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Biomedical subjects

W S Walker

Publications and source records attributed to W S Walker.

At least 55 records · Page 3Linked to original sources

Mouse microglial cell lines differing in constitutive and interferon-gamma-inducible antigen-presenting activities for naive and memory CD4+ and CD8+ T cells.

We developed a panel of non-virus transformed cell lines derived from individual microglial precursors residing in the brains of normal mice. These colony stimulating factor-1-dependent cell lines are B7-1+ (CD80), Mac-1+, Mac-2+, Mac-3+, CD45+, MHC class I+, colony stimulating factor-1 receptor+, and they ingest antibody-coated particles. However, the cell lines differ in their expression of B7-2 (CD86), F4/80, Ly-6C and MHC class II molecules. They also differ in their ability to constitutively process and present antigens to naive CD4+ and CD8+ T cells, memory CD4+ and CD8+, and in the manner by which interferon gamma modulates their antigen-presenting activities. These cell lines should be valuable as models for studies on the immunobiology of the microglia.

Adjuvants, Immunologic↗

Use of the Pannell-Milstein roller bottle apparatus to produce high concentrations of the CSF-1, the mouse macrophage growth factor.

A simple roller bottle apparatus for growing B cell hybridomas in dialysis tubing yields high concentrations of monoclonal antibodies (Pannell and Milstein, J. Immunol. Methods (1992) 146, 43-48). Here we describe an adaptation of this apparatus for the simple production of high concentrations of the mouse macrophage specific growth factor, CSF-1. This apparatus appears to have general applicability for the production of other secreted cytokines.

Agar↗

A subset of splenic macrophages process and present native antigen to naive antigen-specific CD4+ T-cells from mice transgenic for an alpha beta T-cell receptor.

The progeny of individual macrophage precursors from mouse spleen were examined for their ability to constitutively process and present native pigeon cytochrome c or a peptide fragment of this antigen to naive CD4+ T-cells from mice transgenic for a V alpha 11/V beta 3 TCR that recognizes an epitope in the antigen fragment. The results show that constitutive Ag processing and presentation is a stable characteristic restricted to the progeny of approximately 20% of splenic macrophage precursors. This property does not appear to be randomly acquired, but to reflect the ability of certain macrophages to produce IL-12.

Animals↗

Potential complications of vascular stapling in thoracoscopic pulmonary resection.

In a series of 57 patients undergoing thoracoscopic pulmonary lobectomy, 2 required expeditious conversion to open thoracotomy when a stapling device (Endo-GIA 30 V3; Autosuture, Ascot, UK) used on the main right lower pulmonary artery in 1 case and on the left superior pulmonary vein in the other cut but failed to staple the vessel involved. In both instances the vessel was successfully controlled while a thoracotomy was performed and the involved vessel was oversewn. Both patients made an uncomplicated postoperative recovery. As the number of thoracoscopic pulmonary resections increases, it is likely that similar episodes will occur in the future. These cases strongly emphasize the fact that patients undergoing this procedure should do so in a center specializing in thoracic surgery where there is the necessary surgical expertise and equipment to deal with such potentially life-threatening vascular complications.

Adenocarcinoma, Bronchiolo-Alveolar↗

Primary small-cell cancer of the esophagus.

Primary small-cell cancer of the esophagus is a rare tumor that disseminates early with a uniformly poor prognosis if untreated. Sixteen patients with malignant dysphagia referred to the Thoracic Surgical Unit, City Hospital, Edinburgh, within a 10-year period had a diagnosis of primary small-cell cancer of the esophagus. Seven patients underwent subtotal esophagectomy or esophagogastrectomy, either alone or with adjuvant chemotherapy or radiotherapy, with a mean survival of 20 months (standard deviation 35.4 months, range 2 weeks to 96 months). The remaining nine patients had disseminated disease when they were first seen and were treated symptomatically by intubation alone (1 patient), intubation and palliative chemotherapy or radiotherapy (3 patients), palliative chemotherapy (2 patients), palliative radiotherapy (1 patient), or no therapy (2 patients), with a mean survival of 4.8 months (standard deviation 2.6 months, range 2 to 9 months). Patients seen with this aggressive tumor should be assessed urgently for evidence of metastatic spread and then offered resection in combination with chemotherapy if they are otherwise fit for operation. This treatment regimen has given us one long-term survivor (96 months) who, we believe, is the only patient to have been cured of this condition. Patients seen with disseminated disease should have symptomatic treatment of the dysphagia combined with palliative chemotherapy.

Carcinoma, Small Cell↗

The Edinburgh Cardiac Surgery Score survival prediction in the long-stay ICU cardiac surgical patient.

Predictors of outcome in long-stay patients following cardiac surgery have hitherto been ill defined. The aims of this study were to test the Parsonnet pre-operative scoring system and to define a scoring system for inhospital mortality applicable post-operatively to strengthen the clinical decision-making process. Following case note review of 262 consecutive patients who stayed 7 days or more in intensive care, a total of 110 pre-, intra- and post-operative factors were documented. In this long-stay group the Parsonnet score was confirmed to be predictive of 30 day mortality. Univariate analysis identified significant association between mortality in the Intensive Care Unit (ICU) and the following: inotrope days, (defined as number of inotropes times number of days) ventilation, units of platelets (P = < 0.00001), chest reopening, fresh frozen plasma units (P < 0.002), total parenteral nutrition, noradrenaline, Parsonnet score (P = 0.005), dopamine, bypass time, vasodilators, intra-aortic balloon counterpulsation, enteral nutrition and other major surgery (P < 0.05). Stepwise logistic regression on these significant factors was used to produce the Edinburgh Cardiac Surgery Score (ECS) applicable from Day 10 onwards in the intensive care unit: ECS Score = (Inotrope days) +2 (Ventilation) + (Platelets) + (Parsonnet) -3. The ECS score may be a useful predictor of ICU mortality probability for cardiac surgical patients requiring 10 days or more intensive care and is presently undergoing prospective evaluation in our centre.

Adult↗

Peroxides in human leucocytes in acute septic shock: a preliminary study of acute phase changes and mortality.

Peroxidation by peripheral blood leucocytes was measured in 15 patients in acute septic shock and 15 uninfected controls, using the probe dichloroflorescein. Mortality in septic subjects was 40%. In 14 of 15 patients from whom serial samples were analysed, periods of increased oxidative activity were detected. Increased peroxidation occurred early in the sequence of clinical changes, at the same time as increases in temperature, blood pressure and C-reactive protein. Peak peroxide production preceded increases in acute phase reactants and changes in leucocyte distribution. Mean peroxide production in leukocytes from patients who died was significantly higher (P < 0.001) than paired controls, and greater (P < 0.05) than peroxide production in patients who survived. The in vitro oxidative response to endotoxin was upregulated in infected patients. This supports the hypothesis that systemic mediators and leucocyte-derived reactive oxygen are involved in the vascular and organ damage associated with fatal septic shock.

Acute-Phase Reaction↗

Initial experience of video assisted thoracoscopic pneumonectomy.

BACKGROUND: Preliminary experience of video assisted thoracoscopic pneumonectomy in six patients with bronchogenic carcinoma is described. METHODS: Four left and two right pneumonectomies were performed under video thoracoscopic imaging. Thoracoscopic instruments were passed through two separate stab incisions on the lateral chest wall and a separate 6 cm submammary incision was also created to allow further access for instrumentation and removal of the resected lung. In this initial experience resection was restricted to patients with bronchogenic carcinomas of less than 6 cm in diameter who had no involvement of the mediastinum. RESULTS: There were no operative deaths and no complications attributable to the technique. One patient developed postoperative atrial fibrillation and a small sacral sore and one patient was readmitted with abdominal pain and pyrexia which settled following exclusion of post pneumonectomy empyema. The remaining four patients made a rapid uncomplicated postoperative recovery with less pain and discomfort than that normally associated with a standard posterolateral thoracotomy. Postoperatively the mean (SD) patient controlled morphine consumption was 1.36 (1.90) mg per hour in the first 36 hours compared with the unit mean for open thoracotomy of 1.73 (1.68) mg per hour. The mean linear visual analogue pain score was 15.4 (15.6) in the first 24 hours compared with the unit mean for open thoracotomy of 34.5 (8.5). CONCLUSIONS: Video assisted thoracoscopic pneumonectomy can be performed safely in patients who have stage I and stage II bronchogenic carcinomas, up to 6 cm in diameter, with no mediastinal involvement on mediastinoscopy and thoracic computed tomographic assessment. This technique may result in less postoperative pain and discomfort and should allow a quicker return to normal activities.

Aged↗

The function of free jejunal autografts in the pharyngo-oesophageal segment.

Eight patients were studied 6 weeks to 16 months following pharyngo-oesophageal reconstruction using a free jejunal interposition graft. Ambulatory manometry was carried out using an intraluminal strain gauge assembly linked to a portable microprocessor. In one patient, the assembly could not be passed because of a redundant jejunal loop. In four subjects, the jejunal interposition appeared to function as a passive conduit with very little manometric activity. In the remaining three patients, however, there was evidence of both propagated peristaltic waves within the graft and regular contractile activity, characteristic of Phase III of the intestinal Migrating Motor Complex (MMC). The presence of MMC activity at only 7 weeks following surgery confirms its independence of extrinsic intestinal innervation. Spontaneous contractile activity, however, was not interrupted by propagated water swallows and may contribute to post-operative dysphagia in some individuals.

Aged↗

Establishment of mononuclear phagocyte cell lines.

Macrophage cell lines have been derived from cells residing in a number of tissues from a variety of species. In this report, the methods used to obtain these cell lines are reviewed and a simple and efficient method for generating nonvirus-transformed lines from individual cloned progenitors located in mouse tissues is described.

Animals↗

The use of bovine internal mammary artery (Bioflow) grafts in coronary artery surgery.

Over a 3-year period 17 patients underwent a total of 25 coronary artery bypass grafts utilising bovine internal mammary artery [BIOFLOW]. Three patients died in the peri-operative or early post-operative period allowing detailed information to be gathered on 14 patients. Seven patients who had had a total of 11 Bioflow grafts implanted underwent post-operative coronary angiography at a mean time of 19 months after surgery revealing occlusion in all the Bioflow grafts. Two patients who underwent aortic valve replacement combined with single Bioflow grafts were symptom-free and refused re-study. Two patients who had three coronary grafts each, including single Bioflow grafts, refused re-study though one of them had recurrent anginal symptoms. Two patients, one with recurrent anginal symptoms, who had a total of four Bioflow grafts were considered unfit for restudy on medical (non-cardiac) grounds. One patient with two Bioflow grafts and recurrent symptoms refused long-term follow-up. Despite reports of good early patency rates with the Bioflow graft, we have not found this to be the case even when patients were anticoagulated post-operatively. We do not recommend the use of this graft as early occlusion is to be expected, which may result in an early return of anginal symptoms.

Aged↗

Efficacy of video assisted thoracoscopic lung biopsy: an historical comparison with open lung biopsy.

BACKGROUND: Video assisted thoracoscopic lung biopsies were compared with historical controls undergoing open lung biopsy to determine the diagnostic accuracy, effect on length of postoperative stay, and cost effectiveness of the new thoracoscopic technique. METHODS: The first 25 video assisted thoracoscopic lung biopsies performed in the Edinburgh Thoracic Unit were compared with 25 historical controls for complications, diagnostic accuracy, and length of postoperative stay. RESULTS: Statistical comparison showed equal diagnostic accuracy in both groups (96% v 92%), but mean (SD) inpatient stay was reduced in the video assisted thoracoscopic group (1.4 (0.7) days) compared with those undergoing open lung biopsy (3.1 (1.8) days). No postoperative complications were reported in the group which underwent video assisted thoracoscopic lung biopsies but three patients had postoperative complications in the open lung biopsy group. CONCLUSIONS: Video assisted thoracoscopic lung biopsy is as effective in providing histological diagnosis as is open lung biopsy. All postoperative complications were related to post thoracotomy pain and occurred only in patients undergoing open lung biopsy. Reduced postoperative disability in the video assisted thoracoscopic group decreased hospital stay, offsetting the increased cost in disposables. The overall cost of video assisted thoracoscopic and open lung biopsy was 712 pounds and 1114 pounds, respectively.

Adult↗

Macrophage progenitors from mouse bone marrow and spleen differ in their expression of the Ly-6C differentiation antigen.

Using mAb and magnetic and fluorescence-activated cell sorting, together with culturing in semisolid culture medium, we show that essentially all splenic macrophage progenitors are Ly-6ChiMac-1-. By contrast, bone marrow macrophage progenitors were more heterogeneous in Ly-6C expression, the majority being restricted to the Ly-6CdimMac-1- and the Ly-6C-Mac-1- subsets. These findings provide immunophenotype evidence that macrophages in the spleen and bone marrow arise from different progenitors.

Animals↗

Alloantigen presentation by individual clones of mouse splenic macrophages. Selective expression of IL-1 alpha in response to CD8+ T cell-derived IFN-gamma defines the alloantigen-presenting phenotype.

Approximately one-third of mouse splenic macrophage (M theta) progenitors yield progeny that constitutively present MHC class I alloantigen to naive T cells, a response that is restricted to CD8+ T cells and is elicited in a CD4+ Th cell-independent manner. In addition, both the alloantigen-presenting (alloAP+) and nonpresenting (alloAP-) M theta subsets constitutively express similar levels of MHC class I molecules, and their alloAP phenotypes are unaffected by IFN-gamma, which enhances the expression of both class I and II MHC molecules. We therefore postulated the restricted expression of costimulator molecules to account for the alloAP+ phenotype. Using cytokine-specific antibodies, recombinant mouse cytokines, and polymerase chain reaction analyses (to detect specific cytokine mRNA transcripts), we identified the putative costimulators as IL-1 alpha, IL-6, and TNF-alpha. TNF-alpha transcripts were present in both the alloAP+ and alloAP- M theta subsets, but IL-1 alpha and IL-6 were not constitutively expressed by the alloAP+ subset of M theta; rather, they were induced by IFN-gamma, which was released from naive CD8+ T cells only during coculture with alloAP+ M theta. Although IFN-gamma induced IL-6 gene transcription in both alloAP+ and alloAP- M theta subsets, it induced IL-1 alpha transcripts only in the alloAP+ subset. Finally, CD8+ T cells exposed to alloAP- M theta were unresponsive when subsequently cultured with alloAP+ M theta. We conclude that the ability of some M theta to elicit IFN-gamma from CD8+ T cells and to respond to this cytokine by producing IL-1 alpha defines the alloAP phenotype of the cell population, and that alloAP- M theta induce a state of alloantigen-specific tolerance in naive CD8+ T cells.

Animals↗

Transaortic division of the mitral subvalvar apparatus.

Adequate exposure of the mitral valve can be difficult to obtain through a median sternotomy. A variety of techniques have been described to facilitate exposure in this situation. This report describes the use of trans-aortic technique which allows easy and accurate division of the mitral subvalvar apparatus. The mitral valve can then be approached through a left atriotomy, everted and the excision completed.

Aorta↗

Synchronous primary lung cancers: prevalence in surgical material and clinical implications.

BACKGROUND: The prevalence of synchronous primary lung neoplasms in surgical resection specimens was assessed. The associated clinical features and prognostic implications were investigated. METHODS: All surgical resections for lung cancer performed during seven years were reviewed. Synchronous tumours were defined by the presence of more than one tumour mass in the lung, by differences in histological subtype, by the presence of separate bronchial origins, or by differences in DNA stemlines. Clinical data were abstracted from case notes and information from the tumour registry. RESULTS: Just under 2% of all surgical specimens in the study period contained more than one primary carcinoma. The patients did not differ clinically from the general population of patients having surgery for lung cancer. The overall prognosis was poor (mean survival 27 months) but was significantly better for patients with synchronous squamous carcinomas (mean survival 49 months). CONCLUSION: Synchronous primary lung carcinomas are associated with a poor prognosis except in patients having tumours only of squamous histological type.

Adenocarcinoma↗