Search PubMed⌕ Search

Biomedical subjects

R E Mansel

Publications and source records attributed to R E Mansel.

At least 73 records · Page 4Linked to original sources
PubMed1998

Power Doppler in breast tumours: a comparison with conventional colour Doppler imaging.

OBJECTIVE: Tumour vascularity can be assessed in-vivo using Doppler ultrasound. The purpose of this study was to determine whether Power Doppler imaging (PDI) better differentiates benign from malignant breast masses than conventional colour doppler imaging (CDI) on the basis of assessment of tumour vascularity. METHODS: One-hundred women with solid breast lumps (51 malignant lesions, 49 benign lesions) were investigated using a Toshiba SSA-270A ultrasound machine with a 5.0 MHz (3.75 MHz Doppler reference frequency) or a 7. 5 MHz (5.0 MHz Doppler reference frequency) linear array probe. The vascularity within or at the periphery of the mass was subjectively assessed from the CDI and Power Doppler images by two independent observers. It was assumed that the absence of vascularity indicated benignity and the presence of flow malignancy. RESULTS: CDI showed sensitivities of 62 and 42% and specificities of 62 and 62% using the 5 and 7.5 MHz probes respectively. PDI showed sensitivities of 76 and 51% and specificities of 56 and 48% using the 5 and 7.5 MHz probes respectively. A comparison of images of the 59 lesions investigated with both probes on both CDI and PDI concluded that the 5 MHz (3.75 MHz DRF) probe displayed equal vascularity to the 7.5 MHz (5.0 MHz DRF) probe in 76% of cases and greater vascularity in 24% of cases on CDI, and 68 and 31% of cases respectively on PDI. CONCLUSION: Power Doppler imaging with a 5 MHz (3.75 MHz DRF) probe increases the sensitivity of Doppler ultrasound to malignant breast tumours but the sensitivity achieved is not high enough to propose it as a screening investigation.

Adult↗
PubMed1998

Eicosatrienoic acid (20:3 n-9) inhibits the expression of E-cadherin and desmoglein in human squamous cell carcinoma in vitro.

Eicosatrienoic acid (ETA 5,8,11, n-9) is abnormally increased by essential fatty acid deficiency (EFAD), a condition associated with alterations of cell proliferation and differentiation. In comparison to certain EFAs, addition of ETA at a low concentration resulted in a reduction in the expression of the cell-cell adhesion molecule, E-cadherin, and to a lesser degree, of desmoglein, along with increased invasion of Matrigel by human squamous cell carcinoma (SCC) cells in vitro. At higher concentrations, ETA stimulated the growth of SCC cells. As previously shown, n-6 EFAs (mainly 18:3 n-6, GLA), up-regulated the expression of E-cadherin and desmoglein. This is the first report showing that the abnormal 20:3 n-9 (Mead's acid) is a down regulator of antimetastatic E-cadherin and desmoglein expression.

8,11,14-Eicosatrienoic Acid↗
PubMed1998

The effects of n-6 polyunsaturated fatty acids on the expression of nm-23 in human cancer cells.

This study examined the effect of n-6 polyunsaturated fatty acids (PUFAs) on the expression of nm-23, a metastasis-suppressor gene, in two highly invasive human cancer cell lines, HT115 and MDA MB 231. A range of n-6 and n-3 PUFAs were tested. We report that while linoleic acid and arachidonic acid reduced the expression of nm-23-H1, gamma linolenic acid (GLA) and its soluble lithium salt markedly increased the expression of the molecules. The stimulation of the expression of nm-23 by GLA was seen at both protein and mRNA levels. Up-regulation of nm-23 was also associated with a reduction of the in vitro invasiveness of these cells. It is concluded that gamma linolenic acid (GLA) enhances the expression of nm-23. This contributes to the inhibition of the in vitro invasion of tumour cells.

Arachidonic Acid↗
PubMed1998

The long-term course of mastalgia.

Mastalgia is a common condition in women of reproductive years. We have assessed the long-term course in patients with severe mastalgia by distributing a postal questionnaire to 212 patients previously studied in 1983 who had attended the mastalgia clinic at the University Hospital of Wales, Cardiff. 175 patients (83%) responded, with an original diagnosis of cyclical mastalgia (CM) in 120 and non-cyclical mastalgia (NCM) in 55. The median age of onset of breast pain was 36 years (range 12-63 years). The average duration of pain was long (median 12 years), especially if it started in the second or third decade of life. Pain persisted in 68 (57%) of CM and 35 (64%) of NCM patients. In CM patients resolution was commonly associated with a 'hormonal' event, notably the menopause; in NCM patients it more often seemed to be spontaneous. Severe mastalgia ran a chronic relapsing course often requiring repeated drug treatments.

Adolescent↗
PubMed1998

gamma-Linolenic acid blocks cell cycle progression by regulating phosphorylation of p27kip1 and p57kip2 and their interactions with other cycle regulators in cancer cells.

gamma-Linolenic acid (gamma-LA), a n-6 essential fatty acid, has been previously shown to affect cell cycle and growth of cancer cells. This study examined the effects of gamma-LA on the cell cycle and cycle regulators in human colon cancer HT115 and breast cancer MCF7 cells. Brief treatment of cancer cells (<2 h) with gamma-LA resulted in a decrease in the phosphorylation of both cell cycle inhibitors, p27kip1 and p57kip2 as shown by immunoprecipitation and Western blotting. Protein levels of both inhibitors were increased following a prolonged culture of cells with the fatty acid. A co-precipitation study showed that in cells treated with gamma-LA there was an increase in the binding of these inhibitors with CDK4, CDC2, and cyclin E. Flow cytometry study indicated an inhibition of cell cycle progression by gamma-LA (G0/G1 -45.4%, S - 34.6%, G2+M - 20.0% in control, and 70.5%, 21.0%, and 8.5%, respectively, in gamma-LA treated cells). It is concluded that gamma-linolenic acid inhibits cell cycle progression in the cancer cell lines investigated, via its regulation of the phosphorylation and subsequent degradation of p27kip1 and p57kip2 and their interactions with other cycle regulators.

Breast Neoplasms↗
PubMed1998

European guidelines for quality assurance in the surgical management of mammographically detected lesions. European Breast Cancer Working Group.

The European Guidelines developed for mammography screening have contributed to the general discussion on quality assurance and the important tasks of the health professionals dealing with breast cancer screening. The cooperation of each medical discipline is of utmost importance in order to achieve optimal results and eventually a mortality reduction. The following guidelines are based on the British NHS quality assurance guidelines for surgeons in breast cancer screening and modified to meet the different needs in the European Countries. The term "surgeon" denotes a medical doctor trained and involved in the surgical treatment of breast diseases. The members of the working group who participated in order to adapt these guidelines are listed above. We hope that this document will contribute towards a more comprehensive approach of breast cancer screening-detected lesions throughout Europe.

Breast Neoplasms↗
PubMed1998

Gap junctional communication and the tyrosine phosphorylation of connexin 43 in interaction between breast cancer and endothelial cells.

Abnormal gap junction communication (GJC) has been associated with carcinogenesis. We investigated the role of endothelial cell GJC and connexin 43 (Cx43), the main gap junction protein in these cells, during tumour cell extravasation. GJC was determined by the ability of cells to transfer Lucifer yellow, to neighbouring cells. Tumour-endothelial interaction was assessed by DiI assay. Connexin 43 expression and tyrosine phosphorylation were measured by immunoprecipitation and Western blotting. Co-culturing of ECV304 endothelial cells with human breast cancer cells resulted in a rapid and transient loss of communication competence of ECV304. This inhibition was maximal within 5 min. GJC was almost fully restored in 2 h. The co-culturing also resulted in an increase in the tyrosine phosphorylation of CX43. The pattern of phosphorylation was similar to the loss and the recovery of GJC in ECV304. We conclude that interaction of tumour cells with endothelium effectively inhibits GJC of endothelial cells, which is attributed to the increased tyrosine phosphorylation of connexin 43. This may contribute to the extravasation of tumour cells from the circulation, an essential step in the establishment of metastasis.

Adenocarcinoma↗
PubMed1997

The clinical behavior of breast carcinoma is probably determined at the preinvasive stage (ductal carcinoma in situ).

BACKGROUND: Mammography has greatly increased the number of women diagnosed with ductal carcinoma in situ (DCIS) of the breast. New classifications of DCIS recently have been proposed. In this study, these classifications were applied to DCIS associated with invasive tumors and correlated with patient prognosis. METHODS: Three hundred cases of infiltrating ductal carcinoma of the breast in which there was associated DCIS in the surrounding breast were studied. The DCIS was classified as well, moderately, or poorly differentiated, according to two recently published systems using the cytonuclear features of the malignant cells (Holland classification) and cytology and the presence of necrosis (Van Nuys classification). RESULTS: The differentiation of DCIS was significantly correlated with the grade of the invasive carcinoma (P < 0.0001), the Nottingham prognostic index (P < 0.0001), and the clinical outcomes of the patients (P < 0.0001). CONCLUSIONS: These findings indicate that a model in which there is increasing in situ dysplasia before the development of stromal invasion is incorrect for breast carcinoma. Rather, in most cases, well-differentiated DCIS probably gives rise to low grade invasive breast carcinoma with a better long term clinical outcome. These data suggest that many of the important prognostic biologic and genetic characteristics of breast carcinoma are already established in the neoplastic clones of malignant cells at the preinvasive stage of the disease.

Breast Neoplasms↗
PubMed1997

Gamma linolenic acid regulates expression of maspin and the motility of cancer cells.

Maspin, mammary serine protease inhibitor, is a recently identified tumour suppressor and has a profound effect on cell motility. This study examined the effect of gamma linolenic acid (GLA), an essential fatty acid (EFA) with anticancer properties, on the expression of maspin and motility of cancer cells. Six human cell lines including colon cancer, mammary cancer, and melanoma were used. Expression of maspin protein was determined by immunocytochemistry & Western blotting. Maspin mRNA was detected with reverse transcription-PCR (RT-PCR). Four of the six cell types expressed maspin with MDA MB 231 and ECV304 (endothelial cell) being negative. Treatment of these maspin positive cells with gamma linolenic acid (GLA) resulted in a concentration dependent stimulation of the expression of maspin protein with the effects seen as early as 4 hours. Linoleic acid had an inhibitory effects. Alpha linolenic acid and arachidonic acid had no significant effect. The mRNA levels from cells treated with GLA was seen to increase as shown by RT-PCR. Cell motility, monitored with time-lapse video recording and Hoffmann microscopy, showed a marked reduction in terms of spreading and migration on extracellular matrix coated surface. This reduction was reversed with anti-maspin antibody. It is concluded that GLA, a member of then-6 series of EFAs, up-regulates the expression of maspin which is associated with a reduction in the motility of cancer cells.

Breast Neoplasms↗
PubMed1997

E-cadherin (E-cad) expression in duct carcinoma in situ (DCIS) of the breast.

E-cadherin (E-cad) is an epithelial cell-cell adhesion molecule whose loss or reduced expression is associated with a more invasive tumour phenotype. Ninety-six cases of screen detected pure ductal carcinoma in situ (DCIS) were analysed immunocytochemically for expression of E-cad using the HECD-1 mouse monoclonal antibody. The in situ component in each case was classified on the basis of cytonuclear grade, extent of necrosis, Van Nuys classification and a newly devised Cardiff classification. The amount of E-cad expression was assessed semi-quantitatively using an intensity distribution method. There is significantly more expression of E-cad in well-differentiated DCIS when compared with poorly differentiated DCIS and this finding is highly significant (P < 0.001) irrespective of the classification system used. These findings suggest that progressive loss of E-cad expression may occur at an early stage of breast cancer development.

Breast Neoplasms↗
PubMed1997

A randomized controlled trial of prophylactic isolated cytotoxic perfusion for poor-prognosis primary melanoma of the lower limb.

A randomized controlled trial of prophylactic isolated hyperthermic limb perfusion (IHLP) using melphalan at 2 mg/kg body weight has been performed on a total of 30 patients with primary melanoma of the lower limb > or = 1.7 mm thick. Excision (control, n = 14) was compared to excision plus IHLP (n = 16). The two groups were well matched for sex, tumour thickness and duration of follow-up (control group median: 63 months (range: 16-108), perfusion group median: 80 months (range: 37-113)). Recurrent disease developed in nine of the control group, seven of whom have died. In the perfusion group only two patients have developed recurrent disease, both of whom have died (recurrence: P < 0.004, mortality: P < 0.03, using Fishers' exact probability test). Inguino-femoral nodal recurrence occurred in five of nine control patients, but in only one patient in the perfusion group. These data support the use of adjuvant IHLP in the management of poor-prognosis primary melanoma of the lower limb.

Actuarial Analysis↗
PubMed1997

Evaluation of general practitioner referrals to a specialist breast clinic according to the UK national guidelines.

The recently published national guidelines to general practitioners for the referral of patients with breast problems were retrospectively applied to letters of all patients attending the Rapid Access Breast Clinic at the University Hospital of Wales. The patients have all had diagnostic investigations performed at the initial visit with a multidisciplinary review of results and provision of a management plan prior to the subsequent visit. Since its inception in May 1995 until the end of the year when the guidelines were published, 2332 new patients had been seen. Overall, 29% of patients with benign breast disease would not have been referred if the guidelines had been strictly followed. Of the 147 symptomatic carcinomas diagnosed from general practitioner referrals (6.3% of total referrals), no invasive cancers would have been missed. One patient with incidental detection of ductal carcinoma in situ (DCIS) in the asymptomatic contralateral breast would not have been referred. Referral for pain without a discrete lump constituted 63% of the patients with a benign diagnosis who fell outside the guidelines. The guidelines also include comprehensive algorithms for the initial management of benign breast symptoms that do not require immediate referral by the general practitioners. Our general practitioners were significantly better at referring patients over 50 years old but the proportion of appropriate referrals were not related to the number referred by each practice. The present guidelines adequately cover referral for the diagnosis of malignant breast disease to a specialist, and may reduce the benign workload of breast clinics.

Ambulatory Care Facilities↗
PubMed1997

Gamma linolenic acid regulates gap junction communication in endothelial cells and their interaction with tumour cells.

Tumour-endothelial cell adhesion forms a key role in the establishment of distant metastases. This study examined the effect of gamma linolenic acid (GLA), an anti-cancer polyunsaturated fatty acid (PUFA), on both the gap junction communication of human vascular endothelial cells and tumour cell-endothelial interactions. By using scrape loading of Lucifer yellow dye, we showed that GLA at non-toxic levels increased Lucifer yellow transfer, indicating improved gap junction communication. The fatty acid also corrected the communication that was reduced by the mitogenic and motogenic factor HGF/SF. GLA inhibited the tyrosine phosphorylation of connexin-43, a protein that formed gap junction in this cell. When human tumour cells were added to quiescent or HGF/SF-activated endothelial cells, the presence of GLA reduced adhesion of tumour cells to the endothelium. It is concluded that GLA reduces tumour-endothelium adhesion, partly by improved gap junction communications of the endothelium.

Breast Neoplasms↗
PubMed1997

Regulation of desmosomal cell adhesion in human tumour cells by polyunsaturated fatty acids.

Desmosomes are key structures in cell-cell adhesion. In this study we examined the effect of n-6 essential fatty acids on the expression of desmoglein (Dsg), desmosomal cadherin and the formation of desmosomes in E-cadherin negative human breast, colon and lung cancer cells and melanoma cells. Electron microscopy revealed that cells cultured with gamma linolenic acid (GLA) showed increased cell-cell adhesion together with an increase in the formation of desmoglein-containing desmosomes. Western blotting studies of cellular proteins demonstrated that, following culture with fatty acids, Dsg expression was modified, with the greatest increase seen after GLA treatment. Other fatty acids increased Dsg expression, but to a lesser extent. It is concluded that GLA regulates desmosome-mediated cell-cell adhesion in human cancer cells, particularly in cells without E-cadherin.

Cadherins↗
PubMed1997

Visiting registrars in surgery: the trainees' viewpoint.

Overseas Doctors have been coming for higher surgical training to the UK for many years. Little is known about the reasons they choose to come here, what their expectations are and if the training they receive fulfils these expectations and prepares them for a career back home. The aim of this study was to address these questions and to see what changes could be suggested to make training more meaningful to visiting registrars. Questionnaires were sent to 26 trainees who were part of the 3 year surgical registrar rotation in Wales from 1992. 23 completed questionnaires were available for analysis as the others were not traceable. 83% came to the UK to obtain the FRCS and train in a specific aspect of general surgery (74%). The period of training was felt to be inadequate by 79% of trainees. 65% felt that of the total period of training, less than 75% was useful. On return to their own countries 96% were to be either solely or largely responsible for patients in their care. In conclusion, if surgical training is to remain meaningful to visiting trainees, changes would have to be made to the Calman system to enable them to continue to do the FRCS and avenues made available for them to train in their stated areas of interest with adequate supervision, regular assessment and certification.

Attitude of Health Personnel↗
PubMed1996

Cyclosporin A and multiple fibroadenomas of the breast.

Multiple bilateral fibroadenomas are uncommon. This finding in four women who had received renal transplants prompted further inquiry. A prospective study was performed on 39 women under the age of 55 years who had received a renal transplant at least 1 year earlier. Clinical examination and breast ultrasonography were performed. Factors considered included immunosuppressive therapy, concurrent medication and renal function. Blood was taken for estimation of oestradiol, prolactin, follicle-stimulating hormone (FSH) and sex hormone binding globulin levels. Fibroadenomas were found in 13 of 29 women who had received cyclosporin A: multiple in ten and bilateral in five. No abnormal breast findings were seen in 10 patients immunosuppressed with steroids and azathioprine alone (chi 2 = 7.30, 1 d.f., P < 0.01). Serum oestradiol concentration was raised in women with fibroadenomas compared with that in those with normal breasts (P < 0.05) and the level of FSH was lower (P < 0.01). Cyclosporin A may act on breast fibroblasts by humoral mechanisms and direct action.

Adult↗