tbuckley/cabot-search huggingface dataset:
Impact of Expeditious Management of Perioperative Myocardial Ischemia in Patients Undergoing Isolated Coronary Artery Bypass Surgery
Authors: Piroze M. Davierwala, Alexander Verevkin, Sergey Leontyev, Martin Misfeld, Michael A. Borger, Friedrich W. Mohr
Journal: Circulation (2013)

Background— To analyze the effect of immediate treatment of perioperative myocardial ischemia (PMI) because of early graft failure or incomplete revascularization in patients undergoing coronary artery bypass grafting (CABG) surgery. Methods and Results— Between January 2004 and December 2010, 7461 patients underwent isolated CABG at our institution. All patients showing evidence of PMI (n=399; 5.3% of total) underwent emergent coronary angiography. A total of 900 grafts and 1061 distal anastomoses were examined. Two hundred fifty-five patients had 360 distal anastomoses compromised because of early graft failure or incomplete revascularization (ie, abnormal postoperative coronary angiogram). Revision CABG or percutaneous coronary intervention was performed in 130 (51.0%) and 34 (13.3%) patients with abnormal angiograms, respectively. Nonsurgical therapy was implemented in the remaining 91 patients (35.7%) with abnormal angiograms. One hundred forty-four patients had normal postoperative graft-related angiograms. In-hospital mortality was 7.3% and 2.9% in patients with and without PMI ( P &lt;0.001). In patients with PMI, in-hospital mortality was 9.4% and 3.5% in patients with abnormal and normal postoperative angiograms, respectively ( P =0.03). Significant multivariable predictors of in-hospital mortality were hemodynamic deterioration, preangiography creatine kinase-MB isoenzyme rise &gt;2× normal, and time interval between primary CABG and coronary angiography &gt;30 hours. Five-year survival in patients without PMI (85.7±0.5%) was significantly better than those with PMI and abnormal angiograms (74.9±2.9%; P &lt;0.001 log-rank). When in-hospital mortality was excluded, however, this difference in midterm survival disappeared ( P =0.9). Conclusions— PMI is associated with increased in-hospital mortality in patients undergoing isolated CABG. Expeditious management of bypass graft failure results in similar midterm survival to nonischemic patients in hospital survivors.
Pathogenesis of Lethal Cardiac Arrhythmias in <i>Mecp2</i> Mutant Mice: Implication for Therapy in Rett Syndrome
Authors: Mark D. McCauley, Tiannan Wang, Elise Mike, Jose Herrera, David L. Beavers, Teng-Wei Huang, Christopher S. Ward, Steven Skinner, Alan K. Percy, Daniel G. Glaze, Xander H. T. Wehrens, Jeffrey L. Neul
Journal: Science Translational Medicine (2011)

Rett syndrome is a neurodevelopmental disorder typically caused by mutations in methyl-CpG-binding protein 2 (MECP2) in which 26% of deaths are sudden and of unknown cause. To explore the hypothesis that these deaths may be due to cardiac dysfunction, we characterized the electrocardiograms in 379 people with Rett syndrome and found that 18.5% show prolongation of the corrected QT interval (QTc), an indication of a repolarization abnormality that can predispose to the development of an unstable fatal cardiac rhythm. Male mice lacking MeCP2 function, Mecp2(Null/Y), also have prolonged QTc and show increased susceptibility to induced ventricular tachycardia. Female heterozygous null mice, Mecp2(Null/+), show an age-dependent prolongation of QTc associated with ventricular tachycardia and cardiac-related death. Genetic deletion of MeCP2 function in only the nervous system was sufficient to cause long QTc and ventricular tachycardia, implicating neuronally mediated changes to cardiac electrical conduction as a potential cause of ventricular tachycardia in Rett syndrome. The standard therapy for prolonged QTc in Rett syndrome, β-adrenergic receptor blockers, did not prevent ventricular tachycardia in Mecp2(Null/Y) mice. To determine whether an alternative therapy would be more appropriate, we characterized cardiomyocytes from Mecp2(Null/Y) mice and found increased persistent sodium current, which was normalized when cells were treated with the sodium channel-blocking anti-seizure drug phenytoin. Treatment with phenytoin reduced both QTc and sustained ventricular tachycardia in Mecp2(Null/Y) mice. These results demonstrate that cardiac abnormalities in Rett syndrome are secondary to abnormal nervous system control, which leads to increased persistent sodium current. Our findings suggest that treatment in people with Rett syndrome would be more effective if it targeted the increased persistent sodium current to prevent lethal cardiac arrhythmias.
Autologous stem cell transplantation in a case of treatment resistant central nervous system lupus
Authors: E Trysberg
Journal: Annals of the Rheumatic Diseases (2000)

This case report describes a young woman with systemic lupus erythematosus starting at 16 years of age and giving rise to severe neurological complications including bilateral opticus neuritis and transverse myelitis. Despite heavy immunosuppression her condition steadily aggravated. At this point it was decided to perform autologous stem cell transplantation. Haematopoietic stem cells were mobilised with cyclophosphamide and granulocyte colony stimulating factor. Enrichment of CD34<sup>+</sup>cells was followed by depletion of peripheral T and B cells. The post-transplantation course was uneventful, and all the neurological deficits improved promptly during the 15 months of follow up. This is the first description of successful autologous stem cell transplantation in a case of life threatening central nervous system lupus.
Prognostic Significance of Dyspnea in Patients Referred for Cardiac Stress Testing
Authors: Aiden Abidov, Alan Rozanski, Rory Hachamovitch, Sean W. Hayes, Fatma Aboul-Enein, Ishac Cohen, John D. Friedman, Guido Germano, Daniel S. Berman
Journal: New England Journal of Medicine (2005)

Although dyspnea is a common symptom, there has been only limited investigation of its prognostic significance among patients referred for cardiac evaluation.We studied 17,991 patients undergoing myocardial-perfusion single-photon-emission computed tomography during stress and at rest. Patients were divided into five categories on the basis of symptoms at presentation (none, nonanginal chest pain, atypical angina, typical angina, and dyspnea). Multivariable analysis was used to assess the incremental prognostic value of symptom categories in predicting the risk of death from cardiac causes and from any cause. In addition, the prognosis associated with various symptoms at presentation was compared in subgroups selected on the basis of propensity analysis.After a mean (+/-SD) follow-up of 2.7+/-1.7 years, the rate of death from cardiac causes and from any cause was significantly higher among patients with dyspnea (both those previously known to have coronary artery disease and those with no known history of coronary artery disease) than among patients with other or no symptoms at presentation. Among patients with no known history of coronary artery disease, those with dyspnea had four times the risk of sudden death from cardiac causes of asymptomatic patients and more than twice the risk of patients with typical angina. Dyspnea was associated with a significant increase in the risk of death among each clinically relevant subgroup and remained an independent predictor of the risk of death from cardiac causes (P<0.001) and from any cause (P<0.001) after adjustment for other significant factors by multivariable and propensity analysis.In a large series of patients, self-reported dyspnea identified a subgroup of otherwise asymptomatic patients at increased risk for death from cardiac causes and from any cause. Our results suggest that an assessment of dyspnea should be incorporated into the clinical evaluation of patients referred for cardiac stress testing.
Transient Receptor Potential 1 Regulates Capacitative Ca2+ Entry and Ca2+ Release from Endoplasmic Reticulum in B Lymphocytes
Authors: Yasuo Mori, Minoru Wakamori, Tomoya Miyakawa, Meredith Hermosura, Yuji Hara, Motohiro Nishida, Kenzo Hirose, Akiko Mizushima, Mari Kurosaki, Emiko Mori, Kumiko Gotoh, Takaharu Okada, Andrea Fleig, Reinhold Penner, Masamitsu Iino, Tomohiro Kurosaki
Journal: The Journal of Experimental Medicine (2002)

Capacitative Ca2+ entry (CCE) activated by release/depletion of Ca2+ from internal stores represents a major Ca2+ influx mechanism in lymphocytes and other nonexcitable cells. Despite the importance of CCE in antigen-mediated lymphocyte activation, molecular components constituting this mechanism remain elusive. Here we demonstrate that genetic disruption of transient receptor potential (TRP)1 significantly attenuates both Ca2+ release-activated Ca2+ currents and inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release from endoplasmic reticulum (ER) in DT40 B cells. As a consequence, B cell antigen receptor–mediated Ca2+ oscillations and NF-AT activation are reduced in TRP1-deficient cells. Thus, our results suggest that CCE channels, whose formation involves TRP1 as an important component, modulate IP3 receptor function, thereby enhancing functional coupling between the ER and plasma membrane in transduction of intracellular Ca2+ signaling in B lymphocytes.
The dietary prevention of hepatic coma in eck fistula dogs: Ammonia and the carbohydrate to protein ratio
Authors: L. Zieve, F. J. Zieve
Journal: Hepatology (1987)

The conventional animal model of human portal systemic encephalopathy is the dog with Eck fistula. Dogs fed standard dog chow after Eck fistula manifest anorexia, weight loss, hepatic atrophy and encephalopathy. This study was done to determine the natural history of dogs undergoing Eck fistulas when adequate nutrition is maintained with a palatable diet. Twenty-four mongrel dogs were divided into four groups—Eck fistula fed standard dry dog chow (EF-SC) (n equals nine); sham-operated fed standard chow (SO-SC) (n equals five); Eck fistula fed a liquid (Isocal) diet (EF-LD), and sham-operated fed a liquid diet (SO-LD) (n equals five). Dogs were sacrificed when they had clinical signs of encephalopathy or up to 120 days after operation. EF-SC dogs had a daily caloric intake approximately 40 per cent of that of the other groups. Two EF-SC dogs died of sepsis within two weeks of the operation, the other seven became encephalopathic between 46 and 91 days (a mean of 63.6 ± 15.6). On other dogs had signs of neurologic deterioration. EF-SC dogs lost 19 ± 9 per cent body weight and the serum albumin level decreased 14.5 per cent while the other groups maintained body weight and serum albumin levels. Both EF-SC and EF-LD groups had decreased liver weight to body weight ratios (LW × 100/BW) compared with sham-operated upon dogs reflecting hepatic atrophy (1.97 ± 0.7 and 2.2 ± 0.23 versus 3.04 ± 0.85 and 3.48 ± 0.44). Results of histologic examination of the liver revealed hepatocyte atrophy, deglycogenation and lipid accumulation in EF dogs. We conclude from these data that providing dogs with Eck fistula a palatable diet prevents weight loss and malnutrition, but not hepatic atrophy. The lack of neurologic signs in well nourished dogs suggests to us that data concerning hepatic coma from the standard Eck fistula model should be interpreted with extreme caution.
Nevirapine and Efavirenz Elicit Different Changes in Lipid Profiles in Antiretroviral- Therapy-Naive Patients Infected with HIV-1
Authors: Frank van Leth, Prahpan Phanuphak, Erik Stroes, Brian Gazzard, Pedro Cahn, François Raffi, Robin Wood, Mark Bloch, Christine Katlama, John J. P Kastelein, Mauro Schechter, Robert L Murphy, Andrzej Horban, David B Hall, Joep M. A Lange, Peter Reiss
Journal: PLoS Medicine (2004)

Background Patients infected with HIV-1 initiating antiretroviral therapy (ART) containing a non-nucleoside reverse transcriptase inhibitor (NNRTI) show presumably fewer atherogenic lipid changes than those initiating most ARTs containing a protease inhibitor. We analysed whether lipid changes differed between the two most commonly used NNRTIs, nevirapine (NVP) and efavirenz (EFV). Methods and Findings Prospective analysis of lipids and lipoproteins was performed in patients enrolled in the NVP and EFV treatment groups of the 2NN study who remained on allocated treatment during 48 wk of follow-up. Patients were allocated to NVP (n = 417), or EFV (n = 289) in combination with stavudine and lamivudine. The primary endpoint was percentage change over 48 wk in high-density lipoprotein cholesterol (HDL-c), total cholesterol (TC), TC:HDL-c ratio, non-HDL-c, low-density lipoprotein cholesterol, and triglycerides. The increase of HDL-c was significantly larger for patients receiving NVP (42.5%) than for patients receiving EFV (33.7%; p = 0.036), while the increase in TC was lower (26.9% and 31.1%, respectively; p = 0.073), resulting in a decrease of the TC:HDL-c ratio for patients receiving NVP (−4.1%) and an increase for patients receiving EFV (+5.9%; p < 0.001). The increase of non-HDL-c was smaller for patients receiving NVP (24.7%) than for patients receiving EFV (33.6%; p = 0.007), as were the increases of triglycerides (20.1% and 49.0%, respectively; p < 0.001) and low-density lipoprotein cholesterol (35.0% and 40.0%, respectively; p = 0.378). These differences remained, or even increased, after adjusting for changes in HIV-1 RNA and CD4+ cell levels, indicating an effect of the drugs on lipids over and above that which may be explained by suppression of HIV-1 infection. The increases in HDL-c were of the same order of magnitude as those seen with the use of the investigational HDL-c-increasing drugs. Conclusion NVP-containing ART shows larger increases in HDL-c and decreases in TC:HDL-c ratio than an EFV-containing regimen. Based on these findings, protease-inhibitor-sparing regimens based on non-nucleoside reverse transcriptase inhibitor, particularly those containing NVP, may be expected to result in a reduced risk of coronary heart disease.
Exposure to environmental tobacco smoke and sensitisation in children
Authors: E Lannero, M Wickman, M van Hage, A Bergstrom, G Pershagen, L Nordvall
Journal: Thorax (2007)

<h3>Background:</h3> Exposure to environmental tobacco smoke (ETS) increases the risk of respiratory illness in children but data are inconclusive regarding the risk of IgE sensitisation. <h3>Objective:</h3> To elucidate whether exposure to smoking prenatally and/or postnatally is related to IgE sensitisation in children at 4 years of age. <h3>Methods:</h3> As part of a prospective birth cohort study (BAMSE), a total of 4089 families with children answered questionnaires when the child was 2 months, 1, 2 and 4 years old on environmental factors and symptoms of allergic disease. Blood collected at age 4 years from 2614 children was analysed for IgE antibodies to common inhalant and food allergens. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression with adjustments for potential confounders. <h3>Results:</h3> There was no evident association between maternal smoking during pregnancy and risk of IgE sensitisation. In contrast, a dose–response effect was found for exposure to ETS from parental smoking during the first few months of life and IgE sensitisation. There was an increased risk of sensitisation to inhalant and/or food allergens (OR<sub>adj</sub> 1.28 (95% CI 1.01 to 1.62)) among children exposed to ETS at 2 months of age. The risk appeared particularly elevated for indoor inhalant allergens, such as cat (OR<sub>adj </sub>1.96 (95% CI 1.28 to 2.99)) and for food allergens (OR<sub>adj</sub> 1.46 (95% CI 1.11 to 1.93)). The IgE sensitising effect of ETS seemed to be confined to infants of parents without allergic diseases and to ETS exposure during early infancy. <h3>Conclusions:</h3> Our data indicate that exposure in early infancy to ETS increases the risk of IgE sensitisation to indoor inhalant and food allergens.
Phase III Trial of Paclitaxel Plus Carboplatin With or Without Tirapazamine in Advanced Non–Small-Cell Lung Cancer: Southwest Oncology Group Trial S0003
Authors: Stephen K. Williamson, John J. Crowley, Primo N. Lara, Jason McCoy, Derick H.M. Lau, Robert W. Tucker, Glenn M. Mills, David R. Gandara
Journal: Journal of Clinical Oncology (2005)

Tumor hypoxia confers chemotherapy resistance. Tirapazamine is a cytotoxin that selectively targets hypoxic cells. We conducted a phase III clinical trial to determine whether the addition of tirapazamine to paclitaxel and carboplatin offered a survival advantage when used in the treatment of patients with advanced non-small-cell lung cancer (NSCLC).Of 396 patients registered, 367 eligible patients were randomly assigned to either arm 1 (n = 181), which consisted of treatment every 21 days with paclitaxel 225 mg/m2/3 h, carboplatin (area under the curve = 6), and tirapazamine 260 mg/m2 in cycle 1 (which was escalated, if tolerable, to 330 mg/m(2) in cycle 2), or arm 2 (n = 186), which consisted of paclitaxel and carboplatin as in arm 1 with no tirapazamine.Patient characteristics were similar between the two arms. There were no statistically significant differences in response rates, progression-free survival, or overall survival. Patients on arm 1 had significantly (P < .05) more abdominal cramps, fatigue, transient hearing loss, febrile neutropenia, hypotension, myalgias, and skin rash and were removed from treatment more often as a result of toxicity than patients in arm 2 (26% v 13%, respectively; P = .003). More than 40% of patients did not have the tirapazamine dose escalated, primarily because of toxicity. The trial was closed early after an interim analysis demonstrated that the projected 37.5% improvement in survival (8 v 11 months median survival) in arm 1 was unachievable (P = .003).The addition of tirapazamine to paclitaxel and carboplatin does not result in improved survival in advanced NSCLC compared with paclitaxel and carboplatin alone but substantially increases toxicity.
Disability in young people and adults one year after head injury: prospective cohort study
Authors: S. Thornhill
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To determine the frequency of disability in young people and adults admitted to hospital with a head injury and to estimate the annual incidence in the community. <b>Design:</b> Prospective, hospital based cohort study, with one year follow up of sample stratified by coma score. <b>Setting:</b> Five acute hospitals in Glasgow. <b>Subjects:</b> 2962 patients (aged 14 years or more) with head injury; 549 (71%) of the 769 patients selected for follow up participated. <b>Main outcome measures:</b> Glasgow outcome scale and problem orientated questionnaire. <b>Results:</b> Survival with moderate or severe disability was common after mild head injury (47%, 95% confidence interval 42% to 52%) and similar to that after moderate (45%, 35% to 56%) or severe injury (48%, 36% to 60%). By extrapolation from the population identified (90% of whom had mild injuries), it was estimated that annually in Glasgow (population 909 498) 1400 young people and adults are still disabled one year after head injury. <b>Conclusion:</b> The incidence of disability in young people and adults admitted with a head injury is higher than expected. This reflects the high rate of sequelae previously unrecognised in the large number of patients admitted to hospital with an apparently mild head injury.
Azithromycin and bronchiolitis obliterans syndrome after lung transplantation: is prevention better than cure?
Authors: A.J. Fisher
Journal: European Respiratory Journal (2010)

Although lung transplantation is now accepted as an established therapy for selected patients with end-stage lung disease, long-term survival after lung transplantation remains limited by the development of bronchiolitis obliterans syndrome (BOS) in >50% of recipients 1. BOS is the clinical manifestation of an inflammatory bronchiolitis associated with fibrotic remodelling of the small and medium-sized airways, and is characterised by progressive loss of allograft function with development of airflow obstruction 2, 3.

Until recently, the development of BOS was associated with an irreversible and relentless decline in lung function, which either eventually stabilised at a very low level or, in many patients, progressed to end-stage respiratory failure, accounting for the commonest cause of death after the first post-transplant year. BOS has historically been attributed to the effects of ongoing alloimmune injury as both the frequency and severity of acute rejection episodes have been associated with increased risk 4. These observations lead to the paradigm that BOS is chronic rejection of the transplanted lung and, consequently, intensification of immunosuppression was used as an attempted therapy in many affected recipients. These approaches offered, at best, a slowing in the progression of the condition in some, but also contributed to infective complications that undoubtedly added to the overall mortality risk from BOS. Over the last decade, a number of clinical trials of more intensive immunosuppressive regimes from the time of transplant or after onset of BOS have failed to impact on the incidence of BOS or regaining of lost function 5, 6. More recently, however, it has been appreciated that nonalloimmune insults to the lung allograft, such as the lung injury of primary graft dysfunction, viral and bacterial infections, and aspiration injury, also increase the risk of developing BOS 7. This suggests that cross-talk between innate …
Comparison of recombinant transforming growth factor-beta-2 and placebo as an adjunctive agent for macular hole surgery
Authors: John T Thompson, William E Smiddy, George A Williams, Raymond N Sjaarda, Harry W Flynn, Raymond R Margherio, Gary W Abrams
Journal: Ophthalmology (1998)

Objective This study aimed to compare the visual and anatomic results of macular hole surgery in eyes treated with recombinant transforming growth factor-beta-2 (TGF-β2) or placebo. Design The design was a prospective, multicenter, randomized, double-masked, placebo-controlled clinical study. Participants One hundred thirty eyes with idiopathic macular holes of 1 year or less and a refracted Early Treatment Diabetic Retinopathy Study visual acuity of 20/80 or worse were treated with 1.1 μg recombinant TGFβ2 or placebo to the macular hole after fluid-gas exchange. Intervention The effect of recombinant TGF-β2 as an adjunctive agent for macular hole surgery was evaluated. Main outcome measures Closure of the macular hole and change in visual acuity at 3 months were measured. Results The 3-month visits were completed for 120 eyes. The macular hole was closed at 3 months in 35 (61.4%) of 57 eyes treated with placebo and 49 (77.8%) of 63 eyes treated with recombinant TGF-β2 (P = 0.08). The mean visual acuity gain was +6.4 letters in eyes receiving placebo and +8.9 letters in eyes treated with recombinant TGF-β2 (P = 0.27). Visual acuity improved 2 or more lines in 23 (40.4%) of 57 eyes treated with placebo and 30 (47.6%) of 63 eyes treated with recombinant TGF-β2 (P = 0.42). Intraocular pressure elevation greater than 30 mmHg was more common 2 weeks after surgery in eyes treated with recombinant TGF-β2 (P < 0.001). Conclusions Recombinant TGF-β2 resulted in a similar proportion of successful closure of macular holes as placebo. There was no statistically significant visual acuity benefit with the use of recombinant TGF-β2 for the treatment of macular holes.
Effect of city-wide sanitation programme on reduction in rate of childhood diarrhoea in northeast Brazil: assessment by two cohort studies
Authors: Mauricio L Barreto, Bernd Genser, Agostino Strina, Ana Marlucia O Assis, Rita F Rego, Carlos A Teles, Matildes S Prado, Sheila MA Matos, Darci N Santos, Lenaldo A dos Santos, Sandy Cairncross, Maria Gloria Teixeira
Journal: The Lancet (2007)
Abstract 1788: Assessment of Genetic Risk for Hypertension in Japanese Individuals
Authors: Yumiko Yamamura, Mitsutoshi Oguri, Yoshihisa Shibata, Haruo Kamiya, Miyoshi Ohno, Kimihiko Kato, Kiyoshi Yokoi, Tetsuro Yoshida, Sachiro Watanabe, Norifumi Metoki, Kei Satoh, Yukitoshi Aoyagi, Yoshinori Nozawa, Toyoaki Murohara, Yoshiji Yamada
Journal: Circulation (2009)