Degree of Contracture Related to Residual Muscle Shoulder Strength in Children with Obstetric Brachial Plexus Lesions

Background and Objectives

 Little is known about the relation between residual muscle strength and joint contracture formation in neuromuscular disorders. This study aimed to investigate the relation between residual muscle strength and shoulder joint contractures in children with sequelae of obstetric brachial plexus lesion (OBPL). In OBPL a shoulder joint contracture is a frequent finding. We hypothesize that residual internal and external rotator strength and their balance are related to the extent of shoulder joint contracture.

Methods

 Clinical assessment was performed in 34 children (mean 10.0 years) with unilateral OBPL and Narakas classes I–III. External and internal rotation strengths were measured with the shoulder in neutral position using a handheld dynamometer. Strength on the affected side was given as percentage of the normal side. Contracture was assessed by passive internal and external rotations in degrees (in 0° abduction). Mallet classification was used for active shoulder function.

Results

 External and internal rotation strengths on the affected side were approximately 50% of the normal side and on average both equally affected: 56% (SD 18%) respectively 51% (SD 27%); r = 0.600, p = 0.000. Residual strengths were not related to passive internal or external rotation (p > 0.200). Internal rotation strength (r =  − 0.425, p <0.05) was related to Narakas class. Mallet score was related to external and internal rotation strengths (r = 0.451 and r = 0.515, respectively; p < 0.01).

Conclusion

 The intuitive notion that imbalances in residual muscle strength influence contracture formation cannot be confirmed in this study. Our results are of interest for the understanding of contracture formation in OBPL.     

Influence of weather and atmospheric pollution on physical activity in patients with COPD

Rationale

Information concerning how climate and atmospheric pollutants affects physical activity in COPD patients is lacking and might be valuable in determining when physical activity should be encouraged.

Methods

Seventy-three stable COPD patients recorded on daily diary cards worsening of respiratory symptoms, peak expiratory flow rate, hours spent outside the home and the number of steps taken per day. Pedometry data was recorded on 16,478 days, an average of 267 days per patient (range 29-658). Daily data for atmospheric PM₁₀ and ozone (O₃) were obtained for Bloomsbury Square, Central London from the Air Quality Information Archive databases. Daily weather data were obtained for London Heathrow from the British Atmospheric Data Archive.

Results

Colder weather below 22.5 °C, reduced daily step count by 43.3 steps day per°C (95 % CI 2.14 to 84.4; p = 0.039) and activity was lower on rainy than dry days (p = 0.002) and on overcast compared to sunny days (p < 0.001). Daily step count was 434 steps per day lower on Sunday than Saturday (p < 0.001) and 353 steps per day lower on Saturday than Friday (p < 0.001). After allowance for these effects, higher O₃ levels decreased activity during the whole week (-8 steps/ug/m3; p = 0.005) and at weekends (-7.8 steps/ug/m3; p = 0.032). Whilst, during the week PM₁₀ reduced activity (p = 0.018) but not during the weekend.

Conclusions

Inactivity of COPD patients is greatest on cold, wet and overcast days and at the weekends. This study also provides evidence of an independent effect of atmospheric pollution at high levels.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-015-0229-z) contains supplementary material, which is available to authorized users.     

Beh?et’s disease in HLA-B*51 negative Germans and Turks shows association with HLA-Bw4-80I

Introduction

Behçet’s disease (BD) as systemic vasculitis of unknown etiology is associated with HLA-B*51 in European and Asian populations. HLA-A*26 was claimed as an additional BD susceptibility marker in Japanese and Greek patients. This study was performed to test for HLA associations in HLA-B*51 negative German and Turkish BD populations.

Methods

In total, 65 German and 46 Turkish patients lacking HLA-B*51 were analyzed in comparison to healthy HLA-B*51 negative Germans (n = 1500) and Turks (n = 130). HLA-A/B genotypes were determined by SSOP. P-values with correction for multiple testing (p_c), χ2-test and odds ratio (OR) were used for statistical evaluation.

Results

HLA-A*26 was significantly more frequent in HLA-B*51⁻ German patients [p_c = 0.0076, OR = 3.23, 95% CI 1.63 to 6.39] than in respective controls. HLA-A*26 was also elevated in a smaller group of Turkish patients versus the controls. Significant association of HLA-Bw4 with isoleucine at amino-acid position 80 (HLA-Bw4-80I) was found in the HLA-B*51⁻ German cohort of BD patients [p_c = 0.0042, OR = 2.35, 95% CI 1.41 to 3.93) and in the Turkish patients in comparison to the respective controls [p = 0.025, OR = 2.17, 95% CI 1.09 to 4.31]. On the contrary, HLA-Bw4-80 T was reduced in both HLA-B*51⁻ BD patient cohorts.

Conclusions

The study shows a significant association of HLA-Bw4-80I present on HLA-B*51 as well as on other B-locus molecules with BD. This indicates that distinctive Bw4 epitopes on HLA-B locus molecules could play a role in BD pathogenesis. The study also indicates an association with HLA-A*26 in German and Turkish BD patients as a genetic risk factor independent of HLA-B*51.     

Associations between Vascular Health Indices and Serum Total,Free and Bioavailable 25-Hydroxyvitamin D in Adolescents

Objective

The role of vitamin D in cardiovascular health remains debated as results have been inconsistent. Previous studies have not considered the bioavailability of 25-hydroxy vitamin D [25(OH)D]. Objectives of our study were to investigate the association between serum concentrations of total, free and bioavailable 25(OH)D and independent predictors of cardiovascular risk such as flow mediated dilatation (FMD) and augmentation index (AIx).

Design

This cross-sectional study included 47 post-menarchal, adolescent females [31 African American (AA) and 16 European American (EA)].

Methods

AIx was standardized to a heart rate of 75 beats/min (AIx75). Free and bioavailable 25(OH)D concentrations were calculated from standard formulas.

Results and Conclusions

Mean age of the participants was 15.8±1.4 years and mean body mass index was 23.1±4.0 kg/m². Serum total 25(OH)D was not associated with FMD, but was positively associated with AIx75 in the adjusted model (rho = 0.4, P = 0.03). AIx75 was positively associated with bioavailable 25(OH)D (rho = 0.4, P = 0.004) and free 25(OH)D (rho = 0.4, P = 0.009) and the associations persisted after adjusting for covariates. In race-specific analyses, total, free and bioavailable 25(OH)D were strongly positively associated with AIx75 in AA (rho = 0.5, 0.4, 0.4, respectively), which persisted even after adjusting for covariates. Whereas in EA there was an inverse association between total 25(OH)D and AIx75 in EA (rho = −0.6), which attenuated after adjusting for covariates.

Conclusion

Circulating total, free and bioavailable 25(OH)D were associated with arterial stiffness in adolescent girls, and these associations were race dependent. Notwithstanding, the implications of associations between vascular function indices and 25(OH)D remains unclear.     

The ZC3HC1 rs11556924 polymorphism is associated with increased carotid intima-media thickness in patients with rheumatoid arthritis

Introduction

Rheumatoid arthritis (RA) is a complex polygenic disease associated with chronic inflammation, accelerated atherosclerosis and increased cardiovascular (CV) mortality. A recent meta-analysis has described the ZC3HC1 rs11556924 polymorphism as one of the most important signals associated with coronary artery disease (CAD) in non-rheumatic Caucasian individuals. In this study we evaluated the potential association of this gene polymorphism with subclinical atherosclerosis assessed by the evaluation of carotid intima-media thickness (cIMT) in RA patients.

Methods

This study included 502 RA patients from Northern Spain. The ZC3HC1 rs11556924 polymorphism was genotyped with TaqMan single-nucleotide polymorphism (SNP) genotyping assays (C__31283062_10) in a 7900HT real-time polymerase chain reaction (PCR) system. cIMT was also assessed in these patients by carotid ultrasonography (US) technology.

Results

RA patients carrying the TT genotype had significantly higher cIMT values than those homozygous for the CC genotype (mean ± standard deviation (SD): 0.76 ± 0.18 mm and mean ± SD: 0.71 ± 0.16 mm respectively; P = 0.03) even after adjusting the results for sex, age at the time of US study, follow-up time and traditional CV risk factors (P = 0.04) evidencing that the effect conferred by ZC3HC1 rs11556924 polymorphism is independent of the traditional CV risk factors.

Conclusion

Our results indicate that ZC3HC1 rs11556924 polymorphism is associated with subclinical atherosclerosis in RA.     

Interferon regulatory factor 5 genetic variants are associated with cardiovascular disease in patients with rheumatoid arthritis

Introduction

Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis and increased cardiovascular (CV) disease risk. Interferon regulatory factor 5 (IRF5) is a regulator of type I interferon induction. Recently, researchers have described an association between multiple single-nucleotide polymorphisms of the IRF5 gene and some rheumatic disorders. In this study, we aimed to evaluate whether three different haplotype blocks within the IRF5 locus which have been shown to alter the protein function are involved in the risk of CV events occurring in Spanish RA patients.

Methods

Three IRF5 polymorphisms (rs2004640, rs2070197 and rs10954213) representative of each haplotype group were genotyped by performing TaqMan assays using a 7900HT Fast Real-Time PCR System with tissue from a total of 2,137 Spanish patients diagnosed with RA. Among them, 390 (18.2%) had experienced CV events. The relationship of IRF5 genotypes and haplotypes to CV events was tested using Cox regression.

Results

Male sex, age at RA diagnosis and most traditional risk factors (hypertension, dyslipidemia and smoking habit) were associated with increased risk for CV events in the RA population. Interestingly, a protective effect of both IRF5 rs2004640 GG and IRF5 rs10954213 GG genotypes against the risk for CV events after adjusting the results for sex, age at RA diagnosis and traditional CV disease risk factors was observed (hazard ratio (HR) = 0.6, 95% confidence interval (CI) = 0.38 to 0.92, P = 0.02; and HR = 0.58, 95% CI = 0.36 to 0.95, P = 0.03, respectively). Moreover, we detected a protective effect of the GTG haplotype against the risk for CV events after adjusting the results for potential confounding factors (HR = 0.72, 95% CI = 0.56 to 0.93, P = 0.012).

Conclusions

Our results reveal that IRF5 gene variants are associated with risk of CV events in patients with RA.     

Decrease in quality of life predicts mortality in adult patients with pulmonary arterial hypertension due to congenital heart disease

Background

Decrease in quality of life (QoL) in left-sided heart failure precedes poor survival, which can be reversed with exercise training. We investigated whether QoL is associated with mortality in pulmonary arterial hypertension due to congenital heart disease (PAH-CHD) patients.

Methods

In this observational study, PAH-CHD adults referred for PAH-specific therapy were included. QoL surveys (SF36) were recorded during 2 years of therapy. Based on shift in SF36 scores during this period, patients had either decreased or non-decreased QoL. Subsequently, the patients were followed for mortality.

Results

Thirty-nine PAH-CHD patients (mean age 42, 44 % male, 49 % Down’s syndrome) were analysed. Following PAH-specific therapy, SF36 physical component summary (PCS) decreased in 13 (35–31 points, p = 0.001) and showed no decrease in 26 patients (34–43 points, mean values, p < 0.001). Post-initiation phase, median follow-up was 4.5 years, during which 12 deaths occurred (31 %), 10 (56 %) in the decreased and 2 (10 %) in the non-decreased group (p = 0.002). Cox regression showed a decrease in SF36 PCS predicted mortality (HR 3.4, 95 % CI 1.03–11, p = 0.045).

Conclusions

In PAH-CHD patients, decrease in SF36 PCS following initiation of PAH-specific therapy is a determinant of mortality.

Electronic supplementary material

The online version of this article (doi:10.1007/s12471-015-0666-9) contains supplementary material, which is available to authorized users.     

Remote magnetic navigation vs. manual navigation for ablation of ventricular tachycardia: a meta-analysis

Background

The purpose of this study was to prospectively evaluate the efficacy and safety of remote magnetic navigation (RMN) in comparison with manual catheter navigation (MCN) in performing ventricular tachycardia ablation.

Methods

An electronic search was performed using PubMed (1948–2013) and EMBASE (1974–2013) studies comparing RMN with MCN which were published prior to 31 December 2013. Outcomes of interest were as follows: acute success, recurrence rate, complications, total procedure and fluoroscopic times. Standard mean difference (SMD) and its 95 % confidence interval (CI) were used for continuous outcomes; odds ratios (OR) were reported for dichotomous variables.

Results

Four non-randomised studies, including a total of 328 patients, were identified. RMN was deployed in 191 patients. Acute success and long-term freedom from arrhythmias were not significantly different between the RMN and control groups (OR 1.845, 95 % CI 0.731–4.659, p = 0.195 and OR 0.676, 95 % CI 0.383–1.194, p = 0.177, respectively). RMN was associated with less peri-procedural complications (OR 0.279, 95 % CI 0.092–0.843, p = 0.024). Shorter procedural and fluoroscopy times were achieved (95 % CI -0.487 to -0.035, p = 0.024 and 95 % CI -1.467 to -0.984, p<0.001, respectively).

Conclusion

The acute and long-term success rates for VT ablation are equal between RMN and MCN, whereas the RMN-guided procedure can be performed with a lower complication rate and less procedural and fluoroscopic times. More prospective randomised trials will be needed to better evaluate the superior role of RMN for catheter ablation of ventricular tachycardia.     

CMR-derived TAPSE measurement: a semi-quantitative method of right ventricular function assessment in patients with hypertrophic cardiomyopathy

Aim

To compare cardiovascular magnetic resonance (CMR)-derived right ventricular fractional shortening (RVFS), tricuspid annular plane systolic excursion with a reference point within the right ventricular apex (TAPSE_in) and with one outside the ventricle (TAPSE_out) with the standard volumetric approach in patients with hypertrophic cardiomyopathy (HCM).

Methods and results

105 patients with HCM and 20 healthy subjects underwent CMR. In patients with HCM, TAPSE_in (r = 0.31, p = 0.001) and RVFS (r = 0.35, p = 0.0002) revealed a significant but weak correlation with right ventricular ejection fraction (RVEF), whereas TAPSE_out (r = 0.57, p < 0.0001) showed a moderate correlation with RVEF. The ability to predict RVEF < 45 % in HCM patients was best for TAPSE_out. In patients with hypertrophic obstructive cardiomyopathy (HOCM), RVEF showed a significant but weak correlation with TAPSE_out (r = 0.36, p = 0.02) and no correlation with TAPSE_in (r = 0.05, p = 0.07) and RVFS (r = 0.02, p = 0.2). In patients with hypertrophic non-obstructive cardiomyopathy (HNCM), there was a moderate correlation between RVEF and TAPSE_out (r = 0.57, p < 0.0001) and a weak correlation with TAPSE_in (r = 0.39, p = 0.001) and RVFS (r = 0.38, p = 0.002). In the 20 healthy controls, there was a strong correlation between RVEF and all semi-quantitative measurements.

Conclusion

CMR-derived TAPSE_in is not suitable to determine right ventricular function in HCM patients. TAPSE_out showed a good correlation with RVEF in HNCM patients but only a weak correlation in HOCM patients. TAPSE_out might be used for screening but the detection of subtle changes in RV function requires the 3D volumetric approach.     

Identification of a common risk haplotype for canine idiopathic epilepsy in the ADAM23 gene

Background

Idiopathic epilepsy is a common neurological disease in human and domestic dogs but relatively few risk genes have been identified to date. The seizure characteristics, including focal and generalised seizures, are similar between the two species, with gene discovery facilitated by the reduced genetic heterogeneity of purebred dogs. We have recently identified a risk locus for idiopathic epilepsy in the Belgian Shepherd breed on a 4.4 megabase region on CFA37.

Results

We have expanded a previous study replicating the association with a combined analysis of 157 cases and 179 controls in three additional breeds: Schipperke, Finnish Spitz and Beagle (p_c = 2.9e–07, p_GWAS = 1.74E-02). A targeted resequencing of the 4.4 megabase region in twelve Belgian Shepherd cases and twelve controls with opposite haplotypes identified 37 case-specific variants within the ADAM23 gene. Twenty-seven variants were validated in 285 cases and 355 controls from four breeds, resulting in a strong replication of the ADAM23 locus (p_raw = 2.76e–15) and the identification of a common 28 kb-risk haplotype in all four breeds. Risk haplotype was present in frequencies of 0.49–0.7 in the breeds, suggesting that ADAM23 is a low penetrance risk gene for canine epilepsy.

Conclusions

These results implicate ADAM23 in common canine idiopathic epilepsy, although the causative variant remains yet to be identified. ADAM23 plays a role in synaptic transmission and interacts with known epilepsy genes, LGI1 and LGI2, and should be considered as a candidate gene for human epilepsies.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1651-9) contains supplementary material, which is available to authorized users.     

Right ventricular function in dilated cardiomyopathy and ischemic heart disease: assessment with non-invasive imaging

Background

Dilated cardiomyopathy and ischaemic heart disease can both lead to right ventricular (RV) dysfunction. Direct comparisons of the two entities regarding RV size and function using state-of-the-art imaging techniques have not yet been performed. We aimed to determine RV function and volume in dilated cardiomyopathy and ischaemic heart disease in relation to left ventricular (LV) systolic and diastolic function and systolic pulmonary artery pressure.

Methods and results

A well-characterised group (cardiac magnetic resonance imaging, echocardiography, coronary angiography and endomyocardial biopsy) of 46 patients with dilated cardiomyopathy was compared with LV ejection fraction (EF)-matched patients (n = 23) with ischaemic heart disease. Volumes and EF were determined with magnetic resonance imaging, diastolic LV function and pulmonary artery pressure with echocardiography.After multivariable linear regression, four factors independently influenced RVEF (R² = 0.51, p < 0.001): LVEF (r = 0.54, p < 0.001), ratio of peak early and peak atrial transmitral Doppler flow velocity as measure of LV filling pressure (r = − 0.52, p < 0.001) and tricuspid regurgitation flow velocity as measure of pulmonary artery pressure (r = − 0.38, p = 0.001). RVEF was significantly worse in patients with dilated cardiomyopathy compared with ischaemic heart disease: median 48 % (interquartile range (IQR) 37–55 %) versus 56 % (IQR 48–63 %), p < 0.05.

Conclusions

In patients with dilated cardiomyopathy and ischaemic heart disease, RV function is determined by LV systolic and diastolic function, the underlying cause of LV dysfunction, and pulmonary artery pressure. It was demonstrated that RV function is more impaired in dilated cardiomyopathy.     

Smoking cessation after an acute coronary syndrome: immediate quitters are successful quitters

Background

Cardiovascular disease (CVD) prevention guidelines stress the importance of smoking cessation and recommend intensive follow-up. To guide the development of such cessation support strategies, we analysed the characteristics that are associated with successful smoking cessation after an acute coronary syndrome (ACS).

Methods

We used data from the Randomised Evaluation of Secondary Prevention for ACS patients coordinated by Outpatient Nurse SpEcialists (RESPONSE) trial (n = 754). This was designed to quantify the impact of a nurse-coordinated prevention program, focusing on healthy lifestyles, traditional CVD risk factors and medication adherence. For the current analysis we included all smokers (324/754, 43 %). Successful quitters were defined as those who reported abstinence at 1 year of follow-up.

Results

The majority of successful quitters quit immediately after the ACS event and remained abstinent through 1 year of follow-up, without extra support (128/156, 82 %). Higher education level (33 vs. 15 %, p < 0.01), no history of CVD (87 vs. 74 %, p < 0.01) and being on target for LDL-cholesterol level at 1 year (78 vs. 63 %, p < 0.01) were associated with successful quitting.

Conclusion

The majority of successful quitters at 1 year stopped immediately after their ACS. Patients in this group showed that it was within their own ability to quit, and they did not relapse through 1 year of follow-up. Our study indicates that in a large group of patients who quit immediately after a life-threatening event, no relapse prevention program is needed.     

The ethnicity-specific association of biomarkers with the angiographic severity of coronary artery disease

Background

Risk factor burden and clinical characteristics of patients with coronary artery disease (CAD) differ among ethnic groups. We related biomarkers to CAD severity in Caucasians, Chinese, Indians and Malays.

Methods

In the Dutch-Singaporean UNICORN coronary angiography cohort (n = 2033) we compared levels of five cardiovascular biomarkers: N-terminal pro-brain natriuretic peptide (NTproBNP), high-sensitivity C-reactive protein (hsCRP), cystatin C (CysC), myeloperoxidase (MPO) and high-sensitivity troponin I (hsTnI). We assessed ethnicity-specific associations of biomarkers with CAD severity, quantified by the SYNTAX score.

Results

Adjusted for baseline differences, NTproBNP levels were significantly higher in Malays than in Chinese and Caucasians (72.1 vs. 34.4 and 41.1 pmol/l, p < 0.001 and p = 0.005, respectively). MPO levels were higher in Caucasians than in Indians (32.8 vs. 27.2 ng/ml, p = 0.026), hsTnI levels were higher in Malays than in Caucasians and Indians (33.3 vs. 16.4 and 17.8 ng/l, p < 0.001 and p = 0.029) and hsTnI levels were higher in Chinese than in Caucasians (23.3 vs. 16.4, p = 0.031). We found modifying effects of ethnicity on the association of biomarkers with SYNTAX score. NTproBNP associated more strongly with the SYNTAX score in Malays than Caucasians (β 0.132 vs. β 0.020 per 100 pmol/l increase in NTproBNP, p = 0.032). For MPO levels the association was stronger in Malays than Caucasians (β 1.146 vs. β 0.016 per 10 ng/ml increase, p = 0.017). Differing biomarker cut-off levels were found for the ethnic groups.

Conclusion

When corrected for possible confounders we observe ethnicity-specific differences in biomarker levels. Moreover, biomarkers associated differently with CAD severity, suggesting that ethnicity-specific cut-off values should be considered.     

Comparison of cancer incidence among patients with rheumatic disease: a retrospective cohort study

Introduction

Rheumatic diseases (RDs) are associated with different cancers; however, it is unclear whether particular cancers are more prevalent in certain RDs. In the present study, we examined the relative incidence of several cancers in a single homogeneous cohort of patients with different RDs.

Methods

Patients (N = 3,586) diagnosed with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermatomyositis (DM) or polymyositis were included. Cancer diagnosis was based on histopathology. The 2008 Korean National Cancer Registry served as the reference for calculating standardized incidence ratios (SIRs).

Results

During the follow-up period of 31,064 person-years, 187 patients developed cancer. RA and SLE patients showed an increased risk of non-Hodgkin’s lymphoma (SIR for RA patients = 3.387, 95% confidence interval (CI) = 1.462 to 6.673; SIR for SLE patients = 7.408, 95% CI = 2.405 to 17.287). SLE patients also had a higher risk of cervical cancer (SIR = 4.282, 95% CI = 1.722 to 8.824). SSc patients showed a higher risk of lung cancer (SIR = 4.917, 95% CI = 1.977 to 10.131). Endometrial cancer was increased only in patients with DM (SIR = 30.529, 95% CI = 3.697 to 110.283). RA patients had a lower risk for gastric cancer (SIR = 0.663, 95% CI = 0.327 to 0.998). The mean time between the RD and cancer diagnoses ranged from 0.1 to 16.6 years, with the shortest time observed in patients with DM (2.0 ± 2.1 years).

Conclusions

Different RDs are associated with particular cancers. Thus, cancer surveillance tailored to specific RDs might be beneficial.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-014-0428-x) contains supplementary material, which is available to authorized users.     

Morphological and functional carotid vessel wall properties in relation to cerebral white matter lesions in myocardial infarction patients

Objective

Atherosclerotic large vessel disease is potentially involved in the pathogenesis of cerebral small vessel disease related to occurrence of white matter lesions (WMLs) in the brain. We aimed to assess morphological and functional carotid vessel wall properties in relation to WML using magnetic resonance imaging (MRI) in myocardial infarction (MI) patients.

Materials and methods

A total of 20 MI patients (90 % male, 61 ± 11 years) underwent carotid artery and brain MRI. Carotid vessel wall thickness (VWT) was assessed, by detecting lumen and outer wall contours. Carotid pulse wave velocity (PWV), a measure of elasticity, was determined using the transit-time method. Patients were divided according to the median VWT into two groups. Brain MRI allowed for the WML score.

Results

Mean VWT was 1.41 ± 0.29 mm and mean carotid PWV was 7.0 ± 2.2 m/s. A significant correlation (Pearson r = 0.45, p = 0.046) between VWT and PWV was observed. Furthermore, in the group of high VWT, the median WML score was higher as compared with the group with lower VWT (4.0 vs 3.0, p = 0.035).

Conclusions

Carotid artery morphological and functional alterations are correlated in MI patients. Patients with high VWT showed a higher amount of periventricular WMLs. These findings support the hypothesis that atherosclerotic large vessel disease is potentially involved in the pathogenesis of cerebral small vessel disease.     

Association between risk of oral precancer and genetic variations in microRNA and related processing genes

Background

MicroRNAs have been implicated in cancer but studies on their role in precancer, such as leukoplakia, are limited. Sequence variations at eight miRNA and four miRNA processing genes were studied in 452 healthy controls and 299 leukoplakia patients to estimate risk of disease.

Results

Genotyping by TaqMan assay followed by statistical analyses showed that variant genotypes at Gemin3 and mir-34b reduced risk of disease [OR = 0.5(0.3–0.9) and OR = 0.7(0.5–0.9) respectively] in overall patients as well as in smokers [OR = 0.58(0.3–1) and OR = 0.68(0.5–0.9) respectively]. Among chewers, only mir29a significantly increased risk of disease [OR = 1.8(1–3)]. Gene-environment interactions using MDR-pt program revealed that mir29a, mir34b, mir423 and Xpo5 modulated risk of disease (p < 0.002) which may be related to change in expression of these genes as observed by Real-Time PCR assays. But association between polymorphisms and gene expressions was not found in our sample set as well as in larger datasets from open access platforms like Genevar and 1000 Genome database.

Conclusion

Variations in microRNAs and their processing genes modulated risk of precancer but further in-depth study is needed to understand mechanism of disease process.     

Longevity-associated mitochondrial DNA 5178 C/A polymorphism modulates the effects of coffee consumption on erythrocytic parameters in Japanese men: an exploratory cross-sectional analysis

Background

Mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism reportedly modulates the effects of coffee consumption on the risk of hypertension, dyslipidemia and abnormal glucose tolerance. The objective of this analysis was to investigate whether Mt5178 C/A polymorphism modifies the effects of coffee consumption on erythrocytic parameters in male Japanese health check-up examinees.

Methods

A total of 436 men (mean age ± standard deviation, 54.1 ± 7.8 years) were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, an exploratory cross-sectional analysis assessing the joint effects of Mt5178 C/A polymorphism and coffee consumption on red blood cell counts, hematocrit and hemoglobin was conducted.

Results

For Mt5178C genotypic men, after adjustment for age, body mass index, alcohol consumption, habitual smoking and green tea consumption, coffee consumption significantly decreased red blood cell counts (P for trend = 0.022) and hemoglobin (P for trend = 0.035). The risk of anemia, defined as hemoglobin of <14 g/dL, after the aforementioned adjustment, appeared to depend on coffee consumption (P for trend = 0.078), and the adjusted odds ratio for anemia was significantly higher in men who consumed ≥4 cups of coffee per day than in those who consumed <1 cup per day (odds ratio = 3.771, 95% confidence interval: 1.088 to 13.06, P = 0.036). For Mt5178A genotypic men, coffee consumption possibly reduced the risk of anemia (P for trend = 0.049). However, after the aforementioned adjustment, the statistical significance disappeared (P for trend = 0.137).

Conclusions

This exploratory cross-sectional analysis suggests that Mt5178 C/A polymorphism modulates the effects of coffee consumption on erythrocytic parameters and the risk of anemia in male Japanese health check-up examinees.     

The prevalence and identity of Chlamydia-specific IgE in children with asthma and other chronic respiratory symptoms

Background

Recent studies have confirmed the presence of viable Chlamydia in the bronchoalveolar lavage (BAL) fluid of pediatric patients with airway hyperresponsiveness. While specific IgG and IgM responses to C. pneumoniae are well described, the response and potential contribution of Ag-specific IgE are not known. The current study sought to determine if infection with Chlamydia triggers the production of pathogen-specific IgE in children with chronic respiratory diseases which might contribute to inflammation and pathology.

Methods

We obtained BAL fluid and serum from pediatric respiratory disease patients who were generally unresponsive to corticosteroid treatment as well as sera from age-matched control patients who saw their doctor for wellness checkups. Chlamydia-specific IgE was isolated from BAL and serum samples and their specificity determined by Western blot techniques. The presence of Chlamydia was confirmed by species-specific PCR and BAL culture assays.

Results

Chlamydial DNA was detected in the BAL fluid of 134/197 (68%) patients. Total IgE increased with age until 15 years old and then decreased. Chlamydia-specific IgE was detected in the serum and/or BAL of 107/197 (54%) patients suffering from chronic respiratory disease, but in none of the 35 healthy control sera (p < 0.0001). Of the 74 BAL culture-positive patients, 68 (91.9%, p = 0.0001) tested positive for Chlamydia-specific IgE. Asthmatic patients had significantly higher IgE levels compared to non-asthmatics (p = 0.0001). Patients who were positive for Chlamydia DNA or culture had significantly higher levels of serum IgE compared to negative patients (p = 0.0071 and p = 0.0001 respectively). Only 6 chlamydial antigens induced Chlamydia-specific IgE and patients with C. pneumoniae-specific IgE had significantly greater levels of total IgE compared to C. pneumoniae-specific IgE negative ones (p = 0.0001).

Conclusions

IgE antibodies play a central role in allergic inflammation; therefore production of Chlamydia-specific IgE may prove significant in the exacerbation of chronic, allergic airway diseases, thus highlighting a direct role for Chlamydia in asthma pathogenesis.     

Gene-gene interaction analysis identifies a new genetic risk factor for colorectal cancer

Background

Adiponectin levels have been shown to be associated with colorectal cancer (CRC). Furthermore, a newly identified adiponectin receptor, T-cadherin, has been associated with plasma adiponectin levels. Therefore, we investigated the potential for a genetic association between T-cadherin and CRC risk.

Result

We conducted a case–control study using the Korean Cancer Prevention study-II cohort, which is composed of 325 CRC patients and 977 normal individuals. Study results revealed that rs3865188 in the 5’ flanking region of the T-cadherin gene (CDH13) was significantly associated with CRC (p = 0.0474). The odds ratio (OR) for the TT genotype as compared to the TA + AA genotype was 1.577 (p = 0.0144). In addition, the interaction between CDH13 and the adiponectin gene (APN) for CRC risk was investigated using a logistic regression analysis. Among six APN single nucleotide polymorphisms (rs182052, rs17366568, rs2241767, rs3821799, rs3774261, and rs6773957), an interaction with the rs3865188 was found for four (rs2241767, rs3821799, rs3774261, and rs6773957). The group with combined genotypes of TT for rs3865188 and GG for rs377426 displayed the highest risk for CRC development as compared to those with the other genotype combinations. The OR for the TT/GG genotype as compared to the AA/AA genotype was 4.108 (p = 0.004). Furthermore, the plasma adiponectin level showed a correlation with the gene-gene interaction, and the group with the highest risk for CRC had the lowest adiponectin level (median, 4.8 μg/mL for the TT/GG genotype vs.7.835 μg/mL for the AA/AA genotype, p = 0.0017).

Conclusions

The present study identified a new genetic factor for CRC risk and an interaction between CDH13 and APN in CRC risk. These genetic factors may be useful for predicting CRC risk.

Electronic supplementary material

The online version of this article (doi:10.1186/s12929-015-0180-9) contains supplementary material, which is available to authorized users.Keyword: Gene-gene interaction, CRC, CDH13, rs3865188, APNSNPs     

Recurrence-associated pathways in hepatitis B virus-positive hepatocellular carcinoma

Background

Despite the recent identification of several prognostic gene signatures, the lack of common genes among experimental cohorts has posed a considerable challenge in uncovering the molecular basis underlying hepatocellular carcinoma (HCC) recurrence for application in clinical purposes. To overcome the limitations of individual gene-based analysis, we applied a pathway-based approach for analysis of HCC recurrence.

Results

By implementing a permutation-based semi-supervised principal component analysis algorithm using the optimal principal component, we selected sixty-four pathways associated with hepatitis B virus (HBV)-positive HCC recurrence (p < 0.01), from our microarray dataset composed of 142 HBV-positive HCCs. In relation to the public HBV- and public hepatitis C virus (HCV)-positive HCC datasets, we detected 46 (71.9%) and 18 (28.1%) common recurrence-associated pathways, respectively. However, overlap of recurrence-associated genes between datasets was rare, further supporting the utility of the pathway-based approach for recurrence analysis between different HCC datasets. Non-supervised clustering of the 64 recurrence-associated pathways facilitated the classification of HCC patients into high- and low-risk subgroups, based on risk of recurrence (p < 0.0001). The pathways identified were additionally successfully applied to discriminate subgroups depending on recurrence risk within the public HCC datasets. Through multivariate analysis, these recurrence-associated pathways were identified as an independent prognostic factor (p < 0.0001) along with tumor number, tumor size and Edmondson’s grade. Moreover, the pathway-based approach had a clinical advantage in terms of discriminating the high-risk subgroup (N = 12) among patients (N = 26) with small HCC (<3 cm).

Conclusions

Using pathway-based analysis, we successfully identified the pathways involved in recurrence of HBV-positive HCC that may be effectively used as prognostic markers.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1472-x) contains supplementary material, which is available to authorized users.