Gustatory dysfunction in patients with olfactory dysfunction and the associated factors.

BACKGROUND: Little is known about the occurrence of gustatory dysfunction (GD) in relation to different aetiologies of olfactory dysfunction (OD) as assessed by psychophysical chemosensory tests. The aim of this study was to analyse gustatory function in patients with OD and to investigate clinical factors associated with GD. METHODS: A total of 742 individuals who underwent both olfactory and gustatory function tests at a tertiary medical centre from November 2019 to March 2021 were retrospectively enrolled. Olfactory and gustatory function were assessed by the YSK olfactory and gustatory function tests, respectively. Patients with OD were classified into four groups according to the aetiology: sinonasal disease, post-infection OD (PIOD), post-traumatic OD (PTOD), and others. Secondary outcomes included age, sex, smoking history, and alcohol history. RESULTS: Among the 488 patients with OD, 93 (19.1%) showed GD and 395 (80.9%) had normal gustatory function. Only 25 (9.8%) among 254 individuals with normosmia showed GD. Analyses of these frequencies revealed a significant association between OD and GD. In addition, the taste score was significantly lower in patients with OD than individuals with normosmia. The frequency of GD was significantly higher in patients with PTOD (53.6%) than in those with OD of other aetiologies (sinonasal disease, 6.7%; PIOD, 13.0%; others, 24.4%). In the multivariate analysis, age >=5 years and PTOD were associated with a high frequency of GD among patients with OD. CONCLUSIONS: The current study show that GD is significantly associated with OD. In particular, GD is more common in patients with PTOD than in those with OD of other aetiologies.

Safety, tolerability, pharmacodynamics and pharmacokinetics of DWP14012, a novel potassium-competitive acid blocker, in healthy male subjects.

BACKGROUND: A novel potassium-competitive acid blocker, DWP14012, is in clinical development as a potential alternative to proton pump inhibitors for the treatment of acid-related diseases. AIMS: To evaluate the safety, tolerability, pharmacodynamics and pharmacokinetics of DWP14012 in humans. METHODS: A randomised, double-blind, double-dummy, placebo- and active-controlled, single- and multiple-ascending dose (SAD and MAD, respectively) study was conducted in healthy male subjects without Helicobacter pylori infection. Subjects randomly received a single oral dose of 10-320 mg DWP14012, esomeprazole (active comparator) or placebo in the SAD study (n = 72) and once daily doses of 20-160 mg DWP14012, esomeprazole or placebo for 7 days in the MAD study (n = 48; 8:2:2). Tolerability was evaluated using a microRNA-122 assay. Pharmacodynamics were evaluated through 24-hour gastric pH monitoring, and pharmacokinetics were evaluated plasma and urine DWP14012 concentrations. RESULTS: DWP14012 was generally well tolerated. The liver toxicity of DWP14012 was not higher than that of placebo after multiple oral administrations. DWP14012 showed rapid and sustained suppression of gastric acid secretion for 24 hours after dosing. Clear dose-response and exposure-response relationships were observed. Plasma concentrations of DWP14012 increased in a dose-proportional manner in the MAD study, whereas in the SAD study, DWP14012 did not significantly accumulate in the plasma. CONCLUSIONS: DWP14012 was well tolerated, and showed a rapid and long-lasting gastric acid suppression effect in healthy subjects. These results justify further investigation of DWP14012 in patients with acid-related disorders.

Reliability of classification of ring and little finger carpometacarpal joint fracture subluxations: a comparison between two-dimensional computed tomography and three-dimensional computed tomography classifications.

The aims of this study were to develop a classification for ring and little finger carpometacarpal joint fracture subluxations based on three-dimensional computed tomography images and evaluate the inter- and intraobserver reliability of the three-dimensional computed tomography classification. A retrospective review was performed of 30 cases of ring and little finger carpometacarpal joint fracture subluxations from 2005 to 2013. We classified ring and little finger carpometacarpal joint fracture subluxations into three types based on three-dimensional computed tomography images. An orthopaedic surgeon with 2 years of experience, a consultant hand surgeon with 8 years of experience, and a consultant radiologist with 9 years of experience, who were completely blind to the treatment algorithm, evaluated 30 cases twice at a 2-week interval using our new classification based on three-dimensional computed tomography images and the other classification based on two-dimensional computed tomography images. Our three-dimensional computed tomography classification showed almost perfect interobserver and intraobserver reliability and resulted in a better level of agreement than two-dimensional computed tomography classification.

Reliability and validity of lower extremity computed tomography as a screening tool for osteoporosis.

UNLABELLED: We evaluated the correlation between central bone mineral density (BMD) and peripheral bone attenuation using lower extremity computed tomography (CT). A good correlation was found between lower extremity CT and central BMD suggesting that CT is useful for screening osteoporosis, and that peripheral bone attenuation adequately reflects central BMD. INTRODUCTION: This study aimed to evaluate the reliability and validity of CT as a screening tool for osteoporosis and to estimate the correlation between central BMD and peripheral bone attenuation using lower extremity CT. METHODS: In total, 292 patients who underwent a lower extremity, lumbar spine, or abdomen and pelvic CT scan within a 3-month interval of a dual-energy X-ray absorptiometry (DEXA) examination were included. Following reliability testing, bone attenuation of the L1, L2, L3, L4, femoral head, femoral neck, greater trochanter, distal femur, proximal tibia, distal tibia, and talus was measured by placing a circular region of interest on the central part of each bony region on a coronal CT image. Partial correlation was used to assess the correlation between CT and DEXA after adjusting for age and body mass index. RESULTS: In terms of reliability, all bone attenuation measurements, except the femoral neck, showed good to excellent interobserver reliability (intraclass correlation coefficients, 0.691-0.941). In terms of validity, bone attenuation of the L1 to L4, femoral neck, and greater trochanter on CT showed significant correlations with BMD of each area on DEXA (correlation coefficients, 0.399-0.613). Bone attenuation of the distal tibia and talus on CT showed significant correlations with BMD of all parts on DEXA (correlation coefficients, 0.493-0.581 for distal tibia, 0.396-0.579 for talus). CONCLUSION: Lower extremity CT is a useful screening tool for osteoporosis, and peripheral bone attenuation on lower extremity CT adequately reflects central BMD on DEXA.

Predictors of renal relapse in Korean patients with lupus nephritis who achieved remission six months following induction therapy.

Renal relapse in patients with lupus nephritis (LN) is a risk factor for poor renal function. Therefore, there is a need to identify clinical and serological risk factors for renal relapse. A total of 108 patients with LN were enrolled in this study. All the subjects had achieved complete remission or partial remission following six months of induction therapy. We retrospectively analyzed their clinical and laboratory indices, final renal function, and kidney biopsy findings. The median follow-up period after LN diagnosis was 81 months. Renal relapse had occurred in 36 patients; it occurred in 38% and 46% of patients within five and 10 years after achievement of renal remission, respectively. There was no difference between the relapsed rate in patients with complete remission and that in those with partial remission. Clinical variables at LN onset and renal biopsy findings in the patients with sustained remission and relapsed patients were also not different. The probability of renal relapse was significantly higher in patients with an earlier age of onset of systemic lupus erythematosus (SLE) (≤ 28 years versus >28 years; HR 7.308, P=0.001), seronegativity for anti-Ro antibody (seronegativity versus seropositivity; HR 3.514, P=0.007), and seropositivity for anti-dsDNA antibody at six months after initiation of induction therapy (HR 8.269, P=0.001). Our study demonstrated that early onset of SLE, seronegativity for anti-Ro antibody and increased anti-dsDNA antibody following six months of induction therapy independently predict renal relapse among the LN patients.

Incoherent c-axis interplane response of the iron chalcogenide FeTe(0.55)Se(0.45) superconductor from infrared spectroscopy.

We report on the interplane c-axis electronic response of FeTe(0.55)Se(0.45) investigated by infrared spectroscopy. We find that the normal-state c-axis electronic response of FeTe(0.55)Se(0.45) is incoherent and bears significant similarities to those of mildly underdoped cuprates. The c-axis optical conductivity σ(c)(ω) of FeTe(0.55)Se(0.45) does not display well-defined Drude response at all temperatures. As temperature decreases, σ(c)(ω) is continuously suppressed. The incoherent c-axis response is found to be related to the strong dissipation in the ab-plane transport: a pattern that holds true for various correlated materials as well as FeTe(0.55)Se(0.45).

Diffuse alveolar hemorrhage in systemic lupus erythematosus: risk factors and clinical outcome: results from affiliated hospitals of Catholic University of Korea.

This study was undertaken to investigate clinical characteristics of diffuse alveolar hemorrhage (DAH) in patients with systemic lupus erythematosus (SLE) and to determine risk factors and clinical outcomes of DAH in SLE patients. Among the 1521 patients with SLE admitted between January 1993 and June 2009 to affiliated hospitals of Catholic University of Korea, 21 SLE were admitted for DAH. The inclusion criteria for DAH was defined as new infiltrates on chest radiographs, an acute hemoglobin drop of at least 1.5 g/dl in the absence of an obvious source of bleeding, and one or more of the following signs: hemoptysis, hypoxemia, bronchoscopic or biopsy evidence of DAH. Included as disease controls were 83 SLE patients, matched for age and sex, who were admitted for other manifestations. Data based on medical records were analyzed retrospectively. There were no significantly differing demographic characteristics between SLE patients with DAH and those with other manifestations. Multivariate analysis demonstrated coexisting neuropsychiatric lupus (p = 0.002) and high SLE disease activity index scores (SLEDAI > 10) as independent risk factors in the development of DAH (p = 0.029). Among the 21 SLE patients with DAH, 13 died during the admission period (in-hospital mortality rate: 61.9%). Mortality was associated with infection and requirements of mechanical ventilation. Collectively, SLE patients who have neuropsychiatric manifestations or are in the active stage of the disease have an increased risk for developing DAH. Due to the high mortality of SLE patients with DAH, early recognition of risk factors and appropriate intervention is essential.

Idiopathic transverse myelitis presenting as the Brown-Sequard syndrome.

STUDY DESIGN: Case report. OBJECTIVES: To report an unusual case of Brown-Sequard syndrome (BSS) associated with idiopathic transverse myelitis (TM). SETTING: Department of Neurosurgery, Chonnam National University Hospital, Gwangju, South Korea. METHODS: A 38-year-old man presented with left leg weakness and right-sided decrease in sensation at the T11 level below. Magnetic resonance images (MRI) of the thoracic spine showed diffuse swelling of the spinal cord spanning the fifth to the eighth thoracic vertebra. The lesion had high signal intensity on T2-weighted images. Eccentric nodular enhancement within the left anterolateral aspect of the spinal cord was appreciated with gadolinium administration. RESULTS: The patient was treated with pulsed methylprednisone and showed marked improvement in neurological function within 3 days. An MRI at 5-month follow-up demonstrated complete resolution of the abnormalities. CONCLUSION: This case illustrates a rare case of BSS caused by idiopathic TM of the thoracic spinal cord. TM should be considered in the differential diagnosis of BSS.

Ceramide inhibits cell proliferation through Akt/PKB inactivation and decreases melanin synthesis in Mel-Ab cells.

Ceramide is a bioactive sphingolipid that mediates a variety of cell functions. However, the effects of ceramide on cell growth and the melanogenesis of melanocytes are not known. In the present study, we investigated the actions of cell-permeable ceramide and its possible role in the signaling pathway of a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Our results show that C2-ceramide inhibits DNA synthesis in Mel-Ab cells and G361 human melanoma cells in a dose-dependent manner. Cell cycle analysis confirmed the inhibition of DNA synthesis by a reduction in the S phase. To investigate the ceramide signaling pathway, we studied whether C2-ceramide is able to influence extracellular signal-regulated kinase (ERK) and/or Akt/protein kinase B (PKB) activation. We demonstrated that phosphorylated Akt/PKB is decreased by C2-ceramide, whereas phosphorylated ERK was only slightly affected. Therefore, the C2-ceramide-induced inactivation of Akt/PKB may be closely related to the reduced cell proliferation of Mel-Ab cells. Furthermore, we assessed the effects of C2-ceramide on the pigmentation of Mel-Ab cells. The results obtained showed that the melanin content of cells was significantly reduced by C2-ceramide at concentrations in the range of 1-10 microM, and that the pigmentation-inhibiting effect of C2-ceramide is much greater than that of kojic acid at 1-100 microM. In addition, we found that the activity of tyrosinase is reduced by C2-ceramide treatment. Our results demonstrate that C2-ceramide reduces the pigmentation of Mel-Ab cells by inhibiting tyrosinase activity.

Inhibitory effect of mast cell-mediated immediate-type allergic reactions by sulfapyridine.

We examined the effect of sulfapyridine on mast cell-mediated immediate-type allergic reactions. Sulfapyridine (1 and 10 microg/kg) significantly inhibited systemic allergic reaction induced by compound 48/80 in rats. Sulfapyridine (1 and 10 microg/kg) also inhibited significantly local mast cell-mediated immediate-type allergic reactions activated by anti-dinitrophenyl (DNP) IgE. Moreover, sulfapyridine inhibited histamine release dose-dependently in the rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. When sulfapyridine was added, the level of cAMP in RPMC, transiently and significantly increased about 4-fold compared with that of basal cells. These results indicate that sulfapyridine inhibits mast cell-mediated immediate-type allergic reactions in vivo and in vitro.

Pyrithione, a zinc ionophore, inhibits NF-kappaB activation.

Pyrrolidine dithiocarbamate (PDTC) suppresses NF-kappaB activity and exhibits cytotoxic effects in bovine cerebral endothelial cells (BCECs), and we have previously reported that these PDTC effects were accompanied by an increase in intracellular zinc levels. To further explore the role of zinc in the modulation of NF-kappaB activation, we studied the effect of pyrithione, a zinc ionophore, on NF-kappaB activation in BCECs. Pyrithione inhibited NF-kappaB activity in a time- and dose-dependent manner. Ca-EDTA, but not Zn-EDTA, prevented pyrithione inhibition of NF-kappaB activity. Pyrithione increased the intracellular zinc level within 15 min. This effect was also abolished by Ca-EDTA, but not by Zn-EDTA. The potency of pyrithione on NF-kappaB inhibition and zinc influx was approximately one order of magnitude more potent than PDTC. These findings establish the regulatory role of intracellular zinc levels on NF-kappaB activity in BCECs.

Analysis of induced sputum to examine the effects of inhaled corticosteroid on airway inflammation in children with asthma.

BACKGROUND: Analysis of induced sputum can be performed safely in children with asthma and is useful for both cellular and biochemical markers of inflammation. Glucocorticosteroid inhalation has become the first line therapy for chronic asthma by suppressing airway inflammation, which produces the decrease of bronchial hyperreactivity and reduces the number of eosinophil in bronchial submucosa. OBJECTIVE: To determine the characteristics of the inflammatory cells and their markers in sputum and to examine the pharmacokinetic effects of glucocorticoid within 3 hours after inhalation therapy on FEV1 and sputum inflammatory indices in children with clinically defined chronic asthma. METHODS: Thirty subjects with asthma included 14 current symptomatic asthmatics and 14 normal controls inhaled 4.5% hypertonic saline for 10 minutes by nebulizer. The expectorated sputum were collected from all asthmatics before and 3 hours after corticosteroid inhalation for children with asthma and were reduced by dithiotreitol. Total cell counts and differentials were determined. ECP was measured by CAP system. Interleukin-5, GM-CSF and albumin were measured by double sandwich ELISA. RESULTS: The mean eosinophil percentage and ECP in induced sputum of asthmatics were significantly higher than that of controls. The induced sputum samples obtained after glucocorticoid inhalation showed a significant reduction in mean eosinophil percentage, but FEV1, IL-5, GM-CSF, albumin, and ECP values were not significantly decreased. CONCLUSION: The present results in induced sputum may be interpreted to reflect direct steroid action on airways and lack of effect on bone marrow effectors at 3 hours after glucocorticoid inhalation.