Evaluation of aspiration cytology of the liver space occupying lesions by simultaneous examination of smears and cell blocks

This study was undertaken to compare the efficacy of cytologic smears and histological sections from cell blocks in diagnosis of space occupying lesions (SOLs) of the liver and to classify the lesions on the basis of combined cytohistologic diagnosis. The study was conducted on 50 patients who had radiologically detected SOL/SOLs in the liver and ultrasound‐guided fine needle aspiration of liver was done. In all the cases, both smears and cell blocks were made. Forty‐seven cases were diagnosed as malignant and three as benign on both cytologic smears and cell blocks. Hepatocellular carcinoma was diagnosed in 8 (16%) cases and metastasis in 39 (78%) cases. The subtyping of malignancy could not be done on 11 (22%) cytologic smears and 8 (16%) cell block sections. However, on combined cytohistologic correlation, 17 (34%) out of these 19 (38%) cases could be subtyped. Sensitivity of cytologic smears and cell blocks in subtyping of malignancy was 72.3% and 82.9%, respectively. Combined cytohistologic diagnosis was found to be significantly better than isolated cytologic and cell block diagnosis (P ≤ 0.05). To conclude, FNA of the SOLs of the liver is an effective procedure for diagnosing malignancy. However, cytological examination alone may fail to pinpoint the type of the tumor. Concomitant examination of cell block not only confirms the malignancy but also helps in subtyping it. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Diffusion tensor imaging in mild cognitive impairment and Alzheimer's disease: a review

PURPOSE OF REVIEW: To provide a comprehensive review of diffusion tensor imaging in evaluating microstructural changes in the spectrum of cognitive decline from ageing to Alzheimer's disease, in particular focusing on mild cognitive impairment. RECENT FINDINGS: Mild cognitive impairment represents a transition phase between normal ageing and early Alzheimer's disease. Diffusion tensor imaging has emerged as a useful imaging modality that provides information about the structural integrity of tissue. In healthy ageing, diffusion tensor imaging abnormalities occur in the frontal regions, specifically the frontal white matter, anterior cingulum and the genu of the corpus callosum. Some studies report an anterior-posterior gradient change with greater abnormalities in the genu than the splenium of the corpus callosum and in the frontal than parietal white matter. In Alzheimer's disease, diffusion tensor imaging abnormalities are concentrated in the posterior regions: the parahippocampal gyrus, temporal white matter, splenium of corpus callosum and posterior cingulum. In mild cognitive impairment, changes seem to parallel those in Alzheimer's disease, with similar posterior regions showing abnormalities. SUMMARY: Due to the similarities in diffusion tensor imaging findings in both mild cognitive impairment and Alzheimer's disease, it is likely that diffusion tensor imaging has the potential to emerge as a useful clinical tool for early detection and monitoring of disease progression and treatment response in mild cognitive impairment/Alzheimer's disease patients.     

Treatment-resistant depression: critique of current approaches

The aim of the present study was to critically appraise current conceptual approaches; demographic, neurobiological and clinical correlates; and management strategies of treatment-resistant depression (TRD), especially in light of recent research findings. To this end, a review of the relevant English-language literature was undertaken using Medline, Embase and Psychinfo. TRD has been defined in conceptually restrictive terms as symptomatic non-response to physical therapies alone, with little systematic study of aetiology made. It is likely that a range of sociodemographic (such as higher socioeconomic status), genetic (such as variation in functional monoamine polymorphisms) and clinical variables (such as signal hyperintensities seen on structural neuroimaging scans) are responsible for non-response in individuals. There is insufficient evidence to suggest that TRD is associated with specific subtypes of depression, physical comorbidity, personality or chronicity. The large-scale Sequenced Treatment Alternatives to Relieve Depression (STAR*D) and other studies have suggested that a structured psychotherapy such as cognitive behaviour therapy may be as effective as medication in initial drug non-responders. Also conventional alternatives such as the use of older antidepressant classes, pharmacological augmentation or electroconvulsive therapy in established cases of TRD are not as effective as traditionally thought. There is insufficient preliminary evidence to make formal recommendations about the use of novel brain stimulation techniques in TRD. TRD should be re-defined as the failure to reach symptomatic and functional remission after adequate treatment with physical and psychological therapies. Treatment resistance may be more usefully conceived within the context of well-defined cohorts such as patients with specific subtypes of depression. Although neurobiological markers such as gene polymorphisms, which are potentially predictive of medication tolerance and efficacy, may be used in the future, it is likely that sociocultural variables such as beliefs about depression, and evidence-based treatments for it, will also determine treatment resistance.     

White matter hyperintensities in mid-adult life

PURPOSE OF REVIEW: White matter hyperintensities on T2-weighted magnetic resonance imaging are frequent incidental findings in the brains of elderly individuals. Recent studies have reported that they may also be common in middle-aged individuals, and their systematic evaluation in younger populations is necessary. RECENT FINDINGS: Incidental white matter hyperintensities are common in brains of healthy individuals in their 60s and may be seen as early as the 30s and 40s. They are associated with subtle functional impairment and higher prevalence of neuropsychiatric disorders. While cerebrovascular risk factors such as hypertension, diabetes, high homocysteine, and so forth, are known risk factors for white matter hyperintensities, a significant proportion of the variance is unexplained. Genetic factors, alone or in interaction with environmental factors, appear to be important. There is a slight excess of white matter hyperintensities in women, the basis for which is not understood. Longitudinal studies show that those with baseline lesions have a greater progression over time. SUMMARY: New imaging techniques present an opportunity to examine white matter pathology in great detail in younger populations. Standardized methods to examine such pathology and its determinants will help inform strategies for their prevention, which is an important component of a healthy ageing agenda.     

Potentiation of kinesin spindle protein inhibitor-induced cell death by modulation of mitochondrial and death receptor apoptotic pathways

Targeting the mitotic motor kinesin kinesin spindle protein (KSP) is a new strategy for cancer therapy. We have examined the molecular events induced by KSP inhibition and explored possible mechanisms of resistance and sensitization of tumor cells to KSP inhibitors. We found that KSP inhibition induced cell death primarily via activation of the mitochondrial death pathway. In HeLa cells, inhibition of KSP by small-molecule inhibitor monastrol resulted in mitotic arrest and rapid caspase activation. BclXL phosphorylation and loss of mitochondrial membrane potential was detected before significant caspase activation, which was required to trigger the subsequent apoptotic pathway. In A549 cells, however, KSP inhibition did not induce mitochondrial damage, significant caspase activity, or cell death. A549 cells aberrantly exited mitosis, following a prolonged drug-induced arrest, and arrested in a G(1)-like state with 4N DNA content in a p53-dependent manner. Overexpression of BclXL provided a protective mechanism, and its depletion rescued the apoptotic response to monastrol. In addition, Fas receptor was up-regulated in A549 cells in response to monastrol. Treatment with Fas receptor agonists sensitized the cells to monastrol-induced cell death, following exit from mitosis. Thus, activation of the death receptor pathway offered another mechanism to enhance KSP inhibitor-induced apoptosis. This study has elucidated cellular responses induced by KSP inhibitors, and the results provide insights for a more effective cancer treatment with these agents.     

Risk Factors for Transfusion Transmissible Infections Elicited on Post Donation Counselling in Blood Donors: Need to Strengthen Pre-donation Counselling

Donor notification and counselling transforms the legal and ethical requirement of disclosure of transfusion transmissible infection (TTI) in a blood donor into practice. The present study was done to assess the response to the disclosure of TTI reactivity results in blood donors, assess the risk factors in blood donors and follow the compliance of the disclosure and clinical referral in a population of blood donors who are difficult to convince that they may be harbouring infections apparently in a healthy state today but with possible clinical disease consequences in the future. A retrospective study was conducted from April 2011 to November 2012. Screening was done using third generation ELISA kits used according to the manufacturer’s directions; these kits were approved for use in blood banks by the Drug Controller General of India. Those testing repeat reactive were referred for further confirmation and management. The total number of TTI reactive donors was 787 (0.93 %, N = 83,865). The observed response rate in the present study is 21.6 % (167, N = 787). The risk factors for acquiring infections in TTI reactive donors were statistically significant history of high risk behaviour (20.3 %) for human immunodeficiency virus infection and history of jaundice in themselves, family or close contacts (16.1 %) for hepatitis B virus infection. One hundred and ten (65.8 %) of the referred donors were on outpatient clinical care when post-referral follow up was conducted. The study emphasises on continuing sensitization of blood donation camp organisers to the need of privacy during blood donor selection. The study also stresses the need to strengthen the pre-donation counselling at outdoor blood donation at the same time raise awareness amongst blood donors about the importance of post-donation counselling and follow up.