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Biomedical subjects

E A Reece

Publications and source records attributed to E A Reece.

At least 55 records · Page 3Linked to original sources

Impairment of counterregulatory hormone responses to hypoglycemia in pregnant women with insulin-dependent diabetes mellitus.

Intensive insulin therapy directed at elimination of hyperglycemia is advocated during pregnancy in women with insulin-dependent diabetes mellitus. Because such treatment is complicated by frequent hypoglycemic episodes, we evaluated maternal and fetal responses in nine intensively treated pregnant women with insulin-dependent diabetes mellitus during an insulin-induced, gradual, controlled fall in plasma glucose levels. In contrast to values in nonpregnant control women, reductions in glucose to 44 +/- 2 mg/dl in pregnant diabetic patients failed to elicit an increase in glucagon levels. Epinephrine release during hypoglycemia was also markedly suppressed in the pregnant diabetic subjects (106 +/- 32 vs 327 +/- 52 pg/ml in controls, p less than 0.001). Furthermore, the plasma glucose level at which epinephrine and growth hormone were released was 5 to 10 mg/dl lower in the pregnant women with insulin-dependent diabetes mellitus (p less than 0.05). The basal fetal heart rate remained unchanged and continued to manifest accelerations during the hypoglycemic state. We conclude that the high frequency of hypoglycemia in intensively treated pregnant women with insulin-dependent diabetes mellitus may be due in part to impaired counterregulatory hormonal responses.

Adult

May-Hegglin anomaly: a rare case of maternal thrombocytopenia in pregnancy.

The May-Hegglin anomaly, a rare cause of thrombocytopenia, is an autosomal dominant disorder that may have adverse maternal and fetal consequences. We present herein a case of May-Hegglin anomaly in pregnancy. The characteristic features of this anomaly, clinical presentation, and management options are discussed.

Adult

Diabetes mellitus in pregnancy and periconceptional genetic counseling.

Gestational diabetes constitutes 90% of all pregnant diabetic patients, whereas insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) together account for the remaining 10%. Diabetes is considered a heterogeneous disease with a continuous spectrum between IDDM and NIDDM. It is believed that gestational diabetes is also a heterogeneous disorder representing, at least in part, patients who are destined to develop in later life either IDDM or NIDDM. Studies in identical twins have shown clear-cut differences in the genetic inheritance of IDDM and NIDDM. Nearly 100% of identical twins were found to be concordant for NIDDM; whereas in IDDM the concordance rate ranges between 20 and 50%. This concordant pattern indicates a higher genetic contribution in NIDDM than IDDM. Furthermore, IDDM is an HLA-linked disorder, and NIDDM is not. The exact mechanism of inheritance of IDDM and NIDDM is not known; therefore the information used in genetic counseling is based on empirical risk estimates. Recent information demonstrates that IDDM is transmitted less frequently to the offspring of diabetic mothers than diabetic fathers (1.3% versus 6%). The estimated risk of recurrence of IDDM to offsprings with one already affected sibling and unaffected parents is 5 to 6%. Additionally, the empirical risk of NIDDM first-degree relatives developing diabetes is much higher than the observed in IDDM relatives, 15% for first-degree relatives and 60 to 75% when both parents have NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 1

Embryoscopy: new developments in prenatal medicine.

Embryoscopy is a new technique that allows direct visualization of the embryo/fetus as early as the first trimester. A rigid fiberoptic endoscope is passed transcervically into the extracoelomic cavity and has been utilized to identify developmental milestones from weeks 4 to 8 following conception. All major external and internal structures develop during this period. With this technique, it is possible to both identify anomalies and confirm those diagnosed by ultrasound. Fetal blood sampling has also been preformed utilizing this technology and has established the feasibility of access to the human embryonic circulation. Future applications for embryoscopy include first-trimester prenatal diagnosis and therapeutic interventions such as gene or cell therapy at a time when the embryo is immunologically tolerant.

Embryonic and Fetal Development

Does intensive glycemic control in diabetic pregnancies result in normalization of other metabolic fuels?

Intensive treatment of insulin-dependent diabetes mellitus during pregnancy often normalizes plasma glucose levels. However, it is unclear whether this adversely affects other metabolic fuels that are essential to normal fetal growth and development. Metabolic studies were conducted after the subjects ingested a standardized mixed meal during each trimester in 7 normal and 15 insulin-dependent diabetic pregnant women. The latter were treated with continuous subcutaneous insulin infusion or multiple injections, which were adjusted to achieve strict glucose control throughout pregnancy. Insulin, alanine, branched-chain amino acids, triglycerides, free fatty acids, and ketones were measured every 15 to 30 minutes before a standardized breakfast and for 150 minutes after the breakfast. Patients with insulin-dependent diabetes mellitus were studied while they received their unusual insulin dosages. Fasting glucose levels (87 +/- 7 mg/dl) and glucose levels 150 minutes after the meal (112 +/- 11 mg/dl) were near normal. However, normoglycemia was achieved at the expense of increased plasma insulin levels (area under insulin response curves, p less than 0.01, vs nondiabetic curves). Nevertheless, fasting and post-prandial plasma branched-chain amino acids, alanine, and free fatty acids were similar in both groups. Fasting cholesterol, triglyceride, and ketone levels were also normalized. We conclude that normalization of circulating amino acids and lipids in conjunction with correction of hyperglycemia may contribute to favorable outcomes in infants of intensively treated diabetic mothers.

Adult

Cardiac growth in fetuses of diabetic mothers with good metabolic control.

To evaluate cardiac growth in fetuses of those diabetic mothers with good metabolic control, we examined M-mode echocardiographic measurements obtained from 24 fetuses of diabetic mothers (FODM) and compared these with measurements from 31 normal fetuses of similar gestational age. Fetuses were grouped into three gestational periods: 20 to 26 weeks, 27 to 33 weeks, and 34 to 40 weeks. The mothers were believed to have good metabolic control on the basis of mean daily glucose profiles and glycosylated hemoglobin A (HbA1C) values of approximately 110 mg/dl (610 mumol/L) and 7.5%, respectively, before fetal scanning, and estimated fetal weight similar to that of normal fetuses during all three gestational periods. Both FODM and normal fetuses had significant increases in M-mode measurements from period 1 to period 3, but in FODM, cardiac hypertrophy developed by late gestation (period 3). This involved the interventricular septum (6.1 +/- 0.7 vs 4.9 +/- 0.3 mm, p less than 0.05), right ventricular free wall (5.7 +/- 0.8 vs 3.2 +/- 0.3 mm, p less than 0.01), and left ventricular free wall (6.4 +/- 0.6 vs 3.3 +/- 0.4 mm p less than 0.01). The interventricular septum/right ventricular free wall ratio was similar, whereas the interventricular septum/left ventricular free wall ratio in FODM was smaller by period 3 (1.0 +/- 0.1 vs 1.6 +/- 0.1, p less than 0.05). The right ventricular diastolic dimension was similar, but the left ventricular diastolic dimension was significantly smaller in FODM during periods 2 and 3 (8.2 +/- 1.2 vs 12.2 +/- 0.7 mm, p less than 0.05). Strict metabolic control did not prevent FODM from having abnormal cardiac growth. We conclude that good metabolic control results in normal estimated fetal weight but that FODM remain at risk for mild global cardiac hypertrophy and altered diastolic dimensions.

Blood Glucose

Assessment of carbohydrate tolerance in pregnancy.

A review is given of the various methods of assessing carbohydrate tolerance in pregnancy. Oral glucose tolerance screening and diagnostic tests have been in use for more than 25 years. They are easily administered, relatively inexpensive, and present reasonable sensitivity; therefore, they continue to be used quite extensively. However, lack of reproducibility of the results and side effects such as nausea, vomiting, and headache have led to the use of alternate methods including glucose polymer (Polycose) and standard breakfast meals. These methods have been reported to present satisfactory results in clinical practice. Glycosylated hemoglobin (HbA1c) and fructosamine assays are also alternate forms of testing carbohydrate metabolism HbA1c measurement have been proven insensitive as a screening test for gestational diabetes, while their use as an index of overall glucose control remains valuable. The role of fructosamine in the assessment of carbohydrate intolerance remains controversial with conflicting claims made by various investigators regarding its sensitivity in detecting gestational diabetes and its response to alterations in glycemic control. In this review, the relative advantages and disadvantages of each glucose tolerance test are discussed and recommendations are given regarding their utility in pregnancy.

Dietary Carbohydrates

Insulin-dependent diabetes mellitus and immunogenetics: maternal and fetal considerations.

It has now become clear that certain HLA antigens are associated with disease susceptibility more than any other genetic markers. Insulin-dependent diabetes mellitus (IDDM or type I) is an HLA-associated condition. Moreover, there is evidence to show that IDDM is a genetically programmed autoimmune disease. Studies of the HLA-DR region have shown a strong association with IDDM, with over 90 per cent of IDDM patients possessing DR3 and/or DR4. Although the HLA-DR region is a major component in the inherited disease susceptibility, it is not the only gene region involved. Recent studies demonstrated that HLA-DQ may be more closely linked to the disease locus than HLA-DR. Sequence analysis of the HLA-DQ3 gene products suggest that a single amino acid (aspartic acid) at position 57 is uniquely important for determining susceptibility or resistance to IDDM. Although there is a strong association of certain HLA loci with IDDM, it may not explain nor account for all the genetic susceptibility to the disease. It seems that 60 per cent of the genetic basis of IDDM is related to the HLA gene (chromosome 6) and another 40 per cent is non-HLA-associated (i.e., chromosomes 2, 7, 11, and 14). Even though great progress has been made in the understanding of the genetics of IDDM, the mode of inheritance of the disease remains controversial. The present review discusses various aspects of the autoimmune process believed to be involved in pancreatic beta cell destruction in individuals genetically susceptible to IDDM. The possible modes of inheritance and new data regarding estimated risks of transmitting the disease are presented.

Chromosome Mapping

A prospective longitudinal study of growth in twin gestations compared with growth in singleton pregnancies. I. The fetal head.

Since the available data on growth in twin gestations have been derived from retrospective cross-sectional studies with varying results, a prospective longitudinal study was initiated to assess fetal head growth in twin gestations as compared to singleton pregnancies. In uncomplicated twin gestations, growth of the fetal head, based on the increment in growth over time and the rate of growth throughout pregnancy, was found not to be significantly different than in singleton pregnancies. In light of these findings, current nomograms derived from measurements obtained in singleton pregnancies remain useful for evaluating fetal head growth in twin gestations.

Cephalometry

A prospective longitudinal study of growth in twin gestations compared with growth in singleton pregnancies. II. The fetal limbs.

The assessment of fetal growth is crucial in twin gestations, since the information gained often has an impact on pregnancy management. The measurement of the fetal anatomy by ultrasound enables us to follow the growth and development of the fetus. However, the pattern of fetal growth in twin gestations has not yet been precisely characterized in prospective studies. In this light, we initiated a prospective longitudinal study and sonographically examined 35 patients with twin gestations every 3 weeks from the 15th week until delivery. Multiple biometric parameters were measured, including the femur length, humerus length, ulna length, and tibia length. The results of our study showed that growth of these long bones was not significantly different between twins A and B throughout gestation and that the growth velocity between twins and singletons was not significantly different. The incremental growth, although significantly less in twins than in singletons, was so small that it was judged not to be of clinical importance to warrant the generation of separate nomograms for the evaluation of growth in twin gestations.

Anthropometry

Maternal indomethacin therapy in the treatment of polyhydramnios.

Fifteen patients with polyhydramnios and clinical symptoms related to excess amniotic fluid volume were treated with indomethacin therapy that was started at a mean gestational age of 27.4 +/- 2.79 weeks and discontinued at a mean gestational age of 32.9 +/- 1.83 weeks. Patients were treated with 2.0 to 2.2 mg of indomethacin per kilogram of body weight per day, either orally or by rectal suppositories. No therapy was administered after 35 weeks, and the duration of therapy was no longer than 4 weeks. The majority of fluid reduction occurred within the first week of treatment. Subsequently, a smaller but steady reduction of fluid was observed. All patients were delivered after 38 weeks with a mean birth weight of 3543 +/- 586.3 gm. Examinations of newborns at birth and follow-up at 3 months, 6 months, and 1 year revealed no adverse effects of indomethacin administration.

Administration, Oral

Embryoscopy: description and utility of a new technique.

Embryoscopy is a new technique for direct visualization of the first-trimester conceptus. A rigid fiberoptic endoscope is passed transcervically under ultrasonographic guidance into the chorionic cavity. Anatomic scrutiny and direct access to the developing embryo are made possible by this technique.

Endoscopes

Recurrent adverse pregnancy outcome and antiphospholipid antibodies.

Antiphospholipid antibodies, which include lupus-like anticoagulant and anticardiolipin antibody, have been linked to a number of adverse pregnancy outcomes, although their exact pathogenic mechanisms remain poorly defined. The relative risk of complications such as intrauterine growth retardation, spontaneous abortions, and stillbirth in patients with antiphospholipid antibodies also remains undetermined. Heightened attention has been focused on the association, leading to investigations into the pathogenesis. Uncontrolled studies have also explored therapeutic regimens such as aspirin, steroids, and heparin, and clinical trials have used various treatment protocols. Although knowledge into the association of antiphospholipid antibodies and recurrent adverse pregnancy outcome is limited and continues to evolve, this association provides new insights into the disease and offers promise for pharmacologic prophylaxis. In this article, current concepts on pathogenesis, diagnosis, and therapy are reviewed and recommendations are made for clinical care of these patients.

Adrenal Cortex Hormones

Sonographic assessment of growth of the fetal head in diabetic pregnancies compared with normal gestations.

A longitudinal ultrasound study was conducted in 45 insulin-dependent diabetic patients who maintained good glycemic control (mean plasma glucose less than 120 mg/dl) throughout most of their pregnancy in order to assess growth of the fetal head in the presence of euglycemia. Patients with and without vasculopathy were found to be comparable with regard to their glycemic control, medical and obstetric complications, as well as incremental growth and the velocity of growth of the fetal biparietal diameter (BPD). When compared with the control group, the velocity of growth of the BPD was not significantly different throughout pregnancy. However, the actual increment in BPD growth remained less than that of the control fetuses, especially during the second trimester when a significant statistical difference was found. Possible explanations may include delayed ovulation, reduced growth velocity in the first trimester, or constitutionally smaller embryos among the diabetic group. The pattern of BPD growth among diabetics was best described by a third degree polynomial regression equation. These results demonstrate that in well-controlled diabetics, although the increment in BPD was less than controls, the growth pattern of the fetal BPD was similar among the White classes B to FR, and the velocity of growth of the BPD was similar among diabetics and nondiabetics.

Blood Glucose

Sonographic evaluation of the normal developmental anatomy of fetal cerebral ventricles. IV.: The posterior horn.

A prospective ultrasound study was conducted in 160 normal pregnant women with gestational ages ranging from 14 to 40 weeks. Several fetal biometric measurements were obtained, including the posterior horn width (PHW) and the cerebroposterior horn distance (CPHD) of the lateral ventricles. Curvilinear relationships were found between the gestational age and the ratio of the PHW/CPHD (r = 0.665, p less than 0.0001); and the PHW/hemispheric width (HW), (r = 0.716, p less than 0.0001) and also between the biparietal diameter and the PHW/CPHD ratio (r = 0.649, p less than 0.0001), and the PHW/HW ratio (r = 0.732, p less than 0.0001). A correlation in growth was also observed between the femur length and the PHW/CPHD (r = 0.660, p less than 0.0001), and the PHW/HW (r = 0.734, p less than 0.0001). Nomograms of the PHW, CPHD, and the ratio of PHW/CPHD against gestational age were generated. The establishment of normal indices of the posterior horn provides new, precise, and comprehensive data that will serve as a standard against which the evaluation of early abnormal ventricular growth and anomalous development of the central nervous system may be compared.

Cerebral Ventricles

Does pregnancy alter the rate of progression of diabetic nephropathy?

The effect of gestation on the rate of decline in renal function was studied in 11 pregnancies complicated by diabetic nephropathy. For each pregnancy, serum creatinine levels were available within 4 years before pregnancy, during pregnancy, and within 4 years after delivery. Although all of these patients were hypertensive and had increased proteinuria during pregnancy, the mean serum creatinine just prior to conception (1.3 +/- 0.5 mg/dl) and the last follow-up value (1.2 +/- 0.3 mg/dl) were not significantly different. When the inverse of serum creatinine (1/Scr) was used to estimate creatinine clearance, the renal function was either improved or remained stable in the majority of the pregnancies (7 of 11). The observed decline in renal function through the end of follow-up appeared to be consistent with the expected natural course of diabetic nephropathy in the absence of pregnancy. Furthermore, the slope for inverse serum creatinine before and after pregnancy was not significantly different. In conclusion, pregnancy in patients with mild to moderate diabetic nephropathy does not seem to accelerate the rate of decline in renal function.

Adult