tbuckley/cabot-search huggingface dataset:
High Prevalence of Viral Infection in Adults with Homozygous and Heterozygous Alpha<sub>1</sub>-Antitrypsin Deficiency and Chronic Liver Disease
Authors: Theresa Propst, Albert Propst, Otto Dietze, Gert Judmaier, Herbert Braunsteiner, Wolfgang Vogel
Journal: Annals of Internal Medicine (1992)

To determine the prevalence of chronic liver disease in adults with homozygous (Pi ZZ) and heterozygous (Pi Z) alpha 1-antitrypsin deficiency and to assess the presence of other possible risk factors for the development of chronic active hepatitis and cirrhosis of the liver in these patients.Cross-sectional study.A referral-based university hospital.Consecutive patients (164) with the Pi ZZ and Pi Z phenotype with and without chronic liver disease.The presence of antibody to hepatitis C virus (anti-HCV) was determined using an assay incorporating synthetic peptide antigen from capsid protein (United Biomedical [UBI] assay) and a second-generation enzyme immunoassay (Abbott test); the presence of antibody to hepatitis B virus (anti-HBV) was determined using radioimmunoassays incorporating hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg); assays for antinuclear antibody and antimitochondrial antibody (M2 subtype) were also done, and alcohol abuse was assessed by history.Among patients with cirrhosis (32%), 62% were anti-HCV positive by the Abbott test (P = 0.006), and 41% were anti-HCV positive by the UBI assay (P = 0.007). Thirty-three percent of patients with cirrhosis had hepatitis B virus (HBV) infection (P = 0.01); 41% had a history of alcoholism; and 12% had features of autoimmune liver disease. Only five patients (9%) with cirrhosis had no other risk factor for chronic liver disease. Among patients with chronic active hepatitis (7%), 80% were anti-HCV positive by the Abbott test (P = 0.002), and 75% were anti-HCV positive by the UBI assay (P less than 0.001). Thirty percent of patients with chronic active hepatitis had HBV infection (P = 0.023); 18% had autoimmune hepatitis; and 8% abused alcohol. Only two patients (17%) had no additional risk factor for the development of chronic active hepatitis. Among patients with steatosis of the liver (48%), 5% were anti-HCV positive by the Abbott test, and none were anti-HCV positive by the UBI assay; 18% had serologic evidence of past HBV infection, and 28% abused alcohol. Among patients without chronic liver disease (13%), no viral infection could be found; 9% were alcoholics.Chronic liver disease in patients with alpha 1-antitrypsin deficiency is associated with a high prevalence of viral infection; this infection, rather than alpha 1-antitrypsin deficiency alone, may be the cause of the liver disease in such patients.
Is central obesity associated with cirrhosis-related death or hospitalization? A population-based, cohort study
Authors: George N. Ioannou, Noel S. Weiss, Edward J. Boyko, Kris V. Kowdley, Steven E. Kahn, Robert L. Carithers, Elaine C. Tsai, Jason A. Dominitz
Journal: Clinical Gastroenterology and Hepatology (2005)
Urinary cysteinyl leukotriene E<sub>4</sub> significantly increases during pain in children and adults with sickle cell disease
Authors: Joshua J. Field, Robert C. Strunk, Jessica E. Knight‐Perry, Morey A. Blinder, R. Reid Townsend, Michael R. DeBaun
Journal: American Journal of Hematology (2009)

Abstract Baseline level of the cysteinyl leukotriene (CysLT), leukotriene E 4 (LTE 4 ), is associated with an increased pain rate in children and adults with sickle cell disease (SCD). To provide additional evidence for a role of CysLTs in the pathogenesis of vaso‐occlusion, we tested the hypothesis that LTE 4 levels will increase within an individual during painful episodes compared to baseline. In a cohort of 19 children and adults with SCD, median LTE 4 levels increased from 82.36 pg/mg creatinine at baseline to 162.81 pg/mg creatinine during a painful episode ( P &lt; 0.001). These data further support a contribution of CysLTs to the process of vaso‐occlusion. Am. J. Hematol., 2009. © 2009 Wiley‐Liss, Inc.
Abstract 4448: Overexpression of ECT2 promotes proliferation and metastasis of UPSC
Authors: Claire M. Mach, Thomas J. Magliaro, Matthew L. Anderson
Journal: Cancer Research (2014)

Abstract Introduction: UPSC is a rare but aggressive malignancy that accounts for no more than 5 to 10% of uterine cancers, but more than 40% of associated uterine cancer deaths. The molecular events responsible for the poor clinical outcomes observed with UPSC are largely unknown. Epithelial cell transforming sequence 2 oncogene (ECT2) is a guanine nucleotide exchange factor (Rho-GEF) that catalyzes the exchange of GDP for GTP by Rho family GTPases. High levels of ECT2 expression have been reported in brain, lung and breast cancers, where they were shown promote metastasis. However, the role of ECT2 in UPSC has not been previously explored. Methods: After obtaining IRB permission, ECT2 mRNA and protein expression were measured in flash frozen specimens of normal proliferative endometrium (n=8) and UPSC (n =8) by quantitative real-time PCR (qPCR) and Western blot. Established cultures of UPSC cell lines (UPSC-ARK1, UPSC-ARK2) were transfected with either an siRNA targeting ECT2 or a non-targeting control (Dharmacon) using Lipofectamine 2000 (Invitrogen). Reduced expression of ECT2 following transfections with ECT2 siRNAs was confirmed by qPCR and Western blot. Standard MTS and Caspase 3/7 assays (Promega) were utilized to measure proliferation and apoptosis. Colony formation and Boyden chamber assays were used to measure metastatic capacity, migration and invasion in vitro. Results: Our data indicate that ECT2 is overexpressed &amp;gt;4-fold in nearly all UPSC specimens tested (n=8, p&amp;lt;0.001). We also found that ECT2 is robustly expressed in both the UPSC-ARK1 and UPSC-ARK2 cell lines. Utilizing these 2 cell lines, we found that knockdown of ECT2 significantly decreased proliferation (UPSC-ARK1: 0.62-fold versus control; n=3, p&amp;lt;0.05; UPSC-ARK2: 0.34-fold versus control, p&amp;lt;0.05) and increased rates of apoptosis (UPSC-ARK1: 1.3-fold; n=3, p&amp;lt;0.05; UPSC-ARK2: 2.2-fold, n=3, p&amp;lt;0.05) in both cell lines tested. Decreased ECT2 expression targeted by transfection with siRNAs led to decreased rates of colony formation in UPSC-ARK1 and UPSC-ARK2 cell lines. Knockdown of ECT2 also significantly reduced rates of migration and invasion observed in vitro with both cell lines. Conclusions: Overexpression of ECT2 plays a critical role in promoting the growth and metastasis of UPSC. Targeting ECT2 expression may provide an effective strategy for improving outcomes for UPSC and other human cancers where hyperactivation of metastasis-promoting Rho GTPases are observed. Citation Format: Claire M. Mach, Thomas J. Magliaro, Matthew L. Anderson. Overexpression of ECT2 promotes proliferation and metastasis of UPSC. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4448. doi:10.1158/1538-7445.AM2014-4448
The Doctor I Want to Be
Authors: Tamara Bockow
Journal: Annals of Internal Medicine (2011)

On Being a Doctor16 August 2011The Doctor I Want to BeTamara Bockow, BSTamara Bockow, BSFrom University of Pennsylvania Medical School, Philadelphia, PA 19104-6056.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-155-4-201108160-00015 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail He spiked a fever of 102.3 last night. His brain MRI is unremarkable, his CSF cell counts are inconclusive, and his urine culture is negative.”I reported these perplexing findings to my attending physician on morning rounds, pondering the next step in this patient's treatment. As a third-year medical student on my medicine rotation, I was eager to begin learning the art of differential diagnosis and medical management. However, during my time on the wards, I learned not only what it takes to be great doctor but what it means to be a healer.Mr. Mitchell was an 83-year-old man ... Author, Article, and Disclosure InformationAffiliations: From University of Pennsylvania Medical School, Philadelphia, PA 19104-6056.Corresponding Author: Tamara Bockow, BS, University of Pennsylvania Medical School, Philadelphia, PA 19104-6056; e-mail, [email protected]med.upenn.edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 16 August 2011Volume 155, Issue 4Page: 273KeywordsDementiaMeningitisPatientsPneumoniaRacial and ethnic issuesRunningSarcoidosisSurgeryUrine ePublished: 16 August 2011 Issue Published: 16 August 2011 Copyright & PermissionsCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Constitutive kinase activation of the TEL-Syk fusion gene in myelodysplastic syndrome with t(9;12)(q22;p12)
Authors: Yoshie Kuno, Akihiro Abe, Nobuhiko Emi, Minako Iida, Toshiya Yokozawa, Masayuki Towatari, Mitsune Tanimoto, Hidehiko Saito
Journal: Blood (2001)
Immunologic Response to Tetanus Toxoid Inoculation in Patients with Hepatic Cirrhosis
Authors: G. R. Cherrick, Lillian Pothier, J-J. Dufour, Sheila Sherlock
Journal: New England Journal of Medicine (1959)

THERE is some evidence that certain forms of chronic liver disease may be initiated by antigen–antibody reactions within liver cells. A heterogenetic antibody that fixes complement with human liver and agglutinates sheep red cells has been demonstrated in the serum of some persons suffering from acute hepatitis.1 Conceivably, in such cases, the antibody could combine with antigen in situ in the liver cells and lead to further tissue damage after the infection had disappeared.2 , 3 Furthermore, a substance, presumably antibody, that fixes complement in the presence of human liver homogenate has been found in the serum of patients having acute viral . . .
Management of adult testicular germ cell tumours: summary of updated SIGN guideline
Authors: G. C. W. Howard, M. Nairn
Journal: BMJ (2011)

Testicular germ cell tumours are rare. In 2008, 203 new cases were diagnosed in Scotland,1 with a crude incidence of 8.1 cases per 100 000 of the male population.2 It is the 15th most common cancer among all men in Scotland1 and the most common cancer in younger adult men.3 It is one of the few curable solid cancers, even when it has metastasised, and has a crude overall five year survival rate in Scotland of 95.8%.1 Although the cure rate is high, the toxicity of treatment is substantial, resulting in treatment related deaths and long term adverse effects. Potential effects on employment and fertility are of particular importance in this age group. This article summarises the most recent recommendations from the Scottish Intercollegiate Guidelines Network (SIGN) on the management of adult testicular germ cell tumours,4 updating 1998 SIGN guidelines on this condition. SIGN recommendations are based on systematic reviews of best available evidence. The strength of the evidence is graded as A, B, C, or D (figure⇓), but the grading does not reflect the clinical importance of the recommendations. Recommended best practice ("good practice points"), based on the clinical experience of the Guideline Development Group, is also indicated (as GPP). Explanation of SIGN grades of recommendations ### Initial assessment and referral in primary care
PET plus CT was better than conventional methods for correctly upstaging early NSCLC
Authors: Klaus L. Irion
Journal: Annals of Internal Medicine (2009)

ACP Journal Club15 December 2009PET plus CT was better than conventional methods for correctly upstaging early NSCLCKlaus L. Irion, MD, PhD, FBCR, FRCRKlaus L. Irion, MD, PhD, FBCR, FRCRLiverpool Heart and Chest Hospital and, Royal Liverpool University Hospital, Liverpool, England, UK (K.L.I.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-151-12-200912150-02010 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationMaziak DE, Darling GE, Inculet RI, et al. Positron emission tomography in staging early lung cancer: a randomized trial. Ann Intern Med. 2009;151:221-8, W-48. https://pubmed.ncbi.nlm.nih.gov/19581636Clinical Impact RatingsHospitalists: Oncology: Pulmonology: References1 Alzahouri K, Lejeune C, Woronoff-Lemsi MC, et al. Cost-effectiveness analysis of strategies introducing FDG-PET into the mediastinal staging of non–small-cell lung cancer from the French healthcare system perspective. Clin Radiol. 2005;60:479-92. [PMID: 15767106] Google Scholar2 National Institute for Clinical Excellence. The diagnosis and treatment of lung cancer. 2005. http://guidance.nice.org.uk/CG24/Guidance/pdf/English (accessed 17 Jul 2006). Google Scholar Author, Article, and Disclosure InformationAffiliations: Liverpool Heart and Chest Hospital and, Royal Liverpool University Hospital, Liverpool, England, UK (K.L.I.)This article was published at Annals.org on 1 December 2009. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByIntegrating radiomics into clinical trial design 15 December 2009Volume 151, Issue 12Page: JC6-10KeywordsBiopsyBone imagingComputed axial tomographyLung and intrathoracic tumorsLungsPositron emission tomographySurgeryThoracotomyThorax ePublished: 15 December 2009 Issue Published: 15 December 2009 CopyrightCopyright © 2009 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Congenital Esophageal Stenosis
Authors: Lester L. Vargas, Richard C. Britton, Edmund N. Goodman
Journal: New England Journal of Medicine (1956)

CONGENITAL esophageal stenosis at the level of the cardia is an uncommon and poorly understood anomaly. Since the majority of these cases in infants respond satisfactorily to instrumental dilatation, the precise nature of the stricture is rarely determined. For this reason, an unusual case in which the obstruction was caused by an annular band of hypertrophic muscle is reported.Case ReportJ. R. (B.H. 190203), a seven-week-old female infant, was admitted to the Babies Hospital of the Columbia–Presbyterian Medical Center on July 6, 1954, because of vomiting since birth. Soon after delivery it was noted that she accumulated excessive amounts . . .
Abstract P3-14-09: Preclinical Safety and Activity of MM-302, a HER2-Targeted Liposomal Doxorubicin Designed To Have an Improved Safety and Efficacy Profile over Approved Anthracyclines
Authors: TJ Wickham, J Reynolds, DC Drummond, DB Kirpotin, J Lahdenranta, SC Leonard, E Geretti, H Lee, S Klinz, BS Hendriks, K Olivier, I Eckelhofer, JW Park, CC Benz, VM Moyo, C Niyikiza, UB. Nielsen
Journal: Cancer Research (2010)

Abstract Background: Anthracyclines have been an effective backbone of breast cancer therapies for decades. However, cardiotoxicity issues associated with free anthracyclines have limited their effective use in the clinic and ledto the exploration of anthracycline-free regimens, particularly with HER2- positive cancers that require treatment with another cardiotoxic agent, trastuzumab. While liposomal doxorubicin formulations have succeeded in reducing cardiotoxicity, they have failed to demonstrate clearcut efficacy advantages and can involve other toxicities. To address the safety and efficacy limitations of currently available anthracyclines, we have designed a new liposomal formulation, MM-302, that targets doxorubicin to HER2- overexpressing tumor cells. Antibody fragments that bind to HER2 without blocking HER2-mediated signaling are coupled to the outer surface of pegylated liposomal doxorubicin. MM-302 specifically binds and enters tumor cells overexpressing HER2 with minimal uptake into normal cells such as cardiomyocytes which express low levels of HER2. Materials and methods: MM-302, untargeted pegylated liposomal doxorubicin (PLD), and free doxorubicin were compared for their uptake into target and nontarget cells, pharmacokinetics, biodistribution, tumor microdistribution using FACS and confocal microscopy, and anti-tumor activity in BT-474 and NCI-N87 xenograft models. Results: Cellular uptake studies in tumor cell lines expressing various levels of HER2 demonstrate that MM-302 delivers significantly higher doxorubicin levels to HER2 over-expressing tumor cells compared to PLD as well as similar or higher levels than highly permeable free doxorubicin. However, in human cardiomyocytes, while free doxorubicin was again taken up at high levels, doxorubicin uptake was dramatically lower with both MM-302 and PLD. Pharmacokinetic studies in mice demonstrate that MM-302 has a similar half life, clearance, and organ distribution compared to PLD. In HER2-overexpressing BT-474 breast and NCI-N87 gastric tumor xenografts, MM-302 exhibits superior anti-tumor activity to both free anthracyclines and PLD. Tumor microdistribution studies further suggest that differences in the localization of doxorubicin in the tumor may be responsible for the enhanced activity of MM-302 compared to free doxorubicin and PLD. Discussion: These preclinical data suggest that MM-302 may provide in clinical practice a new opportunity to specifically deliver an anthracycline to HER2-overexpressing tumors with a potentially cleaner safety profile and improved efficacy over currently available free or liposomal doxorubicin. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-14-09.
Idiotypic sensitization in utero of children born to mothers with schistosomiasis or Chagas' disease.
Authors: S M Eloi-Santos, E Novato-Silva, V M Maselli, G Gazzinelli, D G Colley, R Correa-Oliveira
Journal: Journal of Clinical Investigation (1989)

Cord blood mononuclear cells (CBMC) of neonates born of mothers with Chagas' disease or schistosomiasis exhibited strong proliferative responses against idiotypes expressed on antibodies with specificity for Trypanosoma cruzi or Schistosoma mansoni antigens, respectively. These immunoaffinity-purified preparations were stimulatory if they were prepared from pools of patients' sera or from the mother's own serum, taken early during her pregnancy. These CBMC did not respond to normal immunoglobulin, and CBMC of neonates born of uninfected mothers did not respond to antibodies against either T. cruzi or S. mansoni, or normal immunoglobulin preparations. We propose that in utero exposure of a fetus to some idiotypes expressed on placentally transferred antibodies induces anti-Id T lymphocyte sensitization, which we detect as a proliferative response by CBMC exposed to immunoaffinity-purified antibodies expressing the relevant idiotypes. This is the first experimental evidence that children born of mothers with chronic infections undergo natural in utero idiotypic manipulations and are born possessing cellular anti-Id reactivity.
Antimicrobial peptides and the enteric mucus layer act in concert to protect the intestinal mucosa
Authors: Aline Dupont, Lena Heinbockel, Klaus Brandenburg, Mathias W Hornef
Journal: Gut Microbes (2014)

The intestinal mucosa squares the circle by allowing efficient nutrient absorption while generating a firm barrier toward the enteric microbiota, enteropathogenic microorganisms and high luminal concentrations of potent immunostimulatory molecules. The mucus layer together with local antimicrobial and anti-inflammatory peptides significantly contribute to this ability. Here we summarize the recent progress made to better understand the critical importance of this dynamic, complex and highly structured anti-inflammatory and antimicrobial barrier.
Laboratory Testing to Save Expenses
Authors: Harold E. Resinger
Journal: JAMA (1983)

<h3>To the Editor.—</h3> It is being widely stated that the new Tax Equity and Fiscal Responsibility Act/Diagnosis Related Groups laws and regulations will change the practice of clinical pathology greatly and may decimate it. The idea that it will change is valid, but the idea that will be decimated is not. Out of these governmental adversities have come outstanding opportunities. Under the new laws and regulations, hospital administration will direct its primary efforts toward rapid diagnosis and treatment and early discharge of patients to reduce the cost of hospitalization. The clinical pathologist sits in the best position ever to lead the medical staff and administration in best achieving such. The knowledgeable choice of laboratory tests and efficient management of laboratory operations can maximize the flow-through of patients in achieving appropriate diagnoses and treatment. Either before or immediately on admission, the patient should receive a broad profiling of laboratory tests appropriate
Does gay marriage improve health?
Authors: D. Kamerow
Journal: BMJ (2012)

It’s not only about justice



Two recent events in the United States have brought the issue of same sex marriage back to the top of the news. Firstly, on election day, 6 November, three states legalized same sex marriage and a fourth voted down a ban on same sex marriage. This brought the number of states that have approved gay marriage to nine.

Secondly, the US Supreme Court announced on 7 December that it would take up two cases relating to same sex marriage. They will hear arguments on the cases in the spring of 2013 and rule on them before adjourning in the summer.

The first case will decide whether California voters acted legally when they passed so called Proposition 8 in 2009, which overruled a decision by the California Supreme Court that had permitted gay marriage.

The second case, from New York, challenges a federal law called the Defense of Marriage Act (DOMA), passed in 1996. DOMA, among other things, defined marriage as between only a man and a woman for the purpose of enforcing hundreds of federal laws and …
Population-Based Medicine
Authors: Joel G. Breman
Journal: JAMA (1984)

This book contains 21 reports presented at a conference held in Bellagio, Italy, in November 1980, sponsored by the Rockefeller Foundation and the Institute of Medicine. The editors state that population-based medicine treats the patient as central, but recognizes that the needs of the entire population... create(s) major differences in the needs of health care systems. These needs include the use of valid scientific methods (epidemiology) to rank the importance of problems, the employment of costeffectiveness, the analyses of different interventions, and the promotion of sound managerial techniques to implement the programs.  The essays are divided into five sections: (1)  of Populations, (2) Epidemiology and Evaluation of Health Services, (3) Numeracy in Medicine, (4)  Care Institutions: Education, Training and Organization, and (5) Population-Based Medicine: Perspectives and Problems.  A problem inherent in a potpourri of this sort is that no one subject is covered in sufficient depth for the
Soviet Socialized Medicine: An Introduction
Authors: David W. Wallwork
Journal: JAMA (1967)

Designed primarily for laymen, this introduction to the Soviet health services serves as the to a comprehensive work intended for scholars in the field of medical organization and administration. The author is a sociologist who has impressive knowledge of the historical background of Soviet sociology, especially as it pertains to the Soviet health service. His dispassionate objectivity provides a refreshing contrast to the obvious overtones of some who discussed the system in relationship to recent socioeconomic changes in American medicine. For the American physician concerned with the future of American medicine, it provides a brief history, description, and review of a system entirely different from his own. The system is not judged as good or bad but only as reasonably effective in fulfilling the mission assigned to medicine in Soviet ideology and planning. The author broadly outlines the rationale of its possibly greater appeal than the American system to underdeveloped