Detection of the Arg702Trp, Gly908Arg and Leu1007fsinsC polymorphisms of the NOD2/CARD15 gene by real-time PCR with melting curve analysis.

Crohn's disease is a complex disorder, with multiple genetic traits. A frameshift mutation (Leu1007fsinsC) and two missense mutations (Gly908Arg and Arg702Trp) in the NOD2/CARD15 gene are strongly associated with susceptibility to Crohn's disease. The presence of one of these risk alleles confers a 2- to 4-fold increase in the risk of developing Crohn's disease, and the presence of two mutant alleles increases the risk over 20-fold. To facilitate the analysis of these polymorphisms, we developed three LightCycler assays to detect the missense mutations Arg702Trp and Gly908Arg and the frameshift mutation Leu100fsinsC in the NOD2/ CARD15 gene. All three assays can be run simultaneously on one LightCycler using identical cycling parameters. Analysis of 53 DNAs from Crohn's patients helped to identify carriers at allele frequencies similar to other Caucasian populations. The sequencing of such DNAs confirmed the accuracy of the assays. In conclusion, we present three rapid and robust assays to detect the Arg702Trp, the Gly908Arg and the Leu1007fsinsC ins mutations in the NOD2/CARD15 gene [corrected]     

Recurrent locking of knee joint caused by intraarticular migration of bioabsorbable tibial interference screw after arthroscopic ACL reconstruction

Two cases are reported in which, after ACL reconstruction with autologous hamstring grafts, tibial polylactide interference screws migrated into the knee joint. Clinically, both patients presented with recurrent locking of the joint. In one case, a broken 15 mm-long tip of the screw was found intra-articularly. In the other case, the whole screw had migrated into the joint cavity. The degradation process of polylactic acid, operative technique and bone quality are discussed as possible reasons for these complications.     

Die Intensivierung der gerichtlichen Kontrolle des Einheitlichen Bewertungsmaßstabs und das Ende der Praxisbudgets

Ohne Zusammenfassung     

Kammerflimmern bei einem 27-j?hrigen Patienten mit Contusio cordis

Zusammenfassung Hintergrund: Bei Patienten mit stumpfem Thoraxtrauma muss mit einer Contusio cordis gerechnet werden. Das Spektrum der Symptomatik variiert von einer leichten regionalen myokardialen Funktionsstörung bis hin zur Ruptur und zum plötzlichen Herztod. Fallbeschreibung: Ein 27-jähriger Patient wurde nach einem Fußtritt gegen die Brust bei Kammerflimmern reanimiert. Das EKG sowie das Enzymmuster entsprachen denen eines akuten Myokardinfarkts, echokardiographisch zeigte sich eine Hypokinesie apikal und anteroseptal bei mittelgradig reduzierter Pumpfuktion. Die 10 Tage nach dem Trauma durchgeführte Koronarangiographie und Lävokardiographie ergaben einen unauffälligen Befund. Schlussfolgerung: Als Ursache des primären Kammerflimmerns und der initialen elektro- und echokardiographischen Befunde muss aufgrund der Anamnese eine Contusio cordis diskutiert und in der Therapie berücksichtigt werden. Abstract Background: Patients with a blunt chest trauma often sustain myocardial contusion. The spectrum of symptoms varies from regional myocardial dysfunction to myocardial rupture of sudden cardiac death. Case Report: After a kick against his chest, a 27-year-old patient was resuscitated because of ventricular fibrillation. ECG and enzymatic pattern corresponded to an acute myocardial infarction, the echocardiogram revealed an apical and anteroseptal hypokinesia. 10 days after the acute event, coronary arteriography and ventriculography did not show any abnormalities. Conclusion: On the basis of the anamnesis, a myocardial contusion must be discussed as reason for the ventricular fibrillation and the pathologic findings in ECG and echocardiogram. This has to be considered in the therapy.     

Adeno-associated virus vector-mediated systemic delivery of IFN-beta combined with low-dose cyclophosphamide affects tumor regression in murine neuroblastoma models.

PURPOSE: Type I IFNs (IFN-alpha/beta) have shown significant antitumor activity in preclinical models but limited efficacy and significant toxicity in clinical trials. We hypothesized that the antitumor activity of type I IFNs could be enhanced by chronic, low-dose systemic delivery and sought to test this in murine neuroblastoma models. EXPERIMENTAL DESIGN: Continuous liver-generated expression of human IFN-beta (hINF-beta) was achieved through a gene therapy-mediated approach using adeno-associated virus vectors encoding hIFN-beta (AAV hINF-beta). Orthotopic localized retroperitoneal and disseminated models of neuroblastoma were established using three different xenografts. Immunohistochemical analysis and ELISA were used to evaluate the antiangiogenic effect of therapy. RESULTS: The development of both localized orthotopic (retroperitoneal) and disseminated neuroblastoma was prevented in all mice expressing hINF-beta. Continued growth of established retroperitoneal tumors, treated with AAV hINF-beta as monotherapy, was significantly restricted, and survival for mice with established, disseminated disease was significantly prolonged following administration of AAV hINF-beta. Analysis of treated tumors revealed a significant antiangiogenic effect. Mean intratumoral vessel density was diminished and expression of the angiogenic factors vascular endothelial growth factor and basic fibroblast growth factor were both decreased. Finally, combination therapy in which AAV hIFN-beta was used together with low-dose cyclophosphamide resulted in regression of both established retroperitoneal and disseminated disease. CONCLUSIONS: AAV-mediated delivery of hIFN-beta when used as monotherapy was able to restrict neuroblastoma growth due in part to inhibition of angiogenesis. When used in combination with conventional chemotherapy, AAV hIFN-beta was able to effect complete tumor regression.     

Image analysis of DNA cytometry for assessing prognosis after resection of esophageal cancer]

Esophagus cancer is a heterogeneous disease with considerable differences in malignant behaviour. Some relevant factors for prognosis are known. In this study we analyzed DNA-ploidy as a potential prognostic parameter in esophagus carcinoma. Paraffin embedded histological material from 50 patients with an esophagus cancer, obtained by resection, were selected for analysis. Tumor areas within the paraffin material were identified by HE-stained reference sections. One 50 microns section was dewaxed, rehydrated and mechanically and enzymatically treated to a suspension of 10,000 cells/ml. 1 ml of the suspension, containing bare nuclei with small rests of cytoplasma was centrifuged on glass slides. The fixed nuclei were air-dried and stained by Feulgen-SITS technique, which allows quantitative measurement of DNA. The DNA analysis was carried out with a computer-controlled single cell cytophotometry (Leytas 2, Leitz, Wetzlar). In contrast to the flow cytometry with image cytometry only tumors cells were measured. Overlapping nuclei, dirt and other artefacts as well as inflammatory cells were efficiently eliminated. With the DNA image cytometry we could differentiate between diploid and hypotriploid, hypertriploid aneuploid tumors. Best prognosis had diploid and hypotriploid tumors, the worst hypertriploid carcinomas. In the multivariate analysis the DNA-content of the tumor cells in esophagus cancer was the only prognostic parameter. DNA-content of tumor cells may become considerably clinical relevant in esophagus cancer for the decision to perform a resection or palliative treatment. In patients with hypertriploid tumors an adjuvant oncological therapy may increase the prognosis.     

DSA—Control of implanted devices for arterial hepatic perfusion

In contrast to conventional film angiography, the perfusion pattern of hepatic arterial chemotherapy was consistently visualized by DSA in 40 patients with implanted Infusaid pump or Port-A devices. Incomplete perfusion of a liver region by the cytotoxic agent was recognized by DSA as accurately as by nuclide scintigraphy. Furthermore, DSA appeared to be more sensitive in determining aberrantly perfused extrahepatic regions; this was especially true when there was a nonligated right hepatic artery. Specific details of vascular lesions and associated complicating events also could be satisfactorily analyzed by DSA only.