Factors predicting tracer uptake in somatostatin receptor and MIBG scintigraphy of metastatic gastroenteropancreatic neuroendocrine tumors.

Radiolabeled octreotide analogs (Oct) and metaiodobenzylguanidine (MIBG) offer 2 different approaches for imaging and targeting metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NET). Despite successful establishment of the revised World Health Organization (WHO) classification, which distinguishes between low- and high-grade malignant GEP-NET, there is a lack of scintigraphic studies comparing uptake behavior on the basis of this categorization. This study aims to define predisposing factors of tracer uptake for both imaging principles implementing the updated tumor criteria of the current WHO classification. METHODS: Fifty-seven consecutive patients with histologically confirmed metastatic GEP-NET evaluated with both 111In-pentetreotide and 123I/131I-MIBG scintigraphy were included in this study. Intensity of tracer uptake was graded according to the different metastatic regions. Patients were classified as overall positive when avid uptake in the clinically relevant tumor lesions was present. Correlation was tested between the proportion of positive patients and tumor origin, function, and malignancy. RESULTS: Overall, 52 patients (91.2%) were Oct positive and 28 patients (49.1%) were MIBG positive. The proportion of tracer-positive patients was significantly higher (P < 0.05) in low-grade malignant tumors for both tracers and in functioning as well as in gastroenteral NET for MIBG. Five patients were negative for both tracers. None of the Oct-negative patients proved to be MIBG positive. CONCLUSION: Oct affinity is observed with high frequency throughout the subgroups of metastatic GEP-NET, whereas corresponding MIBG uptake is overall less prevalent and more group dependent. Tumor differentiation significantly impacts both Oct and MIBG uptake, whereas functionality predisposes only for MIBG accumulation. Though clearly inferior to Oct-based radioimaging in most GEP-NET, MIBG achieves a remarkable rate of radioligand accumulation in functioning midgut enterochromaffin cell metastases (>80% of patients positive). These results may have implications for patient management and potentially for selection and performance of targeted therapy.     

Non-invasive Assessment of Coronary Flow Velocity Reserve: A New Method Using Transthoracic Doppler Echocardiography

Coronary flow reserve (CFR) has been used toassess coronary microcirculation and epicardial coro-nary stenoses[1— 3 ] . CFR is defined as the ratio ofcoronary flow under maximal coronary vasodilatationto coronary flow under resting conditions[4 ] .Whenthe cross- sectional area of epicardial coronary arteriesis constant,coronary flow velocity (CFV) ratios areequal to volume flow ratios.The most common method used clinically formeasuring CFVR is intracoronary Doppler flow(ICD) analysis re…     

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.     

Improved Performance of Hip DXA Using a Novel Region of Interest in the Upper Part of the Femoral Neck: In Vitro Study Using Bone Strength as a Standard of Reference

We tested the hypothesis that bone mineral density (BMD) and bone mineral content (BMC) in proximal human femur specimens in the upper neck region of interest (ROI) and femoral neck axis length (FNAL) provide a significantly better prediction of femoral bone strength than standard ROIs in vitro. BMD and BMC were measured in 110 proximal femur specimens using a standard dual-energy X-ray absorptiometry (DXA) scanner. The analysis included a new ROI in the upper neck as well as the standard ROIs. FNAL was obtained from the scan images. The specimens' failure-load was measured in a mechanical loading device, simulating a fall on the greater trochanter. For the standard ROIs, correlations between failure-load and BMD ranged from R2 = 0.64 (shaft ROI) to R2 = 0.70, p < 0.001 (femoral neck). Prediction of strength by BMD did not significantly differ from those of BMC (R2 ranging from 0.65 to 0.75, p < 0.001). In the upper neck ROI, for both BMD and BMC correlations with failure-load were higher (R2 = 0.76 and 0.81, respectively; p < 0.001). A lower, yet still significant, correlation was found between FNAL and bone strength (R2 = 0.23, p < 0.001). Normalization of failure-load with respect to FNAL did not significantly increase the correlations with densitometric measures. This study provides in vitro evidence indicating that among the ROIs of the proximal femur the newly defined upper neck ROI provides the best prediction of bone strength. Only a weak association was observed between failure load and FNAL.     

Activity-dependent Decay of Early LTP Revealed by Dual EPSP Recording in Hippocampal Slices from Young Rats

The early maintenance of long-term potentiation (LTP) was studied in the CA1 region of hippocampal slices from 12- to 18-day-old rats in a low-magnesium solution (0.1 mM). The α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated components of the field excitatory postsynaptic potential were estimated in parallel using early and late measurements of the composite potential. At the normal test stimulus frequency of 0.1 Hz, LTP was seen initially as a predominant increase in the AMPA component, but converted, via a substantial decay of this component and a gradual growth of the NMDA component, into nearly equal changes of the two components. Interrupting the test stimulation for 10 min, changing the test stimulus frequency to 1/60 Hz after LTP induction, or using a test stimulus frequency of 1/60 Hz during the entire experiment significantly reduced the decay of the potentiation of the AMPA component while enhancing the potentiation of the NMDA one. The ratio between the magnitudes of the two excitatory postsynaptic potential (EPSP) components showed a decaying time course that was independent of the manipulations used. Application of the NMDA antagonist D(-)-2-amino-5-phosphonopentanoic acid (50μM) after LTP induction stabilized the LTP of the AMPA component until washout was started. On the other hand, the phosphatase inhibitor okadaic acid (1 μM) resulted in decay of the potentiation of both EPSP components back to around baseline and altered the time course of the ratio between the components. Our results show that the early maintenance of LTP is controlled in an activity-dependent and NMDA-dependent manner. This process accelerates the decay of LTP of both AMPA and NMDA components in parallel, suggesting that it is similar to homosynaptic long-term depression, although it operates at the normal test stimulus frequency. The data support a scenario in which LTP ensues as a selective AMPA receptor modification and subsequently converts to another modification, possibly a presynaptic one.     

Lectin-induced increase in clonogenic growth of haematopoietic progenitor cells

Abstract: The galactoside-specific plant lectin, Viscum album agglutinin (VAA-I) increases cellular parameters of natural host defence. It also binds to a variety of haematopoietic cells, including progenitors. We investigated whether VAA-I has a stimulatory effect on haematopoietic progenitor cells. Peripheral blood progenitor cells from 7 healthy volunteers were cultured in a colony assay with VAA-I plus erythropoietin (EPO) and stem cell factor (SCF). At 50 pg/ml VAA-I induced a significant increase in the cytokine-dependent clonogenic growth (52% in median, p<0.05). In another set of experiments purified CD34+ cells were isolated from the bone marrow aspirate of 4 patients with non-metastatic breast cancer using fluorescence-activated cell sorting. Binding to CD34+ cells was demonstrated by using directly fluorescence-conjugated VAA-I. Co-incubation with d -galactose significantly abrogated this effect. CD34+ cells were cultured in the presence of EPO, SCF, interleukin-3, granulocyte/monocyte colony-stimulating factor and granulocyte colony-stimulating factor. VAA-I alone had no measurable effect on the clonogenic growth of the isolated cells. However, at concentrations of 100 and 250 pg/ml VAA-I increased the cytokine-dependent proliferation and differentiation of CD34+ cells by a median of 75 and 85%, respectively. The results show that VAA-I binds to haematopoietic progenitor cells and has a co-stimulatory effect on their proliferation.     

Zytogenetische Veränderungen des Prostatakarzinoms

Zusammenfassung Entstehung und Progression von Tumoren werden durch Funktionsst?rungen von spezifischen Genen gesteuert. Obwohl das Prostatakarzinom zu den h?ufigsten Tumoren geh?rt, ist über die bei diesem Tumor involvierten Gene wenig bekannt. Zytogenetische und molekulare Untersuchungen haben gezeigt, da? chromosomale Deletionen besonders h?ufig das Y-Chromosom, 7q, 8p, 10q, 13q, 16q und 17p betreffen. Diese Loci dürften für das Prostatakarzinom relevante Tumorsuppressorgene enthalten. H?ufige DNS-Sequenzvermehrungen von Chromosom 7, 8q und 11q deuten auf die Lokalisation von m?glichen Onkogenen hin. Bereits heute bestehen Anhaltspunkte für eine Prognoserelevanz genetischer Ver?nderungen. Der Nachweis von Polysomien in Prim?rtumoren deuten auf eine ungünstige Prognose hin. Eine Amplifikation des Androgenrezeptors spricht für einen Hormontherapie-resistenten Tumor, welcher m?glicherweise besonders gut auf eine totale Androgenblockade ansprechen wird. Die Identifikation der alterierten Gene und die Entschlüsselung ihrer Funktion k?nnte in Zukunft zu deutlich verbesserten Behandlungsstretegien für Patienten mit Prostatakarzinom führten.      

The frozen elephant trunk technique for the treatment of extensive thoracic aortic aneurysms: operative results and follow-up.

OBJECTIVE: The 'frozen' elephant trunk technique allows for single-stage repair of combined aortic arch and descending aortic aneurysms using a 'hybridprosthesis' with a stented and a non-stented end. This report summarizes the operative- and follow-up data (mean follow-up 14 months) with this new treatment. METHODS: Between 09/01 and 4/04, 22 patients (62+/-9 years; 9 female) with different aortic pathologies (15 aortic dissections, 7 aneurysms) were operated on after approval from the local institutional review board. The stented end of the hybridprosthesis was deployed in the descending aorta through the opened aortic arch during hypothermic circulatory arrest and selective antegrade cerebral perfusion. RESULTS: All patients survived the procedure but one patient died of acute hemorrhage due to rupture of the false lumen in the descending aorta on the second postoperative day. Two patients required reexploration of the chest for bleeding complications. In 2 of 4 patients who developed neurological dysfunction, symptoms resolved completely. In one of them, the descending aorta was perforated intraoperatively due to misplacement of the stented end of the hybridprosthesis. In all follow-up CT-scans thrombus formation in the descending aortic aneurysm excluded by the stented end of the hybridprosthesis has been observed. CONCLUSIONS: This procedure is performed through median sternotomy and combines the concepts of the elephant trunk operation and endovascular stenting of descending aortic aneurysms. Favourable intraoperative and postoperative results during follow-up with regard to thrombus formation around the stented descending aortic segment encourage us to evaluate all patients with thoracic aneurysms extending to proximal and distal of the left subclavian artery for this treatment.