ABSTRACT
Current approaches to monitoring in severe traumatic brain injury (TBI) include a wide array of modalities, providing insight into pressure parameters, oxygenation, perfusion, electrophysiology and metabolism of the brain. The intent of "multimodality monitoring" is to obtain a better understanding of what is going on within the brain of an individual patient in order to target treatment more appropriately. In this review we highlight the current status of neuromonitoring for TBI with a specific focus on how advanced analysis and integration of these parameters may be used to implement more personalized treatment approaches. In particular, combining information from different parameters and performing dynamic testing offers the potential to better understand the pathophysiological mechanisms active in the brain of a particular patient. Rather than persisting in a standardized "one size fits all" approach to therapy or continuing down the separate tracts of goal directed therapy, we suggest to think more in terms of "individualized therapeutic strategies" more focused on the specific requirements of each patient. Given the considerable data overload in multimodality monitoring and the complexity in interpretation of signals from multiple sources, specific attention needs to be directed to data processing and user-friendly displays. Intense collaboration and interaction between clinicians, basic researchers, IT-experts, nurses and industry will be required to further advance the fields towards more personalized approaches.
Subject(s)
Brain Injuries/physiopathology , Monitoring, Physiologic/methods , Brain Chemistry , Cerebrovascular Circulation , Critical Care , Electroencephalography , Homeostasis , Humans , Intracranial Pressure , Oxygen Consumption , Precision MedicineABSTRACT
Unscheduled mortality preceded by adverse respiratory clinical signs in rats dosed by oral gavage may not only be caused by technical gavage error or systemic toxicity but may also be caused by gastro-esophageal reflux and subsequent aspiration of high concentrations of drug formulation. In a 3 week oral gavage rat toxicity study for an early drug development compound, preterminal deaths (approximately 20% of animals) at high doses (≥1000 mg kg(-1) ) and concentrations (≥60 mg ml(-1) ) were preceded by recurrent dyspnea, rales or excessive salivation, without evidence of accidental intrapulmonary gavage error. Histological evaluation revealed extensive necrosis and inflammatory changes in the upper respiratory tract, especially in the nasal turbinates and/or nasopharynx. The presence of food particles in inflammatory exudates suggested a retrograde aspiration of stomach content with test formulation via the nasopharyngeal duct into the posterior region of the nose. In contrast, no mortality or adverse respiratory effects were observed in rats following 2 week intravenous administration at comparable exposures or oral gavage administration at lower concentrations (≤20 mg ml(-1) ). In a pharmacology study, the compound caused a dose-dependent increase in gastric content (partly due to inhibition of gastric emptying), providing a pharmacological basis for the suspected gavage-mediated gastroesophageal reflux. Reducing the dose volume and dosing fasted animals substantially reduced or eliminated the respiratory effects and mortality at the high test article concentrations, demonstrating that the adverse effects are related to the gavage method.
Subject(s)
Dyspnea/etiology , Gastroesophageal Reflux/etiology , Gastrointestinal Contents , Intubation, Gastrointestinal/adverse effects , Respiratory Aspiration/etiology , Toxicity Tests/methods , Administration, Oral , Animals , Female , Injections, Intravenous , Intubation, Gastrointestinal/methods , Male , Pharmaceutical Preparations/administration & dosage , Rats , Rats, Sprague-Dawley , Rats, Wistar , Toxicity Tests/standardsABSTRACT
BACKGROUND: Collagenous colitis is typified by chronic watery diarrhoea and characteristic histological alterations of the colonic mucosa without endoscopic abnormalities. Budesonide, a corticosteroid with high first-pass metabolism has been examined in collagenous colitis, but studies to date have had small numbers, and relatively low statistical power. AIM: A meta-analysis of existing published trials was undertaken to evaluate the treatment effect of budesonide in collagenous colitis. METHODS: All pertinent literature sources were searched for published reports in English of budesonide use in collagenous colitis. MEDLINE and EMBASE databases were reviewed, as well as bibliographies from published articles and available abstracts from relevant meetings. Literature that met prespecified criteria was selected for the meta-analysis. RESULTS: Three trials were included in the meta-analysis. Budesonide significantly decreased stool frequency (budesonide vs. placebo OR: 20.1, 95% CI: 7.0-57.5, P < 0.0001). In general, budesonide treatment was well-tolerated. CONCLUSIONS: Budesonide is clinically effective short-term in collagenous colitis, and seems to be relatively well-tolerated. Clinicians can consider this drug as a reasonable option for patients with this disorder.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Budesonide/therapeutic use , Colitis, Collagenous/drug therapy , Drug Evaluation , Humans , Randomized Controlled Trials as Topic , Risk FactorsABSTRACT
Mannheimia varigena was identified as the etiologic agent of meningitis in a young Belgian White Blue heifer calf. Species identification of the bacterium was done by phenotyping and molecularly confirmed by tDNA-PCR. Standard bacteriological examination might fail to differentiate species belonging to the genus Mannheimia.
