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Biomedical subjects

G Fischer

Publications and source records attributed to G Fischer.

At least 181 records · Page 10Linked to original sources

Replication of the linear chromosomal DNA from the centrally located oriC of Streptomyces ambofaciens revealed by PFGE gene dosage analysis.

From a cosmid clone of Streptomyces ambofaciens containing the dnaA and gyrAB genes, a 2.7-kb self-replicating DNA fragment containing the chromosome replication origin oriC was isolated. This cosmid was previously maped physically to a region near the middle of the 8-Mb linear chromosomal DNA. A pulsed-field gel electrophoresis time-course analysis revealed that sequences flanking oriC were overrepresented relative to the rest of the chromosomal DNA during rapid growth, indicating that this origin is active. In addition, the terminal regions of the chromosomal DNA showed a slight overrepresentation at the onset of stationary phase.

Amino Acid Sequence↗

Transcatheter closure of atrial septal defects within the oval fossa: medium-term results in children using the 'ASDOS'-technique.

OBJECTIVES: The purpose of this study was to evaluate the safety and efficacy of the ASDOS-technique (Sulzer-Osypka GmbH, Germany) for transcatheter closure of atrial septal defects within the oval fossa. BACKGROUND: Although several attempts have been made to occlude defects within the oval fossa by transcatheter techniques, none of these has gained general acceptance. METHODS: Patients with a defect in the oval fossa measuring equal to or less than 20 mm diameter, with a residual septal rim of 5 mm or greater, body weight greater than 10 kg, with clinical indications for surgical closure were considered for transcatheter closure. Follow-up investigations were performed at discharge, after 1, 3, 6 and 9 months, as well as after 1 and 2 years. RESULTS: Of 78 patients considered for closure, a device was inserted in 41 patients (53%), with success being achieved in 40 patients (98%). The ages ranged from 1.1 to 15 years (7.8 +/- 1.92 years), the 'stretched' diameter of the defect from 10 to 20 mm (14.7 +/- 2.60 mm), and the diameters of the inserted devices from 25 to 45 mm (33.2 +/- 5.43 mm). Transient impairment of atrioventricular conduction occured in 4 patients. During the follow-up of 23.0 +/- 5.6 months elective surgical closure of a residual shunt was performed 26 months after insertion of the device in one patient. None of the other patients required surgery, hospitalisation or medical treatment, and none is requiring further treatment of the defect within the oval fossa. Fracture of one arm of the device occurred in 4 patients, but the fractured arms are in an unchanged and stable position after a period of at least 19 months. CONCLUSIONS: Our medium-term data show that transcatheter closure in children of defects within the oval fossa can be performed with a high efficacy and safety using the ASDOS-device.

Adolescent↗

Leukemia-free survival and mortality in patients with refractory or relapsed acute leukemia given marrow transplants from sibling and unrelated donors.

Between April 1982 and February 1997 39 patients (24 male, 15 female) with refractory acute leukemia and a median age of 31 years (19-51 years) received allogeneic marrow grafts from an HLA-identical sibling (n = 27), HLA-identical unrelated donor (MUD; n = 10) or 1-antigen mismatched unrelated donor (n = 2). Twenty-eight patients had acute myelogenous leukemia and 11 acute lymphoblastic leukemia. For conditioning most patients received total body irradiation combined with cyclophosphamide (n = 23) or etoposide (n = 7). For graft-versus-host disease prophylaxis patients received cyclosporin A (CsA) and methotrexate (MTX) (n = 20), MTX alone (n = 3), CsA and methylprednisone (n = 6), or CsA alone (n = 10), respectively. As of June 1997 probability of leukemia-free survival projected to 3 years after BMT was 14% for patients given sibling marrow grafts and 28% after MUD transplantation. Transplant-related mortality projected to 3 years was 32% after sibling and 37% after MUD marrow grafting. Although not significantly different, probability of relapse projected to 3 years after BMT was lower after MUD at 56% compared to 78% with sibling BMT. Thus, high-dose chemo/radiotherapy followed by allogeneic marrow infusion has a curative potential for patients with refractory leukemia and offers the chance of long-term disease-free survival for some patients.

Acute Disease↗

First comparative delineation of the T cell receptor repertoire in primary and multiple subsequent/coexisting metastatic melanoma sites.

At present, very little is known about the types and heterogeneity of T cell responses and immunodominant epitopes of melanoma-associated antigens at coexisting sites of primary melanoma and metastatic lesions. To address this issue, we compared the T cell receptor (TCR) gene usage, complementary-determining region 3 diversity, and melanoma-associated antigens expression patterns of primary and metastatic melanoma specimens from three patients with partially homologous HLA class-1 types. Results obtained showed an overall predominance of a very limited number of TCRV regions with AV13 and BV14 being most frequently overexpressed. Sequencing of the dominating TCR transcripts confirmed the restricted usage of certain TCR specificities and, in two of the three patients, identified several identical TCR clonotypes at more than one metastatic site. Nevertheless, we failed to detect TCR transcripts that were common to all tumor deposits in a given patient and, within the majority of coexisting metastases, tumor-infiltrating lymphocytes preferentially used individual site-specifically expanded TCR beta-chain VJ segment combinations. This occurrence of individual responses simultaneously executed at and influenced in their specificity by the different sites of tumor growth, has important implications for the type of strategies chosen in the development of efficacious vaccines for patients with metastatic melanoma.

Antibodies, Neoplasm↗

Quantification of cortisol inactivation in cirrhosis of the liver.

Impaired cortisol inactivation in patients with cirrhosis of the liver has been described, but precise data are limited and the pathophysiological significance of this finding has to be elucidated. Therefore, we assessed the main urinary cortisol metabolites using capillary gas chromatography and urinary free cortisol using an enzyme immunoassay in 20 consecutive patients with cirrhosis of the liver and in 28 healthy controls; ratios of cortisol inactivation were calculated (cortisol metabolites/cortisone metabolites, and sum of tetrahydrogenated cortisol metabolites/free urinary cortisol). In patients with cirrhosis free urinary cortisol was normal, whereas the sum of cortisol metabolites was significantly reduced; therefore, cortisol synthesis seems to be adequately adapted to the decreased hepatic inactivation (conjugation, ring A-reduction). A significantly reduced ratio of cortisol metabolites to cortisone metabolites indicating impaired renal 11beta-hydroxysteroid dehydrogenase activity was only found in a subgroup of patients with ascites.

11-beta-Hydroxysteroid Dehydrogenases↗

A scientific relational database combined with a report generator for endoscopy in networks: EndoNet.

BACKGROUND AND STUDY AIMS: The flexibility required in academic endoscopy units is not provided by the available database systems. In a project involving substantial cooperation between endoscopists and computer scientists, we have developed an adaptable database, combined with a report generator embedded in the hospital's intranet. PATIENTS AND METHODS: Six workstations in different areas of the hospital were clustered with a UNIX operating system to implement multi-user capability and access control. A relational database was used to design an application appropriate to the specific needs of the endoscopy unit in a teaching hospital engaged in scientific research. Both the terminology used in standardized endoscopy nomenclature and a free text block facility were included. A graphical user interface was developed to assemble pertinent data, generate the reports, and supervise the database. RESULTS: A total of 4936 examinations including 2988 patients were entered consecutively during continuous routine operation of the system. Complete report generation required five minutes (median; range 1-9 minutes). Both structured items and free text were used in all the reports. Querying of the database was possible, concerning matters such as the need for repeated endoscopic therapy in acute gastrointestinal bleeding (4%), the search for Helicobacter pylori in appropriate patients (64%), the rate of accidental pancreatic duct visualization in endoscopic retrograde cholangiography (24%), and links between examinations and active trials (2%). Indicating improved report quality, the number and the diameter of esophageal varices in patients with varices were more frequently reported with the new report system than with previous typed reports (P<0.001). An anonymous questionnaire revealed that the readability of the computer-generated reports was better than that of the previous typewritten reports (P=0.01). CONCLUSIONS: This report describes the creation of a database application and a report generator meeting the needs of scientific and routine use, and the successful application of this system in an academic endoscopy unit.

Computer Communication Networks↗

Double-blind trial of omeprazole and amoxicillin in the cure of Helicobacter pylori infection in gastric ulcer patients. The Ulcer Study Group, Germany.

BACKGROUND: Our aim was to investigate the efficacy of omeprazole and amoxicillin in curing Helicobacter pylori infection in gastric ulcer patients. METHODS: In a double-blind trial 185 H. pylori-positive gastric ulcer patients were prospectively randomized to receive 40 mg omeprazole twice daily and either 750 mg amoxicillin three times daily or 750 mg amoxicillin placebo three times daily on days 1-14, followed by 20 mg omeprazole daily on days 15-56. RESULTS: Twenty-seven patients were excluded because of lack of compliance or missed follow-up examinations; one patient receiving amoxicillin discontinued treatment owing to side effects. On an intention-to-treat basis, omeprazole/amoxicillin led to cure of H. pylori infection in 67.1% (47 of 70) of patients not using non-steroidal anti-inflammatory drugs (NSAIDs)/aspirin (ASA) and in 46.7% (14 of 30) of those taking NSAIDs/ASA (P < 0.05). With the omeprazole/placebo regimen, H. pylori infection was cured in 8.8% (no NSAIDs), and 0% (NSAIDs). CONCLUSIONS: The use of NSAIDs/ASA may limit the efficacy of omeprazole/amoxicillin in curing H. pylori infection in gastric ulcer patients.

Adolescent↗

Giant cephalhaematoma in a 17-year-old boy with Ehlers-Danlos syndrome.

We report a case of giant cephalhaematoma in a 17-year-old boy with Ehlers-Danlos syndrome. This haematoma occurred after a minor head injury. It increased in size, immediately after needle aspiration and was responsible for considerable blood loss. Possible physiopathological mechanisms and treatment modalities are discussed.

Adolescent↗

Conserved sequence motifs of CDR3 loops of TCR specific for two major epitopes of the grass pollen allergen PhI p 1.

We analyzed the cDNA sequence data of complementarity determining regions (CDR3) of epitope mapped alphabeta TCR of T cell clones (TCC). The TCC were specific for the major timothy grass (Phleum pratense) pollen allergen Phl p 1 and were derived from the peripheral blood of seven unrelated grass pollen-allergic individuals. Each TCR recognized one of two immunodominant T cell epitopes, PP73 or PP103, of Phl p 1. Although a diversity of recombined V and J segments was observed, amino acid motifs as long as five residues were conserved among CDR3 loops of TCR from TCC of different atopic individuals specific for the same peptide. The conserved sequences could comprise as much as 60% of the CDR3. All amino acid residues of the motifs of the CDR3beta and most of the CDR3alpha of all TCR used in this study were encoded by randomly added nucleotides. This indicates that they were specifically selected for by the peptide bound to the MHC class II molecule. For one selected patient, a larger number of TCC, specific for PP103, was analyzed. The TCR repertoire was limited to three different TCR. The same MHC class II molecule, DRB1*1301, was identified to present PP103 to each of the three TCR.

Allergens↗

Airborne fungi and their secondary metabolites in working places in a compost facility.

The present study investigates in detail the exposure to airborne fungal spores in working places in compost facilities. The fungal species composition in the air is compared with the spectrum of microbial metabolites with regard to the physiological properties of different fungal species. The results indicate that the spectrum of microbial volatile organic compounds (MVOCs) and the production of mycotoxins can be specific for certain species. In addition to the pathogenic and allergological relevance, the fungi may have different toxicological health impacts.

Air Microbiology↗

[Airborne molds and their metabolites at workplaces in composting plants].

Airborne fungal contaminants in composting facilities gain more and more importance in regard to health hazards for workers and an emission of spores and microbial metabolites in the environment. Possible health impacts of bioaerosols are widely discussed from both an allergological and a toxicological point of view. The present study investigates in detail the exposure to airborne fungal spores at working places in compost plants. These fungal spores are compared to the spectrum of microbial volatile metabolites with regard to the physiological properties of each fungal species. The results indicate, that the spectrum of microbial volatile organic compounds (MVOC) as well as the production of mycotoxins can be specific for certain species. In addition to the pathogenic and allergological relevance, the fungi may have different toxicological health impacts. However, an evaluation of health effects caused by the great variety of volatile organic compounds remains difficult, since information on their toxicological impact is lacking.

Air Microbiology↗

Outpatient opiate detoxification treatment with buprenorphine. Preliminary investigation.

In an open study design, 50 opioid-dependent subjects (DSM-IV: 304. 0) were investigated in a gradual detoxification treatment with buprenorphine. The study was performed at the drug addiction outpatient clinic of the Department of General Psychiatry at the University of Vienna. Subjects had to contact the outpatient clinic on a daily basis and buprenorphine was administered according to their clinical status. Withdrawal symptoms were evaluated by applying the WANG scale. Urine samples were screened for drug toxicology to exclude additional consumption. In this investigation buprenorphine was applied sublingually in a free dosage scheme aimed at completing detoxification treatment within 10 days by reducing buprenorphine on a daily basis. A mean daily dosage of 2.3 mg buprenorphine was required by patients on day 1 of the treatment period. The highest mean daily buprenorphine dosage was given on day 2, followed by a daily reduction over the study period. The result of this open study design revealed that a gradual daily reduction of buprenorphine might be a successful alternative outpatient detoxification treatment in opioid-dependent subjects. Compliance was 70%, the reported and evaluated withdrawal symptoms during the study period were moderate.

Adult↗

The unified biosocial model of personality in schizophrenia families and controls.

This report describes the application of a unified biosocial model of personality developed by C.R. Cloninger to a sample of families identified through a proband with schizophrenia and a sample of controls. Families of schizophrenic patients were ascertained in USA and Austria. We could detect differences between females and males in their response to positive reinforcement (Reward Dependence) and differences between young and old people with respect to the response to new and/or exciting situations (Novelty Seeking). In general, results obtained for individuals from schizophrenia families and controls were similar. These results are not substantially influenced by psychiatric disorders in individuals. Psychiatric diagnosis may have an influence on the third dimension of Cloninger's model, designated Harm Avoidance. Analysis showed that patients with a diagnosis of schizophrenia or from the schizophrenia spectrum try harder to avoid punishment or aversive stimuli than family members with another psychiatric disorder or without a psychiatric diagnosis as well as controls. The results are promising and further research is needed to evaluate the structure of the proposed personality model in families and the relationship of personality to psychiatric status.

Adult↗

Comparison of buprenorphine and methadone maintenance in opiate addicts.

As a maintenance agent for opioid dependency, buprenorphine offers advantages such as a lower level of dependence and minimal withdrawal symptoms, due to its partial agonist properties at the micro-opioid receptor. Previous studies have shown 8 mg sublingual buprenorphine to be equivalent to 60 mg oral methadone in terms of retention rate and opioid-negative urine levels. In a 24-week, ongoing European study, 34 opioid-dependent subjects were assessed; 16 receiving buprenorphine and 18 methadone. A free dosing schedule was used with no upper limit for methadone dosing but with a maximum buprenorphine dose of 8 mg. Screening prior to the study excluded subjects with polysubstance dependence, somatic disease and/or HIV infection. Primary outcome measures were abstinence from other drugs, for which subjects provided weekly urine samples for analysis of opioids, cocaine and benzodiazepines, and retention in treatment. Patients in the buprenorphine group provided a greater proportion of negative urine samples, in particular cocaine-negative samples, compared with the methadone group, although this was not statistically significant. Retention in the buprenorphine group was significantly lower than in the methadone group, suggesting that the 8 mg buprenorphine limit may have biased the results in favour of methadone, and that this dose may have been too low for those subjects with high levels of dependence. However, buprenorphine is clearly effective in the more motivated subjects and further investigation in this subgroup is recommended.

Adolescent↗

Buprenorphine maintenance in pregnant opiate addicts.

Opioid maintenance agents such as methadone and slow-release morphine have provided beneficial effects in pregnant opioid-dependent women in both themselves and their child. However, one of the major drawbacks involved with these agents is that they cause an increase in the severity of neonatal abstinence syndrome (NAS) when compared to mothers using heroin. Consequently, a trial was performed to investigate the effects of buprenorphine use during pregnancy. A total of nine pregnant opioid-dependent women were transferred from either a mean daily dose of 39.7 mg methadone or 400 mg slow-release morphine to a mean daily dose of 8.1 mg buprenorphine. The buprenorphine-maintained patients were integrated into an already established outpatient maintenance treatment programme covering all aspects of prenatal and perinatal care. Results demonstrated that buprenorphine administration in opioid-dependent pregnant patients is efficacious and well tolerated. Babies born to buprenorphine-maintained patients had birthweight and Apgar scores within the normal range (2,500-4,500 g and 9-10, respectively) and no evidence of opioid-related NAS was observed. The results from this preliminary study indicate the potential for buprenorphine maintenance therapy in pregnant addicts, although further research is required to confirm this hypothesis.

Adult↗

Prolyl isomerases do not catalyze isomerization of non-prolyl peptide bonds.

Prolyl isomerases accelerate the cis <--> trans isomerization of prolyl peptide bonds during protein folding and probably also in folded proteins. We asked whether this catalytic function is in fact restricted to prolyl bonds or whether the isomerizations of 'normal' non-prolyl peptide bonds are catalyzed as well. By using the P39A variant of ribonuclease T1 as a substrate we find that the trans --> cis isomerization of the Tyr38-Ala39 bond in the refolding of this protein is not catalyzed by prolyl isomerases of the cyclophilin, FKBP and parvulin families. These enzymes are neither able to catalyze amide bond isomerizations in the proline-free model peptide Ala-Ala-Tyr-Ala-Ala.

Amides↗

Semiautomated microtiter plate assay for monitoring peptidylprolyl cis/trans isomerase activity in normal and pathological human sera.

An UV/VIS spectrophotometric assay technique was developed that was able to routinely monitor peptidylprolyl cis/trans isomerase (PPIase) activity of biological fluids in 96-well microtiter plates. The assay, based on monitoring the cis-to-trans isomerization of succinyl-Phe-cisPro-Phe-4-nitroanilide as substrate in a chymotrypsin-coupled reaction, yields a throughput of 96 samples per 30 min. The assay's capacity was exemplified by dealing with the PPIase activity in several normal and pathological human sera. Reference values of 151 healthy subjects (83 females, 69 males, 17 to 60 years old) were found to possess significant sex-specific differences. PPIase activity factor K of the sera was significantly greater in males (5th, 50th, 95th percentiles: 17, 36, 55 K) than females (14, 30, 48 K). PPIase activities of sera from healthy donors (n = 151) were significantly higher (Mann-Whitney rank-sum test P < 0.0001) than those of patients (n = 47). PPIase activity in serum samples stored at 4 degrees C was stable for at least 20 h.

Acute Disease↗