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Biomedical subjects

S R Large

Publications and source records attributed to S R Large.

At least 73 records · Page 4Linked to original sources
PubMed1992

Impairment of coronary flow reserve in orthotopic cardiac transplant recipients with minor coronary occlusive disease.

OBJECTIVE: Coronary occlusive disease is the major long-term complication after cardiac transplantation. The relation between minor angiographic abnormalities and myocardial perfusion has not been previously assessed in a large number of cardiac transplant patients. DESIGN: Prospective study. Coronary flow reserve was measured with an intracoronary Doppler flow probe in the proximal left anterior descending coronary artery in each patient. A dose of intracoronary papaverine producing maximal vasodilation was then administered. SETTING: A regional cardiothoracic centre and a supraregional transplant unit. PATIENTS: Seven patients with chest pain but normal coronary anatomy (controls), and 61 cardiac transplant patients between three months and 10 years after operation (median 4.5 years). Twenty one cardiac transplant patients had angiographic evidence of minor coronary occlusive disease (mean (SD) percentage stenosis diameter 23% (6%)) in a primary or secondary coronary vessel (group 1), with 12 of these in the left anterior descending coronary artery (stenosis diameter (mean (SD) 24% (8%)). The remaining 40 transplant patients had normal coronary angiograms (group 2). MAIN OUTCOME MEASURE: Coronary flow reserve was defined as the ratio of the peak flow velocity after papaverine to the resting flow velocity. RESULTS: Group 1 patients had a noticeably impaired coronary flow reserve (2.6 (1.1)) compared with control patients (3.9 (0.4), p = 0.05) and, after adjusting for year after operation, compared with group 2 patients (3.8 (1.0), p < 0.001). No other variables were associated with a reduction in coronary flow reserve. Mean resting flow velocity was similar in all three groups (controls, 7.4 (4.6) cm/s; group 1, 7.5 (5.9) cm/s; and group 2, 7.3 (3.9) cm/s). Mean peak flow velocity response to papaverine was reduced in group 1 patients (18.1 (13.5) cm/s) relative to group 2 patients (27.5 (15.4) cm/s, p = 0.05) but not controls (28.4 (15.1) cm/s, p = 0.1). CONCLUSIONS: Coronary flow reserve and the peak flow response to the coronary vascular smooth muscle relaxant papaverine are impaired in cardiac transplant patients with minor coronary occlusive disease. This disturbance of cardiac microvascular function may contribute to the late morbidity and mortality seen in cardiac transplant patients with coronary occlusive disease.

Blood Flow Velocity↗
PubMed1991

Impairment of endothelium-dependent pulmonary-artery relaxation in chronic obstructive lung disease.

BACKGROUND: Endothelial cells release endothelium-derived relaxing factor (EDRF) in a variety of vascular beds, including the pulmonary circulation. However, the role of EDRF-mediated pulmonary-artery relaxation in chronic hypoxic lung disease is unknown. METHODS: We studied endothelium-dependent relaxation mediated by EDRF in vitro in pulmonary arteries that had been obtained from 22 patients undergoing heart-lung transplantation for end-stage chronic obstructive lung disease. Control pulmonary arteries were obtained from 15 patients undergoing lobectomy for lung carcinoma who did not have evidence of other chronic lung disease. The responses of all vascular rings (external diameter, 1.2 to 3.4 mm) to the endothelium-dependent vasodilators acetylcholine and adenosine diphosphate were studied immediately after lung excision. RESULTS: Pulmonary arterial rings from the patients with chronic lung disease developed a greater tension (2.19 +/- 0.16 g) in response to phenylephrine (10(-6) M) than the rings from control patients (1.28 +/- 0.18 g, P less than 0.05). Inhibition of EDRF synthesis by treatment with NG-monomethyl-L-arginine (10(-4) M) eliminated this difference, increasing the tension in the rings from the controls (P less than 0.01) but not in those from the patients with chronic lung disease. Rings from control patients relaxed in response to cumulative doses (10(-10) to 10(-5) M) of acetylcholine (maximal relaxation, 81.3 +/- 3.9 percent) and adenosine diphosphate (maximal relaxation, 85.3 +/- 2.6 percent). By contrast, rings from patients with chronic obstructive lung disease achieved only 41.3 +/- 4.8 percent of maximal relaxation in response to acetylcholine (n = 32) and 49.4 +/- 5.5 percent in response to adenosine diphosphate (n = 24) (P less than 0.001, as compared with control rings). Rings from both the controls and the patients with chronic lung disease relaxed similarly in response to the endothelium-independent vasodilator sodium nitroprusside (10(-4) M). There was an inverse correlation between the degree of intimal thickening and the level of maximal relaxation of the rings from the patients with chronic lung disease (r = -0.60, P less than 0.001). Maximal relaxation was also related directly to the partial pressure of arterial oxygen before transplantation (r = 0.68, P less than 0.01) and inversely to the partial pressure of arterial carbon dioxide before transplantation (r = -0.55, P less than 0.01), but not to the forced expiratory volume in one second (r = 0.19, P not significant). CONCLUSIONS: Endothelium-dependent pulmonary-artery relaxation in vitro is impaired in arteries from patients with end-stage chronic obstructive lung disease. Such impairment may contribute to the development of pulmonary hypertension in chronic hypoxic lung disease.

Acetylcholine↗
PubMed1991

Experience of percutaneous transluminal coronary angioplasty in orthotopic cardiac transplant recipients.

We evaluated the role of percutaneous transluminal coronary angioplasty (PTCA) in a series of orthotopic cardiac transplant recipients with severe epicardial coronary occlusive disease. Ten orthotopic cardiac transplant patients treated by PTCA up to March 1990 were reviewed. All had significant epicardial coronary artery lesions (greater than 70% stenosis compared with the adjacent healthy artery) and exercise electrocardiogram or isotope perfusion evidence of myocardial ischaemia in the relevant region. Primary angiographic PTCA success was achieved in 12 of the 16 lesions attempted (75%). Mean stenosis improvement was from 80% of adjacent healthy artery (range 70-90%) to 12% (range 0-20%). Median angiographic follow-up of 9 months (2-25 months) is available for all patients. The mean recurrence rate is 33% (4 of 12 successfully treated lesions) defined as greater than 50% reduction in the original gain at the PTCA. We have shown that PTCA is technically possible in a series of cardiac transplant recipients. The primary success and recurrence rates are comparable to the use of PTCA in conventional atherosclerotic coronary disease.

Adult↗
PubMed1991

Risk factor analysis for the major hazards following heart transplantation--rejection, infection, and coronary occlusive disease.

This study demonstrates the importance of analyzing survival by cause of death in order to achieve a better understanding of the prognostic indicators involved. It further emphasizes the need for analysis of risk factors in both univariate and multivariate models, and the danger of making judgements based on premature analysis of data on follow-up after heart transplantation. Survival following transplantation is characterized by the major hazards of early death due to infection and rejection and late graft loss due to coronary occlusive disease (COD). This study summarizes the first-graft survival experience for 323 transplant patients at Papworth Hospital, and assesses a number of potential risk factors for (1) early mortality, (2) late mortality from COD, and (3) development of COD. The potential risk factors considered for all hazards are donor and recipient age, sex, blood group, and matching of these factors; donor cause of death and recipient immunosuppression; inotropic support; waiting time; preoperative diagnosis and previous cardiac surgery; ischemic time; and extubation time. In addition, for development of, and graft loss from, COD, perioperative rejection and cytomegalovirus infection; hypertension at discharge; and cholesterol, triglycerides, and lipids at two years were assessed as risk factors. Advances in immunosuppression were observed to have increased overall survival rates and decreased mortality from infection, rejection, and COD, as well as decreasing morbidity from COD. Fatal rejection was found to be more likely in female recipients, recipients over 40 years, recipients of grafts from donors over 30 years old, patients who were transplanted for valvular heart disease, and patients who waited less than three months for their transplant. Male recipients of female donor organs were more likely to lose their grafts as a result of COD. Patients older than 50 and hearts from donors older than 40 conferred a high risk of development of and loss from COD. Patients transplanted for ischemic heart disease were more likely to develop COD. High cholesterol, low HDL, high LDL, and high triglycerides at two years after transplant showed some evidence of high risk for the subsequent development of COD, although these relationships are not statistically significant at this stage. Contrary to other recent studies, cytomegalovirus infection was not found to be a risk factor for the development of COD.

Adolescent↗
PubMed1991

Diagnosis of early cardiac transplant rejection by fall in evoked T wave amplitude measured using an externalized QT driven rate responsive pacemaker.

Reliable diagnosis of cardiac allograft rejection is at present only possible using endomyocardial biopsy. We have serially measured epicardial evoked T wave amplitude during ventricular pacing with an externalized QT driven rate responsive pacemaker telemetered to a TP2 analyzer in 13 patients (12 males) followed for 19 (14-26) days after transplantation. A total of 228 records were analyzed. Rejection was defined on endomyocardial biopsy. On 17 of the 31 occasions on which biopsy was performed during the study, specimens showed significant (moderate) rejection. In 11 patients the initial biopsy proven rejection episode was associated with a significant fall in the evoked T wave amplitude from 1.3 (0.7-2.3) mV to 0.6 (0.5-1.8) mV (P less than 0.005), which began 2 (1-4) days earlier. One patient with uncontrolled diabetes mellitus had no change in evoked T wave amplitude during rejection. The evoked T wave amplitude did not fall in the absence of histologic rejection. These results suggest a noninvasive method for detecting cardiac rejection, which appears both sensitive (92%) and specific (100%) in the first rejection episodes.

Adult↗
PubMed1989

Heart and heart-lung transplantation, Papworth Hospital, 1979-1989.

The quality of life for those who survive the first 3 months after transplantation is generally good (10). The duration of hospital stay and the cost of transplantation per patient has been reduced during the last 3 years. Cardiologists are coming to appreciate the therapeutic potential of both heart and heart-lung transplantation. One of the chief logistical problems now being faced is that of increasing the provision of transplant services to match the increasing demand. It was said in an earlier edition of this book that this would be donor organ limited and that pattern already seen in the United States is becoming apparent in the United Kingdom. The broad principles of management of heart and heart-lung recipients have been established. Further improvements in medium and long-term results can be anticipated as a result of refining immunosuppression and defining the cause of chronic donor organ related damage (small vessel coronary occlusive disease in heart transplants and chronic obliterative bronchiolitis in heart-lung transplants). Heart transplantation has become firmly established as a therapeutic option for life threatening heart disease. It is probably too early to attribute this label to heart-lung transplantation which continues through its developmental phase with acceptable short-term results. Improvements in chronic damage characteristic of long-term survival in both heart and heart-lung transplant recipients will be a significant clinical step forward in this field.

Adolescent↗
PubMed1988

Blunt traumatic rupture of the thoracic oesophagus.

A man with a crush injury of his upper abdomen developed bilateral pulmonary empyema after repair of tears of the oesophagus and liver. Attempts to withdraw chest drains led to recurrent septicaemia, treated by reinsertion of the drains plus administration of antibiotics. The communication of the empyema space with both the bronchial tree and the oesophagus was managed successfully with intermittent positive pressure ventilation and with a double lumen endobronchial tube isolating the right lung for 10 days. Traumatic rupture of the thoracic oesophagus carries a high mortality and prompt repair is vital.

Adult↗
PubMed1986

Surgical pathology of the thymus: 20 years' experience.

Fifty five patients underwent thymic surgery at Papworth Hospital from April 1964 to March 1984. The number presenting and the percentage with symptoms annually remained unchanged during this period. Forty four of these 55 patients had tumours. Twenty eight had thymomas (18% of whom had myasthenia gravis and 7% red cell aplasia), nine Hodgkin's disease, four germ cell tumours, and three secondary carcinomatous tumours. Five tumours were cystic. Six further patients had non-tumourous cystic lesions (four simple, one foregut, one lymphangiectatic). The remaining five patients had follicular hyperplasia; all of these had myasthenia gravis. Complete excision was performed in 41 of the 55 patients. So far survival is 100% in those with benign lesions other than benign thymomas, where the survival was 70% at five years. Those with malignant thymomas had a 60% survival rate at five years and those with Hodgkin's disease 29%.

Adolescent↗
PubMed1985

Incidence and aetiology of a raised hemidiaphragm after cardiopulmonary bypass.

A raised hemidiaphragm has been reported as an uncommon complication of cardiopulmonary bypass, possibly resulting from cold injury to the phrenic nerve. At Papworth Hospital myocardial protection during cardiac arrest relies in part on irrigation of the pericardial cavity with large volumes of Hartmann's solution at 4 degrees C. Retrospective review of the chest radiographs of 100 consecutive patients undergoing cardiopulmonary bypass showed that 31 had a raised left hemidiaphragm soon after operation. The only significant correlation was with aortic cross clamp time (p less than 0.03). A prospective study of 36 consecutive patients undergoing cardiopulmonary bypass was then undertaken with diaphragmatic screening and chest radiography. Preoperative screening gave normal results in all patients. In the early postoperative period 16 (44%) had left diaphragmatic weakness or paralysis, two (5.5%) right sided weakness, and two (5.5%) bilateral weakness. Repeat screening of these patients showed resolution in all but four cases (80%) at six months and in all but two (90%) at one year. The greater number of left sided lesions than of right (8:1) is probably due to the fact that the cold jet of irrigating fluid is directed towards the left phrenic nerve. These findings have implications with regard to the optimum temperature of the irrigant fluid for myocardial protection during cardiopulmonary bypass.

Adolescent↗