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Biomedical subjects

M J Denton

Publications and source records attributed to M J Denton.

At least 37 records · Page 2Linked to original sources

Neurogenic claudication secondary to vascular disease.

Neurogenic claudication is characterized by sensory symptoms which appear during exercise or while maintaining a fixed posture. They are paraesthetic in quality, may be associated with 'march' phenomena, and patients may have bowel and bladder disturbance. The problem is most commonly secondary to lumbar canal stenosis (LCS) but rarely due to aortic disease, as shown in this case report. This report concerns a 66 year old woman who presented with symptoms of paraesthesia radiating from the buttocks to the thigh and, intermittent loss of bladder and bowel function, all associated with walking. There were no associated symptoms of vascular claudication. Clinically, there was evidence of aorto-iliac obstruction with absence of femoral pulses and a vascular index of 0.4 at both ankles. Neurological examination was normal at rest but the left ankle jerk was absent immediately after exercise. Myelogram and computerized tomographic (CT) scan were normal. An aortogram revealed a very tight irregular stenosis of the aorta at the level of the renal and mesenteric arteries. Very few lumbar vessels were seen. An aortic endarterectomy via a thoraco-abdominal approach was performed and an aortobifemoral graft inserted. The patient's symptoms resolved following this procedure. We postulate that her symptoms were caused by a 'steal' from the blood supply to the cauda equinda due to the severe athromatous disease of her upper abdominal aorta.

Aged↗

Therapists' ratings of fundamentalist and nonfundamentalist families in therapy: an empirical comparison.

Using the Family Health Scale, Part I of an instrument developed for this study, two randomly selected groups of certified family therapists rated either nonfundamentalist or fundamentalist families in therapy on eight recognized indicators of family health. Factor analysis yielded eight factors accounting for 66% of the variance between groups. Cannonical discriminant function analysis revealed that therapists rated fundamentalist families as significantly less healthy on three of the eight factors and more healthy on one factor. Part II of this instrument, the Religion Impact Scale assessed the effects of church community and church teachings upon families. For fundamentalists, the church and concomitant belief system had a significant impact upon family organization and functioning. Theoretical and clinical implications of these findings are discussed.

Christianity↗

Description of X-linked megalocornea with identification of the gene locus.

We studied the clinical appearance and inheritance in five families with X-linked megalocornea. Affected male subjects had corneal diameters between 13.0 and 16.5 mm. Arcus juvenilis, mosaic corneal dystrophy, and cataracts were found only in adult affected male subjects. No carrier female abnormality was identified. The gene locus for the X-linked form is in the region Xq12-q26. This is near the locus described for Aarskog (facial-digital-genital) syndrome, Xq12-13.

Chromosome Mapping↗

No evidence of linkage between the locus for autosomal dominant retinitis pigmentosa and D3S47 (C17) in three Australian families.

A linkage analysis has been performed on three Australian families segregating for autosomal dominant retinitis pigmentosa (ADRP). No evidence of linkage has been found in any of the pedigrees studied between the locus D3S47 and the gene for ADRP. The D3S47 locus was found to show very close linkage with the ADRP gene in a large Irish pedigree. Our study together with a similar report on a British family indicates that there is genetic heterogeneity in this disease.

Adolescent↗

Effects of posture and sleep on the pharmacokinetics of paracetamol (acetaminophen) and its metabolites.

The effects of posture and sleep on the pharmacokinetics of paracetamol (acetaminophen) 500 mg and its metabolites were studied in 8 healthy men. The mean residence times for paracetamol or its metabolites were significantly altered by change in posture or by sleep, whereas other pharmacokinetic parameters were unchanged. The change in mean residence time is consistent with a faster absorption of paracetamol during ambulation. The present data suggest that the proposed posture-related changes in volume of distribution do not exist, and that there is no pharmacokinetic basis for a headache being relieved by taking paracetamol and lying down.

Acetaminophen↗

Clinical variability in a family with X-linked retinal dystrophy and the locus at the RP3 site.

One large Australian family with X-linked retinal dystrophy was found to have extreme clinical variability in the hemizygotes. One member had the typical rod-cone disease, three had the cone-rod pattern and one had macroscopic changes in the macular area only, but with low potentials in the ERG. The locus for the disease was found to be distal to L1.28 at Xp21, the site for RP3. From a study of case histories reported it seems that clinical variability can be a common feature of X-linked retinitis pigmentosa (XLRP) with the locus at Xp11.3 (RP2) or at Xp21 (RP3), and this family may well be categorized as XLRP.

Adult↗

Localizing multiple X chromosome-linked retinitis pigmentosa loci using multilocus homogeneity tests.

Multilocus linkage analysis of 62 family pedigrees with X chromosome-linked retinitis pigmentosa (XLRP) was undertaken to determine the presence of possible multiple disease loci and to reliably estimate their map location. Multilocus homogeneity tests furnished convincing evidence for the presence of two XLRP loci, the likelihood ratio being 6.4 x 10(9):1 in favor of two versus a single XLRP locus and gave accurate estimates for their map location. In 60-75% of the families, location of an XLRP gene was estimated at 1 centimorgan distal to OTC, and in 25-40% of the families, an XLRP locus was located halfway between DXS14 (p58-1) and DXZ1 (Xcen), with an estimated recombination fraction of 25% between the two XLRP loci. There is also good evidence for a third XLRP locus, midway between DXS28 (C7) and DXS164 (pERT87), supported by a likelihood ratio of 293:1 for three versus two XLRP loci.

Chromosome Mapping↗

Exclusion of the autosomal dominant retinitis pigmentosa gene from a substantial region of chromosome 1: study of a large Australian family.

In an attempt to map the gene(s) responsible for autosomal dominant retinitis pigmentosa (ADRP), the technique of reverse genetics was used on a large multigenerational Australian pedigree. The family demonstrated a form of the disease which appears to be less severe than that observed in the Irish pedigree. It was typed for 10 restriction fragment length polymorphism (RFLP) markers on chromosome 1. The data from the linkage study was analysed using the programs LIPED 3; six markers gave informative results. The ADRP gene was excluded from this family from 102 cM using previously prepared chromosome 1 maps. This accounts for 36% of chromosome 1 which is estimated to be the longest human chromosome.

Adolescent↗

X-linked megalocornea: close linkage to DXS87 and DXS94.

In a family in which X-linked megalocornea is segregating, the disease locus was found to be closely linked to DXS87 (zeta max = 3.91, theta max = 0.00) and DXS94 (zeta max = 3.34, theta max = 0.00) in Xq21.3-q22.

Corneal Diseases↗

Preliminary exclusion of an X-linked gene in Leber optic atrophy by linkage analysis.

The maternal inheritance in Leber optic atrophy suggests that it may be caused by a cytoplasmic or mitochondrial defect. However, the strong male bias and the strict tissue specificity can not be readily explained by a single mitochondrial gene defect alone. Wallace suggested a hypothesis that the disease could be the result of an interaction between an X-linked gene and a mitochondrial DNA defect. Linkage relationships between Leber optic atrophy and 15 X-chromosome markers were analyzed in three large Tasmanian families. The results of two-point linkage analysis showed no close linkage between Leber optic atrophy and any of the 15 markers. The results of multipoint linkage analysis suggested the exclusion of the assumed X-linked gene from almost the whole X chromosome in these families.

Female↗

Non-allelic mutations in X-linked retinitis pigmentosa.

Using RFLP studies, the disease locus in two X-linked retinitis pigmentosa families was found to be centromeric to DXS7 in one family and telomeric to DXS7 in another, suggesting non-allelic heterogeneity.

Blotting, Southern↗

Analysis of linkage relationships of X-linked retinitis pigmentosa with the following Xp loci: L1.28, OTC, 754, XJ-1.1, pERT87, and C7.

A number of variants of X-linked retinitis pigmentosa (XLRP) have been described. In one variant, listed in the McKusick (McK) catalogue (McKusick 1983) as entry no. 30320, the heterozygotes exhibit a golden metallic or tapetal reflex. Three large pedigrees segregating for XLRP with the characteristic tapetal reflex in the heterozygotes were examined, and the linkage between the XLRP locus and Xp loci, L1.28, OTC, 754, XJ-1.1, pERT87 and C7 was measured. The strongest linkage was found to be between the XLRP locus and OTC. In addition, recombinational evidence drawn from the three pedigrees suggests that the XLRP locus is distal to L1.28 and proximal to 754. This putative location of the XLRP gene between L1.28 and 754 taken together with the tight linkage to OTC, a locus already located between L1.28 and 754, leads us to propose a gene order of centromere-L1.28-OTC/XLRP-754-telomere.

DNA↗

Two different genes for X-linked retinitis pigmentosa.

Linkage analysis was carried out in three large multigenerational kindreds with X-linked retinitis pigmentosa using DNA markers on Xp. About 10% recombination has been found between the retinitis pigmentosa locus (RP2) and the marker locus DXS7, assigned to band Xp11.3, which was reported earlier to be closely linked to RP2 in several independent families. In the kindreds described in this paper, however, RP2 shows close linkage and no recombination with the marker loci OTC and DXS148, both assigned to Xp21, indicating that, contrary to previous linkage studies, there is evidence of an RP locus distal to DXS7. This suggests that X-linked retinitis pigmentosa is genetically heterogeneous, i.e., caused by mutations at different loci.

Female↗

Prenatal diagnosis and carrier detection by DNA studies in a Duchenne muscular dystrophy family with no living affected male.

Restriction fragment length polymorphism studies and gene dosage analysis using the intragenic probes pERT87 were used to detect deletions in potential carriers in a family with Duchenne muscular dystrophy in which the only affected male was deceased. Two females were found to have inherited the paternal pERT87 alleles but not the maternal alleles, suggesting that they have inherited the pERT87 deletion from their mothers. The hybridization signals of pERT87 from these two females upon gene dosage analysis also suggested that they had a single copy of pERT87. The chorionic villi of a male fetus from one of these two females was found to be deleted for pERT87, suggesting that it was affected. This result confirmed the carrier status of the mother.

Alleles↗

Carrier detection in X-pigmentary retinal dystrophy (X-linked retinitis pigmentosa) by DNA restriction fragment length polymorphism studies.

As part of a patient care and DNA research programme commenced in 1985, a number of DNA markers on the short arm of the X chromosome have been used to demonstrate restriction fragment length polymorphisms (RFLPs) segregating with the X-pigmentary retinal dystrophy (X-linked retinitis pigmentosa) gene. The analysis of the segregation of the RFLPs in 3 kindreds enables carrier detection, to a high degree of probability, in females at risk who are not manifesting symptoms and signs.

Adult↗

Extraperitoneal unilateral iliac artery bypass for chronic lower limb ischaemia.

Extraperitoneal unilateral iliac artery bypass was used to treat chronic lower limb ischaemia in 105 patients (110 operations). This represented 20% of all operations for aorto-iliac disease. Unilateral iliac bypass was the preferred primary procedure for 99 operations, and was used to correct complications in one limb of a prior aortic bifurcation graft in the other 11. Ipsilateral femoropopliteal vein grafts were also performed in 45 legs (43%), prior to the iliac bypass in 18, as a synchronous operation in nine, and at a later date in 18 legs. This was a much higher proportion of combined operations than for patients by aortic bifurcation grafts (12%). Only 5 patients later required further proximal surgery, one for a blocked graft and four for contralateral iliac disease. The cumulative patency rate in surviving patients was 91% at 3 years. For the claudicants and for iliofemoral bypass operations, only one graft occluded, within 5 years, and no grafts occluded for operations where the superficial femoral artery was patent. The cumulative patency rates at 3 years were 85% for patients with critical ischaemia, 82% for ilioprofunda bypass operations, and 88% for operations where the superficial femoral artery was occluded. The cumulative foot-salvage rate in surviving patients initially treated for critical ischaemia was 77% at 3 years. The cumulative survival rate was 90% at 3 years. Extraperitoneal unilateral iliac bypass is now preferred as the primary operation for patients with apparent unilateral iliac disease causing severe ischaemia, if balloon dilatation is not appropriate or has failed.

Aorta, Abdominal↗

Experience with DNA analysis in Duchenne and Becker muscular dystrophy families in NSW.

Results of the use of recombinant DNA techniques for the diagnosis of both forms of X-linked muscular dystrophy, Duchenne (DMD) and Becker (BMD), over an 18 month period, are reviewed. In all, 97 families with DMD were investigated and four with BMD. In 90 families the propositi were examined for deletions, in 21 families the maximum number of meioses was examined (in order to generate recombination fraction data) and in 45 families the study was undertaken to provide carrier and prenatal diagnosis.

Chromosome Deletion↗