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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
PubMed1992

A case of agnathia, situs inversus, and a normal central nervous system.

We report here a premature female infant with agnathia, low-set but normally formed ears, a downward eye slant, choanal atresia and a cleft palate. She had severe respiratory distress and died despite maximum intervention at 5 days of age. Autopsy revealed situs inversus totalis; crossed fused renal ectopia; agnathia; normal thyroid, larynx, trachea, and bronchi; incomplete lobation of the lungs; immature pulmonary development with early hyaline membranes; and a normal central nervous system. This lack of significant central nervous system abnormalities distinguishes this infant from the majority of previously reported infants with agnathia and situs inversus.

Abnormalities, Multiple↗
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

Homeobox genes and congenital malformations.

In this review we have built a case for abnormal Hox gene expression in human congenital malformations without presenting any direct evidence of their involvement. This approach is justified by the dramatic advances in developmental genetics which emphasize the considerable similarity in the primary processes and molecules used to guide early morphogenesis in all species. Hox genes occupy a central role in this scheme, being activated in a specific rostral-caudal order after initial specification of the basic embryonic axes and, thereafter, specifying positional identity by influencing downstream "realizator" genes that carry out the position-specific program. These theoretical arguments, together with the dramatic results obtained in an evolutionarily similar organism (the mouse) using the transgenic and gene deletion approaches, make it highly likely that abnormalities in Hox gene structure and expression will soon be implicated in specific human congenital malformation syndromes. In parallel with this phenotypic analysis, we can expect that the animal models discussed in this review will provide greater detail regarding the upstream regulators and downstream targets of Hox gene products. Together these approaches promise to finally elucidate some of the underlying mechanisms responsible for human congenital malformations.

Animals↗
PubMed1991

Etiologic complexities of diaphragmatic defects: right diaphragmatic hernia, pulmonary hypoplasia/agenesis, and hydrocephalus in sibs.

Here we review the complexities of diaphragmatic defects and describe sibs with small, right diaphragmatic defects with pulmonary hypoplasia/agenesis and hydrocephalus. Despite a poor initial prognosis, the propositus has progressed remarkably well. Antenatal sonographic study detected hydrocephalus but not the diaphragmatic defect in the sib of the propositus. Because diaphragmatic defects are most commonly found in association with other anomalies and may occur in association with chromosome anomalies careful workup of all affected infants is crucial for accurate genetic counseling.

Abnormalities, Multiple↗
PubMed1991

Autosomal dominant sensorineural hearing loss. Pedigrees, audiologic findings, and temporal bone findings in two kindreds.

We report the clinical and otopathologic findings in three persons from two kindreds affected with adult-onset autosomal dominant progressive sensorineural hearing loss. The primary pathologic change is a deposit of acid polymucosaccharide ground substance in the cribrose areas; in the spiral ligament, limbus, and spinal lamina of the cochlea; and in the stroma of the maculae and cristae. These deposits obstruct the channels that accommodate the dendritic nerve fibers to the auditory and vestibular sense organs. The end result is strangulation and degeneration of dendrites followed by retrograde neuronal degeneration in association with varying degrees of atrophic change in the sense organs.

Adult↗
PubMed1990

Absence of need for amniocentesis in patients with elevated levels of maternal serum alpha-fetoprotein and normal ultrasonographic examinations.

BACKGROUND: Recent improvements in the accuracy of sonographic diagnosis of neural-tube and ventral-wall defects have raised a question about the wisdom of routinely offering amniocentesis to women who have elevated levels of maternal serum alpha-fetoprotein with a structurally normal fetus as determined by ultrasonography. METHODS: We reviewed the ultrasound findings in 51 consecutive fetuses with spina bifida, encephalocele, gastroschisis, or omphalocele that were delivered or aborted at a single hospital, to estimate the sensitivity of ultrasonography for these diagnoses. In all cases, the mothers had undergone prenatal sonography at one facility between 16 and 24 weeks after the last menstrual period. We used these data to calculate the probability of an affected fetus in a women with a given level of maternal serum alpha-fetoprotein and a normal sonogram. RESULTS: These four types of anomalies were correctly identified in all 51 cases, yielding a sensitivity of 100 percent (95 percent confidence interval, 94 to 100 percent). Using the lower limit of this confidence interval, we calculated that the probability of an affected fetus ranges from 0.01 to 0.15 percent for maternal serum alpha-fetoprotein levels ranging from 2.0 to 3.5 times the median, respectively. CONCLUSIONS: This level of risk is less than the reported risk of abortion due to amniocentesis and may lead some women with elevated levels of alpha-fetoprotein to decide not to proceed with amniocentesis.

Amniocentesis↗
PubMed1990

Hand-foot-genital syndrome: the importance of hallux varus.

The hand-foot-genital syndrome is an autosomal dominant disorder previously reported in six families. This report of the seventh family identified with this syndrome is presented to emphasize the frequent occurrence of medial deviation of the first toes (hallux varus).

Abnormalities, Multiple↗
PubMed1989

Malformations due to presumed spontaneous mutations in newborn infants.

We conducted hospital-based surveillance of congenital malformations to determine the rate of apparently spontaneous single mutations leading to recognized phenotypes. Through surveillance of 69,277 infants with gestational ages of at least 20 weeks, we identified 48 infants (0.07 percent) with major malformations, with phenotypes that suggested that the malformations were due to single mutant genes. Family studies suggested that 11 of these infants (10 with autosomal dominant disorders and 1 with an X-linked condition) were affected as the result of a new (spontaneous) genetic mutation. The spontaneous mutation rates per gene were 0.7 x 10(-5) and 1.44 x 10(-5) for the disorders in which one and two infants were affected, respectively. In addition, 5 of the 10 infants with autosomal recessive malformations had negative family histories, but we were unable to infer the presence of spontaneous mutations in these cases. Because the family history was negative in 44.4 percent of the infants with disorders considered due to autosomal or X-linked genes, counseling should include the understanding that genetic disorders often occur unexpectedly among children of healthy parents.

Congenital Abnormalities↗
PubMed1989

Diagnostic criteria for Walker-Warburg syndrome.

Walker-Warburg syndrome (WWS) is an autosomal recessive disorder manifest by characteristic brain and eye malformations. We reviewed data on 21 of our patients and an additional 42 patients from the literature. From this review, we expand the phenotype to include congenital muscular dystrophy (CMD) and cleft lip and/or palate (CLP), and revise the diagnostic criteria. Four abnormalities were present in all patients checked for these anomalies: type II lissencephaly (21/21), cerebellar malformation (20/20), retinal malformation (18/18), and CMD (14/14). We propose that these comprise necessary and sufficient diagnostic criteria for WWS. Two other frequently observed abnormalities, ventricular dilatation with or without hydrocephalus (20/21) and anterior chamber malformation (16/21), are helpful but not necessary diagnostic criteria because they were not constant. All other abnormalities occurred less frequently. Congenital macrocephaly with hydrocephalus (11/19) was more common than congenital microcephaly (3/19). Dandy-Walker malformation (10/19) was sometimes associated with posterior cephalocele (5/21). Additional abnormalities included slit-like ventricles (1/21), microphthalmia (8/21), ocular colobomas (3/15), congenital cataracts (7/20), genital anomalies in males (5/8), and CLP (4/21). Median survival in our series was 9 months. A related autosomal recessive disorder, Fukuyama congenital muscular dystrophy, consists of similar but less severe brain changes and CMD. It differs from WWS because of consistently less frequent and severe cerebellar and retinal abnormalities. We think that WWS is identical to "cerebro-oculo-muscular syndrome" and "muscle, eye, and brain disease."

Brain↗
PubMed1989

Acrocallosal syndrome: new findings.

We describe a 21-month-old girl with typical manifestations of the acrocallosal syndrome of craniofacial anomalies, agenesis of the corpus callosum, hallucal duplication, severe hypotonia, and psychomotor retardation. Our patient also had the Dandy-Walker malformation, imperforate anus with rectovaginal fistula, hypothalamic dysfunction with hypothyroidism and diabetes insipidus, thick, dysplastic pulmonic valve leaflets, central and obstructive apnea, and pulmonary hypertension. These findings add to the delineation of this syndrome.

Abnormalities, Multiple↗
PubMed1989

Pena-Shokeir phenotype in sibs with macrocephaly but without growth retardation.

A number of more or less distinct subgroups with the Pena-Shokeir phenotype have been identified. We studied two brothers with the Pena-Shokeir phenotype who were unusual because they had macrocephaly and normal growth. In the second sib, no neuromuscular abnormalities were found at autopsy. Among the subgroups with Pena-Shokeir phenotype, these sibs resemble the family reported by Ohlsson et al. [1988] more than the other subgroups that have been proposed. In addition, abnormalities were detected by prenatal ultrasonography during the 18th week of gestation of the second fetus. This finding provides additional evidence that this phenotype may be detected early enough in gestation to consider intervention.

Abnormalities, Multiple↗
PubMed1989

Drug ingestion during pregnancy: infrequent exposure in a contemporary United States sample. National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study Group.

Drug ingestion in a cohort of United States women proved consistently lower than in prior United States populations. Participating were 342 insulin-dependent diabetic and 387 control subjects who were enrolled before conception (76%) or no later than 21 days after conception (24%). Drug exposures were then recorded at entry and periodically throughout organogenesis (gestational weeks 6, 8, 10). During gestational weeks 1 to 10, approximately two thirds of the subjects were exposed to no agent other than oral iron, oral vitamins, or insulin (diabetic subjects). The mean exposures in gestational weeks 1 to 10 were 0.72 +/- 1.05 (SD) for diabetic women and 0.54 +/- 0.96 for control subjects; throughout pregnancy, the mean exposures were 1.26 +/- 1.66 and 1.58 +/- 1.78, respectively. The low exposure frequency in this contemporary United States population is highly encouraging. However, it follows that collaborative cohort efforts may be necessary in order to assess teratogenicity of drugs because relatively few women are now exposed.

Abnormalities, Drug-Induced↗
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↗