tbuckley/cabot-search huggingface dataset:
Development of a human COPD model-on-a-chip to mimic disease exacerbation (a small airway-on-a-chip model)
Authors: Kambez Hajipouran Benam, Remi Villenave, Carolina Lucchesi, Marc Mazur, Geraldine Hamilton, Donald Ingber
Journal: European Respiratory Journal (2014)

Acute exacerbations of COPD account for the high morbidity and mortality associated with the disease. Development of pharmacotherapies for COPD has been hindered partly by the lack of appropriate in vitro disease models.  Here, for the first time, we describe a biomimetic microfluidic microdevice that reconstructs the 3D mucosal lining of human small airways. Primary human airway epithelial cells from healthy normal and COPD donors were differentiated into ciliated pseudostratified epithelium in these small airway mimics. Validating the model, in line with earlier reports [Wang, R. et al. 2012; MacRedmond, R.E. et al. 2007] gene expression analysis revealed lower Toll-like Receptor (TLR)-4 transcripts in COPD compared with healthy normal. Of interest, when stimulating with TLR ligands to induce exacerbation-like phenotype, despite lower TLR levels, COPD chips mounted a more exaggerated inflammatory response.  A novel aspect of the chip technology is microfluidic 9vascular9 channel that allows simulation of endothelial cell-coated post-capillary venules to interrogate recruitment and attachment of circulating leukocytes. We re-created the complex organ-level response during exacerbation and compared efficacy of candidate therapeutics in modulating neutrophil adhesion to inflamed endothelium. The results demonstrated superiority of two anti-inflammatory drugs over a commonly prescribed corticosteroid in lowering neutrophilic inflammation. This new and unique technology provides the first 3D microfluidic system for modeling a human airway disease, may open path for personalized medicine, and can provide relevant feedback on efficacy and toxicity of drugs at preclinical stage.
The value of hepatic ultrasound and biochemical liver tests in screening for liver metastases.
Authors: M A Tempero, C A Williams, J C Anderson
Journal: Journal of Clinical Oncology (1986)

The records of 92 patients with a known diagnosis of extrahepatic cancer who had undergone hepatic ultrasound, biochemical liver tests (alkaline phosphatase, SGOT, lactic dehydrogenase, and bilirubin levels), and subsequent liver biopsy or autopsy within a 6-week period were reviewed. The sensitivity, specificity, and accuracy of the ultrasound and biochemical tests in the detection of metastatic liver disease were calculated. Although there was no significant difference in the sensitivity of either examination, the ultrasound demonstrated higher specificity and accuracy than the biochemical liver tests. The high sensitivity of hepatic ultrasound prevailed even in patients with normal biochemical liver tests. The sensitivity of hepatic ultrasound was significantly lower in patients with lymphoma compared with patients with colorectal cancer (50% v 100%, P less than .05). Notable incidental extrahepatic findings were reported in 25% of the ultrasound examinations. In institutions skilled in sonography, hepatic ultrasound may be a superior tool in the detection of liver metastases in most solid tumors, excluding lymphoma, and offers the additional advantage of simultaneous biliary tract and perihepatic visualization.
Preventing Low Back Pain in Industry
Authors: J. F. Kraus
Journal: JAMA (1998)

To the Editor.-Toaddress the racial disparity in cardiovascular disease (CVD), Dr Winkleby and colleagues 1 recommend the need for targeted intervention programs, changes in health policy reforms, and changes in the health care industry.These are indeed important remedies to reduce the growing health status gaps among women and men of color.It is equally important to better understand the role of different life experience as a potential pathway contributing to CVD risk factors among racial and ethnic populations.Winkleby et al report that a higher proportion of African American and Mexican American women lived below the poverty line compared with white women.They also report that African American women (with similar years of age as white women) were more likely to be unmarried and that Mexican American and African American women were also more likely to live in urban areas.Indeed, a higher proportion of Hispanic and African American women do in fact reside in crowded, urbanized settings; a higher proportion of single mothers are also African American. 2Economic, time, and residential constraints may therefore partially explain the higher constellation of interrelated primary risk factors observed among women of color in the study by Winkleby et al.Research shows higher socioeconomic status (SES) provides economic protection and reduces risk factor prevalence. 3 However, Winkleby et al show that African American and Mexican American women with the highest measure of SES (Ͼ12 years of education) had greater levels of risk factors compared with white women who have similar years of education.The rate of African American and Mexican American women with more than 12 years of education who were living in poverty was also double the rate among white women (18.9% and 18.6% vs 7.1%).Such information suggests that higher socioeconomic position may not provide equal protection among persons of color.Emerging evidence is beginning to establish a link between overt and subtle exposures to racial discrimination and higher levels of blood pressure among African Americans. 4 Racial discrimination as well as constraints on other aspects of the life experience may compete with positive lifestyle modification associated with the sequelae of less leisure-time exercise, overweight, hypertension, and diabetes among African American and Mexican American women.The president recently announced the Racial and Ethnic Health Disparities Initiative with the policy objective of eliminating health status disparities among racial and ethnic minorities by the year 2010. 5 The seminal work by Winkleby and colleagues highlights the need for investigators to design studies that not only assess genetic and behavioral determinants but also assess a priori hypotheses that quantify the relative role different life contraints contribute as a pathway to CVD risk factors among men and women of color.The subsequent challenge is for policymakers to develop tools and instruments that will effectively intervene at both individual and societal levels.
Prostaglandin E Production by Lewis Lung Carcinoma: Mechanism for Tumor Establishment In Vivo&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M R Young, S Knies
Journal: JNCI Journal of the National Cancer Institute (1984)

Prostaglandin E (PGE) concentrations in supernatants of in vitro cultured Lewis lung carcinoma (LLC) cells were measured by radioimmunoassay. Growth of cells correlated with an increase in PGE concentrations in the media. This elevation of PGE in the LLC supernatant could be prevented by the culturing of the cells with indomethacin, a prostaglandin synthesis inhibitor. Serum PGE levels of LLC-implanted mice were also measured. As the tumors developed in vivo, the systemic levels of PGE increased. For examination of the in vivo effect of PGE2 on tumor growth, LLC-implanted C57BL/6 mice were treated with exogenous PGE2, which resulted in an increase in the frequency of tumor establishment. In contrast, oral administration of indomethacin to LLC-implanted mice resulted in a reduced rate of tumor establishment, growth, and metastasis. A relationship between PGE2 production by tumor cells and their survival in a host was indicated.
Cyclic 3′,5′-adenosine monophosphate in human blood platelets
Authors: Edwin W. Salzman, Linda Levine
Journal: Journal of Clinical Investigation (1971)

The relation of cyclic 3′,5′-adenosine monophosphate to platelet function has been studied by investigating the influence of this compound and of its N6-2′-0-dibutyryl derivative on platelet aggregation and other aspects of platelet behavior after demonstration of adenyl cyclase activity in disrupted platelets.
Administration of Growth Hormone to Underweight Patients with Chronic Obstructive Pulmonary Disease
Authors: LUC BURDET, BENOÎT de MURALT, YVES SCHUTZ, CLAUDE PICHARD, JEAN-WILLIAM FITTING
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Patients with chronic obstructive pulmonary disease (COPD) often develop weight loss, which is associated with increased mortality. Recombinant human growth hormone (rhGH) treatment has been proposed to improve nitrogen balance and to increase muscle strength in these patients. The aim of this study was to assess the effects of rhGH administration on the nutritional status, resting metabolism, muscle strength, exercise tolerance, dyspnea, and subjective well-being of underweight patients with stable COPD. Sixteen patients attending a pulmonary rehabilitation program (age: 66 ± 9 yr; weight: 77 ± 7% of ideal body weight; FEV1: 39 ± 13% of predicted) were randomly treated daily with either 0.15 IU/kg rhGH or placebo during 3 wk in a double-blind fashion. Measurements were made at the beginning (D0) and at the end (D21) of treatment and 2 mo later (D81). Body weight was similar in the two groups during the study, but lean body mass was significantly higher in the rhGH group at D21 (p < 0.01) and D81 (p < 0.05). The increase in lean body mass was 2.3 ± 1.6 kg in the rhGH group and 1.1 ± 0.9 kg in the control group at D21 and 1.9 ± 1.6 kg in the rhGH group and 0.7 ± 2.1 kg in the control group at D81. At D21, the resting energy expenditure was increased in the rhGH group (107.8% of D0, p < 0.001 compared with the control group). At D21 and D81, the changes in maximal respiratory pressures, handgrip strength, maximal exercise capacity, and subjective well-being were similar in the two groups. At D21, the 6-min walking distance decreased in the rhGH group ( − 13 ± 31%) and increased in the control group ( + 10 ± 14%; p < 0.01). We conclude that the daily administration of 0.15 IU/kg rhGH during 3 wk increases lean body mass but does not improve muscle strength or exercise tolerance in underweight patients with COPD.
Gender-related association between respiratory stability and Cheyne-Stokes respiration in chronic heart failure - A matched control study
Authors: Thomas Bitter, Solvey Roman-Garcia, Zisis Dimitriadis, Britta Körber, Christian Prinz, Dieter Horstkotte, Jost Niedermeyer, Olaf Oldenburg
Journal: European Respiratory Journal (2012)

Introduction: Hypersensitive ventilatory feedback loop has major impact on the manifestation of Cheyne-Stokes respiration (CSA) in chronic heart failure (CHF). As CSA mainly affects male CHF patients (pts), this study aims to clarify the role of respiratory stability in the evolution of CSA in men and women.  Methods: We investigated 563 pts with CHF (91 female, LVEF ≤45%, NYHA-class ≥2) using echocardiography, cardiopulmonary exercise testing (CPX), cardiorespiratory polygraphy, measurement of hyperoxic, hypercapnic ventilatory response (HCVR), and standard laboratory. Adjusted for age (±2 years), body mass index (BMI; ± 2), and LVEF (± 3%) 79 matched pairs (male/female) were eligible for analysis.  Results: Obstructive sleep apnoea (AHI ≥5/h) was present in 12 female (15.2%) and 13 male (16.4%) pts (p=n.s.), CSA (AHI ≥5/h) in 30 (37.9%) female and 54 (68.4%) male pts (p 2  36.7 (interquartile range (IQR) 34.4-39.4) vs. 36.7 (IQR 34.8-38.7), VE/VCO 2  slope during CPX 34 (IQR 30-40) vs. 35 (IQR 31-40), HCVR 2.32 (IQR 1.71-3.49) vs. 2.69 (IQR 2.01-4.45) did not show a significant difference. Adjusted for age, NYHA-class, BMI, heart rate, LVEF, CRP, creatinine, NT-proBNP stepwise regression analysis revealed HCVR (p=0.03) an independent predictor for CSA in male pts while NYHA-class (p=0.04) was the only independent predictor for CSA in female pts.  Conclusion: These data suggest gender-related differences in the evolution of CSA. Additional studies are warranted to figure out a more sophisticated pathophysiological concept that may elucidate these findings.
How to Choose Frontline Therapy for Chronic Myelogenous Leukemia: So Many Drugs, Not So Many Patients
Authors: Paul J. Shami
Journal: Journal of the National Comprehensive Cancer Network (2012)

With the development of tyrosine kinase inhibitors (TKIs), the management and outlook for patients with chronic myelogenous leukemia (CML) have completely changed over the past 10 years. Imatinib was the first TKI approved to treat CML in the chronic phase. After their initial approval as second-line agents, dasatinib and nilotinib were compared with imatinib in the first-line setting in 2 randomized trials. Both trials showed that therapeutic milestones (complete cytogenetic remission and major molecular remission) occurred earlier with these newer agents, leading to their approval for the treatment of newly diagnosed CML. Therefore, 3 different TKIs are now available for treating CML. Long-term follow-up of patients treated with imatinib shows that the attainment of therapeutic milestones by 12 months of therapy leads to better long-term outcomes. Most patients who experience disease progression on imatinib do so within the first 3 years of therapy. Therefore, one can argue that dasatinib or nilotinib should be chosen to treat patients with newly diagnosed CML. However, these agents do not have the long-term track record of imatinib. This article summarizes the published data and reviews the rationale in choosing the appropriate TKI for first-line treatment of CML in the chronic phase.
A new plan for the future of the hospital system
Authors: Doug Payne
Journal: BMJ (2000)

After a two year consultative process, the Republic of Ireland's “medical manpower” forum has come up with a new plan for the future of the country's hospital system. A significant increase in the number of consultants over the next five years is planned, as well as a reduction in the number of junior doctors.

The 50 page report—from a panel of representatives from the main medical organisations, health board officials, and hospital managers—says that the current balance between …
Does alpha1-antitrypsin augmentation therapy slow the annual decline in FEV1 in patients with severe hereditary alpha1-antitrypsin deficiency? Wissenschaftliche Arbeitsgemeinschaft zur Therapie von Lungenerkrankungen (WATL) alpha1-AT study group
Authors: N Seersholm, M Wencker, N Banik, K Viskum, A Dirksen, A Kok-Jensen, N Konietzko
Journal: European Respiratory Journal (1997)

Patients with severe hereditary alpha1-antitrypsin deficiency (alpha1-ATD) face a high risk of developing emphysema at a young age. Intravenous augmentation therapy with purified human alpha1-antitrypsin (alpha1-AT) is now available. However, a controlled trial to show its efficacy has never been carried out. The aim of this study was to compare the decline in forced expiratory volume in one second (deltaFEV1) between Danish patients who had never received augmentation therapy and German patients treated with weekly infusion of alpha1-AT. From the files of the Danish alpha1-ATD register, 97 exsmokers, with a PiZ phenotype and for whom results of at least two lung function measurements with an interval of at least 1 yr were available, were identified. From a German group of patients treated with weekly infusions of alpha1-AT, 60 mg x kg(-1) body weight, 198 exsmokers, with biannual lung function measurements were identified. The deltaFEV1 was compared between the two treatment groups by random effects modelling. The deltaFEV1 in the treated group was significantly lower than in the untreated group, with annual declines of 53 mL x yr(-1) (95% confidence interval (95% CI) 48-58 mL x yr(-1)) and 75 mL x yr(-1) (95% CI 63-87 mL x yr(-1)), respectively (p=0.02). The two groups differed with respect to gender and initial FEV1% predicted. Gender did not have any influence on the deltaFEV1. Stratification by initial FEV1% pred showed a significant effect of the treatment only in the group of patients with an initial FEV1% pred of 31-65%, and deltaFEV1 was reduced by 21 mL x yr(-1). This nonrandomized study suggests that weekly infusion of human alpha1-antitrypsin in patients with moderately reduced lung function may slow the annual decline in forced expiratory volume in one second.
Correlation of Mycobacterium tuberculosis ¬-specific and non-specific quantitative T cell IFN-γ responses with mycobacillary load in a HIV-prevalent high burden setting
Authors: Grant Theron, Jonny Peter, Laura Lenders, Richard van-Zyl Smit, Richard Meldua, Ureshnie Govender, Keertan Dheda
Journal: European Respiratory Journal (2012)

Background: Measures of bacillary load in patients with tuberculosis (TB) may be useful for predicting and monitoring response to treatment. The relationship between quantitative T-cell responses and mycobacterial load is poorly studied. We hypothesised that, in a high burden setting, the magnitude of mycobacterial antigen-specific and non-specific T-cell IFN-γ responses would correlate with (a) bacterial load and (b) culture conversion in patients undergoing treatment.  Methods: We compared the magnitude of purified-protein-derivative (PPD) and RD1-specific (TSPOT.TB and QFT-GIT) peripheral blood IFN-γ T-cell responses with associates of sputum bacillary load [liquid culture time-to-positivity, smear-microscopy grade, Xpert-MTB/RIF Ct values, and the presence of cavities on a chest radiograph] in 513 individuals with suspected TB in Cape Town, South Africa. Serial IGRA responses were evaluated at 2 (n=35) and 6 months (n=13) post-treatment initiation.  Results: PPD and RD1-specific IFN-γ responses were not associated with culture TTP (p-values for TSPOT.TB, QFT-GIT and PPD of 0.11, 0.07 and 0.09), smear-grade (0.42, 0.09, and 0.85), Ct values (0.70, 0.91, and 0.49) or the presence of cavities on the chest radiograph (0.12, >0.05, and 0.08). 2-month IGRA conversion rates (positive to negative) were negligible [  Conclusions: In a high-burden setting M.tuberculosis-specific and non-specific antigen-driven IFN-γ responses do not correlate with bacillary load and are not useful for prognostication or treatment monitoring.
Effect of a non‐sedative antihistaminic (loratadine) in moderate asthma
Authors: A. DIRKSEN, T. ENGEL, L. FRØLUND, J. H. HEINIG, U. G. SVENDSEN, B. WEEKE
Journal: Allergy (1989)

Seventeen patients with perennial asthma, stable on a moderate dose of inhaled steroid, participated in a crossover study comparing the clinical effect of a non‐sedative, potent and highly selective H 1 antagonist (loratadine 10 mg) with placebo. Each treatment period began with 2 weeks run‐in followed by 8 weeks on either antihistamine or placebo. During the 8‐week periods inhaled steroid was gradually tapered according to a fixed scheme. One patient was withdrawn from active treatment and three from placebo periods because of decreasing lung function ( P &gt; 0.1). Among the remaining 13 patients there was a threefold (1.8–4.8) decrease in the bronchial sensitivity to histamine during treatment with antihistamine compared to placebo ( P &lt; 0.01). There was a trend in favour of active treatment with regard to changes in all symptom scores, lung function and use of escape medication, but these differences were not statistically significant. The increase in FEV, was &lt; 5% of predicted normal ( P &lt; 0.05). We concluded that the bronchial response to histamine can be attenuated by loratadine, an oral H 1 receptor antagonist, but further studies are necessary to assess the clinical usefulness and place of loratadine in the therapy of asthma.
Ossification in Abdominal Scars<sup>1</sup>
Authors: Ndu Eke, Alexander J Warrington
Journal: Journal of the Royal Society of Medicine (1981)

Three cases of heterotopic ossification in abdominal scars are presented. The aetiology and pathogenesis of this condition are discussed with reference to the literature. Awareness of its occurrence will prevent anxiety and unnecessary investigations. When symptomatic, the treatment is local excision with or without local irradiation.
Idiopathic pleuritis: Truth or myth?
Authors: Georgia Hardavella, Dimitrios Zachilas, Georgia Doga, Nikolaos Anastasiou
Journal: European Respiratory Journal (2013)

Objective: To determine the presence or not of idiopathic pleuritis in patients that underwent medical thoracoscopy(MT)   Materials and methods: Retrospective study of 750 patients (1998-2011) that underwent MT under conscious and local sedation. Assessment of clinicopathological status/results and clinical follow up in the thoracic outpatients clinic.   Results:  Thirty two patients were excluded from the group of patients with undiagnosed pleural effusion (histology report:systemic disease or parapneumonic effusion).152/770 patients(20.2%)were classified as idiopathic pleuritis (sinister and any other underlying pathology was excluded) and underwent long term surveillance. Mean surveillance was 4.1 years(2months–9years). During that time 2/152 was diagnosed with lung cancer. 3/152 presented pleural effusion recurrence without any signs of malignancy/systemic disease and underwent talc pleurodesis.   Conclusions:  Undiagnosed pleural effusions constitute a large group among the pleural effusion patients. This group is associated with favourable patient outcome and encouraging prognosis especially when the diagnosis is set by MT under conscious sedation.
Efficacy and safety of antiretrovirals in HIV-infected patients with cancer
Authors: H.A. Torres, V. Rallapalli, A. Saxena, B.P. Granwehr, G.M. Viola, E. Ariza-Heredia, J.A. Adachi, R.F. Chemaly, R. Marfatia, Y. Jiang, P. Mahale, A. Kyvernitakis, M.A. Fanale, V. Mulanovich
Journal: Clinical Microbiology and Infection (2014)
Preoperative chemoradiation followed by transhiatal esophagectomy for carcinoma of the esophagus: final report.
Authors: A A Forastiere, M B Orringer, C Perez-Tamayo, S G Urba, M Zahurak
Journal: Journal of Clinical Oncology (1993)

PURPOSE In 1990 we published the results of an intensive 3-week preoperative chemoradiation regimen for locoregional esophageal cancer that suggested improved survival compared with historical controls. We now report the long-term results at a median follow-up of 78.7 months. PATIENTS AND METHODS Forty-three patients with locoregional squamous cell carcinoma or adenocarcinoma of the esophagus or cardia were treated with fluorouracil (5-FU), cisplatin, and bolus vinblastine concurrent with radiation administered over 21 days. Transhiatal esophagectomy was performed on day 42. RESULTS Forty-one patients (95%) completed the preoperative treatment, and 36 (84%) had a potentially curative resection. Ten of 41 (24%) had no tumor in the resected esophagus and nodal tissues (path-negative group). The median survival duration of all 43 patients registered on study was 29 months; 34% were alive at 5 years. By histology, median survival durations were 32 months for 21 adenocarcinoma patients and 23 months for 22 squamous cell patients, with corresponding 5-year survival rates of 34% and 31%, respectively. Analysis of the 36 patients who underwent a potentially curative resection demonstrated median survival durations of 32 and 44 months and 5-year survival rates of 36% and 43%, respectively, for adenocarcinoma and squamous cell histologies. Path-negative (complete response [CR]) patients had a median survival duration of 70 months and 60% were alive at 5 years, while those patients with residual tumor in the resected esophagus had a median survival duration of 26 months and 32% were alive at 5 years (P = .114 by the log-rank test and P = .04 by the Wilcoxon test). CONCLUSION The results of this regimen appear improved over those reported with surgery alone, with an approximate doubling of the 5-year survival rate. Thirty-two percent of patients with residual tumor in the esophageal specimen are long-term survivors, which suggests a benefit from esophagectomy. A randomized trial is in progress to compare this preoperative regimen with immediate surgery.