tbuckley/cabot-search huggingface dataset:
Safety of fibreoptic bronchoscopy in asthmatic and control subjects and effect on asthma control over two weeks.
Authors: M. Humbert, D. S. Robinson, B. Assoufi, A. B. Kay, S. R. Durham
Journal: Thorax (1996)

BACKGROUND: Concerns remain about the safety of bronchoscopy in asthma and there are few data on the effect of this procedure on asthma control in the days or weeks following bronchoscopy. METHODS: In an initial study of bronchoalveolar lavage and bronchial biopsies in asthmatic and control subjects, data on peak expiratory flow rates (PEFR) collected prospectively before and after the procedure were available from 21 of the 29 asthmatic subjects studied. These showed a median 23% fall in PEFR from baseline after bronchoscopy (range 3-58%). To determine whether this fall in PEFR following bronchoscopy reflected bronchospasm or the effect of sedation, PEFR and spirometric tests were performed during the two hours following bronchoscopy in a further study of 15 symptomatic asthmatic subjects and 20 non-asthmatic controls. To examine the effect on asthma control, asthmatic patients recorded PEFR, symptom scores, and medication use for two weeks before and after bronchoscopy. RESULTS: After bronchoscopy with bronchial biopsies there was no difference between the median maximal fall in either PEFR or arterial oxygen saturation between the 15 asthmatic patients (10.4% and 4%, respectively) and 20 controls (12% and 3%). Moreover, there were no significant changes in PEFR, symptom score, or medication use by the asthmatic subjects in the two weeks after bronchoscopy when compared with the two weeks before bronchoscopy. CONCLUSIONS: Fibreoptic bronchoscopy is well tolerated in asthmatic subjects. Falls in PEFR in both asthmatic and non-asthmatic subjects after bronchial biopsy may reflect the effects of sedation rather than bronchospasm. Additional bronchoalveolar lavage may cause bronchoconstriction. Careful monitoring is therefore essential. Peak flow monitoring up to two weeks after bronchoscopy with bronchial biopsy revealed no delayed effects on asthma control.
The Swedish Registry of Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (GallRiks)
Authors: Lars Enochsson, Anders Thulin, Johanna Österberg, Gabriel Sandblom, Gunnar Persson
Journal: JAMA Surgery (2013)

<h3>Objectives</h3>To describe the process of initiating and organizing a nationwide validated web-based quality registry of gallstone surgery and endoscopic retrograde cholangiopancreatography (ERCP) and to present some clinical data and the impact the registry has had on the clinical treatment of gallstones.<h3>Design</h3>Observational, population-based registry study.<h3>Setting</h3>Data from the nationwide Swedish Registry of Gallstone Surgery and ERCP (GallRiks).<h3>Patients</h3>From May 1, 2005, to December 31, 2011, 63 685 cholecystectomies (laparoscopic and open) and 37 860 ERCPs have been prospectively registered in GallRiks.<h3>Interventions</h3>Cholecystectomies, laparoscopic or conventional, as well as ERCP in a population-based setting.<h3>Main Outcome Measures</h3>Registrations of all cholecystectomies and ERCPs are performed online by the surgeon or endoscopist. Thirty-day follow-up of both gallstone surgery and ERCP is mandatory, as is an additional 6-month follow-up of the cholecystectomies. Scores on the 36-Item Short Form Health Survey are registered preoperatively and 6 months postoperatively in elective cholecystectomies at selected units.<h3>Results</h3>The 30-day overall complication rate is 6.1% in elective cholecystectomy, 11.2% in urgent cholecystectomy, and 12.0% following ERCP. The use of antibiotic and thromboembolic prophylaxis in elective laparoscopic cholecystectomy in Sweden has decreased by 8.7% and 17.8% (2006-2011), respectively, mainly owing to presentation of GallRiks data both at meetings and published in peer-reviewed publications. The large database has also enabled several research projects, including one demonstrating that the intention to perform intraoperative cholangiography reduced the risk of death after cholecystectomy. The database has reached greater than 90% national coverage and is continuously validated.<h3>Conclusions</h3>GallRiks is a validated national quality registry for gallstone surgery and ERCP, serving as a base for audit of gallstone disease treatment. It also provides a database for clinical research.
Changing places to study the medium-term effects of air pollution
Authors: Lidia Casas, Hans Scheers, Tim Nawrot, Ben Nemery
Journal: European Respiratory Journal (2014)

As part of a panel study on medium-term effects of air pollution, we evaluated the association between exposure to PM10 and NO2 and the intra-individual changes in FEV1 and FVC. Twenty healthy volunteers aged 59 to 76 years underwent 4 health exams (n=80 observations) over 1.5 months. The first and last exams were performed in Leuven (Belgium), the other during a 10 day stay in Milan (Italy). Spirometry was done with NDD EasyOne. PM10 lag0, lag1 and the average for lag0, lag1 and lag2 (av0-2) were obtained from local monitoring stations. Personal exposure to NO2 was monitored 3 times during 5 days. We built generalised linear mixed models to obtain adjusted coefficients (β) and their 95% confidence intervals (CI), indicating a change in FEV1 or FVC (mL) per 10 μg/m³ change in PM10 or NO2. Adjusting variables were sex, age, height, weight, temperature and humidity.

In Milan, lung volumes were lower (FEV1 crude (c) β=-39 CI: -92; 14; FVC cβ=-43 CI: -102; 16), and exposure levels higher (PM10 av0-2 cβ=19 CI: 16; 21; NO2 cβ=33 CI: 31; 35). After adjustment, a 10 μg/m³ increase in av0-2 was associated with a 65 mL decline in FVC (CI:-120;-10). Interaction terms for sex and PM10 or NO2 were significant (p<0.05). Stratified analyses showed that PM10 and NO2 levels in men but not women were associated with FEV1 and FVC decline. In men, the β was lowest for FVC vs av0-2 (β=-133 CI: -214;-52), and a 10 μg/m³ increase in NO2 was associated with a 37 mL decline in FEV1 (CI: -63; -11) and 34 mL in FVC (CI: -66; -2).

Our results suggest that medium-term changes in PM10 and NO2 are associated with a decline in lung function and that sex is an effect modifier that needs to be considered in further analyses.
Lineage Commitment in the Thymus: Only the Most Differentiated (TCRhibcl-2hi) Subset of CD4+CD8+Thymocytes Has Selectively Terminated CD4 or CD8 Synthesis
Authors: Jennifer A. Punt, Harumi Suzuki, Larry G. Granger, Susan O. Sharrow, Alfred Singer
Journal: The Journal of Experimental Medicine (1996)

Lineage commitment is a developmental process by which individual CD4+CD8+ (double positive, DP) thymocytes make a decision to differentiate into either CD4+ or CD8+ T cells. However, the molecular event(s) that defines lineage commitment is controversial. We have previously proposed that lineage commitment in DP thymocytes can be molecularly defined as the selective termination of CD4 or CD8 coreceptor synthesis. The present study supports such a molecular definition by showing that termination of either CD4 or CD8 synthesis is a highly regulated event that is only evident within the most differentiated DP subset (CD5hiCD69hiTCRhibcl-2hi). In fact, essentially all cells within this DP subset actively synthesize only one coreceptor molecule. In addition, the present results identify three distinct subpopulations of DP thymocytes that define the developmental progression of the lineage commitment process and demonstrate that lineage commitment is coincident with upregulation of TCR and bcl-2. Thus, this study supports a molecular definition of lineage commitment and uniquely identifies TCRhibcl-2hi DP thymocytes as cells that are already committed to either the CD4 or CD8 T cell lineage.
Influence of the pattern of admission on the outcome of patients admitted to a respiratory intensive care unit: Does the step-down pathway differ from the step-up one?
Authors: Ilaria Valentini, AngelaMariaGrazia Pacilli, Paolo Carbonara, Rita Vitale, Laura Castaldi, Luca Fasano, Stefano Nava
Journal: European Respiratory Journal (2012)

The influence of the location prior to the admission in a Respiratory Intensive Care Unit (RICU) on the patients' outcome has never been assessed. We have evaluated the clinical outcomes and prognostic indices, according to their provenience, in 175 consecutive patients admitted over 1-year period in our RICU. 37% of the patients were admitted directly from the Emergency Room (ER), 27% from one of the Intensive Care Units (ICUs)within our hospital, 18% from our Respiratory ward (RW) and 18% transferred from other medical wards(OWs). Patients transferred from our RW had a significantly higher SAPSII score (44±10 vs 34±13,33±13 and 41±14, for ER,ICUs and OWs, respectively), a lower albumin (2.9±0.5 vs 3.2±0.6 and 3.6±0.5 for ICUs and ER, respectively). All the other clinical variables were similar except for CHF that was lower in those patients admitted from the ICUs. Mortality rate was significantly higher in the patients transferred from our RW and OWs (15%,18%,38%,43% for ER,ICUs,OWs and RW, respectively). A Cox multivariate analysis and the mortality risk (Hazard ratio) showed that an high SAPS II score (p<0.0114), low blood albumin levels (p<0.0216), non invasive mechanical ventilation (NIV) (p<0.004) and congestive heart failure (p<0.0481) were significantly associated with the mortality rate. In conclusion, when our RICU acts as “step-down” the mortality rate is lower than when it acts as “step-up”, probably because these latter patients are admitted in end-stage conditions. NIV was surprisingly correlated with an high mortality risk, because in a large subset of patients it was used as ceiling treatment.
Suppression of Nonhomologous End Joining Repair by Overexpression of HMGA2
Authors: Angela Y.J. Li, Lee Ming Boo, Shih-Ya Wang, H. Helen Lin, Clay C.C. Wang, Yun Yen, Benjamin P.C. Chen, David J. Chen, David K. Ann
Journal: Cancer Research (2009)

Abstract Understanding the molecular details associated with aberrant high mobility group A2 (HMGA2) gene expression is key to establishing the mechanism(s) underlying its oncogenic potential and effect on the development of therapeutic strategies. Here, we report the involvement of HMGA2 in impairing DNA-dependent protein kinase (DNA-PK) during the nonhomologous end joining (NHEJ) process. We showed that HMGA2-expressing cells displayed deficiency in overall and precise DNA end-joining repair and accumulated more endogenous DNA damage. Proper and timely activation of DNA-PK, consisting of Ku70, Ku80, and DNA-PKcs subunits, is essential for the repair of DNA double strand breaks (DSB) generated endogenously or by exposure to genotoxins. In cells overexpressing HMGA2, accumulation of histone 2A variant X phosphorylation at Ser-139 (γ-H2AX) was associated with hyperphosphorylation of DNA-PKcs at Thr-2609 and Ser-2056 before and after the induction of DSBs. Also, the steady-state complex of Ku and DNA ends was altered by HMGA2. Microirradiation and real-time imaging in living cells revealed that HMGA2 delayed the release of DNA-PKcs from DSB sites, similar to observations found in DNA-PKcs mutants. Moreover, HMGA2 alone was sufficient to induce chromosomal aberrations, a hallmark of deficiency in NHEJ-mediated DNA repair. In summary, a novel role for HMGA2 to interfere with NHEJ processes was uncovered, implicating HMGA2 in the promotion of genome instability and tumorigenesis. [Cancer Res 2009;69(14):5699–706]
Accelerated Approval and Breakthrough Therapy Designation: Oncology Drug Development on Speed?
Authors: James C. Yao, Funda Meric-Bernstam, J. Jack Lee, S. Gail Eckhardt
Journal: Clinical Cancer Research (2013)

Recent advances in biotechnology have led to discoveries resulting in major improvements in the therapy of refractory malignancies, although most advanced cancers remain incurable. Thus, there is global consensus around the need to streamline the drug approval process for effective agents. Accelerated Approval and Breakthrough Therapy Designation hold the promise of making new treatments available sooner through the use of smaller studies using intermediate endpoints. Here, we consider the inherent limitations of smaller studies and discuss the strategies for hastening oncology drug development while maintaining high-efficacy standards.
Is hip arthroscopy for femoroacetabular impingement only for athletes?
Authors: Ajay Malviya, Giles H Stafford, Richard N Villar
Journal: British Journal of Sports Medicine (2012)

Purpose The aim of this study was to compare the outcome of hip arthroscopy for femoroacetabular impingement (FAI) between athletes and non-athletes. Methods The authors prospectively collected data on 122 patients, the largest comparative series reported, who underwent hip arthroscopy for FAI. Of these, 80 actively participated in sporting activities (athletes), while 42 did not (non-athletes). Patients were asked to complete questionnaires for the modified Harris hip score (MHHS), non-arthritic hip score (NAHS), patient satisfaction on a visual analogue scale (VAS). This was collected immediately before surgery, and at 6 weeks, 6 months and 1 year after the procedure. The responses to the MHHS questionnaire were used to calculate the quality-of-life (QoL) score using the Rosser index matrix. Results A significant improvement in the MHHS, NAHS and QoL was observed at 6 weeks, 6 months and 1 year after surgery (p&lt;0.001). The 6-week MHHS (p=0.01) and NAHS (p=0.04) for the athletes were significantly better as compared with non-athletes. However, the 6-month and 1-year MHHS, NAHS and QoL scores were statistically similar for both groups. Conclusions In this large, prospective series of patients we have demonstrated the positive impact of arthroscopic surgery for FAI in both the athletic and non-athletic population. Arthroscopic management of FAI is thus not the sole domain of the athletic patient. Non-athletes can do just as well.
Multiple haematological malignancies in a patient with rheumatoid arthritis without exposure to disease modifying therapy
Authors: H Piper
Journal: Annals of the Rheumatic Diseases (2006)

Rheumatoid arthritis (RA) may be associated with an increased risk of haematological malignancy, perhaps as a result of RA itself or of its treatment. We describe the unusual case of a patient with longstanding RA who developed both lymphoproliferative and myeloproliferative malignancy without exposure to disease modifying drugs.

A 64 year old woman, wheelchair dependent with spina bifidar related spastic paraparesis, had seropositive RA never treated with disease modifying drugs. In 1993, she developed Philadelphia chromosome positive, chronic myelogenous leukaemia (CML), treated with busulfan, initially 2 mg daily and subsequently on alternate days. Within 3 months, her total white cell count normalised and busulfan was discontinued. No further treatment was required for the CML.

Over subsequent years she required increasing support, including inpatient care, for immobility due to spina bifida, …
Nilotinib in patients with Ph+ chronic myeloid leukemia in accelerated phase following imatinib resistance or intolerance: 24-month follow-up results
Authors: P D le Coutre, F J Giles, A Hochhaus, J F Apperley, G J Ossenkoppele, R Blakesley, Y Shou, N J Gallagher, M Baccarani, J Cortes, H M Kantarjian
Journal: Leukemia (2011)
When nurture becomes nature: Ethnocentrism in studies of human development
Authors: David F. Lancy
Journal: Behavioral and Brain Sciences (2010)

This commentary will extend the territory claimed in the target article by identifying several other areas in the social sciences where findings from the WEIRD population have been over-generalized. An argument is made that the root problem is the ethnocentrism of scholars, textbook authors, and social commentators, which leads them to take their own cultural values as the norm.
Leukocyte Activation and Flow Behavior in Rat Skeletal Muscle in Sepsis
Authors: RICHARD D. PIPER, MICHELLE L. PITT-HYDE, LORI A. ANDERSON, WILLIAM J. SIBBALD, RICHARD F. POTTER
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

In animal models of endotoxemia, sepsis is associated with the accumulation of leukocytes and altered microvascular perfusion. In order to test the hypothesis that bacterial sepsis upregulates leukocyte–endothelial adhesion, we used intravital microscopy to examine the flow behavior of leukocytes in the postcapillary venules (PCV) of rats made septic by cecal ligation and perforation (CLP). Animals were randomized to CLP or sham study groups and studied 6 h, 24 h, or 48 h later. In postcapillary venules of the extensor digitorum longus muscle, we found that: (1) over the course of the study, leukocyte adhesion and extravasation increased in both experimental groups (analysis of variance [ANOVA], significant time effect: adhesion, p < 0.001; extravasation, p < 0.05); (2) leukocyte adhesion was decreased by CLP treatment (ANOVA, sepsis effect, p = 0.05), particularly after 24 to 48 h of sepsis (ANOVA, sepsis × time interaction, p < 0.05); and (3) the reduction in leukocyte adhesion in CLP animals was associated with a decrease in leukocyte extravasation (ANOVA, sepsis effect, p < 0.01). After correction for the reduction in systemic leukocyte count associated with CLP, the effect of sepsis on leukocyte adhesion and extravasation no longer reached statistical significance. These findings suggest that chronic (6 to 48 h) bacterial sepsis does not upregulate leukocyte adhesion in a manner similar to that seen in models of acute endotoxemia. These data suggest that the increased microcirculatory flow heterogeneity seen in this and other models of bacterial sepsis may not be explained by leukocyte entrapment in postcapillary venules.
<i>In vivo</i> Dynamics of Stable Chronic Lymphocytic Leukemia Inversely Correlate with Somatic Hypermutation Levels and Suggest No Major Leukemic Turnover in Bone Marrow
Authors: Rogier van Gent, Arnon P. Kater, Sigrid A. Otto, A. Jaspers, José A.M. Borghans, Nienke Vrisekoop, Mariëtte A.T. Ackermans, An F.C. Ruiter, Shulamiet Wittebol, Eric Eldering, Marinus H.J. van Oers, Kiki Tesselaar, Marie José Kersten, Frank Miedema
Journal: Cancer Research (2008)

Abstract Although accumulating evidence indicates that chronic lymphocytic leukemia (CLL) is a disease with appreciable cell dynamics, it remains uncertain whether this also applies to patients with stable disease. In this study, 2H2O was administered to a clinically homogeneous cohort of nine stable, untreated CLL patients. CLL dynamics in blood and bone marrow were determined and compared with normal B-cell dynamics in blood from five healthy individuals who underwent a similar 2H2O labeling protocol. Average CLL turnover rates (0.08–0.35% of the clone per day) were ∼2-fold lower than average B-cell turnover rates from healthy individuals (0.34–0.89%), whereas the rate at which labeled CLL cells in blood disappeared (0.00–0.39% of B cells per day) was ∼10-fold lower compared with labeled B cells from healthy individuals (1.57–4.24% per day). Leukemic cell turnover variables inversely correlated with the level of somatic hypermutation of the CLL clone (IgVH mutations). Although CLL cells in bone marrow had a higher level of label enrichment than CLL cells in blood, no difference between proliferation rates and proapoptotic and antiapoptotic profiles of CLL cells from these compartments was observed. These data suggest that, in stable disease, there is a biological relationship between the degree of somatic hypermutation of the CLL clone and its dynamics in vivo. Furthermore, in contrast to lymph nodes, the bone marrow does not seem to be a major CLL proliferation site. [Cancer Res 2008;68(24):10137–44]
Significance of emphysema observed on computed tomography scan in asthma
Authors: F Paganin, D Jaffuel, J Bousquet
Journal: European Respiratory Journal (1997)

Computed tomography (CT) scan has been used in the diagnosis of airways diseases [1] because of the high degree of anatomical detail provided. Most abnormalities, such as bronchiectasis and emphysema, seen on a CT scan have been anatomically validated, but their clinical significance is not always fully understood. Highresolution CT (HR-CT) has been used to study asthmatics [2‐8]. It has been consistently observed that more abnormalities related to fixed airways remodelling, such as bronchial dilatation and bronchiectasis are observed in asthmatic subjects than in normal subjects, although the clinical consequences of these findings are not clear. HRCT scans have also been used to measure the internal size of the airways at baseline, during challenge or after bronchodilatation [9‐12]. However, there is no data on lung density in patients with acute and chronic asthma. This was the aim of the paper published in the present issue of the European Respiratory Journal [13]. The relationship between asthma and emphysema was suggested in 1952 by ROYLE [14] who found emphysema in patients with severe asthma. However, the study was flawed since chest radiographs failed to recognize mild emphysema [15] and most of the patients studied were current or exsmokers. Importance of CT scan in the diagnosis of emphysema Pulmonary emphysema is a pathological diagnosis, but correlations between results of lung function tests and the extent of emphysema are poor. Lung function tests are also nonspecific for emphysema, and alteration of transfer factor of the lung for carbon monoxide (TL,CO) may be due to cardiogenic oedema or interstitial disease. The diagnosis of pulmonary emphysema can be made with relative confidence on the basis of clinical and radiological criteria. Despite the fact that very mild emphysema goes undetected and the severity of the disease may be underestimated, HR-CT is the most sensitive radiographic method with which to image emphysema and has been shown to be more sensitive than pulmonary function tests or TL,CO [15‐18]. Many studies have demonstrated significant correlations between CT scan data and pathological observations of lungs obtained at autopsy or after surgery for both centrilobular and panacinar emphysema [19‐23]. However, occasionally CT scans give false-positive findings and the criteria used