tbuckley/cabot-search huggingface dataset:
Photochemical Targeting of Epidermal Growth Factor Receptor: A Mechanistic Study
Authors: Mark D. Savellano, Tayyaba Hasan
Journal: Clinical Cancer Research (2005)

Photoimmunotherapy may allow target-specific photodynamic destruction of malignancies and may also potentiate anticancer antibody therapies. However, clinical use of either of the two modalities is limited for different reasons. Antibody therapies suffer from being primarily cytostatic and the need for prolonged administration with consequent side effects. In the case of photoimmunotherapy, a major impediment has been the absence of well-characterized photosensitizer immunoconjugates (PIC). In this investigation, we suggest a strategy to overcome these limitations and present the successful targeting of epidermal growth factor receptor (EGFR) using a well-characterized PIC.The PIC consisted of the EGFR-recognizing chimeric monoclonal antibody, C225, conjugated with a two-branched polyethylene glycol and benzoporphyrin derivative (BPD, Verteporfin). Mechanistic studies included photophysics, phototoxicity, cellular uptake, and catabolism experiments to yield dosimetric parameters. Target cells included two EGFR-overexpressing human cancer cell lines, OVCAR-5 and A-431. Nontarget cells included an EGFR-negative fibroblast cell line, 3T3-NR6, and a monocyte-macrophage cell line, J774.BPD-C225 PICs targeted and photodynamically killed EGFR-overexpressing cells, whereas free BPD exhibited no specificity. On a per mole basis, PICs were less phototoxic than free BPD, but PICs were very selective for target cells, whereas free BPD was not. Phototoxicity of the PICs increased at prolonged incubations. Photodynamic dose calculations indicated that PIC photophysics, photochemistry, catabolism, and subcellular localization were important determinants of PIC phototoxic potency.This study shows the efficacy of EGFR targeting with PIC constructs and suggests approaches to improve PIC designs and targeting strategies for in vivo photoimmunotherapy. The approach offers the possibility of dual effects via antibody-mediated cytostasis and photoimmunotherapy-based cytotoxicity.
Ankle taping and bracing for proprioception
Authors: Kasper W Janssen, Steven J Kamper
Journal: British Journal of Sports Medicine (2012)

▸  Raymond J, Nicholson LL, Hiller CE, et al . The effect of ankle taping or bracing on proprioception in functional ankle instability: a systematic review and meta-analysis. J Sci Med Sport 2012 online doi.org/10.1016/j.jsams.2012.03.008.

Ankle injuries account for up to 20% of sports-related injuries,1 of these 33–73% are sprains, most commonly of the lateral ligament complex. This high incidence and the functional consequences ensure that patients with ankle sprains present frequently to sports medical practises. The serious consequences of a sprain include ongoing instability and recurrence,2 although it is unclear as to what physiological changes following the original injury predispose an individual to these consequences. One hypothesis is that proprioception, which refers to a group of sensations, including sense of movement, sense of joint position and sensations related to muscle force,3 is impaired following the first ankle sprain. Taping or a brace placed in direct contact with the skin is thought to improve proprioceptive acuity by stimulating cutaneous mechanoreceptors. Ankle taping or bracing is commonly used by those who have experienced an ankle sprain as a means of preventing further injury. Generally, tape and braces are hypothesised to reduce ankle sprain risk by providing mechanical support to the joint and also by improving proprioception.4 ,5

To determine whether ankle taping or bracing compared to no taping or bracing improves proprioception in people with a history of ankle sprain or functional ankle instability.

Eight biomedical databases including …
Anti-cyclic citrullinated peptide revised criteria for the classification of rheumatoid arthritis
Authors: K P Liao, K L Batra, L Chibnik, P H Schur, K H Costenbader
Journal: Annals of the Rheumatic Diseases (2008)

The classification of rheumatoid arthritis (RA) is increasingly important as new therapies can halt the disease in its early stages. Antibodies to cyclic citrullinated peptides (anti-CCP) are widely used for RA diagnosis, but are not in the 1987 American College of Rheumatology (ACR) Criteria for RA Classification. We developed and tested the performance characteristics of new criteria for RA classification, incorporating anti-CCP.We identified all subjects seen in our arthritis centre with rheumatoid factor (RF) and anti-CCP tested simultaneously between 1 January and 30 June 2004 and reviewed their medical records for the ACR criteria, rheumatologists' diagnoses, RF and anti-CCP. We revised the ACR criteria in two ways: (a) adding anti-CCP, and (b) replacing rheumatoid nodules and erosions with anti-CCP (CCP 6 criteria). We compared sensitivity and specificity of all criteria, in all subjects and in subjects with arthritis symptoms </=6 months.Medical records of 292 subjects were analysed: mean age was 54 years, 82% were women, and mean symptom duration was 4.1 years. 17% were RF positive and 14% were anti-CCP positive at initial testing. 78 (27%) had definite RA per treating rheumatologist at latest follow-up. The CCP 6 criteria increased sensitivity for RA classification for all subjects regardless of symptom duration: 74% vs 51% for ACR criteria with a loss in specificity (81% vs 91%). Sensitivity was greatly improved in subjects with symptoms < or =6 months: 25% vs 63% for ACR criteria with a decrease in specificity.The CCP 6 criteria improved upon the sensitivity of the ACR criteria, most remarkably for subjects with symptoms < or =6 months and could be used for the classification of subjects for RA in clinical studies.
Changes in the Health Education Authority
Authors: B. Haward
Journal: BMJ (1995)

EDITOR,—Jack Warden chronicles the government's relation to the Health Education Authority and refers to the report produced under the chairmanship of John Lee, which was submitted to the government in November 1993.1 He states that this report is thought to have advised drastic reform of the authority, if not abolition.

I was a member of the committee that produced the report; I have experience in health promotion as I was a director of public health at the time. …
Associations between arterial calcification and stiffness, bone density, emphysema and all-cause mortality in COPD patients
Authors: Elisabeth Romme, David McAllister, John Murchison, Edwin Van Beek, George Petrides, Erica Rutten, Frank Smeenk, Emiel Wouters, William MacNee
Journal: European Respiratory Journal (2013)

Background: Cardiovascular disease, osteoporosis and emphysema are associated with COPD. However, associations between these factors in COPD patients are not well understood.  Objective: To examine associations between markers of cardiovascular disease (coronary artery calcification [CAC], thoracic aortic calcification [TAC] and arterial stiffness), bone density (bone attenuation of the thoracic vertebrae [BATV]), emphysema (PI-950 and 15th percentile) and all-cause mortality in a COPD cohort.  Methods: We measured arterial stiffness as carotid-radial pulse wave velocity (PWV) in a COPD cohort. We assessed CAC, TAC, BATV, PI-950 and 15th percentile on chest CT and identified deaths from a national register.  Results: We studied 119 COPD subjects; aged 67.8 ±7.3, 66% were males and mean FEV1 % predicted was 46.0 ±17.5. Subjects were classified into three pre-specified groups: CAC=0 (n=14), 0 400 (n=64). Subjects with higher CAC were more likely to be older (p  Conclusion: Increased CAC was associated with increased arterial stiffness and lower bone density, and CAC, TAC and extent of emphysema predicted all-cause mortality in a COPD cohort.
Microaneurysm Turnover at the Macula Predicts Risk of Development of Clinically Significant Macular Edema in Persons With Mild Nonproliferative Diabetic Retinopathy
Authors: Maria Luisa Ribeiro, Sandrina G. Nunes, José G. Cunha-Vaz
Journal: Diabetes Care (2012)

To examine the relationship between microaneurysm (MA) turnover using automated analysis of fundus photographs (RetmarkerDR; Critical Health SA) and development of clinically significant macular edema (CSME) in nonproliferative diabetic retinopathy (NPDR).A prospective, monocenter, observational study was designed to follow eyes/patients with type 2 diabetes and NPDR (Early Treatment Diabetic Retinopathy Study levels 20 and 35) with no prior laser treatment for 2 years or until development of CSME. A total of 410 patients, one eye per patient, fulfilled the inclusion/exclusion criteria and were included in the study. Ophthalmologic examinations including best corrected visual acuity, fundus photography, and optical coherence tomography were performed at baseline, 6 months, and at the last study visit (24 months or before laser treatment).A total of 348 eyes/patients performed the 24-month visit or developed CSME. Of these 348 eyes/patients, 26 developed CSME. HbA1c levels at baseline and MA turnover (i.e., the sum of the MA formation and disappearance rates) computed during the first 6 months of follow-up were found to be independently predictive factors for development of CSME. MA turnover was 11.2 ± 11.2 in the 26 eyes/patients that developed CSME and 5.0 ± 5.2 in the remaining 322 (P < 0.001). Higher MA turnover values correlated with earlier development of CSME. MA turnover predictive values for CSME development were, for the positive predictive value, 20% and for the negative predictive value, 96%.MA turnover calculated with the RetmarkerDR predicts development of CSME in eyes with NPDR. Low MA turnover values identify well the eyes that are less likely to develop CSME in a 2-year period.
Adhesion-Independent α6β4 Integrin Clustering Is Mediated by Phosphatidylinositol 3-Kinase
Authors: Michael Z. Gilcrease, Xiao Zhou, Kristin Welch
Journal: Cancer Research (2004)

Abstract Clustering of cell-surface integrins is known to augment integrin-mediated signal transduction, but mechanisms of integrin clustering are poorly understood. Here we report that adhesion-independent clustering of α6β4 integrin, known to be important in mediating tumor cell motility, is driven by phosphatidylinositol 3-kinase (PI3K) but does not require activation of the PI3K-Akt pathway. We observed clustering of α6β4 in breast carcinoma cells after adhesion-independent cross-linking of the β4 integrin subunit. Clustering was significantly blocked when cross-linking was performed in the presence of PI3K inhibitors LY294002 and wortmannin. In contrast, no significant inhibition of clustering was observed with protein kinase C inhibitor GF109203X, rapamycin, or heparin. Although α6β4 clustering was blocked by PI3K inhibitors, clustering was not associated with increased PI3K lipid kinase activity or increased phosphorylation of Akt. A novel role for PI3K in α6β4 integrin clustering is proposed.
Postoperative outcome of Crohn’s disease in 30 children
Authors: M Besnard, O Jaby, J F Mougenot, L Ferkdadji, A Debrun, C Faure, P Delagausie, M Peuchmaur, Y Aigrain, J Navarro, J P Cézard
Journal: Gut (1998)

Background —Thirty children operated on for Crohn’s disease (CD) were reviewed (1975–1994). The aim of the study was to assess their postoperative outcome. Patients —19 boys and 11 girls, aged 15.3 (2) years (range 11.3–20) at surgery were studied. Results —Surgical indications were acute complications of CD and chronic intestinal illness. Six months after surgery, 11 of 12 patients had been weaned off steroids, and 22 of 23 patients were weaned off nutritional support; 17 patients without recurrrence had a mean (SD) weight gain of 2.1 (8) kg and a height gain of 3.36 (3) cm. During 3.1 (2.7) years follow up, 12 patients (40%) had a recurrence of the disease after 19.4 (14) months (means (SD)): supra-anastomotic recurrence (six), severe perianal disease (two), and chronic illness (four). Six of 14 patients who were treated with mesalazine (13) or azathioprine (one) had recurrences. The postoperative recurrence rate was 50% at two years. Conclusion —Surgical treatment modifies the immediate outcome of severe or complicated CD, but does not prevent recurrence, despite localised resection or prophylactic postoperative treatment. Extension of the disease before surgery seems to be a major risk factor for postoperative recurrence in children.
Effects of an atrial natriuretic peptide receptor antagonist on glomerular hyperfiltration in diabetic rats.
Authors: P L Zhang, H S Mackenzie, J L Troy, B M Brenner
Journal: Journal of the American Society of Nephrology (1994)

Previous studies from this laboratory implicated atrial natriuretic peptide (ANP) as a possible mediator of glomerular hyperfiltration in diabetic rats. In this study, the potential of HS-142-1 (HS), a novel polysaccharide compound with ANP receptor antagonist properties, to ameliorate glomerular hyperfiltration in diabetic rats was assessed. Initially, it was confirmed that a bolus iv injection of HS blocked both diuretic and natriuretic responses to exogenous ANP in normal Munich-Wistar rats. The acute effects of HS in moderately hyperglycemic diabetic rats with glomerular hyperfiltration and hyperperfusion were then determined. In diabetic rats, HS (20 mg/kg bolus iv) lowered GFR by approximately 46% from hyperfiltering (1.86 +/- 0.06 mL/min) to normal (1.13 +/- 0.13 mL/min) levels, whereas GFR in vehicle-treated diabetic rats remained unchanged (1.92 +/- 0.08 mL/min to 1.77 +/- 0.09 mL/min). In nondiabetic euvolemic rats, GFR was reduced by 20% after HS, whereas GFR in vehicle-treated controls was unchanged. In contrast, HS had no effect on GFR in hydropenic rats. Effective RPF was not significantly reduced in either diabetic or normal euvolemic rats in response to HS; consequently, significant reductions in filtration fraction were observed in both groups. Urine flow and sodium excretion rates were significantly reduced after HS in both diabetic and nondiabetic groups but not in hydropenic or vehicle-treated groups. These data show that HS ameliorates glomerular hyperfiltration in diabetic rats, further supporting the hypothesis that intrarenal actions of natriuretic peptides contribute significantly to glomerular hyperfiltration in experimental diabetes mellitus.
The Assessment of SpondyloArthritis international Society (ASAS) handbook: a guide to assess spondyloarthritis
Authors: J Sieper, M Rudwaleit, X Baraliakos, J Brandt, J Braun, R Burgos-Vargas, M Dougados, K-G Hermann, R Landewe, W Maksymowych, D van der Heijde
Journal: Annals of the Rheumatic Diseases (2009)

The field of spondyloarthritis (SpA) has experienced major progress in the last decade, especially with regard to new treatments, earlier diagnosis, imaging technology and a better definition of outcome parameters for clinical trials. In the present work, the Assessment in SpondyloArthritis international Society (ASAS) provides a comprehensive handbook on the most relevant aspects for the assessments of spondyloarthritis, covering classification criteria, MRI and <i>x</i> rays for sacroiliac joints and the spine, a complete set of all measurements relevant for clinical trials and international recommendations for the management of SpA. The handbook focuses at this time on axial SpA, with ankylosing spondylitis (AS) being the prototype disease, for which recent progress has been faster than in peripheral SpA. The target audience includes rheumatologists, trial methodologists and any doctor and/or medical student interested in SpA. The focus of this handbook is on practicality, with many examples of MRI and <i>x</i> ray images, which will help to standardise not only patient care but also the design of clinical studies.
Differences in responsiveness to hyperventilation and methacholine in asthma and chronic bronchitis.
Authors: E H Ramsdale, R S Roberts, M M Morris, F E Hargreave
Journal: Thorax (1985)

In a previous study on 27 patients with chronic bronchitis we found that only three developed bronchoconstriction in response to hyperventilation of cold, dry air despite an increased responsiveness to methacholine inhalation. We therefore investigated bronchial responsiveness to hyperventilation with cold, dry air and methacholine in 27 patients with stable asthma who had a similar range of baseline FEV1 values but who developed bronchoconstriction that could be reversed to give an FEV1 more than 70% of the predicted value. Baseline FEV1 was 0.88-3.98 l (37-114% predicted). All but one subject developed bronchoconstriction in response to hyperventilation. There was a linear relationship between baseline FEV1 and response to methacholine (r2 = 0.37, p less than 0.001) and the relationship was significantly different from that found in the bronchitic subjects (F2.50 = 24.94, p less than 0.001). In general, the response to methacholine was greater in the asthmatic than in the bronchitic subjects for any baseline FEV1. The results suggest that there are different mechanisms underlying the increased responsiveness to methacholine in asthma and chronic bronchitis.
Mice with a severe deficiency in protein C display prothrombotic and proinflammatory phenotypes and compromised maternal reproductive capabilities
Authors: Angelina J. Lay, Zhong Liang, Elliot D. Rosen, Francis J. Castellino
Journal: Journal of Clinical Investigation (2005)

Anticoagulant protein C (PC) is important not only for maintenance of normal hemostasis, but also for regulating the host immune response during inflammation. Because mice with a designed total genetic deficiency in PC (PC–/– mice) die soon after birth, attempts to dissect PC function in various coagulation/inflammation-based pathologies through use of mice with less than 50% of normal PC levels have not been successful to date. In the current investigation, we have used a novel transgenic strategy to generate different mouse models expressing 1–18% of normal PC levels. In contrast to PC–/– mice, mice with only partial PC deficiency survived beyond birth and also developed thrombosis and inflammation. The onset and severity of these phenotypes vary significantly and are strongly dependent on plasma PC levels. Our findings additionally provide the first evidence that maternal PC is vital for sustaining pregnancy beyond 7.5 days postcoitum, likely by regulating the balance of coagulation and inflammation during trophoblast invasion. These low PC–expressing transgenic mouse lines provide novel animal models that can be used to elucidate the importance of PC in maintenance of the organism and in disease.
Antibiotic Treatment of Children With Sore Throat
Authors: Jeffrey A. Linder
Journal: JAMA (2005)

ContextOf children with sore throat, 15% to 36% have pharyngitis caused by group A β-hemolytic streptococci (GABHS). Performance of a GABHS test prior to antibiotic prescribing is recommended for children with sore throat. Penicillin, amoxicillin, erythromycin, and first-generation cephalosporins are the recommended antibiotics for treatment of sore throat due to GABHS.ObjectivesTo measure rates of antibiotic prescribing and GABHS testing and to evaluate the association between testing and antibiotic treatment for children with sore throat.Design, Setting, and ParticipantsAnalysis of visits by children aged 3 to 17 years with sore throat to office-based physicians, hospital outpatient departments, and emergency departments in the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, 1995 to 2003 (N = 4158) and of a subset of visits with GABHS testing data (n = 2797).Main Outcome MeasuresNational rates of antibiotic prescribing, prescribing of antibiotics recommended and not recommended for GABHS, and GABHS testing.ResultsPhysicians prescribed antibiotics in 53% (95% confidence interval [CI], 49%-56%) of an estimated 7.3 million annual visits for sore throat and nonrecommended antibiotics to 27% (95% CI, 24%-31%) of children who received an antibiotic. Antibiotic prescribing decreased from 66% of visits in 1995 to 54% of visits in 2003 (P = .01 for trend). This decrease was attributable to a decrease in the prescribing of recommended antibiotics (49% to 38%; P = .002). Physicians performed a GABHS test in 53% (95% CI, 48%-57%) of visits and in 51% (95% CI, 45%-57%) of visits at which an antibiotic was prescribed. GABHS testing was not associated with a lower antibiotic prescribing rate overall (48% tested vs 51% not tested; P = .40), but testing was associated with a lower antibiotic prescribing rate for children with diagnosis codes for pharyngitis, tonsillitis, and streptococcal sore throat (57% tested vs 73% not tested; P&lt;.001).ConclusionsPhysicians prescribed antibiotics to 53% of children with sore throat, in excess of the maximum expected prevalence of GABHS. Although there was a decrease in the proportion of children receiving antibiotics between 1995 and 2003, this was due to decreased prescribing of agents recommended for GABHS. Although GABHS testing was associated with a lower rate of antibiotic prescribing for children with diagnosis codes of pharyngitis, tonsillitis, and streptococcal sore throat, GABHS testing was underused.
Epidemiological modelling of routine use of low dose aspirin for the primary prevention of coronary heart disease and stroke in those aged ≥70
Authors: Mark R Nelson, Danny Liew, Melanie Bertram, Theo Vos
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To investigate the routine use of low dose aspirin in people aged ≥ 70 without overt cardiovascular disease. <b>Design</b> Epidemiological modelling in a hypothetical population. <b>Setting</b> Reference populations of men and women in the year 2000 from the state of Victoria, Australia. <b>Subjects</b> 10 000 men and 10 000 women aged 70-74 with no cardiovascular disease. <b>Main outcome measures</b> First ever myocardial infarction or unstable angina, ischaemic or haemorrhagic stroke, and major gastrointestinal haemorrhage. Health adjusted years of life lived. <b>Results</b> The proportional benefit gained from the use of low dose aspirin by the prevention of myocardial infarctions (−389 in men, −321 in women) and ischaemic stroke (−19 in men and −35 in women) is offset by excess gastrointestinal (499 in men, 572 in women) and intracranial (76 in men, 54 in women) bleeding. The results in health adjusted years of life lived (which take into account length and quality of life) are equivocal for aspirin causing net harm or net benefit. <b>Conclusion</b> Epidemiological modelling suggests that any benefits of low dose aspirin on risk of cardiovascular disease in people aged ≥ 70 are offset by adverse events. These findings are tempered by wide confidence intervals, indicating that the overall outcome could be beneficial or adverse.