tbuckley/cabot-search huggingface dataset:
Comparison of Neurocognitive Functioning in Children Previously Randomly Assigned to Intrathecal Methotrexate Compared With Triple Intrathecal Therapy for the Treatment of Childhood Acute Lymphoblastic Leukemia
Authors: Nina S. Kadan-Lottick, Pim Brouwers, David Breiger, Thomas Kaleita, James Dziura, Veronika Northrup, Lu Chen, Megan Nicoletti, Bruce Bostrom, Linda Stork, Joseph P. Neglia
Journal: Journal of Clinical Oncology (2009)

Purpose For the majority of children with acute lymphoblastic leukemia (ALL), CNS prophylaxis consists of either intrathecal (IT) methotrexate or triple IT therapy (ie, methotrexate with both cytarabine and hydrocortisone). The long-term neurotoxicities of these two IT strategies have not yet been directly compared. Patients and Methods In this multisite study, 171 children with standard-risk ALL, age 1 to 9.99 years at diagnosis, previously randomly assigned to IT methotrexate (n = 82) or to triple IT therapy (n = 89) on CCG 1952, underwent neurocognitive evaluation by a licensed psychologist at a mean of 5.9 years after random assignment. Results Patients who received IT methotrexate had a mean Processing Speed Index that was 3.6 points lower, about one fourth of a standard deviation, than those who received triple IT therapy (P = .04) after analysis was adjusted for age, sex, and time since diagnosis. Likewise, 19.5% of children in the IT methotrexate group had a Processing Speed Index score in the below-average range compared with 6.9% in the triple IT therapy group (P = .02). Otherwise, the groups performed similarly on tests of full-scale intelligence quotient, academic achievement, attention/concentration, memory, and visual motor integration. The association of treatment with measures of cognitive functioning was not modified by sex or age at diagnosis. In the post-therapy period, there were no group differences in special education services, neurologic events, or use of psychotropic medications. Conclusion This study did not show any clinically meaningful differences in neurocognitive functioning between patients previously randomly assigned to IT methotrexate or triple IT therapy except for a small difference in processing speed in the IT methotrexate group.
Computed tomographic appearance of an oleothorax.
Authors: B P Deboisblanc, W C Burch, H A Buechner, E F Haponik
Journal: Thorax (1988)

Sequelae of oleothorax, formerly used in the treatment of tuberculosis, may still be encountered. A patient is reported whose oleothorax, created 44 years previously, was demonstrated by computed tomography.
Localization of Inward Rectifier Potassium Channel Kir7.1 in the Basolateral Membrane of Distal Nephron and Collecting Duct
Authors: KAYOKO OOKATA, AKIHIRO TOJO, YOSHIRO SUZUKI, NOBUHIRO NAKAMURA, KENJIRO KIMURA, CHRISTOPHER S. WILCOX, SHIGEHISA HIROSE
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Inward rectifier potassium channels (Kir) play an important role in the K + secretion from the kidney. Recently, a new subfamily of Kir, Kir7.1, has been cloned and shown to be present in the kidney as well as in the brain, choroid plexus, thyroid, and intestine. Its cellular and subcellular localization was examined along the renal tubule. Western blot from the kidney cortex showed a single band for Kir7.1 at 52 kD, which was also observed in microdissected segments from the thick ascending limb of Henle, distal convoluted tubule (DCT), connecting tubule, and cortical and medullary collecting ducts. Kir7.1 immunoreactivity was detected predominantly in the DCT, connecting tubule, and cortical collecting duct, with lesser expression in the thick ascending limb of Henle and in the medullary collecting duct. Kir7.1 was detected by electron microscopic immunocytochemistry on the basolateral membrane of the DCT and the principal cells of cortical collecting duct, but neither type A nor type B intercalated cells were stained. The message levels and immunoreactivity were decreased under low-K diet and reversed by low-K diet supplemented with 4% KCl. By the double-labeling immunogold method, both Kir7.1 and Na + , K + -ATPase were independently located on the basolateral membrane. In conclusion, the novel Kir7.1 potassium channel is located predominantly in the basolateral membrane of the distal nephron and collecting duct where it could function together with Na + , K + -ATPase and contribute to cell ion homeostasis and tubular K + secretion.
Functional pain syndromes: presentation and pathophysiology
Authors: Q. Aziz, C. Botha
Journal: Gut (2010)

Edited by Emeran Mayer, M Catherine Bushnell. Published by International Association for the Study of Pain Press, Seattle, 2009, pp 580, £50 (softcover). ISBN-10: 0931092752 & ISBN-13: 978-0931092756.

An excellent book that will become essential reading for anybody wishing to have an integrated understanding of functional pain and its treatment. The growing number of books like this one, which recognise and link similar ‘functional’ problems together, are to be welcomed and supported. This book echoes …
Cardiac-Specific Ablation of the Na <sup>+</sup> -Ca <sup>2+</sup> Exchanger Confers Protection Against Ischemia/Reperfusion Injury
Authors: Kenichi Imahashi, Christian Pott, Joshua I. Goldhaber, Charles Steenbergen, Kenneth D. Philipson, Elizabeth Murphy
Journal: Circulation Research (2005)

During ischemia and reperfusion, with an increase in intracellular Na + and a depolarized membrane potential, Ca 2+ may enter the myocyte in exchange for intracellular Na + via reverse-mode Na + -Ca 2+ exchange (NCX). To test the role of Ca 2+ entry via NCX during ischemia and reperfusion, we studied mice with cardiac-specific ablation of NCX (NCX-KO) and demonstrated that reverse-mode Ca 2+ influx is absent in the NCX-KO myocytes. Langendorff perfused hearts were subjected to 20 minutes of global ischemia followed by 2 hours of reperfusion, during which time we monitored high-energy phosphates using 31 P-NMR and left-ventricular developed pressure. In another group of hearts, we monitored intracellular Na + using 23 Na-NMR. Consistent with Ca 2+ entry via NCX during ischemia, we found that hearts lacking NCX exhibited less of a decline in ATP during ischemia, delayed ischemic contracture, and reduced maximum contracture. Furthermore, on reperfusion following ischemia, NCX-KO hearts had much less necrosis, better recovery of left-ventricular developed pressure, improved phosphocreatine recovery, and reduced Na + overload. The improved recovery of function following ischemia in NCX-KO hearts was not attributable to the reduced preischemic contractility in NCX-KO hearts, because when the preischemic workload was matched by treatment with isoproterenol, NCX-KO hearts still exhibited improved postischemic function compared with wild-type hearts. Thus, NCX-KO hearts were significantly protected against ischemia-reperfusion injury, suggesting that Ca 2+ entry via reverse-mode NCX is a major cause of ischemia/reperfusion injury.
An unfortunate way to die
Authors: M. O'Donnell
Journal: BMJ (2010)

When I was writing the BBC Radio 4 series The Age Old Dilemma I talked to the relatives of old people who had died in hospital. I also sat in on medical discussions of “care of the dying” and was intrigued by the disparity between the way patients perceived events and the way doctors described the same events when they discussed them with their peers.

That disparity emerged in an article the BMJ published last November telling the story of a 62 year old woman “bed bound with severe arthritis and in constant pain despite strong opioid treatment” ( BMJ 2009;339:b4667, doi:10.1136/bmj.b4667). After writing an advanced directive and a detailed suicide note that “clearly expressed [her] distress at her longstanding pain and severe restriction of function and independence” she swallowed a potent concoction of sedatives and sank into what she assumed would be oblivion.

I can only guess at her assumption, because, as is traditional in our journals, her story is written by the doctors. We read in detail the arguments they considered and …
Dystrophin Immunity in Duchenne's Muscular Dystrophy
Authors: Jerry R. Mendell, Katherine Campbell, Louise Rodino-Klapac, Zarife Sahenk, Chris Shilling, Sarah Lewis, Dawn Bowles, Steven James Gray, Chengwen Li, Gloria Galloway, Vinod Malik, Brian Coley, K. Reed Clark, Juan Li, Xiao Xiao, Jade Samulski, Scott W. McPhee, R. Jude Samulski, Christopher M. Walker
Journal: New England Journal of Medicine (2010)

We report on delivery of a functional dystrophin transgene to skeletal muscle in six patients with Duchenne's muscular dystrophy. Dystrophin-specific T cells were detected after treatment, providing evidence of transgene expression even when the functional protein was not visualized in skeletal muscle. Circulating dystrophin-specific T cells were unexpectedly detected in two patients before vector treatment. Revertant dystrophin fibers, which expressed functional, truncated dystrophin from the deleted endogenous gene after spontaneous in-frame splicing, contained epitopes targeted by the autoreactive T cells. The potential for T-cell immunity to self and nonself dystrophin epitopes should be considered in designing and monitoring experimental therapies for this disease. (Funded by the Muscular Dystrophy Association and others; ClinicalTrials.gov number, NCT00428935.).
Darbepoetin‐alfa and intravenous iron administration after autologous hematopoietic stem cell transplantation: A prospective multicenter randomized trial
Authors: Yves Beguin, Johan Maertens, Bernard De Prijck, Rik Schots, Laurence Seidel, Christophe Bonnet, Kaoutar Hafraoui, Evelyne Willems, Gaetan Vanstraelen, Sophie Servais, Aurélie Jaspers, Georges Fillet, Frederic Baron
Journal: American Journal of Hematology (2013)

We conducted a randomized study analyzing the impact of darbepoetin alfa (DA) administration with or without intravenous (i.v.) iron on erythroid recovery after autologous hematopoietic cell transplantation (HCT). Patients were randomized between no DA (Arm 1), DA 300 μg every 2 weeks starting on Day 28 after HCT (Arm 2), or DA plus i.v. iron 200 mg on Days 28, 42, and 56 (Arm 3). The proportion achieving complete hemoglobin (Hb) response within 18 weeks (primary end point) was 21% in Arm 1 ( n = 24), 79% in Arm 2 ( n = 25), and 100% in Arm 3 ( n = 23; P &lt; 0.0001). Erythropoietic response was shown to be significantly higher in Arm 3 ( n = 46) than in Arm 2 ( n = 50; P = 0.008), resulting in lower DA use, reduced drug costs, and improved quality of life scores, but the effect on transfusions was not significant. In multivariate analysis, DA administration ( P &lt; 0.0001), i.v. iron administration ( P = 0.0010), high baseline Hb ( P &lt; 0.0001), and low baseline creatinine ( P = 0.0458) were independently associated with faster achievement of complete Hb response. In conclusion, DA is highly effective to ensure full erythroid reconstitution after autologous HCT when started on Day 28 post‐transplant. I.v. iron sucrose further improves erythroid recovery. Am. J. Hematol. 88:990–996, 2013. © 2013 Wiley Periodicals, Inc.
Cognitive behavioural model of irritable bowel syndrome
Authors: F. Creed
Journal: Gut (2007)

<h3>Objectives:</h3> We examined the relationship between self-rated health and incident dementia, and investigated the impact of cognitive complaints, depressive symptoms, and functional status on this relationship. <h3>Methods:</h3> Participants of the 3C Study, a prospective cohort study composed of 8,169 community-dwelling persons aged ≥65 years, were asked to rate their health at the baseline examination in 1999–2001. They were followed for a median of 6.7 years during which dementia was screened and diagnosed. Hazard ratios (HR) of dementia according to baseline self-rated health (good, fair, or poor) were estimated with a Cox model adjusted for potential confounders. <h3>Results:</h3> During the 46,990 person-years of follow-up, 618 participants developed dementia. Risk of dementia was increased in participants with poor (adjusted HR 1.70, 95% confidence interval [CI] 1.22–2.37) or fair (adjusted HR 1.34, 95% CI 1.13–1.59) self-rated health compared to those with good self-rated health. Poor self-rated health was associated with both AD (1.48, 1.00–2.24) and vascular dementia (3.38, 1.25–9.17). Self-rated health was a stronger predictor of dementia in participants without cognitive complaints (risk of dementia in subjects without cognitive complaints rating their health as poor: 1.96 [1.24–3.09], <i>p</i> = 0.004) and in those without functional disability. <h3>Conclusions:</h3> Participants rating their health as poor or fair at baseline were at increased risk of incident dementia during follow-up. Self-rated health could help raise awareness of medical doctors about a patient9s risk of dementia, especially in those without conditions indicative of potential cognitive impairment.
Critical Role of Cyclin D1 Nuclear Import in Cardiomyocyte Proliferation
Authors: Mimi Tamamori-Adachi, Hiroshi Ito, Piyamas Sumrejkanchanakij, Susumu Adachi, Michiaki Hiroe, Masato Shimizu, Junya Kawauchi, Makoto Sunamori, Fumiaki Marumo, Shigetaka Kitajima, Masa-Aki Ikeda
Journal: Circulation Research (2003)

Mammalian cardiomyocytes irreversibly lose their capacity to proliferate soon after birth, yet the underlying mechanisms have been unclear. Cyclin D1 and its partner, cyclin-dependent kinase 4 (CDK4), are important for promoting the G1-to-S phase progression via phosphorylation of the retinoblastoma (Rb) protein. Mitogenic stimulation induces hypertrophic cell growth and upregulates expression of cyclin D1 in postmitotic cardiomyocytes. In the present study, we show that, in neonatal rat cardiomyocytes, D-type cyclins and CDK4 were predominantly cytoplasmic, whereas Rb remained in an underphosphorylated state. Ectopically expressed cyclin D1 localized in the nucleus of fetal but not neonatal cardiomyocytes. To target cyclin D1 to the nucleus efficiently, we constructed a variant of cyclin D1 (D1NLS), which directly linked to nuclear localization signals (NLSs). Coinfection of recombinant adenoviruses expressing D1NLS and CDK4 induced Rb phosphorylation and CDK2 kinase activity. Furthermore, D1NLS/CDK4 was sufficient to promote the reentry into the cell cycle, leading to cell division. The number of cardiomyocytes coinfected with these viruses increased 3-fold 5 days after infection. Finally, D1NLS/CDK4 promoted cell cycle reentry of cardiomyocytes in adult hearts injected with these viruses, evaluated by the expression of Ki-67, which is expressed in proliferating cells in all phases of the cell cycle, and BrdU incorporation. Thus, postmitotic cardiomyocytes have the potential to proliferate provided that cyclin D1/CDK4 accumulate in the nucleus, and the prevention of their nuclear import plays a critical role as a physical barrier to prevent cardiomyocyte proliferation. Our results provide new insights into the development of therapeutics strategies to induce regeneration of cardiomyocytes. The full text of this article is available at http://www.circresaha.org.
Identification in situ of T lymphocytes in the dermal and epidermal infiltrates of mycosis fungoides
Authors: A.C. CHU, D.M. MACDONALD
Journal: British Journal of Dermatology (1979)

Frozen tissue sections from the lesions of five patients with histologically proven mycosis fungoides were examined using a specific antihuman T-cell antiserum and an indirect peroxidase staining technique. The dermal and epidermal infiltrates were shown to comprise predominantly cells bearing the specific T-cell antigen, HTLA. Two of the patients exhibited characteristic Pautrier microabscesses whose cells were exclusively T lymphocytes.
Lessons Learned in the Management of Advanced Pancreatic Cancer
Authors: Eric Van Cutsem, Chris Verslype, Patrick A. Grusenmeyer
Journal: Journal of Clinical Oncology (2007)

The treatment of patients with advanced pancreatic cancer remains a major challenge. The outcome for this condition is extremely poor, with the median survival of patients treated with best supportive care within approximately 3 to 4 months. Patients treated with gemcitabine have a median survival of approximately 6 months and a 1-year survival rate of approximately 20%. Gemcitabine has been widely accepted as the standard treatment based on a relatively small study showing a modest, but statistically significant, improvement in overall survival as well as improved clinicalbenefitcomparedwithbolusfluorouracilplusleucovorin. 1 Although a pharmacokinetic rationale exists for administering gemcitabineoveraprolongedinfusedover150minutes(fixeddose rate [FDR]), with a small clinical study suggesting high activity, a randomized phase III study comparing the FDR regimen and the standard 30-minute infusion failed to show superiority for FDR gemcitabine. 2,3 Gemcitabine has been combined with a variety of cytotoxic agents and targeted agents (Tables 1, 2, and 3). 3-17 Most phase III studies, however, have failed to show improved survival comparedwithgemcitabinealone. 3-8 OnephaseIIIstudycomparingthecombinationofgemcitabineandcapecitabinewithgemcitabine monotherapy has shown a significantly improved median and 1-year survival in favor of the combination arm: 7.4 months versus 6.0 months and 26% versus 19%, respectively, with a favorable safety profile. 9 This study of 533 patients used a different regimen of gemcitabine plus capecitabine than a smaller study, in 319 patients that showed a trend, but no significant difference, compared with gemcitabine monotherapy. 9,10 This latter study was underpowered to show a survival difference. Other studies with gemcitabine, with or without intravenous fluorouracil all failed to show a difference between gemcitabine monotherapy and combination treatment. 11-13
The role of the sports and exercise medicine physician in the National Health Service: a questionnaire-based survey
Authors: P O’Halloran, V Tzortziou Brown, K Morgan, N Maffulli, M Perry, D Morrissey
Journal: British Journal of Sports Medicine (2009)

To investigate the opinions of general practitioners, orthopaedic surgeons, rheumatologists, sport and exercise medicine (SEM) registrars and public health consultants on training, caseload, the most appropriate setting and the position of SEM within the National Health Service (NHS) in the UK.A cross-sectional questionnaire-based survey investigated the opinions of the above professionals from three primary care trusts and associated hospitals in London and Birmingham.With a 50% response rate (n = 226), 93% (208/224) of participants felt that there was a role for SEM in the NHS. 56% (124/223) agreed that this role should be in both primary and secondary care. 64% (136/212) of participants felt that their practice would benefit from the input of a SEM physician and 95% (191/202) would consider referring patients to SEM services. 74% (165/222) agreed that SEM should have a public health role, and 63% (140/222) believed that these responsibilities should be evenly balanced with the treatment of sports injuries. Despite the emphasis on public health work from SEM policy makers, none of the SEM registrars selected public health as an important training area. 31% (44/140) of participants felt that a lack of education in the medical profession regarding SEM represented the greatest hindrance to its development in the NHS.Several areas of agreement were demonstrated across the specialties, many of which matched the views of policy makers. This study involved participants from a range of cognate disciplines and was the first to investigate this issue since SEM was recognised as a specialty in 2005.
Detection of <i>miR-34a</i> Promoter Methylation in Combination with Elevated Expression of c-Met and β-Catenin Predicts Distant Metastasis of Colon Cancer
Authors: Helge Siemens, Jens Neumann, Rene Jackstadt, Ulrich Mansmann, David Horst, Thomas Kirchner, Heiko Hermeking
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Here, we determined whether epigenetic inactivation of miR-34a and miR-34b/c genes may serve as a prognostic marker for distant metastases in colon cancer. Experimental Design: Using a case–control study design of 94 primary colon cancer samples with and without liver metastases, we determined CpG methylation frequencies of miR-34a and miR-34b/c promoters, expression of miR-34a, and its targets c-Met, Snail, and β-catenin and their prognostic value. Results: miR-34a methylation was detected in 45.1% (n = 42 of 93) of the samples and strongly associated with metastases to the liver (P = 0.003) and lymph nodes (P = 0.006). miR-34b/c methylation was detected in 91.9% of the samples (n = 79/86). A significant inverse correlation between miR-34a methylation and expression of mature miR-34a (P = 0.018) was detected. Decreased miR-34a expression was associated with upregulation of c-Met, Snail, and β-catenin protein levels (P = 0.031, 0.132, and 0.004), which were associated with distant metastases (P = 0.001, 0.017, and 0.005). In a confounder-adjusted multivariate regression model miR-34a methylation, high c-Met and β-catenin levels provided the most significant prognostic information about metastases to the liver (P = 0.014, 0.031, and 0.058) and matched pairs showed a higher prevalence of these risk factors in the samples with distant spread (P = 0.029). Finally, we obtained statistical evidence indicating that the simultaneous detection of these three markers has the highest prognostic value. Conclusions: Silencing of miR-34a and upregulation of c-Met, Snail, and β-catenin expression is associated with liver metastases of colon cancer. Detection of miR-34a silencing in resected primary colon cancer may be of prognostic value, especially in combination with detection of c-Met and β-catenin expression. Clin Cancer Res; 19(3); 710–20. ©2012 AACR.
Hepatic Gluconeogenesis/Glycolysis: Regulation and Structure/Function Relationships of Substrate Cycle Enzymes
Authors: S J Pilkis, T H Claus
Journal: Annual Review of Nutrition (1991)

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved ...Read More
Lifetime Risk of ESRD
Authors: Tanvir Chowdhury Turin, Marcello Tonelli, Braden J. Manns, Sofia B. Ahmed, Pietro Ravani, Matthew James, Brenda R. Hemmelgarn
Journal: Journal of the American Society of Nephrology (2012)

Lifetime risk is the cumulative risk of experiencing an outcome between a disease-free index age and death. The lifetime risk of ESRD for a middle-aged individual is a relevant and easy to communicate measure of disease burden. We estimated lifetime risk of ESRD in a cohort of 2,895,521 adults without ESRD from 1997 to 2008. To estimate lifetime risk of ESRD by level of baseline kidney function, we analyzed a cohort of participants who had a serum creatinine measurement. We also estimated the sex- and index age-specific lifetime risk of incident ESRD and accounted for the competing risk of death. Among those individuals without ESRD at age 40 years, the lifetime risk of ESRD was 2.66% for men and 1.76% for women. The risk was higher in persons with reduced kidney function: for eGFR=44-59 ml/min per 1.73 m(2), the lifetime risk of ESRD was 7.51% for men and 3.21% for women, whereas men and women with relatively preserved kidney function (eGFR=60-89 ml/min per 1.73 m(2)) had lifetime risks of ESRD of 1.01% and 0.63%, respectively. The lifetime risk of ESRD was consistently higher for men at all ages and eGFR strata compared with women. In conclusion, approximately 1 in 40 men and 1 in 60 women of middle age will develop ESRD during their lifetimes (living into their 90s). These population-based estimates may assist individuals who make decisions regarding public health policy.