Association of Intermittent and Continuous Hypoxaemia with Carotid and Brachial Arterial Intima-Media Thicknesses

ABSTRACT Objective: To assess the carotid and brachial arteries' intima-media thicknesses (IMTs) in cases with intermittent (obstructive sleep apnoea syndrome (OSAS)) and continuous (chronic obstructive pulmonary disease (COPD)) hypoxaemia together with other confounding demographic and biochemical factors. Methods: The study was prospectively performed on 197 patients allocated in three groups: 80 with severe OSAS, 80 with severe COPD patients and 37 healthy controls. These groups were compared in terms of demographics, biochemical markers and IMTs of the right and left carotid and brachial arteries. Results: Carotid and brachial arterial IMTs were found to be higher in both patient groups than the control group (p < 0.001). Similarly, levels of haemoglobin, haematocrit, cholesterol, triglycerides, low-density lipoproteins (LDL), C-reactive protein and D (domain)-dimer were significantly increased in patient groups. Oxygen saturations (p < 0.001) and ejection fractions (p = 0.001) were found to be worse and D-dimer levels (p = 0.010) were elevated more prominently in COPD patients, whereas, cholesterol (p < 0.001), hemoglobin (p = 0.004) and LDL (p = 0.001) levels were higher in the OSAS group. Except the right carotid IMT, which was increased significantly in OSAS patients, IMT measurements were similar in the OSAS and COPD groups (p < 0.001). Conclusion: We have shown that both intermittent and continuous hypoxia result in remarkable alterations in carotid IMT and brachial IMT. Further prospective trials are warranted to confirm and extend these findings, including the biochemical markers, which may aid in the diagnosis and follow-up of patients suffering from hypoxaemia.

Revealing Alzheimer's disease genes spectrum in the whole-genome by machine learning.

BACKGROUND: Alzheimer's disease (AD) is an important, progressive neurodegenerative disease, with a complex genetic architecture. A key goal of biomedical research is to seek out disease risk genes, and to elucidate the function of these risk genes in the development of disease. For this purpose, expanding the AD-associated gene set is necessary. In past research, the prediction methods for AD related genes has been limited in their exploration of the target genome regions. We here present a genome-wide method for AD candidate genes predictions. METHODS: We present a machine learning approach (SVM), based upon integrating gene expression data with human brain-specific gene network data, to discover the full spectrum of AD genes across the whole genome. RESULTS: We classified AD candidate genes with an accuracy and the area under the receiver operating characteristic (ROC) curve of 84.56% and 94%. Our approach provides a supplement for the spectrum of AD-associated genes extracted from more than 20,000 genes in a genome wide scale. CONCLUSIONS: In this study, we have elucidated the whole-genome spectrum of AD, using a machine learning approach. Through this method, we expect for the candidate gene catalogue to provide a more comprehensive annotation of AD for researchers.

Targeted next-generation sequencing analysis identifies novel mutations in families with severe familial exudative vitreoretinopathy.

PURPOSE: Familial exudative vitreoretinopathy (FEVR) is a genetically and clinically heterogeneous disease, characterized by failure of vascular development of the peripheral retina. The symptoms of FEVR vary widely among patients in the same family, and even between the two eyes of a given patient. This study was designed to identify the genetic defect in a patient cohort of ten Chinese families with a definitive diagnosis of FEVR. METHODS: To identify the causative gene, next-generation sequencing (NGS)-based target capture sequencing was performed. Segregation analysis of the candidate variant was performed in additional family members by using Sanger sequencing and quantitative real-time PCR (QPCR). RESULTS: Of the cohort of ten FEVR families, six pathogenic variants were identified, including four novel and two known heterozygous mutations. Of the variants identified, four were missense variants, and two were novel heterozygous deletion mutations [LRP5, c.4053 DelC (p.Ile1351IlefsX88); TSPAN12, EX8Del]. The two novel heterozygous deletion mutations were not observed in the control subjects and could give rise to a relatively severe FEVR phenotype, which could be explained by the protein function prediction. CONCLUSIONS: We identified two novel heterozygous deletion mutations [LRP5, c.4053 DelC (p.Ile1351IlefsX88); TSPAN12, EX8Del] using targeted NGS as a causative mutation for FEVR. These genetic deletion variations exhibit a severe form of FEVR, with tractional retinal detachments compared with other known point mutations. The data further enrich the mutation spectrum of FEVR and enhance our understanding of genotype-phenotype correlations to provide useful information for disease diagnosis, prognosis, and effective genetic counseling.

Effects of lowered dialysate sodium on left ventricle function and brain natriuretic peptide in maintenance of hemodialysis patients.

INTRODUCTION: Impaired diastolic flow is characterized by decreased left ventricular (LV) filling diastole, abnormal LV distensibility, or delayed relaxation. B-Type natriuretic peptide (BNP) is an indicator of various cardiovascular diseases and body volume status. The aim of this study was to determine whether the lowering of dialysate sodium (Na) levels is effective on LV systolic and diastolic parameters and BNP in the maintenance of hemodialysis patients. MATERIALS AND METHODS: The study included 49 chronic hemodialysis patients. Left atrium (LA) diameter and LV ejection fraction, LV systolic and diastolic diameter, deceleration time (DT), pulmonary artery pressure (PAP), inferior vena cava diameter (IVCD), early diastolic transmitral flow ( E) and late diastolic transmitral flow ( A) velocities, E/ A ratio, isovolumic relaxation time, peak early diastolic velocity ( E'), late diastolic velocity ( A') of tissue Doppler mitral annulus, and flow propagation velocity of mitral inflow ( Vp) were measured before and 6 months after hemodialysis with low Na dialysate. RESULTS: Six months after low Na hemodialysis, a decrease was observed in echocardiographic parameters such as PAP and IVCD ( p < 0.05, p < 0.001, and p < 0.001, respectively). However, a significant difference was not observed in LA diameter. In LV diastolic measurement of E and A waves, E/ A ratio, DT, Vp, septal E' and A', and lateral E' and A' exhibited significant improvement by low Na HD. BNP level was significantly reduced ( p < 0.001). CONCLUSIONS: Lowered dialysate Na concentration improves PAP, IVCD, and LV diastolic properties assessed by mitral inflow filling, tissue Doppler velocity, and mitral inflow velocity propagation.

Experimentally induced hyperthyroidism influences oxidant and antioxidant status and impairs male gonadal functions in adult rats.

The objective of the present experiment was to study the effect of hyperthyroidism on male gonadal functions and oxidant/antioxidant biomarkers in testis of adult rats. Induction of hyperthyroidism by L-thyroxine (L-T4, 300 µg kg(-1) body weight) treatment once daily for 3 or 8 weeks caused a decrease in body weight gain as well as in absolute genital sex organs weight. The epididymal sperm counts and their motility were significantly decreased in a time-dependent manner following L-T4 treatment. Significant decline in serum levels of luteinising hormone, follicle stimulating hormone and testosterone along with significant increase in serum estradiol level was observed in hyperthyroid rats compared with euthyroid ones. Significant increase in malondialdehyde and nitric oxide concentration associated with significant decrease in superoxide dismutase and catalase activity was also noticed following hyperthyroidism induction. Both reduced glutathione content and glutathione peroxidase activity were increased in hyperthyroid rats compared with control rats. Marked histopathological alterations were observed in testicular section of hyperthyroid rats. These results provide evidence that hypermetabolic state induced by excess level of thyroid hormones may be a causative factor for the impairment of testicular physiology as a consequence of oxidative stress.

Effect of ramipril therapy on abnormal left atrial appendage function.

This study investigated whether ramipril treatment has a beneficial effect on left atrial appendage (LAA) function in patients with systemic hypertension in sinus rhythm. Patients with untreated systemic hypertension and normal left ventricular systolic function in sinus rhythm (n = 20; six males/14 females; age 35 - 69 years, mean ± SD 52.8 ± 8.9 years) were evaluated using transthoracic and transoesophageal echocardiography at baseline and after 6 months of treatment with 5 mg/day ramipril. Mean systolic and diastolic blood pressures decreased significantly after ramipril therapy. Baseline LAA emptying velocity was below the age-related reference value for this parameter, indicating abnormal LAA function. There were significant increases in the LAA filling and emptying velocities after ramipril treatment. It is concluded that the decrease in blood pressure and haemodynamic improvements brought about by ramipril therapy resulted in improved LAA function in hypertensive patients with normal left ventricular systolic function in sinus rhythm.

Transesophageal echocardiography assessment of left atrial appendage function in untreated systemic hypertensive patients in sinus rhythm.

To assess left atrial appendage (LAA) function in hypertensive patients without treatment, transesophageal echocardiography (TEE) was performed in 46 hypertensive patients in sinus rhythm, aged 40 to 55 years, and in 16 control subjects (group I) without cardiovascular disease, aged 41 to 54 years. The hypertensive patients were divided into 2 groups according to left ventricular (LV) systolic function: group II, the group with normal LV systolic function (ejection fraction 0.63 +/- 0.08), and group III, the group with LV systolic dysfunction (ejection fraction 0.39 +/- 0.05). The LAA late emptying velocities (EVs) were significantly reduced in the hypertensive subgroups compared with the control group (P <.001), but no significant difference in the LAAEV was found between groups II and III. The LAAEV in the hypertensive patients had a significant negative correlation with diastolic blood pressure, systolic blood pressure, and left atrial (LA) diameter. The maximal LAA areas were significantly larger in the hypertensive subgroups than in the control group (P <.05). No significant difference in LAA maximal area existed between groups II and III. The maximal LAA area in the hypertensive patients had a significant positive correlation with diastolic blood pressure, systolic blood pressure, and LA diameter, but a significant negative correlation with LV ejection fraction. With TEE, LA spontaneous echocardiographic contrast (SEC) was present in 6 (43%) of 14 patients in group III (P <.01) and in 7 (22%) of 32 patients in group II (P <.05). No significant difference in the occurrence of LASEC was found between groups II and III. Left atrial appendage thrombi by TEE were observed in 4 (29%) of 14 patients in group III (P <.05) and in 4 (13%) of 32 patients in group II (P = not significant). No significant difference in the occurrence of LAA thrombus existed between groups II and III. In conclusion, in patients with untreated hypertension, marked elevation of afterload imposed on the left atrium may involve both the left atrium and the LAA, resulting in impairment of LAA function. This condition may worsen with subsequent occurrence of SEC and later, thrombus formation. Therefore assessment of LAA function may be important even in the hypertensive patient in sinus rhythm.

Frequency of left atrial thrombus and spontaneous echocardiographic contrast in acute myocardial infarction.

Left ventricular systolic dysfunction may precipitate blood stasis as well as thrombus formation in the left atrial appendage of patients with acute myocardial infarction, even in the presence of sinus rhythm. Thus, left atrial thrombi may be an alternative source for systemic embolism in acute myocardial infarction.

Evaluation of right atrial appendage blood flow by transesophageal echocardiography in subjects with a normal heart.

Right atrial appendage (RAA) blood flow pattern was analyzed in 42 normal subjects-without cardiovascular disease (aged 30 to 48 years, mean 40 +/- 6) who underwent transesophageal echocardiography. RAA flow pattern was demonstrated to be bi-, tri- or quadriphasic and heart rate dependent (p < 0.01) in this study. In 15 subjects (36%), a biphasic pattern was observed. A triphasic pattern was observed in 12 subjects (28%). Fifteen subjects (36%) had a quadriphasic pattern. In these subjects, we observed a pattern consisting of two diastolic forward flow waves, each followed by a backward flow wave. Mean heart rates among subjects with bi-, tri- and quadriphasic patterns were 110 +/- 6, 91 +/- 4 and 72 +/- 13 beats/min, respectively. In the triphasic pattern, the onset of superior vena cava diastolic forward flow began 18 +/- 4 ms after the onset of tricuspid E wave, whereas the first diastolic forward flow wave in the RAA began 40 +/- 7 ms after onset of the tricuspid E wave. A similar relation was also noted in the quadriphasic pattern. This sequence was constant and independent of heart rate (p < 0.05), suggesting a temporal relation between right ventricular relaxation and the first diastolic forward flow wave in the RAA. In normal subjects, the RAA flow pattern is heart rate dependent and three distinct flow patterns can be differentiated. Right ventricular relaxation appears to induce both the superior vena cava diastolic forward flow wave and the first diastolic forward flow wave of the RAA. These results can be used for comparison with patterns found in disease states.