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Biomedical subjects

W M Thurlbeck

Publications and source records attributed to W M Thurlbeck.

At least 19 recordsLinked to original sources
PubMed1992

The in vitro effect of triamcinolone acetonide on branching morphogenesis in the fetal rat lung.

We have studied the effect of triamcinolone acetonide (TAC) on airway morphogenesis of the Sprague-Dawley fetal rat in whole organ lung cultures from day 15 to day 21 of equivalent gestational age (6 days in culture). TAC produced an increased number of peripheral buds from day 18 onward and the airway and airspaces had larger lumens. Airway branching was increased compared to controls, and there was a higher proportion of airway epithelium and a lower proportion of mesenchyme. Cell height was significantly lower in TAC treated lungs except on day 17. This was due to accumulation of glycogen prior to the increased branching activity. In both controls and TAC-treated lungs, peripheral bud number and volume proportion of epithelium increased with time in culture, whereas volume proportion of mesenchyme, mean chord length of airways and airspaces, and epithelial cell height decreased. These changes were more pronounced in the TAC-treated group and were significant. However, TAC-treated lungs were morphologically irregular. We conclude that TAC has a direct effect on airway morphogenesis and it promotes growth of morphologically abnormal lungs. TAC also appears to enhance airway branching and morphologic changes interpreted as increased epithelial maturation.

Animals↗
PubMed1992

Analysis of the structure of the muscular pulmonary arteries in patients with pulmonary hypertension and COPD: National Institutes of Health nocturnal oxygen therapy trial.

We examined the cardiovascular function as well as the structure of the muscular pulmonary arteries in patients who had died while enrolled in the National Institutes of Health nocturnal oxygen therapy trial (NOTT). The cardiovascular function of the patients classified into groups based on the severity of the pulmonary hypertension was examined, and we compared the morphologic data in these groups to those obtained from age-matched controls who died with no evidence of cardiovascular disease. The groups with severe pulmonary hypertension had markedly increased pulmonary vascular resistance but similar cardiac index to the group with only mild hypertension. In the structural analyses, we found definite alterations in arterial structure from the control population: the patients who had pulmonary hypertension had markedly increased percentages of intima and media. These differences were most pronounced in the medium and larger muscular arteries. The degree of pulmonary hypertension did not appear to alter vascular structure consistently, although there was a trend towards an increase in muscle media in the smaller vessels. When the patients were classified into a group who responded to oxygen administration by a decrease in Ppa, and an age- and Ppa-matched group who did not respond, there were no differences in vascular structure between these groups, although both groups had greater percentages of intima and media compared to the control group. We conclude that, in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD), there are structural alterations of the muscular pulmonary arteries, but these do not correlate with either the severity of the pulmonary hypertension or the ability of the pulmonary vasculature to respond to oxygen administration.

Adult↗
PubMed1992

Lung growth in newborn guinea pigs: effects of endurance exercise.

Newborn Hartley albino guinea pigs were exercised daily on a rodent treadmill at 25 m/min, 0 degree grade for a maximum of 1 1/2 h. Groups were exercised for 1, 2 and 3 weeks. Controls were age-matched sedentary animals. A separate group of animals was sacrificed after 12 h of life to establish baseline lung growth data. A morphological and biochemical comparison was made between the lungs of exercised and sedentary animals. No effect of exercise on lung growth was observed. After 2 weeks of exercise animals had diminished somatic growth compared to the controls. The data was pooled from exercised and control guinea pigs at 1 and 3 weeks, at which time there were no differences, in order to obtain normal growth data. The only change between 0 week and 1 week was a slight increase in femur length. Between 1 week (and also 0 week) and 3 weeks there were significant increases in lung volume, lung weight, protein content, inter-alveolar wall distance, mean chord length of alveoli and ducts, and gas exchanging surface area. The guinea pig lung is well alveolated at birth and there was no evidence of subsequent alveolar multiplication. Enlargement of airspaces suggested that lung growth was primarily brought about by dilation. The lack of alveolar multiplication following exercise may be due to the fact the alveoli are fully developed at birth.

Age Factors↗
PubMed1992

A comparative study of postpneumonectomy compensatory lung response in growing male and female rats.

Postpneumonectomy compensatory lung response and normal lung growth in the early postnatal period were studied in male and female rats. Four-week-old litter-matched male and female Sprague-Dawley rats were subjected to left pneumonectomy or sham operation and followed for 3 wk. In both sexes after pneumonectomy, lung weight (WL), lung volume (VL), alveolar surface area (Sw), total alveolar number (N(at)), and the amount of DNA and protein increased significantly. In both males and females, WL, VL, and Sw matched those of both lungs of the sham-operated group, but N(at) and the amount of DNA and protein did not. Female pneumonectomy and sham-operated rats were smaller in body weight than males. Absolute WL, VL, Sw, N(at), and the amount of DNA and protein were significantly lower, but specific parameters (per unit body weight) were significantly greater in females than in males. After pneumonectomy, the postcaval lobe increased most in volume (70 and 73% in males and females, respectively). Mean linear intercept and mean chord length of alveoli increased, and the number of alveoli per unit volume decreased more in the postcaval and middle lobes than in upper and lower lobes in both sexes. Postpneumonectomy, loss of elastic lung recoil was observed in females. We conclude that, in certain aspects (WL, VL), compensatory growth matched both lungs of controls, but in others (biochemical, morphometric) it did not. There was evidence of alveolar multiplication, but the dominant effect was enlargement of air spaces.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1992

Idiopathic pulmonary fibrosis. Quantitative assessment of lung pathology. Comparison of a semiquantitative and a morphometric histopathologic scoring system.

The objective of this study was to determine the accuracy of a semiquantitative method of assessing the relative degree of cellularity and fibrosis compared with a morphometric analysis of specific histopathologic features in idiopathic pulmonary fibrosis (IPF). Morphometric analysis was performed on biopsy tissue from 20 patients. Morphometry showed that approximately 70% of parenchymal tissue was abnormal: 35% cellular consolidation and fibrosis, 20% honeycomb changes, 10% thick alveolar septa, and 5% small airways within abnormal parenchymal tissue. The prominent components of the abnormal parenchymal tissue were extracellular fibers, an abundance of interstitial cells, and epithelial cell hyperplasia. Correlation between four groupings of pathologic features, identified by a semiquantitative analysis, and each of the components of the parenchymal lesions showed significant correlations between (1) the fibrotic or reparative factor (alveolar wall metaplasia, fibrosis, honeycombing, and smooth muscle and vascular changes) and components of honeycomb lesions (extracellular fibers, interstitial cells, and epithelial injury and repair), and (2) the inflammatory and exudative factor and extracellular fibers in the lesions. These results support that the scoring system used by the pathology panel provides an accurate assessment of pathologic features useful in the assessment of the extent and severity of the histopathologic lesions of IPF.

Biopsy↗
PubMed1992

DNA synthesis and related enzymes altered in compensatory lung growth in rats.

Left pneumonectomy was performed on 4 week-old male Fischer-344 rats. Changes in DNA biosynthesis and the activities of related enzymes were studied in the contralateral lungs of the pneumonectomized animals (n = 55) and compared with sham-operated (n = 55) and untreated control animals (n = 40) The wet weight of the contralateral lung of the pneumonectomized rats reached that of both lungs of the untreated and sham-operated rats 14 days after the operation. The activities of thymidine kinase and DNA polymerase from the regenerating lungs were elevated on Days 1 and 7. To determine the molecular forms of DNA polymerase in the crude extract, phosphocellulose column chromatography was performed. The type of DNA polymerase with the highest activity was alpha in regenerating lung on Days 1, 3, and 7. These results suggest that DNA replication for cellular proliferation was elevated in the remaining lung after pneumonectomy. In addition, an interlobar difference in DNA biosynthesis was observed in the remaining lung. The increase was especially marked in the cardiac lobe, followed by increases in the DNA content of the remaining lobes on Day 7. From these observations we conclude (1) that increased activity of DNA polymerase alpha is likely to be an initial change in compensatory lung growth, and may be caused by some unknown stimulator in lung tissue, and (2) that DNA biosynthesis may differ among the lobes of the lung, at least until 3 days post-pneumonectomy.

Animals↗
PubMed1992

Prematurity and the developing lung.

Bronchopulmonary dysplasia results from treatment of immature lungs resulting from an abnormally short gestation or from pulmonary hypoplasia. Lung hypoplasia secondary to lung compression, oligohydramnios, or diminished complexity of tissue. Normal lung development and the pathologic process associated with lung hypoplasia and their effects of postnatal lung structure are reviewed.

Anencephaly↗
PubMed1991

Morphometric and biochemical changes in lungs of growing rats treated with a calmodulin antagonist.

To determine the role of calmodulin in postnatal lung growth and development, 4-week-old rats were injected intraperitoneally on consecutive days with trifluoperazine (TFP), a potent and specific calmodulin antagonist, for a period fo 3 weeks and studied in comparison with normal controls and undernourished weight-matched animals. TFP treatment resulted in stunting of lung growth such that observed normal increments in morphometrically determined total number of alveoli and alveolar surface area and in biochemically determined DNA, elastin, and collagen contents of the lungs were diminished in comparison with age-matched normal controls. However, the TFP treatment also resulted in reduced daily food intake and body weight gain. In the TFP group, lung weight and lung volume were also reduced compared with the weight-matched control group. This resulted in reduced alveolar surface area, total number of alveoli, DNA, collagen, and elastin in the TFP group compared with values in the weight-matched controls. Thus the TFP-induced lung changes were not due to inanition and/or reduced somatic growth. The TFP treatment resulted in reduced activities of calmodulin and cyclic adenosine monophosphate (cAMP)-phosphodiesterase in the lungs of the animals, independent of their nutritional status. Based on these findings, we suggest that calmodulin may be an important regulatory component of postnatal lung growth and development.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1991

Alveolar attachments in emphysema of human lungs.

We have studied alveolar attachments to membranous bronchioles in 41 patients enrolled in the National Institutes of Health Intermittent Positive Pressure Breathing Trial who died, came to autopsy, and provided adequate tissue for examination. The patients had moderate to severe chronic airflow obstruction and, on the average, severe emphysema. We measured the number of normal attachments per membranous bronchiole per case (N), the number of normal attachments per mm of circumference per bronchiole per case (Nunit), and the ratio of abnormal to all attachments (R). All measurements correlated closely to all measurements of emphysema and to irregular shape of bronchioles (deformity index). Measurement of abnormal attachments correlated with abnormal tests of pulmonary function, including evidence of airflow obstruction and diffusing capacity for carbon monoxide (DLCO). Nunit showed the most frequent correlations, but both N and Nunit were only related independently of emphysema for Phase III of the single-breath nitrogen test. R was related to loss of DLCO. We conclude that loss of attachments is not itself a cause of airflow obstruction but rather a correlate of emphysema, which is the proximate cause of the obstruction. Loss of alveolar attachments has an effect only on the single-breath nitrogen tests independent of emphysema.

Bronchi↗
PubMed1991

Quantitative assessment of lung pathology in idiopathic pulmonary fibrosis. The BAL Cooperative Group Steering Committee.

The diagnosis and classification of most interstitial lung diseases requires histologic evaluation of lung tissue, obtained by an open lung biopsy to confirm the diagnosis. In addition, it is generally accepted that response to therapy in idiopathic pulmonary fibrosis (IPF) is related to the relative degree of cellularity and fibrosis present. Because only a qualitative assessment of the relative extent and severity of these changes is generally provided, correlation with clinical and physiologic alterations is difficult. This report describes results of a semiquantitative assessment by four pathologists of inflammatory/exudative changes, fibrotic/reparative changes, and airway alterations, in addition to an overall assessment of cellularity and fibrosis in 50 patients with IPF. In 10 randomly selected biopsies examined twice in a blinded fashion, absolute agreement between assessments for a given pathologist varied between 54 and 64% (mean = 57.5%) and in the majority of instances the agreement was greater than would have occurred by chance. There was good agreement for most variables across the four raters on the 101 samples. The mean score for some of the parameters reported by a given rater deviated occasionally from those of the other raters, but no single rater was consistently different from the other raters. A principal component factor analysis revealed that the pathologic features fell into four general groupings: alveolar wall metaplasia, fibrosis, honeycombing, smooth muscle, and vascular changes fell into one group; severity and extent of cellularity in the alveolar wall into a second group; severity and extent of cellularity in the alveolar space into a third group; and interstitial young connective tissue along with granulation tissue in the airways formed the fourth group.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1991

Scanning electron microscopic observations of emphysema in humans. A descriptive study.

We have performed dissecting light and scanning electron microscopy (SEM) on 14 lungs with mild centrilobular emphysema, two of which also had mild panacinar emphysema. The lungs were surgically resected, mainly for cancer. The walls of centrilobular emphysema were either thick or thin. The former were less common and represented fibrosis of the walls. The latter were less fibrotic, but some fibrosis was seen. Adjacent alveoli were compressed and distorted, and overlapping walls of air spaces occurred. In panacinar emphysema alveolar ducts were enlarged and flattened with transverse linear bands interpreted as flattened walls of enlarged alveoli. The walls of air spaces were chiefly lined by type I and type II epithelial cells, but occasionally bronchiolar epithelium lined the proximal emphysematous spaces. Supplying bronchioles showed diminished numbers of ciliated cells with cilia of reduced height. SEM was much more sensitive than dissecting microscopy in recognizing emphysema. The apparent fibrosis suggests that the definition of emphysema may have to be reconsidered and that if fibrosis is apparent, the proteolysis-antiproteolysis hypothesis of the pathogenesis of emphysema may have to be modified.

Carcinoid Tumor↗
PubMed1990

Pathophysiology of chronic obstructive pulmonary disease.

Chronic airflow obstruction (CAO) is a syndrome that is produced by a variety of lesions which may occur in bronchi (large airways), bronchioles (small airways), and lung parenchyma (gas exchanging lung). These lesions frequently occur together in various combinations because of a common etiologic agent, tobacco smoke. Occasionally, one lesion or another may play a dominant role. The major disease of the large airways is chronic bronchitis, or chronic sputum production, and it is defined clinically. Its morphologic counterpart is mucous gland enlargement. Mucous gland enlargement is poorly related to CAO. Other lesions of the large airways--inflammation, smooth muscle hyperplasia, cartilage atrophy, and bronchial wall thickening--have also been described, but their functional consequences are uncertain. Bronchiolar lesions are well recognized in CAO, but their relative importance may differ in patients with mild CAO, compared to patients with severe CAO. In mild CAO, inflammation is a very important lesion, and its probable consequences--narrowing, fibrosis, and goblet cell metaplasia--have all been found to be important. In severe CAO, inflammation and fibrosis do not appear to be important, but goblet cell metaplasia, bronchiolar tortuosity, and narrowing do. Emphysema is a subset of airspace enlargement. Emphysema is defined anatomically and is the most important component of severe CAO. Several forms of emphysema can be recognized morphologically and may have specific clinical associations. However, in the usual patient with severe CAO, it is the severity, rather than the type, of emphysema, that is most significant. The diagnosis of emphysema depends on a combined approach. Significant factors include the clinical history (age, sex, smoking, chronic bronchitis, dyspnea), radiologic evidence of overinflation, and diminished diffusing capacity for carbon monoxide.

Bronchi↗
PubMed1979

Morphologic aspects of bronchopulmonary dysplasia.

Some of the morphologic changes of bronchopulmonary dysplasia are frequently found in infants dying of the infantile respiratory distress syndrome, so the frequency of BPD is more frequent as determined morphologically than as determined clinically. Morphologic differences have been described between the lesions of oxygen poisoning and those of BPD, but there are probably no true qualitative differences and such differences as exist are quantitative ones. Clinical and functional studies suggest that lung damage in infancy and early childhood may result in residual functional abnormalities in older childhood, and to a predisposition to chronic airflow obstruction in later life. It is hypothesized that this may be brought about by alteration in postnatal lung growth. Two patients who had an operation for diaphragmatic hernia on the first day of life and who died 8 and 64 months later were used to illustrate this point, since both had obviously abnormal lung structure at the time of death.

Adult↗
PubMed1979

Postnatal lung growth after repair of diaphragmatic hernia.

The lungs of two patients who died eight months and 64 months after repair of a left-sided diaphragmatic hernia on the first day of life were examined. Lung volumes were appropriate for the size of the children, and the ratio of right lung volume to left lung volume was also normal in both patients. The lungs, however, were grossly abnormal with evidence of enlargement and destruction of respiratory tissue. The left lung was affected more than the right in both subjects. In one patient the total number of alveoli in the lungs was similar to that of normal children of the same age, but this was because the right lung had more than twice as many alveoli as the left lung. It appears that alveolar multiplication is impaired after repair of diaphragmatic hernia. The number of bronchioles was reduced in the infant with very few alveoli, and there may have been too few bronchioles in the other patient.

Child, Preschool↗