tbuckley/cabot-search huggingface dataset:
Effects of Work Loads Applied at Various Times in the Cardiac Cycle of the Isolated Dog Heart
Authors: NORMAN J. ZEIG, NANCY M. BUCKLEY, EREST P. PORTER
Journal: Circulation Research (1961)

Effects of work loads imposed at various times in the cardiac cycle were studied in isolated left ventricle preparations of dog hearts. In six preparations, resistance loads were applied briefly at times in ventricular systole; in six, volume loads were applied briefly at times in ventricular diastole; in six, experimental aortic regurgitation was produced. Simultaneous recorc1s of left ventricular and aortic pressures and electrocardiograms were used to cletermilie the subdivisions of the cardiac cycle and to measure the rates of isometric contraction and relaxation for evaluation of changes in ventricular contractility. The results of many observations indicated that the rates of isometric ventricular contraction and relaxation were not fixed by prior events, that contraction and relaxation could be altered independently, and that aortic regurgitation loaded the left ventricle at a time critical for its relaxation. Accommodation to aortic regurgitation included maintenance of contractility without diastolic left ventricular pressure rise; failure of accommodation was characterized by loss of contractility at high diastolic ventricular pressure.
If Children Understand Drawing Straws and Flipping Coins, Research Participants Can Understand Randomization
Authors: Jeremy Howick
Journal: The American Journal of Bioethics (2009)

"If Children Understand Drawing Straws and Flipping Coins, Research Participants Can Understand Randomization." The American Journal of Bioethics, 9(2), pp. 19–20 Acknowledgment This commentary was written while I was a recipient of a National Institute of Health Research Post-Doctoral bursary from the Department of Primary Health Care (Oxford, 2007–8) and an MRC/ESRC Interdisciplinary Postdoctoral Fellowship (no. G0800055).
Genetics of age at menarche: a systematic review
Authors: Volodymyr Dvornyk, None Waqar-ul-Haq
Journal: Human Reproduction Update (2012)

Menarche is the first menstrual period of a girl at puberty. The timing of menarche is important for health in later life. Age at menarche is a complex trait and has a strong genetic component. This review summarizes the results of the genetic studies of age at menarche conducted to date, highlights existing problems in this area and outlines prospects of future studies on genetic factors for the trait. PubMed and Google Scholar were searched until May 2011 using the keywords: 'menarche', 'puberty' and 'age at menarche' in combination with the keywords 'polymorphism', 'candidate gene', 'genome-wide association study' and 'linkage'. Our search yielded 170 papers, 35 of which were selected for further analysis. Several large-scale genome-wide association studies along with a powerful meta-analysis of their aggregated data identified about 50 candidate genes for the trait. Some genes were replicated in different studies of Caucasians (e.g. LIN28B, TMEM38B) or in different ethnicities (e.g. SPOCK, RANK and RANKL). However, despite the large volume of results obtained, there is a huge gap in relevant data on ethnic groups other than Caucasians. The reviewed studies laid a solid basis for future research on genetics of age at menarche. However, as yet specific genes for this trait have not been identified consistently in all ethnicities and types of studies. We suggest expanding the research to different ethnicities and propose several methodologies to increase the efficiency of studies in this area, including a systems approach, which combines existing high-throughput methods in a single pipeline.
A New Prognostic Score for Survival of Patients With Chronic Myeloid Leukemia Treated With Interferon Alfa Writing Committee for the Collaborative CML Prognostic Factors Project Group
Authors: Joerg Hasford, Markus Pfirrmann, Rüdiger Hehlmann, Norman C. Allan, Michele Baccarani, Johanna C. Kluin-Nelemans, Guiliana Alimena, Juan Luis Steegmann, Hassan Ansari
Journal: JNCI Journal of the National Cancer Institute (1998)

Interferon alfa is a conservative and widely used alternative to bone marrow transplantation in treatment of patients with early chronic myeloid leukemia (CML). A meta-analysis was conducted to develop a reliable prognostic scoring system for estimation of survival of patients with CML treated with interferon alfa.Patients treated in prospective studies, including major randomized trials, were separated into learning and validation samples. Cox regression analysis and the minimum P-value approach were used to identify prognostic factors for patient survival and to discover groups in the learning sample with the greatest differences in survival. These findings were then validated by applying the new scoring system to patients in the validation sample.We collected data on 1573 patients who were participants in 14 studies involving 12 institutions; 1303 patients (learning sample, n = 981; validation sample, n = 322) were eligible for inclusion in this analysis, and their median survival time was 69 months (range, 1-117 months). Because two previously described prognostic scoring systems failed to discriminate risk groups satisfactorily, we developed a new scoring system that utilizes the following covariates: age, spleen size, blast count, platelet count, eosinophil count, and basophil count. Among 908 patients with complete data in the learning sample, three distinct risk groups were identified (median survival times of 98 months [n = 369; 40.6%], 65 months [n = 406; 44.7%], or 42 months [n = 133;14.6%]; two-sided logrank test, P< or =.0001). The ability of the new scoring system to discriminate these risk groups was confirmed by analysis of 285 patients with complete data in the validation sample (two-sided logrank test, P = .0002).A new prognostic scoring system for estimating survival of patients with CML treated with interferon alfa has been developed and validated through use of a large dataset.
RETRACTED: Molecular forms of HMGB1 and keratin-18 as mechanistic biomarkers for mode of cell death and prognosis during clinical acetaminophen hepatotoxicity
Authors: Daniel J. Antoine, Rosalind E. Jenkins, James W. Dear, Dominic P. Williams, Mitchell R. McGill, Matthew R. Sharpe, Darren G. Craig, Kenneth J. Simpson, Hartmut Jaeschke, B. Kevin Park
Journal: Journal of Hepatology (2012)
Does Administration Order of Sequential Fec- Docetaxel As Adjuvant Chemotherapy for Breast Cancer Affect on the Toxicities? : a Retrospective Analysis from a Single-Center
Authors: T. Miyaki, H. Tsujimura, K. Kumagai, R. Nakamura, A. Yoshii, Y. Okubo, T. Iwase, A. Nakagawa, N. Yamamoto
Journal: Annals of Oncology (2014)
Impact of Proteinuria and Glomerular Filtration Rate on Risk of Thromboembolism in Atrial Fibrillation
Authors: Alan S. Go, Margaret C. Fang, Natalia Udaltsova, Yuchiao Chang, Niela K. Pomernacki, Leila Borowsky, Daniel E. Singer
Journal: Circulation (2009)

Atrial fibrillation (AF) substantially increases the risk of ischemic stroke, but this risk varies among individual patients with AF. Existing risk stratification schemes have limited predictive ability. Chronic kidney disease is a major cardiovascular risk factor, but whether it independently increases the risk for ischemic stroke in persons with AF is unknown.We examined how chronic kidney disease (reduced glomerular filtration rate or proteinuria) affects the risk of thromboembolism off anticoagulation in patients with AF. We estimated glomerular filtration rate using the Modification of Diet in Renal Disease equation and proteinuria from urine dipstick results found in laboratory databases. Patient characteristics, warfarin use, and thromboembolic events were ascertained from clinical databases, with validation of thromboembolism by chart review. During 33,165 person-years off anticoagulation among 10,908 patients with AF, we observed 676 incident thromboembolic events. After adjustment for known risk factors for stroke and other confounders, proteinuria increased the risk of thromboembolism by 54% (relative risk, 1.54; 95% CI, 1.29 to 1.85), and there was a graded, increased risk of stroke associated with a progressively lower level of estimated glomerular filtration rate compared with a rate > or =60 mL x min(-1) x 1.73 m(-2): relative risk of 1.16 (95% CI, 0.95 to 1.40) for estimated glomerular filtration rate of 45 to 59 mL x min(-1) x 1.73 m(-2) and 1.39 (95% CI, 1.13 to 1.71) for estimated glomerular filtration rate <45 mL x min(-1) x 1.73 m(-2) (P=0.0082 for trend).Chronic kidney disease increases the risk of thromboembolism in AF independently of other risk factors. Knowing the level of kidney function and the presence of proteinuria may improve risk stratification for decision making about the use of antithrombotic therapy for stroke prevention in AF.
Achieving Board Certification in Psychiatry: A Cohort Study
Authors: Dorthea Juul, James H. Scully, Stephen C. Scheiber
Journal: American Journal of Psychiatry (2003)

The purpose of this study was to track the progress of a cohort of graduates of psychiatry residency training programs in achieving certification by the American Board of Psychiatry and Neurology (ABPN). These data provide a detailed picture of how recent graduates perform on the ABPN's examinations.The subjects for this study were the 739 new candidates who sat for the part I examination in fall 1994. The cohort's performance on the part I and part II examinations was analyzed, as was the relationship between performance on the two examinations.Approximately 8 years after their first attempt at the part I examination, 85% of the cohort were certified, and 15% were not. The majority passed both the part I and part II examinations on the first attempt. Those who passed part I on the first attempt were more likely than those who failed to pass part II on the first attempt. Of the 627 who were certified at follow-up, 199 (32%) were also certified in one subspecialty, and 29 (5%) were certified in two, for a total of 257 subspecialty certificates.The results of this study suggest that most recent graduates of residency training programs who attempt the ABPN process are likely to become board certified, and the majority will do so by passing both components on the first attempt.
680 INCORPORATION OF 6-BROMOHEXANOIC ACID (6BH) INTO CELLULAR PYRUVATE DEHYDROGENASE COMPLEX (PDC): FURTHER EVIDENCE FOR GENERATION OF AN AUTOIMMUNOGENIC NEOANTIGEN IN PRIMARY BILIARY CIRRHOSIS (PBC)
Authors: J. Palmer, H. Walden, J. Kirby, D. Jones
Journal: Journal of Hepatology (2009)
Questionable research and marketing of a combination drug for smoker’s lungs
Authors: Peter Christian Gøtzsche
Journal: Journal of the Royal Society of Medicine (2014)

However, nowhere in the 15-page trial report was the correct factorial analysis to be found, and the abstract gave the readers the clear impression that the combination was better than any of its components 1 : The hazard ratio for death in the combination-ther- apy group, as compared with the placebo group, was 0.825 (95% confidence interval (CI), 0.681 to 1.002; p ¼ 0.052, adjusted for the interim analyses), corres- ponding to ... a reduction in the risk of death of 17.5%. The mortality rate for salmeterol alone or fluticasone propionate alone did not differ signifi- cantly from that for placebo.
Mechanical Reperfusion in Patients With Acute Myocardial Infarction Presenting More Than 12 Hours From Symptom Onset&lt;SUBTITLE&gt;A Randomized Controlled Trial&lt;/SUBTITLE&gt;
Authors: Albert Schömig
Journal: JAMA (2005)

No specifically designed studies have addressed the role of primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction (STEMI) presenting more than 12 hours after symptom onset. Current guidelines do not recommend reperfusion treatment in these patients.To assess whether an immediate invasive treatment strategy is associated with a reduction of infarct size in patients with acute STEMI, presenting between 12 and 48 hours after symptom onset, vs a conventional conservative strategy.International, multicenter, open-label, randomized controlled trial conducted from May 23, 2001, to December 15, 2004, of 365 patients aged 18 to 80 years without persistent symptoms admitted with the diagnosis of acute STEMI between 12 and 48 hours after symptom onset.Random assignment to either an invasive strategy (n=182) based predominantly on coronary stenting with abciximab or a conventional conservative treatment strategy (n=183).The primary end point was final left ventricular infarct size according to single-photon emission computed tomography study with technetium Tc 99m sestamibi performed between 5 and 10 days after randomization in 347 patients (95.1%). Secondary end points included composite of death, recurrent MI, or stroke at 30 days.The final left ventricular infarct size was significantly smaller in patients assigned to the invasive group (median, 8.0%; interquartile range [IQR], 2.0%-15.8%) vs those assigned to the conservative group (median, 13.0%; IQR, 3.0%-27.0%; P<.001). The mean difference in final left ventricular infarct size between the invasive and conservative groups was -6.8% (95% confidence interval [CI], -10.2% to -3.5%). The secondary end points of death, recurrent MI, or stroke at 30 days occurred in 8 patients in the invasive group (4.4%) and 12 patients in the conservative group (6.6%) (relative risk, 0.67; 95% CI, 0.27-1.62; P = .37).An invasive strategy based on coronary stenting with adjunctive use of abciximab reduces infarct size in patients with acute STEMI without persistent symptoms presenting 12 to 48 hours after symptom onset.
Treatment of pancreatic cancer with a combination of irinotecan (CPT-11) and gemcitabine: a multicenter phase II study by the Greek Cooperative Group for Pancreatic Cancer
Authors: G.P. Stathopoulos, S.K. Rigatos, M.A. Dimopoulos, T. Giannakakis, G. Foutzilas, C. Kouroussis, D. Janninis, G. Aravantinos, N. Androulakis, S. Agelaki, J.G. Stathopoulos, V. Georgoulias
Journal: Annals of Oncology (2003)
Physical disability in rheumatoid arthritis is associated with cartilage damage rather than bone destruction
Authors: D. Aletaha, J. Funovits, J. S. Smolen
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> Joint destruction in rheumatoid arthritis is comprised of cartilage and bone damage, which can be evaluated radiographically separately by the joint space narrowing (JSN) and erosion (ERO) scores. It is currently unclear to which extent these components affect irreversible functional disability. The aim of the present work was to determine these contributions. <h3>Methods</h3> Data, kindly provided by the sponsors, was evaluated from several randomised controlled clinical trials on adalimumab, etanercept, infliximab and leflunomide. Patients who reached stringent remission according to the Simplified Disease Activity Index (SDAI≤3.3) were extracted to eliminate the activity related (ie, reversible) component of disability. In these patients, residual Health Assessment Questionnaire Disability Index (HAQ-DI) score at the time of remission (to reflect the level of 'irreversible' disability) was determined and related to baseline measures of ERO and JSN scores univariately, by stratification and in adjusted regression models. <h3>Results</h3> A total of 748 patients who achieved a state of remission were analysed (16.3% of the total pooled population of 4602 patients). In the univariate analyses, mean residual HAQ-DI values in remission were significantly larger in higher tertiles of JSN and ERO (ERO: 0.21, 0.25, 0.35; JSN: 0.19, 0.24, 0.39; p&lt;0.001 for both). In stratified analyses, mean residual HAQ-DI scores were larger in higher tertiles of JSN within the first tertile of ERO (0.18, 0.25, 0.29; p=0.05), as well as the second (0.21, 0.24, 0.29; p=0.19) and the third (0.12, 0.23, 0.42; p&lt;0.001). In contrast, there was no such trend across ERO tertiles within the first JSN tertile (0.18, 0.21, 0.12; p=0.99) and the second tertile (0.25, 0.24, 0.23; p=0.77), and only marginally within the third tertile of JSN (0.29, 0.29, 0.42; p=0.07). Adjusted multivariate regression models supported the significant association of JSN on residual disability. <h3>Conclusions</h3> Cartilage damage appears to be the more clearly associated with irreversible physical disability than bony damage. These data suggest that particular attention should be given to therapeutic interference with cartilage destruction.
Cardiac macrophage migration inhibitory factor inhibits JNK pathway activation and injury during ischemia/reperfusion
Authors: Dake Qi, Xiaoyue Hu, Xiaohong Wu, Melanie Merk, Lin Leng, Richard Bucala, Lawrence H. Young
Journal: Journal of Clinical Investigation (2009)

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that also modulates physiologic cell signaling pathways. MIF is expressed in cardiomyocytes and limits cardiac injury by enhancing AMPK activity during ischemia. Reperfusion injury is mediated in part by activation of the stress kinase JNK, but whether MIF modulates JNK in this setting is unknown. We examined the role of MIF in regulating JNK activation and cardiac injury during experimental ischemia/reperfusion in mouse hearts. Isolated perfused Mif-/- hearts had greater contractile dysfunction, necrosis, and JNK activation than WT hearts, with increased upstream MAPK kinase 4 phosphorylation, following ischemia/reperfusion. These effects were reversed if recombinant MIF was present during reperfusion, indicating that MIF deficiency during reperfusion exacerbated injury. Activated JNK acts in a proapoptotic manner by regulating BCL2-associated agonist of cell death (BAD) phosphorylation, and this effect was accentuated in Mif-/- hearts after ischemia/reperfusion. Similar detrimental effects of MIF deficiency were observed in vivo following coronary occlusion and reperfusion in Mif-/- mice. Importantly, excess JNK activation also was observed after hypoxia-reoxygenation in human fibroblasts homozygous for the MIF allele with the lowest level of promoter activity. These data indicate that endogenous MIF inhibits JNK pathway activation during reperfusion and protects the heart from injury. These findings have clinical implications for patients with the low-expression MIF allele.
Different modes of assisted ventilation in patients with acute respiratory failure
Authors: D. Chiumello, P. Pelosi, E. Calvi, L.M. Bigatello, L. Gattinoni
Journal: European Respiratory Journal (2002)

The aim of the present study was to verify that the patient/ventilator interaction is similar, regardless of the mode of assisted mechanical ventilation ( i.e. pressure- or volume-limited) used, if tidal volume ( V T ) and peak inspiratory flow (PIF) are matched. Therefore, the authors compared the effects of three different modes of assisted ventilation on the work of breathing (WOB) and gas exchange in patients with acute respiratory failure. For Protocol 1, in seven patients, the authors compared pressure support, assist pressure control and assist control (with square and decelerating wave inspiratory flow pattern) set to deliver the same V T and PIF. For Protocol 2, in another 10 patients, the authors compared pressure support and assist control with high (0.8 L·s −1 ) and low (0.6 L·s −1 ) PIFs set to deliver the same V T . In Protocol 1, there was no difference in WOB and gas exchange between the three modes of assisted ventilation tested. In Protocol 2, the decrease of PIFs during assist control significantly increased WOB. In conclusion, different modes of assisted ventilation similarly reduce work of breathing and provide adequate gas exchange at fixed tidal volume and peak inspiratory flow only. During assist control, tidal volume and peak inspiratory flow (set by the physician) are the main determinants of the patient/ventilator interaction.
PTU-083 Caudate lobe resection for colorectal liver metastases: a matched pair analysis
Authors: G Marangoni, A Hakeem, R K Prasad, G J Toogood, J P A Lodge
Journal: Gut (2012)

<h3>Introduction</h3> Tumours located in the caudate lobe can be challenging due to the anatomical relation of segment I with the inferior vena cava (IVC), the presence of multiple small caudate veins, variable bile ducts anatomy and difficult exposure during surgery. Some groups reported increased morbidity, smaller resection margins and inferior outcomes. Aim of the study was to compare the group of patients who underwent caudate lobe resection (CLR) with a group of patients without caudate lobe excision (NCLR). <h3>Methods</h3> Over a 16-year period, from November 1994 to November 2010, 1295 consecutive liver resections for colorectal liver metastases were performed at our Institution. The cohort of caudate resection patients were age (±1 year), sex and number of resected segments matched with an exact number of other hepatic resection patients that did not include the caudate lobe. Seventy-five patients had CLR. Six patients who had isolated CLR were excluded leaving 69 cases from analysis. <h3>Results</h3> ASA score, comorbidity, number of bilateral resections, steatosis and fibrosis did not differ among the cohorts (p=NS). Similarly the number of tumours, size of the largest tumour and resection margins (R0 vs R1) did not differ among the two groups (p=NS). Post-operative stay (13.5 vs 10.9 days), ICU admissions (16 vs 7), morbidity (sepsis, bile leak, cardio-vascular, respiratory; 26 vs 27), number of patients transfused (7 vs 5), hepatic failure (7 vs 6) and 60-days mortality (1 vs 2) were not significant (CLR vs NCLR, p=NS). Overall survival at 1, 3 and 5 years were 85%, 57% and 48% for CLR and 95%, 61% and 50% for NCLR respectively. Disease-free survival at 1, 3, and 5 years were 75%, 47% and 47% for CLR and 85%, 63% and 53% respectively. <h3>Conclusion</h3> Although caudate lobe involvement adds to the technical complexity of hepatic resection, it does not appear to carry increased morbidity and mortality when associated to major liver surgery. The rate of R0 resection and overall and disease-free survival does not differ between CLR and NCLR. <h3>Competing interests</h3> None declared.
The contribution of increased collagen synthesis to human glomerulosclerosis: a quantitative analysis of alpha 2IV collagen mRNA expression by competitive polymerase chain reaction.
Authors: E P Peten, L J Striker, M A Carome, S J Elliott, C W Yang, G E Striker
Journal: The Journal of Experimental Medicine (1992)

We previously reported that one of the main components of the sclerotic material in human glomerular diseases was type IV collagen. In this study we examined the contribution of increased synthesis to this process at the gene expression level. Sufficient material has not been available to study type IV collagen synthesis by normal or sclerotic glomeruli in humans. We took advantage of the availability of nephrectomy specimens from patients with renal carcinoma, and of the observation that approximately 50% of these patients develop varying degrees of glomerulosclerosis. We microdissected glomeruli from 10 patients and analyzed them using in situ reverse transcription coupled with polymerase chain reaction (PCR) analyses (in situ RT-PCR). alpha 2IV collagen mRNA, after reverse transcription into cDNA, was detected in all patients and appeared to be increased in those with glomerulosclerosis (n = 5). A competitive PCR assay was developed to quantitate this change. There was an average 3.7-fold increase in glomerular type IV collagen cDNA in patients with significant sclerosis. This change was not due to an increased number of glomerular cells. Thus, glomerulosclerosis in humans is associated with an elevation of glomerular type IV collagen gene expression, suggesting that increased synthesis of type IV collagen may represent one component of this process.