Anticodon domain methylated nucleosides of yeast tRNA(Phe) are significant recognition determinants in the binding of a phage display selected peptide.

The contributions of the natural modified nucleosides to RNA identity in protein/RNA interactions are not understood. We had demonstrated that 15 amino acid long peptides could be selected from a random phage display library using the criterion of binding to a modified, rather than unmodified, anticodon domain of yeast tRNA(Phe) (ASL(Phe)). Affinity and specificity of the selected peptides for the modified ASL(Phe) have been characterized by fluorescence spectroscopy of the peptides' tryptophans. One of the peptides selected, peptide t(F)2, exhibited the highest specificity and most significant affinity for ASL(Phe) modified with 2'-O-methylated cytidine-32 and guanosine-34 (Cm(32) and Gm(34)) and 5-methylated cytidine-40 (m(5)C(40)) (K(d) = 1.3 +/- 0.4 microM) and a doubly modified ASL(Phe)-Gm(34),m(5)C(40) and native yeast tRNA(Phe) (K(d) congruent with 2.3 and 3.8 microM, respectively) in comparison to that for the unmodified ASL(Phe) (K(d) = 70.1 +/- 12.3 microM). Affinity was reduced when a modification altered the ASL loop structure, and binding was negated by modifications that disfavored hairpin formation. Peptide t(F)2's higher affinity for the ASL(Phe)-Cm(32),Gm(34),m(5)C(40) hairpin and fluorescence resonance energy transfer from its tryptophan to the hypermodified wybutosine-37 in the native tRNA(Phe) placed the peptide across the anticodon loop and onto the 3'-side of the stem. Inhibition of purified yeast phenylalanyl-tRNA synthetase (FRS) catalyzed aminoacylation of cognate yeast tRNA(Phe) corroborated the peptide's binding to the anticodon domain. The phage-selected peptide t(F)2 has three of the four amino acids crucial to G(34) recognition by the beta-structure of the anticodon-binding domain of Thermus thermophilus FRS and exhibited circular dichroism spectral properties characteristic of beta-structure. Thus, modifications as simple as methylations contribute identity elements that a selected peptide specifically recognizes in binding synthetic and native tRNA and in inhibiting tRNA aminoacylation.

Effect of fetal hyperinsulinism on oral glucose tolerance test results in patients with gestational diabetes mellitus.

OBJECTIVE: This study was undertaken to evaluate the impact of the fetoplacental glucose steal phenomenon on the results of oral glucose tolerance testing in pregnancies complicated by gestational diabetes mellitus with fetal hyperinsulinism. STUDY DESIGN: This was an analysis of the cases of 34 patients with two consecutive abnormal oral glucose tolerance test results and amniotic fluid insulin measurement before institution of insulin therapy. Patients were divided into groups on the basis of normal versus elevated amniotic fluid insulin concentrations. RESULTS: Oral glucose tolerance tests were done at a mean (+/-SD) of 24.9 +/- 5.7 and 30.7 +/- 3.2 weeks' gestation, and amniotic fluid insulin measurements were done at 31.1 +/- 3.2 weeks' gestation. In 13 women with gestational diabetes mellitus with normal amniotic fluid insulin concentration, maternal postload blood glucose levels at 1 hour increased by 12 mg/dL (168 vs 180 mg/dL; 9.3 vs 10.0 mmol/L; P = .0006) during the course of 6 weeks. In contrast, in 21 women with gestational diabetes mellitus with elevated amniotic fluid insulin levels (>7 microU/mL; >42 pmol/L), 1-hour postload blood glucose levels decreased by 22 mg/dL (201 vs 179 mg/dL; 11.2 vs 9.9 mmol/L; P = .002) during the same period. The higher the amniotic fluid insulin level, the larger the decrease (R = 0.504; P =.02). Although low amniotic fluid insulin levels were correlated significantly with 1-hour glucose levels of the first and second oral glucose tolerance tests, high insulin levels were no longer correlated with the second oral glucose tolerance test. CONCLUSION: Exaggerated fetal glucose siphoning may provide misleading oral glucose tolerance test results in pregnancies complicated by fetal hyperinsulinism by blunting maternal postload glucose peaks. Consequently, oral glucose tolerance test results in a pregnancy complicated by gestational diabetes mellitus with a fetus that already has hyperinsulinemia may erroneously be considered normal.

Cord blood oxygen saturation in vigorous infants at birth: what is normal?

OBJECTIVE: To define the normal ranges of umbilical cord blood oxygen saturation (SaO2) and acid-base status at birth and to evaluate the effect of gestational age on cord blood values in vigorous newborn infants following spontaneous vaginal birth from a vertex position. DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynaecology, University of Graz, Austria. SAMPLE: Cord blood samples from 1281 vigorous newborn infants. METHODS: Cord blood sampling was performed following on newborn infants following spontaneous vaginal birth in a vertex position. SaO2 was measured directly by a spectrophotometer and pH, base excess, pCO2 and pO2 by a pH/blood-gas analyser. Infants with a 5-minute Apgar score > or = 7 were considered vigorous. Subgroups were classified according to the gestational age: preterm, term and post-term (< 37, 37-42 and > 42 weeks, respectively). RESULTS: The median umbilical artery SaO2 was 24.3% and the 2.5th centile was as low as 2.7%. The median umbilical artery values were pH = 7.25, base excess = -4.3 mmol/L and pO2 = 16 mmHg. The 2.5th centiles were 7.08, -11.1 mmol/L and 5 mmHg, respectively. The median umbilical artery pCO2 was 50 mmHg and the 97.5th centile was 75 mmHg. The mean umbilical artery and vein SaO2 values were not significantly influenced by gestational age. The umbilical artery SaO2 and base excess values were strongly skewed. The mean umbilical artery pH values in preterm infants were higher than in other subgroups. The mean umbilical artery and vein base excess values were lower in post-term newborn infants than in other subgroups. CONCLUSIONS: The physiological range of oxygen saturation in umbilical cord of vigorous newborn infants at birth is wide and skewed. In contrast to pH and base excess, umbilical cord blood oxygen saturation is not influenced significantly by gestational age at birth.

Long-term follow-up of infants of mothers with type 1 diabetes: evidence for hereditary and nonhereditary transmission of diabetes and precursors.

OBJECTIVE: To estimate the impact of type 1 diabetes during pregnancy on transgenerational genetically caused and/or fuel-mediated amplification of types 1 and 2 diabetes and to estimate the impact of elevated amniotic fluid insulin levels. RESEARCH DESIGN AND METHODS: A total of 75 white offspring of type 1 diabetic mothers and 49 control subjects of similar age and pubertal stage were examined at 5-15 years of age. All offspring had an oral glucose tolerance test. Glucose, insulin, and C-peptide were measured at 0, 30, 60, and 120 min after loading. Lipids and autoimmune antibodies were measured in fasting plasma. RESULTS: Of the 75 offspring, 4 (5.3%) had overt diabetes, and 16 of 71 (22.5%) had autoimmune antibodies. Offspring of diabetic mothers had significantly higher BMI; symmetry indexes; cholesterol, glucose, insulin, and C-peptide levels; and insulin resistance than control subjects. With the exception of cholesterol, these values were significantly elevated in offspring who had elevated amniotic fluid insulin levels (>8 microU/ml, >48 pmol/l) during pregnancy compared with normoinsulinemic offspring and control subjects. CONCLUSIONS: Offspring of type 1 diabetic mothers have an increased risk for diabetes later in life. The relative risk for type 1 and type 2 diabetes is 71.6 and 3.2, respectively. Type 2 diabetes-associated risk factors, such as high BMI; elevated glucose, insulin, and C-peptide levels; and insulin resistance, are related to the fetal metabolic experience in utero, as reflected by amniotic fluid insulin concentration.

Low fetal oxygen saturation at birth and acidosis.

OBJECTIVE: To measure umbilical cord blood oxygen saturation, to calculate preductal oxygen saturation at birth, and to assess its predictive value for acidosis. METHODS: Umbilical cord blood samples of 1537 live-born singleton neonates were analyzed. Oxygen saturation was measured by spectrophotometry; pH and base excess were measured by a pH and blood gas analyzer. Preductal oxygen saturation was calculated with an empirical equation. Acidosis was defined as 2 standard deviations (SDs) below the mean of umbilical artery (UA) pH or base excess (7.09 and -10.50 mmol/L, respectively). The predictive value for acidosis of UA and umbilical vein (UV) oxygen saturation and calculated preductal oxygen saturation was determined with receiver operating characteristic curves. RESULTS: The mean values (+/-SD) of UV, UA, and calculated preductal oxygen saturation were 52 +/- 18%, 26 +/- 17%, and 31 +/- 16%, respectively. Forty-seven neonates had UA pH less than 7.09 and 60 had UA base excess less than -10.50 mmol/L. The UV, UA, and calculated preductal oxygen saturation showed considerably weaker relations to UA base excess (multiple r(2) =.056,.003, and.017, respectively; P <.001) than to UA pH (multiple r(2) =.112,.126, and.148, respectively; P <. 001). Receiver operating characteristic areas under the curve were higher when predicting low pH compared with low base excess (for UV, UA, and calculated preductal oxygen saturation: 0.716 versus 0.699, 0.747 versus 0.586, and 0.765 versus 0.628, respectively). The difference was significant for UA oxygen saturation (P <.05). All tests showed high sensitivity and negative predictive values, but low specificity and positive predictive values. CONCLUSION: Low fetal oxygen saturation measured at birth seemed to be associated with low fetal pH and base excess values, but its predictive value for acidosis in an unselected population was limited, particularly if acidosis was metabolic.

Can glucose tolerance test predict fetal hyperinsulinism?

OBJECTIVE: To establish cut off levels for oral glucose tolerance test in pregnancy using fetal hyperinsulinism as a clinical endpoint. DESIGN: Capillary blood glucose levels at 0, 1, and 2 hours after the ingestion of either 1 g/kg or 75 g glucose, at 28 (SD 5) weeks of gestation were analysed in 220 women with elevated amniotic fluid insulin levels [> or =42 pmol/L (> or =7 microU/mL)] after a mean (SD) of 31 weeks (3) and in 220 nondiabetic controls. RESULTS: In women with elevated amniotic fluid insulin levels the mean (SD) capillary blood glucose values at 0, 1, and 2 hours were 5.2 mmol/L (1.0) [94 mg/dL (18)], 10.5 mmol/L (1.4) [189 mg/dL (25)] and 8.2 mmol/L (2.0) [147 mg/dL (36)], respectively. The one-hour value had the highest sensitivity to predict elevated amniotic fluid insulin levels. The 5th centile of the one-hour blood glucose levels representing a detection rate of 95% was 8.9 mmol/L (160 mg/dL). CONCLUSION: Glucose cut off levels in most established oral glucose tolerance test criteria are too high, to accurately predict amniotic fluid hyperinsulinism. A one-hour test may be sufficient for detecting amniotic fluid hyperinsulinism. Since different loads (1 g/kg, 75 g or 100 g) and blood fractions (venous plasma or capillary blood) have minimal impact on oral glucose tolerance test results, a single one-hour cut off of 8.9 mmol/L (160 mg/dL), independent of the sampling method, may be appropriate for the diagnosis of gestational diabetes mellitus severe enough to cause amniotic fluid hyperinsulinism.

Course of maternal serum magnesium levels in low-risk gestations and in preterm labor and delivery.

OBJECTIVES: To describe the course of total and ionized magnesium and total calcium levels in maternal serum during low-risk pregnancies and to compare women who developed preterm labor and delivery with those who delivered at term. METHODS: 209 women with low-risk pregnancies were enrolled in a prospective trial before the 18th week of gestation. No woman received oral magnesium supplementation. The ionized and total magnesium and total calcium levels in maternal serum were measured every 4-6 weeks. The data were grouped into 3 gestational periods (/=28 weeks of gestation) for overall comparison and analyzed with the general linear model for repeated measurements and ANOVA. p values of < 0.05 were considered statistically significant. RESULTS: 145 gestations were available for analysis. 27 women were hospitalized for preterm labor and in 16 of these preterm delivery occurred. Ionized and total magnesium and calcium levels were significantly lower after the 18th week of gestation than before. The cation levels in women with preterm labor and delivery did not differ from those with term delivery. CONCLUSION: Ionized and total magnesium and calcium levels decrease with increasing gestational age. Preterm labor and delivery do not seem to be related to changes in serum cation levels.

Amniotic fluid insulin levels in nondiabetic pregnant women: an update.

Elevated amniotic fluid insulin levels in diabetes are frequently described but there are few systematic data on metabolically healthy women to define normal ranges. Previous studies had too high normal ranges because they were based on unspecific insulin binding radioimmunoassays. The aim of the study was to update normal amniotic fluid insulin data and to define a reliable normal range in the course of a nondiabetic pregnancy. Amniotic fluid insulin levels were measured in 841 amniotic fluid samples of 707 nondiabetic women undergoing amniocentesis for hydramnios, suspected malformation, determination of lung maturation, Rhesus antibodies and cordocentesis. Mean (+/- SD) of amniotic fluid insulin level was 3.6 (+/- 2.1) microU/mL at 31.5 (+/- 4.9) weeks of pregnancy. The 97th percentile was 8.2 microU/mL. Insulin levels show a biphasic course between 16th and 42nd weeks of pregnancy with a zenith at 30th week. Only two cases (0.3%) had unexplicably elevated amniotic fluid insulin levels > or = 10 microU/mL. Thus, in nondiabetic women amniotic fluid insulin levels > 10 microU/mL are unlikely.

Amniotic fluid insulin testing in gestational diabetes: safety and acceptance of amniocentesis.

OBJECTIVES: We analyzed the safety and patient acceptance of amniotic fluid insulin measurements by third-trimester amniocentesis in women with gestational diabetes mellitus. STUDY DESIGN: We studied the rate of early uterine contractions, need for tocolysis, premature rupture of membranes, mode of delivery, length of gestation, and fetal weight and length at birth in 194 women with gestational diabetes mellitus who underwent third-trimester amniocentesis and 268 controls. Patient acceptance of amniocentesis was assessed prospectively with a visual rating scale and a semistructured interview comparing 50 women with gestational diabetes mellitus to 50 women undergoing second-trimester amniocentesis for fetal karyotyping. RESULTS: Only the length of gestation differed significantly but without clinical relevance (39.5 +/- 1.9 vs 40.0 +/- 2.0, P = .006) between women with gestational diabetes mellitus who had amniocentesis and controls. Patient acceptance was equally high both for second-trimester and third-trimester amniocentesis. CONCLUSIONS: Third-trimester amniocentesis for measuring amniotic fluid insulin is safe and well accepted by the patients. This is important information both for treating and counseling women with gestational diabetes mellitus.

Cord blood insulin to assess the quality of treatment in diabetic pregnancies.

According to the Pedersen hypothesis, fetal hyperinsulinism is the major cause for adverse neonatal outcome. We investigated associations between insulin levels in cord blood and fetal complications. Three groups of 21 insulin-dependent diabetic patients with different insulin levels in cord blood were matched according to White Classes. Insulin levels in cord blood of < 20 microU/ml were considered normal (controls), 20-50 microU/ml intermediate group, and > 50 microU/ml high (cases). The mean (+/-S.D.) insulin level in cord blood in the three groups was 10.7+/-5.6, 28.6+/-8.1, and 104.0+/-61.0 microU/ml, respectively. Controls and cases showed significant differences in birth weight > 90th percentile (9.5% vs. 76.2%), premature birth < 37 weeks (4.8% vs. 71.4%), caesarean delivery (28.6% vs. 66.4%), hypoglycaemia of the neonate (14.3% vs. 61.9%), cushingoid appearance (4.8% vs. 42.9%) and respiratory distress syndrome (0% vs. 33.3%). The results of the intermediate group were between the controls and the cases. Insulin levels in cord blood > 20 microU/ml represent a continuum of increasing diabetogenic fetopathy. We consider neonates with insulin levels in cord blood < 20 microU/ml as metabolically healthy, those with 20-50 microU/ml as having mild fetopathy, and those with > 50 microU/ml as having marked fetopathy, respectively.

Effect of ethanol on B cell expression of major histocompatibility class II proteins in immunized mice.

Acute or chronic exposure to ethanol (EtOH), as well as other stimuli that induce a neuroendocrine stress response, can decrease the expression of MHC class II proteins (immune-associated antigens, Ia) on B cells and macrophages. In a mouse model for binge drinking, it has been shown that this decrease is caused by EtOH-induced increases in endogenous glucocorticoids. Decreased Ia expression would be expected to suppress T-dependent humoral responses, and such suppression has been noted in our model. However, it has been reported that activated B cells are much less susceptible to glucocorticoid-induced decreases in Ia expression than are resting B cells. Thus, it is not clear that the decreased Ia observed in our previous studies with non-immunized mice could account for decreased humoral responses, because it has not been directly determined that decreased Ia expression occurs in immunized mice. To examine this issue, splenocytes from mice immunized with sheep erythrocytes were studied by flow cytometry. Mice were treated with EtOH by gavage and immunized 12 h later, because our previous results indicate that this produces maximal suppression of the humoral response. In immunized mice, EtOH decreased Ia expression on B cells at 6 and 12 h after immunization, but not at 24 or 74 h. In a dose-response study, a substantial decrease in Ia expression on B cells was observed at an EtOH dosage of 6.0 or 7.0 g/kg. Thus, decreased Ia expression is a potential mechanism for EtOH-induced suppression of the humoral response. A glucocorticoid antagonist (RU 486) partially blocked the EtOH-induced decrease in Ia expression, suggesting that glucocorticoids are involved in the reduction of Ia expression in immunized mice. Direct administration of corticosterone to produce blood levels comparable to those noted in EtOH-treated mice did not significantly decrease Ia expression, but Ia expression tended to be lower in mice treated with corticosterone. Taken together, these results indicate that glucocorticoids play some role in decreasing Ia expression in immunized mice, but they are less important than in non-immunized mice.

Toward universal criteria for gestational diabetes: relationships between seventy-five and one hundred gram glucose loads and between capillary and venous glucose concentrations.

OBJECTIVES: Replacement of the two-step, 100 gm, 3-hour National Diabetes Data Group procedure by the one-step, 75 gm, 2-hour World Health Organization oral glucose tolerance test has been hindered by a paucity of data comparing the two tests during pregnancy. The current series compared 100 gm and 75 gm glucose loads and glucose measurements in venous plasma or capillary blood. STUDY DESIGN: After a 75 gm oral glucose tolerance test 30 gestational diabetics and 30 metabolically healthy pregnant women were randomly assigned to a second 75 or 100 gm test within 3+/-1.3 (mean+/-SD) days. Glucose levels at both tests was measured in capillary blood and venous plasma, as were insulin and C peptide. RESULTS: In controls 1-hour maternal glucose levels (112 vs 128 mg/dl) and 2-hour levels (104 vs 113 mg/dl) differed significantly after a 75 or 100 gm load (paired t test). In gestational diabetes mellitus, however, there was no difference (176 vs 178 mg/dl) but a low insulin/glucose quotient at 1 hour. Only 2-hour levels differed significantly (133 vs 149 mg/dl). In controls glucose measurement in capillary blood and venous plasma differed significantly at 1 hour (126 vs 115 mg/dl) and 2 hours (111 vs 104 mg/dl) independently of the glucose load. In gestational diabetes mellitus, however, glucose measurement in capillary blood and venous plasma differed neither in 1-hour levels (179 vs 174 mg/dl) nor in 2-hour levels (142 vs 139 mg/dl). CONCLUSION: In metabolically healthy women both different loading and different blood fractions lead to statistically different blood glucose levels at 1 and 2 hours. In gestational diabetes mellitus, however, 1-hour glucose levels do not differ after a 75 or 100 gm load or after glucose measurement in capillary blood or venous plasma. This is due to elevated insulin resistance shown by a low insulin/glucose quotient at 1 hour. For comparison of tests in gestational diabetes mellitus only, 2-hour values must be adjusted by 16 mg/dl after different loading.

Anti-insulin antibodies and birth weight in pregnancies complicated by diabetes.

Free insulin cannot cross the placenta but insulin complexed to anti-insulin antibodies has been demonstrated in cord blood. We studied whether antibody-bound insulin in diabetic patients can evoke fetal macrosomia independently of maternal metabolic control. In 457 non insulin-treated controls and 173 insulin-treated diabetic patients we measured 1187 anti-insulin antibody levels and maternal blood glucose, maternal fructosamine, cord blood insulin, cord blood C-peptide, cord blood fructosamine and amniotic fluid insulin. Mean anti-insulin antibody levels in maternal blood and cord blood were significantly higher in insulin treated diabetic patients (4.6 and 5.4 U/ml) than in controls (1.8 and 1.7 U/ml) with maxima of 89.2 in maternal and 120.0 U/ml in cord blood, respectively. In insulin treated diabetic patients 16.6% (maternal blood) and 22% (cord blood) anti-insulin antibody levels were above the 97th percentile. There was a high significant correlation between maternal and cord blood anti-insulin antibodies (R = 0.987, P = < 0.0001), but no correlation of anti-insulin antibodies with maternal (glucose, fructosamine) or fetal (insulin, C-peptide, and fructosamine in cord blood, amniotic fluid insulin) metabolic parameters. While maternal and fetal metabolic parameters correlated with birth weight neither maternal nor cord blood anti-insulin antibody levels correlated with birth weight. These findings do not support the hypothesis that maternal anti-insulin antibodies independently influence fetal weight.

Levels of amniotic fluid insulin and profiles of maternal blood glucose in pregnant women with diabetes type-I.

The aim of this study was to investigate the relationship between amniotic fluid insulin (AF-insulin) measurements and maternal blood glucose levels in pregnancies complicated by insulin-dependent maternal diabetes mellitus (IDDM). Twenty-five patients with IDDM underwent amniocentesis (AC) in the third trimester. Twelve patients had a second amniocentesis after 2-3 weeks. The maternal blood glucose values (MBG) 2 weeks before amniocentesis were correlated with AF-insulin. Mean (+/-S.D.) MBG in the group with AF-insulin > 97th centile (n = 7) was 6.1 +/- 1 mmol/l. MBG in the group with AF-insulin < 97th centile (n = 18) was 5.3 +/- 1.2 mmol/l (r = 0.2948; P-value 0.162). In the group with repeated AC and AF-insulin > 97th centile (n = 6) the correlation coefficient was 0.722 (P = 0.043), whereas in the group with normal AF-insulin (n = 6) no correlation was found (r = -0.213; P = 0.686). These results indicate that no significant correlation exists between MBG values and concentration of AF-insulin. MBG is not appropriate for the diagnosis of fetal hyperinsulinism in well-controlled women with IDDM. In individual cases with AF-insulin > 97th centile a decrease of MBG causes lower AF-insulin levels. These results indicate that there seems to be an individual threshold for maternal MBG which causes hyperinsulinism. Fetal hyperinsulinism not only depends on blood glucose levels. Different fetal sensitivity to maternal glucose stimuli or a different glucose transport across the placenta in the individual fetus could be responsible for these results.

Ultrasound growth parameters in relation to levels of amniotic fluid insulin in women with diabetes type-I.

The aim of the study was to investigate the correlation between ultrasound parameters and levels of amniotic fluid insulin (AF-insulin) in pregnancies complicated by insulin-dependent diabetes mellitus (IDDM). In 129 women with IDDM amniocentesis was performed between 28 and 35 weeks of gestation. The levels of AF-insulin were measured by radioimmunoassay (Pharmacia RIA 100) and were correlated with biparietal diameter (BPD), abdominal diameter (AD), abdominal circumference (AC), and femur length (FL). The women were maintained at good glycemic control (fructosamine level: mean +/- S.D.: 236.3 +/- 40 micromol/l) and delivered infants with a mean (+/- S.D.) birth weight of 3477 +/- 640 g. The sensitivity of BPD, AD, AC and FL to detect fetuses with pathological levels of AF-insulin was 50%, 62%, 67% and 49%, respectively. The sensitivities of AD and AC in a selected group (n = 14) with highly pathological levels of AF-insulin (> 20 microU/ml) were both 80%, whereas the specificity was 56% and 46%, respectively. In women with IDDM, fetal biparietal diameter, abdominal diameter, abdominal circumference, and femur length are not reliable markers for the identification of fetal hyperinsulinism. Only cases with highly pathological levels of AF-insulin can be detected by abdominal measurements.

[Fetal ultrasound biometry and amniotic fluid insulin concentration in pregnant diabetic patients]. / Fetale Ultraschallbiometrie und Fruchtwasserinsulinkonzentration bei diabetischen Schwangeren.

OBJECTIVE: The aim of the study was to prove the sensitivity of sonographic measurements for the presence of a fetal hyperinsulinism. METHODS: In a longitudinal examination of 102 insulin-dependent diabetics we show the correlation between the amniotic fluid insulin level and the biparietal diameter, abdominal diameter and femur length in the third trimester. The control of the maternal metabolic state was done by measuring the glycosylated hemoglobin and fructosamine at the time of the amniocentesis. RESULTS: The sensitivity, specificity, positive and negative predictive value of sonographic measurements > 75th percentile in fetal hyperinsulinism was for the biparietal diameter 21, 96, 81 and 62%, for the abdominal diameter 48, 82, 69 und 66%, and for the femur length 22, 90, 67 and 57%. The maternal glycoproteins did not show any correlation with the amniotic fluid insulin level. CONCLUSIONS: The results demonstrate that fetal hyperinsulinism cannot be proved by fetal biometry or evaluation of the maternal metabolic state.

Role of glucocorticoids in ethanol-induced decreases in expression of MHC class II molecules on B cells and selective decreases in spleen cell number.

Glucocorticoids have been implicated in some of the immunosuppressive effects associated with acute ethanol (EtOH) intoxication, but other neuroendocrine mediators that are induced by EtOH can also be immunosuppressive. The possibility that glucocorticoids may act additively or synergistically with other mediators to produce immunosuppression has not been fully investigated. In the present study, complementary methods were used to address this issue. EtOH dose-responsively decreased the following parameters in the spleen in B6C3F1 mice: total cell number, mature B cell (IgM+IgD+) number, and expression of MHC class II molecules on B cells. These effects were most pronounced 12 hr after administration of EtOH. The glucocorticoid antagonist, RU 486, completely or partially blocked these effects. Thus, glucocorticoids seem necessary for full expression of these immunological changes in EtOH-treated mice. To determine if glucocorticoids are also sufficient to cause these effects, corticosterone was administered to achieve serum levels and kinetics comparable to those in EtOH-treated mice. This decreased the expression of MHC class II molecules on B cells to the same extent as treatment with EtOH. However, the other parameters were not affected by administration of corticosterone. Thus, corticosterone is necessary and sufficient to decrease expression of MHC class II molecules on splenic B cells, but other mediators in addition to corticosterone are required to decrease total spleen cell number and the number of mature B cells in the spleen.

[A rapid method for diabetes screening in pregnancy]. / Schnellmethode zum Diabetesscreening in der Schwangerschaft.

Gestational diabetes affects about 3% of pregnancies in German-speaking countries. Roughly one third of these pregnancies develop a requirement of insulin. In unrecognised and hence untreated pregnancies, perinatal morbidity and mortality are increased 20-fold. Gestational diabetes is asymptomatic and only 60% of patients have risk factors for the condition; thus, general screening with oral glucose tolerance testing is necessary to detect all cases. Most antenatal medical care is provided by gynaecologists in practice and by general practitioners who do not have a sophisticated laboratory at their immediate disposal. General screening requires a test that is simple, inexpensive and quick but nonetheless meets high quality standards. A new microcuvette rapid test fulfills these requirements; the results are ready within a few minutes' time. We performed parallel blood glucose measurements with a standard enzymatic method and with the rapid test in 500 unselected pregnant women undergoing an oral glucose tolerance test at our obstetric clinic. The mean fasting, 1-hr and 2-hr values were 77,128 and 106 mg/dl, respectively, as measured by the enzymatic test and 75,129 and 107 mg/dl as measured by the rapid test. The results of the reference enzymatic method and the rapid test agreed at a high level of significance (r = 0.98; p < 0.0001).

[Premature labor and fetal fibronectin in cervical and vaginal secretions]. / Frühgeburt und fetales Fibronectin im Zervikal- und Vaginalsekret.

This study aimed to determine whether quantitative measurements of fetal fibronectin in cervical vaginal secretions reflect the prognosis for imminent premature delivery. 166 patients, who were pregnant from between 25 and 36 weeks, were included in the study over a six months' period. Group A included 60 women with premature contractions, which ceased after tocolytic therapy. Group B consisted of 25 women, who delivered prematurely within 1 week. Group C contained 22 patients, with confirmed PROM and group D contained 24 patients in whom PROM was suspected, but not confirmed. The control group (group E) consisted of 35 patients with uneventful pregnancies. Fetal fibronectin levels in groups B and C differed significantly from those in the other groups. Therefore, the positive predictive value of elevated fetal fibronectin levels for premature delivery was 86.1%.

Insulin receptor binding to erythrocytes in the first half of pregnancy is increased in healthy pregnant women as compared with non-pregnant or gestational diabetic women.

Insulin binding to erythrocytes was measured longitudinally by a competitive radioreceptor assay in 21 healthy pregnant (HP) and 20 well-controlled gestational diabetic women (GD) in 4-week intervals throughout pregnancy and at day 4 post-partum. Maximum insulin binding (maxbdg) at weeks 8-14 was increased (P < 0.001) in HP (median: 6.0%) but not in GD (median: 2.7%) as compared with non-pregnant control subjects (C) (median: 3.6%; previously reported: Clin. Chim. Acta 1992;207:57-71) due to an increased number of high-affinity insulin receptors. Throughout gestation the binding decreased continuously, to reach at term the levels found in C. In GD maxbdg remained close to the level of C throughout pregnancy. Binding differences between HP and GD were independent of the body mass index. Maxbdg did not differ between diet- and insulin-treated patients. It was higher in women whose offspring had low umbilical cord insulin levels (< 10 mu units/ml). The findings suggest that (a) higher insulin binding in HP could contribute to the improved glucose tolerance in early pregnancy and (b) the lack of increase in insulin binding during early pregnancy in gestational diabetes might be one factor leading to the manifestation of the disease in late pregnancy. However, it must be kept in mind that insulin receptors on erythrocytes do not necessarily resemble those on the major target tissues of insulin.