Evaluation of fetal condition in pregnancy complicated by hypertension--biochemical assessment of amniotic fluid. III. Acid-base balance]

Sixty two samples of amniotic fluid, collected by ultrasound guided amniocentesis, were submitted to biochemical investigation including 31 samples from women with pregnancy complicated by hypertension (studied group) and 31 samples deriving from healthy pregnant women (control group with). The following parameters of acid-base balance were measured in amniotic fluids of both groups: pH, pCO2, base deficiency, standard HCO3 and total CO2. Corning device type 168 was used. Distinct metabolic-respiratory acidosis was present in amniotic fluids of studied group showing the decrease of a pH, pO2, standard HCO3 values and an increase of CO2 values and base deficiency. Authors believe in pregnancy complicated by hypertension biochemical environment of intrauterine fetal development with regard to acid-base balance is highly unfavourable.     

Fibrinolytic components in fetal membranes and amniotic fluid

OBJECTIVE: We evaluated fibrinolytic components in plasma and amniotic fluid of pregnant women and in postpartum fetal membranes. STUDY DESIGN: Fibrinolytic parameters in amniotic fluid and plasma were measured by means of enzyme-linked immunosorbent assays. Fetal membranes collected after spontaneous labor at term were analyzed by immunohistochemical methods with immunospecific antibodies against fibrinolytic components. RESULTS: Amniotic fluid contained high plasminogen activator inhibitor-1 concentrations but had low activity. Strong staining for plasminogen activator inhibitor-1 and vitronectin was observed in chorionic trophoblasts and moderate staining in decidual connective tissue. Strong staining for plasminogen activator inhibitor-2 was seen in decidual cells. Although prominent staining of plasminogen activators and plasminogen were observed in the amniotic epithelium, virtually no plasminogen activator inhibitor-1, plasminogen activator inhibitor-2, or alpha 2-plasmin inhibitor staining was detected. CONCLUSION: The delicate balance of fibrinolytic activators and inhibitors in fetal membranes and amniotic fluid may contribute to the triggering of membrane rupture at term.     

Cocaine and metabolites in amniotic fluid may prolong fetal drug exposure

OBJECTIVE: Cocaine and metabolites can be found in the amniotic fluid after maternal use, presumably as a result of fetal urination. The fetus may be repeatedly exposed to the effects of these drugs through contact with amniotic fluid that contains these substances. The purpose of this study was to determine whether the naive fetal lamb generates detectable fetal blood levels of cocaine and metabolites when cocaine is placed directly into the amniotic fluid and, if so, whether fetal swallowing accounts for these findings. STUDY DESIGN: Six pregnant ewes with singleton fetuses of 120 to 125 days' gestation were chronically catheterized for daily sampling of cocaine and metabolite levels in maternal venous plasma, fetal venous plasma, and amniotic fluid over a 7-day period. Esophageal ligation was performed in three additional animals similarly instrumented to evaluate the role of fetal swallowing in the distribution of amniotic fluid cocaine and its metabolites. In each case, at the time of surgery, an Alzet osmotic pump delivering cocaine at 0.5 mg/kg estimated fetal weight per hour into the amniotic fluid was secured to the fetal back. Cocaine and metabolites (benzoylecgonine, ecgonine methyl ester, and norcocaine) were measured daily in material and fetal plasma, amniotic fluid, and meconium by solid-phase extraction and derivatization and quantified by high-performance gas chromatographic techniques. RESULTS: The concentrations of ecgonine methyl ester were highest in the amniotic fluid followed by cocaine and benzoylecgonine. In the normal and esophagus-ligated groups, cocaine, benzoylecgonine, and norcocaine were found in fetal plasma in concentrations of approximately 3% that of amniotic fluid. Ecgonine methyl ester was not detected in fetal plasma from either group. Meconium samples from sheep with and without esophageal ligation demonstrated high levels of norcocaine. CONCLUSION: We conclude that cocaine and metabolites in amniotic fluid enter the fetal circulation to produce detectable plasma levels through routes other than swallowing. Moreover, the results of meconium analyses in the two groups of fetuses suggest that fetal swallowing is not the primary mechanism by which cocaine and metabolites enter the intestine.     

Prenatal corticotherapy and acceleration of fetal maturation. I. Experimental and pharmacological data

Numerous subsequent controlled trials and recent meta-analysis have confirmed the efficiency of antenatal glucocorticoid therapy in reducing both the incidence of respiratory distress syndrome (RDS) and perinatal mortality. Moreover, antenatal glucocorticoid administration reduces the odds of several severe complications relating to immaturity: intraventricular hemorrhage (IVH), ductus arteriosus patency, necrotising enterocolitis, and hemodynamic failure. Exogenous surfactant therapy has not ruled out the benefits of corticosteroids: on the contrary, a synergic effect is obtained when both antenatal and postnatal therapeutic approaches are combined. Very premature infants may also take advantage of the hormonal treatment: in this population, RDS occurrence, IVH incidence and perinatal mortality are also reduced. Unfortunately, despite convincing evidence, the incidence of antenatal steroids therapy has not yet achieved the optimal and desirable level. Obstetricians and pediatricians must be encouraged to ensure high maternal exposure to steroids when preterm delivery is likely to occur.     

In vivo transfer of gene and oligodeoxynucleotides into skin of fetal rats by incubation in amniotic fluid

One of the tools to test an in vitro hypothesis in vivo is transgenic/gene targeting technology. Transgenic technology provides many advantages such as: (1) the study of specific gene function as systemic and developmental effects; and (2) testing of specific gene function chronically. nevertheless, one disadvantage of this technology is the difficulty in tissue-specific targeting of the transgenic expression. Another useful tool is the in vivo gene transfer approach. Therefore, we tested a potential novel model for the study of transgene expression and knock-out using antisense technology. Here, we have demonstrated that incubation of hemagglutinating virus of Japan (HVJ)-liposome complex containing FITC-labeled oligonucleotides in the amniotic fluid of fetal rats resulted in the nuclear localization of fluorescence in the skin (epidermis and dermis). Similarly, transfection of beta-galactosidase gene resulted in positive staining in several surface layers of the skin. Thus, local gene or antisense oligonucleotide transfer approach into the skin may be useful for studying the role of autocrine/paracrine mediators and treating diseases.     

Relaxin levels in amniotic fluid, extraembryonic coelomic fluid and maternal serum in early human pregnancy

Separately identified samples of amniotic fluid and extraembryonic coelomic fluid together with maternal serum were collected from 22 women between 8 and 11 weeks of pregnancy and analysed for relaxin by immunoassay. Relaxin levels in maternal serum (median 1085 pg/ml; range 390-1259 pg/ml) were substantially higher than those in extraembryonic coelomic fluid (median 57.5 pg/ml; range 17-145 pg/ml; P < 0.0001; Mann-Whitney U-test). In turn, the levels of relaxin in coelomic fluid were higher than those in amniotic fluid (median 10 pg/ml; range 10-37 pg/ml; P < 0.0001; Mann-Whitney U-test). A linear correlation was found between relaxin levels in maternal serum and coelomic fluid (r = 0.68; P = 0.001) but there was no relation between levels in the other fluid compartments.     

Fetal and maternal lipoprotein metabolism in human pregnancy complicated by type I diabetes mellitus

Serum lipid, apolipoprotein concentration, and lipoprotein composition were determined in maternal and umbilical venous cord blood at delivery by elective Cesarean section (CS) in 10 singleton, full-term pregnancies with maternal insulin-dependent diabetes mellitus (type I DM), which predated pregnancy, and in 22 nondiabetic pregnancies. The objectives of the study were to determine the influence of maternal type I DM, and hence potential fetal overnutrition on fetal lipid metabolism. There were no significant differences in gestational age, fetal weight, or fetal serum insulin concentration between the type I DM group and those with nondiabetic pregnancies, although fetal venous cord blood glucose was 3.4 mmol/L (3.0-4.5 mmol/L) (median and 25th-75th percentiles) and 2.9 mmol/L (2.0-3.4 mmol/L), respectively, and maternal Hemoglobin A1c [9.6% (8.2-10.7%) and 6.8% (6.3-7.8%), respectively], was significantly greater in the type I DM subjects (P < 0.02 and 0.002 respectively). Plasma nonesterified fatty acid (NEFA) concentrations were lower in the type I DM mothers [0.85 mmol/L (0.56-2.31 mmol/L) compared with 1.14 mmol/L (0.88-1.24 mmol/L] in nondiabetic pregnancies; P < 0.0001). Serum high-density lipoprotein phospholipids (HDL-PL) were increased in type I DM mothers because of elevated HDL2 phospholipid [0.39 mmol/L (0.27-0.48 mmol/L) compared with 0.12 mmol/L (0.06-0.21 mmol/L), respectively, P < 0.01). The maternal HDL cholesterol (C) concentration was not significantly different in the uncomplicated and type I DM pregnancies. However, in the umbilical venous cord blood, serum levels of NEFA [0.49 mmol/L (0.33-1.29 mmol/L) in type I DM compared with 0.13 mmol/L (0.06-0.33 mmol/L) in nondiabetics; P < 0.02)], total cholesterol (TC) [2.87 mmol/L (1.65-4.86 mmol/L) in type I DM compared with 1.65 mmol/L (1.46-1.87 mmol/L) in nondiabetics; P < 0.02]; free cholesterol (FC) [0.97 mmol/L (0.60-1.26 mmol/L) in type I DM compared with 0.62 mmol/L (0.37-0.75 mmol/L) in nondiabetics; P < 0.05), and cholesteryl ester (CE) [1.90 mmol/L (1.44-3.33 mmol/L) in type I DM compared with 1.01 mmol/L (0.83-1.24 mmol/L) in nondiabetics; P < 0.02), triglyceride (TG) (1.06 [0.50-1.91) mmol/L in type I DM compared with 0.29 [0.25-0.36] mmol/l in nondiabetics; P < 0.001), phospholipid (PL) (2.52 [1.73-3.03) mmol/L in type I DM compared with 1.34 [1.27-1.48] mmol/L in nondiabetics; P < 0.01], and the apolipoproteins A-I and B had significantly higher concentrations in type I DM. In umbilical venous cord blood, ratios of HDL-TC and HDL-PL to apo AI, reflecting the lipid content of HDL, were reduced when the mother had type I DM during pregnancy (P < 0.02 and P < 0.0001, respectively). These results indicate that maternal type I DM may lead to a fetal serum lipoprotein composition more closely resembling that seen in the adult. In type I DM, maternal TG and PL and fetal TC, TG, PL, CE, and FC were correlated to NEFA levels (P < 0.05), but not to glucose, insulin secretion, or maternal control of type I DM. These data suggest that the enhanced supply of NEFA to the fetus in type I DM pregnancies may drive the synthesis of cholesterol as well as TGs and PLs.     

Presence of immunoassayable beta-endorphin in human amniotic fluid: elevation in cases of fetal distress

Immunoassayable beta-endorphin is present in samples of amniotic fluid obtained in the last two weeks of pregnancy. Average concentration is approximately 300 pg. per milliliter. In all cases of suspected or recognized fetal distress, striking elevations of the beta-endorphin concentrations (twofold to 20-fold) were observed. The degree of elevation correlated with the degree of fetal distress.     

Low-level mosaicism for both trisomy 15 and monosomy-X in amniotic fluid cells confirmed in fetal tissues

We report here a case of true fetal mosaicism for both trisomy 15 and monosomy-X; the aberrant cell lines were initially detected at amniocentesis as low-level mosaicism (trisomy 15) and multiple-cell pseudo-mosaicism (monosomy-X). In the fetal lymphocytes, only metaphases with a normal chromosome complement were observed. After termination of the pregnancy, various fetal biopsies revealed both trisomy 15 and monosomy-X mosaicism, whereas, at autopsy, no external or internal abnormalities could be detected in the fetus. The karyotype can be described as 45,X[15]/47,XY,+15[3]/46,XY[27]. Our results implicate that an additional amniocentesis could be more helpful than fetal blood sampling in predicting the fetal karyotype after diagnosis of chromosome mosaicism at amniocentesis.     

Normal outcome of a pregnancy with mosaicism for double trisomy in amniotic fluid cells

True chromosomal mosaicism of double trisomy (48,XX, +7, +20) was detected in amniotic fluid cell cultures at 16 and 20 weeks of gestation. No aneuploid cells were found in chorionic villus samples (CVS) by semidirect preparation and long-term culture. High-level ultrasound did not indicate any structural abnormality of the fetus. At 38 weeks of gestation, a phenotypically normal girl was born. She is now 22 months old and normally developed. At birth, various samples were investigated by routine cytogenetic methods or by fluorescence in situ hybridization with the probe p7t1 (umbilical cord blood, placental tissue, umbilical cord fibroblasts, urine sediment) and no abnormal cells could be detected in any of those tissues.     

Erythropoietin and the inhibitor of erythropoiesis in the amniotic fluid during the first trimester of normal human pregnancy

The erythropoietic activity of the amniotic fluid from the 1st trimester of pregnancy and of blood plasma of pregnant women was tested biologically on polycythaemic mice by means of radiolabelled 59Fe. It was found that the amniotic fluid exhibits an erythropoietic activity. Then, using Sephadex G-100 gel filtration several fractions of the fluid were separated chromatographically; they were tested on polycythaemic mice for their erythropoiesis-stimulatory and inhibitory activity. It was found that fraction II proteins (mol. w. about 38 000) acted as an erythropoiesis stimulator, while fractions V and VI (mol. w. 6 900 and 4 000, respectively) showed inhibitory properties.     

Tubular fluid concentrations and kidney contents of angiotensins I and II in anesthetized rats

Previous micropuncture studies have reported nanomolar concentrations of angiotensin II in proximal tubular fluid and have indicated that angiotensin II or a precursor may be secreted into the tubular lumen. Further experiments were performed to determine if proximal tubular fluid angiotensin I concentrations are also greater than plasma and kidney levels and to estimate the degree of intrarenal compartmentalization of the angiotensin peptides. Free-flow proximal tubular fluid samples were collected in micropipets and were pooled for each animal. At the end of each experiment, a blood sample was collected and the micropunctured left kidney was harvested and homogenized in methanol. The angiotensin I concentration in proximal tubular fluid samples averaged 6.1 +/- 1.2 pmol/mL, whereas the angiotensin II concentration averaged 8.1 +/- 1.6 pmol/mL (N = 13). HPLC analysis of a separate sample pooled from collections in five rats indicated that the immunoreactive angiotensin I and angiotensin II primarily represented authentic angiotensin I and II. Plasma concentrations of angiotensin I and angiotensin II averaged 0.39 +/- 0.09 and 0.15 +/- 0.03 pmol/mL, respectively. The kidney contents of angiotensin I and angiotensin II were 1.28 +/- 0.24 and 0.97 +/- 0.17 pmol/g of kidney, respectively. These findings indicate that proximal tubular fluid contains nanomolar concentrations of angiotensin I as well as angiotensin II. These high tubular fluid concentrations, which greatly exceed the plasma and kidney levels, likely reflect net secretion of the angiotensin peptides by proximal tubule cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prenatal diagnosis of congenital toxoplasmosis: comparative value of fetal blood and amniotic fluid using serological techniques and cultures

The management of patients with acute, severe ulcerative colitis requires careful in-hospital assessment of the patient and the coordinated treatment of a team of experienced gastroenterologists and surgeons. Complete understanding of the potential complications and their management, especially toxic megacolon, is essential. We review the current medical arsenal and advocate a standardized approach to management that includes continuous, high dose intravenous hydrocortisone, more aggressive use of topical steroids as well as feeding the patients and continuing (but not initiating) oral 5-aminosalicylic acid (5-ASA) agents. For those patients whose disease proves refractory to intravenous steroids, intravenous cyclosporin (with an acute response rate of 82%) is an essential component in the medical management of these patients. Antibiotics should be used only when specifically indicated. Total parenteral nutrition has not been shown to be helpful in the acute setting. Air contrast barium enema and colonoscopy have been used to predict response but may be dangerous diagnostic modalities in these acutely ill patients and are no better than good clinical judgement. We review and advocate long-term management of acute response using 6-mercaptopurine or azathioprine. The surgical experience and the postoperative complications of the ileal pouch anal anastomosis, which include acute pouchitis in 50-60%, chronic pouchitis in 5-10% and recent reports of dysplasia among patients with chronic pouchitis, must be considered before colectomy is advised. Over 80% of patients with acute severe colitis can be spared colectomy using our current arsenal of medical therapies.     

Compliance of the lung-thorax system in pregnancy complicated by pre-eclampsia

Compliance of the lungs and thorax was studied in 65 pregnant women during cesarean section. The measurements were carried out in a group of healthy controls and in patients with preeclampsia. The detected changes indicated increased rigidity of the lungs even in normal pregnancy. Comparison of the results indicates an appreciable increase of rigidity of the lungs in patients with preeclampsia, this permitting us to regard it as a status involving interstitial pulmonary hyperhydration.     

Control of oocyte growth and maturation by follicular cells and molecules present in follicular fluid. A review

The aim of this review is to summarize the interactions between the oocyte and its surrounding granulosa cells which are involved in the control of oocyte growth or apoptosis as well as those playing a key role in the ability of the oocyte to undergo nuclear (resumption as meiosis to reach the MII stage) or cytoplasmic maturation (ability to fertilize and develop to the blastocyst stage). The respective roles of the oocyte and of the granulosa cells in controlling the initiation of growth are poorly understood. During the preantral follicular stage when most oocyte growth is achieved, a local regulation appears to be in operation involving growth factors such as fibroblast growth factor (FGF) or epidermal growth factor/transforming growth factor alpha (EGF/TGF alpha), together with two proteins (c-kit present on the oocyte's membrane and its ligand KL produced by granulosa cells). In-situ techniques used to detect apoptosis demonstrate apoptotic oocytes in the reserves of primordial follicles but seldom within preantral follicles (because it is too fast?). Proteins involved in cell death (bax) or cell survival (bcl2) are present in oocytes as well as compounds (TNF alpha, Fas) involved in the initiation of apoptosis. However, the molecular and cellular mechanisms triggering oocyte apoptosis are not fully clarified. Three approaches have been used to identify compounds which are relevant to the oocyte's nuclear or cytoplasmic maturation. a) Correlation between amounts of specific compounds in follicular fluid or within follicle cells and the oocyte's ability to mature. b) Analysis of the consequences of pharmacological disruption of mechanisms such as steroidogenesis on oocyte maturation. c) Analysis of the consequences of addition of graded amounts of specific compounds on oocyte maturation in defined media. Factors playing a key role in stimulating nuclear maturation appear to be epidermal growth factor (EGF) and the inhibin (cattle)/activin (rodents) family, while testosterone has an inhibitory effect. Cytoplasmic maturation of the oocyte appears to be stimulated by oestradiol, EGF and inhibin.     

Hand preference and components of I.Q

An account is given of the hand preferences (measured by questionnaire) of 687 individuals living in a Cambridge suburb. The proportions of right, mixed and left handers differed according to the classification used. Verbal and Performance I.Q. component scores were examined in relation to hand preference. For all classifications, left handers' overall Verbal I.Q. was significantly higher than their Performance I.Q. score, whereas right and mixed handers' Performance I.Q. scores were greater than their Verbal I.Q.s. Left handers scored higher than right and mixed handers on Verbal I.Q. but lower on Performance I.Q. The relationships between patterns of handedness, I.Q. component scores and cerebral dominance are discussed.     

Accelerated maturation of fetal ductus arteriosus by maternally administered vitamin A in rats

STUDY OBJECTIVE: Examination of alcohol consumption patterns of male spectators at two major-league baseball stadiums. METHODS: A prospective observational study was conducted at two stadiums over the course of three games at each venue. We approached 1,084 male spectators of drinking age in a consecutive fashion at two junctures: at the entrance gate and during the fifth inning inside the stadium's concourse. Of those approached, 747 (68.9%) participated. After verbal consent, participants completed a questionnaire and blew into a breath analyzer. The results were blinded and later analyzed. RESULTS: Forty-one percent of all participants tested positive for alcohol. The highest consumption occurred in the 20- to 35-year-old age group. In this age group, 50.8% had consumed some alcohol, and 10.8% had a blood alcohol level of .08% (intoxicated) or higher. Almost 5% of all participants tested during the fifth inning collection were intoxicated and claimed to be driving. CONCLUSION: Of the spectators tested, those in the 20- to 35-year-old age group were most likely to have consumed alcohol and to be legally intoxicated. A disturbing number of spectators who had blood alcohol levels of .08% or higher late in the game claimed to be driving home.