Modified fetal biophysical profile in the assessment of perinatal outcome.

The aim of the study is the evaluation of variables of the biophysical profile in the assessment of perinatal outcome. The prospective study included 87 pregnant women with singleton pregnancy in the 28th to 42nd week of gestation with clinically and ultrasonically verified fetal growth retardation, where the fetal biophysical profile was assessed antenatally. Through the factor analysis of biophysical profile variables we obtained values indicating the contribution of individual variables to the predictability of perinatal outcome. 70% of the patients were examined in 15 minutes according to the principles of modified biophysical profile. The most sensitive variable of the biophysical profile in the prediction of perinatal outcome was the amniotic fluid volume, followed by fetal breathing movements, non-stress test and fetal movements, while the lowest prediction value was assigned to the fetal tone. The modified biophysical profiles need to be perfected on a larger number of pregnant women, which would advance the predictability of this method in detection of hypoxically endangered fetuses.

[HPV infection of the genital system: new findings]. / HPV-infekcije genitalnog sustava: nove spoznaje.

The expansion of our knowledge in the field of pathology, epidemiology and molecular biology of human papillomaviruses (HPV) has defined them as the major and best understood class of human tumor viruses. The interaction of HPV with genome of host cells produces the majority of cytologic abnormalities responsible for neoplastic transformation and makes early cervical cancer screening possible. This review of the current knowledge of HPV infection biology, diagnosis and therapy facilitates understanding of the clinical significance of these viruses.

Effect of long-term cocaine administration to pregnant ewes on fetal hemodynamics, oxygenation, and growth.

OBJECTIVE: To assess uterine and fetal blood flows by Doppler velocimetry and fetal growth and oxygenation in pregnant ewes treated daily with cocaine and to determine whether cocaine impairs fetal cardiac and cerebral reactivity. METHODS: The study groups received 70 mg (n = 7) or 140 mg (n = 7) of cocaine and the control group (n = 7) received placebo injected intramuscularly daily on days 60-134. Hemodynamic data were measured at rest and during two acute hypoxic tests at cesarean delivery performed on day 134. RESULTS: The fetal heart rate (FHR) and umbilical and uterine resistance indices (RIs) were higher in the cocaine groups than in the control group (FHR: 187 +/- 8 and 166 +/- 8 beats per minute at 83 and 123 days, respectively, in controls and 9-11% higher in cocaine groups; umbilical RI: 0.79 +/- 0.06, 0.60 +/- 0.04, and 0.52 +/- 0.06, at 83, 105, and 123 days, respectively, in controls and 11-17% higher in the cocaine groups [P < .01]; and uterine RI: 0.40 +/- 0.05, 0.40 +/- 0.04, and 0.37 +/- 0.04, at 83, 105, and 123 days, respectively, in controls and 13-35% higher in cocaine groups [P < .05]). At delivery on day 134, the following characteristics were found to be different in the cocaine groups: fetal weight (4.03 +/- 0.2 kg in controls and 15-21% lower in the cocaine groups [P < .02]), partial pressure of oxygen (26.5 +/- 1.4 mmHg in controls and 15-16% lower in cocaine groups [P < .05]), umbilical RI (0.40 +/- 0.03 in controls and 11-17% higher in cocaine groups [P < .01]), cerebral RI (0.61 +/- 0.03 in controls and 9-15% lower in cocaine groups [P < .01]), and cerebral-umbilical ratio (1.52 +/- 0.04 in controls and 22-23% lower in cocaine groups [P < .001]). During the hypoxic tests, the cerebral RI (P < .05) and the cerebral-umbilical ratio (P < .05) decreased significantly less in the two cocaine groups. The FHR response was reduced significantly in the two cocaine groups (P < .05). CONCLUSION: Long-term exposure to cocaine induces uterine and fetal blood flow disorders, fetal growth restriction, and hypoxia. It reduces the capability of the cerebral vessels to vasodilate and the heart rate to increase during acute hypoxia.

Twenty-day cerebral and umbilical Doppler monitoring on a growth retarded and hypoxic fetus.

In one growth retarded and hypoxic fetus, the cerebral and umbilical hemodynamic changes were assessed (by Doppler), daily over 20 days. The fetal brain was investigated by magnetic resonance imaging (MRI) close to the delivery, and because the fetus died at delivery we performed an anatomical study of the fetal brain. The evolution of the fetal hemodynamics (day by day) was interpreted according to the MRI findings and the clinical findings. During the period of observation (under sustained hypoxia) the fetal deterioration was characterized by: (a) the progressive development of the oligohydramnios (190d), (b) the disappearance of the vascular reactivity (eight successive cerebral resistance index (RI) constant at 194d), (c) the occurrence of fetal heart rate decelerations (199d), and finally (d) the increase of the cerebral vascular resistances with reduction of the brain perfusion (204d). The anatomical study of the brain showed a periventricular congestion however the histology revealed hypoxic lesions like gliosis and a marked vasodilation of the anterior and middle cerebral arteries. Finally in addition to single Doppler measurements performed 1 week before delivery (for prediction of fetal outcome), one can suggest to use the 'loss of fluctuation of the cerebral RI' to identify the beginning of the period of very high risk for the fetus. Such hypothesis may have to be confirmed on a larger number of pathological pregnancies.

[Genetic diagnosis and therapy of hereditary breast carcinoma]. / O genetskoj dijagnostici i terapiji hereditarnog karcinoma dojke.

Congenital genetic disturbances in the genes BRCA1 and BRCA2 could lead to the forming of mamacarcinoma and ovarian carcinomas. The probability of illness is by an existing gene defect very high, and mostly young women are already affected. A direct anamnestic identification of high risk person with a following proof of gene mutations could help the patient. The way of the clinical-consultation which is recommending the BRCA1-BRCA2-test in reasons for an early recognition diagnosis is at the moment subject in clinical and scientific research.

[New findings about placental circulation using ultrasound]. / Novije ultrazvucne spoznaje o posteljicnom krvotoku.

Introduction of transvaginal color Doppler has enabled precise analysis of placental circulation in early pregnancy. The purpose of this paper is to summarize the current understanding of the anatomy and physiology of the early placental circulation. Study of uteroplacental circulation has demonstrated a progressive decrease of peripheral resistance from large toward small branches during first and early second trimester of pregnancy. Doppler study of umbilical circulation has also shown a significant fall of resistance from umbilical artery to its branches. Analysis of uteroplacental circulation in abnormal early pregnancy has shown differences in comparison with normal values. Using of transvaginal color Doppler in early pregnancy is not successful in prediction of abnormal late pregnancy. Color Doppler is useful in diagnosis of placental and umbilical cord pathology. The duration of pulsed Doppler examination in early pregnancy should be reduced to minimum if we want to avoid excessive heating of embryonic tissue.

The assessment of normal early pregnancy by transvaginal color Doppler ultrasonography.

Transvaginal color Doppler was performed in 198 volunteer pregnant women whose menstrual age ranged from the fifth to the twelfth week. In all patients an attempt was made to obtain signals from both uterine arteries, peritrophoblastic/retroplacental vessels, umbilical arteries, fetal aorta, intracranial vessels, and corpus luteum flow. With the combination of color and pulsed Doppler transvaginal sonography, detection of vascular structures was greatly facilitated and the amount of time for examination significantly reduced. Flow velocity waveforms were measured and results were analyzed by calculation of the Resistance Index. During the early stage of pregnancy, we were able to locate both uterine arteries in all cases and continuous diastolic shift signal was found. Flow in the peritrophoblastic/retroplacental area was observed with an overall success rate of 94%. Blood flow in the umbilical artery and fetal aorta was visualized by color Doppler starting from the seventh week. Intracranial blood flow could be visualized starting from the tenth week in some cases. Diastolic flow in these vessels was detectable starting from the twelfth week. Corpus luteum flow was found in 148 cases (75%) and the Resistance Index decreased as pregnancy progressed.

Transvaginal color Doppler study of middle cerebral artery blood flow in early normal and abnormal pregnancy.

Transvaginal color and pulsed Doppler sonography was performed on 106 singleton pregnant women; 75 had clinically normal pregnancies, and the remaining 31 patients had complicated pregnancies with vaginal bleeding. The gestational ages ranged from the 7th to 18th menstrual weeks. The aim of the study was to establish the earliest gestational age at which intracranial blood flow could be detected, in particular in the middle cerebral artery. The intracranial circulation becomes visible at the 8th week of gestation (7 weeks and 3 days). The end-diastolic component of blood flow is inconstantly present from the 11th to the 13th gestational week, and is always detected thereafter. A significant decrease in the pulsatility index (p < 0.05) and peripheral flow impedance index (p < 0.001) was observed during the early weeks of pregnancy in both the normal and complicated pregnancies. There was no significant difference between the groups (p > 0.05). Results suggest that Doppler studies of middle cerebral arteries in early pregnancy are unlikely to be of value in identifying fetal hemodynamic disorders in the early stages of spontaneous abortion.

Transvaginal color Doppler assessment of uteroplacental circulation in normal and abnormal early pregnancy.

Transvaginal color Doppler offers the potential to study uteroplacental circulation in early normal pregnancies and pregnancies associated with intrautine fibroids. A total of 62 patients (30 early pregnancies complicated by myoma and 32 normal pregnancies representing the control group) whose gestational age ranged from the 6th to the 14th week were examined. The equipment used was an Aloka color Doppler SSD-680 with 5.0 MHz curve-linear transvaginal transducer. The main uterine, radial and spiral arteries were identified in all patients. Peak systolic velocity and resistance index were measured and automatically calculated. Statistical analysis used was Student t-test. This study documents a physiological decrease in impedance in the uteroplacental circulation in pregnancy associated with fibroids, while the blood velocity of the radial arteries showed a significant increase between the 10th and 14th week of gestation.

Clinical value of the assessment of gynaecological tumour angiogenesis by transvaginal colour Doppler.

Angiogenesis occurs in the body in only a few physiological conditions, but it regularly precedes carcinogenesis. Neovascularisation is a term well known to the pathologist, but with the advent of colour Doppler it is now of interest to those using ultrasonography. Since morphological criteria alone are insufficient to characterise space occupying lesions, visualisation of newly formed vessels and consequently, their blood flow characteristics, seems to provide a clearer distinction in vivo between benign and malignant gynaecological tumours. Very low resistance indices in newly formed vessels, as a predictor of malignancy, have already been established. The most recent area of investigation covering the differences between centrally and peripherally placed vessels offers additional criteria for diagnosing gynecological malignancy.

Tumour cell proliferation is abolished by inhibitors of Na+/H+ and HCO3-/Cl- exchange.

Cell membrane-associated ion transporters, Na+/H+ exchanger and Na(+)-dependent HCO3-/Cl- antiport, were shown to be important in the regulation of acidic intracellular pH in different cell types. This study investigated the role of the ion exchangers and their inhibitors in the serum-induced proliferation of two murine tumour cell lines, P815 and L929. The presence of Na+/H+ exchanger [inhibited by amiloride and 5-(N-ethyl-N-isopropyl)amiloride (EIPA)] and Na(+)-dependent HCO3-/Cl- antiport [inhibited by 4,4'-diisothiocyanostilbene-2,2-disulphonic acid (DIDS)] was shown on the tumour cell line tested. EIPA suppressed tumour cell proliferation more strongly than amiloride, and its effect was further increased after intracellular acidification by nigericin. DIDS slightly inhibited proliferation of L929 cell line and did not influence proliferation of P815 cells. However, in nigericin acidified cells DIDS had a dose dependent antiproliferative effect. Furthermore, DIDS significantly increased antiproliferative effects of amiloride and EIPA, suggesting the activity of Na(+)-dependent HCO3-/Cl- antiport in tumour cell proliferation. These results demonstrate the importance of Na(+)-dependent HCO3-/Cl- exchange in addition to Na+/H+ antiport, in tumour cell proliferation and indicate the possibility that ion exchange inhibitors could act as antitumour reagents.

Transvaginal color Doppler in the assessment of abnormal early pregnancy.

The study groups comprised 61 pregnant women whose gestational age ranged from 7 to 12 weeks from the last menstrual period. All patients apparently had a normal developing pregnancy; there were no clinical symptoms of pathology e.g. bleeding in early pregnancy. Eighty-two patients with a clinically and ultrasonographically normal pregnancy whose gestational age ranged from 7 to 12 weeks, served as a control group. When the anatomical position of investigated area have been obtained clearly, pulsed wave Doppler sample volume was placed on the structures of interest: the both uterine arteries and intervillous space. There is no statistically significant difference between the Resistance Index (RI) in the left or right uterine artery (P greater than 0.01) and among investigated groups of patients (P greater than 0.01). The intervillous blood flow RI in the case of molar pregnancy was 0.38 with SD +/- 0.03; in blighted ovum 0.43 with SD +/- 0.03, and in missed abortion 0.43 with SD +/- 0.02. It should be stressed that in nine (31%) cases of blighted ova and in five (26%) cases of missed abortion, intervillous space flow could not be detected. In the control group, intervillous blood flow was always visualized and the mean RI was 0.45 with SD - 0.04. Statistical analysis showed significantly higher RI in control group in comparison with other groups of patients (P less than 0.01), and significantly lower RI in molar pregnancy in comparison with other groups of patients (P less than 0.01). There was no difference in RI between blighted ova and missed abortions (P greater than 0.01).

Short-term and long-term stimulation of Na+-H+ exchange in cortical brush-border membranes during compensatory growth of the rat kidney.

The effect of unilateral nephrectomy on Na+-H+ exchange in rat renal cortical brush-border membrane vesicles (BBMV) was studied by the method of acridine orange fluorescence quenching. The exchanger activity in BBMV from remnant kidney increased rapidly by 70-75% within first 30 min following uninephrectomy. Only a slight further increase was found in later stages of renal growth, i.e. 30 min to 7 days following uninephrectomy. The changes in antiporter activity were restricted to Vmax, whereas the Km for Na+ was similar in control and compensatory growing kidney. The increase of Na+-H+ exchange at 15 min was not affected by actinomycin D in vivo, whereas the increase at 48 h was completely abolished indicating that protein synthesis could be involved in the late, but not in the initial stimulation of renal Na+-H+ exchange. The late, but not the initial stimulations of Na+-H+ exchange were associated with elevated activities of cortical (Na++K+)-ATPase indicating that changes in antiporter activity precede those in the (Na++K+)-pump. The early stimulation of Na+-H+ exchange in BBMV in one kidney was induced also by the occlusion of blood flow through the contralateral kidney for 15 min, without removing it. Thirty min after the occlusion was removed and the reflow established, the Na+-H+ exchange in BBMV from the intact kidney decreased to the control values. The observed modulations in renal Na+-H+ exchanger may be regulated by phosphorylation-dephosphorylation events.(ABSTRACT TRUNCATED AT 250 WORDS)

Absence of increased electroneutral Na+-H+ exchange in renal cortical brush-border membranes from hyperthyroid rats.

The fluorescence quenching of acridine orange was used to compare Na+-H+ exchange and ion conductances in renal cortical brush-border membrane vesicles (BBMV) isolated from euthyroid and hyperthyroid rats. In BBMV from euthyroid animals, Na+-H+ exchange was entirely electroneutral. In BBMV from hyperthyroid rats, the total rates of Na+-H+ exchange were about 30% higher than in BBMV from euthyroid animals. However, the electroneutral exchange in these membranes was similar to that in BBMV from euthyroid rats; the observed increase in exchange was due to electrically coupled Na+ and H+ movements through conductive pathways in the membranes. Ion conductances in isolated BBMV were tested with outwardly directed K+ gradients in the presence of carbonyl cyanide m-chlorophenylhydrazone (K+ conductance) or valinomycin (H+ conductance). The K+ conductance was negligible and similar in BBMV from both groups of rats. A significant H+ conductance was present in both kinds of membrane preparations and was by 37% higher in BBMV from hyperthyroid animals. Therefore, our experiments failed to demonstrate an increased electroneutral Na+-H+ exchange in BBMV from hyperthyroid rats. Instead, a finding of a significant electrically BBMV from hyperthyroid rats. Instead, a finding of a significant electrically coupled Na+-H+ antiport in the presence of increased H+ conductance in BBMV from hyperthyroid rats indicates that these membranes may also have increased Na+ conductance.