Biomedical subjects
Publications and source records attributed to J R Pepper.
The histological, immunocytochemical, and electron microscopic findings in a case of malignant primary pulmonary paraganglioma are reported. The existence of this rare tumour is evidence for the presence of pulmonary chemoreceptors.
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We describe the management of bronchopleurobiliary fistula in a 56-year-old woman who underwent a (L) mastectomy with postoperative radio- and chemotherapy for advanced breast carcinoma and required insertion of inhabiliary Silastic stents for the relief of severe obstructive jaundice. During restaging of her carcinoma for further chemotherapy, she complained of dyspnea, right chest pain and productive cough with yellow sputum. Her chest x-ray film and thoraco-abdominal CT scan demonstrated right pleural effusion with a stent protruding through the right hemidiaphragm. The objective evidence of bile in the pleural aspirate with history of bile-stained sputum established the diagnosis of bronchopleurobiliary fistula resulting from biliary stent migration.
Limiting dilution analysis was used to measure the frequency of PVG-reactive cytotoxic T lymphocytes (CTL) within the peripheral blood mononuclear cell population of Lewis rats before heterotopic transplantation of PVG rat derived cardiac tissue, and in both the blood and graft-infiltrating cell populations at daily time points afterwards. Before surgery, the frequency of PVG-reactive cells within the blood was between 1/31,700 and 1/50,300; however, this value increased rapidly on day 4 after transplantation to reach values of up to 1/1,100 by day 7. The frequency of these cells was first measurable in the graft-infiltrate on day 2 and also showed a rapid increase 4 days after surgery; peak values up to 1/4,800 were recorded on day 5. This time corresponded with that of functional cardiac rejection and maximum infiltration of the graft by mononuclear cells. The similar kinetic changes and absolute values recorded for the frequency of donor-reactive CTL within the blood and graft-derived cell populations was indicative of a rapid bi-directional passage of cells between these pools and provided no evidence for specific sequestration of CTL by the graft. Cells purified from the graft on post-operative day 5 mediated an immediate specific cytotoxicity towards PVG target cells (44% lysis during a 4 h assay at an effector:target ratio of 100:1) which was of a higher activity than would be predicted on the basis of an effector population containing only 1/4,800 PVG-reactive CTL. This finding implies that other mononuclear cell types than CTL present within the graft-infiltrating population were capable of mediating target cells lysis.
Single-lung transplantation in the rat has been shown to provide an effective model for the study of cellular events associated with allograft rejection. It is possible to recover sufficient viable immune cells for functional immunological studies by lavage of the broncho-alveolar space of the grafts with tissue-culture medium. These cells are representative of the population within the parenchymal infiltrate, but are not exposed to harsh, potentially damaging, physical and chemical conditions during their extraction. Lavage-derived cells from non-immunosuppressed recipients showed donor-specific cytotoxicity, were clonable by limiting dilution culture, and proliferated in response to 24-hr stimulation with recombinant IL-2. Administration of Cyclosporin A (CsA) prevented pulmonary rejection and was also shown to block the formation of specific cytotoxic effector cells and the development of responsiveness to IL-2.
Arterial and jugular bulb pressures and blood gas tensions were recorded for later analysis in 65 patients having coronary artery graft surgery. In the first 35 (group A) routine peroperative monitoring was used; and in the next 30 (group B), similar in age and other characteristics, special measures were adopted to maintain normocapnia (PaCO2 35-45 mm Hg) by continuous monitoring during surgery. On the third postoperative day clinical neurological deficits were observed in 46% of group A and 27% of group B, and psychometric deficits in 71% and 40%, respectively. On analysis of the records, more than half of group A proved to have been hypocapnic immediately before onset of cardiopulmonary bypass, and those with postoperative deficits differed from the others in this group in having had greater changes in PaCO2 after onset of bypass and lower cerebral perfusion pressures in the first 10 minutes of bypass, usually because of a rise in cerebral venous pressure.
Sixty-five patients undergoing a thoracic procedure were randomly allocated to one of two groups. The first group received a conventional method of ventilation (double-lumen endobronchial tube and collapse of one lung) and the second, high-frequency jet ventilation (HFJV). The incidence of postoperative chest infections (clinical and bacteriological), the chest drain volumes, and the length of postoperative stay in the hospital were recorded. Results showed the jet ventilator group had a significantly reduced mean hospital stay (p less than 0.01), which could be attributed to a lower incidence of postoperative chest infections (p less than 0.001) and significantly improved arterial blood O2 tensions at 4 hours (p less than 0.05), 24 hours, and 7 days postoperatively (p less than 0.001).
A 54 year old woman with isolated stenosis of the left coronary ostium died following cardiac catheterisation and emergency coronary artery bypass surgery. Histological examination showed the ostial narrowing to be a local and discrete plaque of atherosclerosis. Like most reported cases this patient was a young woman whose disease pursued an aggressive course.
Limiting dilution analysis showed that the frequency of precursor donor-lytic cytolytic lymphocytes increased dramatically within the leucocyte population recovered by broncho-alveolar lavage in dogs after unilateral lung transplantation. The increases for animals experiencing acute pulmonary rejection (11.5-24.8 times pre-operative level) and for those receiving long-term ciclosporin A therapy (5.4-17.6 times pre-operative level) were similar. Therefore, it appears that ciclosporin A does not prevent the sequestration of precursor donor-lytic cytotoxic cells within lung allograft tissue.
Dogs receiving left unilateral allo- or auto-grafts were treated with Cyclosporin A (Cy A) for 4 days. Thereafter allografted transplant recipients showed pulmonary pathology consistent with rejection. Blood and bronchoalveolar lavage (BAL)-derived lymphocytes were isolated from the recipient animals before and at various times after operation and the frequency of allospecific precursor cytolytic lymphocytes (pCTL) determined by limiting dilution analysis (LDA). Samples from the autografted control animal did not show any post-operative frequency changes; however, both blood and BAL-derived lymphocytes from allografted recipients showed a significant post-operative increase in the proportion of donor-specific pCTL. This increase was consistently greater in samples from the transplanted than the autochthonous lung. The frequency of pCTL determined using targets from an unrelated dog showed no post-operative increase. It is likely that the increase in frequency of donor-specific pCTL recorded during graft-rejection is a specific consequence of an interaction between the graft and recipient's immune system.
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The action potential duration (APD) was measured using an Ag-AgCl electrode, in open chest anaesthetised dogs (n = 8) and puppies, 4 to 6 months old (n = 8), with complete atrio-ventricular dissociation and beta-adrenergic blockade. They were paced in the control period at a frequency of 120 beats . min-1. Both adults and puppies showed maximum action potential duration at a test pulse interval of over 700 ms. Below this the adult dogs showed a progressive shortening of the action potential duration (mean APD 81.5% at 200 ms). In contrast, the puppies showed much less shortening (91% at 200 ms; p less than 0.001). Measurements of Na+, K+-ATPase activity by the Rb uptake method gave values of 13.4 +/- 1.3 (puppies, n = 4) and 6.1 +/- 1.1 (adults, n = 6). These results may be consistent with the idea of a greater influx and efflux of sodium in the myocardial cells of the puppy compared with the adult dog.
A retrospective study was carried out of the outcome of 102 patients who underwent a second operation for myocardial revascularisation, necessitated by persistence or recurrence of intractable angina after their first coronary bypass procedures. Operative mortality was 2%. During follow up of the survivors (mean interval 36.4 months) five died, two after further operation, and five underwent further surgery. Sixty eight patients reported an improvement in their symptoms, 57 of whom claimed to have little or no angina. Less favourable results were recorded for those patients reviewed with longer follow up. No useful indicators of prognosis were identified. The problem of angina in patients who have already received bypass grafts is likely to increase as more revascularisation surgery is performed. Reoperation offers a reasonable prospect of helping some of these patients, but not all will be suitable. Their long term prognosis remains uncertain.
Broncho-alveolar lavage was performed on normal and transplanted lungs of dogs that had received unilateral autografts or allografts without immuno-suppression. Differential cell counts were performed on the lavage fluid. Allografts showed a progressive rise in the proportion of neutrophils from the operated lung compared to the unoperated lung. Rejection in the operated lung was subsequently confirmed histologically. Autografted lungs showed no differences in differential cell counts from the unoperated side. Differential cell counts on broncho-alveolar lavage specimens may be useful as an indication of lung allograft rejection.
No definitive method of myocardial preservation has been established and conclusions based on experimental data may not be applicable to patients with coronary artery disease. Fifty patients undergoing coronary bypass grafting were randomly assigned to one of two groups for myocardial preservation. In group A cold cardioplegia with external cardiac cooling was used and in group B ischaemic arrest with mild systemic cooling to 32 degrees C. Myocardial preservation was assessed by analysis of enzymes specific to the heart, left ventricular biopsy, and electrocardiography. Equal protection of the myocardium was provided in both groups but the mean cross-clamp time in group A was significantly longer than in group B. This implies that cardioplegia confers greater protection than intermittent ischaemic arrest.
The ameliorative effect of antiplatelet therapy on atherogenesis of vein grafts was assessed in autologous cephalic veins grafted into femoral arteries of 16 normolipemic and 11 hyperlipemic stump-tailed macaque monkeys. Before grafting, one half of each vein was distended at high pressure (700 mm Hg) and the other half at low pressure (350 mm Hg). Eight normolipemic monkeys were treated with aspirin, 80 mg/day, and dipyridamole, 50 mg/day, and eight were controls. When grafts were harvested at 12 weeks, tissue cholesterol and beta-apoprotein content in grafts from untreated monkeys were significantly higher than in ungrafted, uninjured veins. Antiplatelet therapy eliminated the increase in lipid content of vein segments distended at low pressure, and significantly lowered lipid content of segments distended at high pressure, though not to be control levels of ungrafted veins. Seven of the 11 hyperlipemic monkeys received antiplatelet drugs and four did not. The lipid content of all graft segments was significantly higher than in grafted or ungrafted veins from normolipemic monkeys. Antiplatelet therapy again significantly reduced the lipid content in vein segments distended at both levels of pressure, and also reduced the elevated cholesterol content in ungrafted veins. Although this animal preparation differs in many ways from human coronary bypass operations, these observations may be pertinent to the prevention of atherosclerosis in human vein bypass grafts.
Dobutamine, a new synthetic catecholamine, has been developed as a more specific inotrope and is reported to have less effect on heart rate and peripheral vascular resistance than other catecholamines. Reports of its effects after cardiotomy have cast doubt on this idea. We have compared the haemodynamic effects of dobutamine with isoprenaline (Group I) and with dopamine (Group II) in early postcardiotomy patients. In both groups a dose response curve was evaluated (dopamine and dobutamine were given at 1.25, 2.5, 5.0 and 10.0 microgram/kg/min; isoprenaline at 0.005, 0.01, 0.02 and 0.04 microgram/kg/min). In Group I both drugs caused significant increases in cardiac index at the highest dose level only. At that level isoprenaline was associated with a significantly higher heart rate than dobutamine and a significantly lower systemic vascular resistance. Similarly, in Group II, both drugs caused significant increases in the cardiac index only at the highest dose level. However, the heart rate at this dose was significantly higher with dobutamine. Dopamine caused no changes in heart rate at any dose level. Neither drug was associated with any alteration of systemic vascular resistance. No changes in stroke volume, left atrial pressure or pulmonary vascular resistance were found in either group. The rise in cardiac output was caused mainly by tachycardia.