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Objectives: The existing set of outcomes for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) needs to incorporate views of outcome measure stakeholders to meet the current standards of outcome measurement proposed by the Outcome Measures in Rheumatology (OMERACT) initiative. This study identifies domains that clinical experts (one group of stakeholders) consider to be important to determining the impact of AAV using the International Classification of Functioning, Disability and Health (ICF), a framework that describes health along four components: body functions, body structures, activities and participation, and contextual factors.Method: An international group of clinicians with expertise in the clinical care of patients with vasculitis were identified through consultation with three major vasculitis societies. The relevant domains were determined using a three-round e-mail-based Delphi questionnaire.Results: Eighty-two clinicians were invited to participate in this study and 41 responded. Nineteen domains were identified as important by > 80% of participants: six body functions (energy, seeing, hearing, pain, respiratory, and renal function), seven body structures (peripheral nerves, eye, ear, nose, sinuses, lungs (and airways), and kidneys), three activities and participation (carrying out daily routine, remunerative employment, and recreation and leisure), and three environmental factors (medications, support and relationships, and health services, systems, and policies).Conclusions: Clinical experts focus on the physiological effects of AAV with less importance given to the effect of AAV on patients' activities and participation in life situations and the role of contextual factors. This study represents a step towards incorporating views of a range of stakeholders into disease assessment in AAV. [ABSTRACT FROM AUTHOR]

Background: Blau syndrome is a chronic granulomatous disease with an autosomal dominant trait characterized by the triad granulomatous dermatitis, arthritis, and uveitis. It is caused by mutations in the NOD2 gene, also termed the CARD15 gene. Objective: To report a novel mutation in the NOD2 gene associated with Blau syndrome. Methods and results: The proband was a 68-year-old ethnic Norwegian male who had uveitis and arthritis since 10 years of age followed by lifelong recurrent arthritis and chronic eye involvement. Genetic analysis showed a heterozygous c.1814 C>A, T605N mutation in NOD2 that has not previously been described. All of his three children had Blau syndrome and had inherited the NOD2 mutation. The proband's first son had exanthema, arthritis, and uveitis from 10 years of age and later presented with granulomatous lymphadenopathy, granulomatous parotitis, and granulomatous intestinal inflammation. The proband's daughter had arthritis, uveitis, and exanthema from 3 years of age. The proband's second son had uveitis, exanthema, and arthritis from 1.5 years of age. None of the cases had any involvement of the heart or lungs. Conclusion: We report a novel Blau syndrome-associated mutation with an autosomal dominant heritage. Most likely the mutation has arisen de novo in the proband. Genetic counselling and antenatal diagnostics should be available to the involved families. [ABSTRACT FROM AUTHOR]

Objective. Trefoil factors (TFF1-3) are 7-12 kDa peptides secreted by mucosal surfaces, with changing levels of expression reflected in serum concentrations. The genes for the peptides are located on chromosome 21, the chromosome duplicated in trisomy 21. We studied the levels of circulating TFFs in pregnant women carrying trisomy 21 foetuses and in women with normal pregnancies, throughout pregnancy and postpartum. Material and methods. Employing ELISA methods, serum collected at gestational weeks (GW) 18, 32, 39 and 8 weeks postpartum from women carrying normal foetuses (n = 141) was analysed for TFFs. In addition, serum collected at GW 6-14 (median = 10) from women carrying trisomy 21 foetuses (n = 48) or healthy foetuses (n = 46) was analysed. Results. Peaking at 39 GW, concentrations of TFF2 and TFF3 were 3.5 and 47 times higher, respectively, than postpartum. Postpartum levels were comparable to concentrations previously measured in non-pregnant women. TFF1 concentrations rose throughout pregnancy and postpartum, being 1.5 times higher postpartum compared to 18 GW. No differences in the levels of TFFs were observed between women carrying trisomy 21 and those with healthy foetuses. To our knowledge, circulating TFF3 has never been reported to reach the levels observed here. Also, the pattern of increase is unusual, as previous reports have shown parallel increases in TFF1 and TFF3 with no alterations in TFF2. Conclusions. Our results demonstrate that circulating TFFs are not candidate markers of trisomy 21 in first-trimester pregnancies, but raise intriguing questions concerning the origin of TFFs produced during pregnancy and their physiological function. [ABSTRACT FROM AUTHOR]

Analysis of the common C282Y and H63D mutations in the HFE gene is widely used to diagnose hereditary hemochromatosis (HH). The aim of this study was to evaluate the efficiency with which different hospitals and general practitioners select patients for HH genotype and to determine the distribution of HFE mutations in such patients. Nine hundred unrelated patients from Danish hospitals and general practitioners (group A) and 69 consecutive patients from a specialized liver unit (group B) were examined for HFE substitutions using multiplex real-time polymerase chain reaction. In group A we found 13.0% (0%) C282Y homozygotes, 5.8% (2.6%) H63D/C282Y compound heterozygotes and 1.9% (3.1%) S65C heterozygotes. The values for 420 Danish blood donors are shown in parentheses. The distribution of genotypes in group B was similar to that of the blood donors. Serum ferritin, transferrin iron saturation and pathological data were collected from 38 randomly selected C282Y homozygotes, 36 H63D/C282Y compound heterozygotes, 19 H63D heterozygotes, 17 S65C heterozygotes and 144 wild-types. All of the C282Y homozygotes and 28% of the compound heterozygotes were diagnosed as HH patients. There was no evidence of HH in the H63D homozygotes or S65C heterozygotes. Moreover, 7 wild-type patients, 2 C282Y heterozygote patients and one H63D heterozygote patient fulfilled the criteria for HH. The significant enrichment of HH among associated genotype samples submitted for HFE testing indicates that the clinical selection is generally adequate. However, the study showed substantial deviation in the selection efficiency among the various hospitals and general practitioners. [ABSTRACT FROM AUTHOR]