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Biomedical subjects

M J Wilkinson

Publications and source records attributed to M J Wilkinson.

67 records · Page 4Linked to original sources

Bactericidal effects of amoxycillin/clavulanic acid against intracellular Legionella pneumophila in tissue culture studies.

The bactericidal effects of amoxycillin, clavulanic acid and amoxycillin plus clavulanic acid were determined against Legionella pneumophila growing intracellularly in MRC-5 human fetal lung fibroblast cells. The strain of L. pneumophila was shown to be growing within the cells by transmission electron microscopy and this was confirmed by the results of bactericidal tests in which gentamicin was shown to be ineffective in preventing growth of the organism in the tissue culture system. Amoxycillin failed to prevent infection of the cell monolayers and had no effect on the growth of intracellular L. pneumophila. Transmission electron microscopy showed the presence of large numbers of bacteria of normal morphology within the fibroblasts. In contrast, clavulanic acid and amoxycillin/clavulanic acid protected the cell sheets from the effects of infection with L. pneumophila and reduced the numbers of intracellular bacteria to the same extent as erythromycin. Also, bacteria of abnormal morphology were observed within fibroblast cells of the cultures treated with clavulanic acid and the combination. These data demonstrate the penetration of clavulanic acid, when used alone or in the presence of amoxycillin, into cells infected with L. pneumophila and the resulting bactericidal activity of the agents against intracellular bacteria.

Amoxicillin↗

Psychiatric screening in general practice: comparison of the general health questionnaire and the hospital anxiety depression scale.

The prevalence of psychiatric disorder in 100 patients attending their general practitioner was found to be 33% based on the criteria of the DSM-3 diagnostic system. Using the DSM-3 diagnosis as a yardstick, the performance of the hospital anxiety depression scale was compared with that of the general health questionnaire. Relative operating coefficient analysis showed good discrimination between ;cases' and ;non-cases' for both questionnaires, and the optimum threshold score was found to be eight for the hospital anxiety depression scale and five for the general health questionnaire. Using these threshold scores the positive predictive value was 81% for the hospital anxiety depression scale and 77% for the general health questionnaire. The hospital anxiety depression scale appeared more sensitive than the general health questionnaire (90% versus 77%) and simpler to complete. In addition, it does not require a different threshold score for each population studied. The use of screening questionnaires in general practice is discussed.

Adult↗

Endocrine therapy for advanced carcinoma of the breast: relationship between the effect of tamoxifen upon concentrations of progesterone receptor and subsequent response to treatment.

In some cell lines and tumors of mammary origin, tamoxifen causes an increase of progesterone receptor (PR) as a result of its partial estrogen agonist activity. In this study we have assessed the effect of tamoxifen on PR in patients with advanced carcinoma of the breast in order to test if those with a rise in PR are more likely to respond to endocrine therapy. PR was measured before and a median of 13 days after treatment with tamoxifen in a group of 52 patients with either locally advanced (n = 28) or recurrent (n = 24) carcinoma of the breast. Controls were a group of patients with operable disease who had two biopsies with no intervening tamoxifen (n = 51) or with intervening tamoxifen (n = 58). In the test group PR was higher in the second biopsy than the first in 21 patients, and 19 of these responded to continued endocrine therapy (90%). In the remaining 31 patients PR was either lower in the second biopsy (n = 19) or was negative in both biopsies (n = 12), and 11 of the total of 31 patients (35%) responded to continued endocrine therapy. The prediction of response and time to progression was better when both biopsies were taken into account than either the first or the second alone. The prediction of survival was similar for the group selected by an increase in the second biopsy and the group with PR present in the second biopsy. The controls without tamoxifen showed a marked variation in the level of PR in the first and second biopsies, suggesting heterogeneity of PR across the tumors studied. However, the PR level was significantly higher in the second biopsy in the controls given tamoxifen and in the test group compared with those with no intervening treatment (p = 0.031). This study indicates that some effect of tamoxifen upon PR can be demonstrated in human mammary tumors in vivo and that, by taking a second biopsy for PR estimation during treatment with tamoxifen, a more precise indication of subsequent response is obtained. The value of a single estimation of PR before treatment on secondary deposits is limited, and if one biopsy only is performed, it is of greater predictive value if taken after a few days treatment with tamoxifen.

Aged↗

Tissue arrangement in the internal elastic lamina of the rat muscular pulmonary artery.

The arrangement of tissue in the internal elastic lamina of muscular pulmonary arteries in rats has been studied. It consists of long plates of elastic tissue joined to each other by side branches, thus forming a continuous branching network. The thick plates are orientated parallel to the long axis of the vessel. This is similar to the arrangement in the saphenous and splenic veins in the dog. Systemic arteries show a different arrangement, usually a single fenestrated sheet. The differences between systemic and pulmonary arteries can be explained by considering the different biomechanical forces acting on them.

Animals↗

The foreign body reaction in total hip arthroplasties. A correlated light-microscopy, SEM, and TEM study.

An in vivo histological and ultrastructural study of the cellular reaction to particulate material currently used in orthopaedic surgery produced evidence that, on a strictly cellular level, the main damage is done by the smallest particles produced by hip prostheses, i.e. metal particles, irrespective of differences in their chemical composition. Particle size and release rate are the critical factors, although other mechanisms of cellular damage may be active once granulation tissue is formed.

Chromium Alloys↗

Retroperitoneal tumour infiltration detected by bone scanning in patients with infiltrating lobular carcinoma of the breast.

Radionuclide bone scans performed in some patients with carcinoma of the breast showed abnormal retention of isotope in the renal pelvis which developed and progressed during the period of follow-up after mastectomy. This phenomenon was seen in 15 of 30 patients with infiltrating carcinoma of the breast (ILC) but in none of 29 with infiltrating duct carcinoma (IDC). Autopsies were performed in eight of the patients with ILC and three of those with IDC. Diffuse retroperitoneal and ureteric infiltration was seen in seven (88 per cent), with ILC and none with IDC. These data suggest that this scan abnormality is an indicator of retroperitoneal spread by ILC.

Bone Neoplasms↗

Involvement of metal particles in loosening of metal-plastic total hip prostheses.

Four loosened metal-on-plastic total hip prostheses and associated tissues were examined. Each implant showed an uncommonly high formation of metal particles produced by wear or corrosion of the femoral stem. The granulation tissue between bone and cement was characterized by macrophages containing metal particles. Histological, histochemical, and ultrastructural investigations have been performed to assess cellular reactions to ingested metal particles. Pathogenesis of loosening in these cases is discussed in relation to the role of macrophages in bone resorption.

Aged↗

Steroid-hormone receptors and survival after first relapse in breast cancer.

Oestrogen receptors were measured in the primary breast tumours of 508 patients and progesterone receptors in those of 486 patients. Survival from mastectomy was significantly longer in patients with receptor-positive tumours. There was no significant difference between patients with receptor-positive and receptor-negative tumours in the relapse-free interval, but survival from first relapse was longer in patients with receptor-positive tumours. Axillary node status and tumour size indicated the probability of relapse but did not influence the length of survival after relapse. Response to tamoxifen or ovarian ablation was known in 65 of the 137 patients who relapsed. Survival from first relapse was significantly longer in patients who both responded to hormone therapy and had receptor-positive tumours. Patients who did not respond to hormone therapy and had receptor-positive tumours had the same survival characteristics as those with receptor-negative tumours who did not respond.

Breast Neoplasms↗

The prognostic significance of two epithelial membrane antigens expressed by human mammary carcinomas.

As many patients with mammary carcinoma are now treated by conservative forms of surgery, there is a need for prognostic information obtainable from the primary tumour alone. One possible source is the antigenic profile of tumour cells. Using an indirect immunoperoxidase technique, we stained histological sections of the primary tumour from 175 patients with each of two monoclonal antibodies (HMFG-1, HMFG-2), raised against milk fat globule membrane antigens known to be preserved in formalin-fixed tissues. Sections were assessed by light microscopy as to both the overall distribution of antigen expressed and its site in tumour cells. The findings were related to relapse-free survival by life-table analysis. The median duration of follow-up was 36 months. Two patterns of staining with antibody HMFG-1 gave information of prognostic significance but staining with HMFG-2 was without significance. Complete absence of staining with HMFG-1 in 13 patients was associated with an extremely poor prognosis and 10 (77%) of these patients developed metastases within 18 months of follow-up (p less than 0.001). Extracellular staining (ECS) in 22 patients, however, was associated with a favourable prognosis. As assessed by a semi-quantitative method, only one patient (5%) demonstrating a high level of ECS developed metastases (p less than 0,004). These two patterns were analysed for a relationship to other prognostic indicators. Absence of staining was independent of histological grade, tumour size, axillary lymph node status and menopausal status. ECS was associated with low histological grade although this relationship was not absolute. In addition to their use in diagnosis, we conclude that monoclonal antibodies such as HMFG-1 may be useful as prognostic indicators.

Antibodies, Monoclonal↗

Native and inducible levels of natural cytotoxicity in lymph nodes draining mammary carcinoma.

Lymphocytes isolated from axillary nodes draining breast carcinoma possess variable natural cytotoxic capacity. Augmentation of lymph node cell (LNC) cytotoxicity by interferon (IFN) is also variable, with only some populations displaying potentiated lysis following exposure to either IFN-a or gene-cloned IFN-a2. Where present the IFN-induced augmentation of LNC cytotoxicity was invariably weaker than that observed following similar treatment of autochthonous peripheral blood mononuclear cells (PBMC). Irrespective of their responsiveness to IFN the cytotoxic activity of all LNC preparations examined was significantly increased following pre-incubation with either staphylococcal enterotoxin A (SEA) or factors elaborated by lectin-pulsed allogeneic LNC. THe induction or amplification fo LNC-mediated natural cytotoxicity by lymphokines may provide a local potentiation of natural immune function at the host : tumour interface.

Breast Neoplasms↗

Plasma membrane ultrastructure during plant protoplast plasmolysis, isolation and wall regeneration: a freeze-fracture study.

The freeze-fracture morphology of the plasma membrane of cells and isolated protoplasts of plant callus suspensions has been investigated. Plasmolysis of suspension cells leads to the formation of 2 types of hexagonal arrays of intramembrane particles situated on the inner fracture face (PF). These arrays are interpreted as proteins that have 'crystallized' in the plane of the membrane as the area of surrounding lipid bilayer is reduced during protoplast retraction from the cell wall. Time-course studies have revealed no positive relationship between the distribution of hexagonal arrays and the occurrence of microfibrils regenerated around isolated protoplasts during periods of culture. No evidence for the specialized transport functions attributed to hexagonal arrays of plant cells by previous workers has been found.

Cell Membrane↗