tbuckley/cabot-search huggingface dataset:
Effects of cannabis on lung function: a population-based cohort study
Authors: R. J. Hancox, R. Poulton, M. Ely, D. Welch, D. R. Taylor, C. R. McLachlan, J. M. Greene, T. E. Moffitt, A. Caspi, M. R. Sears
Journal: European Respiratory Journal (2009)

The effects of cannabis on lung function remain unclear and may be different from those of tobacco. We compared the associations between use of these substances and lung function in a population-based cohort (n = 1,037). Cannabis and tobacco use were reported at ages 18, 21, 26 and 32 yrs. Spirometry, plethysmography and carbon monoxide transfer factor were measured at 32 yrs. Associations between lung function and exposure to each substance were adjusted for exposure to the other substance. Cumulative cannabis use was associated with higher forced vital capacity, total lung capacity, functional residual capacity and residual volume. Cannabis was also associated with higher airway resistance but not with forced expiratory volume in 1 s, forced expiratory ratio or transfer factor. These findings were similar among those who did not smoke tobacco. In contrast, tobacco use was associated with lower forced expiratory volume in 1 s, lower forced expiratory ratio, lower transfer factor and higher static lung volumes, but not with airway resistance. Cannabis appears to have different effects on lung function from those of tobacco. Cannabis use was associated with higher lung volumes, suggesting hyperinflation and increased large-airways resistance, but there was little evidence for airflow obstruction or impairment of gas transfer.
Tax fraud GP is struck off for persistent dishonesty
Authors: Clare Dyer
Journal: BMJ (2015)

A general practitioner who was sentenced to 18 months in prison after admitting to defrauding the UK tax authorities of £185 000 (€255 000; $285 000) has been struck off by the Medical Practitioners Tribunal Service.

The tribunal panel concluded that Michael Summer’s actions had “damaged the reputation of the medical profession and degraded the public’s trust in it.”

Summer had previously worked as a locum GP but began earning more after 2009 when he set up as a GP in private practice, carrying out medical examinations in personal injury cases and for the armed forces. From 2008 to 2012 he increasingly under-declared his income, culminating in the tax …
Allogeneic Hematopoietic Cell Transplantation for Fanconi Anemia in Patients With Pretransplantation Cytogenetic Abnormalities, Myelodysplastic Syndrome, or Acute Leukemia
Authors: Mouhab Ayas, Wael Saber, Stella M. Davies, Richard E. Harris, Gregory A. Hale, Gerard Socie, Jennifer LeRademacher, Monica Thakar, H. Joachim J. Deeg, Amal Al-Seraihy, Minoo Battiwalla, Bruce M. Camitta, Richard Olsson, Rajinder S. Bajwa, Carmem M. Bonfim, Ricardo Pasquini, Margaret L. MacMillan, Biju George, Edward A. Copelan, Baldeep Wirk, Abdullah Al Jefri, Anders L. Fasth, Eva C. Guinan, Biljana N. Horn, Victor A. Lewis, Shimon Slavin, Polina Stepensky, Marc Bierings, Robert Peter Gale
Journal: Journal of Clinical Oncology (2013)

Purpose Allogeneic hematopoietic cell transplantation (HCT) can cure bone marrow failure in patients with Fanconi anemia (FA). Data on outcomes in patients with pretransplantation cytogenetic abnormalities, myelodysplastic syndrome (MDS), or acute leukemia have not been separately analyzed. Patients and Methods We analyzed data on 113 patients with FA with cytogenetic abnormalities (n = 54), MDS (n = 45), or acute leukemia (n = 14) who were reported to the Center for International Blood and Marrow Transplant Research from 1985 to 2007. Results Neutrophil recovery occurred in 78% and 85% of patients at days 28 and 100, respectively. Day 100 cumulative incidences of acute graft-versus-host disease grades B to D and C to D were 26% (95% CI, 19% to 35%) and 12% (95% CI, 7% to 19%), respectively. Survival probabilities at 1, 3, and 5 years were 64% (95% CI, 55% to 73%), 58% (95% CI, 48% to 67%), and 55% (95% CI, 45% to 64%), respectively. In univariate analysis, younger age was associated with superior 5-year survival (≤ v &gt; 14 years: 69% [95% CI, 57% to 80%] v 39% [95% CI, 26% to 53%], respectively; P = .001). In transplantations from HLA-matched related donors (n = 82), younger patients (≤ v &gt; 14 years: 78% [95% CI, 64% to 90%] v 34% [95% CI, 20% to 50%], respectively; P &lt; .001) and patients with cytogenetic abnormalities only versus MDS/acute leukemia (67% [95% CI, 52% to 81%] v 43% [95% CI, 27% to 59%], respectively; P = .03) had superior 5-year survival. Conclusion Our analysis indicates that long-term survival for patients with FA with cytogenetic abnormalities, MDS, or acute leukemia is achievable. Younger patients and recipients of HLA-matched related donor transplantations who have cytogenetic abnormalities only have the best survival.
Cyclophosphamide, Epirubicin, and Fluorouracil Versus Dose-Dense Epirubicin and Cyclophosphamide Followed by Paclitaxel Versus Doxorubicin and Cyclophosphamide Followed by Paclitaxel in Node-Positive or High-Risk Node-Negative Breast Cancer
Authors: Margot Burnell, Mark N. Levine, Judith-Anne W. Chapman, Vivien Bramwell, Karen Gelmon, Barbara Walley, Ted Vandenberg, Haji Chalchal, Kathy S. Albain, Edith A. Perez, Hope Rugo, Kathleen Pritchard, Patti O'Brien, Lois E. Shepherd
Journal: Journal of Clinical Oncology (2009)

PURPOSE Cyclophosphamide, epirubicin, and fluorouracil (CEF) and doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) are commonly used adjuvant regimens in women with early breast cancer. In a previous trial in women with locally advanced breast cancer, 3 months of high-dose epirubicin and cyclophosphamide (EC) administered every 2 weeks (dose-dense) was equivalent to 6 months of CEF. We hypothesized that 3 months of paclitaxel after dose-dense EC (EC/T) would be superior to CEF or AC/T. METHODS After lumpectomy or mastectomy, women 60 years of age or younger with axillary node-positive or high-risk node-negative breast cancer were randomly assigned to receive CEF, EC/T, or AC/T for 6 months. This article reports the interim analysis for recurrence-free survival (RFS), which was planned after 227 recurrences. Results A total of 2,104 patients were enrolled. The median follow-up is 30.4 months. Hazard ratios for recurrence are as follows: AC/T versus CEF, 1.49 (95% CI, 1.12 to 1.99), P = .005; AC/T versus EC/T, 1.68 (95% CI, 1.25 to 2.27), P = .0006; and EC/T versus CEF, 0.89 (95% CI, 0.64 to 1.22), P = .46. Three-year RFS rates for CEF, EC/T, and AC/T are 90.1%, 89.5%, and 85.0%, respectively. There was more febrile neutropenia with CEF (22.3%) and EC/T (16.4%) compared with AC/T (4.8%), but more neuropathy with the last two regimens. CONCLUSION Three-weekly AC/T is significantly inferior to CEF or EC/T in terms of RFS. It is too early to detect any difference between CEF and dose-dense EC/T.
DNA methylation and body-mass index: a genome-wide analysis
Authors: Katherine J Dick, Christopher P Nelson, Loukia Tsaprouni, Johanna K Sandling, Dylan Aïssi, Simone Wahl, Eshwar Meduri, Pierre-Emmanuel Morange, France Gagnon, Harald Grallert, Melanie Waldenberger, Annette Peters, Jeanette Erdmann, Christian Hengstenberg, Francois Cambien, Alison H Goodall, Willem H Ouwehand, Heribert Schunkert, John R Thompson, Tim D Spector, Christian Gieger, David-Alexandre Trégouët, Panos Deloukas, Nilesh J Samani
Journal: The Lancet (2014)
Doxycycline-induced expression of sense and inverted-repeat constructs modulates phosphogluconate mutase (Pgm) gene expression in adult Drosophila melanogaster
Authors: Michael J Allikian, Denise Deckert-Cruz, Michael R Rose, Gary N Landis, John Tower
Journal: Genome biology (2002)

A tetracycline-regulated (conditional) system for RNA interference (RNAi) would have many practical applications. Such a strategy was developed using RNAi of the gene for phosphogluconate mutase (Pgm). Pgm is a candidate lifespan regulator: PgmS allele frequency is increased by selection for increased lifespan, whereas PgmM and PgmF allele frequencies are decreased. The Pgm alleles were cloned and sequenced and were found to differ by amino-acid substitutions consistent with the relative electrophoretic mobilities of the proteins. The 'tet-on' doxycycline-regulated promoter system was used to overexpress PgmS in a wild-type (PgmM) background. Enzyme activity increases of two- to five-fold were observed in five independent transgenic lines. Tet-on was also used to drive expression of an inverted-repeat fragment of Pgm coding region. The inverted-repeat transcript was expected to form a dsRNA hairpin, induce RNAi, and thereby reduce endogenous Pgm gene expression at the RNA level. Endogenous Pgm RNA levels in adult flies were found to be reduced or eliminated by doxycycline treatment in five independent inverted-repeat transgenic lines. Our results show that doxycycline-regulated expression of inverted-repeat constructs can cause a conditional reduction in specific gene expression. The effect of sense and inverted-repeat construct expression on lifespan was assayed in multiple transgenic lines. Under the conditions tested, altered Pgm gene expression had no detectable effect on adult Drosophila lifespan. A system for conditional RNAi in Drosophila adults shows promise for assay of gene functions during aging. Our results indicate that Pgm does not have a simple strong effect on longevity.
Determination of Krebs cycle metabolic carbon exchange in vivo and its use to estimate the individual contributions of gluconeogenesis and glycogenolysis to overall glucose output in man.
Authors: A Consoli, F Kennedy, J Miles, J Gerich
Journal: Journal of Clinical Investigation (1987)

Current isotopic approaches underestimate gluconeogenesis in vivo because of Krebs cycle carbon exchange and the inability to measure intramitochondrial precursor specific activity. We therefore applied a new isotopic approach that theoretically overcomes these limitations and permits quantification of Krebs cycle carbon exchange and the individual contributions of gluconeogenesis and glycogenolysis to overall glucose output. [6-3H]Glucose was infused to measure overall glucose output; [2-14C]acetate was infused to trace phosphoenolpyruvate gluconeogenesis and to calculate Krebs cycle carbon exchange as proposed by Katz. Plasma [14C]3-OH-butyrate specific activity was used to estimate intramitochondrial acetyl coenzyme A (CoA) specific activity, and finally the ratio between plasma glucose 14C-specific activity and the calculated intracellular phosphoenolpyruvate 14C-specific activity was used to determine the relative contributions of gluconeogenesis and glycogenolysis to overall glucose output. Using this approach, acetyl CoA was found to enter the Krebs cycle at twice (postabsorptive subjects) and three times (2 1/2-d fasted subjects) the rate of pyruvate, respectively. Gluconeogenesis in postabsorptive subjects (3.36 +/- 0.20 mumol/kg per min) accounted for 28 +/- 2% of overall glucose output and increased twofold in subjects fasted for 2 1/2-d (P less than 0.01), accounting for greater than 97% of overall glucose output. Glycogenolysis in postabsorptive subjects averaged 8.96 +/- 0.40 mumol/kg per min and decreased to 0.34 +/- 0.08 mumol/kg per min (P less than 0.01) after a 2 1/2-d fast. Since these results agree well with previously reported values for gluconeogenesis and glycogenolysis based on determinations of splanchnic substrate balance and glycogen content of serial liver biopsies, we conclude that the isotopic approach applied herein provides an accurate, noninvasive measurement of gluconeogenesis and glycogenolysis in vivo.
Echocardiographic Evaluation of Pericardial Disease
Authors: P. Anthony Chandraratna
Journal: JAMA (1983)

VARIOUS forms of pericardial disease are commonly encountered in clinical practice. Echocardiography is an effective noninvasive method of assessing many different cardiac conditions; this article explores the uses and limitations of echocardiography in evaluating pericardial disease, with a special emphasis on two-dimensional echocardiography. <h3>Pericardial Effusion</h3> One of the first applications of echocardiography was its use in diagnosing pericardial effusion.<sup>1</sup>The appearance of an echo-free space posterior to the heart, with disappearance or marked reduction of the space at the junction of the left ventricle and left atrium, and absence of motion of the pericardium are the echocardiographic hallmarks of pericardial effusion. The volume of pericardial fluid can be roughly quantitated using M-mode echocardiography. A small, posterior echo-free space denotes a small pericardial effusion, and as the amount of pericardial fluid increases, the posterior space becomes larger. With a large pericardial effusion, a large posterior as well as an anterior
Validation of a field test to determine the maximal aerobic power in triathletes and endurance cyclists
Authors: C González-Haro, P A Galilea, F Drobnic, J F Escanero
Journal: British Journal of Sports Medicine (2006)

Objective: To validate a field test to assess the maximal and submaximal exercise aerobic adaptation under specific conditions, for endurance modality cyclists and triathletes. Methods: 30 male and 4 female endurance modality cyclists and triathletes, with heterogeneous performance levels, performed three incremental tests: one in the laboratory and two in the field. Assessment of the validity of the field protocol was carried out by the Student’s t test, intraclass correlation coefficient (ICC) and coefficient of variation (CV) of the maximal variables (maximal aerobic speed (MAS), maximal aerobic power (MAP), maximal heart rate (HR max ), maximal blood lactate concentration ([La − ] max ) and maximal oxygen uptake (VO 2max )) and submaximal variables (heart rate, HR) measured in each one of the tests. The errors in measurement were calculated. The repeatability of the field tests was assessed by means of the test–retest of the two field tests, and the validity by means of the test–retest of the laboratory test with respect to the mean of the two field tests. Results: No significant differences were found between the two field tests for any of the variables studied, but differences did exist for some variables between the laboratory tests with respect to the field tests (MAP, [La − ] max , humidity (H), barometric pressure (Pb) and some characteristics of the protocols). The ICC of all the variables was high and the CV for the MAP was small. Furthermore, the measurement errors were small and therefore, assumable. Conclusions: The incremental protocol of the proposed field test turned out to be valid to assess the maximal and submaximal aerobic adaptation.
Integrin-Associated Protein Binding Domain of Thrombospondin-1 Enhances Insulin-Like Growth Factor-I Receptor Signaling in Vascular Smooth Muscle Cells
Authors: Laura A. Maile, David R. Clemmons
Journal: Circulation Research (2003)

Insulin-like growth factor-I (IGF-I) stimulates vascular smooth muscle cell (SMC) proliferation and migration. The response of smooth muscle cells to IGF-I is determined not only by activation of the IGF-I receptor but also by at least three other transmembrane proteins, alphaVbeta3, integrin-associated protein (IAP), and SHPS-1. This regulation seems to be attributable to their ability to regulate the transfer of SHP-2 phosphatase, a key component of IGF-I signaling. Ligand occupancy of SHPS-1 with IAP is required for the recruitment and transfer of SHP-2 and subsequent signaling in response to IGF-I. The extracellular matrix protein thrombospondin-1 stimulates an increase in the cell proliferation response to IGF-I. Because thrombospondin-1 is a ligand for IAP, we wished to determine whether the enhancing effect of thrombospondin-1 was mediated through IAP binding. To examine the effect of thrombospondin-1 binding to IAP, we used a peptide termed 4N1K derived from the IAP binding site of thrombospondin-1. Preincubation with 4N1K increased IGF-I-stimulated mitogen-activated protein kinase activation and DNA synthesis. This enhancement seemed to be attributable to its ability to increase the duration of IGF-I-stimulated receptor and insulin receptor substrate-1 (IRS-1) phosphorylation. Preincubation with 4N1K delayed IGF-I stimulation of SHPS-1 phosphorylation (attributable to an alteration in IAP-SHPS-1 interaction), resulting in a delay in SHP-2 recruitment. This delay in SHP-2 transfer seems to account for the increase in the duration of IGF-I receptor phosphorylation and for enhanced downstream signaling. These observations support the conclusion that thrombospondin-1 and IGF-I seem to function coordinately in stimulating smooth muscle proliferation via the thrombospondin-1 interaction with IAP.
Role of vagosympathetic fibers in the control of adrenocorticotropic hormone, vasopressin, and renin responses to hemorrhage in fetal sheep.
Authors: C E Wood, H G Chen, M E Bell
Journal: Circulation Research (1989)

Hemorrhage stimulates endocrine and cardiovascular reflex responses that are appropriate for returning blood volume and pressure to prehemorrhage levels. Fetal sheep respond to hemorrhage with increases in plasma adrenocorticotropic hormone (ACTH), cortisol, and vasopressin concentrations and plasma renin activity, but little is known about the afferent limb of the reflex(es) controlling these responses. Fetal sheep between 128 and 133 days' gestation were chronically prepared with vascular catheters. Five fetal sheep were subjected to bilateral section of the cervical vagosympathetic trunks; six fetal sheep were not vagotomized. Four to six days after surgery, the fetuses were subjected to withdrawal of 10 ml of blood every 10 minutes for 2 hours (130 ml total). Vagotomized fetal sheep responded to the hemorrhage with a greater decrease in central venous pressure than the intact fetuses and a slower restitution of fluid to the vascular space (estimated to be 17% of the hemorrhage volume in 2 hours) than the intact fetuses (estimated to be 28% of the hemorrhage volume in 2 hours). Both groups of fetuses, however, responded to the hemorrhage with increases in fetal plasma ACTH, cortisol, and vasopressin concentrations and plasma renin activity that were not significantly different. A posteriori analysis of the data by correlation analysis revealed that the fetal ACTH, vasopressin, and renin responses to the hemorrhage were more highly correlated to the changes in fetal arterial pH than to changes in fetal mean arterial pressure or central venous pressure. The results suggest that the ACTH, vasopressin, and renin responses to hemorrhage in the fetus be mediated by chemoreceptors, not by cardiovascular mechanoreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Sudden Cardiac Death After Myocardial Infarction in Type 2 Diabetic Patients With No Residual Myocardial Ischemia
Authors: Chun-Yip Yeung, Karen Siu-Ling Lam, Sheung-Wai Li, Kwok-Fai Lam, Hung-Fat Tse, Chung-Wah Siu
Journal: Diabetes Care (2012)

Diabetes mellitus (DM) is a well-established risk factor for coronary artery disease. Nonetheless, it remains unclear whether DM contributes to sudden cardiac death in patients who survive myocardial infarction (MI). The objective of this study was to compare the incidence of sudden cardiac death post-MI in diabetic and nondiabetic patients with no residual myocardial ischemia.A total of 610 consecutive post-MI patients referred to a cardiac rehabilitation program with negative exercise stress test were studied.Of these, 236 patients had DM at baseline. Over a mean follow-up of 5 years, 67 patients with DM (28.4%) and 76 of 374 patients without DM (20.2%) had died with a hazard ratio (HR) of 1.74 (95% CI: 1.28-2.56; P < 0.001). Patients with DM also had a higher incidence of cardiac death (1.84 [1.16-3.21]; P = 0.01), principally due to a higher incidence of sudden cardiac death (2.14 [1.22-4.23]; P < 0.001). Multiple Cox regression analysis revealed that only DM (adjusted HR: 1.9 [95% CI: 1.04-3.40]; P = 0.04), left ventricular ejection fraction (LVEF) ≤30% (3.6 [1.46-8.75]; P < 0.01), and New York Heart Association functional class >II (4.2 [1.87-9.45]; P < 0.01) were independent predictors for sudden cardiac death. Among patients with DM, the 5-year sudden cardiac death rate did not differ significantly among those with LVEF ≤30%, LVEF 31-50%, or LVEF >50% (8.8 vs. 7.8 vs. 6.8%, respectively; P = 0.83).Post-MI patients with DM, even in the absence of residual myocardial ischemia clinically, were at higher risk of sudden cardiac death than their non-DM counterparts.
Circulating Permeability Factors in the Nephrotic Syndrome
Authors: Richard J. Glassock
Journal: Journal of the American Society of Nephrology (2003)

The identification and characterization of circulating factors involved in the development of abnormal glomerular permeability to plasma proteins in the nephrotic syndrome has long been one of the holy grails of nephrology. Originally proposed by Shaloub in 1974 ([1][1]), such factors have often
Fitness Costs of Minimal Sequence Alterations Causing Protein Instability and Toxicity
Authors: Katarzyna Tomala, Elzbieta Pogoda, Agata Jakubowska, Ryszard Korona
Journal: Molecular Biology and Evolution (2013)

Destabilization of a protein impairs its metabolic efficiency. It is less clear how often destabilization also results in a gain of toxicity. We derived collections of temperature-sensitive, and thus structurally unstable, mutants of the yeast ADE2 and LYS2 genes by introducing single or very few amino acids substitutions. Overexpression of these mutant proteins led to a common, although unequal, fitness decrease. Interestingly, although the mutant proteins were functionally redundant, higher expression levels were associated with higher fitness. This result suggests that growth was hampered not by the accumulation of damaged chains but by the activities needed to remove them or by the damage caused before they were removed. Our results support the idea that any protein can become toxic when destabilized by a point mutation.
Panhypopituitarism Secondary to Hypothalamic Involvement in a Woman With Diffuse Large B-Cell Lymphoma
Authors: Theresa W. Chan, Paul Hoskins
Journal: Journal of Clinical Oncology (2010)

A 50-year-old woman presented with night sweats and weight loss.Computed tomography (CT) revealed bulky adenopathy involving the mesentery (16 cm), retroperitoneum, external iliac nodes, and mediastinum.Core biopsy of the mesenteric mass disclosed diffuse large B-cell lymphoma.Bone marrow was not involved at presentation; thus, she had stage IIIB disease.She received cyclophosphamide, doxorubicin,vincristine,prednisone,andrituximab(CHOP-R)chemotherapy, and interval CT scans showed positive response.She completed six cycles of chemotherapy without incident but presented 3 weeks after the final cycle with altered mental status.Head CT (Fig 1) revealed a 1.8-cm suprasellar mass associated with surrounding edema but no midline shift.Magnetic resonance imaging (MRI; Figs 2 and3) showed a 2.0 ϫ 1.8 cm suprasellar mass arising from the floor of the third ventricle, abutting the optic chiasm anteriorly, appearing hypothalamic in origin.The infundibulum and pituitary were within normal limits.The patient was started on dexamethasone and transferred to a tertiary care center a week later.At that time, the patient displayed personality changes but ate and drank ad libitum.
Chemotherapy with bevacizumab, irinotecan, 5-fluorouracil and leucovorin (IFL) associated with a large, embolizing thrombus in the thoracic aorta
Authors: S. Yoon, D. Schmassmann-Suhijar, M. Zuber, P. Konietzny, A. Schmassmann
Journal: Annals of Oncology (2006)