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Biomedical subjects

E O'Brien

Publications and source records attributed to E O'Brien.

At least 73 records · Page 4Linked to original sources
PubMed1988

Inbreeding and genetic disease in Sottunga, Finland.

The contribution of inbreeding to the prevalence of recessive genetic diseases in the Aland Island parish of Sottunga is investigated. Genealogical data for 3,030 individuals spanning up to 15 generations were used to estimate inbreeding. This small island community shows a low average inbreeding value of .0031 for the period 1725-1975. A cohort analysis shows that inbreeding increased from 1750 to 1900, when maximum inbreeding for those born in Sottunga reached .0057. A sharp decline in inbreeding occurred thereafter. Individuals with island-born parents made the largest contributions to inbreeding in all time periods compared to those with one or two migrant parents. These trends are consistent with changing migration patterns and isolate breakdown in Aland since 1900. An analysis of pedigree development demonstrates that remote consanguinity contributed more to inbreeding through time than close consanguinity. Both the number of common ancestors and the number of paths of relationship between spouses increased dramatically through time, the latter at a much faster rate. The contribution to average inbreeding per path, however, diminished rapidly through time. This analysis indicates that inbreeding does not account for the high incidence of autosomal recessive disorders, such as tapetoretinal disease, found in the parish.

Consanguinity↗
PubMed1988

Founder effect and genetic disease in Sottunga, Finland.

Pedigree data are analyzed in order to determine the factors responsible for the high frequencies of certain genetic disorders in an isolated Swedish-speaking population of Finland's A land archipelago. The founders of Sottunga are identified, and the genetic contributions of each founder to descending birth cohorts are estimated. Founders born before 1700 have far more descendants in the contemporary gene pool than do more recent founders. However, because of migration and depopulation since 1900, the expected genetic contributions of the early founders to the present-day population are similar to those of later founders. A descendant in the contemporary population has a 2% chance of having inherited a particular gene from the founder who makes the largest single contribution to the gene pool. This corresponds approximately to a 2% probability of inheriting an autosomal dominant disease gene from this founder. Given an average inbreeding coefficient of 0.0016, the probability of inheriting two recessive disease genes from this founder is 0.000032. The incidence of autosomal dominant von Willebrand disease in Sottunga is greater than 10% while that of autosomal recessive tapetoretinal disease is 1.5%. We conclude, therefore, that the high frequencies of these diseases are not due to the disproportionate genetic contribution of one or a few particular founders. It is more likely that these disease genes occurred in high frequency in the initial population or were introduced repeatedly through time.

Finland↗
PubMed1988

Cesarean birth rate: small-geographic-area analysis.

Population-based analysis of cesarean section rates within 172 geographic areas in the Commonwealth of Massachusetts during fiscal year 1985 revealed a nearly normal distribution of observed-to-expected rates, implying that the forces that compel obstetricians to perform this surgical procedure are pervasive. However, a small number of areas were identified in which the number of procedures performed was significantly different from the state mean. During fiscal years 1982 to 1985, certain geographic subgroups consistently demonstrated incidence rates significantly greater than the state mean. Although variation (either overutilization or underutilization) from the state rate is not synonymous with inappropriate care, those physicians within the identified geographic areas must take responsibility for ascertaining the explanation for the variance.

Cesarean Section↗
PubMed1988

HLA sharing and fertility in Hutterite couples: evidence for prenatal selection against compatible fetuses.

Antigenic differences between mother and fetus (i.e., blood group incompatibilities) were traditionally considered deleterious for viviparous reproduction. Recently, evidence has accumulated suggesting that maternal response to paternally derived fetal antigens, paradoxically, may facilitate maintenance of pregnancy. Thus, fetuses whose paternally derived antigens do not differ from maternal antigens (i.e., histocompatible pregnancies) may be at a selective disadvantage during pregnancy. Parents sharing histocompatibility antigens (i.e., HLA) may produce compatible fetuses and show overall reduced fertility. Indeed, increased HLA sharing has been reported in some couples experiencing repetitive spontaneous abortion. However, the effects of HLA sharing in couples not selected because of previous pregnancy losses have not been assessed. To elucidate the reproductive effects of maternal-fetal histocompatibility, we initiated prospective population-based studies of parental HLA sharing and reproductive outcome in the Hutterites, a population isolate that lives communally and proscribes contraception. The relationship between HLA-A, -B, and -DR sharing and reproductive outcome was examined in 111 Hutterite couples. Intervals from marriage to each birth were no longer among couples sharing antigens; differences were significant at the second birth and remained significant through the sixth birth (P less than .05). When the effects of sharing at individual loci were examined, HLA-DR was the only individual locus that was a significant predictor of birth interval length (P = .025). Completed family sizes were 6.5 and 9.0 among couples sharing and not sharing HLA-DR, respectively (P = .082, 2-tailed). However, recognized fetal loss rates did not differ among couples sharing and not sharing antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Habitual↗
PubMed1987

Localization of neuropeptide Y mRNA in neurons of human cerebral cortex by means of in situ hybridization with a complementary RNA probe.

The distribution of mRNA encoding neuropeptide Y (NPY) in neurons of the normal human cerebral cortex in surgical biopsy specimens and postmortem brain was studied by in situ hybridization techniques. A 32P-labeled complementary RNA (cRNA) probe was used on cryostat sections of 13 formaldehyde-fixed cortical biopsy specimens. Hybridization to NPY mRNA was found in all samples: after autoradiography, discrete deposits of silver granules were observed on neuronal cell bodies abundantly distributed in the deep layers of the cortex, particularly laminae IV and VI, and on smaller cell bodies in the white matter. The localization of the neurons hybridized for NPY mRNA was comparable to that of NPY-immunoreactive cells as shown in sections from the same tissue blocks immunostained by using NPY antibodies. The specificity of the in situ hybridization technique was confirmed by blot hybridization analysis of electrophoretically fractionated RNA. This study clearly demonstrated the consistent localization of NPY gene transcription and expression in normal mature human cortical neurons.

Antibodies↗
PubMed1986

Mitotic inhibitors arrest the growth of Plasmodium falciparum.

We report that the mitotic inhibitor, vinblastine (VLB), is highly toxic to the malarial parasite, Plasmodium falciparum. In cultures in vitro growth is inhibited by 50% at a VLB level of about 28 nM, and totally abolished at a level of 100 nM. By tests on synchronized cultures we have found that the effect of VLB takes place at the trophozoite stage. Colcemid also inhibits schizogony with somewhat different kinetics. By mutagenesis with nitrosoguanidine followed by VLB selection we have isolated a VLB-resistant mutant which exhibits cross-resistance to vincristine. These data suggest a critical role of microtubules in the asexual schizogonic cycle of P. falciparum.

Animals↗
PubMed1986

The effect of age on blood pressure and heart rate variability in hypertension.

There is confusion in the literature as to the effect of ageing on blood pressure variability. The lack of consistency in reports probably reflects differences in blood pressure measurement techniques and in the choice of statistics used to describe variability. We studied 16 hypertensives (clinical blood pressure greater than 140/90 mmHg on 3 occasions) over 60 (67 +/- 5.5 years) and 16 under 60 years of age (44 +/- 8.9 years) using the Remler M 2000 ambulatory system to measure blood pressure and heart rate every 30 min during the awake hours of the day. Mean +/- s.e.m. blood pressure and heart rate for the elderly was 168 +/- 2.5/95 +/- 1.0 mmHg and 72 +/- 1.5 beats/min, corresponding values for the young being 162 +/- 5.3/103 +/- 2.1 and 78 +/- 2.5. Four statistics of variability were used: standard deviation, coefficient of variation, range and mean hourly change. Differences between old and young were found only for the range of systolic and diastolic blood pressure which was lower in the elderly (52 +/- 3.9/32 +/- 2.4 versus 67 +/- 5.2/46 +/- 4.8 mmHg, both P less than 0.05) and mean hourly change of heart rate (P less than 0.05). The standard deviation of heart rate was negatively correlated with age (r = -0.37; P less than 0.05). Only the systolic and diastolic blood pressure ranges were found to differ with age; the more rigorous tests of variability, standard deviation and coefficient of variation, were not changed. These data show that in hypertensives of different age but with roughly comparable blood pressure levels, variability of blood pressure is not consistently related to age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Report on variation in rates of utilization of surgical services in the Commonwealth of Massachusetts.

This article presents an analysis of over 140,000 selected surgical procedures performed in Massachusetts in 1980, giving the per capita rates of 14 common procedures and of four less frequently performed procedures. The analysis defines 172 geographic areas for the commonly performed procedures and 45 for the less frequently performed procedures. Per capita surgical rates among the defined areas are significantly different from both a statistical and a clinical point of view. Twofold and threefold variations occur frequently across geographic areas. In certain areas, some surgical services appear to be provided at rates substantially different from the statewide rate. We discuss the importance of these data for physicians as well as the implications for the distribution and quality of clinical care and for containment of medical care costs.

Costs and Cost Analysis↗
PubMed1985

Accuracy and reliability of the Del Mar Avionics pressurometer III.

We assessed the accuracy and reliability of the Avionics pressurometer, a fully automated ambulatory blood pressure recorder. Accuracy was assessed in 96 patients against the Hawksley random-zero sphygmomanometer. Two recordings were made with each device in a random sequence. No mean difference was found between methods. However, there was a marked variation in the difference between Avionics and Hawksley recordings. This was not due to variability in blood pressure alone since the agreement between Avionics and pressurometer systolic recordings (r = 0.88) was less than the agreement between sequential systolic blood pressure measurements with the Hawksley (r = 0.976, P < 0.001). In addition, a small degree of inter-device variability was demonstrated between three Avionics recorders, one device giving higher readings. Reliability was assessed in 30 patients during normal daily activities and compared with the Remler M2000. The rate of markedly artefactual recordings was higher with the Avionics. Thus, variability in Avionics recordings makes this device unreliable.

Blood Pressure Monitors↗
PubMed1985

Adverse effects of human leukocyte antigen-DR sharing on fertility: a cohort study in a human isolate.

To elucidate further the reproductive effects of human leukocyte antigen (HLA) sharing among spouses, we have been investigating prospectively the relationship between HLA-A, -B, and -DR sharing and reproductive outcome in the Hutterites, a religious isolate that proscribes contraception. For the first time the reproductive effects of HLA-DR sharing in a fertile population is reported in this article. Median intervals from marriage to first through fifth births were longer among couples who shared more than one HLA-A, -B, or -DR antigen. Longer intervals were associated with increased spontaneous abortion rates among couples who shared HLA-DR antigens (27%), compared with couples who shared only HLA-A or -B antigens (9%) and couples who shared no antigens (12%). Median completed family sizes were 5.0, 8.5, and 8.0 among the groups, respectively. However, some couples who shared HLA-DR antigens experienced no spontaneous abortions, despite ten or more pregnancies. Therefore, although HLA-DR compatibility, per se, is not deleterious, our data suggest a potentially important role for undefined HLA-linked genes in normal pregnancy.

Abortion, Spontaneous↗