tbuckley/cabot-search huggingface dataset:
Radionuclide cisternography in spontaneous intracranial hypotension with simultaneous leaks at the cervicothoracic and lumbar levels.
Authors: TAE JOO JEON, JONG DOO LEE, BYUNG IN LEE, DONG IK KIM, HYUNG SIK YOO
Journal: Clinical Nuclear Medicine (2001)

This case report clearly illustrates defined simultaneous cerebrospinal fluid leaks at the cervicothoracic and upper lumbar areas. A 53-year-old woman without a remarkable medical history was hospitalized for sudden onset of severe headache. The headache lasted more than 1 week and standing or sitting positions exaggerated the symptoms, although it was relieved when the patient was recumbent. Radionuclide cisternography was performed using 150 MBq (4 mCi) Tc-99m DTPA. It revealed two cerebrospinal fluid leaks from the cervicothoracic junction bilaterally and the left side of the upper lumbar area. Epidural blood patching was tried at the lumbar level (L1-L2) and showed only a transient effect. A second trial of this method at the level of C7-T1 performed 2 days later resulted in immediate improvement of the symptoms without recurrence. The simultaneous cerebrospinal fluid leaks were detected successfully with radionuclide cisternography using Tc-99m DTPA, which provided a useful guideline for treatment despite the limitations of delayed scanning.
Abstract 12053: Outcomes in Statin Intolerant Patients: The Cleveland Clinic Experience
Authors: Warner Mampuya, Leslie Cho, David Frid, Julie Huang, Michael Rocco, Danielle M Brennan, Stanley L Hazen
Journal: Circulation (2011)

Background: Intermittent statin dosing may provide beneficial lipoprotein changes and improve statin tolerance. Objective: To determine the tolerance and efficacy of intermittent low dose statins in patients previously intolerant to statin therapy. Methods: We performed a retrospective analysis of patients referred to the Cleveland Clinic Preventive Cardiology clinic for statin intolerance between January 1995 and March 2010. 1605 patients with at least 6 months follow-up were identified. Changes in lipid profile were analyzed. The number of patients achieving specified low-density lipoprotein cholesterol (LDL-C) goals, and tolerating different statin dosing regimens was assessed. Results: Seventy-three percent of patients with prior statin intolerance were able to tolerate a statin for the mean follow-up time of 49 months. Overall a median LDL-C reduction of 21% was achieved with 68% of patients reaching their ATP-III goals. Although patients on intermittent statin dosing (n=149) and those discontinued f...
Abstract 1889: Cardiac Resynchronization Therapy With Biventricular Pacing Improves Renal Function in Heart Failure Patients With Reduced Glomerular Filtration Rate
Authors: Guido Boerrigter, Lisa C Costello-Boerrigter, William T Abraham, Martin G St. John Sutton, Denise M Heublein, Kristin M Kruger, Michael R Hill, Peter A McCullough, John C Burnett
Journal: Circulation (2007)

Background: Renal dysfunction has emerged as an important independent prognostic factor in patients with heart failure (HF). Cardiac resynchronization therapy (CRT) improves functional status and left ventricular (LV) function in HF patients with ventricular dyssynchrony. We hypothesized that CRT would also improve glomerular filtration rate as estimated by the abbreviated MDRD equation (eGFR) in patients with reduced eGFR. Methods: This is a retrospective analysis of the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) study, which evaluated CRT in HF patients with NYHA class III–IV, ejection fraction ≤35%, QRS ≥130 ms, and stable medical regimen. Patients were evaluated before implantation and 6 months after randomization to control (CRT device OFF, n=225) or CRT (n=228). Patients were categorized according to their baseline eGFR: ≥90 (category A), 60≤eGFR&lt;90 (category B), and 30≤eGFR&lt;60 (category C) mL/min per 1.73m 2 . Changes in eGFR were also correlated with changes in other parameters in univariate analysis. Results: At baseline, reduced eGFR was associated with ischemic etiology, increased age, mitral regurgitation, and neurohumoral activation. CRT increased LV ejection fraction and decreased LV volumes and mitral regurgitation in all categories. Importantly, CRT improved eGFR (p=0.003) and reduced blood urea nitrogen (p=0.008) compared to control in category C, but not A (p=0.75/p=0.41) and B (p=0.43/p=0.89). In addition, only in category C did atrial natriuretic peptide decrease, suggesting reduced atrial distention and filling pressures with CRT in this group with impaired eGFR. In univariate analysis, changes in eGFR correlated weakly but significantly with changes in aldosterone (r=−0.22), plasma renin activity (r=−0.19, norepinephrine (r=−0.16), and mean blood pressure (r=+0.14), a pattern consistent with reduced neurohumoral activation due to increased systemic and renal perfusion pressure. Conclusions: CRT increased eGFR and reduced blood urea nitrogen in HF patients with reduced baseline eGFR. By improving cardiac function, CRT can indirectly improve renal function, underscoring the importance of cardiorenal interaction and providing another mechanism for the beneficial effects of CRT.
Use of quantum dots-based immunofluorescence nanotechnology for quantitative HER2 and ER detection in breast cancer tissue array to identify correlations in HER2-overexpressed and ER-positive breast cancer.
Authors: C. Chen, Y. Li, J. Peng, H. S. Xia, Y. P. Gong, D. W. Pang
Journal: Journal of Clinical Oncology (2010)

10624 Background: The correlations between HER2 and ER may help understand the endocrine therapy resistance in HER2 over-expressed and ER positive subtype breast cancer (BC). Quantum dots-based immunofluorescent nanotechnology (QDs-IHC) provides a promising alternative for quantitative and in situ detection of targets in molecular pathology.This study is to evaluate the quantitative correlations between HER2 and ER by QDs-IHC in HER2 over-expressed and ER positive BC. Methods: HER2 and ER of 240 BC tissue microarray specimens were detected by QDs-IHC and the signal information was acquired by CRi Nuance multispectral imaging system. The total and average fluorescence signals and positive distribution areas were calculated. The area of positive tumor cell of ER and HER2 were calculated based on the positive distribution of cytokeratin, which was used as internal control. HER2/cytokeratin ratio >30% was defined as HER2 positive BC. These patients were selected for HER2 and ER correction analysis. The associations of HER2 and ER and 5-year disease free survival (5-DFS) were also investigated. Results: Seventy six HER2 positive patients were selected, and their 5-DFS was 46.05% (35/76, media 46 months). The 5-DFS in the 25 ER negative patients (40%) was lower than that of 51 ER positive cases (49.02%), but without statistical significance (Log Rank test, P=0.336). However, the total signals, average signals and positive areas of HER2 were significantly higher in ER negative group than ER positive group (P<0.05). In ER positive group, there were an inverse correlation between HER2 and ER in terms total signals intensity (P=0.006, correlation coefficient: r = -0.381) and positive areas (P=0.019, r = -0.327). There were no significant differences in signal intensity and positive areas between relapse and non-relapse groups (P>0.05). There were no significant correlations between these values and time to disease relapse (P>0.05). Conclusions: The quantitative correlation between HER2 and ER is negative and not associated with 5-DFS in HER2 over-expressed and ER positive BC. No significant financial relationships to disclose.
Abstract 15722: Validity of HAS-BLED Score in Prediction of Major Bleeding Risk in Patients with Atrial Fibrillation Taking Warfarin and Dabigatran
Authors: Arismendy S Nunez, Wah Wah Htun, Kaushink Patel, John Kim, Omar Al-Awwad, George Fernaine
Journal: Circulation (2012)

Introduction Warfarin and dabigatran are used to prevent thromboembolism in patients with atrial fibrillation (AF). Although these medications can effectively prevent ischemic stroke, they are asso...
Abstract 577: Origin and Therapeutic Efficacy of Human Cardiac Progenitor Cells
Authors: Federico Mosna, Claudia Bearzi, Marcello Rota, Toru Hosoda, Jochen Tillmanns, Saori Yasuzawa-Amano, Irina Trofimova, Robert W Siggins, Nicole LeCapitaine, David A D’Alessandro, Elias Zias, Federico Quaini, Konrad Urbanek, Ornella Rimoldi, Robert E Michler, Roberto Bolli, Jan Kajstura, Annarosa Leri, William H Frishman, Piero Anversa
Journal: Circulation (2007)

To establish whether progenitor cells are present in the human heart (hCPCs) and have phenotypic properties distinct from human hematopoietic stem cells (hHSCs), samples of human myocardium were enzymatically dissociated and c-kit-positive-cells were sorted and plated immediately to obtain clones derived from single founder cells. By FACS analysis, freshly isolated hCPCs comprised 1.1±1.0% of the population and were negative for HSC markers, CD34 and CD133, and KDR. They were also negative for epitopes of monocytes, CD14 and CD16, mast cells, CD45, and lymphocytes, CD3 and CD20. The phenotype of hCPCs was completely different from that of human bone marrow cells which were positive for these surface antigens. Only small fractions of hCPCs expressed GATA4 and Nkx2.5. Of 1,530 seeded hCPCs, 11 clones were generated accounting for 0.7% cloning efficiency. Subsequently, these cells were injected in immunodeficient mice and rats at the time of coronary occlusion and 5 days after infarction. This was done to assess whether hCPCs differentiated into myocytes and coronary vessels immediately after ischemic injury and in the presence of a well-developed infarct. In both cases, hCPCs regenerated the infarcted myocardium. Connexin 43 and N-cadherin were detected between recipient rodent myocytes and newly formed human myocytes. The problem was then whether the structural integration of these two myocyte populations had a physiological counterpart. Studies were performed using an ex vivo preparation together with two-photon microscopy and laser line-scan imaging. EGFP-positive-hCPCs were injected in infarcted mice and the heart was studied 2-weeks later. The heart was perfused with an oxygenated Tyrode solution containing the calcium indicator Rhod-2 and stimulated at 1 Hz. Calcium transients was recorded in EGFP positive human myocytes and EGFP negative mouse myocytes. The synchronicity in calcium tracings between these two distinct cell pools was apparent, pointing to the functional integration of newly formed EGFP-positive human myocytes with the surrounding EGFP-negative mouse myocytes. Thus, the human heart contains hCPCs which are not of bone marrow origin and possess the ability to acquire the cardiomyocyte and coronary vascular cell lineages.
International Conference on Emerging Technologies in Gene/Drug Therapy and Molecular Biology
Authors: Kenneth Lundstrom
Journal: Molecular Therapy (2002)

Approximately 80 preclinical scientists and clinicians from Europe, North America, and Asia met at the beautiful island of Corfu for six days to discuss the latest developments in the field of molecular biology technologies related to gene therapy, application of gene delivery vectors in vivo in animal models, and clinical trials, mainly for cancer therapy. This was the fifth meeting organized by the International Society for Gene Therapy and Regulon Inc. in a relaxing atmosphere in the Greek archipelago.
Abstract 15117: S100A12 Protein is a Marker to Predict Cardiovascular Events in Patients with Chronic Coronary Artery Diseases
Authors: Toshinobu Saito, Yukihiro Hojo, Tomokazu Ikemoto, Takaaki Katsuki, Kazuyuki Shimada, Kazuomi Kario
Journal: Circulation (2011)

Purpose: S100A12, a calgranulin family protein released from activated macrophages, is involved in inflammatory cardiovascular diseases. S100A12 binds to receptor for advanced glycation-end product...
Current Concepts in Dermatology: II. The Skin and Systemic Disease
Authors: R JACKSON
Journal: JAMA (1963)

Many systemic diseases have cutaneous manifestations. In some diseases skin involvement is the predominant factor (Behçet's syndrome, urticaria pigmentosa, discoid lupus erythematosus and pseudoxanthoma elasticum); in others the skin manifestations, when present, are an important part of the condition (sarcoidosis, systemic lupus erythematosus, hypersensitivity angiitis, porphyria). This report includes descriptions of and comments on these cutaneous manifestations. Erythema nodosum and erythema multiforme are reaction patterns of the skin and mucous membrane which may have many causes. The relationship between discoid and systemic lupus erythematosus is discussed. There is little doubt that these are variations of the same basic disease process, even though the prognoses are very different.
Phase II study of gemcitabine and capecitabine in patients with metastatic breast cancer pretreated with anthracyclines and taxanes
Authors: J.-H. Ahn, S.-B. Kim, J.-S. Lee, Y.-K. Kang, W. K. Kim
Journal: Journal of Clinical Oncology (2005)

895 Background: The objective of this phase II study is to determine the efficacy and safety of the combination chemotherapy of gemcitabine and capecitabine, in patients with MBC previously treated with anthracycline- and taxane-containing regimens. Methods: Eligibility criteria included MBC with previous exposure to anthracycline and taxane; performance status (ECOG criteria) 0–2; age ≥ 20; adequate cardiac, pulmonary, hepatic, renal and bone marrow functions. Patients were given intravenous gemcitabine 1,000 mg/m2 (days 1 and day 8) and oral capecitabine 1,000 mg/m2 twice daily (days 1–14) every 3 weeks. According to Simon’s two stage phase II design, it was planned to enroll 48 patients hoping 40% response rate unless the study had to be terminated early due to poor response rate (≤3/13) at the first stage evaluation. Results: Between Mar. 2003 and Feb. 2004, a total of 14 patients received 73 cycles of treatment (median, 5 cycles/patient). Twelve patients received this regimen as a second-line treatment, and two as a third-line treatment for MBC. At the first stage evaluation, the response rate was 21.4% (95% CI, 0∼42.8%) in the intention-to-treat population (partial response 3, stable disease 5, progressive disease 5, not evaluated 1). The median response duration was 4.3 months (range, 2.1∼4.7+ months). Considering responders and patients with stable disease persisting more than 6 months, the clinical benefit rate was 42.9%. With a median follow-up of 10 months, median progression-free survival was 4.2 months (range, 1∼8.4+ months). Toxicities included grade III/IV neutropenia in 26% and 3%, and grade II/III hand-foot syndrome in 19% and 6% of cycles, respectively. Other non-hematologic toxicities were minimal and manageable. The median dose intensity of gemcitabine and capecitabine was 95.8% (range, 54∼100%), and 100% (range, 75∼100%), respectively. Conclusions: Although the combination of gemcitabine and capecitabine was well tolerated, its activity was less than expected in MBC patients previously treated with both anthracyclines and taxanes. Thus, this study had to be terminated early as planned. No significant financial relationships to disclose.
Abstract P313: Critical Cut-off Points of Serum Albumin Level that Indicate Abrupt Increase in Mortality Risk are Different Between Causes of Death Among Hemodialysis Patients
Authors: Takako Kidoguchi, Masaki Ohsawa, Kozo Tanno, Itai Kazuyoshi, Akira Okayama, Karen Kato, Yosuke Fujishima, Toshiyuki Onoda, Kiyomi Sakata, Kyoko Owada, Ritsuko Nekohira, Taeko Masuda, Tomoaki Fujioka
Journal: Circulation (2013)

Background: Hypoalbuminemia is a strong risk factor of all-cause death in dialysis patients. However, which cause of death is mainly attributed to hypoalbuminemia in dialysis patients and whether c...
Abstract 2893: Enhanced Myocardial Ischemic Tolerance in Hypercholesterolemic APOE Knockout Mice is Associated with Increased Expression of Caveolin 1 and Metallothionein
Authors: Lei Xi, Ali D Dursun, Yuan J Rao, Kathryn Loesser-Casey, Rakesh C Kukreja
Journal: Circulation (2008)

Hypercholesterolemia (HC) is an established risk factor for atherosclerosis and vascular endothelial dysfunction. Paradoxically, we and other investigators have found that animals with HCL are more resistant to myocardial ischemia-reperfusion (Isch-Rep) injury. However, the molecular mechanisms underlying this clinically relevant ischemia-resistant phenotype remain poorly understood. To this context, the present study was designed to identify novel molecular mediators for the HC-induced cardioprotection against Isch-Rep injury. Adult male C57BL/6J wild-type (C57BL-WT) mice and homozygous apolipoprotein E knockout (APOE-KO) mice were fed with regular rodent chow. The hearts were isolated and subjected to 20 min of zero-flow global Isch and 30 min of Rep in Langendorff mode. Infarct size and ventricular contractile function were assessed. Blood samples were collected from each mouse after the heart isolation procedure to measure serum total cholesterol (TCL). As summarized in Table 1 , the APOE-KO mice had developed HC, which was accompanied with significantly better post-Isch cardiac contractile function (DF and ±df/dt max ) and smaller infarct size as compared with C57BL-WT control mice. In a parallel series of experiments, heart tissues were collected from C57BL-WT and APOE-KO mice and total tissue lysates were prepared for Western blot analysis. We found significant enhancement in cardiac expression of caveolin 1 (Cav-1) and metallothionein (MT) in APOE-KO mice, whereas caveolin 3 (Cav-3) and T-complex protein 1beta (TCP-1beta) were significantly downregulated under HC. Electron microscopy revealed a selective increase in caveolae density on the endothelial cell membranes of APOE-KO mice. This study has provided the first evidence demonstrating that the remarkable ischemia-resistant phenotype of HC is associated with enhanced expression of two cytoprotective proteins - Cav-1 and MT in the heart. This research has received full or partial funding support from the American Heart Association, AHA National Center. Table 1
Abstract 14212: Association of CD34+ Circulating Progenitor Cells and C-Reactive Protein with Cardiovascular and All-cause Mortality in Hemodialysis Patients
Authors: Miho Tanaka, Hideki Ishii, Kazuhiro Kawashima, Yoshihiro Kawamura, Daisuke Kamoi, kyuichi Furuhashi, Yoshitaka Kumada, Toru Aoyama, Toyoaki Murohara
Journal: Circulation (2010)

Background:  Circulating endothelial progenitor cells (EPCs) are believed to be involved in maintenance of endothelial function, and are close proximity to CD34+ circulating progenitor cells (CPCs). C-reactive protein (CRP) also has been reported to reflect vascular wall inflammation and can predict future cardiovascular (CV) events. We investigated the association of CD34+ CPCs, CRP and their joint role in hemodialysis (HD) patients.   Methods:  The number of CD34+ CPCs was determined with the use of flow-cytometry in 216 HD patients. To avoid the influence of body fluid overload, the ratio of CD34+ CPCs to peripheral mononuclear cells (CD34+ / PMNCs) were calculated. The patients were divided into tertiles according to CD34+ / PMNCs levels; tertile 1 (T1):  0.023, and also to serum CRP levels; T1:  2.8mg/l, respectively. They were followed up for 5 years.   Results:  Serum CRP levels were 6.1±9.4mg/l, 3.1±4.1mg/l and 2.1±2.0mg/l in T1, T2 and T3 of CD34+ CPCs levels, respectively (p=0.0010), and were negatively correlated with CD34+ CPCs levels (r=0.31, p   Conclusions:  Reduced number of CD34+ CPCs and elevated CRP levels might be closely associated, and interactively increased mortality risk in HD patients.
Emergence and dissemination of the methicillin resistant Staphylococcus aureus USA300 clone in Denmark (2000-2005)
Authors: A R Larsen, M Stegger, R V Goering, M Sørum, R Skov
Journal: Eurosurveillance (2007)

The problem of methicillin resistant Staphylococcus aureus (MRSA) is increasing worldwide, and the spread of MRSA in the community challenges infection control since it is no longer restricted to hospital settings but involves private homes, places of work and kindergartens [1]. Furthermore, community acquired (CA)-MRSA may circumvent existing hospital infection control, since patients are rarely screened at admission. In the United States, the predominant CA-MRSA is defined by the Center for Disease Control (CDC) as the USA300 (ST8) clone. USA300 primarily causes skin and soft tissue infections (SSTI) in the community [2], but healthcare acquired infections with USA300 are rapidly emerging in the United States [3,4]. Comparison of the Danish collection of MRSA from 1997-2005 with the USA300 reference strain showed that USA300 has been introduced into Denmark on several occasions. Between 2000 and 2005, we identified 44 isolates which in addition to identical pulsed-field gel electrophoresis (PFGE) pattern shared other molecular characteristics with USA300: spa type t008 or closely related variants, Panton-Valentine leukocidin (PVL) positive and Staphylococcal Cassette Chromosome mec (SCCmec) type IVa. The isolates primarily caused SSTI, but cases of invasive infections were also encountered. The number of USA300 has increased several-folds in Denmark from 2003 to 2005 (2, 11 and 28 new cases, respectively) and with the experience from the US in mind, this is of great concern, especially as it is observed in a country with a long reputation for controlling MRSA.
Abstract 17054: N-Type Ca2+ Channel Blocker is Effective to Prevent Sudden Cardiac Death in Mice with Heart Failure
Authors: Yuko Yamada, Koichiro Kuwahara, Hideyuki Kinoshita, Yoshihiro Kuwabara, Yasuaki Nakagawa, Junko Shibata, Chinatsu Yamada, Takeya Minami, Shinji Yasuno, Satoshi Usami, Kazuyasu Nakao, Toshio Nishikimi, Kenji Ueshima, Yasuo Mori, Kazuwa Nakao
Journal: Circulation (2011)

Background - Increased sympathetic nerve activity is involved in the increased arrhythmogenicity seen in patients with chronic heart failure. N-type Ca 2+ channel (NCC) modulates sympathetic nerve activity by regulating calcium entry at sympathetic nerve terminal, which triggers the release of the neurotransmitter noradrenalin. The ability of NCC blockade to prevent lethal arrhythmias associated with heart failure has never been tested, however. Methods and Results - We compared effects of cilnidipine (Cil), dual N-and L-type Ca 2+ channel blocker, with those of nitrendipine (Nit), a selective L-type Ca 2+ channel blocker, in a cardiac-specific, dominant-negative form of neuron-restrictive silencer factor transgenic mice (dnNRSF-Tg), a mouse model of dilated cardiomyopathy leading to sudden arrhythmic death. Hemodynamic and echocardiographic analyses showed no significant difference among the control, Cil, and Nit groups. In contrast, Cil dramatically improved the survival rate (p&lt;0.001) and reduced ventricular arrhythmia (p&lt;0.05) among dnNRSF-Tg mice, compared with control vehicle or Nit. Cil improved the imbalance in autonomic nerve activity assessed by heart rate valiability, and also reduced the increased urinary excretion of noradrenalin seen in dnNRSF-Tg, whereas Nit did not. In addition to the pharmacological blockade, we also assessed the effect of genetic titration of NCC by crossing dnNRSF-Tg mice with the mice lacking CACNA1B encoding α1B subunit of NCC. In dnNRSF-Tg;CACNA1B +/- mice, survival rate was significantly improved compared with that in dnNRSF-Tg;CACNA1B +/+ mice (p=0.001). Conclusions - NCC blockade ameliorated disturbed autonomic nerve function and improved survival in a mouse model of dilated cardiomyopathy and sudden death. Our findings suggest NCC blockade is a potentially useful approach to preventing sudden cardiac death in patients with heart failure.