tbuckley/cabot-search huggingface dataset:
Augmentation of hypoxic pulmonary vasoconstriction in the isolated perfused rat lung by in vitro antagonists of endothelium-dependent relaxation.
Authors: V L Brashers, M J Peach, C E Rose
Journal: Journal of Clinical Investigation (1988)

The role of the endothelium in hypoxic constriction of the intact pulmonary vascular bed has not been clearly elucidated. To test for a possible role for endothelium-derived relaxing factor(s) (EDRF) in the hypoxic pressor response, isolated, whole blood-perfused rat lungs from male Sprague-Dawley rats treated with meclofenamate were prepared. Three protocols were performed, including: (a) normal saline (control); (b) the putative EDRF inhibitors, eicosatetraynoic acid (ETYA, 1 X 10(-4) M) or nordihydroguaiaretic acid (NDGA, 1 X 10(-4) M) versus vehicle DMSO; and (c) the putative EDRF inhibitor hydroquinone (HQ, 1 X 10(-4) M) versus vehicle ethyl alcohol (ETOH). The pulmonary pressor response to angiotensin II (Ang II, 0.25 micrograms) injections alternated with 6-min periods of hypoxic ventilation (3% O2, 5% CO2) was measured before and after the administration of saline, inhibitors, or vehicles. The administration of the EDRF inhibitors ETYA, NDGA, and HQ resulted in a marked accentuation of the hypoxic pressor response that was not seen in the controls (P less than 0.05). In separate experiments, lungs precontracted with norepinephrine (1 X 10(-6) M) were pretreated with edrophonium (1 X 10(-4) M) and then observed for endothelium-dependent vasodilator responses to acetylcholine at increasing doses (1 X 10(-7)-1 X 10(-4) M). Administration of ETYA, NDGA, or HQ abrogated the observed vasodilatation to acetylcholine, which was not seen with vehicles alone (P less than 0.01). These studies suggest an important role for the endothelium in pulmonary vascular responsiveness to alveolar hypoxia through possible release of a relaxing factor(s) that attenuates the degree of pulmonary arterial constriction.
Arsenic: Signal Transduction, Transcription Factor, and Biotransformation Involved in Cellular Response and Toxicity
Authors: Yoshito Kumagai, Daigo Sumi
Journal: The Annual Review of Pharmacology and Toxicology (2006)

Arsenic is a naturally occurring metalloid that causes oxidative stress. Exposure of humans, experimental animals, and cultured cells to arsenic results in a variety of diverse health effects, dysfunction of critical enzymes, and cell damage. In this context, one area of arsenic study has been the role of its metabolism. Like organic chemicals, arsenic undergoes reduction, methylation, and glutathione conjugation to yield polar metabolites that are substrates for transporters. These events suggest that transcription factor(s) controlling the upregulation of antioxidant proteins, Phase II xenobiotic-metabolizing enzymes, and Phase III transporters should affect arsenic-mediated oxidative stress and the steady-state level of arsenic in the cells. In this review, we summarize recent progress in arsenic toxicity in terms of disrupted signal transduction cascades, the transcription factors involved, and arsenic biotransformation, including a novel pathway.
Increased Mortality, Postoperative Morbidity, and Cost After Red Blood Cell Transfusion in Patients Having Cardiac Surgery
Authors: Gavin J. Murphy, Barnaby C. Reeves, Chris A. Rogers, Syed I.A. Rizvi, Lucy Culliford, Gianni D. Angelini
Journal: Circulation (2007)

Background— Red blood cell transfusion can both benefit and harm. To inform decisions about transfusion, we aimed to quantify associations of transfusion with clinical outcomes and cost in patients having cardiac surgery. Methods and Results— Clinical, hematology, and blood transfusion databases were linked with the UK population register. Additional hematocrit information was obtained from intensive care unit charts. Composite infection (respiratory or wound infection or septicemia) and ischemic outcomes (myocardial infarction, stroke, renal impairment, or failure) were prespecified as coprimary end points. Secondary outcomes were resource use, cost, and survival. Associations were estimated by regression modeling with adjustment for potential confounding. All adult patients having cardiac surgery between April 1, 1996, and December 31, 2003, with key exposure and outcome data were included (98%). Adjusted odds ratios for composite infection (737 of 8516) and ischemic outcomes (832 of 8518) for transfused versus nontransfused patients were 3.38 (95% confidence interval [CI], 2.60 to 4.40) and 3.35 (95% CI, 2.68 to 4.35), respectively. Transfusion was associated with increased relative cost of admission (any transfusion, 1.42 times [95% CI, 1.37 to 1.46], varying from 1.11 for 1 U to 3.35 for &gt;9 U). At any time after their operations, transfused patients were less likely to have been discharged from hospital (hazard ratio [HR], 0.63; 95% CI, 0.60 to 0.67) and were more likely to have died (0 to 30 days: HR, 6.69; 95% CI, 3.66 to 15.1; 31 days to 1 year: HR, 2.59; 95% CI, 1.68 to 4.17; &gt;1 year: HR, 1.32; 95% CI, 1.08 to 1.64). Conclusions— Red blood cell transfusion in patients having cardiac surgery is strongly associated with both infection and ischemic postoperative morbidity, hospital stay, increased early and late mortality, and hospital costs.
Radiological study of pleural changes in relation to mesothelioma in Turkey.
Authors: G Hillerdal, Y I Baris
Journal: Thorax (1983)

In some villages in central Turkey pleural changes occur as a result of environmental exposure to mineral fibres. In most cases the fibre is asbestos but in some cases the non-asbestos fibre erionite, a zeolite, is responsible. The incidence of malignant mesothelioma is much higher in "erionite villages" than in "asbestos villages" despite similar frequencies of pleural changes. In this study chest radiographs from 466 people from asbestos villages, 549 from erionite villages, and 382 controls were compared. The frequency of pleural calcification was about the same in the two groups of villages studied, but the minor fissures were visible to a greater degree in erionite cases. In people from erionite villages "atypical" pleural calcification, due to calcification of the visceral rather than the parietal pleura, was more common. These differences may indicate that the fibres have different lengths and diameters.
Impact of Prosthesis-Patient Mismatch on Cardiac Events and Midterm Mortality After Aortic Valve Replacement in Patients With Pure Aortic Stenosis
Authors: Giordano Tasca, Zen Mhagna, Silvano Perotti, Pietro Berra Centurini, Tony Sabatini, Andrea Amaducci, Federico Brunelli, Marco Cirillo, Margherita Dalla Tomba, Eugenio Quiani, Giovanni Troise, Philippe Pibarot
Journal: Circulation (2006)

Background— Prosthesis-patient mismatch (PPM) occurs when the effective orifice area (EOA) of the prosthesis being implanted is too small in relation to body size, thus causing abnormally high transvalvular pressure gradients. The objective of this study was to examine the midterm impact of PPM on overall mortality and cardiac events after aortic valve replacement in patients with pure aortic stenosis. Methods and Results— The indexed EOA (EOAi) was estimated for each type and size of prosthesis being implanted in 315 consecutive patients with pure aortic stenosis. PPM was defined as an EOAi ≤0.80 cm 2 /m 2 and was correlated with overall mortality and cardiac events. PPM was present in 47% of patients. The 5-year overall survival and cardiac event-free survival were 82±3% and 75±4%, respectively, in patients with PPM compared with 93±3% and 87±4% in patients with no PPM ( P ≤0.01). In multivariate analysis, PPM was associated with a 4.2-fold (95% CI, 1.6 to 11.3) increase in the risk of overall mortality and 3.2-fold (95% CI, 1.5 to 6.8) increase in the risk of cardiac events. The other independent risk factors were history of heart failure, NHYA class III-IV, severe left ventricular hypertrophy, and absence of normal sinus rhythm before operation. Conclusions— PPM is an independent predictor of cardiac events and midterm mortality in patients with pure aortic stenosis undergoing aortic valve replacement. As opposed to other risk factors, PPM may be avoided or its severity may be reduced with the use of a preventive strategy at the time of operation.
GAMMA GLOBULIN METABOLISM IN RABBITS DURING THE ANAMNESTIC RESPONSE
Authors: Evangelos A. Catsoulis, Edward C. Franklin, Murray Oratz, Marcus A. Rothschild
Journal: The Journal of Experimental Medicine (1964)

1. Gamma globulin metabolism and distribution were studied employing rabbit gamma globulin (RGG)I(131) 24 times in 13 control rabbits. Similar studies were performed before and during the ananmestic response in 4 rabbits previously sensitized with a polyvalent pneumococcal vaccine. 2. During the ananmestic response, gamma-globulin levels increased from 1.0 to 6.0 gm/100 ml, and the gamma-globulin pool increased from 0.7 to 4.7 gm/kg. There was no change in the intravascular-extravascular partition of gamma globulin. 3. Gamma globulin degradation increased from 0.06 to 0.33 gm/kg/day during the 28 days of the immunization period while gamma globulin synthesis increased even further to average 0.47 gm/kg/day. Following the attainment of elevated gamma globulin levels the fractional rate of RGG-I(131) turnover increased from 8.0 to 12.5 per cent/day. 4. No differences were noted in the metabolism of homologous or autologous gamma globulin regardless of the allotypic specificities.
Patterns and Correlates of Local Therapy for Women With Ductal Carcinoma-In-Situ
Authors: Steven J. Katz, Paula M. Lantz, Nancy K. Janz, Angela Fagerlin, Kendra Schwartz, Lihua Liu, Dennis Deapen, Barbara Salem, Indu Lakhani, Monica Morrow
Journal: Journal of Clinical Oncology (2005)

Purpose Concerns have been raised about the quality of treatment for women with ductal carcinoma-in-situ (DCIS) because persistent high rates of mastectomy suggest overtreatment, whereas lower than expected rates of radiation therapy after breast-conserving surgery (BCS) suggest undertreatment. Patients and Methods All women with DCIS diagnosed in 2002 and who reported to the Detroit and Los Angeles Surveillance, Epidemiology, and End Results (SEER) registries were identified and surveyed shortly after receipt of surgery (response rate, 79.7%; n = 817). Analyses were restricted to patients with DCIS (n = 659) indicated by SEER stage data. Results Only 14.0% of patients at lowest risk of recurrence (based on tumor size and histologic grade) received a mastectomy compared with 22.8% and 52.6% of patients at intermediate and highest risk (P &lt; .001). Only 13.1% of patients who were not influenced or slightly influenced by concerns about recurrence received mastectomy compared with 48.8% of women who were greatly influenced by this concern (P &lt; .001). A between-geographic site difference in receipt of radiation after BCS was observed for the lowest risk group (38.9% in Los Angeles v 70.5% in Detroit) but not for the highest risk group (80.2% in Los Angeles v 85.9% in Detroit, P = .006 for site and risk group differences). Between-site differences in receipt of radiation after BCS were consistent with patient recall of surgeon discussions about treatment. Conclusion Surgeons are tailoring their recommendations for local therapy options for DCIS based on important clinical factors. Patient attitudes also play an important role in treatment decisions. The substantial influence of both surgeon opinion and patient attitudes should temper concerns about the quality of treatment for women with DCIS.
Problems and advantages of an observational data base approach to evaluating the effect of therapy on outcome.
Authors: R A Rosati, K L Lee, R M Califf, D B Pryor, F E Harrell
Journal: Circulation (1982)

In this report, we summarize the strengths and problems of an observational data base approach to evaluating therapy and studying patient outcomes in long-term chronic disease. Because this approach includes a greater spectrum of patients than randomized clinical trials, it offers a definite advantage with regard to the elucidation of prognostic factors and the application of results to specific patients. The major difficulty with the observational data base approach is that the important prognostic factors must be known for treatment comparisons to be valid. Both the observational data base and randomized trial approaches are susceptible to criticism because the multiple comparisons and multiple experiments usually involved make the results of any one study not definitive. Either approach is useful in generating or confirming a hypothesis about particular subgroups. Regardless of the method used, proof that a particular therapy increases survival in any group or subgroup of patients with coronary artery disease usually requires confirmation by multiple studies. Finally, observational data base approach, because it capitalizes on data generated and paid for in the patient care process, offers the most feasible approach for evaluating whether changes in prognosis are occurring over time and whether such changes are independent of the mix of the patient population.
Cell-mediated immune reactivity in liver disease
Authors: P. A. Bacon, H. Berry, R. Bown
Journal: Gut (1972)

Cell-mediated immunity has been investigated using the leucocyte migration test in 32 patients with chronic active hepatitis or primary biliary cirrhosis. Twenty-six (75%) showed reactivity to liver extract. At least two antigens are involved. Cell-mediated reactivity was confirmed in some cases using lymphocyte `blast9 transformation. There was no correlation with the presence of auto-antibodies. Cell-mediated immunity to parotid extract was shown in 10 cases (28%). This is in accord with the occurrence of the sicca syndrome in liver disease, which has been confirmed in this study.
Radiofrequency Catheter Ablation of Chronic Atrial Fibrillation Guided by Complex Electrograms
Authors: Hakan Oral, Aman Chugh, Eric Good, Alan Wimmer, Sujoya Dey, Nitesh Gadeela, Sundar Sankaran, Thomas Crawford, Jean F. Sarrazin, Michael Kuhne, Nagib Chalfoun, Darryl Wells, Melissa Frederick, Jackie Fortino, Suzanne Benloucif-Moore, Krit Jongnarangsin, Frank Pelosi, Frank Bogun, Fred Morady
Journal: Circulation (2007)

Radiofrequency catheter ablation of atrial fibrillation (AF) guided by complex fractionated atrial electrograms has been reported to eliminate AF in a large proportion of patients. However, only a small number of patients with chronic AF have been included in previous studies.In 100 patients (mean age, 57+/-11 years) with chronic AF, radiofrequency ablation was performed to target complex fractionated atrial electrograms at the pulmonary vein ostial and antral areas, various regions of the left atrium, and the coronary sinus until AF terminated or all identified complex fractionated atrial electrograms were eliminated. Ablation sites consisted of > or = 1 pulmonary vein in 46% of patients; the left atrial septum, roof, or anterior wall in all; and the coronary sinus in 55%. During 14+/-7 months of follow-up after a single ablation procedure, 33% of patients were in sinus rhythm without antiarrhythmic drugs, 38% had AF, 17% had both AF and atrial flutter, 9% had persistent atrial flutter, and 3% had paroxysmal AF on antiarrhythmic drugs. A second ablation procedure was performed in 44% of patients. Pulmonary vein tachycardia was found in all patients in both previously targeted and nontargeted pulmonary veins. There were multiple macroreentrant circuits in the majority of patients with atrial flutter. At 13+/-7 months after the last ablation procedure, 57% of patients were in sinus rhythm without antiarrhythmic drugs, 32% had persistent AF, 6% had paroxysmal AF, and 5% had atrial flutter.Modest short-term efficacy is achievable with radiofrequency ablation of chronic AF guided by complex fractionated atrial electrograms, but only after a second ablation procedure in > 40% of patients. Rapid activity in the pulmonary veins and multiple macroreentrant circuits are common mechanisms of recurrent atrial arrhythmias.
Official American Thoracic Society Technical Standards: Flexible Airway Endoscopy in Children
Authors: Albert Faro, Robert E. Wood, Michael S. Schechter, Albin B. Leong, Eric Wittkugel, Kathy Abode, James F. Chmiel, Cori Daines, Stephanie Davis, Ernst Eber, Charles Huddleston, Todd Kilbaugh, Geoffrey Kurland, Fabio Midulla, David Molter, Gregory S. Montgomery, George Retsch-Bogart, Michael J. Rutter, Gary Visner, Stephen A. Walczak, Thomas W. Ferkol, Peter H. Michelson
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Flexible airway endoscopy (FAE) is an accepted and frequently performed procedure in the evaluation of children with known or suspected airway and lung parenchymal disorders. However, published technical standards on how to perform FAE in children are lacking.The American Thoracic Society (ATS) approved the formation of a multidisciplinary committee to delineate technical standards for performing FAE in children. The committee completed a pragmatic synthesis of the evidence and used the evidence synthesis to answer clinically relevant questions.There is a paucity of randomized controlled trials in pediatric FAE. The committee developed recommendations based predominantly on the collective clinical experience of our committee members highlighting the importance of FAE-specific airway management techniques and anesthesia, establishing suggested competencies for the bronchoscopist in training, and defining areas deserving further investigation.These ATS-sponsored technical standards describe the equipment, personnel, competencies, and special procedures associated with FAE in children.
Abnormal germinal center reactions in systemic lupus erythematosus demonstrated by blockade of CD154-CD40 interactions
Authors: Amrie C. Grammer, Rebecca Slota, Randy Fischer, Hanan Gur, Hermann Girschick, Cheryl Yarboro, Gabor G. Illei, Peter E. Lipsky
Journal: Journal of Clinical Investigation (2003)

To determine the role of CD154-CD40 interactions in the B cell overactivity exhibited by patients with active systemic lupus erythematosus (SLE), CD19+ peripheral B cells were examined before and after treatment with humanized anti-CD154 mAb (BG9588, 5c8). Before treatment, SLE patients manifested activated B cells that expressed CD154, CD69, CD38, CD5, and CD27. Cells expressing CD38, CD5, or CD27 disappeared from the periphery during treatment with anti-CD154 mAb, and cells expressing CD69 and CD154 disappeared from the periphery during the post-treatment period. Before treatment, active-SLE patients had circulating CD38bright Ig-secreting cells that were not found in normal individuals. Disappearance of this plasma cell subset during treatment was associated with decreases in anti–double-stranded DNA (anti-dsDNA) Ab levels, proteinuria, and SLE disease activity index. Consistent with this finding, peripheral B cells cultured in vitro spontaneously proliferated and secreted Ig in a manner that was inhibited by anti-CD154 mAb. Finally, the CD38+/++IgD+, CD38+++, and CD38+IgD– B cell subsets present in the peripheral blood also disappeared following treatment with humanized anti-CD154. Together, these results indicate that patients with active lupus nephritis exhibit abnormalities in the peripheral B cell compartment that are consistent with intensive germinal center activity, are driven via CD154-CD40 interactions, and may reflect or contribute to the propensity of these patients to produce autoantibodies.
Inhibition of Class I Phosphoinositide 3-Kinase Activity Impairs Proliferation and Triggers Apoptosis in Acute Promyelocytic Leukemia without Affecting Atra-Induced Differentiation
Authors: Clotilde Billottet, Lalita Banerjee, Bart Vanhaesebroeck, Asim Khwaja
Journal: Cancer Research (2009)

We have investigated the role of phosphoinositide 3-kinases (PI3Ks) in the in vitro pathophysiology of acute promyelocytic leukemia (APL) and in the response to treatment with all-trans-retinoic-acid (ATRA), utilizing a range of novel inhibitors that target individual or all catalytic class I isoforms of PI3K (p110alpha, p110beta, p110delta, and p110gamma). ATRA-induced phosphorylation of the Akt kinase and ribosomal S6 protein in APL cells was sensitive to class I PI3K, and p110beta or p110delta inhibitors, and to the mammalian target of rapamycin (mTOR) inhibitor rapamycin. In primary APL, inhibition of p110beta or p110delta triggered apoptosis in the absence or presence of ATRA. Class I PI3K inhibition could also reverse ATRA-induced protection of these cells against doxorubicin and arsenic trioxide, correlating with impaired induction of the antiapoptotic MCL-1 protein. The differentiation-inducing effects of ATRA were not dependent on class I PI3K/mTOR. In summary, class I PI3K signaling, mediated by p110beta and p110delta, plays an important role in basal and ATRA-induced cell survival mechanisms in APL. Addition of PI3K inhibitors to induction treatment regimens may provide therapeutic benefit.
KCNQ1 autoantibodies: another way to regulate IKs
Authors: Jordi Heijman, Dobromir Dobrev
Journal: Cardiovascular Research (2013)

This editorial refers to ‘Anti-KCNQ1 K+ channel autoantibodies increase I Ks current and are associated with QT interval shortening in dilated cardiomyopathy’ by J. Li et al. , pp. 496–503, this issue. 

A subset of patients with dilated cardiomyopathy (DCM) have been shown to carry increased levels of autoantibodies against β-adrenoceptors, muscarinic receptors, Na+–K+-ATPase, or troponin I.1–4 There is increasing evidence that these autoantibodies can have important electrophysiological consequences and may contribute to the arrhythmogenic risk of DCM patients.1 In this edition of Cardiovascular Research , Li et al .5 identify another potential electrophysiological target of autoantibodies by showing that a subset of patients with DCM has elevated autoantibodies against the extracellular pore region of KCNQ1, the α-subunit of the slowly activating delayed rectifier K+ current ( I Ks). Anti-KCNQ1 autoantibodies, present in ∼6% of DCM patients, increased I Ks in human embryonic kidney cells, and were associated with shortened QT intervals in seropositive patients. This interesting study adds important new insights to our understanding of the regulation and potential dysfunction of I Ks.

Although I Ks is small under basal conditions in isolated myocytes and contributes little to cardiac repolarization in this setting, it constitutes an important repolarization reserve that can be called upon when repolarization is compromised, for example, due to inhibition of the rapidly activating delayed rectifier K+ current, or due to reduced inactivation of L-type Ca2+ current following spontaneous diastolic Ca2+-release events.6, …
Nurse Staffing and NICU Infection Rates
Authors: Jeannette A. Rogowski, Douglas Staiger, Thelma Patrick, Jeffrey Horbar, Michael Kenny, Eileen T. Lake
Journal: JAMA Pediatrics (2013)

There are substantial shortfalls in nurse staffing in US neonatal intensive care units (NICUs) relative to national guidelines. These are associated with higher rates of nosocomial infections among infants with very low birth weights.