tbuckley/cabot-search huggingface dataset:
Revisiting the commercial-academic interface in medical journals
Authors: E. Loder, C. Brizzell, F. Godlee
Journal: BMJ (2015)

The New England Journal of Medicine goes on an ill advised journey

Public trust in the pharmaceutical and biotechnology industry is low.1 Many practising physicians share that mistrust and are inclined to discount the results of otherwise sound studies that are industry funded.2 3 There are good historical reasons to be sceptical. But has suspicion degenerated, as some have charged, into “mindless demonisation?”4 The New England Journal of Medicine ( NEJM ) seems to think so. It has published a series of commentaries and an editorial suggesting there have been serious negative consequences of strict, “oversimplified” conflict of interest and disclosure policies, including the development of a “hostile climate” and “loss of trust.”5 6 7 8 Editor in chief, Jeffrey Drazen, says the “divide” between academic researchers and industry is not in the best interests of the public because “true improvement can come only through collaboration.”

A close reading of Drazen’s editorial suggests he is having second thoughts about policies put in place by many journals—including The BMJ —that make it “harder and harder for people who have received industry payments or items of financial value to write editorials or review articles . . . …
Ethnicity and stratum corneum ceramides
Authors: J.M. Jungersted, J.K. Høgh, L.I. Hellgren, G.B.E. Jemec, T. Agner
Journal: British Journal of Dermatology (2010)

The barrier function of the skin is dependent on an optimal composition of the stratum corneum lipids, exemplified by the altered lipid profile in patients with atopic eczema (AE). Differences in the global prevalence of AE point to the environment as an important factor in AE. Studies on filaggrin point to a genetic aspect in AE. The influence of environment and genes needs to be explored.To investigate possible differences in stratum corneum lipids between different healthy ethnicities living in the same environment.Healthy participants without any major skin diseases were enrolled in the study. Twenty-five participants of Asian origin (Asians), 18 of African origin (Africans) and 28 of Danish origin (white-skinned), all students at universities in the Copenhagen area of Denmark, had the ceramide profile of their stratum corneum examined using the cyanoacrylate method and analysed using high-performance thin layer chromatography.For the ceramide/cholesterol ratio we found statistically significant differences between groups, with Asians having the highest ratio (P < 0·001 as compared with both white-skinned individuals and Africans), white-skinned individuals having intermediate values, and Africans having the lowest values. No statistically significant differences were found between any of the ceramide subgroups.We found different ceramide/cholesterol ratios in comparable groups of different ethnicity, pointing to unknown genetic differences.
Effects of celiprolol, a cardioselective beta-blocker, on respiratory function in asthmatic patients
Authors: J C Pujet, C Dubreuil, B Fleury, O Provendier, M L Abella
Journal: European Respiratory Journal (1992)

The aim of this study was to compare the pulmonary effects of a single dose of celiprolol 400 mg, versus bisoprolol 20 mg and the combination of celiprolol 400 mg plus propranolol 40 mg versus placebo plus propranolol 40 mg. We conducted a double-blind randomized cross-over study in 10 stable asthmatic patients (mean age +/- SD 31 +/- 7 yrs) with forced expiratory volume in one second (FEV1): 2.5 +/- 0.7 l. A three-day washout period preceded each treatment period. Measurements of respiratory function were done before treatment and after 90, 120 and 180 min. There was a significant increase of FEV1 (+12%) and forced vital capacity (FVC) (+8%) after celiprolol (p less than 0.05) and a decrease of FEV1 (-9%) after propranolol. Concerning the combination, celiprolol inhibits the bronchoconstrictor effects of propranolol. We conclude that celiprolol has bronchosparing properties in asthmatic patients, and even improves some of the ventilatory parameters.
Comparison of serial rapid shallow breathing index to serial CROP index in prediction of weaning outcome in critical care patients
Authors: Angelene Taleon-Parazo, Lucas Uy
Journal: European Respiratory Journal (2013)

Background :Recent data comparing several weaning parameters (RSBI,Cdyn,CStat,Pimax,CROP) concluded that CROP index has the highest predictive power for weaning outcome. It is the purpose of this study to compare serial RSBI with CROP in predicting weaning outcome.

Methodology: This is a Prospective Cohort study done in the Philippine Heart Center Critical Care units done from December 2011-November 2012 . Patients aged >18yo on mechanical ventilator for >48hours and capable of being weaned.RSBI and serial CROP index was taken 30 minutes, 60minutes and 120minutes pre-extubation. ABG was taken at the of each cycle. Extubation is considered a success if patient is able to sustain spontaneous breathing for >48 hours.

Results: There was a total of 56patients, in the study.It was observed that increasing trend of CROP predicted weaning success while increasing RSBI was related to weaning failure. There were 5patients who were bridged with NIV. These patients had low CROPscores. This maybe due to critical illness myopathy. Cut off value for both parameters were determined and revealed a sensitivity 72.1% and specificity 76.9% for CROP≥0.1. RSBI value≥ 53 had 67.4% sensitivity and 69.2% specificity. AUC yielded 0.6 for RSBI and 0.7 for CROP having a greater value is more predictive.

Conclusion: Trends of weaning parameters can detect subtle changes in respiratory endurance. An increasing RSBI was noted in weaning failures. Conversely, an increasing CROP can predict weaning success. In this study, RSBI has 67.4% sensitivity and 69.2% specificity compared to CROP with sensitivity 72.1% and specificity 76.9%. CROP is a better predictor for weaning success.
Small moleculae ACE2 activator, diminazene aceturate attenuates bleomycin-induced pulmonary fibrosis
Authors: Vinayak Shenoy, Yanfei Qi, Dipankar Gupta, Michael Katovich, Mohan Raizada
Journal: European Respiratory Journal (2012)

INTRODUCTION:  Angiotensin Converting Enzyme2 (ACE2), a member of the renin angiotensin system has been shown to render protection against lung diseases, particularly pulmonary fibrosis (PF). In this study, we investigated the effects of a recently identified synthetic activator of ACE2, Diminazene aceturate (DIZE) against bleomycin-induced PF.   METHODS:  A single intratracheal instillation of bleomycin (Bleo, 5U/Kg) in 8-week old male rats induced PF. Animals were randomized into Control, Bleo and Bleo+DIZE groups. DIZE treatment (15mg/Kg, sc) was commenced soon after bleomycin administration. Following 14 days of bleomycin instillation, right ventricular systolic pressure (RVSP) was measured, followed by heart and lung excision to examine cardiopulmonary remodeling.   RESULTS:  Control rats exhibited a weight gain of 35%, while bleomycin-challenged animals lost 10% of their initial body weight by the end of the study period. Conversely, Bleo+DIZE group demonstrated 16% weight gain. Furthermore, Bleo animals displayed marked elevation in RVSP (Control: 27±1; Bleo: 40±2 mmHg; p   CONCLUSION:  Collectively, our results suggest that DIZE prevents bleomycin-induced lung fibrosis and improves cardiopulmonary hemodynamics. Thus, DIZE treatment may represent a promising therapeutic strategy for treating PF.
Genetic Analysis of Association Between Calcium Signaling and Hippocampal Activation, Memory Performance in the Young and Old, and Risk for Sporadic Alzheimer Disease
Authors: Angela Heck, Matthias Fastenrath, David Coynel, Bianca Auschra, Horst Bickel, Virginie Freytag, Leo Gschwind, Francina Hartmann, Frank Jessen, Hanna Kaduszkiewicz, Wolfgang Maier, Annette Milnik, Michael Pentzek, Steffi G. Riedel-Heller, Klara Spalek, Christian Vogler, Michael Wagner, Siegfried Weyerer, Steffen Wolfsgruber, Dominique J.-F. de Quervain, Andreas Papassotiropoulos
Journal: JAMA Psychiatry (2015)

Human episodic memory performance is linked to the function of specific brain regions, including the hippocampus; declines as a result of increasing age; and is markedly disturbed in Alzheimer disease (AD), an age-associated neurodegenerative disorder that primarily affects the hippocampus. Exploring the molecular underpinnings of human episodic memory is key to the understanding of hippocampus-dependent cognitive physiology and pathophysiology.
An H1-histamine receptor antagonist decreases serum interleukin-31 levels in patients with atopic dermatitis
Authors: A. Otsuka, T. Honda, H. Doi, Y. Miyachi, K. Kabashima
Journal: British Journal of Dermatology (2010)

Funding sources: none. Conflicts of interest: none declared. Madam, Atopic dermatitis (AD) is an intractable inflammatory skin disease characterized by an intensely pruritic skin rash with a typical morphology and distribution in accordance with an impaired skin barrier. Pruritus in AD affects quality of life and is sometimes difficult to control. There is a wide variety of mediators of pruritus, including histamine, neuropeptides, prostaglandins, serotonin and bradykinin. It has recently been reported that interleukin (IL)‐31, a 4‐helix‐bundle cytokine, is a new candidate of itch mediator, preferentially produced by T cells skewed toward Th2.1 Transgenic mice overexpressing IL‐31 spontaneously developed severe pruritus, resulting in eczematous skin lesions with hyperkeratosis, acanthosis and inflammatory cell infiltration, which closely resembled those of AD.1 Leucocytes in patients with AD expressed significantly higher IL‐31 levels compared with those of control subjects.2 In addition, IL‐31 levels correlate with disease activity in AD.3 Epinastine is an H1‐histamine receptor antagonist that is widely used throughout the world (18 countries). As epinastine is known to inhibit the development of Th2 immune responses,4 it is of interest to evaluate the effect of epinastine on IL‐31 expression. In this study, we have evaluated the effect of epinastine on serum IL‐31 levels in patients with AD in line with pruritus.
Effect of Continuous Positive Airway Pressure on Sleep Architecture in the Sleep Apnea–Hypopnea Syndrome
Authors: NIGEL McARDLE, NEIL J. DOUGLAS
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

There is randomized controlled evidence that patients with sleep apnea–hypopnea syndrome (SAHS) treated with continuous positive airway pressure (CPAP) have improved daytime function and quality of life. “Before-and-after” data indicate that CPAP improves sleep quality, but there is no randomized controlled evidence of this. We tested the hypothesis that CPAP improved sleep quality in patients with SAHS. We also sought correlations between polysomnographic (PSG) indices and benefit from use of CPAP. Twenty-two patients with SAHS (median, [interquartile range] apnea–hypopnea index, 40 [25–65] events/h) spent 1 mo receiving CPAP and 1 mo receiving placebo capsules, in random order, and home sleep studies were performed at the end of each month. CPAP resulted in a lower arousal index, less Stage 1, and more Stage 3 + 4 sleep, but there was no increase in Stage REM (rapid eye movement) sleep. Improvement in Epworth score after 6–12 mo of treatment correlated significantly with PSG indices on CPAP: sleep efficiency index (r = 0.78, p < 0.001), Stage REM (r = 0.55, p = 0.001), Stage 3 + 4 (r = 0.5, p = 0.02), and arousal index (r = − 0.43, p = 0.05). This study provides randomized controlled trial evidence that patients with SAHS sleep better when receiving CPAP. Patients with good sleep quality on CPAP at 1 mo are likely to gain later benefit in subjective daytime sleepiness.
High-dose intravenous methotrexate for patients with nonleukemic leptomeningeal cancer: is intrathecal chemotherapy necessary?
Authors: M J Glantz, B F Cole, L Recht, W Akerley, P Mills, S Saris, F Hochberg, P Calabresi, M J Egorin
Journal: Journal of Clinical Oncology (1998)

PURPOSE Standard treatments for neoplastic meningitis are only modestly effective and are associated with significant morbidity. Isolated reports suggest that concurrent systemic and intrathecal (i.t.) therapy may be more effective than i.t. therapy alone. We present our experience, which includes CSF and serum pharmacokinetic data, on the use of high-dose (HD) intravenous (i.v.) methotrexate (MTX) as the sole treatment for neoplastic meningitis. PATIENTS AND METHODS Sixteen patients with solid-tumor neoplastic meningitis received one to four courses (mean, 2.3 courses) of HD (8 g/m2 over 4 hours) i.v. MTX and leucovorin rescue. Serum and CSF MTX concentrations were measured daily. Toxicity, response, and survival were retrospectively compared with a reference group of 15 patients treated with standard i.t. MTX during the same time interval. RESULTS Peak methotrexate concentrations ranged from 3.7 to 55 micromol/L (mean, 17.1 micromol/L) in CSF and 178 to 1,700 micromol/L (mean, 779 micromol/L) in serum. Cytotoxic CSF and serum MTX concentrations were maintained much longer than with i.t. dosing. Toxicity was minimal. Cytologic clearing was seen in 81% of patients compared with 60% of patients treated intrathecally (P = .3). Median survival in the HD i.v. MTX group was 13.8 months versus 2.3 months in the i.t. MTX group (P = .003). CONCLUSION HD i.v. MTX is easily administered and well tolerated. This regimen achieves prolonged cytotoxic serum MTX concentrations and CSF concentrations at least comparable to those achieved with standard i.t. therapy. Cytologic clearing and survival may be superior in patients treated with HD i.v. MTX. Prospective studies and a reconsideration of the use of i.t. chemotherapy for patients with neoplastic meningitis are warranted.
Mammary Carcinogenesis by 3-Methylcholanthrene. IV. Effect of Pituitary Homograft on Mammary-Gland Growth and Tumorigenesis&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Thomas L. Dao
Journal: JNCI Journal of the National Cancer Institute (1962)

Single pituitary homografts were transplanted subcutaneously into intact female, castrated female, intact male, and orchiectomized male rats subsequently treated with optimal carcinogenic dose of 3-methylcholanthrene (3-MCA). In intact females, a functioning pituitary graft maintained functioning corpora lutea and caused milk secretion. In castrated female, intact male, and castrated male rats, the pituitary graft stimulated the growth of the mammary glands. One of the most significant observations was that prolactin released by the pituitary graft exerted a direct action on the growth of the mammary gland and that this function was independent of the presence or absence of the ovaries and pituitaries. Prolactin released by the pituitary graft, however, had little or no effect on the induction of mammary cancer in these rats when they were treated with 3-MCA. Multiple pituitary grafts (2 to 4) in castrated male rats induced “lactation” but did not increase tumor incidence. It is concluded that the pituitary hormones, especially the lactogenic hormones, involved in mammary-gland growth may not be needed in the development of mammary tumors in 3-MCA treated rats.
Randomized trial of r-metHu granulocyte colony-stimulating factor in an intensive treatment for T-cell leukemia and advanced-stage lymphoblastic lymphoma of childhood: a Pediatric Oncology Group pilot study.
Authors: J Laver, M Amylon, S Desai, M Link, M Schwenn, H Mahmoud, J Shuster
Journal: Journal of Clinical Oncology (1998)

PURPOSE Contemporary chemotherapy has significantly improved the event-free survival (EFS) among patients with T-cell disease. However, myelosuppression has been a significant adverse effect of this approach. In this study, we assessed the impact of r-metHu granulocyte colony-stimulating factor (G-CSF) on the period of neutropenia, number of days of hospitalization, and delays in subsequent administration of chemotherapy in a cohort of patients with T-cell leukemia (T-ALL) or advanced stage lymphoblastic lymphoma (ASLL). PATIENTS AND METHODS This open-label, randomized trial incorporated r-metHuG-CSF into the induction and two consecutive continuation-therapy cycles of our intensive program for T-cell malignancies. In the induction phase, r-metHuG-CSF was given after two different combinations of chemotherapy, one of which included vincristine, prednisone, cyclophosphamide, and adriamycin and the other a continuous infusion of high-dose ara-C and L-asparaginase. In the two continuation-therapy cycles, r-metHuG-CSF was given following the combination of vincristine, adriamycin, prednisone, and 6-mercaptopurine (MP) and after continuous infusion of high-dose cytarabine (ara-C). RESULTS Fifty-six patients with T-ALL and 33 with ASLL were enrolled onto study from April 1994 to December 1995. Our data show no significant difference in number of days of absolute neutrophil count (ANC) less than 500/microL, hospitalizations, or delays in therapy in the induction phase. However, in the continuation-therapy phase the number of days of ANC less than 500/microL was significantly shorter (P = .017) on the G-CSF-arm without significantly affecting the number of days of hospitalizations or delays in therapy. CONCLUSION r-metHuG-CSF did not significantly affect the period of neutropenia, hospitalization, or delays in therapy in the induction phase, whereas in the two cycles of continuation therapy, it significantly shortened the period of neutropenia.
LSC 2013 abstract - Lung-resident CD4+T cells are sufficient for IL-4Rα dependent recall immunity to nippostrongylus brasiliensis infection
Authors: Sumaiyya Thawer, William Horsnell, Matthew Darby, Jennifer Hoving, Benjamin Dewals, Antony Cutler, Frank Brombacher
Journal: European Respiratory Journal (2013)

Murine reinfection studies with the parasitic nematode  Nippostrongylus brasiliensis  have shown development of T helper 2 (T H 2) CD4 +  T cell responses in the lung to be essential for immunity to secondary  N. brasiliensis  infection. We examined if secondary lymphoid recruited or lung-resident CD4 +  T cell populations coordinated this immunity.  Fingolimod (FTY720) blocking of T cell egress from lymph nodes (LN) to peripheral tissues impaired host ability to resolve a primary infection, but did not effect recall immunity. A pre-existing pulmonary CD4 +  T cell population with increased expression of the T H 2 associated T1/ST2 receptor and heightened parasite specific T H 2 cytokine responses in the lung was associated with this protective immunity. Adoptive transfer of  N. brasiliensis  experienced pulmonary CD4 +  T cells from FTY720 treated wild type and T cell IL-4Ra deficient mice demonstrated this protection to be IL-4Rα dependent.  These results establish that lung-resident CD4 + T cells can drive effective recall immunity to  N. brasiliensis  independently of T cell recruitment from secondary lymphoid organs.
Analysis of clinically theranostic relevant genes, EGFR and KRAS, in subtypes of non-small cell lung cancer (NSCLC) patients
Authors: Melanie Demes, Holger Bartsch, Scheil-Bertram Stefanie, Schirren Joachim, Bölükbas Servet, Frickhofen Norbert, Fisseler-Eckhof Annette
Journal: European Respiratory Journal (2011)

Aims:  KRAS  and  EGFR  oncogenes have proven to be clinically significant as predictive or prognostic factors in non-small cell lung cancer (NSCLC). These genetic alterations are poorly investigated in squamous cell carcinoma (SCC).  In a single study we evaluated the frequency of these cancer relevant genes in adenocarcinoma (ADC) and SCC and therefore sought to gain further inside into the significance of  EGFR  in NSCLC and to explore whether these mutations are restricted to an adenocarcinoma component.   Materials and methods:  Tumor samples of 741 patients suffering from stage III to IV NSCLC were investigated.  KRAS  mutations were examined by means of two independent analytical methods (Sequencing and SNaPshot). The molecular status of  EGFR exon 19  and  exon 21  were analyzed by fragment analysis. Mutations in  EGFR exon 18  were assayed by direct sequencing.   Results:  The 741 NSCLC samples comprised 149 (20.1%) SCC and 592 (79.9%) ADC. No coexisting mutations of  EGFR  and  KRAS  occurred in ADC and SCC, respectively.  EGFR  mutations were detected in 9 of 149 (6%) SCC (5.4% in  exon 21  and 0.6% in  exon 19 ) and in 110 of 592 (18.6%) ADC (9.1% in  exon 19 , 8.8% in  exon 2  1 and  exon 18 ).  7 of 95 (7.4%) SCC and 79 of 243 (32.5%) ADC were characterized as  KRAS -mutation positive.   Conclusion:  In conclusion somatic mutations of  EGFR  and  KRAS  gene can also develop in SCC. Patients with  EGFR  mutations are thus considered candidates for chemotherapeutic treatment targeting  EGFR . Therefore  EGFR  mutational analysis should be performed not only in ADC, but also in SCC to allow accurate diagnosis and treatment.
Similarities Suggest a Shared Embryologic Origin for Pancreatic and Ovarian Mucinous Tumors
Authors: I. Labidi-Galy, K.M. Elias, A.F. Vitonis, J.L. Hornick, L.A. Doyle, M.S. Hirsch, D.W. Cramer, R. Drapkin
Journal: Annals of Oncology (2014)
Paroxysmal nocturnal hemoglobinuria induced by the occurrence of BCR-ABL in a PIGA mutant hematopoietic progenitor cell
Authors: R Tominaga, T Katagiri, K Kataoka, K Kataoka, R K C Wee, A Maeda, H Gomyo, I Mizuno, T Murayama, S Ogawa, S Nakao
Journal: Leukemia (2015)
ESPAC-3(v2): A multicenter, international, open-label, randomized controlled phase III trial of adjuvant 5-fluorouracil/folinic acid (5-FU/FA) versus gemcitabine (GEM) in patients with resected pancreatic ductal adenocarcinoma
Authors: J. Neoptolemos, M. Büchler, D. D. Stocken, P. Ghaneh, D. Smith, C. Bassi, M. Moore, D. Cunningham, C. Dervenis, D. Goldstein
Journal: Journal of Clinical Oncology (2009)

LBA4505 The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology. [Table: see text]