8-epi PGF2 alpha generation during coronary reperfusion. A potential quantitative marker of oxidant stress in vivo

BACKGROUND: Myocardial reperfusion is believed to be associated with free radical injury. However, indexes of oxidative stress in vivo have been limited by their poor specificity and sensitivity. Isoprostanes are stable products of arachidonic acid formed in a nonenzymatic, free radical-catalyzed manner. We have developed a sensitive and specific assay for one of these compounds, 8-epi prostaglandin (PG) F2 alpha. METHODS AND RESULTS: To address its utility as an index of oxidative stress during coronary reperfusion, we measured urinary levels by gas chromatography/mass spectrometry in a canine model of coronary thrombolysis, in patients with acute myocardial infarction treated with thrombolytic therapy, and in patients after elective coronary artery bypass surgery. Urinary 8-epi PGF2 alpha was unchanged after circumflex artery occlusion in a canine model of coronary thrombolysis (n = 13; 437.2 +/- 56.4 versus 432.7 +/- 55.2 pmol/mmol creatinine) but increased significantly (P < .05) immediately after reperfusion (553.8 +/- 64.7 pmol/mmol). Urinary levels were increased (P < .001) in patients (n = 12) with acute myocardial infarction given lytic therapy (265.8 +/- 40.8 pmol/mmol) compared with age-matched control subjects (n = 20; 91.5 +/- 11.8 pmol/mmol) and patients with stable coronary disease (n = 20; 95.7 +/- 6.3 pmol/mmol). Preoperative levels rose from 113.2 +/- 11.8 to 248.2 +/- 86.3 pmol/mmol at 30 minutes into revascularization to 332.2 +/- 82.6 pmol/mmol by 15 minutes after global myocardial reperfusion (P < .05) and dropped to 181.2 +/- 50.4 pmol/mmol at 30 minutes and 120.2 +/- 9.9 pmol/mmol at 24 hours after bypass surgery (n = 5). Corresponding changes in spin adduct formation, found with electron paramagnetic resonance, were noted in 2 patients. CONCLUSIONS: These data support the hypothesis that free radical generation occurs during myocardial reperfusion. Measurement of isoprostane production may serve as a noninvasive index of oxidative stress.     

Cytokine profiles of stimulated blood lymphocytes in asthmatic and healthy adolescents across the school year

T cell cytokines play an important role in mediating airway inflammation in asthma. The predominance of a Th2 cytokine profile, particularly interleukin (IL)-4 and IL-5, is associated with the pathogenesis and course of asthma. The aim of this study was to test the hypothesis that a stressful life event alters the pattern of cytokine release in asthmatic individuals. Thirteen healthy controls and 21 asthmatic adolescents gave blood samples three times over a semester: midsemester, during the week of final examinations, and 2-3 weeks after examinations. Interferon-gamma (IFN-gamma), IL-2, IL-4, and IL-5 were measured from supernatants of cells stimulated with PHA/PMA for 24 h. Cells from asthmatic subjects released significantly more IL-5 during the examination and postexamination periods, whereas cells from healthy controls released significantly more IL-2 during the midsemester and examination periods, thereby indicating a bias for a Th2-like pattern in asthmatics and a Th1-like pattern in healthy controls. IL-4 and IL-5 production showed a marked decrease during and after examinations in healthy controls, whereas this decline was absent in asthmatics. The ratios of IFN-gamma:IL-4 and IFN-gamma:IL-5 also revealed significant changes in the profile of cytokine release across the semester. These results indicate differential cytokine responses in asthmatics that may become pronounced during periods of cellular activation.     

Implementing total quality management at the U.S. Department of Defense

This paper examines Total Quality Management (TQM) as defined by Dr. W. Edwards Deming including Deming's fourteen points and explains how the United States' Department of Defense (DOD) defines TQM and why TQM is necessary. It also covers how the DOD is planning on implementing TQM and the policy that has been established as guidance in the implementation process.     

The histologic anatomy of the volar plate

The EU Concerted Action Workshop on 11q23 Abnormalities in Hematological Malignancies collected 550 patients with abnormalities involving 11q23. Of these, 53 patients had a translocation involving chromosome 11, breakpoint q23, and chromosome 19, breakpoint p13. Karyogram review enabled each patient to be further defined as t(11;19)(q23;p13.1) (21 patients) or t(11;19)(q23;p13.3) (32 patients). There was a marked difference between the type of banding and the translocation identified: t(11;19)(q23;p13.1) was detected predominantly by R-banding, whereas t(11;19)(q23;p13.3) was detected almost solely by G-banding. Additional change was extremely rare in patients with t(11;19)(q23;p13.1) but occurred in nearly half of the patients with t(11;19)(q23;p13.3). Patients with t(11;19)(q23;p13.1) all had leukemia of a myeloid lineage, mostly acute myeloid leukemia (AML), and were predominantly adult. In contrast patients with t(11;19)(q23;p13.3) had malignancies of both myeloid and lymphoid lineage and were mainly infants less than 1 year old. The survival of both groups of patients was generally poor, over 50% of t(11;19)(q23;p13.1) patients died within 2 years of diagnosis and the median survival of acute lymphoblastic leukemia (ALL) patients with t(11;19)(q23;p13.3) was 17.6 months.     

Tourism‐related waterfront development in historic cities: Malta's Cottonera Project

The emergence of new tourism‐related land uses within historic port cities has brought a range of physical, economic and social benefits. However, there are often associated tensions between the need for economic development and the need to maintain the unique heritage resource that may be a large part of the attraction for visitors. The case of Malta's Cottonera Project—for the waterfront of part of the historic ‘Grand Harbour’—throws these tensions into sharp relief; indeed, the controversy generated by the proposal led to a successful vote of no confidence in the Maltese government. The case illustrates the problematic role of the spatial planning system in seeking to mediate between interests with opposing aims in historic port cities, and the need to apply principles of sustainable regeneration.     

Constructing a short form of the Smoking Consequences Questionnaire with adolescents and young adults.

The goal of the present studies was to construct and validate a short form of the 50-item Smoking Consequences Questionnaire (SCQ; T. H. Brandon & T. B. Baker, 1991), a measure of smoking outcome expectancies. In Study 1, a 21-item short form (S-SCQ) was derived from a sample of 107 young adults previously treated for substance abuse. In Study 2, the measure was cross-validated on 125 adolescents in treatment for substance abuse. Confirmatory factor analyses revealed good model fit and factorial invariance for the 4 S-SCQ subscales across both samples. Validation analyses on each sample found that subscale scores generally correlated significantly with smoking-related variables. The present studies provide initial evidence for the utility of the S-SCQ when used with young adults and adolescents. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cyclosporine in glomerular disease

Cyclosporine was introduced in 1981 as an immunosuppressive agent in renal transplantation. Its use was soon extended to the treatment of various glomerular disorders. In light of its known immunomodulating effects, the use of cyclosporine has been most prominent in those glomerular diseases thought to have an immune basis. The most careful studies of cyclosporine in glomerular diseases have been performed in the pediatric population with idiopathic nephrotic syndrome (i.e., minimal change disease and focal segmental glomerulosclerosis), although data are accumulating regarding efficacy and safety in adults with idiopathic nephrotic syndrome. In patients who are steroid-dependent, cyclosporine therapy can induce complete or partial remission in a significant proportion of cases; success rates in patients with steroid-resistant nephrotic syndrome are less encouraging. Treatment with cyclosporine allows for dose reduction or elimination of corticosteroids, and the consequent salutary effect on growth in the child and glucose and bone metabolism in all patients. Studies that suggest a potential benefit of cyclosporine in recurrent nephrotic syndrome in renal allografts and in other glomerular diseases are also discussed.     

Astrocytic neurotransmitter receptors in situ and in vivo

In the brain, astrocytes are associated intimately with neurons and surround synapses. Due to their close proximity to synaptic clefts, astrocytes are in a prime location for receiving synaptic information from released neurotransmitters. Cultured astrocytes express a wide range of neurotransmitter receptors, but do astrocytes in vivo also express neurotransmitter receptors and, if so, are the receptors activated by synaptically released neurotransmitters? In recent years, considerable efforts has gone into addressing these issues. The experimental results of this effort have been compiled and are presented in this review. Although there are many different receptors which have not been identified on astrocytes in situ, it is clear that astrocytes in situ express a number of different receptors. There is evidence of glutamatergic, GABAergic, adrenergic, purinergic, serotonergic, muscarinic, and peptidergic receptors on protoplasmic, fibrous, or specialized (Bergmann glia, pituicytes, Müller glia) astrocytes in situ and in vivo. These receptors are functionally coupled to changes in membrane potential or to intracellular signaling pathways such as activation of phospholipase C or adenylate cyclase. The expression of neurotransmitter receptors by astrocytes in situ exhibits regional and intraregional heterogeneity and changes during development and in response to injury. There is also evidence that receptors on astrocytes in situ can be activated by neurotransmitter(s) released from synaptic terminals. Given the evidence of extra-synaptic signaling and the expression of neurotransmitter receptors by astrocytes in situ, direct communication between neurons and astrocytes via neurotransmitters could be a widespread form of communication in the brain which may affect many different aspects of brain function, such as glutamate uptake and the modulation of extracellular space.