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Biomedical subjects

S Schneider

Publications and source records attributed to S Schneider.

At least 37 records · Page 2Linked to original sources

Sirolimus-eluting stent treatment for isolated proximal left anterior descending artery stenoses. Results from the prospective multi-center German Cypher Registry.

BACKGROUND: Stenting of isolated proximal LAD stenoses is still a controversial issue since it is associated with higher target vessel revascularization (TVR) rate than both bypass surgery using the internal mammary artery, and stenting of other coronary artery territories. The sirolimus- eluting stent (SES) has been reported to significantly reduce restenosis rates in de novo coronary lesions. Therefore, we compared patients from the German Cypher Registry treated with SES for isolated proximal LAD lesions with those stented for isolated lesions in the proximal LCX or RCA. METHODS: A total of 349 patients treated with SES were analyzed. 249 patients were treated for proximal LAD stenosis, and 100 for proximal LCX/RCA stenoses. The combined clinical endpoint was MACCE (death of any cause, non-fatal MI and non-fatal stroke) and TVR at 6 months. RESULTS: In-hospital events (death, MI and TVR) did not differ significantly between both groups (3.2% for the LAD group vs 2.0% for the LCX/RCA-group, p=0.73). The combined end point of death of any cause, non-fatal MI and non-fatal stroke at six months was 2.6% in the LAD group, and 2.2% in the LCX/RCA group (p=1.0). TVR occurred in 4.8% of the LAD group and in 6.5% of the LCX/RCA group at six months (p=0.58). The percentage of patients free from angina at daily activities was 80.6% in the LAD group, and 77.4% in the LCX/ RCA group (p=0.52). CONCLUSION: SES once implanted into isolated proximal LAD stenoses appears as effective as reported in other vessel territories. Accordingly, stenting of the proximal LAD using SES might prove a suitable alternative to surgery.

Activities of Daily Living↗

[Preaching to the converted: deficits and surpluses in preventative pain therapy in German back care programs].

BACKGROUND: In response to the growing incidence of back pain, increasing emphasis is being placed on individualized preventive measures. The purpose of the present study was to investigate representative data for back pain, participation rates of back care programs, and their correlates in the German general population. METHODS: The first National Health Survey was carried out in the Federal Republic of Germany in the period from October 1997 to March 1999. It comprised a representative, cross-sectional study of the population with a total sample of 6235 participants between the ages of 18 and 79. RESULTS: The 7-day prevalence for back pain in Germany was found to be 36%, and 7% of all Germans had participated in a back care program within the past year. The 1-year participation rate was significantly lower in persons with higher risk for back pain (men, full-time workers, unmarried people, and those with an unhealthy lifestyle). CONCLUSIONS: The user profile for back care programs indicates that genuine needs are not being met and the target group is not being reached. A "preaching to the converted" phenomenon is evident, as indicated by the fact that the user group is made up of individuals who already have a healthy lifestyle and few risks while the population group most likely to develop back pain is significantly less likely to participate in preventive back care programs.

Adult↗

Towards a medically approved technology for alginate-based microcapsules allowing long-term immunoisolated transplantation.

The concept of encapsulated-cell therapy is very appealing, but in practice a great deal of technology and know-how is needed for the production of long-term functional transplants. Alginate is one of the most promising biomaterials for immunoisolation of allogeneic and xenogeneic cells and tissues (such as Langerhans islets). Although great advances in alginate-based cell encapsulation have been reported, several improvements need to be made before routine clinical applications can be considered. Among these is the production of purified alginates with consistently high transplantation-grade quality. This depends to a great extent on the purity of the input algal source as well as on the development of alginate extraction and purification processes that can be validated. A key engineering challenge in designing immunoisolating alginate-based microcapsules is that of maintaining unimpeded exchange of nutrients, oxygen and therapeutic factors (released by the encapsulated cells), while simultaneously avoiding swelling and subsequent rupture of the microcapsules. This requires the development of efficient, validated and well-documented technology for cross-linking alginates with divalent cations. Clinical applications also require validated technology for long-term cryopreservation of encapsulated cells to maintaining a product inventory in order to meet end-user demands. As shown here these demands could be met by the development of novel, validated technologies for production of transplantation-grade alginate and microcapsule engineering and storage. The advances in alginate-based therapy are demonstrated by transplantation of encapsulated rat and human islet grafts that functioned properly for about 1 year in diabetic mice.

Alginates↗

Real-time 3-D dark-field microscopy for the validation of the cross-linking process of alginate microcapsules.

Alginate-based microencapsulation is a promising method for long-term maintenance of cellular and membrane function of the cells and tissue fragments required for in vitro and in vivo biosensors, for tissue engineering and particularly for immunoisolation of non-autologous transplants. Microcapsules of high mechanical strength and optimum permeability can be produced by injection of BaCl2 crystals into alginate droplets before they come into contact with external Ba2+. A key requirement is that the system parameters (number of crystals, speed of the crystal stream etc.) are properly adjusted according to the mannuronic and guluronic acid ratio and the average molecular mass of the alginate as well as to the diameter of the microcapsules. Robust, reliable, rapid and low-cost validation tools are, therefore, needed for assurance of the microcapsule quality. Here, we describe a novel three-dimensional (3-D) dark-field microscopy that allows the real-time measurement of the number and spatial distribution of the injected Ba2+ ions throughout the microcapsules after treatment with sulphate. This novel method requires only a conventional microscope equipped with three polarising filters and a double aperture stop. In contrast to confocal laser scanning microscopy images, peripherally attached BaSO4 precipitates can clearly be distinguished from internal ones. The data also demonstrate that several steps of the alginate gelling process must be improved before such immunoisolation can be used in patients.

Alginates↗

Failure rate of frontal versus parietal approaches for proximal catheter placement in ventriculoperitoneal shunts: revisited.

Early studies on ventriculoperitoneal shunt malfunctions demonstrated that proximal catheter obstruction was the most common cause for shunt malfunction and choroid plexus was the primary culprit for catheter obstruction. Subsequently, several studies were performed using stereotactic and endoscopic guidance systems to assist with optimal placement of proximal shunt catheters. Surgeons collectively agree that optimum placement of the proximal catheter tip is away from choroid plexus in the frontal horn. To achieve this catheter placement, neurosurgeons typically choose a frontal or parietal approach. Two previous studies comparing parietal and frontal shunt failure rates in the pediatric population have different conclusions. Thus, we decided to compare proximal catheter failure rates of frontal versus parietal approaches on 117 patients (ages ranging from 1 month to 80 years) who had undergone ventriculoperitoneal shunt placement at our institution. Statistical analysis demonstrated a significantly higher malfunction rate in the patients less than 3 years of age and a lower overall malfunction rate in patients shunted for normal pressure hydrocephalus. Surprisingly, there was no significant difference between the two surgical approaches. Thus, we concluded after reviewing the literature, that regardless of the initial surgical approach, the most important variable in shunt malfunction appears to be the final destination of the catheter tip in relation to the choroid plexus.

Adolescent↗

[Diagnostic and therapeutic recommendations for mucous membrane pemphigoid of the eye].

Mucous membrane pemphigoid (MMP) is often accompanied with a chronic cicatrizing conjunctivitis that may eventually lead to loss of vision. The study is intended to investigate the current scientific knowledge on the diagnosis of and therapy for MMP involving the eye. Previous studies published before December 2004 have been systematically reviewed for their level of evidence. Consequently, recommendations for patient management are provided.

Chronic Disease↗

In vitro and in vivo evaluation of novel glibenclamide derivatives as imaging agents for the non-invasive assessment of the pancreatic islet cell mass in animals and humans.

Pancreatic islet cell mass (PICM) is a major determinant of the insulin secretory capacity in humans. Currently, the only method for accurate assessment of the PICM is an autopsy study. Thus, development of a technique allowing the non-invasive quantification of PICM is of great interest. The aim of this study was to develop such a non-invasive technique featuring novel fluorine- and (99m)Tc-labelled glibenclamide derivatives. Despite the structural modifications necessary to introduce fluorine into the glibenclamide molecule, all derivatives retained insulin stimulating capacity as well as high affinity binding to human SUR1 when compared to the original glibenclamide. Contrastingly, the lipophilicity of the fluorine-labelled derivatives was altered depending on the particular modification. In the human PET-study a constant but weak radioactive signal could be detected in the pancreas using a fluorine-labelled glibenclamide derivative. However, a reliable assessment and visualisation of the PICM could not be obtained. It can be assumed that the high uptake of the fluorine-labelled tracer e.g. into the the liver and the high plasma protein binding leads to a relatively low signal-to-noise ratio. In case of the presented fluorine-labelled glibenclamide based compounds this could be the result of their invariably high lipophilicity. The development of a (99 m)Tc-labelled glibenclamide derivative with a lower lipophilicity and differing in vivo behaviour, glibenclamide based compounds for non-invasive imaging of the pancreatic islet cell mass may be possible.

ATP-Binding Cassette Transporters↗

Quality assurance for diabetic retinopathy telescreening.

AIMS: TOSCA was an EU-Commission supported international research project designed to develop telescreening services in diabetic retinopathy and glaucoma. This paper describes the quality assurance methods developed for the diabetic retinopathy telescreening service within the TOSCA project. SETTING: The study was performed in 1895 patients with diabetes between 2000 and 2002 at diabetic retinopathy screening sites in five European countries. Data were analysed centrally. METHODS: Patients attending each clinic's diabetic retinopathy screening service received standardized retinal photography. The images and associated data were transferred electronically to a remote location for grading. Each photographer uploading images and each grader downloading images for assessment was controlled by a systematic quality management approach. The quality assurance measures defined were image quality, intragrader reliability. A cockpit chart was developed for the management and presentation of relevant results and quality measures. For the intragrader reliability tests, 10% of the images were processed for a second grading. An algorithm for calculating differences between repeated gradings was developed. RESULTS: The assessment of image quality for the different sites showed that only 0-0.7% were unassessable. One hundred per cent agreement for both gradings was achieved in 50-85% of graded cases, depending on site and grader, and an agreement better than 95% in 71-100% of cases. CONCLUSIONS: A telemedicine-supported quality assurance process is practical and advantageous. The cockpit charts have proven to be useful tools when monitoring the performance of a telescreening service. Grader feedback showed high satisfaction with the quality assurance process.

Diabetic Retinopathy↗

Continuous passive motion versus immobilisation in a cast after surgical treatment of idiopathic club foot in infants: a prospective, blinded, randomised, clinical study.

Continuous passive motion has been shown to be effective in the conservative treatment of idiopathic club foot. We wished to determine whether its use after operation could improve the results in resistant club feet which required an extensive soft-tissue release. There were 50 feet in the study. Posteromedial lateral release was performed in 39 feet but two were excluded due to early relapse. The mean age at surgery was eight months (5 to 12). Each foot was assigned a Dimeglio club foot score, which was used as a primary outcome measure, before operation and at 6, 12, 18 and 44 months after. Nineteen feet were randomly selected to receive continuous passive motion and 18 had standard immobilisation in a cast. After surgery and subsequent immobilisation in a cast the Dimeglio club foot score improved from 10.3 before to 4.17 by 12 months and to 3.89 at 48 months. After operation followed by continuous passive motion the score improved from 9.68 before to 3.11 after 12 months, but deteriorated to 4.47 at 48 months. Analysis of variance adjusted for baseline values indicated a significantly better score in those having continuous passive motion up to one year after surgery, but after 18 and 48 months the outcomes were the same in both groups.

Child, Preschool↗

Intracellular delivery of carbohydrates into mammalian cells through swelling-activated pathways.

Volume changes of human T-lymphocytes (Jurkat line) exposed to hypotonic carbohydrate-substituted solutions of different composition and osmolality were studied by videomicroscopy. In 200 mOsm media the cells first swelled within 1-2 min and then underwent regulatory volume decrease (RVD) to their original isotonic volume within 10-15 min. RVD also occurred in strongly hypotonic 100 mOsm solutions of di- and trisaccharides (trehalose, sucrose, raffinose). In contrast to oligosaccharide media, 100 mOsm solutions of monomeric carbohydrates (glucose, galactose, inositol and sorbitol) inhibited RVD. The complex volumetric data were analyzed with a membrane transport model that allowed the estimation of the hydraulic conductivity and volume-dependent solute permeabilities. We found that under slightly hypotonic stress (200 mOsm) the cell membrane was impermeable to all carbohydrates studied here. Upon osmolality decrease to 100 mOsm, the membrane permeability to monomeric carbohydrates increased dramatically (apparently due to channel activation caused by extensive cell swelling), whereas oligosaccharide permeability remained very poor. The size-selectivity of the swelling-activated sugar permeation was confirmed by direct chromatographic measurements of intracellular sugars. The results of this study are of interest for biotechnology, where sugars and related compounds are increasingly being used as potential cryo- and lyoprotective agents for preservation of rare and valuable mammalian cells and tissues.

Biological Transport↗

Binding N2, N2H2, N2H4, and NH3 to transition-metal sulfur sites: modeling potential intermediates of biological N2 fixation.

In the quest for low-molecular-weight metal sulfur complexes that bind nitrogenase-relevant small molecules and can serve as model complexes for nitrogenase, compounds with the [Ru(PiPr(3))('N(2)Me(2)S(2)')] fragment were found ('N(2)Me(2)S(2)'(2-)=1,2-ethanediamine-N,N'-dimethyl-N,N'-bis(2-benzenethiolate)(2-)). This fragment enabled the synthesis of a first series of chiral metal sulfur complexes, [Ru(L)(PiPr(3))('N(2)Me(2)S(2)')] with L=N(2), N(2)H(2), N(2)H(4), and NH(3), that meet the biological constraint of forming under mild conditions. The reaction of [Ru(NCCH(3))(PiPr(3))('N(2)Me(2)S(2)')] (1) with NH(3) gave the ammonia complex [Ru(NH(3))(PiPr(3))('N(2)Me(2)S(2)')] (4), which readily exchanged NH(3) for N(2) to yield the mononuclear dinitrogen complex [Ru(N(2))(PiPr(3))('N(2)Me(2)S(2)')] (2) in almost quantitative yield. Complex 2, obtained by this new efficient synthesis, was the starting material for the synthesis of dinuclear (R,R)- and (S,S)-[micro-N(2)[Ru(PiPr(3))('N(2)Me(2)S(2)')](2)] ((R,R)-/(S,S)-3). (Both 2 and 3 have been reported previously.) The as-yet inexplicable behavior of complex 3 to form also the R,S isomer in solution has been revealed by DFT calculations and (2)D NMR spectroscopy studies. The reaction of 1 or 2 with anhydrous hydrazine yielded the hydrazine complex [Ru(N(2)H(4))(PiPr(3))('N(2)Me(2)S(2)')] (6), which is a highly reactive intermediate. Disproportionation of 6 resulted in the formation of mononuclear diazene complexes, the ammonia complex 4, and finally the dinuclear diazene complex [micro-N(2)H(2)[Ru(PiPr(3))('N(2)Me(2)S(2)')](2)] (5). Dinuclear complex 5 could also be obtained directly in an independent synthesis from 1 and N(2)H(2), which was generated in situ by acidolysis of K(2)N(2)(CO(2))(2). Treatment of 6 with CH(2)Cl(2), however, formed a chloromethylated diazene species [[Ru(PiPr(3))('N(2)Me(2)S(2)')]-micro-N(2)H(2)[Ru(Cl)('N(2)Me(2)S(2)CH(2)Cl')]] (9) ('N(2)Me(2)S(2)CH(2)Cl'(2-) =1,2-ethanediamine-N,N'-dimethyl-N-(2-benzenethiolate)(1-)-N'-(2-benzenechloromethylthioether)(1-)]. The molecular structures of 4, 5, and 9 were determined by X-ray crystal structure analysis, and the labile N(2)H(4) complex 6 was characterized by NMR spectroscopy.

Journal Article↗

[Clinical results after Sauve-Kapandji procedure in relation to diagnosis].

We present the results of a retrospective study on 56 patients who underwent the Sauve-Kapandji procedure for chronic disorders of the distal radioulnar joint (DRUJ). Outcome was assessed with special regard to the diagnosis. The average follow-up was 5.9 years (1-12 years). Patients were assessed for pain, range of motion of wrist and forearm, and radiological features. The DASH score and Mayo wrist score were used. The diagnosis had an influence on the outcome. Patients with primary arthrosis of the DRUJ demonstrated better results than patients with traumatic disorders. Patients with growth deficiency-related complaint of the DRUJ showed slightly inferior results after the Sauve-Kapandji procedure compared to all patients. Patients were free of pain or had pain only during heavy labor in 81% of cases; 95% of the patients rated the outcome as excellent or improved, but only 50% were free of symptoms on the operated side during heavy manual labor. Symptoms of ulnar impingement were found in 11%. Improvement in range of motion of wrist and forearm was significant. The postoperative DASH score was 24.2+/-22.5 and the Mayo wrist score was 76.1+/-17.6. Our results confirm the Sauve-Kapandji procedure to be a reliable salvage procedure resulting in high patient satisfaction and reliable improvement in range of motion. However, decreased grip strength on the affected side must be accepted to some extent. The diagnosis of a DRUJ disorder influences the outcome.

Adult↗

[Pro- and supination impairments due to torsional deformities of the radial diaphysis before and after ulna osteotomy].

The aim of this experimental study was to measure the exact influence of torsional deformities at the middle third of the radial shaft before and after osteotomy of the ulnar shaft on the rotation of the forearm. Intact and fresh cadaver specimens were fixed in a newly developed apparatus that allowed free pronation and supination. A ring fixator was applied to the radial shaft with K wires that allowed torsional deformities to be stabilized in steps of 10 degrees. The middle of the radial shaft was osteotomized via a small soft tissue window leaving the other soft tissues including the interosseous membrane intact. Supination and pronation were measured using a goniometer in a standardized fashion. The mean supination value before osteotomy of the radius was 71.6 degrees [standard deviation (SD)15.2 degrees], the mean pronation value was 64.5 degrees (SD 12.4 degrees). Radial osteotomy caused no significant difference in the range of motion prior to creation of torsional deformities. Supination torsional deformities greater than 30 degrees showed a significant loss of pronation and pronation torsional deformities greater than 30 degrees resulted in a significant loss of supination in 14 fresh cadavers, respectively. The amount of mean rotational loss was approximately the same in the respective pronation and supination torsional deformities. In the next step the influence of an ulna osteotomy on the range of motion was evaluated in different torsional deformities. In the four cadavers measured, there was an increase of the range of motion in the direction of the torsional deformity. These values were not significant when compared to values before ulna osteotomy, but there were significant changes to the non deformity (p=0.004 for pronation, p=0.003 for supination). Impairment of range of motion in the opposite direction of the deformity showed a similar appearance as values before ulna osteotomy. Again, there were significant changes to the non deformity (p=0.003 for pronation, p=0.005 for supination).

Adult↗

"Real life" use of sirolimus-eluting coronary stents in Germany. Results from the prospective multi-centre German Cypher Registry.

BACKGROUND: Drugeluting stents (DES) are currently judged to be a "break-through" technology for the prevention of restenosis after percutaneous coronary interventions (PCI). However, experience is limited to randomised controlled clinical trials (RCT) in selected lesions and the currently available DES are more expensive compared to conventional "bare" stents. Therefore, actual clinical practice may be very different to RCT. METHODS: We analysed the data of the German Cypher trade mark Registry, a nationwide registry which was initiated in parallel to the launch of the first DES, the Cypher trade mark sirolimus-eluting coronary stent, in April 2002. RESULTS: From April 2002 until March 2003, 1638 procedures at 88 hospitals were included in the German Cypher trade mark Registry. The mean inclusion rate per centre and month remained low (<3 procedures/month and participating hospital) during the whole inclusion period. Most patients presented with stable angina pectoris (45.8%); however, 6.4% of patients were treated for a non-ST elevation myocardial infarction, 10.3% of patients for ST elevation myocardial infarction and 1.7% in cardiogenic shock. In patients without ST elevation myocardial infarction, a de novo stenosis was treated in 68.4% of cases, a restenosis in 4.1%, and an in-stent restenosis in 25.5% of cases. Chronic total occlusions were treated in 6.1% of patients. Predilatation was performed in 68.3% of patients and 1.05 +/- 0.35 Cypher trade mark stents were implanted per patient with a median (quartiles) stent length of 18 (13-21) mm. PCI-related death occurred in 0.1% of patients and a Q-wave myocardial infarction in 1.1%. Urgent re-PCI before hospital discharge was performed in 1.3% and urgent bypass surgery in 0.1% of cases. CONCLUSIONS: The use of the sirolimus-eluting coronary stents in this "real life" registry was found to be safe concerning acute complications. In about one half of the registry patients, the DES was implanted in lesions that were excluded from RCTs.

Blood Vessel Prosthesis↗

A mycotic aneurysm of the ascending aorta and aortic arch induced by Salmonella Enteritidis.

In very rare cases, salmonella infection may be associated with extra-intestinal manifestations. Of these, a mycotic aneurysm represents a life-threatening complication that is characterised by a high mortality rate. Prompt treatment with a combination of antibiotic therapy and surgical intervention is urgently required. We report on the case of a 60-year-old woman who presented with salmonella bacteraemia and the rare complication of an infected aneurysm of the ascending aorta and aortic arch.

Aneurysm, Infected↗

Synthesis and evaluation of (S)-2-(2-[18F]fluoroethoxy)-4-([3-methyl-1-(2-piperidin-1-yl-phenyl)-butyl-carbamoyl]-methyl)-benzoic acid ([18F]repaglinide): a promising radioligand for quantification of pancreatic beta-cell mass with positron emission tomography (PET).

18F-labeled non-sulfonylurea hypoglycemic agent (S)-2-(2-[(18)F]fluoroethoxy)-4-((3-methyl-1-(2-piperidin-1-yl-phenyl)-butylcarbamoyl)-methyl)-benzoic acid ([(18)F]repaglinide), a derivative of the sulfonylurea-receptor (SUR) ligand repaglinide, was synthesized as a potential tracer for the non-invasive investigation of the sulfonylurea 1 receptor status of pancreatic beta-cells by positron emission tomography (PET) in the context of type 1 and type 2 diabetes. [(18)F]Repaglinide could be obtained in an overall radiochemical yield (RCY) of 20% after 135 min with a radiochemical purity higher than 98% applying the secondary labeling precursor 2-[(18)F]fluoroethyltosylate. Specific activity was in the range of 50-60 GBq/micromol. Labeling was conducted by exchanging the ethoxy-moiety into a 2-[(18)F]fluoroethoxy group. To characterize the properties of fluorinated repaglinide, the affinity of the analogous non-radioactive (19)F-compound for binding to the human SUR1 isoform was assessed. [(19)F]Repaglinide induced a complete monophasic inhibition curve with a Hill coefficient close to 1 (1.03) yielding a dissociation constant (K(D)) of 134 nM. Biological activity was proven via insulin secretion experiments on isolated rat islets and was comparable to that of repaglinide. Finally, biodistribution of [(18)F]repaglinide was investigated in rats by measuring the concentration of the compound in different organs after i.v. injection. Pancreatic tissue displayed a stable accumulation of approximately 0.12% of the injected dose from 10 min to 30 min p.i. 50% of the radioactive tracer could be displaced by additional injection of unlabeled repaglinide, indicating that [(18)F]repaglinide might be suitable for in vivo investigation with PET.

ATP-Binding Cassette Transporters↗