tbuckley/cabot-search huggingface dataset:
Poor Glycemic Control Is a Major Factor in the Overestimation of Glomerular Filtration Rate in Diabetic Patients
Authors: Akihiro Tsuda, Eiji Ishimura, Yoshiteru Ohno, Mitsuru Ichii, Shinya Nakatani, Yuuichi Machida, Katsuhito Mori, Junji Uchida, Shinya Fukumoto, Masanori Emoto, Tatsuya Nakatani, Masaaki Inaba
Journal: Diabetes Care (2013)

OBJECTIVE Serum creatinine levels are lower in diabetic patients compared with their nondiabetic counterparts. Therefore, estimated glomerular filtration rate (eGFR) is higher in the former than in the latter group. Factors associated with overestimation of renal function in diabetic patients were examined, and new formulae reflecting precise eGFR were created. RESEARCH DESIGN AND METHODS Eighty subjects (age 56.5 ± 15.4 years; 35 males [43.8%]; 40 patients with diabetes and 40 nondiabetic subjects) were enrolled. GFR was evaluated by inulin clearance (Cin). eGFR values were calculated based on serum creatinine and/or serum cystatin C levels. The factors related to the dissociation between eGFR and Cin in diabetic patients and the agreement among each of three eGFR and Cin were compared. RESULTS Although Cin was not significantly different between the diabetic and nondiabetic subjects (P = 0.2866), each of three eGFR measures from the diabetic patients was significantly higher than that of the nondiabetic subjects (P < 0.01). There were significant and positive correlations between the ratio of each eGFR/Cin, hemoglobin A1c, and glycated albumin. The intraclass correlation coefficients in diabetic patients were weaker than those in the nondiabetic subjects, and the intercepts of the regression lines between each eGFR measure and Cin in the diabetic patients were significantly higher than those of the nondiabetic subjects. New formulae for the calculation of eGFR corrected by the glycemic control indices were better than the original eGFR, particularly in diabetic patients. CONCLUSIONS eGFR overestimates Cin as glycemic controls worsen. eGFR corrected by hemoglobin A1c is considered to be clinically useful and feasible.
Phase II Clinical Trial Results Involving Treatment with Low-Dose Daily Oral Cyclophosphamide, Weekly Vinblastine, and Rofecoxib in Patients with Advanced Solid Tumors
Authors: Scott D. Young, Mark Whissell, Jonathan C.S. Noble, Pablo O. Cano, Pedro G. Lopez, Colin J. Germond
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Preclinical studies indicate that conventional chemotherapeutic agents given continuously at low doses (metronomic chemotherapy) may provide an improved therapeutic index. Cyclophosphamide and vinblastine have been best studied in experimental models, where tumor growth inhibition is achieved, at least in part, through antiangiogenic mechanisms. Experimental Design: Fifty patients with advanced solid tumors were enrolled in this phase II trial, 43 of whom had received at least one prior chemotherapy regimen. Patients were required to have Eastern Cooperative Oncology Group performance status of ≤2, a life expectancy of &amp;gt;3 months, and at least one measurable lesion. All patients received oral cyclophosphamide (50 mg) and rofecoxib (25 mg) daily in addition to weekly injections of vinblastine (3 mg/m2). Half of the patients also received minocycline (100 mg) orally twice daily with the intent of further inhibiting tumor angiogenesis. The primary end point of the study was clinical benefit, defined as the percentage of patients experiencing an objective response or exhibiting stable disease for at least 6 months. Results: For the 47 eligible patients, there were two (4%) complete responses and four (9%) partial responses, for an overall objective response rate of 13%. An additional eight patients achieved disease stabilization (stable disease ≥6 months) (17%). The primary end point of clinical benefit was therefore 30%, (95% confidence interval, 16-44%). The median progression-free survival for all patients was 103 days and 289 days for patients experiencing clinical benefit. The incidence of patients experiencing grade 3/4 toxicities were as follows: neutropenia (10/2), anemia (2/0), and thrombocytopenia (1/0). No patients developed grade 3 or 4 nausea, vomiting, mucositis, or alopecia. Conclusions: This low-dose regimen consisting of daily oral cyclophosphamide and weekly vinblastine injections given concurrently with rofecoxib is associated with minimal toxicity and provides significant clinical benefit to patients with advanced solid tumors. These results are particularly encouraging given the nature of the study population and indicate that this approach merits further investigation in specific disease site studies.
Splicing-Directed Therapy in a New Mouse Model of Human Accelerated Aging
Authors: Fernando G. Osorio, Claire L. Navarro, Juan Cadiñanos, Isabel C. López-Mejía, Pedro M. Quirós, Catherine Bartoli, José Rivera, Jamal Tazi, Gabriela Guzmán, Ignacio Varela, Danielle Depetris, Félix de Carlos, Juan Cobo, Vicente Andrés, Annachiara De Sandre-Giovannoli, José M. P. Freije, Nicolas Lévy, Carlos López-Otín
Journal: Science Translational Medicine (2011)

Hutchinson-Gilford progeria syndrome (HGPS) is caused by a point mutation in the LMNA gene that activates a cryptic donor splice site and yields a truncated form of prelamin A called progerin. Small amounts of progerin are also produced during normal aging. Studies with mouse models of HGPS have allowed the recent development of the first therapeutic approaches for this disease. However, none of these earlier works have addressed the aberrant and pathogenic LMNA splicing observed in HGPS patients because of the lack of an appropriate mouse model. Here, we report a genetically modified mouse strain that carries the HGPS mutation. These mice accumulate progerin, present histological and transcriptional alterations characteristic of progeroid models, and phenocopy the main clinical manifestations of human HGPS, including shortened life span and bone and cardiovascular aberrations. Using this animal model, we have developed an antisense morpholino-based therapy that prevents the pathogenic Lmna splicing, markedly reducing the accumulation of progerin and its associated nuclear defects. Treatment of mutant mice with these morpholinos led to a marked amelioration of their progeroid phenotype and substantially extended their life span, supporting the effectiveness of antisense oligonucleotide-based therapies for treating human diseases of accelerated aging.
Grannloma annulare and sarcoidosis
Authors: E.L. Rhodes
Journal: British Journal of Dermatology (1979)

Journal Article Grannloma annulare and sarcoidosis Get access E.L. Rhodes E.L. Rhodes Dermatology Department, St Helier Hospital, Carshalton, Surrey Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 100, Issue 2, 1 February 1979, Page 231, https://doi.org/10.1111/j.1365-2133.1979.tb05570.x Published: 01 February 1979
Rectal epithelial apoptosis in familial adenomatous polyposis patients treated with sulindac
Authors: J J Keller, G J A Offerhaus, M Polak, S N Goodman, M L Zahurak, L M Hylind, S R Hamilton, F M Giardiello
Journal: Gut (1999)

<h3>BACKGROUND</h3> Sulindac regresses colorectal adenomas in patients with familial adenomatous polyposis (FAP), although the mechanism of polyp regression is unclear. <h3>AIMS</h3> To determine whether differences occur in alteration of rectal epithelial apoptotic index and expression of apoptosis related proteins in FAP patients treated with sulindac compared with placebo. <h3>PATIENTS</h3> Twenty one FAP patients; 12 had not undergone colectomy. <h3>METHODS</h3> Patients with FAP were treated with sulindac 150 mg orally twice a day for three months (n=10) or placebo (n=11). Colorectal polyp number was determined and biopsies of the normal rectal mucosa were performed before and after three months of treatment. Response to treatment and alteration of the apoptotic ratio (index in base of crypt divided by index in surface epithelium) were evaluated. Bcl-2, bax, p21/WAF-1, and p53 proteins were assessed semiquantitatively by immunohistochemistry. <h3>RESULTS</h3> Significant decreases in polyp number and in the apoptotic ratio were seen in patients treated with sulindac compared with controls. The mean percentage change in polyp number from baseline was −46% in the sulindac group and +13% in the placebo group (p=0.005). Mean percentage change in the apoptotic ratio was −8% and +25% in the sulindac and placebo treated patients, respectively (p=0.004). No differences in expression or compartmentalisation of apoptosis related proteins were noted between treatment groups. <h3>CONCLUSIONS</h3> Sulindac regression of colorectal adenomas is accompanied by alteration of the rectal epithelial apoptotic ratio with relative increase in apoptosis in surface cells compared with the deeper crypt. The utility of the apoptotic ratio as an intermediate biomarker for colorectal tumorigenesis deserves further study.
Quantifying Diet for Nutrigenomic Studies
Authors: Katherine L. Tucker, Caren E. Smith, Chao-Qiang Lai, Jose M. Ordovas
Journal: Annual Review of Nutrition (2013)

The field of nutrigenomics shows tremendous promise for improved understanding of the effects of dietary intake on health. The knowledge that metabolic pathways may be altered in individuals with genetic variants in the presence of certain dietary exposures offers great potential for personalized nutrition advice. However, although considerable resources have gone into improving technology for measurement of the genome and biological systems, dietary intake assessment remains inadequate. Each of the methods currently used has limitations that may be exaggerated in the context of gene × nutrient interaction in large multiethnic studies. Because of the specificity of most gene × nutrient interactions, valid data are needed for nutrient intakes at the individual level. Most statistical adjustment efforts are designed to improve estimates of nutrient intake distributions in populations and are unlikely to solve this problem. An improved method of direct measurement of individual usual dietary intake that is unbiased across populations is urgently needed.
1131-146 Serial echocardiographic follow-up of percutaneous left atrial appendage transcatheter occlusion (PLAATO TM ) in patients with atrial fibrillation
Authors: Athena Poppas, Toshiko Nakai, Horst Sievert, Linda Crouse, Bruce L Macrum, Kimberly Krabill, Sandra Gan, Randolph Martin, Heyder Omran, Mauro Pepi, Fabio Sgura, Christian Seller, Linda Clarke, Richard Kutnick, David Rubenson, Bryan Dias, Mark Reisman
Journal: Journal of the American College of Cardiology (2004)
Angiopoietin-1 is expressed in the synovium of patients with rheumatoid arthritis and is induced by tumour necrosis factor alpha
Authors: E M Gravallese
Journal: Annals of the Rheumatic Diseases (2003)

<h3>Introduction</h3> Herpes simplex labialis (HSL) is a common infection that can cause painful lesions on the oral mucosa, commonly referred to as cold sores. Current biomedical treatments include topical aciclovir, which reduces the episode duration by an average of 0.5 days. This study will examine the efficacy and tolerability of an over-the-counter topical treatment, Dynamiclear in reducing duration and severity of HSL episodes. <h3>Methods and analysis</h3> This prospective, randomised, double-blind, placebo-controlled, multi-centre trial will recruit a minimum of 292 adult participants across Australia and New Zealand who present with a cold sore within 48 hours of onset. They will be randomly allocated in a 2:1 ratio to receive either topical Dynamiclear (active) or placebo. Dynamiclear's active ingredients are <i>Hypericum perforatum</i>, <i>Calendula Officinalis</i> and copper sulfate. A single topical treatment of active or placebo will be applied by a pharmacy-based investigator, and participants will be provided with a viral swab kit to confirm presence of herpes virus 1 or 2 from ulcerated lesions. Participants will receive reminders by email and/or SMS to complete an online daily diary assessing their cold sore lesion using a visual guide, and recording other symptoms on numeric scales until healed. The primary outcome variable is median duration of HSL episode in days (participant evaluated) from presentation to return to normal skin. Secondary outcomes include severity of lesion pain, itching, burning and tingling during the symptomatic phase and proportion of lesions progressing to ulceration. <h3>Ethics and dissemination</h3> Australian ethics approval from Western Sydney University Human Research Ethics Committee, ref: H12776. New Zealand Ethics approval from The Health and Disability Ethics Committees (HDEC) ref: 18/CEN/151. Results will be published in a peer-reviewed academic journal, presented at academic meetings and reported to participants <h3>Trial registration numbers</h3> Australia and New Zealand Clinical Trials Registry (ACTRN12618000890235); Universal Trial Number (UTN) (U1111-1233-2426).
Foreign Certification in Psychiatry
Authors: JAMES M.A. WEISS
Journal: American Journal of Psychiatry (1971)

The author's survey of psychiatry department chairmen in the United States disclosed that a large majority regard certification in psychiatry by the Royal Colleges of Physicians and Surgeons of Canada and England as roughly equivalent to certification by the ABPN in psychiatry; they do not, however, regard certification by other foreign agencies as equivalent.
Safety and Tolerance of Oral Rehydration Solution (ORS) for Cisplatin-Based Chemotherapy in Patients with Lung Cancer
Authors: T. Yokoyama, S. Takata, I. Hirukawa, T. Inui, K. Yano, R. Seki, H. Wada, S. Nagai, H. Takizawa, H. Goto
Journal: Annals of Oncology (2013)
A Conversation with Paul Greengard
Authors: Paul Greengard, Eric J. Nestler
Journal: The Annual Review of Pharmacology and Toxicology (2013)

Introduction Paul Greengard was born in New York City in 1925. After completing high school, he served three years in the US Navy during World War II and then completed his bachelor's degree at Hamilton College where he majored in physics and mathematics. He obtained a PhD in biophysics from Johns Hopkins University in 1953 and pursued postdoctoral training with Wilhelm Feldberg at the National Institute for Medical Research in England. After eight years as head of biochemistry at Geigy, and sabbaticals at Albert Einstein College of Medicine and Vanderbilt University, he joined the Yale University faculty as a full professor of pharmacology in 1968. While he was at Yale, Greengard's laboratory performed groundbreaking research, which demonstrated a role for cyclic nucleotides, protein kinases and protein phosphatases, and their protein substrates in the regulation of synaptic transmission. In 1983, Greengard moved to The Rockefeller University, where he has since served as the Vincent Astor Professor and Head of the Laboratory of Molecular and Cellular Neuroscience. Greengard's paradigm-shifting research has continued at Rockefeller and has informed our understanding and possible treatment of a host of brain disorders, including schizophrenia, Alzheimer's disease, Parkinson's disease, and depression. He is the author of more than 950 research articles and reviews. Greengard has received numerous awards and honors, including the Nobel Prize in Physiology or Medicine in 2000, the Metropolitan Life Foundation Award for Medical Research, The National Academy of Sciences Award in Neuroscience, the Ralph W. Gerard Prize in Neuroscience for the Society for Neuroscience, and the Karolinska Institutet's Bicentennial Gold Medal. He is a member of the US National Academy of Sciences and the Institute of Medicine of the National Academies. The following interview was conducted on May 29, 2012.
Distilling Cancer Biomarkers From the Serum Peptidome: High Technology Reading of Tea Leaves or an Insight to Clinical Systems Biology?
Authors: Richard J. Robbins, Josep Villanueva, Paul Tempst
Journal: Journal of Clinical Oncology (2005)

Inthisissue,Mianetal 1 usehigh-resolutionmassspectrometry (MS) to define the serum peptidome of patients with melanoma. They trained machine learning algorithms to recognize serum peptidomic patterns that clustered with specific disease states. This strategy enabled them to discriminatestageImelanomapatientsfromstageIVpatients. Furthermore,thepeptidomicpatternswereabletodiscriminate stage III melanoma patients who developed tumor recurrences within the first year after diagnosis from stage III patients who remained disease free. An artificial neural network analysis of the peptide patterns was able to correctly identify 80% of patients who eventually experienced recurrence,comparedwitha21%predictionratewhentheseinves
Anti-inflammatory effects of adiponectin in A549 cells exposed to TNFα and IL-1β
Authors: Ersilia Nigro, Olga Scudiero, Daniela Sarnataro, Maria Ludovica Monaco, Nicolina De Rosa, Matteo Sofia, Andrea Bianco, Aurora Daniele
Journal: European Respiratory Journal (2012)

Adiponectin (Acrp30) is an insulin-sensitizing hormone with beneficial effects on a number of biological and metabolic processes by two widely expressed receptors, AdipoR1 and AdipoR2. To date, the role of Acrp30 in lung is not completely assessed but altered levels of Acrp30 and modulated expression of both AdipoRs have been described in Chronic Obstructive Pulmonary disease (COPD) (1). Lung inflammation, a crucial component of COPD progression, is mainly sustained by two potent pro-inflammatory cytokines: Tumor Necrosis Factor α (TNFα) and Interleukin 1β (IL-1β). These mediators in turn propagate and perpetuate the inflammation also through NF-κB, a transcriptional factor for many genes involved in inflammation, injury and stress in lung. In this study we analyzed the effects of Acrp30 on human alveolar epithelial cell line (A549) selected as an in vitro model of lung epithelia. We treated A549 cells with TNFα or IL-1β and visualized the NF-κB nuclear transactivation by confocal microscopy. Successively, we evaluated the role of Acrp30 in this process: we treated the cells with Acrp30 and subsequently with TNFα or IL-1β and analyzed NF-κB nuclear transactivation. Finally, we investigated by western blotting the phosphorylation status of ERK1/2 kinase, one of the main molecules involved in Acrp30 signal pathway. A better elucidation of the Acrp30 role in the control of local lung inflammatory state may contribute to develop new therapeutic approaches in inflammatory diseases as COPD, a major cause of morbidity and death worldwide.  Acknowledgment: PRIN 2007; Regione Campania, DGRC 1901/2009  1Daniele A et al. Int J Biochem Cell Biol. 2012 Mar;44(3):563-9.
Immunochemotherapy with rituximab, methotrexate, procarbazine, and lomustine for primary CNS lymphoma (PCNSL) in the elderly
Authors: K. Fritsch, B. Kasenda, C. Hader, G. Nikkhah, M. Prinz, V. Haug, S. Haug, G. Ihorst, J. Finke, G. Illerhaus
Journal: Annals of Oncology (2011)
Phagocytosis of Histoplasma capsulatum yeasts and microconidia by human cultured macrophages and alveolar macrophages. Cellular cytoskeleton requirement for attachment and ingestion.
Authors: S L Newman, C Bucher, J Rhodes, W E Bullock
Journal: Journal of Clinical Investigation (1990)

Phagocytosis of Histoplasma capsulatum (Hc) yeasts and microconidia by human macrophages (M phi) was quantified by a fluorescence quenching technique. Phagocytosis of unopsonized Hc yeasts by monocyte-derived M phi and human alveolar M phi (AM) was rapid. After 60 min, 79% of cultured M phi and 59% of AM had ingested an average of 9.8 and 11 yeasts/M phi, respectively. In contrast, only 26% of monocytes ingested 4.5 yeasts/cell after 60 min. Phagocytosis of unopsonized microconidia by cultured M phi and by AM was equivalent. Monoclonal antibodies specific for the alpha-chains and beta-chain of the CD18 family of adhesion receptors inhibited the binding of Hc yeasts and microconidia to cultured M phi and AM. Thus, the M phi CD18 complex mediates recognition of both phases of this dimorphic fungus. Disruption of actin microfilaments with cytochalasin D inhibited both attachment and ingestion of yeasts by M phi. In contrast, nocodazole, which prevents polymerization of microtubules, did not inhibit binding or ingestion. Both drugs inhibited ingestion, but neither drug inhibited binding of C3b- and C3bi-coated sheep erythrocytes to complement receptors type one (CR1) or type three (CR3), respectively. Therefore, different signal transducing mechanisms for phagocytosis appear to be triggered by the binding of Hc yeasts to CD18, and by the binding of EC3bi to CD11b/CD18, respectively.
Two closely linked variations in actin cytoskeleton pathway in a Chinese pedigree with disseminated superficial actinic porokeratosis
Authors: Zheng-Hua Zhang, Wei Huang, Zhen-Min Niu, Wei-Da Liu, Lei-Hong Xiang, Wen-Tao Yuan, Jing-Jun Zhao, Chao-Ying Gu, Bao Chai, Fa-Xing Jiang, Jing Zhang, Shi-Jie Xu, Zhi-Zhong Zheng
Journal: Journal of the American Academy of Dermatology (2005)
Erlotinib for Advanced Non–Small-Cell Lung Cancer in the Elderly: An Analysis of the National Cancer Institute of Canada Clinical Trials Group Study BR.21
Authors: Paul Wheatley-Price, Keyue Ding, Lesley Seymour, Gary M. Clark, Frances A. Shepherd
Journal: Journal of Clinical Oncology (2008)

Purpose National Cancer Institute of Canada Clinical Trials Group Study BR.21 established erlotinib as a standard of care in patients with non–small-cell lung cancer (NSCLC) after failure of first- or second-line chemotherapy. The current study analyzes the influence of age on outcomes in BR.21. Patients and Methods BR.21 was a double-blind phase III trial that randomly assigned 731 patients to erlotinib 150 mg daily or placebo. End points included progression-free survival and overall survival (OS), response, quality of life (QOL), drug exposure, and toxicity, which are analyzed in this retrospective study by the following two age groups: ≥ 70 years (elderly) or less than 70 years (young). Results There were 163 elderly patients (112 on erlotinib, 51 on placebo) and 568 young patients (376 on erlotinib, 192 on placebo). There was no significant difference between age groups randomly assigned to erlotinib or placebo in progression-free survival (elderly: 3.0 v 2.1 months; hazard ratio [HR] = 0.63; 95% CI, 0.44 to 0.90; P = .009; young: 2.1 v 1.8 months; HR = 0.64; 95% CI, 0.53 to 0.76; P &lt; .0001; interaction, P = .77) or OS (elderly: 7.6 v 5.0 months; HR = 0.92; 95% CI, 0.64 to 1.34; P = .67; young: 6.4 v 4.7 months; HR = 0.73; 95% CI, 0.61 to 0.89; P = .0014; interaction, P = .31). Response rates were similar between age groups. Elderly patients, compared with young patients, had significantly more overall and severe (grade 3 and 4) toxicity (35% v 18%; P &lt; .001), were more likely to discontinue treatment as a result of treatment-related toxicity (12% v 3%; P &lt; .0001), and had lower relative dose-intensity (64% v 82% received &gt; 90% planned dose; P &lt; .001). Conclusion Elderly patients treated with erlotinib gain similar survival and QOL benefits as younger patients but experience greater toxicity.
Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial
Authors: Michael P Manns, John G McHutchison, Stuart C Gordon, Vinod K Rustgi, Mitchell Shiffman, Robert Reindollar, Zachary D Goodman, Kenneth Koury, Mei-Hsiu Ling, Janice K Albrecht
Journal: The Lancet (2001)