Involvement of ADAM10 in axonal outgrowth and myelination of the peripheral nerve

The disintegrin and metalloproteinase 10 (ADAM10) is a membrane‐anchored metalloproteinase with both proteolytic and disintegrin characteristics. Here, we investigate the expression, regulation, and functional role of ADAM10 in axonal outgrowth and myelination of the peripheral nerve. Expression pattern analysis of 11 ADAM family members in co‐cultures of rat dorsal root ganglia (DRG) neurons and Schwann cells (SCs) demonstrated the most pronounced mRNA expression for ADAM10. In further studies, ADAM10 was found to be consistently upregulated in DRG‐SC co‐cultures before the induction of myelination. Neurons as well as SCs widely expressed ADAM10 at the protein level. In neurons, the expression of ADAM10 was exclusively limited to the axons before the induction of myelination. Inhibition of ADAM10 activity by the hydroxamate‐based inhibitors GI254023X and GW280264X resulted in a significant decrease in the mean axonal length. These data suggest that ADAM10 represents a prerequisite for myelination, although its activity is not required during the process of myelination itself as demonstrated by expression analysis of myelin protein zero (P0) and Sudan black staining. Hence, during the process of myelin formation, ADAM10 is highly upregulated and appears to be critically involved in axonal outgrowth that is a requirement for myelination in the peripheral nerve. © 2009 Wiley‐Liss, Inc.     

Development and evaluation of a case group concept for inpatients with mental disorders in Germany: Using self-report and expert-rated instruments

The aim of this study was to evaluate a case-mix system to classify inpatients with mental disorders in Germany by means of self-report and expert-rated instruments. The use of case-mix systems enhances the transparency of performance and cost structure and can thus improve the quality of mental health care. We analysed a consecutive sample of 1677 inpatients with mental disorders from 11 hospitals using regression tree analysis. The model assigns patients to 17 groups, accounting for 17% of the variance for duration of stay. Patients with eating disorders had a longer duration of stay than patients with anxiety disorder, duration of mental illness of less than 3–5 years, lower levels of interpersonal problems and higher occupational position. The results showed that besides diagnosis, variables such as duration of illness and interpersonal problems are important for classifying inpatients with mental disorders. The results of the study should be critically reviewed regarding the empirical results of other studies and the appropriateness of case group concepts for inpatients with mental disorders.     

Differential Regulation of RGS-2 by Constant and Oscillating PTH Concentrations

PTH has diverse effects on bone metabolism: anabolic when given intermittently, catabolic when given continuously. The cellular mechanisms underlying the varying target cell response are not clear yet. PTH induces RGS-2, a member of the Regulator of G-protein Signaling protein family, via cAMP/PKA, and inactivates PKC-mediated signaling. To investigate intracellular signaling pathways with different PTH concentration-time patterns, we treated UMR 106-01 osteoblast-like cells in a perfusion system. PTH was administered intermittently (4 min/h, 10⁻⁷ M) or continuously at an equivalent cumulative dose (6.6 × 10⁻⁹ M). cAMP was measured using radioimmunoassay, mRNA levels using real-time rtPCR and ribonuclease protection assay, and protein levels using Western immunoblotting. A single PTH pulse transiently increased cAMP levels by 2000% ± 1200%. In contrast to continuous PTH exposure, cAMP induction remained unchanged with intermittent PTH, ruling out desensitization of the PTH receptor. In continuously perfused cells, RGS-2 abundance was three to five times higher than in cells intermittently exposed to PTH for up to 12 h. MKP-1 and -3 were significantly less induced with pulsatile PTH; exposure-mode-dependent differences in MMP-13 and IGFBP-5 were small. Pulsatile but not continuous PTH administration prevents PTHrP receptor desensitization and accumulation of RGS-2 in osteoblasts, which should preserve PKC-dependent signaling.     

Functioning and disability 6–15 years after traumatic brain injuries in northern Sweden

Objectives –  To assess long‐term functioning and disability after traumatic brain injury (TBI). Material and methods –  Individuals (n = 88) in Norrbotten, northern Sweden, who had been transferred for neurosurgical care were assessed with internationally established TBI outcome measures 6–15 years post‐injury. Results –  There was an improvement in overall outcome from discharge from inpatient rehabilitation to follow‐up. Many individuals had a high degree of motor and cognitive functioning, which enabled them to live independently in their own home without assistance, but there remained a disability related to community reintegration and social participation. This affected their productivity and to some degree their marital stability. The remaining disability and reduced productivity were related to the age at injury and the injury severity. Conclusions –  Our data showed that individuals with a TBI can achieve and maintain a high degree of functioning many years after the injury. Increasing age and a greater injury severity contributed to their long‐term disability.     

小肠浆肌膜腔内自体脾组织移植动物模型的建立与意义

目的探讨增加自体脾组织移植量的方法,提高自体移植脾组织的功能。方法贵州小型香猪3头,经肌注麻醉后剖腹切除脾脏,取脾脏的1/2约150g,切成1mm×1mm×1mm小块备用。在距Treitz韧带50cm处,切取保留肠系膜血管的空肠30cm旷置,再吻合肠管恢复肠腔通道,缝闭肠系膜裂口。旷置空肠等分2段,去除肠粘膜,缝闭一端,将约50g脾组织块分别植于2段肠浆肌膜腔内,缝闭另一端口,妥善固定于肠系膜上。大网膜内移植30g脾组织作为对照观察。结果4个月饲养期间内无肠梗阻发。3段肠浆肌膜腔内脾组织再生良好,组织结构与大网膜内移植脾组织无明显差别,2段再生较差,1段形成脓肿。结论肠浆肌膜腔内移植脾组织的量较大,可作为自体脾组织的移植术式。     

Auriculo-ventricular block and distal myopathy with rimmed vacuoles and desmin storage.

A young patient had an auriculo-ventricular block and a distal myopathy with muscle biopsy findings suggestive of inclusion body myositis. What was most unusual was the presence of numerous sarcoplasmic bodies identified as desmin by electron microscopy and immunocytochemistry. The nosological situation of this condition is discussed.     

Early Intestinal Changes Following Abdominal Radiotherapy

PURPOSE: To compare tests for intestinal function with clinical scores after abdominal irradiation. PATIENTS AND METHODS: At the Department of Radiotherapy, Erfurt, Germany, intestinal changes were studied in 91 patients receiving abdominal radiotherapy between 1992 and 1996. Conventional fractionation (1.8-2 Gy per fraction, total doses 30.6-62.5 Gy) was applied. Before and at weekly intervals during radiotherapy, the clinical response was scored according to RTOG/EORTC for the upper and lower gastrointestinal (GI) tract. Resorption tests for vitamin B(12) and D-xylose were performed before the onset and immediately after treatment. RESULTS: The clinical response displayed a well-defined dose-effect relationship with grade 1 effects in 5% and 50% of the patients at about 10 Gy and 50 Gy, respectively. For grade 2 reactions, 5%- and 50%-effective doses were 20-30 Gy and 60-80 Gy. Effects in the upper and lower GI tract were highly correlated. Changes in body weight did not show a correlation with other clinical symptoms. Changes in resorption also displayed a significant dose effect. However, no correlation was found with the clinical symptoms in the individual patient. CONCLUSION: In the present study, the clinical manifestation of intestinal side effects according to RTOG/EORTC criteria was reflected by neither the vitamin B(12) nor by the D-xylose resorption test. Hence, these tests cannot be regarded as useful for objective quantitation of intestinal radiation injury.     

Complications of temporomandibular joint arthroscopy: a retrospective analytic study of 670 arthroscopic procedures.

PURPOSE: Temporomandibular joint (TMJ) arthroscopy has been considered a safe surgical procedure in the treatment of TMJ derangement. However, it is not exempt from complications. This study evaluates the complications of arthroscopy in patients with internal derangement of TMJ. PATIENTS AND METHODS: Five hundred consecutive patients (670 joints) with TMJ derangement who underwent arthroscopy between 1995 and 2004 were retrospectively analyzed. All the patients were classified as II to V in the Wilkes classification. Lysis and lavage, electrocautery of the posterior ligament, injection of corticoids, injection of ethanolamine, myotomy of lateral pterygoid muscle attachments, myotomy and electrocautery, motor debridement, injection of sodium hyaluronate, and meniscal suture were performed in different patients. RESULTS: Complications were recognized during or immediately after the surgery. They were observed in 5 of 341 (1.26%) arthroscopies of the right TMJ and 4 of 329 (1.21%) arthroscopies of the left TMJ. A 1.34% complication rate was found in the whole series. No blood clots within the external auditory canal were observed. Bleeding within the superior TMJ space was observed in 57 cases (8.5%), 36 of them in the right TMJ and 21 in the left TMJ, but they were not considered as true complications. Lacerations of the external auditory canal were found in 2 cases (0.3%), with no cases of perforation of the tympanic membrane. Lesion of the auriculotemporal nerve was observed in a case. Paresia of the facial nerve was found in 4 cases (0.6%). Alteration of visual accuracy of the ipsilateral eye was also observed in a patient immediately after the surgery. CONCLUSION: Special care must be taken to reduce complications within the upper joint space by means of an adequate instrumentation and by paying attention to essential points of the arthroscopic technique.