tbuckley/cabot-search huggingface dataset:
Prevalence of Antimicrobial Use in US Acute Care Hospitals, May-September 2011
Authors: Shelley S. Magill, Jonathan R. Edwards, Zintars G. Beldavs, Ghinwa Dumyati, Sarah J. Janelle, Marion A. Kainer, Ruth Lynfield, Joelle Nadle, Melinda M. Neuhauser, Susan M. Ray, Katherine Richards, Richard Rodriguez, Deborah L. Thompson, Scott K. Fridkin
Journal: JAMA (2014)

Inappropriate antimicrobial drug use is associated with adverse events in hospitalized patients and contributes to the emergence and spread of resistant pathogens. Targeting effective interventions to improve antimicrobial use in the acute care setting requires understanding hospital prescribing practices.
Processing of Switch Transcripts Is Required for Targeting of Antibody Class Switch Recombination
Authors: Katharina Hein, Matthias G.O. Lorenz, Gregor Siebenkotten, Katja Petry, Rainer Christine, Andreas Radbruch
Journal: The Journal of Experimental Medicine (1998)

Antibody class switching is mediated by somatic recombination between switch regions of the immunoglobulin heavy chain gene locus. Targeting of recombination to particular switch regions is strictly regulated by cytokines through the induction of switch transcripts starting 5' of the repetitive switch regions. However, switch transcription as such is not sufficient to target switch recombination. This has been shown in mutant mice, in which the I-exon and its promoter upstream of the switch region were replaced with heterologous promoters. Here we show that, in the murine germline targeted replacement of the endogenous gamma1 promoter, I-exon, and I-exon splice donor site by heterologous promoter and splice donor sites directs switch recombination in activated B lymphocytes constitutively to the gamma1 switch region. In contrast, switch recombination to IgG1 is inhibited in mutant mice, in which the replacement does not include the heterologous splice donor site. Our data unequivocally demonstrate that targeting of switch recombination to IgG1 in vivo requires processing of the Igamma1 switch transcripts. Either the processing machinery or the processed transcripts are involved in class switch recombination.
Very Long-Term Survival and Durability of Mitral Valve Repair for Mitral Valve Prolapse
Authors: Dania Mohty, Thomas A. Orszulak, Hartzell V. Schaff, Jean-Francois Avierinos, Jamil A. Tajik, Maurice Enriquez-Sarano
Journal: Circulation (2001)

Mitral regurgitation (MR) due to mitral valve prolapse (MVP) is often treatable by surgical repair. However, the very long-term (>10-year) durability of repair in both anterior leaflet prolapse (AL-MVP) and posterior leaflet prolapse (PL-MVP) is unknown.In 917 patients (aged 65+/-13 years, 68% male), surgical correction of severe isolated MR due to MVP (679 repairs and 238 replacements [MVRs]) was performed between 1980 and 1995. Survival after repair was better than survival after MVR for both PL-MVP (at 15 years, 41+/-5% versus 31+/-6%, respectively; P=0.0003) and AL-MVP (at 14 years, 42+/-8% versus 31+/-5%, respectively; P=0.003). In multivariate analysis adjusting for predictors of survival, repair was independently associated with lower mortality in PL-MVP (adjusted risk ratio [RR] 0.61, 95% CI 0.44 to 0.85; P=0.0034) and in AL-MVP (adjusted RR 0.67, 95% CI 0.47 to 0.96; P=0.028). The reoperation rate was not different after repair or MVR overall (at 19 years, 20+/-5% for repair versus 23+/-5% for MVR; P=0.4) or separately in PL-MVP (P=0.3) or AL-MVP (P=0.3). However, the reoperation rate was higher after repair of AL-MVP than after repair of PL-MVP (at 15 years, 28+/-7% versus 11+/-3%, respectively; P=0.0006). From the 1980s to the 1990s, the RR of reoperation after repair of AL-MVP versus PL-MVP did not change (RR 2.5 versus 2.7, respectively; P=0.58), but the absolute rate of reoperation decreased similarly in PL-MVP and AL-MVP (at 10 years, from 10+/-3% to 5+/-2% and from 24+/-6% to 10+/-2%, respectively; P=0.04).In severe MR due to MVP, mitral valve repair compared with MVR provides improved very long-term survival after surgery for both AL-MVP and PL-MVP. Reoperation is similarly required after repair or replacement but is more frequent after repair of AL-MVP. Recent improvement in long-term durability of repair suggests that it should be the preferred mode of surgical correction of MVP whether it affects anterior or posterior leaflets and is an additional incentive for early surgery of severe MR due to MVP.
Effect of Daily Vitamin E and Multivitamin-Mineral Supplementation on Acute Respiratory Tract Infections in Elderly Persons
Authors: Judith M. Graat, Evert G. Schouten, Frans J. Kok
Journal: JAMA (2002)

ContextImmune response in elderly individuals has been reported to improve after micronutrient supplementation. However, efficacy trials evaluating infectious diseases as outcomes are scarce and inconclusive.ObjectiveTo investigate the effect of daily multivitamin-mineral and vitamin E supplementation on incidence and severity of acute respiratory tract infections in elderly individuals.DesignA randomized, double blind, placebo-controlled, 2 × 2 factorial trial.Setting and ParticipantsA total of 652 noninstitutionalized individuals aged 60 years or older enrolled from 2 community-based sampling strategies in the Wageningen area of the Netherlands, conducted from 1998 to 2000. At baseline, 6% of participants had suboptimal ascorbic acid and 1.3% had suboptimal α-tocopherol plasma concentration.InterventionPhysiological doses of multivitamin-minerals, 200 mg of vitamin E, both, or placebo.Main Outcome MeasuresIncidence and severity of self-reported acute respiratory tract infections at 15 months, as assessed by a nurse (telephone contact), home visits, and microbiological and serological testing in subsets of patients.ResultsDuring a median observation period of 441 days, 443 (68%) of 652 participants recorded 1024 respiratory tract infection episodes. The incidence rate ratio of acute respiratory tract infection for multivitamin-mineral supplementation was 0.95 (95% confidence interval, 0.75-1.15; P = .58) and for vitamin E supplementation, 1.12 (95% confidence interval, 0.88-1.25; P = .21). Severity of infections was not influenced by multivitamin-mineral supplementation. For vitamin E vs no vitamin E, severity was worse: median (interquartile range) for illness-duration was 19 (9-37) vs 14 (6-29) days, P = .02; number of symptoms, 6 (3-8) vs 4 (3-8), P = .03; presence of fever, 36.7% vs 25.2%, P = .009; and restriction of activity, 52.3% vs 41.1%, P = .02.ConclusionsNeither daily multivitamin-mineral supplementation at physiological dose nor 200 mg of vitamin E showed a favorable effect on incidence and severity of acute respiratory tract infections in well-nourished noninstitutionalized elderly individuals. Instead we observed adverse effects of vitamin E on illness severity.
Evaluation of the force-frequency relationship as a descriptor of the inotropic state of canine left ventricular myocardium.
Authors: P A Anderson, J S Rankin, C E Arentzen, R W Anderson, E A Johnson
Journal: Circulation Research (1976)

The short-term force-frequency characteristics of canine left ventricular myocardium were examined in both isolated and intact preparations by briefly pertubing the frequency of contraction with early extrasystoles. The maximum rate of rise of isometric tension (Fmas) of the isolated trabeculae carneae was potentiated by the introduction of extrasystoles. The ratio of Fmas of potentiated to control beats (force-frequency ratio) was not altered significantly by a change in muscle length. However, exposure of the trabeculae to isoproterenol (10(-7)M) significantly changed the force-frequency ratio obtained in response to a constant frequency perturbation. Similar experiments were performed on chronically instrumented conscious dogs. Left ventricular minor axis diameter was measured with implanted pulse-transit ultrasonic dimension transducers, and intracavitary pressure was measured with a high fidelity micromanometer. Atrial pacing was performed so that the end-diastolic diameters of the beats preceding and following the extrasystole could be made identical. Large increases in the maximum rate of rise of pressure (Pmas) were seen in the contraction after the extrasystole. The ratio of Pmax of the potentiated beat to that of the control beat was not changed by a 9% increase in the end-diastolic diameter, produced by saline infusion. Conversely, isoproterenol significantly altered this relationship in the same manner as in the isolated muscle. Thus, either in vitro or in situ, left ventricular myocardium exhibits large functional changes in response to brief perturbations in rate. The isoproterenol and length data indicate that the force-frequency ratio reflects frequency-dependent changes in the inotropic state, independent of changes in length.
Hematin Treatment of Acute Porphyria
Authors: Andrew Peterson
Journal: JAMA (1976)

Intravenous infusions of hematin in a young woman with acute porphyria in profound relapse was followed within 48 hours by remission of symptoms and rapid recovery. From a state of severe central and peripheral nervous-system involvement, the patient recovered so completely that she was able to leave the hospital in less than a month, with only a residual weakness of her arms. Serial studies of serum and urinary levels of porphyrin precursors and serum level of hematin provided highly important information about the effect of hematin on acute porphyria. (<i>JAMA</i>235:520-522, 1976)
Quantification of Circulating Endothelial Cells by Flow Cytometry
Authors: Michiel H. Strijbos, Jaco Kraan, Cor H.J. Lamers, Stefan Sleijfer, Jan W. Gratama
Journal: Clinical Cancer Research (2009)

To the Editors: We read with great interest the article by Mancuso et al. ([1][1]) in the January edition of Clinical Cancer Research . In this article, the authors describe the validation of a novel multicolor flow cytometrical assay that allows the quantification of both circulating endothelial
Association of the MIC-A gene and HLA-B51 with Behcet's disease in Arabs and non-Ashkenazi Jews in Israel
Authors: R Cohen
Journal: Annals of the Rheumatic Diseases (2002)

Behçet's disease is known to be strongly associated with HLA-B51 in many different ethnic groups. Recently, it was suggested that MIC-A (major histocompatibility complex class I related gene A) is the pathogenic gene after strong association was found between the MIC-A A6 allele of the transmembrane region and the disease in Japanese and Greek patients, although in Greek patients this association was found to be due to linkage disequilibrium with HLA-B51.To investigate microsatellite polymorphism in Arab and non-Ashkenazi Jewish (NAJ) patients in Israel, to determine whether this association occurs in these groups with Behçet's disease, and elucidate the associated HLA allele of the disease.Forty four Israeli patients with Behçet's disease, including 20 Arabs and 24 NAJ, and 130 ethnically matched healthy controls were examined for MIC-A microsatellite polymorphism of the transmembrane region using polymerase chain reaction, autoradiography, and sequence analysis.The MIC-A A6 allele was significantly more frequent in the Arab patient group (19/20 (95%)) than in healthy Arab controls (25/42 (60%)) (p(corr)=0.015, OR=12.92), but not in the NAJ patients (16/24 (67%)) compared with NAJ healthy controls (48 /88 (55%)) (p(corr)=1.02, OR=1.667). In stratification analysis of the Arab subgroup, on the confounding effect of MIC-A A6 on HLA-B51 association and vice versa, Behçet's disease was distinctly associated only with HLA-B51.These results imply strong association between the MIC-A A6 allele and the disease in Israeli Arabs, but not in Israeli NAJ patients. The stratification analysis indicates that this association results secondarily from a strong linkage disequilibrium with HLA-B51, and the real disease susceptibility gene which plays a part in the development of Behçet's disease is most probably the HLA-B51 allele itself.
Increased faecal serine protease activity in diarrhoeic IBS patients: a colonic lumenal factor impairing colonic permeability and sensitivity
Authors: K. Gecse, R. Roka, L. Ferrier, M. Leveque, H. Eutamene, C. Cartier, A. Ait-Belgnaoui, A. Rosztoczy, F. Izbeki, J. Fioramonti, T. Wittmann, L. Bueno
Journal: Gut (2008)

<h3>Objectives:</h3> Diarrhoea-predominant irritable bowel syndrome (IBS-D) is characterised by elevated colonic lumenal serine protease activity. The aims of this study were (1) to investigate the origin of this elevated serine protease activity, (2) to evaluate if it may be sufficient to trigger alterations in colonic paracellular permeability (CPP) and sensitivity, and (3) to examine the role of the proteinase-activated receptor-2 (PAR-2) activation and signalling cascade in this process. <h3>Patients and methods:</h3> Faecal enzymatic activities were assayed in healthy subjects and patients with IBS, ulcerative colitis and acute infectious diarrhoea. Following mucosal exposure to supernatants from control subjects and IBS-D patients, electromyographic response to colorectal balloon distension was recorded in wild-type and PAR-2<sup>–/–</sup> mice, and CPP was evaluated on colonic strips in Ussing chambers. Zonula occludens-1 (ZO-1) and phosphorylated myosin light chain were detected by immunohistochemistry. <h3>Results:</h3> The threefold increase in faecal serine protease activity seen in IBS-D patients compared with constipation-predominant IBS (IBS-C) or infectious diarrhoea is of neither epithelial nor inflammatory cell origin, nor is it coupled with antiprotease activity of endogenous origin. Mucosal application of faecal supernatants from IBS-D patients in mice evoked allodynia and increased CPP by 92%, both of which effects were prevented by serine protease inhibitors and dependent on PAR-2 expression. In mice, colonic exposure to supernatants from IBS-D patients resulted in a rapid increase in the phosphorylation of myosin light chain and delayed redistribution of ZO-1 in colonocytes. <h3>Conclusions:</h3> Elevated colonic lumenal serine protease activity of IBS-D patients evokes a PAR-2-mediated colonic epithelial barrier dysfunction and subsequent allodynia in mice, suggesting a novel organic background in the pathogenesis of IBS.
End-of-treatment but not interim PET scan predicts outcome in nonbulky limited-stage Hodgkin’s lymphoma
Authors: J.A. Barnes, A.S. LaCasce, K. Zukotynski, D. Israel, Y. Feng, D. Neuberg, C.E. Toomey, E.P. Hochberg, G.P. Canellos, J.S. Abramson
Journal: Annals of Oncology (2010)
Doxorubicin clearance in the obese.
Authors: K A Rodvold, D A Rushing, D A Tewksbury
Journal: Journal of Clinical Oncology (1988)

A study was carried out to examine the effect, if any, of obesity on doxorubicin pharmacokinetics. Body weight was found to be significantly related to doxorubicin clearance (r = -.75; P less than .001) and elimination half-life (r = .62; P = .003). Thus, the contribution of obesity on pharmacokinetics of antineoplastic agents should be taken into consideration in the analysis of clinical data with respect to toxicity and tumor response. Twenty-one patients were studied with their first course of doxorubicin (50 to 70 mg/m2) administered as a 60-minute intravenous (IV) infusion. Patients were divided into three groups on the basis of percentage of ideal body weight (IBW): normal (less than 115% IBW), mildly obese (115% to 130% IBW), and obese (greater than 130% IBW). Blood samples were collected up to 48 hours after the infusion and analyzed for doxorubicin and its metabolite, doxorubicinol, by high performance liquid chromatography. Doxorubicin area under the curve (AUC) was greater in obese than in normal patients (2,209 v 1,190 ng h/mL; P less than .05), yielding correspondingly reduced systemic clearance of the agent in obese patients (891 v 1,569 mL/min; P less than .001). The mean elimination half-life (T1/2) was 20.4 hours in the obese patients and 13.0 hours in the normal patients. The apparent volume of distribution (Vss) was not significantly different among the three groups of patients, indicating that the prolonged T1/2 in the obese patients is due to the reduction in clearance. The AUC and T1/2 of doxorubicinol were similar among all patient groups.
The Role of the Mammalian Target Of Rapamycin (mTOR) in Renal Disease
Authors: Wilfred Lieberthal, Jerrold S. Levine
Journal: Journal of the American Society of Nephrology (2009)

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays a pivotal role in mediating cell size and mass, proliferation, and survival. mTOR has also emerged as an important modulator of several forms of renal disease. mTOR is activated after acute kidney injury and contributes to renal regeneration and repair. Inhibition of mTOR with rapamycin delays recovery of renal function after acute kidney injury. Activation of mTOR within the kidney also occurs in animal models of diabetic nephropathy and other causes of progressive kidney disease. Rapamycin ameliorates several key mechanisms believed to mediate changes associated with the progressive loss of GFR in chronic kidney disease. These include glomerular hypertrophy, intrarenal inflammation, and interstitial fibrosis. mTOR also plays an important role in mediating cyst formation and enlargement in autosomal dominant polycystic kidney disease. Inhibition of mTOR by rapamycin or one of its analogues represents a potentially novel treatment for autosomal dominant polycystic kidney disease. Finally, inhibitors of mTOR improve survival in patients with metastatic renal cell carcinoma.
Pharmacotherapy for Heart Failure in Patients with Renal Insufficiency
Authors: Michael G. Shlipak
Journal: Annals of Internal Medicine (2003)

Clinical trials have demonstrated that angiotensin-converting enzyme (ACE) inhibitors, -blockers, and spironolactone improve survival in patients with heart failure. Because patients with heart failure and renal insufficiency have been underrepresented in these trials, little evidence is available to guide clinicians in the optimal management of patients with both conditions. Approximately one third to one half of patients with heart failure have renal insufficiency (estimated glomerular filtration rate [GFR] <60 mL/min per 1.73 m2), and renal insufficiency is among the strongest predictors of mortality in patients with heart failure. Evidence supports the use of ACE inhibitors to improve survival in patients with moderate renal insufficiency (GFR, 30 to 60 mL/min per 1.73 m2), but there is little evidence with which to weigh the risks and benefits in patients with more advanced renal dysfunction. -Blockers improve survival in patients with heart failure, and their beneficial effect is unlikely to differ according to renal function. Spironolactone improves outcomes in patients with advanced heart failure, but renal insufficiency appears to increase risk for hyperkalemia and limits the use of the drug in patients with severe renal insufficiency. Future clinical trials in heart failure should include a representative number of patients with renal insufficiency to improve the evidence base and outcomes in this vulnerable population.
Association of Testosterone Therapy With Mortality, Myocardial Infarction, and Stroke in Men With Low Testosterone Levels
Authors: Rebecca Vigen, Colin I. O'Donnell, Anna E. Barón, Gary K. Grunwald, Thomas M. Maddox, Steven M. Bradley, Al Barqawi, Glenn Woning, Margaret E. Wierman, Mary E. Plomondon, John S. Rumsfeld, P. Michael Ho
Journal: JAMA (2013)

Rates of testosterone therapy are increasing and the effects of testosterone therapy on cardiovascular outcomes and mortality are unknown. A recent randomized clinical trial of testosterone therapy in men with a high prevalence of cardiovascular diseases was stopped prematurely due to adverse cardiovascular events raising concerns about testosterone therapy safety.To assess the association between testosterone therapy and all-cause mortality, myocardial infarction (MI), or stroke among male veterans and to determine whether this association is modified by underlying coronary artery disease.A retrospective national cohort study of men with low testosterone levels (<300 ng/dL) who underwent coronary angiography in the Veterans Affairs (VA) system between 2005 and 2011.Primary outcome was a composite of all-cause mortality, MI, and ischemic stroke.Of the 8709 men with a total testosterone level lower than 300 ng/dL, 1223 patients started testosterone therapy after a median of 531 days following coronary angiography. Of the 1710 outcome events, 748 men died, 443 had MIs, and 519 had strokes. Of 7486 patients not receiving testosterone therapy, 681 died, 420 had MIs, and 486 had strokes. Among 1223 patients receiving testosterone therapy, 67 died, 23 had MIs, and 33 had strokes. At 3 years after coronary angiography, the Kaplan-Meier estimated cumulative percentages with events were 19.9%in the no testosterone therapy group vs 25.7%in the testosterone therapy group,with an absolute risk difference of 5.8%(95%CI, -1.4%to 13.1%) [corrected].The Kaplan-Meier estimated cumulative percentages with events among the no testosterone therapy group vs testosterone therapy group at 1 year after coronary angiography were 10.1% vs 11.3%; at 2 years, 15.4% vs 18.5%; and at 3 years, 19.9% vs 25.7 [corrected].There was no significant difference in the effect size of testosterone therapy among those with and without coronary artery disease (test for interaction, P = .41).Among a cohort of men in the VA health care system who underwent coronary angiography and had a low serum testosterone level, the use of testosterone therapy was associated with increased risk of adverse outcomes. These findings may inform the discussion about the potential risks of testosterone therapy.
Cardioprotection by Ischemic Postconditioning Is Lost in Aged and STAT3-Deficient Mice
Authors: Kerstin Boengler, Astrid Buechert, Yvonne Heinen, Christin Roeskes, Denise Hilfiker-Kleiner, Gerd Heusch, Rainer Schulz
Journal: Circulation Research (2007)

The cardioprotection by ischemic preconditioning is lost in aged wild-type and in STAT3 (signal transducer and activator of transcription 3)-deficient mice. The aim of the present study was to analyze whether or not ischemic postconditioning (iPoco) was effective in aged mice hearts and whether iPoco was dependent on STAT3. Young (3 months) and aged (>13 months) C57Bl6/J mice underwent 30 minutes of ischemia and 2 hours of reperfusion without or with iPoco (3 cycles of 10 seconds of ischemia/10 seconds of reperfusion [3x10] or 5 cycles of 5 seconds of ischemia/5 seconds of reperfusion [5x5] at the beginning of reperfusion). In young mice, both iPoco3x10 and iPoco5x5 reduced infarct size (IS), whereas in aged mice, only iPoco5x5 was effective in reducing IS. In young mice, iPoco3x10 increased the phosphorylated over total STAT3 (phosphorylated STAT3/STAT3) ratio at 10 minutes of reperfusion in the postconditioned anterior wall compared with the control posterior wall. In aged mice hearts, total STAT3 and phosphorylated STAT3/STAT3 in the anterior wall at reperfusion were reduced compared with young mice hearts. In young mice hearts subjected to iPoco3x10 but pretreated with the JAK-2 inhibitor AG-490, phosphorylated STAT3/STAT3 was reduced in the anterior wall compared with untreated young mice hearts, and IS reduction by iPoco3x10 was abolished. Furthermore, in young mice with a cardiomyocyte-restricted deletion of STAT3, iPoco3x10 failed to reduce IS, whereas iPoco5x5 reduced IS. Thus, cardioprotection by iPoco is dependent on the postconditioning protocol in aged and STAT3-deficient hearts. The reduced levels of STAT3 with increasing age may contribute to the age-related loss of iPoco.