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Biomedical subjects

M E Billingham

Publications and source records attributed to M E Billingham.

At least 181 records · Page 10Linked to original sources
PubMed1984

Post-transplant obliterative bronchiolitis and other late lung sequelae in human heart-lung transplantation.

Since March 1981, 19 patients have undergone heart-lung transplantation for end-stage pulmonary vascular disease, with 14 long-term survivors. In five of the survivors, obstructive airway disease has developed with the superimposition of a progressive restrictive ventilatory defect in three of them. None of these five patients showed a tendency for spontaneous improvement of flow rates. Biopsy and postmortem material was available in four of the five patients and showed obliterative bronchiolitis (OB) in three. A fourth patient showed clinical and physiologic data consistent with obliterative bronchitis, but histologic material was not available. Obstructive lung disease without restrictive features developed in a fifth patient, but no histologic evidence of OB was found at transbronchial biopsy. In addition to OB, recurrent lung infections were found in all patients, significant pleural fibrosis in two patients, and bronchiectasis in one patient. Despite these long-term sequelae of human heart-lung transplantation, ten of the 14 surviving patients are leading relatively normal lives.

Adult↗
PubMed1984

Early response of cartilage to abnormal factors as seen in the meniscus of the dog knee after cruciate ligament section.

Ultrastructural changes in the medial meniscus of the knee were studied following section of the anterior cruciate ligament in 7 dogs. As compared with the contralateral control knee, collagen fibrils became abnormally widely spaced and disoriented from 1 month after operation and amorphous material on the (femoral) articular surface increased in thickness. In superficial cells, granular endoplasmic reticulum and Golgi membranes were more profuse and lipid droplets increased in number from 1 week. Both superficial and deeper cells were very active at 1 and 2 months after operation and the nuclear fibrous lamina had increased in thickness. Some cell degeneration occurred in the superficial zone from 1 month. At 15 months both matrix and cells appeared to have returned to normal. These changes are compared with those in articular cartilage after cruciate ligament section and with the effects of intravenous papain on cartilage.

Animals↗
PubMed1984

Heart transplant rejection monitored by signal-averaged electrocardiography in patients receiving cyclosporine.

Data from standard and high-frequency signal-averaged electrocardiograms (ECGs) were correlated with the results of 67 endomyocardial biopsies performed in 20 cyclosporine-treated heart transplant recipients. Eight patients (group 1) were in the early postoperative hospitalization period and 12 patients (group 2) were studied after their hospital discharge. The biopsy samples were classified as normal or as indicating early (cellular infiltrate) or definite rejection (myocyte necrosis). The standard ECG parameter studied was the summated QRS voltage in leads I, II, III, V1, and V6. The signal-averaged ECG was evaluated for QRS duration, high-frequency voltage amplitude of the total QRS complex and of its three thirds, peak QRS voltage amplitude, and QRS integrated voltage-time product. The ECG recording obtained at the time of a first normal biopsy sample was considered the normal reference to which additional tracings from the same patient were compared. At the time of subsequent biopsies, the standard ECG parameter showed poor reproducibility (r = .58) and it was inadequate in defining rejection episodes in the early or late postoperative period. The signal-averaged ECG was more reproducible (r = .83) and more accurate in detecting definite rejection during the late posttransplant period than the standard ECG. In group 2 patients, 92% of abnormal signal-averaged ECG recordings were associated with rejection episodes and only 13% of normal tracings were associated with definite rejection. The method was inadequate, however, in monitoring patients during the early postoperative period and in detecting mild forms of rejection in the late postoperative phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

The glycosaminoglycans in menisci in experimental and natural osteoarthritis.

The glycosaminoglycans in the menisci of beagles 5--7 years old were analyzed at various times after osteoarthritis was induced by sectioning the anterior cruciate ligament of one knee; the unoperated knee served as control. In the first month after induction, there were signs of inflammation in the operated joint. After 1 week, the water content was elevated and the glycosaminoglycan content (per dry weight) was reduced. The content of keratan sulfate decreased more than that of chondroitin sulfate, but the hyaluronic acid content did not change consistently. The relative proportions of chondroitin-4-sulfate, chondroitin-6-sulfate, and dermatan sulfate remained unchanged. After 3--18 months, the glycosaminoglycan levels reverted to normal, and there was some evidence that after 15--18 months, they were elevated above normal. These results, together with results obtained from single examples of mild and severe osteoarthritis in working foxhounds, suggest that, in contrast to articular cartilage, the meniscus is capable of some regeneration in response to injury.

Animals↗
PubMed1983

Sensitivity and specificity of radionuclide ejection fractions in doxorubicin cardiotoxicity.

We examined radionuclide-determined left ventricular ejection fractions (LVEF) at rest and during graded exercise in 37 patients receiving doxorubicin (Adriamycin) therapy in whom the risk of developing congestive heart failure (CHF) was precisely defined by endomyocardial biopsy and right heart catheterization. Echocardiographic (Echo %FS) and phonocardiographic (PEP/LVET) measurements of LV function were also determined. An abnormal LVEF at rest (less than or equal to 45%) had a sensitivity of 53% and a specificity of 75% for detecting patients at moderate or high risk of developing CHF. The addition of exercise LVEF increased the sensitivity of detection of moderate or high-risk patients to 89% but lowered the specificity to 41%. Exercise LVEF improved the sensitivity of detection of high-risk patients from 58% to 100%. Echo %FS and PEP/LVET yielded lower sensitivities than rest or exercise LVEF. As a single test, exercise LVEF possesses the sensitivity for use as a screening method for anthracycline cardiotoxicity, but the lack of specificity prevents the use of single values as a definitive test. Single rest LVEF determinations, although more specific than exercise LVEF, do not possess the sensitivity for use as screening or definitive tests.

Adult↗
PubMed1983

Study of the normal and failing isolated human heart: decreased response of failing heart to isoproterenol.

We evaluated the effects of isoproterenol in right ventricular papillary muscles derived from normal and failing isolated human hearts. Basal values for the peak force developed, rate of force development (dF/dt), and time to peak tension (TPT) were similar in both groups. Isoproterenol produced a significantly smaller (p less than 0.05) increase in peak force developed and dF/dt in failing papillary muscles. The half equivalent dose (ED50) of isoproterenol was fivefold higher in failing muscle as compared to normal muscle. We conclude that failing cardiac muscle demonstrates decreased responsiveness to beta-receptor mediated stimulation.

Adolescent↗
PubMed1983

Reduced cardiotoxicity of doxorubicin delivered on a weekly schedule. Assessment by endomyocardial biopsy.

Endomyocardial biopsy was done 119 times in 98 patients receiving doxorubicin therapy once every 3 weeks and 41 times in 27 patients receiving doxorubicin therapy weekly. Factors contributing to the degree of anthracycline-induced endomyocardial injury were evaluated. Neither age, sex, type of malignancy, concomitant use of other chemotherapeutic agents including cyclophosphamide, nor history of cardiac disease or hypertension influenced the extent of the endomyocardial injury. The dose of doxorubicin (p = 0.0001) and the schedule (weekly versus 3 weekly) (p = 0.0020) independently predicted the degree of endomyocardial damage in multivariate analyses. Previous cardiac irradiation had borderline significance (p = 0.074) in predicting endomyocardial damage in this analysis. Doxorubicin therapy administered on a weekly schedule is associated with less anthracycline-induced cardiac damage than is doxorubicin therapy delivered in the conventional, 3-weekly schedule.

Adult↗
PubMed1983

Diagnosis and treatment of allograft rejection in heart-lung transplant recipients.

Six patients received heart-lung transplants between March, 1981, and January, 1982. There were four women and two men between 26 and 45 years of age, three with primary pulmonary hypertension and three with congenital heart disease and pulmonary hypertension (Eisenmenger's syndrome). Immunosuppression was primarily with cyclosporin-A, with additional corticosteroid, azathioprine, and rabbit antihuman thymocyte globulin. Six episodes of allograft rejection in four patients (10, 11, 21, 24, 53, and 86 days after transplantation) were detected by means of transvenous endomyocardial biopsy. All patients experienced pulmonary edema early after transplantation (reimplantation response), and two patients required mechanical ventilatory support for allograft rejection at 10 and 11 days. Treatment of rejection consisted of intravenous methylprednisolone (four episodes) or augmented oral prednisone (two episodes), with resolution. No episode thought to be pulmonary rejection has occurred in the absence of cardiac findings. Four patients are alive from 6 to 15 months after transplantation and are functionally normal. Early experience with heart-lung transplantation suggests (1) that allograft rejection can be detected by cardiac findings and successfully treated by augmented corticosteroids, (2) that lung rejection does not occur in the absence of cardiac findings, (3) that the frequency and severity of rejection episodes are not greater than with standard cardiac transplantation, and (4) that the frequency of rejection episodes is highest within the first 60 days after transplantation.

Adult↗
PubMed1983

Ultrastructural changes in articular cartilage after experimental section of the anterior cruciate ligament of the dog knee.

Ultrastructural changes in articular cartilage were studied in joint laxity induced by severing the anterior cruciate ligament of the right knee in sixteen mature dogs. The left knees provided controls; sham operations on six other dogs consisted of stab incision only, leaving the ligament intact. Cartilage from the medial tibial condyles was examined at intervals from two days to eighteen months later. In the superficial zone of the cartilage, collagen fibrils became abnormally widely spaced at four days, and narrower fibrils appeared from seven days after operation. Chondrocytes, particularly in the middle zone, became more active, with hypertrophy of cytoplasmic organelles detectable from four days. Superficial cells were initially healthy and became more numerous while their lipid content increased. The articular surface was fissured from two months and cell degeneration was rarely seen until several months after operation. These findings correlate with previous biochemical studies and are similar to early changes noted in degeneration of human articular cartilage.

Animals↗
PubMed1983

Calcium antagonists suppress atherogenesis in aorta but not in the intramural coronary arteries of cholesterol-fed rabbits.

We tested the effects of the calcium antagonists lanthanum, diltiazem, and flunarizine on the development of atherosclerosis in rabbits fed a 2% cholesterol diet. The drugs were given orally and were well tolerated. In the cholesterol control animals, 52.2% of the thoracic aortic intimal surface was Sudan IV positive. This was reduced by 37% (p less than 0.05) with lanthanum, 37% (p less than 0.05) with diltiazem, and 34% (p less than or equal to 0.06) with flunarizine. In all cholesterol-fed animals, the intramural, but not subepicardial, coronary arteries were severely diseased. The extent and distribution of this disease were not altered by the various drug interventions. Thus, the calcium antagonists lanthanum, diltiazem, and flunarizine suppress atherogenesis of the rabbit aorta but have no effect on the extent or distribution of atherosclerosis in the intramural coronary arteries.

Animals↗
PubMed1982

Decreased catecholamine sensitivity and beta-adrenergic-receptor density in failing human hearts.

To identify the role of the myocardial beta-adrenergic pathway in congestive heart failure, we examined beta-adrenergic-receptor density, adenylate cyclase and creatine kinase activities, muscle contraction in vitro, and myocardial contractile protein levels in the left ventricles of failing and normally functioning hearts from cardiac-transplant recipients or prospective donors. Eleven failing left ventricles had a 50 to 56 per cent reduction in beta-receptor density, a 45 per cent reduction in maximal isoproterenol-mediated adenylate cyclase stimulation, and a 54 to 73 per cent reduction in maximal isoproterenol-stimulated muscle contraction, as compared with six normally functioning ventricles (P less than 0.05 for each comparison). In contrast, cytoplasmic creatine kinase activity, adenylate cyclase activities stimulated by fluoride ion and by histamine, histamine-stimulated muscle contraction, and levels of contractile protein were not different in the two groups (P less than 0.05). We conclude that in failing human hearts a decrease in beta-receptor density leads to subsensitivity of the beta-adrenergic pathway and decreased beta-agonist-stimulated muscle contraction. Regulation of beta-adrenergic receptors may be an important variable in cardiac failure.

Adenylyl Cyclases↗
PubMed1982

Efficacy and cost of cardiac monitoring in patients receiving doxorubicin.

We compared the incidence of heart failure (CHF), CHF mortality and CHF severity in cancer patients (pts) treated with doxorubicin (DXR) in the presence and absence of cardiologic monitoring (CM). CM consisted of endomyocardial biopsy and right heart catheterization as definitive tests with and without echocardiograms and phonocardiographically derived systolic time intervals as screening tests. CHF incidence was very low (0.03) in non-CM pts without risk factors (RF). RF pts had a CHF incidence of 0.17 without and 0.06 with CM (P = 0.107). Five of 58 RF pts in the non-CM group and 0 of 49 RF pts in the CM group died of problems related to CHF. CHF symptomatology by NYHA criteria was less in CM RF pts than non-CM RF pts (P = 0.034). The prevention of CHF mortality and morbidity in CM pts was not due to administering less DXR, as CM pts actually received an average of 43 mg/m2 more DXR than non-CM pts. We conclude that pts without RF need no CM during treatment with DXR, and that CM can reduce CHF severity and CHF mortality in RF pts.

Adult↗
PubMed1982

Heart-lung transplantation: successful therapy for patients with pulmonary vascular disease.

We report our initial experience with three patients who received heart-lung transplants. The primary immunosuppressive agent used was cyclosporin A, although conventional drugs were also administered. In the first patient, a 45-year-old woman with primary pulmonary hypertension, acute rejection of the transplant was diagnosed 10 and 25 days after surgery but was treated successfully; this patient still had normal exercise tolerance 10 months late. The second patient, a 30-year-old man, underwent transplantation for Eisenmenger's syndrome due to atrial and ventricular septal defects. His graft was not rejected, and his condition was markedly improved eight months after surgery. The third patient, a 29-year-old woman with transposition of the great vessels and associated defects, died four days postoperatively of renal, hepatic, and pulmonary complications. We attribute our success to experience with heart-lung transplantation in primates, to the use of cyclosporin A, and to the anatomic and physiologic advantages of combined heart-lung replacement. We hope that such transplants may ultimately provide an improved outlook for selected terminally ill patients with pulmonary vascular disease and certain other intractable cardiopulmonary disorders.

Adult↗
PubMed1982

The use of 111In-labeled lymphocyte imaging to evaluate graft rejection following cardiac transplantation in dogs.

Lymphocytes separated from venous blood from six dogs who had heterotopic cardiac transplants have been labeled using 111In-oxine. Labeled lymphocytes were reinjected into the dogs and imaging of the heart carried out over the successive 3 or 4 days. For comparison serial ECGs and punch biopsies of the heart were obtained. Abnormal uptake of labeled lymphocytes in the donor heart was clearly visible in three of the six dogs, faintly visible in two and not seen in one. 630 mu Ci 111In was used in the dog where no uptake was seen and subsequent studies showed this amount of the radiopharmaceutical was toxic to lymphocytes. In the remaining five dogs the mean ratio of uptake of 111I in donor to recipient heart was 14:1 (range 6.5:1--21:1). The lack of substantial uptake in the transplanted heart of two dogs in attributed to a delay in rejection relative to the time the labeled lymphocytes were injected. The results suggest that 111In-labeled lymphocytes have potential as a noninvasive test for detecting rejection of cardiac transplants.

Animals↗