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Biomedical subjects

M E Billingham

Publications and source records attributed to M E Billingham.

At least 217 records · Page 12Linked to original sources
PubMed1978

Doxorubicin cardiotoxicity. Serial endomyocardial biopsies and systolic time intervals.

Doxorubicin, whose dose-limiting toxicity is cardiomyopathy, was given to four cancer patients. Endomyocardial biopsy specimens and test results of cardiac function were obtained before, during, and after treatment. The biopsy specimens were examined by light and electron microscopy and were graded blindly. Evidence of specific doxorubicin injury was found in 3/4 patients with as little as 180 mg/sq m of the drug and became progressively more severe with higher doses. All test results of cardiac function, including systolic time intervals, remained normal. These data suggest that a specific, progressive subclinical injury to the heart occurs with doxorubicin therapy, which cannot be reliably detected by routine tests. This potential risk must be taken into account with the use of doxorubicin, especially when combined with synergistic agents.

Adult↗
PubMed1978

Cardiac biopsy evidence for a cardiomyopathy associated with symptomatic mitral valve prolapse.

Right ventricular endomyocardial biopsy was performed in 14 patients with mitral valve prolapse to determine the existence of an associated cardiomyopathic process. All 14 patients had echocardiographic, angiographic or auscultatory evidence of mitral valve prolapse, and all were symptomatic. The group had a high incidence rate of conduction system abnormalities (50 percent) and arrhythmias (64 percent), but only one patient had a significant hemodynamic abnormality. Light microscopy revealed an increase in endocardial and interstitial fibrosis in eight patients (57 percent). Electron microscopy, performed in 11 patients, showed mitochondrial degenerative changes in all 11. Nuclear chromatin clumping, intracell edema and myocyte degeneration were frequently present. It is concluded that endomyocardial and myocardial abnormalities exist in some symptomatic patients with idiopathic mitral valve prolapse.

Adult↗
PubMed1978

Structural changes in glutaraldehyde-treated porcine heterografts used as substitute cardiac valves. Transmission and scanning electron microscopic observations in 12 patients.

Scanning and transmission electron microscopic studies were made of (1) 12 glutaraldehyde-treated porcine valvular heterografts that had been implanted in patients for 2 days to 76 months; (2) 3 unimplanted commercially processed porcine aortic valves; and (3) 1 unprocessed porcine aortic valve. Comparison of unprocessed porcine valves and unimplanted commercially processed valves showed loss of endothelium and acid mucopolysaccharides during preimplantation processing. Short-term (less than 2 months) changes after implantation consisted of insudation of plasma proteins, penetration of erythrocytes into surface crevices, formation of a thin surface layer of fibrin, and deposition of macrophages, giant cells and a few platelets. Longer-term (more than 2 months) changes were proportional to the time interval after implantation and consisted of progressive disruption of collagen, erosion of the valve surfaces, formation of aggregates of platelets and accumulation of lipid. The surfaces of the leaflets did not become covered with endothelium or with a fibrous sheath. Calcific deposits were found in one valve and bacterial organisms in another. Thus, progressive breakdown of collagen appears to be a critical factor in determining the long-term durability of glutaraldehyde-treated porcine valvular heterografts.

Adult↗
PubMed1978

Diverticulum of the left ventricle in hypertrophic cardiomyopathy.

An unusual case of diverticulum of the left ventricle is presented. The most distinctive feature was the presence of a circumferential mid-ventricular contraction ring with histologic abnormalities similar to those described in patients with asymmetric septal hypertrophy. This abnormal ring of tissue obstructed emptying of the ventricular apex and isolated it from the rest of the ventricle. The obstructed apex assumed the appearance of a muscular diverticulum, and the residual portion of the ventricle was markedly diminished in volume. In addition, the abnormal mid-ventricular hypertrophy interfered with papillary muscle function, producing mitral valve prolapse and mitral regurgitation. The patient's age was equally unusual; she was 65 at the time of diagnosis, probably the oldest known patient with ventricular diverticulum. She was treated surgically by transapical myotomy and myectomy of the mid-ventricular contraction ring, in order to increase effective ventricular volume. The relationship of this entity to other types of ventricular deiverticula and aneurysms, and to hypertrophic cardiomyopathy, is discussed.

Aged↗
PubMed1978

Early anthracycline cardiotoxicity.

Eight patients in whom cardiac dysfunction developed within four weeks of receiving their first or second course of daunorubicin or doxorubicin are described. Four patients presented with pericarditis; three of these four had evidence of myocardial dysfunction. Histopathologic analysis of these patients was consistent with an acute myocyte damage and secondary inflammatory process. An additional group of four patients presented with symptoms and signs of heart failure. These patients were either elderly or had evidence of previous cardiac disease. One of these patients suffered a myocardial infarction 24 hours after receiving 60 mg/m2 of daunorubicin; earlier doses in the same course had been associated with evidence of myocardial ischemia. We conclude that anthracycline antibiotics may manifest clinically significant cardiotoxicity at total cumulative doses much less than have been associated with chronic cardiomyopathy.

Adult↗
PubMed1978

Doxorubicin cardiomyopathy: evaluation by phonocardiography, endomyocardial biopsy, and cardiac catheterization.

Right ventricular endomyocardial biopsy, right heart catheterization, and systolic time intervals were done in 33 adult patients receiving doxorubicin (AdriamycinTM). Doxorubicin administration was associated with a dose-related increase in the degree of myocyte damage, and 27 of 29 patients biopsied at doses greater than or equal to 240 mg/m2 had doxorubicin-associated degenerative changes identified on biopsy. The pre-ejection period to left ventriculr ejection time ratio (PEP/LVET) showed a threshold phenomenon and did not begin to increase until a total dose of 400 mg/m2 had been reached. Seven patients with catheterization-proven heart failure had a significantly greater amount of myocyte damage on biopsy than dose-matched control subjects (P less than 0.01). Preveious mediastinal radiation appeared to potentiate the doxorubicin-associated degenerative process. Mediastinal radiation and age greater than or equal to 70 years appeared to be risk factors for doxorubicin-associated heart failure. Dose limitation by combined clinical, noninvasive, invasive, and morphologic criteria offered an advantage over empirical dose limitation or dose limitation by PEP/LVET alone.

Adult↗
PubMed1978

Ultrastructure of Hancock porcine valvular heterografts. Pre- and post-implantation changes.

Scanning and transmission electron microscopic studies were made of: 1) 15 glutaraldehyde-treated porcine valvular heterografts that had been implanted in patients for periods of time ranging from 2 days to 76 months; 2) unimplanted, commercially processed porcine aortic valves; and 3) unprocessed porcine aortic valves. Unimplanted, commercially processed valves showed loss of endothelium and acid mucopolysaccharides. Short-term (< 2 months) post-implantation changes consisted of insudation of plasma proteins, penetration of erythrocytes into surface crevices, formation of a thin surface layer of fibrin, and deposition of macrophages, giant cells and a few platelets. Longer term (> 2 months) changes consisted of progressive disruption of collagen, erosion of valvular surfaces, formation of aggregates of platelets, and accumulation of lipid. The surfaces of the leaflets did not become covered with endothelium or with a fibrous sheath. It is concluded that progressive breakdown of collagen is a critical factor in determining the long-term durability of glutaraldehyde-treated porcine valvular heterografts.

Animals↗
PubMed1978

Invasive and noninvasive methods of assessing adriamycin cardiotoxic effects in man: superiority of histopathologic assessment using endomyocardial biopsy.

Endomyocardial biopsies and cardiac catheterizations were performed in 55 patients treated with adriamycin (ADM). Eleven patients underwent serial invasive studies. In addition, most of these patients had systolic time interval determinations, echocardiograms, and electrocardiograms at the time of catheterization. The relationship of these various tests to cumulative dose of ADM and to the incidence of cardiac dysfunction was analyzed. Only pathologic assessment of ADM-induced myocardial damage showed a progressive stepwise increase in severity at successively higher doses of ADM. In addition, the incidence of myocardial dysfunction correlated well only with pathologic findings on biopsy. We conclude that standard noninvasive methods of assessing ADM cardiotoxicity are inadequate and that histopathologic assessment by means of endomyocardial biopsy is a valuable, reliable, and accurate technique.

Adult↗
PubMed1978

Anthracycline cardiomyopathy monitored by morphologic changes.

Seventy-six endomyocardial biopsies obtained from 60 patients receiving adriamycin (ADM) and other anthracycline analogs were studied. The biopsies were studied by light and electron microscopy. Two main types of myocyte degeneration were consistently present, the lesions were focal, and inflammatory infiltrate was absent. The severity of pathologic changes was graded on a scale from 0 (normal) to 3 (marked abnormality). Twelve patients receiving previous mediastinal irradiation (600-5700 rads) showed a mean pathology grade (2.0 +/- 0.89) that was significantly higher than in those patients receiving a comparable dose of ADM but who were not irradiated (1.18 +/- 0.23) (P less than 0.01). This study indicated that radiation, even if remote, enhances ADM-induced cardiotoxicity and evokes a "recall" phenomenon of latent acute irradiation changes. Our data suggest that a specific, progressive, subclinical injury to the heart occurs with anthracycline therapy that cannot be detected reliably by conventional tests. Anthracycline-induced cardiotoxicity in rabbits, monkeys, and dogs shows the same basic cellular lesions as in man. The analogs, adria-DNA and rubidazone, also show lesions similar to those produced by ADM in the human heart. The endomyocardial biopsy is a reliable method for monitoring cardiac damage due to anthracyclines in man.

Adult↗
PubMed1978

Clinical spectrum of anthracycline antibiotic cardiotoxicity.

Anthracycline derivatives may produce early or late cardiotoxic reactions in man. Early effects include: (a) pericarditis-myocarditis which can affect patients with no previous history of cardiac disease and which carries a high mortality rate ( approximately 20%); (b) left ventricular dysfunction which may lead to clinically significant heart failure in patients with limited cardiac reserve; and (c) arrhythmias, the most common of which is sinus tachycardia. Symptomatic supraventriclar tachycardia, heart block, and ventricular arrhythmias can occur, however, and may reflect primary effects on cardiac muscle or the conduction system. Late effects of anthracyclines are directly related to the degree of associated myocyte damage and include subclinical left ventricular dysfunction and overt heart failure. The implications for prognosis and further treatment are discussed for each of these entities and a common pathogenetic mechanism is proposed.

Adolescent↗
PubMed1977

Correlative study of regional left ventricular histology and contractile function.

In 110 patients with documented coronary artery disease, transmural biopsy of the anteroapical region of the left ventricle was performed during aortocoronary bypass grafting. Biopsy specimens were semiquantitatively graded microscopically for myocardial fibrosis as an indicator of chronic ischemic damage. Preoperatively, systolic wall motion of the region from which the biopsy specimen was taken was semiquantitatively graded as showing normal motion, hypokinesia, akinesia or dyskinesia on ventriculography. Wall motion-histologic correlations, taking into account both electrocardiographic evidence of anterior infarction and ST-T abnormalities, were then established. Overall, there was fair agreement (72 percent) between functional and histologic assessment of the left ventricular region evaluated, both qualitatively (normal versus abnormal, 72 percent agreement) and quantitatively (degree of abnormality, correlation coefficient 0.66, P = 0.005). The 22 patients with electrocardiographic evidence of anterior infarction had various degrees of abnormal regional motion and myocardial fibrosis. Discordance between wall motion and histologic findings was most common (50 percent of instances) in the 34 patients with anterior ST-T changes without infarction and generally was manifest as abnormal motion with normal histologic features. By contrast, normal motion and abnormal histologic features represented the most common type of discordance (22 percent of instances) in the 54 patients without either anterior infarction or ST-T deviation. These data provide a basis for inference of myocardial morphologic features (fibrosis) from assessment of ventriculographic wall motion and the electrocardiogram. They may thus be useful in predicting the potential functional benefits of bypass grafting of coronary arteries supplying abnormally contractile segments of the left ventricle.

Adult↗
PubMed1977

Methysergide-induced heart disease: a case of multivalvular and myocardial fibrosis.

Methysergide (Sansert) is known to cause mitral and aortic valvular fibrosis and dysfunction, but has generally not been known to damage right heart valves or the myocardium, and cardiac fibrosis has not been considered to be a risk if therapy is intermittently interrupted. The woman who is the subject of this case report developed catheterization-proven severe tricuspid and moderate aortic and mitral regurgitation during noncontinuous therapy with methysergide. In addition, right ventricular endomyocardial biopsy revealed extensive endocardial and intramyocardial fibrosis.

Aortic Valve Insufficiency↗
PubMed1977

Adriamycin cardiotoxicity: endomyocardial biopsy evidence of enhancement by irradiation.

Endomyocardial biopsies were examined in 12 patients receiving total doses of Adriamycin from 90 to 445 mg/M2. These patients had also received previous mediastinal irradiation (from less than 600 to 5700 rad) over periods varying from 6 months to 14 years prior to the endomyocardial biopsy. Severity of pathological change in these 12 patients was compared with that of dose-matched control patients who had not received mediastinal radiation. The severity of the histopathologic changes was scored on a scale from 0 (normal) to 3 (marked abnormality). The mean score of the group receiving irradiation (2.0 +/- 0.89) was significantly higher than the score in those not irradiated (1.18 +/- 0.23) (p less than 0.001). Morphological demonstration of a "recall phenomenon" of latent radiation changes by Adriamycin was demonstrated in small intramyocardial vessels. This study indicates that radiation, even if remote, enhances Adriamycin-induced cardiomyopathy. Therefore, Adriamycin must be given cautiously in patients who have received previous mediastinal radiotherapy.

Adult↗
PubMed1976

The role of the acute phase reaction in inflammation.

Inflammation and injury to tissue results in a variety of local and systemic events, however although the local events of oedema formation and cellular infiltration have received considerably more attention the systemic response to inflammation is no less profound. The particular systemic event which forms the substance of this communication is the change in the circulating levels of plasma proteins which occurs after inflammatory injury, and the manner in which these changes in plasma concentration are controlled by changes in plasma concentration are controlled by changes in the rate of synthesis. A discussion of the role of the liver in controlling inflammatory events, in relation to the synthesis of an anti-inflammatory protein has been given; the present work is an extension of this and describes the changes in concentration and synthesis rate of albumin, fibrinogen and alpha1 acid glycoprotein during adjuvant arthritis in the rat. The changes which occur are regulated at the liver by alteration of the rate of synthesis of the individual protein. For example albumin at the height of adjuvant arthritis falls to a third of its normal plasma level whereas the level of alpha1 acid glycoprotein increases up to twenty-fold; these changes are reflected by similar changes in their synthesis rate by the liver. The effect of the fall in albumin concentration on the plasma binding of anti-inflammatory drugs (and their toxicity) in relation to these findings will be discussed along with the biological role of the acute phase plasma proteins and hence the influence of the liver in the response to injury.

Animals↗
PubMed1975

Left atrial myxoma: diagnosis, treatment, and cytological observations.

A patient first seen with cardiac cachexia was found to have a large left atrial myxoma. The diagnosis was first suggested by echocardiographic examination. Cure was achieved by surgery. Light and electron microscopic studies indicate a multipotential mesenchymal cell origin of myxomata.

Cardiac Catheterization↗
PubMed1975

Cytology of the cerebrospinal fluid in patients with Hodgkin's disease or malignant lymphoma.

The cerebrospinal fluids (CSF) of 18 patients with Hodgkin's disease and 33 patients with malignant lymphoma were evaluated for the presence of malignant cells. The CSF cytology was correlated with the neuropathologic findings at surgery or autopsy. In the 51 patients included in the study there were seven false-negative CSF cytodiagnoses. Methods to improve detection in the false-negatives will be discussed. There were two false-positives. Explanations for the two false-positive cytodiagnoses will be presented. It is concluded that cytological examination of the CSF in patients with Hodgkin's disease and malignant lymphoma is a useful and reliable diagnostic tool.

Cerebrospinal Fluid↗