DNA ploidy and expression of P53, cMyc in childhood leukemia's and their families

Chromosomal abnormalities in childhood leukemia have important biological, diagnostic and prognostic significance. The genes that are associated with the development of malignancy were categorized as oncogenes and tumor suppressor genes. P53 belongs to the category of tumor genes and is located on the short arm of chromosome 17 p13. It is a specific transcriptional activator of genes controlling GI checkpoint of the cell cycle and controls the expression of certain genes involved in the control of programmed cell death [Apoptosis]. cMyc gene is Juxtaposed with one of the immunoglobulin genes: heavy chain on 14[q32], kappa on 2[p12] or Iambda on 22[q11]. In pediatric ALL with translocation of ch.,8 [q24] onch., 14[q32] or ch22[q11], c-Myc expression is markedly deregulated by the highly active immunoglobulin locus. This leads to an increase in c-Myc max dimmers and transactivation of multiple cognate target genes, driving uncontrolled cellular proliferation. This study was designed to determine the DNA content [ploidy], expression P53 protein and c-Myc protein in children with acute lymphoblastic leukemia as well as in their first degree relatives [parents and siblings] in order to detect the role of these proteins in the developing of leukemia and those at risk of developing leukemia This study was done on 20 infants and children [16 males and 4 females], their age ranged from 2 to 12 years. They were admitted to the Hematology Unit at Mansoura University Children Hospital where they were diagnosed as acute lymphoblastic leukemia [ALL] and were taken at presentation before induction of treatment. Their first-degree relatives were also included in the study [20 fathers, 20 mothers and 44 siblings [23 brothers and 21 sisters]].Twenty healthy persons with negative family /history of cancers, their aye range from 4 to 30 years, were taken as control group. All the studied subjects were subjected to isolation of lymphocyte which staining and fixation within 24 hours from sampling where DNA analysis by flow cytometer was done. The results proved that 60 % of the cases with acute lymphoblastic leukemia were hyper diploid [DWA index >1.0] and 10 % were hypo diploid [DNA index [1.0]. All of their leukemic children were DNA aneuploid while 10 % of tile-studied parents had DNA aneuploid positive cells and 7% of the healthy siblings had DNA aneuploid positive cells. A high significant level of p53 protein in patients with ALL when compared with healthy controls [p<0.0001], a significant difference in between patients with ALL and their first -degree relative regarding P53 protein. Also a significant difference in between the first-degree relative and healthy controls regarding p53 [p=<0.0001]. The results of this study also showed significant difference in the level of expression of p53 protein among patients with DNA aneuploidy cells compared to those with DNA diploid patients. A significant difference in patients with ALL when compared with healthy controls, also were was significant difference in first degree relatives of leukemia patients versus to healthy controls regarding the level of c-Myc protein [p=<0.0001]. 80 % of parents and 77 % of siblings between the first-degree relative expressing high levels of cMyc protein

Conclusion: genetic alterations play an important role in the development of childhood leukemia particularly mutation of p53 tumor suppressor gene and cMyc gene where the level of expression of their related protein is high. Also change in the DNA content of the lymphoblast's of majority of the patients with acute lymphoblastic leukemia appears to be constant feature. These changes not only present in cases with ALL but also in their first degree relatives suggesting that there is a vertical transmission of these genes in these families. First -degree relatives of leukemia patients particularly those with abnormal DNA and those expressing high level of p53 protein and cMyc protein are at high risk of developing cancers must be subjected for close follow up

Growth in children with chronic renal failure and transplantation

Growth retardation is major problem for many children with chronic renal failure [CRF] and transplantation. The aim of this study is to assess the relation between height, glomerular filtration rate [GFR], hormonal alterations in children with CRF on regular hemodialysis [EID] and the impact of normal graft function after kidney transplantation Eighteen children with mean age of 10.5623.08 years suffered from CRF maintained on HD were included in the study beside 16 children [mean age 11.06 +/- 3.19yr] enjoyed normal graft function after transplantation Mean duration on HD was 14.72 +/- 7.73 months for CRF group while, mean interval after transplantation was 1.97 +/- 0.9 yews for the second group. Moreover, ten healthy children of matched age and sex were served as control. Assessment of growth parameters including height, expressed as standard deviation scores [HtSDS] for chronological age, measurement of serum growth hormone [hGH] and serum parathormone [PTH] by radioimmunoassay. Growth performance was evaluated twice: at the start of the study and one year later. Both categories with CRF and transplantation had significantly higher levels of serum hGH and PTH compared to their control [P<0.001] while CRF children had significantly higher serum levels of hGH and PTH compared to those with normal graft function [P<0.008 and P<0.001 respectively]. Furthermore, analysis of our results by non-parametric Kendall's correlation at the start and one year later revealed negative correlation concerning dialysis duration, serum creatinine and PTH. On the other hand, positive correlation was achieved for serum calcium and GFK

Conclusion: growth retardation in children with CRF despite the normal or elevated hGH level may be explained by the presence of peripheral ; insensitivity to the action of hGH

comparison of different physiological mortality risk prediction scores in critically III children in pediatric intensive care unit

This is a prospective observational study, comparing between three general physiology based prognostic scoring systems, which have been primarily developed to measure severity of illness and predict patient's outcome in pediatric intensive care unit [PICU]: Pediatric index of Mortality score [PIM], Pediatric Risk of Mortality score [PRISM] using both the original and current coefficients; in addition to evaluating the type and number of Organ System Failure [OSF]. The main goal was to assess the performance of each score. We prospectively collected data of 750 patients [447 males and 303 females] consecutively admitted to PICU with crude mortality rate of 5.6%. The study demonstrated that PIM score had good performance as evidenced by good discrimination and calibration in both the overall population as well as in two different subgroups [neonates and nonsurgical], but not in surgical, in addition to it is free and simple to use. It has also been demonstrated that PRISM score [original coefficients] had a poor performance in the overall population, as well as in nonsurgical and neonates but not in surgical subgroup. Meanwhile, PRISM [current coefficients] score showed good performance in the overall population, as well as in two subgroups [surgical and non surgical] but not in neonates. This is indicating the need to update and recalibrate prognostic scoring systems to maintain good performance over time. The new coefficients used in PRISM [current coefficients] in this study to compute mortality risk estimates were just developed to show the change in mortality risk over time and do not constitute a new pediatric mortality prediction scoring system. This study found also that organ system failure [OSF] is an important independent risk factor of death and patients with multiple organ system failure [two or more organ system failures] are more likely to die than those with one or less organ system failure

Epidermal growth factor in human breast milk

Human Breast milk contains a group of bioactive growth factors. They play a role in maturation of several organs like liver, brain, kidney, and intestine. Among these factors, the Epidermal growth factor [EGF]. The purpose of the present study was to compare the concentration of EGF in different human milk samples obtained from Egyptian mothers delivered at full term and preterm. Human milk samples were collected from two groups of lactating mothers, the first group comprised 30 mothers who delivered at full term and the second group were 30 mothers who delivered at preterm. The concentration of EGF in human milk samples was measured by radioimmunoassay. Milk samples were collected from 3 to 10 days after delivery. The results showed that breast milk from the mothers in the first group had a significantly lower EGF concentration compared to that from mothers in the second group [P < 0.0017]. EGF in human breast milk negatively correlated with the gestational age of the neonates in the two studied groups with r = -0.726 and P < 0.006 for the first group; and r =- 0.933 and P < 000014 for the second group

Conclusion: Our results suggest that higher EGF level in the preterm infant mother's milk is a compensatory mechanism to push and support the growth, differentiation and functional maturation of many organs in the preterm infant. From our study and similar previous researches, we can conclude that premature infants could benefit more from their own mother's milk than from pooled human milk

Assessment of pressure gradients by doppler echo-cardiography versus cardiac catheterization in congenital heart disease

The aim of the present work is to assess the accuracy and validity of Doppler estimated pressure gradients in a variety of congenital heart diseases. 156 infants and children with obstructive cardiac lesions or ventricular septal defect had been seen at Christ Hospital and Medical Center, Chicago Illinois during a 22 month period from July 1993 to April 1995. There were [74-boys and 82-girls], ranging in age from 1 day to 15.8 years, and in weight from 1.8- 59Kg. A careful history and physical examination were done for all cases. Complete blood picture was done to all cases and it was normal. 12 leads ECG, chest X-ray, 2 - dimensional Doppler echocardiography and cardiac catheterization were obtained in all patients. The study confirmed that Doppler echocardiography has predictive value for assessing gradient severity in right ventricular outflow obstruction irrespective whether the obstruction occurs at the valvular, subvalvular, or supravalvular level and whether it is isolated [r=0.82] or associated with other lesions [r=0.94]. In patients with severe valvular pulmonary-stenosis the correlation between Doppler derived and catheterization measured pressure gradients was significantly low [r = 0.69, SEE +/- 10.75 mmHg]. We found a statistically significant difference between Doppler gradients measured under sedation [r = 0.94, SEE +/- 6.49 mm Hg] and those measured without sedation [r= 0.88. SEE + 10.48 mm Hg]. The correlation coefficient of Doppler-derived pressure gradients obtained within 24 hours after BVP and those obtained after 24 hours were comparable [r = 0.84, 0.80 respectively] In patients with aortic stenosis we found excellent correlation between the catheterization peak-to-peak gradient and the Doppler maximal instantaneous gradient [r= 0.96 SEE +/- 6.57] and in patients with aortic coarctation the correlation coefficient was 0.94 [SEE +/- 6.12]. For cases with VSD the correlation coefficient was 0.80 [SEE +/- 15.4 mm Hg]. In study of 19 patients [43 percent] with pressure gradients > 64 mm Hg [small defect] determined by-cardiac catheterization. The correlation was relatively poor [r= 0.63, SEE +/- 9.92 mm Hg]. We concluded that Doppler echocardiography is a reliable, simple, and noninvasive outpatient procedure for the quantification of transvalvular gradients in patients with congenital heart disease. Doppler echocardiography can provide an accurate assessment of the severity of stenosis. However, Doppler echocardiography has many limitations. Pressure gradient measurements is falsely higher in sedated children than alert ones. Doppler gradient measurements in an alert and unsedated patient may be a better measure of the true physiological state. Also the reliability of Doppler echocardiography in accurately measuring the pressure gradient is unsatisfactory in very severe valvular stenosis with systemic or suprasystemic right ventricular systolic pressure. Moreover, the size of the VSD defect and the direction of the intracardiac shunting seem to be the main factors affecting Doppler diagnostic performance. The accuracy of Doppler echocardiography may be affected by the nutritional status of the patients

Anticardiolipin antibodies in children under chronic hemodialysis efficacy

IgG and IgM anticardiolipin antibodies [aCL] concentrations were determined in serum samples of 48 children with ESRD on hemodialysis using ELISA technique in an attempt to analyze their possible role in the occurrence of thrombosis of the vascular access. 10 normal healthy children were studied as a control group. The positivity of both IgG-aCL and IgM-aCL isotypes were high in hemodialysis patients. The mean values of GPL units was 25.7 +/- 10 and 9.4 +/- 3.1 for MPL units. Children with positive levels of aCL had significantly more prior thrombosis of vascular access. A strong negative correlation between platelet count and positive aCL titers was found. Negative correlation was also appeared between platelet count and occurrence of fistula thrombosis. Elevated positive levels of aCL are common in children with ESRD on hemodialysis and should be interpreted as markers of risk for fistula thrombosis, and may be useful in prediction of subsequent vascular occlusive events