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Biomedical subjects

D Winkler

Publications and source records attributed to D Winkler.

At least 37 records · Page 2Linked to original sources
PubMed2003

Improving planning procedure in brain biopsy: coupling frame-based stereotaxy with navigational device STP 4.0.

37 consecutive patients with space-occupying intracerebral lesions were operated via frame-based stereotaxy. After CT-localizing of suspect lesions and computer-supported definition of entry and target coordinates a serial stereotactic biopsy was performed. Biopsy specimens allowed a satisfactory neuropathological examination and diagnostic result in 36 cases (97 %). Only three patients (8.1 %) showed an intraoperative bleeding, which was not associated with any postoperative CT-detectable hematoma, neurosurgical intervention nor with any neurological deficits. In summary we described the method of a computerized planning technique for stereotactic biopsy with the use of a special stereotactic planning program. High percentage of satisfactory neuropathological diagnoses and comfortable and accurate definition of target and entry coordinates justify computer support as a routine method.

Adolescent↗
PubMed2002

[Seasonal affective depression in 2 German speaking university centers: Bonn, Vienna. Clinical and demographic characteristics].

Six hundred ten patients with seasonal affective disorder (SAD) were diagnosed and treated at the university hospitals for psychiatry in Bonn, Germany (1989-1992) and Vienna, Austria (1993-2001). The aim of this study was to compare our sample with other SAD populations in the literature and to investigate differences between the two study locations. We found female:male sex ratios of 5.0:1.0 in unipolar depressives and 1.5:1.0 in patients with bipolar affective disorder. Of our patients, 21.7% suffered from bipolar II disorder, and 1.3% were diagnosed as having bipolar I. Our patients obtained a mean global seasonality score (GSS) of 15.4. Women had a higher GSS than men (t = 2.127, P = 0.035), and Viennese patients had higher scores than patients in Bonn (t = 3.104, P = 0.002). Totals of 66.3% of all patients suffered from atypical depression and 17.8% from melancholic depression. Patients with atypical depression were more frequent in Vienna, whereas patients with melancholic depression predominated in Bonn (chi 2 = 54.952, df = 2, P < 0.001). The demographic and clinical characteristics of the patients described in this article confirm the findings of other epidemiological investigations obtained in non-German-speaking samples.

Adult↗
PubMed2002

Changes of clinical pattern in seasonal affective disorder (SAD) over time in a German-speaking sample.

OBJECTIVE: The goals of this study are to provide estimates of clinical and demographic variables of patients with seasonal affective disorder (SAD) in Germany and Austria, to compare our results with those of previously published SAD studies, and to find out whether the clinical pattern of SAD remained stable over several years. METHOD: We investigated 610 SAD patients from the outpatient clinics in Bonn (n = 190) and Vienna (n = 420). Patients in Bonn were recruited in the fall-winter season of the years 1989-1992, those in Vienna in the years 1993-2001. RESULTS: We observed a change in the clinical pattern in our patients: patients from Bonn, who were diagnosed and treated about 5 years earlier, were more likely to suffer from melancholic depression, whereas Viennese patients rather suffered from atypical depression (chi(2) = 54.952, df = 2, p < 0.001). The symptoms of hypersomnia, daytime fatigue, increased eating and carbohydrate-craving were more frequent in the Viennese sample, anxiety and deterioration of patients' capacity to perform at work predominated in Bonn. In addition, patients from Vienna obtained a higher GSS (global seasonality score, measured by the SPAQ - Seasonal Pattern Assessment Questionnaire) than those from Bonn (15.7 +/- 3.3 and 14.6 +/- 4.1 respectively; t = 3.104, p = 0.002). Taken together, our results were in good accordance to other published SAD materials, but we were able to demonstrate that our patients reported "feeling worst" (measured by item 13H of the SPAQ) in November and December, whereas SAD patients in the USA clearly had their worst months in January and February. CONCLUSIONS: We suggest that an increase in awareness of fall-winter depression in the last decade by both doctors, who referred patients, as well as patients or the entire population must have caused patients to sign up for light therapy at the Viennese SAD clinic because of having heard about the atypical symptom profile. This increased awareness of SAD can also be measured by a statistically significant reduction in the diagnostic latency (from the age of onset to the diagnosis of SAD) when comparing the two study locations.

Adult↗
PubMed2002

Intravenous mirtazapine in the treatment of depressed inpatients.

Mirtazapine is a novel antidepressant with a noradrenergic and specific serotonergic mode of action. So far, mirtazapine has been administered orally. This naturalistic study evaluates the antidepressant efficacy, safety, and tolerability of mirtazapine 15 mg/day administered intravenously to 27 inpatients with moderate to severe major depression. Compared with baseline, we found a significant decrease of the Hamilton Depressive Rating Scale (HDRS) total score (P<0.001). Side effects were mild and transient. Altogether, the results of this preliminary study show that intravenous mirtazapine is an effective, safe and well tolerated treatment for depressed inpatients.

Adrenergic alpha-Antagonists↗
PubMed2001

Cross-reactive binding of cyclic peptides to an anti-TGFalpha antibody Fab fragment: an X-ray structural and thermodynamic analysis.

The monoclonal antibody tAb2 binds the N-terminal sequence of transforming growth factor alpha, VVSHFND. With the help of combinatorial peptide libraries it is possible to find homologous peptides that bind tAb2 with an affinity similar to that of the epitope. The conformational flexibility of short peptides can be constrained by cyclization in order to improve their affinity to the antibody and their stability towards proteolysis. Two cyclic peptides which are cross-reactive binders for tAb2 were selected earlier using combinatorial peptide libraries. One is cyclized by an amide bond between the N-alpha group and the side-chain of the last residue (cyclo-SHFNEYE), and the other by a disulfide bridge (cyclo-CSHFNDYC). The complex structures of tAb2 with the linear epitope peptide VVSHFND and with cyclo-SHFNEYE were determined by X-ray diffraction. Both peptides show a similar conformation and binding pattern in the complex. The linear peptide SHFNEYE does not bind tAb2, but cyclo-SHFNEYE is stabilized in a loop conformation suitable for binding. Hence the cyclization counteracts the exchange of aspartate in the epitope sequence to glutamate. Isothermal titration calorimetry was used to characterize the binding energetics of tAb2 with the two cyclic peptides and the epitope peptide. The binding reactions are enthalpically driven with an unfavorable entropic contribution under all measured conditions. The association reactions are characterized by negative DeltaC(p) changes and by the uptake of one proton per binding site. A putative candidate for proton uptake during binding is the histidine residue in each of the peptides. Hydrogen bonds and the putative formation of an electrostatic pair between the protonated histidine and a carboxy group may contribute markedly to the favorable enthalpy of complex formation. Implications to cyclization of peptides for stabilization are discussed.

Amino Acid Sequence↗
PubMed2001

Magnetic field dependence of the superconducting gap and the pseudogap in Bi2212 and HgBr2-Bi2212, studied by intrinsic tunneling spectroscopy.

Intrinsic tunneling spectroscopy in high magnetic field (H) is used for a direct test of superconducting features in the quasiparticle density of states of pure Bi2212 and intercalated HgBr2-Bi2212 high- T(c) superconductors. We were able to distinguish with great clarity two coexisting gaps: (i) the superconducting gap, which closes as H-->H(c2)(T), and (ii) the c-axis pseudogap, which does not change either with H or with T. Strikingly different H dependencies, together with previously observed different temperature dependencies of the two gaps, speak against a superconducting origin of the pseudogap.

Journal Article↗
PubMed2001

[Fusion of MRI, fMRI and intraoperative MRI data. Methods and clinical significance exemplified by neurosurgical interventions].

The aim of this work was to realize and clinically evaluate an image fusion platform for the integration of preoperative MRI and fMRI data into the intraoperative images of an interventional MRI system with a focus on neurosurgical procedures. A vertically open 0.5 T MRI scanner was equipped with a dedicated navigation system enabling the registration of additional imaging modalities (MRI, fMRI, CT) with the intraoperatively acquired data sets. These merged image data served as the basis for interventional planning and multimodal navigation. So far, the system has been used in 70 neurosurgical interventions (13 of which involved image data fusion--requiring 15 minutes extra time). The augmented navigation system is characterized by a higher frame rate and a higher image quality as compared to the system-integrated navigation based on continuously acquired (near) real time images. Patient movement and tissue shifts can be immediately detected by monitoring the morphological differences between both navigation scenes. The multimodal image fusion allowed a refined navigation planning especially for the resection of deeply seated brain lesions or pathologies close to eloquent areas. Augmented intraoperative orientation and instrument guidance improve the safety and accuracy of neurosurgical interventions.

Adult↗
PubMed2000

Evidence for coexistence of the superconducting gap and the pseudogap in Bi-2212 from intrinsic tunneling spectroscopy.

We present intrinsic tunneling spectroscopy measurements on small Bi2Sr2CaCu2O8+x mesas. The tunnel conductance curves show both sharp peaks at the superconducting gap voltage and broad humps representing the c-axis pseudogap. The superconducting gap vanishes at Tc, while the pseudogap exists both above and below Tc. Our observation implies that the superconducting and pseudogaps represent different coexisting phenomena.

Journal Article↗
PubMed2000

The ATM gene in the pathogenesis of mantle-cell lymphoma.

BACKGROUND: Mantle-cell lymphoma (MCL) is genetically characterized by the translocation t(11;14)(q13;q32) leading to an overexpression of cyclin-D1, but additional chromosomal abnormalities appear to be required for MCL pathogenesis. PATIENTS AND METHODS: Deletions involving chromosome 11q, which were recently found as recurrent aberrations in MCL, were analyzed at the molecular level in a series of 81 MCL by fluorescence in situ hybridization (FISH) with probes from a contiguous set of yeast artificial chromosomes (YACs) spanning bands 11q14-q24. RESULTS AND CONCLUSIONS: Loss of chromosome 11 material was observed in 37 of the 81 MCL cases (46%). The consensus deletion comprised YAC 801e11 containing the ATM gene. The minimal region of loss was further narrowed with P1-derived artificial chromosome (PAC) probes. This allowed the identification of a deletion confined to the genomic region of ATM, which, together with intragenic mutations found in the coding sequence, suggests a role of ATM as a tumor suppressor gene in MCL.

Ataxia Telangiectasia Mutated Proteins↗
PubMed1999

Molecular characterization of 11q deletions points to a pathogenic role of the ATM gene in mantle cell lymphoma.

Deletions involving the long arm of chromosome 11 (11q) have been recently found as recurrent chromosome aberrations in mantle cell lymphoma (MCL). In the current study, the incidence and molecular extent of 11q deletions were analyzed in a series of 81 MCL by fluorescence in situ hybridization with probes from a contiguous set of yeast artificial chromosomes (YACs). Loss of chromosome 11 material was observed in 37 of 81 cases (46%). The minimally deleted segment comprised YAC 801e11 containing the ATM gene. To further narrow the minimal region of loss, P1-derived artificial chromosomes mapping to the critical region were isolated and used as probes in cases without aberrations detectable with YACs. This allowed the identification of an ATM deletion that was beyond the resolution of YAC probes. The identification of a minimally deleted segment affecting ATM suggests a pathogenic role of ATM as a tumor suppressor gene in MCL.

Ataxia Telangiectasia Mutated Proteins↗
PubMed1999

Spinal markers: A new method for increasing accuracy in spinal navigation.

Spinal navigation opens up a completely new dimension in the planning and realization of neurosurgical and orthopedic procedures, and offers the possibility of simulating the operation preoperatively. There is currently only limited experience with spinal navigation, and despite the development of advanced software, intraoperative difficulties include identification of characteristic and reproducible anatomical landmarks, localization of these points in the surgical field, referencing, and intraoperative control. We report the use of a new kind of implantable fiducial marker in a case of a 58-year-old female patient with spondylolisthesis. Percutaneously applied spinal markers were used as prominent anatomical landmarks and permitted much easier intraoperative handling. In our opinion, in the hands of an experienced neurosurgeon or orthopedist, the additional preoperative time required for placement of such spinal markers is negligible.

Bone Nails↗
PubMed1999

The protective effect of iloprost, a PGL2 analogue, on ultratructure of ischemic and reperfused myocardial myocytes.

Iloprost was used in experiments with dogs to investigate its ultrastructure-preserving effects on the myocardium during ischemia and reperfusion, focussed especially on the mitochondria. Ischemia was performed by ligation of the left anterior descending coronary artery (LAD) for 90 min followed by reperfusion of 180 min. Samples were taken from the ischemic and non-ischemic area before ligation of LAD, immediately after ischemia and reperfusion. Iloprost was applicated into the left femoral vein after the end of LAD ligation. Ultrastructural-morphometric analysis revealed that iloprost was able to diminish damages of the mitochondria after ischemia and reperfusion as well. Mitochondrial oedema and intramitochondrial structure degenerations (destruction of cristae and matrix) were minimized in contrast to results of unprotected animals, which had to undergo the same procedure as indicated by volume, volume densities of mitochondria, and of the intramitochondrial compartments, confirmed by independent secondary morphometric parameters. There were no remarkable differences between the corresponding parameters of mitochondria in the ischemic and non-ischemic area.

Animals↗
PubMed1999

The protective effect of lipoxygenase inhibitor FLM 5011 on mitochondria ultrastructure of ischemic and reperfused cardiomyocytes.

Lipoxygenase inhibitor FLM 5011 was used in experimental ischemia and reperfusion with dogs to investigate its ultrastructure-preserving effects on the mitochondria of myocardium. Ischemic and non-ischemic areas of the heart were ultrastructural-morphometric analysed, which revealed that FLM 5011 was able to diminish ischemic damage especially of mitochondria. The protective effects on mitochondria consisted mainly in reduction of defective intramitochondrial areas and in excellent protection of the structural integrity of cristae and matrix. The injury of mitochondria by ischemia/reperfusion in unprotected condition was partly more pronounced in the non-ischemic than in the ischemic area of the hearts probably caused by compensatory overload of the residual myocardium.

Animals↗
PubMed1999

Spot synthesis: observations and optimizations.

Positionally addressable syntheses of peptides on continuous cellulose membranes (spot synthesis) have often been reported in detail, but important questions dealing with synthesis quality, reproducibility and subsequent binding assays have largely been under-emphasized. In this report we have investigated some of these problems. The most important results were: (i) the signal intensity of ligate binding to cellulose-bound peptides and the affinity of the corresponding soluble peptides show good correlation, illustrated by three different ligate binding assays; (ii) reducing peptide density on the cellulose avoids the 'ring spot' effect, i.e. where less binding is observed in the spot-center compared to the rim. We recommend a peptide density of 10 nmol/cm2 as a reasonable starting point for further optimization; (iii) statistical analysis of binding assay reproducibility with more than 15000 peptides resulted in a mean standard signal deviation of 0.18; and (iv) optimization of side-chain deprotection revealed that a 30-min pretreatment of the cellulose with 90% trifluoroacetic acid followed by the standard deprotection protocol resulted in higher purity of the synthesized products.

Amino Acid Sequence↗
PubMed1998

Enkephalin analogs containing 4,4-difluoro-2-aminobutyric acid: synthesis and fluorine effect on the biological activity.

Analogs of Met-enkephalin and [D-Pen2, D-Pen5]enkephalin (DPDPE) containing the partially fluorinated amino acid 4,4-difluoro-2-aminobutyric acid (DFAB) in the 2- or 3-position of the peptide sequence were synthesized and their opioid activities and receptor selectivities were determined in vitro. The linear fluorinated [D-DFAB2, Met5-NH2]enkephalin showed mu and delta agonist potencies comparable to those of natural [Leu5]enkephalin. The partially fluorinated DPDPE analogs behaved differently as compared with their non-fluorinated correlates. While L-amino acid substitution in position 3 of DPDPE usually resulted in higher delta agonist potency than D-amino acid substitution. [D-DFAB3]DPDPE turned out to be a more potent delta agonist than [L-DFAB3]DPDPE. Furthermore, [D-DFAB3]DPDPE showed over 100-fold higher delta agonist potency than [D-Abu3]DPDPE (Abu = 2-aminobutyric acid), indicating that the fluorine substituents interact favorably with a delta opioid receptor subsite.

Aminobutyrates↗