血管紧张素原基因多态性与肥厚型心肌病的相关性分析

目的 探讨血管紧张素原(AGT)基因的单核苷酸多态性(SNP)位点A943580G与肥厚型心肌病(HCM)的相关性.方法 用PCR-RFLP方法对225个HCM病人和243个正常人的AGT的SNP位点A943580G进行基因分型(此位点与黑色人种中的高血压病人的最大早期充盈速度有关).结果 携带AA和AG基因型的HCM病人的左心室流出道梗阻率明显高于GG基因型的梗阻率(30.1%比17.0%,P＜0.05).通过对发病年龄,性别,室间隔厚度,HCM家族史以及家族猝死史进行调整后,携带A等位基因(AA AG)的HCM病人左心室流出道梗阻率要高于GG基因型病人(OR=2.4,95%CI 1.2 to 4.8).结论 AGT的A等位基因可能是HCM病人发生左心室流出道梗阻的危险因子.     

Association between ACE and AGT polymorphism and cardiovascular risk in acromegalic patients

Purpose

Whether the renin–angiotensin–aldosterone system plays a role or not in the development of cardiovascular morbidity in acromegaly patients is unknown. The aim of the study was to investigate the association between ACE (I/D) and AGT (M235T) gene polymorphisms and cardiovascular and metabolic disorders in the acromegaly.

Methods

The study included one hundred and seventeen acromegalic patients (62 F/55 M, age: 50.2?±?12.3 years) and 106 healthy controls (92 F/14 M, age: 41.4?±?11.3 years). PCR method was used to evaluate the prevalence of ACE and AGT genotype.

Results

The genotypes of ACE polymorphism in acromegalic patients were distributed as follows; 41.0% (n: 48) for DD, 44.4% (n: 52) for ID and 14.5% (n: 17) for II genotype. The control group had significantly different distribution of the ACE polymorphism [48.1% (n: 51) for DD, 25.5% (n: 27) for ID and 26.4% (n: 28) for II genotype]compared to acromegalic group. Regarding AGT polymorphism, AGT-MT genotype was seen in 88.9% of the acromegalic patients while MM and TT genotype (9.4% and 1.7%, respectively) were present in the rest. The controls had similar distribution of the AGT genotype with the acromegaly group (80.2% MT genotype, 15.1% MM genotype and 4.7% TT genotype). Due to the small number of patients with TT allele (n: 2), T carriers for AGT genotype (AGT-MT+TT) were subgrouped and compared to those with AGT-MM group. ACE-DD, ID and II groups had similar anthropometric measures, blood pressure values and baseline GH and IGF-1 levels. Significantly higher baseline GH levels were found in AGT-MM group compared to T allele carriers [40 (16–60) vs. 12 (5–36) µg/L, p?<?0.05]. The compared groups in both polymorphisms had similar fasting plasma glucose levels. Patients with ACE-II genotype had significantly higher HDL-C levels compared to those with ACE-DD and ACE-ID polymorphisms (p?<?0.05) whereas there was no significant difference in lipid profile between AGT-MM group and AGT-T allele carriers. Moreover, the compared groups in both polymorphisms had similar distribution of hyperlipidemia, hypertension, impaired glucose metabolism (prediabetes or type 2 diabetes mellitus) and coronary artery disease. In terms of echocardiographic parameters, systolic and diastolic function was similar among the groups in ACE and AGT genotypes. Interestingly, AGT-MM group had higher mitral inflow A_peak values than T allele carriers (0.94?±?0.46 vs. 0.73?±?0.20; p?=?0.051). No significant difference was observed in LV mass index values in acromegalic patients among the groups in both polymorphisms.

Conclusions

Both ACE (I/D) and AGT (M235T) gene polymorphisms do not seem to have a significant effect on the development of clinical properties or cardiovascular comordities of acromegalic patients.

     

Glucocorticoid Receptor Gene Polymorphisms and Glucocorticoid Resistance in Inflammatory Bowel Disease: A Meta-Analysis

Background

Studies investigating the associations between glucocorticoid receptor gene polymorphisms and glucocorticoid resistance in inflammatory bowel disease report conflicting results.

Aims

We conducted a meta-analysis to assess the possible association between the three most commonly investigated glucocorticoid receptor gene (ER22/23EK, N363S, and BclI) polymorphisms and glucocorticoid resistance in inflammatory bowel disease.

Methods

Articles evaluating the effect of ER22/23EK, N363S, and BclI gene polymorphism on glucocorticoid resistance in inflammatory bowel disease were identified from 1950 to February 2012. After extraction of relevant data, meta-analyses were performed to assess the association between glucocorticoid receptor gene polymorphisms and glucocorticoid resistance in inflammatory bowel disease.

Results

A total of five eligible studies with 942 cases were included. Our analysis showed that ER22/23EK polymorphisms were not associated with glucocorticoid resistance in inflammatory bowel disease [GG versus GA?+?AA: odds ratio (OR)?=?0.58, 95?% confidence interval (CI) 0.16?C2.08]. In N363S polymorphisms, AG?+?GG allele showed no significant effect on glucocorticoid resistance in inflammatory bowel disease compared with AA allele (OR?=?1.19, 95?% CI 0.33?C4.30). In BclI polymorphisms, there was also no association of CG?+?GG allele with glucocorticoid resistance (CC versus CG?+?GG: OR?=?1.22, 95?% CI 0.70?C2.13). For Crohn??s disease (CD) and ulcerative colitis (UC), no statistically significant associations between these three single-nucleotide polymorphisms (SNPs) and glucocorticoid resistance were found. The shape of the funnel plot did not detect publication bias.

Conclusions

The current meta-analysis found no evidence that glucocorticoid receptor gene polymorphisms (ER22/23EK, N363S, and BclI) are associated with glucocorticoid resistance in inflammatory bowel disease treatment. However, this meta-analysis is underpowered for relatively large effect sizes in some SNPs. More well-designed cohort studies should be conducted to fully characterize such an association.     

Selenoprotein S (SEPS1) gene -105G>A promoter polymorphism influences the susceptibility to gastric cancer in the Japanese population

Background

Inflammation is a key factor in the process of carcinogenesis from chronic gastritis induced by Helicobacter pylori. Selenoprotein S (SEPS1) is involved in the control of the inflammatory response in the endoplasmic reticulum (ER). Recently the -105G>A polymorphism in the promoter of SEPS1 was shown to increase pro-inflammatory cytokine expression. We examined the association between this polymorphism and the risk of gastric cancer.

Methods

We took stomach biopsies during endoscopies of 268 Japanese gastric cancer patients (193 males and 75 females, average age 65.3), and 306 control patients (184 males and 122 females, average age 62.7) and extracted the DNA from the biopsy specimens. All subjects provided written informed consent. For the genotyping of the SEPS1 promoter polymorphism at position -105G>A, PCR-RFLP methods were used and the PCR products were digested with PspGI. Logistic-regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI), adjusting for age, sex, and H. pylori infection status.

Results

Among cases, the distribution of genotypes was as follows: 88.4% were GG, 11.2% were GA, and 0.4% were AA. Among controls, the distribution was as follows: 92.5% were GG, 7.2% were GA, and 0.3% were AA. Among males, carrying the A allele was associated with an increased odds of gastric cancer, compared with the GG genotype (OR: 2.0, 95% CI 1.0–4.1, p = 0.07). Compared with the GG genotype, carrying the A allele was significantly associated with increased risks of intestinal type gastric cancer (OR: 2.0, 95%CI 1.0–3.9, p < 0.05) as well as of gastric cancer located in the middle third of the stomach (OR: 2.0, 95%CI 1.0–3.9, p < 0.05).

Conclusion

The -105G>A promoter polymorphism of SEPS1 was associated with the intestinal type of gastric cancer. This polymorphism may influence the inflammatory conditions of gastric mucosa. Larger population-based studies are needed for clarifying the relation between inflammatory responses and SEPS1 polymorphism.     

Clinical characteristics and acute results of catheter ablation for outflow tract ventricular tachycardia or premature beats

Purpose

Contemporary outcome data of catheter ablation for outflow tract tachycardia (OTT) and ventricular premature beats (VPBs) are rare. The aim of this study was to describe the clinical characteristics, the acute procedure success rate, and the long-term survival of patients who underwent an ablation procedure for OTT or VPBs.

Methods

The study was a single-center retrospective cohort study. All 82 consecutive OTT and VPB first ablation procedures between 1999 and 2009 were included. Patients with structural heart disease were excluded.

Results

Mean age was 46?±?13?years. Forty-three percent of the patients were male. All patients were alive after a median follow-up duration of 31?months (interquartile range, 14?C65?months). Eighty-nine percent suffered from palpitations and 12?% had a history of syncope. Ventricular tachycardia was documented in 73?% and monomorphic VPBs in 99?%. Seventy-three percent of the patients were ablated in the right ventricular outflow tract, 15?% in the left ventricular outflow tract, and 12?% in the coronary cusps. Radiofrequency energy was used in 95?% of the patients, cryo energy in 9?%. Acute success was achieved in 78?%. Six patients (7?%) experienced a complication (five pericardial effusions, one pseudo-aneurysm of the femoral artery). Three patients needed pericardiocentesis (4?%).

Conclusion

Ablation for OTT and VPB is successful in the vast majority of cases, with a low but still existing complication rate. Long-term survival was excellent, underscoring the benign nature of this arrhythmia.     

Progression of kidney disease in type 2 diabetes – beyond blood pressure control: an observational study

Background

Essential hypertension is a common, polygenic, complex disorder resulting from interaction of several genes with each other and with environmental factors such as obesity, dietary salt intake, and alcohol consumption. Since the underlying genetic pathways remain elusive, currently most studies focus on the genes coding for proteins that regulate blood pressure as their physiological role makes them prime suspects. The present study examines how polymorphisms of the insertion/deletion (I/D) ACE and M235T AGT genes account for presence and severity of hypertension, and embeds the data in a meta-analysis of relevant studies.

Methods

The I/D polymorphisms of the ACE and M235T polymorphisms of the AGT genes were determined by RFLP (restriction fragment length polymorphism) and restriction analysis in 638 hypertensive patients and 720 normotensive local blood donors in Weisswasser, Germany. Severity of hypertension was estimated by the number of antihypertensive drugs used.

Results

No difference was observed in the allele frequencies and genotype distributions of ACE gene polymorphisms between the two groups, whereas AGT TT homozygotes were more frequent in controls (4.6% vs. 2.7%, P =.08). This became significant (p = 0.035) in women only. AGT TT genotype was associated with a 48% decrease in the risk of having hypertension (odds ratio: 0.52; 95% CI, 0.28 to 0.96), and this risk decreased more significantly in women (odds ratio: 0.28; 95% CI, 0.1 to 0.78). The meta-analysis showed a pooled odds ratio for hypertension of 1.21 (TT vs. MM, 95% CI: 1.11 to 1.32) in Caucasians. No correlation was found between severity of hypertension and a specific genotype.

Conclusion

The ACE I/D polymorphism does not contribute to the presence and severity of essential hypertension, while the AGT M235T TT genotype confers a significantly decreased risk for the development of hypertension in the population studied here. This contrasts to the findings of meta-analyses, whereby the T allele is associated with increased risk for hypertension.     

Substrate metabolism during basal and hyperinsulinemic conditions in adolescents and young-adults with Barth syndrome

Background

Barth syndrome (BTHS) is a rare X-linked disorder that is characterized by mitochondrial abnormalities, infantile or childhood onset of cardioskeletal myopathy, and high mortality rates. It is currently unknown if BTHS related mitochondrial dysfunction results in substrate metabolism abnormalities and thereby contributes to cardioskeletal myopathy in patients with BTHS.

Methods

Adolescents and young adults with BTHS (n?=?5, 20?±?4 yrs) and age and activity matched healthy controls (n?=?5, 18?±?4 yrs) underwent an hyperinsulinemic-euglycemic clamp procedure with stable isotopically labeled tracers for measurement of lipolysis, fatty acid oxidation, glucose disposal, and whole-body proteolysis rates; dual energy x-ray absorptiometry for measurement of body composition and 2-D and strain echocardiography for measurement of left ventricular function.

Results

Participants with BTHS had lower fat-free mass (FFM) (BTHS: 31.4?±?6.9 vs. Control: 46.7?±?5.3 kg, p?<?0.005), lower systolic function (strain, BTHS: -15.2?±?2.4 vs. Control: ?19.0?±?2.4 %, p?<?0.05), greater insulin-stimulated glucose disposal rate per kg FFM (BTHS: 96.5?±?16.3 vs. Control: 67.4?±?17.6 μmol/kgFFM/min, p?<?0.05), lower basal (BTHS: 4.6?±?2.7 vs. Control: 11.9?±?4.4 μmol/kgFM/min, p?<?0.05) and hyperinsulinemic (BTHS: 1.6?±?0.4 vs. Control: 3.6?±?1.6 μmol/kgFM/min, p?<?0.05) lipolytic rate per kg fat mass (FM), and a trend towards higher basal leucine rate of appearance per kg FFM (BTHS: 271.4?±?69.3 vs. Control: 193.1?±?28.7 μmol/kgFFM/hr, p?=?0.07) compared to controls. Higher basal leucine rate of appearance per kg FFM (i.e. whole-body proteolytic rate) tended to be associated with lower left ventricular systolic strain (r?=??0.57, p?=?0.09).

Conclusion

Whole-body fatty acid, glucose and amino acid metabolism kinetics when expressed per unit of body composition are altered and appear to be related to cardioskeletal myopathy in humans with BTHS. Further studies examining myocardial substrate metabolism and whole-body substrate metabolism during increased energy demands (e.g., exercise) and their relationships to skeletal and cardiac function are recommended.     

COPD als wichtiger Risikofaktor in der herzchirurgischen Intensivmedizin

Background

Chronic obstructive pulmonary disease (COPD) is a common comorbidity in patients undergoing cardiac surgery. Our objective was to analyze its prognostic relevance in a cardiac surgery intensive care unit.

Patients and methods

From January 2006 to December 2008, 121?patients with a preoperative history of COPD underwent cardiac surgery and were compared to an age-, sex-, and operation-matched control group without COPD. The primary endpoint was 30-day mortality.

Results

The logistic EuroSCORE was significantly higher in the COPD group (7.8 vs 5.0; p<0.001). There was a higher prevalence of smoking history in the COPD patients (74 vs 36%; p<0.001) and 43% of patients were on beta-agonist treatment preoperatively. Preoperative pulmonary function was significantly impaired and consequently postoperative respiratory failure was more frequent in patients with COPD (9.9 vs 2.5%; p=0.02). Left ventricular function was significantly lower in COPD patients (57 vs 66%; p=0.001). Intensive care stay (p=0.04) and 30-day mortality (5.8 vs 0.8%; p=0.03) were significantly increased in COPD patients.

Conclusion

Patients with COPD and concomitant left ventricular impairment are at high risk for early mortality, postoperative respiratory failure, and prolonged intensive care unit stay.     

Relationship between fragmented QRS complexes and left ventricular systolic and diastolic functions

Background

Fragmented QRS complexes (fQRS) have been associated with increased morbidity and mortality, sudden cardiac death, and recurrent cardiovascular events. The association between left ventricular systolic and diastolic functions and presence of fragmented QRS has not been comprehensively studied to date. We tested the hypothesis that the presence of fragmented QRS is associated with left ventricular systolic and diastolic dysfunction.

Methods

The study included 259 patients who were consecutively admitted to our outpatient clinic for cardiovascular risk factor management. Extensive echocardiographic parameters were obtained from all patients and these were compared with the presence and number of fQRS.

Results

Patients with fQRS were of older age (58?±?12 vs. 55?±?13 years, p?=?0.03) and had prolonged QRS time (105?±?12 vs. 93?±?10 ms, p?<?0.001) and a higher rate of Q waves on ECG (36% vs. 11%, p?<?0.001). In addition, they had worse systolic (lower LVEF%, 44?±?17 vs. 61?±?12, p?<?0.001) and diastolic functions (DT, 177?±?77 vs. 211?±?59 ms, p?<?0.001; IVRT, 81?±?27 vs. 92?±?22 ms, p?=?0.001; E_m, 9?±?4 vs. 10?±?4 cm/s, p?=?0.008; E/E_m ratio, 11?±?5 vs. 8?±?4, p?<?0.001) in comparison to patients with nonfragmented QRS. There was a significant negative correlation between the number of fQRS and left ventricle systolic functions (for LVEF%, r?=???0.595, p?<?0.001). After adjustment for age and gender, the number of fQRS remained significantly negatively associated with left ventricular systolic and diastolic functions.

Conclusion

We found that fQRS is related to left ventricular systolic dysfunction and diastolic dysfunction. fQRS, which may be the result of myocardial ischemia or scar on myocardial electrical parameters at the cellular level, may represent inadequate systolic and diastolic functions.     

Associations between single-nucleotide polymorphisms (+45T>G, +276G>T, ?11377C>G, ?11391G>A) of adiponectin gene and type 2 diabetes mellitus: a systematic review and meta-analysis

Aims/hypothesis

The associations between adiponectin polymorphisms and type 2 diabetes have been studied widely; however, results are inconsistent.

Methods

We searched electronic literature databases and reference lists of relevant articles. A fixed or random effects model was used on the basis of heterogeneity. Sub-group and meta-regression analyses were conducted to explore the sources of heterogeneity.

Results

There were no statistically significant associations between +45T>G (rs2241766), +276G>T (rs1501299), ?11391G>A (rs17300539) and type 2 diabetes risk. However, for ?11377C>G (rs266729), the pooled OR (95% CI) for G vs C allele was 1.07 (1.03?C1.11, p?=?0.001). Subgroup analysis by study design revealed that ?11377C>G (rs266729) dominant model (CG+GG vs CC, p?=?0.0008) and G vs C allele (p?=?0.0004) might be associated with type 2 diabetes risk in population-based case?Ccontrol studies. After stratification by ethnicity, we found that ?11377C>G (rs266729) dominant model (CG+GG vs CC, p?=?0.004) and G vs C allele (p?=?0.001) might be associated with type 2 diabetes risk in white individuals. In individuals with a family history of diabetes, the presence of ?11391G>A (rs17300539) dominant model (GA+AA vs GG) and A vs G allele might be associated with increased risk of type 2 diabetes.

Conclusions/interpretation

The presence of +45T>G (rs2241766), +276G>T (rs1501299) and ?11391G>A (rs17300539) do not appear to influence the development of type 2 diabetes. However, G vs C allele of ?11377C>G (rs266729) might be a risk factor for type 2 diabetes.     

Meta-analysis of functional MBL polymorphisms

Objective

The aim of this study was to determine whether functional mannose-binding lectin gene (MBL) polymorphisms are associated with the susceptibility to rheumatoid arthritis (RA) or primary Sjögren’s syndrome (pSS).

Methods

A meta-analysis was conducted to investigate the potential association of RA or pSS with MBL polymorphisms, including the codon 54 (allele B), codon 57 (allele C), and codon 52 (allele D) variants of exon 1, and the ??550 (allele L) and ??221 (allele X) promoter variants.

Results

A total of 12 comparative studies, including eight RA (1623 patients and 1671 controls) and four pSS (280 patients and 516 controls) studies, were included in the meta-analysis. The meta-analysis revealed no association between the MBL B allele and RA in the overall study population (odds ratio [OR] 0.991, 95?% confidence interval [CI] 0.726–1.355, p?=?0.957). However, the meta-analysis showed significant associations between the MBL D, H, and X alleles and RA in the overall population (OR 1.708, 95?% CI 1.077–2.707, p?=?0.023; OR 1.936, 95?% CI 1.218–3.078, p?=?0.005; OR 1.582, 95?% CI 1.216–2.057, p?=?0.001, respectively). An association was found between the MBL B allele and pSS in the overall study population (OR 0.691, 95?% CI 0.541–0.917, p?=?0.010). Stratification by ethnicity indicated a trend toward an association between the B allele and pSS in European populations, but no association in Asian populations (OR 0.689, 95?% CI 0.465–1.021, p?=?0.063; OR 0.896, 95?% CI 0.311–2.562, p?=?0.838, respectively).

Conclusion

This meta-analysis demonstrated an association between the MBL D, L, and X alleles and the risk of RA. It also demonstrated an association between the MBL B allele and the susceptibility to pSS, suggesting a protective role of the MBL B allele against the development of pSS.     

Improvement in acute contractility and hemodynamics with multipoint pacing via a left ventricular quadripolar pacing lead

Introduction

A quadripolar left ventricular (LV) pacing can deliver multipoint pacing (MPP). It is unknown if this confers improved cardiac function compared to conventional cardiac resynchronization therapy (CRT).

Methods and results

We aimed to characterize changes in acute cardiac contractility and hemodynamics with multisite left ventricular “multipoint” pacing (MPP) in a prospective multicenter study in patients implanted with a CRT-defibrillator incorporating a quadripolar LV lead. The device was programmed to deliver MPP acutely pacing with eight configurations of varying timing delays. Global peak LV radial strain and LV outflow velocity time integral (LVOT VTI) were measured for conventional CRT and each MPP configuration. Out of the eight tested MPP configurations, the one that yielded the best echocardiographic measurement for each patient was defined as “optimal MPP”. Forty CRT recipients had complete radial strain datasets suitable for analysis. Compared to conventional CRT, the mean peak radial strain was significantly higher for the optimal MPP configuration (18.3?±?7.4 vs. 9.3?±?5.3 %, p?<?0.001), and at least one MPP configuration was significantly superior (>20 %) in 63 % of patients. LVOT VTI data were collected in a subset of 13 patients. In these patients, mean VTI was significantly higher for optimal MPP compared to conventional CRT (13.5?±?2.7 vs. 10.9?±?3.3 cm, p?<?0.01).

Conclusion

MPP delivered via a quadripolar LV lead resulted in a significant improvement in acute cardiac contractility and hemodynamics compared to conventional CRT in the majority of patients studied.

Clinical trial registration

Clinicaltrials.gov identifier NCT01044784     

Left atrial wall thickness and outcomes of catheter ablation for atrial fibrillation in patients with hypertrophic cardiomyopathy

Purpose

Catheter ablation of atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM) is still challenging, and it is unclear whether the difficulty is caused by the hypertrophy of left atrial (LA) myocardial wall thickness. The objective of the study was to compare the LA wall thickness and AF ablation outcomes between patients with HCM and those without structural heart disease.

Methods

The present study enrolled 17 consecutive HCM patients (63?±?12 years) with drug-refractory AF and 34 control patients without any detectable heart disease, whose age, gender, type of AF, and LA dimension were matched to the HCM patients. The myocardial wall thickness of 11 distinct LA locations, measured using 64-slice computed tomography images, and AF ablation outcomes were compared between the two groups.

Results

The LA wall thickness did not differ at 9 of the 11 locations and was significantly thinner in the HCM patients than in the control patients at the mid-posterior wall (1.44?±?0.17 vs. 1.58?±?0.22, p?=?0.04) and infero-posterior wall (1.62?±?0.16 vs. 1.74?±?0.18, p?=?0.03). Although antiarrhythmic drugs were used more frequently in the HCM patients (p?=?0.008), the rate of maintaining sinus rhythm during the follow-up did not differ between the HCM and control patients (53 vs. 56 % after the initial ablation [log-rank p?=?0.78] and 82 and 88 % after the repeat procedure [log-rank p?=?0.35]).

Conclusions

The LA wall in the HCM patients with AF was not thicker than that of the matched patients without structural heart disease. Catheter ablation of AF showed favorable outcomes in both patient groups.     

Effects of allopurinol on cardiac function and oxidant stress in chronic intermittent hypoxia

Rationale

Obstructive sleep apnea is associated with left ventricular (LV) dysfunction, oxidant stress, and chronic intermittent hypoxia (CIH). Allopurinol (ALLO) is a xanthine oxidase inhibitor that also scavenges free radicals.

Objectives

Using an animal model of CIH we hypothesized that ALLO decreases oxidant stress and cardiac injury.

Materials and methods

Rats were exposed to either CIH (nadir 4–6%, approximately once per minute) or room air (handled controls, HC) for 8 h a day for 10 days. Four treatment groups (six to ten animals per group) were studied: CIH/ALLO, CIH/placebo (PLAC), HC/ALLO, and HC/PLAC. Outcomes included myocardial lipid peroxides (LPO) for oxidant stress, fraction shortening of the LV cavity for cardiac function (LVFS) and an assay for myocyte apoptosis.

Results

LPO was lower in CIH/ALLO group compared to CIH/PLAC (179?±?102 vs. 589?±?68 mcg/mg protein, p?<?0.05). LVFS was greater in ALLO animals than PLAC in both CIH and HC (CIH/ALLO 48.6?±?2.3% vs. CIH/PLAC 38?±?1.4%; HC/ALLO 64.9?±?1.8% vs. HC/PLAC 51.5?±?1.5%; both p?<?0.05). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay showed fewer apoptotic nuclei in LV myocardium in CIH/ALLO compared to CIH/PLAC (38.0?±?1.4 vs. 48.6?±?2.3 positive nuclei per 2.5 mm² area, p?<?0.05).

Conclusion

ALLO is associated with improvement in CIH-associated oxidant stress, myocardial dysfunction, and apoptosis in rats.     

Radial artery graft vs. saphenous vein graft for coronary artery bypass surgery

Objectives

Coronary artery bypass grafting (CABG) is the best therapeutic option for multivessel coronary artery diseases. The internal thoracic artery is usually used for the left anterior descending coronary artery. However, it is still not clear what the best conduit is for non-left anterior descending coronary arteries. This research sought to assess the efficacy of the radial artery versus the saphenous vein in this context.

Methods

A systematic literature search was performed for randomized clinical trials (RCT) published in MEDLINE, EMBASE, and the Cochrane Library. RCTs reporting angiographic comparisons and clinical events of the radial artery versus the saphenous vein were included.

Results

Six trials (1,860 participants, 1,188 radial artery grafts, 1,178 saphenous vein grafts) were included in this review. The radial artery was associated with a significantly lower incidence of graft failure (p?<?0.05) and of repeat coronary operation (p?<?0.05). There was no significant trend toward decreased cardiac death and myocardial infarction with the use of a radial artery (p?>?0.05; p?>?0.05). As determined by the GRADE method, the evidence quality was low for repeat operation and very low for other variables.

Conclusion

The radial artery can be weakly recommended as a selective conduit but cannot always be considered better than the saphenous vein.     

Novel electrocardiographic features in carriers of hypertrophic cardiomyopathy causing sarcomeric mutations

Objectives

The sensitivity and specificity of the conventional 12-lead ECG to identify carriers of hypertrophic cardiomyopathy (HCM) – causing mutations without left ventricular hypertrophy (LVH) has been limited. We assessed the ability of novel electrocardiographic parameters to improve the detection of HCM mutation carriers.

The effects of atrial ganglionated plexi stimulation on ventricular electrophysiology in a normal canine heart

Aims

Atrial ganglionated plexi (GP) have been shown to modulate atrial electrophysiology and play an important role in atrial fibrillation initiation and maintenance. The purpose of this study was to investigate the effects of atrial GP stimulation (GPS) on ventricular refractoriness, restitution properties and electrical alternans.

Methods

In 12 anesthetized dogs, two multiple electrode catheters were sutured at left and right ventricular free walls for recording. Monophasic action potentials were recorded from six epicardial ventricular sites. Ventricular effective refractory period (ERP), action potential duration (APD) restitution properties and APD alternans were measured at baseline and during GPS.

Results

Compared with baseline, GPS significantly prolonged ventricular ERP and APD at all sites and decreased their spatial dispersions (P?<?0.05 for all). GPS also significantly flattened ventricular restitution curves and decreased the maximal slope of restitution curves at each site (P?<?0.05 for all). APD alternans occurred at shorter pacing cycle length at each site during GPS when compared with baseline (P?<?0.05 for all).

Conclusions

GPS prolonged ventricular ERP, decreased the slope of restitution curves and delayed APD alternans, indicating that GPS may exert a protective role for ventricular arrhythmias.     

Interleukin-10 Promoter 1082/−819/−592 Polymorphisms are Associated with Asthma Susceptibility in Asians and Atopic Asthma: A Meta-Analysis

Background

Although interleukin-10 (IL-10) is a potent inhibitor of allergic diseases, the association between promoter ?1082/?819/?592 polymorphisms and asthma susceptibility remains inconclusive. We sought to determine if IL-10 promoter ?1082/?819/?592 polymorphisms contribute to asthma susceptibility and are associated with phenotypes of atopic asthma.

Methods

Systematic computerized searches were performed. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated by using random-effect and fixed-effect models, based on between-study heterogeneity. Subgroup analyses were performed according to age, ethnicity, and atopy. Publication bias was detected by funnel plot using Egger’s test.

Results

A total of 4,716 asthmatic patients and 5,093 controls were included. The asthma susceptibility correlated significantly with IL-10 promoter gene ?1082 polymorphism [OR (95 % CI) 1.26 (1.02, 1.55) for AA vs. AG + GG] and ?592 polymorphism [OR (95 % CI) 1.12 (1.07, 1.34) for AC + AA vs. CC] (both P < 0.05), but not with ?819 polymorphism (P > 0.05). Subgroup analyzes suggested that the AA versus AG + GG genotype of ?1082A/G polymorphism and AC + AA versus CC genotype of ?592A/C polymorphism contributed significantly to increased asthma susceptibility in adults [OR (95 % CI) 1.39 (1.03, 1.87) for ?1082A/G and 1.53 (1.25, 1.87) for ?592A/C polymorphism]. The Asian population [OR (95 % CI) 1.35 (1.1, 1.7) for ?1082A/G and 1.4 (1.12, 1.64) for ?592A/C polymorphism] and subjects with atopic asthma [OR (95 % CI) 1.49 (1.18, 1.88) for ?1082A/G and 1.23 (1.01, 1.48) for ?592A/C polymorphism] also had an increased susceptibility of asthma. No publication bias was detected.

Conclusions

IL-10 promoter ?1028A/G, ?592A/C polymorphisms and their haplotypes, but not ?819T/C polymorphism, correlate with asthma susceptibility.     

Experiencing the Culture of Academic Medicine: Gender Matters, A National Study

BACKGROUND

Energized and productive faculty are critical to academic medicine, yet studies indicate a lack of advancement and senior roles for women.

OBJECTIVE

Using measures of key aspects of the culture of academic medicine, this study sought to identify similarity and dissimilarity between perceptions of the culture by male and female faculty.

DESIGN

The C - Change Faculty Survey was used to collect data on perceptions of organizational culture.

PARTICIPANTS

A stratified random sample of 4,578 full-time faculty at 26 nationally representative US medical colleges (response rate 52 %). 1,271 (53 %) of respondents were female.

MAIN MEASURES

Factor analysis assisted in the creation of scales assessing dimensions of the culture, which served as the key outcomes. Regression analysis identified gender differences while controlling for other demographic characteristics.

KEY RESULTS

Compared with men, female faculty reported a lower sense of belonging and relationships within the workplace (T?=??3.30, p?<?0.01). Self-efficacy for career advancement was lower in women (T?=??4.73, p?<?0.001). Women perceived lower gender equity (T?=??19.82, p?<?0.001), and were less likely to believe their institutions were making changes to address diversity goals (T?=??9.70, p?<?0.001). Women were less likely than men to perceive their institution as family-friendly (T?=??4.06, p?<?0.001), and women reported less congruence between their own values and those of their institutions (T?=??2.06, p?<?0.05). Women and men did not differ significantly on levels of engagement, leadership aspirations, feelings of ethical/moral distress, perception of institutional commitment to faculty advancement, or perception of institutional change efforts to improve support for faculty.

CONCLUSIONS

Faculty men and women are equally engaged in their work and share similar leadership aspirations. However, medical schools have failed to create and sustain an environment where women feel fully accepted and supported to succeed; how can we ensure that medical schools are fully using the talent pool of a third of its faculty?     

Germline mutations of aryl hydrocarbon receptor-interacting protein (<Emphasis Type="Italic">AIP</Emphasis>) gene and somatostatin receptor 1–5 and <Emphasis Type="Italic">AIP</Emphasis> immunostaining in patients with sporadic acromegaly with poor versus good response to somatostatin analogues

Objective

To determine aryl hydrocarbon interacting protein (AIP) gene variations and AIP and somatostatin receptor (SSTR) 1–5 immunostaining in patients with apparently sporadic acromegaly with poor versus good response to somatostatin analogues (SRLs).

Methods

A total of 94 patients (66 with poor and 28 with good response to SRLs) were screened for the AIP gene variations using Sanger sequencing. Immunostaining was performed in 60 tumors.

Results

Several variations, albeit some with undetermined significance, were detected, especially in poor responder patients. The prevalence of AIP mutation was 2.1% in the whole group and 1.5% in patients with poor response to SRLs. AIP, SSTR2A, and SSTR2B immunostainings were decreased in patients with poor response (p?<?0.05 for all), and other SSTRs did not differ between the groups (p?>?0.05 for all). Patients with low AIP had decreased levels of SSTR2A and SSTR3 (p?<?0.05 for all). AIP and SSTR2A immunostainings were positively correlated to the treatment response and age at diagnosis was negatively correlated (p?<?0.05 for all). In poor responder patients with high SSTR2A immunostaining, SSTR2B immunostaining and preoperative tumor size were positively and negatively correlated, respectively, to SRL response (p?<?0.05 for all).

Conclusions

Lack of response to SRLs does not necessarily increase the risk of harboring AIP mutations. The finding of decreased AIP, SSTR2A, and SSTR2B immunostaining in patients with poor response to SRLs and decreased SSTR2A and SSTR3 level in those with low AIP immunostaining suggests a possible interaction between AIP and some SSTR subtypes that might alter SRL sensitivity.