(18)F-FDG PET/CT in an unusual case of cardiac plexiform neurofibromatosis.

Cardiac involvement is rare in neurofibromatosis 1 (NF 1). Very few cases of cardiac masses in this entity have been documented in the world literature. We present the F-FDG PET/CT findings in a rare case of cardiac plexiform neurofibromatosis.

Traumatic brain injury and the post-concussion syndrome: A diffusion tensor tractography study.

AIM: The aim of the present study is to evaluate diffusion tensor tractography (DTT) as a tool for detecting diffuse axonal injury in patients of acute, mild, and moderate traumatic brain injury (TBI), using two diffusion variables: Fractional anisotropy (FA) and mean diffusivity (MD). The correlation of these indices with the severity of post-concussive symptoms was also assessed. MATERIALS AND METHODS: Nineteen patients with acute, mild, or moderate TBI and twelve age- and sex-matched healthy controls were recruited. Following Magnetic Resonance Imaging (MRI) on a 3.0-T scanner, DTT was performed using the 'fiber assignment by continuous tracking' (FACT) algorithm for fiber reconstruction. Appropriate statistical tools were used to see the difference in FA and MD values between the control and patient groups. In the latter group, the severity of post-concussive symptoms was assessed six months following trauma, using the Rivermead Postconcussion Symptoms Questionnaire (RPSQ). RESULTS: The patients displayed significant reduction in FA compared to the controls (P < 0.05) in several tracts, notably the corpus callosum, fornix, bilateral uncinate fasciculus, and bilateral superior thalamic radiations. Changes in MD were statistically significant in the left uncinate, inferior longitudinal fasciculus, and left posterior thalamic radiation. A strong correlation between these indices and the RPSQ scores was observed in several white matter tracts. CONCLUSION: Diffusion tensor imaging (DTI)-based quantitative analysis in acute, mild, and moderate TBI can identify axonal injury neuropathology, over and above that visualized on conventional MRI scans. Furthermore, the significant correlation observed between FA and MD indices and the severity of post-concussive symptoms could make it a useful predictor of the long-term outcome.

Surface levels of CD20 determine anti-CD20 antibodies mediated cell death in vitro.

BACKGROUND: The sensitivity of human Burkitt's lymphoma cells to rituximab (Rtx) and tositumomab (Tst) was assessed on cells expressing different levels of CD20 on surface. Cells that harbor low CD20 levels may resists against therapeutics response to CD20-specific antibodies. We postulated that, radiation-induced modulation of CD20 surface levels may play a crucial and central role in determining the relative efficacy of rituximab and tositumomab in treating Burkitt's lymphoma disease. Here, we examined the γ-radiation-induced CD20 expression in the Burkitt lymphoma cell line 'Daudi' and the relation of differential levels of CD20 with anti-CD20 mAbs mediated cell death. METHODOLOGY: In this study we examined kinetics of CD20 expression following sub lethal doses ofγ-radiation to Daudi cells and thereafter anti-CD20 mAbs (rituximab and tositumomab) were added in cell suspensions. The correlation of kinetics of CD20 expression and cells treated with anti-CD20 mAbs/or corresponding isotype Abs with special reference to changes in mitochondrial membrane potential and reactive oxygen species generation was also examined. Further, we also investigated the efficacy of anti-CD20 mAbs and possible induction of cell death in relation to levels of CD20 cell surface expression. CONCLUSION: This report provides evidence that CD20 expression can be induced by exposure of cells to γ-radiation. In addition, these findings demonstrated that the efficacy of anti-CD20 mAbs is dependent on the surface levels of CD20. Based on these findings, we hypothesized (i) irradiation just prior to immunotherapy may provide new treatment options even in aggressive B cell tumors, which are resistant to current therapies in vivo (ii) The efficacy of induction of apoptosis varies with type of monoclonal antibodies in vitro.

18F-fluorodeoxyglucose positron emission tomography/computed tomography in a case of non-ketotic hyperglycemia.

Hemichorea and generalized chorea are rare syndromes associated with nonketotic hyperglycemia. This disorder usually afflicts elderly females, and may herald the onset of new onset diabetes, usually type 2. There are conflicting reports of the underlying pathophysiology of this rare entity. Magnetic resonance imaging findings have been described in the past, and are characteristic. There are very few reports of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) findings of this unusual dyskinetic syndrome. This report describes the PET/CT features of this rare disease. Early detection and prompt correction of hyperglycemia may lead to complete or significant amelioration of symptoms.

Connexin-43 regulates p38-mediated cell migration and invasion induced selectively in tumour cells by low doses of γ-radiation in an ERK-1/2-independent manner.

Radiotherapy exposes certain regions of solid tumours to low sublethal doses of γ-radiation that may cause secondary malignancies. Therefore, evaluating low-dose-γ-radiation-induced alterations in tumorigenic potential and understanding their mechanisms could help in improving radiotherapy outcome. Limited studies have indicated connexin (Cx) up-regulation by low doses, whereas Cxs are independently shown to alter cell migration in unirradiated cells. We investigated low-dose-γ-radiation-induced alterations in Cx43 expression and cell proliferation/migration/invasion in various tumour cell lines, along with the putative molecular pathways such as p38 and extracellular signal-regulated kinase-1/2 (ERK-1/2)-mitogen-activated protein kinases (MAPKs). Interestingly, a narrow range of low doses (10-20 cGy) enhanced Cx43 expression and also selectively induced glioma cell migration without altering cell proliferation, accompanied by sustained activation of p38 and up-regulation of p21(waf1/cip1), whereas the lowest (5 cGy) dose induced cell proliferation coupled with enhanced p-ERK1/2, proliferating cell nuclear antigen and p-H3 levels without inducing cell migration. Most importantly, low-dose-γ-radiation-induced cell migration and p38 activation was strongly inhibited by knocking down Cx43 expression, thereby demonstrating latter's upstream role, whereas the knock-down had no effect on ERK-1/2 or cell proliferation. Silencing Cx43 caused near-complete inhibition of radiation-induced cell migration/invasion in all tumour cell lines (U87, BMG-1, A549 and HeLa), whereas no cell migration/invasiveness was induced in the γ-irradiated primary VH10 or transformed AA8 fibroblasts. Our study demonstrates for the first time that low-dose γ-radiation induces p38-MAPK mediated cell migration selectively in tumour cells. Further, this effect is regulated by Cx43, which could thus be an important mediator in radiation-induced secondary malignancies and/or metastasis.

White matter damage is associated with memory decline in chronic alcoholics: a quantitative diffusion tensor tractography study.

Neuroimaging studies have reported an association between white matter integrity and cognitive performance in normal aging and various neuropathological conditions. We compared alcoholics with controls and hypothesized that the degree of disconnection of white matter fibers would be negatively correlated with memory dysfunction scores. Diffusion tensor imaging (DTI) based tractography and PGI-memory scale (PGIMS) test was performed in 10 abstinent chronic alcoholic and 10 demographically equivalent control men. DTI measures [fractional anisotropy (FA), and mean diffusivity (MD)] from all of the major cerebral tracts were calculated and a comparison was done between patient group and controls. Spearman's rank correlation coefficient was computed between memory dysfunction score and DTI measures. Compared to controls alcoholic participants had significantly reduced FA in corpus callosum (CC), fornix (FX), and right hemispheric arcuate fasciculus (AF), anterior thalamic radiation (ATR) and inferior longitudinal fasciculus (ILF). A significant inverse correlation with memory dysfunction score was observed with right cingulum, right uncinate fasciculus, right ILF and left ILF. The inverse correlation of memory dysfunction score with FA of white matter tracts suggest that white matter deficit in these white matter fibers may contribute to underlying dysfunction in memory in alcoholism.

FDG-PET/CT in lymphoma.

Lymphomas are a heterogeneous group of diseases that arise from the constituent cells of the immune system or from their precursors. 18F-fludeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) is now the cornerstone of staging procedures in the state-of-the-art management of Hodgkin's disease and aggressive non-Hodgkin's lymphoma. It plays an important role in staging, restaging, prognostication, planning appropriate treatment strategies, monitoring therapy, and detecting recurrence. However, its role in indolent lymphomas is still unclear and calls for further investigational trials. The protean PET/CT manifestations of lymphoma necessitate a familiarity with the spectrum of imaging findings to enable accurate diagnosis. A meticulous evaluation of PET/CT findings, an understanding of its role in the management of lymphomas, and knowledge of its limitations are mandatory for the optimal utilization of this technique.

Induced pluripotent stem cells: fundamentals and applications of the reprogramming process and its ramifications on regenerative medicine.

OBJECTIVE: To provide a comprehensive source of information about the reprogramming process and induced pluripotency. BACKGROUND: The ability of stem cells to renew their own population and to differentiate into specialized cell types has always attracted researchers looking to exploit this potential for cellular replacement therapies, pharmaceutical testing and studying developmental pathways. While adult stem cell therapy has already been brought to the clinic, embryonic stem cell research has been beset with legal and ethical impediments. FOCUS: The conversion of human somatic cells to human induced pluripotent stem cells (hiPSCs), which are equivalent to human embryonic stem cells (hESCs), provides a system to sidestep these barriers and expedite pluripotent stem cell research for the aforementioned purposes. However, being a very recent discovery, iPSCs have yet to overcome many other obstacles and criticism to be proven safe and feasible for clinical use. METHODOLOGY: This review introduces iPSC, the various methods that have been used to generate them and their pros and cons. It also covers in detail the pluripotency factors responsible for iPSC generation as well as the signaling pathways, epigenetic modifications and miRNA regulation implicated in the reprogramming process. The known molecular crosstalk between these reprogramming regulators is also illuminated. We will also mention the molecular compounds which have been shown to either replace one or more genetic factors or improve overall efficiency and kinetics of iPSC induction. CONCLUSION: To conclude, we will briefly discuss the current problems that hinder bench to bedside translation of iPSC research as well as the possible steps that can bring iPSC therapy and other potential applications closer to fruition.

Prospective evaluation of solitary thyroid nodule on 18F-FDG PET/CT and high-resolution ultrasonography.

PURPOSE: The utility of 18F-FDG PET/CT in the assessment of thyroid nodules is unclear as there are several conflicting reports on the usefulness of SUV as an indicator to distinguish benign from malignant thyroid lesions. This study incorporated an additional parameter, namely dual time point imaging, to determine the diagnostic accuracy of PET/CT imaging. The performance of 18F-FDG PET/CT was compared to that of high-resolution ultrasound which is routinely used for the evaluation of thyroid nodules. METHODS: Two hundred patients with incidentally detected solitary thyroid nodules were included in the study. Each patient underwent ultrasound and PET/CT evaluation within 7 days of each other, reported by an experienced radiologist and nuclear medicine specialist, respectively, in a blinded manner. The PET/CT criteria employed were maximum SUV (SUV(max)) at 60 min and change in SUV(max) at delayed (120 min) imaging. Final diagnosis was based on pathological evaluation and follow-up. RESULTS: Of the 200 patients, 26 had malignant and 174 had benign nodules. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of ultrasound were 80.8, 81.6, 39.6, 96.6 and 81.5%, respectively. Using SUV(max) at 60 min as the diagnostic criterion, the above indices were 80.8, 84.5, 43.8, 96.7 and 84%, respectively, for PET/CT. The SUV(max) of malignant thyroid lesions was significantly higher than benign lesions (16.2 +/- 10.6 vs. 4.5 +/- 3.1, respectively; p = 0.0001). Incorporation of percentage change in SUV(max) at delayed imaging as the diagnostic criterion yielded a slightly improved sensitivity, specificity, PPV, NPV and accuracy of 84.6, 85.6, 46.8, 97.4 and 85.5%, respectively. There was a significant difference in percentage change in SUV(max) between malignant and benign thyroid lesions (14.9 +/- 11.4 vs. -1.6 +/- 13.7, respectively; p = 0.0001). However, there was no statistically significant difference (95% confidence interval) between the diagnostic performance of PET/CT and ultrasound. CONCLUSIONS: Routine use of 18F-FDG PET/CT with SUV(max) at 60 min as the sole diagnostic criterion does not appear to have a significant advantage over high-resolution ultrasound in the evaluation of thyroid nodules. Incorporation of dual time point imaging enhances image interpretation, and yields a higher diagnostic performance, yet it is not statistically significant. Bearing in mind the cost, limited availability and radiation exposure, routine use of 18F-FDG PET/CT for distinguishing benign from malignant thyroid nodules cannot be recommended.