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Biomedical subjects

S R Kottegoda

Publications and source records attributed to S R Kottegoda.

At least 19 recordsLinked to original sources

Comparison of AFP and beta-hCG levels in infiltrating duct mammary carcinoma at different stages of malignancy.

In order to assess the likely clinical value of AFP and beta-hCG levels as markers of the extent of spread of infiltrating duct mammary carcinoma, we compared (Mann-Whitney U test) the immunoreactive tumour tissue concentrations of the respective antigens, measured by specific RIA, after mastectomy in Chinese women at stages I (n = 9), II (n = 13) and III (n = 7) with that of normal breast tissue (n = 11). Elevated concentrations of the oncofetal antigens were found at all stages of malignancy. The discovery of an hCG-like material in the extract of normal breast tissues indicates limited value of beta-hCG assay in mammary tumours. However, our findings generally suggest that measurement of the tumour tissue AFP levels warrant consideration as a useful biochemical marker for in-vitro evaluation of tumour spread at all stages of malignancy.

Adult↗

Effect of indomethacin on the injection-abortion interval of 15(S) 15 methyl PGF2 alpha-induced mid-trimester abortions--a randomized study.

There have been conflicting reports on the effect of non-steroidal anti-inflammatory drugs on the abortifacient effect of prostaglandins. The efficacy of intra-amniotic 1.5 mg 15(S) 15 methyl PGF2 alpha (15 me PGF2 alpha) in terminating mid-trimester pregnancy in 10 subjects has been compared with the effect of the same medication given to 10 others who had had indomethacin 25 mg and 50 mg orally three and one hour before the PG administration. In the subjects who had the PG analogue only the injection-abortion interval was 17.0 hours. This was significantly shorter (P less than 0.01) than in those who had also received indomethacin (25.4 hours).

Abortifacient Agents↗

alpha-Fetoprotein levels in fullterm and very low birthweight infants.

Plasma alpha-fetoprotein (alpha-FP) levels were determined in fullterm and very low birthweight (VLBW) infants in the first week of life and serially in a cohort of VLBW infants for the first 24 weeks after delivery. A rapid decline in alpha-FP levels was observed in both the fullterm and VLBW infants initially. Beyond 2 weeks of age, there was a gradual, linear decline until 6 weeks, followed by a more rapid period of decline from 6 to 16 weeks. The decline in the ensuing weeks demonstrated an asymptotic pattern. The half-life of alpha-FP was 7.5 days in the first week of life in both fullterm and preterm infants, 28.7 days from 2 to 6 weeks of life and 11.9 days from 6 to 16 weeks of life in VLBW infants.

Female↗

Effect of a beta-adrenoceptor antagonist, pindolol, on human uterine smooth muscle.

The effect of a beta-adrenoceptor antagonist, pindolol, on uterine smooth muscle in term pregnant women was studied in vitro and in vivo (in hypertensive women). In most preparations in vitro and in most patients in vivo, the drug induced an inhibitory effect on spontaneous uterine activity. The fetal heart rate was not affected by the drug. These actions of pindolol would make it an appropriate drug in the therapy of hypertension in pregnancy.

Adult↗

Geriatric gynaecology.

The menopause is the physiologic cessation of normal, cyclic ovarian function. The development of vasomotor symptoms, atrophic changes in the genito-urinary system and osteoporosis are associated with oestrogen deficiency. Osteoporosis is the most important consequence of ovarian failure because it causes considerable morbidity and mortality. There is no simple screening test for detecting postmenopausal women who are at risk of developing osteoporosis. Oestrogen replacement therapy affects lipid metabolism and may be associated with the risk of developing endometrial cancer, breast cancer and thromboembolic disease. The addition of a progestogen regime have shown to reduce the risk of endometrial pathology. The most consistent and beneficial effect of oestrogen is the prevention of osteoporosis and subsequent fractures. Non-hormonal treatment regimes for postmenopausal osteoporosis include calcium, calcitonin and 1-alpha hydroxyvitamin D. It may be possible to use hormonal treatment for the optimal control of menopausal symptoms and non-hormonal treatment as long term prophylaxis.

Aged↗

A comparative study of peritoneal fluid concentrations of oestradiol-17 beta, progesterone, and testosterone in controls and in patients with endometriosis.

To ascertain whether a cyclical variation exists in the steroid hormone concentration of the peritoneal fluid between controls and patients with endometriosis, we set out to measure the concentration of oestradiol--17 beta (E2), progesterone (P4), and testosterone (T) by specific radioimmunoassay in the peritoneal fluid of these 2 groups. Forty six patients (mean age, 30.1 +/- 6 years) with pelvic endometriosis and 32 control patients (mean age, 32.2 + 3.8 years) without endometriosis were studied. The significance of differences between groups was determined by the Mann-Whitney mu test. In the control group a significant rise in peritoneal fluid E2 (P = 0.017) and P4 (P = 0.048) levels was observed in the luteal phase compared to the follicular phase, but no such difference was noted in women with endometriosis. It is suggested that peritoneal fluid steroid hormone assays are not helpful in the evaluation of ovarian function in endometriosis.

Adult↗

Histopathology of the testes from male transsexuals on oestrogen therapy.

This study was conducted to determine whether the histopathology of the testis of the male transsexual would throw light on the pathogenesis of male transsexualism. Histological sections of testicular tissues obtained at sex reassignment surgery from phenotypic male transsexuals (n = 10, age 21-33 years) with XY sex chromosome constitution were studied by light microscopy. The patients were diagnosed on clinical and psychiatric evidence and had been on oestrogen therapy for 6-13 years. The significant histological findings in the ten subjects were: (i) Focal or normal spermatogenic activity associated with normal Leydig cell population in three cases, and (ii) Total absence of spermatogenic activity associated with reduced Leydig cell population in seven cases. We suggest that the observed histological features are due to refractoriness to oestrogen, and the iatrogenic effects of oestrogen superimposed on normal or altered hypoathalamo-pituitary function.

Adult↗

Elevated intravesicular fluid thyroid-stimulating hormone concentration in hydatidiform mole.

In an attempt to explain hyperthyroidism in hydatidiform mole, concentrations of immunoreactive thyroid-stimulating hormone (TSH) together with human-chorionic gonadotrophin (beta-hCG) were measured in the serous fluid obtained from 43 patients aged 15-45 years and with amenorrhea 11-31 weeks. Elevated concentrations of these two hormones were found in all samples. It is probable that hyperthyroidism could stem from TSH immunologically similar to pituitary TSH and distinct from hCG and luteinizing hormone (LH) that we have identified in hydatid vesicles.

Adolescent↗

Is vasoactive intestinal polypeptide the principal transmitter involved in human penile erection?

Previous work from this laboratory reported on the effects of several autacoids and other agents on strips of human corpus cavernosum (cc) muscle. These investigations indicated the presence in the cc muscle of a) atropine-sensitive cholinoceptors, b) alpha- and beta-adrenoceptors and c) a non-adrenergic non-cholinergic mechanism. Several recent publications have presented evidence in support of the possibility that vasoactive intestinal polypeptide (VIP) is an important, or the chief, transmitter in human penile erection. This paper describes the actions of VIP and other compounds on the cc muscle and the effect of intracavernous injection of VIP in volunteers. Among the agents tested, VIP was the most potent relaxant of the cc muscle. This effect, which was seen at a dose as low as 0.03 nM, was suppressed by VIP antiserum. The response of the isolated penile vasculature to VIP was similar. VIP antiserum had no effect on the relaxation of the cc muscle produced by field stimulation. In five of the seven subjects given intracavernous VIP (1.0 micrograms.) some degree of penile enlargement was evident, but none had an erection. It is suggested that local release of VIP, withdrawal of the alpha-adrenoceptor mediated tonic supply to the penis and the activation of the latter's beta-adrenoceptors are all probably involved in penile erection in man.

Humans↗

Intrauterine responses to nipple stimulation in late pregnancy.

Characteristics of intrauterine activity in response to nipple stimulation were studied in 9 healthy pregnant subjects at term. All patients showed an increase in uterine activity varying from 10 to 730%. In 1 subject, marked uterine hypertonus was noted which resulted in profound fetal bradycardia. This response was transient, lasting 5.5 min, and fetal outcome unaffected. We believe that nipple stimulation is associated with a higher incidence of increased uterine activity in terms of frequency, intensity and basal tone, than has been previously recognized. This uterine hypertonus may affect the fetal heart rate adversely indicating the need to exercise caution when adopting this manoeuvre in late pregnancy, particularly when there is already evidence of fetal compromise.

Adult↗

Steroidogenic expression of delta 5-3 beta-hydroxy pathway of androgen biosynthesis by human breast carcinoma.

In order to determine whether human mammary tumours could contribute to cholesterol and dehydroepiandrosterone biosynthesis in breast cancer patients, incubations of homogenates of infiltrating ductal carcinoma were carried out separately with 2-14C acetate (patient, n = 6; 21-80 years) and 7n-3H pregnenolone (patient, n = 5, 36-74 years) as substrates. With the aid of the reverse-isotope dilution technique, 14C cholesterol and 3H dehydroepiandrosterone were characterized; these two gave maximum yields of 2.38 X 10(-4)% and 9.42 X 10(-2)% respectively. These results indicate that there exists a potential for the synthesis of cholesterol and dehydroepiandrosterone in vivo. It is suggested that the biosynthetic pathway involved in the synthesis of the latter is; acetyl CoA----cholesterol----pregnenolone----17 alpha-hydroxypregnenolone----dehydroepiandrosterone.

17-alpha-Hydroxypregnenolone↗

Oxytocinase activity in human amniotic fluid and its relationship to gestational age.

Oxytocinase (EC 3.4.11.3) activity in amniotic fluid samples obtained from 200 normal pregnant women (mean age, 28 years) between 14 and 40 weeks of gestation and during active labor was assayed using S-benzyl-L-cysteine-p-nitroanilide (BCN) and L-leucine-p-nitroanilide (LN) separately as substrates. With both substrates, amniotic fluid oxytocinase activity correlated inversely with gestational age; the level of the enzyme, which was highest in early pregnancy, decreased exponentially to a minimum near term and during labor. However, whether oxytocinase activity in the amniotic fluid is of any significance for the maintenance and/or termination of pregnancy remains to be established.

Aminopeptidases↗

Prostaglandins, not cyclic GMP, inhibit oxytocinase isoenzymes from human amniotic fluid in vitro.

Two isoenzymes of oxytocinase (EC 3.4.11.3) activity were fractionated from human amniotic fluid samples between the 14th and 22nd weeks of gestation by Ultrogel acrylamide-agarose gel filtration and partially characterized. The isoenzymes were competitively inhibited by PGE1, PGE2 and PGF2 alpha more at pH 6.2 than at pH 6.8, whereas cyclic GMP (cGMP) and its 8-bromo derivative had no effect at either pH. The implications of these findings are discussed and it is suggested that since the activity of amniotic fluid oxytocinases is very low or minimal at or near term, inhibition of these by prostaglandins may not have physiological significance in the initiation of human parturition.

Aminopeptidases↗

Plasma levels of 13,14-dihydro-15-keto PGE2 after vaginal application of a new PGE2 film.

To determine the release and absorption profile of prostaglandin E2 from a new vaginal film formulation containing 850 micrograms PGE2, serial plasma levels of 13,14-dihydro-15-keto PGE2 were measured by radioimmunoassay in pregnant women between 16 and 18 weeks gestation. A control group, using placebo vaginal film was included in the study. There was a somewhat uniform increase in the plasma levels of the PGE2 metabolite, reaching peak levels between 4 and 6 hours after application of the film. The findings suggest that this drug formulation could be used clinically when slow constant release of the prostaglandin is required over a period of hours such as in pre-induction cervical ripening of term pregnancy.

Abortion, Induced↗