A comparison of the reproducibility and the sensitivity to change of visual analogue scales, Borg scales, and Likert scales in normal subjects during submaximal exercise

OBJECTIVE: To assess which subjective scale, the visual analogue scale (VAS), the Borg CR10 (Borg) scale, or the Likert scale (LS), if any, is decidedly more reproducible and sensitive to change in the assessment of symptoms. DESIGN: Prospective clinical study. SETTING: Exercise laboratory. PARTICIPANTS: Twenty-three physically active male subjects (mean +/- SD age of 30 +/- 4 years old) were recruited. INTERVENTION: Each subject attended the exercise laboratory on four occasions at intervals of 1 week. Three subjective scales were used: (1) the VAS (continuous scale); (2) the Borg scale (12 fixed points); and (3) the Likert scale (LS; 5 fixed points). Four identical submaximal tests were given (2 min at 60% maximum oxygen uptake [VO(2)max] and 6 min at 70% VO(2)max). Two tests were undertaken to assess the reproducibility of scores that were obtained with each subjective scale. Two other tests were undertaken to assess the sensitivity of each scale to a change in symptom perception: a double-blind treatment with propranolol, 80 mg, (ie, active therapy; to increase the sensation of breathlessness and general fatigue during exercise) or matching placebo. The subjective scale scores were measured at 1 min 30 s, 5 min 30 s, and 7 min 15 s of exercise. Reproducibility was defined as the proportion of total variance (ie, between-subject plus within-subject variance) explained by the between-subject variance given as a percentage. Sensitivity was defined as the effect of the active drug therapy over the variation within subjects. RESULTS: Overall, the VAS performed best in terms of reproducibility for breathlessness and general fatigue, with reproducibility coefficients as high as 78%. For sensitivity, the VAS was best for breathlessness (ratio, 2.7) and the Borg scale was most sensitive for general fatigue (ratio, 3.0). The relationships between the respective psychological and physiologic variables were reasonably stable throughout the testing procedure, with overall typical correlations of 0.73 to 0.82 CONCLUSION: This study suggests that subjective scales can reproducibly measure symptoms during steady-state exercise and can detect the effect of a drug intervention. The VAS and Borg scales appear to be the best subjective scales for this purpose.     

A common variation in deiodinase 1 gene DIO1 is associated with the relative levels of free thyroxine and triiodothyronine

INTRODUCTION: Genetic factors influence circulating thyroid hormone levels, but the common gene variants involved have not been conclusively identified. The genes encoding the iodothyronine deiodinases are good candidates because they alter the balance of thyroid hormones. We aimed to thoroughly examine the role of common variation across the three deiodinase genes in relation to thyroid hormones. METHODS: We used HapMap data to select single-nucleotide polymorphisms (SNPs) that captured a large proportion of the common genetic variation across the three deiodinase genes. We analyzed these initially in a cohort of 552 people on T(4) replacement. Suggestive findings were taken forward into three additional studies in people not on T(4) (total n = 2513) and metaanalyzed for confirmation. RESULTS: A SNP in the DIO1 gene, rs2235544, was associated with the free T(3) to free T(4) ratio with genome-wide levels of significance (P = 3.6 x 10(-13)). The C-allele of this SNP was associated with increased deiodinase 1 (D1) function with resulting increase in free T(3)/T(4) ratio and free T(3) and decrease in free T(4) and rT(3). There was no effect on serum TSH levels. None of the SNPs in the genes coding for D2 or D3 had any influence on hormone levels. CONCLUSIONS: This study provides convincing evidence that common genetic variation in DIO1 alters deiodinase function, resulting in an alteration in the balance of circulating free T(3) to free T(4). This should prove a valuable tool to assess the relative effects of circulating free T(3) vs. free T(4) on a wide range of biological parameters.     

Lipids and CVD management: towards a global consensus.

Cardiovascular disease (CVD) is currently the leading cause of morbidity and mortality worldwide and its incidence is likely to increase. Multiple risk factors contribute to CVD. Elevated LDL-cholesterol (LDL-C) and triglyceride levels, low HDL-cholesterol levels, hypertension, type 2 diabetes, and smoking are key modifiable risk factors. Such risk factors are present in 80-90% of coronary heart disease (CHD) patients. For many factors, modification can significantly reduce CVD incidence. For example, statin-induced LDL-C reductions reduce cardiovascular events by 24-37% and smoking cessation reduces CHD mortality by 36%. The need to identify and treat these risk factors has led many national and local groups to develop clinical practice guidelines for management of CVD. Although the aim of such guidelines is to provide practitioners with a framework to identify, prioritize, and manage patients, the plethora of guidelines can cause confusion. In addition, research indicates that guidelines are not being optimally implemented. This review considers these practical issues, highlights the common goals shared by many guidelines, and focuses on how these can be best achieved. It also highlights areas where the guidelines differ and discusses points to consider when selecting the most appropriate recommendation.     

Efficient T cell repertoire selection in tetraparental chimeric mice independent of thymic epithelial MHC

Nonthymic epithelial cells were compared with thymic epithelial cells for their role in T cell repertoire selection. Tetraparental aggregation chimeras were generated from T and B cell-deficient mice (H-2(d) SCID or H-2(b) Rag-/-) and thymus-deficient nude mice (H-2(b) or H-2(d)). These tetraparental mice showed primary protective CD8(+) T cell responses, after lymphocytic choriomeningitis virus infection, that were peptide-specifically restricted to either thymic or nonthymic epithelial MHC at comparable levels. These chimeras also mounted neutralizing IgG responses dependent on cognate CD4(+) T helper cell activity restricted to nonthymic epithelial MHC. Therefore, in contrast to earlier results with irradiation or thymus chimeras, these relatively undisturbed tetraparental mice reveal that the MHC of nonthymic epithelial cells efficiently selects a functional T cell repertoire.     

Melanoma cells resistant to inhibition of growth by melanocyte stimulating hormone.

Melanocyte stimulating hormone (MSH) enhances melanization but inhibits proliferation of Cloudman S91 melanoma cells in culture. We have isolated variants of these cells that can grow in the presence of MSH. The conclusions we have reached from analyses of these cells are the following: (1) Basal tyrosinase activity (monophenol monooxygenase; monophenol, dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1), i.e., the activity that is present in the absence of added MSH, is related through a common biochemical pathway to MSH-mediated control of growth. (2) MSH-inducible tyrosinase activity does not appear to be related to MSH control of growth. (3) The morphological changes that occur following the addition of MSH or cAMP are related to controls of growth and not to those of melanization.     

Intravascular Coagulation Activation in a Murine Model of Thrombomodulin Deficiency: Effects of Lesion Size, Age, and Hypoxia on Fibrin Deposition

We consecutively inactivated both alleles of the thrombomodulin (TM)gene in murine embryonic stem (ES) cells and generated TM-deficient(TM^/) chimeric mice. Quantitation of an ES-cellmarker and protein C cofactor activity indicates that up to 50% ofpulmonary endothelial cells are ES-cell derived and therefore TMdeficient. Infusions of ¹²⁵I-fibrinogen into mice show asignificant increase (fourfold, P < .005) in radiolabeledcross-linked fibrin in TM^/ chimeric mouse lung ascompared with wild-type mice. However, only chimeric mice that exhibitat least a 30% reduction in protein C cofactor activity and are atleast 15 months old display this phenotype. Immunocytochemicallocalization of TM in chimeras shows a mosaic pattern of expression inboth large and small blood vessels. Colocalization of cross-linkedfibrin and neo (used to replace TM) reveals that fibrin is deposited inTM^/ regions. However, the fibrin deposits werelargely restricted to pulmonary vessels with a lumenal area greaterthan 100 µm². The hypercoagulable phenotype can beinduced in younger chimeric mice by exposure to hypoxia, which causes afivefold increase in -fibrin levels in lung. Our findings show thatTM chimerism results in spontaneous, intravascular fibrin depositionthat is dependent on age and the magnitude of the TM deficiency.     

Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation

Multicolor nonlinear microscopy of living tissue using two- and three-photon-excited intrinsic fluorescence combined with second harmonic generation by supermolecular structures produces images with the resolution and detail of standard histology without the use of exogenous stains. Imaging of intrinsic indicators within tissue, such as nicotinamide adenine dinucleotide, retinol, indoleamines, and collagen provides crucial information for physiology and pathology. The efficient application of multiphoton microscopy to intrinsic imaging requires knowledge of the nonlinear optical properties of specific cell and tissue components. Here we compile and demonstrate applications involving a range of intrinsic molecules and molecular assemblies that enable direct visualization of tissue morphology, cell metabolism, and disease states such as Alzheimer's disease and cancer.     

Control of leukocyte rolling velocity in TNF-alpha-induced inflammation by LFA-1 and Mac-1.

Previously it was shown that beta(2)-integrins are necessary for slow leukocyte rolling in inflamed venules. In this study, mice that are deficient for either one of the beta(2)-integrins, alpha(L)beta(2) (LFA-1) or alpha(M)beta(2) (Mac-1), were used to determine which of the beta(2)-integrins are responsible for slowing rolling leukocytes. The cremaster muscles of these mice were treated with tumor necrosis factor-alpha and prepared for intravital microscopy. The average rolling velocities in venules were elevated in LFA-1(-/-) mice (11.0 +/- 0.7 microm/s) and Mac-1(-/-) mice (10.1 +/- 1.1 microm/s) compared to wild-type mice (4.8 +/- 0.3 microm/s; P <.05), but were lower than in CD18(-/-) mice (28.5 +/- 2.1 microm/s). When both LFA-1 and Mac-1 were absent or blocked, rolling velocity became dependent on shear rate and approached that of CD18(-/-) mice. In addition, leukocyte adhesion efficiency was decreased in LFA-1(-/-) mice to near CD18(-/-) levels, but decreased only slightly in Mac-1(-/-) mice. Thus, both LFA-1 and Mac-1 contribute to slowing down rolling leukocytes, although LFA-1 is more important than Mac-1 in efficiently inducing firm adhesion.     

A nosocomial outbreak of community-associated methicillin-resistant Staphylococcus aureus among healthy newborns and postpartum mothers

BACKGROUND: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has increasingly been isolated from individuals with no predisposing risk factors; however, such strains have rarely been linked to outbreaks in the hospital setting. The present study describes the investigation of an outbreak of CA-MRSA that occurred in the maternal-newborn unit of a large community teaching hospital in Toronto, Ontario. METHODS: Screening and clinical specimens collected from mothers and newborns delivered during the outbreak period, as well as from staff on the affected unit, were submitted for microbiological testing. Computerized delivery logs and nursing notes were reviewed, and a case control study was conducted. RESULTS: Analysis by pulsed-field gel electrophoresis revealed 38 babies and seven mothers with MRSA colonization and/or infection by the same unique strain (Canadian MRSA-10-related) from September to December 2004. Isolates were characterized as having the staphylococcal chromosome cassette mec type IVa and were positive for the Panton-Valentine leukocidin gene. No one health care worker was associated with all cases; however, mothers and newborns exposed to one particular nurse (Nurse A) were almost 23 times (odds ratio 22.7, 95% CI 3.3 to 195.9) more likely to acquire MRSA than those with no such contact. MRSA was successfully isolated from Nurse A and from an environmental swab of a telephone recently used by Nurse A; both isolates matched the pulsed-field gel electrophoresis pattern of the outbreak strain. CONCLUSION: The first nosocomial outbreak of CA-MRSA among healthy newborns and postpartum mothers in Canada is described. Effective control of sustained MRSA transmission within an institution may require prompt identification, treatment and monitoring of colonized and/or infected staff.