tbuckley/cabot-search huggingface dataset:
Validation of a portable lung volume testing system
Authors: Victoria Batsford, James Stockley, Brendan Cooper
Journal: European Respiratory Journal (2014)

Aim:  We wanted to validate the ndd Easy One Pro Lab Plus for static lung volumes using multiple breath nitrogen washout (MBW) technique, against standard helium dilution (HD) equipment.   Method:  We tested healthy volunteers (n=16) and routine respiratory patients (n=22) [Mean (SD) Age (years) 44.1 (17.8); Height (m) 1.66 (0.10); M:F 12:26) by both MBW (Easy One Pro Lab Plus, ndd, Zurich, Switzerland) and HD (Jaeger Masterscreen PFT, Hochburg, Germany) and compared Functional Residual Capacity (FRC), Residual Volume (RV) and Total Lung Capacity (TLC) using student9s paired t-test and Bland & Altman (B&A) analysis.   Results:  There was no significant difference in TLC, FRC or RV between MBW and HD (Table 1).  The B&A analysis (Fig 1.) shows that the difference in RV was homoscedastic and not clinically significant. This was similar in FRC and RV (see table).   Conclusion:  There was no clinically significant difference (all
Patient-Reported Outcomes in Multiple Myeloma
Authors: Stephanie J. Lee
Journal: Journal of the National Comprehensive Cancer Network (2004)

Multiple myeloma is an incurable malignancy of plasma cells. People with multiple myeloma may experience a variety of disease-related symptoms because of bony destruction, bone marrow infiltration, renal failure, immunodeficiency, and the psychosocial burden of a cancer diagnosis. Exciting new therapies and treatment approaches are becoming available but often bring unwanted side effects. Because the goal of treating multiple myeloma is still symptom palliation and prolongation of life rather than cure, it is important to consider the tradeoffs between treatment toxicity and disease control when caring for the person with myeloma. The traditional end-points of clinical trials are disease response, prolongation of disease-free and overall survival, and other objective criteria. However, subjective patient-reported measures, such as symptoms, quality of life, and functional status, are increasingly recognized as important dimensions by which to judge the impact of cancer and its treatment. In multiple myeloma, several patient-reported measures have been used to enrich our understanding of the disease's impact on patients' lives and the risks and benefits of specific treatments.
Immune evasion by CD200: New approaches to targeted therapies for chronic lymphocytic leukemia (CLL)
Authors: A. Kretz-Rommel, N. Dakappagari, F. Qin, J. McWhirter, D. Oltean, E. Ravey, D. Wu, J. Springhorn, A. Saven, K. Bowdish
Journal: Journal of Clinical Oncology (2006)

2519 Background: Although the human immune system is capable of raising an immune response against many cancer types, that response is insufficient to eradicate the cancer in most patients, possibly due to immune evasion through negative regulation of the immune system by the tumor. We identified the immune-suppressive molecule CD200 to be upregulated 1.5–5.4-fold on CLL cells in all 80 patients examined. Interaction of CD200 with its receptor alters cytokine profiles from Th1 to Th2 in mixed lymphocyte reactions, and results in the induction of regulatory T cells, which are thought to hamper tumor-specific effector T cell immunity. We addressed whether CD200 expression on tumor cells plays a role in immune evasion, thereby preventing elimination of tumor cells by the immune system in a xenograft hu/SCID mouse model, and whether treatment with an antagonistic anti-CD200 antibody affects tumor growth. Methods: The human non-Hodgkins lymphoma cell lines RAJI and Namalwa were transduced with human CD200 and injected subcutaneously together with human peripheral blood lymphocytes (PBL) into NOD/SCID mice. Tumor growth over time was compared among mice that either received CD200-expressing tumor cells or received tumor cells lacking CD200 expression. In subsequent experiments, mice were treated with chimeric or humanized anti-CD200 antibodies (doses ranged from 1 to 20 mg/kg) by intravenous injection. Treatment was either started immediately or 7 days after tumor cell injection. Results: As expected, PBLs reduced CD200-negative RAJI or Namalwa tumor growth by up to 75%. In contrast, growth of RAJI or Namalwa tumors expressing CD200 at levels comparable to that of CLL was not reduced by PBLs. Administration of anti-CD200 antibodies at 5 mg/kg resulted in nearly complete tumor growth inhibition (1/10 mice developed a small tumor) over the course of the study even when treatment was started 7 days after tumor cell injection. Conclusions: CD200 expression on tumor cells inhibits the ability of human lymphocytes to eradicate tumor cells. Treatment of CD200-expressing tumors with antagonistic anti-CD200 antibodies inhibits tumor growth, indicating the potential for anti-CD200 therapy as a promising approach for CLL. No significant financial relationships to disclose.
Differentiating the mTOR inhibitors everolimus and sirolimus in the treatment of tuberous sclerosis complex
Authors: Jeffrey P. MacKeigan, Darcy A. Krueger
Journal: Neuro-Oncology (2015)

Tuberous sclerosis complex (TSC) is a genetic autosomal dominant disorder characterized by benign tumor-like lesions, called hamartomas, in multiple organ systems, including the brain, skin, heart, kidneys, and lung. These hamartomas cause a diverse set of clinical problems based on their location and often result in epilepsy, learning difficulties, and behavioral problems. TSC is caused by mutations within the TSC1 or TSC2 genes that inactivate the genes' tumor-suppressive function and drive hamartomatous cell growth. In normal cells, TSC1 and TSC2 integrate growth signals and nutrient inputs to downregulate signaling to mammalian target of rapamycin (mTOR), an evolutionarily conserved serine-threonine kinase that controls cell growth and cell survival. The molecular connection between TSC and mTOR led to the clinical use of allosteric mTOR inhibitors (sirolimus and everolimus) for the treatment of TSC. Everolimus is approved for subependymal giant cell astrocytomas and renal angiomyolipomas in patients with TSC. Sirolimus, though not approved for TSC, has undergone considerable investigation to treat various aspects of the disease. Everolimus and sirolimus selectively inhibit mTOR signaling with similar molecular mechanisms, but with distinct clinical profiles. This review differentiates mTOR inhibitors in TSC while describing the molecular mechanisms, pathogenic mutations, and clinical trial outcomes for managing TSC.
Consent to Biobank Research: Facing Up to the Challenge of Globalization
Authors: Wendy Lipworth, Ian Kerridge
Journal: The American Journal of Bioethics (2015)

Address correspondence to Wendy Lipworth, Senior Research Fellow, Centre for Values, Ethics and the Law in Medicine, Medical Foundation Building (K25), University of Sydney, NSW Australia 2006. E-mail: Wendy.lipworth@sydney.edu.au
EULAR Standing Committee of Investigative Rheumatology: report of activities 2002–3
Authors: C Jorgensen
Journal: Annals of the Rheumatic Diseases (2003)

The Work Group on Gene Therapy in Arthritis presented data in Marseille, 27 February 2003. The group is active, with a high quality of scientific exchange, as the field of gene therapy is changing. One major limitation for the clinical application of gene therapy in joint diseases is the safety of the procedure and the available vectors. The gene therapy trial conducted on 11 SCID children was shortened because of leukaemia induced by the vector. The oncogene activation was shown to be …
The impact of long-term tobacco smoking on circulating IL-16+ NK cells
Authors: Anders Andersson, Apostolos Bossios, Carina Malmhäll, Margareta Sjöstrand, Birgitta Houltz, Ingemar Qvarfordt, Anders Lindén
Journal: European Respiratory Journal (2012)

Natural killer (NK) cells constitute a first line of anti-viral host defence and tobacco smoke may cause reduced cytotoxicity. Among the cytokines expressed in NK cells, interleukin-16 (IL-16) is of interest since it is known that the extracellular concentrations of this CD4 cell chemoattractant are increased in the airways of long-term smokers. Here, we investigated whether long-term smoking alters the number and IL-16 content of circulating NK cells.

Never-smokers (NS) and asymptomatic smokers (AS) with a normal ventilatory capacity plus a normal diffusion capacity for carbon monoxide (DLCO) were included. We also examined smokers with COPD (GOLD stages 2 & 3) with reduced DLCO (>2SD from the predicted mean). In each subject, a peripheral, venous blood sample was taken during clinically stable conditions for flow cytometry analysis of intracellular IL-16 in NK cells (IL-16+ NK cells; IL-16+CD3-CD16+CD56+). The relative and absolute number of NK cells (CD3-CD16+CD56+) was determined.

Smokers (AS and COPD) exhibited a lower relative number of IL-16+ NK cells compared to NS (Mann-Whitney U test, p<0.05). In line with this, the absolute number of IL-16+ NK cells tended to be lower in smokers as well, although this trend was not statistically significant. Among smokers, there was a negative and statistically significant correlation for both the absolute and relative numbers of NK cells, on the one hand, and tobacco load (ie. pack-years; Spearmen Rank Corr. test; p<0.05; rho=-0.056 for both correlations) on the other.

Our study indicates that long-term smoking exerts a negative impact on circulating NK cells, in terms of number and IL-16 content. Hypothetically, this impact may impair anti-viral host-defence.
Suramin and hydrocortisone: determining drug efficacy in androgen-independent prostate cancer.
Authors: W K Kelly, H I Scher, M Mazumdar, D Pfister, T Curley, C Leibertz, L Cohen, V Vlamis, A Dnistrian, M Schwartz
Journal: Journal of Clinical Oncology (1995)

The combination of suramin and hydrocortisone has shown clinical benefit in patients with androgen-independent prostate cancer. Widespread use was limited by the complex dose schedules and the need for pharmacologic monitoring. This study reports three sequential pharmacokinetically derived treatment regimens that simplified the administration of suramin and hydrocortisone with reduced toxicity.Three cohorts of patients with advanced prostate cancer that progressed despite castrate levels of testosterone received oral hydrocortisone plus suramin administered in the following manners: (1) a loading dose of suramin followed by a continuous infusion using an adaptive control program (cohort A); (2) an intermittent schedule using a simplified adaptive control schedule (cohort B); and (3) an empiric dosing regimen (cohort C). Drug concentrations were monitored along with the toxicities associated with each regimen. Efficacy was assessed using measurable-disease criteria, radionuclide scans, and posttherapy changes in prostate-specific antigen (PSA) levels.Fifty-six patients were treated and plasma suramin concentrations were similar for each regimen. A partial response was observed in 4% (one of 28; 95% confidence interval, 0% to 18.4%) of patients with measurable disease, while 12% (six of 50; 95% confidence interval, 4.5% to 24.3%) had a greater than 80% decline in the baseline PSA level. The median duration of response was 12 months. No responses on radionuclide scans were seen. Anemia and lymphocytopenia were the most common toxicities, while 7% of patients developed a sensory or motor neurotoxicity. In the sequential regimens, the frequency of renal insufficiency (P = .04) and coagulopathy (P < .0001) decreased, while transaminase elevations (P = .05) were more common using intermittent infusions (cohorts B and C) versus continuous infusion schedules (cohort A).The administration of suramin was simplified and the drug concentrations were maintained. In this cohort of patients with advanced prostate cancer, the clinical activity of suramin using these dosing schedules was limited. Pharmacodynamic issues, patients selection, and criteria to assess efficacy could have effected the clinical outcome.
Effects of Aggressive Versus Conventional Lipid-Lowering Therapy by Simvastatin on Human Atherosclerotic Lesions
Authors: Roberto Corti, Stephen G. Worthley, Gerard Helft, Juan F. Viles-Gonzalez, Juan J. Badimon, Roberto Corti, Valentin Fuster, Zahi A. Fayad, Stephen G. Worthley, Gerard Helft, William F. Chaplin, Juan F. Viles-Gonzalez, Donald A. Smith, Gabor Mizsei, Juan J. Badimon, Jesse Weinberger, Roberto Corti, Jörg Muntwyler
Journal: Journal of the American College of Cardiology (2005)
Abstract 14753: Geometrical 3D Echocardiographic Reconstruction of the Different Right Ventricular Remodeling in Pulmonary Hypertensive Patients
Authors: Julia Grapsa, David Dawson, Gentaj Jakaj, Luke S Howard, J Simon R Gibbs, Petros Nihoyannopoulos
Journal: Circulation (2011)

Purpose: Using a novel 3D echocardiographic model, we examined the relationship between different right ventricular (RV) remodeling, based on the tricuspid leaflet excursion. Methods: Sixty-two pat...
Subtotal spleen necrosis
Authors: Michael Starck, Wolfgang Koch, Frigga Beitinger, Clemens‐Martin Wendtner
Journal: American Journal of Hematology (2015)

A 73-year-old Caucasian female presented with upper abdominal pain on the left side and exertional dyspnoea. She had a history of indolent B-cell-lymphoma 16 years ago treated with autologous stem cell transplantation. Since then, a “watch and wait” strategy has been taken because of patient preference. At presentation, laboratory findings revealed notable leucocytosis (115,1/nl), anemia (hemoglobin 10,0 g/dl), elevated levels for C-reactive protein (103,8 mg/l, reference < 5 mg/l) and lactate dehydrogenase (1600 U/l). An enlarged spleen with at least 22 cm in diameter was found by abdominal ultrasound. Computed tomography (CT) also showed a massively enlarged spleen with 24 × 20 × 16 cm, a density of 23–45 Hounsfield units and some small spots of air, consistent with the diagnosis of necrotic spleen tissue (Image 1A–C). Because of the risk of splenic rupture and for establishing a conclusive diagnosis, we decided for splenectomy 1. Pathohistologically, an enlarged spleen with a weight of 2770 g was found, tissue was significantly softened with small pseudocystic cavities and extensive necrosis. Microscopically, at the margin area of the necrotic tissue there was a loose infiltration of lymphoid cells, immunohistochemically characterized by expression of CD20 and bcl2, and negative staining for CD10, CD23, bcl6, cycline D1, and DBA44. The proliferation index Ki67 was low (Image 1D–F). The diagnosis of a subtotally necrotic spleen with infiltration of an indolent B-cell-lymphoma was made, consistent with a lymphoplasmacytic lymphoma. Hematologic malignancies such as lymphoma, chronic leukemia, and myelofibrosis are common causes of massive splenomegaly. In addition, storage diseases (e.g. M. Gaucher) and infections (e.g. visceral leishmaniasis) have also to be considered 2. However, an almost complete necrotic transformation of the spleen in the presented case with an indolent lymphoma seems to be unusual. CT scans showed a massively enlarged hypodense spleen with some small spots of air (white arrows). Transversial (A), coronal (B), and sagittal scan (C). On histologic sections, an infiltration with lymphocytes (D, hematoxylin-eosin staining, 400x) with positive staining for CD20 (E, 1000x) and low expression of Ki67 (F, 1000x) was seen. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Ramping Glucosuria for Management of Type 2 Diabetes Mellitus: An Emerging Cynosure
Authors: Priyanka Malla, Rajnish Kumar, Manoj K. Mahapatra, Manoj Kumar
Journal: Medicinal Research Reviews (2014)

Abstract Chronic hyperglycemia is a characteristic feature of type 2 diabetes mellitus (T2DM). The kidney plays a vital role in maintaining blood glucose homeostasis by recovering glucose from glomerular filtrate which is controlled by SGLT2 cotransporters expressed mainly in proximal tubule. In T2DM patients, inhibition of SGLT2 normalizes glycemic levels by preventing glucose from being reabsorbed through SGLT2 and re‐entering the circulation. Thus, SGLT2 inhibition seems to be a logical approach and pose a novel insulin‐independent mechanism of action for management of T2DM by promoting urinary glucose excretion in the body. Canagliflozin is the first SGLT2 inhibitor approved by US Food and Drug Administration (US FDA) followed by dapagliflozin while empagliflozin is under FDA review. Various other drug candidates in late‐stage clinical developments are also expected to hit the global markets in the coming years. In this review, studies on various early‐ and late‐stage SGLT2 inhibitors have been investigated and recent clinical developments summarized.
Abstract 101: Gender Differences in the Timing of Access to the Prehospital Phase of STEMI Care
Authors: Robert O’Connor, Ross Megargel, Angela DiSabatino, William Weintrub, Charles Reese
Journal: Circulation (2007)

Introduction : The purpose of this study is to determine the degree of gender differences in lay person recognition, emergency medical services (EMS) activation, and the prehospital management of STEMI. Methods : Data were gathered prospectively from May 1999 to January 2007 on consecutive patients with STEMI who presented to a tertiary care hospital emergency department. Patients arriving by ambulance and private vehicle were included. Data collection included determining symptom duration, whether a prehospital ECG was obtained, whether the cardiac interventional lab was activated prior to patient arrival at the hospital, patient age, and hospital length of stay. Prehospital activation of the cath lab was done by emergency medicine based on paramedic ECG interpretation in consultation with cardiology. Statistical analysis was performed using the Mann-Whitney U test, the Yates-corrected chi-square test, and linear regression. Results : A total of 3260 cases were studied, of which, 3097 had complete data for analysis. Only EMS cases were included in the ECG analysis, and only patients having a prehospital ECG were included in the prehospital activation of cath lab analysis. Regression analysis showed that older age and female gender were significant predictors of access and arrival by EMS. The mean age in years was higher for EMS arrival (69 women; 59 men) than for private vehicle (62 women; 56 men). Conclusion : Women with STEMI tend to use EMS more frequently then men, but are older and wait longer before seeking treatment. Whether these factors contribute to the longer length of stay remains to be determined.
Interaction of thymic stromal lymphopoietin, <scp>IL</scp>‐33, and their receptors in epithelial cells in eosinophilic chronic rhinosinusitis with nasal polyps
Authors: B. Liao, P.‐P. Cao, M. Zeng, Z. Zhen, H. Wang, Y.‐N. Zhang, C.‐Y. Hu, J. Ma, Z.‐Y. Li, J. Song, J.‐X. Liu, L.‐Y. Peng, Y. Liu, Q. Ning, Z. Liu
Journal: Allergy (2015)

Abstract Background Thymic stromal lymphopoietin ( TSLP ), IL ‐25, and IL ‐33 system contribute to the initiation and development of Th2 responses. This study aimed to explore the involvement of TSLP , IL ‐25, IL ‐33, and their receptors in type 2 T‐helper (Th) responses in chronic rhinosinusitis with nasal polyps ( CRS w NP s) and their cross‐regulation in human nasal epithelial cells ( HNEC s). Methods Immunohistochemistry, quantitative RT ‐ PCR , ELISA , Bio‐Plex assay, and flow cytometry were used to detect the expression of TSLP /common γ‐like TSLP receptor ( TSLPR )/ IL ‐7 receptor α ( IL ‐7Rα), IL ‐25/ IL ‐17B receptor ( IL ‐17 RB ), and IL ‐33/membrane‐bound ST 2 ( ST 2L)/soluble ST 2 ( sST 2) in sinonasal mucosa and HNEC s. HNEC s cultured at an air–liquid interface were used to explore the expression in regulation of these cytokine systems. Results Compared with controls and noneosinophilic CRS w NP , the expression of TSLP / TSLPR / IL ‐7Rα and ST 2L/ sST 2 was significantly increased in eosinophilic CRS w NP , predominantly in epithelial cells. In contrast, the expression of IL ‐33 and IL ‐25/ IL ‐17 RB was enhanced in epithelial cells in both eosinophilic and noneosinophilic CRS w NP compared to controls. The expression of TSLP , TSLPR , and ST 2L was positively correlated with symptom and computer tomography scan scores in eosinophilic CRS w NP and with Th2 cytokine expression in sinonasal mucosa. The expression of ST 2L was correlated with TSLP and its receptor expression. TSLP could induce ST 2L expression that promoted IL ‐33‐induced TSLP expression in HNEC s. In addition, TSLP / TSLPR / IL ‐7Rα and ST 2L could be induced by Th2 cytokines, while IL ‐25/ IL ‐17 RB and IL ‐33 could be upregulated by Th1/Th17 cytokines, in HNEC s. Conclusions The positive feedback loop between TSLP , IL ‐33 and their receptors, and Th2 cytokines may facilitate Th2‐skewed inflammation in eosinophilic CRS w NP .
Infiltrating ductal carcinoma of the breast: the survival impact of race.
Authors: M J Edwards, J W Gamel, W P Vaughan, W R Wrightson
Journal: Journal of Clinical Oncology (1998)

Breast cancer has a poorer prognosis among black women than among white women. This review was conducted to determine whether this disparity reflects the direct impact of race on likelihood of cure or on time to death from breast cancer or stems from the interaction of race with tumor stage and patient age.We analyzed data from 115,838 patients with localized (node-negative) and regionally metastatic (node-positive) breast cancer from the Surveillance, Epidemiology, and End-Results (SEER) Program of the National Cancer Institute. Parametric analysis was used to determine the independent prognostic value of age, stage, and race. Linear regression and distribution analyses were also used to examine the interaction of these covariates.The prevalence of regionally metastatic disease, relative to localized disease, declined with increased age among white patients and those classified as "other," but remained relatively constant among black patients. Parametric analysis showed a smaller cured fraction and shorter time to death when patients with regional disease were compared with those with localized disease. A similar disparity was found when black patients were compared with those classified as white or other.Age and race have a significant association with tumor stage. In addition, our data show that race has an independent impact on the clinical course of breast cancer and diminishes both the likelihood of cure and time to death among uncured patients.