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L D Sharples

Publications and source records attributed to L D Sharples.

54 records · Page 3Linked to original sources
PubMed1994

Risk factors for survival following combined heart-lung transplantation. The first 100 patients.

As the numbers of heart and lung transplant recipients have increased it has become possible to identify major risk factors for early (within 3 months) and later (after 3 months) death after this procedure. For 100 patients receiving organs between April 1984 and February 1991, and followed up until February 1992, patient characteristics, operative details, and early morbidity were assessed for their effects on early and later deaths. Recipient age, sex, and preoperative diagnosis did not have a significant effect on early (within 3 months) or later death. Positive cytomegalovirus antibody status of donor or recipient conferred greater risk of death within 90 days (odds ratio [OR] = 3.24, P = 0.06). Greater than 2 L blood in the first 24 hr after operation (OR = 6.00, P = 0.05), and ventilation for greater than 24 hr (OR = 4.87, P = 0.006) were significant prognostic indicators of early death. After the first 3 months, the main risk factor for death was rejection in the first 3 months (OR = 1.38 per episode, P = 0.008). Early infection in general and CMV infection in particular were associated with a small increase in risk. This study confirms the importance of matching donor and recipient for CMV and shows that difficulties during operation, reflected in postoperative bleeding and ventilation times increased the chance of early death. Later death was associated with early acute rejection. A detrimental effect of infection, including CMV infection, either does not exist, or is too small to be detected in a study of this size.

Actuarial Analysis↗
PubMed1994

Donor and recipient predicted lung volume and lung size after heart-lung transplantation.

Lung volumes after heart-lung transplantation (HLT) were recorded and compared with measurements at the time of assessment for surgery and the predicted values for recipients. The influence of donor lung size and recipients' underlying lung disease was evaluated. All patients underwent HLT between April 1984 and April 1991, and only those 82 who survived for at least 6 mo were studied. Mean total lung capacity (TLC) at preoperative assessment was 112% (SD = 28%) of the value predicted for recipients. One month after HLT, mean TLC was 83% (SD = 15%) of the predicted value but increased to 100% (SD = 15%) after 9 mo. No further change in average TLC occurred for 5 yr subsequently. The mean TLC of patients with emphysema before surgery was 164% (SD = 26%) of the predicted value and fell to the predicted value within 1 mo of HLT. The TLC in patients with primary pulmonary hypertension before surgery was close to the predicted value, but postoperative predicted TLC was achieved later than in emphysema patients. A donor-versus-recipient difference in TLC of more than 1L at the time of assessment did not influence the adaptation to the predicted value. FEV1 and vital capacity (VC) rose from means of 70% (SD = 25%) and 63% (SD = 20%) at 1 mo to 96% (SD = 27%) and 91% (SD = 18%), respectively, at 9 mo after HLT. After HLT, TLC returns to the predicted value for the recipient, and not to the preoperative TLC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Use of the Gibbs sampler to estimate transition rates between grades of coronary disease following cardiac transplantation.

Coronary occlusive disease following cardiac transplantation is monitored using serial angiography, and graded on a 3 point scale according to the amount of narrowing observed in major vessels. Disease progression is modelled as a continuous time Markov process. The Gibbs sampler is used to estimate the marginal posterior distributions of the transition rates between grades of disease and from each grade to death.

Adolescent↗
PubMed1992

Error rates with which endomyocardial biopsy specimens are graded for rejection after cardiac transplantation.

Control of the immune response to the transplanted organ is fundamental to the success of transplantation. Endomyocardial biopsy to diagnose and grade rejection is the mainstay in achieving this control. As rejection tends to be a patchy process, accurate diagnosis depends on adequate sampling from the myocardium. This study estimates the error rates with which biopsy specimens are graded. The results of 459 biopsy sets, in which at least 4 fragments were graded, were analyzed. Combinations of grades observed at the same biopsy session were used to estimate error rates. An E-M algorithm was used to estimate error rates. Predictive probabilities of true grades, given a set of 4 graded fragments, were calculated using Bayes theorem. If 4 fragments at a biopsy session were negative there was a 0.02% chance of missing clinically significant rejection (moderate or severe). Similarly, if minimal rejection was the highest grade observed, the probability of missing moderate-severe rejection was negligible, between 0.06 and 0.09%. However, where mild rejection is the highest observed on the 4 fragments, there is between a 2% (1 mild fragment) and 28% (4 mild fragments) chance of moderate-severe rejection being the underlying grade. This study concludes that 4 fragments are adequate as a minimum in most cases. However, if only 4 fragments are available, and greater than or equal to 3 are graded mild, the risk of missing moderate-severe rejection is unacceptably high, and repeat biopsy or treatment may be indicated.

Biopsy↗
PubMed1992

Efficacy of pyrimethamine for the prevention of donor-acquired Toxoplasma gondii infection in heart and heart-lung transplant patients.

Seven (11%) of the first 65 patients who received heart transplants at Papworth Hospital were mismatched for Toxoplasma gondii. Of these, four (57%) experienced T. gondii infection and two died. The remaining two had severe symptoms and received anti-T-gondii chemotherapy for a year after transplantation. In an attempt to reduce the impact of donor-acquired T. gondii in our heart transplant recipients, we decided in April 1984 to give prophylactic pyrimethamine to all T. gondii-mismatched patients. In this study, 7 years later, we review the efficacy of this policy. Five of 37 (14%) patients given prophylactic pyrimethamine acquired T. gondii infection; only one was symptomatic, and none died. This compares with 100% symptomatic infection in the pre-1984 patients, who did not receive prophylactic pyrimethamine. We believe that our experience has shown that pyrimethamine is effective in reducing the incidence and severity of primary donor-acquired T. gondii infection in mismatched heart and heart-lung transplant recipients.

Adolescent↗
PubMed1992

Learning during general anaesthesia: implicit recall after methohexitone or propofol infusion.

Forty-four patients undergoing coronary artery surgery were allocated randomly to receive an infusion of propofol or methohexitone as a hypnotic supplement to a fentanyl-based anaesthetic technique. A taped message was played to the patients, consisting of 10 words associated with prompt sentences and a suggestion for a specific postoperative behavioural response. Twenty patients (10 propofol and 10 methohexitone) (perioperative group) were exposed to the taped message during surgery and in the immediate postoperative period and the other 24 patients (postoperative group) were exposed to the tape only in the postoperative period, after return to the intensive care unit (ICU). No patient had explicit recall of any events during the period when the tape was played. The patients in the propofol group who heard the tape during surgery had significant implicit recall of the word associations compared with the equivalent 10 methohexitone patients (P = 0.004), when tested 48 h after surgery. The patients who were played the tape whilst receiving identical infusion regimens for sedation in the ICU did not demonstrate implicit recall of the word associations in either the propofol or the methohexitone groups. There was no evidence of a response to the specific behavioural suggestion during the postoperative interview. The results confirm that auditory perception can occur during clinically adequate anaesthesia, and that suppression of auditory awareness or learning is a function of both the pharmacological degree of sedation and the degree of surgical stimulation.

Anesthesia, General↗
PubMed1991

Prospective study of quality of life before and after coronary artery bypass grafting.

OBJECTIVES: Measurement of changes in patients' perceptions of how differing states of health affect their lives and determination of the ability of preoperative variables to predict outcome after coronary artery bypass grafting. DESIGN: Prospective study with completion of questionnaires before coronary artery bypass grafting and at three months, one year, and five years afterwards. SETTING: Regional cardiothoracic centre. PATIENTS: 100 Male patients all aged below 60 at the time of operation, who were patients of two cardiothoracic surgeons. MAIN OUTCOME MEASURES: Patients' assessment of their health state in terms of functional capacity and aspects of distress, according to the Nottingham health profile and outcome of operation in terms of changes in symptoms, working life, and daily activities determined by self completed study questionnaires before operation and at three and six months afterwards. RESULTS: Intermediate one year results are reported. The differences between the Nottingham health profile scores before operation and at three months afterwards were significantly different (p less than 0.01), indicating an appreciable improvement in general health state, and at one year compared favourably with those from a normal male population. Analysis of responses to the study questionnaire showed that 65 of 89 patients (73%) were working at one year after operation with a further seven (8%) maintaining that they were fit to work but unable to find employment. The proportion of patients complaining of chest pain fell from 90% (88/98) before grafting to 19% (17/89) at one year after coronary artery bypass grafting, when 91% (81/89) patients maintained that their condition was either completely better or definitely improved. The significant positive factors affecting return to work and home activities were working before operation, short wait for operation, absence of breathlessness, and low physical mobility score in the Nottingham health profile (all p less than 0.001). CONCLUSIONS: Improvements were evident in general health state, symptoms, and activity at three months and one year after coronary artery bypass graft surgery. Interventions likely to influence outcomes included reduction in waiting times for operation; rehabilitation initiatives; and more attention to the quality of information given to patients, their relatives, and the community.

Activities of Daily Living↗
PubMed1991

Cytomegalovirus infection in heart-lung transplant recipients: risk factors, clinical associations, and response to treatment.

The risk factors, clinical associations, and response to treatment of cytomegalovirus (CMV) pneumonia and infection were studied in 65 recipients of heart-lung transplantation. There were 29 episodes of CMV pneumonia in 22 patients. In 80% (20/25) of episodes of CMV pneumonia treated with intravenous ganciclovir, the histologic changes resolved and the patient survived. Among seronegative recipients, a seropositive donor was a significant risk factor for CMV pneumonia and infection in the first 90 days after heart-lung transplantation (P = .004 and .002, respectively). Among seropositive recipients, there was no additional risk associated with a sero-positive donor. Rates of CMV pneumonia and infection were significantly increased when treatment with augmented immunosuppression had been given in the preceding 30 days (P less than .001). A significant association was found between CMV pneumonia or infection and pulmonary bacterial infections occurring 30 days before or after such an episode (P less than .001).

Adolescent↗
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↗
PubMedDate not supplied

Heart transplantation in patients over 54 years of age with triple-drug therapy immunosuppression.

Between April 1, 1986, and December 31, 1989, 206 patients received orthotopic heart transplants with triple-drug therapy immunosuppression (cyclosporine, azathioprine, prednisone). Forty-six patients were aged 55 years or more at the time of transplantation and 160 patients were less than 55 years of age; these two groups were compared. Selection criteria and treatment regimen were the same in both groups. In our experience, although both groups had good postoperative survival, older patients had higher mortality rates early after transplantation, particularly from rejection and infection. Patients over 55 years of age had similar nonfatal rejection rates and were no more likely to have infectious episodes than younger patients. As demand for heart transplantation increases and waiting lists lengthen, the age of potential recipients should be an important factor in deciding how to allocate scarce donated organs, although age should not be exclusive.

Adult↗
PubMedDate not supplied

Influence of recipient and donor gender on outcome after heart transplantation.

To investigate the effect of recipient and donor genders on the outcome after heart transplantation, a retrospective survey was undertaken of 356 patients (366 transplants: 316 males, 40 females) undergoing transplantation between January 1979 and December 31, 1989, at Papworth Hospital. Ninety-three organs came from female donors; 263 organs came from males. Twelve females (30%; 95% confidence interval 16% to 44%) and 51 males (16%; 95% confidence interval 12% to 20%) died in the early postoperative period (within 90 days of operation). To date, two females (5%) and 51 males (16%) have died in the late postoperative period. Comparison between recipient genders showed no statistically significant difference in early mortality rates from any cause or in actuarial survival overall, although fatal acute rejection was significantly more common in female recipients (7 of 40 female recipients versus 19 of 316 male recipients). The higher incidence of fatal rejection among female recipients was related to the higher proportion of female donors in this group, because recipients of female donor grafts had significantly higher mortality rates, particularly in the early postoperative period and as a result of acute rejection, than did recipients of organs from male donors. Death from rejection after the first 3 months and death from infection were not gender-related. Recipients of grafts from female donors did not suffer significantly more early morbidity, such as rejection and infection, or late morbidity in the form of coronary artery disease. Acute rejection episodes were more common in female recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMedDate not supplied

Heart transplantation in the United Kingdom: who waits longest and why.

BACKGROUND: This study aims to identify characteristics that increase the chance of death of potential cardiac transplant recipients before donor organs become available. METHODS: Between June 1, 1988, and May 31, 1993, 332 patients were accepted for heart transplantation; 235 underwent surgery. Ninety-seven patients had not received transplants; of these, 71 died, 13 were transferred to other lists, and 13 were awaiting organs at the close of the study. Median waiting time for those patients who received organs was 109 days, whereas patients who did not receive organs spent a median of 94 days on the list. Recipients are matched to donor organs according to blood group, size (height), and, recently, preoperative transpulmonary pressure gradient. Recently cytomegalovirus antibody mismatches (positive donor to negative recipient) have been avoided where possible. These factors, together with age, gender, underlying diagnosis, previous heart surgery, and Toxoplasma antibody status were studied to assess their influence on waiting time and survival. RESULTS: No characteristics were found significantly to influence survival after acceptance, so that the chance of death while the patient was waiting for heart transplantation is mainly affected by the severity of disease and the length of time a patient waits. In multivariate analyses the following were independently significantly associated with shorter waiting times: small patients (< 1.7 m tall; p = 0.005), patients with blood types B and AB (p = 0.003), and patients with cardiomyopathy (p < 0.001). CONCLUSIONS: These results can be used by cardiologists to help assess the time at which a patient should be referred for transplantation.

Blood Grouping and Crossmatching↗
PubMedDate not supplied

A method of analyzing the onset and progression of coronary occlusive disease after transplantation and its effect on patient survival.

The development of transplant-acquired coronary occlusive disease is monitored with serial angiography and is graded on a three-point scale as normal, mild (< 50% stenosis), or severe (> or = 50% stenosis). Previous studies have provided information about the time to the first sign of disease on angiography or empirical descriptions of progression. The number of observed transitions between grades of disease has been recorded, and a Markov model based on these transitions is used to estimate the rate of progression through angiographically defined disease grades and the mortality rates from each grade. Five hundred thirty-six angiograms from 240 patients were analyzed. Fifty-three graft failures occurred. The annual transition rate per patient year from normal to mild disease was low, 0.120 (95% credible interval, 0.096 to 0.154), although the transition from mild to severe disease was relatively high, 0.482 (95% credible interval, 0.325 to 0.671). Annual death rates from normal, mild, and severe grades were 0.032 (95% credible interval, 0.016 to 0.052), 0.076 (95% credible interval, 0.007 to 0.187) and 0.415 (95% credible interval, 0.244 to 0.640), respectively. Before onset of disease patients have a hazard-free course, and mild disease displayed on angiography is relatively non-life-threatening. However, once mild disease has been detected by angiography, progression to severe disease is rapid, and severe disease carries a very poor prognosis.

Adolescent↗
PubMedDate not supplied

Lack of association between endomyocardial evidence of rejection in the first six months and the later development of transplant-related coronary artery disease.

The development of transplant-related coronary artery disease (TCAD) is the major determinant of long-term heart transplant survival. To test the hypothesis that TCAD might be related to cellular myocardial rejection, the grades of rejection seen at all biopsies performed in the first 6 months after heart transplantation were analyzed in 108 patients who survived more than 6 months. The development of TCAD was assessed at routine follow-up coronary angiography in 101 patients and at necropsy in seven patients. This data was analyzed with Kaplan-Meier survival curves and Cox proportional hazard regression analysis. No significant association was found between either moderate rejection or any level of rejection and the later development of TCAD, nor did the absence of any rejection protect against its development.

Biopsy, Needle↗