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Biomedical subjects

J Wallwork

Publications and source records attributed to J Wallwork.

At least 235 records · Page 13Linked to original sources
PubMed1990

Lung function associated with histologically diagnosed acute lung rejection and pulmonary infection in heart-lung transplant patients.

A group of 34 heart-lung transplant patients were studied with serial pulmonary function measurements, chest radiographs, and transbronchial biopsies from the time of surgery. These investigations were carried out routinely at 3 and 6 months and then annually after transplantation as well as on clinical suspicion of acute lung rejection or infection. A total of 61 transbronchial biopsies and concurrent lung function and chest radiographs were obtained. Of the biopsies, 30 (49.2%) showed histologic evidence of lung rejection, 12 (19.7%) demonstrated various opportunistic infections, and 19 (31.1%) were normal. Compared to during episodes of normal biopsies, FEV1 decreased significantly with lung rejection (p less than 0.001) and with infection (p less than 0.01). Vital capacity (VC) and DLCO also fell with these acute lung complications. Using histologic diagnosis as a standard, lung function testing had a sensitivity of 86% in detecting lung rejection in the first 3 months postoperation and 75% in the subsequent period. Its sensitivity for detecting lung infection was 75%. Although not distinguishing between these two complications, lung function had a specificity of 84% for detecting occurrence of an acute lung complication. Chest radiographs, although of similar sensitivity in the first 3 months postsurgery, had a sensitivity of only 19% for rejection in subsequent months and 58% for infection. Its specificity was 100%. Lung function testing changes in a predictable fashion with lung rejection and infection, offers an improvement over chest radiographs, and provides a quantitative measurement to aid the decision of when to undertake transbronchial lung biopsy.

Biopsy↗
PubMed1990

Myocardial localization and isoforms of neural cell adhesion molecule (N-CAM) in the developing and transplanted human heart.

Neural cell adhesion molecule (N-CAM) has been implicated in cellular interactions involved in cardiac morphogenesis and innervation. Immunohistochemical techniques and Western blot analysis were used to determine the localization and isoforms of N-CAM in the developing and extrinsically denervated human heart. Myocardial and conducting cells in the fetal heart (7-24 wk gestation) exhibited sarcolemmal immunoreactivity, the major desialo N-CAM isoforms being 150, 145, 120, 115, and 110 kD. N-CAM expression appeared to be downregulated in the myocardium during adult life, with relatively little sarcolemmal immunoreactivity being detected in normal donor tissues. In contrast to the temporal changes observed in the myocardium, both the developing and mature cardiac innervation displayed N-CAM immunofluorescence staining, localized to neuronal cell bodies, nerve fascicles and fibres. Extrinsically denervated cardiac allografts, obtained 2 d to 91 mo after transplantation, showed extensive sarcolemmal and intercalated disc immunostaining and expression of 125-, 120-, and 115-kD isoforms. Tissues from explanted recipient hearts and atrial appendage samples obtained during coronary bypass graft operations were also examined and displayed varying amounts of N-CAM immunoreactivity. We conclude that the expression of N-CAM immunoreactivity and isoforms in the human heart is developmentally regulated and may be modulated by factors such as cardiac innervation and myocardial hypertrophy.

Adult↗
PubMed1990

The use of home spirometry in detecting acute lung rejection and infection following heart-lung transplantation.

The value of home spirometry in detecting acute lung rejection and opportunistic infections was studied in 15 heart-lung transplant recipients over a six-month period. The patients measured their FEV1 and FVC twice daily at home using a portable turbine spirometer. The records were then reviewed in relation to the results of transbronchial lung biopsy carried out during occurrences of respiratory symptoms and during routine posttransplant assessment. FEV1 and FVC fell by a mean (+/- SD) of 10.4 +/- 6.9 percent and 9.3 +/- 7.9 percent, respectively, during 20 episodes of lung rejection. The corresponding figures during opportunistic infections were 12.8 +/- 10.1 percent and 12.5 +/- 14.3 percent. No such change was observed during routine normal biopsies. Regular home spirometry offered early detection of these complications allowing early transbronchial lung biopsy as well as assessing efficacy of their therapy. Above all, measurements can be made daily, which is unique in the assessment of solid organ transplants.

Acute Disease↗
PubMed1990

The acute effect of the synthetic prostacyclin analogue iloprost in primary pulmonary hypertension.

Twelve patients with severe primary pulmonary hypertension and pronounced disability unresponsive to oral vasolidators were assessed as to their suitability for heart-lung transplantation. During routine right heart catheterisation, intravenous infusions of both prostacyclin (PG1(2] and its synthetic analogue, iloprost (IL), were given in random order. The dose of each drug was increased whilst the improvements in cardiac output (Q) and pulmonary vascular resistance (PVR) were recorded. The maximum rate of each infusion was determined by the onset of side effects or a fall in mean systemic blood pressure of more than 20 per cent. The mean maximum dose of PG1(2) was 6 +/- 2 ng/kg/min and that of IL 3.4 +/- 1.8 ng/kg/min, and both infusions achieved similar haemodynamic effects. In this open, randomised study, intravenous IL was as effective as prostacyclin in lowering PVR, but with a lower infused dose. Iloprost may have an important role in the acute assessment of patients with primary pulmonary hypertension, and when available for prescription should be assessed as an alterative long-term intravenous vasodilator to prostacyclin.

Adult↗
PubMed1990

Transplantation of the lung.

The introduction of cyclosporine as a highly effective immunosuppressive agent and the development of new techniques for heart-lung and lung transplantation have led to a new treatment for a wide range of fatal cardiopulmonary diseases. Indications for surgery are now becoming clear, together with major contra-indications. Suppurative lung disease, such as cystic fibrosis, can be effectively treated by heart-lung transplant (HLT). A whole new field of pulmonary medicine is emerging to provide the physiological monitoring and diagnostic techniques for major complications such as opportunistic lung infection and pulmonary rejection. Obliterative bronchiolitis, a consequence of frequent and severe rejection, still provides a major challenge to the immunological scientist and respiratory physician. Lung transplantation, by disrupting the vascular supply and innervation of the lung, is raising major questions about the generally accepted beliefs of regulation of breathing and pulmonary mechanics. Finally, as the survival rate improves beyond the current 50% at 3 yrs, lung transplantation will perhaps present further challenges to our understanding of the pathogenesis of various diseases such as asthma and cystic fibrosis.

Graft Rejection↗
PubMed1990

Transbronchial biopsies in children after heart-lung transplantation.

Sixty transbronchial biopsies have been performed in eight children after heart-lung transplantation. The selection of fiber-optic bronchoscope or a small (4 mm; 30 cm) rigid bronchoscope was made according to the size of endotracheal tube required at surgery. If the endotracheal tube was size 7.5 or greater, a fiber-optic bronchoscope was used, whereas if the endotracheal tube size was below 7, a rigid bronchoscope was used. For the diagnosis of lung rejection, the histology of biopsies revealed a sensitivity of 91% and specificity of 69% (similar to the result in adults). The histology also distinguished lung infection from rejection. Complications included three pneumothoraces and two clinically significant episodes of hemorrhage, one of which led to a cardiorespiratory arrest, which may have been caused by hypoxia. As a result, arterial oxygen saturation is now monitored during the procedure using a pulse oximeter.

Adolescent↗
PubMed1990

Acetylcholine and adenosine diphosphate cause endothelium-dependent relaxation of isolated human pulmonary arteries.

Endothelium-dependent vasorelaxation mediated by endothelium-derived relaxing factors (EDRF) has been extensively studied in animals but only limited studies in man are available. Demonstration of EDRF-mediated dilatation of human vessels is fundamental for understanding the mechanisms of vascular diseases in man. We have investigated endothelium-dependent relaxation of isolated human pulmonary arteries. Vascular segments, taken from uninvolved regions of resected lung from eight patients undergoing lobectomy for lung carcinoma, were cut into rings. In rings precontracted with phenylephrine, both acetylcholine (ACh) and adenosine diphosphate (ADP) induced dose-dependent relaxation in the presence of endothelium but not when the endothelium had been carefully removed. The rings without endothelium relaxed completely with sodium nitroprusside, a vasodilator agent acting directly on vascular smooth muscle. Pre-incubation with indomethacin, a cyclo-oxygenase inhibitor which blocks production of prostacyclin, did not alter the vasorelaxant responses to ACh and ADP, suggesting that one (or several) non-prostanoid EDRF(s) are responsible for the endothelium-dependent relaxation of isolated human pulmonary arteries.

Acetylcholine↗
PubMed1990

Cross-correlation of cyclosporine concentrations and biochemical measures of kidney and liver function in heart and heart-lung transplant recipients.

Cross-correlation of cyclosporine concentrations with results of biochemical tests of renal and liver function, measured during the first three months post-operatively, was carried out retrospectively in 24 heart and eight heart-lung transplant recipients to assess the temporal relationship between cyclosporine treatment and the development of possible toxic side-effects. We found a statistically significant negative correlation (95% confidence interval of the mean correlation coefficient did not overlap zero) between the five-day mean concentration of cyclosporine in whole blood (but not plasma) as measured with nonselective (NSRIA) and selective radioimmunoassays (SRIA) and the mean reciprocal creatinine concentration measured in the subsequent five days. In 15 of 32 (47%) patients the negative correlation coefficient exceeded 0.7 (high susceptibility), whereas in 11 of 32 (34%) it was between 0.5 and 0.7 (medium susceptibility), and in only six of 32 (19%) was it less than 0.3 (low susceptibility). We found no consistent correlations between cyclosporine measurements and results of other renal-function tests or liver-function tests. This suggests that therapeutic doses of the drug are not hepatotoxic in most patients. There was, however, a significantly correlated decrease in the NSRIA/SRIA ratio and in serum bilirubin concentration with time post-operatively, reflecting improvement in hepatic function and clearance of the cyclosporine metabolites that are detected by NSRIA. Assays of cyclosporine in whole blood, but not in plasma, are of value in anticipating changes in renal function after heart and heart-lung transplantation.

Biomarkers↗