FK 506 and successful pregnancy in a patient after renal transplantation.
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Biomedical subjects
Publications and source records attributed to W Müller.
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We recently showed that the C-terminal fragment PTH (52-84) effectively increases intracellular free calcium ([Ca2+]i) in a subset of growth plate chondrocytes not activated by the N-terminal PTH fragment (1-34). Here we characterize the active site on C-terminal PTH (52-84) with respect to calcium (Ca2+)-signaling and the mechanism involved by using synthetic PTH-subfragments in digital CCD ratio-imaging experiments. Our results show amino acids 73-76 to be the core region for increasing [Ca2+]i. Ryanodine (1 microM), caffeine (10 mM), lithium (2 mM), or cyclopiazonic acid (2-5 microM), agents that interfere with intracellular Ca2+ release, all failed to block PTH (52-84) induced [Ca2+]i increases. Depletion of extracellular calcium ([Ca2+]o) blocked PTH (52-84) induced [Ca2+]i increases, indicating a transmembrane Ca2+ influx. In contrast to voltage-gated and Ca2+ release activated Ca2+ influx, PTH (52-84) evoked Ca2+ influx was not blocked by nickel (1 mM). We conclude that PTH amino acids 73-76 are essential for activation of a nickel-insensitive Ca2+ influx pathway in growth plate chondrocytes that is likely to be of relevance for matrix calcification, a key step in endochondral bone formation.
Aspiration before local anaesthesia is essential to avoid an incorrectly placed needle. We tested 142 types of cannula in mucobuccal preparations from 29 cadavers. The cannulas were obtained from 23 different firms and the formation of punch cylinders caused by injection was studied at angles of penetration of 70 degrees and 90 degrees. The force of puncture was measured by a computer-controlled apparatus. In a second series of tests the aspirating ability of 121 cannulas with self-aspirating and actively aspirating syringes was tested in vitro. The results show that false negative aspirations are caused by: using a cannula that is too small (<= 27 Gauge); the cannula lumen becoming clogged with tissue punch cylinders; using a Carpule needle end that is too short to perforate the rubber of the ampoule; containing rubber fragments in the back of the Carpule needle end; and using an injection syringe with too small a viewport when the injection syringe was positioned at a 90 degrees. We recommend the construction of a system in which the distance between the cone and viewport is reduced.
PURPOSE: Sonographically-guided Radio-Frequency Tissue Ablation-applied with a percutaneously placed needle can be used for the palliative treatment of primary or secondary liver tumours. In vitro experiments were carried out to establish the relations of the coagulation zone to histologic findings and sonographic appearance. METHOD: Fresh bovine livers were obtained and radio-frequency was applied under ultrasound guidance. The coagulation zone was dissected and examined by determining its three-dimensional diameters (macroscopically) and the histologic appearance of the coagulation margin to the surrounding tissue. In our series of 50 experiments the application time ranged from 30 seconds to 10 minutes. RESULTS: The coagulation zone increased with increasing application time in a way that can be described as a negative logarithmic function. The largest volume was 4 x 5 x 5 cm (length, width, depth) approximating 50 ml. It was no problem to judge the coagulation zone sonographically. The macroscopically and sonographically determined width and length correlated with coefficients of 0.90 and 0.96. Microscopically the coagulation necrosis showed sharply outlined margins without any vital cells. CONCLUSION: Radio-Frequency Tissue Ablation applied under sonographic guidance has certain features which seem to make it a promising method for the palliative treatment of primary and secondary tumours of the liver.
Cyclical fluctuations in cerebral blood flow velocity in Doppler measurements are a well known phenomenon. In 1992 Livera et al have shown in one patient, that cyclical fluctuations of cerebral blood volume could be measured with near infrared spectroscopy (NIRS). The aim of the present study was a quantification of the amplitude of cyclical fluctuations of cerebral blood volume (represented by total haemoglobin [Hbtot]) in a large number of healthy infants. Furthermore changes of oxygenated haemoglobin (HbO2) and deoxygenated haemoglobin (Hb) were investigated. Measurements were done during two hours of undisturbed daytime sleep. Fifty-eight infants (30 male, 28 female) were included in the study. All but one infant showed cyclical fluctuations. For quantification of cyclical fluctuations only periods during quiet sleep with excellent tracing quality were used. A number of 7894 cycles was analyzed for each of the three NIRS parameters. The median amplitude of the cycling fluctuations was: delta Hbtot 1.1 mumol/l, delta HbO2 1.1 mumol/l, and delta Hb 0.2 mumol/l. The frequency was changing within a range of 3 to 6 cycles/minute. Polynominal regression analysis showed that the relationship of delta HbO2 and delta Hbtot was distinctively stronger compared to the relationship of delta Hb and delta Hbtot. In conclusion we think that these data represent "normal ranges" for parameter fluctuations in long-time NIRS tracings.
BACKGROUND: Traditional training methods for surgeons include anatomical studies on human cadavers. Limited availability and ethical problems led to the consideration of alternatives. The surgeon's level of training could be significantly increased by a interactive training system trough computer graphics and virtual reality (VR). METHODS: Two main issues addressed are the 3-D reconstruction process and 3-D interaction to guide the surgical instruments. To provide the virtual environment, a realistic representation of the region of interest with all relevant anatomical parts is required. This model has to be suitable for computer simulation, while preserving as accurately as possible important anatomic features. Therefore the concept of creating a 3-D representation semi-automatically was developed. Textures derived from endoscopic images are superimposed on the virtual anatomic structures and provide better realism. RESULTS: Intuitive handling of the surgical instruments is ensured by using the tracking technique. The system allows navigation via a virtual camera and interaction with the virtual anatomical structures. Currently the use of a force feedback system and the simulation of deformations of tissues is critical. CONCLUSIONS: The VR based simulation system offers an alternative to conventional training methods. The future role of surgical simulation depends on overcoming the current drawbacks to provide greater interactive realism: the integration of a force feedback system to simulate the resistance of anatomical structures and the simulation of tissue deformations--both currently under development.
Liver diseases of infancy and childhood are generally rare and within the spectrum of these disorders, only a few subtypes are related to abnormal hepatic copper accumulation. Idiopathic copper toxicosis has been defined as such a subtype; although this disease is characterized by distinct clinical and pathologic features, its exact etiology is still controversial. On the basis of a review of the literature, supplemented by our own observations of 138 cases endemic to western Austria, we hypothesize that idiopathic copper toxicosis is caused by a synergy of an autosomal-recessive inherited defect in copper metabolism and excess dietary copper. Increased awareness of the disease should enable early diagnosis and lead to successful treatment, thereby improving the overall poor prognosis of affected patients.
The functional receptor for the inflammatory cytokine IL-6 is composed of the ligand binding IL-6 receptor alpha chain (IL-6R alpha) and the signal transducing chain gp130, which is a shared component of multiple cytokine receptors. We analyzed the surface expression of gp130 and IL-6R alpha in thymocytes and peripheral T cells. While all thymocytes expressed gp130 throughout thymic maturation, they gained expression of IL-6R alpha at the CD4 or CD8 single-positive stage. Approximately 10-30% of the CD4-CD8+ and 40-50% of the CD4+CD8- thymocytes expressed IL-6R alpha. Within the CD4+CD8- population, the IL-6R alpha- subpopulation was cortisone sensitive, appeared immature according to the cell surface markers expressed and failed to proliferate after TCR cross-linking. Peripheral T cells were predominantly gp130+ and IL-6R alpha+, but down-regulated gp130 and IL-6R alpha expression upon TCR engagement in vitro and in vivo. Peripheral gp130low/-IL-6R alphalow/- T cells expressed surface markers characteristic of memory T cells. We show that gp130 and IL-6R alpha are expressed in a regulated manner in T cells, depending on the developmental and functional stage.
OBJECTIVE: The efficacy of an integrated, psychological treatment program was tested in a controlled study involving 27 patients with chronic musculoskeletal pain (fibromyalgia). DESIGN: The experimental treatment program consisted of instruction in various self-help techniques (e.g., cognitive behavioral strategies, relaxation, physical exercises) as well as information on chronic pain. Control groups were instructed only in autogenic training. Measures of pain, daily activities, general symptoms, and psychological functioning were assessed before and after treatment, as well as at 4 months after termination of therapy (follow-up). RESULTS: At the end of treatment, 7 patients from the experimental group and 2 from the control group showed significant clinical improvement in 3 of 6 parameters (NS). At follow-up, the improvement was still present in 5 experimental cases but in none of the controls (p = 0.024). Successful patients had been sick for a shorter period of time and were less impaired by their condition. CONCLUSIONS: Psychological interventions in combination with physiotherapy can be effective in treating fibromyalgia patients, especially if applied early.
Apolipoprotein E (apoE) is the major apolipoprotein in the brain and is known for its important role in plasticity and neurodegeneration. We show that apoE dose-dependently increases intracellular free Ca2+ in rat hippocampal astrocytes and neurons. This effect varies with isoforms in the order E4 > E3 > E2. It is insensitive to blockade of action potentials by tetrodotoxin or inhibition of binding of apoE by heparinase, by the LRP ligand lactoferrin and by low density lipoprotein. ApoE evoked Ca2+-increases are blocked in zero [Ca]o and by the Ca-channel antagonists nickel and omega-Agatoxin-IVa but not by nifedipine and omega-Conotoxin-GVIa, demonstrating an isoform-specific activation of P/Q type Ca2+-channels. This novel mechanism is discussed with respect to Alzheimer's disease, that is linked for most cases to the apoE epsilon-allelic variation (epsilon4 > epsilon3 > epsilon2).
Serum samples from 996 dogs in Switzerland were examined for antibodies to Ehrlichia canis and to the agent causing canine granulocytic ehrlichiosis (CGE). Ehrlichiosis, borreliosis, and systemic illness not associated with ticks were suspected in 75, 122, and 157 of these dogs, respectively. The remainder of the serum samples were obtained from clinically healthy dogs which resided north (n = 235) or south (n = 407) of the Alps. The serum samples were tested by an indirect immunofluorescence technique for antibodies to the two agents incriminated, E. canis and Ehrlichia phagocytophila, a surrogate marker of the agent of CGE. Twenty-two of 996 (2.2%) serum samples had antibodies to E. canis and were distributed as follows: 20 of 75 (26.7%) samples from dogs suspected of having ehrlichiosis, 1 of 122 (0.8%) from dogs suspected of having borreliosis, and 1 of 407 (0.2%) from healthy dogs which resided south of the Alps. Of the 75 (7.5%) serum samples that had antibodies to E. phagocytophila, significantly more samples were from ill dogs than from healthy dogs. Among the sera from healthy dogs, antibodies to E. phagocytophila were significantly more prevalent in the north. Because seropositive dogs had a history of travel outside Switzerland and because Rhipicephalus sanguineus is found exclusively south of the Alps, it was presumed that, in contrast to the agent of CGE, E. canis is not indigenous to Switzerland.
Arthroscopy has already become an irreplaceable method in diagnostics. The arthroscope, with optics and light source, and the exploratory probe are inserted into the knee joint through two small incisions underneath the patella. Currently, the skills required for arthroscopy are taught through hands-on clinical experience. As arthroscopies became a more common procedure even in smaller hospitals, it became obvious that special training was necessary to guarantee qualification of the surgeons. On-the-job training proved to be insufficient. Therefore, research groups from the Berufsgenossenschaftliche Unfallklinik Frankfurt am Main approached the Fraunhofer Institute for Computer Graphics to develop a training system for arthroscopy based on virtual reality (VR) techniques. Two main issues are addressed: the three-dimensional (3-D) reconstruction process and the 3-D interaction. To provide the virtual environment a realistic representation of the region of interest with all relevant anatomical structures is required. Based on a magnetic resonance image sequence a realistic representation of the knee joint was obtained suitable for computer simulation. Two main components of the VR interface can be distinguished: the 3-D interaction to guide the surgical instruments and the 2-D graphical user interface for visual feedback and control of the session. Moreover, the 3-D interaction has to be realized by means of Virtual Reality techniques providing a simulation of an arthroscope and an intuitive handling of other surgical instruments. Currently, the main drawback of the developed simulator is the missing of haptic perception, especially of force feedback. In cooperation with the Department of Electro-Mechanical Construction at the Technical University Darmstadt a haptic display is designed and built for the VR arthroscopy training simulator. In parallel we developed a concept for the integration of the haptic display in a configurable way.
IMGT, the international ImMunoGeneTics database is an integrated database specializing in Immunoglobulins (Ig), T-cell receptors (TcR) and MHC molecules of all vertebrate species, created by Marie-Paule Lefranc, University of Montpellier, CNRS, Montpellier, France (Nucleic Acids Research, Database issue, Vol 26, January 1998). IMGT includes three databases: LIGM-DB (for Ig and TcR), MHC/HLA-DB and IMGT/PRIMER-DB (an Ig, TcR and MHC-related primer database), the last two in development. IMGT comprises expertly annotated sequences and alignment tables. LIGM-DB contains more than 24.000 Immunoglobulin and T cell Receptor sequences from 81 different species. MHC/HLA-DB contains class I and class II Human Leucocyte Antigen alignment tables. An IMGT tool, DNAPLOT, developed for Ig, TcR and MHC sequence analysis, is also available. IMGT goals are to establish a common data access to all immunogenetics data, including nucleotide and protein sequences, oligonucleotide primers, gene maps and other genetic data of Ig, TcR and MHC molecules, from all species, and to provide a graphical user friendly data access. IMGT has important implications in medical research (repertoire in autoimmune diseases, AIDS, leukemias, lymphomas), therapeutical approaches (antibody engineering), genome diversity and genome evolution studies. In this paper, we describe our approach for the data modelisation, the automation of the annotation procedure and control of data quality in LIGM-DB database. IMGT is freely available on the CNUSC WWW server at Montpellier: http://imgt.cnusc.fr: 8104 (contact: Denys.Chaume@cnusc.fr) and on the EBI servers: http://www.ebi.ac.uk/imgt (contact: malik@ebi.ac.uk) and ftp.ebi.ac.uk/pub/databases/imgt. LIGM-DB users are encouraged to report errors or suggestions to giudi@ligm.crbm.cnrs-mop.fr. IMGT initiator and coordinator: Marie-Paule Lefranc, lefranc@ligm.crbm.cnrs-mop.fr. (fax: +33(0)467040231).
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OBJECTIVE: The sensitivity of conventional cytology for identification of neoplastic cells in effusions is unsatisfactory, about 58%. The rate of diagnostically equivocal effusions in routine cytology is about 6%. DNA aneuploidy has previously been proven to be a sensitive and specific marker for the identification of tumor cells in effusions. In the present study we determined if malignancy can be identified in cytologically equivocal cells in effusions using DNA aneuploidy as a marker, thus decreasing the rate of cytologically equivocal diagnoses in effusions. STUDY DESIGN: One hundred cytologically equivocal effusions of the serous cavities were obtained from routine diagnostic material. Nuclear DNA content was measured after Feulgen staining using a TV image analysis system. Data were correlated with patient follow-up. RESULTS: DNA aneuploidy was assumed if abnormal DNA stemlines, a coefficient of variation of the first DNA stemline > or = 10% or cells > 9c were observed. The sensitivity of DNA aneuploidy for the identification of malignancy was 55.9%. Specificity of DNA nonaneuploidy for benignity was 94.1%. The positive predictive value of the marker DNA aneuploidy for the occurrence of malignant cells was 97.9% since all but one DNA aneuploid case showed malignancy in follow-up. CONCLUSION: Image cytometry applying DNA aneuploidy as a parameter is able to detect the occurrence of malignant cells in cytologically equivocal effusions in about every second case. Thus, this method is able to increase diagnostic accuracy of conventional effusion cytology by decreasing the rate of diagnostically equivocal effusions.
Developed by Orthotronic Medizintechnik GmbH, the so-called Triflexometer, version 3.22 was tested for its reliability and validity in measuring spinal posture and mobility. Reliability studies on 20 healthy subjects have shown this measurement method to be reliable, yet intra- and inter-rater reliability analyses also revealed that even for this healthy population discrepancies in the various measures may occur, both due to differences in compliance as well as fatigue and learning effects, and due to difficulties in stabilization of the normal posture, to a lesser extent due to certain specifics of the measurement technique (placing the markers, guiding the sensor). In total spinal immobility (ankylosing spondylitis), practically identical measurements are found, as is the case in dummy studies. The validity study on 20 healthy subjects found good correlations between the measurements obtaining using the triflexometer and those for double inclinometer, respectively, and that only minor mean value differences occur for the two methods. Also, triflexometer measurements for total anteflexion were found to correlate with those determined with the fingertip-to-floor method, no correlation was present however between the Triflexometer values and the Schober test. Triflexometer measurements performed on 114 healthy subjects of various ages served to prove that the range of spinal movement in the directions measured (sagittal and frontal) will reduce with age. To a lesser extent, this also applies to hip movement. Overall, our findings prove the triflexometer an easy-to-handle system which possesses high reliability and is suitable for valid and objective noninvasive assessment of global and segmental spinal mobility. Triflexometer examinations are highly uncomplicated to implement, and print-outs of the results obtained permit lasting documentation of the present status.
In the vicinity of the river Aquidabán in Eastern Paraguay occurred in the last years an endemic disease within cattle herds which killed thousands of heads (Mal de Aquidabán [MdA]). The disease was seen in form of an afebrile, paralytic condition characterized by muscle tremors, swaying of the hind quarters, recumbence and sudden death of the animals. Therefore it was described as "Bovine Paraplegic Syndrome". Comparable symptoms in adult cattle have also being seen in Eastern and Central Venezuela. After we found in the peritoneal fluid of 2 animals, which died under typical symptoms, toxins of C. perfringens toxovar D, we started to investigate the occurrence of C. perfringens in the feces of clinical healthy animals on farms, where MdA was diagnosed before. There we found 73% of the isolated strains belonging to toxovar D. In herds with no case of the disease toxovar A was isolated up to 90%. The next step was the production of a vaccine (anaculture) with a high toxin producing strain of C. perfringens toxovar D. 2000 cattle were vaccinated for 3 years twice a year. None of the vaccinated animals diseased. In 2 control-herds some cases of MdA occurred. But we became quite sure that MdA was an infectious disease, when we started to vaccinate cattle of unvaccinated herds where MdA suddenly occurred. One or two animals died in the next 2 days and after this period the endemic disease was immediately stopped.
In this study, microsatellite instability (MI) was investigated in 126 gastric carcinomas and correlated with clinicopathological features and prognosis; at least 5-10 microsatellite loci were analyzed. MI was identified in 56 (44.5%) of all investigated carcinomas, one locus being affected in 40 (31.7%) carcinomas, two loci being affected in 6 (4.8%) carcinomas, and more than two loci being affected in 10 (8.0%) carcinomas. MI was correlated with neither age and sex of the patients nor with depth of invasion, lymph node metastasis, tumor differentiation, or histological type according to WHO and Laurén classification. The frequency of MI was the same in early gastric carcinomas as it was in advanced gastric carcinomas, suggesting that MI arises early during the tumorigenesis of gastric cancer. No significant differences in survival could be demonstrated between patients with MI-negative and MI-positive gastric carcinomas.