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941.
Ortiz PD Agarwal R Reddy R Lenge VV Civitello AB Flamm SD 《Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital》2006,33(3):386-388
Arrhythmogenic right ventricular dysplasia is a rare disorder that is familial in 30% to 50% of cases. It is characterized by structural and functional abnormalities of the right ventricle and a propensity for ventricular arrhythmias and sudden death. We report the case of a 59-year-old woman who had idiopathic, severe, right-sided heart failure and nonsustained ventricular tachycardia. She was diagnosed with arrhythmogenic right ventricular dysplasia by means of cardiac magnetic resonance imaging. We discuss the clinical features, diagnostic criteria, and role of cardiac magnetic resonance imaging in the diagnosis of arrhythmogenic right ventricular dysplasia. 相似文献
942.
BACKGROUND: Studies in several populations have indicated that genetic variation at the apolipoprotein E structural locus influences atherosclerosis leading to cardiovascular diseases. The possible role of apolipoprotein E polymorphism in the development of essential hypertension has not been sufficiently investigated. In this case-control study, we aimed to determine the significance of association between essential hypertension and apolipoprotein E genotypes. In addition, apolipoprotein E genotypes were correlated with serum lipid levels in order to understand the possible interaction between the specific genotype and the lipid profiles that can contribute to hypertension. METHODS AND RESULTS: The apolipoprotein E genotypes were assayed in 185 patients and 200 controls by polymerase chain reaction followed by enzymatic digestion with Hha I. Using logistic regression analysis, the multivariate-adjusted odds of hypertension were calculated. The incidence of epsilon4 allele was found to be significantly higher in patients (12.16%) than in controls (5.75%, chi2=10.87; p<0.05) and also in patients with positive family history (16.7%) as compared to negative family history (8.87%, chi2 = 8.45; p<0.1). Further, it was observed that carriers of epsilon4 allele have twice as much risk (p<0.05) for developing hypertension as compared to carriers of other alleles. Patients with epsilon4 allele had significantly higher levels of total cholesterol and low-density lipoprotein- cholesterol as compared to epsilon4 allele non-carriers (p<0.05). The adjusted odds ratios for epsilon4 and epsilon2 alleles versus epsilon3 allele were 2.2 (95% confidence interval 1.2 to 3.8, p<0.05) and 1.2 (95% CI, 0.75 to 1.77, p<0.514), respectively. CONCLUSIONS: Our study revealed a strong association of apolipoprotein E locus with hypertension and lipid profile. However, large population-based studies are needed to understand the exact role played by the locus in causing the condition. 相似文献
943.
Zumberg MS Reddy S Boyette RL Schwartz RJ Konrad TR Lottenberg R 《American journal of hematology》2005,79(2):107-113
Little is known about patterns of hydroxyurea (HU) use by community-based hematologist/oncologists (H/Os) for the treatment of sickle cell disease (SCD). Determination of these practice patterns pertaining to adult SCD patients was the focus of this study. A self-administered survey was mailed to H/Os in two southeastern states. Replies were received from 70% of eligible physicians. This study focuses on responses from 184 community H/Os and a comparison group of 30 university-based/affiliated H/Os providing ongoing care for at least 3 SCD patients/month. The majority of community H/O respondents saw less than 3 SCD patients/month. HU was prescribed by more than half (55%) of community H/Os in at least 10% of their patients. The most common reasons cited for prescribing HU include frequent painful crises (76%), chronic pain with frequent narcotic use (58%), and acute chest syndrome (43%). Although the majority of community H/Os care for few patients with SCD, the reported indications for HU were consistent with currently accepted recommendations. However, community H/Os reported acute chest syndrome, stroke, and pulmonary hypertension as indications for HU less often than the academic H/O group. Barriers to wider use of HU include physician concerns about carcinogenic potential, doubts about HU effectiveness, perceived patient apprehension about adverse effects, concern about lack of contraceptive use, and patient compliance. Further resources should focus on updating physicians on recently published material supporting the effectiveness of HU in symptomatic SCD as well as providing management guidelines to optimize the use of HU. 相似文献
944.
Cytoplasmic LEK1 is a regulator of microtubule function through its interaction with the LIS1 pathway 下载免费PDF全文
Soukoulis V Reddy S Pooley RD Feng Y Walsh CA Bader DM 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(24):8549-8554
LIS1 and nuclear distribution gene E (NudE) are partner proteins in a conserved pathway regulating the function of dynein and microtubules. Here, we present data that cytoplasmic LEK1 (cytLEK1), a large protein containing a spectrin repeat and multiple leucine zippers, is a component of this pathway through its direct interaction with NudE, as determined by a yeast two-hybrid screen. We identified the binding domains in each molecule, and coimmunoprecipitation and colocalization studies confirmed the specificity of the interaction between cytLEK1 and NudE. Confocal deconvolution analysis revealed that cytLEK1 exhibits colocalization with endogenous NudE and with the known NudE binding partners, LIS1 and dynein. By localizing the NudE-binding domain of cytLEK1 to a small domain within the molecule, we were able to disrupt cytLEK1 function by using a dominant negative approach in addition to LEK1 knockdown and, thus, examine the role of the cytLEK1-NudE interaction in cells. Consistent with a defect in the LIS1 pathway, disruption of cytLEK1 function resulted in alteration of microtubule organization and cellular shape. The microtubule network of cells became tightly focused around the nucleus and resulted in a rounded cell shape. Additionally, cells exhibited a severe inability to repolymerize their microtubule networks after nocodazole challenge. Taken together, our studies revealed that cytLEK1 is essential for cellular functions regulated by the LIS1 pathway. 相似文献
945.
Endoscopic ultrasound-guided trucut biopsy of the cyst wall for diagnosing cystic pancreatic tumors. 总被引:4,自引:0,他引:4
Michael J Levy Thomas C Smyrk Raghuram P Reddy Jonathan E Clain Gavin C Harewood Michael L Kendrick Randall K Pearson Bret T Petersen Elizabeth Rajan Mark D Topazian Kenneth K Wang Maurits J Wiersema Tony E Yusuf Suresh T Chari 《Clinical gastroenterology and hepatology》2005,3(10):974-979
BACKGROUND & AIMS: Nonoperative methods for diagnosis of pancreas cysts often lack sufficient accuracy. Accurate diagnosis is needed to determine prognosis and guide clinical management. The aim of this study was to determine whether the tissue obtained by endoscopic ultrasound-guided trucut biopsy (EUS TCB) is sufficient for histologic diagnosis of cystic pancreatic tumors (CPTs). METHODS: EUS TCB was performed in patients with a suspected CPT. A dedicated gastrointestinal pathologist reviewed the core biopsies. The final diagnosis was based on clinical, laboratory, imaging, and biopsy findings, and resected specimens when available. RESULTS: EUS TCB was performed in 10 patients with a suspected CPT. Final diagnoses included serous cystadenoma (SCA, n=5), islet cell tumor (n=2), mixed seromucinous lesion (n=1), polycystic disease of the pancreas (n=1), and pseudocyst (n=1). EUS TCB was nondiagnostic in 3 of 10 patients. Among the other 7 patients, TCB diagnosed 4 SCAs, obviating the need for planned surgery in 3 patients. In the fourth patient with an SCA, the TCB result ruled out metastatic disease from locally recurrent lung cancer, allowing a narrowed radiation field. EUS TCB confirmed the need for surgery in 2 patients with an islet cell tumor. In 1 patient, EUS TCB findings were "partially" diagnostic, leading to previously unplanned surgery. CONCLUSIONS: This report establishes the capability and safety of EUS TCB to collect sufficient tissue for diagnosing CPTs. The results might help guide clinical management. 相似文献
946.
Yang W Gauthier KM Reddy LM Sangras B Sharma KK Nithipatikom K Falck JR Campbell WB 《Hypertension》2005,45(4):681-686
5,6-epoxyeicosatrienoic acid (5,6-EET) is a cytochrome P450 epoxygenase metabolite of arachidonic acid that causes vasorelaxation. However, investigations of its role in biological systems have been limited by its chemical instability. We developed a stable agonist of 5,6-EET, 5-(pentadeca-3(Z),6(Z),9(Z)-trienyloxy)pentanoic acid (PTPA), in which the 5,6-epoxide was replaced with a 5-ether. PTPA obviates chemical and enzymatic hydrolysis. In bovine coronary artery rings precontracted with U46619, PTPA (1 nmol/L to 10 micromol/L) induced concentration-dependent relaxations, with maximal relaxation of 86+/-5% and EC50 of 1 micromol/L. The relaxations were inhibited by the cyclooxygenase inhibitor indomethacin (10 micromol/L; max relaxation 43+/-9%); the ATP-sensitive K+ channel inhibitor glybenclamide (10 micromol/L; max relaxation 49+/-6%); and the large conductance calcium-activated K+ channel inhibitor iberiotoxin (100 nmol/L; max relaxation 38+/-6%) and abolished by the combination of iberiotoxin with indomethacin or glybenclamide or increasing extracellular K+ to 20 mmol/L. Whole-cell outward K+ current was increased nearly 6-fold by PTPA (10 micromol/L), which was also blocked by iberiotoxin. Additionally, we synthesized 5-(pentadeca-6(Z),9(Z)-dienyloxy)pentanoic acid and 5-(pentadeca-3(Z),9(Z)-dienyloxy)pentanoic acid (PDPA), PTPA analogs that lack the 8,9 or 11,12 double bonds of arachidonic acid and therefore are not substrates for cyclooxygenase. The PDPAs caused concentration-dependent relaxations (max relaxations 46+/-13% and 52+/-7%, respectively; EC50 1micromol/L), which were not altered by glybenclamide but blocked by iberiotoxin. These studies suggested that PTPA induces relaxation through 2 mechanisms: (1) cyclooxygenase-dependent metabolism to 5-ether-containing prostaglandins that activate ATP-sensitive K+ channels and (2) activation of smooth muscle large conductance calcium-activated K+ channels. PDPAs only activate large conductance calcium-activated K+ channels. 相似文献
947.
OBJECTIVE: We recently demonstrated that patients with high levels of circulating dendritic cells (DC) and interleukin (IL)-12 are associated with reduced cancer relapse after hematopoietic stem cell transplantation. Identifying a growth factor that can promote these immune functions may have beneficial anti-tumor effects. We investigated the hypothesis that granulocyte-macrophage colony-stimulating factor (GM-CSF) induces IL-12 production and polarizes T lymphocytes toward a proinflammatory response. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMC), T lymphocytes, and antigen-presenting cells (APC) were cultured with GM-CSF and compared with no growth factors (control), G-CSF, or both GM-CSF and G-CSF. Cells were matured with either lipopolysaccharide or lectin (phytohemagglutinin). Type 1 and type 2 cytokines were measured by enzyme-linked immunosorbent assay. Induction of allogeneic T-lymphocyte proliferation induced by GM-CSF-stimulated APC was measured by mixed lymphocyte reaction. DC were measured by flow cytometry. RESULTS: Levels of type 1 (IL-12, interferon-gamma, tumor necrosis factor-alpha) cytokines increased while type 2 (IL-10 and IL-4) cytokines decreased after stimulation of PBMC, T lymphocytes, and APC with GM-CSF. APC treated with GM-CSF induced higher proliferation of allogeneic T cells. CD11c and CD123-positive DC proliferated after exposure to GM-CSF. Both subtypes of DC (DC1 and DC2) were increased by GM-CSF. CONCLUSIONS: GM-CSF induces production of type 1 proinflammatory cytokines by human PBMC, T lymphocytes, and APC. Type 2 cytokines are downregulated by GM-CSF and proliferation of allogeneic T cells is increased. These results demonstrate the potential for GM-CSF as a clinical agent for immune stimulation. 相似文献
948.
Ray IB Dukkipati S Houghtaling C McPherson CD Kastelein N Ruskin JN Reddy VY 《Journal of cardiovascular electrophysiology》2007,18(5):520-525
Objective: This study examined the feasibility of using a remote magnetic catheter navigation system (MNS) in concert with an EAM system to perform detailed left ventricular scar mapping and ablation in a porcine model of healed myocardial infarction.
Background : Substrate-based catheter ablation of ventricular tachycardia (VT) involves detailed electroanatomical mapping (EAM) of the ventricles. While a safe and effective procedure, VT ablation is nonetheless uncommonly performed, due in part to the technical challenges related to ventricular mapping.
Methods: Using a prototype EAM system (CARTO-RMT), seven chronically infarcted swine were mapped using either: (i) a standard manually manipulated catheter or (ii) a magnetic remotely manipulated (Niobe) catheter. A total of 191 ± 54 and 221 ± 64 points were acquired to map the chamber either manually or remotely, respectively.
Results: Procedure times were longer remotely (94 ± 22 vs. 59 ± 19 minute, P = 0.004; and 27 ± 8 vs. 18 ± 3 sec/point, P = 0.04), but this became less apparent with increased operator experience. However, the fluoroscopy time was significantly shorter with remote mapping (56 ± 56 vs. 244 ± 67 sec/map, P = 0.03). The calculated scar size was comparable between the two methods (16.3 ± 4.9 vs. 16.4 ± 4.8 cm2 , P = 0.37). Pathologic examination confirmed that the MNS was able to precisely deliver radiofrequency lesions to the scar borders. Using the MNS, the error to reach an evenly distributed set of endocardial targets was 6.6 ± 3.6 mm and 4.6 ± 2.0 mm, using transseptal and retrograde approaches, respectively.
Conclusions: Ventricular mapping using this remote navigation paradigm is technically possible and requires minimal fluoroscopy exposure, potentially facilitating ventricular substrate mapping and ablation. 相似文献
Background : Substrate-based catheter ablation of ventricular tachycardia (VT) involves detailed electroanatomical mapping (EAM) of the ventricles. While a safe and effective procedure, VT ablation is nonetheless uncommonly performed, due in part to the technical challenges related to ventricular mapping.
Methods: Using a prototype EAM system (CARTO-RMT), seven chronically infarcted swine were mapped using either: (i) a standard manually manipulated catheter or (ii) a magnetic remotely manipulated (Niobe) catheter. A total of 191 ± 54 and 221 ± 64 points were acquired to map the chamber either manually or remotely, respectively.
Results: Procedure times were longer remotely (94 ± 22 vs. 59 ± 19 minute, P = 0.004; and 27 ± 8 vs. 18 ± 3 sec/point, P = 0.04), but this became less apparent with increased operator experience. However, the fluoroscopy time was significantly shorter with remote mapping (56 ± 56 vs. 244 ± 67 sec/map, P = 0.03). The calculated scar size was comparable between the two methods (16.3 ± 4.9 vs. 16.4 ± 4.8 cm
Conclusions: Ventricular mapping using this remote navigation paradigm is technically possible and requires minimal fluoroscopy exposure, potentially facilitating ventricular substrate mapping and ablation. 相似文献
949.
Luis Fernando Calimano-Ramirez Taher Daoud Dheeraj Reddy Gopireddy Ajaykumar C Morani Rebecca Waters Kazim Gumus Albert Russell Klekers Priya R Bhosale Mayur K Virarkar 《World journal of gastroenterology : WJG》2022,28(40):5827-5844
Acinar cell carcinoma (ACC) is a rare pancreatic malignancy with distinctive clinical, molecular, and morphological features. The long-term survival of ACC patients is substantially superior to that of pancreatic adenocarcinoma patients. As there are no significant patient series about ACCs, our understanding of this illness is mainly based on case reports and limited patient series. Surgical resection is the treatment of choice for patients with the disease restricted to one organ; however, with recent breakthroughs in precision medicine, medicines targeting the one-of-a-kind molecular profile of ACC are on the horizon. There are no standard treatment protocols available for people in which a total surgical resection to cure the condition is not possible. As a result of shared genetic alterations, ACCs are chemosensitive to agents with activity against pancreatic adenocarcinomas and colorectal carcinomas. The role of neoadjuvant or adjuvant chemoradiotherapy has not been established. This article aims to do a comprehensive literature study and present the most recent information on acinar cell cancer. 相似文献
950.
BACKGROUND: The mechanisms leading to occlusion of plastic biliary stents (PBS) are not known. OBJECTIVE: To evaluate the impact of reducing duodenobiliary reflux on stent patency rate. DESIGN: A newly designed antireflux PBS (AR-PBS) was tested in vitro by using ox bile. A prospective randomized trial in human beings was conducted. SETTING: Tertiary medical center. PATIENTS: Patients with malignant bile-duct strictures were studied. INTERVENTIONS: A PBS or an AR-PBS stent was placed by using standard techniques, and the patients were followed at regular intervals. Patients presenting with stent occlusion underwent re-stent placement with either a PBS or a metal stent. MAIN OUTCOME MEASUREMENTS: In vitro: resistance to retrograde flow and comparison of the basal and peak antegrade flow pressures between the 2 stents. In vivo: stent patency rates, complications, and the efficacy of the stents in improving the liver test. RESULTS: The AR-PBS stent could withstand a retrograde pressure gradient of >320 mm Hg compared with <1 mm Hg for the PBS. Secondary to the siphon effect of the valve, the antegrade flow resistance offered by the AR-PBS was on the negative side for all flow rates compared with PBS (P < .001). The median patency of the AR-PBS in human studies was 145 days (range, 52-252 days) compared with 101 days (range, 41-210 days) for the PBS (P = .002). Both stents were equally effective in improving the liver test, and complication rates were similar in the 2 groups. LIMITATIONS: The occluded stents were not examined microscopically. CONCLUSIONS: The antireflux biliary stent remains patent for a longer time and hence duodenobiliary reflux may be contributing to stent occlusion. 相似文献