tbuckley/cabot-search huggingface dataset:
Preclinical Cancer Therapy in a Mouse Model of Neurofibromatosis-1 Optic Glioma
Authors: Balazs Hegedus, Debasish Banerjee, Tu-Hsueh Yeh, Stefan Rothermich, Arie Perry, Joshua B. Rubin, Joel R. Garbow, David H. Gutmann
Journal: Cancer Research (2008)

Abstract Mouse models of human cancers afford unique opportunities to evaluate novel therapies in preclinical trials. For this purpose, we analyzed three genetically engineered mouse (GEM) models of low-grade glioma resulting from either inactivation of the neurofibromatosis-1 (Nf1) tumor suppressor gene or constitutive activation of KRas in glial cells. Based on tumor proliferation, location, and penetrance, we selected one of these Nf1 GEM models for preclinical drug evaluation. After detection of an optic glioma by manganese-enhanced magnetic resonance imaging, we randomized mice to either treatment or control groups. We first validated the Nf1 optic glioma model using conventional single-agent chemotherapy (temozolomide) currently used for children with low-grade glioma and showed that treatment resulted in decreased proliferation and increased apoptosis of tumor cells in vivo as well as reduced tumor volume. Because neurofibromin negatively regulates mammalian target of rapamycin (mTOR) signaling, we showed that pharmacologic mTOR inhibition in vivo led to decreased tumor cell proliferation in a dose-dependent fashion associated with a decrease in tumor volume. Interestingly, no additive effect of combined rapamycin and temozolomide treatment was observed. Lastly, to determine the effect of these therapies on the normal brain, we showed that treatments that affect tumor cell proliferation or apoptosis did not have a significant effect on the proliferation of progenitor cells within brain germinal zones. Collectively, these findings suggest that this Nf1 optic glioma model may be a potential preclinical benchmark for identifying novel therapies that have a high likelihood of success in human clinical trials. [Cancer Res 2008;68(5):1520–8]
Transvenous Cardiac Pacing
Authors: STEPHEN J. GULOTTA
Journal: Circulation (1970)

Optimal electrode position for long-term transvenous cardiac pacing is in the apex of the right ventricle. Intracardiac electrograms, surface electrocardiograms, frontal fluoroscopy, lateral roentgenograms, and pacing threshold levels were studied in two groups of patients: One group was comprised of five patients with permanent pacemakers who had inadvertent malplacement of the pacing catheter, and the second group was composed of six patients undergoing temporary pacing from selected sites within the coronary venous system. The results of this study indicate that the appearance of a characteristic right ventricular endocardial complex recorded from the catheter tip is the most reliable guide to proper electrode placement. Low threshold levels, good position demonstrated roentgenographically, and typical surface electrocardiographic patterns of left bundle-branch block were all noted during intentional and following inadvertent malpositioning of the electrode within the coronary venous system and do not, therefore, guarantee proper positioning. A successful routine for pacemaker insertion has been established which includes fluoroscopy, lateral roentgenograms, intracardiac and surface electrocardiograms, and threshold analysis. Satisfaction of all these tests appears to insure proper electrode positioning.
Growth and Mortality in Children in an African Village
Authors: I. A. McGregor, W. Z. Billewicz, A. M. Thomson
Journal: BMJ (1961)

This communication describes the mortality and growth rates of children in a rural Gambian community.The observations were made in the village of Keneba, where since 1949 the staff of the M.R.C. Laboratories, Gambia, have investigated the health of Africans.Keneba is an African settlement in the West Kiang District of the Protectorate of the Gambia and is typical of the villages situated near the banks of the Gambia river.About 700 inhabitants-Mandinkas-live in dwellings made of mud, grass, or krint (a local bamboo), and maintain themselves almost entirely by agriculture.
The Histone Methyltransferase and Putative Oncoprotein MMSET Is Overexpressed in a Large Variety of Human Tumors
Authors: Heidi Rye Hudlebusch, Eric Santoni-Rugiu, Ronald Simon, Elisabeth Ralfkiær, Henrik Holm Rossing, Jens Vilstrup Johansen, Mette Jørgensen, Guido Sauter, Kristian Helin
Journal: Clinical Cancer Research (2011)

Multiple myeloma SET (Suppressor of variegation, Enhancer of zeste, and Trithorax) domain (MMSET) is a histone lysine methyltransferase deregulated in a subgroup of multiple myelomas with the t(4;14)(p16;q32) translocation and poor prognosis. With the aim of understanding, if MMSET can be involved in other types of cancer we investigated the expression of MMSET protein in different types of human tumors.A monoclonal antibody against MMSET was developed and immunohistochemical staining of tissue microarrays (TMA) containing a large number of tumor samples (n = 3774) and corresponding normal tissues (n = 904) was carried out. Further validations of MMSET expression were carried out on independent, tumor-specific sets of TMAs for urinary bladder (n = 1293) and colon cancer (n = 1206) with corresponding clinicopathological data and long-term follow-up.MMSET protein was highly expressed in different tumor types compared to normal counterparts. Particular frequent and/or high MMSET expression was found in carcinomas of the gastrointestinal tract (stomach, colon, anal canal), small cell lung carcinoma, tumors of the urinary bladder, female genitals, and skin. In bladder cancer, MMSET expression correlated with tumor aggressiveness. In contrast, MMSET expression was associated with good prognostic factors in colon cancer and was more pronounced in early stages of colon carcinogenesis (dysplasias) than in adenocarcinomas. However, colon cancer patients with high MMSET levels showed a worse 5-year survival.Our data suggest that MMSET has a broader role in cancer than previously anticipated, and further analysis might qualify it as a prognostic marker and a target for the development of therapy against several types of cancer.
Economic Irony and Cost Containment
Authors: CARL B. LYLE
Journal: Annals of Internal Medicine (1979)

Editorials1 February 1979Economic Irony and Cost ContainmentCARL B. LYLE JR., M.D.CARL B. LYLE JR., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-90-2-267 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn this issue (pp. 243-248), Dr. Griner and the medical house staff at Strong Memorial Hospital (1) present data suggesting that the combined efforts of a house staff, faculty, and hospital administration can result in a containment, or even a decrease, in the use of laboratory procedures on a medical teaching service. This is important documentation, and although as yet there are no data to show that habits formed as a house officer will persist throughout a lifetime of practice, at least the groundwork for such future studies has been laid.In recent years, others interested in the economic aspects...References1. GRINER P: Use of laboratory tests in a teaching hospital: long term trends. Reductions in use and relative cost. Ann Intern Med 90:243-248, 1979 LinkGoogle Scholar2. The Final Report of the Committee on the Costs of Medical Care: Medical Care for the American People. Chicago, The University of Chicago Press, 1932 Google Scholar3. America's health and medical costs: a statement from the deans of 110 American medical schools, in Washington Forum 1977. Private Sector Initiative to Control Health Care Cost: Report of the Washington Forum. Hartford, Connecticut, National Fund for Medical Education, 1977, p. 7 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: CARL B. LYLEJR., M.D.Affiliations: Department of Medicine Charlotte Memorial Hospital and Medical Center Charlotte, North Carolina PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1979Volume 90, Issue 2 Page: 267-268 Keywords Forecasting Habits Research laboratories ePublished: 1 December 2008 Issue Published: 1 February 1979 Copyright & Permissions©1979 American College of PhysiciansPDF downloadLoading ...
Measurement of Pulmonary Blood Flow Using the Indicator-Dilution Technic in Patients with a Central Arteriovenous Shunt
Authors: ALFREDO A. RAMIREZ DE ARELLANO, PETER S. HETZEL, EARL H. WOOD
Journal: Circulation Research (1956)

The possibility of measuring pulmonary blood flow in patients with central arteriovenous shunts utilizing the initial portion of indicator-dilution curves was explored in 16 patients by comparing these values for pulmonary blood flow with determinations by the direct Fick method. A good correlation between Fick and indicator-dilution values was obtained, and no systematic differences were demonstrated. The standard deviation of the differences between Fick and dye values was in the order of 20 to 25 per cent.
Retrospective analysis of weekly intravenous immunoglobulin prophylaxis versus intravenous immunoglobulin by IgG level monitoring in hematopoietic stem cell transplant recipients
Authors: Joshua E. Howell, Alison M. Gulbis, Richard E. Champlin, Muzaffar H. Qazilbash
Journal: American Journal of Hematology (2011)

Patients undergoing allogeneic hematopoietic stem cell transplant (allo HCT) have a higher incidence of infections partly due to secondary hypogammaglobulinemia. We evaluated the role of IVIG in allo HCT patients who received prophylactic IVIG 200 mg/kg once weekly regardless of IgG level (Group 1, n = 115) compared with patients who received IVIG based on IgG level <400 mg/dL (Group 2, n = 114). Primary endpoints were the utilization of IVIG, incidence of veno-occlusive disease (VOD), graft-versus-host disease (GVHD), and documented infections within the first 100 days after allo HCT. Patients in both groups were similar except for a higher number of matched unrelated donor (MUD) transplants in Group 2 (62 vs. 41, P = 0.01). There were no significant differences in the incidence all grades of GVHD (55 vs. 50), VOD (2 vs. 0) or infections in the two groups except for a higher incidence of para-influenza infections in group 1 (9 vs. 0, P = 0.003) coinciding with the flu season. We recommend monthly monitoring of IgG level and replacement only if IgG level is <400 mg/dL.
Cardiovascular Risk Factors and Antiretroviral Therapy
Authors: Daniel R. Kuritzkes, Judith Currier
Journal: New England Journal of Medicine (2003)

The advent of potent combination antiretroviral therapy has led to a profound decrease in the rate of illness related to the acquired immunodeficiency syndrome (AIDS) and has significantly improved survival among patients living with human immunodeficiency virus (HIV) infection in the developed world. A concerted effort is now under way to extend these benefits to infected persons living in resource-poor countries. The success of antiretroviral therapy is tempered, however, by the occurrence of drug-related toxic effects in many patients. Improvements in AIDS-free survival mean that many people face the prospect of decades of therapy, and concern about long-term toxic effects . . .
Deacetylase SIRT6 deaccelerates endothelial senescence
Authors: Jianzhong Shen, Wanshu Ma, Yiwei Liu
Journal: Cardiovascular Research (2012)

This editorial refers to ‘SIRT6 protects human endothelial cells from DNA damage, telomere dysfunction, and senescence’ by A. Cardus et al ., pp. 571–579, this issue. 

Vascular endothelial homeostasis is critical to health and is a significant factor in many human diseases. It is established that endothelial cell (EC) dysfunction is one of the earliest pathological steps in the initiation and progression of vascular diseases such as atherosclerosis and vascular remodelling.1–3 How to maintain a healthy or repair an injured endothelial lining of the vasculature has been a scientific mystery and a clinical challenge. In general, two theories have been proposed. On the one hand, it is thought that during their turnover, injured ECs, due to senescence, ageing, or other pathological challenges, might be replaced by circulating EC progenitors that can repopulate the damaged endothelium. Although this hypothesis has undergone rigorous investigation and achieved some promising initial results,4,5 recent studies demonstrated that circulating EC progenitors do not contribute to the regeneration of a damaged endothelium, thus significantly reducing this theory's promise in the field.6 On the other hand, healing damaged EC areas with adjacent mature ECs through their migration and proliferation is still a viable theory.7 In order to achieve this ‘ in situ healing’, however, the pre-existing mature ECs in the vasculature may have to maintain a ‘threshold’ of healthy …
Objective Documentation of Child Abuse and Dissociation in 12 Murderers With Dissociative Identity Disorder
Authors: Dorothy Otnow Lewis, Catherine A. Yeager, Yael Swica, Jonathan H. Pincus, Melvin Lewis
Journal: American Journal of Psychiatry (1997)

OBJECTIVE: The skepticism regarding the existence of dissociative identity disorder as well as the abuse that engenders it persists for lack of objective documentation. This is doubly so for the disorder in murderers because of issues of suspected malingering. This article presents objective verification of both dissociative symptoms and severe abuse during childhood in a series of adult murderers with dissociative identity disorder. METHOD: This study consisted of a review of the clinical records of 11 men and one woman with DSM-IV-defined dissociative identity disorder who had committed murder. Data were gathered from medical, psychiatric, social service, school, military, and prison records and from records of interviews with subjects' family members and others. Handwriting samples were also examined. Data were analyzed qualitatively. RESULTS: Signs and symptoms of dissociative identity disorder in childhood and adulthood were corroborated independently and from several sources in all 12 cases; objective evidence of severe abuse was obtained in 11 cases. The subjects had amnesia for most of the abuse and underreported it. Marked changes in writing style and/or signatures were documented in 10 cases. CONCLUSIONS: This study establishes, once and for all, the linkage between early severe abuse and dissociative identity disorder. Further, the data demonstrate that the disorder can be distinguished from malingering and from other disorders. The study shows that it is possible, with great effort, to obtain objective evidence of both the symptoms of dissociative identity disorder and the abuse that engenders it. (Am J Psychiatry 1997; 154:1703–1710)
Association Between Preoperative 25-Hydroxyvitamin D Level and Hospital-Acquired Infections Following Roux-en-Y Gastric Bypass Surgery
Authors: Sadeq A. Quraishi, Edward A. Bittner, Livnat Blum, Mathew M. Hutter, Carlos A. Camargo
Journal: JAMA Surgery (2013)

Postoperative hospital-acquired infections (HAIs) may result from disruption of natural barrier sites. Recent studies have linked vitamin D status and barrier site integrity.To investigate the association between preoperative vitamin D status and the risk for HAIs.A retrospective analysis was performed using propensity score methods to construct a matched-pairs cohort to reduce baseline differences between patients with 25-hydroxyvitamin D (25[OH]D) levels less than 30 ng/mL vs 30 ng/mL or greater. Multivariable logistic regression analysis was then performed to examine the association between 25(OH)D levels and HAIs while adjusting for additional perioperative factors. Locally weighted scatterplot smoothing was used to depict the relationship between increasing 25(OH)D levels and the risk for HAIs. This study was conducted in a single, teaching hospital in Boston, Massachusetts, and involved 770 gastric bypass surgery patients between January 1, 2007, and December 31, 2011.Preoperative 25(OH)D levels.Association between preoperative 25(OH)D levels and the risk for postoperative HAIs.The risk for HAIs was 3-fold greater (adjusted odds ratio, 3.05; 95% CI, 1.34-6.94) in patients with 25(OH)D levels less than 30 ng/mL vs 30 ng/mL or greater. Further adjustment for additional perioperative factors did not materially change this association. Locally weighted scatterplot smoothing analysis depicted a near inverse linear relationship between vitamin D status and the risk for HAIs for 25(OH)D levels around 30 ng/mL.In our patient cohort, a significant inverse association was observed between preoperative 25(OH)D levels and the risk for HAIs. These results suggest that preoperative 25(OH)D levels may be a modifiable risk factor for postoperative nosocomial infections. Prospective studies must determine whether there is a potential benefit to preoperative optimization of vitamin D status.
Anaphylactoid Reaction to Demethylchlortetracycline (Ledermycin)
Authors: R. B. Coles, J. Phillips, J. B. Nuttall
Journal: BMJ (1967)

further detail we can say that the retro- spective and prospective techniques are equally important and highly interdependent, and until this fact is acknowledged we will continue to report relatively slow progress in the identification of the different causes of coronary heart disease and other chronic conditions.In our view the ideal approach to the study of chronic disease would combine the prospective and retrospective techniques in one community study.In this way clinicians and pathologists would share the same insights into techniques with workers in the preventive fields, and consistent stan-dards and a shared methodology would con- tribute to the validity and significance of results.-Weare, etc.,
EPstein-barr virus in inflammatory diseases of the liver and liver allografts: Anin situ hybridization study
Authors: Stefan G. Hubscher, Ann Williams, Suzanne M. Davison, Lawrence S. Young, Gerald Niedobitek
Journal: Hepatology (1994)

The Epstein–Barr virus is associated with a broad spectrum of lymphoproliferative diseases in liver allograft recipients. To investigate the effects of primary infection in children following liver transplantation and the possible role of Epstein–Barr virus in the pathogenesis of unexplained chronic hepatitis after transplantation, we used an in situ hybridization technique to detect small virus encoded nuclear RNAs in posttransplant specimens. For comparison, other posttransplant complications and diseases occurring in the nontransplanted liver were studied with the same method. We examined 114 specimens in the following categories: (a) children with primary Epstein–Barr virus infection after transplant (n = 25), (b) chronic hepatitis more than 12 mo after transplant (n = 14), (c) rejection (n = 15), (d) normahear–normal histology more than 12 mo after transplant (n = 13) (e) end–stage acute liver disease (n = 9) and (f) end–stage cirrhosis (n = 38). Thirty–three of 114 specimens had labeling of occasional portal and parenchymal lymphoid cells. These were present in each of the six main diagnostic categories listed above: 2 of 25, pediatric; 6 of 14, chronic hepatitis; 4 of 15, rejection; 1 of 13, normal; 4 of 9, acute; and 16 of 38, cirrhosis. In none of the patients with Epstein–Barr virus–infected cells did lymphoproliferative disease subsequently develop. In conclusion, we have been unable to show an obvious association between Epstein–Barr virus infection and graft dysfunction after liver transplantation. Our results suggest that immunological response to primary infection in children after liver transplantation may be adequate. Small numbers of Epstein–Barr virus–infected cells are present in a wide range of liver diseases. The finding of occasional infected cells in posttransplant biopsy tissue does not predict progression to lymphoproliferative disease. (HEPATOLOGY 1994;20:899-907).
Including Narcotic Addiction Treatment in an Office-Based Practice
Authors: James R. Cooper
Journal: JAMA (1995)

THE REGULATION of narcotic medications used in narcotic addiction treatment is unique in medical therapeutics. Physicians who want to administer or dispense opioid drugs for either narcotic maintenance or detoxification treatment by federal law must first obtain an additional annual registration from the Drug Enforcement Administration (DEA). This registration is separate from the registration familiar to physicians who prescribe other controlled medications. The additional registration is contingent on compliance both with the DEA's security regulations (inventory, record keeping, and physical security) as well as with annual certification from the US Department of Health and Human Services (DHHS). DHHS certification is contingent on approval by individual state drug authorities and compliance with treatment regulations jointly promulgated by the Food and Drug Administration (FDA) and the National Institute on Drug Abuse. Authority for this separate registration emanates from the Narcotic Addict Treatment Act (NATA) of 1974,<sup>1</sup>which was enacted to give
Differences in insulin action as a function of original anatomical site of newly differentiated adipocytes obtained in primary culture.
Authors: C Sztalryd, S Azhar, G M Reaven
Journal: Journal of Clinical Investigation (1991)

Stromal vascular cells were isolated from adipose tissue obtained from three different anatomical locations: epididymal (EPI), retroperitoneal (RP), and dorsal subcutaneous (SC), and allowed to differentiate in primary tissue culture. Cell number, protein concentration, glycerophosphate dehydrogenase, and lipoprotein lipase activity were similar in cells obtained from the EPI, RP, and SC regions, as were total insulin binding and the affinity of insulin for its receptor. However, both maximal insulin receptor tyrosine kinase activity and insulin-stimulated phosphorylation of the insulin receptor were significantly lower (P less than 0.05) in cells cultured from the SC region. In addition, newly differentiated adipocytes from the SC region were less sensitive to the ability of insulin to stimulate glucose uptake, and maximal insulin-stimulated glucose uptake by these cells was also significantly lower (P less than 0.05) when compared to cells obtained from the two other regions. Since these studies were performed on adipocyte precursor cells, allowed to differentiate to a similar degree in primary culture, the observed differences in insulin receptor phosphorylating activity, as well as the ability of insulin to stimulate glucose uptake appear to be intrinsic to adipose tissue from the three sites.