Shinya Tsuchida

RATIONALE: Many authors have suggested that the mechanism by which atelectasis contributes to injury is through the repetitive opening and closing of distal airways in lung regions that are atelectatic. However, neither the topographic nor mechanistic relationships between atelectasis and distribution of lung injury are known. OBJECTIVES: To investigate how atelectasis contributes to ventilator-induced lung injury. METHODS: Surfactant depletion was performed in anesthetized rats that were then allocated to noninjurious or injurious ventilation for 90 min. MEASUREMENTS: Lung injury was quantified by gas exchange, compliance, histology, wet-to-dry weight, and cytokine expression, and its distribution by histology, stereology, cytokine mRNA expression, in situ hybridization, and immunohistochemistry. Functional residual capacity, percent atelectasis, and injury-induced lung water accumulation were measured using gravimetric and volumetric techniques. MAIN RESULTS: Atelectasis occurred in the dependent lung regions. Injurious ventilation was associated with alveolar and distal airway injury, while noninjurious ventilation was not. With injurious ventilation, alveolar injury (i.e., histology, myeloperoxidase protein expression, quantification, and localization of cytokine mRNA expression) was maximal in nondependent regions, whereas distal airway injury was equivalent in atelectatic and nonatelectatic regions. CONCLUSIONS: These data support the notion that lung injury associated with atelectasis involves trauma to the distal airways. We provide topographic and biochemical evidence that such distal airway injury is not localized solely to atelectatic areas, but is instead generalized in both atelectatic and nonatelectatic lung regions. In contrast, alveolar injury associated with atelectasis does not occur in those areas that are atelectatic but occurs instead in remote nonatelectatic alveoli.

RATIONALE: Ventilator-induced lung injury has been predominantly studied in adults. OBJECTIVES: To explore the effects of age and lung development on susceptibility to such injury. METHODS: Ex vivo isolated nonperfused rat lungs (infant, juvenile, and adult) were mechanically ventilated where VT was based on milliliters per kilogram of body weight or as a percentage of the measured total lung capacity (TLC). In vivo anesthetized rats (infant, adult) were mechanically ventilated with pressure-limited VTs. Allocation to ventilation strategy was randomized. MEASUREMENTS: Ex vivo injury was assessed by pressure-volume analysis, reduction in TLC, and histology, and in vivo injury by lung compliance, cytokine production, and wet- to dry-weight ratio. MAIN RESULTS: Ex vivo ventilation (VT 30 ml.kg(-1)) resulted in a significant reduction (36.0 +/- 10.1%, p < 0.05) in TLC in adult but not in infant lungs. Ex vivo ventilation (VT 50% TLC) resulted in a significant reduction in TLC in both adult (27.8 +/- 2.8%) and infant (10.6 +/- 7.0%) lungs, but more so in the adult lungs (p < 0.05); these changes were paralleled by histology and pressure-volume characteristics. After high stretch in vivo ventilation, adult but not infant rats developed lung injury (total lung compliance, wet/dry ratio, tumor necrosis factor alpha). Surface video microscopy demonstrated greater heterogeneity of alveolar distension in ex vivo adult versus infant lungs. CONCLUSION: These data provide ex vivo and in vivo evidence that comparable ventilator settings are significantly more injurious in the adult than infant rat lung, probably reflecting differences in intrinsic susceptibility or inflation pattern.

Idiopathic low-molecular-weight (LMW) proteinuria is a newly described renal disease in Japan and Italy. We report on 7 patients who manifested bilateral or unilateral nephrocalcinosis, as demonstrated by abdominal computed tomography scans. Renal histology revealed calcinosis of renal tubules in 2 patients. Computed tomography is a reliable method for the detection of nephrocalcinosis in this disorder. Hypercalciuria was also seen in 6 patients. A calcium-loading test performed in 2 patients suggested that hypercalciuria was of renal origin. Although the true pathogenesis is still not known, hypercalciuria and nephrocalcinosis appear to be a common complication in patients with idiopathic LMW proteinuria. These complications and clinical features suggest that idiopathic LMW proteinuria in Japan is likely to be identical to Dent's disease in the United Kingdom.

A crucial issue in neonatal medicine is the impact of preterm birth on the developmental trajectory of the brain. Although a growing number of studies have shown alterations in the structure and function of the brain in preterm-born infants, we propose a method to detect subtle differences in neurovascular and metabolic functions in neonates and infants. Functional near-infrared spectroscopy (fNIRS) was used to obtain time-averaged phase differences between spontaneous low-frequency (less than 0.1 Hz) oscillatory changes in oxygenated hemoglobin (oxy-Hb) and those in deoxygenated hemoglobin (deoxy-Hb). This phase difference was referred to as hemoglobin phase of oxygenation and deoxygenation (hPod) in the cerebral tissue of sleeping neonates and infants. We examined hPod in term, late preterm, and early preterm infants with no evidence of clinical issues and found that all groups of infants showed developmental changes in the values of hPod from an in-phase to an antiphase pattern. Comparison of hPod among the groups revealed that developmental changes in hPod in early preterm infants precede those in late preterm and term infants at term equivalent age but then, progress at a slower pace. This study suggests that hPod measured using fNIRS is sensitive to the developmental stage of the integration of circular, neurovascular, and metabolic functions in the brains of neonates and infants.