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Biomedical subjects

H W Simpson

Publications and source records attributed to H W Simpson.

At least 37 records · Page 2Linked to original sources

Immunocytochemical demonstration and significance of p21 ras family oncogene product in benign and malignant breast disease.

It has been suggested that the immunocytochemical demonstration of the p21 ras oncogene product is a useful marker of malignancy in breast disease. We have studied the reactivity of a series of specimens of benign and malignant breast disease with the anti ras p21 monoclonal antibody Y13-259, and shown widespread positive staining in both benign and malignant (including metastatic) disease as well as in adjacent 'normal' epithelium. In addition some staining of stromal cells as well as nerve fibres was observed. Our results suggest that the presence of ras p21 protein as demonstrated by this antibody is not a useful marker of malignancy or of proliferating epithelium but is rather a normal feature of certain cell types.

Adenofibroma↗

A critical investigation of the Oxford tumour marker Ca1 in the histological diagnosis of breast cancer and pre-cancer.

Ca1 antibody reacted focally with all of the 20 cancers examined, but also with 12 out of 13 fibroadenomata and with each of 20 normal breasts. These observations indicate that there are severe limitations to the use of Ca1 antibody for defining benign versus malignant processes. Ca1 is most specific in terms of the cytoplasmic staining of tumours versus normal tissues. If a hierarchy of maximal staining is drawn up, cancers and fibroadenomata appear at the top, with normal tissue found in various types of breast in the middle, and non-neoplastic lesion such as epitheliosis, hyperplasia and apocrine change at the bottom of the hierarchy. There is a growing list of non-cancerous tissues which show reactivity to Ca1. In July 1983 this list numbered about 15. The designation 'Ca' is inappropriate.

Adolescent↗

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↗

Bimodal age-frequency distribution of epitheliosis in cancer mastectomies: relevance to preneoplasia.

A census of epitheliosis in 500 consecutive cancer mastectomies has been carried out. The probability of concurrence of this phenomenon with cancer has a bimodal age-frequency distribution. It is high in cancer mastectomies from women in their early 40s, low in the late 50s and high again in the elderly. Epitheliosis during the reproductive life span is regarded as a reversible ovary-dependent abnormality. It is greatly increased in the premenopausal cancerous breast and it is thought that it carries increased risk for cancer initiation. In contrast the probability of epitheliosis in the breast in the elderly cancer patient is only slightly greater than in "noncancerous" post mortem breasts of similar age. Much of this "epitheliosis" may represent, in fact, indolent autonomous cancer though a small proportion could be epitheliosis supported by extraovarian estrogen.

Adult↗

Characterisation of breast skin temperature rhythms of women in relation to menstrual status.

Circadian breast skin temperature rhythms were characterised throughout the menstrual cycle, for various locations on the left breast of ambulatory women. All subjects exhibited highly significant circadian rhythms (P less than 0.001). Changes in rhythm parameters, such as the mesor, amplitude and acrophase, were observed during the menstrual cycle. No consistent trend in these rhythm parameters was observed between subjects in relation to menstrual cycle stage. Experimental and statistical techniques used to characterise circadian rhythms in pre-menopausal women were applied to a post-menopausal woman with primary breast cancer. Comparison of rhythm parameters associated with the tumour area and corresponding site on the contralateral breast showed abnormal thermal characteristics such as elevated mesor values, decreased amplitude as well as changes in the timing of the acrophase. These properties may be exploited for the early detection of breast cancer. The project also involved the design and testing of an ambulatory device, known as the 'chronobra', for the measurement of breast skin temperature. The performance of the chronobra was in close agreement with reliable, conventional equipment. The chronobra now allows studies of breast skin temperature rhythms associated with breast disease to be extended.

Adolescent↗

Hydrochlorothiazide diuresis in healthy man: review of the circadian mediation.

This is a review of evidence for a circadian-mediated pharmacology of a single dose of hydrochlorothiazide in normal man. The normal circadian rhythms of urine volume and electrolytes are discussed in detail. Information is documented that hydrochlorothiazide diuresis, in normal subjects on a normal schedule of diurnal activity/nocturnal rest, progressively increases for 4 h after a.m. administration and for 8 h after p.m. administration. This suggests that the therapeutic efficiency of a single dose may be enhanced (nearly 50%) by the simple expedient of prescribing in the afternoon. No information is provided as to whether the circadian-mediated response appertains in disease or with continued drug administration. The word 'circadian' is not found in classical pharmacological texts although many examples of circadian-mediated drug action have now been described. A circadian reappraisal of drug effects in general is overdue.

Chlorides↗

A circadian variation of melphalan (L-phenylalanine nitrogen mustard) toxicity to murine bone marrow: relevance to cancer treatment protocols.

The toxicity of Melphalan to murine bone marrow was assessed by automated Coulter counts of femoral marrow nucleated cells. A significant dose-response slope (p less than 0.001) was shown and also a significant variation along the 24 h scale. With food available ad libitum and light from 06.00 to 18.00 hours, the minimum marrow depression occurred around 16.00 hours. Extrapolating these findings to human chemotherapy it would appear that prescription of the drug during the early part of the activity span (usually breakfast) will minimize marrow depression. This differs from a human study in which Melphalan was given at 'bedtime' as an adjuvant to mastectomy in breast carcinoma and in which there was leucopenia at some stage of treatment in all 103 patients. It is recommended that in future cancer therapy protocols test for circadian variability of white cell depression by varying treatment times systematically along the 24 h scale.

Animals↗

Circadian rhythmicity of human plasma cortisol and PHA-induced lymphocyte transformation.

In two experiments, lymphocytes from six healthy subjects were sampled every 4 hr, counted, and cultured with PHA. Plasma cortisol in the same blood samples was measured and showed an expected circadian variation in level. A circadian rhythm in lymphocyte transformability to PHA was found to coincide directly with the cortisol level but varied inversely with lymphocyte numbers. The relationship between cortisol and lymphocyte transformability could be fortuitous or might indicate a role for cortisol in controlling lymphocyte function in vivo.

Adult↗