tbuckley/cabot-search huggingface dataset:
PTH-034 Stress-induced immunomodulation in irritable bowel syndrome suppresses Th1 and Th2 cytokines
Authors: D C Bullas, D Bulmer, N Arebi, G E Dukes, S Gurmany, L Kruidenier, K J Hicks, W S Atkin, M A Kamm, A R Hobson
Journal: Gut (2010)

<h3>Introduction</h3> Stress induced immunomodulation has evolved to confer maximum biological advantage to an organism exposed to varying environmental stressors. Stress is also implicated in the aetiology of Irritable Bowel Syndrome (IBS). Herein, we examined the immunophenotype of IBS patients for evidence of stress related immunomodulation. <h3>Methods</h3> 24-IBS patients and 9-matched controls subjects were studied. Comprehensive clinical, psychological (eg, somatisation) and symptomatic (eg, Visceral Sensitivity Index (VSI)) evaluations were performed. Peripheral blood mononuclear cells (PBMC9s) were stimulated using lipopolysacharide (5-concentrations) in the presence or absence of exogenous corticotrophin releasing hormone (CRH). A broad panel of inflammatory markers were measured in the supernatant. A one-way ANOVA was performed and data reported as point estimates of difference, 95% CI (IBS-Controls). <h3>Results</h3> Levels of IL2 (−44.5 (−66 to −22) p&lt;0.001), IL4 (−32.5 (−54 to −11) p=0.0004), IL5 (−15.3 (−21 to 8.9) p&lt;0.001), IL10 (−1088 (685 to 1491) p&lt;0.001), IL13 (−60.3 (−85 to −36) p&lt;0.001), TNFα (−5452 (−3577 to −7327) p&lt;0.001), and IFNγ (−1353 (−471 to −2235) p=0.002) were lower in IBS compared to controls and negatively correlated with measures of symptom severity (eg, IL-5 and Verbal Descriptor Visual Analogue Scale for symptom intensity (VDVAS-I) r=−0.65, p&lt;0.001) and psychological comorbidity (eg, IL-5 and somatisation, r=−0.41, p=0.02). In contrast, IL6 (8431 (13 160 to 3703) p&lt;0.001) and IL8 (14 186 (17 934 to 10 437) p&lt;0.001) levels were higher in IBS and positively correlated with measures of symptom severity (eg, IL-8 and VDVAS-I, r=0.61, p&lt;0.001) and psychological comorbidity (eg, IL-8 and somatisation, r=0.37, p=0.03). Co-incubation with CRH suppressed IFNγ levels in control subjects to the same level as IBS patients (254.1 (−491 to 999) p=0.05). <h3>Conclusion</h3> As seen in chronic stress, IBS patients suppress Th1 and Th2 cytokine release from stimulated PBMC9s and this suppression is negatively correlated with increasing symptom severity and psychological comorbidity. Elevation of IL-6, and suppression of IFN-γ, IL-2 and IL-4 may indicate a shift towards a TH17 immune profile. This immunophenotype would convey a biological advantage in terms of enhanced mucosal host defence but may also establish a pro-inflammatory mucosal cytokine profile which would promote gastrointestinal symptoms. The potential interaction between stress and TH17 immune function in IBS could represent a new insight in IBS pathophysiology.
Personalized Oncology Meets Immunology: The Path toward Precision Immunotherapy
Authors: Rajarsi Mandal, Timothy A. Chan
Journal: Cancer Discovery (2016)

Personalized oncology aims to tailor therapy by targeting the unique genetic characteristics of a patient's tumor, whereas cancer immunotherapy focuses on activating the patient's immune system to control the tumor. The fusion of these ostensibly separate strategies has created a new dimension for personalized cancer immunotherapy. This entails the development of next-generation cancer vaccines that target neoantigens as well as the use of mutational signatures as predictive biomarkers for clinical response. The optimal use of immunotherapeutic agents will hinge on a robust understanding of the mutational profile of a cancer's genome that significantly dictates antitumor immunity and immunotherapeutic response.Cancer immunotherapy has provided substantial clinical benefit in a significant number of patients with advanced disease. However, the need for more precise immunotherapies and predictive biomarkers remains pressing. Recent progress in these areas has been promising and has created a framework for precision immune-oncology. Cancer Discov; 6(7); 703-13. ©2016 AACR.
A Controlled Trial of Antimicrobial Prophylaxis for Lyme Disease after Deer-Tick Bites
Authors: Eugene D. Shapiro, Michael A. Gerber, Nancy B. Holabird, Anne T. Berg, Henry M. Feder, Gillian L. Bell, Paul N. Rys, David H. Persing
Journal: New England Journal of Medicine (1992)

Borrelia burgdorferi, which causes Lyme disease, is transmitted by deer ticks (Ixodes dammini) in the northeastern and midwestern United States. Although deer-tick bites are common in areas in which the disease is endemic, there is uncertainty about how to manage the care of persons who are bitten.
Antagonism of Dicumarol by Vitamin K Preparations
Authors: R. Miller, W. Proctor Harvey, Clement A. Finch
Journal: New England Journal of Medicine (1950)

DICUMAROL is of proved value in the prophylaxis and treatment of thromboembolic disease. In recent years it has come into general clinical usage. The narrow margin between a clinically effective prothrombin level and the prothrombin level at which bleeding occurs imposes a certain hazard in treatment. Even with the most careful management of Dicumarol therapy, an unsuspected complication such as an asymptomatic peptic ulcer may result in fatal hemorrhage. The literature attests the seriousness of such bleeding in patients treated with Dicumarol.1 2 3 4In event of hemorrhage it is of the utmost importance to remedy quickly the coagulation defect produced by . . .
Quantitation of Tumor Antigen Expression on the Surface of Malignant Line I&lt;sub&gt;b&lt;/sub&gt; Lymphocytes by Immuno-electron Microscopy&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;, &lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: R E Morris, D M Bentley, G M Ciraolo
Journal: JNCI Journal of the National Cancer Institute (1981)

Malignant line Ib lymphocytes obtained from strain C58/J mice moribund with the syngeneic, transplantable leukemia were examined by transmission electron microscopy. A large, multilobulated nucleus containing a prominent nucleolus was typically viewed. In addition to normal organelles, cytoplasmic elements included frequent intracisternal A-type virions. The cell membrane possessed pseudopodia, and occasionally C-type viruses were noted budding from the plasma membrane. On the basis of complement-mediated antibody cytotoxicity assays with the use of either antiserum against mouse IgM, antiserum against mouse IgG, or antiserum against Thy 1.2 antigen, Ib cells were characterized as T-cells. Similarly, leukemia lymphocytes were lysed by a highly specific rabbit anti-Ib tumor-associated surface antigen (TASA) in the presence of complement. The density and distribution of TASA on malignant lymphocytes were analyzed by immuno-electron microscopy with the use of a bridging technique in conjunction with antiserum against Ib TASA. The following observations were reported after the examination of more than 100 randomly selected Ib lymphocytes: a) The density of the TASA was low, b) the distribution of the TASA was random, and c) no evidence indicated cell cycle-dependent expression of the TASA.
Facial Palsy in Lyme Disease
Authors: Eric R. Eggenberger
Journal: New England Journal of Medicine (1993)

To the Editor: In Images in Clinical Medicine, Klempner and Molloy (Dec. 17 issue)1 showed a young man with Lyme disease who had erythema chronicum migrans and “Bell's palsy.” The term “Bell's palsy,” from the Scottish anatomist and surgeon,2 is reserved for an idiopathic lower-motor-nerve lesion (“peripheral”) of the seventh cranial nerve3. Lower-motor-nerve facial palsies are a common manifestation of Lyme disease, with a presumed pathophysiology intimately related to the infection itself; therefore, the use of “Bell's palsy” in this setting is incorrect. Rather, this manifestation should merely be referred to as a lower-motor facial paresis associated with Lyme . . .
Orchitis, Parotitis and Meningoencephalitis Due to Lymphocytic-Choriomeningitis Virus
Authors: John M. Lewis, John P. Utz
Journal: New England Journal of Medicine (1961)

SINCE Wallgren's1 original description of aseptic meningitis a large number of diverse etiologic agents have been associated with this syndrome. When the meningitis has been accompanied by parotitis and orchitis the likeliest cause has been mumps, whether or not viral diagnostic studies have been performed. With the wider use of laboratory methods, however, Coxsackie and ECHO viruses have been associated with cases showing either orchitis2 , 3 or parotitis4 , 5 although in none of these reports were all three manifestations seen in a single patient. The purpose of this communication is to report this clinical triad in a patient infected with the lymphocytic-choriomeningitis . . .
Intracellular Magnesium Depletion in Chronic Renal Failure
Authors: Pin Lim, Stella Dong, Oon Teik Khoo
Journal: New England Journal of Medicine (1969)

Skeletal-muscle magnesium, estimated as an index of body magnesium store, was significantly lower (p less than 0.05) in 12 patients with advanced chronic renal failure (most of whom showed hypermagnesemia) than in controls matched for sex and age. There is indirect evidence that renal insufficiency sets at a new level the control of magnesium gradient across the cell membrane. Depletion of total-body (intracellular) magnesium was probably due to inadequate intake, as supplied by the modified Giovannetti diet, and impaired absorption, exacerbated by frequent vomiting. Peritoneal dialysis did not contribute greatly to magnesium depletion in the patients. Two patients had clinical features of hypermagnesemia (lethargy, drowsiness, depressed tendon jerks, general flaccidity, relative hypotension and prolonged PR intervals, QRS complexes and QT segments on the electrocardiogram), but no patient had features of magnesium depletion.
Seventy-Five Years of Public Health in Massachusetts
Authors: Merrill E. Champion
Journal: New England Journal of Medicine (1945)

THE seventy-fifth anniversary of the founding of the State Board of Health of Massachusetts calls to mind certain outstanding personalities and their relation to the development of public-health theory and practice in the Commonwealth. Most of these — though not all — were medical men; some of them were distinguished as well in fields other than that of public health. It is the purpose of this article to trace the origin and development of the public-health movement in Massachusetts and to discuss the part played by outstanding men who guided it through the years since 1869.Lemuel Shattuck, PioneerThe . . .
Immunoglobulin Response in Serum and Secretions after Immunization with Live and Inactivated Poliovaccine and Natural Infection
Authors: Pearay L. Ogra, David T. Karzon, Fay Righthand, Margaret MacGillivray
Journal: New England Journal of Medicine (1968)

The responses of the major immunoglobulins (gamma G, gamma M and gamma A) in serum and nasal and duodenal secretions were studied in infants and children after immunization with live and inactivated poliovaccines and after natural poliomyelitis infection. The serum immunoglobulin responses to these procedures resembled each other although higher levels followed the natural infection. After immunization with live attenuated vaccine, antibody activity was found regularly in nasal and duodenal secretory gamma A immunoglobulin, but not after immunization with inactivated vaccine. To explain the alimentary immunity that follows infection with attenuated or wild poliovirus, it is proposed that orally administered live virus, which implants and replicates in the pharynx and intestinal tract, stimulates local lymphoid cells, leading to the production of immunoglobulins predominantly of the gamma A class.
Abstract POSTER-TECH-1130: Identification of putative genes involved in early steps of epithelial ovarian cancer pathogenesis
Authors: Yahya Tamimi, Ikram Burney, Moza Al-Kalbani, Ritu Lakhtari, Roseline Godbout, Mansour Al-Moundhri
Journal: Clinical Cancer Research (2015)

Abstract Epithelial ovarian cancer (EOC) is a deadly q disease and the related statistics are alarming with 15000 lives claimed in USA each year. EOC is a subtle disease since the majority of patients at presentation are diagnosed with a higher stage disease characterized by an aggressive potential. Early diagnosis seems to be of importance since complete cure can reach up to 90% if the disease is diagnosed at an early stage. Therefore, biological markers to detect patients at an early stage of the disease progression are urgently needed. In this study, the focus was centered on the transcription factor E2F5 used as biomarker and highly expressed at early stages of EOC pathogenesis. Therefore, we hypothesize that downstream genes regulated by this transcription factor might be also involved in the early events leading to ovarian cancer and can therefore potentially serve as useful biomarkers. Chromatin Immuno-Precipitation (ChIP) was performed using two ovarian cancer cell lines SK-OV-3 and OVCAR-3 and an antibody against E2F5 transcription factor. The enriched chromatin was cloned and sequenced before using available databases for BLAST and identification of downstream regulated genes. A short list of relevant genes, all involved in cancer, was obtained and analysis for their putative role in early detection of EOC is ongoing. The selected genes will be also validated using frozen human ovarian tissues available in our institution. ChIP is a robust technology to identify genes regulated by E2F5 with a putative potential to play a crucial role in the early steps of ovarian cancer pathogenesis. Citation Format: Yahya Tamimi, Ikram Burney, Moza Al-Kalbani, Ritu Lakhtari, Roseline Godbout, Mansour Al-Moundhri. Identification of putative genes involved in early steps of epithelial ovarian cancer pathogenesis [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-TECH-1130.
Abstract 15457: The -765G>C Polymorphism in the Gene Encoding for Cyclooxygenase-2 Increases the Risk for Atherothrombotic Events in Patients with Coronary Artery Disease: A Prospective One-Year Follow-Up Study
Authors: Jeroen Jaspers Focks, Thomas O Bergmeijer, Marc A Brouwer, Nick Clappers, Martijn G van Oijen, Rene H te Morsche, Christian M Hackeng, Wilbert H Peters, Jurrien M ten Berg, Freek W Verheugt
Journal: Circulation (2012)

Background A single nucleotide polymorphism (SNP) known as -765G>C is known to reduce the expression of cyclooxygenase-2 (COX-2). With regard to the effect of this SNP on cardiovascular risk, contr...
Treatment of Hypertension with Benzydroflumethiazide as the Sole Antihypertensive Agent
Authors: Richard W. P. Achor, Kenneth G. Berge, Ray W. Gifford, Harold L. Mason
Journal: New England Journal of Medicine (1961)

BENZOTHIADIAZINE diuretics have become increasingly important in the treatment of arterial hypertension since the introduction of chlorothiazide in 1957.1 , 2 Although chlorothiazide is effective and possesses relatively few toxic effects, much effort has been made to improve on this parent compound. Such endeavor has led to the synthesis of the dihydro derivative of chlorothiazide (hydrochlorothiazide), which is at least ten times as potent as chlorothiazide on a milligram basis.3 , 4 In addition, fluorine-containing homologues of both drugs that appear to be similar in effectiveness and potency have been developed.3 , 5 A major difficulty in the use of these benzothiadiazine diuretics has been their . . .
A Nationally Representative Study of Calcific Uremic Arteriolopathy Risk Factors
Authors: Sagar U. Nigwekar, Sophia Zhao, Julia Wenger, Jeffrey L. Hymes, Franklin W. Maddux, Ravi I. Thadhani, Kevin E. Chan
Journal: Journal of the American Society of Nephrology (2016)

Accurate identification of risk factors for calcific uremic arteriolopathy (CUA) is necessary to develop preventive strategies for this morbid disease. We investigated whether baseline factors recorded at hemodialysis initiation would identify patients at risk for future CUA in a matched case-control study using data from a large dialysis organization. Hemodialysis patients with newly diagnosed CUA ( n =1030) between January 1, 2010, and December 31, 2014, were matched by age, sex, and race in a 1:2 ratio to hemodialysis patients without CUA ( n =2060). Mean ages for patients and controls were 54 and 55 years, respectively; 67% of participants were women and 49% were white. Median duration between hemodialysis initiation and subsequent CUA development was 925 days (interquartile range, 273–2185 days). In multivariable conditional logistic regression analyses, diabetes mellitus; higher body mass index; higher levels of serum calcium, phosphorous, and parathyroid hormone; and nutritional vitamin D, cinacalcet, and warfarin treatments were associated with increased odds of subsequent CUA development. Compared with patients with diabetes receiving no insulin injections, those receiving insulin injections had a dose-response increase in the odds of CUA involving lower abdomen and/or upper thigh areas (odds ratio, 1.49; 95% confidence interval, 1.03 to 2.51 for one or two injections per day; odds ratio, 1.88; 95% confidence interval, 1.30 to 3.43 for 3 injections per day; odds ratio, 3.74; 95% confidence interval, 2.28 to 6.25 for more than three injections per day), suggesting a dose-effect relationship between recurrent skin trauma and CUA risk. The presence of risk factors months to years before CUA development observed in this study will direct the design of preventive strategies and inform CUA pathobiology.
Cost Analysis of the American Board of Internal Medicine's Maintenance-of-Certification Program
Authors: Lonnie Hanauer
Journal: Annals of Internal Medicine (2016)

Letters19 April 2016Cost Analysis of the American Board of Internal Medicine's Maintenance-of-Certification ProgramLonnie Hanauer, MDLonnie Hanauer, MDFrom West Orange, New Jersey.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L16-0005 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read Sandhu and colleagues' cost analysis on ABIM's MOC program with interest (1). I first took the internal medicine boards 50 years ago (actually 48) when the ABIM gave a written examination followed months later by an oral examination for those who had passed the written. I “failed to pass” the oral examination and had to wait a year before I could make another attempt. Rumbling was increasing about the lack of validity of the oral examination. A few years later, ABIM announced that it would give a select few candidates the written and oral examinations ...Reference1. Sandhu AT, Dudley RA, Kazi DS. A cost analysis of the American Board of Internal Medicine's Maintenance-of-Certification program. Ann Intern Med. 2015;163:401-8. [PMID: 26216046]. doi:10.7326/M15-1011 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From West Orange, New Jersey.Disclosures: Author has disclosed no conflicts of interest. Form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterest Forms.do?msNum=L16-0005. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoA Cost Analysis of the American Board of Internal Medicine's Maintenance-of-Certification Program Alexander T. Sandhu , R. Adams Dudley , and Dhruv S. Kazi Cost Analysis of the American Board of Internal Medicine's Maintenance-of-Certification Program Christopher D. Adams Cost Analysis of the American Board of Internal Medicine's Maintenance-of-Certification Program Alexander T. Sandhu , R. Adams Dudley , and Dhruv S. Kazi Metrics 19 April 2016Volume 164, Issue 8Page: 571KeywordsConflicts of interestDisclosureOral medicine ePublished: 19 April 2016 Issue Published: 19 April 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The Use of<i>Rauwolif serpentina</i>in Hypertensive Patients
Authors: Robert W. Wilkins, Walter E. Judson
Journal: New England Journal of Medicine (1953)

RAUWOLFIA serpentina (Ophioxylon serpentinum) has been used in India for many years to treat a variety of diseases that at first thought appear to bear little similarity to one another. These include insanity, epilepsy, insomnia, hysteria, eclampsia and hypertension. On reflection, however, these various diseases could have a common denominator if they were all relieved symptomatically by a sedative or a "relaxing" drug such as Rauwolfia. Our attention was drawn to the drug because reports of its hypotensive effects seemed to be fairly well documented; indeed, the conservative claims made for it by several authors increased rather than . . .
Rare variant alleles in the light of the neutral theory.
Authors: M Kimura
Journal: Molecular Biology and Evolution (1984)

Based on the neutral theory of molecular evolution and polymorphism, and particularly assuming "the model of infinite alleles," a method is proposed which enables us to estimate the fraction of selectively neutral alleles (denoted by Pneut) among newly arisen mutations. It makes use of data on the distribution of rare variant alleles in large samples together with information on the average heterozygosity. The formula proposed is Pneut = [He/(1-He)] [loge(2nq)/n alpha (x less than q)], where n alpha(x less than q) is the average number of rare alleles per locus whose frequency, x, is less than q; n is the average sample size used to count rare alleles; He is the average heterozygosity per locus; and q is a small preassigned number such as q = 0.01. The method was applied to observations on enzyme and other protein loci in plaice, humans (European and Amerindian), Japanese monkeys, and fruit flies. Estimates obtained for them range from 0.064 to 0.21 with the mean and standard error Pneut = 0.14 +/- 0.06. It was pointed out that these estimates are consistent with the corresponding estimate Pneut(Hb) = 0.14 obtained independently based on the neutral theory and using data on the evolutionary rate of nucleotide substitutions in globin pseudogenes together with those in the normal globins.
Guiding Lay Navigation in Geriatric Patients With Cancer Using a Distress Assessment Tool
Authors: Gabrielle B Rocque, Richard A Taylor, Aras Acemgil, Xuelin Li, Maria Pisu, Kelly Kenzik, Bradford E Jackson, Karina I Halilova, Wendy Demark-Wahnefried, Karen Meneses, Yufeng Li, Michelle Y Martin, Carol Chambless, Nedra Lisovicz, Mona Fouad, Edward E Partridge, Elizabeth A Kvale
Journal: Journal of the National Comprehensive Cancer Network (2016)

There is growing interest in psychosocial care and evaluating distress in patients with cancer. As of 2015, the Commission on Cancer requires cancer centers to screen patients for distress, but the optimal approach to implementation remains unclear.We assessed the feasibility and impact of using distress assessments to frame lay navigator interactions with geriatric patients with cancer who were enrolled in navigation between January 1, 2014, and December 31, 2014.Of the 5,121 patients enrolled in our lay patient navigation program, 4,520 (88%) completed at least one assessment using a standardized distress tool (DT). Navigators used the tool to structure both formal and informal distress assessments. Of all patients, 24% reported distress scores of 4 or greater and 5.5% reported distress scores of 8 or greater. The most common sources of distress at initial assessment were pain, balance/mobility difficulties, and fatigue. Minority patients reported similar sources of distress as the overall program population, with increased relative distress related to logistical issues, such as transportation and financial/insurance questions. Patients were more likely to ask for help with questions about insurance/financial needs (79%), transportation (76%), and knowledge deficits about diet/nutrition (76%) and diagnosis (66%) when these items contributed to distress.Lay navigators were able to routinely screen for patient distress at a high degree of penetration using a structured distress assessment.