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.     

Clinical Application and Histological Examination of the FAMI Screw for Skeletal Anchorage—a Pilot Study*

Maximum anchorage often presents a problem that is difficult to solve during orthodontic tooth movement. Stationary, skeletal anchorage can be achieved in a simple, minimally-invasive manner, and unwanted tooth movements in opposite directions can be prevented by using transmucosally-inserted bone screws.Our initial experience using the FAMI screw as an orthodontic micro-implant proved to be clinically and histologically successful.     

Sensitivity and specificity of a new commercial enzyme-linked immunoassay kit for detecting Entamoeba histolyticaIgG antibodies in serum samples

The study presented here was conducted to evaluate the performance of the newly available RIDASCREEN Set (R-Biopharm AG, Darmstadt, Germany) for the detection of immunoglobulin G antibodies against Entamoeba histolytica. The sensitivity and specificity of this new enzyme-linked immunosorbent assay were evaluated using a panel of sera from 239 individuals. The assay was positive for 43 of 44 patients with invasive amebiasis, including all 18 patients with amebic liver abscess, while it was negative for 190 of 195 adult controls who were either healthy individuals or patients with other parasitic diseases. The kit was found to be highly specific (97.4%) and sensitive (97.7%) for detecting antibodies against E. histolytica in humans. Although antibody titers in patients with amebic liver abscess tend to be higher on average than in patients with invasive amebiasis, it is not possible to distinguish the two forms solely based on the results of this commercial test.     

Magenkarzinom – eine Infektionskrankheit

Gastric cancer still represents the second most common cause of gastrointestinal cancers in Germany. A disturbing issue is that at the time of diagnosis there are less than 15% of patients for whom a cure can be achieved. Nowadays, biological, histomorphological, molecular genetic and epidemiological data suggest that Helicobacter pylori eradication may lead to the prevention of gastric pre-neoplastic lesions and even gastric cancer. At present, eradication can be offered to selected patients and populations at increased risk, but more research is required before embarking on general and global H. pylori eradication for gastric cancer prevention. The main challenge is to determine how long mucosal abnormalities remain reversible and gastric cancer development can be halted.     

Coccygectomy has a favorable effect on the intensity, manifestation, and characteristics of pain caused by coccygodynia: a retrospective evaluation of 34 patients followed for 3–18 years

Background  Coccygodynia can cause severe pain and disability in patients. There are contradictions in the literature regarding the final results of coccygectomy for coccygodynia. We evaluated the long-term effects of coccygectomy on the intensity, characteristics, and manifestation of pain caused by coccygodynia to determine the adequacy of operation among treatment modalities. Materials and methods  Thirty-four patients with coccygodynia were treated by coccygectomy. In 22 cases, trauma, and in one case childbirth was the cause. 11 cases were regarded as idiopathic. The intensity, characteristics of pain, and the most painful activities were evaluated at an average of 7.6 (3–18) years of follow-up time. Results  Before the operation, all 34 patients had pain while sitting, moreover, 26 of them had pain during standing, walking, at night or a combination of these. 21 patients had intolerable or very intensive, mainly acute, sharp or burning pain. 11 patients had dyschesia, 2 had dysuria and 6 had dyspareunia. At follow-up, 7 patients were completely free of pain, 15 others had moderate, 11 medium, and only one patient had severe, but none had intolerable pain. Only seven patients had acute, sharp or burning pain postoperatively. The decrease of average pain score from 8.0 to 3.2 was significant (P < 10⁻¹²). The number of the patients with dyschesia and dyspareunia decreased from 11 to 7 and from 6 to 3, respectively. Two patients had dysuria, but their complaints did not change after the operation. One of the two patients who needed reoperation had an excellent final result, while the other remained unchanged. 12 and 16 patients (together 82%) regarded the final result of the operation excellent and good, respectively. The condition of five others did not change, while one became worse. The patients with younger age, smaller body mass index, and less co-morbidities had better final result. There were no serious complications. Conclusion  Coccygectomy for coccygodynia is a safe method to decrease the intensity of pain and other complaints of the patients. The operation can be the choice of treatment if conservative measures fail.