Efficacy and safety of enavogliflozin vs. dapagliflozin as add-on therapy in patients with type 2 diabetes mellitus based on renal function: a pooled analysis of two randomized controlled trials.

BACKGROUND: We assessed the efficacy and safety of enavogliflozin (0.3 mg), a newly developed SGLT-2 inhibitor, in patients with type 2 diabetes mellitus based on kidney function via pooled analysis of two 24-week, randomized, double-blind phase III trials. METHODS: Data from 470 patients were included (enavogliflozin: 0.3 mg/day, n = 235; dapagliflozin: 10 mg/day, n = 235). The subjects were classified by mildly reduced (60 ≤ eGFR < 90 mL/min/1.73 m², n = 247) or normal eGFR (≥ 90 mL/min/1.73 m², n = 223). RESULTS: In the mildly reduced eGFR group, enavogliflozin significantly reduced the adjusted mean change of HbA1c and fasting plasma glucose levels at week 24 compared to dapagliflozin (- 0.94% vs. -0.77%, P = 0.0196). Enavogliflozin exhibited a more pronounced glucose-lowering effect by HbA1c when combined with dipeptidyl peptidase-4 inhibitors than that observed in their absence. Enavogliflozin showed potent blood glucose-lowering effects regardless of renal function. Conversely, dapagliflozin showed a significant decrease in the glucose-lowering efficacy as the renal function decreased. Enavogliflozin showed a higher urinary glucose excretion rate in both groups. The homeostatic model assessment showed that enavogliflozin markedly decreased the insulin resistance. The blood pressure, weight loss, or homeostasis model assessment of beta-cell function values did not differ significantly between enavogliflozin and dapagliflozin. Adverse events were similar between both drugs. CONCLUSIONS: The glucose-lowering efficacy of enavogliflozin is superior to that of dapagliflozin in patients with type 2 diabetes mellitus with mild renal function impairment; this is attributed to its potent urinary glucose excretion-promoting ability. The emergence of new and potent SGLT-2 inhibitors is considered an attractive option for patients with inadequate glycemic control and decreased renal function. TRIAL REGISTRATION: Not applicable (pooled analysis).

Efficacy and safety of enavogliflozin, a novel SGLT2 inhibitor, in Korean people with type 2 diabetes: A 24-week, multicentre, randomized, double-blind, placebo-controlled, phase III trial.

AIMS: To evaluate the efficacy and safety of a novel sodium-glucose cotransporter 2 inhibitor, enavogliflozin 0.3 mg monotherapy, in Korean people with type 2 diabetes mellitus (T2DM) inadequately controlled with diet and exercise. MATERIALS AND METHODS: This study was a randomized, double-blind, placebo-controlled trial conducted in 23 hospitals. Individuals with haemoglobin A1c (HbA1c) of 7.0%-10.0% after at least 8 weeks of diet and exercise modification were randomized to receive enavogliflozin 0.3 mg (n = 83) or placebo (n = 84) for 24 weeks. The primary outcome was a change in HbA1c at week 24 from baseline. Secondary outcomes included the proportion of participants achieving HbA1c <7.0%, change in fasting glucose, body weight and lipid levels. Adverse events were investigated throughout the study. RESULTS: At week 24, the placebo-adjusted mean change in HbA1c from baseline in the enavogliflozin group was -0.99% (95% confidence interval -1.24%, -0.74%). The proportions of patients achieving HbA1c <7.0% (71% vs. 24%) at week 24 was significantly higher in the enavogliflozin group (p < .0001). Placebo-adjusted mean changes in fasting plasma glucose (-40.1 mg/dl) and body weight (-2.5 kg) at week 24 were statistically significant (p < .0001). In addition, a significant decrease in blood pressure, low-density lipoprotein cholesterol, triglyceride, and homeostasis model assessment of insulin resistance were observed, along with a significant increase in high-density lipoprotein cholesterol. No significant increase in treatment-related adverse events was observed for enavogliflozin. CONCLUSIONS: Monotherapy with enavogliflozin 0.3 mg improved glycaemic control in people with T2DM. Enavogliflozin therapy also exerted beneficial effects on body weight, blood pressure and lipid profile.

Safety and Effectiveness of Transforaminal Epiduroscopic Laser Ablation in Single Level Disc Disease: A Case-Control Study.

BACKGROUND: The non-operative treatment of herniated intervertebral discs has long been a fundamental challenge. A novel technique of laser ablation to ablate the nucleus pulposus under a transforaminal epiduroscope (TELA system, Lutronics, Seoul, Republic of Korea) was recently developed. OBJECTIVE: The purpose of this study was to evaluate the safety and effectiveness of transforaminal epiduroscopic laser ablation (TELA) for selective ablation of the nucleus pulposus in single-level disc disease. STUDY DESIGN: Prospective case control studySETTING: Multicenter studyMETHODS: This study included a group of 56 patients who underwent transforaminal epiduroscopic laser ablation (TELA) and 56 patients who underwent selective transforaminal epidural block (STEB) for single-level disc disease. Visual analog scale (VAS), Oswestry Disability Index (ODI), and SF-12 were assessed at admission and at 1, 3, 6, and 12 months postoperatively. RESULTS: The mean VAS of back pain was lower for the TELA group than for the STEB group 12 months postoperative (P < 0.05). The mean ODI was lower in the TELA group than in the STEB group at 12 months postoperatively (P < 0.05). There were no major complications related to the TELA and STEB procedures. LIMITATIONS: The primary limitation is a small sample size. The control group was created from a database which was prospectively collected in a different time line. CONCLUSIONS: The TELA procedure is superior to the STEB procedure in terms of patients reporting less pain and better quality of life over a year. TELA may be a reasonable alternative to conventional interventions or open surgery in single-level disc disease. KEY WORDS: Laser-assisted spinal endoscopy, disc decompression, Nd:YAG laser, laser ablation, intervertebral disc disease, lumbar spine.

The SNP rs3128965 of HLA-DPB1 as a genetic marker of the AERD phenotype.

BACKGROUND: Two common clinical syndromes of acetylsalicylic acid (aspirin) hypersensitivity, aspirin-exacerbated respiratory disease (AERD) and aspirin-exacerbated cutaneous disease (AECD), were subjected to a genome-wide association study to identify strong genetic markers for aspirin hypersensitivity in a Korean population. METHODS: A comparison of SNP genotype frequencies on an Affymetrix Genome-Wide Human SNP array of 179 AERD patients and 1989 healthy normal control subjects (NC) revealed SNPs on chromosome 6 that were associated with AERD, but not AECD. To validate the association, we enrolled a second cohort comprising AERD (n = 264), NC (n = 238) and disease-control (aspirin tolerant asthma; ATA, n = 387) groups. RESULTS: The minor genotype frequency (AG or AA) of a particular SNP, rs3128965, in the HLA-DPB1 region was higher in the AERD group compared to the ATA or NC group (P = 0.001, P = 0.002, in a co-dominant analysis model, respectively). Comparison of rs3128965 alleles with the clinical features of asthmatics revealed that patients harboring the A allele had increased bronchial hyperresponsiveness to inhaled aspirin and methacholine, and higher 15-HETE levels, than those without the A allele (P = 0.039, 0.037, and 0.004, respectively). CONCLUSIONS: This implies the potential of rs3128965 as a genetic marker for diagnosis and prediction of the AERD phenotype.

Lumbar disc rehydration postimplantation of a posterior dynamic stabilization system.

Biological attempts at disc regeneration are promising; however, disc degeneration is closely related to other predisposing factors such as alteration of disc height, intradiscal pressure, load distribution, and motion. The restoration of the physiological status of the affected spinal segment is thus necessary prior to attempts at disc regeneration. Dynamic stabilization systems now offer the potential of a mechanical approach to intervertebral disc regeneration. The authors used decompression and placement of the BioFlex dynamic stabilization device to treat a young male patient with disc degeneration. This patient underwent follow-up, and he was found to gradually improve both neurologically and radiographically. On MR imaging performed 1 year postoperatively, he had an increase in disc height and disc rehydration. This case and the concept of disc rehydration are presented in this paper.

Biomechanical comparison of single-level posterior versus transforaminal lumbar interbody fusions with bilateral pedicle screw fixation: segmental stability and the effects on adjacent motion segments.

OBJECT: Both posterior lumbar interbody fusion (PLIF) and transforaminal lumbar interbody fusion (TLIF) have been frequently undertaken for lumbar arthrodesis. These procedures use different approaches and cage designs, each of which could affect spine stability, even after the addition of posterior pedicle screw fixation. The objectives of this biomechanical study were to compare PLIF and TLIF, each accompanied by bilateral pedicle screw fixation, with regard to the stability of the fused and adjacent segments. METHODS: Fourteen human L2-S2 cadaveric spine specimens were tested for 6 different modes of motion: flexion, extension, right and left lateral bending, and right and left axial rotation using a load control protocol (LCP). The LCP for each mode of motion utilized moments up to 8.0 Nm at a rate of 0.5 Nm/second with the application of a constant compression follower preload of 400 N. All 14 specimens were tested in the intact state. The specimens were then divided equally into PLIF and TLIF conditions. In the PLIF Group, a bilateral L4-5 partial facetectomy was followed by discectomy and a single-level fusion procedure. In the TLIF Group, a unilateral L4-5 complete facetectomy was performed (and followed by the discectomy and single-level fusion procedure). In the TLIF Group, the implants were initially positioned inside the disc space posteriorly (TLIF-P) and the specimens were tested; the implants were then positioned anteriorly (TLIF-A) and the specimens were retested. All specimens were evaluated at the reconstructed and adjacent segments for range of motion (ROM) and at the adjacent segments for intradiscal pressure (IDP), and laminar strain. RESULTS: At the reconstructed segment, both the PLIF and the TLIF specimens had significantly lower ROMs compared with those for the intact state (p < 0.05). For lateral bending, the PLIF resulted in a marked decrease in ROM that was statistically significantly greater than that found after TLIF (p < 0.05). In flexion-extension and rotation, the PLIF Group also had less ROM, however, unlike the difference in lateral bending ROM, these differences in ROM values were not statistically significant. Variations in the position of the implants within the disc space were not associated with any significant differences in ROM values (p = 0.43). Analyses of ROM at the adjacent levels L2-3, L3-4, and L5-S1 showed that ROM was increased to some degree in all directions. When compared with that of intact specimens, the ROMs were increased to a statistically significant degree at all adjacent segments in flexion-extension loads (p < 0.05); however, the differences in values among the various operative procedures were not statistically significant. The IDP and facet contact force for the adjacent L3-4 and L5-S1 levels were also increased, but these values were not statistically significantly increased from those for the intact spine (p > 0.05). CONCLUSIONS: Regarding stability, PLIF provides a higher immediate stability compared with that of TLIF, especially in lateral bending. Based on our findings, however, PLIF and TLIF, each with posterolateral fusions, have similar biomechanical properties regarding ROM, IDP, and laminar strain at the adjacent segments.

Biomechanical analysis of the range of motion after placement of a two-level cervical ProDisc-C versus hybrid construct.

STUDY DESIGN: The study design was that of an in vitro human cadaveric biomechanical analysis. OBJECTIVES: The objective of this study was the biomechanical analysis of the range of motion (ROM) of a 2-level intact spine control versus total, then operative- and adjacent-segment ROM after (1) 2-level ProDisc-C placement (PP), (2) anterior cervical discectomy and fusions (ACDFs), and (3) hybrid constructs of both. Follower load and multidirectional testing were performed in each instance. SUMMARY OF BACKGROUND DATA: With in vivo cervical arthroplasties gaining in popularity, limited biomechanical data are available, which highlight changes in the adjacent-level biomechanics after multilevel procedures. METHODS: Biomechanical testing for ROM was performed using 7 cadaveric C4-T1 spine specimens. Moments up to 2 Nm with a 100 N follower load were applied in flexion/extension (F/E), right and left lateral bending (LB), and right and left axial rotation (AR). Specimens were tested in the intact state and then with a combination of ProDisc-C arthroplasty and ACDF at C5-C6 and C6-C7. RESULTS: In the 2-level PP group, the increase in ROM in F/E, LB, and AR of C4-T1 occurs due to an increased ROM at the operative level. The ROM of the level adjacent to the operative levels showed no significant change, except at C4-C5 in LB. For the latter level, the ROM of C4-C5 in each direction showed increases for each parameter. In the 2-level fusion C5-C6 and C6-C7 fusion (FF) group, the ROM in F/E, LB, and AR of C4-T1 was decreased because of a decrease in ROM primarily at the fused levels, and the ROM of adjacent levels was increased. In the ProDisc-C/Fusion (PF) and Fusion/ProDisc-C (FP) groups undergoing placements of a 1-level ProDisc-C/1-level fusion with cage and plate, both groups showed no significant ROM change of C4-T1 when compared with the control and no significant change at adjacent levels, with the exception of C4-C5 in LB. CONCLUSION: (1) Two-level ACDFs decrease whereas 2-level PPs increase the entire C4-T1 ROM. (2) ACDF/ProDisc-C hybrid operations do not alter the C4-T1 ROM. (3) For the ACDF/ProDisc-C hybrid operative groups, the combined ROM of the operative levels showed no significant difference when compared with that of the intact spine. (4) Regarding adjacent-level ROM, a 2-level ACDF increases ROM, but 2-level ProDisc-C and hybrid ACDF/PPs do not show significant change except for LB at C4-C5. (5) When the segmental distribution of C4-T1 ROM is plotted as the percentage of total motion, it demonstrates that for PF and FP groups, the combined ROM of the C5-C6 and C6-C7 operative levels are similar to that of the intact spine in EF and LB. For the PP group, the combined ROM of the operative levels increased, whereas the combined ROM for the FF group is decreased. The decrease or increase of the adjacent C4-C5 or C7-T1 level ROM compensates for the operative levels.

IL-13 Gene Polymorphisms are Associated With Rhinosinusitis and Eosinophilic Inflammation in Aspirin Intolerant Asthma.

PURPOSE: Aspirin-intolerant asthma (AIA) is characterized by moderate to severe asthma that is aggravated by aspirin or other non-steroidal anti-inflammatory drugs. Affected patients frequently have chronic rhinosinusitis and nasal polyposis due to persistent upper and lower airway inflammation with marked eosinophilia. IL-13 plays a crucial role in the development of allergic asthma by inducing airway eosinophilia and hyper-reactivity and it has been correlated with an increased eosinophil count. METHODS: Two promoter polymorphisms of the IL-13 gene (-1510 A>C and -1055C>T) and one coding nonsynonymus Arg110Gln (110G>A) polymorphism were genotyped using primer extension methods in 162 patients with AIA, 301 patients with aspirin-tolerant asthma (ATA), and 430 normal healthy controls (NC). RESULTS: There was no significant difference in the genotype, allele, and haplotype frequencies of the three polymorphisms among the three groups. AIA patients with the AA genotype -1510A>C (P=0.012) and CC genotype -1055C>T (P<0.001) had a significantly higher frequency of rhinosinusitis, as compared to those with the minor alleles of these two single nucleotide polymorphisms. AIA patients with the GG genotype had a higher peripheral eosinophil count (P=0.025) and a higher serum eotaxin-1 level (P=0.044), as compared to patients with the AA genotype IL-13 Arg110Gln (110G>A). CONCLUSIONS: These findings suggest that the IL-13 polymorphisms at -1510A>C and 1055C>T are associated with the development of rhinosinusitis in AIA patients. IL-13 Arg110Gln may be associated with an increased eosinophil count and eotaxin-1 level and could increase eosinophilic inflammation in the upper and lower airways of patients with AIA.

Association of interleukin-18 gene polymorphisms with hepatitis B virus clearance.

The outcome of hepatitis B virus (HBV) infection can be affected by host immune factors. Interleukin-18 (IL-18) was originally discovered as an interferon-gamma-inducing factor and plays a critical role in immune response. We assessed the association between the clearance of HBV infection and single-nucleotide polymorphisms (SNPs) in the IL-18 gene. Between March 2002 and December 2004, a total of 1,050 Korean subjects were enrolled in the study and divided into two groups: (1) the HBV spontaneous recovery group (n = 320) and (2) the chronic HBV carrier group (n = 730). We analyzed SNPs at four polymorphic sites in the IL-18 gene at positions -667G>T, -148G>C, +8925C>G, and +13925A>C. We observed that the subjects bearing the IL-18 -148C allele [odds ratio (OR), 0.25; confidence interval (CI), 0.09-0.68; P = 0.01], the +8925G allele (OR, 0.36; CI, 0.15-0.88; P = 0.02), and the +13925C allele (OR, 0.25; CI, 0.13-0.82; P = 0.01) were significantly associated with HBV clearance in a recessive model. This study indicates that the -148C, +8925G, and +13925C alleles of the IL-18 gene are likely associated with HBV clearance in a Korean population.

The BioFlex System as a Dynamic Stabilization Device : Does It Preserve Lumbar Motion?

OBJECTIVE: This study examines whether functional motion is present at one or more years after Bioflex System placement. BioFlex System is a flexible rod system which has been used to preserve motion at the area of implantation. There has not been a scientific study showing how much motion is preserved after implantation. METHODS: A total of 12 consecutive patients underwent posterior dynamic stabilization using the BioFlex System. Six patients were treated using a L3-4-5 construct and other six patients using a L4-5-S1 construct. Follow-up ranged from 12 to 33 months and standing neutral lateral, extension, flexion and posteroanterior (PA) radiographs were obtained at 3, 6, 9, and 12 months and at more than 12 months postoperatively. Range of motion (ROM), whole lumbar lordosis, and ROMs of motion segments from L2 to S1 were determined. RESULTS: Patients with a L3-4-5 construct demonstrated a decrease in mean ROM for whole lumbar decreased from 40.08 to 30.77. Mean ROM for L3-4 (6.12 to 2.20) and L4-5 (6.55 to 1.67) also decreased after one year. Patients with a L4-5-S1 construct demonstrated L4-5 (8.75 to 2.70) and L5-S1 (9.97 to 3.25) decrease of mean ROM at one year postoperatively. Lumbar lordosis was preserved at both L3-4-5 and L4-5-S1 constructs. Clinical results showed significant improvements in both study groups. CONCLUSION: The present study provides preliminary information regarding the BioFlex motion preservation system. We conclude that the BioFlex System preserves functional motion to some degree at instrumented levels. However, although total lumbar lordosis was preserved, ROMs at implantation segments were lower than preoperative values.

Imaging correlation of the degree of degenerative L4-5 spondylolisthesis with the corresponding amount of facet fluid.

OBJECT: The aim of this study was to correlate the degree of L4-5 spondylolisthesis on plain flexion-extension radiographs with the corresponding amount of L4-5 facet fluid visible on MR images. METHODS: Patients underwent evaluation at the Neurosurgical Spine Clinics of Stanford University Medical Center and National Health Insurance Medical Center (Goyang, South Korea) between January 2006 and December 2007. Only patients who were diagnosed with L4-5 degenerative spondylolisthesis (DS) and who had both lumbosacral flexion-extension radiographs and MR images available for review were eligible for this study. Each patient's dynamic motion index (DMI) was measured using the lateral lumbosacral plain radiograph and was the percentage of the degree of anterior slippage seen on flexion versus that seen on extension. Axial T2-weighted MR images of the L4-5 facet joints obtained in each patient was analyzed for the amount of facet fluid, using the image showing the widest portion of the facets. The facet fluid index was calculated from the ratio of the sum of the amounts of facet fluid found in the right plus left facets over the sum of the average widths of the right plus left facet joints. RESULTS: Fifty-four patients with L4-5 DS were included in this study. Of these 54 patients, facet fluid was noted on MR images in 29 patients (53.7%), and their mean DMI was 6.349 +/- 2.726. Patients who did not have facet fluid on MR imaging had a mean DMI of 1.542 +/- 0.820; this difference was statistically significant (p < 0.001). There was a positive linear association between the facet fluid index and the DMI in the group of patients who exhibited facet fluid on MR images (Pearson correlation coefficient 0.560, p < 0.01). In the subgroup of 29 patients with L4-5 DS who showed facet fluid on MR images, flexion-extension plain radiographs in 10 (34.5%) showed marked anterolisthesis, while the corresponding MR images did not. CONCLUSIONS: There is a linear correlation between the degree of segmental motion seen on flexion-extension plain radiography in patients with DS at L4-5 and the amount of L4-5 facet fluid on MR images. If L4-5 facet fluid in patients with DS is seen on MR images, a corresponding anterolisthesis on weight-bearing flexion-extension lateral radiographs should be anticipated. Obtaining plain radiographs will aid in the diagnosis of anterolisthesis caused by an L4-5 hypermobile segment, which may not always be evident on MR images obtained in supine patients.

Change of lumbar motion after multi-level posterior dynamic stabilization with bioflex system : 1 year follow up.

OBJECTIVE: This study examined the change of range of motion (ROM) at the segments within the dynamic posterior stabilization, segments above and below the system, the clinical course and analyzed the factors influencing them. METHODS: This study included a consecutive 27 patients who underwent one-level to three-level dynamic stabilization with Bioflex system at our institute. All of these patients with degenerative disc disease underwent decompressive laminectomy with/without discectomy and dynamic stabilization with Bioflex system at the laminectomy level without fusion. Visual analogue scale (VAS) scores for back and leg pain, whole lumbar lordosis (from L1 to S1), ROMs from preoperative, immediate postoperative, 1.5, 3, 6, 12 months at whole lumbar (from L1 to S1), each instrumented levels, and one segment above and below this instrumentation were evaluated. RESULTS: VAS scores for leg and back pain decreased significantly throughout the whole study period. Whole lumbar lordosis remained within preoperative range, ROM of whole lumbar and instrumented levels showed a significant decrease. ROM of one level upper and lower to the instrumentation increased, but statistically invalid. There were also 5 cases of complications related with the fixation system. CONCLUSION: Bioflex posterior dynamic stabilization system supports operation-induced unstable, destroyed segments and assists in physiological motion and stabilization at the instrumented level, decrease back and leg pain, maintain preoperative lumbar lordotic angle and reduce ROM of whole lumbar and instrumented segments. Prevention of adjacent segment degeneration and complication rates are something to be reconsidered through longer follow up period.

Polymethylmethacrylate-augmented screw fixation for stabilization of the osteoporotic spine : a three-year follow-up of 37 patients.

OBJECTIVE: The purpose of this study was to determine the efficacy, radiological findings, clinical outcomes and complications in patients with lumbar stenosis and osteoporosis after the use of polymethylmethacrylate (PMMA) augmentation of a cannulated pedicle screw. METHODS: Thirty-seven patients with degenerative spinal stenosis and osteoporosis (T-score < -2.5) underwent lumbar fusion using the Dream Technology Pedicle Screw (DTPS, Dream Spine Total Solutions, Dream STS, Seoul, Korea) between 2005 and 2007. The clinical outcomes were evaluated by using the visual analog scale (VAS) and the Prolo scale. Radiologic findings were documented through computed tomography (CT) and plain films. RESULTS: Thirty-seven patients were evaluated and included, 2 males and 35 females with an average bone mineral density (BMD) of 0.47g/cm(2). The average age of the patients was 68.7 (range, 57-88). The preoperative VAS for low back and leg pain (7.87 +/- 0.95 and 8.82 +/- 0.83) were higher as compared with postoperative VAS (2.30 +/- 1.61 and 1.42 +/- 0.73) with statistical significance (p = 0.006, p = 0.003). According to the Prolo scale, 11, 22, one and three patients were in excellent, good, fair and poor conditions, respectively. The average amount of the injected cement per one cannulated screw was 1.83 +/- 0.11 mL. CONCLUSION: The results show favorable outcome both clinically and radiographically for 37 patients who underwent lumbar fusion using DTPS and PMMA. Based on the results, the use of this surgical method can be a safe and effective option for the operation on the osteoporotic spine.

Association of CRTH2 gene polymorphisms with the required dose of antihistamines in patients with chronic urticaria.

INTRODUCTION: Chronic urticaria (CU), defined as the recurring incidence of wheals with or without angioedema for more than 6 weeks, is a common disorder associated with mast cell activation, degranulation, and histamine release. Considering the association between the CRTH2 gene and mast cells, we investigated the association of this gene polymorphism with the CU phenotype and antihistamine drug requirement in patients with CU. MATERIALS & METHODS: Two groups consisting of 384 patients with CU and 231 patients as normal controls (NCs) were enrolled from the Department of Allergy and Rheumatology, Ajou University Hospital, Suwon, Korea. Two polymorphisms of the CRTH2 gene, -466T>C and -129C>A were genotyped using primer extension methods. RESULTS: No significant differences were detected in the genotype and allele frequencies of the two CRTH2 polymorphisms between the CU and NC groups, and no significant associations were observed with clinical parameters, such as atopy status, serum total IgE, prevalence of autoantibodies and duration of CU. However, CU patients with homozygous TT genotypes had significantly higher dose requirements of antihistamines to control the CU symptoms (164.56 +/- 115.62 vs 137.38 +/- 90.15 loratadine equivalents, mg/week) than those with the CT and CC genotypes (p = 0.025). The luciferase activity was significantly enhanced in the construct containing CRTH2 466C compared with the -466T-containing construct (p < 0.001). Co-transfection experiments with GATA-3 (300 ng) and the -466T and -466C CRTH2 alleles revealed that the CRTH2 -466T allele produced a greater increase in induction of luciferase activity than the -466C allele (p < 0.001). CONCLUSION: The CRTH2 -466T>C gene polymorphism may not affect on the phenotype of CU, but contributes to the required dose of antihistamines in patients with CU.

Association of three sets of high-affinity IgE receptor (FcepsilonR1) polymorphisms with aspirin-intolerant asthma.

BACKGROUND AND OBJECTIVE: The high-affinity IgE receptor comprises a tetramer of the ligand-binding alpha chain, a signal-augmenting beta chain, and a signal-transducing gamma chain dimer on mast cells. We hypothesized that the three subsets of the FCER1 gene may play a role in the development of the aspirin-intolerant asthma (AIA) phenotype and analyzed these genetic polymorphisms in association with clinical parameters in AIA patients. SUBJECTS AND METHODS: Six polymorphisms of FCER1 (FCERIA-344C>T, FCER1A-95T>C, MS4A2-109T>C, MS4A2 E237G, FCER1G-237A>G, FCER1G-54G>T) were genotyped in 126 AIA patients compared to 177 patients with aspirin-tolerant asthma (ATA) and 222 normal health controls (NC). RESULTS: A significant difference in the genotype frequencies of FCER1G-237A>G was detected between AIA and ATA patients (p<0.05) both in co-dominant and recessive analysis models, whereas no significant relationships were identified between the frequencies of the other five single-nucleotide polymorphisms and AIA, ATA, and NC subjects. In addition, AIA patients carrying the homozygous AA genotype of FCER1G-237A>G exhibited significantly higher total serum IgE levels than did those with the GG/AG genotype (p=0.012). AIA patients expressing the CT/TT genotype at FCERIA-344C>T showed a higher prevalence of serum IgE specific to Staphylococcal enterotoxin A than did those with the CC genotype (p=0.008). CONCLUSION: The FCER1G-237A>G and FCERIA-344C>T polymorphisms may contribute to the development of AIA in a Korean population.

Association of four-locus gene interaction with aspirin-intolerant asthma in Korean asthmatics.

INTRODUCTION: Aspirin-intolerant asthma (AIA), a major clinical presentation of aspirin hypersensitivity, affects 10% of adult asthmatics. The genetic risk factors involved in the susceptibility to AIA have recently been investigated, but multilocus single-nucleotide polymorphisms (SNPs) associated with this susceptibility has not been evaluated. METHODS: We examined 246 asthmatic patients: 94 having aspirin intolerance and 152 having aspirin tolerance. We selected 23 SNPs of 13 candidate genes and genotyped each SNP using a primer extension method. Multilocus genetic interactions were examined using multifactor dimensionality reduction (MDR) to test all multilocus SNP combinations to identify a useful SNP set for predicting the AIA phenotype. RESULTS: We identified the best model using the MDR method, which consisted of a four-locus gene-gene interaction with 65.16% balanced accuracy and a cross-validation consistency of 70% in predicting AIA disease risk among asthmatic patients. This model included four SNPs such as B2ADR 46A>G, CCR3-520T>G, CysLTR1-634C>T, and FCER1B-109T>C. DISCUSSION: These results suggest that a multilocus SNP acts in combination to influence the susceptibility to aspirin intolerance in asthmatics and could be a useful genetic marker for the diagnosis of AIA.

Synovial cyst in the cervical region causing severe myelopathy.

The authors describe a case of an 80-year-old man with a gradual weakness of the lower extremities not linked to any known traumatic episode over the 2 weeks before admission. CT scan and MRI of the spine revealed a cystic formation, measuring about 1 cm in diameter, at C7-T1 at the left posterolateral site at the level of the articular facet. During surgery, the mass appeared to be in the ligamentum flavum at the level of the articular facet and was in contact with the dura mater. After the removal of the mass, there was an immediate and significant improvement of the patient's symptoms. Histopathologic examination showed the cyst to be composed of nonspecific degenerative fibrous tissue with mild inflammatory change and confirmed the cyst as a synovial cyst. Synovial cyst in the cervical region is a very rare lesion causing myelopathy. Surgical removal of the cyst and decompression of the spinal cord results in good neurological recovery.