Biomedical subjects
Publications and source records attributed to S E Pound.
Haplotype analysis was performed in 35 autosomal dominant polycystic kidney disease (ADPKD) families typed with 13 markers close to the PKD1 locus. The identification of recombinants close to the PKD1 gene on chromosome 16p indicates that PKD1 lies between CMM65 distally and 26-6 proximally. In addition, three unlinked (PKD2) families and two families with potential new mutation were identified.
Although dyspeptic symptoms are very common, the vast majority of patients have modest symptoms and rarely seek medical advice. The major organic causes of dyspepsia are chronic peptic ulcer disease, gastro-oesophageal reflux disease and malignancy. Functional dyspepsia is very common. In the fit elderly patient, prompt investigation may be more appropriate than empirical treatment in view of the higher proportion of patients with organic disease and the likelihood of malignancy. The symptoms of peptic ulceration and gastro-oesophageal reflux disease are often atypical in the elderly population. Frail patients, especially those with multiple pathology, should be treated empirically in the first instance. Empirical treatment should be with histamine H2-receptor antagonists or prokinetic agents. Drug treatment is not always required in dyspepsia and should be avoided where possible, especially given the increased risk of drug interactions and poor compliance in the elderly. For those patients with documented non-malignant organic disease, the advent of the H2-receptor antagonists, proton pump inhibitors, prokinetic drugs and regimens which eradicate Helicobacter pylori means that treatment is almost always successful.
The gene for autosomal dominant polycystic kidney disease (PKD1) is located on chromosome 16p, between the flanking markers D16S84 and D16S125 (26.6prox). This region is 750 kb long and has been cloned. We have looked at the association of 10 polymorphic markers from the region, with the disease and with each other. This was done in a set of Scottish families that had previously shown association with D16S94, a marker proximal to the PKD1 region. We report significant association between two CA repeat markers and the disease but have not found evidence for a single founder haplotype in these families, indicating the presence of several mutations in this population. Our results favor a location of the PKD1 gene in the proximal part of the candidate region.
A genetic heterogeneity analysis of 35 kindreds with adult-onset polycystic kidney disease (ADPKD) was carried out using the D16S85, D16S84, D16S125 and D16S94 loci that are closely linked to the PKD1 locus on chromosome 16. The results show that the likelihood of two ADPKD loci is 2,514.9 times greater than for a single locus (P < 0.0001). The maximum likelihood lod score is 27.38 under heterogeneity with PKD1 lying 4.9 cM proximal to D16S85 (in males). At least 3% of kindreds are unlinked to PKD1, since the 95% confidence limits of alpha, the proportion of families linked to PKD1, are 0.54-0.97. Only 2 out of 35 kindreds (5.7%) show statistically significant evidence of non-linkage to PKD1, with conditional probabilities of 0.987 and 0.993 that the disease locus is unlinked. This confirms the existence of a small subgroup of ADPKD kindreds that are unlinked to PKD1 and provides a firm basis for genetic counselling of this population on the basis of DNA probes.
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Analysis of genetic linkage data in 33 adult onset polycystic kidney (ADPKD) families was carried out using probes for the D16S85, D16S84, and D16S94 loci. The data set of 33 families shows no evidence of genetic heterogeneity since one unlinked family was previously excluded. Two point linkage analysis showed maximum likelihood values of the recombination fraction of 0.07 for ADPKD and D16S85 (lod score 18.78), 0.02 for ADPKD and D16S84 (lod score 7.55), and 0.00 for ADPKD and D16S94 (lod score 6.73). Multipoint analysis showed a maximum likelihood order of tel-D16S85-0.06-D16S84-0.02-(PKD1, D16S94)-cen with a multipoint lod score of 32.16. Analysis of rare recombinants lying close to PKD1 gave results consistent with this order.
Fifty-four biopsies of diffuse proliferative glomerulonephritis were subdivided into two groups, diffuse endocapillary proliferative glomerulonephritis (DEPGN) and mesangial proliferative glomerulonephritis (MPGN) according to current morphological criteria. The two groups were then compared by light microscopy, cell counting techniques, electron microscopy, immunofluorescence or immunoperoxidase techniques, and a clinical survey. The results show that DEPGN differs from MPGN in only three points: (1) the former has a greater degree of mesangial proliferation, (2) the former has a less favourable short-term prognosis and (3) large subepithelial deposits (humps) are much more common in DEPGN than in MGPN (in this series no MPGN cases showed such deposits), while small dark deposits are present in or on the glomerular capillary basement membrane in more cases of MPGN than of DEPGN. It is proposed that biopsies showing diffuse proliferation of mesangial cells should be classified as diffuse proliferative glomerulonephritis of a mild, moderate or severe degree, as the current classification has been interpreted as implying separate aetiologies and suggests that these are two distinct disease entities.