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.     

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.     

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.     

Entrapment of pacemaker lead by a large netlike Eustachian valve within the right atrium

Summary During pacemaker implantation in a patient with permanent atrial fibrillation, it remained impossible to advance a passive fixation lead with fins through the right atrium. However, a lead with a retractable screw easily passed the right atrium and was positioned in the right ventricle. Transesophageal echocardiography revealed an extensive net–like perforated Eustachian valve within the right atrium that had caused entrapment of the anchor fins during lead implantation. Remnants of embryonal structures within the right atrium should be considered a rare possible barrier during pacemaker implantation.     

Design of clinical trials for chronic diseases: implications for periodontal disease

In order to make effective use of the statistical theory of design of clinical trials for chronic diseases such as periodontal disease, certain issues must be considered. Any clinical trial requires that the disease definition be well-specified; that patient eligibility be explicit; that the observation times be explicit; that the duration and endpoint of therapy be specified; that the duration of subsequent followup observation be specified; and that the unit of observation (e.g., tooth, set of teeth, patient) be defined. In a chronic disease, the potential biases that can readily be introduced by self-selection of patients who enter the trial and/or who return for subsequent observation become more important, because subjects are required to remain on treatment and/or observation for prolonged periods. Further, the cyclical nature of some chronic diseases may require special attention to baseline definitions of active disease and disease outcome. These issues are illustrated with examples from clinical trials of hypertension, breast cancer screening, and Polycythemia Vera. Implications for periodontal disease are discussed.     

Inverse Planning – a Comparative Intersystem and Interpatient Constraint Study

PURPOSE: To compare commercial treatment-planning systems (TPS) for inverse planning (IP) and to assess constraint variations for specific IMRT indications. MATERIAL AND METHODS: For IP, OTP, XiO and BrainSCAN were used and step-and-shoot intensity-modulated radiotherapy (IMRT) delivery was assumed. Based on identical constraints, IP was performed for a prostate, head and neck, brain, and gynecologic case. IMRT plans were compared in terms of conformity/homogeneity, dose-volume histograms (DVHs), and delivery efficiency. For ten patients each of a class of indications, constraint variations were evaluated. RESULTS: IMRT plans were comparable concerning minimum target dose, homogeneity, conformity, and maximum doses to organs at risk. Larger differences were seen in dose gradients outside the target, monitor units, and segment number. Using help structures proved efficient to shape isodoses and to reduce segmentation workload. For IMRT class solutions, IP constraint variations depended on anatomic site. CONCLUSION: IP systems requiring doses as input and having objective functions based on physical parameters had a very similar performance. Constraint templates can be established for a class of IMRT indications.