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D A Aitken

Publications and source records attributed to D A Aitken.

At least 55 records · Page 3Linked to original sources
PubMed1994

An ultrastructural investigation of an early manifestation of the posterior polymorphous dystrophy of the cornea.

BACKGROUND: Posterior polymorphous dystrophy of the cornea is an uncommon, but well-recognized, congenital disease affecting Descemet's membrane and endothelium. Visual impairment usually is minimal and slowly progressive. Edema develops in a small number of patients, necessitating a corneal graft in middle age. An early manifestation of posterior polymorphous dystrophy with corneal edema present at birth or soon thereafter is extremely rare; only a few ultrastructural reports are available. METHODS: The corneal button of a 5-month-old baby with posterior polymorphous dystrophy was examined by conventional light and electron microscopy. FINDINGS: The anterior banded zone of Descemet's membrane was thinned (2 microns) in the axial part of the cornea, contained defects in the paraxial part, and was absent at the periphery. Where present, the anterior banded zone was lined posteriorly by a fibrocellular layer (containing fibroblast-like spindle cells and striated collagen fibrils) and a fibrillar layer forming an abnormal posterior collagenous layer. This layer was lined posteriorly by degenerate overlapping endothelial cells, which also were in apposition to the stroma in regions with an absent anterior banded zone. The defects in Descemet's membrane were used by the abnormal keratocytes to migrate between the anterior banded zone and the posterior collagenous layer. At the periphery, a multilayer of spindle cells was present behind the stroma. CONCLUSIONS: Failure to produce a continuous anterior banded zone indicates an onset of the disease before the twelfth week of gestation. It appears that, in posterior polymorphous dystrophy, there is a mosaic of better preserved and dystrophic endothelial cells and that the presence or absence of the normal components of Descemet's membrane is determined by the proportion of dystrophic cells in the endothelial cell population.

Consanguinity↗
PubMed1994

Acute bilateral optic disc neovascularization.

PURPOSE: A case of bilateral acute neovascularization of the optic disc and peripapillary epiretina of unknown etiology in a previously healthy 26-year-old woman is discussed. METHODS: The clinical course of the disease, investigation, and treatment are presented in detail. RESULTS: Histopathologic examination of epiretinal tissue removed from the second eye at vitrectomy provided evidence of inflammatory disease and suggested a possible etiology. CONCLUSION: The cause of this patient's disease remains uncertain. Known causes of this disease were excluded as far as possible. Histopathologic examination of the epiretinal membrane from the second eye demonstrated an unusually increased inflammatory response and multiple intracytoplasmic inclusion bodies in neutrophils resembling mollicute-like organisms.

Acute Disease↗
PubMed1994

First trimester biochemical screening for trisomy 21: the role of free beta hCG, alpha fetoprotein and pregnancy associated plasma protein A.

The potential efficacy of screening for trisomy 21 in the first trimester, using maternal serum markers alpha fetoprotein, free beta human chorionic gonadotropin, unconjugated oestriol and pregnancy associated plasma protein A, was studied in an unselected population of women between the seventh and fourteenth week of gestation. Using a combination of alpha fetoprotein and free beta human chorionic gonadotropin, 53% of affected pregnancies could be identified at a false positive rate of 5%. Unconjugated oestriol and pregnancy associated plasma protein A levels were lower in cases of trisomy 21, but their inclusion with other markers did not significantly improve detection rate. Monitoring the same pregnancies also in the second trimester showed that screening in the first trimester identified the same cases as in the second. We conclude that first trimester screening using free beta human chorionic gonadotropin and alpha fetoprotein, is a viable possibility and will lead to detection rates in excess of 50%. Prospective studies are needed to confirm these observations.

Adolescent↗
PubMed1994

Impact of a regional screening programme using maternal serum alpha fetoprotein (AFP) and human chorionic gonadotrophin (hCG) on the birth incidence of Down's syndrome in the west of Scotland.

OBJECTIVES: To evaluate the impact of a large scale population screening programme on the birth incidence of Down's syndrome in the west of Scotland over a 12 month period. METHODS: Biochemical screening for Down's syndrome using maternal serum alpha fetoprotein, chorionic gonadotrophin, and maternal age was offered to a pregnant population of 37,226 women in the west of Scotland between 1991 and 1992. The combined risk of Down's syndrome pregnancy was reported for each of the 30,084 women who opted for screening. RESULTS: When a threshold risk of 1:220 was used 1523 women (5.1% of the screened population) were assigned to the high risk group, of whom 1070 (70%) proceeded to diagnostic amniocentesis or midtrimester chorionic villus sampling. When multiple sources of ascertainment were used 37 Down's syndrome pregnancies were identified within the screened population, 26 (70%) of which were within the high risk group and 21 (57%) of which were prenatally diagnosed. In addition, three Down's syndrome pregnancies were diagnosed by first trimester chorionic villus sampling before biochemical screening. A further 10 Down's syndrome pregnancies were identified at birth, eight to women who had not had a screening test and two to women who had moved into the area, making a total of 50 Down's syndrome pregnancies in the whole pregnant population of 37,226. Thus the potential prenatal detection rate in the screened population was 70% (26/37), the actual prenatal detection rate in the screened population was 57% (21/37), and the overall prenatal detection rate in the total (screened and unscreened) population was 48% (24/50). CONCLUSION: Biochemical screening for Down's syndrome is practical and effective in routine clinical practice, enabling women to make an informed choice about prenatal diagnosis and providing better use of scarce resources when a suitable protocol is applied to the whole pregnant population. Its maximum potential for the reduction of the birth incidence of Down's syndrome is limited by incomplete uptake of screening and compliance with diagnostic testing in the high risk group.

Adolescent↗
PubMed1994

Multirecurrence of corneal posterior polymorphous dystrophy. An ultrastructural study.

Posterior polymorphous corneal dystrophy (PPD) is a rare bilateral, autosomal-dominant disease. The presence of the epitheliumlike endothelium and the thickening of Descemet's membrane by the posterior collagenous layer (PCL) has been reported in the majority of published cases. Reepithelialization of the posterior cornea in donor tissue has been reported only once. Therefore, to examine this process we examined, by light and electron microscopy, three corneal buttons (an original and two subsequent keratoplasties after 3 and 4 years, respectively) from the left eye of a patient with bilateral disease. Our study showed a repopulation of the posterior surface of the donor corneas by the host epitheliumlike endothelium, which was of identical morphology in each case. In contrast to the previously published work, a posterior collagenous layer in the failed grafts was absent from the axial cornea, where the epitheliumlike endothelium was in direct contact with donor Descemet's membrane. A PCL at the periphery in the failed transplants was of the fibrocellular type and differed from the fibrillar PCL in the first keratoplasty specimen. The fibroblastlike cells within the fibrocellular PCL were distinct from the underlying epithelial-like cells and contained numerous tertiary phagolysosomes. We suggest that the major contributor to the fibrocellular PCL in the repeat keratoplasties was a fibrous ingrowth from the host/graft junction and not the epitheliumlike endothelium. It appears that the synthetic capacity of the epitheliumlike endothelium was similar to that of the normal epithelium and was much lower than that of normal native endothelium.

Corneal Dystrophies, Hereditary↗
PubMed1993

Second-trimester unconjugated oestriol levels in maternal serum from chromosomally abnormal pregnancies using an optimized assay.

Second-trimester unconjugated oestriol (UE3) levels were measured retrospectively in maternal serum from 78 chromosomally abnormal pregnancies and 390 matched controls using a radioimmunoassay kit (Amersham AMERLEX-M) optimized for use in the second trimester. Reduced levels of UE3 were found in a group of 49 Down's syndrome pregnancies with a median UE3 level of 0.79 multiples of the median (MOM) of the controls. Four trisomy 18 pregnancies had UE3 levels less than 0.7 MOM. There was a highly significant level of correlation between alpha-fetoprotein (AFP) and UE3 levels in the controls (r = 0.25, p < 0.01), the Down's syndrome pregnancies (r = 0.44, p < 0.01), and the other chromosome abnormalities (r = 0.61, p < 0.01). When used as an additional marker to AFP and human chorionic gonadotrophin in screening for Down's syndrome, UE3 does not appear to add to the sensitivity of such screening.

Chromosome Aberrations↗
PubMed1993

First-trimester biochemical screening for fetal chromosome abnormalities and neural tube defects.

Alpha-fetoprotein (AFP), unconjugated oestriol (UE3), intact human chorionic gonadotrophin (intHCG), and the free beta subunit of chorionic gonadotrophin (F beta HCG) were investigated in a series of 21 chromosomally abnormal and 14 open neural tube defect pregnancies ascertained from a series of 14,000 prospectively collected maternal serum samples at 6-14 weeks' gestation. In 16 cases of Down's syndrome, significant reductions were found for AFP (0.65 multiples of the normal median) and UE3 (0.67 MOM). IntHCG levels were unaltered (0.97 MOM) but a significant increase was found for F beta HCG (1.96 MOM). Significant correlations were found for AFP and UE3 in the controls and for intHCG and F beta HCG in both the control and the Down's syndrome pregnancies. In a group of five trisomy 18 pregnancies, median MOMs were for AFP 0.71, for UE3 0.34, for intHCG 0.27, and for F beta HCG 0.15. None of 13 pregnancies with open neural tube defects at 8-13 weeks gestation had elevated maternal serum AFP levels, whereas matched second-trimester samples from the same pregnancies at 16-18 weeks gestation all had significantly elevated AFP levels. Thus, biochemical screening for chromosome abnormalities may be practicable in the first trimester using free beta human chorionic gonadotrophin in combination with AFP and maternal age. However, a separate screening protocol using AFP at 15-18 weeks gestation would still be required for effective detection of neural tube defects.

Biomarkers↗
PubMed1993

Dual analyte immunoassay in neural tube defect and Down's syndrome screening: results of a multicentre clinical trial.

We report a multicentre clinical field trial of a novel dual analyte enzyme immunoassay method for the simultaneous measurement of alpha-fetoprotein (AFP) and free beta-human choriogonadotropin (hCG) in the same microtitre well. The assay was shown to have good technical performance in the hands of all trial centres, with between assay coefficients of variation better than 10% for both analyte across the whole of the assay ranges. The method compared well with single analyte measuring procedures and produced acceptable performance as judged by external quality assurance criteria. Recovery of added analyte and analyte dilution curves also showed acceptable performance. In clinical evaluation of a large set of neural tube defect cases, good clinical discrimination from unaffected cases was observed using AFP. With over 150 Down's syndrome cases, the combination of AFP and free beta hCG confirmed the high detection rates achievable using this marker combination, with detection rates in excess of 70% in early gestation. We conclude that the combination of clinically superior markers coupled with technologically innovative assay design will lead to more efficient Down's screening programmes.

Adolescent↗
PubMed1992

Variation in the levels of pregnancy-specific beta-1-glycoprotein in maternal serum from chromosomally abnormal pregnancies.

Human pregnancy-specific beta-1-glycoprotein (SP1) was assayed retrospectively in stored maternal serum (MS) samples from 82 chromosomally abnormal pregnancies and 377 matched controls. The median MSSP1 concentration in 48 Down's syndrome pregnancies was significantly elevated at 1.17 multiples of the control median (MOM), and significantly reduced (0.5 MOM) in a group of eight cases of unbalanced translocations. There was no significant difference in median SP1 concentrations in cases of trisomy 18, trisomy 13, balanced translocations, or sex chromosome abnormalities. A comparison with human chorionic gonadotrophin results in the same series of samples indicates that SP1 is a less sensitive predictor of Down's syndrome pregnancies.

Chorionic Gonadotropin↗
PubMed1991

Prenatal screening for chromosome abnormalities using maternal serum chorionic gonadotrophin, alpha-fetoprotein, and age.

Human chorionic gonadotrophin (hCG) levels were assayed retrospectively in stored maternal serum samples from 78 chromosomally abnormal pregnancies and 410 controls matched for gestation and maternal age. The median serum hCG concentration in 49 pregnancies with Down's syndrome was significantly elevated, at 2.18 multiples of the normal median. Significantly reduced hCG concentrations were found in a group of four trisomy 18 pregnancies (all less than 0.4 multiples of the median). Eight cases of unbalanced chromosome rearrangements appeared to show some lowering of hCG levels, while there was no significant difference in the levels in the cases of trisomy 13, balanced translocations, and sex chromosome abnormalities. Maternal serum hCG alone is a better indicator of Down's syndrome pregnancies than maternal age or maternal serum alpha-fetoprotein (AFP), either individually or in combination, and provides a further virtually independent measure of risk. On the basis of our findings, screening for Down's syndrome using hCG and AFP results combined with maternal age risks is predicted to result in a higher detection rate (57 per cent) for a lower false-positive rate (5.0 per cent) than would be attainable by combined AFP and age screening (37 per cent detection at a 6.6 per cent false-positive rate).

Chorionic Gonadotropin↗
PubMed1991

Estimating the risk of a fetal autosomal trisomy at mid-trimester using maternal serum alpha-fetoprotein and age: a retrospective study of 142 pregnancies.

Risks appropriate for mid-trimester prenatal screening for autosomal trisomies have been estimated from a combination of maternal age and maternal serum (MS) alpha-fetoprotein (AFP) levels at 16-20 weeks gestation. Published data on the frequency of Down's syndrome births relative to maternal age were modified to include the additional age-related frequency of trisomy 18 and trisomy 13 cases to provide an overall risk for an autosomal trisomy at mid-trimester. MSAFP results from a retrospective study of 142 affected (114 trisomy 21, 19 trisomy 18, and 9 trisomy 13) and 113,000 unaffected pregnancies were converted to multiples of the appropriate gestational median (MOM). The AFP levels in the autosomal trisomy pregnancies were found to be significantly reduced at 0.72 MOM of the unaffected pregnancies. Risks (likelihood ratios) were derived from the overlapping log Gaussian distributions for affected and unaffected pregnancies and combined with maternal age risks to give the overall odds of an affected pregnancy. A mid-trimester cut-off risk of 1:280 gave an estimated 37 per cent detection rate for autosomal trisomies in the west of Scotland population for a follow-up (false-positive) rate of 6.6 per cent. These figures compare with a 30 per cent detection and 6.7 per cent false-positive rate if age 35 years and over is used as the sole criterion for selection of at-risk pregnancies.

Adolescent↗
PubMed1990

Trisomy 20q caused by der (X)t(X;20)(q28;q11.2).

A first case of "pure" trisomy 20q (q11.2-qter) is described in a female child with minor anomalies and developmental delay. This resulted from the inheritance, from a carrier mother, of an abnormal X chromosome: der (X)t(X;20)(q28;q11.2). Involvement of other autosomes has complicated the interpretation of the phenotypic effect of trisomy 20q in previously published case reports. Red cell gene dosage studies using adenosine deaminase (ADA) have confirmed that the proposita is trisomic for 20q. Taken together with RBG staining studies, these results suggest that there is incomplete inactivation, if any, of the autosomal portion of the consistently late-replicating abnormal X. Unexpectedly, ADA gene dosage results in the carrier mother showed a level of gene expression about half that of normal controls.

Chromosomes, Human, Pair 20↗
PubMed1989

Amniotic fluid alpha-fetoprotein, gamma-glutamyltranspeptidase, and autosomal trisomies.

Alpha-fetoprotein (AFP) concentration and gamma-glutamyltranspeptidase (GGT) activity have been analysed in amniotic fluid from a series of 65 pregnancies with autosomal trisomies. AFP values were reduced on average to 60 per cent of normal in cases of trisomy 21, but were not significantly different from normal in cases of trisomies 18 and 13. GGT activities were uniformly lower (44 per cent of normal) for all types of autosomal trisomy. A review of the literature indicates that over 85 per cent of Down's pregnancies but only 39 per cent of trisomy 18 and 13 pregnancies have amniotic fluid AFP levels below the normal median value, while the corresponding figures for GGT are 91 per cent for Down's syndrome and 96 per cent for trisomies 18 and 13.

Amniotic Fluid↗
PubMed1988

X chromosome deletions detectable by flow cytometry in some patients with steroid sulphatase deficiency (X-linked ichthyosis).

The X chromosomes of individuals with isolated steroid sulphatase deficiency (X-linked ichthyosis) from ten families were studied by flow karyotype analysis. In four of the families, a small but significant reduction in the relative fluorescence of the X chromosome was detected consistent with a deletion ranging from 1.2%-3.4% of the X and amounting to a DNA loss of 1.9-5.2 million base pairs. In the remaining six families, three of which demonstrated a molecular deletion of the DNA sequence GMGX9 (DXS237), the relative fluorescence of the X chromosomes was indistinguishable from normal. The phenotypes of those with X deletions detectable by flow cytometry were similar to those of patients without such deletions.

Chromosome Deletion↗
PubMed1987

Deletion of a DNA sequence in eight of nine families with X-linked ichthyosis (steroid sulphatase deficiency).

Deficiency of steroid sulphatase (STS) is associated with ichthyosis, with failure of the placental production of oestriol in late pregnancy and with difficulties in childbirth. The STS gene has been localised by deletion mapping to the distal tip of the snort arm of the X chromosome, and is of interest in that it appears to escape X-inactivation. We have constructed an X-specific DNA library and screened it for single copy DNA sequences which lie at the distal end of Xp. The sequence GMGX9 was found to map in the interval Xp22.3-pter and to detect a frequent HindIII polymorphism. We have used GMGX9 in linkage studies in families with classical X-linked ichthyosis and this has not only shown tight linkage with STS deficiency but has also revealed that the sequence is deleted in affected males in eight of nine families. GMGX9 is present in all of 26 normal male individuals so far examined. Our findings suggest that a high proportion of the mutations at the STS locus leading to enzyme deficiency are deletions, presumably generated by unequal cross-over events in female meiosis or by illegitimate X-Y interchange in male meiosis.

Base Sequence↗