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Biomedical subjects

J Wallwork

Publications and source records attributed to J Wallwork.

At least 271 records · Page 15Linked to original sources
PubMed1989

Airway mucosal bioelectric potential difference in cystic fibrosis after lung transplantation.

Bioelectrical potential difference (PD) across the respiratory mucosa is raised in cystic fibrosis (CF). We have recorded airway potentials from seven patients with CF who had undergone heart-lung transplantation and from eight patients without CF who had had transplants for cardiovascular disease; comparison of these populations controls for the effects of denervation and immunosuppressive treatment. Six patients without CF who had not had transplants formed an additional control. PD was recorded during routine fiberoptic bronchoscopy, using a Ringer's-perfused exploring bridge connected across a high impedance amplifier to an intravenous reference bridge. Bronchial lavage and sputum culture revealed no evidence of infection. Bronchial PD was similar in all three groups of patients at equivalent sites. However, nasal PD was raised in the CF group (mean value, 44 mV +/- 3.9 SE) compared with the patients who had transplants for cardiovascular disease (mean, 18 mV +/- 1.1 SE), and the control patients (mean, 15 mV +/- 1.2 SE). We conclude that the epithelial defects that result in raised airway potentials in CF do not recur in the transplanted lung.

Adolescent↗
PubMed1989

The importance of cytomegalovirus in heart-lung transplant recipients.

The first 33 heart-lung transplant recipients in our series were studied for evidence of CMV infection. CMV infection was diagnosed by a change in the serologic status, viral culture, or histology of lung tissue. Of 18 patients who were preoperatively negative for CMV antibody, eight received organs from CMV antibody-positive donors. Five developed pneumonitis (fatal in three)l; one survived primary CMV of the GI tract. Those who recovered from CMV pneumonitis received IV ganciclovir with CMV hyperimmune globulin given prophylactically from the time of transplantation. Only three of ten antibody-negative patients receiving organs from antibody-negative donors developed primary CMV, characterized by only fever in two but associated with rejection, and repeated infection was fatal in a third. CMV reactivation/reinfection occurred in seven of 15 (47 percent) without clinical disease in all but one case. Following heart-lung transplantation, CMV is the cause of considerable mortality and morbidity. We recommend that CMV antibody-negative recipients should receive organs only from antibody-negative donors. If a donor/recipient mismatch occurs, hyperimmune globulin and ganciclovir may improve survival.

Adult↗
PubMed1989

Pulmonary vasodilation with prostacyclin in primary and secondary pulmonary hypertension.

Twenty-three patients with pulmonary hypertension underwent right cardiac catheterization and measurement of their response to a short-term infusion of prostacyclin. Pulmonary vasodilation with a greater than 20 percent fall in PVR occurred in all five patients with primary pulmonary hypertension where the predominant lesions were plexogenic; in three out of five patients where the predominant lesions were thrombotic; in three out of five patients with pulmonary hypertension and obstruction of proximal vessels; in three out of five patients with COPD; in both patients with pulmonary fibrosis due to sarcoidosis; and in the one patient with pulmonary veno-occlusive disease, where the pulmonary vasodilation was offset by a fall in arterial oxygen content. Prostacyclin is a safe and effective drug to use for testing the response of the pulmonary circulation to a vasodilator in pulmonary hypertension due to different causes. Short-term testing for a vasodilator response, with a view to instituting long-term therapy, should not be restricted to those patients with primary pulmonary hypertension due to plexogenic pulmonary arteriopathy.

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↗
PubMed1989

[Clinical applications of the heart-lung transplant. Clinical results 5 years after the start of the program at Papworth].

In this study is reviewed the experience at Papworth Hospital, Cambridgeshire, and Great Ormond Street Hospital, London, with combined heart-lung transplantation. Between April 1984 and June 1989, 73 patients have undergone heart-lung transplantation. Donors and recipients were carefully matched with regards to serology, morphology and cytomegalovirus compatibility. Heart preservation was based on use of cold St. Thomas' cardioplegic solution; a pulmonary preservation fluid has been developed that allows distant organ procurement with a single pulmonary artery flush technique (Papworth solution). The recipients were: 21 pts with Eisenmenger's syndrome, 15 pts with pulmonary hypertension, 37 pts with pulmonary disease (including 22 cystic fibrosis). The results are: no surgical mortality; no acute cardiac rejection episodes. Twenty-three patients died (16 with infections, 3 with obliterative bronchiolitis, 2 with cerebral embolism and 2 others). The actuarial survival rate at one year is 73.2%; 63% at two years and 47.4% at four years. The use of transbronchial biopsy of the lung has provided accurate early and safe diagnosis of pulmonary rejection. Development in organ preservation and patient management, as well as careful selection of recipients and donors, have led to the effective use of resources and thereby to these good results.

Adolescent↗
PubMed1989

The effect of recipient lung size on lung physiology after heart-lung transplantation.

We studied the postoperative course of lung volumes in 32 heart-lung transplant recipients relative to the predicted total lung capacity of the individual donors, to assess the degree of inaccuracy likely to result from the radiological method of matching of donor and recipient lung sizes. There was a tendency for recipients with large preoperative lung volumes--from, for example, emphysema--to receive smaller lungs, while those with smaller volumes from pulmonary vascular disease received bigger donor lungs, but no immediate problems were incurred. After an initial fall in total lung capacity, the postoperative value of the total lung capacity approached the recipients' pretransplant value about one year after the operation irrespective of the size of the donor lungs. This suggests that chest wall compliance is the major determinant of postoperative lung volume and not the donor lung size or compliance. Exact matching of donors' and recipients' lung sizes may not be necessary, and if required can be simply achieved by comparing the measured total lung capacity in the recipient with the predicted value of the donor based on sex, age, and height.

Anthropometry↗
PubMed1988

Changes in factor VIII proteins after cardiopulmonary bypass in man suggest endothelial damage.

16 patients undergoing coronary artery bypass grafting using cardiopulmonary bypass (CPB) had blood samples taken at various times before, during and up to 1 week after surgery for estimation of beta-thromboglobulin (BTG), alpha-1-antichymotrypsin (ACT), factor VIII procoagulant protein (VIII:C), von Willebrand factor antigen (vWF:Ag) and ristocetin co-factor (vWF:RiCoF). vWF:Ag and vWF:RiCoF rose during and following surgery in a different manner to ACT. At 1 week there was a significantly disproportionate rise in vWF:Ag compared to vWF:RiCoF which suggested a degree of pulmonary endothelial damage. Prostacyclin, which was administered to 8 of the patients during CPB, reduced platelet activation as measured by a reduction in the release of BTG and also attenuated the consumption of VIII:C. It had no effect on pulmonary endothelial damage as measured by the ratio of vWF:Ag to vWF:RiCoF.

Adult↗
PubMed1988

Heart-lung transplantation for cystic fibrosis.

13 patients with severe lung disease and cor pulmonale from cystic fibrosis were accepted for heart-lung transplantation (HLT). 6 have had the operation, of whom 5 are well, with normal lung function, 3-29 months after operation. 1 patient died from adult respiratory distress syndrome after reoperation to control persistent chest-wall bleeding: at necropsy, this patient proved to have cirrhosis. Respiratory tract infections and acute lung rejection after HLT for cystic fibrosis were no more common than in other HLT patients. Of the 7 patients for whom suitable donor organs were not found, 3 died within 3 months of assessment. Initial severity of disease had been similar to that in the transplant group. The cost of assessment, operation, and 1 year's treatment after HLT is similar to that of medical treatment for such patients.

Adult↗
PubMed1988

Heart-lung transplantation: better use of resources.

PURPOSE: Our goal was to review the experience at Papworth Hospital, Cambridgeshire, England, with combined heart-lung transplantation. PATIENTS AND METHODS: Since April 1984, 31 patients have undergone heart-lung transplantation. Donors and recipients are carefully matched with regards to serology, morphology, and cytomegalovirus compatibility. A pulmonary preservation fluid has been developed that allows distant organ procurement with a single pulmonary artery flush technique. RESULTS: Acute cardiac rejection has not occurred in these patients. Twenty-three patients are alive between two months and over three years following transplantation. The actuarial survival rate at one year is 78 percent, and 70 percent at two years. Three patients died as a result of cytomegalovirus pneumonitis; in two patients, obliterative bronchiolitis developed, and both died, one after an opportunistic infection developed. Three patients died from other causes. The use of transbronchial biopsy of the lung has provided accurate, early, and safe diagnosis of pulmonary rejection. CONCLUSION: Developments in organ preservation and patient management, as well as careful selection of recipients and donors, have led to the effective use of resources and thereby to these good results. In particular, the incidence of obliterative bronchiolitis has been low, which is attributed to the early treatment of pulmonary rejection following diagnosis by transbronchial biopsy.

Adolescent↗
PubMed1988

Cyclosporin A in cardiac transplantation: medium-term results in 62 patients.

Between March, 1982, and October, 1984, 62 patients underwent orthotopic cardiac transplantation in our institution. Immunosuppression was based on cyclosporin A (Cy A) and low-dose steroids with an initial 10-day course of antithymocyte globulin. Follow-up ranged between 39 and 71 months (mean, 51.7 months). Actuarial survival at 1 year through 5 years was 80.6%, 77.4%, 74.2%, 71.4%, and 63.5%, respectively. Graft atheroma led to graft failure in 6 patients, 4 of whom died between 23 and 55 months after transplantation and 2 of whom had a repeat transplantation at 32 and 53 months. Diastolic hypertension (90 mm Hg or higher) developed in 88% of patients at 1 year. Chronic renal impairment was evident in all patients who survived for 2 years. Mean serum creatinine preoperatively and at 1 year through 4 years was 1.49 +/- 0.08 mg/100 ml (+/- the standard error), 2.01 +/- 0.09 mg/100 2.07 +/- 0.09 mg/100 ml, 2.26 +/- 0.19 mg/100 ml, and 2.32 +/- 0.33 mg/100 ml, respectively. End-stage renal failure requiring regular hemodialysis developed in 3 patients, 2 of whom died. We conclude that in addition to graft atheroma, Cy A-related nephrotoxicity is emerging as a major cause of medium-term and long-term morbidity and mortality. The use of lower doses of Cy A in a triple-therapy protocol, that is, Cy A, azathioprine, and low-dose steroids, could help reduce the extent of renal impairment.

Adolescent↗
PubMed1988

Transbronchial lung biopsy for the diagnosis of rejection in heart-lung transplant patients.

Long-term success of human lung transplantation has been hindered by the lack of an effective and repeatable method of obtained tissue from the transplanted lung for histology. Management of patients is complicated by the difficulty in distinguishing clinically between opportunistic infection of the lung and rejection. As a result, a large number of patients in recent reports develop chronic disabling obliterative bronchiolitis, believed to be the consequence of "chronic" rejection. Twenty-one patients have undergone heart-lung transplantation in our institute since 1984. During fiberoptic bronchoscopy, 43 transbronchial lung biopsies were performed in 15 patients. Twenty episodes of rejection occurred in 11 patients, from whom 16 sets of biopsies showed the typical changes of perivascular infiltrate and mucosal inflammation. Three biopsies were falsely negative; six routine biopsies performed when patients were well were all normal. Overall sensitivity was 84% and specificity 100%. By contrast, the sensitivity of the chest radiograph was only 40%. Opportunistic lung infection in 8 patients was diagnosed by transbronchial biopsy with a sensitivity of 38% and specificity of 100%. In no patient with opportunistic infection were the histologic features of rejection seen. Transbronchial lung biopsy offers a safe and repeatable method to obtain tissue from heart-lung transplants for histology. It has enabled the management of the lung transplant patient to be equivalent to that of the kidney, liver, and heart transplant patient.

Biopsy↗
PubMed1988

Localisation of atrial natriuretic peptide immunoreactivity in the ventricular myocardium and conduction system of the human fetal and adult heart.

Atrial natriuretic peptide immunoreactivity was found in ventricular and atrial tissues with specific antisera raised to the amino and carboxy terminal regions of the precursor molecule. In 13 developing human hearts (7-24 weeks' gestation) the immunoreactivity was concentrated in the atrial myocardium and ventricular conduction system but it was also detected in the early fetal ventricular myocardium. Immunoreactivity in five normal adults was largely confined to the atrial myocardium although it was also found in the ventricular conduction tissues of hearts removed from 10 patients who were undergoing cardiac transplantation. The ventricular conduction system is an extra-atrial site for the synthesis of atrial natriuretic peptide. In the failing heart this synthesis may be further supplemented by expression of the gene in the ventricular myocardium. It is possible that ventricular production of the peptide contributes to the raised circulating concentrations of atrial natriuretic peptide immunoreactivity found in severe congestive heart disease, particularly in patients with dilated cardiomyopathy.

Adolescent↗
PubMed1988

Cardiac surgery for patients aged 65 years and older: a long term survival analysis.

Between January 1973 and December 1984, 562 patients aged greater than or equal to 65 had cardiac surgery at Papworth Hospital. Most had mitral or aortic valve replacements (coronary artery bypass grafting was not introduced for this age group at Papworth until 1977). The overall operative mortality, defined as death within thirty days or death before leaving hospital, was 7.3%. There were no early deaths in patients undergoing coronary artery bypass grafting surgery. Questionnaires sent to general practitioners in East Anglia traced 86.0% of the patients who survived to leave hospital. The longer term survival rates for all patients were 88.0%. (95% confidence interval (CI) 85 to 91) at one year and 74.4% (95% CI 69 to 79) at five years. The rates for those patients who survived the initial few months were 96.3% (95% CI 94 to 98) at one year and 81.5% (95% CI 77 to 86) at five years and these rates were no different from those in the general population aged greater than or equal to 65.

Aged↗
PubMed1988

Cytomegalovirus infections in heart and heart and lung transplant recipients.

Of the first 166 heart and 15 heart and lung transplant recipients at Papworth Hospital, Cambridge, who survived for more than one month after transplantation, 162 were investigated for cytomegalovirus (CMV) infection by serological methods. Altogether, 73 (45%) developed CMV infection after transplantation: 30 (18.5%) had acquired primary infection and 43 (26.5%) reactivation or reinfection. Six patients died of primary infection, probably acquired from the donor organ. Recipients negative for CMV antibody who received an organ from an antibody positive donor had the most severe disease. Heart and lung transplant recipients experienced more severe primary CMV infection than those in whom the heart alone was transplanted. The most sensitive and rapid serological method was a mu-capture enzyme linked immunosorbent assay (ELISA) for detecting CMV specific IgM, the amount of which was often of prognostic value and influenced the management of patients.

Adolescent↗