B. Yoo

Effects of advanced glycation end products on the expression of COX-2, PGE2 and NO in human osteoarthritic chondrocytes

OBJECTIVEnAdvanced glycation end products (AGE) accumulate in articular cartilage with age. We investigated the effects of AGE in primary-cultured human OA chondrocytes.nnnMETHODSnChondrocytes were cultured with/or without AGE-bovine serum albumin (AGE-BSA) and the expression levels of inducible nitric oxide (iNOS), cyclooxygenase (COX)-2 microsomal prostaglandin E synthase-1 (mPGES-1) were evaluated using RT-PCR and western blot analysis. Prostaglandin E(2) (PGE(2)) was analysed by ELISA and nitric oxide (NO) was analysed by Griess reaction assay. Pharmacological studies to elucidate the involved pathway were executed using specific inhibitors of MAPK and receptor for AGE (RAGE).nnnRESULTSnWe found that treatment of OA chondrocytes with AGE-BSA increased COX-2, mPGES-1 and iNOS mRNA and protein, as well as elevating production of PGE(2) and NO. Pre-treatment with the MAPK inhibitors SP600125 (JNK inhibitor), SB202190 (p38 inhibitor) or PD98059 (ERK inhibitor) significantly inhibited AGE-BSA induction of COX-2 expression and production of PGE(2). In contrast, SN50, a nuclear factor-kappaB (NF-kappaB) inhibitor, had no effect on levels of COX-2 and PGE(2). SB202190 and SN50, but not SP600125 and PD98059, decreased AGE-BSA-induced production of NO. Pre-treatment with soluble receptor for AGE (sRAGE) also reduced AGE-stimulated COX-2, iNOS and PGE(2), implicating the involvement of RAGE.nnnCONCLUSIONSnThese results show that AGE may augment inflammatory responses in OA chondrocytes by increasing PGE(2) and NO levels, possibly via the MAPK pathway for PGE(2) and the NF-kappaB pathway for NO.

Behcet's disease associated with bone marrow failure in Korean patients: clinical characteristics and the association of intestinal ulceration and trisomy 8

OBJECTIVESnThe aim of this study was to determine the clinical characteristics of Behcets disease (BD) associated with bone marrow failure (BMF), classified as conditions such as myelodysplastic syndrome (MDS) or aplastic anaemia (AA), in Korea.nnnMETHODSnA retrospective analysis was made of 13 patients with BD associated with BMF (MDS 8 cases, AA 5 cases) and 66 patients with BD not associated with BMF. These patients all fulfilled the diagnostic criteria of the international BD study group.nnnRESULTSnBD patients with BMF showed significantly lower leucocyte count, haemoglobin level and platelet count when compared with patients without BMF (P < 0.001). BD patients with BMF had significantly higher serum CRP level at the time of BD diagnosis compared with patients without BMF (P = 0.03). Intestinal lesions were more frequent in BD patients with BMF than those without BMF (61.5% vs 13.6%, P = 0.001). Cytogenetic abnormality was observed in 90.9% of BD patients with BMF. Of the cytogenetic abnormalities, trisomy 8 was most common, occurring in 70% of the patients. In four patients with refractory BD associated with BMF, successful treatment of BMF by haematopoietic stem cell transplantation resulted in clinical remission of BD.nnnCONCLUSIONSnOur study indicates that intestinal ulceration is a characteristic finding in BD associated with BMF. It also suggests that cytogenetic aberration, especially trisomy 8, may play an important role in the pathogenesis of BD associated with BMF.

Serum cholesterol in idiopathic and lupus-related protein-losing enteropathy.

Abstract The characteristics of protein-losing enteropathy were evaluated in patients with systemic lupus erythematosus. Among the patients with systemic lupus erythematosus (n = 380) in a tertiary hospital, we reviewed the records of seven patients with generalized edema, hypoalbuminemia without proteinuria and positive results on 99mTc-labelled human serum albumin scintigrams. Patient characteristics and laboratory findings were compared between these seven patients and patients with lupus enteritis (n = 15) or idiopathic protein-losing enteropathy (n = 11). Compared with the lupus enteritis patients, the erythrocyte sedimentation rate and serum total cholesterol levels were significantly increased in patients with systemic lupus erythematosus–related protein-losing enteropathy. Compared with idiopathic protein-losing enteropathy patients, the level of serum total cholesterol was significantly increased, but the level of serum albumin was decreased in patients with systemic lupus erythematosus–related protein-losing enteropathy. Among patients with systemic lupus erythematosus–related protein-losing enteropathy, four patients had high serum total cholesterol levels (≥248 mg/dL) and achieved complete remission after receiving high doses of steroid treatment. However, three patients who had low serum total cholesterol levels (≤219 mg/dL) responded poorly to the steroid-only treatment, and could achieve complete remission only after 3 months of cyclophosphamide pulse treatment with concurrent corticosteroid therapy. The levels of serum total cholesterol are intriguing feature in systemic lupus erythematosus–associated protein-losing enteropathy patients.

Successful treatment of recurrent lupus enteritis with rituximab

Sir, A 23-year-old Korean woman was admitted to our hospital in August 2007 with a 4-day history of abdominal pain associated with nausea and vomiting. Three years prior to admission she had been diagnosed with systemic lupus erythematosus (SLE) based on malar rash, lymphocytopenia, positive anti-nuclear antibody, anti-Ro antibody, and anti-double-stranded (ds)DNA antibody. Antiphospholipid antibodies including lupus anticoagulant, anti-cardiolipin antibodies (immunoglobulin [Ig]M and IgG), beta2-glycoprotein I antibodies (IgM and IgG) were all negative on two repeated tests. Prior to this admission, the patient had experienced six episodes of recurrent lupus enteritis from May 2005 to July 2007. With each episode of lupus enteritis, she complained of abdominal pain with or without vomiting and diarrhea, and enhanced computed tomography (CT) scans of the abdomen showed diffuse mucosal edema and bowel wall thickening involving the small and large intestine (target-like appearance) with variable amounts of ascites (Figure 1). Laboratory findings at each admission were unremarkable except for hypocomplementemia. On each occasion, she completely recovered after intravenous (IV) treatment with high-dose steroids (methylprednisolone 1mg/kg/day) and conservative treatments including bowel rest and IV fluids. After the third episode of recurrent lupus enteritis, she received mycophenolate mofetil (MMF) until the fourth episode, and was treated with oral cyclophosphamide (CYC) for 3 months, followed by azathioprine (AZA) for 4 months. However, she experienced two more episodes of recurrent lupus enteritis until July 2007. At the seventh admission for lupus enteritis in August 2007, we decided to administer rituximab 500mg per week IV for 2 consecutive weeks in addition to high-dose steroids. The patient’s absolute CD19 count was 36.7/mm at the time of the first infusion, which decreased to 17.4/mm at 2 weeks after the first rituximab infusion. In September 2007, 3 weeks after the first infusion, the lupus enteritis recurred and high-dose methylprednisolone (2mg/kg/day IV) was administered. At four weeks after the first rituximab infusion, the patient’s CD19 count decreased to 3.1/mm. Thereafter, with gradual tapering of oral corticosteroids, no further lupus enteritis relapse occurred. At 6 months after the first infusion, the patient’s CD19 count was increased to 47.3/mm. For fear of possible relapse of lupus enteritis, she wanted repeated infusion of rituximab rather than observation without rituximab therapy. She received a second cycle of rituximab with concomitant methylprednisolone 100mg/day IV. At 7 months after this second infusion, with a CD19 count of 52.3/mm, the patient received a third cycle of rituximab with concomitant methylprednisolone. In December 2008, 15 months after discharge, the oral methylprednisolone was tapered off and no subsequent symptoms and signs of lupus flare have been reported (Figure 2). Lupus enteritis is one of the most serious complications of SLE. High doses of steroids are required and surgical intervention is indicated if extensive bowel infarction or perforation occurs. Antiphospholipid antibody syndrome can induce intestinal ischemia or infarction and cause symptoms similar to those of mesenteric vasculitis. In our patient, there was no evidence of anti-phospholipid antibodies or thrombosis, and diffuse mucosal edema with bowel wall thickening (target-like appearance) and complete reversibility after immunosuppressive treatments were strongly indicative of intestinal ischemia secondary to mesenteric vasculitis. The recommended initial treatment for lupus enteritis is high-dose parenteral steroids together with complete bowel rest. However, relapse is not uncommon, even in patients who show a good initial response to this treatment. Recently, a case of severe relapsing lupus enteritis treated successfully with a combination of CYC and rituximab was reported. This patient remained free of relapse for 2 years after treatment with two cycles of intra-venous (IV) methylprednisolone 100mg rituximab 500mg IV and CYC 500mg IV. However, the use of single-agent rituximab in lupus enteritis has not been reported. Rituximab is a chimeric monoclonal antibody directed against the CD20 molecule present on B lymphocytes. Several reports have described the use of rituximab to successfully treat refractory lupus Correspondence to: Yong-Gil Kim, Division of Rheumatology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, 388–1 Pungnap-dong, Songpa-gu, Seoul 138–736, Korea. E-mail: bestmd2000@amc.seoul.kr Received 9 April 2009; accepted 4 June 2009

Systemic lupus erythematosus complicated by acquired von Willebrand’s syndrome

Haematological abnormalities are common in systemic lupus erythematosus (SLE). In some cases of acquired von Willebrand syndrome (AvWS), von Willebrand disease (vWD) is associated with autoimmune or lymphoproliferative disorders. In this study, we describe a 36-year-old woman with SLE and AvWS. The patient was referred to our hospital because of easy bruisability and recurrent vaginal bleeding. She had no history of bleeding tendency and no family history of bleeding diathesis, but she had a history of recurrent arthralgia, photosensitivity and sicca symptoms. Tests for antinuclear, anti–double stranded DNA, anticardiolipin and anti–β2-glycoprotein I antibodies were all positive. Analysis of haemostatic parameters showed complete absence of von Willebrand factor ristocetin cofactor (vWF:Rco), von Willebrand antigen (vWF:Ag) and ristocetin-induced platelet aggregation (RIPA). Electrophoretic analysis of plasma showed a complete absence of high–molecular weight vWF multimer. The presence of antibody to vWF was detected by enzyme linked immunosorbent assay (ELISA). Treatment with corticosteroids improved SLE symptoms and corrected bleeding diasthesis. Also, the multimeric patterns of vWF became normalised and anti–vWF antibody disappeared. These findings indicated that this patient had SLE associated with AvWS, which was ameliorated by corticosteroid treatment.

Arrhythmogenic potential develops rapidly at graft reperfusion before the start of hypotension during living-donor liver transplantation

Background Detailed profiles of acute hypothermia and electrocardiographic (ECG) manifestations of arrhythmogenicity were examined to analyze acute hypothermia and ventricular arrhythmogenic potential immediately after portal vein unclamping (PVU) in living-donor liver transplantation (LT). Methods We retrospectively analyzed electronically archived medical records (n = 148) of beat-to-beat ECG, arterial pressure waveforms, and blood temperature (BT) from Swan-Ganz catheters in patients undergoing living-donor LT. The ECG data analyzed were selected from the start of BT drop to the initiation of systolic hypotension after PVU. Results On reperfusion, acute hypothermia of < 34℃, < 33℃ and < 32℃ developed in 75.0%, 37.2% and 11.5% of patients, respectively. BT decreased from 35.0℃ ± 0.8℃ to 33.3℃ ± 1.0℃ (range 35.8℃–30.5℃). The median time to nadir of BT was 10 s after PVU. Difference in BT (ΔBT) was weakly correlated with graft-recipient weight ratio (GRWR; r = 0.22, P = 0.008). Compared to baseline, arrhythmogenicity indices such as corrected QT (QTc), Tp-e (T wave peak to end) interval, and Tp-e/QTc ratio were prolonged (P < 0.001 each). ST height decreased and T amplitude increased (P < 0.001 each). However, no correlation was found between ΔBT and arrhythmogenic indices. Conclusions In living-donor LT, regardless of extent of BT drop, ventricular arrhythmogenic potential developed immediately after PVU prior to occurrence of systolic hypotension.

Lupus enteritis: clinical characteristics and predictive factors for recurrence.

Objectives To compare the clinical characteristics of lupus enteritis (LE) and non-enteric lupus (non-LE) patients and identify predictors of LE recurrence. Methods We retrospectively reviewed the medical records of 62 systemic lupus erythematosus (SLE) patients in a tertiary hospital who experienced enteric symptoms and underwent abdominal computed tomography scanning between January 1997 and December 2013. We compared the clinical characteristics between LE and non-LE patients and between recurrent LE and non-recurrent LE cases. Results Out of 62 SLE patients with enteric symptoms, 46 cases (74%) were compatible with LE based on computed tomography findings. The C4 level was decreased in the LE group compared with the non-LE group (9.0u2009±u20095.6 vs. 12.3u2009±u20096.2, pu2009=u20090.032). Recurrence of LE was observed in 14 patients (28%). Initial involvement at the colon (79% vs. 41%, pu2009=u20090.026) and bladder with/without the ureter was more common in the recurrent group (57% vs. 25%, pu2009=u20090.048). By multivariate analysis, the hazard ratios of variables associated with recurrence were 4.689 for colon involvement (95% confidence interval: 1.245–17.659, pu2009=u20090.0220] and 5.468 for cystitis with/without ureteritis (95% confidence interval: 1.629–18.360, pu2009=u20090.006). Conclusion Colon and urinary tract involvement in LE patients may be associated with the recurrence of LE.

Factors associated with acute gout attacks in normouricaemic gout patients receiving allopurinol: a retrospective study

Objective: To identify factors associated with acute gout attacks in normouricaemic gout patients receiving allopurinol. Methods: We reviewed the medical records of 860 patients with chronic gout who were treated with allopurinol at a single tertiary hospital between 2003 and 2009. Of these, 135 patients had serum urate concentrations ≤ 360 μmol/L (6 mg/dL). Patients whose serum urate concentrations exceeded 360 μmol/L (6 mg/dL) at least once during follow-up were excluded. Patients who experienced at least one acute attack during follow-up, despite normouricaemia [≤ 360 μmol/L (6 mg/dL)], were classified as the Attack group (n = 51). The others were classified as the Non-attack group (n = 84). Results: The gout disease duration was significantly longer in the Attack group than in the Non-attack group (p = 0.036). The presence of tophi and multiple joint involvement were associated with acute attacks in normouricaemic gout patients. Multivariate analysis showed that both the presence of tophi [odds ratio (OR) 4.16, 95% confidence interval (CI) 1.41–12.23, p = 0.010] and the number of involved joints (OR 1.51, 95% CI 1.05–2.17, p = 0.028) were independently associated with acute attacks in normouricaemic gout patients receiving allopurinol. Conclusion: The presence of tophi and multiple joint involvement were associated with acute attacks in normouricaemic gout patients receiving allopurinol.

Pulsed Radiofrequency Ablation Under Ultrasound Guidance for Huge Neuroma

Amputation neuroma can cause very serious, intractable pain. Many treatment modalities are suggested for painful neuroma. Pharmacologic treatment shows a limited effect on eliminating the pain, and surgical treatment has a high recurrence rate. We applied pulsed radiofrequency treatment at the neuroma stalk under ultrasonography guidance. The long-term outcome was very successful, prompting us to report this case.

AB0689 Extravascular manifestations of takayasu arteritis: historical cohort study in korea

Background Takayasu arteritis (TAK) is systemic disease characterised by large vessel involvement. Although the vascular characteristics of TAK are well characterised, there is no well-organised study demonstrating the extravascular manifestations of TAK. Objectives To evaluate the characteristics of extravascular manifestations of TAK, and to identify the association between vascular and extravascular manifestations of TAK. Methods TAK patients from two independent cohorts who fulfilled the 1990 ACR classification and encoded M314 according to ICD-10 code between January 2012 and October 2017 were included in the study. Characteristics of the patients were retrospectively collected from the electronic dataset. A radiologist reviewed CT scans of all included patients to evaluate the pattern of vascular involvement and presence of sacroiliitis. Clinical findings including uveitis, skin lesion, oral ulcer, arthritis, and inflammatory bowel disease (IBD) were reviewed. Logistic regression analysis was performed to evaluate the association between vascular and extravascular manifestation. Results A total of 268 TAK patients were included. Mean age at diagnosis was 41.2±14.2 years and 236 (88.1%) were female. The most commonly involved vessel was common carotid artery (176 [65.7%]), and the most common type of vascular involvement was type V (120 [44.8%]). Extravascular manifestation of TAK was observed in 51 (19.0%) patients (table 1). The most common extravascular manifestation was arthritis (axial arthritis [sacroiliitis] [7.1%] and/or peripheral arthritis [6.0%]) (11.9%) followed by recurrent aphthous stomatitis (8.6%) and IBD (2.6%). In multivariable logistic regression analysis, the following factors were significantly associated with presence of arthritis (axial and/or peripheral arthritis): type IIB vascular involvement (adjusted OR 2.956, 95%u2009CI 1.337–6.537, p=0.007) and erythrocyte sedimentation rate (ESR) (adjusted OR 1.014 95%u2009CI 1.003–1.025, p=0.012).Abstract AB0689 – Table 1 Extravascular manifestations of Takayasu arteritis n=268 Any extravascular manifestation 51 (19.0%) Arthritis (axial arthritis [sacroiliitis] and/or peripheral arthritis) 32 (11.9%) Recurrent aphthous stomatitis 23 (8.6%) Inflammatory bowel disease 7 (2.6%) Erythema nodosum 4 (1.5%) Uveitis 2 (0.7%) Conclusions Extravascular manifestations of TAK are not rare and observed in up to one-fifth of patients. The most common extravascular manifestation was arthritis including sacroiliitis (11.9%). Type IIb vascular involvement pattern and high ESR were significantly associated with arthritis in TAK. Acknowledgements None Disclosure of Interest None declared