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Biomedical subjects

J J Dunning

Publications and source records attributed to J J Dunning.

At least 19 recordsLinked to original sources
PubMed2001

Effect of surgical training on outcome and hospital costs in coronary surgery.

BACKGROUND: There is a perceived conflict between the need for service provision and surgical training within the National Health Service (NHS). Trainee surgeons tend to be slower (thereby reducing theatre throughput), and may have more complications (increasing hospital stay and costs). OBJECTIVE: To quantify the effect of training on outcome and costs. DESIGN: Data on 2740 consecutive isolated coronary artery bypass (CABG) operations were analysed retrospectively. Redo and emergency procedures were excluded. The seniority of the operating surgeon was related to operating times, risk stratified outcome, and overall hospital costs. SETTING: Regional cardiothoracic surgery unit. MAIN OUTCOME MEASURES: Postoperative mortality; hospital costs. RESULTS: Consultants, senior trainees, intermediate trainees, and junior trainees performed 1524, 759, 434, and 23 procedures, respectively. Trainees at the three different levels were directly supervised by a consultant in 55%, 95%, and 100% of cases. The unadjusted mortalities were 3.2%, 2.0%, 2.3%, and 4.3%, respectively (NS). There were no significant differences between the groups with respect to time in the intensive care unit and length of hospital stay. The mean cost per patient was pound6619, pound6572, pound6494, and pound6404 (NS). CONCLUSIONS: Trainees performed 44.4% of all CABG operations. There was no detrimental effect on patient outcome, length of hospital stay, or overall hospital costs. There need be little conflict between service and training needs, even in hospitals with extensive training programmes.

Clinical Competence↗
PubMed2000

Life supporting function for over one month of a transgenic porcine heart in a baboon.

BACKGROUND: Inhibition of hyperacute rejection (HAR) and sustained graft survival have been demonstrated in a pig-to-primate model of heterotopic cardiac xenotransplantation using pigs transgenic for human Decay Accelerating Factor (hDAF). Building on this work, an orthotopic model has been developed. This case records 39-day cardiac xenograft function in a life-supporting capacity with clinically applicable immunosuppression. METHODS: Using a heart from an hDAF transgenic pig, an orthotopic cardiac transplant was performed on an adult baboon. The immunosuppressive regimen consisted of induction with a short course of cyclophosphamide, followed by maintenance therapy with cyclosporine A, mycophenolate mofetil and a tapering course of corticosteroids. Post-operative monitoring included daily anti-pig hemolytic antibody titer surveillance and endomyocardial biopsy. RESULTS: The animal survived 39 days and was active and energetic throughout its postoperative course, remaining free of signs of cardiopulmonary failure. Endomyocardial biopsy performed on post-operative Day 36 revealed only patches of sub-endocardial fibrosis with no signs of active rejection. The baboon succumbed to an acute cardiopulmonary decompensation immediately following administration of medication via oral gavage. Post-mortem histopathology demonstrated well-preserved myocardial architecture with small foci of mild humoral rejection. CONCLUSIONS: This case documents the longest survival recorded to date of a discordant orthotopic cardiac xenograft and illustrates that the hDAF transgene combined with a clinically acceptable maintenance immunosuppressive regimen enables sustained, life-supporting function of porcine cardiac xenografts in non-human primates. The inhibition of hyperacute rejection and the subsequent control of humoral and cellular rejection for over 1 month demonstrated in this experiment represent significant progress in the development of a viable strategy for clinical xenotransplantation.

Animals↗
PubMed1999

[Xenotransplantation of hDAF-transgenic swine hearts].

Hearts of transgenic pigs expressing a human regulator of complement activation, decay accelerating factor (hDAF), were transplanted either heterotopically into the abdomen of cynomolgus monkeys or orthotopically into baboons. None of these transgenic hearts was hyperacutely rejected. Immunosuppression with a combination of cyclosporine A, cyclophosphamide and steroids produced a maximum survival of 62 days (median 40 days) in the heterotopic model. Transgenic hearts transplanted into the orthotopic position allowed a maximum survival of 9 days (median 2.5 days). A more effective and less toxic immunosuppressive protocol for the prevention of accelerated xenograft rejection is the subject of ongoing research. The use of organs from transgenic pigs may help to solve the problem of donor shortage in clinical allotransplantation.

Animals↗
PubMed1998

Orthotopic heart transplantation in a transgenic pig-to-primate model.

BACKGROUND: Previous studies demonstrated that hearts from transgenic pigs expressing human decay-accelerating factor (hDAF) were not hyperacutely rejected when transplanted heterotopically into the abdomen of cynomolgus monkeys. This study examines orthotopic transplantation of hDAF transgenic pig hearts into baboon recipients. METHODS: Orthotopic xenogeneic heart transplantation was performed using piglets, transgenic for hDAF, as donors. Ten baboons were used as recipients and were immunosuppressed with a combination of cyclophosphamide, cyclosporine, and steroids. RESULTS: Five grafts failed within 18 hr without any histological signs of hyperacute rejection. Pulmonary artery thrombosis induced by a size mismatch was observed in two of these animals. The other three recipients died because of failure to produce even a low cardiac output and/or dysrhythmia. The remaining five animals survived between four and nine days. One animal died of bronchopneumonia on day 4. Three xenografts stopped beating on day 5 due to acute vascular rejection. The longest survivor was killed on day 9 with a beating, histologically normal xenograft, because of pancytopenia. CONCLUSIONS: The results reported here demonstrate that hDAF transgenic pig hearts are not hyperacutely rejected when transplanted into baboon recipients. Orthotopically transplanted transgenic pig hearts are capable of maintaining cardiac output in baboons. An optimum immunosuppressive regimen is the subject of ongoing research.

Animals↗
PubMed1997

Hyperacute lung rejection in a pig-to-human transplant model: the role of anti-pig antibody and complement.

BACKGROUND: The physiology of hyperacute rejection of pig lung by human blood and the role of antispecies antibody and complement in this phenomenon have not previously been characterized. METHODS: Human blood was perfused through an ex vivo pig heart-lung preparation. In the treatment groups, blood was either unmodified or modified to deplete alternative pathway complement (heat treatment), anti-pig antibody, or both. Control experiments were performed with unmodified and heat-treated pig blood. Physiologic parameters, organ survival, and immunohistology were the primary outcome measures assessed. RESULTS: Pig lung was consistently damaged by human blood within 45 min (median 20 min), as evidenced by elevated pulmonary vascular resistance and parenchymal injury. Immunohistologic studies of perfused lungs showed prominent deposition of IgM and classical pathway component, C4, and weaker deposition of alternative pathway component, properdin. Heat treatment did not impede the rise in pulmonary vascular resistance or significantly prolong survival. Depletion of anti-pig antibody prolonged survival (median 90 min) and attenuated the rise in pulmonary vascular resistance. Antibody absorption, combined with heat treatment of plasma, prevented the elevation in pulmonary vascular resistance and yielded median graft survival (210 min) similar to pig blood perfusion (approximately 240 min). CONCLUSIONS: These results show that elevated pulmonary vascular resistance and pulmonary parenchymal injury are mediated at least in part by antispecies antibody and heat-sensitive pathways. They are consistent with the hypothesis that complement activation contributes significantly to acute lung damage in the pig-to-human species combination.

Animals↗
PubMed1997

Extrusion of Teflon aortic pledgets from a sternal wound six years after cardiac surgery.

We present a case of a cardiac surgery patient with a persistent low-grade discharge from his sternal wound for over six years. It finally healed when some suture material and Teflon felt pledgets were extruded. These had been used intraoperatively to close the aortic cannulation site. The extrusion of prosthetic material from this site after this length of time has never been described.

Coronary Artery Bypass↗
PubMed1995

Cardiac transplantation: a review.

Cardiac transplantation is currently a highly successful treatment for selected patients with end-stage cardiac failure. The long-term results are limited by the development of coronary artery vasculopathy, infection and malignancy. The activity of transplantation programmes worldwide is severely limited by the availability of donor organs. Further refinements of immunosuppressive agents are likely to result in improved prevention of both acute and chronic rejection. The donor pool is unlikely to be significantly extended as a result of measures to increase donor organ supply. Alternative methods to allograft transplantation need further investigation to increase the number of therapeutic options available for those patients with end-stage heart failure.

Animals↗
PubMed1995

Transmyocardial laser revascularization.

In transmyocardial laser revascularization a series of channels are created between the left ventricular cavity and the myocardium. The operation is usually performed in isolation via a left thoracotomy without cardiopulmonary bypass, but has been done in combination with coronary artery bypass grafting. Angina pectoris with coronary artery anatomy unsuitable for either angioplasty or bypass grafting is currently the most common indication for this procedure.

Angina Pectoris↗
PubMed1994

A comparison of the performance of pig hearts perfused with pig or human blood using an ex-vivo working heart model.

The pathophysiology of xenograft hyperacute rejection is still poorly understood although it is believed to involve complement fixation to vascular endothelium, probably as a result of the presence of naturally occurring anti-species antibodies. Hyperacute rejection of pig hearts by human blood was studied in an ex-vivo working heart model. Cardiac performance and immunological reactions occurring in the perfusing blood were studied. Stroke work performed by pig hearts perfused with human blood and their survival (median 47 min: n = 10) was significantly reduced compared to survival (median 158 min: n = 10) and stroke work performed by pig hearts perfused with pig blood. Decomplementation of human blood resulted in improved performance and duration of the action (median survival > 240 min: n = 10) of hearts. Quantitative differences were seen in complement fixation between the groups. Our data demonstrate the central role of complement in the destruction of pig-to-man xenografts.

Animals↗