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Laparoscopic management of ectopic pregnancies is becoming more common. Having recently successfully treated one case of heterotopic pregnancy by laparoscopy in our department, the object of the present paper is to review the literature regarding laparoscopically treated cases of heterotopic pregnancy in order to assess benefits, complications and safety of this procedure. A Medline search yielded 10 additional cases with ampullary, interstitional or cornual tubal pregnancy, respectively. All surgical procedures were uncomplicated and all in utero pregnancies progressed normally. Despite a small number of cases, lack of complications in these reports is encouraging feasibility of laparoscopic management of heterotopic pregnancy.

Embryonic, human spinal ganglion explants were plated at 5-12 weeks postconceptional age and cultured for 5-50 days on a semisynthetic substrate in a serum-containing culture medium without addition of antibiotics or preconditioned medium. The growth pattern in vitro was found to be age dependent. Five- to 6-week ganglia showed a characteristic semicircular growth pattern with bidirectional extension of neurites on top of a monolayer of supportive cells. Explanted 9- to 10-week ganglia showed an extensive, multidirectional neurite outgrowth with less pronounced proliferation of nonneuronal cells. Neurite extension, fasciculation, cell migration and morphology were studied immunohistochemically with antibodies to neurofilament (NF), S-100, and the Thy-1 glycoprotein. Both NF and S-100 were expressed at 5 weeks gestational age in ganglionic neurons and in proliferating Schwann cells in contact with axonal processes, respectively. NF was homogeneously distributed in both cell somata and neurites, whereas S-100 immunoreactivity showed an intense nuclear and a weaker cytoplasmic distribution in spindle-shaped, bipolar Schwann cells. This staining pattern was conserved during differentiation in long-term culture. Thy-1 was expressed on ganglionic neurites forming fascicles by the third week in culture. However, Thy-1 was never expressed until the total age of 10 weeks. In addition, Thy-1 was found on fibroblasts from the first week in culture. The distribution of Thy-1 on the cytoplasmic membrane was similar in both cell types, showing a coarsely granulated membrane staining. The temporal as well as the spatial expression of differentiation antigens in tissue sections of early embryonic spinal cord and spinal ganglia were very similar to what was observed in vitro.

The neurochemical differentiation of bulbospinal noradrenergic and serotonergic neurons has been followed in first trimester human fetuses. Analysis of microdissected CNS regions revealed detectable levels of noradrenaline (NA) and serotonin (5-HT) in pons, medulla oblongata and throughout the spinal cord from 5-6 weeks of gestation. In all regions there was a pronounced increase in tissue levels of the monoamines, especially from 8-9 weeks on. 5-HT levels were lower than NA levels except for pons, where the opposite was true. With increasing fetal age, the results seemed less consistent because of considerable interindividual variations. Using immunohistochemical localization of tyrosine hydroxylase (TH), a marker for noradrenergic neurons, immature cell bodies were seen in the brain stem at the earliest stage studied, that is at 4 weeks of gestation. Several TH and 5-HT-immunoreactive (IR) cell groups were found in pons and medulla oblongata at 5 weeks. Significant structural differentiation of TH- and 5-HT-IR cell bodies was seen during the first trimester. Immunoreactive fibers began to appear at 5 weeks in the cervical spinal cord. At 6 weeks both types of fibers could be found in the white matter throughout the entire spinal cord while fibers in gray matter appeared at 9 weeks. The number of TH-IR fibers was considerably larger than the number of 5-HT-IR fibers. This is the first time the biochemical development of human bulbospinal monoaminergic neurons during the first trimester has been described. Continued investigations of the ontogenetic growth and differentiation of these human bulbospinal monoaminergic neurons will gain necessary insight into the genetically determined capacity for plasticity, potentially possible to activate later in life in response to spinal cord injury. Further, intraspinal transplantation of CNS tissue relevant to the severed spinal cord would by necessity entail selection of embryonic cell populations. Using such therapeutic strategies, detailed knowledge of the inherent capacities of the donor tissues will be crucial.

In utero stem cell transplantation represents a new and still experimental therapeutic strategy for diseases related to the hematopoietic system, i.e. hemoglobinopathies, immunodeficiency diseases and metabolic disorders. To date, a total of 21 cases of transplantations using stem cells either of fetal liver or adult bone marrow origin have been reported in the literature. Success has been limited--with the exception of one case of beta-thalassemia--to four cases with immunodeficiency diseases. In this review the broad therapeutic implications as well as potentials and limitations of this technique are summarized. Furthermore, ethical considerations based on the use of fetal cells are pointed out and a prospective view concerning experimental and clinical future perspectives including the possibility for gene therapy is presented.

Only rare cases of extraovarian Brenner tumors have been described. This report concerns one case of extraovarian Brenner tumor detected in close association with an extraovarian benign serous cystadenoma. Coexistence of these two tumors supports the theory of a common origin either from celomic epithelium or remnants of the embryonic mesonephric system.

In utero fetal stem cell transplantation, a today experimental treatment option, represents a new therapeutic strategy with broad implications for diseases related to the hematopoietic system. The object of the present paper is to give a review of the published literature on fetal stem cell therapy with special reference to immunologi-cal and strategical considerations. Furthermore, ethical considerations on account of the use of fetal cells are pointed out and a prospective view concerning experimental and clinical future perspectives is presented.

Fetal stem cell transplantation may rely on material from therapeutic abortions. It is essential that the stem cell transplant does not transmit any microorganisms that may affect the fetus and that genetically abnormal cells are avoided. To evaluate such contamination, human fetal stem cells collected February 1992 - December 1993 were analyzed for bacterial and fungal growth, and the placentas were karyotyped. Four samples of 70 were positive for different pathogens. Serological screening of 43 women during this period resulted in five seroconversions and revealed one carrier of anti-HCV. Karyotyping revealed two abnormal findings out of 72 samples. Thus, the concept of using material from therapeutic abortions is safe.

To analyse the yield of fetal liver tissue in first trimester abortions and to evaluate the number of nucleated cells obtained from each fetal liver during the sixth to twelfth week of gestation.Prospective descriptive study:University Hospital.Women seeking abortion during a 12 month period 1992/1993.Out of 1271 women seeking abortion, 152 were asked whether they were willing to donate fetal tissue for fetal transplantation. Of these women, 105 (69%) accepted the proposal and underwent a modified low suction vacuum curettage. Fetal liver tissue was obtained in 61 (58%) of these procedures. The frequency at which tissue was retrieved was strongly related to gestational age and rose from 29% in week 6 to 79% in the tenth to twelfth week of gestation. The mean number of nucleated cells obtained from each fetal liver demonstrated a concomitant increase with gestational age, rising from 16 to 43 x 10(6) per liver during these weeks of gestation. Of the 61 cases in which fetal liver was obtained, four subjects were shown to be abnormal by laboratory analyses and 11 did not alter the mandatory follow-up appointment. This left 46 cases for use in the program of fetal to fetal transplantations.Most women seeking abortion seem to be in favor of the idea of fetal tissue donation for the treatment of other fetuses. The possibility of obtaining fetal liver tissue and the number of fetal stem cells retrieved are closely correlated to gestational age. A tissue bank appears to facilitate the operation of a fetal to fetal stem cell transplantation program.

The possible interaction of the newly developed triazole antifungal SCH 39304 with low-dose combined oral contraceptives (OCs) was studied in 15 healthy women. Serum levels of ovarian and adrenocortical steroids and sex hormone-binding globulin (SHBG) were analyzed in samples collected during the OC cycles immediately before, during and after the administration of SCH 39304. The drug was given as a single 400-mg oral dose on day 7 in the second cycle. SCH 39304 did not interfere with the ovulatory inhibitory action of low-dose combined OCs as judged from serum progesterone values. Administration of SCH 39304 caused minor decreases in serum SHBG, cortisol and dehydroepiandrosterone sulfate. The mechanism(s) behind these minor changes is not known.

Seventeen women with stress and 20 with motor-urge urinary incontinence were treated ambulatorily with short-term maximal electrical stimulation. The duration of the treatment was 20 min daily for 12 weeks. According to the patients' subjective evaluation, two thirds were improved. A markedly diminished leakage of urine (greater than 50% by use of pad test) was found in 6 out of 17 women with stress, and in 13 out of 20 women with motor-urge urinary incontinence. There were no significant differences observed in urodynamic parameters between the registrations performed before and after the present electrical stimulation therapy.

Serum concentrations of hCG were determined in blood samples taken 18-20 h and immediately before vacuum aspiration in 45 women in gestational weeks 7-9, admitted for legal abortion. In 35 of the women, a laminaria tent was inserted for cervical dilatation immediately after the first blood sampling. Serum hCG values decreased significantly in the women pretreated with laminaria tent, but were unchanged in the untreated women. This finding may indicate that pretreatment with a laminaria tent induces a partial placental detachment.At the Karolinska Institute at Huddinge University Hospital in Huddinge, Sweden, serum levels of human chorionic gonadotropin (hCG) in 35 patients who had been inserted with a laminaria tent 18-20 hours prior to and immediately after vacuum aspiration were compared with those of 10 women who chose not to have laminaria tents inserted prior to vacuum aspiration. Gestational age ranged from 7 to 9 weeks. All the pregnant women were primiparous. The mean serum hCG values did not differ greatly between the cases and controls (84,260 U/1 and 75,878 U/1, respectively). Yet the mean serum hCG levels of women treated with laminaria tents to induce dilation fell considerably more than those in the control group (76,468 U/1 vs. 84,939 U/1; p.01). The concentrations fell in all treated women. Since serum hCG values normally increase during this period, the decrease indicated that laminaria tents induced partial detachment of the placenta. The results also explained the significant bleeding and/or presence of placental tissue in the cervical canal. These results suggest that laminaria tents cause partial placental detachment as well as labor contractions.

Haematocervix is an uncommon complication after conization. This report deals with 1 case that presented with clinical signs of progressive stenosis and was diagnosed by ultrasonography. Based on analysis of the 3 previously reported cases the pathogenesis of this condition is discussed.

Serum concentrations of 17 beta-oestradiol (E2), unconjugated oestrone (E1), total oestrone (tE1), progesterone (P), follicle-stimulating hormone (FSH) and sex-hormone-binding globulin (SHBG) were measured before and after daily intravaginal administration of 250 micrograms micronized E2 and 10 mg micronized P for 14 days to 12 post-menopausal and for 1 day only (during cycle days 5-8) to 11 pre-menopausal women. In the post-menopausal women the levels of all steroids increased to maximum values on day 1, 8-10 h after administration and fell thereafter. In the pre-menopausal women the steroid concentrations rose slowly to a plateau level 10-15 h after administration. Significantly higher absorption of E2 and E1 (area under the curve increments) was noted in the post-menopausal than in the pre-menopausal women. In the post-menopausal women the steroid levels measured on days 7 and 14 corresponded to those observed in the very early or late luteal phase. Area under the curve increments were usually smaller on days 7 and 14 than on day 1 and the absorption kinetics altered to a 'pre-menopausal' pattern. FSH levels were significantly reduced as from 12 h after administration on day 1 and onwards. A slight (10%) but significant increase in SHBG levels was noted on day 14. It was concluded that the combined E2 and P treatment used in this investigation brings about a physiological response with only minimal side effects on the liver as judged from changes in SHBG concentrations.

Ten amniotic fluid samples obtained at elective caesarian section were examined for the presence of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA) and the two specific plasminogen activator inhibitors, PAI-1 and PAI-2. u-PA antigen was demonstrated in all samples (mean concentration equivalent to 0.35 iu/ml), but its bioactivity was very low (mean activity 0.13 iu/ml) when assessed by a bioimmuno-assay (BIA) using chromogenic substrate. None of the samples analysed by ELISA technique had measurable levels of t-PA, neither could any activity of t-PA be demonstrated by a sensitive BIA or fibrin plate technique. Significant amounts of both PAI-1 and PAI-2 antigen were present in all samples, and the mean values were 12.2 and 43.4 ng/ml, respectively. The average inhibitory capacity per ml of amniotic fluid measured by assessing the residual t-PA activity following addition of a known amount of single chain t-PA to the samples was 17.3. Thus, this study demonstrates a fibrinolytic system in amniotic fluid, which is characterised by absence of t-PA activity, low bioactivity of u-PA and excess of the two specific inhibitors, PAI-1 and PAI-2. This inhibitory capacity of amniotic fluid may play a role in preventing premature rupture of membranes.

Free amino acid concentrations were determined in maternal plasma and amniotic fluid (AF) under standardized and unstressed conditions in four groups of women comprising 6 gestational and 13 type I diabetics, 10 women with small-for-gestational-age (SGA) infants, and 18 healthy control women between 36 and 39 weeks of gestation. Plasma values for branched chain amino acids (the sum of leucine, isoleucine and valine) did not differ significantly between the four groups. The corresponding values in AF were significantly higher (P less than 0.05) in the type I diabetic group and significantly lower (P less than 0.05) in the gestational diabetic group as compared to the control group. The mean AF C-peptide concentration was elevated but not significantly so in gestational (0.69 nmol/l) or type I diabetic (0.54 nmol/l) pregnancies and significantly lower (P less than 0.05) in women with SGA infants (0.28 nmol/l) as compared to the control group (0.38 nmol/l). There was a significant correlation between C-peptide in AF and branched chain amino acids in maternal plasma (r = 0.63; P less than 0.05) as well as to maternal blood glucose (r = 0.79; P less than 0.01) in the type I diabetic group, which merely suggests a greater beta cell reactivity to insulin secretagogues in offspring of diabetic mothers. The correlation between AF C-peptide and branched chain amino acids in maternal plasma was significantly inverse in women with SGA infants (r = -0.75; P less than 0.05). Both individual, branched chain, or total amino acid concentration in AF were unrelated to AF C-peptide.

In 2108 pregnant women, external abdominal measurements were correlated to the weight of the newborn child. The product of girth and uterine height was more closely correlated to the infant weight than were any of these maternal variables alone or in other combinations, but the accuracy of this method was almost as low as of simple external palpation. For successive estimations of fetal growth the product of maternal girth and uterine height may be more adequate than either of these variables alone.

Fatty acid composition of lecithin was analysed in midcycle cervical mucus obtained from 19 women using a copper intrauterine device (Cu-IUD) and 16 controls. In both groups, palmitic (16:0) acid was the predominant fatty acid and oleic (18:1) acid the second largest component. In women using a Cu-IUD, levels of myristic (14:0) acid were significantly lower, while levels of linoleic (18:2) and docosahexaenoic (22:6) acid were significantly higher than in controls. These changes in fatty acid composition could not be related to duration of IUD use and were very similar to those observed in women with primary unexplained infertility, suggesting that the Cu-IUD-induced modification of fatty acid pattern in midcycle mucus lecithin may be part of the contraceptive mechanism of action.

Proinsulin, insulin, C-peptide, insulin-binding antibody, and glucose concentrations were measured in amniotic fluid samples from 43 insulin-treated diabetic patients and 17 nondiabetic control patients between the thirty-sixth and thirty-ninth weeks of gestation. Insulin-binding antibodies in amniotic fluid were present in only three diabetic patients, although antibodies in maternal serum were found in 22 of the diabetic subjects. In the diabetic group, maternal serum insulin-binding antibodies were statistically unrelated to levels of C-peptide in amniotic fluid. The mean amniotic fluid concentrations of proinsulin (0.07 nmole/L), insulin (0.08 nmole/L), C-peptide (1.17 nmoles/L), and glucose (2.09 mmoles/L) were markedly elevated (p

Serum concentrations of estradiol-17 beta and its metabolites estrone (unconjugated) and total estrone (mainly estrone sulfate) and of progesterone were measured before and after application of one vaginal suppository containing 250 micrograms estradiol-17 beta and 10 mg progesterone to 10 previously unsubstituted healthy postmenopausal women with normal pretreatment serum steroid levels. Vaginal hormone cytology was performed prior to administration of the estrogen-progesterone combination. An atrophic vaginal mucosa was found in 5 and a moderate proliferation in the other 5 women. A significant association was found between proliferation and pretreatment values of estrone, but not with other steroids. There was a clear, significant association between steroid absorption kinetics and the condition of the vaginal mucosa as indicated by cytological data: significantly higher absorption was found in women with an atrophic vaginal mucosa.

The fatty acid composition in cervical mucus was determined in 37 pregnant and 17 nonpregnant women using gas liquid chromatography. In both groups palmitic acid (16:0) and oleic acid (18:1) were the predominant acids comprising more than half of the total amount. Compared to nonpregnant controls, pregnant women had markedly elevated levels of oleic acid (18:1), while mean levels of myristic acid (14:0) and stearic acid (18:0) were significantly lower. These pregnancy-induced changes in fatty acid pattern could not be ascribed to the increased viscosity of cervical mucus. Only minor differences in fatty acid pattern were found between women in first trimester and at term. In contrast to nonpregnant controls, a significant negative correlation between levels of myristic acid (14:0) and docosahexaenoic acid (22:6) was found in pregnant women, indicating a redistribution of these two fatty acids during pregnancy. The present study demonstrates that pregnancy alters the fatty acid composition of cervical mucus lecithin, and that the characteristic changes are present before the 10th gestational week.

This report concerns one case of tubal pregnancy in which the initial PAD indicated a hydatidiform mole. However, re-examination revealed histologically marked hydropic degeneration. This implication emphasizes the complexity of histopathologi-cal examination of placental tissue.

In a prospective study of 83 women, two different physiotherapy methods for strengthening the pelvic floor muscles after childbirth were evaluated. The training program was carried out by the patients at home for 12 weeks, starting 8 weeks after spontaneous uneventful delivery. Forty-two women did pelvic floor exercises in accordance with the method presented by Kegel (1). Forty-one women used standard vaginal cones with weights increasing in 10 g stages from 20 to 100 g, to be retained in the vagina both when standing erect and moving. Pelvic floor muscle strength, defined as the weight in grams of the heaviest cone that could be retained in the vagina, was recorded before and after the 12-week training period. Training with vaginal cones produced significantly better pelvic floor muscle strength than did exercise without cones.

Amniotic fluid concentration and content (amniotic fluid volume X concentration) of C-peptide and catecholamines (epinephrine, norepinephrine) and their interrelationship was studied in nine women with gestational diabetes, in 14 women with type I diabetes, and in 20 healthy control women between the thirty-sixth and thirty-ninth week of gestation. Mean amniotic fluid volume was significantly larger (p less than 0.05) in the type I diabetic group than in the control group. Mean concentration and content of amniotic fluid C-peptide were elevated in women with gestational diabetes, significantly so in women with type I diabetes (p less than 0.05) as compared with nondiabetic control women. Mean amniotic fluid catecholamine concentrations were lower, although not statistically so, in both insulin-dependent and gestational diabetic women than in control women. Mean amniotic fluid catecholamine content was higher, although not statistically so, in women with gestational diabetes than in control women. In the type I diabetic group, epinephrine content was significantly lower (p less than 0.05) and norepinephrine content significantly higher (p less than 0.05) than in the control group. A significant positive correlation between the content of norepinephrine and C-peptide was found in control women (r = 0.57; p less than 0.05) and in women with gestational diabetes (r = 0.75; p less than 0.05). The close interrelationship could indicate a parallel maturation of these two hormonal systems.

The interrelationship between amniotic fluid (AF) concentration and content (AF X conc) of C-peptide and cortisol was studied in four groups of women comprising 10 gestational and 16 type-I diabetics, 11 women with intrauterine growth retarded fetuses (IUGR), and 17 healthy control women. Mean AF volume was significantly greater (P less than 0.05) in the type-I diabetic group than in the control group. Both concentration and content of AF C-peptide was significantly higher in the type-I diabetic group than in the control group (P less than 0.05 and P less than 0.01, respectively). The corresponding values were significantly lower in mothers with IUGR fetuses compared to controls (P less than 0.05). AF cortisol content was significantly higher (P less than 0.05) in the gestational diabetic group compared to the control group; there were no other significant differences between the groups regarding the cortisol concentration or content. Both cortisol and C-peptide contents were significantly interrelated in both control women (r = 0.68, P less than 0.01) and women with gestational (r = 0.68, P less than 0.05) and type-I diabetes (r = 0.63, P less than 0.01). The C-peptide/cortisol ratio was lowest in the IUGR group and highest in the type-I diabetic group. The same ratio was intermediate and almost equal in the control and gestational diabetic group. Both C-peptide and cortisol concentrations were unrelated to AF volume as well as infant birthweight. C-peptide content was significantly correlated to birthweight percentile in type-I diabetic women (r = 0.61, P less than 0.05). No such correlation was found in the three other groups.

Fibrinolytic activity (FA) was assessed by the fibrin plate technique in 47 amniotic fluid samples obtained at 35 to 39 weeks' gestation. In amniotic fluid the FA (63.1 +/- 2.5 mm2) was considerably elevated when compared with previously reported serum levels of pregnant women. After centrifugation of the amniotic fluid samples a highly significant reduction of FA in the supernatant was recorded (42.9 +/- 1.3 mm2), suggesting that the cells of fetal origin are the main source of the high plasminogen activator activity demonstrated in amniotic fluid. A significant rise in amniotic fluid FA was demonstrated beyond the 37th gestational week. Furthermore, significantly greater FA was recorded in amniotic fluid samples from women with spontaneous onset of labor within a week. However, a single FA determination in amniotic fluid obtained by routine amniocentesis was found to be of little value for prediction of the time interval to delivery.

During the last 7-year period, the second twin was delivered by cesarean section in three of 161 twin pregnancies in our Department. The main reasons for this procedure were fetal distress caused by malpresentation or cord prolapse in 2 cases and in the third case placental separation. Cesarean section for delivery of the second twin is justified only in selected cases.

The aim of the present study was to characterize the morphological and neurochemical differentiation of mesencephalic dopaminergic neurons in human embryos, derived from elective first trimester abortions. Embryonic brain tissue was taken for analysis of tyrosine hydroxylase (TH) by immunohistochemistry and Western blot, and for analysis of endogenous dopamine (A) content using HPLC-ED. TH expression was first detected at 3.5 weeks of gestational age (Carnegie stage 11) by immunohistochemical staining of the primordial sympathetic trunk along both sides of the neural tube. In sagittal sections of the intact 4.5-week-old embryo, a small, distinct population of rounded, densely packed TH-immunoreactive perikarya with short primary processes was seen in the midbrain. During the latter half of the first trimester, the number of TH-stained cells as well as the length and number of axonal processes projecting toward and into the developing neostriatum increased rapidly. At the end of the first trimester, varicose fibers could be detected in the striatal anlage. In order to verify that TH was the antigen recognized by the antibodies used for immunohistochemistry on human tissue specimens, mesencephalic tissue of 5-10 weeks gestation was analyzed by Western blot technique. A single, homogeneous band with the apparent molecular weight of approximately 60 kDa was clearly detected at 5 weeks of age. The amount of TH/mg total protein increased at least 10-fold between 5-10 weeks of gestation. For comparison, the mesencephalon and the forebrain/basal ganglia were analyzed for endogenous DA content using HPLC-ED. DA was first detected at 5.5 weeks of gestational age in both mid- and forebrain, and DA levels were found to increase exponentially from 7 to 7.5 weeks of age, reaching 4-5.5 ng DA/mesencephalon and 50-75 ng DA/g caudate nucleus-putamen anlage at the end of the first trimester. Together, morphological and biochemical data presented here constitute evidence for a very early appearance, migration, and differentiation as well as functional development of human mesencephalic dopaminergic neurons and their projections into target areas during the first trimester.