Jack D. Fulmer

Unusual computed tomographic manifestations of benign metastasizing leiomyomas as cavitary nodular lesions or interstitial lung disease

The unusual computed tomographic manifestations of benign metastasizing leiomyomas diagnosed in two patients 3 1/2 and 6 years after hysterectomy for uterine fibroids are described. One showed multiple pulmonary nodules with a round or irregular air-filled cavity representing obstructive emphysema. The other showed interstitial lung disease with tumor cells spreading along alveolar septa, the vascular wall, and the bronchial tree. We consider such metastasizing tumors as low-grade leiomyosarcomas.

Dietary Fish Oil Inhibits Bleomycin-Induced Pulmonary Fibrosis in the Rat

Intratracheal bleomycin induces pulmonary fibrosis in experimental animals, but the mechanisms involved are poorly understood. Since altered levels of fatty acid metabolites are associated with bleomycin-induced lung injury, we examined the effects of a change in dietary fat on bleomycin-induced fibrosis. Previously we have shown that an essential fatty acid-deficient diet can reduce the severity of bleomycin-induced pulmonary fibrosis. The present study examined the effect of replacement of usual dietary fat with menhaden oil, rich in eicosapentaenoic acid, on the development of pulmonary fibrosis. Weanling rats were raised on a standard laboratory diet or a diet consisting of a fat-free powder to which was added 25% (w/w) of menhaden oil. After 8 weeks of feeding, the animals received either 1.5 units of bleomycin or an equivalent volume of saline intratracheally. In animals receiving the laboratory diet, bleomycin treatment produced a 44% increase in total lung protein content when compared to saline-treated controls (p less than 0.001) and a 77% increase in total lung hydroxyproline content (p less than 0.01). In contrast, bleomycin-treated animals receiving the menhaden oil diet had only small increases, which did not reach statistical significance, in protein and hydroxyproline content in the lung. Bronchoalveolar lavage cellularity did not differ among the treatment groups, but the percentage of lavage macrophages was slightly diminished in bleomycin-treated animals receiving the laboratory diet. Cellular differentials of lavage fluid did not differ significantly between bleomycin- and saline-treated animals receiving the menhaden oil diet. Bleomycin-induced histologic changes, quantitated by morphometric analysis, were significantly reduced with the menhaden oil diet. We conclude that a diet rich in eicosapentaenoic acid can significantly ameliorate bleomycin-induced pulmonary fibrosis, possibly via alterations in eicosanoid metabolism.

Experimental granulomatous lung disease in guinea pigs. Morphology and collagen analysis.

Chronic granulomatous lung disease was produced in immunized guinea pigs using aerosol exposure to pigeon serum at intervals of four weeks. Initially, animals developed a hemorrhagic alveolitis with polymorphonuclear leukocytes. After the second exposure, animals had a mononuclear alveolitis with ill-defined granulomata. Animals sacrificed after the third or fourth aerosol exposure had well-defined granulomata with varying degrees of interstitial fibrosis. Chemical estimates of total lung collagen showed increased lung collagen after the third and fourth exposure. Whereas animals sacrificed within one week after the second or third exposure had no increase in collagen concentration, animals sacrified 4 weeks after these exposures did. There was also a correlation between the morphologic and chemical estimates of lung collagen. These data suggest that repeated aerosol exposure of guinea pigs to a soluble antigen at intervals can result in chronic granulomatous lung disease that is characterized by morphologic and chemical increases in lung collagen. This model may be of value in defining immune and connective tissue alterations in granulomatous lung disease.

Modulation of the development of bleomycin-induced fibrosis by deferoxamine☆

Bleomycin is an antineoplastic compound which produces a time- and dose-dependent pulmonary fibrosis. The mechanisms which cause this fibrosis are not known. The ability of bleomycin to produce oxygen radicals in the presence of iron and molecular oxygen appears to be related to the fibrosis. Previous studies, which have examined single time points utilizing the ferric ion chelator deferoxamine and iron-deficient diets, suggest that iron plays a central role in bleomycin-induced pulmonary fibrosis. Therefore, the present study was designed to determine the effects of deferoxamine on the development of bleomycin-induced pulmonary fibrosis. Deferoxamine pretreatment and daily injections resulted in a significant reduction in lung collagen content and lung lipid peroxidation 21 days after intratracheal bleomycin compared with bleomycin treatment alone. In addition deferoxamine treatment significantly inhibited lung DNA increases at 4, 7, and 14 days after bleomycin treatment compared with bleomycin treatment alone. These data indicate that deferoxamine treatment reduces the development of bleomycin-induced pulmonary fibrosis in the later phase. The mechanism might be by the prevention of iron-catalyzed, free-radical formation and modulation of some cellular functions.

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 lungs 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.

Effects of dietary fats on bleomycin-induced pulmonary fibrosis

Bleomycin treatment has been used for the experimental induction of pulmonary fibrosis, but the mechanisms involved are poorly understood. Since alterations in the levels of certain fatty acid metabolites have been associated with bleomycin-induced lung injury, we examined the effects of different dietary fats on the development of bleomycin-induced pulmonary fibrosis. Weanling rats were raised on standard laboratory feed or a diet consisting of a fat-free powder to which was added either coconut oil or beef tallow (25% w/w). After 8 weeks of feeding, animals received either 1.5 units bleomycin or an equivalent volume of saline intratracheally. Bleomycin treatment resulted in significant increases in total lung hydroxyproline content in the groups fed the standard lab diet (p less than 0.001) and beef tallow diet (p less than 0.001), but not in the group receiving the coconut oil diet. Furthermore, the lung hydroxyproline content in bleomycin-treated animals was less with the beef tallow diet compared with standard lab feed (p less than 0.05). Bleomycin treatment resulted in an increase in thiobarbituric acid-reactive products, an index of lipid peroxidation, in lungs from animals fed the standard lab diet, but not in the other diet groups. The percentage of diseased lung, as determined by morphometric analysis, was increased in bleomycin-treated animals from all diet groups (p less than 0.05). We conclude that alterations in dietary fats can reduce the severity of pulmonary fibrosis resulting from bleomycin treatment. Possible mechanisms for this effect include alterations in eicosanoid metabolism or changes in immune or effector cell function.