tbuckley/cabot-search huggingface dataset:
Problems Involved in Prevention of Bacterial Complications of Measles
Authors: G. I. Watson
Journal: BMJ (1955)

Sterile protection against malaria infection can be achieved through vaccination of mice and humans with whole <i>Plasmodium spp.</i> parasites. One such method, known as infection–treatment–vaccination (ITV), involves immunization with wild type sporozoites (spz) under drug coverage. In this work, we used the different effects of antimalarial drugs chloroquine (CQ) and artesunate (AS) on blood stage (BS) parasites to dissect the stage-specific immune responses in mice immunized with <i>Plasmodium yoelii</i> spz under either drug, as well as their ability to protect mice against challenge with spz or infected RBCs (iRBCs). Whereas CQ-ITV induced sterile protection against challenge with both spz and iRBCs, AS-ITV only induced sterile protection against spz challenge. Importantly, AS-ITV delayed the onset of BS infection, indicating that both regimens induced cross-stage immunity. Moreover, both CQ- and AS-ITV induced CD8<sup>+</sup> T cells in the liver that eliminated malaria-infected hepatocytes in vitro, as well as Abs that recognized pre-erythrocytic parasites. Sera from both groups of mice inhibited spz invasion of hepatocytes in vitro, but only CQ-ITV induced high levels of anti-BS Abs. Finally, passive transfer of sera from CQ-ITV–treated mice delayed the onset of erythrocytic infection in the majority of mice challenged with <i>P. yoelii</i> iRBCs. Besides constituting the first characterization, to our knowledge, of AS-ITV as a vaccination strategy, our data show that ITV strategies that lead to subtle differences in the persistence of parasites in the blood enable the characterization of the resulting immune responses, which will contribute to future research in vaccine design and malaria interventions.
Genetic Disease. Diagnosis and Treatment.
Authors: Alan Emery
Journal: Annals of Internal Medicine (1983)

There can be many problems with publishing the proceedings of a conference.There may be repetition and overlap between different contributors, and, either because not all participants could be dragooned into producing a script or the editor was not sufficiently ruthless and authoritarian, the final result can be patchy.Further, because of constraints imposed by space if the individual subjects to be covered are at all extensive, their treatment may be either superficial or so dense as to be almost incomprehensible.Finally, publication is often delayed because not all contributors are equally punctilious.Regrettably, some of these critcisms can also be leveled at this, the edited proceedings of the Fifth Beckman Conference in Clinical Chemistry, which was held in Monterey in 1981.It is redeemed, however, by the fact that the subject, the diagnosis and treatment of genetic disease, is an important one, and all the contributors are internationally recognized and therefore write with authority.The book is divided into five parts, each with three chapters: perspectives (principles of human genetics, legal problems, cytogenetic abnormalities in mental retardation), clinical diagnosis (Tay-Sachs disease, cancer susceptibility, genetics of endocrinological
Abstract 1124: CD40L Induces Inflammation in Adipose Tissue - a Potential Link Between the Metabolic Syndrome and Atherosclerosis
Authors: Anna Missiou, Isabel Platzer, Sandra Ernst, Uwe Schonbeck, Peter Libby, Christoph Bode, Andreas Zirlik
Journal: Circulation (2007)

Background: CD40L figures prominently as marker and mediator of atherosclerosis and its clinical complications. Recent data also demonstrate an association between CD40L and the metabolic syndrome. In the light of these data we hypothesized a functional pro-inflammatory role of CD40L in adipose tissue that provokes systemic pro-inflammatory responses and potentially mediates some of the high cardiovascular risk associated with the metabolic syndrome. Methods and Results: Adipocytes and preadipocytes isolated from adipose tissue obtained from bariatic surgery did not express CD40L but its receptor CD40 as assessed by PCR and immunohistochemistry. Furthermore, sections of human adipose tissue from obese donors contained more macrophages and T cells colocalizing with CD40L than those from lean controls. Stimulation of both adipocytes and preadipocytes with recombinant CD40L resulted in a concentration- and time-dependent release of the pro-inflammatory cytokine IL-6, the chemokines MCP -1 and IL-8 as well as the inhibitor of fibrinolysis PAI-1 into the supernatant as quantified by ELISA. Membranes isolated from a Murine cell line overexpressing human CD40L reproduced these pro-inflammatory effects compared to respective controls. Interestingly, fenofibrate but neither rosiglitazone, metformin, nor atorvastatin attenuated the CD40L-inducible expression of these pro-atherogenic mediators. Finally, supernatants from adipocytes and preadipocytes stimulated with CD40L activated endothelial cells and macrophages, typical cell types resident in atherosclerotic lesions, as assessed by FACS for tissue factor, Mac-1, and ICAM-1, respectively. Conclusions: Our data suggest that CD40L induces inflammatory cytokine production in adipose tissue resulting in activation of endothelial cells and macrophages. This new mechanism may contribute to the high cardiovascular risk of patients suffering from the metabolic syndrome.
Abstract 5422: Effect of Age on Expression of AT1 and AT2 Receptors and ACE-2, Angiotensin (1-7), Ac-SDKP and Smad-2 Proteins After Acute Reperfused ST-Segment Elevation Myocardial Infarction
Authors: Arivazhagan Palaniyappan, Halliday Idikio, Bodh I Jugdutt
Journal: Circulation (2008)
Abstract 16080: Chronic Akt Blockade Aggravates Pathological Hypertrophy and Inhibits Physiological Hypertrophy
Authors: Johannes H Riffel, Sebastian J Buss, Marco Hagenm̈uller, Celine Weiss, Hugo A Katus, Stefan E Hardt
Journal: Circulation (2010)

Background: Attenuation of adverse myocardial remodeling contributes to improved prognosis after pathological injury of the heart. Activation of Akt in the heart seems to exert positive or negative effects on cardiac function depending on the stimulus which leads to its activation. Here, we investigated the effect of chronic Akt blockade by Deguelin (DEG) on myocardial remodeling and the development of hypertrophy following a pathological stimulus (myocardial infarction and aortic banding) and following exercise training (controlled treadmill running). Methods: Wistar rats were orally treated with DEG (4.0 mg/kg) for 4 weeks starting one day after induction of myocardial infarction (MI) or aortic banding. Exercise animals received DEG for 4 weeks during the training period. Results: DEG treatment leads to a significant reduction of phosphorylation of Akt in all groups. 4 weeks after MI, DEG treated animals showed impaired LV function with enhanced LVEDD (12±0,3mm vs 11.1±0,4mm, p<0.05), EDV (439±8μl vs 38...
Abstract 11387: Dose Angiotensin II Receptor Blocker Have Adverse Effects on Coronary Collateral Function After Drug-Eluting Stent Implantation in Hypertensive Patients?
Authors: Nobuyoshi Tanaka, Mitsuyasu Terashima, Hitoshi Matsuo, Tsuyoshi Itoh, Maoto Habara, Kenya Nasu, Masashi Kimura, Tatsuya Itoh, Yoshihisa Kinoshita, Mariko Ehara, Etsuo Tsuchikane, Keiko Asakura, Yasushi Asakura, Osamu Katoh, Takahiko Suzuki
Journal: Circulation (2010)

Background: Drug-eluting stents (DES) were reported to have an inhibitory effect on coronary collateral growth. Furthermore, there is a concern that this adverse effect would be enhanced by angiote...
Abstract 3172: Impact of Prosthesis-Patient Mismatch on Long-Term Survival After Aortic Valve Replacement
Authors: Dania Mohty, Jean G. Dumesnil, Najmeddine Echahidi, Patrick Mathieu, François Dagenais, Pierre Voisine, Philippe Pibarot
Journal: Circulation (2007)

Background: We recently reported that Prosthesis-Patient Mismatch (PPM) is an independent predictor of operative mortality in patients undergoing aortic valve replacement (AVR). The objective of this study was to evaluate the impact of PPM on late postoperative survival. Methods and Results: Between 1992 and 2005, 2653 patients (age: 68±10 years; 61% of males) underwent AVR in our institution. Patients who died at the time of operation or within 30 days were excluded from this study. The projected indexed effective orifice area (EOAi) was derived from the published normal in vivo EOA values for each model and size of prosthesis and PPM was classified as severe if the EOAi was ≤0.65 cm 2 /m 2 , moderate if it was &gt; 0.65 cm 2 /m 2 and ≤ 0.85 cm 2 /m 2 , or not clinically significant if &gt;0.85 cm 2 /m 2 . PPM was severe in 40 patients (2%), moderate in 797 (31%), and not significant in 1739 (67%). Patients with severe PPM had higher proportion of female gender (67% vs. 38%; P=0.0002) and hypertension (68% vs. 55%, p=0.02) and larger body surface (1.86±0.25 vs. 1.77±0.20, p=0.02). For patients with severe PPM, 5-year survival rate (74±8%) and 10-year survival rate (40±10%) were significantly (p=0.008) less than for patients with moderate PPM (5-yr: 81±2% and 10-yr: 57±3%) or no significant PPM (5-yr: 84±1% and 10-yr: 61±2%). On multivariate analysis after adjustment for other predictors of outcome, severe PPM was associated with increased overall mortality (Hazard ratio 1.38, [95% Confidence Interval 1.04 –1.75]; (p=0.02) Conclusion: In our previous study, we reported that severe PPM is a powerful risk factor for operative mortality. The results of the present study now suggest that severe PPM is also an independent predictor of long-term mortality. Hence, for the patients who are identified to be at risk of severe PPM at the time of operation, every effort should be made to implant a prosthesis with a larger EOA. Funded by: Canadian Institutes of Health Research
Abstract 19599: Survival in High Risk Patients with Severe Aortic Stenosis: Intervention versus Surgery versus Medical Therapy
Authors: Sabine Bleiziffer, Julia Socha, Hendrik Ruge, Matthias Kornek, Gernot Brockmann, Andrea Hutter, Anke Opitz, Nicolo Piazza, Robert Bauernschmitt, Rudiger Lange
Journal: Circulation (2010)
State Leadership in Health Care Transformation
Authors: Ann Hwang, Joshua M. Sharfstein, Christopher F. Koller
Journal: JAMA (2015)

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
Abstract 18314: Dysfunction of Junctional NCX Following JPH2 Knockdown Alters Spatial Properties of Ca2+ Sparks and Contributes to Arrhythmogenesis in Mice
Authors: Wei Wang, Sayali Dixit, Qiongling Wang, Ralph J van Oort, Alejandro Garbino, Andrew P Landstrom, Michael J Ackerman, Xander H Wehrens
Journal: Circulation (2011)

Background. Na+/Ca2+ exchanger (NCX) is essential in tuning intracellular Ca2+ and the development of heart failure (HF). We reported that loss of Junctophilin 2 (JPH2) in adult mouse hearts leads ...
Abstract 496: Increased Trans-Sarcolemmal Calcium Flux and Myofilament Responsiveness in Mice With Cardiomyocyte-Specific Deletion of the Serca2 Gene
Authors: William E Louch, Jon A Birkeland, Kristin B Andersson, Ivar Sjaastad, Halvor K Mork, Ole M Sejersted, Geir Christensen
Journal: Circulation (2007)
Abstract P14: Estradiol Does Not Improve Survival and Hemodynamic Parameters in Male Piglets after Hemorrhage and Ventricular Fibrillation
Authors: Egidijus Semenas, Lars Wiklund
Journal: Circulation (2008)

Introduction: Gender differences in organ functions and survival have been described in animal models of trauma and hemorrhagic shock. The female gender is associated with better cardiac, hepatic and immune functions compared to males after hemorrhagic shock. However, data about gender differences in hypovolemic normothermic cardiac arrest is lacking. Hypothesis: We hypothesized that the estradiol given during cardiopulmonary resuscitation (CPR) will improve survival and hemodynamic response in hypovolemic cardiac arrest and subsequent CPR. Methods: Twenty anesthetized male piglets (with a weight of 25.7 ± 1.7 kg [mean ± SD]) were bled 30% via the right femoral artery to a mean arterial blood pressure of 35 mm during 15 minutes. In the end of bleeding period estradiol group (n=10) received 17â-estradiol 50 ìg/kg intravenously, while the control group received no estradiol (n=10). Later all piglets were subjected to 4 min of untreated ventricular fibrillation followed by up to 15 min of open chest CPR. At 5 min of cardiac arrest piglets received vasopressin 0.4 U/kg, amiodarone 0.5 mg/kg, and hypertonic-hyperoncotic solution 3 ml/kg infusion for 20 minutes. Internal defibrillation was attempted from 8 min of cardiac arrest to achieve restoration of spontaneous circulation (ROSC). The experiment was terminated at 3 hours after initial resuscitation. Data were analyzed using Fisher’s exact test, Kaplan-Meier and repeated measures ANOVA methods. Results: All piglets were successfully resuscitated. No significant differences were observed in survival between the groups (p=0.24). All piglets needed dobutamine infusion and no differences were observed in either total dobutamin dose, or infusion start time (p=0.05). No significant changes were observed in any hemodynamic parameters (p&gt;0.05). Troponin I levels did not differ between groups (p&gt;0.75). Conclusions: Intravenous 17â-estradiol does not improve survival and hemodynamic parameters in male piglets after experimental hypovolemic cardiac arrest.
Tolerability assessment of urasil-tegafur (UFT)/folinic acid (FA) as concurrent chemoradiation (CRT) in adjuvant rectal cancer treatment
Authors: B. M. Atasoy, U. Abacioglu, Z. Ozgen, F. Dane, F. Yumuk, Z. Akgun, S. Ozden, A. Mayadagli, S. Turhal, M. Sengoz
Journal: Journal of Clinical Oncology (2006)

13559 Background: The objective of the present phase II study was to evaluate the feasibility of UFT and FA as a concomittant CRT administration for rectal cancer in the adjuvant setting. Methods: Between October 2003 and December 2005 thirty-one (10 female; 21 male) patients were treated. All the patients were locally advanced (T2N1–2M0 (2), T3N0M0 (12), T3–4N1M0 (9), T3–4N2M0 (7)) and median age was 62 (range, 21–85). Inclusion criteria were WHO 0–1, age ≥ 18, complete tumor resection, stage T3/4 or N+, adequate CBC, liver function tests and signed informed consent form. RT was performed in 8 weeks following the surgery and the dose was 50.4 Gy given at 1.8 Gy daily. Chemotherapy consisted of UFT (300 mg/m 2 /day) and FA (30 mg/day) during week-days of radiotherapy and continued 4 cycles with same dose (D1–28/35days) after CRT. Acute toxicity was assessed according to CTC 2.0 criteria. Results: Median follow-up for all patients was 12 months (between 3–27 months). No toxic death occurred. CRT related side effects were diarrhea Gr 2 (25%) and Gr 3 (25%); emesis Gr 2 (29%) and Gr 3 (10%); dysuria Gr 2 (10%) and Gr 3 (10%). All patients completed radiotherapy but 21 out of 31 (67%) continued with UFT/LV until the end of concurrent treatment. The full compliance to the adjuvant CT part was 63%. During the adjuvant CT period there were diarrhea Gr 3–4 (10%), emesis Gr 3 (10%) and no Gr 3–4 hematological toxicity observed during the whole treatment. During the study period none of the patients failed locally, 3 patients developed distant metastases (2 liver, 1 bone), and 3 patients died (1 with disease, 2 without). Two-year disease-free and overall survival rates were 84% and 71%, respectively. Conclusion: The acute and subacute toxicity of CRT with UFT/LV is acceptable and seems comparable to infusional 5-FU based combined modality treatments. No significant financial relationships to disclose.
Methotrexate in Rheumatoid Arthritis
Authors: Jerzy Swierkot, Jacek Szechiński
Journal: Annals of Internal Medicine (1987)

A variety of disease-modifying antirheumatic drugs (DMARDs) are available to control the clinical activity of rheumatoid arthritis (RA). Methotrexate (MTX), an analogue of folic acid and of aminopterin, is the most commonly used DMARD and is now prescribed worldwide to at least 500,000 patients with RA. The mechanism by which MTX used at a low dose modulates inflammation in RA is still unknown. Monitoring of the therapy in terms of MTX concentration in patients with RA seems not to have a significant influence on the effectiveness of the treatment. Two meta-analyses showed that MTX has one of the best efficacy/toxicity ratios. It should be the first DMARD used in the majority of patients with RA at this time. However, a significant number of patients treated only with MTX fail to achieve optimal disease control, so there are many combinations of DMARD regimes. It is hoped that more aggressive use of conventional DMARDs and biological agents will result in less disability and a higher proportion of patients achieving remission. The therapy of RA is a dynamic process and requires maintaining a delicate balance between benefits and risks. Even with the newer biological agents, MTX continues to serve as a reference point and there is still a role for MTX in the treatment of RA patients.
Abstract 2371: Mean Platelet Volume and Prevalence of Peripheral Artery Disease
Authors: Jeffrey S Berger, Luis H Eraso, Dawei Xie, Daohang Sha, Emile R Mohler
Journal: Circulation (2009)

Introduction: Platelets play a pivotal role in the pathogenesis of atherosclerosis and peripheral artery disease (PAD). Mean platelet volume (MPV), a measure of platelet size available in every blo...
Mechanisms of resistance to EGFR tyrosine kinase inhibitors
Authors: Lihua Huang, Liwu Fu
Journal: Acta Pharmaceutica Sinica B (2015)

Since the discovery that non-small cell lung cancer (NSCLC) is driven by epidermal growth factor receptor (EGFR) mutations, the EGFR tyrosine kinase inhibitors (EGFR-TKIs, e.g., gefitinib and elrotinib) have been effectively used for clinical treatment. However, patients eventually develop drug resistance. Resistance to EGFR-TKIs is inevitable due to various mechanisms, such as the secondary mutation (T790M), activation of alternative pathways (c-Met, HGF, AXL), aberrance of the downstream pathways (K-RAS mutations, loss of PTEN), impairment of the EGFR-TKIs-mediated apoptosis pathway (BCL2-like 11/BIM deletion polymorphism), histologic transformation, ATP binding cassette (ABC) transporter effusion, etc. Here we review and summarize the known resistant mechanisms to EGFR-TKIs and provide potential targets for development of new therapeutic strategies.
Pre-Transplant Remission Status and Peripheral Blood Stem Cell Graft Contribute To Long-Term Outcome After Myeloablative Sibling-Donor Allogeneic Transplant For Multiple Myeloma
Authors: Imran Ahmad, Sandra Cohen, Silvy Lachance, Guy Sauvageau, Denis-Claude Roy, Lambert Busque, Thomas Kiss, Jean-Sebastien Delisle, Lea Bernard, Richard LeBlanc, Jean Roy
Journal: Blood (2013)
Safety of lenalidomide (LEN) from a randomized phase III trial (MDS-004) in low-/int-1-risk myelodysplastic syndromes (MDS) with a del(5q) abnormality.
Authors: P. Fenaux, A. Giagounidis, D. L. Selleslag, O. Beyne-Rauzy, M. Mittelman, P. Muus, R. D. Knight, T. Fu, E. Hellstrom-Lindberg
Journal: Journal of Clinical Oncology (2010)

6598 Background: In a multicenter placebo-controlled study, LEN (10 mg/day for 1–21 days or 5 mg/day for 1–28 days; 28-day cycle) achieved significant RBC transfusion independence for ≥ 26 wks (56% and 41%) and cytogenetic responses (41% and 17%) in RBC transfusion-dependent patients (pts) with Low-/Int-1-risk MDS with del(5q). The most common grade (G) 3–4 adverse events (AEs) were neutropenia and thrombocytopenia. Here, we describe the frequency, timing and management of LEN-associated hematologic AEs. Methods: AEs (NCI CTCAE v3) occurring during the 1 y double-blind phase are summarized. Dose reductions were required for G4 neutropenia or thrombocytopenia by protocol; G-CSF/GM-CSF use was allowed. Results: All 138 pts randomized to LEN (10 mg = 69, 5 mg = 69) who received ≥ 1 dose were included. Median (range) exposure duration in wks was 50 (1–56) for LEN 10 mg and 18 (2–53) for LEN 5 mg (higher response rate with 10 mg explaining longer exposure). In the LEN 10 mg group G3–4 neutropenia was most common in cycles 1 (45%) and 2 (46%), decreasing with additional cycles (29%, 29%, 11%, 7% for cycles 3–6). G3–4 thrombocytopenia rates were 28%, 27%, 12%, 10%, 13%, and 2% in cycles 1–6. A similar trend was reported with LEN 5 mg: neutropenia (cycles 1–6: 46%, 47%, 25%, 22%, 11%, 15%) and thrombocytopenia (cycles 1–6: 19%, 19%, 14%, 8%, 2%, 6%). Other G3–4 AEs included infection (10 mg: 12%; 5 mg: 9%), urosepsis (5 mg: 1%) and febrile neutropenia (10 mg: 1%; 5 mg: 3%); no G3–4 bleeding was reported. Hematologic AEs requiring dose reduction included neutropenia (10 mg: 38%; 5 mg: 28%), thrombocytopenia (10 mg: 23%; 5 mg: 12%) and febrile neutropenia (5 mg: 3%). Those requiring discontinuation were anemia (5 mg: 1%), neutropenia (10 mg: 1%; 5 mg: 6%) and hemophagocytic syndrome (10 mg: 1%). G-CSF/GM-CSF use in LEN 10 and 5 mg groups was comparable (64% and 61%). Conclusions: LEN has a predictable, manageable safety profile; most AEs occurred early and were comparable between 10 and 5 mg. The risk/benefit profile supports 10 mg as starting dose. Anticipation of LEN-associated hematologic AEs, and use of dose modifications and supportive care as needed, should help achieve optimal clinical benefit from LEN. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene Celgene Celgene Amgen, Celgene, Cepahlon, Johnson & Johnson, Merck, Novartis, Roche Amgen, Celgene, Roche
Abstract 16183: High Long-Term Retention Rate of Hands-Only Cardiopulmonary Resuscitation Skill Achieved by Audio-Visual-Practice Reinforcement: A Randomized Placebo Controlled Clinical Trial
Authors: Yimin Xu, Jia Li, Peng Yue, Yahong Xu, Ming Guo, Yan Zhang, Yanling Wang, Fangqin Wu, Shu Zhang, Ying Wu
Journal: Circulation (2013)

Objective: Adequate bystander CPR skill especially high quality chest compression (CC) is vital for providing effective resuscitation of out of hospital cardiac arrest (OHCA), however survival rate...