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About 40% of nonfunctioning pancreatic endocrine carcinomas (NF-PEC) cannot be cured by surgery due to advanced stage disease. Somatostatin analogues have been proposed as first line therapy in these cases. We performed a prospective phase IV study to assess the efficacy of octreotide in advanced NF-PEC and identify factors predictive of response to therapy. Twenty-one consecutive patients with octreoscan-positive advanced-stage well-differentiated NF-PEC were treated with long-acting release octreotide 20 mg i.m. at diagnosis. The immunohistochemical expression of somatostatin receptor 2 (SSTR2) and the quantitative mRNA analysis of SSTR2 and SSTR5 were assessed in 12 tumours. The tumour proliferative fraction was assessed by immunohistochemistry for Ki-67. Eight patients (38%) had stable disease (SD) after a median follow-up of 49.5 months. Thirteen patients (62%) developed progression after a median of 18 months. Tumour progression correlated with a proliferative index ≥5% (P=0.016), weight loss (P=0.006) and absence of abdominal pain (P=0.003) at diagnosis. Other clinical (age, gender and primary tumour resection) or pathological parameters (site, size and liver metastasis) lacked significant correlation with tumour progression. No difference in the amount of SSTR2 mRNA and protein or SSTR5 mRNA was found between tumours that were stable (n=5) and seven tumours that progressed (n=7). Treatment with long-acting release octreotide was associated with stabilization of disease and a good quality of life in 38% of patients. A Ki-67 index ≥5% and/or the presence of weight loss may justify more aggressive therapy without waiting for radiologically proven progression of disease.

OBJECTIVE: To examine consecutive patients with Whipple's disease (WD) for the full clinical spectrum of spondyloarthritis. METHODS: Nine consecutive patients, 8 men, 1 woman, with WD were clinically evaluated and examined for clinical and radiological manifestations of spondyloarthritis by 2 rheumatologists with special interest in spondyloarthritis. The mean age of the patients at the time of study and at the time of their initial diagnosis of WD by duodenal biopsy was 62.4 years (range 42-71) and 54.4 years (range 40-62), respectively. Each patient had an anteroposterior radiographic view of the pelvis and also had HLA typing for class I and II alleles. Pelvis radiographs were read blindly for evidence of sacroiliitis. RESULTS: All but one patient had rheumatologic manifestations related to WD. The mean interval between the onset of these symptoms and the diagnosis of WD was 6.1 years (range 1-15). One had recurrent polyarthritis, 1 recurrent oligoarthritis, 3 recurrent monoarthritis, 2 recurrent synovitis with pitting edema of the dorsum of hands and/or feet, and 1 isolated De Quervain's tenosynovitis. Of the 5 patients with arthritis, 3 also had episodes of swelling with pitting edema over the dorsum of hands and/or feet together with flexor digit tenosynovitis, 2 also had olecranon bursitis, and 1 tibial tenosynovitis. No patient had clinical or radiological manifestations of spondyloarthritis. None had the HLA-B27. CONCLUSION: In Italian Caucasian patients with WD there was no association with spondyloarthritis and HLA-B27.

Summary Fifty-two patients with psoriatic arthritis (PA), treated with auranofin (AF), were entered into a one year prospective, open study. The total group showed a significant increase in frequency of HLA antigens A1 and B38, and a reduction of B5 when compared to healthy controls. There was a remission or an important improvement of disease in the 51 % of 45 patients who completed the study. The rate of withdrawal due to side effects was low (8.8%) and the toxicity was mild in nature (diarrhoea and mucocutaneous rash). We prospectively sought predictors of response using HLA antigens, and clinical and laboratory parameters at the beginning of therapy. The only 3 factors found to be related to outcome were duration of psoriasis, physician and patient assessment of disease activity. No laboratory data or HLA specificities could be associated with substantial response to AF therapy.

The aim of the study was to evaluate the relationship between the presence of the 'rheumatoid epitope' defined by a sequence motif in the HLA-DRB1 alleles, rheumatoid factor and disease severity in Northern Italian patients with rheumatoid arthritis (RA). Twenty-nine DR4-positive and 47 DR4-negative RA patients were studied. Each DR4-positive patient was matched with two DR4-negative controls of similar disease duration and sex. HLA-DRB1 alleles were determined in the 86 patients and 351 controls from the same geographical area. The patients were retrospectively evaluated for extra-articular features (EAF) and radiographic damage. The rheumatoid epitope was expressed in 45% of patients. No significant differences in the presence of rheumatoid factor, EAF and articular damage were observed between patients with no, one or two doses of epitope. However, the patients encoding the epitope by an HLA-DR4 allele had a higher number of eroded joints and a higher Larsen score compared to those without the epitope. No differences were present between patients expressing HLA-DRB1*-01 alleles and those lacking the rheumatoid epitope. Even in the absence of expression of the rheumatoid epitope, seropositive patients had more EAF and more erosive disease compared to those who were seronegative. Even if most Northern Italian RA patients do not express the rheumatoid epitope, the radiological severity of disease is associated with HLA-DRB1*04 alleles.Key words: Rheumatoid arthritis, Severity, HLA-DRB1 alleles, Rheumatoid factor.

The aim of the study was to evaluate the relationship between the presence of the 'rheumatoid epitope' defined by a sequence motif in the HLA-DRB1 alleles, rheumatoid factor and disease severity in Northern Italian patients with rheumatoid arthritis (RA). Twenty-nine DR4-positive and 47 DR4-negative RA patients were studied. Each DR4-positive patient was matched with two DR4-negative controls of similar disease duration and sex. HLA-DRB1 alleles were determined in the 86 patients and 351 controls from the same geographical area. The patients were retrospectively evaluated for extra-articular features (EAF) and radiographic damage. The rheumatoid epitope was expressed in 45% of patients. No significant differences in the presence of rheumatoid factor, EAF and articular damage were observed between patients with no, one or two doses of epitope. However, the patients encoding the epitope by an HLA-DR4 allele had a higher number of eroded joints and a higher Larsen score compared to those without the epitope. No differences were present between patients expressing HLA-DRB1*-01 alleles and those lacking the rheumatoid epitope. Even in the absence of expression of the rheumatoid epitope, seropositive patients had more EAF and more erosive disease compared to those who were seronegative. Even if most Northern Italian RA patients do not express the rheumatoid epitope, the radiological severity of disease is associated with HLA-DRB1*04 alleles.

<it>Objective</it>. Oxidative stress may be one of the important complex pathogenetic mechanisms that lead to damage in scleroderma; free radicals may provoke endothelial injury, fibroblast proliferation and fragmentation of autoantigens favouring induction of autoantibodies. The present study investigates the oxidant status in scleroderma patients by measuring the urinary concentration of 8-isoprostaglandin-F<inf>2α</inf>, an F<inf>2</inf>-isoprostane, and a product of free radical-mediated peroxidation of arachidonic acid. <it>Methods</it>. Forty-three scleroderma patients (42 women and 1 man, mean age 54.1 yr, mean disease duration 9.0 yr) underwent clinical evaluation and instrumental investigations in order to assess skin, vascular, lung and heart involvement. Von Willebrand factor was evaluated as marker of vascular dysfunction in 36 out of the 43 cases. The urinary level of 8-isoprostaglandin-F<inf>2α</inf> was measured in all scleroderma patients and in the 43 age- and sex-matched healthy controls. <it>Results</it>. Urinary levels of 8-isoprostaglandin-F<inf>2α</inf> were higher in scleroderma patients than in the healthy control group (341.7 <it>vs</it> 147.6 pg/mg creatinine; <it>P</it><0.001). Values of 8-isoprostaglandin-F<inf>2α</inf> were strongly correlated with the nailfold videocapillaroscopy pattern and lung involvement (<it>P</it>=0.002 and 0.003, respectively), showing increasing levels with the progression of pulmonary severity. Correlation between 8-isoprostaglandin-F<inf>2α</inf> level and von Willebrand factor narrowly failed to reach statistical significance (<it>P</it>=0.05). There was no correlation between 8-isoprostaglandin-F<inf>2α</inf> concentration and disease activity, vascular, skin and heart involvement, disease pattern or autoantibody profile. <it>Conclusions</it>. Our study further supports the role of oxidant stress in the pathogenesis of scleroderma, showing a strong correlation between a marker of free radical damage with both the severity of lung involvement and the videocapillaroscopic patterns.