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Biomedical subjects

G F Reed

Publications and source records attributed to G F Reed.

At least 19 recordsLinked to original sources
PubMed1992

The Diabetes in Early Pregnancy Study: changes in cholesterol, triglycerides, body weight, and blood pressure. The National Institute of Child Health and Human Development--the Diabetes in Early Pregnancy Study.

This study examined changes in cholesterol, triglycerides, body weight, and blood pressure during pregnancy in 312 diabetic and 356 control women recruited within 21 days after conception. Cholesterol values rose in both groups but were significantly lower in diabetic women at each time point (166 vs 178 mg/dl at week 12, p = 0.0004). Triglyceride values also rose in both groups. Triglyceride levels did not differ between groups up to week 8 of gestation, but by weeks 10 to 12 they were significantly lower in diabetic women than in controls (75 vs 89 mg/dl at week 12, p = 0.0004). Although they were no heavier at entry, diabetic women gained significantly more weight between weeks 6 and 8 (p less than 0.001), resulting in a mean difference between groups of 1 kg. Systolic blood pressure increased steadily and significantly in the diabetic but not the control women (115.8 +/- 16.2 SD vs 109.3 +/- 11.8 mm Hg, p = 0.0006 at term). Diastolic blood pressure was higher in diabetic women on entry (70.7 vs 67.3 mm Hg, p = 0.0006) and throughout gestation. Significant correlations were found in the diabetic group between maternal blood pressure and lipids and infant birth weight. These newly found differences in cholesterol and triglyceride levels, weight gain, and blood pressure between type I diabetic and control women during gestation may have long-term cardiovascular implications.

Adult↗
PubMed1992

Early sonographic evaluation for fetal growth delay and congenital malformations in pregnancies complicated by insulin-requiring diabetes. National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study.

OBJECTIVE: It has been reported that early fetal growth retardation may be a useful marker for congenital malformations in diabetic pregnancies. To test this hypothesis, diabetic and nondiabetic women were sonographically evaluated during the first trimester. RESEARCH DESIGN AND METHODS: Fetal crown-rump lengths were measured sonographically at least once during the first 15 wk of pregnancy in 329 nondiabetic and 312 diabetic women. Of these, 289 nondiabetic and 269 diabetic women had sonograms before 10 wk of gestation and 283 nondiabetic and 269 diabetic women had sonograms between 10 and 15 wk of gestation. Early fetal growth delay was defined as a sonographic gestational age of greater than or equal to 6 days less than menstrual gestational age. RESULTS: The mean crown-rump lengths at 8 wk were 17.9 +/- 4.6 mm in the diabetic and 18.7 +/- 4.9 mm in the nondiabetic groups (P = 0.13). At 12 wk, the mean fetal crown-rump length was 58.5 +/- 8.8 mm for diabetic subjects and 60.6 +/- 8.7 mm for nondiabetic subjects (P = 0.04). Between 5 and 9 wk, 28 of 289 (9.7%) fetuses of nondiabetic subjects, 34 of 259 (13.1%) normal fetuses of diabetic subjects, and 2 of 10 (20%) malformed fetuses of diabetic subjects demonstrated growth delay (P = 0.31, normal vs. malformed diabetic). Between 10 and 15 wk of gestation, 28 of 283 (9.9%) fetuses of nondiabetic subjects, 32 of 256 (12.5%) normal fetuses of diabetic subjects, and 4 of 13 (30.8%) malformed fetuses of diabetic subjects demonstrated growth delay (P = 0.06, normal vs. malformed diabetic). Early fetal growth delay did not predict a reduced birth weight at term. CONCLUSIONS: Among insulin-dependent diabetic subjects who were moderately well controlled at conception, statistically significant but mild early fetal growth delay was present but did not appear to be useful clinically in predicting congenital malformations. Recommendations that growth delay demonstrated on early ultrasound be used as a predictor of congenital malformation require careful reexamination.

Adult↗
PubMed1991

Maternal postprandial glucose levels and infant birth weight: the Diabetes in Early Pregnancy Study. The National Institute of Child Health and Human Development--Diabetes in Early Pregnancy Study.

The cause of macrosomia in the infant of the diabetic woman is still not completely defined. The National Institute of Child Health and Human Development--Diabetes in Early Pregnancy Study, which recruited insulin-dependent diabetic and control women before conception, provided an opportunity to address the relationship between maternal glycemia and percentile birth weight. Data were analyzed from 323 diabetic and 361 control women. Fasting and nonfasting venous plasma glucose were measured on alternate weeks in the first trimester and monthly thereafter. Glycosylated hemoglobin was measured weekly in the first trimester and monthly thereafter. More infants of the diabetic women were at or above the 90th percentile for birth weight than infants of control women (28.5% versus 13.1%, p less than 0.001). Although first-trimester nonfasting glucose and glycosylated hemoglobin levels were positively correlated with infant birth weight (p less than 0.001 and p = 0.008), when the analyses were adjusted for the variables of the subsequent trimesters the values became insignificant, whereas the third-trimester nonfasting glucose levels adjusted for values in prior trimesters emerged as the stronger predictor of percentile birth weight (p = 0.001). After adjusting for maternal hypertension, smoking, and ponderal index, the above relationships remained. In conclusion, monitoring of nonfasting glucose levels rather than the fasting levels, which are more commonly monitored in clinical practice, are necessary to prevent macrosomia.

Blood Glucose↗
PubMed1991

Patterns of variability in the nutrient intake of nutritionally vulnerable pregnant women.

Intra/inter-individual variance ratios for energy, protein, fat and retinol-equivalent intake during the third trimester of pregnancy were calculated. Data were collected on 743 pregnant women from rural Indonesia between 1982 and 1984. Food intake of these women was directly weighed for three consecutive days per month during months 6-9 of pregnancy, yielding 7139 observations for analysis. Ratios were calculated separately for a single month of pregnancy and for the last trimester of pregnancy. The intra/inter-individual variance ratio for kilocalorie and protein intake was less than 1.0 for a single month; it was greater than 1.0 for the trimester. This suggests that women varied their intake of kilocalories and protein more over the course of their pregnancy than they did during one month of their pregnancy. Both the monthly and trimester variance ratios for fat and retinol-equivalent intake were greater than 1.0. Our findings suggest that usual mean intake during the third trimester of pregnancy can be measured with relative precision with two replicates per individual. However, more measurements are needed for regression analyses: measurement error greatly attenuated the coefficients, even though data were collected by the direct weighing method. Thus the number of measurements per individual needed in a study of nutrition and pregnancy depends on the nutrient, the period of 'usual intake' that is of interest, as well as the analytical strategy.

Dietary Fats↗
PubMed1990

Predicted reciprocal serum creatinine at age 10 years as a measure of renal function in children with nephropathic cystinosis treated with oral cysteamine.

The predicted reciprocal creatinine at age 10 years (PRC10), a parameter of renal function based upon the linear relationship between reciprocal serum creatinine and age, incorporates age, serum creatinine, and rate of renal deterioration into a single term. PRC10 measurements were employed to assess renal function in children with nephropathic cystinosis treated with oral cysteamine, a cystine-depleting agent. In 71 children receiving oral cysteamine for at least 1 year, PRC10 decreased linearly with initial serum creatinine concentration. This indicated that, although established renal damage in cystinosis was irreversible, early intervention with cysteamine therapy could favorably alter the rate of glomerular deterioration. In other analyses, mean PRC10 was shown to increase with duration of cysteamine therapy and extent of leukocyte cystine depletion. The predicted reciprocal creatinine value at a certain age can be useful in analyzing the effects of therapeutic intervention in a disease with a relatively uniform rate of renal deterioration.

Administration, Oral↗
PubMed1989

Comparison of serum placental protein hormone levels in diabetic and normal pregnancy.

Conflicting data exist concerning maternal serum concentrations of placental hormones during pregnancy in women with diabetes mellitus. To resolve some of these discrepancies, women participating in the NICHD-Diabetes in Early Pregnancy Study were studied. In this collaborative study, pregnancy was identified within 21 days of conception by serum hCG measurements. We prospectively collected 185 blood samples from 35 insulin-dependent diabetic women and 166 blood samples from 31 control women, all between 5 and 37 weeks gestation. Serum concentrations of hCG, pregnancy-specific beta-1-glycoprotein, placental lactogen, and hCG alpha were measured serially. The relationship between serum hormone, fasting blood glucose, 1-h postprandial blood glucose, and glycosylated hemoglobin concentrations was compared. Serum hCG alpha levels were significantly lower in the diabetic women than in control women at multiple time points during the first and second trimesters, while no consistent differences in the serum concentrations of hCG or pregnancy-specific beta-1-glycoprotein were found between pregnant diabetic and control women. Serum placental lactogen levels were significantly lower in diabetic women at 9-10 weeks and 20 weeks gestation. There were no correlations between fasting blood glucose, 1-h postprandial blood glucose, or glycosylated hemoglobin and any of the placental protein levels in the diabetic women. These data are consistent with a defect in synthesis and/or secretion of hCG alpha by the cytotrophoblast during the first two trimesters of pregnancy in insulin-requiring diabetic women.

Adult↗
PubMed1989

Unreliability of plasma magnesium values in asphyxiated neonates.

The severely asphyxiated neonate usually shows a decreased blood pH and, if measured, a normal plasma Mg value. This is a retrospective review of the changes in these two parameters measured 2 or 3 times in 16 asphyxiated neonates as homeostasis was reestablished. The group was comprised of all asphyxiated neonates with 2 or 3 blood pH determinations, each with a plasma Mg determination within 6 h. Repeating these two tests had been prompted by poor clinical courses that suggested acid-base imbalance and Mg deficiency. The blood pH found on first sampling (day 0.42, with 0 the first day of life) was 7.24 +/- 0.02 (normal 7.35-7.45). This increased to 7.40 +/- 0.02 a mean of 2 days later (p less than 0.001 compared to first value by t test) and was still normal 4 days later (NS, compared to second value). The plasma Mg showed an opposing trend, with the first value 1.76 +/- 0.1 mEq/l (hospital normal 1.6-2.2 mEq/l); the second value 1.38 +/- 0.06 (p less than 0.004, compared to the first value), and the third, 1.30 +/- 0.11 (NS compared with the second value). It is concluded that plasma Mg determined during acidosis may give a falsely elevated value and may mask a true Mg deficiency which can be diagnosed only after homeostasis is reestablished, as when the blood pH is normal. While some asphyxiated infants were found to be hypomagnesemic, this study does not implicate Mg deficiency in meconium aspiration or any other cause of asphyxia.

Acidosis↗
PubMed1989

Validity of the parenteral magnesium load test for mature mammals.

Because of the difficulty in accurately assessing the Mg status of a hospitalized patient, the parenteral Mg retention test may be a valuable diagnostic tool. In former studies in animal models, this test has reliably identified adult rats fed two extremes of dietary Mg, but we found no tests of intermediate levels of Mg in adult animals. As a means of assessing the validity of the parenteral Mg retention tests in adult rats, the present study was conducted to learn (1) the relationship between Mg in plasma and bone in adult mammals that had optimal nutrition at the onset of the experiment, and (2) the relationship between Mg retention and Mg in plasma and bone in those animals. Animals were fed five levels of dietary Mg from 0 to 150 mg/100 g purified diet. Parenteral Mg retention tests were conducted after 2 weeks of dietary treatment, and 18 h after the completion of the tests, plasma and bone were analyzed for Mg. We found that plasma and femur levels of Mg varied linearly under conditions of Mg deficit, indicated by a high retention of the Mg load. As the deficit diminished, both plasma and femur levels approached a limit and the slope of the curve tends to zero. Mg retention and plasma or femur Mg level was approximated by a negative exponential curve. Stated another way, the logarithmic values of Mg retention decreased approximately linearly with increase in bone or plasma Mg. It was concluded that the parenteral Mg retention test is a valid test to evaluate Mg deficiency and to identify Mg sufficiency in adult mammals.

Animals↗
PubMed1988

Lack of relation of increased malformation rates in infants of diabetic mothers to glycemic control during organogenesis.

To determine how much insulin-dependent diabetes increases a woman's risk of giving birth to a malformed infant and how that risk is influenced by metabolic control, we followed 347 diabetic and 389 control women who enrolled in the study within 21 days of conception (the early-entry group) and 279 diabetic women who entered later (the late-entry group). We detected major malformations in the infants of 4.9 percent of the early-entry diabetic women, 2.1 percent of the controls, and 9.0 percent of the late-entry diabetic women. Malformation rates were significantly higher among offspring of early-entry diabetic women than among those of controls (odds ratio, 2.45; lower one-sided 95 percent confidence limit, 1.12; P = 0.027), and higher among late-entry than among early-entry diabetic women (odds ratio, 1.91; lower one-sided 95 percent confidence limit, 1.07; P = 0.032). Mean blood glucose and glycosylated hemoglobin levels during organogenesis were not significantly higher in women whose infants were malformed. Hypoglycemia (glucose, less than or equal to 50 mg per deciliter [2.8 mmol per liter]) was not significantly more common in the same group. Hyperglycemia and glycosylated hemoglobin were not correlated with malformation. The data suggest that more sensitive measures are needed to identify the teratogenic mechanisms, or that not all malformation can be prevented by good glycemic control. Despite the increased malformation rate among infants of the early-entry diabetic women, as compared with the controls, the more favorable outcome seen in the former group as compared with the late-entry group justifies the attempt to achieve good metabolic control around the time of conception.

Blood Glucose↗
PubMed1987

Cysteamine therapy for children with nephropathic cystinosis.

We treated 93 children with nephropathic cystinosis with oral cysteamine (mean dose, 51.3 mg per kilogram of body weight per day) for up to 73 months. This agent is known to be effective in depleting cells of cystine. In our study, the mean cystine depletion from leukocytes was 82 percent. A historical control group of 55 children received either ascorbic acid (27 children) or placebo (28). At age six, 2 of 17 controls had a serum creatinine level less than 1.0 mg per deciliter, as compared with 17 of 27 patients treated with cysteamine for at least one year (odds ratio, 12.8; 95 percent confidence interval, 2.1 to 33.9). At the end of the study, creatinine clearance was higher in the cysteamine group than in the control group (38.5 vs. 29.7 ml per minute per 1.73 m2; 95 percent confidence limits on the difference, 1.8 and 15.8), even though the cysteamine group was on average 1.4 years older than the control group. Cysteamine also improved growth; those in the cysteamine group between two and three years of age grew at 93 percent of the normal velocity, as compared with 54 percent in the control group. Fourteen percent of the patients could not tolerate the taste and smell of cysteamine. Concurrent controls treated in a blinded fashion with a placebo were not included in this study. With this limitation in mind, we conclude that oral cysteamine, by depleting cells of cystine, helps maintain renal glomerular function, improves growth, and constitutes the current treatment of choice for nephropathic cystinosis.

Administration, Oral↗
PubMed1987

Glutathione metabolism in normal and cystinotic fibroblasts.

Intracellular concentrations of glutathione and activities of the enzymes gamma-glutamylcysteine synthetase, glutathione synthetase, and gamma-glutamyl transpeptidase were measured in confluent cultured human fibroblasts cell lines from 14 normal cell lines and four cystinotic cell lines. gamma-Glutamyl transpeptidase had a wide range of variability while the glutathione synthetic enzymes, gamma-glutamylcysteine synthetase and glutathione synthetase, had narrower variations and also exhibited no apparent relationship to glutathione content. No differences in the activities of these enzymes were found between normal and cystinotic cells in confluent cell cultures. The activities of the above enzymes and the cell number and content of glutathione, cystine, DNA, and total protein in two normal and two cystinotic fibroblast cell lines were measured during growth. The following growth-dependency patterns were observed: (1) gamma-glutamylcysteine synthetase activity increased markedly in lag and early log phases in both normal and cystinotic cells and decreased rapidly to low confluent levels thereafter. (2) gamma-Glutamyl transpeptidase showed the same wide range of activity noted at confluency but activities decreased in the log phase of growth, a pattern also seen in cystinotic cells. (3) Glutathione synthetase activity remained relatively constant during growth of normal cells but exhibited a peak of activity during lag and early growth of cystinotic cells. (4) Comparative glutathione levels of normal and cystinotic cells were not significantly different and exhibited similar fluctuations with time. (5) The cystine content of normal and cystinotic cells unexpectedly rose to high levels in the lag phase, then decreased to 0.1 nmol 1/2 cystine/mg protein in normal cells and to 0.3 to 1.2 nmol 1/2 cystine/mg protein in cystinotic cells during the log phase. As confluency was approached, normal cell cystine remained at low levels while cystinotic cell cystine rose to characteristically high levels of 50- to 100-fold greater than normal cells at late confluency. These studies extend our understanding of the regulation of glutathione and cystine content in cultured fibroblasts and suggest that glutathione content is closely controlled throughout the cell cycle in the face of varying activities of its anabolic and catabolic enzymes.

Cell Division↗
PubMed1987

Effect of heparin on membrane associated clathrin basketwork of cultured cells derived from the stromal-vascular fraction of mouse brown adipose tissue.

The effect of heparin treatment on clathrin basketwork of cell membranes was examined in cultured cells derived from the stromal-vascular fraction of neonatal mouse brown adipose tissue. The cytoplasmic surface of the plasma membrane of ruptured cells was examined with surface replicas. Heparin treatment significantly decreased the extent of clathrin basketwork associated with the membrane from 3.4 to 0.2%. The loss of clathrin basketwork suggests that heparin treatment of these cells affected intracellular sorting processes associated with endocytosis.

Adipose Tissue, Brown↗
PubMed1987

Prevalence, natural history and surgical treatment of exophthalmos.

The 95% confidence limits of exophthalmometer measurements have been defined by a single observer in 105 individuals who had no known thyroid disease, and found to be 10.5-18.8 mm. Measurements in 308 patients with thyrotoxicosis have shown that exophthalmos (greater than 19 mm) of one or both eyes was present in 21.3% of the patients. Among the 122 thyrotoxic patients whose exophthalmometer measurements could be performed annually for 3-19 years after correction of the thyrotoxicosis (usually with 131I), exophthalmos remained stable in 78.7%, worsened in 15.6% and became less severe in 5.7% of the patients. Transantral decompression of the orbits was performed in 15 patients with rapid subjective improvement in all and reduction in exophthalmometer measurements of 3.6 +/- 0.5 (mean +/- SEM) mm, and no serious side-effects. In view of these findings, transantral decompression should be considered more frequently in the treatment of severe or cosmetically damaging exophthalmos.

Adolescent↗
PubMed1987

Protection against the lethal effects of pentobarbital in mice by a benzodiazepine receptor inverse agonist, 6,7-dimethoxy-4-ethyl-3-carbomethoxy-beta-carboline.

The benzodiazepine receptor inverse agonist 6,7-dimethoxy-4-ethyl-3-carbomethoxy-beta-carboline (DMCM) (1.5-15 mg/kg) was administered to mice 5 min after a lethal (LD94) injection of pentobarbital. DMCM (1.5-5 mg/kg) increased short-term (1 h) survival in a dose-dependent fashion, with an optimum survival rate more than five times greater than mice receiving pentobarbital alone. Statistically significant increases in long-term (24 h) survival were also observed after both 5 and 10 mg/kg of DMCM (34 and 33%, respectively) compared with animals receiving pentobarbital alone (6%). Two doses of DMCM (5 and 2.5 mg/kg, respectively) administered 55 min apart produced an even greater increase (58%) in 24-h survival rates. Doses of DMCM that increased 1- and 24-h survival were not lethal when administered alone, and were below the dose that produced convulsions in 50% (CD50) of the animals. The protective effects of DMCM were blocked by pretreatment with the benzodiazepine receptor agonist ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo- 4H-imidazo[1,5a][1,4]benzodiazodiazepine-3-carboxylate (Ro 15-1788), which suggests the effects of DMCM are mediated through the benzodiazepine receptor. These findings suggest that DMCM or another benzodiazepine receptor ligand with full inverse agonist qualities could prove effective as an antidote for barbiturate intoxication in man.

Animals↗
PubMed1985

Benzodiazepine-receptor mediated inhibition of isolation-induced aggression in mice.

The effects of a benzodiazepine receptor agonist (diazepam), antagonist (Ro 15-1788), and an "active" antagonist [inverse agonist] (3-carboethoxy-beta-carboline) were examined in an isolation-induced model of aggression. Diazepam (4 mg/kg) and 3-carboethoxy-beta-carboline (10 mg/kg), but not Ro 15-1788, significantly inhibited aggressive behavior in this model. Ro 15-1788 (10 mg/kg) reduced the anti-aggressive actions of both diazepam and 3-carboethoxy-beta-carboline, while mice treated with a combination of diazepam and 3-carboethoxy-beta-carboline had aggression scores increased to values not significantly different from vehicle treated mice. These findings suggest that both diazepam and 3-carboethoxy-beta-carboline have anti-aggressive properties in the isolation-induced model of aggression which are mediated through CNS benzodiazepine receptors.

Aggression↗
PubMed1985

Are there adverse effects of periconceptional spermicide use?

Recent studies have suggested that spermicide exposure around conception may cause congenital malformations, reduced birth weight, or spontaneous abortion. This large, prospective study examined the risk for multiple malformation, patterns of malformations, low birth weight, preterm delivery, and spontaneous abortion in infants whose mothers used spermicides only before or after their last menstrual period, compared with a control group using other contraceptive methods. The multiple malformation rates in women using spermicides only before or after their last menstrual period were 3.8 and 4.8 per thousand, respectively. For the control groups, the corresponding rates were 5.4 and 6.4 (not significant). No pattern of malformations was found in spermicide-exposed infants. The risk of preterm delivery, the risk for producing a low-birth-weight (less than 2500 gm) infant, and the risk of spontaneous abortion were no higher in women exposed to spermicides than in women using other methods of contraception. This study finds no evidence that spermicide exposure around the time of conception is dangerous to the fetus.

Abnormalities, Drug-Induced↗
PubMed1979

The estimation of dental caries incidence in the presence of diagnostic error.

Diagnostic error in large scale screening programs for dental caries is frequent, as when teeth initially classified as carious are later diagnosed as never having been affected by caries. This paper presents a general formulation of diagnostic error in dental caries screening. The basic parameter of the formulation is the caries incidence rate. The general formulation of this paper permits an explicit comparison, in a common notation, of two specific models of diagnostic error--one due to Carlos and Senning, the other to Lu. Each model gives rise to a consistent estimator of the incidence rate. The distributional properties of these estimators had not previously been examined because of the dependence of teeth in the same mouth with respect to caries experience. Using the present formulation, the sampling scheme may be regarded as a one-stage cluster sample with mouths as clusters. This approach accounts for intracluster dependence thus permitting the derivation of an estimator of the relevant covariance matrix and a confidence interval for the incidence rate.

Dental Caries↗