tbuckley/cabot-search huggingface dataset:
Mechanism of Sweating From Tricyclics
Authors: John D. Krick
Journal: JAMA (1979)

<h3>To the Editor.—</h3> Drs Klerman and Hirschfeld are to be commended for their excellent overview of antidepressant drugs (240:1403,1978). In the way of clarification, however, I would like to point out that while tricyclic antidepressant drugs exhibit marked anticholinergic effects, this is not the mechanism of the increased sweating seen with the tricyclic antidepressant agents. Indeed, anticholinergic agents decrease, rather than increase, sweating. In addition to their anticholinergic effects, tricyclic antidepressants also display sympathomimetic effects, mediated by their blockade of the "amine pump," and this is undoubtedly the mechanism of the hyperhidrosis.<sup>1,2</sup>
Higher miRNA Tolerance in Immortal Li-Fraumeni Fibroblasts with Abrogated Interferon Signaling Pathway
Authors: Qunfang Li, Michael A. Tainsky
Journal: Cancer Research (2011)

The IFN pathway is abrogated in fibroblasts from Li-Fraumeni syndrome (LFS) patients during spontaneous cellular immortalization, a necessary step in carcinogenesis. Microarray profiling of differentially expressed microRNAs (miRNA) revealed that most miRNAs were upregulated in IFN pathway-defective MDAH087-10 fibroblasts compared with MDAH087-N cells with relatively normal IFN signaling. Overexpression of Dicer, a critical enzyme in miRNA biogenesis, promoted cell growth and colony formation in MDAH087-10 cells. However, double-stranded miRNA produced by Dicer enhanced the expression of IFN-stimulated genes in MDAH087-N cells resulting in significant cell death and reduced cell growth. Furthermore, manipulation of the IFN pathway in immortal LFS fibroblasts through transcription factor IRF7 reversed their response to Dicer overexpression due to changed IFN pathway activity. Dicer overexpressing MDAH087-N cells contained lower levels of miRNA than vector control, and conversely much higher miRNA expression was detected in Dicer-transfected MDAH087-10 cells. Therefore, cells with a defective IFN pathway have a higher miRNA tolerance than cells with normal IFN pathway. This work indicates for the first time that the IFN pathway as mediated through the transcription factor IRF7 must be disrupted to permit miRNA upregulation to occur in early carcinogenesis. The IFN pathway appears to provide a checkpoint for miRNA level tolerance and its abrogation leads to cellular immortalization.
Occupational rhinitis and bronchial asthma due to morphine: evidence from inhalational and nasal challenges
Authors: S. Uliński, C. Pańczyóski, P. Górski
Journal: Allergy (1996)

A case of occupational bronchial asthma due to morphine in a nonatopic 46‐year‐old woman is presented. The following diagnostic tests were used: a workplace trial with bronchodilator and placebo, and single‐blind, placebo‐controlled nasal and bronchial challenge with 0.5% morphine HCl. For the nasal challenge, four asthmatic patients were selected as a control group. The nasal washings were done before and 30 min, 3 h, 24 h, and 48 h after all challenges. In the nasal lavage fluid, the total numbers of eosinophils, neutrophils, basophils, and mast cells were counted, and, after the nasal challenge, total protein and albumin levels were measured. During the workplace trial, the PEF variability ratio increased from 5% to 38%. After the challenges, a decrease in the spirometric parameters (VC and FEV 1 ) of about 30–40% was observed, with minimums at 24 and 48 h. An influx of granulocytes with an increase in the relative number of eosinophils and basophils from 3 h until 48 h after the challenge was observed in the nasal lavage fluid. The protein level in the nasal lavage fluid increased from 190 to 1275 μg/ml 24 h after the challenge with an increase of relative albumin level from 24% to 40% at 24 h. In the control group, no changes in relative number of basophils and eosinophils and albumin/total protein ratio in the nasal lavage fluid or in the spirometric parameters were observed after the challenge.
Left Ventricular Function in Children Studied by Increasing Peripheral Resistance with Angiotensin
Authors: L. JEROME KROVETZ, THOMAS G. MCLOUGHLIN, GEROLD L. SCHIEBLER
Journal: Circulation (1968)

Response to angiotensin infusion was evaluated in 11 normal children and 24 patients with suspected left ventricular dysfunction. This included 12 patients with endocardial fibroelastosis, three with idiopathic myocardial hypertrophy, one with cardiac glycogenosis, and eight with the Hunter-Hurler syndrome. In 20 of these 24 patients, cardiac catheterization findings confirmed the clinical suspicion of decreased left ventricular function. In 11 instances left ventricular dysfunction was diagnosed by an elevation of resting left ventricular end-diastolic pressure. In eight instances this was ascertained by a decrease in resting left ventricular stroke work when compared to the expected range, derived by using a linear regression formula based on 24 normal subjects. In only four instances were both abnormal; that is, the resting left ventricular stroke work was decreased and the left ventricular end-diastolic pressure was increased. In five of these 20 patients, abnormal left ventricular function was elicited only on infusion of angiotensin. Thus this test is a significant adjunct in our ability to determine myocardial malfunction at cardiac catheterization.
Coronary Microvascular Rarefaction and Myocardial Fibrosis in Heart Failure With Preserved Ejection Fraction
Authors: Selma F. Mohammed, Saad Hussain, Sultan A. Mirzoyev, William D. Edwards, Joseph J. Maleszewski, Margaret M. Redfield
Journal: Circulation (2015)

Characterization of myocardial structural changes in heart failure with preserved ejection fraction (HFpEF) has been hindered by the limited availability of human cardiac tissue. Cardiac hypertrophy, coronary artery disease (CAD), coronary microvascular rarefaction, and myocardial fibrosis may contribute to HFpEF pathophysiology.We identified HFpEF patients (n=124) and age-appropriate control subjects (noncardiac death, no heart failure diagnosis; n=104) who underwent autopsy. Heart weight and CAD severity were obtained from the autopsy reports. With the use of whole-field digital microscopy and automated analysis algorithms in full-thickness left ventricular sections, microvascular density (MVD), myocardial fibrosis, and their relationship were quantified. Subjects with HFpEF had heavier hearts (median, 538 g; 169% of age-, sex-, and body size-expected heart weight versus 335 g; 112% in controls), more severe CAD (65% with ≥1 vessel with >50% diameter stenosis in HFpEF versus 13% in controls), more left ventricular fibrosis (median % area fibrosis, 9.6 versus 7.1) and lower MVD (median 961 versus 1316 vessels/mm(2)) than control (P<0.0001 for all). Myocardial fibrosis increased with decreasing MVD in controls (r=-0.28, P=0.004) and HFpEF (r=-0.26, P=0.004). Adjusting for MVD attenuated the group differences in fibrosis. Heart weight, fibrosis, and MVD were similar in HFpEF patients with CAD versus without CAD.In this study, patients with HFpEF had more cardiac hypertrophy, epicardial CAD, coronary microvascular rarefaction, and myocardial fibrosis than controls. Each of these findings may contribute to the left ventricular diastolic dysfunction and cardiac reserve function impairment characteristic of HFpEF.
Use of treadmill score to quantify ischemic response and predict extent of coronary disease.
Authors: K Cohn, B Kamm, N Feteih, R Brand, N Goldschlager
Journal: Circulation (1979)

In this study we assessed whether various responses to exercise testing could be quantified in order to derive the probabilities of presence of coronary disease, and if present, to assess its severity. A treadmill score based on the exercise response was determined in 405 patients who had both treadmill tests and coronary angiograms. The score was derived using discriminant function analysis, by weighting and combining depth and configuration of ST depression (downsloping, horizontal or slowly upsloping), timing onset and duration of ischemia, grading ventricular arrhythmias, heart rate and blood pressure change, coexistence of exercise-induced chest pain and sex. The treadmill score was effective in detecting coronary disease (lesions with an greater than or equal to 50% narrowing), with a predictive accuracy (PA) (probability that a subject manifesting a positive test has disease) of 87%, a true negative rate (TNR) (probability of a subject with a negative test having no disease) of 80%, and sensitivity of 94%. The treadmill score also detected severe disease (triple-vessel, main left and/or greater than 90% proximal occlusion of the left anterior descending artery), with a PA of 73%, TNR of 79% and sensitivity of 82%. We conclude that the exercise response, expressed numerically as a treadmill score, permits analysis of most of the relevant data from exercise testing, increases test accuracy by 10-15% compared with standard criteria for treatmill test interpretation, and enables the derivation of probability statements for presence and severity of coronary disease. The validity of any prediction on the basis of exercise performance may thus be quantitatively judged.
CAAT/Enhancer Binding Protein Homologous Protein–Dependent Death Receptor 5 Induction Is a Major Component of SHetA2-Induced Apoptosis in Lung Cancer Cells
Authors: Yi-Dan Lin, Shuzhen Chen, Ping Yue, Wei Zou, Doris M. Benbrook, Shengquan Liu, Thanh C. Le, K. Darrell Berlin, Fadlo R. Khuri, Shi-Yong Sun
Journal: Cancer Research (2008)

Abstract The flexible heteroarotinoids (Flex-Het) represent a novel type of atypical retinoids lacking activity in binding to and transactivating retinoid receptors. Preclinical studies have shown that Flex-Hets induce apoptosis of cancer cells while sparing normal cells and exhibit anticancer activity in vivo with improved therapeutic ratios over conventional retinoid receptor agonists. Flex-Hets have been shown to induce apoptosis through activation of the intrinsic apoptotic pathway. The present study has revealed a novel mechanism underlying Flex-Het–induced apoptosis involving induction of death receptor 5 (DR5). The representative Flex-Het SHetA2 effectively inhibited the growth of human lung cancer cells in cell culture and in mice. SHetA2 induced apoptosis, which could be abrogated by silencing caspase-8 expression, indicating that ShetA2 triggers a caspase-8–dependent apoptosis. Accordingly, SHetA2 up-regulated DR5 expression, including cell surface levels of DR5, and augmented tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)–induced apoptosis. Importantly, small interfering RNA (siRNA)–mediated blockade of DR5 induction conferred cell resistance to SHetA2-induced apoptosis, as well as SHetA2/TRAIL-induced apoptosis. These results show that DR5 induction is a key component of apoptosis induced by SHetA2 or by SHetA2 combined with TRAIL. SHetA2 exerted CAAT/enhancer-binding protein homologous protein (CHOP)–dependent transactivation of the DR5 promoter. Consistently, SHetA2 induced CHOP expression, which paralleled DR5 up-regulation, whereas siRNA-mediated blockage of CHOP induction prevented DR5 up-regulation, indicating CHOP-dependent DR5 up-regulation by SHetA2. Collectively, we conclude that CHOP-dependent DR5 up-regulation is a key event mediating SHetA2-induced apoptosis. [Cancer Res 2008;68(13):5335–44]
APIXABAN FOLLOWING ACUTE CORONARY SYNDROMES AMONG PATIENTS WITH PRIOR STROKE: INSIGHTS FROM THE APPRAISE-2 TRIAL
Authors: Matthew Sherwood, Renato Lopes, Jie-Lena Sun, Robert Harrington, Lars Wallentin, Daniel T. Laskowitz, Stefan James, Shaun Goodman, Harald Darius, Basil Lewis, Danny Liaw, C. Michael Gibson, John Alexander
Journal: Journal of the American College of Cardiology (2015)
IL-23 produced by CNS-resident cells controls T cell encephalitogenicity during the effector phase of experimental autoimmune encephalomyelitis
Authors: Burkhard Becher, Brigit G. Durell, Randolph J. Noelle
Journal: Journal of Clinical Investigation (2003)

CNS-resident cells, in particular microglia and macrophages, are a source of inflammatory cytokines during inflammation within the CNS. Expression of IL-23, a recently discovered cytokine, has been shown to be critical for the development of experimental autoimmune encephalomyelitis (EAE) in mice. Expression of the p40 subunit of IL-12 and IL-23 by microglia has been shown in situ and in vitro, but direct evidence for a functional significance of p40 expression by CNS cells during an immune response in vivo is still lacking. Here we report that p40 plays a critical role in maintaining encephalitogenicity during the disease course. By using irradiation bone marrow chimeras, we have generated mice in which p40 is deleted from the CNS parenchyma but not the systemic immune compartment. Our studies show that p40 expressed by CNS-endogenous cells is critical for the development of myelin oligodendrocyte glycoprotein–induced EAE. In spite of the reduced clinical disease, the absence of p40 from the CNS has little impact on the degree of inflammation. Expression profiles of the CNS lesions show an increase in Th2 cytokines when compared with mice that develop EAE in the presence of CNS IL-12 and/or IL-23. Taken together, our data demonstrate that p40 expression by CNS-resident cells forms the basis for the Th1 bias of the CNS.
A False Positive I-131 MIBG Due to Dilated Renal Pelvis: A Case Report
Authors: R H BAHAR, S MAHMOUD, A IBRAHIM, A H AL-GAZZAR
Journal: Clinical Nuclear Medicine (1988)

A case of false positive I-131 MIBG imaging for detection of pheochromocytoma is presented. There was an area of increased tracer uptake in the left renal region that showed steadily reducing activity over a period of three days. This raised the suspicion of a dilated renal pelvis, which was later confirmed by Tc-99m DTPA imaging. It is advisable in cases of ambiguous I-131 MIBG imaging to use Tc-99m DTPA rather than Tc-99m DMSA for localizing the kidneys and renal pelvis.
Congenital Heart Disease in 56,109 Births Incidence and Natural History
Authors: S. C. MITCHELL, S. B. KORONES, H. W. BERENDES
Journal: Circulation (1971)

Within a prospective study of 56,109 total births, 457 youngsters have been found to have congenital heart disease. The overall incidence is 8.14/1000 total births, 8.0/1000 for the Negro and 8.3/1000 for the white. A specific lesion has been identified for each patient and lesion frequencies given for each class of patient, stillbirth, neonatal death, infant death, childhood death, and survivors. The percentage of autopsies was 93% in the stillbirths, 89% in the neonatal deaths, and 76% for those dying after 28 days of age. Of those classified as having definite congenital heart disease, 93% have been examined by a pediatric cardiologist. The average follow-up time for the 272 survivors is 3 years. Thirty-five per cent of patients with ventricular septal defect surviving more than 6 months had their lesion close spontaneously; one-half of the survivors with tetralogy of Fallot were "atypical," and essentially equal numbers of blacks and whites had all types of coarctation of the aorta in line with the study population, which is 47% black and 53% white.
Complex dynamics of hepatitis B virus resistance to adefovir
Authors: Coralie Pallier, Christophe Rodriguez, Rozenn Brillet, Patrice Nordmann, Christophe Hézode, Jean‐Michel Pawlotsky
Journal: Hepatology (2008)

In patients with hepatitis B e antigen-negative chronic hepatitis B, adefovir dipivoxil administration selects variants bearing reverse transcriptase rtN236T and/or rtA181V/T substitutions in 29% of cases after 5 years. The aim of this study was to characterize the dynamics of adefovir-resistant variant populations during adefovir monotherapy in order to better understand the molecular mechanisms underlying hepatitis B virus resistance to this class of nucleotide analogues. Patients included in a 240-week clinical trial of adefovir monotherapy who developed adefovir resistance-associated substitutions were studied. The dynamics of hepatitis B virus populations were analyzed over time, after generating nearly 4,000 full-length reverse transcriptase sequences, and compared with the replication kinetics of the virus during therapy. Whatever the viral kinetics pattern, adefovir resistance was characterized by exclusive detection of a dominant wild-type, adefovir-sensitive variant population at baseline and late and gradual selection by adefovir of several coexisting resistant viral populations, defined by the presence of amino acid substitutions at position rt236, position rt181, or both. The gain in fitness of one or the other of these resistant populations during adefovir administration was never associated with the selection of additional amino acid substitutions in the reverse transcriptase. Conclusion: Our results suggest that adefovir administration selects poorly fit preexisting or emerging viral populations with low-level adefovir resistance, which subsequently compete to fill the replication space. Viral kinetics depends on the initial virological response to adefovir. Lamivudine add-on restores some antiviral efficacy, but adefovir-resistant variants remain predominant. Whether these adefovir resistance–associated substitutions may confer cross-resistance to tenofovir in vivo will need to be determined. (HEPATOLOGY 2009;49:50-59.)
Reproducibility of three-dimensional lumen, plaque, and outer vessel reconstructions and of endothelial shear stress measurements in vivo to determine progression of atherosclerosis
Authors: Ahmet U. Coskun, Scott Kinlay, Maureen E. Clark, Milan Sonka, Andreas Wahle, Olusegun J. Ilegbusi, Jeffrey J. Popma, Richard E. Kuntz, Charles L. Feldman, Peter H. Stone
Journal: Journal of the American College of Cardiology (2002)
Coating of stents by autologous vascular grafts reduces the extent of vascular injury in porcine coronary arteries
Authors: K. Toutouzas, C. Stefanadis, E. Tsiamis, S. Vaina, C. Vlachopoulos, N. Giatrakos, E. Papagiorgaki, N. Kostomiteopoulos, P. Toutouzas
Journal: Journal of the American College of Cardiology (1998)
The Consult Guys - NPO Before Surgery: How Long?
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2014)

Web Exclusives18 March 2014The Consult Guys - NPO Before Surgery: How Long?FREEGeno J. Merli, MD, Howard H. Weitz, MDGeno J. Merli, MDSearch for more papers by this author, Howard H. Weitz, MDSearch for more papers by this authorAuthor, Article and Disclosure Informationhttps://doi.org/10.7326/G14-3003 SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The Consult Guys bring a new perspective to the art and science of medicine with lively discussion and analysis of real-world cases and situations.For more videos from and information on The Consult Guys, visit www.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Author, Article and Disclosure InformationAffiliations: Disclosures: Geno J. Merli, MD, reports the following: Research grants/contracts: Bristol-Myers Squibb, Bayer, sanofi-aventis; Consultancies: Bristol-Myers Squibb, Bayer, sanofi-aventis. Howard H. Weitz, MD, reports that he has no financial relationships or interests to disclose. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 March 2014Volume 160, Issue 6Page: CG3KeywordsConflicts of interestResearch grantsResearch reporting guidelinesSurgery ePublished: 18 March 2014 Issue Published: 18 March 2014 CopyrightCopyright © 2014 by American College of Physicians. All Rights Reserved.Loading ...
Gastric rupture and laryngeal mask airway: Authors' reply
Authors: Nathaniel Haslam, John E Duggan
Journal: BMJ (2005)

Electronic data protection: procedures need drastic improvementEditor-Gulena et al are correct to challenge overzealous interpretation of data protection law in their questionnaire survey of patients' and visitors' views about having their names displayed in hospital. 1Measures taken by doctors to safeguard patient confidentiality, especially electronic records, are, however, severely deficient and fuel the concerns of those entrusted to police data security.We invited 32 surgical trainees to complete a questionnaire regarding their Data Protection Act registration and electronic data confidentiality practices.Of 29 responders, 26 trainees regularly computerised and stored patients' data.One person was registered with the Data Protection Act.Only three of 14 desktops, eight of 19 laptops, and three of 14 handheld computers forced a password logon.Sixteen of 29 trainees used the same password for all machines, and 25 of 27 passwords were less than eight characters long.All desktops, 16 of 19 laptops, and five of 14 handhelds were routinely connected to the internet, and half of these had not had their online security settings adjusted.Of 29 trainees, 28 did not encrypt their sensitive data files.Ten trainees had sent patients' data unencrypted over the internet, using a non-secure server.Electronic data confidentiality practices among surgical trainees are unsafe, and this is unlikely to be confined to our study population.A breach in confidentiality would have widespread implications for public trust.][4] Existing passwords should be improved, and biometric logon systems (fingerprint scanning) considered.Files containing sensitive data should be routinely encrypted.Magnetic and solid state computer storage devices (including hard disks, floppy disks, CD Roms, DVD Roms, and memory sticks) should undergo routine physical or electronic data shredding after their final use. 5 We are implementing medical information technology security training for this particu-lar group of doctors and would urge others to initiate similar programmes before a serious breach occurs.
Coconstructed functionality instead of functional normality
Authors: Shu-Chen Li, Ulman Lindenberger
Journal: Behavioral and Brain Sciences (2002)

We agree with the critique of the Residual Normality assumption. Moreover, we challenge monolithic views of functional normality. Throughout life, development and adaptation require variations in cortical functional circuitry within and across individuals. We propose the principle of “coconstructed functionality” which maintains that brain-behavior functional correspondences are dynamically coproduced by neurobiological, experiential, and contextual processes.