tbuckley/cabot-search huggingface dataset:
THE INSULIN RESISTANCE SYNDROME: Definition and Dietary Approaches to Treatment
Authors: Gerald M. Reaven
Journal: Annual Review of Nutrition (2005)

The ability of insulin to stimulate glucose disposal varies at least sixfold in apparently healthy individuals, and approximately one-third of the population that is most resistant to this action of insulin is at greatly increased risk to develop a number of adverse clinical outcomes. Type 2 diabetes occurs when insulin resistant individuals are unable to secrete enough insulin to compensate for the defect in insulin action, and this was the first clinical syndrome identified as being related to insulin resistance. Although the majority of insulin-resistant individuals are able to maintain the level of compensatory hyperinsulinemia needed to prevent the development of a significant degree of hyperglycemia, the combination of insulin resistance and hyperinsulinemia greatly increases the likelihood of developing a cluster of closely related abnormalities and the resultant clinical diagnoses that can be considered to make up the insulin resistance syndrome (IRS). Since being overweight/obese and sedentary decreases insulin sensitivity, it is not surprising that the prevalence of the manifestations of the IRS is increasing at a rapid rate. From a dietary standpoint, there are two approaches to attenuating the manifestations of the IRS: (a) weight loss to enhance insulin sensitivity in those overweight/obese individuals who are insulin resistant/hyperinsulinemic; and (b) changes in macronutrient content of diets to avoid the adverse effects of the compensatory hyperinsulinemia. This chapter will focus on defining the abnormalities and clinical syndromes that compose the IRS and evaluating the dietary changes that can ameliorate its adverse consequences.
Revising consensus in portal hypertension: Report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension
Authors: Roberto de Franchis
Journal: Journal of Hepatology (2010)

Stage of portal vein thrombosisJournal of HepatologyVol. 54Issue 5PreviewSimilar to previous recommendations [1–3], a stage-dependent therapeutic strategy of non-malignant and non-cirrhotic portal vein thrombosis (PVT) is advocated in the recent Baveno V consensus [4]. At recent or acute stage of PVT, the predominant goals of treatment are to maximize the rate of portal vein recanalization and to prevent thrombus extension upstream into the superior mesenteric vein and its possible secondary intestinal infarction. At the old or chronic stage, the primary therapeutic objectives are shifted to the prevention and treatment of variceal bleeding and management of portal biliopathy. Full-Text PDF Open Access
HIV gp120 induces endothelial dysfunction in tumour necrosis factor-α-activated porcine and human endothelial cells
Authors: Jun Jiang, Weiping Fu, Xinwen Wang, Peter H. Lin, Qizhi Yao, Changyi Chen
Journal: Cardiovascular Research (2010)

The aim of this study was to determine direct effects and potential molecular mechanisms of HIV gp120, a viral envelope glycoprotein, on endothelial function. Fresh porcine coronary artery rings and human coronary artery endothelial cells (HCAECs) were treated with recombinant HIV gp120 for 16 h with or without pretreatment with tumour necrosis factor-alpha (TNF-α) (8 h). With a myograph tension analysis, HIV gp120 with TNF-α pretreatment significantly decreased endothelium-dependent vasorelaxation in response to bradykinin in porcine coronary artery rings compared with untreated control vessels. In addition, HIV gp120 with TNF-α pretreatment significantly reduced endothelial nitric oxide synthase (eNOS) expression—both mRNA and protein levels—in porcine coronary artery rings and HCAECs compared with untreated controls. Furthermore, TNF-α pretreatment substantially increased intercellular adhesion molecule-1 (ICAM-1) expression in artery rings and HCAECs. Anti-gp120 or anti-ICAM-1 antibody significantly blocked these effects of HIV gp120. Silencing of ICAM-1 by siRNA oligonucleotides significantly blocked the effect of gp120 on eNOS downregulation in TNF-α-pretreated HCAECs. HIV gp120 and TNF-α synergistically reduce eNOS expression and cause endothelial dysfunction in both porcine coronary arteries and HCAECs. ICAM-1 induced by TNF-α pretreatment may mediate HIV gp120-induced endothelial dysfunction, which suggests a novel molecular mechanism of HIV gp120–ICAM-1 interaction inducing endothelial dysfunction.
Does a Clinical Trial Warrant an Economic Analysis?
Authors: Bruce E. Hillner, Thomas J. Smith
Journal: JNCI Journal of the National Cancer Institute (1998)

In all areas of medicine, clinicians feel under assault from multiple directions on how to reduce or limit health care costs. In the rush to control costs, the term ‘‘cost-effective’’ is commonly used by a wide spectrum of hospital administrators, pharmacists, private sector and government officials, and clinicians. As Doubilet et al. (1) first noted over a decade ago, the term ‘‘cost-effectiveness’’ is commonly misused, and often the user makes implicit assumptions about patient benefit without acknowledging that cost-effectiveness reflects a ratio of financial costs per unit of benefit. There has also been a marked growth in the number of economic evaluations of individual medications; many of these evaluations are sponsored by the pharmaceutical manufacturer. Such analyses fill a need of all interested parties but have the potential for biases in their conduct and reporting. This has been a long-standing concern of the field’s investigators who have responded by preparing guidelines for what should be included in such reports (2‐4).These principles have been applied in critiquing our own published work and are an integral part of our efforts as members of the Cancer and Leukemia Group B and the National Cancer Institute‐American Society of Clinical Oncology to integrate prospective economic analysis into clinical trials (5‐7). In this issue of the Journal, Rubino et al. (8) from France report a retrospective, cost-minimization economic analysis addressing the role of a hematopoietic growth factor in support of chemotherapy for non-Hodgkin’s lymphoma in children. Of the three types of economic analyses, they report a costminimization assessment that is relatively easy to do and to interpret, since no trade-offs are required in the interpretation of results. That is, the strategy is based on the premise that the lowest costs should be universally preferred; in a costeffectiveness or a cost-utility analysis, the acceptable ‘‘threshold’’ varies with one’s perspective. We suggest that the reader first consider if there was a compelling case for doing an economic analysis, then scrutinize the technical performance and completeness of the assessment, and finally interpret the results and their transportability to one’s own care setting. Treatment of childhood non-Hodgkin’s lymphoma has been
High- versus low-dose ACE inhibition in chronic heart failure
Authors: Dirk J van Veldhuisen, Sabine Genth-Zotz, Jan Brouwer, Frans Boomsma, Tilo Netzer, Arie J Man in ’t Veld, Yigal M Pinto, K.I Lie, Harry J.G.M Crijns
Journal: Journal of the American College of Cardiology (1998)
Giant Ulcers of the Transverse Colon
Authors: V. Samy Naiken
Journal: JAMA (1971)

<h3>To the Editor.—</h3> Giant ulcers of the colon are rare, and when present are sometimes associated with, or caused by, steroid medication.<sup>1</sup>In the case to be briefly reported, no specific etiological agent could be identified. As we have been unable to find any helpful information on discrete colonic ulcers from a recently published book on the pathology of the alimentary canal,<sup>2</sup>we wonder if your readers have encountered similar cases or have any views on the matter. <h3>Report of a Case.—</h3> A 72-year-old hypertensive woman, receiving hydrochlorothiazide medication for five years, was hospitalized in January 1971 with hoarseness, rectal bleeding, and anemia. Sigmoidoscopy revealed a small benign rectal ulcer which was biopsied. Because of continued bleeding, the rectum was again inspected and biopsy again showed acute and chronic nonspecific ulceration. A barium enema disclosed what was interpreted as a carcinoma of the transverse colon. A transverse colectomy
FDG PET for Diagnosing Infection in Hip and Knee Prostheses
Authors: Sandip Basu, Thomas C. Kwee, Babak Saboury, Jonathan P. Garino, Charles L. Nelson, Hongming Zhuang, Molly Parsons, Wengen Chen, Rakesh Kumar, Ali Salavati, Thomas J. Werner, Abass Alavi
Journal: Clinical Nuclear Medicine (2014)

This study aims to assess and compare the value of FDG PET with combined In-labeled leukocyte/Tc-sulfur colloid bone marrow (WBC/BM) imaging for diagnosing infection in hip and knee prostheses.In this prospective study, patients with painful hip or knee arthroplasty, who were scheduled to undergo clinical and diagnostic evaluation for prosthesis revision, were included. They have been studied by using FDG PET and WBC/BM scan. This study was institutional review board approved and Health Insurance Portability and Accountability Act compliant. All patients provided written informed consent.A total of 134 hip and 87 knee prostheses, suspected of being either infected or noninfectious loosening, were evaluated. All 221 prostheses underwent FDG PET, whereas both WBC/BM imaging and FDG PET were performed in 88 prostheses. The initial analysis of data from the WBC/BM images demonstrated somewhat suboptimal results compared with those of FDG PET scans on 88 patients. In addition, some patients were not willing to undergo both procedures and therefore participate in this study. Therefore, a decision was made to eliminate WBC/BM imaging from the procedures for the remainder of this research study. This decision was reached partly because of the significant radiation dose delivered from labeled WBC and safety issues related to preparing these labeled cells. Final diagnosis was based on microbiological examinations of the surgical specimens in 125 prostheses and joint aspirations combined with the clinical follow-up of 6 months or more in 86 prostheses. The sensitivity, specificity, positive predictive value, and negative predictive value of FDG PET in hip prostheses were 81.8%, 93.1%, 79.4%, and 94.0%, respectively, and in knee prostheses were 94.7%, 88.2%, 69.2%, and 98.4%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of WBC/BM imaging in hip prostheses were 38.5%, 95.7%, 71.4%, and 84.6%, respectively, and in knee prostheses were 33.3%, 88.5%, 25.0%, and 92.0%, respectively. In those cases that underwent both FDG PET and WBC/BM imaging, there was a trend (P = 0.0625) toward a higher sensitivity for FDG PET in hip prostheses, whereas other comparisons did not show any significant differences between the 2 imaging modalities.Based on this study, the diagnostic performance of FDG PET scan in detecting infection in painful hip and knee prostheses is optimal for routine clinical application. Considering the complexity and costs of WBC/BM imaging and related safety issues associated with this preparation, FDG PET seems to be an appropriate alternative for assessing these patients.
A seven-gene signature (cirrhosis risk score) predicts liver fibrosis progression in patients with initially mild chronic hepatitis C
Authors: Moira Marcolongo, Bradford Young, Francesca Dal Pero, Giovanna Fattovich, Laura Peraro, Maria Guido, Giada Sebastiani, Giorgio Palù, Alfredo Alberti
Journal: Hepatology (2009)

Fibrosis progression is the main determinant of liver disease outcome in chronic hepatitis C, being influenced by environmental and host factors. Recently, a cirrhosis risk score (CRS) based on seven single-nucleotide polymorphisms was proposed as genetic predictor of cirrhosis in hepatitis C. To assess the role of CRS in predicting fibrosis progression in patients with initially no or minimal to moderate fibrosis, we investigated 271 untreated patients with chronic hepatitis C having initial liver biopsy showing METAVIR stage F0 (n = 104), F1 (n = 101), or F2 (n = 59) who had been followed up without antiviral therapies for at least 60 months (mean 108.5 +/- 71.5 months) and had a liver biopsy at the end of this observation period. Of these, 24.4% showed no histologic progression, 75.6% progressed by at least one stage, 45.0% progressed by at least two stages, and 10.3% progressed by more than two stages. The mean CRS was significantly higher (P = 0.005) in patients with fibrosis progression compared with those without progression, and this difference was particularly evident (P = 0.002) with F0 on initial biopsy. Mean CRS scores were not associated with degree of fibrosis progression. The relative risk of fibrosis progression increased with increasing CRS values. This association was significant in males but not in females and was most evident in males with F0 at initial biopsy (odds ratio 16.5, 95% confidence interval 1.6-166; P= 0.02) in the presence of high CRS. Multivariate analysis confirmed the significant association of CRS score with fibrosis progression. The predictive value of CRS was confirmed in hepatitis C virus patients admitting significant alcohol intake.Host genetics defined by CRS predict fibrosis progression in males with initially mild chronic hepatitis C and may become a useful parameter for prognostic evaluation and treatment decision.
Virgin Care is set to take over two NHS community health services in Surrey
Authors: A. O'Dowd
Journal: BMJ (2012)

Private firm Virgin Care is to take over running NHS community health services in two parts of Surrey in a £500m (€605m; $791m) deal agreed with the local primary care trust.

Unions and campaigning groups have reacted angrily to the development which they see as proof of the government’s intention to allow private companies a much greater role in the NHS so soon after the controversial NHS changes became law in the Health and Social Care Act ( BMJ 2012;344,:e2243, doi:10.1136/bmj.e2243).

NHS Surrey has announced it has signed a contract with Virgin Care (formerly Assura Medical) to deliver community services across much of the county from 2012 to 2017 including community nursing, health visiting, physiotherapy, diabetes …
Markers, Markers Everywhere . . . . . Prognosis in Colorectal Cancer—Time for a New Approach
Authors: Jervoise Andreyev, David Cunningham
Journal: Journal of Clinical Oncology (2001)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.2.286 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11208817 Markers, Markers Everywhere . . . . . Prognosis in Colorectal Cancer—Time for a New Approach Jervoise AndreyevxJervoise AndreyevSearch for articles by this author David CunninghamxDavid CunninghamSearch for articles by this author Show More Imperial College School of Medicine, London, United KingdomRoyal Marsden Hospital, London, United Kingdom https://doi.org/10.1200/JCO.2001.19.2.286 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
Interaction of asialo von Willebrand factor with glycoprotein Ib induces fibrinogen binding to the glycoprotein IIb/IIIa complex and mediates platelet aggregation.
Authors: L De Marco, A Girolami, S Russell, Z M Ruggeri
Journal: Journal of Clinical Investigation (1985)

von Willebrand factor (vWF) is necessary for the initial attachment of platelets to exposed subendothelium, particularly under flow conditions like those prevailing in the microcirculation. Little is known about its possible participation in subsequent events leading to formation of platelet thrombi at sites of vascular injury. We addressed this question by studying the mechanisms by which desialylated vWF induces platelet aggregation in the absence of any other stimulus. Asialo vWF, unlike the native molecule, does not require ristocetin to interact with platelets. Agglutination induced by ristocetin is largely independent of active platelet metabolism and only partially reflects physiological events. We have shown here that binding of asialo vWF to platelets was accompanied by release of dense granule content and subsequent ADP-dependent fibrinogen binding to receptors on the glycoprotein (GP) IIb/IIIa complex. The initial interaction of asialo vWF with platelets was mediated by GPIb, as shown by blocking obtained with monoclonal antibody. Inhibition of this initial interaction completely abolished platelet aggregation induced by asialo vWF. The same effect was obtained with a monoclonal anti-GPIIb/IIIa antibody. This, however, did not block asialo vWF binding to platelets, but rather inhibited subsequent fibrinogen binding induced by asialo vWF. Therefore, the latter process was also essential for platelet aggregation under the conditions described. At saturation, asialo vWF induced binding of between 3.2 and 27.7 X 10(3) fibrinogen molecules/platelet, with an apparent dissociation constant between 0.28 and 1.18 X 10(-6) M. This study shows that asialo, and possibly native, vWF acts as a platelet agonist after its binding to GPIb and induces aggregation through a pathway dependent on GPIIb/IIIa-related receptors.
PREVALENCE OF FABRY DISEASE IN KOREAN MALE PATIENTS WITH LEFT VENTRICULAR HYPERTROPHY
Authors: Woo-Shik Kim, Toshihiro Takenaka, Bang Hun Lee, Soon Pyo Hong, Jong Chun Park, Jin-Won Jeong, Jae Ki Ko, Kyung Hoon Choe, Jae Hyung Kim, Namsik Chung, Han-Wook Yoo, Chuwa Tei, Jong-Hoa Bae
Journal: Journal of the American College of Cardiology (2010)
Misexpression of Full-length HMGA2 Induces Benign Mesenchymal Tumors in Mice
Authors: M. Raza Zaidi, Yasunori Okada, Kiran K. Chada
Journal: Cancer Research (2006)

Abstract The high-mobility group AT-hook 2 (HMGA2) protein is a member of the high-mobility group family of the DNA-binding architectural factors and participates in the conformational regulation of active chromatin on its specific downstream target genes. HMGA2 is expressed in the undifferentiated mesenchyme and is undetectable in their differentiated counterparts, suggesting its functional importance in mesenchymal cellular proliferation and differentiation. Interestingly, it is a frequent target of chromosomal translocations in several types of human benign differentiated mesenchymal tumors, including lipomas, fibroadenomas of the breast, salivary gland adenomas, and endometrial polyps. The translocations lead to a variety of HMGA2 transcripts, which range from wild-type, truncated, and fusion mRNA species. However, it is not clear whether alteration of the HMGA2 transcript is required for its tumorigenic potential. To determine whether misexpression of HMGA2 in differentiated mesenchymal cells is sufficient to cause tumorigenesis, we produced transgenic mice that misexpressed full-length or truncated human HMGA2 transcript under the control of the differentiated mesenchymal cell (adipocyte)–specific promoter of the adipocyte P2 (Fabp4) gene. Expression of the full-length HMGA2 transgene was observed in a number of tissues, which produced neoplastic phenotype, including fibroadenomas of the breast and salivary gland adenomas. Furthermore, transgenic misexpression of the truncated version of HMGA2, containing only the three DNA-binding domains, produced similar phenotypes. These results show that misexpression of HMGA2 in a differentiated mesenchymal cell is sufficient to cause mesenchymal tumorigenesis and is independent of the nature of the HMGA2 transcript that results from chromosomal translocations observed in humans. (Cancer Res 2006; 66(15): 7453-9)
The Sweet Contraceptive
Authors: Henry T. Ricketts
Journal: JAMA (1975)

What would couples, married or not, give for a chemical anticonceptive that is taken by mouth, as now; that does not involve counting days (or beads); that retains normal libido; that, when withheld for a time, does not interfere with procreation; and that is nontoxic in effective doses? And (the icing on the cake), a preparation for men only?  Alas, man cannot yet reach this Elysium, but certain mice are already there. Our intelligence comes from Thomas H. Maugh, II, a reporter for Science , who summarizes the experiments of Roy L. Whistler, John R. Zysk, Alfred A. Bushway, and William W. Carlton of Purdue University.  The story begins with the fact that testicular cells depend, among other things, on D-glucose for the manufacture of sperm. Some years ago, for some reason, Whistler managed to synthesize a compound, 5-thio-glucose, which, it turned out, is an inhibitor of spermatogenesis in mice. It
UGT1A and Irinotecan Toxicity: Keeping It in the Family
Authors: Janelle M. Hoskins, Howard L. McLeod
Journal: Journal of Clinical Oncology (2009)

Janelle M. Hoskins, Institute of Pharmacogenomics and Individualized Therapy; and Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC Howard L. McLeod, Institute of Pharmacogenomics and Individualized Therapy; Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy; and Division of Hematology and Oncology, Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina, Chapel Hill, NC
ABC of psychological medicine: Trauma
Authors: R. Mayou
Journal: BMJ (2002)

Minor trauma is a part of everyday life, and for most people these injuries are of only transient importance, but some have psychiatric and social complications. Most people experience major trauma at some time in their lives. Psychological, behavioural, and social factors are all relevant to the subjective intensity of physical symptoms and their consequences for work, leisure, and family life. As a result, disability may become greater than might be expected from the severity of the physical injuries. View this table: Lifetime prevalence of specific traumatic events (n=2181) Psychological and interpersonal factors also contribute to the cause of trauma, and clinicians should be alert to these and their implications for treatment. Tactful questioning, careful examination, and detailed record keeping are essential, especially for non-accidental injury by a patient or others: At a major incident it is important that members of the emergency services, especially ambulance staff and police, should seem calm and in control. This helps to relieve distress and prevent victims from suffering further injury. Explanation and encouragement can reduce fear at the prospect of being taken to hospital by ambulance. The needs of uninjured relatives and others involved should also be considered. Clearly recorded details of the incident, injury, and the extent of any loss of consciousness may be useful in later assessment as well as in the preparation of subsequent medicolegal reports. ### Immediate effects of frightening trauma