Severe aortic and arterial aneurysms associated with a TGFBR2 mutation.

BACKGROUND: A 24-year-old man presented with previously diagnosed Marfan\u27s syndrome. Since the age of 9 years, he had undergone eight cardiovascular procedures to treat rapidly progressive aneurysms, dissection and tortuous vascular disease involving the aortic root and arch, the thoracoabdominal aorta, and brachiocephalic, vertebral, internal thoracic and superior mesenteric arteries. Throughout this extensive series of cardiovascular surgical repairs, he recovered without stroke, paraplegia or renal impairment. INVESTIGATIONS: CT scans, arteriogram, genetic mutation screening of transforming growth factor beta receptors 1 and 2. DIAGNOSIS: Diffuse and rapidly progressing vascular disease in a patient who met the diagnostic criteria for Marfan\u27s syndrome, but was later rediagnosed with Loeys-Dietz syndrome. Genetic testing also revealed a de novo mutation in transforming growth factor beta receptor 2. MANAGEMENT: Regular cardiovascular surveillance for aneurysms and dissections, and aggressive surgical treatment of vascular disease

Frequency of Disc Degeneration at Different Levels of Cervical Vertebrae in Adult Patients with Neck Pain on Magnetic Resonance Imaging

Background:Disc degeneration is terminology used for heterogeneous changes affecting the anatomy and physiology of the intervertebral disc. Disc degeneration alters the material properties of the intervertebral disc leading to an unfavorable distribution and transmission of stress to adjacent spinal structures.Objective:The aim of the study was to determine the frequency of disc degeneration at different level of cervical vertebrae in adult patients with neck pain on magnetic resonance imaging.Methodology:In this descriptive study 180 adult patients were included. All patients had been collected from DHQ hospital Gilgit and Ghurki Trust teaching hospital. After informed consent, data were collected through 1.5 tesla GE (closed bore) and 0.35 tesla Hitachi (open bore) MRI machines.Results:Findings show that among 180 adult patients, 136 presented with disc degeneration among which 81 were males and 55 were females. Among 81 males, 63 had disc degeneration at multiple levels while 18 had single disc degeneration. In females 35 patients showed multiple disc degeneration while 20 involved a single disc.Conclusion:It is concluded that disc degeneration is prevalent in males than females. Disc degeneration at multiple levels is higher than single disc degeneration in both genders. Keywords: Disc degeneration, magnetic resonance imaging, intervertebral disc. DOI: 10.7176/JHMN/71-02 Publication date: February 29th 202

Perforated carcinoma of the caecum presenting as necrotising fasciitis of the abdominal wall, the key to early diagnosis and management

BACKGROUND: Necrotising Fasciitis is a life threatening soft tissue infection which requires aggressive, early surgical management. CASE PRESENTATION: We present a rare case of a retroperitoneal perforation of a carcinoma of the caecum presenting as a necrotising fasciitis of the anterior abdominal wall. CONCLUSION: This case highlights the importance of early aggressive debridement to healthy tissue limits, the consideration of a rare underlying cause, and the scope for plastic surgical reconstruction in order that aggressive initial surgery can be adequately performed

Особенности создания и применения электронных учебно-методических изданий в преподавании правовых дисциплин

Материалы II науч.-метод. конф., Гомель, 10–11 нояб. 2011 г

Cross-Priming Dendritic Cells Exacerbate Immunopathology After Ischemic Tissue Damage in the Heart.

BACKGROUND: Ischemic heart disease is a leading cause of heart failure and despite advanced therapeutic options, morbidity and mortality rates remain high. Although acute inflammation in response to myocardial cell death has been extensively studied, subsequent adaptive immune activity and anti-heart autoimmunity may also contribute to the development of heart failure. After ischemic injury to the myocardium, dendritic cells (DC) respond to cardiomyocyte necrosis, present cardiac antigen to T cells, and potentially initiate a persistent autoimmune response against the heart. Cross-priming DC have the ability to activate both CD4 METHODS: We induced type 2 myocardial infarction-like ischemic injury in the heart by treatment with a single high dose of the β-adrenergic agonist isoproterenol. We characterized the DC population in the heart and mediastinal lymph nodes and analyzed long-term cardiac immunopathology and functional decline in wild type and RESULTS: A diverse DC population, including cross-priming DC, is present in the heart and activated after ischemic injury. CONCLUSION: Activation of cytotoxic CD

Gene Expression Signature in Peripheral Blood Detects Thoracic Aortic Aneurysm

BACKGROUND: Thoracic aortic aneurysm (TAA) is usually asymptomatic and associated with high mortality. Adverse clinical outcome of TAA is preventable by elective surgical repair; however, identifying at-risk individuals is difficult. We hypothesized that gene expression patterns in peripheral blood cells may correlate with TAA disease status. Our goal was to identify a distinct gene expression signature in peripheral blood that may identify individuals at risk for TAA. METHODS AND FINDINGS: Whole genome gene expression profiles from 94 peripheral blood samples (collected from 58 individuals with TAA and 36 controls) were analyzed. Significance Analysis of Microarray (SAM) identified potential signature genes characterizing TAA vs. normal, ascending vs. descending TAA, and sporadic vs. familial TAA. Using a training set containing 36 TAA patients and 25 controls, a 41-gene classification model was constructed for detecting TAA status and an overall accuracy of 78+/-6% was achieved. Testing this classifier on an independent validation set containing 22 TAA samples and 11 controls yielded an overall classification accuracy of 78%. These 41 classifier genes were further validated by TaqMan real-time PCR assays. Classification based on the TaqMan data replicated the microarray results and achieved 80% classification accuracy on the testing set. CONCLUSIONS: This study identified informative gene expression signatures in peripheral blood cells that can characterize TAA status and subtypes of TAA. Moreover, a 41-gene classifier based on expression signature can identify TAA patients with high accuracy. The transcriptional programs in peripheral blood leading to the identification of these markers also provide insights into the mechanism of development of aortic aneurysms and highlight potential targets for therapeutic intervention. The classifier genes identified in this study, and validated by TaqMan real-time PCR, define a set of promising potential diagnostic markers, setting the stage for a blood-based gene expression test to facilitate early detection of TAA

Generating and repairing genetically programmed DNA breaks during immunoglobulin class switch recombination

Adaptive immune responses require the generation of a diverse repertoire of immunoglobulins (Igs) that can recognize and neutralize a seemingly infinite number of antigens. V(D)J recombination creates the primary Ig repertoire, which subsequently is modified by somatic hypermutation (SHM) and class switch recombination (CSR). SHM promotes Ig affinity maturation whereas CSR alters the effector function of the Ig. Both SHM and CSR require activation-induced cytidine deaminase (AID) to produce dU:dG mismatches in the Ig locus that are transformed into untemplated mutations in variable coding segments during SHM or DNA double-strand breaks (DSBs) in switch regions during CSR. Within the Ig locus, DNA repair pathways are diverted from their canonical role in maintaining genomic integrity to permit AID-directed mutation and deletion of gene coding segments. Recently identified proteins, genes, and regulatory networks have provided new insights into the temporally and spatially coordinated molecular interactions that control the formation and repair of DSBs within the Ig locus. Unravelling the genetic program that allows B cells to selectively alter the Ig coding regions while protecting non-Ig genes from DNA damage advances our understanding of the molecular processes that maintain genomic integrity as well as humoral immunity