Synovitis in polymyalgia rheumatica: an immunogenetic study.
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Publications and source records attributed to C Salvarani.
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The radiological changes of the cervical spine were evaluated in 57 patients with psoriatic arthritis and were correlated with clinical, radiological, and immunogenetic features of the disease. Forty patients (70%) showed radiological evidence of the cervical spine being affected by the disease. Two patterns of cervical spine abnormalities were noted. Fifteen patients (26%) had erosive and/or subluxing cervical rheumatoid like lesions; 25 patients (44%) had a more frequently reported pattern similar to ankylosing spondylitis. Although subaxial subluxations were the most frequently observed cervical abnormalities (53%) in the inflammatory subgroup, none of the patients studied had cord compression. Ankylosing cervical spine disease was the only form of axial involvement in nine (36%) of 25 patients with the ankylosing form of psoriatic arthritis. All of these patients had peripheral disease and were B27 negative. Predictors of cervical spine disease patterns were considered using clinical, demographic, and radiological features and HLA antigens. The results of a multivariate analysis showed that the best predictors of inflammatory cervical spine disease are the presence of HLA-B39 and HLA-DR4 antigens, radiocarpal erosions, and the absence of the HLA-DR5 antigen.
Twelve patients with psoriatic arthritis (PsA) and very active articular disease resistant to conventional second line therapy entered into a 6-month open study of cyclosporine A (CsA) at a starting dosage of 3 mg/kg/day. Comparisons of phenotypic characteristics of lymphocytes and response to mitogens of peripheral blood mononuclear cells (PBMC) were made between these patients with PsA before CsA therapy, 7 patients without prior 2nd line therapy, 14 untreated patients with psoriasis alone, and 61 healthy controls. We confirmed a significant reduction of the basal percentage of CD8+ cells and an increase in the CD4/CD8 ratio in patients with PsA before CsA therapy compared to controls. These abnormalities were not present in patients with PsA without prior 2nd line therapy and in patients with psoriasis alone. Peripheral blood activated T cells (CD3+, HLA-DR+), natural killer (NK) (CD3-, CD16+ and/or CD56+), total B and CD5+ B cells were decreased only in patients with PsA before CsA therapy. The reduction of non-MHC restricted cytotoxicity T (CD3+, CD16+ and/or CD56+) was observed in all the 3 groups of patients compared to controls. After the 6 months of CsA therapy we observed a significant increase of CD3+, HLA-DR+, CD3+, CD16+ and/or CD56+, total B, and CD20+, CD5+ cells in the 11 patients with PsA compared to pretreatment values. Contrary to azathioprine, CsA does not impair the NK cell population which has a protective role against cancer and viral infections.
Luteal function, endometrial receptivity, endometrial prolactin and glycoprotein secretions, blastocyst-secreted immunomodulant factors and embryo quality are nowadays considered the main determinants involved in embryo implantation control. The endometrial factors are progesterone-dependent. Out of 128 cycles of ART (AIH-IU, GIFT, IVF-ET), performed in 67 women at the Dept. of Obstetrics and Gynaecology of Parma during the period 1986-1991, 31 conceptions were obtained (pregnancy rate: 24.21%), 7 of which miscarried (abortion rate: 22.58%). According to these data, ART high abortion rate is possibly connected with poor luteo-endometrial function and poor embryo quality. Controlled ovarian hyperstimulation is thought to inhibit embryo implantation after IVF-ET by decreasing endometrial receptivity. Such a situation can be treated either by exogenous progesterone administration or by tubal techniques (GIFT, TET) performed in non-tubal infertility. Both strategies showed to better endometrial receptivity. A delayed intrauterine embryo transfer at blastocyst stage, when cocultures allow to, is supposed to raise the implantation rate in tubal infertility by enhancing embryo selection and endometrial receptivity. This paper also reports preliminarily on the predictive value of beta-HGC and estradiol levels, as well as of endometrial thickness, on early pregnancy outcome.
Serum levels of soluble interleukin 2 receptors (sIL-2R) were measured in 21 patients with polymyalgia rheumatica (PMR)/giant cell arteritis (GCA) prior to steroid treatment. These levels were significantly elevated in patients with PMR/GCA compared with healthy controls (p = 0.002). A significantly longer duration of morning stiffness (p = 0.005) was observed in patients with a high concentration of sIL-2R. A significant correlation was observed at diagnosis between sIL-2R and erythrocyte sedimentation rate (ESR) (p = 0.01) and between ESR and C-reactive protein (CRP) (p = 0.005). We investigated prospectively a group of 10 patients over a period of 6 months of prednisone therapy. At the end of the study sIL-2R levels fell significantly compared to pretreatment values (p = 0.02), but remained significantly higher compared to controls (p = 0.02). ESR and CRP values also fell significantly compared to pretreatment levels (p = 0.0001 in both cases). We observed a significant correlation between the decrease in ESR values and the decrease in sIL-2R and CRP levels after 6 weeks (p = 0.01 in both cases) and after 6 months of therapy (p = 0.002 and p = 0.05). sIL-2R may be considered a useful serologic marker for monitoring response to steroid therapy in patients with PMR/GCA. This laboratory variable correlated more closely with ESR than with CRP. The presence of elevated levels of sIL-2R is likely to reflect T cell activation occurring in PMR/GCA. T lymphocyte activation persisted after 6 months of steroid therapy, despite rapid and continuous control of disease manifestations.
Twelve patients with psoriatic arthritis (PsA) were treated with low doses of cyclosporine A (CsA) (the initial dose was 3 mg/kg daily) and were entered into an open 6-month study. At the end of the study arthritis was improved in 7 patients (number of patients achieving a 50% or more reduction in the number of swollen or tender joints) and unchanged in 4 patients. Cutaneous psoriasis also improved significantly as shown by psoriasis area and severity index score. Only one patient withdrew from the study after one month because of severe nephrotoxicity. Serum creatinine fell to baseline value 6 weeks after the discontinuation of CsA. Three patients had minor side effects. CsA maintained articular improvement also in the 9 patients who are still taking this drug (mean duration of therapy of 12 +/- 0.8 months). There was no significant reduction of erythrocyte sedimentation rate during the study period. We assayed levels of soluble interleukin 2 receptors (sIL-2R) in serial serum samples obtained from 10 patients during the study period. Concentrations of sIL-2R were significantly increased in patients with PsA compared to controls. In 6 responder patients we observed a parallel decrease in joint pain/tenderness score and serum sIL-2R values. This finding was not observed in 4 nonresponders. Our results suggest that low dose CsA is a short term effective and safe therapy in patients with PsA and that serial sIL-2R levels are a useful means of measuring changes in disease activity.
We performed retrospective analysis of 141 Northern Italian patients with rheumatoid arthritis (RA). This series represents all the patients seen as in and/or outpatients at the rheumatologic unit of Reggio Emilia Hospital during a 2 year period (1987-88). We observed a low frequency of nodules (16%) and vasculitis (2.1%). Thus, RA seems to be milder in our population compared to Caucasian patients with RA originating from North America or England. We observed a weak association with DR4 (RR = 2.4) in the total group of patients with RA. A low frequency of DR4 was observed in patients and controls (29 vs 14.5%, p = 0.001). When compared with controls the frequency of DR4 was significantly higher in seropositive (p = 0.001), but not in seronegative patients. We found that DR4 was significantly associated with nodules (RR = 6.4), with extraarticular features (EAF) (RR = 4) and with erosions (RR = 3) compared with controls. The subgroups with nodules and EAF had a DR4 frequency (respectively, of 52 and 40%) which was significantly higher than that observed in remaining patients (respectively, 25 and 24%). No significant difference was observed in the DR4 frequency between the patients with erosions and those without (34 vs 18%). Thus, DR4 in our population seems to be predominantly associated with a subgroup of patients characterized by seropositivity and EAF.
We studied the epidemiology of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) in a Mediterranean population. Ninety-nine patients with PMR and/or GCA were identified over a 9-year period (1980-1988) in Reggio Emilia, Italy. The average annual incidence of PMR and GCA was 12.7/100,000 and 6.9/100,000, respectively, in a population aged 50 years or older. Frequencies of HLA antigens were determined in 49 patients with PMR and/or GCA who were followed by staff at our rheumatology unit during the 1980-1988 period. When compared with HLA findings in 242 healthy controls, DR4 was not found to be significantly associated with PMR (24% in PMR patients versus 14% in controls). Patients with GCA also showed an increased frequency of DR4 compared with controls (36% versus 14%), but this difference was also not statistically significant. The immunogenetic features of PMR and GCA and the relationship between the immunogenetic and epidemiologic patterns in different populations are discussed.
Oxytocin (OT) administration has been shown to inhibit adrenocorticotropic hormone (ACTH)/cortisol secretion in several experimental conditions. In the present study, the plasma OT responses to suckling in 7 lactating women or to mechanical breast stimulation in 6 normally menstruating women (experimental tests) or to sham stimuli in the same subjects (control tests) were measured and correlated with the simultaneous changes in plasma ACTH/cortisol levels. All women showed similar basal levels of OT, ACTH and cortisol, which remained unmodified after sham stimulation. In contrast, both suckling and breast stimulation produced a significant increase in plasma OT levels and a significant decrease in plasma ACTH concentrations. When OT and ACTH data were considered together, a significant negative correlation was found between the OT increase and the simultaneous ACTH decline. Plasma cortisol levels were lower during suckling or breast stimulation than in control conditions. These data show an inverse relationship between plasma OT and ACTH levels during suckling and breast stimulation in humans, suggesting an inhibitory influence of OT on ACTH/cortisol secretion in a physiological condition.
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We treated 5 patients with rheumatoid arthritis (RA) with anemia of chronic disease with recombinant human erythropoietin (rHuEPO) for 11 weeks. An increase in hematocrit (Hct) greater than 5 was seen in 4 patients after 4 weeks of therapy. The 5th patient had a significant rise in Hct when the dosage of rHuEPO was increased to 150 units/kg from the 4th to 7th week. The subcutaneous administration of rHuEPO dose, reduced by one third with respect to initial dose, maintained an effective Hct value in all the 5 patients during the last 4 weeks of therapy. There was no change in disease activity. In one patient Hct normalization completely resolved symptoms of angina pectoris and permitted hip replacement surgery in another. No side effects occurred during rHuEPO therapy. We conclude that HuEPO is an effective, safe and well tolerated therapy for RA patients with severe anemia of chronic disease.
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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.
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The patient, a 55-year-old man with neuro-Behçet, developed superior vena caval occlusion. Antibodies to cardiolipin were detected in high titres in his serum and a decreased fibrinolysis was also found. It is suggested that anticardiolipin antibodies, perhaps decreasing fibrinolysis, may play an important pathogenic role in some patients with Behçet's disease.
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