tbuckley/cabot-search huggingface dataset:
Blood flow velocity and systolic time intervals measured by pulsed Doppler ultrasound: reproducibility of measurements
Authors: T LANG-JENSEN
Journal: Cardiovascular Research (1987)

The reproducibility of measurements of blood flow velocity in the aorta and systolic time intervals using pulsed ultrasound Doppler was determined in 10 subjects. Measurements were made in both the ascending aorta and the aortic arch, and instant maximum as well as instant mean velocities were measured. The smallest variation was found when the maximum velocity was measured in the ascending aorta. The coefficient of variation in measurements was between 6.9% and 13.1%, when determined at intervals of 10-15 min. Again the smallest variation was when the maximum velocity was measured in the ascending aorta. The intraobserver variation was smaller than the interobserver variation (6.9% compared with 10.6%) in the ascending aorta. Both the intraobserver and interobserver variations in systolic time intervals were very small. The mean coefficients of variation were 1.7% for the pre-ejection period (PEP), 1.7% for left ventricular ejection time (LVET), 1.4% for electromechanical systole (QS2), and 2.9% for the PEP:LVET ratio. The mean values of pre-ejection period and left ventricular ejection time were 154 ms and 377 ms, which are a little longer and shorter respectively than measurements made by phonocardiography and pulse pressure monitoring, whereas QS2 was the same (531 ms). The interobserver variations were 2.6%, 2.0%, 1.4%, and 3.9% respectively. It is concluded that pulsed Doppler ultrasound is a reliable method of measuring blood flow velocity and systolic time intervals. Changes in blood flow velocity of 10-12% can be detected by this method.
Hypoglycemia Increases Serum Interleukin-6 Levels in Healthy Men and Women
Authors: Sarah Dotson, Roy Freeman, Hannah J. Failing, Gail K. Adler
Journal: Diabetes Care (2008)

Inflammation may have a major role in the pathogenesis and prognosis of critical illness. Hyperglycemia increases levels of the inflammatory cytokine interleukin-6 (IL-6) and is associated with increased risks of morbidity and mortality. Because hypoglycemia is also associated with adverse outcomes, we tested the hypothesis that hypoglycemia increases IL-6.Seventeen healthy men and women participated in hypoglycemic and euglycemic-hyperinsulinemic clamp studies (target blood glucose levels 2.7 and 5.0 mmol/l, respectively), separated by 1-3 months. IL-6, ACTH, and cortisol were measured at baseline and at 45, 75, 105, and 135 min after initiation of the insulin infusion.IL-6, ACTH, and cortisol levels increased significantly (P < 0.0001) during hypoglycemia but not euglycemia. IL-6 increased from mean +/- SEM 1.0 +/- 0.2 pg/ml at baseline to 2.6 +/- 0.2 pg/ml after 135 min of hypoglycemia, whereas IL-6 levels were unchanged during euglycemia.Hypoglycemia increases IL-6 levels in healthy individuals.
Lower Bronchodilator Responsiveness in Puerto Rican than in Mexican Subjects with Asthma
Authors: Esteban González Burchard, Pedro C. Avila, Sylvette Nazario, Jesus Casal, Alfonso Torres, Jose R. Rodriguez-Santana, Monica Toscano, Jody Senter Sylvia, MariaElena Alioto, Michael Salazar, Ivan Gomez, Joanne K. Fagan, Jorge Salas, Craig Lilly, Henry Matallana, Elad Ziv, Richard Castro, Moises Selman, Rocio Chapela, Dean Sheppard, Scott T. Weiss, Jean G. Ford, Homer A. Boushey, William Rodriguez-Cintron, Jeffrey M. Drazen, Edwin K. Silverman
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

In the United States, Puerto Ricans and Mexicans have the highest and lowest asthma prevalence, morbidity, and mortality, respectively. To determine whether ethnicity-specific differences in therapeutic response, clinical response, and/or genetic factors contribute to differences in asthma outcomes, we compared asthma-related clinical characteristics among 684 Mexican and Puerto Rican individuals with asthma recruited from San Francisco, New York City, Puerto Rico, and Mexico City. Puerto Ricans with asthma had reduced lung function, greater morbidity, and longer asthma duration than did Mexicans with asthma. Bronchodilator responsiveness, measured as percentage change from baseline FEV1, was significantly lower among Puerto Ricans with asthma than among Mexicans with asthma. Puerto Ricans with asthma had on average 7.3% (95% confidence interval [CI], 4.6 to 9.9; p < 0.001) lower bronchodilator reversibility in FEV1, higher risk of an emergency department visit in the previous year (odds ratio, 2.63; 95% CI, 1.6 to 4.3; p < 0.001), and of previous hospitalization for asthma (odds ratio, 1.94; 95% CI, 1.2 to 3.2; p = 0.009) than Mexicans. Subgroup analysis corroborated that Puerto Ricans with asthma had more severe disease than did Mexicans on the basis of lung function measurements, responsiveness to beta2-adrenergic agonists, and health care use. We conclude that Puerto Ricans with asthma respond less to albuterol than do Mexicans with asthma. These findings underscore the need for additional research on racial/ethnic differences in asthma morbidity and response to therapy.
JAK–STAT Pathway Activation in Malignant and Nonmalignant Cells Contributes to MPN Pathogenesis and Therapeutic Response
Authors: Maria Kleppe, Minsuk Kwak, Priya Koppikar, Markus Riester, Matthew Keller, Lennart Bastian, Todd Hricik, Neha Bhagwat, Anna Sophia McKenney, Efthymia Papalexi, Omar Abdel-Wahab, Raajit Rampal, Sachie Marubayashi, Jonathan J. Chen, Vincent Romanet, Jordan S. Fridman, Jacqueline Bromberg, Julie Teruya-Feldstein, Masato Murakami, Thomas Radimerski, Franziska Michor, Rong Fan, Ross L. Levine
Journal: Cancer Discovery (2015)

Abstract The identification of JAK2/MPL mutations in patients with myeloproliferative neoplasms (MPN) has led to the clinical development of JAK kinase inhibitors, including ruxolitinib. Ruxolitinib reduces splenomegaly and systemic symptoms in myelofibrosis and improves overall survival; however, the mechanism by which JAK inhibitors achieve efficacy has not been delineated. Patients with MPN present with increased levels of circulating proinflammatory cytokines, which are mitigated by JAK inhibitor therapy. We sought to elucidate mechanisms by which JAK inhibitors attenuate cytokine-mediated pathophysiology. Single-cell profiling demonstrated that hematopoietic cells from myelofibrosis models and patient samples aberrantly secrete inflammatory cytokines. Pan-hematopoietic Stat3 deletion reduced disease severity and attenuated cytokine secretion, with similar efficacy as observed with ruxolitinib therapy. In contrast, Stat3 deletion restricted to MPN cells did not reduce disease severity or cytokine production. Consistent with these observations, we found that malignant and nonmalignant cells aberrantly secrete cytokines and JAK inhibition reduces cytokine production from both populations. Significance: Our results demonstrate that JAK–STAT3-mediated cytokine production from malignant and nonmalignant cells contributes to MPN pathogenesis and that JAK inhibition in both populations is required for therapeutic efficacy. These findings provide novel insight into the mechanisms by which JAK kinase inhibition achieves therapeutic efficacy in MPNs. Cancer Discov; 5(3); 316–31. ©2015 AACR. See related commentary by Belver and Ferrando, p. 234 This article is highlighted in the In This Issue feature, p. 213
Role of Surgery in Ovarian Carcinoma
Authors: Amanda Nickles Fader, Peter G. Rose
Journal: Journal of Clinical Oncology (2007)

Surgery plays a critical role in the optimal management of all stages of ovarian carcinoma. In apparent early-stage ovarian cancer, a comprehensive surgical evaluation allows stratification of patients into low- and high-risk categories. Low-risk patients may be candidates for fertility-sparing surgery and can safely avoid chemotherapy and be observed. Treatment of patients with high-risk early- or advanced-stage ovarian cancer usually requires a combined modality approach. Although it is well known that epithelial ovarian cancer is moderately chemosensitive, what distinguishes it most from other metastatic solid tumors is that surgical cytoreduction of tumor volume is highly correlated with prolongation of patient survival. Procedures such as radical pelvic surgery, bowel resection, and aggressive upper abdominal surgery are commonly required to achieve optimal cytoreduction. Women who develop recurrent disease may be eligible for a secondary cytoreductive surgery or may require a surgical intervention to palliate disease-related symptoms. For women at high risk of ovarian cancer, prophylactic bilateral salpingo-oophorectomy significantly reduces the incidence of this disease. The purpose of this article is to provide a comprehensive review of the surgical management of ovarian carcinoma. The roles of primary, interval, and secondary cytoreductive surgeries; second-look procedures; and palliative surgery are reviewed. The indications for fertility-sparing and minimally invasive surgery as well as the current guidelines for prophylactic surgery in high-risk mutation carriers are also discussed.
The fuzzy reality of perceived harms
Authors: Sara Konrath, Irene Cheung
Journal: Behavioral and Brain Sciences (2012)

Abstract We review two subjective (mis)perceptions that influence revenge and forgiveness systems. Individual differences predict more (e.g., narcissism) or less (e.g., empathy) revenge, with the opposite pattern for forgiveness. Moreover, differences in victim versus perpetrator perceptions can influence revenge and forgiveness systems, perpetuating never-ending cycles of revenge. These two examples point to the need for theories of revenge and forgiveness to address the role of cognitive and motivational biases in the functionality of such behavioral responses.
Effects of nisoldipine upon endothelial dysfunction following ischaemic and peroxidative injury in the perfused rat heart
Authors: M. M Yaghi, J. A Watts
Journal: Cardiovascular Research (1993)

Objective: Previous studies showed that treatment of hearts with nisoldipine improves recovery of cardiac function following ischaemia, improves reperfusion, and reduces the constrictor sensitivity to endothelin. The aim of the present study was to assess the reduction in vasodilator responses that occurs following ischaemia and reperfusion or after oxidative stress, and to determine whether nisoldipine treatment improves these dilator responses. Methods: Isolated perfused rat hearts were studied. Coronary vessels were constricted by the addition of U46619 and dilator responses were determined with the addition of acetylcholine (endothelium dependent) or glyceryl trinitrate (endothelium independent). Responses were compared before and after low flow ischaemia (20%, 30 min) and reperfusion (30 min), or treatment with tert-butyl hydroperoxide (tBHP) (0.9 mM, 12 min, 30 min wash). Results: The addition of U46619 caused a prolonged increase in perfusion pressure of 50 to 70 mm Hg which was not significantly different before and after treatment. Dilatation responses to acetylcholine were significantly reduced following ischaemia and reperfusion (34% of preischaemic values) or tBHP (47.6% of pre-tBHP values), while responses to glyceryl trinitrate were not significantly changed. In contrast, when hearts were perfused with nisoldipine, the responses to acetylcholine were significantly improved (88% of preischaemic values with 5 nM nisoldipine, and 68% to 78% of pre-tBHP values with 0.5 nM to 5 nM nisoldipine). Responses to acetylcholine following tBHP were not significantly improved when hearts were perfused with verapamil (5 nM 43.5%, 5 μM 32%, of pre-tBHP values), or diltiazem (5 nM 37%, 5 μM 31%, of pre-tBHP values). Conclusions: Ischaemia and reperfusion or oxidative stress reduced endothelium dependent responses, but not endothelium independent responses. Nisoldipine reduced the injury to endothelial cell function associated with ischaemia and reperfusion or oxidative stress. Cardiovascular Research 1993;27:990-996
Significance of Splanchnic Proteases in the Production of a Toxic Factor in Hemorrhagic Shock
Authors: Thomas M. Glenn, Allon M. Lefer
Journal: Circulation Research (1971)

The pathogenesis of circulatory shock has been previously associated with the plasma accumulation of a myocardial depressant factor (MDF). The plasma accumulation of MDF in cats subjected to hemorrhagic shock was associated with marked increases (P &lt;0.01) in activities of plasma cathepsins A-B. The pH optima for three of the five cathepsins were in the range of 4.8-5.2, a pH range close to that found intracellularly during shock. Moreover, pancreatic and hepatic tissue from these cats exhibited significant decreases in total specific activities for these enzymes, compared with minimal changes in heart, duodenum and spleen. Decreases in total pancreatic cathepsin activities were associated with marked ultrastructural changes in pancreatic acinar cells primarily characterized by vacuolization of the lysosomes. Incubation of homogenates of splanchnic viscera of unshocked dogs revealed that significant concentrations of MDF were produced only in incubated pancreatic homogenates. Infusion of MDF in amounts half that produced by a cat pancreas into intact anesthetized cats yielded a significant circulatory depression indicated by a progressive decline in cardiac output and mean arterial blood pressure and a 54% decrease in cardiac work performance within 60 minutes. These data indicate that substantial amounts of lysosomal proteases are released during shock and that they operate in a suitable pH range to account for the production of quantities of MDF that are sufficient to induce a marked degree of cardiac depression.
End of domestic asbestos exposure epidemic in Metsovo; N.W. Greece
Authors: Athena Gogali, Evaggelia Ntzani, Sofia Peristeri, Loukia Tzarouchi, Carmen Manda-Stachouli, Thomas Vadivoulis, George Dascalopoulos, Konstantinos Tsampoulas, Stavros Constantopoulos, Yotanna Dalavanga
Journal: European Respiratory Journal (2012)

INTRODUCTION: Metsovites had been exposed to tremolite asbestos from a whitewash (luto), used by all until 1940. This exposure has resulted in frequent pleural calcifications (PCs) and a mesothelioma epidemic, fading due to abandonment of luto.  We have reported that most older Metsovites have PCs in chest CT and asbestos bodies (ABs) in BAL. These parameters are used now in younger Metsovites to evaluate if those not exposed are free from signs of exposure.  MATERIALS & METHODS: 22 Metsovites age 30-49 had chest CTs and 8 of them BAL. Age was chosen because it takes 30 yrs for PCs to appear and because they were born between 1960-80 when luto use had declined considerably giving us the possibility to evaluate Metsovites who have lived all their life free of luto. Previous BAL studies of 7 age matched Metsovites were used as control. There were no similar control chest CTs. Therefore we studied all available (86) chest CTs of Metsovites over 30.  RESULTS: Only 3/22 had used luto (35,47,48 yo). All 8 BAL studies were negative, in contrast to the exposed control group, where 6/7 (85,7%) BAL studies showed ABs. Only one chest CT was positive for PCs (48yo: luto until 13yo). From the 86 chest CTs, 5 belonged in the 30-39 and 9 in 40-49 yo group. None of the 30-39yo group had PCs and none had used luto. There was one CT positive in the 40-49yo group (11%). He had used luto in childhood as was the case with 2/6 others of this group in which luto history was obtained.  CONCLUSION: There is no evidence of asbestos exposure in younger Metsovites who have not used luto. The domestic use of this tremolite-whitewash has been the only source of asbestos in Metsovo. Its abandonment has resulted in the end of this epidemic.
Pulmonary manifestations in adult patients with chronic granulomatous disease
Authors: Hélène Salvator, Nizar Mahlaoui, Emilie Catherinot, Elisabeth Rivaud, Benoit Pilmis, Raphael Borie, Bruno Crestani, Colas Tcherakian, Felipe Suarez, Bertrand Dunogue, Marie-Anne Gougerot-Pocidalo, Margarita Hurtado-Nedelec, Jean-François Dreyfus, Isabelle Durieu, Fanny Fouyssac, Olivier Hermine, Olivier Lortholary, Alain Fischer, Louis-Jean Couderc
Journal: European Respiratory Journal (2015)

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by failure of superoxide production in phagocytic cells. The disease is characterised by recurrent infections and inflammatory events, frequently affecting the lungs. Improvement of life expectancy now allows most patients to reach adulthood. We aimed to describe the pattern of pulmonary manifestations occurring during adulthood in CGD patients. This was a retrospective study of the French national cohort of adult patients (≥16 years old) with CGD. Medical data were obtained for 67 adult patients. Pulmonary manifestations affected two-thirds of adult patients. Their incidence was significantly higher than in childhood (mean annual rate 0.22 versus 0.07, p=0.01). Infectious risk persisted despite anti-infectious prophylaxis. Invasive fungal infections were frequent (0.11 per year per patient) and asymptomatic in 37% of the cases. They often required lung biopsy for diagnosis (10 out of 30). Noninfectious respiratory events concerned 28% of adult patients, frequently associated with a concomitant fungal infection (40%). They were more frequent in patients with the X-linked form of CGD. Immune-modulator therapies were required in most cases (70%). Respiratory manifestations are major complications of CGD in adulthood. Noninfectious pulmonary manifestations are as deleterious as infectious pneumonia. A specific respiratory monitoring is necessary.
Epidemiological studies in monitoring reproductive effects.
Authors: H K Taskinen
Journal: Environmental Health Perspectives (1993)

The possible hazards of occupational exposure on the reproductive health of workers is of great interest. In this review, epidemiological study designs suitable for reproductive studies and sources of outcome and exposure data are described with a few examples. Studies have been conducted on hormonal changes, semen quality, fertility, and various outcomes of pregnancy, e.g., spontaneous abortion, congenital malformations, perinatal mortality, birth weight, and health and development of the children. Also, sex distribution of children has been investigated as a possible risk indicator in some recent studies. In epidemiological studies, retrospective or prospective cohort design, case referent and nested case referent designs have been used. The validity of epidemiological studies depend on reliable data on the health effect and the exposure. The registers on congenital malformations and on births and other outcomes of pregnancy are useful sources of data for epidemiological studies. The coverage of the register and the accuracy of its contents should be known if the register is used for research. Personal interview of the worker is an important source of information, although recall problems may weaken the quality of the data. The reliability of the answers may be increased by using a few complementary questions on possible medical confirmation of the event. If both the interview and register data are available, the reliability of the information increases, the same concerns exposure information also. Examples of some conducted studies are given.
Electrophysiological Characterization of an Alternatively Processed ERG K <sup>+</sup> Channel in Mouse and Human Hearts
Authors: James P. Lees-Miller, Colleen Kondo, Li Wang, Henry J. Duff
Journal: Circulation Research (1997)

Abstract Mutants of HERG, the human form of ERG (the ether-a-go-go –related K + channel gene), are responsible for some forms of the long-QT syndrome, an abnormality of cardiac repolarization. HERG was cloned from brain and has properties similar but not identical to the rapidly activating component of the native cardiac K + channel current ( I Kr ). We identified in the mouse an alternatively processed form of ERG (MERG B) that is expressed abundantly in heart but only in trace amounts in brain. MERG B has a unique 36–amino acid NH 2 -terminal domain that is strongly basic and considerably shorter than the 376–amino acid NH 2 -terminal domain of HERG. When expressed in Xenopus oocytes, the kinetics of activation and deactivation of the MERG B current were best fit by a biexponential function, with the fast components dominant over the slow components. The fast component of activation had a mean τ value of 163±16 ms at −20 mV and 8±4 ms at +20 mV (n=4). The fast component of deactivation had a mean τ value of 145±29 ms at −20 mV and 12±4 ms at −90 mV (n=4). The MERG B current was blocked by the selective I Kr blocker, dofetilide, with an IC 50 of 54 nmol/L. In addition, we isolated HERG B, the human homologue of MERG B, which has electrophysiological characteristics qualitatively similar to those of MERG B. We have identified ERG B, an alternatively processed isoform of the ERG gene, expressed selectively in heart and with electrophysiological characteristics similar to those of native cardiac I Kr .
The changing face of commissioning in England
Authors: Martin Roland, Laura Brereton
Journal: Journal of the Royal Society of Medicine (2011)

The government's White Paper Equity and Excellence: Liberating the NHS1 introduces the most radical changes to the English NHS since its inception in 1948. These reforms include abolition of Primary Care Trusts, the current bodies that purchase healthcare, and Strategic Health Authorities, the regional management outposts of the Department of Health. Up to 70% of the NHS budget (£80bn) will instead be routed directly from a National Commissioning Board to consortia of GPs who will have responsibility for scoping and purchasing the majority of health services for their populations. An important caveat is that these changes only affect England: the divergence of the NHS between the four countries of the UK will increase, with Scotland in particular set against market-style reforms.
Glyoxalase 1 overexpression does not affect atherosclerotic lesion size and severity in ApoE−/− mice with or without diabetes
Authors: Nordin M.J. Hanssen, Olaf Brouwers, Marion J. Gijbels, Kristiaan Wouters, Erwin Wijnands, Jack P.M. Cleutjens, Jo G. De Mey, Toshio Miyata, Erik A. Biessen, Coen D.A. Stehouwer, Casper G. Schalkwijk
Journal: Cardiovascular Research (2014)

Advanced glycation end-products (AGEs) and their precursors have been associated with the development of atherosclerosis. We recently discovered that glyoxalase 1 (GLO1), the major detoxifying enzyme for AGE precursors, is decreased in ruptured human plaques, and that levels of AGEs are higher in rupture-prone plaques. We here investigated whether overexpression of human GLO1 in ApoE−/− mice could reduce the development of atherosclerosis. We crossed C57BL/6 ApoE−/− mice with C57BL/6 GLO1 overexpressing mice (huGLO1+/−) to generate ApoE−/− (n = 16) and ApoE−/− huGLO1+/− (n = 20) mice. To induce diabetes, we injected a subset with streptozotocin (STZ) to generate diabetic ApoE−/− (n = 8) and ApoE−/− huGLO1+/− (n = 13) mice. All mice were fed chow and sacrificed at 25 weeks of age. The GLO1 activity was three-fold increased in huGLO1+/− aorta, but aortic root lesion size and phenotype did not differ between mice with and without huGLO1+/− overexpression. We detected no differences in gene expression in aortic arches, in AGE levels and cytokines, in circulating cells, and endothelial function between ApoE−/− mice with and without huGLO1+/− overexpression. Although diabetic mice showed decreased GLO1 expression (P < 0.05) and increased lesion size (P < 0.05) in comparison with non-diabetic mice, GLO1 overexpression also did not affect the aortic root lesion size or inflammation in diabetic mice. In ApoE−/− mice with or without diabetes, GLO1 overexpression did not lead to decreased atherosclerotic lesion size or systemic inflammation. Increasing GLO1 levels does not seem to be an effective strategy to reduce glycation in atherosclerotic lesions, likely due to increased AGE formation through GLO1-independent mechanisms.