Which antigen to use in the detection of rheumatoid factors? Comparison of patients with rheumatoid arthritis and subjects with 'false positive' rheumatoid factor reactions

In the search for differences between rheumatoid factors (RF) in patients with rheumatoid arthritis (RA) and in non-rheumatoid subjects, the reactivity of IgM- and IgA-class RF with rabbit IgG (rIgG) and Fc fragments of rabbit and human IgG (rFc, hFc) was studied by enzyme immunoassay. From a community-based cohort (n = 7124) representing the adult population of Finland, RA patients (n = 130), other subjects positive in the Waaler-Rose (WaRo, sensitized sheep cell agglutination) test (n = 137), and controls matched for age, sex and living area were selected for further study. In RA sera there was a good correlation between the results in the WaRo test and in the IgM-RF ELISA (rIgG, rFc and hFc). A considerable number of 'false positive' sera, though positive in the WaRo test and the rIgG-ELISA, were negative in the rFc-ELISA. Twenty-two per cent of the false positive sera reacted with either hFc or rFc, both types being equally common. IgA-RF reacted more frequently with hFc than with rFc in both the RA and the 'false positive' sera. In some sera, IgM- and IgA-RFs reacted differently with human and rabbit Fc, e.g. IgM-RF reacted only with human Fc, and IgA-RF reacted with both hFc and rFc, thus suggesting different regulation of their formation.     

Association testing of variants in the hepatocyte nuclear factor 4alpha gene with risk of type 2 diabetes in 7,883 people

Two recent publications reported association of common polymorphisms in the P2 promoter of hepatocyte nuclear factor 4alpha (HNF4alpha) (the MODY1 gene) with risk for type 2 diabetes. We attempted to reproduce this putative association by genotyping 11 single nucleotide polymorphism (SNPs) spanning the HNF4alpha coding region and the P2 promoter in >3,400 patients and control subjects from Sweden, Finland, and Canada. One SNP that was consistently associated in the two previous reports (rs1884613, in the P2 promoter region) also trended in the same direction in our sample, albeit with a lower estimated odds ratio (OR) of 1.11 (P = 0.05, one-tailed). We genotyped this SNP (rs1884613) in an additional 4,400 subjects from North America and Poland. In this sample, the association was not confirmed and trended in the opposite direction (OR 0.88). Meta-analysis of our combined sample of 7,883 people (three times larger than the two initial reports combined) yielded an OR of 0.97 (P = 0.27). Finally, we provide an updated analysis of haplotype structure in the region to guide any further investigation of common variation in HNF4alpha. Although our combined results fail to replicate the previously reported association of common variants in HNF4alpha with risk for type 2 diabetes, we cannot exclude an effect smaller than that originally proposed, heterogeneity among samples, variation in as-yet-unmeasured genotypic or environmental modifiers, or true association secondary to linkage disequilibrium (LD) with as-yet-undiscovered variant(s) in the region.     

Occupational exposure of non-smoking restaurant personnel to environmental tobacco smoke in Finland

BACKGROUND: Environmental tobacco smoke (ETS) exposure levels in different restaurant types in Finland were assessed before the National Tobacco Act restricting smoking in restaurants was activated. METHODS: Exposure to ETS was determined by measuring nicotine in the breathing zone of non-smoking restaurant workers and by quantification of the nicotine metabolites cotinine and 3-hydroxycotinine in the urine of these workers during one whole work week. Altogether 23 workers from 15 restaurants were included in the study. RESULTS: The geometric mean (GM) breathing-zone nicotine level was 3.9 microg/m(3) (3.7 microg/m(3) in pubs, 1.4 microg/m(3) in dining restaurants, and 10.2 microg/m(3) in nightclubs). The GM cotinine and trans-3'-hydroxycotinine level in urine were 3.3 ng/mg((creatinine)) and 15.3 ng/mg((creatinine)), respectively. The exposure to ETS of restaurant workers in dining restaurants was clearly lower than that of workers in pubs and nightclubs as indicated by all ETS-markers used in the present study. During the work week, the cotinine and 3'-hydroxycotinine levels in urine of the study subjects increased. The correlation between breathing zone nicotine and urine cotinine and hydroxycotinine was 0.66 for both compounds. Post-shift cotinine and hydroxycotinine levels were not significantly higher than the pre-shift levels. CONCLUSIONS: If 9 ng cotinine/mg((creatinine)) is considered as the level above which heavy exposure has occurred, then this level was exceeded by 14 (approximately 60%) subjects at least once during the work week. Nicotine metabolite concentrations in the urine increased during the work week in 80% of the subjects, and the increase was especially noticeable for subjects working in both pubs and nightclubs. The study indicates that measures to restrict ETS exposure in restaurants are needed.     

Insulin and glucagon secretion in patients with slowly progressing autoimmune diabetes (LADA)

To metabolically characterize patients with slowly progressing autoimmune diabetes (LADA) of short duration we measured insulin, C peptide, and glucagon responses to glucose and arginine at three blood glucose levels (fasting and 14 and 28 mmol/L) in 11 patients with LADA, 11 patients with type 2 diabetes, and 14 healthy control subjects matched for age and body mass index. The acute insulin response to arginine was impaired in LADA vs. type 2 diabetes at all glucose levels, with the greatest impairment in the maximally stimulated insulin concentrations (P<0.04). In contrast, beta-cell sensitivity to glucose was unaltered in LADA and type 2 diabetes. The glucagon concentrations were elevated in both LADA and type 2 diabetic patients compared with healthy control subjects (P<0.02), but did not differ between the diabetic groups. In conclusion, patients with LADA share insulin resistance with type 2 diabetic patients, but display a more severe defect in maximally stimulated beta-cell capacity than patients with type 2 diabetes.     

Accuracy of medical models made by additive manufacturing (rapid manufacturing)

BackgroundAdditive manufacturing (AM) is being increasingly used for producing medical models. The accuracy of these models varies between different materials, AM technologies and machine runs.PurposeTo determine the accuracy of selective laser sintering (SLS), three-dimensional printing (3DP) and PolyJet technologies in the production of medical models.Material3D skull models: “original”, “moderate” and “worse”. SLS, 3DP and PolyJet models, and a coordinate measuring machine (CMM).MethodsMeasuring balls designed for measurements were attached to each 3D model. Skull models were manufactured using SLS, 3DP and PolyJet. The midpoints of the balls were determined using CMM. The distances between these points were calculated and compared with the 3D model.ResultsThe dimensional error for the PolyJet was 0.18 ± 0.12% (first measurement) and 0.18 ± 0.13% (second measurement), for SLS 0.79 ± 0.26% (first model) and 0.80 ± 0.32% (second model), and for 3DP 0.67 ± 0.43% (original model, first measurement) and 0.69 ± 0.44% (original model, second measurement), 0.38 ± 0.22% (moderate model) and 0.55 ± 0.37% (worse model). Repeatability of the measurement method was 0.12% for the PolyJet and 0.08% for the 3DP.ConclusionA novel measuring technique was developed and its repeatability was found to be good. The accuracy of the PolyJet was higher when compared with SLS or 3DP.     

Fatty fish consumption and risk of latent autoimmune diabetes in adults

Objective:

It has been suggested that intake of fatty fish may protect against both type 1 and type 2 diabetes. Hypotheses rest on the high marine omega-3 fatty acid eicosapentaenoic acid+docosahexaenoic acid (EPA+DHA) and vitamin D contents, with possible beneficial effects on immune function and glucose metabolism. Our aim was to investigate, for the first time, fatty fish consumption in relation to the risk of latent autoimmune diabetes in adults (LADA).

Methods:

Analyses were based on data from a Swedish case–control study with incident cases of LADA (n=89) and type 2 diabetes (n=462) and randomly selected diabetes-free controls (n=1007). Diabetes classification was based on the onset of age (⩾35), glutamic acid decarboxylase autoantibodies, and C-peptide. A validated food frequency questionnaire was used to derive information on previous intake of fish, polyunsaturated long-chain omega-3 fatty acids (n-3 PUFA) and supplementation of fish oil and vitamin D. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression, adjusted for age, gender, body mass index (BMI), family history of diabetes, physical activity, smoking, education, and consumption of alcohol, fruit, vegetables and red meat.

Results:

Weekly fatty fish consumption (⩾1 vs <1 serving per week), was associated with a reduced risk of LADA but not type 2 diabetes (OR 0.51, 95% CI 0.30–0.87, and 1.01, 95% CI 0.74–1.39, respectively). Similar associations were seen for estimated intake of n-3 PUFA (⩾0.3 g per day; LADA: OR 0.60, 95% CI 0.35–1.03, type 2 diabetes: OR 1.14, 95% CI 0.79–1.58) and fish oil supplementation (LADA: OR 0.47, 95% CI 0.19–1.12, type 2 diabetes: OR 1.58, 95% CI 1.08–2.31).

Conclusions:

Our findings suggest that fatty fish consumption may reduce the risk of LADA, possibly through effects of marine-originated omega-3 fatty acids.