Endothelial Dysfunction Linked to Ventricular Dysfunction in Children With Sickle Cell Disease, a 3D Speckle Tracking Study.

Background: Sickle Cell Disease (SCD) is not a hematologic disease that occurs in isolation; it results in multi-organ complications. There is growing evidence of vascular stiffness as its underlying cause. This study aimed to investigate the relationship between endothelial stiffness and LV dysfunction in SCD patients and to explore its pathophysiology, particularly regarding the depletion of vasodilators such as Nitric Oxide (NO). Methodology: 32 patients with established criteria for SCD and 40 healthy control subjects were selected for this case-control study. Comprehensive clinical assessment and assessment of endothelial function using Brachial Flow-mediated dilation (FMD) were performed, along with serum NO measurement, which was followed by diagnosis and echocardiographic assessment using 3D speckle tracking echocardiography (STE) and tissue Doppler imaging (TDI). Results: Collected SCD cases showed echocardiographic features of Systo-diastolic dysfunction with reduced FMD compared to controls, denoting endothelial dysfunction in those patients. LDH showed a marked elevation, while serum NO showed a significant reduction in cases compared with controls. We also noted a positive correlation between FMD on the one hand and measures of ventricular dysfunction and level of serum NO on the other hand, the latter proving that reduction of NO is responsible for reduced endothelial function. Conclusion: We present the first report to date to outline the role of vascular stiffness as measured by brachial FMD in the induction of left ventricular dysfunction in SCD. We recommend that more research be conducted regarding possible strategies to replenish serum NO stores to delay microvascular injury and, in turn, ventricular dysfunction in SCD.

Short-term effects of corticosteroid therapy on cardiac and skeletal muscles in muscular dystrophies.

BACKGROUND: Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy of childhood. It leads to progressive deterioration in cardiac and skeletal muscles. Corticosteroids are considered an effective therapy. OBJECTIVE: This study aimed to evaluate the role of short-term prednisone therapy in improving left ventricular (LV) systolic function, LV mass (LVM), and motor power in cases of muscular dystrophies. PATIENTS AND METHODS: Twenty-five cases of muscular dystrophy including 17 cases of DMD, 3 cases of Becker muscular dystrophies, and 5 cases of female patients with DMD-like phenotype were included in the study. The diagnosis of 12 patients was confirmed by muscle biopsy with immunohistochemistry; the patients were subjected to motor assessment, measurement of creatine kinase level, and echocardiographic examination before and after prednisone therapy. Transthoracic echocardiographic assessment of the LV systolic function (fractional shortening) was done. Myocardial performance index and LVM were calculated. Intermittent dosage of prednisone was administered 5 mg/kg per day on 2 consecutive days weekly for 3 months. RESULTS: Fractional shortening improved on prednisone therapy (P = 0.009) and LVM increased (P = 0.012); improvement in walking was detected in 77% of the patients, climbing stairs improved in 88.9%, Gower sign improved in 70%, and rising from chair improved in 60%. Prednisone had no effect on the patients with marked motor impairment (on wheelchair). The creatine kinase level was significantly lower after steroid therapy (P = 0.04). CONCLUSIONS: Three months of intermittent prednisone therapy could improve cardiac and skeletal muscle function in congenital muscular dystrophy.

Echocardiogram done early in neonatal sepsis: what does it add?

BACKGROUND: One of the major organs affected in neonatal sepsis is the heart. Echocardiogram provides real-time information on the cardiovascular performance rather than dependence on the clinical signs alone, which might lead to misjudgment. AIM OF THE WORK: To assess left ventricular (LV) functions in septic neonates early after admission using transthoracic color Doppler Echocardiography. PATIENTS AND METHODS: Echocardiography was done to 30 septic and 30 nonseptic newborns who were divided among 4 groups (septic full-term, 14; septic preterm, 16; nonseptic full-term, 21; and nonseptic preterm, 9). Comparisons were made among the 4 groups using analysis of variance and post hoc test regarding the systolic function (using ejection fraction and fractional shortening), the diastolic function (using the early patrial peak/atrial peak flow velocity ratio), and the global LV function (using myocardial performance index). RESULTS: The E-wave and the early peak flow velocity/atrial peak flow velocity ratio were significantly lower in the septic neonates, whether full-term or premature, compared to their corresponding age groups in the nonseptic newborns, suggesting LV diastolic dysfunction (P < 0.001 and P < 0.014, respectively). No difference was found in the diastolic function between the full-term and the preterm neonates whether lying within the septic group or in the nonseptic group. Myocardial performance index was significantly higher in the septic neonates who died than in the survivors (P < 0.001). CONCLUSION: Neonatal sepsis is associated with LV diastolic dysfunction.

Transforming growth factor-beta1 gene C-509T and T869C polymorphisms as possible risk factors in rheumatic heart disease in Egypt.

OBJECTIVE: The objective of this study was to investigate the possible relationship between the TGF-beta1 gene C-509T and T869C polymorphisms and rheumatic heart disease (RHD), as well as their clinical significance. METHODS: Seventy-three patients with RHD diagnosed by echocardiography (mean age 31.7 +/- 14.7 y, male: female ratio 20:53) and, fifty-five age and sex-matched unrelated healthy volunteers (normal control) were included. Patients were classified according to age into children (n=24, mean age 14.4 +/- 3.1 y, and adults (n=49, mean age 40.2 +/- 9.9 y). TGF-beta genomic DNA was extracted and amplified using primers specific for C-509T and,T869C polymorphisms. Genotyping was performed by restriction fragment length polymorphism analysis (RFLP). RESULTS: T869C TT genotype was found significantly more frequently in RHD (total population) (OR: 3.27; [95% CI: 1.13-9.46]; P = 0.02), in children (OR: 6.0; [95% CI: 1.74-20.65]; P = 0.002) and in patients with combined valvular disease (CVD) (OR: 4.06; [95% CI: 1.32-12.48]; P = 0.01) compared to control subjects. 869T allele frequency was significantly higher in adults (OR: 1.89; [95% CI: 1.07-3.33]; P = 0.02), children (OR: 2.32; [95% CI: 1.16-4.66]; P = 0.0 1) and the total population (OR: 2.02; [95% CI: 1.21-3.39]; P = 0.006). C-509T genotypes distributions were not different between RHD patients and control subjects. However, -509T allele seems to confer susceptibility to RHD (OR: 1.78; [95% CI: 1.02-3.11]; P = 0.04). Both adults and children showed no significant difference in the genotypes distribution and allelic frequencies of TGF-beta1 C-509T polymorphism. In addition, genotype distribution and allelic frequencies of C-509T or T869C did not have any relation with the severity of the valvular affection. CONCLUSION: TGF-beta1 T869C TT genotype, 869T allele and 509T allele are possible risk factor for RHD in Egypt. Future studies on larger populations are warranted.

Doppler assessment of brachial artery flow as a measure of endothelial dysfunction in pediatric chronic renal failure.

Cardiovascular morbidity and mortality are highly prevalent among patients with chronic renal failure (CRF). Endothelial dysfunction is regarded as the initial reversible step in the development of atherosclerosis and has been demonstrated in all stages of renal failure. Non-invasive techniques to assess endothelial function have been recently developed and have been proven to predict future mortality in adults. We aimed to assess endothelial function in children with stage 4 chronic kidney disease (CKD 4) on conservative treatment, using a-non invasive, high-resolution, ultrasound Doppler study of the brachial artery flow, correlating it with other clinical and laboratory parameters. This study included 34 children with CKD 4 on conservative treatment who were compared with 30 healthy controls. Flow-mediated dilatation (FMD), nitroglycerin-mediated dilatation (NTG-MD) and FMD/NTG-MD ratio were estimated. FMD was abnormal (< 5%) in 24 patients (71%). FMD and FMD/NTG-MD ratio were significantly lower in patients than in controls (P = 0.001 and P = 0.01, respectively). FMD correlated positively with serum calcium and negatively with alkaline phosphatase. We concluded that endothelial dysfunction is present in children with CKD 4 on conservative treatment and may reflect increased atherogenic and thrombogenic properties of the endothelium, contributing to subsequent adverse cardiovascular outcome.

Rapid detection of beta-Thalassemia alleles in Egypt using naturally or amplified created restriction sites and direct sequencing: a step in disease control.

beta-Thalassemia (thal), the most common genetic disorder in Egypt, is a major health problem with an estimated carrier rate of 9-10%. This study, aimed at describing the beta-globin gene mutations in the Suez Canal area, an important Egyptian region, to provide a foundation for a disease control program. We studied 44 beta-thalassemic patients (and their relatives) from 35 families living in this region. The commonest mutations were genetically diagnosed using naturally or amplified created restriction sites. Less frequent mutations were characterized by denaturing gradient gel electrophoresis (DGGE) and direct sequencing. Twelve different mutations were identified in 51 unrelated chromosomes. The three most frequent mutations were IVS-I-110 (G-->A), IVS-I-1 (G-->A) and IVS-I-6 (T-->C). The spectrum of rarer mutations was heterogeneous and differed from that reported in other areas of Egypt. We also identified the first homozygous case of a rare mutation, codon 24 (-G; +CAC), displaying a thalassemia major phenotype. Parental consanguinity was high (60.6%) with 35.7% of the compound heterozygous patients having consanguineous parents. These data provide insights for the distribution of beta-thal alleles in this region, and could be used as a basis for genetic counseling and prenatal diagnosis.