tbuckley/cabot-search huggingface dataset:
X-Ray Responses of Human Colon Tumor Cells Grown in Artificial Capillary Culture&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Masanori Nakazawa, John T. Leith, Arvin S. Glicksman
Journal: JNCI Journal of the National Cancer Institute (1984)

Clone A human colon adenocarcinoma cells were grown in three-dimensional artificial capillary culture (ACC) to determine responses of capillaries treated 3 weeks after tumor cell inoculation with a specific, easily quantifiable cytotoxic agent, ionizing radiation. The high-density growth of tumor cells in ACC can be considered to be an in vitro analogue of a solid tumor. Changes in extracapillary space (ECS) fluid concentrations of lactate dehydrogenase (LDH) and aspartate aminotransferase (GOT) and the utilization of glucose in circulating medium were monitored after a supralethal radiation dose (90 Gy) of X-rays. Immediately after irradiation, increased levels of LDH and GOT were found that reached maximum levels about four to five times those found in nonirradiated control capillaries at 10-13 days post irradiation and then declined. Patterns of enzyme production appeared to correlate with the numbers of nonviable tumor cells collected from the ECS of the artificial capillaries. In contrast, glucose utilization showed little correlation with either enzyme concentration or dead cell production. It was determined that, while capillaries grown and treated in this manner appear to respond in a dose-dependent manner to ionizing radiation (as indicated by changes in LDH and GOT levels), these particular end points are relatively insensitive and are not suitable for studies in which therapeutic levels of X-radiation might be given. In other studies, tumor cells were removed from unirradiated capillaries by trypsinization and used to obtain complete survival curves after graded doses of X-radiation. The dose-response curves obtained indicate that clone A colon tumor cells grown in ACC show a marked decrease in their ability to accumulate sublethal radiation injury as compared to responses of these cells growing exponentially in asynchronous monolayer cultures, to synchronized mid-G1 tumor cells, or to tumor cells in stationary growth phase. These data suggest that ACC is a potentially useful model to study the effects of cytotoxic agents on human tumor cells.
Is pneumonia in elderly an enigma: A study from a multispecialty hospital in rural India
Authors: B.N.B. Mahaveera Prasad, C.A. Tukaram
Journal: European Respiratory Journal (2011)

Aim:  To study the manifestations and outcome of pneumonia in elderly from a rural background in India.   Methods:  Retrospective analysis of clinical, radiological and laboratory features and treatment outcome of severe community-acquired pneumonia among eldely who were managed in a multispecialty hospital in rural India during preceding 2 years.   Results:  28 cases in this study included 22 males and 6 females in the age group of 72 to 88 years. 16 cases had comorbidities- COPD in 8, diabetes in 5 and chronic liver disease in 3. Etiology included streptococcus pneumoniae in 11, staphylococcus aureus in 5, H. influenzae in 3 and klebsiella pneumoniae in 2 cases. In 7 cases definitive organism could not be isolated. Only 6 had typical features of fever, chest pain, cough, pulmonary consolidation and neutrophil leucocytosis. Extrapulmonary features misleading initial diagnosis were predominant in the remaining cases. All of them had altered mental status and profound general weakness with minimal and non specific chest findings. 4 had pain abdomen and loose motions as presenting features. Among cases with atypical presentation 8 had leucopenia while the remaining had neutrophil leucocytosis.18 cases required hospitalisation of more than 3 weeks and only 14 responded to therapy.Pneumococcal-fluoroquinolone resisance was observed in 2 cases.16 cases required mechanical ventilation and among them only 2 survived. Ventilatory associated lung injury was present in 3 cases. Non responders had severe sepsis with ARDS and multiorgan failure.   Conclusion:  Pneumonia in elderly is an enigma, often caused by common pathogens and is associated with atypical features, complicated course and poor treatment outcome.
Review of applications of fluorescence excitation spectroscopy to dermatology
Authors: W. Franco, E. Gutierrez-Herrera, N. Kollias, A. Doukas
Journal: British Journal of Dermatology (2015)

Summary Endogenous molecules that exhibit fluorescence hold the potential to serve as reporters of tissue structure, activity and physiology. Fluorescence excitation spectroscopy is one means to measure and express tissue's innate fluorescence. This review focuses on the application of endogenous fluorescence ultraviolet excitation spectroscopy to dermatology.
Pearl's PT010 triple combination provides comparable budesonide exposure to symbicort and comparable glycopyrronium and formoterol exposure to PT003
Authors: Colin Reisner, Carlos Fernandez, Patrick Darken, Paolo DePetrillo, Earl St. Rose, Tracy Fischer, Shannon Strom, Michael Kong, Kar Wong, Shahid Siddiqui, Greg Tardie, Chadwick Orevillo
Journal: European Respiratory Journal (2014)

Introduction:  To our knowledge, no fixed-dose triple combination has been formulated without a drug-drug interaction (DDI). Budesonide (BD), glycopyrronium (GP), and formoterol fumarate (FF) MDI (BGF MDI, PT010) is a fixed-dose ICS/LAMA/LABA in Pearl Therapeutics9 co-suspension technology in development for COPD. The objectives of this study were to identify a dose of BD in BGF MDI that provides comparable PK to BD following administration of Symbicort ®  MDI 320/9µg and assess whether a DDI exists, comparing PK of GFF MDI (PT003) to BGF MDI.   Methods:  This Phase I, randomized, double-blind within device, single-dose, crossover study randomized 84 healthy subjects to BGF MDI 320/14.4/9.6μg, GFF MDI 14.4/9.6μg and Symbicort MDI 320/9μg, and either: BGF MDI 160/14.4/9.6μg, BGF MDI 80/14.4/9.6μg or Symbicort MDI 160/9μg. PK parameters were derived from plasma concentration-time data.   Results:  Bioequivalence (BE) was achieved for all relevant comparisons.  Similar observations were made for lower dose comparisons.   Conclusion:  No DDI was evident when comparing PK of BGF MDI to GFF MDI. Systemic exposure to BD following administration of BGF MDI 320/14.4/9.6μg was slightly higher but BE to Symbicort MDI 320/9μg.
The oncogene c-Src plays a crucial role in the pathogenesis of COPD
Authors: Patrick Geraghty, Andrew Hardigan, Robert Foronjy
Journal: European Respiratory Journal (2013)

Activation of the tyrosine kinase c-Src promotes tumor invasion, loss of cell-cell adhesion, increased cell-matrix adhesion, and formation of focal adhesions. Cigarette smoke is known to activate c-Src kinase in a cancer phenotype, however little is known about the activation status of c-Src in non-cancerous lung diseases such as emphysema. The objective of this study was to examine whether c-Src is cigarette smoke activated and contributes to COPD progression. Increased c-Src activity was observed in small airway epithelial (SAE) cells and mouse lungs exposed to smoke and in advanced human emphysema lungs (Gold 3 or greater) compared to age matched control lungs. Cigarette smoke activated raf-1, ERK, JNK and p38 in a c-Src dependent manner in both SAE cells and mouse lung. Given these observed effects, A/J mice were orally administered the specific Src inhibitor AZD0530 while they were exposed to 2 months of cigarette smoke. Treatment with AZD0530 blocked c-Src activation and prevented the smoke-mediated influx of macrophages in the lung. In addition, inhibiting Src in these mice countered Raf, ERK, JNK, p38 activation, blocked the induction of MMP-9 and IL-17 and prevented the development of air space enlargement in the lung. Furthermore, it was determined that cigarette smoke directly triggers Src to phosphorylate EGFR and thereby activate MAPK pathways that have been implicated in the disease pathogenesis. Together, these results indicate that inhibition of c-Src activity represents a novel approach to prevent cigarette smoke induced inflammation and injury.
Quality of life, oxygen desaturation and dyspnea during ADL in non-hypoxemic patients grouped according symptoms by combined COPD assessment
Authors: Marina Sallum Barusso, Júlia Gianjoppe-Santos, Renata P. Basso-Vanelli, Eloisa M.G. Regueiro, Jéssica C. Panin, Valéria A. Pires Di Lorenzo
Journal: European Respiratory Journal (2014)

Background:  The GOLD 2011 update recommends that the management and treatment of COPD should combine the impact of disease and future risk of exacerbations. Patients with COPD have poor quality of life (QoL) and may have limitation in their activities of daily living (ADL), which could be manifested as oxygen dessaturation (OD) and progressive dyspnea.  Aim:  To verify whether the most symptomatic patients have higher ADL limitations and impaired QoL compared with those less symptomatic.  Methods:  In a cross-sectional study and 44 non-hypoxemic patients with COPD (FEV 1  49±15%pred, SpO2≥90%, 69±8yrs) were categorized by GOLD and grouped by symptoms in B/D (n=19) and A/C (n=25). The modified Medical Research Council (mMRC), the London Chest Activity Daily Living (LCADL) scales and the Saint George9s Respiratory Questionnaire (SRGQ) were applied. In addition, an ADL simulation in appropriate laboratory was conducted.  Results:  There are no association between the patients9 symptoms and OD and dyspnea (X² test); however it was observed a higher prevalence of OD in B/D. In both groups there were patients who had any reports of dyspnea while performing the ADL. No correlation was found between dyspnea and OD variation. The B/D showed higher ADL dyspnea (LCADL %total =30%; p total =46%; p Conclusion:  The combined COPD assessment was not efficient to determining the OD and dyspnea while performing ADL; however the symptoms is a factor that interfere in ADL and QoL, whereas more symptomatic patients had poorly QoL and greater reported dyspnea in ADL.
Abstract 13345: Efficacy and Safety of an Anticoagulation Clinic in Low-income Brazilian Patients With Heart Disease: a Randomized Clinical Trial
Authors: Maria A Martins, João A Oliveira, Daniel D Ribeiro, Cibele C César, Vandack A Nobre, Daniel M Palhares, Manoel O Rocha, Antonio L Ribeiro
Journal: Circulation (2014)

Introduction: Anticoagulation clinics (AC) have better impact on anticoagulation control than usual medical care (UMC). However, there is no randomized trial testing the results of AC in low-income realities. We sought to examine the performance of an AC in a group of patients treated at a Brazilian public hospital. Hypothesis: The assistance provided by AC presents difference in TTR when compared to the UMC. Methods: This was a randomized clinical trial to test the efficacy and safety of a recently-implemented AC over UMC in a group of outpatients with heart disease. The primary and secondary endpoints were time in the therapeutic range (TTR) and warfarin-associated complications, respectively. Overall, 280 patients were enrolled and randomly assigned to one of the two arms: group A: one year at AC (A1: first semester; A2: second semester); and group B: one semester receiving UMC (B1) and other at AC (B2). Results: The mean age was 56.8±13.1 years and patients were mostly female (54.6%). The median monthly income was 464 US dollars. Low literacy was predominant in this group of studied patients (&gt;68%). A1 showed higher TTR (62.4±20.8%) than B1 (55.1±28.5%) (p=0.014). An improvement of TTR was observed within group B, rising from 55.1±28.5% (B1) to 62.2±23.1% (B2) (p=0.008). A1 showed lower incidence rate (IR) per patients-year (p-y) of total bleedings than B1 (incidence rate ratio (IRR): 0.78; p=0.041) and a decline in the IR p-y was found for intra-group comparisons, both presenting IRR 0.58; p&lt;0.001. A1 showed lower IR p-y for thromboembolism than B1 (IRR=0.12; p=0.047). (Clinical trial registration: www.clinicaltrials.gov/. Identifier: NCT01006486) Conclusions: AC helped increase TTR and reduce warfarin-complications, even in low-income settings. Extending this assistance to similar populations in other Latin American countries could reduce hospitalizations and deaths related to warfarin use.
CO transfer factor on exercise: age and sex differences
Authors: A H Kendrick, G Laszlo
Journal: European Respiratory Journal (1990)

The effects of age and sex on the single-breath transfer factor (TLCO) estimated during exercise have been investigated in 80 normal subjects (40 men) divided equally into four groups: 1) 20-29 yrs; 2) 30-39 yrs; 3) 40-49 yrs and 4) 50-59 yrs. Oxygen consumption (VO2), cardiac frequency (fc), TLCO and transfer coefficient (KCO) were estimated at rest and at 25 W increments up to 100 W in women and 150 W in men. Quadratic regression equations were obtained for the relationships of TLCO and KCO to VO2, fc and workload (WL). TLCO and KCO at any WL, VO2 or fc were greatest in group 1 and least in group 4. The rate of decline of TLCO and KCO in men and women at l.min-1 VO2 was 0.063 and 0.031 mmol.min-1.kPa-1.yr-1 and 0.006 and 0.007 mmol.min-1.kPa-1.l-1.yr-1, respectively. Within each sex the curvilinearity of the relationships was similar regardless of age. At any WL, TLCO was greater in men than in women, whilst KCO was greater in women than in men. Sex differences were not abolished by correcting TLCO and KCO for anthropometric indices. We conclude that age and sex have significant effects on TLCO and KCO on exercise.
MECHANISMS INVOLVED IN THE DEPOSITION OF IMMUNE COMPLEXES IN TISSUES
Authors: Charles G. Cochrane
Journal: The Journal of Experimental Medicine (1971)

The mechanisms reponsible for the deposition of circulating immune complexes have been analyzed. An active process appears to be responsible in both a laboratory model in guinea pigs and in acute immune complex disease (serum sickness) in rabbits. In rabbits, after the injection of antigen to induce serum sickness, immune complexes appear in the circulation. In addition, homocytotropic (IgE) antibody is formed which binds to the surface of basophils. Leukocyte suspensions containing these basophils, when combined with specific antigen, release a soluble factor that causes clumping of platelets and release of their vasoactive amines. An excellent correlation was found between the presence of this mechanism of release of vasoactive amine and the deposition of immune complexes in serum sickness of rabbits. Antagonists of vasoactive amines or depletion of platelets, the major circulating reservoir of these amines, suppressed the deposition of circulating immune complexes and inhibited glomerulitis and arteritis. Upon entering the walls of vessels, the complexes became lodged immune complexes, greater than 19S in size, were deposited along the membranes. The data suggest that at a time when immune complexes appear in the circulation of an immunized rabbit, vasoactive amines are released from platelets in areas where turbulence of blood occurs. Sensitized basophils participate in the release of vasoactive amines from the platelets. The amines induced increased vascular permeability which leads to deposition of large complexes from the circulation in vessel walls by a process of filtration. The deposited complexes then induce inflammatory injury.
Physical activity and fatigue in subjects with COPD – A population based study
Authors: Mikael Andersson, Caroline Stridsman, Eva Rönmark, Anne Lindberg, Margareta Emtner
Journal: European Respiratory Journal (2014)

Introduction   Dyspnea and fatigue are cardinal symptoms of COPD, and reduced exercise capacity is frequently described. We aimed to assess physical activity levels in a population based sample of subjects with and without COPD, and to evaluate factors associated with low physical activity in these groups.   Methods   Data was collected in 2007-2008 from 470 subjects with COPD (FEV 1 /(F)VC)   Results   Low physical activity was significantly more prevalent in GOLD grade II and higher than Non-COPD (22.4 vs. 14.6 %, p=0.016). A history of heart disease, OR (CI 95%) 2.11 (1.10 - 4.08) and clinically significant fatigue, OR 2.33 (1.31 - 4.13) were the strongest factors associated with low physical activity in COPD, whereas obesity was the only significant factor in Non-COPD, OR 2.26 (1.17 – 4.35).   Conclusion   Physical activity levels are reduced in COPD grade II and higher. The factors associated with not reaching health enhancing levels of physical activity are different in COPD compared to Non-COPD. We propose that measurements of fatigue and a history of heart disease would be useful tools to include in the screening of subjects for pulmonary rehabilitation.
Allogeneic bone marrow transplantation for children with acute myeloblastic leukemia in first complete remission: impact of conditioning regimen without total-body irradiation--a report from the Société Française de Greffe de Moelle.
Authors: G Michel, E Gluckman, H Esperou-Bourdeau, J Reiffers, J L Pico, P Bordigoni, I Thuret, D Blaise, F Bernaudin, J P Jouet
Journal: Journal of Clinical Oncology (1994)

PURPOSE To analyze the French experience of chemotherapeutic preparation before human leukocyte antigen (HLA)-identical bone marrow transplantation (BMT) in children with acute myeloblastic leukemia (AML) in first complete remission (CR). PATIENTS AND METHODS The data base used for this study was a French BMT registry for childhood AML. Twenty-three children were conditioned with busulfan and 120 mg/kg cyclophosphamide (Bu-Cy 120 group). Nineteen received busulfan and 200 mg/kg cyclophosphamide (Bu-Cy200 group). During the same time period, 32 patients were prepared with total-body irradiation (TBI group) most often in combination with 120 mg/kg of cyclophosphamide. RESULTS The probability of relapse was 54%, 13%, and 10% for the Bu-Cy120, Bu-Cy200, and TBI groups, respectively (P &lt; .05 in the univariate analysis, log-rank test, 2 df). In the multivariate analysis, a conditioning regimen with Bu-Cy120 was significantly associated with a higher risk of relapse (P = .02; relative risk, 3.62). The probability of transplant-related mortality (TRM) was 0% for Bu-Cy120, 5% for Bu-Cy200, and 10% for TBI. Kaplan-Meier estimations of event-free survival (EFS) were 46% +/- 24%, 82% +/- 18%, and 80% +/- 14%, respectively, for the three groups, with median follow-up durations of 28 months (range, 3 to 78), 31 months (4 to 68), and 48 months (2 to 73). In the multivariate analysis, two factors adversely affected EFS: a conditioning regimen with Bu-Cy120 (P = .07) and a long interval from diagnosis to BMT (&gt; or = 120 days, P = .08). CONCLUSION Bu-Cy120 is a well-tolerated preparation, but results in a high risk of relapse for children with AML in first CR. This high risk of relapse is not observed when the dose of cyclophosphamide is increased to 200 mg/kg.
Hypoalbuminemia, cardiac morbidity, and mortality in end-stage renal disease.
Authors: R N Foley, P S Parfrey, J D Harnett, G M Kent, D C Murray, P E Barre
Journal: Journal of the American Society of Nephrology (1996)

A cohort of 432 ESRD (261 hemodialysis and 171 peritoneal dialysis) patients was followed up prospectively for an average of 41 months. Baseline and annual demographic, clinical, and echocardiographic assessments were performed, as well as serial clinical and laboratory tests measured monthly while patients were on dialysis therapy. Among hemodialysis patients, after adjustment was made for age, diabetes, and ischemic heart disease, as well as hemoglobin and blood pressure levels measured serially, a 10-g/L fall in mean serum albumin level was independently associated with the the development of de novo (relative risk [RR], 2.22; P = 0.001) and recurrent cardiac failure (RR, 3.84; P = 0.003), de novo (RR, 5.29; P = 0.001) and recurrent ischemic heart disease (RR, 4.24; P = 0.005), cardiac mortality (RR, 5.60; P = 0.001), and overall mortality (RR, 4.33; P < 0.001). Among peritoneal dialysis patients, a 10-g/L fall in mean serum albumin level was independently associated with the progression of left ventricular dilation as seen on follow-up echocardiography (beta, 13.4 mL/m2; P = 0.014), the development of de novo cardiac failure (RR, 4.16; P = 0.003), and overall mortality (RR, 2.06; P < 0.001). Hypoalbuminemia, a major adverse prognostic factor in dialysis patients, is strongly associated with cardiac disease.
Health Economic Analysis of the Randomized Multicenter Phase Ii Trial Sakk 77/08: Sorafenib with or Without Everolimus in Patients with Unresectable Hepatocellular Carcinoma (Hcc)
Authors: K. Matter-Walstra, M. Schwenkglenks, Q. Li, I. Cvijetic, B. Tschanz, P. Samaras, P. Saletti, A.D. Roth, D. Horber, D. Koeberle
Journal: Annals of Oncology (2014)
Inhibition of the Differentiation of Dendritic Cells From CD34+ Progenitors by Tumor Cells: Role of Interleukin-6 and Macrophage Colony-Stimulating Factor
Authors: C. Menetrier-Caux, G. Montmain, M.C. Dieu, C. Bain, M.C. Favrot, C. Caux, J.Y. Blay
Journal: Blood (1998)
Using NCCN Clinical Practice Guidelines in Oncology to Measure the Quality of Colorectal Cancer Care in the Veterans Health Administration
Authors: George L. Jackson, Leah L. Zullig, S. Yousuf Zafar, Adam A. Powell, Diana L. Ordin, Ziad F. Gellad, David Abbott, James M. Schlosser, Janis Hersh, Dawn Provenzale
Journal: Journal of the National Comprehensive Cancer Network (2013)

Clinical practice guidelines can be used to help develop measures of quality of cancer care. This article describes the use of a Cancer Care Quality Measurement System (CCQMS) to monitor these measures for colorectal cancer in the Veterans Health Administration (VHA). The CCQMS assessed practice guideline concordance primarily based on colon (14 indicators) and rectal (11 indicators) cancer care guidelines of the NCCN. Indicators were developed with input from VHA stakeholders with the goal of examining the continuum of diagnosis, neoadjuvant therapy, surgery, adjuvant therapy, and survivorship surveillance and/or end-of-life care. In addition, 9 measures of timeliness of cancer care were developed. The measures/indicators formed the basis of a computerized data abstraction tool that produced reports on quality of care in real-time as data were entered. The tool was developed for a 28-facility learning collaborative, the Colorectal Cancer Care Collaborative (C4), aimed at improving colorectal cancer (CRC) care quality. Data on 1373 incident stage I–IV CRC cases were entered over approximately 18 months and were used to target and monitor quality improvement activities. The primary opportunity for improvement involved surveillance colonoscopy and services in patients after curative-intent treatment. NCCN Clinical Practice Guidelines in Oncology were successfully used to develop a measurement system for a VHA research–operations quality improvement partnership.
Cardiorespiratory response to incremental exercise in asthma
Authors: Alice Gicquello, Stéphanie Fry, Rémi Neuvière, Benoit Wallaert
Journal: European Respiratory Journal (2014)

Background:  Asthma is a chronic inflammatory disease with varying severity, ranging from intermittent asthma to severe persistent asthma, and level of disease control. Some patients still report persistent dyspnea despite treatment of asthma. The aim of the study was to assess whether airways obstruction is the only factor explaining dyspnea in asthmatic patients.    Methods:   114 asthmatic patients (51.5 years ± 14) were included and divided into two groups: mild tomoderate persistent asthma (group 1, n=79) and severe persistent asthma (group 2, n=35). Spirometry and cardiopulmonary exercise testing were performed (prospective observational study CEPRO 2013-007).    Results:    Despite lower FEV1 in group 2, no difference was observed in aerobic capacity (VO 2 ) between both groups. Respiratory response was different during exercise. In group 2, patients developed a relative hypoventilation and exhausted their ventilatory reserve. In group 1, tachypnea was more pronounced.    Conclusion:   Exercise breathlessness among asthmatic patients is not related only to bronchial obstruction. In most severe cases, patients developed a respiratory response allowing them to adapt to their disability.