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Biomedical subjects

A J Dawson

Publications and source records attributed to A J Dawson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Functional mosaic trisomy of 1q12-->1q21 resulting from X-autosome insertion translocation with random inactivation.

Cytogenetic studies of a 16-year-old female with behaviour and learning problems revealed that one X chromosome had additional material inserted at Xq21. Fluorescence in situ hybridization (FISH) analysis showed that the inserted segment contained heterochromatin and adjacent euchromatin of chromosome 1 origin. The karyotype of this patient was established as: 46,X,der(X)ins(X;?)(q21;?).ish der(X) ins(X;1)(q21;q12q21)(wcp1+). Chromosome replication studies demonstrated a random pattern of X inactivation, suggesting that the inserted material may be too 'small' to skew lyonization. The consequences of this abnormal X chromosome in relation to the clinical phenotype are discussed.

Adolescent↗
PubMed1998

The evaluation of 15q proximal duplications by FISH.

Six patients from the clinical cytogenetics laboratory identified as having the normal variant dup(15)(q12) were further evaluated using fluorescence in situ hybridization (FISH). The purpose of this study was to ascertain whether any of the Prader Willi Angelman Chromosome Region (PWCR and ANCR, respectively) loci were duplicated in these patients. The results indicated that the patients could be categorized into two groups. The first group showed no duplication of the PWCR ANCR loci and appeared to belong to the dup(15)(q12) class which is phenotypically silent and is therefore called the normal variant. The second group also showed no duplication of the PWCR/ANCR loci. but had a large alpha satellite variant with D15Z. It is hypothesized that these patients do not have a duplication of 15q12 but rather a centromeric variant which mimics the dup(15)(q12). This study confirms the importance of evaluating apparent variations in the proximal region of chromosome 15 with FISH.

Angelman Syndrome↗
PubMed1997

Low MSAFP levels and Williams syndrome.

Williams syndrome (WS) is associated with a deletion of the elastin gene in over 90% of cases. We report maternal serum alpha feto-protein (MSAFP) levels in 5 women whose fetuses were later diagnosed as having WS. MSAFP levels ranged from 0.5-0.8 multiples of the median (MOM). Although further confirmation is necessary, it appears that MSAFP levels are lower than the median in WS. This apparent association has implications for counselling women following maternal serum screening.

Female↗
PubMed1997

Familial transmission of a small supernumerary marker chromosome 8 identified by FISH: an update.

A father and his 2 daughters were previously determined to carry a small, supernumerary marker chromosome [Chudley et al., 1983]. The origin of this marker could not be determined by standard cytogenetic techniques. In this study, fluorescence in situ hybridization (FISH) studies identified the marker chromosome as a pericentric derivative of chromosome 8. The father has low grade mosaicism for this marker and is phenotypically normal. Both daughters are non-mosaic and show developmental delays and somewhat differing clinical findings. The phenotypes of the 2 sisters are compared with those previously reported for supernumerary der(8) patients. This is the first report of familial transmission of a supernumerary der(8) marker chromosome.

Adolescent↗
PubMed1997

Proximal interstitial 6q deletion: a recognizable syndrome.

We report on an 8-year-old boy with a proximal interstitial deletion of the long arm of chromosome 6 with breakpoints q13 to q14.2. He has a characteristic facial appearance that is seen in several of the previously described cases. Details of his clinical course are reviewed and compared with the nine previous reported cases of the proximal deletion 6q syndrome.

Abnormalities, Multiple↗
PubMed1996

Characteristics of nerve growth factor induced hyperalgesia in adult rats: dependence on enhanced bradykinin-1 receptor activity but not neurokinin-1 receptor activation.

Treatment of adult rats with a single dose of nerve growth factor (NGF, 1 mg/kg, i.p.) results in a prolonged hypersensitivity to noxious thermal stimulation which becomes noticeable within 30 min of administration and lasts for several days. A significant mechanical hyperalgesia develops within 7 h following injection of NGF and persists for up to 7 days. In the present set of experiments we describe certain quantitative features of this hyperalgesia. The initial thermal hyperalgesia can be highly variable and is associated to some degree with the presence of an overt immunologic reaction. The mechanical hyperalgesia is reproducible enough to reveal a clear dependency on the dose of NGF. We also examined the pharmacological properties of the NGF-induced hyperalgesia. The bradykinin BK1 receptor antagonist des-Arg9[Leu8]BK transiently blocked the thermal hyperalgesia when injected 1 day after NGF administration whereas mechanical thresholds were further reduced under this protocol. The BK2 antagonist HOE 140 had no effect on this late NGF-induced hyperalgesia. Injection of the neurokinin NK1 receptor antagonist CP-96345 or its inactive enantiomer CP-96344 one day after NGF both induced a transient block of NGF-induced thermal hyperalgesia indicating a non-specific effect rather than an action at NK1 receptors. This was confirmed by finding no reversal of NGF-induced hyperalgesia by RP67580, another NK1 receptor blocker. These results suggest upregulation and activation of BK1 but not NK1 receptors as an additional, probably peripheral, mechanism for the late phase of NGF-induced thermal hyperalgesia.

Adrenergic beta-Antagonists↗
PubMed1996

Der(22)t(11;22) resulting from a paternal de novo translocation, adjacent 1 segregation, and maternal heterodisomy of chromosome 22.

The t(11;22) (q23;q11) translocation is the most frequently identified familial reciprocal translocation in humans. In translocation carriers, 3:1 meiotic segregation with tertiary trisomy can occur resulting in abnormal progeny with the der(22) as the supernumary chromosome. Affected children have a distinct phenotype with multiple anomalies and severe mental retardation. We have identified a child with developmental delay and multiple anomalies consistent with the der(22) phenotype. Cytogenetic analysis showed an abnormal chromosome complement of 47,XX,+der(22)t(11;22)(q23; q11) in all 50 cells analysed. FISH analysis using chromosome 11 and 22 painting probes showed a pattern consistent with a reciprocal translocation of the distal bands 11q23 and 22q11 respectively. Parental karyotypes were normal. RFLP analysis of locus D22S43, which maps above the t(11;22) breakpoint, showed that the der(22) was paternal in origin and indicated that the normal chromosomes 22 were the probable result of maternal heterodisomy. RFLP analysis of locus D22S94, which maps below the t(11;22) breakpoint, also suggested that both normal chromosomes 22 of the child represented the two maternal homologues. Non-paternity was excluded through the analysis of 10 microsatellite markers distributed on 10 different chromosomes and three VNTRs on three different chromosomes. To the best of our knowledge, this is the first reported case of a patient with an abnormal karyotype resulting from a de novo translocation in the paternal germline with probable unbalanced adjacent 1 segregation and maternal non-disjunction of chromosome 22 in meiosis I.

Abnormalities, Multiple↗
PubMed1996

The regionalization of perinatal care in Wales and Washington State.

OBJECTIVES: The purpose of this study was to compare perinatal regionalization and neonatal mortality in Wales and Washington State. METHODS: The 28 hospitals in Wales and the 80 hospitals in Washington State that offered maternity services and the 218,326 births that occurred in these hospitals in 1989 and 1990 were studied. Surveys were used to identify the neonatal technology and the referral policies of each hospital, and linked data from birth and death certificates were used to examine birthweight-specific neonatal mortality rates for all babies born in these hospitals. RESULTS: Welsh district general hospitals (broadly equivalent to Level II perinatal centers in the United States) have more sophisticated neonatal technology than their Washington State counterparts and appear less likely to refer small or preterm babies to regional or subregional centers. Neonatal mortality rates were quite similar in the two settings. CONCLUSIONS: Perinatal care in Wales appears to be less regionalized than in a similar region in the United States. The relative lack of perinatal regionalization in Wales may contribute to duplication and underutilization of expensive neonatal technologies. National health care systems do not, in and of themselves, lead to optimal regionalization of services.

Birth Certificates↗
PubMed1995

Prenatal diagnosis of ring chromosome 6.

An amniocentesis was performed on a gravida 1, para 0 23-year-old female because of high maternal serum alpha-fetoprotein and nuchal thickening/cystic mass apparent on the fetal ultrasound. Detailed ultrasound examination revealed multiple anomalies including brain abnormalities. The fetus was found to have a mosaic female karyotype: 45,XX, - 6/46,XX,r(6) (p25q27) (62 per cent:38 per cent). This is the first report of a prenatally diagnosed case of ring chromosome 6.

Adult↗
PubMed1995

Frequency of FMR1 premutations in a consecutive newborn population by PCR screening of Guthrie blood spots.

The fragile X(A) or FRAXA syndrome is the most common form of familial mental retardation and is associated with a fragile site at Xq27.3. The gene responsible for the FRAXA syndrome, the FMR1 gene, has been cloned. inactivation of the FMR1 gene is associated with amplification of a trinucle-otide CGG repeat sequence and methylation of an adjacent CpG island. Previous estimates for the prevalence of the FRAXA syndrome have been based on indirect methods of chromosome analysis in institutions and community workshops for the mentally handicapped. We have analyzed the frequency of premutations of the FMR1 gene in 3002 X chromosomes of 1000 male and 1000 female consecutive newborn nonautoclaved blood spots in an anonymous, unlinked survey. The CGG repeat sizes were calculated by measuring the length of products of the PCR reaction based on the molecular size of labeled markers in a denaturing sequencing gel assay. For consistent PCR amplification a DNA microextraction was necessary, including a phenol/chloroform series. In our population, the CGG allele ranged from 9 to 106 repeats: 97% of alleles had fewer than 40 repeats. The most frequent allele was a repeat of 28. Approximately 2.3% of alleles had CGG repeats ranging from 4 to 49 and 0.37% of alleles had repeats ranging from 50 to 59. The frequency of alleles > 60 repeats in the Manitoba male population is approximately 0.13%. The use of nonautoclaved Guthrie blood spots for population screening of FRAXA premutations is not recommended. The necessity of a phenol/chloroform DNA microextraction is tedious and time consuming. The low yield of DNA (250 ng) does not allow for reanalysis by Southern of apparently homozygous females with potentially unstable CGG alleles in the 40-60 repeat range and likely underestimates premutation carrier status.

Alleles↗
PubMed1995

A comparison of the investment in hospital-based obstetrical ultrasound in Wales and Washington state.

The purpose of this study was to examine differences in the way Britain and the United States invest in and deploy a new medical technology. We used structured interviews to obtain information on the technical sophistication and approximate replacement value of all hospital-based obstetrical ultrasound machines in every maternity hospital in Washington state and Wales. The supply of hospital-based ultrasound machines--approximately two machines per 1,000 births--was similar in both countries. Wales had fewer advanced ultrasound machines than Washington state, and they were based exclusively in high-volume district general hospitals; there were no obstetric ultrasound machines in the private sector. In Washington state, the majority of advanced machines were in small and medium-sized hospitals, and many private offices had ultrasound machines. The approximate replacement value of hospital-based machines was three times as high per birth in Washington state as in Wales. In the case of obstetrical ultrasound, centralization of facilities, a relatively small private sector, and global budgeting lead to lower expenditures per patient within the National Health Service without compromising access to care.

Birth Rate↗
PubMed1995

Perinatal and infant postmortem examinations: how well are we doing?

AIM: To investigate the quality of perinatal and infant necropsies and assess the relation between the quality and value of this investigation in different outcome groups. METHODS: Cohort analysis of 540 deaths during 1993 of babies between 20 weeks' gestation and one year of age born to women usually resident in Wales. Cases were identified from the All Wales Perinatal Survey. Each case was assessed to establish whether the necropsy yielded clinically relevant information. The quality of necropsy was assessed by scoring aspects identified as being part of the necropsy. RESULTS: Necropsy was performed in 335 (62%) cases, and the report was available for assessment in 314 cases. The quality of necropsy was below the minimum standard in 46% (143/314) of cases. The highest quality necropsies were carried out on fetal deaths at 20 to 23 weeks' gestation (12% (10/85) below standard), compared with 65% (87/133) below standard on stillbirths and 68% (21/31) on sudden unexpected infant death. Overall, 42% (131/314) of necropsies were performed in a regional paediatric pathology centre including 88% (76/88) of fetal deaths, 23% (31/133) of stillbirths and 30% (29/96) of infant deaths. The quality score for the necropsy performed in a regional centre failed to achieve the minimum acceptable score in 8% (11/131) of cases compared with 72% (132/182) for those done elsewhere. The cause of death was detected by necropsy in 17% (52/314) of cases. The quality of necropsy was significantly higher when the cause of death was revealed than when nothing new was found. CONCLUSIONS: The overall quality of the perinatal and infant necropsy is poor. This is regrettable as valuable information can be revealed frequently by a good quality necropsy. Adherence to Guidelines for Postmortem Reports recently published by the Royal College of Pathologists should improve the situation.

Abortion, Spontaneous↗
PubMed1993

Rapid prenatal diagnosis of Patau's syndrome in a fetus with an abdominal wall defect by 72 hour culture of cells from amniotic fluid.

A woman in the 32nd week of pregnancy was referred for investigation because of fetal abnormalities, including an abdominal wall defect, detected by ultrasonography. In view of the increased risk of chromosome abnormality, amniocentesis was performed to enable informed decisions about the management of the pregnancy and delivery to be taken. Cells from the liquor were inoculated into standard lymphocyte culture medium and incubated for 72 h. Slides with a high mitotic index and good quality metaphases, comparable to those from a blood culture, were obtained after harvesting. Cytogenetic analysis showed the karyotype to be 46,XY, - 14,+t(13q14q), which is consistent with Patau's syndrome. This technique appears to be an option for rapid karyotyping in cases of abdominal wall defect, where a chromosomal abnormality is suspected.

Abdominal Muscles↗
PubMed1993

Age-specific detection and false-positive rates: an aid to counseling in Down syndrome risk screening.

OBJECTIVE: To determine whether the serum screening test for Down syndrome provides equal detection efficacy for women of all ages, to improve the data available for patient counseling both before testing and afterward in the event of a positive result. METHODS: We examined the effect of age on Down screening by generating a set of "normal" and "Down syndrome" likelihood ratios by computer simulation. The expected false-positive and detection rates were derived for different age groups by counting the proportion of cases in which the likelihood ratio could modify the age-specific risk to be greater than the cutoff risk of one in 300 (equivalent to an incidence of 3.33 per 1000). The predictive value of a positive result was calculated using Baye's theorem. RESULTS: Detection rates, false-positive rates, and predictive values were shown to be age-dependent. CONCLUSIONS: Knowledge of the age dependency of Down syndrome screening results may be useful in explaining to patients that the Down screen can only detect a proportion of cases and that a negative result does not guarantee normality. This knowledge may also be helpful in minimizing psychological stress, as a positive result indicates only a small chance that the fetus will have Down syndrome.

Adolescent↗
PubMed1992

External ocular trauma in instrumental and normal deliveries.

OBJECTIVE: To compare the occurrence of external ocular trauma in instrumental and normal deliveries. DESIGN: Prospective controlled study. SETTING: University Hospital of Wales, Cardiff. SUBJECTS: 133 babies born consecutively with the use of forceps and 133 control babies born without instrumentation to women matched for parity. INTERVENTIONS: External ocular examination. MAIN OUTCOME MEASURES: The presence within 24 h of birth of corneal oedema, corneal abrasion, conjunctival chemosis, subconjunctival haemorrhage and lid oedema. RESULTS: Lid oedema and multiple minor external ocular trauma occurred in 52 and 22 babies, respectively, in the instrumental delivery group and in 13 and 8 babies, respectively in the control group (P less than 0.001). Corneal abrasion occurred in two babies and corneal oedema in one baby after forceps delivery but in none of the control group. No more serious injuries occurred. All injuries resolved without long term sequelae. CONCLUSION: The frequency of sight threatening corneal trauma in instrumental deliveries is low. Specialist ophthalmic screening of these babies is not justified.

Birth Injuries↗