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Biomedical subjects

W S Walker

Publications and source records attributed to W S Walker.

At least 73 records · Page 4Linked to original sources

Thoracoscopy assisted pulmonary lobectomy.

BACKGROUND: This report describes a preliminary experience with six patients undergoing video imaged thoracoscopic pulmonary lobectomy. METHODS: Three left upper lobectomies, and one each of right upper, right lower and left lower lobectomy were undertaken. The resections were performed as orthodox dissectional lobectomy procedures but were carried out under videothoracoscopic imaging with instruments introduced through two stab incisions. The entire resected lobe was delivered through a 7 cm submammary intercostal incision. RESULTS: There were no operative deaths or complications attributable to the technique. In three other patients conversion to an open thoracotomy was required because of bleeding (two cases) or obscure anatomy (one case). Post-operative pain in those undergoing thoracoscopic resection was less than that encountered with standard thoracotomy and early clinic review showed the patients to be pain free with excellent shoulder movement. CONCLUSIONS: Major pulmonary resection according to standard cancer practices is feasible with videothoracoscopic techniques. This approach is likely to offer considerable functional benefit to patients. Specimen delivery through the submammary incision imposes a 5 cm primary lesion size limitation. Detailed mediastinal assessment is necessary to exclude N2 status before undertaking thoracoscopic surgery.

Aged↗

Thoracoscopic pulmonary lobectomy. Early operative experience and preliminary clinical results.

Thoracoscopic video-assisted lobectomy procedures were performed in 11 patients (7 men, 4 women; age range 40 to 74 years, mean 66 years). Ten patients had peripheral pulmonary opacities: eight of these were bronchogenic carcinomas, one was an atypical carcinoid lesion, and one was a pulmonary infarct. All of these cases had preoperative evaluation by computed tomographic scanning to exclude mediastinal lymphadenopathy. The remaining patient had preoperatively diagnosed lobar bronchiectasis. Surgical access was gained via three stab (1 cm) incisions and one short (7 cm) submammary incision, which was made without rib separation and was used for specimen delivery. Lobes resected were the left upper (n = 4), left lower (n = 2), right upper (n = 2), and right lower (n = 3). All patients survived. Overall mean operative time was 3.3 hours and blood loss 263 ml. For the latter five cases, however, these figures were reduced to 2.3 hours and 100 ml, respectively, indicating improvement with experience. In no cases was ventilatory assistance required. Mean high-dependency unit time was 41 hours. In each case, it was possible to perform a standard dissectional lobectomy with lobar lymph node clearance equal to that obtained at open thoracotomy. Comparison with a series of 33 open lobectomy procedures demonstrated reduced postoperative pain, morphine consumption, and high-dependency unit stay. This preliminary experience supports the development of video-assisted thoracoscopic pulmonary lobectomy for patients with small peripheral opacities or known benign disease.

Adenocarcinoma↗

Mouse macrophages contain a truncated CD4 transcript.

Mouse macrophages do not express CD4 on their surfaces. We used the polymerase chain reaction to investigate CD4 gene transcription in individual clones of primary mouse splenic macrophages and cell lines of spleen and bone marrow macrophages. The results show only the presence of CD4 mRNA transcripts that are truncated in the 3' coding sequence, thus explaining the lack of expression of a mature CD4 gene product by these cells.

Animals↗

Mouse splenic macrophage cell lines with different antigen-presenting activities for CD4+ helper T cell subsets and allogeneic CD8+ T cells.

A panel of seven mouse splenic macrophage cell lines, derived from cloned progenitors, was compared for their ability to present antigen to Th1 or Th2 helper T cell lines and hybridomas, as well as to naive T cells, and to provide accessory cell function for the synthesis of antibody from primed B cells. One of the cell lines expressed MHC class II molecules and was the only line with constitutive antigen-presenting activity for Th1 cells. It may represent a subset of splenic macrophages responsible for the activation of naive Th1 helper cells in situ. The remaining six cell lines responded to INF-gamma by up-regulating their class II expression and acquiring Th1 antigen-presenting activity. They may represent cells which, in situ, lack constitutive antigen-presenting activity but are promoted to presenting status by Th1-derived INF-gamma. Five of the cell lines provided accessory cell function to Th2 cells, as indicated by antibody synthesis in suspensions of spleen cells from primed mice depleted of their antigen-presenting cells. One of the cell lines lacking accessory cell activity had constitutive antigen-presenting activity for Th1 cells. This reciprocal expression of antigen-presenting activity supports the idea that Th1 and Th2 helper cells are activated by different antigen-presenting cells. Finally, the cell lines differed in their ability to constitutively induce an allogeneic response; a response that was limited to CD8+ T cells occurred in a CD4+ helper cell-independent manner and was unaffected by the addition of INF-gamma. The alloantigen-presenting macrophage cell lines also possessed the most efficient accessory cell activity for antibody synthesis. These cell lines, which represent a spectrum of antigen-presenting activities in the spleen afford models for defining the roles of macrophages in the induction of immune responses and for resolving issues concerning their development.

Animals↗

Isolated sternal fracture: a benign injury?

Since seat belt legislation was introduced in this country in 1983, we have seen an increasing number of patients admitted to our unit for observation following seat belt related sternal fractures. In order to determine the value of routine admission of patients with isolated sternal fracture we have reviewed a series of 104 consecutive patients admitted between February 1983 and February 1990 with this injury. Of these, 90 were sustained in road accidents, 79 of which were as a consequence of seat belt use. The average age of these patients was 54.5 years (range 11-85 years) with an average duration of hospital stay of 2.9 nights. No serious complications were observed. These findings suggest that there may be no need to admit these patients solely for observation if their initial clinical condition is satisfactory and there are no abnormalities identified by an anteroposterior chest radiograph and electrocardiography.

Accidents, Traffic↗

Phenotypes and alloantigen-presenting activity of individual clones of microglia derived from the mouse brain.

To clarify the origin and function of the microglia residing in the central nervous system, we cloned brain cells from newborn and adult mice in soft agar containing the macrophage-specific growth factor, colony-stimulating factor-1 and expanded the cells from individual colonies in liquid culture medium. The results of molecular, immunophenotypic and functional analyses showed that the clones consisted of microglia derived from the macrophage family of cells. For instance, the microglia contain mRNA transcripts for the receptor for colony-stimulating factor-1 and truncated CD4 transcripts similar to those found in mouse macrophages but not T helper cells. About a third of the microglial progenitors gave rise to progeny that constitutively induced the selective proliferation of naive allogeneic CD8+ T cells in a CD4+ T cell-independent manner, a response that was inhibited by monoclonal antibodies to major histocompatibility complex (MHC) class I molecules on the microglia. Since all microglia expressed similar levels of MHC class I molecules, the basis for the alloantigen presentation likely resides in the ability of some clones of microglia to synthesize co-stimulator molecules that are required for CD8+ T cell proliferation. Thus, at least some microglia in mouse brain arise from endogenous progenitors and appear capable of specialized functions.

Animals↗

A controlled trial of intra-operative autologous transfusion in cardiothoracic surgery measuring effect on transfusion requirements and clinical outcome.

We carried out a prospective, controlled trial of intra-operative autologous transfusion (IOAT) in cardiac surgery using the Haemonetics Cellsaver 4, to determine the effects on transfusion requirements and early clinical outcome. Intra-operative autologous transfusion in unselected patients resulted in a reduction in the use of red cells in patients undergoing first-time operations (IOAT median 3 units, controls median 4 units, P = 0.0023), with no difference in the use of other blood products. Post-operative haemoglobin was higher in IOAT patients (IOAT 11.6 g/dl +/- 1.1 versus controls 11.2 g/dl +/- 0.98, P < 0.001). There is therefore the potential for a further reduction in homologous blood use in the IOAT group. There was no difference in early clinical outcome in the two groups; in particular the incidence of coagulopathies was not influenced by IOAT. The routine use of IOAT would add substantially to the cost of these operations. The decision to use it must therefore be based on an assessment of the value of the reduction in risk to the patient achieved by a small reduction in homologous donor exposures.

Adult↗

Pathological assessment of mediastinal lymph nodes in lung cancer: implications for non-invasive mediastinal staging.

BACKGROUND: The use of computed tomography in mediastinal staging of lung cancer relies on the premiss that malignant lymph nodes are larger than benign ones. This hypothesis was tested by linking node size and presence or absence of malignancy and looking at factors possibly influencing the size of benign nodes. METHODS: All accessible mediastinal lymph nodes were taken from 56 consecutive patients with lung cancer who underwent thoracotomy. Nodes were measured and histologically examined. Resected cancer bearing lung from 44 of these patients was assessed for degree of acute and chronic inflammation. RESULTS: Lymph node size was not significantly related to the presence of metastatic disease, 58% of malignant and 43% of benign lymph nodes measuring over 15 mm. Similarly, there was no statistically significant relation between size of lymph nodes and the likelihood of malignancy, 20% of lymph nodes of 10 mm or more but also 15% of those less than 10 mm being malignant. Thresholds of 15 and 20 mm showed similar results. The maximum size of benign lymph nodes was significantly greater in those patients with histological evidence of acute pulmonary inflammation than in those without. CONCLUSIONS: The study shows that in patients with lung cancer (1) malignant mediastinal lymph nodes are not larger than benign nodes; (2) small mediastinal lymph nodes are not infrequently malignant; and (3) benign adenopathy is more common in patients with acute pulmonary inflammation.

Adenocarcinoma↗

Prognostic significance of tumor deoxyribonucleic acid content in surgically resected small-cell carcinoma of lung.

The prognostic role of deoxyribonucleic acid flow cytometry was investigated in 53 cases of surgically resected small-cell lung cancer. Deoxyribonucleic acid aneuploidy was detected in 26 patients (49.1%), the remaining tumors being either diploid or tetraploid. Patients with aneuploid tumors had a significantly reduced 2-year survival (38.5%) when compared with patients with diploid or tetraploid tumors (70.3%; p less than 0.05). This finding was independent of tumor stage on multiple logistic regression analysis. Diploid or tetraploid deoxyribonucleic acid content was associated with a particularly good 2-year survival (85%) in N0 or N1 disease. Tumor deoxyribonucleic acid ploidy should be taken into account in planning of management and assessment of prognosis in small-cell lung cancer.

Carcinoma, Small Cell↗

Management of chylothorax complicating extensive esophageal resection.

Between January 1983 and May 1987, 255 esophagectomies were performed for carcinoma of the middle (40 patients) or lower (215 patients) esophagus. All patients were operated upon through a left thoracolaparotomy and underwent a radical en bloc resection of the tumor along with all palpable mediastinal nodes. Ten patients had chylothorax develop postoperatively. There were seven men and three women with a mean age of 65.7 years (range of 37.0 to 81.0 years). Parameters that were statistically evaluated for possible correlation to increased incidence of chylous fistula were age, sex, site and size of tumor, histologic type, mediastinal lymphatic involvement and elective prophylactic ligation of the major thoracic duct (MTD) at the conclusion of the procedure. It was found that elective ligation of the MTD was associated with a lower occurrence of chylothorax (2.1 per cent) as compared with those with no routine ligation (9 per cent), p less than 0.05. The leak was successfully treated by repeated thoracotomy and mass ligation of the MTD in eight patients, while one patient underwent closed tube thoracostomy. In one instance, only a pleuroperitoneal shunt was performed. The over-all hospital mortality rate from chylothorax was 10 per cent and there was a late death because of pneumonia. We recommend prophylactic ligation of the MTD in all instances of extensive esophageal resection for the prevention of chylothorax, as well as early thoracotomy for the management of established leaks.

Aged↗

A subset of mouse splenic macrophages can constitutively present alloantigen directly to CD8+ T cells.

About a third of mouse splenic macrophage (M phi) progenitors give rise to cloned progeny that constitutively induce the selective proliferation of naive allogeneic CD8+ T cells in a CD4+ helper cell-independent manner--a response that is inhibited by mAb to the MHC class I molecules present on the M phi. Colony-mixing experiments indicated that the failure of most M phi clones to present allo-Ag was not due to their suppression of the ability of CD8+ cells to respond, nor did the nonpresenting clones interfere with the activity of the allo-Ag presenting M phi. The allo-Ag presenting phenotypes were found to be a stable characteristic in a panel of cell lines derived from individual clones of M phi. Analysis of the cell lines revealed that the differential expression of allo-APC activity could not be attributed to the levels of MHC class I molecules; rather, the cell lines and the primary M phi clones differ in their expression of a cell-associated costimulator molecule that likely functions to induce the expression of the IL-2R on and the secretion of IL-2 from the T cells.

Animals↗

Constitutive antigen presentation by mouse splenic macrophages is restricted to the progeny of a distinct progenitor population.

Mouse splenic macrophage progenitors differ in their ability to give rise to cloned progeny that constitutively present complex protein antigens to T-cell hybridomas. To determine if the constitutive presentation of diverse antigens is restricted to cells derived from the same subpopulation of progenitors, we expanded macrophage clones into multiple subcultures and compared them for the ability to present different antigens to their respective antigen-specific T-cell hybridomas. Only subcultures derived from the same minority fraction of splenic macrophage progenitors were capable of constitutively presenting the antigens, and the activity of these subcultures was unaffected by the addition of recombinant murine IFN-gamma. This suggests that a specialized sub-population of constitutive antigen-presenting macrophages exists in the spleens of mice.

Animals↗

Immortalization of growth factor-dependent mouse splenic macrophages derived from cloned progenitors.

We describe a nonviral transformation strategy for the establishment of permanent cell lines derived from the progeny of individual mouse splenic macrophage (M phi) progenitors. These colony stimulating factor-1 (CSF-1)-dependent cell lines possess many features of mature M phi s, including antibody-dependent phagocytic and cellular cytotoxic activities, ability to secrete lysozyme, and expression of the Mac-1 antigen and mRNA for the CSF-1 receptor. It was also possible to immortalize selected clones of splenic M phi s differing in their constitutive antigen-presenting activities with the retention of the antigen-presenting phenotype in the resultant cell lines. The approach described in this report should be useful in obtaining additional cell lines of M phi s expressing other phenotypes of interest.

Animals↗

Characterization of effector functions of v-raf/mil- and v-myc-transformed murine splenic macrophage cell lines.

We have characterized several of the cytocidal effector functions of a series of cell lines derived by recombinant retroviral transformation of individual clones of C3H/HeJ mouse splenic macrophages. The three cell lines described in this report (4.01, 4.07, 4.14) all expressed equivalent tumoricidal activity against P815 tumor target cells. However they differed in their high avidity binding of tumor cells (4.01 = 4.14 greater than 4.07), as well as in the killing of Leishmania major (4.01 = 4.07 greater than 4.14), the expression of antibody-dependent cellular cytotoxicity against chicken erythrocytes (4.14 greater than 4.01 greater than 4.07), and finally, in the tumor-stimulated release of tumor necrosis factor-alpha (4.01 = 4.14 greater than 4.07). The stable and restricted expression of distinct effector functions among these three cell lines makes them particularly valuable as models for establishing the precise mechanisms by which cytocidal functions are effected. In addition, they should also prove of value in understanding the basis for macrophage functional diversity.

Animals↗

Influence of obesity on the early and long term results of surgery for coronary artery disease.

In order to determine the effect of obesity on the results of coronary artery bypass graft (CABG) surgery, we compared 250 obese patients undergoing CABG procedures between 1984 and 1987 with 250 age- and sex-matched controls of normal body mass index (BMI) undergoing CABG in the same period. The obese group had a greater incidence of diabetes mellitus (p less than 0.02), hypertension (p less than 0.05), hyperlipidaemia (p less than 0.05), and left main stem coronary artery disease (p less than 0.001). No differences were identified in the surgery performed, but obesity was associated with prolonged total bypass time (p less than 0.05). Operative mortality was 0.8% in both groups. Multivariate analysis demonstrated obesity to be an independent risk factor for perioperative morbidity (p less than 0.05). Univariate: respiratory (p less than 0.01); leg wound (p less than 0.001); myocardial infarction (p less than 0.02); arrhythmias (p less than 0.02); sternal dehiscence (p less than 0.02). At a mean follow-up time of 36.9 months obese patients exhibited a greater incidence of significant recurrent angina (p less than 0.01), which was associated with further weight gain (mean 12.2 kg; linear correlation: p less than 0.001, r = 0.891). Although in CABG surgery operative mortality is not increased in obese patients, aggressive pre- and postoperative weight control is indicated to reduce both perioperative morbidity and the incidence of recurrent angina.

Angina Pectoris↗

T tube intubation in the management of seriously ill patients with oesophagopleural fistulae.

Ten patients referred late with oesophagopleural fistulae were managed by T tube intubation of the oesophageal defect. Seven survived and six had radiographic evidence of closure of the defect. One patient who removed his T tube early was discharged to convalesce with a small oesophagocutaneous fistula. Three patients died as a consequence of pre-existing renal failure, upper gastrointestinal haemorrhage and adult respiratory distress syndrome. Patients presenting late with multisystem complications and ongoing sepsis secondary to oesophagopleural fistulae pose a major management problem. Our preliminary results suggest that T tube intubation offers a potential alternative to major surgical intervention, when more conservative measures have failed.

Acute Kidney Injury↗