tbuckley/cabot-search huggingface dataset:
LSC 2014 abstract - Targeting of microRNAs can restore innate anti-viral response in asthma
Authors: Hitasha Rupani, Patrick Dennison, Nivenka Jayasekera, Laurie Lau, Tilman Sanchez-Elsner, Peter Howarth
Journal: European Respiratory Journal (2014)

Virus-induced disease exacerbation is common in asthma and studies have shown that alveolar macrophages (AM) from asthmatics have reduced interferon (IFN) responses to rhinovirus (RV) infection. The mechanism behind this defect is unclear. We hypothesised that this deficiency is caused by a defect in the toll-like receptor (TLR) 7 pathway and is driven by aberrations in microRNA (miR) expression in AM. We identified and focused on 3 miRs predicted to target TLR7. We also hypothesised that manipulating the expression of these miRs could restore the defective IFN response in asthmatic AM.

AM were isolated from bronchoalveolar lavage from healthy (HC) and severe asthma (SA) subjects. Expression of miRs and TLR7 was determined by qRT-PCR and western blotting. A TLR7-luciferase reporter construct was generated to confirm the bioinformatics predictions. AM were transfected with anti-miRs directed against the 3 miRs and treated with imiquimod (5ug/ml), a TLR7 agonist, or RV16. IFN (a and β) expression was determined after 24 hours using qRT-PCR and ELISA.

Expression of miRs-150, -152 and -375 was increased and expression of TLR7 reduced in SA AM compared to HC. Using the TLR7-luciferase reporter construct we showed that the 3 miRs directly targeted the 3'UTR of TLR7. Compared to mock transfected AM, AM transfected with the 3 anti-miRs showed increased imiquimod and RV16-induced IFN expression.

Reduced expression of TLR7 in SA AM is related to increased expression of miRs-150, -152 and -375. We propose this leads to impaired viral sensing by asthmatic AM and defective IFN response to RV. Knock-down of these miRs in AM rescues the expression of IFN, providing a novel target for therapy in asthma.
Asthma and asthma-like symptoms in Greece. The Greece asthma national prevalence survey
Authors: Eleftherios Zervas, Stelios Loukides, Konstantinos Kostikas, Petros Bakakaos, Eleni Tzortzaki, Mina Gaga
Journal: European Respiratory Journal (2012)

Background Asthma is a major health problem world-wide. Prevalence surveys of asthma provide valid information and help design national programs of health care services. Recent data are missing from Greece.  Objectives To study the prevalence of asthma and associated symptoms in the adult population of Greece.  Methods A nation-wide, cross-sectional, community-based survey of asthma and asthma-like symptoms was conducted, using a pre-tested structured questionnaire based on the ECRHS Questionnaire for adults. A stratified random sampling method was used to select 2,191 participants, aged > 18 years old. Data was collected with face-to-face interviews.  Results The self-reported current prevalence of physician-diagnosed asthma and asthma-like symptoms were as follows: physician-diagnosed asthma 9 %, asthma attack 2.3%, use of asthma medication 3.7%, awakening from shortness of breath 22.3%, awakening from cough 24.1%, wheezing 19% and nasal allergies 23.3%. The incidence of asthma was calculated as 16 new cases per thousand people. Smoking prevalence was high both in the general population and in asthmatics (39.2% and 36.4%, respectively). Asthma prevalence was higher in Athens (10.9%), while there was no difference between rural and urban areas (8.5% and 7.8%, respectively).  Conclusions The prevalence of asthma and associated symptoms in Greece is high, presenting a substantial increase from the last survey conducted 20 years ago. The results of this survey highlight the increasing social burden and impact of asthma in Greece and may aid policy makers and healthcare providers to plan effective health strategies for the proper diagnosis and management of this disease.
Surgical Relief of Obstructive Jaundice in a District General Hospital
Authors: M A R Al-Fallouji, R E C Collins
Journal: Journal of the Royal Society of Medicine (1985)

Fifty consecutive patients with obstructive jaundice treated by operation in Canterbury & Thanet Health District hospitals under the care of one surgeon (RECC) over a 6-year period have been studied. The pathology was found to be common bile duct (CBD) stone in 22 patients (44%); pancreatic carcinoma in 15 (30%), 3 of whom also had CBD stones; chronic pancreatitis in 4 (8%); extrahepatic CBD carcinoma in 4 (8%); ampulla of Vater carcinoma in 3 (6%); primary duodenal carcinoma in 1 (2%); and portahepatis obstruction in 4 (8%). The 8 postoperative deaths (16%) were found to be associated with high preoperative levels of serum bilirubin, but all occurred in patients with malignant disease. Complications occurred in 20 patients (40%) and bile culture state was found to be intimately related to the morbidity rather than operative mortality. The study represents a careful audit of the pathology distribution and the surgical management of obstructive jaundice as seen in district hospitals.
Immunopotentiation With BeG. I. Immune Response to Different Strains and Preparations2
Authors: G. B. Mackaness, D. J. Auclair, P. H. Lagrange
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Immunopotentiation With BeG. I. Immune Response to Different Strains and Preparations Get access G. B. Mackaness, G. B. Mackaness 3Trudeau Institute, Saranac Lake, N.Y. 12983 Search for other works by this author on: Oxford Academic PubMed Google Scholar D. J. Auclair, D. J. Auclair 3Trudeau Institute, Saranac Lake, N.Y. 12983 Search for other works by this author on: Oxford Academic PubMed Google Scholar P. H. Lagrange P. H. Lagrange 4Lilly International Fellow, Eli Lilly and Company, Indianapolis, Ind Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 5, November 1973, Pages 1655–1667, https://doi.org/10.1093/jnci/51.5.1655 Published: 01 November 1973 Article history Received: 29 May 1973 Accepted: 23 July 1973 Published: 01 November 1973
Effect of lifestyle factors on Staphylococcus aureus gut colonization in Swedish and Italian infants
Authors: E. Lindberg, I. Adlerberth, P. Matricardi, C. Bonanno, S. Tripodi, V. Panetta, B. Hesselmar, R. Saalman, N. Å berg, A.E. Wold
Journal: Clinical Microbiology and Infection (2010)
Influence of antibiotic resistance of pseudomonas aeruginosa on presenting features of community-acquired lower respiratory tract infections
Authors: Pavlina Nikolova, Yavor Ivanov, Plamen Pavlov, Tsania Popova, Elena Borissova, Petkana Hristova
Journal: European Respiratory Journal (2011)

Aim:  To evaluate the influence of resistant isolates of  Pseudomonas aeruginosa  on presenting features for patients with community-acquired lower respiratory tract infections (LRTIs).   Methods:  95 hospitalized patients (67 men, 28 women, average age 66,7±10,9y) with community acquired pneumonia (CAP), bronchiectasis and exacerbations of chronic obstructive pulmonary disease (COPD) and  Pseudomonas  aeruginosa  isolates were studied during a 5-year period. They were divided into two groups: with susceptible isolates, (n 1 =70, 73,7%, S group) and resistant to antibiotic testing, (n 2 =25, 26,3%, R group) and compared by sex, age, diagnosis, concomitant diseases, treatment, length of stay, outcome.   Results:  14,7% of the patients had CAP, 46,3% - bronchiectasis and 40% - COPD. Most of them had concomitant diseases – ishaemic heart disease: S/R - 62,4%/62% resp., diabetes - S/R -11%/12% resp. We found differences in: the change of antibiotic treatment according to the microbiological results (8%S/36%R, p 15 days - 3%S/12%R respectively, p   Conclusions:  The clinical features found in patients with resistant isolates of  P. aeruginosa  compared to susceptible ones were: more complications of the main disease, more frequent change of antibiotics during the course of treatment according to the microbiogical results and longer length of stay.
Anti-inflammatory and cytoprotective actions of the endogenous docosahexaenoic acid (DHA) electrophilic derivative 17-oxo-DHA
Authors: Chiara Cipollina, Stefania Gerbino, Serena Di Vincenzo, Rosalia Curto, Mark Gjomarkaj, Bruce A. Freeman, Francisco J. Schopfer, Elisabetta Pace
Journal: European Respiratory Journal (2012)

Inflammation of the airways is a hallmark of chronic obstructive pulmonary disease (COPD), one of the leading mortality cause worldwide. Bronchial epithelial cells and resident macrophages represent the first barrier in the lung against pathogens and external insults such as cigarette smoke, which is a major risk factor for COPD. Although the activation of the innate inflammatory response is required for defence purposes, uncontrolled activation, typical of COPD, leads to chronic inflammation causing tissue damage and enhanced risk of infection. Currently there is no therapy able to revert disease progression in COPD and therefore the search for new drugs is highly active.  Omega-3 derived electrophilic fatty acids have been recently discovered as endogenous anti-inflammatory molecules produced by activated macrophages by the action of cyclooxygenase-2.  In the present work, the anti-inflammatory and cytoprotective actions of the electrophilic DHA-derivative 17-oxo-DHA were evaluated in lipopolysaccharide-activated macrophages and in bronchial epithelial cells. We report that 17-oxo-DHA suppresses LPS-induced TNFalpha production in macrophages and increases intracellular glutathione and the expression of heme-oxygenase 1 in both cell types, thus providing protection against oxidative stress caused by cigarette smoke and inflammatory reactions.  Although the molecular mechanisms are still under investigation, overall the present results support a role for the electrophilic, omega-3 derived 17-oxo-DHA in limiting inflammatory reactions and modulating the antioxidant response, thus reducing cellular damage and promoting the resolution of inflammation.
Recruiting Minority Cancer Patients Into Cancer Clinical Trials: A Pilot Project Involving the Eastern Cooperative Oncology Group and the National Medical Association
Authors: Worta McCaskill-Stevens, Harlan Pinto, Alfred C. Marcus, Robert Comis, Randall Morgan, Kathy Plomer, Sarah Schoentgen
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Minority accrual onto clinical trials is of significant interest to cooperative oncology study groups. The Eastern Cooperative Oncology Group (ECOG) conducted a study to identify barriers and solutions to African American accrual onto clinical trials. METHODS: We hypothesize that the National Medical Association (NMA) might provide insight into ways to increase minority participation and that ECOG might facilitate that participation. Four sites were selected in which NMA chapters existed and ECOG main institutions with less than half of the corresponding percentage of minorities in their communities entered trials for 1992. Fifteen workshops were conducted using discussions and open-ended, self-administered questionnaires. RESULTS: Seventy percent of NMA physicians cited mistrust of the research centers, fear of losing patients, and a lack of respect from ECOG institutions as the most important barriers to minority cancer patient referrals, compared with 30% for ECOG physicians. Sixty-nine percent of NMA and 43% of ECOG physicians cited a lack of information about specific trials. Nearly half of NMA physicians (47%) cited a lack of minority investigators as a barrier, compared with 4% of ECOG physicians. Solutions by both groups were improved communication (73%) and culturally relevant educational materials (40%). ECOG physicians cited more minority outreach staff as a potential solution (22% v 6%). NMA physicians cited increased involvement of referring physicians (44% v 4%). CONCLUSION: NMA physicians who serve a significant sector of the African American population demonstrated a willingness to participate and work with a cooperative group effort to increase participation of minority patients and investigators.
Adherence with inhaled colistimethate sodium during a 6 month study in patients with non-cystic fibrosis bronchiectasis
Authors: Charles Haworth, Diana Bilton, Robert Kenyon
Journal: European Respiratory Journal (2013)

Adherence to inhaled medication treatment regimens is typically poor.  [1]  The I-neb AAD System is used by patients with cystic fibrosis (CF) for the aerosolised delivery of precise doses of colistimethate sodium (CMS; Promixin, Profile Pharma Ltd) and features routine recording of adherence data. We report on the adherence of patients enrolled in a pioneer, 6 month, multinational, double-blind, placebo-controlled study of the delivery of CMS via the I-neb AAD System to patients with non-CF bronchiectasis colonised by  Pseudomonas aeruginosa  [ISRCTN49790596]. Patients (n=144) were enrolled and randomised to twice daily CMS (1 MIU/mL) or placebo (0.45% saline), delivered using the I-neb AAD System (Table 1). Adherence data was examined at the end of the study.  Adherence exhibited by patients in both arms of the study was very high; 75% of patients demonstrated mean adherence of over 80% to their prescribed doses, and mean overall study adherence was 86%. This compares favourably with median nebuliser adherence of 36% in adult patients with CF.  [1]   1. Daniels T et al. Chest 2011;140;425-432.
Radiologic outcome among asymptomatic patients With upper lobe infiltrates With or Without treatment
Authors: May Uyking-Naranjo, Romulo Uy, Ronal Ciakaren
Journal: European Respiratory Journal (2013)

Background: There is a dilemma whether asymptomatic patients with upper lobe infiltrates should be treated with antibiotics or not. The outcome after administration of antibiotics to the asymptomatic groups of patients with upper lobe infiltrates has not been studied.

Objective: To determine if there will be radiologic resolution of upper lobe infiltrates in asymptomatic patients after 1 week antibiotic treatment in comparison with those not treated.

Study Design: Randomized Controlled Trial

Inclusion criteria: Age > 16 years; Chest Xray(CXR) of upper lobe infiltrates; asymptomatic patients; sputum AFB negative x 3 takes. Exclusion criteria: prior treatment with anti-kochs; antibiotics within the past 3 weeks. Participants were randomized into 2 groups using block randomization. Random numbers were electronically generated.

Outcome measures: CXR were repeated after 2 weeks for both groups. The CXR were read by 2 independent board certified radiologists.

Results: 78 participants were included in the study. 39 participants received 1 week antibiotic therapy while the rest did not receive treatment. The rate of resolution of infiltrates was 15.38% among those given treatment while 11.54% among those not given treatment. Based on the two proportion test analysis, this finding is statistically significant with a two-tailed p value of 0.0001.

Conclusion: Radiologic resolution of upper lobe infiltrates in asymptomatic patients was observed with or without antibiotic treatment. There is statistically significant difference in the rates of radiologic resolution of infiltrates among asymptomatic patients who were treated with antibiotics as compared to those who were not given treatment.
Phase III Randomized Study of Cisplatin Versus Paclitaxel Versus Cisplatin and Paclitaxel in Patients With Suboptimal Stage III or IV Ovarian Cancer: A Gynecologic Oncology Group Study
Authors: Franco M. Muggia, Patricia S. Braly, Mark F. Brady, Gregory Sutton, Theodore H. Niemann, Samuel L. Lentz, Ronald D. Alvarez, Paul R. Kucera, James M. Small
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To assess progression-free survival (PFS) and overall survival (OS) in patients with suboptimally debulked epithelial ovarian cancer receiving cisplatin (100 mg/m 2 ) or 24-hour infusion paclitaxel (200 mg/m 2 ) or the combination of paclitaxel (135 mg/m 2 ) followed by cisplatin (75 mg/m 2 ). PATIENTS AND METHODS: After stratification for disease measurability, patients were randomized to receive six cycles of one of the treatments every 3 weeks. If measurable, complete response (CR) or partial response (PR) was determined. RESULTS: Six hundred fourteen of 648 patients who entered onto the trial were eligible. Monotherapies were discontinued more frequently (cisplatin because of toxicity or patient refusal [17%], and paclitaxel because of progression [20%]) compared with the combination therapy (7% and 6%, respectively). Neutropenia, fever, and alopecia were more severe with paclitaxel-containing regimens; whereas anemia, thrombocytopenia, neurotoxicity, nephrotoxicity, and gastrointestinal toxicity were more severe with cisplatin-containing regimens. The CR/PR rates on paclitaxel monotherapy were significantly lower compared with the cisplatin regimens (42% v 67%, respectively; P &lt; .001). The relative hazard (RH) of first progression or death was significantly greater among those randomized to paclitaxel (RH = 1.41; 95% confidence interval [CI], 1.15 to 1.73; P &lt; .001) when compared with cisplatin; however, RH did not differ significantly between the two cisplatin regimens (RH = 1.06; 95% CI, 0.895 to 1.30). Relative to cisplatin, the death rate on paclitaxel was 15% greater (RH = 1.15; 95% CI, 0.929 to 1.42), and the death rate on the combination treatment was 1% less (RH = 0.99; 95% CI, 0.795 to 1.23). These differences among treatment groups were not statistically significant (P = .31). CONCLUSION: Cisplatin alone or in combination yielded superior response rates and PFS relative to paclitaxel. However, OS was similar in all three arms, and the combination therapy had a better toxicity profile. Therefore, the combination of cisplatin and paclitaxel remains the preferred initial treatment option.
New Developments in Thyroid Cancer
Authors: Robert I. Haddad
Journal: Journal of the National Comprehensive Cancer Network (2013)

Thyroid cancer is common but rarely deadly. Unfortunately, when the disease becomes refractory to radioactive iodine (RAI), few effective treatment options remain. This situation is changing, however, with the availability of multitargeted tyrosine kinase inhibitors. Cabozantanib and vandetanib, both recently FDA-approved for advanced or metastatic disease, have more than doubled progression-free survival in medullary thyroid cancer. New agents in the pipeline may yield even better outcomes, as discussed by Dr. Robert I. Haddad at the NCCN 18th Annual Conference.
Aqueous and vitreous penetration of levofloxacin after oral administration11The authors have no financial interest in levofloxacin or in any other product mentioned in this article.
Authors: Richard G Fiscella, Thao K.P Nguyen, Michael J Cwik, Brian A Phillpotts, Steven M Friedlander, Daniel C Alter, Michael J Shapiro, Norman P Blair, Jon P Gieser
Journal: Ophthalmology (1999)
A phase I study of the single-agent CDK4/6 inhibitor LEE011 in pts with advanced solid tumors and lymphomas.
Authors: Jeffrey R. Infante, Geoffrey Shapiro, Petronella Witteveen, John F. Gerecitano, Vincent Ribrag, Rashmi Chugh, Isra Issa, Abhijit Chakraborty, Alessandro Matano, Xumei Zhao, Sudha Parasuraman, Phillipe Cassier
Journal: Journal of Clinical Oncology (2014)

2528^ Background: LEE011, an orally bioavailable, highly specific CDK4/6 inhibitor, causes cell cycle arrest and tumor growth inhibition in multiple preclinical models with intact retinoblastoma protein (pRb+). Methods: Pts withpRb+ advanced solid tumors and lymphomas were treated with escalating doses of LEE011 on a 21-of-28-d or continuous schedule. Dose escalation was guided by a Bayesian Logistic Regression Model with overdose control principle. Primary objective: to establish the MTD and/or RP2D of LEE011. Secondary objectives: safety, efficacy, PK, and PD. Results: As of Jan 17, 2014, 132 pts were treated; 85 during escalation (50–1200 mg/d) and 47 during RP2D expansion. The following results are from dose escalation (data cut-off: July 2, 2013). Ten DLTs were observed in 10 pts: neutropenia (3 pts); asymptomatic thrombocytopenia (2 pts); mucositis, pulmonary embolism, hyponatremia, QTcF prolongation (>500 ms), and increased creatinine (1 pt each). The MTD and RP2D were declared as 900 and 600 mg/d on 21-of-28-d schedules, respectively. The most common study drug-related AEs (all grades) were neutropenia (40%), leukopenia (36%), nausea (35%), and fatigue (27%). G3/4 AEs included neutropenia (19%), lymphopenia (14%), and leukopenia (12%). Asymptomatic QTcF prolongation (>450 ms) was seen at doses ≥600 mg/d: in 10% of pts at 600 mg/d and in 27% of pts at doses >600 mg/d. Plasma exposure increases were slightly higher than dose proportional; mean T1/2 at RP2D was 36.2 h. Paired skin biopsies from 40 pts showed reductions of ≥50% from baseline in Ki67 and phospho-pRb in 55% and 42% of samples, respectively. Among 70 evaluable pts, 2 (2.9%; 600 mg/d) had confirmed PRs: 1 pt with PIK3CA-mut, CCND1-amp, ER+ breast cancer; 1 pt with BRAF/NRAS-WT, CCND1-amp melanoma. SD for ≥4 and ≥6 cycles was seen in 26% and 14% of pts, respectively. Conclusions: LEE011 showed an acceptable safety profile, dose dependent plasma exposure, evidence of target inhibition and preliminary signs of clinical activity. The study expansion is confirming safety and efficacy. Further studies are investigating LEE011 as a single agent (neuroblastoma and malignant rhabdoid tumors) and in combination with other agents (breast cancer and melanoma). Clinical trial information: NCT01237236.