Heart rate variability in beta‐thalassemia patients

Background: Cardiac failure remains the major cause of death in beta‐thalassemia major (TM). Reduced heart rate variability (HRV) is associated with a higher risk of arrhythmias after myocardial infarction and heart failure. We evaluated HRV in TM patients and its relationship with hemodynamics and echocardiographic parameters during a 6‐month follow‐up. Methods: Thirty‐four TM patients (19 ± 10 yr) and 20 healthy subjects (17 ± 6 yr) were evaluated. Hematologic, biochemical, echocardiographic and HRV parameters were determined at entry and at 6‐month follow‐up. Time and frequency domain HRV parameters were analyzed from 24‐h recorded electrocardiograms. All TM patients received blood transfusion and chelation therapy. Results: Both time and frequency domain HRV parameters were markedly reduced in TM patients, compared to the control. The significantly improved HRV was seen in correlation with higher hemoglobin (Hb) level when compared within TM group at different time point. No correlation was seen between HRV and serum ferritin, reactive oxygen species (ROS) and non‐transferrin bound iron (NTBI). Conclusion: HRV is depressed in TM patients. HRV was significantly correlated with Hb level, suggesting that anemia greatly influences the cardiac autonomic balance.     

Fetal hemoglobin Bart’s hydrops fetalis: pathophysiology,prenatal diagnosis and possibility of intrauterine treatment

This review aimed at comprehensively summarizing current available reports regarding the ultrasound markers and biomarkers in predicting fetal Hb Bart’s disease and evaluate the potential role of cardiac function assessment in a clinical practice. This review involves various methods in prenatal predicting fetal Hb Bart’s disease or alpha-thalassemia major and attempts to provide valuable insights regarding the underlying mechanisms responsible for heart failure in Hb Bart’s fetuses. Moreover, this information may be used to predict the cardiac function before the development of hydrops fetalis. Finally, the affected Hb Bart’s fetus could be the best model of the study on cardiovascular response to fetal anemia, thus the cardiovascular ultrasound and molecular assessment may be helpful in predicting the prognosis or in making a choice in the management of the fetal anemia condition. In conclusion, ultrasound findings especially cardiomegaly and an increase in peak systolic velocity of the middle cerebral artery (MCA-PSV) are helpful in predicting the future hydrops fetalis and ultrasound assessment of fetal cardiac function is potentially helpful in clinical practice. Finally, this review highlights the pathogenesis of hydropic changes secondary to fetal anemia.     

Relationships between serum biomarker levels and clinical presentation of human osteosarcomas

Background: Currently, serum biomarkers play an important role as sensitive tools for monitoring the cancer development and progression. Each biomarker represents a specific pathogenesis and has different predictive capability. In order to identify their characteristics in human osteosarcoma, multiple potential biomarkers were analyzed simultaneously with clinical presentations. Materials and Methods: Blood samples were collected from 28 osteosarcoma patients and 30 healthy matched controls. Specific clinical presentations were recorded, including: tumor volume, estimated based on three-dimensional MRI volumetric measurement; metastasis status; and histological cell types. Serum biomarkers analyzed by ELISA-based assays were bone-specific alkaline phosphatase (BALP), vascular endothelial growth factor (VEGF), hyaluronic acid (HA) and chondroitin sulfate WF6 (WF6). Serum lactate dehydrogenase (LDH) was analyzed by a photometric-based system. Results: Serum BALP, LDH and WF6 levels of osteosarcoma patients were significantly higher than those of healthy controls, whereas HA and VEGF levels were not significantly different between the two groups. Serum BALP and LDH were positively correlated with tumor volume, (correlation coefficients 0.5 and 0.4, respectively). Serum BALP from metastasis and osteoblastic subtype group had a significantly higher level than that found in non-metastasis and non-osteoblastic subtypes group, respectively. Upon multivariate analysis, tumor volume was the only factor which correlated with BALP levels. Conclusion: Of the biomarkers analyzed in this study, serum BALP was the most reliable and sensitive for estimating tumor volume. A high level of serum WF6 reflects alteration of the extracellular matrix component of tumors. Both serum biomarkers can be expected to be further explored for use in specific clinical monitoring.     

Lack of prognostic significance of HER-2/neu in early epithelial ovarian cancer

A total of 74 patients with apparent early stage epithelial ovarian cancer who underwent exploratory laparotomy at King Chulalongkorn Memorial Hospital or other hospitals and were referred for further treatment, were evaluated. Formalin fixed paraffin-embedded ovarian tissue specimens were collected and immuno-stained with HER-2/neu antibodies for comparison with clinicopathologic data after median follow up of 46 months (range 3 - 83 months). The prevalence of HER-2/neu overexpression in these patients was 10.2%. No significant correlation between HER-2/neu overexpression and clinicopathological parameters (stage, ascites, capsular rupture, capsular adherence, histological subtype and histological grade) was found. Disease free survival and overall survival did not statistically differ between those with lesions positive or negative for HER-2/neu overexpression.     

Antiarrhythmic effects of n-3 polyunsaturated fatty acids

The n-3 or omega 3 polyunsaturated fatty acids are a promising dietary preventive therapy for cardiovascular disease. The main dietary source of n-3 polyunsaturated fatty acids comes from sea fish. During recent years, the subject of antiarrhythmic role of n-3 polyunsaturated fatty acids has been investigated extensively. A great deal of evidence has shown that the antiarrhythmic effect of n-3 polyunsaturated fatty acids is exerted by altering the electrophysiology of myocytes. This article is intended to review specifically this role of n-3 polyunsaturated fatty acids as demonstrated by both basic and clinical evidence in animal and human studies, including current concepts on the antiarrhythmic mechanism of this class of polyunsaturated fatty acids.     

Serial echocardiographic left ventricular ejection fraction measurements: A tool for detecting thalassemia major patients at risk of cardiac death

Cardiac damage remains a major cause of mortality among patients with thalassemia major. The detection of a lower cardiac magnetic resonance T2* (CMR-T2*) signal has been suggested as a powerful predictor of the subsequent development of heart failure. However, the lack of worldwide availability of CMR-T2* facilities prevents its widespread use for follow-up evaluations of cardiac function in thalassemia major patients, warranting the need to assess the utility of other possible procedures. In this setting, the determination of left ventricular ejection fraction (LVEF) offers an accurate and reproducible method for heart function evaluation. These findings suggest a reduction in LVEF ≥ 7%, over time, determined by 2-D echocardiography, may be considered a strong predictive tool for the detection of thalassemia major patients with increased risk of cardiac death. The reduction of LVEF ≥ 7% had higher (84.76%) predictive value. Finally, Kaplan–Meier survival curves of thalassemia major patients with LVEF ≥ 7% showed a statistically significant decreased probability of survival for heart disease (p = 0.0022).However, because of limitations related to the study design, such findings should be confirmed in a large long-term prospective clinical trial.     

DPP4‐inhibitor improves neuronal insulin receptor function,brain mitochondrial function and cognitive function in rats with insulin resistance induced by high‐fat diet consumption

High‐fat diet (HFD) consumption has been demonstrated to cause peripheral and neuronal insulin resistance, and brain mitochondrial dysfunction in rats. Although the dipeptidyl peptidase‐4 inhibitor, vildagliptin, is known to improve peripheral insulin sensitivity, its effects on neuronal insulin resistance and brain mitochondrial dysfunction caused by a HFD are unknown. We tested the hypothesis that vildagliptin prevents neuronal insulin resistance, brain mitochondrial dysfunction, learning and memory deficit caused by HFD. Male rats were divided into two groups to receive either a HFD or normal diet (ND) for 12 weeks, after which rats in each group were fed with either vildagliptin (3 mg/kg/day) or vehicle for 21 days. The cognitive function was tested by the Morris Water Maze prior to brain removal for studying neuronal insulin receptor (IR) and brain mitochondrial function. In HFD rats, neuronal insulin resistance and brain mitochondrial dysfunction were demonstrated, with impaired learning and memory. Vildagliptin prevented neuronal insulin resistance by restoring insulin‐induced long‐term depression and neuronal IR phosphorylation, IRS‐1 phosphorylation and Akt/PKB‐ser phosphorylation. It also improved brain mitochondrial dysfunction and cognitive function. Vildagliptin effectively restored neuronal IR function, increased glucagon‐like‐peptide 1 levels and prevented brain mitochondrial dysfunction, thus attenuating the impaired cognitive function caused by HFD.     

Heart rate variability and exercise capacity of patients with repaired tetralogy of Fallot

Heart rate variability (HRV) has been used as a reliable method to detect cardiac autonomic nervous system activity. Peak oxygen uptake (VO₂ peak) has been a predictor of death for adults with repaired tetralogy of Fallot (TOF). This study investigated the correlation between HRV and exercise capacity in 30 patients with TOF after surgery for total correction. The median age of the patients was 14 years (range, 9–25 years), and the median follow-up period was 11.6 months (range, 5.3–20.2 months). Low- and high-frequency-domain HRV significantly correlated with VO₂ peak (r = 0.56, P = 0.001 and r = 0.44, P = 0.02, respectively). After the 1-year follow-up evaluation, VO₂ peak and HRV analysis did not differ from those at entry to the study. However, low- and high-frequency-domain HRV still correlated significantly with VO₂ peak (r = 0.43, P = 0.03 and r = 0.52, P = 0.007, respectively). Left ventricular early diastolic myocardial velocity was most closely correlated with the VO₂ peak (r = 0.51, P = 0.005). Impaired cardiovascular autonomic control and left ventricular diastolic dysfunction may be responsible for exercise intolerance in patients with repaired TOF. Long-term follow-up evaluation with exercise testing and 24-h Holter monitoring are warranted.