Serum α- and γ-tocopherol concentrations and risk of advanced beta cell autoimmunity in children with HLA-conferred susceptibility to type 1 diabetes mellitus

Aims/hypothesis The aim of our study was to assess the associations of serum α- and γ-tocopherol concentrations with the risk of advanced beta cell autoimmunity in children with HLA-conferred genetic susceptibility to type 1 diabetes mellitus. Methods A case–control study with 108 cases with advanced beta cell autoimmunity and 216 matched control participants nested within the birth cohort of the Type 1 Diabetes Prediction and Prevention Project. A serum sample for vitamin E analyses was collected from all the children in the cohort at the age of 1 year and thereafter at 12 month intervals. For each case–control group, all the repeated serum samples up to the age of seroconversion to autoantibody positivity in the case were analysed. A conditional logistic regression model was used to determine potential associations between seroconversion and serum tocopherol concentrations. Results Serum α- or γ-tocopherol concentrations were not significantly associated with the risk of advanced beta cell autoimmunity. The odds ratio (95% CI) for μmol/l increase in serum concentration of the first-year sample was 0.97 (0.92–1.03) for α-tocopherol and 1.10 (0.70–1.74) for γ-tocopherol. However, there was an interaction between high values of γ-tocopherol at the age of 1 year and the time of seroconversion (p = 0.024). Conclusions/interpretation It seems unlikely that high concentrations of α- or γ-tocopherol protect against advanced beta cell autoimmunity in young children.     

Quantitative Assessment of Myocardial Perfusion in the Detection of Significant Coronary Artery Disease : Cutoff Values and Diagnostic Accuracy of Quantitative [O]H2O PET Imaging

Background

Recent studies have demonstrated improved diagnostic accuracy for detecting coronary artery disease (CAD) when myocardial blood flow (MBF) is quantified in absolute terms, but there are no uniformly accepted cutoff values for hemodynamically significant CAD.

Objectives

The goal of this study was to determine cutoff values for absolute MBF and to evaluate the diagnostic accuracy of quantitative [¹⁵O]H₂O positron emission tomography (PET).

Methods

A total of 330 patients underwent both quantitative [¹⁵O]H₂O PET imaging and invasive coronary angiography in conjunction with fractional flow reserve measurements. A stenosis >90% and/or fractional flow reserve ≤0.80 was considered obstructive; a stenosis <30% and/or fractional flow reserve >0.80 was nonobstructive.

Results

Hemodynamically significant CAD was diagnosed in 116 (41%) of 281 patients who fulfilled study criteria for CAD. Resting perfusion was 1.00 ± 0.25 and 0.92 ± 0.23 ml/min/g in regions supplied by nonstenotic and significantly stenosed vessels, respectively (p < 0.001). During stress, perfusion increased to 3.26 ± 1.04 ml/min/g and 1.73 ± 0.67 ml/min/g, respectively (p < 0.001). The optimal cutoff values were 2.3 and 2.5 for hyperemic MBF and myocardial flow reserve, respectively. For MBF, these cutoff values showed a sensitivity, specificity, and accuracy for detecting significant CAD of 89%, 84%, and 86%, respectively, at a per-patient level and 87%, 85%, and 85% at a per-vessel level. The corresponding myocardial flow reserve values were 86%, 72%, and 78% (per patient) and 80%, 82%, and 81% (per vessel). Age and sex significantly affected diagnostic accuracy of quantitative PET.

Conclusions

Quantitative MBF measurements with the use of [¹⁵O]H₂O PET provided high diagnostic performance, but both sex and age should be taken into account.     

Adherence of hip and knee arthroplasty studies to RSA standardization guidelines: A systematic review

Background and purpose

Guidelines for standardization of radiostereometry (RSA) of implants were published in 2005 to facilitate comparison of outcomes between various research groups. In this systematic review, we determined how well studies have adhered to these guidelines.

Methods

We carried out a literature search to identify all articles published between January 2000 and December 2011 that used RSA in the evaluation of hip or knee prosthesis migration. 2 investigators independently evaluated each of the studies for adherence to the 13 individual guideline items. Since some of the 13 points included more than 1 criterion, studies were assessed on whether each point was fully met, partially met, or not met.

Results

153 studies that met our inclusion criteria were identified. 61 of these were published before the guidelines were introduced (2000–2005) and 92 after the guidelines were introduced (2006–2011). The methodological quality of RSA studies clearly improved from 2000 to 2011. None of the studies fully met all 13 guidelines. Nearly half (43) of the studies published after the guidelines demonstrated a high methodological quality and adhered at least partially to 10 of the 13 guidelines, whereas less than one-fifth (11) of the studies published before the guidelines had the same methodological quality. Commonly unaddressed guideline items were related to imaging methodology, determination of precision from double examinations, and also mean error of rigid-body fitting and condition number cutoff levels.

Interpretation

The guidelines have improved methodological reporting in RSA studies, but adherence to these guidelines is still relatively low. There is a need to update and clarify the guidelines for clinical hip and knee arthroplasty RSA studies.Since the introduction of radiostereometry (RSA) in 1974, the method has continuously proven to be a valuable tool in the assessment of migration following hip and knee arthroplasty. Although the importance of a stepwise introduction of new orthopedic implants was presented in 1995 (Malchau 1995), only recently has it been fully acknowledged that deletion of some of these crucial steps can have catastrophic consequences (Kärrholm 2012). The phased or stepwise introduction process is based on the hypothesis that a more precise and careful evaluation of new implants will reduce the number of patients at risk of unexpected failures. There are 4 suggested steps to this process (Malchau 1995). The initial step involves preclinical implant testing. After this, the first clinical step consists of prospective randomized studies that use RSA. The second clinical step involves multicenter studies and the final step is composed of registry studies.The detection of early migration or accelerated wear using RSA are ways of predicting early implant failure, and are therefore important components of this stepwise introduction process (Kärrholm 2012). Although RSA would probably not have been able to forecast some of the problems related to the metal-on-metal articulation, it could have prevented the premature introduction of Boneloc cement. When Boneloc was introduced, the Norwegian Arthroplasty Register needed more than 1,000 patients before it could be proven to be an inferior cement based on a higher revision rate compared to regular bone cement (Havelin et al. 1995). Using RSA only, 30 patients were included in a study that—already after 6 months—showed that Boneloc-cemented implants were clearly less stable than those with conventional bone cement (Thanner et al. 1995). If Boneloc had been studied with RSA prior to being released onto the market, thousands of patients would have been spared from early revision. There are several other examples of poor orthopedic implants or materials that should have been tested with RSA prior to widespread release (Muirhead-Allwood 1998, Norton et al. 2002). In the past, many serious problems initially manifested as low-incidence events but only later proved to be the tip of the iceberg (Malchau et al. 2011). Despite the fact that the algorithm for introduction of new implant designs was established more than 15 years ago, many new and untested implants still appear on the market. The orthopedic community has acknowledged that the fast spread of undocumented new implants is no longer acceptable (Kärrholm 2012).With the increasing importance of RSA, it has also been recognized that reporting of RSA outcomes should be standardized. The guidelines for standardization of radiostereometry of implants were published in August 2005, to facilitate comparison of RSA outcomes reported from different centers (Valstar et al. 2005). In that paper, an appendix of 13 main items that should be used to account for the results of a clinical RSA study is outlined. Furthermore, since RSA is a highly technical method, the reliability and reproducibility of a study can only be assessed when all standardized output items have been adequately addressed.We investigated whether the RSA guidelines have resulted in improved methodological reporting in clinical RSA studies of hip and knee arthroplasty. We also assessed the overall level of adherence to each of the individual guidelines following their introduction.     

Body mass index and health-related quality of life in apparently healthy individuals

Purpose

Obesity is known to be associated with a range of chronic medical comorbidities, but little is known about the impact of overweight and obesity on health-related quality of life (HRQoL) in persons without chronic diseases. The aim of this study was to assess HRQoL, body mass index (BMI) and health behavior patterns in a community sample of subjects who had no long-lasting medical comorbidities

Methods

We assessed HRQoL in 1,187 apparently healthy individuals (mean age 57 ± 7 years), of whom 24 % were classified as normal weight, 49 % as overweight, 20 % as obese and 7 % as very obese. Two different instruments of HRQoL were used: the generic Short-Form Health Survey (SF-36) questionnaire and the preference-based instrument EuroQol (EQ-5D).

Results

All physical components of the SF-36 decreased linearly according to BMI categories in women. In men, only poorer physical functioning scale showed linearity with rising BMI. Scores on the mental components of the SF-36 did not differ by BMI categories in either gender. The EQ-5D index and EuroQol visual analogue scale scores decreased linearly with rising BMI only in women.

Conclusions

In apparently healthy middle-aged subjects, physical HRQoL decreases with increasing level of BMI and more so in women than in men. Mental components of HRQoL do not differ between the categories of BMI in either gender.     

Modeling the cardiac indices of stress and performance of nuclear power plant operators during simulated fault scenarios

Acute stress can affect cognitive processing and decrease performance in demanding, stressful situations. Here, we recorded the cardiac indices of stress, that is, the heart rate and heart rate variability together with the physical activity of nuclear power plant operators, and examined their association with crew performance, while the operator crews were managing simulated incident and accident situations. Crew performance was evaluated both by the operator instructor and as the time taken to resolve the situation. In total, 64% of the variance in the information-seeking performance (adj-R² = .64, p < .01), and 41% of variation in the performance time (adj-R² = .41, p < .01) were explained by the psychophysiology. The cardiac measures indicated that increased stress was associated with poorer information-seeking performance and longer performance time. Increased physical activity was associated with poorer information seeking only. Otherwise, crew performance was robust, as the diagnosis and corrective actions, use of emergency operations procedures, and collaboration, were only weakly associated with the stress physiology. The association between information-seeking performance and stress might be explained by the larger requirement for cognitive processing at the information-gathering phase of the task. The results of the study show that psychophysiological measurements of stress and activity can provide valuable information on stress and its association with cognitive performance at work.     

H-ras oncogene point mutations in arthritic synovium

Objective. To examine mutational activation of ras proto-oncogenes in synovial tissue from patients with rheumatoid arthritis (RA) compared with synovial specimens from patients with osteoarthritis (OA) or other arthropathies. Synovial samples from cadavers, without any signs of joint disease, were used as control material. Methods. Using a combination of polymerase chain reaction (PCR) and automated sequencing of the amplified PCR product, regions around codons 12, 13, and 61 of the H-, K-, and N-ras proto-oncogenes were analyzed. Confirmation of mutations was based on restriction fragment length polymorphism analysis and/or oligonucleotide hybridization. Results. Four (6%) of 72 patients with RA, 2 (13%) of 16 with OA, and 1 (8%) of 12 with other arthropathies harbored mutant H-ras proto-oncogenes, and were heterozygous at codon 13 for the GGT→GAT (Gly→Asp) change. An unexpected mutation was found in the H-ras gene, in which a heterozygous GTG→ATG (Val→Met) mutation was observed over codon 14. The incidence for this mutation was 39% (28 of 72) in RA patients, 94% (15 of 16) in OA patients, and 42% (5 of 12) in patients with other arthropathies. All samples carrying the codon 13 mutation of H-ras were also codon 14-mutated, i.e., double mutations existed. Identical point mutations were also detected in a few synovial specimens obtained from cadavers (n = 8), including a single case of double mutation. All specimens showed normal K- and N-ras loci. Conclusion. Activation of proto-oncogene H-ras by point mutation in codons 13 and 14 occurred in the synovial tissue of patients with RA, OA, or other arthropathies, as well as, to some extent, in the control synovia, indicating that the phenomenon is not specific for RA. In codon 14, incidence of the H-ras point mutation was highest in OA tissue. The possible significance of this codon 14-mutated H-ras gene needs to be clarified.