tbuckley/cabot-search huggingface dataset:
Management of Inadvertent Carotid Artery Sheath Insertion During Central Venous Catheter Placement
Authors: Carlos F. Bechara, Neal R. Barshes, George Pisimisis, Panos Kougias, Peter H. Lin
Journal: JAMA Surgery (2013)

Inadvertent carotid sheath insertion during central venous catheter placement could lead to serious complications.To describe management of inadvertent carotid artery sheath insertion placed intraoperatively during attempted jugular venous cannulation for pulmonary artery catheter placement.In a retrospective medical record review of patients from hospitals affiliated with Baylor College of Medicine, Houston, Texas, a total of 12 patients over 11 years who sustained intraoperative carotid artery introducer sheath placement during attempted jugular vein cannulation were identified. Six patients underwent immediate carotid artery exploration with sheath removal and primary repair. The remaining 6 patients underwent percutaneous closure using a suture-mediated closure device. Treatment outcomes of these 2 groups were analyzed.Technical success, duration of treatment, stroke, return to the operating room, and long-term outcomes.Technical success was achieved in all patients in both groups. The intended operations were aborted in all patients following catheter removal and carotid artery closure. The mean (SD) durations of treatment for the operative and endovascular groups were 32 (12) minutes and 6 (3) minutes, respectively (P = .03). No neurological deficit occurred in either group. The intended operations were all subsequently performed, and the mean delays of operation in the operative and endovascular groups were 5 and 3 days, respectively (P = .20). Follow-up carotid duplex showed no injury of the repaired artery in either group. During a mean follow-up of 42 months, no complications or neurological deficits were noted in either patient cohort.Inadvertent carotid artery sheath placement during attempted central venous cannulation for pulmonary artery catheter insertion mandates catheter removal and repair of the carotid artery puncture site. The closure device permits percutaneous repair of the carotid artery expeditiously. Our experience showed this treatment modality to be as safe and effective as operative repair.
Abstract 4398: Maytansinoid release from thioether linked antibody maytansine conjugates (AMCs) under oxidative conditions: Implication for formulation and for <i>ex vivo</i> sample analysis in pharmacokinetic studies
Authors: Nathan Fishkin, Erin Maloney, Ravi Chari, Rajeeva Singh
Journal: Cancer Research (2010)

Abstract Several antibody—maytansinoid conjugates (AMCs) are in various stages of clinical testing, with the most advanced being trastuzumab-DM1 (T-DM1) in Phase III testing. In T-DM1, the maytansinoid, DM1, is linked to the trastuzumab antibody via a non-reducible (“non-cleavable”) thioether bond using the SMCC (N-succinimidyl-4-(N-maleimidomethyl)-cyclohexane-1-carboxylate) linker. It has been reported that T-DM1 shows evidence of maytansinoid loss in circulation over time based on ex vivo analysis (Liepold, AACR 2009 abstract #2914), and it has been assumed that a slow retro-Michael reaction is the cause of some linker cleavage. In the present study, however, we demonstrate that a more likely source of observed maytansinoid release is a reaction generated ex vivo. In our study, we used a model synthetic compound, DM1-MCC, which has the DM1 maytansinoid linked via a thioether bond like that in T-DM1, and also a thioether-linked AMC. When incubated in human plasma ex vivo, these were found to release maytansinoid sulfonate (DM1-SO3-) under physiological conditions (37°C, pH 7.4) at a slow rate. The formation of an initial sulphenic acid intermediate (RSOH) during β-elimination was confirmed with trapping experiments using dimedone (5,5-dimethyl-1,3-cyclohexanedione). Oxidatively-stressed AMCs and a model substrate with a more hindered thioether made with the maytansinoid DM4 showed a 3-fold increase in rate of sulfoxide formation, but an 8-fold lower rate of β-elimination compared to unhindered thioethers. DM1-MCC and thioether-linked AMCs were incubated at 37°C with thiol-trapping agents, such as 2,2′-dipyridyldisulfide. No release of DM1-thiol was detected under these conditions. In contrast, greater than 20% of conjugated maytansinoid was cleaved from a thioether-linked AMC under oxidative stress conditions (10−6 M H2O2 1 hr, 4°C dialysis, then incubation 18 h at pH 7.4, 37 °C). The present observations suggest that ex vivo thioether oxidation may lead to maytansinoid release from conjugates. This sulfoxide elimination is noted at 37 °C under aqueous conditions and is likely facilitated by the mildly acidic β-hydrogen on the maleimide (pKa ∼ 25). Oxidation of thioethers (such as methionine) is common during protein extraction and concentration, and the present studies underscore the importance of reducing autooxidation of thioether-linked AMCs with regard to sample handling during pharmacokinetic analyses and conjugate formulation. 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 4398.
How strong is the evidence of a link between environmental chemicals and adverse effects on human reproductive health?
Authors: Richard M Sharpe, D Stewart Irvine
Journal: BMJ (2004)

Surveys show that the public suspects that synthetic (manmade) chemicals released into the environment, especially pesticides, have adverse effects on human health and cause disease, including cancer.In reality, few scientifically documented examples support this view, especially for effects on the general population. 1 However, the observation that many synthetic chemicals have intrinsic hormonal activity-they are "endocrine disruptors"-has reopened this debate. 1Pressure groups have called for all synthetic environmental chemicals with the potential to cause harm to be phased out or banned, whereas the chemical industry argues that such action must be based on proof of harm.Vociferous cases have been made on both sides, each lacking definitive data.Yet it is clear that environmental and lifestyle factors are key determinants of human disease-accounting for perhaps 75% of most cancers. 2 New understanding and emerging results are reshaping our thinking, as is the recognition that establishing cause and effect for environmental chemical exposures is a daunting task.
Psychological Correlates of Hyperprolactinemia in Males
Authors: Maurizio Fava, Giovanni A. Fava, Robert Kellner, Emanuela Serafini, Ismaele Mastrogiacomo
Journal: Psychotherapy and Psychosomatics (1982)

In a previous study with hyperprolactinemic female patients, self-rated hostility, depression and anxiety were significantly higher than in other female patients. The study was repeated in hyperprolactinemic males, using the same psychological assessments. Hyperprolactinemic males were significantly more anxious but did not differ significantly in hostility and depression from other male patients. The findings support the view that the psychological effects of high serum prolactin levels depend in part on interactions with gonadal hormones.
Urea-Cycle Enzymes in Liver Disease
Authors: Henry Brown
Journal: JAMA (1967)

Enzymes catalyzing urea synthesis are of great importance because this is the primary pathway for nitrogen excretion in humans. Of equal importance is the fact that intermediates formed in the urea cycle enter into almost every known metabolic pathway. The urea-cycle enzymes are widely distributed in the plant and animal kingdom, but it is the five known hepatic enzymes with which we are concerned here.<sup>1</sup>The enzymes are carbamyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC), argininosuccinic acid synthetase, argininosuccinase, and arginase. They may be isolated in very pure form from liver homogenates and measured quantitatively. In practice, however, activity measurements in liver homogenates are used as an indication of amount of enzymes present. Through the action of the first urea-cycle enzyme, CPS, the metabolite carbamyl phosphate is formed from the union of ammonia, carbon dioxide, and adenosine triphosphate (ATP) (Figure). Carbamyl phosphate plays a key role at a critical
DETECTION AND IMPACT OF SUBCLINICAL CORONARY AND CAROTID ATHEROSCLEROSIS ON CARDIOVASCULAR RISK PREDICTION AND RECLASSIFICATION IN ASYMPTOMATIC US ADULTS: INSIGHTS FROM THE HIGH RISK PLAQUE BIOIMAGE STUDY
Authors: Usman Baber, Roxana Mehran, Samantha Sartori, Mikkel Schoos, Erling Falk, Henrik Sillesen, Pieter Muntendam, Mario Garcia, John Gregson, Stuart Pocock, Valentin Fuster
Journal: Journal of the American College of Cardiology (2014)
Two and a bit cheers for academic medicine
Authors: John Skelton
Journal: BMJ (2006)

I n 2003 the BMJ, Lancet , and 40 partners founded the International Campaign to Revitalise Academic Medicine (ICRAM; http://bmj.bmjjournals.com/academicmedicine/) because of a general sense that “something is not right with academic medicine.” The suggestion was made that “the diagnosis is not entirely clear…and the treatment is unknown.”1 Oneofthe difficulties, highlighted by Clark and Tugwell, was that “at a time when there is increasing demand for academic medicine to be more accountable…the evidence base for its effectiveness is rather slim.”2 A similar awareness perhaps prompted the development of the movement for Best Evidence Medical Education (BEME; www.bemecollaboration.org/) and the Campbell Collaboration (www.campbellcollaboration.org/ECG/index.asp), an echo of the Cochrane Collaboration that involves several disciplines.

And sure enough, a recent careful systematic review on the efficacy of mentoring “revealed an absence of experimental …
Intravenous Platelet Blockade with Cangrelor during PCI
Authors: Deepak L Bhatt, A Michael Lincoff, C Michael Gibson, Gregg W Stone, Steven McNulty, Gilles Montalescot, Neal S Kleiman, Shaun G Goodman, Harvey D White, Kenneth W Mahaffey, Charles V Pollack, Steven V Manoukian, Petr Widimsky, Derek P Chew, Fernando Cura, Ivan Manukov, Frantisek Tousek, M Zubair Jafar, Jaspal Arneja, Simona Skerjanec, Robert A Harrington
Journal: New England Journal of Medicine (2009)

Intravenous cangrelor, a rapid-acting, reversible adenosine diphosphate (ADP) receptor antagonist, might reduce ischemic events during percutaneous coronary intervention (PCI).In this double-blind, placebo-controlled study, we randomly assigned 5362 patients who had not been treated with clopidogrel to receive either cangrelor or placebo at the time of PCI, followed by 600 mg of clopidogrel. The primary end point was a composite of death, myocardial infarction, or ischemia-driven revascularization at 48 hours. Enrollment was stopped when an interim analysis concluded that the trial would be unlikely to show superiority for the primary end point.The primary end point occurred in 185 of 2654 patients receiving cangrelor (7.0%) and in 210 of 2641 patients receiving placebo (8.0%) (odds ratio in the cangrelor group, 0.87; 95% confidence interval [CI], 0.71 to 1.07; P=0.17) (modified intention-to-treat population adjusted for missing data). In the cangrelor group, as compared with the placebo group, two prespecified secondary end points were significantly reduced at 48 hours: the rate of stent thrombosis, from 0.6% to 0.2% (odds ratio, 0.31; 95% CI, 0.11 to 0.85; P=0.02), and the rate of death from any cause, from 0.7% to 0.2% (odds ratio, 0.33; 95% CI, 0.13 to 0.83; P=0.02). There was no significant difference in the rate of blood transfusion (1.0% in the cangrelor group and 0.6% in the placebo group, P=0.13), though major bleeding on one scale was increased in the cangrelor group, from 3.5% to 5.5% (P<0.001), because of more groin hematomas.The use of periprocedural cangrelor during PCI was not superior to placebo in reducing the primary end point. The prespecified secondary end points of stent thrombosis and death were lower in the cangrelor group, with no significant increase in the rate of transfusion. Further study of intravenous ADP blockade with cangrelor may be warranted. (ClinicalTrials.gov number, NCT00385138.)
Physiological concentrations of insulin induce endothelin-mediated vasoconstriction during inhibition of NOS or PI3-kinase in skeletal muscle arterioles
Authors: E Eringa
Journal: Cardiovascular Research (2002)

Objective: To determine the roles of nitric oxide, endothelin-1 and phosphatidylinositol 3-kinase (PI3-kinase) in acute responses of isolated rat skeletal muscle arterioles to insulin. Methods: Rat cremaster first order arterioles were separated from surrounding tissue, cannulated in a pressure myograph and responses to insulin (4 μU/ml–3.4 mU/ml) were studied without intraluminal blood or flow. Results: Insulin alone did not significantly affect arteriolar diameter. Non-selective antagonism of endothelin receptors, with PD-142893, uncovered insulin-induced vasodilatation (25±8% from baseline at 3.4 mU/ml), which was abolished by inhibition of NO synthesis with NG-nitro-l-arginine (l-NA). Inhibition of NO synthesis alone uncovered insulin-induced vasoconstriction at physiological concentrations (21±5% from baseline diameter at 34 μU/ml), which was abolished by PD-142893. The NO donor, S-nitroso-N-acetyl-penicillamine (SNAP) inhibited insulin-induced vasoconstriction during NOS inhibition, even at a concentration that did not elicit vasodilatation itself. Inhibition of PI3-kinase, an intracellular mediator of insulin-induced NO production, with wortmannin, also uncovered insulin-induced vasoconstriction (13±3% from baseline at 34 μU/ml) that was abolished by PD-142893. Conclusions: Insulin induces both nitric oxide and endothelin-1 activity in rat cremaster first-order arterioles. This study demonstrates for the first time that vasoconstrictive effects of physiological concentrations of insulin during inhibition of NOS activity are mediated by endothelin and that insulin induces endothelin-1-mediated vasoconstriction in isolated skeletal muscle arterioles during inhibition of PI3-kinase. These findings support the hypothesis of altered microvascular reactivity to insulin in conditions of diminished PI3-kinase activity, a prominent feature of insulin resistance.
Polymeric enteral diets as primary treatment of active Crohn's disease: a prospective steroid controlled trial.
Authors: F Gonzalez-Huix, R de Leon, F Fernandez-Banares, M Esteve, E Cabre, D Acero, A Abad-Lacruz, M Figa, M Guilera, R Planas
Journal: Gut (1993)

<h3>ABSTRACT</h3> Some insects use endogenous reverse transcriptase (RT) to make variable viral copy DNA (vcDNA) fragments from viral RNA in linear (lvcDNA) and circular (cvcDNA) forms. The latter form is easy to extract selectively. The vcDNA produces small interfering RNA (siRNA) variants that inhibit viral replication via the RNA interference (RNAi) pathway. The vcDNA is also autonomously inserted into the host genome as endogenous viral elements (EVE) that can also result in RNAi. We hypothesized that similar mechanisms occurred in shrimp. We used the insect methods to extract circular viral copy DNA (cvcDNA) from the giant tiger shrimp (<i>Penaeus monodon</i>) infected with a virus originally named infectious hypodermal and hematopoietic necrosis virus (IHHNV). Simultaneous injection of the extracted cvcDNA plus IHHNV into whiteleg shrimp (<i>Penaeus vannamei</i>) resulted in a significant reduction in IHHNV replication when compared to shrimp injected with IHHNV only. Next generation sequencing (NGS) revealed that the extract contained a mixture of two general IHHNV-cvcDNA types. One showed 98 to 99% sequence identity to GenBank record AF218266 from an extant type of infectious IHHNV. The other type showed 98% sequence identity to GenBank record DQ228358, an EVE formerly called non-infectious IHHNV. The startling discovery that EVE could also give rise to cvcDNA revealed that cvcDNA provided an easy means to identify and characterize EVE in shrimp and perhaps other organisms. These studies open the way for identification, characterization and use of protective cvcDNA as a potential shrimp vaccine and as a tool to identify, characterize and select naturally protective EVE to improve shrimp tolerance to homologous viruses in breeding programs.
A Visit of Exploration
Authors: John Lister
Journal: New England Journal of Medicine (1978)

I HAVE to confess that the title of last month's contribution to this column ("Backward or For-ward?") could not have been more appropriate from a personal point of view because it was written as I made the journey from London to Sydney by the trans-Pacific route. During this westward journey halfway around the world my watch had, of course, been set back 12 hours and then put forward 24 hours when we crossed the international date line, so that I was not sure myself whether I was going backward or forward and hope that this state of personal confusion was . . .
Abstract 4709: NXF2 is a Candidate Biomarker of Mechanical Stress in Breast Cancer
Authors: Jiaxu Wang, Rebecca Barnes, Nathan West, Peter Watson
Journal: Cancer Research (2010)

Abstract Mechanical stress has been implicated as an important factor influencing tumour cell biology. Due to the nature of early stages of breast cancer and its ductal environment and associated stromal changes, origins in ductal changes in gland tension are likely to occur and the associated mechanical forces may contribute to the progression of breast cancer. To identify specific changes in gene expression that might serve as biomarkers of mechanical stress in breast cancer, we applied static tensile forces (0.65 pN/μm2) to breast cancer cell lines via collagen-coated magnetite beads, profiled gene expression changes by Microarray chips, validation by RT-PCR and immunoblotting. Our results showed that mechanical stretch forces altered cell signaling in both MDA-MB-231 and MDA-MB-468 breast cancer cell lines by array chip analysis and 7.24.% genes (4.67% up and 2.57% down regulation) were regulated by mechanical stress in 16822 profiling genes in MDA-MB-231 cell line and 5.79% genes (2.22% up and 3.57% down regulated) was regulated in MDA-MB-468 cell lines. The 0.48% (82/16822) up regulation and the 0.125% (21/16822) down regulation was in complete concordance with Microarray in both cell lines. The validation of the gene expression with significant changes of &amp;gt;1.5-fold in MDA-MB-231 cell line, RT-PCR revealed the up-regulation of LCE2D and NXF2 and down-regulation of PIGH and RAPD1B and confirmed the force-induced genes identified by Microarray. Mechanical stress also increased 2.75 fold NXF2 protein expression level with confirmation of immunoblotting. There were no significant expression changes found relating to hypoxia stress control gene NDRG1, which changed the highest gene in hypoxia control chip. We conclude that mechanical stress promotes early breast cancer progression mediated by multiple signal transduction pathways and that NXF2 is a potential mechanical stress marker in breast cancer progression. 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 4709.
Construct an audiovisual programme.
Authors: E A Brain, C M Bidwell
Journal: BMJ (1979)

Advances in audiovisual technology have provided powerful and varied methods of communication.Events, people, places, and ideas may be presented without delay to a large and widely distributed audience through such media as radio, public or closed circuit television, or even the telephone.Alternatively, by recording a programme on audiotape, slide, videotape, or film such information may be brought to a viewer or listener at a convenient time and place.The range of audiovisual communication available makes it important for you, the author, to consider what each method may accomplish, and select the most suitable medium for your purpose.Is it your primary aim to motivate, excite, change attitudes, inform, or teach ?Is your audience to be widespread and varied, or is it a group with narrowly defined objectives ?Audiovisual experts will be available to help if you are working with a broadcasting company or a television network, but in education they may not be.There are several aspects to consider in making an audiovisual programme; message, medium, script, visual display, audio track, text, and package.
Acetylcysteine in Removal of Bezoar
Authors: Henry A. Schlang
Journal: JAMA (1970)

To the Editor.—  In his chapter on bezoars, Bockus1notes that surgeons performing gastroenterostomy or gastrectomy for pyloric stenosis often find masses of food detritus in the stomach of patients who have been carefully prepared by lavage with a small stomach tube for weeks. We have had occasions to encounter such a mass on an x-ray film series of the upper gastrointestinal (GI) tract in a patient with a chronic obstructing ulcer of the duodenum. Our management with acetylcysteine (Mucomyst) may be of interest to others meeting with such problems. This agent has been used to reduce the viscosity of abnormally viscid pulmonary and bronchial secretions.  Report of a Case.—  A 42-year-old white man was admitted to Tampa (Fla) General Hospital on Dec 22, 1969, with a diagnosis of recurrent carcinoma of the lung. Through Dec 28, there had been little vomiting, but the patient complained of considerable pain
LAPAROTOMY FOR INTESTINAL OBSTRUCTION ON BOARD SHIP
Authors: V. Moxey
Journal: BMJ (1922)

MORANDA.f =JA 1077 years after inoculation, is of no diagnostic value whatever in typhoid fever and is of very doubtful value in paratyphoid fevers unless of markedly high titre.But this in no way detracts from the superlative value of the reaction in the non-inoculated.
Food allergy may predict life threatening asthma in children
Authors: D Shaw
Journal: Thorax (2003)

▴ Roberts G, Patel N, Levi-Schaffer F, et al. Food allergy as a risk factor for life-threatening asthma in childhood: a case-controlled study. J Allergy Clin Immunol2003;112:168–74 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] In this case-control study, food allergy and degree of atopy were assessed as risk factors for life threatening asthma in childhood. Currently, no objective clinical risk factors exist. Nineteen children aged 1–16 years … [1]: {openurl}?query=rft.jtitle%253DJournal%2Bof%2BAllergy%2Band%2BClinical%2BImmunology%26rft.stitle%253DJournal%2Bof%2BAllergy%2Band%2BClinical%2BImmunology%26rft.aulast%253DRoberts%26rft.auinit1%253DG.%26rft.volume%253D112%26rft.issue%253D1%26rft.spage%253D168%26rft.epage%253D174%26rft.atitle%253DFood%2Ballergy%2Bas%2Ba%2Brisk%2Bfactor%2Bfor%2Blife-threatening%2Basthma%2Bin%2Bchildhood%253A%2Ba%2Bcase-controlled%2Bstudy.%26rft_id%253Dinfo%253Adoi%252F10.1067%252Fmai.2003.1569%26rft_id%253Dinfo%253Apmid%252F12847494%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1067/mai.2003.1569&link_type=DOI [3]: /lookup/external-ref?access_num=12847494&link_type=MED&atom=%2Fthoraxjnl%2F58%2F9%2F760.atom [4]: /lookup/external-ref?access_num=000184010600025&link_type=ISI
ADHERENCE TO THE MEDITERRANEAN DIET IS ASSOCIATED WITH RENAL FUNCTION AMONG HEALTHY ADULTS: THE ATTICA STUDY
Authors: Christina A. Chrysohoou, Demosthenes B. Panagiotakos, Christos Pitsavos, John Skoumas, Akis Zeibekis, Christina Kastorini, Constantina Masoura, Efi Tsetsekou, Manolis Kambaxis, Nina Papaioannou, Vasiliki Metaxa
Journal: Journal of the American College of Cardiology (2010)