tbuckley/cabot-search huggingface dataset:
S10 Is a high FeNO a marker of non-adherence in difficult asthma?
Authors: D. M. McNicholl, L. P. McGarvey, L. G. Heaney
Journal: Thorax (2011)

<h3>Background</h3> Non-adherence to inhaled combination therapy (ICT) is a major contributor to poor control in difficult asthma1; however identifying non-adherence in this population is challenging. We have shown that suppression of fractional exhaled nitric oxide (FeNO), following directly observed inhaled corticosteroid can identify non-adherence2; it has previously been suggested that a single high FeNO measurement can identify non-adherence in difficult asthma. <h3>Methods</h3> We performed a retrospective analysis of patients attending a difficult asthma clinic between January 2007 and December 2010. Prescription refill data, patient demographics, FeNO and lung function were collated. ICT prescription refill ratio % was calculated as the number of doses refilled/number of doses prescribed over 6 months × 100.1 Non-parametric correlation analysis was performed. Tests for non-adherence defined as ICT prescription refill cut-offs of &lt;80% and &lt;50% were assessed. <h3>Results</h3> One hundred and forty-six patients underwent systematic evaluation during the time period. Patient characteristics are displayed in Abstract S10 table 1. FeNO level and ICT prescription refill ratio did not correlate significantly (r=−0.11, p=0.2). For FeNO &gt;45 ppb, there was a trend with ICT prescription refill ratio of &lt;80% (p=0.06); significant in patients not prescribed oral steroids (n=99, p=0.016). No relationship existed between FeNO &gt;100 ppb at both prescription refill ratio cut-offs. Using FeNO &gt;45 ppb to define non-adherence, negative (NPV) and positive predictive values (PPV) were: 66% and 61% for &lt;80% ICT prescription refill ratio; 71% and 33% for &lt;50% prescription refill ratio. Using FeNO &gt;100 ppb, NPV and PPV were: 55% and 52% for &lt;80%; 69% and 32% for &lt;50% prescription refill ratio. <h3>Conclusion</h3> While there is a weak relationship between a single point-in-time FeNO measurement and non-adherence to ICT in difficult asthma, this cannot be used as an alternative to our previously described FeNO suppression test.
Changing Ethnic Disparity in Ischemic Stroke Mortality in US Children After the STOP Trial
Authors: Laura L. Lehman, Heather J. Fullerton
Journal: JAMA Pediatrics (2013)

A prior report showed higher stroke mortality in US black children compared with white children (1979-1998), a disparity likely due in part to sickle cell disease, which leads to a high risk of childhood ischemic stroke. We hypothesized that this disparity has diminished since the publication of the Stroke Prevention Trial in Sickle Cell Anemia (STOP trial) in 1998 demonstrating the efficacy of long-term blood transfusions for primary stroke prevention.To evaluate the demographics and secular trends in mortality from ischemic and hemorrhagic stroke (as a primary cause of death) in US children (<20 years) and determine if there has been a decrease in the disparity between white and black children since the publication of the STOP trial in 1998.We used death certificate data from the National Center for Health Statistics, 1988 through 2007.United States.Children who died in 1988 through 2007 in the United States.Publication of the STOP trial.Incidence rate ratios were calculated as the measure of relative risk.Among 1.6 billion person-years of US children (1988-2007), there were 4425 deaths attributed to stroke, yielding an average of 221 deaths per year; 20% were ischemic; 67%, hemorrhagic; and 12%, unspecified. The relative risk of ischemic stroke mortality for black vs white children dropped from 1.74 from 1988 through 1997 to 1.27 from 1998 through 2007. The ethnic disparity in hemorrhagic stroke mortality, however, remained relatively stable between these 2 periods: black vs white relative risk, 1.90 (1988-1997) and 1.97 (1998-2007).The excess risk of death from ischemic, but not hemorrhagic, stroke in US black children has decreased over the past decade. This may be related to the implementation of an effective ischemic stroke prevention strategy for children with sickle cell disease.
Giant left atrium
Authors: B. T. Le Roux, M. S. Gotsman
Journal: Thorax (1970)

Radiographic evidence of asymmetrical enlargement of the left atrium without atrial infarction is presented. Giant atrial enlargement is rarely symmetrical, the atrial appendage can contribute to the enlargement, and the giant atrium can be effectively trimmed. This will reduce its size and, therefore, the space which it occupies, and will restore the anatomical relations of neighbouring structures such as the main bronchi.
Deficit of Somatostatin in the Vitreous Fluid of Patients With Diabetic Macular Edema
Authors: Rafael Simó, Esther Carrasco, Alex Fonollosa, Josep García-Arumí, Roser Casamitjana, Cristina Hernández
Journal: Diabetes Care (2007)

Although diabetic macular edema (DME) is the main cause of visual loss in type 2 diabetic patients (1), its pathogenic mechanisms have been much less studied than proliferative diabetic retinopathy (PDR). The production of both somatostatin (SST) and its receptors by the retina suggests an autocrine action. However, the functional roles of this peptidergic system in retinal physiology are far from being fully elucidated. In recent years we have demonstrated that SST is decreased in the vitreous fluid from patients with PDR, SST-28 being the main molecular variant accounting for this deficit (2,3). Apart from angiostatic properties, SST has anti-inflammatory and anti-edema effects (4–9). Therefore, it is possible that its deficit can be involved not only in PDR but also in DME development.

The aim of the present study was to determine whether, as occurs in PDR, a deficit of intravitreous SST also exists in DME, thus allowing us to identify a new potential pathogenic contributor to this devastating complication of diabetes. Since SST-28 is the main molecular variant in the vitreous fluid, it has been selected as the ideal candidate to be explored.

The study included 35 type 2 diabetic patients (15 with DME and 20 with PDR), in whom a classic three port pars plana vitrectomy was performed. Vitreous from 30 age-matched nondiabetic patients (18 with macular hole and 12 with idiopathic epiretinal membrane) served as the control group. The exclusion criteria were as follows: 1 ) previous vitreoretinal surgery, 2 ) recent vitreous hemorrhage or intravitreous hemoglobin >5 mg/ml, or 3 ) photocoagulation in the preceding 3 months. Fluorescein angiography was performed in all patients with DME in order to assess …
Five-Year Clinical Follow-Up After Intracoronary Radiation
Authors: Mark A. Grise, Vincent Massullo, Shirish Jani, Jeffrey J. Popma, Robert J. Russo, Richard A. Schatz, Erminia M. Guarneri, Stephen Steuterman, David A. Cloutier, Martin B. Leon, Prabhakar Tripuraneni, Paul S. Teirstein
Journal: Circulation (2002)

Background — Several clinical trials indicate that intracoronary radiation is safe and effective for treatment of restenotic coronary arteries. We previously reported 6-month and 3-year clinical and angiographic follow-up demonstrating significant decreases in target lesion revascularization (TLR) and angiographic restenosis after γ radiation of restenotic lesions. The objective of this study was to document the clinical outcome 5 years after treatment of restenotic coronary arteries with catheter-based iridium-192 ( 192 Ir). Methods and Results — A double-blind, randomized trail compared 192 Ir to placebo sources in patients with restenosis after coronary angioplasty. Over a 9-month period, 55 patients were enrolled; 26 were randomized to 192 Ir and 29 to placebo. At 5-year follow-up, TLR was significantly lower in the 192 Ir group (23.1% versus 48.3%; P =0.05). There were 2 TLRs between years 3 and 5 in patients in the 192 Ir group and none in patients in the placebo group. The 5-year event-free survival rate (freedom from death, myocardial infarction, or TLR) was greater in 192 Ir-treated patients (61.5% versus 34.5%; P =0.02). Conclusions — Despite apparent mitigation of efficacy over time, there remains a significant reduction in TLR at 5 years and an improvement in event-free survival in patients treated with intracoronary 192 Ir. The early clinical benefits after intracoronary γ radiation with 192 Ir seem durable at 5-year clinical follow-up.
Special Aspects of Neuropsychiatric Illness in Women: With a Focus on Depression
Authors: Jean A. Hamilton, Uriel Halbreich
Journal: Annual Review of Medicine (1993)

Many depressive disorders predominate in women. Other psychiatric disorders more prevalent in women than men often occur concomitantly with depression. A variety of these disorders show a premenstrual patterning of symptoms and are responsive to antidepressants. Migraine headaches are also more common in women, show a premenstrual patterning, and are responsive to antidepressants. Other neuropsychiatric and endocrine-related disorders predominating in women are discussed in this review. Greater attention to the special aspects of neuropsychiatric disorders in women may improve diagnosis and treatment.
Overuse injuries of the musculoskeletal system, 2nd edn
Authors: J Saunders
Journal: British Journal of Sports Medicine (2006)

Edited by Marco M Pecina, Ivan Bojanic. Published by CRC Press, 2004, pp 421, £79.00, hardcover. ISBN 0849314283

This book generally gives a very good outline of overuse injuries of the musculoskeletal system. I was a little intrigued by the order of the chapters, with magnetic resonance imaging being the second chapter straight after the introduction. This was offset by discussion of ultrasound use in the …
Autosomal Dominant Polycystic Kidney Disease
Authors: Arlene B. Chapman
Journal: Journal of the American Society of Nephrology (2007)

Diagnosis and treatment of autosomal dominant polycystic kidney disease (ADPKD) is rapidly changing. Cellular pathways that involve the polycystins are being mapped and involve the primary cilium, intracellular calcium and cAMP regulation, and the mammalian target of rapamycin (mTOR) pathway. With the use of new imaging approaches, earlier diagnosis of hepatic cystic disease is possible, and measurement of kidney and cystic growth as well as kidney blood flow is possible over relatively short periods. PKD gene type, gender, proteinuria, and the presence of hypertension relate to the rate of kidney growth in ADPKD. On the basis of risk factors for progression to ESRD and the pathogenic roles that intracellular cAMP and mTOR play in cystogenesis, novel therapies are now being tested, including maximal inhibition of the renin-angiotensin system, inhibition of renal intracellular cAMP using vasopressin V2 receptor antagonists, and somatostatin analogues, as well as inhibitors of mTOR. This review addresses the current understanding of the pathogenesis and the natural history of ADPKD; accuracy and reliability of diagnostic approaches in utero, childhood, and adulthood; the value of reliable magnetic resonance imaging to measure disease progression early in the course of ADPKD; and novel therapeutic approaches that are being evaluated in ADPKD.
Non-volitional assessment of skeletal muscle strength in patients with chronic obstructive pulmonary disease
Authors: W D-C Man, M G G Soliman, D Nikoletou, M L Harris, G F Rafferty, N Mustfa, M I Polkey, J Moxham
Journal: Thorax (2003)

Although quadriceps weakness is well recognised in chronic obstructive pulmonary disease (COPD), the aetiology remains unknown. In disabled patients the quadriceps is a particularly underused muscle and may not reflect skeletal muscle function as a whole. Loss of muscle function is likely to be equally distributed if the underlying pathology is a systemic abnormality. Conversely, if deconditioning and disuse are the principal aetiological factors, weakness would be most marked in the lower limb muscles.The non-volitional technique of supramaximal magnetic stimulation was used to assess twitch tensions of the adductor pollicis, quadriceps, and diaphragm muscles (TwAP, TwQ, and TwPdi) in 22 stable non-weight losing COPD patients and 18 elderly controls.Mean (SD) TwQ tension was reduced in the COPD patients (7.1 (2.2) kg v 10.0 (2.7) kg; 95% confidence intervals (CI) -4.4 to -1.4; p<0.001). Neither TwAP nor TwPdi (when corrected for lung volume) differed significantly between patients and controls (mean (SD) TwAP 6.52 (1.90) N for COPD patients and 6.80 (1.99) N for controls (95% CI -1.5 to 0.97, p=0.65; TwPdi 23.0 (5.6) cm H(2)O for COPD patients and 23.5 (5.2) cm H(2)O for controls (95% CI -4.5 to 3.5, p=0.81).The strength of the adductor pollicis muscle (and the diaphragm) is normal in patients with stable COPD whereas quadriceps strength is substantially reduced. Disuse may be the principal factor in the development of skeletal muscle weakness in COPD, but a systemic process preferentially affecting the proximal muscles cannot be excluded.
Remarks ON RADIUM THERAPY IN UTERINE CANCER
Authors: A. E. H. Pinch
Journal: BMJ (1921)

OF all diseases to which the femlMe sex is subject car- cinoma of the uterus is probably that most productive of constant discomfort, incessant p:ain, and evet'-present .mentalanguish.To a woman the dreaded diagnosis "cancer of the womb " often appears as the equivalent of '4death sentence.The expectation of life of untreated cases rarely exceeds two years, and in the majority of instances fifteen or -eiglhteen months sees a fatal termination.Until the introduction of Wertlheim's abdpminal hyster- .ectomy,surgical measures, if adopted, consisted eithier of local excision of the diseased cervix, or tlle performance of .v,aginalhysterectomy, operations #liich, in the majority of instances, were followed by speedy recurrence.Wertheim's l.ysterectomy in skilfulhands offers, however, a much better prospect of complete recovery from tlhe disease, but tle mortality attendant thereon cannot be liglltlv regarded, ?4J#d in many cases when the preliminary laparotomy has been performed an inspection of the pelvic cavity slhows th?at the disease is already too widely disseminited to permit of complete eradication.Other metllhoi triedl frbm 'time to time, consisting clliefly of the locfal application of, caustic pastes of one kind or another, have little' mioe than a transient palliative effect, the disease returning with renewed vigour so soon as the local reaction lhas subsided.Radium has been widely used for the treatment of carci- noma of tlle uterus, but thle results obtained by different vorkers have varied very greatly.Some claim that radium treatment should be used in all cases in preference -to operative measures, whilst others content themselves witlh saying that wlhilst it produces very great and definite symptomatic improvement, it never effects a cure of the disease.Tlle truth probably lies somewhere between these 'two views.CARCINOMA OF THE CERVIX.Classification of Cases. it would servo no useful purpose in a paper of tllis ehlaracter to discuss tlle vexed question as to the micro- scopical patlhology of carcinoma of the cervix uteri, and from tlle point of view of radium treatment it appears to mnatter little whether the growth originates in the columnnar cells of tlle mucous membrane of tlle upper two-thirds of tlhe cervical canal or from the squamous epithelium of the mucosa covering the cervix and the lower third of the cervical canal.In many instances microscopical sections 94how so much metaplasia of the .malignantcells that it ;i.impossible to say from which class of epithelium the growth originated.From the macroscopical appearances, however, it is justifiable to divide these growths clinically into three classes: 1 T'he Endocervical or Medullary Type.
The Iroquois Homeobox Gene 5 Is Regulated by 1,25-Dihydroxyvitamin D3 in Human Prostate Cancer and Regulates Apoptosis and the Cell Cycle in LNCaP Prostate Cancer Cells
Authors: Anne Myrthue, Brooks L.S. Rademacher, Janet Pittsenbarger, Bozena Kutyba-Brooks, Marin Gantner, David Z. Qian, Tomasz M. Beer
Journal: Clinical Cancer Research (2008)

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3], the most active metabolite of vitamin D3, has significant antitumor activity in a broad range of preclinical models of cancer. In this study, we show that the Iroquois homeobox gene 5 (Irx5) is down-regulated by 1,25(OH)2D3 in human prostate cancer samples from patients randomly assigned to receive weekly high-dose 1,25(OH)2D3 or placebo before radical prostatectomy. Down-regulation of Irx5 by 1,25(OH)2D3 was also shown in the human androgen-sensitive prostate cancer cell line LNCaP and in estrogen-sensitive MCF-7 breast cancer cells. Knockdown of Irx5 by RNA interference showed a significant reduction in LNCaP cell viability, which was accompanied by an increase in p21 protein expression, G2-M arrest, and an increase in apoptosis. The induced apoptosis was partially mediated by p53, and p53 protein expression was increased as a result of Irx5 knockdown. Cell survival was similarly reduced by Irx5 knockdown in the colon cancer cell line HCT 116 and in MCF-7 breast cancer cells, each being derived from clinical tumor types that seem to be inhibited by 1,25(OH)2D3. Overexpression of Irx5 led to a reduction of p21 and p53 expression. This is the first report that Irx5 is regulated by 1,25(OH)2D3 in humans and the first report to show that Irx5 is involved in the regulation of both the cell cycle and apoptosis in human prostate cancer cells. Irx5 may be a promising new therapeutic target in cancer treatment.
Incidence of rectosigmoid adenomatous polyps in subjects without prior colorectal adenoma or cancer: a prospective cohort study
Authors: B Paillot, P Czernichow, P Michel, V Merle, A-M Queuniet, C Duval, H Daubert
Journal: Gut (1999)

BACKGROUND Subjects without known colorectal adenomas or cancer constitute a large majority of the population where 85% of all cases of colorectal cancer are thought to occur. Consequently these people should be considered for screening to decrease mortality from colorectal cancer in the general population. AIMS To estimate the incidence rate of rectosigmoid adenomas in these subjects. METHODS Subjects without adenomas or cancer at a previous examination which had visualised the rectosigmoid underwent a fibre endoscopy every three years. Endoscopic data and population characteristics were collected prospectively. RESULTS A total of 450 subjects fulfilled the selection criteria; 287 (64%) underwent at least two examinations, and 163 had three or more. At the second examination, with a mean delay of 39 months, the incidence rate of rectosigmoïd adenomas was 1.50% per patient year. The rate was 1.75% per patient year (95% CI 0.80–3.33) at the third endoscopy with an additional mean delay of 38 months. The cumulative incidence rate at six years was 7.3% (95% CI 4.3–10.3), representing a mean of 1.2% per patient year. This rate increased with age and was higher for men than for women after age adjustment (p&lt; 0.03). CONCLUSIONS The incidence rates are very low compared with those of patients with prior adenomas. These results should be considered in establishing rectosigmoid adenoma screening strategies .
PET/CT Improves the Definition of Complete Response and Allows to Detect Otherwise Unidentifiable Skeletal Progression in Multiple Myeloma
Authors: Elena Zamagni, Cristina Nanni, Katia Mancuso, Paola Tacchetti, Annalisa Pezzi, Lucia Pantani, Beatrice Zannetti, Ilaria Rambaldi, Annamaria Brioli, Serena Rocchi, Carolina Terragna, Marina Martello, Giulia Marzocchi, Enrica Borsi, Ilaria Rizzello, Stefano Fanti, Michele Cavo
Journal: Clinical Cancer Research (2015)

To evaluate the role of 18F-FDG PET/CT in 282 symptomatic multiple myeloma patients treated up-front between 2002 and 2012.All patients were studied by PET/CT at baseline, during posttreatment follow-up, and at the time of relapse. Their median duration of follow-up was 67 months.Forty-two percent of the patients at diagnosis had >3 focal lesions, and in 50% SUVmax was >4.2; extramedullary disease was present in 5%. On multivariate analysis, ISS stage 3, SUVmax >4.2, and failure to achieve best complete response (CR) were the leading factors independently associated with shorter progression-free survival (PFS) and overall survival (OS). These 3 variables were used to construct a prognostic scoring system based on the number of risk factors. After treatment, PET/CT negativity (PET-neg) was observed in 70% of patients, whereas conventionally defined CR was achieved in 53%. Attainment of PET-neg favorably influenced PFS and OS. PET-neg was an independent predictor of prolonged PFS and OS for patients with conventionally defined CR. Sixty-three percent of patients experienced relapse or progression; in 12%, skeletal progression was exclusively detected by systematic PET/CT performed during follow-up. A multivariate analysis revealed that persistence of SUVmax >4.2 following first-line treatment was independently associated with exclusive PET/CT progression.PET/CT combined with ISS stage and achievement or not of CR on first-line therapy sorted patients into different prognostic groups. PET/CT led to a more careful evaluation of CR. Finally, in patients with persistent high glucose metabolism after first-line treatment, PET/CT can be recommended during follow-up, to screen for otherwise unidentifiable progression.
Non-invasive measurement of gastric accommodation in humans
Authors: W Schwizer, A Steingotter, M Fox, T Zur, M Thumshirn, P Bosiger, M Fried
Journal: Gut (2002)

Gastric accommodation describes the reduction in gastric tone and increase in compliance that follows ingestion of a meal and involves at least two responses: "receptive relaxation" which allows the stomach to accept a volume load without a significant rise in gastric pressure and "adaptive relaxation" which modulates gastric tone in response to the specific properties of the meal ingested. However, there are considerable technical difficulties in measuring the accommodation process. The current standard barostat studies, and other methods such as conventional and three dimensional ultrasound, or single photon emission computed tomography have significant disadvantages. Preliminary findings from the development and validation of a new magnetic resonance imaging technique that addresses many of the deficiencies of previous methods are presented.
Approaches for establishing the function of regulatory genetic variants involved in disease
Authors: Julian Charles Knight
Journal: Genome Medicine (2014)

The diversity of regulatory genetic variants and their mechanisms of action reflect the complexity and context-specificity of gene regulation. Regulatory variants are important in human disease and defining such variants and establishing mechanism is crucial to the interpretation of disease-association studies. This review describes approaches for identifying and functionally characterizing regulatory variants, illustrated using examples from common diseases. Insights from recent advances in resolving the functional epigenomic regulatory landscape in which variants act are highlighted, showing how this has enabled functional annotation of variants and the generation of hypotheses about mechanism of action. The utility of quantitative trait mapping at the transcript, protein and metabolite level to define association of specific genes with particular variants and further inform disease associations are reviewed. Establishing mechanism of action is an essential step in resolving functional regulatory variants, and this review describes how this is being facilitated by new methods for analyzing allele-specific expression, mapping chromatin interactions and advances in genome editing. Finally, integrative approaches are discussed together with examples highlighting how defining the mechanism of action of regulatory variants and identifying specific modulated genes can maximize the translational utility of genome-wide association studies to understand the pathogenesis of diseases and discover new drug targets or opportunities to repurpose existing drugs to treat them.