Prosthetic rehabilitation of a bone defect with a teeth-implant supported, removable partial denture

The use of teeth-implant, mucosa-supported removable dentures for rehabilitation of partially edentulous patients involves highly complex biomechanical aspects. This type of prosthesis associates 3 kinds of support that react differently to the functional and parafunctional forces developed in the oral cavity. Although the construction of removable partial dentures may seem paradoxical when osseointegrated implants are placed, in some cases, this option is an excellent alternative to solve difficulties related to the anatomic, biologic, psychomotor, and financial conditions of the patient. This article reports on a case in which a teeth-implant, mucosa-supported removable partial denture was the option of choice for a patient with financial and anatomic limitations, having a large structural loss of the residual alveolar ridge caused by trauma by a gunshot injury at the mandible. The 5-year follow-up did not reveal any type of biomechanical or functional problem. Copyright © 2006 by Lippincott Williams and Wilkins.

Correction of malpositioned implants through periodontal surgery and prosthetic rehabilitation using angled abutment

When dental implants are malpositioned in relation to the adjacent teeth and alveolar bone or in an excessive buccal or lingual position, the final prosthesis rehabilitation impairs the peri-implant health of the gingival tissues and the aesthetics of the patient. Thus, the purpose of this case was to report and discuss a multidisciplinary protocol for the treatment of a compromised maxillary tooth in a patient with an abscess in his right central incisor due to an excessive buccal implant position. The patient presented with an implant-supported provisional restoration on his right maxillary central incisor and a traumatic injury in his left central incisor. The treatment protocol consisted in (i) abutment substitution to compensate the incorrect angulation of the implant, (ii) clinical crown lengthening, (iii) atraumatic extraction of the left central incisor, and (iv) immediate implant placement. Finally, (v) a custom abutment was fabricated to obtain a harmonious gingival contour around the prosthetic crown. In conclusion, when implants are incorrectly positioned in relation to the adjacent teeth, associated with soft-tissue defects, the challenge to create a harmonious mucogingival contours may be achieved with an interdisciplinary approach and with the placement of an appropriate custom abutment.

Knock out of neuronal nitric oxide synthase exacerbates intestinal ischemia/reperfusion injury in mice

Recent investigation of the intestine following ischemia and reperfusion (I/R) has revealed that nitric oxide synthase (NOS) neurons are more strongly affected than other neuron types. This implies that NO originating from NOS neurons contributes to neuronal damage. However, there is also evidence of the neuroprotective effects of NO. In this study, we compared the effects of I/R on the intestines of neuronal NOS knockout (nNOS(-/-)) mice and wild-type mice. I/R caused histological damage to the mucosa and muscle and infiltration of neutrophils into the external muscle layers. Damage to the mucosa and muscle was more severe and greater infiltration by neutrophils occurred in the first 24 h in nNOS(-/-) mice. Immunohistochemistry for the contractile protein, alpha-smooth muscle actin, was used to evaluate muscle damage. Smooth muscle actin occurred in the majority of smooth muscle cells in the external musculature of normal mice but was absent from most cells and was reduced in the cytoplasm of other cells following I/R. The loss was greater in nNOS(-/-) mice. Basal contractile activity of the longitudinal muscle and contractile responses to nerve stimulation or a muscarinic agonist were reduced in regions subjected to I/R and the effects were greater in nNOS(-/-) mice. Reductions in responsiveness also occurred in regions of operated mice not subjected to I/R. This is attributed to post-operative ileus that is not significantly affected by knockout of nNOS. The results indicate that deleterious effects are greater in regions subjected to I/R in mice lacking nNOS compared with normal mice, implying that NO produced by nNOS has protective effects that outweigh any damaging effect of this free radical produced by enteric neurons.

Texture analysis of high resolution MRI allows discrimination between febrile and afebrile initial precipitating injury in mesial temporal sclerosis

A computational pipeline combining texture analysis and pattern classification algorithms was developed for investigating associations between high-resolution MRI features and histological data. This methodology was tested in the study of dentate gyrus images of sclerotic hippocampi resected from refractory epilepsy patients. Images were acquired using a simple surface coil in a 3.0T MRI scanner. All specimens were subsequently submitted to histological semiquantitative evaluation. The computational pipeline was applied for classifying pixels according to: a) dentate gyrus histological parameters and b) patients' febrile or afebrile initial precipitating insult history. The pipeline results for febrile and afebrile patients achieved 70% classification accuracy, with 78% sensitivity and 80% specificity [area under the reader observer characteristics (ROC) curve: 0.89]. The analysis of the histological data alone was not sufficient to achieve significant power to separate febrile and afebrile groups. Interesting enough, the results from our approach did not show significant correlation with histological parameters (which per se were not enough to classify patient groups). These results showed the potential of adding computational texture analysis together with classification methods for detecting subtle MRI signal differences, a method sufficient to provide good clinical classification. A wide range of applications of this pipeline can also be used in other areas of medical imaging. Magn Reson Med, 2012. (c) 2012 Wiley Periodicals, Inc.

Influence of different types of seat cushions on the static sitting posture in individuals with spinal cord injury

Study design: Cross-sectional study. Objectives: To evaluate the efficacy of the Postural Assessment Software PAS/SAPO in the posture analysis of individuals with spinal cord injury (SCI) during sitting position and to analyze if the use of different types of seat cushions-gel and foam, with no cushion-can interfere in the individual's posture during sitting position. Setting: Centre of Rehabilitation at the University Hospital (FMRP-USP), Ribeirao Preto, Brazil. Methods: Eight individuals, four paraplegics and four tetraplegics with SCI and 20 healthy individuals participated in the study. Photos were taken of individuals in the sitting position using foam, gel cushions and with no cushion. They were analyzed using the PAS/SAPO. The alignment of the anterior-superior iliac spine (ASIS) and the posterior pelvic tilt were evaluated from the angle formed between the ASIS and the greater trochanter of the femur. Results: The group of healthy individuals presented the best postural alignment when compared with the group with SCI, both for the ASIS alignment (P < 0.05) and for the degree of posterior pelvic tilt (P < 0.05). No significant differences were found in the variables analyzed when the seat cushions were compared. Conclusion: The different types of cushions did not alter the sitting posture; however, individuals with SCI showed worse postural alignment than the healthy individuals. PAS/SAPO was demonstrated to be useful for postural assessment. Spinal Cord (2012) 50, 627-631; doi:10.1038/sc.2012.7; published online 21 February 2012

Therapeutic approaches for spinal cord injury

This study reviews the literature concerning possible therapeutic approaches for spinal cord injury. Spinal cord injury is a disabling and irreversible condition that has high economic and social costs. There are both primary and secondary mechanisms of damage to the spinal cord. The primary lesion is the mechanical injury itself. The secondary lesion results from one or more biochemical and cellular processes that are triggered by the primary lesion. The frustration of health professionals in treating a severe spinal cord injury was described in 1700 BC in an Egyptian surgical papyrus that was translated by Edwin Smith; the papyrus reported spinal fractures as a ''disease that should not be treated.'' Over the last biological or pharmacological treatment method. Science is unraveling the mechanisms of cell protection and neuroregeneration, but clinically, we only provide supportive care for patients with spinal cord injuries. By combining these treatments, researchers attempt to enhance the functional recovery of patients with spinal cord injuries. Advances in the last decade have allowed us to encourage the development of experimental studies in the field of spinal cord regeneration. The combination of several therapeutic strategies should, at minimum, allow for partial functional recoveries for these patients, which could improve their quality of life.

Technical innovations for the diagnosis and the rehabilitation of motor and perceptive impairments of the child with Cerebral Palsy

The treatment of the Cerebral Palsy (CP) is considered as the “core problem” for the whole field of the pediatric rehabilitation. The reason why this pathology has such a primary role, can be ascribed to two main aspects. First of all CP is the form of disability most frequent in childhood (one new case per 500 birth alive, (1)), secondarily the functional recovery of the “spastic” child is, historically, the clinical field in which the majority of the therapeutic methods and techniques (physiotherapy, orthotic, pharmacologic, orthopedic-surgical, neurosurgical) were first applied and tested. The currently accepted definition of CP – Group of disorders of the development of movement and posture causing activity limitation (2) – is the result of a recent update by the World Health Organization to the language of the International Classification of Functioning Disability and Health, from the original proposal of Ingram – A persistent but not unchangeable disorder of posture and movement – dated 1955 (3). This definition considers CP as a permanent ailment, i.e. a “fixed” condition, that however can be modified both functionally and structurally by means of child spontaneous evolution and treatments carried out during childhood. The lesion that causes the palsy, happens in a structurally immature brain in the pre-, peri- or post-birth period (but only during the firsts months of life). The most frequent causes of CP are: prematurity, insufficient cerebral perfusion, arterial haemorrhage, venous infarction, hypoxia caused by various origin (for example from the ingestion of amniotic liquid), malnutrition, infection and maternal or fetal poisoning. In addition to these causes, traumas and malformations have to be included. The lesion, whether focused or spread over the nervous system, impairs the whole functioning of the Central Nervous System (CNS). As a consequence, they affect the construction of the adaptive functions (4), first of all posture control, locomotion and manipulation. The palsy itself does not vary over time, however it assumes an unavoidable “evolutionary” feature when during growth the child is requested to meet new and different needs through the construction of new and different functions. It is essential to consider that clinically CP is not only a direct expression of structural impairment, that is of etiology, pathogenesis and lesion timing, but it is mainly the manifestation of the path followed by the CNS to “re”-construct the adaptive functions “despite” the presence of the damage. “Palsy” is “the form of the function that is implemented by an individual whose CNS has been damaged in order to satisfy the demands coming from the environment” (4). Therefore it is only possible to establish general relations between lesion site, nature and size, and palsy and recovery processes. It is quite common to observe that children with very similar neuroimaging can have very different clinical manifestations of CP and, on the other hand, children with very similar motor behaviors can have completely different lesion histories. A very clear example of this is represented by hemiplegic forms, which show bilateral hemispheric lesions in a high percentage of cases. The first section of this thesis is aimed at guiding the interpretation of CP. First of all the issue of the detection of the palsy is treated from historical viewpoint. Consequently, an extended analysis of the current definition of CP, as internationally accepted, is provided. The definition is then outlined in terms of a space dimension and then of a time dimension, hence it is highlighted where this definition is unacceptably lacking. The last part of the first section further stresses the importance of shifting from the traditional concept of CP as a palsy of development (defect analysis) towards the notion of development of palsy, i.e., as the product of the relationship that the individual however tries to dynamically build with the surrounding environment (resource semeiotics) starting and growing from a different availability of resources, needs, dreams, rights and duties (4). In the scientific and clinic community no common classification system of CP has so far been universally accepted. Besides, no standard operative method or technique have been acknowledged to effectively assess the different disabilities and impairments exhibited by children with CP. CP is still “an artificial concept, comprising several causes and clinical syndromes that have been grouped together for a convenience of management” (5). The lack of standard and common protocols able to effectively diagnose the palsy, and as a consequence to establish specific treatments and prognosis, is mainly because of the difficulty to elevate this field to a level based on scientific evidence. A solution aimed at overcoming the current incomplete treatment of CP children is represented by the clinical systematic adoption of objective tools able to measure motor defects and movement impairments. A widespread application of reliable instruments and techniques able to objectively evaluate both the form of the palsy (diagnosis) and the efficacy of the treatments provided (prognosis), constitutes a valuable method able to validate care protocols, establish the efficacy of classification systems and assess the validity of definitions. Since the ‘80s, instruments specifically oriented to the analysis of the human movement have been advantageously designed and applied in the context of CP with the aim of measuring motor deficits and, especially, gait deviations. The gait analysis (GA) technique has been increasingly used over the years to assess, analyze, classify, and support the process of clinical decisions making, allowing for a complete investigation of gait with an increased temporal and spatial resolution. GA has provided a basis for improving the outcome of surgical and nonsurgical treatments and for introducing a new modus operandi in the identification of defects and functional adaptations to the musculoskeletal disorders. Historically, the first laboratories set up for gait analysis developed their own protocol (set of procedures for data collection and for data reduction) independently, according to performances of the technologies available at that time. In particular, the stereophotogrammetric systems mainly based on optoelectronic technology, soon became a gold-standard for motion analysis. They have been successfully applied especially for scientific purposes. Nowadays the optoelectronic systems have significantly improved their performances in term of spatial and temporal resolution, however many laboratories continue to use the protocols designed on the technology available in the ‘70s and now out-of-date. Furthermore, these protocols are not coherent both for the biomechanical models and for the adopted collection procedures. In spite of these differences, GA data are shared, exchanged and interpreted irrespectively to the adopted protocol without a full awareness to what extent these protocols are compatible and comparable with each other. Following the extraordinary advances in computer science and electronics, new systems for GA no longer based on optoelectronic technology, are now becoming available. They are the Inertial and Magnetic Measurement Systems (IMMSs), based on miniature MEMS (Microelectromechanical systems) inertial sensor technology. These systems are cost effective, wearable and fully portable motion analysis systems, these features gives IMMSs the potential to be used both outside specialized laboratories and to consecutive collect series of tens of gait cycles. The recognition and selection of the most representative gait cycle is then easier and more reliable especially in CP children, considering their relevant gait cycle variability. The second section of this thesis is focused on GA. In particular, it is firstly aimed at examining the differences among five most representative GA protocols in order to assess the state of the art with respect to the inter-protocol variability. The design of a new protocol is then proposed and presented with the aim of achieving gait analysis on CP children by means of IMMS. The protocol, named ‘Outwalk’, contains original and innovative solutions oriented at obtaining joint kinematic with calibration procedures extremely comfortable for the patients. The results of a first in-vivo validation of Outwalk on healthy subjects are then provided. In particular, this study was carried out by comparing Outwalk used in combination with an IMMS with respect to a reference protocol and an optoelectronic system. In order to set a more accurate and precise comparison of the systems and the protocols, ad hoc methods were designed and an original formulation of the statistical parameter coefficient of multiple correlation was developed and effectively applied. On the basis of the experimental design proposed for the validation on healthy subjects, a first assessment of Outwalk, together with an IMMS, was also carried out on CP children. The third section of this thesis is dedicated to the treatment of walking in CP children. Commonly prescribed treatments in addressing gait abnormalities in CP children include physical therapy, surgery (orthopedic and rhizotomy), and orthoses. The orthotic approach is conservative, being reversible, and widespread in many therapeutic regimes. Orthoses are used to improve the gait of children with CP, by preventing deformities, controlling joint position, and offering an effective lever for the ankle joint. Orthoses are prescribed for the additional aims of increasing walking speed, improving stability, preventing stumbling, and decreasing muscular fatigue. The ankle-foot orthosis (AFO), with a rigid ankle, are primarily designed to prevent equinus and other foot deformities with a positive effect also on more proximal joints. However, AFOs prevent the natural excursion of the tibio-tarsic joint during the second rocker, hence hampering the natural leaning progression of the whole body under the effect of the inertia (6). A new modular (submalleolar) astragalus-calcanear orthosis, named OMAC, has recently been proposed with the intention of substituting the prescription of AFOs in those CP children exhibiting a flat and valgus-pronated foot. The aim of this section is thus to present the mechanical and technical features of the OMAC by means of an accurate description of the device. In particular, the integral document of the deposited Italian patent, is provided. A preliminary validation of OMAC with respect to AFO is also reported as resulted from an experimental campaign on diplegic CP children, during a three month period, aimed at quantitatively assessing the benefit provided by the two orthoses on walking and at qualitatively evaluating the changes in the quality of life and motor abilities. As already stated, CP is universally considered as a persistent but not unchangeable disorder of posture and movement. Conversely to this definition, some clinicians (4) have recently pointed out that movement disorders may be primarily caused by the presence of perceptive disorders, where perception is not merely the acquisition of sensory information, but an active process aimed at guiding the execution of movements through the integration of sensory information properly representing the state of one’s body and of the environment. Children with perceptive impairments show an overall fear of moving and the onset of strongly unnatural walking schemes directly caused by the presence of perceptive system disorders. The fourth section of the thesis thus deals with accurately defining the perceptive impairment exhibited by diplegic CP children. A detailed description of the clinical signs revealing the presence of the perceptive impairment, and a classification scheme of the clinical aspects of perceptual disorders is provided. In the end, a functional reaching test is proposed as an instrumental test able to disclosure the perceptive impairment. References 1. Prevalence and characteristics of children with cerebral palsy in Europe. Dev Med Child Neurol. 2002 Set;44(9):633-640. 2. Bax M, Goldstein M, Rosenbaum P, Leviton A, Paneth N, Dan B, et al. Proposed definition and classification of cerebral palsy, April 2005. Dev Med Child Neurol. 2005 Ago;47(8):571-576. 3. Ingram TT. A study of cerebral palsy in the childhood population of Edinburgh. Arch. Dis. Child. 1955 Apr;30(150):85-98. 4. Ferrari A, Cioni G. The spastic forms of cerebral palsy : a guide to the assessment of adaptive functions. Milan: Springer; 2009. 5. Olney SJ, Wright MJ. Cerebral Palsy. Campbell S et al. Physical Therapy for Children. 2nd Ed. Philadelphia: Saunders. 2000;:533-570. 6. Desloovere K, Molenaers G, Van Gestel L, Huenaerts C, Van Campenhout A, Callewaert B, et al. How can push-off be preserved during use of an ankle foot orthosis in children with hemiplegia? A prospective controlled study. Gait Posture. 2006 Ott;24(2):142-151.

Brain herniation in a patient with apparently normal intracranial pressure: a case report

Introduction Intracranial pressure monitoring is commonly implemented in patients with neurologic injury and at high risk of developing intracranial hypertension, to detect changes in intracranial pressure in a timely manner. This enables early and potentially life-saving treatment of intracranial hypertension. Case presentation An intraparenchymal pressure probe was placed in the hemisphere contralateral to a large basal ganglia hemorrhage in a 75-year-old Caucasian man who was mechanically ventilated and sedated because of depressed consciousness. Intracranial pressures were continuously recorded and never exceeded 17 mmHg. After sedation had been stopped, our patient showed clinical signs of transtentorial brain herniation, despite apparently normal intracranial pressures (less than 10 mmHg). Computed tomography revealed that the size of the intracerebral hematoma had increased together with significant unilateral brain edema and transtentorial herniation. The contralateral hemisphere where the intraparenchymal pressure probe was placed appeared normal. Our patient underwent emergency decompressive craniotomy and was tracheotomized early, but did not completely recover. Conclusions Intraparenchymal pressure probes placed in the hemisphere contralateral to an intracerebral hematoma may dramatically underestimate intracranial pressure despite apparently normal values, even in the case of transtentorial brain herniation.

Virtopsy: CT and MR imaging of a fatal head injury caused by a hatchet: A case report

Hatchet blows to the human skull often cause fatal injuries. We present a case of homicide by hatchet blow that underwent CT, MRI, and autopsy examination. Skull fragmentation, fracture lines, and brain injuries were demonstrated prior to autopsy. Many of the hatchet-specific characteristics (flaking, crushing, shattering, and fracture lines) described in literature were observed in the post-mortem imaging of this case.

The sense of the body in individuals with spinal cord injury

Increasing evidence suggests that the basic foundations of the self lie in the brain systems that represent the body. Specific sensorimotor stimulation has been shown to alter the bodily self. However, little is known about how disconnection of the brain from the body affects the phenomenological sense of the body and the self. Spinal cord injury (SCI) patients who exhibit massively reduced somatomotor processes below the lesion in the absence of brain damage are suitable for testing the influence of body signals on two important components of the self-the sense of disembodiment and body ownership. We recruited 30 SCI patients and 16 healthy participants, and evaluated the following parameters: (i) depersonalization symptoms, using the Cambridge Depersonalization Scale (CDS), and (ii) measures of body ownership, as quantified by the rubber hand illusion (RHI) paradigm. We found higher CDS scores in SCI patients, which show increased detachment from their body and internal bodily sensations and decreasing global body ownership with higher lesion level. The RHI paradigm reveals no alterations in the illusory ownership of the hand between SCI patients and controls. Yet, there was no typical proprioceptive drift in SCI patients with intact tactile sensation on the hand, which might be related to cortical reorganization in these patients. These results suggest that disconnection of somatomotor inputs to the brain due to spinal cord lesions resulted in a disturbed sense of an embodied self. Furthermore, plasticity-related cortical changes might influence the dynamics of the bodily self.

Effect of a lung recruitment maneuver by high-frequency oscillatory ventilation in experimental acute lung injury on organ blood flow in pigs

INTRODUCTION: The objective was to study the effects of a lung recruitment procedure by stepwise increases of mean airway pressure upon organ blood flow and hemodynamics during high-frequency oscillatory ventilation (HFOV) versus pressure-controlled ventilation (PCV) in experimental lung injury. METHODS: Lung damage was induced by repeated lung lavages in seven anesthetized pigs (23-26 kg). In randomized order, HFOV and PCV were performed with a fixed sequence of mean airway pressure increases (20, 25, and 30 mbar every 30 minutes). The transpulmonary pressure, systemic hemodynamics, intracranial pressure, cerebral perfusion pressure, organ blood flow (fluorescent microspheres), arterial and mixed venous blood gases, and calculated pulmonary shunt were determined at each mean airway pressure setting. RESULTS: The transpulmonary pressure increased during lung recruitment (HFOV, from 15 +/- 3 mbar to 22 +/- 2 mbar, P < 0.05; PCV, from 15 +/- 3 mbar to 23 +/- 2 mbar, P < 0.05), and high airway pressures resulted in elevated left ventricular end-diastolic pressure (HFOV, from 3 +/- 1 mmHg to 6 +/- 3 mmHg, P < 0.05; PCV, from 2 +/- 1 mmHg to 7 +/- 3 mmHg, P < 0.05), pulmonary artery occlusion pressure (HFOV, from 12 +/- 2 mmHg to 16 +/- 2 mmHg, P < 0.05; PCV, from 13 +/- 2 mmHg to 15 +/- 2 mmHg, P < 0.05), and intracranial pressure (HFOV, from 14 +/- 2 mmHg to 16 +/- 2 mmHg, P < 0.05; PCV, from 15 +/- 3 mmHg to 17 +/- 2 mmHg, P < 0.05). Simultaneously, the mean arterial pressure (HFOV, from 89 +/- 7 mmHg to 79 +/- 9 mmHg, P < 0.05; PCV, from 91 +/- 8 mmHg to 81 +/- 8 mmHg, P < 0.05), cardiac output (HFOV, from 3.9 +/- 0.4 l/minute to 3.5 +/- 0.3 l/minute, P < 0.05; PCV, from 3.8 +/- 0.6 l/minute to 3.4 +/- 0.3 l/minute, P < 0.05), and stroke volume (HFOV, from 32 +/- 7 ml to 28 +/- 5 ml, P < 0.05; PCV, from 31 +/- 2 ml to 26 +/- 4 ml, P < 0.05) decreased. Blood flows to the heart, brain, kidneys and jejunum were maintained. Oxygenation improved and the pulmonary shunt fraction decreased below 10% (HFOV, P < 0.05; PCV, P < 0.05). We detected no differences between HFOV and PCV at comparable transpulmonary pressures. CONCLUSION: A typical recruitment procedure at the initiation of HFOV improved oxygenation but also decreased systemic hemodynamics at high transpulmonary pressures when no changes of vasoactive drugs and fluid management were performed. Blood flow to the organs was not affected during lung recruitment. These effects were independent of the ventilator mode applied.

Hypoxic preconditioning reverses protection after neonatal hypoxia-ischemia in glutathione peroxidase transgenic murine brain

The effect of hypoxic preconditioning (PC) on hypoxic-ischemic (HI) injury was explored in glutathione peroxidase (GPx)-overexpressing mice (human GPx-transgenic [hGPx-tg]) mice. Six-day-old hGPx-tg mice and wild-type (Wt) littermates were pre-conditioned with hypoxia for 30 min and subjected to the Vannucci procedure of HI 24 h after the PC stimulus. Histopathological injury was determined 5 d later (P12). Additional animals were killed 2 h or 24 h after HI and ipsilateral cerebral cortices assayed for GPx activity, glutathione (GSH), and hydrogen peroxide (H2O2). In line with previous studies, hypoxic PC reduced injury in the Wt brain. Preconditioned Wt brain had increased GPx activity, but reduced GSH, relative to naive 24 h after HI. Hypoxic PC did not reduce injury to hGPx-tg brain and even reversed the protection previously reported in the hGPx-tg. GPx activity and GSH in hGPx-tg cortices did not change. Without PC, hGPx-tg cortex had less H2O2 accumulation than Wt at both 2 h and 24 h. With PC, H2O2 remained low in hGPx-tg compared with Wt at 2 h, but at 24 h, there was no longer a difference between hGPx-tg and Wt cortices. Accumulation of H2O2 may be a mediator of injury, but may also induce protective mechanisms.

Online correlation of spontaneous arterial and intracranial pressure fluctuations in patients with diffuse severe head injury

Determination of relevant clinical monitoring parameters for helping guide the intensive care therapy in patients with severe head injury, is one of the most demanding issues in neurotrauma research. New insights into cerebral autoregulation and metabolism have revealed that a rigid cerebral perfusion pressure (CPP) regimen might not be suitable for all severe head injured patients. We thus developed an online analysis technique to monitor the correlation (AI rho) between the spontaneous fluctuations of the mean arterial blood pressure (MABP) and the intracranial pressure (ICP). In addition, brain tissue oxygen (PtiO2) and metabolic microdialysate measures including glucose and lactate were registered. We found that in patients with good outcome, the AI rho values were significantly lower as compared with patients with poor outcome. Accordingly, microdialysate glucose and lactate were significantly higher in the good outcome group. We conclude that online determination of AI rho offers a valuable additional and technically easily performable tool for guidance of therapy in patients with severe head injury.

Multiple pathways of neuroprotection against oxidative stress and excitotoxic injury in immature primary hippocampal neurons

In the immature brain hydrogen peroxide accumulates after excitotoxic hypoxia-ischemia and is neurotoxic. Immature hippocampal neurons were exposed to N-methyl-D-aspartate (NMDA), a glutamate agonist, and hydrogen peroxide (H(2)O(2)) and the effects of free radical scavenging and transition metal chelation on neurotoxicity were studied. alpha-Phenyl-N-tert.-butylnitrone (PBN), a known superoxide scavenger, attenuated both H(2)O(2) and NMDA mediated toxicity. Treatment with desferrioxamine (DFX), an iron chelator, at the time of exposure to H(2)O(2) was ineffective, but pretreatment was protective. DFX also protected against NMDA toxicity. TPEN, a metal chelator with higher affinities for a broad spectrum of transition metal ions, also protected against H(2)O(2) toxicity but was ineffective against NMDA induced toxicity. These data suggest that during exposure to free radical and glutamate agonists, the presence of iron and other free metal ions contribute to neuronal cell death. In the immature nervous system this neuronal injury can be attenuated by free radical scavengers and metal chelators.