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Biomedical subjects

A R Morley

Publications and source records attributed to A R Morley.

At least 37 records · Page 2Linked to original sources

Tissue artefacts caused by sponges.

Artefacts which occur during the processing of small biopsy specimens can cause sufficient tissue distortion to impair interpretation and can be a considerable source of nuisance. Triangular artefacts were noted in renal and liver biopsy specimens which were caused by foam sponges in embedding cassettes. Scanning electron microscopic examination of the sponges showed they comprised a mesh of scimitar-shaped rigid spikes which closely match the artefacts seen in the tissues.

Artifacts↗

Immunoperoxidase techniques and histology in the diagnosis of rhabdomyolysis related acute renal failure.

A case of rhabdomyolysis associated acute renal failure (RM-ARF) occurring as a result of strenuous exercise is presented. Diagnostic renal biopsy was performed. The histological appearances, combined with immunoperoxidase staining for myoglobin, allowed a positive diagnosis of RM-ARF to be made and excluded the possibility of glomerulonephritis. The patient recovered completely after a stormy clinical course.

Acute Kidney Injury↗

Corrections in counting paired nuclei labelled with bromodeoxyuridine in tissue sections.

Bromodeoxyuridine is finding increasing use as an alternative to, or in conjunction with, tritiated thymidine for labelling nuclei in DNA synthesis. Precise identification of labelled nuclei is possible, even when there is considerable overlap between neighbouring nuclei. In the sparsely labelled renal cortex of the normal male mouse, 'flash labelling' with bromodeoxyuridine shows single labelled nuclei at 1 h. At 24, 48 and 72 h after injection of bromodeoxyuridine, some labelled cells are seen to lie adjacent and such labelled pairs are presumed to be the result of cell division. Single labelled nuclei at 24, 48 and 72 h might indicate arrest in DNA synthesis or a prolonged G2 period, but it is important to recognize that a correction must be made for paired labelled nuclei in which one member is out of the plane of section. The factors involved in making such a correction are discussed and a correction table calculated. In the normal male mouse renal cortex, we show that nearly all cells labelled at 1 h had divided by 72 h.

Animals↗

Interpretation of biopsies of "normal" urothelium in patients with superficial bladder cancer. MRC Superficial Bladder Cancer Sub Group.

In the course of a Medical Research Council trial of intravesical chemotherapy, biopsies were taken from apparently normal bladder urothelium near to newly diagnosed superficial bladder cancers in 417 patients. Differences were noted in the rates at which histological features were described in different centres. To gain more information about the reproducibility of the pathological findings, a group of 6 pathologists (5 from the UK and 1 from the USA), all having a special interest in urological pathology, were asked to examine a representative sample of 92 slides. They were then asked to re-examine 30 of them after an interval of at least 6 months. At first examination and at re-examination the slides were assessed using a standard proforma. However, the definitions of the categories were left unspecified for the pathologists to use their own criteria. The 5 UK pathologists then met to establish a consensus view of each slide. The results indicated that: (1) The reporting of non-dysplastic changes varied so much between pathologists as to render it of little value to clinical practice. (2) There were wide variations between different pathologists in the reported incidence of dysplastic change. (3) On a second review the pathologists reproduced their own assessment on only 62% of occasions. (4) Even after discussion between pathologists there was no consensus on the diagnosis of mild as opposed to moderate dysplasia. Consensus was reached on all biopsies which showed either severe dysplasia or carcinoma in situ. (5) In adopting a policy of taking urothelial biopsies, urologists should be aware of the imprecision and lack of reproducibility in the interpretation of such biopsies. (6) Biopsies of cystoscopically normal urothelium may not be a useful guide in defining therapy.

Biopsy↗

Three-dimensional reconstruction of juxtaglomerular apparatus (JGA) in five-sixth nephrectomized rats.

In Wistar male rats, hypertension was induced by five-sixth nephrectomy (5/6N). Body weight, systolic blood pressure (SBP) and plasma renin concentration (PRC) were followed for 12 weeks after 5/6N. Three-dimensional reconstruction and morphometry of the JGA were carried out using a computer program "GLOM". Immunohistochemistry and electron microscopy of the JGA were also investigated. A statistically significant increase in SBP was shown after 5/6N. However, PRC showed no increase and was not correlated with SBP. Renin-containing cells were demonstrated in the afferent and efferent arterioles and the interlobular arteries. Electron microscopy revealed granules of various shapes, sizes and electron densities within the JG cell. The frequency of granulated cells in the efferent arteriole was less than that in the afferent arteriole. The afferent arteriole wall volume of 5/6N rats was significantly increased and positively correlated with SBP. The lack of relationship between PRC and SBP in this model suggests that mechanisms other than the renin-angiotensin system may be involved in the pathogenesis of hypertension.

Animals↗

The juxtaglomerular apparatus of the spontaneously hypertensive rat.

Spontaneously hypertensive rats (SHR) are used to study the pathogenesis of essential hypertension. This study investigates the role of the renin-angiotensin system (RAS) in the pathogenesis of hypertension in SHRs and the morphometry of the JGA by a three-dimensional computer reconstruction program "GLOM" and electron microscopy. Systolic blood pressure (SBP) (tail cuff method) was higher in SHRs compared to controls (P less than 0.001). Plasma renin concentration (PRC) was lower in SHRs than in controls (P less than 0.001). Reconstruction of the JGA revealed granulated JG cells in the afferent and efferent arterioles and in the vascular tree away from the JGA area. Electron microscopy showed granulated JG cells in the afferent and efferent arterioles. The percentage volume of the granulated JG cells in SHR was significantly higher than in controls (P less than 0.01). A relationship was found between the percentage volume of granulated JG cells and the SBP in SHRs (r = 0.933, P less than 0.05). The wall/lumen perimeter ratio was also significantly higher in the SHRs compared to the controls (P less than 0.05). Low PRC in SHRs has been reported by several workers. The apparent hyperactivity of the JGA may indicate failure of renin release or an abnormal synthesis/secretion rate.

Animals↗

In vivo bromodeoxyuridine incorporation in normal mouse kidney: immunohistochemical detection and measurement of labelling indices.

A method is reported for in vivo bromodeoxyuridine incorporation in mice and its subsequent visualization in kidney by immunohistochemistry. Following formal-sublimate fixation of the kidney, bromodeoxyuridine labelled nuclei were detected in paraffin sections with a monoclonal antibody and visualized by an immunoperoxidase technique. This rapid and unequivocal method was used to measure labelling indices in tubules, glomerular tuft and Bowman's capsule in normal male T70 (Beige) mice, at intervals up to 72h after labelling. Significant differences were found between the labelling indices of these three populations of cells, which appeared to show different cell kinetic behaviour.

Animals↗

Anti-glomerular basement membrane (GBM) glomerulonephritis in the mouse: development of disease and cell proliferation.

In a mouse model of anti-glomerular basement membrane (GBM) glomerulonephritis, associated with the nephrotic syndrome, a wide range of morphological and proliferative responses was seen in the renal corpuscle, at 6 days. The severity of the damage could be assessed by measuring the average daily weight gain between days 0 and 3 (DWG) of the animal. Those animals with a high DWG showed capsular proliferation, whereas animals with a low DWG showed predominantly tuft cell proliferation. Capsular cell birth rate increased with DWG whilst tuft cell birth rate was negatively related. A computer simulation suggests that the results are compatible with the induction of successive but overlapping waves of tuft and capsular cell proliferation.

Animals↗

Renal vascular disease in diabetes mellitus.

Nephropathy remains a major cause of morbidity and mortality in diabetes mellitus and increasing numbers of patients require dialysis maintenance therapy. Diagnostic criteria of diabetic nephropathy are well established, but the relationship between the morphological changes of glomerular basement membrane thickening and increased mesangial volume and functional abnormalities, such as proteinuria and impaired renal function, are still not clearly understood. Tissue studies in patients with micro-albuminuria, as well as increased knowledge of the structure of the glomerular basement membrane, should lead to an understanding of how the diabetic process affects blood vessels throughout the body.

Basement Membrane↗

Plasma oxalate concentration and secondary oxalosis in patients with chronic renal failure.

To examine the association between hyperoxalaemia and secondary oxalosis, measurement of plasma oxalate concentration was combined with a search for tissue deposition of calcium oxalate crystals in patients with chronic renal disease. Two groups of patients were studied. In the first, samples of the inferior epigastric artery were taken from 35 patients at the time of renal transplantation. In the second, sections taken at necropsy from 23 patients with chronic renal failure in whom plasma oxalate had been measured before death were examined. Though plasma oxalate concentrations ranged between 6 and 116 mumol/l (four to 78 times greater than the upper limit of the reference range), no extrarenal deposits of oxalate were found in either study. Renal deposition of oxalate was associated with a plasma oxalate concentration of greater than 20 mumol/l. This study gives no support to the suggestion that hyperoxalaemia of the degree seen in patients with the type of chronic renal failure that is not due to primary hyperoxaluria confers an appreciable risk of extrarenal oxalosis.

Adolescent↗

Routine and rapid enzyme linked immunosorbent assays for circulating anti-glomerular basement membrane antibodies.

Microtitre plate modifications of the original tube enzyme linked immunosorbent assay (ELISA) of Wheeler and Sussman were used for the routine and rapid assays of anti-glomerular basement membrane antibodies in human sera. In a prospective study of 238 sera from 200 patients, the routine assay (about 24 hours) detected circulating antibodies in seven sera from three patients with active anti-glomerular basement membrane disease. The remaining sera, from patients with a variety of other glomerulonephropathies, were negative by the assay. The rapid assays took less than four hours, and in a retrospective study, detected anti-glomerular basement membrane antibodies in a range of 15 positive sera, with a level of discrimination similar to that observed in the routine assay and with no false positive/negative results.

Antibodies↗

Peri-hilar rupture of Bowman's capsule in crescentic glomerulonephritis.

Crescents are an important structure in many forms of glomerulonephritis and a major cause of destruction of the renal corpuscle. There has been considerable discussion of the cellular content of crescents and of the role of breaks in the glomerular capillary basement membranes. Less attention has been given to abnormalities of Bowman's capsule. We present 2 cases of anti-gbm nephritis showing unusual breaks in Bowman's capsule with a peri-hilar distribution. The mechanisms leading to the rupture of Bowman's capsule are reviewed, as are the possible effect of capsular ruptures on the crescentic cell content.

Adult↗

HLA-A, B, DR and Bf allotypes in patients with idiopathic membranous nephropathy (IMN).

Fifty-five adult biopsy-proven patients with idiopathic membranous nephropathy were examined for HLA-A, B and DR antigens, and for the Bf allotypes. The phenotype frequencies of HLA-DR3 (52 vs. 23%) and HLA-B8 (46 vs. 24%) showed a significant increase in the IMN patient group compared to those of controls from the same region. The supraphenotype in which the combination of DR3-B8 alleles in Bf SS homozygotes occurred was significantly more common in the patient group than in the controls. A subset of six individuals carrying antigens DR3, B8, and common Bf*S alleles was identified, and the clinical course of those patients was found to be significantly worse compared to the rest of the patients. The present results do not support the existing suggestion that the clinical course of these diseases in Caucasians is determined by antigens B18 and the rare Bf allele (Bf*F1). It seems likely that IMN is not a single disease but a renal lesion that can result from several combinations of genetic predisposition and environmental stimuli.

Adult↗

Congenital nephrotic syndrome in Sudan: histological and immunological features.

We report a 5-month-old Sudanese boy with a probable diagnosis of Congenital Nephrotic Syndrome. Our case had features which are neither typical of the Finnish type nor of other hereditary renal diseases. Histologically, the most striking changes were in the glomerular basement membranes which show patchy thinning, thick segments (with reduplication) and occasional low spikes. Tubules are well preserved, and no foam cells were seen. Electron microscopy showed extensive fusion of foot processes with podocyte microvilli. In parts the glomerular basement membrane shows irregular thickening and splitting, and incorporation of podocyte cytoplasm into the membrane. In other areas there is marked thinning of the basement membrane. Immunological features include a high level of IgA and IgG. To our knowledge such features have not been described before.

Basement Membrane↗