tbuckley/cabot-search huggingface dataset:
Latent tuberculosis among health care workers in Denmark estimated by IGRA
Authors: Sidse Graff Jensen, Jon Torgny Wilcke, Niels Seersholm
Journal: European Respiratory Journal (2013)

Background:  Health care workers (HCWs) treating patients with tuberculosis (TB) are at risk of becoming infected. Hence periodical screening of HCWs is a part of TB control programs in low incidence countries. Evidence of the utility of Interferon gamma release assays (IGRAs) in diagnosing latent TB is growing.   Aim:  The aim of the study was to estimate the prevalence of latent tuberculosis and the within subject variability of IGRA among health care workers with known exposure to TB at work in a TB low incidence country.   Methods:  Employees working at the pulmonary ward and as radiographers in Gentofte Hospital in Copenhagen (approximately 150 treated TB patients/year) were invited to participate. They completed a questionnaire and blood samples for IGRA-testing (QuantiFERON®, cellestis) were drawn twice with an interval of two weeks.   Results:  130 persons participated. Eight (6,2%) had two positive quantiferon tests and of these four had no history of TB exposure other than at work. One had been traveling, but not living or working, in TB high incidence countries. One had previously been treated for pulmonary TB, which was presumed work-related. Two of them had been living in TB high incidence countries. Two persons, who had been living in Tb-high incidence countries, had one positive and one inconclusive test. Two persons (1,5%) who initially had negative tests, was tested positive after two weeks.  Conclusion:  HCWs do have a occupational risk of becoming latently infected with TB. Whether and under which circumstances IGRA tests can be used to screen healthcare workers for latent TB awaits further studies on IGRAs used for serial testing.
Chronic Perianal Pain: An Unsolved Problem
Authors: M E Neill, M Swash
Journal: Journal of the Royal Society of Medicine (1982)

Thirty-five patients with chronic anal pain of obscure origin are described. This syndrome is ill-defined and treatment is unsatisfactory. There is a high incidence of sciatica and of damage to the pelvic floor musculature, but although the pain has features consistent with a neuralgia, its cause is unknown.
STUDIES ON PNEUMOCOCCUS GROWTH INHIBITION
Authors: Oswald H. Robertson, Richard H. P. Sia
Journal: The Journal of Experimental Medicine (1924)

Somewhat discordant results which have been reported by others who have investigated the property of the whole blood of resistant animals to cause inhibition of growth or death of pneumococci have led us to investigate this matter and to develop a new technique in which the conditions as they are present in the animal body are more nearly imitated. The observations already made have rendered it probable that phagocytosis plays some rôle in any destructive power for pneumococcus which whole blood possesses. We have, therefore, employed mixtures of serum and leucocytes in our tests, since when blood is coagulated the conditions become highly artificial. Furthermore, in order to imitate more nearly the conditions in the circulating blood the mixtures have been constantly, though gently, agitated. For this purpose a specially devised apparatus has been employed. The mixtures of serum and leucocytes have been inoculated with varying numbers of pneumococci in the active growth phase and after varying intervals of time the tubes containing the mixtures of serum, leucocytes, and bacteria have been opened, examined microscopically, and cultures made. Employing this technique it has been found that the growth of pneumococci having low virulence for cats is markedly inhibited in mixtures of cat serum and cat leucocytes. It was impossible to recover pneumococci from the tubes showing no apparent growth, either when the contents were transplanted into various kinds of culture media, or when the contents were injected into mice of a variety highly susceptible to pneumococcus infection. 10,000 times the number of pneumococci sufficient ordinarily to kill a mouse failed to do so after a 24 hour sojourn in the cat serum-leucocyte mixture. Mixtures of dog serum and leucocytes exert a similar action. The serum and leucocytes of animals susceptible to pneumococcus infection (rabbits and guinea pigs,) on the other hand, failed to injure pneumococci even in extremely small quantities. These results indicate that the blood of resistant animals, at least of the dog and cat, possesses destructive properties for pneumococci, and that this destructive power is not possessed by the blood of certain susceptible animals. The experiments suggest that natural immunity depends chiefly, if not entirely, upon this property. The leucocytes play an active part in this process, but whether the destruction of the pneumococci occurs entirely within the leucocytes or not is not determined. That the serum also plays a part is shown by the fact that when the serum of resistant animals was inactivated before being used in the serum-leucocyte mixture, the growth of even very small numbers of pneumococci was not prevented. Further experiments with cat serum and leucocytes were carried out to determine the optimum rate and time of agitation, the amount of serum and leucocytes required, and also the period of incubation necessary for the inhibition of growth and death of the pneumococci to occur.
Human monoclonal antibodies to a novel kidney cancer antigen inhibit target-induced angiogenesis and tumor cell growth and migration in vitro
Authors: Steven Kanner, Nandini Ganguly, Kendall Morrison, Juan Perez-Villar, Karen Morrison, Arthur Raitano, Pia Challita-Eid, Daulet Satpaev, Xiao-Chi Jia, Jean Gudas, Aya Jakobovits
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4108 

We have identified a novel human cell surface protein, AGS-16, that is expressed in >95% of kidney cancers, predominantly in clear cell and papillary carcinomas. AGS-16 is expressed homogeneously at high levels in primary kidney cancers and in kidney metastases to lymph nodes and lung tissues. Amongst normal tissues, AGS-16 is expressed predominantly in kidney proximal tubules. In vitro studies with a purified extracellular domain (ECD) protein and AGS-16 expressing cells have indicated an involvement of AGS-16 in angiogenesis and tumor cell proliferation and migration. AGS-16 ECD induced human umbilical vein endothelial cell (HUVEC) tube formation on Matrigel in vitro , as well as their migration in a transwell chamber assay. RNAi silencing of AGS-16 expression in the kidney clear cell line RXF-393 and the liver cancer cell line HepG2 significantly reduced their proliferation, survival, migration and invasion. XenoMouse® technology was employed to generate a large panel of high affinity fully human MAbs to AGS-16 with diverse isotypes (IgG1κ, IgG1λ, IgG2κ). Among the MAbs that demonstrated potent activity in all of the in vitro assays described above was AGS-16M18, an IgG1λ MAb with a Kd = 2.6 x 10-10M for cell surface AGS-16. AGS-16 M18 inhibited proliferation and survival of both RXF-393 and HepG2 tumor cell lines in a dose-dependent manner. In addition, AGS-16M18 dose-dependently inhibited ECD-induced HUVEC tube formation. AGS-16M18 inhibited HepG2 cell migration and invasion in a short time period, which preceded the anti-proliferative effect of the MAb on these tumor cells. Completion of studies evaluating the anti-tumor efficacy of AGS-16M18 in vivo is underway. Together, these data establish AGS-16 as an attractive target for MAb-directed therapy of kidney cancer.
Adherence with inhaled respiratory therapeutics is associated with reduced acute exacerbations of chronic obstructive pulmonary disease
Authors: Richard Mularski, MaryAnn McBurnie, Jerena Donovan, Kari Walker, Suzanne Gillespie, Vollmer William
Journal: European Respiratory Journal (2011)

Background:  Adherence to inhaled chronic obstructive pulmonary disease (COPD) medications is variable and generally low. We examined the association of medication adherence with subsequent acute exacerbations (AE) among adult members of a large health maintenance organization.   Methods:  We used data from electronic medical records to identify individuals with COPD defined by ICD-9 coded encounters during the period 2000-2008 and computed modified medication possession ratio (mMPR) to measure adherence to three classes of inhaled COPD medications. Using Cox regression, we evaluated the association between six-month adherence score (calculated forward from index date) and subsequent risk of first AE-COPD within 12 months, adjusting for age, race, sex, baseline smoking status, body habitus, and co-morbidities. AE-COPD was defined by outpatient/emergency encounters with steroid use or hospitalization.   Results:  We identified 26,516 individuals with COPD (59% female, mean age 61±13 years) of whom 80% contributed adherence data. Adherence rates (mMPR±S.D, number contributing) were 0.62±0.34, n=11317 for anticholinergics (Ach), 0.61±0.32, n=17018 for inhaled corticosteroids (ICS), and 0.66±0.29, n=5336 for long-acting beta-agonists (LABA). The relative risk for subsequent AE based on a 0.20 difference in mMPR at the start of follow-up was 0.86 (95% CI=0.84, 0.93) for ICS, 0.91 (0.84, 1.00) for LABA, and 0.89 (0.84, 0.93) for Ach.   Conclusions:  Better adherence to any of the major classes of inhaled controller therapeutics reduced the risk of subsequent AE-COPD.  Funding: Investigator Initiated Grant, Novartis Pharmaceuticals Corporation.
Abstract 2927: Long QT Syndrome as a Cause of Stillbirths
Authors: Lia Crotti, Roberto Insolia, Alice Ghidoni, Patrizio Antonazzo, Fabio Facchinetti, Irene Cetin, Peter J Schwartz
Journal: Circulation (2007)

Background : Stillbirths (intrauterine fetal deaths occurring after the 22 th week of gestation) notably contribute to perinatal mortality. Among them, 25–50% of cases remain unexplained after thorough investigation. We recently demonstrated that 10% of Sudden Infant Death Syndrome (SIDS) cases carry functionally relevant genetic variants in Long QT Syndrome (LQTS) genes. We previously hypothesized that severe forms of LQTS could contribute to mortality not only shortly after birth but also before. Accordingly, we are now screening LQTS genes in unexplained stillbirths. Materials and Methods : We receive DNA from an ongoing Italian multicenter study on rigorously defined ``unexplained stillbirths”. DNA is extracted from placenta or umbilical cord. Through DHPLC and sequence analysis we screen the main LQTS genes: KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2. Any amino-acid substitution identified in the samples is checked in a control population of 122 Caucasian controls. Here, we report the preliminary data on the first 17 cases (gestational age of death: 23–38 weeks). Results : A total of 3 missense mutations have been identified in 3 of 17 stillbirths (18%). Two were on SCN5A and one on KCNH2 . The two mutations on SCN5A (V1951L; P2006A) have been previously associated to SIDS and shown to increase the late sodium current. The mutation on KCNH2 is a novel genetic variant absent in 244 reference alleles and never described in any control populations. We are currently performing the electrophysiological cellular studies to define its functional effect. Conclusions : The initial data from this ongoing study already indicate that a yet to be defined but potentially significant number of currently unexplained intrauterine fetal deaths might be caused by ion channel diseases such as LQTS. The completion of our study will soon provide a reliable quantification of this contribution. There are potentially important implications for the affected families, ranging from prevention of recurrences to identification of other affected family members and to possible prevention of SIDS or later sudden deaths in subsequent siblings.
Pathogenic Mechanisms in Lupus Nephritis: Nucleosomes Bind Aberrant Laminin β1 With High Affinity and Colocalize in the Electron‐Dense Deposits
Authors: Anders I. Olin, Matthias Mörgelin, Lennart Truedsson, Gunnar Sturfelt, Anders A. Bengtsson
Journal: Arthritis & Rheumatology (2013)

Apoptotic nucleosomes are structurally and immunologically involved in lupus nephritis. The purpose of this study was to examine the expression and function of laminins and their interactions with nucleosomes in the kidneys of patients with lupus nephritis, using surface plasmon resonance (SPR) analysis.SPR interaction analysis was used to quantify the strength of laminin-nucleosome interactions. Electron microscopy techniques were used to determine in vivo colocalization of IgG, chromatin, and laminin β1, as well as to characterize nucleosome-laminin interactions in vitro.Nucleosomes were found to possess high affinity for laminin β1-containing laminins and to have the potential to form stable molecular complexes with these structures. In vivo, laminin β1 was aberrantly expressed in the glomerular basement membrane (GMB) of lupus nephritis patients, and in situ, it acted as a nucleosome ligand, selectively colocalizing with nucleosomes within electron-dense deposits (EDDs). Normal adult laminin 11, which contains laminin β2, did not bind nucleosomes, and it did not colocalize in vivo with the nucleosomes in the nephritic GBM. In addition, TGFβ1 was expressed by the glomerular mesangium, glomerular endothelial cells, and by podocytes in patients with lupus nephritis. It was trapped in situ within EDDs by an as-yet-unknown ligand. As was recently described in a transgenic mouse model, paracrine kidney glomerular TGFβ1 may thereby contribute to the development of glomerulopathy via the induction of laminin β1 incorporation in the GBM, whereas systemic blood vessel-derived TGFβ1 could be trapped during filtration.Our findings of the specific high-affinity binding of nucleosomes to aberrantly expressed laminin β1 in the GBM and their colocalization in the GBM may explain important features of the initial steps in the pathogenesis of lupus nephritis, the planted antigen hypothesis.
Population Pharmacokinetic Model for Topotecan Derived From Phase I Clinical Trials
Authors: James M. Gallo, Paul B. Laub, Eric K. Rowinsky, Louise B. Grochow, Sharyn D. Baker
Journal: Journal of Clinical Oncology (2000)

To characterize the pharmacokinetics of topotecan in a population model that would identify patient variables or covariates that appreciably impacted on its disposition.All data were collected from 82 patients entered in four different phase I trials that were previously reported as separate studies from 1992 to 1996. All patients received topotecan as a 30-minute constant-rate infusion on a daily-times-five schedule and were selected for this study because their daily dose did not exceed 2.0 mg/m(2). Among the 82 patients were 30 patients classified as having renal insufficiency and 13 patients with hepatic dysfunction. The population pharmacokinetic model was built in sequential manner, starting with a covariate-free model and progressing to a covariate model with the aid of generalized additive modeling.A linear two-compartment model characterized total topotecan plasma concentrations (n = 899). Four primary pharmacokinetic parameters (total clearance, volume of the central compartment, distributional clearance, and volume of the peripheral compartment) were related to various combinations of covariates. The relationship for total clearance (TVCL [L/h] = 32.0 + [0.356(WT - 71) + 0.308(HT - 168.5) - 8.42(SCR - 1.1)] x [1 + 0.671 sex]) was dependent on the patients' weight (WT), height (HT), serum creatinine (SCR), and sex and had a moderate ability to predict (r(2) = 0.64) each patient's individual clearance value. The addition of covariates to the population model improved the prediction errors, particularly for clearance. Removal of 10 outlying patients from the analysis improved the ability of the model to predict individual clearance values (r(2) = 0.77).A population pharmacokinetic model for total topotecan has been developed that incorporates measures of body size and renal function to predict total clearance. The model can be used prospectively to obtain a revised and validated model that can then be used to design individualized dosing regimens.
Impairment of membranous and vascular components of pulmonary diffusion and plasma endothelin-1 in patients with liver cirrhosis with and without COPD
Authors: Susann Langwieler, Thomas Wex, Malfertheiner Peter, Jens Schreiber
Journal: European Respiratory Journal (2011)

Liver cirrhosis (LC) may be rarely complicated by hepatopulmonary syndrome or hypertension. Nevertheless abnormalities of gas exchange are frequent in LC. The mechanisms are still unclear. A reduced hepatic clearance of Endothelin – 1 (ET-1) might play a role.  In 72 pts. with LC, 29 (40.3%) of whom had accompanying COPD, PFT were performed as well as measurements of PAaDO 2 , diffusion capacity, pulmonary capillary blood volume (Qc), membrane diffusing capacity (Dm) and plasma ET-1. The functional measurements were performed in a matched group of pts. with COPD without liver function impairment (n=38).  None of the pts. had clinically manifest hepatopulmonary syndrome or hypertension. Nevertheless 59/72 (81.9%) of the pts. with LC and all pts. with both LC and COPD and 31/39 (79,5%) pts. with sole COPD showed decreased TLCO. In all pts. but one with sole LC Dm was reduced. Qc was reduced to a lesser extend in 47 (65.2%) pts., with a greater impairment of Dm. In the COPD group the reduction of Dm was the overwhelming mechanism of an abnormal diffusion capacity. PAaDO 2  was significantly negatively correlated with TLCO, Qc and to a lesser extend with Dm in pts. with LC without ventilatory impairment. All pts. with LC independently on coexisting COPD showed increased plasma concentratons of ET-1, which were negatively correlated with Qc (r=-0.57, p=0.015).  Impairment of the Dm as well as decreased Qc are responsible for an abnormal gas exchange in pts. with LC contrary to COPD where reduction of Dm plays the most important role. Increased ET-1 in LC might contribute to pathogenesis of gas exchange impairment in LC.
Risk factors for colonization with extended-spectrum beta-lactamase-producing enterobacteriaceae on admission to rehabilitation centres
Authors: E. Bilavsky, E. Temkin, Y. Lerman, A. Rabinovich, J. Salomon, C. Lawrence, A. Rossini, A. Salvia, J.V. Samso, J. Fierro, M. Paul, J. Hart, M. Gniadkowski, M. Hochman, M. Kazma, A. Klein, A. Adler, M.J. Schwaber, Y. Carmeli
Journal: Clinical Microbiology and Infection (2014)
Prognostic Value of Myocardial Viability by Delayed-Enhanced Magnetic Resonance in Patients With Coronary Artery Disease and Low Ejection Fraction
Authors: Bernhard L. Gerber, Michel F. Rousseau, Sylvie A. Ahn, Jean-Benoît le Polain de Waroux, Anne-Catherine Pouleur, Thomas Phlips, David Vancraeynest, Agnès Pasquet, Jean-Louis J. Vanoverschelde
Journal: Journal of the American College of Cardiology (2012)
Gemcitabine Treatment in Pretreated Cutaneous T-Cell Lymphoma: Experience in 44 Patients
Authors: Pier Luigi Zinzani, Gianandrea Baliva, Massimo Magagnoli, Maurizio Bendandi, Gino Modugno, Filippo Gherlinzoni, Giulio Fraternali Orcioni, Stefano Ascani, Romeo Simoni, Stefano A. Pileri, Sante Tura
Journal: Journal of Clinical Oncology (2000)

To evaluate the efficacy and toxicity of gemcitabine, a novel pyrimidine antimetabolite with a low-toxicity profile and activity in several solid tumors, in patients with relapsed or refractory cutaneous T-cell lymphomas.Between May 1997 and February 1999, 44 previously treated patients with mycosis fungoides (MF; n = 30) and peripheral T-cell lymphoma unspecified (PTCLU) with exclusive skin involvement (n = 14) were enrolled onto a two-institution, phase II trial and treated with gemcitabine. This drug was given on days 1, 8, and 15 of a 28-day schedule at a dose of 1,200 mg/m(2) intravenously over 30 minutes for a total of three courses.Of the 44 patients, five (11. 5%) achieved complete responses (CRs), 26 (59%) partial responses (PRs), and the remaining 13 showed no benefit from the treatment. Two of the CRs were histologically confirmed. The CR and PR rates were the same for patients with MF and those with PTCLU, respectively. No difference in terms of overall response rate was observed between relapsed and refractory patients. The median durations of CR and PR were 15 months (range, 6 to 22 months) and 10 months (range, 2 to 15 months), respectively. Treatment was well tolerated; hematologic toxicity was mild, and no nausea/vomiting or organ toxicity was recorded.The results of the present phase II study show activity of gemcitabine as a single agent in patients with pretreated cutaneous T-cell lymphoma. Further studies that use gemcitabine alone or in combination with other drugs in earlier stages of the disease are needed.
Electron Microscopy of Sclerosing Adenosis and Infiltrating Duct Carcinoma of the Human Mammary Gland&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: S. R. Wellings, P. Roberts
Journal: JNCI Journal of the National Cancer Institute (1963)

Journal Article Electron Microscopy of Sclerosing Adenosis and Infiltrating Duct Carcinoma of the Human Mammary Gland Get access S. R. Wellings, S. R. Wellings Department of Pathology, The University of Oregon Medical School, Portland, Oregon Search for other works by this author on: Oxford Academic PubMed Google Scholar P. Roberts P. Roberts Department of Pathology, The University of Oregon Medical School, Portland, Oregon Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 30, Issue 2, February 1963, Pages 269–287, https://doi.org/10.1093/jnci/30.2.269 Published: 01 February 1963 Article history Received: 24 July 1962 Published: 01 February 1963
Can mediastinoscopy after negative endosonography in lung cancer be omitted? Subanalysis of ASTER with focus on PET
Authors: Kurt Tournoy, Christophe Dooms, Robert Rintoul, Ellen Deschepper, Jouke Annema
Journal: European Respiratory Journal (2011)

Background: Mediastinal staging in non-small cell lung cancer with endosonography (EUS-FNA plus EBUS-TBNA) followed by mediastinoscopy is more sensitive to detect nodal metastasis as compared to mediastinoscopy alone (ASTER trial, JAMA 2010;304:2245). However 11 patients need to undergo a mediastinoscopy to detect one with N2/3 missed by endosonography. We analysed if FDG-PET identifies patients in whom the mediastinoscopy can be omitted.  Methods: In ASTER, 123 patients were randomized to endosonography followed by mediastinoscopy when the former did not show mediastinal metastasis. Sensitivity, negative predictive value (NPV) and number of mediastinoscopies needed to detect one false negative endosonography were calculated in the cases with complete data (n=120; 98%).  Results: With PET, 77 patients had FDG-avid mediastinal nodes; the prevalence of N2/3 was 73 (62-81)%. The sensitivity and NPV of endosonography was 88 (76-94) and 75 (57-88)%. Adding mediastinoscopy increased sensitivity and NPV to 96 (88-99) and 91 (73-98)%. 43 patients did not have FDG-avid mediastinal nodes, the prevalence of N2/3 was 23 (13-38)%. The sensitivity and NPV of endosonography was 70 (40-89)% and 92 (78-97)%. Adding mediastinoscopy increased sensitivity and NPV to 80 (49-94)% and 94 (81-98)%. In patients with FDG-avid vs. FDG-cold mediastinal nodes, the number of mediastinoscopies needed to detect one false negative endosonography is 6 vs 36 (p=0.078).  Conclusions: A negative endosonography should be followed by a mediastinoscopy if PET positive mediastinal nodes are present. In the absence of PET positive nodes, a mediastinoscopy following a negative endosonography can be omitted.