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1.
Sci Rep ; 10(1): 1510, 2020 01 30.
Article in English | MEDLINE | ID: mdl-32001732

ABSTRACT

Electrolytic ablation (EA) is a promising nonthermal tumor ablation technique that destroys malignant cells through induction of a locoregional pH change. EA is typically performed by inserting needle electrodes inside the tumor followed by application of direct current (DC), thus inducing electrolysis and creating localized pH changes around the electrodes. In this paper, we report an ultrasonically powered implantable EA microprobe that may increase the clinical relevance of EA by allowing wireless control over device operation (capability to remotely turn the device on and off) and providing flexibility in treatment options (easier to administer fractionated doses over a longer period). The wireless EA microprobe consists of a millimeter-sized piezoelectric ultrasonic receiver, a rectifier circuit, and a pair of platinum electrodes (overall size is 9 × 3 × 2 mm3). Once implanted through a minimally invasive procedure, the microprobe can stay within a solid tumor and be repeatedly used as needed. Ultrasonic power allows for efficient power delivery to mm-scale devices implanted deep within soft tissues of the body. The microprobe is capable of producing a direct current of 90 µA at a voltage of 5 V across the electrodes under low-intensity ultrasound (~200 mW/cm2). The DC power creates acidic (pH < 2) and alkaline (pH > 12.9) regions around the anode and the cathode, respectively. The pH change, measured using tissue-mimicking agarose gel, extends to 0.8 cm3 in volume within an hour at an expansion rate of 0.5 mm3/min. The microprobe-mediated EA ablative capability is demonstrated in vitro in cancer cells and ex vivo in mouse liver.

2.
Lupus ; 21(14): 1531-7, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22941565

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.


Subject(s)
Brain/physiopathology , Lupus Vasculitis, Central Nervous System/diagnosis , Magnetic Resonance Imaging/methods , Positron-Emission Tomography/methods , Adult , Female , Fluorodeoxyglucose F18 , Humans , Lupus Vasculitis, Central Nervous System/physiopathology , Male , Radiopharmaceuticals
3.
Clin Exp Rheumatol ; 30(3 Suppl 72): S18-26, 2012.
Article in English | MEDLINE | ID: mdl-22776346

ABSTRACT

OBJECTIVES: Cardiovascular surgery in patients with Behçet's disease (BD) frequently leads to postoperative complications such as anastomotic leakage, occlusion or pseudoaneurysm. We evaluated the clinical outcomes and related risk factors of postoperative complications in BD patients undergoing cardiovascular surgeries, as well as the long-term efficiency of postoperative immunosuppressive treatment. METHODS: Forty-one patients with BD who had undergone cardiovascular surgery between 1990 and 2009 were studied. We evaluated the patients' clinical data, postoperative complications, and survival rate. Risk factors related to the occurrence of postoperative complications were identified by univariate analysis using the Kaplan-Meier method with the log-rank test and multivariate analysis using the Cox proportional hazards regression model. RESULTS: Fifty-nine operations were performed in 41 patients. During the mean follow-up period of 65.3±48.1 months, complications such as paravalvular leakage, dehiscence, fistula, graft occlusion, or pseudoaneurysm occurred in 29 operations (49.2%). The cumulative occurrence rate of postoperative complication was 10.2% at three months, 32.8% at 12 months, and 43.8% at 24 months. Upon univariate analysis, young age, high Creactive protein levels, lack of postoperative immunosuppression, and short disease duration were identified as significant factors responsible for the occurrence of postoperative complications. In multivariate analysis, postoperative immunosuppression was found to independently lower the risk of complications. The 5-year survival rate was significantly higher in patients with postoperative immunosup immunosuppression than in those without (84.5% vs. 45.0%, p=0.011). CONCLUSIONS: The present study suggests that postoperative immunosuppressive therapy after cardiovascular surgeries in BD patients is important for reducing the development of serious postoperative complications.


Subject(s)
Behcet Syndrome/complications , Cardiac Surgical Procedures/adverse effects , Cardiovascular Diseases/surgery , Postoperative Complications/etiology , Vascular Surgical Procedures/adverse effects , Adult , Behcet Syndrome/drug therapy , Behcet Syndrome/mortality , Cardiac Surgical Procedures/mortality , Cardiovascular Diseases/etiology , Cardiovascular Diseases/mortality , Female , Humans , Immunosuppressive Agents/therapeutic use , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Postoperative Complications/mortality , Postoperative Complications/prevention & control , Proportional Hazards Models , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Vascular Surgical Procedures/mortality
4.
J Hand Surg Eur Vol ; 34(5): 685-8, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19959449

ABSTRACT

We report 17 patients with a subungual glomus tumour. All complained of pain and tenderness when touched, and nine patients experienced severe pain in the cold. A transungual approach with nail plate avulsion on one side was used in all cases. A surgical microscope was used to localise and dissect the tumour and to repair the nail bed and matrix. This method has produced good results, without local recurrence or postoperative nail plate deformity.


Subject(s)
Glomus Tumor/diagnosis , Glomus Tumor/surgery , Microsurgery , Nail Diseases/surgery , Skin Neoplasms/diagnosis , Skin Neoplasms/surgery , Adult , Cohort Studies , Female , Humans , Male , Microdissection , Middle Aged , Nail Diseases/diagnosis , Nails, Malformed/prevention & control , Retrospective Studies , Treatment Outcome
5.
Clin Exp Rheumatol ; 26(5): 881-6, 2008.
Article in English | MEDLINE | ID: mdl-19032823

ABSTRACT

OBJECTIVE: To determine the association between angiogenic factor mRNA expression and disease activity and radiographic damage in patients with rheumatoid arthritis (RA). METHODS: 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. RESULTS: 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. CONCLUSION: 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.


Subject(s)
Angiogenesis Inducing Agents/blood , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/diagnostic imaging , Angiomotins , Antigens, CD/genetics , Antigens, CD/metabolism , Arthritis, Rheumatoid/genetics , Case-Control Studies , Endoglin , Fibroblasts/metabolism , Humans , Inhibitor of Apoptosis Proteins , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Leukocytes, Mononuclear/immunology , Membrane Proteins/genetics , Membrane Proteins/metabolism , Microfilament Proteins , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , Osteoarthritis/genetics , RNA, Messenger/immunology , RNA, Messenger/metabolism , Radiography , Receptors, Cell Surface/genetics , Receptors, Cell Surface/metabolism , Ribonuclease, Pancreatic/genetics , Ribonuclease, Pancreatic/metabolism , Severity of Illness Index , Survivin , Synovial Membrane/metabolism
6.
Clin Exp Rheumatol ; 26(4 Suppl 50): S117-20, 2008.
Article in English | MEDLINE | ID: mdl-19026129

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.


Subject(s)
Aortic Aneurysm/complications , Behcet Syndrome/complications , Myocardial Infarction/etiology , Sinus of Valsalva , Aortic Aneurysm/pathology , Female , Humans , Middle Aged , Sinus of Valsalva/pathology
7.
Rheumatology (Oxford) ; 47(12): 1775-9, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18854347

ABSTRACT

OBJECTIVES: To determine whether osteopontin (OPN) is increased in patients with AS and to investigate its relationship to inflammatory disease activity and bone remodelling process. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
Bone Remodeling , Osteopontin/physiology , Spondylitis, Ankylosing/physiopathology , Adult , Antibodies, Monoclonal/therapeutic use , Antirheumatic Agents/therapeutic use , Biomarkers/blood , Cross-Sectional Studies , Cytokines/blood , Cytokines/genetics , Etanercept , Female , Gene Expression , Humans , Immunoglobulin G/therapeutic use , Infliximab , Interleukin-6/blood , Male , Middle Aged , Osteopontin/blood , Osteopontin/genetics , RNA, Messenger/genetics , Receptors, Tumor Necrosis Factor/therapeutic use , Reverse Transcriptase Polymerase Chain Reaction/methods , Severity of Illness Index , Spondylitis, Ankylosing/blood , Spondylitis, Ankylosing/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/blood , Young Adult
8.
Scand J Rheumatol ; 37(4): 260-8, 2008.
Article in English | MEDLINE | ID: mdl-18612926

ABSTRACT

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: These data suggest that AD may play an anti-inflammatory role in the pathophysiology of RA.


Subject(s)
Adiponectin/physiology , Arthritis, Experimental/pathology , Arthritis, Experimental/physiopathology , Synovial Membrane/pathology , Animals , Female , Fibroblasts/physiology , Humans , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Knee Joint/physiopathology , Matrix Metalloproteinase 3/metabolism , Mice , Tumor Necrosis Factor-alpha/metabolism
9.
Scand J Rheumatol ; 37(3): 173-8, 2008.
Article in English | MEDLINE | ID: mdl-18465450

ABSTRACT

OBJECTIVES: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: Serum levels of TWEAK were significantly elevated in patients with RA, and reflected disease activity and short-term response to etanercept treatment.


Subject(s)
Arthritis, Rheumatoid/blood , Interleukin-6/blood , Spondylitis, Ankylosing/blood , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factors/blood , Adult , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Case-Control Studies , Cytokine TWEAK , Etanercept , Female , Humans , Immunoglobulin G/therapeutic use , Male , Middle Aged , Receptors, Tumor Necrosis Factor/therapeutic use , Severity of Illness Index , Spondylitis, Ankylosing/drug therapy , Treatment Outcome
10.
Scand J Rheumatol ; 37(3): 200-4, 2008.
Article in English | MEDLINE | ID: mdl-18465455

ABSTRACT

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Overproduction of BMP-2 and BMP-7 was noted in AS patients, and serum BMP-7 levels reflected radiographic damage observed in AS.


Subject(s)
Arthritis, Rheumatoid/blood , Bone Morphogenetic Proteins/blood , Bone and Bones/metabolism , Movement , Spondylitis, Ankylosing/blood , Adult , Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/physiopathology , Bone and Bones/diagnostic imaging , Case-Control Studies , Female , Humans , Male , Middle Aged , Mobility Limitation , Radiography , Severity of Illness Index , Spondylitis, Ankylosing/diagnostic imaging , Spondylitis, Ankylosing/physiopathology
11.
Lupus ; 17(3): 195-201, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18372359

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.


Subject(s)
Diastole , Lupus Erythematosus, Systemic/complications , Ventricular Dysfunction, Left/diagnosis , Adult , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Female , Humans , Lupus Erythematosus, Systemic/physiopathology , Male , Middle Aged
12.
Acta Neurochir Suppl ; 97(Pt 2): 407-16, 2007.
Article in English | MEDLINE | ID: mdl-17691329

ABSTRACT

Treatment-resistant depression (TRD) is a major public health concern due to its high costs to society. One of the novel approaches for the treatment of depression is the vagus nerve stimulation (VNS). Therapeutic brain stimulation through delivery of pulsed electrical impulses to the left cervical vagus nerve now has established safety and efficacy as an adjunct treatment for medication-resistant epilepsy and has recently been approved as an adjunct long-term treatment for chronic or recurrent depression. There is considerable evidence from both animal and human neurochemical and neuroimaging studies, that the vagus nerve and its stimulation influence limbic and higher cortical brain regions implicated in mood disorders, providing a rationale for its possible role in the treatment of psychiatric disorders. Clinical studies (open-label and comparator with treatment in naturalistic setting) in patients with TRD have produced promising results, especially when the response rates at longer-term (one- and two-year) follow-up time points are considered. Ongoing research efforts will help determine the place of VNS in the armament of therapeutic modalities available for major depression.


Subject(s)
Depression/therapy , Electric Stimulation Therapy/methods , Electric Stimulation Therapy/trends , Vagus Nerve , Electroconvulsive Therapy/methods , Humans , Vagus Nerve/anatomy & histology
13.
Clin Exp Rheumatol ; 25(2): 312-4, 2007.
Article in English | MEDLINE | ID: mdl-17543161

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.


Subject(s)
Lymph Nodes/pathology , Lymphatic Diseases/etiology , Still's Disease, Adult-Onset/complications , Adult , Biopsy , Diagnosis, Differential , Female , Hodgkin Disease/diagnosis , Humans , Lymph Nodes/metabolism , Lymphatic Diseases/diagnosis , Lymphatic Diseases/pathology , Lymphoma, T-Cell, Cutaneous/diagnosis , Melanins/metabolism , Still's Disease, Adult-Onset/diagnosis , Still's Disease, Adult-Onset/pathology
14.
Scand J Rheumatol ; 36(2): 101-6, 2007.
Article in English | MEDLINE | ID: mdl-17476615

ABSTRACT

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.


Subject(s)
Inflammation/metabolism , Interleukin-6/blood , Leptin/blood , Spondylitis, Ankylosing/blood , Adult , Blood Sedimentation , Body Mass Index , C-Reactive Protein , Humans , Inflammation/immunology , Leptin/immunology , Male , Prospective Studies , Severity of Illness Index , Spondylitis, Ankylosing/immunology , Tumor Necrosis Factor-alpha/blood
15.
Clin Exp Rheumatol ; 25(1 Suppl 44): S18-22, 2007.
Article in English | MEDLINE | ID: mdl-17428358

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.


Subject(s)
Genetic Predisposition to Disease , HLA-A Antigens/genetics , Takayasu Arteritis/genetics , Adolescent , Adult , Angiography , Female , Gene Frequency , HLA-A Antigens/blood , HLA-B Antigens/blood , HLA-B Antigens/genetics , HLA-DR Antigens/blood , HLA-DR Antigens/genetics , HLA-DRB1 Chains , Heart Failure/complications , Heart Failure/genetics , Heart Failure/pathology , Histocompatibility Testing , Humans , Korea , Male , Middle Aged , Takayasu Arteritis/blood , Takayasu Arteritis/complications , Takayasu Arteritis/pathology
16.
Clin Exp Rheumatol ; 24(2 Suppl 41): S10-6, 2006.
Article in English | MEDLINE | ID: mdl-16859589

ABSTRACT

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.


Subject(s)
Antibodies, Antiphospholipid/blood , Autoantibodies/blood , Takayasu Arteritis/blood , Takayasu Arteritis/immunology , Adult , Antibodies, Antiphospholipid/analysis , Antibodies, Antiphospholipid/physiology , Autoantibodies/analysis , Autoantibodies/physiology , Blood Sedimentation , Case-Control Studies , Endothelium, Vascular/cytology , Endothelium, Vascular/immunology , Female , Humans , Immunoglobulin G/analysis , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin Isotypes/blood , Immunoglobulin M/analysis , Immunoglobulin M/blood , Immunoglobulin M/immunology , Male , Middle Aged , Severity of Illness Index , Takayasu Arteritis/physiopathology , Umbilical Veins/cytology , Umbilical Veins/immunology
18.
Rheumatology (Oxford) ; 45(5): 545-8, 2006 May.
Article in English | MEDLINE | ID: mdl-16352633

ABSTRACT

OBJECTIVE: To investigate serum profiles of inflammatory cytokines in patients with Takayasu's arteritis (TA) and to determine their correlations with disease activity of TA. METHODS: 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. RESULTS: 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). CONCLUSION: 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.


Subject(s)
Cytokines/blood , Takayasu Arteritis/immunology , Adult , Biomarkers/blood , Blood Sedimentation , C-Reactive Protein/metabolism , Female , Humans , Interleukin-18/blood , Interleukin-6/blood , Leukocyte Count , Male , Middle Aged , Severity of Illness Index , Takayasu Arteritis/blood
19.
Rheumatology (Oxford) ; 45(5): 600-5, 2006 May.
Article in English | MEDLINE | ID: mdl-16352637

ABSTRACT

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.


Subject(s)
Arterial Occlusive Diseases/prevention & control , Immunosuppressive Agents/therapeutic use , Takayasu Arteritis/therapy , Adolescent , Adult , Arterial Occlusive Diseases/diagnostic imaging , Arterial Occlusive Diseases/etiology , Arterial Occlusive Diseases/therapy , Drug Therapy, Combination , Female , Follow-Up Studies , Glucocorticoids/therapeutic use , Humans , Male , Middle Aged , Radiography , Recurrence , Retrospective Studies , Takayasu Arteritis/complications , Takayasu Arteritis/diagnostic imaging , Treatment Outcome , Vascular Patency
20.
Scand J Rheumatol ; 34(4): 284-92, 2005.
Article in English | MEDLINE | ID: mdl-16195161

ABSTRACT

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
Angiography/methods , Glucocorticoids/therapeutic use , Immunosuppressive Agents/therapeutic use , Methotrexate/therapeutic use , Takayasu Arteritis/diagnostic imaging , Takayasu Arteritis/drug therapy , Adolescent , Adult , Blood Sedimentation , Child , Child, Preschool , Cohort Studies , Disease Progression , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Korea , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Risk Assessment , Severity of Illness Index , Survival Rate , Takayasu Arteritis/diagnosis , Takayasu Arteritis/mortality , Treatment Outcome
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