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Biomedical subjects

R E Mansel

Publications and source records attributed to R E Mansel.

At least 145 records · Page 8Linked to original sources

A new microbioassay for the measurement of lactogenic hormones in human serum.

The standard Nb2 assay for biologically active prolactin has been modified to allow a rapid convenient microbioassay without loss of specificity or accuracy. Lactogenic hormones specifically stimulate the replication of Nb2 node rat lymphoma cells in suspension culture and form the basis of a currently available bioassay to measure prolactin and growth hormone in human serum. A new microbioassay was developed using microtest plates enabling a large number of samples to be assayed simultaneously whilst maintaining the overall sensitivity of the bioassay for lactogenic hormones. Growth of the Nb2 node lymphoma cells, measured by a light scattering technique using optical density on a spectrophotometer, was shown to be closely correlated with the cell number determined on a Coulter counter. Addition of excess anti-human prolactin and anti-human growth hormone completely inhibited the growth stimulatory effects of both human prolactin and human growth hormone. This new microbioassay (BA) and conventional radioimmunoassay (RIA) were used to measure lactogenic hormones in 48 normal subjects. There was a close correlation between the results of both assays for each hormone studied in the control sera. The mean basal BA/RIA ratio was 1.5 (range 0.8-2.0) for prolactin, 0.7 (range 0-4.5) for growth hormone and 1.3 (range 0.5-1.9) for total lactogenic activity.

Adult↗

Low-dose danazol for mastalgia.

A low-dose danazol maintenance therapy (mean total dose 800 mg per month) was given during the luteal phase to 34 women with severe relapsing cyclical mastalgia. On conventional danazol dosage, all subjects had previously obtained a useful clinical response, but side effects occurred in 29 (85 per cent). Using this low-dose regimen, complete relief of symptoms was achieved in 15 women (44 per cent); the remainder obtained a substantial clinical improvement. Side effects were reduced to 12 per cent of women and were considered mild and tolerated by all patients. A low-dose regimen may be suitable for women with severe persistent cyclical mastalgia and minimises side effects that develop on conventional dosage.

Adult↗

Maintenance therapy of cyclical mastalgia using low-dose danazol.

In an open study, low-dose danazol (mean total dose 700 mg/month) was given during the luteal phase to 20 women with severe relapsing cyclical mastalgia. All subjects had previously obtained a useful clinical response on conventional dosage of danazol, but side effects occurred in 13 (65%). On the low-dose regimen, complete relief of symptoms was attained by 11 women (55%) and the remainder achieved a substantial clinical improvement; no side effects were reported. A low-dose regimen may be suitable for women with chronic relapsing cyclical mastalgia or those who develop side effects on conventional dosage.

Adult↗

Role of Doppler ultrasound flowmetry in the diagnosis of breast lumps.

One hundred and five patients with discrete breast lumps were examined with a 10 MHz Doppler ultrasonic flowmeter. Doppler flow signals were analysed on an Angioscan spectrum analyser. Recordings from the opposite normal breast were taken as controls and signals from the two sides compared. In 23 patients signals from the normal breast could not be recorded and therefore results of the remaining 82 patients are reported. These included 39 patients with carcinoma, 20 with fibroadenoma, 12 with cyclical nodularity and 11 with cysts. Malignant lumps exhibited significantly higher peak systolic (S) and minimum diastolic frequencies (D) in comparison to the control breast. Fibroadenoma also had a higher S and D than those of the opposite normal breast. Signals over cysts and cyclical nodularity showed no significant difference from the recordings over the control side. Despite significantly higher systolic and diastolic frequencies in the cancer group in comparison to benign lumps and normal breast, considerable overlap in the values was seen between cancer and other groups. Therefore the patterns on 10 MHz Doppler sonography are not sufficiently specific to discriminate benign from malignant breast lumps.

Adenofibroma↗

Aberrations of normal development and involution (ANDI): a new perspective on pathogenesis and nomenclature of benign breast disorders.

A framework for understanding and management of benign breast disorders is presented, based on the notion that most breast complaints can be explained as minor aberrations of the normal processes of development, cyclical change, and involution. The generic term ANDI (aberrations of normal development and involution) is introduced to allow breast problems to be placed within an overall framework of pathogenesis; this concept also permits more detailed individual assessment with respect to normality and disease. Fibrocystic disease and its synonyms are discarded in favour of terms that are strictly descriptive of the clinical and/or histological picture.

Adenofibroma↗

Mitogenicity of human fibroblasts in vivo for human breast cancer cells.

Stromal factors have been implicated in the regulation of mammary epithelial cell behaviour, but their influence on human breast cancer is unknown. Fibroblasts were grown in monolayer cell culture from explants of benign and malignant breast tissue and normal skin. MCF7 human breast cancer cells alone (2 X 10(6) cells) or in combination with live fibroblasts (MCF7 + F) were inoculated into the mammary fat pads of 6-8-week-old female nude mice. After 5 weeks tumours were excised, weighed and fixed for histological examination. Addition of live breast fibroblasts significantly increased the retrieval (127/135 versus 52/106, P less than 0.01, chi 2 test) and growth (tumour weight 174 +/- 11 versus 41 +/- 4 mg, mean +/- s.e.m., P less than 0.01, Mann-Whitney U test) of subsequent tumours. Histological examination did not reveal any morphological difference between the two tumour groups. Injection of fibroblasts alone did not produce tumours. Addition of skin fibroblasts was also stimulatory. Glutaraldehyde-killed fibroblasts increased tumour take but did not stimulate tumour growth. Mononuclear blood leucocytes were ineffective. The results demonstrate that, in this model, fibroblasts exert stimulatory influences on human breast cancer xenograft growth and development.

Adenocarcinoma↗

Presence and possible significance of immunohistochemically demonstrable prolactin in breast apocrine metaplasia.

Paraffin wax embedded formalin-fixed benign breast disease tissue taken from 17 patients (15 with microcystic disease and 2 with fibroadenoma) was studied for the presence of tissue bound prolactin using a rabbit antiserum against human prolactin applied in conjunction with a highly sensitive modified version of the dinitrophenyl (DNP)-hapten sandwich staining (DHSS) procedure. Sections taken from 14 of the 15 cases showing apocrine cystic changes exhibited strong prolactin staining restricted to the cytoplasm of metaplastic apocrine cells lining the cysts. Normal lobules and ducts and blunt duct proliferations were all negative, as were also the two cases of fibroadenoma. In contrast 6 out of 8 cases of breast cancer examined showed heterogenously distributed cytoplasmic staining in the cancer cells. Maximal prolactin staining in the apocrine cells was observed at antiserum dilutions as high as 1:60,000. This compared favourably with a 1:120,000 dilution that gave maximal levels of staining in the prolactotrophs present in serial sections taken from formalin fixed paraffin wax embedded post mortem human anterior pituitaries. In both types of tissues the specific staining was abolished by pre-absorption of the antiserum with human prolactin (10 micrograms ml-1). No staining was observed when the anti-prolactin serum was either omitted or substituted with DNP-labelled normal rabbit serum. Apocrine metaplasia in cystic disease of the breast has recently been found to be associated with an increased breast cancer risk. The strong and selective presence of immunohistochemically demonstrable prolactin in the metaplastic cells may be of significance in view of the hormone's known growth stimulating effect on the breast epithelium.

Adenofibroma↗

Inhibition of protein kinase C mediated signal transduction by tamoxifen. Importance for antitumour activity.

Recent studies have demonstrated tamoxifen inhibition of the enzyme protein kinase C (PKC) in vitro. The aim of this study was to investigate the effects of tamoxifen on PKC function in intact human cells. As PKC activates the neutrophil oxidase mechanism the neutrophil was chosen as an experimental model to assess PKC-tamoxifen interaction in these experiments. Neutrophils from healthy volunteers were separated by centrifugation through Ficoll Hypaque. Two separate parameters of oxidase activation; oxygen consumption and reactive oxygen metabolite production were monitored by a Clark electrode chamber and luminol dependent chemiluminescence respectively. Neutrophil chemiluminescence was markedly stimulated by 4 Phorbol-12 myristate-13 acetate (PMA). This stimulation was inhibited by tamoxifen; IC50 = 6.1 +/- 1.6 microM (means +/- S.E.M.) N = 6. Neutrophil oxygen consumption was similarly stimulated by PMA and inhibited by tamoxifen. The tamoxifen inhibition was not due to cell toxicity as assessment of cell integrity by the exclusion of trypan blue and measurement of intracellular concentrations of ATP showed no significant differences before and after treatment. Tamoxifen also inhibited neutrophil chemiluminescence which was stimulated by oleoyl acetyl glycerol and mezerein excluding interaction with PMA as an explanation of its inhibitory effect. These results are consistent with tamoxifen inhibition of PKC function in intact human cells. This may be central to its antitumour action.

Diglycerides↗

Daily salivary progesterone levels in cyclical mastalgia patients and their controls.

Progesterone levels were measured in samples of saliva collected daily throughout the menstrual cycle in patients with pronounced cyclical mastalgia and breast nodularity. A control group matched for age, length of menstrual cycle and parity was also studied. No significant differences in progesterone levels were detected between the two groups for the luteal phase of the cycle. These data indicate that cyclical mastalgia is not associated with significant luteal phase progesterone insufficiency, as demonstrated by salivary levels and, by implication, serum levels of progesterone.

Adult↗

Cosmetic results of immediate breast reconstruction post-mastectomy: a follow-up study.

We reviewed 95 patients who underwent immediate breast reconstruction at the time of mastectomy at least one year after operation for assessment of cosmetic results and complications. There were 45 rectus abdominis and 38 latissimus dorsi myocutaneous flaps used for reconstruction. Twelve patients had subpectoral implants without a flap. The results show a remarkable concordance of assessment by patient and surgeon: both found simple subpectoral prosthesis insertion to be inferior to flap reconstruction. Flap reconstruction gave satisfactory results in the majority of patients; latissimus dorsi and rectus abdominis flaps gave similar cosmetic results. However rectus abdominis flaps showed a higher complication rate of flap necrosis and incisional hernia of the abdominal wound. Psychological assessment showed no differences between the three types of reconstruction. We conclude that immediate breast reconstruction can give excellent cosmetic results, and provides an acceptable and safe means of ameliorating the effects of mastectomy. The number of grossly unsatisfactory results decreased notably as the series progressed. Experience and meticulous attention to detail are necessary, since many patients are unwilling to have revisionary procedures if the initial result is unsatisfactory.

Breast↗

Segmental abdominal herpes zoster paresis.

A case of segmental abdominal paresis due to thoraco-abdominal herpes zoster in a 63 year old man is reported. This is caused by peripheral motor paresis. It has a good prognosis with spontaneous resolution.

Abdomen↗