ABSTRACT
BACKGROUND: Many patients with psoriasis have undiagnosed psoriatic arthritis. Low specificity is found with many PsA screening tools. A new instrument, the CONTEST questionnaire, was developed utilizing the most discriminative items from existing instruments. OBJECTIVE: The aim of this study was to compare the CONTEST and PEST screening tools. METHODS: People attending secondary care clinics with psoriasis, but not PsA, completed the questionnaires, were assessed for function and quality of life, and had a physical examination. Patients thought to have PsA were compared to those without. The performance of CONTEST and PEST was compared using area under the receiver operating curve (AUC), and sensitivity and specificity at the previously published cut-offs. RESULTS: A total of 451 dermatology patients were approached, 35% were reviewed and 27 (17%, 95% CI 12.3-21.7) had unidentified psoriatic arthritis. The sensitivity and specificity (95% CI) of PEST were 0.60 (0.42-0.78)/0.76 (0.69-0.83) and for CONTEST 0.53 (0.34-0.72)/0.71 (0.63-0.79). The confidence limits for the AUC overlapped (AUC for PEST 0.72 (0.61-0.84), for CONTEST 0.66 (0.54-0.77). CONCLUSIONS: PEST and CONTEST questionnaires performed equally well, with no superiority of the new CONTEST tool.
Subject(s)
Arthritis, Psoriatic/diagnosis , Mass Screening/methods , Surveys and Questionnaires , Adult , Area Under Curve , Arthritis, Psoriatic/complications , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Physical Examination , Psoriasis/complications , Quality of Life , ROC CurveABSTRACT
GABAergic interneurones, including those within spinal dorsal horn, contain one of the two isoforms of the synthesizing enzyme glutamate decarboxylase (GAD), either GAD65 or GAD67. The physiological significance of these two GABAergic phenotypes is unknown but a more detailed anatomical and functional characterization may help resolve this issue. In this study, two transgenic Green Fluorescent Protein (GFP) knock-in murine lines, namely GAD65-GFP and GAD67-GFP (Δneo) mice, were used to profile expression of Shaw-related Kv3.1b and Kv3.3 K(+)-channel subunits in dorsal horn interneurones. Neuronal expression of these subunits confers specific biophysical characteristic referred to as 'fast-spiking'. Immuno-labelling for Kv3.1b or Kv3.3 revealed the presence of both of these subunits across the dorsal horn, most abundantly in laminae I-III. Co-localization studies in transgenic mice indicated that Kv3.1b but not Kv3.3 was associated with GAD65-GFP and GAD67-GFP immunopositive neurones. For comparison the distributions of Kv4.2 and Kv4.3 K(+)-channel subunits which are linked to an excitatory neuronal phenotype were characterized. No co-localization was found between GAD-GFP +ve neurones and Kv4.2 or Kv4.3. In functional studies to evaluate whether either GABAergic population is activated by noxious stimulation, hindpaw intradermal injection of capsaicin followed by c-fos quantification in dorsal horn revealed co-expression c-fos and GAD65-GFP (quantified as 20-30% of GFP +ve population). Co-expression was also detected for GAD67-GFP +ve neurones and capsaicin-induced c-fos but at a much reduced level of 4-5%. These data suggest that whilst both GAD65-GFP and GAD67-GFP +ve neurones express Kv3.1b and therefore may share certain biophysical traits, their responses to peripheral noxious stimulation are distinct.
