tbuckley/cabot-search huggingface dataset:
Intensive combination chemotherapy, concurrent chest irradiation, and warfarin for the treatment of limited-disease small-cell lung cancer: a Cancer and Leukemia Group B pilot study.
Authors: J Aisner, M Goutsou, L H Maurer, R Cooper, P Chahinian, R Carey, A Skarin, R Slawson, M C Perry, M R Green
Journal: Journal of Clinical Oncology (1992)

In prior Cancer and Leukemia Group B (CALGB) studies, combined chemotherapy and thoracic irradiation was superior to chemotherapy alone in limited-disease (LD) small-cell lung cancer (SCLC). A combined modality pilot study was performed to test the feasibility of adding warfarin to aggressive chemoradiotherapy for LD SCLC.Combination chemotherapy with doxorubicin 45 mg/m2 intravenously (IV) on day 1, cyclophosphamide 800 mg/m2 IV on day 1, and etoposide (ACE) 80 mg/m2 on days 1 to 3 was given every 21 days for the first three courses. The fourth and fifth courses substituted cisplatin 33 mg/m2 IV on days 1 to 3 for the doxorubicin, with concurrent chest irradiation to a total of 4,000 cGy given in 20 fractions during a 4-week period followed by a boost of 1,000 cGy in five fractions during a 1-week period. Prophylactic cranial irradiation, 3,000 cGy was given concurrently in 10 fractions during a 2-week period. Courses 6 to 8 again used ACE chemotherapy, but courses 4 to 8 were given on a 28-day schedule with dose adjustment for hematologic or renal toxicity. Warfarin was given throughout the treatment period titrated to achieve a prothrombin time (PT) of 1.5 to 2 times the control. Patients with histologically proven limited-stage SCLC, good performance status, and normal renal, hematologic, and hepatic functions were eligible.Sixty-one of 66 patients entered onto the study were eligible and assessable. Fifty-four (89%) (95%) confidence interval [CI], 78% to 95%) experienced an objective response, 35 (57%) achieved a complete response (CR) (95% CI, 44% to 70%), and 17 (28%) achieved a partial response (95% CI, 16% to 39%). Median durations were CR, 26.3 months; failure-free survival, 11.8 months; and survival, 18 months. Forty-one percent of the patients were alive at 2 years, 33% were alive at 3 years, and 25% were alive at 4 or more years. Median follow-up for survivors is 5 years (range, 3.5 to 5.9 years). Severe or life-threatening myelosuppression occurred in 90%, infection occurred in 34%, fever without documented infection occurred in 26%, and pulmonary toxicity occurred in 6%. Another 6% of patients experienced severe or life-threatening hemorrhages. There were four treatment-related fatalities. The pulmonary toxicities have been associated with the resumption of ACE chemotherapy after chest irradiation.These highly encouraging response and survival results compare favorably with any prior CALGB group study. Although they are somewhat more toxic, they are comparable to the best published results. A randomized study that examines the role of warfarin is underway.
A CXCR2 antagonist inhibits polyI:C-induced airway neutrophil, but not lymphocyte infiltrate
Authors: Paul Harris, Ruoqi Peng, Lisa Burns, Jonathan E. Phillips, Jay S. Fine, Christopher S. Stevenson
Journal: European Respiratory Journal (2011)

Introduction: PolyI:C is a synthetic dsRNA that triggers an innate immune response through the activation of TLR3 and RNA helicases. Our aim was to dissect the mechanism driving polyI:C-induced airway neutrophilia.

Methods: Male, BALB/c mice were intranasally administered polyI:C (30 mg/animal) or saline under isofluorane. Bronchoalveolar lavage fluid (BALF) was collected 2-168h later (n=8). BALF cells were counted and inflammatory mediators were measured in BALF supernatants by ELISA. The efficacy of a CXCR2 antagonist, SCH563750 (3-30 mg/kg) or its vehicle (2% Klucel, 0.1% Tween 80 in water), was assessed by administering p.o. 1h prior to polyI:C challenge. Airway hyper-responsiveness (AHR) and BALF inflammation were assessed 24h later.

Results: Administration of polyI:C increased several mediators in the BALF. Greatest amongst these was KC, peaking at 2h (2366±397 in polyI:C vs 8±1 control animals; P<0.01) and remaining elevated up to 72h. Neutrophil infiltration followed the increased KC levels, increasing from 6h before resolving back to baseline at 96h. Lymphocytes, predominantly CD49b+ NK cells, increased from 24h and were still elevated 168h post-challenge. SCH563750 attenuated the neutrophils in the BALF by 92% at a dose of 30 mg/kg (P<0.01). SCH563750 had no effect on BALF lymphocytes or AHR, although there was a trend towards a reversal of the latter.

Conclusion: Poly I:C administration to the airways increased chemokine levels, including KC. The influx of neutrophils was abrogated by a CXCR2 inhibitor. The lack of neutrophil infiltrate did not affect lymphocyte migration to the airways, suggesting an independent mechanism drives this response.
Bronchoscopy and esophageal cancer
Authors: Alexandra Carreiro, Jorge Dionísio, Dina Matias, Teresa Almodovar, José Duro da Costa
Journal: European Respiratory Journal (2013)

Introduction  Bronchoscopy (BC) is essential in staging esophageal cancer (EC).   Aims  Evaluate the usefulness of BC in the preoperative staging of EC and its impact on therapeutic approach. Report our experience with bronchoscopic treatment in patients with EC. Compare the current results with those of our previous review (1990-1998).   Methods  Retrospective analyses of 449 bronchoscopies in 217 consecutive with EC patients between 2010-2012. Bronchoscopic findings were graded according to Choi-Baisi classification.   Results  72 patients had bronchoscopic abnormalities (Iia 13,4%; Iib 7,4%; III 12,4%). Main locations were trachea (72,2%) and left main bronchus (34,7%). Stage was changed in 23%, therapeutic approach in 18,4% and exclusion from surgery in 14,3% patients due to bronchoscopic results. No airway infiltration was found on resected specimens in all the 43 patients submitted to esophagectomy. Bronchoscopic and CT scan results were discordant in 30% patients. Bronchoscopic treatment (stent, electrocautery, silver nitrate) was performed in 24 patients (15 with obstruction due to extrinsic compression and tumor infiltration and 9 with esophagotracheal fistula). Respiratory symptoms improved in all. Comparing the results with our previous series, main differences were: more patients now undergo BC (72,3 vs 33,9 per year), with less endobronchial alterations (33,2% vs 57,7%), but more patients underwent bronchoscopic treatment (8 vs 5,7 per year).   Conclusion  All patients with newly diagnosed EC should undergo a BC for staging and therapeutic planning. Nowadays earlier referral allows for longer survival that leads to late complications for which BC still permits adequate palliation.
Effects of methoxypoly (Ethylene glycol) mediated immunocamouflage on leukocyte surface marker detection, cell conjugation, activation and alloproliferation
Authors: Dana L. Kyluik-Price, Mark D. Scott
Journal: Biomaterials (2015)

Tissue rejection occurs subsequent to the recognition of foreign antigens via receptor-ligand contacts between APC (antigen presenting cells) and T cells, resulting in initialization of signaling cascades and T cell proliferation. Bioengineering of donor cells by the covalent attachment of methoxypolyethylene glycol (mPEG) to membrane proteins (PEGylation) provides a novel means to attenuate these interactions consequent to mPEG-induced charge and steric camouflage. While previous studies demonstrated that polymer-mediated immunocamouflage decreased immune recognition both in vitro and in vivo, these studies monitored late events in immune recognition and activation such as T cell proliferation. Consequently little information has been provided concerning the early cellular events governing this response. Therefore, the effect of PEGylation was assessed by examining initial cell–cell interactions, changes to activation pathways, and apoptosis to understand the role that each may play in the decreased proliferative response observed in modified cells during the course of a mixed lymphocyte reaction (MLR). The mPEG-modified T cells resulted in significant immunocamouflage of lymphocyte surface proteins and decreased interactions with APC. Furthermore, mPEG-MLR exhibited decreased NFκB pathway activation, while exhibiting no significant differences in degree of cell death compared to the control MLR. These results suggest that PEGylation may prevent the direct recognition of foreign alloantigens by decreasing the stability and duration of initial cell–cell interactions.
Feasibility study of combining metronidazole with chemotherapy.
Authors: D J Stewart, J A Maroun, V Young, A F Crook, H S Hopkins, R C Yan, M T Richard, H Hugenholtz, R Bélanger, R Heringer
Journal: Journal of Clinical Oncology (1983)

Metronidazole, 1.5 g/sq m, was administered p.o. to patients with advanced malignancies 12 hr and 1 hr before and 6 hr and 24 hr after each of adriamycin, BCNU, and mitomycin-C. Doses of adriamycin varied from 50 to 90 mg/sq m. At an adriamycin dose of 75 mg/sq m, the median granulocyte nadir was 900/microliters and the median platelet nadir was 240,000/microliters. No enhancement of stomatitis or cardiotoxicity was noted at the doses studied. Doses of BCNU varied from 145 to 265 mg/sq m. At a BCNU dose of 240 mg/sq m, the median granulocyte nadir was 2600/microliters and the median platelet nadir was 102,000/microliters. Two patients developed hypotension that may have been due to a metronidazole-alcohol interaction. Doses of mitomycin-C varied from 10 to 20 mg/sq m. At a mitomycin-C dose of 20 mg/sq m, the median granulocyte nadir was 1300/microliters and the median platelet nadir was 81,000/microliters. Four of 40 patients developed pulmonary toxicity and one developed renal toxicity. Of 11 evaluable patients treated on the adriamycin regimen, 4 responded and 5 stabilized. With BCNU, 7 of 17 responded and 2 stabilized. With mitomycin-C, 2 of 32 responded and 12 stabilized. Overall, 4 of 8 patients with squamous cell carcinoma or adenocarcinoma of the lung attained partial remissions and one had a minor response. Using this metronidazole dose schedule, phase II studies are being conducted with adriamycin, 75 mg/sq m, in squamous cell and adenocarcinomas of the head and neck; with BCNU, 240 mg/sq m, in glioblastomas and squamous cell and adenocarcinoma of the lung; and with mitomycin-C, 20 mg/sq m, in adenocarcinomas of the breast and colon.
Full description of controls is needed in study
Authors: P. Sasieni
Journal: BMJ (1996)

EDITOR,—It is not uncommon to select controls from two sources because of concerns about the suitability of any one source. Superficial analysis of the data presented by Michael A Lewis and colleagues shows that hospital controls who use oral contraceptives are roughly three times less likely than community controls to use third generation pills (table 1).1 Naively, one might conclude that third generation pills are a general tonic, particularly in comparison with second generation pills: women who use them are …
The airways response to inhaled corticosteroid therapy in children with asthma exposed to environmental tobacco smoke
Authors: Snezana Radic, Zorica Zivkovic, Branislav Gvozdenovic, Sofija Cerovic, Olivera Calovic, Tamara Krivokapic, Milka Micic-Stanojevic, Olivera Vlahovic, Vera Aleksic
Journal: European Respiratory Journal (2013)

Background: Corticosteroids are the most effective anti-inflammatory therapy for asthma. A reduction in histone deacetylase (HDAC) activity is suggested to prevent the anti-inflammatory action of inhaled corticosteroids (IC). Cigarette smoke is known to reduce HDAC expression.  Aim: To compare the lung function test parameters and the response to the IC in the asthmatic children exposed and not exposed to environmental tobacco smoke (ETS).  Methodology: 527 children (6-16 years) with moderate to severe asthma performed spirometry before and after the 6 months of IC. According to questionnaire, we divided children into two groups: ETS exposed (ETSE, N 337) and ETS free (ETSF, N 190).  Results: There were 49.9% of boys and 50.1% of girls (mean age 10.83). Average dose of Fluticasone dipropionate (FP) was 225.11±119.98 mcg per day per child. Among ETSE children, 208 were with one, 129 with both smoking parents, 228 had smoking mother and 238 had smoking father. ETSE children received statistically higher dose of FP, and dose of FP increased with increasing of number of smokers in the family (F=45.412, p  Conclusion: ETS impaired the lung function growing rate in exposed children with asthma, but did not decrease response to inhaled corticosteroids. It is necessary to educate smoking parents to protect asthmatic children from tobacco smoke negative influence.
World‐wide relative contribution of hepatitis B and C viruses in hepatocellular carcinoma
Authors: Catherine de Martel, Delphine Maucort‐Boulch, Martyn Plummer, Silvia Franceschi
Journal: Hepatology (2015)

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major causes of hepatocellular carcinoma (HCC). In order to assess the relative contribution of HBV and HCV to HCC worldwide, and identify changes over time, we conducted a systematic review of case series published up to the year 2014. Eligible studies had to report seroprevalence of both hepatitis B surface antigen (HBsAg) and antibodies to HCV (anti‐HCV), alone and in combination, for at least 20 adult HCC cases. Studies using a first‐generation enzyme‐linked immunosorbent assay test for HCV were excluded. A total of 119,000 HCC cases in 260 studies were included from 50 countries. Most European and American countries show a preponderance of HCV over HBV and a substantial fraction of viral marker–negative cases. Asian and African countries generally show a predominance of HBV. The fraction of HCV‐positive HCC cases is substantial in Taiwan, Mongolia, Japan, and Pakistan as well as in Western‐Central Asia and Northern Africa. No eligible studies were available in Oceania, large parts of Africa, Eastern Europe, and Central Asia. The United States, Brazil, and Germany show evidence of higher prevalence of HCV in HCC since the year 2000. Conversely, Japan and Italy show a decline in the proportion of HCV‐positive HCC. Conclusion : HBV and HCV are predominant causes of HCC in virtually all world areas, with a growing fraction of HCC cases in several countries attributable to HCV. (H epatology 2015;62:1190‐1200)
Feasibility of Outpatient 24-Hour Closed-Loop Insulin Delivery
Authors: Martin I. de Bock, Anirban Roy, Matthew N. Cooper, Julie A. Dart, Carolyn L. Berthold, Adam J. Retterath, Kate E. Freeman, Benyamin Grosman, Natalie Kurtz, Fran Kaufman, Timothy W. Jones, Elizabeth A. Davis
Journal: Diabetes Care (2015)

Studies using outpatient closed-loop insulin delivery for type 1 diabetes have recently been published (1–5). We conducted a 5-day outpatient feasibility study comparing hybrid closed-loop (HCL) to sensor-augmented pump therapy with low-glucose suspend (SAPT + LGS) in eight patients with type 1 diabetes using an open-label randomized crossover trial design (ACTRN12614001005640). We used the Medtronic HCL system: MiniMed insulin pump, MiniMed Enlite II glucose sensor, MiniMed MiniLink REAL-time sensor, MiniMed Translator, and an Android mobile device with the algorithm (proportional integrative derivate with insulin feedback and additional safety parameters—primarily being an upper limit of allowable insulin delivery). Multiple algorithm parameters were individualized according to total daily insulin requirements in the preceding 48 h. Meals were announced by entering a capillary glucose value and meal carbohydrate content, for which bolus insulin was delivered according to the patient’s unique carbohydrate ratio. The Android mobile device sent data via the Internet, …
IGRA testing correlation with clinical and laboratory parameters in patients with tuberculosis
Authors: Jana Kotrbova, Martina Vasakova, Jiri Homolka, Emilia Kopecka, Jelena Skibova
Journal: European Respiratory Journal (2011)

Background:  IGRA test (Quantiferon-TB-Gold in-tube test, further referred to as QFT) is based on ELISA method for interferon gamma evaluation created by antigen specific T-lymfocytes. QFT has become a part of complex tuberculosis diagnosis.   Aims and objectives:  QFT outcomes comparison with other diagnostic methods in patients with tuberculosis and assessment of malnutrition and immunity system influence on QFT outcomes.   Methods:  In a group of 62 patients treated in our clinic for tuberculosis in 2010, we compared the QFT results with tuberculin skin test (TST), PCR, smear and culture. The effect of malnutrition and lymfopenia on possible false QFT negativity was studied as well. Non-parametric Mann-Whitney rank test was used for comparing the mean TST value with QFT and in other parameters, Chi-square test was used in frequency tables.   Results:  Statistically significant correlation between QFT positivity and TST magnitude, PCR positivity and culture positivity was demonstrated. Statistical significance has not been proven neither between QFT outcomes and microscopic diagnosis nor the effect of malnutrition or lymfopenia on possible false QFT negativity was proven.
Adjuvant chemotherapy with and without tamoxifen in the treatment of primary breast cancer: 5-year results from the National Surgical Adjuvant Breast and Bowel Project Trial.
Authors: B Fisher, C Redmond, A Brown, E R Fisher, N Wolmark, D Bowman, D Plotkin, J Wolter, R Bornstein, S Legault-Poisson
Journal: Journal of Clinical Oncology (1986)

In this National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial, 1,891 women with primary operable breast cancer and positive axillary nodes were randomized between Jan, 1977 and May 1980 to receive L-phenylalanine mustard (L-PAM) and 5-fluorouracil (5-FU) either with or without tamoxifen (TAM)-PFT. This report presents life table probabilities, cumulative odds ratios, and P values for disease-free survival (DFS) and survival at yearly intervals through 5 years of observation (mean time on study, 72 months). When patients were examined overall without regard for any discriminant associated with outcome, ie, age, number of positive nodes, or tumor receptor status, there was a significant prolongation of DFS (P = .002), but not survival through the fifth postoperative year. The benefit was almost entirely restricted to those greater than or equal to 50 years with greater than or equal to 4 positive nodes. In that group there was a 66% greater chance of remaining disease free if PFT was received (P less than .001), and there was also a significant survival benefit (P = .02). The advantage from PFT was found to be associated with tumor estrogen receptor (ER) and progesterone receptor (PR) as well as patient age and nodal status. Overall there was a significant improvement in DFS from PFT in those having tumors with an ER or PR level greater than or equal to 10 femtomole (fmol) (P = .01 and .009, respectively). No significant benefit in DFS or survival has been observed in patients less than or equal to 49 years old related either to nodes or tumor receptor status. Survival continues to be adversely affected by TAM in those patients (less than or equal to 49 years old), particularly when their tumors have a PR of 0 to 9 fmol (P = .007). In patients greater than or equal to 50 years old with four or more positive nodes, a significant DFS benefit persisted through the fifth year of observation in those having tumor ER or PR levels greater than 10 fmol (P less than .001 and .002). The advantage was observed in patients 50 to 59 years old as well as those 60 to 70. Women in the older decade demonstrated some advantage from PFT when their tumor ER or PR was 0 to 9 fmol. The most likely explanation for this finding is analytical error in receptor analyses.(ABSTRACT TRUNCATED AT 400 WORDS)
Effects of eltrombopag on platelet count and platelet activation in Wiskott-Aldrich syndrome/X-linked thrombocytopenia
Authors: Anja J. Gerrits, Emily A. Leven, Andrew L. Frelinger, Sophie L. Brigstocke, Michelle A. Berny-Lang, W. Beau Mitchell, Shoshana Revel-Vilk, Hannah Tamary, Sabrina L. Carmichael, Marc R. Barnard, Alan D. Michelson, James B. Bussel
Journal: Blood (2015)
Patterning of Fibroblast and Matrix Anisotropy within 3D Confinement is Driven by the Cytoskeleton
Authors: Janna V. Serbo, Scot Kuo, Shawna Lewis, Matthew Lehmann, Jiuru Li, David H. Gracias, Lewis H. Romer
Journal: Advanced Healthcare Materials (2015)

Effects of 3D confinement on cellular growth and matrix assembly are important in tissue engineering, developmental biology, and regenerative medicine. Polydimethylsiloxane wells with varying anisotropy are microfabicated using soft‐lithography. Microcontact printing of bovine serum albumin is used to block cell adhesion to surfaces between wells. The orientations of fibroblast stress fibers, microtubules, and fibronectin fibrils are examined 1 day after cell seeding using laser scanning confocal microscopy, and anisotropy is quantified using a custom autocorrelation analysis. Actin, microtubules, and fibronectin exhibit higher anisotropy coefficients for cells grown in rectangular wells with aspect ratios of 1:4 and 1:8, as compared to those in wells with lower aspect ratios or in square wells. The effects of disabling individual cytoskeletal components on fibroblast responses to anisotropy are then tested by applying actin or microtubule polymerization inhibitors, Rho kinase inhibitor, or by siRNA‐mediated knockdown of AXL or cofilin‐1. Latrunculin A decreases cytoskeletal and matrix anisotropy, nocodazole ablates both, and Y27632 mutes cellular polarity while decreasing matrix anisotropy. AXL siRNA knockdown has little effect, as does siRNA knockdown of cofilin‐1. These data identify several specific cytoskeletal strategies as targets for the manipulation of anisotropy in 3D tissue constructs.
Nasal symptoms and doctor-diagnosed chronic lung diseases
Authors: Lucia Cazzoletti, Marcello Ferrari, Mario Olivieri, Giuseppe Verlato, Pierpaolo Marchetti, Leonardo Antonicelli, Roberto Bono, Maria Grazia Panico, Pietro Pirina, Simona Villani, Roberto de Marco
Journal: European Respiratory Journal (2013)

Although there is evidence of nasal involvement in chronic pulmonary diseases, few studies have been conducted in southern Europe on population samples of wide age-class range. We aimed at estimating the self-reported prevalence of allergic rhinitis (AR) and non-allergic rhinitis (NAR) according to age and to the presence of self-reported doctor-diagnosed asthma and COPD.

A screening questionnaire was administered to random samples of the general Italian population \[20-44 (n=5163), 45-64 (n=2167), 65-84 (n=1030) yrs\] (Gene Environment Interactions in Respiratory Diseases -GEIRD- study, response rates: 53%, 62% and 52%, in the 3 age groups, respectively). The prevalence of AR and of NAR was modeled by means of a logistic model, adjusting for season, percentile rank of cumulative response, centre, type of survey (postal/phone).

NAR showed a significant descending pattern in females from 18.4% [IC95%:16.9,19.9] in 20-44 yrs age class, to 14.1% [10.5,17.7] in 65-84 yrs age class (p=0.0095), and a non-significant ascending pattern in males from 16.4% [14.9,18.0] to 19.9% [16.2,23.6]. AR decreases from 25.7% [24.5,27.0] in 20-44 yrs age class to 20.2% [18.4,21.9] and 14.6% [12.2,17.0] in 45-64 and 65-84 yrs age class respectively (p<0.0001), without gender difference. AR was significantly associated with both asthma [OR 6.5; IC95%:5.4,7.8] and COPD [OR 1.4; 1.1,1.8], while NAR was associated only with COPD [OR 2.4; 1.9,3.0].

AR and NAR prevalence is very high in the general population; AR is associated with asthma and COPD and shows a negative relationship with age, without gender difference; NAR is associated only with COPD, with prevalence equally distributed in all age-classes in men, and negatively associated to age in women.