Lung hyperinflation and its reversibility in patients with airway obstruction of varying severity

The natural history of lung hyperinflation in patients with airway obstruction is unknown. In particular, little information exists about the extent of air trapping and its reversibility to bronchodilator therapy in those with mild airway obstruction. We completed a retrospective analysis of data from individuals with airway obstruction who attended our pulmonary function laboratory and had plethysmographic lung volume measurements pre- and post-bronchodilator (salbutamol). COPD was likely the predominant diagnosis but patients with asthma may have been included. We studied 2,265 subjects (61% male), age 65 ± 9 years (mean ± SD) with a post-bronchodilator FEV(1)/FVC <0.70. We examined relationships between indices of airway obstruction and lung hyperinflation, and measured responses to bronchodilation across subgroups stratified by GOLD criteria. In GOLD stage I, vital capacity (VC) and inspiratory capacity (IC) were in the normal range; pre-bronchodilator residual volume (RV), functional residual capacity (FRC) and specific airway resistance were increased to 135%, 119% and 250% of predicted, respectively. For the group as a whole, RV and FRC increased exponentially as FEV(1) decreased, while VC and IC decreased linearly. Regardless of baseline FEV(1), the most consistent improvement following bronchodilation was RV reduction, in terms of magnitude and responder rate. In conclusion, increases (above normal) in airway resistance and plethysmographic lung volumes were found in those with only minor airway obstruction. Indices of lung hyperinflation increased exponentially as airway obstruction worsened. Those with the greatest resting lung hyperinflation showed the largest bronchodilator-induced volume deflation effects. Reduced air trapping was the predominant response to acute bronchodilation across severity subgroups.     

The 4S polycyclic aromatic hydrocarbon-binding protein: immunohistochemical localization in mice

The 4S polycyclic aromatic hydrocarbon (PAH)-binding protein (PBP) is a cytoplasmic protein that binds PAHs with specificity and high affinity. We have used antisera for the PBP and unlabeled peroxidase anti-peroxidase immunohistochemistry to demonstrate its possible localization in cell types known to have xenobiotic metabolizing capabilities. Cellular sites of the PBP in liver, lung and kidney of C57BL/6 and DBA/2 mice were probed. The PBP was visualized in hepatocytes throughout the liver lobule and was not preferentially located in either centrilobular or periportal areas. However, cellular heterogeneity with respect to PBP content was clearly evident in the hepatocyte population. The positive reactivity correlated with substantial levels of benzo[a]pyrene (B[a]P) binding in liver cytosol. In the lung, the PBP was found in the bronchiolar epithelium and the alveolar septa, and was localized in ciliated and non-ciliated Clara and alveolar type II cells as well as in alveolar macrophages. In the kidney, the glomeruli and epithelia of proximal and distal convoluted tubules and collecting ducts were labeled. Staining for the PBP was greatest in the apical region of the pyramid and was localized in the epithelial lining of the collecting ducts. Relatively lower levels of the PBP were detected in the lung and kidney than in the liver. Staining was localized in the cytoplasmic compartment of cells in all tissues examined. Similar immunoreactivities were exhibited in the tissues of both C57BL/6 and DBA/2 mice. Treatment with beta-naphthoflavone (beta NF) altered neither the intensity nor pattern of immunostaining. Furthermore, treatment with beta NF or isosafrole has no effect on the Kd and Bmax of B[a]P binding to liver cytosolic PBP. The results of our experiments demonstrate localization of the PBP to sites of active physiological response to PAH exposure.     

Airway injury by trichloroethylene: a scanning electron microscopic study

We examined the effects of trichloroethylene (TCE) on the bronchiolar epithelium of mouse lung, using scanning electron microscopy. The lesion elicited by TCE involved predominantly the nonciliated Clara cells of the bronchiolar epithelium. Although there was slight loss of cilia and the mucosal surface exhibited increased deposits of debris throughout the period the tissues were observed, the ciliated cells appeared relatively uninjured. At 24 h following the intraperitoneal administration of TCE (2000 mg/kg) the Clara cells of the bronchiolar epithelium were irregularly distributed on the mucosal surface and reduced in number, indicating loss of cells by exfoliation. The remaining Clara cells appeared deformed and collapsed. This cell population was markedly reduced by seven days after TCE exposure, and the bulging apices characteristic of this cell type were virtually absent, resulting in a flattened epithelial lining. By 15 and 30 days after TCE, reparative processes were evident and micronodules consisting of multiple Clara cells protruded into the airway lumen. The administration of TCE to mice causes severe morphological damage to Clara cells of the bronchiolar epithelium which persists for at least 60 days after chemical exposure.     

Comparison of 3D computer-aided with manual cerebral aneurysm measurements in different imaging modalities

Introduction

To compare intra- and inter-observer reliability of aneurysm measurements obtained by a 3D computer-aided technique with standard manual aneurysm measurements in different imaging modalities.

Methods

A total of 21 patients with 29 cerebral aneurysms were studied. All patients underwent digital subtraction angiography (DSA), contrast-enhanced (CE-MRA) and time-of-flight magnetic resonance angiography (TOF-MRA). Aneurysm neck and depth diameters were manually measured by two observers in each modality. Additionally, semi-automatic computer-aided diameter measurements were performed using 3D vessel surface models derived from CE- (CE-com) and TOF-MRA (TOF-com) datasets. Bland–Altman analysis (BA) and intra-class correlation coefficient (ICC) were used to evaluate intra- and inter-observer agreement.

Results

BA revealed the narrowest relative limits of intra- and inter-observer agreement for aneurysm neck and depth diameters obtained by TOF-com (ranging between ±5.3 % and ±28.3 %) and CE-com (ranging between ±23.3 % and ±38.1 %). Direct measurements in DSA, TOF-MRA and CE-MRA showed considerably wider limits of agreement. The highest ICCs were observed for TOF-com and CE-com (ICC values, 0.92 or higher for intra- as well as inter-observer reliability).

Conclusion

Computer-aided aneurysm measurement in 3D offers improved intra- and inter-observer reliability and a reproducible parameter extraction, which may be used in clinical routine and as objective surrogate end-points in clinical trials.     

Morphologic changes and covalent binding of 1,1-dichloroethylene in Clara and alveolar type II cells isolated from lungs of mice following in vivo administration

We have investigated the metabolism and covalent binding of 1,1-dichloroethylene (1,1-DCE) in isolated unseparated lung cells and in enriched fractions of Clara and alveolar type II cells from mice. Lung cells from control mice separated by centrifugal elutriation were viable and metabolically active as assessed by measurements of 7-ethoxycoumarin deethylase, NADPH cytochrome c reductase, and glutathione S-transferase activities, which were highest in fractions enriched in Clara cells. Mice were treated with [14C]1,1-DCE (125 mg/kg; 20 microCi/kg) in vivo and, 1 hr later, lung cells were isolated and binding of [14C]1,1-DCE determined. Covalent binding was highest in the Clara cell fraction (480 +/- 205 pmol/10(6) cells; 41% Clara cell purity) when compared to the levels present in the fractions containing type II cells (126 +/- 63 pmol/10(6) cells; 51% type II cell purity) and mixed cells from whole lung (29 +/- 13 pmol/10(6) cells). Ultrastructurally, alveolar type II cells from lungs of control and 1,1-DCE-treated mice exhibited normal morphology with well-preserved lamellar bodies. Whereas Clara cells isolated from lungs of control mice appeared structurally unimpaired, those from the lungs of 1,1-DCE-treated mice displayed severe damage and disruption of cellular organelles. The results of these experiments demonstrate the highest binding of [14C]1,1-DCE-metabolite(s) in Clara cells, whereas significantly lower binding was found in both alveolar type II and unseparated lung cells. The substantial binding of [14C]1,1-DCE in Clara cells correlated positively with the high monooxygenase capacity and the preferential damage sustained by this cell population.     

Distribution of cytochrome CYP2E1 in murine liver after ethanol and acetone administration.

The effects of acetone and ethanol administration on cytochrome CYP2E1 in murine liver were investigated. A monoclonal antibody (Mab 1-98-1) specific to rat ethanol-inducible P450 recognized a major band of Mr 51,000 in Western immunoblots of mouse liver microsomes. This band was increased 1.8-fold by 10% ethanol in drinking water for 2 weeks, 4.7-fold by 1% acetone in drinking water for 1 week, and 2.5-, 2.1- and 6.8-fold by ethanol in a liquid diet for 9 days, 2 weeks and 3 weeks respectively. Immunohistochemical staining experiments with the same antibody showed specific localization in centrilobular regions of liver lobules, with variations in intensity that corresponded to differences detected in Western immunoblots. Uniform cellular increases in centrilobular staining occurred with all ethanol treatments, whereas a more heterogeneous increase in individual cells was noted after acetone. Lipid accumulation in hepatocytes was pronounced after 3 weeks on the ethanol liquid diet but was less so in other treatment groups, and thus did not consistently correlate with enzyme induction. Microsomal aniline p-hydroxylase activity was also induced by the acetone and ethanol treatments, with a progressive increase from 9 days to 3 weeks on the ethanol liquid diet. Changes in this activity in general paralleled those found with immunohistochemistry and immunoblotting. The results demonstrate that (i) the mouse is a good model for correlative biochemical and histochemical studies of CYP2E1 induction, (ii) in the mouse liver, this P450 is preferentially localized in centrilobular regions constitutively as well as in induced states, (iii) the centrilobular pattern varies under different induction conditions, and (iv) there is a progressive inductive increase in CYP2E1 protein and enzyme activity with chronic ethanol treatment over at least 3 weeks.     

The relationship between lung volume and standard scalar ECG parameters in normal subjects

Although the relationship between abnormalities in the ECG and lung volumes has been well described in patients with chronic obstructive lung disease, little is known about this relationship in normal subjects. We investigated this relationship in normal, supine subjects at lung volumes ranging from residual lung volume to total lung capacity. We found that there was a significant right shift in the frontal axis with increasing lung volume. Over the precordium, R wave amplitude decreased mainly at the lateral leads and S wave amplitude increased chiefly at the anterior leads. These results are consistent with a normal vertical shift and clockwise rotation of the heart with increasing lung volume.     

Computer-aided nidus segmentation and angiographic characterization of arteriovenous malformations

Purpose

Exact knowledge about the nidus of an arteriovenous malformation (AVM) and the connected vessels is often required for image-based research projects and optimal therapy planning. The aim of this work is to present and evaluate a computer-aided nidus segmentation technique and subsequent angiographic characterization of the connected vessels that can be visualized in 3D.

Methods

The proposed method was developed and evaluated based on 15 datasets of patients with an AVM. Each dataset consists of a high-resolution 3D and a 4D magnetic resonance angiography (MRA) image sequence. After automatic cerebrovascular segmentation from the 3D MRA dataset, a voxel-wise support vector machine classification based on four extracted features is performed to generate a new parameter map. The nidus is represented by positive values in this parameter map and can be extracted using volume growing. Finally, the nidus segmentation is dilated and used for an automatic identification of feeding arteries and draining veins by integrating hemodynamic information from the 4D MRA datasets.

Results

A quantitative comparison of the computer-aided AVM nidus segmentation results to manual gold-standard segmentations by two observers revealed a mean Dice coefficient of 0.835, which is comparable to the inter-observer agreement for which a mean Dice coefficient of 0.830 was determined. The angiographic characterization was visually rated feasible for all patients.

Conclusion

The presented computer-aided method enables a reproducible and fast extraction of the AVM nidus as well as an automatic angiographic characterization of the connected vessels, which can be used to support image-based research projects and therapy planning of AVMs.