Progression of Device-Detected Subclinical Atrial Fibrillation and the Risk of Heart Failure.

BACKGROUND: Long-term continuous monitoring detects short-lasting, subclinical atrial fibrillation (SCAF) in approximately one-third of older individuals with cardiovascular conditions. The relationship between SCAF, its progression, and the development of heart failure (HF) is unclear. OBJECTIVES: This study examined the relationship between progression from shorter to longer SCAF episodes and HF hospitalization. METHODS: Subjects in ASSERT (Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial) were ≥65 years old, had history of hypertension, no prior clinical AF, and an implanted pacemaker or defibrillator. We examined patients whose longest SCAF episode during the first year after enrollment was >6 min but ≤24 h (n = 415). Using time-dependent Cox models, we evaluated the relationship between subsequent development of SCAF >24 h or clinical AF and HF hospitalization. RESULTS: Over a mean follow-up of 2 years, 65 patients (15.7%) progressed to having SCAF episodes >24 h or clinical AF (incidence 8.8% per year). Older age, greater body mass index, and longer SCAF duration within the first year were independent predictors of SCAF progression. The rate of HF hospitalization among patients with SCAF progression was 8.9% per year compared with 2.5% per year for those without progression. After multivariable adjustment, SCAF progression was independently associated with HF hospitalization (hazard ratio [HR]: 4.58; 95% confidence interval [CI]: 1.64 to 12.80; p = 0.004). Similar results were observed when we excluded patients with prior history of HF (HR: 7.06; 95% CI: 1.82 to 27.30; p = 0.005) or when SCAF progression was defined as development of SCAF >24 h alone (HR: 3.68; 95% CI: 1.27 to 10.70; p = 0.016). CONCLUSIONS: In patients with a pacemaker or defibrillator, SCAF progression was strongly associated with HF hospitalization.

2016 Consensus statement on prevention of atherosclerotic cardiovascular disease in the Hong Kong population.

INTRODUCTION: In Hong Kong, the prevalence of atherosclerotic cardiovascular disease has increased markedly over the past few decades, and further increases are expected. In 2008, the Hong Kong Cardiovascular Task Force released a consensus statement on preventing cardiovascular disease in the Hong Kong population. The present article provides an update on these recommendations. PARTICIPANTS: A multidisciplinary group of clinicians comprising the Hong Kong Cardiovascular Task Force-10 cardiologists, an endocrinologist, and a family physician-met in September 2014 and June 2015 in Hong Kong. EVIDENCE: Guidelines from the American College of Cardiology/American Heart Association, the European Society of Hypertension/European Society of Cardiology, and the Eighth Joint National Committee for the Management of High Blood Pressure were reviewed. CONSENSUS PROCESS: Group members reviewed the 2008 Consensus Statement and relevant international guidelines. At the meetings, each topical recommendation of the 2008 Statement was assessed against the pooled recommendations on that topic from the international guidelines. A final recommendation on each topic was generated by consensus after discussion. CONCLUSIONS: It is recommended that a formal risk scoring system should be used for risk assessment of all adults aged 40 years or older who have at least one cardiovascular risk factor. Individuals can be classified as having a low, moderate, or high risk of developing atherosclerotic cardiovascular disease, and appropriate interventions selected accordingly. Recommended lifestyle modifications include adopting a healthy eating pattern; maintaining a low body mass index; quitting smoking; and undertaking regular, moderate-intensity physical activity. Pharmacological interventions should be selected as appropriate after lifestyle modification.

Prospective observational study of isoflavone and the risk of stroke recurrence: potential clinical implications beyond vascular function.

BACKGROUND: Whether isoflavone has any effect on recurrent cardiovascular events is unknown. OBJECTIVE: To investigate the relations between isoflavone intake and the risk of stroke recurrence. SUBJECTS AND METHODS: We recruited 127 consecutive patients with prior history of atherothrombotic/ hemorrhagic stroke (mean age: 67 ± 11 years, 69% male) and prospectively followed up for a mean duration of 30 months. Stroke recurrence and major adverse cardiovascular events (MACE) were documented. Brachial flow-mediated dilatation (FMD) was measured using high-resolution ultrasound. Isoflavone intake was estimated using a validated food frequency questionnaire. RESULTS: Median isoflavone intake was 6.9 (range: 2.1 - 14.5) mg/day. Isoflavone intake was independently associated with increased FMD (Pearson R=0.23, p=0.012). At 30 months, there were 10 stroke recurrence and 12 MACE. Kaplan-Meier analysis showed that patients with isoflavone intake higher than median value had significantly longer median stroke recurrence-free survival time (19.0 [range: 10.4 - 27.6] mth versus 5.0 [range: 4.1 - 5.9] mth, p=0.021) and MACE-free survival time (19.0 [range: 10.4 - 27.6] mth versus 4.0 [range: 2.4 - 5.6] mth, p=0.013). Using multivariate cox regression, higher isoflavone intake was an independent predictor for lower risk of stroke recurrence (hazards ratio 0.18 [95%CI: 0.03 - 0.95], risk reduction 82%, p=0.043) and MACE (hazards ratio 0.16 [95%CI: 0.03 - 0.84], risk reduction 84%, p=0.030). CONCLUSIONS: Higher isoflavone intake in stroke patients was associated with prolonged recurrence-free survival, and reduced risk of stroke recurrence and MACE independent of baseline vascular function. Whether isoflavone may confer clinically significant secondary protection in stroke patients should be further investigated in a randomized controlled trial.

Effects of Radix Astragali and Radix Rehmanniae, the components of an anti-diabetic foot ulcer herbal formula, on metabolism of model CYP1A2, CYP2C9, CYP2D6, CYP2E1 and CYP3A4 probe substrates in pooled human liver microsomes and specific CYP isoforms.

The present study investigated the effects of Radix Astragali (RA) and Radix Rehmanniae (RR), the major components of an anti-diabetic foot ulcer herbal formula (NF3), on the metabolism of model probe substrates of human CYP isoforms, CYP1A2, CYP2C9, CYP2D6, CYP2E1 and CYP3A4, which are important in the metabolism of a variety of xenobiotics. The effects of RA or RR on human CYP1A2 (phenacetin O-deethylase), CYP2C9 (tolbutamide 4-hydroxylase), CYP2D6 (dextromethorphan O-demethylase), CYP2E1 (chlorzoxazone 6-hydroxylase) and CYP3A4 (testosterone 6ß-hydroxylase) activities were investigated using pooled human liver microsomes. NF3 competitively inhibited activities of CYP2C9 (IC(50)=0.98mg/ml) and CYP3A4 (IC(50)=0.76mg/ml), with K(i) of 0.67 and 1.0mg/ml, respectively. With specific human CYP2C9 and CYP3A4 isoforms, NF3 competitively inhibited activities of CYP2C9 (IC(50)=0.86mg/ml) and CYP3A4 (IC(50)=0.88mg/ml), with K(i) of 0.57 and 1.6mg/ml, respectively. Studies on RA or RR individually showed that RR was more important in the metabolic interaction with the model CYP probe substrates. RR dose-dependently inhibited the testosterone 6ß-hydroxylation (K(i)=0.33mg/ml) while RA showed only minimal metabolic interaction potential with the model CYP probe substrates studied. This study showed that RR and the NF3 formula are metabolized mainly by CYP2C9 and/or CYP3A4, but weakly by CYP1A2, CYP2D6 and CYP2E1. The relatively high K(i) values of NF3 (for CYP2C9 and CYP3A4 metabolism) and RR (for CYP3A4 metabolism) would suggest a low potential for NF3 to cause herb-drug interaction involving these CYP isoforms.

Subclinical atrial fibrillation and the risk of stroke.

BACKGROUND: One quarter of strokes are of unknown cause, and subclinical atrial fibrillation may be a common etiologic factor. Pacemakers can detect subclinical episodes of rapid atrial rate, which correlate with electrocardiographically documented atrial fibrillation. We evaluated whether subclinical episodes of rapid atrial rate detected by implanted devices were associated with an increased risk of ischemic stroke in patients who did not have other evidence of atrial fibrillation. METHODS: We enrolled 2580 patients, 65 years of age or older, with hypertension and no history of atrial fibrillation, in whom a pacemaker or defibrillator had recently been implanted. We monitored the patients for 3 months to detect subclinical atrial tachyarrhythmias (episodes of atrial rate >190 beats per minute for more than 6 minutes) and followed them for a mean of 2.5 years for the primary outcome of ischemic stroke or systemic embolism. Patients with pacemakers were randomly assigned to receive or not to receive continuous atrial overdrive pacing. RESULTS: By 3 months, subclinical atrial tachyarrhythmias detected by implanted devices had occurred in 261 patients (10.1%). Subclinical atrial tachyarrhythmias were associated with an increased risk of clinical atrial fibrillation (hazard ratio, 5.56; 95% confidence interval [CI], 3.78 to 8.17; P<0.001) and of ischemic stroke or systemic embolism (hazard ratio, 2.49; 95% CI, 1.28 to 4.85; P=0.007). Of 51 patients who had a primary outcome event, 11 had had subclinical atrial tachyarrhythmias detected by 3 months, and none had had clinical atrial fibrillation by 3 months. The population attributable risk of stroke or systemic embolism associated with subclinical atrial tachyarrhythmias was 13%. Subclinical atrial tachyarrhythmias remained predictive of the primary outcome after adjustment for predictors of stroke (hazard ratio, 2.50; 95% CI, 1.28 to 4.89; P=0.008). Continuous atrial overdrive pacing did not prevent atrial fibrillation. CONCLUSIONS: Subclinical atrial tachyarrhythmias, without clinical atrial fibrillation, occurred frequently in patients with pacemakers and were associated with a significantly increased risk of ischemic stroke or systemic embolism. (Funded by St. Jude Medical; ASSERT ClinicalTrials.gov number, NCT00256152.).

Adverse systemic arterial function in patients with selenium deficiency.

BACKGROUND: Experimental studies have shown that selenium is involved in the synthesis of selenoproteins which might contribute to cardiovascular protection. However, the relationship between selenium deficiency and vascular function in clinical context remains unknown. OBJECTIVE: To investigate for any relationship between selenium deficiency and systemic arterial function in patients with high risk of vascular events. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: 306 consecutive patients with high risk for cardiovascular events (coronary artery disease 35%, acute/ recurrent ischemic stroke 40%, diabetes mellitus 54%) followed up at internal medicine outpatient clinics. MEASUREMENTS: Non-invasive brachial-ankle pulse wave velocity (PWV) was determined using vascular profiling system (VP-2000). Long-term intake of selenium was determined by a validated food frequency questionnaire. RESULTS: Mean daily selenium intake was 59.5 ± 52.1 mcg/day, and mean PWV was 1782.4 ± 418.4 cm/s. Patients with selenium intake <10th percentile had significantly higher PWV as compared to patients with intake ≥ 10th percentile (1968.2 ± 648.9 cm/s versus 1762.2 ± 381.6 cm/s, P=0.010). After adjusting for potential confounders including age, gender, history of hypertension, hyperlipidemia, diabetes and cardiovascular disease, smoking status, use of cardiovascular medications, waist-hip ratio, education/ financial status, physical activity, calorie intake and intake of antioxidant vitamins, deficient selenium intake <10th percentile remained independently predictive of increased PWV by +363.4 cm/s [95% CI: 68.1 to 658.6, P=0.016, relative increase 21%]. CONCLUSIONS: Selenium deficiency is associated with adverse arterial function in patients with high risk for vascular events.

Safety and efficacy of oral anticoagulation therapy in Chinese patients with concomitant atrial fibrillation and hypertension.

Limited evidence is available on the safety and efficacy of anticoagulants in non-valvular atrial fibrillation (AF) patients with concomitant hypertension. We investigated the safety and efficacy of 476 consecutive anticoagulated Chinese outpatients with non-valvular AF and hypertension. Occurrence of ischaemic stroke and major bleeding, and international normalized ratio (INR) values during these events were recorded. There was no significant difference in anticoagulation control between patients with or without hypertension. INR-specific incidence rates of the events were calculated, which showed no excessive risk for ischaemic stroke (2.5 vs 1.6% per year, P=0.22) or major bleeding (3.9 vs 3.2% per year, P=0.29) in non-valvular AF patients with or without hypertension. In multivariate analysis, congestive heart failure, smoking and high CHADS2 score were independent predictors for ischaemic stroke, whereas use of antiplatelet agents was an independent predictor for bleeding. It can be noted that hypertension was not associated with ischaemic stroke or major bleeding. Hypertensive patients who achieved target blood pressure control (<130/80 mm Hg) had a lower ischaemic stroke (0.9 vs 3.1% per year, P=0.01), but similar bleeding risk compared with those not achieving target blood pressure. Our findings demonstrate the effects of hypertension on the outcomes of warfarin therapy; further investigation is needed to clarify whether more aggressive antihypertensive therapy could result in better outcomes in hypertensive patients with non-valvular AF.

Inhibition of c-Met downregulates TIGAR expression and reduces NADPH production leading to cell death.

c-Met represents an important emerging therapeutic target in cancer. In this study, we demonstrate the mechanism by which c-Met tyrosine kinase inhibition inhibits tumor growth in a highly invasive Asian-prevalent head and neck cancer, nasopharyngeal cancer (NPC). c-Met tyrosine kinase inhibitors (TKIs; AM7 and c-Met TKI tool compound SU11274) downregulated c-Met phosphorylation, resulting in marked inhibition of NPC cell growth and invasion. Strikingly, inhibition of c-Met resulted in significant downregulation of TP53-induced Glycolysis and Apoptosis Regulator (TIGAR) and subsequent depletion of intracellular NADPH. Importantly, overexpression of TIGAR ameliorated the effects of c-Met kinase inhibition, confirming the importance of TIGAR downregulation in the growth inhibitory activity of c-Met TKI. The effects of c-Met inhibition on TIGAR and NADPH levels were observed with two different c-Met TKIs (AM7 and SU11274) and with multiple cell lines. As NADPH provides a crucial reducing power required for cell survival and proliferation, our findings reveal a novel mechanistic action of c-Met TKI, which may represent a key effect of c-Met kinase inhibition. Our data provide the first evidence linking c-Met, TIGAR and NADPH regulation in human cancer cells suggesting that inhibition of a tyrosine kinase/TIGAR/NADPH cascade may have therapeutic applicability in human cancers.

FGF8b oncogene mediates proliferation and invasion of Epstein-Barr virus-associated nasopharyngeal carcinoma cells: implication for viral-mediated FGF8b upregulation.

The fibroblast growth factor 8b (FGF8b) oncogene is known to be primarily involved in the tumorigenesis and progression of hormone-related cancers. Its role in other epithelial cancers has not been investigated, except for esophageal cancer, in which FGF8b overexpression was mainly found in tumor biopsies of male patients. These observations were consistent with previous findings in these cancer types that the male sex-hormone androgen is responsible for FGF8b expression. Nasopharyngeal carcinoma (NPC) is a highly metastatic cancer of head and neck commonly found in Asia. It is etiologically associated with Epstein-Barr Virus (EBV) infection, inflammatory tumor microenvironment and relatively higher male predominance. Here, we reported for the first time that FGF8b is overexpressed in this EBV-associated non-hormone-related cancer of the head and neck, NPC. More importantly, overexpression of FGF8b mRNA and protein was detected in a large majority of NPC tumors from both male and female genders, in addition to multiple NPC cell lines. We hypothesized that FGF8b overexpression may contribute to NPC tumorigenesis. Using EBV-associated NPC cell lines, we demonstrated that specific knockdown of FGF8b by small interfering RNA inhibited cell proliferation, migration and invasion, whereas exogenous FGF8b stimulated these multiple phenotypes. Further mechanistic investigation revealed that in addition to NF-κB signaling (a major inflammatory signaling pathway known to be activated in NPC), an important EBV oncoprotein, the latent membrane protein 1 (LMP1), was found to be a direct inducer of FGF8b overexpression in NPC cells, whereas androgen (testosterone) has minimal effect on FGF8b expression in EBV-associated NPC cells. In summary, our study has identified LMP1 as the first viral oncogene capable of directly inducing FGF8b (an important cellular oncogene) expression in human cancer cells. This novel mechanism of viral-mediated FGF8 upregulation may implicate a new role of oncoviruses in human carcinogenesis.

Fish-oil supplement has neutral effects on vascular and metabolic function but improves renal function in patients with Type 2 diabetes mellitus.

AIMS: Increased dietary fish-oil consumption is associated with a reduced risk of coronary heart events and has pronounced effects on dyslipidaemia. However, the effects of fish-oil supplement on vascular function and metabolic profile in patients with Type 2 diabetes mellitus (DM) are unclear. METHODS: In a double-blind placebo-controlled trial, we randomized 97 Type 2 DM patients without prior cardiovascular disease to fish-oil (4 g/day, n = 49) or olive-oil (with equivalent calories, as placebo, n = 48) supplements for 12 weeks. Assessment of vascular function with brachial artery flow-mediated dilation (FMD) and circulating levels of endothelial progenitor cells (EPCs), and metabolic parameters, high-sensitivity C-reactive protein (hsCRP), oxidative stress markers and renal function were examined before and after the supplement. RESULTS: Despite a significant reduction in serum triglycerides (-0.47 mmol/l, P < 0.01), 12-week supplement of fish oil did not improve vascular function as determined by FMD (+0.16%, P = 0.83) and circulating EPC count (+4 cells/microl, P = 0.78). Furthermore, fish-oil supplement did not have any significant treatment effects on hsCRP, oxidative stress, low- and high-density lipoprotein and glycated haemoglobin (HbA(1c)) (all P > 0.05). In contrast, serum creatinine was lower (-4.5 micromol/l, P = 0.01) in fish-oil-treated patients as compared with control subjects. CONCLUSIONS: This study demonstrated that 12 weeks of fish-oil supplement had no significant beneficial effect on vascular endothelial function, but improved renal function without changes in endothelial function, metabolic profiles, blood pressure, inflammation or oxidative stress in patients with Type 2 DM.

Predictors of inhospital outcome after acute inferior wall myocardial infarction.

INTRODUCTION: Compared with anterior wall myocardial infarction, inferior wall myocardial infarction is generally regarded as being low risk. The aim of this study was to elucidate the clinical factors affecting its inhospital outcome. METHODS: From January 1997 to March 2006, 546 consecutive patients who suffered from their first inferior wall myocardial infarction were recruited for the study. The demographic, clinical, electrocardiographical and angiographical characteristics, treatment and medications, complications and inhospital deaths were subjected to univariate analysis. The factors that had a p-value of less than 0.1 were included for multivariate logistic regression analysis. A p-value of less than 0.05 was considered significant. The impact of thrombolysis on clinical outcome in various high-risk patient subsets was also examined. RESULTS: An advanced age of more than 74 years, female gender, lateral wall extension, complete atrioventricular block, bundle branch block, and cardiac free-wall rupture were found to be independent predictors of inhospital mortality, whereas the use of thrombolysis was associated with a favourable outcome. On the other hand, right ventricular infarction and precordial ST-segment depression are not predictive of poor outcome. In addition, thrombolysis reduced inhospital mortality in patients with an age above 64 years, male gender, lateral wall extension, haemodynamically-significant right ventricular infarction and complete atrioventricular block. CONCLUSION: In inferior wall myocardial infarction, independent predictors of poor inhospital outcome are advanced age, female gender, lateral wall extension, complete atrioventricular block, bundle branch block and cardiac free-wall rupture. The use of thrombolysis is generally beneficial, especially in those of the high-risk subsets.

Prevalence and extent of calcification over aorta, coronary and carotid arteries in patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the prevalence and pattern of arterial calcification in patients with rheumatoid arthritis (RA). BACKGROUND: Patients with RA are prone to premature atherosclerosis; nonetheless the prevalence and extent of atherosclerosis in different vascular beds and their relationship to each other remain unknown. METHODS: We studied the distribution and extent of arterial calcification in 85 RA patients and 85 age-and sex-matched controls. Arterial calcification as determined by calcium score (CS) were measured using multi-detector computed tomography in thoracic aorta, coronary and carotid arteries. RESULTS: Compared with controls, RA patients had a significantly higher average CS and prevalence of CS > 0 in aorta, coronary and carotid arteries and overall arteries (all P < 0.05). After adjusting for age and sex, RA patients had a significantly higher relative risk of developing calcification in the aorta [Odds Ratio (OR) = 19.5, 95% Confidence Interval (CI): 8.0-47.6], followed by the carotid arteries (OR = 5.7, 95% CI:1.7-18.7) and coronary arteries (OR = 5.0, 95% CI:2.2-11.1) compared with controls (all P < 0.01). Amongst RA patients aged >60, 90% had diffuse arterial calcification, especially over the thoracic aorta, compared with 55% of controls who had arterial calcification clustered in the coronary arteries (P < 0.05). RA patients with total CS > 0 were older with a higher urea level and C-reactive protein than those without arterial calcification, no factor was found to be independently predictive for arterial calcification (all P > 0.05). CONCLUSIONS: Our results demonstrated that RA patients had earlier onset, more diffuse arterial calcification over multiple vascular beds and more preferential involvement of thoracic aorta, rather than coronary artery when compared with control.

Radix Astragali and Radix Rehmanniae, the principal components of two antidiabetic foot ulcer herbal formulae, elicit viability-promoting effects on primary fibroblasts cultured from diabetic foot ulcer tissues.

Over 194 million people suffer from diabetes worldwide. The improper control of diabetes may result in diabetic foot ulcer or even amputation. Herbal medicine provides a means for treating diabetic foot ulcers for a large population in developing countries. The wound healing-enhancing activities of the principal herbs, Radix Astragali (RA) and Radix Rehmanniae (RR) in two clinically efficacious Chinese herbal formulae were studied in primary fibroblasts from diabetic foot ulcer patients. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that RA and RR significantly enhanced the viability of fibroblasts isolated from foot ulcers of diabetic patients, even from those with no response to insulin treatment. The results in this study indicate that fibroblast viability enhancement effects of RA and RR likely underlie the healing effects of F1 and F2 in diabetic foot ulcers.

A randomized comparison of sirolimus-eluting versus bare metal stents in the treatment of diabetic patients with native coronary artery lesions: the DECODE study.

OBJECTIVE: To compare the effects of sirolimus-eluting (SES) versus bare metal stents (BMS) on 6-month in-stent late luminal loss (LLL) and 1-year major adverse cardiac events (MACE) in diabetics undergoing percutaneous coronary interventions. BACKGROUND: In studies of unselected patients, coronary restenosis rates have been lower with SES than with BMS. Comparisons of SES versus BMS in diabetics with more than one stenosis or more than one vessel disease are few. METHODS: This open-label trial randomly assigned 200 diabetics with de novo coronary artery stenoses to receive up to three SES versus BMS in a 2:1 ratio. The patients underwent repeat coronary angiography at 6 months after the index procedure and were followed-up for 1 year. The primary study endpoint was in-stent LLL at 6 months. RESULTS: Between August 2002 and May 2004, 83 patients (mean age = 60 years) with 128 lesions (mean = 1.5 per patient) were enrolled at four U.S. and seven Asian medical centers. Enrollment was terminated early by the Safety Monitoring Board because of a statistically significant difference in rates of clinical endpoints. The mean in-stent LLL at 6 months was 0.23 mm in SES versus 1.10 mm in BMS recipients (P < 0.001). At 12 months, 8 patients (15%) assigned to SES had experienced MACE versus 12 patients (41%) assigned to BMS (P = 0.006). CONCLUSIONS: In diabetics, the mean 6-month in-stent LLL was significantly smaller, and 12-month MACE rate significantly lower, after myocardial revascularization with SES than with BMS.

An evaluation of the psychometric properties of the Smoking Self-Efficacy Questionnaire (SEQ-12) among Chinese cardiac patients who smoke.

Smoking cessation can reduce both morbidity and mortality among patients who have heart disease. China has the largest number of smokers in the world, and most smokers have low motivation to quit. Regular smoking cessation services are almost nonexistent in China, and little is known about the psychometric properties of instruments in assessing smoking self-efficacy in Chinese, whose cultures differ greatly from those of Westerners. The present study tested the psychometric properties of the Chinese version of the Smoking Self-Efficacy Questionnaire (SEQ-12) among 1,841 Chinese smokers who had heart disease, including (a) factorial structure using confirmatory factor analysis, (b) reliability with Cronbach's alpha, (c) concurrent validity, and (d) predictive validity of successful quitting. Confirmatory factor analysis of the SEQ-12 revealed a modified two-factor model that provided a good fit to the data; item 6 ("urge to smoke") was an indicator for the external stimuli subscale rather than for the internal stimuli subscale. Internal consistency coefficients (.77 for external stimuli and .88 for internal stimuli) were acceptable. Baseline self-efficacy scores were significantly associated positively with stage of readiness to quit, and negatively with cigarettes smoked per day and Fagerstrom Test for Nicotine Dependence (FTND) score. Multivariate logistic regression analysis showed that successful quitting at 1 month and at 3 months were predicted by higher external stimuli score, fewer cigarettes smoked per day, lower FTND scores, and being in the intervention group. We concluded that the Chinese version of the SEQ-12 is a valid and reliable instrument for Chinese cardiac patients who smoke. The SEQ-12 can be used to assess smokers' self-efficacy so that appropriate smoking cessation interventions can be provided.

The 5-HT2 antagonist ketanserin is an open channel blocker of human cardiac ether-à-go-go-related gene (hERG) potassium channels.

BACKGROUND AND PURPOSE: Ketanserin, a selective 5-HT receptor antagonist, prolongs the QT interval of ECG in patients. The purpose of the present study was to determine whether ketanserin would block human cardiac ether-à-go-go-related gene (hERG) potassium channels. EXPERIMENTAL APPROACH: Whole-cell patch voltage-clamp technique was used to record membrane currents in HEK 293 cells expressing wild type or mutant hERG channel genes. KEY RESULTS: Ketanserin blocked hERG current (I(hERG)) in a concentration-dependent manner (IC50=0.11 microM). The drug showed an open channel blocking property, the block increasing significantly at depolarizing voltages between +10 to +60 mV. Voltage-dependence for inactivation of hERG channels was negatively shifted by 0.3 microM ketanserin. A 2.8 fold attenuation of inhibition by elevation of external K+ concentration (from 5.0 to 20 mM) was observed, whereas the inactivation-deficient mutants S620T and S631A had the IC50s of 0.84 +/- 0.2 and 1.7 +/-0.4 microM (7.6 and 15.4 fold attenuation of block). In addition, the hERG mutants in pore helix and S6 also significantly reduced the channel block (2-59 fold) by ketanserin. CONCLUSIONS AND IMPLICATIONS: These results suggest that ketanserin binds to and blocks the open hERG channels in the pore helix and the S6 domain; channel inactivation is also involved in the blockade of hERG channels. Blockade of hERG channels most likely contributes to the prolongation of QT intervals in ECG observed clinically at therapeutic concentrations of ketanserin.

Caecal metastasis from a primary small-cell lung carcinoma.

Small bowel metastases from a primary lung carcinoma are rare. We report a case of a 59-year-old male with a primary small-cell lung carcinoma who developed anaemia and bowel symptoms. On colonoscopic examination he was found to have a tumour in the caecum near the ileocaecal valve, which was biopsied, revealing small neuroendocrine tumour cells. The patient then underwent systemic chemotherapy, which achieved a reduction in the size of the primary lung tumour and an improvement in his bowel symptoms. It is important that such a rare condition be recognised early as complicated intestinal metastases from a lung carcinoma can lead to high mortality rates and poor short-term outcome. With advances in chemotherapy and palliative care, patients with metastatic lung carcinoma can sometimes survive more than a year with reasonable quality of life.