Effect of Estrogen Receptor- Alpha Gene Polymorphism (IVS1-397 T>C) on Microvascular Complications of Type 1 Diabetes Mellitus.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is an autoimmune disease whose etiology involves genetic predisposition as well as environmental factors. Polymorphisms of some genes are among the most important genetic factors that influence autoimmunity. Gender is another important factor affecting autoimmunity. Females are more susceptible to autoimmune diseases which may be due to the effect of sex hormones on the immune system activity. The metabolic effects of estrogen are mediated through its receptor - alpha. The exact mechanism is not well understood. A number of polymorphisms have been reported in the Estrogen Receptor- alpha (ER-alpha) IVS1 397 T>C gene which may be involved in the pathogenesis of diabetes. OBJECTIVES: To assess the influence of Estrogen Receptor- alpha gene [IVS1-397 T>C] polymorphism on vascular complications of type1 diabetes mellitus in pubertal females and on the glycemic control. METHODS: This cross-sectional case-control study included 40 pubertal regularly menstruating girls less than 18 years with type 1 diabetes mellitus recruited from the Pediatric Diabetes Clinic, Children's Hospital, Ain-Shams University and 20 healthy age-and sex-matched controls. Estrogen receptor alpha genotypes were analyzed by Restriction Fragment Length PCR and correlated with both clinical and laboratory parameters in the studied cases. ER-alpha was chosen as it might play a role in diabetes pathogenesis. RESULTS: The study revealed the TC genotype was the most prevalent genotype of the estrogen receptor. The TT genotype patients had a younger age of onset of T1DM. The prevalence of obesity was higher among TC and TT than in CC bearing patients. In addition, CC genotype patients had the least prevalence of microalbuminuria and had better glycemic control than other genotypes. CONCLUSION: Our findings suggest that Estrogen receptor- alpha gene may be affecting the age of onset of Type1 diabetes mellitus in pubertal girls as well as the glycemic control of these patients, where CC bearing girls had better glycemic control than other genotypes and less incidence of microalbuminuria.

A prospective study of the hypothalamic-pituitary-adrenal axis in children with acute lymphoblastic leukemia receiving chemotherapy.

BACKGROUND: Glucocorticoids are essential in protocols of therapy of acute lymphoblastic leukemia (ALL). OBJECTIVES: To assess the incidence, severity, morbidity, and risk factors of hypothalamic-pituitary-adrenal axis (HPA) suppression in children with ALL, and the time course of recovery. DESIGN: Forty standard risk ALL children treated in the Pediatric Hematology/Oncology Unit, Ain-Shams University, Egypt, were classified into dexamethasone (DXM) group: 20 patients on children cancer group protocol and prednisone (PDN) group: 20 patients on modified Berlin-Frankfurt-Muenster (BFM) study group 90 protocol. Patients were followed clinically and by laboratory assessment of morning s.ACTH, basal and after low-dose adrenocorticotrophic hormone stimulation test of cortisol and DHEAS, at diagnosis and every 2 weeks till adrenal recovery. RESULTS: HPA recovery was earlier in PDN than DXM group (P < 0.05). In induction phases 1 and 2: 65 and 75% of PDN group recovered on week 2, while 45 and 50% of DXM group recovered in week 4. Adrenal recovery was predicted 2 weeks earlier by normalized s.DHEAS. Children below 5 years of age had earlier recovery in PDN group (P = 0.04), no age effect in DXM group. CONCLUSION: Adrenal suppression is an inevitable consequence of ALL therapy. Monitoring of cortisol levels and steroid coverage during stress is recommended, and gradual steroid tapering is suggested.

Radionuclide ventriculography detects early anthracycline cardiotoxicity in children with Hodgkin lymphoma.

Serial echocardiography to detect doxorubicin dose-related cardiotoxicity correlates poorly with endomyocardial biopsy-proven cardiotoxicity. To compare radionuclide ventriculography (RVG) and echocardiography for the assessment of left ventricular (LV) function in children with Hodgkin disease (HD) receiving doxorubicin, we studied 39 children with HD before radiotherapy, both early (≤ 2 adriamycin, bleomycin, vinblastine, and dacarbazine cycles) (group A; n=10) and late (≥ 6 adriamycin, bleomycin, vinblastine, and dacarbazine cycles) (group B; n=36) during treatment. Seven children were assessed twice. The patients underwent full clinical assessment, echocardiography, and RVG. In group A, LV ejection fraction (LVEF) was significantly lower when measured by RVG compared with echocardiography (P<0.05). Group B had lower LVEF compared with group A by echocardiography (P=0.09), and by RVG (P=0.000). Paired analysis of children studied early and late showed a significant drop in LVEF by echocardiography (58.7 ± 7.3 vs. 52 ± 52.44%; P=0.04) and RVG (51.4 ± 2.6% vs. 47.2 ± 3.1%; P=0.004). The cumulative dose of doxorubicin inversely correlated with RVG-measured LVEF (r=-0.531; P=0.001). No correlation was found between LVEF measured by RVG and echocardiography (r=0.217; P=0.25). Cardiotoxicity occurred early and at low cumulative doses of doxorubicin in children with HD. RVG was more sensitive than echocardiography in detecting early impairment of LV function. We recommend baseline and serial assessment of LV function by RVG in children with HD receiving doxorubicin.