tbuckley/cabot-search huggingface dataset:
Chronic kidney disease (CKD) - A forgotten co-morbidity in COPD
Authors: Nawaid Ahamd, Usman Maqsood, Raana Haqqee
Journal: European Respiratory Journal (2012)

Background:

CKD is a less recognized co-morbidity in COPD and its impact on exacerbations and mortality has been under reported.

Objectives:

To look at the prevalence of CKD in patients admitted to hospital with exacerbation of COPD. Secondarily, to compare the length of stay (LOS) in hospital and all cause mortality between the CKD and non-CKD cohort.

Methods:

We included all patients admitted to hospital with a COPD exacerbation¹ from 1st January 2010 to 31st December 2010. CKD was defined as eGFR<60ml/min/sq.m for at least 3 months². Data was analysed by independent sample t-test, chi-square and Mann Whitney U test using online tool Vassar stats and significance reported at p≤0.05.

Results:

161 patients (56% females) were admitted each with FEV1/FVC ratio≤0.7 and median FEV1 36% predicted. Spirometry and BMI data were analysed on 113 patients (CKD n= 90, non-CKD n=23) as records for 48 patients could not be obtained. The prevalence of CKD was 18.6% (n=30). CKD group, was older (mean age 75.8 yrs vs 69.2 yrs; p=0.001), included more males (45 % vs 43%), had higher Body Mass Index (30 vs 23.8 kg/m2; p= 0.002), had better FEV1 (46 vs 35.5 % predicted; p= 0.02) and longer LOS (8 vs 6 days; p= 0.042). There was no significant difference in mortality between the two groups (n= 7 vs n=30; p=0.84).

Conclusion:

CKD is prevalent in COPD and has a significant effect on the LOS during exacerbations; however it does not contribute to increased one year mortality. Hence, more work is required in this field

References:

1. ICD code J44.1

2. National Kidney Foundation Kidney Disease Outcome Quality Initiative Advisory Board.
The SCID-hu Mouse: A Small Animal Model for HIV Infection and Pathogenesis
Authors: J McCune, H Kaneshima, J Krowka, R Namikawa, H Outzen, B Peault, L Rabin, C C Shih, E Yee, M Lieberman
Journal: Annual Review of Immunology (1991)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Increased production of tumour necrosis factor-alpha interleukin-1 beta, and interleukin-6 by morphologically normal intestinal biopsies from patients with Crohn's disease.
Authors: J M Reimund, C Wittersheim, S Dumont, C D Muller, J S Kenney, R Baumann, P Poindron, B Duclos
Journal: Gut (1996)

BACKGROUND: Increasing evidence points to a important role for inflammatory cytokines for the pathogenesis of Crohn9s disease. AIM: To compare the secretion rate of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) by morphologically normal and inflamed intestinal mucosa from patients with Crohn9s disease. RESULTS: Organ cultures of intestinal biopsy specimens taken from areas of affected mucosa from patients with Crohn9s disease spontaneously produced increased amounts of TNF-alpha, IL-1 beta, and IL-6 compared with controls but also biopsy specimens taken in macroscopically and microscopically unaffected areas in the same patients. Concentrations of IL-1 beta and IL-6 measured in the supernatant fluid of biopsy cultures were positively correlated with the degree of tissue involvement measured by both endoscopic and histological grading. By contrast, TNF-alpha concentrations were not correlated to endoscopic and histological grading. CONCLUSIONS: These consistently raised TNF-alpha, IL-1 beta and IL-6 secretions by normal appearing mucosa from patients with Crohn9s disease provide evidence for a sustained immune stimulation in Crohn9s disease even in the absence of patent inflammation. The results shed a new light on the role of inflammatory cytokines in the onset of intestinal tissue damage in Crohn9s disease and suggest that the range of intestinal lesions in Crohn9s disease may be wider than suspected on the basis of regular endoscopic and histological examinations.
Age related, structured educational programmes for the management of atopic dermatitis in children and adolescents: multicentre, randomised controlled trial
Authors: Doris Staab, Thomas L Diepgen, Manigé Fartasch, Jörg Kupfer, Thomas Lob-Corzilius, Johannes Ring, Sibylle Scheewe, Reginald Scheidt, Gerhard Schmid-Ott, Christina Schnopp, Rüdiger Szczepanski, Thomas Werfel, Marita Wittenmeier, Ulrich Wahn, Uwe Gieler
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objective</b> To determine the effects of age related, structured educational programmes on the management of moderate to severe atopic dermatitis in childhood and adolescence. <b>Design</b> Multicentre, randomised controlled trial. <b>Setting</b> Seven hospitals in Germany. <b>Participants</b> Parents of children with atopic dermatitis aged 3 months to 7 years (n = 274) and 8-12 years (n = 102), adolescents with atopic dermatitis aged 13-18 years (n = 70), and controls (n = 244, n = 83, and n = 50, respectively). <b>Interventions</b> Group sessions of standardised intervention programmes for atopic dermatitis once weekly for six weeks or no education (control group). <b>Main outcome measures</b> Severity of eczema (scoring of atopic dermatitis scale), subjective severity (standardised questionnaires), and quality of life for parents of affected children aged less than 13 years, over 12 months. <b>Results</b> Significant improvements in severity of eczema and subjective severity were seen in all intervention groups compared with control groups (total score for severity: age 3 months to 7 years - 17.5, 95% confidence intervals - 19.6 to - 15.3 <i>v</i> - 12.2, - 14.3 to - 10.1; age 8-12 years - 16.0, - 20.0 to - 12.0 <i>v</i> - 7.8, - 11.4; - 4.3; and age 13-18 years - 19.7, - 23.7 to - 15.7 <i>v</i> - 5.2, - 10.5 to 0.1). Parents of affected children aged less than 7 years experienced significantly better improvement in all five quality of life subscales, whereas parents of affected children aged 8-12 years experienced significantly better improvement in three of five quality of life subscales. <b>Conclusion</b> Age related educational programmes for the control of atopic dermatitis in children and adolescents are effective in the long term management of the disease.
RNA Interference Inhibition of Matrix Metalloproteinase-1 Prevents Melanoma Metastasis by Reducing Tumor Collagenase Activity and Angiogenesis
Authors: Jessica S. Blackburn, C. Harker Rhodes, Charles I. Coon, Constance E. Brinckerhoff
Journal: Cancer Research (2007)

Abstract Melanoma incidence is increasing worldwide, and metastatic melanoma is almost completely resistant to every known therapy. New approaches to treating melanoma are urgently needed, and a greater understanding of the biology of melanoma invasion and metastasis will aid in their creation. A high proportion of invasive melanomas have a constitutively active Raf/mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) signaling cascade; however, the downstream effectors of ERK signaling that contribute to melanoma invasion and metastasis are unknown. ERK signaling drives the production of the interstitial collagenase matrix metalloproteinase-1 (MMP-1), which is expressed specifically by invasive melanomas. Using short hairpin RNAs (shRNA) to knock down MMP-1 expression in a human melanoma cell line, we investigated the role of MMP-1 in melanoma metastasis in a xenograft model. Knockdown of MMP-1 had no effect on primary tumor growth, but reduction of MMP-1 expression significantly decreased the ability of the melanoma to metastasize from the orthotopic site in the dermis to the lung. Mechanistically, tumor cells expressing MMP-1 shRNAs had diminished collagenase activity, which is required for tumor cell invasion. Additionally, attenuation of MMP-1 expression reduced angiogenesis. These results show, for the first time, that targeted inhibition of MMP-1, a single effector of the Raf/MEK/ERK signaling cascade, prevents the progression of melanoma from a primary to metastatic tumor and, as such, may represent a useful therapeutic tool in controlling this disease. [Cancer Res 2007;67(22):10849–58]
Dysmotility of the small intestine in irritable bowel syndrome.
Authors: J E Kellow, S F Phillips, L J Miller, A R Zinsmeister
Journal: Gut (1988)

Though the pathophysiology of the irritable bowel syndrome (IBS) is commonly attributed to dysfunction of the large intestine, evidence exists to incriminate the small bowel. In order to further explore the role of the small bowel in IBS several stimuli were applied, in an attempt to unmask the dysmotility of the jejunum and ileum. These included infusions of cholecystokinin-octapeptide (CCK-OP), a high fat meal, neostigmine and balloon distension of the ileum. Three groups (n = 8) each of age and sex matched healthy volunteers were studied; patients with IBS complained of predominant constipation (n = 8) or diarrhoea (n = 8). Patients with IBS responded excessively to stimulation by CCK-OP, fatty meal, and ileal distension. In general patients with diarrhoea were more sensitive to stimuli than those with constipation. The ileum responded more to stimulation than the jejunum. As in the large bowel, stimuli appear to unmask intestinal dysmotility in patients with IBS. Motor abnormalities were often accompanied by abdominal symptoms, raising the possibility that dysfunction of the small bowel contributes to the symptoms of IBS.
STUDIES ON THE OXIDASE PROPERTIES OF CERULOPLASMIN: FACTORS IN NORMAL AND WILSON'S-DISEASE SERUM AFFECTING OXIDASE ACTIVITY
Authors: J. M. Walshe
Journal: Journal of Clinical Investigation (1963)

The oxidase activity of normal serum is due to the presence of the blue copper protein, ceruloplasmin. This is an a-globulin of molecular weight 151,000 containing 8 copper atoms per molecule (1). Its physiological substrate, if any, is unknown (2), but it has a weak oxidase activity for compounds that can be oxidized to quinone or quinone imines (3). The copper atoms in the protein appear to be arranged in functional pairs, and it seems probable that a specific function exists that will be shown to depend upon the unique chemical nature of the protein, as has already been demonstrated for another copper protein, tyrosinase (4). The concentration of ceruloplasmin in serum can be measured by estimating light absorption at 605 mp, before and after the destruction of the copper-protein bond with cyanide, by immunochemical techniques, or by measuring the oxidation of paraphenylene diamine (or related compounds) either in a Warburg flask or a spectrophotometer (4). These three methods all give comparable results, although measuring different properties of the protein: the copper-protein bond, the antigenic site, and the catalytic center. The
Oseltamivir Resistance during Treatment of Influenza A (H5N1) Infection
Authors: Menno D. de Jong, Tran Tan Thanh, Truong Huu Khanh, Vo Minh Hien, Gavin J.D. Smith, Nguyen Vinh Chau, Bach Van Cam, Phan Tu Qui, Do Quang Ha, Yi Guan, J.S. Malik Peiris, Tran Tinh Hien, Jeremy Farrar
Journal: New England Journal of Medicine (2005)

Influenza A (H5N1) virus with an amino acid substitution in neuraminidase conferring high-level resistance to oseltamivir was isolated from two of eight Vietnamese patients during oseltamivir treatment. Both patients died of influenza A (H5N1) virus infection, despite early initiation of treatment in one patient. Surviving patients had rapid declines in the viral load to undetectable levels during treatment. These observations suggest that resistance can emerge during the currently recommended regimen of oseltamivir therapy and may be associated with clinical deterioration and that the strategy for the treatment of influenza A (H5N1) virus infection should include additional antiviral agents.
Protruding Atheromas in the Thoracic Aorta and Systemic Embolization
Authors: P A Tunick, J L Perez, I Kronzon
Journal: Annals of Internal Medicine (1991)

To determine whether protruding atheromas in the thoracic aorta are a risk factor for systemic embolization.Case-control study.A referral hospital.A total of 122 patients with a history of stroke, transient ischemic attack, or peripheral emboli and an equal number of age- and sex-matched control patients.Evaluation using transesophageal echocardiography was done in case patients to detect protruding atheromas in the thoracic aorta and in control patients for cardiac indications other than emboli.Matched logistic regression showed that the presence of protruding atheromas was strongly related to the occurrence of embolic symptoms (odds ratio, 3.2; 95% Cl, 1.6 to 6.5; P less than 0.001). Furthermore, atheromas with mobile components were present only in case patients. When known risk factors for stroke (hypertension and diabetes) were added to the model, the presence of protruding atheromas remained an independent risk factor for embolic symptoms (odds ratio, 3.8). Hypertension was also independently associated with embolic symptoms (odds ratio, 2.7), but diabetes was not (odds ratio, 1.0).Protruding atheromas in the thoracic aorta can be detected by transesophageal echocardiography and should be considered as a cause of strokes, transient ischemic attacks, and peripheral emboli.
Exercise training in children with asthma: a systematic review
Authors: Vera HM Wanrooij, Maartje Willeboordse, Edward Dompeling, Kim DG van de Kant
Journal: British Journal of Sports Medicine (2013)

Exercise can provoke asthma symptoms, such as dyspnoea, in children with asthma. Exercise-induced bronchoconstriction (EIB) is prevalent in 40–90% of children with asthma. Conversely, exercise can improve physical fitness. The purpose of this paper is to provide a systematic review of the literature regarding the effects of exercise training in children with asthma, particularly in relation to: EIB, asthma control, pulmonary function, cardiorespiratory parameters and parameters of underlying pathophysiology. A systematic search in several databases was performed. Controlled trials that undertook a physical training programme in children with asthma (aged 6–18 years) were selected. Twenty-nine studies were included. Training had positive effects on several cardiorespiratory fitness parameters. A few studies demonstrated that training could improve EIB, especially in cases where there was sufficient room for improvement. Peak expiratory flow was the only lung function parameter that could be improved substantially by training. The effects of training on asthma control, airway inflammation and bronchial hyper-responsiveness were barely studied. Owing to the overall beneficial effects of training and the lack of negative effects, it can be concluded that physical exercise is safe and can be recommended in children with asthma. A training programme should have a minimum duration of 3 months, with at least two 60 min training sessions per week, and a training intensity set at the (personalised) ventilatory threshold. Further research is recommended regarding the effects of exercise on underlying pathophysiological mechanisms and asthma control in children with asthma.
Ten principles for clean air
Authors: B. Brunekreef, I. Annesi-Maesano, J.G. Ayres, F. Forastiere, B. Forsberg, N. Künzli, J. Pekkanen, T. Sigsgaard
Journal: European Respiratory Journal (2012)

The European “Year of the Air” 2013 will be upon us soon: over the next several months, the European Union (EU) will revise its main air pollution control policies. Lack of clean air is one of the most important environmental threats to public health in Europe today. The European Respiratory Society Environment and Health Committee (www.ersnet.org) has developed 10 concise principles for clean air, which summarise the scientific state of the art and provide guidance for public health policy. This editorial was written in order to explain these 10 principles.

1) Citizens are entitled to clean air, just like clean water and safe food .

This principle, really, should be self-evident to the extent that one should be embarrassed to even mention it. But the reality is that millions of Europeans live in areas where it is unsafe to breathe the air around them.

The most recent EU key directive on ambient air quality is Directive 2008/50/EC. It recognises the need to reduce pollution to levels which minimise harmful effects on human health. The limit values adopted for airborne particulate matter were, however, far higher than recommended by the World Health Organization (WHO). For example, an annual average limit value for respirable particles (particulate matter with a 50% cut-off aerodynamic diameter of 2.5 μm; PM2.5) was set at 25 μg·m−3 which is 2.5 times higher than the level recommended by the WHO. WHO guidelines are based on health considerations only, and do not take into account the economical or technical feasibility of meeting the guidelines. The EU Directive recognises that there is no identifiable threshold for PM2.5 and states that policies should aim at general reductions in concentrations at urban background sites. However, no binding legislative measures have been taken so far to enforce this. A detailed …
Current state and future directions of autologous hematopoietic stem cell transplantation in systemic lupus erythematosus
Authors: Gabor G Illei, Ricard Cervera, Richard K Burt, Andrea Doria, Falk Hiepe, David Jayne, Steven Pavletic, Thierry Martin, Alberto Marmont, Riccardo Saccardi, Alexandre E Voskuyl, Dominique Farge
Journal: Annals of the Rheumatic Diseases (2011)

Autologous haematopoietic stem cell transplantation (AHSCT) has been proposed as a treatment modality which may arrest the autoimmune disease process and lead to sustained treatment-free remissions. Since the first consensus statement in 1997, approximately 200 autologous bone marrow or haematopoietic stem cell transplantations (HSCTs) have been reported worldwide for systemic lupus erythematosus (SLE). The current state of AHSCT in SLE was reviewed at a recent meeting of the autoimmune working party of the European Group for Blood and Marrow Transplantation. There was general agreement among experts in this field that in patients with severe SLE refractory to conventional immunosuppressive treatments, AHSCT can achieve sustained clinical remissions (ranging from 50% to 70% disease-free survival at 5 years) associated with qualitative immunological changes not seen with other forms of treatment. However, this clinical benefit is associated with an increase in short-term mortality in most studies. Improving patient selection, long-term follow-up of patients after AHSCT, optimisation of induction and maintenance treatment together with detailed analysis of the immune system are identified as key areas for future research. Optimally, AHSCT should be compared with conventional treatment in randomised controlled trials. Development of stronger transplant registries, defining a core set of clinical data and standardising biological sample collections would make future collaborations and comparison of studies more feasible.
A Pooled Analysis of Vitamin D Dose Requirements for Fracture Prevention
Authors: Heike A. Bischoff-Ferrari, Walter C. Willett, Endel J. Orav, Paul Lips, Pierre J. Meunier, Ronan A. Lyons, Leon Flicker, John Wark, Rebecca D. Jackson, Jane A. Cauley, Haakon E. Meyer, Michael Pfeifer, Kerrie M. Sanders, Hannes B. Stähelin, Robert Theiler, Bess Dawson-Hughes
Journal: New England Journal of Medicine (2012)

The results of meta-analyses examining the relationship between vitamin D supplementation and fracture reduction have been inconsistent.We pooled participant-level data from 11 double-blind, randomized, controlled trials of oral vitamin D supplementation (daily, weekly, or every 4 months), with or without calcium, as compared with placebo or calcium alone in persons 65 years of age or older. Primary end points were the incidence of hip and any nonvertebral fractures according to Cox regression analyses, with adjustment for age group, sex, type of dwelling, and study. Our primary aim was to compare data from quartiles of actual intake of vitamin D (including each individual participant's adherence to the treatment and supplement use outside the study protocol) in the treatment groups of all trials with data from the control groups.We included 31,022 persons (mean age, 76 years; 91% women) with 1111 incident hip fractures and 3770 nonvertebral fractures. Participants who were randomly assigned to receive vitamin D, as compared with those assigned to control groups, had a nonsignificant 10% reduction in the risk of hip fracture (hazard ratio, 0.90; 95% confidence interval [CI], 0.80 to 1.01) and a 7% reduction in the risk of nonvertebral fracture (hazard ratio, 0.93; 95% CI, 0.87 to 0.99). By quartiles of actual intake, reduction in the risk of fracture was shown only at the highest intake level (median, 800 IU daily; range, 792 to 2000), with a 30% reduction in the risk of hip fracture (hazard ratio, 0.70; 95% CI, 0.58 to 0.86) and a 14% reduction in the risk of any nonvertebral fracture (hazard ratio, 0.86; 95% CI, 0.76 to 0.96). Benefits at the highest level of vitamin D intake were fairly consistent across subgroups defined by age group, type of dwelling, baseline 25-hydroxyvitamin D level, and additional calcium intake.High-dose vitamin D supplementation (≥800 IU daily) was somewhat favorable in the prevention of hip fracture and any nonvertebral fracture in persons 65 years of age or older. (Funded by the Swiss National Foundations and others.).
Effect of antioxidants, resveratrol, quercetin, andN-acetylcysteine, on the functions of cultured rat hepatic stellate cells and kupffer cells
Authors: Norifumi Kawada, Shuichi Seki, Masayasu Inoue, Tetsuo Kuroki
Journal: Hepatology (1998)

Effects of antioxidants, resveratrol, quercetin, and N -acetylcysteine (NAC) on the functions of cultured rat hepatic stellate cells and Kupffer cells were studied. These compounds dose-dependently suppressed serum-dependent proliferation of stellate cells as determined by [ 3 H]thymidine and 5-bromo-2′-deoxyuridine uptake. Expression of smooth muscle α-actin was suppressed by a high dose of resveratrol and quercetin. These phenolic compounds also suppressed inositol phosphate metabolism, tyrosine phosphorylation, and mitogen-activated protein (MAP) kinase activation in platelet-derived growth factor/BB-stimulated stellate cells. Moreover, the phenolic compounds selectively reduced the level of cell cycle protein cyclin D1 in stellate cells. Thus, resveratrol and quercetin might inhibit stellate cell activation by perturbing signal transduction pathway and cell cycle protein expression, whereas mechanism of potent antiproliferative effect of NAC remains to be elucidated. On the other hand, kinetic analysis showed that production of nitric oxide (NO) and tumor necrosis factor α (TNF-α) by lipopolysaccharide-stimulated Kupffer cells was strongly inhibited by resveratrol and quercetin but not by NAC. Although expression of messenger RNAs for inducible NO synthase and TNF-α was not affected by the phenolic compounds, cellular levels of inducible NO synthase and TNF-α secretion were suppressed significantly, indicating the posttranscriptional process of generating these proteins might be affected predominantly by these phenolic compounds. Thus, NAC and these phenolic compounds may have therapeutic potential against liver injury by regulating functions of hepatic stellate cells and Kupffer cells.