tbuckley/cabot-search huggingface dataset:
Evaluation of Peripheral Eosinophil Counts Pre and Post-Functional Endoscopic Sinus Surgery for Nasal Polyposis in Patients with Concomitant Asthma and Allergic Rhinitis
Authors: V VANSTEE, A WOLFF
Journal: Journal of Allergy and Clinical Immunology (2008)

RATIONALE: To determine the frequency of systemic immunodeficiency in patients with objective evidence of recurrent acute rhinosinusitis (RARS) or acute exacerbations of chronic rhinosinusitis (AECRS) and to systematically review the current literature by Medline search.METHODS: Retrospective chart review of a single tertiary rhinology practice of thirty seven patients with objective evidence of RARS or AECRS who were screened with an immunodeficiency panel over a five year period as well as a Medline search of the terms RARS and AECRS combined with immunodeficiency.RESULTS: Thirteen of 37 patients (35%) were found to have an abnormal lab value suggestive of immunodeficiency.One patient (2.7%) had common variable immunodeficiency, 6 patients (16.2%) low total IgG, 2 patients (5.4%) low IgG subclass, 2 patients (5.4%) isolated cellular deficiency, 1 patient (2.7%) compliment deficiency, 1 patient (2.7%) isolated low IgM, and no patients with IgA deficiency.Three additional patients were unresponsive to the pneumococcal vaccine alone, a term known as selective antibody deficiency with normal immunoglobulins (SADNI).A major risk factor identified for RARS and AECRS in our population included exposure to young children.Six studies in the literature met our screening criteria and reported an immunodeficiency rate in similar patients of 9-27%.Unlike prior reviews, we found no IgA deficiency, but did identify low IgM and T cell deficiencies.CONCLUSIONS: Over a third of patients with RARS and AECRS demonstrate an immunologic deficiency on screening.Similar rates have been reported in the literature.We propose an immunologic screen in all patients with RARS or AECRS.
Minocycline Prevents Osmotic Demyelination Syndrome by Inhibiting the Activation of Microglia
Authors: Haruyuki Suzuki, Yoshihisa Sugimura, Shintaro Iwama, Hiromi Suzuki, Ozaki Nobuaki, Hiroshi Nagasaki, Hiroshi Arima, Makoto Sawada, Yutaka Oiso
Journal: Journal of the American Society of Nephrology (2010)

Rapid correction of chronic hyponatremia can lead to osmotic demyelination syndrome (ODS), a severe demyelination disease. The microglia that accumulate in the demyelinative lesions may play a detrimental role in the pathogenesis of ODS by producing proinflammatory cytokines, suggesting that they may be a target for therapeutic intervention. Here, we investigated whether minocycline, a selective and potent inhibitor of microglial activation, could protect against ODS in rats. We induced hyponatremia by liquid diet feeding and dDAVP infusion. Rapid correction of the hyponatremia 7 days later resulted in neurologic impairment with severe demyelinative lesions. Activated microglia accumulated at the site of demyelination. Treatment with minocycline within 24 hours of rapid correction, however, was protective: rats exhibited minimal neurologic impairment, and survival improved. Histologic analysis showed that minocycline inhibited demyelination and suppressed the accumulation of microglia at the site of demyelination. Real-time RT-PCR and immunohistochemical analyses showed that minocycline inhibited the activity of microglia and the expression of inflammatory cytokines (e.g. IL-1β, inducible nitric-oxide synthase, and TNF-α), monocyte chemoattractant protein-1, and matrix metalloproteinase-12 in microglia. These results demonstrate that minocycline can protect against ODS by inhibiting the activation and accumulation of microglia at the site of demyelinative lesions, suggesting its possible use in clinical practice.
Gene Expression Profiling Reveals a Massive, Aneuploidy-Dependent Transcriptional Deregulation and Distinct Differences between Lymph Node–Negative and Lymph Node–Positive Colon Carcinomas
Authors: Marian Grade, Patrick Hörmann, Sandra Becker, Amanda B. Hummon, Danny Wangsa, Sudhir Varma, Richard Simon, Torsten Liersch, Heinz Becker, Michael J. Difilippantonio, B. Michael Ghadimi, Thomas Ried
Journal: Cancer Research (2007)

Abstract To characterize patterns of global transcriptional deregulation in primary colon carcinomas, we did gene expression profiling of 73 tumors [Unio Internationale Contra Cancrum stage II (n = 33) and stage III (n = 40)] using oligonucleotide microarrays. For 30 of the tumors, expression profiles were compared with those from matched normal mucosa samples. We identified a set of 1,950 genes with highly significant deregulation between tumors and mucosa samples (P &amp;lt; 1e−7). A significant proportion of these genes mapped to chromosome 20 (P = 0.01). Seventeen genes had a &amp;gt;5-fold average expression difference between normal colon mucosa and carcinomas, including up-regulation of MYC and of HMGA1, a putative oncogene. Furthermore, we identified 68 genes that were significantly differentially expressed between lymph node–negative and lymph node–positive tumors (P &amp;lt; 0.001), the functional annotation of which revealed a preponderance of genes that play a role in cellular immune response and surveillance. The microarray-derived gene expression levels of 20 deregulated genes were validated using quantitative real-time reverse transcription-PCR in &amp;gt;40 tumor and normal mucosa samples with good concordance between the techniques. Finally, we established a relationship between specific genomic imbalances, which were mapped for 32 of the analyzed colon tumors by comparative genomic hybridization, and alterations of global transcriptional activity. Previously, we had conducted a similar analysis of primary rectal carcinomas. The systematic comparison of colon and rectal carcinomas revealed a significant overlap of genomic imbalances and transcriptional deregulation, including activation of the Wnt/β-catenin signaling cascade, suggesting similar pathogenic pathways. [Cancer Res 2007;67(1):41–56]
Eosinophilic infiltration of the liver in primary biliary cirrhosis: A morphological study
Authors: Shuichi Terasaki, Yasuni Nakanuma, Masakazu Yamazaki, Masashi Unoura
Journal: Hepatology (1993)

Eosinophils and their secretory proteins are important in necroinflammatory processes. In this study we surveyed eosinophilic infiltration of the liver in 176 liver biopsy specimens from patients with primary biliary cirrhosis. A considerable number of eosinophils were found in the portal tracts in 51 of these specimens (29%), whereas this finding occurred in only 2 of 50 (4%) specimens from patients with viral chronic active hepatitis. Eosinophilic infiltration of the portal tracts was focal. These eosinophils were immunohistochemically shown to contain the secreted form of eosinophilic cationic protein. Grades of eosinophilic infiltration of the portal tracts were higher in those livers with higher grades of lymphoplasmacytic infiltration, granulomas and florid duct lesion in the portal tracts, and they were lower in those livers with higher grades of bile duct disappearance and orcein-positive granuoles in hepatocytes. In the livers of patients with primary biliary cirrhosis, eosinophils were abundant around the damaged bile ducts, around the portal vein branches and at the marginal regions, and they were scattered in the portal tracts, whereas only the last pattern was seen in viral chronic active hepatitis. Peripheral blood eosinophils tended to be increased in primary biliary cirrhosis patients with higher grades of eosinophilic infiltration of the portal tracts. Eosinophilic infiltration of the portal tracts may play a role in immunological injuries of the interlobular bile ducts in primary biliary cirrhosis.
Forced oscillation technique and spirometry in cold air provocation tests.
Authors: G J Wesseling, I M Vanderhoven-Augustin, E F Wouters
Journal: Thorax (1993)

BACKGROUND: Impedance measurements by the forced pseudo random noise oscillation technique can be used to study the mechanical characteristics of the respiratory system. The objective of this study was to analyse the changes in impedance to a cold air provocation test in patients with asthma, and to correlate these changes with those in the forced expiratory volume in one second (FEV1). METHODS: The response to isocapnic hyperventilation with cold air was assessed by respiratory impedance measurements and spirometry in 60 patients with bronchial asthma in whom the provocative dose of histamine resulting in a 20% fall in FEV1 (PD20) was &lt; or = 8 mumol. RESULTS: Cold air provocation resulted in a mean(SD) fall in FEV1 from 3.75(0.85) litres to 3.10(0.90) litres. The mean(SD) decrease in FEV1 as a percentage of predicted was 15.4(3.8)%. The oscillatory resistance at 8 Hz increased from a mean(SD) of 0.367(0.108) kPa/l/s to 0.613(0.213) kPa/l/s and at 28 Hz the resistance increased from 0.348(0.089) to 0.403(0.099) kPa/l/s. Frequency dependence of resistance became significantly more negative. The reactance at 8 Hz decreased from a mean(SD) of -0.035 (0.041) kPa/l/s to -0.234(0.199) kPa/l/s, and the resonant frequency increased from 12.5(4.9) Hz to 25.7(9.1) Hz. Significant correlations were calculated between the decrease in FEV1 and changes in the various impedance parameters, especially between the decrease in FEV1 and the increase in resistance at 8 Hz (r = -0.66), and the decrease in FEV1 and the increase in the resonant frequency (r = -0.63). CONCLUSION: Cold air provocation in asthmatic subjects results in changes in the impedance of the respiratory system that correlate well with the changes in FEV1. These changes in impedance reflect ventilatory inhomogeneities in the peripheral compartment of the bronchial tree. These observations show the value of this technique in the evaluation of induced bronchoconstriction, as both a quantitative and a qualitative analysis of the response is possible.
Randomized Phase III Trial of Low-dose Isotretinoin for Prevention of Second Primary Tumors in Stage I and II Head and Neck Cancer Patients
Authors: Fadlo R. Khuri, J. Jack Lee, Scott M. Lippman, Edward S. Kim, Jay S. Cooper, Steven E. Benner, Rodger Winn, Thomas F. Pajak, Brendell Williams, George Shenouda, Ian Hodson, Karen Fu, Dong M. Shin, Everett E. Vokes, Lei Feng, Helmuth Goepfert, Waun Ki Hong
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: Isotretinoin (13- cis -retinoic acid) is a synthetic vitamin A derivative, or retinoid, widely used in the treatment of cystic acne. Preclinical and clinical studies of high-dose isotretinoin in patients with head and neck squamous cell cancer (HNSCC) have produced encouraging results. We conducted a phase III randomized trial of low-dose isotretinoin versus placebo in early-stage HNSCC patients to assess its effect on second primary tumor incidence and survival. Methods: We randomly assigned 1190 patients who had been treated for stage I or II HNSCC to receive either low-dose isotretinoin (30 mg/day) or placebo for 3 years. The patients were monitored for up to 4 more years. Survival was analyzed by the Kaplan–Meier method, and Cox proportional hazards models were used for multivariable survival analysis. All statistical tests were two-sided. Results: Isotretinoin did not statistically significantly reduce the rate of second primary tumors (hazard ratio [HR] = 1.06, 95% confidence interval [CI] = 0.83 to 1.35) or increase survival (HR = 1.03, 95% CI = 0.81 to 1.32) compared with placebo in patients with early-stage HNSCC. Current smokers had a higher rate of second primary tumors than that of never (HR = 1.64, 95% CI = 1.08 to 2.50) or former (HR = 1.32, 95% CI = 1.01 to 1.71) smokers. The hazard ratio of death from any cause for current smokers versus never smokers was 2.51 (95% CI = 1.54 to 4.10) and for current smokers versus former smokers was 1.60 (95% CI = 1.23 to 2.07). Major sites of second primary tumors (n = 261) included lung (31%), oral cavity (17%), larynx (8%), and pharynx (5%). Conclusions: Low-dose isotretinoin was not effective in reducing the rate of second primary tumors or death or smoking-related disease. Smoking statistically significantly increased the rate of second primary tumors and death. Ongoing trials are testing higher doses of isotretinoin as part of combination bioadjuvant therapeutic methods for patients with locally advanced HNSCC.
Lactobacillus GG prevents recurrence of colitis in HLA-B27 transgenic rats after antibiotic treatment
Authors: L A Dieleman
Journal: Gut (2003)

<b>Background and aims:</b><i>Bacteroides vulgatus</i> induces colitis in gnotobiotic HLA-B27 transgenic (TG) rats while broad spectrum antibiotics prevent and treat colitis in specific pathogen free (SPF) TG rats although disease recurs after treatment ends. Lactobacilli treat human pouchitis and experimental colitis. We investigated if <i>Lactobacillus rhamnosus GG</i> (<i>L GG</i>) can prevent colitis in TG rats monoassociated with <i>B vulgatus</i> and if <i>L GG</i> or <i>Lactobacillus plantarum 299v</i> (<i>LP 299v</i>) can treat established colitis in SPF TG rats and prevent recurrent disease after antibiotics were stopped. <b>Methods:</b> Germfree B27 TG rats were monoassociated with <i>B vulgatus</i> for four weeks following two weeks of colonisation with <i>L GG</i> or no bacteria. SPF B27 TG rats received oral vancomycin and imipenem for two weeks, or water alone, followed by four weeks of treatment with oral <i>L GG</i>, <i>LP 299v</i>, or water only. Disease activity was quantified by blinded gross and histological scores, caecal myeloperoxidase (MPO) activity, and levels of interleukin (IL)-1β, tumour necrosis factor (TNF), transforming growth factor β, and IL-10. <b>Results:</b><i>L GG</i> did not prevent colitis in <i>B vulgatus</i> co-associated TG rats or treat established disease in SPF rats. However, <i>L GG</i> but not <i>LP 299v</i> prevented colitis relapse in antibiotic treated rats with reduced gross and histological scores, caecal MPO, IL-1β, and TNF whereas caecal IL-10 was increased. <b>Conclusions:</b><i>L GG</i> does not prevent colitis in gnotobiotic TG rats or treat established disease in SPF rats, but is superior to <i>LP 299v</i> in the prevention of recurrent colitis. These studies suggest that antibiotics and probiotic agents provide synergistic therapeutic effects, perhaps mediated by altered immunomodulation with selective activity of different lactobacillus species.
Pulmonary valve incompetence: I. Evaluation using electromagnetic flow velocity catheters and a new valve insufficiency analyser
Authors: F. VAN DER MARK, J. ROHMER, W. G. ZIJLSTRA
Journal: Cardiovascular Research (1976)

In animal experiments regurgitant flow through competent and incompetent pulmonary valves was evaluated with electromagnetic flow velocity catheters by using the ratio of the separately integrated backward and forward flow velocity signals. This ratio was obtained with a special purpose analog computing circuit set by an in-vitro zero flow reference signal, which was in good agreement with in-vivo zero flow signals.
Intestinal fatty acid infusion modulates food preference as well as calorie intake via the vagal nerve and midbrain–hypothalamic neural pathways in rats
Authors: Nobuya Ogawa, Makoto Ito, Hideki Yamaguchi, Tetsuya Shiuchi, Shiki Okamoto, Korekiyo Wakitani, Yasuhiko Minokoshi, Masamitsu Nakazato
Journal: Metabolism (2012)
Cardiac plasma membrane physical properties and β-adrenergic receptor function are unaltered in portal-hypertensive rats
Authors: Zenghua Ma, Jonathan B. Meddings, Samuel S. Lee
Journal: Hepatology (1995)

We have previously demonstrated that impairment of cardiac contractility in a rat model of cirrhosis may be secondary to altered cardiac plasma membrane physical properties affecting beta-adrenergic receptor function. It is unclear whether this is caused by the cirrhosis or by the portal hypertension in this model, so we studied cardiomyocyte plasma membrane physical properties, lipid composition, and beta-adrenergic receptor function in a rat model of prehepatic portal hypertension without cirrhosis. Portal hypertension was induced by graded portal vein stenosis, whereas controls had a sham operation. Cardiac sarcolemmal plasma membrane physical properties were studied by fluorescent polarization methods using diphenylhexatriene and a series of anthroyloxy-stearic acids to estimate, respectively, the static and dynamic components of membrane fluidity. beta-Adrenergic receptor density and binding affinity were measured using 3H-dihydroalprenolol as a radioligand. Isoproterenol-stimulated adenylyl cyclase activity was measured by radioimmunoassay. Neither the static nor the dynamic components of membrane fluidity were significantly different in portal-hypertensive rats compared with the controls. The membrane cholesterol, phospholipid content, and the cholesterol/phospholipid ratio did not differ between the two groups. beta-Adrenergic receptor density and binding affinity in the portal-hypertensive rats (respectively, 1.65 +/- 0.06 pmol/mg protein and 6.78 +/- 0.80 nmol/L) were not different from controls (1.76 +/- 0.17 pmol/mg protein and 7.25 +/- 1.48 nmol/L). Isoproterenol-stimulated adenylyl cyclase activity in membranes from portal-hypertensive rats did not significantly differ from controls. We conclude that cardiac plasma membrane physical properties and beta-adrenoceptor function in portal hypertensive rats remains unimpaired, suggesting that the cardiomyopathy of cirrhosis is not caused by portal hypertension per se.
Use of GRADE grid to reach decisions on clinical practice guidelines when consensus is elusive
Authors: R. Jaeschke, G. H Guyatt, P. Dellinger, H. Schunemann, M. M Levy, R. Kunz, S. Norris, J. Bion
Journal: BMJ (2008)

<h3>Abstract</h3> Flavin containing monooxygenases (FMOs) are promiscuous enzymes known for metabolizing a wide range of exogenous compounds. In <i>C. elegans</i>, <i>fmo-2</i> expression increases lifespan and healthspan downstream of multiple longevity-promoting pathways through an unknown mechanism. Here, we report that, contrary to its classification as a xenobiotic enzyme, <i>fmo-2</i> expression leads to rewiring of endogenous metabolism principally through changes in one carbon metabolism (OCM). Using computer modeling, we identify decreased methylation as the major OCM flux modified by FMO-2 that is sufficient to recapitulate its longevity benefits. We further find that tryptophan is decreased in multiple mammalian FMO overexpression models and is a validated substrate for FMO enzymes. Our resulting model connects a single enzyme to two previously unconnected key metabolic pathways and provides a framework for the metabolic interconnectivity of longevity-promoting pathways such as dietary restriction. FMOs are well-conserved enzymes that are also induced by lifespan-extending interventions in mice, supporting a conserved and critical role in promoting health and longevity through metabolic remodeling.
Author's response to Persson letter
Authors: Sally Wenzel
Journal: Thorax (2012)

Dr Persson raises excellent points regarding the potential for epithelial cells to contribute to the clearance of eosinophils from tissue.We are in agreement that eosinophils can migrate from bone marrow to blood to submucosa to epithelium to lumen.However, the speed of the process, the role and response of each compartment, the stimulus for it and its overall control remain poorly understood.Dr Persson suggests that previous reports show an inverse relationship of tissue compared with luminal/epithelial eosinophils following allergen challenge such that the accumulation of eosinophils in the lumen equates to resolution of inflammation.This suggests to him that the epithelium plays a resolving role.
Interactions of vasopressin with the area postrema in arterial baroreflex function in conscious rabbits.
Authors: K P Undesser, E M Hasser, J R Haywood, A K Johnson, V S Bishop
Journal: Circulation Research (1985)

This study compares the effect of arginine-vasopressin with phenylephrine on arterial pressure, heart rate, and renal sympathetic nerve activity in conscious rabbits with and without functional arterial baroreflexes and in rabbits with lesions of the area postrema. In intact rabbits, progressive infusions of arginine-vasopressin result in large decreases in renal sympathetic nerve activity and heart rate for a given increase in blood pressure as compared to progressive infusions of phenylephrine. In sinoaortic-denervated rabbits, the responses of arterial pressure on heart rate and renal sympathetic nerve activity to both arginine-vasopressin and phenylephrine are markedly attenuated, indicating the necessity for afferent baroreceptor activity in this response. This observation indicates that arginine-vasopressin is acting centrally to enhance the baroreflex. A central site of action of circulating vasopressin may be the area postrema, since it is the only circumventricular organ in the hindbrain. Lesioning the region of the area postrema resulted in a normalization of the responses evoked with arginine-vasopressin and phenylephrine. There was no difference in the phenylephrine responses of arterial pressure on renal sympathetic nerve activity or heart rate in area postrema-lesioned animals, compared to control rabbits. Therefore, we conclude that the area postrema or its surrounding tissue is either a site of action of circulating arginine-vasopressin or contains fibers of passage from another site where arginine-vasopressin acts to enhance baroreflex activity.
Bio-radiation dermatitis: the need of a new grading: in regard to Bernier et al: Ann Oncol 2011; 22(10): 2191–2200
Authors: E.G. Russi, R.-J. Bensadoun, M.C. Merlano, J. Bourhis, U. Ricardi, J. Giralt, C. Pinto, W. Budach, R. Corvò, M.E. Lacouture, J. Bernier
Journal: Annals of Oncology (2013)
Autoimmunity in rheumatoid arthritis: different antigens—common principles
Authors: L A Trouw, Tom W J Huizinga, René E M Toes
Journal: Annals of the Rheumatic Diseases (2012)

Since the identification of antibodies directed against citrullinated protein antibodies (ACPA) as specific serological markers for rheumatoid arthritis (RA) the insight into the pathogenesis of RA has made significant progress. It is now realised that RA does not represent one disease entity, as ACPA-positive and ACPA-negative RA differ in several important aspects. For example, the most prominent genetic risk factors, the human leucocyte antigen shared epitope alleles only predispose to ACPA-positive RA, but not to ACPA-negative disease. Likewise, ACPA-positive RA is characterised by a more severe disease course as well as by a lower chance to enter drug-free remission. More recently, it became apparent that next to ACPA, another autoantibody system is also present in RA patients that is directed against a structurally similar determinant. These antibodies recognise carbamylated proteins and thus are called anticarbamylated protein (anti-CarP) antibodies. During carbamylation lysine residues are post-translationally modified to a homocitrulline, the antigenic identity crucial for recognition by anti-CarP antibodies. In this review we will discuss novel insight into the immune responses directed against citrullinated and carbamylated proteins.
Health professionals should do more to prevent children ending up in custody, BMA says
Authors: J. Wise
Journal: BMJ (2014)

Vulnerable children and teenagers are continually let down by health and social care services, and it is inevitable that many end up in the criminal justice system, warns the British Medical Association.

Its new report, Young Lives Behind Bars , says that many young people in custody come from chaotic backgrounds and are often the victims of violence, abuse, or neglect.1 It recommends that health professionals carry out early screening and identification …