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Biomedical subjects

T H Shepard

Publications and source records attributed to T H Shepard.

At least 55 records · Page 3Linked to original sources
PubMed1989

Congenital heart disease among spontaneous abortuses and stillborn fetuses: prevalence and associations.

The prevalence, range, and associations of congenital heart disease (CHD) were studied among 400 spontaneous abortuses between 9 and 40 weeks' gestation. Fifty-two (13.0%) cases of CHD were detected. To minimize selection bias the specimens were grouped by external appearance and the prevalence expressed accordingly. CHD was detected in 21 (7.3%) of 289 externally normal and 31 (27.9%) of 111 externally abnormal fetuses. Ventricular septal defect (VSD) was the most frequent CHD found in isolation as well as in combination with extracardiac malformations. Seventy-five percent of isolated CHD was VSD. Forty (69.2%) of the 52 cases of CHD were associated with extracardiac malformations. Chromosomal syndromes were responsible for a minimum of 19.2% of the cases and suspected in up to 36.5%. The most frequent associations involved the musculoskeletal system, central nervous system, abdominal wall, and kidneys. In contrast, studies of liveborn infants have reported 70% of CHD as isolated defects, including many CHD infrequently seen among spontaneous abortuses. This suggests that fetuses with isolated CHD often survive to term, and CHD does not significantly affect the survival of the fetus in utero. Ventricular septum formation may be particularly susceptible to hemodynamic changes and may be indicative of an underlying pathologic condition that also leads to a spontaneous abortion.

Abnormalities, Multiple↗
PubMed1989

Human achondroplasia: defective mitochondrial oxidative energy metabolism may produce the pathophysiology.

A summary is presented of previous studies by other investigators of human achondroplasia and dyschondroplastic animal models. In addition, studies previously reported from our laboratories are discussed, and they demonstrate that defective oxidative energy metabolism is present in mitochondrial preparations from achondroplastic human subjects and rabbits (ac/ac) with chondrodystrophy. The results of the studies support the hypothesis discussed fully in the manuscript that a partial defect in mitochondrial oxidative metabolism in achondroplastic subjects is expressed specifically in the growth plates of the long bones because this tissue has the lowest oxygen tension of any bodily organ undergoing active proliferation, thus leading to the achondroplastic phenotype in humans and the ac/ac rabbit. In the ac/ac rabbit phosphorylation at the cytochrome c oxidase region (site III) of the terminal respiratory system was shown to be absent in mitochondrial preparations from the livers of newborn ac/ac rabbits. Normal-appearing littermates did not exhibit the defect. Studies of mitochondrial preparations from human skin fibroblasts (grown in tissue culture) from normal human subjects and subjects with homozygous achondroplasia demonstrated that concentrations of cytochrome a3 were decreased approximately 80% in preparations from homozygous achondroplastic cells. Levels of cytochrome a3 in heterozygous achondroplastic cells were intermediate between the levels in normal cells and homozygous achondroplastic cells demonstrating the effects of gene dosage. Determination of total heme a (as the pyridine hemochromogen) in the normal and achondroplastic preparations from human subjects showed that the observed decrease in concentration of cytochrome a3 in the achondroplastic preparations was due to an absence of cytochrome a3 and not to a change in its absorbancy (extinction coefficient).

Achondroplasia↗
PubMed1989

Long-bone growth in fetuses with Down syndrome.

Short stature is a well-recognized component of Down syndrome. The femur lengths of affected fetuses have been observed to be shorter than normal, with a ratio of actual to expected femur length of less than 0.91 indicating a high risk of trisomy. To further evaluate this finding we have determined the relationship between limb lengths and gestational age in 37 postmortem fetal specimens with trisomy 21. Control values were obtained from 174 normal fetuses. Measurements of the femur, tibia, fibula, humerus, radius, and ulna were made from roentgenograms or by direct measurement of the bone. Most measurements for each bone of the affected fetuses fell below the normal regression line for that bone, but only 3/37 femurs, 4/32 tibias, 5/32 fibulas, 9/32 humeri, 10/32 radii, and 7/32 ulnas fell more than 2 SDs below the mean. The ratios of actual to expected femur lengths were computed and six fetuses with Down syndrome (16.2%) had ratios less than 0.91. The bones of the extremities of fetuses with trisomy 21 are shorter than normal, but the differences are relatively small. The ratio of actual/expected femur lengths was a less efficient predictor of Down syndrome than were either maternal age or maternal serum alpha-fetoprotein tests. The upper extremity bones were shorter than normal more often than were the bones of the lower extremity, and this finding should be explored further in a prospective study.

Bone Development↗
PubMed1989

Unexplained second trimester oligohydramnios: a clinical-pathologic study.

The importance of oligohydramnios in the absence of fetal malformations has been recognized because of the associated high risk for adverse pregnancy outcome. Pathologic dissections were performed on four fresh fetuses whose mothers were identified by ultrasound as having oligohydramnios and had no clinical history or physical evidence of vaginal leakage of amniotic fluid. The fetuses were all normal except for hypoplasia of the lungs and varying degrees of Potter's facies. The kidneys were histologically normal but had increased weight. The more widespread use of ultrasound may have allowed us to detect an earlier stage of a previously present type of pregnancy failure.

Abortion, Induced↗
PubMed1989

Placental weights of normal and aneuploid early human fetuses.

Placental and body weights were plotted for 252 normal human fetuses less than 600 gm and mean regressions and 95% prediction intervals were calculated. Placentas from 62 aneuploid fetuses were compared to these standards. Placenta to body weight ratios from 34 trisomy-21 fetuses were not reduced but those from 15 trisomy-18 fetuses were generally decreased. One of 5 trisomy-13 ratios was below the prediction interval. Among 7 triploid fetuses the ratios were above the normal interval in 3 and below normal in 4. Three of the triploids that were below were associated with a karyotype of 69,XXX and did not have hydatidiform degeneration. All 4 placentas with hydatidiform changes were abnormally large. All of the 7 triploids had 3-4 syndactyly and 3 had hydrocephalus.

Aneuploidy↗
PubMed1989

Chromosomal abnormalities in fetuses with omphalocele. Significance of omphalocele contents.

Twenty-six consecutive fetuses with a sonographically detectable omphalocele and known karyotype were reviewed to identify risk factors that might be associated with chromosomal abnormalities. Risk factors that were analyzed included contents of the omphalocele sac, maternal age, fetal sex, sonographically detectable concurrent anomalies, and any major concurrent anomaly. Chromosomal abnormalities were found in 10 cases (38%) from trisomy 18 (n = 4), trisomy 13 (n = 4), trisomy 21 (n = 1), or 45, X (n = 1). The absence of liver from the omphalocele sac (intracorporeal liver) was strongly associated with an abnormal karyotype; chromosomal abnormalities were present in all 8 fetuses with an intracorporeal liver compared to 2 of 18 fetuses with an extracorporeal liver (p less than .0001, two-tailed Fisher exact test). Other risk factors that were statistically associated with chromosomal abnormalities included advanced maternal age (greater than or equal to 33 years, p = .03) and sonographically detectable concurrent malformations (p = .05). We conclude that sonographic findings can help determine the relative risk of chromosomal abnormalities in fetuses with omphalocele; abnormal karyotypes were significantly associated with the absence of liver from the omphalocele sac and sonographically detectable concurrent malformations in this series. Sonographers should also be aware that omphaloceles that contain bowel alone tend to be small and can be missed or mistaken for other abdominal wall defects (gastroschisis or umbilical hernia).

Adolescent↗
PubMed1988

Fetal rhombencephalon: normal US findings.

Using ultrasound (US), the authors examined 25 embryos that were 8-10 menstrual weeks old for gestational age and the presence of a small cystic structure (3-4 mm) in the posterior aspect of the cranium. This structure was seen in all embryos. The US images of an in vitro embryo at 8 weeks menstrual age were also evaluated for anatomic correlation. Analysis of these US images determined that the cystic structure was the open rhombencephalon or hindbrain. Follow-up US studies or postpartum clinical examinations of the 25 in utero embryos demonstrated no abnormal posterior cranial cystic structures or neurologic deficits. This first-trimester structure should be considered a normal finding, since it develops into the normally proportioned fourth ventricle after the 11th menstrual week.

Female↗
PubMed1988

Organ weight standards for human fetuses.

Five hundred fifty-eight fresh human embryos and fetuses were obtained from the universities of Washington and Michigan following spontaneous loss, elective termination, or neonatal death within 2 days of delivery. The body weights ranged from 1.5 to 1500 g. Each of these autopsied specimens was morphologically normal. Specimens from diabetic or hypertensive mothers were not included. Correlations between fetal body weight and weights of adrenal, brain, kidney, liver, lung, spleen, and thymus were established. For analysis, regression curves were calculated as quadratic equations of best fit by the weighted least squares. The relation of the weights of brain, heart, and liver to body weight appeared linear. The ratios of thymus, spleen, and kidney to body weight were nonlinear and gradually increased. The ratios of lung and adrenal weights to body weight were also nonlinear and gradually decreased. Ninety-five percent prediction intervals were generated for each of the eight organs using a computerized statistical package. The results compare closely with smaller studies in the literature.

Body Weight↗
PubMed1988

Normal length of the human fetal gastrointestinal tract.

Little information is available on the normal length of the gastrointestinal tract in fetuses or on factors that may affect its growth. To determine normal growth patterns of the fetal intestine, 58 fetuses received in the Central Laboratory for Human Embryology between January 1, 1987, and July 1, 1988, in which no abnormalities were noted on autopsy, were studied. The gastrointestinal tract was removed from the fetus en bloc from the esophagogastric junction to the pelvic floor and dissected. Measurements of stomach, small and large intestines, and appendix length were made and correlated with gestational age as determined by footlength. Overall growth of the gastrointestinal tract as well as that of each component was linear with respect to gestational age. In addition, five fetuses with omphalocele, 16 with cardiac malformations, and 20 with chromosomal abnormalities were studied. The total lengths of the gastrointestinal tracts in the first group were below the normal range in four of five fetuses. Those with cardiac defects had intestinal lengths below the mean, but the measurements were abnormal in only three. In both groups those fetuses with chromosomal abnormalities appeared to have shorter intestinal tracts than those with normal or unknown karyotypes. The gastrointestinal tracts of aneuploid fetuses fell within the normal range until approximately 20 weeks gestation, after which growth decreased. This growth failure may reflect the growth retardation seen in fetuses with chromosomal abnormalities.

Aneuploidy↗
PubMed1988

Rat whole embryo culture: an in vitro model for testing nitrous oxide teratogenicity.

The teratogenic effects of nitrous oxide (N2O) on postimplantation rat embryos were studied using a whole embryo culture system to separate the direct effects of N2O from those that are maternally mediated. A total of 100, 10-day-old rat embryos were cultured in either a control atmosphere (75% N2, 20% O2, and 5% CO2), or a N2O atmosphere (75% N2O, 20% O2, and 5% CO2). After 22 h of culture embryos were examined microscopically, and protein and DNA contents were determined. DNA content was significantly lower in the embryos exposed to N2O compared with the controls. Additionally, three malformed embryos and four embryos with left-sided tails were observed in the N2O group, whereas no abnormalities were observed in the control group. There were no differences in crown-rump length, somite numbers, limb bud index, and protein content between the two groups of embryos. The positive findings in this study indicate that whole embryo culture is useful for studying the mechanisms of N2O teratogenicity.

Abnormalities, Drug-Induced↗
PubMed1987

Aspirin and acetaminophen use by pregnant women and subsequent child IQ and attention decrements.

In a longitudinal prospective study of 1,529 women pregnant in 1974-1975, aspirin and acetaminophen were the two medications most frequently taken during the first half of pregnancy (46 and 41%, respectively). In a selected cohort of 421 offspring of these women, examined at 4 years of age, maternal aspirin use during the first half of pregnancy was significantly related to IQ and attention decrements in the exposed children. Multiple regression analyses were used to statistically adjust for a variety of potentially confounding factors including demographic characteristics, child characteristics, other exposures, and lifestyle/environmental variables. Continuous dose-response and step-function parameterizations of aspirin exposure were both statistically significant and not clearly distinguishable from each other. The estimated aspirin effect is significantly greater for girls than boys. Aspirin effects on offspring function were found in the absence of effects on physical size both at birth and at 4 years. Maternal acetaminophen use was not significantly related to child IQ or attention. As this exploratory research originated from observations of a data set gathered for other purposes, it would be desirable to have these findings replicated in other studies. Further follow-up of the children at a later age is planned.

Acetaminophen↗
PubMed1987

Fetal hydrocephalus: sonographic detection and clinical significance of associated anomalies.

Sixty-one cases of fetal hydrocephalus were reviewed to determine the accuracy and clinical significance of prenatal ultrasound (US) for detecting concurrent anomalies. Of 61 fetuses studied, 51 (84%) had one or more major central nervous system (CNS) malformations (38 fetuses with 39 anomalies) and/or extra-CNS anomalies (34 fetuses). Only ten (16%) fetuses had no concurrent anomaly. Anomalies of the CNS were correctly identified with US in 35 of 39 (90%) cases. Of 34 fetuses (56%) with extra-CNS anomalies, 27 had multiple anomalies. One or more extra-CNS abnormality was identified with US in 22 of the 27 (81%) fetuses with multiple anomalies but no anomalies were identified with US in the seven patients with an isolated anomaly. Fetal mortality was directly related to the presence of extra-CNS anomalies (P less than .01). Many important anomalies coexisting with fetal hydrocephalus can be identified with US. Furthermore, sonographic detection of extra-CNS malformations carries a poor prognosis and was associated with a uniformly fatal outcome in this series.

Abnormalities, Multiple↗
PubMed1986

Studies of human achondroplasia: oxidative metabolism in tissue culture cells.

Mitochondria prepared from the first growth of cells (fibroblasts) from skin biopsies from homozygous (but not heterozygous) achondroplastic human subjects were unable to carry out oxidative phosphorylation. However, successive crops of cells gained the ability to phosphorylate with normal P:O ratios with pyruvate-malate and succinate as substrates. Concentrations of cytochromes a + a3 were markedly and significantly lower in homogenates of homozygous achondroplastic tissue culture cells than in homogenates of normal cells. Levels of cytochromes a + a3 in the heterozygous achondroplastic cells were intermediate between the levels in normal cells and the homozygous achondroplastic cells. Activities of the mitochondrial oxidative systems (NADH, succinic and cytochrome oxidases) were not significantly lower in the achondroplastic cell preparations than in normal cell preparations under standard assay conditions (saturation levels of oxygen).

Achondroplasia↗
PubMed1986

Methacrylic acid as a teratogen in rat embryo culture.

Using day 10 rat embryos cultured in vitro, we have shown that methacrylic acid is teratogenic at concentrations ranging from 1.2 to 2.1 mM. At these concentrations, methacrylic acid produced concentration-dependent decreases in growth parameters, i.e., crown-rump length, number of somites, and embryo protein content. In addition, methacrylic acid exposure produced malformed embryos characterized primarily by abnormal neurulation. Less frequent abnormalities included hypoplasia of the prosencephalon, edema, malpositioned heart, abnormal flexion, and dilated otic vesicles. Accompanying these abnormalities was an underlying increase in methacrylic acid-induced cell death.

Acrylates↗