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Biomedical subjects

G Bauer

Publications and source records attributed to G Bauer.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Fatal methadone poisoning of a child].

The substance methadone is used for substitution therapy since the 1960s in the U.S. Mainly because of the endemic spread of HIV-1 infections among intravenous drug abusers methadone was made legally available through medical prescription in Austria in 1987. Legal authorities today also allow the patient to take home the necessary daily consumption for weekends or public holidays. The drug is distributed as a watery solution in tiny bottles, which are fitted with an ordinary screw cap. This kind of distribution may, however, have fatal consequences. This is demonstrated in the following case of accidental poisoning of an infant: A two-year-old girl whose parents were both participating in the substitution scheme was found dead in her bed in Vienna in 1997. Forensic autopsy revealed a methadone concentration in the liver tissue of 640 ng/g. The criminal investigation determined that the girl had opened a bottle of methadone solution and subsequently had taken the drug. Considering the circumstances of this accident, from the medical point of view safety devices for the screw caps of the methadone bottles should be required by law, in order to avoid future accidental poisoning.

Accidents, Home↗
PubMed2000

Suicide of a body packer.

The smuggling of illicit drugs by means of body packing has become a common problem at European airports. Europe is considered to be the fastest growing market for cocaine worldwide, and the air route is the most frequently used method of trafficking cocaine. Smuggling illicit drugs by use of body packing is considered to be a high toxicological hazard because of the risk of leakage or a package bursting. We report about the first case of suicide of a body packer by re-ingesting the content of excreted cocaine packages. The consequence of this case is that the death scene investigation and autopsy assessments in case of a body packer's death should always consider the possibility of re-ingested packages. Detention personnel should be instructed by forensic and criminalistic experts to take preventive measures.

Adult↗
PubMed2000

Intrakines--evidence for a trans-cellular mechanism of action.

Human CXCR4 is the receptor for the CXC chemokine SDF-1alpha and also acts as a coreceptor for T lymphotropic HIV-1 strains. Blocking the surface expression of this receptor via an intrakine approach has recently been shown to efficiently prevent HIV-1 infection of T cells. The CXC-chemokine gene is fused to an endoplasmic reticulum retention signal (KDEL) that retains the newly synthesized chemokine and its receptor within the cell, where both are subsequently degraded. We constructed MoMuLV-based vectors containing the SDF-KDEL construct driven by the "MND" long terminal repeat, using eGFP as a marker gene (MND-SDF-KDEL-IRES-eGFP) and a control vector (MND-X-IRES-eGFP). CEM human T lymphoblastic leukemia cells were transduced with the intrakine vector or the control vector. We detected a marked downregulation of CXCR4 expression in the cells transduced with the intrakine vectors as opposed to the cells transduced with the control vector. However, the eGFP-negative fraction of the cells transduced with the intrakine vector displayed the same CXCR4 downregulation as the eGFP-positive fraction, suggesting an effect in trans. The possibility of this being due to eGFP being silenced while SDF-KDEL was still expressed was excluded by Southern and Northern blot analyses. Upon cultivating the control cells with supernatant of the cells transduced with the intrakine vector, we observed a downregulation of CXCR4 expression on the control cells. Experiments using rhSDF-1alpha showed downregulation by the supernatant to be comparable to that achieved by the exogenous addition of 30 ng/ml SDF-1alpha. To assess the bioactivity of the secreted substance in the supernatant, a chemotaxis assay was performed. The transmigration observed was, once again, within the range of that achieved by the addition of 30 ng/ml SDF-1alpha. We conclude that the intrakine SDF-KDEL, apart from acting within the cell, is also in part secreted and causes the downregulation of the receptor by acting like a secreted chemokine.

Blotting, Northern↗
PubMed2000

Diet in residents of East and West Germany in 1991-1992 as ascertained by a retrospective food frequency questionnaire.

In this study, we compared dietary habits of residents in East (N = 76) and West Germany (N = 266) using results obtained in 1992-1993 from a retrospective semi-quantitative food frequency questionnaire referring to 1991-1992. Nutrient intakes were calculated based on the German Federal Food Code. Univariate and multivariate logistic regression was used to determine whether dietary intakes varied according to residence in East and West Germany. At the food level, East German subjects reported a higher consumption of bread, spreadable fat, and sausage, whereas West German participants reported a higher intake of fruit, vegetables, and pasta and rice. At the macronutrient level, energy intake did not differ significantly between groups, nor did the percent contribution of protein, carbohydrate, fat, and alcohol to total energy intake. East German participants had a lower total water and fibre intake, the latter significant only after adjustment for confounders. At the micro-nutrient level, East German participants had a higher intake of cobalamin, retinol and retinol-equivalents (but not of beta-carotene). There were no differences in the intake of vitamins C, D, and E between groups. Less salt and more potassium, calcium, magnesium and zinc were consumed by West than by East German subjects. Overall, both groups showed disadvantageous dietary patterns. The results are discussed in the context of an overview of other dietary surveys performed in the two parts of Germany before and after reunification. In general our results are consistent with other observations showing that dietary habits in East Germany rapidly approached those in West Germany after reunification, although some residual differences seemed to persist.

Adult↗
PubMed2000

Regulation of proliferation and apoptosis in sporadic and hereditary medullary thyroid carcinomas and their putative precursor lesions.

C-cell hyperplasia (CCH) and medullary thyroid carcinoma (MTC) in patients affected by germline mutations of the RET oncogene represent an exceptional opportunity to study the regulation of proliferation and apoptosis during tumour initiation and progression. In 56 specimens [CCH, n=1; MTC with CCH, n=26; MTC, n=20; lymph-node metastasis (LNM), n=9] from 46 patients [multiple endocrine neoplasia type 2a (MEN2a), n=24; MEN2b, n=2; familiar MTC (FMTC), n=4; sporadic MTC, n-16] and 3 cases of non-neoplastic CCH, proliferation activity (MIB1), the rate of apoptosis [dUTP nick end labelling (TUNEL)] and expression of p53, bcl-2, bcl-x and bax were investigated and compared with clinical data. In MEN-associated CCH and small MTC, bcl-2 was strongly expressed, bcl-x was moderately expressed and bax was only weakly expressed. Advanced tumours and LNM did show a more heterogeneous bcl-2 staining accompanied by an increased bax expression and accelerated proliferation. The rate of apoptosis was extremely low in all investigated tumours. P53 was detectable in three patients with rapidly growing and extensively metastasising MTC. No somatic p53 mutations were found. Hereditary MTC with germline RET mutations at codon 918 (MEN2b) and codon 634 revealed a bias towards a higher proliferation activity at a younger age and are more frequently accompanied by LNM. CCH and MTC are characterised with a preponderance of bcl-2 as a factor blocking the programmed cell death. While MTC, in general, is a slowly growing tumour, a minority of tumours do progress rapidly with high proliferation. The factors leading to an accelerated tumour progression do not seem to take their effect via the regulation of apoptosis. Certain alterations of RET are supposed to have a direct or indirect implication on proliferation and, because of this, an effect on the clinical course.

Adolescent↗
PubMed2000

Metastability of Si1-yCy epilayers under 2 MeV alpha-particle irradiation

In this work we present some recent results concerning the alpha-particles irradiation of Si1-yCy alloy epitaxially grown on silicon. The study of the damage process is interesting because of the extensive use of backscattering technique as a tool of characterisation of this kind of materials and because of the possibility of adding information about the transformations that this metastable material undergoes. We point out that the irradiation damage process causes a change in the material structure different from that due to the thermal treatments. The irradiation damage occurs at a rate much higher than in Si, however it involves only a silicon atom fraction that appears to be proportional to the substitutional carbon content.

Journal Article↗
PubMed2000

Change of sternal perfusion following preparation of the internal thoracic artery--a scintigraphical study.

BACKGROUND: Today the internal thoracic artery (ITA) is the bypass graft of choice due to its superior long-term patency rate. It was the aim of this present prospective study to investigate possible perfusion disturbances and consecutive impaired wound healing induced by the ITA preparation. The sternal perfusion was assessed by bone scintigraphy. METHODS: Forty-four patients were included in the study. There were three groups: group I (control, no ITA preparation; n = 12); group II (preparation of the left ITA; n = 21); group III (preparation of both ITAs; n = 11). In all patients a median sternotomy was performed. A bone scintigraphy was performed 4 days before and 12 days after the bypass procedure. Scintigraphical pictures of all patients were assessed visually (one specialized investigator) and the impulse rate was counted by the aid of a computer program. RESULTS: Results of both evaluation methods showed congruently that neither the use of the left nor of both ITAs causes a statistically significant impairment of sternal perfusion. The percentage of postoperative increase of the rate of impulses was in group I: total sternum 55%; right side 56%; left side 55%. The respective numbers for group II were 58, 63 and 53%, and for group III 54, 52 and 56%. Surprisingly, perfusion scans in group II revealed an increase in the right sternal half after left ITA preparation. This may be due to the additional blood flow demand of collaterals branching between the right ITA and contralateral intercostal arteries representing a compensatory mechanism of the loss of the left ITA. During the observed postoperative time frame (mean 15 days) no healing disturbance of the sternal wound occurred in any patient. CONCLUSION: According to the present data the use of one or both ITAs does not cause an increase of healing disturbances, consecutive to a postoperatively decreased sternal blood perfusion.

Adult↗
PubMed2000

Quality of heroin and heroin-related deaths from 1987 to 1995 in Vienna, Austria.

AIMS: To investigate the quality of heroin seized in Vienna between 1987 and 1995 and to examine whether there was a relationship between the quality of heroin and the rate of drug-related deaths. DESIGN: Reports of heroin seizure analysis and post-mortem reports of heroin-related deaths in Vienna from 1987 to 1995 were analysed. RESULTS: There were 386 seizures of heroin comprising a total weight of 25 640.12 g heroin. All the seizures were in the base form. All seizures also contained a diluent, mainly lactose. Additionally, in 95 seizures caffeine, in four seizures paracetamol and in three seizures metaqualon were detected. Of a total of 764 drug-related deaths 506 cases were classified as heroin-related deaths. In 336 cases other central nervous system-depressant drugs and/or alcohol could be detected in the blood in addition to morphine (polydrug heroin-related deaths). There was evidence of a trend towards greater polydrug involvement during the study period. The age of victims of polydrug heroin-related deaths remained unchanged over time while the age of victims of pure heroin-related deaths decreased significantly. The morphine concentration in the medulla oblongata in heroin-related deaths decreased significantly. Finally, there was no statistically significant relationship between the rate of heroin-related deaths per year and the diacetylmorphine concentration of heroin seizures in that year. CONCLUSION: The results did not substantiate the widely held belief that increases in heroin-related deaths could be explained by an increase in the quality of heroin.

Adolescent↗
PubMed2000

Gabapentin-induced mood changes with hypomanic features in adults.

We report two adults who received gabapentin (GBP) and subsequently developed behavioural side effects. Indications for GBP treatment were newly diagnosed epilepsy in one and painful paraesthesiae in the other. Both had no past history of psychiatric or behavioural disorder. Abnormal behaviour consisted of elevated mood, euphoria, and increased energy in both patients, and pressure of speech and decreased need for sleep in one of them. These symptoms were transient and fully reversible. One patient had to discontinue GBP. Behavioural changes were not related to seizure activity. They should be recognized as a possible side effect of GBP treatment in adults.

Acetates↗
PubMed2000

Gene therapy for pediatric AIDS.

Gene therapy is an experimental treatment modality under investigation for applications to HIV-1 infection. We have developed retroviral vectors carrying anti-HIV-1 genes, demonstrated that these genes cause significant suppression of HIV-1 replication in cultures of primary hematopoietic cells, and performed a clinical trial in pediatric AIDS patients. Four HIV-1-infected children and adolescents underwent bone marrow harvest from which CD34+ cells were isolated and transduced by a retroviral vector carrying an RRE decoy gene. The cells were re-infused into the subjects, without complications, showing that gene transfer in pediatric AIDS patients in safe and feasible. However, gene-containing leukocytes in the peripheral blood were seen only at a low level and only in the first months following cell infusion. To attain some degree of efficacy, it will be necessary to achieve a higher level of gene transfer and to obtain sustained gene expression. We are currently developing new gene transfer methods and vectors designed to improve the results in future trials. If it becomes possible to reach the ideal goal of producing high percentages of T lymphocytes and monocytic cells that are resistant to HIV-1 infection, gene therapy could serve as a complement to antiretroviral drug therapy and help to sustain immunologic function.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Transformed target cell-derived superoxide anions drive apoptosis induction by myeloperoxidase.

Myeloperoxidase induces apoptosis in src- or raxs-transformed fibroblasts, but not in parental nontransformed fibroblasts. This selectivity seems to be based on superoxide anion production by transformed cells, a recently described characteristic feature of transformed cells. Myeloperoxidase-mediated apoptosis induction is inhibited by SOD, catalase, 4-aminobenzoyl hydrazide, taurine and DMSO. This pattern of inhibition allows us to conclude that transformed cell derived superoxide anions dismutate to hydrogen peroxide, which fosters HOCl formation by myeloperoxidase. Hydrogen peroxide formation thereby is the rate-limiting step and depends on the cell density. In a second step, HOCl interacts with superoxide anions to yield the highly reactive apoptosis inducing hydroxyl radical. This conclusion was verified through selective apoptosis induction in transformed cells by direct addition of HOCl, which was also inhibited by SOD and DMSO. Our findings demonstrate a specific interplay between target cell derived superoxide anions and MPO during selective apoptosis induction.

Apoptosis↗
PubMed2000

Oncogenic transformation increases the sensitivity for apoptosis induction by inhibitors of macromolecular synthesis.

Inhibition of RNA or protein synthesis causes apoptosis in fibroblasts. This points to the constitutive expression of a long-lived apoptosis machinery which is controlled by shortlived negative regulatory proteins, termed endogenous survival factors. The length of time between addition of the inhibitor of macromolecular synthesis and the onset of apoptosis can be used as an estimation of the effective survival factor concentration. Transformation of rat fibroblasts by a constitutively expressed src oncogene or an inducible ras oncogene increases the sensitivity for apoptosis induction by inhibitors of macromolecular synthesis, indicating that their endogenous survival factor pool has been decreased.

Animals↗
PubMed2000

Reversible and oxidative inactivation of endogenous survival factors after removal of exogenous survival factors.

Serum contains exogenous survival factors for fibroblasts. Removal of these exogenous factors causes inactivation of endogenous survival factors, subsequent release of a constitutively expressed apoptosis machinery from negative control and apoptosis. Inactivation of endogenous survival factors after serum withdrawal is mediated by reactive oxygen species and can be rapidly reversed through re-addition of serum. Oxidative inactivation of endogenous survival factors after depletion of exogenous survival factors as well as the process of reversion to the active state do not require protein synthesis, indicating the existence of a constitutively expressed regulatory system that controls the interaction of exogenous and endogenous survival factors.

Animals↗
PubMed1999

A clinical trial of retroviral-mediated transfer of a rev-responsive element decoy gene into CD34(+) cells from the bone marrow of human immunodeficiency virus-1-infected children.

Genetic modification of hematopoietic stem cells with genes that inhibit replication of human immunodeficiency virus-1 (HIV-1) could lead to development of T lymphocytes and monocytic cells resistant to HIV-1 infection after transplantation. We performed a clinical trial to evaluate the safety and feasibility of this procedure, using bone marrow from four HIV-1-infected pediatric subjects (ages 8 to 17 years). We obtained bone marrow, isolated CD34(+) cells, performed in vitro transduction with a retroviral vector carrying a rev-responsive element (RRE) decoy gene, and reinfused the cells into these subjects with no evidence of adverse effects. The levels of gene-containing leukocytes in peripheral blood samples in the 1 year after gene transfer/cell infusion have been extremely low. These observations support the potential of performing gene therapy for HIV-1 using hematopoietic cells, but emphasize the need for improved gene transfer techniques.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Hypertonic saline induces prostacyclin production via extracellular signal-regulated kinase (ERK) activation.

BACKGROUND: Hypertonic saline (HTS) resuscitation exerts protective effects in reperfusion injury including a decrease in pulmonary vascular resistance and an increase in microvascular perfusion and cerebral blood flow; however, the mediators of these effects are unknown. Prostacyclin (PGI2) is a paracrine mediator with two main effects, vasodilation and inhibition of platelet aggregation. We hypothesized that HTS may induce PGI2 production by endothelial cells. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with varying concentrations of NaCl. After 12 h of incubation, the supernatant was assayed for 6-keto-prostaglandin F1, a stable metabolite of PGI2, by ELISA. Phospho-specific ERK-1 and ERK-2 mitogen-activated protein kinase (MAPK) antibody, which recognizes only activated ERK, was used to determine ERK activation status by Western blotting. RESULTS: Addition of 20-100 mM NaCl or endotoxin [lipopolysaccharide (LPS)] induced PGI2 production by HUVECs. HTS and LPS induced ERK-1 and ERK-2 activation. PGI2 production was inhibited when the HUVECs were pretreated with PD 98059, a specific inhibitor of ERK phosphorylation. CONCLUSION: These data suggest that HTS induces PGI2 production in HUVECs. In addition, HTS and LPS induce activation of ERK which is required for PGI2 production. HTS resuscitation may improve microvascular circulation and decrease reperfusion injury via induction of PGI2 production by endothelial cells.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

Evaluation of a putative major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q14.

Juvenile myoclonic epilepsy (JME) is a genetically determined common subtype of idiopathic generalized epilepsy (IGE). Significant evidence for linkage has been reported for a susceptibility locus for JME in the chromosomal region 15q14 that harbors the gene encoding the alpha7 subunit of the neuronal nicotinic acetylcholine receptor (CHRNA7). The present study was designed to test the earlier linkage finding and to explore whether this susceptibility locus is involved in the epileptogenesis of a broader spectrum of IGE syndromes. Multipoint parametric and nonparametric linkage analyses with seven microsatellite polymorphisms encompassing the region of the CHRNA7 gene were performed using two diagnostic schemes of JME-related traits in two groups of multiplex families ascertained through probands with either JME (n = 27) or idiopathic absence epilepsy (n = 30). The present linkage study failed to replicate evidence for a major susceptibility locus for JME in the region encompassing the CHRNA7 gene. In addition, we found no hint in favor of linkage to 15q14 under the broad diagnostic scheme in any of the sets of families. If genetic variation in this region confers susceptibility to JME, then its effect size might be too small or its occurrence too rare to be detected in the investigated families.

Adolescent↗