"Comparative study of calcification in the T6-treated and standard Hancock-I porcine xenografts: experimental study in weanling sheep".
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Animals↗
Biomedical subjects
V J Ferrans
Publications and source records attributed to V J Ferrans.
Interobserver variability in the pathologic interpretation of endomyocardial biopsy results.
Controversy exists over the role of endomyocardial biopsy in evaluating patients with dilated cardiomyopathy, particularly in detecting myocarditis and in assessing prognosis. Interobserver variability, if high, could explain conflicting reports. To assess this possibility, we submitted biopsy specimens from 16 patients with dilated cardiomyopathy to seven cardiac pathologists. The same slides were independently reviewed by each and assessed for fibrosis, hypertrophy, nuclear changes on a 0 to 3+ scale, mean lymphocyte count per high-power field, and myocarditis. The prevalance of significant fibrosis ranged from 25% to 69%, hypertrophy from 19% to 88%, nuclear changes from 31% to 94%, and abnormal lymphocyte count from 0 to 38%. One or more pathologists diagnosed definite or possible myocarditis in 11 of the 16 patients. Of these 11 patients, three pathologists agreed about three and two pathologists agreed about five. Myocarditis was diagnosed by a single pathologist in three cases. We conclude that interobserver variability is high in interpreting biopsy specimens from patients with dilated cardiomyopathy and that quantitative and standardized methods are needed to increase diagnostic consistency.
Adult↗
Susceptibility to experimental interstitial lung disease is modified by immune- and non-immune-related genes.
To evaluate the concept that genetic factors modulate susceptibility to agents that cause interstitial lung disease, animal models of interstitial lung disease caused by bleomycin or by inhalation of organic particulates (ovalbumin or bovine gamma globulin after specific immunization) were studied in strains of mice with different genetic backgrounds. Because immune processes have been implicated in modulating the susceptibility to agents that cause interstitial lung disease, we also compared congenic, resistant strains (strains with the same background but with different H-2 haplotypes) for their sensitivity to the same agents. In bleomycin-induced disease, the degree of lung disease was different in some of the different strains of mice and, in some strains, was related to H-2 locus genes since all strains with H-2b haplotypes were high responders, whereas most of the strains with H-2a, H-2d, and H-2k haplotypes were low responders. However, some of the strains of mice with the same H-2 haplotype but otherwise different genetic backgrounds had different responses to bleomycin, suggesting that there is also a role for non-H-2 genetic factors in modulating the response to this experimental interstitial lung disease. In the ovalbumin-induced lung disease model, as in bleomycin-induced lung disease, there were different strain susceptibilities: 2 of the 3 strains in the H-2b group were high responders, as was 1 of the 3 strains in the H-2k group. Interestingly, evaluation of the congenic, resistant strains showed that on the same backgrounds the H-2-related genes were able to modulate the degree of lung lesions.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Acute tropical pulmonary eosinophilia. Characterization of the lower respiratory tract inflammation and its response to therapy.
Although acute tropical pulmonary eosinophilia (TPE) is well recognized as a manifestation of filarial infection, the processes that mediate the abnormalities of the lung in TPE are unknown. To evaluate the hypothesis that the derangements of the lower respiratory tract in this disorder are mediated by inflammatory cells in the local milieu, we utilized bronchoalveolar lavage to evaluate affected individuals before and after therapy. Inflammatory cells recovered from the lower respiratory tract of individuals with acute, untreated TPE (n = 8) revealed a striking eosinophilic alveolitis, with marked elevations in both the proportion of eosinophils (TPE 54 +/- 5%; normal 2 +/- 5%; P less than 0.001) and the concentration of eosinophils in the recovered epithelial lining fluid (ELF) (TPE 63 +/- 20 X 10(3)/microliter; normal 0.3 +/- 0.1 X 10(3)/microliter; P less than 0.01). Importantly, when individuals (n = 5) with acute TPE were treated with diethylcarbamazine (DEC), there was a marked decrease of the lung eosinophils and concomitant increase in lung function. These observations are consistent with the concept that at least some of the abnormalities found in the lung in acute TPE are mediated by an eosinophil-dominated inflammatory process in the lower respiratory tract.
Adult↗
Morphological study of the transverse-axial tubular system (TAxTS) in rat heart using ferrocyanide-osmium method and thick sectioning.
The structure of the transverse-axial tubular system (TAxTS) in ventricular and atrial myocytes of the rat heart was investigated by examining thick (as much as 0.2 micron) and thin sections stained by the ferrocyanide-osmium method. Ventricular myocytes contain longitudinally and transversely oriented tubules which represent invaginations of the plasma membranes and form orderly latticeworks. These tubules are irregular in diameter and course tortuously. Dilated, triangular cisterns are often seen at the points of interconnections between longitudinal and transverse elements. The junctional sarcoplasmic reticulum forms 'couplings' with both transversely and longitudinally oriented TAxTS tubules, and a large proportion of the surface area of the TAxTS tubules is involved in such couplings. In atrial myocytes, the TAxTS tubules are poorly developed and pleomorphic, often with a beaded appearance, and show an irregular distribution from one cell to another and from one area to another within a given cell. The osmium-ferrocyanide stain reveals the TAxTS to be much more extensive than is evident from examination of routinely stained preparations.
Animals↗
Chloroquine-induced cardiomyopathy.
Biventricular hypertrophy and failure developed in two patients during treatment of systemic lupus erythematosus with chloroquine phosphate. In both patients, morphologic analysis of the myocardium, obtained by a right ventricular endomyocardial biopsy in one patient and at autopsy in the other, revealed accumulations of electron-dense concentric and parallel lamellae and curvilinear bodies within cardiac myocytes. These deposits were similar to those reported in chloroquine-induced skeletal myopathy and were considered to represent evidence of chloroquine-induced cardiotoxicity rather than a cardiovascular manifestation of the underlying disease. Clinical awareness and an endomyocardial biopsy specimen are necessary for the appropriate diagnosis of chloroquine-induced cardiomyopathy.
Adult↗
Juvenile polysaccharidosis with cardioskeletal myopathy.
Polysaccharidoses with ultrastructural features reminiscent of glycogenosis type IV, but without enzymatic correlation, have been observed in several adolescent and adult patients. Little is known of the clinical, pathologic, or biochemical nature of these disorders. We describe a patient with ultrastructural characteristics consistent with glycogenosis type IV, but with normal brancher enzyme activity in dermal fibroblasts and cardiac muscle. During life and at autopsy, electron microscopy revealed amylopectin-like polysaccharide deposits present in a wide variety of tissues. The polysaccharidosis of our patient and similar patients may be a variant of glycogenosis type IV with a yet to be defined enzymatic defect.
Biopsy↗
Evidence of myocyte hyperplasia in hypertrophic cardiomyopathy and other disorders with myocardial hypertrophy?
A review is presented of the mechanisms that mediate the increase in cardiac mass that occurs in patients with hypertrophic cardiomyopathy. This increase in mass is mediated by an increase in the total mass of the myocytes and the total mass of interstitial fibrous connective tissue. The increase in myocyte mass is the most important of these two components. However, it is not clear at the present time whether this increase is mediated not only by an increase in the size of the cells (hypertrophy), but also by an increase in the numbers of myocytes (hyperplasia) or by a combination of these two factors. Hyperplasia normally occurs during the prenatal phase of cardiac development and stops soon after birth, at which time hypertrophy becomes the main mechanism by which cardiac mass increases. Under certain circumstances, the ability of cardiac myocytes to synthesize DNA and undergo mitotic division can be restored; however, it is uncertain to what extent this results in complete cell division or only in either polyploidy or bi- or multinucleation. It is proposed that in hypertrophic cardiomyopathy, increased hyperplasia of cardiac myocytes occurs early in life and leads to permanently disturbed patterns of cardiac gross anatomy; it is then followed by a phase of progressive hypertrophy after the switch from hyperplastic to hypertrophic growth. It is possible that hyperplasia continues to occur after the usual time of this switch. It is also proposed that the increased number of layers of myocytes in the ventricular septum of patients with hypertrophic cardiomyopathy is a consequence of exaggerated hyperplasia during development.
Animals↗
Evaluation of explanted polyurethane trileaflet cardiac valve prostheses.
Morphologic, chemical, and hemodynamic studies were made of eight prototype polyurethane trileaflet cardiac valve prostheses that had been implanted in juvenile sheep for 17 to 21 weeks in the mitral position. Calcification of the polyurethane leaflet surfaces was the principal finding. Quantitative chemical analyses revealed calcium values with a mean of 42.7 +/- 21 mg/gm dry weight of leaflet. Morphologically, two distinct types of calcification were observed: One was associated with the polyurethane surface or the interface between the leaflet surface and microthrombi or fibrous sheaths; the other was characterized by calcification associated with degenerated cells within thrombotic material and the fibrous sheath. These morphologic findings were in accord with the results of hemodynamic performance studies indicating that these heart valve prostheses had become both stenotic and regurgitant.
Animals↗
Ultrastructural changes in inherited cardiac calcinosis of DBA/2 mice.
Cardiac dystrophic calcinosis, an inherited condition in DBA/2 mice, produced extensive calcific lesions in the right ventricular myoepicardium of affected mice. The morphogenesis of the cardiac alterations was evaluated by microscopic and ultrastructural studies. The initial event was necrosis and mineralization of subepicardial myocytes. Mineral deposits were seen as dense granular and spicular deposits in mitochondria only, mitochondria and adjacent sarcoplasm, or the entire sarcoplasm in necrotic myocytes. In mature myoepicardial calcific lesions, the remnants of necrotic myocytes were seen as scattered dense masses of mineralized debris with surrounding fibroplasia and occasional macrophages and giant cells. Male weanling DBA/2 mice (n = 135) were fed either a commercial diet adequate in selenium-vitamin E (Se-E) content, or a basal semipurified Se-E-deficient diet with or without silver acetate for 15, 20 or 25 weeks. Cardiac calcinosis severity seemed to increase in mice which developed concurrent Se-E deficiency. Cardiac calcinosis in the DBA/2 mouse is a useful model of cardiac calcification.
Animals↗
Dendritic cells with antigen-presenting capability reside in airway epithelium, lung parenchyma, and visceral pleura.
In this study, we identified a population of dendritic cells (DC) that exists throughout human and mouse pulmonary tissues, including the trachea, bronchi, alveoli, and visceral pleura. In human tissue, these DC were shown to be positive for HLA-DR and T200 antigens. In the mouse, the DC expressed not only Ia and the T200 antigen, but also Fc-IgG and C3bi receptors. Unlike alveolar macrophages, the DC were negative for nonspecific esterase staining and shared ultrastructural similarities with the DC described by Steinman (1), and with Langerhans' cells, even though they did not contain Birbeck granules. We were able to demonstrate that mouse pulmonary DC function in antigen presentation, as observed with the other DC. Thus, the respiratory tract contains DC that are capable of functioning in antigen presentation and that may be important in pulmonary immune responses.
Animals↗
Investigation of the immunological basis of halothane-induced hepatotoxicity.
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Animals↗
Pretreatment with ICRF-187 provides long-lasting protection against chronic daunorubicin cardiotoxicity in rabbits.
The long-term protective effect of ICRF-187 against chronic daunorubicin cardiotoxicity was examined. Rabbits were given 3.2 mg daunorubicin/kg, with or without pretreatment with 25 mg ICRF-187/kg, once every 3 weeks over an 18-week period (6 doses). The experiment was terminated 3 months after the last treatment. At this time, all seven rabbits given daunorubicin alone had evidence of myocardial alterations ranging from minimal (2 animals) to mild (5 animals). Pretreatment with ICRF-187 caused a significant reduction in both the incidence and the severity of cardiac lesions. Hearts from the majority (5 of 7) of animals given the combination of ICRF-187 and daunorubicin were normal; myocardial alterations were minimal in the remaining rabbits treated with ICRF-187. In previous studies ICRF-187 was found to cause a reduction in cardiotoxicity 1-3 weeks after the final anthracycline dose. The results of the present study demonstrate that pretreatment with ICRF-187 provides prolonged protection against the cardiomyopathy, as opposed to producing only a delay in the appearance of cardiac alterations.
Animals↗
Trypanosoma cruzi: ultrastructural changes produced by an anti-trypanosomal factor from Pseudomonas fluorescens.
Trypomastigotes and amastigotes of Trypanosoma cruzi exhibited distinct ultrastructural alterations when treated with an extracellular lytic substance (anti-trypanosomal factor) produced by Pseudomonas fluorescens. Marked swelling of the parasites and detachment of the plasma membrane from the subjacent cytoplasm were observed after 15 min of treatment. After 3 hr, the nucleus was extensively damaged, the kinetoplast was indistinguishable, the mitochondrion was markedly swollen, the cytoplasm was disrupted, and the plasma membrane showed extensive blebbing and focal loss of subpellicular microtubules. These changes were progressive, as shown by the occurrence of parasite ghosts after 10 hr. Amastigotes exhibited an extremely swollen mitochondrion with disrupted internal structure, widening of the perinuclear space, and blebbing of the external nuclear membrane. The kinetoplast, however, remained clearly discernible. The drugs used today in controlling Chagas' disease are toxic. Therefore, there is a need for new anti-trypanosomal agents such as the Pseudomonas fluorescens antibiotics. The observations described in this study indicate the potential chemotherapeutic usefulness of these compounds for this disease.
Animals↗
Acute rejection after cardiac transplantation: detection by interstitial myocardial pH.
Intramyocardial pH was assessed as a potential marker for clinical evaluation and treatment of acute rejection following cardiac transplantation. Fifteen cats underwent forty operative procedures. Following intra-abdominal heterotopic heart transplantation, serial laparotomies were performed in the early (days 0 to 2), intermediate (days 5 to 7), and late (days 7 to 16) postoperative periods. Rejection was assessed by serial clinical examinations, ECG analyses, B-mode echocardiography, histological and ultrastructural analyses, and measurements of interstitial myocardial pH. Intramyocardial pH was measured by a new miniature (0.6 X 3.0 mm) fiberoptic pH transducer. At confirmed rejection, concomitant laparotomy and thoracotomy were performed and pH sensors were implanted in both native (anatomical) and graft hearts. Nine animals at rejection were given methylprednisolone and changes in graft and native heart pH were measured. The pH during absence of rejection, mild acute rejection, and severe acute rejection averaged 7.430 +/- 0.019, 7.233 +/- 0.040 (p less than .02), and 6.860 +/- 0.066 (p less than .02), respectively (mean +/- standard error of the mean). A progressive decline in pH was noted in each heart. In animals receiving steroids, graft heart pH increased over 90 minutes from 6.852 +/- 0.065 to 7.043 +/- 0.077 (p less than .05). Although pH decline may be secondary to either inflammatory or ischemic etiology, histological and ultrastructural analyses demonstrate a predominant inflammatory response with progressive mononuclear cell infiltration, interstitial edema, vascular wall edema, infiltration by polymorphonuclear neutrophil leukocytes, vacuolation of sarcoplasmic reticulum, and disarray of myocytes associated with falling pH. Degree of pH change correlated closely with degree of histological rejection, presence of ECG voltage decline, and change in wall thickness by ultrasound.
Acute Disease↗
Thermal effects of laser and electrical discharge on cardiovascular tissue: implications for coronary artery recanalization and endocardial ablation.
To determine the thermal responses of cardiovascular tissues to laser and electrical ablation, and to characterize the effects of different superfusing media and temperatures on target tissue temperatures and resulting extent of tissue injury, 184 laser and 15 electrical discharges were delivered to segments of human and canine aorta and canine ventricular endocardium. Tissue temperatures were measured 2 mm from the point of contact of laser fiber tip and tissue. When superfusing media consisted of whole blood or plasma at room temperature, a standard 40 J laser discharge caused peak arterial temperatures to rise 29.2 +/- 1.6 degrees C and 30 +/- 1.4 degrees C, respectively; however, tissue cooling was significantly slower in blood than in plasma. When saline solution was superfused, tissue temperatures rose by 11.4 +/- 2.2 degrees C, and tissue cooling occurred significantly faster than with either plasma or blood. The dimensions of the resulting aortic lesions were larger when blood (1.69 +/- 0.26 mm) was superfused than when plasma (1.39 +/- 0.04 mm) or saline (0.77 +/- 0.13 mm) was superfused (p less than 0.0001). Similar findings were observed with ventricular endocardium using blood or saline as the superfusing medium. In arterial tissue, superfusion with cold blood or saline solution resulted in lower peak temperature elevations (22 +/- 3.8 degrees C and 13.5 +/- 1.3 degrees C, respectively) and faster tissue cooling after laser discharge. Corresponding aortic lesion sizes were significantly smaller (1.4 +/- 0.03 and 0.5 +/- 0.02 mm, respectively) than when blood or saline medium was superfused at room temperature (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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Monoclonal antibody to coxsackievirus B4 reacts with myocardium.
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Animals↗
Effect of selenium deficiency on the chronic toxicity of adriamycin in rats.
The effect of selenium deficiency on the chronic toxicity of adriamycin was examined in rats fed diets adequate in vitamin E. Selenium-deficient and selenium-supplemented diets were fed to rats for 10 wk, after which groups of 10 rats fed each diet were given weekly intravenous injections of adriamycin in saline at doses of 0, 0.5 or 1.0 mg/kg body weight for 12 wk. All rats were killed at 24 wk. Even though the cardiac glutathione peroxidase activity in the selenium-deficient group was less than 1% of that of the selenium-supplemented group, the severity of the adriamycin-induced cardiomyopathy was similar in both groups. However, the selenium-deficient rats were more sensitive to the growth-inhibiting effect of the higher dose of adriamycin than the selenium-supplemented rats. Moreover, the lower dose of adriamycin caused a mild nephropathy in 70% of the deficient rats but affected only 10% of the supplemented rats. Selenium status may have to be considered when adriamycin is used as a chemotherapeutic agent.
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