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1.  Efficacy and safety of solifenacin succinate in Korean patients with overactive bladder: a randomised, prospective, double-blind, multicentre study 
Purpose:
We assessed the efficacy and safety of solifenacin compared with tolterodine for treatment of overactive bladder (OAB) in Korean patients.
Materials and methods:
The study was randomised, double-blind, tolterodine-controlled trial in Korea. Patients had average frequency of ≥ 8 voids per 24 h and episodes of urgency or urgency incontinence ≥ 3 during 3-day voiding diary period. Patients were randomised to 12-week double-blind treatment with either tolterodine immediate release (IR) 2 mg twice daily (TOL4) or solifenacin 5 mg (SOL5) or 10 mg (SOL10) once daily. The outcome measure was mean change in daily micturition frequency, volume, daily frequency of urgency incontinence, urgency and nocturia from baseline to week 12. Quality of life was assessed using the King’s Health Questionnaire.
Results:
A total of 357 were randomised and 329 were evaluated for efficacy. All voiding parameters recorded in micturition diary improved after treatment in all three groups. Mean changes in volume voided were 19.30 ml (26.69%) in TOL4, 30.37 ml (25.89%) in SOL5 and 37.12 ml (33.36%) in SOL10 group (p = 0.03). Speed of onset of SOL10 efficacy on urgency incontinence was faster than that of SOL5 and TOL4. Quality of life improved in all three groups. Dry mouth was the most common adverse event; its incidence was the lowest in SOL5 group (7.63%, compared with 19.49% and 18.64% in SOL10 and TOL4 groups respectively).
Conclusions:
Solifenacin succinate 5 and 10 mg once daily improve OAB symptoms with acceptable tolerability levels compared with tolterodine IR 4 mg. Solifenacin 5 mg is a recommended starting dose in Korean patients with OAB.
doi:10.1111/j.1742-1241.2008.01898.x
PMCID: PMC2680337  PMID: 19143854
2.  Selective inhibition of TNF-α-induced activation of mitogen-activated protein kinases and metastatic activities by gefitinib 
British Journal of Cancer  2005;92(9):1690-1695.
We have reported that the selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib (‘Iressa', ZD1839), suppressed intrahepatic metastasis of hepatocellular carcinoma CBO140C12 cells. In this study, we focused on the tumour necrosis factor-α (TNF-α) signalling pathways. Real-time reverse transcription–polymerase chain reaction showed that TNF-α mRNA was expressed in large quantities in the implanted tumour. Gefitinib inhibited EGF- but not hepatocyte growth factor (HGF)-induced activation of mitogen-activated protein kinase (MAPK) cascades, suggesting selectivity of the inhibitor. However, gefitinib inhibited the TNF-α-induced activation of MAPKs and Akt. In addition, TNF-α-induced metastatic properties including adhesion to fibronectin, mRNA expression of integrin αv, production of matrix metalloproteinase-9 and invasion were inhibited by gefitinib without affecting cell proliferation. Furthermore, the TNF-α-induced responses except for NF-κB activation were blocked by metalloprotease inhibitors, suggesting that gefitinib inhibited the transactivation of EGFR induced by TNF-α. These results suggest that the TNF-α signalling pathway is a possible target of gefitinib in suppressing the intrahepatic metastasis of hepatocellular carcinoma.
doi:10.1038/sj.bjc.6602548
PMCID: PMC2362047  PMID: 15841081
gefitinib; tumour necrosis factor alpha; epidermal growth factor; hepatocellular carcinoma; signalling pathways; metastases
3.  A case of spontaneous cervical and mediastinal emphysema. 
Journal of Korean Medical Science  1998;13(2):223-226.
Subcutaneous cervical and mediastinal emphysema usually can occurs as a result of surgery or trauma. Spontaneous cervical subcutaneous emphysema and pneumomediastinum, occurring in the absence of previous disorders or provocating factors, is very rare. The following case report of spontaneous cervical and mediastinal emphysema is assumed to be the first of its kind in Korea. The patient has been followed up for three years without recurrence or sequelae.
PMCID: PMC3054475  PMID: 9610628
4.  Central obesity, insulin resistance, syndrome X, lipoprotein(a), and cardiovascular risk in Indians, Malays, and Chinese in Singapore. 
STUDY OBJECTIVE: To examine the hypothesis that the higher rates of coronary heart disease (CHD) in Indians (South Asians) compared with Malays and Chinese is at least partly explained by central obesity, insulin resistance, and syndrome X (including possible components). DESIGN: Cross sectional study of the general population. SETTING: Singapore. PARTICIPANTS: Random sample of 961 men and women (Indians, Malays, and Chinese) aged 30 to 69 years. MAIN RESULTS: Fasting serum insulin concentration was correlated directly and strongly with body mass index (BMI), waist-hip ratio (WHR), and abdominal diameter. The fasting insulin concentration was correlated inversely with HDL cholesterol and directly with the fasting triglyceride concentration, blood pressures, plasminogen activator inhibitor 1 (PAI-1), and tissue plasminogen activator (tPA), but it was not correlated with LDL cholesterol, apolipoproteins B and A1, lipoprotein(a), (Lp(a)), fibrinogen, factor VIIc, or prothrombin fragment (F)1 + 2. This indicates that the former but not the latter are part of syndrome X. While Malays had the highest BMI, Indians had a higher WHR (men 0.93 and women 0.84) than Malays (men 0.91 and women 0.82) and Chinese (men 0.91 and women 0.82). In addition, Indians had higher fasting insulin values and more glucose intolerance than Malays and Chinese. Indians had lower HDL cholesterol, and higher PAI-1, tPA, and Lp(a), but not higher LDL cholesterol, fasting triglyceride, blood pressures, fibrinogen, factor VIIc, or prothrombin F1 + 2. CONCLUSIONS: Indians are more prone than Malays or Chinese to central obesity with insulin resistance and glucose intolerance and there are no apparent environmental reasons for this in Singapore. As a consequence, Indians develop some but not all of the features of syndrome X. They also have higher Lp(a) values. All this puts Indians at increased risk of atherosclerosis and thrombosis and must be at least part of the explanation for their higher rates of CHD.
PMCID: PMC1060508  PMID: 9328546
5.  U waves in ventricular hypertrophy: possible demonstration of mechano-electrical feedback. 
British Heart Journal  1986;55(5):428-433.
The relation between ventricular function and electrocardiographic evidence of hypertrophy (by voltage criteria, "strain", and U wave inversion) was examined by means of M mode echocardiography and apex cardiography in 73 patients with diseases associated with left ventricular hypertrophy and 10 normal volunteers. In patients with disease, left ventricular cavity dimension and fractional shortening were unrelated to electrocardiographic findings, but left ventricular posterior wall thickness was greater in those with strain or U wave inversion. Without U wave inversion, hypertrophy and strain were weakly related to diastolic abnormalities, but the addition of U wave inversion was strongly associated with a reduced rate of early diastolic posterior wall thinning, prolonged isovolumic relaxation time, delayed mitral valve opening after minimum cavity dimension, and a pronounced increase in transverse dimension during the isovolumic period suggesting incoordinate relaxation. It is concluded that, whereas a negative U wave frequently occurs in association with the pattern of left ventricular hypertrophy or strain, it alone is strongly related to abnormalities of isovolumic relaxation. The close relation between incoordinate relaxation and U wave inversion, events which occur virtually simultaneously during the isovolumic period, suggests a mechanical influence on U wave genesis.
PMCID: PMC1216376  PMID: 2939860
7.  Haemodynamic response to intravenous hydralazine in patients with pulmonary hypertension. 
British Heart Journal  1983;50(6):579-585.
The acute pulmonary and systemic haemodynamic response to low (0.15 mg/kg) and high (0.30 mg/kg) doses of intravenous hydralazine was evaluated in 26 consecutive patients with severe pulmonary hypertension due to cor pulmonale (nine patients), primary pulmonary hypertension (11 patients), or pulmonary embolism (six patients). Hydralazine did not cause a significant change in pulmonary arterial resistance or pressure in any group but produced a significant reduction in systemic resistance, which correlated with plasma concentration, and a significant increase in pulmonary blood flow index in all groups. Ten patients who experienced a reduction in pulmonary arterial resistance of at least 5 U X m2 after administration of hydralazine had higher initial values for pulmonary arterial resistance and systemic resistance and a lower pulmonary blood flow index than those who did not respond. Maintenance oral hydralazine treatment during nine to 36 months of follow up did not seem to affect symptoms or mortality. These results indicate that hydralazine has limited value in acutely reducing pulmonary arterial pressure or affecting clinical outcome in patients with pulmonary hypertension.
PMCID: PMC481463  PMID: 6652000
8.  Effects of flexible-dose fesoterodine on overactive bladder symptoms and treatment satisfaction: an open-label study 
Aims:
To evaluate the efficacy and tolerability of flexible-dose fesoterodine in subjects with overactive bladder (OAB) who were dissatisfied with previous tolterodine treatment.
Methods:
This was a 12-week, open-label, flexible-dose study of adults with OAB (≥ 8 micturitions and ≥ 3 urgency episodes per 24 h) who had been treated with tolterodine (immediate- or extended-release) for OAB within 2 years of screening and reported dissatisfaction with tolterodine treatment. Subjects received fesoterodine 4 mg once daily for 4 weeks; thereafter, daily dosage was maintained at 4 mg or increased to 8 mg based on the subject’s and physician’s subjective assessment of efficacy and tolerability. Subjects completed 5-day diaries, the Patient Perception of Bladder Condition (PPBC) and the Overactive Bladder Questionnaire (OAB-q) at baseline and week 12 and rated treatment satisfaction at week 12 using the Treatment Satisfaction Question (TSQ). Safety and tolerability were assessed.
Results:
Among 516 subjects treated, approximately 50% opted for dose escalation to 8 mg at week 4. Significant improvements from baseline to week 12 were observed in micturitions, urgency urinary incontinence episodes, micturition-related urgency episodes and severe micturition-related urgency episodes per 24 h (all p< 0.0001). Approximately 80% of subjects who responded to the TSQ at week 12 reported satisfaction with treatment; 38% reported being very satisfied. Using the PPBC, 83% of subjects reported improvement at week 12 with 59% reporting improvement ≥ 2 points. Significant improvements from baseline (p< 0.0001) exceeding the minimally important difference (10 points) were observed in OAB-q Symptom Bother and Health-Related Quality of Life (HRQL) scales and all four HRQL domains. Dry mouth (23%) and constipation (5%) were the most common adverse events; no safety issues were identified.
Conclusion:
Flexible-dose fesoterodine significantly improved OAB symptoms, HRQL, and rates of treatment satisfaction and was well tolerated in subjects with OAB who were dissatisfied with prior tolterodine therapy.
doi:10.1111/j.1742-1241.2009.02035.x
PMCID: PMC2705818  PMID: 19348029

Results 1-8 (8)