tbuckley/cabot-search huggingface dataset:
Cholesterol on the Web
Authors: Joan Stephenson
Journal: JAMA (1998)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Disseminated dermal melanocytosis terminating in melanoma.
Authors: ARNOLD LEVENE
Journal: British Journal of Dermatology (1979)

A detailed account is given of a progressive, punctate dermal melanocytosis which, commencing in childhood, terminated in the fifth decade as disseminated melanoma with no primary site discoverable. The terminal findings were characterized by prominent melanophagia. In the author's opinion there are resemblances between the unique condition described and a form of equine melanotic disease.
For and against: Cannabis control: costs outweigh the benefits * For * Against
Authors: A. Wodak, C. Reinarman, P. D A Cohen, C. Drummond
Journal: BMJ (2002)

ing enzyme inhibitors, blockers, and statins, and creates a potentially false gold standard for good medical care.The reader should not accept the conclusions of the Antithrombotic Trialists' Collaboration uncritically but rather read the original papers on which their conclusions are based.Competing interests: JC is a member of the steering committee for the WATCH (warfarin antiplatelet therapy in chronic heart failure) trial that compares the effects of warfarin, aspirin, and clopidogrel on outcome of 4500 patients with heart failure.This trial is being conducted by the US Veterans Administration and is partly financed by Sanofi.1 Antithrombotic Trialists' Collaboration.Prevention of death, myocardial infarction and stroke by antiplatelet therapy in high-risk patients.
PRISMS: A systematic meta-review of the evidence on supporting asthma self-management
Authors: Hilary Pinnock, Hannah Parke, Eleni Epiphaniou, Gemma Pearce, Steph Taylor
Journal: European Respiratory Journal (2014)

Aim:  To inform practical implementation of asthma self-management, we synthesised the findings of systematic reviews to provide a high-level overview.   Methods:  We systematically searched 7 electronic databases plus snowball and manual searches. Outcomes of interest: measures of asthma control, asthma-related quality of life. We investigated the composition, delivery, and setting of interventions in order to identify the optimal configuration of self-management support.   Results:  We included 18 systematic reviews (published 1995 – 2012) incorporating 157 randomised controlled trials. There is strong evidence that optimal self-management support (including a written action plan) reduces admissions and emergency department visits and increases quality of life in people with asthma. Interventions were diverse targeting healthcare professionals, patients and/or caregivers. Effective interventions were often tailored to specific populations (e.g. age, ethnicity, severity of disease) or to the context (e.g. in healthcare, school, or home settings) or mode of delivery (e.g. group, individual, telephone, computer)   Conclusion:  When developing self-management support services, it is essential to consider not only the content of the intervention, but also tailor the delivery mode and setting for the population and the healthcare context.   Funding:  NIHR HS&DR programme (project number 11/1014/04).  The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the HS&DR programme, NIHR, NHS or the Department of Health.
Effect of TGF-beta on functional properties of un-stretched and stretched neonatal lung (myo)fibroblast
Authors: Prajakta Oak, Nupoor Jain, Markus Koschlig, Tobias Reicherzer, Harald Ehrhardt, Anne Hilgendorff
Journal: European Respiratory Journal (2014)

Introduction Mechanical ventilation of an immature lung often leads to bronchopulmonary dysplasia (BPD) in preterm infants characterized by impaired alveolarization and vascularization, underlined by altered growth factor signaling. As the interplay of different factors triggering the disease remains unknown, we investigated the effect of stretch and TGF-β on functional and signaling properties of PDGF-R-α expressing mouse and human (myo)fibroblast (MFB).

Methods Primary MFBs isolated from lungs of P5-P7 C57BL/6 mice or from tracheal aspirates of preterm infants ≤29 weeks gestational age were either exposed to in vitro stretch (elongation max 10%; 30 cyc/min) or 5ng/ml TGF-β for 24h or both. Additionally, TGF-β was added to prestretched MFBs. Functional analyses included proliferation and migration. Growth factor signaling was assessed by immunoblot.

Results TGF-β reduced migration and increased proliferation in prestretched mouse MFBs, whereas stretch alone had no significant effect. In line with reduced migratory capacity, TGF-β treatment diminished PDGF-Rα expression and signaling in stretched as well as un-stretched MFBs. In human MFBs, a reduction in migration could be confirmed in stretched and prestretched MFBs upon TGF-β treatment depending on the disease grade. It was associated with diminished expression and signaling of PDGF-Rα in unstretched and stretched human MFBs.

Conclusion TGF-β exhibits stretch-dependant and –independent effects on mouse MFBs, that could be reproduced in primary human lung MFBs depending on disease grade. These findings indicate critical mechanisms in the time course of BPD pathophysiology with potential implications for treatment strategies.
When to perform hepatic resection for intermediate‐stage hepatocellular carcinoma
Authors: Alessandro Cucchetti, Benjamin Djulbegovic, Athanasios Tsalatsanis, Alessandro Vitale, Iztok Hozo, Fabio Piscaglia, Matteo Cescon, Giorgio Ercolani, Francesco Tuci, Umberto Cillo, Antonio Daniele Pinna
Journal: Hepatology (2014)

Transcatheter arterial chemoembolization (TACE) is the first‐line therapy recommended for patients with intermediate hepatocellular carcinoma (HCC). However, in clinical practice, these patients are often referred to surgical teams to be evaluated for hepatectomy. After making a treatment decision (e.g., TACE or surgery), physicians may discover that the alternative treatment would have been preferable, which may bring a sense of regret. Under this premise, it is postulated that the optimal decision will be the one associated with the least amount of regret. Regret‐based decision curve analysis (Regret‐DCA) was performed on a Cox's regression model developed on 247 patients with cirrhosis resected for intermediate HCC. Physician preferences on surgery versus TACE were elicited in terms of regret; threshold probabilities (P t ) were calculated to identify the probability of survival for which physicians are uncertain of whether or not to perform a surgery. A survey among surgeons and hepatologists regarding three hypothetical clinical cases of intermediate HCC was performed to assess treatment preference domains. The 3‐ and 5‐year overall survival rates after hepatectomy were 48.7% and 33.8%, respectively. Child‐Pugh score, tumor number, and esophageal varices were independent predictors of survival ( P &lt; 0.05). Regret‐DCA showed that for physicians with P t values of 3‐year survival between 35% and 70%, the optimal strategy is to rely on the prediction model; for physicians with Pt &lt;35%, surgery should be offered to all patients; and for P t values &gt;70%, the least regretful strategy is to perform TACE on all patients. The survey showed a significant separation among physicians' preferences, indicating that surgeons and hepatologists can uniformly act according to the regret threshold model. Conclusion : Regret theory provides a new perspective for treatment‐related decisions applicable to the setting of intermediate HCC. (H epatology 2015;61:905–914)
Abstract 15458: Prevalence and Burden of Abdominal Aortic Plaque Are Inversely Associated With Kidney Function: the Framingham Heart Study
Authors: Michael L Chuang, Philimon Gona, Noriko Oyama-Manabe, Daniel A Roseman, Gearóid M McMahon, Carol J Salton, Christopher J O’Donnell, Caroline S Fox, Warren J Manning
Journal: Circulation (2014)

Background: We sought to determine whether renal function as assessed by estimated glomerular filtration rate (eGFR) is independently associated with atherosclerotic abdominal aortic plaque (AAP). Methods: 1726 adults (65±9y, 53% women) from the Framingham Offspring cohort underwent cardiovascular magnetic resonance (CMR) abdominal imaging (axial T2W black-blood); prevalence and volume of AAP were quantified. Serum creatinine was measured at the adjacent cycle visit and eGFR was calculated using Chronic Kidney Disease Epidemiology Collaboration equations. We determined prevalence and volume of AAP by sex-specific quartiles of eGFR and tested for trend (Cochrane-Armitage) across quartiles. Multivariable-adjusted logistic regression models were used to determine odds of AAP per 10 units of eGFR. Results: For the entire group, eGFR was 84±18 ml/min/1.73m2 and did not differ between sexes. AAP prevalence decreased with increasing eGFR quartile in both sexes (Figure, top): p for trend &lt;0.0001 in men, p=0.0006 in women. Considering only study participants with AAP&gt;0, mean volume of AAP decreased (Figure, bottom) with greater eGFR quartile in both sexes, p&lt;0.0001 for men, p=0.004 for women. Trends remained significant when all study participants (including those with AAP=0) were analyzed. On logistic regression analyses every 10 units of eGFR decreased odds for prevalent AAP by 0.90 (95% confidence intervals 0.84 - 0.97) after adjustment for age, sex and traditional cardiovascular disease (CVD) risk factors; in the same model greater age (OR=1.28 per 10y; 1.10 - 1.48), smoking (OR=1.80; 1.24 - 2.62), and cholesterol treatment (OR=1.50; 1.12 - 2.02) were also associated with greater prevalence of AAP. Conclusion: Prevalence and burden of AAP both increase with decreasing eGFR in a community dwelling cohort of adults. Greater eGFR is independently associated with decreased prevalence of CMR-detected AAP even after adjustment for traditional CVD risk factors.
Abstract 1466: Regulation of colon cancer metastasis by sprouty-2
Authors: Qiong Zhang, Vivek Vaish, Sharad Khare
Journal: Cancer Research (2014)

Abstract Introduction: We earlier established that sprouty-2 is overexpressed in human colon cancer and up-regulates c-met and thereby increases the growth phenotype and metastatic potential of colon cancer cells (Oncogene, 29: 5241-53, 2010). To our knowledge, this was the first study to demonstrate the tumor oncogene phenotype of sprouty-2 in colon cancer metastasis. On the contrary, cancer protective role of sprouty-2 was noted in breast, liver and prostate cancers. However, a recent report on non-small cell lung cancer (NSCLC) discovered that silencing of sprouty-2 reduced c-met expression and thus confirmed our findings in colorectal cancer (PNAS, 110: 8573-78, 2013). We further extended our studies to demonstrate that this pathway modulates gastrointestinal specific microRNAs (miRNAs) and regulates various oncogenes and tumor suppressor genes in colon cancer cells. Methods: RNA from control and shRNA sprouty-2 transfected cells were labeled with Hy5 and Hy3 respectively and hybridized to miRCURY LNA arrays. Unsupervised miRNA clustering was carried out and a heat map prepared with Java TreeView. MicroRNA targets were identified by Real-time PCR, western blotting and 3′UTR luciferase assays. Migratory phenotype of colon cancer cells was confirmed by cell migration and invasion assays in trans-well chambers. Cancer cells were transfected by miRNA mimics to assess the expression levels of target genes. Human colon cancer tissue microarrays were utilized to assess the expression of miRNA target genes. Human tumor sections were evaluated by immunofluorescence and immunohistochemical staining. Results: Sprouty-2 shRNA transfected stable cell lines demonstrated upregulation of tumor suppressive miRNAs and down-regulation of oncogenic miRNAs. Overexpression of gastrointestinal specific miRNA mimics inhibits colon cancer cells proliferation and metastasis. On the contrary, overexpression of miRNA inhibitor in colon cancer cells promotes proliferation and colonization. Studies further indicated that miRNA down-regulates expression of CDK7, RB1, AKT, FASL, IGF1R, EGFR and N-cadherin and up-regulates expression of P21 and E-cadherin. MiRNA regulated genes were responsible for cell cycle arrest, enhanced apoptosis and decreased metastasis. AKT was upregulated whereas E-cadherin was downregulated at the invasive fronts in human colon tumors. Conclusion: Sprouty-2/miRNA expression levels could be used to risk-stratify patients for CRC recurrence and sprouty-2 axis regulation may lead to the development of therapeutics in colon and lung cancer. Citation Format: Qiong Zhang, Vivek Vaish, Sharad Khare. Regulation of colon cancer metastasis by sprouty-2. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1466. doi:10.1158/1538-7445.AM2014-1466
Association between attendance of day care centres and increased prevalence of eczema in the German birth cohort study LISAplus
Authors: C. Cramer, E. Link, C.-P. Bauer, U. Hoffmann, A. Von Berg, I. Lehmann, O. Herbarth, M. Borte, B. Schaaf, S. Sausenthaler, H.-E. Wichmann, J. Heinrich, U. Krämer
Journal: Allergy (2010)

Day care centre attendance is much more common in East than in West Germany. Although there is evidence that early day care might be protective against atopic diseases, several studies have shown a higher prevalence of childhood eczema in East Germany compared to West Germany.To compare prevalence and cumulative incidence of eczema in a birth cohort study in East and West Germany and to identify risk factors that are associated with eczema, which might explain regional differences.We used data from the ongoing population-based birth cohort study Influence of Life-style factors on the development of the Immune System and Allergies in East and West Germany Plus the influence of traffic emissions and genetics. In 1997, 3097 children from study areas in East and West Germany were recruited. Cumulative incidence and 1-year prevalences of eczema up to the age of 6 years were determined from yearly questionnaires. Cox regression and generalized estimating equations/logistic regression were used to quantify regional differences and to identify risk factors that might explain them.Prevalence and incidence of eczema were higher in children living in East Germany than those living in West Germany. We identified 11 risk factors that showed significant regional differences. From these factors, only 'day care attendance during the first 2 years of life' was significantly associated with eczema (odds ratio 1.56, 95% confidence interval CI 1.31-1.86). The regional differences in eczema could be explained by differences in early day care utilization.Day care centre attendance is associated with an increased prevalence and incidence of eczema. Regional differences in eczema prevalence could be explained by regional differences in utilization of early day care.
Abstract IA9: Vitamin D: Shining light on pancreatic cancer
Authors: Mara H. Sherman, Ning Ding, Eric A. Collisson, Michael Downes, Ronald M. Evans
Journal: Cancer Research (2015)

Abstract Pancreatic ductal adenocarcinoma (PDAC) occurs in the context of an exuberant desmoplastic response that produces a ‘living chimera’ of tumor and activated stromal components. A prominent feature of the stromal response is the transformation of the Vitamin A storing pancreatic stellate cell (PSC) to activated myofibroblasts. We hypothesized that restoration of the quiescent PSC phenotype could disrupt tumor-stroma crosstalk and thus improve response to chemotherapy. Recently, we have shown that the vitamin D receptor (VDR) is expressed at high levels in activated human pancreatic tumor stroma and, in response to ligand, acts as a master transcriptional regulator of PSCs to reprise the quiescent state. In vivo, a synthetic VDR agonist (Cal) induced signal-dependent transcriptional remodeling of tumor stroma, enhancing the anti-tumor effects of gemcitabine by increasing intratumoral concentration to reduce tumor growth. Secreted factors are key drivers of the communication between tumor and stroma. To explore the impact of PSC secreted factors on gene expression in pancreatic cancer, PDAC cell lines were grown in the presence of stromal conditioned media (StCM). Addition of StCM was sufficient to induce expression of thousands of PDAC genes linked to epigenetic reprograming including genome wide histone hyperacetylation. The gene expression profile induced by stromal factors overlap with those previously identified following oncogenic Kras, suggesting functional complementarity between cell-autonomous and micro-environmental cues. As epigenome modification results in changes in gene expression through histone modifications, we tested a small molecule inhibitors epigenetic regulators for the capacity to inhibit gene expression changes downstream of stromal factors. Paracrine induction of pro-growth and inflammatory genes was inhibited by this small molecule, suggesting that acetyl-lysine readers serve as key transducers of stromal inputs to drive alterations in gene expression in pancreatic cancer cells. This work describes a molecular strategy through which transcriptional reprogramming of tumors and tumor stroma by Vitamin D or epigenetic regulators may serve as a therapeutic portal in the treatment of pancreatic cancer. Citation Format: Mara H. Sherman, Ning Ding, Eric A. Collisson, Michael Downes, Ronald M. Evans. Vitamin D: Shining light on pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr IA9.
Abstract P25: Hypothermia Treatment Inhibits Cardiomyocytes Calcium Overload and Mitochondria Transition Permeability after Hypoxia- Reoxygenation Injuries
Authors: Chien-Hua Huang, Chiung-Yuan Hsu, Min-Shan Tsai, Huei-Wen Chen, Hsiao-Ju Cheng, Ren-How Pen, Wen-Jone Chen
Journal: Circulation (2008)

Introduction: Hypothermia treatment can provide cardiac protection against ischemia reperfusion injuries, but underlying mechanisms remain unclear. Hypothesis: Hypothermia-related cardiomyocyte protection is through the mitochondrial dependent pathways. Methods : H9c2 rat cardiomyocytes were cultured in 37°C, 5% CO 2 incubators. After initiation of hypoxia-reoxygenation (H-R) treatment, the H9c2 cells were moved to hypothermia (31°C) or kept in normothermia (37°C) environments until cells harvested. Cell damage, intracellular and mitochondria calcium loads were studies. Mitochondria permeability transition and transmembrane potentials were studies by flowcytometric studies. Results: Hypothermia treatment ameliorates H9c2 cardiomyocytes survival after H-R injuries (68.1±11.8% vs. 85.0±12.7 %, P=0.025). Intracellular and mitochondria calcium overloading after H-R injuries was improved under 31°C environment (153.5±16.4 % vs. 957.1±311.7 %, P&lt;0.01 for intracellular calcium; 101.8±28.5% vs. 159.4±32.5%, P=0.014 for mitochondria calcium). Mitochondria reductase activity were more preserved under hypothermia treatment after H-R injuries (55.7±10.9% vs. 8.5±1.2%, P&lt;0.01). Hypothermia treatment decreased the continuous opening of mitochondria permeability transition pore after H-R damage by less reduction of mitochondria calcein fluorescence (15.6±13.7 % vs. 52.8±28.1 %, P=0.003). Release of cytochrome c into the cytoplasm from mitochondria after H-R injuries was more evident in normothermia condition by confocal microscopy study. Activation of caspase-9, which is down-streaming to cytochrome c, was down-regulated under hypothermia (62.1±21.9% vs. 87.5±7.3%, P=0.019). Loss of mitochondria integrity with decreasing of mitochondria transmembrane potential was less evident in 31°C than 37°C environments (55.9±23.3% vs. 102±20.2%, P=0.016). Conclusion: Hypothermia treatment at 31°C provides cardiomyocyte protection against hypoxia-reoxygenation injuries. The mechanisms are related to the decreasing intracellular and mitochondria calcium overloading, preserving the integrity of mitochondria by reduction of mitochondria permeability transition pore opening and cytochrome c release.
Abstract 12934: Stent Design Affects the Side Branch Orifice Area Following Coronary Bifurcation Stenting: Comparison Between Resolute Integrity versus Xience V Stent Using a Newly Developed OCT algorithm
Authors: Yoshiyasu Minami, Zhao Wang, Stephen Lee, Shiro Uemura, Tsunenari Soeda, Owen Christopher Raffel, Peter Barlis, Tomonori Itoh, James Fujimoto, Ik-Kyung Jang
Journal: Circulation (2014)

Introduction: Bifurcation lesions remain a challenge in interventional cardiology. Preservation of side branch (SB) orifice may be affected by plaque distribution, SB orifice geometry, and stent design. We compared the open areas of a SB for the two widely used drug-eluting stents, Resolute Integrity (ZES) and Xience V (EES), using a newly developed OCT algorithm. Methods: From our registry database, we identified 123 consecutive cases with bifurcation (SB diameter ≥2.0mm) treated with ZES or EES. Among them, 88 de novo cases (ZES n=46, EES n=42) treated with a single stent were included in the final analysis. In collaboration with MIT, a new algorithm was developed to reconstruct the en face view from raw OCT data to evaluate the SB orifice accurately. Using this new algorithm the SB orifice area (A) and the area obstructed by struts (B) were calculated. The study endpoint was the percent open area defined as (A-B) / A*100. Results: Of 88 cases, 31 (14 ZES and 17 EES) cases were treated with SB dilatation and 57 (32 ZES and 25 EES) cases were treated with crossover stenting without SB dilatation. In those cases with SB dilatation, the %open area was not significantly different between ZES and EES (median, 91.4% vs 89.0%, P=0.33). However, the %open area was significantly smaller in ZES than in EES (median, 84.3% vs 89.2%, P=0.04) in crossover stenting. Multivariate analysis showed that the use of ZES was an independent predictor for the smaller %open area (below median, odds ratio 4.38, P=0.03) in crossover stenting. Conclusions: Using this newly developed algorithm to reconstruct OCT image en face, we demonstrated that the %open area was significantly smaller in Resolute Integrity than that in Xience V in crossover stenting, whereas no significant difference was seen between the two stents after SB dilatation. This finding indicates that stent design affects the SB open area and post dilatation may be important after Resolute Integrity stent implantation.