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Biomedical subjects

P Caramaschi

Publications and source records attributed to P Caramaschi.

At least 19 recordsLinked to original sources

Lack of association between three vascular endothelial growth factor gene polymorphisms and systemic sclerosis: results from a multicenter EUSTAR study of European Caucasian patients.

INTRODUCTION: Systemic sclerosis (SSc) is characterised by disturbed vessel morphology and an overproduction of vascular endothelial growth factor (VEGF). The VEGF gene located on chromosome 6p21.3 has several polymorphisms. OBJECTIVE: To test the hypothesis that disturbed angiogenesis may be related to the genetic background of the VEGF gene. MATERIALS AND METHODS: EUSTAR centres included European Caucasian patients with SSc and matched controls with osteoarthritis. The VEGF gene was genotyped by polymerase chain reaction, followed by restriction enzyme analysis. The 634 C/T and 936 C/G mutations and an 18-base pair insertion/deletion at -2549 of the VEGF promoter region were tested. RESULTS: 416 patients with SSc and 249 controls were included in the study population. Of the patients with SSc, 42% had a diffuse cutaneous subtype, 16% had increased pulmonary arterial pressure and 61% had decreased carbon monoxide diffusion capacity. The genotype frequencies in the patients with SSc and in controls were in Hardy-Weinberg equilibrium. The allele and genotype frequencies of the polymorphisms did not differ between patients with SSc and controls. No association was found between these polymorphisms and disease phenotypes. CONCLUSION: This study shows that there is no association between the three selected functional VEGF polymorphisms and SSc.

Adult↗

Levels of F2-isoprostanes in systemic sclerosis: correlation with clinical features.

OBJECTIVE: 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-F2alpha, an F2-isoprostane, and a product of free radical-mediated peroxidation of arachidonic acid. METHODS: 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-F2alpha was measured in all scleroderma patients and in the 43 age- and sex-matched healthy controls. RESULTS: Urinary levels of 8-isoprostaglandin-F2alpha were higher in scleroderma patients than in the healthy control group (341.7 vs 147.6 pg/mg creatinine; P < 0.001). Values of 8-isoprostaglandin-F2alpha were strongly correlated with the nailfold videocapillaroscopy pattern and lung involvement (P = 0.002 and 0.003, respectively), showing increasing levels with the progression of pulmonary severity. Correlation between 8-isoprostaglandin-F2alpha level and von Willebrand factor narrowly failed to reach statistical significance (P = 0.05). There was no correlation between 8-isoprostaglandin-F2alpha concentration and disease activity, vascular, skin and heart involvement, disease pattern or autoantibody profile. CONCLUSIONS: 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.

Adult↗

[Celiac disease and spontaneous abortion].

BACKGROUND: Over the last ten years it has become clear that the clinical expression of celiac disease is more heterogeneous than was thought in the past. Although celiac disease is a relatively frequent disease (1/170-200), it is only diagnosed in a small percentage of adult cases compared to the real situation because it is manifested with few symptoms or in an atypical form, or occasionally is completely silent. Gynecological problems have been reported in women with celiac disease, in particular delayed menarche, early menopause, sterility, recurrent abortion and fetal intrauterine growth retardation. The main aim of this study was to investigate the association between celiac disease and abortion, and in particular to evaluate whether patients suffering from recurrent spontaneous abortion might present an atypical or subclinical form of the disease. METHODS: During the period 1997-1998 a series of laboratory tests were carried out at the Department of Obstetrics and Gynecology and at the Institute of Medicine B of Verona University, in a sample of 184 women (149 from the Obstetrics Clinic and 35 from Internal Medicine B ). These tests included circulating anti-gliadin (AGA) and anti-endomysium (EMA) antibodies and total serum immunoglobulins. In positive cases, further diagnostic tests were performed using small bowel biopsy specimens. RESULTS: In our selected sample of cases, 5 women (2.7%) were positive for immunological screening against IgA-EMA and for bowel biopsy (confirmed diagnosis of celiac disease). Four of these women (2.1%) formed part of a group of patients with a positive history of spontaneous abortion and one (0.5%) was from the control group. CONCLUSIONS: An analysis of the cases that emerged from this study and those reported in the literature shows that tests to identify the celiac disease should be extended to the population with a risk of developing this disease. These subjects should include those with a family history or clinical symptoms, in particular women with a history of multiple abortions. In these cases, there are grounds for suspecting an atypical form of celiac disease.

Abortion, Habitual↗

Mucosa-associated lymphoid tissue lymphoma of the salivary glands occurring in patients affected by Sjögren's syndrome: report of 6 cases.

OBJECTIVE: Mucosa-associated lymphoid tissue (MALT) lymphoma of the salivary glands occurring in 6 patients affected by primary Sjögren's syndrome is reported. METHODS: Clinical findings, histologic type, stage, treatment and outcome of the 6 patients have been revised. RESULTS: In all 6 cases the lymphoma was of the MALT type. Four patients had stage IE disease, 1 patient had stage IIE disease and 1 patient had stage IV disease. The patients received different treatments resulting in all cases in prolonged remission. After 7 years of complete remission 1 patient developed a diffuse large B-cell lymphoma. CONCLUSION: MALT lymphoma of the salivary glands is an indolent disease. Though the best therapy of this lymphoproliferative disorder remains to be established, prolonged remission has been obtained in our cases with different therapeutic approaches. We review the literature regarding the relationship between Sjögren's syndrome and MALT lymphomas and study the mechanisms which may be involved in the transformation from a lymphoepithelial lesion into a neoplastic disorder.

Adult↗

Efficacy of methotrexate in the treatment of ankylosing spondylitis: a three-year open study.

The aim of the study was to evaluate the efficacy of methotrexate treatment in patients with ankylosing spondylitis in a 3-year open trial. Seventeen patients, 14 men and three women (mean age 32.7+/-8.9 years), suffering from ankylosing spondylitis and non-responders to treatment with sulphasalazine, were enrolled in our study. Sixteen of them were evaluable at the end of the study. Methotrexate (7.5-10 mg/week) was administered for 3 years. Efficacy was evaluated on the basis of clinical and laboratory variables, radiographic signs of disease progression and daily dosage of indomethacin. We obtained a good and relatively prompt clinical response except for peripheral arthritis and iridocyclitis; in fact, after 3 months of methotrexate treatment a significant amelioration of the following parameters was observed: visual analogue scale for the evaluation of both night pain and general well-being, Shober's test, occiput-wall distance, fingertip to floor, erythrocyte sedimentation rate, C-reactive protein level and daily dose of indomethacin. A further improvement was obtained during the subsequent period. Radiographs of the spine and sacroiliac joints did not show any signs of disease progression. Side-effects were a transitory elevation of transaminases (four cases) and slight hypogammaglobulinaemia (one case). Methotrexate treatment may be useful in ankylosing spondylitis, but a combined treatment might be indicated for patients with peripheral arthritis.

Adult↗

Unsuccessful treatment with fludarabine in four cases of refractory rheumatoid arthritis.

The aim of this study was to evaluate the efficacy of fludarabine treatment in patients suffering from refractory rheumatoid arthritis. Four patients affected by refractory seropositive rheumatoid arthritis underwent treatment with fludarabine for 6 months. The drug was administered intravenously at a dose of 25 mg the first month in a single infusion, and then monthly for 5 months at a dose of 25 mg for 3 consecutive days. All four patients obtained no clinical benefit from the treatment; moreover, inflammation indices worsened and the prednisone dosage was increased during the trial, in spite of a significant fall in CD4+ T cells. In our experience low-dose fludarabine is not useful in the treatment of refractory rheumatoid arthritis.

Arthritis, Rheumatoid↗

Combination therapy with hydroxychloroquine, gold sodium thiomalate and methotrexate in early rheumatoid arthritis. An open 3-year study.

During recent years, aggressive therapeutic approaches have been proposed in order to control the Rheumatoid Arthritis (RA) activity and to avoid joint destruction. Here we report the results of an open 3-year trial on the combination of three second-line drugs, hydroxychloroquine (HCQ), methotrexate (MTX) and gold sodium thiomalate (GST), in early active RA. Four men and 17 women were enrolled in the study and were treated during the first year with HCQ 400 mg/day, GST 50 mg/week and oral MTX 7.5 mg/week; during the second and the third years the doses of HCQ and MTX were reduced to 200 mg/day and 5 mg/week, respectively; the interval between the GST injections was progressively increased until 4 weeks. Prednisone at an initial dose not higher than 10 mg/day was associated. Sulindac was allowed. Eight patients left the study because of side-effects, 2 patients abandoned the study, 12 patients compleated the 3 years of treatment. We obtained a significant and early amelioration of both clinical and laboratory parameters during the first year; in the two subsequent years the positive results were maintained. In our opinion the most significant result is the absence of anatomical progression in 10 out of 12 patients, even if a more prolonged observation is necessary to obtain more reliable data.

Adult↗

[Celiac disease and abortion: focusing on a possible relationship].

Celiac disease represents one of the most frequent chronic inflammatory diseases. In Italy the prevalence among school-age population has been calculated in 1:180 subjects. Along with typical forms of the disease characterized by overt symptoms and signs of malabsorption, many cases are undiagnosed because they are subclinical, atypical or even symptomless. In adults, the disease may present with infertility; in particular celiac disease may be responsible of multiple abortions. These manifestations, whose pathogenesis is unknown, are not related to the severity of the disease; the gluten-free diet strongly ameliorates the fertility. In this paper we have focused the connection between abortion and celiac disease. A better knowledge of this relationship may lead to correctly diagnose and consequently to treat the cause of some cases of abortion, previously labelled as cases of unidentified origin.

Abortion, Spontaneous↗

[Aspects of thrombophilia in Buerger's disease].

Buerger's disease or thromboangiitis obliterans is a disorder of unknown etiology which affects young heavy smokers, mainly of male sex; it is not clear why this disease afflicts only a little number of heavy smokers. Studies about genetic predisposition, autoimmune phenomena and platelet function have been performed in order to search additional etiologic factors without finding significant alterations. Recently some cases of Buerger's disease in association with hypercoagulable states have been described. The authors reported ten subjects affected by Buerger's disease, who have undergone to a clotting process evaluation. We have found 3 cases with fasting hyperhomocysteinemia in association with low level of plasma folate, 3 cases with high value of lipoprotein(a) (in 1 subject in association with IgG anticardiolipin antibody positivity), 1 case with IgM anticardiolipin antibody positivity. These findings, along with literature data, induce to hypothesize that hypercoagulable states may favour the clinical expression of Buerger's disease.

Adjuvants, Immunologic↗

[Thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus. Clinical diagnosis and therapeutic strategies].

The aim of our work is the focusing on some aspects about both the etiopathogenesis of thrombotic thrombocytopenic purpura and the therapeutic choices required to strongly reduce the mortality. Moreover the article reviews the association between thrombotic thrombocytopenic purpura and systemic lupus erythematosus. Thrombotic thrombocytopenic purpura is a rare and severe hematologic syndrome, first described in 1924, characterized by a clinical pentade: fever, microangiopathic anemia, thrombocytopenia, neurologic abnormalities and renal involvement. It is unknown if the endothelial damage represents the first lesion or if the platelet hyperaggregability precedes the vascular injury. Some data suggest a possible role of immune mechanisms in the development of the disease, that may be associated in some cases with autoimmune disorders. To our knowledge 31 cases of association between thrombotic thrombocytopenic purpura and systemic lupus erythematosus are reported in the English literature from 1970 today; the link between the two diseases is unclear. The authors review these cases with particular care to the diagnosis, that may be very difficult, and the therapy.

Autoimmune Diseases↗

Expression of FCepsilonII/CD23 on human neutrophils isolated from rheumatoid arthritis patients.

CD23, the low affinity receptor for IgE, is a 45 kilodalton molecule belonging to the C-type lectin family, some members of which have been identified as adhesion molecules. Since it has been described upregulated in different cells in chronic inflammatory diseases and in rheumatoid arthritis in particular, where neutrophils are directly involved in tissue damage, our interest, in this work, has been focused on the expression and regulation of this antigen on neutrophil membrane. We studied 22 patients suffering from rheumatoid arthritis and 22 healthy control subjects. CD23 expression on neutrophil membrane was analyzed by immunofluorescence. Neutrophils of 9 out of 22 patients expressed CD23 molecules, neutrophils of 11 out of 22 patients expressed CD23 only after 24 h of incubation in RPMI; only 2 out of 22 patients did not express the CD23 antigen on neutrophil membrane either after isolation or after a 24 h incubation. On the contrary neutrophils isolated from healthy subjects did not express CD23 molecules upon isolation. Only in 7/22 control subjects neutrophils resulted positive after 24 h of incubation in RPMI. Moreover, we found that in our experimental conditions the presence of IFN-g or GM-CSF alone or in combination with IL-4 inhibited CD23 expression during the 24 h incubation. Our results show that there is a strong association between neutrophil ability to express CD23 and rheumatoid arthritis, and that such expression may be regulated by GM-CSF, IFN-gamma and IL-4.

Adult↗

Neutrophil migration, oxidative metabolism and adhesion in early onset periodontitis.

The aim of this study was to evaluate neutrophil function in patients suffering from the generalized form of early onset periodontitis (EOP). We investigated neutrophil migration in vivo and neutrophil superoxide production and adhesion in response to a variety of compounds; neutrophils were isolated both from blood and a skin experimental exudate of 15 patients with EOP and of 15 sex- and age-matched normal control subjects. No difference was found in neutrophil migration in vivo (71.2+/-16.4x10(6) and 68.8+/-10.7x10(6) PMN/cm2/24 h in patients affected by early onset periodontitis and normal subjects respectively) and in adhesion. The superoxide production in response to STZ and PMA was similar between the 2 groups, while superoxide production in response to fMLP was markedly lower in patients than in control subjects both in circulating neutrophils (5.6+/-2.2 versus 10.4+/-2.3 nmoles O2-/10(6) cells, p<0.0001) and in exudate neutrophils (16.3+/-4.3 versus 22.3+/-4.7 nmoles O2-/10(6) cells, p<0.005). In general, neutrophil function in patients suffering from early onset periodontitis does not differ from control subjects, suggesting that the overall defence function of these cells is normal. The only parameter that we have found to be different between the 2 groups is the low superoxide production after fMLP stimulation. The stimulus- and function-specificity of this defect in neutrophils from patients indicates the existence of a dysregulation of the signal transduction pathway distal to fMLP receptor and proximal to NADPH oxidase activation.

Adult↗