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Biomedical subjects

L B Holmes

Publications and source records attributed to L B Holmes.

At least 73 records · Page 4Linked to original sources
PubMed1995

Symmetrical terminal transverse limb defects: report of a twenty-week fetus.

A 20-week gestation hydropic Thai fetus is reported who had symmetrical absence of each hand and forefoot with persistence of digit-like nubbins on each limb. The histologic studies showed there was calcified acellular material in the digit-like nubbins, consistent with infarcted blood vessels, and cartilaginous structures that represented possibly the distal metacarpal articulating surface. The red blood cell indices of both parents were consistent with their being heterozygous for a hemoglobinopathy, such as alpha-thalassemia, which is common in Thais. The infarcted blood vessels could be the result of thrombosis of the digital arteries in the fetus due to a hemoglobinopathy such as hemoglobin Bart's, just as rabbit fetuses homozygous for brachydactyly have transverse terminal digit amputations following digital vessel occlusions due to macrocytic anemia. This was the only child with symmetrical absence of the hands and feet identified among 123,489 liveborn and stillborn infants surveyed for major malformations.

Female↗
PubMed1995

Phenytoin embryopathy: effect of epoxide hydrolase inhibitor on phenytoin exposure in utero in C57BL/6J mice.

Previous animal research has suggested that the phenytoin arene oxide metabolite is teratogenic in acute studies and that the fetal effects were increased after injecting an inhibitor of microsomal epoxide hydrolase (mEH) (Martz et al., Pharmacol Exp Ther 203:231-239, 1977, Barcellona et al., Teratog Carcinog Mutagen 7:159-168, 1987). We have studied the effects of chronic oral phenytoin exposure in utero and the mEH inhibitor trichloropropene oxide (TCPO) on the prenatal growth and development of an inbred mouse strain with a low incidence of spontaneous oral clefting (C57BL/6J). Chronic daily gastric gavage of phenytoin produced a plasma level (mean 10.7 micrograms/ml on gestation Day 8) within the range recommended to prevent epilepsy in humans; this did not produce an increase in oral clefting or ventricular septal defects in the exposed C57BL/6J pups. It did produce a significant delay in prenatal growth and development, including phalangeal ossification. However, except for percentage resorptions/implantation, there was no synergism between phenytoin and TCPO in contrast to the finding reported by Martz et al. in Swiss mice. This issue was also assessed in a test of the fetal effect of phenytoin injected with TCPO, as had been done by Martz et al. There were no oral clefts or ventricular septal defects or a difference (P > 0.05) in prenatal growth and development in these C57BL/6J pups compared to the chronic gastric phenytoin plus TCPO group. This suggests either that differences in the genotypes of Swiss and C57BL/6J mice may be a contributing factor or that other teratogenic mechanisms were involved.

Animals↗
PubMed1995

Possible fetal effects of cervical dilation and uterine curettage during the first trimester of pregnancy.

We describe two malformed infants whose mothers had cervical dilation and uterine curettage. One mother had the procedure at 8 weeks and the other at 6 weeks of gestation. One infant had a facial cleft, hypertelorism, scalp defects, brain malformations, and absent fingernails and a constricting band on the fourth and fifth fingers. The other infant had an area of diminished scalp hair, vertebral anomalies, and a heart defect.

Brain↗
PubMed1995

Absence/hypoplasia of tibia, polydactyly, retrocerebellar arachnoid cyst, and other anomalies: an autosomal recessive disorder.

Absence or hypoplasia of the tibia has been reported to occur as an isolated hereditary malformation as well as a feature of several autosomal recessive and autosomal dominant syndromes. We report three sibs with absence or hypoplasia of the tibia in association with other malformations whose parents are first cousins once removed. These infants appear to have a "new" autosomal recessive syndrome.

Abnormalities, Multiple↗
PubMed1995

Metabolic control and progression of retinopathy. The Diabetes in Early Pregnancy Study. National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study.

OBJECTIVE: To evaluate the role of metabolic control in the progression of diabetic retinopathy during pregnancy. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study of 155 diabetic women in the Diabetes in Early Pregnancy Study followed from the periconceptional period to 1 month postpartum. Fundus photographs were obtained shortly after conception (95% within 5 weeks of conception) and within 1 month postpartum. Glycosylated hemoglobin was measured weekly during the 1st trimester and monthly thereafter. RESULTS: In the 140 patients who did not have proliferative retinopathy at baseline, progression of retinopathy was seen in 10.3, 21.1, 18.8, and 54.8% of patients with no retinopathy, microaneurysms only, mild nonproliferative retinopathy, and moderate-to-severe nonproliferative retinopathy at baseline, respectively. Proliferative retinopathy developed in 6.3% with mild and 29% with moderate-to-severe baseline retinopathy. Elevated glycosylated hemoglobin at baseline and the magnitude of improvement of glucose control through week 14 were associated with a higher risk of progression of retinopathy (adjusted odds ratio for progression in those with glycohemoglobin > or = 6 SD above the control mean versus those within 2 SD was 2.7; 95% confidence interval was 1.1-7.2; P = 0.039). CONCLUSIONS: The risk for progression of diabetic retinopathy was increased by initial glycosylated hemoglobin elevations as low as 6 SD above the control mean. This increased risk may be due to suboptimal control itself or to the rapid improvement in metabolic control that occurred in early pregnancy. Excellent metabolic control before conception may be required to avoid this increase in risk. Those with moderate-to-severe retinopathy at conception need more careful ophthalmic monitoring, particularly if their diabetes was suboptimally controlled at conception.

Adult↗
PubMed1994

Lessons on objectivity in clinical studies.

Clinical assessments made with measuring devices are generally considered "objective" and "accurate" and are, therefore, more discriminating than subjective assessments. We show that the choice of measuring devices or non-standardized landmarks to be used with the measuring devices affect the "accuracy" of the "objective" findings.

Cephalometry↗
PubMed1994

Anticonvulsant teratogenesis: I. A study design for newborn infants.

The basis for the apparent teratogenicity of maternal epilepsy is controversial. Is the critical factor the anticonvulsant drugs taken by the pregnant woman, or the genes which cause the mother's epilepsy? We describe a study design developed to assess these competing theories in a cohort study of newborn infants. We show the feasibility of ascertaining exposed and unexposed infants at several birthing hospitals in one urban area. Between 1986 and 1988, we identified 180 drug-exposed and 218 epilepsy-history infants among 49,403 infants. The rate of exposure to seizure medication was 0.36% and of maternal history of epilepsy was 0.44%. A significant number of infants could not be evaluated because they were missed, ineligible, or either the doctor, nurse or parent refused to participate. Overall, there was a significant increase in major malformations, microcephaly or growth retardation among the drug-exposed infants in comparison to both the epilepsy-history and the unexposed infants. The types of epilepsy and the apparent etiology were the same among women who took anticonvulsants and women with a history of epilepsy but no anti-convulsants during pregnancy. This study must be extended to include a sufficient number of infants exposed to each commonly used drug as monotherapy to allow for a comparison of the effect of each drug on pregnancy outcomes; to provide a comparison of infants whose mothers had a strong family history of epilepsy with infants whose mothers had trauma-induced epilepsy; and to assess the possible impact of the severity of the mothers' disease on the infants.

Abnormalities, Drug-Induced↗
PubMed1994

Anticonvulsant teratogenesis: 2. Statistical methods for multiple birth outcomes.

The purpose of this paper is to demonstrate the application of generalized estimating equations to assess an exposure effect using multiple birth outcomes. This multivariate approach provides the flexibility of regression modeling and improved power, as compared to series of univariate analyses or collapsing the multiple end-points to a single indicator of affectedness. Motivating the discussion will be a large cohort study designed to assess the effects of anticonvulsant medications on a variety of birth outcomes, including major malformations, and growth and weight parameters, as well as a broad spectrum of minor physical anomalies. Because the study is still in progress, the aim here is not to present a definitive analysis, but to present and describe the application of these recently developed statistical methods to analyze studies with multiple outcomes. For simplicity, we will focus on the control and drug-exposed groups only from that study (ignoring the seizure history group), and we will concentrate on an analysis of minor physical anomalies.

Abnormalities, Drug-Induced↗
PubMed1994

Anencephaly: changes in prenatal detection and birth status, 1972 through 1990.

OBJECTIVE: We assessed at a large university hospital the effect of prenatal diagnosis on the birth of infants with anencephaly between 1972 and 1990. STUDY DESIGN: All 175 affected infants were identified by a postnatal Malformations Surveillance Program, which included stillborn infants and elective terminations in the second trimester. The affected infants were subdivided into those whose mothers had always planned delivery at this hospital (nontransfers) and those whose mothers had planned delivery elsewhere but were transferred after the prenatal detection of the fetal abnormality (transfers). RESULTS: In the 1970s half the infants were anencephaly were born alive; the average gestational age was 35.6 weeks, and only a few were diagnosed prenatally. By 1988 to 1990 all affected infants were diagnosed either by prenatal ultrasonography or as the result of maternal serum alpha-fetoprotein screening; the parents elected to terminate the pregnancies, and the average gestational age was 19.6 weeks. CONCLUSION: Prenatal detection and the selection by parents of the option of elective termination of pregnancy has altered significantly the birth status of infants with anencephaly since 1972.

Abortion, Induced↗
PubMed1994

Head circumferences standards in neonates.

Head circumference at birth is an important measure of intrauterine growth, reflecting accurately brain growth and predicting subsequent development. Standards need to reflect the population and the factors that affect intrauterine growth in the population and must be constructed in a manner that is clinically useful and predictive. Many of the present standards used to assess newborn infants are inadequate because of the limitations of sample size and study design. As a result, the current standards are not adequate for premature infants below 30 weeks of gestation and, in newborns from later in gestation, may underreport significant deviations from the mean in certain situations.

Cross-Cultural Comparison↗
PubMed1994

Spina bifida: anticonvulsants and other maternal influences.

At least two maternal conditions have been shown to be associated with an increased risk for the occurrence of anencephaly, spina bifida and encephalocele: insulin-dependent diabetes mellitus in the mother and maternal epilepsy for which anticonvulsant treatment is being used. Of 147 infants born at the Brigham and Women's Hospital with anencephaly, spina bifida and encephalocele among 123,489 live-born, still-born and elective terminations surveyed, 7.5% were infants of insulin-dependent diabetics and 0.7% had been exposed to anticonvulsants in utero. In addition to these proven causal associations neural tube defects have been postulated by some, but not all, studies as being more common among infants exposed to hyperthermia in utero and to drugs used to induce ovulation.

Anticonvulsants↗
PubMed1993

Moderate caffeine use and the risk of spontaneous abortion and intrauterine growth retardation.

OBJECTIVE: To examine the relationship between caffeine consumption during pregnancy and the occurrence of spontaneous abortion and intrauterine growth retardation. DESIGN, SETTING, AND PATIENTS: A cohort of 431 women, enrolled in a multicenter study within 21 days of conception, was monitored throughout pregnancy to determine (1) caffeine exposure, (2) exposure to other risk factors, (3) fetal growth as assessed by ultrasonography, and (4) pregnancy outcome. OUTCOME MEASURES: Spontaneous abortion, intrauterine growth, birth weight, and head circumference. RESULTS: The mean (+/- SD) first-trimester caffeine consumption was not significantly higher in women who aborted (125.9 +/- 123.1 mg) than in women who delivered liveborn infants (111.6 +/- 107.0 mg) (P = 34). The adjusted odds ratio (OR) for spontaneous abortion was 1.15 (95% confidence interval [CI], 0.89 to 1.49). Early fetal growth, assessed by crown-rump length on ultrasonographic examination, was not affected by caffeine. Although the group consuming the most caffeine (> 300 mg/d) had a significantly higher proportion of babies with birth weights and head circumferences below the 10th percentile in the crude analysis, the association with caffeine was no longer significant when other risk factors (notably smoking) were taken into account. The adjusted ORs were 1.11 (95% CI, 0.88 to 1.40) for decreased birth weight and 1.09 (95% CI, 0.86 to 1.37) for smaller head circumference. CONCLUSIONS: Close monitoring of a cohort identified very soon after conception enabled us to identify all abortions after 21 days postconception, monitor intrauterine growth prospectively, and track caffeine use. Despite this intensive surveillance, we found no evidence that moderate caffeine use increased the risk of spontaneous abortion, intrauterine growth retardation, or microcephaly after accounting for other risk factors.

Abortion, Spontaneous↗
PubMed1993

Report of National Institute of Child Health and Human Development Workshop on Chorionic Villus Sampling and Limb and Other Defects, October 20, 1992.

A Workshop on Chorionic Villus Sampling (CVS) was convened by the National Institute of Child Health and Human Development (NICHD) and the American College of Obstetricians and Gynecologists at the National Institutes of Health on April 17, 1992, to discuss recent reports of an increased occurrence of malformations of the upper and lower limbs and oral structures among CVS-exposed infants. We summarize here the defects described in the CVS-exposed infants, the retrospective reassessments of published studies of the safety of CVS, the prevalence of limb deficiencies in infants not exposed to CVS, the status of the 7-9 week (conception or fertilization age) embryo, and the relevant human and animal experimental models of how CVS might be harmful to the embryo or fetus.

Chorionic Villi Sampling↗
PubMed1993

A case of a closed partial cloacal septation defect with a patent urachus.

A boy with a closed partial cloacal septation defect with a patent urachus is reported. He had an intact abdominal wall, a patent urachus, a colovesical fistula, intact genitalia and urethra, imperforate anus, and a lipomyelocystocoele. Patients with similar constellation of findings have been reported as cloacal exstrophy variants. What distinguishes this case from the other reported variants is the intact abdominal wall with the patent urachus, the small and normally formed phallus and urethra, and the presence of a lipomyelocystocoele. We discuss the possible embryologic mechanism responsible for this boy's findings and possible relationship with the cloacal exstrophy spectrum. We also discuss new terminology for the epispadias-exstrophy spectrum. Furthermore this case reminds us that there is considerable variability within the epispadias-exstrophy spectrum.

Abnormalities, Multiple↗