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Biomedical subjects

M E Billingham

Publications and source records attributed to M E Billingham.

At least 163 records · Page 9Linked to original sources
PubMed1985

Pharmacotoxic myocardial disease: an endomyocardial study.

Drug-induced toxic changes in the myocardium have become an increasing problem. The effect of drugs on heart morphology may be acute or cumulative. In general, adverse drug reactions manifest themselves as myocarditis (toxic or hypersensitivity), cardiomyopathy with chamber dilatation, or restrictive disease. Drugs affecting embryologic development of the heart will not be discussed. Drugs causing myocarditis can be divided into: toxic myocarditis, e.g., cyclophosphamide. The morphologic changes are dose-related and have lesions of different ages, which include myocyte necrosis with hemorrhage and vasculitis. Fibrous endocarditis, e.g., methysergide. These reactions include thickening of the endocardium and sometimes the cardiac valves with fibrosis. Drugs causing hypersensitivity myocarditis, e.g., thiazide diuretics. In this case, the lesions are not dose-related, are the same age, and there is an eosinophilic infiltrate. Drugs causing cardiomyopathic-like changes of ventricular dilatation and failure, e.g., anthracyclines, particularly adriamycin. This group of drugs cause a gradual myofibrillar loss within cardiac myocytes and a sarcotubular dilatation which is characteristic. The damaged cells are replaced by fibrosis and ventricular failure ensues. With the rapid synthesis of new drugs, the problem of drug cardiotoxicity may be an ever-increasing problem. With the more widespread use of the endomyocardial biopsy, drug-induced heart disease can be documented and the effects of different methods of drug delivery and pharmacologic antagonists studied.

Antibiotics, Antineoplastic↗
PubMed1985

Pathologic pulmonary alterations in long-term human heart-lung transplantation.

Twenty-one patients with end-stage pulmonary hypertension underwent combined allograft heart-lung transplantation after 1980. Almost 80 per cent of these patients survived beyond the immediate postoperative period, with the longest survival period more than 3 1/2 years at the time of this report. Five patients died in the perioperative or immediate postoperative period, and 11 returned to normal lives with essentially normal pulmonary function. In the remaining five allograft recipients recurrent respiratory infections and progressive obstructive airway disease developed, with superimposed restrictive deficits in three of them. Two open lung biopsies, two autopsies, and one retransplantation were performed in these recipients. Morphologically, these allograft recipients showed extensive bronchiolitis obliterans, interstitial and pleural fibrosis, and accelerated arterial and venous arteriosclerosis. Bronchiolitis obliterans may prove to be a significant complication of heart-lung transplantation.

Adult↗
PubMed1985

Echocardiographic recognition of paraseptal structures.

Improved echocardiographic equipment provides detailed images of the heart and shows anatomic paraseptal structures previously not well defined. Echocardiograms were analyzed from 33 patients who later underwent cardiac transplantation, and the paraseptal structures noted were correlated with the pathologic specimens. Patterns associated with right ventricular chordae tendineae, the moderator band and the posterior papillary muscle are illustrated. Hypertrophic and fibrotic right ventricular trabeculae and left ventricular paraseptal bands are noted. These structures can be specifically sought and identified using the current generation of echocardiographs, thereby avoiding potential problems of septal definition and measurement.

Adolescent↗
PubMed1985

Long-term cardiac and pulmonary histology in primates following combined heart and lung transplantation.

To investigate the long-term histologic consequences of combined heart and lung transplantation, heart and lung biopsies were obtained from six rhesus monkeys; two had undergone heart-lung autotransplantation 3.5 and 4.5 years previously, two were the recipients of heart-lung allografts 4.1 and 4.5 years previously, and the results were compared with two normal control animals. Cyclosporine had been used as maintenance immunosuppression in the allograft group. The heart and lung biopsies in the autograft animals were essentially normal. Dense adhesions were noted in the allografts, adn in one the visceral pleura was grossly thickened. Cardiac biopsies in the allografts were unimpressive, with a normal myocardium in one, and minimal interstitial fibrosis in the other. Intimal hyperplasia was present in the pulmonary arterioles of one of the allografted animals. Focal scarring was present in the lung of one allograft recipient, and the other animal showed severe thickening and fibrosis of the alveolar septae, as well as marked interstitial fibrosis such that large areas of the specimen were replaced by connective tissue. Histologic abnormalities in the allografted lungs correlated with the abnormal hemodynamics in these animals reported in a previous study. It is suggested that the histologic appearances in the lung are a consequence of chronic rejection, and that these findings may become a significant problem in human heart-lung transplant recipients.

Animals↗
PubMed1985

Long-term results, hemodynamics, and complications after combined heart and lung transplantation.

During the first 31/2 years of the Stanford heart-lung transplant program, 23 transplants have been carried out in 22 patients with severe pulmonary vascular disease. Actuarial survival curves predict 1 and 2 year survival rates of 71% and 57%, respectively, for all patients. As a result of increasing experience, the early mortality of 26% has been reduced, with only one early death occurring in the last eight patients; prior cardiac surgery was a contributing factor in three of the six patients suffering early deaths. Two late deaths occurred in the series 14 and 15 months after operation. One patient died suddenly as a result of an acute myocardial infarct and the other patient died because of respiratory failure. At autopsy, both patients had severe proliferative coronary atherosclerosis with obliterative bronchiolitis affecting the lungs. An additional patient required a retransplant for obliterative bronchiolitis 37 months after the initial procedure, and he too was found to have severe coronary artery disease. Hemodynamics and left ventricular function were normal in patients studied 1 and 2 years after undergoing the transplantation procedure. Thus, the early mortality and morbidity of combined heart and lung transplantation has been significantly reduced, but the long-term complications, particularly graft atherosclerosis and obliterative bronchiolitis, are yet to be fully controlled.

Actuarial Analysis↗
PubMed1985

Ultrasonic tissue characterization: detection of acute myocardial ischemia in dogs.

Ultrasonic tissue characterization is a new area of investigation in the field of cardiac ultrasound. The amplitude and frequency of the ultrasound signal are normally altered as the signal penetrates through tissue. It is assumed that the amplitude distribution and frequency shift of diseased or edematous tissue are different than those of normal tissue. A statistical approach to the analysis of the unprocessed radiofrequency signal in the amplitude domain was used to study the effect of acute myocardial ischemia on the parameter mean amplitude/standard deviation of the amplitude (MSR). Ten dogs were anesthetized and underwent left lateral thoracotomy. Baseline mean MSR from the interventricular septum was 1.99 +/- 0.05, but increased by 30 min after coronary artery occlusion and started to plateau at 1 hr (mean 2.24 +/- 0.06). Reproducibility in noninfarcted myocardium (left ventricular inferoposterior wall) was good, with a mean MSR of 2.00 +/- 0.05 at baseline and 1.98 +/- 0.04 3 to 4 hr later. There was no difference in mean MSR when data were obtained through chest wall and when they were obtained directly from the surface of the heart. We conclude that statistical analysis in the amplitude domain of the unprocessed radiofrequency signal can detect acute myocardial ischemia within 30 min after coronary artery occlusion, provides reproducible measurements, and is unaffected by chest wall filtering.

Animals↗
PubMed1985

Mildly dilated congestive cardiomyopathy.

Five patients with only mildly dilated ventricles but other features typical of congestive cardiomyopathy underwent cardiac transplantation for class IV NYHA heart failure. The findings of clinical studies, cardiac catheterization, endomyocardial biopsy, and pathologic examination of the removed hearts in this group with mildly dilated congestive cardiomyopathy (MDCM) were compared with similar data in four patients with idiopathic restrictive cardiomyopathy (IRCM) and in 10 patients with typical dilated congestive cardiomyopathy (DCM). In comparison with the other groups, patients with MDCM had a higher incidence of familial cardiomyopathy (p = .02) and a shorter symptomatic period than patients with IRCM (p less than .02). Patients with both MDCM and DCM had globular hearts (with predominant left ventricular dilatation), congestive hemodynamics and poor left ventricular contractility (ejection fraction 12% to 19%), and high incidence of ventricular thrombi. Patients with IRCM showed normal ventricular size, marked atrial dilatation, restrictive hemodynamics, mild-to-moderate decrease in left ventricular contractility (ejection fraction 29% to 55%), and absence of ventricular thrombi. Cardiac index, ventricular wall thickness, and light microscopic findings were similar in the three groups of patients. Electron microscopy showed no myofibrillar loss in patients with IRCM but mild (partial) or moderate-to-severe (almost total) myofibrillar loss in those with MDCM and DCM, respectively. We conclude that end-stage congestive cardiomyopathy may occur without significant ventricular dilatation and patients with MDCM have heart sizes intermediate between those found in IRCM and DCM but their clinical, hemodynamic, and pathologic findings are virtually identical to those of patients with typical DCM.

Adult↗
PubMed1985

Bronchoscopy after cardiopulmonary transplantation.

Eighteen combined heart and lung transplant operations were performed between March, 1981, and March, 1984. Six of these patients have undergone bronchoscopy, at varying intervals after transplantation. Five of these procedures were done for specific clinical indications; one was done incidentally, during another surgical procedure requiring general anesthesia. All patients had intact, healing tracheal anastomotic suture lines; there were no instances of tracheal stenosis. The distal tracheobronchial tree appeared endoscopically normal in the transplanted lungs, except in areas of known infiltrates. Four of the patients had endobronchial biopsies, and alveolar eosinophilic proteinaceous exudate and submucosal mononuclear infiltrate were consistent features. Two of the later biopsies suggest that squamous metaplasia of the respiratory epithelium may occur with long-term follow-up. Controversy exists as to the optimal technique for tracheal anastomosis, but in the case of the steroid-treated, immunosuppressed transplant patient, continuous anastomosis with polypropylene has yielded satisfactory results.

Bronchi↗
PubMed1985

Cyclosporine induced myocardial fibrosis: a unique controlled case report.

Many patients treated with cyclosporine in the Stanford Heart Transplant Program have exhibited perimyocytic fibrosis in the donor heart, seen on endomyocardial biopsy specimen. Although restrictive hemodynamic effects have not been observed up to three years after transplantation, there is a possibility that such changes could become a problem. With the increasing use of cyclosporine in non-cardiac organ transplantation, it is of interest to examine the effect of this drug upon the non transplanted heart. This was possible in a man who underwent a heterotopic heart transplantation 3 1/2 years ago, and who has been followed with serial endomyocardial biopsies from both hearts. Although there were no episodes of rejection the donor heart developed significant perimyocytic fibrosis which was not seen in the native heart. This study suggests that cyclosporine induced fibrosis only occurs in the transplanted heart.

Adult↗
PubMed1985

The lymphocyte subpopulations in cyclosporine-treated human heart rejection.

Monoclonal antibodies are being used as specific therapeutic agents for treating organ rejection. This type of treatment requires that the pattern and type of infiltrating cells in the graft during acute rejection be defined. In this study 24 endomyocardial biopsies from cyclosporine-treated human heart allograft recipients were obtained during acute rejection. The biopsies were stained with immunological markers to define the infiltrating cells. The biopsies were divided into three groups; mild, moderate and resolving acute rejection. In all groups T-lymphocytes (marked with the monoclonal Leu-4) were the predominant cells with absence of B-lymphocytes (marked with T015). The results of this study showed that cyclosporine-treated heart transplant recipients have a mixed suppressor/cytotoxic (Leu-2a) and helper/inducer (Leu-3) myocardial infiltrate in contrast to the biopsies of recipients treated with azathioprine, in which suppressor/cytotoxic T-lymphocytes (Leu-2a) were predominant. A clear sequential pattern of changes in the T-cell subpopulations did not emerge, although macrophages became more prevalent with resolving rejection.

Acute Disease↗
PubMed1984

Calcification of aortic versus mitral porcine bioprosthetic heart valves: a radiographic study comparing amounts of calcific deposits in valves explanted from the same patient.

Calcium detected by radiography was compared in 10 pairs of aortic and mitral glutaraldehyde-treated porcine bioprosthetic heart valves explanted from 10 patients (7 men and 3 women), aged 19 to 68 years (mean 43). Both valves of 6 pairs of valves had undergone primary tissue failure (revealed by cardiac catheterization and angiography) and 1 valve of the other 4 pairs of valves had undergone primary tissue failure. These porcine valves had been implanted from 2 1/4 to 9 years (mean 5 3/4). All 20 explanted valves contained calcium. The grade of calcium was the same in 4 pairs of valves (grade 2+ or 3+), and 1 grade different in 4 pairs of valves (grade 1+ to 4+), with the greater calcium evenly divided between the 2 valve positions. There was more than 1 grade greater mitral valve calcium in 2 pairs of valves (grade 3+ and 4+ mitral vs 1+ and 2+ aortic, respectively). Thus, calcium is usually present in both aortic and mitral valve positions when bioprosthetic valves of this type in either valve position fail as a result of primary tissue failure, and radiographic calcium in porcine bioprosthetic valves is usually similar in grade in both the aortic and mitral valve positions.

Adult↗
PubMed1984

In vivo and in vitro stimulation of chondrocyte biosynthetic activity in early experimental osteoarthritis.

The biosynthesis of proteoglycans in the menisci and articular cartilages of the knee (stifle) of mature beagles was studied in the early stages of experimental osteoarthritis. The rate of proteoglycan synthesis, determined by systemic labeling in vivo at 21, 42, and 84 days after sectioning of the anterior cruciate ligament, was generally found to be 1.5-2.5-fold higher than control in articular cartilages and 3-10-fold higher than control in menisci. The medial meniscus was more stimulated than the lateral meniscus, and the medial tibial plateau under the meniscus was more stimulated than the adjacent tibial area. This area-specific stimulation suggests the involvement of mechanical factors in the cellular response. The rate of proteoglycan synthesis determined in vitro at 7, 14, and 21 days after operation was also about 2-fold higher than control in articular cartilages and about 3-fold higher in menisci. This increase in biosynthetic activity in vitro was confirmed by 35S-autoradiography and appeared to be due to general stimulation of existing chondrocytes, particularly in the middle and deep zones of the articular cartilage and throughout the meniscal cartilage. The rate of proteoglycan synthesis determined in vitro in cartilages from 2-week and 3-week sham operated joints was also increased relative to controls, suggesting that humoral as well as mechanical factors are involved in stimulating chondrocyte activity.

Animals↗
PubMed1984

Demonstration of increased proteoglycan turnover in cartilage explants from dogs with experimental osteoarthritis.

The turnover of proteoglycans (assessed by the release into the medium of newly synthesised [35S]-proteoglycan) in explant cultures of articular cartilage from various anatomical sites of the knee joints (stifle) of mature beagles with experimental osteoarthritis has been studied with the following findings: (a) The proportion of newly synthesised proteoglycans released from cartilage explants maintained in vitro was generally increased for cartilage from operated compared with nonoperated control joints. (b) At 3 weeks after surgery there was a significant increase in the release of [35S]-proteoglycans from explants of the lateral and medial tibial plateaux of operated joints compared with sham-operated joints but not from other sites. On the other hand, when this comparison was made at 3 to 6 months after surgery, significant increases in the release of [35S]-proteoglycans were observed from cartilage of all anatomical areas except the patellar groove. (c) The release of [35S]-proteoglycan from cartilage explant cultures was dependent on live chondrocytes, since freeze-thawing the tissue immediately after labelling markedly reduced the release from both normal and osteoarthritic cartilage.

Animals↗
PubMed1984

Morphologic effects of defibrillation: a preliminary report.

A 72-yr-old man receiving more than 300 separate DC countershocks in 2 wk exhibited morphologic heart changes, including areas of coagulation necrosis in the subepicardium and areas of frank hemorrhage. In other sites the myocytes were pathologically contracted, a finding previously demonstrated in experimental animals as a result of defibrillation but not seen in man. We suggest that these changes may occur more often than has been previously supposed and thus may be of clinical importance.

Aged↗
PubMed1984

Quantitative pharmacologic responses of normal and atherosclerotic isolated human epicardial coronary arteries.

We studied quantitative aspects of coronary artery contraction in isolated epicardial coronary ring segments from 49 human hearts. The order of maximal tension developed by drugs in normal calcium (ionized calcium, 1.26 mM) solution was U-44069 (a prostaglandin endoperoxide analog) greater than histamine greater than carbachol greater than serotonin greater than phenylephrine greater than ergonovine. In Ca2+-free solution these same drugs mediated a lesser degree of contraction, which demonstrates that the human coronary artery uses both "intracellular" and "extracellular" calcium in hormone receptor-activated contraction. U-44069, histamine, carbachol, and phenylephrine produced calcium-free/normal calcium maximal responses of 62.9% 48.7%, 39.8%, and 37.2%, respectively. Morphologic characteristics of the atherosclerotic plaques within the vessel lumen and the degree of myocardial dysfunction did not qualitatively alter these contractile responses. However, severely atherosclerotic coronary segments were supersensitive to histamine, but not to carbachol or calcium. In conclusion, the human epicardial coronary artery is a highly reactive vessel that uses at least two calcium pools to couple contraction. Receptor-coupled agonists differ in their abilities to mediate contraction and in the degree to which each calcium pool is used, and the presence of atherosclerosis potentiates the contractile response to histamine.

Calcium↗
PubMed1984

Echocardiographic recognition and implications of ventricular hypertrophic trabeculations and aberrant bands.

The accuracy of two-dimensional echocardiography in the recognition of aberrant ventricular bands and pathologic trabeculations (hypertrophic, fibrotic, or both) was assessed in 35 patients who underwent cardiac transplantation and pathologic examination. At pathologic study the prevalence of specific intracavitary structures ranged from 28% to 43%. Left ventricular thrombi were found in 12 patients (34%) and right ventricular thrombi in three (9%). Echocardiography accurately defined left ventricular aberrant bands and left ventricular thickened or fibrotic trabeculations. Bands, trabeculations, and thrombi each showed characteristic echocardiographic patterns. In the right ventricle, these structures were recognized, but accurate discrimination among them was not possible by echocardiography. Aberrant bands and pathologic trabeculations mimicked or obscured fresh or organized thrombi in three patients on two-dimensional echocardiography. Left ventricular longitudinal bands and pathologic right ventricular trabeculations obscured the interventricular septal border in four patients; the presence of these abnormalities could lead to the erroneous diagnosis of asymmetric septal hypertrophy on M mode echocardiography. By expressing the accuracy of two-dimensional echocardiography in the recognition of left ventricular anomalous bands, our results support the feasibility of prospective studies to clarify their clinical significance.

Adolescent↗