tbuckley/cabot-search huggingface dataset:
Plasma concentration of cross-linked fibrin degradation product (D-dimer) and the risk of future myocardial infarction among apparently healthy men.
Authors: P M Ridker, C H Hennekens, A Cerskus, M J Stampfer
Journal: Circulation (1994)

BACKGROUND Plasma levels of D-dimer, the primary degradation product of cross-linked fibrin, are elevated in several acute thrombotic disorders. However, whether elevated D-dimer levels among healthy individuals are associated with future coronary thrombosis is unknown. METHODS AND RESULTS To evaluate whether levels of D-dimer are associated with the occurrence of future myocardial infarction (MI) among apparently healthy men, levels were measured in plasma samples collected at baseline from 296 participants in the Physicians' Health Study who later developed a first MI and from an equal number of age- and smoking status-matched control subjects who remained free of vascular disease during a mean follow-up period of 60.2 months. In univariate analyses, baseline plasma concentrations of D-dimer in the upper ranges of normal were associated with elevated risks of MI. Specifically, the relative risk of future MI for individuals with baseline D-dimer concentration exceeding the 95th percentile of the control distribution was two times higher than that of individuals with lower levels (relative risk [RR], 2.02; 95% confidence interval [CI], 1.04 to 4.02; P = .04). This association persisted in multivariate analyses controlling for nonlipid cardiovascular risk factors (RR, 2.12; 95% CI, 1.05 to 4.28; P = .04) and for lipoprotein(a) (RR, 2.02; 95% CI, 1.04 to 3.94; P = .03). In contrast, this association was attenuated and no longer statistically significant in analyses that controlled for total and high-density lipoprotein cholesterol (RR, 1.74; 95% CI, 0.78 to 3.91; P = .2) or for endogenous tissue-type plasminogen activator and its primary inhibitor, plasminogen activator inhibitor type 1 (RR, 1.58; 95% CI, 0.67 to 3.77; P = .3). CONCLUSIONS Elevated levels of D-dimer are associated with increased risks of future MI, although they do not appear to be an independent predictor when other risk factors are considered. As the presence of D-dimer in plasma reflects ongoing fibrin degradation, these data support the hypothesis that activation of the endogenous fibrinolytic system occurs many years in advance of coronary arterial occlusion.
Socioeconomic and ethnic group differences in self reported health status and use of health services by children and young people in England: cross sectional study
Authors: S. Saxena
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objectives:</b> To examine whether self reported health status and use of health services varies in children of different social class and ethnic group. <b>Design:</b> Cross sectional study from the 1999 health survey for England. <b>Subjects:</b> 6648 children and young adults aged 2-20 years. <b>Setting:</b> Private households in England. <b>Main outcome measures:</b> Proportion of children (or their parents) reporting episodes of acute illness in the preceding fortnight and prevalence of self reported longstanding illness. Proportion reporting specific illnesses. Proportion reporting that they had consulted a general practitioner in the preceding fortnight, attended hospital outpatient departments in the three preceding months, or been admitted to hospital in the preceding year. <b>Results:</b> Large socioeconomic differences were observed between ethnic subgroups; a higher proportion of Afro-Caribbean, Indian, Pakistani, and Bangladeshi children belonged to lower social classes than the general population. The proportion of children and young adults reporting acute illnesses in the preceding two weeks was lower in Bangladeshi and Chinese subgroups (odds ratio 0.41, 95% confidence interval 0.27 to 0.61 and 0.46, 0.28 to 0.77, respectively) than in the general population. Longstanding illnesses was less common in Bangladeshi and Pakistani children (0.52, 0.40 to 0.67 and 0.57, 0.46 to 0.70) than in the general population. Irish and Afro-Caribbean children reported the highest prevalence of asthma (19.5% and 17.7%) and Bangladeshi children the lowest (8.2%). A higher proportion of Afro-Caribbean children reported major injuiries than the general population (11.0% <i>v</i> 10.0%), and children from all Asian subgroups reported fewer major and minor injuries than the general population. Indian and Pakistani children were more likely to have consulted their general practitioner in the preceding fortnight than the general population (1.86, 1.35 to 2.57 and 1.51, 1.13 to 2.01, respectively). Indian, Pakistani, Bangladeshi, and Chinese children were less likely to have attended outpatient departments in the preceding three months. No significant differences were found between ethnic groups in the admission of inpatients to hospitals. Acute and chronic illness were the best predictors of children9s use of health services. Social classes did not differ in self reported prevalence of treated infections, major injuries, or minor injuries, and no socioeconomic differences were seen in the use of primary and secondary healthcare services. <b>Conclusions:</b> Children9s use of health services reflected health status rather than ethnic group or socioeconomic status, implying that equity of access has been partly achieved, although reasons why children from ethnic minority groups are able to access primary care but receive less secondary care need to be investigated.
Is Co-option a Prevailing Mechanism during Cancer Progression?
Authors: Marc Billaud, Massimo Santoro
Journal: Cancer Research (2011)

Abstract Cancer progression results from the accumulation of genetic and epigenetic alterations that provide tumor cells with a selective advantage. The consecutive cycles of mutations, selections, and clonal expansions generate, over time, descendant cells with increasing malignant properties. Although this conception of tumor development rests on solid experimental foundations, it has also raised several persisting questions. Does the succession of mutations dictate the progression of each cancer type or does the disturbance of an invariant set of regulatory circuits govern tumor evolution regardless of the linear order of genetic events? Is the ability of malignant cells to disseminate and spawn metastasis a property acquired at late stages of tumor development or is the proclivity to metastasize implanted early during cancer formation? Considering these issues, we elaborate here on the concept of co-option that refers to the emergence of novel functions from ancestral characters during episodes of organismal evolution. As discussed in this Perspective, co-option seems to be a key mechanism propelling the molecular engine that drives malignant transformation. Hence, this notion may constitute a unifying principle that connects a large body of experimental results to clinical observations. Cancer Res; 71(21); 6572–5. ©2011 AACR.
Permselectivity in thin membrane nephropathy.
Authors: D M Thomas, G A Coles, D F Griffiths, J D Williams
Journal: Journal of Clinical Investigation (1994)

The glomerular permselectivity to polydisperse neutral dextrans was compared in 6 patients with thin membrane nephropathy (TMN) and 10 healthy controls. Despite having normal renal hemodynamics and minimal proteinuria, the patients with TMN had significantly increased fractional clearance of neutral molecules with Stokes radius > 42 A. Conventional theories of glomerular barrier size selectivity cannot fully explain these data since they would predict that our patients would have had nephrotic range proteinuria.
Aldosterone Regulates MicroRNAs in the Cortical Collecting Duct to Alter Sodium Transport
Authors: Robert S. Edinger, Claudia Coronnello, Andrew J. Bodnar, William A. LaFramboise, Panayiotis V. Benos, Jacqueline Ho, John P. Johnson, Michael B. Butterworth
Journal: Journal of the American Society of Nephrology (2014)

A role for microRNAs (miRs) in the physiologic regulation of sodium transport in the kidney has not been established. In this study, we investigated the potential of aldosterone to alter miR expression in mouse cortical collecting duct (mCCD) epithelial cells. Microarray studies demonstrated the regulation of miR expression by aldosterone in both cultured mCCD and isolated primary distal nephron principal cells. Aldosterone regulation of the most significantly downregulated miRs, mmu-miR-335–3p, mmu-miR-290–5p, and mmu-miR-1983 was confirmed by quantitative RT-PCR. Reducing the expression of these miRs separately or in combination increased epithelial sodium channel (ENaC)–mediated sodium transport in mCCD cells, without mineralocorticoid supplementation. Artificially increasing the expression of these miRs by transfection with plasmid precursors or miR mimic constructs blunted aldosterone stimulation of ENaC transport. Using a newly developed computational approach, termed ComiR, we predicted potential gene targets for the aldosterone-regulated miRs and confirmed ankyrin 3 (Ank3) as a novel aldosterone and miR-regulated protein. A dual-luciferase assay demonstrated direct binding of the miRs with the Ank3–3′ untranslated region. Overexpression of Ank3 increased and depletion of Ank3 decreased ENaC-mediated sodium transport in mCCD cells. These findings implicate miRs as intermediaries in aldosterone signaling in principal cells of the distal kidney nephron.
An Atlas of Diseases of the Nail
Authors: Celia Moss
Journal: Journal of the Royal Society of Medicine (2004)

Readers are attracted to books by their appearance as well as their subject, and this one looks tempting, with stylish layout, clear headings and a good balance of pictures and text. The introductory chapter on nail anatomy and basic science is straightforward, although the two references are at least 7 years old. An alphabetical catalogue of nail signs and their definitions is neat and concise until ‘O’, where it digresses into aetiology and management. A classification by colour is marred by linguistic indecision, with separate sections on ‘red nails’ and ‘erythronychia’. Chapters on infections, signs of cutaneous and systemic disease, and age-related disorders contain repetitions, inaccuracies and the sort of pictures most dermatologists keep in their collections. By the time we reach ‘nail surgery’ and ‘nail cosmetics’ the temptation has worn off.

It is unclear who this book is aimed at. Those keen to differentiate onychorrhexis, onychauxis and onychocryptosis (caused by ‘faulty biomechanics in the elderly’) would want more facts. It is impossible to look them up because the index, at least in my copy, stops abruptly and mysteriously at N (for nail). Those seeking treatment advice will find it unreferenced, incomplete and sometimes bizarre: examples include biotin for brittle nails, omission of amorolfine and tioconazole as topical antifungals, and digital amputation for keratoacanthoma. Illustrations of ‘epidermolysis bullosa simplex’ (which rarely affects the nails) clearly show the scarring, milia and nail dystrophy characteristic of dystrophic epidermolysis bullosa. I would like the lay public to learn that those ubiquitous little white dots and lines (‘punctate and transverse leuconychia’) are caused by minor trauma, not calcium deficiency, but despite its coffee-table format this is not a book to leave in your sitting room. Some gruesome pictures are rendered more lurid by unfortunate colour balancing, while others are mercifully overexposed.

To their credit, these authors clearly love their subject. They particularly like Beau's lines, which pop up with almost the same text in three different chapters. They enthuse over longitudinal ridges and bands. They enjoy nail pits. And they cannot resist the visual economy of photographing nails next to an associated anomaly. This is sometimes effective—for example, in showing the nail and mucosal pigmentation of Laugier-Hunziger syndrome. More often one or both abnormalities are out of focus, the patients apparently gesturing incomprehensibly. At least this atlas demonstrates a trick unknown to medical photographers, that fingernails are better photographed from the palmar aspect of the hand with fingers flexed and nails approximated, than from the dorsal aspect with fingers straight and nails far apart.
Direct-to-Consumer Marketing of Genetic Tests for Cancer: Buyer Beware
Authors: Stacy Gray, Olufunmilayo I. Olopade
Journal: Journal of Clinical Oncology (2003)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.12.069 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12874271 Direct-to-Consumer Marketing of Genetic Tests for Cancer: Buyer Beware Stacy GrayxStacy GraySearch for articles by this author , Olufunmilayo I. OlopadexOlufunmilayo I. OlopadeSearch for articles by this author Show More Center for Clinical Cancer Genetics, Department of Medicine, and University of Chicago Pritzker School of Medicine, Chicago, IL https://doi.org/10.1200/JCO.2003.12.069 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
A Mediator Role For Metallothionein in Tumor Necrosis Factor–induced Lethal Shock
Authors: Wim Waelput, Daniël Broekaert, Joël Vandekerckhove, Peter Brouckaert, Jan Tavernier, Claude Libert
Journal: The Journal of Experimental Medicine (2001)

Tumor necrosis factor (TNF) is a proinflammatory cytokine, which is centrally involved in several inflammatory disorders. Administration of TNF leads to a potentially lethal systemic inflammatory response syndrome (SIRS). We observed that (a) mice lacking functional genes for metallothionein 1 and 2 (MT-null) were protected compared with wild-type controls (P = 0.0078), and (b) mice overexpressing MT-1 (MT-TG) were more sensitized for the lethal effect of TNF than control mice (P = 0.0003), indicating a mediating role for MT in TNF induced SIRS. As MT is involved in the body zinc homeostasis, we tested whether zinc-deprivation or -supplementation alters the response to TNF. Although zinc-depletion strongly sensitized (P = 0.036), and pretreatment with zinc sulfate (ZnSO4) conferred protection against the deleterious effects of TNF (P &amp;lt; 0.0002), it was also found that the protection provided by zinc is independent of MT. Our observation that hsp70 is strongly induced in jejunum after ZnSO4 treatment, suggests a contribution of hsp70 in the protection against TNF. In addition, ZnSO4 cotreatment allowed complete regression of inoculated tumors with TNF and interferon γ, leading to a significantly better survival (P = 0.0045).
Pediatric Endocrinologists' Management of Children With Type 2 Diabetes
Authors: Kam Wong, Amy Potter, Shelagh Mulvaney, William E. Russell, David G. Schlundt, Russell L. Rothman
Journal: Diabetes Care (2009)

OBJECTIVE To understand physician behaviors and attitudes in managing children with type 2 diabetes. RESEARCH DESIGN AND METHODS A survey was mailed to a nationwide sample of pediatric endocrinologists (PEs). RESULTS A total of 40% of PEs surveyed responded (211 of 527). Concordance with current monitoring guidelines varied widely, ranging from 36% (foot care) to 93% (blood pressure monitoring). Given clinical vignettes addressing hyperlipidemia, hypertension, and microalbuminuria, only 34% of PEs were fully concordant with current treatment guidelines. Reported barriers included concerns about patient adherence, insufficient scientific evidence about treatment, and lack of familiarity with current recommendations. Providers aged ≤45 years or in clinical practice &amp;lt;10 years reported significantly more aggressive management behaviors and had higher concordance with guidelines. CONCLUSIONS Screening and management of pediatric type 2 diabetes varied widely among PEs, suggesting opportunities for quality improvement. More aggressive management of type 2 diabetes among younger providers may be related to recent training when type 2 diabetes was more common.
Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes
Authors: Jialing Huang, Fengxiang Wang, Elias Argyris, Keyang Chen, Zhihui Liang, Heng Tian, Wenlin Huang, Kathleen Squires, Gwen Verlinghieri, Hui Zhang
Journal: Nature Medicine (2007)
Detection of <i>KRAS</i> Oncogene in Peripheral Blood as a Predictor of the Response to Cetuximab Plus Chemotherapy in Patients with Metastatic Colorectal Cancer
Authors: Li-Chen Yen, Yung-Sung Yeh, Chao-Wen Chen, Hwei-Ming Wang, Hsiang-Lin Tsai, Chien-Yu Lu, Yu-Tang Chang, Koung-Shing Chu, Shiu-Ru Lin, Jaw-Yuan Wang
Journal: Clinical Cancer Research (2009)

Previously we developed membrane-arrays as a promising tool to detect circulating tumor cells (CTC) with KRAS oncogene in patients with malignancies. This study was conducted to determinate the predictive values of CTCs with KARS mutation by membrane-arrays for metastatic colorectal cancer patients treated with cetuximab plus chemotherapy.Seventy-six metastatic colorectal cancer patients receiving cetuximab plus FOLFIRI or FOLFOX-4 chemotherapy were enrolled. KRAS mutation status in the peripheral blood of these patients was analyzed using membrane-arrays, and KRAS mutation status in tumors was analyzed by DNA sequencing.Among 76 metastatic colorectal cancer patients, KRAS mutations in tumors and in peripheral blood were identified in 33 (43.4%) and 30 (39.5%) patients, respectively. The detection sensitivity, specificity, and accuracy of membrane-arrays for CTCs with KRAS oncogene were 84.4%, 95.3%, and 90.8%, respectively, and indeed a highly significant correlation to KRAS mutations in tumors (P < 0.0001) was observed. Forty-five (59.2%) patients responded to cetuximab plus chemotherapy, and 41 and 40 were wild-type KRAS in tumors and peripheral blood, respectively (both P < 0.0001). Patients with tumors that harbor wild-type KRAS are more likely to have a better progression-free survival and overall survival when treated with cetuximab plus chemotherapy (P < 0.0001). Likewise, patients with CTCs of wild-type KRAS in peripheral blood express a better progression-free survival and overall survival when treated with cetuximab plus chemotherapy (P < 0.0001).These findings provide evidence that detection of KRAS mutational status in CTCs, by gene expression array, has potential for clinical application in selecting metastatic colorectal cancer patients most likely to benefit from cetuximab therapy.
The IgLON Family in Epithelial Ovarian Cancer: Expression Profiles and Clinicopathologic Correlates
Authors: Evangelos Ntougkos, Robert Rush, Diane Scott, Tobias Frankenberg, Hani Gabra, John F. Smyth, Grant C. Sellar
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The IgLON family of cell adhesion molecules, comprising OPCML, HNT, LSAMP, and NEGR1, has recently been linked to cancer, through two of its members being proposed as tumor suppressors. We examined the expression profile of the family in human sporadic epithelial ovarian cancer and the normal ovary. Experimental Design: We determined the expression level of each IgLON in a panel comprising 57 tumor and 11 normal ovarian samples by quantitative real-time reverse transcription-PCR. The results were statistically tested for associations with clinicopathologic variables. Results: OPCML, LSAMP and NEGR1 exhibited reduced expression in the tumor samples relative to the normal samples, whereas HNT expression was elevated. Statistically significant changes were specific to histologic type. The expression levels of individual IgLONs were correlated, the most significant finding being a positive correlation between LSAMP and NEGR1. LSAMP expression was also negatively correlated with overall survival and was found to be a negative predictor of outcome. Conclusions: The expression of the IgLON family is altered in sporadic epithelial ovarian tumors in comparison to the normal ovary. In our small but representative cohort of patients, we have found significant correlations and associations in expression and clinicopathology that suggest a wider role of the family in ovarian cancer.
Treatment of Postsurgical Thromboembolic Complications
Authors: Per H. Langsjoen
Journal: JAMA (1971)

Under randomized and controlled conditions, 37 orthopedic patients at high risk from thromboembolic complications were given dextran 40 (Rheomacrodex), in a dose of about 1 gm/kg of body weight per 24 hours, for 52 hours after surgery because of its beneficial effect on red blood cell aggregation. The visible aggregation and the elevation of fibrinogen level usually observed in these patients, as well as the incidence of thromboembolism, were found to be significantly reduced in the treated group when compared to in 36 controls. Dextran 40 proved to be useful in the prevention of postsurgical thromboembolism.
Body Surface Distribution of Equipotential Lines during Atrial Depolarization and Ventricular Repolarization
Authors: BRUNO TACCARDI
Journal: Circulation Research (1966)

In 15 normal male human subjects and 6 dogs, 200 chest electrocardiograms were sequentially recorded. The distribution of equipotential lines on the thoracic surface was determined at 20 to 30 instants of time during atrial activation and ventricular recovery. In humans, the potential pattern is constantly dipolar, with one maximum and one minimum, during the P wave. The motion of the potential maximum and minimum on the chest surface appears to be related to the progress of the excitation through the auricular walls. At the end of the QRS interval, the simultaneous presence of activation and recovery potentials is generally observed, giving rise to several simultaneous maxima and minima. During the ST and T interval, recovery potentials show a dipolar distribution in normal subjects, but tripolar patterns are observed when the recovery process is altered in a circumscribed myocardial region. In dogs, multipolar distributions are frequently observed during the P wave, the ST segment and the T wave. During atrial activation and ventricular recovery, chest maps yield more information on the electrical activity of the heart (both normal and abnormal) than is offered by ordinary limb and precordial leads.
Analysis of the <i>RET</i>,<i>GDNF</i>, <i>EDN3</i>, and<i>EDNRB</i> genes in patients with intestinal neuronal dysplasia and Hirschsprung disease
Authors: R Gath, A Goessling, K-M Keller, S Koletzko, W Coerdt, H Müntefering, S Wirth, R M W Hofstra, L Mulligan, C Eng, A von Deimling
Journal: Gut (2001)

BACKGROUND Hirschsprung disease (HSCR) is a frequent congenital disorder with an incidence of 1 in 5000 live births, characterised by the absence of parasympathetic intramural ganglion cells in the hindgut resulting in intestinal obstruction in neonates and severe constipation in infants and adults. Intestinal neuronal dysplasia (IND) shares clinical features with HSCR but the submucosal parasympathetic plexus is affected. IND has been proposed as one of the most frequent causes of chronic constipation and is often associated with HSCR. METHODS We examined 29 patients diagnosed with sporadic HSCR, 20 patients with IND, and 12 patients with mixed HSCR/IND for mutations in the coding regions of the RET , GDNF , EDNRB , and EDN3 genes. The entire coding regions were analysed by single strand conformational polymorphism and DNA sequencing. RESULTS Only three RET mutations were detected in patients with HSCR. In patients with IND or a mixed HSCR/IND phenotype, no mutations in these genes were observed. While HSCR and HSCR/IND showed over representation of a specific RET polymorphism in exon 2, IND exhibited a significantly lower frequency comparable with that of controls. CONCLUSIONS The mutation frequency found in our sporadic HSCR patients (10%) and the allelic distribution of RET polymorphisms are comparable with earlier published data. A significantly different allelic distribution in an established HSCR associated polymorphism argues against common genetic pathways for HSCR and IND.