tbuckley/cabot-search huggingface dataset:
The pulmonary physician in critical care * Illustrative case 6: Acute chest syndrome of sickle cell anaemia
Authors: V Mak
Journal: Thorax (2003)

New insights into the pathophysiology of acute chest syndrome (ACS) have highlighted potential therapeutic strategies including the use of nitric oxide. A multidisciplinary approach to the management of patients admitted with a sickle cell crisis is needed to prevent progression to ACS and need for mechanical ventilation.

A 21 year old Afro-Caribbean man with known sickle cell disease (SCD) was admitted to hospital with painful chest, thighs, and generalised abdominal pain. This was his second admission to hospital with a sickle cell crisis. He was on no regular medications apart from analgesia taken at home during crises. Apart from anaemia, there was nothing abnormal to find on examination. The haemoglobin (Hb) was 7.5 g/dl (normal for him), white cell count 22.5 × 109, and the electrolytes were normal apart from a slightly raised C-reactive protein (CRP) level of 30 mg/l. Radiographs of his abdomen and thighs were normal, but his chest radiograph showed a small degree of basal atelectasis bilaterally. His oxygen saturation was 96% on air. He was treated with a subcutaneous opiate infusion using a syringe pump, intravenous fluids, oxygen, and encouraged to drink.

Over the next 24 hours his pain was not well controlled and required an increasing dose of opiates. He became pyrexial (38.5°C), his oxygen saturation fell to 92% on air, and antibiotics to cover community acquired pneumonia were commenced. On the third day, however, he became more drowsy with arterial blood gases of pH 7.35, Pao2 13.5 kPa, and Paco2 7.5 kPa on 40% oxygen. A repeat chest radiograph showed new infiltrates in both lower zones and a diagnosis of acute sickle chest syndrome (ACS) was made. Despite an exchange transfusion, he continued to deteriorate and was eventually intubated and ventilated. On intensive care his Fio2 …
The Flinders Sensitive Line Rat Model of Depression—25 Years and Still Producing
Authors: David H. Overstreet, Gregers Wegener
Journal: Pharmacological Reviews (2013)

Approximately 25 years have passed since the first publication suggesting the Flinders sensitive line (FSL) rat as an animal model of depression. At least 6 years of research on these rats was completed before that seminal paper, and there has been a steady stream of publications (130+) over the years. The present review will focus on several issues not previously covered in earlier reviews, summarize the several lines of ongoing investigations, and propose a novel mechanism that accounts for a number of previously unexplained observations. A key observation in the FSL rat relates to the antidepressant (AD)-like effects of known and putative antidepressants. The FSL rat typically exhibits an AD-like effect in behavioral tests for AD-like activity following chronic (14 days) treatment, although some studies have found AD-like effects after fewer days of treatment. In other observations, exaggerated swim test immobility in the FSL rat has been found to have a maternal influence, as shown by cross-fostering studies and observations of maternal behavior; the implications of this finding are still to be determined. Ongoing or recently completed studies have been performed in the laboratories of Marko Diksic of Canada, Aleksander Mathé of Sweden, Gregers Wegener of Denmark, Brian Harvey of South Africa, Paul Pilowsky and Rod Irvine of Australia, and Gal Yadid of Israel. Jennifer Loftis of Portland, Oregon, and Lynette Daws of San Antonio, Texas, have been working with the FSL rats in the United States. A puzzling feature of the FSL rat is its sensitivity to multiple chemicals, and its greater sensitivity to a variety of drugs with different mechanisms of action. It has been recently shown that each of these drugs feeds through G protein–coupled receptors to potassium-gated channels. Thus, an abnormality in the potassium channel could underlie the depressed-like behavior of the FSL rats.
The Myc–miR-17∼92 Axis Blunts TGFβ Signaling and Production of Multiple TGFβ-Dependent Antiangiogenic Factors
Authors: Michael Dews, Jamie L. Fox, Stacy Hultine, Prema Sundaram, Wenge Wang, Yingqiu Y. Liu, Emma Furth, Gregory H. Enders, Wafik El-Deiry, Janell M. Schelter, Michele A. Cleary, Andrei Thomas-Tikhonenko
Journal: Cancer Research (2010)

c-Myc stimulates angiogenesis in tumors through mechanisms that remain incompletely understood. Recent work indicates that c-Myc upregulates the miR-17∼92 microRNA cluster and downregulates the angiogenesis inhibitor thrombospondin-1, along with other members of the thrombospondin type 1 repeat superfamily. Here, we show that downregulation of the thrombospondin type 1 repeat protein clusterin in cells overexpressing c-Myc and miR-17∼92 promotes angiogenesis and tumor growth. However, clusterin downregulation by miR-17∼92 is indirect. It occurs as a result of reduced transforming growth factor-β (TGFβ) signaling caused by targeting of several regulatory components in this signaling pathway. Specifically, miR-17-5p and miR-20 reduce the expression of the type II TGFβ receptor and miR-18 limits the expression of Smad4. Supporting these results, in human cancer cell lines, levels of the miR-17∼92 primary transcript MIR17HG negatively correlate with those of many TGFβ-induced genes that are not direct targets of miR-17∼92 (e.g., clusterin and angiopoietin-like 4). Furthermore, enforced expression of miR-17∼92 in MIR17HGlow cell lines (e.g., glioblastoma) results in impaired gene activation by TGFβ. Together, our results define a pathway in which c-Myc activation of miR-17∼92 attenuates the TGFβ signaling pathway to shut down clusterin expression, thereby stimulating angiogenesis and tumor cell growth. Cancer Res; 70(20); 8233–46. ©2010 AACR.
The Federation Internationale de Medicine Sportive.
Authors: J. G. Williams
Journal: British Journal of Sports Medicine (1979)

To many people the International Federation of Sports Medicine (FIMS) is something of an unknown quantity, and regrettably too often misrepresented at that.Its value is not always immediately apparent.If one were to sum its purpose and function in a single word, that word would be facilitation, since essentially the FIMS exists to facilitate the development of Sports Medicine throughout the world.
Control of Pain in the Rheumatic Disorders
Authors: F. D. Hart
Journal: BMJ (1968)

Pain may be attacked in the rheumatic diseases (1) centrally, with drugs ranging in efficiency from those which are potentially addictive and under the Dangerous Drugs Act (e.g., pethidine) and are therefore rarely used, down to simple analgesics such as paracetamol; (2) peripherally, by local action, whether it be by applications of heat or cold, by injections of local anaesthetics or anti-inflammatory agents, or by surgery; (3) peripherally, by anti-inflammatory non-analgesic agents taken systemically, such as the corticosteroids; and (4) peripherally, by anti-inflammatory-analgesic-antipyretic agents taken systemically, such as aspirin.The exact sites of action of the pyrazoles, indomethacin, the anthranilic compounds, and other anti-inflammatory-analgesic-antipyretic drugs are as yet uncertain, but along with these methods of attacking the pain-producing areas help must also be given to the distressed mind behind the joints. Faith in the future, cheerfulness, freedom from depression, and the development of a philosophy to deal with the uncertainties of the disease are essential. It has been said that you don't have to be a doctor to treat uncomplicated lobar pneumonia: anybody with a bottle of penicillin in his hands holds the cure. It is the incurable diseases that are really worth treating, and that make demands on the physician. To quote Tuker: "My last word is this. Whoever has the care of a sorely stricken arthritic must encourage him to fulfil himself intellectually and spiritually, and to achieve-no matter what, but to achieve, so that he may nightly lay himself down on his bed of pain looking forward happily to the morrow's task, mind centred upon it, no matter what it is; sticking in stamps, research into anything you like, dabbling with pastel or water colours, writing chatty letters to friends. Anything at all, but let it be for him the most pressing thing of the day, and let him believe that you think it is. Help him and let him live, live fully."This is perhaps the best analgesic of all.
Imatinib mesylate for plexiform neurofibromas in patients with neurofibromatosis type 1: a phase 2 trial
Authors: Kent A Robertson, Grzegorz Nalepa, Feng-Chun Yang, Daniel C Bowers, Chang Y Ho, Gary D Hutchins, James M Croop, Terry A Vik, Scott C Denne, Luis F Parada, Cynthia M Hingtgen, Laurence E Walsh, Menggang Yu, Kamnesh R Pradhan, Mary K Edwards-Brown, Mervyn D Cohen, James W Fletcher, Jeffrey B Travers, Karl W Staser, Melissa W Lee, Marcie R Sherman, Cynthia J Davis, Lucy C Miller, David A Ingram, D Wade Clapp
Journal: The Lancet Oncology (2012)
GLOB-1: a prospective randomised clinical phase III trial comparing vinorelbine–cisplatin with vinorelbine–ifosfamide–cisplatin in metastatic non-small-cell lung cancer patientsAnn Oncol 2002; 13: 1853–1861
Authors: P.J. Souquet, E.H. Tan, J. Rodrigues Pereira, R. Van Klaveren, A. Price, U. Gatzemeier, M. Jaworski, J.P. Burillon, D. Aubert
Journal: Annals of Oncology (2003)

The authors wish to apologise for the omission from the Acknowledgements of the following GLOB-1 investigators: O. Fernandez, Centro Oncologico, Avellaneda, Argentina; C. Lewis, Prince of Wales Hospital, Sydney, Australia; P. De Souza, St George Hospital, Sydney, Australia; L. Bosque, Hôpital de la Citadelle, Liège, Belgium; J. Rodrigues Pereira, Instituto Arnaldo Vieisa de Carvalho, Sao Paulo, Brazil; V. Kolec, University Hospital Olomouc, Czech Republic; M. Marel, University Hospital Motol, Praha, Czech Republic; P. Astoul, Hôpital de la Conception, Marseille, Fance; V. Jounieaux, Hôpital Sud, Amiens, Fance; R. Riou, Centre Hospitalier de Valence, Fance; P.J. Souquet, Centre Hospitalier, Lyon-Sud, France; V. Tack, Centre Hospitalier de Calais, Fance; K.M. Deppermann, Fachkrankenhaus für Lungenheilkunde, Berlin, Germany; U. Gatzemeier, Krankenhaus, Großhansdorf, Germany; G. Koschel, Allgemeines Krankenhaus Harburg, Germany; E.D. Kreuser, Krankenhaus der Barmherzigen Brüder, München, Germany; G. Schlimok, Universitätsklinik, Augsburg, Germany; J. Von Pawel, Zentral Krankenhaus der LVA, Gauting, Germany; O.P. Isokangas, Helsinki University Central Hospital, Finland; K. Mattson, Helsinki University Central Hospital, Finland; L. Torrecillas, Centro Medico Nacional “20 de Noviembre”, Mexico; V. Lira Puerto, Centro Medico Nacional Siglo XXI, Mexico; N. Barroso, Hospital Dr A. Leaño, Zapopan, Mexico; R. Von Klaveren, Klinick Longarts, Rotterdam, The Netherlands; D. Gallardo, Intituto Nacional de Cancerologia, Tlalpan, Mexico; B. Utraka, Centrum Onkologii, Gliwice, Poland; P. Barnardt, Tygerberg Hospital, Capetown, South Africa; E.H. Tan, National Cancer Centre, Singapore; I. Sevilla Garcia, Hospital Virgen de la Victoria, Malaga, Spain; J.A. Moreno Nogueira, Hospital Virgen del Rocío, Sevilla, Spain; D. Betticher, Institute of Medical Oncology, Inselspital, Bern, Switzerland; R. Stahel, Universitatsspital, Zurich, Switzerland; M. Wernli, Kantonsspital, Aarau, Switzerland; J.F. Shih, Veterans General Hospital, Taïwan; P. Clark, Clatterbridge Centre of Oncology, Merseyside, UK; P. Harper, Guy’s Hospital, London, UK; A. Price, Western General Hospital, Edinburgh, UK. GLOB-1: a prospective randomised clinical phase III trial comparing vinorelbine–cisplatin with vinorelbine–ifosfamide–cisplatin in metastatic non-small-cell lung cancer patientsAnnals of OncologyVol. 13Issue 12PreviewThe standard doublet, vinorelbine–cisplatin, was compared with a triplet of vinorelbine–ifosfamide–cisplatin, in terms of survival, in patients with advanced non-small-cell lung cancer (NSCLC). Full-Text PDF Open Archive
Combination antiHER therapeutics — efficacy of alternative dosing regimens in ER+/HER2+ breast cancer xenografts.
Authors: LS Wiechmann, R Soliz, S Hilsenbeck, M Rimawi, CK Osborne, R Schiff
Journal: Cancer Research (2009)

Abstract Abstract #706 Background In preclinical studies of HER2 positive breast cancer, combination antiHER therapy with lapatinib (L) and trastuzumab (T), is more promising than monotherapy. To reduce side effects, cost and increase patient compliance, we investigated novel dosing and scheduling of the L and T combination to find alternative treatment approaches.&amp;#x2028; Methods Mice bearing xenograft tumors of BT474 (ER+/HER2-amplified) cells were treated with control estrogen supplementation, with estrogen withdrawal alone, or with estrogen withdrawal in combination with one or two HER inhibitors (T-10mg/Kg biweekly, L-100mg/Kg 5d/wk) continuously. Alternative dosing regimens included limited treatment duration (14, 42 days), intermittent administration (14 days on/ 14 days off L+T treatment), and dose adjustments (1/2L + 1/2T). Tumor volumes and weights were evaluated weekly. Results were analyzed with the Fisher's exact test or survival analysis methods (Kaplan-Meier estimates) and generalized Wilcoxon test. Group sizes were designed to rule out relatively large decrements in efficacy [i.e. 99% complete regression (CR) vs 65% CR]. All statistical tests were two-sided.&amp;#x2028; Results At day 140 of the experiment, BT474 xenografts demonstrate de novo resistance to estrogen deprivation (ED) and respond more rapidly to the drug combination (L+T) compared to L or T alone. CR rates for xenograft tumors treated for 14 or 42 days are similar to full therapy, although relapses occur earlier (47% relapses at day 140 for 14 day treatment, compared to 20% and 0% for 42 day or full treatment, respectively). Intermittent treatment is as effective as full dose (one mouse demonstrating small palpable growth following CR died before confirmation of relapse). Decreasing the dose did not substantially change the percentage of tumors that undergo complete regression (CR) and did not accelerate treatment failure [Progression Free Survival (PFS) at day 140], but was associated with longer time to complete tumor regression (TTR).&amp;#x2028; &amp;#x2028; Conclusion Intermittent treatment with combined T and L is a promising strategy that warrants further investigation. Though 42 days of therapy led to complete tumor regression, our preliminary data suggest that a sustained response is more likely to be achieved by treatment &amp;gt;42 days. Longer follow up is needed to determine the effectiveness of decreased dose regimens. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 706.
Prolonged survival in patients with persistently elevated tumor markers after chemotherapy for nonseminomatous germ cell cancer
Authors: Z. He, Z. Sun, G. Liu, J. Manola, P. Loehrer
Journal: Journal of Clinical Oncology (2007)

5051 Background: Persistently elevated levels of either AFP or HCG or both after chemotherapy are thought to represent residual viable disease while the normalization of tumor markers predicts favorable outcomes. This study was to evaluate the clinical implication of tumor marker normalization for disseminated nonseminomatous germ cell tumors (GCTs). Methods: This was a retrospective data analysis from two prospective randomized trials (ECOG E4887 and E3887). In E4887, 178 patients with minimal- or moderate-stage disease (Indiana stage) were randomized to receive three cycles of cisplatin plus etoposide with/without bleomycin. In E3887, 304 patients with advanced disseminated GCTs were randomized to receive four cycles of bleomycin, etoposide and cisplatin versus the combination of etoposide, ifosfamide and cisplatin. AFP and HCG were assessed at baseline and after each cycle of chemotherapy. Tumor marker normalization was defined as AFP or HCG normalized after completing chemotherapy. OS and PFS curves were estimated by the Kaplan-Meier method. Multivariate and univariate models, stratified on International Germ Cell Consensus Classification (IGCCCG), were used to assess the impact of marker normalization for patients with abnormal markers at study entry. Results: Median follow-up is 14.8 years. About 40% to 60% of Patients with persistently elevated AFP or HCG after chemotherapy have prolonged PFS and/or OS. In IGCCCG poor risk patients, 35% to 55% of them with persistently elevated AFP or HCG after chemotherapy have prolonged PFS and/or OS. There is a statistically significant difference in OS associated with AFP normalization in both multivariate (p=0.008, HR=0.51 with 95% CI=0.31–0.84) and univariate analysis (p=0.0008, HR=0.43 with 95% CI=0.26–0.71). However, there was no statistically significant difference in OS associated with normalization of HCG in both multivariate analysis (p=0.52, HR=0.84 with 95% CI=0.50–1.41) and univariate analysis (p=0.29, HR=0.76 with 95% CI=0.46–1.26). Conclusions: Patients with persistently elevated AFP or HCG after chemotherapy may still have prolonged PFS and/or OS. Normalization of AFP but not HCG is associated with better OS in patients with disseminated nonseminomatous GCTs. No significant financial relationships to disclose.
Retinal Thinning as a Marker of Disease Progression in Patients With Wolfram Syndrome
Authors: Agnieszka Zmyslowska, Wojciech Fendler, Anna Niwald, Malgorzata Ludwikowska-Pawlowska, Maciej Borowiec, Karolina Antosik, Agnieszka Szadkowska, Wojciech Mlynarski
Journal: Diabetes Care (2015)

Wolfram syndrome (WFS), caused by recessive mutations in WFS1 , is characterized by neurodegeneration due to apoptosis provoked by increased endothelial reticulum stress (1). Currently, it is incurable and leads to a premature death at an average age of 35 years (2). Despite initial success with spectroscopy-based studies (3), there is a lack of repeatable and robust markers for monitoring the clinical course of WFS. The aim of our study was to evaluate retinal parameters, measured with optical coherence tomography, as biomarkers of WFS progression. The Ethics Committee of the Medical University of Lodz approved the project (RNN/140/13/KE). Optical coherence tomography was performed after mydriasis using the Topcon 3D OCT-2000 system. Average retinal thickness and central thickness were measured using three-dimensional disc and macula scans covering a retinal area of 6 × 6 mm. The study was performed between August 2013 and April 2014. Two cohorts were enrolled: a pediatric/adolescent group and an adult one. The first consisted of patients with genetically confirmed WFS (median age 17.25 [interquartile range …
Physicians’ Experiences With <i>BRCA1/2</i> Testing in Community Settings
Authors: Nancy L. Keating, Kathryn A. Stoeckert, Meredith M. Regan, Lisa DiGianni, Judy E. Garber
Journal: Journal of Clinical Oncology (2008)

Purpose We surveyed a national sample of nonacademic physicians who ordered BRCA1/2 testing to understand their implementation of genetic testing and to assess recommendations for surveillance and cancer risk management of women with positive test results. Patients and Methods We surveyed physicians (N = 611 of 1,050; response rate, 58.2%) practicing in nonacademic settings who ordered BRCA1/2 testing during 2004 to 2005. We described physicians’ experiences with testing and used multivariable regression models to identify factors associated with more complete counseling and with recommendations for cancer risk management for a BRCA1 mutation carrier. Results Most physicians (68.2%) usually or always discussed six counseling items before testing. In adjusted analyses, physicians who were assisted by genetic counselors, nurse geneticists, or others (v counseling by themselves), those who spent more than 60 minutes in counseling, and medical oncologists (v surgeons or geneticists) were more likely to discuss all six items (all P &lt; .05). A total of 61.4% of physicians would recommend bilateral prophylactic mastectomy to a 38-year-old BRCA1 mutation carrier who had completed childbearing. After adjustment, geneticists and gynecologists were less likely than medical oncologists and surgeons to recommend prophylactic mastectomy (P &lt; .001), as were physicians in the Northeast versus those in other regions of the United States (P = .01). Conclusion Community-based physicians seem to be successfully incorporating BRCA1/2 testing into their practices. Physicians’ recommendations for surveillance of mutation carriers are generally consistent with practice guidelines, yet recommendations for preference-based procedures such as prophylactic mastectomy vary by physician characteristics such as specialty and geographic region. The providers whom patients see for testing may contribute to variations in prophylactic treatments.
PTU-103 Anti-infliximab antibodies: prevalence, infusion reactions, immunosuppression and response, a meta-analysis: Abstract PTU-103 Table 1
Authors: L Y Lee, J Sanderson, P Irving
Journal: Gut (2012)

<h3>Introduction</h3> Infliximab is a chimeric monoclonal antibody directed against tumour necrosis factor α. When used in inflammatory bowel disease (IBD), primary non-response is seen in at least 10% of patients with secondary loss of response occurring in a further 10%–15% per year. It has been suggested that this may in part be a result of the development of anti-infliximab antibodies (ATIs). The prevalence of ATIs varies according to the frequency of administration of infliximab and the use of immunosuppressants. ATIs have also been linked with infusion and hypersensitivity reactions. We aimed to perform a meta-analysis of the prevalence of ATIs in people with IBD receiving infliximab, the effect of immunosuppressive drugs on prevalence of ATIs and the effects of ATIs on infusion reactions and remission rates. <h3>Methods</h3> MEDLINE and EMBASE databases were systematically searched from 1948 and 1980 respectively to October 2011. Inclusion criteria included randomised controlled trials, cohort studies or case series reporting on anti-infliximab antibodies in adult or juvenile IBD. Data from eligible studies were extracted into a standardised form and a meta-analysis performed. <h3>Results</h3> 18 studies involving 3326 patients were included. The prevalence of ATIs was 45.8% when episodic infusions of infliximab were given and 12.4% when maintenance infliximab was given. Rates of infusion reactions were significantly higher in patients with ATIs (RR: 2.07, 95% CI 1.61 to 2.67). Immunosuppressants resulted in a 50% risk reduction in prevalence of ATIs. The prevalence of ATIs was 17.5% in patients using immunosuppressants and 37.7% in those who were not (RR: 0.50, 95% CI 0.42 to 0.59). However, the presence or absence of ATIs did not significantly affect rates of clinical remission, which was 46.5% in patients with ATIs and 60.2% in those without (p=0.10). <h3>Conclusion</h3> The prevalence of ATIs depends on the regimen of infliximab administration and the use of immunosuppressants. Patients who develop ATIs are at increased risk of infusion reactions, but the presence of ATIs does not, by itself, have an effect on rates of clinical remission. <h3>Competing interests</h3> None declared.