tbuckley/cabot-search huggingface dataset:
Antibodies to Endothelial Cell Growth Factor and Obliterative Microvascular Lesions in the Synovium of Patients With Antibiotic‐Refractory Lyme Arthritis
Authors: Diana Londoño, Diego Cadavid, Elise E. Drouin, Klemen Strle, Gail McHugh, John M. Aversa, Allen C. Steere
Journal: Arthritis & Rheumatology (2014)

Endothelial cell growth factor (ECGF) was recently identified as the first autoantigen known to be a target of T cell and B cell responses in ~20% of patients with antibiotic-refractory Lyme arthritis. The goal of the current study was to look for a pathologic correlate between ECGF autoantibody responses and histologic findings in synovial tissue.Synovial tissue was examined from 14 patients with antibiotic-refractory Lyme arthritis and 6 patients with other forms of chronic inflammatory arthritis, primarily rheumatoid arthritis. The tissue sections were subjected to chemical and immunostaining, and IgG antibody responses to ECGF were determined by enzyme-linked immunosorbent assay (ELISA). Each finding was ranked for statistical analysis.In each disease, synovial tissue showed synovial hypertrophy, vascular proliferation, immune cell infiltrates, and fibrosis. However, among the 14 patients with antibiotic-refractory arthritis, 8 (57%) had obliterative microvascular lesions in the tissue, compared with none of the 6 patients with other forms of chronic inflammatory arthritis (P = 0.04). Among the patients with Lyme arthritis, 5 (36%) had autoantibody responses to ECGF, and all 5 had obliterative lesions, as compared with only 3 of 9 patients who lacked ECGF antibody responses (P = 0.009). Moreover, the magnitude of ECGF antibody responses correlated directly with the extent of obliterative lesions (P = 0.02) and with greater vascularity in the tissue (P = 0.05).The correlations of ECGF autoantibody reactivity with obliterative microvascular lesions imply that these autoantibodies may be involved in the obliterative process, suggesting that anti-ECGF antibodies have specific pathologic consequences in the synovial tissue of patients with antibiotic-refractory Lyme arthritis.
The CF-ABLE score: A 2-year evaluation of a 4-year prognostic tool
Authors: Johan Meurling, Cormac McCarthy, Cedric Gunaratnam, Noel Gerry McElvaney
Journal: European Respiratory Journal (2014)

The CF-ABLE score was developed over two years ago in Beaumont Hospital as a prognostic tool for cystic fibrosis (CF). The score ranges from 0 to 7, based on age, body mass index (BMI), lung function and number of exacerbations in the last three months. Patients with a score of >5 points have a 26% risk of poor outcome within four years1. Now after incorporating the score clinically for two years we can start evaluating its clinical application.

103 charts were reviewed in the Beaumont Hospital CF unit. 25 were excluded due to incomplete data. 77 patients were evaluated for lung transplant referral, transplantation and death in subcategories of ABLE scores above or below 5.

25 patients had an ABLE score >5 in 2011. Six died over the following two years, seven were referred for lung transplant, and four more received transplants. Out of 51 patients with an ABLE score <4.5, no poor outcomes of death or lung transplantation were achieved.

At a two-year evaluation point, the CF-ABLE score proves to be a useful tool based on everyday clinical parameters, to concisely predict a patient's prognosis to an endpoint of death or transplant over a four year period.

1. McCarthy C, Dimitrov BD, Meurling IJ, Gunaratnam C, McElvaney NG; The CF-ABLE score: a novel clinical prediction rule for prognosis in patients with cystic fibrosis; Chest. 2013 May;143(5): 1358-64.
Abstract 3112: The Effect of Angiotensin-Converting Enzyme Inhibition on Progression of Aortic Sclerosis and Mortality
Authors: Reza Ardehali, Nicholas J Leeper, Paul A Heidenreich
Journal: Circulation (2006)

Introduction: Aortic sclerosis has many risk factors in common with atherosclerosis and is associated with an increased risk of cardiovascular death. We assessed the hypothesis that treatment with ...
Two‐dimensional speckle tracking echocardiography combined with high‐sensitive cardiac troponin <scp>T</scp> in early detection and prediction of cardiotoxicity during epirubicine‐based chemotherapy
Authors: Yu Kang, Xiaoping Xu, Leilei Cheng, Lin Li, Minmin Sun, Haiyan Chen, Cuizhen Pan, Xianhong Shu
Journal: European Journal of Heart Failure (2013)
Individualized treatment regimens with second line anti-TB drugs (SLD) compared to first line anti-TB drug (FLD) only in new pulmonary TB patients, culture confirmed with full sensibility at drug sensibility test (DST)
Authors: Domnica Chiotan, Cristian Didilescu, Niculae Galie, Radu Posea, Constantin Marica
Journal: European Respiratory Journal (2011)

Background: SLD are known as less efficient than FLD. However in clinical practice some of new pulmonary confirmed, fully sensible at DST TB cases are treated with individualized anti-TB regimens containing SLD.  Material and method: In Romania, 3845 new, pulmonary culture-confirmed TB cases, with full sensibility at DST registered between 01.01.2006-31.01.2007 were analyzed for anti-TB treatment regimen, treatment outcome, duration of treatment.  Results: Out of 3845 cases, 79 (2.1%) cases were treated with regimens containing at least one SLD for at least one month and 3766 (97,9%) were treated with FLD only.  Out of 79 cases treated with mixed FLD-SLD, 61 (77.1%) were successfully treated. Out of 3766 cases treated with FLD only, 3309 (87.7%) were successfully treated. The difference between the success rates was statistically significant (p  Conclusions: Individualized treatment regimens with SLD should be kept only for very few cases with severe adverse reaction against FLD.  NTP-s must assure uninterrupted supply with at least FLD
Use of an inactivated vaccine in mitigating pandemic influenza A(H1N1) spread: a modelling study to assess the impact of vaccination timing and prioritisation strategies
Authors: V Sypsa, I Pavlopoulou, A Hatzakis
Journal: Eurosurveillance (2009)

The impact of prioritization and of timing of vaccination strategies on reducing transmission of pandemic influenza A(H1N1) was evaluated in a community with the structure of the Greek population using a stochastic simulation model. Prioritization scenarios were based on the recommendations of the United States Centers for Disease Control and Prevention Advisory Committee on Immunization Practices and vaccination was assumed to initiate either before or during the ongoing epidemic. In the absence of intervention, an illness attack rate (AR) of 34.5% is anticipated. Vaccinating the priority groups before the epidemic (pregnant women, people who live with or care for children <6 months of age, healthcare/emergency services personnel, children 6 months-4 years old and high-risk children 5-18 years old) will have a negligible impact on the overall AR. Vaccinating the recommended groups before the epidemic (priority groups as well as all persons 6 months-24 years old and high-risk individuals 25-64 years old) is anticipated to result in overall and age-specific ARs within the range of seasonal influenza (5%-15%). Initiating vaccination early during the epidemic (AR<or=1% of the population) is predicted to result in overall ARs up to 15.2%-19.9% depending on daily vaccination coverage rates. When vaccination is initiated at a later stage (AR: 5%), only coverage of 80% of the whole population at intensive daily vaccination rates would be able to reduce ARs to approximately 15%.
A DSM-III family study of the nonschizophrenic psychotic disorders
Authors: K S Kendler, A M Gruenberg, M T Tsuang
Journal: American Journal of Psychiatry (1986)

The authors conducted a blind DSM-III family study based on probands diagnosed from long-term follow-up information as having schizophreniform disorder, schizoaffective disorder, or psychotic affective illness. The pattern of psychopathology in relatives of schizophreniform probands closely resembled that found previously in relatives of schizophrenic probands. Relatives of schizoaffective probands had an excess risk for schizophrenia, other psychoses, and bipolar illness. The pattern of illness found in relatives of the probands meeting Research Diagnostic Criteria for mainly schizophrenic schizoaffective disorder appeared indistinguishable from that of relatives of schizophrenic probands. Relatives of probands with psychotic affective disorder had an excess risk for schizophrenia and for unipolar and bipolar affective disorder.
The role of genetic polymorphism of NO-synthase in the implementation of the “atopic march”
Authors: Konstantin Rukin
Journal: European Respiratory Journal (2011)

NO-synthase genes are candidate for development bronchial asthma (BA) and atopic dermatitis (AD), because nitric oxide and its metabolites are involved in the formation of oxidative stress and nitrolizing. We planned and conducted study of the following polymorphisms: 276 C/T, -186 A/C gene nNOS; -954 G/C, (CCTTT) n, (TAAA) n gene iNOS; 894 C/G and VNTR gene eNOS.  The aim of the study. Set polymorphisms NO-synthase gene associated with clinical and functional manifestations of bronchial asthma and atopic dermatitis for the formation of molecular predictors of implementation of the “atopic march”.   Materials and methods:  Material study were DNA samples of patients with asthma (n = 929), BA (n = 847), AD + BA (n = 460). As a control, the DNA of healthy subjects (n = 720).   Results:  Established genotypes increase the risk of formation of “atopic march”: TT genotype polymorphism 276 C/T, AC polymorphism 186 A/C gene nNOS (RR = 4,56, p = 0,003); 220/220 polymorphism (TAAA) n, GC and CC polymorphism - 954G/C, x/x on the number of repeats (CCTTT) n gene iNOS (RR = 1,60, p = 0,002); aa polymorphism VNTR, CG polymorphism 894C/G gene of eNOS (RR = 3,75, p = 0,001).  Found haplotypes of genes involved in the implementation of the “atopic march”atopic march”: (nNOS, iNOS, eNOS): T276 (276C/T, nNOS) + C186 (-186A/C, nNOS) + X (CCTTT) n, NOS + G954 (- 954G/C, iNOS) +220 (TAAA) n, iNOS, + G894 (894C/G, eNOS) + a (VNTR), eNOs.
Regulation of Peroxisome Proliferator-activated Receptor γ Expression in Human Asthmatic Airways
Authors: LAURENT BENAYOUN, SÉVERINE LETUVE, ANNE DRUILHE, JORGE BOCZKOWSKI, MARIE-CHRISTINE DOMBRET, PATRICIA MECHIGHEL, JÉRÔME MEGRET, GUY LESECHE, MICHEL AUBIER, MARINA PRETOLANI
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Airway inflammation and alterations in cellular turnover are histopathologic features of asthma. We show that the expression of peroxisome proliferator-activated receptor γ (PPAR γ ), a nuclear hormone receptor involved in cell activation, differentiation, proliferation, and/or apoptosis, is augmented in the bronchial submucosa, the airway epithelium, and the smooth muscle of steroid-untreated asthmatics, as compared with control subjects. This is associated with enhanced proliferation and apoptosis of airway epithelial and submucosal cells, as assessed by the immunodetection of the nuclear antigen Ki67, and of the cleaved form of caspase-3, respectively, and with signs of airway remodeling, including thickness of the subepithelial membrane (SBM) and collagen deposition. PPAR γ expression in the epithelium correlates positively with SBM thickening and collagen deposition, whereas PPAR γ expressing cells in the submucosa relate both to SBM thickening and to the number of proliferating cells. The intensity of PPAR γ expression in the bronchial submucosa, the airway epithelium, and the smooth muscle is negatively related to FEV1 values. Inhaled steroids alone, or associated with oral steroids, downregulate PPAR γ expression in all the compartments, cell proliferation, SBM thickness, and collagen deposition, whereas they increase apoptotic cell numbers in the epithelium and the submucosa. Our findings have demonstrated that PPAR γ (1) is a new indicator of airway inflammation and remodeling in asthma; (2) may be involved in extracellular matrix remodeling and submucosal cell proliferation; (3) is a target for steroid therapy.
Zanamivir for influenza: a public health perspective
Authors: J. S Nguyen-Van-Tam
Journal: BMJ (1999)

Influenza epidemics cause much disruption, including time off school and work, and increased demands on health services. Though the incidence of infection is highest in children and young adults, serious complications, including death, are commonest in elderly people and those suffering from “high risk” chronic illnesses.1 In Britain annual influenza vaccination is therefore recommended for high risk patients and those aged 75 years and over. Despite offering worthwhile reductions in both mortality and hospital admissions, influenza vaccine is underused.2 3

Zanamivir has recently been licensed in Australia, Sweden, and the United Kingdom for treating influenza. Another similar compound, ostelamivir, is waiting in the wings. Created by computer assisted design, the drug works by inhibiting the neuraminidase activity of both influenza type A and B viruses.4 5 Although its bioavailability through oral administration is poor, zanamivir is successfully delivered as a nasal spray or dry powder inhalation.

Randomised, double blind, placebo controlled trials of zanamivir for preventing and treating experimental human influenza have established that the drug is safe, well tolerated, and reduces viral shedding by a median of three days.6 In a large randomised, double blind, placebo controlled trial among healthy adults, zanamivir …
Association Between Experimental Pain Biomarkers and Serologic Markers in Patients With Different Degrees of Painful Knee Osteoarthritis
Authors: Lars Arendt‐Nielsen, Thomas N. Eskehave, Line L. Egsgaard, Kristian K. Petersen, Thomas Graven‐Nielsen, Hans C. Hoeck, Ole Simonsen, Anne S. Siebuhr, Morten Karsdal, Anne C. Bay‐Jensen
Journal: Arthritis & Rheumatology (2014)

To assess the association between pain mechanisms (sensitization) and biochemical markers for cartilage, bone, and inflammation in patients with knee pain.The study group comprised 281 patients with different degrees of knee pain intensity and radiographic findings (using the Kellgren/Lawrence [K/L] scale). The following structurally related serologic biomarkers were measured in serum: high-sensitivity C-reactive protein (hsCRP), matrix metalloproteinase (MMP)-mediated breakdown of CRP (CRPM), MMP-mediated degradation of type I collagen (C1M), C2M, and C3M. Pressure-pain thresholds (PPT) (peripheral and spreading sensitization), temporal summation of pain, and conditioning pain modulation (CPM) (with the latter 2 biomarkers representing generalized sensitization) were assessed. For each pain parameter, the patients were categorized as most sensitized or least sensitized.Correlations were observed between the pain biomarkers PPT, temporal summation, and CPM and maximal pain intensity during the last 24 hours. Significant associations between most of the serologic biomarkers were observed. A high CRPM level was associated with centralized sensitization (temporal summation and CPM). None of the serologic markers correlated with the intensity or duration of knee pain, and only hsCRP correlated with the K/L grade. The most-sensitized group contained more women than men, and the least-sensitized group contained more men than women.A platform of mechanistic pain biomarkers in combination with structure-related serologic biomarkers provides new possibilities for understanding how osteoarthritis-related structural features may be associated with pain and pain sensitization. This study showed significant correlations between central pain sensitization and CRPM as a possible measure for chronic inflammation. Future pain association studies should include biomarkers representing the local joint environment more specifically.
The protective effect of rural living against atopy in Mongolia
Authors: A. Viinanen, S. Munhbayarlah, T. Zevgee, L. Narantsetseg, Ts. Naidansuren, M. Koskenvuo, H. Helenius, E. O. Terho
Journal: Allergy (2007)

Background: Farm environment in childhood protects against atopy. We investigated in a population‐based study in Mongolia the effects of rural living and migration from rural to urban areas on the risk of atopy. Methods: The screening study data of 9453 subjects, aged 10–60 years, were used for taking the sample for the clinical study in which 869 subjects were examined. Asthma, allergic rhinoconjunctivitis and sensitization were clinically defined and their risk factors analysed by logistic regression. Results: The risks of allergic rhinoconjunctivitis [adjusted odds ratio (OR) 0.43, 95% confidence interval (CI) 0.19–0.98] and allergic sensitization (OR 0.26, 95% CI 0.13–0.55) were the lowest in subjects living in a village from birth and intermediate in subjects who had relocated from a village to a town (OR for rhinoconjunctivitis 0.68, 95% CI 0.36–1.27, OR for sensitization 0.62, 95% CI 0.35–1.12) compared with subjects living in a town from birth. Simultaneous exposure to herd animals and dung heating decreased the risk of atopy. Keeping animals was a risk‐factor for asthma only in Ulaanbaatar city. Conclusions: Continuing farm exposure after childhood may be important in reducing the risk of atopy.
Application of evidence‐based dentistry: from research to clinical periodontal practice
Authors: Vivien Kwok, Jack G. Caton, Alan M. Polson, Paul G. Hunter
Journal: Periodontology 2000 (2012)

Abstract Dentists need to make daily decisions regarding patient care, and these decisions should essentially be scientifically sound. Evidence‐based dentistry is meant to empower clinicians to provide the most contemporary treatment. The benefits of applying the evidence‐based method in clinical practice include application of the most updated treatment and stronger reasoning to justify the treatment. A vast amount of information is readily accessible with today’s digital technology, and a standardized search protocol can be developed to ensure that a literature search is valid, specific and repeatable. It involves developing a preset question ( p opulation, i ntervention, c omparison and o utcome; PICO) and search protocol. It is usually used academically to perform commissioned reviews, but it can also be applied to answer simple clinical queries. The scientific evidence thus obtained can then be considered along with patient preferences and values, clinical patient circumstances and the practitioner’s experience and judgment in order to make the treatment decision. This paper describes how clinicians can incorporate evidence‐based methods into patient care and presents a clinical example to illustrate the process.
Quality of life and psychiatric morbidity in panic disorder and generalized anxiety disorder
Authors: A O Massion, M G Warshaw, M B Keller
Journal: American Journal of Psychiatry (1993)

This report examines the impact of panic disorder and/or generalized anxiety disorder on quality of life and the implications of these findings on nosological categories.A total of 357 subjects with a current episode of panic disorder and/or generalized anxiety disorder were diagnosed according to DSM-III-R criteria, using structured clinical interviews, as part of a prospective, naturalistic, longitudinal, multicenter study of a clinical population with anxiety disorders.There was a high degree of coexistence of anxiety disorders and major depressive disorder. Subjects with generalized anxiety disorder almost universally had other disorders, were the most likely to have at least one other anxiety disorder or major depressive disorder at intake, had the earliest age at onset, and had the worst emotional health rating. Subjects with panic disorder without agoraphobia had the most likelihood of a history of alcohol abuse. Nine percent of the subjects had a history of suicide attempts or gestures.The subjects showed significant impairment in quality of life. The highly frequent coexistence of other anxiety disorders with generalized anxiety disorder and the overall lack of differences on many quality of life measures raise questions of nosology, particularly for generalized anxiety disorder.
Comparison of signal transduction drug response markers in immortalized cell lines and primary patient specimens
Authors: Kyra D. Ceceris, Paul R. Ervin, Theresa R. Cassino
Journal: Clinical Cancer Research (2010)

Abstract Background: The epidermal growth factor pathway is an important driver of cancer growth. Erlotinib is a small molecule protein-kinase inhibitor targeting the epidermal growth factor receptor (EGFR) that may benefit a select subtype of cancer patients. However, identification of the characteristics of patients who may benefit from the use of erlotinib is not easy. Previous publication explored the activation of signal transduction proteins in the EGFR pathway as a method of determining erlotinib response and demonstrated that lung cancer cell lines characterized by increased pEGFR/pAKT ratios are more resistant to erlotinib. The aim of this study was to compare the activation of signal transduction markers in the EGFR pathway between immortalized cell lines and primary cultures of patient-derived tumor cells. Predictive potential of pEGFR/pAKT ratios in both immortalized cell lines and primary cultures of lung cancer cells was also compared. Methods: Western blotting and In-Cell western analysis were used to determine the activation state of the EGFR signaling pathway. Signaling pathway components were compared in the presence and absence of erlotinib treatment in immortalized lung cancer cell lines and primary cultures of lung cancer specimens. Chemosensitivity of cell lines and specimens to erlotinib was determined using an in vitro drug response marker. Cells were treated with a 10 dose concentration range of erlotinib for 72 hours and the remaining post-treatment live cells were enumerated by nuclear staining. Results: The pEGFR/pAKT ratio was increased in erlotinib-responsive immortalized cell lines when compared to non-responsive cell lines (p&amp;lt;0.05). This difference in pEGFR/pAKT ratio was significant after treatment with erlotinib as well. The difference in pEGFR/pAKT ratios in response to erlotinib treatment between erlotinib-responsive and non-responsive primary cultures of lung cancer cells was not, however, statistically significant. Conclusion: These studies confirmed that pEGFR/pAKT ratios may be indicative of erlotinib response in immortalized lung cancer cell lines. However, when evaluating the signal transduction markers in patient-derived primary cultures, no correlation with in vitro erlotinib response was found. These results highlight the value of using in vitro drug response markers, which utilize primary patient tissue, in the development of predictive biomarkers.
Deletion of the Dystrophin Muscle-Promoter Region Associated with X-Linked Dilated Cardiomyopathy
Authors: Francesco Muntoni, Milena Cau, Antonello Ganau, Rita Congiu, Giuseppina Arvedi, Anna Mateddu, Maria Giovanna Marrosu, Carlo Cianchetti, Giuseppe Realdi, Antonio Cao, Maria Antonietta Melis
Journal: New England Journal of Medicine (1993)

Several forms of hereditary dilated cardiomyopathy have been identified; with the exception of those resulting from mutations of mitochondrial DNA,1,2 no pathological finding can be used to differentiate the conditions, so their distinction depends on the pattern of transmission. Autosomal recessive, autosomal dominant, and matrilinear forms have been reported; several families with X-linked dilated cardiomyopathy have also been described3–5. X-linked dilated cardiomyopathy is a progressive myocardial disease presenting as congestive heart failure in teenage boys without clinical signs of skeletal myopathy5. No information is available on the pathogenetic defect involved in this disorder, although cardiomyopathy is . . .