Structure of newly synthesised (35S)-proteoglycans and (35S)-proteoglycan turnover products of cartilage explant cultures from dogs with experimental osteoarthritis.

The structure of newly synthesised proteoglycans from explant cultures of cartilage from joints subjected to transection of the anterior cruciate ligament (osteoarthritic) and from normal (non- or sham-operated) joints was examined. The structure of the products of proteoglycan turnover was also examined using explants of normal and osteoarthritic cartilage maintained in culture for a 48 h chase period. The findings were as follows: Newly synthesised (35S)-proteoglycans extracted from cartilage explants from osteoarthritic joints whether examined 3 weeks, 3 months, or 6 months after surgery were larger than those from corresponding normal cartilage.

Endomyocardial biopsy detection of acute rejection in cardiac allograft recipients.

Endomyocardial biopsy provides a safe, reliable, morphologic index of acute rejection and has an important role to play in the management of patients in whom acute rejection occurs. Repeated endomyocardial biopsies are well tolerated, permitting monitoring of acute rejection in cardiac recipients. Some patients have undergone over 30 serial biopsies.

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.

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.

The diagnostic criteria of myocarditis by endomyocardial biopsy.

The difficulties in diagnosing acute idiopathic myocarditis have been highlighted. Only about 30% of clinically suspected cases show morphologic evidence of an inflammatory infiltrate. Difficulties experienced in obtaining positive results include timing of the biopsy in relation to the acute symptoms of the patient, sampling error, and quantitative criteria.

Altered orientation of glycosaminoglycans and cellular changes in the tibial cartilage in the first two weeks of experimental canine osteoarthritis.

Changes in the cellularity and in the nature of the matrix were studied in the cartilages of the tibial plateau in experimentally induced arthritis in the dog, 7 and 14 days after section of the anterior cruciate ligament. Samples from the different regions of these cartilages were chilled and sectioned in a cryostat, with a variable microtome chuck to allow precise orientation of the specimens. The samples were examined by normal light microscopy, by microscopic interferometry, and by quantitative polarized light microscopy.

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.

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).

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%).

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.

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).

Fatal myocardial infarction following therapy with prothrombin complex concentrates in a young man with hemophilia A.

A fatal myocardial infarction in a 22-year-old man with hemophilia A and a factor VIII inhibitor is described. The catastrophic event occurred while the patient was receiving high doses of unactivated prothrombin complex concentrates. Autopsy examination revealed myocardial hemorrhage with no evidence of coronary artery disease or thrombosis.

Technetium-99m pyrophosphate in diagnosis of acute cardiac rejection in the rat with effect of cyclosporine: concise communication.

Tc-99m pyrophosphate (PPi) uptake has been measured in a rat model of heterotopic heart transplant at 5 days after transplantation. comparison of tracer uptake, as a ratio between the heterotopic transplanted heart and the recipient's native heart, was made in four groups of animals. Group 1, with transplants between animals of isogeneic strain showed a lower ratio, significantly different from the ratio in Group 2 in which transplants were between nonisogeneic animals.

Heart and lung transplantation for pulmonary hypertension.

Seventeen patients received combined heart and lung transplants at Stanford University between March 1981 and December 1983. All recipients were suffering from end-stage pulmonary hypertension. Five patients died within the first few postoperative weeks, but the remainder were well between 2 and 35 months after operation.

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.

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.

Telemetry of electrophysiologic variables from conscious dogs: system design, validation, and serial studies.

The necessity for conscious animal models in the study of cardiac physiology has been established for hemodynamics. The characterization of the electrophysiologic properties of the heart has not been performed in a serial fashion in a conscious animal model. Implanted telemetry sensing devices for recording atrial, ventricular, and His electrograms and stimulation systems for both atrium and ventricle allowed serial evaluation of eight dogs for up to 4 months.

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.

Clinical heart-lung transplantation.

Combined heart and lung transplantation was carried out in thirteen patients at Stanford University between March 1981 and May 1983. The recipients were between 22 and 45 years old. All patients were suffering from end-stage pulmonary hypertension; nine patients had Eisenmenger's syndrome; the remaining four were transplanted for primary pulmonary hypertension.

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.

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.

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.

Mediation of subacute anthracycline cardiotoxicity in rabbits by cardiac histamine release.

We tested the hypothesis that cardiac histamine release mediates subacute doxorubicin (DXR) cardiotoxicity in rabbits. New Zealand white rabbits given DXR 20 mg/kg i.v.