Search

Background: Patients and healthcare stakeholders are increasingly becoming engaged in the planning and conduct of biomedical research. However, limited research characterizes this process or its impact., Objective: We aimed to characterize patient and stakeholder engagement in the 50 Pilot Projects funded by the Patient-Centered Outcomes Research Institute (PCORI), and identify early contributions and lessons learned., Design: A self-report instrument was completed by researchers between 6 and 12 months following project initiation., Participants: Forty-seven principal investigators or their designees (94 % response rate) participated in the study. MAIN MEASURES Self-report of types of stakeholders engaged, stages and levels of engagement, facilitators and barriers to engagement, lessons learned, and contributions from engagement were measured., Key Results: Most (83 %) reported engaging more than one stakeholder in their project. Among those, the most commonly reported groups were patients (90 %), clinicians (87 %), health system representatives (44 %), caregivers (41 %), and advocacy organizations (41 %). Stakeholders were commonly involved in topic solicitation, question development, study design, and data collection. Many projects engaged stakeholders in data analysis, results interpretation, and dissemination. Commonly reported contributions included changes to project methods, outcomes or goals; improvement of measurement tools; and interpretation of qualitative data. Investigators often identified communication and shared leadership strategies as "critically important" facilitators (53 and 44 % respectively); lack of stakeholder time was the most commonly reported challenge (46 %). Most challenges were only partially resolved. Early lessons learned included the importance of continuous and genuine partnerships, strategic selection of stakeholders, and accommodation of stakeholders' practical needs., Conclusions: PCORI Pilot Projects investigators report engaging a variety of stakeholders across many stages of research, with specific changes to their research attributed to engagement. This study identifies early lessons and barriers that should be addressed to facilitate engagement. While this research suggests potential impact of stakeholder engagement, systematic characterization and evaluation of engagement at multiple stages of research is needed to build the evidence base.

The presence of micronuclei (MN) in mammalian cells is related to several mutagenetic stresses. MN are formed as a result of chromosome damage and can be readily identified in exfoliated epithelial cells. MN is chromatin particles derived from acentric chromosomal fragments, which are not incorporated into the daughter nucleus after mitosis. It can be visualized by chromatin stains. A variety of factors influences the formation of MN in cells such as age, sex, genetic constitution, physical and chemical agents, adverse habits such as tobacco, areca nut chewing, smoking, and alcohol consumption. Micronucleation has important implications in the genomic plasticity of tumor cells. The present paper reviews the origin, fate and scoring criteria of MN that serves as a biomarker of exposure to genetic toxins, and for the risk of cancer.

New Findings: What is the central question of this study? Is autonomic dysregulation in a mouse model of muscular dystrophy dependent on left ventricular systolic dysfunction and/or activation of the renin-angiotensin system (RAS) and does it predict development of dilated cardiomyopathy (DCM)? What is the main finding and its importance? The results demonstrate that autonomic dysregulation precedes and predicts left ventricular dysfunction and DCM in sarcoglycan-δ-deficient (Sgcd-/-) mice. The autonomic dysregulation is prevented by treatment of young Sgcd-/- mice with the angiotensin II type 1 receptor blocker losartan. Measurements of RAS activation and autonomic dysregulation may predict risk of DCM, and therapies targeting the RAS and autonomic dysregulation at a young age may slow disease progression in patients. Sarcoglycan mutations cause muscular dystrophy. Patients with muscular dystrophy develop autonomic dysregulation and dilated cardiomyopathy (DCM), but the temporal relationship and mechanism of autonomic dysregulation are not well understood. We hypothesized that activation of the renin-angiotensin system (RAS) causes autonomic dysregulation prior to development of DCM in sarcoglycan-δ-deficient (Sgcd-/-) mice and that the severity of autonomic dysfunction at a young age predicts the severity of DCM at older ages. At 10-12 weeks of age, when left ventricular function assessed by echocardiography remained normal, Sgcd-/- mice exhibited decreases in arterial pressure, locomotor activity, baroreflex sensitivity and cardiovagal tone and increased sympathetic tone compared with age-matched C57BL/6 control mice (P < 0.05). Systemic and skeletal muscle RAS were activated, and angiotensin II type 1 receptor (AT1 R) expression, superoxide and fibrosis were increased in dystrophic skeletal muscle (P < 0.05). Treatment with the AT1 R blocker losartan for 7-9 weeks beginning at 3 weeks of age prevented or strongly attenuated the abnormalities in Sgcd-/- mice (P < 0.05). Repeated assessment of phenotypes between 10 and 75 weeks of age demonstrated worsening of autonomic function, progressive cardiac dysfunction and DCM and increased mortality in Sgcd-/- mice. High sympathetic tone predicted subsequent left ventricular dysfunction. We conclude that activation of the RAS causes severe autonomic dysregulation in young Sgcd-/- mice, which portends a worse long-term prognosis. Therapeutic targeting of the RAS at a young age may improve autonomic function and slow disease progression in muscular dystrophy., (© 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.)

Ameloblastoma is the most common aggressive benign odontogenic tumor of the jaws. Ameloblastoma is a benign epithelial odontogenic tumor that typically arises in the mandible or maxilla or, rarely, in the immediate adjacent soft tissues. A clinical, radiographic and histopathological report is presented of a case of acanthomatous ameloblastoma in relation to molar in the left mandible of a 30-year-old healthy male. The histopathological examination of the removed specimen revealed the histopathological pattern of an acanthomatous ameloblastoma. The radiographic appearance of the lesion showed the presence of multilocular radiolucencies, which were crossing the midline, which is rarely found in ameloblastoma. Due to its rarity and lack of data, we take this opportunity to present a world first case of acanthomatous ameloblastoma which was crossing the midline.

Muscular dystrophies are a group of heterogeneous genetic disorders that cause progressive muscle weakness and wasting, dilated cardiomyopathy and early mortality. There are different types of muscular dystrophies with varying aetiologies but they all have a common hallmark of myofibre degeneration, atrophy and decreased mobility. Mutation in Sgcd (sarcoglycan-δ), a subunit of dystrophin glycoprotein complex, causes LGMD2F (limb girdle muscular dystrophy 2F). Previously, we have reported that Sgcd-deficient (Sgcd-/-) mice exhibit AngII (angiotensin II)-induced autonomic and skeletal muscle dysfunction at a young age, which contributes to onset of dilated cardiomyopathy and mortality at older ages. Two counter-regulatory RAS (renin-angiotensin system) pathways have been identified: deleterious actions of AngII acting on the AT1R (AngII type 1 receptor) compared with the protective actions of Ang-(1-7) [angiotensin-(1-7)] acting on the receptor Mas. We propose that the balance between the AngII/AT1R and Ang-(1-7)/Mas axes is disturbed in Sgcd-/- mice. Control C57BL/6J and Sgcd-/- mice were treated with Ang-(1-7) included in hydroxypropyl β-cyclodextrin (in drinking water) for 8-9 weeks beginning at 3 weeks of age. Ang-(1-7) treatment restored the AngII/AT1R compared with Ang-(1-7)/Mas balance, decreased oxidative stress and fibrosis in skeletal muscle, increased locomotor activity, and prevented autonomic dysfunction without lowering blood pressure in Sgcd-/- mice. Our results suggest that correcting the early autonomic dysregulation by administering Ang-(1-7) or enhancing its endogenous production may provide a novel therapeutic approach in muscular dystrophy.

Aims and Objectives: To determine the association between smoking, chewing tobacco (gutka), and age of individual on graying of hair., Materials and Methods: The present study was conducted on 120 patients attending the Outpatient Department of the DJ College of Dental Sciences and Research, Modinagar, UP. The individuals were classified into four groups (group I, II, III, IV) on the basis of the form of tobacco use (smoking or chewing). The Pearson correlation coefficient was utilized to find the correlation between the mean percentage of individuals with gray hair, risk multiplication factor (RMF), and age of the individual., Results: Mean percentage of individual with gray hair and RMF (r = 0.6487) are found to be positively associated. A significant and positive correlation was observed between the age of the individual and the frequency of individuals with gray hair., Conclusion: This study suggests that there is a significant association between tobacco use and aging on graying of hair.

The concept of field cancerization has been ever changing since its first description by Slaughter et al in 1953. Field cancerization explains the mechanisms by which second primary tumors (SPTs) develop. SPTs are the tumors, which develop in the oral cavity in succession to the primary malignant tumors, which might vary in duration ranging from few months to years. Conceivably, a population of daughter cells with early genetic changes (without histopathology) remains in the organ, demonstrating the concept of field cancerization. This review explains the concept of field cancerization and various field theories along with molecular basis of field formation.

Genetically modified bacterial flagellin (Fla), a Toll-like receptor-5 (TLR5) ligand, was evaluated as a fusion partner for human papillomavirus (HPV) L2-based immunogens in two animal challenge models; either cutaneous inoculation of rabbits with HPV 'quasivirions' containing cottontail rabbit papillomavirus (CRPV) genomes that induce warts, or intra-vaginal inoculation of mice with HPV 'pseudovirions' encapsidating a luciferase reporter plasmid and measurement of bioluminescence to determine infectivity. An Escherichia coli production system was developed for flagellin-L2 (Fla-L2) fusions containing either monomeric HPV-16 L2 a.a. 11(×11-200) or oligomeric L2 comprising a fusion of the a.a. 11-88 peptides of five (Fla∼5×11-88) or eight (Fla∼8×11-88) genital HPV types. Immunogenicity and bioactivity of Fla-L2 constructs were assessed using an in vitro neutralization and cell-based TLR-5 binding assay, respectively. Efficacy was evaluated following active immunization of rabbits or mice administered 3 intramuscular doses of Fla-L2 recombinants without exogenous adjuvant, followed by challenge. In addition, passive immunization studies of naïve rabbits with serial dilutions of pooled immune sera were used to determine End-Point Protection Titers (EPPT) for each formulation against a broader spectrum of HPV quasivirions. Efficacy was assessed for up to 10 weeks on the basis of wart volume induced following challenge and results compared to licensed L1-VLP vaccines (Gardasil and Cervarix). Following active immunization at doses as low as 1 μg, Fla-L2 fusions afforded complete protection against infection (mice) and disease (rabbits) following either homologous or heterologous HPV challenge. Passive immunization with anti-L2 immune sera discriminated between the different vaccine candidates under evaluation, demonstrated the protective role of antibody and suggested the superiority of this oligomeric L2-TLR5 agonist fusion approach compared to L1-based vaccines in its ability to cross-protect against non-vaccine HPV types., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

As health care providers adopt and make "meaningful use" of health information technology (health IT), communities and delivery systems must set up the infrastructure to facilitate health information exchange (HIE) between providers and numerous other stakeholders who have a role in supporting health and care. By facilitating better communication and coordination between providers, HIE has the potential to improve clinical decision-making and continuity of care, while reducing unnecessary use of services. When implemented as part of a broader strategy for health care delivery system and payment reform, HIE capability also can enable the use of analytic tools needed for population health management, patient engagement in care, and continuous learning and improvement. The diverse experiences of seven communities that participated in the three-year federal Beacon Community Program offer practical insight into factors influencing the technical architecture of exchange infrastructure and its role in supporting improved care, reduced cost, and a healthier population. The case studies also document challenges faced by the communities, such as significant time and resources required to harmonize variations in the interpretation of data standards. Findings indicate that their progress developing community-based HIE strategies, while driven by local needs and objectives, is also influenced by broader legal, policy, and market conditions.

New Findings What is the topic of this review? This symposium report summarizes autonomic, cardiac and skeletal muscle abnormalities in sarcoglycan-δ-deficient mice (Sgcd-/-), a mouse model of limb girdle muscular dystrophy, with emphasis on the roles of autonomic dysregulation and activation of the renin-angiotensin system at a young age. What advances does it highlight? The contributions of the autonomic nervous system and the renin-angiotensin system to the pathogenesis of muscular dystrophy are highlighted. Results demonstrate that autonomic dysregulation precedes and predicts later development of cardiac dysfunction in Sgcd-/- mice and that treatment of young Sgcd-/- mice with the angiotensin type 1 receptor antagonist losartan or with angiotensin-(1-7) abrogates the autonomic dysregulation, attenuates skeletal muscle pathology and increases spontaneous locomotor activity. Muscular dystrophies are a heterogeneous group of genetic muscle diseases characterized by muscle weakness and atrophy. Mutations in sarcoglycans and other subunits of the dystrophin-glycoprotein complex cause muscular dystrophy and dilated cardiomyopathy in animals and humans. Aberrant autonomic signalling is recognized in a variety of neuromuscular disorders. We hypothesized that activation of the renin-angiotensin system contributes to skeletal muscle and autonomic dysfunction in mice deficient in the sarcoglycan-δ (Sgcd) gene at a young age and that this early autonomic dysfunction contributes to the later development of left ventricular (LV) dysfunction and increased mortality. We demonstrated that young Sgcd-/- mice exhibit histopathological features of skeletal muscle dystrophy, decreased locomotor activity and severe autonomic dysregulation, but normal LV function. Autonomic regulation continued to deteriorate in Sgcd-/- mice with age and was accompanied by LV dysfunction and dilated cardiomyopathy at older ages. Autonomic dysregulation at a young age predicted later development of LV dysfunction and higher mortality in Sgcd-/- mice. Treatment of Sgcd-/- mice with the angiotensin type 1 receptor blocker losartan for 8-9 weeks, beginning at 3 weeks of age, decreased fibrosis and oxidative stress in skeletal muscle, increased locomotor activity and prevented autonomic dysfunction. Chronic infusion of the counter-regulatory peptide angiotensin-(1-7) resulted in similar protection. We conclude that activation of the renin-angiotensin system, at a young age, contributes to skeletal muscle and autonomic dysfunction in muscular dystrophy. We speculate that the latter is mediated via abnormal sensory nerve and/or cytokine signalling from dystrophic skeletal muscle to the brain and contributes to age-related LV dysfunction, dilated cardiomyopathy, arrhythmias and premature death. Therefore, correcting the early autonomic dysregulation and renin-angiotensin system activation may provide a novel therapeutic approach in muscular dystrophy.

We describe an unusual case of severe combined immunodeficiency (SCID) with neutropenia and central nervous system (CNS) manifestations in which a novel RAG1 mutation was identified. A 15-month-old boy presented with failure to thrive, neutropenia and recurrent infections. He was diagnosed with T-B-NK+ SCID. He subsequently developed right partial seizures with ipsilateral hemiparesis and became comatose. Magnetic resonance imaging (MRI) of the brain revealed an inflammatory lesion in the left thalamus which later progressed to diffuse meningo-encephalitis on serial imaging. No CNS infection was documented. Genetic work-up in the child revealed a novel homozygous deleterious mutation in the RAG1 gene (c:2881T>C; p:I794T), for which both parents were heterozygous. He underwent a haploidentical bone marrow transplant without conditioning and died on day +35 with no improvement in his neurological status. The features of neutropenia and progressive encephalopathy could be linked to the novel genetic defect but more data is required to establish this conclusively., (Copyright © 2013 King Faisal Specialist Centre & Research Hospital. Published by Elsevier B.V. All rights reserved.)

Muscular dystrophy is a progressive disease of muscle weakness, muscle atrophy and cardiac dysfunction. Patients afflicted with muscular dystrophy exhibit autonomic dysfunction along with cognitive impairment, severe depression, sadness, and anxiety. Although the psychological aspects of cardiovascular disorders and stress disorders are well known, the physiological mechanism underlying this relationship is not well understood, particularly in muscular dystrophy. Therefore, the goal of this perspective is to highlight the importance of autonomic dysfunction and psychological stress disorders in the pathogenesis of muscular dystrophy. This article will for the first time-(i) outline autonomic mechanisms that are common to both psychological stress and cardiovascular disorders in muscular dystrophy; (ii) propose therapies that would improve behavioral and autonomic functions in muscular dystrophy.

Regulator of G protein signaling 2 (RGS2) is a GTPase-activating protein for G(q/11)α and G(i/o)α subunits. RGS2 deficiency is linked to hypertension in mice and humans, although causative mechanisms are not understood. Because endothelial dysfunction and increased peripheral resistance are hallmarks of hypertension, determining whether RGS2 regulates microvascular reactivity may reveal mechanisms relevant to cardiovascular disease. Here we have determined the effects of systemic versus endothelium- or vascular smooth muscle-specific deletion of RGS2 on microvascular contraction and relaxation. Contraction and relaxation of mesenteric resistance arteries were analyzed in response to phenylephrine, sodium nitroprusside, or acetylcholine with or without inhibitors of nitric oxide (NO) synthase or K(+) channels that mediate endothelium-derived hyperpolarizing factor (EDHF)-dependent relaxation. The results showed that deleting RGS2 in vascular smooth muscle had minor effects. Systemic or endothelium-specific deletion of RGS2 strikingly inhibited acetylcholine-evoked relaxation. Endothelium-specific deletion of RGS2 had little effect on NO-dependent relaxation but markedly impaired EDHF-dependent relaxation. Acute, inducible deletion of RGS2 in endothelium did not affect blood pressure significantly. Impaired EDHF-mediated vasodilatation was rescued by blocking G(i/o)α activation with pertussis toxin. These findings indicated that systemic or endothelium-specific RGS2 deficiency causes endothelial dysfunction resulting in impaired EDHF-dependent vasodilatation. RGS2 deficiency enables endothelial G(i/o) activity to inhibit EDHF-dependent relaxation, whereas RGS2 sufficiency facilitates EDHF-evoked relaxation by squelching endothelial G(i/o) activity. Mutation or down-regulation of RGS2 in hypertension patients therefore may contribute to endothelial dysfunction and defective EDHF-dependent relaxation. Blunting G(i/o) signaling might improve endothelial function in such patients.

The Beacon Community Cooperative Agreement Program is funding 17 communities to build and strengthen their health information technology (IT) capabilities to enhance care coordination, improve patient and population health, and reduce or restrain costs. Based on the experiences and evidence generated by these communities, the program hopes to illustrate the possibilities of leveraging health IT to achieve desired goals. Doing so requires rigorous evaluation work, which is the subject of this issue brief. Based on semistructured interviews with representatives from each Beacon Community, the brief outlines various study designs, evaluation approaches, outcome measures, and data sources in use. It also identifies some common challenges, including establishing governance models, determining baseline measures, and assessing impact in a relatively constrained timeframe. Technical assistance in disseminating and publishing findings and assessing return on investments will be offered in the coming year.

The consequences of acute hypothermia include impaired cardiovascular performance, ultimately leading to circulatory collapse. We examined the extent to which this results from intrinsic limitations to cardiac performance or physiological dysregulation/autonomic imbalance, and whether chronic cold exposure could ameliorate the impaired function. Wistar rats were held at a 12 h:12 h light:dark (L:D) photoperiod and room temperature (21°C; euthermic controls), or exposed to a simulated onset of winter in an environmental chamber by progressive acclimation to 1 h:23 h L:D and 4°C over 4 weeks. In vivo, acute cold exposure (core temperature, T(b)=25°C) resulted in hypotension (approximately -20%) due to low cardiac output (approximately -30%) accompanying a bradycardia (approximately -50%). Cold acclimation (CA) induced only partial compensation for this challenge, including increased coronary flow at T(b)=37°C (but not at T(b)=25°C), maintenance of ventricular capillarity and altered sympathovagal balance (increased low:high frequency in power spectral analysis, PSA), suggesting physiological responses alone were insufficient to maintain cardiovascular performance. However, PSA showed maintenance of cardiorespiratory coupling on acute cold exposure in both groups. Ex vivo cardiac performance revealed no change in intrinsic heart rate, but a mechanical impairment of cardiac function at low temperatures following CA. While CA involved an increased capacity for β-oxidation, there was a paradoxical reduction in developed pressure as a result of adrenergic down-regulation. These data suggest that integrated plasticity is the key to cardiovascular accommodation of chronic exposure to a cold environment, but with the potential for improvement by intervention, for example with agents such as non-catecholamine inotropes.

The methods used to assess cardiac parasympathetic (cardiovagal) activity and its effects on the heart in both humans and animal models are reviewed. Heart rate (HR)-based methods include measurements of the HR response to blockade of muscarinic cholinergic receptors (parasympathetic tone), beat-to-beat HR variability (HRV) (parasympathetic modulation), rate of post-exercise HR recovery (parasympathetic reactivation), and reflex-mediated changes in HR evoked by activation or inhibition of sensory (afferent) nerves. Sources of excitatory afferent input that increase cardiovagal activity and decrease HR include baroreceptors, chemoreceptors, trigeminal receptors, and subsets of cardiopulmonary receptors with vagal afferents. Sources of inhibitory afferent input include pulmonary stretch receptors with vagal afferents and subsets of visceral and somatic receptors with spinal afferents. The different methods used to assess cardiovagal control of the heart engage different mechanisms, and therefore provide unique and complementary insights into underlying physiology and pathophysiology. In addition, techniques for direct recording of cardiovagal nerve activity in animals; the use of decerebrate and in vitro preparations that avoid confounding effects of anesthesia; cardiovagal control of cardiac conduction, contractility, and refractoriness; and noncholinergic mechanisms are described. Advantages and limitations of the various methods are addressed, and future directions are proposed.

Calcitonin gene-related peptide (CGRP) is a powerful vasodilator that interacts with the autonomic nervous system. A subunit of the CGRP receptor complex, receptor activity-modifying protein 1 (RAMP1), is required for trafficking of the receptor to the cell surface and high-affinity binding to CGRP. We hypothesized that upregulation of RAMP1 would favorably enhance autonomic regulation and attenuate hypertension. Blood pressure, heart rate, and locomotor activity were measured by radiotelemetry in transgenic mice with ubiquitous expression of human RAMP1 (hRAMP1) and littermate controls. Compared with control mice, hRAMP1 mice exhibited similar mean arterial pressure, a lower mean heart rate, increased heart rate variability, reduced blood pressure variability, and increased baroreflex sensitivity (2.83+/-0.20 versus 1.49+/-0.10 ms/mm Hg in controls; P<0.05). In control mice, infusion of angiotensin II (Ang-II) increased mean arterial pressure from 118+/-2 mm Hg to 153+/-4 and 174+/-6 mm Hg after 7 and 14 days of infusion, respectively (P<0.05). In contrast, Ang-II hypertension was markedly attenuated in hRAMP1 mice with corresponding values of mean arterial pressure of 111+/-2, 119+/-2, and 132+/-3 mm Hg. Ang-II induced decreases in baroreflex sensitivity and heart rate variability, and increases in blood pressure variability observed in control mice were also abrogated or reversed in hRAMP1 mice (P<0.05). Moreover, during the Ang-II infusion, the pressor response to the CGRP receptor antagonist CGRP(8-37) was significantly greater (P<0.05) in hRAMP1 mice (+30+/-2 mm Hg) than in control mice (+19+/-2 mm Hg), confirming a significantly greater antihypertensive action of endogenous CGRP in hRAMP1 mice. We conclude that RAMP1 overexpression attenuates Ang-II-induced hypertension and induces a protective change in cardiovascular autonomic regulation.

Arterial baroreceptors provide a neural sensory input that reflexly regulates the autonomic drive of circulation. Our goal was to test the hypothesis that a member of the acid-sensing ion channel (ASIC) subfamily of the DEG/ENaC superfamily is an important determinant of the arterial baroreceptor reflex. We found that aortic baroreceptor neurons in the nodose ganglia and their terminals express ASIC2. Conscious ASIC2 null mice developed hypertension, had exaggerated sympathetic and depressed parasympathetic control of the circulation, and a decreased gain of the baroreflex, all indicative of an impaired baroreceptor reflex. Multiple measures of baroreceptor activity each suggest that mechanosensitivity is diminished in ASIC2 null mice. The results define ASIC2 as an important determinant of autonomic circulatory control and of baroreceptor sensitivity. The genetic disruption of ASIC2 recapitulates the pathological dysautonomia seen in heart failure and hypertension and defines a molecular defect that may be relevant to its development., (2009 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to evaluate the role and detection rate of multidetector spiral CT renal angiography (CTA) as compared with conventional angiography (CA), the commonly accepted gold standard, in the diagnosis of renal artery fibromuscular dysplasia (FMD). In addition, the role of CTA reconstructions (multiplanar reformatted images (MPR), maximum intensity projections (MIP) and shaded-surface display (SSD)) in the detection of FMD was also evaluated., Materials and Methods: CTA results were retrospectively reviewed in 21 hypertensive patients with CA-proven FMD. Clinical indications for referral included resistant hypertension (requiring greater than three antihypertensive medications), labile hypertension, hypertension in combination with renal impairment and the presence of abdominal bruits in the context of systemic hypertension. In some cases, these clinical indications were supplemented by positive results in other tests, including plasma renin assay, captopril scintigraphy and/or Doppler ultrasound. The findings of CA in these 21 patients were compared to CTA., Results: Mean patient age was 62.33+14.32 years (range 24-85 years). CTA identified all 42 main renal arteries (100%) and all 10 accessory renal arteries (100%) visualized on CA. In the diagnosis of FMD, CTA detected all 40 (100%) lesions detected by CA. No single CTA reconstruction technique was able to detect all lesions noted on corresponding CA, however, upon review of all CTA reconstructions (MPR, MIP and SSD) in each case, every lesion was correctly identified by CTA., Conclusion: Our experience suggests that CTA is a non-invasive, reliable and accurate method for the diagnosis of renal artery fibromuscular dysplasia. Moreover, in our experience CTA has many advantages as a diagnostic screening tool over CA, including accessibility, speed, lower complication profile, versatility and cost-effectiveness. CTA shows great potential as a guiding tool for directing subsequent procedures such as CA+balloon angioplasty.

A case of giant renal artery aneurysm in a 63-year-old man is presented. Renal artery aneurysms are rare (incidence of <1%) and this case is one of the largest giant renal artery aneurysms recorded in the literature. This case also demonstrates the value of multidetector spiral CT renal angiography (CTA) in the diagnosis, planning and treatment of renal aneurysms.

Introduction: A pilot study to evaluate helical computer tomography (CT) as a diagnostic tool for acute lower gastrointestinal tract (GIT) bleeding. CT was compared to conventional angiography (CA) and colonoscopy for the diagnosis and detection of bleeding site in suspected cases of acute lower GIT bleeding., Methods: Seven patients presenting with acute lower GIT bleeding, between June and November 2002, underwent CT examinations. All of these seven patients underwent CA following CT. Emergency colonoscopies were performed on five patients investigated with both CT and CA. Median delay from the most recent episode of hematochezia to CT was two and a half hours, to CA was 3h, and to colonoscopy was 4h. None of the patients underwent nuclear medicine (NM) bleeding studies., Results: Haemoglobin drop in all patients was greater than 15 g/L in the first 24h of presentation. The mean age was 68.86 years (range, 49-83 years). Comparing CT and CA, there were four concordant and three discordant results. Both modalities had concordant findings of two active bleeding sites, one non-bleeding rectal tumour, and one negative case result. In three patients, the source of bleeding was found on CT whereas CA was negative. Emergency colonoscopies performed in all of these three patients confirmed blood in the colon/ileum., Conclusion: Early experience suggests that CT is a safe, convenient and accurate diagnostic tool for acute lower GIT haemorrhage. It raises questions regarding the sensitivity of CA. A new management algorithm for acute lower GIT haemorrhage using CT as the pre-CA screening tool is being proposed based on the preliminary findings. Positive CT will allow directed therapeutic angiography, while negative CT will triage patients into alternative management pathways.

Purpose: To evaluate the feasibility, safety, and technical efficacy of image-guided radiofrequency ablation (RFA) for the treatment of small peripheral renal tumors and to report our early results with this treatment modality., Methods: Twenty-two RFA sessions for 18 tumors were performed in 11 patients with renal tumors. Indications included coexistent morbidity, high surgical or anesthetic risk, solitary kidney, and hereditary predisposition to renal cell carcinoma. Ten patients had CT-guided percutaneous RFA performed on an outpatient basis. One patient had open intraoperative ultrasound-guided RFA. Technical success was defined as elimination of areas that enhanced at imaging within the entire tumor. With the exception of one patient with renal insufficiency who required gadolinium-enhanced MRI, the remaining patients underwent contrast-enhanced CT for post-treatment follow-up assessment. Follow-up was performed after 2-4 weeks and then at 3, 6, 12 months, and every 12 months thereafter., Results: Fourteen (78%) of 18 tumors were successfully ablated with one session. Three of the remaining four tumors required two sessions for successful ablation. One tumor will require a third session for areas of persistent enhancement. Mean patient age was 72.82 +/- 10.43 years. Mean tumor size was 1.95 +/- 0.79 cm. Mean follow-up time was 10.91 months. All procedures were performed without any major complications., Conclusions: Our early experience with percutaneous image-guided radiofrequency ablation demonstrates it to be a feasible, safe, noninvasive, and effective treatment of small peripheral renal tumors.

The factors that bind to the hepatic-specific human apolipoprotein AI (apoAI) 48-bp downstream enhancer (DSE) were identified and characterized by electrophoretic mobility shift assays. A significant homology was shown between the histone 4 (H4) promoters and the hepatic-specific human apoAI DSE at Sp1 and H4TF2 binding sites. Human HepG2 nuclear extracts were used to form four specific complexes with the DSE (referred to as apoAI DSE-1, -2, -3, and -4). The apoAI DSE-1 and -2 complexes showed similar binding specificity to the Sp/H4TF1 consensus site within the apoAI DSE. The apoAI DSE-1 complex was predominantly recognized by anti-Sp1 and Sp3 sera in gel shift assays, indicating that the DSE was recognized by multiple Sp family members. Nuclear extracts that were prepared from retinoic acid treated HepG2 cells showed increased levels of Sp factors in gel shift and Western blot assays. The apoAI DSE-2 complex was identified as H4TF1 and formed in the absence of magnesium chloride. The apoAI DSE-3 complex bound to a consensus GATA element within the DSE that was recognized by recombinant human GATA-6 as well. The apoAI DSE-3 complex was completely disrupted by a GATA-4 antibody in EMSA. GATA-4 and -6 were detected in nuclear extracts prepared from retinoic acid treated HepG2 cells using Western blot assays. The highest apoAI DSE-3 levels were observed with retinoic acid treated HepG2 cell nuclear extracts in EMSA. ApoAI DSE-4 is a multi-factor complex that includes an Sp/H4TF1 factor and either H4TF2 or apoAI DSE-3. Because apoAI DSE mutations revealed transcription defects in transient transfection assays, we conclude that the entire DSE sequence is required for full apoAI transcriptional activity in HepG2 cells.

Stroke is a thrombohemorrhagic disorder of the central nervous system, with a fairly good outcome in pediatric age group except for the infancy period. In children ischemic type is more common than hemorrhagic type. Though it is difficult to distinguish between thrombotic and embolic phenomenon but it is largely due to cardiovascular lesions, at times it may be the first symptom to appear. The signs and symptoms also appear to be vague in children, hence difficult to pinpoint the etiology. The treatment of stroke is largely for stabilization of the patient, but it is very important to know the cause to prevent future strokes. Use of heparin in ischemic stroke is very promising and thrombolytic therapy is under trial.

Acute headaches in a child evoke anxiety in parents, of a possible catastrophic underlying intracranial pathology. Headaches constitute up to 2 to 6% of all emergency room visit. The prevalence of migraine is increasing. The majority of children have migraine without aura, and about one fifth have migraine with aura. Complicated migraine presents with dramatic neurologic signs and remains a diagnosis of exclusion. Children with migraine require reassurance, modification of life style and food habits, combined with judicious use of simple abortive medications and antiemetics. Prophylaxis in migraine is recommended for frequent or severe attacks and in complicated migraine.

We report three patients who lapsed into coma and subsequently manifested hypersomnolence, amnesia and vertical gaze paresis. Computed tomography revealed bilateral paramedian thalamic infarcts. This clinical symptomatology comprises the paramedian diencephalic syndrome.

Eight patients with hemiplegic migraine are described. Majority were in their second decade and suffered two or more episodes of dense hemiplegia outlasting the headache. Complete recovery was the rule.

We report a 25 year old male who suffered thalamic and multiple cerebellar infarctions during infrequent attacks of basilar artery migraine. Migraine-related infarcts at these sites are uncommon.

Fifteen patients presenting with visual, oculomotor and behavioural disturbances were diagnosed to be suffering from "top of the basilar" syndrome. Computed tomography confirmed the distribution of infarctions in the vascular territory of the rostral basilar artery. The clinical profile comprised cortical blindness and visual field defects, vertical gaze paresis, memory and behavioural disturbances and in one patient, the paramedian diencephalic syndrome.

Epilepsia partialis continua was the chief initial complaint in a young diabetic who was found to have hyperosmolar non ketotic hyperglycaemia. Such a presentation in a juvenile diabetic is rare. Literature relevant to this interesting neurologic disturbance has been briefly reviewed.