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In the management of severe pediatric brain injury, attention has previously been paid to brain edema, ICP elevation and low cerebral perfusion pressure (CPP). However, in the acute stage within 3-6 hours after trauma, brain hypoxia and hyperglycemia associated with diffuse brain injury are often observed. We have pointed out brain thermo-pooling (elevation of brain tissue temperature) and brain hypoxia caused by defective release of oxygen from hemoglobin (due to decrease in red blood cell enzyme (DPG)) as a new mechanism of brain injury. To treat these pathologic changes, we have developed a brain hypothermia treatment, the major purpose of which is to prevent brain hypoxia, brain thermo-pooling, neurohormonal changes causing cytokine encephalopathy, and a selective, radical-mediated damage of the dopamine A10 nervous system. The brain tissue temperature is initially adjusted to 35 degrees C with adequate cerebral oxygenation, followed by brain hypothermia at 34 degrees C for 1 weeks to prevent brain hypoxia, free radical reactions, brain edema and ICP elevation. What is most difficult in the pediatric brain hypothermia treatment is to maintain metabolic balance in the injured brain tissue and pulmonary infections associated with an immune crisis. When a rapid elevation of serum glucose is noted it is critical to lower the value because glucose quickly penetrates the blood-brain barrier and increases pyruvate and lactate by inhibiting the TCA cycle metabolism. Thus, hyperglycemia during brain hypothermia treatment is one of the major target of management. Another problem is immune crisis associated with secondary pulmonary infections. To prevent them, early enteral nutrition and replacement of L-arginine were most useful, as well as preconditioning for rewarming as follows: serum albumin > 3.0 g/dl; lymphocyte > 1500/mm3; T-H (CD4) lymphocytes > 55%; serum glucose, 120-140 mg/dl; vitamin A > 50 mg/dl; Hb > 12 g/dl and 2,3 DPG, 10-15 mumol/gHb; O2 ER, 23-25% and AT-III, > 100%. The clinical benefit of this therapy is still controversial.
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PMID:[Brain hypothermia treatment for the management of severe pediatric brain injury]. 1072 86

Selenium (Se) is an essential micronutrient for human and animal organisms. Organic selenium complexes and selenium-containing amino acids are considered the most bioavailable. Under appropriate conditions yeasts are capable of accumulating large amounts of trace elements, such as selenium, and incorporating them into organic compounds. It has been found that introduction of water-soluble selenium salt as a component of the culture medium for yeasts produced by conventional batch processing results in a substantial amount of selenium being absorbed by the yeast. Using a culture medium supplemented with 30 microg/mL sodium-selenite added during the exponential growth phase results in selenium-accumulation in the range of 1200-1400 microg/g dried baker's yeast (Saccharomyces cerevisiae) measured by ICP-AES method. In our previous studies it was shown that higher amounts of sodium-selenite in the culture medium have a strong inhibitory effect on the growth of this yeast. As a consequence of variations in cultivation conditions we obtained selenium yeast with different inorganic selenium content. The most important parameters influencing incorporated forms of selenium are pH value and dissolved oxygen level in the culture medium, and depending on these the selenium consumption rate of the yeast. A 0.40-0.50 mg/g h-1 specific selenium consumption rate was found to be appropriate to obtain selenium-enriched bakers' yeast of a high quality. Under suitable conditions the undesirable inorganic selenium content of the yeast could be suppressed to as low as 5-6% at the expense, however, of approximately a 20% decrease in the final biomass.
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PMID:Preparation of selenium yeasts I. Preparation of selenium-enriched Saccharomyces cerevisiae. 1083 33

High-dose barbiturate therapy is efficacious in lowering ICP and decreasing mortality in the setting of uncontrollable ICP refractory to all other conventional medical and surgical ICP-lowering treatments. Utilization of barbiturates for the prophylactic treatment of ICP is not indicated. The potential complications attendant on this form of therapy mandate that its use be limited to critical care providers and that appropriate systemic monitoring be undertaken to avoid or treat any hemodynamic instability. When barbiturate coma is utilized, consideration should also be given to monitoring arteriovenous oxygen saturation as some patients treated in this fashion may develop oligemic cerebral hypoxia.
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PMID:The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Use of barbiturates in the control of intracranial hypertension. 1093 96

We report the utility of native-state mass spectrometry to detect zinc ion binding to the engineered hemoglobin rHb52. Various preparations of this recombinant hemoglobin had significantly different oxygen affinities. Detailed characterization of denatured globins did not show any difference between analyzed hemoglobin molecules. However, when solutions of intact hemoglobin pseudotetramers were analyzed by native-state electrospray mass spectrometry, a significant shift in the mass spectrum was observed, indicating labile modification of hemoglobin. Using collision-induced dissociation (CID), we found a mass gain of 63 Da located on the beta-globin. EDTA treatment of modified hemoglobin prior to the infusion removed the modification and restored the predicted oxygen affinity. Ion-trap fragmentation of the +8 charged ion of modified beta-globin showed a neutral loss of 96+/-1 Da, consistent with neutral loss of zinc sulfide. These findings indicated zinc binding to the beta-globin through a cysteine residue. Involvement of Cys93 was confirmed by kinetics of cysteine residue reactivity with dithiodipyridine and peptide mapping. Presence of zinc was confirmed by ICP-MS metal analysis.
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PMID:Application of native-state electrospray mass spectrometry to identify zinc-binding sites on engineered hemoglobin. 1096 7

Since its development more than twenty years ago, non-invasive near-infrared-spectroscopy (NIRS) has been widely used to monitor cerebral oxygenation. Despite of its growing number of users, the diagnostic value of near-infrared spectroscopy still remains unclear, especially in case of acute brain injury and long-term neuromonitoring, necessary during intensive care therapy. To evaluate quality and sensitivity of NIRS measurements compared to invasive ICP-, CPP- and regional brain tissue--pO2 (p(ti)O2) monitoring, 31 patients, suffering from severe brain injury due to subarachnoid hemorrhage or severe head injury, were studied. NIRS measurements were only possible in 80% (using the INVOS oximeter) and in 46% (using the CRITIKON monitor), while good data quality was obtained in 100% from ICP, CPP and p(ti)O2. Major reasons for the failure of NIRS measurements were: (1) a wet chamber between sensor and skin, (2) galea hematoma or (3) subdural air after craniotomy. Different tests were performed to compare the sensitivity of regular oxygen saturation (NIRS) with the sensitivity of invasively determined p(ti)O2. Only induced hyperoxia (FiO2 = 1.0) revealed a significant correlation between both parameters (r = 0.67, p < 0.01). Lower or no correlation was found after changing paCO2 and administration of mannitol. The high failure rate and the limited sensitivity does not make the clinical use of near-infrared spectroscopy suitable as a part of neuromonitoring after acute brain injury at the present time.
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PMID:Near-infrared spectroscopy--not useful to monitor cerebral oxygenation after severe brain injury. 1098 54

Since 1992 the Consultative Committee on Road Traffic Fatalities in Victoria (CCRTF) has examined the medical management of patients who died following motor vehicle accidents. Three hundred and fifty-five fatalities with head injury occurring between 1 July, 1992 and 31 December 1997 were assessed by the CCRTF. They represented 79% of the total 449 fatalities examined by the Committee. Following examination of the complete medical records and multidisciplinary discussion, the Committee considered 237 (67%) of the 355 neurotrauma deaths to be non-preventable, 105 (30%) potentially preventable and 13 (4%) preventable. The present analysis excludes the non-preventable deaths in order to focus on preventable factors. Problems identified in the 118 patients pre-hospital included: no intubation; prolonged scene time; and no intravenous access; in 139 emergency room attendances: inappropriate reception including delay in arrival of a consultant, no neurosurgical consultation, no CT scan of the head, inadequate blood gases and oxygen monitoring, inadequate fluid resuscitation, delayed respiratory resuscitation and delayed dispatch to the operating room; in 111 operating room visits: no ICP monitoring, inadequate fluid administration and inappropriate anaesthetic technique; and in 90 intensive care unit admissions: no ICP monitoring. Overall, 1745 individual problems in the various areas of care were identified, of which 1104 (63%) were judged to have contributed to death. Improved delivery and quality of trauma care could reduce the identified problems in emergency services and clinical management. Basic principles of trauma management remain the most important means of reducing morbidity and death following road trauma. The leadership role of the neurosurgeon in neurotrauma care is emphasised.
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PMID:The preventability of death in road traffic fatalities with head injury in Victoria, Australia. The Consultative Committee on Road Traffic Fatalities. 1102 31

We used steady-state susceptibility contrast MRI to evaluate the regional cerebral blood volume (rCBV) response to hypocapnia in anesthetised rats. The rCBV was determined in the dorsoparietal neocortex, the corpus striatum, the cerebellum, as well as blood volume in extracerebral tissue (group 1). In addition, we used laser-Doppler flow (LDF) measurements in the left dorsoparietal neocortex (group 2), to correlate changes in CBV and in cerebral blood flow. Baseline values, expressed as a percentage of blood volume in each voxel, were higher in the brain regions than in extracerebral tissue. Hypocapnia (P(a)CO(2) approximately 25 mmHg) resulted in a significant decrease in CBV in the cerebellum (-17 +/- 9%), in the corpus striatum (-15 +/- 6%) and in the neocortex (-12 +/- 7%), compared to the normocapnic CBV values (group 1). These changes were in good agreement with the values obtained using alternative techniques. No significant changes in blood volume were found in extracerebral tissue. The CBV changes were reversed during the recovery period. In the left dorsoparietal neocortex, the reduction in LDF (group 2) induced by hypocapnia (-21 +/- 8%) was in accordance with the values predicted by the Poiseuille's law. We conclude that rCBV changes during CO(2) manipulation can be accurately measured by susceptibility contrast MRI. Abbreviations used: ANOVA analysis of variance CBF cerebral blood flow CBV cerebral blood volume CPMG Carr-Purcell-Meiboom-Gill FiO(2) fractional inspired oxygen ICP intracranial pressure LDF laser-Doppler flow MABP mean arterial blood pressure MRI magnetic resonance imaging MTT mean transit time PaCO(2) arterial partial pressure of carbon dioxide PaO(2) arterial partial pressure of oxygen PET positron emission tomography rCBV regional cerebral blood volume SPECT single-photon emission computed tomography
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PMID:Regional cerebral blood volume response to hypocapnia using susceptibility contrast MRI. 1111 61

A speciation technique for arsenic has been developed using an anion-exchange high-performance liquid chromatography/inductively coupled argon plasma mass spectrometer (HPLC/ICP MS). Under optimized conditions, eight arsenic species [arsenocholine, arsenobetaine, dimethylarsinic acid (DMA(V)), dimethylarsinous acid (DMA(III)), monomethylarsonic acid (MMA(V)), monomethylarsonous acid (MMA(III)), arsenite (As(III)), and arsenate (As(V))] can be separated with isocratic elution within 10 min. The detection limit of arsenic compounds was 0.14-0.33 microg/L. To validate the method, Standard Reference Material in freeze-dried urine, SRM-2670, containing both normal and elevated levels of arsenic was analyzed. The method was applied to determine arsenic species in urine samples from three arsenic-affected districts of West Bengal, India. Both DMA(III) and MMA(III) were detected directly (i.e., without any prechemical treatment) for the first time in the urine of some humans exposed to inorganic arsenic through their drinking water. Of 428 subjects, MMA(III) was found in 48% and DMA(III) in 72%. Our results indicate the following. (1) Since MMA(III) and DMA(III) are more toxic than inorganic arsenic, it is essential to re-evaluate the hypothesis that methylation is the detoxification pathway for inorganic arsenic. (2) Since MMA(V) reductase with glutathione (GSH) is responsible for conversion of MMA(V) to MMA(III) in vivo, is DMA(V) reductase with GSH responsible for conversion of DMA(V) to DMA(III) in vivo? (3) Since DMA(III) forms iron-dependent reactive oxygen species (ROS) which causes DNA damage in vivo, DMA(III) may be responsible for arsenic carcinogenesis in human.
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PMID:Identification of dimethylarsinous and monomethylarsonous acids in human urine of the arsenic-affected areas in West Bengal, India. 1130 25

In the 25 years since the 'Talk and Die' paper there have been substantial advances in the management of patients with severe closed head injury. This paper discusses developments in understanding of primary and secondary injury. Current management focuses on preventing secondary brain injury. That this has been successful is illustrated by a fall in mortality in recent decades. Evidence based guidelines have set standards of management but they do not take into account variations between individuals, between regions of the brain and variations with time from injury. Various monitoring techniques such as transcranial doppler, jugular venous oxygen saturation and ICP waveform analysis attempt to set individual therapeutic endpoints and to target therapy appropriately. Primary injury is no longer seen as a single irreversible event occurring at the time of impact, but rather as a process initiated by the impact and evolving over subsequent hours and days. Experimental studies have identified agents which reduce the evolution of brain injury and improve outcome. An experimental model of brain injury developed by the Adelaide He ad Injury Group identifies diffuse axonal injury as a target for therapeutic manipulation. Magnesium has been shown in other studies to improve outcome after diffuse brain injury. This has now been linked with upregulation of beta amyloid precursor prote in. Although this and several other experimental therapies have shown great promise, they have not so far produced benefit in large clinical studies. Avoiding secondary insults will remain the goal of management for the foreseeable future. Halting the evolution of the primary injury remains a highly sought after goal. Although elusive so far, it is likely to be the next major advance in clinical care.
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PMID:Brain injury: the pathophysiology of the first hours.'Talk and Die revisited'. 1153 3

A controlled environment system, termed the Phyto-Nutri-Tron (PNT), has been established to study whole plant ecophysiological responses to multiple environmental factors. The PNT is a computer-controlled highly flexible growth facility with independent control of the shoot and the root environment. The facility consists of two growth cabinets each containing four separate hydroponic growth systems. The growth cabinets can be used as assimilation chambers with individual control of temperature, humidity, light, CO2 and monitoring of O2. The hydroponic growth systems are connected to nutrient supply units with disinfection systems and individual control of temperature, pH and oxygen. The ionic composition of the solutions has automated feedback control through a PO4 autoanalyzer and a flow injection analyzer which also analyzes NH4+, NO2- and NO3-. Other ions are automatically monitored by ICP-AES. The system has automated calibration procedures of the analytical equipment and prolonged studies of plant growth can be performed under constant environmental conditions. This paper describes the design and construction of the PNT, the results of a number of tests showing the degree of control of environmental factors and the results of a comparative study on NH4+ and NO3- uptake kinetics by Juncus effusus conducted in the PNT demonstrate the use of the PNT in ecophysiological studies.
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PMID:Design and performance of the Phyto-Nutri-Tron: a system for controlling the root and shoot environment for whole-plant ecophysiological studies. 1154 49


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