tbuckley/cabot-search huggingface dataset:
Methotrexate and Lung Disease in Rheumatoid Arthritis: A Meta‐Analysis of Randomized Controlled Trials
Authors: Richard Conway, Candice Low, Robert J. Coughlan, Martin J. O'Donnell, John J. Carey
Journal: Arthritis & Rheumatology (2013)

Objective Methotrexate has shown efficacy for the treatment of several diseases, especially rheumatoid arthritis (RA). Methotrexate has also been implicated as a causative agent in interstitial lung disease. Patients with RA may develop pulmonary manifestations of their disease and are at increased risk of respiratory infection. The aim of this study was to evaluate the relative risk (RR) of pulmonary disease among patients with RA treated with methotrexate. Methods We searched the PubMed and Cochrane databases (publication dates January 1, 1990 to February 1, 2013) for double‐blind, randomized, controlled trials of methotrexate versus placebo or active comparator agents in adults with RA. Studies with &lt;100 subjects or with a duration of &lt;24 weeks were excluded. Two investigators independently searched both databases, and all of the investigators reviewed the selected studies. We compared differences in the RR using the Mantel‐Haenszel random‐effects method. Results A total of 22 studies with 8,584 participants met the inclusion criteria. Heterogeneity across studies was not significant (I 2 = 3%), allowing combination of the trial results. Methotrexate was associated with an increased risk of all adverse respiratory events (RR 1.10, 95% confidence interval [95% CI] 1.02−1.19) and respiratory infection (RR 1.11, 95% CI 1.02−1.21). Patients treated with methotrexate were not at increased risk of death due to lung disease (RR 1.53, 95% CI 0.46−5.01) or noninfectious respiratory events (RR 1.02, 95% CI 0.65−1.60). A subgroup analysis of studies in which pneumonitis was described revealed an increased risk associated with methotrexate (RR 7.81, 95% CI 1.76−34.72). Conclusion Our study demonstrated a small but significant increase in the risk of lung disease in patients with RA treated with methotrexate compared with other disease‐modifying antirheumatic drugs and biologic agents.
Abstract 10805: Does the 12-lead ECG Have Limitations in Detecting Hypertrophic Cardiomyopathy in the Pre-Participation Screening of Athletes?
Authors: Ethan J Rowin, Evan Appelbaum, Thomas H Hauser, Caitlin Harrigan, C. Michael Gibson, John R Lesser, Tammy S Haas, James E Udelson, Warren J Manning, Barry J Maron, Martin S Maron
Journal: Circulation (2011)

Background. Pre-participation screening of athletes with 12-lead electrocardiograms (ECGs) has been recommended for detection of asymptomatic cardiovascular disease, particularly hypertrophic cardi...
ABC of oxygen: Oxygen transport---1. Basic principles
Authors: D F Treacher, R M Leach
Journal: BMJ (1998)

Mammalian life and the bioenergetic processes that maintain cellular integrity depend on a continuous supply of oxygen to sustain aerobic metabolism. Reduced oxygen delivery and failure of cellular use of oxygen occur in various circumstances and if not recognised result in organ dysfunction and death. Prevention, early identification, and correction of tissue hypoxia are essential skills. An understanding of the key steps in oxygen transport within the body is essential to avoid tissue hypoxia.



Red blood cells entering a capillary



Although oxygen is the substrate that cells use in the greatest quantity and on which aerobic metabolism and cell integrity depend, the tissues have no storage system for oxygen. They rely on a continuous supply at a rate that precisely matches changing metabolic requirements. If this supply fails, even for a few minutes, tissue hypoxaemia may develop resulting in anaerobic metabolism and production of lactate.

### Key steps in oxygen cascade



Oxygen transport from atmosphere to mitochondria. Values given in parenthesis are for a healthy 70 kg adult breathing air (FiO2 0.21) at standard barometric pressure



View this table:

Partial pressures of oxygen at sea level (101 kPa)



Oxygen transport from environmental air to the mitochondria of individual cells occurs as a series of steps. The heart, lungs, and circulation extract oxygen from the atmosphere and generate a flow of oxygenated blood to the tissues to maintain aerobic metabolism. The system must be energy efficient (avoiding unnecessary cardiorespiratory work), match oxygen distribution with metabolic demand, and allow efficient oxygen transport across the extravascular tissue matrix. At the tissue level, cells must extract oxygen from the extracellular environment and use it efficiently in cellular metabolic processes.

Arterial oxygen tension (PaO2 …
Antidepressant effects of light in seasonal affective disorder
Authors: Norman E Rosenthal, David A. Sack, Constance J. Carpenter, Barbara L. Parry, Wallace B. Mendelson, Thomas A. Wehr
Journal: American Journal of Psychiatry (1985)

The authors treated winter depression in 13 patients with typical seasonal affective disorder by extending the length of winter days with bright and dim light in the morning and evening in a balanced-order crossover study. Bright light had a marked antidepressant effect, whereas the dim light did not. This response could not be attributed to sleep deprivation. Subsequent pilot studies indicated that bright evening light alone is probably also effective. Several patients were able to maintain the antidepressant response throughout the winter months by continuing daily light treatments.
Identification of a mitochondrial defect gene signature reveals NUPR1 as a key regulator of liver cancer progression
Authors: Young‐Kyoung Lee, Byul A. Jee, So Mee Kwon, Young‐Sil Yoon, Wei Guang Xu, Hee‐Jung Wang, Xin Wei Wang, Snorri S. Thorgeirsson, Jae‐Seon Lee, Hyun Goo Woo, Gyesoon Yoon
Journal: Hepatology (2015)

Many cancer cells require more glycolytic adenosine triphosphate production due to a mitochondrial respiratory defect. However, the roles of mitochondrial defects in cancer development and progression remain unclear. To address the role of transcriptomic regulation by mitochondrial defects in liver cancer cells, we performed gene expression profiling for three different cell models of mitochondrial defects: cells with chemical respiratory inhibition (rotenone, thenoyltrifluoroacetone, antimycin A, and oligomycin), cells with mitochondrial DNA depletion (Rho0), and liver cancer cells harboring mitochondrial defects (SNU354 and SNU423). By comparing gene expression in the three models, we identified 10 common mitochondrial defect–related genes that may be responsible for retrograde signaling from cancer cell mitochondria to the intracellular transcriptome. The concomitant expression of the 10 common mitochondrial defect genes is significantly associated with poor prognostic outcomes in liver cancers, suggesting their functional and clinical relevance. Among the common mitochondrial defect genes, we found that nuclear protein 1 ( NUPR1 ) is one of the key transcription regulators. Knockdown of NUPR1 suppressed liver cancer cell invasion, which was mediated in a Ca 2+ signaling–dependent manner. In addition, by performing an NUPR1‐ centric network analysis and promoter binding assay, granulin was identified as a key downstream effector of NUPR1 . We also report association of the NUPR1 –granulin pathway with mitochondrial defect–derived glycolytic activation in human liver cancer. Conclusion : Mitochondrial respiratory defects and subsequent retrograde signaling, particularly the NUPR1 –granulin pathway, play pivotal roles in liver cancer progression. (H epatology 2015;62:1174‐1189)
Abstract 16451: Quinacrine as a Novel Anti-Restenotic and Anti-Thrombotic Drug for Coronary Artery Interventions
Authors: Cinzia Perrino, Giuseppe Gargiulo, Gabriele G Schiattarella, Gianluigi Pironti, Luigi Di Serafino, Laura Scudiero, Federica Serino, Federica Ilardi, Gianluca Petrillo, Plinio Cirillo, Giovanni Esposito
Journal: Circulation (2011)

Background Coronary drug eluting stents (DES) have significantly reduced the rate of in-stent restenosis, but have also increased the rate of vessel thrombosis and, in turn, the duration of dual an...
Is it useful CD4+CD103+/CD4+ ratio for the diagnosis of lung sarcoidosis?
Authors: Laimute Jurgauskiene, Edvardas Danila, Radvile Malickaite
Journal: European Respiratory Journal (2011)

The diagnosis of lung sarcoidosis relies in part on the observation of alveolar CD4+ cells and the demonstration of an increased CD4/CD8 ratio. This ratio has been proposed as a diagnostic tool for pulmonary sarcoidosis. But this anomaly is also found in other lung diseases too. The search for other pathognomonic criteria allowing the discrimination of sarcoidosis patients (pts.) from patients with CD4+ alveolar lymphocytosis has been disappointing.  We investigated CD103 molecules on the T lymphocytes subpopulations. The expression of these molecules was examined on BAL lymphocytes from sarcoid patients with different radiologycal stages (Ist. – 23 pts; II – 16 pts: III – 9 pts.) and Lefgren9s sindrome (25 pts) and patients with other lung disemination (17 pts.). For all patients, the expression of CD3, CD4, CD8 and CD103 was assessed by flow cytometry.  We found that CD4+/CD8+ ratio in I stage was 6,5±4,1; II st. – 4,5±2,3, III st. – 4,1±3,3, Lefgren9s sindrome – 8,6±4,9 and other lung disemination – 1,9±1,7. CD4+CD103+/CD4+ ratio in I st. – 0,2±0,1; 0,2±0,1; 0,2±0,1; 0,1±0,1 and 0,4±0,2 respectively. CD4+CD103+/CD4+ ratio differ significally (p  Our findings demonstrate that the combined use of CD4+/CD8+ and CD4+CD103+/CD4+ ratios provides a highly sensitive indicator of lung sarcoidosis in patients with other CD4+ BAL lymphocytosis.
Abstract 1764: Coapsys(R) Leads to Global Reversal of Left Ventricular Remodeling: Expanded TRACE Study Analysis
Authors: Sanjay Mittal, Yugal Mishra, Naresh Trehan
Journal: Circulation (2007)

Background: . We have previously reported as a part of the TRACE study that patients with LV dysfunction undergoing CABG and surgical implantation of Coapsys had significant reductions in LV size a...
Abstract 2197: The Multi-System Effect of Exercise Training During Prolonged Bed Rest Deconditioning: An Integrated Approach to Countermeasure Development for the Heart, Lungs, Muscle and Bones
Authors: Jeffrey Hastings, Eric Pacini, Felix Krainski, Shigeki Shibata, Manish Jain, Peter Snell, Qi Fu, Michael D Palmer, Daniel Creson, Benjamin D Levine
Journal: Circulation (2008)

We propose to prevent the cardiac atrophy and orthostatic intolerance associated with prolonged bed rest using rowing ergometry/resistance training with aggressive volume loading on the day of testing. We hypothesize that prevention of cardiac atrophy will forestall cardiovascular deconditioning, leading to preserved exercise capacity and orthostatic tolerance. Twenty-four healthy subjects, ages 20 –55, were enrolled with 8 randomized to training (EX), 8 with training and volume loading (VOL), and 8 as sedentary (SED) controls. Testing included maximal upright exercise, orthostatic tolerance via graded lower body negative pressure (LBNP), cardiac MRI, as well as invasive cardiac pressure-volume measurements, performed at baseline and at the end of 5 weeks of 6° head down bedrest. Upright exercise capacity was preserved with training as measured by peak workrate and VO2max (EX/VOL: pre 195±46W, 34±7 ml/kg/min; post 202±42W, 33±4 ml/kg/min) but deteriorated in SED group (pre 171±55W, 34±8 ml/kg/min; post 145±51W, 27±7 ml/kg/min). MRI derived mass (% change: +6.3±9.9% EX/VOL vs. −5.5±3.7% SED) was increased by training. Exercise training appears to preserve LV chamber compliance (stiffness constants: EX/VOL: pre= 0.035±0.021, post = 0.036±0.029; SED: pre= 0.020±0.011, post = 0.028±0.007). Training also preserves hemodynamic variables measured at −40mmHg of LBNP, including stroke volume (EX: pre 44±12; post 38±9 ml, VOL: pre 49±30; post 45±29 ml, SED: pre 35±5; post 24±8 ml ). These preliminary data support our hypothesis that an optimized training program consisting of dynamic and resistance exercise can prevent part of the multisystem atrophy and orthostatic intolerance associated with prolonged bed rest. This defines a specific countermeasure that is practical, safe, and effective against the cardiovascular, muscle and bone deconditioning associated with prolonged bed rest. This information is relevant not only for astronauts exposed to long duration spaceflight, but also for patients with chronic reductions in physical activity, and those with disease processes that alter cardiac stiffness such as obesity, hypertension, heart failure or ischemic heart disease, plus normal aging and osteoporosis. This research has received full or partial funding support from the American Heart Association, AHA South Central Affiliate (Arkansas, New Mexico, Oklahoma &amp; Texas).
THE CONCOMITANCE OF ORGANIC AND PSYCHOLOGIC CHANGES DURING MARKED IMPROVEMENT IN SCHIZOPHRENIA
Authors: Milton H. Erickson
Journal: American Journal of Psychiatry (1934)

Detailed psychiatric, psychologic and physiologic studies were made for a period of seven months on a patient suffering from schizophrenia, catatonic reaction type. Three distinct psychiatric states—namely, stupor, recovery from the stupor and a condition of apparent recovery from the psychosis— were found, for each of which a physiological cross-sectional study was made. During the stuporous state he was under-weight, had diminished oxygen consumption, reduced body temperature, polyuria and delayed colonic emptying time. Other physiological findings were essentially normal. During the second period he had recovered from the stupor, had gained weight, manifested a slight, equivocal decrease in his oxygen consumption rate, a slight increase in body temperature, mild secondary anemia, a questionable low blood volume and low venous and arterial oxygen content. Other findings were within normal ranges. During the third period the patient appeared to have reached the level of his pre-institutional mental state, had gained weight and manifested a normal oxygen consumption rate, with normal body temperature. Except for a marked polyuria and low venous oxygen content, the physical data showed no apparently significant deviation from the normal. There is evidence suggestive of a pituitary deficiency manifested at about puberty, according to the history, and also during the first and third periods of study. However, the fluctuations noted could likewise be attributed to an abnormal functioning of the hypothalamus. In brief, coincidental with the changes in the psychiatric and psychological spheres, there have been corresponding or opposite fluctuations and variations in the organic sphere. Also, in some instances, an apparent independence has been indicated by physiologic constancy. Accordingly, when more studies of this nature have been made, an answer to the question of functional interdependence may be achieved.
An hour that might have made history: Before transfusion became established procedure
Authors: F. Boulton
Journal: BMJ (1999)

Between 11 00 am and 12 00 noon on 20 May 1910, Thomas Addis transfused “about 300cc of freshly drawn human phosphated blood” to a patient with haemophilia whose plasma clotting time was thereby shortened from 245 to 24 minutes (normal, 13 minutes). It was 30 minutes two days later, 32 at four days, 55 at eight days, and 200 at 25 days.

Throughout 1910 Addis was Carnegie research fellow at the laboratories of the Royal College of Physicians of Edinburgh, close to the Royal Infirmary at No 2 Forrest Road. The transfusion was his only recorded foray in vivo; he was otherwise investigating the haemophilic abnormality in vitro. His methods with oxalated venous blood plasma …
Autophagy is induced upon platelet activation and is essential for hemostasis and thrombosis
Authors: Madhu M. Ouseph, Yunjie Huang, Meenakshi Banerjee, Smita Joshi, Laura MacDonald, Yu Zhong, Huijuan Liu, Xianting Li, Binggang Xiang, Guoying Zhang, Masaaki Komatsu, Zhenyu Yue, Zhenyu Li, Brian Storrie, Sidney W. Whiteheart, Qing Jun Wang
Journal: Blood (2015)
Evaluation of cancer risk related to atopic dermatitis and use of topical calcineurin inhibitors
Authors: P. Tennis, J.M. Gelfand, K.J. Rothman
Journal: British Journal of Dermatology (2011)

Cases of lymphoma or cutaneous cancer have been observed following use of topical calcineurin inhibitors (TCIs), but it is unclear whether TCI use increases cancer risk. We used published literature to assess the extent to which atopic dermatitis (AD) or TCI use is associated with lymphoma, melanoma, basal cell carcinoma and squamous cell carcinoma. We searched the literature and summarized the results of all studies that provided data on the absolute or relative frequency of any malignancy among patients with AD or eczema or among patients using TCIs. The relative risk for all lymphoma in broad populations of AD or eczema ranged from 0·7 to 1·8. Available data on lymphoma following TCI use were inconsistent and insufficient to draw a conclusion about the causal role of TCIs. We found no evidence indicating that melanoma or nonmelanoma skin cancer is associated with TCI use. A bias analysis showed that cutaneous T-cell lymphomas initially misdiagnosed and treated as AD would lead to overestimation of the association between TCI use and lymphoma. However, there are only sparse data on specific malignancies among TCI-treated patients. The short duration of typical TCI exposure hinders conclusions about longer exposure. There is insufficient evidence in the epidemiological literature to infer whether TCIs do or do not cause malignancy.
Abstract 6146: Atherosclerotic-Like Processes in Human Aortic Valve Disease: Role of Tissue Factor and Other Components of Atherosclerosis
Authors: Joke Breyne, Sylvestre Marechaux, Francis Juthier, Christophe Zawadzki, Delphine Corseaux, Andre Vincentelli, Thierry Le Tourneau, Brigitte Jude
Journal: Circulation (2008)
Epidemiology of congenital pigmented naevi:.
Authors: EDUARDO E. CASTILLA, MARIA GRACA DUTRA, IEDA M. ORIOLI-PARREIRAS
Journal: British Journal of Dermatology (1981)

Genetic and environmental risks factors were investigated in a sample of 989 non-malformed newborn infants with skin pigmented naevi (PN), and in 989 non-malformed non-PN, control babies. The samples were obtained from a population of 531,831 livebirths, from fifty-nine South-American maternity hospitals. No significant differences were observed between the PN and control groups for the following risk factors: sex, twinning, parental consanguinity, socioeconomic level, parental ages, birth order, fetal presentation, type of delivery, postnatal mortality, and first trimester of pregnancy histories for maternal chronic illnesses or immunizations, radiation exposure, drug intake, and vaginal bleeding. PN infants were associated with high frequencies of Black racial ancestry, positive prenatal history for maternal acute illnesses, and high mean values for length of gestation and birth weight. The observed association of PN with maternal acute illnesses could be a spurious one, due to partial dependence upon Black racial ancestry, and to maternal memory bias. The analysis of the intrauterine growth curves showed that PN infants have a low prematurity rate, and a high mean by the control newborn group. This observation suggest that congenital PN appear in the latest stages of intrauterine development. No evidence was obtained to allow us to consider congenital PN as true developmental anomalies.
Abstract 15444: Vitamin D Signaling Pathway Plays an Important Role in the Development of Heart Failure After Myocardial Infarction (MI) by Modulating Apoptosis
Authors: Soochan Bae, Hyeon Yu, Sylvia S Singh, Ji Y Lee, Peter M Kang
Journal: Circulation (2011)

Vitamin D deficiency has been associated with increased incidence of heart failure, and activation of vitamin D signaling has been shown to have cardioprotective effects. In this study, we examined...
Atrophy of Myocardium and Its Myocytes by Left Ventricular Assist Device
Authors: Louis A. Soloff
Journal: Circulation (1999)

In a recent interesting article, 1 Zhang and Hintze stated that amlodipine but not nifedipine released nitric oxide from canine coronary microvessels and classified this as an unexpected mechanism of action.However, it should be noted that several years ago, the same phenomenon, ie, direct release of NO, was observed with nitrendipine in small porcine coronary arteries, porcine arteria basilaris, and porcine arteria caudalis. 2Similarly, the vasodilating action of nitrendipine, nifedipine, nisoldipine, and nimodipine in guinea pig mesenteric vascular beds was found to be sensitive to L-N G -nitroarginine treatment. 3 The latter was more pronounced in smaller arterioles (diameter Ͻ350 m).Regarding the mechanism of action underlying the release of NO, it was shown recently by use of the fura-2 technique that the calcium antagonist nitrendipine enhances the intracellular calcium concentration in suspensions of cultured endothelial cells. 4 This effect was insensitive to thapsigargin but was sensitive to extracellular depletion of calcium, indicating that the observed increase in intracellular calcium concentration was mainly due to an influx of calcium rather than a calcium release from intracellular stores.The elevation of intracellular calcium by nitrendipine could be completely blocked by application of gadolinium, a trivalent lanthanide known to inhibit shear stress-activated cation-selective channels on endothelial cells.In addition, the authors showed that the increase in intracellular [Ca 2ϩ ] by shear stress was further enhanced in the presence of nitrendipine. 4 In summary, the release of NO from vascular endothelium is not unique to amlodipine but seems to be a group phenomenon of 1,4-dihydropyridines.The NO release may be more or less prominent when various substances in various vessel types are compared.As shown, the NO dependence of vasodilation by 1,4-dihydropyridines may also be influenced by the position of the vessels within the vascular tree. 3 In addition, this NOreleasing action is not restricted to vascular endothelium but can also be found in platelets, as shown for nifedipine, and contributes to its antiaggregatory effects.
Association of Germline p53 Mutation With MLL Segmental Jumping Translocation in Treatment-Related Leukemia
Authors: Carolyn A. Felix, Maureen D. Megonigal, David S. Chervinsky, Debra G.B. Leonard, Nao Tsuchida, Surabhi Kakati, Anne Marie W. Block, John Fisher, Mauro Grossi, Kevin I. Salhany, Sheila N. Jani-Sait, Peter D. Aplan
Journal: Blood (1998)