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Biomedical subjects

M B Landon

Publications and source records attributed to M B Landon.

At least 37 records · Page 2Linked to original sources

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↗

Prevention of neonatal group B streptococcal infection.

The optimal clinical strategy to prevent neonatal group B streptococcal infection has not been established. The Maternal-Fetal Medicine Units Network assessed the feasibility of a randomized clinical trial to compare the effectiveness of two methods of prevention of streptococcal infection. The attack rates of early-onset group B streptococcal disease were estimated for the following: 1) a hypothetical program of universal prenatal screening and selective intrapartum chemoprophylaxis, and 2) a hypothetical program of selective intrapartum chemoprophylaxis based on clinical risk factors. Sample size requirements were calculated for a clinical trial to detect a significant difference in attack rates between the two hypothetical programs. Similar low attack rates using both strategies would require extremely large sample sizes to detect differences between programs. Until a satisfactory, rapid diagnostic test for intrapartum group B streptococcal carrier status is developed and clinical strategies are tested in populations with varying carriage frequencies, institutions will need to individualize their approaches to prevent early-onset neonatal group B streptococcal disease.

Algorithms↗

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↗

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↗

Infant of the diabetic mother.

Despite marked declines in neonatal mortality, infants of diabetic mothers still experience significant morbidity. This article reviews current data regarding congenital malformations, disorders of fetal growth, pulmonary development, and diagnosis and treatment of hypoglycemia, hypocalcemia, and hypomagnesemia. It also addresses short-term and long-term complications for this unique group of high-risk infants.

Congenital Abnormalities↗

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↗

Perinatal outcome for women in prison.

Pregnancy outcome for 233 women in prison was reviewed. This group of patients presented with multiple perinatal high-risk factors: history of illicit drug use (71%), smoking (70%), and obstetrical (27%), medical (21%), nutritional (20%), and infectious complications (20%). Maternal morbidity was uncommon and the overall cesarean section rate for all prisoners was 16%. There was 1 stillbirth and 236 live-born infants, all of whom were discharged in good health. Prematurity (3%) and delivery of small-for-gestational-age (SGA) (8%) infants was less common among 187 women who received adequate prenatal care than in 46 prisoners with poor or late prenatal care (prematurity 20% and SGA 28%). Good perinatal outcome for women in prison can be achieved if comprehensive prenatal care is available.

Adult↗

Diabetes mellitus and pregnancy.

Diabetes mellitus represents the most common medical complication of pregnancy. Care programs emphasizing normalization of maternal glucose levels have resulted in perinatal outcome that is nearly equivalent to that observed in normal pregnancies. Reducing the rate of significant congenital anomalies in insulin-dependent women remains a goal for the future.

Diabetes, Gestational↗

Sonographic measurement of fetal humeral soft tissue thickness in pregnancy complicated by GDM.

Sonographic measurement of fetal humeral soft tissue thickness (STT) was performed in 93 women with gestational diabetes mellitus during the third trimester. STT measurements revealed accelerated growth in large for gestational age infants at 31 wk gestation. This new measurement proved to be the most accurate predictor of excessive fetal size compared with other standard ultrasound parameters (sensitivity 82%, specificity 95%, positive predictive value 90%). Asymmetrical growth was more evident in infants with large STT measurements in utero. Humeral STT measurement may distinguish large fetuses with truncal obesity from those that are symmetrically large, thereby allowing prediction of risk for birth trauma before delivery.

Diabetes, Gestational↗

Duration of incarceration and perinatal outcome.

The number of incarcerated women is increasing, thus pregnancy in prison is no longer uncommon. We reviewed the perinatal outcome of 53 women with short-term incarceration (fewer than 90 days) and of 53 women who experienced long-term incarceration (more than 120 days). Poor prenatal care, history of drug abuse, hepatitis, and poor nutrition were more common among the short-incarceration group. Of infants born to short-incarceration women, 32 (60%) were normal, four (7%) stillborn, eight (15%) premature, six (11%) small for gestational age, and four (7%) septic. Women in the long-incarceration group delivered 48 normal infants (91%), whereas two were offspring of diabetic mothers and three were premature. Birth weight for infants born to smokers in the short-incarceration group was significantly lower than that of infants born to smokers in the long-incarceration group. Women who suffer short incarcerations experience high perinatal mortality and morbidity. In contrast, those incarcerated longer appear to benefit from better prenatal care, improved nutrition, and a structured environment, and thus a more favorable perinatal outcome.

Adult↗

Fetal surveillance in the pregnancy complicated by diabetes mellitus.

During the last decade, outpatient protocols have been developed for antepartum fetal assessment in pregnancies complicated by diabetes mellitus. This approach has been associated with a markedly reduced cost of health care and emotional stress for patients and their families attributable to lengthy hospitalization. These programs have used primarily biophysical testing, with twice weekly NSTs followed by a CST or biophysical profile when necessary. Most recently, Doppler studies have been investigated as a method for identifying fetal compromise. Maternal assessment of fetal activity can be used as a screening test in most surveillance programs. Essential to the success of these protocols has been our ability to monitor maternal glycemia and to maintain glucose levels in the physiologic range through aggressive therapy with insulin and diet. Reassuring tests of fetal condition are present in most diabetic women and therefore permit fetal maturation to take place before delivery.

Delivery, Obstetric↗

Development and initial experience with a manually controlled spring wire device ("Cordostat") to aid in difficult funipuncture.

Funipuncture has evolved as a useful tool in prenatal diagnosis and treatment. The ease with which it can be performed depends on placental implantation site, amniotic fluid volume, fetal presentation and activity, gestational age, and operator experience. Under select circumstances, such as hydramnios, oligohydramnios/anhydramnios, a back-up fetus/posterior placenta, or gestation of fewer than 20 weeks, funipuncture can be difficult or impossible. We have developed a new instrument, the "Cordostat," which can help the operator perform difficult funipuncture by providing stabilization and allowing intrauterine manipulation of the umbilical cord. The instrument consists of a deflecting wire guide threaded through a 19.5-guage trochar needle, which can be manually controlled to coil around and stabilize a free loop of cord. Conventional funipuncture can then be performed through a second uterine puncture. We describe use of this instrument in 12 patients undergoing second-trimester induced abortion.

Blood Specimen Collection↗

Antenatal diagnosis of sacral agenesis syndrome in a pregnancy complicated by diabetes mellitus.

The sacral agenesis syndrome is a severe congenital abnormality consisting of agenesis of the lumbar spine, sacrum, and coccyx, as well as hypoplasia of the lower extremities. It is considered the most characteristic of all congenital anomalies associated with maternal diabetes mellitus. We describe the sonographic and radiologic findings of agenesis of the lumbosacrococcygeal spine with lower limb and genital hypoplasia in the offspring of a woman with both diabetic retinopathy and nephropathy. The diagnosis was established at 25 weeks' gestation and was confirmed by radiologic evaluation of the neonate.

Abnormalities, Multiple↗

Abnormal iron distribution in infants of diabetic mothers: spectrum and maternal antecedents.

Because chronic hypoxemia causes a redistribution of iron from serum and storage pools into an expanding erythrocyte mass, and because infants of diabetic mothers are often hypoxemic in utero and have a high prevalence of polycythemia at birth, we studied iron distribution in 43 term infants of diabetic mothers. Twenty-four infants were at an appropriate size for gestational age; 19 were large for gestational age. At birth, 28 infants (65%) had abnormal serum iron profiles; eight had decreased ferritin concentrations only (stage 1), nine had decreased ferritin and increased total iron-binding capacity values (stage 2), and 11 had these serum findings plus elevated free erythrocyte protoporphyrin concentrations (stage 3). The hypoglycemic infants who were large for gestational age (n = 14) had a higher prevalence of abnormal iron profiles than euglycemic infants who were appropriate in size for gestational age (n = 20; 93% vs 50%; p = 0.009). Progressively abnormal iron profiles were associated with higher glycosylated fetal hemoglobin values, greater degrees of macrosomia, increased hemoglobin and erythropoietin concentrations, and increased erythrocyte/storage iron ratios. Erythropoietin concentrations were inversely linearly correlated with serum iron values (n = 32, r = -0.54; p = 0.003). The combined erythrocyte and storage iron pools were significantly lower in infants with abnormal iron values whose mothers were diabetic, particularly in infants of women with confirmed diabetic vasculopathy. We speculate that these findings are likely due to (1) increased fetal iron utilization during compensatory hemoglobin synthesis in response to chronic hypoxemia and (2) reduced iron transfer during late gestation complicated by diabetes.

Birth Weight↗

Management of diabetes mellitus and pregnancy: a survey of obstetricians and maternal-fetal specialists.

To ascertain current practice trends among obstetricians and maternal-fetal subspecialists regarding the care of pregnancies complicated by diabetes mellitus, a questionnaire was sent to all members of the Society of Perinatal Obstetricians (SPO) and a randomly selected group of American College of Obstetricians and Gynecologists (ACOG) Fellows. A total of 273 of 356 SPO members (77%) and 198 of 504 ACOG Fellows (39%) responded. When divided according to years post-residency (ACOGa, less than 15 years; ACOGb, 15 years or more), significant differences in practice patterns were observed for ACOG Fellows. The SPO responses were similar among these subgroups. Despite current ACOG recommendations, most clinicians practice universal screening for gestational diabetes. Significant discrepancies appear to exist between ACOGb versus ACOGa and SPO with regard to methods of glucose surveillance and the threshold for initiating insulin therapy in gestational diabetes. Intensive fetal surveillance, elective delivery, and high cesarean rates are common in pregnancies complicated by insulin-dependent diabetes mellitus, which is most often managed by a perinatologist or by an obstetrician in consultation with an internist. Few insulin-dependent patients seek preconceptional care.

Adult↗

Sonographic evaluation of fetal abdominal growth: predictor of the large-for-gestational-age infant in pregnancies complicated by diabetes mellitus.

Serial ultrasound examinations were performed during the third trimester in 79 pregnant women with diabetes to establish the onset of accelerated fetal growth. At least three ultrasound examinations were performed, with a minimum scan interval of 2 weeks. Growth curves constructed for femur length and head circumference were similar for fetuses appropriate for gestational age (n = 48) and fetuses large for gestational age (n = 31). The mean changes in femur length and head circumference (expressed as centimeters per week during the early and late third trimesters) did not differ statistically between these two groups. Abdominal circumference growth was clearly accelerated at 32 weeks' gestation in the large for gestational age group (mean +/- SD, 1.36 +/- 0.16 cm/wk) compared with the appropriate for gestational age group (0.901 +/- 0.21 cm/wk, p less than 0.001). With use of a receiver operator characteristic curve, a change in abdominal circumference of 1.2 cm/wk over the period of 32 to 39 weeks' gestation was determined to be an optimal cutoff for detecting excessive fetal growth (sensitivity 84%, specificity 85%). A change in abdominal circumference 1.2 cm/wk was present in 4/4 large-for-gestational age fetuses (less than 4000 gm), in 17/21 (81%) of fetuses with birth weights 4000 to 4499 gm, and in 5/6 (83%) whose weight exceeded 4500 gm. It appears that improved detection of the fetus large for gestational age in diabetic pregnancies may be accomplished by the use of serial ultrasonography during the third trimester.

Birth Weight↗

Shoulder soft tissue width as a predictor of macrosomia in diabetic pregnancies.

Sonographic evaluation of 43 pregnant women with diabetes mellitus was performed in the third trimester of gestation for evidence of fetal macrosomia. The width of the soft tissues of the shoulder from the skin surface to the proximal humerus was compared with previously reported measurements for their ability to predict fetal macrosomia. The abdominal circumference and shoulder soft tissue measurements were the best individual predictors of macrosomia, but a combination of an abdominal circumference greater than the 90th percentile for gestational age or a shoulder soft tissue width greater than 12 mm was the best predictor with a sensitivity of 96%, specificity of 89%, and accuracy of 93%. The shoulder soft tissue width should be evaluated for evidence of macrosomia in diabetic pregnancies.

Female↗