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Biomedical subjects

A Milewicz

Publications and source records attributed to A Milewicz.

At least 19 recordsLinked to original sources
PubMed1992

Tissue androgens and the endocrine autonomy of breast cancer.

To evaluate whether a tumour-directed gradient in androgen levels in fatty tissue can account for the maintenance of intra-tissue oestradiol levels, androstenedione (Adione), dehydroepiandrosterone (DHEA), testosterone (Testo) and androstenediol (Adiol) were assayed in breast tumour tissues and in fatty tissue taken at different distances from the tumour. The concentration of Adione was significantly lower in tumour tissue (5.6 +/- 1.5 pmol/g tissue; mean +/- SEM; n = 14) than in the adjacent fatty tissue (20.4 +/- 2.2; P less than 0.005). Testo, by contrast, occurred in equal concentrations in tumour (0.80 +/- 0.11) and in adjacent fatty tissue (0.70 +/- 0.07). Adione levels tended to be lower after the menopause only in fatty tissue, not in the tumour tissue; for Testo no differences were observed between samples from pre- and postmenopausal patients. Tumour DHEA levels (57 +/- 12 pmol/g tissue) were lower than those in fatty tissue (117 +/- 17; P less than 0.02). As with Adione, fatty tissue DHEA concentrations tended to be higher in pre- than in postmenopausal patients. Adiol showed a similar pattern as Testo. For none of the aromatase substrates nor their precursors a tumour-directed gradient was observed. The concentration of Adione in breast cancer tissue is much lower than the reported Km of the aromatase system for Adione. We have concluded, therefore, that the maintenance of oestradiol concentrations in tumour tissues is not substrate-driven.

Adipose Tissue↗
PubMed1992

On the significance of in situ production of oestrogens in human breast cancer tissue.

We have previously shown that human breast cancer is autonomous in the regulation of its intra-tissue oestradiol concentration. Breast fatty tissue does not have this capacity, but rather reflects changes in the peripheral oestradiol concentration. To further evaluate the relative contribution of breast cancer and fatty tissue to the maintenance of tumour oestradiol we investigated whether a tumour-directed gradient in aromatase activity and oestrogen levels existed in mastectomy specimens. No such gradient was found, however, for aromatase, oestrone, oestradiol and their sulphates. Aromatase activity (expressed per gram of tissue) and the concentrations of oestradiol, oestradiol sulphate and oestrone sulphate were higher in tumour than in breast fatty tissue. Fatty tissue had a higher oestrone concentration. It is tentatively concluded that breast tumour aromatase activity is more important for the maintenance of tumour oestradiol levels than aromatase in breast fatty tissue.

Adipose Tissue↗
PubMed1992

Estrogens in plasma and fatty tissue from breast cancer patients and women undergoing surgery for non-oncological reasons.

Breast cancer tissue is able to maintain the tissue estradiol level in spite of the massive decrease in plasma estradiol associated with menopause, whereas fatty tissue from breasts with malignancies more closely reflects the changes in plasma. In the present study estrone and estradiol levels in fatty tissues from different origins were compared to evaluate the capacity of distant fatty tissues to act as estrogen reservoirs. Abdominal fat was obtained from 25 premenopausal and 20 postmenopausal women who underwent surgery for non-oncological reasons. Estrone and estradiol levels in these tissues were compared to those in breast fatty tissue from breast cancer patients. Plasma estrogen levels were not different in the two groups. In both groups, median plasma estradiol levels dropped sharply with menopause (from 363 to 40 pmol/l in breast cancer patients; from 280 to 45 pmol/l in the non-oncological patients; p less than 0.002), whereas a significant decrease in plasma estrone was observed only in the breast cancer patients (from 238 to 140 pmol/l; p less than 0.02). In premenopausal women, median estrone and estradiol levels in breast fatty tissue (1135 and 375 fmol/g, respectively) and abdominal tissue (1390 and 470 fmol/g, respectively) were not different. In postmenopausal women, however, significantly higher estrone levels (663 vs. 508 fmol/g; p less than 0.01) and estradiol levels (245 vs. 187 fmol/g; p less than 0.02) were found in abdominal fatty tissue. In view of the absolute estrogen levels in breast and abdominal fatty tissue and in plasma, we conclude, however, that it is unlikely that remote fat contributes substantially to the maintenance of estrogen levels in breast cancer tissue.

Abdomen↗
PubMed1992

[Effect of oestro-feminal on lipid metabolism in postmenopausal women].

The cessation of hormonal function of ovaries after menopause leads, among others, to changes of concentration of serum lipids and lipoproteins which may cause an increased risk for atherosclerosis. The purpose of the study was an evaluation of the effect of three- and six-month use of conjugated oestrogens on lipid metabolism in women after surgically induced menopause. Both after three and six months of treatment a reduction of intensity or abolition was found of the climacteric syndrome symptoms. After six months of substitutive therapy beneficial changes were observed in lipid metabolism (decrease of total and LDL-cholesterol levels, and increase of HDL-cholesterol level). Hormonal therapy may play a protective role and prevent the development of atherosclerosis in women after menopause.

Adult↗
PubMed1992

[Importance of prolactin level indication in detection of Sheehan syndrome].

Prolactin (PRL) levels were studied in 5 women with Sheehan syndrome before and after metoclopramide (MCP, 10 mg i.v.) and domperidone (MOT, 10 mg i.v.) stimulation. The levels of PRL were measured by RIA method. The obtained results were compared with control group (10 female volunteers). Decreased serum level of PRL was found in 3 women before stimulation in comparison with control group. The highest serum concentration of PRL was found 30 min after MOT and MCP injection. In group of women with Sheehan syndrome the level of PRL was not significantly increased in MCP-test. In MOT-test the level of this hormone did not change. The findings of the present investigation suggest that measurement of PRL serum levels in MOT-test could be of value in early diagnosis of Sheehan syndrome.

Adult↗
PubMed1991

Liver transplantation in children.

Although liver transplantation is now accepted as the ideal therapy for end-stage liver disease, relatively few centers have gained a large experience in children, and good results have been elusive. Technical difficulty and a high incidence of graft failure are among the obstacles to success. At the University of California at Los Angeles, 39% of our liver transplants are in the patients who are younger than 18 years. We have analyzed our experience with 103 patients to emphasize factors important to a favorable outcome with the procedure. One hundred twenty-three transplants were performed in 103 children (mean age, 5.2 years; 48% younger than 3 years). No reduced-size grafts were used. Scrupulous attention to technical details of the vascular reconstruction, including frequent use of the supraceliac aorta of the recipient and interrupted suture techniques, ensured construction of sound hepatic artery and portal vein anastomoses at the first operation. Preoperative exchange transfusions were used if the prothrombin time was prolonged beyond 7 seconds, resulting in an average blood loss of only 3.3 volumes. Cyclosporine dosage was maintained in the high therapeutic range for the first 4 weeks, and anti-T-cell antibody (OKT3) was used for rejection (38%). Amphotericin prophylaxis was used for biliary atresia patients with multiple previous operations. Eighty-two of one hundred three patients (80%) are alive. There were no intraoperative deaths. Actuarial survival rates at 6 months, 1 year, and 5 years are 80%, 79%, and 77%, respectively. Survival of patients who underwent transplantation at age less than 1 year is 65% versus 85% at age more than 1 year (p = 0.08). Retransplantation was performed in 19 patients (18%), with a survival rate of 58%. Hepatic artery thrombosis, the most frequent technical complication, occurred in only 16 patients (13%). Survival rates of ABO identical-match versus nonidentical-match grafts were 96% and 60%, respectively (p = 0.02). Graft survival was only 47% if more than one steroid cycle was needed, compared to 75% survival with OKT3 treatment. Despite impairment of renal function (glomerular filtration rate [GFR] less than 80 cc/kg/min) in 54% of patients and hypertension requiring therapy in 27%, 90% of the children demonstrated enhancement of growth, development, and functional status. The following conclusions were made. (1) Pediatric liver transplantation is the treatment of choice for all types of end-stage liver disease and should be considered early. (2) Factors that enhance survival include technical precision, aggressive retransplantation, antifungal chemoprophylaxis and therapy, and judicious immunosuppression with use of OKT3 for rejection.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1991

Lipid disturbances in women with polycystic ovary syndrome.

Small but detectable disturbances concerning blood lipid levels manifested by somewhat higher concentrations of LDL-cholesterol and triglycerides as well as higher values of atherogenic indices expressing the ratio of cholesterol present in atherogenic lipoprotein fractions to that present in atheroprotective HDL fraction have been shown to exist in 36 women with polycystic ovary syndrome. HDL-cholesterol concentration was lower in women with polycystic ovary syndrome than in healthy women. The disturbances described above were more pronounced in obese patients. No correlation was found between the disturbances in lipid levels and hormonal disturbances particularly hyperandrogenemia.

Adult↗
PubMed1985

Combined 21- and 11 beta-hydroxylase deficiency in familial congenital adrenal hyperplasia.

Studies in three families (A, B, and C) revealed five patients with congenital adrenal hyperplasia (CAH) due to partial and combined 21- and 11 beta-hydroxylase deficiency. One patient (A-11 1), a 23-yr-old severely virilized chromosomal female, was reared as a male, and two females (B-11 2 and C-1) complained only of hirsutism, acne, and menstrual abnormalities. Patients A-11 2 and B-11 8 (17 1/2 and 10 yr old) were asymptomatic and detected by finding an HLA genotype identical to that of their respectively affected brother and sister. Three patients (A-11 1, A-11 2, and C-1) had moderate hypertension. In spite of the wide range of clinical manifestations, all individuals had elevated androgen levels, while cortisol secretion was severely impaired only in A-11 2. 21-Hydroxylase deficiency was diagnosed on the basis of markedly increased plasma and urinary levels of 17-hydroxyprogesterone (17-OHP) and 21-deoxycortisol and their respective urinary metabolites pregnanetriol and pregnanetriolone. PRA was elevated in three patients, while urinary aldosterone was normal or increased. 11 beta-Hydroxylase deficiency was diagnosed on the basis of increased 11-deoxycortisol and deoxycorticosterone in plasma and tetrahydro-11-deoxycortisol and deoxycorticosterone in urine, particularly after ACTH administration. In contrast to classical 11 beta-hydroxylase deficiency CAH, urinary 18-hydroxycorticosterone and 18-hydroxy-11-deoxycorticosterone were normal or elevated. The nature and mechanism of a combined enzymatic defect are unknown. The coincidental presence in a single individual of the mutant genes for both 21- and 11 beta-hydroxylase deficiency CAH is very unlikely to occur. Two alternative hypotheses may explain our findings. One is the existence of a genetically inherited abnormal (or aberrant) 11 beta-hydroxylase, whose affinity for its normal substrate is changed for an abnormal one (17-OHP). As a result, 11 beta-hydroxylation of 11-deoxycortisol is deficient while 17-OHP 11 beta-hydroxylation is markedly enhanced. Thus, both 11-deoxycortisol and 21-deoxycortisol as well as their urinary metabolites accumulate. The ability for 18-hydroxylation, however, remains normal. In this case, 21-hydroxylase is not deficient, yet 21-deoxycortisol cannot be further hydroxylated to cortisol, since this steroid is not a suitable substrate for the enzyme. Such a disorder may represent a new allelic variant of 11 beta-hydroxylase deficiency CAH, which, similar to 21-hydroxylase deficiency, is completely linked to the HLA complex.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Hyperplasia, Congenital↗
PubMed1985

The effect of treatment with defined spleen dialysate on plasma levels of 21-deoxycortisol and 17-hydroxyprogesterone in women with polycystic ovary disease.

Based upon the use of a specific radioimmunoassay method, the plasma levels of 21-deoxycortisol (21-DF) as well as of 17-hydroxyprogesterone (17- OHP) were examined in women with polycystic ovary disease - in normal conditions and after stimulation with corticotropin and chorionic gonadotrophin. It was shown that there was an increased level of 21-DF in women with PCOD in comparison with the control group, both in normal conditions and after ACTH stimulation. Besides there was a pathological increase in the level of 21-DF after HCG stimulation, which was not observed in the control group. These results suggest an enzymatic defect ("11-aberrant hydroxylation") in PCOD, which is due to a disturbance of steroidogenesis. Based upon the positive experiences with a defined spleen dialysate ("DSD", Solcosplen) in the treatment of climacteric discomforts and its known influence on steroidogenesis, we examined possible effects on the levels of 21-DF in females with PCOD. The decrease in the level of this steroid was associated with bleeding in women with amenorrhea. This shows the importance of 21-DF in the pathogenesis of PCOD and proves the efficacy of the spleen dialysate in women suffering from this disease.

17-Hydroxycorticosteroids↗