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ABSTRACT: Brain involvement in systemic lupus erythematosus (SLE) is a significant source of morbidity and mortality. Therefore, the early detection and treatment of brain involvement in SLE is of utmost importance; however, a confirmative diagnostic tool for neuropsychiatric SLE is yet to be developed. In this study, we investigated the efficacy of (18)F-FDG-PET for detection of brain involvement in patients with SLE with normal magnetic resonance imaging (MRI) findings. Twenty patients with SLE, who presented with neuropsychiatric symptoms despite normal brain MRI findings and who underwent brain (18)F-FDG-PET, were enrolled. The most common neuropsychiatric manifestation was headache (45%), followed by seizure (20%) and mood disorder (20%). (18)F-FDG-PET revealed significant glucose metabolic abnormalities in 15 of 20 patients (75%). The temporal (55%) and the occipital (55%) lobes were the most susceptible brain regions, followed by the frontal lobe (50%). However, neuropsychiatric symptoms were not geographically correlated to (18)F-FDG-PET findings. Two patients with abnormal (18)F-FDG-PET findings underwent follow-up brain (18)F-FDG-PET after remission, which showed complete resolution of abnormal glucose metabolism. Our data suggest that (18)F-FDG-PET may be an additional diagnostic modality complementary to MRI, when MRI is unable to provide evidence of brain involvement in patients with SLE.
Lupus 08/2012; · 2.34 Impact Factor
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ABSTRACT: To determine whether osteopontin (OPN) is increased in patients with AS and to investigate its relationship to inflammatory disease activity and bone remodelling process.
This cross-sectional study included 30 patients with AS and 23 age- and sex-matched healthy controls. We assessed clinical characteristics and laboratory parameters including the ESR, CRP, lipid profiles, the Bath AS disease activity index (BASDAI) and the Bath AS radiographic index (BASRI). To evaluate bone metabolism, we tested ALP, OCN and C-telopeptide of type I collagen (CTX-I). Plasma levels of OPN, TNF-alpha and IL-6 were measured by ELISA, and mRNA expression in peripheral blood mononuclear cells (PBMCs) was performed by RT-PCR. Changes in OPN level were also evaluated in eight patients after the treatment with a TNF-alpha blocker.
Patients with AS had significantly higher plasma OPN, TNF-alpha and IL-6 levels and more mRNA expression than healthy controls. Plasma OPN levels were correlated with serum ALP, OCN and CTX-I levels, but not with ESR, CRP, lipid profiles, BASDAI or BASRI. Treatment with a TNF-alpha blocker did not alter OPN levels, although it reduced the disease activity.
Patients with AS had higher levels of OPN compared with controls. The plasma OPN level was correlated with serum ALP, OCN and CTX-I levels, but not with disease activity in AS. OPN might be involved in bone remodelling rather than in inflammation in AS.
Rheumatology (Oxford, England) 11/2008; 47(12):1775-9. · 4.24 Impact Factor
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ABSTRACT: To investigate whether the ratio of mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (E') (E/E' ratio) can detect left ventricular diastolic dysfunction more sensitively than the ratio of E to mitral peak velocity of late filling (A) (E/A ratio) in systemic lupus erythematosus (SLE). A total of 137 patients with SLE were investigated and compared with 110 age-matched and sex-matched controls retrospectively. Two-dimensional echocardiography and M-mode echocardiography including conventional and tissue Doppler imaging were performed. There were no differences in the left ventricle ejection fractions and the mean E/A ratio between the two groups. However, the mean E/E' ratio of patients was higher than that of the controls (10.4 +/- 4.0 vs 7.7 +/- 2.1, P < 0.01). Significantly higher left ventricle ejection fractions and lower E/E' ratio were found in patients with systemic lupus erythematosus receiving angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker than those not receiving (P < 0.05). Our study showed that the E/E' ratio is more sensitive than the E/A ratio for detection of the left ventricle diastolic dysfunction. Furthermore, patients who had received angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker treatment showed significantly better preservation of both systolic and diastolic function of left ventricle in comparison with those who had not received.
Lupus 01/2008; 17(3):195-201. · 2.34 Impact Factor
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ABSTRACT: To investigate the outcome of vascular interventions and the effect of post-interventional immunosuppressive treatment on the occurrence of vascular restenosis in patients with Takayasu's arteritis (TA).
Forty-two patients with TA who had undergone vascular intervention and had serial angiographies before and after intervention were enrolled. The demographic and clinical data were collected at the time when the interventions were performed, and the intervention modalities and post-interventional medical treatments were evaluated.
Sixty-three interventions were performed in 42 patients. Twenty (31.7%) interventions restenosed 24.0 +/- 21.9 months after intervention; the likelihood decreasing as time passed. Estimates of arterial patency after intervention were 90.1% at 1 yr, 75.5% at 2 yr, 68.4% at 3 yr, 61.6% at 5 yr and 49.3% at 10 yr. According to the log rank test, interventions that were performed during the stable stage of the disease (P = 0.039) and those that were followed by treatment with glucocorticoids and immunosuppressive agents (P = 0.044) were independent variables for the maintenance of arterial patency. Their hazard ratios were 0.30 and 0.41, respectively.
Restenosis occurred in 31.7% of TA patients after intervention. A lower restenosis rate was observed when the vascular interventions were performed at the stable stage and when post-interventional immunosuppressive treatment was implemented.
Rheumatology 06/2006; 45(5):600-5. · 4.06 Impact Factor
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ABSTRACT: To investigate serum profiles of inflammatory cytokines in patients with Takayasu's arteritis (TA) and to determine their correlations with disease activity of TA.
Forty-nine patients with TA and 12 age- and sex-matched controls were studied. Blood samples were obtained and were divided into active and stable disease groups. Paired blood samples were available in 19 patients at the active stage before treatment and at the remitted stage after treatment. Serum tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-6, IL-12 and IL-18 levels were determined by enzyme-linked immunosorbent assay.
Serum TNF-alpha, IL-6 and IL-18 levels of patients with TA were significantly higher than those of controls (P<0.05), but IFN-gamma and IL-12 levels were not. Serum IL-6 and IL-18 levels were significantly higher in the active disease group than in the stable disease group (P<0.05), but the levels of TNF-alpha were not different between the groups. In the 19 patients with paired samples, serum IL-18 levels at the remitted stage after treatment were significantly decreased compared with the active stage before treatment (P<0.001). The changes in IL-18 levels between active and remitted stages correlated well with changes in erythrocyte sedimentation rate (P<0.001).
Serum IL-18 and IL-6 levels were elevated in patients with TA, especially in those with active disease. Serum IL-18 levels correlated well with disease activity of TA. These results suggest that IL-6 and IL-18 might contribute to the pathogenesis of TA and that IL-18 could be a useful marker for monitoring disease activity of TA.
Rheumatology 05/2006; 45(5):545-8. · 4.06 Impact Factor
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ABSTRACT: This study was designed to investigate the risk of ovarian failure and the pregnancy outcomes in women treated with intravenous cyclophosphamide (IVCYC) pulse therapy for lupus nephritis. Sixty-seven women with proliferative lupus nephritis were studied. The clinical and laboratory data, SLEDAI and damage indices at IVCYC initiation, doses and numbers of IVCYC pulses, pregnancy and fetal outcomes were evaluated. During a follow-up of 74.4+/-20.6 months, amenorrhea occurred in 25 (37.3%) and was sustained permanently in 10 patients (14.9%). Thirteen women became pregnant with a total of 19 pregnancies. Seventeen pregnancies ended without complications and all babies were born healthy without any congenital anomalies or perinatal illnesses. Two pregnancies were terminated by induced abortion but no congenital anomaly was noted in these cases. Logistic regression analysis showed that old age, high damage index at the initiation of IVCYC pulse therapy and high cumulative dosage of IVCYC were the independent risk factors of ovarian failure, and that the presence of amenorrhea, regardless of its duration, was the risk factor of pregnancy failure. Pregnancy was possible with a favorable outcome after the withdrawal of IVCYC pulse therapy, unless amenorrhea develops.
Lupus 02/2004; 13(8):569-74. · 2.34 Impact Factor
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ABSTRACT: A case of primary non-Hodgkin's malignant lymphoma of the vulva which occurred in a 68-year-old woman is presented. Non-Hodgkin's malignant lymphoma is infrequently involved in the female genital tract. Moreover, primary vulvar involvement of this tumor is very rare. To date only 6 cases have been reported in the literature. To our knowledge this is the first reported case of a non-Hodgkin's malignant lymphoma of the vulva in Korea.
Journal of Korean Medical Science 10/1992; 7(3):271-5. · 0.99 Impact Factor
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ABSTRACT: Cardiovascular manifestations have been reported in 7-38% of patients with Behçet's disease (BD), and mortality occurs in up to 20% of those with marked vascular involvement. Sporadic cases of endocarditis, myocarditis, pericarditis, acute myocardial infarction, aortic aneurysm, ventricular thrombosis, congestive cardiomyopathy, and valvular dysfunction have been reported. Here we report a case of acute myocardial infarction that resulted from the compression of coronary arteries by a sinus of Valsalva aneurysm in a patient with BD.
Clinical and experimental rheumatology 26(4 Suppl 50):S117-20. · 2.15 Impact Factor
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ABSTRACT: To determine the association between angiogenic factor mRNA expression and disease activity and radiographic damage in patients with rheumatoid arthritis (RA).
We enrolled 42 RA patients and assessed their disease activity (DAS28) and Larsen scores. We used a semi-quantitative reverse transcriptase-polymerase chain reaction to measure levels of angiogenin, endoglin, survivin and angiomotin mRNA in peripheral blood mononuclear cells (PBMCs) from 42 patients and in fibroblasts-like synoviocytes (FLS) from 14 RA patients. Then, we compared the angiogenic factor mRNA expression levels and parameters for disease activity and radiographic damage between RA patients and 42 healthy controls. We also compared the mRNA levels from FLS between 14 RA patients and 12 osteoarthritis (OA) patients.
PBMCs from RA patients showed increased expression of survivin and angiomotin mRNA compared to controls, while rheumatoid FLS showed increased expression for all genes tested compared to OA FLS. Angiogenin, endoglin, and angiomotin mRNA levels of PBMCs did not show any significant correlation with DAS28, but the survivin mRNA level in PBMCs showed a significant positive correlation with DAS28 (p=0.003) and Larsen scores (p=0.012). Survivin was the only angiogenic factor that showed a significant association with the Larsen score.
The systemic and local production of angiogenic factors are increased in patients with RA and, of the genes tested in this study, survivin gene expression correlated well with disease activity and radiographic damage in patients with RA.
Clinical and experimental rheumatology 26(5):881-6. · 2.15 Impact Factor
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Clinical and experimental rheumatology 24(3):347. · 2.15 Impact Factor
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ABSTRACT: To investigate the prevalence of anti-endothelial cell antibodies (AECA) and antiphospholipid antibodies, and the correlations of their isotype distributions and titers with disease activity in patients with Takayasu's arteritis (TA).
Forty-seven patients with TA and 30 age- and sex-matched controls were studied. Blood samples were obtained from all patients and they were divided into either active or stable disease groups. Paired samples were available in 18 patients at both active and stable stage, respectively. AECA against human umbilical vein endothelial cells and antiphospholipid antibodies were measured.
Forty-two (89.4%) TA patients had AECA, and positivity rates of IgM and IgG AECA were 83.0% and 68.1%, respectively, while those for controls were both 3.3%. The titers of IgM and IgG AECA in patients were significantly higher than those in controls. IgM AECA titers of the active group were significantly higher than those of the stable group, but IgG AECA titers were not. In 18 patients with paired samples, IgM AECA titers at active stage were significantly higher than those at stable stage, but IgG AECA titers were not different between stages. The changes of IgM AECA titers correlated well with those of ESR levels between stages. Antiphospholipid antibodies were detected in only 4 patients with TA, but not in controls.
IgM AECA and IgG AECA were more prevalent and their titers were higher in patients with TA than in controls, and IgM AECA titers correlated well with the disease activity of TA. Antiphospholipid antibodies were not found significant.
Clinical and experimental rheumatology 24(2 Suppl 41):S10-6. · 2.15 Impact Factor
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ABSTRACT: To investigate the clinical characteristics and outcomes of Takayasu's arteritis (TA) using standardized criteria for diagnosis, disease activity, and angiographic classification, and to identify the predictive factors for remission, angiographic progression, and mortality in patients with TA.
One hundred and eight patients who fulfilled the 1990 American College of Rheumatology (ACR) classification criteria for TA were studied. Their clinical features, laboratory findings, angiographic findings, and clinical outcomes were evaluated retrospectively. The disease activities were assessed using the National Institutes of Health (NIH) criteria for active disease, and the angiographic types were classified using the International TA Conference in Tokyo 1994 angiographic classification.
Angiographic classification showed that type I was the most common, followed by types V and IV. Ninety-one patients had active disease at diagnosis, and remission was achieved in 81.3% of them. Among those who experienced remission and those who had stable disease at diagnosis, 28.6% experienced a relapse. A low erythrocyte sedimentation rate (ESR) at diagnosis and treatment with glucocorticoid were found to be independent predictors for remission, and the stable disease activity at diagnosis was an independent predictor for the quiescence of vascular lesions on follow-up angiography. Survival rates were 92.9% at the fifth year and 87.2% at the tenth year, and the presence of two or more complications was a risk factor for mortality.
These findings could provide useful information on the clinical features, angiographic findings, and outcomes in TA, particularly on the assessment of patients at risk of a poor outcome.
Scandinavian Journal of Rheumatology 34(4):284-92. · 2.47 Impact Factor
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ABSTRACT: Adult onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown cause characterized by high fever accompanied by systemic manifestations. Since AOSD consists of heterogeneous symptoms and has no definite diagnostic tool, the diagnosis is based upon exclusive criteria. Dermatopathic lymphadenopathy (DL) is characterized by a localized paracortical proliferation of histiocytes and deposition of melanin in the lymph nodes. DL is not only a reactive hyperplasia of the lymph nodes, but has also been reported to be associated with hematological malignancies such as cutaneous T cell lymphoma (CTCL) and Hodgkin's lymphoma. It is therefore important to evaluate CTCL or Hodgkin's lymphoma in a patient with DL, in order to both rule out hematological malignancy and diagnose AOSD. In this report, we first describe a 37-year-old patient with AOSD whose biopsy of lymph node was proved to be DL.
Clinical and experimental rheumatology 25(2):312-4. · 2.15 Impact Factor
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ABSTRACT: To determine serum concentrations of bone morphogenetic proteins (BMPs) in patients with ankylosing spondylitis (AS) and to investigate their relationship to disease activity, spinal dysmobility, and spinal damage.
Serum samples from 40 AS patients, 40 rheumatoid arthritis (RA) patients, and 40 healthy subjects were obtained, and serum BMP-2, -4, and -7 levels were determined by enzyme-linked immunosorbent assay (ELISA). Clinical measurements for AS patients included the Bath AS Disease Activity Index (BASDAI), Metrology Index (BASMI), and Radiographic Index (BASRI), and those for RA patients included the disease activity score (DAS) 28 and Larsen scores. Sample collections and clinical assessments were performed at baseline and after a mean follow-up of 51.7+/-19.7 months.
At baseline, both AS and RA patients demonstrated significantly elevated serum BMP-2 and BMP-7 levels compared with healthy controls (p<0.05). In AS patients, baseline BMP-2 levels correlated well with BASDAI (p<0.05), and BMP-7 levels correlated with BASRI-spine (p<0.05). However, no BMP levels showed significant correlation with DAS28 and Larsen scores in RA patients. The changes in BMP-7 levels from baseline to after the follow-up period showed a significant correlation with the changes of BASRI-spine, but the changes in other BMPs did not show any significant relationship to the changes in clinical parameters.
Overproduction of BMP-2 and BMP-7 was noted in AS patients, and serum BMP-7 levels reflected radiographic damage observed in AS.
Scandinavian Journal of Rheumatology 37(3):200-4. · 2.47 Impact Factor
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ABSTRACT: Adiponectin (AD) is considered an inflammation modulator. In this study, we investigated the effect of AD on rheumatoid arthritis (RA) using a collagen-induced arthritis (CIA) mouse model and RA synovial fibroblasts (RASF).
Fifteen DBA/1 mice were divided into three groups. All mice, except the control group, were injected with type II collagen. AD was intra-articularly injected in the left hind legs after arthritis development (the AD-treated group). The severity of the arthritis was measured using an arthritis score and paw thickness. A histopathological assessment of joint sections was performed by haematoxylin/eosin (H&E) staining. Tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and matrix metalloproteinase (MMP)-3 expression was evaluated by immunohistochemical staining in the CIA mice. Synovial tissue was obtained from four RA patients during total joint replacement. RASF cultures were established from this tissue. RASF were pretreated with AD and stimulated by TNFalpha or IL-1beta. TNFalpha, IL-1beta, IL-6, and MMP-3 production was measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR). RASF proliferation was evaluated using the MTT assay.
AD significantly mitigated the severity of the arthritis and histopathological findings indicative of RA in CIA mice. TNFalpha, IL-1beta, and MMP-3 expression decreased, but IL-6 expression in AD-treated joint tissues increased. Moreover, AD reduced TNFalpha, IL-1beta, and MMP-3 expression in stimulated RASF and increased IL-6 expression in IL-1beta-stimulated RASF. AD significantly inhibited IL-1beta-induced RASF proliferation, despite increased IL-6 expression.
These data suggest that AD may play an anti-inflammatory role in the pathophysiology of RA.
Scandinavian Journal of Rheumatology 37(4):260-8. · 2.47 Impact Factor
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ABSTRACT: To determine the serum concentration of tumour necrosis factor (TNF)-related weak inducer of apoptosis (TWEAK) in patients with rheumatoid arthritis (RA) and to investigate the relationship between TWEAK level and disease activity, proinflammatory cytokine levels, and response to anti-TNF treatment.
Serum samples from 40 patients with RA, 40 patients with ankylosing spondylitis (AS), and 40 healthy subjects were collected. Serum samples from 26 patients with RA who received etanercept treatment were also collected in the 12th week of etanercept therapy. Serum TWEAK, TNFalpha, and interleukin (IL)-6 levels were determined by enzyme-linked immunosorbent assay (ELISA), and disease activity of RA was assessed according to the 28-joint count Disease Activity Score (DAS28).
Patients with RA had significantly higher serum levels of TWEAK, TNFalpha, and IL-6 compared with controls (p<0.05). Patients with AS also had significantly higher serum levels of TNFalpha and IL-6 (p<0.05), but their serum TWEAK levels were not different from those of the controls. In patients with RA, serum TWEAK levels correlated with DAS28 (r(2) = 0.452, p = 0.012) and TNFalpha levels (r(2) = 0.653, p<0.001) but not with IL-6 levels. Among RA patients who were treated with etanercept, responders showed a significant decrease in serum TWEAK levels at the 12th week of treatment, whereas TWEAK levels in nonresponders were not different from their baseline levels.
Serum levels of TWEAK were significantly elevated in patients with RA, and reflected disease activity and short-term response to etanercept treatment.
Scandinavian Journal of Rheumatology 37(3):173-8. · 2.47 Impact Factor
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ABSTRACT: To determine whether serum leptin levels are elevated in men with ankylosing spondylitis (AS) and whether the levels correlate with serum cytokine profiles and disease activity of AS.
Forty-two male patients with newly diagnosed AS were enrolled. Their Bath AS Disease Activity Index (BASDAI), body mass index (BMI), and acute phase reactants, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, were assessed. Serum leptin levels were determined using radioimmunoassay (RIA) and serum cytokine profiles, including tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, and interferon (IFN)-gamma, were determined using enzyme-linked immunosorbent assay (ELISA). These results were compared with those from 42 age-matched healthy men. After a follow-up period of 31.0+/-20.1 months, clinical and biochemical variables were reassessed in the men with AS.
At baseline, patients with AS had significantly elevated serum levels of leptin, leptin adjusted for BMI (leptin/BMI), TNFalpha, and IL-6, but not IFN-gamma, as compared to the controls. Serum leptin/BMI levels correlated well with IL-6 levels, and both leptin/BMI and IL-6 levels correlated well with BASDAI and CRP levels in patients with AS. The changes in leptin/BMI and IL-6 levels between the baseline and follow-up measurements correlated well with one another (p<0.05) and both correlated well with the changes in BASDAI (p<0.05).
Serum leptin/BMI levels were increased and significantly associated with IL-6 levels and disease activity in men with AS, suggesting a possible role for leptin in the inflammatory reactions of AS.
Scandinavian Journal of Rheumatology 36(2):101-6. · 2.47 Impact Factor
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ABSTRACT: In this study, we investigated the HLA allele and haplotype frequencies, and the association of HLA alleles with serious complications and angiographic findings in Korean patients with Takayasu arteritis (TA) compared with healthy controls. Sixty-one patients (56 women, 5 men), diagnosed with TA between January 1995 and December 2005, were studied. Ninety-five healthy men and women were selected as controls. Clinical manifestations were assessed and angiographies were performed at the time of diagnosis in all TA patients. Genotypes of the HLA-A, -B and -DRB1 loci were determined using the polymerase chain reaction-sequencing-based typing (PCR-SBT) method. The mean age at the time of diagnosis of TA was 37.0+/-12.1 years. Compared with controls, the frequencies of A*3001 (p=0.048), B*5201 (p=0.025), and DRB1*1502 (p=0.046) alleles were significantly higher in TA patients, and the frequency of A*2602 was significantly lower in TA patients when compared with controls (p=0.047). The haplotype containing A*2402-B*5201-DRB1*1502 was significantly increased in TA patients (chi2=5.45, p=0.01). Further, among the serious complication of TA, congestive heart failure (CHF) was found to be associated with B*5201 (OR=5.94, p<0.05, 95% CI=1.04 33.85). These data suggest that A*3001, B*5201, and DRB1*1502 alleles might increase the susceptibility to TA, while A*2602 might protect against TA. Further, our results reveal that the haplotype A*2402-B*5201-DRB1*1502 could be a risk factor for TA, and the allele B*5201 is significantly associated with CHF.
Clinical and experimental rheumatology 25(1 Suppl 44):S18-22. · 2.15 Impact Factor
