Ultra-wide-field fundus photography compared to ophthalmoscopy in diagnosing and classifying major retinal diseases.

To analyze the performance of ultra-wide-field (UWF) fundus photography compared with ophthalmoscopy in identifying and classifying retinal diseases. Patients examined for presumed major retinal disorders were consecutively enrolled. Each patient underwent indirect ophthalmoscopic evaluation, with scleral depression and/or fundus biomicroscopy, when clinically indicated, and mydriatic UWF fundus imaging by means of CLARUS 500™ fundus camera. Each eye was classified by a clinical grader and two image graders in the following groups: normal retina, diabetic retinopathy, vascular abnormalities, macular degenerations and dystrophies, retinal and choroidal tumors, peripheral degenerative lesions and retinal detachment and myopic alterations. 7024 eyes of new patients were included. The inter-grader agreement for images classification was perfect (kappa = 0.998, 95% Confidence Interval (95%CI) = 0.997-0.999), as the two methods concordance for retinal diseases diagnosis (kappa = 0.997, 95%CI = 0.996-0.999) without statistically significant difference. UWF fundus imaging might be an alternative to ophthalmoscopy, since it allows to accurately classify major retinal diseases, widening the range of disorders possibly diagnosed with teleophthalmology. Although the clinician should be aware of the possibility that a minority of the most peripheral lesions may be not entirely visualized, it might be considered a first line diagnostic modality, in the context of a full ophthalmological examination.

[Italian Society of Rheumatology (SIR) recommendations for performing arthrocentesis]. / Raccomandazioni della Società Italiana di Reumatologia per l'esecuzione dell'artrocentesi.

Joint fluid aspiration, or arthrocentesis, is one of the most useful and commonly performed procedures for the diagnosis and treatment of rheumatic diseases, but to date no definite guidelines have been published. For this reason, a group of experts of the Italian Society of Rheumatology (SIR) produced evidence based recommendations for performing arthrocentesis. Among them, the most relevant are: a) arthrocentesis is necessary when synovial effusion of unknown origin is present, especially if septic or crystal arthritis is suspected; b) the patient should be clearly informed of the benefits and risks of the procedure in order to give an informed consent; c) ultrasonography should be used to facilitate arthrocentesis in difficult joints; d) fluid evacuation often has a therapeutic effect and facilitates the success of the following intraarticular injection; e) careful skin disinfection and the use of sterile, disposable material is mandatory for avoiding septic complications. Disposable, non sterile gloves should always be used by the operator, mainly for his own protection; f) contraindications are the presence of skin lesions or infections in the area of the puncture; g) the patient's anticoagulant treatment is not a contraindication, providing the therapeutic range is not exceeded; h) joint rest after arthrocentesis is not indicated. Several of these recommendations were based on experts' opinion rather than on published evidence which is scanty.

Synovial expression of vasoactive intestinal peptide in polymyalgia rheumatica.

OBJECTIVE: Polymyalgia rheumatica (PMR) is an inflammatory disease that typically affects elderly people. Its clinical hallmark is the severity of pain in the shoulder and pelvic girdle. Mild to moderate synovitis and/or bursitis of the joints involved has been described. Neuropeptides are involved in nociception and modulation of inflammatory reaction. To evaluate whether neuropeptides have a role in PMR pathophysiology, we studied the expression of substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and somatostatin (SOM) in shoulder synovial tissues of PMR patients. METHODS: Synovial expression of neuropeptides was investigated by immunohistochemical analysis, in two groups of PMR patients: the first one at the onset of disease and the second one after corticosteroid treatment, and in other joint diseases, rheumatoid arthritis (RA) and osteoarthritis (OA). RESULTS: The only significant expression of VIP was found in PMR and, to a lesser extent, in RA synovial tissue. In PMR, we observed VIP immunostaining both in the lining layer and in the sublining area. In patients on corticosteroid treatment VIP lining layer expression was not significantly different while VIP positive cells in the sublining area were almost absent. CONCLUSION: Local VIP production in PMR synovial tissue might contribute to the typical musculoskeletal discomfort and it may have a role in the immunomodulation of synovial inflammation.

[Italian consensus on EULAR recommendations 2005 for the management of hip osteoarthritis]. / Consensus italiana sulle raccomandazioni EULAR 2005 per il trattamento dell'artrosi dell'anca.

The recommendations for the management of osteoarthritis (OA) of the hip were proposed by EULAR in 2005. Among the most important objectives of the expert charged to provide these recommendations were their wide dissemination and implementation. Thus, the information generated can be used by each individual country to produce their own set of management guidelines and algorithms for treatment in primary care. According with that previously executed for the EU-LAR recommendation 2003 for the knee, the Italian Society of Rheumatology (SIR) has organised a Consensus on the EULAR recommendations 2005 for the management of hip OA. To obtain an acceptability as large as possible, the group of experts was composed by many physicians interested in the management of hip OA, including Orthopaedics, Rheumatologists, Physiatrists, and General Practitioners. Main aim of the Consensus was to analyse the acceptability and applicability of the recommendations according to own experience and local situations in the Italy. The results of this Consensus have demonstrated that a large majority of the EULAR recommendations are endorsed by the Italian experts. Furthermore, the final document of the Italian Consensus clearly indicated the need that the specialists involved in the management of hip OA strongly encourage the dissemination of the EULAR 2005 recommendations also in Italy.

Vascular endothelial growth factor activities on osteoarthritic chondrocytes.

OBJECTIVE: Evaluation of the role of VEGF in cartilage pathophysiology. METHODS: VEGF release from chondrocytes in the presence of IL-1beta, TGFbeta and IL-10 was detected by immunoassay. VEGF receptor -1 and -2 expression and VEGF ability to modulate caspase -3 and cathepsin B expression were detected by immunohistochemistry on cartilage biopsies and cartilage explants. VEGF effects on chondrocyte proliferation was analysed by a fluorescent dye that binds nucleic acids. RESULTS: VEGF production by osteoartritis (OA) chondrocytes was significantly reduced by IL-1beta while it was increased in the presence of TGFbeta. Cartilage VEGFR-1 immunostaining was significantly downregulated in 'early' OA patients compared to normal controls (NC). VEGFR-2 expression was negligible both in OA and in NC. VEGF decreased the expression of caspase-3 and cathepsin B, whereas it did not affect proliferation. CONCLUSION: VEGF is able to down-modulate chondrocyte activities related to catabolic events involved in OA cartilage degradation.

[Italian consensus on Eular 2003 recommendations for the treatment of knee osteoarthritis]. / Consensus italiana sulle raccomandazioni dell'EULAR 2003 per il trattamento dell'artrosi del ginocchio.

The recommendations for the management of osteoarthritis (OA) of the knee firstly proposed by the EULAR in 2000, have been updated in 2003. One of the most important objectives of the expert charged to provide these recommendations was their dissemination. Thus, the information generated may be used by each individual country to produce their own set of management guidelines and algorithms for treatment in primary care. The Italian Society of Rheumatology (SIR) and the Italian League against Rheumatism (LIMAR) have organised a Consensus on the EULAR recommendations 2003 with the aim to analyse their acceptability and applicability according to our own experience and local situations in the Italy. The results of this Consensus have demonstrated that a large majority of the EULAR recommendations are endorsed by the Italian experts. Furthermore, the final document of the Italian Consensus clearly indicated the need that specialists involved in the management of knee OA strongly encourage the dissemination of the EULAR 2003 recommendations also in Italy.

[Pain patterns in Italian patients with osteoarthritis: preliminary results of the MI.D.A. Study (Misurazione del Dolore nell'Artrosi)]. / Caratteristiche del dolore in pazienti italiani con artrosi: risultati preliminari dello Studio MI.D.A. (Misurazione del Dolore nell'Artrosi).

OBJECTIVES: To evaluate the characteristics of pain in a cohort of Italian patients with osteoarthritis (OA) of the hip and knee. METHODS: The 657 general practitioners participating in the study were asked to enroll 10 consecutive patients with OA diagnosed according to the American College of Rheumatology (ACR) clinical criteria. A questionnaire evaluating demographic data, clinical characteristics of OA, including the "Questionario Semantico Reumatologico" (QSR) pain questionnaire, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Lequesne indices, and information on previous diagnostic and therapeutic interventions was administered. RESULTS: A total of 4,109 patients were enrolled. Of them, 2356 were affected by knee OA and 1817 by hip OA. There were 2863 (69.7%) women and 1246 (30.3%) men. Median age was 68.2 years (range 50-103 years). Of the 4109 enrolled subjects, 3128 (76.1%) reported one or more medical comorbidities, mostly cardiovascular (52.7%), endocrinological (14.7%), gastrointestinal (13.4%), and respiratory (11.2%) disorders. The median pain visual analogue scale (VAS) score was 58.1+/-22.6 mm, higher in women (60.2+/-22.3 mm) than in men (53.3+/-22.6mm) (p<0.00001). OA pain was also higher in patients from Southern Italy (p<0.00001). NSAIDs were administered to nearly 70% of patients, COX-2 inhibitors to 55%, disease-modifying anti OA drugs to 19% and analgesics to 28.2%. Differences in drugs utilization were associated with OA localization and patient's geographical origin. Results of the WOMAC index were similar throughout groups. Responses to the QSR pain questionnaire showed differences, which are related to OA localization and geographical origin of the patients. CONCLUSIONS: The MI.D.A. study can help to better understand the patterns of pain in osteoarthritis and the associated treatment.

Down-modulation of chemokine receptor cartilage expression in inflammatory arthritis.

OBJECTIVE: To evaluate in vivo expression of chemokine receptors in cartilage tissue samples from healthy and diseased joints. METHODS: Presence and distribution of several chemokine receptors in cartilage samples from patients with osteoarthritis (OA) or inflammatory arthritis (IA) and from multi-organ donors were assessed by immunohistochemistry. The expression of messenger RNA (mRNA) for chemokine receptors was also analysed by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Normal and OA-affected cartilage showed a moderate to high expression of chemokine receptors, while staining of IA samples ranged from low to absent. Differences between OA and IA samples were present for all receptors but CCR2 and CXCR4. Moreover, mRNAs for CCR1, CCR5 and CXCR1 were found both in normal and pathological chondrocytes, suggesting that chemokine receptor down-modulation seen in IA samples could be a post-transcriptional event. CONCLUSION: Data on normal and pathological chondrocytes underline the role of chemokines in cartilage homeostasis and suggest an imbalance towards catabolic processes in inflammatory conditions.

[Long term study on the efficacy and safety of lornoxicam in rheumatoid arthritis]. / Studio a lungo termine su efficacia e sicurezza terapeutica di lornoxicam nell'artrite reumatoide.

BACKGROUND: To assess the long term safety and therapeutic action of lornoxicam, a new non steroidal anti-inflammatory agent, in rheumatoid arthritis. METHODS: Open trial was carried out on different dosage schedules of lornoxicam (4 or 8 mg bid and 4mg tid) administered for six to twelve months. Patients of both sexes were enrolled, with classical or definite rheumatoid arthritis according to the A.R.A. criteria. RESULTS: Thirty-four patients (28 F, 6 M) were admitted, mean age (+/- SD) 53.9+/-14.2 years, mean duration of illness 9.2+/-10.7 years. Lornoxicam 8-16 mg/day showed good safety and therapeutic activity in long term treatment. Clinical improvement was limited, but progression of the disease was controlled. No adverse events were complained. CONCLUSIONS: Lornoxicam presented a worth-while therapeutic action and a good tolerability in rheumatoid arthritis long term treatment.

Morphological analysis of articular cartilage biopsies from a randomized, clinical study comparing the effects of 500-730 kDa sodium hyaluronate (Hyalgan) and methylprednisolone acetate on primary osteoarthritis of the knee.

OBJECTIVE: Histomorphometric study on cartilage samples taken from osteoarthritic human knees before and 6 months after intraarticular injections of a specific fraction (500-730 kDa) of hyaluronan. The results obtained with hyaluronan were compared with the results of methylprednisolone acetate treatment. METHODS: Twenty-four subjects with primary osteoarthritis (OA) of the knee were considered. Eleven patients were treated with Hyaluronan (Hyalgan), 20 mg/2 ml once a week for 5 weeks) and 13 with methylprednisolone (Depo-Medrol, 40 mg/1 ml once a week for 3 weeks). At the time of baseline and after 6 months from the start of treatment, biopsies of cartilage were taken and processed for electron microscopy. Articular surface morphology, territorial matrix, chondrocyte number and ultrastructure were characterized by a set of morphometric parameters. Samples from 19 informed patients showing no arthroscopic sign of OA were also used for comparison. RESULTS: Six months after hyaluronan treatment a significant reconstitution of the superficial layer were observed together with an improvement in chondrocyte density and territorial matrix appearance. Furthermore, chondrocytes appeared significantly improved in their metabolism, as indicated by the increased extension of the synthetic structures and mitochondria with respect to the organelles having catabolic or storage functions. Hyaluronan treatment produced results that were significantly superior to those delivered with Methylprednisolone in almost all the morphometric estimators. CONCLUSIONS: These results cannot be explained simply by temporary restoration of the synovial fluid viscoelasticity, and provide further evidence that the specific fraction of hyaluronan used in this study is a useful tool in OA treatment, with a potential structure-modifying activity.

High in vivo expression of interleukin-17 receptor in synovial endothelial cells and chondrocytes from arthritis patients.

OBJECTIVE: To evaluate the presence of interleukin-17 (IL-17) and the expression of IL-17 receptor (IL-17R) in joint tissues from subjects with different arthritides. METHODS: Immunohistochemistry was used on frozen synovial and cartilage biopsies to identify cells expressing IL-17 and IL-17R. RESULTS: IL-17 staining was present only in synovial biopsies of rheumatoid arthritis (RA) (seven out of nine cases). IL-17R was expressed by all synovial biopsies evaluated except for three cases of post-traumatic arthritis (PTA). Vascular endothelial cells mainly expressed IL-17R. The percentage of IL-17R(+) vessels was the highest in RA synovium and the lowest in PTA. Chondrocytes from all types of arthritides were negative for IL-17 staining, but expressed IL-17R; the highest percentage of positive chondrocytes was found in seronegative spondylarthritis and the lowest in RA. CONCLUSIONS: IL-17-positive cells are found exclusively in RA. On the other hand, synovial endothelial cells and chondrocytes expressing IL-17R are found in the majority of patients with different types of arthritis. This finding suggests a role for a second ligand for IL-17R, which could be either a different cytokine or a different isoform of IL-17.

Morphological analysis of knee synovial membrane biopsies from a randomized controlled clinical study comparing the effects of sodium hyaluronate (Hyalgan) and methylprednisolone acetate (Depomedrol) in osteoarthritis.

OBJECTIVE: The study was part of a randomized open-label clinical trial designed to evaluate the effects of intra-articular injections of hyaluronan (Hyalgan) (HY) in osteoarthritis (OA) of the human knee. Data were compared with those obtained after treatment with methylprednisolone acetate (Depomedrol) (MP). METHODS: Synovial membranes from patients with OA of the knee, primary or secondary to a traumatic event and classified according to the American College of Rheumatology criteria, were examined by arthroscopy and by light and electron microscopy before and 6 months after local injection of HY (2 ml of 500-730 000 MW hyaluronan, 10 mg/ml in saline, one injection per week for 5 weeks) or MP (1 ml of methylprednisolone acetate, 40 mg/ml, one injection per week for 3 weeks). RESULTS: Arthroscopy revealed a significant decrease in inflammatory score after both treatments. Histology showed that HY treatment was effective (P< or =0.05) in reducing the number and aggregation of lining synoviocytes, as well as the number and calibre of the vessels. MP treatment significantly reduced the number of mast cells in primary OA. Both treatments tended to decrease the number of hypertrophic and to increase the number of fibroblast-like lining cells, to decrease the numbers of macrophages, lymphocytes, mast cells and adipocytes, and to decrease oedema, especially in primary OA, and to increase the number of fibroblasts and the amount of collagen. These phenomena were evident throughout the thickness of the synovial tissue. CONCLUSION: At least in the medium term, both HY and MP modified a number of structural variables of the synovial membrane of the osteoarthritic human knee towards the appearance of that of normal synovium. The effect was more evident in primary OA than in OA secondary to a traumatic event. This is the first evidence that local hyaluronan injections modify the structural organization of the human knee synovium in OA.

[Relapsing polycondritis associated with microscopic polyangiitis: description of a clinical case] / Policondrite ricorrente associata a poliangioite microscopica: descrizione di un caso clinico.

A clinical case of Relapsing Polychondritis (RP) with Microscopic Polyangiitis (MPA) is described in a 66 years old woman. This case represents a rare association of the two pathologies. Polychondritis is a rare inflammatory disease of unknown origin, but immunological mechanisms are essential in the pathogenesis. Histological features are inflammation and destruction of cartilage. The disease is systemic, may have a remitting course. The osteoarticular lesions are sometimes unusual, involving the temporomandibular or cervical articulations, and the renal lesions may be severe. This can be primary or associated with several other diseases. Microscopic Polyangiitis is a systemic disorder characterized by necrotizing vasculitis, affecting the small vessels. Most patient with MPA have Antineutrophil Cytoplasmic Antibodies for Myeloperoxidase (MPO-ANCA). ANCA have become an established tool for the diagnosis of systemic vasculitis. The primary target antigens for ANCA are myeloperoxidase (enzyme present in the secretory granules of neutrophils and monocytes) and antibodies to these antigens are tested by ELISA and IIF (indirect immunofluorescence). We describe a case of histologically confirmed MPA with Relapsing Polychondritis. Clinically she presented livedo reticularis in the lower limbs and pain in the joints. During the follow-up the patient developed asymmetric oligoarticular arthritis. Immunosuppressive drugs like glucocorticoids and cyclofosfamide are the drugs of choice, depending on the stage and severity of the disease.

Vascular endothelial growth factor production in polymyalgia rheumatica.

OBJECTIVE: To evaluate peripheral production and synovial expression of vascular endothelial growth factor (VEGF) in polymyalgia rheumatica (PMR). METHODS: Circulating levels of VEGF in PMR (serum concentration and in vitro release by peripheral blood mononuclear cells [PBMC]) were investigated by enzyme-linked immunosorbent assay. Local expression of VEGF in shoulder synovial tissue was investigated by immunohistochemical analysis. Investigations were performed in patients with active, untreated disease and in patients treated with corticosteroids. RESULTS: VEGF serum concentrations were significantly higher in untreated PMR patients than in normal control subjects. During steroid treatment, VEGF serum concentrations reached their lowest level after the sixth month of treatment. PBMC isolated from untreated PMR patients spontaneously secreted a higher amount of VEGF compared with PBMC from control subjects. Corticosteroid therapy did not affect the ability of PBMC to produce VEGF. Immunohistochemical staining performed on shoulder synovial tissue showed VEGF expression in both the lining layer and the sublining area. In 3 of 4 treated patients, no VEGF staining was found in synovial tissue during corticosteroid therapy. VEGF expression correlated with vessel density, but was not associated with alphavbeta3 and alphavbeta5 integrin expression. CONCLUSION: Peripheral and local VEGF releases have different responses to steroid treatment in PMR. The lack of response to corticosteroids by peripheral VEGF production supports the hypothesis that systemic involvement is dominant in PMR. At the synovial level, VEGF production is linked to vascular proliferation and is thus directly involved in the pathogenesis of synovitis.

Enhanced and coordinated in vivo expression of inflammatory cytokines and nitric oxide synthase by chondrocytes from patients with osteoarthritis.

OBJECTIVE: To evaluate the sites of expression of interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNFalpha), and inducible nitric oxide synthase (iNOS) in patients with inflammatory and degenerative joint diseases. METHODS: Cytokines and iNOS were detected by immunohistochemistry analysis of synovial and cartilage biopsy specimens obtained at knee arthroscopy in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), osteoarthritis (OA), and traumatic knee arthritis. Cytokine and iNOS expression was quantified using computerized image analysis. RESULTS: IL-1beta, TNFalpha, and iNOS were highly expressed by synovial cells (lining layer cells, infiltrating leukocytes, endothelial cells) from patients with inflammatory arthritides and significantly less by synovial cells from patients with OA and traumatic arthritis. In contrast, the latter patients showed high chondrocyte expression of cytokines and iNOS while RA and PsA patients had only minor chondrocyte positivity. In both joint compartments, IL-1beta expression, TNFalpha expression, and iNOS expression were strongly correlated. CONCLUSION: The enhanced and coordinated expression of IL-1beta, TNFalpha, and iNOS by chondrocytes strongly supports the hypothesis that chondrocytes are the major site of production of mediators of inflammation in human OA, thus playing a primary role in the pathogenesis of this disease.

Intra-articular hyaluronic acid in the treatment of osteoarthritis of the knee: clinical and morphological study.

OBJECTIVE: To evaluate, in a pilot, open clinical trial on 40 patients with knee osteoarthritis, the structural changes in the synovial membrane and cartilage following treatment with intra-articular hyaluronic acid (HA-Hyalgan). METHODS: The structural effects of HA given as 5 weekly injections (20 mg/2 ml once a week for 5 weeks), were evaluated by microarthroscopy and morphological analysis of biopsy samples taken at baseline and after 6 months, under blind conditions. Clinical efficacy was also evaluated using visual analogue scales for pain and functional parameters. RESULTS: At 6 months, the microarthroscopic evaluation indicated that the majority of the patients (60%) showed no changes compared to baseline, while 32.5% of the patients showed improvement in the grading and/or extension of cartilage lesions and 7.5% showed a worsened condition. These changes were accompanied by a statistically significant reduction in the synovial inflammation (p = 0.001). The results were confirmed by morphological examination of the cartilage and synovial membrane. At 6 months compared to baseline, a statistically significant reconstitution of the superficial amorphous layer of the cartilage (p = 0.0039), an improvement in the chondrocyte density (p = 0.0023) and vitality (p = 0.05), and a statistically significant reduction in synovial inflammation (p = 0.0001) accompanied by a significant increase in the synovial repair process (p = 0.0001) were observed. Significant and long lasting improvement in pain and joint mobility were also seen after HA treatment. Joint effusion, when present, was reduced. The treatment was well tolerated. CONCLUSION: Hyalgan represents a useful therapy for knee OA, with long-lasting symptomatic efficacy and potential positive effects on joint tissues. Other studies, in particular placebo-controlled studies, are warranted to confirm these promising results observed on joint tissues.

Inter-observer reliability of the arthroscopic quantification of chondropathy of the knee.

BACKGROUND: Several scoring systems have been proposed in order to quantify the degree of cartilage damage observed by arthroscopy of the knee in patients with osteoarthritis. OBJECTIVE: To evaluate the inter-observer reliability of five different scoring systems of arthroscopic evaluation for chondropathy in osteoarthritis of the knee and to evaluate the utility of a training session between different observations on these scoring systems. METHODS: Videotapes of knee arthroscopies on five patients with osteoarthritis demonstrating different levels of severity of cartilage damage of the medial tibiofemoral compartment were analyzed by nine observers prior to (pre-training evaluation) and 2 months after a 6 h training session (post-training evaluation) by the following scoring systems: (1) cartilage deterioration by a 100 mm visual analogue scale (VAS), (2) overall assessment of degeneration in the entire medial compartment (cartilage, meniscus, osteophyte) using a 100 mm VAS, (3) French Society of Arthroscopy (SFA) Scoring System, (4) SFA Grading System, (5) American College of Rheumatology (ACR) Scoring System. RESULTS: At the pre-training evaluation, the SFA grading system produced the highest coefficient of reliability (r = 0.94), the other systems recording levels of < or = 0.80. At the post-training evaluation, the coefficient of reliability was r > 0.80 for four of the five scoring systems, with lack of improvement in the ACR Scoring System. CONCLUSION: There was an improved and acceptable inter-observer reliability for at least 2 months follow-up in four of five evaluated scoring systems of arthroscopically graded osteoarthritis of the knee following a training session. A scoring system using a 100 mm VAS may produce the best inter-observer reliability. These results show that scoring chondropathy is possible and demonstrate the importance of training in the analysis of articular cartilage breakdown.

Synovial expression of cell adhesion molecules in polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is a common disorder of the elderly: the pathogenesis of the syndrome is still debated, though active synovitis of the shoulder has recently been confirmed. To investigate the pathogenesis of this synovitis we evaluated cell adhesion molecule (CAM) expression in shoulder synovial tissue from patients with PMR, correlated synovial expression with the serum levels of soluble forms, and assessed the changes associated with corticosteroid treatment. Arthroscopic synovial biopsies were obtained from 12 untreated and seven corticosteroid (CS)-treated cases. CAM expression was evaluated by MoAb staining on frozen sections and computerized image analysis. Soluble CAM were quantified by ELISA. Endothelial cells expressed intercellular adhesion molecule-1 (ICAM-1), E- and P-selectins. Infiltrating cells were ICAM-1 and beta1-integrin-positive, while L-selectin expression was limited to intravascular leucocytes. Synovial lining cells strongly expressed vascular cell adhesion molecule-1 (VCAM-1), and less intensely ICAM-1. Only the soluble form of ICAM-1 (sICAM-1) was elevated in untreated patients. CS treatment was associated with a decrease in ICAM-1, VCAM-1 and E- and P-selectin expression. sICAM-1 levels were in the normal range in treated patients. VLA-5 and 6 expression was widely distributed among cell types, and was not CS-sensitive. Active shoulder synovitis is associated with different CAM expression in PMR. ICAM-1 expression is widely distributed and correlates with elevated levels of the soluble form; it is significantly lower in CS-treated asymptomatic cases.

Prevention with sucralfate gel of NSAID-induced gastroduodenal damage in arthritic patients.

OBJECTIVES: To evaluate the efficacy of a new formulation of sucralfate as gel (Gastrogel) in the short-term prevention of gastroduodenal lesions in arthritic patients receiving nonsteroidal anti-inflammatory drugs. METHODS: One hundred seven patients with arthritis (M/F 18/89, mean age 55.2 +/- 9.7 yr) enrolled in two centers were considered eligible for the study if initial endoscopy showed the absence of any relevant mucosal damage. Patients were randomly allocated to receive diclofenac 200 mg/day or naproxen 1 g/day plus either sucralfate gel 1 g b.i.d. (N = 53) or identical placebo (N = 54) for 14 days in a randomized double-blind study. Repeated assessment of GI symptoms and endoscopy were performed at the end of the study period. RESULTS: At final endoscopy the incidence of erosion and the mean endoscopic score for both stomach and duodenum were significantly lower in the sucralfate gel group compared with placebo group (p < 0.05). Both heartburn and epigastric pain were significantly less frequent in patients receiving sucralfate gel than placebo (51 vs 30% and 49 vs 28% for heartburn and epigastric pain, respectively, p < 0.05). No differences were observed in the incidence or in the mean score for nausea. An unexplained difference in the incidence of ulcers was found between the two centers, but in both a similar reduction in the incidence of ulcers was observed between patients receiving sucralfate gel compared with those receiving placebo. The overall difference (8% in sucralfate-treated patients, 28% in patients receiving placebo) of gastroduodenal ulcers was statistically significant (p < 0.05). CONCLUSIONS: Sucralfate gel reduces both the incidence of acute gastroduodenal mucosal lesions and symptoms in patients with arthritis receiving short-term nonsteroidal anti-inflammatory drugs.