tbuckley/cabot-search huggingface dataset:
Comparison of short courses of oral prednisolone and fluticasone propionate in the treatment of adults with acute exacerbations of asthma in primary care.
Authors: M L Levy, C Stevenson, T Maslen
Journal: Thorax (1996)

BACKGROUND: Oral corticosteroids used in short courses for acute asthma are regarded as safe, although the frequent use of these drugs may result in patients suffering from systemic side effects. It has become common practice for patients to increase their own inhaled corticosteroid intake when their asthma goes out of control, but it has never been established whether a high dose of inhaled corticosteroid can be as effective as a short course of oral corticosteroid in the treatment of acute exacerbations. METHODS: A multicentre, randomised, double blind, double dummy, parallel group study was undertaken to determine whether the introduction of a high dose of inhaled fluticasone propionate (2 mg daily) is as effective as a short reducing course of oral prednisolone (starting at 40 mg/day and reducing by 5 mg every other day) in the treatment of acute exacerbations of asthma not considered severe enough for admission to hospital but requiring treatment with oral corticosteroid. RESULTS: Four hundred and thirteen adult asthmatic subjects who presented to their general practitioner with an acute exacerbation of asthma were recruited in 47 general practices in the United Kingdom. Treatment failures, defined as a reduction in peak expiratory flow (PEF) to below 60% of the patient9s best/predicted value on two consecutive occasions or persistent symptoms with no improvement on three consecutive days, occurred in 23% of patients who received oral prednisolone and 27% who received inhaled fluticasone propionate (difference in percentage of treatment failures 4.3, 95% CI -4.1 to 12.8, p = 0.31). In each group 48% were classified as treatment successes, defined as a 10% or greater increase in percentage best/predicted morning PEF. Both treatments were equally well tolerated. CONCLUSIONS: There is no evidence of a significant difference in efficacy between a reducing dose course of oral prednisolone and high dose inhaled fluticasone propionate in mild exacerbations of asthma which do not require admission to hospital.
Microscopic and macroscopic measurements of emphysema: relation to carbon monoxide gas transfer.
Authors: A McLean, P M Warren, M Gillooly, W MacNee, D Lamb
Journal: Thorax (1992)

BACKGROUND: Studies of the relation between the severity of structural change in emphysema and physiological abnormality have been based on macroscopic assessments, which have not been truly quantitative or sensitive enough to detect early changes. With a highly reproducible method for measuring emphysema using histological sections and a semiautomatic image analysis system, this quantitative assessment of emphysema was compared with a semiquantitative macroscopic assessment of emphysema and measurements of carbon monoxide gas transfer. METHODS: Microscopic and macroscopic measurements of emphysema on 44 thoracotomy specimens were compared; only two were from non-smokers. Airspace wall surface area per unit volume was measured microscopically with an automatic image analyser and expressed as both the mean airspace wall surface area per unit volume and the mean value of the five fields with the lowest values. Macroscopic emphysema was measured directly on a tracing of the midsagittal slice using a digitising tablet attached to a microcomputer and expressed as a percentage of the total area of lung. In cases with centriacinar emphysema the number of discrete lesions was counted. RESULTS: The area of macroscopic emphysema ranged from 0 to 78% of the total area of lung examined, but most patients had less than 1% involvement so that the distribution was highly skewed. Both mean airspace wall surface area per unit volume and the mean of five fields with the lowest airspace wall surface area per unit volume were normally distributed, with mean airspace areas ranging from 8.8 to 25.4 mm2/mm3 (mean 18.1 mm2/mm3). In lobes with centriacinar emphysema the number of discrete lesions correlated with airspace wall surface area per unit volume and with preoperative carbon monoxide transfer factor (TLCO) per unit lung volume. However, other measurements of macroscopic emphysema did not correlate with loss of alveolar wall surface area, and there was considerable overlap between subjects with no or minimal macroscopic emphysema and those with more severe disease. TLCO correlated with both mean airspace wall surface area per unit volume and the mean of five fields with the lowest airspace wall surface area per unit volume but not with the severity of macroscopic emphysema. CONCLUSION: If emphysema is to be quantified it must be measured microscopically; macroscopic measurements do not, in general, reflect the microscopic loss of airspace wall.
Insulin Degradation: Progress and Potential*
Authors: William C. Duckworth, Robert G. Bennett, Frederick G. Hamel
Journal: Endocrine Reviews (1998)

Insulin degradation is a regulated process that plays a role in controlling insulin action by removing and inactivating the hormone. Abnormalities in insulin clearance and degradation are present in various pathological conditions including type 2 diabetes and obesity and may be important in producing clinical problems. The uptake, processing, and degradation of insulin by cells is a complex process with multiple intracellular pathways. Most evidence supports IDE as the primary degradative mechanism, but other systems (PDI, lysosomes, and other enzymes) undoubtedly contribute to insulin metabolism. Recent studies support a multifunctional role for IDE, as an intracellular binding, regulatory, and degradative protein. IDE increases proteasome and steroid hormone receptor activity, and this activation is reversed by insulin. This raises the possibility of a direct intracellular interaction of insulin with IDE that could modulate protein and fat metabolism. The recent findings would place intracellular insulin-IDE interaction into the insulin signal transduction pathway for mediating the intermediate effects of insulin on fat and protein turnover.
THE ROLE OF ESSENTIAL FATTY ACIDS IN DEVELOPMENT
Authors: William C. Heird, Alexandre Lapillonne
Journal: Annual Review of Nutrition (2005)

The presence of docosahexaenoic acid (DHA) and arachidonic acid (ARA) in human milk but not in infant formula, coupled with lower plasma and brain lipid contents of DHA in formula-fed than in breast-fed infants and reports of higher IQ in individuals who were breast-fed versus formula-fed as infants, suggest that exogenous DHA (and ARA) may be essential for optimal development. Thus, since 1990, several studies have examined the impact of formulas containing DHA or DHA plus ARA on visual function and neurodevelopmental outcome. Some of these studies have shown benefits but others have not. These results leave largely unanswered the question of whether these fatty acids are beneficial for either the term or preterm infant. However, evidence that preterm infants might benefit is somewhat more convincing than that for term infants. Despite the limited evidence for efficacy, formulas supplemented with DHA and ARA are now available and appear to be safe.
Effects of Clinical Nutrition Education and Educator Discipline on Glycemic Control Outcomes in the Indian Health Service
Authors: Charlton Wilson, Tammy Brown, Kelly Acton, Susan Gilliland
Journal: Diabetes Care (2003)

OBJECTIVE—We used the Indian Health Service (IHS) Diabetes Care and Outcomes Audit to assess the effectiveness of clinical nutrition education in reducing HbA1c levels and to test the relative effectiveness of clinical nutrition education when it was delivered by a registered dietitian (RD) compared with an educator from another discipline (non-RD). RESEARCH DESIGN AND METHODS—We examined clinical care data collected by the IHS Diabetes Care and Outcomes Audit of 7,490 medical records during 2001. Glycemic control was assessed by using the difference between the two most recent HbA1c levels during 2001. Age, BMI, duration of diabetes, type of treatment, proteinuria, and facility were included as covariates. Clinical nutrition education was defined as documentation in the record of any diet instruction and educator discipline classified as RD or non-RD. ANCOVA methods were used to assess the effects of diet education and educator discipline on differences between the two HbA1c measurements and to adjust for differences in the distribution of covariates among the education groups. RESULTS—After adjustment for age, sex, type of treatment, duration of diabetes, BMI, initial HbA1c level, and clinical facility, clinical nutrition education and educator discipline were each associated with changes in HbA1c levels (P &amp;lt; 0.001). Those receiving clinical nutrition education from an RD or from an RD as well as a non-RD had the largest improvements in HbA1c levels (−0.26 and −0.32, respectively) compared with those receiving either only non-RD or no clinical nutrition education (−0.19 and −0.10, respectively). CONCLUSIONS—Clinical nutrition education in the IHS is associated with favorable trends in glycemic control. To be effective, clinical nutrition education should be delivered by an RD or a team that includes an RD.
Measurement precision: it does matter where you take the skinfolds
Authors: Michael J Marfell-Jones, Patria Hume
Journal: British Journal of Sports Medicine (2010)

Introduction For an assessment to have value, it must measure the parameter of interest and be reliable enough to detect small differences. To minimise TEM differences between repeat skinfold measures, measurement sites and measurement techniques have been defined by the International Society for the Advancement of Kinanthropometry (ISAK). The aim of this study, therefore, was to examine the significance of accurate skinfold measurement site location in order to confirm or relax the specific protocols that ISAK has defined. Methods Nine measurements, in a 1-cm grid pattern, centred on each of the eight ISAK-specified skinfold sites, were taken three times at each grid point by each of the two ISAK criteria (level 4) measurers using Harpenden skinfold callipers, on 12 healthy participants (11 males and 1 female; 27.1 ± 6.5 years; 177.3 ± 7.4 cm; 77.8 ± 12.7 kg). Results Skinfolds taken at the eight peripheral grid points were generally different (45 out of 64 = 70%) from the skinfolds taken at the central ISAK grid point. The effect was multidirectional. The subscapular was the most robust site in terms of least effect with deviation away from the central point. All other skinfold sites showed some variation with most care needed in marking the biceps and triceps sites. Discussion/conclusion Measuring 1 cm away from a defined ISAK site produced significant differences in the majority of skinfold measurement values obtained. No site was totally free from this variation. Therefore, adherence to identifying, marking and measuring at the defined site is essential.
1018 USEFULNESS OF GD-EOB-DTPA CONTRAST ENHANCED MRI IN THE DIAGNOSIS OF HEPATOCELLULAR CARCINOMA (HCC). APPLICABILITY IN LIVER CIRRHOSIS
Authors: M. Várela, M. Rodriguez-Peláez, R. Menéndez de Llano, V. Blanco-Lorenzo, A. Mesa-Álvarez, V. Cadahía-Rodrigo, M.L. González-Diéguez, L.H. Luyando, M. Rodríguez
Journal: Journal of Hepatology (2011)
Mortality in rheumatoid arthritis patients with disease onset in the 1980s
Authors: E. Lindqvist, K. Eberhardt
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVE</h3> Several previous studies have shown increased mortality in rheumatoid arthritis (RA) patients. This study investigated if this was true also for patients with disease onset in the 1980s. <h3>PATIENTS AND METHODS</h3> The study group comprised 183 patients (67 men and 116 women) with definite RA participating in an ongoing prospective study. Mean age at onset of disease was 51 years, and mean duration of joint symptoms at inclusion was 11 months. The patients were included between 1985–89. Seventy five per cent of the patients were rheumatoid factor (RF) positive, 85% carried the shared epitope, and 90% became erosive. By 1 September 1997 the number and causes of death, obtained from the death certificates, were recorded. Standardised mortality ratio (SMR) was calculated, comparing the observed number of deaths in the cohort with the expected number of deaths in the general population in the same area, age and sex matched. The predictive values of demographics, genotype, RF status, and clinical data at baseline were estimated using the Cox proportional hazards regression model. <h3>RESULTS</h3> Eighteen patients (11 men and 7 women) had died compared with 20 expected deaths. SMR with 95% confidence intervals was 87 (53, 136). There was no significant increase in the number of deaths at any time during follow up for either sex. RA was not the main cause of death in any of the cases. By reading the patient charts two cases were found where RA or its treatment could have contributed to death. No RA related variable contributed significantly to an increased risk of death. <h3>CONCLUSION</h3> There was no increased mortality during the first 8–13 years of disease in this group of patients who developed RA in the 1980s.
Challenging beliefs in sports nutrition: are two ‘core principles’ proving to be myths ripe for busting?
Authors: Peter Brukner
Journal: British Journal of Sports Medicine (2013)

Let's start with a couple of quiz questions. Put your hands up if you have given the following pieces of advice to your patients/athletes. (1) Thirst is not a good indicator of hydration. You must drink lots of fluids before, during and after exercise. (2) The optimum diet for weight control, general health and athletic performance consists of low fat, high carbohydrate.

Well, both my hands are up, and I suspect I am in good company among sports medicine professionals. For the past 30 years, these have been two of the basic tenets of sports nutrition. Recently, however, both these universally regarded ‘truths’ have been challenged.

We now know that excessive intake of fluid during endurance events can lead to exercise-associated hyponatraemic encephalopathy (EAHE) or ‘water intoxication’.1 There have been a number of deaths reported from this syndrome. One of the researchers who has been prominent in researching this topic is Professor Tim Noakes from the University of Cape Town. In his recent book ‘Waterlogged’,2 Noakes explains how drinking too much water can lead to fluid retention and EAHE in those who also have the syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Endurance athletes have been encouraged for the past three decades to not wait until they were thirsty, but to drink large amounts of water or sports drinks to prevent dehydration and heat illness. Noakes advises that excessive fluid overload is the major danger in endurance exercise, not …
Thrombospondin-1 Deficiency Accelerates Atherosclerotic Plaque Maturation in <i>ApoE</i> <sup>−/−</sup> Mice
Authors: Rute Moura, Marc Tjwa, Petra Vandervoort, Soetkin Van kerckhoven, Paul Holvoet, Marc F. Hoylaerts
Journal: Circulation Research (2008)

Thrombospondin (TSP)1 is implicated in various inflammatory processes, but its role in atherosclerotic plaque formation and progression is unclear. Therefore, the development of atherosclerosis was compared in ApoE −/− and Tsp1 −/− ApoE −/− mice kept on a normocholesterolemic diet. At 6 months, morphometric analysis of the aortic root of both mouse genotypes showed comparable lesion areas. Even when plaque burden increased ≈5-fold in ApoE −/− and 10-fold in Tsp1 −/− ApoE −/− mice, during the subsequent 3 months, total plaque areas were comparable at 9 months. In contrast, plaque composition differed substantially between genotypes: smooth muscle cell areas, mostly located in the fibrous cap of ApoE −/− plaques, both at 6 and 9 months, were 3-fold smaller in Tsp1 −/− ApoE −/− plaques, which, in addition, were also more fibrotic. Moreover, inflammation by macrophages was twice as high in Tsp1 −/− ApoE −/− plaques. This correlated with a 30-fold elevated incidence of elastic lamina degradation, with matrix metalloproteinase-9 accumulation, underneath plaques and manifestation of ectasia, exclusively in Tsp1 −/− ApoE −/− mice. At 9 months, the necrotic core was 1.4-fold larger and 4-fold higher numbers of undigested disintegrated apoptotic cells were found in Tsp1 −/− ApoE −/− plaques. Phagocytosis of platelets by cultured Tsp1 −/− macrophages revealed the instrumental role of TSP1 in phagocytosis, corroborating the defective intraplaque phagocytosis of apoptotic cells. Hence, the altered smooth muscle cell phenotype in Tsp1 −/− ApoE −/− mice has limited quantitative impact on atherosclerosis, but defective TSP1-mediated phagocytosis enhanced plaque necrotic core formation, accelerating inflammation and macrophage-induced elastin degradation by metalloproteinases, speeding up plaque maturation and vessel wall degeneration.
New Therapies for Stroke Prevention in Atrial Fibrillation
Authors: Jane E. Freedman, Bernard J. Gersh
Journal: Circulation (2009)

A trial fibrillation is the most frequent sustained arrhyth- mia seen in clinical practice, and the public health implications of this growing epidemic are sobering.Approximately 2.3 to 3.2 million people are currently affected in the United States; the risk of stroke ranges from 1% to 7% per year; and atrial fibrillation accounts for Ϸ45% of embolic strokes annually, which amounts to Ϸ100 000 strokes per year. 1,2Moreover, atrial fibrillation is an independent predictor of mortality in most studies.
A Diverse Array of Cancer-Associated <i>MTOR</i> Mutations Are Hyperactivating and Can Predict Rapamycin Sensitivity
Authors: Brian C. Grabiner, Valentina Nardi, Kıvanç Birsoy, Richard Possemato, Kuang Shen, Sumi Sinha, Alexander Jordan, Andrew H. Beck, David M. Sabatini
Journal: Cancer Discovery (2014)

Genes encoding components of the PI3K-AKT-mTOR signaling axis are frequently mutated in cancer, but few mutations have been characterized in MTOR, the gene encoding the mTOR kinase. Using publicly available tumor genome sequencing data, we generated a comprehensive catalog of mTOR pathway mutations in cancer, identifying 33 MTOR mutations that confer pathway hyperactivation. The mutations cluster in six distinct regions in the C-terminal half of mTOR and occur in multiple cancer types, with one cluster particularly prominent in kidney cancer. The activating mutations do not affect mTOR complex assembly, but a subset reduces binding to the mTOR inhibitor DEPTOR. mTOR complex 1 (mTORC1) signaling in cells expressing various activating mutations remains sensitive to pharmacologic mTOR inhibition, but is partially resistant to nutrient deprivation. Finally, cancer cell lines with hyperactivating MTOR mutations display heightened sensitivity to rapamycin both in culture and in vivo xenografts, suggesting that such mutations confer mTOR pathway dependency.
Electroporation-Based Technologies for Medicine: Principles, Applications, and Challenges
Authors: Martin L. Yarmush, Alexander Golberg, Gregor Serša, Tadej Kotnik, Damijan Miklavčič
Journal: Annual Review of Biomedical Engineering (2014)

When high-amplitude, short-duration pulsed electric fields are applied to cells and tissues, the permeability of the cell membranes and tissue is increased. This increase in permeability is currently explained by the temporary appearance of aqueous pores within the cell membrane, a phenomenon termed electroporation. During the past four decades, advances in fundamental and experimental electroporation research have allowed for the translation of electroporation-based technologies to the clinic. In this review, we describe the theory and current applications of electroporation in medicine and then discuss current challenges in electroporation research and barriers to a more extensive spread of these clinical applications.
Early supported discharge services for stroke patients: a meta-analysis of individual patients' data
Authors: Peter Langhorne, Gillian Taylor, Gordon Murray, Martin Dennis, Craig Anderson, Erik Bautz-Holter, Paola Dey, Bent Indredavik, Nancy Mayo, Michael Power, Helen Rodgers, Ole Morten Ronning, Anthony Rudd, Nijasri Suwanwela, Lotta Widen-Holmqvist, Charles Wolfe
Journal: The Lancet (2005)
An Apoptosis Methylation Prognostic Signature for Early Lung Cancer in the IFCT-0002 Trial
Authors: Florence de Fraipont, Guénaëlle Levallet, Christian Creveuil, Emmanuel Bergot, Michèle Beau-Faller, Mounia Mounawar, Nicolas Richard, Martine Antoine, Isabelle Rouquette, Marie-Christine Favrot, Didier Debieuvre, Denis Braun, Virginie Westeel, Elisabeth Quoix, Elisabeth Brambilla, Pierre Hainaut, Denis Moro-Sibilot, Franck Morin, Bernard Milleron, Gérard Zalcman
Journal: Clinical Cancer Research (2012)

To evaluate prognostic and predictive molecular biomarkers in early-stage non-small cell lung carcinoma (NSCLC) receiving neoadjuvant chemotherapy.The IFCT-0002 trial compared two neoadjuvant regimens in 528 stages I to II NSCLC patients. DNA extraction of snap-frozen surgical samples taken from 208 patients receiving gemcitabine-cisplatin or paclitaxel-carboplatin regimens allowed for the identification of 3p allelic imbalance, Ras association domain family 1A (RASSF1A) and death-associated protein kinase 1 (DAPK1) promoter methylation, and epidermal growth factor receptor, K-ras, and TP53 mutations. Multivariate analysis identified prognostic and predictive effects of molecular alterations. A Bootstrapping approach was used to assess stability of the prognostic models generating optimism corrected indexes.RASSF1A methylation correlated significantly with shorter disease-free survival (DFS; adjusted HR = 1.88, 95% CI: 1.25-2.82, P = 0.0048) and shorter median overall survival (OS; adjusted HR = 2.01, 95% CI: 1.26-3.20, P = 0.020). A computed bootstrap resampling strategy led to a prognostic model, including RASSF1A, DAPK1, and tumor stage, dividing patients into three prognostic groups, with median OS ranging from 34 months for high-risk patients (HR for death = 3.85, 95% CI: 1.79-6.40) to more than 84 months for moderate (HR = 1.85, 95% CI: 0.97-3.52) and low-risk patients (reference group; P = 0.00044). In addition, RASSF1A methylation predicted longer DFS in patients treated with paclitaxel-carboplatin compared with gemcitabine-cisplatin (adjusted HR = 0.47, 95% CI: 0.23-0.97, P(interaction) = 0.042).Following neoadjuvant chemotherapy, RASSF1A methylation negatively impacted prognosis of early-stage NSCLC. Along with DAPK1 methylation and tumor stage, RASSF1A methylation allowed definition of three subgroups with strikingly different prognosis. Conversely, significantly longer DFS following paclitaxel-based neoadjuvant chemotherapy for patients whose tumors showed RASSF1A methylation suggested its predictive interest in stages I and II NSCLC.