tbuckley/cabot-search huggingface dataset:
Sealed-lips instruction for pressurised metered dose inhalers (pMDIs) – A critical step?
Authors: Mark Sanders, Ronald Bruin, Cuong Tran
Journal: European Respiratory Journal (2014)

Background : pMDI inserts include the mouthpiece instruction: close around/hold firmly between the lips. The perfect seal for laboratory testing may not, however, be representative of patient use.   Aim : To determine gap-effects on salbutamol delivery from low (LR) and high resistance (HR), and breath-actuated (BA)/training pMDIs.   Methods : Sealed and 0.18cm 2 gap adapters, and modified actuators to mimic low and high pMDI resistances were made. The four combinations were tested with Ventolin® Evohaler® (+standard actuator=Control), using a Next Generation Impactor™ operated to pharmacopoeial standard. The effect of sealed, small and large gaps (0.18 and 0.45 cm 2 ) on the activation flow rate of salbutamol Autohaler®, Easi-Breathe® and the pMDI trainer Trainhaler®+Flo-Tone® were tested using a 1L/min/step waveform generator (MH Custom Design & Mfg LC, USA).   Results : Pairwise comparisons of calculated lung dose % (stages 3-5, Table 1) indicated that resistance and gap significantly influenced lung dose; resistance more so. Activation flow rates were significantly larger (P   Conclusion : The sealed-lips instruction particularly affected non-BA pMDI lung dose from low resistance devices, but is unlikely to be detectable clinically. The instruction is critical for BA devices, and may impact clinically where patients use both types of device. Sealed lips should remain the default instruction.
Association of gastro-esophageal reflux disease symptoms with COPD severity and acute exacerbations of COPD
Authors: Konstantinos Bartziokas, Andriana Papaioannou, Stamatoula Tsikrika, Foteini Karakontaki, Zoi Nouvaki, Alexis Papadopoulos, Emmanouil Kastanakis, Napoleon Karagiannidis, Stelios Loukides, Spyros Papiris, Aikaterini Haniotou, Konstantinos Kostikas
Journal: European Respiratory Journal (2012)

Background: Gastroesophageal reflux disease (GERD) is common in COPD patients but there is little prospective data on the impact of GERD on COPD exacerbations.  Objectives: To evaluate the association of GERD and GERD-related therapy with disease severity and exacerbation frequency in COPD patients.  Methods: 1087 COPD patients and 392 controls were included. GERD symptoms were evaluated with GERD-Q questionnaire and treatment with proton pump inhibitors (PPIs) was recorded. All patients were contacted monthly and acute exacerbations of COPD (AECOPD) and hospitalizations for COPD exacerbations were recorded.  Results: The presence of significant GERD symptoms was more common in COPD patients compared to controls (25.4 vs. 9.0%, p  Conclusions: GERD symptoms are significantly associated with COPD exacerbations and hospitalizations and treatment with PPIs is related to less exacerbations and hospitalizations.
Appropriate Evaluation and Treatment of Heart Failure Patients After Implantable Cardioverter-Defibrillator Discharge
Authors: Joseph D. Mishkin, Sherry J. Saxonhouse, Gregory W. Woo, Thomas A. Burkart, William M. Miles, Jamie B. Conti, Richard S. Schofield, Samuel F. Sears, Juan M. Aranda
Journal: Journal of the American College of Cardiology (2009)
Challenges in the Management of Older Patients With Colon Cancer
Authors: Efrat Dotan, Ilene Browner, Arti Hurria, Crystal Denlinger
Journal: Journal of the National Comprehensive Cancer Network (2012)

Most patients with colon cancer are older than 65 years. Their treatment poses multiple challenges, because they may have age-related comorbidities, polypharmacy, and physical or physiologic changes associated with older age. These challenges include limited data on the ability to predict tolerance to anticancer therapy and the appropriate use of treatment modalities in the setting of comorbidity and concurrent frailty. The low number of older patients enrolled in large clinical trials results in a paucity of evidence to guide oncologists in the appropriate management of this population. In early-stage disease, clinical dilemmas arise regarding the ability of older patients to undergo successful curative surgical procedures and the risk/benefit ratio of adjuvant chemotherapy. The management of metastatic disease raises questions regarding the clinical benefit of various anticancer therapies and the role of combination therapy with possible increased toxicity in the noncurative setting. Overall, the available evidence shows that fit older patients are able to tolerate treatment and derive similar clinical benefits to younger patients. Limited data are available to guide treatment for less-fit, more-vulnerable older patients. This lack of data leads to variations in treatment patterns in older adults, making them less likely to receive standard therapies. This review provides an overview of the available data regarding the management of older adults with colon cancer in the adjuvant and metastatic settings.
Analysis of the lethal outcomes in patients with severe pneumonia
Authors: Rustem Khamitov
Journal: European Respiratory Journal (2014)

Some factors besides treatment can significantly influence on the fatal outcomes of pneumonia. Objective. Identification of non-medication risk factors of death based on study of the inpatients clinical signs of pneumonia. Methods. Retrospective analyze of 62 case histories of patients died from pneumonia in hospitals: 12 women and 50 men of 30 to 88 years. Results. 24% of patients had constant job, 76% were not working. 21% of patients had a disability for chronic diseases. The beginning of disease averaged 5,4 days before hospitalization. The recourse was on average 1 day before hospitalization. The most frequent complaints were cough (10% with hemoptysis), weakness and dyspnea. 45% of patients smoked. 50% abused alcohol. Dipsomania preceded hospitalization in 40% of cases. 10% had a drug addiction, 5% were HIV-positive, 13% had chronic viral hepatitis B and C. Leading role of cardiovascular (66%) and gastrointestinal (65%) pathology have been revealed. Based on dates of autopsies, attention should be paid to alcoholic genesis of these diseases. Coronary heart disease and hypertension took place much rarer. In 40% we observed various stages of consciousness disturbance from mild lethargy to coma. In 69% we saw skin and mucosa cyanosis, in 63% - tachypnea, 55% - hypotension. 57% had body mass deviations. In 63% we observed bilateral pneumonia, in 33% - pleural effusion. Conclusions. Social status, late hospitalization, smoking, alcoholism, alcoholic genesis of comorbidity, deviation of the mental, nutritive status, bilateral pneumonia, pleural effusion, hemodynamic disorders should be recognized as non-medication predictors of fatal outcome, requiring early attention and subsequent correction of treatment.
Anti-inflammatory therapy for sarcoidosis patients
Authors: Vladimir Romanov, Svetlana Shelukhina, Eugene Shmelev
Journal: European Respiratory Journal (2013)

Aim: To evaluate effectiveness of fenspiride in treatment for sarcoidosis.  Materials and methods: We studied 42 sarcoidosis patients, which received fenspiride. They received fenspiride 240 mg/day (one tablet 3 times a day) for 4 months. The study included: clinical examination (anamnesis, physical examination), laboratory tests (blood assay, inflammatory proteins), chest X-ray and CT, evaluation of immunology status and external respiration function, bronchoscopy with BAL study and transbronchial lung biopsy.  Spontaneous regression of the process was excluded by the dynamic observation without treatment during 6 months.  The diagnosis was verified morphologically and the active phase of the process was established in all the cases.  The discussed treatment resulted in positive clinical and X-ray dynamics in 64% cases, and the disease progressing was observed only in 12% cases on treatment. Fenspiride was withdrawn in the latter group and treatment with systemic corticosteroids was administered. 6 patients (14%) developed adverse gastrointestinal reactions, which were easily controlled by symptomatic treatment.  Conclusions:  1. Fenspiride has demonstrated high effectiveness (61%) in treatment for sarcoidosis with a low proportion of adverse reactions (14%).  2. Administration of fenspiride 240 mg/day for 4 months is indicated to patients with different forms of active sarcoidosis.
Commentary 1 on “Effects of acute prednisolone administration on exercise endurance and metabolismEffects of acute prednisolone administration on exercise endurance and metabolism”
Authors: Michel Audran
Journal: British Journal of Sports Medicine (2008)

Synthetic glucocorticoids are frequently used in sports because of their potent anti-inflammatory and analgesic effects. These drugs have many side effects, particularly glucocorticoid-induced adrenal insufficiency. This pharmacological class …
Simultaneous Immunohistochemical Detection of Tumor Cells in Lymph Nodes and Bone Marrow Aspirates in Breast Cancer and Its Correlation With Other Prognostic Factors
Authors: Bernd Gerber, Annette Krause, Heiner Müller, Dagmar Richter, Toralf Reimer, Josef Makovitzky, Christina Herrnring, Udo Jeschke, Günther Kundt, Klaus Friese
Journal: Journal of Clinical Oncology (2001)

PURPOSE: We studied the prognostic and predictive value of immunohistochemically detected occult tumor cells (OTCs) in lymph nodes and bone marrow aspirates obtained from node-negative breast cancer patients. All were classified as distant metastases-free using conventional staging methods. PATIENTS AND METHODS: A total of 484 patients with pT1-2N0M0 breast cancer and 70 with pT1-2N1M0 breast cancer and a single affected lymph node participated in our trial. Ipsilateral axillary lymph nodes and intraoperatively aspirated bone marrow were examined. All samples were examined for OTCs using monoclonal antibodies to cytokeratins 8, 18, 19. Immunohistological findings were correlated with other prognostic factors. The mean follow-up was 54 ± 24 months. RESULTS: OTCs were detected in 180 (37.2%) of 484 pT1-2N0M0 patients: in the bone marrow of 126 patients (26.0%), in the lymph nodes of 31 patients (6.4%), and in bone marrow and lymph nodes of 23 (4.8%) patients. Of the 70 patients with pT1-2N1MO breast cancer and a single involved lymph node, OTCs were identified in the bone marrow of 26 (37.1%). The ability to detect tumor cells increased with the following tumor features: larger size, poor differentiation, and higher proliferation. Tumors of patients with OTCs more frequently demonstrated lymph node invasion, blood vessel invasion, higher urokinase-type plasminogen activator levels, and increased PAI-1 concentrations. Patients with detected OTCs showed reduced disease-free survival (DFS) and overall survival (OAS) rates that were comparable to those observed in patients who had one positive lymph node. Multivariate analysis of prognostic factors revealed that OTCs, histological grading, and tumor size are significant predictors of DFS; OTCs and grading of OAS. CONCLUSION: OTCs detected by simultaneous immunohistochemical analysis of axillary lymph nodes and bone marrow demonstrate independent metastatic pathways. Although OTCs were significantly more frequent in patients with other unfavorable prognostic factors, they were confirmed as an independent prognostic factor for pT1-2N0M0, R0 breast cancer patients.
Sustained efficacy from 3 to 6 months following bronchoscopic thermal vapor ablation (BTVA) in the treatment of heterogeneous emphysema
Authors: Felix Herth, Gregory Snell, Peter Hopkins, Kim Baker, Christian Witt, Mark H. Gotfried, Arshang Valipour, Manfred Wagner, Franz Stanzel, Jim Egan, Steven Kesten, Armin Ernst
Journal: European Respiratory Journal (2011)

Background:  A recent approach to bronchoscopic lung volume reduction (LVR), BTVA, involves the localized application of thermal energy through heated water vapor to targeted areas of emphysematous lung in order to induce LVR.   Objectives:  Evaluate efficacy and safety of BTVA in the treatment of heterogeneous emphysema during a clinical trial.   Methods:  Open-label, single-arm trial of BTVA in patients with upper lobe predominant emphysema (n=44). Entry criteria: FEV 1  15% - 45% predicted, RV>150%, TLC>100%, 6MWD>140 m, DLCO>20%, previous pulmonary rehabilitation. Primary efficacy endpoint: FEV 1  and SGRQ at 6 months. Other endpoints included FVC, RV, FRC, TLC, mMRC dyspnea, 6MWD.   Results:  No procedural complications (mean procedure time=30 min). Lung function changes from baseline (mean (SE)) are summarized in the following table:  At 6 months, FEV 1  improvement was ≥12% in 55%. SGRQ improved by 14 (2) units with 73% of patients improving ≥4units, 6MWD increased 47 (11), mMRC improved 0.9 (0.2) units, BODE score improved 1.4 (0.3) units (all p   Conclusion:  Unilateral lobar BTVA treatment of heterogeneous emphysema results in clinically significant improvements in multiple efficacy endpoints that are sustained from 3 to 6 months.
A multicentre, randomised, double blind, placebo controlled phase II study of subcutaneous interferon beta-1a in the treatment of patients with active rheumatoid arthritis
Authors: J van Holten
Journal: Annals of the Rheumatic Diseases (2004)

To assess the efficacy of interferon beta (IFN beta) in combination with methotrexate in treatment of patients with rheumatoid arthritis.209 patients with active rheumatoid arthritis, who had been on methotrexate for at least six months and at a stable dose for four weeks before study entry, were randomised in double blind fashion to receive placebo (0.05 ml or 0.5 ml), IFN beta 2.2 microg (0.05 ml), or IFN beta 44 microg (0.5 ml), given subcutaneously three times weekly for 24 weeks. The primary efficacy measure was a change in radiological scores at week 24. The secondary endpoint was the proportion of patients who met the ACR 20% improvement criteria at the end of the study. Synovial biopsy specimens were obtained before and after treatment from a subset of patients. Immunohistochemistry was used to detect the presence of inflammatory cells and the results were measured by digital image analysis. Collagen crosslinks were measured in urine at different times throughout the study.Analysis of radiological scores and clinical variable showed no changes in any of the groups, and there were no differences between the groups. On microscopic analysis of synovial tissue there was no significant change in the scores for infiltration by inflammatory cells after IFN beta treatment. Urinary levels of collagen crosslinks were unchanged between the treatment groups.At the doses tested, treatment with IFN beta three times weekly in combination with methotrexate did not have a clinical or radiological effect in patients with rheumatoid arthritis.
Retinoic Acid Stimulation of the Induction of Mouse Killer T-Cells in Allogeneic and Syngeneic Systems&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: G Dennert, C Crowley, J Kouba, R Lotan
Journal: JNCI Journal of the National Cancer Institute (1979)

The ability of retinoic acid (RA), a potent antitumor agent, to stimulate cell-mediated cytotoxicity (CMC) in mice was investigated. Low doses of RA (5-300 micrograms/mouse/day) administered ip into C57BL/6 mice for 5 days daily or for 1--3 months three times a week before immunization in vivo or in vitro with allogeneic BALB/c S194 myeloma cells led to an enhanced cytotoxic activity of their spleen effector cells. Similarly, in a syngeneic situation injection of RA into C57BL/6 or BALB/c mice before in vitro challenge with EL 4 (C57BL/6) or S194 (BALB/c) tumor cells strongly stimulated CMC. The enhanced cytotoxic activity was effected by thymus-derived lymphocytes (T-cells) and specific for the H-2 histocompatibility antigens in the case of the allogeneic sensitization or specific for tumor antigens in the case of the syngeneic sensitization. Because RA had no effect on the effector step of CMC, RA likely enhanced the induction step of T-CMC. The action of RA was antigen-dependent, and it is therefore a true adjuvant rather than a nonspecific stimulator or polyclonal activator of cytotoxic T-cells.
Prospective molecular monitoring of minimal residual disease after non-myeloablative allografting in newly diagnosed multiple myeloma
Authors: M Ladetto, S Ferrero, D Drandi, M Festuccia, F Patriarca, N Mordini, S Cena, R Benedetto, G Guarona, F Ferrando, L Brunello, P Ghione, V Boccasavia, R Fanin, P Omedè, L Giaccone, A Palumbo, R Passera, M Boccadoro, B Bruno
Journal: Leukemia (2015)
Lymphoid Neoplasms in Rats After Inoculation With Cell-Free Extracts of Leukemic AKR Mice&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: W. H. Kirsten, C. E. Platz, J. S. Flocks
Journal: JNCI Journal of the National Cancer Institute (1962)

Cell-free filtrates from AKR mice with spontaneous lymphoid leukemia were injected intravenously, in doses of 0.05 ml per animal, into 90 noninbred newborn Wistar rats. Thirty-four of 79 weaned rats (43%) developed leukemia between 14 and 49 weeks of age. Female recipients of leukemic cell-free filtrates became leukemic at a significantly higher rate than males. Littermate controls received heat-inactivated (60° to 65° C for 30 min) cell-free filtrates from identical AKR donors. None of the 49 control rats died of leukemia after the age of 18 to 28 months. Serial cell-free transmission of leukemia through 3 generations of newborn rats increased the percentage of rats with leukemia from 43 to 92 percent and reduced the mean survival time between inoculation and leukemia death from 22 to 10 weeks. Leukemias arising in rats after cell-free filtrate injection were transplantable by the intraperitoneal route into 47 of 47 newborn rats and into 7 of 90 young adult rats, particularly when large doses of leukemic cells were injected. Similar leukemic-cell grafts failed to grow in young adult AKR mice. Three probably related forms of lymphoid neoplasms were observed: lymphoid leukemias, thymic lymphosarcomas with metastases but without leukemic blood involvement, and abdominal lymphosarcoma. Lymphoid leukemias (81 %) accounted for the majority of lymphoid neoplasms in rats. No tumors attributable to the polyoma virus were found in rats given injections of cell-free filtrates, but polyoma-virus infection was found in 4 littermates of 123 rats tested for HI antibodies.
Multifunctional roles of gelsolin in health and diseases
Authors: Guo Hua Li, Pamela D. Arora, Yu Chen, Christopher A. McCulloch, Peter Liu
Journal: Medicinal Research Reviews (2010)

Abstract Gelsolin, a Ca 2+ ‐regulated actin filament severing, capping, and nucleating protein, is an ubiquitous, multifunctional regulator of cell structure and metabolism. More recent data show that gelsolin can act as a transcriptional cofactor in signal transduction and its own expression and function can be influenced by epigenetic changes. Here, we review the functions of the plasma and cytoplasmic forms of gelsolin, and their manifold impacts on cancer, apoptosis, infection and inflammation, cardiac injury, pulmonary diseases, and aging. An improved understanding of the functions and regulatory mechanisms of gelsolin may lead to new considerations of this protein as a potential biomarker and/or therapeutic target.
Occupational health screening of salon workers in Kandy,Sri Lanka
Authors: Dushantha Madegedara, Kavinda Amerasinghe, Tharanga Wijethilake, Damith Nandadeva, Sumedha Samankantha
Journal: European Respiratory Journal (2014)

Our objective was to screen the respiratory and general health of a group of salon workers who are at risk due to exposure to cosmetics containing a variety of chemicals.  A descriptive cross sectional study was done among a randomly selected sample of salon workers in the Kandy city.  Demographic data, duration of exposure, use of protective gear, present and past illnesses, allergies and smoking habits and ventilation were documented with an interviewer administered questionnaire. Examination, Spirometry using Spirolab 3, and CXR were performed in all. 78 salon workers(53females) with mean age 32.6(range 19-63) were studied. Respiratory symptoms were present in 36(46%) of the subjects; shortness of breath 27(34.6%), cough 19(24.30%),wheezing 07(8.9%),rhinitis09(11.5%).All but onehad developed symptoms after employment. 17(21.7%)had skin allergies, of which 7(8.9%) were allergic specifically to the chemical used at work.Spirometrywas normal in 60(76.9%) and restrictive in 18(23%). CXR was abnormal in 32(41%) with nodular opacities9, prominent pulmonary arteries 3,air trapping 3, bronchiectasis 2, fibrosis 2and pleural thickening 1.Otherco-morbidity were Musculo-skeletal 5, Hypertension 10, Dermatological1,Subfertility 3andNon specific headache 9.12(58%) were active smokers (mean pack years 2.65) and 58.3% of them had respiratory symptoms.Protective gear was used irregularly by 57(73%) of the workers including mask50(64%),apron 46(58.9%)and gloves 22(28%).Ventilation was inadequate in 72%.  The majority of subjects had developed respiratory symptoms after employment and further study is needed to find the association. Education and regulation regarding chemical use and protective measures is advocated.
-2 Agonists in sport: are the anti-doping rules meeting the needs of asthmatic athletes?
Authors: J Naranjo Orellana, M D Carranza Márquez
Journal: British Journal of Sports Medicine (2009)

Objectives (a) To review the methacholine tests performed in our laboratory up until 2008; (b) to compare them with previously reported data in 2006 and (c) to examine if the anti-doping rules are meeting the needs of asthmatic athletes who really need bronchodilator treatment. Methods Between April 2004 and September 2008, 89 high-level athletes were examined in our laboratory in order to obtain an abbreviated therapeutic use exemption for β-2 agonists. Of these, 50 men (23.31 (7.05) years) and 23 women (20.68 (5.94) years) performed a methacholine inhalation test with increasing concentrations of methacholine (0.025, 0.25, 2.5, 5, 10 and 25 mg/ml) until a fall of 20% in forced expiratory volume in 1 s (FEV 1 ) was achieved. Results 31 candidates (42.5%) had a provocative concentration causing a 20% fall in FEV 1 (PC 20 ) &lt;2 mg/ml; 12 (16.4%) were between 2 and 4 mg/ml; 8 (11%) between 4.1 and 8 mg/ml and 22 candidates (30.1%) had a PC 20 &gt;8 mg/ml. Seven of the 73 candidates had an obstructive pattern in the spirometry at rest, demonstrated by a FEV 1 % &lt;70% but with a FEV 1 &gt;70% of the reference value. Conclusions The anti-doping regulations with respect to β-2 agonists need to be reviewed, and measures should be adopted to include a fall of 70% in FEV 1 % as an obstruction criterion to indicate a bronchodilation test and to extend the criterion for a positive methacholine test to a PC 20 of 8 mg/ml.
Donald Walker Barritt
Authors: G. K. S. Jordan
Journal: BMJ (2015)

Donald Walker (“Bill”) Barritt’s first child was born in 1946 with complex congenital heart disease, and this undoubtedly strengthened his interest in cardiology. After national service he undertook a research lectureship in Bristol, studying the effects of familial hypercholesterolaemia in the genesis of coronary artery disease. He was appointed as consultant physician and cardiologist …