tbuckley/cabot-search huggingface dataset:
Cystic fibrosis: to ion transport and beyond
Authors: A. Bush, J. Davies
Journal: European Respiratory Journal (2010)

<h3>Background</h3> Bronchiolitis is the most common reason for hospital admission in infants. High-flow oxygen therapy has emerged as a new treatment; however, the cost-effectiveness of using it as first-line therapy is unknown. <h3>Objective</h3> To compare the cost of providing high-flow therapy as a first-line therapy compared with rescue therapy after failure of standard oxygen in the management of bronchiolitis. <h3>Methods</h3> A within-trial economic evaluation from the health service perspective using data from a multicentre randomised controlled trial for hypoxic infants (≤12 months) admitted to hospital with bronchiolitis in Australia and New Zealand. Intervention costs, length of hospital and intensive care stay and associated costs were compared for infants who received first-line treatment with high-flow therapy (early high-flow, n=739) or for infants who received standard oxygen and optional rescue high-flow (rescue high-flow, n=733). Costs were applied using Australian costing sources and are reported in 2016–2017 AU$. <h3>Results</h3> The incremental cost to avoid one treatment failure was AU$1778 (95% credible interval (CrI) 207 to 7096). Mean cost of bronchiolitis treatment including intervention costs and costs associated with length of stay was AU$420 (95% CrI −176 to 1002) higher per infant in the early high-flow group compared with the rescue high-flow group. There was an 8% (95% CrI 7.5 to 8.6) likelihood of the early high-flow oxygen therapy being cost saving. <h3>Conclusions</h3> The use of high-flow oxygen as initial therapy for respiratory failure in infants with bronchiolitis is unlikely to be cost saving to the health system, compared with standard oxygen therapy with rescue high-flow.
Diagnosis and Prevention of Bovine Spongiform Encephalopathy and Variant Creutzfeldt-Jakob Disease
Authors: David N. Irani, Richard T. Johnson
Journal: Annual Review of Medicine (2003)

An outbreak of bovine spongiform encephalopathy (BSE) arose in the United Kingdom as a result of prions entering and being recycled through the ruminant food chain. Humans have since developed a variant form of Creutzfeldt-Jakob disease (vCJD), also mostly in the United Kingdom, that occurs in younger individuals and causes prominent psychiatric and/or behavioral manifestations early in disease. Laboratory studies now provide strong evidence that the causative agent of BSE in cattle and vCJD in humans share a common origin. Because of a lack of information regarding the incubation period of vCJD and the number of people who may have been exposed, the future scope of this disease remains unknown. Control of the current and any future outbreaks in cattle requires strict measures to prevent contamination of the animal food chain with prions of any species. Prevention of human exposure mandates the avoidance of neural tissue in all human foods.
Outcome in preschool age after hospitalization for wheeze in infancy
Authors: Nele Sigurs, Christina Kavouridou, Per Gustafsson
Journal: European Respiratory Journal (2012)

Background Risk factors for the progression from early infant wheeze to the development of later bronchial obstructive symptoms are not fully known.

Aim To investigate if the development of bronchial obstructive symptoms during preschool years was influenced by time of the first hospitalization in infancy for acute respiratory distress with wheeze.

Subjects 150 infants younger than 18 months were hospitalized for the first time at Boras hospital with the diagnoses acute bronchitis, bronchiolitis or asthma during one calendar year. For 110 infants it was the first episode ever. 144 children (85 males) were followed up (96%), ages: < 6 months, 67 infants, 6-<12 months, 57 infants, and 12-<18 months, 20 infants.

Methods All hospital records were analysed. Structured telephone interviews were made with the families of the 144 children, at mean age 4.5 years (range 3.5 – 5.6 years). Data from medical records of all the children with reported remaining respiratory symptoms were analysed.

Results 71 children (49%) still had current wheeze requiring medication periodically (60 children) or continuously (11 children). Episodic (viral) wheeze was reported in 46 and multiple-trigger wheeze in 25 individual with a similar distribution in the three age groups (21/67, 21/57, 4/20 and 11/67, 9/57, 5/20 respectively). Suspected or diagnosed allergy to inhaled allergens was reported in 15 of the 71 symptomatic children (21%) and in one child without wheeze.

Conclusions Almost half of infants with hospitalization due to early wheeze had current wheezing symptoms, needing medication at mean age 4.5 years. In this heterogeneous group of children age at the first hospitalization did not seem to influence the outcome.
Fertilisation authority rules in favour of embryo selection for tissue donation
Authors: Rebecca Coombes
Journal: BMJ (2004)

The UK Human Fertilisation and Embryology Authority has given parents new powers to select embryos so that the baby created can become a tissue donor to an ill sibling.

The move relaxes regulations laid down by the authority in 2001 to govern preimplantation genetic diagnosis—rules that were widely criticised as inconsistent.

Before last week's decision tissue typing could be carried out only in cells that had already been taken from embryos for the purpose of testing for inherited diseases. The process was considered too invasive to be used more widely.

But Suzi Leather, the authority's …
Tumour necrosis factor independent disease mechanisms in rheumatoid arthritis: a histopathological study on the effect of infliximab on rheumatoid nodules
Authors: D Baeten
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> It has been suggested that the immunopathology of rheumatoid nodules parallels that of inflamed synovium in rheumatoid arthritis (RA). <b>Objective:</b> To analyse the effect of infliximab on the immunopathology of rheumatoid nodules in order to provide new insights into the relationship between synovial inflammation and rheumatoid nodules. <b>Materials and methods:</b> Nodules were present at baseline in six patients with RA and after infliximab treatment in five patients, including paired nodules before and after treatment in three patients. In one patient, the nodule appeared during treatment. Paraffin sections were used for histological analysis. Frozen sections were stained by immunohistochemistry for cellular markers (CD3, CD4, CD8, CD16, CD20, CD68), blood vessels (CD146, vWF, αvβ3), and adhesion molecules (E-selectin, VCAM-1, ICAM-1). <b>Results:</b> No manifest immunopathological differences were found between the nodules before and after infliximab treatment. All nodules depicted the classical structure with a central necrotic zone, surrounding the palisade layer, and an outer connective tissue zone. Immunohistochemistry showed the presence of CD68+ and CD16+ macrophages in the palisade and the connective tissue zone, as well as a small number of CD3+, CD4+ T lymphocytes in the perivascular areas. Small vessels were seen in the connective tissue and were sometimes positive for the neovascularisation marker αvβ3. They expressed no VCAM-1, E-selectin weakly, but ICAM-1 strongly. ICAM-1 was also strongly expressed on palisade cells. <b>Conclusions:</b> Despite an improvement of articular symptoms, infliximab treatment had no distinct effect on the histopathology of rheumatoid nodules, suggesting that different pathogenetic mechanisms mediate the two disease manifestations in RA.
Effects of calcium and its antagonists on the canine mesenteric circulation.
Authors: K M Walus, J D Fondacaro, E D Jacobson
Journal: Circulation Research (1981)

We studied circulatory and metabolic responses of the intestinal circulation to intraarterial infusions of solutions containing calcium chloride or calcium antagonists in anesthetized dogs. Measurements included blood flow to the terminal ileum, arteriovenous oxygen content difference, distribution of radiolabeled microspheres to the mucosal-submucosal compartment and intraluminal pressure. Calculated parameters included oxygen consumption and fractional mucosal-submucosal blood flow. Both calcium antagonists, nifedipine and diltiazem, increased intestinal blood flow, mainly to the mucosa-submucosa, depressed intestinal motility, and did not change oxygen consumption. Thus, both agents appear to act mainly on resistance vessels without increasing the nutrient circulation. Calcium chloride (1.0-500.0 microgram/kg per min) had a mild constrictor effect; at a dose of 1000.0 microgram/kg per min, calcium chloride became a dilator agent in the mesenteric circulation. The dilator effect of the highest dose of calcium was reversed by digoxin, suggesting the involvement of Na+,K+-ATPase. Nifedipine completely blocked calcium-induced constriction of the intestinal circulation and partly inhibited norepinephrine-induced constriction. Studies on isolated mesenteric arterial smooth muscle revealed that nifedipine relaxed KCl-contracted strips in the presence of external calcium and relaxed norepinephrine-contracted strips in both the presence and absence of external calcium. These in vitro findings suggest that calcium antagonists interfere with the release of calcium from intracellular sites as well as with the slow inward current of calcium.
P221 Temporal Trends in Severity and In-Hospital Mortality in Acute Hypercapnic Respiratory Failure (AHRF) at a Respiratory Ward-Based Non-Invasive Ventilation (NIV) Unit
Authors: H Lewis, C Wharton, S Agarwal, B Beauchamp, B Chakraborty, D Banerjee, AM Turner, R Mukherjee
Journal: Thorax (2012)

<h3>Introduction</h3> Use of NIV for AHRF in COPD, obesity related morbidity, chest wall and neuro muscular conditions have increased significantly over the past decade – there has been a documented 462%increase in acute NIV use in COPD (Chandra D et al. AJRCCM 2011) over 11 years in the United States with similar changes noted in smaller surveys in the UK. In the UK, this has led to the movement of NIV service provision out of critical care at ward-based NIV units. We felt it necessary to analyse temporal trends in the severity and outcomes of ward-based NIV practises. <h3>Methods</h3> Comparison of the in-house NIV registry data 01/08/2004 –31/01/2006 (Period 1) with 01/01/2011 – 30/06/2012(Period 2) at an 11-bedded ward-based NIV unit within a 1000-bedded hospital Trust in central England, looking at mortality, length(duration) of NIV and initial arterial blood pH, the latter being widely accepted as a marker of AHRF severity. <h3>Results</h3> There were 281 episodes of AHRF treated in Period 1 and 240 in Period 2 with similar distribution of gender (non-significant increase in the number of women); acute exacerbations of COPD constituted similar proportion (about 70%)of dominant diagnosis behind AHRF in both periods (associated risk factor documentation, e.g. kyphoscoliosis not analysed); the initial arterial blood pH was significantly lower (median initial pH 7.280 vs 7.261; Wilcoxonrank sum test: p=0.03134; pH significantly lower in Period 2); the mean length (duration) of NIV was significantly higher (median length of NIV 4.0 days vs 6.0 days; Wilcoxon rank sum test: p=0.0000018; Length of NIV is significantly higher in period 2), whilst in-hospital mortality was similar (21.6% vs. 22.7%). <h3>Discussion</h3> Our data confirm the clinical surmise that over time, our ward-based NIV unit is treating more severely ill patients with AHRF who are spending longer periods under acute NIV with no significant change in mortality. Further analysis of population characteristics, co-morbid risk factors for respiratory failure and Domiciliary NIV/Home Mechanical Ventilation practises as well as national trends in NIV use are needed to inform health policy/strategies to deal with long term respiratory conditions.
A7: Initial Assessment of Multi-biomarker Disease Activity Assay in JIA
Authors: Sarah Ringold, Lucy Lu, Carol A. Wallace, Eric H. Sasso, P. Scott Eastman
Journal: Arthritis & Rheumatology (2014)

Background/Purpose:

Current measures of disease activity in JIA, including physician global assessment of disease activity and active joint count, are subjective and potentially confounded by disease heterogeneity and comorbid conditions. A multi-biomarker disease activity assay (MBDA) incorporating a panel of biomarkers may provide objective and quantitative data regarding disease activity that would be of great value to physicians caring for children with JIA. The objective of this investigation was to measure the feasibility of a MBDA developed for RA (Vectra DA, Crescendo Bioscience, Inc), and its individual biomarker components as a measure of disease activity in patients with JIA.



Methods:

Samples were analyzed from a prior cross-sectional, observational study that included 31 children with rheumatoid factor (RF) positive polyarticular JIA (n = 4), RF negative polyarticular JIA (n = 18), or extended oligoarticular JIA (n = 8). All children had established disease and were on treatment (mean disease duration 5 years; range 0–15 years). The Juvenile Arthritis Disease Activity Score (JADAS) based on 10 joints was calculated for each sample and each sample was classified as clinically inactive disease or active disease using the ACR provisional criteria for clinically inactive disease (CID). Samples were analyzed for 18 individual biomarkers, 12 of which comprise Vectra DA and a total Vectra DA score was calculated. Biomarker assays were also performed for a cohort of 44 healthy 18 year-old controls obtained from the ProMeDx specimen bank.



Results:

The mean JADAS value for the cohort was 4.9 (range 0–16.3). The mean Vectra DA score for the healthy controls was 14 (maximum possible score is 100). The mean score was 20 for the children with CID, and 27 for children with active disease. The correlation between the Vectra DA and JADAS was moderate (r = 0.68; Figure 1). The individual biomarker profiles for the control cohort and the children who met criteria for inactive disease appeared similar, but several individual biomarkers, including SAA, CRP, IL-6 and MMP-3 were elevated in the active disease group as compared to the children with CID and controls (Figure 2). 



Conclusion:

These data support the feasibility of the development of a JIA-specific MBDA that will reflect the underlying heterogeneity of the disease process and provide physicians with an objective measure of disease activity. Additional analyses of larger sets of biomarkers using samples with a broad range of disease activities will inform the next steps of assay development.
Stem Cells and the Regeneration of the Aging Cardiovascular System
Authors: Victoria L.T. Ballard, Jay M. Edelberg
Journal: Circulation Research (2007)

It is well established that cardiovascular repair mechanisms become progressively impaired with age and that advanced age is itself a significant risk factor for cardiovascular disease. Although therapeutic developments have improved the prognosis for those with cardiovascular disease, mortality rates have nevertheless remained virtually unchanged in the last twenty years. Clearly, there is a need for alternative strategies for the treatment of cardiovascular disease. In recent years, the idea that the heart is capable of regeneration has raised the possibility that cell-based therapies may provide such an alternative to conventional treatments. Cells that have the potential to generate cardiomyocytes and vascular cells have been identified in both the adult heart and peripheral tissues, and in vivo experiments suggest that these cardiovascular stem cells and cardiovascular progenitor cells, including endothelial progenitor cells, are capable of replacing damaged myocardium and vascular tissues. Despite these findings, the endogenous actions of cardiovascular stem cells and cardiovascular progenitor cells appear to be insufficient to protect against cardiovascular disease in older individuals. Because recent evidence suggests that cardiovascular stem cells and cardiovascular progenitor cells are subject to age-associated changes that impair their function, these changes may contribute to the dysregulation of endogenous cardiovascular repair mechanisms in the aging heart and vasculature. Here we present the evidence for the impact of aging on cardiovascular stem cell/cardiovascular progenitor cell function and its potential importance in the increased severity of cardiovascular pathophysiology observed in the geriatric population.
Bone Marrow Monocyte Lineage Cells Adhere on Injured Endothelium in a Monocyte Chemoattractant Protein-1–Dependent Manner and Accelerate Reendothelialization as Endothelial Progenitor Cells
Authors: Soichiro Fujiyama, Katsuya Amano, Kazutaka Uehira, Masayuki Yoshida, Yasunobu Nishiwaki, Yoshihisa Nozawa, Denan Jin, Shinji Takai, Mizuo Miyazaki, Kensuke Egashira, Takayuki Imada, Toshiji Iwasaka, Hiroaki Matsubara
Journal: Circulation Research (2003)

Peripheral blood (PB)-derived CD14 + monocytes were shown to transdifferentiate into endothelial cell (EC) lineage cells and contribute to neovascularization. We investigated whether bone marrow (BM)- or PB-derived CD34 − /CD14 + cells are involved in reendothelialization after carotid balloon injury. Although neither hematopoietic nor mesenchymal stem cells were included in human BM-derived CD34 − /CD14 + monocyte lineage cells (BM-MLCs), they expressed EC-specific markers (Tie2, CD31, VE-cadherin, and endoglin) to an extent identical to mature ECs. When BM-MLCs were cultured with vascular endothelial growth factors, hematopoietic markers were drastically decreased and new EC-specific markers (Flk and CD34) were induced. BM-MLCs were intra-arterially transplanted into balloon-injured arteries of athymic nude rats. When BM-MLCs were activated by monocyte chemoattractant protein-1 (MCP-1) in vivo or in vitro, they adhered onto injured endothelium, differentiated into EC-like cells by losing hematopoietic markers, and inhibited neointimal hyperplasia. Ability to prevent neointimal hyperplasia was more efficient than that of BM-derived CD34 + cells. MCP-dependent adhesion was not observed in PB-derived CD34 − /CD14 + monocytes. Regenerated endothelium exhibited a cobblestone appearance, blocked extravasation of dye, and induced NO-dependent vasorelaxation. Basal adhesive activities on HUVECs under laminar flow and β 1 -integrin expression (basal and active forms) were significantly increased in BM-MLCs compared with PB-derived monocytes. MCP-1 markedly enhanced adhesive activity of BM-MLCs (2.8-fold) on HUVECs by activating β 1 -integrin conformation. Thus, BM-MLCs can function as EC progenitors that are more potent than CD34 + cells and acquire the ability to adhere on injured endothelium in a MCP-1–dependent manner, leading to reendothelialization associated with inhibition of intimal hyperplasia. This will open a novel window to MCP-1–mediated biological actions and vascular regeneration strategies by cell therapy.
High environmental tobacco smoke and other air pollutants exposure in patients with allergic rhinitis non smokers
Authors: Dragica Pesut, Ljudmila Nagorni-Obradovic, Biljana Savic, Jasmina Maric-Zivkovic, Sanja Radovanovic, Aleksandra Peric-Popadic
Journal: European Respiratory Journal (2012)

Background: Chronic exposure to cigarette smoke inhibits surface immunoglobulin-mediated responses in B cells. Immunomodulatory effects of cigarette smoke are evidence based and the effects of environmental tobacco smoke (ETS) on immune system are in focus of current research.  Aim of the study is to analyse tobacco smoking status in patients (Pts) with allergic rhinitis (AR) with special regard to ETS.  Methods: In this observational questionnaire based study successive series of Pts treated for AR at two tertiary level health care facilities in Belgrade, Serbia, was enrolled from January 2010 to Decembre 2011, and valid questionnaires were analyzed for Pts9 demographic and social data, and tobacco smoking status.  Results Study group consisted of 182 Pts average age: 36.22±12.50; male/female ratio: 0.75. Tobacco smoking status analysis showed: 12.6% current smokers, 15.4% former smokers, and 136/184 (72%) Pts non smokers. About two thirds of the 9non smokers9 have been exposed to ETS while 166/182 (91.2%) Pts have been exposed to both tobacco smoke ingredients (at home and/or at working place), and to the other air pollution.  Conclusion: High proportion of AR Pts is exposed to tobacco smoke and/or the other environmental pollution, which might present a serious problem and challenge for further research in the field of immunomodulation.
Random mutagenesis of two complementarity determining region amino acids yields an unexpectedly high frequency of antibodies with increased affinity for both cognate antigen and autoantigen.
Authors: L P Casson, T Manser
Journal: The Journal of Experimental Medicine (1995)

To gain insight into the mechanism and limitations of antibody affinity maturation leading to memory B cell formation, we generated a phage display library of random mutants at heavy chain variable (V) complementarity determining region 2 positions 58 and 59 of an anti-p-azophenylarsonate (Ars) Fab. Single amino acid substitutions at these positions resulting from somatic hypermutation are recurrent products of affinity maturation in vivo. Most of the ex vivo mutants retained specificity for Ars. Among the many mutants displaying high Ars-binding activity, only one contained a position 58 and 59 amino acid combination that has been previously observed among the monoclonal antibodies (mAbs) derived from Ars-immunized mice. Affinity measurements on 14 of the ex vivo mutants with high Ars-binding activity showed that 11 had higher intrinsic affinities for Ars that the wild-type V region. However, nine of these Fabs also bound strongly to denatured DNA, a property neither displayed by the wild-type V region nor observed among the mutants characteristic of in vivo affinity maturation. These data suggest that ex vivo enhancement of mAb affinity via site-directed and random mutagenesis approaches may often lead to a reduction in antibody specificity that could complicate the use of the resulting mAbs for diagnostic and therapeutic applications. Moreover, the data are compatible with a hypothesis proposing that increased specificity for antigen, rather than affinity per se, is the driving force for formation of the memory B cell compartment.
Conservation Within Artiodactyls of an AATA Interrupt in the IGF-I Microsatellite for 19–35 Million Years
Authors: M Reza Shariflou, C Moran
Journal: Molecular Biology and Evolution (2000)

Occurrence of an AATA interrupt in the IGF-I microsatellite was investigated in a number of Artiodactyl species, namely pigs, camels, deer, cattle, goats, and sheep. Comparison of DNA sequences in the 5' flank of the microsatellite in these species revealed that the interrupt within the microsatellite is conserved in deer, cattle, sheep, and goats but is absent from camels and pigs. The interrupt was introduced into the Artiodactyl phylogeny after the divergence of the Camelidae but before the divergence of the Cervidae, and thus its time of origin can be estimated to be 19-35 MYA. In contrast to the repeat units which are hypermutable, the interrupt has been conserved for a very long time and may even have suppressed microsatellite variation by inhibiting replication slippage. A 12-bp deletion in the 5' flank of the microsatellite in camels corresponds to a consensus reversed repeat in deer, cattle, sheep, and goats with unknown functional significance. Apart from this deletion, the 5' flank of the microsatellite is highly conserved in Artiodactyl species.