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Biomedical subjects

S Winkler

Publications and source records attributed to S Winkler.

At least 55 records · Page 3Linked to original sources

Intraoperative fluorescence visualization of the parathyroid gland in rats.

Bilateral neck exploration is the standard procedure of primary hyperparathyroidism. Preoperative localization is not mandatory. Intraoperative visualization methods help to avoid unsuccessful explorations and to reduce morbidity rates. In our study, the application of 5-Aminolevulinic acid (5-ALA), a precursor in the heme biosynthesis pathway, led to Protoporphyrin IX (PpIX) accumulation within the parathyroid gland (PTG). PpIX, a metabolite of 5-ALA, causes red fluorescence (635 nm) when stimulated by light of a defined wavelength. Largely invisible under conventional illumination, all PTGs were fluorescence positive and detectable after PpIX targeting and blue light excitation (380-440 nm). Point spectrometry to measure fluorescence intensities, showed a fluorescence ratio between PTG and surrounding thyroid gland tissue of 5.7:1 (p < 0.001). Fluorescence guided PTG biopsies showed no false positive findings in histology. 5-ALA induced PpIX fluorescence to detect PTGs suggests to be a highly sensitive intraoperative visualization method. Hence, the performance of minimally invasive video-assisted parathyroidectomy will be facilitated by this innovative technique.

Aminolevulinic Acid↗

Medaka eyeless is the key factor linking retinal determination and eye growth.

The complete absence of eyes in the medaka fish mutation eyeless is the result of defective optic vesicle evagination. We show that the eyeless mutation is caused by an intronic insertion in the Rx3 homeobox gene resulting in a transcriptional repression of the locus that is rescued by injection of plasmid DNA containing the wild-type locus. Functional analysis reveals that Six3- and Pax6- dependent retina determination does not require Rx3. However, gain- and loss-of-function phenotypes show that Rx3 is indispensable to initiate optic vesicle evagination and to control vesicle proliferation, by that regulating organ size. Thus, Rx3 acts at a key position coupling the determination with subsequent morphogenesis and differentiation of the developing eye.

Amino Acid Sequence↗

The effect of implant diameter, restoration design, and occlusal table variations on screw loosening of posterior single-tooth implant restorations.

The purpose of this study was to (1) determine in vitro the effect of narrowing the buccolingual width of the occlusal table on the untightening torque required to loosen gold prosthetic screws after subjecting implants and implant-supported restorations to occlusal loads, and (2) to compare the incidence of screw loosening and values of untightening torque of the screws among crowns supported by 1 wide-diameter as opposed to 2 standard implants after loading in vitro. The restorations were divided into 4 groups (group 1, a narrow crown supported by one 5-mm wide-diameter implant; group 2, a narrow crown supported by 2 standard 3.75-mm-diameter implants; group 3, a wide crown supported by one 5-mm wide-diameter implant; and group 4, a wide crown supported by 2 standard 3.75-mm-diameter implants). A custom-designed chewing machine was used to simulate the grinding phase of the masticatory cycle and lateral excursions. The crowns were subjected to a 6-kg load for 16660 cycles over 5.5 hours and were loaded at the outer and inner inclines and cusp tips with an untightening loading pattern. The untightening torque was measured for the gold screws in the different groups before and after loading at 4 different locations for 8 cycles on the simulated chewing machine. A 1-way analysis of variance indicated a significant difference (P < .001) among the test groups. Pairwise multiple comparison tests (Scheffe) were carried out on mean "change scores." Group 3 was significantly different from the other groups, which were not significantly different from each other. Restoring missing molars with 1 wide-diameter implant had a greater incidence of screw loosening as compared with 2 implants. Narrowing the occlusal table of the restoration is critical when using 1 implant to support a missing molar. The untightening torque of gold screws was not affected by changing the width of the occlusal table of crowns supported by 2 implants.

Analysis of Variance↗

An overview of the Lew attachment: clinical reports.

Although the Lew attachment was originally developed to provide retention for overdentures fabricated in conjunction with subperiosteal implants, these attachments can also be used with other types of implants. Two cases are presented to describe the use of Lew attachments, one with a conventional subperiosteal implant, and the other with 4 endosteal implants and an implant connecting bar.

Adult↗

A new implant designed to maximize contact with trabecular bone: survival to 18 months.

PROBLEM: A roughened, commercially pure titanium (CP-Ti) implant design has been developed that features a different length and pitch for each screw thread to direct functional stresses away from cortical bone and to the more resilient trabecular bone. Abutment-implant connection is made using a conical taper to provide a seal against invasion by microorganisms. PURPOSE: To assess short-term (18 months) clinical performance of this innovative implant design. METHODS: A total of 1,419 implants were placed in 313 patients to support 419 prostheses in a multidisciplinary, multicentered, prospective clinical study conducted by the Ankylos Implant Clinical Research Group (AICRG). More than 100 dentists at 32 centers in the United States, 1 in Korea, and 1 in Taiwan are involved in the study. Failure was defined as implant removal for any reason. The influence of mobility at placement, implant length and diameter, incision type, augmentation, crestal bone reduction, bone density, and the use of the operating room or dental clinic on survival were evaluated over 18 months. Crestal bone loss between placement and uncovering was also determined. RESULTS: Crestal bone loss ranged from 0.2 to 0.5 mm. The overall success rate from placement to 18 months was 96.6%. Implants mobile at placement failed more frequently (16.9%) compared with stable implants (3.1%). Wide-diameter implants and longer implants exhibited higher survival rates. Incision design and surgery location did not influence survival. Bone density was important to clinical survival.

Adult↗

A 48-month multicentric clinical investigation: implant design and survival.

This report is based on a total of 2,955 implants of 6 different designs, randomized and placed in 829 patients and followed for 48 months. Implant failure was defined as nonintegration at uncovering or removal due to mobility, persistent pain, infection, and evidence of radiographic bone loss. Failures were reported for 3 phases of treatment: implant placement to uncovering (phase 1), uncovering to loading (phase 2), and postloading (phase 3). Differences in survival were compared with Kaplan-Meier survival curves. The maxillary single tooth application resulted in 95.2% survival for the hydroxyapatite-coated grooved implants. In the maxillary completely edentulous application, survival of hydroxyapatite grooved and screw implants were considerably better compared with the titanium screw implants. The hydroxyapatite-coated cylinder had better survival than the titanium basket and screw designs in the mandibular completely edentulous application. The hydroxyapatite-coated cylinder and grooved implants in the maxillary posterior partially edentulous application had similar survival rates. The survival of the hydroxyapatite-coated cylinder exceeded that of the titanium basket in mandibular posterior partially edentulous applications. Analyses by phase of treatment indicated a pattern of early failure for nonhydroxyapatite-coated implants compared with hydroxyapatite-coated implants. The implant with the highest survival at all phases of treatment was the hydroxyapatite-coated press-fit cylinder. Two hydroxyapatite-coated implant designs performed well in the challenging posterior maxillary region.

Adult↗

Stability of implants and natural teeth as determined by the Periotest over 60 months of function.

Various methods for evaluating tooth mobility have been developed throughout the years, but their acceptance has been limited because of the subjectivity associated with their use. In recent years, the Periotest has been studied and used to evaluate the mobility of natural teeth and is claimed to b e potentially reliable in assessing the stability of the implant-bone interface. Few clinical implant studies have used natural teeth as controls to monitor changes in mobility associated with dental implants. The Dental Implant Clinical Research Group initiated a long-term clinical study in 1991 to assess the influence of design, application, and site of placement on clinical success and crestal bone height. As part of the study, Periotest values (PTVs) were recorded for 2,623 of the 2,998 implants placed and uncovered. For the statistical analysis, 2,623 implants were tested at second-stage surgery, with the number of implants tested varying at each follow-up visit. Data were collected from investigators at 32 study centers for periods ranging up to 60 months. A total of 975 natural teeth from 409 partially edentulous study subjects served as controls. FPVs on natural teeth and implants were combined, and the overall average Periotest values (OA-PTVs) were compared with values for individual subjects. The effect of implant and natural tooth locations on mobility were evaluated and compared with each other. The combined OA-PTV for all natural teeth was +1.8 and the OA-PTV for all implants was -3.4 PTVs. Compared with those in the maxillae, mandibular teeth and implants were found to be more stable Implants were found to be significantly more stable as compared with natural teeth. The recorded variations in PTVs for natural teeth and implants over the entire evaluation period were not found to be significantly different. This study developed the following conclusions: (1) implants were found to be significantly less mobile as compared with natural teeth for individual subjects; (2) the PTVs for natural teeth and implants did not exhibit significant variation over the evaluation period; (3) the Periotest can provide reproducible assessment of stability in a long-term clinical study; and (4) changes in PTVs may be helpful in evaluating improvement or degradation of the implant-bone complex.

Dental Implantation, Endosseous↗

African-European differences in the capacity of T-cell cytokine production.

Regional differences in immune responsiveness have been studied by comparing the frequency of cytokine producing T cells in healthy African children and adults and their age-matched European counterparts. By use of flow cytometry for the intracellular detection of cytokines an overall expansion of CD4+ and CD8+ T cells producing the Type 1 cytokines interleukin (IL)-2 and interferon (IFN)-gamma was observed in adults when compared with children, giving credit to the cumulative effect of contacts with environmental antigens. The CD4+ cells expressing the Type 2 cytokines IL-4 and IL-13, however, increased only in Africans, probably reflecting continuously present challenges with antigens that preferentially drive Type 2 responses. A striking increased frequency of both Type 1 and Type 2 cytokines producing T cells was found in African adults when compared with their European counterparts. The quantitative and qualitative regional differences in immune reactivity are likely to be of significance for all immune intervention strategies, especially for the design of vaccines.

Adult↗

A new approach towards modelling of the carbon degradation cycle at two-stage activated sludge plants.

A pilot plant has been operated in order to investigate the performance and operating characteristics of the plant concept developed for the extension of the main Vienna STP. Due to the different operational modes included in the plant concept, modelling of the carbon degradation becomes of crucial importance. A new activated sludge model is introduced which combines parts of the carbon degradation model concepts as they have been released in the ASM1-model and the ASM3-model, respectively. A method is presented which utilises results from mass balance calculations and sludge stabilisation experiments to reduce the uncertainty in the determination of the values of the simulation model parameters.

Aerobiosis↗

Comparison of different operational modes of a two-stage activated sludge pilot plant for the extension of the Vienna STP.

A pilot plant has been operated over a period of two years in order to investigate the performance and the operating characteristics of the plant concept developed for the extension of the main Vienna STP and to develop a simulation model which will be applied for operation support of the full stage plant. The pilot plant is a two stage activated sludge plant, each stage comprising of four aeration tanks and a clarifier tank. The pilot plant layout allows three different operational modes, each of which has been operated for several periods. The performance of the pilot plant during these periods is described and the different operational modes are compared to each other.

Equipment Design↗

A new process for integrated treatment of industrial wastewater at municipal wastewater treatment plants.

A new process for integrated treatment of industrial wastewater at a municipal WWTP is presented. The process uses the ability of heterotrophic bacteria of rapid substrate uptake and storage. The excess sludge from the municipal treatment line is fed to a contact tank, which receives the industrial wastewater via a separate pipeline. The contact tank is aerated to such a degree that secures complete substrate uptake but minimises oxygen consumption due to instant substrate degradation. The sludge from the contact tank is mechanically pre-thickened and then fed to an anaerobic digester. Hence, the major portion of the incoming COD load of the industrial wastewater is transferred to the anaerobic digester, where it contributes to an increased biogas production. The back load of the industrial wastewater treatment process to the municipal treatment line is very low.

Austria↗

Controlling beta-sheet assembly in genetically engineered silk by enzymatic phosphorylation/dephosphorylation.

Enzymatic phosphorylation and dephosphorylation reactions were used to modify a genetically engineered variant of spider dragline silk. The approximately 25 kDa protein was phosphorylated with cyclic AMP-dependent kinase and dephosphorylated with calf intestinal alkaline phosphatase. Phosphorylation inhibited beta-sheet assembly of the protein and enhanced solubility to about 5 mg/mL in water, compared to about 20% of this level upon enzymatic dephosphorylation. The cyclability of the phosphorylation-dephosphorylation system was confirmed by MALDI with a model peptide. Kinetic studies conducted with [gamma-(32)P]ATP illustrate that the phosphorylation reaction proceeds over 6 h. Secondary structure of the phosphorylated and dephosphorylated proteins was determined by CD and FTIR. The results illustrate that an enzymatic phosphorylation event can be used to control the solution structure of a protein like silk, which has a tendency to prematurely precipitate due to the formation of beta-sheets.

Amino Acid Sequence↗

Metabolization of beta-(2,6)-linked fructose-oligosaccharides by different bifidobacteria.

Low-molecular-mass beta-(2,6)-linked fructose-oligosaccharides (beta-(2,6)-FOS) were examined as a new carbohydrate source for growth of bifidobacteria. beta-(2,6)-FOS were prepared from microbial high-molecular-mass levan by acid hydrolysis and refined by cation-exchange chromatography. (13)C-NMR spectroscopy confirmed the presence of predominantly beta-(2,6)-fructosyl linkages in the oligosaccharides. More than 80% beta-(2,6)-FOS was recovered after in vitro incubation with amylolytic and proteolytic enzymes, implying resistance to degradation in the upper intestinal tract. Bifidobacterium adolescentis, B. longum, B. breve, and B. pseudocatenulatum were studied in vitro for their ability to metabolize beta-(2,6)-FOS. Growth, decrease in pH, formation of short- chain fatty acids (lactate, acetate, formate) and degradation of beta-(2,6)-FOS were markedly different among species. B. adolescentis showed the best growth, produced the highest amounts of organic acids and metabolized both short- and long-chain beta-(2, 6)-FOS.

Bifidobacterium↗

Chlorpromazine induces apoptosis in activated human lymphoblasts: a mechanism supporting the induction of drug-induced lupus erythematosus?

OBJECTIVE: Drug-induced lupus erythematosus is a serious side effect of certain medications, such as procainamide, quinidine, hydralazine, chlorpromazine, and isoniazid, the underlying pathogenesis of which is unresolved. In this study, we examined the influence of these drugs on the regulation of apoptosis, or programmed cell death, in quiescent and activated human lymphocytes. We also discuss the dysregulation of apoptosis as a pathogenetic factor in systemic lupus erythematosus. METHODS: Peripheral blood mononuclear cells or activated lymphoblasts from normal donors were incubated with different concentrations of each of the above-mentioned drugs. RESULTS: We did not find induction of apoptosis in quiescent cells over a broad concentration range. In contrast, lymphoblasts readily underwent apoptosis when cultured with chlorpromazine, but not any of the other drugs, after stimulation with interleukin-2 (IL-2) in a dose-, time- and cell cycle-dependent manner. By several lines of evidence, toxicity was ruled out. Characteristic features of apoptosis-like incorporation of propidium iodide (PI), such as increased annexin V binding, changes in mitochondrial membrane potential, and induction of DNA breaks (as evidenced by TUNEL techniques), could be induced in lymphoblasts after chlorpromazine treatment. Chlorpromazine did not cause apoptosis by inhibition of cytokine binding or blockade of early intracellular signaling. The protease inhibitor Z-VAD and the ceramide inhibitor sphingosine 1-phosphate effectively blocked chlorpromazine-induced apoptosis (by PI staining and by externalization of phosphatidylserine), in contrast to the caspase 3/CPP32 inhibitor DEVD, which had only minor effects. Western blot analysis revealed IL-2-mediated phosphorylation of extracellular signal-regulated kinase, which was sensitive to chlorpromazine. Using lymphoblasts from a patient with Canale-Smith syndrome, we found that chlorpromazine-mediated apoptosis is Fas/ APO-1 independent. CONCLUSION: These data suggest that chlorpromazine mediates apoptosis in human lymphoblasts through specific activation of intracellular proapoptotic signaling cascades. This mechanism might lead to an unsynchronized inflow of apoptotic break-down products and thereby to the induction of (auto)immunity against nuclear components.

Apoptosis↗

Experiences with severe P. falciparum malaria in the intensive care unit.

OBJECTIVE: To review the clinical profiles and therapies instituted for patients with severe malaria admitted to an ICU. DESIGN: Retrospective study. SETTING: Internal ICU of a tertiary care centre. PATIENTS AND PARTICIPANTS: Between January, 1992, and February, 1999, 104 patients with malaria were admitted to the General Hospital of Vienna. Sixty-nine patients suffered from Plasmodium falciparum malaria (66%), seven of these were admitted to the ICU. MEASUREMENT AND RESULTS: Seven patients were admitted to the ICU, of whom three died (4% in hospital case-fatality rate). Four patients required mechanical ventilation because of respiratory insufficiency and adult respiratory distress syndrome (ARDS), of whom three died. Three patients were treated with inhaled nitric oxide (NO) and kinetic therapy; one patient required extracorporeal veno-venous oxygenation. All patients who died required haemofiltration because of acute renal failure. CONCLUSION: As P. falciparum is a potentially life-threatening disease, reliable criteria for ICU admission should be defined and risk factors identified. Early ICU monitoring should be attempted, especially under the following conditions: (1) lack of clinical response to anti-malarial treatment within 48 h and/or (2) any signs of neurological disturbance (hypoglycaemia excluded). Prospective multicentre trials and guidelines for supportive intensive care are urgently needed.

Adult↗

Establishment of a novel in vitro system for studying the interaction of xenobiotic metabolism of liver and intestinal microflora.

We developed a new two-chamber system for the coculture of hepatocytes and fecal microflora under aerobic and anaerobic conditions, respectively, to investigate the sequential metabolism of chemicals by the liver and microflora in vitro. The culture device consisted of two chambers separated by a permeable polycarbonate membrane. In the aerobic compartment, hepatocytes were cultivated as a monolayer on the membrane and in the anaerobic compartment fecal microflora as a suspension. To characterize the metabolic capacity of the microflora and hepatocytes, various marker enzymes were studied. Azoreductase, nitroductase, beta-glucuronidase, beta-glucosidase and sulphatase were tested in the microflora of the feces from three volunteers who had had significantly different eating habits for years (daily meat, mixed diet, vegetarian). The microflora exhibited significant activities and the various enzymes differed only moderately in the samples from the three volunteers. For rat hepatocytes the activities of various cytochrome P450 forms and conjugating enzymes served as markers. The enzyme activities were tested in the coculture system during a 4-h culture period intended for the test protocol. Deethylation of ethoxycoumarin and 2alpha-, 6beta- and 16alpha-hydroxylation of testosterone decreased by about 30%, 25%, 40% and 20%, respectively, while there was no loss of glucuronidation and sulphonation of 3-OH-benzo(a)pyrene nor of glutathione conjugation of 1-chloro-2,4-dinitrobenzene during the 4-h culture period. The activities of the tested hepatic phase I and II enzymes were not changed after coculture of the hepatocytes with the microflora for 4 h. The applicability of the in vitro system for studying the metabolic interaction of liver and microflora was demonstrated using 7-ethoxycoumarin and the developmental drug EMD 57033, a thiadiazinon derivative from Merck KGaA, as model compounds. Both compounds were oxidized and conjugated by liver cells. In the coculture of hepatocytes and fecal microflora the resulting glucuronides and sulphoconjugates were split by hydrolytic enzymes of the intestinal microflora.

Adult↗

Molecular biology of spider silk.

Spider silks are an intriguing family of fibrous proteins due to their highly repetitive primary sequence, their solution properties and their assembly and processing into fibers with remarkable mechanical properties. Current research efforts aimed at understanding and manipulating genes encoding these proteins are helping to gain insight into the relationships between protein sequence, protein assembly and macromolecular properties.

Animals↗