tbuckley/cabot-search huggingface dataset:
Therapeutic Hypothermia after Out-of-Hospital Cardiac Arrest in Children
Authors: Frank W. Moler, Faye S. Silverstein, Richard Holubkov, Beth S. Slomine, James R. Christensen, Vinay M. Nadkarni, Kathleen L. Meert, Amy E. Clark, Brittan Browning, Victoria L. Pemberton, Kent Page, Seetha Shankaran, Jamie S. Hutchison, Christopher J.L. Newth, Kimberly S. Bennett, John T. Berger, Alexis Topjian, Jose A. Pineda, Joshua D. Koch, Charles L. Schleien, Heidi J. Dalton, George Ofori-Amanfo, Denise M. Goodman, Ericka L. Fink, Patrick McQuillen, Jerry J. Zimmerman, Neal J. Thomas, Elise W. van der Jagt, Melissa B. Porter, Michael T. Meyer, Rick Harrison, Nga Pham, Adam J. Schwarz, Jeffrey E. Nowak, Jeffrey Alten, Derek S. Wheeler, Utpal S. Bhalala, Karen Lidsky, Eric Lloyd, Mudit Mathur, Samir Shah, Theodore Wu, Andreas A. Theodorou, Ronald C. Sanders, J. Michael Dean
Journal: New England Journal of Medicine (2015)

Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited.We conducted this trial of two targeted temperature interventions at 38 children's hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a Vineland Adaptive Behavior Scales, second edition (VABS-II), score of 70 or higher (on a scale from 20 to 160, with higher scores indicating better function), was evaluated among patients with a VABS-II score of at least 70 before cardiac arrest.A total of 295 patients underwent randomization. Among the 260 patients with data that could be evaluated and who had a VABS-II score of at least 70 before cardiac arrest, there was no significant difference in the primary outcome between the hypothermia group and the normothermia group (20% vs. 12%; relative likelihood, 1.54; 95% confidence interval [CI], 0.86 to 2.76; P=0.14). Among all the patients with data that could be evaluated, the change in the VABS-II score from baseline to 12 months was not significantly different (P=0.13) and 1-year survival was similar (38% in the hypothermia group vs. 29% in the normothermia group; relative likelihood, 1.29; 95% CI, 0.93 to 1.79; P=0.13). The groups had similar incidences of infection and serious arrhythmias, as well as similar use of blood products and 28-day mortality.In comatose children who survived out-of-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a good functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; THAPCA-OH ClinicalTrials.gov number, NCT00878644.).
The role of beliefs: lessons from a pilot study on illness perception, psychological distress and quality of life in patients with primary cicatricial alopecia
Authors: Y.Z. Chiang, C. Bundy, C.E.M. Griffiths, R. Paus, M.J. Harries
Journal: British Journal of Dermatology (2014)

Background While alopecia has been shown to have substantial psychological consequences, previous studies have not explicitly explored the key beliefs of patients with primary cicatricial alopecia (PCA) and the relationship between clinical and psychological measures. Objectives To identify the key psychological factors and quality of life (QoL) of patients with PCA and the relationship between these factors and established clinical measures. Methods In total 105 patients with PCA were recruited from a specialist hair research clinic in Manchester, U.K. Patients completed the revised Illness Perception Questionnaire, Hospital Anxiety and Depression Scale (HADS) and Dermatology Life Quality Index. These psychological measures were correlated with disease activity in patients with lichen planopilaris (LPP) and frontal fibrosing alopecia, using the LPP Activity Index (LPPAI). Results Patients perceived PCA as a chronic condition with significant personal consequences and emotional impact, and reported that they had low levels of control over the condition and its treatment. Considerable levels of psychological distress were observed (mean HADS total score 11·3 ± 8·1). Impaired QoL was associated with strong beliefs that the symptoms were attributed to their disease (P < 0·001), and that alopecia had serious consequences (P < 0·001) and was distressing (P < 0·001). Disease activity (LPPAI) showed a significant positive correlation with HADS-Depression (r = 0·343, P = 0·026). Conclusions Patients with PCA experience significant psychological distress and impaired QoL, both of which are associated with key beliefs about illness. Management of PCA should involve assessment of the beliefs and emotions that drive patients' psychological distress, as well as giving access to psychological therapy.
Diabetes Impairs Hematopoietic Stem Cell Mobilization by Altering Niche Function
Authors: Francesca Ferraro, Stefania Lymperi, Simón Méndez-Ferrer, Borja Saez, Joel A. Spencer, Beow Y. Yeap, Elena Masselli, Gallia Graiani, Lucia Prezioso, Elisa Lodi Rizzini, Marcellina Mangoni, Vittorio Rizzoli, Stephen M. Sykes, Charles P. Lin, Paul S. Frenette, Federico Quaini, David T. Scadden
Journal: Science Translational Medicine (2011)

Impaired mobilization of hematopoietic stem cells in diabetic mice is due to sympathetic nervous system dysregulation of CXCL12 distribution.
Uncommonly common? Common variable immunoglobulin deficiency 'masquerading' as sarcoidosis
Authors: Ratna Alluri, David Miller, Anne-Marie Shanks, Richard Herriot, Owen Dempsey
Journal: European Respiratory Journal (2012)

Introduction :

Multisystem granulomatous inflammation can be a presenting feature or a complication of common variable immune deficiency (CVID).A proportion of patients diagnosed with 'sarcoidosis' may actually have underlying CVID, recognition of which may be associated with considerable diagnostic delay.

Method : 2 cases are presented to illustrate this along the results of an audit.

Case 1 

LC presented aged 28 with chronic cough and deranged LFTs. HRCT showed multiple pulmonary nodules and generalised lymphadenopathy.Granulomas were seen on liver biopsy.A diagnosis of sarcoidosis was made.4 years later after several chest infections, severe panhypogammaglobulinemia was demonstrated and a revised diagnosis of CVID made.

Case 2 

DG presented aged 29 with cough, breathlessness and generalised lymphadenopathy with bilateral hilar lymphadenopathy on chest x-ray.Sarcoidosis was diagnosed after lymph node aspirate demonstrated granulomata.13 years later, investigations after a protracted pneumonia revealed panhypogammaglobulinemia.

Standard immunoglobulin replacement therapy at a dose of 400mg/kg/month was started in both cases after the diagnosis of CVID.

An audit of our cohort of 148 patients with diagnosed sarcoidosis found that 47% had not had serum immunoglobulins checked during diagnostic work-up.

Conclusion: 

Chest physicians often omit to check immunoglobulins when assessing patients with suspected sarcoidosis.This may not be surprising given the lack of advice on measurement of immunoglobulins in current Interstitial Lung Disease guidelines. While CVID is uncommon, awareness, early diagnosis and effective treatment can reduce morbidity, mortality and complications and improve quality of life.
Airway re-narrowing following deep inspiration in asthmatic and nonasthmatic subjects
Authors: C.M. Salome, C.W. Thorpe, C. Diba, N.J. Brown, N. Berend, G.G. King
Journal: European Respiratory Journal (2003)

After bronchoconstriction, deep inspiration (DI) causes dilatation followed by airway re-narrowing. Re-narrowing may be faster in asthmatic than nonasthmatic subjects. This study investigated the relationship between re-narrowing and the magnitude of both DI-induced dilatation and the volume-dependence of respiratory system resistance ( R rs ) during tidal breathing. In 25 asthmatic and 18 nonasthmatic subjects the forced oscillation technique was used to measure R rs at baseline and after methacholine challenge, during 1 min of tidal breathing, followed by DI to total lung capacity (TLC) and passive return to functional residual capacity (FRC). Dilatation was measured as the decrease in R rs between end tidal inspiration and TLC, re-narrowing as R rs at FRC immediately after DI, as per cent R rs at end-tidal expiration, and volume dependent tidal fluctuation as the difference between mean R rs at end-expiration and end-inspiration. Asthmatic subjects had greater re-narrowing, less dilatation, and greater tidal fluctuations both at baseline and after challenge. Re-narrowing correlated with baseline tidal fluctuation and inversely with dilatation. Both baseline tidal fluctuation and dilatation were significant independent predictors of re-narrowing. Following deep inspiration-induced dilatation, faster airway re-narrowing in asthmatic than nonasthmatic subjects is associated not only with reduced deep inspiration-induced dilatation but also with some property of the airways that is detectable prior to challenge as an increased volume dependence of resistance.
INFECTIOUS MOTOR PARALYSIS IN YOUNG RABBITS
Authors: J. Homer Wright, Eugene M. Craighead
Journal: The Journal of Experimental Medicine (1922)

1. The attempt to infect young rabbits and guinea pigs with material containing in all probability the virus of human infantile paralysis failed. 2. Failure to infect the primary animals almost of necessity brought failure with the secondary flea-bitten animals. It is, however barely conceivable that a non-infectious form of an organism might circulate in the blood of the primary animal and that this form, through development in an intermediate host, the flea, might become virulent for the secondary flea-bitten animal. 3. Incidentally, and presumably accidentally, a paralytic disease was observed in young rabbits associated with the presence of an organism showing certain definite characters. So far as we know this paralysis and the associated organism have not been previously described. 4. This organism is found widely distributed in the organs of the affected animals and can be demonstrated in the urine. The active destruction by the organism of the nerve cells of the spinal cord is particularly striking, and gives complete explanation for the paralysis observed clinically. 5. With the organism present in the urine the spread of the disease by contact can be easily understood. 6. The transfer of the infection from animal to animal by fleabites is possible but not probable. 7. The nature of the observed organisms is in doubt. They represent probably an intermediate stage in the life history of some protozoan parasite.
Circulating Carotenoids, Mammographic Density, and Subsequent Risk of Breast Cancer
Authors: Rulla M. Tamimi, Graham A. Colditz, Susan E. Hankinson
Journal: Cancer Research (2009)

Mammographic density is one of the strongest predictors of breast cancer risk. Recently, it has been suggested that reactive oxygen species may influence breast cancer risk through its influence on mammographic density. In the current study, we addressed this hypothesis and also assessed if the association between carotenoids and breast cancer risk varies by mammographic density. We conducted a nested case-control study consisting of 604 breast cancer cases and 626 controls with prospectively measured circulating carotenoid levels and mammographic density in the Nurses' Health Study. Circulating levels of alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin were measured. We used a computer-assisted thresholding method to measure percent mammographic density. We found no evidence that circulating carotenoids are inversely associated with mammographic density. However, mammographic density significantly modified the association between total circulating carotenoids and breast cancer (P heterogeneity = 0.008). Overall, circulating total carotenoids were inversely associated with breast cancer risk (P trend = 0.01). Among women in the highest tertile of mammographic density, total carotenoids were associated with a 50% reduction in breast cancer risk (odds ratio, 0.5; 95% confidence interval, 0.3-0.8). In contrast, there was no inverse association between carotenoids and breast cancer risk among women with low mammographic density. Similarly, among women in the highest tertile of mammographic density, high levels of circulating alpha-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin were associated with a significant 40% to 50% reduction in breast cancer risk (P trend < 0.05). Our results suggest that plasma levels of carotenoids may play a role in reducing breast cancer risk, particularly among women with high mammographic density.
Changes in levels of catalase and glutathione in erythrocytes of patients with stable asthma, treated with beclomethasone dipropionate
Authors: HJ Pennings, PJ Borm, CT Evelo, EF Wouters
Journal: European Respiratory Journal (1999)

In asthmatic patients, antioxidant defence is decreased. Although inhaled corticosteroids decrease asthmatic inflammation and modulate reactive oxygen species (ROS) generation, little is known of their effect on cellular antioxidant levels. The aim of this study was to evaluate the effect of inhaled beclomethasone dipropionate (BDP; 1,000 microg x day(-1)) on erythrocyte antioxidant levels in stable asthmatic patients. Forty patients with stable, mild asthma were treated in a double-blind, placebo-controlled, parallel-group study with BDP 250 microg, two puffs b.i.d. for 6 weeks. At entry and every 2 weeks during treatment, erythrocyte antioxidant levels, haematological parameters, pulmonary function tests and asthma symptoms were determined. The results show that during treatment with BDP, erythrocyte catalase levels increased (at entry (mean +/-SEM) 41+/-4, after 6 weeks 54+/-4 micromol H2O2 x min(-1) x g haemoglobin (Hb)(-1), p = 0.05 in comparison with placebo). Erythrocyte total glutathione levels significantly decreased after 6 weeks treatment with BDP (from 7.0+/-0.4 to 6.6+/-0.3 micromol x g Hb(-1) (p = 0.04)). In the BDP-treated patients, blood eosinophil counts were higher in patients who responded with an increase in erythrocyte catalase levels during BDP treatment, as compared to those not responding ((mean +/-SEM) 340+/-39 and 153+/-52x10(6) cells x L(-1), respectively, p = 0.05). The present study shows that treatment with inhaled bedomethasone dipropionate results in changes in antioxidant levels in erythrocytes of patients with stable, mild asthma.
Organising pneumonia caused by transtuzumab (Herceptin) therapy for breast cancer
Authors: E. Radzikowska, E. Szczepulska, M. Chabowski, I. Bestry
Journal: European Respiratory Journal (2003)

The case of a 49-yr-old female, who developed fever, effort dyspnoea and cough, with patchy migratory bilateral pulmonary infiltrates 6 weeks after starting transtuzumab therapy, following breast-conserving surgery with adjuvant chemoradiotherapy and hormone therapy for breast carcinoma, is reported here. Chest radiograph and thin section computed tomography demonstrated alveolar opacities with air bronchogram in both lungs. A lung biopsy was performed in a nonirradiated area of the contralateral lung and revealed a typical histological pattern of organising pneumonia (previously known as bronchiolitis obliterans organising pneumonia). Transtuzumab therapy was discontinued and subsequent gradual clinical and radiological improvement was observed. After 3 months, complete resolution of symptoms and radiographical abnormalities were noted. This is the first case report that suggests that transtuzumab therapy might induce the development of lung infiltrates with the histological appearance of organising pneumonia.
Distinct Role of cAMP and cGMP in the Cell Cycle Control of Vascular Smooth Muscle Cells
Authors: Shinya Fukumoto, Hidenori Koyama, Masayuki Hosoi, Kenjiro Yamakawa, Shinji Tanaka, Hirotoshi Morii, Yoshiki Nishizawa
Journal: Circulation Research (1999)

cAMP and cGMP are known to suppress vascular smooth muscle cell (SMC) proliferation. In this study, our aim was to delineate the molecular mechanism underlying cAMP and cGMP suppression of cell cycle transition in human SMCs. cAMP inhibits both platelet-derived growth factor-stimulated cyclin-dependent kinase (cdk) 2 and cdk4 activation through upregulation of the cdk2 inhibitor p27(Kip1) and downregulation of cyclin D1 expression, which leads to a complete arrest of the cells in phase G(1). In contrast, cGMP inhibits cyclin D1 expression, inhibits cdk4 activation, and delays platelet-derived growth factor-mediated cdk2 activation, resulting in a delay in G(1)/S transition. A transient increase in p27(Kip1) in cdk2 immunoprecipitates, without changes in total cellular p27(Kip1) levels, correlates with the delay in cdk2 activation caused by cGMP. Thus, cAMP and cGMP differentially affect cell cycle through distinct regulation of cell cycle molecules in human SMCs.
A Prospective Evaluation of a Protocol for Magnetic Resonance Imaging of Patients With Implanted Cardiac Devices
Authors: Saman Nazarian, Rozann Hansford, Ariel Roguin, Dorith Goldsher, Menekhem M. Zviman, Albert C. Lardo, Brian S. Caffo, Kevin D. Frick, Michael A. Kraut, Ihab R. Kamel, Hugh Calkins, Ronald D. Berger, David A. Bluemke, Henry R. Halperin
Journal: Annals of Internal Medicine (2011)

Background: Magnetic resonance imaging (MRI) is avoided in most patients with implanted cardiac devices because of safety concerns. Objective: To define the safety of a protocol for MRI at the commonly used magnetic strength of 1.5 T in patients with implanted cardiac devices. Design: Prospective nonrandomized trial. (ClinicalTrials.gov registration number: NCT01130896) Setting: One center in the United States (94% of examinations) and one in Israel. Patients: 438 patients with devices (54% with pacemakers and 46% with defibrillators) who underwent 555 MRI studies. Intervention: Pacing mode was changed to asynchronous for pacemaker-dependent patients and to demand for others. Tachyarrhythmia functions were disabled. Blood pressure, electrocardiography, oximetry, and symptoms were monitored by a nurse with experience in cardiac life support and device programming who had immediate backup from an electrophysiologist. Measurements: Activation or inhibition of pacing, symptoms, and device variables. Results: In 3 patients (0.7% [95% CI, 0% to 1.5%]), the device reverted to a transient back-up programming mode without long-term effects. Right ventricular (RV) sensing (median change, 0 mV [interquartile range {IQR}, −0.7 to 0 V]) and atrial and right and left ventricular lead impedances (median change, −2 Ω [IQR, −13 to 0 Ω], −4 Ω [IQR, −16 to 0 Ω], and −11 Ω [IQR, −40 to 0 Ω], respectively) were reduced immediately after MRI. At long-term follow-up (61% of patients), decreased RV sensing (median, 0 mV, [IQR, −1.1 to 0.3 mV]), decreased RV lead impedance (median, −3 Ω, [IQR, −29 to 15 Ω]), increased RV capture threshold (median, 0 V, IQR, [0 to 0.2 Ω]), and decreased battery voltage (median, −0.01 V, IQR, −0.04 to 0 V) were noted. The observed changes did not require device revision or reprogramming. Limitations: Not all available cardiac devices have been tested. Long-term in-person or telephone follow-up was unavailable in 43 patients (10%), and some data were missing. Those with missing long-term capture threshold data had higher baseline right atrial and right ventricular capture thresholds and were more likely to have undergone thoracic imaging. Defibrillation threshold testing and random assignment to a control group were not performed. Conclusion: With appropriate precautions, MRI can be done safely in patients with selected cardiac devices. Because changes in device variables and programming may occur, electrophysiologic monitoring during MRI is essential. Primary Funding Source: National Institutes of Health.
Targeting the Phosphatidylinositol 3-Kinase Pathway in Multiple Myeloma
Authors: Hashem Younes, Xavier Leleu, Evdoxia Hatjiharissi, Anne-Sophie Moreau, Teru Hideshima, Paul Richardson, Kenneth C. Anderson, Irene M. Ghobrial
Journal: Clinical Cancer Research (2007)

Abstract Multiple myeloma is a plasma cell neoplasm with a median survival of 3 to 5 years. Recent advances have improved patient outlook, but the disease remains incurable. Therefore, continued efforts to develop new therapies that target aberrant signaling pathways are needed. The phosphatidylinositol 3-kinase pathway regulates apoptosis, cell cycle regulation, and tumor proliferation. This pathway is constitutively activated in multiple myeloma and its inhibition induces apoptosis. Advances in understanding the signaling cascades mediating proliferation and survival of multiple myeloma cells have markedly improved the treatment of this disease. In this article, we review the role of the phosphatidylinositol 3-kinase/Akt pathway in the pathogenesis of multiple myeloma and the potential therapeutic implications of targeting this pathway in the treatment of multiple myeloma.
Spread of Activity Through the Atrioventricular Node
Authors: ANTONIO PAES DE CARVALHO, DARCY F. DE ALMEIDA
Journal: Circulation Research (1960)

Electrophysiologic mapping experiments on the excitation of the A-V node of isolated rabbit heart have been performed with intracellular microelectrodes. An area of tissue showing peculiar physiologic characteristics was shown to coincide, at least in part, with the histologic A-V node and His bundle. Three functional regions have been determined in the physiologic mapping of the A-V node. The middle layer (N) shows signs of decremental conduction and is the site of the slowest propagation velocity in the A-V node. The other layers are transitional regions between the N layer and atrium (AN) or the His bundle (NH). The AN layer shows a progressively slower propagation velocity as the N region is approached. The same holds for the NH region. A precise correlation between these findings and the 3 existent histologic layers remains to be determined. The existence of an area of peculiar tissue just above the A-V valves and encircling the A-V orifice has been confirmed. This area is continuous with the AN layer of the functional A-V node and has been named the atrioventricular ring (AVR) on the assumption that it is a remnant of the embryonic A-V ring. Wenckebach cycles and A-V block of nodal origin are tentatively explained as resulting from increased decrement in the middle nodal layer (N).