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Biomedical subjects

L Boiardi

Publications and source records attributed to L Boiardi.

At least 19 recordsLinked to original sources

Distal musculoskeletal manifestations in polymyalgia rheumatica: a prospective followup study.

OBJECTIVE: To determine the frequency and the characteristics of distal musculoskeletal manifestations in polymyalgia rheumatica (PMR). METHODS: Prospective followup study of 177 consecutive patients meeting clinical criteria for PMR, diagnosed over a 5-year period in 2 rheumatology secondary referral centers in Italy. RESULTS: Seventy-nine of the 177 patients (45%) had distal musculoskeletal manifestations. Peripheral arthritis occurred in 45 patients (25%), carpal tunnel syndrome in 24 (14%), distal extremity swelling with pitting edema in 21 (12%), and distal tenosynovitis in 5 (3%). These manifestations were usually associated with PMR proximal symptoms (69%); however, 31% of the episodes represented isolated relapse/recurrence at distal sites. Distal symptoms responded promptly to corticosteroids. No evidence of joint deformities, erosions, or development of rheumatoid arthritis was observed during the followup. The group of patients with peripheral arthritis included a higher proportion of females, had a longer duration of therapy, and had more relapses/ recurrences. Patients who had distal extremity swelling with pitting edema had a higher age at disease onset, a shorter duration of therapy, and lower initial and cumulative prednisone doses. CONCLUSION: Inflammatory involvement of distal articular and/or tenosynovial structures occurs in approximately half of the cases of PMR. Peripheral arthritis is associated with more severe disease, while distal extremity swelling with pitting edema appears to identify a more benign disease subset.

Aged

The relationship between serum-soluble interleukin-2 receptor and radiological evolution in psoriatic arthritis patients treated with cyclosporin-A.

Aims of the study to evaluate the radiologically detected progression of joint damage in patients with psoriatic arthritis (PA) treated with cyclosporin-A (CsA) and to look for clinical and/or immunological parameters that might predict outcome. Twenty-four out-patients suffering from active PA entered a 2-year open prospective study on low-dose CsA (starting dose 3 mg/kg/day). Fifteen patients completed the study. Plain radiographs of hands and feet at study entry and at the end of follow-up were compared for the number of eroded joints. Serum-soluble IL-2 receptor (sIL-2R) levels were available in 13/15 patients before CsA therapy, after 6 months and after 2 years. The mean number of eroded joints per patient increased significantly during the study period (P = 0.017). Nine patients had less than two new eroded joints (responders) while the remaining six patients had five or more new eroded joints (non-responders). Serum sIL-2R levels were in the normal range after 6 months and 2 years of CsA treatment in all the responder patients and were above the 95th percentile of the control population in the six non-responders. We did not find any other demographical, clinical, radiological or laboratory parameter predictive of outcome in conclusion. (1) CsA seems to be able to control the 2-year progression of the radiologically measured damage in peripheral joints in 60% of PA patients. (2) A normal serum sIL-2R level after 6 months of therapy seems to have a prognostic value for a good outcome in PA patients treated with CsA.

Administration, Oral

HLA-DRB1 alleles associated with rheumatoid arthritis in Northern Italy: correlation with disease severity.

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 57 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.

Aged

Psoriatic arthritis.

Recent population-based studies have examined the incidence, prevalence, and survival rates of patients with psoriatic arthritis (PsA). Although there are still no completely satisfactory diagnostic criteria for PsA, Moll and Wright's criteria--although not a true classification/diagnostic scheme--are the most used. The sensitivity of these criteria is low (61%), as are the sensitivities of the European Spondyloarthropathy Study Group and Amor classification criteria for the whole spectrum of spondyloarthropathy. In some patients, PsA can occur only with peripheral enthesitis, particularly Achilles tendinitis or dactylitis. These patients may represent a subset of PsA that is not defined by the Moll and Wright or European. Spondyloarthropathy Study Group criteria and is, therefore, poorly recognized as such. Recent studies have analyzed the expression of adhesion molecules, cytokines, and chemokines in the synovial fluid and synovial membrane of patients with PsA. The therapeutic approach to PsA must be multidisciplinary, involving dermatologists and rheumatologists. Currently the most widely used second-line drugs are methotrexate, sulfasalazine, and cyclosporine. Used in combination, these drugs will probably become a well-established therapy for PsA.

Arthritis, Psoriatic

Serum chemokines in patients with psoriatic arthritis treated with cyclosporin A.

OBJECTIVE: To evaluate the levels of serum chemokines in patients with psoriatic arthritis (PsA) before and during cyclosporin A (CyA) treatment. METHODS: Sixteen outpatients with active PsA were followed for 6 months during low dosage CyA treatment. Serum chemokines of the C-X-C and C-C groups were determined by ELISA at the baseline. Serum RANTES levels were measured at 2 month intervals for 6 months. Serum chemokine levels were related with clinical and laboratory disease activity variables. RESULTS: Serum interleukin 8 and macrophage inflammatory protein 1alpha levels were undetectable at baseline. Mean serum growth related gene product-alpha and monocyte chemoattractant protein 1 values were reduced and serum RANTES were elevated compared to controls. CyA treatment did not change serum RANTES levels. Patients with PsA with persistently normal serum RANTES levels (4 patients) had a more favorable clinical and laboratory response to CyA compared to patients with persistently high serum levels (6 patients). CONCLUSION: Serum RANTES levels are higher in patients with PsA than in a control population. CyA treatment does not change RANTES values. Patients with PsA with persistently normal RANTES levels have a better response to CyA treatment.

Adult

Therapy with cyclosporine in psoriatic arthritis.

OBJECTIVE: To evaluate the efficacy and toxicity of cyclosporin A (CsA) in the treatment of patients with psoriatic arthritis (PsA). METHODS: We reviewed the literature dealing with CsA treatment of PsA. RESULTS: In the 1980s, some studies evaluating CsA in severe cases of psoriasis documented an improvement in the associated arthritis. Subsequently, open prospective studies included patients with active peripheral arthritis. Using initial CsA dose of 3 to 6 mg/kg/day, improvement in the clinical parameters was noted. A controlled trial showed that CsA and methotrexate (MTX) are equally effective treatment for PsA. CsA and MTX combination was effective in PsA patients resistant to previous second-line therapy. No studies have evaluated the efficacy of CsA on axial disease and on the progression of radiological damage. The most important side effect was nephrotoxicity. However, of 170 CsA-treated patients in 16 studies, only 10 (6%) discontinued the drug because of renal side effects. CONCLUSIONS: CsA seems to be an effective and safe therapy for PsA. However, controlled studies on large number of patients are necessary.

Antirheumatic Agents

Effects of desferrioxamine therapy on chronic disease anemia associated with rheumatoid arthritis.

OBJECTIVE: To investigate the effects of desferrioxamine (DFO) infusion on chronic disease anemia (CDA) of rheumatoid arthritis (RA) by evaluating interleukin-6 (IL-6) and erythropoietin (EPO) production. PATIENTS AND METHODS: Five patients with RA and CDA (group I) were treated with DFO, 500 mg daily, through a continuous 10-h subcutaneous infusion 5 days a week for 4 weeks. One month after withdrawal, DFO was resumed in all five group I patients (group II) with an increase to 1 g daily following the previous treatment schedule. Clinical and laboratory parameters were evaluated weekly during the two study periods. Serum EPO was measured by radioimmunoassay. IL-6 was detected by the enzyme-linked immunoabsorbent assay method. RESULTS: No significant variations in hematological parameters, IL-6 or EPO levels were observed in group I patients. After 1 week of DFO 1 g daily, reticulocyte counts and EPO improved significantly. Hemoglobin and hematocrit rose significantly after 3 weeks of 1 g daily DFO therapy. Four weeks after DFO withdrawal, EPO, reticulocyte counts, hemoglobin and hematocrit returned to baseline levels. A significant improvement in the clinical parameters of disease activity was observed, particularly in group II patients. CONCLUSION: DFO improves CDA in RA patients. The beneficial effects on erythropoiesis seem to be related to improved EPO responsiveness to the anemia.

Anemia

Testicular function in hypercholesterolemic male patients during prolonged simvastatin treatment.

Simvastatin is a very effective hypocholesterolemic drug which, reducing cholesterol biosynthesis, can affect normal steroid hormone production. Testes require a continuous cholesterol supply for testosterone synthesis and this can be derived from low density lipoprotein receptor-mediated uptake or from de novo local synthesis. The aim of the study was to see if prolonged simvastatin treatment compromised endocrine testicular function both in basal conditions and after stimulation by human Chorionic Gonadotropin (hCG) (Profasi 5,000 Ul, i.m. at 8 a.m.). Free testosterone (FT) levels were determined at baseline and after 3, 6 and 12 months of simvastatin treatment (20 mg/day) in eight hypercholesterolemic patients. At the same time we performed a hCG stimulation test to evaluate testicular reserve. A significant reduction of FT, both basal and hCG-stimulated, was observed in the 6th and the 12th month of the study. However, FT levels remained in the normal range and no patient complained of gonadal function related symptoms. No significant change was observed in estradiol response to hCG test. Lastly, there was no variation in LH, FSH, progesterone, 17-OH-progesterone, androstenedione or dehydroepiandrosterone-sulphate levels. Our study concluded that the drug causes a mild decline in FT secretion without any clinical sign of testicular dysfunction.

Androgens

CD8 lymphocyte subsets in active polymyalgia rheumatica: comparison with elderly-onset and adult rheumatoid arthritis and influence of prednisone therapy.

The aim of this study was to evaluate CD8 lymphocyte subsets in active polymyalgia rheumatica (PMR), to determine whether low percentages of CD8+ cells could be used to differentiate PMR from elderly-onset (EORA) and adult rheumatoid arthritis (RA), and to investigate the effects of prednisone on CD8 lymphocyte subsets. A significant reduction of percentages and absolute numbers of CD8bright+ cells was observed in patients with active PMR. Both CD8bright+, CD57- and CD8bright+, CD57+ subsets were significantly reduced. Reduced percentages of CD8+ cells were observed in 55% of patients with active PMR/giant cell arteritis (GCA), in 23% with EORA and in 44% with adult RA. Prednisone therapy in PMR patients, after only 1 week, increased the lymphocyte count and the absolute numbers of lymphocyte subsets significantly. However, the percentages of CD8bright+ cells remained persistently low for the 2 yr study period in 80% of the patients with low pre-treatment levels. Our results demonstrate that CD8 cell percentage is a poor epidemiological discriminator for PMR diagnosis. Notwithstanding the rise in absolute numbers of CD8 cell subsets induced by prednisone, the persistently low percentages of CD8+ cells in a group of PMR patients indicate an abnormality connected with the disease.

Age of Onset

Role of peripheral CD8 lymphocytes and soluble IL-2 receptor in predicting the duration of corticosteroid treatment in polymyalgia rheumatica and giant cell arteritis.

OBJECTIVES: To determine if the presence of low percentages of CD8 positive cells or high levels of soluble interleukin-2 receptors (sIL-2R) define a subgroup of patients with more severe polymyalgia rheumatica and giant cell arteritis (PMR/GCA). METHODS: 38 PMR/GCA patients were followed up prospectively. Serum levels of sIL-2R and peripheral blood CD8 lymphocytes were measured before the start of corticosteroid treatment, after six months of treatment and at the last visit. Phenotypical analysis of lymphocyte subpopulations was performed with a two colour technique, and assay of sIL-2R was performed using an enzyme-linked immunosorbent kit. Forty four healthy people matched for age and gender comprised a healthy control group. RESULTS: The median duration of follow up was 28 months (range 7-65). Corticosteroid treatment lasted a median of 23.5 months (7-65). Eleven patients (29%) were in remission at the end of follow up; 45% of the patients had at least one relapse or recurrence. Compared with controls, patients with active disease had a significantly lower percentage of CD8 cells and significantly increased sIL-2R levels. Erythrocyte sedimentation rate, C reactive protein, and sIL-2R values were significantly less after six months of steroid treatment compared with before treatment. The percentage of CD8 cells remained significantly lower at six months and the end of follow up compared with controls, while sIL-2R levels remained significantly greater. Patients in whom the percentage of CD8 cells at six months was lower than one SD of the mean of normal controls (26%) had a significantly longer duration of corticosteroid treatment, a greater cumulative dose of prednisone and more relapses or recurrences compared with patients in whom the percentage was in the normal range. The duration of treatment and the cumulative dose of prednisone were not influenced by the percentage of CD8 cells before treatment therapy or by the levels of sIL-2R after six months of treatment. CONCLUSIONS: A reduced percentage of CD8 cells after six months of treatment may be a useful outcome parameter which would identify a group of PMR/GCA patients likely to experience more severe disease, defined as longer duration of corticosteroid treatment, higher cumulative dose of prednisone, and relapse or recurrence of disease.

Aged

Short and long-term effects of growth hormone treatment on lipid, lipoprotein, and apolipoprotein levels in short normal children.

Since recombinant growth hormone (GH) has been available, its use has been extended to treating not only children with growth hormone deficiency, but also short-statured children without GH deficiency. It is interesting, therefore, to determine whether GH therapy given in conventional doses causes metabolic side effects in these patients. In the present study we have examined the effect of recombinant human GH on eleven short normal children. Patients received 12 U/m2/week for 1 year. Before beginning treatment, the children had a mean annual growth velocity of 5.1 +/- 0.9 cm/yr; during the year of treatment, the therapy was effective and improved the mean growth velocity to 7.1 +/- 1.7 cm/yr, p < 0.05. We evaluated the subacute short-term effects during the first 15 days of treatment and the long-term effects for one year of GH treatment on lipid and lipoprotein levels. We found a significant increase in total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) at the 6th month. Triglycerides (TG) increased significantly at the 3rd and 6th month. Both TC and TG returned to baseline at the 12th month. In no case however did the levels of TC, LDL-C and TG go above normal nor were there any changes in the following tests: high density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) A-I, Apo B, Apo C-II, Apo C-III and Apo E. In conclusion, conventional doses of GH given to short normal children are effective in ameliorating growth velocity and do not cause serious metabolic side effects.

Adolescent

Elevated soluble intercellular adhesion molecule 1 in the serum of patients with polymyalgia rheumatica: influence of steroid treatment.

OBJECTIVE: To determine the levels of serum soluble intercellular adhesion molecule 1 (sICAM-1) in patients with polymyalgia rheumatica (PMR) and/or giant cell arteritis (GCA) prior and during steroid therapy. METHODS: Sixteen patients with PMR and/or GCA had complete clinical and laboratory investigations at diagnosis before treatment and 9 patients were followed during 6 months of steroid therapy. Serum sICAM-1 levels were measured by ELISA: RESULTS: Serum ICAM-1 levels were higher in the patient group compared to a control population. No significant correlation was found between serum sICAM-1 levels and other indices of disease activity. After steroid administration, a dramatic fall in serum sICAM-1 levels was observed at the end of the first week and persisted until the end of the study period, paralleling clinical and laboratory disease remission. CONCLUSION: Serum sICAM-1 levels paralleled disease activity in PMR and/or GCA. Steroid treatment induced a rapid normalization of the serum sICAM-1 levels.

Aged

Serum soluble CD4 and CD8 levels in polymyalgia rheumatica.

OBJECTIVE: Soluble CD4 (sCD4) and sCD8 were measured in the sera of 19 patients with active polymyalgia rheumatica (PMR). METHODS: We correlated the results obtained with lymphocyte subpopulations, soluble interleukin 2 receptors (sIL-2R), and clinical and laboratory variables at diagnosis. In addition 15 patients were prospectively studied during a 6 month period of prednisone therapy. Assays of the sCD4 and sCD8 molecules and of the sIL-2R were performed using an enzyme-linked immunosorbent kit. RESULTS: Serum sCD8 and sIL-2R levels were significantly elevated in patients with active disease compared to normal controls, while serum sCD4 and the relative percentage of CD8+ T cell levels decreased. In the 15 patients prospectively studied sCD8 levels fell significantly after 1 week of therapy along with the remission of clinical disease and normalization of erythrocyte sedimentation rate. At the end of the study period, sCD8 values did not differ from normal controls and they were significantly reduced compared to baseline values. CD8+ lymphopenia persisted at the end of the study. sCD4 levels remained significantly lower during the study period. sIL-2R levels fell significantly at the end of the study period. However, the 6-month levels of sIL-2R remained significantly higher compared to controls. CONCLUSION: The rise of serum sCD8 levels observed in patients with PMR with active disease suggests an early activation of CD8 T cells. The therapeutic effect of steroid in PMR may be partially mediated by its effect on CD8 activated cells.

Aged

Lymphocyte subpopulations analysis in peripheral blood in polymyalgia rheumatica/giant cell arteritis.

The phenotypic characteristics of peripheral blood lymphocytes were investigated in 22 patients suffering from active polymyalgia rheumatica/giant cell arteritis (PMR/GCA) prior to steroid treatment. We observed a significant reduction in the absolute number and the relative percentage of CD4-, CD8+ and CD3+, CD16+ and/or CD56+ cells compared to controls. Fifteen patients were investigated prospectively over a 6-month period of prednisone therapy. At the end of the study CD4-CD8+ cells had increased significantly compared to baselines, CD3+ CD16+ and/or CD56+ cells remained significantly lower when compared to controls. We did not observe any abnormalities in the absolute number and percentage of HLA-DR+ T lymphocytes, CD5+ B cells and NK cell phenotypes before or during steroid treatment. Our study confirms that there was significant increase in the absolute number of CD8+ T cells during steroid treatment in the PMR/GCA patients, but indicates the persistence of an immunological alteration despite the control of disease manifestations.

Aged