tbuckley/cabot-search huggingface dataset:
Noninvasive Assessment of Airway Alterations in Smokers
Authors: Sylvia Verbanck, Daniël Schuermans, Marc Meysman, Manuel Paiva, Walter Vincken
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

It has been shown that structural changes in small airways of smokers with average smoking histories greater than 35 pack-years could be reflected in the single-breath washout test. The more sophisticated multiple breath washout test (MBW) has the potential to anatomically locate the affected small airways in acinar and conductive lung zones through increased phase III slope indices S(acin) and S(cond), respectively. Pulmonary function, S(acin), and S(cond) were obtained in 63 normal never-smokers and in 169 smokers classified according to smoking history (< 10 pack-years; 10-20 pack-years; 20-30 pack-years; > 30 pack-years). Compared with never-smokers, significant changes in S(acin) (p = 0.02), S(cond) (p < 0.001), and diffusing capacity (DL(CO); p < 0.001) were detected from greater than 10 pack-years onwards. Spirometric abnormality was significant only from greater than 20 pack-years onwards. In smokers with greater than 30 pack-years and DL(CO) less than 60% predicted, the presence of emphysema resulted in disproportionally larger S(acin) than S(cond) increases. We conclude that S(cond) and S(acin) can noninvasively detect airway changes from as early as 10 pack-years onwards, locating the earliest manifestations of smoking-induced small airways alterations around the acinar entrance. In these early stages, the associated DL(CO) decrease may be a reflection of ventilation heterogeneity rather than true parenchymal destruction. In more advanced stages of smoking-induced lung disease, differential patterns of S(acin) and S(cond) are characteristic of the presence of parenchymal destruction in addition to peripheral airways alterations.
Abstract P265: Plasma Phospholipid Trans Fatty Acids, Cardiovascular Diseases, and Total Mortality: The Cardiovascular Health Study
Authors: Qianyi Wang, Fumiaki Imamura, Rozenn N Lemaitre, Eric B Rimm, Frank M Sacks, Donna Spiegelman, Irena B King, Xiaoling Song, Hongyan Huang, David Siscovick, Dariush Mozaffarian
Journal: Circulation (2013)

Introduction: Whereas trans fatty acids (TFAs) have generally been evaluated as a group, emerging evidence suggests that trans18:2, but not trans18:1 or trans16:1, isomers are especially adverse for health. Few studies have investigated how biomarkers of different TFA isomers relate to CVD or total mortality. Objective: To examine prospective associations of circulating trans16:1n9 (16:1n9t), total trans18:1 (18:1t, the sum of 18:1n5-12), and n9cis/n6trans, n9trans/n6cis, and n9trans/n6trans 18:2 (18:2ct, 18:2tc, 18:2tt) with incident CVD events and total mortality. Methods: We prospectively evaluated 2,788 adults in the Cardiovascular Health Study, age 72±5y, free of prevalent CVD, and having plasma phospholipid TFA measures from blood stored in 1992. CVD events and mortality were centrally adjudicated through 2010, including total mortality, CVD death, CHD death, nonfatal MI (NFMI), and ischemic stroke. Risk associated with each TFA was assessed using Cox proportional hazards adjusting for sociodemographics, lifestyle, dietary habits, prevalent diseases, and the 5 TFA mutually. Results: During 31,863 person-years, 1,681 deaths occurred including 581 CVD and 373 CHD deaths; as well as 383 NFMI and 328 ischemic strokes. 18:2ct was associated with higher CVD mortality (quintile 5 vs. 1 HR 1.48, 95%CI 0.98-2.23, p trend 0.04), but not total mortality or nonfatal CVD events. 18:2tc was related to higher NFMI (HR 1.69, 95%CI 1.06-2.69, p trend&lt;0.01), while 18:2tt was not significantly associated with mortality or CVD endpoints. Similarly, 16:1n9t was positively associated with NFMI (HR 2.96, 95%CI 1.80-4.88, p trend&lt;0.01), and ischemic stroke (HR 2.00, 95%CI 1.19-3.36, p trend 0.02), but not mortality endpoints. 18:1t was associated with lower CVD (HR 0.52, 95%CI 0.34-0.79, p trend=0.01) and CHD (HR 0.49, 95%CI 0.29-0.84, p trend 0.02) mortality, but these findings for 18:1t were substantially (~50%+) weakened when analyses did not mutually adjust for all 5 TFA, which were intercorrelated (r -0.08 to 0.78). Conclusions: Specific 18:2 TFA isomers, 18:2ct and 18:2tc but not 18:2tt, as well as 16:1n9t are prospectively associated with higher incidence of CVD events. 18:1t is associated with lower CVD risk, perhaps owing at least partly to co-adjustment for multiple correlated TFAs. The general specificity of all findings for CVD events, rather than total mortality or non-CVD mortality, is consistent with adverse physiologic effects of TFA on CVD risk factors. These results highlight the need for further investigation of effects and determinants of specific TFA subclasses and isomers.
Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer.
Authors: A Webb, D Cunningham, J H Scarffe, P Harper, A Norman, J K Joffe, M Hughes, J Mansi, M Findlay, A Hill, J Oates, M Nicolson, T Hickish, M O'Brien, T Iveson, M Watson, C Underhill, A Wardley, M Meehan
Journal: Journal of Clinical Oncology (1997)

PURPOSE We report the results of a prospectively randomized study that compared the combination of epirubicin, cisplatin, and protracted venous infusion fluorouracil (5-FU) (ECF regimen) with the standard combination of 5-FU, doxorubicin, and methotrexate (FAMTX) in previously untreated patients with advanced esophagogastric cancer. PATIENTS AND METHODS Two hundred seventy-four patients with adenocarcinoma or undifferentiated carcinoma were randomized and analyzed for survival, tumor response, toxicity, and quality of life (QL). RESULTS The overall response rate was 45% (95% confidence interval [CI], 36% to 54%) with ECF and 21% (95% CI, 13% to 29%) with FAMTX (P = .0002). Toxicity was tolerable and there were only three toxic deaths. The FAMTX regimen caused more hematologic toxicity and serious infections, but ECF caused more emesis and alopecia. The median survival duration was 8.9 months with ECF and 5.7 months with FAMTX (P = .0009); at 1 year, 36% (95% CI, 27% to 45%) of ECF and 21% (95% CI, 14% to 29%) of FAMTX patients were alive. The median failure-free survival duration was 7.4 months with ECF and 3.4 months with FAMTX (P = .00006). The global QL scores were better for ECF at 24 weeks, but the remaining QL data showed no differences between either arm of the study. Hospital-based cost analysis on a subset of patients was similar for each arm and translated into an increment cost of $975 per life-year gained. CONCLUSION The ECF regimen results in a survival and response advantage, tolerable toxicity, better QL and cost-effectiveness compared with FAMTX chemotherapy. This regimen should now be considered the standard treatment for advanced esophagogastric cancer.
Cancer-associated hemolytic-uremic syndrome: analysis of 85 cases from a national registry.
Authors: J B Lesesne, N Rothschild, B Erickson, S Korec, R Sisk, J Keller, M Arbus, P V Woolley, L Chiazze, P S Schein
Journal: Journal of Clinical Oncology (1989)

A registry of suspected cases of cancer-associated hemolytic-uremic syndrome (C-HUS) was established in May 1984. Records of 85 patients from the registry, all with history of cancer, hematocrit less than or equal to 25%, platelet count less than 100,000, and serum creatinine greater than or equal to 1.6 mg/dL were subjected to in-depth analysis. Eighty-nine percent of patients had adenocarcinoma, including 26% with gastric cancer. Microangiopathic hemolysis was reported in 83 patients; coagulation studies were normal with rare exception. Bone marrow examination ruled out chemotherapy-induced myelosuppression in 68 of 85. Thirty-five percent of patients were without evident cancer at time of syndrome development. Mitomycin (MMC) was part of the treatment regimen in 84 patients; all but nine received a cumulative dose greater than 60 mg. Pulmonary edema, generally noncardiogenic, developed in 65% of patients, often after blood product transfusions. C-HUS has a high mortality: over 50% of patients died of or with syndrome, most within 8 weeks of syndrome development. Conventional treatment was ineffective, although ten of 21 treated with staphylococcal protein A (SPA) immunopheresis showed significant responses. Statistical analysis found only absence of obvious tumor and treatment with SPA to suggest favorable prognosis. C-HUS is distinguishable from related syndromes such as childhood HUS, thrombotic thrombocytopenic purpura (TTP), consumption coagulopathy, and microangiopathic hemolysis associated with advanced carcinoma. MMC is likely involved in the development of C-HUS; the risk of developing C-HUS after treatment with MMC is between 4% and 15%. However, possible bias in patients referred to the registry and reports of non-MMC C-HUS cases must be remembered. Recommendations include careful monitoring of renal and hematologic function in patients treated with MMC, aggressive nontransfusion in patients with suspected C-HUS, and consideration of treatment with SPA immunopheresis in patients with definite syndrome.
Characterization of lymphocyte subsets in the lungs of smokers and patients with COPD
Authors: Helena Forsslund, Mikael Mikko, Johan Grunewald, Åsa Wheelock, Jan Wahlström, Magnus Sköld
Journal: European Respiratory Journal (2011)

Background:  COPD is characterized by chronic inflammation in the lungs. CD8+ T cells but in more severe disease also CD4+ T cells, have been implicated in the pathogenesis. T cell maturation entails distinct stages which can be identified based on their expression of the surface markers CD45RA and CD27. By combining these markers it is possible to distinguish naive and memory/effector subpopulations. We investigated whether these T cell subpopulations in bronchoalveolar lavage (BAL) differ in COPD patients compared to smokers with normal lung function and never-smokers.   Methods:  Bronchoscopy and BAL was performed on 24 never-smokers, 20 smokers with normal lung function and 20 COPD patients (14 smokers and 6 ex-smokers). The frequencies of major lymphocyte subsets and the differentiation status of CD4+ and CD8+ T cells were analyzed by flow cytometry.   Results:  There were higher percentages of CD8+ T cells in smokers and CD56+ T cells in smokers and COPD patients compared to never-smokers (p   Conclusions:  The higher percentages of cytotoxic T cells in smokers and COPD patients may be related to smoking-induced tissue damage. The increased percentage of central memory cells in COPD smokers suggests an ongoing immune response. Smoking cessation resulted in a normalization of CD4+ central/effector memory cells in BAL, indicating a reversibility of smoke-induced changes.
Carcinogenicity of Deuterium-Labeled N-Nitroso-N-methylcyclohexylamine in Rats2
Authors: William Lijinsky, Melvin D. Reuber
Journal: JNCI Journal of the National Cancer Institute (1980)

F344 rats were treated with both unlabeled N-nitroso-N-methylcyclohexylamine (NMC) and deuterium-labeled NMC (NMC-d3) in the methyl group. Both compounds were administered in the drinking water at concentrations of 50 and 12.5 mg/liter. The NMC-d3 was not less carcinogenic than the unlabeled NMC, which suggested that oxidation of the methyl group is not a rate-limiting step in the induction of esophageal tumors.
Tight junction proteins claudin 3 and 4 in bronchioles and bronchi of COPD and effect of cigarette smoke, slug and twist in vivo and in vitro
Authors: Heta Merikallio, Ylermi Soini, Aki Manninen, Paavo Pääkkö, Siri Lehtonen, Riitta Kaarteenaho, Terttu Harju
Journal: European Respiratory Journal (2013)

Tight junctions (TJ) form a barrier in airway epithelial cells against the exogenous compounds to prevent their access into lung tissue. Cigarette smoke exposure damages epithelial barrier function possibly by promoting TJ disassembly. It is not yet known how this phenomenon is involved in COPD pathogenesis.  The aim of this study was to investigate changes in the expression of selected tight junction proteins (claudin 3 and 4) and transcription factors (slug and twist) in bronchiole and bronchi of non-smokers, smokers and COPD-patients in vivo by immunohistochemistry. The effects of cigarette-smoke extract exposure and twist or slug knockdown (KD) on levels of claudin 3 and 4 mRNA expression and transepithelial resistance (TER) were investigated by using BEAS-2B cells.  Claudin 3 and 4 were increased in bronchioles of smokers and COPD with an association of pack-years. Claudin 3 was also enhanced in bronchi in COPD. Transcription factors were inversely associated with claudin expressions in bronchioles and bronchi. In vitro, the expression of mRNA of both studied claudins were upregulated in slug and twist KD cells. Cigarette smoke-extract up-regulated the expressions of claudin 4 in BEAS-2B cells and claudin 3 in slug KD cells, but did not have any major effect in twist KD cells. The TER was higher in twist KD cells than in BEAS-2B cells.  In conclusion, claudin 3 and 4 were differently expressed in bronchioles and bronchus of smokers and COPD patients suggesting that the variable changes of TJ proteins may have a role in the pathogenesis of COPD. In vitro, cigarette smoke as well as slug and twist seemed to regulate expression of claudin mRNA.
Abstract 16263: Role for {beta}3-Receptor Activation in ATP-Mediated Endothelial Nitric Oxide Release
Authors: R. P Mason, Robert F Jacob, Adam M Jacoby, Roman Kaliszan, J. J Corbalan, Tadeusz Malinski
Journal: Circulation (2011)

Background: Endothelial-dependent nitric oxide (NO) release regulates vasodilation and slows atherogenesis. Cellular ATP has been shown to stimulate NO release through an autocrine pathway involvin...
The effect of dose on the antimalarial efficacy of artemether–lumefantrine: a systematic review and pooled analysis of individual patient data
Authors: NM Anstey, RN Price, Tme Davis, HA Karunajeewa, I Mueller, U D'Alessandro, A Massougbodji, F Nikiema, JB Ouedraogo, H Tinto, I Zongo, A Same-Ekobo, M Kone, H Menan, AO Toure, W Yavo, PE Kofoed, BH Alemayehu, D Jima, E Baudin, E Espie, C Nabasumba, L Pinoges, B Schramm, M Cot, P Deloron, JF Faucher, JP Guthmann, B Lell, S Borrmann, GO Adjei, J Ursing, E Tjitra, K Marsh, J Peshu, E Juma, BR Ogutu, SA Omar, P Sawa, AO Talisuna, M Khanthavong, M Mayxay, PN Newton, P Piola, AA Djimde, OK Doumbo, B Fofana, I Sagara, Q Bassat, R Gonzalez, C Menendez, F Smithuis, T Bousema, PA Kager, PF Mens, Hdfh Schallig, I van Den Broek, M van Vugt, ML Ibrahim, CO Falade, M Meremikwu, JP Gil, C Karema, Ba, B Faye, O Faye, O Gaye, JL Ndiaye, M Pene, D Sow, K Sylla, Rck Tine, LK Penali, KI Barnes, LJ Workman, A Lima, I Adam, NB Gadalla, Efm Malik, A Bjorkman, A Martensson, BE Ngasala, L Rombo, P Aliu, S Duparc, S Filler, B Genton, EM Hodel, P Olliaro, S Abdulla, E Kamugisha, Z Premji, SA Shekalaghe, EA Ashley, VI Carrara, R McGready, F Nosten, AM Faiz, SJ Lee, NJ White, AM Dondorp, JJ Smith, J Tarning, J Achan, H Bukirwa, A Yeka, E Arinaitwe, SG Staedke, Kamya, F Kironde, CJ Drakeley, M Oguike, CJ Sutherland, F Checchi, P Dahal, JA Flegg, PJ Guerin, C Moreira, C Nsanzabana, CH Sibley, K Stepniewska, PW Gething, Si Hay, B Greenwood, SA Ward, PA Winstanley, G Dorsey, B Greenhouse, PJ Rosenthal, A Grivoyannis, K Hamed, J Hwang, PS Kachur, M Nambozi
Journal: The Lancet Infectious Diseases (2015)
Circadian rhythms of melatonin, cortisol and cytokines in pediatric obstructive sleep apnea syndrome
Authors: Valentina Milan, Michela Gaiazzi, Antonella Luce, Ramona Maio, Franca Marino, Marco Cosentino, Luana Nosetti, Luigi Nespoli
Journal: European Respiratory Journal (2011)

Introduction:  Several neuroimmunological mediators exhibit a circadian organization. Melatonin, cortisol and somnogenic cytokines can be altered in conditions of disturbed sleep.   Aims and objectives:  The aim of the research is to investigate whether melatonin, cortisol, Tumor Necrosis Factor-α (TNF-α) and Interleukin-1β (IL-1β) show altered circadian rhythms in pediatric Obstructive Sleep Apnea (OSAS).   Methods:  47 children (26 OSAS, 21 not OSAS) underwent a nocturnal polysomnography and 2 blood samples were taken (2.00 am and 8.00 am). Cortisol and melatonin plasma concentrations were assayed using a radioimmunoassay technique. Cytokines were dosed from the supernatant of a 24-hours cell culture system (ELISA) in basal condition and after stimulation with phytohemagglutinin (PHA).   Results:  The circadian organization of cortisol and melatonin was not altered in OSAS. In fact pediatric OSAS is not associated with an important sleep fragmentation that could affect circadian rhythms of hormones. Circadian rhythms of TNF-α and IL-1β had lost the nocturnal physiological peak and an additional early morning peak had developed (TNF-α: P   Conclusions:  The interaction among sleep regulation, circadian rhythms, inflammation, immunomodulation and hormone release is an interesting starting point for future research in this field.
VATS lung biopsy is the method of choice for patients with ambiguous pulmonary pathology to establish a morphologic diagnosis
Authors: Mikle Pikunov, Yury Esakov
Journal: European Respiratory Journal (2011)

Objectives:  In spite of intensive development of diagnostic tools in pulmonology such as HRCT, PET, bronchoscopic examination peripheral lung lesions (PLL) and interstitial lung diseases (ILD) are often require excision lung biopsy for the morphological diagnosis. We evaluate the efficiency and safety of the VATS lung biopsy in the final diagnosis for patients with pulmonary diseases.   Methods:  230 patients with PLL (group I) and 87 patients with ILD (group II) were enrolled. Mean age: 54±20 y. We used HRCT for lesion(s) visualization in all cases. All patients in both groups underwent VATS lung biopsy and morphological investigation of the specimens to establish a final diagnosis.   Results:  In accordance to preoperative examination in group I there were: neoplasm9s, tuberculomas and hamartomas. In the group II there were suspicions to sarcoidosis, idiopathic pulmonary fibrosis (IPF), alveolitis or lymphangioleyomiomatosis (LAM). Morphological diagnosis was obtained in all cases. We found benign neoplasm 39%, early forms of lung cancer in 42%, tuberculomas in 12%, metastatic disease 4,2%, carcinoid tumors in 2%, and nidal fibrosis in 5,6% of all specimens in group I. In the group II there were sarcoidosis (48%), IPF (26%), alveolitis (24%) and LAM (2%). Accuracy of preoperative examination was 91% and 86% in the first and second groups respectively.   Conclusion:  VATS lung biopsy provides adequate specimen volume for morphologic diagnosis and associated with 100% diagnostic accuracy. Minimal postoperative morbidity and mortality rates are justified this procedure as a method of choice for patients with ILD and PLD.
High-Dose Leucovorin as Sole Therapy for Methotrexate Toxicity
Authors: Carlos D. Flombaum, Paul A. Meyers
Journal: Journal of Clinical Oncology (1999)

Hemodialysis, hemoperfusion, thymidine, and carboxypeptidase have been recommended together with high-dose (HD) leucovorin (LV) to treat patients at risk for methotrexate (MTX) toxicity. To elucidate the efficacy of high LV rescue as the sole salvage modality for severe MTX intoxication, we studied 13 patients who were treated in this fashion at Memorial Sloan-Kettering Cancer Center (New York, NY).To identify patients at high risk for severe MTX toxicity, we performed a retrospective review of all patients with MTX levels greater than 100 micromol/L at 24 hours and greater than 10 micromol/L at 48 hours after HD MTX.A total of 13 patients were identified. The median MTX concentration was 164 micromol/L at 24 hours (range, 102 to 940 micromol/L), 16.3 micromol/L at 48 hours (range, 10.5 to 190 micromol/L), and 6.2 micromol/L at 72 hours (range, 1.35 to 39 micromol/L). MTX levels remained greater than 0.1 micromol/L for an average of 11 +/- 3 days (mean +/- SD) (range, 7 to 17 days). In addition to supportive treatment with hydration and sodium bicarbonate administration, all patients were treated solely with HD LV, which was started within the first 24 hours in nine patients, 48 hours in three patients, and 72 hours in one patient in doses that varied from 0.24 to 8 g/d. Significant neutropenia (neutrophil count < 1,000/ microL) occurred in eight patients and lasted for 1 to 5 days. Thrombocytopenia (platelet count < 100,000/microL) occurred in seven patients and lasted for 5 to 10 days. Other toxic manifestations included mucositis of varying degrees, diarrhea, and neutropenic fever, but all patients recovered.In the range of MTX levels observed, HD LV can be used as a sole therapy for MTX toxicity without the need for extracorporeal removal and with tolerable morbidity.
Efficacy of roflumilast in the frequent exacerbation COPD phenotype
Authors: Jadwiga Wedzicha, Klaus Rabe, Peter Calverley, Fernando Martinez, Dirk Bredenbröker, Manja Brose, Udo-Michael Goehring
Journal: European Respiratory Journal (2011)

Background:  COPD exacerbations (EXs) are associated with increased morbidity, mortality and disease progression. The ECLIPSE study showed the best predictor of future EXs is a history of EXs, identifying a frequent exacerbator phenotype maintained over time. Roflumilast (ROF) reduces EX rate in frequent exacerbators, but its relative effect in this phenotype is not known.   Methods:  In a post-hoc pooled analysis of two 1-yr studies of ROF 500μg in pts with severe COPD, chronic bronchitis and a history of EXs, pts were classified as frequent (≥2 events) or infrequent (1 event) exacerbators based on moderate/severe EX history in the previous yr. EX frequency status was analysed in ROF- and placebo (PBO)-treated pts at baseline and at yr 1.   Results:  Among ROF-treated frequent exacerbators (n=413), 32.0% still had frequent EXs at yr 1 vs 40.8% of PBO-treated pts (n=417; RR=0.799, p=0.0148). Among infrequent exacerbators, 17.5% of ROF-treated pts (n=1124) had ≥2 EXs at yr 1 vs 22.9% of PBO-treated pts (n=1137; RR=0.768, p=0.0018). This reduction was similar when considering concomitant LABA, previous ICS treatment or severe EXs leading to hospitalisation/death. When analysed by COPD severity, 26.4% of ROF-treated frequent exacerbators with severe COPD (FEV 1  30–50% predicted, n=246) still had frequent EXs at yr 1 vs 38.9% of PBO-treated pts (n=239; RR=0.683, p=0.0042); the percentage of frequent exacerbators was similar between treatments in pts with very severe COPD (FEV 1     Conclusions:  This analysis shows that ROF shifts pts from the frequent to the more stable infrequent exacerbator state. This effect was not seen in frequent exacerbators with very severe COPD, highlighting the need for early treatment initiation.
Association of vitamin D deficiency with severity of acute respiratory infection: A case-control study in New Zealand children
Authors: Tristram R. Ingham, Bernadette Jones, Carlos A. Camargo, Joanna Kirman, Anthony C. Dowell, Julian Crane, Thorsten V. Stanley, Keith Grimwood
Journal: European Respiratory Journal (2014)

Background:    Acute respiratory infections (ARI) are a major source of childhood morbidity and excess winter hospitalisations. Vitamin D modulates innate immunity with recent associations demonstrated between vitamin D deficiency and several respiratory illnesses.    Objective:    We evaluate the association of blood 25(OH)D 3  with ARI severity in early childhood, hypothesising that children hospitalised with ARI have lower levels of vitamin D.    Methods:    We conducted an unmatched case-control study of children aged  3  was collected by finger or heel prick as dried blood spots and analysed by LC-MS/MS.    Results:    25(OH)D 3  was obtained in 469 children (227 cases, 242 controls) with levels (median, interquartile range) of 48 (24-65) nmol/L among cases and 52 (31-67) nmol/L among controls. Only 74 (16%) children had levels ≥75nmol/L. 60 (26%) cases and 42 (17%) controls were deficient (25(OH)D 3  levels     Conclusion:    Vitamin D deficiency was more frequent among children hospitalized for ARI, as compared to those with outpatient ARI. Vitamin D status may contribute to ARI severity amongst NZ children.