against the ischemic and excitotoxic components of spinal injury.

Adenosine↗
PubMed1998

New concept of an integrated IT&T-based dental workstation for quality assurance in oral health care.

During the last five years, quality development has become a most important issue in oral health care. In every day practice, quality development meets, however, a considerable number of objective obstacles, mainly due to the lack of direct access to the information necessary in a specific clinical work situation and due to the absence of knowledge on own performance in relation to quality goals. The EU-TAP project ORQUEST has identified different clinical work situations and built up an integrated IT&T-platform composed of different software modules and hardware components for each clinical work situation in order to allow for adequate IT&T-support in specific clinical situations.

Cognition↗
PubMed1998

Tyrosinase, melan-A, and KBA62 as markers for the immunohistochemical identification of metastatic amelanotic melanomas on paraffin sections.

The authors retrospectively tested the potential value of paraffin-reactive monoclonal antibodies (A103 against melan-A, T311 against tyrosinase) and antibody KBA62 as immunohistochemical markers for amelanotic metastatic melanomas. The study cases included 72 amelanotic metastases of known cutaneous melanomas, 59 poorly differentiated carcinomas, 73 sarcomas of varying histogenesis, 4 Leydig cell tumors, 10 high-grade lymphomas, and 6 plasmoblastic/anaplastic myelomas. The results were compared with immunostainings for S-100 protein and HMB-45. HMB-45, antimelan-A, and antityrosinase showed almost identical staining results, with a sensitivity of 0.85 for HMB-45 and of 0.86 for both antimelan-A and for antityrosinase. HMB-45 and antityrosinase both had a specificity of 1.00; the specificity of antimelan-A was 0.95 as a result of a positive reaction in three of three adrenocortical carcinomas and four of four Leydig cell tumors. KBA62 stainings resulted in a sensitivity of 0.86 for melanomas. A positive immunoreactivity of KBA62 alone had a specificity of only 0.83, but in conjunction with anti-S-100 protein (sensitivity, 1.00; specificity, 0.87) and anticytokeratin 8/18/19 (CK), a KBA62+/S-100+/CK- immunophenotype identified all except one of the melanoma cases that were negative for the three melanocyte-specific markers with a specificity of 0.99. In conclusion, we found comparable immunohistochemical sensitivities of HMB-45, antityrosinase, and antimelan-A for a highly specific identification of approximately 85% of amelanotic metastatic melanomas on paraffin sections. Melanomas that were negative for all of these specific markers might be sensitively and specifically detected with anti-S-100 protein and KBA62.

Antibodies, Monoclonal↗
PubMed1997

Selective immunoaffinity-based enrichment of CD34+ cells transduced with retroviral vectors containing an intracytoplasmatically truncated version of the human low-affinity nerve growth factor receptor (deltaLNGFR) gene.

Human hematopoietic stem cells remain one of the most promising target cells for gene therapeutic approaches to treat malignant and nonmalignant diseases. To rapidly characterize transduced cells and to isolate these from residual nontransduced, but biologically equivalent, cells, we have used a Moloney murine leukemia virus (Mo-MuLV)-based retroviral vector containing the intracytoplasmatically truncated human low-affinity nerve growth factor receptor (deltaLNGFR) cDNA as a marker gene. Supernatant transduction of CD34+ cells (mean purity 97%) in fibronectin-coated tissue culture flasks resulted in 5.5-45% (mean 26%) transduced cells expressing deltaLNGFR (LNGFR+ cells). After transduction, more than 65% of the transduced cells remained CD34+. Compared with control (mock- and nontransduced) CD34+ cells, transduction did not decrease the cloning efficiency of CD34+ cells. Immunomagnetic selection of the transduced cells with a monoclonal anti-LNGFR antibody resulted in >90% LNGFR+ cells. Further phenotypic characterization of these highly enriched LNGFR+ cells indicated that the majority co-expressed the CD34 and CD38 antigens. These results show that transduced cells expressing an ectopic cell-surface protein can be rapidly and conveniently quantitated and characterized by fluorescence-activated cell sorting (FACS) analysis and fast and efficiently enriched by immunoadhesion using magnetic beads. The use of cell-surface reporters should facilitate optimization of methods of gene transfer into more primitive hematopoietic progenitors.

Animals↗
PubMed1997

Interactions between cocaine and (-)-DS 121: studies with 2-deoxyglucose autoradiography and microdialysis in the rat brain.

(-)-DS 121 [S-(-)-3-(3-cyanophenyl)-N-n-propyl piperidine], a dopamine autoreceptor preferring antagonist, has been shown to stimulate locomotor activity and induce conditioned place preference. However, the drug fails to facilitate intracranial self-stimulation or substitute for cocaine in cueing experiments, and it blocks cocaine self-administration. In the present study using 2-deoxyglucose autoradiography, (-)-DS 121 (at 50 but not 15 mg/kg i.p.) significantly and selectively increased local cerebral glucose utilization in the olfactory cortex, medial and lateral septum, hippocampal areas, substantia nigra pars reticulata, caudate, and mammillary body. Local cerebral glucose utilization was depressed in caudal areas of the cortex. Interestingly, however, both doses of (-)-DS 121 blocked the increases in local cerebral glucose utilization produced by 5 mg/kg i.v. cocaine. The present study also evaluated the effects of (-)-DS 121 of extracellular striatal dopamine levels using microdialysis in freely moving rats. By itself, 15 mg/kg of (-)-DS 121 increased extracellular striatal dopamine levels to approximately 300% of controls. Cocaine (5 mg/kg i.v.) produced a 370% increase in striatal dopamine levels. When rats were pretreated with (-)-DS 121, a subsequent dose of cocaine augmented the increase in extracellular striatal dopamine to 870% of controls. The results support the contention that (-)-DS 121 possesses weak cocaine-mimetic effects and that its antagonism of cocaine's subjective effects are due to interactions with dopamine at postsynaptic sites. It is hypothesized that, like other preferential autoreceptor antagonists, (-)-DS 121 may be useful as a pharmacotherapy in drug addiction.

Animals↗
PubMed1997

Effects of piracetam on membrane fluidity in the aged mouse, rat, and human brain.

In vitro preincubation of brain membranes of aged mice with piracetam (0.1-1.0 mmol/L) enhanced membrane fluidity, as indicated by decreased anisotropy of the membrane-bound fluorescence probe 1,6-diphenyl-1,3,5-hexatriene (DPH). Piracetam had similar in vitro effects on brain membranes of aged rats and humans, but it did not alter brain membrane fluidity in young mice. Chronic treatment of young and aged rats with piracetam (300 mg/kg once daily) significantly increased membrane fluidity in some brain regions of the aged animals, but had no measurable effect on membrane fluidity in the young rats. The same treatment significantly improved active avoidance learning in the aged rats only. It is suggested that some of the pharmacological properties of piracetam can be explained by its effects on membrane fluidity.

Aged↗
PubMed1997

Tumor necrosis factor alpha (TNF alpha) is cardiodepressant in pathophysiologically relevant concentrations without inducing inducible nitric oxide-(NO)-synthase (iNOS) or triggering serious cytotoxicity.

Cardiac hypertrophy and heart failure are frequently accompanied by elevated plasma levels of tumor necrosis factor alpha (TNF alpha), the pathogenetic relevance of this finding being a matter of debate. In human acute septic cardiomyopathy, on the other hand, the negative inotropic impact of TNF alpha on the heart is well documented and frequently ascribed to the induction of inducible nitric oxide (NO) synthase (iNOS) and an enhanced production of NO in the heart. Yet the present study presents evidence that in cardiomyocytes TNF alpha in non-toxic concentrations specifically depresses contractile performance independent of NO. In spontaneously beating neonatal rat cardiomyocytes, TNF alpha in a low, pathophysiologically relevant concentration (10 U/ml, 1-3 days) does not alter basal pulsation amplitude, but blocks alpha- and beta-adrenoceptor-stimulated increase in contractility and beating irregularity and impairs the impact of high extracellular calcium on contractile performance. However, this low TNF alpha-concentration does not suffice to induce iNOS - documented by reverse transcriptase polymerase chain reaction - or enhance nitrite concentrations in the cell culture supernatants as a measure of cellular NO production, neither in the presence nor absence of dexamethasone (0.1 micro M). Only in high concentration - the specific proinflammatory action being documented by an enhanced release of interleukin-6 from cardiomyocytes - TNF alpha (1000 U/mol; 6, 24 h) weakly induces the mRNA for iNOS, with a consecutive moderate rise in cellular nitrite production. TNF alpha-incubation (10-1000 U/ml) does not alter the morphological appearance of the cells displayed by phase contrast microscopy or evoke gross cytotoxicity.

Animals↗
PubMed1997

MDMA induced dopamine release in vivo: role of endogenous serotonin.

Acting as a substrate at the serotonin (5-HT) transporter, (+)-MDMA (3,4-methylenedioxymethamphetamine), is a potent releaser of 5-HT and causes toxicity to 5-HT neurons after repeated exposure. (+)-MDMA also releases dopamine (DA), although with less potency. Since we have shown previously that the intrastriatal application of 5-HT facilities DA release, it was hypothesized that increased release of striatal 5-HT after MDMA may influence extracellular levels of DA. Using microdialysis in vivo, we found that (+)-MDMA (4.7 mumol/kg, i.v.) administration increased extracellular striatal DA levels to 501% of control (p < 0.01, n = 12). However, in the presence of fluoxetine (14.4 mumol/kg, s.c.), which prevents (+)-MDMA effects on 5-HT release, the (+)-MDMA-induced increase in DA was significantly less (to 375% of control, p < 0.05, vs. no fluoxetine, n = 8). In vitro studies with striatal slices, to test drug selectivity, showed that (+)-MDMA (0.3-3 microM) increased extracellular levels of both DA and 5-HT in a dose-dependent manner. Fluoxetine (3 microM) completely blocked the effects of (+)-MDMA on 5-HT release, but did not alter (+)-MDMA-induced DA release in vitro. The selective DA transport inhibitor GBR-12909 (1 microM), blocked (+)-MDMA's effect on DA release. It is concluded that 5-HT release after (+)-MDMA treatment partially contributes to (+)-MDMA's effect on DA release in vivo.

Animals↗
PubMed1997

[Anatomical comment: Hohmann retractor. A source of danger to the sciatic nerve.].

In referring to the article by Stühmer the authors describe the topographic relationship between the sciatic nerve and an inserted normal Hohmann retractor or a specially designed retractor by Stühmer. By simulating the surgical circumstances the following observations are made:In lateral position and with external rotation of the hip the sciatic nerve is found directly posterior to the major trochanter. When inserting the Hohmann retractor its point slips between the trochanter and the sciatic nerve. The nerve lies directly on the retractor or can be injured by inserting it. Contrary to this the Stühmer retractor avoids pressure on or skewing of the nerve.

English Abstract↗
PubMed1997

Cartilage and bone morphology in osteochondritis dissecans.

Osteochondritis dissecans (OD) is a syndrome that can be characterized as a non-infectious disturbance of enchondral ossification or as a post-traumatic event. OD occurs in the joint cartilage and physis of long bones, as well as in the talus or metacarpal head especially of young athletes. The medial femoral condyle is the most commonly affected site. The causes of osteochondritis dissecans are poorly understood. Thirty human osteochondral cylinders from patients (aged 16-44 years) with osteochondritis dissecans of the medial femoral condyle (grades IV and V according to Rodegerdts and Gleissner) were harvested intraoperatively from osteochondritic areas as part of a cartilage-bone transplantation. Light microscopy, electron microscopy, and immunohistochemistry using poly- and monoclonal antibodies against collagens and glycosaminoglycans revealed differences between osteochondrotic and normal cartilage. Staining with toluidine blue at pH 1 shows a decrease in acidic glycosaminoglycans in OD. Modified pentachrome staining showed a thinned subchondral growth plate compared to normal osteochondral samples. Borders to the healthy tissue are clearly visible micro- and macroscopically. Scanning electron microscopy revealed structural differences in the subchondral area. Immunohistochemistry found a general decrease in glycosaminoglycan content and a change in composition. Only faint staining for chondroitin and keratan sulfates was observed in osteochondritic cartilage, whereas increased staining was shown for keratan sulfate in bone.

Adolescent↗