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Biomedical subjects

L B Holmes

Publications and source records attributed to L B Holmes.

At least 19 recordsLinked to original sources
PubMed1995

Genetic heterogeneity of heart-hand syndromes.

BACKGROUND: Heart-hand syndromes compose a class of combined congenital cardiac and limb deformities. The proto-typical heart-hand disorder is Holt-Oram syndrome, which is characterized by cardiac septation defects and radial ray limb deformity. We have recently mapped the Holt-Oram syndrome gene defect to the long arm of human chromosome 12 in two families. The role of this disease locus in the pathogenesis of related conditions such as heart-hand syndrome type III (cardiac conduction disease accompanied by skeletal malformations) or familial atrial septal defects is unknown. METHODS AND RESULTS: Clinical evaluations and genetic linkage analyses were performed in five additional kindreds with Holt-Oram syndrome and also in one kindred with heart-hand syndrome type III and one kindred with familial atrial septal defect and conduction disease. Holt-Oram syndrome in all five kindreds mapped to chromosome 12q2. These studies and previous data provide odds of greater than 10(25):1 that the Holt-Oram syndrome disease gene is at chromosome 12q2. In contrast, neither the phenotypically similar disorder heart-hand syndrome type III nor the locus responsible for a familial atrial septal defect with atrioventricular block maps to chromosome 12q2. CONCLUSIONS: We demonstrate that heart-hand syndromes are genetically heterogeneous. Conditions that clinically appear to be partial phenocopies of Holt-Oram syndrome arise from distinct disease genes.

Chromosomes, Human, Pair 12↗
PubMed1995

Genital abnormalities in females with Bardet-Biedl syndrome.

The major manifestations of the Bardet-Biedl syndrome are digital anomalies, tapetoretinal degeneration, obesity, renal abnormalities, and hypogenitalism (described mainly in males). We report on 2 girls with Bardet-Biedl syndrome who also had vaginal atresia. A similar association in females with Bardet-Biedl syndrome was suggested in published reports of 11 affected individuals who had structural genital abnormalities, (some of which were missed in childhood), including persistent urogenital sinus, ectopic urethra, hypoplasia of the uterus, ovaries and fallopian tubes, uterus duplex, and septate vagina. The association of atresia of the vagina and other malformations of female genital structures in individuals with Bardet-Biedl syndrome has often been missed in childhood and should be looked for more systematically.

Child↗
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

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↗
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↗