tbuckley/cabot-search huggingface dataset:
High Plasma 5-Hydroxyindole-3-Acetic Acid Concentrations in Subjects With Metabolic Syndrome
Authors: Michiaki Fukui, Muhei Tanaka, Hitoshi Toda, Mai Asano, Masahiro Yamazaki, Goji Hasegawa, Saeko Imai, Naoto Nakamura
Journal: Diabetes Care (2011)

Serotonin mediates vasoconstriction and induces the activation of platelets, which may promote atherosclerosis. The aim of this study was to investigate whether plasma 5-hydroxyindole-3-acetic acid (5-HIAA; a derivative end product of serotonin) concentrations are high in subjects with metabolic syndrome (MetS) and to investigate the relationship between plasma 5-HIAA concentrations and clinical and biochemical metabolic parameters.Plasma 5-HIAA concentrations were measured in 311 subjects (152 men and 159 women) recruited from the Oike Clinic, which provides regular health check-ups for employees. We evaluated the relationship between plasma 5-HIAA concentrations and clinical and biochemical metabolic parameters, including waist circumference, serum lipid concentrations, fasting plasma glucose, or blood pressure.Plasma 5-HIAA concentrations were higher in subjects with MetS than in those without, in both men (6.5 ± 4.4 vs. 4.9 ± 1.3 ng/mL, P < 0.005) and women (7.9 ± 6.5 vs. 5.2 ± 1.6 ng/mL, P < 0.005). In men, fasting plasma glucose (r = 0.197, P = 0.0146) was positively correlated, whereas HDL cholesterol (r = -0.217, P = 0.0071) was negatively correlated, with logarithmic (log) (plasma 5-HIAA concentrations). In women, triglycerides (r = 0.252, P = 0.0013) and fasting plasma glucose (r = 0.344, P < 0.0001) were positively correlated, whereas HDL cholesterol (r = -0.328, P < 0.0001) was negatively correlated, with log (5-HIAA concentrations). Furthermore, log (plasma 5-HIAA concentrations) were higher in subjects with more components of MetS.Plasma 5-HIAA concentrations are high in subjects with MetS, suggesting the potential importance of serotonin in the development of cardiovascular disease in MetS.
Predictors of Competing Mortality in Advanced Head and Neck Cancer
Authors: Loren K. Mell, James J. Dignam, Joseph K. Salama, Ezra E.W. Cohen, Blase N. Polite, Virag Dandekar, Amit D. Bhate, Mary Ellyn Witt, Daniel J. Haraf, Bharat B. Mittal, Everett E. Vokes, Ralph R. Weichselbaum
Journal: Journal of Clinical Oncology (2009)

PURPOSE Death from noncancer causes (competing mortality) is an important event in head and neck cancer, but studies identifying predictors of this event are lacking. We sought to identify predictors of competing mortality and develop a risk stratification model for competing events. PATIENTS AND METHODS Cohort study of 479 patients with stage III to IV carcinoma of the head and neck diagnosed between August 1993 and November 2004. Patients were treated on consecutive prospective clinical trials involving organ-preserving chemoradiotherapy and surgery. We used multivariable competing risks regression models to analyze factors associated with the cumulative incidence of competing mortality, locoregional and distant failure, and second malignancies as first events. Results Median follow-up was 52 months median for survivors. The 5-year cumulative incidence of competing mortality was 19.6% (95% CI, 15.8 to 23.4). On multivariable analysis, competing mortality was associated with female sex (hazard ratio [HR], 1.72; 95% CI, 1.13 to 2.63), increasing age (HR, 1.30; 95% CI, 1.04 to 1.62), increasing Charlson Comorbidity Index (HR, 1.24; 95% CI, 1.05 to 1.47), decreasing body mass index (HR, 0.33; 95% CI, 0.13 to 0.84), and decreasing distance traveled to the treating center (HR, 0.65; 95% CI, 0.44 to 0.98). Patients with zero, one, two, and > or = three risk factors had 5-year competing mortality of 8.9% (95% CI, 3.0% to 14.8%), 12.4% (95% CI, 7.0% to 17.8%), 22.1% (95% CI, 14.5% to 29.7%), and 39.3% (95% CI, 28.6% to 50.1%), respectively. CONCLUSION Competing mortality in advanced head and neck cancer is associated with several demographic and health status characteristics. Analyses of risk factors for competing mortality may be useful in outcomes reporting and designing clinical trials.
Promoter methylation of E-cadherin gene in gastric mucosa associated with Helicobacter pylori infection and in gastric cancer
Authors: A O-O Chan
Journal: Gut (2003)

<b>Background:</b><i>E-cadherin</i> is an adhesion molecule involved in tumour invasion/metastasis. Silencing of <i>E-cadherin</i> by promoter CpG methylation has been shown in both familial and sporadic gastric cancers. <i>Helicobacter pylori</i> is a class I carcinogen in gastric cancer. <b>Aims:</b> This study was undertaken to investigate the association between methylation of <i>E-cadherin</i> and <i>H pylori</i> in gastric mucosa from dyspeptic patients, and in intestinal metaplasia and primary and metastatic adenocarcinoma from surgical specimens of patients with gastric cancer. <b>Methods:</b><i>E-cadherin</i> methylation was studied using methylation specific polymerase chain reaction in microdissected tissue from biopsies or surgical resection specimens. <i>E-cadherin</i> expression was studied by immunohistochemistry. <b>Results:</b><i>E-cadherin</i> methylation was present in 31% (11/35) of gastric mucosae from dyspeptic patients, and was associated with <i>H pylori</i> infection (p=0.002), but was independent of the age of the patient or presence or absence of gastritis. <i>E-cadherin</i> methylation was present in 0% (0/8) of normal mucosa, 57% (12/21) of intestinal metaplasias, and 58% (15/26) of primary and 65% (21/32) of metastatic cancers. <i>E-cadherin</i> methylation status was concordant in 92% (11/12) of intestinal metaplasias and primary cancers, and in 85% (17/20) of primary and metastatic cancers from the same resected specimen. <i>E-cadherin</i> methylation in gastric cancer was associated with depth of tumour invasion (p=0.02) and regional nodal metastasis (p=0.05). <b>Conclusion:</b><i>E-cadherin</i> methylation is an early event in gastric carcinogenesis, and is initiated by <i>H pylori</i> infection.
Excess Dosing of Antiplatelet and Antithrombin Agents in the Treatment of Non–ST-Segment Elevation Acute Coronary Syndromes
Authors: Karen P. Alexander
Journal: JAMA (2005)

Effective medical care assumes delivery of evidence-based medicines to appropriate patients with doses comparable to those studied.To investigate dosing of unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and glycoprotein IIb/IIIa inhibitors, and the association between dosing and major outcomes.A prospective observational analysis in 387 US academic and nonacademic hospitals of 30,136 patients from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines) National Quality Improvement Initiative Registry who had non-ST-segment elevation acute coronary syndromes (NSTE ACS) with chest pain and either positive electrocardiograms or cardiac biomarkers between January 1 and September 30, 2004.Excessive dosing of UFH, LMWH, and glycoprotein IIb/IIIa inhibitors and major clinical outcomes, including bleeding, in-hospital mortality, and length of stay.A total of 3354 patients (42%) with NSTE ACS who were administered antithrombotic agents received at least 1 initial dose outside the recommended range. An excess dose was administered to 2934 patients (32.8%) treated with UFH, 1378 (13.8%) treated with LMWH, and 2784 (26.8%) treated with glycoprotein IIb/IIIa inhibitors. Factors associated with excess dosing included older age, as well as female sex, renal insufficiency, low body weight, diabetes mellitus, and congestive heart failure. Relative to those patients not administered excess dosages, patients with excess dosages of UFH, LMWH, and glycoprotein IIb/IIIa inhibitors either tended toward or had higher risks for major bleeding (adjusted odds ratio [OR], 1.08; 95% confidence interval [CI], 0.94-1.26; OR, 1.39; 95% CI, 1.11-1.74; and OR, 1.36; 95% CI, 1.10-1.68; respectively). Bleeding increased relative to the degree of excess dose and to the number of agents administered in excess (6.6% [237/3590] if neither heparin nor glycoprotein IIb/IIIa excess vs 22.2% [93/419] if both excess). Mortality and length of stay were also higher among those patients administered excess dosing. We estimated that 15% (400/2766) of major bleeding in this population may be attributable to excess dosing.Patients with NSTE ACS treated in the community often receive excess doses of antithrombotic therapy. Dosing errors occur more often in vulnerable populations and predict an increased risk of major bleeding.
Treatment of Acute Granulocytic Leukemias
Authors: J Bernard, M Weil, C I Jacquillat
Journal: Annual Review of Medicine (1974)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
CPAP and measures of cardiovascular risk in males with OSAS
Authors: M. Kohler, J. C. T. Pepperell, B. Casadei, S. Craig, N. Crosthwaite, J. R. Stradling, R. J. O. Davies
Journal: European Respiratory Journal (2008)

Overnight tape recordings of breathing movements, airflow, and arterial oxygen saturation from six infants aged 3 weeks to 7 months, who had cyanotic episodes associated with pertussis, were compared with recordings from 12 age matched healthy controls. In all patients clinically apparent apnoeic episodes were associated with the rapid onset and progression of central cyanosis. When overnight recordings were compared, patients with pertussis had a greater frequency of apnoeic pauses (particularly those greater than or equal to 12.0 seconds duration) and a greater frequency of episodes of hypoxaemia (oxygen saturation less than or equal to 80% for greater than or equal to 0.5 seconds) associated with apnoeic pauses. In addition to episodes of hypoxaemia associated with a prolonged absence of breathing movements, patients with pertussis had frequent dips in oxygen saturation in association with continued breathing movements with and without continued inspiratory airflow. These episodes of hypoxaemia during continued breathing movements were more common in patients with pertussis. These findings suggest that episodes of abnormal apnoea accompanied by evidence of a mismatch between ventilation and perfusion of the lungs may produce the rapid onset of severe hypoxaemia in infants with pertussis.
Pharmacological Intervention for Prevention of Left Ventricular Remodeling and Improving Prognosis in Myocardial Infarction
Authors: Hideki Ishii, Tetsuya Amano, Tatsuaki Matsubara, Toyoaki Murohara
Journal: Circulation (2008)

E arly reperfusion of totally occluded coronary arteries with thrombolysis and/or percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) reduces infarct size, cardiac mortality, and in-hospital events. 1,2rompt reperfusion of epicardial blood flow reduces infarct size and mortality rates, in-hospital events, and reinfarction.Furthermore, successful reperfusion greatly affects the reduction in infarct size and left ventricular (LV) function.The reduction in infarct size and the improvement in LV ejection fraction may decrease mechanical stress on the noninfarcted myocardium, preventing LV remodeling, including changes in LV size and shape. 3Preventing LV remodeling is of key importance after AMI because it may be related to a reduction in adverse cardiac events, including exacerbation of congestive heart failure and cardiac mortality rates. 4 -7 Although reperfusion therapy relieves and reduces ischemia and necrosis, the process of restoring coronary blood flow causes ischemiareperfusion injury in the ischemic myocardium, which limits the beneficial effects of reperfusion and may contribute to mortality despite successful reperfusion therapy. 8,9eperfusion injury is triggered by cellular and mitochondrial calcium overload, oxidant stress, endothelial dysfunction, reduction in nitric oxide production, and other factors.Because reperfusion injury limits the efficacy of reperfusion therapy alone, combined use with pharmacological intervention may moderate microcirculatory impairment and clinical outcomes.Such treatments may eventually reduce infarction size and prevent ischemic LV remodeling after AMI.Furthermore, medication in the chronic phase may affect LV remodeling and clinical prognoses.We undertook a systematic review of the literature based on pharmacological reductions in infarct size and prevention of LV remodeling, both of which may be associated with improved clinical outcomes, in cases of MI.In this review, searches through MEDLINE, LILACS, and SCIELO were the sources of information.
Transcriptional Profile of Mechanically Induced Genes in Human Vascular Smooth Muscle Cells
Authors: Yajun Feng, Jeong-Hee Yang, Hayden Huang, Scott P. Kennedy, Thomas G. Turi, John F. Thompson, Peter Libby, Richard T. Lee
Journal: Circulation Research (1999)

Abstract —Vascular smooth muscle cells must monitor and respond to their mechanical environment; however, the molecular response of these cells to mechanical stimuli remains incompletely defined. By applying a highly uniform biaxial cyclic strain to cultured cells, we used DNA microarray technology to describe the transcriptional profile of mechanically induced genes in human aortic smooth muscle cells. We first identified vascular endothelial growth factor (VEGF) as a mechanically induced gene in these cells; VEGF served as a positive control for these experiments. We then used a DNA microarray with 5000 genes with putative functions to identify additional mechanically induced genes. Surprisingly, relatively few genes are mechanically induced in human aortic smooth muscle cells. Only 3 transcripts of 5000 were induced &gt;2.5-fold: cyclooxygenase-1, tenascin-C, and plasminogen activator inhibitor-1. Downregulated transcripts included matrix metalloproteinase-1 and thrombomodulin. The transcriptional profile of mechanically induced genes in human aortic smooth muscle cells suggests a response of defense against excessive deformation. These data also demonstrate that in addition to identifying large clusters of genes that respond to a given stimulus, DNA microarray technology may be used to identify a small subset of genes that comprise a highly specific molecular response.
Impact of Dosage Frequency on Patient Compliance
Authors: Arsenio H P Paes, Albert Bakker, Carmen J Soe-Agnie
Journal: Diabetes Care (1997)

OBJECTIVE To evaluate the impact of dosage frequency on the compliance of patients who receive their medicines from community pharmacies. RESEARCH DESIGN AND METHODS Each month, patients received a supply of their medication in a Medication Event Monitoring Systems container, which registered each opening of the package. At the end of the study, the patients received a short questionnaire. The subjects were 91 diabetic patients using oral antidiabetic agents. Patients taking insulin and those who were unable to collect their medicines from the pharmacy were excluded from the study. Compliance was defined as the percentage of doses taken during the observation period. Another parameter used was compliance with the prescribed regimen, defined as the percentage of days in which the number of tablets were taken as prescribed. As a last parameter, compliance with the prescribed dose intervals was used. RESULTS Compliance is influenced by the frequency of doses. The compliance for this group of patients is 74.8%, with an average of 79% in the case of a dose once daily and 38% in the case of a dose three times daily. The predominant type of noncompliance in all groups was dose omissions. However, more than one-third of the patients used more doses than prescribed. Overconsumption is a frequently made mistake by patients on a one-dose daily schedule. CONCLUSIONS The reduction of dose frequency may decrease total noncompliance, but at the same time, it increases the risk of overconsumption. Reducing the frequency does not automatically result in a better therapeutic schedule. The choice of once or twice daily should depend on the therapeutic range of the drug.
Genetic modifiers of hypertension in soluble guanylate cyclase α1–deficient mice
Authors: Emmanuel S. Buys, Michael J. Raher, Andrew Kirby, Shahid Mohd, David M. Baron, Sarah R. Hayton, Laurel T. Tainsh, Patrick Y. Sips, Kristen M. Rauwerdink, Qingshang Yan, Robert E.T. Tainsh, Hannah R. Shakartzi, Christine Stevens, Kelly Decaluwé, Maria da Gloria Rodrigues-Machado, Rajeev Malhotra, Johan Van de Voorde, Tong Wang, Peter Brouckaert, Mark J. Daly, Kenneth D. Bloch
Journal: Journal of Clinical Investigation (2012)

Nitric oxide (NO) plays an essential role in regulating hypertension and blood flow by inducing relaxation of vascular smooth muscle. Male mice deficient in a NO receptor component, the α1 subunit of soluble guanylate cyclase (sGCα1), are prone to hypertension in some, but not all, mouse strains, suggesting that additional genetic factors contribute to the onset of hypertension. Using linkage analyses, we discovered a quantitative trait locus (QTL) on chromosome 1 that was linked to mean arterial pressure (MAP) in the context of sGCα1 deficiency. This region is syntenic with previously identified blood pressure-related QTLs in the human and rat genome and contains the genes coding for renin. Hypertension was associated with increased activity of the renin-angiotensin-aldosterone system (RAAS). Further, we found that RAAS inhibition normalized MAP and improved endothelium-dependent vasorelaxation in sGCα1-deficient mice. These data identify the RAAS as a blood pressure-modifying mechanism in a setting of impaired NO/cGMP signaling.
Acute myelocytic leukemia manifested by prominent generalized lymphadenopathy: Report of two cases with immunological, ultrastructural, and cytochemical studies
Authors: Diane D. Davey, Kathy Foucar, C. Patrick Burns, James A. Goeken
Journal: American Journal of Hematology (1986)

Abstract Although it is well recognized that granulocytic sarcoma can cause localized lymphadenopathy, widespread nodal involvement by acute myelocytic leukemia (AML), clinically mimicking non‐Hodgkin's lymphoma, has only been previously described twice. We report the clinicopathological, immunological, and cytochemical features of two patients who had widespread, prominent lymphadenopathy secondary to AML as well as concurrent marrow leukemia (M1 and M2). For one patient the lymphadenopathy was the predominant abnormality prompting him to seek medical attention, while the second patient had symptoms of infection following a 9‐month history of myelodysplasia. The disease in both patients was aggressive; one patient survived only 1 week and the other survived only 5 weeks after diagnosis. In both cases the granulocytic sarcoma was confirmed by cytochemistry studies (naphthol ASD‐chloroacetate esterase on tissue sections and myeloperoxidase on imprint smears), and electron microscopy, including morphology (both cases) or ultrastructural localization of myeloperoxidase (case 2). Non‐specific esterase activity was not detected in either patient's blasts, although serum lysozyme was elevated in both cases. Immunological studies revealed reactivity of both patients' cells with panleukocyte, MY4, MY7, OKM‐1, and Leu‐M1 monoclonal antibodies and with alpha‐1‐antitrypsin and muramidase antibodies. The cells of one of these patients also reacted wtih anti‐S‐100 protein. Although the cytochemical studies indicated that both cases exhibited only myeloid differentiation, the immunological markers suggested that the tumor cells possessed some features of monocytes, perhaps explaining their propensity for widespread tumor formation. Morphological, immunological, cytochemical, and ultrastructural methods of diagnosing granulocytic sarcoma are presented.
Ras/Erk Signaling Is Essential for Activation of Protein Synthesis by Gq Protein-Coupled Receptor Agonists in Adult Cardiomyocytes
Authors: Lijun Wang, Christopher G. Proud
Journal: Circulation Research (2002)

The Gq protein-coupled receptor agonists phenylephrine (PE) and endothelin-1 (ET-1) induce cardiac hypertrophy and stimulate protein synthesis in cardiomyocytes. This study aims to investigate how they activate mRNA translation in adult cardiomyocytes. PE and ET-1 do not activate protein kinase B but stimulate Ras and Erk, and their ability to activate protein synthesis was blocked by inhibition of Ras or MEK and by rapamycin, which inhibits mTOR (mammalian target of rapamycin). These agonists activated ribosomal protein S6 kinase 1 (S6K1) and induced phosphorylation of eIF4E-binding protein-1 (4E-BP1) and its release from eIF4E. These effects were blocked by inhibitors of MEK. Furthermore, adenovirus-mediated expression of constitutively-active MEK1 caused activation of S6K1, phosphorylation of 4E-BP1, and activation of protein synthesis in a rapamycin-sensitive manner. Expression of N17Ras inhibited the regulation of S6K1 and protein synthesis by GqPCR agonists. These data point to a signaling pathway involving Ras and MEK that acts, with mTOR, to control regulatory translation factors and activate protein synthesis. This study provides new insights into the mechanisms underlying the stimulation of protein synthesis by hypertrophic agents in heart.
Reproducibility of exhaled nitric oxide measurements in healthy and asthmatic adults and children
Authors: S.A. Kharitonov, F. Gonio, C. Kelly, S. Meah, P.J. Barnes
Journal: European Respiratory Journal (2003)

Airway inflammation in asthma is not measured routinely in clinical practice. Fractional exhaled nitric oxide (FE(NO)), a marker of airway inflammation, is increasingly used as an outcome measure in asthma intervention studies and yet the reproducibility of FE(NO) measurements is unknown. The reproducibility, day-to-day, diurnal variation and perception of standardised FE(NO) measurements were examined in 59 subjects (40 children aged 7-13 yrs and 19 adults aged 18-60 yrs), both healthy (n=30) and with mild (n = 29) asthma. FE(NO) was measured on five consecutive days (four measurements on the same day) for adults and twice on the same day for children. The coefficient of reproducibility expressed as the mean pooled standard deviation (n = 59, 675 estimations) was 2.11 parts per billion (ppb) and intraclass correlation coefficient was 0.99 in both children and adults. FE(NO) was significantly higher in asthma subjects (32.3 ppb) than in healthy subjects (16.3 ppb). There was no diurnal or day-to-day variation, or a learning effect, as the result of FE(NO) measurements were identical at results of the beginning and at the end of the study. It was concluded that fractional exhaled nitric oxide measurements are simple, reproducible, free from diurnal and day-to-day variation, and acceptable by both healthy and asthmatic adults and children, as a part of their routine visit to a physician.
THE SWINE LUNGWORM AS A RESERVOIR AND INTERMEDIATE HOST FOR HOG CHOLERA VIRUS
Authors: Richard E. Shope
Journal: The Journal of Experimental Medicine (1958)

Evidence that the swine lungworm can serve as reservoir and intermediate host for the hog cholera virus has been presented. The virus, however, is ordinarily carried in a masked form and must be provoked to pathogenicity by some stress before it can cause apparent disease. In the present experiments, ascaris larvae supplied the provocation needed to induce hog cholera in swine carrying lungworms infected with masked hog cholera virus. Provocation of the masked virus by ascaris larvae was seasonal in that it was effective only during a period embracing the first 5 months of the year.