tbuckley/cabot-search huggingface dataset:
Meta-Analysis: Methods for Diagnosing Intravascular Device–Related Bloodstream Infection
Authors: Nasia Safdar, Jason P. Fine, Dennis G. Maki
Journal: Annals of Internal Medicine (2005)

Background: No consensus exists on the best methods for diagnosis of intravascular device (IVD)–related bloodstream infection. Purpose: To identify the most accurate methods for diagnosis of IVD-related bloodstream infection. Data Sources: 51 English-language studies published from 1966 to 31 July 2004. Study Selection: Studies of diagnostic tests for IVD-related bloodstream infection that described a reference standard and provided sufficient data to calculate sensitivity and specificity. Data Extraction: Study quality, diagnostic tests examined, patient characteristics, prevalence, sensitivity, and specificity. Data Synthesis: Pooled sensitivity and specificity were calculated for 8 diagnostic methods. Summary measures of accuracy were Q* (the upper leftmost point on the summary receiver-operating characteristic curve) and mean D (a log odds ratio). Subgroup analyses were used to assess heterogeneity. Overall, the most accurate test was paired quantitative blood culture (Q* = 0.94 [95% CI, 0.88 to 1.0]), followed by IVD-drawn qualitative blood culture (Q* = 0.89 [CI, 0.79 to 0.99]) and the acridine orange leukocyte cytospin test (Q* = 0.89 [CI, 0.79 to 0.91]). The most accurate catheter segment culture test was quantitative culture (Q* = 0.87 [CI, 0.81 to 0.93]), followed by semi-quantitative culture (Q* = 0.84 [CI, 0.80 to 0.88]). Significant heterogeneity in pooled sensitivity and specificity was observed across all test categories. Limitations: The limited number of studies of some of the diagnostic methods precludes precise estimates of accuracy. Conclusions: Paired quantitative blood culture is the most accurate test for diagnosis of IVD-related bloodstream infection. However, most other methods studied showed acceptable sensitivity and specificity (both >0.75) and negative predictive value (>99%). The positive predictive value of all tests increased greatly with high pretest clinical probability. Catheters should not be cultured routinely but rather only if IVD-related bloodstream infection is suspected clinically.
Empirical approaches for the investigation of toxicant-induced loss of tolerance.
Authors: C Miller, N Ashford, R Doty, M Lamielle, D Otto, A Rahill, L Wallace
Journal: Environmental Health Perspectives (1997)

It has been hypothesized that sensitivity to low-level chemical exposures develops in two steps: initiation by an acute or chronic chemical exposure, followed by triggering of symptoms by low levels of previously tolerated chemical inhalants, foods, or drugs. The Working Group on Toxicant-induced Loss of Tolerance has formulated a series of research questions to test this hypothesis: Do some individuals experience sensitivity to chemicals at levels of exposure unexplained by classical toxicological thresholds and dose-response relationships, and outside normally expected variation in the population? Do chemically sensitive subjects exhibit masking that may interfere with the reproducibility of their responses to chemical challenges? Does chemical sensitivity develop because of acute, intermittent, or continuous exposure to certain substances? If so, what substances are most likely to initiate this process? An experimental approach for testing directly the relationship between patients' reported symptoms and specific exposures was outlined in response to the first question, which was felt to be a key question. Double-blind, placebo-controlled challenges performed in an environmentally controlled hospital facility (environmental medical unit) coupled with rigorous documentation of both objective and subjective responses are necessary to answer this question and to help elucidate the nature and origins of chemical sensitivity.
HM-PAO SPECT AND GO-DTPA ENHANCED HR IMAGING IN CNS MANIFESTATION OF AIDS
Authors: Michel Cordas, H. Henkes, J. Hunger, R. Jochens, W. Heise, R. Felix
Journal: Clinical Nuclear Medicine (1989)

Cordas, Michel; Henkes, H.; Hunger, J.; Jochens, R.; Heise, W.; Felix, R. Author Information
Selective Venous Sampling for Gastrin to Localize Gastrinomas
Authors: JAY A. CHERNER
Journal: Annals of Internal Medicine (1986)

In 27 consecutive patients with Zollinger-Ellison syndrome, we prospectively evaluated the ability of selective venous sampling for gastrin to localize gastrinomas, then compared the results with those from imaging studies and with findings at surgery. All patients had a gastrin gradient, but in only 20 patients was it significant. Neither the magnitude of the gastrin gradient nor its presence or absence correlated with the frequency with which gastrinoma was found at surgery. A gastrinoma was found at surgery in 15 patients, of whom 12 had positive imaging studies, 11 had a significant gastrin gradient, 14 had both tests positive, and 1 had both tests negative. A gastrinoma was not found at surgery in 12 patients, of whom 8 had a significant gradient and none had a positive imaging study. Gastrin sampling has equal sensitivity with imaging studies in localizing gastrinoma, but imaging studies have higher positive and negative predictive values and higher specificity. Thus, selective venous sampling for gastrin is much less useful in localizing gastrinoma than has been suggested and should not be routinely done preoperatively in patients with Zollinger-Ellison syndrome.
Balancing benefits and harms in health care: Observational data on harm are already included in systematic reviews
Authors: T. Jefferson
Journal: BMJ (2003)

Editor—The correspondence on the issue of including observational data of harm in systematic reviews surprised us.1,2 The tone of the prose implied that this might happen in the future, and the limits of randomised controlled trials discussed told readers what anyone working in assessing adverse events knows only too well. Observational data have been included in systematic reviews of possible harms for some time, precisely for the reasons that Johnston illustrates for vaccinations.2
Protein Kinase A Does Not Alter Economy of Force Maintenance in Skinned Rat Cardiac Trabeculae
Authors: Pieter P. de Tombe, G.J.M. Stienen
Journal: Circulation Research (1995)

Abstract Recent mechanical, biochemical, and energetic experiments have suggested that catecholamines may increase the cycling rate of cross-bridges independent of changes in intracellular calcium. An increased rate of cross-bridge cycling is expected to result in decreased economy of force maintenance. The present study tested this hypothesis directly by measuring the rate of ATP consumption in skinned cardiac trabeculae as a function of steady state force. Rat cardiac trabeculae were skinned with Triton X-100. Resting sarcomere length was measured by laser diffraction, and ATP consumption was assessed by an enzyme-coupled optical technique. Force-[Ca 2+ ] relations were fit to a modified Hill equation. Force dependency of the rate of ATP consumption was analyzed by multiple linear regression analysis. β-Adrenergic stimulation was mimicked by incubation of the skinned muscle preparation with the catalytic subunit of protein kinase A (PKA). Treatment with PKA (3 μg/mL, 40 minutes) induced a significant (65±23%, P =.01) increase in [Ca 2+ ] required for half-maximal steady state force, whereas the steepness of the force-[Ca 2+ ] relation was not affected. The rate of ATP consumption was linearly correlated with steady state force, regardless of PKA treatment status ( P &lt;.001). However, neither the slope nor the intercept was affected by PKA treatment. Hence, PKA treatment did not affect either the maximum rate of ATP consumption or the economy of force maintenance. These results suggest that β-adrenergic stimulation does not alter the rate-limiting step of cross-bridge cycling during isometric contraction in myocardium.
Urokinase-type plasminogen activator in human eccrine sweat
Authors: T. TAKEMURA, T. HIBINO, K. SATO
Journal: British Journal of Dermatology (1993)

The presence of urokinase-type plasminogen activator (uPA) in human eccrine sweat has not been reported previously. Clean sweat was obtained from the upper trunk and arms of subjects which had been painted with white petrolatum to minimize epidermal contamination. Sweat was concentrated ×50 by ultrafiltratlon, and its PA activity determined by the two-step assay method (conversion of plasminogen to plasmin with the subsequent assay of plasmin activity using the substrate S-2251), PA activity was detectable in nine of 17 subjects by this method, which probably represents an underestimate of the true activity because of possible loss of the enzyme during concentration. Scraped (crude) sweat samples contained less PA activity. Sephacryl S-200 gel chromatography of the PA-positive pooled sweat showed a major peak of PA activity at Mr 55,OOO. Gelatin-polyacrylamide enzymography revealed a major PA band at Mr 55,000 and a minor band at 33,000. Sweat PA activity was 94% inhibited by epidermal PA inhibitor and anti-uPA IgG, but not by anti-tPA IgG. We conclude that the PA activity in sweat is derived from the sweat gland and is most likely of the urokinase type. The physiological significance of sweat uPA remains to be determined.
Alpha-V-beta-3• integrin-mediated adenoviral transfer of interleukin-12 at the periphery of hepatic colon cancer metastases induces VCAM-1 expression and T-cell recruitment
Authors: G. Mazzolini, I. Narvaiza, M. Bustos, I. Gabari, M. Duarte, R. Bilbao, C. Qian, J. Prieto, I. Melero
Journal: Journal of Hepatology (2001)
Flow Antagonizes TNF-α Signaling in Endothelial Cells by Inhibiting Caspase-Dependent PKCζ Processing
Authors: Gwenaele Garin, Jun-ichi Abe, Amy Mohan, Weimin Lu, Chen Yan, Andrew C. Newby, Arshad Rhaman, Bradford C. Berk
Journal: Circulation Research (2007)

Unidirectional laminar flow is atheroprotective, in part by inhibiting cytokine-mediated endothelial cell (EC) inflammation and apoptosis. Previously, we showed that flow inhibited TNF-alpha signaling by preventing activation of JNK. Recently, PKCzeta was identified as the PKC isoform most strongly regulated by flow pattern, with increased PKCzeta activity in regions of disturbed flow versus unidirectional flow. Interestingly, PKCzeta is cleaved by caspases after TNF-alpha stimulation to generate a 50-kDa truncated form (CATzeta, catalytic domain of PKCzeta) with a higher kinase activity than the full-length protein. We hypothesized that flow would inhibit TNF-alpha-mediated PKCzeta cleavage and thereby CATzeta formation. We found that PKCzeta activity was required for TNF-alpha-mediated JNK and caspase-3 activation in ECs. PKCzeta was rapidly cleaved to generate CATzeta in cultured bovine and human aortic ECs and in intact rabbit vessels stimulated with TNF-alpha. This truncated form of PKCzeta enhanced JNK and caspase-3 activation. Interestingly, PKCzeta cleavage was prevented by inhibitors of PKCzeta, JNK, and caspase activities, suggesting that these enzymes, via regulating CATzeta formation, modulate caspase-3 activity in ECs. Finally, we found that flow reduced caspase-dependent processing of PKCzeta and caspase-3 activation. These results define a novel role for PKCzeta as a shared signaling mediator for flow and TNF-alpha, and important for flow-mediated inhibition of proinflammatory and apoptotic events in ECs.
Warfarin therapy improves clinical outcome of Kawasaki disease patients with giant coronary aneurysm
Authors: Yoko Sugahara, Masahiro Ishii, Hirohiko Koizumi, Kimiyasu Egami, Hiromi Muta, Teiji Akagi, Hirohisa Kato, Toyojiro Matsuishi
Journal: Journal of the American College of Cardiology (2003)
PARTIAL PURIFICATION OF HUMAN PROTHROMBIN AND PROCONVERTIN: THEIR CHARACTERISTICS AND INTERACTION 1
Authors: Jessica H. Lewis, John H. Ferguson
Journal: Journal of Clinical Investigation (1953)

Independently and almost simultaneously a number of investigators recognized the fact that at least two plasma factors are important in the conversion of prothrombin to thrombin in the presence of tissue thromboplastin and calcium.Various names have been applied to these factors and, at a recent Macy Conference on blood clotting (1), most of the investigators agreed that they could be grouped into two entities as follows:Relatively labile factor Labile factor (Quick [2, 3]) Factor V, Proaccelerin (Owren [4, 5]) Plasma Ac globulin (Ware, Guest, and Seegers [6, 7]) Prothrombin accelerator (Fantl and Nance [8, 9]) Plasmatic co-factor of thromboplastin (Honorato, Rojas, and Ivanovic [10, 11]) Plasma prothrombin conversion factor (Stefanini [12]) Without prejudice and for the sake of simplicity, we have chosen to use the terms proposed by Owren, namely, proaccelerin and proconvertin for the plasma factors, and accelerin and convertin for the active (serum) factors.The investigations presented in this paper deal with a method for the partial separation of pro- thrombin and proconvertin from human plasma and the study of their interactions. MATERIALSImidazole buffer: pH 7.3 (26).Accelerin (Accelerator Globulin, AcG): Barium car- bonate treated beef serum prepared according to the method of Ware and Seegers (29).For the purposes of the present study this crude material served as a satis- factofy source of accelerin, free from prothrombin and proconvertin, and retained full potency on storage at -20°C .for one year or longer.In additional experiments, which will be reported separately, we have employed highly purified human proaccelerin.This material was not used in the present experiments as, due to its marked storage
Different stages of B cell differentiation in non-T acute lymphoblastic leukemia.
Authors: R Foa, N Migone, M Saitta, M T Fierro, M C Giubellino, P Lusso, L Cordero di Montezemolo, R Miniero, F Lauria
Journal: Journal of Clinical Investigation (1984)

Immunoglobulin heavy chain gene rearrangement was evaluated in 19 cases of acute lymphoblastic leukemia (ALL) and correlated with the immunological phenotypic expression on primary or phorbol diester (12-O-tetradecanoylphorbol-13-acetate [TPA])-induced cells. One case of common ALL (cALL), one case of T-ALL, and one undifferentiated acute leukemia that responded to anti-myeloid drugs after unsuccessful anti-lymphoid induction therapy, had germ line heavy chain genes. Rearranged immunoglobulin genes were instead found in 15 of the 16 cALL cases studied and in a case of non-T, non-B, non-common ("null") ALL, which suggested the B cell origin of the neoplastic cells. All cases bearing a heavy chain gene rearrangement were HLA-DR positive. However, the unique cALL case with a germ line configuration was also HLA-DR positive, which confirmed that both the cALL antigen and HLA-DR antigen were not per se expression of B cell commitment. On the other hand, a complete search for B cell-related markers (BA-1 and B1 monoclonal antibodies, as well as cytoplasmic immunoglobulins [CyIg]) in the cALL cases showed that at least one B cell marker could be detected either on primary or on TPA-induced cells in all cases in which a gene rearrangement had occurred. Incubation with TPA allowed the detection of one B cell marker in a case in which the primary cells were negative, and increased the expression of B cell markers in all but one of the cALLs tested. The only cALL case that was not rearranged expressed no B cell markers either on primary or on TPA-induced cells. The non-T, non-B, non-common ("null") case that was rearranged also showed no phenotypic evidence of B cell markers on primary and induced cells. These findings indicate that: (a) practically all cases of cALL appear to be of B cell origin as shown by gene rearrangement analysis; (b) DNA studies are relevant for a more precise characterization of individual cases of undifferentiated acute leukemia; (c) a complete survey for B cell markers may establish the B cell origin of the cALL blasts, as long as the analysis on primary cells is complemented by differentiation induction assessment; and (d) most cases of non-T ALL appear to be characterized by the expansion of neoplastic cells "frozen" at different levels along the B cell differentiation pathway, the first detectable marker being heavy chain gene rearrangement, followed by BA-1, B1, and CyIg expression.
Association Between Timeliness of Reperfusion Therapy and Clinical Outcomes in ST-Elevation Myocardial Infarction
Authors: Laurie Lambert
Journal: JAMA (2010)

<h3>Context</h3>Guidelines emphasize the importance of rapid reperfusion of patients with ST-elevation myocardial infarction (STEMI) and specify a maximum delay of 30 minutes for fibrinolysis and 90 minutes for primary percutaneous coronary intervention (PPCI). However, randomized trials and selective registries are limited in their ability to assess the effect of timeliness of reperfusion on outcomes in real-world STEMI patients.<h3>Objectives</h3>To obtain a complete interregional portrait of contemporary STEMI care and to investigate timeliness of reperfusion and outcomes.<h3>Design, Setting, and Patients</h3>Systematic evaluation of STEMI care for 6 months during 2006-2007 in 80 hospitals that treated more than 95% of patients with acute myocardial infarction in the province of Quebec, Canada (population, 7.8 million).<h3>Main Outcome Measures</h3>Death at 30 days and at 1 year and the combined end point of death or hospital readmission for acute myocardial infarction or congestive heart failure at 1 year by linkage to Quebec's medicoadministrative databases.<h3>Results</h3>Of 1832 patients treated with reperfusion, 392 (21.4%) received fibrinolysis and 1440 (78.6%) received PPCI. Fibrinolysis was untimely (&gt;30 minutes) in 54% and PPCI was untimely (&gt;90 minutes) in 68%. Death or readmission for acute myocardial infarction or heart failure at 1 year occurred in 13.5% of fibrinolysis patients and 13.6% of PPCI patients. When the 2 treatment groups were combined, patients treated outside of recommended delays had an adjusted higher risk of death at 30 days (6.6% vs 3.3%; odds ratio [OR], 2.14; 95% confidence interval [CI], 1.21-3.93) and a statistically nonsignificant increase in risk of death at 1 year (9.3% vs 5.2%; OR, 1.61; 95% CI, 1.00-2.66) compared with patients who received timely treatment. Patients treated outside of recommended delays also had an adjusted higher risk for the combined outcome of death or hospital readmission for congestive heart failure or acute myocardial infarction at 1 year (15.0% vs 9.2%; OR, 1.57; 95% CI, 1.08-2.30). At the regional level, after adjustment, each 10% increase in patients treated within the recommended time was associated with a decrease in the region-level odds of overall 30-day mortality (OR, 0.80; 95% CI, 0.65-0.98).<h3>Conclusion</h3>Among patients in Quebec with STEMI, reperfusion delivered outside guideline-recommend delays was associated with significantly increased 30-day mortality, a statistically nonsignificant increase in 1-year mortality, and significantly increased risk of the composite of mortality or readmission for acute myocardial infarction or heart failure at 1 year.
A Crucial Role for p90RSK-Mediated Reduction of ERK5 Transcriptional Activity in Endothelial Dysfunction and Atherosclerosis
Authors: Nhat-Tu Le, Kyung-Sun Heo, Yuichiro Takei, Hakjoo Lee, Chang-Hoon Woo, Eugene Chang, Carolyn McClain, Cheryl Hurley, Xin Wang, Faqian Li, Haodong Xu, Craig Morrell, Mark A. Sullivan, Michael S. Cohen, Iana M. Serafimova, Jack Taunton, Keigi Fujiwara, Jun-ichi Abe
Journal: Circulation (2012)

Background— Diabetes mellitus is a major risk factor for cardiovascular mortality by increasing endothelial cell (EC) dysfunction and subsequently accelerating atherosclerosis. Extracellular-signal regulated kinase 5 (ERK5) is activated by steady laminar flow and regulates EC function by increasing endothelial nitric oxide synthase expression and inhibiting EC inflammation. However, the role and regulatory mechanisms of ERK5 in EC dysfunction and atherosclerosis are poorly understood. Here, we report the critical role of the p90 ribosomal S6 kinase (p90RSK)/ERK5 complex in EC dysfunction in diabetes mellitus and atherosclerosis. Methods and Results— Inducible EC-specific ERK5 knockout (ERK5-EKO) mice showed increased leukocyte rolling and impaired vessel reactivity. To examine the role of endothelial ERK5 in atherosclerosis, we used inducible ERK5-EKO-LDLR −/− mice and observed increased plaque formation. When activated, p90RSK associated with ERK5, and this association inhibited ERK5 transcriptional activity and upregulated vascular cell adhesion molecule 1 expression. In addition, p90RSK directly phosphorylated ERK5 S496 and reduced endothelial nitric oxide synthase expression. p90RSK activity was increased in diabetic mouse vessels, and fluoromethyl ketone-methoxyethylamine, a specific p90RSK inhibitor, ameliorated EC-leukocyte recruitment and diminished vascular reactivity in diabetic mice. Interestingly, in ERK5-EKO mice, increased leukocyte rolling and impaired vessel reactivity were resistant to the beneficial effects of fluoromethyl ketone-methoxyethylamine, suggesting a critical role for endothelial ERK5 in mediating the salutary effects of fluoromethyl ketone-methoxyethylamine on endothelial dysfunction. Fluoromethyl ketone-methoxyethylamine also inhibited atherosclerosis formation in ApoE −/− mice. Conclusions— Our study highlights the importance of the p90RSK/ERK5 module as a critical mediator of EC dysfunction in diabetes mellitus and atherosclerosis formation, thus revealing a potential new target for therapeutic intervention.
Inhaled NO for Preterm Infants — Getting to Yes?
Authors: Ann R. Stark
Journal: New England Journal of Medicine (2006)

Preterm birth, especially at an extremely low gestational age, is often perilous. Despite improved survival associated with contemporary neonatal intensive care, more than one third of survivors with a birth weight of less than 1250 g have bronchopulmonary dysplasia (also known as chronic lung disease of prematurity), usually defined as a need for supplemental oxygen at 36 weeks of postmenstrual age. At least 10 to 15 percent of these infants also show ultrasonographic evidence of brain injury in the neonatal period. The two conditions often coexist and are associated with impaired neurodevelopment.The majority of infants born at an extremely . . .
Antibody-Associated Lymphotoxin in Acute Infection
Authors: Shih-Wen Huang, Doris B. Lattos, Donald B. Nelson, Kenneth Reeb, Richard Hong
Journal: Journal of Clinical Investigation (1973)

Five pediatric patients who were known to be previously healthy acutely developed lymphopenia during various viral or mycoplasma infections. In one case, fatal generalized varicella occurred and in another, severe toxic epidermal necrolysis ensued. To further investigate this phenomenon, a study was done to determine the incidence of and elucidate the pathogenesis of lymphopenia occurring during the acute phase of viral or mycoplasma infections. Acute and convalescent sera from patients with viral or mycoplasma infection and children immunized with live measles virus were screened for lymphocytotoxic activity against normal lymphocytes by the microcytotoxicity method of Terasaki and McClelland (1). Sera with lymphocytotoxic activity were found in 15 of 48 cases of viral infections, 4 of 22 mycoplasma infections, and 1 of 11 measles virus immunized persons. All those who had sera which were cytotoxic to lymphocytes in vitro had lymphopenia. The lymphocytotoxic activity resided in 19S fractions in 8 of 11 positive sera while the remaining 3 had activity both in 19S and 7S fractions and could be completely removed by absorption with antilight chain antiserum. The cytotoxic activities were all complement-dependent and were greater at 37 degrees C than at 4 degrees C. The significance of acute acquired immunologic deficiency due to the development of antibody-associated lymphotoxin (AbAL) during acute infections is discussed and five cases having more severe clinical manifestations are presented (Appendix).