tbuckley/cabot-search huggingface dataset:
Initial treatment with CsA-AZA versus FK506-MPA: Comparison of early outcomes after lung transplantation
Authors: Heloïse Masquillier, Robin Vos, David Ruttens, Stijn Verleden, Elly Vandermeulen, Bart Vanaudenaerde, Jonas Yserbyt, Lieven Dupont, Dirk Van Raemdonck, Geert Verleden
Journal: European Respiratory Journal (2013)

Introduction 

Baseline immunosuppression at Leuven University Hospital changed from CsA-AZA to FK506-MPA in March 2011. This study investigates early post-operative outcomes in a cohort 1 year before and 1 year after the conversion of immunosuppression.

Methods 

Cohort 1 (LTx between 03/2010 - 03/2011, n= 58) was initially treated with CsA-AZA and cohort 2 (LTx between 03/2011 - 03/2012, n=65) with FK506-MPA, together with steroids and rATG for 3 days. Exclusion criteria were retransplantation (CsA-AZA n=3, FK506-MPA n=7) and death <6 months post-LTx(CsA-AZA n=3, FK506-MPA n=3). Outcome parameters included acute rejection (AR), lymphocytic bronchiolitis (LB), respiratory infection, need for antirejection therapy, BAL cell profile and FEV1.

Results 

The FK506-MPA cohort demonstrated significantly more LB at 1 month (p=0.029) and 6 months (p=0.031), whereas CsA-AZA patients experienced more AR at 3 months (p=0.048) and needed more episodes of antirejection therapy (steroids) within the first 3 months (p=0.0002) following LTx. BAL neutrophilia was persistently, although not significantly, higher in FK506-MPA. Infection rates and FEV1%pred were comparable between both cohorts.

Discussion 

FK506-MPA as initial immunosuppressive treatment results in less early AR and early anti-rejection therapy, but more early LB and BAL neutrophilia. The possible effect on development of CLAD and survival remains to be awaited.

![Figure][1]  [1]: pending:yes
Has growth in electronic cigarette use by smokers been responsible for the decline in use of licensed nicotine products? Findings from repeated cross-sectional surveys
Authors: Emma Beard, Jamie Brown, Ann McNeill, Susan Michie, Robert West
Journal: Thorax (2015)

<h3>Background</h3> The rise in electronic cigarette use by smokers may be responsible for the decreased use of licensed nicotine products and/or increased overall use of non-tobacco nicotine-containing products. This paper reports findings from the Smoking Toolkit Study (STS) tracking use of electronic cigarettes and licensed nicotine products to address this issue. <h3>Methods</h3> Data were obtained from monthly surveys involving 14 502 cigarette smokers in England between March 2011 and November 2014. Smokers were asked about their use of electronic cigarettes and licensed nicotine products. <h3>Results</h3> Prevalence of electronic cigarette use increased rapidly from 2.2% (95% CI 1.4% to 3.2%) in quarter 2 of 2011 to 20.8% (95% CI 18.3% to 23.4%) in quarter 3 of 2013, after which there was no change. Prevalence of licensed nicotine product use in smokers remained stable from quarter 2 of 2011 (17.4%, 95% CI 15.3% to 19.8%) to quarter 3 of 2013 (17.9%, 95% CI 15.62% to 20.5%), and thereafter declined steadily to 7.9% (95% CI 6.0% to 10.4%). Prevalence of use of any product was stable to quarter 1 of 2012, after which it increased from 18.5% (95% CI 16.3% to 21.0%) to 33.3% (95% CI 30.4% to 36.3%) in quarter 3 of 2013, and then decreased to 22.7% (95% CI 19.3% to 26.3%). <h3>Conclusions</h3> The shapes of trajectories since 2011 suggest that electronic cigarettes are probably not responsible for the decline in use of licensed nicotine products. Electronic cigarettes appear to have increased the total market for use of non-tobacco nicotine-containing products.
Fundamentals of Aerospace Medicine.
Authors: Roy L. DeHart
Journal: Annals of Internal Medicine (1988)

Part 1 Aerospace medicine in perspective: historical, modern and future perspectives. Part 2 Physiology in the flight environment: the atmosphere respiratory physiology protection in the pressure environment decompression sickness and pulmonary overpressure accidents biodynamics vibration, noise and communication spatial orientation in flight thermal stress beyond the biosphere. Part 3 Clinical practice of aerospace medicine: aircrew health care maintenance clinical aerospace cardiovascular and pulmonary medicine ophthalmology, otolaryngology, neuropsychiatry in aerospace medicine the passenger and patient in flight. Part 4 Operational aerospace medicine: army aviation medicine naval aerospace medicine civil aviation medicine international aviation medicine aircraft accident investigation human factors in aerospace medicine biomedical challenges of spaceflight aircraft accidents - prevention, survival and rescue. Part 5 Impact of the aerospace industry on community health: role of aviation in the transmission of disease aviation and the environment. (Part contents).
More centralisation of services is not needed
Authors: B. Sizer, S. Karp
Journal: BMJ (1996)

EDITOR,—Charles R Gillis and David J Hole may have found evidence that survival of patients with breast cancer is improved if they are treated by specialist breast surgeons, but there is little scientific evidence that surgery influences survival from breast cancer to any significant extent and they collected no information on the details of treatment received.1 There is considerable evidence, however, to support the survival …
Prognostic Relevance of Imaging Bone Metastases By Whole Body Diffusion-Weighted Magnetic Resonance Imaging (Wbdwi) in Metastatic Castration-Resistant Prostate Cancer (Mcrpc)
Authors: R. Perez Lopez, D. Lorente, J. Mateo, M.D. Blackledge, S. Sideris, Z. Zafeiriou, A. Smith, R. Ferraldeschi, P. Rescigno, M. Rata, U. Naumann, D.J. Collins, G. Attard, M.O. Leach, D. Koh, J.S. de Bono, N. Tunariu
Journal: Annals of Oncology (2014)
Cough hypersentivity syndrome: Preliminary findings of the ERS taskforce
Authors: Alyn Morice, Kian Fan Chung, Peter Dicpinigaitis, Lorcan McGarvey, Eva Millqvist, Raimundas Sakalauskas, Kristina Stravinskaite, Adalberto Pacheco, Surinder Birring, Jacky Smith, Maria Belvisi, Lieven Dupont, Ami Kantar, Roberto Del Negro
Journal: European Respiratory Journal (2013)

The ERS Taskforce on the Diagnosis and Classification of Chronic Cough performed a survey of 44 key opinion leaders across the range of respiratory medicine. Questions had been constructed following a modified Delphic process at Task Force meetings. 21 questions were constructed concerning cough hypersensitivity syndrome and its diagnosis, the pathobiology of cough reflex sensitivity and the treatment of the condition. In conjunction with the European Lung Foundation questions were devised on quality of life and the resources available for patients.  There was strong unanimity of opinion within the respiratory community with all but one correspondent agreeing the cough hypersensitivity syndrome was an important clinical syndrome which may co-exist with other respiratory conditions. It was thought to be distinct from asthma and upper airways disease. Steroid responsive cough was thought to be strongly associated with eosinophilic inflammation but this was considered to be a subset of cough hypersensitivity syndrome. Cough in children was considered to be different from adult cough by 20 of 44 correspondents. The under recognition of the impact of cough on quality of life and lack of resources for cough management were overwhelmingly indicated.
The British Association of Dermatologists’ Biologic Interventions Register (BADBIR): design, methodology and objectives
Authors: A.D. Burden, R.B. Warren, C.E. Kleyn, K. McElhone, C.H. Smith, N.J. Reynolds, A.D. Ormerod, C.E.M. Griffiths
Journal: British Journal of Dermatology (2012)

The British Association of Dermatologists (BAD) established a web-based pharmacovigilance register to assess the long-term safety of biologics prescribed for patients with severe psoriasis in September 2007. The BAD Biologic Interventions Register (BADBIR) also participates in the network of European psoriasis biologics registers (Psonet).This prospective observational cohort study compares adult patients with psoriasis treated with biologics vs. a comparator group exposed to conventional systemic therapies.Following baseline data acquisition, clinicians record changes in therapy, disease activity and adverse events for 5years (6-monthly for 3years, then annually thereafter). Patient details are flagged lifelong on the National Health Service Information Centre system to capture occurrence of malignancy or death. Primary study endpoints include malignancy, infection, serious adverse events and death. Collection of long-term effectiveness data is a subsidiary aim.By November 2011, the number of dermatology centres actively recruiting across the U.K. and Republic of Ireland had risen to 108 and a further 37 were actively engaged in the set-up process. Of the 3176 patients enrolled in the study to date, 2193 were registered within the biologic cohort and 983 in the conventional systemic (nonbiologic-exposed) cohort.A robust, high-quality, web-based register of biologic and conventional therapy for psoriasis has been established in the U.K. This is the largest project undertaken by the BAD. The data it will provide over the coming years will be invaluable to the safe use of biologics in clinical practice. A U.K.-wide dermatology clinical research network has been established that provides a framework for future studies in other diseases.
Optimizing Therapy for Acute Myeloid Leukemia
Authors: Holbrook E. Kohrt, Steven E. Coutre
Journal: Journal of the National Comprehensive Cancer Network (2008)

The 10-year overall survival for younger patients with newly diagnosed acute myeloid leukemia has improved threefold in the past 2 decades. This improvement has occurred in large part because of advances in supportive care and efforts to optimize standard induction and consolidation therapies applied in a stratified approach based on predictors of individual patient risk. Innovations in diagnostic technologies have broadened the understanding of key prognostic factors, including cytogenetic and molecular status, which define the extensive interpatient heterogeneity of this clonal disease. Despite this progress, only approximately 25% of patients who experience a complete remission with cytotoxic chemotherapy (50%–70% of patients with newly diagnosed disease) remain disease-free. Efforts to develop novel agents are actively ongoing, particularly for older patients (age ≥ 60), and targeted therapies, for specific subsets of patients are being based on a better understanding of the biology of the disease.
A Prospective Randomized Study of Hydrophilic Polymer-Coated Polyurethane Versus Polyethylene Stents in Distal Malignant Biliary Obstruction
Authors: A M van Berkel, M J Bruno, J J G H M Bergman, S J van Deventer, G N J Tytgat, K Huibregtse
Journal: Endoscopy (2003)

Background and Study Aims: Hydrophilic polymer-coated polyurethane (HPCP) stents have a low friction coefficient and a hydrophilic layer, which may reduce biofilm formation and increase the period of stent patency. We compared the patency rates with this new stent with the standard Amsterdam-type polyethylene (PE) stent in a prospective randomized trial. Patients and Methods: One hundred patients with an unresectable distal malignant bile duct stricture without a previous drainage procedure were randomly assigned to receive either a HPCP stent or a PE stent. The diameter (10 Fr), length (9 cm) and stent design (Amsterdam type) were similar in both stents. Nine patients were excluded. Forty-four patients received an HPCP stent and 47 patients a PE stent. The diagnoses included carcinoma of the pancreas (n = 78), papilla (n = 1), bile duct (n = 10), and metastases (n = 2).
Phase I Trial of Escalating Doses of Paclitaxel Plus Doxorubicin and Dexrazoxane in Patients With Advanced Breast Cancer
Authors: Joseph A. Sparano, James Speyer, William J. Gradishar, Leonard Liebes, Rajeshwari Sridhara, Sandra Mendoza, David Fry, Merrill J. Egorin
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To determine the maximum-tolerable dose (MTD) of paclitaxel given as a 3-hour intravenous (IV) infusion that could be used in conjunction with doxorubicin and dexrazoxane, and to determine the effect of dexrazoxane on the pharmacokinetics of paclitaxel and doxorubicin. PATIENTS AND METHODS: Twenty-five patients with advanced breast cancer received dexrazoxane (600 mg/m 2 by IV infusion over 15 minutes), followed 15 minutes later by doxorubicin (60 mg/m 2 IV), followed 15 minutes later by paclitaxel (150 or 175 mg/m 2 by IV infusion over 3 hours) in cohorts of three to six patients using a standard phase I design without (group A) and with (group B) granulocyte colony-stimulating factor (G-CSF). Treatment continued until there was a substantial decrease in the left ventricular ejection fraction (LVEF), congestive heart failure, progressive disease, or physician discretion to discontinue. RESULTS: The MTD of paclitaxel was 150 mg/m 2 , and adjunctive therapy with G-CSF was required to prevent febrile neutropenia. Dexrazoxane had no significant effect on the pharmacokinetics of paclitaxel or doxorubicin. After a median cumulative doxorubicin dose of 360 mg/m 2 (range, 60 to 870 mg/m 2 ), no patient developed congestive heart failure or had a decrease in LVEF below normal. An objective response occurred in all five patients with locally advanced breast cancer and in eight of 20 patients (40%; 95% confidence interval, 19% to 61%) with metastatic breast cancer. CONCLUSION: When combined with doxorubicin (60 mg/m 2 ) and dexrazoxane (600 mg/m 2 ), paclitaxel given as a 3-hour infusion had an MTD of 150 mg/m 2 , and G-CSF was required to prevent febrile neutropenia. Dexrazoxane had no effect on the pharmacokinetics of paclitaxel or doxorubicin. No patient in this trial had a decrease in the LVEF below normal, compared with about 20% to 50% of patients treated with doxorubicin and paclitaxel without dexrazoxane in other trials.
Theoretical foundation of the minimum-evolution method of phylogenetic inference.
Authors: A Rzhetsky, M Nei
Journal: Molecular Biology and Evolution (1993)

The minimum-evolution (ME) method of phylogenetic inference is based on the assumption that the tree with the smallest sum of branch length estimates is most likely to be the true one. In the past this assumption has been used without mathematical proof. Here we present the theoretical basis of this method by showing that the expectation of the sum of branch length estimates for the true tree is smallest among all possible trees, provided that the evolutionary distances used are statistically unbiased and that the branch lengths are estimated by the ordinary least-squares method. We also present simple mathematical formulas for computing branch length estimates and their standard errors for any unrooted bifurcating tree, with the least-squares approach. As a numerical example, we have analyzed mtDNA sequence data obtained by Vigilant et al. and have found the ME tree for 95 human and 1 chimpanzee (outgroup) sequences. The tree was somewhat different from the neighbor-joining tree constructed by Tamura and Nei, but there was no statistically significant difference between them.
Preparing asthmatic patients to climb to extreme high altitude (asthma Aconcagua expedition)
Authors: Sven Seys, Marc Daenen, Lieven Dupont
Journal: European Respiratory Journal (2011)

A group of 18 asthmatics were evaluated in preparation for an expedition to climb the Aconcagua mountain (6900m).  Patients were evaluated at different time points before expedition: screening visit, hypoxia chamber and cold air exposition (in an attempt to simulate conditions at extreme altitude) as well as before/after the expedition. During the hypoxia simulating experiment, patients stayed for 30 min in a chamber filled with 11% of oxygen followed by a maximal exercise test. During the cold air exposition, patients resided for 24 hours in an indoor ski resort (mean temperature of -8 °C).  All patients except one (score of 18/25) had an ACT well controlled asthma (ACT > 20). During one year of preparation, FeNO values significantly reduced (p=0.01) while lung function parameters remained stable. FEV1 and FeNO values were slightly but significantly lower (mean change in%pred FEV1 of 2.7%, p=0.01 and mean change in FeNO of 2.2 ppb, p=0.03) after a maximal exercise protocol under hypoxic conditions (FiO2=11%). A significant decrease in FEV1 was also observed after a 24h stay at -8 °C (mean change of 6.6%, p=0.009). This was accompanied by an increase in sputum neutrophils (13% pre versus 48.6% post, p  During one year of preparation prior to climbing the Aconcagua mountain, there was an improvement in airway inflammation despite adequate asthma control at baseline. Exercising in hypoxic conditions (60 min, FiO2 11%) induced a minor decrease in FEV1 and FENO in asthmatics. Exposure of asthmatic patients to cold air for 24hr resulted in a larger decrease in FEV1, which was associated with a neutrophilic airway inflammation.
Effects of Gonadectomy on Foreign-Body Tumorigenesis in CBA/H Mice<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>
Authors: V J Michelich, K G Brand
Journal: JNCI Journal of the National Cancer Institute (1980)

Sarcomas were induced by sc implantation of unplasticized polyvinylchloride-vinylacetate films in gonadectomized and normal male and female CBA/H mice. Gonadectomy did not demonstrably influence tumor incidence and tumor latencies in males but significantly prolonged tumor latencies in females. The results suggest that estrogen influences the pace of foreign-body tumorigenesis in CBA/H mice.
Cytokine response in the lungs, pleural fluid and serum in children after thoracic surgery using one- lung ventilation
Authors: Dmytro Dmytriiev, Oleksander Katilov, Oleksander Mazulov, Kateryna Dmytriieva
Journal: European Respiratory Journal (2012)

Thoracic surgery mandates usually a one-lung ventilation (OLV) strategy with the collapse of the operated lung and ventilation of the non-operated lung. These procedures trigger a substantial inflammatory response. The aim of this study was to analyze the cytokine reaction in both lungs, pleural space and blood in patients undergoing lung resection with OLV.  METHODS: Broncho-alveolar lavage (BAL) fluid of both the collapsed, operated and the ventilated, non-operated lung, respectively, pleural space drainage fluid and blood was collected and the concentrations of interleukin (IL)-6, IL-1RA were determined with enzyme-linked immunosorbent assays in 24 patients.  RESULTS: Substantial inter-individual differences in the BAL fluid between patients in cytokine levels occurred. In the pleural fluid and the blood these inter-individual differences were less pronounced. Both sides of the lung were affected and showed a significant increase in IL-6 (14.2 +/- 2.2 and 1.8 +/- 0.7 pg/mL (mean +/- se) and IL-1RA (23.2 +/- 1.7 and 4.2 +/- 2.6 pg/mL (mean +/- se) concentrations over time in the children with one-lung ventilation (OLV) and non one-lung ventilation (p   CONCLUSION: The inflammatory response of cytokines affects both the collapsed, operated and the ventilated, non-operated lungs. The difference in extent of response underlines the complexity of the inflammatory processes during OLV In contrast to the cytokines.
Phantom bite syndrome
Authors: J J Marbach
Journal: American Journal of Psychiatry (1978)

Despite repeated treatment failures, some individuals seek bite correction from a succession of dentists. Their pathological narcissism focuses on their bite, in a manner reminiscent of phantom limb phenomena. The dentist's diagnosis and treatment are manipulated until the patient claims them a failure and consults another dentist. The author suggests that this behavior represents a defense against paranoia and severe personality disorders.
Comparison of PTEN protein loss and PI3K gene mutation status in breast cancer
Authors: Arnold B. Gelb, Lynn Deng, Vicki A. Freeman, Stephanie H. Astrow
Journal: Clinical Cancer Research (2010)

Abstract Background: The phosphatidylinositol 3-kinase (PI3K) family of enzymes plays key roles in the transduction of cell signals, and several inhibitors of this pathway are currently in clinical development for the treatment of breast and other cancers. PI3K signaling is activated by growth factor receptors and regulated and terminated by multiple factors including dephosphorylation of the 3′ phosphate of PIP3 by the phosphatase PTEN. Reduced PTEN expression in breast cancer confers susceptibility to inhibitors of the PI3 kinase/Akt pathway. In a subset of breast cancer cases, PTEN protein has been found to be expressed at lower levels (e.g., as compared with normal breast epithelium), however, human breast cancer cells rarely have PTEN mutations. On the other hand PI3K gene mutations have been found in a majority of breast tumors. Methods: To examine the relationship between PTEN protein loss and PI3K gene mutation, PTEN immunoreactivity was assessed semi-quantitatively using histoscores in freshly-cut sections of paraffin blocks from 26 anonymized breast cancer specimens. Sections from the same tumor blocks were used for PI3K mutation detection. One H&amp;E-stained section was used to mark the area of tumor and 2-4 additional unstained sections were macrodissected to enrich for tumor cells, which then underwent DNA extraction. The DNA was analyzed with a commercial PI3K mutation test kit (DxS PI3K Mutation Test Kit, Manchester, UK) that detects 4 somatic mutations in exons 9 and 20 of PIK3CA in three discrete mutation groups or “buckets.” Results: Of the 26 breast cancer specimens examined, 7 (27%) had absence of PTEN protein expression (histoscore=0) and an additional 4 (15%) had a reduction in PTEN expression (histoscore&amp;gt;0 to &amp;lt;50), with positive internal controls. PI3K mutations were detected in 8 (31%) of the 26 breast cancer specimens examined. Of the mutations detected, there were 4 (15%) mutations of H1047R (3140 A&amp;gt;G), 1 (4%) of E542K (1624 G&amp;gt;A), and 3 (12%) of E545D (1635 G&amp;gt;T) or E545K (1633 G&amp;gt;A). Conclusions: There was a statistically significant correlation between PTEN loss (histoscore&amp;lt;50) and the detection of PI3K mutations (Fisher's exact test, 2-tail P=0.003). The percentage of cases with overall PTEN loss in this specimen set was similar to previous reports of PTEN loss in breast tumors. In contrast, another report did not find concomitant PTEN loss and PI3K mutations. However, the investigators evaluated fewer samples, studied HER2 amplified breast cancer specifically, and used a different method (sequencing) to detect mutations. A three-way study that includes HER2 amplification or overexpression may be necessary to explain the discrepancy.