Effect of eicosapentaenoic acid and docosahexaenoic acid supplementation on C-peptide preservation in pregnant women with type-1 diabetes: randomized placebo controlled clinical trial.

BACKGROUND/OBJECTIVES: Type-1 diabetes mellitus (T1DM) is caused by autoimmune insulitis. There are evidences that pregnancy and n-3 fatty acids exhibit suppressive effect on human inflammatory system. SUBJECTS/METHODS: Ninety pregnant women with T1DM were included in the prospective randomized placebo controlled clinical trial. Forty-seven of them were put on standard diabetic diet enriched with EPA and DHA twice a day (EPA 120 mg and DHA 616 mg; Study group) and 43 pregnant diabetic women were on standard diabetic diet with placebo (Control group). Duration of T1DM in all participants was between 5 to 30 years. Blood samples were analyzed from all pregnant women for fasting C-peptide (FC-peptide), fasting plasma glucose (FPG) and HbA1c in each trimester throughout pregnancy and after delivery. Umbilical vein blood was analyzed for fetal C-peptide level, glucose concentration and insulin resistance. RESULTS: In the Study group FC-peptide concentration raised from 59.6±103.9 pmol/l in first trimester, to 67.7±101.3 pmol/l in the second trimester and to 95.1±152.7 pmol/l in the third trimester. Comparing the FC-peptide values during first and third trimester a statistically significant increase in third trimester was found (P<0.001). In the Control group FC-peptide concentration ranged from 41.7±91.6 pmol/l in the first trimester to 41.2±70.9 mmol/l in the second trimester while in the third trimester it reached 52.4±95.3 pmol/l. Comparing the FC-peptide values during first and third trimester the statistical difference was not significant. CONCLUSION: Combining of LC n-3 PUFAs and pregnancy yields immunological tolerance and stimulates the production of endogenous insulin in women with T1DM.

Histoenzymatic and immunocytochemical characteristics of extravillous trophoblast cells of placental basal plate as parameter of their function in hypertensive pregnancy.

An intense activity of enzymes which actively participate in the renin-angiotensin-aldosterone system was shown in extravillous trophoblast cells which are involved in the performing of spiral arteries into uteroplacental vessels. The hydrolase activity in villous trophoblast underwent important variations, but it was constant in cells of the extravillous trophoblast. Activity of lysosomal hydrolases, of leucine aminopeptidase and N-acetyl glucosaminidase type, was markedly positive in X-cells, while negative in the villous trophoblast. Beta glucuronidase activity has shown moderate activity in cells of extravillous trophoblast, while in villous trophoblast it was weakly emphasized or negative. Intense activity of prostaglandin E2 dehydrogenase in the way of strongly emphasized microsomal reaction was noted exclusively in extravillous cells of basal plate, especially in perivascular cell groupings. Within all examined enzymes activities, only the membranous activity of alkaline phosphatase was of the same intensity in cells of extravillous trophoblast. Lacking of penetration of these cells into the spiral arteries wall in EPH-gestosis, which also means loss of their close contact with the blood of a pregnant, implicates the practical meaning of these observations.

Hemostatic problems before, during and after delivery.

Normal pregnancy and childbirth are known to be associated with marked changes in the coagulation and fibrinolytic systems. Generally, enhancement of clotting activity persists to prevent the risk of major hemorrhage. Hemostatic problems, either associated with a specific complication of pregnancy and labor or due to a hereditary or acquired bleeding diathesis or thrombophilias, present a significant cause of maternal and neonatal morbidity and mortality. This article reviews hemostatic disorders in pregnancy and the peripartal period from the standpoint of the obstetrician.

Review on prostaglandin and oxytocin activity in preterm labor.

The principal difference between term and preterm labor is how they are activated. It has been proposed that term labor results from physiological activation of the common terminal pathway, whereas preterm labor is a pathological condition caused by multiple etiologies that activate one or more of the components of this pathway. Increased uterine contractility at preterm labor results from activation and stimulation of the myometrium. Myometrium is stimulated by increased concentrations ofprostaglandins and oxytocin. Increased production of stimulatory prostaglandins by intrauterine tissues is generally considered a central component of the cascade of events leading to preterm parturition. Prostaglandins act to mediate cervical ripening and to stimulate uterine contractions and indirectly to increase fundally dominant myometrial contractility by up regulation of gap junctions, oxytocin and arginine vasopressin receptors and synchronizations of contractions. The authors tried to explain the role and influence of oxytocin in human parturition, as well as the novel therapy in inhibiting the contractions in preterm labor. The selective oxytocin inhibitor was tested in vitro on human myometrium and decidua by the author of this article among the first in the world.

Giant uterine leiomyoma devascularized by embolization prior to surgical removal.

A 49-year-old woman presented a tumor of pelvic origin filling almost the whole abdominal cavity. Angiography confirmed that it arose from the uterus. Bilateral internal iliac artery embolization was performed prior to surgical removal. It was found to be a 25kg uterine leiomyoma.

Antiphospholipid antibody syndrome and fetal outcome.

The presence of antiphospholipid antibodies, lupus anticoagulant and anticardiolipin antibody in patients with systemic lupus erythematosus has been associated with the clinical features of thrombosis, fetal loss and thrombocytopenia, and the syndrome is designated as antiphospholipid antibody syndrome (APS). APS has been increasingly diagnosed in patients without underlying autoimmune disease and is most frequently seen in obstetric patients suffering spontaneous abortion, preeclampsia and intrauterine growth restriction. The hypothesis underlying most research into the pathophysiology of APS is that autoantibodies are not only the markers of the disease, but also directly contribute to the development of clinical features. This review summarizes recent information on the pathophysiology and potential roles of autoantibodies in the obstetric patients suffering, particularly in the subgroup of repeated spontaneous abortions.

Influence of hyperglycemia on early embryonal growth in IDDM pregnant women.

The association between maternal diabetes mellitus and congenital anomalies is well established. Congenital malformations in the offspring of diabetic mothers account for approximately forty percent of perinatal deaths. The aim of the study was to identify incidence of early embryonal delay in diabetic and normal pregnancies, and to examine relationship between the HbA1c values and early embryonal growth delay. One hundred twenty IDDM and fifty and four healthy women enrolled into the study. Pregnancy duration was confirmed by beta-HCG measurements within a fortnight from the missed menstrual period. No statistical difference was detected between the studied groups for gestational age, prepregnancy weight, newborns' birthweight and sex. The risk of spontaneous abortion in IDDM pregnancy with delayed embryonal growth was eight times higher than in IDDM pregnancies with normal growth pattern. No fetal malformations were determined in fetuses or newborns of either groups. The mean value and standard deviation of HbA1c in the IDDM patients with normal embryonic growth was 7.3 +/- 1.5%, and in the group of early embryonic growth, delay 9.39 +/- 2.37% respectively (F = 7.79; p = 0.006). This study confirmed the relationship between embryonal growth, spontaneous abortions and abnormal metabolic control of IDDM pregnancies.

Clinical and scientific results in perinatal care of pregnancy complicated by insulin dependent diabetes mellitus in Croatia.

At the Department of Obstetrics and Gynecology, Perinatal Unit for Diabetes and Fetal Growth, School of Medicine, Zagreb, perinatal care of pregnancies complicated with insulin dependent diabetes melitus (IDDM), has been performed for more than 36 years. The intention of this review is to show our own results in the management of IDDM pregnancies and the latest clinical advances in perinatal care of such pregnancies. Pregnancy complicated with IDDM is at risk because of numerous maternal, fetal and neonatal complications. Recent advances in medicine, especially in diabetology and perinatology, helps clinician avoid or lessen antenatal or perinatal complications in IDDM pregnancies. The main result of improved perinatal care is that today fetal and neonatal mortality in IDDM pregnancy is almost equal to that of healthy pregnant population. Intensive preconceptual care and optimal regulation of IDDM have resulted not only in decreased perinatal mortality but also in a decreased rate of congenital malformation. Tight glycemia control during pregnancy has a beneficial effect on fetal growth. Intensive control of fetal growth, verification of lung maturation at term by amniocenthesis, and control of fetal oxygenation will result in delivery of a mature eutrophic newborn with the lowest rate of neonatal complications possible. Perinatal mortality of less than 2% in IDDM pregnancy can be obtained by planned delivery between 38 and 39 weeks of gestation by either vaginal route or cesarean section, depending on indications. After delivery, intensive care of the newborn is necessary.

Effects of preeclampsia and eclampsia on cord blood coagulation tests.

Blood coagulation tests were determined in fifty-three paired umbilical cord blood and maternal venous blood samples originating from term singleton vaginal cephalic deliveries. The index group comprised seventeen deliveries complicated by preeclampsia or eclampsia, and the control group comprised thirty-six healthy women with uneventful pregnancies and deliveries. Mean values obtained from the coagulation and fibrinolytic assays did not significantly differ between study groups, except for antithrombin III levels in index group of neonates, which were significantly lower. Comparison of coagulation and fibrinolytic characteristics between mothers and their neonates produced expected level of difference due to immaturity of their haemostatic mechanisms. We found alterations in maternal blood coagulation and fibrinolysis and evidence of increased intravascular coagulation with severe preeclampsia and IUGR.

Ponderal index and disproportionate fetal growth in IDDM pregnancies.

Disproportionate macrosomia refers to excessive weight characterized by a high weight/length ratio. Disproportionate macrosomia is associated with an increased likelihood of neonatal complications. The aim of the study was to investigate incidence of ponderal indexes and disproportionate fetal growth rate in newborns originating from IDDM and healthy pregnancies. 144 IDDM pregnancies and 432 uneventful pregnancies with normal findings of oral glucose tolerance test were studied, and matched 1:3 for gestational age, sex of newborn, mothers's parity and year of delivery. The pregnancies selected terminated between 30-40th gestational week and resulted with live birth. Mean birth weight (+/- SD) in IDDM group was 3558 +/- 817.6 compared to 3132.4 +/- 534.4 grams of control group (F = 51.49; p < 0.001), mean birth length was 49.8 +/- 3.5 vrs 49.1 +/- 2.5 (F = 8.55; p < 0.005), mean gestation age by examination for both study groups 37.9 +/- 1.9, mean ponderal index of IDDM group was 2.82 +/- 0.28 vrs. 2.63 +/- 0.24 (F = 64.52; p < 0.001) of control group, rate of Apgar score < 7 was 21.14% vrs. 5.08% (chi 2 = 30.30; p < 0.001). 53.4% of IDDMs had macrosomia compared with 8.33% of control infants (chi 2 = 140.25; p < 0.001), and 35.24% of IDDMs had disproportionate macrosomia compared with 5.79% of control infants. Significantly higher rate of both proportionally and disproportionally grown infants with macrosomia was found among IDDMs than among control infants. The rate of disproportionate macrosomic infants significantly differ among study group.

Assessment of the nutritional status in Croatian pregnant women by measuring skinfolds.

In a transversal study, we assessed the changes of body composition, body weight gain, skinfold thickness and the distribution of body fat during pregnancy in 181 healthy pregnant women in Zagreb. Weight gain in pregnant women was 14.4 kg on average, out of which 5.7 kg was the total increase in body fat. In healthy pregnant women the weight gain of more than 12 kg causes excessive accumulation of body fat and has no effect on the weight of placenta and newborn. There is no significant correlation between the body weight gain of pregnant women and the weight of newborns. The increase in skinfold thickness is neither proportional nor simultaneous. Changes in biceps and triceps skinfolds indicate the dependency on the level of estrogen, and subscapular and suprailiac skinfolds on the level of progesterone in the blood of pregnant women. The index of centripetal fat pattern decreases significantly in pregnancy and is referred to peripheral redistribution of body fat in regular pregnancy. The expected weight of the newborn (eBW) may be determined by the body mass index (BMI) and triceps skinfold thickness.

The effect of coagulation parameters on the placental respiratory and nutritive function in women having chronic hypertension with superimposed preeclampsia.

The aim of this study was to explore the relationship between coagulation and fibrinolytic system parameters with nutritive and respiratory placental function. We have analysed 79 pregnant women, of which 39 with severe preeclampsia (index group) and 41 healthy pregnant women. When comparing the study groups in third trimester, significantly lower platelet counts, fibrinogen values and antithrombin III values have been found in the index group compared to the control group. Factor VII levels were not found to be significantly different. The control group revealed significantly higher levels of coagulation factors II, V and VIII, compared to the index group. The increase of FDP, reduction of fibrinogen and increase of fibrinolysis in index group, when compared to the control group of healthy pregnant women, are the reflection of the intravascular fibrin deposition that leads to the described coagulation changes and consecutively to the foetal growth retardation. Indirect evidence are the correlation between newborns' weight and fibrinogen levels/fibrinolytic activity.

Holistic approach to analysis of medical data: cancer of the corpus uteri.

Besides the information regarding his/her disease, each hospitalized cancer patient also provides the variety of data regarding his/her psychological, cultural, social, economical, genetic, constitutional and medical background. The aim of this study was to introduce a holistic approach to analysis of medical data, in this case clinical data regarding cancer of the corpus uteri. Such approach requires the collection of data regarding different aspects of the cancer patient, and after the satisfactory sample size is obtained (which should be at least five times greater than the number of examined patient characteristics), the performance of factor analysis. In this study, the authors have processed the data regarding 25 characteristics of 928 corpus uteri cancer patients treated between 1980 and 1990 at the Department for Gynecological Oncology of the University Hospital for Gynecology and Obstetrics, Zagreb, Croatia. In factor analysis, the principal components were rotated after the initial extraction (the authors recommended the use of oblimin rotation) in order to obtain better ground for interpretation of the obtained results. The next step in this approach was the stepwise exclusion of characteristics with smallest communalities according to Kaiser-Meyer-Olkin criteria, and retaining the characteristics and components with the most significant impact on the explained system variance. When the number of principal components and initial analyzed characteristics was reduced to 3-4 and 7-10, respectively, the ultimate interpretations and conclusions were made. This approach outlined some clusters of correlations between medical data which are difficult to identify using other statistical procedures, primarily the impacts of various socioeconomic and hereditary-constitutional variables on overall survival.

Factor analysis of medical data of patients with primary and metastatic vaginal cancer.

This study adds up to the series of studies on application of factorial designs to analysis of cancer patients medical data. Namely, besides the information regarding his/her disease, each hospitalized cancer patient also provides the variety of data regarding his/her psychological, cultural, social, economical, genetic, constitutional and medical background. The aim of this particular study was to analyze clinical data in patients with primary and metastatic vaginal cancer and to compare them with the results of factor analytic approach in some other gynecological cancers, namely vulvar and cervical cancer. In this particular study the authors have processed the data regarding 25 characteristics of 200 consecutive patients with primary vaginal cancer and 300 consecutive patients with metastatic vaginal cancer treated between 1980 and 1994 at the Department for Gynecological Oncology of the University Hospital for Gynecology and Obstetrics, Zagreb, Croatia. The results revealed numerous repeating clusters of variable correlations across all four factor analyses in patients with cervical, vulvar, primary and metastatic vaginal cancers.

Glycosylated hemoglobin and fetal growth in normal, gestational and insulin dependent diabetes mellitus pregnancies.

Aims of the study were: evaluation of HbA1c levels in the peripheral blood of pregnant women with insulin dependent diabetes, gestational diabetes, glucose intolerance, and healthy pregnant controls; implications of HbA1c concentration on detection and the control of women with impaired carbohydrate metabolism in pregnancy; comparison of HbA1c levels with appearance of miscarriages, and premature deliveries; comparison of weight gain during pregnancy to HbA1c levels; comparison of difference from ideal body weight with HbA1c in diabetic pregnant women; comparison of neonatal birth weight and HbA1c levels. 290 pregnant women were enrolled to the study. The highest value of HbA1c was in the group IDDM pregnant women (7.7% +/- 1.8%), and the lowest value of HbA1c was in the control group (4.1% +/- 0.5%). Statistically significant coefficients were found between HbA1c and weight gain during pregnancy, between weight deviation from ideal body weight and HbA1c (r = 0.54 and r = 0.48 respectively); and between newborns weight and HbA1c (r = 0.51). Well regulated glycemia and intensive pregnancy follow-up of diabetic women reduces stillbirths, neonatal complications and neonatal macrosomia incidence.

Amniotic fluid and maternal plasma prostaglandins in hypertonic saline-induced abortion.

Intraamniotic instillation of 20% sodium chloride solution was carried out in 12 women within the 16th to 18th weeks of pregnancy. PgE2 and PgF2 alpha levels were monitored both in amniotic fluid 5 and 11 h following NaCl instillation as well as in the maternal plasma within the 5-h interval up to 36 h after instillation had been performed. A significant increase was observed of both PGE2 and PGF2 alpha concentrations in the amniotic fluid of all women who underwent induction of abortion. PgF2 alpha in amniotic fluid was increasing abruptly during the time of abortion, reaching the value of 249.7 +/- 19.6 ng/l (n = 12; P less than 0.001). Maternal plasma PgF2 alpha showed a continuous mild increase from 20.4 +/- 5.5 ng/l before to the maximum level, recorded 36 h after instillation, ranging within 205 +/- 1.0 ng/l (n = 4; P less than 0.001). A statistically significant increase in the levels of PgE2 and PgF2 alpha in both amniotic fluid and maternal plasma suggests that the release of primary PGs is a pathognomonic event for initiating labor pains, maturation of the cervix in abortions induced via intra-amniotic instillation of hypertonic NaCl solution.

The effect of fetal hypoxia and acidosis on the changes in fetal electroencephalogram during labor.

As artefact-free recordings of the fetal brain bioelectric potentials can only be obtained by specially designed electrodes, an electrode for taking electroencephalogram (EEG) and cardiotocogram (CTG), according to the principle of vacuum electrode developed by Rosen and Scibetta, has been designed. The polygraphic technique was used to examine a total of 65 deliveries, divided into two groups. The first group (n = 33) consisted of newborns free of any signs of hypoxia and acidosis, whereas the second group (n = 32) was comprised of newborns with evident clinical and biochemical signs of hypoxia and acidosis. Fetal hypoxia and acidosis were observed to entail some characteristic changes in EEG, that is, a decrease in the frequency and wave amplitude through the appearance of the isoelectric line (ISO) featuring in severe cases of fetal hypoxia and acidosis. The following changes were found to occur during the development of hypoxia and acidosis:hypoxia, a decrease in the EEG frequency and amplitude, preacidosis with the appearance of both early and late decelerations coupled with a significant drop in the oscillation and, eventually, severe variable decelerations accompanied by terminal bradycardia. The time interval between the manifestation of initial signs of a decreasing central nervous system (CNS) activity and changes in the fetal heart rate was found to be about 10 minutes.

[Incidence of herpes virus (HSV-2) alterations in squamous cells of vagina epithelium (author's transl)]. / Häufigkeit der Herpesvirus (HSV-2)-Veränderungen an den Zellen des Plattenepithels der Scheide.

The authors have analysed 17,519 cytological cervix smears. Alterations characteristic of HSV infection were recorded from squamous cells of vaginal and cervical epithelia in 21 cases (0.12 per cent). Incidences of cytologically detected HSV infection of the vagina and cervix were 0.17 per cent among female factory workers and 0.08 per cent among peasant women. No statistically unambiguous difference was found to exist between the incidences of genital HSV infections in the two groups examined (p greater than 0.05). The majority of women with genital HSV infections was between 21 and 25 years old.