tbuckley/cabot-search huggingface dataset:
Abstract 15920: The Prevalence of Atherosclerotic Disease in Those With Connective Tissue Disease as a Function of Age, Race, and Traditional Risk Factors
Authors: Francis J Alenghat
Journal: Circulation (2014)

Background: Atherosclerosis is a multifactorial disease with an intrinsic inflammatory component, but it may also be influenced by systemic inflammation. There is cardiovascular risk associated with rheumatoid arthritis (RA), but there is still a need to clarify the contributions of traditional risk factors in those with inflammatory connective tissue diseases (CTD, which includes RA) in the development of atherosclerotic cardiovascular disease (ASCVD). It would also be useful to identify particular groups of patients that are at disproportionately greater conferred risk for ASCVD owing to their CTD. For these reasons, a cross-sectional analysis of a diverse patient population could help develop finer ASCVD risk estimations in those with and without CTD. Results: A systematically queried warehouse of de-identified data from over a quarter-million adult patients at our urban medical center over the past six years showed that prevalence of ASCVD steadily increases with age, consistent with rates found in other large cohorts, in both white and African-American patients. Amongst the ~9,000 patients with CTD (RA, other inflammatory polyarthropathy, lupus, Sjögren’s syndrome, systemic sclerosis, dermatomyositis, polymyositis), the overall prevalence of ASCVD was higher than amongst those without CTD with a rate ratio of 1.9 [95% CI 1.8-2.1] for white patients and 3.3 [95% CI 3.1-3.5] for African-American patients. Subgroup analysis revealed that the rate ratio was particularly high for young adults, and especially young African-American patients (ages 18-44; rate ratio for women: 10.7 [95% CI 8.5-13.5], for men: 9.9 [95% CI 6.8-14.5]). Rate ratios of ASCVD in those with vs. without CTD declined with age as traditional risk factors became more prevalent. Importantly, in those without any documented traditional risk factors (smoking, hypertension, diabetes, dyslipidemia), a diagnosis of ASCVD was found nearly three times more frequently in those with CTD than without [rate ratio 2.9, 95% CI 2.4-3.5]. Conclusions: CTD is associated with increased ASCVD rates, and major traditional risk factors do not fully account for these increased rates. African-Americans and young adults have a disproportionately strengthened association between CTD and ASCVD.
EGFR mutation and striking response to gefitinib in a patient with leptomeningeal carcinomatosis and erlotinib-refractory adenocarcinoma lung cancer
Authors: Nicholas W. Choong, Sascha Dietrich, Tanguy Y. Seiwert, Maria S. Tretiakova, Vidya Nallasura, Gareth C. Davies, Stanley Lipkowitz, Aliya N. Husain, Ravi Salgia, Patrick C. Ma
Journal: Cancer Research (2006)

4029  Although various mutations of the epidermal growth factor receptor (EGFR) gene have been identified to confer sensitivity towards the EGFR tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, it is not known if there are mutations that may result in differential activities of the two inhibitors. We describe a 70 year-old Japanese-American never-smoker woman with advanced adenocarcinoma of the lung who developed symptomatic brain metastases while on erlotinib. She failed further chemotherapies, including temozolomide and irinotecan, and subsequently developed extensive symptomatic leptomeningeal carcinomatosis. The patient then demonstrated prompt striking clinical response as early as three weeks of starting monotherapy gefitinib (150mg p.o. daily), which was subsequently confirmed radiographically by repeat CT and MRI. Using laser microdissection (LMD) and EGFR gene sequencing, we identified two heterozygous somatic EGFR mutations, L858R and E884K, in her pretreatment tumor biopsy specimen and tumor cells isolated from her cerebrospinal fluid. In vitro transfection and biochemical studies demonstrated that the novel E884K mutation confers opposite effects in sensitivity to the two EGFR inhibitors. EGFRE884K and EGFRL858R+E884K enhanced the sensitivity of the mutated receptor to gefitinib inhibition. Conversely, the E884K mutation resulted in decreased responsiveness of the receptor to erlotinib, and it significantly abrogated the drug sensitivity conferred by L858R (EGFRL858R+E884K). This study demonstrates that it is possible to have EGFR mutation mediating differential responses to gefitinib and erlotinib. This also represents the first case to describe a striking response to single-agent gefitinib in a patient with leptomeningeal metastases and erlotinib-refractory lung adenocarcinoma.
Atypical fibroxanthoma of the skin.
Authors: TH.M. STARINK, R. HAUSMAN, L. DELDEN, H. NEERING
Journal: British Journal of Dermatology (1977)

Atypical fibroxanthoma is a solitary tumour of the skin, which occurs mostly on sun‐exposed areas in elderly people. The diagnosis can only be made with certainty on the typical histological findings, which suggest a bizarre malignant tumour. Although metastasizing tumours are reported in the literature, the authors believe that the true atypical fibroxanthoma is benign. Correct diagnosis obviates the need for unnecessary radical surgery. The possibility of atypical fibroxanthoma should always be considered when a histologically bizarre tumour is found on sundamaged or irradiation‐damaged skin in elderly patients or on previously traumatized sites. In this paper five cases are added to the 346 cases culled from the literature. Electron microscopic investigations in one case demonstrated cells with delicate cytoplasmic fibrils in small bundles. This does not necessarily suggest filaments of myofibroblasts, as has been previously reported.
Nasal IL-4+CXCR5+CD4+ T follicular helper cell counts correlate with local IgE production in eosinophilic nasal polyps
Authors: Ya-Na Zhang, Jia Song, Hai Wang, Heng Wang, Ming Zeng, Guan-Ting Zhai, Jin Ma, Zhi-Yong Li, Bo Liao, Bao-Feng Wang, Zhen Zhen, Nan Wang, Ping-Ping Cao, Peng Lin, Qin Ning, Zheng Liu
Journal: Journal of Allergy and Clinical Immunology (2015)
Improving the doctor-manager relationship
Authors: David B Nash, Laurence Malcolm, Lyn Wright, Pauline Barnett, Chris Hendry, Francis J Crosson, Rifat A Atun, Hilary Thomas
Journal: BMJ (2003)

<i>The problem with doctor-manager relationships is well studied. The potential for these relationships to harm the working environment and affect organisational performance is acknowledged and understood. The same is not true of possible solutions. To bridge this gap we invited short contributions, and we are publishing a selection of these to start the debate. This is the kind of issue where those from different sides might wish to contest all the potential solutions. We hope so. Please post your responses on bmj.com</i>
STUDIES ON THE MODE OF ACTION OF IRRADIATED ERGOSTEROL
Authors: Walter Bauer, Alexander Marble, Dorothy Claflin
Journal: Journal of Clinical Investigation (1932)

In the first paper of this series (1), we reported that the administration of adequate doses of irradiated ergosterol to normal individuals resulted in definite alterations in the fecal and urinary excretion of calcium and phosphorus. These changes consisted in a gradual fall in the fecal excretion and a gradual rise in the urinary excretion of both elements with little effect on the total balances of either. These findings are best interpreted as signifying increased absorption from the gastro-intestinal tract without an accompanying increased body retention. The fact that irradiated ergosterol acts as a curative agent in calcium deficiency diseases such as rickets and osteomalacia indicates that an increased retention of calcium and phosphorus must take place when it is administered to individuals with such diseases. In order to determine what changes occur in the calcium and phosphorus metabolism of individuals with calcium deficiency diseases when irradiated ergosterol is administered, two such patients were studied in an effort to ascertain whether the action of irradiated ergosterol was in any way different from that which we had observed in normal individuals.
Severe Acute Pancreatitis
Authors: Ajit Singh Kashyap, Kuldip Parkash Anand, Surekha Kashyap
Journal: JAMA (2004)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
ACUTE IDIOPATHIC HYPOPROTHROMBINEMIA, RESPONSE TO MASSIVE DOSES OF VITAMIN K
Authors: I A HEINDL, B G ANDERSON, R D FRIEDLANDER
Journal: Annals of Internal Medicine (1948)

Excerpt In 1941 Rhoads and Fitz-Hugh1 described the first case of hypoprothrombinemia in which the previously accepted causes of vitamin K deficiency, i.e., liver damage and impaired intestinal absorption, seemed to play no major rôle. Thus, they established a new subgroup of the hemorrhagic disorders, namely, idiopathic hypoprothrombinemia. Since then, several similar cases2, 3, 4, 5, 6, 7, 8 have been reported, differing somewhat from one another, but all with a prolonged prothrombin time. The present case report is added to the small group already in the literature because of the dramatic response to large doses of vitamin K. CASE REPORT
Abstract 14657: Andexanet-alfa and PER977 (Arapazine) Correct Blood Loss in a Rabbit Liver Laceration Model - Only Andexanet Reverses Markers of fXa-mediated Anticoagulation
Authors: Stanley Hollenbach, Genmin Lu, Francis DeGuzman, Siusze Tan, Pratikhya Pratikhya, Anjali Pandey, Pamela Conley, John T Curnutte
Journal: Circulation (2014)

As use of oral fXa inhibitors has increased, so has the need for an antidote to treat the major side effect of these drugs - bleeding. Andexanet alfa (AnXa) (PRT064445), a recombinant fXa derivative, reverses fXa inhibitor-mediated anticoagulation in animals and humans by sequestering the fXa inhibitor in a 1:1 molar ratio, reducing both anti-fXa activity and plasma free fraction of fXa inhibitor, and restoring normal thrombin generation, PT, and aPTT. These parameters correlate closely with reduced blood loss in a rivaroxaban-treated rabbit liver laceration model. Aripazine (PER) (PER977; Perosphere, Inc.) is a small molecule that has been reported to reverse the anticoagulant effects of a broad range of anticoagulants (fXa and thrombin inhibitors; heparins) by direct binding. We synthesized PER and compared it to AnXa in this same liver laceration model at PER doses of 0.3, 3 and 30 mg/kg, and observed reductions in blood loss of 27%, 16% and 76%, respectively ( p &lt;0.02 for 30 mg/kg dose only). There was an unexpected dose-responsive, but non-significant, trend toward decreased blood loss in non-anticoagulated rabbits with PER alone, with the 30 mg/kg dose showing a 23% decrease. The reduction in blood loss between the two agents was similar at the highest dose studied (76% decrease for 75 mg AnXa/rabbit [ASH 2012] and 76% decrease for 30 mg/kg PER in this study). PER dose groups, however, did not show reduction in riva-induced increases in PT, aPTT or anti-fXa activity. Moreover, there was no change in total plasma concentration of riva after PER administration compared to the 6-fold increase seen with AnXa due to its high affinity for riva and redistribution of riva from the extravascular to the intravascular compartment. Unlike the ~1:1 molar ratio needed for AnXa to sequester riva, a 30:1 PER:Riva molar ratio was needed to reduce blood loss. While the mechanism of action (MOA) for AnXa has been well characterized in preclinical and clinical studies, the mechanism of prevention of blood loss with PER in this model is unclear. In summary, the MOA of PER differs from that of AnXa, where direct (1:1) binding of AnXa to the fXa inhibitor decreases the free fraction of the anticoagulant, reverses PD markers and restores normal hemostasis. Further investigation of PER is required.
Effect of mechanical bowel preparation with polyethyleneglycol on bacterial contamination and wound infection in patients undergoing elective open colon surgery
Authors: P.R. Fa-Si-Oen, C. Verwaest, J. Buitenweg, H. Putter, J.-W. de Waard, C.J.H. van de Velde, R.M.H. Roumen
Journal: Clinical Microbiology and Infection (2005)
Abstract 17592: The Cardiolipin-targeting Peptide Bendavia Improves Post-ischemic Mitochondrial Energetics by Sustaining Native Respiratory Protein Complexes
Authors: Saame R Shaikh, Fatiha Moukdar, Rick J Alleman, Daniel S Lark, P D Neufer, David Brown
Journal: Circulation (2014)

Bendavia is a cell permeable, mitochondria-targeting peptide currently being tested in clinical trials for acute coronary syndromes, heart failure, and renal disease. In a series of studies, we have shown that Bendavia reduces cellular injury by targeting the mitochondrial inner membrane. In particular, Bendavia targets cardiolipin, a mitochondrial phospholipid that acts as “glue” to hold respiratory protein complex subunits together. In this study, we tested the hypothesis that Bendavia would improve post-ischemic mitochondrial function by sustaining native respiratory protein complexes. We utilized blue native gels (non-denaturing conditions) alongside high-resolution respirometry in permeabilized myocardial fibers to directly link changes in protein complexes to mitochondrial function. Rat hearts were subjected to ischemia-reperfusion (I/R) with or without 1nM Bendavia perfusion beginning at the onset of reperfusion. The native expression of mitochondrial Complexes III and V were significantly reduced after I/R, and were restored with Bendavia (see Figure). The appearance of degradation bands was also noted in hearts after I/R, and these products of protein complex breakdown were also significantly reduced with Bendavia treatment. Respirometry studies in permeabilized ventricular fibers showed lower Complex I-dependent respiration after I/R (208±19 v 42±9 pmol O2/mg*s) in control v I/R, respectively; P
1030. Engineering Cytosine Deaminase for Suicide Gene Therapy
Authors: Margaret E. Black, Sheri D. Mahan, Greg C. Ireton, Catherine Knoeber, Barry L. Stoddard
Journal: Molecular Therapy (2004)

Cytosine deaminase (CD) is currently being used as a suicide gene for cancer gene therapy. The premise of this therapy is the preferential deamination of 5-fluorocytosine (5FC) to 5-flurorouracil by cancer cells expressing cytosine deaminase. However, a lack of efficient gene transfer to tumors combined with inefficient 5FC turnover currently limits the clinical applications of this gene therapy approach. As a means to address this problem, we have used protein engineering to 1) create novel cytosine deaminases that confer increased 5FC sensitivity to cells that express these variants and 2) investigate the role of residues that line the active site pocket with respect to substrate utilization.
An in vivo to in vitro pipeline for receptor oncogene discovery and validation
Authors: Yi Fang Lee, Nur Lina Mohamed Salleh, Kartiki Desai, Lance Miller
Journal: Clinical Cancer Research (2007)

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

C64 

Extracellular receptors and/or secreted growth factors that drive cancer metastasis make provocative targets for immunotherapy. Humanized antibodies designed against HER2/neu (Herceptin) and EGFR (Erbitux), are examples of potent receptor-targeted immunotherapies widely used for treating late-stage breast and colorectal cancers, respectively. To discover novel candidate receptor/secreted oncogenes, we used a whole-genome data-mining approach that takes advantage of large microarray studies of breast tumors annotated for clinical outcomes. First, the Gene Ontology database (www.geneontology.org) was used to identify all genes encoding known and predicted transmembrane receptors and secreted factors represented on the Affymetrix U133A and U133B genechips (~33,000 well annotated genes). The expression patterns of these genes across breast tumors were then correlated by Cox proportional-hazards regression to the distant metastasis-free survival of patients among 5 independent breast cancer cohorts. Of the resultant 25 genes significantly associated with cancer recurrence in multiple cohorts, a number of known or suspected oncogenes were observed including VEGF-A, TMPRSS4, IGFBP5, HPSE and ARTN. Several receptors without previous implication in breast cancer were identified and further investigated: Phosphatidylserine receptor (PTDSR), G-protein coupled receptor 56 (GPR56) and Histamine receptor 2 (HRH2). These receptors were functionally assessed in vitro for oncogenic and metastatic properties such as proliferation, motility, invasiveness and anchorage independent growth. Preliminary findings showed that siRNA knock-down of each of the three receptors (individually) led to a significant alteration in both cell proliferation and anchorage-independent growth in breast cancer cell lines with high endogenous expression. Though preliminary, these early results suggest that the extrapolation of gene-survival associations in human primary tumors holds promise in identifying functionally relevant cancer targets.
Repeat endocarditis: analysis of risk factors based on the International Collaboration on Endocarditis – Prospective Cohort Study
Authors: L. Alagna, L.P. Park, B.P. Nicholson, A.J. Keiger, J. Strahilevitz, A. Morris, D. Wray, D. Gordon, F. Delahaye, J. Edathodu, J.M. Miró, N. Fernández-Hidalgo, F.M. Nacinovich, R. Shahid, C.W. Woods, M.J. Joyce, D.J. Sexton, V.H. Chu
Journal: Clinical Microbiology and Infection (2013)
720. Tolerisation of Mice To Allow Repeated Administration of Recombinant Sendai Virus Vector to the Airways
Authors: Uta Griesenbach, Rosemary Boyton, Luci Somerton, Sara Escudero Garcia, Stefano Ferrari, Toshiyuki Owaki, Shu Tsugumine, Duncan M. Geddes, Mamoru Hasegawa, Danny Altmann, Eric W. F. W. Alton
Journal: Molecular Therapy (2004)

Top of pageAbstract
Sendai virus (SeV) is currently the only viral vector that transfects airway epithelial cells efficiently in vivo. However, as for any other viral vector repeated administration, leads to a significant drop in gene expression. Induction of immunological tolerance may permit repeated administration of the SeV vector. To achieve this we investigated the induction of immunological tolerance to the CD4 and CD8 T cell immunodominant epitopes of SeV. These peptides (100 mg/mouse) or a control peptide were administered to the lungs of C57Bl/6 mice (female, 6–8 weeks) via “sniffing” 10 days before the first virus administration (dF/SeV-GFP 106 pfu/mouse). 21 days after the first virus administration, mice were repeatedly transfected with dF/SeV. To avoid interference from anti-GFP antibodies, the second transfection was carried out with dF/SeV-lacZ (107 pfu/mouse). Two days after dF/SeV-lacZ administration all animals were culled. The lungs were harvested for βgal quantification and T-cell proliferation in response to the immunodominant epitopes was assessed to determine immunological tolerance. In addition serum was collected to measure anti-SeV neutralising antibodies. Administration of peptide 1 or 2 and 1+2 reduced CD4 and CD8 T-cell proliferation ex vivo after re-challenge with the respective protein by >60%. βgal expression following a second administration of SeV in mice receiving no peptide or the control peptide was 40–50% lower compared to mice that only had a single administration. Administration of the peptides did not elevate expression levels over levels measured in these control groups. This result indicates either that T cell responses need to be further reduced or that immune mechanisms other than T cells play a major role in eliminating SeV.
PENICILLIN IN SUPPURATIVE DISEASE OF THE LUNGS DUE TO STREPTOCOCCUS HEMOLYTICUS
Authors: Harold J. F. Kullman, Jacob Antrim Crellin
Journal: Annals of Internal Medicine (1945)

Article1 August 1945PENICILLIN IN SUPPURATIVE DISEASE OF THE LUNGS DUE TO STREPTOCOCCUS HEMOLYTICUSHAROLD J. F. KULLMAN, JACOB ANTRIM CRELLINHAROLD J. F. KULLMANSearch for more papers by this author, JACOB ANTRIM CRELLINSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-23-2-135 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSince penicillin has been employed clinically only since 1941 and, until comparatively recently, has not been available in sufficient quantity to permit the study of a large series of cases, the amount of literature concerning its clinical use in suppurative diseases of the lungs is necessarily limited. There is now sufficient evidence, however, to justify its employment in pneumonia, suppurative pneumonitis, lung abscess and empyema when due to an organism or organisms susceptible to the antibiotic action of penicillin.Although a definite decrease of empyema has occurred since the use of the sulfonamides, there is a limited group of sulfonamide...Bibliography1. FLEMINGFLOREYBODENHAMCUTLERHUDSONCHRISTIEJEFFREYFLOREYROBINSON AHWDCECRVRVJBMEJN: Discussion on penicillin, Proc. Roy. Soc. Med., 1944, xxxvii, 101-112. Google Scholar2. RAMMELKAMPKEEFER CHCS: The absorption, excretion and toxicity of penicillin administered by intrathecal injection, Am. Jr. Med. Sci., 1943, ccv, 342-350. CrossrefGoogle Scholar3. TILLETTCAMBIERMCCORMACK WSMJJE: The treatment of lobar pneumonia and pneumococcal empyema with penicillin, Bull. New York Acad. Med., 1944, xx, 142-178. Google Scholar4. BLAKECRAIGE FGB: Penicillin in suppurative disease of the lungs, a report of 3 cases, Yale Jr. Biol. and Med., 1943, xv, 507-516. Google Scholar5. BENNETTPARKES IT: Penicillin in sulfonamide-resistant pneumonias: with special reference to staphylococcal infection and empyema, Lancet, 1944, i, 305-306. CrossrefGoogle Scholar6. Case Records of Massachusetts General Hospital, Case No. 30031, New England Jr. Med., 1944, ccxxx, 82-87. Google Scholar7. MALLORY TB: Case Records of Massachusetts General Hospital, Case No. 29162, New England Jr. Med., 1943, ccxxviii, 519-522. Google Scholar8. MELENEY FL: The difficulty in evaluating drug treatment in surgical infections, Jr. Am. Med. Assoc., 1944, cxxiv, 1021-1026. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Received for publication November 20, 1944. Nextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1945Volume 23, Issue 2Page: 135-146KeywordsAbscessesLungsPenicillinPneumoniaPneumonitisStreptococcusSulfonamide ePublished: 1 December 2008 Issue Published: 1 August 1945 Copyright & PermissionsCopyright, 1945, by The American College of PhysiciansPDF downloadLoading ...