Mohamed Elgamal

Can thoracic paravertebral block replace thoracic epidural block in pediatric cardiac surgery? A randomized blinded study

To compare the outcomes of thoracic epidural block with thoracic paravertebral block for thoracotomy in pediatric patients. A prospective double-blind study. 60 pediatric patients aged 1-24 months, ASA II, III scheduled for thoracotomy were randomly allocated into two groups. After induction of general anesthesia, thoracic epidural catheter was inserted in group E (epidural) patients and thoracic paravertebral catheter was inserted in group P (paravertebral) patients. Post operative pain score was recorded hourly for 24 hours. Plasma cortisol level was recorded at three time points. Tidal breathing analysis was done preoperatively and 6 hours postoperatively. Analgesia, serum cortisol level, and pulmonary function parameters were comparable in the two groups. However, failure rate (incorrect placement of catheter) was significantly higher in epidural group than in paravertebral group (7% versus 0%, respectively). The complications were also significantly higher in epidural group (vomiting 14.8%, urine retention 11.1% and hypotension 14.8%) than paravertebral group (0%, 0%, and 3.6%, respectively). We conclude that both thoracic paravertebral block and thoracic epidural block results in comparable pain score and pulmonary function after thoracotomy in pediatric patients; the paravertebral block is associated with significantly less failure rate and side effects.

Mitochondrial complex I inhibition as a possible mechanism of chlorpyrifos induced neurotoxicity.

Background Organophosphates (OPs) represent the most widely used class of pesticides. Although perceived as low toxicity compounds compared to the previous organochlorines, they still possess neurotoxic effects both on acute and delayed levels. Delayed neurotoxic effects of OPs include OPIDN and OPICN. The mechanisms of these delayed effects have not been totally unraveled yet. One possible contributor for neurotoxicity is mitochondrial complex I (CI) inhibition. Purpose in the present study we evaluated the contributing role of (CI) inhibition in chlorpyrifos (CPF) induced delayed neuropathy in hens. Methods Experimented birds received 150 mg/kg of CPF, and evaluated behaviorally and biochemically. Results CPF treated hens received 150 mg/kg and developed signs of delayed neurotoxicity, which were verified by NTE inhibition. These effects were paralleled by CI inhibition and decrease in ATP level. Conclusions The data confirms the possible role of CI inhibition in CPF induced delayed neuropathy.

Developmental neurotoxic effects of Malathion on 3D neurosphere system

Developmental neurotoxicity (DNT) refers to the toxic effects induced by various chemicals on brain during the early childhood period. As human brains are vulnerable during this period, various chemicals would have significant effects on brains during early childhood. Some toxicants have been confirmed to induce developmental toxic effects on CNS; however, most of agents cannot be identified with certainty. This is because available animal models do not cover the whole spectrum of CNS developmental periods. A novel alternative method that can overcome most of the limitations of the conventional techniques is the use of 3D neurosphere system. This in-vitro system can recapitulate many of the changes during the period of brain development making it an ideal model for predicting developmental neurotoxic effects. In the present study we verified the possible DNT of Malathion, which is one of organophosphate pesticides with suggested possible neurotoxic effects on nursing children. Three doses of Malathion (0.25 μM, 1 μM and 10 μM) were used in cultured neurospheres for a period of 14 days. Malathion was found to affect proliferation, differentiation and viability of neurospheres, these effects were positively correlated to doses and time progress. This study confirms the DNT effects of Malathion on 3D neurosphere model. Further epidemiological studies will be needed to link these results to human exposure and effects data.

Neural substrates and potential treatments for levodopa-induced dyskinesias in Parkinson's disease.

Abstract Parkinson’s disease (PD) is primarily a motor disorder that involves the gradual loss of motor function. Symptoms are observed initially in the extremities, such as hands and arms, while advanced stages of the disease can effect blinking, swallowing, speaking, and breathing. PD is a neurodegenerative disease, with dopaminergic neuronal loss occurring in the substantia nigra pars compacta, thus disrupting basal ganglia functions. This leads to downstream effects on other neurotransmitter systems such as glutamate, γ-aminobutyric acid, and serotonin. To date, one of the main treatments for PD is levodopa. While it is generally very effective, prolonged treatments lead to levodopa-induced dyskinesia (LID). LID encompasses a family of symptoms ranging from uncontrolled repetitive movements to sustained muscle contractions. In many cases, the symptoms of LID can cause more grief than PD itself. The purpose of this review is to discuss the possible clinical features, cognitive correlates, neural substrates, as well as potential psychopharmacological and surgical (including nondopaminergic and deep brain stimulation) treatments of LID.

Role of l-thyroxin in counteracting rotenone induced neurotoxicity in rats

A key feature of Parkinsons disease is the dopaminergic neuronal cell loss in the substantia nigra pars compacta. Many triggering pathways have been incriminated in the pathogenesis of this disease including inflammation, oxidative stress, excitotoxicity and apoptosis. Thyroid hormone is an essential agent for the growth and maturation of neurons; moreover, it has variable mechanisms for neuroprotection. So, we tested the efficacy of (L)-thyroxin as a neuroprotectant in rotenone model of Parkinsons disease in rats. Thirty Sprague Dawley rats aged 3 months were divided into 3 equal groups. The first received daily intraperitoneal injections of 0.5% carboxymethyl cellulose (CMC) 3 mL/Kg. The second group received rotenone suspended in 0.5% CMC intraperitoneally at a dose of 3 mg/kg, daily. The third group received the same rotenone regimen subcutaneous l-thyroxine at a dose of 7.5 μg daily. All animals were evaluated regarding locomotor disturbance through blinded investigator who monitored akinesia, catalepsy, tremors and performance in open field test. After 35 days the animals were sacrificed and their brains were immunostained against anti-tyrosine hydroxylase and iba-1. Photomicrographs for coronal sections of the substantia nigra and striatum were taken and analyzed using image J software to evaluate cell count in SNpc and striatal fibers density and number of microglia in the nigrostriatal system. The results were then analyzed statistically. Results showed selective protective effects of thyroxin against rotenone induced neurotoxicity in striatum, however, failed to exert similar protection on SN. Moreover, microglial elevated number in nigrostriatal system that was induced by rotenone injections was diminished selectively in striatum only in the l-thyroxin treated group. One of the possible mechanisms deduced from this work was the selective regulation of microglia in striatal tissues. Thus, this study provides an insight into thyroxin neuroprotection warranting further investigation as therapeutic option for Parkinsons disease patients.

Organophosphorus Flame Retardants (OPFR): Neurotoxicity

Organophosphorus flame retardants (OPFRs) are used as additives in plasticizers, foams, hydraulic fluids, anti-foam agents, and coatings for electronic components/devices to inhibit flames. These chemicals were developed and used as flame retardants because of environmental and health concerns of previously used brominated and chlorinated flame retardants (FRs). OPCFRs are divided into five main groups: organophosphates, organophosphonates, organophosphinates, organoposphine oxide, and organophosphites. Most of OPFRs are organophosphate esters that are further classified into the following five groups: 1. Aliphatic, 2. Brominated aliphatic, 3. Chlorinated aliphatic, 4. Aromatic-aliphatic, and 5. Aromatic phosphates. These OPFRs have the following neurotoxic actions: 1. Cholinergic Neurotoxicity, 2. Organophosphate-Induced Delayed Neurotoxicity (OPIDN), and 3. Organophosphate-Induced Chronic Neurotoxicity (OPICN) in addition to being endocrine disruptors. OPFRs have very low cholinergic neurotoxicity and this effect does not pose significant health hazards to adults or children. On the other hand, some OPFRs have shown to cause OPIDN that is a delayed central-peripheral axonopathy, characterized by neuronal cell death of the lower brain regions, spinal cord and peripheral nervous systems, leading to long-term neuronal injury. OPICN is characterized by neuronal cell death in the cortex, hippocampus campus and cerebellum and spinal cord. Finally, OPCFRs act as endocrine disrupters, that affect many functions of the body such thyroid glands and reproductive functions, and may be involved in the development of diabetes and cancer. Residues of these OPCFRs are widespread in the environment, home and workplaces. These chemicals adversely affect human health, especially for vulnerable population such as the elderly, pregnant women, fetuses, and children. Because some OPFRs cause neuronal cell death in the brain and spinal cord that do not repair as well as act as endocrine disrupters they may lead to permanent functional deficits such obesity, memory impairment, decreased motor skill and even more serious diseases such as diabetes and cancer. Because recent reports have accredited FRs for significant decrease in building fires, it is important to balance the risk and benefits of FRs and to use only the safest available FRs including OPFRs. *Corresponding author: Mohamed B. Abou-Donia, Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 277, USA, Tel: +919-68422/ Fax: 919-681-822, E-mail: donia@duke.edu Citation: Abou-Donia, M.B., et al. Organophosphorus Flame Retardants (OPFR): Neurotoxicity. (2016) J Environ Health Sci 2(1): 129. Organophosphorus Flame Retardants (OPFR): Neurotoxicity Mohamed B. Abou-Donia1* Mohamed Salama2, Mohamed Elgamal2, Islam Elkholi2,3, Qiangwei Wang1,4 Received date: July 07, 2015 Accepted date: May 05, 2016 Published date: May 11, 2016 DOI: 10.15436/2378-6841.16.022

Neurological outcome of normothermic versus hypothermic cardiopulmonary bypass in simple congenital heart diseases

Objective We hypothesized that normothermic cardiopulmonary bypass (CPB) may provide equivalent results to hypothermic CPB on neurological outcome. Patients and methods Forty patients were randomized to one of two groups: group 1 that underwent normothermic CPB (>35°C) and group 2 that underwent mild hypothermic CPB (32°C). Perfusion on bypass was performed by a nonpulsatile pump flow with an average flow rate around 2.4 l/m 2 /min. A pH-stat carbon dioxide management strategy was used. The arterial and jugular venous blood gases, mean cerebral blood flow velocity (CBFV), and pulsatile index were measured as basal, after induction of anesthesia, at the onset of CPB, 20-30-40 min after the CPB, at the cessation of CPB, and at the end of the operation. Neurological outcomes were assessed by computed tomography scanning and Wechsler Preschool and Primary Scale of Intelligence preoperatively, at the third postoperative day and 1 month after surgery. Postoperative ICU variables such as duration of mechanical ventilation, time to extubation, and ICU length of stay were recorded. Results There was a significant increase in SjvO 2 and decrease in CeO 2 in the hypothermia group of patients after establishment of hypothermia by 10 and 20 min when compared with the normothermic group (P < 0.05 and <0.01, respectively). The CeO 2 was maximal during normothermic CPB and after rewarming phase of hypothermic CPB. There were no significant changes in computed tomography scanning and Wechsler Preschool and Primary Scale of Intelligence between the studied groups at any time period. There was significant prolongation in duration of postoperative mechanical ventilation, extubation time, and duration of ICU stay in the hypothermic group of patients compared with the normothermic group (P < 0.05). Conclusion During CPB for correction of congenital heart defects, the normothermic and hypothermic CPB were comparable with respect to the neurological outcome. However, normothermia permits shorter time on mechanical ventilation, more rapid extubation, and shorter ICU stay time compared with hypothermia.

Monitoring the effects of propofol and sevoflurane on cerebral oxygen supply-demand balance using transcranial Doppler sonography and jugular bulb saturation in pediatric open heart surgery

Background Increasing awareness of neurologic abnormalities associated with congenital heart surgical intervention has heightened investigations for prevention of neurologic injury during the perioperative period. This study investigated the effects of propofol and sevoflurane on cerebral oxygen supply demand balance using transcranial Doppler sonography and jugular bulb saturation in pediatric open heart surgery. Methods After obtaining institutional approval and a written consent from parents, 60 children who were admitted for elective open cardiac surgery for correction of congenital heart disease using CPB were included in this study. Children were randomized into two groups; group (P) and group (S). Induction of Anesthesia was achieved by 5 μg/Kg I.V. fentanyl, propofol 2- 2.5 mg/Kg (in propofol or P group) or sevoflurane 2-3 MAC (in sevoflurane or S group). Anesthesia was maintained by propofol infusion between 75-100 μg/kg/min in P group or sevoflurane 2 MAC in S group. Calculated parameters from the blood gas variables included cerebral metabolic rate of oxygen (CMRO 2 ), cerebral extraction of oxygen (CeO 2 ) and cerebral blood flow equivalent (CBF). Arterial blood gases (ABG) and velocities of flow were monitored by Trancranial Doppler at 5 time points : before the surgery, before CPB, during CPB (after establishment of full flow), after CPB and after recovery. Neurological examination and CT scan were done before surgery and 2 days after that. Results There is no significant difference between the two groups in demographic data. Children in propofol group showed lower heart rate values after induction and after CPB than those in sevoflurane group. Mean arterial pressure was statistically higher in sevoflurane group compared with propofol group after induction. Children in sevoflurane group showed significantly higher; velocity maximum, velocity mean and pulsatile index, in the after induction and after bypass periods than those in propofol group. Velocity minimum showed no difference between the two groups. SjvO 2 , CMRO 2 , CeO 2 and CBF was significantly different after induction in sevoflurane group compared with propofol group. Perioperative blood gases showed no difference between the studied groups. Conclusion Compared with propofol anesthesia, sevoflurane anesthesia provides a wider margin of safety against impaired cerebral oxygenation and better preservation of systemic hemodynamics. Moreover, cerebral oxygen saturation may not reflect changes in cerebral oxygenation as monitored by jugular venous oxygen tension measurement in children undergoing CPB.

Does type of cardioplegia affect myocardial and cerebral outcome in pediatric open cardiac surgeries

Background A single-dose strategy for cardioplegia is desired in pediatric congenital cardiac surgery, especially in repair of complex congenital defects. The hypothesis of this study is that a single infusion of Bretschneider HTK solution may offer myocardial and cerebral protection superior to repeated doses of a cold oxygenated blood cardioplegic solution in pediatric congenital cardiac surgery. Patients and methods Sixty patients who underwent congenital cardiac repair using cardiopulmonary bypass were grouped randomly to receive either a single dose of Custodiol (group A) or repeated oxygenated blood cardioplegia (group B). Echocardiography, ECG, and microscopic examination were used to evaluate left-ventricular function and structure. Myocardial injury was assessed with creatine kinase MB and serum troponin T, whereas cerebral outcome was assessed by jugular venous oxygen saturation. Patients were also neurologically examined and studied by brain computed tomography for gross neurological manifestation of cerebral ischemia or infarction preoperative and 2 days postoperatively. Results Myocardial enzymes and oxygen extraction were significantly high in group B compared with group A. Ultrastructure evaluation and cerebral outcome were significantly better in group A than in group B. Conclusion A single dose of an HTK cardioplegic solution provides better myocardial and cerebral protection than repeated doses of oxygenated blood cardioplegia during pediatric congenital cardiac surgery.