tbuckley/cabot-search huggingface dataset:
PRINTO/PRES international website for families of children with rheumatic diseases: www.pediatric-rheumatology.printo.it
Authors: N Ruperto
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To prepare a website for families and health professionals containing up to date information about paediatric rheumatic diseases (PRD). <b>Methods:</b> Firstly, paediatric rheumatology centres and family self help associations were surveyed to characterise current clinical practice of physicians providing care for children with PRD, research activities, and training facilities of each centre. Secondly, international consensus was reached on the content of the website. Finally, the website was developed and the texts translated. <b>Results:</b> The web page contains three main sections: (<i>a</i>) description for families of the characteristics of 15 PRD; (<i>b</i>) list of paediatric rheumatology centres; (<i>c</i>) contact information for family self help associations. A version for 45 countries in 52 languages (with another three in progress) is now available on the web. 291 surveys from 171 centres and 102 family associations were received from 42 countries. The median proportion of time spent in paediatric practice in the centres examined was 100%, with 70% of this time dedicated to paediatric rheumatology. 90% of the centres were willing to perform clinical trials in the future. <b>Conclusions:</b> The PRINTO/PRES website provides a well defined and competent set of information about PRD, with appropriate multiple translated versions and easy web navigational direction.
Non- cystic fibrosis bronchiectasis in primary antibody deficiency patients
Authors: Marina Karakina, Irina Tuzankina, Yugeniy Beltukov, Helena Vlasova
Journal: European Respiratory Journal (2014)

Our local register of patients with primary immunodeficiencies includes 162 cases with confirmed antibody deficiency. Among them there are 95 children with median age of 8.7 years and 67 adults with median age of 28.6 years. The register covers the population of Sverdlovsk region of Russian population with 4.8 mln inhabitants. Non-cystic fibrosis bronchiectasis was diagnosed in 20 out of 162 patients (12.3%). Non-cystic fibrosis bronchiectasis was detected more frequently in patients with agammaglobulinemia (in 12 out of 14 cases, 85.7%) and common variable immunodeficiency (in 8 out of 20 cases, 34.8%) in comparison to selective IgA deficiency (none out of 124 cases) (p
Allogeneic haematopoietic stem cell transplantation for metastatic renal carcinoma in Europe
Authors: L. Barkholt, M. Bregni, M. Remberger, D. Blaise, J. Peccatori, G. Massenkeil, P. Pedrazzoli, A. Zambelli, J.-O. Bay, S. Francois, R. Martino, C. Bengala, M. Brune, S. Lenhoff, A. Porcellini, M. Falda, S. Siena, T. Demirer, D. Niederwieser, O. Ringdén
Journal: Annals of Oncology (2006)
Incidence of Dementia With Lewy Bodies and Parkinson Disease Dementia
Authors: Rodolfo Savica, Brandon R. Grossardt, James H. Bower, Bradley F. Boeve, J. Eric Ahlskog, Walter A. Rocca
Journal: JAMA Neurology (2013)

Epidemiologic data on dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD) remain limited in the United States and worldwide. These data are essential to guide research and clinical or public health interventions.To investigate the incidence of DLB among residents of Olmsted County, Minnesota, and compare it with the incidence of PDD.The medical records linkage system of the Rochester Epidemiology Project was used to identify all persons who developed parkinsonism and, in particular, DLB or PDD from 1991 through 2005 (15 years). A movement disorders specialist reviewed the complete medical records of each suspected patient to confirm the diagnosis.Olmsted County, Minnesota, from 1991 through 2005 (15 years).All the residents of Olmsted County, Minnesota, who gave authorization for medical record research.Incidence of DLB and PDD.Among 542 incident cases of parkinsonism, 64 had DLB and 46 had PDD. The incidence rate of DLB was 3.5 per 100,000 person-years overall, and it increased steeply with age. The incidence of PDD was 2.5 overall and also increased steeply with age. The incidence rate of DLB and PDD combined was 5.9. Patients with DLB were younger at onset of symptoms than patients with PDD and had more hallucinations and cognitive fluctuations. Men had a higher incidence of DLB than women across the age spectrum. The pathology was consistent with the clinical diagnosis in 24 of 31 patients (77.4%) who underwent autopsy.The overall incidence rate of DLB is lower than the rate of Parkinson disease. The incidence of DLB increases steeply with age and is markedly higher in men. This men to women difference may suggest different etiologic mechanisms. Our findings may guide health care planning and prompt new studies.
IL-4– and IL-5–positive T lymphocytes, eosinophils, and mast cells in allergen-induced late-phase cutaneous reactions in atopic subjects☆☆☆★★★
Authors: Luis T. Barata, Sun Ying, Qiu Meng, Julia Barkans, Karalasingam Rajakulasingam, Stephen R. Durham, A.Barry Kay
Journal: Journal of Allergy and Clinical Immunology (1998)
Who Profits From Tobacco Sales to Children?
Authors: Joseph R. DiFranza
Journal: JAMA (1990)

It is estimated that more than 3 million American children under 18 years of age consume 947 million packs of cigarettes and 26 million containers of smokeless tobacco yearly. These tobacco products account for annual sales of $1.26 billion. Approximately 3% of tobacco industry profits ($221 million in 1988) derive directly from the sale of cigarettes to children, an activity that is illegal in 43 states. Approximately half of the tobacco industry's profits, or $3.35 billion annually, derives from sales to people who became addicted to nicotine as children. Tax revenues to the federal ($152 million) and state ($173 million) governments from cigarette sales to children dwarf governmental expenditures on smoking and health. We describe how dozens of communities have effectively enforced laws that prohibit the distribution of tobacco to children and offer some suggestions for increasing efforts to prevent nicotine addiction.
Gefitinib in Combination With Paclitaxel and Carboplatin in Advanced Non–Small-Cell Lung Cancer: A Phase III Trial—INTACT 2
Authors: Roy S. Herbst, Giuseppe Giaccone, Joan H. Schiller, Ronald B. Natale, Vincent Miller, Christian Manegold, Giorgio Scagliotti, Rafael Rosell, Ira Oliff, James A. Reeves, Michael K. Wolf, Annetta D. Krebs, Steven D. Averbuch, Judith S. Ochs, John Grous, Abderrahim Fandi, David H. Johnson
Journal: Journal of Clinical Oncology (2004)

Preclinical studies indicate that gefitinib (Iressa, ZD1839; AstraZeneca, Wilmington, DE), an orally active epidermal growth factor receptor tyrosine kinase inhibitor, may enhance antitumor efficacy of cytotoxics, and combination with paclitaxel and carboplatin had acceptable tolerability in a phase I trial. Gefitinib monotherapy demonstrated unparalleled antitumor activity for a biologic agent, with less toxicity than docetaxel, in phase II trials in refractory, advanced non-small-cell lung cancer (NSCLC). This phase III, randomized, placebo-controlled, double-blind trial evaluated gefitinib plus paclitaxel and carboplatin in chemotherapy-naive patients with advanced NSCLC.Patients received paclitaxel 225 mg/m(2) and carboplatin area under concentration/time curve of 6 mg/min/mL (day 1 every 3 weeks) plus gefitinib 500 mg/d, gefitinib 250 mg/d, or placebo. After a maximum of six cycles, daily gefitinib or placebo continued until disease progression. End points included overall survival, time to progression (TTP), response rate (RR), and safety evaluation. Results A total of 1,037 patients were recruited. Baseline demographic characteristics were well balanced. There was no difference in overall survival (median, 8.7, 9.8, and 9.9 months for gefitinib 500 mg/d, 250 mg/d, and placebo, respectively; P =.64), TTP, or RR between arms. Expected dose-related diarrhea and skin toxicity were observed in gefitinib-treated patients, with no new significant/unexpected safety findings from combination with chemotherapy. Subset analysis of patients with adenocarcinoma who received > or = 90 days' chemotherapy demonstrated statistically significant prolonged survival, suggesting a gefitinib maintenance effect.Gefitinib showed no added benefit in survival, TTP, or RR compared with standard chemotherapy alone. This large, placebo-controlled trial confirmed the favorable gefitinib safety profile observed in phase I and II monotherapy trials.
From muscle disuse to myopathy in COPD: potential contribution of oxidative stress
Authors: A. Couillard, C. Prefaut
Journal: European Respiratory Journal (2005)

Evidence has been accumulating that chronic inactivity leading to muscle disuse is unlikely to be the only explanation for the peripheral muscle dysfunction of chronic obstructive pulmonary disease (COPD) patients. Although a new concept of myopathy was recently proposed, the question of disuse and/or a form of myopathy is still being debated. This review proposes definitions for the terms used in this debate, discusses the relevant studies and concludes that the evidence points to a myopathy associated with muscle disuse in COPD. COPD myopathy implies pharmacological and/or pathophysiological mechanisms that need to be identified in order to optimally orient therapeutic strategies. The literature indicates that corticosteroids, inflammation, hypoxaemia and oxidative stress are among the factors contributing to COPD muscle dysfunction, but their relative contributions have not been fully elucidated. This review presents the advances in understanding each of these mechanisms, especially the data showing that muscle oxidative stress occurs and contributes to muscle dysfunction in chronic obstructive pulmonary disease. The current review also reports the studies that have elucidated the molecular mechanisms underlying this stress in chronic obstructive pulmonary disease by demonstrating alterations in oxidant and/or antioxidant systems. Finally, the review considers how inflammation and hypoxaemia may trigger oxidative stress in chronic obstructive pulmonary disease muscles and presents the therapeutic modalities that should be proposed to prevent it.
Proof-of-concept study for successful inter-laboratory comparison of MLVA results
Authors: J T Larsson, M Torpdahl, Collective MLVA working group, E Møller Nielsen
Journal: Eurosurveillance (2013)

Multiple-locus variable-number of tandem repeats analysis (MLVA) is widely used for typing of pathogens. Methods such as MLVA based on determining DNA fragment size by the use of capillary electrophoresis have an inherent problem as a considerable offset between measured and real (sequenced) lengths is commonly observed. This discrepancy arises from variation within the laboratory set-up used for fragment analysis. To obtain comparable results between laboratories using different set-ups, some form of calibration is a necessity. A simple approach is to use a set of calibration strains with known allele sizes and determine what compensation factors need to be applied under the chosen set-up conditions in order to obtain the correct allele sizes. We present here a proof-of-concept study showing that using such a set of calibration strains makes inter-laboratory comparison possible. In this study, 20 international laboratories analysed 15 test strains using a five-locus Salmonella enterica serovar Typhimurium MLVA scheme. When using compensation factors derived from a calibration set of 33 isolates, 99.4% (1,461/1,470) of the MLVA alleles of the test strains were assigned correctly, compared with 64.8% (952/1,470) without any compensation. After final analysis, 97.3% (286/294) of the test strains were assigned correct MLVA profiles. We therefore recommend this concept for obtaining comparable MLVA results.
Nebulised taurolidine and B cepacia bronchiectasis
Authors: M J LEDSON
Journal: Thorax (2000)

We have already reported a unique case of bronchiectasis with chronic colonisation by UK epidemic (ET12) Burkholderia cepacia in a previously well woman which developed following an acute infection acquired from her two B cepacia colonised children with cystic fibrosis.1 This has intermediate sensitivity to only co-trimoxazole and ceftazidime and, despite several intravenous courses of these antibiotics, the patient has remained chronically colonised for more than four years. We have therefore looked for other antibiotics which may have action against this multidrug resistant pathogen. Taurolidine acts by disrupting the cell wall, diminishing bacterial adherence, and neutralising toxins.2 It has good in vitro anti- B cepacia activity (MIC 0.4 mg/ml) but is currently used as an antiseptic peritoneal lavage solution. We gave nebulised …
Decreased Helicobacter pylori associated gastric carcinogenesis in mice lacking inducible nitric oxide synthase
Authors: Nam Kt, Oh Sy, Ahn B, Kim Yb, Jang Dd, Yang Kh, Hahm Kb, Kim Dy
Journal: Gut (2004)

<b>Background and aims:</b> Overproduction of nitric oxide via inducible nitric oxide synthase (iNOS) is suggested to be a significant pathogenic factor in <i>Helicobacter pylori</i> induced gastritis. The purpose of this study was to examine the role of iNOS in <i>H pylori</i> associated gastric carcinogenesis. <b>Methods:</b> Two types of mice were used in this study: iNOS deficient mice (iNOS−/−) and wild-type littermates. Gastric cancer was generated in mice using a combination treatment comprising <i>N</i>-methyl-<i>N</i>-nitrosourea administration and <i>H pylori</i> infection. Fifty weeks after treatment, tumours in gastric tissues from both types of mice were examined using histopathology, immunohistochemistry, and immunoblotting for iNOS and 3-nitrotyrosine. <b>Results:</b> The overall incidence of gastric cancer at week 50 was significantly lower in iNOS−/− compared with iNOS wild-type mice (p&lt;0.05). When analysed according to tumour pathology, the incidence of gastric adenocarcinoma was significantly lower in iNOS−/− compared with iNOS wild-type mice (p&lt;0.05). Immunostaining for iNOS was clearly observed in adenocarcinoma cells of iNOS wild-type mice, and was characterised by a strong cytoplasmic expression pattern. 3-Nitrotyrosine was expressed mostly in the area of the lamina propria of gastritis and adenoma lesions in iNOS wild-type mice. Immunoblotting analyses showed that iNOS and 3-nitrotyrosine were also expressed in both adenoma and adenocarcinoma tissues from iNOS wild-type mice. iNOS and 3-nitrotyrosine expression was greater in tumour tissues than in non-tumour tissues. <b>Conclusions:</b> These findings suggest that iNOS contributes to <i>H pylori</i> associated gastric carcinogenesis in mice.
The legend of cytomegalovirus and glioblastoma lives on
Authors: M. Weller, R. Soffietti, M. Brada
Journal: Neuro-Oncology (2013)

Dear Editor,

The authors indicate no conflict of interest and report no funding for this study.

The quest to find effective treatments in glioblastoma, with the exception of one agent in 20 years, continues to fail. One reason is the parading of ineffective treatments as “promising” based on flawed studies.

An underpowered randomized phase II study of valganciclovir demonstrated lack of efficacy,1 and yet a biased retrospective analysis subselecting favorable patients gets unwarranted publicity in the New England Journal of Medicine.2 Improved survival is claimed for 50 newly assembled valganciclovir patients, consisting of 22 from the experimental arm,1 8 crossover patients from the control arm1 (those who did well enough to make the crossover), and 20-odd patients treated outside a trial at the same institution.2 In all patients, valganciclovir was given only “when there was no evidence of progression” (ie, good prognosis patients). These were compared with a poorly characterized “contemporary control” group.

Looking at cytomegalovirus as a target may be reasonable, but to demonstrate efficacy of anti-cytomegalovirus strategies in glioblastoma needs well-designed prospective studies avoiding claims that are potentially misleading. On current evidence there is no justification to expose glioblastoma patients to valganciclovir outside a clinical trial.
Resistin-like molecule β regulates innate colonic function: Barrier integrity and inflammation susceptibility
Authors: Simon P. Hogan, Luqman Seidu, Carine Blanchard, Katherine Groschwitz, Anil Mishra, Margaret L. Karow, Richard Ahrens, David Artis, Andrew J. Murphy, David M. Valenzuela, George D. Yancopoulos, Marc E. Rothenberg
Journal: Journal of Allergy and Clinical Immunology (2006)
Phorbol myristate acetate stimulates phagosome-lysosome fusion in mouse macrophages.
Authors: M C Kielian, Z A Cohn
Journal: The Journal of Experimental Medicine (1981)

The effect of the tumor promoter phorbol myristate acetate (PMA) on phagosome-lysosome (P-L) fusion in mouse macrophages has been studied using a previously described (10) fluorescence assay. Treatment with 0.1--1.0 microgram PMA/ml caused a striking increase in the rate and extent of P-L fusion. Exposure of cells to phorbol, free myristate, or the monoesters of PMA did not reproduce this effect. Macrophages required from 2 to 3 h of pretreatment to express maximal P-L fusion, and this was maintained for at least 20 h when cells were returned to PMA-free medium. Catalase, superoxide dismutase, indomethacin, and hydrocortisone, agents that are known to block the effect of PMA on H2O2, O2-, prostaglandins, or plasminogen activator, did not affect the stimulation of P-L fusion by PMA. The protein-synthesis inhibitors puromycin and cycloheximide did block the PMA effect under conditions in which the high fusion rate of 4-d cells was not affected. Labeled PMA was rapidly taken up by macrophages, with a plateau of uptake at approximately 3 h. When cells were returned to PMA-free medium, cel-associated label was rapidly released, returning to background level within 1 h. The released label was found to be a metabolite of PMA by thin-layer chromatography. This product migrated between the monoester phorbol-12-myristate and free phorbol. Rapid metabolism of PMA was also observed by a macrophage cell line, J774, and, to a lesser extent, by primary rat embryo fibroblasts.
Central neural mechanisms of the cerebral ischemic response. Characterization, effect of brainstem and cranial nerve transections, and simulation by electrical stimulation of restricted regions of medulla oblongata in rabbit.
Authors: R A Dampney, M Kumada, D J Reis
Journal: Circulation Research (1979)

The cerebral ischemic response was elicited in anesthetized rabbits by briefly clamping both common carotid arteries after previously occluding the vertebral arteries.The primary cerebral ischemic response, elicited after elimination of baroreceptors, consisted of arterial hypertension, bradycardia, and apnea.The hypertension resulted from a sterotyped and differentiated pattern of vasoconstriction in renal, mesenteric, and femoral arteries.Total peripheral conductance and cardiac output were decreased.Vagotomy usually changed the bradycardia to a tachycardia unaffected by adrenalectomy.With baroreceptors intact the magnitude of the bradycardia increased and its latency decreased.The ischemic response persisted after transection of brainstem at the pontomedullary junction and/or of lower cranial nerves (except for the bradycardia which was abolished by transection of vagal rootlets).Transection of the spinal cord at Cl abolished the reflex hypertension and apnea, but not the bradycardia.Hypertension and changes of regional blood flow, comparable qualitatively and quantitatively to those elicited by ischemia, were produced by electrical stimulation of areas of the medullary reticular formation encompassing portions of the gigantocellular and parvocellular reticular nuclei.We conclude: (1) the primary cerebral ischemic response i« associated with a neurally mediated and differentiated pattern of vasoconstriction and with coactivation of the cardiac vagal and sympathetic nerves; (2) the reflex cardiac, but not vasomotor, components are secondarily modified by baroreceptor reflexes; (3) the ischemic response results from direct stimulation of neurons in the medulla oblongata; (4) the parvocellular and gigantocellular nuclei mediate the vasomotor but not the cardiac and respiratory components of the response.
Transregulation of adenylyl-cyclase-coupled inhibitory receptors in heart failure enhances anti-adrenergic effects on adult rat cardiomyocytes
Authors: M Borst
Journal: Cardiovascular Research (1999)

Objective: In congestive heart failure (CHF), a desensitisation of stimulatory β-receptors and of adenylyl cyclase in the heart is associated with an increase in inhibitory Gi proteins. To investigate whether the regulation of the Gi-mediated inhibitory side of the adenylyl cyclase system may be of functional importance in the failing myocardium, the contractile response of isolated adult cardiomyocytes to stimulation of inhibitory muscarinic M2 and A1 adenosine receptors was analysed. Methods: CHF was induced in rats by banding of the ascending aorta and was verified by doubling of lung wet weight. After four weeks, contraction amplitude (ΔL) and the velocity (dL/dtmax) of isolated ventricular cardiomyocytes during electrical field stimulation in the presence of 1 mM Ca2+ were measured using video micrometry. Results: Contractile responses of failing cardiomyocytes to 5 mM Ca2+ were unchanged. The response to increasing concentrations of the β-adrenergic agonist, isoproterenol (0.1–30 nM), and to forskolin (0.1 nM–1 μM) were significantly blunted. When A1 receptors were activated with N6-(R-phenyl-isopropyl)-adenosine (PIA; 0.01–1 μM) in the presence of 3 nM isoproterenol, contractility was unchanged in cells compared with those from sham-operated rats, but ΔL was reduced by up to 23% and dL/dtmax by 35% in failing cardiomyocytes (P<0.01), demonstrating an enhanced inhibitory effect of A1 receptors. The response to the M2 receptor agonist, carbachol (0.01–3 μM), was augmented to a comparable extent (ΔL, −22%, dL/dtmax, −39%; P<0.01). Conclusions: In CHF, the inotropic responses to β-receptor-stimulation and to direct stimulation of adenylyl cyclase, but not to Ca2+, are diminished due to desensitisation of the stimulatory side of the adenylyl cyclase signal transduction system. In parallel, the responses to inhibitory receptors are augmented, leading to a pronounced Gi-mediated negative inotropic effect on failing heart muscle cells. Those anti-adrenergic effects could contribute to the contractile dysfunction of the failing heart. Reversal of the sensitisation to inhibitory stimuli might be one of the desirable mechanisms of medical therapy in CHF.