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J Font

Publications and source records attributed to J Font.

At least 19 recordsLinked to original sources
PubMed2007

Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus: an international inception cohort study.

OBJECTIVE: To describe the prevalence, characteristics, attribution, and clinical significance of neuropsychiatric (NP) events in an international inception cohort of systemic lupus erythematosus (SLE) patients. METHODS: The study was conducted by the Systemic Lupus International Collaborating Clinics (SLICC). Patients were enrolled within 15 months of fulfilling the American College of Rheumatology (ACR) SLE classification criteria. All NP events within a predefined enrollment window were identified using the ACR case definitions of 19 NP syndromes. Decision rules were derived to determine the proportion of NP disease attributable to SLE. Clinical significance was determined using the Short Form 36 (SF-36) Health Survey and the SLICC/ACR Damage Index (SDI). RESULTS: A total of 572 patients (88% female) were recruited, with a mean +/- SD age of 35 +/- 14 years. The mean +/- SD disease duration was 5.2 +/- 4.2 months. Within the enrollment window, 158 of 572 patients (28%) had at least 1 NP event. In total, there were 242 NP events that encompassed 15 of 19 NP syndromes. The proportion of NP events attributed to SLE varied from 19% to 38% using alternate attribution models and occurred in 6.1-11.7% of patients. Those with NP events, regardless of attribution, had lower scores on the SF-36 and higher SDI scores compared with patients with no NP events. CONCLUSION: Twenty-eight percent of SLE patients experienced at least 1 NP event around the time of diagnosis of SLE, of which only a minority were attributed to SLE. Regardless of attribution, the occurrence of NP events was associated with reduced quality of life and increased organ damage.

Adult↗
PubMed2006

The catastrophic antiphospholipid (Asherson's) syndrome and malignancies.

The catastrophic antiphospholipid syndrome is characterised by the rapid chronological development of fulminant thrombotic complications that predominantly affect small vessels. It has been reported as frequently occurring in patients with underlying malignancies. We analysed the web site-based international registry of patients with catastrophic APS. The clinical characteristics of patients with CAPS and an underlying malignancy were evaluated. Of the 262 patients included in the CAPS registry, information on associated malignancies was available in 23 (9%) cases. Haematological malignancies were present in 6 (26%) patients. Four of the patients suffered from lung carcinoma (17%), and two patients (9%) from colon carcinoma. In most of the patients (61%), malignancy was the precipitating factor for CAPS. In 4 patients (17%), however, surgical procedures related to the carcinoma were noted as precipitating factors. In one patient CAPS occurred during allogenic stem cell transplantation after diagnosis of acute lymphoblastic leukemia (ALL). Cerebral manifestations were most common and consisted mainly of cerebral infarcts and encephalopathy. Recovery occurred in 9/23 (39%) patients. Malignancy may be an important risk factor for CAPS. 9% of patients with CAPS presented with an underlying malignancy. In most of these patients, the malignancy and/or surgical procedures were the precipitating factors for CAPS.

Adolescent↗
PubMed2006

Association of mannose-binding lectin gene polymorphisms with antiphospholipid syndrome, cardiovascular disease and chronic damage in patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the association of mannose-binding lectin (MBL)-deficient genotypes with cardiovascular disease in a large series of patients with systemic lupus erythematosus (SLE). METHODS: A total of 114 patients diagnosed with SLE were included in the study. MBL polymorphisms were investigated by sequencing-based DNA typing of the promoter and exon 1 of the MBL2 gene. The genotypes 0/0, 0/XA and XA/XA were considered as MBL-low genotypes. RESULTS: A higher prevalence of cardiovascular disease was observed in patients carrying MBL-low genotypes compared with those carrying MBL-high genotypes [30 vs 9%, P = 0.012, odds ratio (OR) 4.54, 95% confidence interval (CI) 1.20-16.46]. Patients with MBL-low genotypes also presented higher mean values for total cholesterol (228.6 vs 202.3 mg/dl, P = 0.017) and low-density lipoprotein (LDL) cholesterol (139.9 vs 121.9 mg/dl, P = 0.045), a higher frequency of chronic renal failure (30 vs 4%, P = 0.001), vasculitis (30 vs 11%, P = 0.043), heart valve lesions (71 vs 32%, P = 0.026), cardiac valve dysfunction (57 vs 7%, P = 0.0004) and associated APS (39 vs 12%, P = 0.005), a higher mean Systemic Lupus International Collaborating Clinics score (2.09 vs 1.26, P = 0.029) and a lower prevalence of low C4 levels (43 vs 71%, P = 0.015). Multivariate analysis of genetic, clinical and immunological variables showed that only antiphospholipid syndrome (APS) was independently associated with cardiovascular events (P = 0.001). CONCLUSION: Although the prevalence of cardiovascular disease in our SLE patients carrying MBL-deficient genotypes was 3.3 times higher than in patients with non-deficient genotypes, only APS was independently associated with cardiovascular events. This suggests that the higher frequency of thrombotic events in SLE patients carrying MBL-deficient genotypes might be related to coexisting APS.

Adolescent↗
PubMed2006

Pressure-jump-induced kinetics reveals a hydration dependent folding/unfolding mechanism of ribonuclease A.

Pressure-jump (p-jump)-induced relaxation kinetics was used to explore the energy landscape of protein folding/unfolding of Y115W, a fluorescent variant of ribonuclease A. Pressure-jumps of 40 MPa amplitude (5 ms dead-time) were conducted both to higher (unfolding) and to lower (folding) pressure, in the range from 100 to 500 MPa, between 30 and 50 degrees C. Significant deviations from the expected symmetrical protein relaxation kinetics were observed. Whereas downward p-jumps resulted always in single exponential kinetics, the kinetics induced by upward p-jumps were biphasic in the low pressure range and monophasic at higher pressures. The relative amplitude of the slow phase decreased as a function of both pressure and temperature. At 50 degrees C, only the fast phase remained. These results can be interpreted within the framework of a two-dimensional energy surface containing a pressure- and temperature-dependent barrier between two unfolded states differing in the isomeric state of the Asn-113-Pro-114 bond. Analysis of the activation volume of the fast kinetic phase revealed a temperature-dependent shift of the unfolding transition state to a larger volume. The observed compensation of this effect by glycerol offers an explanation for its protein stabilizing effect.

Animals↗
PubMed2006

Infections in systemic lupus erythematosus: a prospective and controlled study of 110 patients.

We decided to analyse the incidence and characteristics of infection in systemic lupus erythematosus (SLE) and determine the related risks factors. One-hundred and ten SLE patients and 220 controls were prospectively followed up over three years and all the infectious episodes were recorded. A case-control design was established to identify risk factors of infection. Thirty-nine SLE patients suffered at least one infection (36%) versus 53 controls (22%), RR = 1.63 (P < 0.05). The incidence of urinary infections, pneumonia and bacteraemia without known focus was significantly greater in SLE. E. coli was the chief isolated microorganism (21.3%). In the univariate analysis, nephritis, SLE activity, leucopenia, anti-dsDNA levels above 20 IU/mL, CH50 levels under 300 IU/mL, ever use of steroids, daily dose of prednisone higher than 10 mg and ever use of cyclophosphamide were significantly associated with infection. In the multivariate analysis, total serum complement levels below 300 UU/mL and a daily dose of prednisone above 20 mg during at least one month plus ever use of cyclophosphamide were found to be significant (P < 0.0001). We conclude that patients with SLE have an increased overall risk for infection and they are especially prone to develop urinary infection, pneumonia and bacteraemia without focus. Hypocomplementaemia represents an independent predictive factor for infection. It seems mandatory to closely follow up SLE patients with low complement levels and instruct them to report any suspicious sign of infection, especially in those receiving more than 20 mg/day of prednisone who have also been administered cyclophosphamide.

Adolescent↗
PubMed2005

Systemic lupus erythematosus in Europe at the change of the millennium: lessons from the "Euro-Lupus Project".

The "Euro-Lupus Cohort" is composed by 1000 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.

Age of Onset↗
PubMed2005

Validation of the preliminary criteria for the classification of catastrophic antiphospholipid syndrome.

OBJECTIVE: To describe the characteristics of patients with catastrophic antiphospholipid syndrome (APS) included in the International Registry of patients with this condition (CAPS registry) and to analyse the value of the recently proposed preliminary criteria for the classification of catastrophic APS. METHODS: A review of the first 220 patients included in the website based CAPS registry was undertaken and the preliminary criteria for their classification were tested; 175 unselected patients with systemic lupus erythematosus or APS, or both, acted as controls. RESULTS: The mean age of the patients was 38 (14) years (range 7 to 74), with a female preponderance (F/M, 153/67). The main clinical manifestations included renal involvement in 154 (70%), pulmonary in 146 (66%), cerebral in 133 (60%), cardiac in 115 (52%), and cutaneous in 104 (47%); 114 patients (52%) recovered after the catastrophic APS event (mortality 48%). Patients who received the combination of anticoagulation plus steroids plus plasma exchange or intravenous immunoglobulins had the best survival rate (63%, p = 0.09). Sufficient data could be analysed for application of the classification criteria in 176 patients. According to the preliminary criteria, 89 patients (51%) could be classified as having "definite" and 70 (40%) as having "probable" catastrophic APS, thus given a sensitivity of 90.3% with a specificity of 99.4%. Positive and negative predictive values were 99.4% and 91.1%, respectively. CONCLUSIONS: The preliminary criteria for the classification of catastrophic APS and the CAPS registry are useful tools for epidemiological studies.

Adolescent↗
PubMed2005

Systemic autoimmune diseases co-existing with chronic hepatitis C virus infection (the HISPAMEC Registry): patterns of clinical and immunological expression in 180 cases.

OBJECTIVES: To describe the clinical and immunologic characteristics of a large series of patients with systemic autoimmune diseases (SAD) associated with chronic hepatitis C virus (HCV) infection. METHODS: We analysed 180 patients diagnosed with SAD and chronic HCV infection seen consecutively at our centres during the last 10 years. The clinical and immunological patterns of disease expression were compared with 180 SAD-matched patients without chronic HCV infection. RESULTS: A total of 180 HCV patients fulfilled the classification criteria for the following SAD: Sjogren's syndrome (n = 77), systemic lupus erythematosus (n = 43), rheumatoid arthritis (n = 14), antiphospholipid syndrome (n = 14), polyarteritis nodosa (n = 8) and other SAD (n = 24). One hundred and thirty (72%) patients were female and 50 (28%) male, with a mean age at SAD diagnosis of 50 years. The main immunologic features were antinuclear antibodies in 69% of patients, cryoglobulinaemia in 62%, hypocomplementaemia in 56% and rheumatoid factor (RF) in 56%. Compared with the SAD-matched HCV-negative group, SAD-HCV patients presented a lower prevalence of females (P = 0.016), an older age at SAD diagnosis (P = 0.039) and a higher prevalence of vasculitis (P < 0.001) and neoplasia (P < 0.001). Immunologically, SAD-HCV patients presented a lower prevalence of antinuclear (P = 0.036), anti-extractable nuclear antigen (P = 0.038) and anti-DNA (P = 0.005) antibodies, and a higher frequency of RF (P = 0.003), hypocomplementaemia (P < 0.001) and cryoglobulins (P < 0.001). CONCLUSIONS: In comparison with an SAD-matched HCV-negative population, SAD-HCV patients were older and more likely to be male, with a higher frequency of vasculitis, cryoglobulinaemia and neoplasia. This complex pattern of disease expression is generated by a chronic viral infection that induces both liver and autoimmune disease.

Antibodies, Antinuclear↗
PubMed2005

Antimitochondrial antibodies in patients with chronic hepatitis C virus infection: description of 18 cases and review of the literature.

To describe the clinical and immunologic patterns of disease expression of patients with chronic hepatitis C virus (HCV) infection and positive antimitochondrial antibodies (AMA). We investigated the presence of AMA in 237 consecutive HCV patients with extrahepatic manifestations from an International Registry. AMA were detected by indirect immunofluorescence in triple rat tissue (liver, stomach and kidney), aceton-fixed criosections and FITC-conjugated rabbit anti-human immunoglobulins. We found positive AMA in 18 (8%) out of 237 HCV patients. All patients were female with a mean age at protocol inclusion of 65.8 years (ranging from 37 to 87 years). Twelve (67%) patients fulfilled classification criteria for systemic autoimmune diseases (SAD), including Sjögren's syndrome (n = 7), systemic sclerosis (n = 3) and systemic lupus erythematosus (n = 2). Fourteen (78%) of the HCV-AMA patients presented at least one of the highly suggestive characteristics of primary biliary cirrhosis (PBC): 9 (50%) had a specific M2 pattern, 6 (33%) had more than twice normal levels of alkaline phosphatase, 5 (28%) had raised IgM levels and 4 (22%) a histological pattern compatible with PBC. Five (28%) patients developed neoplasia after detection of AMA. Seven (39%) patients died, due to neoplasia (n = 4), cirrhotic complications (n = 2) and hepatopulmonary syndrome (n = 1). We describe a subset of HCV patients with positive AMA who presented a broad spectrum of clinical features, including liver, autoimmune and neoplasic manifestations. Two-thirds of these patients presented an associated SAD, mainly Sjögren's syndrome or systemic sclerosis, together with a high frequency of multiple autoantibodies and an increased prevalence of cirrhosis and neoplasia.

Adult↗
PubMed2005

Disseminated intravascular coagulation in catastrophic antiphospholipid syndrome: clinical and haematological characteristics of 23 patients.

BACKGROUND: Disseminated intravascular coagulation (DIC) is an acquired syndrome characterised by formation of microthrombi and fibrin deposition in the microvasculature. The catastrophic antiphospholipid syndrome (APS) is characterised by multiorgan thrombosis, mainly involving small vessels. A broad spectrum of disorders may develop DIC features; however, the catastrophic APS has not previously been recognised as a cause of DIC. OBJECTIVE: To analyse the clinical and laboratory characteristics of catastrophic APS patients with DIC features. METHODS: The web site based international registry of patients with catastrophic APS (CAPS registry) (http://www.med.ub.es/MIMMUN/FORUM/CAPS.HTM) was analysed and the cases with DIC features selected. RESULTS: In 173 patients with catastrophic APS, 23 (13%) were found with DIC features. The clinical and immunological characteristics were similar in catastrophic APS patients with and without DIC features; a significant difference was found only in the prevalence of thrombocytopenia (100% in patients with DIC features v 59% in those without DIC features). CONCLUSIONS: DIC features are not rare in catastrophic APS, supporting the need for systematic screening of antiphospholipid antibodies in all patients with DIC features without precipitating factors. The presence of DIC features in the context of an APS makes it imperative to rule out the catastrophic variant of this syndrome.

Adolescent↗
PubMed2005

Mycophenolate mofetil in patients with hepatitis C virus infection.

Diagnosis and treatment of hepatitis C virus (HCV) -related autoimmune features has become a clinical challenge in HCV-infected patients, in whom chronic liver disease associated with severe autoimmune features may contribute to a very poor prognosis. Both antiviral and immunosuppressive therapies, either alone or in combination, seem likely to have a key role. Based on the experience of mycophenolate mofetil (MMF) use in HCV patients receiving organ transplantation, this new immunosuppressive agent might represent a safe and effective therapeutic option to treat HCV-related extrahepatic features. Recent data are available for the use of MMF in HCV patients with autoimmune manifestations, mainly for autoimmune cytopenias and vasculitic features. MMF may be used as monotherapy or in association with other drugs for cases of HCV-related autoimmune diseases refractory or intolerant to common immunosuppressive treatments, allowing the reduction of the drug dosage and avoiding serious side effects.

Antiviral Agents↗
PubMed2005

Multiple cartilaginous exostosis in a Golden Retriever cross-bred puppy. Clinical, radiographic and backscattered scanning microscopy findings.

Multiple cartilaginous exostosis was diagnosed in a six-month-old Golden Retriever cross-bred male with a history of forelimb lameness and isolated, but very painful, acute episodes. Physical examination revealed a right forelimb lameness with a firm, painful palpable mass on the cranial aspect of the forearm. The radiological examination showed the presence of bony masses at the humerus and radius as well as several masses in the ribs and spinous processes of the thoracic vertebrae. Based on the history and radiographic findings, multiple cartilaginous exostosis was diagnosed. Treatment with non-steroidal anti-inflammatory drugs was commenced for two weeks without any effect. Due to the lack of a response to the treatment as well as to the progressive physical deterioration of the animal, the owners requested euthanasia of the dog. Histology of the different exostoses demonstrated the presence of a hyaline cartilage cup surrounding a central area, formed mainly by bone and cartilage trabecullae. Signs of malignancy were not observed. Back-scattered scanning electron microscopy (BEI-SEM) study revealed well ordered and progressively calcified cartilage trabecullae present underneath the non-calcified cartilage cap. At a greater depth, those cartilage trabecullae became osteochondral trabecullae, and the innermost were formed exclusively by woven and lamellar bone. The histological and back-scattered electron scanning microscopy results conclude that it was a well-arranged normal endochondral ossification process that followed a centripetal pattern inside the bony mass, confirming the diagnoses of multiple cartilaginous exostoses.

Animals↗
PubMed2004

Primary Sjögren's syndrome: new clinical and therapeutic concepts.

Sicca features are the central clinical manifestations of Sjögren's syndrome (SS), but recent studies have confirmed that primary SS has a systemic expression, including extraglandular manifestations. Patients with a predominantly extraepithelial expression should be managed differently from patients with predominantly periepithelial or sicca limited disease. In coming years treatment will be based on muscarinic agonists for sicca features and immunosuppressive/biological agents for extraglandular features.

Humans↗
PubMed2004

Hypocomplementaemia as an immunological marker of morbidity and mortality in patients with primary Sjogren's syndrome.

OBJECTIVE: To analyse the prevalence and clinical significance of hypocomplementaemia in a large series of patients with primary Sjogren's syndrome (SS), focusing on the association of low complement levels with clinical manifestations, immunological features, lymphoproliferative disorders and mortality. METHODS: Complement determinations (C3 and C4 levels, CH50 activity) were made in 336 consecutive patients with primary SS (313 women and 23 men, mean age 58.5 yr). We also analysed complement levels in 46 patients with SS associated with hepatitis C virus (HCV) infection and 184 with HCV-related cryoglobulinaemia as control groups. RESULTS: Hypocomplementaemia was detected in 81 (24%) of patients with primary SS, low CH50 being detected in 51 (15%), low C3 values in 42 (12%) and low C4 values in 39 (12%). In the multivariate analysis, patients with low C4 levels showed a higher prevalence of peripheral neuropathy, cutaneous vasculitis, RF, cryoglobulins and lymphoma compared with those with normal C4 levels. The analysis of the 218 SS patients followed prospectively since 1994 showed a lower probability of survival in patients with hypocomplementaemia (with low C3, C4 or CH50 levels) at protocol entry. SS-HCV patients presented a higher frequency of hypocomplementaemia than patients with primary SS (76 vs 24%, P<0.001); nine (20%) of these patients had persistent, unquantifiable complement levels. CONCLUSION: Hypocomplementaemia is closely associated with systemic expression and adverse outcomes (lymphoma development and death) in patients with primary SS. Our results support the inclusion of complement determination at diagnosis as a predictor of the outcome of patients with primary SS and its routine determination in the clinical follow-up.

Aged↗