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Biomedical subjects

J D Fulmer

Publications and source records attributed to J D Fulmer.

At least 37 records · Page 2Linked to original sources
PubMed1985

The effect of bleomycin on lung metabolism of prostaglandin E2 in hamster.

Lung is a major site of prostaglandin synthesis and degradation. One site of metabolism has been shown to be the endothelial cell. Metabolism of prostaglandins has been shown to be influenced by both physiological and pathological mechanism. Furthermore, it has been suggested that a relationship might exist between pulmonary disease and the lung's ability to synthesize and/or degrade prostaglandins. Therefore, we evaluated if bleomycin-induced fibrosis, a model of human pulmonary fibrosis, affects the ability of lung to metabolize prostaglandins. Single pass metabolism of prostaglandin E2 was evaluated in an isolated, perfused and ventilated lung of hamsters at 5 and 500 nM concentrations 4,7,14,21 and 28 days after intratracheal bleomycin. The metabolism of prostaglandin E2 was not changed at the 5 nM level, but was significantly decreased at 500 nM level on day 14 and day 28 after intratracheal bleomycin. The results suggest that intratracheal bleomycin causes alterations in prostaglandin metabolism; the mechanism(s) is unknown but may be related to endothelial cell damage and possible changes in alveolar-capillary surface area.

Animals↗
PubMed1985

The effect of endotoxin on bleomycin-induced lung fibrosis in the rat.

Bleomycin is a commonly used antineoplastic agent which produces dose- and time-dependent pneumonitis and fibrosis in humans. The mechanism of bleomycin-induced lung injury is uncertain. However, current data shows that bleomycin can generate reactive oxygen species such as superoxide and hydroxyl radicals. We therefore investigated whether intraperitoneal (i.p.) injection of endotoxin, a protectant for hyperoxia, could modulate the biochemical and morphological estimates of bleomycin-induced lung fibrosis in rats. However, pretreatment with multiple i.p. injections of endotoxin, combined with intratracheal bleomycin instillation, resulted in increased lung collagen content compared to bleomycin treatment alone and controls. Furthermore, morphological estimates of the severity of lung lesions present in the endotoxin-bleomycin treatment group were increased when compared with saline and endotoxin control lung lesions. These data indicate, in the current study design, that endotoxin did not reduce, but instead increased the severity of bleomycin-induced pulmonary fibrosis in rats. The mechanism for this increase in fibrosis may be the result of pre-existing endotoxin-induced cell injury.

Animals↗
PubMed1985

The effect of deferoxamine on bleomycin-induced lung fibrosis in the hamster.

Bleomycin is a commonly used antineoplastic compound that can produce a dose- and time-dependent pneumonitis and fibrosis in humans. The mechanism of bleomycin-induced fibrosis is not known. However, current data suggest that the production of oxygen radicals by way of a ferrous ion-molecular oxygen mechanism might be related to the pulmonary fibrosis. Therefore, we evaluated the possibility that parenterally administered deferoxamine, an iron chelating compound, could modulate the morphologic and biochemical estimates of bleomycin-induced lung fibrosis in hamsters. Deferoxamine pretreatment and daily injection for 21 days after intratracheally administered bleomycin resulted in a 33% reduction in lung collagen accumulation compared with that after bleomycin treatment alone. However, fibrosis was still present in the bleomycin-deferoxamine group; the animals showed a 142 and 150% increase in lung collagen compared with that in saline- and deferoxamine-treated control animals, respectively. Morphologic estimates of the severity of fibrosis in the bleomycin-deferoxamine treatment group were reduced when compared with the bleomycin treatment group alone, but was increased compared with saline- and saline-deferoxamine-treated control animals. These data indicate that deferoxamine treatment reduces the severity of bleomycin-induced pulmonary fibrosis in hamsters. The mechanism might be by the prevention of iron-catalyzed, free-radical formation.

Animals↗
PubMed1984

Corticosteroid therapy in asthma.

Corticosteroids are useful in the treatment of both allergic and idiosyncratic asthma. Although the mechanisms of corticosteroid action in asthma are poorly understood, several possible sites of action have been proposed. Corticosteroids alter the cellular and vascular inflammatory response to bronchial injury, affect catecholamine action on airways, and alter the production of eicosanoids, all of which aid in the resolution of bronchospasm in asthmatic patients. Corticosteroids should only be used for the treatment of asthma after therapeutic levels of methylxanthines and beta agonists have been achieved. Although the optimal doses of corticosteroids in asthma have not been defined, guidelines exist to aid in therapy. In the treatment of status asthmaticus, the intravenous route of administration is preferable. Short courses of corticosteroids may be useful in the treatment of chronic asthma. When long-term corticosteroid therapy is the only option for control of bronchospasm, alternate-day and/or aerosolized corticosteroids are preferable to daily corticosteroids and are associated with fewer side effects. Corticosteroids are useful in the pregnant asthmatic patient when bronchospasm cannot be controlled with bronchodilators. The major risk to the fetus in pregnant asthmatics is hypoxia from uncontrolled bronchospasm, and not from therapy. However, the lowest possible dose of systemic corticosteroids needed to control symptoms, with or without the use of aerosolized corticosteroids, is recommended. All asthmatics who have needed systemic or aerosolized corticosteroids within 6 months prior to surgery should receive preoperative and post-operative corticosteroid therapy. For patients not usually on systemic corticosteroids, conversion to oral prednisone, with a rapid taper is recommended. Side effects from short-term corticosteroid therapy are minimal, with hyperglycemia and psychosis being the major concerns. Long-term steroid therapy has significant side effects, however, and use should be minimized. Suppression of the HPA axis is one of the most potentially dangerous side effects of corticosteroids, and therefore any patient who has been treated with corticosteroids for longer than 4 weeks should be evaluated for possible adrenal suppression.

Adrenergic beta-Agonists↗
PubMed1982

Giant cell arteritis presenting as interstitial lung disease.

A 58-year-old woman had a clinical history compatible with polymyalgia rheumatica but with an unexplained interstitial lung disease. Evaluation, including biopsy specimens of temporal artery, lung, and gastrocnemius muscle, was consistent with giant cell arteritis. This case identifies giant cell arteritis as a cause of interstitial lung disease.

Bronchi↗
PubMed1982

An introduction to the interstitial lung diseases.

The interstitial lung diseases are a heterogeneous group of disorders that have similar clinical, roentgenographic, and physiologic features. The histopathology of most is characterized by an alveolitis and alveolar septal fibrosis. Current concepts are that connective tissue alterations are preceded and caused by the alveolitis. Clinicopathologic correlative data indicate that patients with an active alveolitis with minimal fibrosis are most likely to respond to treatment. Those patients with minimal alveolitis and severe fibrosis are unlikely to respond to treatment. Although lung biopsy is the standard for assessing the severity of alveolitis, chest roentgenograms and pulmonary function testing can be useful in some diseases. Recently, gallium lung scanning and bronchoalveolar lavage have emerged as promising monitors of disease activity. Gallium scans appear to be useful, but additional studies are needed. Although bronchoalveolar analysis will probably be a valuable aid in managing patients with interstitial disease, it cannot be recommended in the routine evaluation of these patients.

Bronchi↗
PubMed1981

Hereditary emphysema in the tight-skin (Tsk/+) mouse.

The tight-skin (Tsk/+) mouse represents an autosomal dominant mutation characterized by increased thoracic size, large lungs, and a variety of abnormalities of loose subcutaneous connective tissue, cartilage, tendon, and bone. Because an increase in the size of the lung and thorax may result from destruction of alveolar walls and a loss of elastic recoil of the lung, the present study was undertaken to determine if the Tsk/+ mouse exhibits morphologic and physiologic characteristics of emphysema. In contrast to the lungs of normal mice, examination of the lungs of Tsk/+ mice by light and scanning electron microscopy revealed generalized enlargement of air spaces with numerous subpleural cysts and scattered bullae. In addition, many alveolar walls were either markedly thinned or broken and there was an increase in the number and size of the pores of Kohn. Consistent with these morphologic observations, the lungs of the Tsk/+ mice also exhibited physiologic characteristics consistent with emphysema. Compared to the lungs of normal mice, the lungs of Tsk/+ mice had a markedly increased total lung capacity of (1.8 +/- 0.1 ml versus 3.3 +/- 0.1 ml, p less than 0.001); compliance (0.077 +/- 0.006 ml/cm H2O versus 0.345 +/- 0.025 ml/cm H2O, p less than 0.001), and specific compliance (4.23 +/- 0.34% TLC/cm H2O versus 10.64 +/- 1.01% TLC/cm H2O, p less than 0.001). These findings suggested that the Tsk/+ mouse is a genetically determined model of emphysema that may be useful in determining the pathogenesis of destructive lung disease.

Animals↗
PubMed1980

Functional correlates of lung involvement in Wegener's granulomatosis. Use of pulmonary function tests in staging and follow-up.

To examine the usefulness of pulmonary function testing in the clinical management of patients with Wegener's granulomatosis, 22 subjects with biopsy proved disease were evaluated using routine functional parameters. Although reduced lung volumes and diffusing capacity occurred frequently, the most common abnormality was in obstruction to airflow. Comparison of these functional parameters with roentgenographic and clinical findings revealed that reduced lung volumes were useful in detecting focal infiltrates, mass or cavitary lesions and diffuse interstitial involvement whereas airflow measurements were useful in detecting focal large airway lesions. In people with evidence of limitation of airflow, respiratory complications frequently developed in the form of acute tracheal obstruction of lobar collapse. In addition, serial evaluation of lung function during treatment revealed that although in most patients lung volumes and airflow obstruction improved or stabilized, a reduction of diffusing capacity was common. These studies suggest that routine pulmonary function testing may be a useful tool in the staging of patients with Wegener's granulomatosis and in following responses to therapy.

Adult↗