Biomedical subjects

Luigi Boiardi

Publications and source records attributed to Luigi Boiardi.

At least 19 recordsLinked to original sources

PubMed2006

Interleukin-10 promoter polymorphisms in giant cell arteritis.

OBJECTIVE: To investigate potential associations between interleukin-10 (IL-10) promoter polymorphisms and susceptibility to, and clinical features of, giant cell arteritis (GCA). METHODS: A total of 140 patients with biopsy-proven GCA who were residents of Reggio Emilia, Italy, and 200 population-based controls from the same geographic area were genotyped for promoter polymorphisms of the IL-10 gene, by molecular methods. The patients were subgrouped according to the presence or absence of polymyalgia rheumatica (PMR) and ischemic complications (any or all of the following: vision loss, jaw claudication, cerebrovascular accidents, or aortic arch syndrome). RESULTS: The distribution of the C/A 592 genotype differed significantly between the GCA patients and the controls (P(corr) = 0.003). Carriers of the A592 allele (A/A or C/A) were significantly more frequent among the GCA patients than among the controls (P(corr) = 0.004, odds ratio [OR] 2.0 [95% confidence interval (95% CI) 1.3-3.1]). Homozygosity for the A592 allele was significantly more frequent among the GCA patients than among the controls (P(corr) = 0.002, OR 3.4 [95% CI 1.6-7.2]). The distribution of the A/G 1082 genotype was similar in GCA patients and controls. In the haplotype analysis, the frequency of the ATA haplotype was significantly higher in GCA patients than in the controls (P = 0.0001), whereas the frequencies of the ACC and GTA haplotypes were significantly lower (P = 0.0001 for both comparisons). No significant associations were found for comparisons of GCA patients with and those without PMR or GCA patients with and those without ischemic complications. CONCLUSION: Our findings show that the -592 C/A promoter polymorphism of the IL-10 gene is associated with susceptibility to GCA.

Aged↗

PubMed2006

Relationship between interleukin 6 promoter polymorphism at position -174, IL-6 serum levels, and the risk of relapse/recurrence in polymyalgia rheumatica.

OBJECTIVE: To assess the role of -174 G/C promoter polymorphism of interleukin 6 (IL-6) in the susceptibility to polymyalgia rheumatica (PMR). We also investigated whether this polymorphism modulates the circulating level of IL-6 and the risk of relapse/recurrence in a series of patients with PMR followed up prospectively. METHODS: A prospective study of 112 consecutive, untreated patients with isolated PMR (i.e., without evidence of giant cell arteritis) who were followed up for at least 24 months. This cohort represented all patients diagnosed over a 5-year period in one Italian rheumatological secondary referral center. Patients were monitored for clinical signs/symptoms and acute-phase reactants. All PMR patients and 112 population-based controls from the same geographic area were genotyped for IL-6 polymorphism at position -174 by molecular methods. IL-6 serum levels were measured in 67 PMR patients and 43 population-based controls. RESULTS: The distribution of the G/C 174 genotype was similar in PMR patients and controls. No significant associations with IL-6 promoter polymorphism at position -174 were found when PMR patients with and without relapse/recurrence were compared. Controls homozygous for the C allele had higher serum IL-6 levels than the carriers of the G allele (4.5 +/- 3.7 pg/ml vs 1.8 +/- 2.1 pg/ml, p = 0.01). Patients homozygous for the allele C had significantly higher values of IL-6 during followup than patients carrying GC or GG genotypes. CC homozygosity was significantly more frequent in patients with persistently elevated levels of IL-6 than in those without. The presence of persistently elevated IL-6 levels, but not the CC genotype, was associated with an increased frequency of relapse/recurrence. CONCLUSION: Our findings show that the 174 G/C promoter IL-6 polymorphism is not implicated in susceptibility to PMR. However, CC genotype characterized PMR patients with persistently elevated levels of IL-6 who are at higher risk of developing relapse/recurrence. A genetically modulated pattern of IL-6 production could affect the longterm outcome of patients with PMR.

Aged↗

PubMed2006

Tumor necrosis factor-alpha protects synovial cells from nitric oxide induced apoptosis through phosphoinositide 3-kinase Akt signal transduction.

OBJECTIVE: To investigate the anti-apoptotic role of tumor necrosis factor-a (TNF-a) and its signaling pathways in cultured human fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis. METHODS: FLS were cultured in Dulbecco's modified Eagle's medium. Apoptotic cells were identified by TUNEL assay and Hoechst staining. Cell viability was determined by the MTT method. Expression of phospho-Akt and phospho-BAD was measured by Western blotting. RESULTS: A 24-h TNF-a treatment prevented FLS apoptosis induced by nitric oxide (NO) donor sodium nitroprusside dihydrate (SNP), achieving 70% protection. At 1-10 ng x ml-1 concentrations, TNF-a induced phosphorylation of Akt and BAD in a time and concentration-dependent manner. This effect was blocked by treatment with both LY294002 and nuclear factor-kB inhibitor pyrrolidine-dithiocarbamate. CONCLUSION: TNF-a has an anti-apoptotic effect in human FLS. Activation of Akt and BAD may have an important role in this process.

Apoptosis↗

PubMed2005

Positron emission tomography (PET): evaluation of chronic periaortitis.

OBJECTIVE: To evaluate the presence and extent of large-vessel inflammation in patients with chronic periaortitis (CP) using (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET). METHODS: A consecutive case series consisting of 7 patients with CP seen over a 3-year period and a control group of 14 patients with malignancy were evaluated with FDG-PET. For every case we selected 2 age- and sex-matched controls who underwent PET imaging for malignancy. The diagnosis of CP was made by means of computed tomography. PET imaging was performed at diagnosis before therapy was started. Measurement of vascular uptake was graded using a 4-point semiquantitative scale. RESULTS: All patients had evidence of grade 2+ or 3+ vascular uptake in the abdominal aorta and/or iliac artery. No controls showed vascular uptake greater than 1+. Vascular uptake in the thoracic aorta and/or in its branches was seen in 3 (43%) of 7 patients. Vascular uptake in abdominal aorta and/or iliac artery was observed in patients with CP but not in controls (100% versus 0%). There was also a significantly more frequent FDG uptake in the large thoracic arteries in case-patients compared with controls (43% versus 0%; P = 0.03). CONCLUSION: FDG-PET scan shows in patients with CP the presence of a large-vessel vasculitis involving abdominal aorta and common iliac arteries, which in some patients is also extended to thoracic aorta and/or its branches.

Adult↗

PubMed2005

Risk factors for visual loss in an Italian population-based cohort of patients with giant cell arteritis.

OBJECTIVE: To evaluate the frequency of visual manifestations at presentation in an Italian population-based cohort of patients with biopsy-proven giant cell arteritis (GCA), and to investigate predictors for the development of permanent visual loss. METHODS: We identified 136 Reggio Emilia (Italy) residents with biopsy-proven GCA diagnosed between 1986 and 2002. Medical records of these 136 patients were reviewed, and demographic, clinical, and laboratory data were collected.Multivariate analysis with multiple logistic regression models was performed to identify the best predictors of visual loss. RESULTS: Visual manifestations developed in 41 patients (30.1%). Partial or total visual loss was observed in 26 patients (19.1%). Anterior ischemic optic neuropathy was seen in 24 patients, and 2 patients had central retinal artery occlusion. Unilateral vision loss occurred in 19 patients, and bilateral visual loss in 7. In 25 patients, visual loss developed before glucocorticoid therapy for GCA was started. The age at disease onset was significantly higher in patients with permanent visual loss compared with those without it. The frequency of systemic signs/symptoms and erythrocyte sedimentation rate (ESR) and C-reactive protein values at diagnosis were significantly lower in patients with permanent visual loss. By multivariate logistic regression, the only statistically significant predictor for the development of permanent visual loss was the absence of high levels of ESR at diagnosis (tertile 2: Odds ratio [OR] 0.08; tertile 3: OR 0.11). Other predictors included in the model were the absence of systemic manifestations (OR 0.24), an older age at disease diagnosis (quintile 5: OR 5.60), and the presence of an elevated platelet count at diagnosis (OR 4.99), however they were only of borderline statistical significance. CONCLUSION: The proportion of Italian patients with GCA that developed visual loss was similar to that reported from other countries. The patients with low inflammatory response had a higher risk of visual loss.

Age of Onset↗

PubMed2005

Acute-phase reactants and the risk of relapse/recurrence in polymyalgia rheumatica: a prospective followup study.

OBJECTIVE: To determine laboratory parameters that may be useful in identifying polymyalgia rheumatica (PMR) patients who require long-term corticosteroid therapy. METHODS: A prospective followup study of 94 consecutive untreated patients with PMR were assessed for relapse/recurrence for a mean of 39 months. This cohort represented all the patients diagnosed over a 4-year period in 2 Italian secondary referral centers. Patients were monitored for clinical signs and symptoms, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum interleukin-6 (IL-6). IL-6 levels were also measured in 43 controls matched to the patients for age and sex. RESULTS: The ESR was elevated in 91.5% of the patients prior to therapy initiation, as were CRP in 98.9% and serum IL-6 in 92.6%. Forty-seven (50.0%) patients had at least 1 relapse/recurrence during the followup period and 24 (25.5%) had at least 2. After 4 weeks of prednisone therapy, ESR was elevated in 13.2% patients, CRP in 41.9%, and serum IL-6 in 37.2%. IL-6 levels remained persistently elevated in 9.9% and CRP in 8.7% of patients during the first year of followup, whereas no patient had persistently elevated ESR. Persistently elevated CRP and IL-6 levels were significantly associated with an increased risk of relapse/recurrence. In particular, patients with persistently elevated levels of IL-6 during the first year of therapy had the highest relative risk. CONCLUSION: Despite the control of clinical symptoms, corticosteroids do not adequately control the inflammatory process in a subset of patients with PMR who have persistently elevated levels of CRP and IL-6 and who have a higher risk of relapsing.

Acute-Phase Proteins↗

PubMed2005

Are steroids alone sufficient for the treatment of giant cell arteritis?

Glucocorticosteroids are the cornerstone of treatment of giant cell arteritis. An initial dose of prednisone or its equivalent of at least 40-60mg per day as single or divided dose is usually adequate. Glucocorticosteroids may prevent, but usually do not reverse, visual loss. A treatment course of 1-2 years is often required. Some patients, however, have a more chronic-relapsing course and may require low doses of glucocorticosteroids for several years. Glucocorticosteroid-related adverse events are common. In studies on immunosuppressant agents, methotrexate has been used as a glucocorticosteroid-sparing drug with conflicting results. This drug may, however, be given to patients who need high doses of glucocorticosteroids to control active disease and who have serious side effects. A recent pilot study found that infliximab was efficacious in patients with glucocorticosteroid-resistant giant cell arteritis. However, randomized controlled trials are required to define the role of anti-tumor necrosis factor-alpha agents in the treatment of giant cell arteritis. Finally, low-dose aspirin has been shown in a recent retrospective study to decrease the rate of cranial ischemic complications secondary to giant cell arteritis. It is conceivable that the definition of different patterns of inflammation in giant cell arteritis in the future might facilitate the design of differentiated therapeutic approaches.

Clinical Trials as Topic↗

PubMed2005

Interleukin-6 promoter polymorphism at position -174 in giant cell arteritis.

OBJECTIVE: To investigate potential associations between the -174 G/C interleukin-6 (IL-6) promoter polymorphism and susceptibility to and clinical features of giant cell arteritis (GCA), particularly in patients with or without polymyalgia rheumatica (PMR) and with or without ischemic complications. METHODS: One hundred and twenty-six patients with biopsy-proven GCA who were residents in Reggio Emilia, Italy, and 112 population-based controls from the same geographic area were genotyped for IL-6 polymorphism at position -174 by molecular methods. Patients were divided in subgroups according to presence or absence of PMR and ischemic complications (visual loss, jaw claudication, cerebrovascular accidents, aortic arch syndrome). RESULTS: Distribution of the G/C 174 genotype was similar in patients with GCA and controls. No significant associations with the IL-6 promoter polymorphism at position -174 were found when GCA patients with or without PMR or with or without ischemic complications were compared. Further, IL-6 genotypes did not significantly affect levels of C-reactive protein or other inflammatory markers at diagnosis. CONCLUSION: Our findings show that the 174 G/C promoter IL-6 polymorphism does not seem to be implicated in susceptibility to and clinical expression of GCA.

Aged↗

PubMed2004

Factor V Leiden and prothrombin gene G20210A mutations in Italian patients with Behçet's disease and deep vein thrombosis.

OBJECTIVE: To evaluate the frequency and type of vascular lesions and to study the association of factor V gene G1691A (Leiden) and prothrombin gene G20210A polymorphisms with venous thrombosis in Italian patients with Behçet's disease (BD). METHODS: Included were 118 consecutive Italian BD patients followed over a 3-year period (1997-1999) who satisfied the International Study Group criteria for BD. The control group consisted of 132 healthy Italian blood donors. All BD patients and controls were genotyped by polymerase chain reaction and allele-specific restriction enzyme techniques for factor V Leiden and prothrombin gene G20210A polymorphisms. RESULTS: Vascular lesions were observed in 37 (31.4%) patients. The 2 most common lesions were subcutaneous thrombophlebitis (10.2%) and deep vein thrombosis (DVT) of the legs (22.8%). No significant demographic and clinical differences between patients with and without DVT were present. The distribution of allele and genotype frequencies of prothrombin gene G20210A and factor V Leiden polymorphisms did not differ significantly between BD patients and healthy controls. The frequencies of carriage rates of prothrombin gene G20210A and factor V Leiden polymorphisms in BD patients with and without DVT were similar. However, the frequency of 20210A allele was significantly higher in BD patients with ocular disease than in those without, particularly in the patients with posterior uveitis/retinal vasculitis. CONCLUSIONS: The frequency and types of vascular lesions in Italian BD patients were similar to those reported in studies from other countries. No association between factor V Leiden mutation and G20210A mutation in the 3'-untranslated region of the prothrombin gene with DVT was found. However, a prothrombin gene G20210A mutation may influence the development and severity of ocular involvement in BD.

Adolescent↗

PubMed2004

Polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is an inflammatory condition of unknown etiology characterized by aching and stiffness in the shoulder and in the pelvic girdles and neck. In the past, PMR was considered a manifestation of giant cell arteritis (GCA) or a variant of elderly-onset rheumatoid arthritis (EORA). The current diagnostic criteria for PMR were empirically formulated by clinical experts who had studied the disease extensively. Arthroscopic, radioisotopic and magnetic resonance imaging studies all have indicated the presence of a synovitis in proximal joints and periarticular structures. The synovitis is probably responsible for the musculoskeletal symptoms in PMR. The prominence assigned to the proximal symptoms has probably overshadowed the less well recognized and more variable distal musculoskeletal manifestations which are present in about half of the cases. A normal erythrocyte sedimentation rate does not exclude a diagnosis of PMR. C-reactive protein and interleukin-6 seem to be more sensitive indicators of disease activity both at diagnosis and during relapse/recurrence. Corticosteroids are the drugs of choice for treating PMR. A course of treatment of 1-2 years is often required. However, some patients have a chronic, relapsing course and require low doses of corticosteroids for several years. Large, multicenter, double-blind, placebo-controlled studies are required to define the role of methotrexate and anti-TNF-alpha agents as corticosteroid-sparing drugs in PMR.

Aged↗

PubMed2004

Are polymyalgia rheumatica and giant cell arteritis the same disease?

OBJECTIVE: To summarize the evidence about the relationship between polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). METHODS: Review of relevant articles from the English-language literature. RESULTS: Epidemiologic studies suggest that PMR and GCA are closely related conditions affecting people over 50 years and frequently occurring in the same patient. PMR symptoms have been observed in 40 to 60 percent of GCA clinical series. Also, temporal artery biopsy may yield positive results for GCA in patients with isolated PMR. Conflicting HLA-DRB1 genotype results have been reported, and recent studies have shown that PMR and GCA have different expression of RANTES, TNFalpha microsatellite, and IL-6 promoter genetic polymorphisms. Search for a possible common infectious agent have yielded disappointing results. Although parvovirus B19 DNA is present in the artery wall of patients with GCA, this virus may be only an innocent bystander. Cytokine studies on a limited number of temporal artery biopsy specimens have shown that interferon-gamma is produced in GCA and not in PMR, suggesting that this cytokine may be crucial to the development of overt vasculitis. CONCLUSIONS: PMR and GCA frequently occur together but no definitive conclusions can be drawn about the nature of this association.

Aged↗

PubMed2004

Fat suppression magnetic resonance imaging in shoulders of patients with polymyalgia rheumatica.

OBJECTIVE: To evaluate the sites of inflammatory process in the shoulders of patients with polymyalgia rheumatica (PMR) using fat suppressed magnetic resonance imaging (MRI). METHODS: Six consecutive, untreated new patients with PMR were investigated. Five patients with early rheumatoid arthritis (RA) and 4 patients with early psoriatic arthritis (PsA) with bilateral shoulder symptoms served as a control group. Bilateral shoulder fat-suppressed MRI sequences were performed in all patients and controls. We evaluated the presence of joint synovitis, bursitis, tenosynovitis, and bone and soft tissue edema. RESULTS: Bilateral subacromial/subdeltoid bursitis was found in all patients with PMR, in 1/5 (20%) patients with RA (p < 0.05), and in none with PsA (p < 0.02). Glenohumeral synovitis was present in all case and controls. Biceps tenosynovitis was observed in 4/6 (67%) patients with PMR, in 4/5 (80%) with RA (not significant, NS), and in all 4 patients with PsA (NS). No evidence of bone edema adjacent to the joint capsule and entheseal insertions or in the soft tissues was present in either cases or controls. CONCLUSION: The absence of extracapsular abnormalities in the early shoulder disease of PMR does not confirm the hypothesis of a capsular-based disorder.

Aged↗

PubMed2004

Geographical and genetic factors do not account for significant differences in the clinical spectrum of giant cell arteritis in southern europe.

OBJECTIVE: To investigate whether genetic and geographical differences may influence the clinical spectrum of giant cell arteritis (GCA), we compared the demographic and clinical features of patients with biopsy-proven GCA from Reggio Emilia (Northern Italy) and Lugo (Northwest Spain) during a 15-year period. METHODS: We performed a retrospective review of the case records of all patients diagnosed with biopsy-proven GCA at Hospital Xeral-Calde (Lugo, Spain) and Hospital Santa Maria Nuova (Reggio Emilia, Italy) between 1 January 1986 and 31 December 2001. Both hospitals are the only referral centers for populations living in central Galicia and central Emilia Romagna, respectively. RESULTS: During the period of study, 194 Lugo residents and 126 Reggio Emilia residents were diagnosed with biopsy proven GCA. Reggio Emilia patients were more likely to be female (74% vs 54%; p = 0.0001). Although Lugo patients complained of headache (86%) more commonly than did those from Reggio Emilia (77%), the difference was only marginally significant (p = 0.05). The proportion of patients with visual manifestations or visual loss was remarkably similar (22% for visual manifestations and 17% for visual loss in Lugo and 29% and 21% for Reggio Emilia residents). The mean erythrocyte sedimentation rate prior to the onset of therapy was also similar. CONCLUSION: Apart from differences in sex, the clinical spectrum of GCA in these 2 Southern European regions was similar.

Aged↗

PubMed2004

Vascular endothelial growth factor gene polymorphisms in Behçet's disease.

OBJECTIVE: To evaluate potential associations of vascular endothelial growth factor (VEGF) gene polymorphisms with Behçet's disease (BD) and disease expression. METHODS: Case patients were 122 consecutive Italian patients with BD followed at the Rheumatology, Ophthalmology, and Neurology Units in Bologna, Ferrara, Milano, Palermo, Potenza, Prato, Reggio Emilia, and Trento over a 3-year period (1997-99) and who satisfied the International Study Group criteria for BD. Also selected as a control group were 200 healthy age and sex matched blood donors. All patients with BD and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for +936 C/T (rs3025039) and -634 C/G (rs2010963) mutations and for an 18 base pair (bp) insertion/deletion (I/D) polymorphism at -2549 of the the VEGF promoter region. In vitro release of VEGF by peripheral blood mononuclear cells (PBMC) was investigated by ELISA in healthy controls homozygous for the polymorphisms studied. RESULTS: The carriage rates of the alleles I and -634C were significantly more frequent in patients with BD than in healthy controls [p corr = 0.036, OR 1.8 (95% CI 1.1-2.9) and p corr = 0.05, OR 1.8 (95% CI 1.1-3.0), respectively]. While the distribution of allele +936T was similar in patients with BD and healthy controls, its frequency was significantly higher in BD patients with posterior uveitis/retinal vasculitis than in those without (p = 0.022, OR 2.4, 95% CI 1.1-5.0). Lipopolysaccharide-stimulated VEGF production from PBMC of healthy subjects was higher in II homozygous than in DD homozygous. CONCLUSION: Our data indicate that carriers of -634C and I alleles are associated with susceptibility to developing BD.

Adolescent↗

PubMed2003

Efficacy of infliximab in resistant psoriatic arthritis.

OBJECTIVE: To evaluate the efficacy and safety of the anti-tumor necrosis factor alpha monoclonal antibody infliximab in the treatment of active psoriatic arthritis (PsA) resistant to previous symptom modifying antirheumatic drugs. METHODS: Sixteen patients with peripheral active PsA with at least 6 months of methotrexate (MTX) therapy at a stable dosage were treated with infliximab administered at a dosage of 3 mg/kg at 0, 2, 6, 14, 22, and 30 weeks while continuing to receive MTX. Intake of nonsteroidal antiinflammatory drugs and corticosteroids was stable during the study period. Standard clinical assessments, erythrocyte sedimentation rate (ESR), and C reactive protein (CRP) were determined at baseline and at weeks 2, 6, 14, 22, and 30. RESULTS: By week 2, significant improvements were registered in the number of swollen and tender joints, visual analog scale for pain, patient and doctor global disease assessment scores, Health Assessment Questionnaire, Dougados functional index, ESR, and CRP. At week 30, the percentages of patients satisfying American College of Rheumatology (ACR) 20%, ACR 50%, and ACR 70% response rates were 64%, 57%, and 57%, respectively. In the 3 patients with active axial disease, spinal stiffness and pain resolved almost completely at week 2 and the improvement did not diminish over time. Psoriasis Area Severity Index improvement was 37% at week 2 and 86% at week 30. No patients dropped out for treatment failure. Side effects were observed in 4 of 16 patients, 2 of whom suspended the therapy due to a severe allergic reaction. CONCLUSION: In patients with resistant PsA, infliximab is an effective therapy without major side effects.

Adult↗

PubMed2003

Endothelial nitric oxide synthase gene polymorphisms in giant cell arteritis.

OBJECTIVE: To examine potential associations of the Glu/Asp(298) polymorphism in exon 7 and the 4a/b polymorphism in intron 4 of the endothelial nitric oxide synthase (eNOS) gene with susceptibility to and clinical expression of giant cell arteritis (GCA), particularly in patients with versus those without ischemic complications. METHODS: Ninety-one consecutive patients with biopsy-proven GCA, who were residents of Reggio Emilia, Italy, and 133 population-based controls from the same geographic area were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for eNOS polymorphisms in exon 7 and intron 4. The patients were separated into 2 subgroups according to the presence or absence of ischemic complications (visual loss and/or jaw claudication and/or aortic arch syndrome). RESULTS: The distribution of the Glu/Asp(298) genotype differed significantly between GCA patients and controls (corrected P [P(corr)] = 0.003). Carriers of the Asp(298) allele (Asp/Asp or Glu/Asp) were significantly more frequent among the GCA patients than among the controls (P(corr) = 0.0002, odds ratio 3.3, 95% confidence interval 1.7-6.3). The distribution of the 4a/b genotype was similar in GCA patients and controls. No significant associations were found when GCA patients with and without ischemic complications were compared. CONCLUSION: Our findings show that the Glu/Asp(298) polymorphism of the eNOS gene is associated with GCA susceptibility.

Aged↗

PubMed2003

Treatment of refractory polymyalgia rheumatica with infliximab: a pilot study.

OBJECTIVE: To investigate whether infliximab has a steroid-sparing effect in the treatment of patients with polymyalgia rheumatica (PMR) who are resistant to corticosteroid (CS) therapy and have had CS-related side effects. METHODS: In a pilot study, infliximab 3 mg/kg was administered at weeks 0, 2, and 6 in 4 patients with relapsing PMR who were not able to reduce their prednisone dose below 7.5-12.5 mg/day and who had experienced multiple vertebral fractures. The patients were regularly monitored for clinical signs/symptoms and erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and interleukin-6 (IL-6) during the one-year followup period. RESULTS: Two patients had a complete response to infliximab with clinical remission 2 weeks after the first infusion. At this time ESR and IL-6 values were normal and the patients were able to suspend prednisone. Normal ESR, CRP, and IL-6 levels persisted after the suspension of infliximab and prednisone during the followup period, paralleling the clinical remission. The third patient had a complete and persistent clinical remission 2 weeks after the first infusion, although IL-6 levels remained elevated during the followup period despite the normalization of ESR values. These 3 patients were symptom-free with normal ESR and CRP at the end of 1-year of followup. The fourth patient had continuous clinical activity associated with persistently elevated acute phase reactants, although IL-6 levels measured during followup were lower compared to baseline values and the patient was able to reduce prednisone dosage to 5 mg/day. CONCLUSION: Our encouraging results suggest that a controlled study may assess the efficacy of infliximab as CS-sparing drug in PMR.

Antibodies, Monoclonal↗

PubMed2003

Vascular endothelial growth factor gene polymorphisms in giant cell arteritis.

OBJECTIVE: To examine potential associations of vascular endothelial growth factor (VEGF) gene polymorphisms with giant cell arteritis (GCA) and disease expression, in particular in patients with and without ischemic complications. METHODS: We enrolled 92 consecutive patients with biopsy-proven GCA residing in Reggio Emilia, Italy. Two hundred healthy blood donors from the same geographic area were selected as controls. All the GCA patients and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for 936 C/T and 634 C/G mutations and for an 18 bp insertion/deletion (I/D) polymorphism in the VEGF promoter region. In vitro release of VEGF by peripheral blood mononuclear cells (PBMC) was investigated by ELISA in controls homozygous for the polymorphisms studied. RESULTS: The carriage rates of the alleles I and C634 were significantly more frequent in GCA patients than in controls (p = 0.025, OR 1.9, 95% CI 1.1-3.1 and p = 0.015, OR 2.1, 95% CI 1.1-3.6, respectively). The distribution of allele T936 was similar in GCA patients and controls. No significant differences in the distribution of the polymorphisms studied were observed in patients with ischemic manifestations compared to those without ischemic manifestations. Lipopolysaccharide (LPS)-stimulated VEGF production by PBMC from controls was higher in II homozygous compared to DD homozygous patients. CONCLUSION: Our data indicate that carriers of C634 and I alleles are associated with susceptibility to developing GCA.

Aged↗