Statin Use in Relation to Intraocular Pressure,Glaucoma, and Ocular Coherence Tomography Parameters in the UK Biobank

PurposeThe purpose of this study was to evaluate the relationship between statin use and glaucoma-related traits.MethodsIn a cross-sectional study, we included 118,153 UK Biobank participants with data on statin use and corneal-compensated IOP. In addition, we included 192,283 participants (8982 cases) with data on glaucoma status. After excluding participants with neurodegenerative diseases, 41,638 participants with macular retinal nerve fiber layer thickness (mRNFL) and 41,547 participants with macular ganglion cell inner plexiform layer thickness (mGCIPL) were available for analysis. We examined associations of statin use with IOP, mRNFL, mGCIPL, and glaucoma status utilizing multivariable-adjusted regression models. We assessed whether a glaucoma polygenic risk score (PRS) modified associations. We performed Mendelian randomization (MR) experiments to investigate associations with various glaucoma-related outcomes.ResultsStatin users had higher unadjusted mean IOP ± SD than nonusers, but in a multivariable-adjusted model, IOP did not differ by statin use (difference = 0.05 mm Hg, 95% confidence interval [CI] = −0.02 to 0.13, P = 0.17). Similarly, statin use was not associated with prevalent glaucoma (odds ratio [OR] = 1.05, 95% CI = 0.98 to 1.13). Statin use was weakly associated with thinner mRNFL (difference = −0.15 microns, 95% CI = −0.28 to −0.01, P = 0.03) but not with mGCIPL thickness (difference = −0.12 microns, 95% CI = −0.29 to 0.05, P = 0.17). No association was modified by the glaucoma PRS (P_interaction ≥ 0.16). MR experiments showed no evidence for a causal association between the cholesterol-altering effect of statins and several glaucoma traits (inverse weighted variance P ≥ 0.14).ConclusionsWe found no evidence of a protective association between statin use and glaucoma or related traits after adjusting for key confounders.     

Expression of pertussis toxin adenosine diphosphate-ribosyltransferase in a T-cell hybridoma reduces metastatic capacity

T-cell hybridomas are highly metastatic, and their in vitro invasiveness correlates with metastatic capacity. Invasion is blocked by pertussis toxin (PT), which adenosine diphosphate (ADP)-ribosylates G1-proteins, and we have provided evidence that the PT-sensitive signal stimulates leukocyte function-associated antigen-1 (LFA-1)-mediated adhesion required for invasion. PT pretreatment of TAM2D2 T-cell hybridoma cells reduced metastasis, but only to a limited extent. In the present study, we have transfected the cDNA of the PT ADP- ribosyltransferase S1 subunit into TAM2D2 cells to abrogate G1-protein function permanently. We report here a substantial reduction in the metastatic capacity of two transfectants, S05 and S09, in which 88% and 95% of the G1-proteins was ADP-ribosylated. Two-thirds of the mice injected with S09 cells were tumor-free. Metastasis to the liver was almost completely prevented and less metastases were formed in the spleen and kidneys. Metastasis formation by S05 cells in liver and spleen was much reduced, but in lymph nodes and peritoneal tissues, metastases occurred with a frequency similar to that of controls. We conclude that G1-proteins play an important role in T-cell hybridoma metastasis. We propose that the reduction in metastasis is due to diminished entry of tumor cells from the blood into tissues.     

Increased urinary nitric oxide oxidation products in children with active coeliac disease

BACKGROUND: Nitric oxide (NO) production catalyzed by iNOS (inducible NO synthase) is thought to take place mainly in macrophages after activation by inflammatory mediators. NO is subsequently oxidized to nitrite and nitrate, which are excreted in urine. The concentration of inflammatory mediators in small bowel biopsy specimens from patients with coeliac disease is increased. The latter could induce increased NO production by stimulation of intestinal macrophage iNOS, resulting in high levels of urinary NO oxidation products, nitrite and nitrate (NOx). AIM: In the present study we evaluated the urinary NOx/creatinine ratios in children with active coeliac disease (n = 22), coeliac disease patients on a gluten-free diet (n = 9), healthy (n = 11) and sick control children (n = 18). METHODS: The Griess reagent method was used for measuring urinary NOx. RESULTS: Median NOx/creatinine ratios of active coeliac disease patients, coeliac disease patients on a gluten-free diet, healthy and sick control patients were 1.21, 0.19, 0.10 and 0.13 mmol/mmol, respectively. All active coeliac disease patients showed increased NOx/ creatinine ratios. Urinary NOx/creatinine ratios of the active coeliac disease patients were significantly higher than those of healthy controls (p < 0.0001), sick controls (p < 0.0001) and coeliac disease patients on a gluten-free diet (p < 0.0001). CONCLUSION: The urinary NOx/creatinine ratio is increased in patients with active coeliac disease and reverts to normal on a gluten-free diet.     

Understanding and Addressing Barriers to Implementation of Environmental and Policy Interventions to Support Physical Activity and Healthy Eating in Rural Communities

Purpose: Rural residents are at greater risk of obesity than urban and suburban residents. Failure to meet physical activity and healthy eating recommendations play a role. Emerging evidence shows the effectiveness of environmental and policy interventions to promote physical activity and healthy eating. Yet most of the evidence comes from urban and suburban communities. The objectives of this study were to (1) identify types of environmental and policy interventions being implemented in rural communities to promote physical activity or healthy eating, (2) identify barriers to the implementation of environmental or policy interventions, and (3) identify strategies rural communities have employed to overcome these barriers. Methods: Key informant interviews with public health professionals working in rural areas in the United States were conducted in 2010. A purposive sample included 15 practitioners engaged in planning, implementing, or evaluating environmental or policy interventions to promote physical activity or healthy eating. Findings: Our findings reveal that barriers in rural communities include cultural differences, population size, limited human capital, and difficulty demonstrating the connection between social and economic policy and health outcomes. Key informants identified a number of strategies to overcome these barriers such as developing broad‐based partnerships and building on the existing infrastructure. Conclusion: Recent evidence suggests that environmental and policy interventions have potential to promote physical activity and healthy eating at the population level. To realize positive outcomes, it is important to provide opportunities to implement these types of interventions and document their effectiveness in rural communities.     

MHC5 The EuroQol in Parkinson''s Disease Research: Rated Current Health vs. Population-Derived Health State Preferences

The EuroQoL EQ-5D and MOS SF-36 are two generic quality of life measures that differ significantly in their design (the former being an index and the latter a profile). Both have been extensively used in evaluating interventions in acute disease. This study tested their comparative performance in a survey of patients with relapsing-remitting multiple sclerosis (MS).
METHODS: 309 patients with diagnosed relapsing-remitting MS were identified through the records of 5 specialist centers in North West England. Patients were contacted by telephone by a specialist MS nurse and asked to complete a set of questionnaires distributed by mail. The questionnaire booklet reproduced the English version of SF-36, together with the EQ-5D and a self completion form of the Barthel. Minimal additional background information was obtained from all respondents; 4 weeks following their completion of the initial booklet, a second identical booklet was sent to the first 200 initial respondents. Patients in this re-test sub-group were asked whether their health status had improved, deteriorated, or remained unchanged over the intervening period.
RESULTS: Of the 200 patients in the test/re-test subgroup, 144 (72%) replied on both occasions. Paired t-tests for the PCS, MCS, and general health perception scores on the SF-36 failed to generate comprehensive evidence of reliability. The weighted index form of the EQ-5D and the visual analogue scale self-ratings provided superior evidence of reliability. Standardized response means for both measures confirmed this general pattern.
CONCLUSION: EQ-5D performs satisfactorily as a generic measure of health-related quality of life in patients with MS.     

Summary of historical beryllium uses and airborne concentration levels at Los Alamos National Laboratory

Beryllium operations and accompanying medical surveillance of workers at Los Alamos National Laboratory began in the 1940s. In 1999 a Former Workers Medical Surveillance Program that includes screening for chronic beryllium disease was initiated. As part of this program, historical beryllium exposure conditions were reconstructed from archived paper and electronic industrial hygiene data sources to improve understanding of past beryllium uses and airborne concentration levels. Archived industrial hygiene sampling reports indicated beryllium was principally used in technical areas-01 and -03, primarily being machined. Beryllium was also used at 15 other technical areas in activities that ranged from explosives detonation to the manufacture of X-ray windows. A total of 4528 personal breathing zone and area air samples for beryllium, combined for purposes of calculating summary statistics, were identified during the records review phase. The geometric mean airborne beryllium concentration for the period 1949-1989 for all technical areas was 0.04 microg Be/m(3) with 97 percent of all sample below the 2.0 microg Be/m(3) occupational exposure limit (OEL). Average beryllium concentrations per decade were less than 1 microg Be/m(3) and annual geometric mean concentrations in technical area-03, the largest user of beryllium, were generally below 0.1 microg Be/m(3), indicating exposure was generally well-controlled, that is, below the OEL. Typical of many retrospective exposure assessments, not all archived data could be extracted and summarized. Despite this, we report a reasonable summary of potential beryllium uses and airborne concentration levels a worker may have encountered from 1949-1989. These data can be used to more effectively identify former worker populations at potential risk for chronic beryllium disease and to offer these workers screening as part of the Former Worker Medical Surveillance Program, and in the event that a case is diagnosed, help to understand historical exposure conditions.     

Excretory urography with iohexol: evaluation in children

A multicenter clinical study was conducted using iohexol, a second-generation nonionic contrast medium, for excretory urography performed in 130 children. Doses of iohexol (300 mg iodine/ml) ranged between 150 and 660 mgI/kg (0.5 and 2.2 ml/kg). Iohexol was tolerated well, and no significant adverse reactions occurred. Sixty-five iohexol urograms were evaluated to determine the minimum dose for adequate visualization of the kidneys and collecting systems. A dose greater than 300 mgI/kg (1.0 ml/kg) always resulted in a urogram of diagnostic quality, while visualization was insufficient for diagnosis in 10% of studies done with doses of 150-300 mgI/kg (0.5-1.0 ml/kg). Another 65 iohexol urograms were compared in a blinded manner with a similar number of studies performed using iothalamate meglumine at comparable iodine concentration and dose. Visualization of calyces and pelvoinfundibular structures achieved with iohexol was rated better with statistical significance, but there was no difference in visualization of the renal parenchyma or ureters. Use of iohexol in excretory urography may be advantageous in children who are at greatest risk for an adverse reaction to contrast media or in those most likely to benefit from use of a low osmolality contrast agent.     

Myocardial tagging in polar coordinates with use of striped tags

Regional deformation abnormalities in the heart wall provide a good indicator of ischemia. Myocardial tagging with magnetic resonance imaging is a new method of assessing heart wall motion during contraction. Current methods of myocardial tagging either do not provide two-dimensional information or lack a coordinate system well adapted to the morphology of the heart. In this article, the authors describe a new tagging method that provides a true polar coordinate system, with both radial and angular dimensions. This is accomplished with use of a section-selective version of spatially modulated magnetization resulting in striped tags (STAGs). These STAG planes are placed in the myocardium in a star pattern so that they intersect on the long axis of the heart and stripes appear through the width of the heart wall. In the short-axis view during contraction, rotation around the long axis yields angular information such as shear and twist, while separation of the stripes within the myocardium permits measurement of radial thickening. Therefore, this method provides a coordinate system for calculating two-dimensional strain that is adapted to the morphology of the left ventricle.     

The sensitivity and specificity of the immediate-spin crossmatch

The immediate-spin (IS) crossmatch is used to detect ABO incompatibility between donor red cells (RBCs) and the serum of the intended recipient. However, this test may be positive in the absence of ABO incompatibility (false positive) or it may be negative when ABO incompatibility exists (false negative). During a 25-month study, the rates of both false-positive and false-negative IS crossmatch results were evaluated, and the sensitivity and specificity of the IS crossmatch were determined. During the study period, 53,656 IS crossmatches were performed for patients without significant RBC antibodies. Fifty-five patients had positive IS crossmatches, and no false-negative reactions were found. In tests of 55 patients with positive IS crossmatches, 77 false-positive and 5 true-positive reactions were noted. The causes of the false-positive reactions were rouleaux (36 patients), cold-reactive antibodies (8 patients), a combination of rouleaux and cold-reactive antibodies (2 patients), fibrin clot (1 patient), and undetermined (3 patients). The sensitivity and specificity of the IS crossmatch were 100 and 99.86 percent, respectively. Laboratory personnel should be aware that the IS crossmatch may have false-positive or false-negative results, and they should develop written protocols to distinguish quickly between true-positive and false-positive reactions.