Pro-inflammatory cytokines and chemokines initiate multiple prostate cancer biologic pathways of cellular proliferation,heterogeneity and metastasis in a racially diverse population and underlie the genetic/biologic mechanism of racial disparity: Update

Pro-inflammatory cytokine and chemokines genes drive prostate cancer progression and metastasis: molecular mechanism update and the science that underlies racial disparity. comprehensive review article.Isaac J. Powell, S. Chinni, S.S. Reddy, Alexander Zaslavsky, Navnath Gavande Introduction: In 2013 we reported that with the use of bioinformatics and ingenuity pathway network analysis we were able to identify functional driver genes that were differentially expressed among a large population of African American men (AAM) and European American men (EAM). Pro-inflammatory cytokine genes were found to be more interactive and more expressed among AAM and have been found to be functional drivers of aggressive prostate cancer (CaP) and aggressiveness in other solid tumors. We examined these genes and biological pathways initiated by these cytokines in primary CaP tissue.Method We unravel the gene network and identified biologic pathways that impacted activation of the androgen receptor, mesenchymal epithelial transition (invasion) and chemokines associated with metastasis in the CaP tissue from 639 radical prostatectomy specimens.Results Biologic pathways identified by unraveling pro-inflammatory genes from our network, more expressed among AAM compared to EAM, were tumor necrosis factor (TNF), IL1b, IL6, and IL8. IL6 and IL8 are downstream of TNF activity and are known activators of androgen receptor and through mediators promote CaP cell proliferation. TNF and IL1b mediate tumor cell invasiveness through the activation of MMP (matrix metalloproteinase) which down regulates E-Cadherin to initiate epithelial mesenchymal transition which allows cells to become invasive in the microenvironment. Ultimately our network analysis indicates that TNF and IL1b activate CXCR4 receptor on CaP cells, which facilitates metastatic progression reportedly by binding to CXCL12 on lipid rafts and tumor implantation in the bone marrow.Conclusion Our retrospective biologic mechanistic model reveals a set of pro-inflammatory cytokines and chemokines that drive CaP aggressiveness, tumor heterogeneity, progression and metastasis. A prospective multi-institutional study needs to be conducted for clinical validation as well consideration of targeted therapy.     

Safety and effectiveness of REALIZE adjustable gastric band: 5-year prospective study

BackgroundThe long-term safety results of the REALIZE (Ethicon Endo-Surgery, Inc., Cincinnati, OH) adjustable gastric band collected in this prospective, multicenter study in patients with morbid obesity are presented.ObjectivesTo determine the reoperation rate, including band revisions, replacements, and explants, resulting from a serious adverse device-related event through years 4 and 5. Various efficacy measures were also assessed as secondary objectives.SettingNine academic and/or private institutions.MethodsThe participating institutions enrolled 303 patients, who were then assessed on an annual basis, with 231 patients completing 5 years of follow-up. The study parameters included reoperation rates, changes in percentage of excess weight loss (%EWL), and changes in body mass index (BMI), as well as parameters of diabetes and dyslipidemia. Quality of life was assessed using the Short Form (SF)-36 and the Impact of Weight on Quality of Life-Lite questionnaires.ResultsThe reoperation rate due to a serious adverse event in this population at 5 years after implantation with the REALIZE gastric band was 8.9%. The most common serious adverse event was band slippage, which affected 6.9% of the study population. The mean %EWL was 35.6% ± 26.84%, and the decrease in mean BMI was ?7.01 ± 5.45 kg/m² at 5 years. Patients experienced improvements in mean glycated hemoglobin and serum lipid levels, in addition to improvements in the quality of life measures.ConclusionNo new safety concerns were identified during the 5 years of follow-up. Although the results of this study did not meet the predefined safety criteria of 8% or less, the safety profile and long-term effectiveness observed in this study are consistent with those in the current literature.     

Anhidrotic ectodermal dysplasia presenting as nasal myiasis

An interesting case of anhidrotic Ectoderml Dysplasia (A.E.D.) which came with epistaxix, headache and maggots in nose is presented. Histopathology of forearm shin, scalp and Exercise test helped to confirm the diagnosis, AED is an X-linked recessive condition and has no cure but symptomatic treatment along with heat protection and protection of eyes especially in summer season has a role to play in the management of these cases.     

Antemortem diagnosis of Leigh’s disease: Role of magnetic resonance studies

A two-and-a-half-year-old male child presented with recurrent attacks of intractable vomiting, psychomotor retardation since 14 months of age. He had also lower cranial nerve palsy and corticospinal involvement. Magnetic resonance imaging had shown multiple well circumscribed areas of hypointusity in T, weighted image which were brightly hyperintense in heavily T₂-weighted image. The lesions were seen in basal ganglia, thalamii and brainstenvand spared mamillary bodies. Magnetic resonance spectroscopy demonstrated lactate peak in the affected areas confirming the diagnosis of Leigh’s disease. The child responded well to large dose of vitamin ‘B’, therapy.     

Multiple myeloma presenting as stridor: A case report

Extrame dullary plasmacytoma of larynx is extremely rare. We report a case of multiple myeloma which presented as extrame dullary manifestation in larynx. The rarity of incidence and difficulty in diagnosis of the disease is discussed.     

A Novel Supervised Approach for Segmentation of Lung Parenchyma from Chest CT for Computer-Aided Diagnosis

Segmentation of lung parenchyma from the chest computed tomography is an important task in analysis of chest computed tomography for diagnosis of lung disorders. It is a challenging task especially in the presence of peripherally placed pathology bearing regions. In this work, we propose a segmentation approach to segment lung parenchyma from chest. The first step is to segment the lungs using iterative thresholding followed by morphological operations. If the two lungs are not separated, the lung junction and its neighborhood are identified and local thresholding is applied. The second step is to extract shape features of the two lungs. The third step is to use a multilayer feed forward neural network to determine if the segmented lung parenchyma is complete, based on the extracted features. The final step is to reconstruct the two lungs in case of incomplete segmentation, by exploiting the fact that in majority of the cases, at least one of the two lungs would have been segmented correctly by the first step. Hence, the complete lung is determined based on the shape and region properties and the incomplete lung is reconstructed by applying graphical methods, namely, reflection and translation. The proposed approach has been tested in a computer-aided diagnosis system for diagnosis of lung disorders, namely, bronchiectasis, tuberculosis, and pneumonia. An accuracy of 97.37 % has been achieved by the proposed approach whereas the conventional thresholding approach was unable to detect peripheral pathology-bearing regions. The results obtained prove to be better than that achieved using conventional thresholding and morphological operations.     

New chiral reverse phase HPLC method for enantioselective analysis of ketorolac using chiral AGP column

A simple, specific, precise, sensitive and rapid reverse phase-HPLC method was developed for determination of ketorolac enantiomers, a potent nonnarcotic analgesic in pharmaceutical formulations. The method was developed on a chiral AGP column. Mobile phase was 0.1 M sodium phosphate buffer (pH 4.5): Isopropanol (98:2, v/v), at a flow rate of 1 mL/min with run time of 15 min. Ultraviolet detection was made at 322 nm. The linearity range was 0.02–10 μg/mL for each of the enantiomers. The mobile phase composition was systematically studied to find the optimum chromatographic conditions. Validation of the method under the conditions selected showed that it was selective and precise and that the detector response was linear function of ketorolac.