tbuckley/cabot-search huggingface dataset:
Sildenafil improves heart rate variability, pulmonary hemodynamics and functional status in pulmonary arterial hypertension
Authors: Khrystyna Semen, Lyubomyr Solovey, Marta Vasyliv, Danylo Kaminskyy, Olha Yelisyeyeva, Ostap Yavorskiy
Journal: European Respiratory Journal (2014)

The aim:  to study changes of heart rate variability (HRV) in relationship with exercise tolerance, pulmonary hemodynamics and level of NT-proBNP in PAH patients receiving sildenafil.   Material and methods  .  Seven patients with severe idiopathic PAH (mean age 32±9years, 4 patients with FC ІІ and 3 patients with FC ІІІ) confirmed by right heart catheterization were given sildenafil (75 mg/d) for 12 weeks. Changes in the echocardiographic indexes, distance in 6-minute walk test (6MWT), NT-proBNP determined in blood, and HRV parameters from short-time ECG records were analyzed before and after the study.   Results.  Therapy with sildenafil caused some increase in 6-MWT (from 373.7±65.9 m to 401±49.3 m) with significant reduction of the tricuspid valve systolic pressure gradient (from 69±10 to 48±12 mmHg) confirmed by echocardiography. A decrease in NT-proBNP was more prominent in patients with its initial lower values. These changes were accompanied by marked increase in HRV time and frequency domain parameters after sildenafil treatment. Predominance of the very low and low frequency bands was preserved in spectral structure during study both in supine position and during orthostasis.   Conclusions  .  Sildenafil therapy was associated with significant increase in HRV, improvement of functional capacity and clinical status in PAH patients. Correlations between HRV, hemodynamic indexes and NT-proBNP levels are suggestive about great potential of HRV for disease course monitoring in PAH.
Rising burden of lung cancer in non-smoking females in Kandy, Sri Lanka
Authors: Dushantha Madegedara, Duminda Yasaratne, Damith Nandadeva, Milanka Wattegama, Samudani Dhanasekara
Journal: European Respiratory Journal (2013)

Background  Incidence of female lung cancer in Sri Lanka is steadily rising.    Aim  To identify the demography and histology patterns of lung cancer in a non-smoking female population.    Setting  Respiratory Unit, Teaching Hospital Kandy, Sri Lanka    Method  Retrospective study using bronchoscopy database 2011-12. Case definition criteria were positive evidence of malignancy in cytology/histology.    Results  Of 98 lung cancers diagnosed and referred to oncology over the two years, 43 (44%) were females. Despite strong radiological evidence, six of them could not be confirmed due to technical difficulties. Bronchoscopy showed macroscopic tumour in 32 (86%) at carina (2), main bronchi (4), lobar bronchi (9) and segmental bronchi (17).  Of 37 diagnosed females (mean age of 58.6; range 31-96 yrs) three (8%) had metastatic disease from breast, colon and unknown site respectively. Of 34 (92%) primary lung cancers, non-small cell lung cancer (NSCLC,28), small cell lung cancer (SCLC,2) and poorly differentiated lung cancer (2) were diagnosed. Of NSCLC, ten were of squamous origin, while adeno carcinoma (6) and undifferentiated NSCLC (12) were seen.    Discussion  None were smokers nor had significant passive smoking exposure. However firewood usage in Kandy is 83% (Perera et al. Symposium on air resource management, Sri Lanka 2004). Environmental statistics recently identified Kandy as a city with significant air pollution, owing to its geography and motor traffic (Nandasena et al. BMC Public Health 2010,10:300).    Conclusion  This retrospective analysis reveals an alarming incidence of NSCLC among non-smoking females in Kandy. Future studies should aim to identify causal relationship of non-conventional risk factors.
Structure and Development of the Herpes-Type Virus of Marek's Disease&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M. A. Epstein, B. G. Achong, A. E. Churchill, P. M. Biggs
Journal: JNCI Journal of the National Cancer Institute (1968)

Chicken kidney cultures infected with eight different strains of Marek's disease were investigated with the electron microscope for virus. The cultured cells were epithelial in nature and a typical herpes-type virus was found after infection with each strain; no virus was present in uninoculated control cultures. In each case the virus was morphologically indistinguishable, with hexagonal immature particles in both the nucleus and cytoplasm; the virus matured by budding at the nuclear envelope and cytoplasmic vacuoles to form larger mature particles. In negative-contrast preparations the capsid structure and surface configuration of the immature particles were also typical of the herpes group of viruses. Virus-infected cells showed characteristic cytopathological changes including sheaves of altered spindle tubules. The significance of a herpes-type virus in an animal lymphoma is discussed relative to the herpes-type EB virus associated with the Burkitt lymphoma.
Analyzing the pathway to triple therapy in COPD patients: A retrospective database analysis
Authors: David Price, Rupert Jones, Kevin Gruffydd-Jones, Guy Brusselle, Marc Miravitlles, Michael Baldwin, Rebecca Stewart, Dorothy L. Keininger
Journal: European Respiratory Journal (2014)

Introduction 

Real-world prescription pathways leading to triple therapy (TT; ICS+LABA+LAMA) may differ from the current GOLD treatment recommendations. This study identified non-asthmatic COPD patients receiving TT, and pathways taken from diagnosis to first TT prescription.

Methods 

Retrospective analysis from the Optimum Patient Care Research Database (387 primary care practices across UK) was done. We included non-asthmatic patients from 2002-2010 with valid data 1 year prior to COPD diagnosis, and at least 2 years post-diagnosis, classified on GOLD 2014 criteria (mMRC, FEV1 and exacerbations; not CAT). Data was analyzed for use of TT prior to/at/after diagnosis, including the average time taken to TT.

Results 

Data from 11,858 patients were analyzed. At time of diagnosis patients were classified as GOLD A (41.2%), B (24.7%), C (17.3%) and D (16.8%). 31.7% received TT during study period: 1.5% received TT prior to initial diagnosis; 1.4% at diagnosis and 28.8% (n=3414) progressed to TT after initial diagnosis. 18.9%, 27.6%, 36.8% and 46.4% of patients classified GOLD A, B, C, D, respectively at diagnosis (p<0.001) reached TT after diagnosis. 25.2% of patients progressing to TT reached TT within 1 year of diagnosis; 26.1%, 21.7%, 24.3% and 28.0% of patients classified GOLD A, B, C, D groups at diagnosis and reaching TT respectively (p=0.065).

Conclusion 

The GOLD strategy recommends ICS use combined with LABA or LAMA in GOLD C patients and TT (ICS+LABA+LAMA) in GOLD D patients. However, real world prescription pathways demonstrate inappropriate TT prescription for upto a quarter of patients after initial diagnosis and others progress to TT within 1 year of diagnosis, regardless of GOLD category.
Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration
Authors: V. Bossuyt, E. Provenzano, W.F. Symmans, J.C. Boughey, C. Coles, G. Curigliano, J.M. Dixon, L.J. Esserman, G. Fastner, T. Kuehn, F. Peintinger, G. von Minckwitz, J. White, W. Yang, S. Badve, C. Denkert, G. MacGrogan, F. Penault-Llorca, G. Viale, D. Cameron, Helena Earl, Emilio Alba, Ana Lluch, Joan Albanell, Keith Amos, Wojciech Biernat, Hervé Bonnefoi, Aman Buzdar, Paul Cane, Sarah Pinder, Lesley Carson, Diana Dickson-Witmer, Gyungyub Gong, Jimmy Green, Chih-Yi Hsu, Ling-Ming Tseng, Judith Kroep, A. Marilyn Leitch, Venetia Sarode, Eleftherios Mamounas, Paul Kelly Marcom, Paolo Nuciforo, Soonmyung Paik, Vicente Peg, David Peston, Jean-Yves Pierga, Miguel Quintela-Fandino, Roberto Salgado, William Sikov, Jeremy Thomas, Gary Unzeitig, Jelle Wesseling
Journal: Annals of Oncology (2015)
Second Cancers Following Radiation Treatment for Cervical Cancer. An International Collaboration Among Cancer Registries
Authors: J D Boice, N E Day, A Andersen, L A Brinton, R Brown, N W Choi, E A Clarke, M P Coleman, R E Curtis, J T Flannery
Journal: JNCI Journal of the National Cancer Institute (1985)

The numbers of second cancers among 182,040 women treated for cervical cancer that were reported to 15 cancer registries in 8 countries were compared to the numbers expected had the same risk prevailed as in the general population. A small 9% excess of second cancers (5,146 observed vs. 4,736 expected) occurred 1 or more years after treatment. Large radiation doses experienced by 82,616 women did not dramatically alter their risk of developing a second cancer; at most, about 162 of 3,324 second cancers (≈5%) could be attributed to radiation. The relative risk (RR = 1.1) for developing cancer in organs close to the cervix that had received high radiation exposures—most notably, the bladder, rectum, uterine corpus, ovary, small intestine, bone, and connective tissue—and for developing multiple myeloma increased with time since treatment. No similar increase was seen for 99,424 women not treated with radiation. Only a slight excess of acute and non-lymphocytic leukemia was found among irradiated women (RR = 1.3), and substantially fewer cases were observed than expected on the basis of current radiation risk estimates. The small risk of leukemia may be associated with low doses of radiation absorbed by the bone marrow outside the pelvis, inasmuch as the marrow in the pelvis may have been destroyed or rendered inactive by very large radiotherapy exposures. There was little evidence of a radiation effect for cancers of the stomach, colon, liver, and gallbladder, for melanoma and other skin cancers, or for chronic lymphocytic leukemia despite substantial exposures. An excess of thyroid cancer possibly was related to the low dose received by this organ. Ovarian damage caused by radiation may have been responsible for a low breast cancer risk (RR=0.7), which was evident even among postmenopausal women. A substantial excess of lung cancer (RR=3.7) largely may be due to misclassification of metastases and the confounding influence of cigarette smoking. Women who were under 30 or over 50 years of age when irradiated were at greatest absolute risk for developing a second cancer. The RR, however, was higher among those under age 30 years at exposure (RR=3.9) than among older women. The expression period for radiation-induced solid tumors appeared to continue to the end of life.
Traffic-related Air Pollution and Lung Function in Children at 8 Years of Age
Authors: Erica S. Schultz, Olena Gruzieva, Tom Bellander, Matteo Bottai, Jenny Hallberg, Inger Kull, Magnus Svartengren, Erik Melén, Göran Pershagen
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Long-term exposure to air pollution has been related to lung function decrements in children, but the role of timing of exposure remains unknown.Objectives: To assess the role of long-term exposure to air pollution on lung function in school-age children.Methods: More than 1,900 children in the Swedish birth cohort BAMSE were followed with repeated questionnaires, dynamic spirometry, and IgE measurements until 8 years of age. Outdoor concentrations of particulate matter with an aerodynamic diameter less than 10 μm (PM10) from road traffic were estimated for residential, day care, and school addresses from birth and onward using dispersion modeling. The relationship between time-weighted average exposure during different time windows and FEV at 8 years was analyzed by linear regression, adjusting for potential confounding factors, including short-term exposure to air pollution.Measurements and Main Results: A 5th to 95th percentile difference in time-weighted average particulate matter less than 10 μm in aerodynamic diameter exposure during the first year of life was associated with a reduced FEV1 of −59.3 ml (95% confidence interval, −113 to −5.6) at 8 years of age. The negative association was particularly pronounced in children concomitantly sensitized to common inhalant or food allergens (−136.9 ml; 95% confidence interval, −224.1 to −49.7). Exposure after the first year of life seemed to have less impact on lung function at 8 years.Conclusions: Our results indicate that exposure to traffic-related air pollution during infancy affects lung function in children up to 8 years of age and particularly in those sensitized to common inhalant or food allergens.
In vivo effects of corticosteroid plus long-acting beta2-agonist on the expression of B7-H1/PD-L1 in double-stranded RNA-induced lung inflammation
Authors: Saaka Hamano, Koichiro Matsumoto, Satoru Fukuyama, Keiko Kan-o, Nanae Seki, Ken Tonai, Takako Nakano, Hiromasa Inoue, Yoichi Nakanishi
Journal: European Respiratory Journal (2014)

Background and Aim: Airway viral infection exacerbates asthma and COPD. B7-H1/PD-L1 is a coinhibitory molecule implicated in an escape mechanism of viruses from the host immune systems. This escape may induce viral persistence and lead to the exacerbation. In ERS international congress 2013, we showed that an analog of viral double-strand RNA, polyinosinic-polycytidylic acid (poly I:C), upregulated the expression of B7-H1/PD-L1 on airway epithelial cells in vitro, which was resistant to corticosteroid treatment. Although this resistance was overcome by addition of long-acting beta2-agonist (LABA), in vivo evidence remained uncertain. We examined the effect of corticosteroid plus LABA on the expression of B7-H1/PD-L1 in vivo.  Methods: We established a murine model of double-stranded RNA-induced inflammation by an intratracheal administration (i.t.) of poly I:C. The expression of B7-H1/PD-L1 in epithelial cells was assessed by flow cytometry as well as assessment of inflammation in bronchoalveolar lavage fluid (BALF). The effects of ciclesonide and/or indacaterol (i.t.) were examined.  Results: Poly I:C induced upregulation of B7-H1/PD-L1 in epithelial cells and neutrophilia in BALF. The upregulation was suppressed by low-concentration ciclesonide in combination with indacaterol. This combination also suppressed neutrophilia in BALF.  Conclusion: Corticosteroid plus LABA attenuates double-stranded RNA-induced upregulation of B7-H1/PD-L1 in vivo. This mechanism may partly explain a beneficial effect of combination therapy on virus-associated exacerbation of asthma and COPD.
Hypoxaemia and liver cirrhosis: a new argument in favour of a "diffusion-perfusion defect"
Authors: JB Thorens, AF Junod
Journal: European Respiratory Journal (1992)

Liver cirrhosis is sometimes associated with very severe hypoxaemia, which is thought to be the result of intrapulmonary vascular dilatations (IPVDs). These vascular abnormalities, although close to the gas exchange units, are so dilated that diffusion of oxygen molecules to their centre is impaired, causing an increase in alveolar-arterial oxygen tension difference (P(A-a)O2). On the other hand, administration of 100% oxygen provides enough driving pressure to overcome this relative diffusion defect and rules out a true intrapulmonary shunt. We report a case in which, in spite of a normal increase in arterial oxygen tension (PaO2) under 100% oxygen, exercising results in a marked impairment of oxygen exchange and a large intrapulmonary shunt. This is probably due to the increased cardiac output and preferential blood flow through these low resistance IPVDs.
Transcatheter Aortic Valve Replacement
Authors: Stefan Toggweiler, Robert H. Boone, Josep Rodés-Cabau, Karin H. Humphries, May Lee, Luis Nombela-Franco, Rodrigo Bagur, Alexander B. Willson, Ronald K. Binder, Ronen Gurvitch, Jasmine Grewal, Robert Moss, Brad Munt, Christopher R. Thompson, Melanie Freeman, Jian Ye, Anson Cheung, Eric Dumont, David A. Wood, John G. Webb
Journal: Journal of the American College of Cardiology (2012)
Neoadjuvant chemotherapy for low-grade serous carcinoma of the ovary
Authors: K. M. Schmeler, C. C. Sun, D. C. Bodurka, M. T. Deavers, R. L. Coleman, P. T. Ramirez, D. M. Gershenson
Journal: Journal of Clinical Oncology (2007)

5571 Background: Neoadjuvant chemotherapy (NACT) has been associated with significant tumor reduction prior to interval debulking surgery, enabling optimal cytoreduction in up to 50% of patients with high-grade ovarian carcinomas deemed initially unresectable. Since low-grade serous carcinoma (LGSC) appears to be relatively less chemosensitive, we sought to evaluate the outcomes of women with ovarian LGSC treated with platinum-based NACT. Methods: Using institutional databases, we identified 18 women with low-grade serous carcinomas of the ovary who were treated with neoadjuvant platinum-based chemotherapy between 1978 and 2003. Patient demographic and clinical variables were abstracted from the medical records. Progression-free survival (PFS) and overall survival (OS) were estimated using the method of Kaplan-Meier. Results: The median age at diagnosis was 44 years (range, 21 to 81 years). NACT was given for extensive or non-resectable disease in 16 patients (89%) and for unknown reasons in 2 patients (11%). Ten patients (42%) underwent exploratory laparotomy with biopsy only prior to beginning chemotherapy. A median of 6 cycles of chemotherapy was given (range, 2 to 16) and included the following regimens: platinum/taxane (n=12 patients); platinum/cyclophosphamide (n=3 patients); and platinum/leuprolide acetate (n=3 patients). Of the 13 patients who had CA-125 levels available, 8 (62%) had a ≥50% reduction between pre- and post-NACT levels. However, response, determined by radiographic survey at completion of NACT, demonstrated one patient (6%) with a complete response, no patients (0%) with a partial response, and 16 patients (89%) with stable disease. One patient (6%) was not evaluable. Fifteen patients (83%) underwent interval cytoreductive surgery, which was optimal in 8 cases (53%), suboptimal in 4 cases (27%) and unknown in 3 cases (20%). Median PFS and OS for all patients were 18.6 and 56.1 months, respectively. Conclusions: A low response rate to platinum-based NACT was observed among women with LGSC of the ovary. These findings suggest that LGSC is not as responsive to conventional chemotherapy as high-grade serous carcinoma. Prospective clinical trials, focusing specifically on LGSC, are needed to make meaningful advances for this group of patients. No significant financial relationships to disclose.
How does Bladder Function Change in the Early Period after Surgical Alteration in Outflow Resistance?: Preliminary Communication
Authors: M J Coptcoat, P J R Shah, J Cumming, C Charig, P H L Worth
Journal: Journal of the Royal Society of Medicine (1987)

A decrease in voiding pressures because of decreased outflow resistance has been demonstrated in 8 males, and conversely an increase in voiding pressures because of increased outflow resistance has been demonstrated in 7 females undergoing surgery. These changes occur in the early postoperative period.
Optimizing Endocrine Therapy for Breast Cancer
Authors: Amelia B. Zelnak, Ruth M. O'Regan
Journal: Journal of the National Comprehensive Cancer Network (2015)

Endocrine therapy has significantly improved outcomes for patients with early- and advanced-stage hormone-receptor (HR)–positive breast cancer. Despite the success of adjuvant endocrine therapy, some patients with early-stage disease will experience relapse. Additionally, all patients with advanced disease will eventually experience disease progression on endocrine therapy due to resistance. Improved understanding of the mechanisms associated with resistance to endocrine agents has recently led to the approval of new therapeutics. Multiple questions remain unanswered, including the optimal duration of adjuvant therapy, the role of ovarian ablation in early-stage breast cancer in premenopausal women, and how to best incorporate targeted agents with endocrine therapy in the metastatic setting. This article reviews the optimization of endocrine therapy in patients with HR-positive breast cancer, focusing on these controversial areas.
Comparative Characterization of Iron Deposits in Spleens and Livers of Malaria and Schistosoma Infected Mice
Authors: Lucia Gutierrez, Stephan Karl, Rina P. M. Wong, Rafael Lucyk Maurer, Shu Q. Toh, Renata R. F. Candido, Anita Chua, Robert C. Woodward, Martin Saunders, Jeremy Shaw, Michael House, Carlos Graeff-Teixera, Malcolm K. Jones, Timothy M. E. Davis, Timothy G. St Pierre
Journal: American Journal of Hematology (2013)

Poster presented at Fifth Congress of the International BioIron Society that took place in University College London (London, United Kingdom) during 14-18th April 2013.
A Longitudinal Study of Resting Heart Rate and Violent Criminality in More Than 700 000 Men
Authors: Antti Latvala, Ralf Kuja-Halkola, Catarina Almqvist, Henrik Larsson, Paul Lichtenstein
Journal: JAMA Psychiatry (2015)

Low resting heart rate is a well-replicated physiological correlate of aggressive and antisocial behavior in children and adolescents, but whether low resting heart rate increases the risk of violence and other antisocial and risk-taking behaviors in adulthood has not been studied in representative samples.To study the predictive association of resting heart rate with violent and nonviolent criminality and with fatal and nonfatal injuries owing to assaults and unintentional injuries in the population.We conducted a study of data from several Swedish national registers on 710 264 Swedish men in the general population born from 1958 to 1991, with a follow-up of up to 35.7 years. Outcome data were available and analyzed from January 1, 1973, through December 31, 2009. Resting heart rate was measured together with blood pressure at mandatory military conscription testing at a mean (SD) age of 18.2 (0.5) years.Violent and nonviolent criminal convictions and medical treatments or deaths owing to assaults and unintentional injuries.In models adjusted for physical, cardiovascular, psychiatric, cognitive, and socioeconomic covariates, compared with 139 511 men in the highest quintile of the distribution of resting heart rate (≥83 beats/min), 132 595 men with the lowest quintile (heart rate, ≤60 beats/min) had a 39% (95% CI, 35%-44%) higher hazard of being convicted of violent crimes and a 25% (95% CI, 23%-28%) higher hazard of being convicted of nonviolent crimes. The corresponding hazard was 39% higher for assault injuries (95% CI, 33%-46%) and for unintentional injuries (95% CI, 38%-41%). Further adjustment for cardiorespiratory fitness in a subset of 572 610 men with data from an exercise test did not reduce the associations. Similar associations were found between low systolic blood pressure and violent and nonviolent criminality and for assault injuries when systolic blood pressure was studied instead of resting heart rate in more than 1 million men.Among men, low resting heart rate in late adolescence was associated with an increased risk for violent criminality, nonviolent criminality, exposure to assault, and unintentional injury in adulthood. Most of these results were replicated with low systolic blood pressure. Resting heart rate and other autonomic measures merit further study in the development and prevention of violence and antisocial behavior.
CAR therapy: the CD19 paradigm
Authors: Michel Sadelain
Journal: Journal of Clinical Investigation (2015)

Twenty-five years after its inception, the genetic engineering of T cells is now a therapeutic modality pursued at an increasing number of medical centers. This immunotherapeutic strategy is predicated on gene transfer technology to instruct T lymphocytes to recognize and reject tumor cells. Chimeric antigen receptors (CARs) are synthetic receptors that mediate antigen recognition, T cell activation, and - in the case of second-generation CARs - costimulation to augment T cell functionality and persistence. We demonstrated over a decade ago that human T cells engineered with a CD19-specific CAR eradicated B cell malignancies in mice. Several phase I clinical trials eventually yielded dramatic results in patients with leukemia or lymphoma, especially acute lymphoblastic leukemia (ALL). This review recounts the milestones of CD19 CAR therapy and summarizes lessons learned from the CD19 paradigm.