tbuckley/cabot-search huggingface dataset:
Infective Endocarditis in Childhood: 2015 Update
Authors: Robert S. Baltimore, Michael Gewitz, Larry M. Baddour, Lee B. Beerman, Mary Anne Jackson, Peter B. Lockhart, Elfriede Pahl, Gordon E. Schutze, Stanford T. Shulman, Rodney Willoughby
Journal: Circulation (2015)

Epidemiology and Clinical Findings of IE in ChildrenIn a previous report, IE occurred less often in children than in adults and accounted for approximately 1 in 1280 (0.78 per 1000) pediatric admissions per year from 1972 to 1982 at a referral insitution. 4In a recent multicenter report, 5 the annual incidence rate in the United States was between approximately 0.05 and 0.12 cases per 1000 pediatric admissions from 2003 to 2010, without a significant trend.][7][8] This may be related to improved survival among children who are at risk for endocarditis, such as those with CHD (with or without surgery) and hospitalized newborn infants.
Serologic and Clinical Outcomes of 1536 Alaska Natives Chronically Infected with Hepatitis B Virus
Authors: Brian J. McMahon, Peter Holck, Lisa Bulkow, Mary Snowball
Journal: Annals of Internal Medicine (2001)

Background: Knowledge of the outcome of chronic hepatitis B virus (HBV) infection is limited. Objective: To determine the incidence of and risk factors for adverse events (hepatocellular carcinoma and end-stage liver disease) and clearance of hepatitis B e antigen (HBeAg) and surface antigen (HBsAg) in carriers of HBV. Design: Population-based cohort study of hepatitis B carriers who were observed for a median of 12.3 years as part of an active surveillance program to detect carriers with hepatocellular carcinoma. Setting: 126 communities in Alaska. Patients: 1536 Alaska Natives with chronic hepatitis B. Measurements: Bivariate comparisons, multivariable models, and other statistical methods were used to examine the relationships of risk factors to outcomes and clearance of HBeAg and HBsAg. Results: 1536 chronic HBV carriers were followed up for 19 430 person-years from their first HBsAg-positive test result. At the first serologic test, 641 were HBeAg positive and 893 were anti-HBe positive. Older carriers were more likely than younger carriers to clear HBeAg (P < 0.001). The observed probability of clearing HBeAg within 10 years of diagnosis was 72.5%. Clearance of HBsAg occurred in 106 (7%) of all carriers and was positively associated with older age and positive result on initial anti-HBe test. The incidence of adverse events was 2.3 per 1000 carrier-years, and the incidence of hepatocellular carcinoma was 1.9 per 1000 carrier-years (2.3 in men and 1.2 in women). Risk for hepatocellular carcinoma increased with age, among those of Yupik Eskimo ethnicity, and among carriers who reverted from anti-HBe to HBeAg. Conclusion: In HBsAg-positive carriers, observed clearance of HBeAg was more than 70% during the first 10 years of follow-up.
Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes.
Authors: E P Sampaio, E N Sarno, R Galilly, Z A Cohn, G Kaplan
Journal: The Journal of Experimental Medicine (1991)

Thalidomide selectively inhibits the production of human monocyte tumor necrosis factor alpha (TNF-alpha) when these cells are triggered with lipopolysaccharide and other agonists in culture. 40% inhibition occurs at the clinically achievable dose of the drug of 1 micrograms/ml. In contrast, the amount of total protein and individual proteins labeled with [35S]methionine and expressed on SDS-PAGE are not influenced. The amounts of interleukin 1 beta (IL-1 beta), IL-6, and granulocyte/macrophage colony-stimulating factor produced by monocytes remain unaltered. The selectivity of this drug may be useful in determining the role of TNF-alpha in vivo and modulating its toxic effects in a clinical setting.
Retinal Detachment Centres
Authors: T. S.-B. Kelly
Journal: BMJ (1965)

of cancer in a cell (of the system under study) is G(t) and that there are n cells " at risk."On the usual independence assumption we may then deduce the probability distri- bution function of age of appearance of the disease in the individual as3 4The age-specific incidence of the disease at age t will then be f(t)/ {1 -F(t)}, where f(t) = dF(t)/dt.For large n, F(t) will be virtually determined by the structure of G(t) as G(t)->O.3This can be shown to imply that any g(t)[ =dG(t)/dt] which behaves as a power of t for small G(t) will produce the known age-specific incidence pattern.3For example, both the following g(t)'s will produce the required age-specific incidence pattern:(I) g(t) =e-At Ar tr-1/(r-l)!(2)(1) is the model of r somatic mutations re- quired in any order within a single cell where the mutations occur at a constant rate A per cell per year, and (2) is the well-known F distribution on vi and V2 degrees of freedom.We carry no torch for any particular alter- native theory but wish only to point out that no theory of carcinogenesis can be considered to be established solely on the basis of the mathematical relationship between incidence rates and age.-Weare, etc.,
Frequency of application of topical corticosteroids: an overview
Authors: None Lagos, None Maibach
Journal: British Journal of Dermatology (1998)

The frequency of application of topical corticosteroids has remained an unresolved issue through the decades with most textbooks and physicians recommending multiple daily use. This review focuses on the rationale of once daily application of corticoids as an effective treatment in some patients. Dermatopharmacokinetic data relevant to the dosage and frequency of application of topical corticoids are discussed. Clinical trials on the efficacy of once daily vs. twice daily applications are evaluated.
A Learning Health Care System for Pediatrics
Authors: William Gardner, Kelly Kelleher
Journal: JAMA Pediatrics (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Incidence of bullous pemphigoid and mortality of patients with bullous pemphigoid in Olmsted County, Minnesota, 1960 through 2009
Authors: Katherine E. Brick, Chad H. Weaver, Christine M. Lohse, Mark R. Pittelkow, Julia S. Lehman, Michael J. Camilleri, Mustafa Al-Hashimi, Carilyn N. Wieland
Journal: Journal of the American Academy of Dermatology (2014)
Culture of oocytes and risk of imprinting defects
Authors: Ellen Anckaert, Martine De Rycke, Johan Smitz
Journal: Human Reproduction Update (2012)

Follicle culture and oocyte in vitro maturation (IVM) are emerging assisted reproductive technologies with potentially important future applications in the fertility clinic. There is concern that these technologies might interfere at the epigenetic level and, in particular, with genomic imprinting. The timely acquisition of correct imprinting patterns in oocytes and the maintenance of genomic imprinting after fertilization are both required for normal embryonic development. A systematic literature search in Pubmed was performed and all publications reporting on the effects of follicle culture, IVM or ovarian tissue culture on genomic imprinting were retained. Mouse ovarian tissue culture studies, mouse in vitro follicle culture studies and a single bovine IVM study generally showed correct imprinted DNA methylation establishment in oocytes. Influences of treatment and suboptimal culture conditions in mouse follicle culture indicate that imprinting establishment in oocytes is a robust process. This is in contrast with preimplantation embryo culture-induced epigenetic defects reported in mice. For human IVM, no definitive conclusion on imprinting establishment can be drawn as well-designed studies are currently not available. Animal models provide reassuring data on imprinting establishment in cultured oocytes, but further studies should assess the effect of oocyte culture on imprinting maintenance. Optimized IVM procedures should be assessed in well-designed human studies. Finally, epigenetic analysis should be performed in children born from pregnancies after IVM to draw definitive conclusions on the epigenetic safety of human IVM.
Bortezomib Inhibits Nuclear Factor-κB–Dependent Survival and Has Potent <i>In vivo</i> Activity in Mesothelioma
Authors: Andrea Sartore-Bianchi, Fabio Gasparri, Arturo Galvani, Linda Nici, James W. Darnowski, Dario Barbone, Dean A. Fennell, Giovanni Gaudino, Camillo Porta, Luciano Mutti
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Purpose of this study has been the assessment of nuclear factor-κB (NF-κB) as a survival factor in human mesothelial cells (HMC), transformed HMC and malignant mesothelioma (MMe) cells. We aimed at verifying whether the proteasome inhibitor Bortezomib could abrogate NF-κB activity in MMe cells, leading to tumor cell death and may be established as a novel treatment for this aggressive neoplasm. Experimental Design: In HMC and MMe cells, NF-κB nuclear translocation and DNA binding were studied by electrophoretic mobility shift assay, following treatment with tumor necrosis factor-α (TNF-α). The IKK inhibitor Bay11-7082 was also tested to evaluate its effects on HMC, transformed HMC, and MMe cell viability upon exposure to asbestos fibers. Following Bortezomib treatment, cytotoxicity of MMe cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, whereas apoptosis and cell-cycle blockade were investigated by high-content analysis. Bortezomib was also given to mice bearing i.p. xenografts of MMe cells, and its effects on tumor growth were evaluated. Results: Here, we show that NF-κB activity is a constitutive survival factor in transformed HMC, MMe cells, and acts as a survival factor in HMC exposed to asbestos fibers. Bortezomib inhibits NF-κB activity in MMe cells and induces cell cycle blockade and apoptosis in vitro as well as tumor growth inhibition in vivo. Conclusions: Inhibition of NF-κB constitutive activation in MMe cells by Bortezomib resulted in in vitro cytotoxicity along with apoptosis and in vivo tumor regression. Our results support the use of Bortezomib in the treatment of MMe and has led to a phase II clinical trial currently enrolling in Europe.
A STUDY OF A GENERALIZED ERUPTION CAUSED BY MICROSPORON AUDOUINI—LICHEN MICROSPORICUS.*
Authors: CLARK W. FINNERUD
Journal: British Journal of Dermatology (1925)

Journal Article A STUDY OF A GENERALIZED ERUPTION CAUSED BY MICROSPORON AUDOUINI—LICHEN MICROSPORICUS. Get access CLARK W. FINNERUD, S.B., M.D. CLARK W. FINNERUD, S.B., M.D. Clinical Instructor of Dermatology in Rush Medical College, University of Chicago. (Chicago, Illinois.) Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 37, Issue 2, 1 February 1925, Pages 63–83, https://doi.org/10.1111/j.1365-2133.1925.tb09927.x Published: 01 February 1925
Ca2+ dependence of alpha-adrenergic effects on the contractile properties and Ca2+ homeostasis of cardiac myocytes.
Authors: M C Capogrossi, W A Kachadorian, G Gambassi, H A Spurgeon, E G Lakatta
Journal: Circulation Research (1991)

alpha-Adrenergic stimulation is known to enhance myocardial contractility. Adult rat left ventricular myocytes bathed in 1 mM [Ca2+] (Ca0) and electrically stimulated at 0.2 Hz responded to alpha-adrenergic stimulation with 50 microM phenylephrine and 1 microM propranolol with an increase in twitch amplitude to 177.1 +/- 25.6% of control (mean +/- SEM). In contrast, when cell Ca2+ loading was increased by bathing cells in 5 mM Ca0, alpha-adrenergic stimulation decreased twitch amplitude to 68.6 +/- 8.2% of control. Time-averaged cytosolic [Ca2+] of cells in 1.0 mM Ca0 is enhanced via an increase in the frequency of electrical stimulation. When myocytes were stimulated at 2 Hz in 1 mM Ca0, alpha-adrenergic stimulation did not increase twitch amplitude (103.8 +/- 12.4% of control). In myocytes loaded with the Ca2+ probe into-1, alpha-adrenergic effects during stimulation at 0.2 Hz (an increase in twitch amplitude in 1 mM Ca0 and a decrease in twitch amplitude in 5 mM Ca0) were associated with similar changes in the indo-1 transient. In 5 mM Ca0, spontaneous Ca2+ releases from the sarcoplasmic reticulum (SR) occurred in the diastolic interval between twitches (2.9 +/- 1.4 spontaneous SR Ca2+ oscillations/min; n = 7); alpha-adrenergic stimulation abolished these oscillations in six of seven cells. Thus, an increase in the frequency of spontaneous diastolic SR Ca2+ release (i.e., Ca2+ overload) is not the mechanism for the negative inotropic effect of alpha-adrenergic stimulation in 5 mM Ca0. In experiments with unstimulated myocytes, we determined whether the effect of alpha-adrenergic stimulation on cell Ca2+ homeostasis and oscillatory SR Ca2+ release observed in 5 mM Ca0 occurs only during electrical stimulation, when voltage-dependent currents are operative, or also at rest. Unstimulated rat ventricular myocytes in 5 mM Cao exhibit oscillatory SR Ca2+ release; alpha-adrenergic stimulation decreased the frequency of these oscillations to 53.9 +/- 8.9% of control, and this effect was blocked by 1 microM prazosin. In unstimulated indo-1-loaded myocytes alpha-adrenergic stimulation decreased the resting indo-1 fluorescence ratio in 5 mM Ca0, whereas it had no effect in 1 mM Ca0. Additional experiments were aimed at defining a role for Ca(2+)-activated, phospholipid-dependent protein kinase C (PKC) for the negative inotropic effect of alpha-adrenergic stimulation in 5 mM Ca0. Short-term preexposure to 0.1 microM 4 beta-phrobol 12-myristate 13-acetate (PMA) has been shown to maximally activate PKC.(ABSTRACT TRUNCATED AT 400 WORDS)
Salt-Sensitive Hypertension in Transgenic Mice Overexpressing Na <sup>+</sup> -Proton Exchanger
Authors: Makoto Kuro-o, Kazunori Hanaoka, Yukio Hiroi, Tsuyoshi Noguchi, Yumi Fujimori, Shun-ichi Takewaki, Michiko Hayasaka, Hirohisa Katoh, Akira Miyagishi, Ryozo Nagai, Yoshio Yazaki, Yo-ichi Nabeshima
Journal: Circulation Research (1995)

Abstract Essential hypertension is one of the most common diseases that exacerbate the risk of cardiovascular or cerebrovascular attacks. Although the etiology of essential hypertension remains unclear, recent investigations have revealed that an enhancement of Na + -proton (Na + -H + ) exchange activity is a frequently observed ion transport abnormality in hypertensive patients and animal models. To test the hypothesis that increased Na + -H + exchange causes hypertension, we produced transgenic mice overexpressing Na + -H + exchanger and analyzed their Na + metabolism and blood pressure. Urinary excretion of water and Na + was significantly decreased in transgenic mice, and systolic blood pressure was elevated after salt loading. The impaired urinary excretion of Na + suggested that the Na + -H + exchanger overexpressed in the renal tubules increased reabsorption of Na + , which caused a blood pressure elevation by Na + retention after excessive salt intake. Our results demonstrate that overexpression of Na + -H + exchanger can be a genetic factor that interacts with excessive salt intake and causes salt-sensitive blood pressure elevation.
Comparison of specialty referral rates in the United Kingdom and the United States: retrospective cohort analysis
Authors: C. B Forrest
Journal: BMJ (2002)

employing them.It is also important to invest sufficient resources to ensure that active interventions can be used to engage clinicians and to ensure that they find the time that is needed to change their routines.We thank Arild Bjørndal, Cheryl Carling, Jan Arve Dyrnes, Tor Arne Bertheussen, and Atle Fretheim for their help and support, the advisory committee for the project and the reference group
Gender difference in disease expression, radiographic damage and disability among patients with psoriatic arthritis
Authors: Lihi Eder, Arane Thavaneswaran, Vinod Chandran, Dafna D Gladman
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> The authors aimed to assess gender-related differences in severity of psoriatic arthritis (PsA) as reflected by measures of disease activity, joint damage, quality of life and disability. <h3>Methods</h3> A cross-sectional analysis was performed among patients who have been followed in a large PsA clinic. Demographic, clinical and radiographic data as well as information about quality of life and function were retrieved from the clinic database. Radiographic damage was assessed according to modified Steinbrocker score (mSS). The association between gender and the following outcome variables, radiographic joint damage, axial involvement and measures of quality of life and function, was assessed by multivariate regression analysis after adjustment for potential confounders. <h3>Results</h3> Three hundred and forty-five men and 245 women were included in the study. Axial involvement was more frequent in men (42.9% vs 31%, p=0.003). In multivariate analysis, adjusting for potential confounders, men were more likely to develop axial involvement (OR 1.8, p=0.003). Men were also more likely to develop more severe radiographic damage in the peripheral joints as evident by mSS. Men were more likely to be in a higher mSS damage category compared with women after adjusting for potential confounders in multivariate analysis (OR 1.6, p=0.007). Women suffered from more severe limitations in function and worse quality of life compared with men based on several patients9 reported outcomes. <h3>Conclusions</h3> Men with PsA are more likely to develop axial involvement and radiographic joint damage, while women are more likely to report about limitation in function and impaired quality of life.
Clinical Experience With Hedgehog Pathway Inhibitors
Authors: Jennifer A. Low, Frederic J. de Sauvage
Journal: Journal of Clinical Oncology (2010)

The Hedgehog (Hh) signaling pathway is critical for cell growth and differentiation during embryogenesis and early development. While it is mostly quiescent in adults, inappropriate reactivation of the Hh pathway has been shown to be involved in the development of cancer. A number of tumor types rely on overexpression of Hh ligands to activate the pathway in a paracrine manner from the tumor to the surrounding stroma. Alternatively, Hh ligands may act on cancer stem cells in some hematopoietic cancers, such as chronic myelogenous leukemia. However, the role of the Hh pathway is best established in tumors, such as basal cell carcinoma and medulloblastoma, where the pathway is activated via mutations. Understanding the contribution of Hh signaling in these various tumor types will be critical to the development and use of agents targeting this pathway in the clinic. We review here the activity of clinical inhibitors of the Hh pathway, including GDC-0449, a small molecule inhibitor of Smoothened (SMO).
Effect of sildenafil on acrolein-induced airway inflammation and mucus production in rats
Authors: T. Wang, Y. Liu, L. Chen, X. Wang, X-R. Hu, Y-L. Feng, D-S. Liu, D. Xu, Y-P. Duan, J. Lin, X-M. Ou, F-Q. Wen
Journal: European Respiratory Journal (2009)

Airway inflammation with mucus overproduction is a distinguishing pathophysiological feature of many chronic respiratory diseases. Phosphodiesterase (PDE) inhibitors have shown anti-inflammatory properties. In the present study, the effect of sildenafil, a potent inhibitor of PDE5 that selectively degrades cyclic guanosine 3′,5′-monophosphate (cGMP), on acrolein-induced inflammation and mucus production in rat airways was examined. Rats were exposed to acrolein for 14 and 28 days. Sildenafil or distilled saline was administered intragastrically prior to acrolein exposure. Bronchoalveolar lavage fluid (BALF) was acquired for cell count and the detection of pro-inflammatory cytokine levels. Lung tissue was examined for cGMP content, nitric oxide (NO)-metabolite levels, histopathological lesion scores, goblet cell metaplasia and mucin production. The results suggested that sildenafil pretreatment reversed the significant decline of cGMP content in rat lungs induced by acrolein exposure, and suppressed the increase of lung NO metabolites, the BALF leukocyte influx and pro-inflammatory cytokine release. Moreover, sildenafil pretreatment reduced acrolein-induced Muc5ac mucin synthesis at both mRNA and protein levels, and attenuated airway inflammation, as well as epithelial hyperplasia and metaplasia. In conclusion, sildenafil could attenuate airway inflammation and mucus production in the rat model, possibly through the nitric oxide/cyclic guanosine 3′,5′-monophosphate pathway, and, thus, might have a therapeutic potential for chronic airway diseases.
The double macchiato years; awards for the best basic science and epidemiology papers in 2012
Authors: Paul Cullinan, Clare Lloyd
Journal: Thorax (2013)

It9s increasingly difficult to get published in <i>Thorax</i> so we commend all those who managed it in 2012; and salute all those who tried and failed. We think that comparisons are invidious but our chief editors, with all their schoolboy charm, disagree so here are our awards for the best basic science and epidemiological manuscripts in the year of the London Olympics.
Clinical Scoring System to Predict Hepatocellular Carcinoma in Chronic Hepatitis B Carriers
Authors: Vincent Wai-Sun Wong, Stephen Lam Chan, Frankie Mo, Tung-Ching Chan, Herbert Ho-Fung Loong, Grace Lai-Hung Wong, Yanni Yan-Ni Lui, Anthony Tak-Cheung Chan, Joseph Jao-Yiu Sung, Winnie Yeo, Henry Lik-Yuen Chan, Tony Shu-Kam Mok
Journal: Journal of Clinical Oncology (2010)

Hepatitis B virus (HBV) infection is an important etiology for hepatocellular carcinoma (HCC). We aim to develop a simple clinical score in predicting the risk of HCC among HBV carriers.We first evaluated 1,005 patients and found that the following five factors independently predicted HCC development: age, albumin, bilirubin, HBV DNA, and cirrhosis. These variables were used to construct a prediction score ranging from 0 to 44.5. The score was validated in another prospective cohort of 424 patients.During a median follow-up of 10 years, 105 patients (10.%) in the training cohort and 45 patients (10.6%) in the validation cohort developed HCC. Cutoff values of 5 and 20 best discriminated HCC risk. By applying the cutoff value of 5, the score excluded future HCC development with high accuracy (negative predictive value = 97.8% and 97.3% in the training and validation cohorts, respectively). In the validation cohort, the 5-year HCC-free survival rates were 98.3%, 90.5%, and 78.9% in the low-, medium-, and high-risk groups, respectively. The hazard ratios for HCC in the medium- and high-risk groups were 12.8 and 14.6, respectively.A simple prediction score constructed from routine clinical and laboratory parameters is accurate in predicting HCC development in HBV carriers. Future prospective validation is warranted.