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Biomedical subjects

L B Holmes

Publications and source records attributed to L B Holmes.

At least 127 records · Page 7Linked to original sources
PubMed1987

Predictive value of minor anomalies: II. Use in cohort studies to identify teratogens.

Cohort studies of putative human teratogens can identify the full spectrum of phenotypic effects, including both major malformations and minor anomalies. Cohort studies which include the much more common minor anomalies make it possible to use a relatively small number of exposed and unexposed infants to identify an increase in the frequency of malformations. We evaluated this use of minor anomalies in a cohort study of newborn infants who had been exposed in utero to three putative teratogens: insulin-dependent diabetes mellitus in the mother and the use of the anticonvulsant phenytoin and exogenous sex hormones by the mother. In addition, the reproducibility of identifying minor anomalies was tested by comparing the results of examinations by two independent observers of 444 unexposed infants. The frequency of minor anomalies was increased among infants of diabetic mothers. However, the reproducibility of identifying minor anomalies was poor. We conclude that the examination of teratogen-exposed infants for minor anomalies cannot be used in epidemiologic studies of putative teratogens unless special efforts are made to maximize consistency in the identification of these features.

Abnormalities, Drug-Induced↗
PubMed1987

Predictive value of minor anomalies. I. Association with major malformations.

We examined 4305 white newborn infants for 114 minor physical features and major malformations to evaluate the hypothesis that the presence of three or more minor anomalies is highly predictive of a major malformation. We confirmed that the infant with three or more minor anomalies is at increased risk for a major malformation. However, this risk (19.6%) was much lower than the risk of 90% popularized by Smith and based on the study of Marden et al. (J Pediatr 1964;64:357). Analysis of the findings in the two studies showed that the lower predictive value was probably related to differences in study design. Nevertheless, some minor anomalies remain essential to the early recognition of several serious malformation syndromes.

Abnormalities, Multiple↗
PubMed1987

Verification of early pregnancy tests in a multicenter trial.

Tests for the diagnosis of early pregnancy have been available since 1974. However, no studies have systematically verified the accuracy of routine clinical laboratories in measuring human chorionic gonadotropin (hCG) prior to the time that pregnancy is clinically evident. We have conducted such a study in association with the NICHD-funded Diabetes in Early Pregnancy Study (DIEP). The purpose of this study was to elucidate the etiology of malformations in pregnancies complicated by diabetes mellitus, which probably occurs within the first few weeks of pregnancy, and therefore uniformity of pregnancy testing was necessary among the five centers to find an association of a teratogen at the time of organogenesis. We confirmed that routine clinical laboratories, in fact, could measure accurately hCG at the time of the missed menses; however, detection was not necessarily possible prior to that time. We conclude that in order to assure accurate diagnosis of early pregnancy, tests should ordinarily be delayed until time of the missed menses. When the test is used at this time, it is a reliable tool for early pregnancy testing and thus can be used to resolve questions relating to early pregnancy pathophysiology.

Chorionic Gonadotropin↗
PubMed1986

Kartagener's syndrome. A blinded, controlled study of cilia ultrastructure.

We investigated respiratory mucosa cilia ultrastructure in patients homozygous for the gene for Kartagener's syndrome (KS) and patients apparently phenotypic for KS who had bronchiectasis and sinusitis but without situs inversus. Parents, as obligate carriers of the recessive KS gene, were also evaluated among other control groups. The four patients with KS had significantly fewer cilia outer dynein arms than normal subjects or parents of patients with KS. Two of five patients apparently phenotypic for KS demonstrated distinctive ultrastructural changes. No other subjects demonstrated explicit ultrastructural abnormalities. Internal control specimens showed that the number of outer dynein arms was consistent within a subject compared with variation between subjects. The outer dynein arm serves as a dependable ultrastructural marker. Carriers of KS do not demonstrate distinctive morphologic cilia abnormalities. Not every patient with chronic bronchiectasis and sinusitis demonstrates abnormal cilia ultrastructure.

Adolescent↗
PubMed1986

Identification of Dh/+ and Dh/Dh embryos through close linkage of Dh and peptidase-3.

The close linkage between the genes Dominant hemimelia (Dh) and peptidase-3 (Pep-3) has been determined in 65 informative matings with the recombination frequency of 3.8%. Progeny testing showed that nonpenetrance does occur in Dh/+ adults. The presence of the "slow" and "fast" variants of Pep-3 can be determined in homogenates of kidney tissue as well as in a portion of the day 10 and 11 embryos. In a litter of embryos born to an informative mating, those which are Dh/Dh, Dh/+, and +/+ can be distinguished by the presence of the Pep-3 allele known to be in coupling with the Dh gene. This technique makes it possible to identify and to study the limb malformations and other phenotypic effects of Dh during their development and before the limb deformity is visible.

Alleles↗
PubMed1986

Complexities of intraventricular abnormalities.

We identified 59 fetuses and infants with intracranial anomalies over 5 1/2 years. The cases represented heterogeneous diagnostic groups: hydrocephalus with a neural tube defect, hydrocephalus with a specified structural anomaly, hydrocephalus of unspecified or miscellaneous cause, holoprosencephaly, and hydranencephaly. One or more major nonneural tube malformations were present in 19 of 54 cases. Eight of 32 cases had a significant chromosomal abnormality. The rate of survival was poor: 13 of 59 pregnancies were terminated electively before 24 weeks gestation, 10 of 59 infants were stillborn, and 16 of the remaining 38 liveborn infants have died since birth. A prenatal ultrasonographic diagnosis was made in the majority of cases (50 of 59). Diagnostic accuracy of prenatal ultrasound examinations ranged from a high of 90% for hydrocephalus to 33% for holoprosencephaly and hydranencephaly, and a low of 22% for the presence of extracranial malformations. Eleven cases in this series could have been considered potential candidates for in utero treatment of ventriculomegaly; this therapy would have been ineffective or inappropriate in eight of these. We recommend that each case undergo thorough diagnostic evaluation, including ultrasound examination and chromosome studies; that parents be informed of the high frequency of associated anomalies, the poor prognosis regarding survival, and the current limitations of ultrasound diagnostic accuracy; and that in utero treatment of fetal ventriculomegaly seems inadvisable at the present time.

Abortion, Induced↗
PubMed1985

Oto-palato-digital syndrome, type II--an X-linked skeletal dysplasia.

We report on two male infants with a lethal skeletal dysplasia characterized by cleft palate, midface hypoplasia, downward-slanting palpebral fissures, small thorax, and bowed limbs with absent fibulae. The clinical and radiographic changes are similar to those seen in the recently proposed oto-palato-digital syndrome, type II [Fitch et al, 1983]. The disorder is X-linked with heterozygous females being more mildly affected.

Bone Diseases, Developmental↗
PubMed1984

Familial nature of congenital absence and severe dysgenesis of both kidneys.

Seventy-one parents and 40 siblings of 41 index patients with bilateral renal agenesis, bilateral severe dysgenesis, or agenesis of one kidney and dysgenesis of the other were evaluated by gray-scale ultrasonography for genitourinary malformations. Nine per cent (10 of 111) had asymptomatic renal malformations, most often unilateral renal agenesis (4.5 per cent--a frequency that was significantly higher than the frequency of 0.3 per cent among 682 adults [P less than 0.004]). We recommend ultrasonographic screening for parents and siblings of infants born with agenesis or dysgenesis of both kidneys or with agenesis of one kidney and dysgenesis of the other, since renal malformations may have medical implications even for asymptomatic patients.

Abnormalities, Multiple↗
PubMed1984

Brief clinical report: an X-linked mental retardation syndrome with craniofacial abnormalities, microcephaly and club foot.

A male infant, who died of renal insufficiency at 6 months, had 2 similarly affected maternal uncles who died at 16 and 6 months respectively. Their manifestations include microcephaly, a large anterior fontanel, short nose with anteverted nostrils, club foot deformity, retarded psychomotor development and, in the index case only, kidney hypoplasia and dysplasia. The 2 obligatory carriers of this evidently X-linked recessive syndrome had no physical abnormalities.

Abnormalities, Multiple↗
PubMed1984

Natal and neonatal teeth: a clinical study.

In a survey of 18,155 infants, 7,155 of whom were examined personally, the prevalence of natal teeth was one in 716 for the infants examined and one in 3,667 for those surveyed. Another group of 38 infants and children with 61 natal and neonatal teeth were examined prospectively. All were mandibular central incisors. Sixty-one percent of the subjects had a pair of natal or neonatal teeth (or both). Ninety-five percent of the natal and neonatal teeth were normal primary central incisors, and 5% were supernumerary primary central incisors. Initially, in 31% of the teeth, enamel dysplasia was seen, the occurrence of which correlated with the duration of the gingival covering. It is recommended that natal and neonatal teeth be left in place, if possible, and removed only if they are extremely mobile, such that reattachment is unlikely.

Age Factors↗
PubMed1984

Effect of in utero exposure to anticonvulsants on craniofacial development and growth.

It has been widely reported that some children exposed to anticonvulsants in utero have a characteristic pattern of craniofacial anomalies including a broad, low nasal bridge with a short upturned nose, wide mouth, low set ears, epicanthal folds, and ocular hypertelorism, while others show no evidence of craniofacial abnormalities. The purpose of this paper is to define the craniofacial features in nine exposed children using anthropometric measurements and frontal and lateral cephalometric radiographs. These children were identified at birth as part of a prospective study of infants exposed to anticonvulsants at the Boston Hospital for Women (now part of the Brigham and Women's Hospital). At birth, none of these infants had any major malformations; at 4 to 10 years of age, none demonstrated any growth deficiency or mental deficiency, and all external craniofacial measurements were within the normal range. However, cephalometric analyses demonstrated a pattern of reduced bony interorbital distance, maxillary size, mandibular length, cranial base and skull size, and a reduction in nose dimensions when compared to data of normal populations. This study demonstrates the inadequacy of external measurements in determining the details of underlying craniofacial architecture. The data also suggest that a subtle craniofacial change occurs in exposed children which is characterized by a decrease in bony interorbital distance and the size of the cranial base and maxilla with concomitant decreases in nose and mandibular dimensions.

Abnormalities, Drug-Induced↗