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Biomedical subjects

M B Landon

Publications and source records attributed to M B Landon.

At least 19 recordsLinked to original sources
PubMed2006

Differentiation-dependent regulation of the cyclooxygenase cascade during adipogenesis suggests a complex role for prostaglandins.

AIM: A thorough understanding of the mechanisms of adipocyte differentiation and metabolism is important for the prevention and/or treatment of obesity and its complications, including type 2 diabetes mellitus. A complex role for prostaglandins (PGs) in adipogenesis is suggested. We examined the expression and cellular localization of enzymes in the cyclooxygenase (COX) cascade that synthesize PGs as well as the PG profile as a function of differentiation status in 3T3-L1 cells. METHODS: Murine 3T3-L1 preadipocytes were used as a model for studies of adipocyte differentiation induced by a hormone cocktail and compared with the parental fibroblastic line NIH 3T3. Both cell lines were incubated in maintenance medium or differentiation medium. Nine days after differentiation, the expression of enzymes in the COX cascade was evaluated by immunoblot analysis, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunocytochemistry, and PG formation was examined using enzyme immunoassay. RESULTS: A differentiation-dependent diminution of COX-1 and COX-2 mRNA and cognate proteins in 3T3-L1 cells was observed. PG release, including PGE(2), 6-keto PGF(1alpha), PGD(2) and 15d-PGJ(2), significantly decreased following differentiation in 3T3-L1 cells (anova/Tukey, p < 0.05). However, microsomal PGE synthase (mPGES) and lipocalin-type PGD synthase (L-PGDS) were selectively upregulated. Immunocytochemistry revealed that COX-1 and COX-2 became intracellularly more diffuse upon differentiation, whereas mPGES was redistributed to the nuclear compartment. CONCLUSIONS: Regulation of PG formation and COX-2 expression in 3T3-L1 cells is differentiation-dependent and involves changes in the levels of gene expression of the individual isoforms as well as redistribution of the enzymes within cellular compartments.

3T3-L1 Cells↗
PubMed2006

Disseminated intravascular coagulation following selective termination in a twin pregnancy. A case report.

OBJECTIVE: Coagulation abnormalities after single fetal demise are well described, but similar cases had not been previously reported following therapeutic selective termination. CASE: A 23-year-old G(3) P(2001) with a monochorionic-diamnionic twin pregnancy underwent selective termination at 20 4/7 weeks for severe twin-twin transfusion syndrome. Her fibrinogen thereafter decreased and she developed disseminated intravascular coagulopathy with pathological bleeding during a cesarean section. The maternal coagulopathy resolved postpartum. CONCLUSION: Coagulation disorders can follow selective termination. Recommendations to serially follow coagulation parameters after these procedures, however, cannot be based upon a single case.

Adult↗
PubMed2002

A planned randomized clinical trial of treatment for mild gestational diabetes mellitus.

OBJECTIVE: A planned study is described which will determine whether a benefit exists for the treatment of mild carbohydrate intolerance during pregnancy. METHODS: A randomized clinical trial of women with mild gestational diabetes will compare perinatal outcomes in those receiving diet therapy and insulin as required versus those randomized to no specific treatment. RESULTS: The primary outcome of this study will be a composite of neonatal morbidity in the treatment and control groups. CONCLUSIONS: A randomized treatment trial of mild gestational diabetes mellitus will clarify whether identification and treatment of mild gestational diabetes mellitus reduces perinatal morbidity. This information will aid in selecting appropriate thresholds for the treatment of gestational diabetes mellitus.

Cohort Studies↗
PubMed2002

Fetal surveillance in pregnancy complicated by diabetes mellitus: is it necessary?

This article provides a literature review and opinion concerning the need for fetal surveillance in diabetic pregnancy. Low rates of intervention for suspected fetal jeopardy accompany well-controlled diabetic pregnancies in the absence of vascular disease or hypertension. The clinical utility of routine tests of fetal surveillance in uncomplicated type 1 and type 2 diabetic and gestational diabetic pregnancy has not been established. A randomized trial designed to establish whether a benefit exists to fetal testing in this population is not feasible, largely owing to sample size considerations.

Blood Glucose Self-Monitoring↗
PubMed2000

Functional urinary tract obstruction developing in fetuses with isolated gastroschisis.

OBJECTIVE: To evaluate the frequency and natural history of urinary tract abnormalities developing in fetuses presenting with initially isolated gastroschisis. METHODS: Serial ultrasounds were performed prospectively on fetuses identified by our prenatal diagnosis program as having a gastroschisis. When abnormalities in the urinary tract were identified prenatally, newborns were evaluated by a pediatric urologist. RESULTS: Over a 1-year period four out of 12 fetuses with gastroschisis developed deformations of the urinary tract. In three fetuses the bladder herniated through the abdominal wall defect. Two also had upper tract dilatation. A fourth fetus developed bilateral hydronephrosis with a normally situated bladder. Once the gastroschisis was repaired none of the newborns had evidence of structural obstruction of the urinary tract, however, hydronephrosis with or without reflux persisted for several months. CONCLUSIONS: Deformations of the fetal urinary tract can develop secondary to gastroschisis. They do not appear to represent separate malformations and evaluation with fetal karyotyping may not be indicated. When hydronephrosis is present ongoing urologic evaluation of the neonate is indicated.

Adult↗
PubMed1998

Management of infants of diabetic mothers.

OBJECTIVE: To describe the clinical outcome of infants born to mothers with gestational diabetes mellitus (GDM) and preexisting insulin-dependent diabetes mellitus (IDDM). SETTING: A tertiary care regional perinatal center with a specialized diabetes-in-pregnancy program. DESIGN: Case series. RESULTS: Five hundred thirty infants were born to 332 women with GDM and 177 women with IDDM. Thirty-six percent of these 530 newborns were large for gestational age, 62% were appropriate for gestational age, and only 2% were small for gestational age. Seventy-six (14%) of all infants were born before 34 weeks' gestation, 115 (22%) between 34 and 37 weeks of gestation, and 339 (64%) at term. Two hundred thirty-three infants (47%) were admitted to the neonatal intensive care unit due to respiratory distress syndrome (RDS), prematurity, hypoglycemia, or congenital malformation. Hypoglycemia (more common among infants of maternal diabetic classes C through D-R) was documented in 137 (27%) of all newborns. One hundred eighty-two infants (34%) had RDS of varying severity. Polycythemia (5% of infants), hyperbilirubinemia (25%), and hypocalcemia (4%) were other morbidities present. Two hundred forty-four infants were admitted for routine care and enteral feedings. Forty-three of these newborns required subsequent transfer to the neonatal intensive care unit for treatment of hypoglycemia (16 cases), RDS (19 cases), or both (8 cases). Routine care failures were more common among infants whose mothers had advanced diabetes, but less frequent among breast-fed infants. CONCLUSIONS: With modern management, fewer morbidities can be expected in infants of diabetic mothers. Those infants born to women with IDDM remain at risk for hypoglycemia, which can be treated in one half of the cases by enteral feedings alone. The majority of cases of RDS are mild and require short admissions to special care nurseries. Optimal care of infants of diabetic mothers is based on prevention, early recognition, and treatment of common conditions. Severe congenital malformations, significant prematurity, RDS, recurrent hypoglycemic episodes, and asymptomatic infants of women with advanced IDDM should be admitted to special care nurseries. Breast-feeding among women with GDM and IDDM should be encouraged.

Adult↗
PubMed1996

Perinatal outcome and long-term follow-up associated with modern management of diabetic nephropathy.

OBJECTIVE: To determine outcomes in pregnancies complicated by class F diabetes mellitus cared for at a single center, and to assess renal function in these women. METHODS: A retrospective review (1988-1994) of all pregnant women with class F diabetes was performed, as well as an evaluation of current renal function. RESULTS: Forty-six pregnancies in 45 women reached a mean (+/- standard deviation) gestational age of 35.8 +/- 2.3 weeks, with a mean birth weight of 2623 +/- 818 g. No deliveries occurred before 30 weeks and 39 (84%) were at least 34 weeks. Perinatal survival was 100%. Women with initial serum creatinine exceeding 1.5 mg/dL or more than 3 g/24 hours proteinuria had an increased risk of early delivery, lower birth weight, preeclampsia, and cesarean delivery. Twenty-four individuals (53%) developed preeclampsia and seven met criteria for severe preeclampsia. By the third trimester, 26 women(58%) had greater than a 1 g/24 hour increase in proteinuria and 16 (36%) demonstrated more than a 15% fall in creatinine clearance. Follow-up was obtained in 34 subjects with a mean duration of 2.8 years. Individuals with initial creatinine clearance greater than 90 mL/minute and less than 1 g of protein per 24 hours had less loss of renal function at follow-up, as measured by creatinine clearance. At follow-up, mean protein excretion had decreased 1.9 g/24 hours from third-trimester values, but eight women (24%) maintained protein excretion exceeding 3 g/24 hours. CONCLUSION: Modern management of class F patients can result in good perinatal outcomes. Renal function studies early in pregnancy can be used to define the risk of perinatal morbidity and long-term progression of renal disease.

Adult↗
PubMed1996

Ketoacids attenuate glucose uptake in human trophoblasts isolated from first-trimester chorionic villi.

OBJECTIVE: The objective of this study was to evaluate the hypothesis that ketoacids (acetoacetic acid and beta-hydroxybutyrate) diminish glucose transport in trophoblasts cultured from first-trimester chorionic villi. STUDY DESIGN: First-trimester trophoblasts were obtained by transabdominal chorionic villus sampling for subsequent cytogenetic analysis. The cells were established as a continuous line exhibiting trophoblast characteristics. Trophoblasts were cultured in Ham's F12/Dulbecco's modified Eagle's medium (1:1) supplemented with 15% fetal bovine serum. Experiments were initiated by a 24-hour preincubation in serum-free Ham's F12/Dulbecco's modified Eagle's medium followed by incubation with ketoacids (acetoacetic acid and beta-hydroxybutyrate, 0 to 10 mmol/L) in the presence or absence of insulin-like growth factor-I (100 ng/ml). The cells were challenged with 2-deoxy-[1,2-3H]D-glucose (0.1 mmol/L) for 5 minutes and then cell-associated radioactivity was measured. Total ribonucleic acid was extracted from cells incubated with ketoacids in the presence or absence of insulin-like growth factor-I, and Northern blots were probed with a phosphorus 32-labeled complementary deoxyribonucleic acid fragment encoding the rat GLUT 1. RESULTS: Ketoacids caused a dose-dependent inhibition of glucose transport. At 5 mmol/L acetoacetic acid there was a > 50% reduction in the rate of glucose transport in both control and insulin-like growth factor-I-treated cells. The diminution in glucose uptake by trophoblasts was not due to cellular toxicity of the ketoacids because there was no significant difference in trypan blue exclusion or lactate dehydrogenase release between control and ketoacid-treated cells. Northern analysis revealed that the steady-state expression of GLUT1 messenger ribonucleic acid was diminished in ketone-treated cells, but this effect was overcome by coincubation of cultures with insulin or insulin-like growth factor-I. CONCLUSIONS: These results indicate that ketoacids can suppress the uptake of glucose into first-trimester human trophoblasts. Because ketoacidosis in pregnant women with diabetes mellitus is a frequent clinical consequence of poor metabolic control, it is possible that elevated levels of acetoacetic acid and beta-hydroxybutyrate may impair the transport of glucose across the placental trophoblast and into the fetal circulation.

Acetoacetates↗
PubMed1996

Prenatal detection of fetal anomalies in pregnancies complicated by insulin-dependent diabetes mellitus.

OBJECTIVES: We evaluated the clinical utility of a comprehensive program of prenatal diagnostic testing for congenital anomalies in pregnancies complicated by insulin-dependent diabetes mellitus. STUDY DESIGN: Data were retrospectively analyzed from 289 diabetic women and their newborns from August 1987 to July 1993. Our protocol included initial hemoglobin A1 and maternal serum alpha-fetoprotein determinations and comprehensive fetal ultrasonography inclusive of a standard four-chamber view of the heart and detailed multiimage fetal echocardiography. RESULTS: Anomalies were identified in 29 of 289 (10%) fetuses and neonates: 12 cardiac only, 14 noncardiac, and 3 combined. In 21 of the 29 (72%) neonates the anomalies were detected prenatally. Twelve of 15 (80%) cardiac and 10 of 17 (59%) noncardiac lesions were identified prenatally. Cardiac lesions, especially of the cardiac septum and great vessels, accounted for 50% of all fetal defects. Malformations of the neuroaxis, skeleton, and genitourinary system were also detected. There were six neonatal deaths and four therapeutic pregnancy terminations associated with congenital anomalies. Although the hemoglobin A1 level was statistically significantly increased in 22 mothers of anomalous fetuses (p = 0.017), the actual difference between affected and nonaffected pregnancies was not clinically meaningful and much overlap occurred. Although 96% of women with a normal hemoglobin A1 level were delivered of normal infants, only 14% of those with an elevated value had a malformed fetus. Similarly, although 89% of gravid women with a normal maternal serum alpha-fetoprotein level were delivered of nonaffected fetuses, only 7.3% of patients with an elevated value had a malformed fetus. For the detection of cardiac defects, the sensitivity of the four-chamber view compared with detailed multiimage fetal echocardiography was 33% and 92%, respectively. CONCLUSIONS: This study demonstrates the utility of a comprehensive program to detect fetal anomalies in pregnancies complicated by diabetes mellitus.

Congenital Abnormalities↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

Accuracy and modifying factors for ultrasonographic determination of fetal weight at term.

OBJECTIVE: To determine the accuracy of various sonographic formulas for estimating fetal weight at labor. METHODS: We evaluated prospectively four published equations by Hadlock et al, Shepard et al, Rose and McCallum, and Sabbagha et al, as well as clinical examination for accuracy in determining fetal weight during labor. Two hundred twenty-three patients at 35-42 weeks' gestation underwent sonographic examination. Amniotic fluid index (AFI), placental location, maternal weight, and fetal station were recorded for each study. RESULTS: The Hadlock and Shepard equations both had a lower percentage of error than the Sabbagha formula (6.1%/204 g and 6.2%/200 g respectively, versus 7.8%/271 g; P < .007). For all four equations, 70-79% of the fetal weight predictions were within 10% of actual birth weight. Sensitivities for detecting birth weights greater than 3800 g varied greatly (11-76%), whereas specificities for detecting birth weights less than 3800 g exceeded 88%. For most equations, AFI, placental location, and maternal weight did not affect predictive accuracy. The error in weight estimation varied between 6.3-8.1% in patients with oligohydramnios. Biparietal diameter (BPD) could not be measured in approximately two-thirds of the patients studied. CONCLUSION: Using any of the four standard equations or clinical examination, accurate estimation of fetal weight can be achieved for patients in labor, even in the presence of ruptured membranes. Since the Hadlock equation does not rely on BPD measurements, it appears to be both the most accurate and clinically useful method for predicting fetal weight for patients in labor at term.

Adolescent↗
PubMed1994

Cervical sonography in preterm labor.

OBJECTIVE: To improve the accuracy of the diagnosis of preterm labor by comparing transvaginal sonography to digital examination of the cervix. METHODS: We performed transvaginal sonography in women with preterm labor who had completed a course of parenteral tocolysis. Cervical length was measured according to criteria reported previously. Cervical sonographic findings were not used in diagnosis or management. Sonographic cervical length was compared to digital assessment of dilation and effacement to assess the risk of preterm birth after treatment for preterm labor. RESULTS: Forty-eight singleton and 12 twin gestations were studied. Thirty women were nulliparous and 30 were parous. The mean (+/- standard deviation) gestational age was 31.1 +/- 2.7 weeks (range 24-35) at the examination and 35.6 +/- 2.9 weeks (range 26-43) at delivery. Twenty-four subjects delivered before 36 weeks' gestation and 36 delivered at or after 36 weeks. Cervical sonography was distinctly superior to digital assessment of dilation and effacement as a test for delivery before 36 weeks, when compared using receiver operating characteristic curves. This analysis indicated a cervical length of 30 mm as the best cutoff to maximize sensitivity and specificity. All 24 subjects who delivered preterm had cervical lengths less than 30 mm. Cervical sonography was especially useful in selecting women with preterm labor who would not deliver prematurely, ie, a high negative predictive value. None of 15 women whose cervical length was 30 mm or more delivered spontaneously before 36 weeks. CONCLUSION. Among women treated for preterm labor, a cervical length of at least 30 mm predicted a low likelihood of preterm birth. Cervical sonography may improve the accuracy of diagnosis in women treated for preterm labor.

Adult↗