tbuckley/cabot-search huggingface dataset:
Evaluation and Management of Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2012 Clinical Practice Guideline
Authors: Paul E. Stevens
Journal: Annals of Internal Medicine (2013)

The Kidney Disease: Improving Global Outcomes (KDIGO) organization developed clinical practice guidelines in 2012 to provide guidance on the evaluation, management, and treatment of chronic kidney disease (CKD) in adults and children who are not receiving renal replacement therapy.The KDIGO CKD Guideline Development Work Group defined the scope of the guideline, gathered evidence, determined topics for systematic review, and graded the quality of evidence that had been summarized by an evidence review team. Searches of the English-language literature were conducted through November 2012. Final modification of the guidelines was informed by the KDIGO Board of Directors and a public review process involving registered stakeholders.The full guideline included 110 recommendations. This synopsis focuses on 10 key recommendations pertinent to definition, classification, monitoring, and management of CKD in adults.
Risk factors for coronary heart disease: implications of gender
Authors: J Roeters van Lennep
Journal: Cardiovascular Research (2002)

It has been recognized over the past years that women form a distinct subpopulation within patients with coronary heart disease. This phenomenon should be acknowledged in the management and in the assessment of coronary heart disease. Over the past years remarkable progress has been made concerning our knowledge of cardiovascular risk factors related to gender. For instance, diabetes, high density lipoproteins and triglycerides levels have been found to have a greater impact on coronary heart disease risk in women compared to men. On the other hand, evidence showing that lipoprotein (a) is a cardiovascular risk factor seems to be stronger in men than in women. For optimal treatment and prevention of coronary heart disease it is necessary to acknowledge that it is not self-evident that women and men show simular responses to risk factors or to treatment. This review article addresses the role of cardiovascular risk factors focusing on the differential impact they might have on men and women.
Phase I Study of Neratinib in Combination With Temsirolimus in Patients With Human Epidermal Growth Factor Receptor 2–Dependent and Other Solid Tumors
Authors: Leena Gandhi, Rastislav Bahleda, Sara M. Tolaney, Eunice L. Kwak, James M. Cleary, Shuchi S. Pandya, Antoine Hollebecque, Richat Abbas, Revathi Ananthakrishnan, Anna Berkenblit, Mizue Krygowski, Yali Liang, Kathleen W. Turnbull, Geoffrey I. Shapiro, Jean-Charles Soria
Journal: Journal of Clinical Oncology (2013)

Purpose Human epidermal growth factor (HER) –mediated signaling is critical in many cancers, including subsets of breast and lung cancer. HER family members signal via the phosphatidylinositide 3-kinase (PI3K) –AKT/protein kinase B–mammalian target of rapamycin (mTOR) cascade; mTOR activation is critical for the expression of multiple contributors to tumor growth and invasion. On the basis of preclinical data suggesting synergy of HER2 inhibition and mTOR inhibition in breast and lung cancer models, we conducted a phase I combination study of neratinib, a small-molecule irreversible pan-HER tyrosine kinase inhibitor, and temsirolimus, an mTOR inhibitor, in patients with advanced solid tumors. Patients and Methods This study enrolled patients to dosing combinations of neratinib and temsirolimus. The primary objective was to estimate the toxicity contour of the combination and establish recommended phase II doses. Results Sixty patients were treated on 12 of 16 possible dosing combinations. Diarrhea was the most common drug-related (93%) and dose-limiting toxicity (DLT), constituting four of 10 DLTs. Dose-limiting grade 3 metabolic abnormalities were also observed. Other frequent drug-related toxicities included nausea, stomatitis (both 53%), and anemia (48%). Two maximum-tolerated dose combinations were identified: 200 mg of neratinib/25 mg of temsirolimus and 160 mg of neratinib/50 mg of temsirolimus. Responses were noted in patients with HER2-amplified breast cancer resistant to trastuzumab, HER2-mutant non–small-cell lung cancer, and tumor types without identified mutations in the HER-PI3K-mTOR pathway. Conclusion The combination of neratinib and temsirolimus was tolerable and demonstrated antitumor activity in multiple tumor types, warranting further evaluation.
The Utopian Medicine of H. G. Wells
Authors: Frank R. Freemon
Journal: JAMA (1970)

H.G. Wells (1866-1946) rose from the lower rungs of stratified Victorian English society to become an elder of science fiction, a remarkable predictor of developments in biology and warfare, and a great popularizer of history and science. Over the years, this extremely prolific writer offered several versions of the Utopia that he desired for mankind, and his extensive knowledge of biological science gave depth and emphasis to the medical aspects of his Utopia. If we review Wells' expectations of Utopian health care systems we may see in perspective the expectations of modern society. Herbert George Wells, son of Joseph Wells, a shopkeeper and gardener, and Sarah Neals Wells, a lady's maid, was born in 1866 in Bromley, Kent, a country village that during Wells' childhood was absorbed into London suburbia. An avid reader as a child, Wells balked at the apprenticeship and drab working life that had swallowed his two
Angiotensin II–dependent TGF-β signaling contributes to Loeys-Dietz syndrome vascular pathogenesis
Authors: Elena M. Gallo, David C. Loch, Jennifer P. Habashi, Juan F. Calderon, Yichun Chen, Djahida Bedja, Christel van Erp, Elizabeth E. Gerber, Sarah J. Parker, Kimberly Sauls, Daniel P. Judge, Sara K. Cooke, Mark E. Lindsay, Rosanne Rouf, Loretha Myers, Colette M. ap Rhys, Kathleen C. Kent, Russell A. Norris, David L. Huso, Harry C. Dietz
Journal: Journal of Clinical Investigation (2013)

Loeys-Dietz syndrome (LDS) is a connective tissue disorder that is characterized by a high risk for aneurysm and dissection throughout the arterial tree and phenotypically resembles Marfan syndrome. LDS is caused by heterozygous missense mutations in either TGF-β receptor gene (TGFBR1 or TGFBR2), which are predicted to result in diminished TGF-β signaling; however, aortic surgical samples from patients show evidence of paradoxically increased TGF-β signaling. We generated 2 knockin mouse strains with LDS mutations in either Tgfbr1 or Tgfbr2 and a transgenic mouse overexpressing mutant Tgfbr2. Knockin and transgenic mice, but not haploinsufficient animals, recapitulated the LDS phenotype. While heterozygous mutant cells had diminished signaling in response to exogenous TGF-β in vitro, they maintained normal levels of Smad2 phosphorylation under steady-state culture conditions, suggesting a chronic compensation. Analysis of TGF-β signaling in the aortic wall in vivo revealed progressive upregulation of Smad2 phosphorylation and TGF-β target gene output, which paralleled worsening of aneurysm pathology and coincided with upregulation of TGF-β1 ligand expression. Importantly, suppression of Smad2 phosphorylation and TGF-β1 expression correlated with the therapeutic efficacy of the angiotensin II type 1 receptor antagonist losartan. Together, these data suggest that increased TGF-β signaling contributes to postnatal aneurysm progression in LDS.
Methods, Successes, and Failures of Smoking Cessation Programs
Authors: Edwin B Fisher, Edward Lichtenstein, Debra Haire-Joshu, Glen D. Morgan, Heather R. Rehberg
Journal: Annual Review of Medicine (1993)

Addictive and conditioning processes interact to make cigarette smoking a common, lethal behavior that is highly resistant to change. In addition to addiction and conditioning, smoking is maintained by a wide range of forces, ranging from social modeling and advertising to the politics and economics of international trade. Parallel to this wide range of causes of smoking, interventions to encourage smoking cessation range from simple information and suggestions to smoking cessation classes, to nicotine replacement, to community or national campaigns that promote nonsmoking. Clinicians can make contributions throughout this range of activities, from the consulting room to political advocacy. While no one of these is highly successful on its own, together they have prompted almost 50% of smokers to quit, an impressive accomplishment.
Cardiac Myocytes Activated by Septic Plasma Promote Neutrophil Transendothelial Migration
Authors: W. Sean Madorin, Tao Rui, Naohito Sugimoto, Osamu Handa, Gediminas Cepinskas, Peter R. Kvietys
Journal: Circulation Research (2004)

Cardiac myocytes isolated from rats with peritonitis (cecal ligation and perforation; CLP) promote PMN transendothelial migration. Herein, we assessed (1) the mechanisms involved in cardiac myocyte activation during peritonitis and (2) the means by which these activated myocytes promote PMN transendothelial migration. Plasma obtained from mice subjected to CLP (septic plasma) activated isolated cardiac myocytes as evidenced by (1) increased nuclear levels of nuclear factor-kappaB (NF-kappaB) and (2) their ability to promote PMN migration across endothelial cell monolayers. Pretreatment of septic plasma with an antibody against tumor necrosis factor-alpha (TNF-alpha), but not interleukin-1beta (IL-1beta), blunted the ability of septic plasma to activate the myocytes. However, septic plasma obtained from TNF-alpha-deficient mice could still activate the myocytes; an effect attenuated by an antibody against IL-1beta. If the myocytes were pretreated with a proteasome inhibitor (MG 132) to prevent NF-kappaB activation, the myocyte-induced PMN transendothelial migration was compromised. The activated myocytes released platelet-activating factor (PAF), and myocyte-induced PMN migration was abrogated by a PAF receptor antagonist (WEB 2086). These myocytes also released the CXC chemokines LIX and KC; an event prevented by MG 132. Antibodies against LIX and KC abrogated the myocyte-induced PMN migration. However, LIX and KC, but not PAF, could promote PMN migration when used at concentrations produced by activated myocytes. These observations indicate that TNF-alpha and IL-1beta are, in part, responsible for the ability of septic plasma to activate cardiac myocytes. The activated myocytes promote PMN transendothelial migration, an effect attributable to LIX and KC, and possibly, PAF.
AHI1 is required for photoreceptor outer segment development and is a modifier for retinal degeneration in nephronophthisis
Authors: Carrie M Louie, Gianluca Caridi, Vanda S Lopes, Francesco Brancati, Andreas Kispert, Madeline A Lancaster, Andrew M Schlossman, Edgar A Otto, Michael Leitges, Hermann-Josef Gröne, Irma Lopez, Harini V Gudiseva, John F O'Toole, Elena Vallespin, Radha Ayyagari, Carmen Ayuso, Frans P M Cremers, Anneke I den Hollander, Robert K Koenekoop, Bruno Dallapiccola, Gian Marco Ghiggeri, Friedhelm Hildebrandt, Enza Maria Valente, David S Williams, Joseph G Gleeson
Journal: Nature Genetics (2010)
Assessment of Group Versus Individual Diabetes Education
Authors: Patti. L. Rickheim, Todd W. Weaver, Jill. L. Flader, David. M. Kendall
Journal: Diabetes Care (2002)

OBJECTIVES— The current study was conducted to compare the effectiveness of delivering diabetes education in either a group or individual setting using a consistent, evidence-based curriculum. RESEARCH DESIGN AND METHODS— A total of 170 subjects with type 2 diabetes were randomly assigned to either group (n = 87) or individual (n = 83) educational settings. Subjects received education in four sequential sessions delivered at consistent time intervals over a 6-month period. Outcomes included changes in knowledge, self-management behaviors, weight, BMI, HbA1c, health-related quality of life, patient attitudes, and medication regimen. Changes were assessed at baseline and after the 2-week, 3-month, and 6-month education sessions. RESULTS— Both educational settings had similar improvements in knowledge, BMI, health-related quality of life, attitudes, and all other measured indicators. HbA1c decreased from 8.5 ± 1.8% at baseline to 6.5 ± 0.8% at 6 months (P &amp;lt; 0.01) in the study population as a whole. Subjects assigned to the individual setting had a 1.7 ± 1.9% reduction in HbA1c (P &amp;lt; 0.01), whereas subjects assigned to the group setting had a 2.5 ± 1.8% reduction in HbA1c (P &amp;lt; 0.01). The difference in HbA1c improvement was marginally greater in subjects assigned to group education versus individualized education (P = 0.05). CONCLUSIONS— This study demonstrates that diabetes education delivered in a group setting, when compared with an individual setting, was equally effective at providing equivalent or slightly greater improvements in glycemic control. Group diabetes education was similarly effective in delivering key educational components and may allow for more efficient and cost-effective methods in the delivery of diabetes education programs.
LIGHT, a New Member of the TNF Superfamily, and Lymphotoxin α Are Ligands for Herpesvirus Entry Mediator
Authors: Davide N Mauri, Reinhard Ebner, Rebecca I Montgomery, Kristine D Kochel, Timothy C Cheung, Guo-Liang Yu, Steve Ruben, Marianne Murphy, Roselyn J Eisenberg, Gary H Cohen, Patricia G Spear, Carl F Ware
Journal: Immunity (1998)

Herpes simplex virus (HSV) 1 and 2 infect activated T lymphocytes by attachment of the HSV envelope glycoprotein D (gD) to the cellular herpesvirus entry mediator (HVEM), an orphan member of the tumor necrosis factor receptor superfamily. Here, we demonstrate that HVEM binds two cellular ligands, secreted lymphotoxin α (LTα) and LIGHT, a new member of the TNF superfamily. LIGHT is a 29 kDa type II transmembrane protein produced by activated T cells that also engages the receptor for the LTαβ heterotrimer but does not form complexes with either LTα or LTβ. HSV1 gD inhibits the interaction of HVEM with LIGHT, and LIGHT and gD interfere with HVEM-dependent cell entry by HSV1. This characterizes herpesvirus gD as a membrane-bound viokine and establishes LIGHT-HVEM as integral components of the lymphotoxin cytokine-receptor system.8 These authors made equal contributions.
Mortality in severe sleep apnoea/hypopnoea syndrome patients: impact of treatment
Authors: S. Marti, G. Sampol, X. Muñoz, F. Torres, A. Roca, P. Lloberes, T. Sagalés, P. Quesada, F. Morell
Journal: European Respiratory Journal (2002)

The aim of this study was to determine mortality in patients with sleep apnoea/hypopnoea syndrome (SAHS) according to the treatments employed and comorbidity. An historical cohort of patients with SAHS diagnosed at a university hospital between 1982 and 1992 and followed until 1996 was studied. From a total of 475 SAHS patients, 444 (94%), with a mean+/-SD apnoea/hypopnoea index at diagnosis of 55+/-27, were located and included in the study. SAHS treatments employed were: surgery (88), weight loss (134), continuous positive airway pressure (124) and 98 patients were not treated. By the end of follow-up, 49 patients had died. According to Cox regression analysis, mortality in treated patients was lower than in those not treated, but higher in those with a history of severe chronic obstructive pulmonary disease. Mortality in nontreated patients compared with that of the general population, adjusted for age and sex, showed excessive mortality, which decreased in treated patients. Stratification by age showed a greater mortality rate ratio in patients <50 yrs. These findings were maintained when mortality from cardiovascular causes was compared. In conclusion, a rise in mortality was found in nontreated sleep apnoea/hypopnoea syndrome patients compared with the general population, whereas mortality in those treated for sleep apnoea/hypopnoea syndrome did not differ significantly from that of the general population.
Less is More: Not "Going the Distance" and Why
Authors: R. Harris, L. S. Kinsinger
Journal: JNCI Journal of the National Cancer Institute (2011)

Podolsky wrote an influential editorial in the New England Journal of Medicine entitled “Going the Distance—The Case for True Colorectal Cancer Screening” (1) in the year 2000. He advocated for a primary colonoscopy screening strategy, “going the distance,” and suggested that screening with flexible sigmoidoscopy was akin to screening only one breast for breast cancer. The seductive logic of screening is well known; Podolsky’s approach further extends that logic. The issue is not whether to screen but rather how to screen. Randomized controlled trials show that screening with fecal occult blood tests (FOBT) and flexible sigmoidoscopy reduces mortality from colorectal cancer (CRC), but there is much less evidence about the magnitude of any additional benefit from colonoscopy (2–6). The argument Podolsky makes is that if some screening is good, then more must be better. We need to “go the distance”—the entire distance—to maximize the benefit from screening. What was missing from his analysis was any attempt to weigh an additional benefit from colonoscopy against additional harm and to consider additional costs to individuals and society (7). Perhaps, we can get more from “going the distance,” but with what harms and at what cost? Podolosky’s editorial, together with other factors, had an enormous effect. The United States has indeed adopted a primary colonoscopy strategy for CRC screening (8), and this strategy is
Repair of traumatic aortic arch to innominate vein fistula under deep hypothermia and circulatory arrest.
Authors: D Astolfi, D di Carlo, G di Eusanio, C Marcelletti
Journal: Thorax (1976)

Penetrating injuries of the thoracic aorta are usually rapidly lethal. Few patients survive for long enough to undergo surgical treatment. When penetrating injuries of the thoracic aorta are complicated by arteriovenous fistula a correct preoperative diagnosis is important for adequate planning of the surgical repair, and so selective angiography is essential. The best approach is through a median sternotomy with the use of total cardiopulmonary bypass with or without deep hypothermia and circulatory arrest. Fistulae between aorta and innominate vein invariably lead to congestive cardiac failure. A review of the literature suggests that signs of cardiac failure rarely appear early. Congestive failure developed within 30 days of the initial trauma in only two of the 12 reported cases. In our case, the early onset of cardac failure refractory to therapy and the appearance of an expanding pulsatile mass at the base of the neck, threatening rupture, necessitated emergency surgical treatment.
Expressed sequence tag analysis in Cycas, the most primitive living seed plant
Authors: Eric D Brenner, Dennis W Stevenson, Richard W McCombie, Manpreet S Katari, Stephen A Rudd, Klaus FX Mayer, Peter M Palenchar, Suzan J Runko, Richard W Twigg, Guangwei Dai, Rob A Martienssen, Phillip N Benfey, Gloria M Coruzzi
Journal: Genome biology (2003)
Cytocidal Effect of Chloroform-Activated Serum on Ascites Tumor Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Charles A. Apffel
Journal: JNCI Journal of the National Cancer Institute (1963)

Normal, chloroform-activated human serum exerted a cytocidal effect on cells of the Ehrlich ascites carcinoma and the EL-4 leukosis. Serum complement was not required, but a previous chelation prevented chloroform-activated serum from having a cytocidal effect. Absorption of the serum with normal cells or with tumor cells before activation had no effect on activity. There was no consistent difference in cytocidal capability between serum from normal persons and that from cancer patients.
Vanilloid Receptor TRPV1, Sensory C-Fibers, and Vascular Autoregulation
Authors: Ramona S. Scotland, Sharmila Chauhan, Clare Davis, Carmen De Felipe, Stephen Hunt, Jahangir Kabir, Peter Kotsonis, Uhtaek Oh, Amrita Ahluwalia
Journal: Circulation Research (2004)

Myogenic constriction describes the innate ability of resistance arteries to constrict in response to elevations in intraluminal pressure and is a fundamental determinant of peripheral resistance and, hence, organ perfusion and systemic blood pressure. However, the receptor/cell-type that senses changes in pressure on the blood vessel wall and the pathway that couples this to constriction of vascular smooth muscle remain unclear. In this study, we show that elevation of intraluminal transmural pressure of mesenteric small arteries in vitro results in a myogenic response that is profoundly suppressed following ablation of sensory C-fiber activity (using in vitro capsaicin desensitization resulted in 72.8±10.3% inhibition, n=8; P &lt;0.05). Activation of C-fiber nerve endings by pressure was attributable to stimulation of neuronal vanilloid receptor, TRPV1, because blockers of this channel, capsazepine (71.9±11.1% inhibition, n=9; P &lt;0.001) and ruthenium red (46.1±11.7% inhibition, n=4; P &lt;0.05), suppressed the myogenic constriction. In addition, this C-fiber dependency is likely related to neuropeptide substance P release and activity because blockade of tachykinin NK 1 receptors (66.3±13.7% inhibition, n=6; P &lt;0.001), and not NK2 receptors (n=4, NS), almost abolished the myogenic response. Previous studies support a role for 20-hydroxyeicosatetraenoic acid (20-HETE) in myogenic constriction responses; herein, we show that 20-HETE–induced constriction of mesenteric resistance arteries is blocked by capsazepine. Together, these results suggest that elevation of intraluminal pressure is associated with generation of 20-HETE that, in turn, activates TRPV1 on C-fiber nerve endings resulting in depolarization of nerves and consequent vasoactive neuropeptide release. These findings identify a novel mechanism contributing to Bayliss’ myogenic constriction and highlights an alternative pathway that may be targeted in the therapeutics of vascular disease, such as hypertension, where enhanced myogenic constriction plays a role in the pathogenesis.
Identification of a genetic locus controlling bacteria-driven colitis and associated cancer through effects on innate inflammation
Authors: Olivier Boulard, Stefanie Kirchberger, Daniel J. Royston, Kevin J. Maloy, Fiona M. Powrie
Journal: The Journal of Experimental Medicine (2012)

Chronic inflammation of the intestine has been associated with an elevated risk of developing colorectal cancer. Recent association studies have highlighted the role of genetic predisposition in the etiology of colitis and started to unravel its complexity. However, the genetic factors influencing the progression from colon inflammation to tumorigenesis are not known. We report the identification of a genetic interval Hiccs that regulates Helicobacter hepaticus–induced colitis and associated cancer susceptibility in a 129.RAG−/− mouse model. The 1.7-Mb congenic interval on chromosome 3, containing eight genes and five microRNAs, renders susceptible mice resistant to colitis and reduces tumor incidence and multiplicity. Bone marrow chimera experiments showed that resistance is conferred by the hematopoietic compartment. Moreover, the Hiccs locus controls the induction of the innate inflammatory response by regulating cytokine expression and granulocyte recruitment by Thy1+ innate lymphoid cells. Using a tumor-promoting model combining chronic Helicobacter hepaticus infection and the carcinogen azoxymethane, we found that Hiccs also regulates the frequency of colitis-associated neoplasia. Our study highlights the importance of innate immune cells and their genetic configuration in driving progression from inflammation toward cancer and opens the door for analysis of these pathways in human inflammatory disorders and associated cancers.