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J Font

Publications and source records attributed to J Font.

At least 55 records · Page 3Linked to original sources

Usefulness of basal and pilocarpine-stimulated salivary flow in primary Sjögren's syndrome. Correlation with clinical, immunological and histological features.

OBJECTIVES: To examine salivary function in patients with primary Sjögren's syndrome (SS) by assessing unstimulated and stimulated flows using 5 mg of pilocarpine in a 5% solution, in order to define their clinical usefulness in the evaluation of xerostomia in patients with primary SS as well as to identify those factors related to the increase in salivary flow after pilocarpine stimulation. METHODS: We investigated the clinical and immunological characteristics of 60 consecutive patients with primary SS. All patients fulfilled four or more of the preliminary diagnostic European criteria for SS. We measured unstimulated (basal) salivary flow (BSF) in all patients. In patients with BSF </=1.5 ml, stimulated salivary flows (SSF) were also measured after stimulation with an ophthalmic 5% pilocarpine solution (0.1 ml=5 mg, administered sublingually). SSF was also measured after oral administration of 50 mg anetholetrithione (ANTT) in the same patients. These stimulated salivary flows were measured 1, 2 and 3 h after the stimulus. RESULTS: Of the 60 patients, 55 were women and five men, with a mean age at the SS onset of 61 yr (range 18-82 yr). The mean BSF for SS patients was 1.40+/-0.17 ml. Fifty (83%) patients showed a BSF less than 1.5 ml. The stimulated salivary flow after 1 h was 3.23 ml in the pilocarpine group and 0.57 in the ANTT group (P<0.001); after 2 h it was 1.32 ml in the pilocarpine group and 0.52 in the ANTT group (P=0.02) and after 3 h it was 0.80 ml in the pilocarpine group and 0.41 in the ANTT group (P=0.046). No clinical or immunological differences were found between SS patients with BSF more or less than 1.5 ml, although patients with a BSF less than 1.5 ml showed a parotid scintigraphy class III or IV more frequently (42 vs 0%, P=0.01). SS patients with a pilocarpine SSF less than 1.5 ml had a longer duration of SS (73.3 vs 31.3 months, P=0.03) and a higher prevalence of positive anti-Ro/SS-A (70 vs 36%, P=0.038), anti-La/SS-B (65 vs 32%, P=0.038), parotid scintigraphy class III-IV (79 vs 9%, P<0.001) and positive salivary gland biopsy (90 vs 43%, P<0.001). CONCLUSION: The study of xerostomia using basal and pilocarpine SSF is simple to perform, acceptable to patients and needs no special equipment. We describe a significant increase in SSF using a solution of 5% pilocarpine in comparison with salivary flow obtained after stimulation with ANTT. Twenty-two of the 46 patients with low BSF had stimulated flows over 1.5 ml. These 'responder' patients showed a shorter duration of sicca symptoms, a lower frequency of positive immunological markers and milder grades of scintigraphic patterns and lymphocytic infiltrates in salivary gland biopsies. This subset of patients probably maintain a residual capacity of their salivary glands, as opposed to the 'non-responder' patients, who had a longer duration of sicca syndrome evolution with more severe involvement of the salivary glands.

Adolescent↗

The role of interleukin-10 promoter polymorphisms in the clinical expression of primary Sjögren's syndrome.

OBJECTIVE: To analyse the role of polymorphisms of the interleukin-10 promoter region in the epidemiologic, clinical and immunologic characteristics of patients with primary Sjögren's syndrome (SS). METHODS: Sixty-three consecutive patients (59 women and four men; mean age 57 yr; range 20-83 yr) were studied in our Unit. All patients fulfilled four or more of the modified diagnostic criteria for SS proposed by the European Community Study Group in 1996. As controls, 150 healthy volunteers were recruited from the medical and laboratory staff working in our hospital. All the samples from patients and controls were analysed by PCR amplification and direct sequencing. RESULTS: The frequency of the interleukin-10 (IL-10) GCC haplotype was higher (0.48 vs 0.34, P=0.006) and the frequency of the IL-10 ACC haplotype lower (0.25 vs 0.39, P=0.005) in patients with primary SS compared with healthy controls. In the genotype analysis, the frequency of the GCC/ATA genotype was higher (29 vs 11%, P=0.001) and that of the ACC/ACC genotype lower (3 vs 12%, P=0.044) in patients with primary SS compared with healthy controls. GCC-carriers showed an earlier onset of the disease (48.06+/-14.98 yr vs 57.53+/-14.20 yr, P=0.034). The existence of systemic involvement (defined by cutaneous vasculitis, peripheral neuropathy, renal and/or pulmonary involvement) was more frequent in carriers of the GCC haplotype, although the difference did not reach statistical significance (40 vs 27%, P=0.278). No significant differences in the haematologic (hypergammaglobulinaemia, elevated ESR) and immunologic (ANA, RF, anti-Ro/SS-A and anti-La/SS-B antibodies) parameters were observed in carriers of the GCC haplotype. CONCLUSION: We describe an abnormal distribution of IL-10 promoter haplotypes in patients with primary SS compared with healthy controls. This consists of a predominance of the GCC haplotype, mainly related to a higher frequency of the heterozygote haplotype GCC/ATA. The presence of the GCC haplotype does not originate a different immunologic pattern but leads to an earlier onset of primary SS.

Adult↗

The lung in the antiphospholipid syndrome.

Patients with antiphospholipid syndrome (APS) may develop a broad spectrum of pulmonary disease. Pulmonary thromboembolism and pulmonary hypertension are the most common complications, but microvascular pulmonary thrombosis, pulmonary capillaritis, and alveolar haemorrhage have also been reported. Clinicians should seriously consider these types of vascular injury when evaluating patients with APS who present with dyspnoea, fever, and infiltrates on chest radiography.

Antiphospholipid Syndrome↗

Helicobacter pylori does not play a part in the dyspeptic complaints of rheumatology patients receiving long term treatment with non-steroidal anti-inflammatory drugs.

BACKGROUND: The presence of dyspeptic symptoms is a common finding in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs). Some studies seem to support the involvement of Helicobacter pylori infection in the dyspeptic symptoms reported by these patients, and suggest that eradication may be useful. OBJECTIVE: To determine the variables related to dyspepsia in rheumatology patients requiring NSAID treatment, assessing in particular the role of Helicobacter pylori infection. METHODS: One hundred and eighty six consecutive patients with a rheumatological disorder requiring NSAID treatment (68 male, 118 female; mean (SD) age 55 (15) years) were included in a cross sectional study; dyspeptic symptoms were measured by a previously validated scale. Helicobacter pylori infection was determined by serology. Variables related to the severity of symptoms and the need for antisecretory drugs were determined by multivariate analysis. RESULTS: No relation was found between Helicobacter pylori infection and dyspepsia or any of its surrogate markers (antisecretory drug use or NSAID intolerance). Female sex and treatment with antisecretory drugs were found to be independent predictors for the appearance and severity of dyspeptic symptoms. The only independent predictive variables of the requirement for antisecretory drugs were age, previous ulcer disease, taking NSAIDs with a medium or high anti-inflammatory potential, and the symptoms score. CONCLUSION: Helicobacter pylori infection does not seem to play any part in the gastric symptoms of patients treated long term with NSAIDs.

Anti-Inflammatory Agents, Non-Steroidal↗

Clinical significance of acquired activated protein C resistance in patients with systemic lupus erythematosus.

Antiphospholipid antibodies (aPL) may induce acquired activated protein C resistance (acquired APCR). The role of acquired APCR in patients with systemic lupus erythematosus (SLE) is not well known. To evaluate the prevalence of acquired APCR and its association with clinical manifestations we studied 103 consecutive SLE patients and 103 matched controls. APCR in the undiluted test and after dilution in factor V deficient plasma, factor V Leiden, protein C and S, lupus anticoagulant, and anti-cardiolipin, anti-beta2-glycoprotein I and anti-prothrombin antibodies were determined. Factor V Leiden was found in 4% in both patients and controls. The prevalence of acquired APCR was 22% for the undiluted assay and 17% in the diluted test. In SLE patients, acquired APCR was associated with aPL (39 vs 13% in undiluted assay, P = 0.007; and 33 vs 7% in the diluted test, P = 0.001). Arterial thromboses were found in 24% of patients with acquired APCR and in 6% of patients without (P = 0.04). However, no relationship was found with venous thrombosis. Acquired APCR was also associated with pregnancy losses: miscarriages in 70% of women with acquired APCR vs 32% in those without (P=0.03). Thus, in SLE patients acquired APCR seems to be associated with increased prevalence of arterial thrombosis and pregnancy losses.

Abortion, Spontaneous↗

Lessons from the "Euro-Lupus Cohort".

The "Euro-Lupus Cohort" is composed by 1,000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium - the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

Adolescent↗

Annexin expressions are temporally and spatially regulated during rat hepatocyte differentiation.

Annexin (Anx) 1, 2, 5, and 6 expressions were determined at the transcriptional and translational levels in the rat hepatocytes from gestational day 15 to postnatal day 17. Dramatic shifts were observed in Anx 1 and 2 levels, which peaked at day 1 and gestational day 20, respectively, and reached low levels thereafter. However, Anx 5 and 6 rates were more constant. Prenatal administration of dexamethasone (dex) resulted in a decrease of Anx 1 mRNA levels, and a strong increase in Anx 2 mRNA contents. In adult hepatocytes cultured in the presence of EGF or HGF, Anx 1 and 2 expressions resumed. By immunohistochemistry, Anx 1 was detected only in the cytoplasm of hepatocytes of 1- to 3-day-old rats, Anx 2 and 6 both exhibited a redistribution from the cytoplasm toward the plasma membrane, and Anx 5 was present in the nucleus, cytoplasm, and plasma membrane. Thus, Anx 1, 2, 5, and 6 have individual modes of expression and localization in the differentiating hepatocytes, where they might play unique roles at well defined phases of liver ontogeny.

Animals↗

Activity of proximal promoter of the human beta(1)-integrin gene was increased in Sézary syndrome.

Changes in beta1-integrin expression have been involved in abnormal cellular interactions between malignant lymphocytes from Sézary (Sz) patients and keratinocytes. In this paper, we compare the activity of both distal and proximal promoters of the beta1-integrin gene in malignant lymphocytes from Sz patients with human normal lymphocytes. Activity of both beta1-integrin promoters was also analysed in human normal keratinocytes. Northern blot analysis shows that beta1-integrin mRNA expression is higher in malignant Sz lymphocytes than in normal lymphocytes. CAT assays show that the activity of proximal beta1-integrin promoter is markedly increased (up to 6-fold) in malignant lymphocytes from Sz patients, in comparison to normal lymphocytes. These results suggest that changes in activity of the proximal promoter of beta1-integrin subunit could be, in part, responsible for the abnormal cellular interactions between malignant lymphocytes and keratinocytes observed in Sz syndrome.

Cells, Cultured↗

[Intracardial thrombosis and primary antiphospholipid syndrome. A familial case report].

The main clinical manifestation of antiphospholipid syndrome is repeated thrombotic events in young patients without cardiovascular risk factors. There are several clinical features but the most frequent ones are repeated fetal losses and acute cerebral ischemic events. Cardiac involvement is less frequent. We present a family case with intracardiac thrombosis and secondary cerebral embolism.

Adult↗

Risk factors associated with fetal losses in treated antiphospholipid syndrome pregnancies: a multivariate analysis.

PROBLEM: Pregnancies in women with antiphospholipid syndrome (APS) are associated with obstetric complications despite treatment. The present study analyzes risk factors and evaluates fetal outcome in a large sample of treated APS pregnancies. METHOD OF STUDY: Seventy-seven pregnancies in 56 women were included. Twelve selected variables potentially related to the outcome of treated pregnancies were analyzed in a multivariate logistic regression model. RESULTS: Treated women delivered 65 live infants at 24-41 weeks gestation (mean 36.7+/-0.5) but two neonatal deaths occurred. There were seven first-trimester miscarriages (9%) and five intrauterine fetal demises (6.5%). Thus, the probability of having a live baby under treatment was 82% (95% CI 71.3-89.6%), a figure significantly greater (P <0.001) than that observed before therapy (25.7%; 95% CI 18.7-33.7%). Variables related with fetal outcome in the multivariate model were: preconceptional use of aspirin and abnormal umbilical artery Doppler velocimetry at 23-26 weeks gestation. CONCLUSIONS: The present report shows that in treated APS pregnancies: i) aspirin treatment started preconceptionally is an independent and significant prognostic factor associated with favorable fetal outcome; and ii) abnormal velocity waveforms in the umbilical artery predict adverse outcome of pregnancy.

Abortion, Spontaneous↗

Cryoglobulinemia in systemic lupus erythematosus: prevalence and clinical characteristics in a series of 122 patients.

OBJECTIVES: To determine the prevalence and nature of cryoglobulins in 122 patients with systemic lupus erythematosus (SLE) and identify the clinical and immunologic features related to their presence. METHODS: In a cross-sectional study, we investigated 122 consecutive patients (106 women and 16 men) with SLE who fulfilled the 1982 revised criteria of the American College of Rheumatology for the classification of SLE. All patients had documented medical histories and underwent a medical interview as well as a routine general physical examination by a qualified internist, and their clinical and serologic characteristics were collected on a protocol form. Serum samples were obtained at 37 degrees C, and cryoglobulinemia was estimated by centrifugation at 4 degrees C after incubation for 7 days in all patients. The type of cryoglobulinemia was identified by agarose gel electrophoresis and immunofixation. RESULTS: Cryoglobulins were detected in the sera of 31 SLE patients (25%): 20 patients (65%) had a cryocrit lower than 1%, 8 (26%) had percentages ranging between 1% and 5%, and only 3 patients (9%) had a cryocrit over 5%. Only cutaneous vasculitis (39% v 16%; P = .01) was more prevalent in patients with than in those without cryoglobulins. Rheumatoid factor (RF) (42% v 15%; P = .002) and low CH50 levels (84% v 49%; P <.001) were more prevalent in SLE patients with cryoglobulins. Hepatitis C virus (HCV) infection was investigated in 24 of the 31 cryoglobulinemic SLE patients and was detected in 5 (21%). In comparison, 4 (5%) of the 75 noncryoglobulinemic SLE patients studied were positive (P = 0.035; odds ratio, 4.67). Patients with a cryocrit greater than 1% showed a higher frequency of HCV infection than those with a cryocrit less than or equal to 1% (46% v 0%, P = .01). CONCLUSIONS: Cutaneous vasculitis, RF, hypocomplementemia, and HCV infection were associated with cryoglobulins in SLE patients. Testing for HCV infection is therefore recommended for patients with SLE and cryoglobulinemia to identify this subset of patients for prognostic and therapeutic reasons.

Adolescent↗

Antiphospholipid antibodies and thrombophilic factors in giant cell arteritis.

OBJECTIVES: To evaluate the prevalence of thrombophilic risk factors known to induce intravascular clotting and to assess their relationship with ischemic manifestations in giant cell arteritis (GCA). METHODS: Eighty consecutive patients with established GCA were included: 36 with isolated temporal arteritis (TA), 14 with isolated polymyalgia rheumatica (PMR), and 30 with TA and PMR. Forty-four patients (67%) had ischemic phenomena due to GCA. Twelve patients (15%) had thrombotic events unrelated to GCA (6 strokes, 5 deep venous thrombosis, and 1 myocardial infarction). A control group of 100 age- and sex-matched individuals without autoimmune disease, bleeding disorders, thrombosis, or clinical picture of TA or PMR also was analyzed. All participants were tested for the antiphospholipid antibody (aPL) profile, protein C, protein S, antithrombin activity, factor V Leiden mutation, and prothrombin gene G20210A mutation. We also studied fibrinolysis parameters: plasminogen, tissue-type plasminogen activator (t-PA) antigen, t-PA activity, type-1 plasminogen activator inhibitor (PAI-1) antigen, PAI-1 activity, and the 4G/5G polymorphism of the promoter region of the PAI-1 gene. RESULTS: Eleven patients (18%) tested positive for lupus anticoagulant, 24 (30%) for anticardiolipin antibodies, 9 (11%) for anti-beta 2-glycoprotein I antibodies, and 29 (36%) for antiprothrombin antibodies. No relationship was found between these autoantibodies and ischemic manifestations. None of the patients had decreased protein C, protein S or antithrombin activity. Two patients and 2 controls were heterozygous for factor V Leiden, and only 1 patient and 2 controls were heterozygous for the prothrombin gene G20210A mutation. No statistically significant correlation was found between any thrombophilic factor and GCA-related or GCA-unrelated ischemic events. CONCLUSION: GCA patients have a high prevalence of aPL that is not related to ischemic manifestations. Moreover, GCA-related or GCA-unrelated ischemic manifestations do not appear to be due to congenital thrombophilic risk factors. Semin Arthritis Rheum 31:12-20.

Aged↗

Circulating soluble adhesion molecules in ANCA-associated vasculitis.

BACKGROUND: To evaluate whether changes in concentrations of soluble (s) E-selectin, sP-selectin, sL-selectin, intercellular adhesion molecule 1 (sICAM-1), and vascular cell adhesion molecule 1 (sVCAM-1) reflect disease activity in patients with ANCA-associated vasculitis and whether serum levels of these adhesion molecules are related to the degree of renal failure in patients with chronic renal failure (CRF). SUBJECTS AND METHODS: A sandwich ELISA was used to measure these soluble adhesion molecules in (i) sera from 20 patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (10 patients with Wegener's granulomatosis (WG) and 10 patients with microscopic polyangiitis (MPA)), obtained at the time of diagnosis and during the remission period; (ii) sera from 40 patients with CRF not undergoing haemodialysis. RESULTS: At the time of diagnosis, serum levels of sE-selectin, sICAM-1 and sVCAM-1 (88+/-42 ng/ml, 437+/-184 ng/ml, 1720+/-1174 ng/ml respectively) were significantly higher in patients with ANCA-associated vasculitis than in healthy controls (P<0.0001, P=0.002 and P=0.001 respectively). Serum sP-selectin values did not differ from those obtained in normal donors. In contrast, sL-selectin levels (940+/-349 ng/ml) were significantly lower in patients than those recorded in healthy controls (P<0.0001). A significant decrease in concentrations of sE-selectin, sP-selectin, sICAM-1, and sVCAM-1 was observed between active and remission phases (P<0.0001, P=0.002, P=0.001 and P=0.001 respectively). No significant differences were observed in sL-selectin levels between active and remission phases. sL-selectin concentrations (802+/-306 ng/ml) during the remission phase remained lower than those observed in healthy controls (P<0.0001). No correlation was observed between serum creatinine and sE-selectin, sP-selectin, sICAM-1 and sVCAM-1 in patients of the CRF group. A slight negative correlation was established between creatinine and sL-selectin concentration. CONCLUSIONS: Increased serum levels of sE-selectin, sICAM-1, and sVCAM-1 and decreased levels of sL-selectin in active ANCA-associated vasculitis, and the normalization of sE-selectin, sICAM-1, and sVCAM-1 during the remission phase suggest that the concentration of soluble levels of these adhesion molecules reflects disease activity. The decrease in sP-selectin levels between active and inactive phases also suggest that this receptor may reflect clinical activity. The lack of correlation between serum levels of sE-selectin, sP-selectin, sICAM-1, and sVCAM-1 and the degree of renal failure in patients with CRF suggests that the mechanism of clearance of these molecules is not renal.

Adult↗

Cardiovascular risk factors and the long-term outcome of lupus nephritis.

We evaluated cardiovascular risk factors, morbidity and mortality in patients with lupus nephritis (LN). We prospectively studied 70 consecutive patients with LN, and 70 age- and sex-matched controls with systemic lupus erythematosus (SLE) but no evidence of nephropathy, from 1988 to 1998. Patients were evaluated at entry for hypertension, diabetes, hyperlipidaemia, smoking, menopause and antiphospholipid syndrome. The LN patients (64 women, 6 men) had a mean age of 35 years (SE 1.7, range 11-67). During the 10 years, 15 (21%) LN patients and 18 (25%) of the controls were lost to follow-up. Compared with controls, LN patients had a higher prevalence of hyperlipidaemia (44% vs. 2%, p<0.001), hypertension (44% vs. 9%, p<0.001) and antiphospholipid antibodies (45% vs. 22%, p=0.01) at study onset. At the last visit, 37 (67%) LN patients had normal plasma creatinine, 13 (24%) had renal failure and only five (9%) end-stage renal failure. Hyperlipidaemia (78% vs. 27%, p<0.001) and hypertension (67% vs. 32%, p=0.01) at study onset were associated with development of renal failure. Nine LN patients and one control died (16% vs. 2%, p=0.02). These patients showed more antiphospholipid syndrome (56% vs. 17%, p=0.03) and hyperlipidaemia (78% vs. 37%, p=0.03) at study onset. The main causes of death in LN patients were vascular complications (cardiovascular or cerebrovascular events) in five patients (four of whom had antiphospholipid antibodies) and sepsis in three.

Adolescent↗

High circulating levels of soluble scavenger receptors (sCD5 and sCD6) in patients with primary Sjögren's syndrome.

OBJECTIVE: To determine the existence of circulating levels of soluble scavenger receptors (sCD5 and sCD6) in patients with primary Sjögren's syndrome (SS), and to analyse the correlation with clinical and immunological features of SS. METHODS: Ninety consecutive patients with primary SS were studied. All patients fulfilled four or more of the European diagnostic criteria for SS. sCD5 and sCD6 levels were determined using a specific enzyme-linked immunosorbent assay (ELISA) developed in our laboratory. RESULTS: Detectable levels of sCD5 were found in 39 (43%) SS patients. The mean+/-standard error values of sCD5 were 3.5+/-0.5 ng/ml for patients with SS and 1.9+/-0.1 ng/ml for healthy blood donors (P<0.001). We found higher levels of sCD5 in patients with hypocomplementaemia (6.5 vs 3.5 ng/ml, P=0.03) and cryoglobulinaemia (6.9 vs 2.6 ng/ml, P=0.001). On the other hand, detectable levels of sCD6 were found in 60 (67%) SS patients. The mean+/-standard error values of sCD6 were 25.5+/-7.8 ng/ml in SS patients and 5.27+/-1.40 ng/ml in healthy blood donors (P=0.01). When the sCD6 levels were compared according to the presence or absence of immunological features, patients with cryoglobulinaemia showed higher levels of circulating sCD6 (77.3 vs 17 ng/ml, P=0.01) than those without cryoglobulinaemia. CONCLUSION: Patients with primary SS showed higher levels of circulating sCD5 and sCD6 when compared with controls. Moreover, the existence of some immunological features (hypocomplementaemia and cryoglobulinaemia) was associated with high levels of both soluble scavenger receptors. These facts may reflect an enhanced lymphocytic activation in patients with primary SS.

Adult↗