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Biomedical subjects

M Grunewald

Publications and source records attributed to M Grunewald.

11 recordsLinked to original sources

[HNORAD].

BACKGROUND: New media are gaining importance in undergraduate as well as postgraduate and continued medical education. We aimed to create an interactive educational program for imaging diseases of the ear, nose and throat (ENT). MATERIALS AND METHODS: Cases and images representing clinical routine were collected, arranged by content and graphically presented according to instructional criteria. Undergraduate students participating in the project used an authoring system to generate case studies, which were then published at http://www.HNORAD.de. RESULTS: HNORAD is an interdisciplinary teaching program offering more than 100 classical disease presentations. Three systematic indices offer a choice of instructional approach. Apart from typical images, the information presented includes patient history, clinical findings, imaging findings as described by a board-qualified radiologist, diagnosis, differential diagnosis and internet links. Elements of the radiologist's report are linked with the images in such a way that the structure or finding described can be interactively highlighted. An evaluation index allows proficiency testing in self study and as a part of taught courses. CONCLUSION: HNORAD is a valuable resource for students, ENT surgeons and radiologists at the undergraduate, postgraduate and CME level for self study as well as for course work.

Computer-Assisted Instruction↗

[Quality improvement of resources in radiology on the internet].

PURPOSE: Categorization and evaluation of online teaching files in radiology by representative members of the target group to make the specific search for adequate programs more effective. MATERIALS AND METHODS: A representative team of board qualified radiologists, residents and medical students performed a basic search for radiology teaching files on the Internet using search machines, international mailing lists and link lists to collections of national and international radiological societies and departments. The programs were categorized by language, modality, target group and special features, such as qualification for CME-accreditation. For final evaluation and ranking of the detected files, a questionnaire was developed to assess completeness, image quality, page loading time, layout, orientation, interactivity, annotation and maintenance. The results were stored in an Access database on a web server. A query form in HTML format, including the parameters described above, was made accessible to the online user. RESULTS: A search machine for radiological teaching files (RadList/Entity-link List) was made available online ( www.tnt-radiology.de/radlist and www.tnt-radiology.de/entitylinklist ). A submitted request calls a cgi script that searches the database for the appropriate sites according to the individual search parameters selected by the user. The list of matching URLs is returned to the user as HTML page. Evaluating the single sites by applying the criteria listed above contributed to the quality assurance of the radiological teaching resources on the Internet. CONCLUSION: Adapting a new Internet interface to the particular needs of the user allows a more effective access to specific radiological teaching files online. RadList/Entity-link List ( www.tnt-radiology.de/radlist and www.tnt-radiology.de/entitylinklist ) is conducive to quality improvement and benefits users as well as authors of radiological teaching files on the Internet.

Computer-Assisted Instruction↗

[Web-based training in radiology - student course in the Virtual University of Bavaria].

PURPOSE: The ninth version of the licensing regulation for medical doctors (Approbation Regulation (AR)) sets a benchmark in terms of practical experience, interdigitation of preclinical and clinical studies, interdisciplinary approach, economic efficiency, independence of students, added new teaching and learning modalities, and ongoing evaluation of the progress of the medical students. It is the aim to implement these major points of the AR in a model course for diagnostic radiology and radiation protection within the scope of the Virtual University of Bavaria and test them in practice. MATERIALS AND METHODS: In cooperation with residents and board certified radiologists, students developed the virtual course "Web-Based Training (WBT) Radiology" in diagnostic radiology and radiation protection for students in the first clinical semester. A representative target group taken from the student body was asked about the options to get access to the World Wide Web (Internet), and the satisfaction concerning configuration and content of the newly developed program. A comparison was made between the results of the final examination taken by students who made use of the virtual course in addition to conventional lessons and taken by students who did not subscribe to the virtual course and exclusively relied on conventional lessons. In addition, a pilot study was conducted in the winter semester 2002/03, which compared students taking either the traditional lessons or the new virtual course on the Internet. RESULTS: The virtual course-model had test results with a positive trend. All targeted students had Internet access. Constructive criticism was immediately implemented and contributed to rapid optimization. The learning success of the additive or alternative virtual course was in no way less than the learning success achieved with the conventional course. CONCLUSION: The learning success as measure of quality in teaching and the acceptance by students and teachers justify the continuation of this course model and its expansion. Besides enabling the learning in small study groups; the course "WBT Radiology" might not only help implementing the major points of the new AR but might also complement any deficiencies in the current education. Economic aspects may encourage their implementations.

Computer-Assisted Instruction↗

[Pseudoaneurysm of the hepatic artery--a rare complication after orthotopic liver transplantation].

INTRODUCTION: Pseudoaneurysm of the hepatic artery is a rare complication of liver transplantation, the most common cause of which--apart from technical surgical problems--is an infection. The most common symptoms are rupture and hemorrhage. METHOD: The present case report describes an asymptomatic pseudoaneurysm of the hepatic artery following liver transplantation, and its treatment. RESULTS: In this patient, an pseudoaneurysm involving an eroded branch of the hepatic artery was found. Surgical treatment consisted in the excision of the aneurysm and oversewing of the branch of the hepatic artery. CONCLUSION: The potential for rupture and hemorrhage makes surgical intervention mandatory even in asympotomatic patients with pseudoaneurysm of the hepatic artery. The surgical procedure depends on the local situation and the time elapsed since transplantation. Preservation or reconstruction of the arterial perfusion is essential.

Aneurysm, False↗

The accessibility of a novel reentrant loop of the glutamate transporter GLT-1 is restricted by its substrate.

The excitatory neurotransmitter glutamate is removed from the synaptic cleft by several related sodium- and potassium-coupled transporters. They thereby restrict the neurotoxicity of this transmitter. Based on the accessibility of single cysteines to the large sulfhydryl reagent 3-N-maleimidyl(propionyl)biocytin, we have proposed a topological model for the astroglial glutamate transporter GLT-1 (Grunewald, M., Bendahan, A. and Kanner, B. I. (1998) Neuron 21, 623-632). Because of several unexpected observations, we have investigated the topological disposition of 19 cysteine residues engineered into a loop proposed to be intracellular. We have probed the accessibility of these cysteines to small and large sulfhydryl reagents. The impermeant hydrophilic sulfhydryl reagent [(2-trimethylammonium)ethyl] methanethiosulfonate inhibits transport activity only at two of these positions, weakly at G365C and potently at A364C. Glutamate and its nontransportable analogue dihydrokainate markedly protect A364C transporters against this impermeant reagent. Using a biotinylated maleimide, we found that, among the 14 mutants tested with it, only A364C is accessible to it from the extracellular side. This, together with our previous observations, indicates that the loop-including amino acid residues 354, 359, 373, and 379-is largely intracellular, but a short region of it forms a reentrant pore-loop-like structure, the accessibility of which is dependent on the conformation of the transporter.

ATP-Binding Cassette Transporters↗

Cysteine scanning of the surroundings of an alkali-ion binding site of the glutamate transporter GLT-1 reveals a conformationally sensitive residue.

Glutamate transporters remove this transmitter from the extracellular space by cotransport with three sodium ions and a proton. The cycle is completed by translocation of a potassium ion in the opposite direction. Recently we have identified two adjacent amino acid residues of the glutamate transporter GLT-1 that influence potassium coupling. Using the scanning cysteine accessibility method we have now explored the highly conserved region surrounding them. Replacement of each of the five consecutive residues 396-400 by cysteine abolished transport activity but at several other positions the substitution is tolerated. One residue, tyrosine 403, was identified where cysteine substitution renders the transporter sensitive to modification by positively charged methanethiosulfonate derivates in a sodium-protectable fashion. In the presence of sodium, the nontransported glutamate analogue dihydrokainate potentiated the covalent modification, presumably by binding to the glutamate site and locking the protein in a conformation in which tyrosine 403 is accessible from the external bulk medium. In contrast, transported substrates significantly slowed the reaction, suggesting that during the transport cycle residue 403 becomes occluded. On the other hand, transportable substrates are not able to protect Y403C transporters against N-ethylmaleimide, which is highly permeant but unable to modify cysteine residues buried within membrane proteins. These results indicate that tyrosine 403 is alternately accessible from either side of the membrane, consistent with its role as structural determinant of the potassium binding site.

ATP-Binding Cassette Transporters↗

Adenocarcinoma in an ileal pouch after prior proctocolectomy for carcinoma in a patient with ulcerative pancolitis.

We report the first known case of pouch carcinoma in a 35-year-old female patient following proctocolectomy for adenocarcinoma in ulcerative pancolitis with backwash ileitis. Pouch cancer was diagnosed 2 years after the pelvic pouch procedure, illustrating that there might be a risk of pouch cancer in such patients. Adenocarcinoma arising in an ileoanal reservoir is rare. Two other cases have been reported: both patients concerned were believed to have developed cancer in small areas of residual remaining rectal mucosa.

Adenocarcinoma↗

Biotinylation of single cysteine mutants of the glutamate transporter GLT-1 from rat brain reveals its unusual topology.

In the central nervous system, (Na+ + K+)-coupled glutamate transporters restrict the neurotoxicity of this transmitter and limit the duration of synaptic excitation at some synapses. The various isotransporters exhibit a particularly high homology in an extended hydrophobic domain of ill-defined topology that contains several determinants involved in ion and transmitter binding. Here, we describe the determination of the membrane topology of the cloned astroglial glutamate transporter GLT-1. A series of functional transporters containing single cysteines was engineered. Their topological disposition was determined by using a biotinylated sulfhydryl reagent. The glutamate transporter has eight transmembrane domains long enough to span the membrane as et heiices. Strikingly, between the seventh and eighth domains, a structure reminiscent of a pore loop and an outward-facing hydrophobic linker are positioned.

ATP-Binding Cassette Transporters↗

[The status of diagnosis of Barrett esophagus. An analysis of 1000 histologically diagnosed cases].

OBJECTIVE: To evaluate the quality of diagnosis in cases of Barrett's oesophagus (BOe). It was examined whether: (1) there had been regular pre-treatment investigations;(2) characteristic mucosal changes had been recognized by endoscopy; (3) a diagnosis of intraepithelial neoplasia had been made more often than of advanced Barrett carcinoma. PATIENTS AND METHODS: Endoscopic and associated bioptic reports on 1000 consecutive patients with histologically confirmed BOe, seen between 1990 and 1995, were analysed. (Average age was 63 +/- 14.3 years; male to female ratio: 2.2:1). RESULTS: In 85.1% of patients the histological diagnosis was BOe without dysplasia. The neoplasias consisted of carcinoma in 8.8%, suspected carcinoma in 0.5%, actual or suspected low-grade dysplasia in 4.6%, actual or high-grade dysplasia in 1.0%. Endoscopic diagnosis in cases without neoplasia was in 60.8% correct for actual BOe or suspected BOe. At endoscopy dysplasia was suspected in 5.4%. The diagnosis or suspected diagnosis of Barrett's carcinoma was correct in 69%. Repeat endoscopy a year after the initial diagnosis was performed in 9.4% with BOe and no neoplasia. Repeat endoscopy was performed in 37.5% of patients with an initial diagnosis of suspected low-grade dysplasia, in 43.3% with low-grade dysplasia, in 42.9% of suspected high-grade and in 100% of actual high-grade dysplasia. CONCLUSION: Neoplasia in Barrett's oesophagus is found too late. Only half of the histologically confirmed cases are found by endoscopy and follow-up is not sufficient.

Aged↗

Conformational changes monitored on the glutamate transporter GLT-1 indicate the existence of two neurotransmitter-bound states.

Membrane vesicles from rat brain have been subjected to trypsin treatment in the absence and presence of substrates of the (Na+ + K+)-coupled L-glutamate transporter GLT-1. The fragments of this transporter have been detected upon immunoblotting employing several antibodies raised against sequences from this transporter. At the amino terminus, initially a fragment of an apparent molecular mass of 30 kDa is generated. This fragment is subsequently cleaved to one of 16 kDa. The generation of these bands is greatly inhibited in the presence of lithium. Moreover, lithium abolishes the positive cooperative activation of the transporter by sodium. The generation of the 30- and 16-kDa fragments is accelerated in the presence of L-glutamate and other transportable analogues, provided sodium is present as well. The 30-kDa fragment also contains an epitope from the loop connecting the putative membrane-spanning alpha-helices 3 and 4. This epitope, in contrast with the amino-terminal one, is destroyed with time. The carboxyl-terminal epitope is predominantly located on a 43-kDa fragment which is slowly converted to one of 35 kDa. This conversion is not inhibited by lithium. It is, however, stimulated by L-glutamate and other transportable analogues, but only in sodium-containing media. Potassium also stimulates this conversion regardless of the presence of L-glutamate. The stimulation of generation of amino- and carboxyl-terminal fragments by L-glutamate is not mimicked by the nontransportable analogue dihydrokainate. However, the analogue blocks the stimulation exerted by L-glutamate. In addition to new experimental information on the transporters topology, our observations provide novel information on the function of the GLT-1 transporter. Although lithium by itself does not sustain transport, it may occupy one of the sodium sites and be transported. Furthermore, the transporter-glutamate complex appears to exist in at least two states. After the initial binding (suggested to be important for the decay of synaptic glutamate), it undergoes a conformational change which represents, or is tightly associated with, the transport step.

ATP-Binding Cassette Transporters↗