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Biomedical subjects

V J Ferrans

Publications and source records attributed to V J Ferrans.

At least 271 records · Page 15Linked to original sources
PubMed1983

Reduction by ICRF-187 of acute daunorubicin toxicity in Syrian golden hamsters.

Administration of a single dose of daunorubicin (25 mg/kg) to Syrian golden hamsters caused a marked decrease in food consumption and body weight and death within 1 to 3 weeks. The severity of acute daunorubicin toxicity was reduced by pretreatment with ICRF-187 at doses of 12.5 mg/kg or greater. Although most animals pretreated with 12.5 to 50 mg ICRF-187/kg were alive after 5 weeks, body weight was below control levels. Animals pretreated with 100 mg ICRF-187/kg were the only group able to regain initial weight loss and increase body weight above the preinjection control level. Different degrees of protection were observed when the 100 mg/kg dose of ICRF-187 was given at various times before and after daunorubicin. Significant numbers of animals (45%) survived when ICRF-187 was given 48 h before daunorubicin. Optimal survival was observed when 100 mg ICRF-187/kg was given from 3 h before to 3 h after daunorubicin. The protective effect of ICRF-187 was lost when it was administered more than 6 h after daunorubicin. The lethal effects of high doses of daunorubicin may be due to profound gastrointestinal toxicity. Alterations in the heart, liver, or kidneys did not appear to be of sufficient magnitude to be responsible for the lethality in the hamsters. In contrast, marked histopathological changes were found throughout the entire length of the gastrointestinal tract from the colon to the tongue. ICRF-187 appears capable of altering daunorubicin toxicity on this tissue.

Animals↗
PubMed1983

Prevention of chronic doxorubicin cardiotoxicity in beagles by liposomal encapsulation.

Antitumor drugs such as doxorubicin have been encapsulated into liposomes as a means of enhancing activity and reducing toxicity. The present study was initiated to determine whether chronically administered liposome-encapsulated doxorubicin would be less toxic than the free drug. Doxorubicin was prepared in positively charged cardiolipin liposomes, and 1.75 mg/kg was given i.v. to each of five beagles. A second group received the free drug at 1.75 mg/kg. Additional animals received i.v. injections of either doxorubicin-free liposomes or 0.9% NaCl solution. All substances were given at 3-week intervals, and the experiment ended 1 week after the seventh injection (total dose, 12.25 mg/kg). A temporary reduction in food consumption was noted during the first few days after the administration of either form of doxorubicin. The effect was more severe in the dogs given free doxorubicin, and body weight decreased significantly only in this group of animals. Three dogs given free doxorubicin died or were killed before the end of the study because they were in poor condition. Lesions consisting mainly of vacuolization and myofibrillar loss were noted in the hearts of all five dogs given free doxorubicin. The severity of the lesions ranged from 2 to 4 (average, 3.4). In contrast, no abnormalities were found in any of the hearts from dogs given the liposomal doxorubicin. The most obvious general toxic effect caused by administration of free doxorubicin was alopecia, which was entirely prevented when doxorubicin was encapsulated into liposomes. At the dosage regimen utilized, liposomal doxorubicin and free doxorubicin exerted comparable degrees of bone marrow suppression. Thus, liposomal encapsulation of doxorubicin decreased cardiac and other toxic effects elicited by free doxorubicin. Whether this advantage can be translated into effective antineoplastic activity will need further evaluation.

Amines↗
PubMed1983

Clinical, clinicopathologic, and pathologic alterations in acute monensin toxicosis in cattle.

Twenty beef calves weighing approximately 180 kg were allotted to 3 groups. In group A, 6 calves were given 25 mg of mycelial monensin/kg of body weight orally and were evaluated at 1, 2, and 4 days for clinical, ECG, clinicopathologic, and pathologic alterations. In group B, 7 calves were given a single dose of monensin (40 mg/kg) and 5 were given a 2nd 40 mg/kg dose on day 7; calves were evaluated at days 1, 2, 4, 7, 8, 9, and 11. In group C, 2 calves served as controls. Monensin-treated calves developed anorexia, diarrhea, and lethargy after day 1. One group B calf died on day 7 with lesions of congestive heart failure. Electrocardiographic abnormalities were not observed in group A calves; in group B, prolongation of Q-T and QRS intervals occurred from days 2 to 11 and first degree heart block was seen from days 7 to 11. Clinicopathologic alterations included: increased serum activities of aspartate aminotransferase and creatine kinase in group B calves after day 2; decreased serum K+, Na+, and Ca2+ concentrations in both groups, and postdosing occurrence of leukocytosis. Calves were euthanatized sequentially and the lesions of monensin toxicosis were present in the heart, skeletal muscles, and rumen in groups A and B. Disseminated pale yellowish-brown areas of necrosis were present in the ventricular myocardium of 6 of 12 group B calves. Gross lesions were not present in the skeletal muscles or rumen. Microscopically, the myocardial and skeletal muscular lesions were characterized by sarcoplasmic vacuolation from mitochondrial swelling and lipid accumulation in calves killed after day 1 in groups A and B, and by myocardial necrosis with contraction bands, but without calcification, in group B calves killed by day 4. Acute rumenitis was present in groups A and B calves. Myotoxic effects of monensin may be related to its action as an ionophore producing altered intracellular ion concentrations and initiating degeneration and necrosis in striated muscle fibers.

Acute Disease↗
PubMed1983

Congestive cardiomyopathy induced in ducklings fed graded amounts of furazolidone.

Newly hatched male White Pekin ducklings (n = 119) were allotted to 7 groups of 17 each and fed furazolidone (FZ) at dose levels of 0, 100, 250, 500, 750, 1,000, and 1,250 mg/kg of feed for 4 weeks. The frequency and severity of clinical signs of FZ toxicosis, including growth retardation, ascites, and mortality, were dose related. At necropsy, the affected ducklings had ascites, hydropericardium, and biventricular dilatation. The frequencies of cardiomyopathy, ascites, and mortality, respectively, for the several dose levels of drug were as follows: 0, 100, and 250 mg of FZ/kg of feed--0%, 0%, 0%; for the 500 mg/kg level--35%, 12%, 0%; for the 750 mg/kg level--100%, 53%, 18%; for the 1,000 mg/level--79%, 57%, 57%; and for the 1,250 mg/kg level--33%, 20%, 73%. Ducklings with FZ-induced congestive cardiomyopathy had decreased left ventricular free wall and ventricular septal thickness, increased left ventricular chamber diameter, increased left ventricular dilatation score, decreased absolute heart weight, and increased relative heart weight. Cardiac histopathologic changes were minimal; some ducklings had myocytolysis. Liver and lungs were congested. Furazolidone-induced cardiomyopathy in ducklings offers a model for studies of congestive cardiomyopathy in a species that is free from the hereditary cardiomyopathy ("round heart disease") seen in turkeys.

Animals↗
PubMed1983

Hypersensitivity pneumonitis in man. Light- and electron-microscopic studies of 18 lung biopsies.

Light- and electron-microscopic changes produced by hypersensitivity pneumonitis were analyzed in open lung biopsies taken from 18 patients with chronic forms of the disease. The main changes observed were: alveolitis (both luminal and mural), granulomas, intraalveolar buds, and interstitial fibrosis. The cells infiltrating the alveolar walls were mainly lymphocytes. Occasionally these lymphocytes presented irregularities in the contours of the nuclear membranes and resembled Sézary cells. In one patient, a few lymphocytes were found that resembled "hand-mirror" cells. Intraalveolar macrophages often had a foamy appearance. Granulomas, present in two-thirds of the patients, differed in several respects from those in sarcoidosis: they were smaller, more loosely arranged, and poorly limited; they had a higher content of lymphocytes; and they were located more frequently in alveolar tissue than in the vicinity of bronchioles and vessels. Intraalveolar buds, also present in about two thirds of the patients, were composed mainly of fibroblasts, myofibroblasts, and macrophages in a loose connective tissue that was rich in proteoglycan material. Capillaries and epithelial cells were rarely seen in buds. Alveolar buds appear to develop by a process of disruption of the epithelial lining layer, due to alveolitis, followed by intraalveolar exudation and by subsequent intraalveolar migration of connective tissue cells interacting with macrophages. Severe fibrotic and alveolar epithelial changes were observed in four patients; milder changes were frequent in most other patients. It is concluded that hypersensitivity pneumonitis usually has distinctive morphologic features; these may help to distinguish the resultant pulmonary fibrosis from that due to other causes.

Adult↗
PubMed1983

Furazolidone-induced congestive cardiomyopathy in ducklings: regression of cardiac lesions after cessation of furazolidone ingestion.

Newly hatched male White Pekin ducklings (n = 92) were allotted to 2 groups of 46 each and fed 750 mg of furazolidone (FZ)/kg of feed either for 8 weeks (group 1) or for 4 weeks followed by 4 weeks of no FZ intake (group 2). Regression of FZ-induced toxicosis was observed in ducklings of group 2 after cessation of FZ consumption, as evidenced by decreased mortality, progressive decrease in ascites, and increases in body weight gains. Necropsy of 8-week survivors revealed decreased frequency and severity of ascites in ducklings of group 2. The severity of FZ-induced cardiac alterations also was diminished, with a decrease in left ventricular dilatation score and an increase in absolute heart weights in 8-week survivors in group 2. Further evidence of regression of FZ-induced congestive cardiomyopathy after cessation of FZ ingestion was gained from development of intermediate cardiac damage severity scores and frequency and severity of ascites at necropsy in ducklings (previously studied) examined after 4 weeks of FZ feeding, compared with those found in group 1 (FZ 8 weeks) or in group 2 (FZ 4 weeks, no FZ 4 weeks) of the present study. Furazolidone-induced cardiac disease in ducklings offers an attractive model for studies of the pathogenesis of congestive cardiomyopathy and cardiac failure.

Animals↗
PubMed1983

Furazolidone-induced congestive cardiomyopathy in ducklings: myocardial ultrastructural alterations.

Newly hatched male White Pekin ducklings were fed furazolidone (FZ) at dosage of 750 mg/kg of feed for 4 weeks. Selected ducklings with advanced lesions of FZ-induced congestive cardiomyopathy were used for ultrastructural study of the myocardial alterations. Semithin sections of plastic-embedded blocks of myocardium from these dilated hearts revealed diffuse myocytolysis, characterized by pale sarcoplasm and lack of cross-striations in affected myocytes. Evidence of myocardial necrosis, inflammation, or fibrosis was not observed. Ultrastructural study revealed that the principal alteration in cardiac muscle cells was diffuse myofibrillar lysis. The sarcoplasm of affected myocytes had scattered masses of free thick and thin myofilaments, clumps of Z-band material, and accumulations of cytoskeletal filaments. Numerous polyribosomes were present in the areas of lysis of contractile material, as were other normal-appearing organelles. Myofibrillar lysis may have resulted from FZ-induced decreased synthesis, increased degradation, or disaggregation of contractile proteins. Ducklings with FZ-induced congestive cardiomyopathy offer an attractive model for studies of the biochemical and ultrastructural alterations of myofibrillar lysis and drug-induced cardiac failure.

Animals↗
PubMed1983

Furazolidone-induced congestive cardiomyopathy in ducklings: lack of protection from selenium, vitamin E, and taurine supplements.

Newly hatched male White Pekin ducklings (n = 108) were allotted to 6 groups of 18 each and were fed for 4 weeks diets containing 750 mg of furazolidone (FZ)/kg of feed either alone or with supplements of vitamin E (250 IU of dl-alpha-tocopheryl acetate/kg), selenium (2.5 mg as selenite/kg) or taurine (1%). Control groups were fed diets without FZ and with or without added taurine (1%). Ducklings in the 4 FZ-fed groups had retarded growth, mortality, ascites, and cardiac alterations of congestive cardiomyopathy. Supplements of vitamin E, selenium, or taurine did not protect against the development of the cardiac and extracardiac alterations of FZ toxicosis. These findings could indicate that the development of FZ-induced congestive cardiomyopathy is not mediated by low tissue concentrations of selenium, vitamin E, or taurine.

Animals↗
PubMed1982

Anthracycline-induced histamine release from rat mast cells.

Comparisons were made of the ability of doxorubicin, daunorubicin, rubidazone and aclacinomycin A to release histamine from rat peritoneal mast cells. Preliminary in vitro experiments indicated that doxorubicin (10(-6) to 2.5 X 10(-4) M), in contrast to compound 48/80 and the calcium ionophore A23187, did not produce significant release under any condition tested when purified or unpurified rat mast cells were used. In in vitro experiments, released histamine was measured in the cell-free supernatant of peritoneal fluid of rats after intraperitoneal injection of the agents. The time course of doxorubicin-induced histamine release from the peritoneum was rapid, with maximal release occurring within 4 to 6 min. Dose-response curves of the 4 agents over the range 10(-5) to 3.3 X 10(-3) M revealed that all caused histamine release, with 10(-3) M concentrations of each causing maximal release of comparable magnitude to that produced by 9.5 X 10(-6) M A23187. Treated mast cells recovered from the peritoneal cavity showed degranulation and vacuolization when examined by electron microscopy. Increased vascular permeability by the Evans-blue test was also noted with all 4 agents, and zones were of comparable size after injection of the highest concentration of each agent. The results indicate that in vivo, doxorubicin, daunorubicin, rubidazone and aclacinomycin A cause a rapid release of histamine from rat mast cells and an increase in vascular permeability in rat sin. There also appeared to be a reasonable correlation between the blueing reaction and histamine release in the peritoneal cavity in that the doses that did not cause skin blueing also failed to cause histamine release. The lack of histamine release by doxorubicin from mast cell preparations in vitro suggests that alterations to the doxorubicin molecule or the presence of other critical substances may be necessary for this activity to commence.

Aclarubicin↗
PubMed1982

Role of alveolar macrophages in asbestosis: modulation of neutrophil migration to the lung after acute asbestos exposure.

After intratracheal injection of short chrysotile asbestos fibres in guinea-pigs an intense neutrophil alveolitis was observed within three days. Evaluation by bronchoalveolar lavage of the inflammatory and immune effector cells producing the alveolitis by three days showed an increased proportion of polymorphonuclear leucocytes, which comprised 21% +/- 3% of the total leucocytes compared with 9% +/- 2% for the controls (p less than 0.05), persisting for at least six weeks (after which time the polymorphonuclear leucocytes comprised 28% +/- 2% compared with 7% +/- 1% for the controls: p less than 0.05). One mechanism by which asbestos fibres may cause polymorphonuclear leucocytes to be attracted to the alveolar structures is by induced release of neutrophil chemotactic factor by alveolar macrophages. When exposed in vitro to short or intermediate chrysotile fibres or amosite or crocidolite fibres guinea-pig alveolar macrophages released appreciable amounts of neutrophil chemotactic factor. The release of this chemotactic factor was augmented when the asbestos fibres had been previously exposed to normal serum. The chemotactic factor was lipid soluble, and was similar to the neutrophil chemotactic factor spontaneously released by alveolar macrophages recovered from guinea-pigs exposed in vivo to short chrysotile fibres. These observations suggest that alveolar macrophages may play an important part in the early stages of asbestosis by modulating the migration of neutrophils to the lung.

Animals↗
PubMed1982

NIH conference. The idiopathic hypereosinophilic syndrome. Clinical, pathophysiologic, and therapeutic considerations.

The idiopathic hypereosinophilic syndrome (HES) represents a heterogeneous group of disorders with the common features of prolonged eosinophilia of an undetectable cause and organ system dysfunction. Fifty patients with the idiopathic HES were studied over 11 years of the National Institutes of Health. Multiple organ systems were involved; bone marrow hypereosinophilia was common to all patients, but the most severe clinicopathologic involvement was of the heart and nervous system. Postmortem gross pathologic examination of the hearts of patients with idiopathic and nonidiopathic HES suggested that the common mechanism of cardiac disease is the eosinophilia. Endomyocardial biopsy findings showed that the endothelial cells in the endocardium and of the microvasculature were the primary targets of the tissue damage. This damage initiates thrombosis; endocardial fibrosis and restrictive endomyocardopathy may follow. In-vitro culture of circulating eosinophil colony-forming units showed some normal studies, some studies showing increased progenitor cells committed to eosinophil development, and others showing an excess production of eosinophil colony-stimulating factor. Chemotherapy to lower the eosinophil counts has resulted in marked improvement of HES prognosis, as have agressive medical and surgical approaches to cardiovascular complications.

Cardiomyopathies↗
PubMed1982

Effect of thyroid hormone supplementation on chronic doxorubicin (adriamycin)-induced cardiotoxicity and serum concentrations of T3 and T4 in dogs.

Chronic doxorubicin (adriamycin; ADR) intoxication was produced in Beagle dogs by weekly IV injections (1 mg/kg of body weight) for 20 weeks (cumulative dose 400 mg of ADR/m2). Group A (5 dogs) were given ADR only; group B (5 dogs), ADR and daily supplements of 0.5 mg of L-thyroxine (T4) (twice the recommended maintenance dose); and group C (5 dogs), ADR and 2.0 mg of T4 daily (8 times the recommended maintenance dose). The control group D (5 dogs) was given 0.5 mg of T4 daily. The ADR-induced cutaneous lesions (alopecia and melanosis), body weight loss, hematologic alterations, and myocardial microscopic and ultrastructural alterations (sarcoplasmic vacuolation and myocytolysis) were present with equal severity in the 3 ADR-treated groups, with or without T4 supplements. Six of the 15 ADR-treated dogs died during the study: 3 dogs had pneumonia, 1 dog had no established cause of death, and 2 dogs (from group C) had lesions of congestive cardiac failure. All ADR-treated dogs given a cumulative dose of 340 mg of ADR/m2 or more had characteristic myocardial histopathologic alterations, but 2 dogs that died after they were given only 140 or 260 mg of ADR/m2 had no microscopic evidence of myocardial damage. Low serum triiodothyronine (T3) concentrations were present in ADR-treated dogs after 28, 56, 84, 112, and 140 days and were attributed to faulty extrathyroidal conversion of T4 to T3. Serum T4 concentrations were high in dogs given 2 mg of T4/day (group C) after 28, 56, 84, and 112 days, but were low terminally as those dogs became debilitated from chronic ADR toxicosis. Unusual clinical signs or cardiac alterations of hyperthyroidism did not develop in the dogs given T4 supplements (groups B, C, and D). Our findings indicate that supplements of T4 do not alter the development of the cardiac and extracardiac lesions of chronic ADR toxicosis in dogs and indicate that the ADR-induced lesions probably are not mediated via hypothyroidism.

Alopecia↗
PubMed1982

Structure of alveolar epithelial cells in patients with fibrotic lung disorders.

Ultrastructural studies were made of the types of alveolar epithelial cells in fibrotic lungs from 34 patients, including 20 with idiopathic pulmonary fibrosis, five with collagen-vascular diseases, six with sarcoidosis, one with lymphangioleiomyomatosis, one with histiocytosis X, and one with chronic eosinophilic pneumonia. In 28 patients, proliferation of type II alveolar epithelial cells was recognized on the basis of lamellar bodies in the cytoplasm, microvilli in the luminal surface, focal microfoldings of the basal plasma membrane, close interaction with underlying mesenchymal cells, and unilayered arrangement. Two types of cuboidal epithelial cells were recognized and were considered to be derived from bronchiolar basal cells (type A cuboidal cells) and from cuboidal cells in respiratory bronchioles (type B cuboidal cells). Type A cuboidal cells frequently contained large numbers of cytoskeletal filaments, and their basal plasma membranes possessed hemidesmosomes in close association with anchoring fibrils. Type B cells lacked hemidesmosomes and anchoring fibrils, Proliferation of either or both types of cuboidal cells was found in 30 patients. In 10 patients (average degree of fibrosis = 3.5 on a scale of 0 to +4), the proliferation involved type A cells; in 10 other patients (average degree of fibrosis = 2.5), type B cells in nine patients (average degree of fibrosis = 3.4), both type A and type B cells; in one patient cuboidal cells were identified only by light microscopy. In 17 patients, proliferating cuboidal cells formed foci of epithelial pseudostratification. Type II alveolar epithelial cells did not participate in the process of multilayering. Thus, type II alveolar epithelial cells and two types of cuboidal epithelial cells are sources of epithelial renewal in damaged alveoli in fibrotic lungs. Type II cells proliferate mainly in areas of less severe degrees of fibrosis; cuboidal cells become the main source of epithelial renewal in areas of very severe lung damage.

Biopsy↗