tbuckley/cabot-search huggingface dataset:
Perspectives in medical education: signposts to the future in educating respiratory specialists
Authors: P. Palange, J. Busari, A. Hare, J.H. McKillop, J-L.C. Noël, M.J. Rosen, A.K. Simonds, R. Stevenson
Journal: European Respiratory Journal (2012)

“Prediction is very difficult, particularly about the future.” Niels Bohr (1885–1962).

We are living in an exciting period due to current innovations and developments in science. As we learn more about the human gene, we try to cluster disorders and diseases in order to have a positive effect on medicine [1]. The Institute for Systems Biology (Seattle, WAS, USA) have developed the P4 medicine (or Predictive, Preventive, Personalised and Participatory medicine), in a move from traditional reactive medicine to proactive medicine. In the future, will the doctor actively search for the patient to predict and prevent a disease rather than wait? Will personalised and participatory care be given to all patients? [2]. There is no doubt that public health demand and research advances are pushing medicine into an era of transformation [3].

Fast moving societal, economical and technological changes are also reshaping the medical profession in general. The mobility of both patients and doctors within the European Union has focused even greater attention on the competency of doctors and their ability to practice medicine. Technological changes have introduced new concepts and challenges in how medical education is conducted, both by instruction and assessment.

In this milieu of complex and ever-evolving healthcare systems, how does the physician develop? How does one set expectations, provide experiences and evaluate outcomes which are the basic actions for providing a comprehensive programme in developing the physician as a professional? [4].

These trends will particularly impact on the practice of respiratory medicine. Therefore, it is crucial that the profession keeps pace. This requires particular efforts on behalf of the medical education reforms that have become relevant. The European Respiratory Society (ERS) took the first step in taking on the challenge. The ERS School organised an educational research seminar …
Cardiovascular Disease as a Long-Term Complication of Treatment for Testicular Cancer
Authors: R.A. Huddart, A. Norman, M. Shahidi, A. Horwich, D. Coward, J. Nicholls, D.P. Dearnaley
Journal: Journal of Clinical Oncology (2003)

Purpose: To assess the risk of cardiovascular morbidity and cardiac risk factors in long-term survivors of testicular cancer according to treatment received. Patients and Methods: All resident male patients registered in the United Kingdom between 1982 and 1992 attending for follow-up were eligible for recruitment. Patients completed a current health questionnaire and underwent clinical review, along with hematologic, biochemical, and hormonal profiles. For patients not under routine review, follow-up information was sought from their general practitioner and mortality data were sought from the Office of National Statistics. Descriptive analysis was performed on all variables and comparisons were made among patients treated by orchidectomy and follow-up only, chemotherapy alone (C), radiotherapy alone (RT), and radiotherapy and chemotherapy (C/RT). Results: Data on cardiovascular events were available on 992 patients. After a median follow-up of 10.2 years, 68 events had been reported, including 18 deaths. After adjusting for age, increased risk for cardiac events was seen after C (relative risk [RR] = 2.59; 95% confidence interval [CI], 1.15 to 5.84; P = .022), RT (RR = 2.40; 95% CI, 1.04 to 5.45; P = .036), and C/RT (RR = 2.78; 95% CI, 1.09 to 7.07; P = .032). There were no significant differences in cardiac risk factors. On multivariate analysis, age, treatment group, free thyroxine, protein, and magnesium levels were associated with cardiovascular disease. Conclusion: In long-term survivors of testicular cancer, we observed a two-fold or greater risk of developing cardiovascular disease. This was not due to increases in cardiac risk factors, which suggests a direct or indirect treatment effect. These data support the continued research into the minimization of treatment in good-prognosis testicular cancer.
Induction of CD14 in Tubular Epithelial Cells During Kidney Disease
Authors: JEREMIAH MORRISSEY, GUANGJIE GUO, RUTH MCCRACKEN, TIMOTHY TOLLEY, SAULO KLAHR
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Analysis of gene expression in a mouse model of unilateral ureteral obstruction (UUO) revealed significant induction of CD14 mRNA in kidneys with obstructed ureters. Immunocytochemical analysis indicated that CD14 was upregulated in tubular epithelial cells and this upregulation was not attributable to infiltration of the kidneys by mononuclear cells. This induction of CD14 mRNA was found to occur in BALB/C, C57BL/6, C3H/HeN, and C3H/HeJ mice during UUO. Ischemia/reperfusion of kidneys also induced CD14 mRNA. Mice lacking either of the tumor necrosis factor-α receptor (TNFR) genes were also studied; the induction of CD14 was blunted in TNFR 1-knockout mice but not in TNFR2-knockout mice. Apoptosis of tubular cells in lipopolysaccharide-resistant CH3/HeJ mice was significantly ( P &lt; 0.05) less than that in lipopolysaccharide-responsive CH3/HeN mice during UUO. These results suggest that CD14 is acutely induced in tubular epithelial cells in two mouse models of renal injury. This induction is regulated by tumor necrosis factor-α, through TNFR1. CD14 may participate in the apoptosis of tubular epithelial cells on a more chronic basis by activating a pathway that is absent or deficient in C3H/HeJ mice.
Racial Differences in Chronic Immune Stimulatory Conditions and Risk of Non-Hodgkin's Lymphoma in Veterans From the United States
Authors: Jill Koshiol, Tram Kim Lam, Gloria Gridley, David Check, Linda Morris Brown, Ola Landgren
Journal: Journal of Clinical Oncology (2010)

To examine underlying etiologic factors that may explain the racial disparity in non-Hodgkin's lymphoma (NHL) incidence patterns.We assessed immune-related conditions and risk of developing NHL among more than 4 million hospitalized US veterans including 9,496 patients with NHL (7,999 white patients and 1,497 black patients) with up to 26 years of follow-up. We used time-dependent Poisson regression to estimate rate ratios (RRs) and 95% CIs for NHL risk among patients with a history of specific autoimmune diseases, infections, and allergies compared with patients without such history, adjusting for attained age, calendar year, race, number of hospital visits, and time between study entry and exit.Patients with infectious conditions had an increased risk of developing NHL (RR, 1.2; 95% CI, 1.1 to 1.2), particularly for gastrohepatic, genital, and systemic infectious conditions. Patients with autoimmune disease were generally more likely to develop NHL than patients without autoimmune disease, especially for conditions that typically present with detectable autoantibodies with systemic involvement (RR, 2.0; 95% CI, 1.8 to 2.2). Allergies were also associated with increased risk (RR, 1.4; 95% CI, 1.3 to 1.5). Although the risk of NHL was lower for blacks than whites (RR, 0.87; 95% CI, 0.82 to 0.92), blacks had a slightly higher risk of NHL associated with infections than whites (likelihood ratio test, P = .002) and a tendency toward higher risk associated with allergies (likelihood ratio test, P = .05). Risks associated with autoimmune conditions were similar by race (likelihood ratio test, P = .5).The observed difference in NHL risk by race supports a role for race-related differences in genes regulating immune/inflammatory response.
cGMP-Elevating Agents Suppress Proliferation of Vascular Smooth Muscle Cells by Inhibiting the Activation of Epidermal Growth Factor Signaling Pathway
Authors: Sheu-Meei Yu, Li-Man Hung, Chia-Chih Lin
Journal: Circulation (1997)

Background Abnormal proliferation of vascular smooth muscle cells (VSMC) is a key event in the pathogenesis of atherosclerosis and many vascular diseases. It is known that nitric oxide released from the endothelium participates in the regulation of VSMC proliferation via a cyclic 3′,5′-guanosine monophosphate (cGMP)-mediated mechanism. In a series of experiments, sodium nitroprusside (SNP) and A02131 -1 were evaluated for their antiproliferative effect and the mechanism of their cGMP-elevating action. Methods and Results The effect of SNP and A02131-1 on epidermal growth factor (EGF)-stimulated proliferation of rat aortic smooth muscle cells (VSMC) was examined. Cell proliferation was measured in terms of [ 3 H]thymidine incorporation, flow cytometry, and the cell number. Further, their effect on the EGF-activated signal transduction pathway was assessed by measuring mitogen-activated protein kinases (MAPK), MAPK kinase (MEK), Raf-1 activity, and the formation of active form of Ras . SNP and A02131-1 inhibited EGF-induced DNA synthesis and subsequent proliferation of VSMC. These two increased cGMP but only a little cAMP in VSMC. A similar antiproliferative effect was observed with 8-bromo-cGMP. The antiproliferative effect of the two was reversed by KT5823 but not by dideoxyadenosine nor Rp-cAMPS. SNP and A02131-1 blocked the EGF-inducible cell cycle progression at the G1/S phase. Further experiments indicated that the two cGMP-elevating agents primarily blocked the activation of Raf-1 by EGF-activated Ras . Conclusions These results demonstrate that cGMP-elevating agents inhibit [ 3 H]thymidine incorporation and thus the growth of VSMC, and this inhibition appears to attenuate EGF-activated signal transduction pathway by preventing Ras -dependent activation of Raf-1.
Patient-Specific Prediction of ESRD after Liver Transplantation
Authors: Pratima Sharma, Nathan P. Goodrich, Douglas E. Schaubel, Mary K. Guidinger, Robert M. Merion
Journal: Journal of the American Society of Nephrology (2013)

Incident ESRD after liver transplantation (LT) is associated with high post-transplant mortality. We constructed and validated a continuous renal risk index (RRI) to predict post-LT ESRD. Data for 43,514 adult recipients of deceased donor LT alone (February 28, 2002 to December 31, 2010) were linked from the Scientific Registry of Transplant Recipients and the Centers for Medicare and Medicaid Services ESRD Program. An adjusted Cox regression model of time to post-LT ESRD was fitted, and the resulting equation was used to calculate an RRI for each LT recipient. The RRI included 14 recipient factors: age, African-American race, hepatitis C, cholestatic disease, body mass index≥35, pre-LT diabetes, ln creatinine for recipients not on dialysis, ln albumin, ln bilirubin, serum sodium<134 mEq/L, status-1, previous LT, transjugular intrahepatic portosystemic shunt, and acute dialysis at LT. This RRI was validated and had a C statistic of 0.76 (95% confidence interval, 0.75 to 0.78). Higher RRI associated significantly with higher 5-year cumulative incidence of ESRD and post-transplant mortality. In conclusion, the RRI constructed in this study quantifies the risk of post-LT ESRD and is applicable to all LT alone recipients. This new validated measure may serve as an important prognostic tool in ameliorating post-LT ESRD risk and improve survival by informing post-LT patient management strategies.
Development of a novel peptide microarray for large-scale epitope mapping of food allergens
Authors: Jing Lin, Ludmilla Bardina, Wayne G. Shreffler, Doerthe A. Andreae, Yongchao Ge, Julie Wang, Francesca M. Bruni, Zhiyan Fu, Youngshin Han, Hugh A. Sampson
Journal: Journal of Allergy and Clinical Immunology (2009)
Hepcidin is localised in gastric parietal cells, regulates acid secretion and is induced by<i>Helicobacter pylori</i>infection
Authors: Peggy Schwarz, Johanna A M Kübler, Pavel Strnad, Katrin Müller, Thomas F E Barth, Andreas Gerloff, Peter Feick, Carole Peyssonnaux, Sophie Vaulont, Guido Adler, Hasan Kulaksiz
Journal: Gut (2011)

<h3>Backgrounds and aims</h3> Hepcidin is an antimicrobial peptide and the central regulator of iron metabolism. Given that hepcidin was shown to be expressed in a variety of extrahepatic tissues and that stomach plays a role in iron absorption and in defence against infections, this study analysed the importance of hepcidin in the stomach. <h3>Methods</h3> Expression and localisation of gastric hepcidin was studied by quantitative RT-PCR, western blot, immunofluorescence and in situ hybridisation. Regulation of gastric hepcidin expression was analysed both in vitro and in vivo. Hepcidin wild-type (WT) and knockout (KO) animals were used to determine the impact of hepcidin on gastric bacterial overgrowth as well as gastric acid secretion. <h3>Results</h3> Hepcidin was abundantly expressed in the gastric fundus and corpus of all tested species. Treatment of AGS cells with ferric nitrilotriacetate solution downregulated hepcidin expression levels, while desferroxamine, interleukin 6 and <i>Helicobacter pylori</i> infection upregulated it. In humans, gastric hepcidin expression was elevated during <i>H pylori</i> infection and normalised after successful eradication. Gastric hepcidin is localised in parietal cells that are indispensable for gastric acid secretion. Comparisons of WT and hepcidin KO mice revealed that acid secretion in hepcidin-deficient mice is markedly reduced and is associated with gastric bacterial overgrowth, expression changes in multiple factors involved in acid secretion (<i>Atp4a</i>, <i>Cck2r</i>,<i>Gas</i>, <i>Sst</i> and <i>Sst2r</i>) and with reduced circulating gastrin levels. In WT mice, pantoprazole activated and histamine downregulated hepcidin expression levels. <h3>Conclusions</h3> Hepcidin is a product of parietal cells regulating gastric acid production and may contribute to development of gastric ulcers under stress conditions.
Hepatic fibrogenesis requires sympathetic neurotransmitters
Authors: J A Oben
Journal: Gut (2004)

Hepatic stellate cells (HSC) are activated by liver injury to become proliferative fibrogenic myofibroblasts. This process may be regulated by the sympathetic nervous system (SNS) but the mechanisms involved are unclear.We studied cultured HSC and intact mice with liver injury to test the hypothesis that HSC respond to and produce SNS neurotransmitters to promote fibrogenesis.HSC expressed adrenoceptors, catecholamine biosynthetic enzymes, released norepinephrine (NE), and were growth inhibited by alpha- and beta-adrenoceptor antagonists. HSC from dopamine beta-hydroxylase deficient (Dbh(-/-)) mice, which cannot make NE, grew poorly in culture and were rescued by NE. Inhibitor studies demonstrated that this effect was mediated via G protein coupled adrenoceptors, mitogen activated kinases, and phosphatidylinositol 3-kinase. Injury related fibrogenic responses were inhibited in Dbh(-/-) mice, as evidenced by reduced hepatic accumulation of alpha-smooth muscle actin(+ve) HSC and decreased induction of transforming growth factor beta1 (TGF-beta1) and collagen. Treatment with isoprenaline rescued HSC activation. HSC were also reduced in leptin deficient ob/ob mice which have reduced NE levels and are resistant to hepatic fibrosis. Treating ob/ob mice with NE induced HSC proliferation, upregulated hepatic TGF-beta1 and collagen, and increased liver fibrosis.HSC are hepatic neuroglia that produce and respond to SNS neurotransmitters to promote hepatic fibrosis.
Management of lower gastrointestinal bleeding with haemodynamic instability
Authors: K-L Liu, C-W Lee, W-J Lee, Y-M Tsang, B-R Lin
Journal: Gut (2008)

A 76-year-old woman presented to our emergency department owing to torrential fresh rectal bleeding. Bloody stool had been noted for 3 days and was believed to be caused by haemorrhoids. There was no medical …
Molecular Evidence Supporting Field Effect in Urothelial Carcinogenesis
Authors: Timothy D. Jones, Mingsheng Wang, John N. Eble, Gregory T. MacLennan, Antonio Lopez-Beltran, Shaobo Zhang, Amy Cocco, Liang Cheng
Journal: Clinical Cancer Research (2005)

Human urothelial carcinoma is thought to arise from a field change that affects the entire urothelium. Multifocality of urothelial carcinoma is a common finding at endoscopy and surgery. Whether these coexisting tumors arise independently or are derived from the same tumor clone is uncertain. Molecular analysis of microsatellite alterations and X-chromosome inactivation status in the cells from each coexisting tumor may further our understanding of urothelial carcinogenesis.We examined 58 tumors from 21 patients who underwent surgical excision for urothelial carcinoma. All patients had multiple separate foci of urothelial carcinoma (two to four) within the urinary tract. Genomic DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-capture microdissection. Loss of heterozygosity (LOH) assays for three microsatellite polymorphic markers on chromosome 9p21 (IFNA and D9S171), regions of putative tumor suppressor gene p16, and on chromosome 17p13 (TP53), the p53 tumor suppressor gene locus, were done. X-chromosome inactivation analysis was done on the urothelial tumors from 11 female patients.Seventeen of 21 (81%) cases showed allelic loss in one or more of the urothelial tumors in at least one of the three polymorphic markers analyzed. Concordant allelic loss patterns between each coexisting urothelial tumor were seen in only 3 of 21 (14%) cases. A concordant pattern of nonrandom X-chromosome inactivation in the multiple coexisting urothelial tumors was seen in only 3 of 11 female patients; of these 3 cases, only one displayed an identical allelic loss pattern in all of the tumors on LOH analysis.LOH and X-chromosome inactivation assays show that the coexisting tumors in many cases of multifocal urothelial carcinoma have a unique clonal origin and arise from independently transformed progenitor urothelial cells, supporting the "field effect" theory for urothelial carcinogenesis.
The dynamics of development: Challenges for Bayesian rationality
Authors: Nils Straubinger, Edward T. Cokely, Jeffrey R. Stevens
Journal: Behavioral and Brain Sciences (2009)

Abstract Oaksford &amp; Chater (O&amp;C) focus on patterns of typical adult reasoning from a probabilistic perspective. We discuss implications of extending the probabilistic approach to lifespan development, considering the role of working memory, strategy use, and expertise. Explaining variations in human reasoning poses a challenge to Bayesian rational analysis, as it requires integrating knowledge about cognitive processes.
Relation between falciparum malaria and bacteraemia in Kenyan children: a population-based, case-control study and a longitudinal study
Authors: J Anthony G Scott, James A Berkley, Isaiah Mwangi, Lucy Ochola, Sophie Uyoga, Alexander Macharia, Carolyne Ndila, Brett S Lowe, Salim Mwarumba, Evasius Bauni, Kevin Marsh, Thomas N Williams
Journal: The Lancet (2011)
Loose Connections between Peer-Reviewed Clinical Journals and Clinical Practice
Authors: R B Haynes
Journal: Annals of Internal Medicine (1990)

Many important advances in medical care are first reported in the biomedical literature, but physicians find the literature overwhelming and, therefore, are often unaware of advances. This article examines the ways in which peer-reviewed clinical journals contribute to this problem and proposes some solutions for both their editors and clinical readers. Peer-reviewed clinical journals impede the dissemination of validated advances to practitioners by mixing a few rigorous studies (communications from scientists to practitioners) with many preliminary investigations (communications from scientists to scientists). Journals wishing to improve communication with practitioners should feature rigorous studies of the nature, cause, prognosis, diagnosis, prevention, and treatment of disease and should feature sound clinical review articles (communications from practitioners to practitioners). Additional strategies for improving communication between medical scientists and practitioners include improving publication standards for clinical journals, providing more informative abstracts for clinical articles, fostering the development of derivative literature services, and enhancing practitioners' skills in critically appraising the medical literature.
Lung Function, Bronchial Responsiveness, and Asthma in a Community Cohort of 6-Year-Old Children
Authors: Jacqui Joseph-Bowen, Nicholas H. de Klerk, Martin J. Firth, Garth E. Kendall, Patrick G. Holt, Peter D. Sly
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Children as young as 6 years old can perform spirometry, yet the relationship between current asthma, lung function, and bronchial responsiveness has not been described at this age; 2,537 children from a community-based birth cohort were assessed at 6 years of age, with history (n = 2,141), physical examination (n = 1,995), standard spirometry (n = 1,735), and a random sample (n = 711) offered methacholine challenge. Males had greater values of FVC and FEV(1) but not of mean forced expiratory flow during the middle half of the FVC or FEV(1)/FVC than females. The greatest influences on lung function at 6 years were height, sex, birth weight, and wheezing in the first year of life. Children with current asthma had small but significant deficits in lung function and were more sensitive to methacholine. The optimal cutpoint for determining heightened bronchial responsiveness was found to be a 15% fall in FEV(1) at a dose of 1.8 mg/ml. A negative test could be useful in excluding a diagnosis of asthma (negative predictive value of 92%). Lung function testing, including methacholine challenge, is feasible in 5- to 7-year-old children and has the potential to contribute to the clinical management of children with asthma.
The trendy microbes
Authors: VK Viswanathan
Journal: Gut Microbes (2014)

After dominating the earth in numbers and biomass for a good 3.5 billion years, microbes are now finally in the public consciousness. The vigorous surge in the study of microbes promises to yield novel approaches to treating diseases and maintaining health. In the middle of the deluge of scientific publications and lay articles, we pause to reflect on this trend.
A new NMR-based metabolomics approach for the diagnosis of biliary tract cancer
Authors: He Wen, Sung Soo Yoo, Jinho Kang, Hee Goo Kim, Jin-Seok Park, Seok Jeong, Jung Il Lee, Hyuk Nam Kwon, Sunmi Kang, Don-Haeng Lee, Sunghyouk Park
Journal: Journal of Hepatology (2009)
The Tricuspid Valve
Authors: Jason H. Rogers, Steven F. Bolling
Journal: Circulation (2009)

Cardiovascular specialists have entered an era of renewed interest and enthusiasm surrounding the diagnosis and treatment of valvular heart disease, driven in part by emerging percutaneous therapies for the treatment of aortic, pulmonic, and mitral valve disease. Despite this wave of investigation, little or no attention has been given to the treatment of tricuspid valve disease. Tricuspid regurgitation (TR) occurs mainly from tricuspid annular dilation, which can result from left-sided heart failure from myocardial or valvular causes, right ventricular volume and pressure overload, or dilation of cardiac chambers. If untreated at the time of surgical mitral valve repair, significant residual TR negatively impacts perioperative outcomes, functional class, and survival. TR does not reliably resolve after successful mitral valve surgery. If present at the time of mitral valve surgery, TR can usually be effectively addressed with ring annuloplasty. Because reoperations for recurrent TR carry high mortality rates, few patients are offered reoperation for redo tricuspid repair or replacement. As transcatheter therapies for mitral regurgitation arise, parallel percutaneous approaches for TR may be necessary. In this article, we review the anatomy, pathophysiology, and value of mechanical correction of TR, including potential transcatheter therapies for TR.