Expression of some apoptosis-controlling proteins in children with acute lymphoblastic leukemia

The aim of this study was to determine the serum levels of some apoptosis-controlling proteins [Bcl-2 and soluble Fas] in children with acute lymphoblastic leukemia [ALL], and to find out the relation between their expression and the clinico-laboratory parameters as well as outcome of the disease. The study included 20 children with ALL [13 males and 7 females], their age ranged from 0.5-13 years. Twelve apparently healthy children were included as a control group. Cases and controls were subjected to full history taking, thorough clinical examination, and determination of serum levels of Bcl-2 and soluble Fas proteins [sFas], and complete blood picture [CBC]. Bone marrow examination, CSF examination, immunophenotyping, and radiological evaluation were done for cases only. One-year follow-up of cases was performed for evaluation of the prognosis and the outcome of the disease. The results showed that serum levels of Fas and Bcl-2 were significantly elevated in patients with ALL when compared to control [P: 0.007 and P: 0.003 respectively]. Serum levels of sFas were significantly elevated in cases with CNS involvement compared to those without CNS involvement [p <0.01], in cases with white blood cell count >50.000/mm[3] in peripheral blood compared to those having lower cell counts [p<0.05], and in patients with T cell lineage compared to those with B lineage [p<0.01]. Serum levels of Bcl-2 were not significantly different as regard these parameters. Serum levels of Bcl-2 were significantly lowered after treatment [P<0.001], while serum sFas didn't differ significantly before and after treatment. Levels of sFas and Bcl-2 were higher in ALL patients resistant to induction chemotherapy compared to those showing complete remission, but the difference did not reach the level of significance. Our study shows that 1] increased serum expression of Bcl-2 and soluble Fas [sFas] can be demonstrated in children with ALL. 2] increased expression of sFas [but not Bcl-2] has been found to be associated with certain unfavorable prognostic features such as T-lineage ALL, CNS involvement, and higher WBCs count and 3] the higher levels of sFas and Bcl-2 in these cases were not associated with poor response to therapy

Role of thrombopoietin and plasma erythropoietin in neonatal sepsis

The objectives is to evaluate the role of thrombopoietin [Tpo] and esythropoietin [Epo], as reliable indicators of neonatal sepsis and the value of rhuEpo in improving the outcome of septic neonates. A prospective study was conducted on 120 sick neonates with sepsis. Sixty two [51.7%] were fullterms and 58 [48.3%] were preterms with a mean gestational age of 32.8. +/- 2.9 weeks. The mean birth weight was 2.7 +/- 0.98 Kg and the mean age of sampling was 5.5 +/- 1.9 days. Sixty neonates received treatment with rhuEpo in addition to the classic therapy of sepsis for 10-14 days. Another group of 60 septic neonates received the classic therapy of sepsis only for 10-14 days. Thirty healthy neonates, age and sex matched with the study groups, were served as a control group. Serum Tpo and Epo levels were measured by ELISA [enzyme-linked immunosorbent assay]. Significant higher differences of serum Tpo and Epo levels were found between septicemic neonates and control group [P<0.001]. The higher the septic score, the higher the serum levels. Septicemic neonates with DIC had significantly higher serum Tpo levels than septicemic neonates without DIC [216.42 +/- 66.5 pg/ml, 172.69 +/- 62.4 pg/ml P=0.042]. Also, septicemic neonates with pallor had significantly higher serum Epo levels than those without pallor [24.1 +/- 7.4 IU/ml, 20.3 +/- 5.2 IU/ml, P=0.022]. On admission, the serum Tpo levels ranged between 39-344 pg/ml with a mean +/- SD of 173.76 +/- 62.67 pg/ml and was statistically significant when compared with control group [32-114 pg/ml, 69.63 +/- 21.4 pg/ml, P=0.001]. After improvement, the serum Tpo levels ranged between 29-133 pg/ml with a mean of 74.5 +/- 25.3 pg/ml and insignificant difference when compared with control group [P=0.37]. Serum Epo levels at the onset [21.14 +/- 6.28 IU/ml] and after improvement [8.81 +/- 3.71 IU/ml] were significantly higher [0.001 and 0.009 respectively] when compared to controls [6.73 +/- 2.9 IU/ml]. Septicemic neonates who received treatment with rhuEpo in addition to the classic therapy showed significantly lower mortality rate [18 patients died, 30%] than those who received the classic therapy only [34 patients died. 56.7%], P=0.003. Serum Tpo and Epo levels are increased in neonates with sepsis, the higher the septic score, the higher the serum levels of both markers. Increase in serum Epo levels during neonatal septicemia is a multifactorial process rather than affecting the haemostatic mechanisms only. The use of rhuEpo in management of septicemic cases could improve the outcome of septicemic patients and decrease the mortality rate

Growth in children with chronic renal faliure and after transplantation

This study aimed at studying the relation between height, glomerular filtration rate [GFR] and hormonal alteration in children with chronic renal failure [CRF] on regular hemodialysis [HD] and the possible role of normal graft function, after kidney transplantation, in this respect. The study population comprised 18 children with CRF on HD with mean age of 10.56 +/- 3.08 years and 16 children with normal graft function [mean age 11.06 +/- 3.19]. Mean duration on HD was 14.72 +/- 7.73 months for CRF group. Mean interval after transplantation was 1.97 +/- 0.9 years for the group of functioning grafts. Ten normal healthy children of matched age and sex served as controls. All patients were subjected to 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 after a period of one year. The overall growth retardation in children with CRF on HD corresponded to -3.16 +/- 0.43 [mean SDS for height]. Children with normal graft function had a mean HtSDS of -2.54 +/- 0.29. Growth retardation remained a critical complication after kidney transplantation despite the statistically significant improvement observed compared to the group of children with CRF [P< 0.001]. Our results confirmed that impaired HtSDS with children with CRF correlates with the duration on hemodialysis [r = -0.728, P< 0.001]. There was a significant correlation between GFR and PTH level [r = -0.750, P< 0.001] in children with CRF. Our series of children with CRF had a positive correlation between their SDS for height and GFR [r =0.760 with P<0.001]. Both categories with CRF and with normal graft function had significantly higher levels of both serum hGH and PTH compared to controls [P<0.001], while CRF children had significantly higher serum levels of both hGH and PTH compared to those with normal graft function [P<0.008 and P<0.001 respectively]. Our results support the possibility that 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

Diagnosis and genetic susceptibility of pulmonary tuberculosis in children

This study consisted of 3 closely related parts; the first part included 70 children with pulmonary tuberculosis [TB], aged 2 - 10 years and 20 healthy children as controls. All were subjected to thorough history taking, clinical examination, chest x-ray and tuberculin test. Blood samples were taken to perform glutaraldehyde test and for detection of IgG antibodies against mycobacterium TB by ELISA technique using antigen A60. The sensitivity of glutaraldehyde test was 87.1% and its specificity was 90% with high significance, while the sensitivity of ELISA test was 48.6% and its specificity was 90%. In the second part of the study, sputum samples from 57 children recently diagnosed as having pulmonary tuberculosis, were processed for microscopic examination of smears after staining for acid fast bacilli, culture on Lowenstein-Jensen medium and nested polymerase chain reaction [PCR]. Patients included in this part were divided into 3 groups. In a group of 20 children not-receiving antituberculous therapy yet, the results of smear examination and PCR were identical in 75% of cases. In 10% of cases culture was most sensitive, but in 25% of patients nested PCR was positive even when smear and culture were negative. In a group of 20 children receiving antituberculous therapy for less than six months, PCR positive results were obtained even when both smear and culture were negative. In a group of 17 children receiving antituberculous therapy for more than six months, positive PCR results were detected up to the 7[th] month of therapy. The third part of the study included the HLA [A, B, C loci] phenotyping in 25 cases out of 70 studied in the first-part, and 92 controls. The results showed higher frequency of the following HLA antigens among cases of pulmonary TB than the controls: A25[10], A26[10], AW66, B35, BW55, CW3, CW4 and CW5, and associated with increased relative risk [RR] above one and the etiologic factor for CW4 antigen was 0.408. On the other hand HLA- B5+ B18+ B35, B12, B27 were significantly higher among the controls than the cases. We concluded that glutaraldehyde test can be used as simple, rapid, inexpensive, not tedious test and was positive in cases of TB with malnutrition. Concerning ELISA test, it can be used as rapid serodiagnostic test which is reliable and relatively inexpensive technique for diagnosis of active pulmonary TB in children. Application of nested PCR assay could be used as a follow-up tool in monitoring of pulmonary tuberculosis in children. Regarding HLA antigens the results showed high frequency of the previously mentioned HLA antigens with pulmonary TB, which may indicate, increased susceptibility to pulmonary TB infection. On the other hand, high frequency of other mentioned HLA antigens among controls may indicate a protective effect of these antigens. Anyhow further studies are still needed to be done and on a wide scale to prove the association of HLA antigens and tuberculosis

High dose intravenous immunoglobulin therapy in neonatal immune hemolytic jaundice

Isoimmune hemolytic jaundice due to blood group [ABO] and Rhesus [Rh] incompatibility is an important problem in the neonatal period. A controlled study was conducted to assess the role of high dose intravenous immunoglobulin [HDIVIG] therapy in neonatal immune hemolytic jaundice. Newborn patients with ABO and/or Rh incompatibilities proved by significant hyperbilirubinemia [>15mg/dl], positive direct Coombs' test and high reticulocytic count [>6%] were randomly assigned to receive either conventional treatment measures alone, including phototherapy and exchange transfusion if needed [control group, n=10 newborns] or phototherapy with high dose i.v. immunoglobulin [1gm/kg] over 4 hours [study group, n=30 newborns] as soon as the diagnosis was established. One of the 30 patients in the HDIVIG group required exchange transfusion, while this became necessary in 3 of 10 patients in the control group [p<0.001]. The duration of phototherapy and hospitalization, in terms of hours were significantly shorter in the HDIVIG group [p<0.001]. No adverse effects of HDIVIG therapy were observed. The use of HDIVIG therapy in newborns with ABO and/or Rh hemolytic disease reduces hemolysis, serum bilirubin levels, the need for blood exchange transfusion and the duration of hospitalization

Clinico-laboratory study of pulmonary tuberculosis in children

This study consisted of 3 closely related parts, the first part included 70 children with pulmonary Tuberculosis [TB], aged 2 - 10 years and 20 healthy children as controls. All were subjected to thorough history taking, clinical examination, chest x-ray and tuberculin test. Blood samples were taken to perform glutaraldehyde test and for detection of IgG antibodies against mycobacterial TB by ELISA technique using antigen A60. The sensitivity of glutaraldehyde test was 87.1% and its specificity was 90% with high significance, while the sensitivity of ELISA test was 48.6% and its specificity was 90%. In the second part of the study, sputum samples from 57 children recently diagnosed as having pulmonary tuberculosis, were processed for microscopic examination of smears after staining for acid fast bacilli, culture on Lowenstein-Jensen medium and nested polymerase chain reaction [PCR]. Patients included in this part were divided into 3 groups. In a group of 20 children not-receiving antituberculous therapy yet, the results of smear examination and PCR were identical in 75% of cases .In 10% of cases culture was most sensitive, but in 25% of patients nested PCR was positive even when smear and culture were negative .In a group of 20 children receiving antituberculous therapy for less than six months, PCR positive results were obtained even when both smear and culture were negative. In a group of 17 child receiving antituberculous therapy for more than six months, positive PCR results were detected up to the 7[th] month of therapy. The third part of the study included the HLA [A, B, C loci] phenotyping in 25 cases out of 70 studied in the first part, and 92 controls. The results showed higher frequency of the following HLA antigens among cases of pulmonary TB than the controls [A25[10], A26[10], AW66, B35, BW55, CW3, CW4 and CW5] and associated with increased relative risk [RR] above one and the etiologic factor for CW4 antigen was 0.408. On the other hand HLA- B5+ B18+ B35, B12, B27 were significantly higher among the controls than the cases. We concluded that glutaraldehyde test can be used as simple, rapid, inexpensive, not tedious test and was positive in cases of TB with malnutrition, concerning ELISA test it can be used as rapid serodiagnostic test which is reliable and relatively inexpensive technique for diagnosis of active pulmonary TB in children. Application of nested PCR assay could be used as a follow-up tool in monitoring of pulmonary tuberculosis in children. Regarding HLA antigens the results showed high frequency of the previously mentioned HLA antigens with pulmonary TB which may indicate increased susceptibility to pulmonary TB infection and on other hand high frequency of other mentioned HLA antigens among controls may indicate a protective effect of these antigens. Anyhow further studies are still needed to be done and on a wide scale to prove the association of HLA antigens and tuberculosis