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Biomedical subjects

L B Holmes

Publications and source records attributed to L B Holmes.

At least 109 records · Page 6Linked to original sources
PubMed1989

Reporting accuracy among mothers of malformed and nonmalformed infants.

The potential for recall bias in case-control studies is a common concern. The authors assessed whether recall bias was present in exposure information reported at postpartum interview by mothers of malformed and nonmalformed infants who delivered at Brigham and Women's Hospital, Boston, during 1984. Accuracy of exposure reporting was measured by comparing interview data with exposure information documented during pregnancy in obstetric records. The authors' measure of recall bias, relative sensitivity (RS), is the ratio of exposure-reporting accuracy for mothers of malformed infants to that of mothers of nonmalformed infants. Relative sensitivity estimates that are greater than 1.0 indicate that mothers of malformed infants are more accurate reporters than mothers of nonmalformed infants. Relative sensitivity was estimated for eight exposure factors: antibiotic or antifungal drug use (RS = 1.2), urinary tract or yeast infection (RS = 2.7), history of infertility (RS = 1.4), use of birth control after conception (RS = 7.6), elective abortion history (RS = 1.1), any over-the-counter drug use (RS = 1.0), spotting or bleeding (RS = 1.2), and nausea or vomiting (RS = 0.8) These data suggest the presence of recall bias for some exposure factors. The authors advise the use of malformed controls to reduce potential recall bias in case-control studies of selected malformations and many etiologic factors.

Abortion, Induced↗
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

The prenatal sonographic features of Noonan's syndrome.

The sonographic findings in four infants with Noonan's syndrome are described. All four fetuses had cystic hygromata located laterally along the cervical spine and normal karyotypes. Three of the four pregnancies were complicated by polyhydramnios and those three fetuses had associated pleural effusions. One fetus developed frank hydrops and did not survive, a clinical course that appears to be part of the clinical spectrum of Noonan's syndrome. The diagnosis of Noonan's syndrome was given serious consideration prenatally based on the sonographic findings and normal karyotype and confirmed at birth in all four cases. Three of the infants survived.

Adult↗
PubMed1988

Incidence of spontaneous abortion among normal women and insulin-dependent diabetic women whose pregnancies were identified within 21 days of conception.

Whether pregnant women with insulin-dependent diabetes mellitus have an increased risk of spontaneous abortion is controversial. To address this question, we enrolled 386 women with insulin-dependent diabetes and 432 women without diabetes before or within 21 days after conception and followed both groups prospectively. Sixty-two diabetic women (16.1 percent) and 70 control women (16.2 percent) had pregnancy losses (odds ratio, 0.99; 95 percent confidence interval, 0.67 to 1.46). After adjustment for known risk factors for spontaneous abortion, the rate was still not significantly higher in the diabetic group (odds ratio, 0.91; 95 percent confidence interval, 0.59 to 1.40). Nonetheless, among the diabetic women, most of whom had good metabolic control, those who had spontaneous abortions had higher fasting and postprandial glucose levels in the first trimester than those whose pregnancies continued to delivery (P = 0.01 for fasting glucose levels and P = 0.005 for postprandial levels). In the small subgroup of diabetic women with poor control, who had elevated values for glycosylated hemoglobin in the first trimester, each increase of 1 SD above the normal range was associated with an increase of 3.1 percent in the rate of pregnancy loss (95 percent confidence interval, 0.6 to 5.6). We conclude that diabetic women with good metabolic control are no more likely than nondiabetic women to lose a pregnancy, but that diabetic women with elevated blood glucose and glycosylated hemoglobin levels in the first trimester have a significantly increased risk of having a spontaneous abortion.

Abortion, Spontaneous↗
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↗
PubMed1988

Acetazolamide: maternal toxicity, pattern of malformations, and litter effect.

Thirty litters of C57BL 6J mice were administered intraperitoneally one of four doses (0, 500, 750, and 1,000 mg/kg maternal weight) of acetazolamide on day 9 of gestation. The fetuses were removed on day 18 and fixed, stained, cleared, and examined for the pattern of malformations. The forelimb postaxial limb deficiency was the most common abnormality, but forelimb postaxial polydactyly and a postaxial deficiency in the hindlimb were also observed. Males were significantly more likely to be malformed than females at all doses, in contrast to the predominance of females observed in rat fetuses exposed to acetazolamide (Scott et al.: Teratology 6:239-240, '73). The occurrence of limb malformations did not correlate with maternal weight loss, the birth weight of the fetus, or the position of the fetus in the uterus. A "litter effect" was demonstrated in that there was a nonuniform distribution of litters with different proportions of malformed fetuses.

Abnormalities, Drug-Induced↗
PubMed1988

Pattern of arteries in the hindlimbs of hybrid mice.

The pattern of the arterial system has been studied in the hindlimbs of adult male and female mice in a hybrid strain. A technique was developed to inspect the distribution pattern after the vessels were injected with a blue polymer, the bone was stained with alizarin red S, and the soft tissue was cleared to transparency. Substantial variations were identified in the point of origin of 6 of 41 arterial branches; extra vessels and absence of vessels were uncommon. The types of arterial differences identified in normal adult mice were different from those identified in mice with absence of the tibia, which have absence of major arteries, including the popliteal and posterior tibial arteries.

Angiography↗
PubMed1988

Comparison of two methods for linear measurement of ossified tissue in cleared mouse fetuses.

Two methods of measuring cranial structures, the direct method and a photographic method, have been compared in day 18 mouse fetuses that have been stained with alizarin red S and cleared. Variation was determined for repeated measurements with each technique of the same specimen as well as the variation among specimens. There was variation in the results of direct measurements of the same specimens, but this was significantly (P less than 0.05) less than the variation among specimens, and the variation of measurements of the same specimen made using the photographic method was not significantly (P greater than 0.2) different from the variation among the specimens, and the variation of the specimens was not significantly (P greater than 0.2) different between the photographic and direct methods. Direct measurement is recommended for making linear measurements on the cleared skull. The photograph method allows better delineation of angles and calculation of surface area.

Animals↗
PubMed1988

Pattern of blood vessels in forelimbs of three strains of mice.

A technique was developed for visualizing the pattern of arteries in the adult mouse forelimb. The aorta was cannulated and injected with blue stained Batson's Number 17 Anatomic Compound to perfuse the forelimb arteries; the ossified skeleton was stained and the soft tissues were cleared, making it possible to examine the entire arterial system in the intact specimen. The pattern of distribution of arteries were compared in 120 forelimbs from three strains of mice, two inbred and one hybrid. Significant differences between the three strains were found for 9 of 16 variations evaluated. Differences in the point of origin of vessels were the most common; differences in the fusion of vessels, the extension of vessels and the presence of extra vessels were also identified. The patterns were much more constant in the two inbred strains than in the hybrid strain, suggesting the importance of genetic factors in determining the arterial pattern. Absence of major vessels and an abnormal persistence of embryonic vessels, which have been observed in association with skeletal malformations, were not observed in any of the 120 normal adult mouse forelimbs examined.

Animals↗
PubMed1987

Low fetal loss rates after ultrasound-proved viability in early pregnancy.

Once pregnancy is recognized clinically, it is accepted that 12% to 15% undergo spontaneous abortion. However, the actual time of fetal demise has not yet been determined. To address this question, the outcomes of pregnancies identified before 21 days of conception by serum beta-human chorionic gonadotropin assays were studied. All subjects underwent ultrasound examinations at eight and 12 weeks' gestation. Among 220 women who had a viable pregnancy at eight weeks, only seven (3.2%) experienced a fetal loss thereafter. The results of this study suggest that most clinically recognized spontaneous abortions manifested after eight weeks actually represent pregnancies in which fetal demise occurred before eight weeks. These findings have important implications with respect to the safety of chorionic villi sampling and to the identification of exogenous agents that cause fetal wastage.

Abortion, Spontaneous↗
PubMed1987

Unilateral carpal bone deformity in mother and son.

We report on a mother and son with unilateral absence of most of the proximal carpal bones, dysplasia of the distal row of carpal bones, and deformity of the forearm. Although carpal bone dysplasia has been reported in several congenital or progressive disorders, unilateral involvement with lack of progression makes this a distinct entity.

Abnormalities, Multiple↗