Study of gonadal hormones in Egyptian female children with sickle cell anemia in correlation with iron overload: single center study

Objective/Background: Sickle cell disease is a hereditary hemoglobinopathy characterized by abnormal hemoglobin production, hemolytic anemia, and intermittent occlusion of small blood vessels, leading to tissue ischemia, chronic organ damage, and organ dysfunction including endocrine organs. The aim of this work was to evaluate some gonadal hormones in female children with sickle cell anemia [SCA] in correlation with iron overload

Methods: This study was conducted on 40 female children with SCA with a serum ferritin of > 1000 ng/mL, who were attendants at the Hematology Unit, Pediatric Department, Tanta University, Tanta, Egypt in the period from May 2012 to April 2014. Their ages ranged from 11 years to 15 years and the mean age value was 12.63 +/- 1.36 years [Group I]. Forty female children with SCA of matched age with no iron overload served as a control Group [Group II]. For all patients in Groups I and II the following were performed/assessed: complete blood count, hemoglobin electrophoresis, serum iron status, serum estrogen, luteinizing hormone [LH], and follicle-stimulating hormone [FSH]

Results: There were significantly higher serum ferritin and serum iron levels and significantly lower total iron binding capacity, FSH, LH, and estrogen levels in Group I compared with Group II [mean serum ferritin was 2635.1 +/- 918.9 in Group I vs. 292.55 +/- 107.2 in Group II with a p value of .001; mean serum iron was 196.3 +/- 55.6 in Group I vs. 120 +/- 16.57 in Group II with a p value of .001 and mean serum total iron binding capacity was 247.3 +/- 28.6 in Group I vs 327.8.7 +/- 21.96 in Group II with a p value of .001; mean FSH level was 1.36 +/- 0.22 mIU/mL in Group I vs. 2.64 +/- 0.81 mIU/mL in Group II with a p value of .021; mean LH level was 0.11 +/- 0.006 mIU/mL in Group I vs. 1.78 +/- 1.12 mIU/mL in Group II with a p value of .003; mean estrogen level was 21.45 +/- 10.23 pg/mL in Group I vs. 42.36 +/- 15.44 pg/mL in Group II with a p value of 0.001] with significant negative correlation between serum gonadal hormones and serum ferritin [r = 0.835 and p value of .01 for FSH and serum ferritin; r = 0.597 and a p value of .01 for LH and serum ferritin; and r = 0.624 and p value of .01 for estrogen and serum ferritin

Conclusion: Female patients with SCA with iron overload may have gonadal hormone deficiency with significant negative correlations between gonadal hormones including FSH, LH, estrogen, and serum ferritin. Recommendations include regular iron chelation for prevention of irreversible damage of the ovaries and attaining normal sexual maturation, and regular follow up for females with SCA with assessment of puberty as they are more vulnerable to develop hypogonadism and may require hormonal replacement therapy

Frequency of 11 q23/MLL gene rearrangement in Egyptian childhood acute myeloblastic leukemia: biologic and prognostic significance

Molecular cytogenetic abnormalities involving 11q23 are among the most cytogenetic abnormalities in AML patients. We aimed to evaluate the frequency of MLUAF9 fusion gene in AML patients and its prognostic significance. Twenty eight children patients with AML and twenty healthy controls were subjected to complete clinical examination and laboratory investigations including, complete hemogram and BM examination. Diagnosis was. based on FAB morphologic and immunophenotypic criteria. Detection of [MLUAF9] fusion gene were assessed by dual color FISH. Follow up were carried out clinically and by blast count in BM, and response to therapy to detect the outcome of the disease. The frequency of MLL fusion gene MLUAF9 in AML cases was 21% [6/28]. Four patients with MLUAF9 fusion gene were newly diagnosed, two cases were at relapse and no patient at remission showed positivity. As regard the clinical outcome, five out of six MLL positive cases died, three of them during induction and two during relapse. The FAB AML subtypes with MLUAF9 fusion were one M2, three M4 and two M5. FISH technique is a sensitive tool for rapid detection of MLL gene rearrangement at diagnosis which is of high clinical relevance directing treatment strategy as most of these abnormalities have been associated with poor prognosis

Prognostic value of plasma pro-adrenomedullin and antithrombin levels in neonatal sepsis

Neonatal sepsis is one of the major causes of morbidity and mortality in neonates. Proper diagnosis and management of neonatal septicemia can markedly affect prognosis of neonatal sepsis. In sepsis serum pro-Adrenomedullin level [pro-ADM] was known to be increased while Anti thrombin is rapidly depleted as a result of decreased synthesis, increased destruction, and enhanced clearance. The aim of this study was to clarify the prognostic value of serum Pro-ADM and Anti thrombin level in neonatal sepsis. 40 full term neonates with sepsis were enrolled in this study including 20 cases with mild sepsis and 20 cases with severe sepsis. They were admitted to the neonatal intensive care unit, they included 26 males and 14 females with a mean birth weight of 3.2 +/- 0.26 kg. Twenty healthy full term neonates of matched age and sex served as a control group. Serum levels of Pro ADM and Antithrombin were measured in all patients and control group. Serum Pro ADM level was significantly higher in neonates with sepsis than control group, was significantly higher in severe than mild sepsis and was significantly higher in the unsurvived cases. Antithrombin concentrations were significantly lower in neonates with sepsis than control group, significantly lower in severe than mild sepsis and significantly lower in neonates with sepsis who died than who survived. In conclusion, higher pro-ADM and lower initial AT levels in neonatal sepsis are associated with severe disease and increased risk of mortality

Antioxidant enzymes and ceruloplasmin plasma levels in children with autism

Autism is a behaviorally defined neuron-developmental disorder usually diagnosed in early childhood that is characterized by impairment in reciprocal communication and speech, repetitive behaviors, and social withdrawal Although both genetic and environmental factors are thought to be involved, none have been reproducibly identified. Oxidative stress has been implicated in the pathogenesis of diverse disease states, and may be a common pathogenic mechanism underlying many major psychiatric disorders as autism. Levels of the major antioxidant serum proteins, namely Glutathione peroxidase, Superoxide Dismutase and ceruloplasmin, are decreased in children with autism. The aim of this study: was to evaluate the plasma levels of the major antioxidant enzymes include. Superoxide Dismutase [SOD], Glutathione Peroxidase [GSH-Px] and Ceruloplasmin in children with autism, compare them with normal control children and to correlate between the plasma levels of these major antioxidant and the severity of autism .This study was carried out in The Psychiatry Unit, Department of Pediatrics, Tanta University Hospital. Thirty children with prior diagnosis of autism[24 males, 6 females] were included in the study, their age range was[3-9 years] with the mean age was [5 +/- 1.8 years]. The intial Childhood Autism Rating Scale [CARS] score for these children was >/= 30. Children with a CARS score >/= 30 were considered to have autism. Intial CARS score range for chidren with autism was [31-60]. The control group consisted of thirty healthy children [10 females, 20 males]. Their age range was [2-10 years] and the mean age was 5.3 +/- 2.4 years. The plasma levels of the major antioxidant, Glutathione Peroxidase, Superoxide Dismutase and Ceruloplasmin In children with autism, were significantly lower than the plasma levels of these antioxidants in the control children [P<0.01]. Also there was a significant inverse correlation between the plasma levels of this major antioxidant and the severity of autism according to CARS score. These data revealed that, antioxidants defense mechanisms might be impaired in children with autism, understanding these basic pathologic processes may yield novel target for the development of more effective treatment for autism

Diagnostic value of umbilical cord blood procalcitonin level as an early marker of neonatal sepsis

Septicemia is a systemic disease associated with the presence and persistence of bacteria and their toxins in the blood. It is one of the major causes of morbidity and mortality in the neonatal period. Early diagnosis and proper manag-ement of neonatal septicemia can bring down the morbidity and mortality rates. Procalcitonin [PCT] has recently become of interest and proposed as a possible marker of the systemic inflammatory response to infection in critically ill patients. The aim of this study was to clarify the diagnostic value of serum Procalcitonin [PCT] level as an early marker for diagnosis of neonatal sepsis. Twenty neonates with maternal risk factors for sepsis were included in this study. They included 8 males, 12 females with a mean gestational age of 38.2 +/- 1.76 weeks and mean birth weight of 3.25 +/- 0.34 kg. Twenty healthy children of matched age and sex with no maternal risk factors for sepsis were included in the study as a control group. Serum PCT concentrations were measured at umbilical cord blood samples, taken at time of delivery and peripheral blood samples taken 48 hours later using an immunochromatographic semi quantitative test [PCT-Q; Brahms, Hennigsdorf, Germany] and C- reactive protein [CRP] concentration was measured using an immune-oreactive quantitative method. Serum PCT concentrations were significantly higher in neonates with confirmed sepsis than both control group and neonates with clinically suspected but not confirmed sepsis. PCT is a more sensitive and specific early marker of neonatal sepsis compared with other laboratory parameters of sepsis

Serum leptin level among malnourished children with and without pneumonia

Protein-energy malnutrition [PEM] is a significant problem among paediatric population, the most severe forms of PEM were marasmus and kwashiorkor. Infectious complications are important cause of death among children with PEM. PEM is a common cause of secondary immune deficiency and susceptibility to infection in humans. Malnutrition impairs the immunity through a variety of mechanisms. The aim of this study is to evaluate the serum leptin level in children with PEM with and without pneumonia. 60 children were included in the study; 20 were used as a control, 20 child had PEM with out infection and 20 child had PEM associated with pneumonia. All included children were subjected to nutritional assessments. Haematological tests [haemoglobin concentration, white blood cell [WBC] count and differentials including CD4 count and ratio, serum albumin, blood glucose, white blood cell count, urine nitrogen, and serum ferritin], and chest x-ray reports were done. The serum leptin level and CD4 ratio were significantly lower in both groups with PEM when compared to the control group [p < 0.001]. Also, serum leptin level and CD4 ratio were significantly lower in the groups with PEM and pneumonia one compared to the group with PEM without pneumonia [p<0.001]. The leptin hormone has an important role in immune system and its deficiency in PEM together with reduction of CD4 ratio are important factors for contracting infections

role of hepcidin level in iron overload in children with beta-thalassemia

Thalassemias are a group of inherited blood disorders with defective production of hemoglobin. Patients with beta-thalassemia develop iron overload due to increased iron absorption and transfusion therapy. Hepcidin is a hepatic hormone released in case of iron overload to regulate systemic iron homeostasis by inhibiting iron absorption from diet and recycling of iron by macrophages. To determine role of hepcidin in the pathogenesis of iron overload in 6-thalassemia. 20 Patients with beta thalassemia major [TM] included 10 males and 10 females, 20 patients with beta thalassemia intermedia [TI] included 10 males and 10 females and twenty healthy children of matched age and sex were included in this study. We assessed iron overload by measuring serum ferritin, assessed erythropoietic activity by measuring serum erythropoietin levels, and correlated these with urinary hepcidin measurements. We found severe urinary hepcidin deficiency in TI with strong inverse relationship between urinary hepcidin and serum erythropoietin levels in comparison with control group. In contrast, urinary hepcidin levels were elevated in TM with decrease of erythropoietin levels. In addition, serum ferritin level was significantly higher in TM than TI and significantly higher in TM and TI compared with normal control. Hepcidin deficiency may be the key factor allowing excessive iron absorption and iron overload in TI while in TM, chronic hemolysis and frequent blood transfusions may be the main factors that increase iron load

lnterleukin-1 beta, lnterleukin-1 receptor antagonist and tumor necrosis factor-alpha, in children with simple febrile convulsions

Pro- and anti inflammatory cytokines regulate the febrile response during infection. Febrile convulsions [FCs] conversely are associated with rapid onset of high fever. Activation of the cytokine network has been shown in previous studies of FCs and cytokines. In this study, the association between cytokines and FCs was further investigated. lnterleukin-1 beta [IL-1 beta], interleukin-1 receptor antagonist [IL-1RA], and tumor necrosis factor-a [TNF-a] plasma levels were measured with enzyme-linked immunosorbent assay in 40 children with FCs and in 20 age-matched febrile controls immediately on arrival at the emergency room or pediatric clinic. Cerebrospinal fluid [C.S.F.] level of these cytokines also, was measured in 7 FC children. The plasma IL-1 beta level was lower in FC children when compared with controls [mean +/- SD, 19.5 +/- 7.72 pg/ml vs. 57.2 +/- 10.43 pg/ml; p = 0.1], but the difference was not statistically significant. FC patients had significantly higher plasma IL-1RA levels [mean +/- SD, 15357 +/- 4870 pg/ml vs. 3963 +/- 2950 pg/ml; p = 0.0005]. The plasma IL-1RA/IL-1p ratio was significantly higher in FC patients compared with controls [mean, 7875 vs. 69.283; p < 0.0001]. There was no significant difference in plasma TNF-alpha level between FC patients and controls [mean +/- SD, 7.42 +/- 3.12 pg/ml vs. 6.71 +/- 4.8; p = 0.63]. In C.S.F, IL-1RA was detectable in 5, IL-1beta in one and TNF-alpha was undetectable in the 7 studied FC patients. Logistic regression analysis was used to find the most significant predisposing factors for FCs. In this analysis, the high plasma IL-1RA/IL-1beta ratio was the most significant factor connected to FCs [OR, 41.5; 95% CI, 4.9-352.8]. Present results support the hypothesis that the cytokine network is activated and could have a role in the pathogenesis of FCs

Prognostic value of serum S100 protein level in newborn infants with hypoxic ischemic encephalopathy

Hypoxic ischemic encephalopathy [HIE] is the most common cause of neurologic disease during neonatel period and is associated with high mortality and morbidity rate including cerebral palsy, mental retardation and seizures. S100 beta[2] is normally present in serum in very low concentrations, but found in high concentrations in the brain both in glial cells and in neurons. Serum S100 protein peaked in the first day after birth in asphyxiated newborn infants. The aim of this study was to clarify the prognostic value of serum S100 protein level as a marker of cerebral injury in newborn infants with birth asphyxia [HIE]. 20 newborns with HIE were investigated successively in the first 3 days after birth in comparison with 20 healthy newborn infants as a control group. S100 protein levels were detected by a monoclonal two-site immuno-luminometric assay. Follow up of the cases for 6 months after discharge from incubators was done to detect cases that developed cerebral palsy. We found significant increase in serum S100 protein level in newborn infants with birth asphyxia as compared to control group, also we found significant positive correlation between day 1 S100 protein levels and severity of HIE and positive correlation between day 1 S100 protein levels and future development of cerebral palsy. Early determination of serum S100 protein in first day after birth in newborn infants with hypoxic ischemic encephalopathy may be used as a good marker for assessment of severity of HIE and extent of brain damage and to predict the possibility of future development of cerebral palsy in newborn infants with HIE

Circulating Thrombopoietin and Interleukin-11 in Thrombocytopenic Neonates with Sepsis

Thrombocytopenia is a commonly encountered hematological complication in neonates with sepsis. Thrombopoietin [TPO] is the major regulator of the platelet production in neonates. It is unique among the haematopoietic cytokines for maintenance of the most primitive haematopoietic stem cells. Interleukin-11[lL-11] stimulates megakaryorytopoiesis and platelet production. The aim of this study was to determine the variation in the TPQ and IL-11 levels and/or if they would correlate with platelet count or not in infected neonates with sepsis. Thirty five neonates with sepsis admitted to the Intensive Care Unit, Pediatric Department, Tanta University Hospital, were enrolled in this study. Twenty healthy neonates sewed as a control group. All these neonates were subjected to the following: Complete blood count [CBC], blood culture, C-reactive protein [CRP], chest X-ray, coagulation studies including prothrombin time, partial thromboplastin time, fibrinogen and D-dimer. Plasma TPO and IL-11 levels were performed using Enzyme-Linked lmmunosorbent Assay[ELISA], The results showed that sick neonates with sepsis had significantly higher plasma levels of both TPO and IL-11 [P<0. 05]. Also, there was significant inverse correlations between the platelet count and TPO and IL-11 levels [r=-0.917 and-0.908 respectively, P value<0.01]. TPO and IL-11 are significantly increased in neonatal sepsis with thrombocytopenia and they are being explored as potential therapeutic agents in these patients