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Biomedical subjects

A E Becker

Publications and source records attributed to A E Becker.

At least 109 records · Page 6Linked to original sources
PubMed1993

Is the Watanabe heritable hyperlipidemic rabbit a suitable experimental model for percutaneous transluminal coronary angioplasty in humans? A light microscopic, immunohistochemical and ultrastructural study.

OBJECTIVES: This study was designed to assess an experimental model for the study of mechanisms that underlie restenosis after percutaneous transluminal coronary angioplasty. BACKGROUND: The Watanabe heritable hyperlipidemic (WHHL) rabbit lacks the receptor for low density lipoproteins, produces atherosclerotic lesions very similar to those in humans and, therefore, could serve as a suitable model. METHODS: Percutaneous transluminal angioplasty was performed on the left subclavian artery of 10 homozygous rabbits. The animals were killed at a few hours or 3, 7, 14 or 28 days after the procedure. The artery was fixed by perfusion, and the site of angioplasty was examined by both light and electron microscopy with the use of conventional and immunohistochemical staining techniques. RESULTS: Angioplasty had caused a flap-like or dissecting tear into the media. At day 3, cells within the preexisting media adjacent to the injury had the ultrastructural characteristics of synthetic smooth muscle cells. At day 7, spindle cells at the site of injury stained either negative or very weakly positive with a marker for actin; ultrastructurally, these cells had the synthetic phenotype. At day 14, the spindle cells showed a mix of contractile and synthetic phenotypes. The surface was partially covered by endothelial cells. At day 28, the dominant cell type was the contractile smooth muscle cell and the surface was completely covered by endothelial cells. CONCLUSIONS: Both the injury and the response to injury after percutaneous transluminal angioplasty were almost identical to that seen in humans after coronary angioplasty. Thus, the WHHL rabbit appears to be an appropriate experimental model for use in further studies.

Angioplasty, Balloon, Coronary↗
PubMed1993

Angiographic-pathologic correlations after elective percutaneous transluminal coronary angioplasty.

BACKGROUND: The local effect of coronary angioplasty is evaluated on the basis of postangioplasty angiograms. Smooth-walled dilation is considered to represent minimal or no injury, whereas intraluminal haziness corresponds with wall laceration. This study correlates the preangioplasty and postangioplasty angiograms with the histopathology of the target sites. METHODS AND RESULTS: The study includes 12 patients, each undergoing an elective procedure, and covers 19 angioplasty sites. Smooth-walled dilation and intraluminal haziness were not mutually exclusive. The angiograms were interpreted as smooth-walled dilation (n = 3), smooth-walled dilation with intraluminal haziness (n = 4), intraluminal and extraluminal haziness (n = 5), extraluminal dissection (n = 5), spiraltype dissection (n = 1), and aneurysm (n = 1). The histology of the arterial segments revealed wall laceration in all. Smooth-walled dilation without intraluminal haziness correlated with laceration limited to the intima in two, but with medial injury in one. Smooth-walled dilation with intraluminal haziness correlated with laceration limited to the intima in two and with medial injury in two. Intraluminal and extraluminal haziness corresponded with extensive laceration with deep involvement of the media in each. Extraluminal dissection correlated with a dissection along the shoulder area of the plaque, creating a broad-based flap. The spiral-type dissection corresponded with a true dissection into the plaque-free media. The aneurysm correlated with partial washout of an atherosclerotic plaque. CONCLUSIONS: The angiographic image of intraluminal and extraluminal haziness indicates extensive medial laceration. Smooth-walled dilation, with or without intraluminal haziness, is not a reliable indicator. The study emphasizes the need to reconsider the interpretations of postangioplasty coronary angiograms.

Aged↗
PubMed1993

Is there an anatomic basis for subvalvular right ventricular outflow tract obstruction after an arterial switch repair for complete transposition? A morphometric study and review.

The study was initiated by reports on right ventricular outflow tract obstruction in complete transposition of the great arteries after an arterial switch repair. We investigated 39 heart specimens with native, unoperated transposition of the great arteries. Of these, 14 hearts had a ventricular septal defect; 25 had an intact ventricular septum. In each heart specimen the narrowest site of the subaortic outflow tract was measured and compared with the circumference of the aortic orifice. Obstruction was considered to be present if the outflow tract circumference was less than that of the aortic orifice. In addition, the diameter of the ascending aorta immediately above the level of the valve orifices was measured and compared with that of the pulmonary trunk. An obstruction was present in the subaortic right ventricular outflow tract of two hearts (5.1%): one of the obstructions, in a neonatal heart with intact ventricular septum, was caused by a prominent supraventricular crest and anterior trabeculations; the other obstruction was an additional extensive muscular hypertrophy, in the heart of a 13-year-old patient with a similar anatomy, and a septal defect. A mismatch between the diameters of the ascending aorta and the pulmonary trunk was present in 15 of 32 hearts measured. Our observations and a review of the literature confirm that subvalvular right ventricular outflow tract obstruction in hearts with native transposition of the great arteries is infrequent. Nevertheless, the anatomic characteristics of the right ventricular outflow tract are such that the tract is intrinsically narrow and muscular hypertrophy may easily lead to obstruction. After an arterial switch operation, subvalvular obstruction could be caused by dynamic processes analogous to those observed after relief of isolated pulmonary valve stenosis. Anatomic subvalvular obstruction could be due to either an obstruction that was not identified before operation or (a purely speculative hypothesis) subtle degrees of mismatch in size between the proximal aorta and the pulmonary trunk, which may be considered irrelevant at time of operation but may also set into pace a process of ongoing adaptive infundibular hypertrophy.

Academic Medical Centers↗
PubMed1992

An immunocytochemical analysis of rapidly progressive atherosclerosis in human vein grafts.

Aortocoronary vein grafts are known to develop atherosclerotic plaques usually superimposed on intimal hyperplasia. The cellular characteristics of these lesions have been studied with immune cytochemical techniques and compared with those in native coronary arteries. Fifteen stenosed grafts showed concentric intimal hyperplasia characterized by massive proliferation of smooth muscle cells (HHF-35+). The subendothelial layer contained numerous T lymphocytes (UCHL-1+, MT-1+) and to a lesser extent macrophages (HAM-56+). Eleven grafts had superimposed atherosclerotic plaques characterized by atheroma but otherwise showing the same cellular constituents. The atherosclerotic plaques in the venous grafts resembled those in the coronary arteries, the main difference being the occurrence of multiple atheromas (up to 4 in a single section), the high number of T lymphocytes and macrophages related to these sites and the presence of atheromas bordering directly onto the luminal surface. It thus appears that the development of atherosclerotic plaques in vein grafts is accompanied by a similar immune inflammatory reaction as in native coronary atherosclerosis, presumably in a more aggravated form. The latter phenomenon could relate to the more enhanced and rapidly progressive nature of vein graft atherosclerosis.

Arteriosclerosis↗
PubMed1992

Aortic valve regurgitation and the congenitally bicuspid aortic valve: a clinico-pathological correlation.

OBJECTIVE: To investigate the morphology of congenitally bicuspid aortic valves causing pure valve regurgitation. DESIGN: A case series collected over five years. SETTING: An academic hospital. PATIENTS AND METHODS: One hundred and forty eight excised congenitally bicuspid aortic valves. The morphological findings were correlated with sex, age, clinical history, and data on haemodynamic function before operation. Pure valve regurgitation was defined as grade 3-4/4 with a gradient less than 30 mm Hg. Aortic root dilatation was evaluated angiographically or echocardiographically or both. RESULTS: Three types were recognised: valves that were purely bicuspid (23%), bicuspid valves with a raphe (34%), and valves with an additional indentation of the free edge of the conjoined cusp (43%). In 14 cases pure valve regurgitation was present. Dilatation of the aortic root was present in 47 cases. The relative risk for regurgitation when the aortic root was dilated (compared with no dilatation) was 3.99. The relative risk for valve regurgitation when there was indentation of the conjoined cusp (compared with no indentation) was 4.95. The mean age at operation in patients with pure regurgitation was 56 years, which is significantly younger (p = 0.0008) than that of patients with a congenitally bicuspid valve with combined valve stenosis and regurgitation (64.7 years). CONCLUSIONS: Congenitally bicuspid aortic valves with a central indentation of the free edge of the conjoined cusp seem particularly likely to develop pure aortic valve regurgitation.

Adult↗
PubMed1992

Adhesion molecules on the endothelium and mononuclear cells in human atherosclerotic lesions.

Atherosclerotic lesions show features of a cell-mediated immune inflammatory process. From this viewpoint, the potential role of arterial endothelium in the recruitment of mononuclear cells (T lymphocytes and macrophages) was studied. The endothelium of diffuse intimal thickening (DIT) and atheromatous plaques (AP) in human coronary arteries and abdominal aortas was characterized for the expression of adhesion molecules ELAM-1, ICAM-1, and the major histocompatibility complex (MHC) class II antigens HLA-DR/DP. A marked increase in expression of ICAM-1 and ELAM-1, and to a lesser extent HLA-DR/DP was observed on endothelial cells that were adjacent to subendothelial infiltrates of T lymphocytes (CD3+, CD11a+, HLA-DR/DP+) and macrophages (CD14+, CD11a+, CD11c+, HLA-DR/DP+). This contrasted with a lower or absent expression of these activation markers at sites without prominent inflammatory cell infiltrates. These findings could be demonstrated in DIT as well as in AP. The observations suggest that cytokines produced by the subintimal infiltrates may activate the endothelium in a similar way as is observed in the microvasculature at sites of immune inflammation. The expression of these activation markers in the microvasculature is associated with enhanced leukocyte adhesion, permeability for macromolecules, and procoagulant activity, features known to occur also in early experimental atherosclerosis. The findings therefore support the concept that arterial endothelium plays an active role in the recruitment of mononuclear cells in atherosclerotic lesions.

Adult↗
PubMed1992

Macrophage differentiation in atherosclerosis. An in situ immunohistochemical analysis in humans.

The differentiation of macrophages present in diffuse intimal thickening, fatty streaks, and atheromatous plaques, was analyzed with immunohistochemical methods, using segments of aorta, coronary, and carotid arteries obtained at autopsy. Various differentiation antigens were studied with the monoclonal antibodies anti-HLA-DR, EBM-11, Leu M3, OKM1, and OKM5. Adjacent sections were stained for lipids (oil red O) and lysosomal activity (acid phosphatase). Almost all macrophages identified with the pan-macrophage antibody EBM-11, also stained with the anti-HLA-DR antibody. Diffuse intimal thickening showed a predominance of Leu M3+ cells; fatty streaks also showed OKM1+ and OKM5+ macrophages. Classical atheromatous plaques showed a gradual shift in phenotypic expression towards the center of the lesion. Cells in the superficial layers were positive only with Leu M3, deeper localized cells showed double expression of Leu M3 and OKM1 or double expression of OKM1 and OKM5. Cells that were localized adjacent to the atheromatous debris stained only with OKM5. The phenotypic changes occurred in parallel with an increase in both fat uptake and lysosomal activity of the macrophages. This shift in phenotypic expression suggests a process of differentiation and maturation of the macrophages involved. The results indicate that macrophages within the arterial intima are activated and mature towards cells that express receptors for adhesion proteins and complement during the development of atherosclerotic plaques. This may imply that the macrophages involved in lipid metabolism also have a potential to act as effector cells in a chronic inflammatory process, and thus, may contribute to the progression of an atherosclerotic plaque. Functional studies of macrophage subpopulations are needed to verify this hypothesis.

Acid Phosphatase↗
PubMed1991

Chronic non-ischaemic congestive heart disease and endomyocardial biopsies. Worth the extra?

The diagnostic yield of endomyocardial biopsies in patients with chronic congestive heart failure of non-ischaemic aetiology remains questionable and, therefore, the use of endomyocardial biopsies under such circumstances is at stake. The present report documents the correlation between the histologic interpretation of endomyocardial biopsies and the corresponding cardiac explants in 13 patients who underwent cardiac transplantation. The biopsy diagnoses in these patients varied from 'compatible with dilated cardiomyopathy' (n = 6) to 'non-conclusive' (n = 4), 'ischaemia' (n = 2) and 'borderline myocarditis' (n = 1). Correlation with the corresponding cardiac explants revealed hypertrophy of myocytes as the leading histologic feature in the majority of cases. Because of the non-specific histopathology of dilated cardiomyopathy, the discrepancy between biopsy diagnoses and the leading explant diagnosis is mostly a matter of semantics. Ischaemia was present at high incidence, but is considered a result of imparied myocardial perfusion rather than the prime mechanism of heart failure. In four cardiac explants myocarditis was encountered, while the corresponding biopsies showed no cellular inflammation. In two, the cellular infiltrates suggested an early state of repair. One heart contained an active and extensive lymphocytic myocarditis. The fourth case showed an eosinophilic myocarditis, most likely acquired after the biopsy was taken. These discrepancies almost certainly relate to the sampling error and the time interval between biopsy and onset of symptoms. The immediate diagnostic yield of the biopsy, in this particular subset of patients, was minimal, particularly with respect to the diagnosis 'myocarditis'. Nevertheless, biopsy diagnoses such as 'compatible with' and 'non-conclusive' do contribute to the final categorization and management of these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

In vitro balloon dilatation of mitral valve stenosis: the importance of subvalvar involvement as a cause of mitral valve insufficiency.

To investigate the mechanism that increases the orifice area of the mitral valve during balloon dilatation 43 surgically excised intact rheumatic mitral valves were studied. The main pathological features were (a) fibrosis of mitral valve leaflets and commissures (10 valves); (b) fibrosis with calcification of one commissure (eight anterolateral, seven posteromedial); (c) fibrosis with calcification of both commissures (seven valves); and (d) predominant involvement of the subvalvar apparatus (11 valves). The valves were assessed by photography and radiography before and after balloon dilatation (balloons up to 38 mm (bifoil 2 x 19 mm) and pressures up to 4 atmospheres). The valve was dilated in stages under direct visual control by balloons of increasing diameter. Splitting of the fused commissures was the most common mode of widening the orifice. However, the mitral valve leaflets were torn in two fibrotic valves and in six valves with extensive involvement of the subvalvar apparatus. In the fibrotic valves (group (a] the tear originated near the valve perimeter, at the thinnest part of the remaining valve leaflet. In the valves with subvalvar involvement splitting started at the apex of spaces between the fused chordal columns and proceeded upward. Where there is extensive involvement of the subvalvar apparatus in rheumatic mitral valve disease the risk of tearing of the valve leaflets by balloon dilatation is increased and this is likely to predispose to the development of acute valvar insufficiency.

Calcinosis↗
PubMed1991

Fibrocellular tissue response after percutaneous transluminal coronary angioplasty. An immunocytochemical analysis of the cellular composition.

BACKGROUND: Restenosis after initial, successful percutaneous transluminal coronary angioplasty (PTCA) is due to fibrocellular proliferation. METHODS AND RESULTS: The present study focused on the nature of fibrocellular tissue in humans by use of immunocytochemical techniques. Four hearts (five coronary arteries) were investigated; time lapse between PTCA and death varied between 20 days (two arteries) and 1 year 7 months. Proliferating cells stained positive with smooth muscle cell-specific monoclonal antibodies. Cells from early proliferative lesions (20 days) have a phenotypic expression different from cells in "old" lesions. Proliferating cells stained positive with vimentin but were negative with desmin, irrespective of the lesion's age. CONCLUSIONS: The findings indicate a change in actin isoform expression of smooth muscle cells while adapting to a pathological state.

Actins↗
PubMed1991

The early phenomena of restenosis following percutaneous transluminal coronary angioplasty.

In man the early onset of fibrocellular tissue reaction, which leads to restenosis following an initial successful percutaneous transluminal coronary angioplasty, has been poorly documented because of limited opportunities to study this phenomenon. The present study focused on early changes in seven patients who died within 20 days of a percutaneous transluminal coronary angioplasty procedure. Differences in the mode of laceration were noted between concentric and eccentric plaques. In the former, tears occur at the thinnest site of the plaque or within an already attenuated fibrous cap. The injury usually remains limited to the plaque. In eccentric lesions lacerations tend to occur in the non-atherosclerotic wall segment, affecting the musculoelastic layers and the media. A further site of predilection is the border zone between the non-affected wall and the plaque. Early tissue response is characterized by fibrin-platelet depositions, and a proliferation of macrophages and spindle-shaped cells. The latter express the immunocytochemical characteristics of smooth muscle cells. However, differences occur according to the type of tissue injured. Laceration of the musculoelastic layers or media causes a rapid and extensive cellular response. Injury to an atheroma, on the other hand, mainly causes plaque fissures with either mural thrombosis and total luminal obstruction, extensive plaque haemorrhage or a 'wash-out' of the atheromatous debris. In the latter case the lining of the 'crater' shows an accumulation of macrophages and, once more, a proliferation of spindle-shaped cells. The present observations support the concept that the early response is due to an interaction of platelet-fibrin thrombus and smooth muscle cells, with a possible role for macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Morphology of pulmonary atresia with intact ventricular septum in patients dying after operation.

In 1976, we adopted staged surgical management of pulmonary atresia with intact ventricular septum: stage 1 = establishment of a systemic to pulmonary artery shunt; stage 2 = open reconstruction of the right ventricular outflow tract and pulmonary valve; and stage 3 = closure of the shunt and interatrial communication. The morphological features of nine specimens obtained from 10 patients who died were reviewed. Special attention was given to features that might have influenced the poor surgical outcome in these patients. Survival after stage 1 depends on adequate systemic to pulmonary artery blood flow, initially as a combination of ductus arteriosus and shunt flow, with subsequent modification if the ductus closes. After stage 2, survival is influenced by left ventricular function and mitral valve function. The success of final correction (stage 3) depends largely on the morphology of both ventricles and their atrioventricular valves. It appears that the behavior of the ductus arteriosus and the size of the shunt are of vital importance for the survival of the infant. In 3 of the specimens, no right ventricular outflow tract was present, and in 2 others, short chordal attachments of the mitral valve were observed. Staged surgical correction appears to be a satisfactory approach if these considerations are taken into account.

Aorta, Thoracic↗