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Biomedical subjects

P A Boyd

Publications and source records attributed to P A Boyd.

At least 19 recordsLinked to original sources
PubMed1996

Hydrogen peroxide and sequence-specific DNA damage in human cells.

Exposure of HeLa cells in monolayer culture to increasing concentrations of exogenously added H2O2 causes damage to cellular DNA. When the DNA is subsequently isolated from the non-apoptotic cells remaining in such cultures, evidence was obtained to suggest that the DNA damage elicited in intact cells was non-random and that certain nucleotide sequences associated with, or related to, the genes for heat shock protein 60 and catalase were more susceptible to damage than others. In contrast, these particular sequences were not specifically susceptible to damage when naked human DNA was exposed directly to H2O2 in vitro. On an overall comparative basis, sequences in the genes encoding catalase, alpha-1 antitrypsin and beta-actin appear more vulnerable to H2O2 in vivo, than sequences in H-ras and the P53 gene which seem surprisingly resistant.

Actins↗
PubMed1996

Genetic testing for cancer in children. Short-term psychological effect.

OBJECTIVE: To study the psychological effect of genetic testing in children. DESIGN: We evaluated the psychological effect of predictive genetic testing through surveys of children at risk for familial adenomatous polyposis. Their psychological state was assessed before testing and 3 months later. SETTING: A research clinic. PARTICIPANTS: A volunteer sample of 41 children, aged 6 to 16 years, and their parents. MAIN OUTCOME MEASURES: Self-report inventories of depression, anxiety, behavior problems, and competence. RESULTS: Nineteen children were found to have a gene mutation (mutation-positive) and 22 did not (mutation-negative). Their depression, anxiety, and behavior problem and competence scores remained in the normal range after testing. Also, parents' depression scores remained within normal limits at follow-up. There were subclinical changes, however. Mutation-positive children with affected mothers had significantly higher depression scores at follow-up. Also, regardless of test results, children with affected mothers had significantly increased anxiety scores after testing. In families with mutation-positive and mutation-negative children, familial adenomatous polyposis-unaffected parents experienced significantly increased depressive symptoms at follow-up. CONCLUSIONS: Predictive testing of children at risk for familial adenomatous polyposis did not lead to clinically significant psychological symptoms in tested children or their parents. However, it is premature to conclude that long-term follow-up will be equally favorable. Additional study will be needed to determine the families' understanding of the genetic information and the effect of the information on familial relationships.

Adenomatous Polyposis Coli↗
PubMed1996

Human heat shock protein gene polymorphisms and sudden infant death syndrome.

Comparison of the frequency of occurrence of restriction fragment length polymorphisms in control human DNAs and DNAs from infants dying from sudden infant death syndrome has indicated no significant difference in the case of restriction fragment length polymorphisms associated with the heat shock protein genes hsp70 and hsp90. A highly significant difference was detected, however, in the case of the specific restriction fragment length polymorphisms detected by an hsp60 gene probe in MspI digests.

Chaperonin 60↗
PubMed1996

Antenatal diagnosis of cystic hygroma or nuchal pad--report of 92 cases with follow up of survivors.

Information on the outcome of pregnancy was collected on 92 fetuses with cystic hygroma or nuchal pad, identified prenatally. Forty three (47% of the total) were associated with abnormal karyotype. Twenty five (27%) had normal karyotype but an additional abnormality was identified on ultrasound scan. There were 10 liveborn babies in this group of whom seven had significant problems postnatally. In twenty four (26%) cases the cystic hygroma or nuchal pad was an isolated finding. Seventeen (89% of those in which the pregnancy was electively continued) were liveborn and reported to be normal. Those with a normal karyotype, no other anomaly identified on antenatal scan, and smaller non-septate lesions have a good prognosis.

Adult↗
PubMed1996

Omphalocele and pericardial effusion: possible sonographic markers for the pentalogy of Cantrell or its variants.

BACKGROUND: The pentalogy of Cantrell consists of defects involving the diaphragm, abdominal wall, pericardium heart, and lower sternum. CASES: We report three cases of the pentalogy of Cantrell (variant form), involving an omphalocele complicated by an anterior diaphragmatic hernia. In two cases, a pericardial effusion was noted at antenatal scanning; the case without a pericardial effusion had an intact diaphragmatic pericardium at surgical repair. CONCLUSION: The presence of a pericardial effusion in association with an omphalocele should prompt a detailed search for other features of the pentalogy of Cantrell or its variants.

Abdominal Muscles↗
PubMed1995

Using decision analysis to compare policies for antenatal screening for Down's syndrome.

OBJECTIVE: To compare different screening policies for Down's syndrome across a broad range of outcomes, using decision analysis, with particular reference to the role of maternal serum testing. DESIGN: A decision tree was used to combine data from local sources and the medical literature to predict the likely frequency of several outcomes. Sensitivity analyses were used to test the robustness of the conclusions drawn. SETTING: Oxfordshire Health Authority. MAIN OUTCOME MEASURES: Live births with and without Down's syndrome; miscarriages with Down's syndrome; cases of Down's syndrome detected antenatally; amniocenteses performed (and associated miscarriages); direct NHS screening costs; number of women offered screening. RESULTS: Screening policies for Down's syndrome that include serum testing can produce better population outcomes than programmes that do not. Each option for screening for Down's syndrome that we considered had significant drawbacks. In Oxfordshire, offering serum testing to women of all ages would prevent the birth of approximately one more baby with Down's syndrome per year than would a policy of screening for women aged 30 years or more. The cost of preventing this one extra Down's birth would be one or two normal babies lost after amniocentesis, 4500 blood tests for young women (with the associated anxiety and counselling), approximately 200 false positive serum test results and amniocenteses (with the associated anxiety and distress), and 90,000 pounds for the extra tests, counselling, and amniocenteses. Opinions are divided as to which policy is the better option for the population. CONCLUSIONS: Decision analysis is a useful tool for determining the likely consequences of different policy options across a broad range of outcomes. This focuses debate and decision making on outcomes of care, which in turn makes it clear that the choice of screening programme for Down's syndrome depends on the relative importance ascribed to the different outcomes. If individuals' values vary widely it may be impossible to find one screening policy that meets the needs of all pregnant women.

Adult↗
PubMed1995

Unilateral injury of posterior parietal cortex and spatial learning in hooded rats.

The influences of bilateral or unilateral injuries within the posterior parietal cortex (PPC) upon spatial learning in a water maze were examined in three experiments. Place-learning and response-learning were investigated in a four-alley 'Greek-cross' shaped water maze with extra-maze visual cues available. No differences were detected on any of several measures sensitive to learning between the lesion groups on the place-learning task. Microanalysis of behavior within trials revealed that animals with either bilateral or right unilateral PPC injuries committed significantly more total errors, initial alley entrance ('reference memory') errors, and re-entry ('working memory') errors in the response-learning paradigm than did either the control or left PPC-injured rats. No differences were detected between the latter two groups on these measures. Unilateral lesions resulted in asymmetrical placing responses ipsilateral to the injury 10 days after surgery whereas bilateral injuries resulted in asymmetrical placing with mixed directionality. The acquisition of the response-learning problem in the absence of visual cues was studied on animals prepared with unilateral lesions and housed post-operatively either in isolation or in a 'complex environment.' In the absence of visual cues both right and left PPC-injured rats committed more errors than sham controls, and differential post-surgical housing did not attenuate these impairments. These same animals were trained on the landmark navigation task. Although no differences appeared between the lesion groups, a generalized but transient facilitation of learning was observed in animals housed in the 'complex' environment. Unilateral injuries placed in sham controls failed to disturb retention of the landmark navigation strategy. Because none of the PPC-injured animals were deficient in the landmark task, a result which is contrary to observations in other laboratories, the influence of post-surgical recovery interval upon acquisition of the landmark navigation strategy was explored. Animals were prepared with right PPC injuries and trained following either a 5 or 35 day recovery interval. Only those animals limited to the short recovery interval proved to have a spatial deficit in the landmark task. It is concluded that injuries in the PPC of either hemisphere disturb egocentric spatial functions. However, animals with left PPC injuries are able to compensate by using allocentric visual cues if they are available. It is due to the special role played by the right PPC in complex visuospatial functions that animals with this injury are unable to compensate.

Animals↗
PubMed1995

Maternal 3;13 chromosome insertion, with severe pre-eclampsia.

A previously healthy young primigravida suffered very severe pre-eclampsia and was delivered at 32 weeks gestation. The baby was growth retarded with dysmorphic features, and died aged 4 days. Chromosome analysis of the baby revealed partial trisomy 13 resulting from recombination within a maternal insertion of part of 13q into 3p. To date, the maternal insertion has been identified in a further three members of the family and may have contributed to a number of spontaneous abortions, stillbirths and neonatal deaths in other family members. The various possibilities for recombination and malsegregation are discussed. An association between pre-eclampsia and trisomy 13 has been reported previously. To our knowledge this present paper constitutes the first report of partial trisomy for 13q occurring with pre-eclampsia.

Adult↗
PubMed1995

Gene tests and counseling for colorectal cancer risk: lessons from familial polyposis.

Familial adenomatous polyposis (FAP) is a well-defined, inherited colorectal cancer syndrome due to mutations in the APC gene. Genetic counseling and predictive gene tests for FAP will likely be incorporated as a first step in risk assessment for this condition. Our experience with predictive gene testing for FAP sheds important light on the impact of such tests for families at risk for FAP or colorectal cancer. We counseled and tested 47 adults and 36 minors at risk for FAP. Gene test results changed the risk of FAP for a given individual from a priori 50% to essentially zero or 100%. These individuals and their family members were interviewed before and after disclosures of APC gene test results to examine issues related to patients' knowledge about FAP, risk perception, reasons for seeking gene testing, and anticipated meaning of the results. We found that the gene test is imbued with meaning beyond determination of gene status in families who choose gene testing. The at-risk patient has preformed, well-entrenched conceptions of what having FAP or colorectal cancer entails, and family relationships and identity may be strongly linked with disease or gene status. We have found that genetic testing of minors requires additional counseling considerations and effort to ensure their understanding of FAP and the gene test. Importantly, their understanding of the clinical and social meaning of the gene test result must be elicited. For all patients, the value of counseling includes reduction of uncertainty and adjustment of misperceptions. Genetic counseling guidelines for this emerging clinical service are presented.

Adenomatous Polyposis Coli↗
PubMed1994

Analysis of limb reduction defects in babies exposed to chorionic villus sampling.

In 1991 we reported a cluster of babies with limb abnormalities and suggested that chorionic villus sampling (CVS) was aetiologically associated with these defects. To address the issue more objectively, we have assessed reported limb reduction defects in 75 babies exposed to CVS in utero. 13 babies had an absent limb or a defect through the humerus or femur; 9 had defects through the radius or tibia; 22 defects of the carpus, tarsus, metacarpus, or metatarsus; 25 defects of the digits; and 6 defects of the terminal phalanx or nail only. There was a strong correlation between the severity of the defects and the duration of gestation when CVS was done. The median gestational age at CVS ranged from 56 (range 49-65) postmenstrual days for the most severe category to 72 (51-98) days for the least severe. The relation was seen for both isolated limb defects and for cases with oromandibular-limb hypogenesis syndromes. This relation is further evidence that CVS has an aetiological role in some limb reduction anomalies.

Abnormalities, Multiple↗
PubMed1994

Reducing the need for amniocentesis in women 35 years of age or older with serum markers for screening.

BACKGROUND: As maternal age advances, the risk of fetal Down's syndrome increases. Pregnant women 35 years of age or older are routinely offered amniocentesis because of this risk. Recently, maternal serum markers have been reported to be useful in screening for Down's syndrome, primarily in younger women. We therefore investigated whether offering amniocentesis only to selected women 35 years of age or older who were identified by screening measurements in serum might prove a useful alternative to the current practice. METHODS: We studied 5385 women with singleton pregnancies who were 35 years of age or older and were undergoing routine amniocentesis. Along with information about the pregnancy, we obtained a serum sample for measurement of alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin. Individual estimates of the risk of Down's syndrome in the fetus were calculated for each pregnancy before the karyotype was known. RESULTS: If amniocentesis had been reserved for the women calculated to have a risk greater than 1 in 200 of having a fetus with Down's syndrome, 48 of the 54 cases of Down's syndrome (89 percent) would have been identified, 25 percent of the unaffected pregnancies would also have been identified as being at high risk for Down's syndrome (false positives). Seven of 15 fetuses (47 percent) with other trisomies, 11 of 25 (44 percent) with sex aneuploidy, and 1 of 9 (11 percent) with miscellaneous chromosomal abnormalities would also have been detected. In practice, such screening would have made 75 percent of the amniocentesis unnecessary, along with a proportion of the amniocentesis-associated fetal losses. If the cutoff for the risk of Down's syndrome were set higher than 1 in 200, both the rate of detection and the false positive rate would be lower. Conversely, these rates would be higher if the cutoff were set lower. CONCLUSIONS: Prenatal screening of serum to generate individual estimates of the risk of Down's syndrome in the fetus can provide a basis for decision making in the cases of women 35 years of age or older, as it does in younger pregnant women, and is an alternative to current testing practices.

Adult↗
PubMed1994

Hereditary multiple intestinal atresia--ultrasound findings and outcome of pregnancy in an affected case.

A case of multiple intestinal atresia is described. Dilatation of the bowel was observed at 17 weeks' gestation during routine ultrasound scan of a healthy Caucasian primigravida from a non-consanguineous marriage. Amniocentesis was performed. The karyotype was normal male and cystic fibrosis screening was negative. Regular scans were performed throughout the pregnancy and a simple bowel obstruction was suspected. The baby was delivered at 37 weeks' gestation in good condition. Initial clinical examination was normal but abdominal distension developed during the first day. At laparotomy, prepyloric septal atresia, a distal duodenal membrane, and multiple intestinal atresia were found. The baby died aged 4 days. Post-mortem examination of the abdomen confirmed the absence of lumen from long segments of the small intestine together with areas of colonic atresia. Histology and distribution were consistent with those reported in familial multiple intestinal atresia. The pitfalls in the interpretation of prenatal ultrasound scans and the possibility of prenatal diagnosis in future pregnancies are discussed.

Fatal Outcome↗
PubMed1993

An economic appraisal of alternative pre-natal screening programmes for Down's syndrome.

The objective of this study was to evaluate economically a screening programme within the Oxford Regional Health Authority for Down's syndrome, based on maternal serum alpha fetoprotein, unconjugated oestriol and human chorionic gonadotrophin as well as maternal age (the triple test) against maternal age alone. The design of the study involved cost-effectiveness analysis of the triple test relative to the maternal age screening programme, and the main outcome measure was the cost per Down's birth avoided. It was found that the triple test is more cost-effective over a wide range of assumptions concerning detection rates and procedure costs. Indirect costs are important in considering the cost-effectiveness of the screening programmes. The most efficient detection rate is around 58 per cent for which the cost per Down's birth avoided is approximately 29,600 pounds if only direct costs are evaluated, 20,100 pounds if all NHS costs are considered and -49,800 pounds if all resource consequences are analysed. It may be concluded that screening for Down's syndrome using the triple test is cost-effective over a wide range of assumptions concerning detection rate and procedure costs. If all resource costs are considered, the programme is highly cost-effective in comparison with other health care interventions.

Abortion, Therapeutic↗
PubMed1993

Molecular studies of trisomy 18.

We have determined the parental origin of 50 cases of trisomy 18. In 48 cases the additional chromosome was maternal in origin, and in 2 cases it was paternal in origin. Seven cases, including both those with an additional paternal chromosome, appeared to be the result of postzygotic error. In contrast to the situation in nondisjunction involving chromosomes 21 and X, there was no evidence for nullochiasmate nondisjunction.

Adolescent↗