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Biomedical subjects

A Gabrielli

Publications and source records attributed to A Gabrielli.

At least 127 records · Page 7Linked to original sources
PubMedDate not supplied

Coagulative modifications in patients with systemic sclerosis treated with iloprost or nifedipine.

This study compared iloprost and nifedipine to ascertain whether they could improve parameters of endothelial and platelet functions in the treatment of Raynaud's phenomenon secondary to systemic sclerosis. Thirteen patients affected by systemic sclerosis were treated with intravenous infusion of iloprost, and 7 patients were treated with oral nifedipine. Blood samples were taken at baseline and after 6 and 12 months of therapy to assess main serological indexes of endothelial damage, thrombin activation, fibrinolysis, as well as natural inhibitors of coagulation. After 12 months of therapy, the patients treated with iloprost had a significant decrease in thrombomodulin levels (p = 0.02) and a significant increase in tissue-plasminogen activator levels (p = 0.007), in comparison with the patients taking nifedipine (p = 0.007). Moreover, patients treated with nifedipine showed increased levels of thrombin-antithrombin complex after 12 months of therapy in comparison with baseline values (p = 0.03) and in comparison with the values of the patients treated with iloprost over the same period (p = 0.05). These preliminary results thus seem to indicate that iloprost plays an important, if at least partial, role in the protection and restoration of endothelial integrity in patients with systemic sclerosis.

Blood Coagulation↗
PubMedDate not supplied

Hepatitis B virus-related markers in secondary and in essential mixed cryoglobulinemias: a multicentric study of 596 cases. The Italian Group for the Study of Cryoglobulinemias (GISC).

The aim of this study was to assess the prevalence of HBV-related markers in cryoglobulinemias and the possible association between hepatitis B virus (HBV) and essential mixed cryoglobulinemia (EMC). A retrospective survey of the prevalence of HBV infection in cryoglobulinemic patients was carried out in 596 cases of cryoglobulinemia. On the basis of clinical and laboratory criteria the cases were grouped as secondary to connective tissue disease, to lymphoproliferative disorders, to chronic liver diseases or to chronic infectious diseases. The cases in which an associated disease was not evidenced were considered as essential mixed cryogobulinemias. Subjects in which liver dysfunction was first diagnosed simultaneously with cryoglobulinemia, were considered as a separate group. A greater prevalence of HBsAg and anti-HBc antibodies was found in cryoglobulinemias secondary to chronic liver disease (p < 0.0001) and in those associated with liver involvement at diagnosis (p < 0.05) than that found in EMCs. The prevalence of anti-HBs antibodies did not differ significantly among the groups. Proven contact with the virus, documented by at least one positive marker, was evidenced more frequently in cryoglobulinemias secondary to liver disease than in the other groups (p < 0.01). The prevalence of HBV related markers in EMCs and in hospitalized patients not suffering from diseases associated with cryoglobulin production were similar, and seems to reflect the epidemiological situation of HBV infection in Italy. In conclusion, our findings do not support an association of HBV with EMC.

Biomarkers↗
PubMedDate not supplied

Antibodies against terminal galactosyl (alpha 1-3) galactose epitopes in systemic sclerosis (scleroderma).

Sera from 224 patients with systemic sclerosis (scleroderma) were analyzed for circulating antibodies against an antigenic determinant characterized by two molecules of galactose in alpha 1-3 linkage. About 45% of the patients were found to have values above the normal range. The mean antibody level was significantly higher than that found in normal subjects (p less than 0.001) or in patients with primary Raynaud's phenomenon who were included as controls. The mean level of anti-Gal antibodies correlated with the degree of skin and internal organ involvement, as well as with the presence of progression or inflammation. Furthermore, when patients with early onset disease were analyzed, high levels of anti-Gal antibodies were present in the subgroups characterized by evidence of progression or inflammation, whereas patients with stable disease did not differ from the controls. We conclude that humoral immunity against Gal alpha 1-3 Gal is an early feature of scleroderma, may be important for its pathogenesis, and may provide a more sensitive tool to detect disease activity.

Adolescent↗
PubMedDate not supplied

Serological assessment of type I collagen burden in scleroderma spectrum disorders: a systematic review.

RATIONALE: The aim of the study was to evaluate the validity of collagen type I metabolites as markers of disease activity in scleroderma (SSc), through a systematic review of the literature and by validating the results by measuring collagen type I metabolites in well characterized patients with scleroderma spectrum disorders and in Raynaud's phenomenon. METHODS: A systematic review was performed of studies of collagen type I metabolites in scleroderma spectrum disorders published from 1980 to 2003. The collected results from the literature were compared with our own measurements of collagen type I metabolites (PINP and ICTP) in a small number of well characterized patients within the scleroderma spectrum and in patients with primary and "autoimmune" Raynaud's phenomenon. Peptide concentrations from all sources, including the present study, were compared. Reported correlations between peptide concentrations and clinical variables were also analysed. RESULTS: Of 19 papers identified by an extensive Medline search, 12 were eligible for systematic analysis. There was a considerable heterogeneity in the results with a wide range of metabolite concentrations. Values from disease groups and healthy controls overlapped. These findings were confirmed by our study where, similarly, there was a large range of values in all groups, but particularly in the diffuse SSc subset. When the correlation between peptide levels and clinical variables was assessed, large discordance between the studies was observed. CONCLUSIONS: We have not found sufficient evidence to support the use of serum markers of collagen turnover in the assessment of scleroderma activity and severity, in view of their low specificity and the heterogeneity of the results of various studies. Lack of standardized routine evaluation of SSc patients in clinical studies might have accounted for the variability of the findings. However, due to the small sizes of most published studies, demonstration of no effect should come from large-scale randomised trials. Longitudinal serial analysis of these molecules in individual patients may play a future role in the evaluation of the response to fibroblast-targeting therapeutic strategies in scleroderma patients.

Biomarkers↗
PubMedDate not supplied

Scleroderma fibroblasts constitutively express the long pentraxin PTX3.

OBJECTIVE: PTX3 is a secreted molecule which consists of a C-terminal domain similar to classical pentraxins (e.g. C-reactive protein) and of an unrelated N-terminal domain. Unlike the classical pentraxins, PTX3 is expressed in response to IL-1beta and TNF-alpha but not to IL-6. The present study was designed to investigate the expression of PTX3 in normal and scleroderma fibroblasts. METHODS: Normal and SSc fibroblasts were cultured in the presence and absence of inflammatory cytokines. PTX3 mRNA expression in fibroblasts was evaluated by Northern analysis. PTX3 protein levels in fibroblast culture medium were estimated by ELISA. RESULTS: Normal fibroblasts were induced to express high levels of P7X3 mRNA by IL-1beta and TNF-alpha but not by other cytokines or growth factors. Scleroderma fibroblasts, unlike normal fibroblasts, constitutively expressed high levels of PTX3 in the absence of deliberate stimulation. The constitutive expression of PTX3 in SSc fibroblasts was not modified by anti-TNF-alpha antibodies or IL-1 receptor antagonist. In contrast, IFN-gamma and TGF-beta inhibited the constitutive but not the stimulated expression of PTX3 in SSc fibroblasts. CONCLUSIONS: PTX3 is a main feature of activated scleroderma fibroblasts.

C-Reactive Protein↗
PubMedDate not supplied

The fibrinolytic system components are increased in systemic sclerosis and modulated by Alprostadil (alpha1 ciclodestryn).

OBJECTIVES: To evaluate urokinase plasminogen activator (u-PA), urokinase plasminogen activator soluble receptor (su-PAR), plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (t-PA) plasma levels in SSc patients (pts) versus healthy controls and their modulation by intravenous alphacyclodestrine (Alprostadil). METHODS: Plasma levels of u-PA, su-PAR, PAI-1 and t-PA were measured in 40 SSc (34 lSSc and 6 dSSc) pts and in 30 healthy controls. In SSc, blood was drawn before and after 3 consecutive daily of Alprostadil infusion (60 mg in 250 cc NaCl 0.9%). RESULTS: In SSc su-PAR basal levels were higher than controls (7.48 +/- 2.5 vs 4.69 +/- 0.4 ng/ml; p = 0.001) and were significantly reduced by Alprostadil (5.93 +/- 1.7; p = 0.002), but remain higher than controls (p = 0.03). u-PA basal levels were higher than controls (3.78 +/- 1.5 vs 1.29 +/- 0.3 ng/ml; p < 0.001) and were reduced by Alprostadil (2.39 +/- 1.7; p < 0.001) to control levels. SSc PAI-1 basal levels were lower than controls (31.60 +/- 7.7 vs 48.30 +/- 6.8 ng/ml; p < 0.001) and increased by Alprostadil (34.66 +/- 5.4; p = 0.04), but lower than controls (p < 0.001). SSc t-PA basal levels were higher in respect to controls (1645.81 +/- 792.7 vs 571.95 +/- 75.5 pg/ml; p < 0.0001) and reduced by Alprostadil (1318.06 +/- 603.5; p = 0.04), but still higher than controls (p = 0.001). CONCLUSION: Fibrinolysis were increased in SSc. Infusions of Alprostadil modulate u-PA, su-PAR, PAI-1 and t-PA, restoring near normal levels. In SSc, fibrinolysis system may become a potential target for new therapies.

Aged↗
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Use of high-dose intravenous immunoglobulin in systemic lupus erythematosus: report of three cases.

Three patients with life-threatening manifestations of systemic lupus erythematosus (SLE), unresponsive to conventional high-dose corticosteroid and/or immunosuppressive therapy were treated with intravenous polyspecific IgG (IVIG). Following IVIG infusion, lupus encephalitis in the first patient quickly resolved and the impressive improvement of the clinical status was associated with a transient increase in C1q-binding activity. The daily infusion of IgG had to be suspended after three days in the second patient with encephalitis and nephritis, because the renal function rapidly deteriorated; subsequently, six plasma exchanges led to an almost complete recovery. Finally, leukocyte and platelet counts increased and remained within normal range following IgG therapy in the third patient having SLE-associated leuko- and thrombocytopenia. In all three patients a decrease in anti-DNA antibody levels and an increase in total complement hemolytic activity were detected after therapy.

Adolescent↗
PubMedDate not supplied

[Serum levels of total and free tryptophan in the premature newborn infant treated with aminophylline].

Apnea of prematurity in the majority of the cases becomes evident during the nonREM phases of sleep. Aminophylline, one of the most commonly used xantines in prevention, seems to reduce the incidence of these crises, increasing the duration of the REM phase and of the wakefulness of the newborn. It is possible that the serotonin, neuromediator of the REM phase, represents an important element in determining the crises of apnea, conditioned by variation in the serum levels of tryptophan that regulates the synthesis and liberation of cerebral serotonin. Our data demonstrate how aminophylline increases the post-natal physiological diminution of total tryptophan in the preterm. Therefore we can deduce, from our results, that an increased synthesis and liberation of serotonin may to increase the duration of the REM and to reduce the incidence of apnea.

Aminophylline↗
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Eosinophilic fasciitis: a mast cell disorder?

The rarity of eosinophilic fasciitis has so far prevented systematic investigations. Its etiology is still unknown and its nosographical position to be defined. We report here a further case whose distinctive features were: a gradual onset simultaneous with allergic bronchial asthma; the absence of eosinophils and presence of a high number of degranulating mast cells and Sezary-like cells in the inflamed fascia. The follow-up and a second biopsy suggested that early steroid treatment is advisable in these patients.

Adult↗
PubMedDate not supplied

Fish-oil fatty acid supplementation in mixed cryoglobulinemia: a preliminary report.

OBJECTIVE: Since fish oils seem to play a potential role in the treatment of inflammatory disorders by inhibiting arachidonic acid metabolism, the purpose of this study was to determine their therapeutic efficacy in mixed cryoglobulinemia (MC), an inflammatory condition caused by the deposition of immune complexes in vessel walls. METHODS: In an 8-week double-blind randomized trial, ten MC patients received a daily dietary supplement of 3 gm of eicosapentaenoic acid (EPA) and 2 gm of docosahexenoic acid (DHA), while 10 other MC patients received placebo (olive oil). The severity of purpura, arthralgias, paresthesias, asthenia and Raynaud's phenomenon were monitored daily, and serological assays were performed at the beginning of the study, at the end of the treatment period, and after 4 weeks of wash-out. RESULTS: No significant differences were found between the two groups with regard to the clinical symptoms, although the percentage of patients who reported a clinical improvement was higher in the group treated with fish oils. As for the serological parameters, no variation was found in the placebo group, while in the group receiving fish oils a significant decrease in cryocrit and rheumatoid factor levels was observed, which in the case of rheumatoid factor persisted at the end of the wash-out period. CONCLUSIONS: Under the experimental conditions employed in this study, we could not demonstrate a significant improvement in clinical symptoms in patients with mixed cryoglobulinemia treated with fish oils. However, since our results indicated some improvement in the serological parameters potentially involved in the pathogenesis of the disorder, further studies are warranted to establish the optimal dose and duration of fish oil supplementation in the treatment of MC.

Adult↗
PubMedDate not supplied

Diagnostic and therapeutic ERCP in patients with Billroth II gastrectomy.

Diagnostic and therapeutic endoscopic cholangio- pancreatography (ERCP) are more difficult in patients with Billroth II gastrectomy. A six-year experience including 274 ERCP in 175 Billroth II patients is reviewed. Overall diagnostic success-rate was 88.3% while a complete endoscopic treatment could be accomplished in 92.8% when indicated. Endoscopy related morbidity and mortality were 5.1% and 0 respectively, while in-hospital mortality was 2.3%. Diagnostic and therapeutic ERCP techniques in Billroth II patients are then discussed with special reference to the choice of the scope and of the accessories to perform a safe endoscopic sphincterotomy. The use of the lateral-viewing duodenoscope and of the long-nose sigmoid inverted sphincterotome (originally modified by our group) are emphasized. ERCP and endoscopic sphincterotomy in Billroth II subjects are today as safe and nearly as effective as in the non-gastrectomized patient.

Adult↗
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Endoscopic diagnosis and treatment of malignant biliary strictures: review of 505 patients.

The role of ERCP and endoscopic drainage in the diagnosis and treatment of patients with malignant biliary obstruction is well established. Endoscopic drainage is an effective therapy for palliation of malignant obstructive jaundice and does not preclude definitive treatment in appropriate candidate. We report our experience, in a retrospective review, of 505 patients with malignant biliary obstruction. In this series, endoscopic biliary drainage is shown to be safe and effective management for these patients. Relief of obstruction was obtained in a large majority of patients with a low, procedure related, morbidity and mortality. We conclude that ERCP, to diagnose and localize obstructive lesions, followed by endoscopic biliary drainage can be strongly considered in all patients with suspected malignant obstructive jaundice.

Adolescent↗
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Humoral immune response and natural killer activity in patients with mixed cryoglobulinemia.

OBJECTIVE: Based on serological and molecular evidence of hepatitis C virus (HCV) infection in a significant proportion of patients with mixed cryoglobulinemia (MC), a direct association between HCV and MC has been suggested. The goal of the present study was to investigate the role played by HCV and by the immune response to the virus in the pathogenesis of mixed cryoglobulinemia. METHODS: A competitive reverse transcription polymerase chain reaction was employed to evaluate the concentrations of specific HCV RNA sequences in different clinical specimens (plasma, sera, cryoprecipitates, bone marrow and peripheral blood cells). Using recombinant and synthetic peptides covering the HCV core, envelope 1 (E1) and nonstructural regions 4 (NS4) and 5 (NS5), the humoral immune response in a group of MC patients was assessed with an enzyme-linked immunosorbent assay. Natural killer (NK) cell activity was estimated using a 4 hr 51 Cr release assay. RESULTS: Quantitation of the RNA molecules in the biological samples confirmed an increased virion concentration in cryoprecipitates from 13/15 patients with mixed cryoglobulinemia. Analysis of the humoral immune response against the synthetic peptides suggested a distinct response to HCV antigens in MC patients when compared to patients with HCV infection but without serological evidence of cryoglobulinemia. Unstimulated NK cell functioning was below the normal range in all patients tested. However, peripheral blood mononuclear cells showed no enhancement of NK activity by the interferon inducer polyinosinic acid:polycytidilic acid. Enhancement by interferon-alpha was normal, suggesting an impairment in interferon production. CONCLUSION: The quantitative data are in line with the hypothesis of a direct or indirect role of HCV in mixed cryoglobulinemia. The abnormal immune response could be involved in the onset and persistence of HCV infection, and possibly in the appearance of cryoglobulinemia.

Antibody Formation↗
PubMedDate not supplied

GISC protocol experience in the treatment of essential mixed cryoglobulinaemia.

OBJECTIVE: We compared the efficacy of interferon and deflazacort in the treatment of the cryoglobulinaemic syndrome and assessed the usefulness of adding a low antigen diet to drug therapy. METHODS: We studied 63 patients randomly allocated to different groups who underwent clinical and laboratory examinations every two months and who received treatment for 12 months or until a significant clinical event appeared. RESULTS: Five of 28 patients treated with interferon showed clinical improvement whereas 4 worsened and 7 suffered untoward side effects; seven of 28 patients treated with deflazacort improved, 4 worsened and 4 suffered drug toxicity. Twenty-nine patients were assigned to combined low antigen diet and therapy, among whom 7 did not follow the diet, 5 improved and 2 worsened. Among the 34 patients who were on an unrestrained diet, 5 improved and 7 worsened. None of the treatments proved superior to the others. CONCLUSION: Our results do not confirm the suggestion that interferon should be the primary therapy in the treatment of the cryoglobulinaemic syndrome, and the usefulness of a low antigen diet seems minimal.

Adult↗