tbuckley/cabot-search huggingface dataset:
Spirometry in primary care
Authors: P. T WHITE
Journal: Thorax (2000)

<h3>Background</h3> There are many barriers to advance care planning in paediatrics. High expectations for cure, difficulties prognosticating and a lack of training in how to approach thèse conversations mean that care planning often occurs late or not at all. Further, many of the advance care planning documents developed to date focus on interventions rather than goals of care. This can drive ‘tick box’ discussions which both paediatricians and parents find confronting. <h3>Aim</h3> To create a suite of resources to assist paediatricians and families to engage in discussions regarding goals of care as a means of facilitating advance care planning. <h3>Methods</h3> Literature review, consultation with paediatricians and families, and an audit of patient deaths to identify potential triggers for advance care planning. <h3>Results</h3> Development of; A Goals of Patient Care Document consisting of six components, all accessible via an electronic medical record and able to capture evolving discussions and decisions, A discussion guide for paediatricians outlining key principles and suggested phrases, An on-line education module for health professionals, A set of triggers for advance care planning, A written resource for parents. <h3>Discussion/conclusion</h3> Advance care planning requires the development of tools to capture both decisions made and discussions in progress. Paediatricians need assistance to identify when advance care planning is needed and suggested ways of approaching the discussion. Audit and research is now required to determine the efficacy of this newly developed suite of resources.
Book Review Chronic Pelvic Pain: Evaluation and management Edited by Richard E. Blackwell and David L. Olive. 235 pp., illustrated. New York, Springer–Verlag, 1998. $59. 0-387-98207-8 Chronic Pelvic Pain: An integrated approach Edited by John F. Steege, Deborah A. Metzger, and Barbara S. Levy. 365 pp., illustrated. Philadelphia, W.B. Saunders, 1998. $60. 0-7216-6529-2
Authors: G. David Adamson
Journal: New England Journal of Medicine (1998)
Different effect of hormone replacement therapy, DHEAS, and tibolone on endothelial function in postmenopausal women with increased cardiovascular risk
Authors: Cristiana Vitale, Otavio Gebara, Massimo Fini, Mauricio Wajngarten, JosèMendes Aldrighi, Antonello Silvestri, Paola Rossini, Sandra Zoncu, Cristiano Sarais, JosèAntonio Ramires, Giuseppe Mercuro, Giuseppe M. Rosano
Journal: Journal of the American College of Cardiology (2002)
Characterizing Young Patients With Diabetes and Non–ST-Segment Elevation Acute Coronary Syndromes
Authors: Rajendra H. Mehta, Sarah Milford-Beland, Eric D. Peterson, Deepak L. Bhatt, Michael E. Farkouh, Gerald X. Brogan, W. Brian Gibler, E. Magnus Ohman, Matthew T. Roe
Journal: Diabetes Care (2007)

Most information regarding the prognosis and quality of care of patients with diabetes and acute coronary syndromes (ACSs) is derived from studies that have largely focused on middle-aged and older populations (1–3). Thus, data regarding the presenting features, treatment patterns, and outcomes in smaller proportions of ACS patients with diabetes who are young (an age wherein insulin-dependent diabetes manifests, often portending poor prognosis) has been less well characterized. Accordingly, we sought to evaluate clinical features, management, and in-hospital clinical events among young patients (aged ≤45 years) with and without diabetes who presented with non–ST-segment elevation ACS (NSTE ACS) and who were included in the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines?) Quality Improvement Initiative (4–6).

The details of the CRUSADE Initiative have been previously published (4–6). In brief, patients included in the CRUSADE Quality Improvement Initiative were admitted to 498 participating U.S. hospitals with ischemic symptoms at rest within 24 h before presentation and high-risk features including ST-segment depression, transient ST-segment elevation, and/or positive cardiac markers (elevated troponin I or T and/or creatine kinase-MB more than the upper limit of normal for participating institutions). For this study, we analyzed data from 9,643 patients aged ≤45 years out of …
Sensitive Subgroups and Normal Variation in Pulmonary Function Response to Air Pollution Episodes
Authors: Bert Brunekreef, Patrick L. Kinney, James H. Ware, Douglas Dockery, Frank E. Speizer, John D. Spengler, Benjamin G. Ferris
Journal: Environmental Health Perspectives (1991)

The Clean Air Act requires that sensitive subgroups ofexposed populations be protected from adverse health effects of air poUlution exposure.Hence, data suggesting the existence of sensitive subgroups can have an important inpact on regulatory decisions.Some investigators have interpreted differences among individuals in observed pulmonary func- tion response to air pollution episodes as evidence that individuals differ in their sensitivity.An alternative explanation is that the differences are due entirely to normal variation in repeated pulmonary function measurements.This paper investigates this question by reanalyzing data from three studies ofchildren exped to air pollution episodes to determine whether the observed variability in pulmonary function response indicates differences in sensitivity or natural interoc- casion variability .One study investigated exposures to total suspended particulates (ISP), the other two investigated ex- posure to ozone.In all studies, each child's response to air pollution exposures was mari by regressing that child's set of pulnonary function measurements on the air pollution concentrations on the day or daysbefore messurement.The within-child and between-child variances of these slopes were used to test the bypothesis ofvariable sensitivit.Regression slopes did not vary sintlyamongchildren exposedtoepisodesofhigh liSPconcentrtion, buttherewasevidence of heterogeneity in both studies of ozone exposures.The fmding of heterogeneous response to ozone exposure is consis- tent with the epidemiologic and chamber studies ofozone exposures, but the lack ofevidence for heterogeneous response to TSP exposures implies that observed variation in response can be explained by sampling variability rather than the presence of sensitive subgroup.
Specific recommendations for PROs and HRQoL assessment in allergic rhinitis and/or asthma: a GA<sup>2</sup>LEN taskforce position paper
Authors: F. Braido, P. J. Bousquet, Z. Brzoza, G. W. Canonica, E. Compalati, A. Fiocchi, W. Fokkens, R. Gerth van Wijk, S. La Grutta, C. Lombardi, M. Maurer, A. M. Pinto, E. Ridolo, G. E. Senna, I. Terreehorst, A. Todo Bom, J. Bousquet, T. Zuberbier, I. Baiardini
Journal: Allergy (2010)

The GA(2)LEN taskforce on Patient-Reported Outcomes (PROs) and Health-Related Quality of Life (HRQoL) published in 2009 a position paper concerning PROS and HRQoL assessment in clinical trials on allergy. Because of the specificity of this topic in asthma and rhinitis, specific recommendations are needed. The aim of this position paper is to define PROs and their meaning in asthma and rhinitis research, explore the available tools to provide criteria for a proper choice, identify patient-related factor which could influence PROs assessment, define specific recommendations for assessment, analysis and results spreading, underline the unexplored areas and unmet needs. PROs assessment is gaining increasing importance, and it must be performed with a rigorous methodological procedure and using validated tools. This approach enables to better understand patient-related factors influencing clinical trials and real-life management outcomes, identify patients subgroups that can benefit from specific treatment and management plan and tailor treatment to address PROs (not only physician-defined targets) to improve asthma and rhinitis management.
Adult respiratory distress syndrome (ARDS) due to bacteraemic pneumococcal pneumonia
Authors: GP Mannes, WG Boersma, CH Baur, PE Postmus
Journal: European Respiratory Journal (1991)

We describe a patient, who had no pre-existing disease, with bacteraemic pneumococcal pneumonia and adult respiratory distress syndrome (ARDS), a rare complication. In spite of the use of antibiotics and intensive treatment the mortality rate of this kind of infection remains high. Streptococcus pneumoniae is the most frequently found micro-organism responsible for community-acquired pneumonia. In 25-35% of these patients pneumococcal bacteraemia is found, with a 2-3 times higher mortality rate than that for non-bacteraemic pneumococcal pneumonia.
MHC Class I Antigen Processing and Presenting Machinery: Organization, Function, and Defects in Tumor Cells
Authors: P. Leone, E.-C. Shin, F. Perosa, A. Vacca, F. Dammacco, V. Racanelli
Journal: JNCI Journal of the National Cancer Institute (2013)

The surface presentation of peptides by major histocompatibility complex (MHC) class I molecules is critical to all CD8 + T-cell adaptive immune responses, including those against tumors. The generation of peptides and their loading on MHC class I molecules is a multistep process involving multiple molecular species that constitute the so-called antigen processing and presenting machinery (APM). The majority of class I peptides begin as proteasome degradation products of cytosolic proteins. Once transported into the endoplasmic reticulum by TAP (transporter associated with antigen processing), peptides are not bound randomly by class I molecules but are chosen by length and sequence, with peptidases editing the raw peptide pool. Aberrations in APM genes and proteins have frequently been observed in human tumors and found to correlate with relevant clinical variables, including tumor grade, tumor stage, disease recurrence, and survival. These findings support the idea that APM defects are immune escape mechanisms that disrupt the tumor cells’ ability to be recognized and killed by tumor antigen–specific cytotoxic CD8 + T cells. Detailed knowledge of APM is crucial for the optimization of T cell–based immunotherapy protocols.
Genomic Heterogeneity of Translocation Renal Cell Carcinoma
Authors: Gabriel G. Malouf, Federico A. Monzon, Jérôme Couturier, Vincent Molinié, Bernard Escudier, Philippe Camparo, Xiaoping Su, Hui Yao, Pheroze Tamboli, Dolores Lopez-Terrada, Maria Picken, Marileila Garcia, Asha S. Multani, Sen Pathak, Christopher G. Wood, Nizar M. Tannir
Journal: Clinical Cancer Research (2013)

Translocation renal cell carcinoma (tRCC) is a rare subtype of kidney cancer involving the TFEB/TFE3 genes. We aimed to investigate the genomic and epigenetic features of this entity.
Shaping your past selves
Authors: Jeanne Peijnenburg
Journal: Behavioral and Brain Sciences (2005)

I propose to complement Ainslie's idea of “bargaining with your future selves” with that of “shaping your past selves.” The result of such a complementation is that an action can work in two ways: (1) as a predecent for future behavior and (2) as a shaper of past behavior. I argue that this diminishes the unwanted effects of hyperbolic discounting even further.
Adjuvant chemotherapy with 5-fluorouracil, L-folinic acid and levamisole for patients with colorectal cancer: Non-randomised comparison of weekly versus four-weekly schedules — less pain, same gain
Authors: D.J. Kerr, R. Gray, C. McConkey, J. Barnwell
Journal: Annals of Oncology (2000)

QUASAR is a large trial of adjuvant chemotherapy for colorectal cancer in which clinicians could choose to deliver a standard adjuvant cytotoxic chemotherapy regimen, 5-fluorouracil (5-FU) and L-folinic acid (L-FA), in either a once-weekly or a four-weekly schedule. We report results of a non-randomised comparison between these schedules with respect to survival, recurrence and differential toxicity.In a factorial (2 x 2) trial design, QUASAR compared high-dose (175 mg) versus low-dose (25 mg) L-FA and levamisole versus placebo. The dose of 5-FU was fixed at 370 mg/m2 and although the recommended schedule was i.v. bolus delivery, daily for 5 days repeated four-weekly for 6 months, a significant proportion of randomising clinicians were constrained to deliver once-weekly 5-FU-L-FA for 30 weeks.Four thousand nine hundred twenty-seven patients were entered into QUASAR between May 1994 and October 1997, eighteen hundred twenty-nine of whom have recurred and sixteen hundred eighty-nine died. Similar numbers 2370 vs. 2559 were treated with the once-weekly and four-weekly schedules and the demographic features of the 2 groups were well balanced: stage C, 73.3% once-weekly vs. 71.0% four-weekly; colon, 68.0% vs. 68.3%; high-dose FA, 50.1% vs. 49.9%; levamisole, 49.3% vs. 49.3%; females, 40.2% vs. 41.7%; median age (years) 62 vs. 61. The risk of recurrence and survival were similar regardless of schedule: three-year survival was 70.6% once-weekly vs. 71.0% four-weekly; three-year recurrence risk was 35.6% once-weekly vs. 35.5% four-weekly; But, the once-weekly regimen was much less toxic: number of patients for whom toxicity was reported (once-weekly: four-weekly), stomatitis, 37 vs. 337; diarrhoea, 260 vs. 440; neutropenia, 20 vs. 153.The once-weekly regimen is much less toxic than and, apparently, about as effective as the four-weekly schedule. This suggests that the toxicity of 5-FU-L-FA adjuvant chemotherapy could be reduced substantially by weekly scheduling without compromising efficacy. Alternatively, efficacy might be enhanced with equal toxicity by more dose-intense weekly FU-L-FA regimens. However, this conclusion from a non-randomised comparison needs confirmation in prospective randomised studies.
Acute hepatitis C: Dosage and compliance
Authors: Francesco De Rosa, Giuseppe Cariti, Giovanni Di Perri
Journal: Hepatology (2006)

The HEP-NET study recently published in HEPATOLOGY1 showed that a 24-week course of PEG-IFN (1.5 μg/Kg/weekly) alpha-2b was associated with a SVR of 71% in patients with acute hepatitis C (AHC). Treatment was initiated after spontaneous viral clearance ("late-treatment") was excluded and the SVR rate was similar to that we achieved with a 12-week regimen of PEG-IFN alpha-2b administered without waiting for the spontaneous viral clearance ("early treatment").2 Compliance in the HEP-NET study was a major issue and we would like to comment on the early and late treatment strategies of AHC. In our study, including 19 patients of whom 14 were asymptomatic and 11 patients were infected with genotype 1, the SVR was dosage-dependent as it was significantly associated by multivariate analysis only with PEG-IFN at a dosage ≥1.33 μg/Kg/weekly.2 The SVR rate was 74%; 100% and 83.3%, respectively, in genotype 1 and non–1 infected patients treated with a dosage ≥1.33 μg/Kg. Treatment was administered within 34 days (range: 7-116) of the ALT level peak, and the majority of patients were intravenous drug users (IVDUs). Observations from these two studies show that a SVR is significantly associated with high PEG-IFN dosage in early treatment whereas the SVR may be significantly affected by the compliance in late treatment. Moreover, the effectiveness of late treatment administered for 8, 12 and 24 weeks was investigated in another study recently published in HEPATOLOGY and showed that the SVR rate increased with the duration of treatment.3 The SVR rates, when AHC was treated for 8, 12 and 24 weeks, were 67.6%, 82.4% and 91.2%, respectively. Further proof of the importance for early treatment is that negative plasma HCV-RNA was observed 2.5 weeks after the beginning of treatment. We believe this length of time may be shortened since our patients received a variable dosage of PEG-IFN ranging from 1.06 to 1.66 μg/Kg/weekly.4 The less time needed to clear HCV-RNA, the lower the intrahepatic viral load. These studies may not indicate the best choice between early or late treatment strategies. However, we all know that compliance is a major issue in IVDUs as most of them do not understand the reasons to wait for a possible spontaneous viral clearance. Therefore, we believe that the benefits of early treatment with high PEG-IFN dosages are greater than those achievable by the late treatment, especially in IVDUs. Francesco De Rosa*, Giuseppe Cariti*, Giovanni Di Perri*, * Clinica Malattie Infettive, Ospedale Amedeo di Savoia, Corso Svizzera, Turin, Italy.
Clinical comorbidity in patients with osteoarthritis: a case-control study of general practice consulters in England and Wales
Authors: U T Kadam
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objectives:</b> To determine patterns of clinical comorbidity in general practice consulters with OA and compare them with comorbidity in consulters without OA. <b>Methods:</b> A case-control study nested in a one-year prevalence survey of consultations in 60 general practices in England and Wales. Cases were 11 375 subjects aged 50 and over who had consulted with OA during the study year. Controls were 11 780 subjects matched for age and sex who had consulted during the study year, but not for OA. Morbidity outcomes were based on a standard clinical classification system. <b>Results:</b> After adjusting for age, sex, and social class, cases were significantly more likely to have high levels of comorbidity than controls (2.35; 2.16 to 2.55). Significant OA comorbid associations with other musculoskeletal conditions included arthropathies (OR 2.26; 99% CI 1.50 to 3.41), upper limb sprain (2.04; 1.38 to 3.00), synovial and tendon disorders (2.03; 1.54 to 2.68), and other joint disorders (2.00; 1.71 to 2.32). OA non-musculoskeletal associations were with obesity (2.25; 1.73 to 2.92), gastritis (1.98; 1.46 to 2.68), phlebitis (1.80; 1.28 to 2.52), diaphragmatic hernia (1.80; 1.29 to 2.51), ischaemic heart disease (1.73; 1.13 to 2.66) and intestinal diverticula (1.63; 1.20 to 2.23). <b>Conclusions:</b> Comorbidity for OA was extensive, with musculoskeletal as well as non-musculoskeletal conditions. Age, sex, and social class did not explain this comorbidity but propensity to consult may be a part explanation. An important question remains as to whether comorbidity in general practice significantly adds to the disability or further impairs the health of patients with OA.
Stromally Derived Lysyl Oxidase Promotes Metastasis of Transforming Growth Factor-β–Deficient Mouse Mammary Carcinomas
Authors: Michael W. Pickup, Hanane Laklai, Irene Acerbi, Philip Owens, Agnieszka E. Gorska, Anna Chytil, Mary Aakre, Valerie M. Weaver, Harold L. Moses
Journal: Cancer Research (2013)

Abstract The tumor stromal environment can dictate many aspects of tumor progression. A complete understanding of factors driving stromal activation and their role in tumor metastasis is critical to furthering research with the goal of therapeutic intervention. Polyoma middle T-induced mammary carcinomas lacking the type II TGF-β receptor (PyMTmgko) are highly metastatic compared with control PyMT-induced carcinomas (PyMTfl/fl). We hypothesized that the PyMTmgko-activated stroma interacts with carcinoma cells to promote invasion and metastasis. We show that the extracellular matrix associated with PyMTmgko tumors is stiffer and has more fibrillar collagen and increased expression of the collagen crosslinking enzyme lysyl oxidase (LOX) compared with PyMTfl/fl mammary carcinomas. Inhibition of LOX activity in PyMTmgko mice had no effect on tumor latency and size, but significantly decreased tumor metastasis through inhibition of tumor cell intravasation. This phenotype was associated with a decrease in keratin 14–positive myoepithelial cells in PyMTmgko tumors following LOX inhibition as well as a decrease in focal adhesion formation. Interestingly, the primary source of LOX was found to be activated fibroblasts. LOX expression in these fibroblasts can be driven by myeloid cell-derived TGF-β, which is significantly linked to human breast cancer. Overall, stromal expansion in PyMTmgko tumors is likely caused through the modulation of immune cell infiltrates to promote fibroblast activation. This feeds back to the epithelium to promote metastasis by modulating phenotypic characteristics of basal cells. Our data indicate that epithelial induction of microenvironmental changes can play a significant role in tumorigenesis and attenuating these changes can inhibit metastasis. Cancer Res; 73(17); 5336–46. ©2013 AACR.
Combining Simvastatin with the Farnesyltransferase Inhibitor Tipifarnib Results in an Enhanced Cytotoxic Effect in a Subset of Primary CD34+ Acute Myeloid Leukemia Samples
Authors: Karen van der Weide, Susan D.P.W.M. de Jonge-Peeters, Folkert Kuipers, Elisabeth G.E. de Vries, Edo Vellenga
Journal: Clinical Cancer Research (2009)

To show whether the inhibitory effects of the cholesterol synthesis inhibitor simvastatin on human CD34(+) acute myeloid leukemia (AML) cells can be further promoted by combining it with the farnesyltransferase inhibitor tipifarnib.Normal CD34(+), AML CD34(+), and CD34(-) sorted subfractions, and AML cell lines (TF-1 and KG1A) were exposed to simvastatin and tipifarnib.Both simvastatin and tipifarnib showed a cytotoxic effect on AML cell lines, which was additive when used in combination. In primary sorted CD34(+) AML cells, a heterogeneous response pattern was observed upon treatment with simvastatin when analyzing cell survival. A group of normal (n = 12) and abnormal (n = 10) responders were identified within the AML CD34(+) subfraction when compared with normal CD34(+) cells. This distinction was not observed within the AML CD34(-) cell fraction. When the CD34(+) AML cells were exposed to simvastatin and tipifarnib, a significant enhanced inhibitory effect was shown exclusively in the normal AML responder group, whereas the AML CD34(-) cell fractions all showed an enhanced inhibitory effect. The observed heterogeneity in AML responsiveness could not be explained by differences in effects on cholesterol metabolism genes or extracellular signal-regulated kinase phosphorylation in response to simvastatin and tipifarnib treatment.The results suggest that combined treatment with statins and farnesyltransferase inhibitors may be beneficial for a subset of AML patients that can be defined by studying the AML CD34(+) fraction.
Human anti-phosphorylcholine antibodies share idiotopes and are self-binding.
Authors: R Halpern, S V Kaveri, H Köhler
Journal: Journal of Clinical Investigation (1991)

We have previously shown that BALB/c antipneumococcal polysaccharide antibodies with phosphorylcholine (PC) specificity are self-binding, mediated by hypervariable sequence structure of the heavy chain. We extended the observation of self-binding anti-PC antibodies to naturally occurring human anti-PC antibodies. Anti-PC antibodies were purified from normal donor sera and shown to bind to monoclonal antiidiotypic anti-T15 antibodies originally raised against the murine T15 idiotype. These human antibodies are self-binding which is inhibitable by the PC hapten and the murine T15 (50-73)-derived Vh peptide. The anti-PC antibodies were further separated into id-positive and id-negative anti-PC antibodies. Only the T15 id-positive preparation was self-binding. These findings demonstrate an evolutionary, conserved biological property between mouse and man associated with a naturally occurring antibacterial antibody. This conserved biological and structural property may have been selected in evolution because it is part of an important immune defense mechanism against bacterial and other environmental pathogens.