tbuckley/cabot-search huggingface dataset:
Bevacizumab for neovascular age related macular degeneration (ABC Trial): multicentre randomised double masked study
Authors: A. Tufail, P. J. Patel, C. Egan, P. Hykin, L. da Cruz, Z. Gregor, J. Dowler, M. A. Majid, C. Bailey, Q. Mohamed, R. Johnston, C. Bunce, W. Xing
Journal: BMJ (2010)

<b>Objectives</b> To evaluate the efficacy and safety of intravitreous bevacizumab injections for the treatment of neovascular age related macular degeneration. <b>Design</b> Prospective, double masked, multicentre, randomised controlled trial. <b>Setting</b> Three ophthalmology centres in the United Kingdom. <b>Participants</b> 131 patients (mean age 81) with wet age related macular degeneration randomised 1:1 to intervention or control. <b>Interventions</b> Intravitreous bevacizumab (1.25 mg, three loading injections at six week intervals followed by further treatment if required at six week intervals) or standard treatment available at the start of the trial (photodynamic treatment with verteporfin for predominantly classic type neovascular age related macular degeneration, or intravitreal pegaptanib or sham treatment for occult or minimally classic type neovascular age related macular degeneration). <b>Main outcome measures</b> Primary outcome: proportion of patients gaining ≥15 letters of visual acuity at one year (54 weeks). Secondary outcomes: proportion of patients with stable vision and mean change in visual acuity. <b>Results</b> Of the 131 patients enrolled in the trial, five patients did not complete the study because of adverse events, loss to follow-up, or death. In the bevacizumab group, 21 (32%) patients gained 15 or more letters from baseline visual acuity compared with two (3%) in the standard care group (P&lt;0.001); the estimated adjusted odds ratio was 18.1 (95% confidence interval 3.6 to 91.2) and the number needed to treat was 4 (3 to 6). In addition, the proportion of patients who lost fewer than 15 letters of visual acuity from baseline was significantly greater among those receiving bevacizumab treatment (91% (59) <i>v</i> 67% (44) in standard care group; P&lt;0.001). Mean visual acuity increased by 7.0 letters in the bevacizumab group with a median of seven injections compared with a decrease of 9.4 letters in the standard care group (P&lt;0.001), and the initial improvement at week 18 (plus 6.6 letters) was sustained to week 54. Among 65 patients treated with bevacizumab, there were no cases of endophthalmitis or serious uveitis related to the intervention. All end points with respect to visual acuity in the study eye at 54 weeks favoured bevacizumab treatment over standard care. <b>Conclusions</b> Bevacizumab 1.25 mg intavitreous injections given as part of a six weekly variable retreatment regimen is superior to standard care (pegaptanib sodium, verteporfin, sham), with low rates of serious ocular adverse events. Treatment improved visual acuity on average at 54 weeks. <b>Trial registration number</b> Current controlled trials ISRCTN83325075
Protein–protein interaction in insulin signaling and the molecular mechanisms of insulin resistance
Authors: Antti Virkamäki, Kohjiro Ueki, C. Ronald Kahn
Journal: Journal of Clinical Investigation (1999)

Perspective Figure 1Schematic illustration of major signaling pathways of insulin action.The phosphorylated insulin receptor binds and phosphorylates IRS proteins and Shc, which bind differentially to various downstream signaling proteins.PI3-kinase is critical for metabolic actions of insulin, such as glucose transport, glycogen synthesis, and protein synthesis, whereas Grb-2/SOS complex, which activates the MAP kinase cascade, is critical in mitogenic response.PI3-kinase probably modulates the mitogenic response as well.This series continues from the March 1999, no.6, issue.
The kinase Pyk2 is involved in renal fibrosis by means of mechanical stretch–induced growth factor expression in renal tubules
Authors: Kazuhiro Sonomura, Mitsuhiko Okigaki, Taikou Kimura, Eiko Matsuoka, Yayoi Shiotsu, Takaomi Adachi, Hiroshi Kado, Ryo Ishida, Tetsuro Kusaba, Hiroaki Matsubara, Yasukiyo Mori
Journal: Kidney International (2011)
The Role of Genetics in Clinical Medicine.
Authors: Alexander G. Beam
Journal: Annals of Internal Medicine (1967)

s1 May 1967The Role of Genetics in Clinical Medicine.Alexander G. Beam, M.D., F.A.C.P.Alexander G. Beam, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-66-5-1029_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe spectacular advances in our knowledge of the nature of the gene have accentuated our curiosity in the relevance of these findings to our understanding of human disease. The prescient insights of Archibald Gar rod early in the century have been amply confirmed. Genetical theory has provided a unifying concept for a bewildering number of bizarre medical sports. Detection of the genetically controlled primary defect points, in many instances, to the institution of rational therapy and "puts paid" to the archaic aphorism that the only cure for the hereditary disorders is the grave.The application of genetical principles in the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, New York PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1967Volume 66, Issue 5Page: 1029-1029KeywordsClinical geneticsSports ePublished: 1 December 2008 Issue Published: 1 May 1967 PDF downloadLoading ...
OC-003 Genome-wide Epigenetic Analysis In Childhood-onset Crohn’s Disease Implicates Mir21
Authors: AT Adams, NA Kennedy, R Hansen, NT Ventham, KR O’Leary, HE Drummond, CL Noble, E El-Omar, RK Russell, DC Wilson, ER Nimmo, GL Hold, J Satsangi
Journal: Gut (2014)

<h3>Introduction</h3> DNA methylation influences transcriptional activity and marks sites of active transcription. Technological developments allow the rapid assessment of methylation state at 450,000 sites across the genome. The aim of this study was to identify genes with a possible role in Crohn’s disease pathogenesis, and candidate genes for methylation based diagnostic biomarkers. <h3>Methods</h3> Using the Illumina 450k platform we analysed genome-wide DNA methylation in symptomatic children who underwent diagnostic colonoscopy, half of whom were diagnosed with CD and half had no pathology. Replication was performed in children with established CD vs. symptomatic non-disease controls. Further targeted replication by pyrosequencing was performed in adults with CD vs. healthy controls, with qPCR and microarray data to analyse expression. <h3>Results</h3> Meta-analysis of the combined paediatric datasets (n = 66) identified 165 individual CpGs with epigenome-wide significance (Bonferroni correction) and 138 differentially methylated regions (DMR). Methylation changes were significantly enriched (p &lt; 0.0001) in proximity to loci implicated by genome-wide association studies (GWAS). The strongest result by each approach was MicroRNA 21, within the autophagy gene VMP1 (p = 1.2 × 10<sup>–14</sup>), 48 kb from GWAS SNP rs1292053. In adults with CD we replicated MIR21 hypomethylation (p = 6.6 × 10<sup>–5</sup>, n = 172), and showed increased expression in blood (p &lt; 0.005, n = 66). Intestinal expression increased with inflammation in CD (p = 1.4 × 10<sup>–6</sup>, n = 99) but not controls (n = 73). Linear discriminant analysis of methylation in the paediatric discovery cohort accurately predicted disease state in the paediatric replication cohort (94% sensitivity, 100% specificity) based on methylation at two CpG sites. <h3>Conclusion</h3> MIR21 emerges as a target for further investigation based on methylation and expression, further strengthened by other positive findings – notably dysregulation in dysplasia and colorectal cancer in IBD, an established role in T-cell differentiation, and protection from DSS-induced fatal colitis by MIR21 knockout. These data demonstrate a novel approach for identifying biological variations associated with germ-line variants identified by GWAS, and demonstrate translational potential for biomarker development and therapeutic target discovery. <h3>Disclosure of Interest</h3> None Declared.
Thrombocytopathy associated with autoimmune haemolytic anaemia.
Authors: N H Russell, J P Keenan, M A Frais
Journal: BMJ (1978)

et a15 and could have accounted for the lung lesion seen in our patient.Nevertheless, the peculiar evolution of this case, in which the vascular lesions suggesting periarteritis nodosa preceded the other clinical signs typical of relapsing polychondritis, tends to confirm the suggestion by MacAdam et a13 and Neild et a15 that at least some patients with relapsing polychondritis fall into the range of systemic vasculitis.
The potential impacts of climate variability and change on air pollution-related health effects in the United States.
Authors: S M Bernard, J M Samet, A Grambsch, K L Ebi, I Romieu
Journal: Environmental Health Perspectives (2001)

Climate change may affect exposures to air pollutants by affecting weather, anthropogenic emissions, and biogenic emissions and by changing the distribution and types of airborne allergens. Local temperature, precipitation, clouds, atmospheric water vapor, wind speed, and wind direction influence atmospheric chemical processes, and interactions occur between local and global-scale environments. If the climate becomes warmer and more variable, air quality is likely to be affected. However, the specific types of change (i.e., local, regional, or global), the direction of change in a particular location (i.e., positive or negative), and the magnitude of change in air quality that may be attributable to climate change are a matter of speculation, based on extrapolating present understanding to future scenarios. There is already extensive evidence on the health effects of air pollution. Ground-level ozone can exacerbate chronic respiratory diseases and cause short-term reductions in lung function. Exposure to particulate matter can aggravate chronic respiratory and cardiovascular diseases, alter host defenses, damage lung tissue, lead to premature death, and possibly contribute to cancer. Health effects of exposures to carbon monoxide, sulfur dioxide, and nitrogen dioxide can include reduced work capacity, aggravation of existing cardiovascular diseases, effects on pulmonary function, respiratory illnesses, lung irritation, and alterations in the lung's defense systems. Adaptations to climate change should include ensuring responsiveness of air quality protection programs to changing pollution levels. Research needs include basic atmospheric science work on the association between weather and air pollutants; improving air pollution models and their linkage with climate change scenarios; and closing gaps in the understanding of exposure patterns and health effects.
P64Exosomal microRNA signature predicts future ischemic events in hypercholesterolemic patients
Authors: R Suades, T Padro, R Alonso, P Mata, L Badimon
Journal: Cardiovascular Research (2014)

Purpose: High LDL-cholesterol plasma levels constitute an independent risk factor for the pathogenesis of atherothrombotic cardiovascular (CV) disease. We aimed to study miRNAs, non-coding RNAs involved in post-transcriptional regulation of gene expression, in circulating exosomes as prognostic markers of future cardiovascular events.
Therapeutic effect of cortistatin on experimental arthritis by downregulating inflammatory and Th1 responses
Authors: E. Gonzalez-Rey, A. Chorny, R. G Del Moral, N. Varela, M. Delgado
Journal: Annals of the Rheumatic Diseases (2006)

<b>Background:</b> Rheumatoid arthritis is a chronic autoimmune disease of unknown aetiology characterised by chronic inflammation in the joints and subsequent destruction of the cartilage and bone. <b>Aim:</b> To propose a new strategy for the treatment of arthritis based on the administration of cortistatin, a newly discovered neuropeptide with anti-inflammatory actions. <b>Methods:</b> DBA/1J mice with collagen-induced arthritis were treated with cortistatin after the onset of disease, and the clinical score and joint histopathology were evaluated. Inflammatory response was determined by measuring the levels of various inflammatory mediators (cytokines and chemokines) in joints and serum. T helper cell type 1 (Th1)-mediated autoreactive response was evaluated by determining the proliferative response and cytokine profile of draining lymph node cells stimulated with collagen and by assaying the content of serum autoantibodies. <b>Results:</b> Cortistatin treatment significantly reduced the severity of established collagen-induced arthritis, completely abrogating joint swelling and destruction of cartilage and bone. The therapeutic effect of cortistatin was associated with a striking reduction in the two deleterious components of the disease—that is, the Th1-driven autoimmune and inflammatory responses. Cortistatin downregulated the production of various inflammatory cytokines and chemokines, decreased the antigen-specific Th1-cell expansion, and induced the production of regulatory cytokines, such as interleukin 10 and transforming growth factor β1. Cortistatin exerted its effects on synovial cells through both somatostatin and ghrelin receptors, showing a higher effect than both peptides protecting against experimental arthritis. <b>Conclusion:</b> This work provides a powerful rationale for the assessment of the efficacy of cortistatin as a novel therapeutic approach to the treatment of rheumatoid arthritis.
c-Myc and eIF4F Constitute a Feedforward Loop That Regulates Cell Growth: Implications for Anticancer Therapy
Authors: Chen-Ju Lin, Abba Malina, Jerry Pelletier
Journal: Cancer Research (2009)

The Myc/Max/Mad family of transcription factors and the eukaryotic initiation factor 4F (4F) complex play fundamental roles in regulating cell growth, proliferation, differentiation, and oncogenic transformation. Recent findings indicate that the role of Myc during cell growth and proliferation is linked to an increase in eIF4F activity in a feedforward relationship, providing a possible molecular mechanism of cell transformation by Myc. Developing therapeutics to inhibit eIF4F and/or Myc could be a potential treatment for a wide range of human cancers.
Tubular epithelial-myofibroblast transdifferentiation in progressive tubulointerstitial fibrosis in 5/6 nephrectomized rats
Authors: Yee-Yung Ng, Tung-Po Huang, Wu-Chang Yang, Zheng-Ping Chen, An-Hang Yang, Wei Mu, David J. Nikolic-Paterson, Robert C. Atkins, Hui Y. Lan
Journal: Kidney International (1998)
THE EFFECT OF FEEDING SUGAR UPON THE ESTERASE CONTENT OF THE BLOOD SERUM AND ORGANS IN PHOSPHORUS POISONING
Authors: J. P. Simonds
Journal: The Journal of Experimental Medicine (1918)

1. Clear, filtered glycerol extracts of chopped liver, spleen, and kidney contain an ester-splitting ferment. 2. The esterase content of extracts of the liver and spleen of normal dogs is reasonably constant. 3. The amount of esterase in the liver does not appear to vary to any great extent from the normal, in poisoning with chloroform and phosphorus. 4. Feeding large quantities of sugar and increasing the amount of glycogen in the liver is accompanied by a marked increase in the esterase content of that organ. This increase is also evident in phosphorus-poisoned animals which have been fed large amounts of sugar. 5. The feeding of sugar does not prevent the increase in esterase in the blood serum of animals poisoned with phosphorus. 6. The esterolytic power of extracts of the kidney varies considerably in different dogs.
Risk of Cocaine-Induced Myocardial Infarction During Sport
Authors: Arthur J. Siegel
Journal: Circulation (2000)

In the Determinants of Myocardial Infarction Onset Study, Mittleman et al 1,2 demonstrated triggering effects of myocardial infarction in the hour immediately after cocaine use and strenuous exercise, with 23.7-and 5.9-fold increases over baseline, respectively
The prediction of risk of recurrence and time to recurrence of hepatocellular carcinoma after orthotopic liver transplantation: A pilot study
Authors: J W Marsh, I Dvorchik, M Subotin, V Balan, J Rakela, E P Popechitelev, V Subbotin, A Casavilla, B I Carr, J J Fung, S Iwatsuki
Journal: Hepatology (1997)

Orthotopic liver transplantation (OLTx) in the presence of hepatocellular carcinoma (HCC) has been complicated by high recurrence rates. The ability to determine the risk and timing of HCC recurrence on an individual basis would greatly aid in the candidate selection process resulting in a more efficient use of donated organs and allow the individualization and better evaluation of adjuvant chemotherapy. The 214 patients who underwent OLTx in the presence of HCC were analyzed. From the 178 patients who survived more than 150 days, 71 (40%) have suffered HCC recurrence. Based on five risk factors, that is, gender, tumor number, lobar tumor distribution, tumor size, grade of vascular invasion, artificial neural network models predicting the likelihood of HCC recurrence within 1, 2, and 3 consecutive years after transplantation were developed. Based on model predictions, those combinations of risk factors that should/should not lead to recurrence were generated, allowing stratification of patients into the following three groups: 1) patients who should not suffer HCC recurrence and who should not need adjuvant therapy, 2) patients who will suffer recurrence and for whom postoperative chemotherapy significantly prolonged survival (but did not prevent recurrence), and 3) patients who may or may not suffer HCC recurrence and whose recurrence may be prevented by adjuvant chemotherapy. The outcome of OLTx for patients with HCC can be prognosticated based on a number of clinical variables. If verified through multicenter trials, these models could be made available to transplantation programs performing OLTx in the presence of HCC.
TCT-376 Is Cardiac Tamponade Associated With Adverse Outcome in Patients Treated by PCI for Chronic Total Coronary Occlusion. An Insight From a Large French Registry Including More than 1,500 Patients.
Authors: Fouad Hage, Oscar Tavolaro, Philippe Garot, Thierry Lefevre, Thomas Hovasse, Thierry Unterseeh, Hakim Benamer, Bernard Chevalier, Marie-Claude Morice, Yves Louvard
Journal: Journal of the American College of Cardiology (2013)
Association of NIDDM and Hearing Loss
Authors: Dayna S Dalton, Karen J Cruickshanks, Ronald Klein, Barbara EK Klein, Terry L Wiley
Journal: Diabetes Care (1998)

OBJECTIVE To evaluate the association of NIDDM with hearing loss in a large population-based study. RESEARCH DESIGN AND METHODS Data from population-based longitudinal studies of aging conducted in Beaver Dam, Wisconsin, were used in these analyses. Hearing thresholds were determined by pure-tone air- and bone-conduction audiometry performed by trained technicians following American Speech-Language-Hearing Association specifications. Hearing loss was defined as the pure-tone average of the frequencies 500, 1,000, 2,000, and 4,000 Hz &amp;gt; 25 decibels hearing level in the worse ear. Diabetes status was determined by self-report of physician-diagnosed diabetes or by elevated glucose or glycated hemoglobin levels at examination. RESULTS Of 3,571 study participants, 344 were classified as having NIDDM. Subjects with NIDDM were more likely to have a hearing loss than were subjects without diabetes (59 vs. 44%). After results were adjusted for age, this difference was not statistically significant. After individuals with hearing loss patterns inconsistent with presbycusis were excluded, there was an association between NIDDM and hearing loss when controlling for potential confounders (odds ratio [OR] 1.41, 95% CI 1.05–1.88). There was no association between duration of diabetes or glycemic control and hearing loss. Individuals with NIDDM and nephropathy were more likely to have a hearing loss than were those with NIDDM but no nephropathy (OR 2.28, 95% CI 1.04–5.00). CONCLUSIONS These data are suggestive of a weak association between NIDDM and hearing loss.
Sexual Science and the Law
Authors: Virginia A. Sadock
Journal: JAMA (1993)

Richard Green has written a timely and interesting book about the interface between sexual behavior and the legal system. Dr Green is a professor of psychiatry at the University of California, Los Angeles, and he also holds a law degree. In writing this book, he has drawn on his experience as a psychiatric researcher in sexuality and on his participation as an expert witness in court cases involving sexual issues. The topics he discusses are emotionally charged and have evoked intense reactions in our society. They include abortion, pornography, prostitution, sex education, homosexuality, and the treatment of sex offenders. He also addresses legal questions, including the constitutional right to sexual privacy, the implications of the age of consent vs meaningful consent (which he calls "a psychological concept"), and approaches for granting equal rights to people who are frequently discriminated against, such as homosexuals. It is the author's view that, although
Disappearance of Microalbuminuria in a Patient With Type 2 Diabetes and the Metabolic Syndrome in the Setting of an Intense Exercise and Dietary Program With Sustained Weight Reduction
Authors: Sonja K. Fredrickson, Thomas J. Ferro, Andrew C. Schutrumpf
Journal: Diabetes Care (2004)

e present a patient with the metabolic syndrome who demonstrated microalbuminuria, an index of cardiovascular risk (1), at the time of presentation.The patient was treated with an intensive regimen of dietary and exercise changes, and all diagnostic criteria for the metabolic syndrome resolved, followed by resolution of the microalbuminuria. HISTORY AND EXAMINATION-A 43-year-old man presented to his primary care physician for a "new patient evaluation."Xerostomia, polydipsia, and polyuria, which had been attributed to chronic rhinosinusitis, were noted.A normal fasting blood glucose level had been recorded just before the onset of these symptoms, ϳ5 years prior the visit.Physical examination and laboratory evaluation revealed the presence of metabolic syndrome, encompassing the following diagnoses: central obesity, hypertension, type 2 diabetes, hypertriglyceridemia, and low HDL (data below).The patient was started on aspirin at 81 mg once per day and glipizide extended release at 5.0 mg once per day.He was also told to lose weight through a program of exercise and dietary interventions.
POST-PROCEDURAL DABIGATRAN VERSUS STANDARD ANTICOAGULATION IN ABLATION FOR ATRIAL FIBRILLATION
Authors: Jeffrey Lin, Bradley Knight, Prashant Bhave, Martha Bohn, Alexandru Chicos, Evaldas Giedrimas, Jeffrey Goldberger, Leonard Ilkhanoff, Susan Kim, Albert Lin, Taral Patel, Sharon Shen, Rod Passman
Journal: Journal of the American College of Cardiology (2013)
Variability of Total and Free IgE and IgE Receptor Expression in Allergic Subjects in and out of an Allergen Season
Authors: M. Carlsson, S. Larsson-Faria, K. Behrens, C. Lindqvist, K. Buttler, S. Keeler, A. Sjölander, L. Thorell, P. Eriksson
Journal: Journal of Allergy and Clinical Immunology (2011)