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Biomedical subjects

J Wallwork

Publications and source records attributed to J Wallwork.

At least 91 records · Page 5Linked to original sources
PubMed1996

The management of post-cardiac transplantation coronary artery disease.

OBJECTIVE: Allograft coronary artery disease remains the single greatest limitation to long term survival after cardiac transplantation. It is peculiarly aggressive in its behavior and diffuse in its nature. The role of conventional approaches to coronary artery revascularisation were studied in a selected group of cardiac transplant recipients. METHODS: Of the 557 patients undergoing cardiac transplantation at our unit between January 1979 and December 1993, all were screened for the development of allograft coronary artery disease routinely after 2 years and yearly thereafter or after 4 years. Twenty patients with allograft coronary artery disease were considered suitable for treatment by conventional means 17 of whom had undergone transplantation for ischaemic cardiomyopathy and the others for dilating cardiomyopathy. Percutaneous transluminal coronary angioplasty was performed in 18, 25-103 months after transplantation (mean 60 months) all of whom had severe proximal stenoses and reversible defects on perfusion scans. None suffered chest pain. Coronary artery bypass grafting was performed in 5, 95-105 months after transplantation (mean 101 months) 2 of whom had post-infarction unstable angina and 3 had severe triple vessel disease, dyspnoea, and perfusion abnormalities. RESULTS: The primary success rate for PTCA was 84% (16/19). Two lesions restenosed and 3 patients had progressive disease which necessitated coronary revascularisation. No patient died. Of the 5 patients undergoing coronary artery surgery 2 died perioperatively, one from acute left ventricular failure and one from acute rejection. All 18 survivors have improved perfusion scans. Following surgery, all survivors had improvement in dyspnoea and relief of angina. Five late deaths a mean of 89 months after transplantation were from coronary artery disease (4) and lung malignancy (1). CONCLUSIONS: Revascularisation by PTCA and CABG is feasible and successful in selected cardiac transplant recipients. Further study is required to determine the effect of revascularisation on prognosis.

Adult↗
PubMed1996

Permanent pacing in a patient with a left ventricular assist system.

A patient with end stage heart failure underwent permanent implantation of a Novacor left ventricular assist system. Progressive right ventricular dysfunction developed during the first two postoperative weeks. Temporary and subsequently permanent atrioventricular pacing to correct first degree heart block improved the performance of the device, with sustained resolution of his right ventricular failure.

Cardiac Pacing, Artificial↗
PubMed1996

Lung Transplantation in patients with systemic diseases: an eleven-year experience at Papworth Hospital.

BACKGROUND: The presence of a systemic disease has traditionally been considered a contraindication to lung transplantation. METHODS: We present a retrospective review of 19 patients undergoing lung transplantation for end-stage pulmonary disease associated with a systemic illness since 1984. There were 11 male and 8 female patients, aged from 23 to 59 years (median 43 years) with end-stage pulmonary involvement by sarcoidosis (11 patients), Langerhan's cell histiocytosis (three patients), systemic vasculitis (four patients: three with systemic lupus erythrematosis, one with Churg-Strauss), and common variable immunodeficiency (one patient). Ten patients received a heart-lung transplant, and eight patients received a single lung transplant. One patient underwent single lung transplantation after an earlier heart-lung transplant. RESULTS: The 30-day mortality was 5.3%. Nine patients died overall. Two of these had systemic lupus erythrematosis with anticardiolipin antibodies and died from complications of their underlying vasculitis. The mean 1- and 2-year actuarial survivals for all patients were 71% (standard error +/- 10.8%) and 64% (standard error +/- 11.9%), respectively. All patients surviving longer than 3 months achieved an improvement in functional status to New York Heart Association class I or II, and a significant increase occurred in mean forced expiratory volume in 1 second and forced vital capacity. Disease recurrence without clinical significance occurred in two patients with sarcoidosis. Of the nine patients who died, seven had autopsies and none showed evidence of disease recurrence in the lungs. CONCLUSIONS: Patients with systemic diseases can be considered for lung transplantation and each case should be judged on its individual merits. However, patients with systemic lupus erythrematosis (particularly when associated with anticardiolipin antibodies) should probably not be offered lung transplantation because they are likely to develop further complications of their underlying vasculitis.

Actuarial Analysis↗
PubMed1996

Surgical angioplasty of the left main coronary artery: follow-up with magnetic resonance imaging.

BACKGROUND: Ostial stenosis of the left main coronary artery is a serious condition with a dismal prognosis. The treatment is surgical, with the two viable options being coronary artery bypass grafting and surgical angioplasty of the left main coronary artery. METHODS: We describe the use of surgical angioplasty to treat 3 patients (2 women and 1 man) with left main ostial stenosis using the posterior approach. Patency of the angioplasty was demonstrated subsequently with magnetic resonance imaging. RESULTS: All 3 patients were free of angina 12, 18, and 24 months after operation. Magnetic resonance imaging scans in all 3 patients demonstrated the widely patent left main coronary artery. CONCLUSIONS: Surgical angioplasty is an effective alternative to coronary artery bypass grafting in patients with left main ostial stenosis. Magnetic resonance imaging is an excellent noninvasive method for monitoring the patency of the left main coronary artery.

Adult↗
PubMed1996

Heart-lung-liver transplantation.

We report three patients with cystic fibrosis and one patient with primary biliary cirrhosis and plexogenic pulmonary hypertension who have undergone heart-lung-liver transplantation as a combined procedure. Liver transplantation was necessary in the three patients with cystic fibrosis because of portal hypertension secondary to either hepatic fibrosis or established cirrhosis in addition to their advanced lung disease. Three of the four patients were alive at 20, 50, and 100 months after transplantation (one patient with cystic fibrosis died on day 16 of pneumonia) with well-preserved pulmonary function (forced expiratory volume in 1 second 110%, 49%, and 100% predicted, respectively), normal hepatic function and New York Heart Association class 1 performance status. Heart-lung and concurrent liver transplantation is a feasible and successful procedure with a satisfactory long-term outcome in selected patients with advanced pulmonary and hepatic disease.

Adult↗
PubMed1996

Measurement of health-related quality of life before and after heart-lung transplantation.

BACKGROUND: The measurement of the quality of the outcome of treatment as viewed by patients is becoming increasingly recognized as an important aspect of decision making in all health services. This major study, which set out to measure the health-related quality of life outcomes of heart and lung transplantation, developed from the experience gained in the United Kingdom and United States studies of the cost and benefits of heart transplantation in the 1980s. METHODS: The design was prospective with a cohort of patients completing a variety of generic and specific health-related quality of life questionnaires at intervals before and after heart and lung transplantation. The sample size was not prescribed; one of the aims of the project was to test the feasibility of introducing routine monitoring of health-related quality of life outcomes as an integral part of a developing transplant service. RESULTS: Before the operation, there was evidence of deterioration over time in all dimensions of the Nottingham Health Profile. In comparing Profile scores at less than 3 months before with those at 3 to 6 months after transplantation, statistically significant improvements were evident (p < 0.001). Mean scores at intervals up to 2 years after transplantation showed little change over time and compared well with those from a general population sample. Hospital Anxiety and Depression Scale scores were reduced significantly (p < 0.01) by 1 year after heart and lung transplantation. In the pretransplantation period, at least 90% of 101 patients had some level of restriction in home and leisure activities, reducing to between 2% and 24% at 1 year after transplantation. Similarly, 79 patients (78%) had chest pain, and 101 (100%) were breathless before transplantation, reducing to 54% and 39%, respectively, at 1 year after surgery; by which time, for 8 of 10 patients, the problem was occasional. CONCLUSIONS: Highly significant improvements were observed in the physical, social, and emotional dimensions of health-related quality of life of patients after heart-lung transplantation. The advantages and feasibility of combining generic and condition-specific questionnaires are shown together with the need to develop new measures with greater sensitivity to the smaller peaks and troughs of recovery.

Activities of Daily Living↗
PubMed1995

Blood cyclosporine concentrations and cytomegalovirus infection following heart transplantation.

We have attempted to identify major risk factors for cytomegalovirus (CMV) infection and disease following heart transplantation, with emphasis on the degree and type of immunosuppression used. One hundred and eleven consecutive heart transplant recipients were studied for the first 4 months. Data from the 95 who survived at least 1 month were analyzed using multiple Cox regression. Blood cyclosporine concentrations (CsAbc) > 550 micrograms L-1 were associated with a 4.4-fold increase in risk of CMV infection during the next week (95% confidence interval = 1.2-16.2). Other significant risk factors for CMV infection included antirejection treatment in the past 14 days, a drop in white blood cell count, receiving a CMV antibody-positive donor organ, and primary diagnosis other than cardiomyopathy. We found that patients experiencing a CMV infection were at 3 times the risk of subsequently developing symptomatic CMV disease (95% confidence interval = 1.1-9.7). In addition, the proportion of patients developing symptomatic CMV disease was significantly higher amongst those with a median CsAbc > 550 micrograms L-1 for at least 1 week (29% vs. 10%; P = 0.02) or who had been treated for rejection more frequently than once every 6 weeks (31% vs. 12%; P = 0.04) during the first 4 months. CMV antibody-negative recipients of antibody-positive donor organs had a higher rate of symptomatic CMV disease than did other serological combinations (67% vs. 10%; P = 0.0001). We conclude that the risk of CMV infection and symptomatic disease following heart transplantation may be critically influenced by early management of immunosuppression as well as by donor serology.

Cyclosporine↗
PubMed1995

Tissue expression of human complement inhibitor, decay-accelerating factor, in transgenic pigs. A potential approach for preventing xenograft rejection.

Since complement-mediated hyperacute rejection of xenografts prevents the use of pigs as organ donors to man, the development of transgenic animals expressing species-specific complement inhibitors could provide a strategy for overcoming hyperacute rejection. The complement inhibitor, human decay-accelerating factor (hDAF), prevents the assembly of C3 and C5 convertases. In this article, the first histologic analysis of hDAF expression in pig tissues, specifically expression in endothelial cells of pigs transgenic for hDAF, is described. Twenty-seven transgenic pigs were categorized into 4 groups based on the expression patterns in endothelial, vascular smooth muscle, and squamous epithelial cells of skin biopsy specimens. Skin biopsy specimens permitted evaluation of the pigs without the need to kill them or to perform invasive procedures. Sixteen cases demonstrated endothelial cell staining. Complete necropsy evaluation, available in 14 of the 27 pigs, correlated with the skin biopsy specimen expression of hDAF. The immunoperoxidase data matched identically with the presence of the mRNA transcript in 25 of the 26 cases where RNA data were available. Also, the staining patterns of 6 transgenic pig founders and their 9 offspring (total of 9 founder-offspring pairs) correlated. Since transgenes are variably expressed in different cell types and since tissue lysates represent a melange of cell types, histologic evaluation for protein expression in tissues from transgenic animals will be critical if they are to be bred to become clinical organ donors. In addition to endothelial expression of hDAF, its expression on vascular smooth muscle cells may be important in preventing tissue damage when breaks in the endothelium occur.

Animals↗
PubMed1995

Relative bioavailability of cyclosporin from conventional and microemulsion formulations in heart-lung transplant candidates with cystic fibrosis.

Patients with cystic fibrosis absorb cyclosporin poorly and erratically. We have compared the relative bioavailability of cyclosporin from conventional and microemulsion formulations in 5 adult heart-lung transplant candidates with cystic fibrosis. Relative bioavailability was compared at two dose levels (200 mg and 800 mg). A randomized 4-period cross-over study was performed with at least a 7 day washout period between each single dose pharmacokinetic study. Blood cyclosporin concentrations were measured by a selective monoclonal antibody-based radioimmunoassay. The bioavailability of cyclosporin from the microemulsion formulation was 1.84 (95% C.I. 1.05 to 3.22; P = 0.04) and 2.09 (95% C.I. 0.95 to 4.61; P = 0.06) times higher compared with the conventional formulation at 200 mg and 800 mg respectively. Cmax following the microemulsion formulation was 3.38 (C.I. 1.14 to 10.59; P = 0.04) and 2.77 (C.I. 1.48 to 5.19; P = 0.01) times higher compared with the conventional formulation at 200 mg and 800 mg respectively. The higher Cmax following the microemulsion formulation was accompanied by shorter tmax. An enhancement of cyclosporin absorption with the microemulsion formulation was demonstrated in each patient for at least one dose level. We conclude that rate and extent of cyclosporin absorption from the microemulsion formulation is greater compared with the conventional formulation in patients with cystic fibrosis. The potential therapeutic and economic benefits of the microemulsion formulation should be evaluated in cystic fibrosis patients following heart-lung transplantation.

Adult↗
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

The control of hyperacute rejection by genetic engineering of the donor species.

Activation of endogenous complement is inhibited both in the soluble phase and at the membrane surface by a group of structurally similar proteins. A possible solution to hyperacute rejection is to produce donor animals transgenic for human complement regulators. Mouse cells expressing the human complement regulatory proteins decay accelerating factor (DAF) or membrane cofactor protein (MCP) were produced both by hybridoma technology and by transfection with the appropriate cDNAs. The expression of either or both of these products protected the mouse cell from lysis by human (though not rabbit) complement in the presence of naturally occurring human anti-mouse antibody. This effect could be abrogated by the addition of monoclonal antibody against DAF or MCP. Hyperacute rejection of discordant organ xenografts is mediated by human complement. A 6.5 kilobase minigene for DAF has been microinjected into porcine fertilised ova. Forty-five pigs transgenic for human DAF have been produced. Of these, 65% transcribe message. The amount of message produced varied substantially from animal to animal and was independent of copy number integrated. Expression of human DAF on the porcine lymphocyte surface could be detected and this was able to downregulate human complement activation. Amounts of protein expressed on different tissues varied both from pig to pig and within animals from tissue to tissue. The pigs grow and develop normally with no evidence of ill effects due to possession of the transgene.

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↗
PubMed1995

Single lung transplantation for end stage emphysema.

BACKGROUND: The first successful single lung transplantation was carried out in 1983 for pulmonary fibrosis. Because of the inherent advantages of single lung transplantation, a transplantation programme has been started for patients with end stage lung disease due to emphysema. METHODS: Between October 1990 and August 1993 25 patients with severe emphysema (15 men, mean age 51 years) received a single lung transplant at our institution. All patients were severely disabled with a mean (SD) 12 minute walking distance of 281 (165) metres. There were five deaths in the series, four in the first 20 days and one on day 503. Two patients suffered graft compression by air trapping in the native lung. Bronchial narrowing requiring insertion of endobronchial stenting occurred in four patients. RESULTS: Mean (SD) FEV1 improved from a preoperative value of 17.8(13%) predicted to a six month value of 53.6(13)%, and FEV1/FVC from 23.8(12)% to 68.6(15)%. After the transplant 12 patients are in New York Heart Association (NYHA) class I and the rest of the survivors are in NYHA II. Actuarial survival was 82% at one year and 74% at three years. CONCLUSIONS: Single lung transplantation is an effective treatment for end stage lung disease due to emphysema and carries an acceptable mortality and morbidity.

Adult↗