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Biomedical subjects

E B Hook

Publications and source records attributed to E B Hook.

At least 91 records · Page 5Linked to original sources
PubMed1990

Chromosome abnormalities in older women by maternal age: evaluation of regression-derived rates in chorionic villus biopsy specimens.

Maternal age-specific rates of chromosome abnormalities in women undergoing chorionic villus sampling (CVS) were evaluated. These were rates derived from regression equations of the form rate = ln(b[age] + c) where age varied from 35 to 48 years; and b and c are parameters. For Down syndrome (47, + 21), b = 0.29 and c = -15.53; for other nonmosaic abnormalities, b = 0.25 and c = -14.11; and, for all abnormalities, b = 0.27 and c = -14.22. The predicted rates per 1,000 varied, respectively, from 4.2, 4.6, and 8.8 at age 35 years to 180.0, 120.0, and 300.0 at age 48 years. The predicted numbers of abnormalities were compared with those observed in an overlapping data set reported in the literature. For 47, + 21, the ratio of observed (O) to expected (E) numbers was 54/56.4 = 0.96, suggesting that these rates are at least not grossly erroneous. For non-47, + 21 chromosome abnormalities, the ratio of O to E was 66/51.1 = 1.29. The possibility of geographic variation in rates of non-47, + 21 chromosome abnormalities cannot be dismissed. Finally, if 1) the regression derived rates are correct, 2) there is no difference in selective loss of chromosome abnormalities between younger and older mothers, and 3) the ratio of rates at ages 35 and 40 years to those in the women of all ages are the same for all abnormalities at CVS as for 47, + 21 in live births, then the proportion of all women with viable conceptuses at time of CVS who have an embryo or fetus with cytogenetic abnormality is 3.8-4.4 per 1,000 conceptuses.

Adult↗
PubMed1990

Timely monthly surveillance of birth prevalence rates of congenital malformations and genetic disorders ascertained by registries or other systematic data bases.

In many jurisdictions large data sets on malformations are now collected routinely in order to define prevalence rates of malformations in infants and children, to detect long-term secular trends, and to ascertain cases for ad hoc case-control studies. With slight modifications, these data sets may be used for prompt surveillance of changes in the birth prevalence of malformations, changes that conceivably could be possibly due to the introduction of a teratogen into the environment. A specific logistic approach is suggested, modeled on the New York State Malformation Registry, for prompt detection of changes in rates.

Cohort Studies↗
PubMed1989

Risks of unbalanced progeny at amniocentesis to carriers of chromosome rearrangements: data from United States and Canadian laboratories.

Data on 1,237 prenatal (amniocyte) diagnoses in cases of familial chromosome rearrangements were collated from 79 American and Canadian laboratories. These were added to European data (Daniel et al: Prenatal Diagn 6:315-350, 1986) on 596 reciprocal translocations (rcp) from 71 collaborative laboratories. The total data set was examined for relationships between balanced or unbalanced result and mode of ascertainment, sex of carrier parent, chromosomes involved, and (in cases of reciprocal translocations and pericentric inversions) for potential or actual chromosome imbalance size (% haploid autosome length). Risk rates for unbalanced segregants were markedly dissimilar. These ranged from approximately 50% down to essentially a negligible risk. The risk was approximately 50% for carriers of the following: complex chromosome rearrangements (ccr); insertions (ins); and for 2:2 segregating rcp ascertained by mode 1 (term unbalanced proband) with small imbalance segments. Pooled carriers (either sex) of 2:2 segregating rcp of mode 1 had a risk of 20-25% whereas female Robertsonian (rob) translocation (D;21) carriers and pericentric inversion (pii) carriers of pii with small distal segments had a risk of 10-15%. Pooled 2:2 segregating rcp carriers ascertained by mode 2 (a couple with recurrent miscarriages) and male carriers of rob (D;21) had a risk of 1.5-5%. The risk of unbalanced segregants was 1-2% (in this data) for male and female rob (13;14) carriers and for pooled pericentric inversion carriers. However, for carriers of most "type" (recurrent breakpoints) pii, for all paracentric inversions, and (as expected) for rob not involving 13 or 21, there were no term unbalanced progeny. For 2:2 segregating reciprocal translocations plots were prepared that could be used to determine broad risk groups for carriers of such rcp. In 3:1 segregating rcp there were 3.3 times fewer male than female carriers, whereas there were 1.3 times fewer male carriers in 2:2 segregating rcp. In 2:2 segregating rcp there is little effect on the fertility of male carriers and risks of unbalanced progeny were found to be equal to those for female carriers, whereas in the 3:1 segregating rcp, risks were much less for male as compared to female carriers. This indicates that 3:1 segregating rep are more similar to Robertsonian translocations in their greater effect on the fertility of male carriers.(ABSTRACT TRUNCATED AT 400 WORDS)

Abortion, Habitual↗
PubMed1989

How much difference does chromosome banding make? Adjustments in prevalence and mutation rates of human structural cytogenetic abnormalities.

A collaborative analysis was undertaken of 226 karyotypes with structural chromosome abnormalities diagnosed primarily with low level banding resolution, about 300 to 400 bands per karyotype. We estimate that in this series, use of low level banding was required to detect about 78% of pericentric inversions, about 51% of reciprocal translocations, about 47% of all balanced translocations, about 35% of unbalanced rearrangements other than rings, Robertsonian translocations and extra structurally abnormal chromosomes, about 11% of all unbalanced rearrangements, and about 35% of all structural abnormalities. Adjustment factors derived from these figures were applied to prevalence and mutation rates of structural mutation rates derived from published large scale studies of livebirths. Had low level banding been used in these earlier studies we estimate that the rate of all structural abnormalities would have been about 60% higher than those reported (3.8 per 1000 vs. 2.3 per 1000 in the original studies). The increase is much higher for balanced abnormalities, 75% (3.4 per 1000 vs. 1.9 per 1000), than for unbalanced abnormalities, 5% (0.42 per 1000 vs. 0.405 per 1000). The increase in mutation rates for de novo cytogenetic abnormalities was similarly, considerably higher after such adjustment: the rates per 100,000 gametes increased from 18.0 to 35.0 for balanced rearrangements, from 8.2 to 10.1 for unbalanced abnormalities and from 26.2 to 45.1 for all abnormalities. These estimates illustrate the difference even low level banding makes to detection of structural cytogenetic abnormalities and why contemporary studies using such methods cannot be compared with earlier large scale population studies or livebirths without some type of adjustment such as those suggested here.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Rate↗
PubMed1989

The natural history of cytogenetically abnormal fetuses detected at midtrimester amniocentesis which are not terminated electively: new data and estimates of the excess and relative risk of late fetal death associated with 47,+21 and some other abnormal karyotypes.

We report the results of an ongoing survey of rates of spontaneous death of fetuses with chromosome abnormalities detected at second-trimester amniocentesis in which the mother did not elect abortion. Estimated excess risks (and conservative 90% confidence intervals) of spontaneous fetal death for various cytogenetic abnormalities are as follows: 47,+21, 25.6% (18.0%-34.0%); 47,+18, 63.8% (49.3%-79.8%); 47,+13, 36.5% (11%-69.7%); 45,X, 65.3% (41.0%-84.2%); and mosaic 45,X/46,XX, 10.8% (1.0%-26.8%). There is little evidence for an excess risk of fetal death, at least following amniocentesis, for 47,XXX, 47,XXY, or 47,XYY. The excess risks of fetal death were adjusted for the likelihood that a fetus of normal karyotype would undergo spontaneous fetal death in a population of older maternal age similar to that in which prenatal cytogenetic diagnosis is undertaken. The absolute fetal death rates when this factor is ignored are about 3.5% higher (i.e., may be derived by adding 3.5% to the values given). The excess risks are those which are most appropriate for use in estimating the contribution of chromosome abnormalities to spontaneous fetal death.

Adult↗
PubMed1988

Evaluation of a temporal increase in ventricular septal defects: estimated prevalence and severity in northeastern New York, 1970-1983.

A marked increase or "epidemic" in ventricular septal defects (VSD) in recent years has been reported by the Center for Disease Control. Many pediatric cardiologists believe that this increase is simply a reflection of more intensive diagnosis and evaluation of infants throughout the country. Yet to our knowledge there has been no objective evidence for this explanation. We evaluated this possibility by considering records on live births occurring in 1970-1983 in the counties surrounding Albany, New York. In that period a single group of pediatric cardiologists has been evaluating all infants with suspected or confirmed cardiac defects in this area. We limited this analysis to ventricular septal defects unassociated with any cardiac syndrome complex. Thus, VSDs occurring as part of cyanotic heart disease or other complex cardiac "syndromes" were excluded. Consistent with the reported national trend, the estimated prevalence rate of ventricular septal defects diagnosed under 1 year of age in this period has increased from 1.0 per 1,000 live births in 1970 to 4.0 per 1,000 in 1983.(ABSTRACT TRUNCATED AT 250 WORDS)

Demography↗
PubMed1988

Variability in predicted rates of Down syndrome associated with elevated maternal serum alpha-fetoprotein levels in older women.

Quantitative predictions of rates of Down syndrome offspring as a function of maternal serum alpha-fetoprotein (MSAFP) values and of maternal age were reviewed. Comparisons were made of 35-year-equivalent-risk values by maternal age, that is, MSAFP values (at various maternal ages) that predict the risk (of a Down syndrome offspring) equivalent to that of an average 35-year-old woman irrespective of knowledge of MSAFP. This boundary was chosen because MSAFP values that predict a greater risk than this point for younger women or a lower risk for older women are likely in many jurisdictions to alter a decision about amniocentesis that would be reached without knowledge of MSAFP. There were marked differences among available studies in these 35-year-equivalent-risk values for older women. For instance, for age 41, the values among studies vary from 1.5 MoM to 2.1 MoM and the predicted proportion of 41-year-old women likely to be affected clinically by MSAFP determinations by the above criterion is 4.4%-18%, depending on which rate schedule is used. At age 39, the variation is 1.1 to 1.9 MoM or 7.1% to 38%. Possible explanations for the variation include sampling fluctuation. Relatively few data on Down syndrome have been used to calculate the parameters of the gaussian distributions used by the studies reviewed. It is suggested that great caution be used before employing published rate schedules for genetic counseling of older women, at least until sufficient data are collected and the nature of the discrepancies among studies is clarified.

Adult↗
PubMed1988

Maternal cigarette smoking, Down syndrome in live births, and infant race.

Previous studies have suggested that maternal smoking is negatively associated with a Down syndrome live birth. We analyzed the data of the U.S. Perinatal Collaborative Study in a search for racial variation in Down syndrome risk factors. There were 22 cases in 25,346 live births to smoking mothers (4/10,780 blacks, 18/13,320 whites, and 0/1,246 other races) and 42/29,130 live births to nonsmoking mothers (24/14,665 blacks, 14/11,694 whites, and 4/2,771 others). The crude overall rates per 1,000 live births were 0.4 in black smokers and 1.6 in black nonsmokers but 1.4 in white smokers and 1.2 in white non-smokers. Adjusted for maternal age, the summary relative risk for a Down syndrome live birth to a smoking mother was 0.2 in blacks (95% interval 0.1-0.7) but 1.2 in whites (95% interval 0.6-2.5). Stratification on variables associated with socioeconomic status or gestational age at time of entry into the study did not alter the racial difference. A comparison of smokers with those who never smoked revealed essentially the same trends. Among all nonsmokers the ratio of the maternal age-adjusted risks for a Down syndrome live birth in whites compared with blacks was 0.7 (95% interval 0.3-1.3), and among all smokers this ratio was 3.6 (95% interval 1.3-9.9). If the results are not attributable to statistical fluctuation or undetected confounding, then differences in the probability of intrauterine survival of the Down syndrome fetus would appear to be one plausible explanation for the difference.

Adolescent↗
PubMed1988

Maternal age-specific rates of 47,+21 and other cytogenetic abnormalities diagnosed in the first trimester of pregnancy in chorionic villus biopsy specimens: comparison with rates expected from observations at amniocentesis.

Results are presented on chromosome analyses made on 4,481 embryos or fetuses studied through chorionic villus sampling (CVS) in whom there was no known bias to presence of a chromosome abnormality except advanced parental age. We excluded from the analysis most cases in which mosaicism was diagnosed or in which there were cytogenetic discrepancies among samples obtained from the conceptus. There remain 48 cases of 47,+21, 39 cases of other nonlethal abnormalities, and 12 lethal abnormalities diagnosed in 4,481 studied. A regression analysis (restricted to the 3,848 cases diagnosed in the 35-49-year maternal age interval) was done on rates of (1) 47,+21, (2) other abnormalities excluding lethals or (3) including them, and (4) all abnormalities excluding lethals or (5) including them. The model used was y = exp(bx + c), where y is the rate of abnormality, x is maternal age at time of CVS (the modal age of the procedure was 10 gestational weeks from the last menstrual period), and b and c were, respectively, (1) 0.288 and -15.527; (2) 0.272 and -15.173; (3) 0.253 and -14.141; (4) 0.282 and -14.753; and (5) 0.271 and -14.195. We also derived rates of abnormalities at the time of CVS that would be predicted from rates (of nonmosaics) at amniocentesis after adjustment for the difference in gestational age between the usual times that these two procedures are done. The difference between the numbers of abnormalities predicted on the basis of these adjusted amniocentesis rates and the numbers observed at CVS provides an estimate of the spontaneous loss of embryos and fetuses between the usual gestational ages of these procedures. In these data, for 47,+21 the estimated proportion lost is 21% but the result is not significant at the .05 level. For other abnormalities excluding lethals the estimated spontaneous loss is 29% (P approximately .05); including lethals it is 44%. For all abnormalities, excluding lethals, pooled together, the estimate is 24%; including lethals it is 33%. The last three values are all significant at the .05 level or lower. The observed rates of abnormalities at CVS would be approximately 10% to 15% higher if one pooled diagnosed mosaics with the nonmosaics, but the estimated proportion of spontaneous fetal loss would be lower.

Adult↗
PubMed1987

Shakespeare, genetics, malformations, and the Wars of the Roses: hereditary themes in Henry VI and Richard III.

The four plays in the Henry VI-Richard III sequence well illustrate Shakespeare's recognition of hereditary influences upon the human condition. The inheritance of physical characteristics as manifest particularly by resemblance between fathers and sons is noted frequently. The absence of such resemblance is cited occasionally as evidence of illegitimacy. Personality traits are also viewed as inherited, although less consistently and there are important exceptions. Physical and mental traits when not derived from parents are ascribed to "nature" in the sense in which the term is often used today. Such traits are seen as being congenital or inborn even if not obviously "hereditary." Important exceptions to this are provided by the characters of the two lead characters in the play sequence. The weak-willed Henry VI is markedly different from his father, grandfather, and son who were all valiant, warlike, and brave. Shakespeare never explains this abrupt difference among generations. And the source of the evil character of Richard III is somewhat ambiguous. It seems most likely that in the first three plays of the sequence Shakespeare intended Richard's villainousness to be perceived as innate, caused by the same forces of nature that produced Richard's deformities (which are not further explained). But when Shakespeare wrote Richard III and gave more conscious consideration to what was now his central character he invoked an "environmentalist" explanation. Richard now is presented, albeit somewhat inconsistently, as evil in response to social ostracism because of his ugly deformities. This rather modern interpretation of the social origins of the personality of the deformed is particularly striking because it goes beyond anything in Shakespeare's historical sources, although Francis Bacon, a contemporary of Shakespeare, also recognized the effect of social forces upon the personality of the deformed.

Congenital Abnormalities↗