Association between angiotensin I-converting enzyme gene insertion/deletion polymorphism and risk of rheumatic heart disease

Scarring and collagen deposition in the valves and destruction of myocytes may result from the combined effects of a smoldering rheumatic process and a constant trauma to the mitral valve or aortic valve by the turbulent flow in rheumatic heart disease (RHD). It has been suggested that angiotensin I-converting enzyme (ACE) may be responsible for the increased valvular fibrosis and calcification in the pathogenesis of RHD. However, the role of ACE genetic variant in RHD has not been studied among the Chinese population in Taiwan. Hence, a case-controlled study was carried out to investigate the possible relationship between the ACE gene insertion/deletion (I/D) and G2350A polymorphisms and RHD. A group of 115 patients with RHD documented by echocardiography and 100 age- and sex-matched normal control subjects were studied. ACE gene I/D and G2350A polymorphisms were identified by polymerase chain reaction-based restriction analysis. There was a significant difference in the distribution of ACE I/D genotypes (P = 0.02) and allelic frequencies (P = 0.04) between RHD cases and normal controls. An odds ratio for the risk of RHD associated with the ACE I/D II genotype was 2.12 (95% CI, 1.21-3.71). An odds ratio for the risk of RHD associated with the ACE I allele was 1.50 (95% CI, 1.02-2.21). The ACE G2350A polymorphism showed no association with RHD (P = 0.90). Further categorization of RHD patients into mitral valve disease and combined valve disease subgroups revealed no statistical difference in these gene polymorphisms when compared between the two subgroups. This study shows that patients with RHD have a higher frequency of ACE II genotype and I allele, which supports a role for ACE I/D gene polymorphisms in determining the risk of RHD in Taiwan Chinese.     

Identification of 7,12-dimethylbenz[a]anthracene metabolites that lead to mutagenesis in mammalian cells

The mutagenicity of 7,12-dimethylbenz[a]-anthracene (DMBA) and 11 of its enzymatically derived metabolites was tested with Chinese hamster V79 cells for identification of mutagenic metabolites. The metabolites consisted of 7-hydroxymethyl-12-methylbenz[a]anthracene, 7-methyl-12-hydroxymethylbenz[a]anthracene, 7,12-dihydroxymethylbenz[a]anthracene, three trans-3,4-diols, two trans-5,6-diols, and three trans-8,9-diols, all of which derived from DMBA or from the hydroxymethyl derivatives. Mutations were characterized by resistance to ouabain and 6-thioguanine. None of the tested metabolites were mutagenic in V79 cells, which do not metabolize polycyclic aromatic hydrocarbons. Therefore, mutagenesis in the V79 cells was tested in the presence of golden hamster cells capable of metabolizing polycyclic aromatic hydrocarbons (cell-mediated assay). In this assay, DMBA, 7-hydroxymethyl-12-methylbenz[a]anthracene, 7-methyl-12-hydroxymethylbenz[a]anthracene, and their trans3,4-diols were mutagenic for both genetic markers, and the mutagenic response increased as a function of the hydrocarbon dose. All other metabolites were either inactive or showed up to a 4-fold higher mutation frequency than the untreated V79 cells for ouabain and 6-thioguanine resistance. The DMBA-trans-3,4-diol was the only metabolite that was more active than DMBA itself; at 0.05 muM it was 6-8 times more active than DMBA itself; at 0.05 muM it was 6-8 times more active than DMBA in inducing both ouabain and 6-thioguanine resistance. This diol was mutagenic at a dose as low as 0.01 muM. Mutagenesis by DMBA and the trans-3,4-diols was inhibited by 7,8-benzoflavone, an inhibitor of mixed-function oxidases. Analysis of DMBA metabolism in intact golden hamster cells indicated that DMBA-trans-3,4-diol is one of the major metabolites produced. Our results therefore suggest that DMBA-trans-3,4-diol may be metabolized to a diol-epoxide, presumably the trans-3,4-diol-1,2-epoxide, which may be a major reactive metabolite responsible for DMBA mutagenicity in mammalian cells.     

Estimating medical costs of gastroenterological diseases

AIM: To estimate the direct medical costs of gastroenterological diseases within the universal health insurance program among the population of local residents in Taiwan. METHODS: The data sources were the first 4 cohort datasets of 200,000 people from the National Health Insurance Research Database in Taipei. The ambulatory, inpatient and pharmacy claims of the cohort in 2001 were analyzed. Besides prevalence and medical costs of diseases, both amount and costs of utilization in procedures and drugs were calculated. RESULTS: Of the cohort with 183,976 eligible people, 44.2% had ever a gastroenterological diagnosis during the year. The age group 20-39 years had the lowest prevalence rate (39.2%) while the elderly had the highest (58.4%). The prevalence rate was higher in women than in men (48.5% vs. 40.0%). Totally, 30.4% of 14,888 inpatients had ever a gastroenterological diagnosis at discharge and 18.8% of 51,359 patients at clinics of traditional Chinese medicine had such a diagnosis there. If only the principal diagnosis on each claim was considered, 16.2% of admissions, 8.0% of outpatient visits, and 10.1% of the total medical costs (8,469,909 US dollars/83,830,239 US dollars) were attributed to gastroenterological diseases. On average, 46.0 US dollars per insured person in a year were spent in treating gastroenterological diseases. Diagnostic procedures related to gastroenterological diseases accounted for 24.2% of the costs for all diagnostic procedures and 2.3% of the total medical costs. Therapeutic procedures related to gastroenterological diseases accounted for 4.5% of the costs for all therapeutic procedures and 1.3% of the total medical costs. Drugs related to gastroenterological diseases accounted for 7.3% of the costs for all drugs and 1.9% of the total medical costs. CONCLUSION: Gastroenterological diseases are prevalent among the population of local residents in Taiwan, accounting for a tenth of the total medical costs. Further investigations are needed to differentiate costs in screening, ruling out, confirming, and treating.     

Improvement of Short-Term Outcomes for High-Risk Bleeding Peptic Ulcers With Addition of Argon Plasma Coagulation Following Endoscopic Injection Therapy: A Randomized Controlled Trial

A second endoscopic method together with injection therapy is recommended to treat high-risk bleeding peptic ulcers. This study investigated whether additional argon plasma coagulation (APC) treatment could influence hemostatic efficacy following endoscopic injection therapy to treat high-risk bleeding ulcers.From October 2010 to January 2012, eligible patients with high-risk bleeding ulcers were admitted to our hospital. They prospectively randomly underwent either APC therapy along with distilled water injection or distilled water injection alone. Episodes of rebleeding were retreated with endoscopic combination therapy. Patients in whom retreatment was ineffective underwent emergency surgery or transarterial embolization (TAE).A total of 116 enrolled patients were analyzed. The hemostatic efficacy in 58 patients treated with APC along with distilled water injection was compared with that in 58 patients treated with distilled water injection alone. The 2 treatment groups were similar with respect to all baseline characteristics. Initial hemostasis was accomplished in 56 patients treated with combined therapy, and 55 patients treated with distilled water injection therapy (97% vs 95%, P = 0.648). Bleeding recurred in 2 patients treated with combined therapy, and 9 patients treated with distilled water injection (3.6% vs 16%, P = 0.029). Treatment method was the only independent prognostic factor for recurrent bleeding (odds ratio 0.17; 95% confidence interval 0.03–0.84; P = 0.029). The 2 groups did not differ significantly in hospital stay, TAE, surgery, and mortality.Endoscopic therapy with APC following distilled water injection is more effective than distilled water injection alone for preventing rebleeding of peptic ulcer.     

A Simple Risk Model to Predict Survival in Patients With Carcinoma of Unknown Primary Origin

Carcinoma of unknown primary origin (CUP) is characterized by diverse histological subtypes and clinical presentations, ranging from clinically indolent to frankly aggressive behaviors. This study aimed to identify prognostic factors of CUP and to develop a simple risk model to predict survival in a cohort of Asian patients.We retrospectively reviewed 190 patients diagnosed with CUP between 2007 and 2012 at a single medical center in Taiwan. The clinicopathological parameters and outcomes of our cohort were analyzed. A risk model was developed using multivariate logistic regression and a prognostic score was generated.The prognostic score was calculated based on 3 independent prognostic variables: the Eastern Cooperative Oncology Group (ECOG) scale (0 points if the score was 1, 2 points if it was 2–4), visceral organ involvement (0 points if no involvement, 1 point if involved), and the neutrophil-to-lymphocyte ratio (0 points if ≤3, 1 point if >3). Patients were stratified into good (score 0), intermediate (score 1–2), and poor (score 3–4) prognostic groups based on the risk model. The median survival (95% confidence interval) was 1086 days (500–1617, n = 42), 305 days (237–372, n = 75), and 64 days (44–84, n = 73) for the good, intermediate, and poor prognostic groups, respectively. The c-statistics using the risk model and ECOG scale for the outcome of 1-year mortality were 0.80 and 0.70 (P = 0.038), respectively.In this study, we developed a simple risk model that accurately predicted survival in patients with CUP. This scoring system may be used to help patients and clinicians determine appropriate treatments.     

Sitagliptin After Ischemic Stroke in Type 2 Diabetic Patients: A Nationwide Cohort Study

The cerebrovascular safety and efficacy of sitagliptin, a dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes mellitus (T2DM) with ischemic stroke remains uncertain. The aim of this study was to assess the efficacy and safety of sitagliptin in patients with T2DM with recent ischemic stroke.We analyzed data from the Taiwan National Health Insurance Research Database between March 1, 2009, and December 31, 2011. Ischemic stroke patients were identified from individuals with T2DM. Patients who received sitagliptin were compared with those who did not to evaluate the cardiovascular safety and efficacy of sitagliptin. The primary outcome was a composite of ischemic stroke, myocardial infarction, or cardiovascular death.A total of 5145 type 2 diabetic patients with ischemic stroke met our inclusion criteria and were followed for up to 2.83 years (mean, 1.17 years). Overall, 1715 patients (33.3%) received sitagliptin and 3430 patients (66.7%) did not. The primary composite outcome occurred in 190 patients in the sitagliptin group (11.1%) and in 370 patients in the comparison group (10.8%) (hazard ratio [HR] = 1.02; 95% confidence interval [CI], 0.85–1.21). Patients treated with sitagliptin had a similar risk of ischemic stroke, hemorrhagic stroke, and all-cause mortality with an HR of 0.95 (95% CI, 0.78–1.16, P = 0.612), 1.07 (95% CI, 0.55–2.11, P = 0.834), and 1.00 (95% CI, 0.82–1.22, P = 0.989), respectively, compared with patients not treated with sitagliptin.Treatment with sitagliptin in type 2 diabetic patients with recent ischemic stroke was not associated with increased or decreased risks of adverse cerebrovascular outcomes.     

The potential impact of primary headache disorders on stroke risk

Background

Headache such as migraine is associated with stroke. Studies focused on primary headache disorders (PHDs) as a risk factor for stroke are limited. The purpose of this population-based cohort study was to explore whether patients with PHDs were at a high risk for developing stroke.

Methods

A total of 1346 patients with PHDs were enrolled and compared with 5384 age-, gender- and co-morbidity-matched control cohorts. International Classification of Diseases, Clinical Modification codes were administered for the definition of PHDs, stroke, and stroke risk factors. Cox proportional-hazards regressions were performed for investigating hazard ratios (HR).

Results

PHDs patients exhibited a 1.49 times (95% CI?:1.15–1.98, p < 0.01) higher risk for developing ischaemic stroke compared with that of control cohorts. Both migraine (HR = 1.22, 95% CI?:1.13–1.97, p < 0.05) and tension-type headache (HR = 2.29, 95% CI?:1.22–2.80, p < 0.01) were associated with an increased risk of ischemic stroke. Females with PHDs were at greater risk of developing ischaemic stroke (HR = 1.49, 95% CI?:1.13–1.90, p < 0.01) than those without PHDs. PHDs patient aged 45 to 64 years displayed significantly higher risk to develop ischaemic stroke (HR?=?1.50, 95% CI: 1.11–2.10, p < 0.05) than the matched controls. The impact of PHDs on ischaemic stroke risk became gradually apparent by different following time intervals beyond 2 years after first diagnosis.

Conclusion

PHDs is suggestive of an incremental risk for ischaemic stroke with gender-dependent, age-specific and time-dependent characteristics.

     

Electrocardiographic diagnosis of right ventricular infarction

The electrocardiographic findings in 11 cases of acute right ventricular infarction associated with acute left ventricular inferior wall myocardial infarction are described. The diagnosis of right ventricular infarction was proved by autopsy findings in five cases and supported by hemodynamic data in the other six. Ten of the 11 patients had typical electrocardiographic changes of acute inferior myocardial infarction and one had that of inferior wall injury. Transient S-T segment elevation was present in one (lead V₁) or more of the right precordial leads in eight cases. In the absence of other explanations for the S-T segment elevation, acute right ventricular infarction was most likely the cause. Therefore, when acute inferior myocardial infarction is accompanied by S-T segment elevation in the right precordial leads, the coexistence of right ventricular infarction should be suspected. The sensitivity and specificity of this electrocardiographic sign are yet to be determined.     

The Risk of Erectile Dysfunction in Chronic Obstructive Pulmonary Disease: A Population-Based Cohort Study in Taiwan

The prevalence of erectile dysfunction (ED) in patients with chronic obstructive pulmonary disease (COPD) seemed high; however, large scale of population-based study was absent.We conducted a retrospective cohort study using data from the National Health Insurance system of Taiwan. The cohort included 29,042 male patients who were newly diagnosed with COPD. Patients were recruited between 2000 and 2011, and the date of diagnosis was defined as the index date. Each patient was randomly matched with 1 male person from the general population without COPD according to age and the index year. The occurrence of ED was followed up until the end of 2011. The hazard ratios of ED were estimated using the Cox proportional hazard model after adjusting for age, index year, comorbidities, and medications.The overall incidence of ED was 1.88-fold greater in the COPD cohort than in the non-COPD cohort (24.9 vs 13.3/1000 person-years, 95% confidence interval [CI] = 1.61–2.18). Compared with non-COPD patients, the hazard ratio increased with the number of emergency room visits and admissions for COPD from 1.51 (95% CI 1.29–1.77) to 5.46 (95% CI 3.03–9.84) and from 1.50 (95% CI 1.28–1.76) to 11.5 (95% CI 5.83–22.6), respectively.Patients with COPD are at a significantly higher risk of developing ED compared with the general population regardless of age and presence of comorbidity. The results also support that poor control of COPD status is a key factor affecting ED development.