tbuckley/cabot-search huggingface dataset:
Managing Patients with Psoriatic Disease: The Diagnosis and Pharmacologic Treatment of Psoriatic Arthritis in Patients with Psoriasis
Authors: Philip J. Mease, April W. Armstrong
Journal: Drugs (2014)

Psoriatic arthritis (PsA) is a chronic, systemic inflammatory disease. Up to 40 % of patients with psoriasis will go on to develop PsA, usually within 5–10 years of cutaneous disease onset. Both conditions share common pathogenic mechanisms involving genetic and environmental factors. Because psoriasis is typically present for years before PsA-related joint symptoms emerge, dermatologists are in a unique position to detect PsA earlier in the disease process through regular, routine screening of psoriasis patients. Distinguishing clinical features of PsA include co-occurrence of psoriatic skin lesions and nail dystrophy, as well as dactylitis and enthesitis. Patients with PsA are usually seronegative for rheumatoid factor, and radiographs may reveal unique features such as juxta-articular new bone formation and pencil-in-cup deformity. Early treatment of PsA with disease-modifying anti-rheumatic drugs has the potential to slow disease progression and maintain patient quality of life. Optimally, a single therapeutic agent will control both the skin and joint psoriatic symptoms. A number of traditional treatments used to manage psoriasis, such as methotrexate and cyclosporine, are also effective for PsA, but these agents are often inadequately effective, temporary in benefit and associated with significant safety concerns. Biologic anti-tumour necrosis factor agents, such as etanercept, infliximab and adalimumab, are effective for treating patients who have both psoriasis and PsA. However, a substantial number of patients may lose efficacy, have adverse effects or find intravenous or subcutaneous administration inconvenient. Emerging oral treatments, including phosphodiesterase 4 inhibitors, such as apremilast, and new biologics targeting interleukin-17, such as secukinumab, brodalumab and ixekizumab, have shown encouraging clinical results in the treatment of psoriasis and/or PsA. Active and regular collaboration of dermatologists with rheumatologists in managing patients who have psoriasis and PsA is likely to yield more optimal control of psoriatic dermal and joint symptoms, and improve long-term patient outcomes.
Abstract A73: Understanding specificity in Notch receptor signaling
Authors: Alisa Bell, Heidi Okamura, David Keane, Samantha Perino, Jeanine Lorusso, Jeno Gyuris, Ronan O'Hagan
Journal: Cancer Research (2009)

Abstract Notch signaling plays an integral role in cell growth and differentiation. Alterations in Notch signaling caused by mutations in receptors, amplification of pathway components, and increased expression of receptors and ligands have been shown to be important in tumor growth and maintenance. There are multiple Notch receptors and multiple ligands that can potentially interact to elicit a signal. Furthermore, many tumor cells express more than one Notch receptor. The complexity of these interactions and the potential specificity of resultant signals necessitate further understanding of the context of signaling to better determine how to treat Notch driven tumors. To this end, we have developed cell based reporter assays to investigate total Notch signal from cells stimulated by cell surface ligands in a co-culture system or by plate-bound ligands. In addition, we have developed assays to determine signal from individual Notch receptors. Human cancer cell lines that express multiple Notch receptors were engineered to express a Notch-dependent luciferase reporter. These cells were stimulated with plate-bound or cell surface ligands and assayed for activation of the Notch receptors. Subsequently, specific blocking of individual Notch receptors with antibodies was used to determine which specific receptors acted as effectors of Notch signal. Understanding both the array of Notch receptors on a particular cell type and more specifically the ability of each receptor to produce active signal will be important in determining how to effectively treat Notch driven tumors. Citation Information: Cancer Res 2009;69(23 Suppl):A73.
Albright's Hereditary Osteodystrophy and Defective G Proteins
Authors: Allen M. Spiegel
Journal: New England Journal of Medicine (1990)

Given the myriad extracellular signals impinging on cells, the number of mechanisms used to convey information to them is surprisingly limited. A common feature is a signal discriminator, better known as a receptor. Often, the receptor is also an intracellular signal generator. Binding of an activating signal to the receptor triggers its intrinsic signal-generating capacity. An exception to this pattern is a large class of cell-surface receptors that are coupled to distinct intracellular signal generators by molecular go-betweens, called G proteins.G proteins are products of a large gene family. They specifically bind guanine nucleotides and hydrolyze the last phosphate . . .
Reduced atherosclerosis in MyD88-null mice links elevated serum cholesterol levels to activation of innate immunity signaling pathways
Authors: Harry Björkbacka, Vidya V Kunjathoor, Kathryn J Moore, Stephanie Koehn, Christine M Ordija, Melinda A Lee, Terry Means, Kristen Halmen, Andrew D Luster, Douglas T Golenbock, Mason W Freeman
Journal: Nature Medicine (2004)
Electrophysiologic characteristics, electropharmacologic responses and radiofrequency ablation in patients with decremental accessory pathway
Authors: Shih-Ann Chen, Ching-Tai Tai, Chern-En Chiang, Shih-Huang Lee, Zu-Chi Wen, Chuen-Wang Chiou, Kwo-Chang Ueng, Yi-Jen Chen, Wen-Chung Yu, Jin-Long Huang, Mau-Song Chang
Journal: Journal of the American College of Cardiology (1996)
Antibody-Maytansinoid Conjugates Designed to Bypass Multidrug Resistance
Authors: Yelena V. Kovtun, Charlene A. Audette, Michele F. Mayo, Gregory E. Jones, Heather Doherty, Erin K. Maloney, Hans K. Erickson, Xiuxia Sun, Sharon Wilhelm, Olga Ab, Katharine C. Lai, Wayne C. Widdison, Brenda Kellogg, Holly Johnson, Jan Pinkas, Robert J. Lutz, Rajeeva Singh, Victor S. Goldmacher, Ravi V.J. Chari
Journal: Cancer Research (2010)

Conjugation of cytotoxic compounds to antibodies that bind to cancer-specific antigens makes these drugs selective in killing cancer cells. However, many of the compounds used in such antibody-drug conjugates (ADC) are substrates for the multidrug transporter MDR1. To evade the MDR1-mediated resistance, we conjugated the highly cytotoxic maytansinoid DM1 to antibodies via the maleimidyl-based hydrophilic linker PEG(4)Mal. Following uptake into target cells, conjugates made with the PEG(4)Mal linker were processed to a cytotoxic metabolite that was retained by MDR1-expressing cells better than a metabolite of similar conjugates prepared with the nonpolar linker N-succinimidyl-4-(maleimidomethyl)cyclohexane-1-carboxylate (SMCC). In accord, PEG(4)Mal-linked conjugates were more potent in killing MDR1-expressing cells in culture. In addition, PEG(4)Mal-linked conjugates were markedly more effective in eradicating MDR1-expressing human xenograft tumors than SMCC-linked conjugates while being tolerated similarly, thus showing an improved therapeutic index. This study points the way to the development of ADCs that bypass multidrug resistance.
Abstract 388: Morphological assessment of tumor-associated vessels: Automated image processing of whole tumor sections in invasive breast cancer.
Authors: Elham Fakhrejahani, Yasufumi Asao, Iku Yamaga, Masae Torii, Masahiro Takada, Toshiyuki Kitai, Tomoharu Sugie, Masakazu Toi
Journal: Cancer Research (2013)

Abstract Clinical benefit of anti-angiogenic therapies in different cancers is a result of normalizing the tumor vasculature by these agents. However, tumor vascular imaging modalities in human cancers are in their early evaluating phases. Photoacoustic mammography (PAM) is a newly introduced technique which can image the hemoglobin distribution and oxygenation state inside breast tissue with high spatial resolution. We have previously presented the oxygenation data of our first study in breast cancers by PAM in European Congress of Radiology (ECR) 2011. Here we report the morphological assessment of tumor-associated vessels in 81 histological sections of 20 invasive breast carcinomas. The histological slides were scanned with the magnification of 200 after CD31 immunohistochemical staining. For automated CD31 analysis, 105 jpeg files were extracted from each virtual slide and were changed to binary images with Image Pro-Plus 7.0 software. The optimal hue, saturation and intensity (HSI) of stained structures was selected for each virtual slide. Each binary file was divided into 16 squares of 0.84mm x 0.84 mm size. Total number, area and length of stained structures were calculated in each square. Patients’ age ranged from 36 to 84 years.19 cases were invasive ductal carcinomas and 1 case was invasive lobular carcinoma. Nine cases were luminal A, 9 cases luminal B and 2 cases were HER-2 subtype. For Ki67 scoring ndex,5 cases had &amp;lt;5%, 9 cases between 5-20% and 6 cases had more than 20%. There was a wide heterogeneity among total of 2.95 x10 6 analyzed tumor-associated vessels in 81 histological sections. Table-1 shows the characteristics and distribution pattern. Total number of vessels/mm2 of breast tissue Total area of vessels (μm2)/mm2 of breast tissue Total perimeter of vessels (μm)/mm2 of breast tissue Perimeter/vessel (μm) Area/vessel (μm2) Min 4.6 218.4 65.5 17.8 37.7 Max 87 4369.8 1274.5 45.4 139.3 Average (+SD) 30.7 (+19) 1573.9 (+1060.8) 448.3 (+286.7) 28.9 (+ 4.2) 71.6 (+ 17.9) Additional analysis of shape and pericyte coverage in these vessels is on its way. In conjunction with oxygenation data obtained by PAM,this can be used as a tumor vessel normalization assessment tool which can be used as a biomarker in anti-angiogenic treatments in breast cancers. Citation Format: Elham Fakhrejahani, Yasufumi Asao, Iku Yamaga, Masae Torii, Masahiro Takada, Toshiyuki Kitai, Tomoharu Sugie, Masakazu Toi. Morphological assessment of tumor-associated vessels: Automated image processing of whole tumor sections in invasive breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 388. doi:10.1158/1538-7445.AM2013-388
Red blood cell distribution width predicts long‐term outcome regardless of anaemia status in acute heart failure patients
Authors: Domingo A. Pascual‐Figal, Juan C. Bonaque, Belen Redondo, Cesar Caro, Sergio Manzano‐Fernandez, Jesús Sánchez‐Mas, Iris P. Garrido, Mariano Valdes
Journal: European Journal of Heart Failure (2009)
Retinal Injuries from a Handheld Laser Pointer
Authors: Stefan Wyrsch, Philipp B. Baenninger, Martin K. Schmid
Journal: New England Journal of Medicine (2010)

To the Editor: Handheld laser pointers are commonly used in lecture halls and are considered to be harmless and safe.1 However, laser pointers can cause severe eye injury, as demonstrated by the case of a 15-year-old boy. The boy had ordered a handheld laser pointer with green light on the Internet to use as a toy for popping balloons from a distance and burning holes into paper cards and his sister's sneakers. The boy's life changed when he was playing with his laser pointer in front of a mirror to create a “laser show,” during which the laser beam hit . . .
Effects of streptokinase, urokinase, and recombinant tissue plasminogen activator on platelet aggregability and stability of platelet aggregates
Authors: W. Terres, S. Umnus, D. G Mathey, W. Bleifeld
Journal: Cardiovascular Research (1990)

The aim of the study was to evaluate the effects of streptokinase, urokinase and recombinant tissue plasminogen activator (TPA) on platelet aggregability and metabolism and the stability of preformed platelet aggregates.The experiments (n = 15 for each condition) were performed on citrated plasma or on platelet suspensions in phosphate buffered saline, both with a standardised platelet count of 250 x 10(9).litre-1.were healthy volunteers.With both ADP (1 mumol.litre-1) and collagen (1 mg.litre-1) as aggregating agents, streptokinase at greater than or equal to 10(5) units.litre-1 led to reduction in the rate of platelet aggregation. With collagen and in most instances with ADP, this was associated with a decreased extent of aggregation, though in five out of 30 cases with ADP as aggregating agent, a conversion from reversible to irreversible aggregation occurred with streptokinase. Urokinase inhibited platelet aggregation at greater than or equal to 3 x 10(5) units.litre-1 with both aggregating agents. TPA inhibited aggregation at greater than or equal to 1 mg.litre-1 with ADP and at greater than or equal to 3.3 mg.litre-1 with collagen as aggregating agent. The inhibitory effect was still present when the platelets were suspended in saline. Platelet synthesis of thromboxane on stimulation with collagen, and of c-AMP on stimulation with prostaglandin E1, was markedly reduced by either agent. The stability of platelet aggregates, as assessed photometrically during a 90 min exposure to stirring stress, increased when streptokinase or urokinase was added to platelet rich plasma, but remained uninfluenced with TPA.Urokinase and TPA inhibited platelet aggregability uniformly and in a dose dependent manner. Streptokinase inhibited platelet aggregation in most instances, but led to a stimulation of aggregation in a minority of cases. These effects of the thrombolytic agents on platelets might have an influence on the occurrence of bleeding and of reocclusion after thrombolytic therapy.
Book Review Principles and Practice of Gastrointestinal Oncology Second edition. Edited by David P. Kelsen, John M. Daly, Scott E. Kern, Bernard Levin, Joel E. Tepper, and Eric Van Cutsem. 749 pp., illustrated. Philadelphia, Lippincott Williams &amp; Wilkins, 2008. $199. 978-0-7817-7617-2
Authors: David Cunningham
Journal: New England Journal of Medicine (2008)
Stroke After Roller Coaster-Induced Carotid Compression
Authors: Max S. Scheer
Journal: JAMA (1979)

TRAUMATIC thrombosis of the internal carotid artery has been reported. Such cases have been due to blunt neck injury followed by spreading thrombosis and subsequent cerebral embolization.<sup>1,2</sup>Carotid artery compression caused by diagnostic carotid compression tonography and ocular pneumoplethysmography have also been described.<sup>3</sup>We describe a previously healthy teenage girl who had a stroke after riding a roller coaster in which she was upside down, supported by a padded metal shoulder support resembling a horse collar. <h3>Report of a Case</h3> A 13-year-old girl was admitted to the Morristown Memorial Hospital on Aug 27, 1978, with the chief complaint of headache, right hemiparesis, and difficulty speaking. Her speech defect was first noted as she stepped off a roller coaster ride two days earlier, but cleared spontaneously after one hour. However, her headache persisted and the following morning she was seen by her physician, who found no focal neurologic signs
Positron emission tomography in venous ulceration and liposclerosis: study of regional tissue function.
Authors: N F Hopkins, T J Spinks, C G Rhodes, A S Ranicar, C W Jamieson
Journal: BMJ (1983)

Oxygen-15 administered by continuous inhalation and emission computed tomography were used to study regional tissue oxygen utilisation and blood flow in the limbs of 11 patients with venous ulceration and five patients with liposclerosis due to venous insufficiency. The results showed increased blood flow and appreciably reduced fractional oxygen extraction in the diseased tissues. These findings indicated a local, functional shunting of blood through the abnormal microcirculation of the skin and subcutaneous tissues. This may be an important factor in the aetiology of the skin changes seen in patients with calf muscle pump failure.
Abstract 3014: Implication of ΔNp73 isoform in drug resistance.
Authors: Beatriz Soldevilla, Marta Rodríguez, Coral San Millán, Félix Bonilla, Gemma Domínguez
Journal: Cancer Research (2013)

Abstract Background: Aberrant expression of ▵Np73 has been associated with shorten cancer patient survival. We evaluate here whether this event could be due to the induction of drug resistance mechanisms. Experimental Design: HCT116 colon cancer cell line transfected with a vector containing ▵Np73 or a mock vector were treated with oxaliplatin and checked for the viability by MTT, Flow-citometry, TUNEL assay and Caspase-3 protein expression levels. Additionally, we determined in 77 colon cancer patients the expression of ΔNp73 and their putative target genes related with drug resistance ABCB1, HMGB1 and CASP1 by quantitative real-time RT-PCR. Disease-free survival (DFS) and overall survival (OS) were examined in each patient. Results: Ectopic expression of ▵Np73 significantly associated with a higher viability after oxaliplatin exposure. Positive correlations were observed between the expression levels of ▵Np73 variants and HMGB1. A trend was also observed for ABCB1. Overexpression of ΔNp73 isoforms predicted shortened OS (p = 0.05). High levels of ABCB1 and HMGB1 associated with shorter OS (p = 0.04 and p = 0.05, respectively). Multivariate analysis showed that, in addition to the tumor stage, ABCB1 and HMGB1 had independent relationships with OS (p = 0.008). Conclusions: The association of the upregulation of ▵Np73 with higher cancer cell viability after oxaliplatin treatment along with the fact that it could trigger HMG1 and ABCB1 in vivo, supports the hyphotesis that the shorten survival observed in those cancer patients showing overexpression of ▵Np73 could be due to the induction of drug resistance processes by this isoform. Citation Format: Beatriz Soldevilla, Marta Rodríguez, Coral San Millán, Félix Bonilla, Gemma Domínguez. Implication of ΔNp73 isoform in drug resistance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3014. doi:10.1158/1538-7445.AM2013-3014
Internists for Nursing Homes
Authors: HERBERT A. LINTS
Journal: Annals of Internal Medicine (1980)

Letters and Corrections1 September 1980Internists for Nursing HomesHERBERT A. LINTS, M.D.HERBERT A. LINTS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-93-3-512_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Recent editorials and letters in your journal on geriatric problems have centered on speciality training for future physicians. All have neglected what needs to be done now about patients in nursing homes. Over 1 million persons now live in such facilities throughout the country, but internist responsibility for their care is the exception rather than the rule. Nursing home patients and nursing home staff should have the services of internists. We should not be excused from this responsibility because surveys in medical schools show negative attitudes towards aging. Our profession should be mature enough to meet the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1980Volume 93, Issue 3Page: 512-512KeywordsAgingForecastingGeriatricsNursing homes Issue Published: 1 September 1980 PDF downloadLoading ...
Sodium Channel Blockers Identify Risk for Sudden Death in Patients With ST-Segment Elevation and Right Bundle Branch Block but Structurally Normal Hearts
Authors: Ramon Brugada, Josep Brugada, Charles Antzelevitch, Glenn E. Kirsch, Domenico Potenza, Jeffrey A. Towbin, Pedro Brugada
Journal: Circulation (2000)

Background —A mutation in the cardiac sodium channel gene (SCN5A) has been described in patients with the syndrome of right bundle branch block, ST-segment elevation in leads V1 to V3, and sudden death (Brugada syndrome). These electrocardiographic manifestations are transient in many patients with the syndrome. The present study examined arrhythmic risk in patients with overt and concealed forms of the disease and the effectiveness of sodium channel blockers to unmask the syndrome and, thus, identify patients at risk. Methods and Results —The effect of intravenous ajmaline (1 mg/kg), procainamide (10 mg/kg), or flecainide (2 mg/kg) on the ECG was studied in 34 patients with the syndrome and transient normalization of the ECG (group A), 11 members of 3 families in whom a SCN5A mutation was associated with the syndrome and 8 members in whom it was not (group B), and 53 control subjects (group C). Ajmaline, procainamide, or flecainide administration resulted in ST-segment elevation and right bundle branch block in all patients in group A and in all 11 patients with the mutation in group B. A similar pattern could not be elicited in the 8 patients in group B who lacked the mutation or in any person in group C. The follow-up period (37±33 months) revealed no differences in the incidence of arrhythmia between the 34 patients in whom the phenotypic manifestation of the syndrome was transient and the 24 patients in whom it was persistent (log-rank, 0.639). Conclusions —The data demonstrated a similar incidence of potentially lethal arrhythmias in patients displaying transient versus persistent ST-segment elevation and right bundle branch block, as well as the effectiveness of sodium channel blockers to unmask the syndrome and, thus, identify patients at risk.
Paying for bmj.com: Is this measure scientific literature's half open sesame?
Authors: C. C Tam
Journal: BMJ (2003)

Editor—Over the past decade the BMJ has shown its commitment to widening access by providing universally free online content and reduced subscriptions for people in resource limited settings. Given its support for open access, it is regrettable that, in the face of falling paper sales, the journal should opt to squeeze subscriptions for the few years it has left instead of fully adopting the more progressive open access model.1,2

Under the open access model, each article is paid for only once, subsequently becoming freely available to everyone (with internet access). This point is not being lost on funders. In the United States, the Public Access to Scientific Information Act seeks to place all scientific research substantially funded by government in the public domain.3 Currently, the US government spends $45bn annually on scientific research, the results of which are largely unavailable to taxpayers. The privatisation of scientific information by publishers undermines the accountability of funders and the scientific community to the intended beneficiaries of such research—the public.

The BMJ as a leading medical journal can do much more to open the door to scientific information: by influencing competitors, funders, institutions, and individuals, and by working with independent researchers and those in under-resourced settings towards a more equitable form of publication. For the moment, this door remains ajar.
Linear acral pseudolymphomatous angiokeratoma of children (APACHE): Further evidence that APACHE is a cutaneous pseudolymphoma
Authors: Takahiro Kiyohara, Masanobu Kumakiri, Takeo Kawasaki, Akiteru Takeuchi, Hiroaki Kuwahara, Takanori Ueda
Journal: Journal of the American Academy of Dermatology (2003)