Metformin ameliorates valve interstitial cell calcification by promoting autophagic flux.

Calcific aortic valve disease (CAVD) is the most common heart disease of the developed world. It has previously been established that metformin administration reduces arterial calcification via autophagy; however, whether metformin directly regulates CAVD has yet to be elucidated. In the present study we investigated whether metformin alleviates valvular calcification through the autophagy-mediated recycling of Runx2. Calcification was reduced in rat valve interstitial cells (RVICs) by metformin treatment (0.5-1.5 mM) (P < 0.01), with a marked decrease in Runx2 protein expression compared to control cells (P < 0.05). Additionally, upregulated expression of Atg3 and Atg7 (key proteins required for autophagosome formation), was observed following metformin treatment (1 mM). Blocking autophagic flux using Bafilomycin-A1 revealed colocalisation of Runx2 with LC3 puncta in metformin treated RVICs (P < 0.001). Comparable Runx2 accumulation was seen in LC3 positive autolysosomes present within cells that had been treated with both metformin and hydroxychloroquine in combination (P < 0.001). Mechanistic studies employing three-way co-immunoprecipitation with Runx2, p62 and LC3 suggested that Runx2 binds to LC3-II upon metformin treatment in VICs. Together these studies suggest that the utilisation of metformin may represent a novel strategy for the treatment of CAVD.

Survey on common reference intervals for general chemistry analytes in Hong Kong.

INTRODUCTION: Reference intervals (RIs) are essential tool for proper interpretation of results. There is a global trend towards implementing common RIs to avoid confusion and enhance patient management across different laboratories. However, local practices with respect to RIs lack harmonisation. METHODS: We have conducted the first local survey regarding RIs for 14 general chemistry analytes in 10 chemical pathology laboratories that employ four different analytical platforms (Abbott Architect, Beckman Coulter AU, Roche Cobas, and Siemens Dimension EXL). Analytical bias was assessed by an inter-laboratory results comparison of external quality assurance programmes. RESULTS: Sufficient inter-laboratory and inter-platform agreement regarding the 10 analytes (albumin, alanine aminotransferase, aspartate aminotransferase, chloride, gamma-glutamyl transferase, phosphate, potassium, sodium, total protein, and urea) were demonstrated. However, the RIs were heterogeneous across all laboratories, with percentage differences of the upper RI value of up to 47% for aspartate aminotransferase (absolute difference of 16 U/L), 29% for urea (1.8 mmol/L), and 18% for potassium (0.8 mmol/L). The percentage difference between lower RI values was up to 24% for urea (0.6 mmol/L), 22% for phosphate (0.16 mmol/L), and 8% for total protein (5 g/L). The coefficients of variation of the upper RI values of potassium and sodium were 1.2 times and 1.0 times of their corresponding between-subject biological variation, respectively, representing unnecessary variations that are overlooked and unchecked in current practice. CONCLUSIONS: We recommend the use of common RIs for general chemistry analytes in Hong Kong to prevent interpreter confusion, improve electronic data transfer, and unite laboratory practice. This is the first local study on this topic, and our data can lay the groundwork for increasing harmonisation of RIs across more laboratory tests.

A study of contralateral persistent processus vaginalis in laparoscopic hernia repair in children.

PURPOSE: The introduction of laparoscopy for hernia repair permits intra-abdominal observation of a hernia and contralateral persistent processus vaginalis (CPPV). The current study's aim was to investigate the diameter of opening of an inguinal hernia and CPPV in patients with unilateral inguinal hernia, and to evaluate their correlation with age. METHODS: From September 2012 to August 2017, 569 pediatric patients underwent laparoscopic repair of unilateral inguinal hernia. We retrospectively evaluated the size of the hernia and CPPV by measuring the diameter of opening. Pearson correlation analysis and linear-by-linear association were used in the statistical analysis. RESULTS: The median age at operation was 32.4 months (range 0.2-219 months). CPPV was observed in 330 patients (58.0%), and its incidence was significantly higher in patients with left inguinal hernias than in those with right inguinal hernias (62.8 versus 54.0%, p < 0.001). The mean diameter of opening for the hernias was significantly larger than that for CPPV (11.2 ± 3.1 vs. 6.1 ± 2.5 mm, p < 0.001). The incidence of CPPV gradually decreased from 77.2% in infants to 46.6% in the oldest age group (≥ 6 years) (p trend < 0.001). The diameter of the opening of a hernia was not correlated with increasing age, and the diameter of the opening of a CPPV was not correlated with increasing age, as well. CONCLUSION: The diameters of a hernia and CPPV were identified in the current study, and the diameter was not correlated with increasing age. The incidence of CPPV was more common in patients with left inguinal hernias than in those with right inguinal hernias, and it gradually decreased with increasing age.

L-Arginine supplementation enhances growth performance, lean muscle, and bone density but not fat in broiler chickens.

This study evaluated the effects of crystalline arginine (Arg) on performance and body composition in male broilers. A total of 600 1-day-old Ross 308 broilers were distributed in a completely randomized design, with 5 treatments and 6 replicates of 20 birds. The treatments were given as a percentage of the Ross 308 requirement, and defined as 70, 80, 90, 100 (Ross 308 requirement), and 110% of Arg. Body weight gain (BWG), feed intake (FI), and feed conversion ratio (FCR) were evaluated at 10, 24, and 42 d. Bone growth was measured from 7 to 11 d using mineral apposition rate (MAR) technique. At 42 d, 2 birds per pen were euthanized for bone mineral density (BMD) and body composition measurement using dual-energy X-ray absorptiometry, and liver gene expression and muscle diameter size analysis. The means were subjected to ANOVA and, when significant (P ≤ 0.05), were compared by Dunnett's test. Regression analyses were performed to evaluate trends of Arg dose response. Birds fed 70 and 80% of Arg had lower BWG than the ones fed 100% of Arg (P < 0.001), with quadratic effects for all phases (P < 0.001, R2 = 0.94). The 70% of Arg group showed lower FI compared to 100% from 11 to 24 d and 1 to 42 d (P < 0.009), with quadratic and linear effects (P < 0.049, R2 > 0.72), respectively. The 70% of Arg group showed higher FCR compared to 100% (P < 0.0001) with quadratic effects (P < 0.002, R2 > 0.94) for all periods. At 42 d, the 70% of Arg group showed lower BMD, tissue, and lean muscle percentage than 100% of Arg. There was a quadratic effect of Arg levels on lean muscle (P = 0.046, R2 = 0.89). Therefore, the dietary supplementation with Arg is necessary as it leads to an overall body growth with increased lean deposition and BMD, without increasing fat accretion in Ross 308 broiler chickens.

Implication of Major Adverse Postoperative Events and Myocardial Injury on Disability and Survival: A Planned Subanalysis of the ENIGMA-II Trial.

BACKGROUND: Globally, >300 million patients have surgery annually, and ≤20% experience adverse postoperative events. We studied the impact of both cardiac and noncardiac adverse events on 1-year disability-free survival after noncardiac surgery. METHODS: We used the study cohort from the Evaluation of Nitrous oxide in Gas Mixture of Anesthesia (ENIGMA-II) trial, an international randomized trial of 6992 noncardiac surgical patients. All were ≥45 years of age and had moderate to high cardiac risk. The primary outcome was mortality within 1 postoperative year. We defined 4 separate types of postoperative adverse events. Major adverse cardiac events (MACEs) included myocardial infarction (MI), cardiac arrest, and myocardial revascularization with or without troponin elevation. MI was defined using the third Universal Definition and was blindly adjudicated. A second cohort consisted of patients with isolated troponin increases who did not meet the definition for MI. We also considered a cohort of patients who experienced major adverse postoperative events (MAPEs), including unplanned admission to intensive care, prolonged mechanical ventilation, wound infection, pulmonary embolism, and stroke. From this cohort, we identified a group without troponin elevation and another with troponin elevation that was not judged to be an MI. Multivariable Cox proportional hazard models for death at 1 year and assessments of proportionality of hazard functions were performed and expressed as an adjusted hazard ratio (aHR) and 95% confidence intervals (CIs). RESULTS: MACEs were observed in 469 patients, and another 754 patients had isolated troponin increases. MAPEs were observed in 631 patients. Compared with control patients, patients with a MACE were at increased risk of mortality (aHR, 3.36 [95% CI, 2.55-4.46]), similar to patients who suffered a MAPE without troponin elevation (n = 501) (aHR, 2.98 [95% CI, 2.26-3.92]). Patients who suffered a MAPE with troponin elevation but without MI had the highest risk of death (n = 116) (aHR, 4.29 [95% CI, 2.89-6.36]). These 4 types of adverse events similarly affected 1-year disability-free survival. CONCLUSIONS: MACEs and MAPEs occur at similar frequencies and affect survival to a similar degree. All 3 types of postoperative troponin elevation in this analysis were associated, to varying degrees, with increased risk of death and disability.

Dimerization leads to changes in APP (amyloid precursor protein) trafficking mediated by LRP1 and SorLA.

Proteolytic cleavage of the amyloid precursor protein (APP) by α-, ß- and γ-secretases is a determining factor in Alzheimer's disease (AD). Imbalances in the activity of all three enzymes can result in alterations towards pathogenic Aß production. Proteolysis of APP is strongly linked to its subcellular localization as the secretases involved are distributed in different cellular compartments. APP has been shown to dimerize in cis-orientation, affecting Aß production. This might be explained by different substrate properties defined by the APP oligomerization state or alternatively by altered APP monomer/dimer localization. We investigated the latter hypothesis using two different APP dimerization systems in HeLa cells. Dimerization caused a decreased localization of APP to the Golgi and at the plasma membrane, whereas the levels in the ER and in endosomes were increased. Furthermore, we observed via live cell imaging and biochemical analyses that APP dimerization affects its interaction with LRP1 and SorLA, suggesting that APP dimerization modulates its interplay with sorting molecules and in turn its localization and processing. Thus, pharmacological approaches targeting APP oligomerization properties might open novel strategies for treatment of AD.

Temperature-dependent impact of thermal aminolaevulinic acid photodynamic therapy on apoptosis and reactive oxygen species generation in human dermal fibroblasts.

BACKGROUND: Actinic keratoses (AKs) are generally accepted as common precursor lesions to invasive squamous cell carcinoma. Photodynamic therapy (PDT) is a common, in-office, field therapy modality used in the treatment of AKs. Clinical and laboratory observations have demonstrated that temperature modulation can affect PDT efficacy. OBJECTIVES: To demonstrate thermal PDT increases apoptotic cell death, and to investigate the mechanistic role of reactive oxygen species (ROS) free radicals in an in vitro human skin fibroblast model. METHODS: This study was completed using commercially available primary human skin fibroblasts treated with aminolaevulinic acid (ALA) at specific concentrations and controlled temperatures. Cell death, apoptosis and superoxide ROS levels were quantified. RESULTS: We found that thermal PDT with 0·5 mmol L(-1) ALA resulted in significant temperature-dependent increases in total apoptosis and superoxide ROS generation between 33 °C and 42 °C. CONCLUSIONS: Our results indicate that thermal PDT significantly increases apoptotic cell death through increased generation of superoxide ROS in a temperature-dependent manner.

Automated preoperative assessment of endothelial dysfunction and risk stratification for perioperative myocardial injury in patients undergoing non-cardiac surgery.

BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) is a common complication with associated serious morbidity and mortality. Endothelial dysfunction might play an important role in MINS, and its rapid assessment could provide a novel method of risk stratification before surgery. METHODS: We studied 238 subjects scheduled to undergo intermediate or high-risk surgery in a two-centre prospective study to determine whether preoperative endothelial dysfunction identified by a reactive hyperaemia-peripheral arterial tonometry (RH-PAT) index could provide effective risk stratification for MINS, defined as serum troponin ≥0.04 µg litre(-1), within 3 postoperative days. RESULTS: The primary outcome occurred in 35 subjects (14.7%). Endothelial dysfunction was defined as an RH-PAT index of ≤1.22. Adjusted for age, Lee index and a composite measure of the extent of surgery, endothelial dysfunction was associated with MINS [odds ratio 10.1, 95% confidence interval (CI) 3.3-30.9, P=0.001] and increased time to discharge from hospital after surgery (hazard ratio 0.39, 95% CI 0.23-0.65, P=0.001). Endothelial dysfunction identified MINS with a sensitivity of 31%, a specificity of 96%, and a positive diagnostic likelihood ratio of 8.0. Risk classification for MINS was improved by the addition of RH-PAT-defined endothelial dysfunction to the Lee index (c-statistic increased from 0.69 to 0.77; integrated discrimination improvement 0.11, P=0.003). However, prognostic utility varied widely between sites. CONCLUSIONS: For patients undergoing non-cardiac surgery, non-invasive assessment of endothelial function might enhance preoperative risk stratification for perioperative myocardial injury. However, unexplained large inter-site variation in prognostic utility could limit widespread application and needs to be further understood.

Syntaxin-3 regulates newcomer insulin granule exocytosis and compound fusion in pancreatic beta cells.

AIMS/HYPOTHESIS: The molecular basis of the exocytosis of secretory insulin-containing granules (SGs) during biphasic glucose-stimulated insulin secretion (GSIS) from pancreatic beta cells remains unclear. Syntaxin (SYN)-1A and SYN-4 have been shown to mediate insulin exocytosis. The insulin-secretory function of SYN-3, which is particularly abundant in SGs, is unclear. METHODS: Mouse pancreatic islets and INS-1 cells were treated with adenovirus carrying Syn-3 (also known as Stx3) or small interfering RNA targeting Syn-3 in order to examine insulin secretion by radioimmunoassay. The localisation and distribution of insulin granules were examined by confocal and electron microscopy. Dynamic single-granule fusion events were assessed using total internal reflection fluorescence microscopy (TIRFM). RESULTS: Depletion of endogenous SYN-3 inhibited insulin release. TIRFM showed no change in the number or fusion competence of previously docked SGs but, instead, a marked reduction in the recruitment of newcomer SGs and their subsequent exocytotic fusion during biphasic GSIS. Conversely, overexpression of Syn-3 enhanced both phases of GSIS, owing to the increase in newcomer SGs and, remarkably, to increased SG-SG fusion, which was confirmed by electron microscopy. CONCLUSIONS/INTERPRETATION: In insulin secretion, SYN-3 plays a role in the mediation of newcomer SG exocytosis and SG-SG fusion that contributes to biphasic GSIS.

Pivotal role of the RanBP9-cofilin pathway in Aß-induced apoptosis and neurodegeneration.

Neurodegeneration associated with amyloid ß (Aß) peptide accumulation, synaptic loss, neuroinflammation, tauopathy, and memory impairments encompass the pathophysiological features of Alzheimer's disease (AD). We previously reported that the scaffolding protein RanBP9, which is overall increased in brains of AD patients, simultaneously promotes Aß generation and focal adhesion disruption by accelerating the endocytosis of amyloid precursor protein (APP) and ß1-integrin, respectively. Here, we show that RanBP9 protein levels are increased by fourfold in FAD mutant APP transgenic mice. Accordingly, RanBP9 transgenic mice demonstrate significantly increased synapse loss, neurodegeneration, gliosis, and spatial memory deficits. RanBP9 overexpression promotes apoptosis and potentiates Aß-induced neurotoxicity independent of its capacity to promote Aß generation. Conversely, RanBP9 reduction by siRNA or gene dosage mitigates Aß-induced neurotoxicity. Importantly, RanBP9 activates/dephosphorylates cofilin, a key regulator of actin dynamics and mitochondria-mediated apoptosis, and siRNA knockdown of cofilin abolishes both Aß and RanBP9-induced apoptosis. These findings implicate the RanBP9-cofilin pathway as critical therapeutic targets not only for stemming Aß generation but also antagonizing Aß-induced neurotoxicity.

Red flags and alarm bells: an atypical lesion masquerading as a diabetic foot ulcer.

An 88-year-old male presented at a high-risk foot service with a non-healing, plantar wound on his right foot, which had the appearance of a neuropathic ulcer. On further examination, the lesion was confirmed asymmetrical in shape and atypical in appearance. It also presented with surrounding violaceous, pigmented nodules in the arch of the foot, and several small, similar nodules on the plantar surface of the contralateral foot, giving the appearance of an exophytic lesion and suggesting melanoma. Following biopsy, it was diagnosed as classic Kaposi sarcoma.

Comparison of the Psoriatic Arthritis Quality of Life (PsAQoL) questionnaire, the functional status (HAQ) and utility (EQ-5D) measures in psoriatic arthritis: results from a cross-sectional survey.

OBJECTIVES: To compare the Psoriatic Arthritis Quality of Life (PsAQoL) instrument, the Health Assessment Questionnaire (HAQ) as a measure of functional status, and the generic health status (utility) measure the EuroQoL (EQ-5D) in terms of ability to assess disease severity in psoriatic arthritis (PsA). METHODS: The differences between known groups and correlations of the PsAQoL, the HAQ and the EQ-5D with clinical measures were analysed in a sample of 183 PsA patients. RESULTS: Different severities of PsA determined by known groups were distinguished well by all three questionnaires; more severe disease was associated with significantly worse values of the instruments. The correlations revealed a strong relationship between each of the measures, and with the patients' pain on the visual analogue scale (VAS), the patient global VAS, and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and a weak relationship with the disease duration and the Psoriasis Area Severity Index (PASI). The PsAQoL also correlated strongly with the 28-joint Disease Activity Score (DAS28). CONCLUSIONS: The PsAQoL, the HAQ, and the EQ-5D are able to distinguish well across levels of PsA severity.

Amiodarone offsets the cardioprotective effects of ischaemic preconditioning against ischaemia/reperfusion injury.

Both ischaemic preconditioning (IPC) and amiodarone protect against myocardial ischaemia. We examined whether a combination of IPC and amiodarone demonstrated an additive protective effect in isolated rat hearts (n = 40). The controls (group I) were subjected to ischaemia/ reperfusion injury; group II was subjected to cycles of IPC prior to ischaemia/ reperfusion injury; group III was subjected to ischaemia in the presence of amiodarone (10(-10) mol/1); and group IV was subjected to IPC followed by ischaemia in the presence of amiodarone (10(-10) mol/l). Amiodarone produced the best preserved left ventricular end-systolic pressure and dP/dtmax, less developed ventricular stiffness, the shortest arrhythmia duration, and the smallest infarct size among the groups. All of the myocardial protective effects against ischaemia/reperfusion injury were diminished or abolished when IPC and amiodarone were applied sequentially.

Abeta induces cell death by direct interaction with its cognate extracellular domain on APP (APP 597-624).

Amyloid beta-peptide (Abeta) is postulated to play a central role in the pathogenesis of Alzheimer's disease. We recently proposed a pathway of Abeta-induced toxicity that is APP dependent and involves the facilitation of APP complex formation by Abeta. The APP-dependent component requires cleavage of APP at position 664 in the cytoplasmic domain, presumably by caspases or caspase-like proteases, with release of a potentially cytotoxic C31 peptide. In this study we show that Abeta interacted directly and specifically with membrane-bound APP to facilitate APP homo-oligomerization. Using chimeric APP molecules, this interaction was shown to take place between Abeta and its homologous sequence on APP. Consistent with this finding, we demonstrated that Abeta also facilitated the oligomerization of beta-secretase cleaved APP C-terminal fragment (C99). We found that the YENPTY domain in the APP cytoplasmic tail and contained within C31 is critical for this cell death pathway. Deletion or alanine- scanning mutagenesis through this domain significantly attenuated cell death apparently without affecting either APP dimerization or cleavage at position 664. This indicated that sequences within C31 are required after its release from APP. As the YENPTY domain has been shown to interact with a number of cytosolic adaptor molecules, it is possible that the interaction of APP, especially dimeric forms of APP, with these molecules contribute to cell death.

Gastrointestinal safety of amtolmetin guacyl in comparison with celecoxib in patients with rheumatoid arthritis.

OBJECTIVE: Selective inhibitors of cyclo-oxygenase-2 (COX-2) appear to be safer than conventional NSAIDs on the gastrointestinal (GI) tract. Amtolmetin guacyl (AMG), a NSAID that inhibits both COX-1 and COX-2, has an anti-inflammatory effect comparable to that of traditional NSAIDs, with a better GI safety profile. The primary end-point of this study was to evaluate the gastrointestinal safety of amtolmetin guacyl in comparison with celecoxib in patients affected with rheumatoid arthritis. The assessment of efficacy was the secondary end-point. METHODS: This study was a 24-week, randomized, parallel group, double-blind, double dummy, multicentre trial; 235 patients were enrolled and 180 patients (85 in the AMG group and 95 in the celecoxib group) completed the study. Each patient received twice daily amtolmetin guacyl 600 mg or celecoxib 200 mg. Assessment of safety was performed by upper GI endoscopy, gastrointestinal symptoms evaluation, electrocardiography, blood and urine laboratory tests, adverse events recording. Assessment of efficacy was performed by using the American College of Rheumatology (ACR-20) responder index. RESULTS: Neither amtolmetin guacyl nor celecoxib determined a worsening of baseline gastro-duodenal endoscopy findings. The percentage of patients with normal findings did not significantly change after treatment with both drugs, being virtually identical with AMG (i.e. 75.29%) and increasing from 75.79% to 77.66% with celecoxib. Moreover an evaluation of the other safety parameters did not reveal any difference between the two treatment groups. Therapeutic efficacy was equivalent in both groups, with no statistical difference between the two drugs at all time intervals. CONCLUSIONS: In patients affected with rheumatoid arthritis, AMG and celecoxib proved to be equivalent, showing comparable gastrointestinal safety and therapeutic efficacy of treatment.

[Immunohistochemical analysis of the expression of main adhesion molecules and tumor necrosis factors in the synovial membrane of psoriatic arthritis]. / Analisi immunoistochimica dell'espressione delle principali molecole di adesione e dei fattori di necrosi tumorale a livello della membrana sinoviale nell'artrite psoriasica.

OBJECTIVE: To define the expression and pattern of the synovial distribution of adhesion molecules such as E-selectin, ICAM-1 and VCAM-1 and of TNFalpha and TNFbeta cytokines in psoriatic arthritis (PsA), according to the synovitis duration. METHODS: Cryostatic sections of the synovial membrane tissue samples were stained for the different antibodies using a standard three-stage-immunoperoxidase-labeling technique. RESULTS: E-selectin grade of staining was higher in those patients with a shorter disease duration compared to longstanding synovitic specimens, as well as ICAM-1 expression. On the contrary a higher VCAM-1 positivity was mainly found in longstanding PsA patients. Anti-TNFalpha positivity was found almost in all the specimens with no difference among the two groups, while the intensity of anti-TNFbeta positivity was globally higher in longstanding cases. CONCLUSIONS: Different adhesion molecules may separately participate to the synovitic process in the different phases of PsA, leading to the hypothesis of their different involvement during the disease evolution. Moreover the upregulation of TNFalpha and TNFbeta gives evidence to their local proinflammatory effect within the synovium and to their role in perpetuating the PsA synovitis.

Termination of disease-modifying antirheumatic drugs in rheumatoid arthritis and in psoriatic arthritis. A comparative study of 270 cases.

102 rheumatoid arthritis (RA) and 104 psoriatic arthritis (PsA) patients' records were analysed according to a standardised protocol. Using Cox regression, life-table analysis and log rank test, the effectiveness and toxicity of, and duration of disease modifying antirheumatic drug (DMARD) treatment were compared in RA and PsA. RA patients were treated with gold sodium thiomalate (GST), methotrexate (MTX) and sulphasalazine (SSZ) for a median duration of 35, 72 and 12 months respectively, whereas PsA patients were treated for 12, 12 and 17 months. The differences for GST and MTX were statistically significant (p=0.0043 and 0.0447). Drug toxicity was more frequently seen among patients with PsA (p=0.0023). No difference in efficacy could be proved. Results suggest that there is a significant difference between RA and PsA patients in terms of toxicity of these agents. Therefore, separate treatment strategies are needed, and earlier results with RA may not be directly applicable to PsA.

Elevated levels of synovial fluid antibodies reactive with the small proteoglycans biglycan and decorin in patients with rheumatoid arthritis or other joint diseases.

OBJECTIVES: To determine whether patients with rheumatoid arthritis (RA) express humoral immunity to the small proteoglycans biglycan and decorin and to compare the response to that of patients suffering from other joint diseases. METHODS: Serum and synovial fluid IgG and IgM antibody levels were determined by enzyme-linked immunosorbent assay. Antibodies to biglycan and decorin as well as to other known and extensively investigated cartilage matrix components such as type II collagen, aggrecan and fibronectin were investigated. Patients suffering from RA, osteoarthritis (OA), psoriatic arthritis and other seronegative spondylarthropathies were included in the study. Correlation between antibody levels and clinical/laboratory parameters was determined. RESULTS: Patients with RA expressed an increased humoral immunity to biglycan, while patients with seronegative spondylarthropathies displayed elevated decorin-specific synovial antibody levels compared with OA patients. CONCLUSION: These results indicate a significantly higher immunity to small proteoglycans in RA and seronegative spondylarthropathies than in OA suggesting a possible involvement in the pathogenesis of inflammatory rheumatic diseases.

Measurement of disease activity in psoriatic arthritis. Extended report.

OBJECTIVE: To determine whether activity indices, generally accepted in rheumatoid arthritis (RA) are useful and valid to measure disease activity in psoriatic arthritis (PsA) patients with peripheral arthritis. METHODS: 38 PsA patients were studied before and after a one year DMARD treatment. Extended and reduced tender and swollen joint counts, Ritchie articular index, Health Assessment Questionnaire HAQ) score, erythrocyte sedimentation rate (ESR) morning stiffness, the patient's and the assessor's global assessment (PGA and AGA) were recorded. Disease activity scores, EULAR, ACR and Clegg improvement criteria were calculated. RESULTS: All indices correlated well before and after treatment with AGA (r > 0.337, p < 0.042), except morning stiffness and tender joint counts. After treatment, PGA correlated well only with the 68 and 28 tender joint counts, ESR and HAQ (r > 0.340, p < 0.05). The response to DMARD treatment was well characterized with the changes in the number of tender and swollen joint counts, and DAS4, DAS3, DAS28. The changes correlated with the PGA and AGA. The level of agreement between Clegg and the EULAR improvement criteria with both extended and reduced joint count was comparable (p < 0.01). CONCLUSION: The well-known activity indices generally accepted in RA, as tender and swollen joint count, DAS3, DAS4, DAS28, are useful and valid indices measuring arthritis activity in PsA with peripheral arthritis. The correlation between Clegg and EULAR improvement classification indices were similar. Both seemed to characterize changes authenticated during DMARD treatment.