tbuckley/cabot-search huggingface dataset:
Effect of Tilarginine Acetate in Patients With Acute Myocardial Infarction and Cardiogenic Shock
Authors: None The TRIUMPH Investigators*
Journal: JAMA (2007)

ContextCardiogenic shock complicating acute myocardial infarction (MI) remains a common and lethal disorder despite aggressive use of early revascularization. Systemic inflammation, including expression of inducible nitric oxide synthase (NOS) and generation of excess nitric oxide, is believed to contribute to the pathogenesis and inappropriate vasodilatation of persistent cardiogenic shock. Preliminary, single-center studies suggested a beneficial effect of NOS inhibition on hemodynamics, renal function, and survival in patients with cardiogenic shock.ObjectiveTo examine the effects of an isoform-nonselective NOS inhibitor in patients with MI and refractory cardiogenic shock despite establishment of an open infarct artery.Design, Setting, and PatientsInternational, multicenter, randomized, double-blind, placebo-controlled trial (Tilarginine Acetate Injection in a Randomized International Study in Unstable MI Patients With Cardiogenic Shock [TRIUMPH]) with planned enrollment of 658 patients at 130 centers. Participants were enrolled between January 2005 and August 2006 when the study was terminated early.InterventionTilarginine (L-NG-monomethylarginine [L-NMMA]), 1-mg/kg bolus and 1-mg/kg per hour 5-hour infusion, vs matching placebo.Main Outcome MeasuresThe primary outcome was 30-day all-cause mortality among patients who received study medication. Secondary outcomes included shock resolution and duration, New York Heart Association (NYHA) functional class at 30 days, and 6-month mortality.ResultsEnrollment was terminated at 398 patients based on a prespecified futility analysis. Six-month follow-up was completed in February 2007. There was no difference in 30-day all-cause mortality between patients who received tilarginine (97/201 [48%]) vs placebo (76/180 [42%]) (risk ratio, 1.14; 95% confidence interval, 0.92-1.41; P = .24). Resolution of shock (133/201 [66%] tilarginine vs 110/180 [61%] placebo; P = .31) and duration of shock (median, 156 [interquartile range, 78-759] hours tilarginine vs 190 [100-759] placebo; P = .16) were similar. At 30 days a similar percentage of patients had heart failure (48% tilarginine vs 51% placebo; P = .51) with a similar percentage of those patients in NYHA class I/II (73% tilarginine vs 75% placebo; P = .27). After 6 months mortality rates were similar in the 2 groups (58% tilarginine vs 59% placebo; hazard ratio, 1.04; 95% confidence interval, 0.79-1.36; P = .80).ConclusionsTilarginine, 1-mg/kg bolus and 5-hour infusion, did not reduce mortality rates in patients with refractory cardiogenic shock complicating MI despite an open infarct artery. Early mortality rates in this patient group are high. Further research is needed to develop effective therapies for patients with cardiogenic shock following acute MI.Trial Registrationclinicaltrials.gov Identifier: NCT00112281Published online March 26, 2007 (doi:10.1001/jama.297.15.joc70035).
Abstract 1541: Atypical Atrioventricular Nodal Reentrant Tachycardia with Anterior Retrograde Slow Pathway: Incidence, Electrophysiological Characteristics and Effect of Slow Pathway Ablation
Authors: Kiyoshi Otomo, Yasutoshi Nagata, Hiroshi Taniguchi, Kikuya Uno, Yoshito Iesaka
Journal: Circulation (2007)

BACKGROUND: Atypical AV nodal reentrant tachycardias (AVNRT) usually exhibit earliest retrograde atrial activation (ERAA) at the right posteroseptum (Rt-PS) or proximal coronary sinus (PCS). However, previous studies have shown that atypical AVNRT could rarely exhibit ERAA at the right anteroseptum (Rt-AS). The purpose of this study was to elucidate the incidence, characteristics and effect of slow pathway (SP) ablation in atypical AVNRT with an anterior retrograde SP. METHODS: The electrophysiological and ablation data were reviewed in 360 AVNRTs induced in 340 consecutive patients. Atypical AVNRT was differentiated from typical form by a longer H-A interval during ventricular pacing at the tachycardia cycle length (TCL) (HAp: =/&gt;70ms), and evidences for a lower common pathway (LCP), including second-degree AV block without tachycardia interruption, HAp longer than the HA interval during tachycardia (HAt). Atypical AVNRTs were classified into two types; the posterior type with ERAA at the Rt-PS or PCS; and anterior type with ERAA at the Rt-AS. RESULTS: In a total of 360 AVNRTs, there were 300 typical (83%) and 60 atypical forms (17%). Among the 60 atypical forms, 51 (14%) were classified into the posterior type, while the remaining 9 (3%) were classified into the anterior type. The anterior type of atypical AVNRT (TCL: 322+/−37ms) exhibited ERAA at the Rt-AS during the tachycardia and ventricular pacing, shorter A-H interval (162+/−39ms), longer HAt (167+/−40 ms), longer HAp (184+/−53ms), and evidences for a LCP, including a second-degree AV block during the tachycardia (n=4) and HAt being shorter than the H-Ap (n=9). All posterior types of atypical AVNRT were rendered non-inducible after an ablation to the ERAA site. In anterior type, the conventional SP ablation at the Rt-PS did not eliminate any of the 9 tachycardias; however, ablations at the right midseptum eliminated 7 (78%) of the 9 anterior types of atypical AVNRT. CONCLUSION: Atypical AVNRT with an anterior retrograde SP was observed in 3% of all AVNRTs. Conventional Rt-PS ablation was ineffective; and the midseptal ablation was modestly effective in this entity. The tachycardia circuit of the anterior type might be deviated to more anterior part of the Koch’s triangle than that of the posterior type.
All relevant costs and consequences should be measured
Authors: R. Hardie
Journal: BMJ (1995)

EDITOR,—On the basis of a comprehensive economic evaluation R H Behrens and J A Roberts conclude that “a national policy of immunising all travellers against typhoid and hepatitis A does not seem to be cost beneficial to the community.”1 While in principle such evaluations should help guide public health policy, considerable uncertainty surrounds many of the estimates used, and their conclusion should not compromise public health advice on the need for vaccination for certain categories of travellers.

Certain costs …
Mitoxantrone induces DNA topoisomerase II cleavage at translocation breakpoint hotspot in PML gene in acute promyelocytic leukemia
Authors: Anita Mistry, C A Felix, R Whitmarsh, Annabel Mason, A Reiter, B Cassinat, A Parry, C Walz, L Ades, I A Blair, N Osheroff, T J Littlewood, M Lafage-Pochitaloff, N C P Cross, C Chomienne, Ellen Solomon, P Fenaux, David Grimwade
Journal: Blood (2003)
Management of Lassa Fever in European countries
Authors: N Crowcroft
Journal: Eurosurveillance (2002)

The UK Public Health Laboratory Service hosted a meeting in London during November 2000 to discuss the management of Lassa fever following the four cases which had occurred in 1999/2000. Participants were invited because they had recent clinical or laboratory experience of managing cases of Lassa fever or had been involved in public health aspects of a case of this infection. The meeting was closed to enable free and frank discussion of confidential matters. This is a report of the general issues and recommendations which arose from the discussion.
Abstract 15929: Outcomes with Ticagrelor Versus Clopidogrel in Relation to High Sensitivity Troponin-T in Non-ST-Elevation Acute Coronary Syndrome Patients Managed with Early Invasive or Non-Invasive Treatment - A Substudy from the Prospective Randomized PLATelet Inhibition and Patient Outcomes (PLATO) Trial
Authors: Lars Wallentin, Stefan K James, Evangelos Giannitsis, Hugo A Katus, Richard C Becker, Christopher P Cannon, Jay Horrow, Steen Husted, Agneta Siegbahn, Gabriel P Steg, Robert F Storey, Lisa Wernroth, Robert A Harrington
Journal: Circulation (2012)
Dichotic listening during auditory hallucinations in patients with schizophrenia
Authors: M F Green, K Hugdahl, S Mitchell
Journal: American Journal of Psychiatry (1994)

Auditory hallucinations are a serious problem for a large subgroup of psychotic patients who do not respond optimally to neuroleptic medication. It has been hypothesized that hearing imaginary voices involves the same physiological processes as those involved in hearing real voices, but this hypothesis has not been conclusively confirmed.In this study a consonant-vowel version of the Dichotic Listening Test was used to assess the functional integration of the left hemisphere in hallucinating and nonhallucinating psychotic patients. The test was administered under three conditions: a nonforced attention condition, a condition in which attention was forced to the left ear, and one in which attention was forced to the right ear.The nonhallucinating patients showed the normal right ear advantage, which indicates a left hemisphere superiority in the processing of linguistic stimuli. In contrast, the hallucinating patients showed no ear advantage. Neither group was able to modify its performance when instructed to attend to either the left or the right ear. A subgroup of patients was tested in both hallucinating and nonhallucinating states, but the ear asymmetry was not noticeably different between these states.The results suggest that auditory hallucinations are associated with abnormalities in left hemisphere functioning and that these abnormalities might not be limited to the time of the auditory hallucinations. It is hypothesized that a relatively enduring left hemisphere abnormality may leave some patients at risk for auditory hallucinations.
Imatinib may enable complete resection in previously unresectable or metastatic GIST
Authors: S. Bauer, J. T. Hartmann, H. Lang, G. Antoch, O. Dirsch, P. Ebeling, M. De Wit, S. Seeber, M. Flasshove, J. Schütte
Journal: Journal of Clinical Oncology (2004)

9023 Background: Imatinib (I) induces remissions in the majority of pts with GIST (>70%) with yet uncertain median duration. Long-term survival has been reported in the pre-imatinib era only for pts who underwent complete resection. Very few data exist about resection of residual disease in previously unresectable patients responding to I. Methods: Between 10/2001 and 6/2003 51 pts with metastatic or unresectable GIST were treated (or registered for treatment) with I at the medical oncology units of the Universities of Essen and Tübingen, Germany. A prospective database was established to evaluate a neoadjuvant treatment for these patients. Resection was performed after maximum radiologic response to I. A total of 11 pts were registered (3/11 presented at ASCO 2003: #3288). Pt characteristics: median age: 62y (33–75); median of 2 laparotomies in the past (prev. metastasectomies in 5 pts); localization of metastases: liver (8), peritoneum (5) and retroperitoneum (1); median diameter of largest metastasis: 4.1cm (3–16.4); I dose: 400mg (-600) qd; median treatment duration: 56 wks (27–90); median no. of metastases before I: 8 (2–12); after I: 2 (0–12); Complete loss of PET activity was observed in 6/8 pts with glucose uptake in their tumors. Results: 11/51 pts (22%) in this analysis were allocated for surgery. Surgical procedures consisted of hepatic metastasectomy (6/11), resection of peritoneal (5/11) and retroperitoneal lesions (1/11). R0-resection was achieved in 10/11 pts. Postoperative complications occurred in 3/11 pts requiring prolonged hospitalization. Histopathological analysis revealed residual tumor cells in 10/11 pts, one pCR was observed. Following surgery, 9/11 pts received further I. One relapse occurred 26 wks after surgery. 10/11 pts remain in first NED status with a median FU of 27.4+ wks (4.4+ - 84.4+). All pts are alive with a median overall survival of 45.9+ mo (4+ - 85+). Conclusion: I induced resectability in 19% of metastatic GIST in our series. Since vital tumor cells were found in most tumors even after excellent treatment response early resection should be considered. The impact of resection on survival and course of disease remains as yet unclear. No significant financial relationships to disclose.
Abstract 15687: Loss of Tribbles 3 (TRIB3) Attenuates Pressure-Overload Induced Myocardial Hypertrophy
Authors: Eltyeb Abdelwahid, Rongxue Wu, Amy K Rines, Hossein Ardehali
Journal: Circulation (2014)

Introduction: Tribbles 3 (TRIB3) is a pseudokinase that regulates several biological functions such as cell proliferation and differentiation through its role in cellular metabolism. TRIB3 expression is modulated by various signals such as endoplasmic reticulum (ER) stress, nutrient availability, and insulin. The exact function of TRIB3 in the heart is largely unknown. We hypothesized that loss of TRIB3 protects against cardiac hypertrophy through its role in the regulation of cellular metabolism. Results: To elucidate the role of TRIB3 loss in the heart, we generated TRIB3 knock-out (KO) mice. The animals were then subjected to transverse aortic constriction (TAC) and sham-surgery control. In the sham operation groups, there was no hypertrophy in both TRIB3-/- and Wild type (WT) age matched control mice. WT mice subjected to TAC (WT-TAC) showed cardiac hypertrophy evidenced by increased heart weight/body weight, increased left ventricular wall thickness and increased cardiomyocyte cross-sectional area. These hypertrophic findings were significantly reduced in TRIB3 KO-TAC hearts (P&lt;0.05). Echocardiographic analysis revealed increased diastolic interventricular septum wall (IVSd), increased left ventricular wall posterior wall thickness (LVPWd) and decreased fractional shortening (FS) in WT-TAC mice, however these changes were significantly blocked in TRIB3 KO-TAC group suggesting that TAC-induced left ventricular hypertrophy and dysfunction was attenuated in TRIB3 KO mice (P&lt;0.05). The blunted response to hypertrophy seen in TRIB3 KO-TAC group was further demonstrated by the significant decrease in mRNA expression of myocardial hypertrophic markers (ANP, BNP and MHC) in TRIB3 KO-TAC hypertrophied left ventricles compared to WT-TAC control subjects (P&lt;0.05). Furthermore, our data indicated increased TRIB3 expression in the WT-TAC hypertrophied left ventricles compared to WT-Sham group (P&lt;0.05). Conclusions: The present study demonstrated that TRIB3 expression is promoted in hypertrophied hearts. TRIB3 deletion suppresses cardiac pressure overload-induced hypertrophy. Thus, TRIB3 is a novel target that plays a role in cardiac hypertrophy and maladaptation following pressure overload.
Multimedia: Sexually Transmitted Infections and AIDS in the Tropics
Authors: Gerard van Doornum
Journal: BMJ (1999)

Eds O P Arya, C A Hart


CABI Publishing, £60, pp 448 




ISBN 0 85199 262 5

———————

Rating: ★★★

A historical background to the subjects of sexually transmitted diseases and the tropics has been provided by D M Peers in a description of the campaigns to combat these diseases in colonial India during 1805-60: venereal diseases and the British army of the 19th century were, for many contemporaries, almost synonymous. About 150 years later, the picture of the world and the tropics has changed dramatically, and, as a consequence, so has that of tropical transmitted diseases.

Sexually Transmitted Infections and AIDS in the Tropics makes clear the profound impact that the AIDS epidemic and sexually transmitted diseases have had on societies in developing countries in recent decades, and the experienced contributors deal competently with the rapidly changing epidemiology of HIV infections. The short chapter on laboratory aspects reveals the urgent need for cheap, rapid, and reliable assays—the lack of resources too often precludes the use of sensitive and specific tests—but the book is not meant as a practical guide for laboratory management. The chapters on clinical aspects provide a good and concise description of the classic sexually transmitted infections and of those specific to the tropics—such as lymphogranuloma venereum and granuloma inguinale. Besides these subjects, relevant information is given on viral infections.

Special attention is paid to the problem oriented approach to infections when an aetiological diagnosis is not possible. The drawbacks and limitations of this approach are not overlooked, and it is well stated that information on the prevalence of specific diseases is required for the application of the approach. The book clearly and concisely describes the presenting problems associated with various sexually transmitted infections. On this basis case management can be based on flow charts and standardised treatment protocols.

The chapter describing the objectives of disease control have been written for healthcare professionals working in various settings. The arguments are repeated for a combination of controlling classic sexually transmitted infections and preventing and controlling AIDS.

The editors have chosen to avoid an extensive bibliography, and, regretfully, some of the chapters lack even a short list of recommended further reading. This book deserves to be used by many professionals, and I hope that it will be updated regularly in this rapidly changing world.
Abstract 4882: Inhibitor Kappa B Kinase Regulates Endothelial Nitric Oxide Synthase Activity and Nitric Oxide Generation
Authors: Sumathy Mohan, Natarajan Mohan, Linda Roman, Saima Humayun, Ryszard Konopinski
Journal: Circulation (2009)

The involvement of heat shock protein 90 (Hsp-90) in the regulation of eNOS activity is known. We recently demonstrated the increased interaction of Hsp-90 with IKK β in vascular endothelial cells under conditions of high glucose. However, whether this binding of IKK β to Hsp-90 will interfere with the binding of Hsp-90 to eNOS is not clear and the region on Hsp-90 to which IKK β binds is unknown. In this study, we examined whether the interaction of Hsp-90 with eNOS is compromised by competitive binding of IKK β . Our attempts to demonstrate competition between eNOS and IKK β for Hsp-90 using purified proteins confirmed that elevated levels of IKK β can dissociate eNOS-Hsp-90 complex. Hsp-90 and eNOS with increasing concentrations of purified Gst-IKK β were incubated for 2h at 4°C. Immunoprecipitation of this complex with anti-eNOS antibody followed by Immunoblotting using anti-Hsp-90 antibody demonstrated reduced amounts of Hsp-90 associated to eNOS as concentration of IKK β increases (Fig 1A ). The supernatants were re-precipitated with anti-GST antibody and the immune complex was analyzed for the presence of Hsp-90. Immunoblot showed the presence of Hsp-90 with higher concentration of IKK β (1B). Further, we investigated whether IKK β can inhibit eNOS enzyme activity by dissociating Hsp-90-eNOS complex. Nitric oxide formation was measured at 23°C using the hemoglobin capture assay. Addition of IKK β significantly blocked eNOS activity (Fig 2 ). Also, In vitro kinase assay performed using bovine aortic endothelial cell lysates and purified proteins demonstrated possible phosphorylation of Hsp-90 by IKK β kinase. These results show the significance of IKK β in regulating eNOS activity. Figure 1 Figure 2
Abstract 2386: Asymptomatic Left Ventricular Systolic Dysfunction as a Predictor of Incident Heart Failure and Mortality in the Elderly: The Cardiovascular Health Study
Authors: Jay Pandhi, Willem J Kop, John S Gottdiener
Journal: Circulation (2008)

Left ventricular systolic dysfunction (LVSD) is an important predictor of outcomes in heart failure (HF) patients. Adverse effects of LVSD in individuals without heart failure, also known as asymptomatic LVSD (ALVSD), are not well established in the elderly. This study reports outcomes and evaluates the impact of LVSD in elderly subjects with ALVSD. The Cardiovascular Health Study is a multicenter longitudinal cohort study designed to assess cardiac risk factors and outcomes in a community-based population 65 years and older. The incidence of HF and mortality was evaluated in those with ALVSD with a median follow-up of 11.9 years. Cox regression was used, adjusting for demographics and cardiac risk factors, and stratified by severity of LVSD. Incident HF occurred in 39.2% of those with ALVSD vs. 22.8% in those without LVSD (RR = 1.51, CI = 1.25–1.84). Impaired ejection fraction (EF) (&lt; 45%) was associated with more than twice the risk of incident HF than normal systolic function (RR = 2.21; CI 1.67–2.91). Individuals with borderline EF (45–55%) did not have an increased risk of incident HF (RR = 1.21; CI 0.94–1.56). The severity of LVSD was also predictive of mortality: borderline LVSD RR = 1.23 (CI 1.04–1.47) for all-cause mortality and 1.60 (CI 1.26–2.03) for cardiac death; impaired LVSD RR = 1.54 (CI 1.24–1.92) for all-cause mortality and RR = 2.12 (CI 1.60–2.81) for cardiac death. ALVSD is associated with increased risk of heart failure, death, and cardiac death when compared to normal systolic function. Furthermore, the degree of systolic dysfunction has a significant impact in predicting these outcomes in elderly individuals with ALVSD.
A phase II study of capecitabine plus oxaliplatin and radiation therpy, XELOX-XRT, in squamous cell carcinoma (SCCA) of the anal canal: A preliminary analysis
Authors: C. Eng, C. H. Crane, G. L. Rosner, M. A. Rodriguez-Bigas, J. M. Skibber, K. R. Bogaard, M. E. Delclos, Y. M. Lassere, P. M. Hoff, J. L. Abbruzzese
Journal: Journal of Clinical Oncology (2005)

4271 Background: The limitations of chemoradiation for SCCA of the anal canal include significant acute toxicity and high rates of relapse in locally advanced disease. The aim of this study is to assess the rate of treatment-related toxicities, time to treatment failure, and response rate in patients with locally advanced SCCA (AJCC stage II-IIIB) of the anal canal treated with XELOX-XRT. Methods: Patients received capecitabine (825 mg/m2 orally BID, M-F), weekly oxaliplatin (50 mg/m2, intravenously), and radiation therapy (45 Gy for T1, 55 Gy for T2, or 59 Gy for T3–4 lesions). Chemotherapy is delivered on the days of radiation therapy only, M-F, weeks 1–6. The estimated accrual rate is 2–3 patients per month for a total of 60 patients. Interim safety monitoring is to be completed after every 10 patients. A multidisciplinary team is involved during all aspects of the patient’s treatment. Results: Patient accrual was initiated in June 2004. Thus far, 3 patients have enrolled and completed therapy. Two patients are currently evaluable for response; both patients have had a clinical complete response. Predominant grade 3 toxicities encountered include diarrhea, radiation dermatitis, pain, and dehydration. No incidences of Grade 4 toxicity were noted. Conclusions: Patient accrual is ongoing. Updated preliminary toxicities and response will be reported. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi
Cruise-Ship–Associated Legionnaires Disease, November 2003–May 2004
Authors: C. Joseph, J. van Wijngaarden, P. Mshar, C. Oravetz, A. M. Fix, C. A. Genese, G. S. Johnson, M. Kacica, B. Weant, P. Jenkins, N. Baker, D. Forney, J. Ames, G. Vaughan, J. Schnoor, D. Kim, M. Guerra, B. Fields, M. Moore, C. Newbern, M. Thigpen
Journal: JAMA (2005)

Texas, Utah, Virginia, West Virginia, Wisconsin, and Wyoming.‡In addition to AIDS cases, in June 2000, New York began requiring that all confirmed HIV diagnostic tests, detectable HIV viral load tests, and CD4 counts of Ͻ500 µL be reported to the health department.Healthcare providers are required to report all cases of HIV diagnosis, HIV illness, and AIDS.In June 2005, reporting requirements were changed to include all HIV viral load tests and all CD4 counts, regardless of value.§Alabama, Alaska, Arizona, Arkansas,