tbuckley/cabot-search huggingface dataset:
Prudent Strategies for Elective Red Blood Cell Transfusion
Authors: H G Welch, K R Meehan, L T Goodnough
Journal: Annals of Internal Medicine (1992)

Objective: To review the literature on the appropriateness of red blood cell transfusion and current physician practice, with emphasis on the physiologic and symptomatic implications of elective transfusion in the treatment of anemia. Data Sources: Studies on the therapeutic use of red blood cell transfusion were identified through a search of MEDLINE (1966 to the present) and through a manual review of bibliographies of identified articles. In addition, evidence was solicited from selected experts in the field and recent consensus panels that have developed transfusion guidelines. Data Synthesis: No controlled trials of blood transfusion were identified, but data were available on four issues relevant to transfusion practice: current physician practice and evidence for excessive use of red blood cell transfusion; physiologic adaptation to anemia; human tolerance of low hemoglobin levels; and strategies for reducing homologous transfusion requirements. Conclusions: Despite the recent decline in red blood cell use because of concerns about infection, current transfusion practice remains variable because physicians have disparate views about its appropriateness. The remarkable human tolerance of anemia suggests that clinicians can accept hemoglobin levels above 70 g/L (7 g/dL) in most patients with self-limited anemia. In patients with impaired cardiovascular status or with anemias that will not resolve spontaneously, however, the data are insufficient to determine minimum acceptable hemoglobin levels, and therapy must be guided by the clinical situation. Several therapeutic strategies and pharmacologic interventions are available in the perioperative and non-operative settings to further reduce red blood cell use.
Development of Allergic Inflammation in a Murine Model of Asthma Is Dependent on the Costimulatory Receptor Ox40
Authors: Amha Gebre-Hiwot Jember, Riaz Zuberi, Fu-Tong Liu, Michael Croft
Journal: The Journal of Experimental Medicine (2001)

Asthma is thought to result from an abnormal expansion of CD4 T cells reactive with airborne allergens, and pathology is controlled by several cytokines of the T helper type 2 (Th2) family. The exact molecules which are involved in generating allergen-reactive T cells are not clear. Studies with blocking reagents or knockout animals have shown that the CD28/B7 interaction partially controls development of allergic asthma in mouse models, but may not be the sole molecule involved. In this report, we have investigated the role of the tumor necrosis factor receptor family member OX40 in allergic inflammation using OX40-deficient mice. OX40 has been shown to participate in regulating clonal expansion and memory development of CD4 T cells and may synergize with CD28. Our studies demonstrate that OX40−/− mice, primed with the model allergen ovalbumin and challenged through the airways with aerosolized antigen, are severely impaired in their ability to generate a Th2 response characterized by high levels of interleukin (IL)-5, IL-4, and immunoglobulin E. Moreover, OX40−/− mice exhibit diminished lung inflammation, including an 80–90% reduction in eosinophilia and mucus production, less goblet cell hyperplasia, and significantly attenuated airway hyperreactivity. These studies highlight the potential importance of OX40 in development of allergic asthma and suggest that targeting OX40 may prove useful therapeutically.
Suprascapular nerve block (using bupivacaine and methylprednisolone acetate) in chronic shoulder pain
Authors: E M Shanahan
Journal: Annals of the Rheumatic Diseases (2003)

Shoulder pain from inflammatory arthritis and/or degenerative disease is a common cause of morbidity in the community. It is difficult to treat and there are limited data on the efficacy of most interventions. Suprascapular nerve block has shown promise in limited trials in reducing shoulder pain. There have been no large randomised placebo controlled trials examining the efficacy of suprascapular nerve block for shoulder pain in arthritis and/or degenerative disease using pain and disability end points.To perform a randomised, double blind, placebo controlled trial of the efficacy of suprascapular nerve block for shoulder pain in rheumatoid arthritis (RA) and/or degenerative disease of the shoulder.83 people with chronic shoulder pain from degenerative disease or RA took part in the trial. If a person had two painful shoulders, these were randomised separately. A total of 108 shoulders were randomised. Patients in the group receiving active treatment had a single suprascapular nerve block following the protocol described by Dangoisse et al, while those in the other group received a placebo injection of normal saline administered subcutaneously. The patients were followed up for 12 weeks by an observer who was unaware of the randomisation and reviewed at weeks 1, 4, and 12 after the injection. Pain, disability, and range of movement data were gathered.Clinically and statistically significant improvements in all pain scores, all disability scores, and some range of movement scores in the shoulders receiving suprascapular nerve block compared with those receiving placebo were seen at weeks 1, 4, and 12. There were no significant adverse effects in either group.Suprascapular nerve block is a safe and efficacious treatment for the treatment of shoulder pain in degenerative disease and/or arthritis. It improves pain, disability, and range of movement at the shoulder compared with placebo. It is a useful adjunct treatment for the practising clinician to assist in the management of a difficult and common clinical problem.
Steroid-Induced Pancreatitis
Authors: Robert W. Schrier
Journal: JAMA (1965)

THE COMPLICATIONS of therapy with adrenocortical hormones have been reviewed extensively, but the pancreatic abnormalities which occur in association with administration of steroids rarely have been included.<sup>1</sup> A postmortem study by Carone and Liebow<sup>2</sup>revealed histologic evidence of acute pancreatitis, or peripancreatic fat necrosis, in 16 of 54 patients treated with corticotropin or adrenal steroids. In a control group of 54 patients of comparable age and with similar major diseases, only two had these pathologic changes. The clinical diagnosis of pancreatitis was not made in any of these patients. In 1961 Nelp<sup>3</sup>reviewed the literature and reported six of his own cases of clinically manifest acute pancreatitis associated with the administration of adrenal steroids. To our knowledge, no additional cases have been reported. In 12 of 14 previously reported instances of symptomatic pancreatitis induced by steroids, the diagnosis was not made until exploratory surgery or autopsy.<sup>3-8</sup>
Hyperhomocysteinemia Confers an Independent Increased Risk of Atherosclerosis in End-Stage Renal Disease and Is Closely Linked to Plasma Folate and Pyridoxine Concentrations
Authors: Killian Robinson, Anjan Gupta, Vincent Dennis, Kristopher Arheart, Debashish Chaudhary, Ralph Green, Paul Vigo, Ellen L. Mayer, Jacob Selhub, Michael Kutner, Donald W. Jacobsen
Journal: Circulation (1996)

A high level of total plasma homocysteine is a risk factor for atherosclerosis, which is an important cause of death in renal failure. We evaluated the role of this as a risk factor for vascular complications of end-stage renal disease.Total fasting plasma homocysteine and other risk factors were documented in 176 dialysis patients (97 men, 79 women; mean age, 56.3 +/- 14.8 years). Folate, vitamin B12, and pyridoxal phosphate concentrations were also determined. The prevalence of high total homocysteine values was determined by comparison with a normal reference population, and the risk of associated vascular complications was estimated by multiple logistic regression. Total homocysteine concentration was higher in patients than in the normal population (26.6 +/- 1.5 versus 10.1 +/- 1.7 mumol/L; P < .01). Abnormally high concentrations (> 95th percentile for control subjects, 16.3 mumol/L) were seen in 149 patients (85%) with end-stage renal disease (P < .001). Patients with a homocysteine concentration in the upper two quintiles (> 27.8 mumol/L) had an independent odds ratio of 2.9 (CI, 1.4 to 5.8; P = .007) of vascular complications. B vitamin levels were lower in patients with vascular complications than in those without. Vitamin B6 deficiency was more frequent in patients than in the normal reference population (18% versus 2%; P < .01).A high total plasma homocysteine concentration is an independent risk factor for atherosclerotic complications of end-stage renal disease. Such patients may benefit from higher doses of B vitamins than those currently recommended.
Effects of murine recombinant interleukin 1 on synovial joints in mice: measurement of patellar cartilage metabolism and joint inflammation.
Authors: A A van de Loo, W B van den Berg
Journal: Annals of the Rheumatic Diseases (1990)

Murine recombinant interleukin 1 was injected intra-articularly into mice. It induced a clear effect on patellar cartilage within 24 hours. A low dose of interleukin 1 (1 ng) elicited a significant reduction in [35S]sulphate incorporation (50%) into proteoglycans and an accelerated breakdown (twofold) of 35S prelabelled proteoglycan. Proteoglycan breakdown returned to normal rates (approximately 10%/day) 48 hours after a single interleukin 1 injection. Recovery of proteoglycan synthesis was delayed by up to 72 hours, however, which implies that repair of the depleted cartilage matrix is retarded. Interleukin 1 induced only minor joint inflammation, too slight to be held responsible for the strong suppression of proteoglycan synthesis. Vehement joint inflammation was found after repeated interleukin 1 injections. The plasma extravasation and massive infiltration and exudation of leucocytes, predominantly polymorphonuclear leucocytes, were not a mere summation of single interleukin 1 effects, but point to interleukin 1 induced local hypersensitivity. The cartilage matrices of patella and femur were heavily depleted. Measurement of the extent of loss of 35S prelabelled proteoglycan and the prolonged inhibition of [35S]sulphate incorporation indicate that both inhibition of proteoglycan synthesis and enhanced loss of proteoglycan contributed substantially to this depletion.
Chronic effects of ozone in children
Authors: J. Sunyer
Journal: European Respiratory Journal (2003)

Children are not little adults in terms of environmental exposure. They have a unique vulnerability, given their developmental stage and their higher exposure. Lung function in childhood increases linearly with age and height until the adolescent growth spurt 1. Studies on failure to maintain the predicted lung-function growth-curve during pre-adolescence are pertinent, both from a research and a public health perspective and are easier to conduct than studies in adulthood, given the absence of smoking. Ozone is the most important photochemical oxidant in the troposphere. It is formed by photochemical reactions in the presence of precursor pollutants released by motor vehicles. As a result of its photochemical origin, O3 concentrations are much higher in summer.

Change in lung function (forced vital capacity, FVC; forced expiratory volume in one second, FEV1, mean maximal expiratory flow) between a pre- and a post-summer test was negatively associated with the cumulative O3 mean in a study conducted in Austria 2. In nine areas without major industrial sites, 1,150 children aged between 8–11 yrs were followed during a 3–yr period, performing 6 lung function tests. A further analysis showed the effect of O3 to be independent of particles and nitrogen dioxide 3. These results were not replicated by the …
Endothelin receptor antagonists in pulmonary arterial hypertension
Authors: J. Dupuis, M. M. Hoeper
Journal: European Respiratory Journal (2008)

The endothelin (ET) system, especially ET-1 and the ET A and ET B receptors, has been implicated in the pathogenesis of pulmonary arterial hypertension (PAH). Together with prostanoids and phosphodiesterase 5 inhibitors, ET receptor antagonists have become mainstays in the current treatment of PAH. Three substances are currently available for the treatment of PAH. One of these substances, bosentan, blocks both ET A and ET B receptors, whereas the two other compounds, sitaxsentan and ambrisentan, are more selective blockers of the ET A receptor. There is ongoing debate as to whether selective or nonselective ET receptor blockade is advantageous in the setting of PAH, although there is no clear evidence that receptor selectivity is relevant with regard to the clinical effects of these drugs. For the time being, other features, such as safety profiles and the potential for pharmacokinetic interactions with other drugs used in the treatment of PAH, may be more important than selectivity or nonselectivity when selecting treatments for individual patients.
Molecular mechanisms of cardiovascular disease in OSAHS: the oxidative stress link
Authors: L Lavie, P Lavie
Journal: European Respiratory Journal (2009)

Obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is a highly prevalent breathing disorder in sleep that is an independent risk factor for cardiovascular morbidity and mortality. A large body of evidence, including clinical studies and cell culture and animal models utilising intermittent hypoxia, delineates the central role of oxidative stress in OSAHS as well as in conditions and comorbidities that aggregate with it. Intermittent hypoxia, the hallmark of OSAHS, is implicated in promoting the formation of reactive oxygen species (ROS) and inducing oxidative stress. The ramifications of increased ROS formation are pivotal. ROS can damage biomolecules, alter cellular functions and function as signalling molecules in physiological as well as in pathophysiological conditions. Consequently, they promote inflammation, endothelial dysfunction and cardiovascular morbidity. Oxidative stress is also a crucial component in obesity, sympathetic activation and metabolic disorders such as hypertension, dyslipidaemia and type 2 diabetes/insulin resistance, which aggregate with OSAHS. These conditions and comorbidities could result directly from the oxidative stress that is characteristic of OSAHS or could develop independently. Hence, oxidative stress represents the common underlying link in OSAHS and the conditions and comorbidities that aggregate with it.
Lymph node staging in gastric cancer: new criteria, old problems
Authors: Stefano Rausei, Gianlorenzo Dionigi, Laura Ruspi, Ilaria Proserpio, Federica Galli, Fabio Tirotta, Francesco Frattini, Francesca Rovera, Luigi Boni, Graziella Pinotti, Renzo Dionigi
Journal: International Journal of Surgery (2013)
Comparative Genomics Reveals Adaptive Protein Evolution and a Possible Cytonuclear Incompatibility between European and American Eels
Authors: Pierre-Alexandre Gagnaire, Eric Normandeau, Louis Bernatchez
Journal: Molecular Biology and Evolution (2012)

During the early stages of speciation, interspecific gene flow may be impeded by deleterious epistatic interactions in hybrids, which maintain parental allelic combinations at the speciation genes. The resulting semipermeable nature of the barrier to interspecific gene flow provides a valuable framework to identify the genes involved in hybrid mortality or sterility, as well as the evolutionary mechanisms that initially caused their divergence. The two Atlantic eels Anguilla anguilla and A. rostrata are partially isolated sister species that naturally hybridize, but whose genetic basis of postzygotic isolation remains unknown. We collected high-throughput sequencing data from the transcriptomes of 58 individuals and discovered 94 genes showing differentially fixed mutations between species. Evidence for positive selection at nuclear diagnostic genes was obtained using multilocus extensions of the McDonald–Kreitman test with polymorphism data from each species. In contrast, mitochondrial protein-coding genes experienced strong purifying selection and mostly diverged at synonymous sites, except for the mt-atp6 gene, which showed an atypically high nonsynonymous to synonymous rate ratio. Nuclear-encoded protein interactors of the mt-atp6 gene in the ATP synthase complex were significantly overrepresented in the list of nuclear diagnostic genes. Further analysis of resequencing data showed that positive selection has operated at both the mt-atp6 gene and its nuclear interactor atp5c1. These findings suggest that a cytonuclear incompatibility caused by a disruption of normal ATP synthase function in hybrids contributes to partial reproductive isolation between European and American eels.
Predictive Factors of Acute Rejection after Early Cyclosporine Withdrawal in Renal Transplant Recipients Who Receive Mycophenolate Mofetil
Authors: Marc Hazzan, Myriam Labalette, Marie Christine Copin, Franc[COMBINING CEDILLA]ois Glowacki, Franc[COMBINING CEDILLA]ois Provo[Combining Circumflex Accent]t, Franc[COMBINING CEDILLA]ois-René Pruv, Christian Noe[Combining Diaeresis]l
Journal: Journal of the American Society of Nephrology (2005)

The aim of this randomized, open-labeled trial was to compare the incidence of acute rejection after an early (3 mo posttransplantation) withdrawal of cyclosporine (CsA) or mycophenolate mofetil (MMF) in renal transplantation. Among 218 eligible recipients, 108 nonsensitized, rejection-free patients who were under a triple drug regimen (CsA-MMF-prednisone) and had received a first kidney from a deceased donor were enrolled. At 3 mo after graft, they were gradually withdrawn from CsA (MMF group, n = 54) or MMF (CsA group, n = 54). A graft biopsy and a pharmacokinetic study of CsA and mycophenolic acid were systematically performed before the randomization. At 1 yr, graft and patient survival rates were 100% in each group. Renal function was improved in the MMF group compared with the CsA group (Cockcroft calculated clearance 64.7 +/- 18.7 versus 56.5 +/- 18.0 ml/min; P = 0.023). However, the probability of acute rejection was higher in the MMF group (18.5 versus 5.6%; P = 0.045). The 10 patients who developed acute rejection after CsA withdrawal had a significantly higher incidence of borderline changes on the randomization biopsy than the 44 rejection-free patients (five of 10 versus eight of 44; P = 0.034), and they displayed a lower area under the curve of mycophenolic acid (43 +/- 9 versus 58 +/- 22 mg/h per L; P = 0.045). Multivariate analysis confirmed that borderline changes and area under the curve of mycophenolic acid were significant risk factors of acute rejection after CsA discontinuation. It is concluded that a systematic graft biopsy and a pharmacokinetic study of mycophenolic acid are needed to reduce the risk for acute rejection after CsA withdrawal.
Whole-Blood Tissue Factor Procoagulant Activity Is Elevated in Type 1 Diabetes
Authors: Anamika Singh, Guenther Boden, Carol Homko, Jay Gunawardana, A. Koneti Rao
Journal: Diabetes Care (2012)

OBJECTIVE To determine tissue factor procoagulant activity (TF-PCA) in patients with type 1 diabetes and to examine effects of hyperglycemia and hyperglycemia plus hyperinsulinemia on TF-PCA. RESEARCH DESIGN AND METHODS We have determined circulating TF-PCA and other coagulation factors under basal (hyperglycemic) conditions, after acute correction of hyperglycemia, in response to 24 h of selective hyperglycemia, and in response to 24 h of hyperglycemia plus hyperinsulinemia in nine type 1 diabetic patients and in seven nondiabetic control subjects. RESULTS As shown previously in patients with type 2 diabetes, basal TF-PCA and plasma coagulation factor VIIa (FVIIa) were higher in patients with type 1 diabetes than in nondiabetic control subjects. However, in contrast with type 2 diabetes, normalizing glucose did not decrease the elevated TF-PCA levels, and raising glucose or glucose plus insulin levels did not increase TF-PCA. CONCLUSIONS Patients with type 1 diabetes have elevated circulating TF-PCA and FVIIa levels and are in a procoagulant state that may predispose them to acute cardiovascular events. The mechanisms regulating TF-PCA in patients with type 1 and type 2 diabetes are different and should be further explored.
Impact of expression differences of kallikrein-related peptidases and of uPA and PAI-1 between primary tumor and omentum metastasis in advanced ovarian cancer
Authors: J. Dorn, N. Harbeck, R. Kates, A. Gkazepis, A. Scorilas, A. Soosaipillai, E. Diamandis, M. Kiechle, B. Schmalfeldt, M. Schmitt
Journal: Annals of Oncology (2010)
Mitochondrial Genes and Mammalian Phylogenies: Increasing the Reliability of Branch Length Estimation
Authors: P S Corneli, R H Ward
Journal: Molecular Biology and Evolution (2000)

Since branch lengths provide important information about the timing and the extent of evolutionary divergence among taxa, accurate resolution of evolutionary history depends as much on branch length estimates as on recovery of the correct topology. However, the empirical relationship between the choice of genes to sequence and the quality of branch length estimation remains ill defined. To address this issue, we evaluated the accuracy of branch lengths estimated from subsets of the mitochondrial genome for a mammalian phylogeny with known subordinal relationships. Using maximum-likelihood methods, we estimated branch lengths from an 11-kb sequence of all 13 protein-coding genes and compared them with estimates from single genes (0.2-1.8 kb) and from 7 different combinations of genes (2-3.5 kb). For each sequence, we separated the component of the log-likelihood deviation due to branch length differences associated with alternative topologies from that due to those that are independent of the topology. Even among the sequences that recovered the same tree topology, some produced significantly better branch length estimates than others did. The combination of correct topology and significantly better branch length estimation suggests that these gene combinations may prove useful in estimating phylogenetic relationships for mammalian divergences below the ordinal level. Thus, the proper choice of genes to sequence is a critical factor for reliable estimation of evolutionary history from molecular data.
Predicting worsening asthma control following the common cold
Authors: M. J. Walter, M. Castro, S. J. Kunselman, V. M. Chinchilli, M. Reno, T. P. Ramkumar, P. C. Avila, H. A. Boushey, B. T. Ameredes, E. R. Bleecker, W. J. Calhoun, R. M. Cherniack, T. J. Craig, L. C. Denlinger, E. Israel, J. V. Fahy, N. N. Jarjour, M. Kraft, S. C. Lazarus, R. F. Lemanske, R. J. Martin, S. P. Peters, J. W. Ramsdell, C. A. Sorkness, E. R. Sutherland, S. J. Szefler, S. I. Wasserman, M. E. Wechsler
Journal: European Respiratory Journal (2008)

The asthmatic response to the common cold is highly variable, and early characteristics that predict worsening of asthma control following a cold have not been identified. In this prospective multicentric cohort study of 413 adult subjects with asthma, the mini-Asthma Control Questionnaire (mini-ACQ) was used to quantify changes in asthma control and the Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) to measure cold severity. Univariate and multivariable models were used to examine demographic, physiological, serological and cold-related characteristics for their relationship to changes in asthma control following a cold. Clinically significant worsening of asthma control was observed following a cold (mean± sd increase in mini-ACQ score of 0.69±0.93). Univariate analysis demonstrated that season, centre location, cold duration and cold severity measurements were all associated with a change in asthma control. Multivariable analysis of the covariates available within the first 2 days of cold onset revealed that the day 2 and cumulative sum of day 1 and 2 WURSS-21 scores were significant predictors of the subsequent changes in asthma control. In asthmatic subjects, cold severity within the first 2 days can be used to predict subsequent changes in asthma control. This information may help clinicians prevent deterioration in asthma control following a cold.