tbuckley/cabot-search huggingface dataset:
Mayo Clinic Risk Score for Percutaneous Coronary Intervention Predicts In-Hospital Mortality in Patients Undergoing Coronary Artery Bypass Graft Surgery
Authors: Mandeep Singh, Bernard J. Gersh, Shuang Li, John S. Rumsfeld, John A. Spertus, Sean M. O’Brien, Rakesh M. Suri, Eric D. Peterson
Journal: Circulation (2008)

Current risk models predict in-hospital mortality after either coronary artery bypass graft surgery or percutaneous coronary interventions separately, yet the overlap suggests that the same variables can define the risks of alternative coronary reperfusion therapies. Our goal was to seek a preprocedure risk model that can predict in-hospital mortality after either percutaneous coronary intervention or coronary artery bypass graft surgery.We tested the ability of the recently validated, integer-based Mayo Clinic Risk Score (MCRS) for percutaneous coronary intervention, which is based solely on preprocedure variables (age, creatinine, ejection fraction, myocardial infarction < or = 24 hours, shock, congestive heart failure, and peripheral vascular disease), to predict in-hospital mortality among 370,793 patients in the Society of Thoracic Surgeons database undergoing isolated coronary artery bypass graft surgery from 2004 to 2006. For the Society of Thoracic Surgeons coronary artery bypass graft surgery population studied, the median age was 66 years (quartiles 1 to 3, 57 to 74 years), with 37.2% of patients > or = 70 years old. A high prevalence of comorbid conditions, including diabetes mellitus (37.1%), hypertension (80.5%), peripheral vascular disease (15.3%), and renal disease (creatinine > or = 1.4 mg/dL; 11.8%), was present. A strong association existed between the MCRS and the observed mortality in the Society of Thoracic Surgeons database. The in-hospital mortality ranged between 0.3% (95% confidence interval 0.3% to 0.4%) with a score of 0 on the MCRS and 33.8% (95% confidence interval 27.3% to 40.3%) with an MCRS score of 20 to 24. The discriminatory ability of the MCRS was moderate, as measured by the area under the receiver operating characteristic curve (C-statistic = 0.715 to 0.784 among various subgroups); performance was inferior to the Society of Thoracic Surgeons model for most categories tested.This model, which is based on 7 preprocedure risk variables, may be useful for providing patients with individualized, evidence-based estimates of procedural risk as part of the informed consent process before percutaneous or surgical revascularization.
Transmission of Streptococcus pneumoniae in an urban slum community
Authors: Joice Neves Reis, Tania Palma, Guilherme S. Ribeiro, Ricardo M. Pinheiro, Cassio Tâmara Ribeiro, Soraia Machado Cordeiro, H.P. da Silva Filho, Monica Moschioni, Terry A. Thompson, Brian Spratt, Lee W. Riley, Michele A. Barocchi, Mitermayer G. Reis, Albert I. Ko
Journal: Journal of Infection (2008)
Age-Associated Defects in EphA2 Signaling Impair the Migration of Human Cardiac Progenitor Cells
Authors: Polina Goichberg, Ramaswamy Kannappan, Maria Cimini, Yingnan Bai, Fumihiro Sanada, Andrea Sorrentino, Sergio Signore, Jan Kajstura, Marcello Rota, Piero Anversa, Annarosa Leri
Journal: Circulation (2013)

Aging negatively impacts on the function of resident human cardiac progenitor cells (hCPCs). Effective regeneration of the injured heart requires mobilization of hCPCs to the sites of damage. In the young heart, signaling by the guidance receptor EphA2 in response to the ephrin A1 ligand promotes hCPC motility and improves cardiac recovery after infarction.We report that old hCPCs are characterized by cell-autonomous inhibition of their migratory ability ex vivo and impaired translocation in vivo in the damaged heart. EphA2 expression was not decreased in old hCPCs; however, the elevated level of reactive oxygen species in aged cells induced post-translational modifications of the EphA2 protein. EphA2 oxidation interfered with ephrin A1-stimulated receptor auto-phosphorylation, activation of Src family kinases, and caveolin-1-mediated internalization of the receptor. Cellular aging altered the EphA2 endocytic route, affecting the maturation of EphA2-containing endosomes and causing premature signal termination. Overexpression of functionally intact EphA2 in old hCPCs corrected the defects in endocytosis and downstream signaling, enhancing cell motility. Based on the ability of phenotypically young hCPCs to respond efficiently to ephrin A1, we developed a novel methodology for the prospective isolation of live hCPCs with preserved migratory capacity and growth reserve.Our data demonstrate that the ephrin A1/EphA2 pathway may serve as a target to facilitate trafficking of hCPCs in the senescent myocardium. Importantly, EphA2 receptor function can be implemented for the selection of hCPCs with high therapeutic potential, a clinically relevant strategy that does not require genetic manipulation of stem cells.
Induction of carbonic anhydrase I isozyme precedes the globin synthesis during erythropoiesis in K562 cells
Authors: Takahito Kondo, Hiroshi Isobe, Yoshikazu Kawakami, Masaharu Sakai, Shinzou Nishi, Naoyuki Taniguchi
Journal: American Journal of Hematology (1991)

Induction of carbonic anhydrase isozyme I (CA-I) by erythropoietin or hemin was investigated using erythroleukemia (K562) cells. Immunological estimation and purification of carbonic anhydrases showed that untreated K562 cells contained only carbonic anhydrase isozyme II(CA-II), while incubation of the cells with 2 units of erythropoietin (EP) per ml of the incubation medium or with 50 microM hemin resulted in the induction of CA-I. The purified CA-I induced in K562 cells was enzymatically and immunologically identical to that from mature erythrocytes. Flow cytometric analysis showed that incubation of K562 cells with EP as well as hemin induced CA-I at the 3rd h, while alpha-globin was detected at the 8th h. Northern blot analysis of CA-I mRNA using a cloned genomic DNA as a probe showed that mRNA of CA-I was induced by EP. These results suggest that induction of CA-I is regulated at the transcriptional level during developmental changes of erythroid cells, and that CA-I may play a physiologically important role during erythroid differentiation.
Pigmented lesions on the palms and soles during PUVA therapy
Authors: R.A. Logan, J.S.C. English, N.P. Smith
Journal: British Journal of Dermatology (1985)

Pigmented skin lesions due to PUVA are well recognized. They include freckles, mottled skin, naevus spilus‐like lesions and ‘PUVA lentigines’ (Kietzmann & Christophers, 1984). The PUVA lentigo appears to be common, occurring in up to 53% of patients (Rhodes, Stern & Melski, 1983). These discrete brown macules, 2–5 mm in diameter, may become very widespread, particularly in those patients who have had many PUVA treatments. They tend to spare the face and have not previously been reported on the palms or soles. We have now seen three female patients who have developed pigmented lesions on their palms (and in one case also on the sole) whilst receiving long‐term oral PUVA therapy for psoriasis. The lesions were of two types: ill‐defined light grey‐brown macules (histologically a freckle, with no increase in number of basal melanocytes), and discrete dark brown macules. The latter showed focal proliferation of dendritic melanocytes at the dermo‐epidermal junction, with increased pigmentation throughout the epidermis and also in the superficial dermis. These lesions developed after a minimum of 70 PUVA treatments (over 18 months) in one case, but only appeared after 5 years' PUVA (330 treatments) in another. Ultrastructural studies (Rhodes, Harrist & Momtaz, 1983) have demonstrated that the melanocytes in PUVA lentigines may show cytological atypia. PUVA lentigines may also persist for up to 2 years (and probably longer) after stopping PUVA. Patients undergoing prolonged PUVA therapy to the palms and soles should be warned about the possibility of developing pigmented lesions which may persist after cessation of therapy.
Increased Cardiac Expression of Tissue Inhibitor of Metalloproteinase-1 and Tissue Inhibitor of Metalloproteinase-2 Is Related to Cardiac Fibrosis and Dysfunction in the Chronic Pressure-Overloaded Human Heart
Authors: Stephane Heymans, Blanche Schroen, Pieter Vermeersch, Hendrik Milting, Fangye Gao, Astrid Kassner, Hilde Gillijns, Paul Herijgers, Willem Flameng, Peter Carmeliet, Frans Van de Werf, Yigal M. Pinto, Stefan Janssens
Journal: Circulation (2005)

Background— Alterations in the balance of matrix metalloproteinases (MMPs) and their specific tissue inhibitors (TIMPs) are involved in left ventricular (LV) remodeling. Whether their expression is related to interstitial fibrosis or LV dysfunction in patients with chronic pressure overload–induced LV hypertrophy, however, is unknown. Methods and Results— Therefore, cardiac biopsies were taken in 36 patients with isolated aortic stenosis (AS) and in 29 control patients without LV hypertrophy. Microarray analysis revealed significantly increased mRNA expression of collagen types I, III, and IV and transcripts involved in collagen synthesis, including procollagen endopeptidase and lysine and proline hydroxylases, in AS compared with control patients. Collagen deposition was greater in AS than in control patients and was most pronounced in AS patients with severe diastolic dysfunction. Cardiac mRNA expression of TIMP-1 and TIMP-2 was significantly increased in AS compared with control patients (mRNA transcript levels normalized to GAPDH: TIMP-1, 0.67±0.1 in AS versus 0.37±0.08 in control patients; TIMP-2, 9.5±2.6 in AS versus 1.6±0.4 in control patients; P &lt;0.05 for both) but did not differ significantly for MMP-1, -2, or -9. Cardiac TIMP-1 and -2 transcripts were significantly related to the degree of interstitial fibrosis and proportional to diastolic dysfunction in AS patients. Conclusions— Cardiac expression of TIMP-1 and TIMP-2 is significantly increased in chronic pressure-overloaded human hearts compared with controls and is related to the degree of interstitial fibrosis.
The high-resolution CT findings predict the incidence of ventilator-associated pneumonia and mortality in patients with acute respiratory distress syndrome
Authors: Makoto Takaki, Kazuya Ichikado, Moritaka Suga, Masakazu Yoshioka
Journal: European Respiratory Journal (2013)

Background: Patients with acute respiratory distress syndrome (ARDS) are susceptible to ventilator-associated pneumonia (VAP) and are associated with high mortality.  Aims and objectives: To make clear the clinical predictors of VAP and mortality in patients with ARDS.  Methods: We conducted a prospective observational cohort study in 112 patients (67 males) who admitted to our hospital between October, 2004, and July, 2012, that met the Berlin Definition of ARDS. The primary endpoint was 60-day mortality. The secondary endpoint was the incidence of VAP. The high-resolution computed tomography (HRCT) score was obtained according to the degree of fibroproliferative changes by a previously published method.  Results: 60-day mortality is 42.9%. The HRCT score is significantly associated with 60-day mortality in multiple logistic regression analysis (OR 1.05; 95% CI 1.03-1.08; p  Conclusions: The HRCT score is a good predictor of mortality and the incidence of VAP.
Gastric emptying of a liquid nutrient meal in the critically ill: relationship between scintigraphic and carbon breath test measurement
Authors: M. J. Chapman, L. K. Besanko, C. M. Burgstad, R. J. Fraser, M. Bellon, S. O'Connor, A. Russo, K. L. Jones, K. Lange, N. Q. Nguyen, F. Bartholomeusz, B. Chatterton, M. Horowitz
Journal: Gut (2011)

<h3>Objective</h3> It is assumed that delayed gastric emptying (GE) occurs frequently in critical illness; however, the prevalence of slow GE has not previously been assessed using scintigraphy. Furthermore, breath tests could potentially provide a convenient method of quantifying GE, but have not been validated in this setting. The aims of this study were to (i) determine the prevalence of delayed GE in unselected, critically ill patients and (ii) evaluate the relationships between GE as measured by scintigraphy and carbon breath test. <h3>Design</h3> Prospective observational study. <h3>Setting</h3> Mixed medical/surgical intensive care unit. <h3>Patients</h3> 25 unselected, mechanically ventilated patients (age 66 years (49–72); and 14 healthy subjects (age 62 years (19–84)). <h3>Interventions</h3> GE was measured using scintigraphy and <sup>14</sup>C-breath test. A test meal of 100 ml Ensure (standard liquid feed) labelled with <sup>14</sup>C octanoic acid and <sup>99m</sup>Technetium sulphur colloid was placed in the stomach via a nasogastric tube. <h3>Main outcome measures</h3> Gastric ‘meal’ retention (scintigraphy) at 60, 120, 180 and 240 min, breath test t<sub>50</sub> (BTt<sub>50</sub>), and GE coefficient were determined. <h3>Results</h3> Of the 24 patients with scintigraphic data, GE was delayed at 120 min in 12 (50%). Breath tests correlated well with scintigraphy in both patients and healthy subjects (% retention at 120 min vs BTt<sub>50</sub>; r<sup>2</sup>=0.57 healthy; r<sup>2</sup>=0.56 patients; p≤0.002 for both). <h3>Conclusions</h3> GE of liquid nutrient is delayed in approximately 50% of critically ill patients. Breath tests correlate well with scintigraphy and are a valid method of GE measurement in this group.
Extraosseous Osteosarcoma: Response to Treatment and Long-Term Outcome
Authors: S. A. Ahmad
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To evaluate the clinicopathologic features of extraosseous osteosarcoma (EOO), a rare soft tissue form of osteosarcoma, and to examine its response to multimodality therapy. PATIENTS AND METHODS: The medical records of all patients with EOO evaluated at The University of Texas M.D. Anderson Cancer Center between 1960 and 1999 were reviewed for clinicopathologic factors, treatment, and outcome. RESULTS: Sixty consecutive patients with EOO were identified, including 38 patients with localized (American Joint Committee on Cancer stages I to III) disease. The majority of patients presented with T2 tumors (n = 35, 58%), and 90% of tumors were located beneath the investing fascia. Twenty-seven patients with measurable and assessable disease were treated with doxorubicin-based chemotherapy (median doxorubicin starting dose, 75 mg/m2; median number of cycles, four). The overall response rate was 19%, with two complete and three partial responses; one (6%) of 18 doxorubicin-treated patients who underwent subsequent surgery had a pathologic complete response. For the subset of 30 patients with localized disease treated at M.D. Anderson, the 5-year actuarial local recurrence–free, distant recurrence–free, event-free, and disease-specific survival rates were 82% (95% confidence interval [CI], 70% to 98%), 64% (95% CI, 43% to 93%), 47% (95% CI, 30% to 70%), and 46% (95% CI, 26% to 80%), respectively. CONCLUSION: EOO should be considered clinically and therapeutically distinct from osseous osteosarcoma. Radiographic response rates and pathologic complete response rates to doxorubicin-based systemic therapy are low.
Evolutionary Perspectives on the Obesity Epidemic: Adaptive, Maladaptive, and Neutral Viewpoints
Authors: John R. Speakman
Journal: Annual Review of Nutrition (2013)

The prevalence of obesity in modern societies has two major contributory factors—an environmental change that has happened in historical times and a genetic predisposition that has its origins in our evolutionary history. Understanding both aspects is complex. From an evolutionary perspective, three different types of explanation have been proposed. The first is that obesity was once adaptive and enabled us to survive (or sustain fecundity) through periods of famine. People carrying so-called thrifty genes that enabled the efficient storage of energy as fat between famines would be at a selective advantage. In the modern world, however, people who have inherited these genes deposit fat in preparation for a famine that never comes, and the result is widespread obesity. The key problem with this, and any other adaptive scenario, is to understand why, if obesity was historically so advantageous, many people did not inherit these thrifty genes and in modern society are able to remain slim, despite the environmental change favoring fat storage. The second type of explanation is that obesity is not adaptive and may never even have existed in our evolutionary past, but it is favored today as a maladaptive by-product of positive selection on some other trait. An example of this type of explanation is the suggestion that obesity results from variation in brown adipose tissue thermogenesis. Finally, a third class of explanation is that most mutations in the genes that predispose us to obesity are neutral and have been drifting over evolutionary time—so-called drifty genes, leading some individuals to be obesity prone and others obesity resistant. In this article, I review the current evidence for and against these three different scenarios and conclude that the thrifty gene hypothesis is untenable but the other two ideas may provide a cogent explanation of the modern obesity phenomenon.
HIV treatment should be free for everyone in Britain, MPs say
Authors: Fay evan Emmerik
Journal: BMJ (2005)

HIV should be reclassified as a sexually transmitted infection so that treatment would be free to all patients, as it is for other such infections, MPs said this week.

A report on sexual health and HIV services by the House of Commons health select committee said people entitled to HIV treatment were being refused it because doctors were confused over who was eligible under last year's tightening up of the 12 month residency rule. This rule …
Open-Label Single-Arm Phase Iv Study to Assess the Efficacy and Safety of Afatinib as Second-Line Therapy for Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) Harbouring Common Epidermal Growth Factor Receptor (EGFR) Mutations (DEL19 AND/OR L858R) Who Have Failed First-Line Treatment with Platinum-Based Chemotherapy
Authors: S. Thongprasert, H. Jones, A. Cseh, R.M. Gaafar
Journal: Annals of Oncology (2015)
Duration of heart failure and the risk of atrial fibrillation: different mechanisms at different times?
Authors: A. C. Rankin, A. J. Workman
Journal: Cardiovascular Research (2009)

Chronic heart failure increases the risk of atrial fibrillation (AF), with the prevalence of AF paralleling the severity of heart failure.1 Factors that underlie this increased susceptibility to AF may include electrical, structural, and neurohumoral changes.2 In AF, it is recognized that atrial electrophysiological remodelling occurs and contributes to the perpetuation of the arrhythmia, most notably the decrease of effective refractory period (ERP) which predisposes to re-entry by shortening the wavelength. Does heart failure cause similar changes in atrial electrophysiology that predispose to the arrhythmia?

An extensively studied dog model, in which heart failure was induced by rapid ventricular pacing, has suggested not: atrial electrophysiological changes were either absent, or were in the opposite direction, with prolongation of the action potential duration (APD).3,4 Susceptibility to induced AF was increased, but this was more related to structural changes, in particular increased fibrosis,5 than electrophysiological properties. In contrast, our recent study of human right atrial isolated myocytes6 found that left ventricular (LV) systolic dysfunction was associated with electrophysiological changes—decreased APD and shortened refractoriness—which would predispose to AF, contrary to the findings in the dog model.

Sridhar et al. 7 shed some light on this discrepancy, indicating that the key factor may be the duration of heart failure. The main methodological difference in the dog … 

*Corresponding author. Tel: +44 141 211 4833; fax: +44 141 552 4683; E-mail address : acr1a{at}clinmed.gla.ac.uk
Blockage of Tubular Epithelial to Myofibroblast Transition by Hepatocyte Growth Factor Prevents Renal Interstitial Fibrosis
Authors: Junwei Yang, Youhua Liu
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Activation of α-smooth muscle actin–positive myofibroblast cells is a key event in the progression of chronic renal diseases that leads to end-stage renal failure. Although the origin of these myofibroblasts in the kidney remains uncertain, emerging evidence suggests that renal myofibroblasts may derive from tubular epithelial cells by a process of epithelial to mesenchymal transition. It was demonstrated that hepatocyte growth factor (HGF) exhibited a remarkable ability to block this phenotypic transition both in vitro and in vivo. HGF abrogated the α-smooth muscle actin expression and E-cadherin depression triggered by transforming growth factor-β1 in tubular epithelial cells in a dose-dependent manner. HGF also blocked morphologic transformation of tubular epithelial cells and inhibited the expression and extracellular deposition of fibronectin. In a mouse model of renal fibrosis disease induced by unilateral ureteral obstruction, transforming growth factor-β type I receptor expression was specifically increased in renal tubules, and myofibroblastically phenotypic transition of the tubules was evident in vivo. Remarkably, injections of exogenous HGF blocked myofibroblast activation and drastically prevented renal interstitial fibrosis in the obstructed kidneys. These results suggest that tubular epithelial to myofibroblast conversion may play an important role in the pathogenesis of renal fibrosis and that blocking this phenotypic transition could provide a novel therapeutic strategy for the treatment of fibrotic diseases.
2-Deoxy-<scp>d</scp>-glucose Increases the Efficacy of Adriamycin and Paclitaxel in Human Osteosarcoma and Non-Small Cell Lung Cancers <b> <i>In Vivo</i> </b>
Authors: Gregory Maschek, Niramol Savaraj, Waldemar Priebe, Paul Braunschweiger, Kara Hamilton, George F. Tidmarsh, Linda R. De Young, Theodore J. Lampidis
Journal: Cancer Research (2004)

Abstract Slow-growing cell populations located within solid tumors are difficult to target selectively because most cells in normal tissues also have low replication rates. However, a distinguishing feature between slow-growing normal and tumor cells is the hypoxic microenvironment of the latter, which makes them extraordinarily dependent on anaerobic glycolysis for survival. Previously, we have shown that hypoxic tumor cells exhibit increased sensitivity to inhibitors of glycolysis in three distinct in vitro models. Based on these results, we predicted that combination therapy of a chemotherapeutic agent to target rapidly dividing cells and a glycolytic inhibitor to target slow-growing tumor cells would have better efficacy than either agent alone. Here, we test this strategy in vivo using the glycolytic inhibitor 2-deoxy-d-glucose (2-DG) in combination with Adriamycin (ADR) or paclitaxel in nude mouse xenograft models of human osteosarcoma and non-small cell lung cancer. Nude mice implanted with osteosarcoma cells were divided into four groups as follows: (a) untreated controls; (b) mice treated with ADR alone; (c) mice treated with 2-DG alone; or (d) mice treated with a combination of ADR + 2-DG. Treatment began when tumors were either 50 or 300 mm3 in volume. Starting with small or large tumors, the ADR + 2-DG combination treatment resulted in significantly slower tumor growth (and therefore longer survival) than the control, 2-DG, or ADR treatments (P &amp;lt; 0.0001). Similar beneficial effects of combination treatment were found with 2-DG and paclitaxel in the MV522 non-small cell lung cancer xenograft model. In summary, the treatment of tumors with both the glycolytic inhibitor 2-DG and ADR or paclitaxel results in a significant reduction in tumor growth compared with either agent alone. Overall, these results, combined with our in vitro data, provide a rationale for initiating clinical trials using glycolytic inhibitors in combination with chemotherapeutic agents to increase their therapeutic effectiveness.