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Biomedical subjects

M E Billingham

Publications and source records attributed to M E Billingham.

At least 145 records · Page 8Linked to original sources
PubMed1987

Changes in Doppler echocardiographic indexes of left ventricular function as potential markers of acute cardiac rejection.

Changes in left ventricular filling and ejection as potential markers of cardiac allograft rejection were evaluated by serial Doppler echocardiography performed in 23 normal volunteers and within 24 hr of endomyocardial biopsy in 22 patients aged 14 to 53 years (mean 37). Peak aortic velocity, left ventricular ejection time index (ETI), isovolumic relaxation time (IVRT), mitral valve pressure half-time (PHT), peak early mitral flow velocity (M1), and velocity following donor atrial systole (M2) were measured without prior knowledge of endomyocardial biopsy findings. Biopsy specimens were graded histologically as: no rejection, mild rejection (cellular infiltrate), and moderate rejection (myocyte necrosis). A total of 120 biopsy-correlated Doppler echocardiographic studies were performed during 16 weeks after cardiac transplantation. Heart rate and mean arterial pressure were significantly higher in transplant recipients than in normal subjects. IVRT and PHT were significantly longer, while M1 and M2 were similar. Peak aortic velocity was higher in normal subjects than in transplant recipients, while ejection time was similar. Rejection of increasing severity was associated with a progressive shortening of IVRT and PHT and with an increase in M1 (p less than .0005 for all comparisons). Peak aortic velocity and ejection time index did not change significantly with rejection. These data indicate that acute cardiac rejection is accompanied by alteration in left ventricular filling dynamics detectable by Doppler echocardiography, without measureable changes in systolic function. These changes may provide noninvasive markers for surveillance of rejection.

Acute Disease↗
PubMed1987

Myocardial lymphocytes. Fact, fancy, or myocarditis?

The diagnosis of active lymphocytic myocarditis by the use of the endomyocardial bioptome is at present a hotly debated topic. However, the question of whether lymphocytes reside in the myocardium of individuals without systemic or cardiac disease has rarely been addressed, but is obviously of critical importance in helping to resolve this issue. Therefore, we examined endomyocardial biopsies obtained from 86 young heart disease-free cardiac transplant donors at the time of transplantation. Foci of inflammatory cells were found in eight (9.3%) cases and by definition contained greater than five inflammatory cells per focus. The inflammatory infiltrates were predominantly lymphocytic. Based on these results and those of others, it is becoming evident that there is a normal myocardial lymphocyte population which must be reckoned with when considering the diagnosis of myocarditis, realizing the potential therapeutic implications of this diagnosis.

Adolescent↗
PubMed1987

The surgical pathology of hypertrophic cardiomyopathy.

The pathologic diagnosis of hypertrophic cardiomyopathy (HCM) rests on the gross cardiac morphology and the presence and extent of myofiber disarray in the interventricular septum. Little attention, however, has been focused on the features of HCM in endomyocardial biopsy or septal myomectomy specimens. We therefore examined nine right ventricular biopsy specimens and 89 myomectomy specimens from 98 patients with clinically diagnosed HCM. Myofiber disarray was present in three (33%) of the biopsy specimens and 52 (58%) of the septectomy specimens. Associated findings in both specimen types included myocyte hypertrophy and interstitial fibrosis. The myomectomy specimens also frequently contained areas of patchy fibrosis, abnormally thick coronary arteries, and a fibrous endocardial plaque. When myofiber disarray was present in myomectomy specimens, it was confined to the deepest portion in 79% of the specimens, confirming that the disarray is frequently confined to the middle transverse third of the septum. Endomyocardial biopsy specimens may be used to suggest the diagnosis of HCM; however, because of their small size and their relatively nonspecific pathologic changes, they are of limited value in making the diagnosis of HCM. Septal myomectomy specimens usually contain pathologic findings consistent with HCM. The role of the surgical pathologist in the myomectomy cases is to confirm that these changes are present and are characteristic of the disorder.

Adult↗
PubMed1986

Enzymic heterogeneity of normal canine articular cartilage.

Articular cartilage is generally considered to be an homogeneous tissue. It has now been shown that, although different regions of the medial tibial cartilage of the dog have very similar oxidative enzymic activities, each region is heterogeneous with respect to these activities. The conventional histological delineation of this cartilage has been modified, to take into account a narrow band (designated zone 2a), just below the most superficial spindle-shaped cells, that has higher oxidative enzymic activity than any other. Changes in the activity in this zone might be diluted by the lack of change in other zones if measured by conventional biochemical procedures which could not measure the activities of the different zones separately.

Alcohol Oxidoreductases↗
PubMed1986

Doxorubicin cardiac toxicity manifesting seven years after treatment. Case report and review.

This report describes a patient treated for lymphoma who had development of doxorubicin (Adriamycin) cardiotoxicity proved by endomyocardial biopsy seven years after treatment. Doxorubicin cardiotoxicity is reviewed with emphasis on the implications of the long latency period for anthracycline cardiotoxicity in patients treated with this widely used antineoplastic agent.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Autologous pericardium versus a xenograft substitute in myocardial wound healing.

This study compared repair of myocardial wounds covered with autologous pericardium to healing of wounds covered with glutaraldehyde-preserved bovine pericardium in an experimental canine model. Right (RV) and left (LV) full thickness ventriculotomies were made and closed. In the control group (n = 12), the pericardium was closed over the wound; in the experimental group (n = 12), wounds were covered with bovine pericardium. Animals were sacrificed at 14, 21, 28, and 42 days. After excising the pericardium, 6 mm punch biopsies of normal RV, RV wound, normal LV, and LV wound were assayed for hydroxyproline (HPro). Both autologous and bovine pericardium became densely adherent to the wounds. Bovine pericardium was mildly adherent over unwounded areas, while autologous pericardium was usually free. Normal RV contained more than twice as much HPro as normal LV (5.4 +/- 0.57 micrograms/mg vs 1.7 +/- 0.35 micrograms/mg, P less than 0.0002). A gradual rise in HPro over time was seen in both groups, but this increase was statistically significant only at 42 days (P less than 0.05). There was no significant difference in HPro between wounds covered with autologous pericardium and those covered with bovine grafts (P = 0.13) at any of the sample times in this study. In this experimental canine model, the pericardium does not appear to play a prominent role in myocardial wound healing by contributing collagen-producing fibroblasts. Furthermore, the bovine pericardial xenograft becomes densely adherent to LV and RV incisions. In the clinical setting, such may make reoperation more hazardous when the heart has been previously incised or coronary bypass grafts have been constructed.

Animals↗
PubMed1986

Leukocytic infiltrates in idiopathic dilated cardiomyopathy. A source of confusion with active myocarditis.

The histologic criteria for the endomyocardial biopsy diagnosis of idiopathic dilated cardiomyopathy (IDCM) and active idiopathic/viral myocarditis are unclear. The present study was undertaken to characterize the nature of the inflammatory cell infiltrates in IDCM and thereby refine the differential diagnostic criteria for distinguishing IDCM from myocarditis using endomyocardial biopsy. We examined a mean of 6.2 large random sections from excised hearts of all cardiac transplant recipients at Stanford University with a diagnosis of IDCM, from June 1968 through June 1984. The 108 cases were evaluated for inflammatory cell type, extent, and location. Thirteen percent had no infiltrate, 32.5% had 1-5 foci of at least five inflammatory cells, 47% had 6-30 foci, and 7.5% had 30 or more foci. The infiltrates were primarily lymphocytic; while they were usually in the myocardial parenchyma, infiltrates were also located in zones of fibrosis, the endocardium, the epicardium, and surrounding vessels. Pretransplant biopsies in 56 of the 108 cases were available for review, and 55% of these contained inflammatory cell infiltrates. Agreement between the presence of infiltrates in the biopsy and the resected heart was obtained in 64%. This study highlights the high incidence of inflammatory cell infiltrates in the hearts of patients with IDCM. It reinforces the need for interpreting lymphocytic infiltrates in an endomyocardial biopsy with caution, as their mere presence does not necessarily imply a diagnosis of active myocarditis.

Adolescent↗
PubMed1986

The morphological progression of viral myocarditis.

In an attempt to document the morphological progression from acute idiopathic myocarditis to end-stage dilated cardiomyopathy we studied 20 patients with a diagnosis of myocarditis who had had serial endomyocardial biopsies performed with intervals of 1 month to 2 years and whose ages varied from 6 months to 62 years. Fifteen of these patients were treated with immunosuppressive drugs for myocarditis. Ten out of 15 treated patients stabilized clinically. In the remaining 5 cases there was worsening congestive heart failure and 1 patient underwent cardiac transplantation. Of the 5 patients who did not receive immunosuppression, 2 stabilized spontaneously, and 3 developed heart failure, 2 of whom subsequently had cardiac transplants. Whether the patients received immunosuppression or not, in all cases, the inflammatory infiltrate was less but the myocardium developed significant hypertrophy with an increase in interstitial fibrosis and in 8 cases the morphological changes were those of dilated cardiomyopathy. From the morphological standpoint of this study we have shown some evidence that dilated cardiomyopathy can be the end result of acute myocarditis. It appears that not every case of acute myocarditis progresses to dilated cardiomyopathy and that steroid treatment does not necessarily prevent progression of myocarditis to dilated cardiomyopathy.

Acute Disease↗
PubMed1986

Primary pulmonary hypertension and pregnancy.

Despite the preponderance of primary pulmonary hypertension (PPH) in young female subjects, documented cases of PPH in association with pregnancy are uncommon. During a 12-month period, 73 female patients with PPH were evaluated as potential recipients of a heart-lung transplant; and in six (8 percent), PPH appeared to be related to pregnancy. Histologic confirmation of the diagnosis was available in four patients, and other causes of pulmonary hypertension were excluded as far as possible in the remaining two patients.

Adolescent↗
PubMed1986

Combined heart-lung transplantation for end-stage Eisenmenger's syndrome.

Between May, 1981, and December, 1984, thirteen combined heart-lung transplants were performed in 12 patients for the treatment of Eisenmenger's syndrome. The age range of the recipients was 22 to 42 years. Two patients had undergone previous open cardiac operations; in addition, one had had closure of a persistent ductus arteriosus, one an open lung biopsy, one a pulmonary artery banding, and one patient received a second heart-lung transplant after 3 years. Four recipients died before hospital discharge, one at operation and three at 4, 10, and 33 days after operation. Early symptomatic results and cardiopulmonary function were excellent in all of the survivors. Two patients died 14 and 15 months after transplantation of accelerated graft arteriosclerosis and respiratory failure, respectively, and six remain alive 7 to 44 months after transplantation. Four of these surviving patients and the two patients who died late subsequently had major pulmonary complications. Symptoms included progressive breathlessness, cough (often productive), and fever with physical signs of diffuse crepitations and expiratory rhonchi. Serial pulmonary function tests showed progressive obstructive physiology in all six patients with superimposed restrictive defects in four. Histologic examination of tissue from open lung biopsy or autopsy displayed bronchiolitis obliterans in five of these patients, one of whom required retransplantation. It is possible that these late changes are the result of rejection, since similar changes in one other patient have now been reversed with augmented immunosuppression. Further understanding of the causes and manifestations of late pulmonary deterioration should improve the late functional results of this operation for Eisenmenger's syndrome.

Adult↗
PubMed1985

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. This can be explained by the synthesis in osteoarthritic cartilage of abnormally long chondroitin sulphate chains on newly synthesised proteoglycans. The extracts also contained a newly formed small proteoglycan species that was unable to interact with hyaluronic acid. The proportion of this species was higher in osteoarthritic cartilage compared with normal, examined 3 weeks after surgery, but was generally absent from cartilage obtained 3 and 6 months after surgery. Compared with controls, a smaller proportion of the (35S)-proteoglycans released into the maintenance medium of explant cultures of osteoarthritic cartilage during a 48 h chase period was able to interact with hyaluronic acid. However, although furnished with longer (35S)-glycosaminoglycan chains, these proteoglycans were smaller than those from control explants.

Animals↗
PubMed1985

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. The orientation of the glycosaminoglycans was assessed by the new "induced birefringence" method. The results indicated that only the region of the medial tibial cartilage that was unprotected by the meniscus was affected, showing increased water content, loss of superficial cells, and a decrease in orientation of the glycosaminoglycans. Whereas the birefringence of the collagen was unaffected, the superficial area that lacked oriented glycosaminoglycans was markedly increased; this may be a useful indicator of early osteoarthritic changes.

Alcian Blue↗
PubMed1985

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. Adequate sampling requires at least four pieces of tissue. The biopsies are graded in the following manner: Mild acute rejection is characterized by a perivascular and mild interstitial infiltrate of pyroninophilic lymphoblasts without myocyte necrosis. Moderate acute rejection has an increased infiltrate extending into the interstitium and causing focal myocyte necrosis. This requires augmentation of immunosuppression. Severe acute rejection, which is more difficult to reverse, includes a more prolific infiltrate with the addition of neutrophils, hemorrhage, and increased myocyte necrosis. Ongoing acute rejection implies that the degree of acute rejection is the same, or worse, than the previous biopsy. Resolving or resolved acute rejection shows reparative changes with diminishing or absent inflammatory infiltrate following treatment. Recipients treated with Cyclosporin-A develop rejection and respond to treatment more slowly than with conventional treatment. This group also develops endocardial infiltrates and a dose-related fine perimyocytic cardiac fibrosis. The endomyocardial biopsy is also useful in identifying infectious agents, for example, toxoplasmosis in cardiac recipients.

Acute Disease↗
PubMed1985

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. In addition, pressure from the referring physician may influence the pathologic interpretation, i.e., in making a morphologic diagnosis on slender evidence. Caution is also necessary in the interpretation of end-stage disease of dilated cardiomyopathy and "chronic myocarditis." This is important as it influences therapy with immunosuppressive agents. The importance of obtaining a detailed history of drugs to which the patient might have been exposed and can result in myocarditis is also stressed. Only if an accurate and unbiased pathologic evaluation can be made will a prospective, randomized multicenter trial yield useful information. The Dallas Myocarditis Panel has set forth useful criteria and guidelines in an attempt to classify the morphologic diagnosis of myocarditis. Semantic and diagnostic criteria for myocarditis can still be challenged, but the Dallas criteria for evaluation does allow an accurate assessment by all pathologists, in spite of individual variation.

Biopsy↗