tbuckley/cabot-search huggingface dataset:
Noninvasive ventilation in cystic fibrosis: the Italian physiotherapists' point of view: Figure 1–
Authors: Sergio Zuffo, Simone Gambazza, Alessandro Capra
Journal: European Respiratory Journal (2012)

in its management.According to respondents, NIV was the first-line treatment to improve gas exchange (89%) and was a valid tool as support to clearance techniques (68%) and to exercise training (43%).The main criteria to propose NIV, according to physiotherapists who use NIV (n528), were hypercapnic pulmonary exacerbation, awaiting lung transplantation, severe impairment of pulmonary function and difficulties experienced with clearing secretions (fig.1).Almost all interviewees agreed that NIV was part of the ''core competence'' for physiotherapists who work in CF centres (95%) and clinics (85%).A detailed picture revealed that 71% (n520) of them chose ventilators, 96% were involved in the crucial choice of interfaces and 75% were in charge of ventilator settings.The majority (93%) took care of patients' comfort and compliance enhancement and set frequent follow-ups to periodically review patients and, thus, improve their adherence.Although there are some limitations, this is the first Italian study that explores how physiotherapists are involved in the NIV management in CF centres and their expectations and beliefs about the benefits of NIV.Despite the absence of standard protocols and guidelines, Italian CF centres and clinics take into consideration the therapeutic use of NIV and physiotherapists are involved in its use.According to our results, the rationale of adopting NIV as a therapeutic choice in CF as perceived by physiotherapists is in line with what the literature has recently suggested [5].Harmonising the core competencies of physiotherapists all over Italy and the NIV management of CF patients is, however, still urgently needed.
Abstract B26: Non-catalytic effects of PARP inhibitors in the context of cell cycle and homology-directed DNA damage repair
Authors: Petar Jelinic, Douglas A. Levine
Journal: Clinical Cancer Research (2013)

Abstract Background: Poly (ADP)-ribose polymerase inhibitors (PARPis) target PARPs, the stress sensing proteins that respond to DNA single-strand breaks. PARP inhibition has been extensively explored in pre-clinical and clinical studies with successes demonstrated in homology-directed DNA damage repair (HDR) pathway-deficient ovarian cancer patients. The inhibitory potential of PARPis is well established; however non-catalytic effects that may add to their therapeutic properties are not fully understood. Our objective was to comparatively evaluate non-catalytic inhibitory properties, particularly in the context of cell cycle and HDR, of the most widely tested PARPis in pre-clinical and clinical studies, olaparib and veliparib. Methods: To measure DNA damage repair activity upon PARPi treatment, we used a well-established DR-GFP reporter assay in two model cell lines, U2OSDR-GFP and H1299DR-GFP. Cell cycle progression was assessed by staining with propidium iodide and monitored by flow cytometry. Depletion of p53 in U2OSDR-GFP cells was performed by standard siRNA knock-down technique using electroporation for transfection. Immunoblotting was used to confirm cell cycle results and demonstrate replicative stress on the protein expression levels. Results: We found a dramatic decrease in DNA damage repair activity in olaparib versus veliparib-treated U2OSDR-GFP cells, regardless of their inhibitory potency. This decrease in HDR activity was a result of olaparib triggering a cell cycle arrest-like state as a response to strong replicative stress. Lack of the same effect in p53-null H1299DR-GFP cells suggests that olaparib's effect is p53-dependent, which was confirmed in U2OSDR-GFP cells depleted of p53. Our data also suggest that cells treated with veliparib are more ambivalent towards p53 status, a difference in comparison to olaparib-treated cells. Conclusion: These data demonstrate that olaparib and veliparib differ in their non-catalytic inhibitory effects, with olaparib but not veliparib mitigating DNA damage repair activity via cell cycle arrest-like effects in a p53-WT background. This new insight into olaparib's and veliparib's mechanism of action should be considered when developing inclusion criteria for treatment of ovarian cancer patients with these PARP inhibitors or others. Citation Format: Petar Jelinic, Douglas A. Levine. Non-catalytic effects of PARP inhibitors in the context of cell cycle and homology-directed DNA damage repair. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr B26.
P71. Adoptive transfer of TCR gene-transduced lymphocytes targeting MAGE-A4 for refractory esophageal cancer
Authors: H Shiku, H Ikeda, Y Miyahara, M Ishihara, N Katayama, D Tomura, I Nukaya, J Mineno, K Takesako, S Kageyama
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Engineering the antigen receptor gene in patients' lymphocytes is one promising strategy to create antigen-specific lymphocytes without senescent phenotypes. The strategy provides an opportunity to extend the application of adoptive T cell therapy for cancer patients. However,
Modifications in accessibility of membrane glycoproteins, binding of specific ligands and coagulation factor V during the activation of platelets in blood emerging from bleeding time wounds
Authors: Gin�s Escolar, Miguel Lozano, Maribel D�az-Ricart, Gundu H.R. Rao, Antonio Ordinas, James G. White
Journal: American Journal of Hematology (1999)

Dual color flow cytometric techniques were applied to micro-aliquots of whole blood obtained from bleeding time (BT) wounds. Modifications in platelet activation markers (P-selectin [CD62P]) and lysosomal related protein (LIMPS [CD63]), presence of membrane glycoproteins (GPIb [CD42b], GPIIb-IIIa [CD41a], GDIV [CD36], binding of von Willebrand factor (vWF), fibrinogen (Fg) and factor V [FV]) were analyzed in normal donors (n = 10) and in a severe von Willebrand patient (type 3) von Willebrand disease [vWD]). Samples of blood (20 μl) were sequentially removed from BT wound edges for up to 5 min and fixed with paraformaldehyde. Antigens were detected using the corresponding tagged monoclonal antibodies (moAbs) and quantitative results were referred to those found on platelet samples obtained from venous blood obtained from the same individuals. A progressive increase in % of platelets positive for activation dependent antigens (CD62 from 7 ± 2 to 48 ± 19% and CD63 from 9 ± 1 to 44 ± 8%; initial vs. 4 min) was observed. Accessibility of GPIIb-IIIa epitopes on platelets from BT wounds remained slightly above levels observed in venous blood platelets, despite a progressive increase in the presence of platelets positive for Fgn. Binding of MoAb to GPIV increased at late stages of BT. A moderate decrease in the binding of a moAb to GPIb was observed on platelets obtained at late stages of the BT (14 ± 9% and 20 ± 6% at 4 and 5 min, respectively). This apparent decrease in GPIb epitopes paralleled an increased presence of platelets positive for vWF (26 ± 12 and 38 ± 15%). Binding of moAb to GPIb always remained above basal levels in platelets obtained from BTs performed in the patient with type 3 vWD. FV levels on platelets coming from the BT persisted at background levels in all the individuals and at all times studied. Am. J. Hematol. 60:260–267, 1999. © 1999 Wiley-Liss, Inc.
Colonisation with Aspergillus of an intralobar pulmonary sequestration.
Authors: J Freixinet, J de Cos, F Rodriguez de Castro, G Julia, T Romero
Journal: Thorax (1995)

Pulmonary sequestration is a term used to describe an area of embryonic lung tissue supplied by an anomalous systemic artery. Two forms are recognised-extralobar and intralobar-with different clinical presentations. A patient is reported with intralobar pulmonary sequestration in the left lung and colonisation with Aspergillus which was successfully treated by lower lobectomy.
Randomized phase III study of 3-weekly versus weekly docetaxel in pretreated advanced non-small-cell lung cancer: a Spanish Lung Cancer Group trial
Authors: C. Camps, B. Massuti, A. Jiménez, I. Maestu, R. García Gómez, D. Isla, J.L. González, D. Almenar, A. Blasco, R. Rosell, A. Carrato, N. Viñolas, N. Batista, C. García Girón, A. Galán, M. López, R. Blanco, M. Provencio, P. Diz, E. Felip
Journal: Annals of Oncology (2005)
A FRENCH RIVAL TO NAUHEIM: BOURBONLANCY
Authors: J. M. Robertson
Journal: BMJ (1903)

cation which I made about a year ago in Roughton's splint for Pott's fracture.Like Roughton's the splint is made of wood, and is shaped for the outer side of the leg and foot, the oval fenestrum being opposite the external malleolus.But instead of the leg and foot pieces being at right angles they form an acute angle equal to four-fifths of a right angle.In treating Pott's fracture it is taught, that after reducing any displacement, the foot should be flexed at right angles to the leg, an extended or everted position of the foot being avoided.To flex the foot so as to form an acute angle with the leg would appear to be even a better plan.For when the ankle is thus fully flexed the wider anterior part of the astragalus occupies the inter- malleolar space, and thus presses aside any encroaching fragment which may be separated from the inner malleolus, and also prevents reparative material from narrowing the articular cavity.It was to carry out this principle that this splint Was designed.The splint having been evenly padded the limb is fixed to it by strapping, and the tilting of the bottom foot piece maintains not only full flexion of the foot, but also inversion.Massage can be applied as the limb rests on the splint, the knee being well flexed to relax the tendo Achillis, and then, as Pott says, " everything will in general succeed very happily."Treatment of Fracture of the Patella.-Dr.ASHLEY CUMMINS (Cork) has designed the instrument here illustrated, and t-i _ _i R ~~~~~~~~~~~~~~~~~~~~a tstates that he has found it invaluable in the operation for fracture of the patella, by the direct method, because of the great facility with which the wire sutures can be passed.His method is as follows: The solid, curved bradawl is first passed through one fragment of the fracture and then withdrawn.The hollow bradawl, containing a stilette (to prevent the en- trance of particles of bone) is then inserted through the passage made by the solid bradawl.The stilette is with- drawn, and the wire inserted about 1 in., and the bradawl drawn out carrying the wire.The method is repeated on the opposite fragment of bone, the other end of the wire being passed " in.into the hollow bradawl, which is removed, carrying the wire with it.The fragments of bone are then approximated and fixed in the usual way by twisting the wire.The instruments have been made by Messrs.
Iron Status and Hemoglobin Level in Chronic Renal Insufficiency
Authors: Chi-Yuan Hsu, Charles E McCulloch, Gary C Curhan
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Much has been written on the important contribution of iron deficiency toward anemia and epoetin resistance among end-stage renal disease (ESRD) patients, but there are few studies of iron status among chronic renal insufficiency (CRI) subjects not yet requiring dialysis. The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) Practice Guidelines recommend maintaining ferritin ≥100 ng/ml and transferrin saturation (TSAT) ≥20% to ensure adequate iron supply for erythropoiesis among patients with chronic kidney disease, whether or not they are dialysis-dependent. Analysis of the nationally representative data from the Third National Health and Nutrition Examination Survey (NHANES III 1988–1994) revealed that only a minority of anemic CRI subjects in the United States met these K/DOQI targets. For example, in the range of creatinine clearance (CrCl) 30 to 50 ml/min, less than one third of men with hemoglobin &lt;12 g/dl and women with hemoglobin &lt;11 g/dl had ferritin ≥100 ng/ml and TSAT ≥20%. In addition, TSAT levels above 20% were independently associated with higher hemoglobin levels. Such data raise the question whether the K/DOQI targets should be reevaluated. It is concluded that ferritin and TSAT targets derived from ESRD studies may not be applicable to subjects with CRI. Further studies are needed to guide optimization of iron status and hemoglobin level in the much larger CRI population.
Explaining the Increase in Coronary Heart Disease Mortality in Beijing Between 1984 and 1999
Authors: Julia Critchley, Jing Liu, Dong Zhao, Wang Wei, Simon Capewell
Journal: Circulation (2004)

Coronary heart disease (CHD) mortality is rising in many developing countries. We examined how much of the increase in CHD mortality in Beijing, China, between 1984 and 1999 could be attributed to changes in major cardiovascular risk factors and assessed the impact of medical and surgical treatments.A validated, cell-based mortality model synthesized data on (1) patient numbers, (2) uptake of specific medical and surgical treatments, (3) treatment effectiveness, and (4) population trends in major cardiovascular risk factors (smoking, total cholesterol, blood pressure, obesity, and diabetes). Main data sources were the WHO MONICA and Sino-MONICA studies, the Chinese Multi-provincial Cohort Study, routine hospital statistics, and published meta-analyses. Age-adjusted CHD mortality rates increased by approximately 50% in men and 27% in women (1608 more deaths in 1999 than expected by application of 1984 rates). Most of this increase ( approximately 77%, or 1397 additional deaths) was attributable to substantial rises in total cholesterol levels (more than 1 mmol/L), plus increases in diabetes and obesity. Blood pressure decreased slightly, whereas smoking prevalence increased in men but decreased substantially in women. In 1999, medical and surgical treatments in patients together prevented or postponed approximately 642 deaths, mainly from initial treatments for acute myocardial infarction ( approximately 41%), hypertension (24%), angina (15%), secondary prevention (11%), and heart failure (10%). Multiway sensitivity analyses did not greatly influence the results.Much of the dramatic CHD mortality increases in Beijing can be explained by rises in total cholesterol, reflecting an increasingly "Western" diet. Without cardiological treatments, increases would have been even greater.
ROLE OF COMPLEMENT IN INDUCTION OF ANTIBODY PRODUCTION IN VIVO
Authors: M. B. Pepys
Journal: The Journal of Experimental Medicine (1974)

In an in vivo study in mice, suppression by the C3-cleaving protein of cobra venom (CoF), and other C3-reactive agents (zymosan, aggregated IgG, anti-C3 antibodies, and type III pneumococcal polysaccharide) of the thymus-dependent antibody responses to sheep erythrocytes, ovalbumin, and human IgG was demonstrated. The thymus-independent antibody response to polyvinyl-pyrrolidone was however unaffected by CoF. These and other published observations suggest that there may be a requirement for functional C3 in induction of thymus-dependent but not thymus-independent antibody production. A model for the role of C3 in lymphocyte cooperation is proposed based on these data analyzed in the light of existing knowledge of this process. It is postulated that fixed C3 interacting with macrophage See PDF for Structure and B-cell C3 receptors might enhance or facilitate T-dependent presentation of antigen to B cells.
Magnetic resonance elastography is superior to acoustic radiation force impulse for the Diagnosis of fibrosis in patients with biopsy‐proven nonalcoholic fatty liver disease: A prospective study
Authors: Jeffrey Cui, Elhamy Heba, Carolyn Hernandez, William Haufe, Jonathan Hooker, Michael P. Andre, Mark A. Valasek, Hamed Aryafar, Claude B. Sirlin, Rohit Loomba
Journal: Hepatology (2015)

Magnetic resonance elastography (MRE), an advanced magnetic resonance–based imaging technique, and acoustic radiation force impulse (ARFI), an ultrasound‐based imaging technique, are accurate for diagnosing nonalcoholic fatty liver disease (NAFLD) fibrosis. However, no head‐to‐head comparisons between MRE and ARFI for diagnosing NAFLD fibrosis have been performed. We compared MRE versus ARFI head‐to‐head for diagnosing fibrosis in well‐characterized patients with biopsy‐proven NAFLD. This cross‐sectional analysis of a prospective cohort involved 125 patients (54.4% female) who underwent MRE, ARFI, and contemporaneous liver biopsies scored using the Nonalcoholic Steatohepatitis Clinical Research Network histological scoring system. The performances of MRE versus ARFI for diagnosing fibrosis were evaluated using area under the receiver operating characteristic curves (AUROCs). The mean (± standard deviation) age and body mass index were 48.9 (±15.4) years and 31.8 (±7.0) kg/m 2 , respectively. For diagnosing any fibrosis (≥ stage 1), the MRE AUROC was 0.799 (95% confidence interval [CI] 0.723‐0.875), significantly ( P = 0.012) higher than the ARFI AUROC of 0.664 (95% CI 0.568‐0.760). In stratified analysis by presence or absence of obesity, MRE was superior to ARFI for diagnosing any fibrosis in obese patients ( P &lt; 0.001) but not in nonobese patients ( P = 0.722). The MRE AUROCs for diagnosing ≥stages 2, 3, and 4 fibrosis were 0.885 (95% CI 0.816‐0.953), 0.934 (95% CI 0.863‐1.000), and 0.882 (95% CI 0.729‐1.000); and the ARFI AUROCs were 0.848 (95% CI 0.776‐0.921), 0.896 (95% CI 0.824‐0.968), and 0.862 (95% CI 0.721‐1.000). MRE had higher AUROCs than ARFI for discriminating dichotomized fibrosis stages at all dichotomization cutoff points, but the AUROC differences decreased as the cutoff points (fibrosis stages) increased. Conclusion : MRE is more accurate than ARFI for diagnosing any fibrosis in NAFLD patients, especially those who are obese. (H epatology 2016;63:453–461)
Topical and Peripherally Acting Analgesics
Authors: Jana Sawynok
Journal: Pharmacological Reviews (2003)

Acute nociceptive, inflammatory, and neuropathic pain all depend to some degree on the peripheral activation of primary sensory afferent neurons. The localized peripheral administration of drugs, such as by topical application, can potentially optimize drug concentrations at the site of origin of the pain, while leading to lower systemic levels and fewer adverse systemic effects, fewer drug interactions, and no need to titrate doses into a therapeutic range compared with systemic administration. Primary sensory afferent neurons can be activated by a range of inflammatory mediators such as prostanoids, bradykinin, ATP, histamine, and serotonin, and inhibiting their actions represents a strategy for the development of analgesics. Peripheral nerve endings also express a variety of inhibitory neuroreceptors such as opioid, α-adrenergic, cholinergic, adenosine and cannabinoid receptors, and agonists for these receptors also represent viable targets for drug development. At present, topical and other forms of peripheral administration of nonsteroidal anti-inflammatory drugs, opioids, capsaicin, local anesthetics, and α-adrenoceptor agonists are being used in a variety of clinical states. There also are some clinical data on the use of topical antidepressants and glutamate receptor antagonists. There are preclinical data supporting the potential for development of local formulations of adenosine agonists, cannabinoid agonists, cholinergic ligands, cytokine antagonists, bradykinin antagonists, ATP antagonists, biogenic amine antagonists, neuropeptide antagonists, and agents that alter the availability of nerve growth factor. Given that activation of sensory neurons involves multiple mediators, combinations of agents targeting different mechanisms may be particularly useful. Topical analgesics represent a promising area for future drug development.
Development of wheezing in patients with cough variant asthma during an increase in airway responsiveness
Authors: Y.y Koh, J.h Jeong, Y Park, C.k Kim
Journal: European Respiratory Journal (1999)

Two theories explaining the mechanism for the manifestation of cough without wheeze in patients with cough variant asthma (CVA) are either a higher wheezing threshold or a milder degree of airway hyperresponsiveness. A significant proportion of patients diagnosed as having CVA eventually develop wheezing. The aim of this study was to investigate whether this change in the manifestation of asthma was associated with a decrease in wheezing threshold and/or an increase in airway hyperresponsiveness. Thirty-six children (7-15 yrs) with CVA were prospectively studied for 4 yrs. Bronchial provocation tests with methacholine using the stepwise increasing concentration technique were performed annually to measure the provocative cumulative dose producing a 20% fall in forced expiratory volume in one second (PD20). Wheezing thresholds were additionally determined at the initiation of and the end of the study (development of wheezing, or after 4 yrs). Sixteen (Group 1) of 29 patients available for the follow-up developed clinical wheezing during the period; 13 patients (Group 2) stayed as CVA or their cough resolved. There was no significant change in wheezing thresholds from the initiation to the end of the study (Group 1: 40.9+/-8.2% versus 40.2+/-8.3%; Group 2: 41.4+/-7.1% versus 40.1+/-7.3%). Methacholine PD20 (geometric mean, range of 1 SD), expressed as breath unit (BU), significantly decreased in Group 1 patients as they developed wheezing (initial versus wheezing year: 60.8 BU, 29.2-126.5 versus 32.8 BU, 11.5-93.3; p&lt;0.01), whereas the value did not change in Group 2 patients (initial versus after 4 yrs: 85.3 BU, 45.2-161.1 versus 84.3 BU, 39.7-179.1; NS). The results suggest that an increase in airway hyperresponsiveness, but not a decrease in wheezing threshold, may have a pathogenetic role in the development of wheezing during the course of cough variant asthma in childhood.
Serum immunoglobulin free light chain assessment in rheumatoid arthritis and primary Sjogren's syndrome
Authors: J-E Gottenberg, F Aucouturier, J Goetz, C Sordet, I Jahn, M Busson, J-M Cayuela, J Sibilia, X Mariette
Journal: Annals of the Rheumatic Diseases (2006)

<b>Background:</b> B cell activation may result in an increased secretion of immunoglobulin free light chains (FLCs) in autoimmune diseases. <b>Objective:</b> To analyse serum FLC levels in patients with rheumatoid arthritis and in those with primary Sjögren's syndrome (pSS). <b>Patients and methods:</b> Blood samples were collected from 80 healthy blood donors, 50 patients with rheumatoid arthritis and 139 patients with pSS. Serum FLC level was measured using a new quantitative immunoassay. <b>Results:</b> Mean (standard error (SE)) serum κ and λ FLC levels were significantly higher in patients with rheumatoid arthritis and in those with pSS than in controls (κ : 18.9 (1.1) and 16.3 (1.4) <i>v</i> 10.5 (0.4) mg/l, p&lt;0.001 and p = 0.001, respectively; λ: 16.7 (1.2) and 19.3 (1.5) <i>v</i> 11.6 (0.6) mg/l, p&lt;0.001 for both). 18 (36%) patients with rheumatoid arthritis and 31 (22.3%) patients with pSS had abnormal serum FLC levels (increased κ or λ levels and abnormal ratio of κ:λ). Serum κ and λ levels were correlated with other B cell activation markers in both diseases. FLC levels increased with disease activity, because, unlike total gammaglobulin and immunoglobulin G levels, they were significantly correlated with Disease Activity Score 28 in patients with rheumatoid arthritis (p = 0.004 for κ, p = 0.05 for λ) and with extraglandular involvement in pSS (p = 0.01 for κ, p = 0.04 for λ). <b>Conclusion:</b> FLC levels are increased and correlate with disease activity in patients with rheumatoid arthritis and in those with pSS, two diseases in which increased risk of lymphoma could result from persistent B cell activation and disease activity. Further studies are required to determine whether FLC assessment could represent a relevant biomarker for response to treatment (especially B cell depletion) and for the risk of lymphoma in autoimmune diseases.