Serum levels of platelet-activating factor, platelet-activating factor acetylhydrolase, and tumor necrosis factor-alpha in neonates with necrotizing enterocolitis before and after treatment

Because previous investigations have suggested that platelet activating factor, and tumor necrosis factor,-alpha [TNF-alpha] are thought to be important mediators of experimental necrotizing enterocolitis in animals, we measured platelet activating factor [PAF], PAF-acetylhydrolase [PAF-AHs], and TNF-alpha in the serum of 23 human neonates with necrotizing enterocolitis before and 2 weeks after treatment and 14 age-matched control subjects with similar gestational ages, postnatal ages, and weights. Patients included in this study were studied from June 2002 to May 2004 at Neonatal Intensive Care Unit of Tanta University Hospital, Egypt Almost all patients with necrotizing enterocolitis had elevated serum platelet activating factor values [17.9 +/- 4.1 ng/ml vs. 3.7 +/- 0.8 ng/ml in control subjects, p < 0.01]. Serum acetylhydrolase activity was lower in patients than in control subjects [11.2 +/- 0.6 nmol/ml/min vs. 24.9 +/- 2.1 nmol/ml/min, p < 0.01]. Serum TNF-alpha concentration was significantly elevated in patients with necrotizing enterocolitis [119.2 +/- 63.1 U/ml vs. 5.7 +/- 1.7 U/ml, p < 0.01]. There were no significant differences between serum levels of PAF, TNF-alpha, and PAF-AHs between controls and survived patients 2 weeks after treatment, p>0.05. Also there were no significant differences between serum levels of PAF, TNF-alpha and PAF-AHs on admission between dead and survived patients, p>0.05. There was no correlation between individual platelet activating factor levels and both TNF-alpha and PAF-AHs levels in patients. We concluded that platelet activating factor and TNF-alpha are elevated in patients with necrotizing enterocolitis and that reduced platelet activating factor degradation contributes to the increased platelet activating factor levels, which together with TNF-alpha may con tribute to the pathophysiology of necrotizing enterocolitis in human neonates. The use of agents that antagonize or contain degrading factors of PAF might provide therapeutic and/or prophylactic options in the management of NEC

Risk of epilepsy after electrographically proven neonatal seizures

Neonatal seizures often are manifestations of significant neurological disease and major predictors of adverse neurological outcome in the newborn. The present work aimed at estimation of outcomes of neonatal seizures especially the development of epilepsy. The present study was conducted on 30 patients [15 males and 15 females] with neonatal seizures, their ages ranged from one to 30 days. All patients were subjected to full history taking and through clinical examination. Laboratory investigations included: complete blood picture, metabolic screening tests [blood glucose, serum Ca, Mg and Na, blood urea, serum creatinine, serum bilirubin and ferric chloride test], sepsis screen [blood, CSF and urine culture, and TORCH titers], brain C. T. scan and EEG [interictal and follow up]. The etiologic diagnosis of neonatal seizures was based on positive clinical data, laboratory data and/or imaging data. Follow up for at least 6 months was performed with serial neurological evaluation and EEG. From this study, it was found that the seizures etiologies were diverse, hypoxic ischemic encephalopathy [HIE] was the most common cause 46.7%, meningitis 16.7%, cerebral dysgenesis 10%. Metabolic causes 13.3% and intracranial hemorrhage 13.3%. Etiology of seizures was significantly correlated with total outcome, subsequent development of epilepsy and developmental delay. There was significant correlation between findings of neurological examination and total outcome, epilepsy and developmental delay. Neonates with mildly abnormal neurological findings had favorable outcome in 100% of cases. Patients with severely abnormal neurological findings were associated with unfavorable outcome [mortality, epilepsy or developmental delay] in 81.8% of cases. Type of seizures was significantly correlated with the total outcome and mortality. Generalized tonic seizures had the worst prognosis. There was significant correlation between brain CT findings and total outcome, subsequent development of epilepsy and developmental delay. EEG findings were significantly correlated with the outcomes findings of neurological examination and frequency of seizures but insignificantly correlated with type of seizures, onset of seizures and brain CT findings. The 3-months follow up EEG was significantly correlated with the development of epilepsy. Seizure etiology, neurological evaluation of the newborn at birth [mildly, moderately and severely abnormal], clinical characteristics of seizures [onset, frequency and types], brain CT. and EEG findings [interdicted EEG background activity], 3-months follow-up EEG and meticulous follow-up clinical examination were the most important determinants for prediction of the neurological outcome of neonatal seizures. Epilepsy and developmental delay after neonatal seizures were more frequent in presence of one or more of the following: severely abnormal neurological examination at birth, cerebral dyesgenesis as an etiology of seizures, generalized tonic seizures, seizure frequency >/= 2 seizures/h, abnormal brain CT scan findings and abnormal inter-ictal EEG background. EEG is recommended to be performed for all cases with neonatal convulsions as a diagnostic and prognostic tool. Meticulous follow up [clinical examination, EEG] of cases with neonatal seizures is essential to predict the subsequent development of epilepsy and developmental delay

Neonatal cerebrospinal fluid plasminogen and plasminogen activator inhibitor-1 assay as predictors of post hemorrhagic hydrocephalus

Massive intraventricular hemorrhage [IVH] in neonates is followed by progressive ventricular dilatation in 55-80% of cases if the infant survives. The initial mechanism of post hemorrhagic hydrocephalus [PHH] is thought to be obstruction by multiple small blood clots of the channels of the cerebrospinal fluid [CSF] to areas of absorption. Plasminogen activator inhibitor-1 [PAI-1] is the principal regulator of fibrinolysis in blood and one of the most highly controlled of the fibrinolytic components. The aim of this study is to measure plasminogen and plasminogen activator inhibitor-1 levels in the CSF of the neonates after IVH to assess endogenous fibrinolytic activity and to predict the development of post hemorrhagic hydrocephalus. Fifteen full term and preterm neonates with IVH were enrolled in the study. Ten neonates without IVH were used as a control group. Cranial ultrasound was performed at age of 2 weeks and 2 months. Plasma and CSF plasminogen and PAI-1 levels were assessed for these neonates. The results revealed that CSF PAI-1 was significantly higher in infants with IVH than in the controls [P<0.001]. There was no significant difference in the CSF and plasma plasminogen between infants with IVH and controls [p>0.05]. CSF PAI-1 was significantly higher in infants with PHH than in infants with post hemorrhagic ventricular dilatation [p<0.05], with a sensitivity [100%] and specificity [100%]. CSF PAI-1 is a very sensitive and specific parameter than CSF plasminogen for prediction of PHH in neonates with IVH, and this might be useful to evaluate the specific therapeutic programs of these neonates

Plasma natriuretic peptides as predictors of hemodynamically significant patent ductus arteriosus in preterm neonates

The objective of this study was to determine whether the plasma levels of natriuretic peptides in preterm infants with patent ductus arteriosus [PDA] are predictors of the hemodynamic significance of the PDA shunt, and correlate them with clinical and echocardiographic assessment. Fifty preterm neonates, with a mean gestational age of 29.4 wk and weighing less than 1500 g, were enrolled in the study. Based on the clinical and echocardiographic findings, the hemodynamic influence of PDA shunt was classified as: large [8 infants], moderate [10 infants], small [12 infants] or no PDA [20 infants]. Plasma N-terminal atrial natriuretic peptide prohormone [Nt-pro ANP] and brain natrituretic peptide [BNP] were assessed using ELISA kits. The results showed that plasma levels of Nt-pro ANP and BNP significantly increased with the size of PDA shunt, and when compared to infants without PDA [P<0.05]. A value of Nt-pro ANP > 5000 pmol/l predicted a hemodynamically significant PDA with a sensitivity of 97% and a specificity of 90%, whereas a value of BNP > 25 pmol/l had a sensitivity of 87% and a specificity of 75%. Using echocardiographic left atrial/aortic root ratio [LA: Ao ratio] of 1.5 as a cut off gave a sensitivity of 75%. Using echocardiographic left atrial/aortic root ratio [LA: Ao ratio] of 1.5 as a cut off gave a sensitivity of 80% and a specificity of 95%. There were significant positive correlations between these studied parameters [P<0.01]. Plasma naturiuretic peptides [Nt-pro ANP and BNP] can be used as predictors of the hemodynamic significance of PDA in preterm neonates, and their measurement may be regarded as complementary to echocardiography in the assessment of PDA shunt and institution of appropriate treatment. Nt-pro ANP is more sensitive and specific predictor than BNP

Relationship of Monocyte chemoattractant protein-1 with diabetic nephropathy in children with type-1 diabetes: effect of high dose vitamin E therapy

Monocyte chemoattractant protein-1 [MCP-1] is a specific chemokine that activates monocytes from the circulation to the inflammatory sites. In diabetic nephropathy, similar to other glomerulonephropathies, infiltration and activation of monocytes / macrophages in the glomeruli have been implicated in the development of glomerular injury. The aim of this study was to examine a possible relationship of the MCP-1 with the development of diabetic nephropathy in children with type-1 diabetes before and after treatment with high dose of vitamin E for eight weeks. This study was carried out on thirty diabetic children, group 1; fifteen children with type 1 diabetes mellitus with persistent microalbuminuria, and group 2; fifteen children without microalbuminuria. Fifteen healthy children served as control group. Albumin excretion rate [AER] and glycosylated hemoglobin [HbA[1C]] were measured, also plasma MCP-1 levels were measured by ELISA before and after treatment with vitamin E for eight weeks. The results proved that plasma levels of MCP-1 were significantly higher in children with diabetic nephropathy than diabetic children without nephropathy and the control group [P<0.05]. There was strong positive correlation between HbA[1C] level and AER and MCP-1 [P<0.0001]. After treatment with vitamin E, there was a significant decrease in the MCP-1 plasma levels in diabetic children with nephropathy. This study suggests that facilitated MCP-1 production by the mesangial cells in diabetic children contributes to the initiation and progression of diabetic nephropathy. High-dose vitamin E supplementation may provide an additional benefit, as adjuvant therapy to insulin treatment, in reducing the risks for the development of diabetic nephropathy

Study on the prevalence of congenital in neonates with Jaundice

Toxoplasmosis is an infectious disease of world wide distribution caused by the protozoan Toxoplasma gondii. It infects all species of mammals and birds. The present study aimed to study the prevalence of congenital toxoplasmosis in neonates with jaundice estimation of anti-Toxoplasma antibodies [IgG and IgM] in neonates with jaundice by the indirect haemagglutination test [IHAT] and the enzyme linked immunosorbant assay [ELISA]. The study was done on 78 neonates with jaundice [Group I] and ten healthy neonates as a control group [Group II] with estimation of anti-Toxoplasma antibodies [IgG and IgM] in all selected neonates by the indirect haemagglutination test [IHAT] and the enzyme linked immunosorbant assay [ELISA]. In group I anti- Toxoplasma IgG was positive in 23 cases [29.4%] while anti-Toxoplasma IgM was positive in 10 cases [12.8%]. In group II anti-Toxopasma IgG was positive in one case [10%] and anti- Toxoplasma IgM was negative. From the present study we concluded that congenital toxoplasmosis must be born in mind in the differential diagnosis of neonatal jaundice. Serodiagnosis of toxoplasmosis should be done in neonates for early detection of subclinical cases and early treatment to reduce the severe long-term sequelae

Evaluation of the dose - response potency of intrathecally administered clonidine by itself during first stage of labor with respect to analgesia and maternal and fetal side effects

Intrathecal clonidine produces dose-dependent postoperative analgesia and enhances labor analgesia from intrathecal sufentanil. We evaluated the dose-response potency of intrathecally administered clonidine by itself during first stage of labor with respect to analgesia and maternal and fetal side effects. Forty-five parturients requesting labor analgesia were studied. In a combined spinal-epidural technique, patients with <5 cm cervical dilatation were assigned to receive one of the following intrathecal solutions: either 75 micro g clonidine [n = 15]; 150 micro g clonidine [n = 15]; and 250 micro g clonidine [n = 15]. Visual analog scores for pain, blood pressure, heart rate, ephedrine requirements, sensory levels, incidence of nausea, pruritus and sedation, fetal heart rate tracings continuously, and maternal and cord blood concentrations of clonidine were recorded. Duration of analgesia was defined as time from intrathecal clonidine administration until request for additional analgesia. We found that clonidine produced a reduction in VAPS with all three doses. The duration of analgesia was significantly longer in patients receiving 250 micro g [median, 150; range, 85-220 min] and 150 micro g [median, 120; range; 65-190 min] than 75 micro g [median 50; range, 30 - 160 min], and VAPS was lower in the 250 micro g than in the 75 micro g group. As regards the sensory levels, no patient in any group had sensory changes above T[3]. In the 250 micro g group, hypotension required significantly more often treatment with ephedrine than in the other groups. Also, bradycardia and sedation were more in 250 micro g group than the other two groups. No adverse events or fetal heart rate abnormalities occurred. Clonidine levels were undetectable in maternal and cord serums. In conclusion, the current study showed that 75 micro g to 250 micro g intrathecal clonidine produces dose-dependent analgesia during first stage of labor. Although duration and quality of analgesia were more pronounced with 150 and 250 micro g than with 75 micro g, the high incidence of hypotension, bradycardia and sedation requires caution with the use of 250 micro g for labor analgesia