Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie
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Exp. Toxicol. Pathol. · Jul 2005
ReviewBiomonitoring of inhaled complex mixtures--ambient air, diesel exhaust and cigarette smoke.
Human biomonitoring comprises the determination of biomarkers in body-fluids, cells and tissues. Biomarkers are generally assigned to one of three classes, namely, biomarkers of exposure, effect or susceptibility. Since biomarkers represent steps in an exposure-disease continuum, their application in epidemiological studies ('molecular epidemiology') shows promise. ⋯ Finally, suitable study designs for evaluating PREPs are discussed. It is concluded that suitable biomarkers for assessing the exposure to complex mixtures such as ambient air, diesel exhaust and tobacco smoke as well as for evaluating the exposure-reducing properties of PREPs are already available. Future efforts should focus on the development and validation of biomarkers of effect.
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Exp. Toxicol. Pathol. · Mar 2005
Role of adhesion molecule ICAM in the pathogenesis of polymicrobial sepsis.
Intercellular adhesion molecule-1 (ICAM-1) is thought to be involved in polymorphonuclear leukocytes (PMNL) recruitment and secondary organ damage in response to infection and inflammation. The precise role of ICAM-1 in disease progression is unknown and remains a topic of controversy. The aim of this study was to investigate the effect of ICAM-1 on histological changes and cytokine synthesis in a murine model of polymicrobial sepsis. ⋯ This study suggests that ICAM-1 has an important pathophysiological role in the response to polymicrobial sepsis. It would appear that absence of this molecule impairs the ability of PMNL to migrate into organ tissues and reduces consequent secondary organ damage resulting in improved clinical status and overall survival. Further investigation into the effectiveness of ICAM-1 modulation in the treatment of sepsis is warranted.
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Traumatic brain injury (TBI) is the leading cause of death in childhood; however only very few studies focusing on the specific pathophysiology and treatment have been published to date. Head trauma is more likely in young children than in adults given the same deceleration of the body due to their large and heavy heads and weak cervical ligaments and muscles. Resulting brain injury is more severe due to their thin, pliable skulls and the yet unfused sutures. ⋯ For several other therapeutical means, e.g. hypothermia or specific surgical interventions, clinical evidence to date is insufficient to allow recommendation as rescue treatment for children at risk of severe neurological sequelae following TBI. This review discusses the clinical implication of pathophysiologic mechanisms of TBI in the developing brain according to the recent literature and current guidelines. It follows the clinical approach to a head injured child, that can be divided into three phases, i.e. initial assessment and stabilization, followed by first tier, and if necessary second tier therapeutic interventions to assure adequate oxygenation and perfusion of the brain.
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Exp. Toxicol. Pathol. · Oct 2004
ReviewTraumatic injury in the developing brain--effects of hypothermia.
Little is known about the underlying mechanisms of head trauma in the developing brains, despite considerable social and economic impact following such injuries. Age has been shown to substantially influence morbidity and mortality. Children younger than 4 years of age had worse cognitive, motor, and brain atrophy outcomes than children 6 years of age and older. ⋯ As an alternative/ adjunct to pharmacological approaches, hypothermia has been shown to be cerebroprotective in traumatized adult brains. Although a large number of animal studies have shown protective effects of hypothermia in a variety of damaging mechanisms after TBI, little data exist for young, developing brains. The injury mechanisms of TBI in the immature, effects of hypothermia following resuscitation on adult and immature traumatized brains, and some possible mechanisms of action of hypothermia in the immature traumatized brain are discussed in this review.
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Exp. Toxicol. Pathol. · Jun 2003
Monitoring of a single post-infusion blood sample to estimate the actual peak and trough concentration of tobramycin in critically ill patients.
The therapy of critically ill patients with aminoglycoside antibiotics requires a careful dosing to achieve effective drug concentrations and to avoid toxic effects. ⋯ In the critically ill, C3h but not C8h of tobramycin permitted the estimation of the Cpeak30 in most cases with satisfactory bias and precision starting with 2nd monitored dosing interval. However, high trough levels requiring an adjustment of dose or dosing interval could not be safely predicted; prediction error was intolerable when C22h exceeded the target range of trough level. Data indicate that at least in patients with any sign of renal dysfunction, the measuring of the interesting levels should be preferred to the tested single-point based estimations.