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Biomedical subjects

S G Gabbe

Publications and source records attributed to S G Gabbe.

At least 37 records · Page 2Linked to original sources

Fetal surveillance and timing of delivery in pregnancy complicated by diabetes mellitus.

Protocols for antepartum fetal assessment in pregnancies complicated by diabetes mellitus are an important part of a care program that allows most of these pregnancies to reach term, ensuring fetal maturation. Maternal assessment of fetal activity serves as an efficient screening test in most surveillance programs. These programs have used primarily biophysical testing consisting of the nonstress test, cardiac stress test, or biophysical profile. Doppler studies have been investigated as an adjunct for identifying fetal compromise. These studies may prove most valuable in cases of maternal vascular disease. The success of these protocols continues to be predicated on careful regulation of maternal glycemia through aggressive therapy with insulin and diet. Reassuring tests of fetal condition are present in most diabetic women and, therefore, permit fetal maturation to occur prior to delivery.

Blood Glucose↗

Coronary artery disease in insulin-dependent diabetes mellitus of pregnancy (class H): a review of the literature.

Coronary heart disease and myocardial infarction are uncommon complications during pregnancy. Women with insulin-dependent diabetes mellitus (IDDM) have a much greater risk of serious coronary heart disease, but few cases of myocardial infarctions occurring during pregnancy have been reported. Significant maternal morbidity has been reported in half of these cases. This is a case of a myocardial infarction occurring at 21 weeks of gestation in a patient with class R/F IDDM and the subsequent pregnancy management as well as a review of the literature concerning Class H IDDM in pregnancy.

Adult↗

Pregnancy in diabetes: reducing the risks.

Meticulous glucose control that begins long before conception is fundamental to protecting the fetus and mother. Maternal hypertension, retinopathy, renal disease, and neuropathy may lead to complications, but optimal education, care, and fetal monitoring can reduce the risks.

Adult↗

Gestational diabetes survey.

OBJECTIVE: Our purpose was to determine how residents in obstetrics and gynecology and fellows in maternal-fetal medicine are currently being trained to diagnose and manage gestational diabetes mellitus. STUDY DESIGN: Questionnaires were mailed to 202 obstetrics and gynecology residency program directors and 78 maternal-fetal medicine fellowship directors. RESULTS: Sixty-four (82%) of the maternal-fetal medicine directors versus 142 (70%) of the residency directors responded. Universal screening, use of a 50 gm glucose challenge with a 1-hour-postingestion sample, no requirements for fasting before the screening test, use of two abnormal values on the 3-hour glucose tolerance test to define gestational diabetes mellitus, and initiation of insulin for elevated fasting glucose levels in spite of diet therapy were each recommended by > 90% of the respondents. CONCLUSION: Although the optimal management of gestational diabetes mellitus remains controversial, program directors are in general agreement with many aspects of the diagnosis and management.

Data Collection↗

Insulin and glucose modulate glucose transporter messenger ribonucleic acid expression and glucose uptake in trophoblasts isolated from first-trimester chorionic villi.

OBJECTIVE: Our purpose was to determine the effects of insulin and glucose on glucose transport and expression of GLUT1 glucose transporter messenger ribonucleic acid in first-trimester human trophoblast-like cells. STUDY DESIGN: First-trimester human trophoblast-like cells were maintained as a continuous cell line. For 2[3H]deoxy-D-glucose uptake and messenger ribonucleic acid studies the cells were incubated in the presence or absence of insulin (10(-7) to 10(-11) mol/L) or D-glucose (0 to 50 mmol/L) for 0 to 24 hours. Glucose transport was measured by incubating cells with 0.1 mmol/L 2[3H]deoxy-D-glucose for 5 minutes. Specific uptake was determined by incubating companion cultures with 10 mumol/L cytochalasin B. The cells were then solubilized with sodium hydroxide and the radioactivity counted. Data were expressed as nanomoles of 2[3H]deoxy-D-glucose transported per milligram of protein per 5 minutes and analyzed by one-way analysis of variance with post hoc testing by the method of Tukey. GLUT1 messenger ribonucleic acid was measured by Northern blotting of total ribonucleic acid samples hybridized to a phosphorus 32-labeled complementary deoxyribonucleic encoding the rat GLUT1 glucose transporter. As a control for loading efficiency, blots were stripped and rehybridized to a 40-mer phosphorus 32-labeled beta-actin oligonucleotide probe. RESULTS: Insulin treatment resulted in a dose-dependent increase in the transport of 2[3H]deoxy-D-glucose at 24 hours (p < 0.001 at 10(-7) mol/L). This change was first detected at 12 hours of incubation. These data closely paralleled the insulin-induced increase in GLUT1 messenger ribonucleic acid seen in Northern blots. In contrast to insulin, increasing concentrations of D-glucose did not change the transport of 2[3H]deoxy-D-glucose. However, when cells were incubated in low concentrations of D-glucose (0 or 1 mmol/L), an enhancement in the uptake of 2[3H]deoxy-D-glucose (p < 0.001) was observed. Kinetic studies indicated that D-glucose augmentation of 2[3H]eoxy-D-glucose uptake was significant at 9 hours (p < 0.05). The effects of D-glucose on GLUT1 messenger ribonucleic acid expression paralleled the uptake of 2[3H]deoxy-D-glucose, although the modulation of GLUT1 messenger ribonucleic acid levels by glucose was much less pronounced than in insulin-treated cells. CONCLUSION: Although it has been assumed that the placenta has a limited role in influencing glucose transport to the fetus, our in vitro data demonstrate that both insulin and glucose can modulate glucose transport at the cellular level of the placental trophoblast. Thus maternal insulin and glycemic status may influence the expression of GLUT1, the major trophoblast glucose transporter protein, therefore directly affecting first-trimester placental glucose transport. These in vitro data may help explain the association between maternal glucose abnormalities and impaired fetal development during the first trimester when placental GLUT1 messenger ribonucleic acid expression is at its peak.

Analysis of Variance↗

Ease and accuracy of evaluation of fetal hands during obstetrical ultrasonography: a prospective study.

Hand malformations characterize many congenital syndromes, including mendelian disorders, skeletal dysplasias, and karyotype abnormalities. Although identification of a hand anomaly alters obstetrical management, evaluation of the fetal hands is not included in current ultrasonographic guidelines. We prospectively studied the utility of allotting up to 5 min to examine fetal hands during obstetrical ultrasonography. Both hands were visualized in 87% of patients (188 of 215). Eight hand abnormalities were present at delivery. Six had been identified antenatally, four during the study with ultrasonography. There were no false positives. Four fetuses with hand malformations were aneuploid. Fetal hands should be examined during a comprehensive obstetrical sonographic evaluation, especially when risk factors for aneuploidy are present.

Aneuploidy↗

The differential effects of body fat distribution on insulin and glucose metabolism during pregnancy.

OBJECTIVE: Our purpose was to investigate whether maternal obesity, or more specifically body fat distribution, is associated with alterations in carbohydrate metabolism during pregnancy. STUDY DESIGN: A longitudinal study of oral glucose tolerance tests, insulin, C peptide, and glucagon levels during each trimester and post partum was undertaken in nine lean and 14 obese women. Obese women were divided into lower body obese (n = 6, waist/hip ratio < 0.9) and upper body obese (n = 8, waist/hip ratio > or = 0.9). RESULTS: Fasting blood glucose levels declined with advancing gestation only in lean subjects. Upper body obese women demonstrated maximal glucose response and insulin area under the curve by the second trimester, whereas lean and lower body obese women did not until the third trimester. Insulin areas were significantly elevated in upper body obese compared with lower body obese women (second trimester, p < 0.01; third trimester, p < 0.03; post partum p < 0.05). In contrast, C peptide levels were similar in obese subgroups and were significantly elevated only when compared with those of lean women. C peptide/insulin molar ratios were lower in upper body obese women during the second trimester (4.3 +/- 0.8) and third trimester (4.2 +/- 0.7) compared with lean (6.5 +/- 1.3, 6.7 +/- 0.5) and lower body obese women (7.9 +/- 1.4, 6.5 +/- 1.4) (p < 0.01). A significant relationship between waist/hip ratio and glucose level (r = 0.70, p < 0.004) and insulin areas (r = 0.76, p < 0.001) was present in late pregnancy in obese subjects. CONCLUSIONS: Relative hyperinsulinemia and earlier maximal glucose response in upper body obese women suggests that body fat distribution may explain the metabolic heterogeneity present in obese women during pregnancy. Body fat topography may serve as a potential marker for the early development of carbohydrate intolerance during pregnancy.

Adipose Tissue↗

Insulinlike growth factors. Their regulation of glucose and amino acid transport in placental trophoblasts isolated from first-trimester chorionic villi.

The transport of glucose and amino acids from the maternal to fetal circulation through the placenta is critical to the delivery of fuel for normal fetal growth and development. Little information indicates that transplacental glucose or amino acid transport is influenced by hormones or polypeptide growth factors. We developed a continuous cell line of cytotrophoblastlike cells derived from first-trimester human chorionic villi as a model system to study the regulation of glucose and amino acid transport by insulinlike growth factors (IGFs). Using immunocytochemical and biochemical criteria, the cells were shown to manifest a trophoblastlike phenotype. The cells were maintained in serum-supplemented medium until confluent, at which time they were shifted to serum-free medium for one day. Experiments were initiated by transferring the cells to glucose-free assay buffer and incubating them with IGF-I, IGF-II or insulin. Glucose uptake was measured by the transport of 2-deoxy-D-[1,2-3H]glucose (2[3H]DG) in the presence or absence of cytochalasin B, which has been shown to competitively inhibit glucose uptake. IGF-I, IGF-II and insulin each enhanced 2[3H]DG transport in a dose-dependent fashion. Amino acid transport was measured by incubation of the cells with IGF-I for 60 minutes, followed by a 5-minute challenge with alpha-[methyl-3H]aminoisobutyric acid. IGF-I caused a dose-dependent increase in uptake of the amino acid analog. Radioreceptor assays using [125I]insulinlike growth factor I ([125I]IGF-I) demonstrated that the trophoblast-derived cells contained high-affinity, saturable receptors for IGF-I that also bound IGF-II.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Expression of functional insulin-like growth factor-I receptors by human amnion cells.

OBJECTIVES: The purpose of the study was to investigate whether amnion cells contain functional insulin-like growth factor-I receptors. STUDY DESIGN: To test whether human amnion cells contain insulin-like growth factor-I receptors, radioligand binding studies, affinity cross-linking studies, and Northern blot analysis were conducted in primary amnion cells and in an immortal amnion cell line (WISH). To test whether the insulin-like growth factor-I receptors on amnion cells are functional, cytochalasin B-inhibitable 2-deoxyglucose uptake was measured after stimulating the cells with insulin-like growth factor-I. RESULTS: Radioligand binding studies demonstrated that primary amnion cells and WISH cells contained a single class of high-affinity receptors with an apparent dissociation constant of 0.18 +/- 0.04 nmol/L and a receptor concentration of 79 +/- 26.2 fmol/mg protein and dissociation constant of 0.44 +/- 0.03 nmol/L and a receptor concentration of 33.3 +/- 6.45 fmol per 106 cells, respectively. Affinity cross-linking studies revealed two major insulin-like growth factor-I binding sites, 135 and 270 kd. Both primary amnion cells and WISH cells exhibited cytochalasin B-inhibitable tritiated 2-deoxyglucose uptake in response to insulin-like growth factor-I treatment. Finally, treatment of WISH cells caused tyrosine phosphorylation of three proteins (molecular weight, 116, 95.4, and 83.5 kd) was observed by Western blotting with antiphosphotyrosine antibodies. CONCLUSION: These results provide the first evidence that human amnion epithelial cells contain functional high-affinity insulin-like growth factor-I receptors that mediate glucose transport.

Amnion↗

Effect of prolonged oral terbutaline therapy on glucose tolerance in pregnancy.

OBJECTIVE: Our objective was to elucidate the pathophysiologic effects and potential reversibility of terbutaline-induced changes in carbohydrate metabolism. STUDY DESIGN: We prospectively evaluated serum glucose, insulin, glucagon, C-peptide, and pancreatic polypeptide levels in response to a 100 gm glucose challenge (oral 3-hour glucose tolerance test) in 17 obstetric patients without complications who were given terbutaline (5 mg orally every 4 hours) for 5 consecutive days between 24 and 32 weeks' gestation. Each patient served as her own control, with day 1 representing pretreatment, day 7 the treatment phase, and day 14 the posttreatment evaluation. Body mass index and posttreatment serum terbutaline levels were also measured. RESULTS: A significant initial treatment effect (day 1 versus 7) was observed for glucose (elevated), insulin (elevated), insulin/glucose ratio (elevated), and pancreatic polypeptide (elevated). A significant delayed treatment effect (day 1 versus 14) was also observed for insulin (elevated), insulin/glucose ratio (elevated), and pancreatic polypeptide (elevated). Body mass index directly correlated with postchallenge measures of insulin, insulin/glucose ratio, pancreatic polypeptide, and C-peptide. Posttreatment serum terbutaline levels directly correlated with pancreatic polypeptide, but not with other parameters. CONCLUSIONS: Our data support a dose-independent, terbutaline-induced glucose intolerance mediated by glucagon and caused by diminished insulin sensitivity.

Administration, Oral↗

Three cases of Haemophilus influenzae amnionitis.

Haemophilus influenzae is an uncommon cause of obstetric and neonatal infections. Three cases of amnionitis caused by H. influenzae are presented. These cases occurred in three maternal transports to our tertiary level hospital within an 11-day period. The organisms were analyzed for biotypes, penicillinase status, and composition of membrane fatty acids.

Adolescent↗

Doppler ultrasonography of the umbilical cord in normal pregnancy.

Using continuous wave Doppler ultrasonography to measure umbilical artery flow velocity waveforms (FVWs) is a safe, noninvasive means of quantifying placental resistance to blood flow. Detection of abnormally elevated resistance to umbilical perfusion may identify pregnancies complicated by uteroplacental insufficiency. Use of this technique to identify high-risk pregnancies requires ready access to standard tables of normal FVW values obtained from well-defined populations under usual clinical conditions. We report measurements of the systolic-diastolic (S-D) ratio of the umbilical artery obtained between 16 and 43 weeks in 122 normal pregnancies. A gestational-age-adjusted table of normal values is presented.

Adolescent↗

Cost-benefit analysis of preconception care for women with established diabetes mellitus.

OBJECTIVE: To determine whether the additional costs of preconception care are balanced by the savings from averted complications. Several studies have demonstrated the efficacy of preconception care in reducing congenital anomalies in infants born of mothers with pre-existing diabetes mellitus. RESEARCH DESIGN AND METHODS: This study used literature review, consensus development among an expert panel of physicians, and surveys of medical care personnel to obtain information about the costs and consequences of preconception plus prenatal care compared with prenatal care only for women with established diabetes. Preconception care involves close interaction between the patient and an interdisciplinary health-care team as well as intensified evaluation, follow-up, testing, and monitoring. The outcome measures assessed in this study are the medical costs of preconception care versus prenatal care only and the benefit-cost ratio. RESULTS: The costs of preconception plus prenatal care are $17,519/delivery, whereas the costs of prenatal care only are $13,843/delivery. Taking into account maternal and neonatal adverse outcomes, the net savings of preconception care are $1720/enrollee over prenatal care only and the benefit-cost ratio is 1.86. The preconception care program remained cost saving across a wide range of assumptions regarding incidence of adverse outcomes and program cost components. CONCLUSIONS: Despite significantly higher per delivery costs for participants in a hypothetical preconception care program, intensive medical care before conception resulted in cost savings compared with prenatal care only. Third-party payers can expect to realize cost savings by reimbursing preconception care in this high-risk population.

Blood Glucose↗

Pregnancy in women with diabetes mellitus. The beginning.

Before the discovery of insulin in 1921, pregnancies in women with diabetes mellitus were uncommon. Most patients succumbed to ketoacidosis within 1 to 2 years after diagnosis. Insulin therapy restored the fertility of these women, and maternal deaths were nearly eliminated; however, the perinatal mortality rate remained high. Elective preterm deliveries were planned to reduce the stillbirth rate, often resulting in neonatal deaths from respiratory distress syndrome. Furthermore, women with more severe disease were able to become pregnant with a risk of complications due to preeclampsia.

Diabetes Mellitus, Type 1↗

Fetal surveillance in the pregnancy complicated by diabetes mellitus.

During the last 15 years, protocols for antepartum fetal assessment in pregnancies complicated by diabetes mellitus have shifted the focus of care during the third trimester to an outpatient setting, reducing health care costs and emotional stress on patients and their families. Maternal assessment of fetal activity is the primary screening test in most surveillance programs, which use the nonstress test, contraction stress test, or biophysical profile. The success of these protocols continues to be predicted on careful regulation of maternal glycemia through aggressive therapy with insulin and diet.

Delivery, Obstetric↗

Fetal surveillance in pregnancies complicated by insulin-dependent diabetes mellitus.

OBJECTIVE: Our objective was to determine whether maternal vascular disease and/or glycemic control can be related to tests of fetal condition in diabetic pregnancies. STUDY DESIGN: A total of 114 women with insulin-dependent diabetes who used a memory-based glucose reflectance meter were prospectively evaluated. Nonstress testing was begun weekly at 28 to 30 weeks and twice weekly at 32 weeks. A nonreactive nonstress test was followed by a biophysical profile in all cases. RESULTS: A total of 1676 nonstress tests was performed (14.7 +/- 3.2 tests per patient). Eight percent (n = 134) were nonreactive, necessitating a biophysical profile. A comparison of ambulatory glucose profile data, including mean blood glucose level, variation, and excursions from the median, revealed no significant differences in patients with reactive versus nonreactive nonstress tests. Ten patients, including eight with vascular disease, were delivered because of abnormal test results of fetal condition. Nephropathy or hypertension was associated with intervention for fetal well-being in 8 of 20 women (40%) with these risk factors. Only 2 of 94 patients (2%) without nephropathy or hypertension required delivery because of abnormal results of fetal testing (p less than 0.001). One fetal death occurred. No significant differences in the various glycemic parameters were found in women delivered for suspected fetal jeopardy versus the nonintervention group. CONCLUSION: Pregnancies complicated by vascular disease are at greatest risk for abnormal results of fetal testing that necessitate early delivery. Women without vascular complications and with maintenance of good glycemic control rarely have fetal compromise.

Delivery, Obstetric↗

Study of thromboxane and prostacyclin metabolism in an in vitro model of first-trimester human trophoblast.

OBJECTIVES: The purpose of our study was to establish an in vitro tissue culture system to study eicosanoid metabolism in first-trimester trophoblastic tissue. Thromboxane A2, a potent vasoconstrictor, and prostacyclin, a potent vasodilator, were analyzed to evaluate their production in early pregnancy. STUDY DESIGN: Trophoblastic tissue was obtained via transabdominal chorionic villous sampling from 33 pregnancies at 9 to 12 weeks' gestation for cytogenetic diagnosis. Initially, tissue obtained from the cytogenetics lab was morphologically consistent with villous core cells. Through altering cell density and passage, the cells became morphologically consistent with cytotrophoblasts. The cell lines were exposed to arachidonic acid (50 mumol/L) and aspirin (1 to 100 mumol/L) for 24 hours. Thromboxane B2 and 6-keto prostaglandin F2 alpha were measured by radioimmunoassay. RESULTS: Villous core cells and cytotrophoblasts increased production of thromboxane A2 and prostacyclin in the presence of arachidonic acid (p < 0.002). The villous core cells produced more thromboxane A2 and prostacyclin than cytotrophoblasts (p < 0.02). A significant inhibition of both thromboxane A2 and prostacyclin production was seen in the presence of 100 mumol/L aspirin in both cell types (p < 0.05). CONCLUSIONS: This model may be useful for studying placental function in the first trimester because individual placental compartments can be evaluated in tissue culture. At the cellular level we were not able to detect a preferential decrease in thromboxane A2 production in the presence of aspirin (1 to 100 mumol/L).

6-Ketoprostaglandin F1 alpha↗