prognostic value of autotaxin activity and gene expression, matrix metalloproteinase-9 and p 53 antibodies in breast cancer patients

The aim of this study was to analyze changes in autotoxin [ATX] [both enzyme activity and gene expression], metalloproteinase-9 [MMP-9] and p53 antibodies [Abs] serum levels in breast cancer patients and to correlate their results with various clinical, pathological features of breast cancer. Sixty female breast cancer patients [42 with lymph node [LN] metastasis and 18 without LN metastasis] were included in this study and subjected to determination of ATX [both activity by colorimetric method and gene expression by RT-PCR] and both p53 Abs and MMP-9 by ELISA technique. Our results showed that there were statistically significant differences between breast cancer patients with and without LN metastasis in all the studied parameters except for p53 Abs. ATX [both activity and gene expression] and the serum levels of both MMP-9 and p53 Abs, were significantly different between different stages and grades of breast cancer patients with increasing activity and levels from stage I to IV and from grade I to III. Only ATX [both activity and expression] was significantly different between patients with tumor size less than or more than 5. There was a highly significant correlation between ATX activity and gene expression. The present study suggested that ATX activity, MMP-9 and p53Abs could serve as useful and convenient prognostic and detection markers of metastasizing breast cancer. Also, ATX activity may be used as an index for increased ATX gene expression

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

Steroid sparing using safer drugs in the management of children and adolescents with chronic asthma

This study included forty five [19 males and 26 females] children and adolescent patients [mean age 11.2 +/- 3.4 years] suffering from chronic bronchial asthma, in whom oral and/or inhaled steroids were necessaary to control their symptoms. They were selected from patients attending outpatient clinics of Pediatrics and Chest Departments of Tanta University Hospital. They were assigned randomly into 3 treatment groups [15 cases each]; Lidocaine group receiving nebulized lidocaine 1 mg/kg/dose twice daily, Montelukast group receiving oral montelukast 5 mg once daily, and control group who continued on their traditional drugs [bronchodilators and steroids]. History and clinical examination were performed and the following investigations were done to all study cases as a base line and after 2 weeks of treatment: PEFR, FEV1, FEF[25.75%], Induced sputum was collected and utilized to do sputum eosinophil count, sputum eosinophilic cationic protein [ECP] and sputum nitric oxide [NO] metabolites [nitrites and nitrates]. PEFR increased significantly 20 minutes after lidocaine inhatation, indicating bronchodilating effect of lidocaine. Studied pulmonary function parameters [PEFR, FEV1 and FEF[25-75%], significantly increased, while induced sputum analysis data [sputum eosinophil count % and sputum ECP] significantly decreased after treatment in Iidocaine and montelukast groups as compared to base line values and control group. However, the difference between the two groups after treatment was not significant. Sputum total nitriteslnitrafes did not change significantly after treatment in both groups and in controls due to pretreatment of ail study cases with steroids. Successful steroid withdrawal was obtained in 86% of lidocaine group and 73% of montelukast group along of 2 weeks. The difference between success rates in the two groups was statistically insignificant [p0.05]

Conclusion: the present study suggests that both nebulized lidocaine and oral montelukast could be reasonable steroid sparing agents allowing maintained asthma control with no or reduced dose of steroids. Lidocaine is cheap while montelukast is easily administered in children. Both agents exhibited comparable steroid sparing actions without significant side effects. However, lidocaine inhalation works as asthma reliever as well, due to its bronchodilating action

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

Immune response in children with idiopathic generalized epilepsy and those with autistic spectrum disorders

There is new evidence that epilepsy and autism may be accompanied by abnormalities in the inflammatory response system [IRS]. Products of the IRS such as pro inflammatory cytokines may induce some of behavioral symptoms of epilepsy and autism such as social withdrawal and sleep disturbances. Also, these cytokines are supposed in the etiopathogenesis and associates of these neurobehavioral disease entities. The main aim of this study was to examine whether epilepsy or autism are associated with activation of the IRS. We measured the serum concentrations of interleukins 6, 10, tumor necrosis factor-alpha and interferon gamma. Abo we measured serum levels of immunoglobulins G, A, M. The results of our study showed significantly increased production of interferon gamma [INF-y] and a trend forward a significantly increased production of IL-6 and TNF-alpha by whole blood of autistic children. There was no significant difference in the serum concentration of IL-6 and that is a trend toward a significant increase in the production of IL-10 and TNF-y autism but not in epilepsy. No significant change in the production of IL-10 in both patients groups as compared to controls. In our study there were decreased levels of immunoglobins M, A and 6 in epileptic and autistic children as compared to control. ANOVA showed more decrease in autistic children

Conclusion: epilepsy and autism may be a accompanied by activation of the IRS. It in hypothesized that increased production of pro inflammatory cytokines could play a role association with the pathophysioly of epilepsy and autism and may be used in therapy

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 some biochemical and genetic markers in childhood simple obesity

This study was done to investigate the role of serum insulin, serum leptin, plasma adiponectin and lipoprotein lipase [LPL] Hind Ill gene polymorphism in childhood simple obesity for the development of group of disorders known as metabolic cardiovascular syndrome [MCS] which consists of an increased risk of hypertension, adverse lipid profile and early atherosclerotic lesions. This study was carried out on 20 children [6 boys and 14 girls] with simple obesity the diagnosis of simple obesity was based on the presence of body mass index [BMI] > 95[th] percentile with the exclusion of secondary obesity, their age was 8.2 +/- 2.28 years. Another 20 normal healthy children of matched age and sex served as a control group. All the studied groups were subjected to full clinical examination, anthropometric measurements, and estimation of blood glucose, lipid profile, serum insulin, serum leptin, plasma adiponectin as well as DNA analysis for detection of LPL Hind Ill gene polymorphism. Children with simple obesity showed significant increases in BMI, both systolic and diastolic blood pressure [SBP and DBP], serum triglycerides [TG], total cholesterol [TC], low-density lipoprotein cholesterol [LDL-c], serum insulin and serum leptin levels. On the other hand they showed significant decreases in high-density lipoprotein cholesterol [HDL-c] and plasma adiponectin levels. Adverse lipid profile [high TG and low HDL-c], and/or elevated blood pressure were positively correlated with serum insulin and serum leptin but negatively correlated with plasma adiponectin. There was no significant difference in Hind Ill LPL gene frequency between obese children and control group. Adverse lipid profile and hyperinsulinemia were associated with LPL Hind Ill polymorphism. This association was highest with [+/+] genotype, intermediate with [ +/- ] genotype and lowest with [-/-] genotype. In conclusion: hyperinsulinemia, hypeileptinemia, hypoadiponectinemia and the [H+] allele of the LPL Hind Ill polymorphism are closely correlated with the adverse lipid profile and/or elevated blood pressure in children with simple obesity that are regarded as cardiovascular risk factors for adulthood atherosclerosis which may necessitate an early periodic monitoring of blood pressure and metabolic status as well as the future application of the promising therapeutic ability of adiponectin to increase insulin sensitivity in conjunction with its anti-inflammatory and anti-atherogenic properties