tbuckley/cabot-search huggingface dataset:
Airway basement membrane thickness in children with asthma
Authors: Maria Lykogeorgou, Polytimi Panaghiotopoulou Gartagani, Michael Choulakis, Athanasios Kaditis, Anastasia Georgountzou, Kalliopi Stefanaki, George Chrousos, Vasiliki Gemou Engesaeth
Journal: European Respiratory Journal (2013)

Background:Asthma is characterized by chronic airway inflammation involving mainly increased numbers of eosinophils, mast cells and T-lymphocytes. “Airway remodeling” refers to structural changes, one of which is thickening of reticular basement membrane (RBM).  Aim: To assess whether RBM thickness is associated with age, atopic status, lung function and other parameters in asthmatic children.  Methods:Fifteen children with asthma underwent bronchoscopy and bronchial mucosa biopsy. Formalin fixed, paraffin-embedded tissues of the bronchial biopsies were used for the measurement of RBM thickness with the micrometric lens adjusted on photomicroscope. Immunohistochemistry was performed on paraffin section for the detection of B- cell [CD20/L-26] and T-cell [CD3/PS-1] markers. Atopic status was assessed by measuring total IgE and specific IgE antibodies to common allergens.  Results:Fifteen children (7 atopic, 8 non- atopic) with asthma were studied, aged 5-11 years. RBM thickness ranged from 2 to 5μ and was >3μ in 9/15 subjects. There was no difference in RBM thickness between atopic and non-atopic children (p=0.217). Moreover, there was no association of RBM thickness with age (p=0.819), FEV1 (p=0.906), eosinophilia vs no eosinophilia in bronchial mucosa (p=0.402), eosinophilia vs no eosinophilia in blood (p=0.415) and the use of inhaled corticosteroids (median dose 250-500 mcg fluticazone /24h) (p=0.143). Biopsies of asthmatic children with atopy showed a trend for an increased number of CD3+ T lymphocytes in lamina propria of the bronchial mucosa.  Conclusions:In our series, there was no significant correlation of RBM thickness with the severity of asthma, possibly because the most participants had mild to moderate disease.
Docetaxel Alone or in Combination With a Therapeutic Cancer Vaccine (PANVAC) in Patients With Metastatic Breast Cancer
Authors: Christopher R. Heery, Nuhad K. Ibrahim, Philip M. Arlen, Mahsa Mohebtash, James L. Murray, Kimberly Koenig, Ravi A. Madan, Sheri McMahon, Jennifer L. Marté, Seth M. Steinberg, Renee N. Donahue, Italia Grenga, Caroline Jochems, Benedetto Farsaci, Les R. Folio, Jeffrey Schlom, James L. Gulley
Journal: JAMA Oncology (2015)

Previous phase 1 and 2 trials of PANVAC, a poxviral-based cancer vaccine, have suggested clinical efficacy in some patients with breast, ovarian, and colorectal cancer and have shown evidence of immunologic activity. Preclinical data have shown that docetaxel can modify tumor phenotype, making tumor cells more amenable to T cell-mediated killing.The goal of this study was to determine if the treatment combination of docetaxel and PANVAC improves clinical outcomes in patients with metastatic breast cancer compared with docetaxel treatment alone.Between May 2006 and February 2012, this open-label, phase 2 randomized clinical trial enrolled 48 patients with metastatic breast cancer of all subtypes, without limitation on other lines of previous therapy, to receive treatment with either docetaxel with PANVAC (arm A) or docetaxel alone (arm B). Final clinical data were collected on September 16, 2013. All patients were treated at either the National Cancer Institute or the Department of Breast Medical Oncology, MD Anderson Cancer Center.The primary end point was progression-free survival (PFS), using a phase 2.5 statistical design, with the intent of identifying a trend toward benefit (defined as 1-sided P≤.10) to guide a larger trial design. Secondary end points included safety and immunologic correlative studies.Forty-eight participants were enrolled: 25 were randomized to the combination treatment arm A, and 23 to arm B. No patient remained in the study at the time of the final analysis. Patient and tumor characteristics were well matched. Analysis of adverse events in both treatment arms demonstrated very little difference between the 2 groups. In the combination treatment arm (arm A), statistically significant increases were noted in the frequency of grades 1 and 2 edema (P=.02, likely related to greater median number of docetaxel cycles) and injection-site reactions (P<.001). In the final data analysis, median PFS was 7.9 months in arm A vs 3.9 months in arm B (hazard ratio, 0.65 [95% CI, 0.34-1.14]; P=.09).The results suggest that the combination of PANVAC with docetaxel in metastatic breast cancer may provide a clinical benefit. This study was hypothesis generating and provides both rationale and statistical assumptions for a larger definitive randomized study.clinicaltrials.gov Identifier: NCT00179309.
Increased isoprostane and prostaglandin are prominent in neurons in Alzheimer disease
Authors: Gemma Casadesus, Mark A Smith, Samar Basu, Jing Hua, Dae E Capobianco, Sandra L Siedlak, Xiongwei Zhu, George Perry
Journal: Molecular Neurodegeneration (2007)

Abstract Background Inflammation and oxidative stress are both involved in the pathogenesis of Alzheimer disease and have been shown to be reciprocally linked. One group of molecules that have been directly associated with inflammation and the production of free radicals are the prostaglandin 13,14-dihydro 15-keto PGF 2α and the isoprostane 8-iso-PGF 2α . Results To further delineate the role of inflammatory and oxidative parameters in Alzheimer disease, in this study we evaluated the amount and localization of 13,14-dihydro 15-keto PGF 2α and 8-iso-PGF 2α in hippocampal post mortem tissue samples from age-matched Alzheimer disease and control patients. Our results demonstrate increased levels of 13,14-dihydro 15-keto PGF 2α and 8-iso-PGF 2α in the hippocampal pyramidal neurons of Alzheimer disease patients when compared to control patients. Conclusion These data not only support the shared mechanistic involvement of free radical damage and inflammation in Alzheimer disease, but also indicate that multiple pathogenic "hits" are likely necessary for both the development and propagation of Alzheimer disease.
Measuring visual acuity in general practice
Authors: R. D Neal, T. James
Journal: BMJ (1995)

excision or mastectomy for breast cancer is prob- ably at least 20%,2 and mild discomfort may be experienced even more commonly.The pain is usually a late onset phenomenon, developing any- thing from a few months to several years after treatment.This problem is frequently encountered in both hospital and general practice, and failure to recog- nise the syndrome can lead to much anxiety for the patient and often fruitless and unnecessary investigations.
Abstract 13900: Hyperamylinemia Exacerbates Sarcolemmal Lipid Peroxidation in Diabetic Hearts
Authors: Miao Liu, Xiao Li Peng, Sanda Despa, Kenneth Margulies, Florin Despa
Journal: Circulation (2014)

Background:  Chronic hypersecretion of the pancreatic hormone amylin leads to infiltration of oligomeric amylin in cellular membranes, which contributes to β-cell dysfunction and type-2 diabetes (T2D). We recently showed that oligomeric amylin also accumulates in myocardium of patients with obesity or T2D.   Hypothesis:  Oligomeric amylin may infiltrate the sarcolemma exposing membrane lipids to peroxidation by ROS, thus exacerbating myocardial oxidative stress.   Methods:  We investigated the relationship between incorporated amylin and lipid peroxidation in ventricular myocytes from obese patients (BMI≥30) with heart failure (HF) (O-HF group; N=6), obese humans without HF (O-NF group; N=6) and healthy people with BMI   Results:  Compared to L-NF controls, the myocyte level of amylin is increased in both O-HF group (10-fold; P 11 -BODIPY and Liperfluo indicates increased lipid peroxidation in HIP rat myocytes (2-fold; P   Conclusions:  Together, these findings support the hypothesis that circulating oligomeric amylin infiltrates cardiac myocytes in humans and exacerbates lipid peroxidation. Strategies to mitigate myocardial deposition of amylin should be pursued.
Close observation in intensive care unit is required when naloxone infusion ends
Authors: S. Finfer
Journal: BMJ (1996)

infusion ended, an event better supervised during the normal working day.We do not agree that all patients with methadone overdose should be admitted empirically for 72 hours or that pulse oximetry should be performed continuously for this time.This would result in unnecessarily protracted admissions and inappropriate use of monitoring equipment.Pulse oximetry will not detect hypoventilation in a patient being given supplemental oxygen.'After an initial bolus, the early introduction of a naloxone infusion titrated to the clinical response is appropriate management; this can be stopped after 12-24 hours with the patient kept under close clinical scrutiny for sev- eral hours thereafter, particular attention being paid to the conscious level and respiratory rate and depth.Any deterioration in these variables necessitates resumption of the naloxone infusion with an initial bolus as required.In summary, in this case flumazenil was inappropriately given and the use of naloxone can best be described as too little, with the infusion being given too late and stopped too soon, apparently without adequate clinical supervision.The clinical toxicology results are interesting, but only in relation to the postmortem discussion.The lessons in this case are not those advanced by the authors.
The clinical utility of basophil activation testing in diagnosis and monitoring of allergic disease
Authors: H. J. Hoffmann, A. F. Santos, C. Mayorga, A. Nopp, B. Eberlein, M. Ferrer, P. Rouzaire, D. G. Ebo, V. Sabato, M. L. Sanz, T. Pecaric-Petkovic, S. U. Patil, O. V. Hausmann, W. G. Shreffler, P. Korosec, E. F. Knol
Journal: Allergy (2015)

The basophil activation test (BAT) has become a pervasive test for allergic response through the development of flow cytometry, discovery of activation markers such as CD63 and unique markers identifying basophil granulocytes. Basophil activation test measures basophil response to allergen cross-linking IgE on between 150 and 2000 basophil granulocytes in <0.1 ml fresh blood. Dichotomous activation is assessed as the fraction of reacting basophils. In addition to clinical history, skin prick test, and specific IgE determination, BAT can be a part of the diagnostic evaluation of patients with food-, insect venom-, and drug allergy and chronic urticaria. It may be helpful in determining the clinically relevant allergen. Basophil sensitivity may be used to monitor patients on allergen immunotherapy, anti-IgE treatment or in the natural resolution of allergy. Basophil activation test may use fewer resources and be more reproducible than challenge testing. As it is less stressful for the patient and avoids severe allergic reactions, BAT ought to precede challenge testing. An important next step is to standardize BAT and make it available in diagnostic laboratories. The nature of basophil activation as an ex vivo challenge makes it a multifaceted and promising tool for the allergist. In this EAACI task force position paper, we provide an overview of the practical and technical details as well as the clinical utility of BAT in diagnosis and management of allergic diseases.
Abstract 1295: The Vasomotor Effects of Apelin in vivo in Man
Authors: Alan G Japp, Nicholas L Cruden, David A Amer, Ewan B Goudie, Neil R Johnston, David J Webb, Ian L Megson, Andrew D Flapan, David E Newby
Journal: Circulation (2007)

BACKGROUND In preclinical models, apelin, the endogenous ligand for the G protein-coupled APJ receptor, lowers systemic venous tone, causes nitric oxide (NO)-mediated arterial vasodilatation and is the most potent inotrope yet studied. We aimed to establish the in vivo vasomotor effects of apelin in man. METHODS Dorsal hand vein diameter was measured by the Aellig technique in 6 subjects during local intravenous infusions (0.1–3 nmol/min) of two apelin agonists, apelin-36 and (Pyr1)apelin-13, and sodium nitroprusside (SNP; 0.6 nmol/min) in the presence and absence of norepinephrine preconstriction. Forearm blood flow (FBF) responses to intrabrachial infusions of apelin-36 and (Pyr1)apelin-13 (0.1–30 nmol/min) were measured by venous occlusion plethysmography in 8 subjects on 4 occasions. In a 2×2 factorial design, a further 8 subjects received an intrabrachial infusion of (Pyr1)apelin-13 (0.3–3 nmol/min) in the presence or absence of the NO clamp (NO synthase inhibitor, L-N-monomethylarginine (8 micromol/min), co-infused with SNP (1–128 ng/min) to maintain basal flow and clamp endogenous NO production), and following a single oral dose of aspirin (600 mg) or matched placebo. RESULTS Although SNP caused venodilatation (P&lt;0.0001), apelin-36 and (Pyr1)apelin-13 had no effect on dorsal hand vein diameter in the presence or absence of norepinephrine (P=0.2). Both apelin-36 and (Pyr1)apelin-13 caused reproducible dose-dependent vasodilatation in forearm resistance vessels (P&lt;0.0001): maximal increase of 198+/−27% and 90+/−7% respectively. Vasodilatation had a rapid onset (within 6 min) and slow offset that remained 36 min post-infusion (P&lt;0.01). Plasma apelin concentrations and non-infused FBF (P&lt;0.05) were increased at doses &gt;3 nmol/min, consistent with systemic spillover. (Pyr1)apelin-13-mediated vasodilatation was attenuated by the NO clamp (AUC reduced by 64%; P=0.004) but was unaffected by aspirin (P=0.7). CONCLUSION Although having no apparent effect on venous tone, apelin causes a rapid onset and sustained NO-dependent arterial vasodilatation in vivo in man. The apelin-APJ system merits further clinical investigation to determine its role in cardiovascular homeostasis and its therapeutic potential in heart failure.
Abstract 15233: Presence of Endothelial Colony-Forming Cells is Associated With Reduction of Microvascular Obstruction Limiting Infarct Size and Left Ventricular Remodelling: A Magnetic Resonance Imaging Study in Patients With Acute Myocardial Infarction
Authors: Nicolas Meneveau, Frederic Deschaseaux, Marie-France Seronde, Vincent Descotes-Genon, Francois Schiele, David Chalmers, Pierre Tiberghien, Jean-Pierre Bassand, Jean-Pierre Kantelip, Siamak Davani
Journal: Circulation (2010)

Background: Endothelial colony-forming cells (ECFCs) have proliferative and vasculogenic capacities and can be detected in patients with myocardial infarction (MI). Although high levels of ECFCs ha...
Abstract 17712: Comparison of Three-Dimensional and Two-Dimensional Quantitative Coronary Angiography and Intravascular Ultrasound for the Functional Assessment of Coronary Lesions
Authors: Takeshi Nishi, Takashi Nakayama, Yoshihide Fujimoto, Yoshio Kobayashi
Journal: Circulation (2014)

Introduction: Three-dimensional (3-D) quantitative coronary angiography (QCA) reportedly allows a more accurate depiction of true vessel geometry when compared with standard two-dimensional (2-D) QCA and has been validated by intravascular ultrasound (IVUS). Although IVUS is currently thought to provide the most accurate measurements of vessel geometry and lesion severity, 3-D QCA measurements can be performed on existing standard coronary angiography images without the need for additional time or equipment during the procedure. Hypothesis: We assessed the hypothesis that 3-D QCA measurements and IVUS are comparable in accuracy in predicting physiologically significant stenosis assessed by fractional flow reserve (FFR). Methods: Forty lesions in 38 patients were assessed by FFR, IVUS, and 2-D and 3-D QCA. Correlations between anatomical data and FFR were analyzed. The area under the receiver-operating characteristic (ROC) curve (AUC) was calculated to identify the accuracy of predicting FFR ≤0.80. Results: Mean FFR value was 0.75 ± 0.13. FFR ≤0.80 was observed in 26 lesions (65%). Of all measurements of lesion severity obtained by IVUS, minimum lumen diameter (MLD) (r = 0.80, p &lt;0.001) and minimum lumen area (MLA) (r = 0.72, p &lt;0.001) were well correlated with FFR values. Of all 3-D QCA measurements, MLA correlated best with FFR values (r = 0.75, p &lt;0.001). Of all 2-D QCA measurements, MLD correlated best with FFR values (r = 0.58, p &lt;0.001). The AUC were 0.95 for MLA by IVUS, 0.93 for MLD by IVUS, 0.93 for MLA by 3-D QCA, and 0.78 for MLD by 2-D QCA (Figure). Conclusions: Anatomical parameters obtained by 3-D QCA and IVUS correlate better with FFR values than those obtained by 2-D QCA. The predictive value of 3-D QCA for reduced FFR is comparable to IVUS measurements.
What happens when the private sector plans hospital services for the NHS: three case studies under the private finance initiative
Authors: A. M Pollock, M. Dunnigan, D. Gaffney, A. Macfarlane, F A. Majeed
Journal: BMJ (1997)

We aim to promote efficiency, to improve services and to stimulate fresh flows of investment. We want to harness the private sector's management expertise and resources, bringing a new approach to investment in a whole range of activities and services traditionally regarded as the exclusive domain of the public sector. Kenneth Clarke, chancellor of the exchequer , November 1993

The private finance initiative (PFI) for public sector projects was launched by the government in 1992 to transform “public sector organisations from being owners of assets and direct providers of services into purchasers of services from the private sector.”1 The types of projects funded under the scheme range from the building and operation of trunk roads, computer systems, and vehicle fleets to the construction of hospitals and delivery of NHS support systems.2 New hospitals are leased back to the NHS at market rates for 20-60 years. NHS land and buildings are often sold to the private companies as part of the deal.

We consider here some of the implications of the use of private capital to fund NHS hospital developments, based on the plans produced for those schemes that have reached an advanced stage (table 1). We look at three of these in detail. A second wave of trusts already negotiating contracts include trusts in Glasgow, Newcastle, and the Midlands. Given the speed with which trusts have taken up the private finance initiative, it is important to examine the assumptions underlying the projects and the impact these projects will have on health services in their localities. First wave schemes will affect around 5% of acute NHS beds in England and almost a quarter in Scotland. Hence these projects are not just a local issue. They indicate the likely configuration of hospital services in England and Scotland if current policies …
Abstract 419: Cytokine-Mediated Release of Vascular Endothelial Growth Factor and Stromal-Derived Factor 1 Induces Neovascularization and Prevents Left Ventricular Remodeling in a Porcine Model of Ischemia Reperfusion.
Authors: Franca S Angeli, Sarah Jahn, Nicolas Amabile, Gina Orcino, Mia Shapiro, Sukesh Burjonroppa, Petros Minasi, Kanu Chatterjee, William Grossman, Yerem Yeghiazarians
Journal: Circulation (2007)

Cytokine therapy has been suggested to improve left ventricle (LV) function after myocardial infarction (MI). The mechanisms for this benefit remain debatable. We investigated the impact of a prolonged combined therapy with Darbepoetin alfa (DARB) and Granulocyte Colony-Stimulating Factor (G-CSF) on LV function and vascular density after MI, correlating it with circulating progenitor cells (CPC), Vascular Endothelial Growth Factor (VEGF) and Stromal-Derived Factor 1 (SDF-1) release. Methods and Results : MI was induced in swine by a 90 minutes balloon occlusion of the left anterior descending artery. Animals were divided between treatment group with DARB-GCSF combination therapy (bolus of DARB 0.9 and GCSF 10ug/kg IV at time of reperfusion, followed by 5 doses of GCSF 5ug/kg SC from day 5 to 9, and four doses of 0.45ug/kg DARB SC once per week starting at day 1, n = 8) or control group (saline injections, n = 8). White blood cells (WBC), CPC, defined by CD45, CD31, CD90 and SLA-1 expression, and circulating levels of VEGF and SDF-1 were assessed at baseline (T0), 1 (T1), 2 (T2), and 3 (T3) weeks post-MI. LV function was assessed by echocardiography at T0, T1 and T6 (6 weeks post-MI), and vascular density by histology at T6. MI size was the same in both groups by post-MI CPK peak and LV ejection fraction (EF) at T1 (41+/−1 vs. 40+/−2%). In the treatment group only, from T0 to T1, there was an increase in WBC (16 ± 2 to 42 ± 2 x 10 6 /ml, p &lt;0.01) and CPC (5 ± 1 to 9 ± 1 x 10 5 /ml, p = 0.01) and SDF-1 levels peaked from T0 to T2 (1345+/−60 to 1554 +/− 60 pg/ml; p&lt;0.01) and stabilized at T3. All these values remained unchanged in the control group. VEGF levels (pg/ml) peaked at T2 in both groups (14+/−1 vs. 12+/−1), but remained increased at T3 in DARB-GCSF group only (13+/−1 vs. 9+/−1; p&lt;0.01). LVEF (41+/−1 vs. 33+/−1, p&lt;0.01) and arteriole density at the infarct zone (44+/−14 vs. 27+/−12/mm 2 , p = 0.02) and remote zone (18 +/−8 vs.11+/−5, p = 0.055) were higher compared to the control at T6. Conclusion : Our data suggest that prolonged therapy with DARB-GCSF combination after MI modulates angiogenesis and promotes stabilization of LV function by increasing CPC, and releasing SDF-1 and VEGF. This therapy provides a novel strategy to prevent post-MI LV remodeling and potentially improve outcome.
Prognostic value and clinical significance of halo naevi regarding vitiligo
Authors: N. van Geel, S. Vandenhaute, R. Speeckaert, L. Brochez, I. Mollet, L. De Cooman, J. Lambert
Journal: British Journal of Dermatology (2010)

Vitiligo and halo naevi can present together or separately. Whether they are different entities remains unclear.To assess the clinical significance of halo naevi, both with respect to the future development of vitiligo, and to the clinical profile and course of vitiligo.In total, 291 patients were included in this study: patients with only halo naevi (group 1; n=40), patients with generalized vitiligo without halo naevi (group 2; n=173) and patients with generalized vitiligo with halo naevi (group 3; n=78).Patients with only halo naevi (group 1) reported significantly less associated autoimmune disease (P=0·001), were less likely to have a family history of vitiligo (P=0·013) and were less likely to have presence of Koebner phenomenon (P<0·001) compared with patients with generalized vitiligo (groups 2+3). Multiple halo naevi (≥3) were significantly more frequently observed (P=0·002) in patients from group 1 compared with patients from group 3. In group 3, halo naevi were reported prior to the development of vitiligo in 61% (mean±SD time interval of 33·7±5·17months). No significant correlation was observed between the presence of halo naevi and the extent, activity or subtype of vitiligo. However, halo naevi in patients with vitiligo significantly reduced the risk for associated autoimmune diseases, and age at onset of vitiligo was significantly lower compared with patients with vitiligo without halo naevi (P<0·001).Our results support the hypothesis that halo naevi can represent a distinct condition. In a subset of patients, the occurrence of halo naevi may be an initiating factor in the pathogenesis of vitiligo.