tbuckley/cabot-search huggingface dataset:
Enzalutamide in men with chemotherapy-naive metastatic prostate cancer (mCRPC): Results of phase III PREVAIL study.
Authors: Tomasz M. Beer, Andrew J. Armstrong, Cora N. Sternberg, Celestia S. Higano, Peter Iversen, Yohann Loriot, Dana E. Rathkopf, Suman Bhattacharya, Joan Carles, Johann S. De Bono, Christopher P. Evans, Anthony M. Joshua, Choung-Soo Kim, Go Kimura, Paul N. Mainwaring, Harry H. Mansbach, Kurt Miller, Sarah B. Noonberg, Peter M. Venner, Bertrand Tombal
Journal: Journal of Clinical Oncology (2014)

LBA1^ Background: Enzalutamide, an orally administered androgen receptor inhibitor, improved overall survival (OS) in men with mCRPC who had received prior docetaxel therapy (Scher et al, NEJM 367:13, 2012). This study examined whether enzalutamide could prolong OS and radiographic progression-free survival (rPFS) in asymptomatic or mildly symptomatic chemotherapy-naive men with mCRPC. Methods: In this randomized, double-blind, placebo-controlled, multinational phase 3 study (NCT01212991), chemotherapy-naive patients with mCRPC were stratified by site and randomized 1:1 to enzalutamide 160 mg/day or placebo. OS and rPFS were co-primary endpoints and analyzed for the intent-to-treat population. Planned sample size was 1,680 with 765 deaths to achieve 80% power to detect a target OS hazard ratio (HR) of 0.815 with a type I error rate of 0.049 and a single interim analysis at 516 (67%) deaths. The co-primary endpoint of rPFS had sufficient power to detect a target HR of 0.57 and a type I error rate of 0.001 with a minimum of 410 events. Results: A total of 1,717 men were randomized (1,715 treated) between September 2010 and September 2012. The interim analysis at 539 deaths showed a statistically significant benefit of enzalutamide over placebo with a 30% reduction in risk of death (OS: HR 0.70; 95% CI: 0.59-0.83; P&lt; 0.0001) and an 81% reduction in risk of radiographic progression or death (rPFS: HR 0.19; 95% CI: 0.15-0.23; P&lt; 0.0001). At the time of the analysis, 28% of enzalutamide patients and 35% of placebo patients had died. Estimated median OS was 32.4 months (mo) (95% CI, 31.5–upper limit not yet reached [NYR]) in the enzalutamide arm vs 30.2 mo (95% CI, 28–upper limit NYR) in the placebo arm. Median rPFS was NYR (95% CI: 13.8–upper limit NYR) in the enzalutamide arm vs 3.9 mo (95% CI: 3.7-5.4) in the placebo arm. Seizure events were reported in two patients. The Independent Data Monitoring Committee considered the benefit-risk ratio to favor enzalutamide and recommended stopping the study and crossing placebo patients to enzalutamide. Secondary endpoints and safety analysis will be presented. Conclusions: Treatment with enzalutamide significantly improves OS and rPFS in men with chemotherapy-naive mCRPC. Clinical trial information: NCT01212991.
Halve added sugar in diet to 5%, say nutritionists
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

GM-CSF is an essential cytokine for normal lung immune homeostasis. In the current studies we examined the role of GM-CSF and its lung-specific conditional overexpression on the host immune response to influenza. Transgenic <i>tet-GM<sup>+/+</sup></i> mice were intranasally infected with A/PR8/34 H1N1 IAV, BALF was collected and single cell lung suspensions were generated using collagenase/DNase digestion. IAV infection induced a prolonged period of GM-CSF deficiency in the lung environment. "Early" (3 days prior to infection) induction of GM-CSF led to protection characterized by significantly enhanced weight recovery as compared to non-induced mice, as well as increased numbers of CD11c<sup>+</sup> cells, including CD11b<sup>+</sup> and CD11b<sup>-</sup> dendritic cells as well as enhanced recovery of CD11c<sup>+</sup> Siglec-F<sup>+</sup> AMs. Interestingly, the weight recovery curves for "late" (3 days post-infection) as compared to "early" GM-CSF overexpression were similar suggesting that GM-CSF may have a role in the resolution of inflammation. Indeed, local GM-CSF restoration caused decreased the frequencies of inflammatory Ly-6C+ monocytes/macrophages and Ly-6G+ neutrophils. Lastly, "late" GM-CSF overexpression accelerated secretion of anti-IAV IgA antibody in BALF. These results indicate viral-induced GM-CSF deficiency impairs recovery from influenza infection, yet can be corrected with exogenous administration of GM-CSF.
Soluble CD23 reliably reflects disease activity in B-cell chronic lymphocytic leukemia.
Authors: W Reinisch, M Willheim, M Hilgarth, C Gasché, R Mader, S Szepfalusi, G Steger, R Berger, K Lechner, G Boltz-Nitulescu
Journal: Journal of Clinical Oncology (1994)

PURPOSE This study was initiated to evaluate whether soluble CD23 (sCD23) reflects disease activity and tumor load in B-cell chronic lymphocytic leukemia (B-CLL) and to determine its prognostic potential for this disease. PATIENTS AND METHODS The concentration of sCD23 was measured in the serum of 45 B-CLL patients, 50 patients with other lymphoproliferative disorders, and 41 healthy donors (HD). sCD23 serum levels from B-CLL patients were correlated with parameters of disease activity and total tumor mass (TTM) score. In selected cases, sCD23 was measured repeatedly over a 24-month period. Expression, density, and calculated total amount of membrane CD23 on peripheral-blood B-CLL cells, as well as its correlation to sCD23 levels in serum and supernatants, were determined. RESULTS sCD23 in B-CLL patients serum was highly elevated as compared with other lymphoproliferative disorders, with the exception of immunocytoma (IC). Both advanced Rai stages and active forms of B-CLL were associated with higher levels of sCD23. There was a highly significant reciprocal relationship between sCD23 and lymphocyte count doubling time (LCDT). Serum sCD23 correlated positively with serum deoxythymidine kinase activity and TTM score, but not with absolute lymphocyte counts. The repetitive measurement of serum sCD23 showed the usefulness of this marker in monitoring disease progression in B-CLL. The total amount of membrane CD23 on in vitro-cultured B-CLL cells correlated significantly with sCD23 levels in the supernatant, whereas correlation between serum sCD23 and membrane CD23 on freshly isolated B-CLL cells was absent. CONCLUSION Our results indicate that sCD23 is a highly sensitive and specific parameter with prognostic potential for B-CLL, which may be used as a tumor marker and may help to assess disease activity.
Inhibition of human cationic glutathione S -transferase by nonsubstrate ligands
Authors: Thomas D. Boyer, Donald A. Vessey
Journal: Hepatology (1987)

Inhibition of a major hepatic form of human cationic glutathione S-transferase by bilirubin, biliverdin, indocyanine green and chenodeoxycholic acid was investigated as a function of pH (range = 6.5 to 9.1). Changes in pH had little effect on the extent of inhibition by indocyanine green. However, inhibition by bilirubin, biliverdin and chenodeoxycholic acid was found to be pH-dependent, with markedly less inhibition at the high values of pH. The reduced inhibition at the high values of pH could not be ascribed to a failure of the enzyme to bind the nonsubstrate ligand. Instead, the complete inhibition observed at pH 6.5 became partial (hyperbolic) inhibition at pH 9.1. This behavior can be ascribed to the binding of the nonsubstrate ligands at a site other than the active site, i.e., at high values of pH there is formation of an enzyme-substrate-inhibitor complex which still retains considerable catalytic activity. At physiologic values of pH (7.0), the human transferase was completely inhibited by saturating concentrations of the tested nonsubstrate ligands. This is in contrast to our previous studies performed with the rat transferases where, although inhibition also was affected by buffer pH, some forms of the enzyme retained significant catalytic activity at pH 7.0 despite high concentrations of nonsubstrate ligands. We conclude that the ability of the human cationic glutathione S-transferases to serve as enzymes of detoxification in the presence of high intracellular concentrations of nonsubstrate ligands may be significantly reduced, and this may render the cholestatic liver unusually susceptible to injury by toxic electrophiles.
Emergence of VIM-4 metallo-β-lactamase-producing Klebsiella pneumoniae ST15 clone in the Clinical Centre University of Pécs, Hungary
Authors: S. Melegh, K. Kovács, T. Gám, A. Nyul, B. Patkó, A. Tóth, I. Damjanova, G. Mestyán
Journal: Clinical Microbiology and Infection (2013)
Performances of real time PCR for diagnosis of respiratory tuberculosis. Does it replace 3 day micorscopic sputum examination
Authors: Miok Kim, So Yeon Yoo, Jong Hoo Lee, Jaechun Lee, Young Ree Kim
Journal: European Respiratory Journal (2013)

Background: PCR is a widely used method for rapid and accurate clinical diagnosis of mycobacteriosis. Initially respiratory tuberculosis is diagnosed by chest x-ray and direct microscopy of three sputum samples following result of Tb culture.Three day sputum sampling is inconvenient for patient.We find out whether one day PCR plus same day one acid-fast bacilli(AFB) smear of expectorated sputum is more helpful than three day micorscopy test for initial diagnosis in outpatient clinic.  Method:We conducted a prospective observational study of patients with respiratory tuberculosis who visited outpatient clinic between March 2009 and March 2011 in Jeju National University Hospital, Jeju,Korea.We compare baseline characterics, chest x-ray, Tb culture and one day PCR plus same day one AFB smear of expectorated sputum sample with AFB smear of three day sputum samples.  Rusults: A total 224 patients(112 PCR group,112 microscopy only group) were evaluated. PCR group is older than microscopic group. Overall Tb culture positive rate is 32.1%(37 PCR group,35 microscopy only group). Among 37 Tb culture postive cases PCR positive for Tb is 35 cases (94.6%). Initial diagnostic rate is higher of PCR plus micorscopy group (37.5% vs. 17.9%; p   Concusion: One day PCR plus same day one AFB smear of expectorated sputum has the potiental to be a effective and convenient tool.
Abstract 21424: Inflammatory Imbalance Assessed by Fetuin-A and CRP Level is a Srong Predictor of Outcome in Acute Coronary Syndromes (From Fast-mi Registry)
Authors: Pascal Lim, Nicolas Danchin, Tabassome Simon, Stephane Moutereau, Romain Cador, Olivier Claudon, Frederic Marco, Pierre Fournier, Pascal Gueret
Journal: Circulation (2010)
Non-Attendance at Ophthalmology Outpatient Clinics
Authors: T Potamitis, P B Chell, H S Jones, P I Murray
Journal: Journal of the Royal Society of Medicine (1994)

Non-attendance at outpatient clinics is a common problem, resulting in inefficiency and wasted resources. To establish the reasons why patients failed to attend their outpatient clinic appointment and to assess what proportion of these failed attendances were potentially preventable, we conducted a 13-month prospective postal survey of clinic non-attenders to our hospital. Of 5248 appointments made during the study, 521 were not kept (9.9%). Of these, 224 patients replied to the questionnaire, a response rate of 43%, with new patients more likely to not attend than old patients (odds ratio 2.7, P < 0.001). From the replies, 27.3% of non-attendances could be described as 'clerical error' with a further 17.9% due to patients failing to remember their appointment. Based on the replies received, a better organized outpatient booking system and a simple postal reminder could potentially prevent at least 40% of non-attendances.
Different effects of adaptive servoventilation therapy in awake and asleep heart failure patients with Cheyne-Stokes respiration and healthy volunteers
Authors: Jens Spießhöfer, Jessica Heinrich, Christina Efken, Roman Lehmann, Thomas Bitter, Dieter Horstkotte, Olaf Oldenburg
Journal: European Respiratory Journal (2013)

Cheyne-Stokes respiration (CSR) in heart failure (HF) is characterized by chronic hyperventilation with low-normal to depressed pCO 2 . Adaptive servoventilation therapy (ASV) was introduced to stabilize respiration in these patients. This study investigates acute effects of ASV on pCO 2  and oxygen saturation (SaO 2 ) in HF patients with CSR and healthy volunteers (HV), respectively.  HF patients (EF ≤ 50%, NYHA ≥ II) with CSR (AHI ≥ 15/h) and HV were ventilated using a new ASV device (PaceWace™, ResMed) for 1h. PCO 2  and SaO 2  were assessed transcutaneously, while vigilance was analyzed using EEG recordings. Results were obtained during ASV ventilation while awake and asleep and compared to those being obtained 30 minutes before and after ventilation.  A total of 20 HF patients (19 male; 79±12 years; LV-EF 36±8%; AHI 36±14/h; EPAP 8.9±0.5 cmH 2 O; IPAP 17.1±0.5 cmH 2 O) and 15 HV (13 male, 25±4 years, EPAP 8.4±1.8 cmH 2 O, IPAP 14.5±2.4 cmH 2 O) were included. As compared to baseline values, ASV was accompanied with a decrease in pCO 2  (34.4±3.2 vs. 33.7±3.8mmHg) and an increase in SaO 2  (93.8±2.6 vs. 94.9±2.6%) in HF patients as well as in HV (pCO 2 : 39.5±3.0 vs. 38.2±3.8mmHg, SaO 2 : 96.9±1.3 vs. 97.8±0.9%), as long as they were awake. While asleep, pCO 2  raised and SaO 2  fell in HF patients (pCO 2  36.3±3.8mmHg, SaO 2  93.8±2.6%) as well as in HV (pCO 2  41.7±3.0mmHg, SaO 2  97.1±1.2; p  While CSR in HF patients is characterized by hyperventilation with low pCO2, ASV therapy might lead to further hyperventilation as long as patients are awake. While asleep, pCO 2  increase to mid-normal values while SaO2 stay within normal range.
Leukemias and Vaginal Tumors Induced in Female Donryu Rats by Continuous Administration of l-Butyl-3,3-dimethyl-l-nitrosourea in the Drinking Water2
Authors: Masaya Takeuchi, Akihiko Maekawa, Keizo Tada, Shigeyoshi Odashima
Journal: JNCI Journal of the National Cancer Institute (1976)

Three groups of Donryu rats, each consisting of 36 females, were continuously given solutions of 1-butyl-3,3-dimethyl-1-nitrosourea as drinking water (400 ppm for group A, 200 ppm for group B 100 ppm for group C). Of the 100 rats that survived at least 122 experimental days, 64 developed leukemia and 38 had vaginal tumors. Leukemias were preponderant in animals of groups A and B; vaginal tumors appeared in group C.
Estimates of Composite Risk Factors for Death From Breast Cancer2
Authors: Dean F. Davies, Andre Torng, Elizabeth B. Morris, Jeno Sebes
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Estimates of Composite Risk Factors for Death From Breast Cancer Get access Dean F. Davies, Ph.D., M.D., Dean F. Davies, Ph.D., M.D. 3Department of Community Medicine, College of Medicine, University of Tennessee Center for the Health Sciences, 800 Madison Ave., Memphis, Tenn. 38163. Search for other works by this author on: Oxford Academic PubMed Google Scholar Andre Torng, M.S., Andre Torng, M.S. 3Department of Community Medicine, College of Medicine, University of Tennessee Center for the Health Sciences, 800 Madison Ave., Memphis, Tenn. 38163. Search for other works by this author on: Oxford Academic PubMed Google Scholar Elizabeth B. Morris, R.N., M.S., Elizabeth B. Morris, R.N., M.S. 3Department of Community Medicine, College of Medicine, University of Tennessee Center for the Health Sciences, 800 Madison Ave., Memphis, Tenn. 38163. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jeno Sebes, M.D. Jeno Sebes, M.D. 4Department of Radiology, College of Medicine, University of Tennessee Center for the Health Sciences, 800 Madison Ave., Memphis, Tenn. 38163. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 61, Issue 1, July 1978, Pages 41–48, https://doi.org/10.1093/jnci/61.1.41 Published: 01 July 1978 Article history Received: 27 June 1977 Revision received: 23 January 1978 Accepted: 01 February 1978 Published: 01 July 1978
Assessment of SHOX2 methylation in EBUS-TBNA specimen improves accuracy in lung cancer staging
Authors: Kaid Darwiche, Ruediger Karpf-Wissel, Stefan Welter, Reimo Tetzner, Dirk Theegarten, Lutz Freitag
Journal: European Respiratory Journal (2013)

Introduction:EBUS-TBNA is a well established method to assess mediastinal lymph nodes for lung cancer staging. However, due to the low negative predictive value a high proportion of patients with negative results require further investigations or invasive procedures. The level of SHOX2 gene methylation is a known diagnostic biomarker but its usefulness for lung cancer staging in EBUS-TBNA specimen is unknown.  Methods:EBUS-TBNA was performed from 264 suspicious lymph nodes of 161 patients. Histologic evaluation and SHOX2 DNA methylation real time PCR analysis was performed on EBUS-TBNA specimen. Relative methylation in form of ΔΔCt was used to classify the samples. Negative or ambiguous histologic results were confirmed by surgical means and clinical follow up over 6 months.  Results:In average a 70 fold higher SHOX2 methylation level was measured for positive compared to negative lymph nodes. Using a cutoff from 6.5 ΔΔCt, the SHOX2 assay in combination with EBUS-TBNA histopathological evaluation correctly identified 96% of the lymph nodes with a sensitivity of 94% and a specificity of 100%. Negative predictive value could be improved from 80% to 92% when assessing SHOX2 methylation level to histopathological evaluation of EBUS-TBNA specimen alone.  Conclusion:The combination of histological evaluation and the assessment of SHOX2 methylation level in EBUS-TBNA specimen strongly improves mediastinal lung cancer staging and such avoiding unnecessary surgical exploration.
Risk factors associated with persistent airflow limitation in difficult asthma
Authors: Samira Aouadi, Ghada Ben Ali, Sonia Maalej, Ines Zayani, Bechir Zouari, Ali Ben Kheder, Ikram Drira
Journal: European Respiratory Journal (2012)

Introduction: The clinical manifestations of difficult asthma are heterogeneous. Some patients with difficult asthma develop irreversible airway obstruction, which is associated with poor outcomes.

Objective: the aim of the study is to determine clinical characteristics associated with persistent airflow limitation in difficult asthma.

Methods : we retrospectively analyzed 48 patients with difficult asthma between 2005 and 2010. Twenty patients (8 female, 12 male) with persistent airflow limitation (post bronchodilator FEV1/FVC ratio < 70%) were compared to 28 patients (13 female, 15 male) with normal post bronchodilator FEV1/FVC ratio. Patients with chronic obstructive pulmonary disease and bronchiectasis were excluded.

Results: there was no significant difference between the two groups in age (51 vs 45 years, p=0,17), sex (p=0,66), age of asthma onset (35 vs 32 years, p=0,07), number of hospitalizations (p=0,39) and frequency of exacerbations (p=0,74). Rhinitis was more frequent in patients with normal FEV1/FVC ratio (15% vs 35%). But, the difference was not significant (p=0,11). Gatroesophageal reflux was found in 25% of patients in both groups.

Risk factors associated with persistent airflow limitation were as follows: longer duration of asthma (22 vs 9.5 years, p <0.001), current or past smoking (50% vs 21%, p=0.038) and absence of allergy (69% vs 33%, p=0.026). Dust mite sensitization was significantly more frequent in patients with normal FEV1/FVC ratio (26% vs 61%, p=0,33).

Conclusion: 

Smoking, longer disease duration and absence of sensitization seem to be related to persistent airflow limitation in Tunisian patients with difficult asthma.
Volatile organic compounds (VOC) in exhaled breath in patients with lung cancer, using the analytical technique thermal desorber- gase chromatography-spectrometer mases
Authors: Javier Jareno Esteban, Maria Angeles Munoz Lucas, Belen Carrillo Aranda, Jose Angel Maldonado Sanz, Concepcion Civera Tejuca, Antonio Aguilar Ros, Gema Rodriguez Trigo, Carlos Gutierrez Ortega, Jose Luis Alvarez Sala, Luis Callol Sanchez
Journal: European Respiratory Journal (2012)

AIM : Oxidative stress is increased in lung cancer (LC) and generated volatile organic compounds (VOC). We can detect VOC in exhaled breath using the analytical technique TD / GC / MS. The determination of VOC, may be useful as a noninvasive screening in LC.   OBJETIVE : To determine differences in VOC present in the exhaled breath in 3 groups: LC group, COPD group and clinically healthy volunteers.   METHODS: Case-control study with 81 patients with LC, 40 patients with COPD and 89 healthy volunteers (without respiratory disease). Informed consent accepted. Collection of exhaled breath by means BioVOC™ to functional residual capacity  Analytical technique: TD/GC/MS (Markes-Agilent Tech.)  Statistical analysis: SPSS® v-15 for Windows.   RESULTS: Description of the sample. Quantitative study and qualitative study of VOC.   CONCLUSSIONS :  1-Nonanoic acid is the only VOC with statistical significance between study groups: and it is independent of age and smoke custom.  2. – The probability to find nonanoic acid in LC group is higher than control and COPD groups  3. - Nonanoic acid and heptanal could be useful to discriminate between LC + COPD patients versus LC without COPD patients.  4. - In our sample, nonanoic acid could be useful like a LC tumorlike marker.  Supported by FIS: PI07/1116; Neumomadrid 2008 and SEPAR 2010: PI-881.
Recovery rate of nontuberculous mycobacteria over a 10-year period at a tertiary referral hospital in Korea
Authors: Boksoon Chang, Kyeongman Jeon, O. Jung Kwon, Nam Young Lee, Chang-Seok Ki, Won-Jung Koh
Journal: European Respiratory Journal (2012)

The incidence of nontuberculous mycobacteria (NTM) infection is increasing in Korea. The aim of this study was to evaluate the recovery rate of NTM from respiratory specimens over a 10-year period in a tertiary referral hospital in Korea with a intermediate tuberculosis burden.  We identified all mycobacterial isolates from respiratory specimens at the Samsung Medical Center (Seoul, Korea) obtained from January 2000 to December 2009.  During the study period, 25,374 mycobacterial isolates were recovered from 8,115 patients. The proportion of NTM isolates was continuously increasing from 31.8% (167/525) in 2000 to 68.2% (3,514/5,152) in 2009 ( p  p  Mycobacterium avium  complex (n= 4,734, 52%) and  Mycobacterium abscessus  complex (n=2,660, 29%).  This study found a rapidly increasing trend in the isolation of NTM from respiratory specimens at a referral hospital in Korea. The high proportion of NTM even among AFB-positive respiratory specimens would represent serious challenge for the diagnosis of pulmonary tuberculosis.
Smoking habits and smoking behaviour of staff in Institutions for lung diseases and tuberculosis
Authors: Anita Popovska, Maja Zakoska
Journal: European Respiratory Journal (2014)

The advice and encouragement of health staff can be a powerful force in smoking cessation. Smoking habits of health staff in Institutions for lung disease and tuberculosis in Republic of Macedonia were aim of our investigation. We made a survey with an anonymous questionnaire among 442 occupied in these Institutions. 192 (43,44 %) of them were smokers and 250 (56,56%) non smokers. Between smokers 160 (44,82 %) were female and 32 (37,65%) males. Regarding the Fagenstrom questionnaire percentage of nicotine addiction is low at 58 (30,21 %), middle at 91 (47,40%) and high at 43 (22,39%). Pack years was to 10 at 40 (20,83 %), from 10-20 at 110 (57,29%) and higher of 20 at 42 (21,88%). Attempt to stop smoking was never made by 100 (52,08 %), only one or two times 53 (27,60%) and higher of three times 39 (20,32%).From 192 smokers, 58(30,2%) are not interested about smoking habits of their patients and 36(18,7%) are not counselling them to stop smoking. Results of all questionnaire show that smoking is mass phenomenon between health staff. Disrespect of Low for prohibition of smoking as a non professional relation at work means that they are not capable of taking appropriate care for their patients, and in addition that they are in a need of treat to stop smoking. Also they are persons with high percentage of nicotine addiction and encounter big risk for chronic obstructive pulmonary disease and lung carcinoma.

Key words: smoking habits, smoking behaviour, health staff.