Cytochemical demonstration of steroid binding in human ovarian carcinoma and thecofibroma. A preliminary report.
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Biomedical subjects
Publications and source records attributed to S Kullander.
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In a randomized, single-blind study, of a pilot nature, the administration of terbutaline sulphate was found to cause significant inhibition of contractions in premature labor. This effect became evident within 30 min when the dosage was 0.1 mg in 1 ml cellulose gel, applied vaginally, and within 2 h when released from a 5-g medicated vaginal polymer ring containing 10% terbutaline sulphate. No generalized effects of the terbutaline were noted (such as increased blood pressure or tachycardia) and the level of terbutaline in peripheral venous blood remained low. Vaginally administered terbutaline can obviously be quickly resorbed, giving a localized effect. Thus applied, terbutaline would appear to offer a number of advantages as regards treatment procedure.
In a histologic study of human endometrium transplanted into nude mice, eutopic endometrium from each of 8 women was transplanted subcutaneously to 4 nude mice, 1 of which was treated with polyestradiol phosphate, 1 with MPA, 1 with danazol, and 1 of which was left untreated as a control. Grafts were removed after varying intervals of up to 57 days. Residual histologically evaluable endometrial tissue was found in 32 of the 96 grafts (33%). None of the extirpated grafts had the same histologic pattern as the eutopic endometrium. Besides confirming that human endometrium can be transplanted into nude mice, our findings suggest that grafts react histologically in the same way as eutopic human endometrium to hormone treatment. The specific stroma seems to be crucial to a graft's capacity to respond to hormonal stimuli, and its replacement by fibrous tissue was accompanied by glandular epithelial changes very similar to those seen in human endometriotic lesions.
In a study of the morphologic effects of various steroid hormones on human uterine endometrium and endometriotic tissue, specimens from 6 women were transplanted subcutaneously into 24 nude mice. In each case, specimens collected simultaneously were transplanted to 4 mice, endometrium to one lateral abdominal wall and endometriotic tissue to the other. All mice were given polyestradiol phosphate subcutaneously the first day after operation. After a 2-week interval, of each 4 mice, 1 mouse was given polyestradiol phosphate, 1 medroxyprogesterone acetate, 1 danazol, and 1 no further injections. This treatment continued for 8 weeks, after which the mice were killed and the grafts extirpated. Histologic changes in the grafts varied according to the treatment schedule but were very similar in both types of tissue. Our findings suggest that histologic differences between endometrium and endometriotic tissue seen under natural conditions may, at least partly, be due to variations in environmental factors.
In our in vitro fertilization program, only clomiphene/human chorionic gonadotropin-stimulated cycles have been used, yielding 1.6 preovulatory oocytes/woman at follicle aspiration. The cleavage rate was significantly influenced by the percentage of abnormal spermatozoa and by the percentage of motile spermatozoa in the spermiograms. At embryo replacement, a tilted uterus obtained by a full bladder in the woman simplifies the replacement procedure. In the last 12 months, 47 embryo transfers have been carried out, resulting in five clinical pregnancies. Of these pregnancies, one has proceeded to term, one resulted in a miscarriage, and three resulted in ectopic pregnancies.
High concentrations of immunoreactive trypsin (IRT) in the blood, and low concentrations of trypsin activity in fecal specimens have been found in newborn infants with cystic fibrosis (CF). The amniotic fluid concentrations of IRT and of IRT in complex with alpha 1-antitrypsin (alpha 1AT) were studied in 39 samples taken in about the 17th gestational week, and in 7 samples taken because the mothers had previously given birth to children with CF. The midtrimester samples contained trypsin in complex with alpha 1AT in a concentration of 30-200 micrograms/liter, and small amounts of trypsinogen, 0-50 micrograms/liter. Three of four amniotic fluid samples from CF fetuses had very low concentrations of trypsin in complex with alpha 1AT (less than 10 micrograms/liter), and only small amounts of trypsinogen (less than 10 micrograms/liter). Further prospective studies are needed to ascertain whether the determination of IRT in amniotic fluid may be of use in prenatal diagnosis of CF.
Normal human placenta and amnion from the 20th week of pregnancy were transplanted into nude mice. The transplants retained the histological and immunohistochemical picture of the original tissue and maintained synthesis of human chorionic gonadotropin (hCG), pregnancy-specific beta 1-glycoprotein (SP1), GnRH and placental proteins PP5, PP11 and PP12 for 5 weeks. This experimental model has a wide potential application for studies on placental protein synthesis and the hormonal influence of human placenta on other simultaneously transplanted human tissues.
Since January 1, 1974, 43,000 routine ultrasound examinations have been performed on 22,400 pregnant women in the Department of Obstetrics and Gynecology, Malmö General Hospital. At the present time, one examination is performed in the seventeenth week of pregnancy and one in thirty-third week. At the first examination, the number of fetuses, fetal anatomy, cardiac activity, and placental site are indicated. Fetometry is performed. Gestational age is adjusted according to the value of the biparietal diameter. The second ultrasound examination is aimed at detecting fetal growth deviations and malformations. In 15% of all pregnancies, ultrasound corrected gestational age by more than 14 days. Ultrasound appeared to be superior to the clinical assessment in 88% of these discrepant pregnancies in predicting date of delivery. The early examination detected 98% of the twin pregnancies, with no false positive results. If an ultrasound examination had been performed within 3 weeks of delivery, 92% of the fetuses with growth retardation were detected. Altogether, the program detected 60% of the growth-retarded fetuses. In 0.4% of the examinations, malformations were detected (0.6% during the last 2 years). A cost-benefit analysis suggested that large economical gains are to be realized by screening. However, organizational and educational problems must be properly solved before general screening is offered to a healthy pregnant population.
Fetal ultrasound combined with semiquantitative measurements of alpha-fetoprotein in maternal serum was used for early detection of neural tube defects and omphalocele in 10 147 pregnancies. The accurate assessment of gestational age, obtained by ultrasound, facilitated evaluation of alpha-fetoprotein concentrations in selecting cases for amniocentesis. The advantage of screening with two independent methods is suggested by the finding that eight out of 10 cases with malformations (spina bifida, encephalocele, anencephalus, omphalocele) were detected when both methods were used. Screening by routine ultrasound alone detected only four malformations and by measurement of alpha-fetoprotein alone only seven. The results suggest that, in a low risk population, ultrasound should be combined with the measurement of alpha-fetoprotein in screening for neural tube defects. Measurement of alpha-fetoprotein is indispensable in detection of the small neural tube defects, where the fetus would survive with severe sequelae. The semi-quantitative analysis of alpha-fetoprotein that may be used in combination with ultrasound examination is of negligible cost.
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Seventeen infertile patients were stimulated with clomiphene citrate and human chorionic gonadotrophin (hCG). During laparotomy or laparoscopy, follicles were aspirated. At least one fertilizable oocyte was obtained from 13 patients, who had normal preovulatory plasma 17 beta-estradiol (mean 2.2 nmol/l) in contrast to the 4 patients with infertilizable oocytes (mean 0.4 nmol/l). A close association was found between the success rate of fertilization and the increment of plasma progesterone from the day before to the day after the operation. If the concentrations of 17 beta-estradiol and progesterone in follicular fluid were below an arbitrary limit (17 beta-estradiol less than 500 nmol/l in association with progesterone less than 2,000 nmol/l), no oocytes could be fertilized. Apparently aspiration of oocytes and follicular fluid did not disturb ovarian steroid production during the luteal phase. The results suggest that plasma 17 beta-estradiol and progesterone determinations may serve as useful predictors for oocyte fertilizability in an in vitro system, following clomiphene-hCG stimulation and multiple oocyte recovery.
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In a double-blind cross-over study the effect of terbutaline spray (Bricanyl aerosol) inhalations was tested in 14 women with severe dysmenorrhea. A significant relief was noted in association with an increased menstrual blood loss. The side effects were few.
ER and PR were assayed in 13 malignant and 20 benign ovarian tumors of different histologic types. ER was detectable in 67% and PR in 40% of the malignant tumors, compared with 35 and 45% in the benign tumors, respectively. The ER concentration was somewhat higher in the malignant lesions but there was no difference in the PR level. A retrospective review of 39 primary ovarian tumors of different pathologic stages and classes, treated postoperatively with medroxyprogesterone acetate (MPA, Depo-Provera, UpJohn) and in most cases Melphalan, showed a high Karnofsky performance index and good complete and partial response rates. The need for a prospective, controlled study of the role of MPA treatment of malignant ovarian tumors in evident.
Specific localization in vivo of marked, 131I-labelled human chorionic gonadotrophin (HCG) was shown by scintillation counting of different tissues to occur in rat ovarian tumor, but not in human Krukenberg tumor heterografts growing subcutaneously in female nude mice. The ovaries of the mice showed an increased uptake. This model system may be useful for studying gonadotrophin receptors and gonadotrophin dependency of human ovarian tumors. A similar study in menstruating women about to be operated upon because of myoma showed a remarkably high uptake in the corpus luteum, but binding also in ovarian follicles. The increased uptake of the radioactivity observed in the ovaries enabled preliminary scanning. This unique specificity of uptake may offer new possibilities in the diagnosis of ovarian tumors. The general turnover of the 131I-HCG in these women is described and applied to a mathematical model. High relative concentrations of 131I were also seen in urine and saliva.
In a prospective investigation biopsy specimens were obtained of 150 women with primary, untreated endometrial carcinoma for determinination of the content of estrogen and progesterone receptors (E2 and PR). After a varying interval 13 who developed metastases despite routine surgical and radiation therapy received treatment with gestagens. The clinical effect of the hormone was studied for any correlation with the initial content of E2 and PR. Eight of the women (61--71 years) proved E2R positive (greater than 10 fmoles/mg cytosolprotein), 2 had no PR and the remaining 6 had PR in a concentration of 7--892 fmoles/mg cytosolprotein). 7 responded clinically to gestagen therapy (tumors poorly differentiated in 3 and moderately in 4). Five of the women (50--84 years) were E2R negative; they had no PR, they did not respond to gestagen therapy and died after 2--8 months (tumors poorly differentiated in 2 and moderatley in 3). Determination of E2R and PR in endometrial carcinoma appears to be a clinically useful test for predicting whether a patient is likely to respond to treatment with gestagens.