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Biomedical subjects

M W Ghilchik

Publications and source records attributed to M W Ghilchik.

67 records · Page 4Linked to original sources
PubMed1971

Insulin response to glucose in patients with peripheral vascular disease, arteritis, and Raynaud's phenomenon.

Twenty-three patients with peripheral vascular disease due to atheromatous blocks in large vessels, four patients with arteritis, and twenty patients with Raynaud's phenomenon were tested for insulin response to glucose. (In an earlier investigation patients with small-vessel peripheral vascular disease did not secrete insulin in response to a glucose load--a previously unreported finding.) Insulin output after glucose in patients with atheromatous blocks in large peripheral arteries fell into three categories: (1) normal glucose tolerance and insulin output, the insulin rise (peak/basal ratio) comparing well with the rise in controls; (2) carbohydrate intolerance with a prediabetic pattern of glucose-tolerance test, and raised circulating insulin levels both fasting insulin and after glucose, so that the insulin rise was lower than normal; or (3) the flat insulin responses after glucose that had been noted in small-vessel disease with normal glucose tolerance. Thus in these twenty-three patients with large-vessel blocks presenting with peripheral vascular disease the high and late insulin secretion after glucose reported by other workers for patients with atheroma could not be confirmed. High but not delayed insulin peaks were seen after a glucose stimulus in some patients with arteritis and with Raynaud's phenomenon.

Adolescent↗
PubMedDate not supplied

Aromatase activity in normal breast and breast tumor tissues: in vivo and in vitro studies.

Infusions of isotopically labeled [3H] androstenedione with measurement of [3H] estrone in normal breast and breast tumor tissue have been carried out in an attempt to determine the contribution that aromatization makes to the estrogen content of breast tissues. After infusion of [3H] androstenedione for 12h there was significant uptake of this steroid by normal breast and breast tumors. [3H] Estrone was detected in all samples of normal breast tissue examined so far but not in all tumors. Aromatase activity when measured in vitro was found to be higher in breast tumors than in fat next to the tumor or normal breast fat. Studies in which we have examined the effect of epidermal growth factor on aromatase activity in cultured breast adipose tissue suggests that the response may be influenced by a subject's menopausal status. Results from these preliminary studies suggest that the aromatization of androgens may make a significant contribution towards the estrogen content of some breast tumors and that growth factors may also be involved in regulating aromatase activity.

Adipose Tissue↗
PubMedDate not supplied

The effect of oestrogens and medroxyprogesterone acetate on the uptake of cytotoxic drugs by MCF-7 breast cancer cells.

Previous studies have shown that human breast cancer cells (MCF-7) show an increased response to a number of cytotoxic drugs after 48 h pretreatment with medroxyprogesterone acetate (MPA). As there is evidence that MPA can influence membrane fluidity, we have examined the effect of pre-treatment with MPA on the uptake of methotrexate (MTX) and vincristine (VCR) by MCF-7 cells. The effect of pre-treatment with oestrogen on cytotoxic drug uptake was also examined. After 48 h pre-treatment with MPA (40 or 160 nmol/L), the uptake of MTX was significantly reduced by 14%-44%. Uptake of VCR was also reduced (10%-16%) after pre-treatment of cells with MPA but to a lesser degree than detected for MTX. Pre-treatment with ethinyloestradiol increased the uptake of MTX by up to 45% but enhanced uptake was only detected in cells after exposure to MTX for 1 h. While the results from this study show that oestrogens or MPA can alter the uptake of cytotoxic drugs by MCF-7 breast cancer cells, it is not clear how the MPA dependent decrease in drug uptake enhances the response of MCF-7 to such drugs previously reported.

Antineoplastic Agents↗
PubMedDate not supplied

Oestradiol and epidermal growth factor in breast cyst fluid.

Gross cystic breast disease may be categorised into 2 groups according to the intracystic cation ratios (Na+/K+ less than 3 and Na+/K+ greater than 3). It has been suggested that women in the low electrolyte ratio group may be at higher risk of developing breast cancer. Epidermal growth factor concentrations in breast cyst fluid were significantly higher in the low than in the high electrolyte ratio group but there was no significant difference in oestradiol concentrations between the two groups of breast cysts. A negative correlation was obtained between intracystic concentrations of epidermal growth factor and Na+/K+ (rs = -0.617, p less than 0.001). No evidence was found to support the hypothesis that concentrations of epidermal growth factor may be modulated by oestradiol. The higher concentrations of epidermal growth factor in the low electrolyte ratio group may provide an explanation for the higher risk of breast cancer observed in this group.

Biomarkers↗
PubMedDate not supplied

The effect of ethynyloestradiol and medroxyprogesterone acetate on the in vivo uptake and metabolism of 3H-oestradiol by breast tumour tissue in postmenopausal women.

The uptake and metabolism of 3H-oestradiol by breast tumour tissue was studied in three postmenopausal women before, after 1 week of treatment with ethynyl-oestradiol (EE, 10 micrograms/day) and again two weeks later after treatment with medroxyprogesterone acetate (MPA, 500mg/day, i.m.). Treatment with EE reduced the tissue: plasma gradients for both 3H-oestradiol and 3H-oestrone and little further change in these ratios occurred after MPA treatment. The proportion of oestrogen present as 3H-oestrone increased in tumours from 2/3 women after treatment with MPA but not EE, although no increase in the activity of oestradiol 17 beta-hydroxysteroid dehydrogenase (E2DH) was detected. Plasma and tissue concentrations of 5-androstenediol, dehydroepiandrosterone and dehydroepiandrosterone sulphate were all reduced after MPA treatment. The results from this study show that treatment with EE and MPA can reduce the uptake of oestradiol by breast tumours. No increase in E2DH activity was detected but it is possible that MPA influences other enzymes involved in oestradiol metabolism.

17-Hydroxysteroid Dehydrogenases↗
PubMedDate not supplied

Oestrone sulphatase activity in normal and malignant breast tissues: relationship with tumour location.

The hydrolysis of oestrone sulphate to oestrone, by oestrone sulphatase, is thought to be the major source of the high oestrogen concentrations which are present in breast tumours. In this study, the possibility that the location of the tumour within the breast or the size of the tumour might influence oestrone sulphatase activity has been examined. Normal and malignant breast tissues were obtained from 2 pre- and 9 post-menopausal women after mastectomy. Oestrone sulphatase activity was measured in microsomes prepared from these tissues and related to the location and size of the tumour. Of the 11 mastectomy specimens examined, 4 of the 11 (36%) quadrants bearing the tumour had the highest oestrone sulphatase activity. No significant difference in oestrone sulphatase activity was detected between normal and malignant tissues. No significant relationships were found between tumour sulphatase activity and activity in the quadrant bearing the tumour or tumour size and tumour oestrone sulphatase activity. The detection of the highest oestrone sulphatase activity in 36% of the breast quadrants bearing a tumour, or on which a tumour impinged, which a tumour impinges, while lending some support to the concept that breast tumours produce factors which are able to influence the activity of this enzyme, suggests that it is to a lesser extent than previously reported for the aromatase.

Adult↗
PubMedDate not supplied

Breast haematomas: same appearance, different diagnosis.

We report two cases of patients presenting as breast haematomas but with uncommon underlying pathology. One patient had a bilateral breast augmentation by a peculiar method of inserting shredded cellophane packing. A haematoma developed after a fall and subsequently became infected. The second patient was on long-term anticoagulant therapy and developed a haematoma through bleeding from an occult malignant lesion. Both cases demonstrate the need to obtain histology--especially in the elderly, where history and clinical examination may confound diagnosis.

Breast Diseases↗
PubMedDate not supplied

The effect of treatment with 4-hydroxyandrostenedione or medroxyprogesterone acetate on human breast tumour regression.

We have assessed cell deletion in breast tumours removed surgically from postmenopausal women by measuring the distribution ratio of acid phosphatase activity between the bound (in the lysosome) and free (in the phagosome) states. In benign breast tumours the acid phosphatase distribution ratio was much higher than that found in untreated malignant breast tumours. The acid phosphatase distribution ratio was also measured before and after treatment in malignant breast tumours removed from eight patients treated with 4-hydroxyandrostenedione (4-OH A) and in six patients treated with medroxyprogesterone acetate (MPA). Elevated acid phosphatase distribution ratios in benign compared with malignant tumours, and in malignant tumours after treatment from four of eight patients treated with 4-OH A and from three of six patients treated with MPA, may suggest higher cell deletion in these patients.

Acid Phosphatase↗