tbuckley/cabot-search huggingface dataset:
Whole‐Exome Sequencing Reveals Overlap Between Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis and Familial Hemophagocytic Lymphohistiocytosis
Authors: Kenneth M. Kaufman, Bolan Linghu, Joseph D. Szustakowski, Ammar Husami, Fan Yang, Kejian Zhang, Alexandra H. Filipovich, Ndate Fall, John B. Harley, N. R. Nirmala, Alexei A. Grom
Journal: Arthritis & Rheumatology (2014)

Objective Macrophage activation syndrome (MAS), a life‐threatening complication of systemic juvenile idiopathic arthritis (JIA), resembles familial hemophagocytic lymphohistiocytosis (HLH), a constellation of autosomal‐recessive immune disorders resulting from deficiency in cytolytic pathway proteins. We undertook this study to test our hypothesis that MAS predisposition in systemic JIA could be attributed to rare gene sequence variants affecting the cytotolytic pathway. Methods Whole‐exome sequencing was used in 14 patients with systemic JIA and MAS and in their parents to identify protein‐altering single‐nucleotide polymorphisms/indels in known HLH‐associated genes. To discover new candidate genes, the entire whole‐exome sequencing data were filtered to identify protein‐altering, rare recessive homozygous, compound heterozygous, and de novo variants with the potential to affect the cytolytic pathway. Results Heterozygous protein‐altering rare variants in the known genes ( LYST, MUNC13‐4 , and STXBP2 ) were found in 5 of 14 patients with systemic JIA and MAS (35.7%). This was in contrast to only 4 variants in 4 of 29 patients with systemic JIA without MAS (13.8%). Homozygosity and compound heterozygosity analysis applied to the entire whole‐exome sequencing data in systemic JIA/MAS revealed 3 recessive pairs in 3 genes and compound heterozygotes in 73 genes. We also identified 20 heterozygous rare protein‐altering variants that occurred in at least 2 patients. Many of the identified genes encoded proteins with a role in actin and microtubule reorganization and vesicle‐mediated transport. “Cellular assembly and organization” was the top cellular function category based on Ingenuity Pathways Analysis ( P &lt; 3.10 × 10 −5 ). Conclusion Whole‐exome sequencing performed in patients with systemic JIA and MAS identified rare protein‐altering variants in known HLH‐associated genes as well as in new candidate genes.
24-hour blood pressure monitoring and 10 years systemic coronary risk evaluation in patients with bronchial asthma
Authors: Nina Karoli, Andrey Rebrov, Anna Roschina
Journal: European Respiratory Journal (2013)

The aim of our work was to study The risk of 10 years Systemic Coronary Risk Evaluation in patients with bronchial asthma with different group arterial hypertension (AH). 

We performed 24-hour blood pressure monitoring in 110 patients with stable asthma (average age 44,94±11.05 years). 85 patient had self-reported arterial hypertension (AH). Patient with was divided to 3 groups: without AH (26 pts), with stable (19 pts) and non-stable (65 pts) AH. Pts with stable AH had previously reported blood pressure elevated and high systolic and/or diastolic BP by 24-hour blood pressure monitoring (mean 24-hour systolic BP ≥125 mm Hg, diastolic BP≥80 mm Hg) . Patients with non-stable AH had previously reported blood pressure elevated in asthma attacks, asthma exacerbations, but by 24-hour blood pressure monitoring mean 24-hour systolic BP <125 mm Hg, diastolic BP<80 mm Hg . 

The estimation of 10-year's risk of fatal complications estimated (SCORE - Systemic Coronary Risk Evaluation) at the patients with stable and non-stable AH was increased compared with pts without AH.

We noted correlation between SCORE and night-time and 24-h systolic BP (ρ=0,29, p<0,05; ρ=0,29, p<0,05), night-time, day-time and 24-h diastolic BP (ρ=0,34, p<0,05; ρ=0,31, p<0,05, ρ=0,34, p<0,05) in this group pts.

Thus, the risk of 10 years' risk of death from CAD at the patients with asthma and AH without manifestations CAD are moderate. Patient with non-stable and stable AH had increased 10-year's risk of fatal complications estimated.
High-dose radiation therapy and neoadjuvant plus concomitant chemotherapy with 5-fluorouracil and cisplatin in patients with locally advanced squamous-cell anal canal cancer: Final results of a phase II study
Authors: D. Peiffert, M. Giovannini, M. Ducreux, P. Michel, E. François, C. Lemanski, X. Mirabel, F. Cvitkovic, E. Luporsi, T. Conroy, J.-P. Gérard
Journal: Annals of Oncology (2001)
Tumor Cell Cytotoxicity by Granulocytes From Peripheral Blood of Tumor-Bearing Mice 2
Authors: Bernard Fisher, Elizabeth A. Saffer
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Tumor Cell Cytotoxicity by Granulocytes From Peripheral Blood of Tumor-Bearing Mice Get access Bernard Fisher, M.D., Bernard Fisher, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Elizabeth A. Saffer, B.A. Elizabeth A. Saffer, B.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 60, Issue 3, March 1978, Pages 687–691, https://doi.org/10.1093/jnci/60.3.687 Published: 01 March 1978 Article history Received: 18 July 1977 Accepted: 14 October 1977 Published: 01 March 1978
Heart failure in patients with atrial fibrillation in Europe: a report from the <scp>EURObservational</scp> Research Programme Pilot survey on Atrial Fibrillation
Authors: Gregory Y.H. Lip, Cécile Laroche, Mircea I. Popescu, Lars H. Rasmussen, Laura Vitali‐Serdoz, Gheorghe‐Andrei Dan, Zbigniew Kalarus, Harry J.G.M. Crijns, Mario M. Oliveira, Luigi Tavazzi, Aldo P. Maggioni, Giuseppe Boriani
Journal: European Journal of Heart Failure (2015)
Influence of complete resection of residual disease in responding patients to imatinib (IM) on the outcome of pts with advanced GIST: The experience of the BFR14 trial of the French Sarcoma Group
Authors: E. Stoeckle, P. Meeus, M. Rios, F. Duffaud, F. Bertucci, A. Adenis, S. Chabaud, J. Y. Blay, A. Le Cesne, S. Bonvalot
Journal: Journal of Clinical Oncology (2008)

10549 Background: Since our previous reports (JYB JCO07, ALC ASCO07) IM is given continuously without treatment interruption until disease progression (PD) or intolerance as the first-line targeted therapy for advanced GIST. The impact of resection of residual disease in responding patients (pts) on progression-free survival (PFS) remains controversial. Methods: Since June 2002, 378 pts have been included in the BFR14 trial which compared continuous IM with interrupted (INT) IM beyond 1 and 3 yrs of treatment in pts with advanced GIST. Thirty-six pts (9%) underwent rescue surgery (RS) of residual masses after initiation of IM. IM was reintroduced in all pts after surgery. Their characteristics and outcome were compared to the entire cohort of pts, with the exception of pts randomized in the INT arms (at 1 and 3 yrs). Responding pts to IM operated during the first year of treatment were compared to 237 patients without progression at one year. Results: Before RS 16 pts were in objective response, 9 in stable disease (SD) and 10 in PD (1 NE pt) during IM therapy. A R0/R1 resection was performed in 25 pts and a R2 resection in 6 pts (R unknown in 5 pts) after a median time of 8 months from inclusion. There was no difference between the 2 groups of pts but pts with RS were more likely (p= 0.004) not having been primarily resected for their primaries. After a median follow-up of 21 months, the PFS and OS of these 36 pts and the rest of the population were similar. After surgery, recurrences occurred in 5/25 of patients with SD-PR-CR under IM, but in 10/10 pts with tumor progression. The PFS at 2 yrs were 93% for pts who underwent an R0/R1 resection in responding pts, 45% for pts with a R2 resection and 50% for the group of non operated pts. Conclusions: Surgical R0/R1 resection of residual disease in responding pts to IM highly selected a favorable group of pts with a prolonged PFS. This work is supported by research funding from Novartis Pharma. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Glaxo, Novartis, Pfizer, PharmaMar, Roche Amgen, Glaxo, Novartis, Pfizer, PharmaMar, Roche Novartis, Pfizer Novartis, Pfizer, sanofi-avantis
A comparison of mortality between patients treated with hemodialysis and peritoneal dialysis.
Authors: W E Bloembergen, F K Port, E A Mauger, R A Wolfe
Journal: Journal of the American Society of Nephrology (1995)

Patients with ESRD treated with dialysis have a high mortality rate. Controversy exists as to whether this high mortality rate is affected by modality choice. The purpose of this epidemiologic study was to compare mortality in prevalent hemodialysis-treated (HD) and peritoneal dialysis-treated (PD) patients in a large national sample, adjusting for demographic characteristics. Data were obtained from the U.S. Renal Data System for patients prevalent on January 1 of the years 1987, 1988, and 1989, each with 1 yr of follow-up. Patients were censored at transplantation. Death rates per 100 patient years were compared between HD and PD, adjusting for age, race, gender, cause of ESRD (diabetes versus nondiabetes) and < 1 yr or > 1 yr of prior ESRD, by the use of Poisson regression. There were 42,372 deaths occurring over 170,700 patient years at risk. On average, prevalent patients treated with PD had a 19% higher adjusted mortality risk (relative risk (RR) = 1.19; P < 0.001) than did those treated with HD. This risk was found to be insignificant (P > 0.05) and small for ages < 55 and increasingly large and significant for ages > 55 yr. It was accentuated in diabetics (RR = 1.38; P < 0.001) but was also present in nondiabetics (RR = 1.11; P < 0.001). Although present in both males and females, this risk was accentuated in females (RR = 1.30 versus 1.11; both P < 0.001). In this national study of prevalent U.S. dialysis patients, treatment assignment to PD was associated with a 19% higher all-cause mortality rate than HD.(ABSTRACT TRUNCATED AT 250 WORDS)
Defining dysbiosis threatens Koch's postulates and current dogma on the role of Paneth cells in Crohn's disease
Authors: Mathias Chamaillard, Katarina Radulovic
Journal: Gut (2015)

Whereas the intestinal epithelium self-renews every 3–5 days, it promotes a robust antimicrobial response to enteropathogens when they first breach the integrity of the mucosal barrier. Foremost, the interaction between gut commensals and the single layer of intestinal epithelial cells is involved in many common, essential physiological processes (eg, nutrient absorption, cell proliferation, cell motility and metabolic activities). In Crohn's disease, it is thought that impaired epithelial function develops into transmural inflammatory lesions at the terminal ileum, where abnormal granule formation and enhanced necroptosis of Paneth cells are frequently observed. Located at the base of the crypt of Lieberkuhn in the small intestine, Paneth cells are one of the four major epithelial cell lineages, which play an essential role in maintaining the resistance of epithelial surfaces to microbial colonisation. Accordingly, genome-wide association studies have revealed a large set of inborn genetic errors in several regulatory factors involved in the maintenance of Paneth cell function.1 However, it is still not clear whether impaired secretory function of Paneth cell precedes the onset and relapse of Crohn's disease. In this context, it is essential to gain an understanding of the exact …
Low Dose Botulinum Toxin in Spasmodic Torticollis
Authors: D F D'Costa, R J Abbott
Journal: Journal of the Royal Society of Medicine (1991)

Botulinum toxin has been successfully used to treat spasmodic torticollis. The optimum dosage is not clear and the recommended doses in the United Kingdom are 20-25 ng. We have used much lower doses (average 13 ng) without loss of efficacy and accompanied by a reduction in side effects. We treated 12 patients (eight women and four men) with a mean duration of torticollis of 4 years. Eleven of the 12 patients (91%) showed an improvement in total scores for pain and degree of head movement. The benefits appeared a week after treatment and lasted for 3 months. Side effects were minimal and transient. Our experience suggests low doses of the toxin may be equally efficacious.
Clinical characteristics of hospitalized psychotic patients who refuse antipsychotic drug therapy
Authors: J M Zito, W W Routt, J E Mitchell, J L Roerig
Journal: American Journal of Psychiatry (1985)

Thirty psychotic patients who refused antipsychotic medication were compared with 30 patients matched for age, sex, treatment ward, commitment status, and diagnosis who consented to drug treatment. Refusers were no more assaultive or combative than consenters; they were less often diagnosed as having schizophrenia and more often diagnosed as having bipolar or schizoaffective illness. A comparison between 17 of the least symptomatic refusers and 17 of the most persistent refusers showed that persistent refusers were more likely to have a diagnosis of schizophrenia; least symptomatic refusers were more often diagnosed as having affective disorders or schizoaffective disorders.
Genetic variations in the TLR signaling pathway are associated with childhood asthma
Authors: Ramesh Chandra Pandey, Sven Michel, Riccardina Tesse, Aristea Binia, Michaela Schedel, Liming Liang, Norman Klopp, Erika von Mutius, Andrea von Berg, Albrecht Bufe, Ernst Rietschel, Andrea Heinzmann, Otto Laub, Burkhard Simma, Thomas Frischer, Jon Genuneit, Thomas Illig, Michael Kabesch
Journal: European Respiratory Journal (2012)

Background: Common single nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs) are associated with asthma and atopy, but very little is known about the relevance of SNPs in TLR regulatory and downstream signaling pathway molecules.

Objective: To systematically analyze the association between SNPs in TLR signaling pathway genes and childhood asthma and atopy.

Methods: Common SNPs present in TLR signaling pathway were retrieved from HapMap database and LD analyses were performed to determine tagging SNPs. Association of 375 tagging SNPs with asthma were analysed in a genome wide association (GWA) dataset consisting of 651 asthmatics and 652 controls. SNPs were genotyped by Illumina HumanHap300Chip (n=169) or MALDI-TOF MS (n=19) or imputed (n=187). Algorithms were applied to rank associations and clustering of the associated genes on a virtual pathway map was performed by a systems biology approach and we assessed the putative functional relevance of associated SNPs by in silico analysis.

Results: We identified 41 genes involved in the TLR signaling and regulatory pathways, harbouring 1405 SNPs (tagged by 375) with minor allele frequency >5% in the HapMap (CEU) population. SNPs located in 19 genes showed association with asthma at a significance level of at least p<0.05. Top ranked asthma-associated genes (e.g. IRAK-1, MKK-3, and ERK-2) mapped to distinct functional clusters within the TLR pathway and associated SNPs were located in promoter (n=16), intronic (n=116) and downstream regions (n=16).

Conclusion: SNPs in TLR signaling network genes show association with asthma and distinct clusters are associated with atopic and non-atopic asthma.
STUDIES OF HUMAN ANTI-γ-GLOBULIN FACTORS REACTING WITH PEPSIN-DIGESTED γ-GLOBULINS
Authors: Thomas G. Lawrence, Ralph C. Williams
Journal: The Journal of Experimental Medicine (1967)

Many sera from normal individuals as well as patients with various disease states contain agglutinating antibodies which show specificity for antigenic determinants of gamma-globulin revealed by pepsin digestion at pH 4.1. Sera containing such agglutinating activity as well as sera negative for these agglutinators contain low molecular weight (3S-5S) components of slow gamma-mobility which inhibit these agglutination reactions. Low molecular weight inhibitors show both auto- and isospecificity, and are antigenically related to the 5S pepsin fragment of gamma-globulin. A common situation is thereby revealed in which human anti-gamma-globulin antibodies showing specificity for pepsin-digested gamma-globulins are present in serum along with low molecular weight gamma-globulin components capable of inhibition. Autoreactivity or autospecificity of such anti-gamma-globulin factors is a phenomenon shared by both normal human sera and sera from patients with various disease states.
Intracellular ESAT-6: A new biomarker of mycobacterium tuberculosis infection?
Authors: Nikolaos Poulakis, Angelos Gritzapis, Vassilis Tsilivakos, Maria Ploussi, Michail Leventopoulos, Chrysovalantis Papageorgiou, Andreas Anastasopoulos, Simona Karabela, Evangelos Vogiatzakis, Pantelis Constantoulakis
Journal: European Respiratory Journal (2013)

Introduction: Early secreted antigenic target 6 (ESAT-6) is a virulent factor of  Mycobacterium tuberculosis  (M.TB.) infection. Thus, the identification of intracellular (i/c) ESAT-6 antigen in host cells would be a direct marker of TB infection. Recently, we have developped a method to detect i/cESAT-6 by flow cytometry.  The aim of this study is to investigate the expression of i/c ESAT-6 in the host cells of individuals with TB infection.  Methods: The expression of i/cESAT-6 was examined in the blood of 41 active TB patients, in 33 close contacts with an index TB case and in 43 medically immunosuppressed patients under treatment with biological agents. Furthermore, i/cESAT-6 was tested in the sputum smear of 12 active TB patients.  Results: The i/c ESAT-6 was positively detected in the blood of 90% of active TB patients, in 57% of close contacts and in 49% of immunosuppressed patients. In the 12 culture positive TB sputum specimens, sputum smear was Ziehl-Nielsen positive in 8 out of 12 and negative in 4 out of 12, while i/cESAT-6 in sputum cells was detected in all cases.  Conclusion: In this study we showed that i/cESAT-6 is detected in the peripheral blood mononuclear cells and in sputum cells of individuals with TB infection. As this is a direct marker of M.TB. infection, further studies are needed in order to define exactly its diagnostic performance in TB infection and its discriminatory capacity between immunological memory and true infection.
Celebrating the ACP Centennial: From the <i>Annals</i> Archive—Breast Cancer Screening
Authors: Deborah Cotton
Journal: Annals of Internal Medicine (2015)

Editorials19 May 2015Celebrating the ACP Centennial: From the Annals Archive—Breast Cancer ScreeningDeborah Cotton, MD, MPH, Deputy EditorDeborah Cotton, MD, MPH, Deputy EditorSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M15-0183 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail During the 2015 centennial year of the American College of Physicians, publisher of Annals of Internal Medicine, Annals editors will link an article in each issue with an earlier paper from our archives addressing the same disease or clinical question. We hope our readers find this interesting and we welcome comments, especially from physicians who were practicing at the time of publication of the original paper who might offer insight into the impact of the earlier paper on their knowledge or practice.Breast cancer screening is a contentious issue. In this issue, Kerlikowske and colleagues (1) address the most recent ...References1. Kerlikowske K, Zhu W, Tosteson ANA, Sprague BL, Tice JA, Lehman CD, et al; Breast Cancer Surveillance Consortium. Identifying women with dense breasts at high risk for interval cancer. A cohort study. Ann Intern Med. 2015;162:673-81. doi:10.7326/M14-1465 LinkGoogle Scholar2. Lerner BH. Fighting the war on breast cancer: debates over early detection, 1945 to the present. Ann Intern Med. 1998;129:74-8. doi:10.7326/0003-4819-129-1-199807010-00028 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoFighting the War on Breast Cancer: Debates over Early Detection, 1945 to the Present Barron H. Lerner Identifying Women With Dense Breasts at High Risk for Interval Cancer Karla Kerlikowske , Weiwei Zhu , Anna N.A. Tosteson , Brian L. Sprague , Jeffrey A. Tice , Constance D. Lehman , Diana L. Miglioretti , and Identifying Women With Dense Breasts at High Risk for Interval Cancer Karla Kerlikowske , Weiwei Zhu , Anna N.A. Tosteson , Brian L. Sprague , Jeffrey A. Tice , Constance D. Lehman , Diana L. Miglioretti , and Metrics 19 May 2015Volume 162, Issue 10Page: 728KeywordsArchivesArmed forcesBreast cancerBreast cancer screeningCancer screeningGenetic testingMammography ePublished: 19 May 2015 Issue Published: 19 May 2015 CopyrightCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Effect of low level light therapy (LLLT) on an experimental model of LPS-induced lung inflammation
Authors: Ana Paula Ligeiro de Oliveira, Rodolfo de Paula Vieira, Jean Pierre Schatzmann Peron, Eliane Gomes, Flavia Mafra de Lima, Momtchilo Russo, Flavio Aimbire
Journal: European Respiratory Journal (2012)

Acute lung injury (ALI) induced by lipopolysaccharide (LPS) exposure is characterized by cellular infiltrate, edema and altered airway responsiveness. Traditional treatments for ALI include strategies of mechanical ventilation and a variety of drugs such as, corticosteroids and other disease-modifying agents. However these conventional therapies may cause important side-effects that compromise long term therapies. In this sense, Low Level Light Therapy (LLLT) have already demonstrated primising data in reducing airway inflammation. Thus, in the present study we investigated the ability of LLLT to modulate neutrophil infiltration to the lungs. For that, Balb/c mice were submitted to daily dosis of 10 mg of LPS for 3 consecutive days. LLLT group were submitted to irradiation daily at 2, 4 and 6 hours after LPS. Controled groups received PBS and were or not irradiated. On day 4, 24 hours after LPS exposure animals were sacrificed and LBA cellularity, cytokine secretion and airway reactivity by FlexiVent were analysed. Our results demonstrate a significant decrease in total cells and neutrophils recovered from the bronchoalveolar lavage (BAL) of LPS-treated animals after LLLT. We also detected reduced amounts of IL-6 but not IL-17 after LLLT. Airway reactivity to metacholine (Mch) also reduced. In conclusion, our data reveals a promising role for LLLT as an alternative therapeutic approach for acute lung inflammation.