tbuckley/cabot-search huggingface dataset:
Abstract ED4-3: PET tracer for therapy monitoring
Authors: Hans-Jürgen Wester, Andreas Buck
Journal: Clinical Cancer Research (2010)

Abstract Molecular or metabolic imaging with PET plays a crucial role not only for the individual patient management but also for further validation of new therapies. The concept of using PET and [18F]fluorodeoxyglucose (FDG) for assessment of response is based on early changes in tumor glucose use which correlate to the effectiveness of a specific treatment. However, FDG-PET is a suitable surrogate marker for response prediction only in intensely FDG-avid tumors. For imaging in the context of planning of a chemotherapeutic intervention and for therapy monitoring, tracers with higher specificity are required. With the advent of molecular imaging, tumor tissue can be non-invasively characterized by imaging probes targeting biological processes such as metabolism, cell growth and migration as well as vascularization and oxygen tension. Based on such measurements signals can be defined which detect and quantitatively describe pharmacologic effects in tumor tissues within a few days after initiation of therapy. Initial results suggest that therapeutic strategies can be successfully adapted based on molecular imaging results, which are able to identify responders with improved clinical outcome. These specific and sensitive imaging signals are needed to match therapeutic targets with imaging agents addressing the same or corresponding biologic processes. Inhibiting neoangiogenesis, for example, represents an attractive therapeutic option, which benefits from imaging probes addressing molecular targets such as integrins and VEGF receptors as well as measuring perfusion and blood volume. Prior to treatment, these tracers enable to define the expression of a specific target. Alternative probes for molecular cancer imaging address metabolic key processes, such as cell proliferation ([18F]FLT), protein biosynthesis ([18F]FET, [11C]MET), neoangiogenesis ([18F]Galacto-RGD), hypoxia ([18F]FAZA), somatostatin receptor expression ([68Ga]DOTATOC), estrogen receptor expression ([18F]FES) or new concepts, such as cytokine / chemokine receptor expression ([68Ga]CPCR4). For response evalu ation, the tracer uptake has to correlate with the therapeutic effect at all imaging time points. Here, tracers with high sensitivity are required, allowing for the early assessment of therapeutic effects and response evaluation. Citation Information: Clin Cancer Res 2010;16(7 Suppl):ED4-3
Wheezing on Maximal Forced Exhalation in the Diagnosis of Atypical Asthma
Authors: Dennis K. King
Journal: Annals of Internal Medicine (1989)

Study Objective: To determine whether wheezing on maximal forced exhalation is a predictor of asthma in persons with normal or nearly normal baseline spirometry. Design: Prospective study of patients referred for methacholine challenge testing. Setting: Pulmonary function laboratory at a hospital. Patients: Forty-four patients referred for methacholine challenge testing because of the clinical suspicion of cough variant or otherwise difficult to diagnose asthma, with normal or nearly normal baseline spirometry and without wheezing on routine lung auscultation during quiet breathing. Interventions: We listened for wheezing on maximal forced exhalation. Wheezing was defined as a continuous sound with a musical quality. Methacholine challenge testing was done. The concentration of methacholine required to produce a 20% fall in baseline FEV1 (PC20) of less than 8 mg/mL was considered a positive test for asthma. Measurements and Main Results: Wheezing was present on maximal forced exhalation in 8 of 14 patients with a positive methacholine challenge test (sensitivity = 57%) and absent in 11 of 30 patients with a negative test (specificity = 37%). Furthermore, wheezing on maximal forced exhalation was present in 13 of 27 patients with a PC20 greater than 16 mg/mL and absent in 2 of 7 with a PC20 less than 4 mg/mL. Conclusions: Wheezing on maximal forced exhalation is neither sensitive nor specific for airway hyperreactivity.
Newer Methods for Evaluating Thyroid Nodules
Authors: Isadore N. Rosenberg
Journal: New England Journal of Medicine (1972)

The usefulness of classifying thyroid nodules according to their capacity for accumulating radioiodine as revealed by scintiscans is well established; thyroid cancer occurs much more frequently in nonfunctioning or "cold" nodules than in "hot" nodules. Nonfunctioning thyroid nodules, however, constitute a heterogeneous group that includes adenomas, cysts, subacute and chronic thyroiditis, multinodular goiter, various fibrotic, hemorrhagic and necrotic processes, in addition to thyroid neoplasia; cancer, indeed, accounts for only a minority of hypofunctioning or nonfunctioning nodules. Characterization of "cold" nodules to provide better discrimination between benign and malignant disorders has been attempted in several ways, including measurement of uptake of . . .
Cervical Screening at Age 50–64 Years and the Risk of Cervical Cancer at Age 65 Years and Older: Population-Based Case Control Study
Authors: Alejandra Castañón, Rebecca Landy, Jack Cuzick, Peter Sasieni
Journal: PLoS Medicine (2014)

Background There is little consensus, and minimal evidence, regarding the age at which to stop cervical screening. We studied the association between screening at age 50–64 y and cervical cancer at age 65–83 y. Methods and Findings Cases were women (n = 1,341) diagnosed with cervical cancer at age 65–83 y between 1 April 2007 and 31 March 2012 in England and Wales; age-matched controls (n = 2,646) were randomly selected from population registers. Screening details from 1988 onwards were extracted from national databases. We calculated the odds ratios (OR) for different screening histories and subsequent cervical cancer. Women with adequate negative screening at age 65 y (288 cases, 1,395 controls) were at lowest risk of cervical cancer (20-y risk: 8 cancers per 10,000 women) compared with those (532 cases, 429 controls) not screened at age 50–64 y (20-y risk: 49 cancers per 10,000 women, with OR = 0.16, 95% CI 0.13–0.19). ORs depended on the age mix of women because of the weakening association with time since last screen: OR = 0.11, 95% CI 0.08–0.14 at 2.5 to 7.5 y since last screen; OR = 0.27, 95% CI 0.20–0.36 at 12.5 to 17.5 y since last screen. Screening at least every 5.5 y between the ages 50 and 64 y was associated with a 75% lower risk of cervical cancer between the ages 65 and 79 y (OR = 0.25, 95% CI 0.21–0.30), and the attributable risk was such that in the absence of screening, cervical cancer rates in women aged 65+ would have been 2.4 (95% CI 2.1–2.7) times higher. In women aged 80–83 y the association was weaker (OR = 0.49, 95% CI 0.28–0.83) than in those aged 65–69 y (OR = 0.12, 95% CI 0.09–0.17). This study was limited by an absence of data on confounding factors; additionally, findings based on cytology may not generalise to human papillomavirus testing. Conclusions Women with adequate negative screening at age 50–64 y had one-sixth of the risk of cervical cancer at age 65–83 y compared with women who were not screened. Stopping screening between ages 60 and 69 y in women with adequate negative screening seems sensible, but further screening may be justifiable as life expectancy increases. Please see later in the article for the Editors' Summary
Vasopressin Gene Expression in Rats with Experimental Cirrhosis
Authors: Jin K. Kim, Sandra N. Summer, Randy L. Howard, Robert W. Schrier
Journal: Hepatology (1993)

Impaired ability to excrete a water load occurs in a substantial number of patients with advanced cirrhosis and in animals with experimental cirrhosis. The nonosmotic stimulation of arginine vasopressin release from the pituitary has been implicated as an important factor in the abnormal water excretion in patients and animals with cirrhosis. In this study, arginine vasopressin hypothalamic gene expression was studied in cirrhotic rats. Cirrhosis was induced by a combination of phenobarbital treatment in drinking water and weekly intragastric administration of carbon tetrachloride for 13 to 15 wk. Severe cirrhosis was confirmed by morphological analysis and the presence of ascites. Plasma arginine vasopressin was also significantly higher in rats with cirrhosis (control = 1.77 +/- 0.16 and cirrhotic rats = 4.14 +/- 0.62 pg/ml, n = 9, p < 0.002). Hypothalamic arginine vasopressin messenger RNA was also significantly higher in cirrhotic rats (control = 762.1 +/- 132.3 and cirrhotic rats = 1,834.2 +/- 271.9 pg/hypothalamus, n = 9, p < 0.005). Pituitary arginine vasopressin content was significantly lowered in cirrhotic rats (control = 3.69 +/- 0.98 and cirrhotic rats = 1.57 +/- 0.09 micrograms/pituitary, n = 9, p < 0.05). No difference was seen in hypothalamic arginine vasopressin content between the two groups (control = 4.64 +/- 0.34 and cirrhotic rats = 4.23 +/- 0.33 ng/hypothalamus, n = 9, NS). Oxytocin messenger RNA in the hypothalamus was also not significantly different between the two groups (control = 8.61 +/- 0.68 and cirrhotic rats = 9.33 +/- 0.65 unit of density, n = 9, NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Tissue Doppler predicts mortality and need for transplantation in children with dilated cardiomyopathy
Authors: Colin J. McMahon, Sherif Nagueh, Reanu Eapen, Irina Finkelshteyn, Louis I. Bezold, Xaoling Cao, Jack Price, William J. Dreyer, Jeffrey A. Towbin, Susan Denfield, Ricardo H. Pignatelli
Journal: Journal of the American College of Cardiology (2003)
Angiopoietin-1 Promotes Cardiac and Skeletal Myocyte Survival Through Integrins
Authors: Susan M. Dallabrida, Nesreen Ismail, Julianne R. Oberle, Blanca E. Himes, Maria A. Rupnick
Journal: Circulation Research (2005)

Cardiac myocyte loss, regardless of insult, can trigger compensatory myocardial remodeling leading to heart failure. Identifying mediators of cardiac myocyte survival may advance clinical efforts toward myocardial preservation. Angiopoietin-1 limits ischemia-induced cardiac injury. This benefit is ascribed to angiogenesis because the receptor, tie2, is largely endothelial-specific. We propose that direct, non-tie2 interactions of angiopoietin-1 on cardiac myocytes contribute to this cardioprotection. We found that mouse C2C12 skeletal myocytes lack tie2, yet dose-dependently adhered to angiopoietin-1 and angiopoietin-2 similarly to laminin, fibronectin, vitronectin, and more than to collagen-I, -III, and -IV. Adhesion was divalent cation-mediated (Mn2+, Ca2+, not Mg2+), blocked with EDTA/EGTA, RGD-based peptides, and select integrin subunit antibodies. Similar findings were obtained with human skeletal myocytes (HSMs) and freshly isolated rat neonatal cardiac myocytes (NCMs). Furthermore, angiopoietin-1 conferred significant survival advantage exceeding that of most cell matrices, which was not fully explained by differences in cell adhesion. Angiopoietin-1 promoted survival of serum-starved C2C12, HSM, and NCM (MTT, trypan blue) and prevented taxol-induced apoptosis (caspase-3). Immobilized and soluble angiopoietin-1 phosphorylated Akt(S473) and MAPK(p42/44), (not FAK(Y397)) in C2C12 more than in endothelial cells and more than did angiopoietin-2 or cell matrices. EDTA, RGD-based peptides, and some integrin antibodies blocked these responses. Angiopoietin-1 activated HSM and NCM Akt(S473) and MAPK(p42/44) survival pathways. We propose that this novel function contributes to developmental and cardioprotective actions of angiopoietin-1 presently attributed to vascular effects alone. Angiopoietin-1 may prove therapeutically valuable in cardiac remodeling by supporting myocyte viability and preserving pump function. The full text of this article is available online at http://circres.ahajournals.org.
Redesigning Primary Care
Authors: Thomas H. Lee, Thomas Bodenheimer, Allan H. Goroll, Barbara Starfield, Katharine Treadway
Journal: New England Journal of Medicine (2008)

U.S. primary care is in crisis. Primary care physicians must care for more and more patients, with more and more chronic conditions, in less and less time, for which they are compensated far less than subspecialists. They must absorb increasing volumes of medical information and complete more paperwork than ever, as they try to function in a poorly coordinated health care system. As a result, their ranks are thinning, with practicing physicians burning out and trainees shunning primary care fields. In a roundtable discussion moderated by Dr. Thomas Lee, four experts in primary care and related policy — Drs. Thomas . . .
Possible source of adenosine triphosphate released from rat myocytes in response to hypoxia and acidosis
Authors: C. A WILLIAMS, T. FORRESTER
Journal: Cardiovascular Research (1983)

Ventricular cells from adult rats were isolated enzymatically and used as a model system for determining what factors affect the release of adenosine triphosphate (ATP) from myocardial cells. The enzyme systems used to isolate cells were trypsin:collagenase; hya1uronidase:collagenase and dispase:collagenase. Adenosine triphosphate was released in greater amounts in response to hypoxia from cells freed by each of the enzymatic procedures. This occurred while the intracellular concentration of ATP remained constant. Experiments were then performed to determine whether the conditions that occur during myocardial ischaemia or hypoxia altered the release of ATP. Cells suspended in either oxygenated or anoxic buffer at a pH of 6.8 released a significantly lower amount of ATP than cells suspended in either condition at pH 7.4. To test the possibility that ATP was released from nucleotide-protein-Ca2+ complexes located in the sarcolemma, artificial disruption of these structures was carried out. Incubation of oxygenated cells with the chelating agent, ethyleneglycol-bis (B-aminoethyl ether)-N, N-tetraacetic acid (EGTA), stimulated the release of ATP in a hyperbolic relationship while incubation of anoxic cells with ethylenediamine tetraacetate (EDTA) stimulated the release of ATP in such a way that the pattern of release followed a sigmoid response with maximal amounts of ATP, 995±55 pmol·mg−2 protein, occurring in the presence of 0.1 to 2.0 mmol·litre−2 EDTA. By incubating cells with radioactive EDTA, there was no indication that EDTA entered the cells. No release of ATP above control levels occurred when EDTA was chelated with Ca2+ before being applied to isolated cells. These data suggest that the source of ATP found extracellularly may have been nucleotide-protein-Ca2+ complexes located in the sarcolemma, and further support the role of ATP as a coronary vasodilator during hypoxic conditions.
ColoPulse tablets perform comparably in healthy volunteers and Crohn's patients and show no influence of food and time of food intake on bioavailability
Authors: J.M. Maurer, R.C.A. Schellekens, H.M. van Rieke, F. Stellaard, K.D. Wutzke, D.J. Buurman, G. Dijkstra, H.J. Woerdenbag, H.W. Frijlink, J.G.W. Kosterink
Journal: Journal of Controlled Release (2013)
Rosacea and migraine.
Authors: S G Tan, W J Cunliffe
Journal: BMJ (1976)

information centres.Nevertheless, the onset of recovery was rapid.The important late effect of the poisoning was the development of jejunal ulceration and diverticula formation, and hence the formation of strictures remains a real possibility.The induction of a diuresis seemed to play a particularly important part in preventing acute renal damage.The prognosis in methylene chloride poisoning theh is far from hopeless.With scrupulous intensive care recovery may be anticipated.
Data Extraction Errors in Meta-analyses That Use Standardized Mean Differences
Authors: Peter C. Gøtzsche, Asbjørn Hróbjartsson, Katja Marić, Britta Tendal
Journal: JAMA (2007)

ContextMeta-analysis of trials that have used different continuous or rating scales to record outcomes of a similar nature requires sophisticated data handling and data transformation to a uniform scale, the standardized mean difference (SMD). It is not known how reliable such meta-analyses are.ObjectiveTo study whether SMDs in meta-analyses are accurate.Data SourcesSystematic review of meta-analyses published in 2004 that reported a result as an SMD, with no language restrictions. Two trials were randomly selected from each meta-analysis. We attempted to replicate the results in each meta-analysis by independently calculating SMD using Hedges adjusted g.Data ExtractionOur primary outcome was the proportion of meta-analyses for which our result differed from that of the authors by 0.1 or more, either for the point estimate or for its confidence interval, for at least 1 of the 2 selected trials. We chose 0.1 as cut point because many commonly used treatments have an effect of 0.1 to 0.5, compared with placebo.ResultsOf the 27 meta-analyses included in this study, we could not replicate the result for at least 1 of the 2 trials within 0.1 in 10 of the meta-analyses (37%), and in 4 cases, the discrepancy was 0.6 or more for the point estimate. Common problems were erroneous number of patients, means, standard deviations, and sign for the effect estimate. In total, 17 meta-analyses (63%) had errors for at least 1 of the 2 trials examined. For the 10 meta-analyses with errors of at least 0.1, we checked the data from all the trials and conducted our own meta-analysis, using the authors' methods. Seven of these 10 meta-analyses were erroneous (70%); 1 was subsequently retracted, and in 2 a significant difference disappeared or appeared.ConclusionsThe high proportion of meta-analyses based on SMDs that show errors indicates that although the statistical process is ostensibly simple, data extraction is particularly liable to errors that can negate or even reverse the findings of the study. This has implications for researchers and implies that all readers, including journal reviewers and policy makers, should approach such meta-analyses with caution.
Hypophyseal Influence on Function and Composition of Cardiac Muscle
Authors: William V. Whitehorn, Arthur F. Grimm, Theodore M. King
Journal: Circulation Research (1962)

The effects of hypophysectomy and of growth hormone (GH) on the properties and composition of rat myocardium were studied. GH, in dosage sufficient to maintain a normal rate of growth, did not correct the microcardia of hypophysectomy. Tension production of surviving left ventricular muscle columns was not modified by hypophysectomy or GH administration. Ventricular actomyosin concentration was slightly but significantly elevated in hypophysectomized animals, with or without GH. However, "ATP sensitivity" of the extracted actomyosin was markedly depressed by hypophysectomy and partially restored by GH. Differential hormonal regulation of cardiac actin and myosin is suggested.
A gripping case of peritoneal dialysis catheter malfunction
Authors: Peter A.G. Doubel, Franky P. Vansteenkiste, Olivier P. Schockaert
Journal: Kidney International (2015)

A 76-year-old woman with end-stage renal disease was started on peritoneal dialysis using a Swan neck–type catheter (Figure 1). After 1 week of successful peritoneal dialysis, major effluent problems arose. An abdominal X-ray showed the catheter tip being located correctly in the minor pelvis. Empiric attempts to restore catheter function with laxatives and intra-catheter instillation of urokinase failed to improve the effluent flows. A relook laparoscopy showed impingement of the catheter orifices by fimbriae of the right fallopian tube. The catheter was subsequently surgically unobstructed and fixed medially to the anterior abdominal wall, whereas the right ovarium was fixed laterally in the right iliac fossa. Two weeks later, peritoneal dialysis was resumed without any further catheter problems. Obstruction of the peritoneal dialysis catheter by fallopian tube fimbriae is a rare cause of catheter dysfunction, the more frequent causes being catheter tip migration, entrapment by an omental wrap, or small bowel and fibrin clotting.
Prospective study of skin surgery in smokers vs. nonsmokers
Authors: A.J. Dixon, M.P. Dixon, J.B. Dixon, C.B. Del Mar
Journal: British Journal of Dermatology (2008)

Smoking may increase complications following minor surgery leading many clinicians to urge patients to refrain from smoking before and after surgery.To study the association between smoking and complications following skin surgery.In a 5-year prospective observational study 7224 lesions were excised on 4197 patients. Patients were not instructed regarding smoking. All complications were recorded.A total of 439 smokers (10.5%) underwent 646 procedures (9%), 3758 nonsmokers (89.5%) underwent 6578 procedures (91%). Smokers were younger (55 +/- 16 years) than nonsmokers (66 +/- 17 years) (P < 0.001). Infection incidence was not significantly different, 1.9% (12/646) in smokers compared with 2.2% (146/6578) in nonsmokers (P = 0.55). There were two bleeds with smokers (0.3%) vs. 50 in nonsmokers (0.8%) (P = 0.2). The incidence of wound dehiscence in nonsmokers (three) was not different from nonsmokers (21) (P = 0.54). However, the incidence of scar contour distortion in smokers (three) was greater than in nonsmokers (two) (odds ratio 15.3; 95% confidence interval 2.5-92). Total complication incidence was similar, 3.6% in smokers vs. 4.0% in nonsmokers (P = 0.58). Out of 2371 flaps there were 14 (0.6%) cases of end-flap necrosis but smokers were not at increased risk. The case-control analysis compared each smoker with two nonsmokers matched for age, sex, postal code and outdoor occupational exposure. This again demonstrated no difference in infection, scar complication, bleed, dehiscence, end-flap necrosis or total complication incidence.Smokers and nonsmokers suffer skin surgery complications similarly. The increased risk of contour distortion identified was difficult to interpret. Advice to cease smoking in the short term to improve outcomes with skin cancer surgery is not supported by these data.
THE THERAPEUTIC VALUE OF DIGITALIS IN PNEUMONIA
Authors: JOHN WYCKOFF
Journal: JAMA (1930)

The work of Cohn and Jamieson<sup>1</sup>definitely established that there is a digitalis action on the heart in lobar pneumonia. In an address given in 1916 on the use of digitalis in pneumonia, Cohn<sup>2</sup>concluded that this drug did no harm and might be life saving. He suggested that it might be given to all patients as a routine, and explained the method of dosage in operation at the Hospital of the Rockefeller Institute. This extremely careful work and these conservative suggestions naturally influenced medical thought throughout the country, so that during the next ten years the routine giving of digitalis to patients with lobar pneumonia became a not uncommon procedure in many clinics, including Bellevue Hospital and most of the other large hospitals in New York. However, during the period in which digitalis was given, no studies of comparative mortality were made between groups of patients with
The RANTES promoter polymorphism: A genetic risk factor for near-fatal asthma in Chinese children
Authors: Tsung-Chieh Yao, Ming-Ling Kuo, Lai-Chu See, Li-Chen Chen, Dah-Chin Yan, Liang-Shiou Ou, Cheng-Kuang Shaw, Jing-Long Huang
Journal: Journal of Allergy and Clinical Immunology (2003)