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991.
Ananth Viswanathan Claudio Spera Anmol Mullins David Covert Judit Banhazi Paul McDwyer Eibhlin Hudson Alberto Ferreira 《Advances in therapy》2017,34(7):1695-1706
Introduction
Few studies have examined outcomes and potential complications among glaucoma patients who are prescribed topical beta-blockers. This study examined resource usage (number of GP visits and hospitalizations) and diagnoses of respiratory or cardiovascular conditions among glaucoma patients prescribed beta-blockers compared to patients not prescribed beta-blockers.Methods
A retrospective cohort analysis was conducted using data from the UK Clinical Practice Research Datalink (CPRD) database over the period January 1, 2006 to March 31, 2014. Adult patients with at least one diagnosis of glaucoma were categorized into beta-blocker users and non-beta-blocker users. Beta-blocker users were further separated into patients that maintained beta-blocker therapy and patients that discontinued beta-blocker treatment in year 2 of the post-index period. The CPRD data was queried directly to obtain the number of GP visits, and hospitalizations were extracted by linking the CPRD and Hospital Episode Statistics (HES) patient-level data.Results
In the 12 months after being prescribed beta-blockers, patients that later discontinued beta-blocker treatment had a significantly higher average number of hospitalizations than patients that maintained beta-blocker therapy and the non-beta-blocker users (p < 0.05). In the year after beta-blocker initiation, there was a statistically significant within-group difference pre- and post-beta-blocker initiation for all groups, but the greatest number of GP visits occurred in the patients that subsequently discontinued beta-blocker treatment (mean 19.27). Patients that discontinued beta-blocker treatment were significantly more likely to have cardiovascular events than non-beta-blocker users in the post-index period (p < 0.05).Conclusion
This study suggests that the introduction of beta-blockers in a certain group of patients who later discontinue their use is associated with increased use of medical resources (higher number of GP visits and hospitalizations) in glaucoma patients in the UK, which may be indicative of a potential relationship between use of topical beta-blockers in glaucoma therapy and adverse outcomes.992.
Small vessel disease and cognitive impairment: The relevance of central network connections 下载免费PDF全文
Yael D. Reijmer Panagiotis Fotiadis Giovanni Piantoni Gregoire Boulouis Kathleen E. Kelly Mahmut E. Gurol Alexander Leemans Michael J. O'Sullivan Steven M. Greenberg Anand Viswanathan 《Human brain mapping》2016,37(7):2446-2454
Central brain network connections greatly contribute to overall network efficiency. Here we examined whether small vessel disease (SVD) related white matter alterations in central brain network connections have a greater impact on executive functioning than alterations in non‐central brain network connections. Brain networks were reconstructed from diffusion‐weighted MRI scans in 72 individuals (75 ± 8 years) with cognitive impairment and SVD on MRI. The centrality of white matter connections in the network was defined using graph theory. The association between the fractional anisotropy (FA) of central versus non‐central connections, executive functioning, and markers of SVD was evaluated with linear regression and mediation analysis. Lower FA in central network connections was more strongly associated with impairment in executive functioning than FA in non‐central network connections (r = 0.41 vs. r = 0.27; P < 0.05). Results were consistent across varying thresholds to define the central subnetwork (>50%–10% connections). Higher SVD burden was associated with lower FA in central as well as non‐central network connections. However, only central network FA mediated the relationship between white matter hyperintensity volume and executive functioning [change in regression coefficient after mediation (95% CI): ?0.15 (?0.35 to ?0.02)]. The mediation effect was not observed for FA alterations in non‐central network connections [?0.03 (?0.19 to 0.04)]. These findings suggest that the centrality of network connections, and thus their contribution to global network efficiency, appears to be relevant for understanding the relationship between SVD and cognitive impairment. Hum Brain Mapp 37:2446–2454, 2016. © 2016 Wiley Periodicals, Inc . 相似文献
993.
Paul Steinbok Chittur Viswanathan Gopalakrishnan Alexander R. Hengel Aleksander M. Vitali Ken Poskitt Cynthia Hawkins James Drake Maria Lamberti-Pasculli Olufemi Ajani Walter Hader Vivek Mehta P. Daniel McNeely Patrick J. McDonald Adrianna Ranger Michael Vassilyadi Jeff Atkinson Scott Ryall David D. Eisenstat Juliette Hukin 《Child's nervous system》2016,32(2):269-280
Background
Thalamic gliomas are rare. The natural history is unpredictable, and the optimal management of these tumors in children is poorly defined. The aim was to identify outcomes, prognostic factors, and response to various modalities of treatment in a relatively large population of pediatric thalamic tumors from many centers within a fairly homogeneous health care system.Methods
We performed a Canadian multicenter retrospective review of pediatric thalamic tumors presenting during the MRI era (1989–2012). Radiology and pathology were reviewed by central independent reviewers. Paraffin shavings for RNA extraction were taken and tested for fusion events involving KIAA1549:BRAF. Tumors were classified as unilateral or bithalamic based on their origin on imaging. Univariate and multivariate analyses on factors influencing survival were performed.Results
Seventy-two thalamic tumors were identified from 11 institutions. Females represented 53 % of the study population, and the mean age at presentation was 8.9 years. Sixty-two tumors were unilateral and 10 bithalamic. Unilateral tumors had a greater propensity to grow inferiorly towards the brainstem. These tumors were predominantly low grade in comparison to bithalamic tumors which were high-grade astrocytomas. The 5-year overall survival was 61?±?13 % for unithalamic tumors compared to 37?±?32 % for bithalamic tumors (p?=?0.097). Multivariate analysis indicated tumor grade as the only significant prognostic factor for unithalamic tumors. Six unilateral tumors, all low grade, were BRAF fusion positive.Conclusion
Unilateral and bilateral thalamic tumors behave differently. Surgical resection is an appropriate treatment option in unilateral tumors, most of which are low grade, but outcome is not related to extent of resection (EOR). Bilateral thalamic tumors have a poorer prognosis, but the occasional patient does remarkably well. The efficacy of chemotherapy and radiotherapy has not been clearly demonstrated. Novel therapeutic approaches are required to improve the prognosis for malignant unilateral thalamic tumors and bilateral thalamic tumors.994.
Lakshminarayanapuram G. Viswanathan Parthasarathy Satishchandra Bipin C. Bhimani Janardhan YC Reddy Batchu S. Rama Murthy Doddaballapura K. Subbakrishna Sanjib Sinha 《Annals of Indian Academy of Neurology》2016,19(3):339-343
Objective:This study aims to discuss the prevalence of polycystic ovary (PCO) and Polycystic ovary syndrome (PCOS) in women with epilepsy (WWE) on valproate (VPA), carbamazepine (CBZ), or phenobarbitone (PB), drug naive WWE and women with bipolar affective disorder (BPAD) on VPA.Results:Fifty-two women (52/190; 27.4%) had menstrual disturbances, in which oligomenorrhea was the most common (55.8%). There was a significant difference in the occurrence of PCOS in patients on VPA versus normal population (P = 0.05) and patients on other antiepileptic drugs (AEDs) (P = 0.02). There was, however, no significant difference in the occurrence of PCO between patients on VPA and the untreated epileptic women. VPA group (Epilepsy + BPAD) had a significantly higher occurrence of obesity than other treatment groups (P = 0.043, OR = 2.11).Conclusions:The study observed significantly higher occurrence of PCO in patients on VPA compared to other AEDs and the normal population. The importance of proper clinical evaluation before initiating VPA is highlighted. 相似文献
995.
Amal A. Aloud Veeramani Chinnadurai Mohammed A. Alsaif Khalid S. Al-Numair 《Pharmaceutical biology》2018,56(1):302-308
Context: Galangin, a natural flavonoid, is found in honey and Alpinia officinarum Hance (Zingiberaceae). Galangin has antiviral, antimicrobial, antidiabetic and anticancer properties, without side effects. The effects of galangin on hyperglycaemia and lipid abnormalities are not known.Objective: To elucidate the effectiveness of galangin on hyperglycaemia-associated complications and lipid changes in rats with streptozotocin (STZ)-induced hyperglycaemia.Materials and methods: Diabetes was induced in adult Wistar rats by administering 40?mg/kg of STZ. In our previous study, galangin had no toxicity at concentrations up to 320?mg/kg. Therefore three doses of galangin (4, 8 or 16?mg/kg BW) or glibenclamide (600 µg/kg BW) were administered daily to diabetic rats orally for 45 days.Results: Diabetic rats showed a significant (p?0.05) increased levels of plasma glucose (281.10?mg/dL) and decreased levels of insulin (6.01 μU/mL). Additionally, diabetic rats showed a significant (p?0.05) increased levels of plasma lipid profiles such as total cholesterol (149.05?mg/dL), triglycerides (143.28?mg/dL), free fatty acids (139.37?mg/dL), phospholipids (127.53?mg/dL), plasma low-density lipoprotein-cholesterol (98.72?mg/dL), plasma very low-density lipoprotein-cholesterol (28.65?mg/dL), and significant (p?0.05) decreased in plasma high-density lipoprotein-cholesterol (21.68?mg/dL). When galangin was administered to the hyperglycaemic rats, plasma glucose and insulin levels and lipid profiles reverted to levels similar to those in healthy control rats.Discussion and conclusions: Administration of galangin reduced hyperlipidaemia related to the risk of diabetic complications and could be beneficial for diabetic hyperlipidaemic patients. Further work detailing its mechanism-of-action for improving hyperglycaemic-associated lipid abnormalities is needed. 相似文献
996.
997.
High incidence of glucose intolerance in Asian-Indian subjects with acute coronary syndrome 总被引:4,自引:0,他引:4
Ramachandran A Chamukuttan S Immaneni S Shanmugam RM Vishnu N Viswanathan V Jaakko T 《Diabetes care》2005,28(10):2492-2496
OBJECTIVE: The risk of diabetes and coronary heart disease is high in Asian Indians. In this study, we aim to assess 1) the prevalence of hyperglycemia in incident acute coronary syndrome (ACS), 2) the effect of glycemia on the outcome, and 3) the association of plasma levels of insulin and proinsulin with ACS. RESEARCH DESIGN AND METHODS: A total of 146 nondiabetic subjects (121 men, 25 women) with ACS admitted to two hospitals in 1 year were enrolled. Random blood glucose at admission and a standard oral glucose tolerance test within 3 days were done. Glucose tolerance was categorized as normal glucose tolerance, impaired glucose tolerance (IGT) or impaired fasting glucose, and diabetes. Diabetes was arbitrarily classified further as undiagnosed (HbA1c [A1C] >6.0%) or possibly stress diabetes (A1C <6.0%). Subjects not on antidiabetic treatment were reassessed with a glucose tolerance test between 1 and 2 months. Fasting plasma specific insulin, proinsulin, their molar ratios, and insulin resistance (homeostasis model assessment) were estimated at baseline. RESULTS: Mean age of the cohort was 55 +/- 10.6 (SD) years. At baseline, 24 (16.4%) had normal glucose tolerance, 67 (45.9%) had IGT or impaired fasting glucose, and 55 (37%) had diabetes (35 [24%] were undiagnosed and 20 [13.7%] had stress diabetes). At follow-up, 53 of 92 responders (57.6%) continued to have IGT or diabetes. Mean baseline plasma insulin, proinsulin and its ratios, and insulin resistance were higher than normal in all subgroups. CONCLUSIONS: Nondiabetic Asian Indians showed a high prevalence of hyperglycemia following ACS. ACS was associated with insulin resistance and increased levels of specific insulin, proinsulin, and high proinsulin-to-insulin ratios. 相似文献
998.
Plasma adiponectin is an independent predictor of type 2 diabetes in Asian indians 总被引:16,自引:0,他引:16
Snehalatha C Mukesh B Simon M Viswanathan V Haffner SM Ramachandran A 《Diabetes care》2003,26(12):3226-3229
OBJECTIVE: Adiponectin, secreted by fat cells, has regulatory functions on energy metabolism. Its low levels are predictive of future development of diabetes. Because no studies on the regulatory role of adiponectin in glucose homeostasis in Asian Indians exist, this analysis was performed to determine the prospective association of adiponectin and diabetes in subjects with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: Baseline values of plasma adiponectin, results of anthropometry, fasting and 2-h plasma glucose levels, HbA(1c), results of lipid profile, and insulin resistance were analyzed in 91 subjects with IGT (53 men and 38 women) in a primary prevention study. Reassessment of glucose tolerance was performed during 1-year review. The predictive nature of adiponectin for development of diabetes was assessed using univariate and multiple logistic regression analyses. A control group comprising healthy, normoglycemic individuals was used for comparison. RESULTS: At follow-up, diabetes had developed in 25 of the 91 study subjects. The mean baseline adiponectin level was lower in the diabetic subjects than in the nondiabetic subjects (11.3 +/- 5.5 vs. 16.7 +/- 7.6 micro g/ml, P = 0.0017). Low adiponectin level was a strong predictor of future development of diabetes, and HbA(1c) also showed a positive predictive association. Women had higher adiponectin levels (16.4 +/- 6.1 micro g/ml) than men (13.9 +/- 7.6 micro g/ml) (P = 0.035). CONCLUSIONS: In Asian Indians, low plasma adiponectin level was predictive of future development of diabetes. 相似文献
999.
The diarrheagenic pathogen enteropathogenic Escherichia coli (EPEC) is responsible for significant infant mortality and morbidity, particularly in developing countries. EPEC pathogenesis relies on a type III secretion system-mediated transfer of virulence effectors into host cells. EPEC modulates host cell survival and inflammation, although the proximal signaling pathways have not been well defined. We therefore examined the effect of EPEC on the epidermal growth factor receptor (EGFR), a known upstream activator of both the prosurvival phosphoinositide 3-kinase/Akt and proinflammatory mitogen-activated protein (MAP) kinase pathways. EPEC induced the autophosphorylation of EGFR in intestinal epithelial cells within 15 min postinfection, with maximal phosphorylation being observed at 4 h. Filter-sterilized supernatants of EPEC cultures also stimulated EGFR phosphorylation, suggesting that a secreted component(s) contributes to this activity. EPEC-induced EGFR phosphorylation was blocked by the pharmacological inhibitor tyrphostin AG1478, as well as by EGFR-neutralizing antibodies. Inhibition of EGFR phosphorylation by AG1478 had no effect on bacterial adherence, actin recruitment to sites of attachment, or EPEC-induced epithelial barrier function alteration. EPEC-mediated Akt phosphorylation, however, was inhibited by both AG1478 and EGFR-neutralizing antibodies. Correspondingly, inhibition of EGFR activation increased the apoptosis/necrosis of infected epithelial cells. Inhibition of EGFR phosphorylation also curtailed EPEC-induced ERK1/2 (MAP kinase) phosphorylation and, correspondingly, the production of the proinflammatory cytokine interleukin-8 by infected epithelial cells. Our studies suggest that EGFR is a key proximal signaling molecule during EPEC pathogenesis. 相似文献
1000.
Neurometabolic coupling in cerebral cortex reflects synaptic more than spiking activity 总被引:2,自引:0,他引:2
In noninvasive neuroimaging, neural activity is inferred from local fluctuations in deoxyhemoglobin. A fundamental question of functional magnetic resonance imaging (fMRI) is whether the inferred neural activity is driven primarily by synaptic or spiking activity. The answer is critical for the interpretation of the blood oxygen level-dependent (BOLD) signal in fMRI. Here, we have used well-established visual-system circuitry to create a stimulus that elicits synaptic activity without associated spike discharge. In colocalized recordings of neural and metabolic activity in cat primary visual cortex, we observed strong coupling between local field potentials (LFPs) and changes in tissue oxygen concentration in the absence of spikes. These results imply that the BOLD signal is more closely coupled to synaptic activity. 相似文献