A 22-year-old woman visited our clinic with a history of radiofrequency volumetric reduction for bilateral masseter muscles at a local medical clinic. Six days after the radiofrequency procedure, she noticed a facial asymmetry during smiling. Physical examination revealed immobility of the mouth drawing upward and laterally on the left. Routine nerve conduction studies and needle electromyography (EMG) in facial muscles did not suggest electrodiagnostic abnormalities. We assumed that the cause of facial asymmetry could be due to an injury of zygomaticus muscles, however, since defining the muscles through surface anatomy was difficult and it was not possible to identify the muscles with conventional electromyographic methods. Sono-guided needle EMG for zygomaticus muscle revealed spontaneous activities at rest and small amplitude motor unit potentials with reduced recruitment patterns on volition. Sono-guided needle EMG may be an optimal approach in focal facial nerve branch injury for the specific localization of the injury lesion.
Ultrasonography-guided; Zygomaticus; Needle electromyography
Macrophage activation syndrome (MAS) is one of the serious complications of juvenile rheumatoid arthritis (JRA) and recently, cyclosporine A has been found to be effective in patients with corticosteroid-resistant MAS. A 29-yr-old male was admitted with high fever and jaundice for one month. He was diagnosed as juvenile arthritis 16 yr ago. Physical and laboratory results showed hepatosplenomegaly, high fever, pancytopenia and impaired liver and renal function tests, elevated triglyceride and serum ferritin levels. Bone marrow biopsy showed hyperplasia of histiocytes with active hemophagocytosis. He was diagnosed as MAS associated with juvenile rheumatoid arthritis and managed with high-dose corticosteroids initially, but clinical symptoms and laboratory findings did not improve immediately. Finally, he completely recovered after treatment with cyclosporine A (3 mg/kg/day).
Macrophage activation syndrome; Arthritis, Juvenile Rheumatoid; Cyclosporine
The primary aim of this study was to investigate the acute impact of methylphenidate (MPH) on sleep parameters in attention-deficit/hyperactivity disorder (ADHD) children. The second aim was to investigate the different effects of intermediate- and longacting MPH on sleep parameters. The third aim was to test the different effects of dose and age on sleep parameters.
Ninety-three ADHD children were enrolled and randomized to two different MPH preparations. Baseline and daily sleep diaries were evaluated for four weeks after taking medication. Weekday and weekend bedtimes, wake-up times, sleep latencies and total sleep times were compared by weeks.
After taking MPH, there was a significant delay in bedtimes and a significant reduction of total sleep time (TST) both on weekdays and at weekends. There was also a significant delay in wake-up time on weekdays. However, the difference was applied to younger age group children only. There was no difference in changes of TST between metadate-CD and OROS-MPH. There also was no difference in changes of TST with different doses of MPH.
MPH had negative impacts on sleep among young ADHD children, but different preparations and doses did not affect the result.
ADHD; Children; Methylphenidate; OROS-MPH; Metadate-CD
To compare a newly developed minimally-invasive method for percutaneous transforaminal epidural injection (INJ group) with the existing method for lumbar epidural catheterization (CATH group).
Through anatomical review of experimental rats, the cephalic one fourth of the neural foramen was selected as the target point for drug delivery. After the rats had undergone lumbar epidural catheterization, lidocaine, and 1% methylene blue were injected through the unilateral or bilateral L5/6 neural foramen in the INJ group, and through an epidural catheter in the CATH group. Measurement of body weight and the mechanical allodynia test before and after injection of lidocaine, and fine dissection after injection were performed.
Results of the mechanical allodynia test of 1.0% lidocaine 50 µl injection in the CATH group were statistically similar to those of 0.5% lidocaine 100 µl injection in the INJ group. The results of 2.0% lidocaine 50 µl injection in the CATH group were statistically similar to those of 1.0% lidocaine 100 µl injection in the INJ group. After dissection, only one distal partial spinal nerve was stained by methylene blue 50 µl through the transforaminal pathway. However, the dorsal root ganglion, nerve root, and adjacent hemi-partial spinal cord were stained by methylene blue 100 µl through the transforaminal pathway.
The percutaneous transforaminal epidural injection is practical, easy, and safe, and, in particular, does not cause significant pain compared to the existing lumbar epidural catheterization. We expect this method to be effective in an animal study showing that drug delivery to the spinal epidural space is necessary.
Epidural catheterization; Transforaminal; Animal study; Pain; Lidocaine
Fibromyalgia (FM) is characterized by chronic widespread pain with a low pain threshold. The aim of this study was to compare two criteria for the diagnosis and assessment of FM and to analyze the correlation and agreement between the 1990 and 2010 American College of Rheumatology (ACR) preliminary diagnostic criteria for FM.
We studied 98 patients who had already been diagnosed as having FM using the 1990 criteria or 2010 preliminary criteria. Tender point examination, FM impact questionnaire (FIQ) and pain visual analog scale (VAS) were obtained. According to the preliminary criteria, FM was quantified as WPI (widespread pain index) and the SS scale (symptom severity) and the two criteria were compared.
Among 98 patients, 78.6% of the patients were diagnosed with the 1990 ACR criteria and 93.9% of the patients were diagnosed with the ACR preliminary diagnostic criteria, and there was also significant agreement between the two criteria (P < 0.01). There was a correlation with the WPI and the tender point, with the SS and the FIQ, and with the sum of the WPI and SS and the FIQ.
The ACR preliminary diagnostic criteria for FM were in agreement with the 1990 ACR criteria during the disease course. The preliminary criteria were the more sensitive method than the 1990 criteria. In addition, the 2010 criteria might have advantages since it is easy to assess the physical and psychological symptoms and can be quantified. Therefore, the ACR preliminary diagnostic criteria for FM could be used more conveniently for clinical diagnosis and follow up evaluation after starting management of FM.
fibromyalgia; 1990 criteria; 2010 preliminary criteria
We herein investigated the role of the STAT signaling cascade in the production of pro-inflammatory cytokines and cisplatin ototoxicity. A significant hearing impairment caused by cisplatin injection was observed in Balb/c (wild type, WT) and STAT4−/−, but not in STAT6−/− mice. Moreover, the expression levels of the protein and mRNA of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, were markedly increased in the serum and cochlea of WT and STAT4−/−, but not STAT6−/− mice. Organotypic culture revealed that the shape of stereocilia bundles and arrays of sensory hair cell layers in the organ of Corti from STAT6−/− mice were intact after treatment with cisplatin, whereas those from WT and STAT4−/− mice were highly distorted and disarrayed after the treatment. Cisplatin induced the phosphorylation of STAT6 in HEI-OC1 auditory cells, and the knockdown of STAT6 by STAT6-specific siRNA significantly protected HEI-OC1 auditory cells from cisplatin-induced cell death and inhibited pro-inflammatory cytokine production. We further demonstrated that IL-4 and IL-13 induced by cisplatin modulated the phosphorylation of STAT6 by binding with IL-4 receptor alpha and IL-13Rα1. These findings suggest that STAT6 signaling plays a pivotal role in cisplatin-mediated pro-inflammatory cytokine production and ototoxicity.
cisplatin; ototoxicity; STAT; inflammation; apoptosis
Rectal carcinoid tumors, at diagnosis, are as small as 10 mm or less in about 80% of patients. These tumors are generally removed by endoscopic resection. The aim of this study was to compare treatment efficacy and safety between endoscopic submucosal resection with band ligation (ESMR-L) and conventional polypectomy.
Between January 2005 and September 2010, a total of 88 patients, who visited at Busan Paik Hospital and Kosin University Gospel Hospital for endoscopic resection of rectal carcinoid, were reviewed, retrospectively.
Thirty-three cases were treated by ESMR-L, and 55 cases by conventional polypectomy. There were no significant difference in the size of tumor between ESMR-L group and polypectomy group (6.02±2.36 vs. 6.49±3.24 mm, p=0.474). The rate of positive resection margin was significantly lower in ESMR-L group (2/33, 6.1%) than in polypectomy group (19/55, 34.5%; p=0.002). The rate of positive vertical resection margin, among others, was markedly lower in ESMR-L group (1/33, 3.0%) compared to polypectomy group (19/55, 34.5%; p<0.001).
ESMR-L, rather than conventional polypectomy, is a useful treatment option for removal of rectal carcinoid tumors less than 10 mm in diameter.
Rectal carcinoid tumor; Polypectomy; Band ligation
The reappearance rates of hepatitis C virus (HCV) RNA after a sustained virological response (SVR) have been reported to be 1-2%. We investigated the reappearance rate of HCV RNA after SVR in chronic hepatitis C (CHC) patients treated with pegylated interferon (PEG-IFN) and ribavirin.
In total, 292 CHC patients who achieved an SVR after PEG-IFN and ribavirin treatment were included. They were treated with subcutaneous injections of either PEG-IFN-α 2a or 2b plus ribavirin orally. Liver function tests and qualitative HCV RNA assays were performed every 6 months during the follow-up period after an SVR.
Among the 292 patients, 224 (genotype 1, 92; genotype non-1, 132) were followed up for more than 6 months after SVR. These 224 patients were aged 48.1±11.5 years (mean±SD), and 129 of them were male. The median follow-up duration was 18 months (range 6-60 months). The reappearance rate of HCV RNA during follow-up was 0%. Two patients who achieved an SVR developed hepatocellular carcinoma during the follow-up period.
An SVR was maintained in all CHC patients treated with PEG-IFN plus ribavirin during a median follow-up of 18 months. However, a screening test for hepatocellular carcinoma is needed for patients with an SVR.
Durability; Sustained virological response; Chronic hepatitis C; Pegylated interferon; Ribavirin
Macrophage migration inhibitory factor (MIF) is one of key regulators in acute and chronic immune-inflammatory conditions including rheumatoid arthritis (RA). We examined the effect of MIF on osteoclastogenesis, which is known to play a crucial role in bone destruction in RA.
The concentration of MIF and receptor activator of nuclear factor-κB ligand (RANKL) in the synovial fluid was measured by ELISA. MIF-induced RANKL expression of RA synovial fibroblasts was determined by real-time PCR and western blot. Osteoclastogenesis was analyzed in culture of human peripheral blood mononuclear cells (PBMC) with MIF. Osteoclastogenesis was also determined after co-cultures of rhMIF-stimulated RA synovial fibroblasts with human PBMC.
Synovial fluid MIF concentration in RA patients was significantly higher than in osteoarthritis (OA) patients. The concentration of RANKL correlated with that of MIF in RA synovial fluids (r = 0.6, P < 0.001). MIF stimulated the expression of RANKL mRNA and protein in RA synovial fibroblasts, which was partially reduced by blocking of interleukin (IL)-1β. Osteoclasts were differentiated from PBMC cultures with MIF and M-CSF, even without RANKL. Osteoclastogenesis was increased after co-culture of MIF-stimulated RA synovial fibroblasts with PBMC and this effect was diminished by RANKL neutralization. Blocking of PI3 kinase, p38 MAP kinase, JAK-2, NF-κB, and AP-1 also led to a marked reduction in RANKL expression and osteoclastogenesis.
The interactions among MIF, synovial fibroblasts, osteoclasts, RANKL, and IL-1β have a close connection in osteoclastogenesis and they could be a potential gateway leading to new therapeutic approaches in treating bone destruction in RA.
This study was undertaken to identify the intracellular signaling pathway involved in induction of macrophage migration inhibitory factor (MIF) in human rheumatoid arthritis (RA) synovial fibroblasts.
Human RA synovial fibroblasts were treated with concanavalin A (ConA), various cytokines, and inhibitors of signal transduction molecules. The production of MIF by synovial fibroblasts was measured in culture supernatants by ELISA. The expression of MIF mRNA was determined using reverse transcriptase polymerase chain reaction (RT-PCR) and real-time PCR. Phosphorylation of p38 mitogen-activated protein (MAP) kinase in synovial fibroblasts was confirmed using Western blotting. The expression of MIF and p38 MAP kinase in RA synovium was determined using dual immunohistochemistry.
The production of MIF by RA synovial fibroblasts increased in a dose-dependent manner after ConA stimulation. MIF was also induced by interferon-γ, CD40 ligand, interleukin-15, interleukin-1β, tumor necrosis factor-α, and transforming growth factor-β. The production of MIF by RA synovial fibroblasts was significantly reduced after inhibition of p38 MAP kinase. The expression of MIF and p38 MAP kinase was upregulated in the RA synovium compared with the osteoarthritis synovium.
These results suggest that MIF production was induced through a p38 MAP-kinase-dependent pathway in RA synovial fibroblasts.
Macrophage, migration-inhibitory factors; Arthritis rheumatoid; Synovial fibroblast; p38 mitogen-activated protein kinases
The aim of this study was to analyze the relationship between serum pro-hepcidin concentration and the anemia profiles of rheumatoid arthritis (RA) and to estimate the pro-hepcidin could reflect the disease activity of RA. RA disease activities were measured using Disease Activity Score 28 (DAS28), tender/swollen joint counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Anemia profiles such as hemoglobin, iron, total iron binding capacity (TIBC), ferritin, and transferrin levels were measured. Serum concentration of pro-hepcidin, the prohormone of hepcidin, was measured using enzyme-linked immunosorbent assay (ELISA). Mean concentration of serum pro-hepcidin was 237.6±67.9 ng/mL in 40 RA patients. The pro-hepcidin concentration was correlated with rheumatoid factor, CRP, ESR, and DAS28. There was a significant correlation between pro-hepcidin with tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. The pro-hepcidin concentration was significantly higher in the patients with active RA (DAS28>5.1) than those with inactive to moderate RA (DAS28≤5.1). However, the pro-hepcidin concentration did not correlate with the anemia profiles except hemoglobin level. There was no difference of pro-hepcidin concentration between the patients with anemia of chronic disease and those without. In conclusion, serum concentration of pro-hepcidin reflects the disease activity, regardless of the anemia states in RA patients, thus it may be another potential marker for disease activity of RA.
Arthritis, Rheumatoid; Anemia; Hepcidin; Prohepcidin
Limy bile is a relatively rare condition in which a radiopaque material is visible in the gallbladder, extending rarely into the bile duct, on plain radiography. Acute cholangitis or cholecystitis caused by limy bile is a very rare condition. There are no definite treatment guidelines for limy bile, but in most cases with cholangitis or cholecystitis, laparoscopic cholecystectomy has been the preferred treatment. We report a case of limy bile with biliary symptoms that was treated only with an endoscopic procedure.
Limy bile; Cholangitis, Cholecystitis; Endoscopic transpapillary gallbladder drainage
Cryptococcal infection is a rare, yet well recognized complication of systemic lupus erythematosus (SLE). We present a case of mesenteric and retroperitoneal cryptococcal lymphadenitis resulting in the obstruction of the stomach and proximal duodenum in a patient suffering from SLE, while recently she did not receive any immunosuppressive treatment. A 42-yr-old woman was admitted due to high fever and diffuse abdominal pain for three weeks. Abdominal computed tomography (CT) scan showed multiple conglomerated lymphadenopathies in the retroperitoneum and the mesentery resulting in luminal narrowing of the third portion of the duodenum. Cryptococcal lymphadenitis was proven by needle biopsy and she was treated with intravenous liposomal amphotericin B, followed by oral fluconazole. After fourteen-month antifungal therapies, the clinical symptoms and follow-up images improved. This case emphasize that the intrinsic immunological defects of SLE may be directly responsible for the predisposition to fungal infections.
Mesenteric Lymphadenitis; Cryptococcus neoformans; Lupus Erythematosus, Systemic
Inflammatory mediators have been recognized as being important in the pathogenesis of rheumatoid arthritis (RA). Interleukin (IL)-17 is an important regulator of immune and inflammatory responses, including the induction of proinflammatory cytokines and osteoclastic bone resorption. Evidence for the expression and proinflammatory activity of IL-17 has been demonstrated in RA synovium and in animal models of RA. Although some cytokines (IL-15 and IL-23) have been reported to regulate IL-17 production, the intracellular signaling pathways that regulate IL-17 production remain unknown. In the present study, we investigated the role of the phosphoinositide 3-kinase (PI3K)/Akt pathway in the regulation of IL-17 production in RA. Peripheral blood mononuclear cells (PBMC) from patients with RA (n = 24) were separated, then stimulated with various agents including anti-CD3, anti-CD28, phytohemagglutinin (PHA) and several inflammatory cytokines and chemokines. IL-17 levels were determined by sandwich enzyme-linked immunosorbent assay and reverse transcription–polymerase chain reaction. The production of IL-17 was significantly increased in cells treated with anti-CD3 antibody with or without anti-CD28 and PHA (P < 0.05). Among tested cytokines and chemokines, IL-15, monocyte chemoattractant protein-1 and IL-6 upregulated IL-17 production (P < 0.05), whereas tumor necrosis factor-α, IL-1β, IL-18 or transforming growth factor-β did not. IL-17 was also detected in the PBMC of patients with osteoarthritis, but their expression levels were much lower than those of RA PBMC. Anti-CD3 antibody activated the PI3K/Akt pathway; activation of this pathway resulted in a pronounced augmentation of nuclear factor κB (NF-κB) DNA-binding activity. IL-17 production by activated RA PBMC is completely or partly blocked in the presence of the NF-κB inhibitor pyrrolidine dithiocarbamate and the PI3K/Akt inhibitor wortmannin and LY294002, respectively. However, inhibition of activator protein-1 and extracellular signal-regulated kinase 1/2 did not affect IL-17 production. These results suggest that signal transduction pathways dependent on PI3K/Akt and NF-κB are involved in the overproduction of the key inflammatory cytokine IL-17 in RA.
interleukin-17; nuclear factor κB; PI3K/Akt pathway; peripheral blood mononuclear cells; rheumatoid arthritis
Various genetic and environmental factors appear to be involved in systemic lupus erythematosus (SLE). Epstein–Barr virus (EBV) is among the environmental factors that are suspected of predisposing to SLE, based on the characteristics of EBV itself and on sequence homologies between autoantigens and EBV antigens. In addition, higher titers of anti-EBV antibodies and increased EBV seroconversion rates have been observed in SLE patients as compared with healthy control individuals. Serologic responses do not directly reflect EBV status within the body. Clarification of the precise status of EBV infection in SLE patients would help to improve our understanding of the role played by EBV in this disease. In the present study we determined EBV types in SLE patients (n = 66) and normal control individual (n = 63) by direct PCR analysis of mouthwash samples. We also compared EBV load in blood between SLE patients (n = 24) and healthy control individuals (n = 29) using semiquantitative PCR assay. The number of infections and EBV type distribution were similar between adult SLE patients and healthy control individuals (98.5% versus 94%). Interestingly, the EBV burden in peripheral blood mononuclear cells (PBMCs) was over 15-fold greater in SLE patients than in healthy control individuals (mean ± standard deviation: 463 ± 570 EBV genome copies/3 μg PBMC DNA versus 30 ± 29 EBV genome copies/3 μg PBMC DNA; P = 0.001), suggesting that EBV infection is abnormally regulated in SLE. The abnormally increased proportion of EBV-infected B cells in the SLE patients may contribute to enhanced autoantibody production in this disease.
Epstein–Barr virus; Epstein–Barr virus type; systemic lupus erythematosus; virus burden
Hanwoo (Korean cattle), which originated from natural crossbreeding between taurine and zebu cattle, migrated to the Korean peninsula through North China. Hanwoo were raised as draft animals until the 1970s without the introduction of foreign germplasm. Since 1979, Hanwoo has been bred as beef cattle. Genetic variation was analyzed by whole-genome deep resequencing of a Hanwoo bull. The Hanwoo genome was compared to that of two other breeds, Black Angus and Holstein, and genes within regions of homozygosity were investigated to elucidate the genetic and genomic characteristics of Hanwoo.
The Hanwoo bull genome was sequenced to 45.6-fold coverage using the ABI SOLiD system. In total, 4.7 million single-nucleotide polymorphisms and 0.4 million small indels were identified by comparison with the Btau4.0 reference assembly. Of the total number of SNPs and indels, 58% and 87%, respectively, were novel. The overall genotype concordance between the SNPs and BovineSNP50 BeadChip data was 96.4%. Of 1.6 million genetic differences in Hanwoo, approximately 25,000 non-synonymous SNPs, splice-site variants, and coding indels (NS/SS/Is) were detected in 8,360 genes. Among 1,045 genes containing reliable specific NS/SS/Is in Hanwoo, 109 genes contained more than one novel damaging NS/SS/I. Of the genes containing NS/SS/Is, 610 genes were assigned as trait-associated genes. Moreover, 16, 78, and 51 regions of homozygosity (ROHs) were detected in Hanwoo, Black Angus, and Holstein, respectively. ‘Regulation of actin filament length’ was revealed as a significant gene ontology term and 25 trait-associated genes for meat quality and disease resistance were found in 753 genes that resided in the ROHs of Hanwoo. In Hanwoo, 43 genes were located in common ROHs between whole-genome resequencing and SNP chips in BTA2, 10, and 13 coincided with quantitative trait loci for meat fat traits. In addition, the common ROHs in BTA2 and 16 were in agreement between Hanwoo and Black Angus.
We identified 4.7 million SNPs and 0.4 million small indels by whole-genome resequencing of a Hanwoo bull. Approximately 25,000 non-synonymous SNPs, splice-site variants, and coding indels (NS/SS/Is) were detected in 8,360 genes. Additionally, we found 25 trait-associated genes for meat quality and disease resistance among 753 genes that resided in the ROHs of Hanwoo. These findings will provide useful genomic information for identifying genes or casual mutations associated with economically important traits in cattle.
Hanwoo; Resequencing; NS/SS/I; ROH
The receptor for advanced glycation end-products (RAGE) has been implicated in the pathogenesis of arthritis. We conducted this study to determine the effect of interleukin (IL)-17 on the expression and production of RAGE in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). The role of nuclear factor-κB (NF-κB) activator 1 (Act1) in IL-17-induced RAGE expression in RA-FLS was also evaluated.
RAGE expression in synovial tissues was assessed by immunohistochemical staining. RAGE mRNA production was determined by real-time polymerase chain reaction. Act-1 short hairpin RNA (shRNA) was produced and treated to evaluate the role of Act-1 on RAGE production.
RAGE, IL-17, and Act-1 expression increased in RA synovium compared to osteoarthritis synovium. RAGE expression and production increased by IL-17 and IL-1β (*P <0.05 vs. untreated cells) treatment but not by tumor necrosis factor (TNF)-α in RA-FLS. The combined stimuli of both IL-17 and IL-1β significantly increased RAGE production compared to a single stimulus with IL-17 or IL-1β alone (P <0.05 vs. 10 ng/ml IL-17). Act-1 shRNA added to the RA-FLS culture supernatant completely suppressed the enhanced production of RAGE induced by IL-17.
RAGE was overexpressed in RA synovial tissues, and RAGE production was stimulated by IL-17 and IL-1β. Act-1 contributed to the stimulatory effect of IL-17 on RAGE production, suggesting a possible inhibitory target for RA treatment.