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Biomedical subjects

R A Doherty

Publications and source records attributed to R A Doherty.

At least 19 recordsLinked to original sources
PubMed1999

Issues in implementing prenatal screening for cystic fibrosis: results of a working conference.

OBJECTIVE: To summarise a conference convened to examine how cystic fibrosis screening might appropriately be introduced into routine prenatal practice. METHODS: Participants included experts from various relevant disciplines. Systematic reviews and data from individual trials were presented; issues were identified and discussed. RESULTS: Judged by published criteria, prenatal cystic fibrosis screening is suitable for introduction. Screening can be performed cost effectively by identifying racial/ethnic groups at sufficient risk and then using either of two models for delivering laboratory services. Validated educational materials exist. Ethical issues are not unique. CONCLUSIONS: Once adequate facilities for patient and provider education, testing, counselling, quality control, and monitoring are in place, individual programmes can begin prenatal screening for cystic fibrosis.

Clinical Trials as Topic↗
PubMed1997

Prenatal screening for cystic fibrosis: an updated perspective.

In U.S. white populations prenatal screening for cystic fibrosis can identify > or = 60% of pregnancies in which the risk for an affected fetus is high. Such pregnancies occur when both the mother and the father carry cystic fibrosis mutations; about one screened couple per 1000 falls into this category. The risk of the fetus being affected is 1 in 4. Prenatal screening for cystic fibrosis compares favorably with prenatal screening for spina bifida and Down syndrome, with a similar detection rate, a much lower false-positive rate, and greater odds of being affected, given a positive result. Intervention trials in Europe and the United States provide documentation of efficacy. Larger-scale trials should now be encouraged in the United States to gain further insight into program design and case management, as a way to determine the feasibility of cystic fibrosis screening as part of routine prenatal care.

Clinical Protocols↗
PubMed1996

Couple-based prenatal screening for cystic fibrosis in primary care settings.

This study examines a couple-based screening protocol for cystic fibrosis (CF) during pregnancy. The screening test is positive only when both partners carry an identifiable mutation. The risk for the fetus to be homozygous is 1 in 4, and definitive prenatal diagnostic testing can be offered. Between six and seven of every ten CF cases can be identified by testing for seven CF mutations. Couple screening for CF has not been evaluated in a decentralized health-care system. Office guides, informational materials, and consent forms were provided to 69 physicians in Maine. Women sent buccal samples to the study centre and brought sampling materials to their partners. Samples from both individuals were required. When a mutation was identified in the woman's sample, the partner's sample was tested. Screening results were reported to the physician. Standardized follow-up surveys were carried out in selected women, key office staff, and physicians. 1770 women and 1682 partners submitted samples. Testing was successfully completed for 1645 couples. Screening results were positive in one couple; the fetus was homozygous for CF. Physicians, office staff, and nearly all women were satisfied with the screening process. Couple screening for CF is feasible and acceptable in decentralized primary care settings.

Adult↗
PubMed1992

Estimation of the male and female mutation rates in Duchenne muscular dystrophy (DMD).

We present the results of an international collaborative study aimed at estimating the ratio of male to female mutation rates in Duchenne muscular dystrophy based on the method of C. Müller and T. Grimm. With a sample size of 295, this ratio is found to be very close to 1, thus giving evidence for equal mutation rates in males and females in Duchenne muscular dystrophy.

Blotting, Southern↗
PubMed1992

White blood cell immunization and anticardiolipin antibody levels in women with recurrent miscarriages.

To determine whether WBC immunization stimulates production of anticardiolipin antibodies, anticardiolipin antibodies were measured before and 6 weeks after WBC immunization. Twenty-four non-pregnant women, who had had recurrent miscarriages for which a definitive cause could not be determined, were immunized with their partner's WBC. No significant differences in levels of anticardiolipin antibodies were detected between paired samples of sera obtained before and 6 weeks after WBC immunization. White cell immunization in nonpregnant women did not stimulate production of anticardiolipin antibodies.

Abortion, Habitual↗
PubMed1989

Genealogical analysis of cystic fibrosis families and chromosome 7q RFLP haplotypes in the Hutterite Brethren.

In the 100-year period 1880-1980 the Hutterite population increased from about 442 to 23,000 individuals in North America. There are three endogamous subdivisions in this Caucasian genetic isolate. A total of 11 cystic fibrosis (CF) families from Canada and the United States were investigated, including at least two families from each of the three subdivisions, the Dariusleut, Lehrerleut, and Schmiedeleut. A study of RFLPs for the loci D7S8, D7S23, MET, and D7S18 (also called D7S16) in the region of the CF gene in 10 families shows considerable genetic variability. There were three different extended CF gene-region haplotypes on CF chromosomes (CF haplotypes), and there were 13 different extended CF gene-region haplotypes on normal chromosomes (normal haplotypes). The three CF haplotypes have different D7S23 and MET haplotypes. Parents who have the same CF haplotype are, on the average, more closely related than parents who have different haplotypes, but only within the same subdivision. A marriage node graph of 11 families illustrates the complexity of Hutterite genealogies. The frequency distribution of CF haplotypes in the Hutterite sample differs notably from those of larger agglomerates of family data from collaborative studies, with respect to D7S8, MET haplotypes, and D7S23 haplotypes. We propose that there were at least three CF carriers among the founders of the Hutterite population and that copies of a particular CF haplotype in current individuals are identical by descent. The alternative that one or more genetically distinguishable CF haplotypes resulted from recombination since the founding of the population is considered to be less likely.

Canada↗
PubMed1987

Genetic heterogeneity in Duchenne dystrophy.

We evaluated 173 patients in the Clinical Investigation of Duchenne Dystrophy study to determine if patients from the same kindred were more alike clinically than patients within the study population as a whole. A high intrafamilial correlation was noted for age-adjusted muscle strength scores. While noninherited factors could, in part, explain the results, it seems likely that genetic heterogeneity may contribute to the observed similarity within Duchenne dystrophy kindreds.

Adolescent↗
PubMed1987

Use of serum creatine kinase, pyruvate kinase, and genetic linkage for carrier detection in Duchenne and Becker dystrophy.

Carrier detection in Duchenne dystrophy (DD) and Becker dystrophy (BD) can be achieved with DNA probes that recognize restriction fragment length polymorphisms (RFLPs). In 22 families, we found that 16 of 23 females at risk for being DD or BD carriers could be provided with more definitive indications of carrier status beyond the use of creatine kinase/pyruvate kinase and pedigree analysis. RFLP analysis was not possible for six individuals despite potentially informative probes, because family members critical to the analysis were unavailable. In only one instance were all eight probes uninformative.

Creatine Kinase↗
PubMed1987

Carrier assessment for mothers and sisters of isolated Duchenne dystrophy cases: the importance of serum enzyme determinations.

DNA studies (restriction fragment length polymorphism linkage analysis and deletion analysis with pERT87) and serum creatine kinase/pyruvate kinase (CK/PK) measurements were done to determine the carrier status of 59 mothers and sisters of isolated Duchenne dystrophy (DD) cases. The results of DNA studies modified the carrier risks for 34 of the 59 (58%), but the derived risks often did not differ importantly from risks calculated by conventional methods. Elevated CK/PK provided strong evidence of the carrier state for 24 of the 59 (41%), and CK/PK frequently provided data unavailable through DNA studies. Serum enzyme determinations remain an important means of evaluating DD carrier suspects and are especially valuable in isolated-case families. Enzyme testing should be combined with DNA studies to achieve the best estimate of carrier risk.

Creatine Kinase↗
PubMed1986

Reproduction and growth following prenatal methylmercuric chloride exposure in mice.

Reproductive effects of the environmental pollutant methylmercuric chloride administered as a single dose per os during pregnancy were studied both in treated mice (G0 generation) and in their prenatally exposed offspring (G1). Treatment at 9.5 days postfertilization caused no observed effects at doses as high as 12-18 mg Hg+/kg. In contrast, treatment at 12.5 and 15.5 days produced toxicity; results were similar and were combined for analysis. Among G0 mice, the percentage capable of delivering one or more viable pups showed an estimated threshold level response at 8.0 mg/kg. The percentage of G1 pups that were viable at 1 day post partum was significantly dose-related, with an approximate threshold exposure level of 4.3 mg/kg. Among the surviving G1 offspring, body weight in adulthood (8 months) showed a statistically significant reduction that was also dose-related. Fertility testing of G1 offspring revealed no treatment effects on mating behavior judged by time interval between pairing and parturition. However, there was a trend (statistically nonsignificant) toward a dose effect on sizes of females' litters. Sterility (inability to produce offspring) did not occur either among G1 males at 4 months of age (N = 30; dose 8-12 mg/kg) or among females up to the advanced reproductive age of 14 months (N = 29; dose 5.3-12 mg/kg). We conclude that mice exposed prenatally to methylmercuric chloride revealed no greater susceptibility to sterility than to perinatal mortality.

Animals↗
PubMed1985

Flow cytometric detection of lymphocyte alterations in Huntington's disease.

Several recent reports indicate that patients with Huntington's Disease (HD) may manifest membrane abnormalities in a wide variety of cells including peripheral blood lymphocytes. In this study, flow cytometry is used in conjunction with the fluorescent membrane probe, 8-anilino-1-naphthalene sulfonate (ANS), to examine peripheral blood lymphocytes from 16 HD patients and 14 age- and diet-matched control subjects. Increased ANS fluorescence intensity of lymphocytes (p less than 0.02) was found in HD patients as compared to control subjects. These differences are masked when the mean fluorescence of the total leukocyte population is measured, possibly explaining conflicting data of other investigators. These observed differences in ANS fluorescence intensity between HD patients and control subjects support the concept of a gene defect which may be expressed as membrane alterations in non-neural as well as neural cells. The selective alterations of lymphocytes may also reflect altered immunological activity reported in HD.

Adult↗
PubMed1985

Supernumerary microchromosomes identified as inverted duplications of chromosome 15: a report of three cases.

Supernumerary bisatellited microchromosomes detected in three unrelated patients were identified as inverted duplications of chromosome 15. Each of these chromosomes contained a small euchromatic interstitial band presumably derived from the proximal portion of region 15q1. The clinical significance of this material was difficult to assess. Two of our cases were ascertained as the result of routine amniotic fluid studies. One of the affected fetuses had an unusual form of mosaicism 46,XY/48,XY, + inv dup(15), + inv dup(15), but no apparent developmental abnormalities. The inv dup (15) of the second fetus was familial in origin; no phenotypic abnormalities or evidence of mosaicism were detected in the carrier parent. The third inv dup(15) was found in a 20.5-month-old boy referred for developmental retardation. The clinical findings in this case were similar to those seen in patients with large inv dup(15)'s and did not suggest Prader-Willi syndrome.

Abnormalities, Multiple↗
PubMed1985

More precise localization of the human factor IX gene by in situ hybridization.

The location of the human antihemophilic Factor IX has been more specifically assigned from the region Xq27----qter to Xq26----q27 by quantitative in situ hybridization. The present study utilized a complex hybridization probe and prephotographed G-banded human chromosomes to improve analytical sensitivity and accuracy.

Chromosome Banding↗