tbuckley/cabot-search huggingface dataset:
124 RANDOMIZED PHASE II CLINICAL TRIAL OF INTRATUMORAL INJECTION OF JX-594, A TARGETED MULTI-MECHANISTIC ONCOLYTIC POXVIRUS, IN PATIENTS WITH HEPATOCELLULAR CARCINOMA
Authors: J. Heo, T. Reid, H.Y. Lim, L. Ruo, C.W. Kim, M. Bloomston, H.C. Chung, B.G. Rhee, R. Patt, C.J. Breitbach, T. Hickman, J.C. Bell, T.H. Hwang, D.H. Kirn
Journal: Journal of Hepatology (2010)
Early Confirmation of Injury in Joggers
Authors: W. A. Boade
Journal: JAMA (1980)

<h3>To the Editor.—</h3> A recent issue ofThe Journalcontains an interesting article by Norfary et al (243:1647, 1980) entitled "Early Confirmation of Stress Fractures in Joggers." We have also noted fractures not only occurring in jogger's extremities, but also abnormalities of the insertion of various muscles, including the case of a 17-year-old boy who maintained a distance of 100 miles per week of strenuous jogging. There had apparently been no change in the boy's jogging method in the recent past or in the associated potential variable, such as jogging shoes or surface on which he jogged. An orthopedist was consulted because pain had developed in the boy's right hip. Findings on x-ray films were completely normal. A radionuclide bone scan (technetium Tc 99m medronate) was performed, showing an abnormality of the insertion of the right adductor brevis muscle (Figure).
Revalidation in the UK
Authors: Zosia Kmietowicz
Journal: BMJ (2005)

STUDY OBJECTIVE--It has been frequently noted that overweight and obesity have a stronger relationship to hypertension and diabetes mellitus than to the risk of stroke. The reason for this observation has not been clear. This study aimed to examine the lifelong relation between body fat and stroke to shed light on why the public health risks of overweight and obesity have tended to be obscured in previous epidemiological studies. DESIGN--Case-control study. SETTING--Eleven general practices in west Birmingham. PARTICIPANTS--Altogether 125 men and women who had just had their first stroke and were aged 35-74 years and 198 controls frequency matched for age and sex were recruited over 24 months during 1988-90. MAIN RESULTS--Those in both the thinnest and fattest quartiles of subscapular skinfold thickness were at increased risk of stroke compared with those in the middle quartiles (age adjusted odds ratios 2.12 (95% confidence interval (CI) 1.2, 3.9) and 2.08 (1.1, 3.8) respectively). When lifelong maximum reported body mass index was assessed the hazards of obesity but not leanness were seen (odds ratio for the highest versus the lowest quartile were--age adjusted, 1.54 (0.8, 3.0) and multiple risk factor adjusted, 2.25 (1.1, 4.5). This lifelong pattern of risk seemed to be established early, the odds ratios for the highest versus the lowest quartile of reported body mass index aged 21 years were--age adjusted, 2.18 (1.1, 4.4) and multiple risk factor adjusted 2.13 (1.1, 4.2). The risks of both maximum reported body mass index and reported body mass index aged 21 years were more clear in those who had never smoked cigarettes (test for trend in odds ratio, p = 0.009 and p = 0.02 respectively). CONCLUSIONS--Potentially important risks of excessive body fat for stroke can be obscured by both a history of cigarette smoking and thinness associated with deteriorating health. The results seem to explain why excess body fat has previously been consistently related to hypertension and diabetes mellitus but less consistently to stroke. Avoiding overweight and obesity during adult life offers protection against stroke.
Glucose Counterregulation in Advanced Type 2 Diabetes: Effect of β-Adrenergic Blockade
Authors: Syed Bokhari, Elena Plummer, Peter Emmerson, Anchal Gupta, Christian Meyer
Journal: Diabetes Care (2014)

To examine counterregulatory glucose kinetics and test the hypothesis that β-adrenergic blockade impairs these in patients with type 2 diabetes mellitus (T2DM) and advanced β-failure.Nine insulin-requiring T2DM subjects and six matched nondiabetic control subjects were studied. β-Cell function was assessed by the C-peptide response to arginine stimulation. Counterregulatory hormonal responses and glucose kinetics were assessed by hyperinsulinemic euglycemic-hypoglycemic clamps with [3-(3)H]glucose infusion. T2DM subjects underwent two clamp experiments in a randomized crossover fashion: once with infusion of the β-adrenergic antagonist propranolol and once with infusion of normal saline.Compared with the control subjects, T2DM subjects had threefold reduced C-peptide responses to arginine stimulation. During the hypoglycemic clamp, glucagon responses were markedly diminished (16.0 ± 4.2 vs. 48.6 ± 6.0 ng/L, P < 0.05), but other hormonal responses and the decrement in the required exogenous glucose infusion rate (GIR) from the euglycemic clamp were normal (-10.4 ± 1.1 vs. -7.8 ± 1.9 µmol · kg(-1) · min(-1) in control subjects); however, endogenous glucose production (EGP) did not increase (-0.8 ± 1.0 vs. 2.2 ± 0.7 µmol · kg(-1) · min(-1) in control subjects, P < 0.05), whereas systemic glucose disposal decreased normally. β-Adrenergic blockade in the T2DM subjects increased GIR ∼20% during the euglycemic clamp (P < 0.01), but neither increased GIR during the hypoglycemic clamp or decreased its decrement from the euglycemic clamp to the hypoglycemic clamp.Overall glucose counterregulation is preserved in advanced T2DM, but the contribution of EGP is diminished. β-Adrenergic blockade may increase insulin sensitivity at normoglycemia but does not impair glucose counterregulation in T2DM patients, even those with advanced β-cell failure.
Fever of Unknown Origin
Authors: William R. Barclay
Journal: JAMA (1977)

One of the most difficult challenges in clinical medicine is arriving at a specific diagnosis for a fever of unknown origin (FUO). The cause of a FUO will frequently remain obscure and frustrate the best diagnostic efforts of an aggressive house staff backed up by learned consultants and a medical center equipped with the latest and most sophisticated diagnostic facilities. The FUOs can be divided into four groups on the basis of their underlying cause: (1) infections, (2) neoplasms, (3) collagen-vasculitis disorders, and (4) miscellaneous (eg, sarcoid). In the most difficult and obscure cases, the clinician may not be able to assign the cause of a FUO to one of these groups and may be reluctant to initiate a trial of corticosteroid therapy for what is believed to be a vasculitis, in case an infection such as tuberculosis is the real villain. Thus, patients with FUO are subjected to a
Eosinophilia During Piperacillin-Tazobactam (Pip/Taz) IV Desensitization
Authors: J.G. Kemp, N.L. Rider, G. Ghaffari, E.L. Pratt, J.G. Gibbs, S. Chegini, T.J. Craig
Journal: Journal of Allergy and Clinical Immunology (2007)
DIPEPTIDYL PEPTIDASE-4 INHIBITOR, SAXAGLIPTIN, ENHANCES NITRIC OXIDE BIOAVAILABILITY IN AORTIC AND RENAL ENDOTHELIUM FROM OBESE, INSULIN-RESISTANT RATS
Authors: Richard Preston Mason, Ruslan Kubant, Adam M. Jacoby, Robert F. Jacob, Aouatef Bellamine, Yoshiko Mizuno, Tadeusz Malinski
Journal: Journal of the American College of Cardiology (2010)
Thrombotic Thrombocytopenic Purpura
Authors: Charles G. Watson
Journal: JAMA (1971)

The etiology of thrombotic thrombocytopenic purpura (TTP) remains obscure. Rickettsial organisms have recently been described in the peripheral blood of one patient with TTP and of two patients with the hemolytic uremic syndrome. The concomitant occurrence of TTP in two siblings has been reported. The concurrence of this disease in husband and wife, reported herein, further suggests an etiology of environmental origin.
TCT-108 Performance and Safety of the TRUE Dilatation™ Balloon Valvuloplasty Catheter for Aortic Balloon Valvuloplasty in Patients Undergoing TAVI
Authors: Felix Woitek, Stephan Haussig, Norman Mangner, Robert Höllriegel, Enno Boudriot, Marion Zimmer, Beate Rott, David Holzhey, Friedrich Mohr, Gerhard Schuler, Axel Linke
Journal: Journal of the American College of Cardiology (2012)
Toxic effects of glucagon-induced acute lipid mobilization in geese
Authors: John C. Hoak, William E. Connor, Emory D. Warner
Journal: Journal of Clinical Investigation (1968)

The toxic effects associated with rapid lipid mobilization and a high plasma free fatty acid (FFA) concentration produced by glucagon were evaluated. Glucagon (0.5 mg/kg of body wt) was injected intravenously into nonfasting geese. The geese developed rapid respirations and high plasma FFA levels within 15 min after the glucagon injection; three of eleven died. Control geese, injected with saline, did not exhibit toxic signs. Peak FFA concentrations developed 15 min after glucagon and high levels persisted for over 90 min. Geese injected with glucagon frequently developed electrocardiographic abnormalities that included supraventricular tachycardia, premature ventricular contractions, and signs of myocardial ischemia. Light and electron microscopy revealed acute myocardial degeneration and fatty infiltration of the liver. The increase in plasma FFA concentrations and toxic effects were not prevented by pretreatment with nicotinic acid or propranolol.
TCT-549 Impact Of Clinical Presentation On In-Hospital Bleeding Outcomes In Percutaneous Coronary Intervention
Authors: Joshua Loh, Hironori Kitabata, Israel Barbash, Danny Dvir, Salem Badr, Rebecca Torguson, Kenneth Kent, Lowell Satler, William Suddath, Augusto Pichard, Ron Waksman
Journal: Journal of the American College of Cardiology (2012)
Unacceptable risk of sudden death without transplantation if low ejection fraction is due to coronary artery disease
Authors: Lynne W. Stevenson, Catherine Chelimsky-Fallick, Jan Tillisch, Jaime Moriguchi, Jon Kobashigawa, Eliyahu Milgalter, Davis Drinkwater, Hillel Laks, Julie Walden
Journal: Journal of the American College of Cardiology (1990)
Transactivator and Structurally Optimized Inducible Lentiviral Vectors
Authors: Karin Haack, Adam S. Cockrell, Hong Ma, David Israeli, Steffan N. Ho, Thomas J. McCown, Tal Kafri
Journal: Molecular Therapy (2004)

Lentiviral vectors offer well-recognized advantages as a gene delivery system both for the analysis of gene function and as a vehicle for gene therapy. In the present study optimized HIV-1-based vector systems that display efficient doxycycline (Dox)-dependent transgene expression in vitro and in vivo have been developed through the modification of factors that contribute to basal activity levels. Dissection of HIV-1 vectors harboring a tTA-dependent transgene expression cassette revealed several mechanisms that account for Dox-independent transgene expression, including those mediated by an internal CMV promoter, as well as a potential contribution from fusion proteins generated by translational readthrough. A precipitous reduction in basal activity levels was accomplished by separating the transactivator and the transgene cassettes into a binary vector system and by relocating the inducible promoter to the U3 region of the LTR. In addition, substituting the VP16 portion of tTA with the human p65 transactivating domain improved Dox-dependent transgene expression in a number of cell types. Optimizing HIV-1-based vectors culminated in a "toolbox" of vectors suitable for transgene delivery in vitro and in vivo, as conveyed by our ability to control the Dox-dependent differentiation of embryonic fibroblasts into muscle cells in vitro and transgene expression in rat brains.
Abstract 4009: Identification of Y726 and Y793 as novel phosphorylation sites in human Flt3 and their role in signaling
Authors: Elena Razumovskaya, Jianmin Sun, Lars Rönnstrand
Journal: Cancer Research (2010)

Abstract Fms-like tyrosine kinase-3 (FLT3), a growth factor receptor expressed in hematopoietic progenitor cells. FLT3 mutations, ITD and D835, are found in approximately 30% of AML patients and correlate with a poor prognosis, thus making receptor a potential therapeutic target. Flt3 mutations cause constitutive activation of the receptor, leading to alteration in signal transduction. The aims of this study are to analyze the kinetics and specificity of FLT3 autophosphorylation in wild-type FLT3 and FLT3 mutants, to identify new phosphorylation sites in FLT3 receptor and to determine related signaling pathways. Using a panel of “homemade” phosphospecific antibodies directed against potential tyrosine phosphorylation sites in FLT3, we identified three novel phosphorylation sites and studied the kinetics and specificity of phosphorylation in living cells. Our results show that activation of the wild-type Flt3 receptor is ligand- dependent and responding in a time dependent manner in contrast to FLT3-ITD and D835Y that are constitutive active and ligand-independent. Eight phosphorylated tyrosine residues (pY589, pY591, pY599, pY726, pY768, pY793, pY842 and pY955) were shown to have different phosphorylation characteristics in the wild-type receptor compared to the mutated receptors. Furthermore, we showed that Y726, Y793 and Y842 are novel phosphorylation sites of FLT3 receptor. Further study on stable transfected cells with Y-to-F mutations (726F and 793F), showed that these sites might be important for cell survival, proliferation and transformation. We could also see decreased phosphorylation of Erk1/2 and SHP2 in mutants compare to wild-type FLT3 or FLT3-ITD. Potential binding partners for Y726 and Y793 were predicted by using synthetic phosphopeptides for probing of SH2 domain arrays. The candidate binding partners will be verified as true binding partners using co-immunoprecipitation experiments. From this study we could observe not only quantitative changes but also qualitative differences in the phosphorylation patterns of wild-type and mutated FLT3 receptors. We have also identified novel phosphorylation sites in FLT3 receptor that can be involved in different signaling pathways. Using this data we can further study the mechanisms of signaling pathways of the Flt3 receptor that are involved in many biological responses and understand the mechanism by which FLT3-ITD and -D835Y functions in pathological conditions. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4009.
Massive Pleural Effusion Secondary to Continuous Ambulatory Peritoneal Dialysis, Confirmed by Tc-99m Sulfur Colloid Peritoneoscintigraphy
Authors: TZU-CHEN YEN, KUN-JU LIN, KAI-YUAN TZEN
Journal: Clinical Nuclear Medicine (2000)

Continuous ambulatory peritoneal dialysis is an effective treatment for end-stage renal disease. Pleural effusion secondary to pleuroperitoneal communication is an unusual complication of continuous ambulatory peritoneal dialysis, with persistence or recurrence requiring an alternate form of dialysis. The authors describe a 62-year-old woman with uremia of unknown cause who suddenly experienced right chest respiratory difficulty after her first continuous ambulatory peritoneal dialysis. Chest radiographs revealed a massive pleural effusion in the right lung. Further Tc-99m sulfur colloid peritoneoscintigraphy confirmed a communication between the peritoneal and pleural cavities on the right side of the diaphragm.
Fundamental Differences in the Circulatory Effects of Various Vasoactive Drugs Used for the Treatment of Shock.
Authors: M. H. Weil
Journal: Annals of Internal Medicine (1964)

s1 October 1964Fundamental Differences in the Circulatory Effects of Various Vasoactive Drugs Used for the Treatment of Shock.M. H. Weil, M.D., Ph.D.M. H. Weil, M.D., Ph.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-61-4-798_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptVasopressor amines are widely used for treatment of acute hypotension and circulatory shock in an effort to restore "normal" or near-normal arterial pressure levels. The circulatory failure clinically regarded as "shock" is primarily a defect of blood flow rather than a deficiency of blood pressure, and vasoconstriction provoked by vasopressor agents may not improve perfusion of vital tissues. The actions of various vasopressor amines in current clinical use were defined in terms of their relative effects on the arterial bed (resistance vessels), the venous bed (capacitance vessels), and the heart. Fundamental differences between vasopressor agents were demonstrated, and the implication... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Los Angeles, Calif. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByIs the Sympathetic System Detrimental in the Setting of Septic Shock, with Antihypertensive Agents as a Counterintuitive Approach? A Clinical Proposition 1 October 1964Volume 61, Issue 4Page: 798-798KeywordsBlood flowBlood pressureDrugsHeartHypotensionShockVasoconstrictionVasopressors Issue Published: 1 October 1964 PDF DownloadLoading ...
Cardiopulmonary Resuscitation-Reply
Authors: Linda Quan
Journal: JAMA (1993)

<h3>In Reply.</h3> —Our study does not contradict the AHA guidelines recommending the Heimlich maneuver for use only for suspected foreign body obstruction in the submersion victim.<sup>1</sup>While bystander CPR was not associated with improved outcome in drowning, the majority of study victims (78%) had received bystander CPR, making comparison difficult between the bystander and no-bystander groups. Moreover, these two groups included victims with both short and long submersion durations. Most submersion victims' fates are determined by the duration of their submersion; we recommended that future studies evaluating an intervention should assess and control for submersion duration. The statement that there are no controlled studies supporting CPR in submersion victims is incorrect. A recent study compared the outcome of submersion victims treated with varying degrees of CPR and controlled for submersion duration.<sup>2</sup>All victims receiving some degree of CPR did better than those who had none; the ones who
Increased Medication Use in Attention-Deficit Hyperactivity Disorder: Regressive or Appropriate?
Authors: Sally E. Shaywitz
Journal: JAMA (1988)

Attention-deficit hyperactivity disorder (ADHD) represents one of the most common and serious neurobehavioral disorders of childhood, affecting children from early childhood into adult life. The cardinal clinical characteristics of the disorder, inattention and, at times, impulsivity and hyperactivity, may interfere with the child's adjustment in every phase of existence, both through time and across experiences. Though its etiology may involve environmental influences,<sup>1</sup>evidence from a number of lines of investigation suggests that biologic factors play an important role in a significant number of cases (S.E.S. and B.A.S., in press). The entity we today label ADHD has undergone multiple transformations over the past century. Some of these are semantic; others, however, are more substantive and reveal significant changes in our understanding of the disorder. Review of the evolution of these changes provides important insights into the current conceptualizations of the disorder. The origins of ADHD can be traced to the
A Pivotal Role for Heat Shock Protein 90 in Ewing Sarcoma Resistance to Anti-Insulin-like Growth Factor 1 Receptor Treatment: <i>In vitro</i> and <i>In vivo</i> Study
Authors: Ana Sofia Martins, José Luis Ordoñez, Alfredo García-Sánchez, David Herrero, Victoria Sevillano, Daniel Osuna, Carlos Mackintosh, Gemma Caballero, Ana Pastora Otero, Christopher Poremba, Juan Madoz-Gúrpide, Enrique de Alava
Journal: Cancer Research (2008)

Abstract Ewing Sarcoma (ES) shows several deregulated autocrine loops mediating cell survival and proliferation. Therefore, their blockade is a promising therapeutic approach. We previously reported the in vitro effect of insulin-like growth factor 1 receptor (IGF1R)/KIT pathway blockade on ES cell lines, and we now extend our observations to changes induced by this treatment in interacting proteins/networks. A proteomic analysis revealed that Heat Shock Protein (HSP)90 was differentially expressed between ES cell lines sensitive and resistant to specific IGF1R/KIT inhibitors. We therefore inhibited HSP90 with 17-allylamino-17-demethoxygeldanamycin (17-AAG) and siRNA, and observed that ES cell line growth and survival were reduced, especially in the resistant cell lines. Conversely, HSP90 induced–expression conferred resistance to anti-IGF1R/KIT treatment in the sensitive cell lines. 17-AAG treatment induced HSP90 client protein degradation, including AKT, KIT, or IGF1R, by inhibiting their physical interaction with HSP90. Xenograft models developed with A673 ES cell line confirmed that HSP90 inhibition, alone or combined with IGF1R inhibition, significantly reduced tumor growth and expression of client proteins. Remarkably, using two independent clinical sample sets, we have found that nearly half of IGF1R-positive tumors also show HSP90 overexpression. This delineates a subset of patients that could benefit from combination of anti-HSP90 agents when considering IGF1R-targeting therapies. Importantly, sensitivity to drugs such as ADW/IMA depends not only on the levels of expression and basal activation of IGF1R/KIT, but also, and for the first time reported in ES, on the development of the stress response mechanism. Accordingly, HSP90 expression could be a predictive factor of response to IGF1R-targeting therapies. [Cancer Res 2008;68(15):6260–70]
BMA reassured over revalidation
Authors: Alex Vass
Journal: BMJ (2001)

The BMA and the General Medical Council, which regulates the medical profession in the United Kingdom, have avoided a split over revalidation procedures after a meeting last week. Dr Ian Bogle, chairman of the BMA's council, said he had been “reassured” over most points.

The BMA had threatened to draw up its own proposals for revalidation after a meeting of the BMA Central Consultants and Specialists Committee …
Prognostic significance of serum anti-p53 antibody in patients with hepatocellular carcinoma
Authors: Goshi Shiota, Yosuke Kishimoto, Akihiko Suyama, Michiko Okubo, Shunsuke Katayama, Ken-ichi Harada, Masato Ishida, Kotaro Hori, Takeaki Suou, Hironaka Kawasaki
Journal: Journal of Hepatology (1997)