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Biomedical subjects

G Fischer

Publications and source records attributed to G Fischer.

At least 55 records · Page 3Linked to original sources
PubMed2002

Myelopathy and sciatica induced by an extradural S1 root haemangioblastoma.

Haemangioblastomas are vascular tumours which mainly involve the central nervous system and retina, often in the setting of von Hippel-Lindau disease. Haemangioblastomas occurring outside the central nervous system are uncommon. Wherever it is, recognising this tumour prior to surgery is desirable, as preoperative embolisation may be considered. We report the clinical, imaging and pathological features of a sporadic sacral root haemangioblastoma in a 58-year-old man with chronic sciatica and myelopathy. The diagnosis was questioned preoperatively because an enlarged sacral foramen, seen to be filled by a highly vascular, enhancing mass and dilated vessels. Myelopathy was attributed to the presumed high venous pressure resulting from increased flow in veins draining the vascular tumour. Microneurosurgical excision was performed after endovascular embolisation and led to persistent clinical improvement.

Cerebellar Neoplasms↗
PubMed2002

[Geriatric assessment in family practice--results of concerted action by 7 European countries].

General practitioners are faced with the complex medical care of an increasing number of older people. Traditional demand led care is not able to provide optimal management for this age group, since it has been shown that many important health problems remain unknown or not optimally treated. Preventive geriatric assessment offers primary health care providers new opportunities to focus their management on the particular health problems of older people. A European concerted action involving seven countries formed to develop a "standard assessment for elderly people in primary care (STEP)". The aim was threefold: 1) to identify important and preventable health problems in old age, 2) to supply health care planners and providers with scientific evidence of the corresponding preventive procedures, and 3) to initiate a practical assessment framework for use in European primary care practices. Using a strict methodological protocol, 33 health problems were identified that potentially improve health outcomes in preventive programs for older people. A summary of the evidence is given for each of the included health areas. Taking the best available evidence, patients' preferences, and practice conditions into account, a preventive assessment program was developed containing validated and accepted instruments. The approach is algorithmic with a simple problem identification level and a further diagnostic stage. All recommended procedures are harmonized for common European use. An evidence-based preventive assessment program is expected not only to prevent disease and minimize disability and handicap, but it also offers health care planners a European data set of older peoples' needs for optimized resource allocation.

Aged↗
PubMed2002

Long-term outcome and quality of life of patients who are alive and in complete remission more than two years after allogeneic and syngeneic stem cell transplantation.

We assessed long-term outcome in 155 patients who had undergone an allogeneic/syngeneic stem cell transplant (SCT) and were in complete remission for more than 2 years after transplant. Probability of late transplant-related mortality was 6%, and affected only patients with chronic graft-versus-host disease (cGVHD). Thirteen percent of patients experienced relapse. Overall survival projected at 10 and 15 years was 83% and 76%, respectively. Secondary malignancies occurred in two patients, 7.5 and 11 years after SCT. Three female and four male patients parented children 19 to 84 months after SCT. Quality of life (QoL) was assessed in a cross-sectional study by the means of a 30-item questionnaire (QLQ-C30) of the EORTC. The questionnaire was sent to 127 patients remaining alive and answered by 106 patients. Seventy-three percent reported a good to very good QoL within 5 years after SCT and 78% after this time point. However, patients with cGVHD had significant impairment of physical, role and social functioning and only 60% of them were fit for work. These results from long-term survivors show that high cure rates with good to very good QoL can be achieved by allogeneic or syngeneic SCT.

Adolescent↗
PubMed2002

Further polymorphism of the MICA gene.

The MHC class I chain-related (MIC) gene family constitutes an interesting genetic group that is related to major histocompatibility complex (MHC) class I genes and is located within the MHC. The MIC gene products, MICA and MICB, have similar structures to HLA class I molecules. So far over 50 MICA alleles have been reported, which suggests that this genetic system is highly polymorphic. In order to investigate further the extent of MICA polymorphism we have studied exons 2-5 of the MICA gene in over 200 homozygous and heterozygous cell lines. Altogether we have identified 11 new MICA alleles and report 13 new nucleotide variations, one in exon 2, four in exon 3, four in exon 4, two in intron 1, one in intron 4 and one (a deletion) in exon 4. Eight of the 10 exonic variations are non-synonymous. The deletion in exon 4 leads to a frame-shift mutation and the introduction of a repeat of 12 leucine residues encoded by the microsatellite in exon 5. This study provides further evidence that the MICA gene is highly polymorphic. In contrast to MHC class I molecules, the polymorphic sites in MICA are predominantly within the alpha2 and alpha3 domains. The distribution of synonymous and non-synonymous substitutions suggests that there is selection for the polymorphic positions, which therefore define potential functional sites in the protein. We were also able to determine the association between MICA and HLA-B alleles in a number of homozygous cell lines bearing extended haplotypes.

Alleles↗
PubMed2002

Quality assurance and good laboratory practice in the mycological laboratory--compilation of basic techniques for the identification of fungi.

The identification of microfungi by morphology is generally regarded to be very difficult, as traits used for delimitation of species within a genus often show minute differences that can only be reliably evaluated by experienced mycologists. Different strains of one species can slightly vary in their morphology. This is often used as an argument by investigators with rather limited experience that identification on a morphological basis is not reliable and leads to inconsistent results. This paper compiles essential methods and techniques contributing to improved identification concerning (i) isolation from mixed cultures, (ii) inoculation and incubation, (iii) usage of media, (iv) identification and usage of determination keys, (v) preparation of microscopic slides, (vi) microscopy, and (vii) storage of isolates. The application of chemotaxonomy and sequencing for routine identification of airborne microfungi is shortly evaluated. The techniques compiled here can improve routine determination work considerably and will lead to much more accuracy and consistency of results. An improved quality assurance of applied fungal identification in the field of indoor and occupational hygiene is a prerequisite to find possible correlations between exposure on the one hand and health effects on the other.

Clinical Laboratory Techniques↗
PubMed2002

Pharmacological characterization of Ro 63-1908 (1-[2-(4-hydroxy-phenoxy)-ethyl]-4-(4-methyl-benzyl)-piperidin-4-ol), a novel subtype-selective N-methyl-D-aspartate antagonist.

Ro 63-1908, 1-[2-(4-hydroxy-phenoxy)-ethyl]-4-(4-methyl-benzyl)-piperidin-4-ol, is a novel subtype-selective N-methyl-D-aspartate (NMDA) antagonist that has been characterized in vitro and in vivo. Ro 63-1908 inhibited [(3)H]dizocilpine ((3)H-MK-801) binding in a biphasic manner with IC(50) values of 0.002 and 97 microM for the high- and low-affinity sites, respectively. Ro 63-1908 selectively blocked recombinant receptors expressed in Xenopus oocytes containing NR1C + NR2B subunits with an IC(50) of 0.003 microM and those containing NR1C + NR2A subunits with an IC(50) of >100 microM, thus demonstrating greater than 20,000-fold selectivity for the recombinant receptors expressing NR1C + NR2B. Ro 63-1908 blocked these NMDA NR2B-subtype receptors in an activity-dependent manner. Ro 63-1908 was neuroprotective against glutamate-induced toxicity and against oxygen/glucose deprivation-induced toxicity in vitro with IC(50) values of 0.68 and 0.06 microM, respectively. Thus, the in vitro pharmacological characterization demonstrated that Ro 63-1908 was a potent and highly selective antagonist of the NR2B subtype of NMDA receptors. Ro 63-1908 was active against sound-induced seizures (ED(50) = 4.5 mg/kg i.p. when administered 30 min beforehand) in DBA/2 mice. The dose required to give a full anticonvulsant effect did not produce a deficit in the Rotarod test. NMDA-induced seizures were also inhibited by Ro 63-1908 with an ED(50) of 2.31 mg/kg i.v. when administered 15 min before testing. Ro 63-1908 gave a dose-related neuroprotective effect against cortical damage in a model of permanent focal ischemia. Maximum protection of 39% was seen at a plasma concentration of 450 ng/ml. There were, however, no adverse cardiovascular or CNS side-effects seen at this dosing level.

Acoustic Stimulation↗
PubMed2002

Influence of the pulmonary annulus diameter on pulmonary regurgitation and right ventricular pressure load after repair of tetralogy of Fallot.

OBJECTIVE: To assess the influence of the pulmonary annulus diameter after reconstruction of the right ventricular (RV) outflow tract at repair of tetralogy of Fallot on pulmonary regurgitation and RV pressure load; and to evaluate the impact of pulmonary regurgitation on RV size and function. SETTING: Paediatric cardiology and diagnostic radiology departments of a tertiary referral centre. PATIENTS: 67 patients were examined at a median of 4.8 years after repair of tetralogy of Fallot by means of biplane angiocardiography and magnetic resonance imaging (MRI). MAIN OUTCOME MEASURES: Pulmonary annulus diameter and area, pulmonary regurgitant fraction, RV to left ventricular (LV) systolic pressure ratio, RV end diastolic volume, and RV ejection fraction were assessed. RESULTS: There was a significant positive correlation between pulmonary annulus area indexed to body surface area and pulmonary regurgitation (angiocardiography: r = 0.55, p < 0.001; MRI: r = 0.59, p < 0.001). No significant correlation was found between pulmonary annulus index and RV to LV systolic pressure ratio even in patients with small pulmonary annulus areas (r = -0.24, NS). Pulmonary regurgitant fraction was positively correlated with normalised RV end diastolic volume (angiocardiography: r = 0.42, p < 0.05; MRI: r = 0.56, p < 0.01). RV ejection fraction decreased with increasing pulmonary regurgitation (angiocardiography: r = -0.42, p < 0.05; MRI: r = -0.41, p < 0.05). CONCLUSIONS: The extent of pulmonary regurgitation after tetralogy of Fallot repair correlates with the postoperative size of the pulmonary annulus and is closely correlated with the enlargement of the RV. An enlargement of the pulmonary annulus to the second lower standard deviation of normal results in a decrease of pulmonary regurgitation and is sufficient to achieve adequate RV pressure unloading.

Adolescent↗
PubMed2001

[Cocaine abuse in maintenance therapy with methadone in narcotic dependent patients].

INTRODUCTION: From a clinical point of view, additional consumption of cocaine by methadone maintained patients seems to have increased during the last few years. In order to verify this clinical impression, we carried out a retrospective analysis about cocaine abuse by opioid-dependent patients undergoing methadone maintenance therapy at the drug addiction clinic, Department of Psychiatry, University of Vienna. METHODS: Supervised urinalysis was performed on a frequent basis in 160 patients during the investigational time frame of 1997 and 1999. Concomitant consumption of opioids, cocaine and benzodiazepines in urine toxicology results (n = 2242) was compared in a post hoc analysis. RESULTS: In 1997, 45% of urine toxicology tests were positive for opioids, 14.1% for cocaine and 22.1% for benzodiazepines. In 1999, however, 33.1% urine toxicology tests showed positive results for opioids, 22.2% for cocaine and 24% for benzodiazepines. It could be shown that the number of cocaine positive toxicology results increased significantly (p < 0.05) over the course of two years, and that the number of opioid positive tests decreased significantly (p < 0.05), whereas benzodiazepine consumption did not change. Age, and the duration of opioid dependence showed a significant influence on cocaine positive urinalysis. DISCUSSION: The significant increase of additional cocaine consumption in methadone maintained patients reflects the enhanced availability of the substance in Austria, as it has been shown in other European countries and the USA. In addition, evidence based treatment trials are needed to prove the efficacy of alternative opioid maintenance therapy and to evaluate whether cocaine consumption is less of a problem.

Adolescent↗
PubMed2001

The neuroprotective actions of FK506 binding protein ligands: neuronal survival is triggered by de novo RNA synthesis, but is independent of inhibition of JNK and calcineurin.

The immunosuppressant FK506 displays substantial neuroprotective and neuroregenerative effects. It is not fully understood to which extent these effects depend on the inhibition of the calcineurin phosphatase (PP2B). The present study has re-addressed this issue using Lie120, a novel highly specific inhibitor of calcineurin, which does not block the enzymatic activity of FKBPs or cyclophilins, respectively. We have determined the effect of FK506 (10-500 nM), V-10,367 (a FK506 derivative which does not block calcineurin; 1-5 microM) and Lie120 (a novel specific inhibitor of calcineurin, 0.1-5 microM) on the cellular survival and the pro-degenerative JNK activity of PC12 and Neuro2A cells following application of 200 microM H(2)O(2). FK506 and V-10,367, but not Lie120, protected both cell lines against H(2)O(2)-mediated death, whereas an increase in JNK1 activity was blocked by FK506 and Lie120, but not by V-10,367. Co-incubation of FK506 and V-10,367 with the mRNA synthesis inhibitor actinomycin D abolished the protective effect of FK506 and V-10,367. This antagonization was effective when actinomycin D was applied 30 min or 1 h, but not 2 or 4 h, after H(2)O(2) suggesting that FKBP-ligands confer their neuroprotection by rapid de novo synthesis of (functionally) anti-apoptotic proteins. The search for the corresponding effector genes revealed that the expression of FKBP25, FKBP38 and FKBP52 (analysis by reverse transcription-polymerase chain reaction (RT-PCR) did not change following H(2)O(2) or FK506, and this was also true for the expression of apoptosis-related genes caspase 3, bax, bcl-2 and bcl-xL (analysis by Multiplex-PCR). Summarizing, neuronal protection by FKBP-ligands is not mediated either by calcineurin or by JNK1 in this experimental set-up, whereas the FK506 mediated inhibition of JNK1 is realized by the inhibition of calcineurin, an effective activator of JNK1 in neurons.

Animals↗
PubMed2001

CD64 surface expression on neutrophils is transiently upregulated in patients with septic shock.

OBJECTIVE: To clarify the changes in total leukocyte counts, CD64 neutrophil receptor expression and serum granulocyte colony-stimulating factor (G-CSF) concentrations in critically ill patients without infection and sepsis and in patients with septic shock. DESIGN: Prospective study. SETTING: Intensive care unit (ICU) and research laboratory of a university hospital. PATIENTS: Eleven critically ill patients without infections and 22 patients with proven infections in septic shock for the first time and of at least 3 days' duration. MEASUREMENTS AND RESULTS: Over a 6month period, a longitudinal analysis of expression of the monomeric Fc receptor type I (CD64, FcgammaRI) on neutrophils was performed by flow cytometric analysis on a daily basis in all postoperative/post-traumatic patients admitted to the ICU until discharge from the ICU or death. Out of 273 patients, 11 patients without sepsis had organ failure and 22 patients with proven infections had septic shock for the first time and of at least 3 days' duration. Ten out of the 22 patients survived, 12 died. CD64 expression was greater in patients with septic shock than in patients without sepsis. Moreover, CD64 expression was only initially and transiently elevated in most survivors (9/10) and non-survivors (8/12) of septic shock. In survivors, G-CSF serum concentrations were markedly decreased in the 2nd week. CONCLUSIONS: Decreased neutrophil CD64 expression in an acutely ill population with septic shock may reflect the development of a non-responsive state as well as the early downregulation of neutrophil activation prior to the resolution of an ongoing infection.

Aged↗
PubMed2001

Reversible inhibition of calcineurin by the polyphenolic aldehyde gossypol.

The reversible inhibition of calcineurin (CaN), which is the only Ca(2+)/calmodulin-dependent protein Ser/Thr phosphatase, is thought to be a key functional event for most cyclosporin A (CsA)- and tacrolimus (FK506)-mediated biological effects. In addition to CaN inhibition, however, CsA and FK506 have multiple biochemical effects because of their action in a gain-of-function model that requires prior binding to immunophilic proteins. We screened a small molecule library for direct inhibitors of CaN using CaN-mediated dephosphorylation of (33)P-labeled 19-residue phosphopeptide substrate (RII phosphopeptide) as an assay and found the polyphenolic aldehyde gossypol to be a novel CaN inhibitor. Unlike CsA and FK506, gossypol does not require a matchmaker protein for reversible CaN inhibition with an IC(50) value of 15 microm. Gossypolone, a gossypol analog, showed improved inhibition of both RII phosphopeptide and p-nitrophenyl phosphate dephosphorylation with an IC(50) of 9 and 6 microm, respectively. In contrast, apogossypol hexaacetate was inactive. Gossypol acts noncompetitively, interfering with the binding site for the cyclophilin 18.CsA complex in CaN. In contrast to CsA and FK506, gossypol does not inactivate the peptidyl-prolyl-cis/trans-isomerase activity of immunophilins. Similar to CsA and FK506, T cell receptor signaling induced by phorbol 12-myristate 13-acetate/ionomycin is inhibited by gossypol in a dose-dependent manner, demonstrated by the inhibition of nuclear factor of activated T cell (NFAT) c1 translocation from the cytosol into the nucleus and suppression of NFAT-luciferase reporter gene activity.

Amino Acid Sequence↗
PubMed2001

Genomewide scans of complex human diseases: true linkage is hard to find.

Many "complex" human diseases, which involve multiple genetic and environmental determinants, have increased in incidence during the past 2 decades. During the same time period, considerable effort and expense have been expended in whole-genome screens aimed at detection of genetic loci contributing to the susceptibility to complex human diseases. However, the success of positional cloning attempts based on whole-genome screens has been limited, and many of the fundamental questions relating to the genetic epidemiology of complex human disease remain unanswered. Both to review the success of the positional cloning paradigm as applied to complex human disease and to investigate the characteristics of the whole-genome scans undertaken to date, we created a database of 101 studies of complex human disease, which were found by a systematic Medline search (current as of December 2000). We compared these studies, concerning 31 different human complex diseases, with regard to design, methods, and results. The "significance" categorizations proposed by Lander and Kruglyak were used as criteria for the "success" of a study. Most (66.3% [n=67]) of the studies did not show "significant" linkage when the criteria of Lander and Kruglyak (1995) were used, and the results of studies of the same disease were often inconsistent. Our analyses suggest that no single study design consistently produces more-significant results. Multivariate analysis suggests that the only factors independently associated with increased study success are (a) an increase in the number of individuals studied and (b) study of a sample drawn from only one ethnic group. Positional cloning based on whole-genome screens in complex human disease has proved more difficult than originally had been envisioned; detection of linkage and positional cloning of specific disease-susceptibility loci remains elusive.

Asthma↗
PubMed2001

Monomorphic molecules function as additional recognition structures on haptenated target cells for HLA-A1-restricted, hapten-specific CTL.

Hapten-specific T cells have been shown to recognize haptenated peptides with high avidity and, in some instances, with promiscuous MHC restriction. In this study, the impact of Ag density on MHC restriction of a CTL response specific to the trinitrophenyl (TNP) hapten was investigated. In this study, we demonstrate a novel recognition mechanism used by TNP-specific CD8(+) CTL in the presence of high Ag doses. Although low levels of TNP epitopes on target cells allowed for HLA-A1-restricted CTL activity only, entirely MHC-independent target cell recognition became operative at high TNP loading. In both cases, recognition was mediated by the TCR. This MHC-independent recognition is target cell type restricted and critically involves in our model direct recognition of the ectonucleotidase family surface molecule CD39 by the CTL.

Adenosine Triphosphatases↗
PubMed2001

Increased backbone flexibility in threonine45-phosphorylated hirudin upon pH change.

Protein phosphorylation on serine/threonine side chains represents a major regulatory event in the posttranslational control of protein functionality, where it is thought to operate at the level of structural changes in the polypeptide chain. However, key questions about molecular aspects of phosphate ester induced conformational alterations remain open. Among these concerns are the radius of action of the phosphate ester group, its effective ionic state, and its interplay with distinct bonds of the polypeptide chain. Primarily to define short-range effects upon threonine phosphorylation, the native 65 amino acid protein hirudin, conformationally restrained by a proline flanking the pThr(45) site and three intramolecular disulfide bonds, was structurally characterized in both the phosphorylated and the unphosphorylated state in solution. Circular dichroism and hydrogen exchange experiments (MALDI-TOF) showed that structural changes were caused by Thr(45)-Pro(46) phosphorylation only when the phosphate ester group was in its dianionic state. The spatial arrangement of the amino acids, monitored by 1H NMR spectroscopy, appears to be affected within a radius of about 10 A around the pThr(45)-OgammaH, with phosphorylation resulting in a loss of structure and increased flexibility within a segment of at least seven amino acid residues. Thus, the transition from the monoanionic to the dianionic phosphate group over the pH range 5.2-8.5 represents a general phosphorylation-dependent conformational switch operating at physiological pH values.

Amino Acid Sequence↗
PubMed2001

Direct measurement indicates a slow cis/trans isomerization at the secondary amide peptide bond of glycylglycine.

Spectral differences between the cis and the trans isomer of a secondary amide peptide bond were used to follow the time course of the cis/trans isomerization of Gly-Gly, Gly-Ala, Ala-Gly, and Ala-Ala dipeptides in the UV/vis region at 220 nm. Isomerization rates and Eyring activation energies were calculated from pH- and LiCl-mediated solvent jump experiments. Rate constants were found to be in a narrow range of 0.29 to 0.64 s(-)(1) for the zwitterionic dipeptides at 25 degrees C. The isomerization rate is about 2-fold higher for the monoionic forms of Gly-Gly. The zwitterionic Gly-Gly has an activation enthalpy DeltaH() of 71.6 +/- 4.9 kJ mol(-)(1) that is in the range of the rotational barriers of aromatic side chain dipeptides that have been measured by (1)H NMR magnetization transfer experiments. Late stages of protein backbone rearrangements often involve crossing the energy barrier for rotational isomerization of imidic peptide bonds. Our findings are consistent with the idea that a wide range of secondary amide peptide bonds are also able to induce slow rate-limiting steps in protein restructuring.

Dipeptides↗
PubMed2001

Differences in the expression of CD64 and mCD14 on polymorphonuclear cells and on monocytes in patients with septic shock.

The present study was performed to clarify the time course of the expression of CD64, the Fc gamma receptor type I (FcgammaR1), and membrane-bound CD14 (mCD14), one of the major receptors for endotoxin, on polymorphonuclear leukocytes (PMN) and monocytes in 22 postoperative/post-traumatic patients with septic shock. Therefore, the expression of CD64 and mCD14, and serum concentrations of granulocyte colony-stimulating factor (G-CSF) and interferon-gamma (IFN-gamma) were determined by flow cytometric analysis and enzyme-linked immunosorbent assay (ELISA), respectively, from the first day of septic shock onwards over a period of 14 days. When compared to the values of 12 healthy controls, CD64 expression was elevated significantly on PMN and monocytes of the patients, whereas the expression of mCD14 was decreased significantly at all days. The initially increased expression of CD64 on PMN and monocytes decreased within the first days of septic shock. The already initially decreased mCD14 expression decreased further on PMN, but not on monocytes. Serum concentrations of G-CSF and IFN-gamma during the study period were significantly higher than those of the control group. The differences in the kinetics of CD64 and mCD14 expression in patients with septic shock may be explained by different regulatory effects of cytokines, such as G-CSF and IFN-gamma.

Adult↗
PubMed2001

[Bank robbery as trauma--"but who understands me?"].

The different ways victims behave and feel after having experienced a bank robbery as well as some of the usual questions they may ask will be described using a typical case. The symptoms produced by a trauma do not only require a treatment based on empathy but also special attention. Should you ever have to deal with a traumatized victim of a robbery, the first and most important thing is not to leave the person alone. Simply talking to the person, without any reproaches may already help to calm him/her down. The most helpful thing is to involve the family, relatives and friends in further care. If the victim does not react when talking to him/her and counselling does not produce relief, then medication is advisable. If the persons have been taken hostage, or in the case of strong symptoms, it is advisable to seek the assistance of a psychologist or a psychiatrist. Therefore, dealing with victims after a bank robbery can be compared with a balancing act on a tightrope. A lot of sensitivity and patience are required.

Adult↗