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Biomedical subjects

M Schuster

Publications and source records attributed to M Schuster.

At least 19 recordsLinked to original sources

Indications for acceleration-dependent changes of membrane potential in the flagellate Euglena gracilis.

The effects of the calcium sequester EGTA on gravitactic orientation and membrane potential changes in the unicellular flagellate Euglena gracilis were investigated during a recent parabolic-flight experiment aboard of an Airbus A300. In the course of a flight parabola, an acceleration profile is achieved which yields subsequently about 20 s of hypergravity (1.8 g(n)), about 20 s of microgravity, and another 20 s of hypergravity phases. The movement behavior of the cells was investigated with real-time, computer-based image analysis. Membrane potential changes were detected with a newly developed photometer which measures absorption changes of the membrane potential-sensitive probe oxonol VI. To test whether the data obtained by the oxonol device were reliable, the signal of non-oxonol-labelled cells was recorded. In these samples, no absorption shift was detected. Changes of the oxonol VI signals indicate that the cells depolarize during acceleration (very obvious in the step from microgravity to hypergravity) and slightly hyperpolarize in microgravity, which can possibly be explained with the action of Ca-ATPases. These signals (mainly the depolarization) were significantly suppressed in the presence of EGTA (5 mM). Gravitaxis in parallel was also inhibited after addition of EGTA. Initially, negative gravitaxis was inverted into a positive one. Later, gravitaxis was almost undetectable.

Acceleration↗

Ensembl 2007.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of chordate genome sequences. Over the past year the number of genomes available from Ensembl has increased from 15 to 33, with the addition of sites for the mammalian genomes of elephant, rabbit, armadillo, tenrec, platypus, pig, cat, bush baby, common shrew, microbat and european hedgehog; the fish genomes of stickleback and medaka and the second example of the genomes of the sea squirt (Ciona savignyi) and the mosquito (Aedes aegypti). Some of the major features added during the year include the first complete gene sets for genomes with low-sequence coverage, the introduction of new strain variation data and the introduction of new orthology/paralog annotations based on gene trees.

Animals↗

Peptide arrays for the determination of humoral responses induced by active immunization with a monoclonal antibody against EpCAM.

Epithelial cell adhesion molecule (EpCAM) is an attractive target for monoclonal antibody serotherapy because it is over-expressed in approximately 70% of epithelial cancers and their metastatic lesions. IGN101, the immunogenic formulation of the murine monoclonal anti-EpCAM antibody Mab17-1A, has been shown to evoke a strong humoral immune response in both monkey studies and early clinical trials. Notably, there was a reduction in the number of circulating EpCAM-positive tumor cells in the peripheral blood of treated cancer patients. In contrast to earlier publications by other groups, we could not detect an anti-EpCAM immune response upon treatment with Mab17-1A using a conventional but optimized anti-EpCAM ELISA. Therefore, in a novel experimental setup, sera of healthy immunized monkeys, normal human donors and cancer patients immunized with IGN101 were tested for reactivity against a series of overlapping synthetic peptides encompassing the entire sequence of EpCAM prepared by SPOT synthesis on cellular supports. Using this method, sera from normal donors reacted with different peptides compared to sera from healthy monkeys. However, the peptides were clustered in the same regions of EpCAM. Cancer patients generally had a lower reactivity to EpCAM peptides and immunization with IGN101 induced reactivity against a different set of peptides. Antibodies cross-reacting with both the IgG2a framework and with the Mab17-1A idiotype were identified. In summary, our data indicate that some EpCAM peptides may be recognized in a species-specific manner. At least seven EpCAM-derived peptides could be of diagnostic interest (QCQCTSVGAQ, ERVRTYWIII, ALQKEITTRY, TYWIIIELKH, IADVAYYFEK, AYYFEKDVKG, GQTLIYYVDE), while four out of these seven peptides may also possess therapeutic relevance (TYWIIIELKH, ALQKEITTRY, IADVAYYFEK, AYYFEKDVKG).

Amino Acid Sequence↗

Observation of soliton fusion in a Josephson array.

The behavior of topological solitons in a parallel array of a Josephson junction is studied experimentally. We observe the fusion of two relativistic solitons of the same polarity into a single soliton. The soliton carries two quanta of magnetic flux and, most strikingly, travels 18% faster than an ordinary soliton under the same driving force. We also find a variety of bunched states composed of solitons of the same polarity, moving with fixed separation.

Journal Article↗

Ensembl 2006.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of large genome sequences. Over the last year the number of genomes available from the Ensembl site has increased from 4 to 19, with the addition of the mammalian genomes of Rhesus macaque and Opossum, the chordate genome of Ciona intestinalis and the import and integration of the yeast genome. The year has also seen extensive improvements to both data analysis and presentation, with the introduction of a redesigned website, the addition of RNA gene and regulatory annotation and substantial improvements to the integration of human genome variation data.

Animals↗

[The use of diagnosis-related-groups data for external benchmarking of anesthesia and intensive care services].

Measurement and assessment of the economic efficiency of clinical departments is still an unresolved, yet important problem in hospital management. Benchmarking with other providers can help to evaluate one's own efficacy in anaesthesia and intensive care services. In this article we describe a method for using the diagnosis-related-groups (DRG) cost breakdown data, to achieve a case mix adjusted comparison of own costs for anaesthesia and intensive care services with the average costs in German hospitals. On the basis of 19,401 cases from 10 different surgical departments, we compared our own costs with the German-wide benchmark. Major factors for profit optimisation are discussed. Special attention is given to the close interaction of surgical, anaesthesiological and intensive care process performance and costs and its impact on benchmarking studies.

Anesthesia↗

[Hearing impairment in children and adolescents with Down's syndrome].

BACKGROUND: There are controversial opinions about the incidence of hearing impairment of children and adolescents with Down's syndrome as an additional cause for obstruction in social and communicative live. Next to congenital diseases of the inner ear, functional limitations can often lead to conductive hearing disorders in patients with Down's syndrome. PATIENTS AND METHODS: The hearing ability, otoscopic and audiometric characteristics of 115 patients aged 3.2+/-2.9 years were analysed retrospectively over 42 months. RESULTS: A total of 86 children showed morphologic otoscopic peculiarities: transitory evoked otoacoustic emissions (TEOAE) were often non-reproducible, even in patients with normal hearing abilities(14.1% of cases), and were not evaluable in 32.8% of cases. Half of the patients showed hearing loss, 82% of whom suffered from a conductive hearing loss, 6.9% from a combined, and 8.6% from isolated sensorineural hearing loss. Hearing loss was first diagnosed when the children were 4.6+/-3.4 years old. CONCLUSION: The frequent occurrence of hearing loss justifies and requires an early and continuous pedaudiological examination. As a common screening examination, TEOAE is limited due to its cost, however, it fulfils its purpose as a means of distinguishing healthy children from those with possible hearing disorders. In most cases, objective and subjective audiometric methods must be combined in order to precisely define the hearing ability.

Adolescent↗

[Prosthetic voice rehabilitation after laryngectomy. Failures and complications after previous radiation therapy].

BACKGROUND: Indwelling voice prostheses are state of the art for post-laryngectomy voice rehabilitation. The aim of this study was to identify the impact of radiation prior to tracheoesophageal puncture on success rate and complications. PATIENTS AND METHODS: We undertook a retrospective study of 145 patients who had undergone prosthetic voice restoration between 1990 and 2002 (Provox) and Provox2). Risks of functional failure and complications in 17 patients with previous radiation therapy were compared to those of 128 patients without such therapy. RESULTS: Previous radiation increased not only the risk of functional failure by 2.9 (P=0.023), but also the risk of shunt-related complications such as aspiration around the prosthesis (1.51; P=0.046), widening of the shunt (2.32; P=0.014), esophageal (2.51; P=0.013) or tracheal (3.29; P=0.0023) dislocation of the prosthesis and spontaneous (2.51; P=0.047) or surgical closure (3.76; P=0.037) of the shunt. CONCLUSION: Primary tracheoesophageal puncture during laryngectomy is recommended in cases without previous radiation therapy, especially when post-laryngectomy radiation is likely. In patients with previous radiation therapy, generally good success rates decrease, however, without absolute contraindication of tracheoesophageal puncture. These results may affect salvage surgery concepts.

Adult↗

Pulmonary embolism caused by polymethylmethacrylate during percutaneous vertebroplasty in orthopaedic surgery.

Vertebroplasty consists of percutaneous injection of acrylic cement--polymethylmethacrylate (PMMA)--into a partially collapsed vertebral body in order to obtain pain relief and augment mechanical stability of the vertebral body. Although vertebroplasty is an efficient treatment it is not free of complications. Our present case report describes a woman with pulmonary polymethylmethacrylate embolism during percutaneous vertebroplasty who presented with hypotension, arrhythmia and hypocapnia.

Anticoagulants↗

Invasive fungal infections in low-risk liver transplant recipients: a multi-center prospective observational study.

Prevention of invasive fungal infections (IFIs) in orthotopic liver transplant (OLT) recipients utilizing postoperative systemic antifungal prophylaxis, typically with fluconazole, is justified among those at high risk for IFI. Use of postoperative antifungal prophylaxis for low-risk OLT recipients is widely practiced but not universally accepted nor supported by data. We conducted a prospective observational study among 200 OLT recipients who were at low risk for IFI and did not receive postoperative antifungal prophylaxis. Patients were considered low risk if they had </=1 of the following conditions: choledochojejunostomy anastomosis; retransplantation; intra-operative administration of >/=units of 40 blood products or return to the operating room for intra-abdominal bleeding; return to the operating room for anastomotic leak or vascular insufficiency; preoperative serum creatinine of >/=2 mg/dL; and perioperative Candida colonization. Patients were followed 100 d post-transplantation for evidence of IFI. Of 193 eligible patients, 7 (4%) developed an IFI. Three (2%) IFIs were due to Candida spp. and potentially preventable by standard fluconazole prophylaxis. Three patients developed invasive aspergillosis; one developed late onset disseminated cryptococcosis. Liver transplant recipients at low risk for IFI can be identified utilizing pre-determined criteria, and post-transplantation antifungal prophylaxis can be routinely withheld in these patients.

Adult↗

Posaconazole as salvage therapy for zygomycosis.

Zygomycosis, an infection that is associated with significant morbidity and mortality, is becoming common in immunocompromised patients. Posaconazole is a new extended-spectrum azole antifungal that has demonstrated in vitro and in vivo activity against zygomycetes. This report provides the results from the first 24 patients with active zygomycosis who were enrolled in two open-label, nonrandomized, multicentered compassionate trials that evaluated oral posaconazole as salvage therapy for invasive fungal infections. Posaconazole was usually given as an oral suspension of 200 mg four times a day or 400 mg twice a day. Eleven (46%) of the infections were rhinocerebral. Duration of posaconazole therapy ranged from 8 to 1,004 days (mean, 292 days; median, 182 days). Rates of successful treatment (complete cure and partial response) were 79% in 19 subjects with zygomycosis refractory to standard therapy and 80% in 5 subjects with intolerance to standard therapy. Overall, 19 of 24 subjects (79%) survived infection. Survival was also associated with surgical resection of affected tissue and stabilization or improvement of the subjects' underlying illnesses. Failures either had worsening of underlying illnesses or requested all therapy withdrawn; none of the failures received more than 31 days of posaconazole. Posaconazole oral solution was well tolerated and was discontinued in only one subject due to a drug rash. Posaconazole appears promising as an oral therapy for zygomycosis in patients who receive required surgery and control their underlying illness.

Administration, Oral↗

Ensembl 2005.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of large genome sequences. Over the last year the number of genomes available from the Ensembl site has increased by 7 to 16, with the addition of the six vertebrate genomes of chimpanzee, dog, cow, chicken, tetraodon and frog and the insect genome of honeybee. The majority have been annotated automatically using the Ensembl gene build system, showing its flexibility to reliably annotate a wide variety of genomes. With the increased number of vertebrate genomes, the comparative analysis provided to users has been greatly improved, with new website interfaces allowing annotation of different genomes to be directly compared. The Ensembl software system is being increasingly widely reused in different projects showing the benefits of a completely open approach to software development and distribution.

Animals↗

[Therapy for unilateral vocal fold palsy].

The main symptom of unilateral vocal fold palsy is hoarseness, which can cause considerable disturbance to the patient depending on its extent and the patient's individual situation. Therapy aims at the restitution of a tuneful and resilient voice, which can be achieved by surgical or conservative means, improving the glottal closure and synchronizing the vocal fold vibrations during phonation. Vocal therapy is a common conservative method that may be supported by psychotherapeutic or physical procedures. In surgical therapy, there is a distinction between techniques of endoscopic augmentation by injecting different materials into the vocal folds and transcutaneous laryngeal framework surgery, i.e., transferring the paralyzed vocal fold to the glottal midline. Particularly apt for injection are biocompatible materials amount and position whose can easily be controlled. However, the inevitable resorption of many materials causes deterioration in voice quality. Furthermore, the change of vocal fold morphology obstructs regular phonatory vibration. On the other hand, medialization thyroplasty leads to permanent voice amelioration without a substantial complication rate when performed by experienced surgeons.

Hoarseness↗

Safety of gold in stapes surgery.

Gold prostheses in middle ear surgery were found to have a higher extrusion rate than prostheses made from titanium. Incidences of deafness after insertion of a gold piston into the vestibule during stapes surgery have been observed. The aim of this study was to find out to what degree gold cations can diffuse from the prosthesis piston into the perilymph. For this, gold prostheses were incubated in artificial perilymph for four months, after which the gold content of the perilymph was analysed. As gold exhibits a special behaviour in complex fluids like the perilymph, a new analysing method was developed. The results show that gold does leak out of the pistons, that it can be reliably measured and that the amount of gold reaching the perilymph depends on the contact area. As the amount of gold measured in the perilymph stays far below the toxic level, it is very unlikely that the gold cations diffusing from a stapes prosthesis into the perilymph have a toxic effect on the inner ear hair cells. Inflammatory or allergic reactions to gold induced by direct tissue contact, however, cannot be excluded.

Animals↗

[Quality of life and voice handicap of laryngectomees using tracheoesophageal substitute voice].

BACKGROUND: Health-related quality of life (QoL) and subjective health have become popular constructs for the evaluation of both efficacy and efficiency of diagnostic and therapeutic procedures in medicine. QoL is considered a multidimensional construct encompassing physical, mental and social facets of life. It is an accepted outcome parameter not only in international classification systems such as ICIDH and ICF, but as well in clinical guidelines and disease management programs. Measuring quality of life allows for comparison of different diseases though it certainly lacks disease specific aspects. Thus, it has to be assumed that in patients with distinct functional deficits QoL cannot cover all aspects that are important for the individual patient. This study focuses on laryngectomies and their self-evaluation of post-laryngectomy speech. It is well known that these patients experience a decreased QoL compared to patients after partial laryngectomy or healthy persons. In this study, the impact of voice restoration on the laryngectomies' QoL was evaluated. PATIENTS AND METHODS: In 20 male laryngectomies aged 62 +/- 8 years, relations between QoL and voice handicap were evaluated using two instruments as proposed in the international literature, i. e. the Short-Form Health Survey (SF-36) and the Voice Handicap Index (VHI). All patients had successfully been using tracheoesophageal substitute voice for at least one year. Complete data sets were available from all patients. Data were analysed using Microsoft Excel and Sigma Plot, Jandel Corp. software packages. RESULTS: Results of both the SF-36 and the VHI reveal wide interindividual ranges. There are statistically significant correlations (p < 0.05) between the SF-36's scales General Health and Vitality and the VHI, whereas no correlations were found between social and psychological scales and the voice handicap. DISCUSSION: Wide ranges of the data obtained reveal that obviously both health related quality of life and voice handicap are not affected in a group specific way. So, both tests are of clinical value to depict individual aspects of wellbeing after laryngectomy. The combination of VHI and SF-36 illuminates correlations between general and special subjective aspects. Strikingly, the laryngectomies' social and psychological status is not related to their voice handicap. Data allow for conclusion that laryngectomies' substitute voice problems do not affect social aspects of quality of life in a disease specific way, at least as long as voice restoration was successful at all.

Aged↗

[Helicobacter pylori: reasons for eradication].

Helicobacter pylori infection has been recognized as the most important pathogenetic principal of peptic ulcer disease, atrophic gastritis, gastric adenocarcinoma and MALT lymphoma. At the moment efforts are made to clarify it's role in functional dyspepsia, and gastro-esophageal reflux disease. The complex interactions between H. pylori infection and NSAIDs is another field of ongoing research. Diagnosis and eradication therapy are standardized. Established indications are peptic ulcer disease, low-grade gastric MALT lymphoma, early gastric cancer treated by mucosal resection and partial gastrectomy for gastric cancer. Atrophic gastritis, known to be a precancerous lesion, as well as first degree relatives of patients with gastric cancer is another widely accepted indication for eradication therapy. The recommended eradication regimens combine a proton pump inhibitor with clarithromycin and either amoxicillin or metronidazole--for a week.

Adenocarcinoma↗

Promoter specificity in Pseudomonas aeruginosa quorum sensing revealed by DNA binding of purified LasR.

Along with their cognate acyl-homoserine lactone signals, the quorum sensing regulators LasR and RhlR control the expression of hundreds of genes in the opportunistic human pathogen Pseudomonas aeruginosa. This extensive, overlapping regulatory network affords the opportunity to systematically investigate the sequence requirements and specificity determinants of large families of target promoters. Many of the P. aeruginosa quorum-controlled genes possess conserved palindromic promoter elements predicted to be binding sites for either one or both transcriptional regulators, but biochemical proof has not been reported. We have purified native LasR and characterized binding to various quorum-controlled promoters in vitro. Purified LasR was a dimer in solution that irreversibly bound two molecules of 3-oxo-C12-homoserine lactone. LasR bound several las-responsive promoters specifically and with high affinity, interacting cooperatively with some promoters and noncooperatively with others. LasR recognized some, but not all, of the predicted binding sites, and also bound to several unexpected sites. In contrast to predictions from genetic data, we found that the recognition sequences of las-specific promoters showed little overall sequence conservation and did not require dyad symmetry. We found distinct differences in sequence composition between las-specific noncooperative, las-specific cooperative, and rhl-responsive promoters. These results provide the basis for defining promoter specificity elements in P. aeruginosa quorum sensing. Insights into the molecular mechanism of LasR function have implications for the development of quorum-sensing targeted antivirulence compounds.

Bacterial Proteins↗

[Implementation of an internal transfer pricing system for anaesthesia services].

Internal transfer pricing system (ITPS) of anaesthesia services is established to guarantee a close connection of delivered service and the budget of the department of anaesthesia. In most cases a time-based system is used with the pricing unit being calculated as the quotient from the enumerator "costs" divided by the denominator "anaesthesia time in minutes". The implementation of a transfer pricing system requires the identification of all relevant costs caused by the department of anaesthesia and a cost centre structure is needed which allocates all costs correctly according to their cause. The regulations regarding cost calculations as defined by the German DRG System should be considered. To generate valid data not only the necessary technical infrastructure is needed, but also detailed training of the staff and plausibility checks are needed to ensure correct and complete data. Subsequent agreements with the hospital administration are necessary in order to adjust the system if extrinsic cost increases occur. This paper gives a step-by-step guidance for the successful implementation of an internal transfer pricing system based on anaesthesia time.

Anesthesia Department, Hospital↗