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Transoesophageal echocardiography has become a widely used diagnostic imaging technique by virtue of its ability to yield high quality images of the heart and great vessels. This thesis is based on work performed between January 1991 and July 1992 during which novel applications of transoesophageal echocardiography were investigated in the intraoperative and critical care settings. The mechanism by which closed chest cardiopulmonary resuscitation (CPR) generates forward blood flow has long been debated. Use of transoesophageal echocardiography allowed the physiology of CPR to be elucidated in 18 human subjects with cardiac arrest. These observations supported the cardiac pump theory of CPR and suggested that transoesophageal echocardiography might be utilised to monitor the efficacy of CPR. A preliminary investigation of CPR performed with the active compression-decompression device is described. The pathophysiology of the fat embolism syndrome (FES) is poorly understood. Transoesophageal echocardiography detected intraoperative fat embolism in 24 patients with traumatic injuries, three of whom subsequently developed clinical evidence of FES. Paradoxical embolism through a patent foramen ovale occurred in one subject with fulminating fat embolism. These results support the mechanical theory of the aetiology of fat emboli, and suggest that transoesophageal echocardiography might be used to identify patients at greatest risk of FES. The role of transoesophageal echocardiography in monitoring regional and global myocardial function was explored in a study of the cardioprotective properties of acadesine in patients undergoing coronary artery bypass surgery. No differences were observed between the acadesine and control groups in the incidence of new regional wall motion abnormalities or in changes in the areas ejection fraction. The strengths and limitations of transoesophageal echocardiography are discussed.

Provision of extra glutamine to the post-operative patient as the dipeptide L-Alanyl-L-Glutamine (Ala-Gln) results in improved whole body nitrogen balance. In the present studies the acute effects and the possible mechanisms of action of this dipeptide on muscle protein balance have been studied in 15 healthy post-absorptive subjects and in 16 intensive care unit patients who had undergone major elective abdominal surgery. Whole body and skeletal muscle protein turnover were investigated using primed, constant infusions of the stable isotope tracers L-[1-<SUP>13</SUP>C]leucine and L-[<SUP>15</SUP>N]phenylalanine, with determination of plasma leucine-C flux and <SUP>13</SUP>CO<SUB>2</SUB> production, assay of L-[1-<SUP>13</SUP>C]leucine incorporation into mixed anterior tibial muscle protein sampled by biopsy and arteriovenous forearm exchange of L-[<SUP>15</SUP>N]phenylalanine with net release of 3-methylhistidine from forearm tissues to assess muscle mixed protein turnover and myofibrillar protein breakdown respectively. Parenteral administration of the dipeptide Ala-Gln increased plasma and intramuscular glutamine concentrations in healthy subjects and in post-operative patients. In healthy postabsorptive subjects, mixed muscle protein synthesis was increased with no significant effect on mixed muscle protein breakdown or on whole-body protein turnover, although small reductions were observed in whole-body flux of leucine and phenylalanine. The increased glutamine availability in muscle <I>per se</I> appeared to stimulate muscle protein synthesis, calculated on the basis of the enrichments of plasma α-ketoisocaproate. Since Ala-Gln infusion does not appear to alter whole-body protein turnover it is likely that in the absence of availability of dietary amino acids, skeletal muscle protein synthesis is increased by glutamine at the expense of non-muscle protein, as the muscle free amino acid pool could not sustain such an increase for more than a few minutes.

Autologous bone marrow transplantation is used successfully as intensive therapy for patients with haematological malignancies and other solid tumours. Peripheral blood contains haematopoietic progenitors whose levels are greatly increased during very early remission after treatment for acute leukaemia or after high dose chemotherapy schedules. These circulating progenitors have been harvested by leucapheresis and used as an alternative to bone marrow as salvage after myeloablative treatments. Peripheral blood stem cells (PBSC) appear to have several advantages over bone marrow including rapid haematopoietic reconstitution after transplantation, the ability to collect PBSC without a general anaesthetic and in the presence of bone marrow abnormalities and the possibility of minimal tumour contamination. My aims were 1) to establish the response of PBSC, measured by the CFU-GM assay, to standard chemotherapy regimes with particular reference to patients with lymphoma, 2) to assess our ability to harvest these progenitors by leukapheresis when numbers were raised and 3) to determine tumour infiltration in PBSC harvests using Southern blotting techniques. Circulating CFU-GM were studied sequentially in 64 patients (40 female, 24 male) 24 non-Hodgkin's lymphoma (NHL), 22 Hodgkin's disease (HD), 9 acute myeloid leukaemia (AML), 5 acute lymphoblastic leukaemia (ALL) and 4 myeloma. Three patients with NHL receiving ALL type therapy showed a mean increase in CFU-GM 15.6 fold over normal values occurring on day 21. Eighteen received CHOP based regimes and demonstrated a 6.2 fold rise between days 15-28. PEEC increased progenitors 43 fold, however CVP and VAD only raised CFU-GM by 2.9 and 2.4 fold respectively. In those patients wth HD a 14.5 fold increase in PBSC was induced in the 4 patients treated with HOPE-bleo. ABVD and MOPP raised peak values to 2.8 and 3.5 times normal and ChlVPP produced a 2.9 fold increase. In the lymphoma group as a whole, standard chemotherapy failed to mobilise PBSC in 15% of patients. Significantly lower peak CFU-GM were found in those who had received previous chemotherapy or who had marrow involvement with disease.

This thesis has outlined the development of operations for duodenal ulcer from gastro-enterostomy which sought initially to merely bypass the ulcer, to an increasing physiological approach which progressively sought to reduce gastric secretion whilst minimising operative sequelae. The published results for gastro-enterostomy alone, Polya gastrectomy, truncal vagotomy with gastro-enterostomy and with pyloroplasty and finally for highly selective vagotomy have been critically reviewed. Dissatisfaction with operative mortality and recurrent ulcer as the sole criteria of success led to the development of methods to assess quality of life. The application of computer technology has permitted analysis of quality of life over some 20 years after five principal operations for duodenal ulcer at the Western General Hospital, Edinburgh. Paradoxically partial gastrectomy was associated with a superior quality of life than the more commonly used procedures involving truncal vagotomy. Highly selective vagotomy has been shown to be a safe and effective operation for duodenal ulcer which modifies the diathesis so that recurrent ulcer is more amenable to medical therapy. The incidence of duodenal ulcer has been shown to be in continuing decline. The treatment of perforated duodenal ulcer by simple closure and H2 receptor antagonists has been shown to have superseded immediate definitive operation for perforated ulcer. Surgical treatment of duodenal ulcer has been shown to be associated with an increased long term mortality predominantly through increased respiratory and circulatory deaths in the first post-operative year. A long term increase in death from malignant disease particularly of bronchus has also been demonstrated.

In the last hundred years, improved social conditions and advances in medical science has rendered previously fatal conditions curable. Modern surgical practice is now too complex to be measured by mortality and morbidity alone. Subjective, patient derived outcome measures are slowly gaining influence in other fields. Health status, or Quality of Life (QoL), measurement has not been widely adopted in surgical practice. To test the hypothesis that <i>Health status measures, scientifically applied, provide important additional information to the surgeon</i>, the techniques were applied to three diverse areas of surgical practice as models for broader application. <i>Chemotherapy for advanced breast cancer patients</i> Chemotherapy has little effect on survival in patients with advanced breast cancer. UICC response and toxicity criteria are used to measure outcome and QoL measurement is a rarity. Using a diary developed to make QoL measurement simpler, a randomised trial was mounted to compare QoL scores in patients receiving two regimens of differing toxicity. <i>Psychological screening for Non Specific Abdominal Pain</i> Patients with Non Specific Abdominal Pain (NSAP) are significant consumers of surgical resources but a psychological contributor is often suspected. In a prospective study, 131 patients aged 14-40 admitted with acute abdominal pain were assessed using the General Health-30 (GHQ) and Hospital Anxiety and Depression (HAD) questionnaires, and a structured interview. <i>Health status after minor surgery</i> Fifty seven general surgical patients having day-surgery completed three questionnaires, the NHP the HAD scale and the GHQ before surgery and after 6 months. A success was reported by 78%, improved health by 64% and improved QoL by 69%.

Rheological parameters and levels of plasma fibrinogen, cross-linked fibrin degradation products (FDP's), von Willebrand Factor antigen (vWF), factor VII, and Plasminogen Activator Inhibitor (P.A.I.), were found to be altered in 219 patients with occlusive arterial disease undergoing revascularisation procedures, when compared with an age-matched random population sample. Elevated levels of some of these potential thrombotic mediators are associated with the angiographic severity of arterial disease on univariate analysis, while multivariate analysis indicates that log (FDP) is independently related to disease severity, and other thrombotic mediators show a trend towards significant independent association. Surgical relief of critical limb ischaemia in 82 of these patients returned the alterations in blood rheology to control levels, but plasma fibrinogen, vWF, P.A.I., and FDP levels remained significantly higher than in the population controls. Percutaneous angioplasty in 40 cases was associated with transient alterations in vWF and t.P.A. levels in arterial blood that may be a consequence of endothelial injury, and with a significant elevation in cross-linked FDP levels 3 months after successful angioplasty. This alteration in fibrin turnover may be related to restenosis following angioplasty. Elevated pre-operative plasma fibrinogen, vWF, and FDP's, were associated with graft occlusion and patient death on univariate analysis of 186 consecutive infra-inguinal bypass grafts, while multivariate analysis indicates that pre-operative plasma von Willebrand Factor levels (p < 0.001), systolic ankle pressure (p < 0.01), female sex (p = 0.03), and limb sepsis (p = 0.01), are all independently predictive of graft occlusion and patient death within 1 year following surgery.

The need for an effective means of limiting the development of anastomic neointimal hyperplasia forms the basis of this thesis. Endovascular stents were developed for use in native arteries after balloon angioplasty to overcome vessel elastic recoil as well as to rescue immediate angioplasty failures and intimal dissections. The work presented in this thesis was performed in order to investigate the effect on the site and development of anastomotic neointimal hyperplasia of placing such a device across the distal anastomosis of an animal model of an arterial bypass graft. A canine model of an aorto-bi-iliac bypass graft was developed and two separate distal anastomotic patterns investigated in separate experiments, namely the end-to-end and the end-to-side configurations. The early and late effects of stenting the distal anastomoses were examined for both models. In the following Sections, an overview of anastomotic neointimal hyperplasia is presented. After outlining basic histological and pathophysiological considerations, a review of a variety of operative and pharmacological approaches to anastomotic neointimal hyperplasia that have been described in the literature is presented. There follows a general review of the use of endovascular stents prior to a description of my own experimental work on endovascular anastomotic stenting and the results obtained. These results are then analysed with particular focus on possible future refinements and modifications of the experimental model as well as the clinical applicability of anastomotic stenting. The work presented in this thesis represents a novel approach to the problem of anastomotic neointimal hyperplasia in lower limb arterial bypass grafts.

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No description available.