tbuckley/cabot-search huggingface dataset:
STIM1: a new therapeutic target in occlusive vascular disease?
Authors: A. Agrotis, C. Koulis
Journal: Cardiovascular Research (2008)

Improvements in interventional cardiology arising from stent development have significantly increased the efficacy of angioplasty as a primary treatment for atherosclerotic artery disease. Nevertheless, this procedure is still prone to failure in some patients due to the occurrence of neointimal hyperplasia that contributes to restenosis, lumen loss, and reduction in blood flow. In addition, late-stent thrombotic complications may also arise in some instances in which anti-proliferative drug-eluting stents are used, due to compromised reendothelialization subsequent to the angioplasty procedure. The development of neointimal hyperplasia is a complex phenomenon, with multiple mechanisms and molecules being involved. Angioplastic denudation of the endothelial barrier overlying the smooth muscle cell (SMC) layers in the intima and media provides a surface which is now more prone to the increased accumulation of circulating cells such as leucocytes and platelets. Subsequently, a number of cytokines and chemokines interact to lead to an inflammatory response, which is associated with a phenotypic modulation of the resident SMCs from a normally ‘contractile’ phenotype to a ‘synthetic’ phenotype. In this synthetic phenotype, the SMCs are more sensitive to migratory and proliferative stimuli and have an increased propensity for extracellular matrix production,1 critical processes involved in the development of neointimal hyperplasia subsequent to angioplasty. Among the key underlying mechanisms that facilitate the increased SMC migratory/proliferative capacity are those … 

*Corresponding author. Tel: +61 3 8532 1189; fax: +61 3 8532 1100. E-mail address: alex.agrotis{at}bakeridi.edu.au
Defective release of C5a related chemo-attractant activity from complement in Crohn's disease.
Authors: J Elmgreen, A Berkowicz, H Sorensen
Journal: Gut (1983)

Complement was studied in 20 untreated cases of Crohn9s disease and in 20 healthy volunteers by an in vitro activation of the cascade reaction. Total haemolytic complement was normal in all patients. In contrast, activation of the alternative pathway lead to a decreased release of C5a related chemo-attractant activity together with a subnormal utilisation of the main complement component C3. This abnormality of complement function was not related to the activity of the disease, site of involvement or to disease duration. The results suggest that an inadequate stimulation of important neutrophil functions may result when bacterial lipopolysaccharides and other macromolecules activating the alternative pathway penetrate the gut mucosa. A delayed clearance from the tissue of such foreign material could be a further pathogenic factor in Crohn9s disease leading to granulomatous inflammation by a foreign body reaction.
Childhood arterial ischaemic stroke incidence, presenting features, and risk factors: a prospective population-based study
Authors: Andrew A Mallick, Vijeya Ganesan, Fenella J Kirkham, Penny Fallon, Tammy Hedderly, Tony McShane, Alasdair P Parker, Evangeline Wassmer, Elizabeth Wraige, Samir Amin, Hannah B Edwards, Kate Tilling, Finbar J O'Callaghan
Journal: The Lancet Neurology (2013)
New Tumor-Node-Metastasis Staging Strategy for Node-Positive (stage III) Rectal Cancer: An Analysis
Authors: Frederick L. Greene, Andrew K. Stewart, H. James Norton
Journal: Journal of Clinical Oncology (2004)

The tumor-node-metastasis system for staging rectal cancer is based on invasion, number of involved nodes, and metastasis. Nodes are classified as N1 or N2 according to the number involved with metastases. Nodal positivity defines stage III regardless of depth of invasion or number of positive nodes. Our purpose was to analyze overall survival when node-positive patients were stratified into three new subsets.We analyzed data entered into the National Cancer Data Base for 5,987 stage III patients with rectal cancer between 1991 and 1993. Survival was calculated using three new subgroups (IIIA: T1/2, N1; IIIB: T3/4, N1; IIIC: any T, N2). Survival following surgery and adjuvant therapy was assessed. The observed survival rates were calculated and compared using the log-rank method. The Cox regression model assessed subgroup differences.Five-year observed survival rates for stage III subcategories were 55.1% in IIIA; 35.3% in IIIB; and 24.5% in IIIC. Stratifying for treatment outcome, stage IIIA patients having surgery alone (n = 278) had poorer observed 5-year survival (39%) than patients treated with surgery and adjuvant chemotherapy or radiation therapy (chemo/XRT; n = 765; 60%). Similar outcomes occurred in IIIB (surgery-alone [n = 726; 21.7%] and chemo/XRT [n = 2,130; 40.9%] groups) and in IIIC (surgery-alone [n = 467; 12.2%] and chemo/XRT [n = 1,621; 28.9%] groups). Differences were significant (P <.0001) in all stages.The traditional stage III designation of rectal cancer fails to account for invasion (T1-4) and number of involved nodes (N1, N2). The stratification of stage III patients into three subsets should be used in future analyses of rectal cancer. The effect of postoperative adjuvant therapy was beneficial in all subsets.
Long-term carcinogenicity study in Syrian golden hamster of particulate emissions from coal- and oil-fired power plants.
Authors: S A Persson, M Ahlberg, L Berghem, E Könberg, G F Nordberg, F Bergman
Journal: Environmental Health Perspectives (1988)

Male Syrian golden hamsters were given 15 weekly intratracheal instillations with suspensions of coal fly ash or oil fly ash. Controls were instilled with saline containing gelatine (0.5 g/100 mL) or to check particle effects with suspensions of hematite (Fe2O3). The common weekly dose was 4.5 mg/hamster. In addition, one subgroup of hamsters was treated with oil fly ash at a weekly dose of 3.0 mg/hamster and another with coal fly ash at a weekly dose of 6.0 mg/hamster. Other groups of hamsters were treated with suspensions of benzo[a]pyrene (BaP) or with suspensions on coal fly ash, oil fly ash, or Fe2O3 coated with BaP. The mass median aerodynamic diameters of the coal and oil fly ashes were 4.4 microns and 28 microns, respectively. Hamsters treated with oil fly ash showed a higher frequency of bronchiolar-alveolar hyperplasia than hamsters in the other treatment groups. Squamous dysplasia and squamous metaplasia were most frequent in animals treated with suspensions of BaP or BaP-coated particles. The earliest appearance of a tumor, the highest incidence of tumors, and the highest incidence of malignant tumors were observed in hamsters treated with oil fly ash coated with BaP. Squamous cell carcinoma and adenosquamous carcinoma were the most frequent malignant tumors. No malignant tumors and only few benign tumors were observed in hamsters instilled with suspensions of fly ash not coated with BaP. The present study gives no indication that coal fly ash could create more serious health problems than oil fly ash.
Protein Tyrosine Kinase Is Not Involved in the Infarct Size–Limiting Effect of Ischemic Preconditioning in Canine Hearts
Authors: Masafumi Kitakaze, Koichi Node, Hiroshi Asanuma, Seiji Takashima, Yasuhiko Sakata, Masanori Asakura, Shoji Sanada, Yoshiro Shinozaki, Hidezo Mori, Tsunehiko Kuzuya, Masatsugu Hori
Journal: Circulation Research (2000)

Abstract —Protein kinase C (PKC) plays an important role in ischemic preconditioning (IP). Because (1) tyrosine kinase is located at the downstream of PKC for IP in the rabbit hearts and (2) we have reported that ecto–5′-nucleotidase is the substrate for PKC and plays a crucial role for the infarct size–limiting effect, we tested whether tyrosine kinase activation contributes to either activation of ecto–5′-nucleotidase or the infarct size–limiting effect of the early phase of IP in the canine heart. In dogs, the IP procedure (4 cycles of 5-minute occlusion of coronary artery) and exposure to 12,13-phorbol myristate acetate (PMA) each activated myocardial ecto–5′-nucleotidase and Lck tyrosine kinase. Genistein (10, 30, and 100 μg · kg − 1 · min − 1 IC), an inhibitor of tyrosine kinase, attenuated the activation of Lck tyrosine kinase but did not attenuate the activation of ecto–5′-nucleotidase due to either IP or PMA. In the other canine hearts, IP attenuated infarct size (49±5 versus 11±3 or 16±3%, P &lt;0.01) due to 90 minutes of coronary occlusion followed by 6 hours of reperfusion, which was not blunted by 3 or 2 (30 and 100 μg · kg − 1 · min − 1 ) doses of genistein (infarct sizes, 15±4, 13±4, and 13±3%, respectively, and 17±3 and 15±4%, respectively) or lavendustin A. Tyrosine kinase does not activate ecto–5′-nucleotidase or trigger the infarct size–limiting effect of the early phase of IP in canine hearts.
Visual evoked potential: a diagnostic tool for the assessment of hepatic encephalopathy.
Authors: M L Zeneroli, G Pinelli, G Gollini, A Penne, E Messori, G Zani, E Ventura
Journal: Gut (1984)

Visual evoked potential recordings were examined in 45 liver cirrhosis patients with (n = 29) and without (n = 16) encephalopathy, in 15 normal volunteers, and in one patient with an opioid induced stupor state. Visual evoked potential parameters were classified on the basis of EEG recordings. Plasma concentrations of amino acids, octopamine, and ammonia were assayed in order to document the metabolic change of hepatic encephalopathy. Latencies and wave patterns recorded after flash stimulation differentiated the four degrees of the coma one from another according to EEG classification in the 29 patients with encephalopathy. In the group of 16 patients without clinical and EEG evidence of encephalopathy the visual potential recordings discriminated a group of patients (n = 10) in a preclinical stage of encephalopathy. Biochemical parameters and subsequent clinical observation of patients confirmed our judgement of a preclinical stage of encephalopathy. These results suggest that visual evoked potentials are a simple, suitable and objective method for differentiating the degrees of encephalopathy and for identifying the preclinical stage of encephalopathy.
Genomic Prediction of Locoregional Recurrence After Mastectomy in Breast Cancer
Authors: Skye H. Cheng, Cheng-Fang Horng, Mike West, Erich Huang, Jennifer Pittman, Mei-Hua Tsou, Holly Dressman, Chii-Ming Chen, Stella Y. Tsai, James J. Jian, Mei-Chin Liu, Joseph R. Nevins, Andrew T. Huang
Journal: Journal of Clinical Oncology (2006)

This study aims to explore gene expression profiles that are associated with locoregional (LR) recurrence in breast cancer after mastectomy.A total of 94 breast cancer patients who underwent mastectomy between 1990 and 2001 and had DNA microarray study on the primary tumor tissues were chosen for this study. Eligible patient should have no evidence of LR recurrence without postmastectomy radiotherapy (PMRT) after a minimum of 3-year follow-up (n = 67) and any LR recurrence (n = 27). They were randomly split into training and validation sets. Statistical classification tree analysis and proportional hazards models were developed to identify and validate gene expression profiles that relate to LR recurrence.Our study demonstrates two sets of gene expression profiles (one with 258 genes and the other 34 genes) to be of predictive value with respect to LR recurrence. The overall accuracy of the prediction tree model in validation sets is estimated 75% to 78%. Of patients in validation data set, the 3-year LR control rate with predictive index more than 0.8 derived from 34-gene prediction models is 91%, and predictive index 0.8 or less is 40% (P = .008). Multivariate analysis of all patients reveals that estrogen receptor and genomic predictive index are independent prognostic factors that affect LR control.Using gene expression profiles to develop prediction tree models effectively identifies breast cancer patients who are at higher risk for LR recurrence. This gene expression-based predictive index can be used to select patients for PMRT.
Assessing an outbreak of tuberculosis in an English college population
Authors: I. Abubakar, T. Matthews, D. Harmer, E. Okereke, K. Crawford, T. Hall, T. Collyns, G. Smith, A. Barrett, S. Baugh
Journal: European Respiratory Journal (2011)

Assessing an outbreak of tuberculosis in an English college populationTo the Editors:In October 2008, a sixth form college student in England, UK, who had had a cough for 2 months was diagnosed with sputum smear-positive cavitatory pulmonary tuberculosis.An investigation led to the identification of 19 cases of active tuberculosis among 2,284 students.Here, we describe the outbreak and investigation into the factors associated with active tuberculosis.
Preoperative Chemoradiation for Patients With Pancreatic Cancer: Toxicity of Endobiliary Stents
Authors: Peter W. T. Pisters, Wayne A. Hudec, Jeffrey E. Lee, Isaac Raijman, Sandeep Lahoti, Nora A. Janjan, Tyvin A. Rich, Christopher H. Crane, Renato Lenzi, Robert A. Wolff, James L. Abbruzzese, Douglas B. Evans
Journal: Journal of Clinical Oncology (2000)

PURPOSE: A recent multicenter study of preoperative chemoradiation and pancreaticoduodenectomy for localized pancreatic adenocarcinoma suggested that biliary stent–related complications are frequent and severe and may prevent the delivery of all components of multimodality therapy in many patients. The present study was designed to evaluate the rates of hepatic toxicity and biliary stent–related complications and to evaluate the impact of this morbidity on the delivery of preoperative chemoradiation for pancreatic cancer at a tertiary care cancer center. PATIENTS AND METHODS: Preoperative chemoradiation was used in 154 patients with resectable pancreatic adenocarcinoma (142 patients, 92%) or other periampullary tumors (12 patients, 8%). Patients were treated with preoperative fluorouracil (115 patients), paclitaxel (37 patients), or gemcitabine (two patients) plus concurrent rapid-fractionation (30 Gy; 123 patients) or standard-fractionation (50.4 Gy; 31 patients) radiation therapy. The incidences of hepatic toxicity and biliary stent–related complications were evaluated during chemoradiation and the immediate 3- to 4-week postchemoradiation preoperative period. RESULTS: Nonoperative biliary decompression was performed in 101 (66%) of 154 patients (endobiliary stent placement in 77 patients and percutaneous transhepatic catheter placement in 24 patients). Stent-related complications (occlusion or migration) occurred in 15 patients. Inpatient hospitalization for antibiotics and stent exchange was necessary in seven of 15 patients (median hospital stay, 3 days). No patient experienced uncontrolled biliary sepsis, hepatic abscess, or stent-related death. CONCLUSION: Preoperative chemoradiation for pancreatic cancer is associated with low rates of hepatic toxicity and biliary stent–related complications. The need for biliary decompression is not a clinically significant concern in the delivery of preoperative therapy to patients with localized pancreatic cancer.
Assessment of whether in-hospital mortality for lobectomy is a useful standard for the quality of lung cancer surgery: retrospective study
Authors: T. Treasure
Journal: BMJ (2003)

<b>Objectives</b> To calculate in-hospital mortality after lobectomy for primary lung cancer in the United Kingdom; to explore the validity of using such data to assess the quality of UK thoracic surgeons; and to investigate the relation between in-hospital mortality and the number of procedures performed by surgeons. <b>Design</b> Retrospective study. <b>Setting</b> 36 departments dealing with thoracic surgery in UK hospitals. <b>Participants</b> 4028 patients who had undergone lobectomy for primary lung cancer by one of 102 surgeons. <b>Main outcome measures</b> In-hospital mortality in relation to individual surgeons, among all patients, and among each of five groups of patients defined by the number of operations performed by the surgeon. <b>Results</b> 103 patients (2.6%, 95% confidence interval 2.1% to 3.1%) died after surgery during the same hospital admission. No significant difference was found for in-hospital mortality between the five groups. <b>Conclusions</b> The number of procedures performed by a thoracic surgeon is not related to in-hospital mortality. Reporting data on in-hospital mortality after lobectomy for primary lung cancer is a poor tool for measuring a surgeon9s performance.
Branching Enzyme Deficiency
Authors: Carmen Paradas, Hasan O. Akman, Carolina Ionete, Heather Lau, Peter N. Riskind, David E. Jones, Thomas W. Smith, Michio Hirano, Salvatore DiMauro
Journal: JAMA Neurology (2013)

The neuromuscular presentation of glycogen branching enzyme deficiency includes a severe infantile form and a late-onset variant known as adult polyglucosan body disease. Herein, we describe 2 patients with adult acute onset of fluctuating neurological signs and brain magnetic resonance imaging lesions simulating multiple sclerosis. A better definition of this new clinical entity is needed to facilitate diagnosis.To describe the clinical presentation and progression of a new intermediate variant of glycogen branching enzyme deficiency and to discuss genotype-phenotype correlations.Clinical, biochemical, morphological, and molecular study of 2 patients followed up for 6 years and 8 years at academic medical centers. The participants were 2 patients of non-Ashkenazi descent with adult acute onset of neurological signs initially diagnosed as multiple sclerosis.Clinical course, muscle and nerve morphology, longitudinal study of brain magnetic resonance imaging, and glycogen branching enzyme activity and GBE1 molecular analysis.Molecular analysis showed that one patient was homozygous (c.1544G>A) and the other patient was compound heterozygous (c.1544G>A and c.1961-1962delCA) for GBE1 mutations. Residual glycogen branching enzyme activity was 16% and 30% of normal in leukocytes. Both patients manifested acute episodes of transient neurological symptoms, and neurological impairment was mild at age 45 years and 53 years. Brain magnetic resonance imaging revealed nonprogressive white matter lesions and spinocerebellar atrophy similar to typical adult polyglucosan body disease.GBE1 mutations can cause an early adult-onset relapsing-remitting form of polyglucosan body disease distinct from adult polyglucosan body disease in several ways, including younger age at onset, history of infantile liver involvement, and subacute and remitting course simulating multiple sclerosis. This should orient neurologists toward the correct diagnosis.
Direct immunofluorescence in the diagnosis of scleroderma syndromes
Authors: R.K. Winkelmann, Francisco J. Carapeto, Robert E. Jordon
Journal: British Journal of Dermatology (1977)

Immunofluorescent study of the skin of nine patients with mesenchymal, inflammatory scleroderma (mixed connective tissue disease) revealed immunoglobulin and complement deposition at the basement membrane or within blood vessel walls. The skin specimens of ten patients with systemic scleroderma were negative for immunofluorescence. It is proposed that basement membrane or vascular (or both) immunofluorescence is an excellent means of identifying the infrequent patient who has scleroderma and myositis or lupus erythematosus in whom a corticosteroid response may occur.
Magnetic resonance for assessment of disease activity and severity in ileocolonic Crohn's disease
Authors: J. Rimola, S. Rodriguez, O. Garcia-Bosch, I. Ordas, E. Ayala, M. Aceituno, M. Pellise, C. Ayuso, E. Ricart, L. Donoso, J. Panes
Journal: Gut (2009)

Assessment of disease extension and activity is crucial to guide treatment in Crohn's disease. The objective of the current cross-sectional study was to determine the accuracy of MR for this assessment.50 patients with clinically active (n = 35) or inactive (n = 15) Crohn's disease underwent ileocolonoscopy (reference standard) and MR. T2-weighted and precontrast and postcontrast-enhanced T1-weighted sequences were acquired. Endoscopic activity was evaluated by CDEIS (Crohn's Disease Endoscopic Index of Severity); in addition endoscopic lesions were classified as absent, mild (inflammation without ulcers) or severe (presence of ulceration).The comparison of intestinal segments with absent, mild and severe inflammation demonstrated a progressive and significant (p<0.001) increase in the following MR parameters: wall thickness, postcontrast wall signal intensity, relative contrast enhancement, presence of oedema, ulcers, pseudopolyps and lymph node enlargement. Independent predictors for CDEIS in a segment were wall thickness (p = 0.007), relative contrast enhancement (p = 0.01), presence of oedema (p = 0.02) and presence of ulcers at MR (p = 0.003). There was a significant correlation (r = 0.82, p<0.001) between the CDEIS of the segment and the MR index calculated according to the logistic regression analysis coefficients. The MR index had a high accuracy for the detection of disease activity (area under the receiver operating characteristic (ROC) curve 0.891, sensitivity 0.81, specificity 0.89) and for the detection of ulcerative lesions (area under the ROC curve 0.978, sensitivity 0.95, specificity 0.91) in the colon and terminal ileum.The accuracy of MR for detecting disease activity and assessing severity brings about the possibility of using MR as an alternative to endoscopy in the evaluation of ileocolonic Crohn's disease.
Role of the Microvascular Endothelium in Progressive Renal Disease
Authors: Duk-Hee Kang, John Kanellis, Christian Hugo, Luan Truong, Sharon Anderson, Dontscho Kerjaschki, George F. Schreiner, Richard J. Johnson
Journal: Journal of the American Society of Nephrology (2002)

The role of the vascular endothelium in progressive renal disease is not well understood. This review presents evidence that progressive renal disease is characterized by a progressive loss of the microvasculature. The loss of the microvasculature correlates directly with the development of glomerular and tubulointerstitial scarring. The mechanism is mediated in part by a reduction in the endothelial proliferative response, and this impairment in capillary repair is mediated by alteration in the local expression of both angiogenic (vascular endothelial growth factor) and antiangiogenic (thrombospondin 1) factors in the kidney. The alteration in balance of angiogenic growth factors is mediated by both macrophage-associated cytokines (interleukin-1beta) and vasoactive mediators. Finally, there is intriguing evidence that stimulation of angiogenesis and/or capillary repair may stabilize renal function and slow progression and that this benefit occurs independently of effects on BP or proteinuria. Therefore, angiogenic agents may represent a novel therapeutic approach for slowing the progression of renal disease.