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Biomedical subjects

G Fischer

Publications and source records attributed to G Fischer.

At least 109 records · Page 6Linked to original sources
PubMed2000

Treatment of opioid-dependent pregnant women with buprenorphine.

AIMS: To assess the maternal and fetal acceptability of buprenorphine and neonatal abstinence syndrome (NAS) in children born to buprenorphine-maintained mothers. DESIGN AND SETTING: Open-label, flexible dosing, inpatient induction with outpatient maintenance, conducted at the University of Vienna within the existing pregnancy and drug addiction program. PARTICIPANTS: Fifteen opioid-dependent pregnant women. INTERVENTION: Sublingual buprenorphine tablets (1-10 mg/day). MEASUREMENTS: Mothers: withdrawal symptoms (Wang Scale), nicotine dependence (Fagerström Scale: FTQ) and urinalysis. Neonates: birth outcome and NAS (Finnegan Scale). FINDINGS: All subjects were opioid-, nicotine- and cannabis-dependent. Buprenorphine was well tolerated during induction (Wang Score < or = 4) and illicit opioid use was negligible (91% opioid-negative). All maternal, fetal and neonatal safety laboratory measures were within normal limits or not of clinical significance. Mean birth outcome measures including gestational age at delivery (39.6 +/- 1.5 weeks), Apgar scores (1 min = 8.9; 5 min = 9.9; and 10 min = 10), birth weight (3049 +/- 346 g), length (49.8 +/- 1.9 cm) and head circumference (34.1 +/- 1.8 cm) were within normal limits. The NAS was absent, mild (without treatment) and moderate (with treatment) in eight, four and three neonates, respectively. The mean duration of NAS was 1.1 days. CONCLUSIONS: Buprenorphine appears to be well accepted by mother and fetus, and associated with a low incidence of NAS. Further investigation of buprenorphine as a maintenance agent for opioid-dependent pregnant women is needed.

Buprenorphine↗
PubMed2000

Regeneration of erythropoiesis after related- and unrelated-donor BMT or peripheral blood HPC transplantation: a major ABO mismatch means problems.

BACKGROUND: Blood group incompatibility in allogeneic BMT is common but does not appear to affect the outcome in terms of incidence of graft rejection or delayed engraftment. However, major ABO incompatibility may be associated with prolonged erythroid aplasia. STUDY DESIGN AND METHODS: In a retrospective analysis of 286 allogeneic transplant recipients, the prevalence of prolonged erythroid aplasia, including pure RBC aplasia, was determined. RESULTS: Patients receiving major ABO-incompatible grafts showed a significant delay in reticulocyte engraftment (median, 32 days; range, 12-347) from that in patients receiving ABO-identical (20; 10-152) or minor ABO-incompatible (21; 12-47) grafts. Pure RBC aplasia occurred in 7 (3%) of 240 evaluable recipients and was observed only in the major ABO-incompatible group (7/43, 16%). Treatment of pure RBC aplasia consisted of either plasma exchange, which resulted in a response within 16 to 68 days, or immunoadsorption, in which the response occurred between Days 119 and 204 after initiation of treatment. CONCLUSION: Major ABO incompatibility may lead to delayed reticulocyte engraftment, resulting in prolonged transfusion dependency and increased risks of transmission of infection and iron overload. Therefore, therapeutic strategies should be taken into consideration to allow erythroid reconstitution in these patients.

ABO Blood-Group System↗
PubMed2000

Exposure to airborne fungi, MVOC and mycotoxins in biowaste-handling facilities.

Health impacts due to fungi in indoor air can only be estimated reliably, if both fungal propagules and fungal secondary metabolites are qualified and quantified. In the present study, the fungal species composition in a compost facility is compared to the spectrum of microbial metabolites in the air with regard to the physiological properties of different fungal species. A number of relevant fungi was tested for the production of both volatile and non-volatile metabolites on different substrata. The profiles of mycotoxins and microbial volatile organic compounds (MVOC) turned out to be specific for certain species in pure culture. Consequently, the fungi may have different toxicological health impacts, though information on the relevance of microbial volatiles is still limited.

Air Microbiology↗
PubMed2000

Species-specific profiles of mycotoxins produced in cultures and associated with conidia of airborne fungi derived from biowaste.

The potential to produce mycotoxins and non-volatile secondary metabolites was investigated for approximately 250 freshly isolated fungal strains. Among the eleven most relevant species, viz. Aspergillus flavus, A. fumigatus, A. niger, A. parasiticus, A. versicolor, Emericella nidulans, Paecilomyces variotii, Penicillium brevicompactum, P. clavigerum, P. crustosum, and P. polonicum, a wide range of metabolites partly of toxicological relevance was identified. Several unknown metabolites were found for the less frequent species, which were primarily investigated for chemotaxonomic delimitation from closely related species. The spectra of metabolites in conidial extracts and culture extracts (containing also mycelium and medium) were compared for a limited number of relevant fungi. Some mycotoxins, such as sterigmatocystin in Emericella nidulans, were not present in the conidial extracts, though produced by most strains. Fumigaclavine C, tryptoquivaline, and trypacidin, characteristic for A. fumigatus, were found in conidial extracts, but highly toxic compounds such as gliotoxin and fumitremorgens were not present. Finally, compounds such as cyclopenol, cyclopenin, and penitrem A being characteristic for certain penicillia, were found in conidial extracts and are therefore assumed to occur in native bioaerosols.

Air Microbiology↗
PubMed2000

Oxygen stress increases prolyl cis/trans isomerase activity and expression of cyclophilin 18 in rabbit blastocysts.

The peptidyl-prolyl cis/trans isomerase (PPIase) activity and the expression of cyclophilins were studied in 6-day-old rabbit preimplantation embryos cultured under physiological and increased oxygen concentrations of 5% and 20% O(2), respectively. The PPIase activity was completely inhibited by cyclosporin A (CsA). The inhibitor of FK506-binding proteins, rapamycin, had no effect on the PPIase activity, indicating that the PPIase activity in rabbit blastocysts originates from cyclophilins. Using CsA affinity chromatography, only one cyclophilin with a molecular mass of about 17.8 kDa was separated. The cDNA of rabbit cyclophilin was cloned and sequenced. Analysis of the 682-base pair cDNA revealed an open reading frame coding for a polypeptide of 164 amino acid residues with a molecular weight of 17.83 kDa. Homologies of 90% and 96% for the cDNA and amino acid sequence, respectively, to the human CyP18 were found, suggesting that the novel rabbit cyclophilin is a member of the CyP18 family (rabCyP18). The transcription level of rabCyP18 mRNA was 8.3 +/- 0.6 pg in 100 ng total RNA in noncultured blastocysts. In vitro culture with moderate oxygen stress (20% O(2)) resulted in a 1.5-fold increase in rabCyP18 transcription and an increased PPIase activity compared to that of blastocysts cultured with 5% O(2). Increase in transcription rate and PPIase activity by oxygen stress suggests an involvement of CyP18 in oxygen defense in rabbit preimplantation embryos.

Amino Acid Sequence↗
PubMed2000

Assisted folding of D-glyceraldehyde-3-phosphate dehydrogenase by trigger factor.

The Escherichia coli trigger factor is a peptidyl-prolyl cis-trans isomerase that catalyzes proline-limited protein folding extremely well. Here, refolding of D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the presence of trigger factor was investigated. The regain of activity of GAPDH was markedly increased by trigger factor after either long- or short-term denaturation, and detectable aggregation of GAPDH intermediates was prevented. In both cases, time courses of refolding of GAPDH were decelerated by trigger factor. The reactivation yield of GAPDH showed a slow down-turn when molar ratios of trigger factor to GAPDH were above 5, due to tight binding between trigger factor and GAPDH intermediates. Such inactive bound GAPDH could be partially rescued from trigger factor by addition of reduced alphaLA as competitor, by further diluting the refolding mixture, or by disrupting hydrophobic interactions in the complexes. A model for trigger factor assisted refolding of GAPDH is proposed. We also suggest that assisted refolding of GAPDH is due mainly to the chaperone function of trigger factor.

Enzyme Activation↗
PubMed2000

A bidomain model based BEM-FEM coupling formulation for anisotropic cardiac tissue.

A hybrid boundary element method (BEM)/finite element method (FEM) approach is proposed in order to properly consider the anisotropic properties of the cardiac muscle in the magneto- and electrocardiographic forward problem. Within the anisotropic myocardium a bidomain model based FEM formulation is applied. In the surrounding isotropic volume conductor the BEM is adopted. Coupling is enabled by requesting continuity of the electric potential and the normal of the current density across the boundary of the heart. Here, the BEM part is coupled as an equivalent finite element to the finite element stiffness matrix, thus preserving in part its sparse property. First, continuous convergence of the coupling scheme is shown for a spherical model comparing the computed results to an analytic reference solution. Then, the method is extended to the depolarization phase in a fibrous model of a dog ventricle. A precomputed activation sequence obtained using a fine mesh of the heart was downsampled and used to calculate body surface potentials and extracorporal magnetic fields considering the anisotropic bidomain conductivities. Results are compared to those obtained by neglecting in part or totally (oblique or uniform dipole layer model) anisotropic properties. The relatively large errors computed indicate that the cardiac muscle is one of the major torso inhomogeneities.

Animals↗
PubMed2000

Prevalence and distribution of hepatitis C subtypes in patients with opioid dependence.

UNLABELLED: AIM AND SETTING: The drug addiction out-patient clinic at the University Hospital for Psychiatry in Vienna performed a study to identify the prevalence of hepatitis C virus (HCV) infections in a group of opiate-dependent patients, to detect the distribution of HCV subtypes and to calculate the comorbidity of human immunodeficiency virus (HIV) and hepatitis B virus (HBV). DESIGN AND PARTICIPANTS: We consecutively investigated unselected patients (n = 173) during an observation period of 2 months with the diagnosis of opioid dependence (DSM-IV: 304.0) and polysubstance dependence (DSM-IV: 304.9). MEASUREMENTS: Blood was investigated focusing on liver enzymes and on viral status including HIV, hepatitis B and hepatitis C, followed by subtyping of the virus. FINDINGS: In 80.3% hepatitis C antibodies were found, 66.5% were HCV RNA (PCR) positive. 3a was the most frequent subtype (35.6%), followed by 1a (28.8%) and 1b (22.0%). Four patients had both subtypes 1a and 1b (6.8%), 3 were 2b positive (5.1%) and 1 patient had subtypes 2a/2c (1.7%). No significant difference in aspartate (AST) and alanine aminotransferases (ALT) concerning the different subtypes (AST: p = 0.290; ALT: p = 0.260) could be calculated; 11.6% showed co-infection with HIV, 2 patients had a chronic infection with hepatitis B. CONCLUSIONS: The rate of HCV infection in substance-dependent patients at our drug addiction out-patient clinic is extremely high. The distribution of subtypes showed a relatively homogeneous distribution of the types 1a, 1b and 3a. The recommended therapy with alpha-interferon should be initiated in drug-dependent patients under considerations of an enrollment in oral maintenance with synthetic opioids.

Adolescent↗
PubMed2000

Improved platelet counting using two-dimensional laser light scatter.

Clinical management of platelet disorders depends on accurate platelet counts. We evaluated a new analytic approach for platelet counting based on improved platelet discrimination. Current automated counting methods provide accurate platelet counts for most samples but often are unable to discriminate platelets accurately from nonplatelet particles such as microcytic RBCs, RBC fragments, and cellular debris that may falsely elevate platelet counts. The new approach measures 2 light-scatter angles of platelets and nonplatelet particles as they pass through a laser beam. The volume and refractive index of each platelet and particle are derived from the light-scatter measurements using the Mie scattering theory. Together, these 2 measurements provide improved platelet discrimination compared with 1-dimensional methods. With its improved discrimination, 2-dimensional platelet analysis provides more accurate platelet counts in samples containing interfering particles and may contribute to more effective clinical management of patients with platelet disorders.

Blood Platelet Disorders↗
PubMed2000

Vulvitis attributed to hypersensitivity to estrogen. A report of 11 cases.

BACKGROUND: Vulvitis that is refractory to all treatment remains a therapeutic challenge. Hypersensitivity to progesterone and estrogen has been recognized as a rare cause of premenstrual dermatoses. Such hypersensitivity seemed to be the cause of vulvitis in the patients described below. CASES: Nine women had treatment-resistant cyclic vulvitis and two patients had vulvitis develop after commencing hormone replacement therapy (HRT). These patients demonstrated delayed-type hypersensitivity responses by intradermal testing to endogenous estrogens, with two of the patients also reacting to intradermal testing with progesterone. A group of 19 healthy control subjects with no history of vulvar symptoms did not react to any test substance. Ten subjects with other vulvar dermatoses also did not react to any test substance. Of the nine patients with cyclic vulvitis, one recovered at menopause, and three responded to therapy aimed at lowering endogenous estrogen levels. One was able to control symptoms with a potent topical corticosteroid, and four elected not to be treated. Both patients with HRT-related vulvitis recovered when HRT was ceased. CONCLUSION: Hypersensitivity to estrogen appears to be implicated in chronic, cyclic vulvitis and vulvitis related to HRT in these patients. This is the first report of vulvitis due to estrogen hypersensitivity. The problem may not be rare and should be considered in patients with unexplained cyclic vulvitis unresponsive to standard therapy or in those developing noncandidal vulvitis on HRT. Specific therapy aimed at suppressing or antagonizing estrogen may be required in these patients.

Adolescent↗
PubMed2000

Functionalized and [a]-anellated carbazoles as potential B-DNA ligands: experimental studies of DNA binding and molecular modeling of intercalation complexes.

Three synthetically available carbazole derivatives 3-5 were investigated for DNA binding (ethidium bromide displacement assay, DNA unwinding assay), for inhibition of topoisomerase I and for cell cytotoxicity (antitumour cell lines). In addition molecular modeling studies of DNA complexes were performed by semiempirical quantum chemistry, force field calculations and molecular dynamics calculations. In summary, combining the results from experiments and molecular modeling, the naphthoquinone anellated carbazole 4 emerges as a promising antitumour active candidate for further drug design studies in carbazole chemistry.

Animals↗
PubMed1999

Intraclonal polymorphism in the bacterium Streptomyces ambofaciens ATCC23877: evidence for a high degree of heterogeneity of the wild type clones.

In Streptomyces ambofaciens a genetic instability generates a high degree of polymorphism consisting of four main phenotypes: pigmented colonies (Pig(+) qualified as WT phenotype), pigment-defective colonies, pigmented colonies with pigment-defective sector and pigmented colonies with pigment-defective papillae. Molecular analysis of Pig(col)(-) and Pig(sec)(-) (pigment-defective mutant derived from a colony and a sector, respectively) produced by genetic instability and isolated in five Pig(+) subclones progenies revealed a new aspect of polymorphism in S. ambofaciens ATCC23877. Frequencies of Pig(col)(-) and Pig(sec)(-) mutants deleted at the chromosome ends varied from one WT progeny to another. Two main types of deleted mutants were observed: deleted for one or both chromosomal extremities. The relative proportion of these two categories differed according to the WT progeny. These results argue for heterogeneity of the WT clones, i.e., Pig(+) colonies, originated from S. ambofaciens ATCC23877.

Chromosomes, Bacterial↗
PubMed1999

Synthesis and cytotoxic evaluation of cycloheximide derivatives as potential inhibitors of FKBP12 with neuroregenerative properties.

On the basis of the new finding that the protein synthesis inhibitor cycloheximide (1, 4-[2-(3, 5-dimethyl-2-oxocyclohexyl)-2-hydroxyethyl]-2,6-piperidinedione) is able to competitively inhibit hFKBP12 (K(i) = 3.4 microM) and homologous enzymes, a series of derivatives has been synthesized. The effect of the compounds on the activity of hFKBP12 and their cytotoxicity against eukaryotic cell lines (mouse L-929 fibroblasts, K-562 leukemic cells) were determined. As a result, several less toxic or nontoxic cycloheximide derivatives were identified by N-substitution of the glutarimide moiety and exhibit IC(50) values in the range of 22.0-4.4 microM for inhibition of hFKBP12. Among these compounds cycloheximide-N-(ethyl ethanoate) (10, K(i) = 4.1 microM), which exerted FKBP12 inhibition to an extent comparable to that of cycloheximide (1), was found to cause an approximately 1000-fold weaker inhibitory effect on eukaryotic protein synthesis (IC(50) = 115 microM). Cycloheximide-N-(ethyl ethanoate) (10) was able to significantly speed nerve regeneration in a rat sciatic nerve neurotomy model at dosages of 30 mg/kg.

Animals↗
PubMed1999

Polypeptide flux through bacterial Hsp70: DnaK cooperates with trigger factor in chaperoning nascent chains.

A role for DnaK, the major E. coli Hsp70, in chaperoning de novo protein folding has remained elusive. Here we show that under nonstress conditions DnaK transiently associates with a wide variety of nascent and newly synthesized polypeptides, with a preference for chains larger than 30 kDa. Deletion of the nonessential gene encoding trigger factor, a ribosome-associated chaperone, results in a doubling of the fraction of nascent polypeptides interacting with DnaK. Combined deletion of the trigger factor and DnaK genes is lethal under normal growth conditions. These findings indicate important, partially overlapping functions of DnaK and trigger factor in de novo protein folding and explain why the loss of either chaperone can be tolerated by E. coli.

Bacterial Proteins↗