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Because there is the impression that psoriatic arthritis is a composite disorder with mild forms close to more severe and aggressive ones, we conducted a multicenter study with the aim of characterizing disease expression in a large cohort of Italian patients. One-thousand-three-hundred-six patients fulfilled inclusion criteria and were analyzed in this study. Psoriasis antedated the onset of arthritis in the majority of the cases (67.7%). More rare was inverse or simultaneous onset which occurred in 17.3% and 15.0% of the cases, respectively. Peripheral articular involvement (mono-oligo or polyarthritis) was recorded in 88.7% of the cases while spondylitis occurred in 11.3%. Peripheral enthesopathies were found in 28.1% of the cases with a marked occurrence in patients with axial involvement (64.5% vs 35.5% in oligo or polyarthritis). Abnormal levels of ESR and CRP respectively occurred in 52.2% and in 52.6% of the cases, while rheumatoid factor was detected in 5.0% of the cases. On the basis of distribution of joint involvement, symmetry and presence of peripheral enthesopathies we recognized three clusters of arthritis. Patients included in Cluster 1 and Cluster 2 showed a severe form of polyarthritis in most of the cases (82.9%), with increased serum levels of inflammatory indices in more than 85% of the cases. Almost all the hospitalized patients (97.1%) were included in this two clusters. They markedly assumed steroids and methotrexate or another DMARD. About half of the patients (51.1%) included in Cluster 3 showed mono-oligo articular involvement. Serum inflammatory indices were increased in 20.8% of the cases while hospitalization occurred only in 2.9% of the cases and NSAIDs were the treatment of choice. The evidence in our country of a large prevalence of severe forms of arthritis needing specific and aggressive approach outlines the requirement of an intense educational action aimed at increasing the awareness of this condition.

Objective: The aim of this study was to compare imaging findings obtained with different techniques in a patient with juvenile chronic arthritis. Methods: The patient was a 12 years-old child with a 7-months history of arthritis of the first metatarsophalangeal joint of the right foot. The involved area was explored with the following imaging techniques: X-ray, technetium bone scintigraphy, magnetic resonance, gray-scale and power-Doppler ultrasonography. Results: No abnormalities were detected with conventional X-ray. Scintigraphy showed an abnormal uptake of the radionuclide in the first metatarsophalangeal joint of the right foot. Magnetic resonance without contrast revealed clearly evident features of an active process of synovitis. Ultrasonography was able to detect the presence of joint effusion, synovial proliferation, bone erosion of the first metatarsal head. Power-Doppler examination revealed evident signs of soft tissue hyperemia. Conclusions: Comparative assessment of different imaging techniques in this patient with recent-onset juvenile chronic arthritis indicates that high resolution ultrasonography provides the most detailed evaluation of the joint involvement with respect to the other imaging techniques.

Cassava is the second most important staple food crop for Uganda and is prone to contamination with mycotoxins. This study aimed at understanding the current agricultural practices, their potential influence on mycotoxin occurrence, as well as assessing mycotoxin knowledge among key cassava value chain actors, including farmers, wholesalers, and processors. Data were collected through individual interviews (210), key informant interviews (34), and 4 focus group discussions. The findings revealed that 51% of farmers peeled cassava directly on bare ground, resulting in direct contact with soil that potentially harbors mycotoxin-producing fungi, such as Aspergillus section Flavi. During postharvest handling, 51.6% of farmers dried cassava chips directly on bare ground. Nearly, all (95.2%) of wholesalers packed cassava chips in local gunny bags and placed them on ground instead of pallets. In the processing of cassava chips into flour, only one of the 14 processing machines was certified by the Uganda National Bureau of Standards. Additionally, there was only one processing machine available for every 180 (1:180) consumers bringing their cassava for processing. 50.8% of cassava consumers interviewed admitted to consuming cassava flour regardless of quality, while 73% blended cassava flour with flour from mycotoxin-susceptible crops mainly maize, millet, and sorghum. Most (96.2%) of the people along the cassava value chain did not understand what the term mycotoxins meant. However, 56% of interviewed respondents were familiar with the term aflatoxins. Of the cassava value chain actors aware of mycotoxins, 82.9% knew of methods for reducing aflatoxin contamination, but only 40.9% were putting such methods into practice. More farmers (47.9%) managed aflatoxins compared to wholesalers (33.3%) and processors (21.4%). Knowledge on aflatoxins was significantly associated with value chain actor (P = 0.026), head of household (P = 0.004), region (P = 0.033), age (P = 0.001), and experience (P = 0.001). This study highlights the critical areas of mycotoxin contamination within the cassava value chain in Uganda and underscores the need to improve the knowledge among value chain actors especially farmers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

This study investigated the occurrence and distribution of multiple mycotoxins (aflatoxin B 1 , B 2 , G 1 , G 2 , fumonisins B 1 , B 2 , ochratoxin A (OTA), deoxynivalenol (DON), zearalenone (ZEN), and citrinin (CIT)) in cassava products and as assessed the potential risk of aflatoxin B1 (AFB 1 ) exposure among cassava consumers. A total of 192 samples of cassava products (96 flour and 96 chips, each with 48 samples from farmer and 48 from wholesaler) were analysed using LC/MS-MS. All positive samples irrespective of their origin (flour or chips) exhibited AFB 1 levels exceeding the EU regulatory threshold of 5 µg/kg. The sum of fumonisins (FB 1  + FB 2 ), ZEN, and DON were significantly (P < 0.05) higher in cassava flour (14.3 µg/kg; 3.71 µg/kg; 25.1 µg/kg) compared to chips (6.54 µg/kg; 1.25 µg/kg; 0.25 µg/kg), respectively. Aflatoxins G 2 was not detected in any of 192 samples. Cassava flour samples from farmers exhibited significantly (P < 0.05) higher mean concentrations of AFB 1 (27.1 µg/kg), total aflatoxins (78.2 µg/kg), and ochratoxin A (79.6 µg/kg) in contrast to wholesalers, whose mean levels were notably lower at 8.91, 5.79 µg/kg, and 2.44 µg/kg, respectively, pointing the likely critical source of mycotoxin contamination. Cassava consumers in Northern Uganda are at a higher risk, with an estimated 2.06 cancer cases per 100,000 individuals per year compared to those in Eastern Uganda at 0.25. This study underscores the urgent need for interventions to manage aflatoxins in cassava flour, particularly at farm level in Northern Uganda. It accentuates a shift market to household-level sampling and the need for analytical methods targeting multiple mycotoxins., (© 2024. Crown.)

Fusarium asiaticum is a predominant fungal pathogen causing Fusarium Head Blight (FHB) in wheat and barley in China and is associated with approximately £201 million in annual losses due to grains contaminated with mycotoxins. F. asiaticum produces deoxynivalenol and zearalenone whose maximum limits in cereals and cereals-derived products have been established in different countries including the EU. Few studies are available on the ecophysiological behaviour of this fungal pathogen, but nothing is known about the impact of projected climate change scenarios on its growth and mycotoxin production. Therefore, this study aimed to examine the interacting effect of i) current and increased temperature (25 vs 30 °C), ii) drought stress variation (0.98 vs 0.95 water activity; a w ) and iii) existing and predicted CO 2 concentrations (400 vs 1000 ppm) on fungal growth and mycotoxin production (type B trichothecenes and zearalenone) by three F. asiaticum strains (CH024b, 82, 0982) on a wheat-based matrix after 10 days of incubation. The results showed that, when exposed to increased CO 2 concentration (1000 ppm) there was a significant reduction of fungal growth compared to current concentration (400 ppm) both at 25 and 30 °C, especially at 0.95 a w . The multi-mycotoxin analysis performed by LC-MS/MS qTRAP showed a significant increase of deoxynivalenol and 15-acetyldeoxynivalenol production when the CH024b strain was exposed to elevated CO 2 compared to current CO 2 levels. Zearalenone production by the strain 0982 was significantly stimulated by mild water stress (0.95 a w ) and increased CO 2 concentration (1000 ppm) regardless of the temperature. Such results highlight that intraspecies variability exist among F. asiaticum strains with some mycotoxins likely to exceed current EU legislative limits under prospected climate change conditions., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Maize is the main staple food crop in the eastern part of Ethiopia. However, maize loss is a major issue due to fungal contamination especially at the post-harvest stage owing to inadequate handling practices. This study aimed to assess post-harvest handling and awareness against fungal development and fumonisin B 1 (FB 1 ) in maize and to calculate risk exposures of FB 1 . A total of 197 maize samples (grain and flour) were collected from five districts (Haramaya, Kersa, Meta, Oda Bultum, and Tullo). FB 1 was detected using LC-MS/MS qTRAP. Exposure assessment was done based on the maize consumption rate per day in Ethiopia for different age groups (infants, children, and adults). Risk characterization depends on the margin of exposure (MoE) combined with the lower confidence limit of the benchmark dose level (BMDL). About 81% of farmers were not physically separating undamaged maize ears with damaged from either birds or fungi. Moreover, 100% were not using improved storage material. In storage samples, FB 1 was detected as high as 1058 μg/kg ± 234 in the Kersa district while a minimum of 22.60 μg/kg ± 5.27 in Meta. In flour samples, the maximum FB 1 (327 μg/kg) was detected from the Oda Bultum district. The maximum exposure of infants was estimated at Kersa (1131 µg/kg bw/day), followed by Oda Bultum (1073 µg/kg bw/day) and Haramaya (854 µg/kg bw/day). Overall, FB 1 exposures ranged from 6.09 to 1131 µg/kg bw/day, which is 3 to 500 µg/kg bw/day higher than the maximum tolerable daily intake of 2 µg/kg bw/day recommended by the World Health Organization. The MoE ranged from 0.15 to 176, with infants being at higher risk than adults. The study highlights the urgent need to enhance growers' awareness and knowledge of good post-harvest practices to reduce mycotoxin contamination in maize. Further biomarker analysis must be pursued to determine the risk exposure assessment for different age groups in these areas with a priority for the Kersa district., (© 2022. The Author(s) under exclusive licence to Society for Mycotoxin (Research Gesellschaft für Mykotoxinforschung e.V.) and Springer-Verlag GmbH Germany, part of Springer Nature.)

The rapid detection of carbapenemase-producing microorganisms is crucial for clinical and infection control purposes. Here we evaluated Revogene®Carba C assay on 154 carbapenemase-producing and -nonproducing Gram-negatives. Up to 8 samples per 70 minutes were processed by Revogene®Carba C assay which showed excellent performances with 100% sensitivity, 99.5% specificity,100% NPV, and 97.8% positive predictive value., Competing Interests: Declaration of competing interests The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Ochratoxin A (OTA) is a well-known mycotoxin with wide distribution in food and feed. Fungal genome sequencing has great utility for identifying secondary metabolites gene clusters for known and novel compounds. A comparative analysis of the OTA-biosynthetic cluster in A. steynii, A. westerdijkiae, A. niger, A. carbonarius , and P. nordicum has revealed a high synteny in OTA cluster organization in five structural genes ( otaA , otaB, &nbsp; ota , otaR1 , and otaD ). Moreover, a recent detailed comparative genome analysis of Aspergilli OTA producers led to the identification of a cyclase gene, otaY , located in the OTA cluster between the otaA and otaB genes, encoding for a predicted protein with high similarity to SnoaLs domain. These proteins have been shown to catalyze ring closure steps in the biosynthesis of polyketide antibiotics produced in Streptomyces . In the present study, we demonstrated an upregulation of the cyclase gene in A. carbonarius under OTA permissive conditions, consistent with the expression trends of the other OTA cluster genes and their role in OTA biosynthesis by complete gene deletion. Our results pointed out the involvement of a cyclase gene in OTA biosynthetic pathway for the first time. They represent a step forward in the understanding of the molecular basis of OTA biosynthesis in A. carbonarius .

Three assays for SARS-CoV-2 antigen detection in nasopharyngeal swabs (Lumipulse® G SARS-CoV-2 Ag [LPG], STANDARD TM F COVID-19 Ag FIA [STF] and AFIAS COVID-19 Ag [AFC] were evaluated. Compared to RT-PCR, LPG, AFC and STF showed a variable sensitivity (87.9%, 37.5%, and 35.7%, respectively) and an overall high specificity (> 95%)., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Little is known on the impact that climate change (CC) may have on Aspergillus carbonarius and Ochratoxin A (OTA) contamination of grapes, especially in the Mediterranean region where in CC scenarios temperature are expected to increase by +2-5 °C and CO 2 from 400 to 800/1200 ppm. This study examined the effect of (i) current and increased temperature in the alternating 11.5 h dark/12.5 h light cycle (15-28 °C vs 18-34 °C), representative of the North Apulia area, South Italy and (ii) existing and predicted CO 2 concentrations (400 vs 1000 ppm), on growth, expression of biosynthetic genes (AcOTApks, AcOTAnrps, AcOTAhal, AcOTAp450, AcOTAbZIP) and regulatory genes of Velvet complex (laeA/veA/velB, "velvet complex") involved in OTA biosynthesis and OTA phenotypic production by three strains of A. carbonarius. The experiments made on a grape-based matrix showed that elevated CO 2 resulted in a general stimulation of growth and OTA production. These results were also supported by the up-regulation of both structural and regulatory genes involved in the OTA biosynthesis. Our work has shown for the first time that elevated CO 2 concentration in the Mediterranean region may result in an increased risk of OTA contamination in the wine production chain., (Copyright © 2019 British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

Ochratoxin A (OTA) is the primary mycotoxin threat in wine and dried vine fruits. Its presence in grape and wine is strongly related to climatic conditions and the expected climate change could represent a risk of increasing fungal colonization and OTA contamination in grapes. In this regard, the interacting effect of i) different conditions of water availability (0.93 and 0.99a w ) and ii) different 10 h/14 h dark/light alternating temperature conditions simulating a nowadays (18/31 °C) and climate change scenario (20/37 °C) in high OTA risk areas of Apulia region, were studied. Lag phases prior to growth, mycelial growth rate, the expression of biosynthesis, transcription factors and regulatory genes of OTA cluster and OTA production were analysed in Aspergillus carbonarius ITEM 5010 under the combined effect of different climatic factors. At 18/31 °C and under water stress conditions (0.93 a w ) the growth rate was slower than at 0.99 a w ; on the contrary, at 20/37 °C a higher growth rate was observed at 0.93 a w . An over-expression of OTA genes and genes belonging to the global regulator Velvet complex was observed at 18/31 °C and 0.99 a w , with the specific OTA pathway transcription factor bZIP showing the highest expression level. The up-regulated transcription profile of the genes positively correlated with OTA production higher at 18/31 °C than at 20/37 °C and 0.99 a w ; while no OTA production was detected at 0.93 a w at each of the temperature conditions tested. These findings provide preliminary evidence that the possible increase of the temperature, likely to happen in some areas of the Apulia region, may results in a reduction of both A. carbonarius spoilage and OTA production in grapes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: To establish the prevalence of the associated secondary diseases in patients with Raynaud's phenomenon (RP) attending a rheumatology specialty centre and to determine the frequency with which a secondary illness develops in those having RP, in absence of a well-defined secondary cause., Methods: 118 consecutive patients were evaluated. Medical history, physical and laboratory investigations entered into a database. Patients with primary RP and patients with RP who did not fulfil any diagnostic criteria for inclusion in a secondary form were followed up over a three-year period., Results: 63 RP patients were found with related conditions. 35 patients met criteria for inclusion in a primary RP group, 20 patients had 'unclassifiable' RP, of which two (10%) developed a well-defined disease. None of the primary RP patients developed a secondary disease., Conclusions: This study shows that less than 50% of patients with RP attending a rheumatology specialty centre have a connective tissue disease. Patients with isolated RP appear to have a benign disease, since primary RP remains as such, and only a small percentage of patients with 'unclassifiable' RP evolve into a well-defined CTD.

Objective: The aim of this pictorial essay is to show a representative example of sonographic-guided injection in carpal tunnel syndrome associated with tenosynovitis of the finger flexor tendons., Methods: Images were obtained using a real-time ultrasound system (AU4-idea; Esaote Biomedica, Genoa, Italy) equipped with a 13-MHz linear transducer. The best injection site was detected using a fine metal clip placed between the skin and the transducer. The images here were obtained in a patient with rheumatoid arthritis and carpal tunnel syndrome secondary to tenosynovitis of the finger flexor tendons., Results: Steroid injection within the carpal tunnel under sonographic control was easily performed. All steps of the needle placement within the widened tendon sheath were carefully evaluated on the monitor screen. Marked clinical improvement occurred shortly thereafter (3 days) and increased over the next 6 weeks., Conclusion: A detailed assessment of the carpal tunnel and a correct, safe placement of the needle for steroid injection can be quickly performed under sonographic guidance.

Objective: To show the most representative capillaroscopic findings in patients with systemic sclerosis (SSc)., Method: Capillaroscopic evaluation was performed with a videomicroscope at 100 times and 200 times magnification. Representative images of the nailbed microcirculation were obtained in 20 healthy subjects and in 75 patients with SSc., Results: Capillary abnormalities were seen at the nailfold in more than 90% of patients with SSc. Capillary involvement included several morphologic changes, which are easily distinguished from the pattern of healthy controls. Architectural disruption of the nailfold microvascular network, enlarged loops, neoformation of capillaries, loss of capillaries, and avascular areas are the main abnormalities detected in SSc patients., Conclusions: Nailfold capillary microscopy is one of the most valuable tools for the early diagnosis of SSc and related disorders. Rheumatologists and internists should be able to recognize these abnormalities because of their diagnostic relevance., (Copyright 2001 by W.B. Saunders Company)

Objective: To provide some representative examples of sonographically guided arthrocentesis and intralesional injection therapy., Methods: Sonographic evaluation was performed with high-frequency linear (13 MHz) and mechanical sector (20 MHz) transducers. The images were obtained in representative patients with rheumatoid arthritis and posttraumatic subacromial bursitis., Results: Sonographically guided intralesional injection is a rapid and reliable procedure, especially in patients with arthritis, tenosynovitis, and bursitis. After target localization, needle placement can be performed under continuous sonographic monitoring. Sonographic guidance is particularly useful when fluid collections are small (less than 5 mm) and deep or when the inflammatory process is adjacent to anatomic structures that could be seriously damaged by the injection., Conclusions: Over the last few years, the rapid technologic advancements in ultrasonography have dramatically increased the potential applications of sonographically guided procedures. The simplicity and reliability of the technique might warrant rheumatologists to undergo sonographic training.

Objective: To demonstrate the diagnostic efficacy of ultrasonography in depicting erosions in patients with rheumatoid arthritis and to compare sonographic and radiographic findings., Methods: Sonographic images were obtained with an AU-4 Idea Esaote Biomedica (Genoa, Italy) equipped with a 13 MHz linear transducer., Results: The images reported in this essay are representative examples of the ability of ultrasonography to detect and characterise even minimal bone margin changes in rheumatoid arthritis., Conclusion: Ultrasonography with very high frequency transducers can depict bone erosions in early target areas of bone resorption. However, further studies are needed to validate this technique and to evaluate the relation between sonographic findings and those obtained with other imaging techniques (standard radiology, magnetic resonance).

Objective: To evaluate the relative roles of endothelium and platelets in the pathogenesis of primary RP and RP secondary to SSc., Methods: Endothelial derived ET-1, t-PA, PAI-1, and platelet derived beta-TG, PDGF, TGF-beta were measured in 36 patients with primary RP, 14 patients with RP secondary to SSc and 30 age and sex matched controls., Results: A significative increase of ET-1, t-PA, PAI-1, TGF-beta, and beta-TG were the most relevant changes in patients with RP secondary to SSc with respect to the controls. Less relevant increases of t-PA, PAI-1, PDGF, and beta-TG levels were observed in patients with primary RP vs controls., Conclusions: These data seem to confirm the involvement of endothelial cells and platelets in the pathogenesis of RP, with mild changes in primary RP and more relevant changes in RP secondary to SSc.

Objective: To investigate the potential role of ultrasonography (US) with very high frequency transducers in assessing distal phalanx involvement in some rheumatic diseases., Methods: We performed sonographic evaluation with an Esaote AU-4 Idea (Esaote Biomedica, Genoa, Italy) equipped with a 13-MHz linear transducer. The images were obtained in asymptomatic healthy subjects and representative patients with psoriatic arthritis, osteoarthritis of the distal interphalangeal joint (Heberden's nodes), erosive osteoarthritis, gout, rheumatoid arthritis, systemic sclerosis, and posttraumatic synovial cyst., Results: US with very high frequency transducers allowed a careful identification of the following anatomic details: joint space, extensor and flexor tendons, bone margin, periarticular and peritendinous soft tissues, nail, and blood vessels. Several pathological changes were depicted in different rheumatic disorders. These included joint space widening, tendon sheath widening, dislocation of the joint surfaces, irregularity of the bone margin, and urate and calcium deposits within periarticular soft tissues., Conclusions: Very high frequency US is able to depict the anatomic substrate of distal phalanx involvement in several rheumatic diseases, adding useful information to clinical examination of the hand.

Objective: The aim of this pictorial essay is to describe the sonographic guided approach to investigation and local injection therapy of a small joint in a patient with psoriatic arthritis (PA)., Methods: Sonographic pictures are obtained using a high frequency ultrasonography apparatus equipped with a 13-MHz transducer., Results: Ultrasonography allows a careful morphostructural assessment of soft tissue involvement in PA patients. Sonographic findings include joint cavity widening, capsular thickening, synovial proliferation, synovial fluid changes, tendon sheath widening. Ultrasound guided placement of the needle within the joint and injection of corticosteroid under sonographic control can be easily performed., Conclusions: High frequency ultrasonography is a quick and safe procedure that allows a useful diagnostic and therapeutic approach in patients with arthritis of small joints.

Objectives: This study was undertaken to describe representative sonographic features of normal and osteoarthritic cartilage., Methods: Sonographic evaluation was performed with real-time ultrasound equipment, using 7.5-, 10-, 13-, 15-, and 20-MHz transducers. Normal and osteoarthritic cartilage has been studied in healthy subjects and in patients with osteoarthritis., Results: Ultrasonography allows a safe, quick, and careful evaluation of both normal and osteoarthritic cartilage. A spectrum of images ranging from loss of cartilage transparency to marked narrowing of the cartilage layer can be depicted clearly in patients with osteoarthritis. Loss of clarity of the cartilaginous band and loss of the normal sharpness of the synovial space-cartilage interface are the earlier features of cartilage damage., Conclusions: Although the value of ultrasonography in the evaluation of articular cartilage remains to be determined, this imaging method can be regarded as a useful bedside procedure for initial diagnostic screening of osteoarthritic femoral condylar cartilage.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by progressive damage of synovial-lined joints and variable extra-articular manifestations. Tendon and bursal involvement are frequent and often clinically dominant in early disease. RA can affect any joint, but it is usually found in metacarpophalangeal, proximal interphalangeal and metatarsophalangeal joints, as well as in the wrists and knee. Articular and periarticular manifestations include joint swelling and tenderness to palpation, with morning stiffness and severe motion impairment in the involved joints. The clinical presentation of RA varies, but an insidious onset of pain with symmetric swelling of small joints is the most frequent finding. RA onset is acute or subacute in about 25% of patients, but its patterns of presentation also include palindromic onset, monoarticular presentation (both slow and acute forms), extra-articular synovitis (tenosynovitis, bursitis), polymyalgic-like onset, and general symptoms (malaise, fatigue, weight loss, fever). The palindromic onset is characterized by recurrent episodes of oligoarthritis with no residual radiologic damage, while the polymyalgic-like onset may be clinically indistinguishable from polymyalgia rheumatica in elderly subjects. RA is characteristically a symmetric erosive disease. Although any joint, including the cricoarytenoid joint, can be affected, the distal interphalangeal, the sacroiliac, and the lumbar spine joints are rarely involved. The clinical features of synovitis are particularly apparent in the morning. Morning stiffness in and around the joints, lasting at least 1 h before maximal improvement is a typical sign of RA. It is a subjective sign and the patient needs to be carefully informed as to the difference between pain and stiffness. Morning stiffness duration is related to disease activity. Hand involvement is the typical early manifestation of rheumatoid arthritis. Synovitis involving the metacarpophalangeal, proximal interphalangeal and wrist joints causes a characteristic tender swelling on palpation with early severe motion impairment and no radiologic evidence of bone damage. Fatigue, feveret, weight loss, and malaise are frequent clinical signs which can be associated with variable manifestations of extra-articular involvement such as rheumatoid nodules, vasculitis, hematologic abnormalities, Felty's syndrome, and visceral involvement. Although there is no laboratory test to exclude or prove the diagnosis of rheumatoid arthritis, several laboratory abnormalities can be detected. Abnormal values of the tests for evaluation of systemic inflammation are the most typical humoral features of RA. These include: erythrocyte sedimentation rate, acute phase proteins and plasma viscosity. Erythrocyte sedimentation rate and C-reactive protein provide the best information about the acute phase response. The C-reactive protein is strictly correlated with clinical assessment and radiographic changes. Plain film radiography is the standard investigation to assess the extent of anatomic changes in rheumatoid arthritis patients. The radiographic features of the hand joints in early disease are characterized by soft tissue swelling and mild juxtaarticular osteoporosis. In the the past 10 years, ultrasonography has gained acceptance for studying joint, tendon and bursal involvement in RA. It may improve the early clinical assessment and the follow-up of these patients, showing such details as synovial thickening even within finger joints. Other imaging techniques, such as magnetic resonance, computed tomography and scintigraphy may provide useful information about both the features and the extent for anatomic damage in selected rheumatoid arthritis patients. The natural history of the disease is poorly defined; its clinical course is fluctuating and the prognosis unpredictable. RA is an epidemiologically relevant cause of disability. An adequate early treatment of RA may alter the diseas

Eighteen non-smoking women suffering from primary Sjögren's syndrome (pSS) with previously documented alveolitis were re-examined, clinically and by pulmonary function tests (PFT), bronchoalveolar lavage (BAL), chest X-ray and high-resolution computed tomography (HRCT) after a 2 yr follow-up period. Longitudinal evaluation revealed unchanged PFT. The final BAL study showed a normal differential count in six of 14 patients with initial lymphocyte alveolitis, and a persistent alveolar lymphocytosis in the remaining eight patients, associated with an increased percentage of neutrophils in one of them. In four patients with initial mixed alveolitis, the BAL cell profile was unchanged 2 yr later. Five of 18 patients (28%) had abnormal HRCT, represented by isolated septal/subpleural lines in three patients, ground-glass opacities with irregular pleural margins in one patient, and ground-glass opacities associated with septal/subpleural lines in another. All these patients had abnormal BAL results with an increased proportion of both neutrophils and lymphocytes. The presence of alveolar neutrophils was associated with a significantly (P=0.005) greater mean rate of reduction of carbon monoxide diffusing capacity (DLCO) -- more than four times the normal rate of loss of DLCO. Chest X-ray, repeated at the end of the 2 yr follow-up period, showed parenchymal abnormalities in only one patient who had evidence of fibrosis on HRCT. This study provides evidence that lung involvement is not an uncommon extraglandular manifestation of pSS and that a BAL neutrophilia may play an important role in the pathogenesis of pulmonary disease in this autoimmune disorder.

Corticosteroid usage was assessed in rheumatoid arthritis (RA) and psoriatic arthritis (PA) patients in Italy. A multicentre, observational study was undertaken in 10 Italian rheumatological centres from 1990 to 1992 using a computerised clinical data bank. Nine hundred and seven RA patients and 180 PA patients were studied; 510 (56.2%) RA patients and 44 (24.4%) PA patients were using corticosteroids. The percentage of patients taking corticosteroids ranged from 20.5 to 85.4% for RA patients and from 0 to 55% for PA patients for the different centres. Methylprednisolone was the most prescribed corticosteroid, both in RA patients (63.2%) and in PA patients (65.9%). The average methylprednisolone daily dose was 5.7+/-3.6 mg in RA patients and 4.5+/-1.4 mg in PA patients. The data provide evidence that corticosteroids are taken in an unexpectedly high percentage of patients with RA and PA in Italy.

Pneumonitis is emerging as one of the most unpredictable and potentially serious, adverse effects of treatment with MTX. Its prevalence in rheumatoid arthritis (RA) has been estimated from several retrospective and prospective studies to range from 0.3% to 18%. On the other hand, MTX-induced pneumonitis seems to be very rare in psoriatic arthritis (PsA). Our review of 194 RA patients and 38 PsA patients receiving MTX has identified four RA patients and one PsA patient with MTX-induced pneumonitis, giving a prevalence of 2.1% and 0.03%, respectively. Diagnosis was suggested by clinical history and radiographic findings, but the bronchoalveolar lavage plays an important role both in excluding infectious agents and in providing information for understanding the pathogenesis of lung injury. The presence of a lymphocyte alveolitis with a predominance of CD4+ T cells in 3 RA patients and CD8+ T cells with a concomitant increase in neutrophils in another case suggests that immunologically mediated reactions may be one damage mechanism in MTX-induced pneumonitis. Although risk factors for MTX-induced pulmonary toxicity are poorly understood, the presence in 3 out of 5 of our patients of pre-existing lung disease, represented by diffuse interstitial changes on chest X-ray, and mild bronchial asthma in two RA patients and by pulmonary silicosis in the patient with PsA may account for a predisposition to the development of MTX pneumonitis.

Non-steroidal anti-inflammatory drugs (NSAIDs) give rise to a wide range of gastrointestinal side-effects. These are reviewed and it is stressed that some safety measures are possible only if the risk factors are considered. The relations between dyspeptic symptoms and gastrointestinal lesions are also debated. It is suggested that the ulcerogenic potential of various molecules must be carefully evaluated, especially in elderly patients.

In order to evaluate the presence of an inflammatory process of the lower respiratory tract in patients with mixed cryoglobulinaemia (MC) associated with hepatitis C virus (HCV), bronchoalveolar lavage (BAL) was performed in 16 non-smoking females free of clinical pulmonary symptoms and with normal chest roentgenograms. Pulmonary function tests including diffusion capacity for carbon monoxide (DLCO) were also carried out. Thirteen healthy subjects were evaluated as the control group. Patients with MC had a lower percentage of alveolar macrophages (75% vs 92%, P = 0.001) and a higher percentage of lymphocytes (19.7% vs 7%, P = 0.001) than healthy controls. The percentage of CD3+ lymphocytes was higher in MC patients than in controls (86.5% vs 70%, P = 0.004). No significant differences in the percentage of CD4+, CD8+ and CD19+ lymphocytes, neutrophils and eosinophils were found. Pulmonary function tests showed significantly lower values of forced expiratory flow (FEF) 25-75 (P = 0.05) and DLCO (P = 0.05) in MC patients than in healthy controls. No correlations between BAL results and pulmonary function tests were found. The 5 yr follow-up of five patients did not demonstrate deterioration in lung function. Thus, BAL results indicate a subclinical T-lymphocytic alveolitis in MC HCV+ patients that is not associated with a risk of deterioration in lung function.

Hypertrophic osteoarthropathy (HOA) is characterized by finger clubbing, periostosis and arthritis. The pathogenesis of hypertrophic osteoarthropathy is still uncertain. Earlier studies have been focused on the potential role of platelet and endothelium in the pathogenesis of HOA. The aim of this study was to evaluate the circulating levels of endothelin-1 (ET-1), beta-thromboglobulin (beta-TG) and platelet-derived growth factor (PDGF) in 21 HOA patients. The circulating levels of ET-1, beta-TG were significantly higher in HOA patients vs healthy controls, but not vs controls with lung diseases. On the contrary, PDGF was significantly higher in HOA patients vs healthy controls and vs subjects with lung diseases. These findings suggest that "endothelium/platelet unit" may play a role in the pathogenesis of HOA, and PDGF could induce the changes observed in HOA.

Objective: The effect of recombinant interferon alpha-2 (IFN alpha 2) therapy in Sjögren's syndrome (SS) was studied., Methods: An open study was performed in which 20 SS patients were given IFN alpha 2 3.10(6) MU/3 times/week or OH-chloroquine (OH-C) 6 mg/kg/daily, for a mean period of 11 months., Results: Gland assessment showed that lacrimal and salivary function improved by 67% and 61% versus 15% and 18% respectively (p < 0.01) in the patients treated with IFN alpha 2 compared to those treated with OH-C. Immunological parameters did not change over time in either group. In 3 patients a decrease in the tissue score was observed in the IFN alpha 2 group, while no changes were seen in the control group. Tolerability was acceptable., Conclusion: This study shows that IFN can improve tear function and dry mouth in SS, without causing significant side effects.

We evaluated the efficacy and toxicity of cyclosporine A (CsA) in combination with methotrexate (MTX) or hydroxychloroquine (HCQ) in patients with refractory rheumatoid arthritis (RA). Fourteen patients with active RA who had failed to respond adequately to injectable MTX and 14 who had failed to respond to oral HCQ had CsA added to their regimens for 6 months. Adverse effects were monitored every 2 weeks for 2 months, and monthly thereafter; outcome parameters were assessed at 0, 3, and 6 months. The starting dose of CsA was 2.5 mg/kg/day in both groups. Twenty-four patients (12 in each group) completed the 6-month study. All clinical variables (except grip strength in the HCQ + CsA group) significantly improved with both treatment regimens. Global efficacy was evaluated by means of the composite Chronic Arthritis Systemic Index. Fifteen patients (9 in the MTX + CsA and 6 in the HCQ + CsA group) could be considered responders, and 9 non-responders. The final mean daily dose of CsA was 3.3 +/- 0.8 mg/kg in the HCQ + CsA group and 3.1 +/- 0.9 mg/kg in the MTX + CsA group. Mild adverse events were more frequently observed in the MTX-CsA than in HCQ + CsA-treated patients (33 events in 11 patients as against 20 in nine). In combination with HCQ or MTX, CsA, over a 6 month period, may improve efficacy in patients with refractory RA without any significant increase in toxicity; MTX + CsA seems to be slightly more efficacious and more toxic than HCQ + CsA. Larger prospective controlled trials are necessary to define the efficacy of these combinations.

The aim of this study was to assess the correlations of the serum soluble interleukin 2 receptor (sIL-2R) concentrations with disease activity parameters and response to treatment with second line drugs in patients with rheumatoid arthritis (RA). Sixty-seven patients with active disease completed a 24-week, open, randomized study of methotrexate (MTX) versus sulphasalazine (SSZ) or hydroxychloroquine (HCQ). Serum sIL-2R levels were evaluated before entry and after 24 weeks by ELISA. Serum sIL-2R were significantly higher in RA patients than in controls (P = 0.0001) and correlated significantly only with erythrocyte sedimentation rate (P = 0.03) and with Chronic Arthritis Systemic Index (P = 0.01) at study entry. No correlation was found between serum sIL-2R and other laboratory and clinical indices of disease activity. After 24 weeks of treatment no differences in serum sIL-2R in comparison with basal levels were found in either responding or in non-responding patients, although the mean reduction of sIL-2R was more marked in the MTX-treated cohort than in the HCQ and SSZ-treated groups. These data suggest that in RA the measurement of sIL-2R should be used with caution as an isolated index of disease activity and that it is not a useful marker of response to treatment with second line drugs.

Objective: To characterize finger tendon involvement in patients with rheumatoid arthritis (RA)., Methods: The finger tendons of 20 RA patients were studied by ultrasonography using a high-frequency (13-MHz) transducer., Results: Eighteen patients (90%) showed finger tendon abnormalities: widening of the flexor tendon sheath (80%), loss of the normal fibrillar echotexture (60%), irregularity of the extensor (30%) and flexor (50%) tendon margins, tendon tear (10%), synovial cyst (20%)., Conclusion: High-frequency sonography is helpful in assessing even minimal finger tendon lesions in RA patients.

It has been demonstrated that the calcium antagonist nifedipine inhibits the reactive oxygen species (ROS) production by polymorphonuclear leucocytes (PMNLs) activated with phorbol myristate acetate (PMA), but the mechanism underlying this effect is still unknown. In the present study we investigated the influence of nifedipine on the PMNL plasma membrane using 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5,hexatriene (TMA-DPH) fluorescence polarization (P) and on PMA- and N-formyl-methionyl-leucyl-phenylalanine (FMLP)-induced ROS production, measured by luminol-dependent chemiluminescence (CL). The plasma membrane fluidity of untreated PMNLs, expressed as P, was 0.371 +/- 0.008. After preincubation of 15 min, nifedipine induced a significant change in P values only at a concentration of 10(-4) M (P = 0.00018). After preincubation of 60 min significant changes in P values were also observed at concentrations of 10(-6) M (P = 0.023) and 10(-7) M (P = 0.023). PMA-induced ROS production by PMNLs was markedly inhibited by nifedipine. Nifedipine also determined a striking change in the FMLP-induced CL response, characterized by both an overall inhibition of PMNL activity and a modification of the kinetics of the oxidative burst (rapid increase in ROS production followed by a pronounced drop in the PMNL response). Such a pattern was found at concentrations of 10(-4) M (preincubation time: 15 min), 10(-6) M and 10(-7) M (preincubation time: 60 min). These findings indicate that nifedipine directly interacts with the PMNLs by inducing a marked decrease in plasma membrane fluidity and an inhibition of the oxidative burst.

Objective: To determine the long-term efficacy and safety of weekly low-dose methotrexate (MTX) in rheumatoid arthritis (RA)., Methods: Fifty-one patients receiving MTX for RA were prospectively studied over a mean treatment period of 36 months. Standard clinical and laboratory measures of disease activity were assessed by the same investigator at baseline, and at 3, 6, 12, 24 and 36 months., Results: The overall probability of continuing to take MTX was 80.3% at 12 months, 74.5% at 24 months, and 70.5% at 36 months. Of the 36 patients who completed 36 months of therapy, a significant improvement was noted compared to baseline in all of the clinical disease variables and acute phase reactants, with a steroid-sparing effect. There were no significant differences in these parameters between the 36-month visit and the 24- or 12-month visit. Adverse events occurred frequently (80.3%), but only 15.6% of the patients discontinued MTX permanently. Four patients (7.9%) withdrew due to a lack of efficacy., Conclusion: Our findings indicate that MTX remains effective over 36 months of therapy, with an acceptable toxicity profile.

Calcium-channel blockers are widely used in the treatment of systemic sclerosis (SSc), but their in vivo influence on microcirculation is not fully elucidated. We evaluated the acute effect of nifedipine on the cold-induced changes of microvascular dynamics in SSc. Eleven SSc patients and seven healthy volunteers were studied. Dynamic aspects of the nailfold microcirculation (appearance time at the nailfold, transcapillary diffusion, interstitial distribution and interstitial clearance of sodium fluorescein given i.v.) were quantitatively assessed by a computer-aided fluorescence videomicroscope. Fluorescent light intensities (FLIs) at predefinite pericapillary and interstitial sites were measured under three experimental conditions: (1) baseline; (2) after cold test; (3) after single oral administration of 10 mg of nifedipine 5 min before cold exposure. The interval between the intravenous injection of sodium fluorescein and the first appearance of the dye at the nailfold significantly increased after cold exposure in the SSc patients (224.1 +/- 182.3 s vs 27.5 +/- 25.1 s at baseline) (P = 0.0026), but not in the controls (28.0 +/- 13.3 s vs 29.6 +/- 12.4 s at baseline). The effect of cold exposure on the appearance of the dye was not significantly antagonized by nifedipine (112.7 +/- 91.8 s) in the SSc patients (P = 0.07). Cold exposure significantly decreased transcapillary diffusion and interstitial distribution of sodium fluorescein in the SSc patients (P < 0.016), but not in the controls. The cold-induced changes of FLI values were antagonized by nifedipine in the SSc patients (P < 0.016), but not in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: Obesity is often associated with knee osteoarthritis (OA) and with chronic hyperinsulinemia. The aim of our study was to investigate the relationship between overweight patients and OA of the knee., Methods: Forty-eight overweight outpatients (40 women and 8 men) were recruited into the study. They were separated into 2 groups: Group 1 patients with OA of the knee and Group 2 subjects without OA of the knee. Serum insulin levels were determined in all patients., Results: Insulin levels were statistically higher in patients with OA (p < 0.01) compared to subjects without OA., Conclusion: Our data suggest that insulin may play a role in the pathogenesis of OA of the knee in overweight patients.

Objective: To determine whether the first order kinetics model or the function proportional to the square root of disease duration better represents the progression of radiographic damage according to the disease duration than a linear model in rheumatoid patients., Methods: Two hundred twenty-eight patients assessed at a single time point were studied by using 2 nonlinear models of radiographic damage. In 44 patients a second radiographic analysis was taken within a 3-year period., Results: In this data set, both models reveal the highest rate of progression in the first 3 years of the disease. The square root of the disease duration seems to better depict the whole disease course., Conclusion: Nonlinear models should be compulsory in the assessment of radiographic damage, especially when slow acting antirheumatic drug effects after 5 years of disease duration are studied.

Objective: To examine capillary permeability in fibromyalgia (FMS) we studied the nailfold capillaries of 13 unselected patients with FMS and 9 healthy controls using dynamic fluorescence videomicroscopy., Methods: The transcapillary permeability of a 20% solution of sodium fluorescein injected into an antecubital vein was assessed by videodensitometric analysis. The pericapillary and interstitial fluorescent light intensities (FLI) were calculated at different sites on a transverse axis crossing the selected capillary., Results: Fluorescence videomicroscopy revealed no abnormalities in the pattern of dye distribution around the nailfold capillaries in the patient group. Videodensitometric analysis showed a trend to an increased early transcapillary diffusion in patients with FMS, but the difference was only significant at 3 s from the first appearance of the dye (p < 0.05). From 10 s to 1 min after the dye's appearance, the mean FLI in the patients equalled that of the controls. The patients with FMS showed an earlier but lower FLI peak. Moreover, the FLI were significantly lower in the patients than in the controls from 5 to 30 min after the dye appearance in all of the sites of the densitometric analysis (p < 0.05). Thirty min after the first appearance of the dye, the FLI was reduced by more than 50% in the patient group compared to the controls., Conclusion: Our results indicate that transcapillary permeability and the interstitial persistence of the tracer in FMS are significantly reduced compared to controls. This difference may be caused by the abnormal microvascular dynamics induced by low capillary flow and/or capillary bed hypotension.

Objective: To determine the influence of cold exposure on microvascular permeability in systemic sclerosis (SSc)., Methods: Thirteen patients with SSc were studied by dynamic fluorescence videomicroscopy under basal conditions and after exposure to cold., Results: Exposure to cold caused a significant reduction in the interstitial concentration of sodium fluorescein (P < 0.05 to 0.001)., Conclusion: Our findings show that cold exposure has a striking effect on microvascular dynamics in SSc.

The prevalence of Raynaud's phenomenon in RA was retrospectively reviewed in 411 consecutive RA patients and in a control group of 919 consecutive outpatients with OA. Raynaud's phenomenon was found in 19 (4.6%) of 411 RA patients and in 52 (5.6%) of 919 patients with OA: its prevalence was 4.3% (13 cases) in RA inpatients and 5.4% (six cases) in RA outpatients. Among the RA patients, the prevalence of Raynaud's phenomenon was 7.5% in men (7% of inpatients, 8.8% of outpatients) and 3.2% in women (3% of inpatients, 3.9% of outpatients) (P = N.S.). Conversely, the prevalence of Raynaud's phenomenon in patients with OA was higher in women (6.5%) than in men (2.9%) (P = 0.045). Our study indicates that the reported association between Raynaud's phenomenon and RA cannot be confirmed on the basis of a retrospective assessment of its prevalence.

This study reports psychological symptoms assessed in 327 patients with fibromyalgia (FS) in a multicenter investigation. Two self-report scales, in their validated Italian translations, were used for screening: the CES-D (the Center of Epidemiologic Studies-Depression) developed at the NIMH for measuring depression and the Illness Behavior Questionnaire (IBQ) developed by Pilowsky and Spence. The cutoff point of 23 in the CES-D scores revealed about 49% of the fibromyalgic patients as depressed. In analyzing patterns of illness behavior patients with FS showed a high score on IBQ scales of disease conviction, psychological versus somatic focusing and denial. CES-D scores showed significant correlations with illness behavior scales. These results and their implications for the treatment of fibromyalgic patients are discussed.

The measurement of serum soluble interleukin-2 receptor (sIL-2R), a sensitive marker of lymphocyte activation, has been proposed as an indicator of disease activity and "outcome" in patients with inflammatory diseases characterized by the activation of immune cells. Serum sIL-2R levels have been reported higher in rheumatoid patients than in controls. Using an enzyme-linked immunoabsorbent assay (ELISA), we evaluated soluble IL-2R levels in the serum of 34 patients with RA and in the synovial fluid of 25 of these patients and we compared it with levels found in the serum of 13 healthy controls. Serum sIL-2R levels were significantly elevated in RA patients compared with the healthy age-matched control group (P < 0.005). The mean level of soluble IL-2R in synovial fluids was significantly higher than the mean sera levels in RA patients (P < 0.0001). Moreover, we examined the correlation between serum and synovial fluid sIL-2R levels and disease activity measures. Serum sIL-2R correlated only with ESR (P < 0.04). The synovial fluid sIL-2R correlated with ESR (P < 0.02) and a visual analogue scale (VAS) pain score (P < 0.04). Both serum and synovial fluid sIL-2R levels correlated with the chronic arthritis systemic index (CASI; P < 0.04 and P < 0.005, respectively). Our data suggested that in RA the measurement of sIL-2R may certainly mirror the degree of chronic inflammation and the continuous activation of the immune cells in the joint, although the role of this molecule in the immune response is still unclear.

Recently somatostatin (SST) intra-articular administration has been used in the treatment of some rheumatoid diseases such as rheumatoid arthritis, psoriatic arthritis and osteoarthritis with encouraging results. The aim of this study was to evaluate the efficacy and tolerability of SST intra-articularly injected, involving 20 patients with knee osteoarthritis. Treatment consisted of 4 injections, administered weekly, each of 750 mcg SST. Additionally, in six of them we evaluated the circulating levels of the insulin-like growth factor (IGF)-1 at the base-line time and then every 7 days (immediately before each dose of SST). The results revealed an improvement in pain and in joint function after intra-articular SST, confirmed by statistical analysis. The circulating levels of IGF-1 did not show significant variations following intra-articular administration of SST. The excellent tolerability and the absence of unwanted side-effects with SST allow us to foresee that intra-articular SST could be used in cases of painful knee osteoarthritis, especially in those patients in which other drugs are not appropriate. Moreover, in the absence of modifications of serum levels of IGF-1, SST could be used in athletes.

Reported here are the results of a study carried out in order to assess the possible influence of the major circulating active metabolite of nabumetone, 6-methoxy-2-naphthylacetic acid, on some aspects of polymorphonuclear leukocytes activation. The action of 6-methoxy-2-naphthylacetic acid was tested on the following features of polymorphonuclear leukocytes activation: reactive oxygen species production in polymorphonuclear leukocytes stimulated with different agonists, reactive oxygen species production in polymorphonuclear leukocytes treated with pertussis toxin, NADPH-oxidase activity. The findings showed that 6-methoxy-2-naphthylacetic acid decreased reactive oxygen species production in polymorphonuclear leukocytes stimulated with N-formyl-methionyl-leucyl-phenylalanine, phorbol myristate acetate, and opsonized zymosan, but failed to provoke a decrease of reactive oxygen species production when the cells were stimulated with calcium ionophore A23187. Moreover, 6-methoxy-2-naphthylacetic acid did not influence the transduction of the signal following the binding of stimuli to membrane receptors, and NADPH-oxidase activity. Finally, our findings showed that 6-methoxy-2-naphthyl acetic acid had no scavenger effect on reactive oxygen species production.