Neuromodulation in Psychiatric disorders: Experimental and Clinical evidence for reward and motivation network Deep Brain Stimulation: Focus on the medial forebrain bundle

Deep brain stimulation (DBS) in psychiatric illnesses has been clinically tested over the past 20 years. The clinical application of DBS to the superolateral branch of the medial forebrain bundle in treatment‐resistant depressed patients—one of several targets under investigation—has shown to be promising in a number of uncontrolled open label trials. However, there are remain numerous questions that need to be investigated to understand and optimize the clinical use of DBS in depression, including, for example, the relationship between the symptoms, the biological substrates/projections and the stimulation itself. In the context of precision and customized medicine, the current paper focuses on clinical and experimental research of medial forebrain bundle DBS in depression or in animal models of depression, demonstrating how clinical and scientific progress can work in tandem to test the therapeutic value and investigate the mechanisms of this experimental treatment. As one of the hypotheses is that depression engenders changes in the reward and motivational networks, the review looks at how stimulation of the medial forebrain bundle impacts the dopaminergic system.     

Association Between Patient and Physician Sex and Physician-Estimated Stroke and Bleeding Risks in Atrial Fibrillation

Background

Physicians treating nonvalvular atrial fibrillation (AF) assess stroke and bleeding risks when deciding on anticoagulation. The agreement between empirical and physician-estimated risks is unclear. Furthermore, the association between patient and physician sex and anticoagulation decision-making is uncertain.

Preparation and evaluation of 99mTc(V)-DMSA complex: studies in medullary carcinoma of thyroid

Consequent to the promising results reported with 99mTc(V)-DMSA for imaging certain types of soft tissue tumors, we have developed methods to prepare this radiopharmaceutical in three ways: from freshly prepared reagents, through the use of a two component kit and use of the standard renal DMSA kit by a modified recipe. The 99mTc(V)-DMSA complex has been subjected to paper electrophoretic and chromatographic procedures and also biodistribution studies. The distinctly different behaviour of this new product compared to that of the well known renal DMSA complex has been clearly established. Scintiimaging in a preliminary clinical trial in patients with medullary carcinoma of the thyroid has been encouraging.     

Noninvasive Electrocardiographic Imaging (ECGI): Application of the Generalized Minimal Residual (GMRes) Method

Electrocardiographic imaging (ECGI) is a developing imaging modality for cardiac electrophysiology and arrhythmias. It reconstructs epicardial potentials, electrograms, and isochrones from electrocardiographic body-surface potentials noninvasively. Current ECGI methodology employs Tikhonov regularization, which imposes constraints on the reconstructed potentials or their derivatives. This approach can sometimes reduce spatial resolution by smoothing the solution. Accuracy depends on a priori knowledge of solution characteristics and determination of an optimal regularization parameter. These properties led us to implement an independent, iterative approach for ECGI—the generalized minimal residual (GMRes) method—which does not apply constraints. GMRes was applied to experimental data during activation/repolarization of normal and infarcted hearts. GMRes reconstructions were compared to Tikhonov reconstructions and to measured gold standards in isolated hearts. Overall, the accuracy of GMRes solutions was similar to Tikhonov regularization. However, in certain cases GMRes recovered localized potential features (e.g., multiple potential minima), which were lost in the Tikhonov solution. Simultaneous use of these two complementary methods in clinical ECGI will ensure reliability and maximal extraction of diagnostic information in the absence of a priori information about a patient's condition.© 2003 Biomedical Engineering Society. PAC2003: 8719Hh, 8757Gg     

Epstein-Barr virus association and ALK gene expression in anaplastic large-cell lymphoma

Anaplastic large cell lymphoma of T/null-cell type (ALCL) is associated with a characteristic genetic abnormality t(2;5) that results in the NPM-ALK chimeric gene and the protein product derived thereof. In 10% to 20% of ALCLs, the translocation partners of the ALK gene are genes other than NPM (variant translocations). ALK gene expression limited to the cytoplasm implies a variant translocation. In this study, we have investigated 46 cases of ALCL for expression and localization of ALK protein and its association with Epstein-Barr virus (EBV) (by hybridization to EBV-encoded nuclear RNA-1 [EBER-1] and immunostaining for LMP-1). ALCL patients with a null cell phenotype were significantly younger as compared with those of T-cell phenotype (mean age: 28 years v 42 years; P =.018). Sixteen of 46 ALCL cases (34%) were ALK positive. ALK-positive patients were significantly younger (mean age: 25 years for those with both cytoplasmic and nuclear staining; 22 years for those with exclusive cytoplasmic staining; and 41 years for those negative for the ALK gene; P =.023). EBER-1 was detected in 9 of 46 cases (20%), and LMP-1 expression was noted in 5 of them. By polymerase chain reaction analysis, all EBV-associated cases that were investigated showed type I EBV. Whereas 2 of 23 T-cell ALCLs (9%) were EBER-1+, and 7 of 23 null-cell ALCLs (30%) showed EBV association (P =.057). EBV association was seen in 20% of ALK-negative cases, in 0% of cases with ALK gene expression in both nucleus and cytoplasm, and in 60% of cases with ALK gene expression exclusively in the cytoplasm (P =.02). Further, although ALK-positive-EBER-1+ cases were LMP-1 negative, ALK-negative-EBER-1+ cases were LMP-1 positive. Our study raises the question whether EBV might have an etiological role in the evolution of ALCLs that lack classical t(2;5).     

A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer.

PURPOSE: Three agents with differing mechanisms of action are available for treatment of advanced colorectal cancer: fluorouracil, irinotecan, and oxaliplatin. In this study, we compared the activity and toxicity of three different two-drug combinations in patients with metastatic colorectal cancer who had not been treated previously for advanced disease. PATIENTS AND METHODS: Patients were concurrently randomly assigned to receive irinotecan and bolus fluorouracil plus leucovorin (IFL, control combination), oxaliplatin and infused fluorouracil plus leucovorin (FOLFOX), or irinotecan and oxaliplatin (IROX). The primary end point was time to progression, with secondary end points of response rate, survival time, and toxicity. RESULTS: A total of 795 patients were randomly assigned between May 1999 and April 2001. A median time to progression of 8.7 months, response rate of 45%, and median survival time of 19.5 months were observed for FOLFOX. These results were significantly superior to those observed for IFL for all end points (6.9 months, 31%, and 15.0 months, respectively) or for IROX (6.5 months, 35%, and 17.4 months, respectively) for time to progression and response. The FOLFOX regimen had significantly lower rates of severe nausea, vomiting, diarrhea, febrile neutropenia, and dehydration. Sensory neuropathy and neutropenia were more common with the regimens containing oxaliplatin. CONCLUSION: The FOLFOX regimen of oxaliplatin and infused fluorouracil plus leucovorin was active and comparatively safe. It should be considered as a standard therapy for patients with advanced colorectal cancer.