tbuckley/cabot-search huggingface dataset:
Activation of Syk in Peripheral Blood B Cells in Patients With Rheumatoid Arthritis: A Potential Target for Abatacept Therapy
Authors: Shigeru Iwata, Shingo Nakayamada, Shunsuke Fukuyo, Satoshi Kubo, Naoki Yunoue, Sheau‐Pey Wang, Maiko Yoshikawa, Kazuyoshi Saito, Yoshiya Tanaka
Journal: Arthritis & Rheumatology (2014)

Objective B cells play a pivotal role in the pathogenesis of autoimmune diseases. Although Syk functions as a key molecule in B cell receptor signaling, the pathologic role of Syk in B cells in rheumatoid arthritis (RA) remains unclear. The purpose of this study was to assess the relevance of activation of Syk in B cells to the pathologic development of RA and to the responsiveness of RA patients to treatment with biologics. Methods Healthy subjects (n = 36) and patients with moderate or severe RA disease activity (n = 70) were studied. The phosphorylation of Syk (pSyk) in peripheral blood B cells was measured by flow cytometry, and its correlation with clinical characteristics and changes after administration of biologic agents was evaluated. Results Levels of pSyk in peripheral blood B cells were preferentially higher in patients with RA compared to healthy subjects. Patients with significantly higher pSyk levels were strongly positive for anti–citrullinated protein antibodies (ACPAs). High pSyk levels were not correlated with the severity of disease activity. Treatment with abatacept, but not tumor necrosis factor inhibitors, significantly reduced the levels of pSyk in RA peripheral blood B cells. Abatacept also significantly reduced the proportion of follicular helper T (Tfh) cells. Conclusion Levels of pSyk in peripheral blood B cells were significantly elevated in patients with RA, and these patients also exhibited strong positivity for ACPAs. These data suggest that abatacept seems to inhibit the phosphorylation of Syk in B cells, as well as the development of Tfh cells, thus highlighting the relevance of B cell–T cell interactions as a potential target of abatacept therapy in RA.
MPs call for overhaul of dentists' pay
Authors: Zosia Kmietowicz
Journal: BMJ (2001)

The current system used to pay dentists in the United Kingdom should be overhauled to allow the public better access to dental care and to encourage dentists to adopt more preventive treatment strategies, a report from the House of Commons health select committee has said.

Too little is being done to prevent dentists leaving the NHS in droves, claimed the report, the …
Arthritis and Allied Conditions: A Textbook of Rheumatology.
Authors: William J. Koopman
Journal: Annals of Internal Medicine (1991)

Introduction to the study of rheumatic diseases scientific basis for the study of the rheumatic diseases clinical pharmacology of anti-rheumatic drugs rheumatoid arthritis other inflammatory arthritic syndromes systematic rheumatic diseases miscellaneous rheumatic diseases regional disorders of joints and related structures osteoarthritis metabolic bone and joint diseases infectious arthritis.
mTOR inhibition blocks tumor growth and pleural fluid accumulation in experimental murine mesothelioma
Authors: Marialena Vazakidou, Sophia Magouta, Charis Moschos, Magda Stratiki, Charis Roussos, Ioannis Kalomenidis
Journal: European Respiratory Journal (2011)

mTOR is up-regulated in malignant mesothelioma. We aimed to evaluate the effect of Temsirolimus, an mTOR inhibitor, in in vivo models of the disease.  AE17 and AB1 murine mesothelioma cells were injected into the right flank of syngeneic mice (C57BL/6 and BALB-c, respectively) to create subcutaneous tumors. C57BL/6 mice were injected intrapleurally with AE17 cells to create pleural tumors and effusions. Animals were treated with Temsirolimus (20mg/kg) or vehicle, 5 days/week starting when tumors become palpable (flank model) or on days 2-6, 9-15 following the intrapleural injection of tumor cells (pleural model).  Among mice with AE17 flank tumors, the mean ±SEM tumor volume at day 26 was 1261±383mm 3  in control and 383±86mm 3  in treated animals (p 3  in control and 174±76 mm 3  in treated animals (p=0.026). Among mice with pleural AE17 tumors, the mean ±SEM pleural fluid volume at day 15 was 532±119microL in control and 240±44microL in treated animals (p=0.018). The mean ±SEM pleural tumor weight was 739±72mg in control and 256±10mg in treated animals (p  Inhibition of mTOR substantially reduced syngeneic mesothelioma growth blocked pleural fluid accumulation in animals bearing mesothelioma tumors.
Royal Medical and Chirurgical Society: Tuesday, July 6, 1841
Authors: None Williams
Journal: BMJ (1841)

ROYAL MEDWOAL £ UIU1CEL -OCTETY.tion of such measures without sufficient notice, and at the ame-time to dcourage their adoption withouIt suflfcient time having been afforded for reflection when they are introduced.The passing of any measure likely to affect materially the in- terests of the Association, will not be hastily acceded to by a general nmeeting, if, by postponing it for a timne, it is likely that the Association will derive the advantage of ascertaining the views of the members at large.By the arrangements now adopted, this is readily accomplished in regard to all matters brought forward by the council.The proposed report is always circulated amongst all the memjbers of the council, and consequently in every place where the association possesses influence, and the branches have thus the oppor- tunity afforded them of expressing their opinion on the questions intended to be brought forward at the general meeting.If this provision be called for and acted upon with respect to measures, the bearing of which has been well considered by those who are most intimately acquainted with the affairs of the association, it becomes far more necessary in respect to such as may be brought forward without having previously received the advantage of such consideration.The giving efficiency and support to those branch associations which already exist, and encouragement to the formation of new ones, wherever a sufficient number of members reside, should,therefore, as it appears to us, occupy the attention of the council.In many other respects,-for instance, in affording occasions to bring the members of the profession into friendly intercourse with each other, in facili- tating the collecting and communication of valu- able local information, in conducing to the rubbing off the rust of seclusion so apt to be acquired by those wvho are thrown entirely upon their own resources, these more local institutions can scarcely be too highly appreciated.
Abstract 13474: Incremental Value of Left Atrial Conduction Time for Predicting Atrial Fibrillation in Patients Receiving Cardiac Pacing
Authors: Makoto Saito, Kazuaki Negishi, Wojciech Kosmala, Gerry Kaye, Thomas H Marwick
Journal: Circulation (2014)

Background: Atrial fibrillation (AF) is a relatively common complication of cardiac pacing. Prolonged LA electromechanical conduction time (EMT) has been proposed for prediction of new- onset AF. We sought to investigate the incremental benefit of EMT for predicting AF over conventional predictors in pts undergoing pacing. Methods: We prospectively followed 127 pts with preserved ejection fraction, absence of chronic or known paroxismal AF, and a pacemaker implantation because of atrioventricular block in the PROTECT-PACE trial for 2 years. Reliable recognition of AF episodes was based on pacemaker monitoring. Echocardiography was performed just after the implantation. EMT was measured as the time interval from the onset of the P wave to the peak of the late diastolic wave from the septal and lateral mitral annulus on tissue Doppler echocardiography. We also assessed LA volume index (LAVI) and CHADS2 score. Results: 24 patients (19%) had new onset AF. Septal EMT was significantly longer in pts with AF than that in pts without AF (130±31 vs 112±31 ms, p=0.01). Larger LAVI and prolonged septal EMT were significantly associated with AF. In sequential logisitic models, LAVI added to the model power of CHADS2 score, and the model based on CHADS2 score and LAVI was significantly improved by adding septal EMT (Figure). Conclusion: EMT provides incremental value over the conventional risks for predicting a first episode of AF in patients receiving cardiac pacing.
Immunofluorescent patterns in the skin in Besnier's prurigo.
Authors: GILLIAN I. HODGKINSON, JOHN D. EVERALL, HUW V. SMITH
Journal: British Journal of Dermatology (1977)

The immunofluorescent patterns in the skin of eighteen patients with Besnier's prurigo were studied at different stages of eczematous lesions. The presence, distribution pattern, and numbers of immunoglobulin and complement-positive lymphocytes in twenty-nine biopsies are reported. In all cases IgE-positive lymphocytes were present in both clinically uninvolved and involved skin. IgG, IgM and IgE-positive lymphocytes showed a characteristic distribution pattern in the dermis. In the acute stages IgM deposition was prominent in the basement membrane zone and it is suggested that damage to the basement membrane results in diffusion of immunoglobulin and complement into the epidermis. These features were not present in a control group of normal skin and of other dermatoses.
Cardiac hemodynamic in obstructive sleep apnea and overlap syndrome
Authors: Ksenia Nazarenko, Marina Polianskaja, Inna Zvol, Svetlana Moskalenko
Journal: European Respiratory Journal (2014)

A large number of studies proved the relationship between the obstructive sleep apnea (OSA) and cardiovascular diseases, but cardiovascular pathology in patients with OSA in combination with COPD (overlap syndrome (OS)) studied less.  Aim: To study cardiac hemodynamic in patients with OSA and OS.  Material and methods: 50 patients with excessive daytime sleepiness and OSA (polysomnography), age 47,12±2,16 years, 54 patients with OS (Post BD FEV1/FVC (58,57±2,03)%, FEV1 (66,71±3,14)%), age 57,85±1,36 years and 10 healthy subjects(age 54,1±4,31years).  Left ventricular hypertrophy (LVH)  was defined by left ventricular mass index (LVMI) ( male  > 115  g  /  m  ² , female>95  g  /  m  ² ) (echo-Doppler  ultrasound  scanning examination).  Results. In OSA group LVMI was 10% higher vs healthy subjects (p  In OS group LVMI was 23% higher vs healthy subjects (p  In OS group LVMI and IVRT were 14 and 10% higher than in OSA group (p  LVH and diastolic dysfunction were detected in 44% and 36% patients with OSA respectively.   In OS group  LVH and diastolic dysfunction were detected in 41% and 37%.  Conclusions. Our results demonstrate high prevalence of LVH and diastolic dysfunction in patients with OSA. COPD negatively affected the LVH and diastolic function in patients with OSA.
Screening for Hepatitis C
Authors: Charlie M. Wray, Andrew M. Davis
Journal: JAMA (2015)

of the Clinical Problem Hepatitis C virus affects an estimated 180 million people worldwide,making it themost common chronic blood-borne pathogen.1 Less than half of infected individuals clear their infection without treatment, and 15% to 40% of patients with HCV progress to cirrhosisorhepatocellular cancer.HepatitisCvirus infection is themost commonindication for liver transplantationand is thecauseof8000 to 13 000 deaths in the United States each year.2 SinceHCV testingofbloodproductswas implemented in 1992, the2most important risk factors forHCVacquisitionarepastor current injection drug use and birth between 1945 and 1965.3 DetectionofHCV infectionhasprovendifficultbecausebehavioral riskhistories are often incomplete, most newly infected individuals have no ormild nonspecific symptoms, and up to 50%of those infected have persistently normal serum transaminase values. Not surprisingly, 45% to85%of all personswith chronicHCV infection are unaware that they are infected.3When patients are identified and receive proper HCV treatment, they can reduce their risk of hepatocellular cancer by 70% and all-cause mortality by 50%.3
Targeting tumor-associated macrophages: A novel strategy against breast cancer.
Authors: Yunping Luo, He Zhou, Joerg A. Krueger, Charles D. Kaplan, Carrie Dolman, Dorothy Markowitz, Wenyuan Wu, Cheng Liu, Ralph A. Reisfeld, Rong Xiang
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5562 

Tumor development and progression are strongly linked to inflammation and the presence of tumor-associated macrophages (TAMs). Thus, antitumor activity can be achieved by targeting TAM recruitment, activation and extracellular matrix interactions. TAMs consist primarily of a polarized M2 (CD206+, F4/80+) macrophage population with little cytotoxicity for tumor cells and poor antigen presenting capacity. Legumain, a member of the asparaginyl endopeptidase family, functioning as a stress protein, was found highly up-regulated on TAMs in many murine and human tumor tissues, but absent or only present at very low levels in all normal tissues and on circulating macrophages of M1 phenotype. Here, we demonstrate for the first time that the intense orverexpression of Legumain on TAMs provides for a unique and novel approach to tumor therapy. In fact, immunization against Legumain dramatically reduced the density of TAMs in tumor tissues, resulting in a decrease of pro-angiogenesis as well as tumor growth factors released by these macrophages. This, in turn, decisively suppressed tumor angiogenesis and tumor growth and metastasis. Importantly, we demonstrated the success of this anti-TAM strategy in three different murine tumor models, in either prophylactic or therapeutic settings. In conclusion, reducing the density of TAMs in the tumor stroma sufficiently remodeled the tumor microenvironment and allowed to gain further insights into mechanisms required for an effective intervention in tumor growth and metastasis that may ultimately lead to better anticancer strategies.
Asylum seekers and refugees in Britain: Health needs of asylum seekers and refugees
Authors: A. Burnett
Journal: BMJ (2001)

This is the second in a series of three articles 

People who are seeking asylum are not a homogeneous population. Coming from different countries and cultures, they have had, in their own and other countries, a wide range of experiences that may affect their health and nutritional state. In the United Kingdom they face the effects of poverty, dependence, and lack of cohesive social support.1 All these factors undermine both physical and mental health. Additionally, racial discrimination can result in inequalities in health and have an impact on opportunities in and quality of life.2

Refugees' experiences also shape their acceptance and expectations of health care in the United Kingdom.3 Those from countries with no well developed primary healthcare system may expect hospital referral for conditions that in Britain are treated in primary care. This can lead to disappointment for refugees and irritation for health workers, who may also feel overwhelmed by the many and varying needs of asylum seekers, some of which are non-medical but nevertheless affect health. Addressing even a few of these needs may be of considerable benefit.

Previous studies in the United Kingdom have found that one in six refugees has a physical health problem severe enough to affect their life and two thirds have experienced anxiety or depression. 4 5 Disentangling the web of history, symptoms—which may be minimised or exaggerated for a range of reasons—and current coping mechanisms requires patience and often several sessions. Medication should be as simple as possible.

#### Summary points

Asylum seekers and refugees are not a homogeneous group of people, and have differing experiences and expectations of health and of health care

Symptoms of psychological distress are common, but do not necessarily signify mental illness

Trained interpreters or advocates, rather than family members or friends, should be used wherever possible …
MAGNESIUM SULFATE IN PAROXYSMAL TACHYCARDIA
Authors: W T ZIMDAHL
Journal: Annals of Internal Medicine (1946)

Case Reports1 September 1946MAGNESIUM SULFATE IN PAROXYSMAL TACHYCARDIAWALTER T. ZIMDAHL, B.A., M.D.WALTER T. ZIMDAHL, B.A., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-25-3-531 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIt has long been known that the magnesium ions act as a depressant to cardiac musculature. Smith, Winkler, and Hoff1reported bradycardia, conduction disturbances and eventually cardiac arrest with high concentration resulting from parenteral administration. However, it was not until Boyd and Scherf2reported their series of cases that the therapeutic effect and beneficial results of magnesium salts in paroxysmal tachycardia were generally recognized. The effect of intravenous injections of magnesium sulfate in 10 cases of paroxysmal tachycardia and one case of flutter was studied. They found that the injection of a 10 per cent solution was beneficial in three...Bibliography1. SMITHWINKLERHOFF PKAWHF: Electrocardiographic changes and concentration of magnesium serum following intravenous injection of magnesium salts, Am. Jr. Physiol., 1939, cxxvi, 720-730. CrossrefGoogle Scholar2. BOYDSCHERF LJD: Magnesium sulfate in paroxysmal tachycardia, Am. Jr. Med. Sci., 1943, ccvi, 43. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Providence R. I.*Received for publication June 22, 1945.From the Heart Station of the Rhode Island Hospital, Providence, Rhode Island.†Former Resident Physician, Heart Station of the Rhode Island Hospital. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHypo- und Hypermagnesämie aus kardiologischer SichtCurrent status of treatment of paroxysmal atrial tachycardiaTherapie der HerzinsuffizienzMineralstoffwechsel und KreislaufMineralstoffwechsel und KreislaufAccidental digitoxin poisoning in childrenPAROXYSMAL AURICULAR TACHYCARDIA: OBSERVATIONS IN 47 CASES*GEORGE M. JONES, M.D., F.A.C.P.Digitalis Poisoning and Its TreatmentUse of pronestyl in the treatment of ectopic rhythmsThe effects of magnesium upon cardiac arrhythmiasMeasures Used in the Prevention and Treatment of Cardiac Arrhythmias 1 September 1946Volume 25, Issue 3Page: 531-533KeywordsAttentionBradycardiaHeartIntravenous injectionsMagnesiumSaltsSulfatesTachycardia Issue Published: 1 September 1946 PDF downloadLoading ...
Abstract 12307: Atrial Fibrillation is a Strong Risk Factor for Adverse Cardiovascular Outcomes in Patients With Implantable Cardioverter-Defibrillators
Authors: Ian C Chang, Erin Austin, Wayne O Adkisson, Henri Roukoz, Lisa N von Wald, Scott Sakaguchi, David G Benditt, Lin Y Chen
Journal: Circulation (2014)

Purpose: The use of implantable cardioverter-defibrillator (ICD) continues to increase. Our knowledge of predictors of adverse cardiovascular (CV) outcomes in patients with ICDs is mostly derived from clinical trials. This hospital-based retrospective cohort study aims to identify predictors of adverse CV outcomes in patients with ICD in a real-world setting.

Methods: We identified consecutive patients who had ICD implantation at the University of Minnesota Medical Center between Jan 1, 2008 and Dec 31, 2009. Baseline data on demographics, CV risk factors and diagnoses, and medications were collected from charts. The follow-up was through Dec 31, 2012. Our primary outcome is a composite CV outcome (table). We used multivariable Cox proportional hazards model and a stepwise selection method to fit the most parsimonious model to predict the composite outcome.

Results: We included 166 patients [mean age (SD), 60 (15) years; 74% male]; 64 (38.8%) patients had diabetes (DM) and 140 (84.3%) were on beta-blockers (BB) at baseline. The ICD was placed in 119 (71.7%) patients for primary prevention and 47 (28.3%) for secondary prevention of sudden cardiac death. There were 98 patients (59.0%) with the composite outcome and 25 (15.1%) with incident or recurrent atrial fibrillation (AF). The median follow-up was 633 days. The full model included age, sex, coronary artery disease, DM, hypertension, LV ejection fraction, use of BB, anticoagulants, estimated GFR, and incident or recurrent AF. The table shows the most parsimonious model for prediction of the composite outcome.

Conclusions: In patients with ICDs, the presence of AF is significantly associated with a 5-fold increased risk of adverse CV outcomes while the use of BB is associated with lower risk. Our study suggests that AF is a strong risk factor for adverse CV outcomes in patients with ICDs. Further research is warranted to determine whether maintaining sinus rhythm in patients with AF and ICD would lead to improved outcomes.

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LIVER ABSCESS DUE TO CLOSTRIDIUM PERFRINGENS
Authors: R M KIVEL, A KESSLER, D J CAMERON
Journal: Annals of Internal Medicine (1958)

ExcerptINTRODUCTIONAlthough clostridia are widely distributed in nature and are normal inhabitants of the human intestine, their invasiveness as pathogens is usually related to some sort of physical trauma with local tissue destruction. Clostridia, however, may often be present at the site of accidental or surgical trauma without causing clinical infection. This close association of clostridial infection with trauma, together with the rarity of other clinical types of infection, has been considered as evidence that some peculiar host factors, usually presumed to be necrotic tissue without oxygen supply, are required for initiation of infection by these organisms.The present report...
Abstract #LB-301: Whole mitochondrial genome DNA mutation analysis on NCI-60 human cancer cell line panel
Authors: Grant Wu, Benjamin Legendre, Sandra Gunselman, Manika Koul, Eric Kaldjian
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Mitochondria are central to cellular energy metabolism, free radical generation and apoptosis. Mutations in mitochondrial DNA (mtDNA) result in defects of normal mitochondrial function and are hypothesized to participate in the induction and development of cancer. Numerous mtDNA mutations have been reported and linked to different cancer types. The NCI-60 cancer cell line panel has been extensively used for pharmacological studies of anti-cancer agents, and has been characterized at the molecular level. In collaboration with the NCI, we have produced the first mtDNA sequence analysis of the cell lines in order to elucidate their mutation and polymorphism profiles. These profiles will be useful in determining potential diagnostic and therapeutic biomarkers. The NCI-60 panel consists of 59 human cancer cell lines derived from 9 types of tumors: lung, colon, breast, ovarian, leukemia, renal, melanoma, prostate and brain and were provided by the Developmental Therapeutics Program at the National Cancer Institute. Forty overlapping amplicons covering the entire mtDNA genome were direct sequenced on an ABI 3730 sequencer for each of the NCI-60 cell lines. The highest average mutation rate was observed in the leukemia cell lines suggesting that mtDNA function/dysfunction may play a more important role in the development and progression in this type of cancer as compared to other solid tumors. In general, we also observed many small insertions, deletions and single base changes in the mtDNA genome. Further analysis of our data may produce more evidence of a link between the mitochondria and cancer. These data may provide further insight into early disease states and may also aid in the development of better cancer diagnostics by identifying useful biomarkers as well as determining treatment choices.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-301.