tbuckley/cabot-search huggingface dataset:
Amalgamating Oncolytic Viruses to Enhance Their Safety, Consolidate Their Killing Mechanisms, and Accelerate Their Spread
Authors: Camilo Ayala-Breton, Lukkana Suksanpaisan, Emily K Mader, Stephen J Russell, Kah-Whye Peng
Journal: Molecular Therapy (2013)

Oncolytic viruses are structurally and biologically diverse, spreading through tumors and killing them by various mechanisms and with different kinetics. Here, we created a hybrid vesicular stomatitis/measles virus (VSV/MV) that harnesses the safety of oncolytic MV, the speed of VSV, and the tumor killing mechanisms of both viruses. Oncolytic MV targets CD46 and kills by forcing infected cells to fuse with uninfected neighbors, but propagates slowly. VSV spreads rapidly, directly lysing tumor cells, but is neurotoxic and loses oncolytic potency when neuroattenuated by conventional approaches. The hybrid VSV/MV lacks neurotoxicity, replicates rapidly with VSV kinetics, and selectively targets CD46 on tumor cells. Its in vivo performance in a myeloma xenograft model was substantially superior to either MV or widely used recombinant oncolytic VSV-M51.
Monoclonal antibody inhibition of cholesteryl ester transfer protein activity in the rabbit. Effects on lipoprotein composition and high density lipoprotein cholesteryl ester metabolism.
Authors: M E Whitlock, T L Swenson, R Ramakrishnan, M T Leonard, Y L Marcel, R W Milne, A R Tall
Journal: Journal of Clinical Investigation (1989)

Cholesteryl ester transfer protein (CETP) promotes in vitro transfer of cholesteryl ester (CE) and triglyceride (TG) between lipoproteins. We studied the function of CETP in vivo in rabbit lipoprotein metabolism using a neutralizing monoclonal antibody (MAb, TP1) to CETP. Rabbits were injected with TP1 (n = 8), or irrelevant MAb or saline (control, n = 8), resulting in an initial 71% inhibition of CETP, which fell to 45% after 48 h. HDL CE rose in the inhibited animals, reaching levels that doubled initial and control values at 48 h (P less than 0.001). HDL TG fell reciprocally, but HDL protein did not change, suggesting a CE for TG exchange. VLDL CE/TG decreased. Rabbits were also given [3H]cholesteryl ether HDL (a CE analogue). CETP inhibition delayed the initial clearance of radioactivity from HDL (control 6.8 vs. TP1 4.1 pools/d) and plasma (7.8 vs. 5.2 pools/d). We conclude that CETP plays a quantitatively important role in HDL CE catabolism in the rabbit, promoting the exchange of TG for CE and the clearance of CE from plasma.
Resistance Caused by Topical Antibiotics
Authors: Stephan Epstein
Journal: JAMA (1967)

<h3>To the Editor:—</h3> Your editorial, "Neomycin-Resistant Staphylococci in Outpatients" (<b>200</b>:1177, 1967), calls attention to the increasing frequency of resistance to neomycin, apparently following its external (topical) application. Most dermatologists have been mainly concerned with its sensitizing aspects, and therefore some of them now routinely use other antibiotics topically, such as oxytetracycline (Terramycin) which rarely causes contact sensitivity, or erythromycin, which is practically nonsensitizing. It has been thought that topical use of these drugs would not interfere with their later systemic use, but now we must consider the possibility that topical treatment with antibiotics may cause staphylococcal resistance to these drugs. The following case report suggests that resistance to erythromycin also may result from its topical use. <h3>Report of a Case:—</h3> A 76-year-old white man with rosacea complicated by folliculitis started using an erythromycin-containing ointment in September 1963. For four years this medication successfully cleared minor flare-ups. In 1965 the
A Population-Based Study of School Scoliosis Screening
Authors: Barbara P. Yawn
Journal: JAMA (1999)

ContextAlthough school-based screening programs for adolescent idiopathic scoliosis are mandated in 26 states in the United States, few program outcomes data exist regarding the effectiveness of such programs.ObjectiveTo determine the effectiveness of a community-based school scoliosis screening program.Design, Setting, and ParticipantsRetrospective cohort study of children who attended kindergarten or first grade at public or private schools in Rochester, Minn, during 1979-1982. Children were followed up until age 19 years or until they left the school district.Main Outcome MeasuresNumber of children diagnosed and treated for scoliosis, based on results from scoliosis screenings performed annually in grades 5 through 9, linked to community medical records data; performance characteristics of the screening program.ResultsOf the 2242 children screened, 92 (4.1%) were referred for further evaluation. Of these, 68 (74%) had documented medical or chiropractic evaluation of scoliosis. School screening identified 5 of the 9 children treated for scoliosis but resulted in referrals for another 87 children who were not treated. The cumulative incidence of diagnosed scoliosis in this population was 1.8% (95% confidence interval [CI], 1.2%-2.3%) for curves of more than 10°, 1.0% (95% CI, 0.6%-1.5%) for curves of at least 20°, and 0.4% (95% CI, 0.1%-0.6%) for curves of 40° or more; 0.4% (0.5% of girls and 0.3% of boys) were treated for scoliosis. The positive predictive value of the school screening program for the identification of treated scoliosis was 0.05 (95% CI, 0.048-0.052), with 448 children needed to screen to identify 1 child who subsequently received treatment. The percent positive agreement across consecutive years of screening varied from 7% to 30%.ConclusionIn this population, school scoliosis screening identified some children who went on to receive treatment but referred many more who did not. These data should be considered in making decisions regarding school scoliosis screening.
Losartan vs Candesartan for Heart Failure
Authors: Lars H. Lund, Lina Benson
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Adenosine-Induced Long-standing Postischemic Left Ventricular Dysfunction Evaluated With Gated SPECT
Authors: Kyung Ah Chun, Ihn Ho Cho
Journal: Clinical Nuclear Medicine (2004)

This study was performed to determine the after-effects of pharmacologic stress (adenosine) on left ventricular (LV) function-end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (LVEF)-with Tl-201 and Tc-99m MIBI SPECT.A total of 263 patients were grouped according to the time interval between isotope injection and imaging. Group A: within 1 hour (n = 99; men, n = 48; women, n = 51; mean age: 63.2 years), subgrouped as patients with no perfusion defect (NPD; n = 61), reversible defect (RD; n = 33), and fixed defect (FD; n = 5). Group B: 1 to 2 hours (n = 110; men, n = 66; woman, n = 44; mean age, 63 years), NPD (n = 64), RD (n = 26), and FD (n = 20). 3) Group C: 2 to 3 hours (n = 54; men, n = 30; women, n = 24; mean age, 62 years); NPD (n = 22), RD (n = 17), and FD (n = 15). All patients were in sinus rhythm during the study and had no prior history of myocardial infarction.In group A, in the patients with RD, poststress LVEF was significantly depressed after adenosine infusion (53.1 +/- 9.5% vs 58.3 +/- 10.2%, P < 0.001) and showed a wall motion abnormality, which was worse after stress than during rest. The mean difference in LVEF (DeltaLVEF) between rest and stress was 5.2%. The DeltaLVEF in those patients with RD was significantly higher than that in the NPD (0.9%, P < 0.01) or FD (2.1%, P < 0.05) subgroups. Twenty of the 33 patients (60.6%) with RD showed an increase in LVEF > or = 5% from poststress to rest, and the poststress ESV (43.3 +/- 19.0 mL) was significantly higher than the ESV (38.5 +/- 18.4 mL, P < 0.01) at rest, but there was no significant difference in the EDV (90.5 +/- 26.4 vs 89.7 +/- 26.2 mL). In group B, DeltaLVEF was 1.5%, 4.4%, and 1.2% in patients with NPD, RD, and FD respectively. In group C, DeltaLVEF was 2.5%, 3.2%, and 0.9% in patients with NPD, RD, and FD respectively, and there was no significant difference in DeltaLVEF among patients. In group C, 4 of 17 patients (23.5%) with RD showed an increase in LVEF > or = 5% from poststress to rest.These results showed that adenosine stress-induced postischemic LV dysfunction is well noted on early quantitative gated SPECT in patients with RD and can also be observed on delayed gated SPECT, even though the incidence of LV dysfunction is less than that in early gated SPECT.
Atrioventricular Conduction Defects in Patients with Sinus Bradycardia
Authors: ONKAR S. NARULA
Journal: Circulation (1971)

A-V conduction was analyzed in 75 patients (mean age, 73 years) with sinus bradycardia (SB) by His bundle (BH) recordings. Forty-five of these patients had normal QRS complexes (≦0.10 sec) and 30 had abnormal QRS complexes (≧0.12 sec). The conduction times through the atrium (P-A), A-V node (A-H), and His-Purkinje system (H-V) were measured during normal sinus rhythm and transient right atrial pacing up to rates of 150/min. The normal range of conduction times through various regions is: P-A = 25 to 45 msec; A-H = 50 to 120 msec, and H-V = 35 to 45 msec. Overall A-V conduction was completely normal only in 25 (33%) patients. Of these 25 patients, 20 had a narrow QRS complex and five had an abnormal QRS complex. The remaining 50 patients showed abnormal A-V conduction in one or more regions (P-A in 10, A-H in five, BH in six, H-V in 10, and mixed in 19). In some patients despite normal ECGs, the H-V time was abnormal and 1:1 A-V conduction was present during atrial pacing up to 150/min. An abnormal H-V time in association with a normal QRS complex is suggestive of delay in the His bundle. Fourteen patients were restudied at intervals of 6 months to 2 years. Three of these 14 patients showed prolongation of conduction times over 1½ to 2 years. Our data demonstrate that SB is often (67%) associated with A-V conduction abnormalities. A-V conduction was abnormal in 56% of patients with normal and 83% with abnormal QRS complexes. The ECG and atrial pacing are of limited value in assessing A-V conduction. The BH recordings in symptomatic patients with sinus bradycardia may be of clinical significance in the selection of site for pacemaker implantation, that is, atrial or ventricular.
A 3-month evaluation of the efficacy of nedocromil sodium in asthma: A randomized, double-blind, placebo-controlled trial of nedocromil sodium conducted by a Canadian multicenter study group
Authors: A REBUCK, S KESTEN, L BOULET, A CARTIER, D COCKCROFT, J GRUBER, F LABERGE, E LEECHUY, M KESHMIRI, G MACDONALD
Journal: Journal of Allergy and Clinical Immunology (1990)
Increased Plasma Norepinephrine Levels During Prazosin Therapy for Severe Congestive Heart Failure
Authors: Wilson S. Colucci, Gordon H. Williams, Eugene Braunwald
Journal: Annals of Internal Medicine (1980)

To ascertain whether increased sympathetic nervous system activity may contribute to the attenuation of prazosin's effect on congestive heart failure, we measured plasma norepinephrine levels in 10 patients with severe heart failure before and after chronic prazosin therapy. Norcpinephrine levels were increased in eight of 10 patients while supine (145 +/- 133 pg/mL; after, 481 +/- 376 pg/mL; P < 0.01); levels measured in five patients while upright were also increased (before, 351 +/- 238 pg/mL; after, 651 +/- 258 pg/mL; P < 0.05). Left ventricular ejection fraction measured by gated blood pool scan was increased from 16.9% +/- 8.1% to 25.4% +/- 11.3% (N = 10, P < 0.01). Mean systemic blood pressure and heart rate were unchanged. Increased plasma norepinephrine levels may attenuate prazosin's vasodilator action in heart failure. The cause of the increase in norepinephrine levels is unclear and warrants further study.
Heme Oxygenase 1 Determines Atherosclerotic Lesion Progression Into a Vulnerable Plaque
Authors: Caroline Cheng, Annemarie M. Noordeloos, Viktoria Jeney, Miguel P. Soares, Frans Moll, Gerard Pasterkamp, Patrick W. Serruys, Henricus J. Duckers
Journal: Circulation (2009)

The molecular regulation for the transition from stable to vulnerable plaque remains to be elucidated. Heme oxygenase 1 (HO-1) and its metabolites have been implicated in the cytoprotective defense against oxidative injury in atherogenesis. In this study, we sought to assess the role of HO-1 in the progression toward plaque instability in carotid artery disease in patients and in a murine model of vulnerable plaque development.Atherectomy biopsy from 112 patients with clinical carotid artery disease was collected and stratified according to characteristics of plaque vulnerability. HO-1 expression correlated closely with features of vulnerable human atheromatous plaque (P<0.005), including macrophage and lipid accumulation, and was inversely correlated with intraplaque vascular smooth muscle cells and collagen deposition. HO-1 expression levels correlated with the plaque destabilizing factors matrix metalloproteinase-9, interleukin-8, and interleukin-6. Likewise, in a vulnerable plaque model using apolipoprotein E(-/-) mice, HO-1 expression was upregulated in vulnerable versus stable lesions. HO-1 induction by cobalt protoporphyrin impeded lesion progression into vulnerable plaques, indicated by a reduction in necrotic core size and intraplaque lipid accumulation, whereas cap thickness and vascular smooth muscle cells were increased. In contrast, inhibition of HO-1 by zinc protoporphyrin augmented plaque vulnerability. Plaque stabilizing was prominent after adenoviral transduction of HO-1 compared with sham virus-treated animals, providing proof that the observed effects on plaque vulnerability were HO-1 specific.Here we demonstrate in a well-defined patient group and a murine vulnerable plaque model that HO-1 induction reverses plaque progression from a vulnerable plaque to a more stable phenotype as part of a compensatory atheroprotective response.
Latent Gonorrhea in Women
Authors: LeMon Clark
Journal: JAMA (1969)

<h3>To the Editor:—</h3> In QUESTIONS AND ANSWERS (<b>208</b>:1029, 1969), Evalyn S. Gendel answers a query about conjugal gonorrhea. Her answer may be amplified. Some time ago, a young man with gonorrhea was very upset saying, "Well, my wife has been cheating on me because I have been married to her six months and have had intercourse with no one but her." I asked to have his wife come to see me. Examination of the cervix revealed it to be quite clean with no evidence of infection. Massage of the urethra produced a minute drop of pus which when stained revealed gonococci. She had been married previously, had divorced her previous husband a year earlier because of infidelity. She had had some burning and a little discomfort in the vagina at the time of urination for several weeks. She undoubtedly had gonorrhea. Vaginal and cervical infection resolved, but that of
Phosphorylcholine-Targeting Immunization Reduces Atherosclerosis
Authors: Giuseppina Caligiuri, Jamila Khallou-Laschet, Marta Vandaele, Anh-Thu Gaston, Sandrine Delignat, Chantal Mandet, Heinz V. Kohler, Srini V. Kaveri, Antonino Nicoletti
Journal: Journal of the American College of Cardiology (2007)
Prognostic Implications of Warfarin Cessation After Major Trauma
Authors: Daniel G. Hackam, Alexander Kopp, Donald A. Redelmeier
Journal: Circulation (2005)

Warfarin therapy is often withheld from elderly patients who fall or otherwise experience injury because of concerns regarding the long-term risk of hemorrhage in these individuals. We studied whether stopping warfarin after trauma is associated with a higher risk of subsequent adverse cardiovascular events.We conducted a retrospective, population-based, cohort study using linked administrative databases in the province of Ontario, Canada for the years 1992 to 2001. A total of 8450 elderly patients (age >65 years) who survived an incident of major trauma and were receiving warfarin before injury were followed up for a mean of 3.3 years. During the 6-month interval after trauma, 1827 (22%) patients discontinued warfarin, whereas 6623 (78%) patients continued warfarin. Warfarin cessation was not associated with an increased risk of subsequent stroke (hazard ratio [HR] 0.99, 95% CI 0.82 to 1.21) or myocardial infarction (HR 0.94, 95% CI 0.74 to 1.20) but was associated with a lower risk of major hemorrhage (HR 0.69, 95% CI 0.54 to 0.88) and a higher risk of venous thromboembolism (HR 1.59, 95% CI 1.07 to 2.36). Adjustment for baseline demographics, stroke risk factors, other comorbidities, and characteristics of the trauma did not materially change these findings. On-treatment analyses yielded similar results.Cessation of warfarin in elderly patients after major trauma was not associated with an increased risk of arterial thrombotic events but was associated with a significantly increased risk of venous thromboembolism.
Myocardial Infarction in Parents Who Lost a Child
Authors: Jiong Li, Dorthe Hansen, Preben Bo Mortensen, Jørn Olsen
Journal: Circulation (2002)

The association between psychological stress and coronary heart disease remains unclear. We conducted a prospective follow-up study based on national registers to investigate if the death of a child, one of the most severe stressors, increases the risk of myocardial infarction (MI) in parents.From 1980 to 1996, 19 361 parents who lost a child (<18 years of age) in Denmark were recruited to the exposed cohort, and 295 540 parents matched on family structure were selected for the unexposed cohort. The Cox proportional hazards model was used to evaluate the relative risk (RR) of myocardial infarction (MI). The average RRs for a fatal MI and any first MI among the exposed were 1.36 (95% CI, 0.98 to 1.88) and 1.28 (95% CI, 1.08 to 1.51), respectively. The two cohorts had similar MI risk during the first 6 years of follow-up. From the 7th to the 17th year of follow-up, the exposed cohort had a RR of 1.58 (95% CI, 1.08 to 2.30) for fatal MI and a RR of 1.31 (95% CI, 1.09 to 1.57) for first MI. Parents who lost a child unexpectedly, especially from sudden infant death syndrome, experienced higher RRs.The death of a child was associated with an increased risk of MI in bereaved parents.
Three-Dimensional Reconstruction of the Rabbit Atrioventricular Conduction Axis by Combining Histological, Desmin, and Connexin Mapping Data
Authors: Yu-Shien Ko, Hung-I Yeh, Yu-Lin Ko, Yu-Chun Hsu, Chin-Fen Chen, Semon Wu, Ying-Shiung Lee, Nicholas J. Severs
Journal: Circulation (2004)

The 3D structure of the atrioventricular conduction axis incorporating detailed cellular and molecular composition, especially that relating to gap-junctional proteins, is still unclear, impeding mechanistic understanding of cardiac rhythmic disorders.A 3D model of the rabbit atrioventricular conduction axis was reconstructed by combining histological and immunofluorescence staining on serial sections. The exact cellular boundaries, especially those between transitional cells and atrial myocardium, were demarcated by a dense and irregular desmin-labeling pattern in conductive myocardium. The model demonstrates that the atrioventricular conduction axis is segregated into 2 connecting compartments, 1 predominantly expressing connexin45 (compact node and transitional cells) and the other predominantly coexpressing connexin43 and connexin45 (His bundle, lower nodal cells, and posterior nodal extension). The transitional zone shows unique features of spatial complexity, including a bridging bilayer structure (a deep transitional zone connecting with a superficial atrial-transitional overlay) and asymmetrical continuity (wider atrial-transitional interfaces and shorter atrial-axial distances in the hisian portion than in the ostial portion). In the latter compartment, the His bundle, lower nodal cells, and posterior nodal extension form a continual axis and longitudinal transitional-axial interface.Key findings of the present study are the demonstration of a distinct anatomical border between transitional and atrial cells, connection between transitional cells and both lower nodal cells and posterior nodal extension, and distinctive connexin expression patterns in different compartments of the rabbit atrioventricular conduction axis. These features, synthesized in a novel 3D model, provide a structural framework for the interpretation of nodal function.
Autoimmunity: Present Concepts
Authors: C. R. STILLER
Journal: Annals of Internal Medicine (1975)

Autoimmune disease may be effected by humoral mechanisms (direct antibody effect or pathogenic antigen-antibody complexes), cell-mediated mechanisms, and possibly complement in the absence of antibody. In view of recent work, self-tolerance can no longer be explained by the clonal selection theory; cells that are capable of recognizing self-antigens and effecting an autoimmune response seem to be present in the normal individual but actively regulated by a process involving antigen-antibody complexes or suppressor T cells. The determination that a clinical state is an autoimmune disease cannot, therefore, be made only on the basis of the presence of autoantibody as this may be part of the normal and active state of immunoregulation of autoimmunity. Indeed, the absence of autoantibody may be the immunodeficient state that allows a full-blown autoimmune disease to occur. In view of this knowledge, the basis for the diagnosis of autoimmune disease and the rationale for treatment based on the objective of inhibiting all immune responses to the autoantigen require re-examination.
Organisation/Outcome/Scoring
Authors: Fan Xun-mei, Lu Zhong-yi, Deniz Anadol, Serap Çamur, Ramazan Öztűrk, Ayşe Korkmaz, Imran Özalp, Minke E. van der Wal, Reinoud J. B. J. Gemke, A. Johannes van Vught, A. Sarti, A. R. De Gaudio, M. Calamandrei, P. Martinelli, M. Cavuta, L. B. Faulkner, P. Busoni, M. Verma, J. Chhatwal, L. E. Wilson, B. Habibi, S. Nadel, P. Habibi, C. Vasconcelos, L. Ventura, I. Fernandes, R. Valente, A. Marques, D. Barata, A. Burguet, A. Menget, E. Monnet, J. Jacquin, C. Fromentin, H. Allemand, J. Y. Pauchard, M. L. Dalphin, I. A. von Rosenstiel, W. B. Vreede, Carl G. M. Weigle, Mary B. Zollo, Peter Tarczy-Hornoch, I. David Todres, Jon M. Courand, Frank Shann, Tony Slater, Gale Pearson, E. Mora, J. Casado Flores, J. García Pérez, N. González Bravo, M. Monleón, A. Serrano, R. P. G. M. Bijlmer, E. Werner, J. M. Treluyer, B. Zimmermann, Ph. Hubert, M. Cloup, Pedro Celiny Garcia, Eneida Mendonça, Paulo Einloft, Delio Kipper, Jefferson Piva, Renato Fiori, Anjum Hashmi, Sajid Maqbool, M. Idris Mazhar
Journal: Intensive Care Medicine (1996)
Campaign to revitalise academic medicine: Funding needs to be on the discussion table
Authors: Fernando Elijovich
Journal: BMJ (2004)

EDITOR—I was disappointed at the statement in Tugwell's editorial on the campaign to revitalise academic medicine that deals with how to tackle current failures.1 He mentions working within current economic constraints and giving preference to strategies that call for no additional funding.

A false entrepreneurial approach, in which the output …