OBJECTIVE Increase of neutrophil chemotaxis in Behçet's disease (BD) has been described, but ... more OBJECTIVE Increase of neutrophil chemotaxis in Behçet's disease (BD) has been described, but it is not clear whether there is a correlation with other variables of neutrophil function and whether these modifications correlate with disease activity. METHODS We studied neutrophil functions in patients with BD in the acute phase in comparison with healthy control subjects and with the same patients during disease remission, with or without therapy. We investigated in vivo neutrophil migration by Senn's skin window technique and measured adhesion assay and superoxide production in circulating and migrating neutrophils after different stimuli. RESULTS Neutrophil migration in vivo was 101.3 +/- 17.9 x 10(6) polymorphonuclear lymphocytes (PMN)/cm2/24 h in patients with BD in the acute phase and 66.1 +/- 7.8 x 10(6) PMN/cm2/24 h in controls (p < 0.001). No correlation was found between leukocyte counts and neutrophil migration. Neutrophil migration evaluated in the same patients ...
Celiac disease represents one of the most frequent chronic inflammatory diseases. In Italy the pr... more 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.
We describe a 68-year old woman affected by chronic hepatitis C virus infection; hypertransaminas... more We describe a 68-year old woman affected by chronic hepatitis C virus infection; hypertransaminasemia was first observed at the age of 46 years, when the patient was diagnosed uterus carcinoma. Since 1994 she had complained of xerostomia, xerophtalmia, pain at the left parotid and laterocervical adenomegaly. Neck ultrasound examination revealed enlarged intraglandular, submandibular and laterocervical lymph nodes. Fine-needle aspiration of both left parotid and laterocervical lymph nodes was not diagnostic. The histologic examination of the surgical biopsy of the left parotid and the right submandibular salivary gland allowed to diagnose mucosa-associated lymphoid tissue lymphoma (MALT lymphoma). The patient was given alpha-interferon obtaining a clinical remission of the lymphoma and transitory normalization of transaminase level. The authors review the literature about some aspects of MALT lymphomas: a) the etiopathogenesis of MALT lymphomas and the mechanisms suspected to be invo...
In literature there are only a few papers about renal involvement in rheumatoid arthritis. The sc... more In literature there are only a few papers about renal involvement in rheumatoid arthritis. The scarcity of reports is due to the difficulties of pinpointing this subject; in fact a bloody investigation like kidney biopsy is necessary to obtain an exact diagnosis. Moreover it is often clinically hard to distinguish renal injury provoked by rheumatoid arthritis from nephropathy caused by drugs, either non steroidal antiinflammatory drugs or disease modifying antirheumatic drugs. This topic is perhaps neglected because primary renal involvement in rheumatoid arthritis is not considered to influence the survival, with the exception of renal amyloidosis. Pathologic examination of kidney biopsy shows in order of frequency: mesangial nephritis, renal amyloidosis, membranous nephritis, focal proliferative nephritis, minimal nephritis, interstitial nephritis. Both immune complexes and antineutrophil cytoplasmic antibodies may play a pathogenetic role. The mesangial nephritis with IgA or IgM ...
Loratadine is a new, highly selective, non sedating, H 1-receptor antagonist, without central ner... more Loratadine is a new, highly selective, non sedating, H 1-receptor antagonist, without central nervous system activity. In a randomized double-blind, crossover study, we evaluated the effects of loratadine and placebo administered once daily in 184 food intolerant patients affected by urticaria-angioedema. The difference between loratadine and placebo treatment was significant in relieving symptoms. Adverse reactions reported in the treatment were mild, in fact somnolence was reported by 3.4%, dry mouth by 2.2% of patients.
European journal of rheumatology and inflammation, 1994
This randomised, double-blind, placebo-controlled, parallel-group trial was carried out to assess... more This randomised, double-blind, placebo-controlled, parallel-group trial was carried out to assess the efficacy and tolerability of a new, locally acting, transcutaneous flurbiprofen preparation (flurbiprofen LATTM, Boots Company PLC) in the treatment of scapulohumeral periarthritis. The new preparation consists of a nonwoven polyester patch supporting a mentholated formulation containing flurbiprofen 40 mg. Eighty patients suffering from the acute, painful phase of scapulohumeral periarthritis entered the trial, three of which failed to provide follow-up data. Each patient applied one patch every 12 hours for the 14 day trial period. Efficacy was assessed in terms of reduction of pain, improvement in shoulder movement and overall clinical assessment of the severity of the condition after treatment. Statistically significant improvements from baseline were observed in both treatment groups, with a constant overall trend in favour of flurbiprofen. The differences between the two treat...
Background Receptors for IgG allow antibody-dependent cell cytotoxicity, and the polymorphism 158... more Background Receptors for IgG allow antibody-dependent cell cytotoxicity, and the polymorphism 158V/F (rs396991) of the Fc fragment of IgG type 3A (FCG3A) was investigated as a genetic factor influencing disease response after rituximab (RTX) therapy in haematologic and rheumatic diseases. Objectives The aim of this study was to better evaluate of the association between 158V/F FCGR3A polymorphism and response to RTX, by analysing a larger series of patients and by dissecting the results at month +4 and at month +6 after treatment. The pharmacogenetic data were also integrated with established clinical predictors of response to RTX in RA, i.e., rheumatoid factor (RF) and/or anti-cyclic citrullinated peptides (anti-CCP) antibodies, baseline DAS28, baseline HAQ, number of TNF blockers previously failed. Methods The study analysed 212 RA patients. Patients were referred to 13 different rheumatologic Centres in Italy. They were unselected and represented the majority of the RA subjects treated with RTX in any single participating centre. Patients were followed for at least 6 months after RTX treatment, from 2004 to 2011, and data were collected after the first cycle of RTX. EULAR response was evaluated at months +4 and +6 after the first RTX infusion. The FCGR3A polymorphism was analysed by PCR followed by Sanger sequencing. Results The FCGR3A genotypes were associated with EULAR response (good or moderate) at month +6 [response in 34/38 (89.5%) VV vs. 70/106 (66%) VF and in 51/77 (66.2%) FF patients; p=0.01], but not at month +4 [response in 32/37 (86.5%) VV vs. 69/102 (67.6%) VF and 53/73 (72.6%) FF patients; p=0.09]. Loss of response was observed only in VF and FF carriers [(VV vs VF vs FF: 0/37 (0%) vs 11/102 (10.8%) vs 12/73 (16.4%); p=0.02)]. Probability of response at month +6 was very high when at least two of the three following items selected by multivariate analysis were present: positive rheumatoid factor and/or anti-CCP antibodies, previous treatment with ≤1 anti-TNF agent, and 158VV FCGR3A genotype (p<0.0001; OR 7.9, 95%CI 4.1-15.1). Conclusions The 158VV FCGR3A genotype was associated with response to RTX in a large cohort of RA patients. Previous results from a similar French study (1) were partially confirmed in an Italian population. Patient genotyping may be helpful to plan RTX treatment, and, notably, may be integrated with clinical predictors. References Ruyssen-Witrand A, et al. FcY receptor type IIIA polymorphism influences treatment outcomes in patients with rheumatoid arthritis treated with rituximab. Ann Rheum Dis. 2012;71:875-7 Disclosure of Interest: None Declared
... 3. Baxter DE, Thigpen CM: Heel pain-operative results, Font Ankle 5; 16-25, 1984. ... 75, 535... more ... 3. Baxter DE, Thigpen CM: Heel pain-operative results, Font Ankle 5; 16-25, 1984. ... 75, 535-537, 1985. 25.JORGENSEN U, BOJSEN-MOLLER F: Shock absorbency of factors in the shoe/heel interation-with special focus on role of the heel pad, Foot Ankle 9: 294-299, 1989. ...
To determine whether homocysteine (Hcy) plasma levels are correlated with molecules indicative of... more To determine whether homocysteine (Hcy) plasma levels are correlated with molecules indicative of endothelial cell and fibroblast activation, including endothelin-1 (ET-1) and monocyte chemoattractant protein-1 and -3 (MCP-1, MCP-3), in patients with systemic sclerosis (SSc). Eighty-two patients were enrolled in this study; the control group included 75 age- and sex-matched subjects. Plasma Hcy was determined by high-performance liquid chromatography; folic acid, and vitamin B(12) plasma levels were determined by a chemiluminescence method. ET-1, MCP-1, and MCP-3 were determined by enzyme-linked immunosorbent assay (ELISA). Analysis of the 677C--&gt;T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene was performed by polymerase chain reaction (PCR) and digestion with the enzyme HinfI. Hcy levels were lower in patients whereas ET-1 was significantly higher in patients and correlated with MCP-1. Stratification of the patients on the basis of Hcy levels was not associated with any statistical difference in the concentration of ET-1, MCP-1, and MCP-3. Patients with diffuse disease presented the highest levels of ET-1 and MCP-1. The distribution of the MTHFR genotypes was not different in patients and controls. In SSc, Hcy plasma concentration does not influence ET-1, MCP-1, or MCP-3 levels. On the contrary, ET-1, a marker of vascular activation, correlates with MCP-1, a chemokine involved in the fibrotic process of SSc.
In this study we investigated the serum levels of a released soluble form of the interleukin-2 re... more In this study we investigated the serum levels of a released soluble form of the interleukin-2 receptor (sIL-2R) in 42 patients with rheumatoid arthritis and in 12 cases of systemic lupus erythematosus. Data were evaluated in relationship to the clinical phase and compared with those observed in normal controls (N = 56) and in osteoarthritis (N = 7). Increased levels were observed in both rheumatoid arthritis (mean +/- SE, 604 +/- 49 U/ml) and systemic lupus erythematosus (1438 +/- 481 U/ml). These values were significantly higher than in control (256 +/- 15 U/ml; P less than 0.001) and in osteoarthritis (298 +/- 33 U/ml; P less than 0.001) groups. In addition, the highest values were associated with the active phases of both rheumatoid arthritis (active vs inactive, 771 +/- 78 vs 451 +/- 39 U/ml; P less than 0.001) and systemic lupus erythematosus (active vs inactive, 2108 +/- 489 vs 499 +/- 75 U/ml; P less than 0.001). Our findings suggest that the detection of sIL-2R in rheumatoid arthritis and in systemic lupus erythematosus may represent a good marker of disease activity, which indirectly indicates the ongoing activation and/or proliferation of immunoreactive cells which are involved in the pathogenetic events of these autoimmune conditions.
OBJECTIVE Increase of neutrophil chemotaxis in Behçet's disease (BD) has been described, but ... more OBJECTIVE Increase of neutrophil chemotaxis in Behçet's disease (BD) has been described, but it is not clear whether there is a correlation with other variables of neutrophil function and whether these modifications correlate with disease activity. METHODS We studied neutrophil functions in patients with BD in the acute phase in comparison with healthy control subjects and with the same patients during disease remission, with or without therapy. We investigated in vivo neutrophil migration by Senn's skin window technique and measured adhesion assay and superoxide production in circulating and migrating neutrophils after different stimuli. RESULTS Neutrophil migration in vivo was 101.3 +/- 17.9 x 10(6) polymorphonuclear lymphocytes (PMN)/cm2/24 h in patients with BD in the acute phase and 66.1 +/- 7.8 x 10(6) PMN/cm2/24 h in controls (p < 0.001). No correlation was found between leukocyte counts and neutrophil migration. Neutrophil migration evaluated in the same patients ...
Celiac disease represents one of the most frequent chronic inflammatory diseases. In Italy the pr... more 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.
We describe a 68-year old woman affected by chronic hepatitis C virus infection; hypertransaminas... more We describe a 68-year old woman affected by chronic hepatitis C virus infection; hypertransaminasemia was first observed at the age of 46 years, when the patient was diagnosed uterus carcinoma. Since 1994 she had complained of xerostomia, xerophtalmia, pain at the left parotid and laterocervical adenomegaly. Neck ultrasound examination revealed enlarged intraglandular, submandibular and laterocervical lymph nodes. Fine-needle aspiration of both left parotid and laterocervical lymph nodes was not diagnostic. The histologic examination of the surgical biopsy of the left parotid and the right submandibular salivary gland allowed to diagnose mucosa-associated lymphoid tissue lymphoma (MALT lymphoma). The patient was given alpha-interferon obtaining a clinical remission of the lymphoma and transitory normalization of transaminase level. The authors review the literature about some aspects of MALT lymphomas: a) the etiopathogenesis of MALT lymphomas and the mechanisms suspected to be invo...
In literature there are only a few papers about renal involvement in rheumatoid arthritis. The sc... more In literature there are only a few papers about renal involvement in rheumatoid arthritis. The scarcity of reports is due to the difficulties of pinpointing this subject; in fact a bloody investigation like kidney biopsy is necessary to obtain an exact diagnosis. Moreover it is often clinically hard to distinguish renal injury provoked by rheumatoid arthritis from nephropathy caused by drugs, either non steroidal antiinflammatory drugs or disease modifying antirheumatic drugs. This topic is perhaps neglected because primary renal involvement in rheumatoid arthritis is not considered to influence the survival, with the exception of renal amyloidosis. Pathologic examination of kidney biopsy shows in order of frequency: mesangial nephritis, renal amyloidosis, membranous nephritis, focal proliferative nephritis, minimal nephritis, interstitial nephritis. Both immune complexes and antineutrophil cytoplasmic antibodies may play a pathogenetic role. The mesangial nephritis with IgA or IgM ...
Loratadine is a new, highly selective, non sedating, H 1-receptor antagonist, without central ner... more Loratadine is a new, highly selective, non sedating, H 1-receptor antagonist, without central nervous system activity. In a randomized double-blind, crossover study, we evaluated the effects of loratadine and placebo administered once daily in 184 food intolerant patients affected by urticaria-angioedema. The difference between loratadine and placebo treatment was significant in relieving symptoms. Adverse reactions reported in the treatment were mild, in fact somnolence was reported by 3.4%, dry mouth by 2.2% of patients.
European journal of rheumatology and inflammation, 1994
This randomised, double-blind, placebo-controlled, parallel-group trial was carried out to assess... more This randomised, double-blind, placebo-controlled, parallel-group trial was carried out to assess the efficacy and tolerability of a new, locally acting, transcutaneous flurbiprofen preparation (flurbiprofen LATTM, Boots Company PLC) in the treatment of scapulohumeral periarthritis. The new preparation consists of a nonwoven polyester patch supporting a mentholated formulation containing flurbiprofen 40 mg. Eighty patients suffering from the acute, painful phase of scapulohumeral periarthritis entered the trial, three of which failed to provide follow-up data. Each patient applied one patch every 12 hours for the 14 day trial period. Efficacy was assessed in terms of reduction of pain, improvement in shoulder movement and overall clinical assessment of the severity of the condition after treatment. Statistically significant improvements from baseline were observed in both treatment groups, with a constant overall trend in favour of flurbiprofen. The differences between the two treat...
Background Receptors for IgG allow antibody-dependent cell cytotoxicity, and the polymorphism 158... more Background Receptors for IgG allow antibody-dependent cell cytotoxicity, and the polymorphism 158V/F (rs396991) of the Fc fragment of IgG type 3A (FCG3A) was investigated as a genetic factor influencing disease response after rituximab (RTX) therapy in haematologic and rheumatic diseases. Objectives The aim of this study was to better evaluate of the association between 158V/F FCGR3A polymorphism and response to RTX, by analysing a larger series of patients and by dissecting the results at month +4 and at month +6 after treatment. The pharmacogenetic data were also integrated with established clinical predictors of response to RTX in RA, i.e., rheumatoid factor (RF) and/or anti-cyclic citrullinated peptides (anti-CCP) antibodies, baseline DAS28, baseline HAQ, number of TNF blockers previously failed. Methods The study analysed 212 RA patients. Patients were referred to 13 different rheumatologic Centres in Italy. They were unselected and represented the majority of the RA subjects treated with RTX in any single participating centre. Patients were followed for at least 6 months after RTX treatment, from 2004 to 2011, and data were collected after the first cycle of RTX. EULAR response was evaluated at months +4 and +6 after the first RTX infusion. The FCGR3A polymorphism was analysed by PCR followed by Sanger sequencing. Results The FCGR3A genotypes were associated with EULAR response (good or moderate) at month +6 [response in 34/38 (89.5%) VV vs. 70/106 (66%) VF and in 51/77 (66.2%) FF patients; p=0.01], but not at month +4 [response in 32/37 (86.5%) VV vs. 69/102 (67.6%) VF and 53/73 (72.6%) FF patients; p=0.09]. Loss of response was observed only in VF and FF carriers [(VV vs VF vs FF: 0/37 (0%) vs 11/102 (10.8%) vs 12/73 (16.4%); p=0.02)]. Probability of response at month +6 was very high when at least two of the three following items selected by multivariate analysis were present: positive rheumatoid factor and/or anti-CCP antibodies, previous treatment with ≤1 anti-TNF agent, and 158VV FCGR3A genotype (p<0.0001; OR 7.9, 95%CI 4.1-15.1). Conclusions The 158VV FCGR3A genotype was associated with response to RTX in a large cohort of RA patients. Previous results from a similar French study (1) were partially confirmed in an Italian population. Patient genotyping may be helpful to plan RTX treatment, and, notably, may be integrated with clinical predictors. References Ruyssen-Witrand A, et al. FcY receptor type IIIA polymorphism influences treatment outcomes in patients with rheumatoid arthritis treated with rituximab. Ann Rheum Dis. 2012;71:875-7 Disclosure of Interest: None Declared
... 3. Baxter DE, Thigpen CM: Heel pain-operative results, Font Ankle 5; 16-25, 1984. ... 75, 535... more ... 3. Baxter DE, Thigpen CM: Heel pain-operative results, Font Ankle 5; 16-25, 1984. ... 75, 535-537, 1985. 25.JORGENSEN U, BOJSEN-MOLLER F: Shock absorbency of factors in the shoe/heel interation-with special focus on role of the heel pad, Foot Ankle 9: 294-299, 1989. ...
To determine whether homocysteine (Hcy) plasma levels are correlated with molecules indicative of... more To determine whether homocysteine (Hcy) plasma levels are correlated with molecules indicative of endothelial cell and fibroblast activation, including endothelin-1 (ET-1) and monocyte chemoattractant protein-1 and -3 (MCP-1, MCP-3), in patients with systemic sclerosis (SSc). Eighty-two patients were enrolled in this study; the control group included 75 age- and sex-matched subjects. Plasma Hcy was determined by high-performance liquid chromatography; folic acid, and vitamin B(12) plasma levels were determined by a chemiluminescence method. ET-1, MCP-1, and MCP-3 were determined by enzyme-linked immunosorbent assay (ELISA). Analysis of the 677C--&gt;T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene was performed by polymerase chain reaction (PCR) and digestion with the enzyme HinfI. Hcy levels were lower in patients whereas ET-1 was significantly higher in patients and correlated with MCP-1. Stratification of the patients on the basis of Hcy levels was not associated with any statistical difference in the concentration of ET-1, MCP-1, and MCP-3. Patients with diffuse disease presented the highest levels of ET-1 and MCP-1. The distribution of the MTHFR genotypes was not different in patients and controls. In SSc, Hcy plasma concentration does not influence ET-1, MCP-1, or MCP-3 levels. On the contrary, ET-1, a marker of vascular activation, correlates with MCP-1, a chemokine involved in the fibrotic process of SSc.
In this study we investigated the serum levels of a released soluble form of the interleukin-2 re... more In this study we investigated the serum levels of a released soluble form of the interleukin-2 receptor (sIL-2R) in 42 patients with rheumatoid arthritis and in 12 cases of systemic lupus erythematosus. Data were evaluated in relationship to the clinical phase and compared with those observed in normal controls (N = 56) and in osteoarthritis (N = 7). Increased levels were observed in both rheumatoid arthritis (mean +/- SE, 604 +/- 49 U/ml) and systemic lupus erythematosus (1438 +/- 481 U/ml). These values were significantly higher than in control (256 +/- 15 U/ml; P less than 0.001) and in osteoarthritis (298 +/- 33 U/ml; P less than 0.001) groups. In addition, the highest values were associated with the active phases of both rheumatoid arthritis (active vs inactive, 771 +/- 78 vs 451 +/- 39 U/ml; P less than 0.001) and systemic lupus erythematosus (active vs inactive, 2108 +/- 489 vs 499 +/- 75 U/ml; P less than 0.001). Our findings suggest that the detection of sIL-2R in rheumatoid arthritis and in systemic lupus erythematosus may represent a good marker of disease activity, which indirectly indicates the ongoing activation and/or proliferation of immunoreactive cells which are involved in the pathogenetic events of these autoimmune conditions.
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