Salivary gland ultrasonography findings are associated with clinical, histological, and serologic features of Sjögren's syndrome.

OBJECTIVE: Salivary gland ultrasonography (SGUS) has been applied in the diagnosis of Sjögren's syndrome (SS). The aim of this study is to investigate the association of SGUS findings with clinical, histological, and serologic features of SS. METHODS: A total of 104 patients with suspected SS underwent SGUS for evaluation of salivary gland involvement. Patients with primary SS were determined according to the classification criteria for SS. The parenchymal inhomogeneity of bilateral parotid and submandibular glands was graded from 0 (homogeneity) to 4 (gross inhomogeneity). Receiver operating characteristic curve analysis was performed to compare the diagnostic performance of different SGUS scoring methods. Clinical and serologic features were compared between groups classified by SGUS score. The association between SGUS and these features of SS was explored by multivariable linear regression analysis. RESULTS: Study participants were predominantly women (96.2%) and had a mean age of 54.1 years. Eighty-seven patients and 88 patients with primary SS were identified based on AECG criteria and ACR/EULAR classification criteria for SS, respectively. Among the different scoring methods, the sum of the grades of four salivary glands (range 0-16) had the best diagnostic performance, with sensitivity of 77.3% and specificity of 87.5% (cutoff value, 7) for distinguishing primary SS from sicca non-SS. SGUS score was associated with focus score in labial salivary gland biopsy (ß = 0.240, p = 0.033) and anti-Ro/SSA serology (ß = 0.283, p = 0.016) and inversely associated with unstimulated whole salivary flow (ß = -0.298, p = 0.011). CONCLUSION: Ultrasonography of major salivary glands is associated with histopathology of minor salivary glands, serology of SS, and salivary gland function.

Effect of alcohol consumption and smoking on disease damage in systemic lupus erythematosus: data from the Korean Lupus Network (KORNET) registry.

Background We assessed correlations of smoking habits and alcohol consumption with disease activity or damage in patients with systemic lupus erythematosus (SLE). Methods A total of 505 patients with SLE were enrolled in the Korean Lupus Network (KORNET) SLE registry from January 2014 to January 2016. Disease activity and organ damage were measured by the SLE Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index, respectively. Multivariate logistic regression analysis was used to analyze associations with cutaneous lesions. Results There were no differences in SLEDAI-2K and SLICC/ACR damage indices according to either smoking status or alcohol consumption. More frequent cutaneous damage was observed in current alcohol drinkers compared with non-current alcohol drinkers ( p = 0.020). Cutaneous damage was significantly associated with alcohol consumption (odds ratio (OR) 4.048, 95% confidence interval (CI) 1.251-12.102, p = 0.020). Both low (1-5 glasses/week) and high (≥6 glasses/week) amounts of alcohol consumption had a significant impact on cutaneous damage compared with the absence of current alcohol consumption ( p = 0.033 and p = 0.027, respectively). Pairwise comparison of alcohol consumption and smoking status with cutaneous damage showed that only alcohol consumption was significantly associated with the presence of cutaneous damage, compared with non-current alcohol consumption and non-current smoking (OR 3.513, 95% CI 1.130-10.920, p =0.030). Conclusions Current alcohol consumption, but not smoking, might influence the development of cutaneous damage in patients with SLE.

Pain, xerostomia, and younger age are major determinants of fatigue in Korean patients with primary Sjögren's syndrome: a cohort study.

OBJECTIVES: Fatigue is a common clinical manifestation in patients with primary Sjögren's syndrome (pSS). The aims of this study were to investigate the association between fatigue severity and other clinical characteristics in pSS patients and to determine the factors contributing to fatigue. METHOD: We analysed 257 participants from the Korean Initiative of pSS (KISS), a prospective pSS cohort. Fatigue was assessed according to the fatigue domain of the European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient-Reported Index (ESSPRI). Health-related quality of life (HRQoL) was evaluated using the EuroQol-5 dimensions (EQ-5D) questionnaire. Multiple linear regression analysis was used to estimate the effect of each variable on fatigue severity. RESULTS: The median total ESSPRI score was 5 [interquartile range (IQR) 4-6]. Thirty-four per cent of patients reported a fatigue score > 5. Younger and premenopausal patients presented with more fatigue (p = 0.013 and p < 0.001, respectively). Higher Xerostomia Inventory (XI) scale (p < 0.001) and Ocular Surface Dryness Index (OSDI) (p < 0.001) scores were observed in patients with a fatigue score > 5. Pain, xerostomia, and age were determined to be significantly associated with fatigue severity after adjusting for depression/anxiety, OSDI score, and the presence of fibromyalgia using a multivariate general linear model. The ESSPRI fatigue score was correlated with the EQ-5D by time trade-off (TTO) values and visual analogue scale (VAS) scores. CONCLUSIONS: In Korean patients with pSS, younger age, xerostomia, and pain were correlated significantly with fatigue, and fatigue was associated with HRQoL.

Urine ß2-microglobulin is associated with clinical disease activity and renal involvement in female patients with systemic lupus erythematosus.

OBJECTIVE: We investigated the association of serum and urine ß2-microglobulin (ß2MG) with renal involvement and clinical disease activity in systemic lupus erythematosus (SLE). METHODS: Sixty-four female patients with SLE were enrolled. We assessed SLE disease activity (SLEDAI)-2K and measured serum and urine ß2MG levels, as well as complement (C3 and C4) and anti-dsDNA levels. According to the SLEDAI scores, two groups were categorized: low (0-5 of SLEDAI) and high (6-19 of SLEDAI) disease activity groups. The presence of renal involvement was determined by renal SLEDAI score. Statistical analysis was performed using Spearman's correlation analysis, Mann-Whitney U test, multivariate regression analysis, and logistic regression analysis. RESULTS: Urine ß2MG levels were significantly different between low and high SLEDAI groups (p = 0.001), but not for serum ß2MG levels (p = 0.579). Patients with renal involvement showed higher urine ß2MG levels compared to those without renal involvement (p < 0.001), but again there was not a difference in serum ß2MG levels (p = 0.228). Urine ß2MG was closely associated with SLEDAI (r = 0.363, p = 0.003), renal SLEDAI (r = 0.479, p < 0.001), urine protein/Cr (r = 0.416, p = 0.001), and ESR (r = 0.347, p = 0.006), but not serum ß2MG (r = 0.245, p = 0.051). Urine ß2MG level was identified as a surrogate for renal involvement (p = 0.009, OR = 1.017, 95% CI 1.004-1.030) and overall disease activity (p = 0.009, OR = 1.020, 95% CI 1.005-1.036). CONCLUSIONS: We demonstrated that urine ß2MG levels are associated with renal involvement and overall clinical disease activity in SLE.

Arterial stiffness and proinflammatory cytokines in fibromyalgia syndrome.

OBJECTIVES: We assessed arterial stiffness and inflammatory cytokine profiles in fibromyalgia syndrome (FMS) patients and analysed the association between them. METHODS: Twenty-seven FMS patients and 29 age-matched premenopausal healthy controls were enrolled in this study. Arterial stiffness was assessed by pulse wave velocity (PWV) and augmentation index (AIx) from pulse waveform analysis. Levels of serum interleukin-1ß (IL-1ß), IL-6, IL-8, and vascular endothelial growth factor (VEGF) were measured by enzyme-linked immunosorbent assay, and a colorimetric assay was used for measurement of serum nitric oxide (NO) metabolites (nitrate and nitrite, NOx) level. Statistical analyses included the Mann-Whitney U-test and Spearman's correlation coefficient analysis. RESULTS: Higher AIx and AIx@HR75 (aortic AIx at a heart rate of 75 beats/min) were noted in FMS compared to those in the controls after adjustment using covariants (p(adj)=0.023 and p(adj)<0.001). However, there were no differences between the three regional PWVs of the two groups at the aorta-femoral, femoral-dorsalis, and aorta-radialis arteries (p(adj)>0.05 for all). FMS subjects had significantly higher serum IL-8 levels than did the healthy controls (327.9±588.7 vs. 76.4±90.5, p(adj)=0.041). However, there were no significant differences in serum IL-1ß, IL-6, VEGF, or NOx levels between the FMS patients and the controls (p(adj)>0.05 of all). Serum IL-8 level did not correlate with PWV and AIx in FMS patients. CONCLUSIONS: This study demonstrates higher AIx and IL-8 levels in FMS subjects compared to those of the controls. However, arterial stiffness including AIx in FMS was not determined by the serum IL-8 level.

The Severe Cognitive Impairment Rating Scale--an instrument for the assessment of cognition in moderate to severe dementia patients.

BACKGROUND/AIMS: This study aimed to develop a brief, reliable and valid test for cognitive function of severely demented patients. METHODS: We constructed the Severe Cognitive Impairment Rating Scale, which consisted of 11 items covering memory, language, visuospatial function, frontal function and orientation, and investigated its reliability and validity on 267 subjects [normal: 65, very mild Alzheimer's disease (AD): 42, mild AD: 58, moderate AD: 36, severe AD: 44, profound AD: 22]. RESULTS: The internal consistency obtained by Cronbach's coefficient alpha was 0.93. The interrater reliability and test-retest reliability in the moderately to severely impaired subjects with an MMSE score of

Cervical spine involvement in longstanding ankylosing spondylitis.

OBJECTIVE: To investigate the degree of ossification and the frequency of ankylosis between the atlas and the dens of the axis in patients with longstanding ankylosing spondylitis (AS), to assess radiological involvement of the cervical spine, and to determine their correlations with structural severity and clinical variables, including neurological abnormalities. METHODS: In 61 AS patients with disease duration over 7 years, the findings of conventional radiographs were graded by the Bath Ankylosing Spondylitis Radiology Index (BASRI), and the ossification levels between the atlas and the dens and the severity of zygapophyseal (ZA) joint lesions were scored using multislice CT. Neurological examinations and somatosensory evoked potentials (SSEP) were performed by neurologists. RESULTS: According to the BASRI, 50 patients (82.0%) had radiological changes of the cervical spine > or = score 1. Thirty-seven patients (60.6%) revealed a certain extent of the atlantodental ossification, and the presence of partial or complete atlantodental ankylosis was seen over 30% of the patients. The BASRI-cervical spine score and the atlantodental ossification levels correlated with disease duration. ZA involvement was observed in 49 patients (80.3%), including 23 with ZA fusion (37.7%). Although 4 of 11 patients with atlantoaxial subluxation showed abnormal SSEP none had significant neurological complications. This might be attributed in part to atlantodental ankylosis and ZA fusion. Finally, ossifications of the anterior and posterior longitudinal ligaments were found 26.2 and 29.5%, respectively. CONCLUSION: Cervical spine involvement and atlantodental ossification or ankylosis appear to be common in patients with longstanding AS, and to be particularly more severe in patients with a longer disease duration.

Lumbosacral spine and pelvic inlet changes associated with pelvic organ prolapse.

OBJECTIVE: To determine the association between advanced pelvic organ prolapse and changes in lumbar lordosis and/or pelvic inlet orientation. METHODS: Lateral lumbosacral spine/pelvic x-rays were taken of women with grade 2 or greater uterovaginal prolapse and women with grade 1 or less prolapse standing in their usual upright posture. The angles of lumbar lordosis and the pelvic inlet were measured by a radiologist who was masked to the pelvic examination findings. RESULTS: Twenty women with prolapse were matched with 20 women without significant prolapse. There were no significant differences in the mean (+/- standard deviation [SDI) age (55.3 +/- 9.0 years compared with 53.4 +/- 9.5 years), body mass index (BMI) (28.9 +/- 5.6 compared with 28.4 +/- 5.2), gravidity (5.6 +/- 3.5 compared with 5.0 +/- 2.7), and vaginal parity (4.65 +/- 3.3 compared with 4.5 +/- 2.9) between the prolapse and nonprolapse groups, respectively. All participants were vaginally parous. The mean lumbar lordotic angle in women with pelvic organ prolapse (32.0 degrees +/- 9.8 degrees) was significantly lower than that of controls (42.4 degrees +/- 10.9 degrees) (P < .003). The mean angle of the pelvic inlet in women with pelvic organ prolapse (37.5 degrees +/- 7.0 degrees) was significantly larger than that of controls (29.5 degrees +/- 7.3 degrees) (P < .001). The differences in the mean angles of lumbar lordosis and the pelvic inlet, between the case and control groups, remained significant after multivariable logistic regression was performed. CONCLUSION: Women with advanced uterovaginal prolapse have less lumbar lordosis and a pelvic inlet that is oriented less vertically than women without prolapse.

Association between HLA-DR B1 and clinical features of adult onset Still's disease in Korea.

OBJECTIVE: To determine whether HLA-DR alleles are associated with the development and clinical features of Adult Onset Still's Disease (AOSD) in Korea. METHODS: Forty-seven patients (41 women, 6 men, mean age at diagnosis 31.6 yr) meeting Yamaguchi's criteria for AOSD and 144 healthy controls were enrolled in this study. The patients with AOSD were subdivided into groups according to their chronicity: monocyclic systemic, polycyclic systemic, and chronic destructive type, and were furthermore classified as non-articular, oligoarticular or polyarticular types (having arthritis involving 5 or more joints) according to the extent of articular involvement. HLA-DRB1 genotypes were assessed by PCR-SSOP. RESULTS: Patients with AOSD had more frequent DRB1*12 (p = 0.028, relative risk (RR) = 2.27, 95% confidence interval (CI): 1.08-4.80) and DRB1*15 (p = 0.013, RR = 2.16, 95% CI: 1.17-4.00). They had less frequent DRB1*04 (p = 0.006, RR = 0.35, 95% CI: 0.16-0.75) compared to controls. DRB1*14 (p = 0.011, RR = 3.80, 95% CI: 1.27-11.31) were associated with the monocyclic systemic type. CONCLUSION: Korean AOSD patients had more frequent DRB1*12 and DRB1*15, and less frequent HLA-DRB1*04. The patients with the monocyclic systemic type had more frequent DRB1*14 alleles. This study suggests that Korean AOSD patients have distinct immunogenetic profiles, and that it would be valuable to assess the relationships between HLA-DRB1 genes and polymorphisms of proinflammatory cytokines in the pathogenesis of AOSD.

Validation of the classification criteria commonly used in Korea and a modified set of preliminary criteria for Behçet's disease: a multi-center study.

OBJECTIVE: Recently we have proposed a modified set of criteria to settle the questions raised regarding the International Study Group (ISG) criteria for Behçet's disease (BD). The aim of the present study was to validate the two pre-existing criteria sets commonly used in Korea, the ISG criteria and the criteria of the Behçet's Disease Research Committee of Japan (Japanese criteria), as well as the proposed modified criteria. METHODS: The study population included 155 consecutive patients with BD and 170 controls with non-Behçet's rheumatic diseases. Detailed data for all of the subjects were recorded prospectively by the participating physicians on a standard form that listed the clinical features of BD. The sensitivity, specificity, and accuracy of each set of the criteria were measured. RESULTS: Of the three criteria sets employed, the modified criteria were the most accurate, with an accuracy of 96.3%. The ISG criteria often failed to classify the following patients with BD: patients with only oral and genital ulcerations, certain patients with intestinal ulcerations, patients who did not manifest oral ulcerations, and patients with acute disease but fewer than three recurrent oral ulceration relapses in a 1-year period. The Japanese criteria also failed to categorize the following patients with BD: patients with oral and genital ulcerations, and patients with oral ulcerations, skin lesions, and a positive pathergy reaction. In addition, the Japanese criteria misclassified some of the control subjects with non-Behçet's uveitis as having BD. CONCLUSIONS: The results of this study suggest that there are some points that need to be reconsidered in the clinical application of the two pre-existing sets of criteria. Although the modified criteria were the most accurate, further validation studies will be required in other ethnic populations.

A normative study of the Revised Hasegawa Dementia Scale: comparison of demographic influences between the Revised Hasegawa Dementia Scale and the Mini-Mental Status Examination.

BACKGROUND/AIMS: We investigated the demographic influence on the performance of the Revised Hasegawa Dementia Scale (HDS-R) and provided normative data of the HDS-R in the elderly. METHODS: The HDS-R was administered to 803 community-dwelling cognitively normal elderly subjects aged 55 years or over. Cognitive disorders and psychiatric disorders were strictly excluded using the CERAD-K assessment packet and the Mini-International Neuropsychiatric Interview. The demographic influence on the performance of the HDS-R was examined using multiple linear regression analyses, and compared with that on the performance of the Mini-Mental Status Examination (MMSE) using the Chow test and t statistics. Overlapping strata were used in developing age-, education- and gender-specific normative data of the HDS-R. RESULTS: Age, education, and gender influenced significantly the performance of the HDS-R, and explained 22.5% of the total score variance. Older age, lower education, and male gender were associated with lower performance of the HDS-R. However, the demographic influence on the HDS-R was much weaker than that on the MMSE (t = 5.578, d.f. = 800, p < 0.001). The normative data of the HDS-R stratified by age (60-69, 70-79, > or =80), education (0-6, 7-12, > or =13), and gender were presented. CONCLUSIONS: The HDS-R was more robust to demographic influences than the MMSE, and normative data may contribute to improving further its diagnostic accuracy for dementia.

Depression in vascular dementia is quantitatively and qualitatively different from depression in Alzheimer's disease.

BACKGROUND/AIMS: To compare the prevalence and characteristics of depression in vascular dementia (VaD) and Alzheimer's disease (AD) after adjusting for dementia severity and gender. METHODS: One hundred and eight pairs of VaD and AD patients matched for dementia severity and gender were assessed. RESULTS: Major depressive disorder (MDD) was more prevalent in the VaD group than in the AD group (20.4% in VaD, 10.2% in AD, p = 0.04, Cochran-Mantel-Haenszel, CMH, test) regardless of the dementia severity and gender. The odds ratio for developing MDD in the VaD group versus the AD group was estimated to be 2.20 (95% confidence interval = 1.02-4.74). Neurovegetative symptoms such as 'felt tired and weak all the time' (30.6% in VaD, 13.9% in AD, p = 0.003, CMH test) and 'changed weight without trying' (16.7% in VaD, 6.5% in AD, p = 0.02, CMH test) were more prevalent in the VaD group than in the AD group. CONCLUSION: Depression in VaD was quantitatively and qualitatively different from that in AD regardless of the severity of dementia and gender; depression was more prevalent, severer and more retarded and vegetative in VaD than in AD.

Association between the HLA-DRB1 gene and clinical features of systemic sclerosis in Korea.

OBJECTIVE: To determine whether HLA-DR alleles are associated with the development and clinical features of systemic sclerosis (SSc) in Koreans. METHODS: Seventy-nine patients (74 women and five men; 45 diffuse types and 34 limited types; mean age at diagnosis 43.9 years) fulfilling the American College of Rheumatology (ACR) classification criteria for SSc were enrolled. The controls were 144 healthy, disease-free Koreans. HLA-DRB1 genotypes were assessed by the polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. RESULTS: The HLA-DRB1*15 allele was increased in anti-topoisomerase I autoantibody (anti-topo I)-positive SSc patients [p = 0.003, p corrected (p(corr)) = 0.039, odds ratio (OR) = 3.43, 95% confidence interval (CI) 1.45-8.13] compared with controls. The DRB1*11 allele was also observed more frequently in anti-topo I-positive SSc than in controls (13.3% vs. 4.2%) but not statistically significant (p = 0.053, p(corr) = 0.689). In patients with SSc, the DRB1*04 allele was associated with subcutaneous calcinosis (p = 0.048, OR = 4.56, 95% CI 1.07-19.37). Patients with overlap syndrome showed a negative association with the DRB1*04 allele (p = 0.036, OR = 0.26, 95% CI 0.08-0.91). CONCLUSION: The HLA-DRB1*15 allele was associated with the development of anti-topo I-positive SSc in Koreans. In addition, the DRB1*04 allele was associated with certain clinical features in SSc patients.

Potentiation of the toxicity of adriamycin by propranolol.

Both propranolol and adriamycin are biochemically known to inhibit mitochondrial CoQ10-enzymes of myocardial tissue in vitro. Both propranolol and adriamycin are clinically known to cause cardiotoxicity. At two dose levels of propranolol which caused no deaths to mice when administered alone, significant potentiation (p less than 0.01) of the lethality of adriamycin to mice was observed. These data, projected to the clinical situation, seem to contraindicate the administration of the beta-blocker, propranolol, for the hypertension of a cancer patient who is being treated with adriamycin.

Prevention by coenzyme Q10 of the electrocardiographic changes induced by adriamycin in rats.

The administration of adriamycin (ADM) to rats has consistently caused a widening of the QRS complex of the electrocardiogram. When coenzyme Q10 was also administered, beginning two days before ADM, this widening of the QRS complex and the elongation of the Q-T interval were reduced or totally prevented, depending upon conditions. ADM alone or with coenzyme Q10 did not alter the P-R interval. Some control by coenzyme Q10 of the cardiotoxicity of adriamycin in cancer patients is promising.

Transverse grating-assisted narrow-bandwidth acousto-optic tunable filter.

An experimental acousto-optic tunable filter that has a narrow spectral bandwidth (0.2 nm at 1550 nm) and a fast (10-micros) tuning capability with a continuous tuning range of approximately 50 nm is described. The tunable filter consists of an acousto-optic beam deflector with a diffraction grating whose grating vector is transverse to the direction of light propagation.