tbuckley/cabot-search huggingface dataset:
Effect of two breathing exercises (Buteyko and pranayama) in asthma: a randomised controlled trial
Authors: S Cooper
Journal: Thorax (2003)

<b>Background:</b> Patients with asthma are interested in the use of breathing exercises but their role is uncertain. The effects of the Buteyko breathing technique, a device which mimics pranayama (a yoga breathing technique), and a dummy pranayama device on bronchial responsiveness and symptoms were compared over 6 months in a parallel group study. <b>Methods:</b> Ninety patients with asthma taking an inhaled corticosteroid were randomised after a 2 week run in period to Eucapnic Buteyko breathing, use of a Pink City Lung Exerciser (PCLE) to mimic pranayama, or a PCLE placebo device. Subjects practised the techniques at home twice daily for 6 months followed by an optional steroid reduction phase. Primary outcome measures were symptom scores and change in the dose of methacholine provoking a 20% fall in FEV<sub>1</sub> (PD<sub>20</sub>) during the first 6 months. <b>Results:</b> Sixty nine patients (78%) completed the study. There was no significant difference in PD<sub>20</sub> between the three groups at 3 or 6 months. Symptoms remained relatively stable in the PCLE and placebo groups but were reduced in the Buteyko group. Median change in symptom scores at 6 months was 0 (interquartile range −1 to 1) in the placebo group, −1 (−2 to 0.75) in the PCLE group, and −3 (−4 to 0) in the Buteyko group (p=0.003 for difference between groups). Bronchodilator use was reduced in the Buteyko group by two puffs/day at 6 months; there was no change in the other two groups (p=0.005). No difference was seen between the groups in FEV<sub>1</sub>, exacerbations, or ability to reduce inhaled corticosteroids. <b>Conclusion:</b> The Buteyko breathing technique can improve symptoms and reduce bronchodilator use but does not appear to change bronchial responsiveness or lung function in patients with asthma. No benefit was shown for the Pink City Lung Exerciser.
Influence of changes in pancreatic tissue morphology and capillary blood flow on antibiotic tissue concentrations in the pancreas during the progression of acute pancreatitis.
Authors: T Foitzik, H G Hotz, M Kinzig, F Sorgel, H J Buhr
Journal: Gut (1997)

The ability of an antibiotic to reach bactericidal concentrations in tissue depends on numerous factors including tissue composition and regional perfusion. Although necrotising pancreatitis is characterised by progression of pancreatic necrosis over at least 96 hours and microcirculatory alterations, the impact of these changes on the concentration of antibiotics in the pancreas has not yet been investigated.To determine and compare pancreatic tissue concentrations of imipenem and cefotaxime at different stages of acute necrotising pancreatitis in an animal model that has been shown to mimic closely the pathomorphological and bacteriological features of severe human pancreatitis.Acute necrotising pancreatitis was induced in rats by a standardised intraductal infusion of glycodeoxycholic acid and intravenous cerulein. Six hours (n = 16) and 48 hours (n = 16) after induction of pancreatitis, the animals were randomised for intravenous therapy with either imipenem or cefotaxime. Fifteen minutes after injection of the antibiotic, the animals were killed. Blood and the head of the pancreas were collected for determining imipenem or cefotaxime in serum and tissue; the splenic portion of the pancreas was prepared for histological examination. In an additional set of identically treated animals, pancreatic capillary blood flow (PCBF) was assessed by intravital microscopy before induction of acute necrotising pancreatitis and at the time of antibiotic therapy.Imipenem accumulates in the pancreas in the initial phase of acute necrotising pancreatitis characterised by pronounced oedema and decreased PCBF, and tends to decrease with resolution of the oedema and the progression of acinar cell necrosis in the later course of the disease. Concentrations of cefotaxime are low in oedematous pancreatic tissue early after induction of acute necrotising pancreatitis and increase with the resolution of oedema and normalisation of PCBF.Concentrations of antibiotics in the pancreas vary in acute necrotising pancreatitis, depending on changes in pancreatic tissue morphology and capillary blood flow. This suggests that antibiotic tissue concentrations may not be consistent from one agent to another and that efficacy of antibiotics in acute pancreatitis cannot be estimated solely on the basis of their pharmacological and microbiological properties.
Non-cardiovascular effects associated with statins
Authors: C. S. Desai, S. S. Martin, R. S. Blumenthal
Journal: BMJ (2014)

Statins form the pharmacologic cornerstone of the primary and secondary prevention of atherosclerotic cardiovascular disease. In addition to beneficial cardiovascular effects, statins seem to have multiple non-cardiovascular effects. Although early concerns about statin induced hepatotoxicity and cancer have subsided owing to reassuring evidence, two of the most common concerns that clinicians have are myopathy and diabetes. Randomized controlled trials suggest that statins are associated with a modest increase in the risk of myositis but not the risk of myalgia. Severe myopathy (rhabdomyolysis) is rare and often linked to a statin regimen that is no longer recommended (simvastatin 80 mg). Randomized controlled trials and meta-analyses suggest an increase in the risk of diabetes with statins, particularly with higher intensity regimens in people with two or more components of the metabolic syndrome. Other non-cardiovascular effects covered in this review are contrast induced nephropathy, cognition, cataracts, erectile dysfunction, and venous thromboembolism. Currently, systematic reviews and clinical practice guidelines indicate that the cardiovascular benefits of statins generally outweigh non-cardiovascular harms in patients above a certain threshold of cardiovascular risk. Literature is also accumulating on the potential non-cardiovascular benefits of statins, which could lead to novel applications of this class of drug in the future.
HLA-DR antigens in systemic lupus erythematosus: association with specificity of autoantibody responses to nuclear antigens.
Authors: J S Smolen, J H Klippel, E Penner, M Reichlin, A D Steinberg, T M Chused, O Scherak, W Graninger, E Hartter, C C Zielinski
Journal: Annals of the Rheumatic Diseases (1987)

HLA-DR antigens and autoantibodies to the nuclear or cytoplasmic antigens Ro/SSA, La/SSB, Sm, and RNP were determined in North American and Austrian patients with systemic lupus erythematosus (SLE). Analysis of the association of antibodies to these ribonucleic acid (RNA)-protein antigens with HLA-DR antigens showed that HLA-DR3 was related to the presence of anti-Ro/SSA or anti-La/SSB, or both. In contrast, anti-Sm or anti-RNP, or both were associated with HLA-DR4. HLA-DR5 was associated with absence of these autoantibodies. The data extend evidence for the complexity and heterogeneity of SLE. Moreover, they indicate that, in SLE, genes linked to those coding for HLA-DR antigens, are related to the specificity of autoantibody responses rather than to the primary immunological abnormalities of this disorder.
Systems Pharmacology Links GPCRs with Retinal Degenerative Disorders
Authors: Yu Chen, Krzysztof Palczewski
Journal: The Annual Review of Pharmacology and Toxicology (2015)

In most biological systems, second messengers and their key regulatory and effector proteins form links between multiple cellular signaling pathways. Such signaling nodes can integrate the deleterious effects of genetic aberrations, environmental stressors, or both in complex diseases, leading to cell death by various mechanisms. Here we present a systems (network) pharmacology approach that, together with transcriptomics analyses, was used to identify different G protein-coupled receptors that experimentally protected against cellular stress and death caused by linked signaling mechanisms. We describe the application of this concept to degenerative and diabetic retinopathies in appropriate mouse models as an example. Systems pharmacology also provides an attractive framework for devising strategies to combat complex diseases by using (repurposing) US Food and Drug Administration-approved pharmacological agents.
The George E. Brown Memorial Lecture
Authors: NELSON W. BARKER
Journal: Circulation (1958)

The pathogenesis of intravascular thrombosis involves 1 or a combination of 3 factors: an endothelial lesion, a disturbance of blood flow, and hypercoagulability of the blood. The fate of fresh thrombi is probably dependent on the fibrinolytic activity of the plasma. While some tests for coagulation factors have given some positive results among patients with various types of thrombosis, no test has consistently demonstrated its value in predicting a thrombosing tendency. Carefully administered anticoagulant therapy has been effective in the prevention of thrombosis in many patients. Such therapy requires individualization on the basis of frequent laboratory tests and is usually justified only after the patient has suffered one or more episodes of clinical thrombosis. Treatment of acute thrombosis by intravascular injections of fibrinolysins is still in the experimental stage. Recent advances in surgical technic have led to successful restoration of continuity of some of the large arteries previously occluded by thrombosis.
Ventilatory mechanics and expiratory flow limitation during exercise in normal subjects
Authors: Snorri Olafsson, Robert E. Hyatt
Journal: Journal of Clinical Investigation (1969)

We have examined the interrelationships among transpulmonary pressure, flow, and volume during exhausting exercise in 10 normal adult males. Expiratory transpulmonary pressures during exercise were compared with flow-limiting pressures measured at rest by two techniques. In no case did pressures developed during exercise exceed to an appreciable extent the flow-limiting pressures. This indicates that, during near-maximal exercise, ventilation remains efficient as judged in terms of the pressure-volume relationships of the lung. The mechanical properties of the lung do not appear to limit ventilation during exhausting exercise in normal subjects. We could find no relationship between the magnitude of transpulmonary pressure and exercise limitation. There was no evidence that lung mechanics changed during exhausting exercise in normal subjects. The two methods for estimating expiratory flow-limiting pressures, the orifice technique and the isovolume pressure-flow method, gave similar results.
Dietary Patterns and Glucose Tolerance Abnormalities in Chinese Adults
Authors: Yuna He, Guansheng Ma, Fengying Zhai, Yanping Li, Yisong Hu, Edith J.M. Feskens, Xiaoguang Yang
Journal: Diabetes Care (2009)

OBJECTIVE To investigate the association of the dietary pattern with the presence of newly diagnosed glucose tolerance abnormalities among Chinese adults. RESEARCH DESIGN AND METHODS A total of 20,210 adults aged 45–69 years from the 2002 China National Nutrition and Health Survey were included. Information on dietary intake was collected using a validated food frequency questionnaire. Factor analysis and cluster analysis were used to identify the food factors and dietary pattern clusters. RESULTS Four dietary pattern clusters were identified (“Green Water,” “Yellow Earth,” “Western Adopter,” and “New Affluence”). The prevalence of glucose tolerance abnormalities ranged from 3.9% in the Green Water to 8.0% in the New Affluence. After adjustment for area, age, sex, current smoking, and physical activity, subjects in the Yellow Earth cluster (prevalence ratio 1.22 [95% CI 1.04–1.43]) and New Affluence cluster (2.05 [1.76–2.37]) had significantly higher prevalence rates compared with those for the Green Water cluster. After further adjustment for BMI and waist-to-height ratio, the elevated risk in the New Affluence remained statistically significant. CONCLUSIONS Dietary patterns and food factors are associated with the presence of glucose tolerance abnormalities in China, even independent of obesity. A New Affluence diet is an important modifiable risk factor, which needs attention from the prevention point of view.
Genomics of In-Stent Restenosis
Authors: Santhi K. Ganesh, Elizabeth G. Nabel
Journal: Circulation (2005)

nflammation is a key component of atherosclerosis.Abundant preclinical data support the hypothesis that atherosclerosis is a chronic inflammatory disorder. 1,2Indeed, clinical trial data now provide evidence that inflammation, as reflected in serum markers such as C-reactive protein and interleukin-6, is a strong risk factor for the development and progression of atherosclerosis. 3,4The role of genetic factors in determining a predisposition or susceptibility to inflammation that exacerbates atherosclerosis is not fully known.
Review on leptin and adiponectin responses and adaptations to acute and chronic exercise
Authors: A Bouassida, K Chamari, M Zaouali, Y Feki, A Zbidi, Z Tabka
Journal: British Journal of Sports Medicine (2008)

Leptin and adiponectin represent two newly discovered adipose tissue derived hormones; that are both associated with health status and glucose and free fatty acid (FFA) metabolism. Moreover, acute and chronic exercises affect body composition, carbohydrate and lipid metabolism. It is thus interesting to evaluate the effects of physical exercise and training on leptin and adiponectin levels. It seems that leptin concentration is not modified after short-term exercise (<60 min) or exercise that generates an energy expenditure lower than 800 kcal. Leptin levels decrease after long-term exercise (> or =60 min) stimulating FFA release, or after exercise that generates energy expenditure higher than 800 kcal. Adiponectin concentration presents a delayed increase (30 min) after short-term intense exercise (<60 min) performed by trained athletes. For adiponectin, limited data suggest that adiponectin concentration presents a delayed increase (30 min) after short-term intense exercise (<60 min) performed by trained athletes. It seems that adiponectin concentrations do not change in response to long-term exercise (> or =60 min). Short-term training (<12 weeks) and long-term training (> or =12 weeks) show contrasting results regarding leptin and adiponectin. Most training studies which improve fitness levels and affect body composition could decrease leptin and increase adiponectin concentrations.
Gene Expression Signatures for Tumor Progression, Tumor Subtype, and Tumor Thickness in Laser-Microdissected Melanoma Tissues
Authors: Jochen Jaeger, Dirk Koczan, Hans-Juergen Thiesen, Saleh M. Ibrahim, Gerd Gross, Rainer Spang, Manfred Kunz
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To better understand the molecular mechanisms of malignant melanoma progression and metastasis, gene expression profiling was done of primary melanomas and melanoma metastases. Experimental Design: Tumor cell–specific gene expression in 19 primary melanomas and 22 melanoma metastases was analyzed using oligonucleotide microarrays after laser-capture microdissection of melanoma cells. Statistical analysis was done by random permutation analysis and support vector machines. Microarray data were further validated by immunohistochemistry and immunoblotting. Results: Overall, 308 genes were identified that showed significant differential expression between primary melanomas and melanoma metastases (false discovery rate ≤ 0.05). Significantly overrepresented gene ontology categories in the list of 308 genes were cell cycle regulation, mitosis, cell communication, and cell adhesion. Overall, 47 genes showed up-regulation in metastases. These included Cdc6, Cdk1, septin 6, mitosin, kinesin family member 2C, osteopontin, and fibronectin. Down-regulated genes included E-cadherin, fibroblast growth factor binding protein, and desmocollin 1 and desmocollin 3, stratifin/14-3-3σ, and the chemokine CCL27. Using support vector machine analysis of gene expression data, a performance of &amp;gt;85% correct classifications for primary melanomas and metastases was reached. Further analysis showed that subtypes of primary melanomas displayed characteristic gene expression patterns, as do thin tumors (≤1.0 mm Breslow thickness) compared with intermediate and thick tumors (&amp;gt;2.0 mm Breslow thickness). Conclusions: Taken together, this large-scale gene expression study of malignant melanoma identified molecular signatures related to metastasis, melanoma subtypes, and tumor thickness. These findings not only provide deeper insights into the pathogenesis of melanoma progression but may also guide future research on innovative treatments.
Effect of disease modifying agents on the lipid profiles of patients with rheumatoid arthritis
Authors: R Munro, E Morrison, A G McDonald, J A Hunter, R Madhok, H A Capell
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVE</h3> To determine the effect of intramuscular gold and oral hydroxychloroquine(HCQ) on the lipid profile of patients with rheumatoid arthritis (RA). <h3>METHOD</h3> A prospective randomised clinical trial of 12 months' duration was performed in 100 RA patients. Data on clinical and laboratory parameters of disease activity, and fasting serum lipid samples was collected at baseline and at three monthly intervals over one year. <h3>RESULTS</h3> The expected second line response was seen with no significant difference in efficacy between the groups at 12 months. The HCQ group had a significant overall improvement in their lipid profile while there was a trend for lipid profiles in the gold group to worsen. <h3>CONCLUSIONS</h3> HCQ is an effective second line agent that has beneficial effects on serum lipids. This should be taken into account when choosing a disease modifying anti-rheumatic drug in patients who suffer from RA and who have significant cardiovascular risk factors.
Effects of Estrogen on the Vascular Injury Response in Estrogen Receptor α,β (Double) Knockout Mice
Authors: Richard H. Karas, Henny Schulten, Gary Pare, Mark J. Aronovitz, Claes Ohlsson, Jan-Ake Gustafsson, Michael E. Mendelsohn
Journal: Circulation Research (2001)

The two known estrogen receptors, ERalpha and ERbeta, mediate the effects of estrogen in all target tissues, including blood vessels. We have shown previously that estrogen inhibits vascular injury response to the same extent in female wild-type (WT), ERalpha knockout (ERalphaKO(CH)), and ERbeta knockout (ERbetaKO(CH)) mice. We generated mice harboring disruptions of both ERalpha and ERbeta genes (ERalpha,betaKO(CH)) by breeding and studied the effect of 17beta-estradiol (E2) on vascular injury responses in ovariectomized female ERalpha,betaKO(CH) mice and WT littermates. E2 inhibited increases in vascular medial area following injury in the WT mice but not in the ERalpha,betaKO(CH) mice, demonstrating for the first time that the two known estrogen receptors are necessary and sufficient to mediate estrogen inhibition of a component of the vascular injury response. Surprisingly, as in WT littermates, E2 still significantly increased uterine weight and inhibited vascular smooth muscle cell (VSMC) proliferation following injury in the ERalpha,betaKO(CH) mice. These data support that the role of estrogen receptors differs for specific components of the vascular injury response in the ERalpha,betaKO(CH) mice. The results leave unresolved whether E2 inhibition of VSMC proliferation in ERalpha,betaKO(CH) mice is caused by a receptor-independent mechanism, an unidentified receptor responsive to estrogen, or residual activity of the ERalpha splice variant reported previously in the parental ERalphaKO(CH) mice. These possibilities may be resolved by studies of mice in which ERalpha has been fully disrupted (ERalphaKO(St)), which are in progress.
Dechloriation mechanisms of chlorinated olefins.
Authors: R A Van Dyke
Journal: Environmental Health Perspectives (1977)

The dechlorination of chlorinated hydrocarbons has been examined in detail. The reaction is catalyzed by cytochrome P-450 and occurs optimally in the presence of oxygen although some dechlorination may occur under anaerobic conditions. Halothane has been shown to undergo an oxidative dechlorination and a reductive defluorination. Enzymatic attack of chlorinated olefins and hydrocarbons is not on the carbon--halogen bond. Oxidative dechlorination of hydrocarbons is apparently initiated by an attack on the carbon atom and the halogen is then released from the oxidized carbon. The chlorinated olefins, on the other hand, are not easily dechlorinated enzymatically. The chlorines migrate readily across the double bond, therefore, cyclic chloronium ions must occur as intermediates. It is not clear at this time if epoxides are also intermediates in this conversion.
Bringing preconditioning and postconditioning into focus
Authors: D GARCIADORADO, J VINTENJOHANSEN, H PIPER
Journal: Cardiovascular Research (2006)

After many years of debate during which the preponderance of opinion was skeptical about the experimental and clinical existence of reperfusion injury (with attitudes ranging between polite condescendence and overt denial), it can be said that the controversy has been now largely resolved, and that the death of cardiomyocytes during reperfusion is now generally admitted as a fact. Perhaps this agreement is still more firm in the experimental literature than in clinical cardiology. The discovery of the phenomenon of postconditioning [1] has undoubtedly contributed to this change of opinion. The first reports of postconditioning the human heart by Laskey et al. and Ovize et al. certainly support the concept of reperfusion injury as a clinical entity that can be measured even in a small group of patients [2,3]. The report by Zhao et al. [1] has aroused a renewed interest in the mechanisms of cell death during ischemia–reperfusion, and of endogenous protection against it [4]. Postconditioning is as powerful as preconditioning and has the potential of being clinically applicable in the most common situation of unexpected coronary occlusion and acute myocardial infarction [3]. Yet, the mechanisms by which postconditioning limits reperfusion-induced cell death and the relationship between the mechanisms in pre- and postconditioning are far from being completely understood. The present Spotlight Issue presents a series of review articles with the aim of providing an up-to-date overview of the state of the art in the rapidly moving field of research on endogenous protection against myocardial cell death secondary to ischemia–reperfusion.

The reason for the resurrection of this field of research is that it is necessary to gain an adequate … 

* Corresponding author. Tel.: +34 93 489 4038; fax: +34 93 489 4032. Email address: dgdorado{at}vhebron.net
Paradoxical responses in non-HIV-infected patients with peripheral lymph node tuberculosis
Authors: Oh-Hyun Cho, Ki-Ho Park, Tark Kim, Eun Hee Song, Eun-Young Jang, Eun Jung Lee, Yong Pil Chong, Sang-Ho Choi, Sang-Oh Lee, Jun Hee Woo, Yang Soo Kim, Sung-Han Kim
Journal: Journal of Infection (2009)