Expression of CD4+ CD28null T lymphocytes in children and adolescents with type 1 diabetes mellitus: Relation to microvascular complications, aortic elastic properties, and carotid intima media thickness.

BACKGROUND: Cardiovascular risk in type 1 diabetes mellitus (T1DM) is associated with endothelial dysfunction, inflammation, and altered immunity. CD4+ CD28null T-cells are a subset of long-lived cytotoxic CD4+ T-lymphocytes with proatherogenic and plaque-destabilizing properties. We hypothesized that the frequency of CD4+ CD28null T-cells may be altered in T1DM and related to vascular complications. AIM: To assess the percentage of CD4+ CD28null T-lymphocytes in children and adolescents with T1DM and their relation to vascular structure and glycemic control. METHODS: Totally 100 patients with T1DM were divided into 2 groups according to the presence of microvascular complications and compared with 50 healthy controls. CD4+ CD28null T-lymphocytes were analyzed using flow cytometry. Aortic elastic properties and carotid intima media thickness (CIMT) were assessed. RESULTS: Aortic stiffness index and CIMT were significantly higher among patients compared with healthy controls while aortic strain and distensibility were decreased. The percentage of CD4+ CD28null T-cells was significantly higher in patients with and without microvascular complications compared with controls. High frequency of CD4+ CD28null T-cells was found among patients with microalbuminuria or peripheral neuropathy. Patients with CD4+ CD28null T-cells ≥10% had higher HbA1c, urinary albumin creatinine ratio, aortic stiffness, and CIMT. CD4+ CD28null T-cells were positively correlated to HbA1c, aortic stiffness index, and CIMT. CONCLUSIONS: Changes in aortic elastic properties and increased CIMT among young patients with T1DM may enable the recognition of preclinical cardiac impairment. The correlation between CD4+ CD28null T-cells and assessed parameters of vascular structure highlights the role of altered immune response in the occurrence of diabetic vascular complications.

Glutathione S-transferase gene polymorphism: Relation to cardiac iron overload in Egyptian patients with Beta Thalassemia Major.

OBJECTIVES: Estimating the prevalence of glutathione S-transferase gene polymorphism (GSTM1) null genotype among patients with beta thalassemia major (ß-TM) in relation to myocardial status assessed by tissue Doppler and cardiac siderosis assessed by cardiac magnetic resonance imaging (MRI) T2*. METHODS: Hundred patients with ß-TM and 100 healthy controls were enrolled. Complete blood count (CBC), mean serum ferritin and GSTM1 genotyping, echocardiography, tissue Doppler, and cardiac MRI T2* were done. RESULTS: Serum ferritin ranged from 1200 to 8000 ng/ml, and mean T2* value was 27.10 ± 11.20 ms. Of patients, 68 (68%) had no cardiac siderosis, while 24 (24%) with mild to moderate, and 8 (8%) with sever cardiac siderosis. T2* values were not correlated with serum ferritin (r = -0.09, P = 0.50). GSTM1 null genotype was prevalent in 46% of patients and 40% of controls (P = 0.69). Patients with null genotype had significantly shorter T2* (P = 0.001), higher left ventricular end-diastolic diameter (P = 0.002), and shorter ejection time (P = 0.005) with no significant relation to serum ferritin (P = 0.122). GSTM1 null genotype was the only predictor for cardiac iron overload (P = 0.002). DISCUSSION: Serum ferritin concentrations have been shown to correlate poorly with all stages of cardiac dysfunction. Low cardiac MRI T2* values occur in patients with ß-TM despite good chelation therapy, suggesting a possible role of genetic factors in cardiac siderosis. CONCLUSION: GSTM1 null genotype is significantly associated with cardiac iron overload independent of serum ferritin in Egyptian patients with ß-TM.

Flow cytometric assessment of circulating platelet and erythrocytes microparticles in young thalassemia major patients: relation to pulmonary hypertension and aortic wall stiffness.

Heart disease is the leading cause of mortality and morbidity in ß-thalassemia major (ß-TM). Aggregability of abnormal red cells and membrane-derived microparticles (MPs) stemming from activated platelets and erythrocytes are responsible for thrombotic risk. We measured platelet and erythrocyte MPs (PMPs and ErMPs) in 60 young ß-TM patients compared with 40 age- and sex-matched healthy controls and assessed their relation to clinicopathological characteristics and aortic elastic properties. Patients were studied stressing on transfusion history, splenectomy, thrombotic events, chelation therapy, hematological and coagulation profiles, flow cytometric measurement of PMPs (CD41b(+) ) and ErMPs (glycophorin A(+) ) as well as echocardiographic assessment of aortic elastic properties. Aortic stiffness index and pulmonary artery pressure were significantly higher, whereas aortic strain and distensibility were lower in TM patients than controls (P < 0.001). Both PMPs and ErMPs were significantly elevated in TM patients compared with controls, particularly patients with risk of pulmonary hypertension, history of thrombosis, splenectomy or serum ferritin >2500 µg/L (P < 0.001). Compliant patients on chelation therapy had lower MPs levels than non-compliant patients (P < 0.001). PMPs and ErMPs were positively correlated to markers of hemolysis, serum ferritin, D-dimer, vWF Ag, and aortic stiffness, whereas negatively correlated to hemoglobin level and aortic distensibility (P < 0.05). We suggest that increased MPs may be implicated in vascular dysfunction, pulmonary hypertension risk, and aortic wall stiffness observed in thalassemia patients. Their quantification could provide utility for early detection of cardiovascular abnormalities and monitoring the biological efficacy of chelation therapy.

Atrial natriuretic peptide as a marker of heart failure in children with left ventricular volume overload.

AIM: To evaluate the role of atrial natriuretic peptide (ANP) in differentiating the aetiology of heart failure in children with left ventricular (LV) volume overload. METHODS: The study was conducted on 48 patients with LV volume overload (G one: rheumatic heart disease in failure; G2: compensated rheumatic heart disease; G3: congenital left to right shunt; and G4: dilated cardiomyopathy). Twelve healthy children served as a control group. New York Heart Association (NYHA) class, LV dimensions and functions using Vivid 7 dimensions were evaluated. Serum ANP was measured using the ELISA technique, before and 3 months after treatment with angiotensin converting enzyme inhibitor. RESULTS: ANP was raised in all patients as compared to controls (G one: 28.33 ± 5.78, G2: 26.5 ± 4.11, G3: 28.5 ± 6.6, G4: 29.25 ± 4.5 pg/mL, control group: 5.54 ± 1.4 pg/mL, P < 0.001 for all) and varied significantly between different NYHA classes regardless of the underlying cardiac lesion. It was significantly higher in group 1 than 2 (P < 0.05). It decreased significantly after treatment (G1: 15.3 ± 5.3, G2: 10.7 ± 2.5, G3: 11.5 ± 3.8, G4: 15.7 ± 10.7 pg/mL, P < 0.001). The rate of change of ANP correlated with that of LV end diastolic diameter (r = 0.3, P < 0.05) irrespective of the underlying cause. CONCLUSION: ANP increases in cases of LV volume overload irrespective of the aetiology of heart failure. It can differentiate between children in quiescent state from those in clinical failure even in the absence of echocardiographically detectable systolic dysfunction. Furthermore, it can monitor LV remodelling with treatment.

Therapeutic role of mobilized bone marrow cells in children with nonischemic dilated cardiomyopathy.

Dilated cardiomyopathy is an important cause of congestive cardiac failure in infants and children. Mobilizing hematopoietic progenitor cells is a promising intervention to this deadly disease. Aim. Evaluate granulocyte colony stimulating factor (GCSF) as therapeutic modality in children with idiopathic dilated cardiomyopathy (IDCM). Subjects and Methods. This case-control prospective study was conducted on 20 children with IDCM following up at Cardiology Clinic Children's Hospital, Ain Shams University (group 1) who were compared to another 10 age-, sex-, duration-of-illness-, and systolic-function-matched children with IDCM as control (group 2). They were subjected to history taking, clinical examination, echocardiography, and peripheral blood CD34+ cell assessment before and one week after GCSF intake for 5 consecutive days (by group 1 but not group 2). Results. A significant improvement in echocardiographic data and CD34+-T-cell increase was found in group 1 one week after GCSF intake and for the next 6 months CD34+ T cells percentage of change showed no significant correlation with the that of the left ventricular dimensions and systolic function. Conclusion. Administration of GCSF to children with IDCM resulted in clinical and echocardiographic improvement not correlated to mobilized CD34+ T cells, implying involvement of additional mechanisms over simple stem cell mobilization.

Ongoing inflammation in children with rheumatic heart disease.

AIM OF THE WORK: To elucidate the hypothesis of ongoing inflammation in children with chronic rheumatic heart disease, and its possible consequences. SUBJECTS AND METHODS: This study was conducted on 36 patients with a mean age of 12.63 years: six with acute rheumatic carditis, and 30 with chronic rheumatic heart disease. There were 15 age- and sex-matched children who served as a control group. All subjects underwent echocardiographic assessment of valvular involvement and left ventricular function. Laboratory investigations comprised lipid profile, high-sensitivity C-reactive protein, and homocysteine assay. RESULTS: High-sensitivity C-reactive protein was significantly elevated in patients with acute rheumatic carditis and in patients with chronic rheumatic heart disease (mean and standard deviation of 78.33, 156 micrograms per millilitre and 78.33, 23.17 micrograms per millilitre, respectively) as compared to the control group (mean and standard deviation of 5.83 and 2.79 micrograms per millilitre). High-sensitivity C-reactive protein correlated with the grade of mitral regurgitation (p less than 0.05). Homocysteine was significantly elevated in patients with acute carditis and patients with rheumatic heart disease as compared to the control group (their mean and standard deviation were 2.96, 0.476 nanograms per decilitre, 2.99, 1.48 nanograms per decilitre, and 1.717, 0.733 nanograms per decilitre, respectively), but did not show significant difference between the two studied groups of patients. Neither C-reactive protein nor homocysteine correlated with any of the studied parameters of lipid profile. CONCLUSION: There is evidence of ongoing inflammation in children with rheumatic heart disease, which correlates with the degree of valvular involvement. This ongoing inflammation may put those children at risk for premature atherosclerosis.