Treatment of mucus hypersecretion in human disease.
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Biomedical subjects
Publications and source records attributed to L Reid.
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The application of quantitative morphometric techniques to evaluation of the lungs of nine children who died with a ventricular septal defect between the ages of 3 months and 4 years showed that the presence of pulmonary hypertension interferes with the growth and development of the pulmonary circulation. In all cases the preacinar arteries were of normal size and not dilated, and arterial size and number within the acinus were reduced and similar to those seen in the normal child at birth. Arterial and venous muscularity was increased as judged by an increase in wall thickness and by the presence of muscle in smaller and more peripheral arteries than is normal. Elevation of resistance was associated with failure of the intraacinar pulmonary circulation to develop normally rather than to obliterative pulmonary vascular disease. In view of the rapidity with which impairment of growth and elevation of resistance can develop, closure of a large defect is recommended before age 2 years.
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Quantitative morphometric techniques have been applied to the injected and inflated lung and to the heart in 9 infants with total anomalous pulmonary venous return dying with obstruction to pulmonary venous return. In 5 (mean age at death 55 days) pge 20 days) to an infradiaphragmatic site. Structural changes were present in the pulmonary circulation in all patients, even in the youngest, an 8-day-old child. In both types of total anomalous pulmonary venous return increased arterial muscularity was severe, as shown by increase in wall thickness and by extension of muscle into smaller and more peripheral arteries than normal; these changes tended to increase with age. Where the pulmonary venous blood drained to a supradiaphragmatic site, the severity of arterial medial hypertrophy correlated inversely with the magnitude of the pulmonary: systemic flow ratio, increasing as the pulmonary blood flow fell. Vein wall thickness was increased and in all but the youngest child the veins were 'arterialised'. At the lung periphery the arteries and alveoli appeared to have multiplied normally. Arterial size varied according to whether pulmonary venous blood drained above or below the diaphragm; the diameter of pre- and intra-acinar arteries was increased only in cases where the pulmonary venous return drained to a supradiaphragmatic site, being normal when it drained to an infradiaphragmatic site. In the heart the left ventricle was of normal size in all but one case. Dilation and severe hypertrophy of the right ventricle and septum were present only in cases of drainage to a supradiaphragmatic site. In the older patients with the latter anomaly dilation of the pulmonary arteries and right ventricle suggested that a large left-to-right shunt had preceded the onset of obstruction to pulmonary venous return and that the more severe right ventricular and septal hypertrophy in these cases might be the result of a longer duration of pulmonary hypertension. In contrast, in total anomalous pulmonary venous return to an infradiaphragmatic site it appears that obstruction to pulmonary venous return develops soon after birth and prevents a large increase in pulmonary blood flow, and thus neither the pulmonary arteries nor the right ventricle become dilated. In infants with total anomalous pulmonary venous return and obstruction to pulmonary venous return, it is striking how rapidly the pulmonary circulation develops new muscle.
Study of the structural features of the pulmonary circulation in various types of congenital heart disease makes it possible to correlate function and structure in the fetal and newborn lung. We applied quantitative morphometric techniques to the injected and inflated lungs of newborn infants who had died with obstruction to left ventricular outflow from aortic atresia, stenosis, or coarctation. The structure and development of the pulmonary circulation was judged by the number of arteries and veins and their size and wall structure, with particular attention to vessels within the respiratory unit. The study established for the first time that the structure of the pulmonary circulation is modified by the antenatal abnormalities in blood flow that occur through the heart and great vessels in the presence of congenital heart disease. Fetal multiplication of intra-acinar arteries in aortic atresia and stenosis is increased as also is the muscularity of both pre- and intra-acinar arteries and veins, muscle extending into smaller and more peripheral vessels than is normal at birth. When the pulmonary circulation is normal before birth but arterial pressure and flow are abnormally increased at birth, as in coarctation with patent ductus and ventricular septal defect, an increase in arterial diameter and muscularity is apparent within the first week of life.
The lungs of eight newborn infants who had died from pulmonary atresia were studied by quantitative morphometric techniques. It was established for the first time that the abnormal pattern of blood flow through the heart and great vessels in a fetus with pulmonary atresia is associated with impaired lung development as shown by arteries that are too few, too small, and with an abnormally thin muscle coat, although the distribution of muscle along the arterial pathway is normal. Differences between the cases in the degree of impairment of lung development could be detected and related to the degree of reduction in pressure and flow before birth in the individual case. Although blood flow through the pulmonary circulation is small before birth lung development seems sensitive to any further reduction.
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Sputum produced by normal subjects after inhalation of prostaglandin F2alpha, acetylcholine, histamine, and citric acid has been analysed. Prostaglandin F2alpha was the most effective of the drugs in promoting sputum production. The material expectorated after inhalation of prostaglandin F2alpha shows the characteristics of mucoid sputum from patients with chronic bronchitis. The apparent viscosity and the concentration of marker substances for bronchial glycoprotein was in the lower part of the range found in mucoid chronic bronchitic sputum. The concentration of marker substances for serum glycoproteins and tissue fluid transudate were below the range found in chronic bronchitis, indicating that, in disease states, in addition to bronchial mucus there is a marked tissue fluid transudate component. Sputum produced after inhalation of acetylcholine and histamine contained relatively more tissue fluid transudate than sputum produced after inhalation of prostaglandin F2alpha, Sputum produced after inhalation of prostaglandin F2alpha, is of special value in indicating the nature of secretion from normal airways.
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Pulmonary hypertension has been induced in rats by 2 weeks' exposure to hypoxia, equivalent to an altitude of approximately 5500 m, in a hypobaric chamber. The rats were removed from the chamber and allowed to recover for up to 8 weeks at atmospheric pressure. Precise quantitative microscopic techniques after injection of the pulmonary artery have been used to estimate the regression in the pulmonary artery of the structural changes associated with pulmonary hypertension. During recovery the degree of muscularization of the pulmonary arteries decreases by disappearance of muscle cells from the small arteries and a drop in arterial wall thickness of larger vessels. These changes do not seem to reflect pulmonary artery pressure directly, since right ventricular hypertrophy regresses at a faster rate. In hypertensive rats there is a "loss" of small arteries in the alveolar region and little filling of precapillary vessels. On recovery, some of the vessels fill, suggesting that encroachment on the lumen by muscle and endothelial cells has lessened. Even after 8 weeks' recovery, however, some arteries do not return, suggesting they have completely disappeared and that regions are left with relatively little perfusion. This reduction of vascular reserve presents without there being right ventricular hypertrophy.
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A quantitative analysis has been made of the glycoproteins present in the goblet cells of the epidermis, gill filaments and gill lamellae of three species of teleost fish. The glycoproteins have been identified by a combination of techniques, including the use of the enzyme sialidase followed by Alcian Blue staining, at PH 2.6 or 1.0, in combination with periodic acid-Schiff. The selected fish were representative of species living in marine, freshwater and estuarine environments. The range of glycoproteins identified in these fish was similar to that found in mammalian tissue in that both neutral and acid glycoproteins were present, the latter included both sialomucins sensitive and resistant to sialidase, and sulphomucin. A single goblet cell contained either neutral or acid glycoproteins alone or in combination. Only the epidermis of the plaice and rainbow trout contained uniform cell populations producing acid glycoproteins, the former sulphomucin and the latter mainly sialomucin. At each site in the flounder and in the gill epithelia of the plaice and rainbow trout, the goblet cell population was mixed, with cells producing each type of glycoprotein. The number of goblet cells producing each type of glycoprotein varied at each tissue site.
Three infants died with pulmonary hypertension of unknown cause during the first three months of life. Their lungs were examined using quantitative morphologic techniques. In all three cases the intra-acinar pulmonary arteries were more muscular than normal, as shown both by an increase in thickness of the muscle coat in arteries which are normally muscular, and by extension of muscle into smaller and more peripheral intra-acinar arteries not normally muscular at this age. It is suggested that "persistent pulmonary hypertension" of the newborn infant is, in some infants, due to a structural abnormality of the pulmonary circulation which is present at birth.
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Quantitative analysis has been used to assess growth in a lung from an infant aged 21/2 months in whom a diaphragmatic hernia was repaired at birth. The lungs had been abnormally small at birth but at 21/2 months were of normal volume. Alveoli had multiplied at the normal rate after birth but had not reached the number normal of age. The number per acinus was normal but the alveoli were increased in size, particularly in the left lung. The airway number, and thus alveolar, acinar, and arterial number, were all reduced in both lungs, the ipsilateral being most affected. The pulmonary blood vessels in both lungs showed an increased muscularity that did not correlate with lung volume or alveolar number, a feature that may have been present at birth. The degrees of hypoplasia in the two lungs were different at birth and this difference had been maintained. The effect of the disturbance to lung growth on the functioning of the lung is discussed.
Cell turnover in the rat airway epithelium has been studied at 5 levels of the bronchial tree after administration of either colchicine or tritiated thymidine, and in male and female rats of 3 age groups. This is the first study to include all these features of the same species. In the young animals the Mitotic Index (number of cells in division per 1,000 nuclei) decreased progressively to the periphry and was higher in the male than in the female, although the rate of weight gain was the same for both. In the oldest animals no difference was observed between the various airway levels or between the sexes. In the intermediate group the proximal to distal decrease was apparent but the difference with sex was not. The concentration of cells per unit length of airway is higher in the trachea and main bronchus than in intrapulmonary airways. (In the intrapulmonary airways virtually no basal cells are present.) This means that a given Mitotic Index represents replacement of a larger area of epithelium in small airways than in large ones.