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On defining microcardia: application in pulmonary emphysema.

Pulmonary emphysema was the disease entity from which we derived a definition for microcardia in males. After the fourth decade, a cardiothoracic ratio of 38% or less is considered to represent a small heart. Among male Veterans Hospital patients between the ages of 41 and 83, the probability of an individual without emphysema having a cardiothoracic ratio of 38% or less was under 1%. Microcardia, even as an isolated sign, should make one suspect strongly the presence of subclinical emphysema and to consider instituting a prophylactic regimen. Hearts should be measured to judge not only increased size but decreased size in both patient and examinee groups.

Adult

[Pulmonary emphysema. Changes in the pulmonary function of experimentally induced emphysema].

By intratracheal injection of the protease papain to experimental animals parenchymal changes in the lung can be induced, that resemble human emphysema. Papain (dosage 26 to 112 mg, 1 to 4 injections) was given intratracheally to 8 bastard dogs (weighing from 12.5 to 20 kg) during light general anesthesia. Pulmonary function was assessed in weekly intervals and related to morphologic changes in the lung. Static compliance of the lung and FRC measured during respiratory arrest were increased after papain, bronchial resistance, measured while artifically ventilated at constant pressure was also increased. Changes of static lung compliance and FRC were seen after the first administration of papain, but further increased with time of observation and after multiple doses of papain. Increase of resistance was not found before 5 weeks. At quiet breathing resistance was not increased at all. No significant changes were found of arterial pO2 and pCO2, pH, standard and actual bicarbonate, diffusion capacity for O2, tidal volume, minute ventilation and ventilatory rate. Morphological findings confirmed the changes described by others. Pulmonary function appears to be pathological at a time when morphology still seems to be normal. The question is discussed to what extent the model of experimental emphysema induced by proteolytic enzymes can contribute to the understanding of human pulmonary emphysema. Lung function in the course of experimental emphysema is compared with function in different clinical types of emphysema.

Acid-Base Equilibrium

[Bronchospirometric results after single lung homotransplantation in dogs with experimentally induced pulmonary emphysema (author's transl)].

Pulmonary emphysema was induced in 8 bastard dogs by intratracheal instillation of Papain. Development of emphysema was documented by pulmonary function tests. The emphysematous animals underwent single lung homotransplantation. Postoperative bronchospirometric measurements revealed that up to the 6th week after transplantation there is no evidence of serious ventilation perfusion inbalance.

Airway Resistance

[Synoptical X-ray diagnostics of pulmonary emphysema (author's transl)].

In marked chronic obstructive pulmonary emphysema, especially in the classical emphysematous type of abnormal thorax, a good correlation can be found between the anteroposterior expansion of the thorax, the reduced inspiratory capacity, the clinical state, disturbed mechanics of breathing and the x-ray-state. On the contrary, in clinical emphysema of a lower degree, especially in subclinical, i. e. in predominantly asymptomatic pulmonary emphysema of the elderly, the effectiveness of the roentgenological examination is very small.

Aged

Subcutaneous and pulmonary emphysema as complications of bovine ephemeral fever.

Subcutaneous and pulmonary emphysema was observed in some cattle on farms on which outbreaks of bovine ephemeral fever (BEF) occurred. BEF virus was isolated in baby hamsters from one of the cases and cattle were injected with blood from this animal. Although the experimental animals developed typical BEF symptoms, no signs of emphysema could be detected by clinical and pathological examinations. The histopathological changes in the skeletal muscle and synovial membranes of the natural case resembled those of BEF described by Basson, Pienaar & Van der Westhuizen (1970). The lumina of the terminal and respiratory bronchioles in the lungs were obliterated by cellular debris and the muscular portion of some of these bronchioles was necrotic. The possible pathogenesis of pulmonary emphysema is discussed.

Animals

Evaluation of cardiac size in chronic bronchitis and pulmonary emphysema.

The accuracy of interobserver variability of roentgenographic analysis for cardiac size in patients dying with chronic bronchitis and pulmonary emphysema were correlated with pathologic data derived from special studies. Three trained observers were able to accurately and consistently diagnose chronic bronchitis and pulmonary emphysema and to detect cardiomegaly on the chest x-ray film. The best criteria for chronic bronchitis and pulmonary emphysema were those of overinflation; however, none of the roentgenographic criteria usually suggested for the specific diagnosis of right ventricular or left ventricular hypertrophy were found to be reliable. The inaccuracy and interobserver variability in the detection of enlargement of specific chambers make it evident that the usual criteria are not valid and that roentgenographic appraisal of cardiac size in these patients in limited to findings of normalcy or cardiomegaly.

Autopsy

Toxicity of aerosol propellants in the respiratory and circulatory systems. VII. Influence of pulmonary emphysema and anesthesia in the rat.

Experimental induction of pulmonary emphysema caused an increase in sensitivity of the rat to toxicity from inhalation of propellants. The emphysematous rat showed an exaggerated reduction in pulmonary compliance in response to inhalation of trichlorofluoromethane (FC 11). In emphysematous and non emphysematous rats without anesthesia the inhalation of FC 11 caused tachycardia, arrhythmias and other abnormalities in the electrocardiogram. The tachycardiac response was eliminated by induction of barbiturate anesthesia, which increased the sensitivity of the heart to occurrence of abnormalities in the electrocardiogram in response to inhalation of FC 11 as well as of dichlorodifluoromethane (FC 12) and difluoroethane (FC 152a). The acceleration in heart rate in response to inhalation of FC 11, hypoxia or hypercapnea was prevented by prior treatment with a beta-blocking drug.

Adrenergic beta-Antagonists

The pathogenesis of pulmonary emphysema (II).

The most important primary cause of generalized pulmonary emphysema is in all probability the loss of mechanical stability of the connective tissue framework in the lung parenchyma. The complexity of the interrelations and interdependencies between the fibres and the ground substance, leads to the mapping out of a more detailed outline of the vulnerable parts in a similar framework. It is concluded that the junctions especially constitute weak spots. Glycosaminoglycans, glycoproteins and proteoglycans particularly hold a key position as cementing substances. The importance of female sex hormones in the metabolism of the ground substance is indicated. A survey is given of the possible threats to a similar system. An attempt is made to disentangle the multitude of possible pathogenetic pathways which lead to emphysematous disintegration. Perspectives of future emphysema research are discussed on the basis of these considerations. Preventive, protective, and reconstructive measures are proposed.

Ascorbic Acid

Experimental pulmonary emphysema in Syrian hamsters.

Syrian hamsters were exposed to the aerosol of a 5% solution of papain in the presence of cysteine and ethylenediamine-tetraacetic acid. Pulmonary emphysema in hamsters was observed after exposure to papain for two to three hours. There was no change with time in the severity of emphysema from the second through the fourth weeks after exposure to papain. Pathogenesis of pulmonary emphysema was discussed in relation to proteolysis of glycosaminoglycan-protein complex.

Animals

Corticosteroids in chronic bronchitis and pulmonary emphysema.

Chronic bronchitis and emphysema (chronic obstructive pulmonary disease [COPD]) represent a major health problem in this country. Corticosteroids have provided an important advance in the management of bronchial asthma, but the role of these drugs in the therapy for COPD has not been defined clearly. To gain further insight into this problem, an overview of the pharmacologic properties and mechanisms of action of corticosteroids on the cellular systems of the lung and a critical analysis of the 17 studies evaluating the efficacy of therapy with corticosteroids in COPD were done. There are several theoretic reasons why corticosteroids might be useful in treating COPD; however the majority of studies have not demonstrated a positive effect, yet individual patients have attained marked improvement. An objectively monitored, finite trial of therapy with corticosteroids in the patient with COPD who has worsening symptoms is warranted, as the benefit is high in responsive individuals and the risk is low in nonresponders.

Betamethasone

Persistent interstitial pulmonary emphysema: another complication of the respiratory distress syndrome.

Persistent interstitial pulmonary emphysema (PIPE) was observed in 22 infants during the neonatal period. All of the infants experienced respiratory distress during the first few days of life, and 21 of them were treated for the respiratory distress syndrome with artificial ventilation or oxygen or both. Ten infants developed a localized form of PIPE, with air-filled interstitial cysts measuring up to 3.0 cm in diameter confined to one or more lobes of lung. The involved segment of lung was resected in seven of these infants, all of whom survived. The remaining three died and autopsies were performed. A diffuse form of PIPE was observed in the other 12 infants. Numerous cysts that were predominantly small (less than 0.3 cm) were seen in all lobes of both lungs. These infants received high concentrations of oxygen for prolonged periods, resulting in bronchopulmonary dysplasia in 11 of the infants. All 12 infants died. PIPE is characterized histologically by air-filled interstitial cysts partially lined by multi-nucleated giant cells.

Cysts

[Alpha 1-anti trypsin-deficiency: combination of pulmonary emphysema and liver cirrhosis in infancy (author's transl)].

The combination of pulmonary emphysema and liver cirrhosis in early childhood is documented for the first time in a 31/2 year old girl with homozygous (ZZ) deficiency of a1-antitrypsin. Examination of relatives in the generation of parents and grand parents revealed 7 heterozygous (MS) and five normal members (MM). Lung function tests showed altered respiratory function in 4 out of these 7 heterozygous subjects. Measurement of trypsin inhibitory capacity in plasma gave a good correlation to the genotype, however determinations of a1-antitrypsin coincided with it to a lesser degree. A high trypsin inhibitory capacity was detected in the tears of the propositi, which was shown to be immunologically distinguishable from serum a1-antitrypsin. Similarly, antiprotease activity was demonstrated in nasal secretions. This too did not reflect the serum profile.

Adult

Unilateral pulmonary emphysema created by ligation of the left pulmonary artery in newborn puppies.

The left pulmonary artery was ligated in 7 puppies 12 to 24 hours after birth. All were followed by periodic chest roentgenograms. At 6 months of age, ventilatory spaces, split-lung function, and static compliances were determined. Bronchograms and arteriograms were obtained, and histopathology was studied. All animals demonstrated a decrease in left lung size with gross and microscopic changes typical of chronic emphysema. There was impressive bronchial artery hypertrophy. Oxygen consumption and static compliances in the left lungs were depressed. These marked alterations in maturation, as well as the degenerative changes, are believed to be related to an impairment in the nutritive circulation of the lung.

Animals

Further observations on luminal deformity and stenosis of nonrespiratory bronchioles in pulmonary emphysema.

In an endeavour to elucidate the anatomical basis for the increased resistance to airflow which characterises the most peripheral conducting air passages in pulmonary emphysema, lumina of nonrespiratory bronchioles of lungs with mainly centrilobular disease were assessed for two- and three-dimensional features by: (1) determination of percentage conformity of the lumina of individual bronchioles in histological sections to hypothetical planes through cylinders (ie, ellipses with the same areas and circumferences), and (2) comparison of luminal areas at regular intervals along bronchiolar longitudinal axes. The lumina of most nonrespiratory bronchioles from normal lungs conformed closely to their respective ellipses, thus corroborating previous observations that they are normally cylindroid. In contrast, there was a substantial excess of plane section deformities in the lumina of nonrespiratory bronchioles from the emphysematous specimens. The incidence of stenotic bronchioles (by both diameter and area determinations) was also greatly increased in emphysema. Since there was a strong positive association between such stenotic lesions and bronchiolar deformity, the latter was concluded to be a major factor in bronchiolar restriction. Furthermore, these characteristics seemed to have three-dimensional expression, for the lumina of stenotic bronchioles in emphysema were irregular in a longitudinal fashion.

Bronchi

Ventilation-perfusion scans in neonatal regional pulmonary emphysema complicating ventilatory assistance.

Two cases of ventilator-related neonatal lobar overexpansion with similar radiographic appearance, but probably different pathogenesis, are presented. In one infant, persistent interstitial lobar emphysema was confirmed by markedly decreased perfusion shown on scintigraphy; this information was of great value in predicting the beneficial effect of lobectomy. In the other case, ventilation and perfusion scans indicated functional value of the emphysematous lobe and correctly suggested conservative management. Radioisotope lung scans may provide valuable information regarding lung function in regional pulmonary emphysema associated with assisted ventilation in neonatal respiratory distress syndrome, and thus determine patient management.

Humans

[A study on glycosaminoglycans in a case of pulmonary emphysema (author's transl)].

The fraction of crude glycosaminoglycans was prepared from an emphysematous lung by means of proteolytic digestion, precipitation with ethanol and fractionation with CPC (cetylpyridinium chloride). The above fraction of crude glycosaminoglycans was then subjected to chromatography with a column of Dowex-1. Individual glycosaminoglycan species was identified based on the results of electrophoresis and on those of incubation with specific mucopolysaccharide-lyases. As a result, hyaluronic acid, chondroitin sulfate A (C), dermatan sulfate and heparan sulfate were detected. Quantitation of individual glycosaminoglycan species revealed that the ratio to total glycosaminoglycan of hyaluronic acid was smaller in the emphysematous than in the normal lung. The significance which can be attributed to the change in quantity of glycosaminoglycan of the lung was discussed in relation to pathogenesis of pulmonary emphysema.

Chondroitin

[Alpha 1-antitrypsin deficiency, liver cirrhosis and pulmonary emphysema (author's transl)].

It is well known that incidence of chronic obstructive lung disease in adult patients with alpha 1-antitrypsin deficiency (ATD) is high. Adult carriers of this genetic trait with cirrhosis of the liver, and also with fibrosis of the liver and hepatoma, have been reported. A causal relationship between ATD and liver lesions has been suspected. In most cases liver disease has been recognized at post morten, - in a few cases, however, intra vitam, when severe symptoms of the liver disease had become apparent. The case of a 59 year-old patient is reported with PIZZ-homozygous ATD, moderate pulmonary emphysema and with marked portal fibrosis and focal transition in cirrhosis of the liver without any sequelae. The clinical course has been rather benign so far.

Electrocardiography