tbuckley/cabot-search huggingface dataset:
The Cost Effectiveness of Early Treatment with Fluticasone Propionate 250 μ g Twice a Day in Subjects with Obstructive Airway Disease
Authors: GUIDO VAN DEN BOOM, MAUREEN P. M. H. RUTTEN-VAN MÖLKEN, JOHAN MOLEMA, PRASANNA R. S. TIRIMANNA, CHRIS VAN WEEL, CONSTANT P. VAN SCHAYCK
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

In a two-stage detection program, subjects with signs of obstructive airway disease were selected from a random sample of the general population. Subjects (n = 82) were randomly assigned to either fluticasone propionate 250 μ g twice a day or placebo twice a day via pMDI in a 1-yr, double-blind trial if they met criteria for persistent airway obstruction, increased bronchial hyperresponsiveness, or a rapid decline in FEV1. Main outcome measures were postbronchodilator FEV1, quality-adjusted life years (QALYs), and direct medical cost. Secondary measures were prebronchodilator FEV1, PC20, health-related quality of life (CRQ), symptom-free weeks, episode-free weeks, exacerbations, and indirect cost. Subgroup analysis was based on reversibility of obstruction. Analysis revealed a significant gain in postbronchodilator FEV1 (98 ml/yr; p = 0.01) in favor of fluticasone. Only subjects with reversible obstruction showed an improvement in PC20 (1.4 doubling dose; p = 0.03). Early treatment resulted in 2.7 QALYs gained per 100 treated subjects (p = 0.17) and in a clinically relevant improvement in dyspnea (CRQ; p < 0.03). The incremental cost effectiveness ratios were US$13,016/QALY for early treatment and US$33,921/QALY for the combination of detection and treatment. The incremental cost for one additional subject with a clinically relevant difference in dyspnea was US$1,674. In conclusion, early intervention with fluticasone resulted in significant health gains at relatively low financial cost.
Effects of Lymphoma on the Peripheral Nervous System
Authors: R A C Hughes, T Britton, M Richards
Journal: Journal of the Royal Society of Medicine (1994)

Peripheral nervous system abnormalities occur in 5% of patients with lymphoma and have a wide differential diagnosis. Herpes zoster is the commonest cause. Vinca alkaloids are the only drugs used in lymphoma which commonly cause neuropathy. Compression or infiltration of nerve roots by lymphoma is a rare presenting feature but becomes more common with advanced disease. Radiation plexopathy does not usually develop until at least 6 months after irradiation and can be difficult to distinguish from neoplastic infiltration. Either multifocal infiltration of nerves or lymphoma-associated vasculitis may present as a peripheral neuropathy. The incidence of Guillain-Barré (GBS) syndrome, and possibly chronic idiopathic demyelinating polyradiculoneuropathy, appears to be increased in association with lymphoma, especially Hodgkin's disease. Subacute sensory neuronopathy and subacute lower motor neuronopathy have both been reported as paraneoplastic syndromes associated with Hodgkin's disease. Treatment of the underlying lymphoma is only rarely followed by recovery of the associated neuropathy.
Noninvasive positive pressure ventilation in elderly patients with acute respiratory failure due to severe pneumonia
Authors: Yutaka Yokoyama, Hiroyuki Taniguchi, Yasuhiro Kondoh, Tomoki Kimura, Kensuke Kataoka, Ryuichi Hasegawa
Journal: European Respiratory Journal (2011)

This study was retrospective observational study of Noninvasive positive pressure ventilation (NPPV) in elderly (≥ 65 yrs) patients with acute respiratory failure (ARF) due to severe pneumonia. The aim of this study was to evaluate the clinical characteristics, prognosis, predictors of failure of NPPV in elderly patients with ARF due to severe pneumonia including do-not-intubate (DNI) status. Elderly patients with ARF due to pneumonia who receive NPPV as a first line intervention (n=46) were enrolled retrospectively during 2002-2009.  The mean (± SD) APACHE II and age were 22±6 and 80±7 yrs, and the NPPV success rate and 90-day mortality rate were 48% and 52%, respectively. The DNI patients were 21 cases, 46% of the whole, and NPPV success rate and 90-day mortality rate was 51% and 71%, respectively. In multivariate analysis, pH >7.44 at basal (OR7.41, 95%CI 1.14-48.11) and PaO2/FIO2 ≤ 135 after 24 hours (OR16.83, 95%CI 2.23-124.89) were independently associated with failure of NPPV. Failure of NPPV (OR25.3, 95%CI 2.70-236.79) and DNI status (OR13.2, 95%CI 1.32-131.81) were independently associated with the risk factors for 90-day death.  It was acceptable to perform NPPV as a first line therapy for elderly ARF patients severe pneumonia, including DNI status.
The effects of obstructive sleep apnea on cardiovascular functioning in children with obesity
Authors: Anna Rita Mazzotta, Giuliano Tocci, Silvia Miano, Simona Bianchi, Alessandra Tabarrini, Martina Forlani, Maria Pia Villa
Journal: European Respiratory Journal (2013)

Background : Paediatric obesity and obstructive sleep apnea (OSA) may be associated with cardiovascular consequences and they may show the same common inflammatory and metabolic pathogenesis.   Aim : to evaluate and to assess cardiovascular activity in children with obesity associated with OSA.   Methods : Obese children (body mass index - BMI - percentile >95°) underwent to standard polysomnography in a standard laboratory setting, a blood sample for lipid profile and a 24-hour ambulatory blood pressure monitoring. It was calculated the Smoothness Index (SI) which is a parameter to evaluate the blood pressure variability.   Results : We studied 38 children (mean age 10.04±3.2 years, 28 males), with a mean BMI of 27.57±4.02, a mean BMI percentile of 117.81±21.52. They had an apnea-hypopnea index of 11.98±20.49n/h, an overnight oxygen saturation of 96.74±2.47 %. They did not show the physiologic systolic nocturnal deep of blood pressure. SI was higher in children with apnea-hypopnea index (AHI) > 5 n/h. BMI percentile correlates positively with systolic blood pressure, diurnal and nocturnal, while HDL (high-density lipoprotein) plasma levels correlate inversely.   Conclusions : preliminary data showed that obese children with OSA had a peculiar blood pressure profile since they did not show the physiologic nocturnal deep. Obese children with AHI > 5 n/h were exposed to a future major risk of cardiovascular consequences.
The PESI, the simplified PESI and the shock index for identification of high-risk and low-risk patients with acute pulmonary embolism
Authors: Burcu Koyden, Fusun Alatas, Selma Metintas
Journal: European Respiratory Journal (2012)

We compared the test characteristics of the pulmonary embolism severity index (PESI), the simplified pulmonary embolism severity index (sPESI) and shock index (SI) for predicting 30-day outcomes in a prospective study of 132 patients with objectiveliy confirmed pulmonary embolism (PE). The primary outcome of the study was 30-day mortality.  Overall, 13 (9,8%) out of 132 patients died during the first month. The SI classified fewer patients as high-risk (41 (31,1%) out of 132 patients, compared to sPESI (45 (34,1%) and compared to PESI (57 (43,2%). High-risk patients based on the SI had a higher mortality than those based on the sPESI and PESI (31,7% versus 22,2% and17,5%). Low-risk patients based on the SI had a lower mortality than those based on sPESI and PESI (0% versus 3,4% and 4%).  The SI quantified the prognosis of patients with PE beter than sPESI and PESI.
Construction and validation of a practical prognostic index for patients with metastatic breast cancer.
Authors: N Yamamoto, T Watanabe, N Katsumata, Y Omuro, M Ando, H Fukuda, Y Takue, M Narabayashi, I Adachi, S Takashima
Journal: Journal of Clinical Oncology (1998)

PURPOSE To identify the readily available prognostic factors most helpful in predicting survival and to construct and validate a prognostic index for metastatic breast cancer (MBC) patients. PATIENTS AND METHODS Data from 233 MBC patients, accrued on a multiinstitutional randomized phase III trial (Japan Clinical Oncology Group [JCOG] study 8808), were analyzed to identify significant prognostic factors and a prognostic index was constructed by incorporating these prognostic factors. For validation of the prognostic index, another data set from 315 consecutive MBC patients, who had been treated with standard anthracycline-containing regimens, was analyzed. RESULTS In multivariate regression analyses, history of adjuvant chemotherapy (ADJCT) (P = .0005), presence of distant lymph nodes (DLNs) (P = .0117) and liver (HEP) (P = .0099) metastases, elevation of serum lactate dehydrogenase (LDH) (P &lt; .0001), and shorter disease-free interval (DFI) (P &lt; .0001) significantly contributed to poorer survival. The prognostic index was constructed as follows: Prognostic Index = ADJCT (not received = 0, received = 1) + DLNs (absent = 0, present = 1) + HEP (absent = 0, present = 1) + LDH (&lt; or = one times normal = 0, &gt; one times normal = 1) + DFI (&gt; or = 24 months = 0, &lt; 24 months = 2). With this prognostic index, patients could be stratified into three risk groups. The median survival times (MSTs) of low-, intermediate- and high-risk groups were 45.5, 24.6, and 10.6 months, respectively (P &lt; .0001). This prognostic index was applied to the validation patients. The respective MSTs for each risk group were 49.6,22.8, and 10.0 months (P &lt; .0001). CONCLUSION ADJCT, DLNs, HEP, LDH, and DFI were important prognostic factors for MBC patients. The prognostic index readily enables MBC patients to be stratified into three risk groups and is worth considering for future clinical trials.
The association between asthma, atopic diseases and metabolic factors in a young population of southern Taiwan
Authors: Tsu-Yu Yuan, Li-Yu Wang, Teng-Hui Huang, Ru-Ling Hsiao, Tsu-Nai Wang
Journal: European Respiratory Journal (2011)

Background:  Previous studies have suggested that obesity and cholesterol may play a role in the susceptibility for asthma. The relationship between cholesterol concentrations, asthma and atopic diseases is still controversial.   Objective:  The aim of this study was to investigate whether metabolic factors are associated with asthma and atopic diseases.   Methods:  The cross-sectional study sampled randomly 6838 subjects ≤ 18 years old from elementary, junior and senior high schools in southern Taiwan. All subjects completed questionnaire interview, weight and height data measurements and blood sample collection. Allergic disorders were determined by the subjects ever been diagnosed by a doctor. Body mass index (BMI), blood pressures, the levels of triglyceride and total cholesterol were measured.   Results:  We found a significant association between high concentrations of cholesterol and dermatitis in girls (aOR = 1.56, p = 0.002) and rhinitis in boys (aOR = 1.31, p = 0.038) after adjusting for potential confounding factors. Obesity was statistical significant associated with dermatitis (p = 0.008) and rhinitis (p = 0.038). The interaction effect of cholesterol and obesity on dermatitis was significant (p = 0.032). We did not find that cholesterol and triglyceride concentrations were associated with asthma.   Conclusion:  We found that high concentrations of cholesterol were associated with dermatitis in girls and rhinitis in boys. Obesity and high concentrations of cholesterol may increase the risk of dermatitis.
Hypoxia-Induced WSB1 Promotes the Metastatic Potential of Osteosarcoma Cells
Authors: Ji Cao, Yijie Wang, Rong Dong, Guanyu Lin, Ning Zhang, Jing Wang, Nengming Lin, Yongchuan Gu, Ling Ding, Meidan Ying, Qiaojun He, Bo Yang
Journal: Cancer Research (2015)

Abstract Intratumoral hypoxia occurs in many solid tumors, where it is associated with the development of metastatic character. However, the connections between these phenomena are not fully understood. In this study, we define an integrative role for the E3 ubiquitin ligase subunit WSB1. In primary osteosarcomas, increased levels of WSB1 correlated with pulmonary metastatic potential. RNAi-mediated attenuation of WSB1 or disruption of its E3 ligase activity potently suppressed tumor metastasis. Quantitative proteomic and functional analyses revealed that WSB1 ubiquitylates the Rho-binding protein RhoGDI2 and promotes its proteasomal degradation, thereby activating Rac1 to stimulate tumor cell motility and invasion. Our findings show how WSB1 regulates key steps of the metastatic cascade in hypoxia-driven osteosarcoma, and they highlight a candidate therapeutic target to potentially improve the survival of patients with metastatic disease. Cancer Res; 75(22); 4839–51. ©2015 AACR.
Audit of the impact of increased nurse education in diagnosis and management of patients with airflow obstruction in the community
Authors: Roger Wolstenholme, Marie Barrowclough, Patricia Darley, Gillian Prescott
Journal: European Respiratory Journal (2012)

AIMS. Primary. To improve skills of primary care clinicians in diagnosis and management of patients with airflow obstruction and to provide more effective and consistent care. Secondary. To reduce self reported COPD and asthma exacerbations over a 12 month period, improve patient outcomes including MRC scores, patient satisfaction surveys and increased use of self management plans. To increase a multidisciplinary approach in the management of COPD and increase self reported competency of primary care nurses. METHODS. 10 community practices applied and were accepted for clinical mentorship. Following an Education Needs Analysis a practice nurse education programme was developed and provided by specialist nurses and community respiratory physician. In the 10 practices 259 patients were identified as having poorly controlled asthma or COPD. 213 attended for review, 63 with an initial diagnosis of asthma and 150 COPD. RESULTS. 12 of 63 (20%) patients with asthma showed no reversibility, 11 of 150 (6%) of COPD patients had normal spirometry. 90% of the asthmatics and 93% COPD pts were uncontrolled, 2 or more courses of steroids and antibiotics a year. After the programme this was reduced to 3% and 12% respectively. COPD MRC scores improved markedly, MRC 3 37% to 17%, MRC 4 30% to 13%. 50% of COPD patients were referred and accepted pulmonary rehabilitation. DISCUSSION. Increased education supported by continued mentorship improves clinical competencies and outcomes by better diagnosis, appropriate inhaled therapy and encouraging multidisciplinary working. Continued mentorship is vital to maintain standards and confidence in primary care.
Is primary ciliary dyskinesia a "biofilm" disease?
Authors: Woolf Walker, Claire Jackson, Peter Lackie, Rob Howlin, Allan Ray, Faust Saul, Jane Lucas, Luanne Hall-Stoodley
Journal: European Respiratory Journal (2012)

Introduction 

Bacterial biofilms are structured communities of adherent bacteria enveloped in self-produced matrix which are refractory to antibiotics and the host immune response. They play a key role in the chronicity of respiratory infection in cystic fibrosis. Haemophilus influenzae is the most common pathogen isolated in primary ciliary dyskinesia (PCD). We hypothesise that impaired mucociliary clearance in PCD will predispose these patients to biofilm infections.

Aims 

To investigate the biofilm-forming capacity of clinical H. influenzae isolates from PCD patients.

Methods 

The biofilm-forming ability of 4 H. influenzae clinical isolates from different PCD patients were compared using a crystal violet (CV) assay, colony forming unit counts (CFUs), fluorescence in situ hybridisation (FISH) and scanning electron microscopy (SEM).

Results 

CV staining demonstrated bacterial biomass adherent to plastic for all isolates (OD600 0.04 for isolate 1 to 0.12 for isolate 4, p<0.05). SEM permitted visualisation of a characteristic matrix surrounding the bacteria. Biofilm thickness varied for each isolate, qualified by FISH (13μm for isolate 1; 82μm for isolate 4). CFUs quantified the number of viable bacteria within each day 4 biofilm, ranging from 9x106 CFU/cm2 in isolate 1 to 2x108 CFU/cm2 in isolate 4.

Conclusion 

We have characterised biofilm-forming capacity in all 4 H. influenzae isolates from PCD patients. 2 isolates from chronically colonised patients (over 4 years) consistently formed thicker, cell dense and structurally more complex biofilms than the other, more recently isolated, strains. These data suggest that H. influenzae is capable of biofilm formation and that PCD patients, like cystic fibrosis, might harbour bacteria in biofilms.
Efficacy and safety of oxantel pamoate in school-aged children infected with Trichuris trichiura on Pemba Island, Tanzania: a parallel, randomised, controlled, dose-ranging study
Authors: Wendelin Moser, Said M Ali, Shaali M Ame, Benjamin Speich, Maxim Puchkov, Jörg Huwyler, Marco Albonico, Jan Hattendorf, Jennifer Keiser
Journal: The Lancet Infectious Diseases (2015)
Interstitial Lung Disease in Japanese Patients with Lung Cancer
Authors: Shoji Kudoh, Harubumi Kato, Yutaka Nishiwaki, Masahiro Fukuoka, Kouichiro Nakata, Yukito Ichinose, Masahiro Tsuboi, Soichiro Yokota, Kazuhiko Nakagawa, Moritaka Suga, Haiyi Jiang, Yohji Itoh, Alison Armour, Claire Watkins, Tim Higenbottam, Fredrik Nyberg
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: Interstitial lung disease (ILD) occurs in Japanese patients with non–small cell lung cancer (NSCLC) receiving gefitinib.Objectives: To elucidate risk factors for ILD in Japanese patients with NSCLC during treatment with gefitinib or chemotherapy.Methods: In a prospective epidemiologic cohort, 3,166 Japanese patients with advanced/recurrent NSCLC were followed for 12 weeks on 250 mg gefitinib (n = 1,872 treatment periods) or chemotherapy (n = 2,551). Patients who developed acute ILD (n = 122) and randomly selected control subjects (n = 574) entered a case-control study. Adjusted incidence rate ratios were estimated from case-control data by odds ratios (ORs) with 95% confidence intervals (CIs) using logistic regression. Crude (observed) incidence rates and risks were calculated from cohort data.Measurements and Main Results: The observed (unadjusted) incidence rate over 12 weeks was 2.8 (95% CI, 2.3–3.3) per 1,000 person-weeks, 4.5 (3.5–5.4) for gefitinib versus 1.7 (1.2–2.2) for chemotherapy; the corresponding observed naive cumulative incidence rates at the end of 12-week follow-up were 4.0% (3.0–5.1%) and 2.1% (1.5–2.9%), respectively. Adjusted for imbalances in risk factors between treatments, the overall OR for gefitinib versus chemotherapy was 3.2 (1.9–5.4), elevated chiefly during the first 4 weeks (3.8 [1.9–7.7]). Other ILD risk factors in both groups included the following: older age, poor World Health Organization performance status, smoking, recent NSCLC diagnosis, reduced normal lung on computed tomography scan, preexisting chronic ILD, concurrent cardiac disease. ILD-related deaths in patients with ILD were 31.6% (gefitinib) versus 27.9% (chemotherapy); adjusted OR, 1.05 (95% CI, 0.3–3.2).Conclusions: ILD was relatively common in these Japanese patients with NSCLC during therapy with gefitinib or chemotherapy, being higher in the older, smoking patient with preexisting ILD or poor performance status. The risk of developing ILD was higher with gefitinib than chemotherapy, mainly in the first 4 weeks.
Differential Effect of Number of Previous Episodes of Affective Disorder on Response to Lithium or Divalproex in Acute Mania
Authors: Alan C. Swann, Charles L. Bowden, Joseph R. Calabrese, Steven C. Dilsaver, David D. Morris
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: The authors investigated the relationship between number of lifetime episodes of affective disorder and the antimanic response to lithium, divalproex, or placebo. METHOD: The subjects were 154 of the 179 inpatients with acute mania who entered a 3-week parallel group, double-blind study. The primary efficacy measure was the manic syndrome score from the Schedule for Affective Disorders and Schizophrenia. The relationship between improvement and number of previous episodes was investigated by using nonlinear regression analysis. RESULTS: An apparent transition in the relationship between number of previous episodes and response to antimanic medication occurred at about 10 previous episodes. For patients who had experienced more episodes, response to lithium resembled the response to placebo but was worse than response to divalproex. For patients who had experienced fewer episodes, however, the responses to lithium and divalproex did not differ and were better than the response to placebo. This differential response pattern was not related to rapid cycling or mixed states. CONCLUSIONS: A history of many previous episodes was associated with poor response to lithium or placebo but not to divalproex.
GAS6 Inhibits Granulocyte Adhesion to Endothelial Cells
Authors: Gian Carlo Avanzi, Margherita Gallicchio, Flavia Bottarel, Loretta Gammaitoni, Giuliana Cavalloni, Donatella Buonfiglio, Manuela Bragardo, Giorgio Bellomo, Emanuele Albano, Roberto Fantozzi, Giovanni Garbarino, Brian Varnum, Massimo Aglietta, Giuseppe Saglio, Umberto Dianzani, Chiara Dianzani
Journal: Blood (1998)
Solubilized myocardial adenylate cyclase
Authors: Gerald S. Levey, Irwin Klein
Journal: Journal of Clinical Investigation (1972)

We have recently described the preparation of a solubilized cat myocardial adenylate cyclase which is unresponsive to histamine, norepinephrine, glucagon, and thyroxine, the hormones which activate the particulate enzyme. Since hormone receptors may consist of proteins and phospholipids, we determined the effect of several phospholipids on restoring the responsiveness of the solubilized adenylate cyclase to histamine. The addition of phosphatidylserine completely restored the histamine-mediated activation of the solubilized enzyme in contrast to phosphatidylethanolamine and phosphatidylinositol which were without effect. The concentration of histamine producing half-maximal activation of adenylate cyclase, 2 × 10-5 M, was virtually identical with that observed in the particulate preparation. The antihistamine, diphenhydramine, 8 × 10-5 M, abolished activation of adenylate cyclase by histamine in both the solubilized and particulate preparations. Phosphatidylserine also restored glucagon responsiveness, but did not restore norepinephrine responsiveness. It would appear that phosphatidylserine produced the necessary molecular configuration of the adenylate cyclase for histamine binding and activation of the enzyme.