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O Langer

Publications and source records attributed to O Langer.

At least 37 records · Page 2Linked to original sources
PubMed2000

Carbon-11 pb-12: an attempt to visualize the dopamine d(4) receptor in the primate brain with positron emission tomography.

The dopamine D(4) receptor (D(4)R) is expressed in low density in various extrastriatal brain regions. This receptor subtype is discussed in relation to the pathophysiology and treatment of schizophrenia but no selective positron emission tomography (PET) ligand is available to date to study the distribution in vivo. The arylpiperazine derivative N-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide (PB-12) is a novel, high-affinity ( K(i)=0.040 nM) and selective D(4)R ligand. We radiolabeled PB-12 with carbon-11 (t(1/2) 20.4 min) by O-methylation of the corresponding desmethyl analogue N-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-3-hydroxybenzamide (LM-190) with [(11)C]methyl triflate. Derivative LM-190 was prepared by condensing 3-hydroxybenzoic acid with the appropriate amine. For the radiolabeling, the incorporation yield was >90% and the total synthesis time including high performance liquid chromatography (HPLC) purification was about 35 min. The specific radioactivity of [(11)C]PB-12 at time of injection was 67-118 GBq x micromol(-1). PET studies in a cynomolgus monkey showed a high uptake and widespread distribution of radioactivity in the brain, including the neocortex and thalamus. About 40% of total radioactivity in plasma represented unchanged radioligand at 60 min after injection as determined by HPLC. Pretreatment with the D(4)R ligand 3-[[4-(4-chlorophenyl)piperazin-1-yl]methyl]-1H-pyrollo[2,3-b]pyridine (L-745,870) prior to radioligand injection failed to demonstrate receptor-specific binding in the monkey brain. Furthermore, the brain radioactivity distribution was left unaffected by pretreating with unlabeled PB-12. This failure to detect a D(4)R-specific signal may be related to a very low density of the D(4)R in primate brain, insufficient binding affinity of the radioligand, and a high background of nonspecific binding. It can be concluded from these findings that [(11)C]PB-12 is not suitable to visualize the D(4)R in the primate brain with PET.

Animals↗
PubMed2000

Vaginal fetal fibronectin measurements from 8 to 22 weeks' gestation and subsequent spontaneous preterm birth.

OBJECTIVE: We sought to determine the range of fetal fibronectin values in the vagina from 8 to 22 weeks' gestation, the factors associated with both low and high values, and whether high values are associated with gestational age at birth. STUDY DESIGN: Vaginal fetal fibronectin was quantitatively determined in a prospective cohort study of 13,360 women being evaluated for participation in the National Institute of Child Health and Human Development Maternal-Fetal Medicine Unit treatment trials for bacterial vaginosis and Trichomonas vaginalis. Fetal fibronectin values were correlated with gestational age at screening, race, the presence of bacterial vaginosis and Trichomonas vaginalis, and gestational age at delivery. RESULTS: Vaginal fetal fibronectin values at each gestational age ranged from unmeasurable to >1000 ng/mL, with median values always being <10 ng/mL. Fetal fibronectin values declined progressively with increasing gestational age at sampling. Bacterial vaginosis and black race were associated with higher values, whereas nulliparity was associated with lower values. High values after 13 weeks' gestation were associated with a 2- to 3-fold increased risk of subsequent spontaneous preterm birth overall and a 4-fold increased risk of very early preterm birth. CONCLUSION: Elevated vaginal fetal fibronectin levels from 13 to 22 weeks' gestation are associated with a significantly increased risk of spontaneous preterm birth.

Black People↗
PubMed2000

Fetal macrosomia: etiologic factors.

Fetal growth can be considered the outcome of an interaction between the genetic cause of growth and constraints provided by limitations on substrate availability (selected amino acids, free fatty acids, and mainly glucose). It should be noted that the majority of large infants are constitutionally large and do not require special intervention, which will result in adverse perinatal outcome. Efforts should be directed to the accelerated (pathologic) overgrown fetus and to methods of primary prevention of this abnormality by appropriate management approaches for the mother and fetus.

Female↗
PubMed1999

Absolute quantitation of iodine-123 epidepride kinetics using single-photon emission tomography: comparison with carbon-11 epidepride and positron emission tomography.

Epidepride labelled with iodine-123 is a suitable probe for the in vivo imaging of striatal and extrastriatal dopamine D2 receptors using single-photon emission tomography (SPET). Recently, this molecule has also been labelled with carbon-11. The goal of this work was to develop a method allowing the in vivo quantification of radioactivity uptake in baboon brain using SPET and to validate it using positron emission tomography (PET). SPET studies were performed in Papio anubis baboons using 123I-epidepride. Emission and transmission measurements were acquired on a dual-headed system with variable head angulation and low-energy ultra-high resolution (LEUHR) collimation. The imaging protocol consisted of one transmission measurement (24 min, heads at 90 degrees), obtained with two sliding line sources of gadolinium-153 prior to injection of 0.21-0.46 GBq of 123I-epidepride, and 12 emission measurements starting 5 min post injection. For scatter correction (SC) we used a dual-window method adapted to 123I. Collimator blurring correction (CBC) was done by deconvolution in Fourier space and attenuation correction (AT) was applied on a preliminary (CBC) filtered back-projection reconstruction using 12 iterations of a preconditioned, regularized minimal residual algorithm. For each reconstruction, a calibration factor was derived from a uniform cylinder filled with a 123I solution of a known radioactivity concentration. Calibration and baboon images were systematically built with the same reconstruction parameters. Uncorrected (UNC) and (AT), (SC + AT) and (SC + CBC + AT) corrected images were compared. PET acquisitions using 0.11-0.44 GBq of 11C-epidepride were performed on the same baboons and used as a reference. The radioactive concentrations expressed in percent of the injected dose per 100 ml (% ID/100 ml) obtained after (SC + CBC + AT) in SPET are in good agreement with those obtained with PET and 11C-epidepride. A method for the in vivo absolute quantitation of 123I-epidepride uptake using SPET has been developed which can be directly applied to other 123I-labelled molecules used in the study of the dopamine system. Further work will consist in using PET to model the radioligand-receptor interactions and to derive a simplified model applicable in SPET.

Animals↗
PubMed1999

Effects of new criteria for type 2 diabetes on the rate of postpartum glucose intolerance in women with gestational diabetes.

OBJECTIVE: Our purpose was to determine the impact of the 1997 American Diabetes Association diagnostic criteria for type 2 diabetes mellitus on the rate of postpartum glucose intolerance in women with gestational diabetes. STUDY DESIGN: Women identified as having gestational diabetes were instructed to undergo a 75-g, 2-hour glucose tolerance test 4 to 6 weeks after delivery. The results were retrospectively categorized with both the 1979 National Diabetes Data Group criteria and those recommended by the American Diabetes Association in 1997. RESULTS: Though the rate of overt diabetes mellitus did not increase when the 1997 American Diabetes Association criteria were used (7.8% vs 5.6%, P = not significant), the rate of impaired glucose metabolism was higher (20.1% vs 5%, P <.001). Most women (28/30, 93%) with a nondiagnostic glucose tolerance test result by the older criteria had abnormal results by the newer criteria. Fifty women had abnormalities of glucose metabolism under 1997 American Diabetes Association criteria; 34% of these women had fasting plasma glucose values in the normal range. Of the 25 women with impaired glucose tolerance, 16 (64%) had only an abnormal 2-hour value, with normal fasting glucose values. CONCLUSIONS: The rate of postpartum abnormalities in glucose metabolism more than doubles when the 1997 American Diabetes Association criteria are applied; more women are identified with lesser degrees of impairment. However, relying on fasting glucose levels alone, without glucose tolerance testing, may miss one third of women with such abnormalities.

Blood Glucose↗
PubMed1999

Group B streptococcus infection rate unchanged by gestational diabetes.

OBJECTIVE: Group B streptococcal colonization in pregnancy has been associated with adverse perinatal outcomes, including intra-amniotic infection, postpartum endometritis, and neonatal sepsis. We sought to determine whether gestational diabetes increases the risk of maternal and neonatal morbidity from group B streptococcal colonization. METHODS: Gestational diabetic and nondiabetic women who underwent vaginal or anogenital culture for group B streptococcus colonization in pregnancy were followed up for pregnancy outcome. Antibiotic prophylaxis was not routinely given. Major perinatal morbidity included intraamniotic infection, endometritis, and neonatal sepsis. Potential confounding variables included induction of labor, cesarean delivery, prematurity, maternal antibiotic use, and prolonged rupture of membranes. RESULTS: We compared 446 gestational diabetic women to 1,046 nondiabetic women for outcome. Overall, 12% were colonized with group B streptococcus, with no difference in colonization rates between gestational diabetic (12%) and nondiabetic (12%) women. There were no differences in intraamniotic infection rates between gestational diabetic and nondiabetic women, whether group B streptococcus positive (16% compared with 13%) or group B streptococcus negative (10% compared with 11%). Likewise, endometritis did not differ (6-9%) regardless of diabetes or group B streptococcus status. Neonatal sepsis was higher in group B streptococcus-positive women overall (3% compared with 1%, odds ratio 3.71, 95% confidence interval 1.23, 10.81), but did not differ between diabetic and nondiabetic pregnancies. CONCLUSION: Gestational diabetes does not alter the perinatal morbidity associated with group B streptococcal colonization in pregnancy.

Adult↗
PubMed1999

Dietary therapy for gestational diabetes: how long is long enough?

OBJECTIVE: To determine the length of time required for dietary therapy alone to effect good glycemic control and whether the need for insulin treatment can be predicted at diagnosis of gestational diabetes mellitus (GDM). METHODS: Women with GDM were treated with dietary therapy for 4 weeks. Each measured her blood glucose using a memory-based reflectance glucometer, and those in poor glycemic control (mean glucose exceeding 105 mg/dL) after 4 weeks of dietary therapy were prescribed insulin. Women were stratified by fasting plasma glucose value of 3-hour glucose tolerance tests (GTTs). RESULTS: Women with fasting glucose at or below 95 mg/dL were significantly more likely to achieve good glycemic control after 2 weeks of dietary therapy than were those with values above 95 mg/dL whose control did not improve during the study. Receiver operating characteristic (ROC) analysis determined that fasting values of GTT between 91 and 95 mg/dL best predicted that insulin would be needed for good glycemic control. CONCLUSION: Women with GDM should be prescribed dietary therapy alone for at least 2 weeks before they are prescribed insulin. In those with fasting glucose above 95 mg/dL, insulin may be prescribed after 1 week of dietary therapy, or at diagnosis.

Adult↗
PubMed1999

Carbon-11 epidepride: a suitable radioligand for PET investigation of striatal and extrastriatal dopamine D2 receptors.

Epidepride [(S)-(-)-N-([1-ethyl-2-pyrrolidinyl]methyl)-5-iodo-2,3-dimethoxybenza mide] binds with a picomolar affinity (Ki = 24 pM) to the dopamine D2 receptor. Iodine-123-labeled epidepride has been used previously to study striatal and extrastriatal dopamine D2 receptors with single photon emission computed tomography (SPECT). Our aim was to label epidepride with carbon-11 for comparative quantitative studies between positron emission tomography (PET) and SPECT. Epidepride was synthesized from its bromo-analogue FLB 457 via the corresponding trimethyl-tin derivative. In an alternative synthetic pathway, the corresponding substituted benzoic acid was reacted with the optically pure aminomethylpyrrolidine-derivative. Demethylation of epidepride gave the desmethyl-derivative, which was reacted with [11C]methyl triflate. Total radiochemical yield was 40-50% within a total synthesis time of 30 min. The specific radioactivity at the end of synthesis was 37-111 GBq/micromol (1,000-3,000 Ci/mmol). Human postmortem whole-hemisphere autoradiography demonstrated dense binding in the caudate putamen, and also in extrastriatal areas such as the thalamus and the neocortex. The binding was inhibited by unlabeled raclopride. PET studies in a cynomolgus monkey demonstrated high uptake in the striatum and in several extrastriatal regions. At 90 min after injection, uptake in the striatum, thalamus and neocortex was about 11, 4, and 2 times higher than in the cerebellum, respectively. Pretreatment experiment with unlabeled raclopride (1 mg/kg) inhibited 50-70% of [11C]epidepride binding. The fraction of unchanged [11C]epidepride in monkey plasma determined by a gradient high performance liquid chromatography (HPLC) method was about 30% of the total radioactivity at 30 min after injection of [11C]epidepride. The availability of [11C]epidepride allows the PET-verification of the data obtained from quantitation studies with SPECT.

Autoradiography↗
PubMed1999

The large fetus.

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Cesarean Section↗
PubMed1999

Electronic fetal monitoring: what's reassuring?

BACKGROUND: To determine which combinations of fetal heart rate pattern abnormalities are associated with normal outcome in term pregnancies. METHODS: A cohort of 2200 consecutive deliveries was examined and the fetal heart rate tracings analyzed. Singleton, term patients without chorioamnionitis or serious malformations were used to perform logistic regression analysis to select those FHR patterns associated with increased risk for Apgar<7 and cord pH<7.15, or immediate adverse outcome. RESULTS: Patients having no fetal heart rate abnormalities, mild variable decelerations, decreased variability, mild bradycardia, or accelerations present, constituted 84% of all fetal heart rate tracings. These tracings alone, or in combination, predicted 5 minute Apgar score> or =7 in 99.7%, cord pH> or =7.15 in 96.9% and no adverse neonatal sequelae in 96.2% of cases. Accelerations were reassuring regardless of FHR pattern. When these patterns were not present, non-reassuring tracings, the risk for immediate adverse outcome increased 50%. The non-reassuring tracings were both without accelerations and had tachycardia, prolonged bradycardia, severe variable or late decelerations, or a combination of these patterns. This increased risk was independent of the risk of confounders: i.e. thick meconium (1.8-fold), prolonged second stage of labor (>50 min., 1.5-fold), maternal disease (e.g. kidney, respiratory, 3-fold), or hypertensive disease (1.9-fold). CONCLUSIONS: The great majority of fetal heart rate pattern abnormalities can be considered reassuring as they are within normal variations of a healthy fetus. The non-reassuring ones identify infants that truly require further evaluation by fetal scalp, vibroacoustic stimulation, or fetal scalp blood sampling.

Bradycardia↗
PubMed1998

Elective delivery of infants with macrosomia in diabetic women: reduced shoulder dystocia versus increased cesarean deliveries.

OBJECTIVE: We sought to test the hypothesis that elective delivery of infants diagnosed with macrosomia by ultrasonographic studies in diabetic women will significantly reduce the rate of shoulder dystocia without significantly increasing cesarean section rate. STUDY DESIGN: In a prospective study diabetic women with ultrasonographic estimated fetal weight > or = 4250 gm underwent elective cesarean section; women with estimated fetal weight > or = 90th percentile but < 4250 gm underwent induction of labor. Maternal and neonatal outcomes were analyzed and compared for the periods before and after initiation of the protocol. RESULTS: A total of 2604 diabetic patients were included in this study. The rate of shoulder dystocia was significantly lower after instituting the protocol (2.4% vs 1.1%, odds ratio 2.2). The cesarean section rate increased significantly between the two periods (21.7% vs 25.1%, p < 0.04). Ultrasonography correctly identified the presence or absence of macrosomia in 87% of patients. Only 10.6% of diabetic patients at term required intervention under the protocol (6.8% labor induction, 3.8% elective cesarean section). The rate of shoulder dystocia was 7.4% in macrosomic infants delivered vaginally. CONCLUSION: An ultrasonographically estimated weight threshold as an indication for elective delivery in diabetic women reduces the rate of shoulder dystocia without a clinically meaningful increase in cesarean section rate. This practice, in conjunction with an intensified management approach to diabetes, improves the outcome of these high-risk women and their infants.

Adult↗
PubMed1998

Maternal glycemic criteria for insulin therapy in gestational diabetes mellitus.

In the last decade, it has become clear that gestational diabetes is a clinical entity associated with perinatal mortality and morbidity. Thus, the attention to and management of gestational diabetes during pregnancy are mandatory. In this review, results of 58 original studies (spanning the past 20 years) addressing criteria for insulin management in gestational diabetes were assessed. The level of glycemic control and its evaluation through self-monitoring of blood glucose are the foundation for ascertaining optimal pregnancy outcome. This review addresses the criteria for insulin initiation: insulin requirements, identification of the right patient, the timing for insulin initiation, and the behavioral adjustment and compliance during insulin therapy. It is recommended that patients with fasting plasma glucose on the oral glucose tolerance test (OGTT) of < 96 mg/dl (and ideally nonobese) be assigned to diet therapy. Obese women or those with fasting plasma glucose > 95 mg/dl on the OGTT should be referred to insulin therapy in order to minimize exposure of the fetus to a hyperglycemic environment.

Blood Glucose↗
PubMed1997

Human placental glucose uptake and transport are not altered by the oral antihyperglycemic agent metformin.

OBJECTIVE: Our purpose was to determine whether the biguanide oral antihyperglycemic agent metformin increases human placental uptake and transport of glucose to the fetal circulation. STUDY DESIGN: The human single-cotyledon model was used to compare transport of tritiated glucose in the maternal to fetal direction in eight human placentas between control placentas and those exposed to metformin in vitro. Transport was calculated from the serial perfusate glucose levels obtained in each 3-hour experiment, and placental uptake was determined from homogenates of the perfused cotyledon. Liquid scintillation spectrometry measured levels of both glucose and the reference substance antipyrine. Transport was compared by the Mann-Whitney U test. RESULTS: Mean maternal and fetal glucose levels were 77.5 +/- 4.9 mg/dl and 61.3 +/- 5.9 mg/dl, respectively, in the metformin group and 83.8 +/- 4.3 mg/dl and 60.4 +/- 12.4 mg/dl, respectively, in controls at 2 hours. Placental glucose uptake was 91.1 +/- 42.2 microg/gm placenta in the metformin experiments and 104.9 +/- 76.9 microg/gm placenta in controls. No difference in placental glucose uptake or transport could be demonstrated. CONCLUSION: Metformin does not affect human placental glucose uptake or transport.

Blood Glucose↗
PubMed1997

Preeclampsia: is induction of labor more successful?

OBJECTIVE: To test the hypothesis that preeclamptic women are more readily inducible than are nonpreeclamptic women, regardless of cervical condition. METHODS: One hundred eighty-three preeclamptic women and 461 nonpreeclamptic women requiring labor induction were studied prospectively. Patients were categorized by Bishop score, parity, gestational age, and method of induction. Outcome variables were success of induction and cesarean delivery rates. RESULTS: Failed induction was significantly more common in the preeclamptic group (8.2% versus 1.7%; odds ratio [OR] 5.06; 95% confidence interval [CI] 1.97, 13.28), as was cesarean delivery (28% versus 16%; OR 2.09; 95% CI 1.36, 3.18). When controlled by logistic regression for Bishop score, parity, method of induction, epidural anesthesia, macrosomia, and gestational age, a fourfold higher risk of failed induction and a twofold higher risk of cesarean delivery were found in the preeclamptic group. CONCLUSIONS: Induction of labor in preeclamptic women has a higher risk of failure and consequently of cesarean delivery than in nonpreeclamptic women. The vast majority of patients achieve vaginal delivery.

Adult↗
PubMed1997

Induction of labor in the nineties: conquering the unfavorable cervix.

OBJECTIVE: To determine the efficacy, safety, and duration of induced labor using an integrative approach (prostaglandin, amniotomy, oxytocin) and to depict these findings graphically. METHODS: Five hundred ninety-seven pregnancies requiring induction of labor between October 1993 and May 1995 were analyzed prospectively. Patients were categorized by Bishop score at entry and by parity for comparison of success of induction, maternal and fetal complications, and duration of labor. RESULTS: The women who had a Bishop score at entry of 3 or less had significantly higher rates of failed induction (9.4 versus 0.7%, P < .01) and of cesarean delivery (29 versus 15.4%, P < .01) than those with a Bishop score above 3. Compared with spontaneous labor, the rates of cesarean delivery in induced labor remained significantly elevated. Complications of induction were infrequent, regardless of Bishop score. The time from initiation of induction to achievement of active phase was significantly longer in women with lower Bishop scores. CONCLUSION: Regardless of cervical status and parity, vaginal delivery can be anticipated in the majority of patients undergoing labor induction. The induction characteristics described may assist in the management of induced labor.

Adult↗
PubMed1996

Do growth-retarded premature infants have different rates of perinatal morbidity and mortality than appropriately grown premature infants?

OBJECTIVE: To determine if perinatal morbidity and mortality differ in growth-retarded, small for gestational age (SGA), premature infants and appropriate for gestational age (AGA) infants. METHODS: All consecutive, singleton, nondiabetic, preterm pregnancies delivered over a 15-year period were analyzed. Infants were categorized as SGA (at or below the tenth percentile) or AGA (11th to the 89th percentiles), then stratified by birth weight and gestational age categories. Perinatal morbidity and mortality were examined. RESULTS: We studied 4183 preterm deliveries, 1012 of them SGA and 3171 of them AGA. Overall, we found significantly higher rates of fetal and neonatal death in the SGA group. Stratification by gestational age revealed significantly higher rates of neonatal death for the SGA group compared with the AGA group in each gestational age category. Overall, comparison also revealed significantly higher rates of fetal heart rate abnormality in the SGA group but no difference in neonatal sepsis, birth trauma, cesarean delivery, hyaline membrane disease, or congenital anomalies. CONCLUSION: Growth-retarded premature infants have a significantly higher risk of morbidity and mortality, both before and after delivery, than do appropriately grown infants.

Confidence Intervals↗
PubMed1996

Perinatal outcome in growth-restricted fetuses: do hypertensive and normotensive pregnancies differ?

OBJECTIVE: To test the hypothesis that fetal growth restriction (FGR) associated with a maternal hypertensive disorder results in worse perinatal outcome than FGR in pregnancies without maternal hypertension. METHODS: All consecutive, singleton, nondiabetic, small for gestational age (SGA) deliveries (birth weight at or below the tenth percentile for gestational age) in a 15-year computerized data base were analyzed for pregnancy outcome. Perinatal outcome was compared after stratification by presence or absence of hypertensive disorders and by gestational age at delivery. RESULTS: Eleven thousand two hundred twenty-seven SGA pregnancies were analyzed. The morbidity and mortality profiles differed between hypertensive and normotensive pregnancies delivered preterm and those delivered at term. Perinatal mortality was significantly higher in the normotensive than in the hypertensive group in preterm deliveries (30.3 versus 18.7%, odds ratio [OR] 1.9 [confidence interval (CI) 1.3-2.9]). At term, hypertensive pregnancies demonstrated significantly higher mortality than normotensive pregnancies (4.6 versus 1.9%, OR 2.42 [95% CI 1.7-3.4]). In both preterm and term gestations, cesarean rates were significantly higher in hypertensive pregnancies than in normotensive pregnancies. Using logistic regression analysis, hypertension was independently associated with a 39% reduction in risk of perinatal mortality preterm, compared with a twofold increased risk of perinatal mortality at term. CONCLUSION: Before term, FGR in normotensive women resulted in significantly higher perinatal mortality than FGR in hypertensive women. In contrast, at term, FGR in pregnancies complicated by hypertension had poorer perinatal outcomes than FGR in normotensive women.

Adult↗