OBJECTIVE: Tyrosine kinase inhibitors may be useful in the management of cerebral vasospasm. It has not yet reported whether potassium channel plays a role in tyrosine kinase inhibitors-induced vascular relaxation of cerebral artery. This study is undertaken to clarify the role of potassium channel in tyrosine kinase inhibitors-induced vascular relaxation, and to investigate the effect of tyrosine kinase inhibitors on outward potassium currents in freshly isolated smooth muscle cells from rat basilar artery. METHODS: The isolation of rat basilar smooth muscle cells was performed by special techniques. The whole cell currents were recoreded by whole cell patch clamp technique in freshly isolated smooth muscle cells from rat basilar artery. RESULTS: In present study, genistein(n=10), tyrphostin A-23(n=10), A-25(n=10) 30microM into bath solution increased the amplitude of the outward K+ current which was completely blocked by large conductance calcium-activated potassium channel(BK(Ca)) blocker, iberiotoxin(0.1microM), and calcium chelator, BAPTA, in whole cell mode. In contrast, diadzein 30microM(n=10), inactive analogue of genistein, did not increase the amplitude of the outward K+ current. CONCLUSION: Our results suggest tyrosine kinase inhibitors such as genistein, tyrphostin A-23 and A-25 increase the BK(Ca) channel activity in cerebral basilar smooth muscle cells, thereby contributing to the relaxation of cerebral artery.
Animals ; Basilar Artery ; Baths ; Calcium ; Cerebral Arteries ; Genistein ; Muscle, Smooth* ; Myocytes, Smooth Muscle* ; Potassium ; Potassium Channels ; Protein-Tyrosine Kinases* ; Rats* ; Relaxation ; Tyrosine* ; Vasospasm, Intracranial

OBJECTIVE: Tyrosine kinase inhibitors may be useful in the management of cerebral vasospasm. It has not yet been reported whether L-type Ca2+ channels play a role in tyrosine kinase inhibitors-induced vascular relaxation of cerebral artery. This study was undertaken to clarify the role of L-type Ca2+ channels in tyrosine kinase inhibitors-induced vascular relaxation, and to investigate the effect of tyrosine kinase inhibitors on L-type Ca2+ channels currents in freshly isolated smooth muscle cells from rat basilar artery. METHODS: The isolation of rat basilar smooth muscle cells was performed by special techniques. The whole cell currents were recorded by whole cell patch clamp technique in freshly isolated smooth muscle cells from rat basilar artery. RESULTS: Patch clamp studies revealed a whole-cell current which resembles the L-type Ca2+ current reported by others. The amplitude of this current was decreased by nimodipine and increased by Bay K 8644. Genistein(n=5), tyrphostin A-23(n=3), A-25(n=6) 30micrometer reduced the amplitude of the L-type Ca2+ channel current in whole cell mode. In contrast, diadzein 30 micrometer (n=3), inactive analogue of genistein, did not decrease the amplitude of the L-type Ca2+ channels current. CONCLUSION: These results suggest that tyrosine kinase inhibitors such as genistein, tyrphostin A-23, A-25 may relax cerebral vessel through decreasing level of intracellular calcium, [Ca2+]i, by inhibition of L-type Ca2+ channel.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; Animals ; Basilar Artery ; Calcium* ; Cerebral Arteries ; Genistein ; Muscle, Smooth* ; Myocytes, Smooth Muscle* ; Nimodipine ; Patch-Clamp Techniques ; Protein-Tyrosine Kinases* ; Rats* ; Relaxation ; Tyrosine* ; Vasospasm, Intracranial

PURPOSE: Soft tissue sarcomas have a wide variety of manifestation and its course is still unpredictable in many cases. This study altlempts to analyze the meaningful prognostic factors and to find optimal treatment strategies for each clinical stage. MATERIALS AND METHODS: From May 1985 to Mar. 1997, 432 soft tissue sarcomas were enlisted and 319 cases were eligible for this retrospective study. Staging followed AJCC classification and there were 34 stage I, 69 stage II, 151 stage III and 64 cases of stage IV. For stage I and II, operation was a major tool. Radiotherapy and chemotherapy were added for each situation. Intensive chemotherapy and surgery were done for stage III and IV. Metastasectomy was added in feasible cases. RESULTS: Actual survival rate for the 319 cases was 50% at 152 months. Disease free survival for stage I, II, III was 84%, 41%, and 38%, respectively. The stage itself had a statistical significance (P<0.00001). In univariate analysis, surgical margin in stage II and local recurrence in stage III had statistical significance. Multivariate study revealed the local recurrence as the only meaningful factor in stage I, II, III. An aggressive treatment for stage IV and I, II, III with late metastasis group had significant gain on survival. CONCLUSIONS: The stage itself predicts the course of soft tissue sarcomas. Evaluation of sound surgical margin to prevent the local recurrence is necessary.
Classification ; Disease-Free Survival ; Drug Therapy ; Metastasectomy ; Neoplasm Metastasis ; Radiotherapy ; Recurrence ; Retrospective Studies ; Sarcoma* ; Survival Rate

PURPOSE: Although survival of osteosarcoma patient has markedly improved, cases of non-responders to chemotherapy and late-relapsers are still perplexing. Our strategy was to analyze the impact of chemotherapy and surgery on the survival for each stage, and to evaluate long-term survival and find prognostic factors within the same stage. MATERIALS AND METHODS: From May 1985 to Feb. 1999, 461 osteosarcomas were enlisted at our department and among them 348 cases were evaluable. There were 1 IB, 4 IIA, 302 IIB, and 41 IIIB. Two hundred and fifty-five (IIA/IIB:4/251) out of 348 cases followed our protocol of chemotherapy and surgery. Two hundred and ten cases had neoadjuvant chemotherapy and 45 had adjuvant only. RESULTS: Eleven year event free survival of the neoadjuvant group was 56.7%. On univariate analysis for 210 neoadjuvant cases, age (<13yrs), type of surgery (amputation), type of chemotherapy (methotrexate, adriamycin, cisplatin), pathologic response (>90%), local recurrence, pathologic fracture, location and size were statistically significant. But multivariate one revealed age, type of surgery, local recurrence and pathologic response as useful factors. There were 12 local recurrences (5.7%) and 100 metastasis among 255 stage II and their average onset from treatment was 17.8 month. Survival after metastasis was 5.6% at 55 months and the aggressively treated group made gains in survival (P<0.0001). Survival of 41 stage III was 0% at 64 months and this group also had an advantage in survival through intensive chemotherapy and surgery for primary and metastatic lesions (p=0.04). CONCLUSION: Long-term survival of the treated 255 stage II group was 55% at 14 years. For stage II: age, local recurrence and pathologic response were meaningful prognostic factors. Aggressive surgery and chemotherapy were necessary to improve the survival of stage III and stage II with late metastasis group.
Disease-Free Survival ; Doxorubicin ; Drug Therapy ; Fractures, Spontaneous ; Humans ; Korea* ; Neoplasm Metastasis ; Osteosarcoma* ; Recurrence ; Survival Rate*

Tracheobronchopathia osteochondroplastica is a rarely reported disease, and the clinical course is usually benign. But it may cause significant tracheal stenosis. Although it is usually found by autopsy, with the development of bronchoscopic examination and computed tomography, antemortem diagnosis is increasing. We experienced a case of tracheobronchopathia osteochondroplastica which caused severe dyspnea, we did laryngoscopic examination, biosy and treated with tracheostomy.
Airway Obstruction* ; Autopsy ; Diagnosis ; Dyspnea ; Tracheal Stenosis ; Tracheostomy

OBJECTIVE: Papaverine has been used in treating vasospasm following subarachnoid hemorrhage(SAH). However, its action mechanism for cerebral vascular relaxation is not clear. Potassium channels are closely related to the contraction and relaxation of cerebral smooth muscle. Therefore, to identify the role of potassium and calcium channels in papaverine-induced vascular relaxation, we examine the effect of papaverine on potassium channels in freshly isolated smooth muscle cells from rat basilar artery. METHODS: The isolation of rat basilar smooth muscle cells was performed by special techniques. The whole cell currents were recorded by whole cell patch clamp technique in freshly isolated smooth muscle cells from rat basilar artery. Papaverine was added to the bath solution. RESULTS: Papaverine of 100 microM into bath solution increased the amplitude of the outward K+ current which was completely blocked by BKCa(large conductance calcium dependent potassium channels)blocker, IBX(iberiotoxin), and calcium chealator, BAPTA(1, 2-bis(o-aminophenoxy)ethane-N, N, N', N'-tetraacetic acid), in whole cell mode. CONCLUSION: These results strongly suggest that potassium channels may play roles in papaverine-induced vascular relaxation in rat basilar artery.
Animals ; Basilar Artery ; Baths ; Calcium ; Calcium Channels ; Muscle, Smooth* ; Myocytes, Smooth Muscle* ; Papaverine* ; Patch-Clamp Techniques ; Potassium ; Potassium Channels ; Rats* ; Relaxation

Changes in the prevalence of disease over time provide valuable information from a public health perspective. We used data from Korea Military Manpower Administration medical examinations for conscription between 2003 and 2019 (n = 5,355,941), which involved young men aged 19 years, to observe changes in liver disease over time at a population level. Trends in the prevalence of hepatitis B surface antigen (HBsAg), elevated alanine aminotransferase (ALT) levels, the fibrosis-4 (FIB-4) index, obesity, and hypertension were assessed. The prevalence of HBsAg steadily decreased from 3.19% for men born in 1984 to 0.18% for men born in 2000. Among HBsAg-negative subjects, the prevalence of elevated ALT levels increased from 13.15% for men born in 1986 to 16.48% for men born in 2000. The prevalence of obesity, hypertension and the proportion with high FIB-4 scores (≥ 1.45) also increased. This population-based nationwide analysis showed a decreasing trend of HBsAg and increasing trends of possible non-alcoholic fatty liver disease.

Background: s/Aims: Systemic therapy is the current standard treatment for hepatocellular carcinoma (HCC) with extrahepatic metastasis (EHM). However, some patients with HCC and EHM undergo transarterial chemoembolization (TACE) to manage intrahepatic tumors. Herein, we aimed to explore the appropriateness of TACE in patients with HCC and EHM in an era of advanced systemic therapy. Methods: This study analyzed 248 consecutive patients with HCC and EHM (median age, 58.5 years; male, 83.5%; Child-Pugh A, 88.7%) who received TACE or systemic therapy (83 sorafenib, 49 lenvatinib, 28 immunotherapy-based) between January 2018 and January 2021. Results: Among the patients, 196 deaths were recorded during a median follow-up of 8.9 months. Patients who received systemic therapy had a higher albumin-bilirubin grade, elevated tumor markers, an increased number of intrahepatic tumors, larger-sized tumors, and more frequent portal vein invasion than those who underwent TACE. TACE was associated with longer median overall survival (OS) than sorafenib (15.1 vs. 4.7 months; 95% confidence interval [CI], 11.1-22.2 vs. 3.7-7.3; hazard ratio [HR], 1.97; P<0.001). After adjustment for potential confounders, TACE was associated with statistically similar survival outcomes to those of lenvatinib (median OS, 8.0 months; 95% CI, 6.5-11.0; HR, 1.21; P=0.411) and immunotherapies (median OS, 14.3 months; 95% CI, 9.5-27.0; HR, 1.01; P=0.973), demonstrating survival benefits equivalent to these treatments. Conclusions In patients with HCC and EHM, TACE can provide a survival benefit comparable to that of newer systemic therapies. Accordingly, TACE remains a valuable option in this era of new systemic therapies.

Background/Aims: Improved knowledge of local epidemiology and predicting risk factors of multidrug-resistant (MDR) bacteria are required to optimize the management of infections. This study examined local epidemiology and antibiotic resistance patterns of liver cirrhosis (LC) patients and evaluated the predictors of MDR bacteremia in Korea. Methods: This was a retrospective study including 140 LC patients diagnosed with bacteremia between January 2017 and December 2022. Local epidemiology and antibiotic resistance patterns and the determinants of MDR bacteremia were analyzed using logistic regression analysis. Results: The most frequently isolated bacteria, from the bloodstream, were Escherichia coli (n = 45, 31.7%) and Klebsiella spp. (n = 35, 24.6%). Thirty-four isolates (23.9%) were MDR, and extended-spectrum beta-lactamase E. coli (52.9%) and methicillin-resistant Staphylococcus aureus (17.6%) were the most commonly isolated MDR bacteria. When Enterococcus spp. were cultured, the majority were MDR (MDR 83.3% vs. 16.7%, p = 0.003), particularly vancomycin-susceptible Enterococcus faecium. Antibiotics administration within 30 days and/or nosocomial infection was a significant predictor of MDR bacteremia (OR: 3.40, 95% CI: 1.24–9.27, p = 0.02). MDR bacteremia was not predicted by sepsis predictors, such as positive systemic inflammatory response syndrome (SIRS) or quick Sequential Organ Failure Assessment (qSOFA). Conclusions More than 70% of strains that can be treated with a third-generation cephalosporin have been cultured. In cirrhotic patients, antibiotic administration within 30 days and/or nosocomial infection are predictors of MDR bacteremia; therefore, empirical administration of broad-spectrum antibiotics should be considered when these risk factors are present.

Background: s/Aims: Systemic therapy is the current standard treatment for hepatocellular carcinoma (HCC) with extrahepatic metastasis (EHM). However, some patients with HCC and EHM undergo transarterial chemoembolization (TACE) to manage intrahepatic tumors. Herein, we aimed to explore the appropriateness of TACE in patients with HCC and EHM in an era of advanced systemic therapy. Methods: This study analyzed 248 consecutive patients with HCC and EHM (median age, 58.5 years; male, 83.5%; Child-Pugh A, 88.7%) who received TACE or systemic therapy (83 sorafenib, 49 lenvatinib, 28 immunotherapy-based) between January 2018 and January 2021. Results: Among the patients, 196 deaths were recorded during a median follow-up of 8.9 months. Patients who received systemic therapy had a higher albumin-bilirubin grade, elevated tumor markers, an increased number of intrahepatic tumors, larger-sized tumors, and more frequent portal vein invasion than those who underwent TACE. TACE was associated with longer median overall survival (OS) than sorafenib (15.1 vs. 4.7 months; 95% confidence interval [CI], 11.1-22.2 vs. 3.7-7.3; hazard ratio [HR], 1.97; P<0.001). After adjustment for potential confounders, TACE was associated with statistically similar survival outcomes to those of lenvatinib (median OS, 8.0 months; 95% CI, 6.5-11.0; HR, 1.21; P=0.411) and immunotherapies (median OS, 14.3 months; 95% CI, 9.5-27.0; HR, 1.01; P=0.973), demonstrating survival benefits equivalent to these treatments. Conclusions In patients with HCC and EHM, TACE can provide a survival benefit comparable to that of newer systemic therapies. Accordingly, TACE remains a valuable option in this era of new systemic therapies.