Louisiana State University in Shreveport

The objective of this study was to determine whether endogenous nitric oxide (NO) inhibits leukocyte adhesion to vascular endothelium. This was accomplished by superfusing a cat mesenteric preparation with inhibitors of NO production, NG-monomethyl-L-arginine (L-NMMA) or NG-nitro-L-arginine methyl ester (L-NAME), and observing single (30-microns diameter) venules by intravital video microscopy. Thirty minutes into the superfusion period the number of adherent and emigrated leukocytes, the erythrocyte velocity, and the venular diameter were measured; venular blood flow and shear rate were calculated from the measured parameters. The contribution of the leukocyte adhesion glycoprotein CD11/CD18 was determined using the CD18-specific monoclonal antibody IB4. Both inhibitors of NO production increased leukocyte adherence more than 15-fold. Leukocyte emigration was also enhanced, whereas venular shear rate was reduced by nearly half. Antibody IB4 abolished the leukocyte adhesion induced by L-NMMA and L-NAME. Incubation of isolated cat neutrophils with L-NMMA, but not L-NAME, resulted in direct upregulation of CD11/CD18 as assessed by flow cytometry. Decrements in venular shear rate induced by partial occlusion of the superior mesenteric artery in untreated animals revealed that only a minor component of L-NAME-induced leukocyte adhesion was shear rate-dependent. The L-NAME-induced adhesion was inhibited by L-arginine but not D-arginine. These data suggest that endothelium-derived NO may be an important endogenous modulator of leukocyte adherence and that impairment of NO production results in a pattern of leukocyte adhesion and emigration that is characteristic of acute inflammation.

BACKGROUND: This study was conducted to validate a shortened version of the Rapid Estimate of Adult Literacy in Medicine (REALM). This screening instrument is designed to be used in public health and primary care settings to identify patients with low reading levels. It provides reading grade estimates for patients who read below a ninth-grade level. The REALM can be administered in one to two minutes by personnel with minimal training. METHODS: Two hundred and three patients in four university hospital clinics (internal medicine, family practice, ambulatory care, and obstetrics/gynecology) were given the REALM and three other standardized reading tests: the reading recognition section of the Peabody Individual Achievement Test-Revised (PIAT-R), the Wide Range Achievement Test-Revised (WRAT-R), and the Slosson Oral Reading Test-Revised (SORT-R). One hundred inmates at a state prison were also given the REALM twice, one week apart, to determine test-retest reliability. RESULTS: The REALM correlated well with the three other tests. (Correlation coefficients were 0.97 [PIAT-R], 0.96 [SORT-R], and 0.88 [WRAT-R].) All correlations were significant at P < .0001. Test-retest reliability was 0.99 (P < .001). CONCLUSIONS: The REALM provides an estimate of patient reading ability, displays excellent concurrent validity with standardized reading tests, and is a practical instrument for busy primary care settings.

Inflammation plays an important role in the pathogenesis of ischemic stroke and other forms of ischemic brain injury. Experimentally and clinically, the brain responds to ischemic injury with an acute and prolonged inflammatory process, characterized by rapid activation of resident cells (mainly microglia), production of proinflammatory mediators, and infiltration of various types of inflammatory cells (including neutrophils, different subtypes of T cells, monocyte/macrophages, and other cells) into the ischemic brain tissue. These cellular events collaboratively contribute to ischemic brain injury. Despite intense investigation, there are still numerous controversies concerning the time course of the recruitment of inflammatory cells in the brain and their pathogenic roles in ischemic brain injury. In this review, we provide an overview of the time-dependent recruitment of different inflammatory cells following focal cerebral I/R. We discuss how these cells contribute to ischemic brain injury and highlight certain recent findings and currently unanswered questions about inflammatory cells in the pathophysiology of ischemic stroke.

Multiple organ failure (MOF) has reached epidemic proportions in most intensive care units and is fast becoming the most common cause of death in the surgical intensive care unit. Furthermore, in spite of the development of successive generations of new and more powerful antibiotics and increasing sophisticated techniques of organ support, our ability to salvage patients once MOF has become established has not appreciably improved over the last two decades. Clearly, new therapeutic strategies aimed at preventing or limiting the development of the physiologic abnormalities that induce organ failure are needed to improve survival in these critically ill patients. Based on our rapidly increasing knowledge of the mechanisms of MOF and the fruits of molecular biology, a number of new therapeutic approaches are in various stages of development. To effectively use these new therapeutic options as they become available, it is necessary to have a clear understanding of the pathophysiology of MOF. Thus, the goals of this review are to integrate the vast amount of new information on the basic biology of MOF and to focus special attention on the potential therapeutic consequences of these recent advances in our understanding of this complex and perplexing syndrome.

BACKGROUND: Previous studies have shown that calcium-channel blockers increase morbidity and mortality in patients with chronic heart failure. We studied the effect of a new calcium-channel blocker, amlodipine, in patients with severe chronic heart failure. METHODS: We randomly assigned 1153 patients with severe chronic heart failure and ejection fractions of less than 30 percent to double-blind treatment with either placebo (582 patients) or amlodipine (571 patients) for 6 to 33 months, while their usual therapy was continued. The randomization was stratified on the basis of whether patients had ischemic or nonischemic causes of heart failure. The primary end point of the study was death from any cause and hospitalization for major cardiovascular events. RESULTS: Primary end points were reached in 42 percent of the placebo group and 39 percent of the amlodipine group, representing a 9 percent reduction in the combined risk of fatal and nonfatal events with amlodipine (95 percent confidence interval, 24 percent reduction to 10 percent increase; P=0.31). A total of 38 percent of the patients in the placebo group died, as compared with 33 percent of those in the amlodipine group, representing a 16 percent reduction in the risk of death with amlodipine (95 percent confidence interval, 31 percent reduction to 2 percent increase; P=0.07). Among patients with ischemic heart disease, there was no difference between the amlodipine and placebo groups in the occurrence of either end point. In contrast, among patients with nonischemic cardiomyopathy, amlodipine reduced the combined risk of fatal and nonfatal events by 31 percent (P=0.04) and decreased the risk of death by 46 percent (P<0.001). CONCLUSIONS: Amlodipine did not increase cardiovascular morbidity or mortality in patients with severe heart failure. The possibility that amlodipine prolongs survival in patients with nonischemic dilated cardiomyopathy requires further study.

The concept of health literacy evolved from a history of defining, redefining, and quantifying the functional literacy needs of the adult population. Along with these changes has come the recognition that sophisticated literacy skills are increasingly needed to function in society and that low literacy may have an effect on health and health care. We present a brief history of literacy in the United States, followed by a discussion of the origins and conceptualization of health literacy. Increased attention to this important issue suggests the need to review existing definitions of the term "health literacy," because despite the growing interest in this field, one question that persists is, "What is health literacy?"

BACKGROUND: The outcome of cardiogenic shock complicating myocardial infarction has not appreciably changed in the last 30 years despite the development of various percutaneous mechanical circulatory support options. It is clear that there are varying degrees of cardiogenic shock but there is no robust classification scheme to categorize this disease state. METHODS: A multidisciplinary group of experts convened by the Society for Cardiovascular Angiography and Interventions was assembled to derive a proposed classification schema for cardiogenic shock. Representatives from cardiology (interventional, advanced heart failure, noninvasive), emergency medicine, critical care, and cardiac nursing all collaborated to develop the proposed schema. RESULTS: A system describing stages of cardiogenic shock from A to E was developed. Stage A is "at risk" for cardiogenic shock, stage B is "beginning" shock, stage C is "classic" cardiogenic shock, stage D is "deteriorating", and E is "extremis". The difference between stages B and C is the presence of hypoperfusion which is present in stages C and higher. Stage D implies that the initial set of interventions chosen have not restored stability and adequate perfusion despite at least 30 minutes of observation and stage E is the patient in extremis, highly unstable, often with cardiovascular collapse. CONCLUSION: This proposed classification system is simple, clinically applicable across the care spectrum from pre-hospital providers to intensive care staff but will require future validation studies to assess its utility and potential prognostic implications.

A white light-emitting diode (0.33, 0.33) is fabricated using perovskite quantum dot/silica composites. It is shown to have greatly improved stability. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

The accumulation of leukocytes in inflamed tissue results from adhesive interactions between leukocytes and endothelial cells within the microcirculation. These adhesive interactions and the excessive filtration of fluid and protein that accompanies an inflammatory response are largely confined to one region of the microvasculature: postcapillary venules. The nature and magnitude of the leukocyte-endothelial cell adhesive interactions that take place within postcapillary venules are determined by a variety of factors, including expression of adhesion molecules on leukocytes and/or endothelial cells, products of leukocyte (superoxide) and endothelial cell (nitric oxide) activation, and the physical forces generated by the movement of blood along the vessel wall. The contribution of different adhesion molecules to leukocyte rolling, adherence, and emigration in venules is discussed. Emerging views on potential endogenous antiadhesion molecules produced by endothelial cells as well as the influence of alterations in shear rate on leukocyte adhesion are addressed. Finally, the pathophysiological significance of the microvascular responses to inflammation are discussed in terms of adhesion-directed strategies for the treatment of different cardiovascular diseases and circulatory disorders.

The basis of any service positioning strategy is the service itself, but marketing offers little guidance on how to craft service processes for positioning purposes. A new approach suggests that within service systems, structural process design can be used to “engineer” services on a more scientific, rational basis.

STUDY OBJECTIVES: To develop an archive of self-report questions assessing sleep disturbance and sleep-related impairments (SRI), to develop item banks from this archive, and to validate and calibrate the item banks using classic validation techniques and item response theory analyses in a sample of clinical and community participants. DESIGN: Cross-sectional self-report study. SETTING: Academic medical center and participant homes. PARTICIPANTS: One thousand nine hundred ninety-three adults recruited from an Internet polling sample and 259 adults recruited from medical, psychiatric, and sleep clinics. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: This study was part of PROMIS (Patient-Reported Outcomes Information System), a National Institutes of Health Roadmap initiative. Self-report item banks were developed through an iterative process of literature searches, collecting and sorting items, expert content review, qualitative patient research, and pilot testing. Internal consistency, convergent validity, and exploratory and confirmatory factor analysis were examined in the resulting item banks. Factor analyses identified 2 preliminary item banks, sleep disturbance and SRI. Item response theory analyses and expert content review narrowed the item banks to 27 and 16 items, respectively. Validity of the item banks was supported by moderate to high correlations with existing scales and by significant differences in sleep disturbance and SRI scores between participants with and without sleep disorders. CONCLUSIONS: The PROMIS sleep disturbance and SRI item banks have excellent measurement properties and may prove to be useful for assessing general aspects of sleep and SRI with various groups of patients and interventions.

In this lecture, evidence is presented to support the following hypothesis regarding the roles of xanthine oxidase-derived oxidants and granulocytes in ischemia-reperfusion-induced microvascular injury. During the ischemic period, ATP is catabolized to yield hypoxanthine. The hypoxic stress also triggers the conversion of NAD-reducing xanthine dehydrogenase to the oxygen radical-producing xanthine oxidase. During reperfusion, molecular oxygen is reintroduced into the tissue where it reacts with hypoxanthine and xanthine oxidase to produce a burst of superoxide anion and hydrogen peroxide. In the presence of iron, superoxide anion and hydrogen peroxide react via the Haber-Weiss reaction to form hydroxyl radicals. This highly reactive and cytotoxic radical then initiates lipid peroxidation of cell membrane components and the subsequent release of substances that attract, activate, and promote the adherence of granulocytes to microvascular endothelium. The adherent granulocytes then cause further endothelial cell injury via the release of superoxide and various proteases.

The mechanism(s) importing salt tolerance to plants remains unresolved. Although cotton ( Gossypium hirsutum L.) is classified as salt‐tolerant plant, variation in salt tolerance has been observed among different cultivars. The purpose of this study was to determine if more salt‐tolerant cultivars contain higher constitutive or inducible levels of antioxidants than more salt‐sensitive cultivars. Greenhouse‐grown salt‐tolerant (cv. Acaia 1517‐88 and Acala 1517‐SR2) and salt‐sensitive (cv. Deltapine 50 and Stoneville 825) cotton plants treated with either 0 or 150 m M NaCl were analyzed for differences in growth and antioxidant capocities. The 150 m M NaCl treatment resulted in more than 40% reduction in growth of Deltapine 50 and Stoneville 825 and less than 30% reduction in the Acala cultivars. The more salt‐tolerant cultivars had higher constitutive levels of catalase (121‐215%) and u‐tocopherol (312‐420%). The salt treatment resulted in a 38 to 72% increase in peroxidase activity and a 55 to 101% increase in glutathione reductase activity in the Acala cultivars while the activities of these enzymes remained constant or decreased in the more sensitive cultivars. The Acala cultivars also exhibited a lower oxidized/reduced ascorbic acid ratio and a higher reduced/oxidized glutathione ratio than the more sensitive cultivars when grown at 150 m M NaCl. When subjected to a one‐time salt treatment, lipid peroxidation in Deltapine 50 increased 51% over Acala 1517‐88. These data indicate that protection from oxidative damage by higher levels of antioxidants and a more active ascorbate‐glutathione cycle may be involved in tbe development of salt tolerance in cotton.

Findings from the National Cancer Institute's National Lung Screening Trial established that lung cancer mortality in specific high-risk groups can be reduced by annual screening with low-dose computed tomography. These findings indicate that the adoption of lung cancer screening could save many lives. Based on the results of the National Lung Screening Trial, the American Cancer Society is issuing an initial guideline for lung cancer screening. This guideline recommends that clinicians with access to high-volume, high-quality lung cancer screening and treatment centers should initiate a discussion about screening with apparently healthy patients aged 55 years to 74 years who have at least a 30-pack-year smoking history and who currently smoke or have quit within the past 15 years. A process of informed and shared decision-making with a clinician related to the potential benefits, limitations, and harms associated with screening for lung cancer with low-dose computed tomography should occur before any decision is made to initiate lung cancer screening. Smoking cessation counseling remains a high priority for clinical attention in discussions with current smokers, who should be informed of their continuing risk of lung cancer. Screening should not be viewed as an alternative to smoking cessation.

The relationship between diabetes, insulin and zinc (Zn) is complex with no clear cause and effect relationships. In Type 1 diabetes there is a lack of insulin production, in Type 2 diabetes resistance to the effects of insulin are predominant. Both Type 1 and Type 2 have the same long-term complications. Diabetes effects zinc homeostasis in many ways, although it is most probably the hyperglycemia, rather than any primary lesion related to diabetes, which is responsible for the increased urinary loss and decreases in total body zinc. The role of Zn deficiency, which could, at least potentially, exacerbate the cytokine-induced damage in the autoimmune attack which destroys the islet cell in Type 1 diabetes, is unclear. Since Zn plays a clear role in the synthesis, storage and secretion of insulin as well as conformational integrity of insulin in the hexameric form, the decreased Zn, which affects the ability of the islet cell to produce and secrete insulin, might then compound the problem, particularly in Type 2 diabetes. Several of the complications of diabetes may be related to increased intracellular oxidants and free radicals associated with decreases in intracellular Zn and in Zn dependent antioxidant enzymes. There appears to be a complex interrelationship between Zn and both Type 1 and Type 2 diabetes. The role of Zn in the clinical management of diabetes, its complications, or in its prevention is, at best, unclear.

Nitrite represents a circulating and tissue storage form of NO whose bioactivation is mediated by the enzymatic action of xanthine oxidoreductase, nonenzymatic disproportionation, and reduction by deoxyhemoglobin, myoglobin, and tissue heme proteins. Because the rate of NO generation from nitrite is linearly dependent on reductions in oxygen and pH levels, we hypothesized that nitrite would be reduced to NO in ischemic tissue and exert NO-dependent protective effects. Solutions of sodium nitrite were administered in the setting of hepatic and cardiac ischemia-reperfusion (I/R) injury in mice. In hepatic I/R, nitrite exerted profound dose-dependent protective effects on cellular necrosis and apoptosis, with highly significant protective effects observed at near-physiological nitrite concentrations. In myocardial I/R injury, nitrite reduced cardiac infarct size by 67%. Consistent with hypoxia-dependent nitrite bioactivation, nitrite was reduced to NO, S-nitrosothiols, N-nitros-amines, and iron-nitrosylated heme proteins within 1-30 minutes of reperfusion. Nitrite-mediated protection of both the liver and the heart was dependent on NO generation and independent of eNOS and heme oxygenase-1 enzyme activities. These results suggest that nitrite is a biological storage reserve of NO subserving a critical function in tissue protection from ischemic injury. These studies reveal an unexpected and novel therapy for diseases such as myocardial infarction, organ preservation and transplantation, and shock states.

Joel Brockner, Phyllis A. Siegel, Joseph P. Daly, Tom Tyler, Christopher Martin, When Trust Matters: The Moderating Effect of Outcome Favorability, Administrative Science Quarterly, Vol. 42, No. 3 (Sep., 1997), pp. 558-583

Erythrocytes of diabetic patients have abnormal membrane properties. We examined in vivo membrane lipid peroxidation in erythrocytes of diabetic subjects and its possible relationship with hyperglycemia. Lipid peroxidation was assessed in fresh, untreated erythrocytes by quantitating thiobarbituric acid reactivity and an adduct of phospholipids and malonyldialdehyde (MDA), an end product of lipid peroxidation, with thin-layer chromatography of lipid extract of diabetic erythrocytes. There was a significantly increased membrane lipid peroxidation in diabetic erythrocytes compared with nondiabetic erythrocytes. The degree of membrane lipid peroxidative damage in erythrocytes was significantly correlated with the level of glycosylated hemoglobin, an index of mean glucose level for the preceding 3-4 mo. This suggests that peroxidation of membrane lipids and accumulation of MDA occurs in erythrocytes of diabetic patients.

BACKGROUND: Venous thromboembolism (VTE) is a common source of perioperative morbidity and mortality. OBJECTIVE: These evidence-based guidelines from the American Society of Hematology (ASH) intend to support decision making about preventing VTE in patients undergoing surgery. METHODS: ASH formed a multidisciplinary guideline panel balanced to minimize bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline-development process, including performing systematic reviews. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment. RESULTS: The panel agreed on 30 recommendations, including for major surgery in general (n = 8), orthopedic surgery (n = 7), major general surgery (n = 3), major neurosurgical procedures (n = 2), urological surgery (n = 4), cardiac surgery and major vascular surgery (n = 2), major trauma (n = 2), and major gynecological surgery (n = 2). CONCLUSIONS: For patients undergoing major surgery in general, the panel made conditional recommendations for mechanical prophylaxis over no prophylaxis, for pneumatic compression prophylaxis over graduated compression stockings, and against inferior vena cava filters. In patients undergoing total hip or total knee arthroplasty, conditional recommendations included using either aspirin or anticoagulants, as well as for a direct oral anticoagulant over low-molecular-weight heparin (LMWH). For major general surgery, the panel suggested pharmacological prophylaxis over no prophylaxis, using LMWH or unfractionated heparin. For major neurosurgery, transurethral resection of the prostate, or radical prostatectomy, the panel suggested against pharmacological prophylaxis. For major trauma surgery or major gynecological surgery, the panel suggested pharmacological prophylaxis over no prophylaxis.

Health education materials, medical instructions, consent forms, and self-report questionnaires are often given to patients with little regard for their ability to read them. Reading ability is rarely tested in medical settings. The Rapid Estimate of Adult Literacy in Medicine (REALM) was developed as a quick screening tool to assist physicians in identifying patients with limited reading skills and in estimating patient reading levels. This information can be used to tailor materials and instructions to patients' abilities. The REALM and the reading sections of the Peabody Individual Achievement Test-Revised and the Slosson Oral Reading Test were used to test reading ability in 207 adults in six public and private primary care clinics. REALM scores correlated highly with those of the standardized reading tests. The REALM, which takes three to five minutes to administer and score, appears to be a practical instrument to estimate patient literacy in primary care, patient education, and medical research.