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Biomedical subjects

A E Farnsworth

Publications and source records attributed to A E Farnsworth.

At least 19 recordsLinked to original sources
PubMed2001

Immunohistochemical and ultrastructural evidence that dendritic cells infiltrate stenotic aortocoronary saphenous vein bypass grafts.

We earlier speculated that antigen-presenting dendritic cells may be involved in the immune reactions leading to saphenous vein bypass graft failure. The purpose of this study was to confirm whether dendritic cells are present in stenotic human saphenous vein bypass grafts. Segments of stenotic saphenous vein grafts were explanted from 14 patients at re-do bypass operation and ten normal saphenous veins were harvested during femoro-popliteal grafting. Sections of specimens were analysed using cell type specific antibodies to identify dendritic cells (CD1a, S-100), T-lymphocytes (CD3), macrophages (CD68), smooth muscle cells (alpha-SMA) and endothelial cells (FVIII). Dual immunostaining, confocal immunofluorescent laser scanning microscopy and electron microscopy were used. Stenotic grafts showed structural alterations of intimal hyperplasia and varying degrees of atherosclerotic degeneration. No cells expressing CD1a and S-100 were observed in the intima and media of normal saphenous veins. Cells expressing these antigens were present around areas of medial neovascularization and within intimal atherosclerotic lesions in saphenous vein bypass grafts. Electron microscopy demonstrated the presence of cells containing a well-developed tubulovesicular system which is unique to cells from the dendritic cell family. Double immunohistochemistry and confocal immunofluorescent microscopy revealed the co-localization of T-lymphocytes with dendritic cells. Dendritic cells are present in stenotic saphenous vein bypass grafts. Dendritic cells may be responsible for antigen presentation and modulation of immune reactions in accelerated graft atherosclerosis through their interaction with T-lymphocytes.

Adult↗
PubMed2001

Expression of apoptosis-related proteins and structural features of cell death in explanted aortocoronary saphenous vein bypass grafts.

This study aimed to investigate the features of cell death occurring in aortocoronary saphenous vein bypass grafts. Human aortocoronary saphenous vein bypass grafts with angiographic luminal stenosis of > 75% were explanted from 14 patients at redo coronary artery bypass grafting. Proteins associated with apoptotic pathways were identified immunohistochemically using antibodies to Bcl-2, Fas, BAX, p53 and CPP32. Cells undergoing DNA fragmentation were identified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). DNA synthesis was investigated using the antibody to proliferating cell nuclear antigen (PCNA). Ultrastructural features of cell death were examined by electron microscopy. Anti-apoptotic (Bcl-2) and pro-apoptotic (Bax, p53, CPP32 and Fas) proteins were expressed throughout the graft wall, but marked differences in the characteristics of cell death were noted between atherosclerotic and non-atherosclerotic areas of the intima. In atherosclerotic areas, pro-apoptotic proteins were widely expressed, but ultrastructural analysis failed to identify cells showing typical features of apoptosis. In these areas, necrotic cells were frequently observed, with negative correlation of Bcl-2 expression with TUNEL. Pro-apoptotic proteins showed no correlation with TUNEL. In contrast, in non-atherosclerotic areas of vein grafts, the expression of both anti-apoptotic (Bcl-2) and pro-apoptotic proteins (p53, Bax and CPP32) correlated with TUNEL. In atherosclerotic areas, non-atherosclerotic intimal areas, and in the underlying media, the numbers of TUNEL+ cells correlated with PCNA positivity. Ultrastructurally, apoptotic bodies and features of necrosis were observed in non-atherosclerotic areas of grafts. The present observations indicate that in atherosclerotic areas, cell death occurs mainly by necrosis, while in non-atherosclerotic areas, cell death occurs by both necrosis and apoptosis. An imbalance between DNA fragmentation and DNA synthesis may contribute to graft instability and failure.

Aged↗
PubMed2001

Expression of vascular endothelial growth factor in aortocoronary saphenous vein bypass grafts.

Neovascularisation is a prominent feature of long-term aortocoronary saphenous vein bypass grafts but mechanisms involved in the formation of neovessels have not been previously studied. Vascular Endothelial Growth Factor (VEGF) is an important angiogenic factor that induces migration and proliferation of endothelial cells, enhances permeability and modulates thrombogenecity. This study investigated the expression of VEGF in aortocoronary saphenous vein bypass grafts. Aortocoronary saphenous vein bypass grafts with angiographic luminal stenosis of >75% were explanted from 14 patients at redo coronary artery bypass grafting. The grafts demonstrated two distinct forms of graft occlusion: four out of the 14 graft occlusions (29%) resulted from severe hyperplastic transformation of the intima complicated by thrombi attached to the degenerating liminal endothelium; the remaining graft occlusions (71%) were due to the development of atherosclerotic lesions associated with mural thrombosis. Hiperplastically altered intimal segments were practically free of neovascularisation while atherosclerotic-like lesions contained neovessels irregularly distributed throughout. Intimal neovessels were located exclusively in microzones enriched with VEGF-expressing cells and, furthermore, neovascular endothelial cells themselves also displayed VEGF immunopositivity. Double-immunostaining revealed that in areas of neovascularisation, the vast majority macrophages (CD68+) expressed VEGF. Some CD68+ foam cells that surrounded branches of neovascularisation were also VEGF-positive. These findings suggest that VEGF expressed by neovascular endothelial cells and by macrophages may act as a local regulator of endothelial cells functions and may induce intimal neovascularisation in aortocoronary saphenous vein bypass grafts affected by atherosclerosis.

Aged↗
PubMed2000

Dendritic cells in aortocoronary saphenous vein bypass grafts.

Dendritic cells are specialised leucocytes responsible for capturing and presenting antigens to T lymphocytes, which in turn mediate immune responses in various pathological conditions. The observations in this study demonstrate that dendritic cells are present in stenotic aortocoronary saphenous vein bypass grafts, which suggest that these cells may be involved in inflammatory actions which may subsequently contribute to graft failure.

Journal Article↗
PubMed2000

Electron-microscopic detection of apoptotic and necrotic cell death in non-atherosclerotic areas of stenotic aortocoronary saphenous vein bypass grafts.

Aortocoronary saphenous vein bypass grafts undergo structural alterations within the arterialized vein, resulting in graft stenosis and failure. Areas of the acellular intima contribute to fissuring, cracking and ulceration, while areas of the media become highly vascular but thinned. This study aimed to examine the ultrastructural features of cell death, including apoptosis and necrosis, in non-atherosclerotic areas of the stenotic aortocoronary saphenous vein bypass grafts. Thirteen stenotic vein grafts were obtained at redo coronary artery bypass grafting. The ultrastructural features of cell death were analysed by electron microscopy. Typical features of necrosis, including focal areas of cytoplasmic oedema, plasmalemmal destruction and nuclear condensation with cytoplasmic organelle destruction, were observed throughout the intima and media. Features of apoptosis, including the presence of apoptotic bodies, were also identified in the hyperplastic intima and its adjacent media. Our observations suggest that both apoptosis and necrosis occur in non-atherosclerotic areas of stenotic aortocoronary saphenous vein bypass grafts.

Aged↗
PubMed1999

Involvement of dendritic cells in long-term aortocoronary saphenous vein bypass graft failure.

Antigen-presenting dendritic cells are present in atherosclerotic lesions in human arterial intima, but have not been investigated in atherosclerotic and hyperplastic stenotic lesions that affect vein grafts used as arterial conduits. This study was undertaken to examine whether dendritic cells are present in aortocoronary artery saphenous vein bypass grafts affected by high-grade atheromatous stenosis. Stenotic saphenous vein coronary artery bypass grafts (angiographic luminal stenosis > 75%) were harvested from 10 patients (nine male, one female), aged 4271 years (mean 56.5) at re-do operation. The mean time interval from bypass surgery to the excision of stenotic grafts was 11.5 years (range 2-21). The specimens were fixed in 10% buffered formalin, embedded in paraffin blocks and the sections stained with antibodies to S-100 (to identify dendritic cells), CD3 (T cells), CD68 (macrophages), von Willebrand factor (endothelial cells) and alpha-smooth muscle actin (smooth muscle cells) using avidin-biotin complex immunoperoxidase technique. Normal veins were obtained during saphenous vein femoro-popliteal grafting. The stenotic venous grafts showed histological features typical of extensive arterialization, intimal hyperplasia, atherosclerotic plaque-like lesions, calcification and thrombosis. In areas of intimal hyperplasia, S-10O-positive cells were distributed irregularly among smooth muscle cells. S-100-positive dendritic cells were seen most frequently within atherosclerotic plaque-like lesions where they co-localized with CD3+ cells and CD68+ cells. S-100-positive dendritic cells were also seen accumulating within calcific foci. No S-100-positve cells were found in normal, ungrafted saphenous veins. We conclude that dendritic cells are present in aortocoronary saphenous vein bypass grafts affected by high grade stenosis. Dendritic cells are probably involved in immune mechanisms of atherogenesis through their interactions with T cells and macrophages. The accumulation of dendritic cells within calcific foci suggests their contribution to the calcification of stenotic venous grafts.

Adult↗
PubMed1999

Structural features of cell death in atherosclerotic lesions affecting long-term aortocoronary saphenous vein bypass grafts.

Aortocoronary saphenous vein bypass grafts fail because of structural pathologies (thrombosis, intimal hyperplasia and atherosclerosis) within the 'arterialized' vein leading to graft stenosis. This study examined structural characteristics of atherosclerotic alterations in long-term aortocoronary artery saphenous vein bypass grafts with particular attention to the features of cell death in atherosclerotic lesions. Stenotic vein grafts were obtained from 10 patients at redo coronary artery bypass grafting operations. All the grafts were affected by histological abnormalities, with eight out of ten grafts showing evidence of atherosclerotic alterations in the intimal hyperplastic layer. Areas containing foam cells were examined by electron microscopy. Cells with cytoplasmic lipid accumulations were characterized by varying degrees of chromatin condensation, fragmentation or dispersion, by focal areas of oedema and vacuolisation of their cytoplasm, and by plasmalemmal destruction. Some lipid-filled cells exhibiting signs of destruction contained myofilaments and basal membrane fragments, allowing them to be identified as smooth muscle cells. Macrophage foam cells were found to have undergone similar destruction. No cells showing nuclear degeneration were observed to have intact cytoplasmic organelles. Neither were apoptotic bodies identified, but necrotic remnants were frequently seen. The results suggest that cell death in atherosclerotic lesions affecting aortocoronary artery saphenous vein bypass grafts occurs through oncosis rather than by apoptosis.

Adult↗
PubMed1998

Left atrial reduction for chronic atrial fibrillation associated with mitral valve disease.

Currently available surgical procedures to control chronic atrial fibrillation associated with mitral valvar disease are not always successful. The size of the left atrium is a major factor in the initiation and maintenance of atrial fibrillation. Here we describe a case of ablation of atrial fibrillation with left atrial reduction and pulmonary vein isolation in a patient with mitral valve disease.

Aged↗
PubMed1993

Homograft aortic root replacement for destructive prosthetic endocarditis.

Prosthetic aortic valve endocarditis with extensive destruction of the aortic root, annular abscess formation, and left ventriculoaortic discontinuity was seen in 3 patients, with aorta to left atrial fistula formation in 2. Homograft aortic root replacement with use of the anterior mitral leaflet of the aortic root to repair the fistula was used successfully in all 3 patients. Their case reports are discussed to highlight the use of the homograft aortic root in these complicated cases, and to report the occurrence of aorto-left atrial fistula in prosthetic valve endocarditis.

Adult↗
PubMed1989

Repeat myocardial revascularization surgery: an analysis of 169 cases.

One hundred and sixty-nine patients who underwent repeated myocardial revascularization surgery between 1982 and 1987 were studied. The mean interval between operations was 91.6 +/- 7.3 months. The indications for repeated surgery were graft failure in 37.2% of patients, progressive coronary atherosclerosis in 40.2% of patients and a combination of the two causes in 22.5% of patients. The mean number of grafts that were inserted was 2.74 +/- 0.61 grafts per patient at the second operation. Coronary endarterectomy as an adjunctive procedure was necessary in 17.1% of patients. The hospital mortality rate was 4.1%, with a 1.8% incidence of perioperative myocardial infarctions. Of the surviving patients, 96.3% were available for follow-up at a mean of 19 +/- 6.4 months. Of these patients, 68.5% were well and could be categorized into the New York Heart Association's functional class I. We conclude that both progression of coronary atherosclerosis in native vessels and obstruction of venous grafts cause recurrent angina and that repeated myocardial revascularization surgery is a feasible treatment option in these patients.

Adult↗
PubMed1989

Homograft aortic root replacement to correct infective endocarditis requiring seven open cardiac procedures.

Infective endocarditis, presumably from a septic dental focus, affecting the aortic valve was seen as acute aortic regurgitation in a 20-year-old woman. Seven open cardiac procedures for replacement of the aortic valve and left ventricular outflow tract were performed over the subsequent 6 years. Aortic root replacement using a fresh antibiotic-sterilized homograft was performed as the last definitive operative procedure. This article is presented to highlight (1) the use of homograft aortic root replacement for extensive involvement of aortic valve and left ventricular outflow tract in cases of infective endocarditis and (2) the feasibility of multiple sternal reentries when indicated.

Adult↗
PubMed1989

Ascending aortic aneurysms associated with aortic valve regurgitation: St Vincent's Hospital's experience.

This report represents a retrospective analysis of the St Vincent's Hospital experience with combined replacement of the aortic valve and ascending aorta using a composite conduit and coronary artery reimplantation, in 44 patients, from 1 January 1981 to 30 June 1988. The mean age at operation was 48 years. Annuloaortic ectasia was the most common indication for operation in 24 patients (54%). There were three hospital deaths (7%). Forty-one patients were discharged from hospital and were followed up for a total of 1,106 patient months (mean = 26.5 months). There were three late deaths (7%). One death was due to a new dissection, one to a cerebrovascular accident and one to a drug overdose. So far, no patients have required reoperation. Of the 36 surviving patients available for follow-up, 28 are in New York Heart Association class I, seven patients are in class II and one in class III. Composite graft replacement reduces the risk of recurrent dissection and aneurysm formation and of periprosthetic leak. In the present experience, it is the method of choice in patients with degenerative lesions in the ascending aorta and aortic valve and particularly for annuloaortic ectasia. The exact surgical technique currently used has been the result of an evolution of different techniques.

Adolescent↗
PubMed1989

Open cardiac compression in the postoperative cardiac intensive care unit.

Thirty-nine patients required heroic resuscitative measures for sudden hypotension and cardiac arrest in the first 72 hours following cardiac surgery between January 1, 1984 and May 31, 1988. Emergency sternotomy with open cardiac compression was performed in twenty-four of these patients when external cardiac compression failed. These were categorised as Group A. Group B comprised the fifteen patients in whom resuscitation was entirely by means of external compression and adjuvant measures. Survival with NYHA Functional Class I and II status was noted in 75% of patients in Group A, compared with 20% in Group B (P less than 0.002). Emergency sternotomy with open cardiac compression is an effective way of resuscitating patients in the intensive care unit in the first few days following open heart surgery.

Cardiac Surgical Procedures↗
PubMed1988

Psychological adjustment after cardiac transplantation.

Cardiac transplantation is viable therapeutic alternative for patients with end-stage heart disease, which offers a favourable short- and medium-term prognosis. The survival has improved from 20% of patients who survived at one year after transplantation in the 1960s to the present figures of 80%-85% of patients who are alive at one year, and 50%-70% of patients who are alive at five years, after transplantation. Therefore, it seems timely to focus attention on the psychological well-being of cardiac-transplant recipients. The medical literature is scant in regard to the psychiatric and the psychosocial impact of cardiac transplantation on recipients, and a systematic and prospective study of the psychosocial adaptation of recipients is lacking. Since 1984, we have been studying the emotional impact of cardiac transplantation on recipients and their families. This article presents the results for a group of recipients who have been assessed before transplantation, then followed-up at discharge from hospital and at four, eight and 12 months after transplantation. The study attempted to quantitate the recipients' anxiety, depression, body image and subjective quality of life by way of standardized self-assessment questionnaires. The recipients' satisfaction with relationships or their marital situation also was reported, as were their degree of rehabilitation at 12 months and their attitudes to various aspects of treatment after the transplantation. Before the transplantation, 53% of patients reported an increase in anxiety and 34% of patients recorded scores that indicated mild-to-moderate levels of depression. Thirty-seven per cent of patients showed a deterioration in the quality of their lives and 34% of patients had a negative body image. After the transplantation, significant improvements occurred in all parameters, which were maintained at follow-up.

Adaptation, Psychological↗