tbuckley/cabot-search huggingface dataset:
Combination of HSP90 inhibitor onalespib with crizotinib to treat or delay resistance in NSCLC: Preclinical and Clinical Investigations
Authors: H. Keer, T. Smyth, A. Courtin, K. Hearn, J. Lyons, N. Wallis, A. Oganesian, M. Azab
Journal: Annals of Oncology (2015)
Gut Microbiota Metabolism of Anthocyanin Promotes Reverse Cholesterol Transport in Mice Via Repressing miRNA-10b
Authors: Dongliang Wang, Min Xia, Xiao Yan, Dan Li, Lei Wang, Yuxuan Xu, Tianru Jin, Wenhua Ling
Journal: Circulation Research (2012)

Rationale: We and others have demonstrated that anthocyanins have antiatherogenic capability. Because intact anthocyanins are absorbed very poorly, the low level of circulating parent anthocyanins may not fully account for their beneficial effect. We found recently that protocatechuic acid (PCA), a metabolite of cyanidin-3 to 0-β-glucoside (Cy-3-G), has a remarkable antiatherogenic effect. Objective: To investigate whether mouse gut microbiota metabolizes Cy-3-G into PCA and to determine whether and how PCA contributes to the antiatherogenic potency of its precursor, Cy-3-G. Methods and Results: PCA was determined as a gut microbiota metabolite of Cy-3-G in ApoE −/− mice, verified by the utilization of antibiotics to eliminate gut microbiota and further microbiota acquisition. PCA but not Cy-3-G at physiologically reachable concentrations promoted cholesterol efflux from macrophages and macrophage ABCA1 and ABCG1 expression. By conducting a miRNA microarray screening, we revealed that expression of miRNA-10b in macrophages can be reduced by PCA. Functional analyses demonstrated that miRNA-10b directly represses ABCA1 and ABCG1 and negatively regulates cholesterol efflux from murine- and human-derived macrophages. Further in vitro and ex vivo analyses verified that PCA accelerates macrophage cholesterol efflux, correlating with the regulation of miRNA-10b-ABCA1/ABCG1 cascade, whereas Cy-3-G consumption promoted macrophage RCT and regressed atherosclerotic lesion in a gut microbiotaendependent manner. Conclusions: PCA, as the gut microbiota metabolite of Cy-3-G, exerts the antiatherogenic effect partially through this newly defined miRNA-10b-ABCA1/ABCG1-cholesterol efflux signaling cascade. Thus, gut microbiota is a potential novel target for atherosclerosis prevention and treatment.
An activating ALK gene mutation in ALK IHC-positive/FISH-negative nonsmall-cell lung cancer
Authors: Y. Togashi, H. Mizuuchi, Y. Kobayashi, H. Hayashi, M. Terashima, K. Sakai, E. Banno, T. Mizukami, Y. Nakamura, M.A. de Velasco, Y. Fujita, S. Tomida, T. Mitsudomi, K. Nishio
Journal: Annals of Oncology (2015)
Penfluridol: An Efficacious Long-Acting Oral Antipsychotic Compound
Authors: DONALD M. GALLANT, DAVID H. MIELKE, MORRIS A. SPIRTES, WILLIAM C. SWANSON, ROBERT BOST
Journal: American Journal of Psychiatry (1974)

A six-month evaluation of penfluridol, a long-acting oral preparation, was conducted with 50 severely ill schizophrenic patients. After an initial three-month stabiization period, the patients were divided into two equal groups and a double-blind evaluation of penfluridol versus placebo was conducted. The results of this study indicate that weekly administration of penfluridol (one oral dose) provides relatively safe and adequate control of severely ill schizophrenic patients and displays efficacy similar to that of the shorter-acting antipsychotic agents. If these results are confirmed by other clinical investigators, this medication may prove to be of invaluable help in maintaining the schizophrenic patient in his community.
In vitro and in vivo effects of salbutamol on neutrophil function in acute lung injury
Authors: G D Perkins, N Nathani, D F McAuley, F Gao, D R Thickett
Journal: Thorax (2006)

<b>Background:</b> Intravenous salbutamol (albuterol) reduces lung water in patients with the acute respiratory distress syndrome (ARDS). Experimental data show that it also reduces pulmonary neutrophil accumulation or activation and inflammation in ARDS. <b>Aim:</b> To investigate the effects of salbutamol on neutrophil function. <b>Methods:</b> The in vitro effects of salbutamol on neutrophil function were determined. Blood and bronchoalveolar lavage (BAL) fluid were collected from 35 patients with acute lung injury (ALI)/ARDS, 14 patients at risk from ARDS and 7 ventilated controls at baseline and after 4 days' treatment with placebo or salbutamol (ALI/ARDS group). Alveolar–capillary permeability was measured in vivo by thermodilution (PiCCO). Neutrophil activation, adhesion molecule expression and inflammatory cytokines were measured. <b>Results:</b> In vitro, physiological concentrations of salbutamol had no effect on neutrophil chemotaxis, viability or apoptosis. Patients with ALI/ARDS showed increased neutrophil activation and adhesion molecule expression compared with at risk-patients and ventilated controls. There were associations between alveolar–capillary permeability and BAL myeloperoxidase (r = 0.4, p = 0.038) and BAL interleukin 8 (r = 0.38, p = 0.033). In patients with ALI/ARDS, salbutamol increased numbers of circulating neutrophils but had no effect on alveolar neutrophils. <b>Conclusion:</b> At the onset of ALI/ARDS, there is increased neutrophil recruitment and activation. Physiological concentrations of salbutamol did not alter neutrophil chemotaxis, viability or apoptosis in vitro. In vivo, salbutamol increased circulating neutrophils, but had no effect on alveolar neutrophils or on neutrophil activation. These data suggest that the beneficial effects of salbutamol in reducing lung water are unrelated to modulation of neutrophil-dependent inflammatory pathways.
Travel by air for patients with COPD
Authors: R K SINHA;, M G PEARSON, P M A CALVERLEY
Journal: Thorax (1998)

Publication of the long awaited BTS guidelines on the management of COPD has been welcomed by all concerned and will go a long way towards providing a practical guidance on management of patients with COPD.

However, I would like to comment on the section on travel (page S14).This informs us that aircraft are pressurised to the equivalent of 900–2400 metres above sea level and that a Pao 2 of less than 6.7 kPa should be considered as a relative contraindication to air travel.

A Pao2  of 6.7 kPa at sea level will equate to a Pa …
Measured GFR as a Confirmatory Test for Estimated GFR
Authors: Lesley A. Stevens, Andrew S. Levey
Journal: Journal of the American Society of Nephrology (2009)

Clinical assessment of kidney function is central to the practice of medicine. GFR is widely accepted as the best index of kidney function in health and disease, and accurate values are required for optimal decision making. Estimated GFR based on serum creatinine is now widely reported by clinical laboratories, and in most circumstances, estimated GFR is sufficient for clinical decision making. GFR estimates may be inaccurate in the non–steady state and in people in whom non-GFR determinants differ greatly from those in whom the estimating equation was developed. If GFR estimates are likely inaccurate or if decisions based on inaccurate estimates may have adverse consequences, a measured GFR is an important confirmatory test. Endogenous creatinine clearance is the most common method used to measure GFR in clinical practice but may be difficult to obtain or fraught with error. We review methods for GFR measurement using urinary and plasma clearance of exogenous filtration markers and focus on urinary clearance of iothalamate and plasma clearance of iohexol compared with inulin clearance. We suggest plasma clearance of nonradioactive markers be more widely implemented in clinical settings. Further research is necessary on the impact of the use of measured GFR as a confirmatory test.
Phase II clinical trial of neoadjuvant trabectedin in patients with advanced localized myxoid liposarcoma
Authors: A. Gronchi, B.N. Bui, S. Bonvalot, S. Pilotti, S. Ferrari, P. Hohenberger, R.J. Hohl, G.D. Demetri, A. Le Cesne, P. Lardelli, I. Pérez, A. Nieto, J.C. Tercero, V. Alfaro, E. Tamborini, J.Y. Blay
Journal: Annals of Oncology (2011)

BackgroundTo evaluate neoadjuvant trabectedin (1.5 mg/m2 24-h i.v. infusion every 3 weeks; three to six cycles) in patients with locally advanced myoxid liposarcoma (ML) previously untreated with chemotherapy or radiation.Patients and methodsPrimary efficacy end point was pathological complete response (pCR) or tumoral regression rate. Objective response according to RECIST (v.1.0) was a secondary end point.ResultsThree of 23 assessable patients had pCR [13%; 95% confidence interval (CI), 3% to 34%]. Furthermore, very good and moderate histological responses were observed in another 2 and 10 patients, respectively. Histological decrement in the cellular and vascular tumor component and maturation of tumor cells to lipoblasts were observed in both myoxid and myoxid/round cell variants. Seven patients had partial response according to RECIST (objective response rate of 24%; 95% CI, 10% to 44%). No disease progression was reported. Neoadjuvant trabectedin was usually well tolerated, with a safety profile similar to that described in patients with soft tissue sarcoma or other tumor types.ConclusionTrabectedin 1.5 mg/m2 given as a 24-h i.v. infusion every 3 weeks is a therapeutic option in the neoadjuvant setting of ML.
Effect of colchicine on intestinal disaccharidases: correlation with biochemical aspects of cellular renewal
Authors: John J. Herbst, Ruth Hurwitz, Philip Sunshine, Norman Kretchmer
Journal: Journal of Clinical Investigation (1970)

There was a significant depression of the activities of intestinal lactase, invertase, and alkaline phosphatase in rats given drinking water containing 2.5 mg of colchicine per 100 ml. Activities of intestinal maltase, aspartate transcarbamylase, and dihydroorotase were not affected by the drug. Injection of colchicine (1 mg/kg) caused depression of intestinal invertase activity within 8 hr. Investigation of the effect of colchicine on the disaccharides in vitro demonstrated that invertase and maltase were not affected by concentrations up to 125 mg/100 ml. Intestinal lactase was inhibited by concentrations exceeding 5 mg/100 ml. Calculation of the concentration of colchicine present in the intestine, after a single injection, indicated that the in vivo effect of colchicine was not due to simple enzyme inhibition. Histological examination showed an increase in crypt cells but no decrease in the length of the villi. Cellular migration along the villi, as well as activity of uridine kinase in intestinal mucosa, was increased in colchicine-treated rats. It was concluded that colchicine did not depress intestinal invertase, lactase, and alkaline phosphatase by decreasing cellular renewal, but rather it exerted its effect directly on the differentiated cells of the villus.
BTS guidelines for home oxygen in children
Authors: I M Balfour-Lynn, D J Field, P Gringras, B Hicks, E Jardine, R C Jones, A G Magee, R A Primhak, M P Samuels, N J Shaw, S Stevens, C Sullivan, J A Taylor, C Wallis
Journal: Thorax (2009)

… as we know, there are known knowns; there are things we know we know.We also know there are known unknowns; that is to say we know there are some things we do not know.But there are also unknown unknowns -the ones we don't know we don't know.
A Short-Term Trial of Tacrolimus Ointment for Atopic Dermatitis
Authors: Thomas Ruzicka, Thomas Bieber, Erwin Schöpf, Andris Rubins, Attila Dobozy, Jan D. Bos, Stefania Jablonska, Imitiaz Ahmed, Kristian Thestrup-Pedersen, Francois Daniel, Aldo Finzi, Sakari Reitamo
Journal: New England Journal of Medicine (1997)

Tacrolimus (FK 506) is an effective immunosuppressant drug for the prevention of rejection after organ transplantation, and preliminary studies suggest that topical application of tacrolimus is effective in the treatment of atopic dermatitis.
External Incentives, Information Technology, and Organized Processes to Improve Health Care Quality for Patients With Chronic Diseases
Authors: Lawrence Casalino, Robin R. Gillies, Stephen M. Shortell, Julie A. Schmittdiel, Thomas Bodenheimer, James C. Robinson, Thomas Rundall, Nancy Oswald, Helen Schauffler, Margaret C. Wang
Journal: JAMA (2003)

<h3>Context</h3> Organized care management processes (CMPs) can improve health care quality for patients with chronic diseases. The Institute of Medicine of the National Academy of Sciences has called for public and private purchasers of health care to create incentives for physician organizations (POs) to use CMPs and for the government to assist POs in implementing information technology (IT) to facilitate CMP use. Research is lacking about the extent to which POs use CMPs or about the degree to which incentives, IT, or other factors are associated with their use. <h3>Objectives</h3> To determine the extent to which POs with 20 or more physicians use CMPs and to identify key factors associated with CMP use for 4 chronic diseases (asthma, congestive heart failure, depression, and diabetes). <h3>Design, Setting, and Participants</h3> One thousand five hundred eighty-seven US POs (medical groups and independent practice associations) with 20 or more physicians were identified using 5 large databases. One thousand one hundred four of these POs (70%) agreed to participate in a telephone survey conducted between September 2000 and September 2001. Sixty-four responding POs were excluded because they did not treat any of the 4 diseases, leaving 1040 POs. <h3>Main Outcome Measures</h3> Extent of use of CMPs as calculated on the basis of a summary measure, a PO care management index (POCMI; range, 0-6) and factors associated with CMP use. <h3>Results</h3> Physician organizations' mean use of CMPs was 5.1 of a possible 16; 50% used 4 or fewer. External incentives and clinical IT were most strongly associated with CMP use. Controlling for other factors, use of the 2 most strongly associated incentives—public recognition and better contracts for health care quality—was associated with use of 1.3 and 0.7 additional CMPs, respectively (<i>P</i>&lt;.001 and<i>P</i>= .007). Each additional IT capability was associated with 0.37 additional CMPs (<i>P</i>&lt;.001). However, 33% of POs reported no external incentives and 50% reported no clinical IT capability. <h3>Conclusions</h3> The use of CMPs varies greatly among POs, but it is low on average. Government and private purchasers of health care may increase CMP use by providing external incentives for improvement of health care quality to POs and by assisting them in improving their clinical IT capability.
Sexual and physical abuse are not associated with rectal hypersensitivity in patients with irritable bowel syndrome
Authors: Y Ringel
Journal: Gut (2004)

<b>Background:</b> Patients with irritable bowel syndrome (IBS) have reduced pain thresholds for rectal distension. In addition, the prevalence of sexual/physical abuse in referred IBS patients is high and is associated with greater pain reporting, poorer health status, and poorer outcome. This lead to a hypothesis that abuse history may sensitise patients to report pain at a lower threshold. <b>Aim:</b> To compare rectal pain thresholds in women with IBS who had a history of severe abuse to IBS women with no history of abuse. <b>Methods:</b> We studied 74 IBS patients with a history of severe physical and/or sexual abuse and 85 patients with no history of abuse. Abuse history was assessed by a previously validated self-report abuse screening questionnaire. Rectal sensory thresholds were assessed using an electronic barostat and determined by the ascending method of limit (AML) and by the tracking technique. <b>Results:</b> IBS patients with a history of severe abuse had significantly higher rectal pain thresholds, as measured by AML (F (1, 111) = 6.06; p = 0.015) and the tracking technique (F (1, 109) = 5.21; p = 0.024). Patients with a history of severe abuse also reported a significantly higher threshold for urgency to defecate (F (1, 113) = 11.23; p = .001). <b>Conclusion:</b> Severe sexual/physical abuse is associated with higher urge and pain thresholds for rectal distension in IBS patients. This suggests that the greater pain reporting and poorer health status in IBS patients with abuse history are not related to increased rectal pain sensitivity. Further studies are needed to determine the causes of these findings.
Rupture of aortic aneurysm with right-sided haemothorax
Authors: F Baharloo, R Verhelst, P Collard, T Pieters
Journal: European Respiratory Journal (1999)

A 62-yr-old male with a history of high blood pressure was admitted for persistent dyspnoea and a right-sided pleural effusion, complicated by a recent episode of shock. There was no history of trauma and the patient denied any thoracic pain. A chest tube was inserted which released nonclotting bloody fluid. A thoracic computed tomographic scan of the chest revealed an aneurysm of the inferior third of the descending thoracic aorta. The patient underwent a successful prosthetic graft replacement. We emphasize that rupture of aortic aneurysms should be considered in the evaluation of spontaneous haemothorax even if it is right-sided and not associated with pain.
Histone deacetylase inhibition rescues structural and functional brain deficits in a mouse model of Kabuki syndrome
Authors: Hans T. Bjornsson, Joel S. Benjamin, Li Zhang, Jacqueline Weissman, Elizabeth E. Gerber, Yi-Chun Chen, Rebecca G. Vaurio, Michelle C. Potter, Kasper D. Hansen, Harry C. Dietz
Journal: Science Translational Medicine (2014)

A neurogenesis defect in a mouse model of Kabuki syndrome can be ameliorated postnatally using histone deacetylase inhibitors.
Contraceptive services for ethnic minorities.
Authors: J Fuller
Journal: BMJ (1987)

Much family planning advice for members of ethnic minorities in Britain is provided by physicians from a different culture--the ethnic majority.  It is essential that family planning programs are familiar with the special needs of the communities they service and the cultural factors that influence decisions on contraceptives.  Publicity about services should be in a form accessible to all communities.  Authorities should further consider who provides family planning services.  The goal should be to offer wide choices of advisers in terms of sex race and class.  In addition however staff should be given training in areas such as racism awareness cross-cultural counseling and health and religious beliefs in minority communities.  Areas with large communities of ethnic minorities should consider employing patient advocates--trained members of ethnic minorities who both interpret the patients needs and beliefs and interpret the needs of the medical community to the patients.  Any improvements in contraceptive services for ethnic minorities will have the additional effect of improving services for the majority.  Finally decisions on contraceptive services for minorities should be based on information from workers who originate from the ethnic communities.
Value of bronchoalveolar lavage in the management of severe acute pneumonia and interstitial pneumonitis in the immunocompromised child.
Authors: J de Blic, P McKelvie, M Le Bourgeois, S Blanche, M R Benoist, P Scheinmann
Journal: Thorax (1987)

The diagnostic value of 73 bronchoalveolar lavages was assessed in 67 immunocompromised children (aged 3 months to 16 years) with pulmonary infiltrates. Thirty one children had primary and 19 secondary immune deficiency, 14 acquired immunodeficiency syndrome (AIDS), and three AIDS related complex. Bronchoalveolar lavage was performed during fibreoptic bronchoscopy, under local anaesthesia in all but two. One or more infective agents was found in eight of 11 patients with severe acute pneumonia and in 26 of 62 patients with interstitial pneumonitis. In interstitial pneumonitis, the most frequently encountered agents were Pneumocystis carinii (12), cytomegalovirus (8), and Aspergillus fumigatus (3). The yield was related to the severity of interstitial pneumonitis. The mean cellular count and cytological profile in lavage returns from patients with varying infective agents or underlying pathological conditions showed no significant difference, except in those children with AIDS and AIDS related complex who had appreciable lymphocytosis (mean percentage of lymphocytes 28 (SD 17]. In children with AIDS and chronic interstitial pneumonitis lymphocytosis without pneumocystis infection was observed in eight of nine bronchoalveolar lavage returns and was suggestive of pulmonary lymphoid hyperplasia. Finally, bronchoalveolar lavage produced a specific diagnosis from the microbiological or cytological findings in 44 instances (60%). Transient exacerbation of tachypnoea was observed in the most severely ill children but there was no case of respiratory decompensation attributable to the bronchoscopy. Bronchoalveolar lavage is a safe and rapid examination for the investigation of pulmonary infiltrates in immunocompromised children. It should be performed as a first line investigation and should reduce the use of open lung biopsy techniques.
An assessment of disease flare in patients with systemic lupus erythematosus: a comparison of BILAG 2004 and the flare version of SELENA
Authors: D. A. Isenberg, E. Allen, V. Farewell, D. D'Cruz, G. S. Alarcon, C. Aranow, I. N. Bruce, M. A. Dooley, P. R. Fortin, E. M. Ginzler, D. D. Gladman, J. G. Hanly, M. Inanc, K. Kalunian, M. Khamashta, J. T. Merrill, O. Nived, M. Petri, R. Ramsey-Goldman, G. Sturfelt, M. Urowitz, D. J. Wallace, C. Gordon, A. Rahman
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Aims</h3> To compare the British Isles Lupus Assessment Group (BILAG) 2004, the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) flare index (SFI) and physician9s global assessment (PGA) in assessing flares of disease activity in patients with systemic lupus erythematosus (SLE). <h3>Methods</h3> Sixteen patients with active SLE were assessed by a panel of 16 rheumatologists. The order in which the patients were seen was randomised using a 4×4 Latin square design. Each patient9s flare status was determined at each assessment using the BILAG 2004 activity index; the SFI and a PGA. A group of five specialists designated each patient into severe, moderate, mild or no flare categories. <h3>Results</h3> The rate of complete agreement (95% CI) of the four individual examining physicians for any flare versus no flare was 81% (55% to 94%), 75% (49% to 90%) and 75% (49% to 90%) for the BILAG 2004 index, SELENA flare instrument and PGA, respectively. The overall agreement between flare defined by BILAG 2004 and the SFI was 81% and when type of flare was considered was 52%. Intraclass correlation coefficients (95% CI), as a measure of internal reliability, were 0.54 (0.32 to 0.78) for BILAG 2004 flare compared with 0.21 (0.08 to 0.48) for SELENA flare and 0.18 (0.06 to 0.45) for PGA. Severe flare was associated with good agreement between the indices but mild/moderate flare was much less consistent. <h3>Conclusions</h3> The assessment of flare in patients with SLE is challenging. No flare and severe flare are identifiable but further work is needed to optimise the accurate 'capture' of mild and moderate flares.