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Biomedical subjects

M E Billingham

Publications and source records attributed to M E Billingham.

At least 109 records · Page 6Linked to original sources
PubMed1990

Experimental osteoarthritis in guinea-pigs.

Cartilage degeneration was induced in the hind knees of guinea-pigs by surgery. Partial medial meniscectomy induced rapidly progressing lesions whereas the lesions induced by section of the lateral collateral ligament with or without section of the medial collateral ligament developed later and progressed more slowly. In all cases the lesions were first seen focally on the medial tibial plateau where they extended both laterally and deeper into the cartilage. Later, lesions appeared on the medial femoral condyle and meniscus, and eventually also on cartilage in the lateral joint compartment. During the later stages, these models had many features of human osteoarthritis. The appearance and progression of spontaneous lesions in the hyaline cartilage of the hind knees of young guinea-pigs first reported by Bendele and Hulman (1988) has been confirmed. Extra ascorbic acid added to the drinking water had a slight chondroprotective effect on the development of spontaneous lesions but gave no significant protection against the development of lesions induced by lateral collateral ligament section.

Animals↗
PubMed1990

Pathology of the transplanted heart and lung.

Combined heart-lung transplantation is now being carried out in many centers around the world. Single-lung and double-lung transplantation are being done in only a few centers and are still considered to be experimental procedures. Combined heart-lung transplantation has been performed successfully in adults and in small children and offers a definite therapeutic alternative to such diseases as severe congenital heart disease with pulmonary hypertension, cystic fibrosis, and primary pulmonary hypertension. At present, the survival statistics for this procedure are similar to those for heart transplantation 15 years ago; it is hoped that, as with heart transplantation, survival rates will improve with better management and more reliable diagnosis of acute rejection, in order to prevent the insidious and relentless onset of obliterative bronchiolitis, which is now the most significant limiting factor to the success of long-term survival in heart-lung transplantation.

Biopsy↗
PubMed1989

Acute myocardial infarction in cardiac transplant recipients.

To characterize the clinical and pathologic features of acute myocardial infarction (AMI) in cardiac transplant recipients, 22 Stanford patients who had 25 documented infarcts at a mean of 3.86 years after transplantation were reviewed. Symptoms included chest pain (2), arm pain (3), weakness (16), dyspnea (11) and palpitations (8). Three episodes were clinically silent, detected only as new electrocardiographic changes during routine follow-up. Of 18 patients hospitalized with symptoms, only 7 had electrocardiographic changes of typical Q-wave AMI; 5 had nonspecific ST-segment changes and 2 had no documented changes. Two had old Q waves. Twelve of the 18 were misdiagnosed at admission as having infection or congestive heart failure. Serial creatine phosphokinase levels were obtained in 13 patients, and values were elevated in 8. Six of 25 AMI episodes were associated with development of congestive heart failure and 4 others led to development of cardiogenic shock. Seven patients died during the acute phase of infarction, 12 were retransplanted from 2 days to 6 months after infarct and 1 died suddenly after discharge. Two healed myocardial infarctions of unknown duration were found at autopsy or on explantation in patients not clinically suspected of having an AMI. All infarcts occurred in patients known to have angiographic evidence of transplant coronary artery disease, based on annual coronary arteriography. At autopsy or explantation all hearts were found to have characteristic diffuse concentric coronary artery narrowing, and 4 (18%) had an unusual pattern of multiple foci of nontransmural AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Frequency of familial nature of dilated cardiomyopathy and usefulness of cardiac transplantation in this subset.

A familial etiology was identified on the basis of family history in 16 (8.75%) of 184 patients undergoing cardiac transplantation at Stanford for endstage dilated cardiomyopathy (DC). These 16 patients, from 11 families, included 5 sibling pairs. To help determine optimal management of such patients, their case histories and posttransplant courses were reviewed. Mean age of patients at presentation was 23 +/- 15 years. In sibling pairs, duration of symptoms from onset to diagnosis was 14 +/- 5 weeks for the first sibling, but only 4 +/- 2 weeks for the second. Progressive cardiac enlargement was documented radiographically in siblings of transplant recipients in 2 families before the onset of symptoms. The posttransplant course with regard to rejection incidence, infectious complications, coronary artery disease and malignancy was similar to that of the 168 patients with nonfamilial DC. Actuarial survival at 5 years after transplantation was 80%. Thirteen patients (including all sibling pairs) are alive 1 to 11 years after transplantation. Sepsis was the cause of death in 3 patients, occurring during the early postoperative period in 2 and following retransplantation for graft atherosclerosis 7 years after the initial transplant in the third patient. Thus, diagnosis of DC in childhood or adolescence mandates evaluation and surveillance of family members, because this disease can progress rapidly. The favorable results of cardiac transplantation for familial DC suggest that it should be promptly considered for such patients with end-stage disease.

Adolescent↗
PubMed1989

Viral infections.

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Heart Transplantation↗
PubMed1989

A hemodynamic and Doppler echocardiographic study of ventricular function in long-term cardiac allograft recipients. Etiology and prognosis of restrictive-constrictive physiology.

Conventional hemodynamic measurements and Doppler echocardiography were used to assess ventricular physiology of the human cardiac allograft and to examine the influence of pertinent clinical factors on chronic myocardial performance. Sixty-four patients (18-55 years old; mean, 39 years) undergoing routine annual hemodynamic assessment were studied. Blood-flow velocity properties across the mitral, tricuspid, and aortic valves were analyzed from Doppler ultrasound recordings. Ten of these patients had elevated diastolic pressures associated with a sharp early diastolic dip followed by an exaggerated and abrupt rise in pressure, consistent with restrictive-constrictive ventricular physiology. Left ventricular dP/dt and stroke volume were lower in these patients compared with the other 54 patients. Doppler echocardiographic indexes of left ventricular filling and ejection in these 10 patients differed significantly. Isovolumic relaxation time and pressure half-time were shorter, peak early mitral and tricuspid flow velocities were higher, and mean aortic flow velocity and acceleration were lower. A higher rejection incidence was the only demonstrable clinical factor associated with impaired ventricular function. Doppler echocardiography may, therefore, noninvasively identify patients with hemodynamic evidence of restrictive-constrictive physiology. This abnormality occurs in approximately 15% of allograft recipients, is associated with impaired systolic performance, and may be related to rejection incidence.

Adolescent↗
PubMed1989

Increasing pericardial effusion in cardiac transplant recipients.

Although pericardial effusion after cardiac surgery is frequent and usually benign, its etiology and prognosis after cardiac transplantation are unknown. During 1 year (1985-1986), 12 of our current transplant population (total, 189) developed moderate or large pericardial effusions confirmed by two-dimensional echocardiography. These effusions occurred within 1 month of transplantation in 10 patients and at 3 months and 4.5 years in the other two. Pericardiocentesis was performed because of clinical evidence of increasing effusions in eight patients, with demonstrable hemodynamic compromise secondary to tamponade in five. Pericardial fluid was sterile in all but one. Endomyocardial biopsy at the time of increasing effusion revealed moderate acute rejection in five patients, mild rejection in three, and no rejection in four. All three patients with mild rejection had moderate acute rejection on subsequent biopsy performed within 7 days. In two of the four with no rejection, repeat biopsy within 5 days showed moderate acute rejection; in a third, moderate rejection was present on biopsy performed 14 days later. Legionella dumoffii was isolated from the pericardial fluid of the fourth patient, whose subsequent biopsies never showed rejection. Three of the 12 patients developed progressive ventricular dysfunction sufficiently severe to require retransplantation. One patient died suddenly 12 months after transplantation, and autopsy examination revealed severe coronary artery disease. Two died of sepsis within 3 months of transplantation. Intense inflammatory infiltrates and thickening of the pericardium and epicardium were characteristically present in explanted and autopsy hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Evaluation of heart-lung transplant recipients with prospective, serial transbronchial biopsies and pulmonary function studies.

The insidious development of obliterative bronchiolitis after heart-lung transplantation is thought to be due to rejection and possibly infection (cytomegalovirus). To evaluate further, we prospectively managed the last 16 consecutive heart-lung transplant recipients with serial transbronchial biopsies with lavage and pulmonary function studies as part of a surveillance protocol or as dictated by clinical presentation. A total of 123 transbronchial biopsies with lavage were performed, 77 for clinical indications (group I) and 46 for routine surveillance (group II). Results of 64 (83.1%) group I biopsies were positive for rejection or infection. Thirty-one of these biopsy specimens showed signs of rejection (29 in group I and two in group II), characterized by a perivascular mononuclear infiltrate, lymphocytic bronchiolitis, and occasionally alveolar septal mononuclear infiltrate. Forty-six serial pulmonary function tests were performed. The forced expiratory volume in 1 second (percent predicted), forced expiratory flow rate between 25% and 75% of the forced vital capacity (percent predicted), and arterial oxygen tension (millimeters of mercury) were significantly reduced from baseline values during rejection episodes: forced expiratory volume in 1 second, 75.7% +/- 20.1% versus 52.7% +/- 18.3% (p less than or equal to 0.05); forced expiratory flow rate between 25% and 75% of the forced vital capacity, 97.6% +/- 30.5% versus 49.8% +/- 22.3% (p less than or equal to 0.05); and arterial oxygen tension, 92.1 +/- 8.8 mm Hg versus 71.4 +/- 18.8 mm Hg (p less than or equal to 0.05). The fall in pulmonary function was reversible with pulse methylprednisolone. Asynchronous heart and lung rejection was documented. Of the 29 episodes of pulmonary rejection, 18 (62%) occurred asynchronously. Ten of the 16 (62%) heart-lung recipients had at least one episode of cardiac rejection. Thirteen of 16 (81%) had at least one episode of lung rejection. Serial transbronchial biopsies with lavage, as dictated by pulmonary function tests and clinical status, have guided early and more specific therapy directed against rejection and infection. With early detection, small airway dysfunction has been reversible.

Adult↗
PubMed1989

Inhibition of accelerated cardiac allograft arteriosclerosis by fish oil.

Accelerated coronary arteriosclerosis remains the most important factor limiting long-term survival of heart transplant recipients, and dietary fish oil supplementation with omega-3 polyunsaturated fatty acids has been suggested to have a protective effect against coronary disease in epidemiologic studies and to inhibit arteriosclerosis in animal experiments. Therefore we tested the hypothesis that fish oil administration inhibits the development of allograft coronary arteriosclerosis by using a heterotopic heart transplant model. Three groups of Lewis rats (n = 10 each) received heterotopic heart transplants from Brown-Norway donors and were treated with cyclosporine intraperitoneally on a tapering schedule. Group 1 received fish oil daily by gavage (2 ml/kg/day; Emulsified Super MaxEpa, Twin Labs, Ronkonkona, N.Y.). Group 2 received an equal amount of safflower oil, as well as aspirin (1 mg/kg/day) and dipyridamole (3 mg/kg/day). Group 3 received safflower oil only. All rats were put to death 110 days later, at which time there was no statistically significant difference in graft function as assessed by palpation (scale 0 to 4, mean = 3.7 +/- 0.5 [+/- standard deviation]; analysis of variance: p = 0.72) or in microscopic grade of rejection (scale, 0 = none to 3 = severe, mean 2.1 +/- 0.6; analysis of variance: p = 0.68) between any of the groups. The coronary arteries were histologically scored for the degree of arteriosclerosis (scale, 0 = normal to 3 = occluded), and a mean grade of coronary disease was calculated for each heart. The fish oil-treated group had significantly less severe allograft coronary arteriosclerosis (analysis of variance: p = 0.005) than did groups 2 and 3 (mean grade 0.23 +/- 0.22 versus 1.04 +/- 0.75 and 0.96 +/- 0.55 (p less than 0.05, Scheffe F test), whereas groups 2 and 3 had similar degrees of coronary disease (p = no significant difference). These data demonstrate that fish oil supplementation inhibited accelerated coronary arteriosclerosis in this cyclosporine-treated heart allograft rat model, whereas antiplatelet agents in these doses were ineffective. Although the mechanism of this protective effect remains incompletely understood, it does not appear to involve enhanced immunosuppression. Fish oil and specific omega-3 polyunsaturated fatty acids should be further investigated as potentially useful agents to ameliorate accelerated allograft coronary arteriosclerosis in other animal species and perhaps eventually in man.

Animals↗
PubMed1988

Airway pathology in the transplanted rat lung.

Bronchiolitis obliterans has emerged as the most significant long-term complication of human heart-lung transplantation. Possible causes include rejection, infection, altered bronchial circulation, and denervation. We attempted to assess the role of some of these possibilities by reviewing the airway histology in nonimmunosuppressed orthotopic rat left lung allografts in three strain combinations: BN-to-LEW (major histocompatibility complex [MHC]-incompatible) n = 27; (LEW X BN)F1-to-LEW, n = 11; and F344-to-LEW (minor loci-incompatible) n = 18. Fifteen syngeneic transplants (LEW-to-LEW) served as controls. After assigning the lungs to a rejection phase (latent, vascular, alveolar, or destructive), the airway pathology was specifically examined. In the latent phase, only changes attributable to transplantation per se were identified. In the vascular phase in the BN-to-LEW rats and (LEW X BN)F1-to-LEW rats, the bronchioles were surrounded by dense cuffs of activated lymphocytes. The lymphocytic infiltrate then progressively involved the lamina propria and epithelium, where it became associated with focal epithelial cell necrosis. Eventually the epithelium became ulcerated (alveolar phase), and the submucosa and luminal surface became replaced by granulation tissue, which frequently protruded into the lumen in a bronchiolitis obliterans pattern. In the destructive phase the changes were similar to those in the alveolar phase, but were more severe. In the F344-to-LEW rats the airway changes were less prominent, although the remainder of the lungs was at comparable phases of rejection. These changes were not observed in the right (nontransplanted) lungs or the control (LEW-to-LEW) lungs. The findings in these animals suggest that the process of rejection affects the airways and may result in posttransplantation bronchiolitis obliterans.

Animals↗
PubMed1988

Ventricular aberrant bands and hypertrophic trabeculations. A clinical pathological correlation.

We reviewed the clinical, hemodynamic, and pathology data of 22 patients with dilated congestive cardiomyopathy and 13 patients with ischemic heart disease who underwent heart transplantation, primarily to improve the pathological definition of left ventricular (LV) and right ventricular (RV) aberrant bands and hypertrophic trabeculations. Overall prevalence of aberrant bands was 37% in th LV and 28% in the RV. Similar values for hypertrophic trabeculations were 43% and 28%, respectively. Compared with ischemic heart disease, our patients with dilated congestive cardiomyopathy had similar ventricular size and wall thickness, but had a higher prevalence of LV aberrant bands (p = .005) and LV hypertrophic trabeculations (p = .01). Aberrant bands were associated, both in the LV and RV, with dilated cavities (p less than .05), whereas hypertrophic trabeculations were associated with more ventricular hypertrophy and smaller LV size. Following morphological and histological analysis of the aberrant bands, we propose their division into two categories: genuine or primary bands (probably congenital in origin) and secondary bands, which most probably represent trabecular structures that develop a free cavitary course following pathological changes in the ventricular wall structure and cavitary geometry. Compared with the muscular RV bands situated mostly in the distal portion of the ventricle, LV bands were usually fibrotic and had at least one point of insertion in the inflow or outflow tract. The pattern of trabecular hypertrophy was also different in the two ventricles. Ventricular arrhythmias and thrombi occurred equally in patients with and without bands or trabeculations.

Adolescent↗
PubMed1988

The postsurgical heart. The pathology of cardiac transplantation.

Cardiac transplantation offers an excellent chance of long-term survival and functional rehabilitation for the carefully selected patient with end-stage heart disease. The role played by the pathologist in the management of cardiac transplant recipients is a very important one. Although much work is being carried out currently on noninvasive procedures to predict acute rejection, at this time the morphological index of rejection by endomyocardial biopsy is still the only reliable one. Noninvasive techniques are more sensitive because the whole heart can be studied; however, they are still much less specific and cannot distinguish infection from rejection or ischemia. The current management and survival of cardiac allografts depends as much on the pathologist as on his clinical colleagues.

Adolescent↗
PubMed1988

Ultrastructural morphometric analysis of endomyocardial biopsies. Idiopathic dilated cardiomyopathy, anthracycline cardiotoxicity, and normal myocardium.

Anthracycline cardiotoxicity has been regarded as a model of idiopathic dilated cardiomyopathy, and similar histopathologic changes have been described in both. Our purpose was to quantify these changes, using computer-assisted ultrastructural morphometry, and compare them with normal myocardium. Right ventricular endomyocardial biopsies were taken from 10 patients with anthracycline cardiotoxicity (AC), 10 patients with idiopathic dilated cardiomyopathy (CM), and 10 disease-free transplant donor heart controls (C). Mean myocyte width (corrected for sarcomere length) was significantly greater in CM (29.3 microns +/- 7.2) than in AC (19.2 +/- 3.2) or C (20.3 +/- 3.4). Mean nuclear area was significantly greater in CM (88.7 microns 2 +/- 27.1) than in AC (54.2 +/- 15.3) or C (45.0 +/- 9.2). Nuclear form factor (corrected for sarcomere length) was significantly lower (indicating a more irregular outline) in CM (0.28 +/- 0.09) than in AC (0.46 +/- 0.06) or C (0.36 +/- 0.04). Mean mitochondrial area was significantly smaller in CM (0.30 microns 2 +/- 0.05) than in C (0.35 +/- 0.05), but differences between AC (0.35 +/- 0.09) and the other groups were not significant. These results suggest that anthracycline cardiotoxicity is not, quantitatively, a faithful model of idiopathic dilated cardiomyopathy.

Adolescent↗