Fesoterodine, an antimuscarinic drug, is widely used to treat overactive bladder syndrome. However, there is little information about its effects on vascular K+ channels. In this study, voltage-dependent K+ (Kv) channel inhibition by fesoterodine was investigated using the patch-clamp technique in rabbit coronary artery. In whole-cell patches, the addition of fesoterodine to the bath inhibited the Kv currents in a concentration-dependent manner, with an IC50 value of 3.19 ± 0.91 μM and a Hill coefficient of 0.56 ± 0.03. Although the drug did not alter the voltage-dependence of steady-state activation, it shifted the steady-state inactivation curve to a more negative potential, suggesting that fesoterodine affects the voltage-sensor of the Kv channel. Inhibition by fesoterodine was significantly enhanced by repetitive train pulses (1 or 2 Hz). Furthermore, it significantly increased the recovery time constant from inactivation, suggesting that the Kv channel inhibition by fesoterodine is use (state)-dependent. Its inhibitory effect disappeared by pretreatment with a Kv 1.5 inhibitor. However, pretreatment with Kv2.1 or Kv7 inhibitors did not affect the inhibitory effects on Kv channels. Based on these results, we conclude that fesoterodine inhibits vascular Kv channels (mainly the Kv1.5 subtype) in a concentration- and use (state)-dependent manner, independent of muscarinic receptor antagonism.

Background: Lichenoid drug eruption (LDE) is a relatively rare form of cutaneous drug eruption and that resembles lichen planus on a clinical and histological basis. Although there are some studies on histopathological findings of LDE, studies on clinical findings of LDE are limited. Objective: To investigate the clinical and histopathologic findings and prognosis of LDE. Methods: We retrospectively investigated the clinicopathologic findings of LDE patients who visited Kosin University Gospel Hospital between 1990 and 2020. Results: This study included 44 LDE patients (male:female=1.4:1). The most common causative drug was anti-tuberculous drugs (52.3%), followed by 5-fluorouracil (11.4%), and captopril (9.1%). There were pruritic erythematous scaly or lichenoid patches and plaques in all cases. The most frequently involved sites were trunk and extremities. Notably, 15 cases (34.1%) involving the scalp and 3 cases (6.8%) involving the oral mucosa. Treatment modalities included oral, topical corticosteroid, and oral antihistamines. Among 44 cases, 28 patients discontinued the causative agent, and 16 patients continued to use it after diagnosis of LDE. The mean duration of treatment for patients who discontinued or did not discontinue the causative drugs was 4, 10 weeks, respectively. The most commonly observed histopathologic findings were superficial and deep perivascular infiltration of inflammatory cells (100.0%) and eosinophil infiltration (93.2%). Conclusion LDE can be differentiated from idiopathic lichen planus by clinicopathologic findings. LDE appears to be a mild form of drug eruption in which symptoms can be controlled with conservative treatment, even without the cessation of causative drugs for the treatment of the underlying disease.

To investigate the adverse effects of clozapine on cardiovascular ion channels, we examined the inhibitory effect of clozapine on voltage-dependent K+(Kv) channels in rabbit coronary arterial smooth muscle cells. Clozapine-induced inhibition of Kv channels occurred in a concentration-dependent manner with an halfinhibitory concentration value of 7.84 ± 4.86 µM and a Hill coefficient of 0.47 ± 0.06.Clozapine did not shift the steady-state activation or inactivation curves, suggesting that it inhibited Kv channels regardless of gating properties. Application of train pulses (1 and 2 Hz) progressively augmented the clozapine-induced inhibition of Kv channels in the presence of the drug. Furthermore, the recovery time constant from inactivation was increased in the presence of clozapine, suggesting that clozapineinduced inhibition of Kv channels is use (state)-dependent. Pretreatment of a Kv1.5 subtype inhibitor decreased the Kv current amplitudes, but additional application of clozapine did not further inhibit the Kv current. Pretreatment with Kv2.1 or Kv7 subtype inhibitors partially blocked the inhibitory effect of clozapine. Based on these results, we conclude that clozapine inhibits arterial Kv channels in a concentrationand use (state)-dependent manner. Kv1.5 is the major subtype involved in clozapineinduced inhibition of Kv channels, and Kv2.1 and Kv7 subtypes are partially involved.

Background: Infections caused by multidrug-resistant Pseudomonas aeruginosa (MDRPA) have been on the rise worldwide, and delayed active antimicrobial therapy is associated with high mortality. However, few studies have evaluated increases in P. aeruginosa infections with antimicrobial resistance and risk factors for such antimicrobial resistance in Korea. Here, we analyzed changes in antimicrobial susceptibility associated with P. aeruginosa bacteremia and identified risk factors of antimicrobial resistance. Methods: The medical records of patients with P. aeruginosa bacteremia who were admitted to a tertiary hospital between January 2009 and October 2020 were retrospectively reviewed. Antibiotic resistance rates were compared among the time periods of 2009–2012, 2013–2016, and 2017–2020 and between the intensive care unit (ICU) and non-ICU setting. Empirical antimicrobial therapy was considered concordant, if the organism was susceptible to antibiotics in vitro, and discordant, if resistant. Results: During the study period, 295 patients with P. aeruginosa bacteremia were identified. The hepatobiliary tract (26.8%) was the most common primary site of infection. The rates of carbapenem-resistant P. aeruginosa (CRPA), MDRPA, and extensively drug-resistant P. aeruginosa (XDRPA) were 24.7%, 35.9%, and 15.9%, respectively. XDRPA showed an increasing trend, and CRPA, MDRPA, and XDRPA were also gradually increasing in non-ICU setting. Previous exposure to fluoroquinolones and glycopeptides and urinary tract infection were independent risk factors associated with CRPA, MDRPA, and XDRPA. Previous exposure to carbapenems was an independent risk factor of CRPA. CRPA, MDRPA, and XDRPA were associated with discordant empirical antimicrobial therapy. Conclusion The identification of risk factors for antimicrobial resistance and analysis of antimicrobial susceptibility might be important for concordant empirical antimicrobial therapy in patients with P. aeruginosa bacteremia.

BACKGROUND: Acute ischemic stroke patients with malignant infarct cores were primarily treated with neurocritical care based on reperfusion and hypothermia. We evaluated the predictors for malignant progression and functional outcomes. METHODS: From January 2010 to March 2015 ischemic stroke patients with large vessel occlusion of the anterior circulation with infarct volume >82 mL on baseline diffusion weighted image (DWI) within 6 hours from onset, with National Institutes of Health Stroke Scale ≥15 were included. All patients were managed with intent for reperfusion and neurocritical care. Malignant progression was defined as clinical signs of progressive herniation. Predictive factors for malignant progression and outcomes of decompressive hemicraniectomy (DHC) were evaluated. RESULTS: In total, 49 patients were included in the study. Among them, 33 (67.3%) could be managed with neurocritical care and malignant progression was observed in the remainder. Decompressive surgery was performed in nine patients (18.4%). Factors predictive of malignant progression were initial DWI volumes (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00 to 1.02; P=0.046) and parenchymal hematoma (OR, 6.77; 95% CI, 1.50 to 30.53; P=0.013) on computed tomography taken at Day 1. Infarct volume of >210 mL predicted malignant progression with 56.3% sensitivity and 90.9% specificity. Among the malignant progressors, 77.7% resulted in grave outcomes even with DHC, while all patients who declined surgery died. CONCLUSION: Acute ischemic stroke patients with malignant cores between 82 to 209 mL can be primarily treated with neurocritical care based on reperfusion and hypothermia with feasible results. In patients undergoing surgical decompression due to malignant progression, the functional outcomes were not satisfactory.
Brain Edema ; Critical Care ; Decompression, Surgical ; Decompressive Craniectomy ; Diffusion ; Hematoma ; Humans ; Hypothermia ; Hypothermia, Induced ; Infarction, Middle Cerebral Artery ; National Institutes of Health (U.S.) ; Reperfusion ; Sensitivity and Specificity ; Stroke ; Thrombectomy

BACKGROUND: This study aimed to determine GATA1 expression levels to better characterize subgroups in BCR/ABL1-negative myeloproliferative neoplasms (MPNs). METHODS: This study enrolled 49 patients diagnosed as having BCR/ABL1-negative MPN on the basis of the 2016 World Health Organization classification : nine polycythemia vera (PV), 17 essential thrombocythemia (ET), 12 prefibrotic primary myelofibrosis (prePMF), and 11 overt primary myelofibrosis (PMF). Relevant clinical and laboratory data were retrieved from the medical records. The molecular analysis of CALR and MPL mutations and quantification of JAK2 V617F allele burden were performed. GATA1 expression was assessed by an immunohistochemical assay on bone marrow biopsy. GATA1 expression was analyzed serially in 18 patients. RESULTS: GATA1 expression decreased significantly in PMF compared with that in other subtypes, while no statistical difference was identified between ET and prePMF. GATA1 expression did not differ according to the mutation profiles or the allele burden of JAK2 V617F, but it decreased significantly in patients with overt fibrosis or leukemic transformation. CONCLUSIONS: Our results suggest that GATA1 expression is significantly low in PMF and decreases with progressive fibrosis and possibly with leukemic transformation, although our attempt to accurately distinguish between subgroups using GATA1 immunohistochemical approach did not achieve statistical significance. A large patient cohort with long term follow-up is required to evaluate the prognostic value of GATA1 expression.
Alleles ; Biopsy ; Bone Marrow ; Classification ; Cohort Studies ; Fibrosis ; Follow-Up Studies ; Humans ; Medical Records ; Polycythemia Vera ; Primary Myelofibrosis ; Thrombocythemia, Essential ; World Health Organization

The general concept and initial approach to syncope patients has been mentioned in the general sections. This special sections have been described the characteristics, diagnosis, and treatment with patient education for the each syncope. It has been described in order of reflex syncope, orthostatic hypotension, postural orthostatic tachycardia syndrome (POTS), cardiac syncope, and unexplained syncope. Several clinical issues will have been dealt with in special issues. Neurological assessment is added when the patients were diagnosed with psychogenic pseudosyncope (PPS). Although many childhood syncope caused by reflex syncope, they are also presented as syncope caused by arrhythmic events in patients with congenital heart disease. In the elderly patients, syncope is because of not only a single cause of syncope but a combination of various conditions. In case of a syncope patient visiting the emergency department, a standardized systematic approach will be required to determine whether hospitalize the patient according to the risk of recurrence and the needs for the syncope management unit. We also mention recommendations on the limits of driving, exercising and social life style that are relevant to syncope in all patients. In this guideline, we reviewed the Korean published literatures and European/American guidelines on syncope. We, writing and publishing committee for evaluation and management guidelines of syncope in the Korean Society for Holter and Noninvasive Electrocardiography (KSHNE) under the Korean Heart Rhythm Society (KHRS) are very pleased to be able to publish this guideline. We also hope this guideline will be a good support to manage the syncope patients and a useful trigger for further research in Korea.
Aged ; Diagnosis ; Electrocardiography ; Emergency Service, Hospital ; Heart ; Heart Defects, Congenital ; Hope ; Humans ; Hypotension, Orthostatic ; Korea ; Life Style ; Patient Education as Topic ; Postural Orthostatic Tachycardia Syndrome ; Recurrence ; Reflex ; Syncope ; Writing

Syncope is a very common symptom that occurs in all age groups, especially in adolescents and elderly people. The cause of syncope is very diverse, and patients with syncope visit various medical departments such as general medicine, cardiology, neurology, and emergency medicine. If we do not perform appropriate diagnostic tests based on detailed history of syncope, we may have some difficulty to identify the cause of syncope. Failure to identify the cause of syncope can lead to physical trauma due to recurrence of syncope or may increase the risk of cardiovascular events in the future. However, there is no Korean guidelines for the diagnosis and treatment of syncope yet. Considering these circumstances in Korea, we prepared writing and publishing committee for evaluation and management guidelines of syncope in the Korean Society for Holter and Noninvasive Electrocardiology (KSHNE) under the Korean Heart Rhythm Society (KHRS). In this guideline, we reviewed the Korean published literatures and European / American guidelines on syncope.
Adolescent ; Aged ; Cardiology ; Diagnosis ; Diagnostic Tests, Routine ; Emergency Medicine ; Heart ; Humans ; Korea ; Neurology ; Recurrence ; Syncope ; Writing

BACKGROUND/OBJECTIVES: Although Korean fermented foods contain large amounts of salt, which is known to exacerbate health problems, these foods still have beneficial effects such as anti-hypertension, anti-cancer, and anti-colitis properties. We hypothesized that ganjang may have different effects on blood pressure compared to same concentrations of salt. MATERIALS/METHODS: Sprague-Dawley rats were divided into control (CT), NaCl (NC), and ganjang (GJ) groups and orally administered with 8% NaCl concentration for 9 weeks. The systolic blood pressure (SBP), serum chemistry, Na⁺ and K⁺ concentrations and renal gene expressions were measured. RESULTS: The SBP was significantly increased in the NC group compared to the GJ and CT groups. In addition, the Na+ concentration in urine was higher in the GJ and NC groups than the CT group, but the urine volume was increased in the GJ group compared to the other groups. The serum renin levels were decreased in the GJ group compared to the CT group, while the serum aldosterone level was decreased in the GJ group relative to the NC group. The mRNA expression of the renin, angiotensin II type I receptor, and mineralocorticoid receptor were significantly lower in the GJ group compared to other groups. Furthermore, GJ group showed the lowest levels of genes for Na⁺ transporter in kidney cortex such as Na⁺/K⁺ ATPaseα1 (NKAα1), Na⁺/H⁺ exchanger 3 (NHE3), Na⁺/HCO₃⁻ co-exchanger (NBC), and carbonic anhydrases II (CAII). CONCLUSIONS: The decreased SBP in the GJ could be due to decreased renin and aldosterone levels in serum and increased urinary volume and excretion of Na⁺ with its transporter gene alteration. Therefore, ganjang may have antihypertensive effect despite its high contents of salt.
Aldosterone ; Angiotensin II ; Blood Pressure ; Carbonic Anhydrases ; Chemistry ; Gene Expression ; Hypertension ; Kidney Cortex ; Rats, Sprague-Dawley* ; Receptors, Mineralocorticoid ; Renin ; Renin-Angiotensin System ; RNA, Messenger