Combination effects of azole fungicides in male rats in a broad dose range.

Two 28-day feeding studies were performed in male rats to investigate combination effects of azole fungicides in a broad dose range. Following separate administration of cyproconazole, epoxiconazole, prochloraz, propiconazole, and tebuconazole at five dose levels, the first three compounds were selected to be administered in two different mixtures at three dose levels including very low doses. Here we present the data obtained by clinical observations, pathology, histopathology, clinical chemistry and haematology. The liver was the common main target organ of all compounds and their mixtures. In addition, epoxiconazole exhibited an effect on the adrenals. Furthermore, food consumption and efficiency and body weight (gain) were affected. Adverse effects of the combinations were observed at dose levels at which the individual substances caused similar effects. No evidence of adverse effects was found at dose levels below the previously established NOAELs. Our findings indicate that the concept of dose additivity appears sufficiently protective for risk assessment of the fungicides examined. Besides toxicological testing, tissue residues of the azole compounds in liver, testis and kidney were determined revealing remarkable differences following administration of the single substances and of the mixtures.

How bold is blood oxygenation level-dependent (BOLD) magnetic resonance imaging of the kidney? Opportunities, challenges and future directions.

Renal tissue hypoperfusion and hypoxia are key elements in the pathophysiology of acute kidney injury and its progression to chronic kidney disease. Yet, in vivo assessment of renal haemodynamics and tissue oxygenation remains a challenge. Many of the established approaches are invasive, hence not applicable in humans. Blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) offers an alternative. BOLD-MRI is non-invasive and indicative of renal tissue oxygenation. Nonetheless, recent (pre-) clinical studies revived the question as to how bold renal BOLD-MRI really is. This review aimed to deliver some answers. It is designed to inspire the renal physiology, nephrology and imaging communities to foster explorations into the assessment of renal oxygenation and haemodynamics by exploiting the powers of MRI. For this purpose, the specifics of renal oxygenation and perfusion are outlined. The fundamentals of BOLD-MRI are summarized. The link between tissue oxygenation and the oxygenation-sensitive MR biomarker T2∗ is outlined. The merits and limitations of renal BOLD-MRI in animal and human studies are surveyed together with their clinical implications. Explorations into detailing the relation between renal T2∗ and renal tissue partial pressure of oxygen (pO2 ) are discussed with a focus on factors confounding the T2∗ vs. tissue pO2 relation. Multi-modality in vivo approaches suitable for detailing the role of the confounding factors that govern T2∗ are considered. A schematic approach describing the link between renal perfusion, oxygenation, tissue compartments and renal T2∗ is proposed. Future directions of MRI assessment of renal oxygenation and perfusion are explored.

Early effects of an x-ray contrast medium on renal T(2) */T(2) MRI as compared to short-term hyperoxia, hypoxia and aortic occlusion in rats.

AIM: X-ray contrast media (CM) can cause acute kidney injury (AKI). Medullary hypoxia is pivotal in CM-induced AKI, as indicated by invasively and pin-point measured tissue oxygenation. MRI provides spatially resolved blood oxygenation level-dependent data using T2 * and T2 mapping. We studied CM effects on renal T2 */T2 and benchmarked them against short periods of hyperoxia, hypoxia and aortic occlusion (AO). METHODS: Rats were equipped with carotid artery catheters (tip towards aorta) and supra-renal aortic occluders. T2 */T2 mapping was performed using a 9.4-T animal scanner. CM (1.5 mL iodixanol) was injected into the thoracic aorta with the animal in the scanner followed by 2 h of T2 */T2 mapping. For T2 */T2 assessment, regions of interest in the cortex (C), outer medulla (OM), inner medulla (IM) and papilla (P) were determined according to morphological features. RESULTS: Hyperoxia increased T2 * in C (by 17%) and all medullary layers (25-35%). Hypoxia decreased T2 * in C (40%) and all medullary layers (55-60%). AO decreased T2 * in C (18%) and all medullary layers (30-40%). Upon injection of CM, T2 * increased transiently, then decreased, reaching values 10-20% below baseline in C and OM and 30-40% below baseline in IM and P. CONCLUSION: T2 * mapping corroborates data previously obtained with invasive methods and demonstrates that CM injection affects renal medullary oxygenation. CM-induced T2 * decrease in OM was small vs. hypoxia and aortic occlusion. T2 * decrease obtained for hypoxia was more pronounced than for AO. This indicates that T2 * may not accurately reflect blood oxygenation under certain conditions.

Linking non-invasive parametric MRI with invasive physiological measurements (MR-PHYSIOL): towards a hybrid and integrated approach for investigation of acute kidney injury in rats.

Acute kidney injury of various origins shares a common link in the pathophysiological chain of events: imbalance between renal medullary oxygen delivery and oxygen demand. For in vivo assessment of kidney haemodynamics and oxygenation in animals, quantitative but invasive physiological methods are established. A very limited number of studies attempted to link these invasive methods with parametric Magnetic Resonance Imaging (MRI) of the kidney. Moreover, the validity of parametric MRI (pMRI) as a surrogate marker for renal tissue perfusion and renal oxygenation has not been systematically examined yet. For this reason, we set out to combine invasive techniques and non-invasive MRI in an integrated hybrid setup (MR-PHYSIOL) with the ultimate goal to calibrate, monitor and interpret parametric MR and physiological parameters by means of standardized interventions. Here we present a first report on the current status of this multi-modality approach. For this purpose, we first highlight key characteristics of renal perfusion and oxygenation. Second, concepts for in vivo characterization of renal perfusion and oxygenation are surveyed together with the capabilities of MRI for probing blood oxygenation-dependent tissue stages. Practical concerns evoked by the use of strong magnetic fields in MRI and interferences between MRI and invasive physiological probes are discussed. Technical solutions that balance the needs of in vivo physiological measurements together with the constraints dictated by small bore MR scanners are presented. An early implementation of the integrated MR-PHYSIOL approach is demonstrated including brief interventions of hypoxia and hyperoxia.

[Out-of-hospital cardiac arrest in children with bacterial tracheitis]. / Laryngotrachéites bactériennes révélées par un arrêt cardiaque en préhospitalier.

UNLABELLED: Bacterial tracheitis is a severe cause of acute infectious upper-airway obstruction. Its characteristics include thick purulent secretions with or without plaques or pseudomembrane formation. Fatal complications are infrequent if an appropriate treatment is conducted. CASE REPORT: We report on 2 cases of bacterial tracheitis revealed by out-of-hospital cardiac arrest. At presentation in winter, both children first had the symptoms of viral croup. However, no response to the appropriate therapy for this disease was observed. A cardiac arrest occurred on the second day. Bronchoscopy allowed diagnosis. Findings on initial examination were erythema, edema and purulent secretions. Bacterial cultures of tracheal secretions were positive with Staphylococcus aureus. Serology with influenza A virus was also positive. Despite antibiotics and mechanical ventilation, both children died in the pediatric intensive care unit, consecutively to irreversible ischemic brain injury. CONCLUSION: Bacterial tracheitis remains a life-threatening upper-airway infection. Prompt recognition and accurate diagnosis could lead to decreased mortality. It is essential to reassess any croup whose outcome is not rapidly favourable. Such patients should be monitored in a pediatric intensive care unit.

[Misleading diagnosis of a migratory epigastric pain in mobile emergency units: spontaneous rupture of the oesophagus]. / Diagnostic trompeur d'une douleur épigastrique migratrice en préhospitalier: la rupture spontanée de l'oesophage.

The local mobile emergency unit took charge of a patient who suffered from a sudden migratory epigastric pain in the back. The clinical picture led to an initial diagnosis of an aorta dissection. Admitted to Grenoble UH's emergency unit, the radiological examination ruled out a cardiovascular pathology. Emergency surgery, performed only a few hours after the symptoms began, allowed to correctly diagnose a spontaneous rupture of the oesophagus. Fast and specialised medical treatment avoided the risk of an unfavourable development of the Boerhaave's syndrome. It is essential that mobile emergency units personnel are made aware of this rare pathology, even though it remains particularly difficult to diagnose due to its rather non-specific symptoms.

[Epidemiological analysis of drug self-poisonings treated by a mobile intensive care unit]. / Analyse epidémiologique des intoxications médicamenteuses volontaires aiguës: prise en charge par un service mobile d'urgence et de réanimation.

PURPOSE: Study the epidemiology, prehospital emergency care and short-term evolution of the drug self poisonings. METHODS: Retrospective analysis from January 1999 to December 2000 of drug self poisonings requiring Grenoble (France) intensive care unit action and patient follow up. RESULTS: 325 patients, 39.3 years old +/- 14.5 have been treated. The drug self poisonings are representing 4.6% of Grenoble mobile intensive care unit activity. The sex-ratio was, for the 15 to 24 years old population, 2.3 females for 1 male. Mobile intensive care unit has been decided in first intention on 56.3%. 556 toxic substances have been reported, psychotropics are prevailing (79.4% of all drug self poisonings). Intubation has been necessary in 24%. 64.4% of the treated population has been hospitalized into intensive care units. The main exit step of the first admission unit was returning home. Death rate was 0.9%. CONCLUSION: Drug self poisoning is an important part of mobile intensive care unit activity. The very low death rate could be related to several criteria: a high efficient rescue unit setting up a symptomatic based medical treatment and the current decreased toxicity of the ingested drugs.

Measurement of beta-agonist residues in retinal tissue of food producing animals.

This report presents the results of an investigation on the accumulation of beta-agonist residues in the retinal tissue of food producing animals. Three different species, calf, pig and turkey, were treated with six different beta-agonists and analysed for beta-agonist residues in retinal tissue applying a newly developed retina preparation procedure which provides sufficient sample material for multiple analyses. The results show that all selected beta-agonists accumulate in the retina, though in varying concentrations. The results are discussed on the basis of existing binding theories and with regard to their impact on the existing residue control strategy for beta-agonists.