tbuckley/cabot-search huggingface dataset:
ET-24 * A NOVEL TROJAN HORSE FOR IN-VIVO SENSITIVITY TESTING OF MEDULLOBLASTOMA THERAPIES
Authors: O. Jonas, S. Sengupta, D. Calligaris, M. Poe, K. Methuku, J. P. Francois, J. Cook, N. Agar, S. Pomeroy, R. Langer
Journal: Neuro-Oncology (2014)

INTRODUCTION: Neural tumors such as medulloblastomas, have distinct genetic signatures, including neurotransmitter receptors, indicative of their developmental lineage. Neurotransmitter receptors have been well-defined in normal neurophysiological, developmental, and pharmacological settings. However, their importance in the maintenance and progression of brain tumors and, importantly, the effect of their targeting in brain cancers remains unclear. In a recent genomic study of primary medulloblastomas, high levels of GABRA5 expression were observed in a particularly aggressive molecular subtype of medulloblastoma (MYC-amplified). We then went on to demonstrate that modulation of GABRA5 receptor activity in these tumors could alter their survival characteristics and provide a novel treatment strategy for individuals diagnosed with this subtype of medulloblastoma. Using a novel implantable device for high-throughput in-vivo drug sensitivity measurements we performed the first in-vivo efficacy studies of several lead compounds. These lead compounds will be further developed to reduce their potential toxicity and side-effects. METHODS: We used an implantable device to treat flank medulloblastoma tumors expressing GABRA5 in vivo with local microdoses of cisplatin and GABA receptor agonists, such as diazepam, QHii066, and other similar derivatives. We compared these to non-GABRA5 expressing tumors. Our results revealed significantly higher apoptosis induction by these compounds in GABRA5 expressing flank tumors with the GABA receptor agonists, whereas we do not see a similar effect with Cisplatin. The converse is true for the non-GABRA5 expressing tumors. CONCLUSION: This is the first successful in-vivo study demonstrating that tumors expressing GABRA5 are sensitive to GABRA5 agonists, providing a more efficient and potentially less toxic approach to developing GABRA5 agonists and other compounds. Validation of targets and identification of the most active lead compounds in vivo before pharmacological optimization may represenent a new paradigm for developing drugs more efficiently in whole animal or human studies in the future.
Liver cell dysplasia: What is its significance?
Authors: Peter B. Anthony
Journal: Hepatology (1987)

Liver cell dysplasia (LCD) was investigated for hepatitis B virus (HBV) markers, alpha-fetoprotein (AFP) and ferritin by serologic and immuno-histochemical methods in 101 patients with cirrhosis. LCD was found in 30 cases (29.7%), with the highest incidence in cases of posthepatitic cirrhosis (67%). In the group of dysplastic cirrhosis (DC) 46.6% of the patients had active HBV infection (hepatitis B surface antigen [HBsAg] serum positivity) compared with 7% of the patients with nondysplastic cirrhosis (NDC) ( P &lt; 0.01). The mean serum AFP concentration was significantly raised in the DC group compared with that in the NDC group ( P &lt; 0.05). In seven patients with LCD at the initial biopsy, the histologic follow-up showed the persistence of LCD in all cases, and the development of hepatocellular carcinoma (HCC) in three cases. In serologic HBsAg-positive cases, dysplastic cells, at variance with the surrounding liver parenchyma, were almost always negative for tissue HBsAg, and always negative for tissue hepatitis B core antigens (HBcAg). AFP was never detected in either normal or dysplastic cells. Ferritin was found in all cases, but dysplastic foci displayed a lesser amount of this protein. These serologic and immunohistochemical data strongly suggest a preneoplastic significance of LCD. The importance of monitoring cirrhotic patients with LCD and particularly those with HBV infection and/or increased AFP levels with more aggressive follow-up is also stressed. An assessment was made of the frequency of liver cell dysplasia and the mean age of each group in 56 normal, 13 cirrhotic, and 50 hepatocellular carcinoma (HCC) patients, 40 with cirrhosis, from southern Africa. Dysplasia increased from 7.1% in normal subjects to 38.5% in cirrhotic, 40% in non-cirrhotic HCC, and 52.5% in cirrhotic HCC patients, three statistically similar frequencies. Average patient ages were as follows: patients with normal livers, 37.3 years; with cirrhosis, 42.4 years; with noncirrhotic HCC, 36.5 years; and with cirrhotic HCC, 34 years, the mean age with dysplasia being lower than that of the whole group. With no increase in frequency of dysplasia from cirrhosis to HCC with cirrhosis, with a similar high frequency in HCC without cirrhosis, and with a mean age of all HCC patients 8 years less than that of cirrhotics and 3 years less than normals, chronologic evolutionary progression from cirrhosis to dysplasia to HCC in southern Africa cannot be demonstrated.
TLR‐related pathway analysis: novel gene–gene interactions in the development of asthma and atopy
Authors: N. E. Reijmerink, R. W. B. Bottema, M. Kerkhof, J. Gerritsen, F. F. Stelma, C. Thijs, C. P. Van Schayck, H. A. Smit, B. Brunekreef, G. H. Koppelman, D. S. Postma
Journal: Allergy (2009)

The toll-like receptor (TLR)-related pathway is important in host defence and may be crucial in the development of asthma and atopy. Numerous studies have shown associations of TLR-related pathway genes with asthma and atopy phenotypes. So far it has not been investigated whether gene-gene interactions in this pathway contribute to atopy and asthma development.One hundred and sixty-nine haplotype tagging single nucleotide polymorphisms (SNPs) of 29 genes (i.e. membrane and intracellular receptors, TLR4 or lipopolysaccharide-binding/facilitating proteins, adaptors, interleukin-1 receptor associated kinases, kinases, chaperone molecules, transcription factors and inhibitors) were analysed for single- and multilocus associations with atopy [total and specific immunglobulin E (IgE) at 1-2 and 6-8 years] and asthma (6-8 years). A total of 3062 Dutch children from the birth cohorts PIAMA, PREVASC and KOALA (Allergenic study) were investigated. Chi-squared test, logistic regression and the data mining approach multifactor dimensionality reduction method (MDR) were used in analysis.Several genes in the TLR-related pathway were associated with atopy and/or asthma [e.g. IL1RL1, BPI, NOD1, NOD2 and MAP3K7IP1]. Multiple, single associations were found with the phenotypes under study. MDR analysis showed novel, significant gene-gene interactions in association with atopy and asthma phenotypes (e.g. IL1RL1 and TLR4 with sIgE to indoor allergens and IRAK1, NOD1 and MAP3K7IP1 with asthma). Interestingly, gene-gene interactions were identified with SNPs that did not have an effect on their own.Our unbiased approach provided suggestive evidence for interaction between several TLR-related pathway genes important in atopy and/or asthma development and pointed to novel genes.
ARE ATRIAL ARRHYTHMIAS UNDER-RECOGNIZED IN PATIENTS WITH CARDIAC SARCOIDOSIS?
Authors: Matthew Cain, Mark Metzl, Amit Patel, Nadera J. Sweiss, Karen Patterson, Kyle Hogarth, James Hansen, Sorin Lazar, Kevin Tsai, John Shin, Joshua Moss, Martin Burke, Hemal Nayak, John Beshai
Journal: Journal of the American College of Cardiology (2012)
Evidence-Based Practice in Primary Care
Authors: Thomas McGinn
Journal: Annals of Internal Medicine (1999)

Medical Writings: Book Notes7 September 1999Evidence-Based Practice in Primary CareThomas McGinn, MD, MPHThomas McGinn, MD, MPHMount Sinai School of Medicine, New York, New York. (McGinn)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-131-5-199909070-00024 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Ridsdale L; ed. 209 pages. London: Churchill Livingstone; 1998. $29.95. ISBN 044305889X. Order phone 800-543-1918.Field of medicine: General internal medicine, family practice, and pediatrics.Format: Softcover book.Audience: Primary care providers in internal medicine, family practice, and pediatrics and primary care residents. Some information pertains only to general practitioners in England.Purpose: To bring together emerging strategies for continuing learning with primary care.Content: Ten chapters cover the major areas of evidence-based medicine (EBM). The first chapters deal with developing a question and searching the literature. The remaining chapters discuss such topics as understanding diagnostic tests, treatment trials, clinical ... Author, Article, and Disclosure InformationAffiliations: Mount Sinai School of Medicine, New York, New York. (McGinn) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 7 September 1999Volume 131, Issue 5Page: 400KeywordsClinical trialsEvidence based medicineLower back painPediatricsPrimary care physiciansResearch reporting guidelinesSoftware toolsTreatment guidelines ePublished: 15 August 2000 Issue Published: 7 September 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Evaluation of a possible role for antimutagens, antiteratogens, and anticarcinogens in reducing environmental health hazards.
Authors: N Nashed
Journal: Environmental Health Perspectives (1976)

The use of protective agents (e.g., sulfhydryl compounds, certain vitamins, amino acids, cations, and antibiotics) offers a novel and promising means of dealing with the ever increasing burden of environmental hazards facing man. Through the daily uptake of minimal doses as a prophylactic measure by the most endangered groups of the population or by direct mixing of the appropriate protective agent with the inducer (e.g., pesticides or anticancer drugs) it should be possible to reduce or prevent some of the most serious toxic side effects including those of a mutagenic, teratogenic or carcinogenic nature. Among some of the most outstanding protection examples cited are the antimutagenic, antiteratogenic and anticarcinogenic effects of L-cystein, and of some of the vitamins. However, in view of our limited understanding of protection mechanisms in this fairly new field of research and due to the toxic side effects of some of the protection agents themselves, a large-scale application of this approach cannot be recommended as yet. More research is urgently needed to study protection mechanisms in suitable standardized model systems and to develop safer and more efficient protective agents.
Phenytoin Toxicity and Co-trimoxazole
Authors: M. A. GILLMAN
Journal: Annals of Internal Medicine (1985)

Letters and Corrections1 April 1985Phenytoin Toxicity and Co-trimoxazoleM. A. GILLMAN, M.D., R. SANDYK, M.D.M. A. GILLMAN, M.D.Search for more papers by this author, R. SANDYK, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-102-4-559_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Phenytoin has been shown to interact with a number of drugs to cause toxicity (1). We report an interaction between phenytoin and co-trimoxazole in a 4-year-old girl with epilepsy who was treated with phenytoin, 200 mg/d, 60 units once per week intramuscularly, and sulthiame, 100 mg/d, which controlled the epilepsy.A 4-year-old girl developed an upper respiratory tract infection that was treated with co-trimoxazole, 10 mg twice daily (5 mg is equivalent to trimethroprim, 40 mg, and sulfamethoxazole, 200 mg). Within 48 hours she developed slurred speech, limb ataxia, bilateral horizontal nystagmus, and marked drowsiness. A routine...References1. PERUCCARICHENS EA. Anti-convulsant drug interactions. In: TYRER JH, ed. The Treatment of Epilepsy. Lancaster, England: NTP Press; 1980:95-128. Google Scholar2. HOUGHTONRICHENS GA. Phenytoin intoxication induced by sulthiame in epileptic patients. J Neurol Neurosurg Psychiatry. 1974;37:275-81. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: South African Brain Research Institute Orange Grove 2192 South Africa PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByInteractions Between Antiepileptic and Antibiotic Drugs: A Systematic Review and Meta-Analysis with Dosing ImplicationsPhenytoin and fosphenytoinAntiepileptic drugsTrimethoprim/sulfamethoxazole-induced phenytoin toxicity in the elderly: a population-based studyTrimethoprim-sulphamethoxazole does not affect the pharmacokinetics of sirolimus in renal transplant recipientsTopical Review: Acute Neurologic Complications in Children With Systemic CancerDrug Interactions with Antimicrobial AgentsIatrogenic Illness in Hospitalized Elderly PeopleToxicities of Antimicrobial Agents Used to Treat OsteomyelitisMiscellaneous antibacterial and antiviral drugs 1 April 1985Volume 102, Issue 4Page: 559-559KeywordsAdverse reactionsAtaxiaEpilepsyNystagmusToxicityUpper respiratory tract infections Issue Published: 1 April 1985 PDF DownloadLoading ...
Regional Cerebral Blood Flow Measurement Using a Scintillation Camera
Authors: WOLF-DIETER HEISS
Journal: Clinical Nuclear Medicine (1979)

A scintillation camera connected to auxillary equipment with off-line data processing or connected to an on-line dedicated computer system permits measurement of hemispheric and regional cerebral blood flow. Reliable flow values are obtained from regions limited in size by spatial resolution and the count rates achieved. Flow measurements obtained with the camera are able to resolve inhomogeneities of cerebral circulation in normal subjects. In a variety of clinical conditions, the localization, severity and extent of flow alterations are shown. Results of flow measurements in individual cases elucidate the pathogenesis of neurologic deficits, quantify the damage to the brain, indicate therapeutic measures of potential value and permit an estimation of the further clinical course. With restricted spatial resolution, flow measurements after intravenous 133Xe injection are also feasible.
PREANESTHETIC MEDICATION WITHOUT NARCOTICS
Authors: T. Stacy Lloyd
Journal: JAMA (1960)

To the Editor:—  InThe Journal, June 18, page 797, appeared the paper Preanesthetic Medication Without Narcotics by Dr. George Wallace of Brooklyn. Physicians who give the paper only a cursory glance may conclude that one should employ a drug such as racephedrine hydrochloride or amphetamine phosphate as a preanesthetic agent in accord with Dr. Wallace's recommendations that one use a sympathomimetic agent. He recommends such drugs as atropine and scopolamine, which are not sympathomimetic but parasympatholitic. Some of the effects of the parasympatholitic drugs are similar to those of the sympathomimetic drugs, but for pharmacological purposes the proper words should be used in the proper places.
Lung bioavailability of generic and innovator salbutamol MDIs.
Authors: H Chrystyn, S A Corlett, V Silkstone
Journal: Thorax (1996)

Pressure on working hours has led to a decrease in opportunities for training in invasive medical procedures for junior doctors. The effect of a structured course on immediate and medium-term changes in self-reported confidence was investigated. A one-day model-based practical course was run on two separate occasions teaching central venous line placement, lumbar puncture, Seldinger-technique chest drain insertion and knee joint aspiration. Attendees were asked to indicate their confidence in each procedure on a 10-point Likert scale before, immediately after and three months after the course. Significant improvements in self-reported confidence were seen for all procedures which were sustained at three months. Feedback was universally positive. Practical pre-clinical training may be a useful adjunct to patient-based training in invasive procedures. The course was particularly popular with foundation year trainees: ideally this training should be available before trainees9 first exposure in the clinical setting.
Surveying the Dying: Medical Epidemiology and the Terminally Ill
Authors: Eric Amster
Journal: Annals of Internal Medicine (2006)

On Being a Doctor19 September 2006Surveying the Dying: Medical Epidemiology and the Terminally IllEric Amster, BAEric Amster, BAFrom the University of California Davis, Davis, California.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-145-6-200609190-00014 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail We can give them no other information except that we do not know: We do not know where it comes from, we do not know how you get it or why it kills you, but we know that it will. Epidemiologists have determined that here in Mexico most persons with idiopathic pulmonary fibrosis will die within 2 to 3 years of their diagnosis. As physicians, we are left to do the only thing we can, which is to ask: “How many months of your life have you lived within the municipal limits of Mexico City? Have you ever seen cockroaches, ... Author, Article, and Disclosure InformationAffiliations: From the University of California Davis, Davis, California.Corresponding Author: Eric Amster, BA, UC Davis Office of Medical Education, One Shields Avenue, Davis, CA 92122. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 September 2006Volume 145, Issue 6Page: 471KeywordsEpidemiologyFearInterstitial lung diseasesMedical educationMemoryPatientsPulmonary diseasesQuestionnairesSarcoidosisScleroderma ePublished: 19 September 2006 Issue Published: 19 September 2006 Copyright & PermissionsCopyright © 2006 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Clinical Guide to Laboratory Tests
Authors: David Chou
Journal: JAMA (1984)

The<i>Clinical Guide to Laboratory Tests</i>potentially provides valuable information in a condensed format, especially for the house officer or nurse needing a quick reference. Despite these advantages, it is a difficult book to review, particularly because its very strengths in presenting large amounts of information result in weaknesses. For example, explanations on serum glucose measurements and the glucose tolerance test are as complete as expected, including references from the National Diabetes Data Group. Conversely, descriptions of the sweat chloride test include only a mention of reference values established at the University of Kentucky Medical Center, Lexington, and a questionable comment on possible false-negative results caused by "excessive sweating during hot weather." In addition, there is no reference to the Cystic Fibrosis Report (<i>J Pediatr</i>1976; 88(II):711-750) or a similar report that might provide an authoritative source of information. Unfortunately many other test discussions also cite only textbooks or locally
Hospital Admission Surveillance Programs
Authors: Edward A. Wolpert
Journal: JAMA (1972)

<h3>To the Editor.—</h3> I was interested in the account Dr. Flashner and associates gave of the HASP Program in Illinois in the Sept 4 issue of<i>JAMA</i>. I would like to point out that what Dr. Flashner says does not tell the entire story of monitoring programs in Illinois. Illinois has<i>two</i>distinctly different models for monitoring care of indigent patients. One is that described by Dr. Flashner and applies to patients in each specialty except psychiatry. The second model applies to psychiatry only. In that model, the State Department of Mental Health serves the monitoring function for the care of indigent patients in private hospitals operating under contract with the state, while the State Department of Public Aid pays for the treatment. The two different approaches represent considerably different philosophies and I do not think that physicians knowledgeable of the two different approaches would necessarily choose HASP monitoring over
ABC of Atrial Fibrillation: ANTITHROMBOTIC TREATMENT FOR ATRIAL FIBRILLATION
Authors: G. Y H Lip, G. D O Lowe
Journal: BMJ (1996)

Summary Antithrombotic prophylaxis with long term warfarin or aspirin reduces thromboembolic risk in atrial fibrillationIdentification, risk assessment, and regular review of all patients with atrial fibrillation should be routine in general and hospital practiceRisk stratification is easily performed on clinical grounds—echocardiography may refine it
Mechanisms of virus-induced asthma exacerbations: state-of-the-art. A GA<sup>2</sup>LEN and InterAirways document
Authors: N. G. Papadopoulos, P. Xepapadaki, P. Mallia, G. Brusselle, J.‐B. Watelet, M. Xatzipsalti, G. Foteinos, C. M. Van Drunen, W. J. Fokkens, C. D'Ambrosio, S. Bonini, A. Bossios, Jan Lötval, P. Van Cauwenberge, S. T. Holgate, G. W. Canonica, A. Szczeklik, G. Rohde, J. Kimpen, A. Pitkäranta, M. Mäkelä, P. Chanez, J. Ring, S. L. Johnston
Journal: Allergy (2007)

Viral infections of the respiratory tract are the most common precipitants of acute asthma exacerbations. Exacerbations are only poorly responsive to current asthma therapies and new approaches to therapy are needed. Viruses, most frequently human rhinoviruses (RV), infect the airway epithelium, generate local and systemic immune responses, as well as neural responses, inducing inflammation and airway hyperresponsiveness. Using in vitro and in vivo experimental models the role of various proinflammatory or anti-inflammatory mediators, antiviral responses and molecular pathways that lead from infection to symptoms has been partly unravelled. In particular, mechanisms of susceptibility to viral infection have been identified and the bronchial epithelium appeared to be a key player. Nevertheless, additional understanding of the integration between the diverse elements of the antiviral response, especially in the context of allergic airway inflammation, as well as the interactions between viral infections and other stimuli that affect airway inflammation and responsiveness may lead to novel strategies in treating and/or preventing asthma exacerbations. This review presents the current knowledge and highlights areas in need of further research.