tbuckley/cabot-search huggingface dataset:
Phase Ia/Ib trial of bispecific antibody MDX-210 in patients with advanced breast or ovarian cancer that overexpresses the proto-oncogene HER-2/neu.
Authors: F H Valone, P A Kaufman, P M Guyre, L D Lewis, V Memoli, Y Deo, R Graziano, J L Fisher, L Meyer, M Mrozek-Orlowski
Journal: Journal of Clinical Oncology (1995)

MDX-210 is a bispecific antibody that binds simultaneously to type I Fc receptors for immunoglobulin G (IgG) (Fc gamma RI) and to the HER-2/neu oncogene protein product. MDX-210 effectively directs Fc gamma RI-positive effector cells such as monocytes and macrophages to phagocytose or kill tumor cells that overexpress HER-2/neu. The goals of this phase Ia/Ib trial were to determine the maximum-tolerated dose (MTD) and/or the optimal biologic dose (OBD) of MDX-210.Patients with advanced breast or ovarian cancer that overexpressed HER-2/neu were eligible for treatment. Cohorts of three patients received a single intravenous (IV) infusion of MDX-210 at increasing dose levels from 0.35 to 10.0 mg/m2.Treatment was well tolerated, with most patients experiencing transient grade 1 to 2 fevers, malaise, and hypotension only. Two patients experienced transient grade 3 hypotension at 10.0 mg/m2. Transient monocytopenia and lymphopenia developed at 1 to 2 hours, but no other hematologic changes were observed. Doses of MDX-210 > or = 3.5 mg/m2 saturated > or = 80% of monocyte Fc gamma RI and produced peak plasma concentrations > or = 1 microgram/mL, which is greater than the concentration for optimal monocyte/macrophage activation in vitro. Elevated plasma levels of the monocyte products tumor necrosis factor alpha (TNF alpha), interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), and neopterin were observed with maximal levels at doses > or = 7.0 mg/m2. Localization of MDX-210 in tumor tissue was demonstrated in two patients. One partial and one mixed tumor response were observed among 10 assessable patients.MDX-210 is immunologically active at well-tolerated doses. The MTD and OBD is 7 to 10 mg/m2.
Limits of normality of quantitative thoracic CT analysis
Authors: Massimo Cressoni, Davide Chiumello, Eleonora Carlesso, Elisabetta Gallazzi, Antonella Marino, Matteo Brioni, Chiara Chiurazzi, Federica Ylenia Romano, Daniela Febres, Luciano Gattinoni
Journal: European Respiratory Journal (2011)

Introduction:  Quantitative CT scan analysis has been widely studied in ARDS patients, while, data on healthy population are scanty. Reference values, however, would be of clinical relevance when assessing, i.e., the excess lung weight or edema, or whatever change in CT anatomy/physiology induced by disease.   Methods:  We retrospectively included patients who underwent a spiral CT scan for clinical reasons and whose images were considered normal by radiologists. Lungs were outlined on each CT image with a dedicated software; lung weight, volume and tissue fraction were computed with a dedicated software.   Results:  We enrolled 52 patients (25 males), age 65±12 years, height 1.67±0.09 m, BMI 26±4 kg/m 2 . The table summarizes the main CT scan characteristics of patients, with CT taken at near total lung capacity.  While the gas values are dependent on inflation, the lung weight is not. Therefore, of particular note the significant correlation between height and total lung weight (p 2 =0.40) according to the equation: total lung weight = –1268 + height$*$1311. The correlation between height and total lung volume is statistically significant (p 2 =0.51) according to the equation: total lung volume = –15250 + height$*$12001.   Conclusions:  Lung weight and volume are related to height in a healthy population.
Estimated short-term effects of air pollutants on daily respiratory emergency department visits in three Swedish cities
Authors: Kadri Meister, Bertil Forsberg
Journal: European Respiratory Journal (2012)

Large number of epidemiological studies has found associations between daily changes in ambient particulate air pollution and different kinds of health outcomes. Our aim was to estimate the short-term effects of different air pollutants on daily emergency department visits for respiratory diagnoses in three largest cities in Sweden to find the effects in different environments. Data on daily number of visits from 2001 through 2008 in Stockholm, Gothenburg and Malmo were collected from the national Patient Register and data on daily air pollution concentrations (PM 10 , NOx and Ozone and when available, PM 2.5 ) from the local environmental agencies. In addition to visits for all respiratory causes focus was on visits for asthma (ICD10: J45-J46) and on associations between air pollution and daily visits in different age classes. Data was analysed using additative Poisson regression models to examine the association between daily visits and the average levels of air pollutants on the day of visit and the day before (lag01). For each city a statistical model was constructed for each health outcome and also for each age class. For example, a Stockholm model adjusted for the time trend, temperature, relative humidity, birch pollen levels, day of week and public holidays gives an increase of 2% (95 % CI 0.5 to 3.6%) in daily visits for asthma for all ages per 10 µg/m3 increase in PM 10 . The estimated effect for children is 2.5% (95 % CI 0.7 to 4.4%) and for elderly 4.9% (95 % CI 1.1 to 8.8%), respectively. In this study we have found associations between relatively low daily levels of air pollutants and emergency department visits for respiratory diagnoses.
Single-breath diffusion: Comparison between helium and methane as tracer gases in COPD and healthy controls
Authors: Rachel Salvador-Ong, Erica Dijkers, Reindert Steenwijk van, Peter Sterk
Journal: European Respiratory Journal (2014)

Rationale:  A real-time gas analyzer for methane (CH4 ) has been introduced as alternative for helium (He) in determining the alveolar volume (VA) for the single-breath diffusing capacity for carbon monoxide (DLCO). A difference can be expected due to the physical properties of these gases. Since the clinical relevance of changing tracer gases in single-breath diffusion has not been published, an adequate comparison is warranted.   Objective:  The aim of this study was to compare the DLCO and VA obtained using He and CH4 among COPD patients and healthy controls in order to examine whether their results are equivalent.   Methods:  This prospective, cross-over study included 10 healthy controls and 10 COPD patients. The DLCO and VA were measured in random order and in accordance to ATS/ERS guidelines. The correlations between the results were calculated using intraclass correlation test and visualized with Bland and Altman.   Results:  The intraclass correlation coefficient for the DLCO and VA was both 0.99 for the total group and in separating the groups the same intraclass correlation was found. The Bland and Altman analysis of DLCO and VA results from COPD patients showed a difference of -0.08 mmol/min/kPa (limits of agreement (LOA) -0.63 - 0.47) and -0.09 liter (LOA -0.33 - 0.15) respectively; for the healthy control the difference is 0.36 mmol/min/kPa (LOA -0.47 - 1.19) for DLCO and -0.03 liter (LOA -0.39 - 0.32) for VA.   Conclusion:  The DLCO and VA results obtained by CH4 as tracer gas correspond to those by He both among COPD patients and healthy controls. This suggests that CO diffusion capacity obtained by CH4 can be used for follow-up from previous tests obtained with He.
Pre-emptive oral ganciclovir can reduce the risk of cytomegalovirus disease in liver transplant recipients
Authors: J. Torre-Cisneros, J.A. Madueño, C. Herrero, M. de la Mata, R. Gonzalez, A. Rivero, G. Miño, P. Sánchez-Guijo
Journal: Clinical Microbiology and Infection (2002)
The effects of swimming training on alterations in structure and function of sternohyoid muscle of model rats of metabolic syndrome
Authors: Liqiang Zhang, Xiaorui Bi, Wanzhen Yao, Jiandong Wang, Bei He
Journal: European Respiratory Journal (2012)

We investigated the effects of swimming training on alterations in structure and function of sternohyoid muscle in model rats of metabolic syndrome. Male Sprague-Dawley rats were randomly divided into 3 groups: control group(group A), MS group(group B), swimming training MS group(group C). The level of malondialdehy of sternohyoid muscles in group B was significantly higher than those of group A and group C.The Superoxide dismutase level of sternohyoid muscles in group B was significantly lower than those of group A and group C. The capillary density, capillary-to-fiber ratio(C/F), cross-sectional area of type I and II fiber, percentage of type I fibers of the isolated sternohyoid muscles in group B were significantly lower than those of group A and group C. In group B, mitochondrions were swelling, vacuolization and reduced, myofibril was dissolved focally. In group C, mternohyoid myofibril was arranged normally, ultrastructure of mitochondrion was normal roughly, occasionally vacuolization. The tensions of sternohyoid muscle of group B were significantly lower than those of group A and group C. In fatigue test, the tension percentages of sternohyoid muscle of group B were significantly lower than those of group A and group C. We concluded that the abnormalities in histological structure and ultrastructure of upper airway muscle induced by MS, via oxidative stress, led to reduction in contractile function in upper airway muscles, contributing to sleep apnea, and swimming training improved contractile dysfunction of upper airway muscles by inhibiting oxidative stress in MS.
Tumor-Induced Skin Heterogenization. II. Virus Causing the Phenomenon
Authors: George J. Svet-Moldavsky, Alexander L. Liozner, Demuri M. Mkheidze, Pavel P. Sokolov, Albert P. Bykovsky
Journal: JNCI Journal of the National Cancer Institute (1970)

Journal Article Tumor-Induced Skin Heterogenization. II. Virus Causing the Phenomenon Get access George J. Svet-Moldavsky, M.D., George J. Svet-Moldavsky, M.D. Laboratory of Virology, Institute of Experimental and Clinical Oncology, Moscow, USSR Search for other works by this author on: Oxford Academic PubMed Google Scholar Alexander L. Liozner, Alexander L. Liozner Laboratory of Virology, Institute of Experimental and Clinical Oncology, Moscow, USSR Search for other works by this author on: Oxford Academic PubMed Google Scholar Demuri M. Mkheidze, Demuri M. Mkheidze Laboratory of Virology, Institute of Experimental and Clinical Oncology, Moscow, USSR Search for other works by this author on: Oxford Academic PubMed Google Scholar Pavel P. Sokolov, Pavel P. Sokolov Laboratory of Virology, Institute of Experimental and Clinical Oncology, Moscow, USSR Search for other works by this author on: Oxford Academic PubMed Google Scholar Albert P. Bykovsky, M.D. Albert P. Bykovsky, M.D. Laboratory of Virology, Institute of Experimental and Clinical Oncology, Moscow, USSR Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 45, Issue 3, September 1970, Pages 475–484, https://doi.org/10.1093/jnci/45.3.475 Published: 01 September 1970 Article history Received: 10 February 1970 Accepted: 06 May 1970 Published: 01 September 1970
Phase I-II study of irinotecan hydrochloride combined with cisplatin in patients with advanced gastric cancer.
Authors: K Shirao, Y Shimada, H Kondo, D Saito, T Yamao, H Ono, T Yokoyama, H Fukuda, M Oka, Y Watanabe, A Ohtsu, N Boku, T Fujii, Y Oda, K Muro, S Yoshida
Journal: Journal of Clinical Oncology (1997)

PURPOSE A dose-escalation study of irinotecan hydrochloride (CPT-11) combined with fixed-dose cisplatin was conducted to determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and objective response rate in patients with advanced gastric cancer. PATIENTS AND METHODS Twenty-four patients with or without prior chemotherapy were enrolled. All patients were assessable for toxicities and response. On day 1, CPT-11 was administered as a 90-minute intravenous (I.V.) infusion, which was followed 2 hours later by a 120-minute I.V. infusion of cisplatin 80 mg/m2. CPT-11 alone at the same dose was administered again on day 15. The treatment was repeated every 4 weeks until disease progression was observed. The initial dose of CPT-11 was 60 mg/m2, and was escalated in increments of 10 mg/m2 until severe or life-threatening toxicity was observed. RESULTS The MTD of this combination was CPT-11 80 mg/m2. At this dose level, 16.7% of patients (two of 12) had leukopenia of less than 1,000/microL, 66.7% (eight of 12) had neutropenia of less than 500/microL, and 16.7% (two of 12) had severe diarrhea of grade 4 during the first course. The dose-limiting toxicity was neutropenia. Ten patients achieved a partial response (PR), and the overall response rate was 41.7% among 24 patients (95% confidence interval, 21.9% to 61.4%). CONCLUSION The recommended dose and schedule is CPT-11 70 mg/m2 on days 1 and 15 and cisplatin 80 mg/m2 on day 1 every 4 weeks. This combination of CPT-11 and cisplatin, considered to be active against advanced gastric cancer with acceptable toxicity, should be further assessed in a phase II study.
High-Dose Melphalan, Etoposide, Total-Body Irradiation, and Autologous Stem-Cell Reconstitution as Consolidation Therapy for High-Risk Ewing’s Sarcoma Does Not Improve Prognosis
Authors: Paul A. Meyers, Mark D. Krailo, Marc Ladanyi, Ka-Wah Chan, Scott L. Sailer, Paul S. Dickman, David L. Baker, Jeffrey H. Davis, Robert B. Gerbing, Alfred Grovas, Cynthia E. Herzog, Karen L. Lindsley, Wen Liu-Mares, James B. Nachman, Lance Sieger, Jean Wadman, Richard G. Gorlick
Journal: Journal of Clinical Oncology (2001)

To determine whether consolidation therapy with high-dose melphalan, etoposide, and total-body irradiation (TBI) with autologous stem-cell support would improve the prognosis for patients with newly diagnosed metastatic Ewing's sarcoma (ES).Thirty-two eligible patients with newly diagnosed ES metastatic to bone and/or bone marrow were enrolled onto this study. Treatment was initially comprised of five cycles of induction chemotherapy (cyclophosphamide, doxorubicin, and vincristine alternating with ifosfamide and etoposide) and local control. Peripheral-blood stem-cell collection was performed after the second cycle of chemotherapy, with delay if the bone marrow was persistently involved. If patients had a good response to initial therapy, they proceeded to consolidation therapy with melphalan, etoposide, TBI, and stem-cell support.Of the 32 eligible patients, 23 proceeded to high-dose therapy consolidation. Of the nine patients who did not proceed to consolidation, four were secondary to progressive disease and two were secondary to toxicity. Three patients died from toxicity during the high-dose phase of the therapy. The majority of the patients who underwent high-dose consolidation therapy experienced relapse and died with progressive disease. Two-year event-free survival (EFS) for all eligible patients is 20%. The 2-year post-stem-cell reconstitution EFS for the subset of 23 patients who received consolidation therapy is 24%. Analysis of peripheral-blood stem-cell collections by molecular techniques for minimal residual disease showed contamination of at least some samples by tumor cells in all three patients with available data.Consolidation with high-dose melphalan, etoposide, TBI, and autologous stem-cell support failed to improve the probability of EFS in this cohort of patients with newly diagnosed metastatic ES.
High incidence of the Beijing strains among multi drug resistance isolates of Mycobacterium tuberculosis from extra pulmonary tuberculosis cases in northern India
Authors: Anand Kumar Maurya, Surya Kant, Vijaya Lakshmi Nag, Ram Awadh Singh Kushwaha, Tapan N. Dhole
Journal: European Respiratory Journal (2012)

Background: The emergence and spread of drug resistance tuberculosis has worsened the global resurgence of tuberculosis. Beijing strains are responsible for massive spread and outbreaks of Multidrug resistance Mycobacterium tuberculosis (MDR-TB) in worldwide as well as in India.

Objectives: The aim of study presented here was to investigate incidence of Beijing genotypic among MDR-TB isolates from extra pulmonary tuberculosis cases (EPTB) in Northern India.

Methods: A total of 756 specimens from patients of EPTB cases with varied presentation were studied. A total of 164 M. tuberculosis complex (MTBC) isolates recovered during the period Sept 2007-Dec 2010 were tested for drug susceptibility against SHRE by radiometric BACTEC method. MDR-TB isolates were sequenced in rpoB and katG gene for mutation analysis. All MDR-TB strains were processed by new multiplex polymerase chain reaction (PCR) for identification of Beijing strains and non Beijing strains.

Results: Of these 164 MTBC, 100(60.9%) strains were fully susceptible and 64(39.1%) strains were resistance. 21 (12.8%) strains were confirmed MDR-TB by genotypic method. The proportional of Beijing strains was significantly higher among MDR-TB strains (72.7%, p < 0.05). Genotypic analysis of rpoB gene revealed significantly higher rate of Ser531Leu mutation rate among Beijing vs. non Beijing strains (50% vs. 33.4%, p < 0.05). While mutation for Ser315Thr in katG gene was common among Beijing vs. non Beijing strains (68.2% vs. 50%, p < 0.05).

Conclusion: We found high incidence of Beijing strains among MDR-TB strains from EPTB cases in Northern India.
Differential roles of Toll-like receptors in the elicitation of proinflammatory responses by macrophages
Authors: B W Jones, K A Heldwein, T K Means, J J Saukkonen, M J Fenton
Journal: Annals of the Rheumatic Diseases (2001)

BACKGROUND Mammalian Toll-like receptor (TLR) proteins are pattern recognition receptors for a diverse array of bacterial and viral products. Gram negative bacterial lipopolysaccharide (LPS) activates cells through TLR4, whereas the mycobacterial cell wall glycolipids, lipoarabinomannan (LAM) and mannosylated phosphatidylinositol (PIM), activate cells through TLR2. Furthermore, short term culture filtrates of M tuberculosis bacilli contain a TLR2 agonist activity, termed soluble tuberculosis factor (STF), that appears to be PIM. It was recently shown that stimulation of RAW264.7 murine macrophages by LPS, LAM, STF, and PIM rapidly activated NF-κB, AP1, and MAP kinases. RESULTS This study shows that signalling by TLR2 and TLR4 also activates the protein kinase Akt, a downstream target of phosphatidylinositol-3′-kinase (PI-3-K). This finding suggests that activation of PI-3-K represents an additional signalling pathway induced by engagement of TLR2 and TLR4. Subsequently, the functional responses induced by the different TLR agonists were compared. LPS, the mycobacterial glycolipids, and the OspC lipoprotein (a TLR2 agonist) all induced macrophages to secrete tumour necrosis factor α (TNFα), whereas only LPS could induce nitric oxide (NO) secretion. Human alveolar macrophages also exhibited a distinct pattern of cellular response after stimulation with TLR2 and TLR4 agonists. Specifically, LPS induced TNFα, MIP-1β, and RANTES production in these cells, whereas the TLR2 agonists induced only MIP-1β production. CONCLUSION Together, these data show that different TLR proteins mediate the activation of distinct cellular responses, despite their shared ability to activate NF-κB, AP1, MAP kinases, and PI-3-K.
Is motivational Q-mat test useful to predict smoking cessation?
Authors: Zahra Hessami, Hooman Sharifi, Gholamreza Heydari, Mohammadreza Masjedi
Journal: European Respiratory Journal (2012)

Background : Smoking is one of the major causes of cancer, heart and pulmonary diseases. one of essential steps in tobacco control is persuading the smokers to quit smoking. Encouraging smokers to the quit can be possible if the smoker has enough motivation for quit. In this study we investigated abstinence rate after 6 months according to level of motivation to quit (Q-mat score) and level of nicotine dependency (Fagerestrom score).   Material and Method:    This study was conducted on the volunteers of smoking cessation clinic in Tehran.They underwent tests for nicotine dependence, motivation degree assessment by FT and Q-mat test respectively. Thereafter, smokers started the cessation program consisting in behavioral therapy and pharmacotherapy. Their quit rate was by verified by telephone and through exhaled co measurement after 6 months.   Results:   In this study 345 volunteers were studied from which 311 (90.1%) male. The mean age was 37.6±11.04 years. After 6 months fallow up abstinence rate was 39%. The mean of Q-mat score was 15.8±5.1 (14.9-16.7 CI 95%) in participants how stopped smoking and 15.4±5.1 (14.7-16.1CI 95%) among participants who failed smoking cessation (p=0.4). The mean of FT was 5.2±2.6 (4.7-5.6 CI 95%) in participants who stopped smoking and was 6±2.6 (5.7-6.4 CI 95%) among participants failed (p=0.002).   Conclusion:    The results of this study indicate that volunteers may have high motivation to quit smoking however there was not correlation with the quit rate after 6 months. Lower fagerestrom score is correlated with high quit rate. By contrast, Q-mat score didn9t predict the success rate in the observed population. Thus in this regards attention should be paid on high nicotine dependent smokers.
A role for ST2/IL-33 signalling in fibroblast proliferation utilising a novel transgenic mouse model of pulmonary hypertension
Authors: Colin Church, Ammad Mahmood, Charlie McSharry, Damo Xu, Andrew Peacock, David Welsh
Journal: European Respiratory Journal (2011)

In this study, we determined if the ST2 receptor and its ligand, interleukin-33 (IL-33) was involved in mouse PAF proliferation and if ST2-/- mice displayed a pulmonary hypertensive phenotype (RVH).  Wild type (WT) and ST2 knockout mice (ST2-/-) were used. The effect of IL-33 on proliferation of WT cells was determined by incubation in hypoxia (35mmHg). p38 MAPK, which is involved in fibroblast proliferation, was detected by Western blotting. Right ventricular hypertrophy (RVH) was assessed by measuring the right ventricular wall (RV) and left ventricle with the septum (LV+S).  ST2-/- cells proliferated to a greater level compared to WT cells (p  p38 MAPK was detected in ST2-/- cells but not in WT cells. Proliferation to hypoxia in WT cells could be blocked by IL-33. The ST2-/- mice displayed right ventricular hypertrophy (Fig. 2, p  Excessive proliferation of fibroblasts from ST2-/- mice involves p38 MAPK. Proliferation by hypoxia in WT cells can be blocked by IL-33. ST2-/- mice display a pulmonary hypertensive phenotype.
Prevalence trends in Sweden for the new variant of Chlamydia trachomatis
Authors: M. Klint, R. Hadad, L. Christerson, B. Loré, C. Anagrius, A. Österlund, I. Larsson, S. Sylvan, H. Fredlund, M. Unemo, B. Herrmann
Journal: Clinical Microbiology and Infection (2010)