tbuckley/cabot-search huggingface dataset:
EXPECTORANTS AND RESPIRATORY TRACT FLUID
Authors: ELDON M. BOYD
Journal: Pharmacological Reviews (1954)

Expectorants may be defined as drugs which augment the output of respiratory tract fluid and are available for use in the therapy of cough due to irritation from lack of sufficient demulcent respiratory tract fluid below the epiglottis.

Respiratory tract fluid may be collected quantitatively through a cannula ligated into the trachea under certain standardized conditions. Published data upon the method of collection, source, volume, composition, autonomic control, functions, excretion and disposal of, and effect of anaesthetics upon, respiratory tract fluid have been reviewed.

Evidence that the following drugs may affect the output and composition of respiratory tract fluid and the mechanism of their action have been reviewed; ammonium chloride and carbonate, potassium citrate, potassium iodide and certain organic iodides, parasympathomimetic agents, aminophylline, ipecacuanha, various saponins and glycosides, volatile oils, terebene, terpin hydrate, tolu balsam, creosote, certain guaiacols, paregoric, chloroform and certain sulphonamides.

The following drugs have no expectorant effect: syrup, morphine, methadone, codeine, dihydrocodeinone, racemorphan, dextromethorphan, diphenhydramine, chlorprophenpyridamine and bromazine.
Cisplatin-encapsulated nanoparticles inhibit prostate tumor progression via cancer cell-specific targeting
Authors: Rajesh Singh, Shailesh Singh, Udai P. Singh, James W. Lillard
Journal: Cancer Research (2006)

3078   Chemotherapy remains one choice of treatment for prostate cancer, but modest drug responses and significant toxicities by conventional methods of administration limit their efficacy. In our study, we determined the use of cis-Diammineplatinum (II) dichloride loaded (Cisplatin) biodegradable nanoparticles (
Exercise flow-volume loops in children & adolescents with congenital heart disease
Authors: Paolo Pianosi, Mark Wylam
Journal: European Respiratory Journal (2014)

BACKGROUND: Airflow limitation may be an occult cause of exercise intolerance in congenital heart disease (CHD). We examined exercise tidal flow-volume loop analysis to determine the presence or absence of ventilatory limitation to exercise.

METHODS: Subjects performed a maximal cycle ergometer test to voluntary exhaustion. Gas exchange was measured breath-by-breath using a MedGraphics CPX/D (Breeze software, Medical Graphics Corp) which also computed percent flow limitation (%FL, percentage of exercise V t where flow equaled or exceeded the maximum expiratory flow-volume envelope). 4/5 patients had chest CT to examine tracheal calibre. Routine spirometry included MVV by 12-sec sprint method.

RESULTS: Sample exercise tidal flow-volume loops is shown in Figure

View this table:

Patients, diagnoses, and maximal exercise data.





![Figure][1] 



CONCLUSION: Convential mesurement of maximal exercise V e /MVV failed to identify exercise airflow limitation. Flow limitation occurs CHD patients with enlarged/malpositioned great vessels and is best determined by analysis of exercise flow-volume loop.

 [1]: pending:yes
Panorama 1: A randomized, double-blind, phase 3 study of panobinostat or placebo plus bortezomib and dexamethasone in relapsed or relapsed and refractory multiple myeloma.
Authors: Paul G. Richardson, Vania T.M. Hungria, Sung-Soo Yoon, Meral Beksac, Meletios A. Dimopoulos, Ashraf Elghandour, Wieslaw W. Jedrzejczak, Andreas Guenther, Thanyaphong Na Nakorn, Noppadol Siritanaratkul, Robert L. Schlossman, Jian Hou, Philippe Moreau, Sagar Lonial, Jae Hoon Lee, Hermann Einsele, Monika Sopala, Bourras-Rezki Bengoudifa, Claudia Corrado, Jesùs F. San-Miguel
Journal: Journal of Clinical Oncology (2014)

8510^ Background: Panobinostat (PAN) is a potent pan-deacetylase inhibitor that demonstrates synergistic antimyeloma activity when combined with bortezomib (BTZ) + dexamethasone (Dex). Early studies demonstrated durable responses in patients (pts) with relapsed (Rel) and relapsed/refractory (RR) multiple myeloma (MM) treated with PAN + BTZ + Dex. This initiated the PANORAMA 1 study, presented herein. Methods: Eligible pts had Rel or RR (excluding BTZ- and primary-ref MM) following 1-3 prior regimens. Pts received oral PAN (20 mg) or placebo (pbo) 3 ×/wk + IV BTZ (1.3 mg/m2; D 1, 4, 8, 11) during wks 1-2 with oral Dex (20 mg) on the days of and after BTZ in treatment phase (TP) 1, eight 3 wk cycles. Pts demonstrating benefit could proceed to TP2, with PAN dosing maintained and BTZ/Dex less frequent. The primary endpoint was progression free survival (PFS) with response assessed by modified EBMT criteria. Other endpoints included overall survival (OS), overall response rate (ORR), near complete/complete response (nCR/CR) rate, duration of response (DOR), and safety. PFS/ORR was confirmed by an independent review committee. Results: A total of 768 pts (PAN + BTZ + Dex [n = 387]; pbo + BTZ + Dex [n = 381]) were randomized. Median age was 63 y (42% ≥ 65 y) and 48% received ≥ 2 prior regimens. Prior therapies included BTZ (43%), thalidomide (51%), lenalidomide (20%), and 25% received both prior BTZ + IMiDs. The primary endpoint was met with median PFS of 12 mo vs 8.1 mo (P < .0001; HR 0.63, 95% CI [0.52, 0.76]) for pts treated on the PAN vs pbo arm. In the PAN and pbo arms, ORR was 61% vs 55% and nCR/CR rate was 28% vs 16%, with DOR of 13.1 mo vs 10.9 mo, respectively. OS data is not mature. Adverse events (AEs) led to discontinuation in 36% in the PAN arm and 20% in the pbo arm. Common grade 3/4 lab abnormalities and AEs (regardless of study drug relationship) in the PAN vs pbo arms included thrombocytopenia (67% vs 31%), neutropenia (35% vs 11%), and diarrhea (26% vs 8%); these were generally manageable with dose reduction/supportive care. On-treatment deaths occurred in 8% and 5%, respectively. Conclusions: PAN + BTZ/Dex significantly improves PFS in pts with Rel or RR MM, with manageable toxicity. Clinical trial information: NCT01023308.
When theory trumps ideology: Lessons from evolutionary psychology
Authors: Joshua M. Tybur, Carlos David Navarrete
Journal: Behavioral and Brain Sciences (2015)

Abstract Evolutionary psychologists are personally liberal, just as social psychologists are. Yet their research has rarely been perceived as liberally biased – if anything, it has been erroneously perceived as motivated by conservative political agendas. Taking a closer look at evolutionary psychologists might offer the broader social psychology community guidance in neutralizing some of the biases Duarte et al. discuss.
Evaluation of the prevelance of obstructive sleep apnea in children who have narrow maxilla or retrognathic mandibula with habitual snoring
Authors: Eser Capan, Hulya Kilicoglu, Esen Kiyan, Refika Ersu
Journal: European Respiratory Journal (2013)

Bachground:  Obstructive sleep apnea syndrome (OSA) is a disorder of breathing during sleep characterized by prolonged partial upper airway resistance and intermittent partial or complete obstruction that disrupts normal ventilation. OSA in pediatric population is estimated to be 2-3%. Habitual snoring in a prevelance of 6-12 % is the primary symptom in pediatric population however apnea can be determined in only 10-30% of these children. Skeletal problems such as transverse maxillary constriction and mandibular retrognathia increases the risk of OSA. The aim of this study is to evaluate the prevelance of OSA in children who have narrow maxilla or retrognathic mandibula with habitual snoring.  Methods:  Polysomnography was performed in 36 children (15 girl, 21 boy) between the ages of 8-14 who have narrow maxilla or retrognathic mandibula with habitual snoring. The children with retrognathic mandibula had the SNA angle less than 80° and ANB angle greater than 4° and the children with narrow maxilla had bilateral cross bite. Of these 36 children 7 had narrow maxilla and 29 had retrognathic mandibula. Results:  Of the 7 children who had narrow maxilla; severe OSA was present in 2 and mild OSA in 2. Of the 29 children who had retrognathic mandibula; severe OSA was present in 2, moderate OSA in 1 and mild OSA in 4.  Conclusions:  OSA was determined in the 30.5% of the study sample. This finding shows that the children who have narrow maxilla or retrognathic mandibula with habitual snoring are in the high risk group in terms of OSA.
Further Peripheral Vascular Dysfunction in Heart Failure Patients With a Continuous-Flow Left Ventricular Assist Device
Authors: Melissa A.H. Witman, Ryan S. Garten, Jayson R. Gifford, H. Jonathan Groot, Joel D. Trinity, Josef Stehlik, Jose N. Nativi, Craig H. Selzman, Stavros G. Drakos, Russell S. Richardson
Journal: JACC Heart Failure (2015)
Quality of Life in Cystic Fibrosis
Authors: Janice Abbott, Kevin Webb, Mary Dodd
Journal: Journal of the Royal Society of Medicine (1997)

Advances in the management and care of patients with cystic fibrosis (CF) has led to the majority of patients surviving into adulthoodl. Whether this longevity has added 'quality years' to the lives of CF patients is a question which needs to be addressed. The aim of quality of life (QoL) measurement in cystic fibrosis should be to quantify and evaluate the impact of both the disease and its treatments on the wider aspects of the patient's life. Many patients appear to be living normal, independent lives regardless of the demanding treatment regimens and impaired lung function. Additionally, psychosocial functioning in CF patients has been reported to be similar to that of their healthy peers2, which suggests that these aspects of their QoL are good. Only a few studies, however, have directly measured QoL in CF and the interpretation of the data is largely problematic.
The association among balance, activity limitation, dyspnea and vulnerability in chronic obstructive pulmonary diseases
Authors: Neslihan Durutürk, Eda Tonga
Journal: European Respiratory Journal (2013)

Evidence suggests that individuals with COPD have important deficits in balance control. The objective of this study was to investigate the relationship between balance, activity limitation, dyspnea and vulnerability in COPD. 59 clinically stable patients (mean age:65,19±10,62, FEV1: 44.8±10.2 %pred) participated in our study. Balance were determined using Timed Up and Go Test (TUG) and balance confidence using the Activity-Specific Balance Confidence (ABC) Scale. Activity performance was evaluated with Canadian Occupational Performance Mesure (COPM). Daily living activities was assesed by London Chest Activities of Daily Living (LCADL) scale. Medical Research Council Dyspnea (MRCD) scale was used to determine dyspnea. Vulnerability were determined using Vulnerable Elders Survey (VES-13). There were significantly negative correlation between ABC scores and LCADL leisure time activities subgroup (p:0,029, r:-0,284) and between ABC with VES-13 self related health subgroup (p:0,004, r:-0,366). There were positive correlation between TUG and LCADL household activities (p:0,012, r:0,326), and between TUG and LCADL leisure time activities (p:0,034, r:0,277). There was no correlation between balance and dyspnea symptoms of the subjects. The correlation between COPM performance and VES-13 self related health subgroup (p:0,011, r:-0,330) were significant. Consequently the study showed that balance deficits effects activities of daily living and vulnerability significantly. Activity performance negatively influence health deteriotion in patients with COPD. This study also indicated that balance assesment and training should be added to the COPD rehabilitation programmes.
Continuing medical education: A contribute of the pneumologists in the pre-hospital medicine
Authors: Paolo Michele Olia, Alessandro Querci
Journal: European Respiratory Journal (2011)

Untill now in Tuscany, the doctors of the Ambulance Service 118 originate from general practitioners after specific qualifying courses, usually directed by resuscitators. In 1999, in Italy, was activated the Continuing Medical Education (CME) and in 2002 the Tuscan Region acknowledged the provisions in the matter. As our ambulance patients present a considerable number of low oxyhemoglobin saturations (Olia et al., ERJ 2003: 44s, 381s), formative events in respiratory diseases were carried out, involving specialists in respiratory medicine as teachers. The events were: emergency management of airways, acute respiratory failure, use of mechanical ventilators during ambulance transfers, alternative devices to intubation, CPAP and non invasive ventilation, oxygen therapy.  Formative events were unrolled in 4 hours meetings. At the end of meetings, learning and approval tests were carried out, for acquire the CME credits. Participants had to replay correctly at last the 80% of the questions and to attend the lesson9s time. Moreover 2 short meetings of 2 hours each, were carried out and related to some aspects of respiratory fatigue and spontaneous pneumothorax. 382 hours of specialized formation, the 9% of all the formative hours dispensed from 2003 to 2010 by our Service, were delivered. 100% of the participants found interesting the treated topics; 98.9±1.8% found them useful in theory and the 98.3±2.9% in practice.  Besides the good results in CME credits, 1 point each hour, important concepts and techniques, from the point of view of the pneumologists were explained, showing a further vision of the respiratory emergencies and their management in the pre-hospital medicine.
Impact of speed and age on an office based advanced driving simulator (MinUoLDS) between obstructive sleep apnoea syndrome (OSAS) patients and controls
Authors: Akshay Dwarakanath, Dipansu Ghosh, Samantha Jamson, Mark Elliott
Journal: European Respiratory Journal (2014)

Introduction   Untreated OSAS is associated with increased likelihood of being involved in road traffic accidents. We have previously shown that controls perform better on the MiniUoLDS than OSAS patients. Evaluating the fail category, we hypothesised that higher speed and age may be contributing factors both in controls and OSAS patients.   Methods   154 (Age 53 +/- 12, ESS 14+/-7, ODI 40+/- 26) untreated OSAS patients and 110 controls (Age 55+/-15, ESS 4+/- 3) were included. All performed a 90km motorway driving simulation, which included 8 epochs. The mean speed during the simulation and the age of the subjects were compared between the two groups. The MiniUoLDS outcomes fail or no fail was based on preset criteria.   Results   Controls who failed the MiniUoLDS had a significantly higher mean speed as compared to other groups. A hierarchical pattern in the mean speed was noted between controls and patients.  Despite driving at a slower speed, some OSAS patients failed the MiniUoLDS. The outcome on the MiniUoLDS was not age dependent between OSAS patients and controls.   Conclusion   Higher speed may be a possible contributing factor in controls but not in OSAS patients who failed the MiniUoLDS. The outcome on the MiniUoLDS is not age dependent both in OSAS patients and controls. These factors should be considered when developing a driving simulator in the future.
New Insulin Glargine 300 Units·mL−1 Provides a More Even Activity Profile and Prolonged Glycemic Control at Steady State Compared With Insulin Glargine 100 Units·mL−1
Authors: Reinhard H.A. Becker, Raphael Dahmen, Karin Bergmann, Anne Lehmann, Thomas Jax, Tim Heise
Journal: Diabetes Care (2014)

OBJECTIVE To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of a new insulin glargine comprising 300 units·mL−1 (Gla-300), compared with insulin glargine 100 units·mL−1 (Gla-100) at steady state in people with type 1 diabetes. RESEARCH DESIGN AND METHODS A randomized, double-blind, crossover study (N = 30) was conducted, applying the euglycemic clamp technique over a period of 36 h. In this multiple-dose to steady-state study, participants received once-daily subcutaneous administrations of either 0.4 (cohort 1) or 0.6 units·kg−1 (cohort 2) Gla-300 for 8 days in one treatment period and 0.4 units·kg−1 Gla-100 for 8 days in the other. Here we focus on the results of a direct comparison between 0.4 units·kg−1 of each treatment. PK and PD assessments performed on the last treatment day included serum insulin measurements using a radioimmunoassay and the automated euglycemic glucose clamp technique over 36 h. RESULTS At steady state, insulin concentration (INS) and glucose infusion rate (GIR) profiles of Gla-300 were more constant and more evenly distributed over 24 h compared with those of Gla-100 and lasted longer, as supported by the later time (∼3 h) to 50% of the area under the serum INS and GIR time curves from time zero to 36 h post dosing. Tight blood glucose control (≤105 mg·dL−1) was maintained for approximately 5 h longer (median of 30 h) with Gla-300 compared with Gla-100. CONCLUSIONS Gla-300 provides more even steady-state PK and PD profiles and a longer duration of action than Gla-100, extending blood glucose control well beyond 24 h.
Gleevec-mediated inactivation of Akt regulates ABCG2 function in head and neck squamous cell carcinoma
Authors: Theresa S. Chu, Jocelyn S. Chen, Jay P. Lopez, Yi An, Francisco S. Pardo, Joseph Aguilera, Weg M. Ongkeko
Journal: Cancer Research (2006)

1268   The ATP binding cassette protein ABCG2 (ABCP/MXR/BCRP) has been suggested to be involved in the resistance against various anticancer drugs. Many cell lines selected for resistance to numerous chemotheurapeutic drugs have been shown to overexpress ABCG2. Recent studies show that Imatinib mesylate (Gleevec, STI571) reverses ABCG2-mediated drug resistance to topotecan and SN-38. In addition, we have previously reported that Gleeve down-regulates Akt (PKB) kinase activity, which is elevated in head and neck squamous cell carcinoma (HNSCC). Akt is a downstream target in the phosphatidylinositol 3-kinase (PI3K) pathway and has been shown to regulate cellular growth and survival, tumorigenesis and drug resistance. Akt recently has also been implicated in the translocation of ABCG2 from the cell surface in LLC-PK1 cells. Therefore, we investigated whether the reversal of ABCG2 mediated drug resistance by Gleevec is caused by the down-regulation of the Akt kinase. Hoechst 33342 dye or doxorubicin was incubated with the HNSCC cells, and flow cytometry was used to determine the levels of extrusion from the cells. Cells with high Hoechst extrusion are termed side population (SP) cells. Our results suggest that Gleevec may be regulating doxorubicin drug resistance through Akt. To investigate this, Akt kinase inhibitors LY294002 and 1L-6-Hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (1L-6), transfection with siRNA Akt or a dominant negative Akt plasmid, and the tyrosine kinase inhibitor Gleevec were used to show that these treatments resulted is at least a 50% decrease in SP for each treatment. Doxorubicin extrusion flow cytometry studies also demonstrate a significant decrease in doxorubicin efflux of HNSCC cells treated with Gleevec, 1L6, and transfection with si-RNA Akt. To examine a possible mechanism for this drug resistance, Western blot and immunofluorescence were performed to study ABCG2. Similar to previous reports, our data suggests ABCG2 translocation as the mechanism to which Gleevec and Akt regulate drug resistance. In order to demonstrate the cellular effects of the proposed regulation of drug resistance, a clonogenic survival assay was performed with incubation of Gleevec and doxorubicin. This resulted in a dose-dependent decrease in cell survival compared to cells in the control population, further confirming the reversal of drug resistance via the regulation of ABCG2. Taken together, our findings demonstrate that Gleevec confers greater doxorubicin retention presumably via inhibition of Akt which regulates ABCG2 function. Ultimately, elucidating the role of Akt in the regulation of ABCG2-mediated drug resistance may support future studies of Akt as regulator in other chemotherapeutic drug resistance.
Activation (Tyrosine Phosphorylation) of ErbB-2 (HER-2/neu): A Study of Incidence and Correlation With Outcome in Breast Cancer
Authors: A.D. Thor, S. Liu, S. Edgerton, D. Moore, K.M. Kasowitz, C.C. Benz, D.F. Stern, M.P. DiGiovanna
Journal: Journal of Clinical Oncology (2000)

PURPOSE: We hypothesize that phosphorylated ErbB-2 (P-ErbB-2, identified by a novel antibody PN2A) may provide either more significant or additional prognostic marker data for breast cancer patients. This study was designed to compare the incidence and prognostic value of ErbB-2 (HER-2/neu) and P-ErbB-2 immunoexpression in archival breast cancer samples. MATERIALS AND METHODS: Eight hundred sixteen invasive breast cancers with a median of 16.3 years of follow-up were immunostained for ErbB-2 (using antibody CB11) and P-ErbB-2 (using antibody PN2A). ErbB-2 and P-ErbB-2 data were compared with clinical, histologic, immunohistochemical, and outcome variables. RESULTS: Of 816 primary breast cancers, 307 (38%) were positive for ErbB-2 and 37 (12% of ErbB-2 positive and 5% of the study population) expressed P-ErbB-2. P-ErbB-2 was not detected in ErbB-2–negative cases (n = 509). ErbB-2 immunohistochemical data were bimodal; patients with ≥ 80% cellular expression had the shortest disease-free and disease-specific survival. P-ErbB-2 was associated with a higher percentage of ErbB-2–positive cells, a higher number of positive lymph nodes, and cellular proliferation. ErbB-2 and P-ErbB-2 were indicators of poor prognosis in node-positive patients in both univariate and multivariate analyses. We found that either P-ErbB-2 expression or high (≥ 80%) ErbB-2 expression provided the most significant prognostic value in node-positive cases by multivariate analyses. There were too few P-ErbB-2–positive cases and events in the node-negative patient group to allow statistical analysis of P-ErbB-2 in that subgroup. CONCLUSION: PN2A immunostaining identified a subset (approximately 12% of ErbB-2–positive breast cancers) with activation (phosphorylation) of the receptor ErbB-2. P-ErbB-2 expression was strongly associated with higher levels of ErbB-2 expression (≥ 80%), although it was not a surrogate. Identification of cases with a high percentage of invasive breast cancer cells expressing ErbB-2 or determination of receptor activation via P-ErbB-2 may provide additional prognostic value in node-positive breast cancers.