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J F Molina

Publications and source records attributed to J F Molina.

At least 19 recordsLinked to original sources

TAP1 and TAP2 polymorphisms analysis in northwestern Colombian patients with systemic lupus erythematosus.

OBJECTIVE: To determine the influence of TAP1 and TAP2 alleles in northwestern Colombian patients with systemic lupus erythematosus (SLE). METHODS: Unselected patients with SLE (n=140) and controls (n=120) matched for sex, age, and ethnicity were analysed. Clinical manifestations, clinical activity, and severity of disease were recorded. Autoantibodies were detected by enzyme linked immunosorbent assay (ELISA). TAP1 and TAP2 polymorphisms were determined by amplification refractory mutation system-polymerase chain reaction. A Hardy-Weinberg equilibrium test, microdifferentiation analysis, linkage disequilibrium analysis, and haplotype and allele frequency comparisons were performed. RESULTS: The TAP2 variant Val379/Ala565/Ala665 (allele TAP2*0201) was associated with SLE (56% v 39%; odds ratio=2, 95% confidence interval 1.22 to 3.30, p(c)=0.03). There was no stratification between patient and control samples. Linkage disequilibrium between TAP1 and TAP2 loci was found in controls but not in patients. An excess in the number of heterozygotes in the TAP2 locus was found in patients. No association between TAP1 and TAP2 variants and the presence of autoantibodies, clinical expression, or severity of disease was found. CONCLUSIONS: The TAP2 locus influences susceptibility to SLE in our patient group; however, it has no significant effect on the immune response or on the clinical course of the disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Relapsing polychondritis.

Relapsing polychondritis is a rare inflammatory disease of unknown aetiology characterized by recurrent inflammation and destruction of cartilaginous structures and connective tissue. Current data provide increasing support for an autoimmune basis, but its cause remains unknown. Individuals of any race, gender, or age may be affected, but it is most commonly seen between the ages of 40 and 60 years. Although relapsing polychondritis occurs predominantly as a separately defined clinical complex, a significant number of patients may suffer from another underlying rheumatic and/or haematological disorder; vasculitic syndromes are the most commonly observed disorders associated with relapsing polychondritis. Common clinical features are auricular, nasal and respiratory tract chondritis with involvement of organs of special sense, such as the eyes and audiovestibular apparatus. Polyarthritis and vasculitic involvement are also common. Corticosteroids are still the agents of choice although several other anti-inflammatory drugs can be used in order to allow tapering of the steroid dose or to achieve a lower maintenance dose for refractory cases.

Adrenal Cortex Hormones↗

Anticardiolipin and anti-beta2glycoprotein-I antibodies in patients with systemic lupus erythematosus: comparison between Colombians and Spaniards.

We studied the prevalence, isotype distribution, and clinical significance of anticardiolipin (aCL) and anti-beta2glycoprotein I (anti-beta2GPI) antibodies in two populations of patients with systemic lupus erythematosus (SLE), 160 Colombians and 160 Spaniards. All sera were tested in our laboratory by enzyme-linked immunosorbent assay (ELISA) for IgG, IgM, and IgA aCL, as well as IgG and IgM anti-beta2GPI. Positive results for at least 1 of the 3 aCL isotypes were found in 40 Colombians (25%) and 55 Spaniards (34%). IgG aCL was the predominant isotype in both populations. Positive results for at least 1 of the anti-beta2GPI isotypes were found in 34 Colombians (21%) and 29 Spaniards (18%). IgG anti-beta2GPI was the dominant isotype in Colombians, while IgM was predominant in Spaniards. Positivity for anti-beta2GPI in aCL-positive patients was present in 77% in the Colombian group and 50% in the Spaniard group. Among Colombians, IgG aCL and anti-beta2GPI correlated with thrombosis, fetal loss, and thrombocytopenia. Among Spaniards, IgG aCL and IgG anti-beta2GPI correlated with thrombosis, fetal loss, and livedo reticularis. For detecting thrombosis and fetal loss, aCL ELISA was more sensitive than anti-beta2GPI in Spaniards, and anti-beta2GPI ELISA was more specific than aCL in both populations.

Abortion, Spontaneous↗

Childhood-onset systemic lupus erythematosus: a comparative study of African Americans and Latin Americans.

This study compared the clinical and serologic features in two different ethnic groups of patients with childhood-onset systemic lupus erythematosus (SLE). One hundred seventy-one SLE patients comprised the study population; 61 (55 girls and 6 boys) were African American with age at onset of 13 +/- 2.9 years, and 110 (97 girls and 13 boys) were Latin American (Colombian) with age at onset of 13 +/- 3.2 years. Clinical, demographic, and laboratory data were obtained by chart review using a standard data collection form. African-American patients more commonly manifested discoid skin lesions, malar rash, pulmonary fibrosis, and pleuritis, and less commonly manifested photosensitivity, livedo reticularis, and vascular thrombosis than did Latin Americans. In addition, there was a higher frequency of anti-dsDNA, anti-Sm, anti-RNP, and anti-Ro positivity among African-Americans compared with Latin-American patients. These results suggest the presence of ethnic differences in the clinical expression of SLE.

Adenosine Triphosphatases↗

Anticardiolipin antibodies in childhood rheumatic disorders.

Anticardiolipin antibodies (aCL) have been reported to occur in a wide variety of autoimmune and non-autoimmune disorders in adults. Our objective was to investigate the prevalence and isotype distribution of aCL and its relationship with the features of antiphospholipid syndrome (APS) in childhood rheumatic disorders. Between November 1995 and May 1996, all patients who visited our paediatric rheumatology clinic whose guardians signed a consent form participated in the study. The study population included 106 patients (36 systemic lupus erythematosus (SLE), 28 juvenile rheumatoid arthritis (JRA), 11 fibromyalgia, 7 sarcoidosis, 5 dermatomyositis, 3 rheumatic fever (RF), 3 vasculitis, 2 scleroderma, and 11 miscellaneous). aCL measurements were performed by enzyme linked immunoabsorbent assay (ELISA). All patients were carefully evaluated for symptoms and signs of APS. Eighteen of the 106 patients (17%) were tested positive for one or more of the three aCL isotypes. In SLE, aCL were found positive in 13 of 36 (37%); in JRA 2 of 28 (7%); in sarcoidosis 2 of 7; and in RF 1 of 3. aCL of IgG isotype were found positive in 16 patients (11 SLE, 2 sarcoidosis, 2 JRA, and 1 RF). This isotype was usually detected at low titers (16-24 GPL). aCL of IgM isotype were found positive in five patients (2 sarcoidosis, 2 SLE, 1 JRA), and aCL of IgA isotype were found positive in only three patients (2 SLE, 1 sarcoidosis). Clinical features of APS were rarely seen in our SLE population and were not associated with the presence of aCL. None of the patients in the other groups exhibited any clinical manifestations of APS. In conclusion, aCL were found in 37% of our childhood SLE patients as compared with only 7% in JRA. These were mostly aCL of IgG isotype of low titers and therefore were not associated with the main features of APS. Prospective studies with a larger sample size may be needed to ascertain the exact prevalence and clinical significance of aCL in childhood-onset SLE.

Adolescent↗

Low-dose methotrexate therapy for childhood sarcoidosis.

OBJECTIVE: To evaluate the effectiveness of low oral doses of methotrexate as a steroid-sparing agent in children with sarcoidosis. STUDY DESIGN: An open-label, noncontrolled trial. Methotrexate was administered orally at a single weekly dose of 10 to 15 mg/m2. Duration of therapy was open ended, but patients received treatment for a minimum of 6 months to be considered as having completed the study. RESULTS: Seven children with biopsy-proven sarcoidosis completed the study. The mean dose of prednisone was successfully tapered from 49 mg/day (1.3 mg/kg) to 18 mg/day (0.5 mg/kg) after 3 months of methotrexate therapy and to 9.9 (0.2 mg/kg) and 7.3 mg/day (0.1 mg/kg) after 6 months and at the end of the follow-up period, respectively. Other clinical and laboratory parameters improved significantly after methotrexate therapy was started. There was significant clinical improvement, as confirmed by the reduction of the clinical severity score from 8 +/- 1.1 to 0.8 +/- 0.5 point after 3 months of methotrexate therapy, and to 0.7 and 0.5 +/- 0.3 point after 6 months and at the end of the follow-up, respectively. Laboratory measurements revealed marked improvement, as reflected by a significant reduction in the erythrocyte sedimentation rate and an increase of hemoglobin values. The mean serum angiotensin-converting enzyme activity dropped significantly. No adverse side effects were noted with methotrexate therapy. CONCLUSION: Our study demonstrated that low-dose oral methotrexate therapy was effective and safe and had steroid-sparing properties in seven children with sarcoidosis.

Administration, Oral↗

Induction of experimental antiphospholipid antibody syndrome in PL/J mice following immunization with beta 2 GPI.

PROBLEM: Immunization with beta 2-glycoprotein I (beta 2 GPI) induces antiphospholipid antibodies (aPL) in normal mice and rabbits. Recently we reported early onset of autoimmunity in MRL/(+2) mice following immunization with beta 2 GPI. There is a close association between aPL with thrombosis, recurrent fetal loss, and intrauterine growth retardation. In this study we evaluated the effect of beta 2 GPI-induced aPL on pregnancy outcomes in an inbred strain of mice (PL/J). METHOD: Three groups of seven-week female PL/J mice (12 per group) were studied. Group A was immunized with beta 2 GPI and group B with ovalbumin; group C was not not immunized. After two booster injections, the mice were tested for aPL, anti-DNA by ELISA, and for ANA by indirect immunofluorescence. Platelet count and pregnancy outcomes were studied at the age of 14 weeks. RESULTS: The aPL and anti-DNA levels were higher at 12 and 14 weeks in group A; the optical densities (OD) were 1.72 +/- 0.6 and 0.699 +/- 0.25 for group A, 0.09 +/- 0.040 and 0.230 +/- 0.47 for group B, and 0.0435 +/- 0.003 and 0.119 +/- 0.26 for group C (comparing group A with groups B and C combined, P < 0.001). ANA titers rose in groups A and B by age, but they were significantly higher at 14 weeks in group A. The mean titers were 1/286, 1/90, and 1/16 for A, B, and C, respectively (P < 0.001). The platelet counts were not significantly different among the three groups. The titer size was significantly smaller in group A, as evidenced by the numbers of viable fetuses among the mice that became pregnant in each group: 0.75, 2.45, and 5.5 in groups A, B, and C, respectively. Seven pregnant mice in group A had complete resorption, seven pregnant mice in group B showed focal (partial) resorption areas, by only one mouse in group C had complete resorption of the embryos, as shown by histopathological studies, although the fecundity rate was similar in the three groups. CONCLUSION: Our data suggest a pathogenic role for beta 2 GPI-induced aPL in the development of experimental models of APS in PL/J mice.

Animals↗

Ethnic differences in the clinical expression of systemic lupus erythematosus: a comparative study between African-Americans and Latin Americans.

Since ethnic differences in the disease expression of systemic lupus erythematosus (SLE) have been recognized, we compared the clinical and serological features in two different ethnic groups of patients with SLE. The study population consisted of 222 African-American and 300 Latin American (Colombian) SLE patients. Clinical, demographic, and laboratory data were obtained by chart review using a standard data collection form. African-American patients more commonly manifested discoid skin lesions, pulmonary fibrosis, and pleuritis, and less commonly manifested photosensitivity, livedo reticularis, and vascular thrombosis than did Latin Americans. In addition, there was a higher frequency of anti-Sm, anti-RNP, and anti-Ro positivity among African-American patients compared with Latin Americans. These results are additional evidence for the presence of ethnic differences in the clinical expression of SLE.

Adolescent↗

Variability of anticardiolipin antibody isotype distribution in 3 geographic populations of patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the prevalence of anticardiolipin antibodies (aCL) and isotype distribution and their clinical associations with the features of the antiphospholipid syndrome (APS) in 3 different ethnic groups of patients with systemic lupus erythematosus (SLE). METHODS: The study population consisted of 152 African-American, 136 Afro-Caribbean (Jamaican), and 163 Hispanic (Colombian) unselected patients with SLE. Serum samples were studied for the prevalence of aCL and isotype distribution. All aCL measurements were performed in the same laboratory by ELISA. RESULTS: Positive results for 1 of the 3 aCL isotypes were found in 42 African-Americans (28%), 28 Afro-Caribbeans (21%), and 43 Hispanics (26%). IgG aCL was the dominant isotype in Hispanic and African-American patients, while IgA was the dominant isotype in Afro-Caribbeans. Of note, IgA aCL was found in all Afro-Caribbean patients who were aCL positive, while only 3 patients in this group had IgG aCL and 2 had IgM aCL. Clinical features of the APS were found to correlate better in Hispanics than in African-Americans and Afro-Caribbean patients with aCL isotypes. CONCLUSION: Our data suggest the existence of ethnic differences in the prevalence and isotype distribution of aCL as well as in their clinical relevance in patients with SLE. Further studies of the role of genetic and/or environmental factors in the observed differences are required.

Adolescent↗

Longterm ultraviolet-A1 irradiation therapy in systemic lupus erythematosus.

OBJECTIVE: In a recent series of short term studies ultraviolet-A1 (UV-A1; 340-400 nm) dermal irradiation proved effective in reducing signs and symptoms of disease activity in patients with systemic lupus erythematosus (SLE). To determine if the effectiveness persisted with longterm therapy, we followed the progress of 6 of these patients for an average of 3.4 (range 2.4-4.5) yrs. The 6 had had significant decreases in signs and symptoms of disease activity during the first 12 weeks of the earlier studies while receiving 3 to 5 low dose UV-A1 irradiations weekly and were asked to continue into longterm therapy. METHODS: Longterm therapy consisted of 1 or 2 irradiations of 6-15 J/m2 (15-30 min, or about 1/8-1/4 minimal erythema dose) per week. We assessed their progress every 3 mo with the systemic lupus activity measures. RESULTS: Despite the smaller number of weekly treatments, the gains achieved during the initial 12 weeks of the early studies not only persisted but increased slightly. Tanning was moderate to absent, the therapy was well tolerated, and there was no apparent toxicity. CONCLUSION: UV-A1 radiation induced remissions in SLE persist with longterm therapy; 1 or 2 weekly exposures suffice; there appears to be no significant toxicity.

Follow-Up Studies↗

Pancytopenia secondary to methotrexate therapy in rheumatoid arthritis.

OBJECTIVE: To assess the frequency of methotrexate (MTX)-induced pancytopenia in rheumatoid arthritis (RA). METHODS: A MEDLINE literature search was conducted to identify articles published during the last 15 years (1980-1995) that presented data on MTX-associated pancytopenia. Two case reports of our own experience are also presented. In addition, articles that examined risk factors associated with MTX-related pancytopenia were identified. RESULTS: A total of 70 patients with pancytopenia related to MTX therapy were identified (68 reported in the literature, 2 from our own experience). Sixty-one of the patients were described in published case reports, 7 patients were from 5 long-term prospective studies. In many of these cases, predisposing factors for the development of pancytopenia were described. The 5 long-term prospective studies reported toxicity data on patients who had been treated with MTX for at least 13 weeks. A total of 511 patients were included in the prospective trials, yielding an overall incidence of pancytopenia of 1.4% (7 of 511). Of the 70 cases reported, 12 patients died (17%). Most of them had impaired renal function, hypoalbuminemia, concurrent infection, and/or concomitant medication with more than 5 drugs. The minimal cumulative MTX dose leading to fatal pancytopenia was 10 mg, observed in one of our patients. CONCLUSION: Pancytopenia is not an uncommon side effect of low-dose pulse MTX therapy in RA. It can lead to serious complications, including death.

Administration, Oral↗

Systemic lupus erythematosus in males. A study of 107 Latin American patients.

Clinical and laboratory features were analyzed in 107 Latin American male patients with systemic lupus erythematosus (SLE) who were compared with a group of 1,209 Latin American female patients with SLE to determine the presence of gender-associated differences. Males had an increased prevalence of renal disease, vascular thrombosis, and the presence of anti-dsDNA antibodies, as well as the use of moderate to high doses of corticosteroids, compared with female SLE patients. Although there was no difference in mortality from all causes, SLE-related mortality was higher in the male group. All these findings are consistent with a more severe disease in Latin American males than in female patients from the same region.

Adolescent↗

Prolactin-induced immunoglobulin and autoantibody production by peripheral blood mononuclear cells from systemic lupus erythematosus and normal individuals.

Prolactin (PRL) has been shown to have immunoregulatory effects on a variety of immune responses. Its effect on B cell immune responses is suggested by in vitro data demonstrating a direct effect on B cell activation and differentiation, and also in vivo data demonstrating a biphasic stimulation of antibody production to sheep red blood cells. In addition, it has been shown both in animal models and patients with hyperprolactinemia that PRL may influence the presence of certain autoantibodies. The objective of this work was to study the effect of PRL on the induction of immunoglobulins, and anti-DNA and rheumatoid factor (RF) autoantibody production from peripheral blood mononuclear cells (PBMCs) from normal individuals and systemic lupus erythematosus (SLE) patients. Six female SLE patients and 10 normal individuals (5 females and 5 males) were studied. Ficoll-Hypaque-isolated PBMCs (1x10(6) cells/ml) with high concentrations of PRL (10(-4)-10(-8)M) and pokeweed mitogen (PWM) diluted to 1:400. An ELISA assay was used for immunoglobulins, RF and anti-dsDNA antibodies. PRL stimulated IgG and IgM production in a biphasic manner in normal PBMCs. Enhanced synthesis was observed at 10(-6) M, and a stimulatory effect was again observed at higher doses of PRL (10(-4))M. In contrast, only a mild stimulatory effect was observed in IgG synthesis by SLE PBMCs. These changes in Ig synthesis, however, did not reach statistical significance. PRL also induced IgG and IgM anti-dsDNA antibodies by both normal and SLE lymphocytes, but no differences were observed when compared to PWM stimulation. PRL induced IgM RF synthesis by normal lymphocytes but had no effect on SLE PBMCs. This study demonstrates that PRL induced immunoglobulin synthesis by normal and to a lesser degree by SLE lymphocytes, and also induced anti-dsDNA antibody by normal and SLE PBMCs, and IgM RF by normal PBMCs. However, the exact mechanism(s) of PRL action on the immune response awaits elucidation.

Adult↗

Autoantibody profile in African-American patients with lupus nephritis.

Lupus nephritis (LN) is one of the major risk factors for morbidity and overall mortality in systemic lupus erythematosus (SLE). Its pathogenesis is multifactorial, and a number of risk factors, including serological markers, have been identified in recent years, correlating with clinical course and disease severity. Furthermore, a distinctive autoantibody profile has recently been reported in African-American SLE women with LN. The aim of this study was to characterize the autoantibody profile in 222 African-American SLE patients, 94 with LN and 128 without. Only anti-dsDNA achieved statistical significance between the two groups (P < 0.05). Fourteen (14.9%) patients with LN and 15 (11.7%) without it exhibited positive anti-Ro/SS-A, anti-Sm, and anti-nRNP, but without anti-La/SS-B (P > 0.6). We conclude that African-American SLE patients with LN do not exhibit a specific or distinctive autoantibody profile. However, our data confirm the value of anti-dsDNA in SLE patients with LN.

Adolescent↗

Protein losing enteropathy as the initial manifestation of childhood systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multisystem organ disease, and involvement of the gastrointestinal system is relatively rare. We describe a 13-year-old girl who presented initially with abdominal pain, diarrhea, edema, and hypoalbuminemia. She was diagnosed with protein losing enteropathy (PLE) based on the significant increase of alpha 1-antitrypsin clearance in the stool. Two weeks after admission she developed clinical and serological findings that fulfilled the ACR criteria for SLE. Over 22 cases of lupus associated PLE have now been reported, but only 3 in children. Children with PLE should be evaluated for SLE. In addition, PLE should be suspected as a possible cause of unexplained edema and/or hypoalbuminemia in SLE.

Adolescent↗

Silicone breast implant--associated musculoskeletal manifestations.

Three hundred consecutive women with silicone breast implants (SBI), referred to the arthritis clinic with a variety of musculoskeletal complaints, were evaluated for the presence of underlying connective tissue disease. A complete history and physical examination were performed, as well as laboratory testing for C-reactive protein, rheumatoid factor; and autoantibody determination by indirect immunofluorescence and immunodiffusion. The group mean age was 44.4 years (range 25-69), the mean time from initial implant surgery to appearance of symptoms was 6.8 years (range: 6m-19y) and 83.3% of women studied had clinical manifestations highly suggestive of an underlying connective tissue disorder. Fifty-four percent met criteria for fibromyalgia and/or chronic fatigue syndrome, distinct connective tissue diseases was detected in 11%, undifferentiated connective tissue disease or human adjuvant disease was found in 10.6%, and a variety of disorders such as angioneurotic oedema, frozen shoulder, multiple sclerosis-like syndrome were present. Several other miscellaneous conditions including recurrent unexplained low grade fever, hair loss, skin rash, sicca symptoms, Raynaud's phenomenon, carpal tunnel syndrome, memory loss, headaches, chest pain, and shortness of breath were also seen accompanying specific and non-specific conditions. Seventy percent of patients who underwent explanation of the implants reported improvement of their systemic symptomatology. A significant proportion of SBI patients referred for rheumatic evaluation have clinical manifestations highly suggestive of an underlying connective tissue disease. Furthermore, improvement of their symptomatology follows explanation of the implants in over half of the patients.

Adult↗

Ischemic optic neuropathy and high-level anticardiolipin antibodies in primary Sjögren's syndrome.

A 39-year-old woman with recurrent severe anterior ischemic optic neuropathy in the setting of Sjögren's syndrome was found to have high-titer IgM anticardiolipin antibodies (aCL) that were enhanced by the phospholipid-binding glycoprotein beta 2GP1. The recognition of IgM aCL-associated vasculopathy as a possible etiologic factor in the optic neuropathy in Sjögren's syndrome may be relevant in deciding appropriate therapy.

Adult↗