tbuckley/cabot-search huggingface dataset:
Abstract 3671: Dietary-induced Obesity in Mice results in Metabolic and Vascular Insulin-like Growth Factor 1 Resistance
Authors: Afroze Abbas, Helen Imrie, Hema Viswambharan, Adil Rajwani, Richard M Cubbon, Matthew B Kahn, Stephen B Wheatcroft, Mark T Kearney
Journal: Circulation (2008)

Endothelial cell dysfunction, characterised by a reduction in the bioavailability of nitric oxide (NO), plays an important role in the initiation of atherosclerosis. IGF-1 may be involved in the regulation of NO production via the Phosphoinositide 3-kinase (PI3-K)/Akt/eNOS pathway. In this study we have investigated whether dietary-induced obesity leads to disturbances of this pathway. C57/Blk6 mice fed a high fat diet for 20weeks (n=12) showed a significant increase in body weight and fat pad size when compared to chow fed controls (n=12). Blood pressure measurement showed an age-related increase in systolic blood pressure in high fat fed (19.2% from baseline) versus chow fed mice (7.6% from baseline). Blood glucose levels increased from 13.5 to 20mmol/l at 120mins in high fat fed mice, versus 5.7 to 7.3mmol/l in the chow fed group (p=0.009) by tolerance testing. In response to insulin, blood glucose fell by 72% in the chow fed group versus 48% in the high fat fed group (p= 0.0002). The high fat fed mice were less sensitive to IGF-1 stimulation than the chow fat mice by IGF-1 tolerance testing (p=0.046 at 30mins). The basal protein level of phosphorylated eNOS in the aortae of the high fat fed mice was 24.2% less than that of the chow fed mice. Upon IGF-1 stimulation levels of phosphorylated eNOS increased by 45.1% in the chow fed mice compared to a slight decrease of 5% in the high fat fed mice after normalisation to eNOS protein levels. eNOS activity in the aortae of chow fed mice, measured by an ex-vivo L-citrulline assay, showed an increase of 1.6-fold in response to IGF-1 (100 nM; 10 minutes) when compared to the high fat fed mice (n=5; p
Avoiding drug errors
Authors: D. S Nunn
Journal: BMJ (1995)

Avoiding drug errorsRead the label EDITOR,-The diversity of drug packaging that R E Ferner criticises has existed for many years.'What Ferner now identifies is a move towards standardisation through pharmaceutical manufacturers' adoption of the NHS ampoule labelling specification.The work leading to this has been described by Nunn.2The NHS specification seeks to establish a standard for labels, with the information presented in a consistent format and printed in the most legible way.The problem with diversity is that practitioners use features such as colour, shape, etc as a substitute for correct reading and inspection of the label.Use of such substitutes is both fallible and dangerous.The company whose products are illustrated in Femer's letter manufactures nearly 100 different ampoules.To differentiate between that number of products by use of colour, shape, etc is obviously impossible.Femer's hypothetical practitioner with modest presbyopia would obviously find it easier to read the labels illustrated than the text of the letter criticising the labels.The only way to be sure of the contents of an ampoule (or any other product) is to read the label.
Vitamin B12 deficiency
Authors: Ralph Green, Lindsay H. Allen, Anne-Lise Bjørke-Monsen, Alex Brito, Jean-Louis Guéant, Joshua W. Miller, Anne M. Molloy, Ebba Nexo, Sally Stabler, Ban-Hock Toh, Per Magne Ueland, Chittaranjan Yajnik
Journal: Nature Reviews Disease Primers (2017)
Characteristics of very poor outcome schizophrenia
Authors: Richard S. Keefe, Richard C. Mohs, Miklos F. Losonczy, Michael Davidson, Jeremy M. Silverman, Kenneth S. Kendler, Thomas B. Horvath, Rena Nora, Kenneth L. Davis
Journal: American Journal of Psychiatry (1987)

The authors compared 21 "Kraepelinian" schizophrenic patients who had been ill and dependent on others for the past 5 years with 76 chronic schizophrenic patients in remission or with exacerbations requiring hospitalization. The Kraepelinian patients met the criteria for schizophrenia by more diagnostic systems than the exacerbated patients, were less responsive to haloperidol, had more severe negative symptoms, and had similarly severe positive symptoms. They had cerebral ventricles that were more asymmetrical and a greater family history of schizophrenia spectrum disorders than the other chronic patients. These data suggest that patients with 5 years of illness and complete dependency on others may represent a subgroup of schizophrenia.
Abstract 9330: In-stent Restenotic Tissue with a Microchannel in Patients with Diabetes: Insights from Coronary Optical Coherence Tomography Image Analysis
Authors: Nobuaki Suzuki, Hiroyuki Kyono, Shuji Otsuki, Qiang Fu, Mutsuki Miyagawa, Naoyoshi Hosogoe, Tomohisa Saito, Shuichi Ishikawa, Akiyoshi Miyazawa, Hidenori Watanabe, Ken Kozuma, Takaaki Isshiki
Journal: Circulation (2011)

Introduction Coronary optical coherence tomography (OCT) allows the detection of subtle differences in patients with coronary artery disease. To date, OCT can virtually depict the various histological findings that occur at in-stent restenotic tissue. The present study investigated the clinical implications of microchannels located in in-stent restenotic sites. Methods We examined 48 consecutive in-stent restenotic (stenosis area, &gt;50%) coronary artery lesions from 44 patients who underwent coronary OCT. OCT images were obtained with a time-domain OCT imaging system. The images were acquired during automatic-pull back (1 mm/s; 20 frames/s). A microchannel was defined as the low signal cavity with a diameter of 50-150 µm (Figure; white arrows) and was evaluated by 2 independent analysts. A third analyst provided the final decision when there was a discrepancy between the first and second analysts. Diabetes was diagnosed in accordance with the guidelines of the Japanese Diabetes Society. Results In total, 16,008 frames were evaluated. Microchannels were detected in 464 (2.9%) frames from 24 (50%) lesions in 22 (50%) patients. The kappa statistic on the lesion level between the 2 analysts was 0.875. Diabetes was diagnosed in 23 (52.3%) patients, and 7 (15.9%) patients had insulin therapy. The incidence of microchannels was significantly more frequent in patients with diabetes (65.2% vs. 33.3%, p = 0.03). In contrast, none of the coronary risk factors (hypertension, dyslipidemia, smoking) other than diabetes showed a significant relationship with microchannel formation. Conclusion Microchannels were frequently observed at in-stent restenotic tissue sites in patients with diabetes. The results indicated that microvessel formation, which is a common diabetic complication, is a unique pathophysiological factor of in-stent restenosis in patients with diabetes. Neovascular formation may be targeted to prevent in-stent restenosis in patients with diabetes.
Cerebrospinal fluid monoamine metabolites in childhood-onset schizophrenia
Authors: L K Jacobsen, J A Frazier, A K Malhotra, F Karoum, K McKenna, C T Gordon, S D Hamburger, M C Lenane, D Pickar, W Z Potter, J L Rapoport
Journal: American Journal of Psychiatry (1997)

Pediatric studies of cerebrospinal fluid (CSF) monoamine metabolites in childhood-onset schizophrenia may help to elucidate both pathophysiology and treatment response in early-onset psychosis.CSF homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) and serum prolactin were measured during drug-free and antipsychotic medication conditions in 18 patients (mean age = 14.2 years, SD = 1.7) who had onset of schizophrenia by age 12 (mean age at onset = 9.9 years, SD = 1.8). Relationships between changes in CSF monoamines and serum prolactin and clinical outcome were examined, and the degree of change in CSF monoamines in response to clozapine treatment was compared with that for 16 patients with later-onset schizophrenia.Despite patients' significant clinical improvement with treatment, CSF monoamine concentrations and ratios of HVA/5-HIAA and HVA/MHPG did not significantly change with 6 weeks of either haloperidol or clozapine treatment. Serum prolactin levels increased during haloperidol treatment. Clozapine had similar effects on CSF monoamines in patients with childhood- and later-onset schizophrenia.While these data are compatible with continuity between childhood- and later-onset schizophrenia, they also highlight the complexity of the biochemical events mediating clinical changes in schizophrenia.
Abstract 4710: Diagnostic Accuracy of Myocardial Perfusion on Myocardial Contrast Echocardiography in Patients with Acute Coronary Syndrome: Results from the Assessment of Coronary Heart Disease with Myocardial Contrast Echocardiography 2 (ACTMCE2) Multicenter Trial
Authors: Konomi Sakata, Hiroshi Ito, Hiroshi Wada, Hiroyuki Watanabe, Tadamichi Sakuma, Satoshi Yamada, Kaoru Doi, Tomoyuki Watanabe, Hideaki Yoshino, Katsuomi Iwakura, Young-jae Lin, Takahiro Ota, Junichi Yoshikawa
Journal: Circulation (2008)

Background: Intravenous myocardial contrast echocardiography (MCE) at rest and during vasodilator stress is a reliable bedside technique for assessment of myocardial perfusion in patients with coronary artery disease. The aim of this study is to evaluate diagnostic accuracy of myocardial perfusion abnormalities using MCE at rest in patients with acute coronary syndrome (ACS). This study is the first MCE multicenter trial for the evaluation of ACS in Japan. Methods: We performed triggered MCE at rest in 102 patients (mean age: 65 ± 11 years) with suspected ACS. We obtained 1:1 and 1:6 end-systolic triggered MCE images at four- and two-chamber views. We detected myocardial ischemia by the appearance of myocardial perfusion abnormalities (defect or reduction) in 1:1 end-systolic triggered MCE image. We assessed the appearance of regional wall motion abnormality (RWMA) at the same time. Quantitative coronary angiography was performed in all patients within 1 week (2.6 ± 2.2 days) after MCE. Results: Eighty-four of 102 (82%) patients were diagnosed ACS (unstable angina: 70 patients; non-ST-segment elevation myocardial infarction: 11 patients; ST-segment elevation myocardial infarction: 3 patients) and demonstrated significant coronary artery stenosis (stenosis = or &gt;75%) that required coronary revascularization therapy. The sensitivity, specificity, and accuracy of myocardial perfusion abnormality by MCE at rest for diagnosing ACS were 79%, 86%, and 83%, respectively. On each coronary artery, the sensitivity, specificity, and accuracy of MCE for diagnosing ACS were 85%, 71%, and 79% in the left anterior descending artery; 70%, 92%, and 84% in the left circumflex artery; 77%, 89%, and 84% in the right coronary artery, respectively. The sensitivity, specificity, and accuracy of RWMA for diagnosing ACS were 49%, 90%, and 71%, respectively, and the sensitivity of MCE for diagnosing ACS was significantly higher than that of RWMA. Conclusion: Intravenous myocardial contrast echocardiography at rest without stress examination is a feasible noninvasive method for accurate diagnosis of ACS. In this multicenter study, MCE at rest improved the diagnostic accuracy of echocardiography for diagnosing ACS.
Abstract 940: C-kit Positive Cardiac Progenitor Cells Contribute to the Embryonic Development of the Heart
Authors: Grazia Iaffaldano, Yu Misao, Nicole LeCapitaine, Claudia Bearzi, Arantxa Gonzalez, Toru Hosoda, Konrad Urbanek, Marcello Rota, Edmund H Sonnenblick, Sergio Ottolenghi, Leonard G Meggs, Annarosa Leri, Piero Anversa, Jan Kajstura
Journal: Circulation (2007)

Recently, a compartment of c-kit positive cardiac progenitor cells (CPCs) has been identified in the adult mouse heart. Whether CPCs are restricted to the adult myocardium or are present throughout ontogenesis and contribute to heart development is unknown. For this purpose, a transgenic mouse in which EGFP was driven by the c-kit promoter was employed. C-kit-EGFP positive cells were present in the heart at all stages of embryonic and fetal development, and their number increased with time reaching 400 cells at E17. Symmetric and asymmetric division of c-kit-positive cells was identified respectively by the uniform and non-uniform localization of the endocytic proteins, Numb and α-adaptin. The presence of symmetric and asymmetric division was consistent with the rapid expansion of the pool of c-kit positive cells and the simultaneous generation of a committed progeny. A fraction of c-kit-EGFP positive cells expressed the myocyte transcription factors Nkx2.5 and MEF2C or specific sarcomeric proteins, α-sarcomeric actin, β-cardiac actinin, β-myosin heavy chain and troponin T. These findings demonstrated a linear relationship between CPCs and myocyte formation. Importantly, observations by two-photon microscopy showed that c-kit-EGFP positive cells in the forming heart exhibited morphogenic movements. Conversely, c-kit-EGFP positive cells from extracardiac regions or from the yolk sac did not translocate to the developing heart. Importantly, cardiac c-kit positive cells were negative for markers of hematopoietic stem cells CD34 and CD45. When c-kit-EGFP-positive cells were isolated from the embryonic heart and plated in vitro at limiting dilution, they formed single-cell derived clones. Almost all cells in the clones continued to express c-kit and EGFP. However, few cells located at the periphery of the clones were no longer positive for c-kit and EGFP and began to express sarcoplasmic proteins. In conclusion, c-kit positive cells in the developing myocardium exhibit the properties of stem cells; they are clonogenic and self-renewing and participate in the growth of the embryonic and fetal heart.
Abstract 12671: Distinct Metabolic Flow Enables Large-Scale Purification of Pluripotent Stem Cell-Derived Cardiomyocytes
Authors: Shugo Tohyama, Fumiyuki Hattori, Motoaki Sano, Takako Hishiki, Yoshiko Nagahata, Tomofumi Tanaka, Shinsuke Yuasa, Makoto Suematsu, Keiichi Fukuda
Journal: Circulation (2011)

Background Mass production of highly purified cardiomyocytes is a critical bottleneck in realizing heart regenerative therapy. Our recently established non-genetic purification method of cardiomyoc...
Abstract 1274: Syndecan-4 Pathway Interception Reduces Infarct Size After Myocardial Ischemia And Impacts On Remodelling
Authors: Frank Echtermeyer, Svenja Hubrich, Christine Herzog, Anke Hahnenkamp, JÃ¶rg M Stypmann, Gregor Theilmeier
Journal: Circulation (2007)

Objectives: Reperfusion injury after myocardial ischemia is governed by leukocyte recruitment. Syndecan-4 (SDC4) has been shown to be a major regulator of cell-cell and cell-matrix interactions. We tested if the SDC4-pathway impacts on myocardial necrosis, tissue loss and remodeling in mouse models of myocardial ischemia/infarction. In addition we analyzed the role of SDC4 in leukocyte recruitment in vitro and in mouse peritonitis. Methods: Syndecan4-deficient (SDC4 −/− ) or wildtype (WT) mice were subjected to transient (30 min; MI/R) or permanent (MI) LAD-ligation. In MI/R, after reperfusion for 24h, infarct size was measured by lack of TTC-staining. The extracellular SDC4-domain (ED-SDC4) was systemically overexpressed by hydrodynamic transfection (HDTF). Echocardiography revealed LV-function 4 days after MI(/R). Neutrophil extravasation was tested by lavaging mice 4h after IP-injection of thioglycollate. Adhesion of SDC4 −/− - or WT-PMN to resting or TNFα-activated, SDC4-siRNA-treated mouse endothelioma cells (EC) was tested in an adhesion assay. Results: Infarctions after MI/R were 43±7% larger in SDC4 −/− compared to WT (p&lt;0.01, n=8). ED-SDC4-HDTF reduced infarct size by 27±4% (p&lt;0.05, n=6). LV-function after MI was significantly worse in WT than SDC-4-KO (EF pre-post : −45±7% and −55±8%; p&lt;0.05). In SDC4 −/− LV-dilation after MI was significantly ameliorated (EDV post-pre : 28±7μl vs. 39±8μl, SDC4 −/− vs WT, p&lt;0.05). Emigration of GR-1 + -PMN of SDC4 −/− was increased by 2±0.5-fold in peritoneal lavages (n=6, p&lt;0.05). SDC4 knock down (−80% in RT-PCR) in EC augmented adhesion of PMNs to resting EC by 41±8% and TNFα-activated EC by 20±5%. Adhesion of SDC-4-KO-PMN to resting and TNFα-activated EC was increased by 22±5% and 16±5%. SDC-4-KO-PMN adhesion to activated SDC4 knock down-EC was increased by 40±5% (p&lt;0.05, n=3). Conclusion: SDC-4 is a powerful regulator of leukocyte-endothelial interactions and directly links molecular events driving myocardial necrosis and dilatative remodelling. Lack of SDC-4 increases, soluble SDC4 decreases infarct size. SDC4-deficiency reduces dilatative remodelling after MI. Therefore SDC4 beneficially influences early tissue necrosis after ischemia but adversely influences cardiac remodelling.
Abstract 3559: Insulin Receptor Substrates (IRS) Signaling are Essential Regulators of Mitochondrial Function and Cardiomyocyte Survival
Authors: Christian Riehle, Benjamin Wayment, Karla M Pires, Annie B Moreira, Heather Theobald, Xiaocheng Dong, Morris F White, Sheldon E Litwin, E. Dale Abel
Journal: Circulation (2008)

It has recently been reported that impaired PI3K signaling leads to cardiac mitochondrial dysfunction and that cardiac insulin receptor deficiency impairs cardiac growth. Signaling from insulin and insulin-like growth factor 1 receptors to PI3K is mediated by insulin receptor substrates (IRS) 1 and 2. Our objective was to determine the contribution of IRS isoforms on cardiac structure, mitochondrial and contractile function. For this purpose we generated mice with cardiomyocyte-specific deletion of IRS1 (CIRS1KO) or IRS2 (CIRS2KO) or IRS1 + IRS2 (CIRS12KO). While the single KOs had normal survival, CIRS12KO mice died from heart failure within the first eleven weeks of life. At the age of 8 weeks, heart weight-to-tibia length ratios, HW/TL were reduced by 11% (p&lt;0.05) in CIRS1KO versus WT. ADP-stimulated mitochondrial oxygen consumption (V-ADP) was decreased by 22% (p&lt;0.05) and ATP synthesis by 16% (p&lt;0.05) in saponin-permeabilized cardiac fibers using pyruvate as substrate but not with palmitoyl carnitine (PC) or glutamate. In contrast, HW/TL was unchanged in CIRS2KO at the age of 8 weeks and was increased at the age of 14 weeks (+7%, p&lt;0.05). Similarly, ADP-stimulated respirations were reduced in CIRS2KO at both ages by −21% and −16% respectively, (p &lt; 0.05) only with pyruvate as substrate. In contrast, CIRS12KO developed dilated cardiomyopathy at the age of 4 weeks (LVDs + 18.9%, LVPWd −12.7%, LVPWs −21.4%, FS −36.7%, EF −26.3%, p&lt;0.05). Histology revealed myofibrillar loss and disarray and increased fibrosis. Using stereology, cardiomyocyte nuclei per area was reduced by 27% and cardiomyocyte cross-sectional area was increased by 33% (both, p&lt;0.05). Using pyruvate, PC or glutamate as substrates, V-ADP and ATP-synthesis rates were reduced by 33– 41%. Transcriptional analysis revealed a coordinate downregulation (by 40 – 60%) of PDK4 and PDH subunits, FAO and OXPHOS genes that were associated with a 35% reduction in expression of PGC-1β. At the protein level, expression of the complex II subunit, succinate-ubiquinol oxidoreductase was reduced by −51% (p&lt;0.01). These data identify a critical role for IRS-mediated signaling in the regulation mitochondrial gene and protein expression, mitochondrial function and cardiomyocyte survival.
Simple PCR detection of haptoglobin gene deletion in anhaptoglobinemic patients with antihaptoglobin antibody that causes anaphylactic transfusion reactions
Authors: Yoshiro Koda, Yoshihisa Watanabe, Mikiko Soejima, Eiko Shimada, Motoko Nishimura, Kaichiro Morishita, Susumu Moriya, Shigeki Mitsunaga, Kenji Tadokoro, Hiroshi Kimura
Journal: Blood (2000)
Analysis of 96 abnormal brain scans using technetium 99m (pertechnetate form)
Authors: J. L. Quinn
Journal: JAMA (1965)

Technetium 99m, in the pertechnetate form, was evaluated as an agent for brain scanning.<sup>99m</sup>Tc has a physical half-life of six hours and no particulate radiation emission; large doses (10 to 15 mc) were administered without excessive patient irradiation. The scanning speed was increased and a single view of the brain recorded in five minutes. Because pertechnetate is cleared slowly from the blood, the normal intracranial vascular structures, not seen with chlormerodrin Hg 197 and chlormerodrin Hg 203, are depicted on the scan. In our study of 625 patients, 54 of 65 patients with proved intracranial neoplasia had positive results from brain scans. Forty-one patients with a variety of nonneoplastic intracranial diseases had positive scans.<sup>99m</sup>Tc, in the pertechnetate form, was found to be as nonspecific as chlormerodrin Hg 197 and chlormerodrin Hg 203 in outlining intracranial disease.
One and two view mammography in breast cancer
Authors: A H S Lee, L G Bobrow, R R Millis
Journal: BMJ (1996)

children becomes concentrated in large, tertiary paediatric intensive care units.1 Training junior doctors in more than just the basic sldlls of resuscitation will be easier in centres with a high throughput of patients, and ultimately this will enable a higher standard of care to be delivered in local hospitals, where most of these doctors will eventually work.T SAJJANHAR Feliow in paediatric intensive care MJMARSH Consultant in psediatric intensive care I A MURDOCH Consultant in paediatric intensive care Guy's Hospital, London SE1 9RT
Abstract 11852: Co-administration of Aleglitazar and Ibuprofen has no Additional Effect on Renal Function Compared to Ibuprofen Alone
Authors: Agnes Portron, Carolina Pellanda, Alan Marion, Ruth Penn, Zainab Ansari, Annette Sauter, Thorsten Ruf
Journal: Circulation (2012)

Introduction: Aleglitazar is a balanced activator of peroxisome proliferator-activated receptor (PPAR)-α and γ, in Phase III development for reduction of cardiovascular mortality and morbidity foll...
The Effect of Donor Age on Corneal Transplantation Outcome
Authors: gal Rl, Dontchev M, Beck Rw, Mannis Mj, Holland Ej, Kollman C, Dunn Sp, Heck El, Lass Jh, Montoya Mm, Schultze Rl, Stulting Rd, Sugar A, Sugar J, Tennant B, Verdier Dd
Journal: Ophthalmology (2008)