tbuckley/cabot-search huggingface dataset:
Genetic signatures of High- and Low-Risk Aberrant Crypt Foci in a Mouse Model of Sporadic Colon Cancer
Authors: Prashant R. Nambiar, Masako Nakanishi, Rishi Gupta, Evelyn Cheung, Ali Firouzi, Xiao-Jun Ma, Christopher Flynn, Mei Dong, Kishore Guda, Joel Levine, Rajiv Raja, Luke Achenie, Daniel W. Rosenberg
Journal: Cancer Research (2004)

Abstract To determine whether cancer risk is related to histopathological features of preneoplastic aberrant crypt foci (ACF), gene expression analysis was performed on ACF from two mouse strains with differing tumor sensitivity to the colonotropic carcinogen, azoxymethane. ACF from sensitive A/J mice were considered at high risk, whereas ACF from resistant AKR/J mice were considered at low risk for tumorigenesis. A/J and AKR/J mice received weekly injections of azoxymethane (10 mg/kg body weight), and frozen colon sections were prepared 6 weeks later. Immunohistochemistry was performed using biomarkers associated with colon cancer, including adenomatous polyposis coli, β-catenin, p53, c-myc, cyclin D1, and proliferating cell nuclear antigen. Hyperplastic ACF, dysplastic ACF, microadenomas, adjacent normal-appearing epithelium, and vehicle-treated colons were laser captured, and RNA was linearly amplified (LCM-LA) and subjected to cDNA microarray-based expression analysis. Patterns of gene expression were identified using adaptive centroid algorithm. ACF from low- and high-risk colons were not discriminated by immunohistochemistry, with the exception of membrane staining of β-catenin. To develop genetic signatures that predict cancer risk, LCM-LA RNA from ACF was hybridized to cDNA arrays. Of 4896 interrogated genes, 220 clustered into six broad clusters. A total of 226 and 202 genes was consistently altered in lesions from A/J and AKR/J mice, respectively. Although many alterations were common to both strains, expression profiles stratified high- and low- risk lesions. These data demonstrate that ACF with distinct tumorigenic potential have distinguishing molecular features. In addition to providing insight into colon cancer promotion, our data identify potential biomarkers for determining colon cancer risk in humans.
Diuretic Resistance versus Adaptation
Authors: Jacob Zatuchni
Journal: Annals of Internal Medicine (1991)

Letters1 September 1991Diuretic Resistance versus AdaptationJacob Zatuchni, MDJacob Zatuchni, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-115-5-408 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors:Ellison (1), in his excellent study of diuretic resistance, does not consider its most common occurrence—the absence of diuresis with continued administration of a diuretic to a person with heart disease but whose heart failure has been dissipated. In the treatment of heart failure, continued daily administration of a diuretic is common practice to prevent recurrence of edema, attainment of dry weight notwithstanding. In such a circumstance, the body is resistant to the diuretic. The diuretic drug becomes paradoxically not only a salt-retaining agent, but also a stimulator of potentially noxious neurohormones. With subsidence or control of...References1. Ellison D. The physiologic basis of diuretic synergism: its role in treating diuretic resistance. Ann Intern Med. 1991;114:886-94. LinkGoogle Scholar2. Zatuchni J. The treatment of congestive heart failure with diuretics and nondiuretic agents. Clin Ther. 1988;10:327-49. Google Scholar1. Ellison D. The physiologic basis of diuretic synergism: its role in treating diuretic resistance. Ann Intern Med. 1991;114:886-94. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Pennsylvania Hospital Philadelphia, PA 19107 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1991Volume 115, Issue 5Page: 408-409KeywordsCardiovascular therapyDiureticsDrugsEdemaHeart failureLongitudinal studies Issue Published: 1 September 1991 PDF DownloadLoading ...
Autosplenectomy: rare syndrome in autoimmunopathy
Authors: J Leipe, A J Hueber, S Kallert, J Rech, H Schulze-Koops
Journal: Annals of the Rheumatic Diseases (2006)

Autosplenectomy has been described in association with systemic lupus erythematosus (SLE).1 Although in patients with SLE small or atrophic spleens are usually seen, the complete absence of the spleen has been observed rarely. Here, we report a patient with an 18-year history of autoimmunopathy who developed anatomical asplenia during the disease.

A 51-year-old Caucasian woman was first diagnosed in 1988 as having autoimmunopathy of incompletely defined aetiology with antinuclear antibodies (ANA) positivity and immunocomplexes in conjunction with reduced complement levels and serositis. The patient presented with massive pleural and pericardial effusions. Laboratory studies showed normal blood counts. Antibodies to extractable nuclear antigens or to phospholipids (lupus anticoagulant and anti-cardiolipin antibodies) could not be detected. Although suggestive of having SLE, the patient …
The effect of histamine H2-receptor blockade with metiamide on serum gastrin levels in man.
Authors: G O Barbezat, B Grant, S Bank, A Vinik
Journal: Gut (1975)

Metiamide, an histamine H2-receptor antagonist which inhibits gastric acid secretion, does not lower basal serum gastrin concentration in man. Serum gastrin responses after stimulation by food were marginally higher when the stimulus of food was preceded by metiamide.
HIV, hepatitis B virus, and hepatitis C virus co-infection in patients in the China National Free Antiretroviral Treatment Program, 2010–12: a retrospective observational cohort study
Authors: Fujie Zhang, Hao Zhu, Yasong Wu, Zhihui Dou, Yao Zhang, Nora Kleinman, Marc Bulterys, Zunyou Wu, Ye Ma, Decai Zhao, Xia Liu, Hua Fang, Jing Liu, Wei-Ping Cai, Hong Shang
Journal: The Lancet Infectious Diseases (2014)
Crosstalk between Glioma-Initiating Cells and Endothelial Cells Drives Tumor Progression
Authors: Hye-Min Jeon, Sung-Hak Kim, Xun Jin, Jong Bae Park, Se Hoon Kim, Kaushal Joshi, Ichiro Nakano, Hyunggee Kim
Journal: Cancer Research (2014)

Abstract Glioma-initiating cells (GIC), which reside within the perivascular microenvironment to maintain self-renewal capacity, are responsible for glioblastoma initiation, progression, and recurrence. However, the molecular mechanisms controlling crosstalk between GICs and endothelial cells are poorly understood. Here, we report that, in both GICs and endothelial cells, platelet-derived growth factor (PDGF)–driven activation of nitric oxide (NO) synthase increases NO-dependent inhibitor of differentiation 4 (ID4) expression, which in turn promotes JAGGED1–NOTCH activity through suppression of miR129 that specifically represses JAGGED1 suppression. This signaling axis promotes tumor progression along with increased GIC self-renewal and growth of tumor vasculature in the xenograft tumors, which is dramatically suppressed by NOTCH inhibitor. ID4 levels correlate positively with NOS2 (NO synthase-2), HES1, and HEY1 and negatively with miR129 in primary GICs. Thus, targeting the PDGF–NOS–ID4–miR129 axis and NOTCH activity in the perivascular microenvironment might serve as an efficacious therapeutic modality for glioblastoma. Cancer Res; 74(16); 4482–92. ©2014 AACR.
Cardiac T2* Magnetic Resonance for Prediction of Cardiac Complications in Thalassemia Major
Authors: P. Kirk, M. Roughton, J.B. Porter, J.M. Walker, M.A. Tanner, J. Patel, D. Wu, J. Taylor, M.A. Westwood, L.J. Anderson, D.J. Pennell
Journal: Circulation (2009)

Background— The goal of this study was to determine the predictive value of cardiac T2* magnetic resonance for heart failure and arrhythmia in thalassemia major. Methods and Results— We analyzed cardiac and liver T2* magnetic resonance and serum ferritin in 652 thalassemia major patients from 21 UK centers with 1442 magnetic resonance scans. The relative risk for heart failure with cardiac T2* values &lt;10 ms (compared with &gt;10 ms) was 160 (95% confidence interval, 39 to 653). Heart failure occurred in 47% of patients within 1 year of a cardiac T2* &lt;6 ms with a relative risk of 270 (95% confidence interval, 64 to 1129). The area under the receiver-operating characteristic curve for predicting heart failure was significantly greater for cardiac T2* (0.948) than for liver T2* (0.589; P &lt;0.001) or serum ferritin (0.629; P &lt;0.001). Cardiac T2* was &lt;10 ms in 98% of scans in patients who developed heart failure. The relative risk for arrhythmia with cardiac T2* values &lt;20 ms (compared with &gt;20 ms) was 4.6 (95% confidence interval, 2.66 to 7.95). Arrhythmia occurred in 14% of patients within 1 year of a cardiac T2* of &lt;6 ms. The area under the receiver-operating characteristic curve for predicting arrhythmia was significantly greater for cardiac T2* (0.747) than for liver T2* (0.514; P &lt;0.001) or serum ferritin (0.518; P &lt;0.001). The cardiac T2* was &lt;20 ms in 83% of scans in patients who developed arrhythmia. Conclusions— Cardiac T2* magnetic resonance identifies patients at high risk of heart failure and arrhythmia from myocardial siderosis in thalassemia major and is superior to serum ferritin and liver iron. Using cardiac T2* for the early identification and treatment of patients at risk is a logical means of reducing the high burden of cardiac mortality in myocardial siderosis. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00520559.
Elimination Half-Life of Drugs: Value and Limitations
Authors: D J Greenblatt
Journal: Annual Review of Medicine (1985)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Personalizing Mammography by Breast Density and Other Risk Factors for Breast Cancer: Analysis of Health Benefits and Cost-Effectiveness
Authors: John T. Schousboe, Karla Kerlikowske, Andrew Loh, Steven R. Cummings
Journal: Annals of Internal Medicine (2011)

Background: Current guidelines recommend mammography every 1 or 2 years starting at age 40 or 50 years, regardless of individual risk for breast cancer. Objective: To estimate the cost-effectiveness of mammography by age, breast density, history of breast biopsy, family history of breast cancer, and screening interval. Design: Markov microsimulation model. Data Sources: Surveillance, Epidemiology, and End Results program, Breast Cancer Surveillance Consortium, and the medical literature. Target Population: U.S. women aged 40 to 49, 50 to 59, 60 to 69, and 70 to 79 years with initial mammography at age 40 years and breast density of Breast Imaging Reporting and Data System (BI-RADS) categories 1 to 4. Time Horizon: Lifetime. Perspective: National health payer. Intervention: Mammography annually, biennially, or every 3 to 4 years or no mammography. Outcome Measures: Costs per quality-adjusted life-year (QALY) gained and number of women screened over 10 years to prevent 1 death from breast cancer. Results of Base-Case Analysis: Biennial mammography cost less than $100 000 per QALY gained for women aged 40 to 79 years with BI-RADS category 3 or 4 breast density or aged 50 to 69 years with category 2 density; women aged 60 to 79 years with category 1 density and either a family history of breast cancer or a previous breast biopsy; and all women aged 40 to 79 years with both a family history of breast cancer and a previous breast biopsy, regardless of breast density. Biennial mammography cost less than $50 000 per QALY gained for women aged 40 to 49 years with category 3 or 4 breast density and either a previous breast biopsy or a family history of breast cancer. Annual mammography was not cost-effective for any group, regardless of age or breast density. Results of Sensitivity Analysis: Mammography is expensive if the disutility of false-positive mammography results and the costs of detecting nonprogressive and nonlethal invasive cancer are considered. Limitation: Results are not applicable to carriers of BRCA1 or BRCA2 mutations. Conclusion: Mammography screening should be personalized on the basis of a woman's age, breast density, history of breast biopsy, family history of breast cancer, and beliefs about the potential benefit and harms of screening. Primary Funding Source: Eli Lilly, Da Costa Family Foundation for Research in Breast Cancer Prevention of the California Pacific Medical Center, and Breast Cancer Surveillance Consortium.
Hepatitis B virus infection and risk of intrahepatic cholangiocarcinoma and non-Hodgkin lymphoma: A cohort study of parous women in Taiwan
Authors: Chyng-Wen Fwu, Yin-Chu Chien, San-Lin You, Kenrad E. Nelson, Gregory D. Kirk, Hsu-Sung Kuo, Manning Feinleib, Chien-Jen Chen
Journal: Hepatology (2011)

Few studies have evaluated the risk of cancers other than hepatocellular carcinoma associated with hepatitis B virus (HBV) infection. This study aimed to estimate incidence rates of intrahepatic cholangiocarcinoma (ICC) and non-Hodgkin lymphoma (NHL) and its major subtypes in a nationwide cohort of parous women and to assess their associations with chronic HBV infection. We conducted a cohort study including 1,782,401 pregnant Taiwanese women whose HBV serostatus was obtained from the National Hepatitis B Vaccination Registry. Newly diagnosed ICCs and NHLs were ascertained through data linkage with the National Cancer Registry. Risks of ICC and NHL were assessed using Cox proportional hazards regression models. After a mean of 6.91 years of follow-up, there were 18 cases of ICC and 192 cases of NHL, including 99 cases of diffuse large B-cell lymphoma (DLBCL). Incidence rates of ICC were 0.09 and 0.43 per 100,000 person-years, respectively, among women who were hepatitis B surface antigen (HBsAg)-seronegative and HBsAg-seropositive, showing an age-adjusted hazard ratio (HRadj) (95% confidence interval [CI]) of 4.80 (1.88-12.20). The incidence rates of NHL overall for HBsAg-seronegative and HBsAg-seropositive women were 1.23 and 3.18 per 100,000 person-years, respectively, with an HRadj (95% CI) of 2.63 (1.95-3.54). Among NHL subtypes, HBsAg-seropositive women had an increased risk of DLBCL compared with those who were HBsAg-seronegative (incidence rates: 1.81 and 0.60 per 100,000 person-years, respectively; HRadj [95% CI]: 3.09 [2.06-4.64]). The significantly increased risk was not observed for other specific subtypes of NHL. Conclusions: Chronic HBV infection was associated with an increased risk of ICC and DLBCL in women. Our data suggested a possible etiological role of HBV in the development of ICC and specific subtypes of NHL. (HEPATOLOGY 2011;)
Photosensitizer-Conjugated Gold Nanorods for Enzyme-Activatable Fluorescence Imaging and Photodynamic Therapy
Authors: Boseung Jang, Yongdoo Choi
Journal: Theranostics (2012)

We report on the development of photosensitizer-conjugated gold nanorods (MMP2P-GNR) in which photosensitizers were conjugated onto the surface of gold nanorods (GNR) via a protease-cleavable peptide linker. We hypothesized that fluorescence and phototoxicity of the conjugated photosensitizers would be suppressed in their native state, becoming activated only after cleavage by the target protease matrix metalloprotease-2 (MMP2). Quantitative analysis of the fluorescence and singlet oxygen generation (SOG) demonstrated that the MMP2P-GNR conjugate emitted fluorescence intensity corresponding to 0.4% ± 0.01% and an SOG efficiency of 0.89% ± 1.04% compared to free pyropheophorbide-a. From the in vitro cell studies using HT1080 cells that overexpress MMP2 and BT20 cells that lack MMP2, we observed that fluorescence and SOG was mediated by the presence or absence of MMP2 in these cell lines. This novel activatable photosensitizing system may be useful for protease-mediated fluorescence imaging and subsequent photodynamic therapy for various cancers.
Medically unexplained physical symptoms in medical practice: a psychiatric perspective.
Authors: Javier I Escobar, Constanza Hoyos-Nervi, Michael Gara
Journal: Environmental Health Perspectives (2002)

Clusters of medically unexplained physical symptoms have been referred to in the literature by many different labels, including somatization, symptom-based conditions, and functional somatic syndromes, among many others. The traditional medical perspective has been to classify and study these symptoms and functional syndromes separately. In psychiatry, current taxonomies (Diagnostic and Statistical Manual of Mental Disorder, 4th edition, and The International Statistical Classification of Diseases and Related Health Problems, 10th revision) classify these syndromes together under the rubric of somatoform disorders. In this article we approach medically unexplained physical symptoms from a psychiatric perspective and discuss the common features that unite multiple unexplained symptoms or functional somatic syndromes as a class. Included in this article is a discussion of nosological issues, clinical assessment, how these syndromes are viewed within the various medical specialties, and clinical management and treatment.
Lung Deposition of Inhaled Drugs Increases with Age
Authors: JACOB ANH ØJ, LARS THORSSON, HANS BISGAARD
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Budesonide plasma concentrations after inhalation of a fixed dose of the drug from a pressurized metered dose inhaler (pMDI) with spacer (Nebuchamber) were compared in young children and adults: 26 patients with mild asthma comprising 8 children 2–3 yr, 8 children 4–6 yr, and 10 adults 20–41 yr. Budesonide 2 × 200 μ g was given by pMDI via Nebuchamber with mouthpiece and noseclip. Children of 2–3 yr used a facemask. Plasma was collected regularly for 8 h after drug administration. Budesonide was measured by liquid chromatography plus tandem mass spectrometry. The dose to patient was estimated as the dose of budesonide delivered from the pMDI with adapter minus the amount of budesonide recovered from the spacer, facemask, or mouthpiece, mouth rinse, and facial skin. The systemic exposure was estimated from the plasma concentration and expressed as the area under the curve of plasma concentration versus time (AUC). Terminal half-life (T1/2) was evaluated. Dose to patient, AUC, and T1/2 were similar in the three age groups (p > 0.35). Nebuchamber delivers the same dose of budesonide to young children and adults. Yet the plasma concentration of budesonide was similar in young children and adults. Therefore, lung dose is increased with age. This suggests that from a safety perspective, the prescribed dose of budesonide inhaled from a pMDI with Nebuchamber spacer need not be adjusted for age or use of facemask. Children and adults can use the same nominal dose of budesonide via Nebuchamber as adults without an increased risk of systemic exposure.
Effect of Epidermal Growth Factor Receptor Inhibitor Class in the Treatment of Head and Neck Cancer with Concurrent Radiochemotherapy <i>In vivo</i>
Authors: Felix Y. Feng, Carlos A. Lopez, Daniel P. Normolle, Sooryanarayana Varambally, Xiaoxin Li, Patrick Y. Chun, Mary A. Davis, Theodore S. Lawrence, Mukesh K. Nyati
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To optimally integrate epidermal growth factor receptor (EGFR) inhibitors into the clinical treatment of head and neck cancer, two important questions must be answered: (a) does EGFR inhibition add to the effects of radiochemotherapy, and (b) if so, which method of inhibiting EGFR is superior (an EGFR antibody versus a small molecule tyrosine kinase inhibitor)? We designed an in vivo study to address these questions. Experimental Design: Nude mice with UMSCC-1 head and neck cancer xenografts received either single, double, or triple agent therapy with an EGFR inhibitor (either cetuximab or gefitinib), gemcitabine, and/or radiation for 3 weeks. Tumor volumes and animal weights were measured for up to 15 weeks. Immunoblotting and immunofluorescent staining were done on tumors treated with either cetuximab or gefitinib alone. Results: The addition of an EGFR inhibitor significantly delayed the tumor volume doubling time, from a median of 40 days with radiochemotherapy (gemcitabine and radiation) alone, to 106 days with cetuximab and 66 days with gefitinib (both P &amp;lt; 0.005). Cetuximab resulted in significantly less weight loss than gefitinib. Immunoblot analysis and immunofluorescent staining of tumors show that although levels of phosphorylated AKT and extracellular signal–regulated kinase were decreased similarly in response to cetuximab or gefitinib, cetuximab caused prolonged suppression of pEGFR, pSTAT3, and BclXL compared with gefitinib. Conclusions: EGFR inhibition, particularly with cetuximab, improves the effectiveness of radiochemotherapy in this model of head and neck cancer. The correlation of response with prolonged suppression of EGFR, STAT3, and BclXL offers the possibility that these may be candidate biomarkers for response.
Global threat from drug resistant HIV in sub-Saharan Africa
Authors: R. L. Hamers, C. Kityo, J. M. A. Lange, T. F. R. d. Wit, P. Mugyenyi
Journal: BMJ (2012)

Roll-out of antiretroviral treatment for HIV in sub-Saharan Africa has been accompanied by rising rates of drug resistance. <b>Raph Hamers and colleagues</b> call for improved patient management and the integration of population based drug resistance surveillance into national treatment programmes
Rapid diagnosis of pyrazinamide-resistant multidrug-resistant tuberculosis using a molecular-based diagnostic algorithm
Authors: S.O. Simons, T. van der Laan, A. Mulder, J. van Ingen, L. Rigouts, P.N.R. Dekhuijzen, M.J. Boeree, D. van Soolingen
Journal: Clinical Microbiology and Infection (2014)
Remarks on Cremation or Burial?
Authors: T. S. Wells
Journal: BMJ (1880)

country; and their health ought to be, if not the first, at any rate one of the first considerations of a statesman.Now we 'have been moving REMARKS ~~~~~~~~gradually in the direction of these views, and there has been for some ON years a notion, soon about to amount, I believe, to a conviction, that the institution of churchyards is one which is highly prejudicial to the CR EM AT I10N 0OR B URI AL? * public health.I think'it would be amuchwiserstep if wewereto say that the time has arrived, seeing the vast increase of p)opulation in this By T. SPE N C ER WVE L LS, country and the increase which we miay contemplate, whien we should Vice-President of the Royal College of Surgeons; Surgeon to the Queen's close all these churchyards, and when we should take steps for farniish-