Some predisposing factors for stroke in children with sickle cell anemia

This study was done to detect cases of silent and clinically overt strokes in children with sickle cell anemia [SCA] either in the steady or thrombotic crisis states as well as to evaluate the role of some laboratory and genetic parameters as predisposing factors for development of stroke including: fibrin peptide-A [FPA], thrombinantithrombin 111 complex [TAT], fibrin degradation products [D dimer], platelet endothelial cell adhesion molecule-l [PECAM-1] and molecular genetic study of the angiotensin converting enzyme [ACE] gene polymorphism. The study included 20 children with SCA diagnosed clinically, hematologically and confirmed by hemoglobin electrophoresis. They were divided into two groups, group I; included 10 children with SCA in steady state and group PI; included 10 SCA children in thrombotic crisis. Another 10 healthy children with matched age and sex were taken as a control group. All the studied groups were subjected to full clinical examination, measurements of: FPA, TAT, D-dimer and PECAM-1 as well as molecular genetic study of the ACE gene polymorphism. Brain computed axial tomography [CT] scan and/or magnetic resonance imaging [MRI] as well as electro-encephalographic studies [EEG] were done only for patient groups. Results showed that silent ischemic brain infarction evidenced only by CT scan and/or MRI was present in one patient in group I [10%] and one patient in group II [10%]. On the other hand, two patients in group II [20%] were presented by clinically overt strokes. Thus, according to the presence or absence of stroke either silent or clinically overt there were stroke group [4 children] and non-stroke group [16 children]. Laboratory results showed that the levels of FPA, TAT, D-dimer and PECAM-1 were significantly elevated in SCA patients both in the steady and crisis states as compared to control, with more evident significant elevation in group I1 [thrombotic crisis] as compared to group I [steady state]. Stroke group showed significant elevation in all the studied parameters; FPA, TAT, D-dimer and PECAM-1 as compared with non-stroke group. The molecular study results showed that the frequencies of both DD genotype and D allele of ACE gene in the thrombotic crisis were significantly higher than in the control group and that all stroke group children are of DD genotype. In conclusion; significant increase in FPA, TAT, D-dimer and PECAM-1 levels as well as the presence of ACE D allele of the ACE gene are significant predisposing factors for stroke in children with SCA either in the steady or in the crisis states which may recommend regular follow-up by thorough neurological examination and neuro-imaging studies for early detection of silent brain infarction as well as the preventive use of effective therapies as repeated blood transfusion and bone marrow transplantation

Study of some early diagnostic predictors and role of antioxidant therapy in neonatal sepsis

This study was conducted to estimate the sensitivity and specificity of some early diagnostic predictors of neonatal sepsis including: inflammatory cytokines [interleukin-6 [IL-6], tumor necrosis factor alpha [TNF-alpha]], enzymatic antioxidants [glutathione peroxidase [GPX], superoxide dismutase [SOD]], non enzymatic antioxidants [uric acid [UA], albumin [ALB]] and markers of oxidative stress [nitric oxide [NO], creatine phosphokinase [CPK], malondialdehide [MAD]] as well as to evaluate the role of oral administration of vitamin A and / or vitamin C as adjuvant line of therapy. This study was done on 60 septic full term neonates who were admitted to Neonatal Intensive Care Unit [NICU], Tanta University Hospital. Another 15 healthy neonates with matched age and sex served as a control group. The septic neonates were classified randomly into 4 equal groups according to the type of therapy; Group I received antibiotics as a sole line of therapy, Group II received antibiotics and oral vitamin A [5000 IU every other day], Group III received antibiotics and oral vitamin C [100 mg / kg], and Group IV received antibiotics and both oral vitamins A and C. All neonates were subjected to thorough clinical examination, sepsis work up as well as estimation of: IL-6, TNF-alpha, GPX, SOD, UA, ALB, NO, CPK and MDA. Follow up for 2 weeks was done when a second blood sample was taken for the same laboratory investigations. Bacterial cultures revealed that the most common pathogen was Klebsiella [37%] and the most sensitive antibiotic was Imipenem [++++], The sensitivity and specificity of IL-6 and SOD were 100% followed by NO and CPK [100% sensitivity and 93.33% specificity]. Before therapy, there were significant increases in IL-6, TNF-alpha, GPX, SOD, NO, CPK, MDA and significant decreases in ALB and UA in septic neonates as compared with the control group. After therapy, significant decreases in inflammatory cytokines, enzymatic antioxidants and markers of oxidative stress were found in all the septic groups but evidently more in group IV, followed by group II

Conclusion: IL-6 and SOD are advised as the best predictors for early diagnosis of neonatal sepsis followed by NO and CPK. Oral administration of vitamin C adds mostly no benefit more than the sole administration of antibiotics. On the other hand, the combined administration of both vitamins A and C acts in synergism better than the sole administration of vitamin A and can be recommended as an additional line of therapy in neonatal sepsis that can decrease the membrane lipid per oxidation and the risk of free radical damage

Susceptibility for stroke in children with sickle cell anemia

This study was done to detect cases of silent and clinically overt strokes in children with sickle cell anemia [SCA] either in the steady or thrombotic crisis states as wed as to evaluate the role of some laboratory and genetic parameters as predisposing factors for development of stroke including: fibrin peptide-A [FPA], thrombin-antithrombin Ill complex [TAT], fibrin degradation products [D-dimer], platelet endothelial cell adhesion molecule-I [PECAM-1] and molecular genetic study of the angiotensin converting enzyme [ACE] gene polymorphism. The study included 20 children with SCA diagnosed clinically, hematologically and confirmed by hemoglobin electrophoresis. They were divided in to: group I; included 10 children with SCA in the steady state and group II; included 10 SCA children in thrombotic crisis. Another 10 healthy children with matched age and sex were taken as a control group. A!! the studied groups were subjected to full clinical examination, measurements of: FPA, TAT, D-dimer and PECAM-1 as we1 as molecular genetic study of the ACE gene polymorphism. Brain computed axial tomography [CT] scan and/or magnetic resonance imaging [MRI] as well as electroencephalographic studies [EEG] were done only for patient groups. Results showed that silent ischemic brain infarction evidenced only by CT scan and/or MRI was present in one patient in-group I [10%] and one patient in-group II [10%]. On the other hand, two patients in-group II [20%] were presented by clinically overt strokes. Thus, according to the presence or absence of stroke [either silent or clinically overt] there were stroke group [4 children] and non-stroke group [16 children]. Laboratory results showed that the levels of FPA, TAT, D-dimer and PECAM-1 were significantly elevated in SCA patients both in the steady and crisis states as compared to control, with more evident significant elevation in group II [thrombotic crisis] as compared to group I [steady state], Stroke group showed significant elevation in all the studied parameters; FPA, TAT, D-dimer and PECAM-I as compared with non-stroke group. The molecular study results showed that the frequencies of both DD genotype and D allele of ACE gene in the thrombotic crisis were significantly higher than in the control group and that all stroke group children are of DD genotype. In conclusion; significant increase in FPA, TAT, D- dimer and PECAM-1 levels as well as the presence of ACE D allele o! the ACE gene are significant predisposing factors for stroke in children with SCA either in the steady or in the crisis states which my recommend regular follow-up by thorough neurological examination and neuro-imaging studies for early detection of silent brain infarction as well as the preventive use of effective therapies as repeated bloi3d transfusion and bone marrow transplantation

Early detection of doxorubicin-induced cardiotoxicity in children with hematological malignancies

This study aimed to investigate the value of conventional Doppler-echocardiography, Doppler tissue imaging [DTI], and serum cardiac troponin I [cTni] as early predictors of cardiotoxicity in children treated with doxorubicin for different hematological malignancies and to evaluate their feasibility as early screening tests in assessing the left as well as the right ventricular systolic and diastolic functions. This study included 19 clinically asymptomatic children aged 4.9 +/- 2.1 years with normal systolic function who were receiving doxorubicin chemotherapy [cumulative dose= 122.4 +/- 59.9 mg/m2] for different malignant neoplasms [16 children having acute lymphoblastic leukemia, 2 having acute myeloid leukemia and I having leukemic phase of lymphoma]. They were subjected to Doppler-echocardiographic and DTI examination of the right ventricular [RV] and left ventricular [LV] systolic and diastolic functions as well as estimation of serum levels of cTni by sandwich immunoassay after the last dose of doxorubicin during the induction-remission therapy. Another 20 healthy normal children were taken as a control group. Results showed that the LV systolic functions as well as LV and RV diastolic functions [assessed by Doppler study of mitral and tricuspid inflow, and mitral flow propagation velocity [MPW and myocardial performance index [MPI] were impaired in patients compared with controls. DTI study confirmed and disclosed such impairment in LV and RV systolic [decreased lateral mitral and tricuspid annulus systolic [Sa] velocities] and diastolic functions [decreased early diastolic tricuspid and lateral and septal mitral annulus [Ea] velocities and mitral Ea/Aa] in patients compared with controls. Serum cTni was statistically significantly increased in-patient as compared with the control group. There was a significant negative correlation between serum levels of cTni and Ea/Aa. On the other-hand, cumulative dose of doxorubicin was not correlated with either serum cTni or any systolic or diastolic cardiac functions

Conclusion: DTI confirmed and disclosed abnormal RV and LV systolic and diastolic functions reported by conventional Doppler-echocardiography in asymptomatic doxorubicin-treated children. DTI had more ability to detect abnormal RV and LV systolic and diastolic functions than conventional Doppler-echocardiography. Serum cTni, which is considered as a marker for myocardial cell injury significantly, correlates with the degree of diastolic dysfunction detected only by DTI [Ea/Aa]. The repetitive measurements of the new DTI-derived velocities, Doppler-derived indices [MPI], M-mode- derived MPV and serum cTni could add significant value in the early defection of doxorubicin-induced cardiotoxicity and enhance several studies to find suitable cardio protective free radical scavengers which can reduce the cardio toxic effects of doxorubicin including; dexrazoxane, exogenous melatonin, phosphodiesterase inhibitors type 4 or induction of metallothionein by zinc

Early predictors of neurodevelopmental outcome in neonatal bacterial meningitis

Neonatal bacterial meningitis [NBM] constitutes a major challenge for the increasing incidence and adverse outcome despite new tools in diagnosis and treatment. Neurodevelopment outcomes are the most severe and have to be predicted as early as possible in the course of the disease. This work aimed to study the contribution of some clinical, laboratory, electroencephalographic and ultrasonic procedures for predicting adverse outcomes of NBM, early in the course of the disease. This study included 45 full term newborn infants who were admitted to Neonatal Intensive Care Unit [NICU], Tanta University Hospital, with definitive NBM proved by cerebrospinal fluid [CSF] culture. All patients were subjected to thorough history taking, clinical examination, electroencephalography [EEG], cranial ultrasound Doppler as well as laboratory investigations including; blood culture, CSF culture, total leukocyte count, platelet count, plasma lactate, CSF lactate and CSF glutamate. All these procedures were fulfilled during the first week sf admission. Some cases were re-evaluated for EEG and cranial Doppler. Cases were followed for neurodevelopmental outcome for one year after discharge. The results showed adverse outcomes of cases of NBM at one year age. They revealed blindness, hemiparesis, microcephaly, cerebral palsy [8% for each one], seizures disorders [12%], hearing loss [16%] hydrocephalus [20%] and death [20%]. The most important clinical and laboratory predictors of adverse outcome were the presence of seizures duration > I2 hours [sensitivity 8804 and specificity 85%], coma at presentation [sensitivity 40% and specificity 95%], need for ventilator support [sensitivity 12% and specificity 95%], total leukocyte count <5000/ mm3 [sensitivity 36% and specificity 90%] and platelet count <10[5]/mm3 [sensitivity 40% and specificity 90%]. EEG results showed that EEG background activity and overall EEG description were identified as sensitive predictors of adverse outcome [sensitivity 88% and specificity 90%]. Elevated CSF lactate and glutamate were recorded to be sensitive predictors of adverse outcome [sensitivity 80% and specificity 95%]. Elevated plasma lactate recorded 60% sensitivity and 70%specificity as a predictor of outcome in NBM. Cranial Doppler was also proved a sensitive outcome predictor especially decreased regional cerebral blood flow [sensitivity 72% and specificity 90%] and increased pulsatility indices [sensitivity 80% and specificity 95%]

Conclusion: increased CSF levels of lactate and glutamate as well as presence of high pulsatility index by cranial ultrasonography provided the most useful information as early outcome predictors in NBM. EEG background activity and presence of seizures more than 12 hours came in the second degree in predicting adverse outcome. Interpretation of these sensitive clinical, laboratories, electroencephalographic and ultra-sonographic parameters may help in early prediction of the adverse neurodevelopmental outcome in NBM and may be of benefit in the rapid intervention and management of these cases especially in high-risk groups

Study of serum insulin-like growth factor-I, prealbumin and procollagen type III peptide in children with protein energy malnutrition

This study was done to estimate the value of determination of serum concentrations of albumin, prealbumin, insulin-like growth factor-I [IGF-I] and procollagen 111 peptide [PIIINP] as early predictors of protein energy malnutrition [PEM] in children as well as to demonstrate the effect of nutritional rehabilitation therapy on these parameters. This work was carried out on 60 infants and children suffering from PEM. Their age ranged from 6 months to 3 years. They were classified into four groups according to Welcome classification of PEM; group I included 15 underweight infants and children, group I/ included 15 infants and children with marasmus, group III included 15 infants and children with kwashiorkor and group IV included 15 infants and children with marasmus-kwashiorkor. Another 30 normal healthy infants and children of matching age and sex served as a control group. All patients and control groups were subjected to a careful history taking, thorough clinical examination, anthropometric measurements including; weight, length, head circumference, mid-upper arm circumference [MUAC] and skin fold thickness [SFT] as well as laboratory investigations including complete blood picture, serum albumin, serum prealbumin, serum IGF-I, and serum PIIINP. All these laboratory investigations were repeated after 6 weeks of nutritional rehabilitation therapy in the form of a diet providing 4 gm proteins/kg/day and 150 cal./kg/day

Before nutritional rehabilitation: weight, MUAC and SFT were significantly decreased in comparing all the studied PEM groups and control one with a significant decrease in length and head circumference only in marasmus and marasmus-kwashiorkor groups. Albumin, prealbumin, IGF-I and PlllNP were significantly low in all the studied PEM groups compared to control one with more significant decrease in kwashiorkor group. Correlation study using weight for age percentage of median [WAM] as a fixed parameter showed a highly significant correlation with IGF-I more than with PlllNP and prealbumin

After nutritional rehabilitation: weight, MUAC and SFT were significantly increased in PEM groups as compared to that before nutritional rehabilitation. Albumin, prealbumin, IGF-I and PlllNP were significantly increased in PEM groups as compared with their values before nutritional rehabilitation. Correlation study using WAM as a fixed parameter showed a highly significant correlation with PlllNP more than with IGF-I and prealbumin

Conclusion: IGF-I is an early sensitive predictor of malnutrition status before nutritional rehabilitation therapy as compared to albumin, prealbumin and PIIINP. On the other-hand, PlllNP can be used as a sensitive prognostic marker that evaluates the short-term response to nutritional rehabilitation in malnourished children more than other nutritional parameters

Risk factors for development of peripheral neuropathy in type I diabetes mellitus

This study was done to investigate the role of some risk factors for development of peripheral neuropathy in children and young adolescents with type I diabetes mellitus [type I DM]. Diabetic patients were divided into three groups: Group I included 10 diabetic patients with clinically and electrophysiologically evident peripheral neuropathy. Group II included 20 diabetic patients with subcIinicaI peripheral neuropathy evident only by measuring the motor nerve conduction velocity [MCV], and Group III included 30 diabetic patients with neither clinical nor subclinical peripheral neuropathy. The patients included were 33 females and 27 males, their age ranged from 5-20 years. Ten normal healthy individuals of matched age and sex served as a control group [Group IV]. All the studied groups were subjected to full clinical and neurological examination, measuring [MCV] of the common peroneaI and median nerves, estimation of egcosyIated hemoglobin level [HbA1c], assay of erythrocyte superoxide dismutase [SOD] as well as molecular genetic study of the manganese superoxide dismutase [MnSOD] gene polymorphism. Our results showed a significant increase in HbA1c level and a significant decrease' In SOD level as well as MCV of common peroneaI and median nerves in group I and group II as compared with group III and group IV. There were significant negative correlations between HbA1c when compared with SOD and MCV as well as signiticant positive correlations between SOD levels and MCV in all the diabetic groups. The frequencies of Ala allele and the AIa/Ala genotype of the Mn-SOD gene were significantly lower in neuropathic diabetic patients. In contrast, the Val allele and VaWaI genotype were significantly more frequent in neuropathic diabetic patients than in diabetic subjects without peripheral neuropathy

Conclusion: EIectrophysioIogicaI studies should be done in all type-I diabetic patients regardless their age or duration of the disease for early diagnosis and following the progression of diabetic neuropathy before start of clinical manifestations [subcIinicaI peripheral neuropathy]. Poor glycemic control, low levels of the key antioxidant enzyme SOD, and the Val allele with Ala/ VaI genotype of the Mn-SOD gene Were signiticant risk factors for the development of diabetic neuropathy in type 1 diabetic patients which may necessitate appropriate support for enhancing antioxidant supply to act against the rapid onset and progression of diabetic neuropathy, by reducing the excess of oxygen free radicals [OFR] and peroxide

Serum levels of soluble Fas in children with congestive heart failure

This study was done to investigate the role of apoptosis [programmed cell death] in children with congestive heart failure [CHF]. Serum levels of soluble Fas [sFas], an inhibitor of apoptosis was estimated in 30 children with CHF, 10 due to rheumatic heart disease [RHD], 10 due to congenital ventricular septal defect [VSD] and 10 due to idiopathic dilated cardiomyopathy [IDCM]. The children included were 20 males and 10 females, aged between 7 to 14 years. The diagnosis was based on thorough clinical and echo-Doppler examinations. They were classified according to the New York Heart Association [NYHA] functional class based on their clinical characteristics. Ten normal healthy children with matched age and sex served as a control group. Our results showed that there was a significant increase in serum levels of sFas in children with CHF as compared to the control group. There was a significant positive correlation between serum levels of sFas and NYHA functional class. Serum levels of sFas were correlated with certain echo-Doppler parameters that reflect the severity of CHF resulting in a significant positive correlation with pulmonary wedge pressure [PWP] and a significant negative correlation with ejection fraction [EF]. The increase in serum levels of sFas was related to the severity of CHF independently of the underlying cardiac disease. Serum levels of sFas tended to decrease significantly in children with CHF who underwent clinical improvement but not significantly changed in the stable cases during the six months follow up. There was no significant difference in serum levels of sFas between the survivors and those children who died. In conclusion: serum levels of sFas, an inhibitor of apoptosis may play an important role in the pathophysiologic mechanisms of CHF in children