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Biomedical subjects

R E Mansel

Publications and source records attributed to R E Mansel.

At least 163 records · Page 9Linked to original sources

Monoclonal antibody identification and characterization of a Mr 43,000 membrane glycoprotein associated with human breast cancer.

A monoclonal antibody (323/A3) with a high degree of selectivity for binding to breast cancer cells was produced by immunization of mice with MCF-7 human breast cancer cells. The antigen recognized by 323/A3 on MCF-7 appears to be surface localized, and by enzyme-linked immunosorbent assay, the antibody was found to bind strongly with four of six breast cancer cell lines examined while no binding was detectable with nonbreast cancer cell lines. In vivo distribution of the 323/A3 antigen was screened by immunoperoxidase staining of formalin-fixed paraffin sections of normal human tissues and tumors. Among breast tissues, positive staining was detected with 75% (6 of 8) of metastatic lymph nodes, 59% (76 of 128) of primary breast tumors, 20% (13 of 63) of benign breast lesions, and 0% (0 of 10) of normal breast. No immunostaining was detected with a large variety and number of other normal human tissues with the exception of staining observed with epithelium of normal colon. Antigen distribution appears not to be disease specific, since positive staining was also observed with adenocarcinomas other than breast. The antigen recognized by the 323/A3 antibody was identified by Western blot analysis as a Mr 43,000 protein. The glycoprotein nature of the antigen was demonstrated by its binding to concanavalin A, specific elution with sugar, and immunoprecipitation of a Mr 43,000 radiolabeled protein from extracts of MCF-7 cells after pulse labeling with [3H]glucosamine. The 323/A3 antigen appears to be the same Mr 43,000 protein in cell lines as in breast tumors in vivo. Based on a comparison with the molecular weights of other known tumor-associated antigens and with their immunocytochemical tissue distribution, the Mr 43,000 glycoprotein described here represents a tumor-associated antigen previously undescribed in breast cancer or in other tumors. Since the Mr 43,000 glycoprotein is present on the surface of most breast cancer cells and is either absent or expressed at very low levels in most normal tissues including normal breast, the monoclonal antibody described here may have potential applications in diagnosis and management of breast cancer.

Antibodies, Monoclonal↗

Clinical experience of drug treatments for mastalgia.

Results of randomised trials and open studies in 291 patients with severe persistent breast pain in whom breast cancer had been excluded showed that drug therapy produced a good or useful result in 77% of those with cyclical mastalgia and 44% of those with non-cyclical mastalgia. In patients with cyclical mastalgia good or useful responses were obtained with danazol in 70%, with bromocriptine in 47%, and with evening-primrose oil in 45%. The equivalent response rates in patients with non-cyclical mastalgia were 31%, 20%, and 27% respectively. Progestagens were not effective in either group. Failure to respond to one drug did not preclude response to a different drug. Patients with Tietze's syndrome did not respond to drug therapy, but 7 out of 10 responded to injection of lignocaine and hydrocortisone around the affected costochondral junction.

Breast↗

Prediction of response to endocrine therapy in pronounced cyclical mastalgia using dynamic tests of prolactin release.

Many of the endocrine agents currently used to treat symptomatic benign breast disease modify the action or secretion of prolactin. We have compared the responses to hormonal therapy with dynamic assessment of prolactin control in 29 patients with cyclical mastalgia and in 7 patients with non-cyclical mastalgia. The tests of prolactin release used were direct stimulation by TRH or dopaminergic blockade by domperidone. These were carried out before treatment in the mastalgic patients and also in 22 age-matched asymptomatic controls. The response to treatment was assessed using a special pain chart and visual linear analogue scale. Patients with cyclical mastalgia could be divided into two groups: those in whom the peak prolactin release was exaggerated (greater than 4000 mU/l) and those in whom the prolactin release was less marked and similar to control subjects and patients with non-cyclical mastalgia. Patients in the cyclical mastalgia group with a high peak prolactin release responded to hormonal treatment significantly more frequently (90%) than those with a normal prolactin release (50%). Basal prolactin levels did not correlate with the response to treatment. In the non-cyclical mastalgia group, no patient had peak prolactin release greater than 4000 mU/l and none responded to therapy. This study indicates that dynamic tests of prolactin release in cyclical mastalgia may be useful in predicting the subsequent satisfactory response to endocrine therapy if a high peak prolactin release is induced.

Adult↗

Prolactin response to thyrotropin-releasing hormone stimulation and dopaminergic inhibition in benign breast disease.

Pituitary function was tested in predefined clinical groups of benign breast disease under strictly controlled clinical and laboratory conditions. Two different tests of prolactin storage and control mechanisms, direct stimulation by thyrotropin-releasing hormone (TRH) and inhibition of dopaminergic control by domperidone, indicate a significant abnormality in patients with severe cyclical mastalgia and nodular breast disease (P less than 0.05 and P less than 0.002), but not in those with noncyclical mastalgia. No abnormalities of thyroid function were found.

Adult↗

Immediate reconstruction of the breast after mastectomy. Is it safe?

The authors have reviewed the results of their first 85 immediate reconstructive procedures following mastectomy for breast cancer. acceptable cosmetic results were obtained in most patients with no mortality or life-threatening morbidity. There were a number of problems related to the wounds and the prostheses, which decreased with increasing experience. There was a moderate increase in blood transfusion requirements, and a considerable increase in operating time. No detrimental effect on tumor behavior was observed when assessed as part of a case-control study. It is concluded that this approach is feasible and safe, and deserves further evaluation.

Adult↗

Altered responses of prolactin, luteinizing hormone and follicle stimulating hormone secretion to thyrotrophin releasing hormone/gonadotrophin releasing hormone stimulation in cyclical mastalgia.

A generalized abnormality of hypothalamopituitary function was found in 17 patients with cyclical pronounced mastalgia compared with 11 controls by using a combined thyrotrophin releasing hormone and gonadotrophin releasing hormone test. The release of prolactin, luteinizing hormone and follicle stimulating hormone was significantly greater in cyclical mastalgia patients than in controls. Basal thyrotrophin, T3 and T4 levels were within the normal range in both groups indicating normal thyroid status in benign breast disease. The single measurement of oestrogen and progesterone in the luteal phase was not abnormal. These data demonstrate an alteration in lactotroph and gonadotroph function in patients with cyclical mastalgia. It is unknown at present whether this represents an appropriate cellular response to altered central or peripheral signals. There is no evidence to suggest, however, that the anterior pituitary cell types are abnormal per se.

Adult↗

Circadian breast skin temperature rhythms: overt and occult benign and occult primary malignant breast disease.

Circadian variations of breast surface temperature have been measured in patients with overt or occult benign breast disease, or in those with occult breast cancer. Subjects were studied in a hospital ward environment well-controlled with respect to ambient temperature. Using manual techniques temperatures were recorded half-hourly for 96 hr from replicate sensors placed on quadrants of the left and right breasts inclusive of tumour areas and similar sites on the contralateral breast. Application of time series analysis failed to consistently demonstrate differences in values for the rhythm parameters for the tumour area and contralateral site. It was apparent, however, that the tumour area was generally associated with a reduced initial variance of the series in addition to a reduced percentage variance explained by a time series model with two rhythmic components when compared to the control site. These data suggest that efforts to identify early breast disease from signals of breast temperature should, at least, be directed to studies of temperature variance.

Adult↗

Natural history of breast pain.

258 patients with breast pain were restudied 2 to 7 years after initial assessment in a special mastalgia clinic. Pain persisted at follow-up in 65% of patients. Mastalgia was cyclical in two-thirds. Mean duration of pain in patients experiencing complete relief before follow-up examination was 6.8 years, while duration of pain persisting at follow-up ranged from 2 to 30 years. In patients who had relief or substantial improvement in pain, the improvement was spontaneous in 22% and resulted from a hormonally related event--menopause, pregnancy, or use of oral contraceptives--in the remainder. Onset of cyclical pain before the age of 20 years was followed by a prolonged course. A quarter of the patients had non-cyclical pain. There were two populations of patients in this group. One experienced relief after a mean of 3 years, and in the other pain still persisted after 2-22 years. Relief was spontaneous in one half, and rarely followed a hormonally related event. About 70% of the patients, with both cyclical and non-cyclical pain, considered that their pain had warranted active treatment. This study indicates that the type of pain and age at onset may allow some prediction of the course of the disease and may aid the choice of therapy.

Adult↗

Importance of mastalgia in operable breast cancer.

The importance of pain as a presenting symptom of breast cancer has been assessed in a series of 240 patients with operable breast cancer over four years. From an analysis of the case histories of 36 patients the diagnosis proved difficult in one-quarter of the cancers. This is explained by the high incidence of subclinical and lobular carcinoma in the group. Cancer must be seriously considered as a diagnosis in patients presenting with well-localised breast pain of recent onset. These patients should be followed for at least one year after the onset of the pain before cancer is confidently excluded.

Adult↗

Controlled trial of the antigonadotropin danazol in painful nodular benign breast disease.

In a double-blind crossover study of the effects of the antigonadotropin danazol on pain and nodularity in 28 women with cyclical mastalgia danazol was given at doses of 200 mg/day and 400 mg/day, and the responses were assessed both subjectively and objectively. Danazol caused a significant and progressive decrease in breast pain and nodularity when compared with placebo. Symptoms responded more quickly with the 400 mg/day dose of danazol than with the 200 mg dose, but the larger dose also caused greater side-effects. Danazol is a useful addition to the range of antihormones that can be used to suppress the symptoms of severe hormone-related benign breast disease.

Adult↗

Duct ectasia in the male.

Three cases of inflammatory duct ectasia occurring in the male breast are described. The clinical presentation of the disease in the male closely resembles that in the female. Nipple retraction, nipple discharge, periareolar inflammation and bilateral involvement are all seen. Conservation measures produced unsatisfactory results similar to those in women. A similar operative approach to that used in women is advocated.

Breast↗

The interpretation of mammographic ductal enlargement in cancerous breasts.

The xeromammograms of 128 women with breast cancer were coded radiologically according to Wolfe's gradings. The mastectomy specimens were then histologically examined for the presence of ductal abnormality. The ducts were found to be normal in the cases coded as normal radiologically but they were not always abnormal histologically when considered to be abnormal radiologically. 'Ductal prominence' may be due to duct ectasia, intraduct hyperplasia or periductal collagenosis.

Breast↗

Mastalgia: psychoneurosis or organic disease?

To test the traditional surgical view that pain in the breast is largely an expression of psychoneurosis, the Middelesex Hospital Questionnaire was given to 317 women with mastalgia and 170 controls with varicose veins. Their scores were compared with those of 173 women psychiatric outpatients tested by the designers of the questionnaire. The results were broadly similar in the mastalgia and varicose veins groups, and where there were significant differences women with varicose veins had a higher psychoneurotic score in each case. Within the mastalgia group no difference in scores was observed between patients with cyclical mastalgia and those with mastalgia due to periductal mastitis. Both groups of surgical outpatients had significantly lower scores in major traits than the psychiatric group, except for a small group of patients with breast pain who persistently failed to respond to treatment. Patients with mastalgia are therefore no more "neurotic" than those with varicose veins, and differ greatly from patients with recognized psychoneurosis. Most patients have a physiological or pathological basis for their breast pain, and they deserve an appropriate diagnostic and therapeutic approach.

Adult↗

A double blind trial of the prolactin inhibitor bromocriptine in painful benign breast disease.

A double blind crossover trial of the prolactin inhibitor bromocriptine in painful benign breast disease is reported. Twenty-nine women with cyclical mastalgia and 11 with non-cyclical pain were treated with bromocriptine, 5 mg daily, and placebo over six menstrual cycels. Assessment of response to treatment was made by a linear analogue system and clinical examination together with plasma prolactin estimations. Bromocriptine produced a significant improvement in breast symptoms and a significant fall in prolactin levels in the cyclical pain group, but had no effect in the non-cyclical group. These results suggest that bromocriptine offers a new and effective approach in the management of cyclical breast pain.

Breast Diseases↗

The surface ultrastructure of ganglia.

The surface ultrastructure of ganglia has been studied using the scanning electron microscope. This study showed that the ganglion wall consists of multidirectional strata of collagen fibres and has no cellular lining. The wall has a sponge-like appearance and does not appear degenerate or necrotic. Comparison with synovial membrane and adventitious bursa confirmed that these are distinct structures which have a cellular lining. Ganglia probably arise from the multifunctional mesenchymal cells which are found within their walls. The ganglion fluid may also originate from these cells.

Collagen↗