Plasma endothesin-1 and renin as predictor factors in schistosomal liver disease of children

Endotheh-1 [ET-1] is a mitogenic and a potent vasoconstrictor peptide. It affects the hemodynamics of the liver and plays a role in fibro genesis through activation of stellate cells. Also renin-angiotensin system, which is activated in liver cirrhosis, may play a role in the pathogenesis of portal hypertension associated with schistosomal liver disease. The role of plasma ET-1 and renin in schistosomal liver disease and their clinical significance remain largely under investigated particularly in children. This study included 20 patients attending Pediatric Department of National Liver Institute, Menoufyia University, or Pediatric Department of Tanta University Hospital. Their mean age was 10.2 +/- 2.1 years. A control group of 20 healthy children of matched age and sex was included in the study. For all study children, history, physical examination, urine and stool analysis, CBC, kidney function tests and liver function tests were undertaken. Rectal snip biopsy, abdominal ultrasound examination and liver biopsy were utilized to diagnose our patients. Plasma ET-4 and renin were measured by radioimmunoassay. The mean level of ET-1 in the control group was 0.83 +/- 0.20 pg/ml with a range of 0.49 to 0.99 pg/ml, In contrast, the mean ET-1 level in the patients group was 1,37 +/- 0.6 pg/ml with a range of 0.49 to 2.24 pg/ml. The difference was statistically significant [p=0.001]. ET-1 was found to be elevated [2 SD above the mean control value] in 9 of 20 patients [45 %] with mean of 7.8 +/- 0.37 pg/ml and a range of 1.49 to 2.24 pg/ml. ET-1 was elevated in 2/11 [19%] of patients with hepatomegaly, in 2/3 [67%] of patients with hepatosplenomegaly, in the only case with shrunken liver 1/1 [100%] and in 4/5[80%] of patients with ascites. The relation of ET-1 elevation to the stage of disease was statistically significant [p=0.026]. Elevated ET-1 was found in 6/1 [86%] of patients with elevated ALT, compared with 3/13 [23%] of patients with normal ALT. This relation was statistically significant [p=0.017]. Plasma ET-1 levels appeared to correlate with duration and severity of the disease. Unlike in cirrhotic patients previously reported, renin was normal in all studied cases with no significant difference between patients of all disease stages versus controls. in the control group the mean plasma renin level was 2.52 +/- 1.23 ng/L and ranged from 1.23 to 3.81 ng/L while in the patients group it was 2.09 +/- 1.06 ng/L and ranged from 0.72 to 3.45 ng/L. This might be attributed to the stable hemodynamics and normal renal function of our study cases

Conclusions: the present study suggests that ET-7 level might be elevated in cases of schistosomal liver disease of Egyptian children particularly advanced cases. Elevated ET-1 might be involved in the aggravation of the disease or development of complications like portal hypertension 3rd ascites. So, monitoring ET-1 level along the course of the disease may be useful as a predictor for the development of these complications and may be helpful in the prevention planning. Plasma renin measurement probably has no important role in following up schistosomal liver disease during childhood

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