Characterization of the phenotype of smooth muscle cells in human fetal aorta on the basis of ultrastructure, immunofluorescence, and the composition of cytoskeletal and cytocontractile proteins.

The phenotype of smooth muscle cells (SMCs) in the aortic media of 7 human fetuses (14-20 weeks of gestation) was examined with transmission electron microscopy, immunofluorescence microscopy, and gel electrophoresis of the cytoskeletal and cytocontractile proteins. Ultrastructurally, virtually all medial cells were identified as SMCs having a poorly differentiated phenotype with a cytoplasm rich in rough endoplasmic reticulum and organelles, and with only a few myofilaments. All medial cells stained intensely with antibodies to vimentin, but only in a 20-week-old fetus could we find a few SMCs staining with antibodies to desmin. Nor was desmin detectable with SDS gel electrophoresis followed by immunoblotting, while clear bands corresponding to vimentin, myosin, and actin were present. In isoelectric focusing and two-dimensional gel electrophoresis beta-actin was the most prominent of the 3 actin isoforms in all cases. The present results show that SMCs in the media of fetal human aorta have a poorly differentiated phenotype, which morphologically and biochemically resembles that previously described in the aorta of fetal and newborn rat, in the arterial intima after endothelial injury, in atherosclerotic lesions, and after spontaneous modulation of medial SMCs in culture.

Hormonal activity of epithelial ovarian tumours in post-menopausal women.

Concentrations of progesterone and oestradiol in peripheral serum and tumour cyst fluid were measured in 42 post-menopausal women with epithelial ovarian tumours (17 cancer, 6 borderline malignant, 19 benign tumours) and in 19 post-menopausal women without ovarian neoplasms. The hormonal response of the endometrium was assessed, progestogen and oestrogen receptor content in the tumour tissue case recorded, and tumour deoxyribonucleic acid (DNA) ploidy was measured by flow cytometry. No significant differences were found between the mean serum steroid levels in patients with malignant, borderline or benign tumours, but the mean serum levels of oestradiol in patients with malignant or benign ovarian tumours were higher than those in the controls. Endometrial hormonal activity was seen in 19% of the samples studied. Malignant and benign mucinous epithelial tumours were the types most frequently associated with hormonal activity. Increased levels of sex steroids were seen in the cyst fluid of serous malignant and borderline malignant tumours, while benign tumours were inactive. The steroid receptor content of the various tumour types did not vary significantly. Ten (59%) out of 17 ovarian carcinomas were found to be aneuploid and 41% diploid as measured by flow cytometry. No significant differences in serum levels of progesterone and oestradiol were found between aneuploid and diploid ovarian carcinomas. These results contribute to our knowledge of the hormonal activity of epithelial ovarian tumours in post-menopausal women.

Serum lipids in Finnish and Japanese postmenopausal women.

Serum lipids were measured in 30 Finnish and Japanese postmenopausal women. Total cholesterol, HDL cholesterol, LDL cholesterol, apo B and the HDL cholesterol/apo A1 ratio were higher in Finnish than in Japanese women. The LDL cholesterol/apo B and apo A1/apo B ratios were lower in Finns than in Japanese. In serum phospholipids the percentage of arachidonic acid was higher and the percentage of the n - 3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, and the eicosapentaenoic acid/arachidonic acid ratio were lower in Finnish than in Japanese women. No significant correlations were found between serum oestrone levels and lipid parameters.

Decreased serum level of dehydroepiandrosterone sulfate in postmenopausal women with ovarian cancer.

Serum levels of dehydroepiandrosterone sulfate (DHEAS) were measured in 41 postmenopausal women with ovarian tumor (16 with ovarian cancer, 6 with borderline malignant and 19 with benign ovarian tumor) and in 21 postmenopausal women without ovarian neoplasm. Circulating DHEAS levels were significantly lower in patients with ovarian cancer than in women with benign ovarian tumor and in control subjects. Women with advanced ovarian cancer had lower DHEAS levels than those with local ovarian cancer. An age-related decrease in DHEAS levels was noted in the control group, while circulating DHEAS levels were independent of age in the ovarian cancer group. The results indicate the effect of ovarian cancer on this adrenal androgen and the possible presence of ovarian factor in malignant ovarian neoplasm.

Vitamin D deficiency in women with femoral neck fracture.

Calcium (Ca) metabolism, with particular reference to serum vitamin D metabolites, was investigated in 40 women with femoral neck fracture (mean age 77.1 +/- 8.6 yr). All the patients were ambulant before the fracture; eight were long-term geriatric in-patients. Serum total and ionised calcium and serum albumin levels were significantly lower, and serum parathormone (PTH) levels significantly higher in fracture patients than in controls. Both serum 25-OH-D and 1,25-(OH)2D were significantly lower in fracture patients than in controls. We concluded that vitamin D, serum PTH and calcium levels should be checked with greater frequency in patients at high risk for osteoporosis and osteomalacia before they reach the age of 70.

Septate uterus and habitual abortion: a case report illustrating successful outcome of pregnancy after second metroplasty.

A case is reported of a woman with septate uterus who suffered failure of the first metroplasty. This measure was undertaken before any pregnancy; thereafter she had 12 consecutive miscarriages, and repeated hysterograms showed the presence of broad septum. A second metroplasty was performed 12.5 years after the first, and after two miscarriages she conceived and delivered a viable male infant after 32 weeks gestation. The thorough investigations, the indications and the correct technique for metroplasty are discussed, as well as the value of cervical cerclage in patients with malformed uterus. The strict indications and successful choice of technique in metroplasty are stressed as leading to good results after metroplasty.

Peripheral and ovarian venous concentrations of steroid and gonadotropin hormones in postmenopausal women with epithelial ovarian tumors.

Peripheral serum concentrations of estrone (E1), estradiol (E2), testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), cortisol, prolactin, LH, and FSH were measured in 28 postmenopausal women with epithelial ovarian tumors (12 ovarian cancer, 5 borderline malignant, 11 benign neoplasms) and in 15 controls before bilateral salpingo-oophorectomy and 1 and 8 weeks postoperatively. The levels of these hormones were also measured in ovarian venous blood of 15 patients with ovarian tumors. E2 was significantly higher in the tumor group than in controls preoperatively and the levels of E1 and E2 decreased after radical operation. Hormone levels were similar in the benign and malignant tumor groups. Only DHEAS levels in peripheral serum were significantly lower in ovarian cancer patients than in the group with benign neoplasm. This was not the case in testosterone and androstenedione measurements. The measured levels of the hormones in ovarian venous blood were highest in mucinous ovarian tumors. E2 and testosterone levels were higher in mucinous ovarian tumors than in others. LH(hCG)-receptor levels were measured in 24 specimens and none of these showed detectable concentrations of LH(hCG) receptor. The results indicate that of all epithelial tumors mucinous ovarian tumors had hormonal activity most often, and malignancy had no effect on hormonal activity.

Vasopressin and prolactin as stress hormones.

The effect of electric stimulation of the uterine cervix on vasopressin and prolactin secretions was investigated in 16 patients with uterine myomas and/or hypermenorrhea. One month after hysterectomy a similar stimulation was induced near the fornix of the vagina. Particularly the first test also seemed to be a considerable psychic stress for the patients. The stimulation did not cause any significant changes in plasma vasopressin and prolactin concentrations.

Tumour-associated antigen CA 125 in patients with ovarian cancer.

The serum levels of antigen CA 125 expressed by epithelial ovarian carcinoma were measured in 27 postmenopausal women with ovarian tumours and in 16 controls. Increased serum levels of CA 125 were found in nine (75%) out of 12 patients with ovarian cancer; in three with stage I disease levels were not elevated. No significant difference was found in the concentration of CA 125 detected in peripheral or ovarian venous blood. Decreased antigen levels were found 6-30 weeks after radical operation and cytostatic chemotherapy in the ovarian cancer group. The results indicate the value of measuring CA 125 as a tumour marker in the follow-up of ovarian cancer.

Elevated progesterone levels in serum and ovarian venous blood in patients with ovarian tumors.

Peripheral serum concentrations of progesterone were measured in 27 postmenopausal women with malignant, borderline, or benign ovarian tumor and in 10 women without ovarian neoplasm. The progesterone levels were significantly higher in all ovarian tumor groups as compared with the controls. There was no difference between malignant and benign tumors. Patients with a tumor volume over 1 000 ml had higher progesterone levels than patients with smaller tumors, in both peripheral and ovarian venous blood. Mucinous ovarian tumors were associated with the highest progesterone levels, compared with other histologic types of ovarian tumor. The results indicate that mucinous ovarian tumors are able to secrete progesterone and that the stage of malignancy has no effect on this hormonal activity.

A possible role of vasopressin in the control of ovarian activity.

Simultaneous vasopressin concentrations in the preovulatory follicular fluid and plasma were determined for 12 patients with tubal infertility. Nine of the patients received clomiphene citrate, 100 mg daily, on cycle days 5 through 9. On the 11th day of the cycle, 5000 IU of hCG was given intramuscularly. At laparoscopy the ovarian follicles were aspirated 36 hours after hCG injection. For three patients the follicle aspiration was performed at laparotomy during the 11th-14th days of the normal cycle. In all these cases the vasopressin concentration in plasma exceeded markedly that in the follicular fluid. In the patients undergoing laparoscopy the vasopressin concentration in the follicular fluid was 11.2 +/- 8.2 pg/ml and that in plasma 17.3 +/- 22.0 pg/ml. It is most probable that the hormone enters fluid from the plasma.

Uterine sarcomas.

During 1962-1980, 44 uterine sarcomas were treated at the Department of Obstetrics and Gynaecology of Tampere University Central Hospital. Of the sarcomas, 35 (79%) were leiomyosarcomas, six (14%) endometrial stromal sarcomas and three (7%) endometrial carcinosarcomas. The 5-year survival for patients with leiomyosarcoma was 51 per cent. The 5-year survival rate for the premenopausal patients was 73% and that for postmenopausal patients 20%. The most important prognostic indicator was the gross presentation of the tumor at the time of surgery. Of the 5-year survival patients 94% were of clinical Stage I and of the failed patients 55%, respectively. Rather poor correlation was noted between the mitotic activity and survival rate. Metastases to the lungs were the most common failure pathway. All six patients with endometrial stromal sarcomas died within 25 months after the diagnosis. High oestrogen and progestin receptor concentrations were demonstrated in the endometrial stromal sarcoma.

Primary malignancies of the fallopian tube.

Ten cases of primary adenocarcinoma of the fallopian tube occurring over 23 year period are presented. The mean age of the patients was 61.2 +/- 9.2 years (range 48-77). Eight of the patients were postmenopausal. Abnormal vaginal bleeding was the most common symptom and was present in six patients. A pelvic mass was detected in seven cases. In one of the patients abnormal vaginal cytology was leading to correct diagnosis. The problem of the disease is a late diagnosis. Eight of the ten patients with tubal adenocarcinoma represented clinical Stage III or IV. Four of the patients are alive more than ten years after the diagnosis. A rare case of carcinosarcoma of the fallopian tube is presented. Only 26 such cases have been described in the literature to date. In addition a case of tubal choriocarcinoma is reported.

Relationship of vulvar lichen sclerosus et atrophicus to carcinoma.

Lichen sclerosus et atrophicus was an associated lesion in 16 of 30 (53%) patients with invasive vulvar carcinoma. In one case invasive carcinoma developed in the background of lichen sclerosus et atrophicus. Additionally in one case lichen sclerosus was found at the margin of the carcinoma. Despite the low malignant potential, patients with vulvar lichen sclerosus et atrophicus need long-standing observation and recurrent histologic examinations.

Maternal blood haemostatic-fibrinolytic balance and intrauterine growth retardation.

In order to study the association between haemostatic-fibrinolytic balance during late pregnancy and retarded foetal growth, 22 mothers with suspected intrauterine growth retardation were studied by blood haematocrit and platelet count, plasma fibrinogen and serum fibrinogen degenerating products (FDP) in late pregnancy. Fifteen mothers with undisturbed foetal growth served as controls. No statistical differences could be found between these two groups of mothers in any of the studied blood parameters. It is thus concluded that a defect in the haemostatic-fibrinolytic balance seems not to play any very important role in the etiology of intrauterine growth retardation.

The use of radiolabelled monoclonal antibodies to human milk fat globule membrane antigens in antibody-guided tumour imaging, and administration of therapeutic dose of labelled antibody in wide-spread ovarian carcinoma. A preliminary report.

Monoclonal antibodies generated against human milk fat globule membrane antigens were used in antibody-guided tumour imaging and palliative therapy in a case of wide-spread ovarian carcinoma. Antibody III H 2, which previously has been shown to react with 100% of ovarian cystadenocarcinomas showed a strong reactivity with tissue sections obtained from the primary and metastatic tumours of the patient. Immunoglobulins were purified from mouse ascitic fluid containing III H 2 and labelled with 123I or 131I with the iodogen method. 80 MBq (2 mCi) of 123I-labelled antibody was given intraperitoneally in 500 ml of PBS and the uptake of radiolabel was followed daily with emission tomography. Radiolabel was mainly located in the peritoneal cavity; only a very low activity was seen in the thyroid gland and urinary bladder. A therapeutic dose consisting of 600 MBq (15 mCi) of 131I-labelled antibody was followed nine days later and the localization of the antibody was followed.

Evaluation of the value of fluorometric serum heat stable alkaline phosphatase assay in patients operated on for ovarian tumors.

The usefulness of a simple fluorometric assay for serum heat-stable alkaline phosphatase (HSAP) in the diagnosis and follow-up of ovarian cancer patients was evaluated. 50 percent of the patients with malignant ovarian tumors had serum HSAP-activities above the upper reference range. Active production of this tumor marker in malignant but not in benign ovarian tumors was demonstrated by analysing serum HSAP-activities in ovarian vein blood. After operation, serum HSAP-activities decreased in all cancer patients with elevated preoperative values. Our results suggest that fluorometric serum HSAP-assay may be a useful alternative method for the determination of this tumor marker especially in a clinical laboratory.

Subtotal hysterectomy in emergency obstetrics.

Emergency obstetric subtotal hysterectomy was performed in 11 women over a 20-year period in the University Central Hospital of Tampere. The incidence of these operations was 1 in 7,623 deliveries. During this period the incidence of uterine rupture was 1 in 13,976 deliveries. The other indications included placenta accreta, atonic postpartum haemorrhage and haemorrhage during caesarean section. There were no maternal deaths or major complications. The authors recommend safe subtotal hysterectomy operation of choice in these emergency cases.

Primary infertility and uterine anomalies.

During a 20-year period, 19 (9.1%) of 208 patients with uterine anomalies had primary infertility. Women with unicornuate uteri had the highest (15%) incidence of primary infertility, which was found in the other groups of uterine anomalies in 7% to 13% of the patients. The cause of infertility was a nonuterine factor in 12 cases: hormonal (8), endometriosis (2), tubal (1), or male (1). The reason for infertility remained unknown or the patient conceived during investigation in five cases. Malformation of the uterus was considered the sole reason for infertility, and metroplasty was performed in two cases. During the follow-up period, 14 patients (74%) achieved pregnancy: 6 spontaneously, 3 after curettage, 2 after metroplasty, 1 after clomiphene treatment, 1 after hysterosalpingogram, and 1 after conservative endometriosis surgery. Four of five cases without pregnancy had a nonuterine factor as the cause of infertility, and in one case it may have been a uterine anomaly--a unicornuate uterus with a rudimentary horn. The results indicate that uterine anomalies are rarely the reason for infertility. Nonuterine causes of infertility must be ruled out before metroplasty is performed, as a last resort.