tbuckley/cabot-search huggingface dataset:
Peak flow variation in childhood asthma: correlation with symptoms, airways obstruction, and hyperresponsiveness during long term treatment with inhaled corticosteroids
Authors: P. L P Brand, E. J Duiverman, H. J Waalkens, E. E M van Essen-Zandvliet, K. F Kerrebijn, None the Dutch CNSLD Study Group
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Guidelines for asthma management focus on treatment with inhaled corticosteroids and on home recording of peak expiratory flow (PEF). The effect of maintenance treatment with inhaled corticosteroids on PEF variation and its relation to other parameters of disease activity were examined in 102 asthmatic children aged 7–14 years. <h3>METHODS</h3> During 20 months of treatment with inhaled salbutamol, with or without inhaled budesonide (600 μg daily), forced expiratory volume in one second (FEV<sub>1</sub>), the dose of histamine required to provoke a fall in FEV<sub>1</sub> of more than 20% (PD<sub>20</sub>), the percentage of symptom free days, and PEF variation were assessed bimonthly. PEF variation was computed as the lowest PEF as a percentage of the highest PEF occurring over 14 days, the usual way of expressing PEF variation in asthma self-management plans. For each patient using inhaled corticosteroids within subject correlation coefficients (ρ) were computed of PEF variation to the percentage of symptom free days, FEV<sub>1</sub>, and PD<sub>20</sub>. <h3>RESULTS</h3> PEF variation decreased significantly during the first two months of treatment with inhaled corticosteroids and then remained stable. The same pattern was observed for symptoms and FEV<sub>1</sub>. In contrast, PD<sub>20</sub> histamine continued to improve throughout the whole follow up period. In individual patients predominantly positive associations of PEF variation with symptoms, FEV<sub>1</sub>, and PD<sub>20</sub> were found, but the ranges of these associations were wide. <h3>CONCLUSIONS</h3> During treatment with inhaled corticosteroids the changes in PEF variation over time show poor concordance with changes in other parameters of asthma severity. When only PEF is monitored, clinically relevant deteriorations in symptoms, FEV<sub>1</sub>, or PD<sub>20</sub> may be missed. This suggests that home recording of PEF alone may not be sufficient to monitor asthma severity reliably in children.
Lipoprotein Lipase Increases Lipoprotein Binding to the Artery Wall and Increases Endothelial Layer Permeability by Formation of Lipolysis Products
Authors: John C. Rutledge, Mable M. Woo, Allen A. Rezai, Linda K. Curtiss, Ira J. Goldberg
Journal: Circulation Research (1997)

Abstract Mechanisms responsible for the accumulation of low-density lipoprotein (LDL) were investigated in a new model, the perfused hamster aorta. To do this, we developed a method to study LDL flux in real time in individually perfused arteries; each artery served as its own control. Using quantitative fluorescence microscopy, the rates of LDL accumulation and efflux were separately determined. Perfusion of arteries with buffer plus lipoprotein lipase (LpL) increased LDL accumulation 5-fold (0.1±0.03 mV/min [control] versus 0.5±0.05 mV/min [LpL]) by increasing LDL retention in the artery wall. This effect was blocked by heparin and monoclonal antibodies directed against the amino-terminal region of apolipoprotein B (apo B). This suggests that specific regions of apo B are involved in LDL accumulation within arteries. Also, the effect of hydrolysis of triglyceride-rich lipoproteins on endothelial barrier function was studied. We compared endothelial layer permeability using a water-soluble reference molecule, fluorescently labeled dextran. When LpL was added to hypertriglyceridemic plasma, dextran accumulation within the artery wall increased &gt;4-fold (0.024±0.01 mV/min [control] versus 0.098±0.05 mV/min [LpL]). Under the same conditions, LpL increased LDL accumulation ≈3-fold (0.016±0.003 mV/min [control] versus 0.047±0.013 mV/min [LpL]). Rapid efflux of LDL from the artery wall indicated that increased endothelial layer permeability was the primary mechanism during periods of increased lipolysis. Our data demonstrate two LpL-mediated effects that may increase the amount of LDL in the artery wall. These findings may pertain to the observed relationship between increased postprandial lipemia and atherosclerosis.
The influence of diastolic and systolic function on exercise performance in heart failure due to dilated cardiomyopathy or ischemic heart disease
Authors: Mauro Pepi, PierGiuseppe Agostoni, GianCarlo Marenzi, Elisabetta Doria, Marco Guazzi, Gianfranco Lauri, Anna Maltagliati, Maurizio Guazzi
Journal: European Journal of Heart Failure (1999)
Heterozygous signal transducer and activator of transcription 3 mutations in hyper-IgE syndrome result in altered B-cell maturation
Authors: Almut Meyer-Bahlburg, Ellen D. Renner, Stacey Rylaarsdam, Janine Reichenbach, Lena F. Schimke, Amy Marks, Haig Tcheurekdjian, Robert Hostoffer, Archana Brahmandam, Troy R. Torgerson, Bernd H. Belohradsky, David J. Rawlings, Hans D. Ochs
Journal: Journal of Allergy and Clinical Immunology (2011)
Alarming levels of drug-resistant tuberculosis in Belarus: results of a survey in Minsk
Authors: Alena Skrahina, Henadz Hurevich, Aksana Zalutskaya, Evgeni Sahalchyk, Andrei Astrauko, Wayne van Gemert, Sven Hoffner, Valiantsin Rusovich, Matteo Zignol
Journal: European Respiratory Journal (2011)

Resistance to anti-tuberculosis (TB) medicines is a major public health threat in most countries of the former Soviet Union. As no representative and quality-assured information on the magnitude of this problem existed in Belarus, a survey was conducted in the capital city of Minsk. Between November 2009 and December 2010, 156 consecutively diagnosed new and 68 previously treated culture-positive TB patients residing in Minsk were enrolled in the survey. Mycobacterium tuberculosis isolates were obtained from each patient and tested for susceptibility to first- and second-line anti-TB drugs. Multidrug-resistant (MDR)-TB was found in 35.3% (95% CI 27.7-42.8) of new patients and 76.5% (95% CI 66.1-86.8) of those previously treated. Overall, nearly one in two patients enrolled had MDR-TB. Extensively drug-resistant TB was reported in 15 of the 107 MDR-TB patients (14.0%, 95% CI 7.3-20.7). Patients <35 yrs of age have shown a two times higher odds ratio of multidrug-resistant TB than those aged >35 yrs. The findings of this survey in Minsk city are alarming and represent the highest proportions of MDR-TB ever recorded in the world. This study greatly contributes to the understanding of the burden of drug-resistant TB in urban areas of Belarus.
Diet-Quality Scores and the Risk of Type 2 Diabetes in Men
Authors: Lawrence de Koning, Stephanie E. Chiuve, Teresa T. Fung, Walter C. Willett, Eric B. Rimm, Frank B. Hu
Journal: Diabetes Care (2011)

To 1) compare associations of diet-quality scores, which were inversely associated with cardiovascular disease, with incident type 2 diabetes and 2) test for differences in absolute-risk reduction across various strata.Men from the Health Professionals Follow-Up Study, who were initially free of type 2 diabetes, cardiovascular disease, or cancer (n = 41,615), were followed for ≤ 20 years. The Healthy Eating Index (HEI) 2005, the alternative HEI (aHEI) the Recommended Food Score, the alternative Mediterranean Diet (aMED) Score, and the Dietary Approaches to Stop Hypertension (DASH) Score were calculated from food-frequency questionnaires. Cox proportional hazard models with time-varying covariates were used to assess risk by quintiles and continuous intervals.There were 2,795 incident cases of type 2 diabetes. After multivariate adjustment, the aHEI, aMED, and DASH scores were significantly associated with reduced risk. A 1-SD increase was associated with 9-13% reduced risk (P < 0.01), and the DASH score was associated with lower risk independent of other scores. These scores were associated with lower absolute risk among those who were overweight or obese compared with normal weight (P for interaction < 0.01).Several diet-quality scores were associated with a lower risk of type 2 diabetes and reflect a common dietary pattern characterized by high intakes of plant-based foods such as whole grains; moderate alcohol; and low intakes of red and processed meat, sodium, sugar-sweetened beverages, and trans fat. High-quality diets may yield the greatest reduction in diabetes cases when followed by those with a high BMI.
Variability and Sample Size Requirements of Quality-of-Life Measures: A Randomized Study of Three Major Questionnaires
Authors: Yin-Bun Cheung, Cynthia Goh, Julian Thumboo, Kei-Siong Khoo, Joseph Wee
Journal: Journal of Clinical Oncology (2005)

To compare the variability and sample size requirements of the global quality-of-life (QOL) scores of the following three major QOL instruments: the Functional Assessment of Cancer Therapy-General (FACT-G), Functional Living Index-Cancer (FLIC), and European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 (EORTC QLQ-C30).Cancer patients were randomly assigned to answer two of the three instruments using an incomplete block design (n = 1,268). The instruments were compared in terms of coefficient of variation, effect size in detecting a difference between patients with different performance status, and correlation coefficient between scores at baseline and follow-up.The FACT-G and FLIC had significantly smaller coefficients of variation than the EORTC QLQ-C30 (both P < .05). The FLIC also had significantly larger correlation coefficients between scores at baseline and follow-up than the EORTC QLQ-C30 (P < .05). The FACT-G and the FLIC had a larger effect size in a cross-sectional and longitudinal setting, respectively, than the EORTC QLQ-C30 in differentiating patients with different performance status (both P < .05).In some aspects, the FACT-G and FLIC global QOL scores had smaller variability and larger discriminative ability than the EORTC QLQ-C30. Further research using other criteria to compare the three instruments is recommended.
Targeting Sphingosine Kinase 1 Inhibits Akt Signaling, Induces Apoptosis, and Suppresses Growth of Human Glioblastoma Cells and Xenografts
Authors: Dmitri Kapitonov, Jeremy C. Allegood, Clint Mitchell, Nitai C. Hait, Jorge A. Almenara, Jeffrey K. Adams, Robert E. Zipkin, Paul Dent, Tomasz Kordula, Sheldon Milstien, Sarah Spiegel
Journal: Cancer Research (2009)

Abstract Sphingosine-1-phosphate is a potent sphingolipid mediator of diverse processes important for brain tumors, including cell growth, survival, migration, invasion, and angiogenesis. Sphingosine kinase 1 (SphK1), one of the two isoenzymes that produce sphingosine-1-phosphate, is up-regulated in glioblastoma and has been linked to poor prognosis in patients with glioblastoma multiforme (GBM). In the present study, we found that a potent isotype-specific SphK1 inhibitor, SK1-I, suppressed growth of LN229 and U373 glioblastoma cell lines and nonestablished human GBM6 cells. SK1-I also enhanced GBM cell death and inhibited their migration and invasion. SK1-I rapidly reduced phosphorylation of Akt but had no significant effect on activation of extracellular signal-regulated kinase 1/2, another important survival pathway for GBM. Inhibition of the concomitant activation of the c-Jun-NH2-kinase pathway induced by SK1-I attenuated death of GBM cells. Importantly, SK1-I markedly reduced the tumor growth rate of glioblastoma xenografts, inducing apoptosis and reducing tumor vascularization, and enhanced the survival of mice harboring LN229 intracranial tumors. Our results support the notion that SphK1 may be an important factor in GBM and suggest that an isozyme-specific inhibitor of SphK1 deserves consideration as a new therapeutic agent for this disease. [Cancer Res 2009;69(17):6915–23]
Dissociation of Regional Adaptations to Ischemia and Global Myolysis in an Accelerated Swine Model of Chronic Hibernating Myocardium
Authors: Salome A. Thomas, James A. Fallavollita, Gen Suzuki, Marcel Borgers, John M. Canty
Journal: Circulation Research (2002)

We tested the hypothesis that an acute critical limitation in coronary flow reserve could rapidly recapitulate the physiological, molecular, and morphological phenotype of hibernating myocardium. Chronically instrumented swine were subjected to a partial occlusion to produce acute stunning, followed by reperfusion through a critical stenosis. Stenosis severity was adjusted serially so that hyperemic flow was severely reduced yet always higher than the preocclusion resting level. After 24 hours, resting left anterior descending coronary artery (LAD) wall thickening had decreased from 36.3±4.0% to 25.5±3.7% ( P &lt;0.05), whereas resting flow had remained normal (67±6 versus 67±8 mL/min, respectively). Although peak hyperemic flow exceeded the prestenotic value, resting flow (45±10 mL/min) and LAD wall thickening (17.0±5.0%) progressively decreased after 2 weeks, when physiological features of hibernating myocardium had developed. Regional reductions in sarcoplasmic reticulum proteins were present in hibernating myocardium but absent in stunned myocardium evaluated after 24 hours. Histological analysis showed an increase in connective tissue along with myolysis (myofibrillar loss per myocyte &gt;10%) and increased glycogen typical of hibernating myocardium in the LAD region (33±3% of myocytes from animals with hibernating myocardium versus 15±4% of myocytes from sham-instrumented animals, P &lt;0.05). Surprisingly, the frequency of myolysis was similar in normally perfused remote regions from animals with hibernating myocardium (32±7%). We conclude that the regional physiological and molecular characteristics of hibernating myocardium develop rapidly after a critical limitation in flow reserve. In contrast, the global nature of myolysis and increased glycogen content dissociate them from the intrinsic adaptations to ischemia. These may be related to chronic elevations in preload but appear unlikely to contribute to chronic contractile dysfunction.
Hemoglobin A1c as a Diagnostic Tool for Diabetes Screening and New-Onset Diabetes Prediction
Authors: Sung Hee Choi, Tae Hyuk Kim, Soo Lim, Kyong Soo Park, Hak C. Jang, Nam H. Cho
Journal: Diabetes Care (2011)

Various cutoff levels of hemoglobin A(1c) (A1C) have been suggested to screen for diabetes, although more consensus about the best level, especially for different ethnicities, is required. We evaluated the usefulness of A1C levels when screening for undiagnosed diabetes and as a predictor of 6-year incident diabetes in a prospective, population-based cohort study.A total 10,038 participants were recruited from the Ansung-Ansan cohort study. All subjects underwent a 75-g oral glucose tolerance test at baseline and at each biennial follow-up. Excluding subjects with a previous history of diabetes (n = 572), the receiver operating characteristic curve was used to evaluate the diagnostic accuracy of the A1C cutoff. The Cox proportional hazards model was used to predict diabetes at 6 years.At baseline, 635 participants (6.8%) had previously undiagnosed diabetes. An A1C cutoff of 5.9% produced the highest sum of sensitivity (68%) and specificity (91%). At 6 years, 895 (10.2%) subjects had developed incident diabetes. An A1C cutoff of 5.6% had the highest sum of sensitivity (59%) and specificity (77%) for the identification of subsequent 6-year incident diabetes. After multivariate adjustment, men with baseline A1C ≥5.6% had a 2.4-fold increased risk and women had a 3.1-fold increased risk of new-onset diabetes.A1C is an effective and convenient method for diabetes screening. An A1C cutoff of 5.9% may identify subjects with undiagnosed diabetes. Individuals with A1C ≥5.6% have an increased risk for future diabetes.
Peak flow diaries in childhood asthma are unreliable
Authors: A W A Kamps, R J Roorda, P L P Brand
Journal: Thorax (2001)

<h3>BACKGROUND</h3> A study was undertaken to investigate the compliance with and accuracy of peak flow diaries in childhood asthma. <h3>METHODS</h3> Forty asthmatic children (5–16 years) were asked to perform peak flow measurements twice daily for 4 weeks by means of an electronic peak flow meter and to record values in a written diary. Patients and parents were unaware that the device stored the peak flow values on a microchip. In random order, half of the patients were only told that the device allowed for more accurate assessment of peak flow while the other half were told that accurate recording of peak flow was important because the results would be used in guiding adjustments to treatment. Data in the written diary (reported data) were compared with those from the electronic diary (actual data). <h3>RESULTS</h3> In the entire study population the mean (SD) actual compliance (77.1 (20.5)%) was much lower than the mean reported compliance (95.7 (9.1)%) (95% CI for difference 12.7% to 24.4%) The percentage of correct peak flow entries decreased from 56% to &lt;50% from the first to the last study week (p&lt;0.04), mainly as a result of an increase in self-invented peak flow entries. Results were comparable for both groups. For incorrect peak flow entries the mean difference between written and electronically recorded entries ranged from –72 to 34 l/min per patient. <h3>CONCLUSIONS</h3> Peak flow diaries kept by asthmatic children are unreliable. Electronic peak flow meters should be used if peak flow monitoring is required in children with asthma.
Drug Delivery with Carbon Nanotubes for <i>In vivo</i> Cancer Treatment
Authors: Zhuang Liu, Kai Chen, Corrine Davis, Sarah Sherlock, Qizhen Cao, Xiaoyuan Chen, Hongjie Dai
Journal: Cancer Research (2008)

Abstract Chemically functionalized single-walled carbon nanotubes (SWNT) have shown promise in tumor-targeted accumulation in mice and exhibit biocompatibility, excretion, and little toxicity. Here, we show in vivo SWNT drug delivery for tumor suppression in mice. We conjugate paclitaxel (PTX), a widely used cancer chemotherapy drug, to branched polyethylene glycol chains on SWNTs via a cleavable ester bond to obtain a water-soluble SWNT-PTX conjugate. SWNT-PTX affords higher efficacy in suppressing tumor growth than clinical Taxol in a murine 4T1 breast cancer model, owing to prolonged blood circulation and 10-fold higher tumor PTX uptake by SWNT delivery likely through enhanced permeability and retention. Drug molecules carried into the reticuloendothelial system are released from SWNTs and excreted via biliary pathway without causing obvious toxic effects to normal organs. Thus, nanotube drug delivery is promising for high treatment efficacy and minimum side effects for future cancer therapy with low drug doses. [Cancer Res 2008;68(16):6652–60]
Effects of protriptyline on sleep related disturbances of breathing in restrictive chest wall disease.
Authors: A K Simonds, R A Parker, M A Branthwaite
Journal: Thorax (1986)

The effects of protriptyline on sleep stage distribution and gas exchange have been assessed in eight patients with nocturnal hypoventilation secondary to restrictive chest wall disease. At a dose of 10-20 mg taken when they retired the total sleeping time was unaltered but the proportion of rapid eye movement (REM) sleep fell from 22% to 12% (p less than 0.05). The total time spent at an arterial oxygen saturation of less than 80% decreased (p less than 0.01) and the magnitude of the fall correlated with the reduction in REM sleep (r = 0.67, p less than 0.05). There was also a reduction in the maximum carbon dioxide tension reached during the night (p less than 0.01). The arterial oxygen tension measured diurnally increased (p less than 0.05) from a median of 8.0 kPa (60 mm Hg) to 9.0 kPa (67.5 mm Hg), but the carbon dioxide tension and base excess were unchanged. Anticholinergic side effects were experienced by most patients but did not limit treatment.
Family History of Diabetes in Relation to Different Types of Obesity and Change of Obesity During 12-yr Period: Results from prospective population study of women in Göteborg, Sweden
Authors: Leif Lapidus, Calle Bengtsson, Lauren Lissner, Ulf Smith
Journal: Diabetes Care (1992)

OBJECTIVE--To assess the relationship between family history and different types of obesity and change in obesity in a longitudinal population study. RESEARCH DESIGN AND METHODS--A longitudinal population study of 1462 randomly selected women (38-60 yr old) was conducted in Göteborg, Sweden, in 1968-69. The women were restudied after 12 yr. RESULTS--A family history of diabetes in mothers but not fathers showed, in univariate analysis, a significant positive association with obesity expressed as BMI. A family history of diabetes in the mothers was inversely related to body fat distribution expressed as WHR. No other association was observed between family history of diabetes and WHR. The association with BMI was independent of age, WHR, smoking habits, blood glucose, systolic blood pressure, serum cholesterol, serum triglycerides, maternal obesity, and the incidence of diabetes during the 12-yr follow-up period. Twelve years later, in 1980-1981, an independent association still existed between family history for diabetes and BMI measured at that examination, whereas there was no relationship with WHR. Women who had a family history of diabetes increased their BMI significantly more during the 12-yr follow-up compared with the women without a family history of diabetes, whereas there was no difference for the change of WHR. Family history of coronary heart disease and family history of cancer did not correlate to any kind of obesity. CONCLUSIONS--These findings indicate that family history of diabetes is related to overall obesity but not to abdominal adiposity per se.
ERBB3-Independent Activation of the PI3K Pathway in EGFR-Mutant Lung Adenocarcinomas
Authors: Xiaoling Song, Pang-Dian Fan, Amlak Bantikassegn, Udayan Guha, David W. Threadgill, Harold Varmus, Katerina Politi
Journal: Cancer Research (2015)

ERBB3, a member of the EGFR family of receptor tyrosine kinases, has been implicated in activation of the PI3K pathway in human lung adenocarcinomas driven by EGFR mutations. We investigated the contribution of ERBB3 to the initiation, progression, and therapeutic response of EGFR-induced lung adenocarcinomas using tetracycline- and tamoxifen-inducible transgenic mouse models. Deletion of Erbb3 at the time of induction of mutant EGFR had no effect on tumorigenesis, demonstrating that ERBB3 is not required to initiate tumorigenesis. Tumors that developed in the absence of ERBB3 remained sensitive to EGFR tyrosine kinase inhibitors and retained activation of the PI3K-AKT pathway. Interestingly, acute loss of Erbb3 suppressed further growth of established EGFR(L858R)-mediated lung tumors. Four weeks after deletion of Erbb3, the tumors exhibited phosphorylation of EGFR, of the adaptor proteins GAB1 and GAB2, and of the downstream signaling molecules AKT and ERK, suggesting that alternative signaling pathways could compensate for loss of Erbb3. Similar to our observations with mouse tumors, we found that GAB adaptor proteins play a role in ERBB3-independent activation of the PI3K pathway by mutant EGFR in EGFR-mutant human cell lines. Finally, in such cell lines, increased levels of phosphorylation of ERBB2 or MET were associated with reduced sensitivity to acute loss of ERBB3, suggesting remarkable plasticity in the signaling pathways regulated by mutant EGFR with important therapeutic implications.