Jun-Ting Liou

Risk of stroke associated with inhaled ipratropium bromide in chronic obstructive pulmonary disease: A population-based nested case–control study

BACKGROUND Cardiovascular safety concerns about inhaled ipratropium bromide have recently been raised. Nonetheless, the specific stroke risk associated with ipratropium use has not been evaluated thoroughly. METHODS This was a population-based nested case-control study analyzing data from the National Health Insurance Research Database in Taiwan. A cohort of 15,396 newly-diagnosed chronic obstructive pulmonary disease (COPD) patients was included between 2001 and 2007, in which 1477 cases of incident hospitalization for stroke were identified. Each case was individually matched to four randomly-selected controls based on age, sex, and cohort entry date. Conditional logistic regressions were used to estimate the odds ratio (OR) for risk of stroke-related hospitalization associated with ipratropium use. RESULTS Any use of ipratropium within the 6 months before the index date was associated with an increased risk of stroke compared with nonuse (adjusted OR, 2.02; 95% CI, 1.71 to 2.41). The observed risk remained significant regardless of accumulated doses. Additionally, use of ipratropium within 30 days before the index date resulted in the greatest risk (adjusted OR, 2.97 95% CI, 2.27 to 3.88). Furthermore, an increased risk of stroke was found for ipratropium regimens involving concomitant use of inhaled short-acting β(2)-agonists (SABAs; adjusted OR, 2.18; 95% CI, 1.81 to 2.62) or theophyllines (adjusted OR, 1.79; 95% CI, 1.42 to 2.26). CONCLUSIONS Use of ipratropium is associated with an increased risk of stroke in COPD patients. Clinicians should be alert to that risk when prescribing ipratropium, especially for those receiving ipratropium more recently or those with concomitant use of SABAs or theophyllines.

Modulation of human T cells signaling transduction by lovastatin

Statins are applied clinically to treat hypercholesterolemia and proposed to have some kinds of anti-inflammatory properties for reducing the incidence of atherosclerosis-related cardiovascular events. However, it was rarely known about statins on the signal transduction on human primary T cells. To gain insight into the mechanism of statins on human T cells, we investigated the effects of both lovastatin and atorvastatin on activated human primary T cells. The human primary T cells from the blood of normal human beings were isolated. We found that lovastatin, but not atorvastatin, can dose-dependently inhibit cytokine production such as interleukin-2, interleukin-4, and interferon-gamma from activated human T cells. Neither lovastatin nor atorvastatin can regulate the TNF-alpha production on both activated human T cells and monocytes. Molecular investigation was performed that lovastatin, but not atorvastatin, could down-regulate both activator protein-1 and NF-kappaB DNA binding activities, assessed by electrophoretic mobility shift assay. Our observations may extend potential and differential therapeutic mechanisms of lovastatin with cell-mediated capacity to prevent or treat some of inflammation related diseases.

JNK/AP-1 activation contributes to tetrandrine resistance in T-cell acute lymphoblastic leukaemia

T-cell acute lymphoblastic leukaemia (T-ALL) is a challenging malignancy with a high relapse rate attributed to drug resistance. Tetrandrine (TET), a bisbenzylisoquinoline alkaloid extracted from a Chinese herb, is a potential anti-cancer and anti-leukaemic drug. In this study we investigated the mechanisms of TET resistance in T-ALL cells in vitro. Among the four T-ALL cell lines tested, Jurkat and CEM cells exhibited the lowest and highest resistance to TET with IC50 values at 24 h of 4.31±0.12 and 16.53±3.32 μmol/L, respectively. When treated with TET, the activity of transcription factor activator protein 1 (AP-1) was significantly decreased in Jurkat cells but nearly constant in CEM cells. To avoid cell-specific variation in drug resistance and transcription factor activities, we established a TET-R Jurkat subclone with the estimated IC50 value of 10.90±.92 μmol/L by exposing the cells to increasing concentrations of TET. Interestingly, when treated with TET, TET-R Jurkat cells exhibited enhanced AP-1 and NF-κB activity, along with upregulation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) signaling pathways, whereas the expression of P-gp was not altered. Selective inhibition of JNK but not ERK suppressed AP-1 activity and TET resistance in TET-R Jurkat cells and in CEM cells. These results demonstrate that Jurkat cells acquire TET resistance through activation of the JNK/AP-1 pathway but not through P-gp expression. The JNK/AP-1 pathway may be a potential therapeutic target in relapsed T-ALL.

Evaluation of Stroke Risk Associated with the Use of Typical or Atypical Antipsychotics among Patients with Cardiovascular Diseases

Background: Concerns regarding stroke safety associated with the use of atypical antipsychotics among dementia patients have been raised. Although observational studies have found conflicting associations of stroke risk with the use of typical or atypical antipsychotics among the elderly with or without dementia, patients with cardiovascular diseases (CVDs), a high-risk for the stroke population, have not been examined. Little evidence has been provided regarding comparison of the stroke risk between the two antipsychotic classes. This study aimed to evaluate the comparative stroke risk with atypical versus typical antipsychotic use among CVD patients. Materials and Methods: We conducted a population-based nested case-control study analyzing the Taiwan National Health Insurance Research Database from January 1, 1996 to December 31, 2007. A total of 7,460 CVD patients was followed-up, among which 580 hospitalized cases with stroke were identified and matched to 5,398 randomly selected controls. Conditional logistic regressions were employed to quantify the difference in stroke risk associated with atypical versus typical antipsychotics. Results: Any use and current use of atypical antipsychotics were associated with a 1.67-fold (95% confidence interval [CI], 1.21-2.30) and a 2.30-fold (95% CI, 1.56-3.40) increased risk of stroke relative to any typical antipsychotic use, respectively. The stroke risk associated with current use of atypical antipsychotics persisted even compared with current use of typical antipsychotics (adjusted odds ratio, 1.53; 95% CI, 1.02-2.33). Conclusions: Use of atypical antipsychotics is associated with an increased risk of stroke requiring hospitalization compared to typical antipsychotic use among CVD patients. Healthcare professionals should take this risk into account when choosing between typical and atypical antipsychotic treatments among CVD patients.

Chest Pain with Normal Thallium-201 Myocardial Perfusion Image - Is It Really Normal?

BACKGROUND Thallium-201 myocardial perfusion image (MPI) is commonly used to detect coronary artery disease in patients with chest pain. Although a normal thallium-201 MPI result is generally considered to be a good prognosis and further coronary angiogram is not recommended, there are still a few patients who suffer from unexpected acute coronary events. The aim of this study was to investigate the clinical prognosis in patients with normal thallium-201 MPI. METHODS From January 2006 to August 2012, a total 22,003 patients undergoing thallium-201 MPI in one tertiary center were screened. Of these, 8092 patients had normal results and were investigated retrospectively. During follow-up, 54 patients underwent coronary angiogram because of refractory typical angina pectoris or unexpected acute coronary events. These 54 patients were divided into 2 groups: group I consisted of 26 (48.1%) patients with angiography-proven significant coronary artery stenosis, and group II consisted of 28 (51.9%) patients without significant stenosis. RESULTS Patients in group I had a higher prevalence of prior coronary stenting and electrocardiographic features of ST depression compared with patients in group II. The multivariate analysis demonstrated that both prior coronary stenting and ST depression were risk predictors of unexpected acute coronary events in the patients with normal thallium-201 MPI [odds ratio (OR), 5.93; 95% confidence interval (CI): 1.03-34.06, p = 0.05 and OR, 7.10; 95% CI: 1.28-39.51, p = 0.03,respectively]. CONCLUSIONS Although there is a low incidence of unexpected acute coronary events in patients with chest pain and normal thallium-201 MPI, physicians should be aware of the potentials risk in certain patients in this specific population.

Risk of Coronary Artery Disease in Patients With Traumatic Intracranial Hemorrhage: A Nationwide, Population-Based Cohort Study

AbstractTraumatic intracranial hemorrhage (ICH) is prevalent worldwide with long-term consequences, including disabilities. However, studies on the association of traumatic ICH with coronary artery disease (CAD) are scant. Therefore, this study explored the aforementioned association in a large-scale, population-based cohort.A total of 128,997 patients with newly diagnosed traumatic ICH and 257,994 age- and sex-matched patients without traumatic ICH from 2000 to 2010 were identified from Taiwans National Health Insurance Research Database. The Kaplan–Meier method was used for measuring the cumulative incidence of CAD in each cohort. Cox proportional regression models were used for evaluating the risk of CAD in patients with and without traumatic ICH and for comparing the risk between the 2 cohorts.The Kaplan–Meier analysis revealed that the cumulative incidence curves of CAD were significantly higher in patients with traumatic ICH than in those without ICH (log-rank test, P < 0.001). After adjustment for age, sex, and comorbidities, patients with traumatic ICH were associated with a higher risk of CAD compared with those without traumatic ICH (adjusted hazard ratio = 1.16, 95% confidence interval = 1.13–1.20). Compared with the general population, patients with traumatic ICH and having underlying comorbidities, including diabetes, hypertension, hyperlipidemia, chronic obstructive pulmonary disease, chronic kidney disease, and congestive heart failure, exhibited multiplicative risks of developing CAD.This cohort study revealed an increased risk of CAD in patients with traumatic ICH. Therefore, comprehensive evaluation and aggressive risk reduction for CAD are recommended in these patients.

Clinical and prognostic correlates of ST-elevation myocardial infarction patients with normal coronary angiography

Background: Revascularization within a 90-min door-to-balloon time is a strict policy enacted in Taiwan. Prompt diagnosis is critical to avoid an unnecessary procedure and catheterization laboratory activation. This study was aimed to investigate the clinical and prognostic characteristics of the patients with ST-elevation myocardial infarction (STEMI) referred for primary percutaneous coronary intervention (PCI) and normal coronary arteries found following coronary angiography (CAG). Materials and Methods: From October 2009 to December 2012, 216 consecutive patients with STEMI referred for primary PCI were enrolled. The data of clinical history, physical examination, laboratory results, electrocardiography, echocardiography, CAG findings, diagnosis, and outcomes were collected and analyzed. Results: A total of 17 patients were proved normal coronaries angiographically. The incidence of the conditions mimicking as STEMI is 7.9%. Alternative diagnosis was coronary spasm (n = 7), peri-myocarditis (n = 6), apical ballooning syndrome (n = 3), anaphylactic shock (n = 1). Compared with STEMI group, patients in normal coronaries group were younger, with a less premature family history of coronary artery disease (CAD), and reported angina. The 30-day mortality rate in the normal coronaries group was 5.9%. Conclusions: Cautiously evaluating CAD risk factors and symptoms of angina and awareness of alternative diagnosis are important to make a prompt diagnosis without compromising accuracy in the patients presenting as suspected STEMI.