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Biomedical subjects

M K MacDonald

Publications and source records attributed to M K MacDonald.

At least 19 recordsLinked to original sources

Fundus changes in (type II) mesangiocapillary glomerulonephritis simulating drusen: a histopathological report.

We report for the first time to our knowledge the histopathological findings in the eye of a patient with type II mesangiocapillary glomerulonephritis (dense deposit disease) in which a deposit of material morphologically very similar to that which is pathognomonic for the disease in the kidney was demonstrated in Bruch's membrane. The nature of the deposit in the renal lesion is unknown but is considered to represent a structural alteration secondary to a reaction with anticomplement antibody. Clinically the fundus appearance resembled that seen in drusen.

Adolescent↗

Mefenamic acid nephropathy: an interstitial and mesangial lesion.

Six cases of acute renal failure associated with mefenamic acid therapy are described. Five patients were non-oliguric and five patients had clinical features of salt and water depletion. In these patients the presenting symptoms were abdominal pain, diarrhoea and vomiting. Renal biopsy in five patients showed interstitial nephritis and mesangial proliferation. All patients recovered without specific therapy after withdrawal of the drug, but in four patients mild renal impairment persisted. These findings indicate that both interstitial and mesangial changes are common features of acute renal failure due to mefenamic acid therapy.

Adult↗

Diffuse proliferative glomerulonephritis--how many types?

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.

Biopsy↗

The origin of cells in the glomerular crescent investigated by the use of monoclonal antibodies.

A study was made of the cells forming the crescents in human crescentic glomerulonephritis. The investigation was performed using a panel of antibodies with immunoperoxidase techniques in formalin fixed, paraffin embedded renal biopsy material. Some of the cells of glomerular crescents were found to contain cytokeratin intermediate filaments, as did some of the cells of the normal parietal epithelium of Bowman's capsule. Leucocytes were also found in crescents, often in the outer part, and their presence was associated with a mantle of inflammatory cells around the glomerulus. The use of paraffin embedded rather than frozen tissue allowed better histological assessment than has been possible in previous studies. The glomerular crescents appeared to be primarily epithelial in origin, with leucocytes contributing to the overall inflammatory response.

Antibodies, Monoclonal↗

Membranous glomerulonephritis.

In a clinicopathological survey of idiopathic membranous glomerulonephritis (MGN) in 85 patients the predominance of the condition among men could be at least partly explained by an increased risk of exposure to organic solvents and heavy metals in the course of work. This may have implications for the advice given to these patients after MGN has been diagnosed. The selectivity of proteinuria could predict the likely outcome of the disease.

Adolescent↗

Incidence of intraglomerular platelets in steroid sensitive nephrotic syndrome.

Renal biopsies from 44 patients with steroid sensitive nephrotic syndrome were examined with respect to the content of their intraglomerular platelets and compared with 18 normal control patients and with 51 patients with membranous glomerulonephritis and the nephrotic syndrome. The results suggested that platelet activity was not involved in the pathogenesis of steroid sensitive nephrotic syndrome; in the active phase of the number of platelets in glomeruli is lower than that of normal controls, and this may be associated with increased sensitivity to aggregating agents as part of the nephrotic syndrome. After steroid treatment and disappearance of proteinuria, the number of intraglomerular platelets rises to normal values.

Adolescent↗

Proliferative glomerulonephritis and exposure to organic solvents.

Exposure to organic solvents was compared by interview and questionnaire in 50 patients with biopsy-proven proliferative glomerulonephritis in whom there was no evidence of systemic disease or preceding infection with that of 100 control subjects matched for age, sex and social class. The interview was conducted by a lay person who did not know whether the interviewee was a patient with glomerulonephritis or a control subject. The exposure scores derived from the results of the questionnaires were significantly greater in the patients with glomerulonephritis than the control subjects (13,186 +/- 3,716 vs. 3,030 +/- 1,152, p less than 0.01). The degree of exposure was higher in those patients with the more severe diffuse endocapillary proliferative glomerulonephritis than in those with mesangial proliferative glomerulonephritis. In the glomerulonephritis patients solvent exposure was mainly occupational in origin and involved fuels, paints and degreasing agents in most cases. This occupational exposure was significantly greater than in the control subjects (13,061 +/- 3,858 vs. 2,878 +/- 1,146, p less than 0.01). It is suggested that exposure to organic solvents may participate in the pathogenesis of non-systemic proliferative glomerulonephritis.

Biopsy↗

Histological and ultrastructural studies of the human juxtaglomerular apparatus in benign and malignant hypertension.

The light and electron microscopic appearances of the human juxtaglomerular apparatus in benign essential and malignant (accelerated phase) hypertension are described. In the former, the variability of appearances precludes assessment of the importance of the apparatus in the pathogenesis or progression of the disease. The hyperplastic appearance of the apparatus in malignant hypertension supports the concept of renin hypersecretion in this phase. Mechanisms of JGA stimulation are considered and the possibility of a new source of renin discussed. It is suggested that morphological appraisal of cellular activity could be correlated with chemical estimations, allowing a clearer delineation of the role of the renin-angiotensin system in the pathogenesis and progression of benign and malignant hypertension. This might be of value in assessing the cellular response to various specific pharmacological agents used in the management of these conditions.

Adult↗

Mesangiocapillary glomerulonephritis: a long-term study of 40 cases.

Forty cases of mesangiocapillary glomerulonephritis are reviewed for whom both light and electron microscopy and full clinical data were available. Immunofluorescence microscopy (IF) was performed on 23 cases and complement screening (CH50, C4 and C3) on 25 cases, with follow-up period of 5-22 y. The results of EM revealed 17 cases (42 per cent.) of Type I and 23 cases (58 per cent.) of Type II MCGN but only 52 per cent. of Type II cases were correctly identified by light microscopy. Epimembranous deposits were seen as frequently in Type II as in Type I (26 per cent. and 30 per cent.) and fragmentation of glomerular capillary basement membranes (GBM) was seen in 27 per cent. of Type I cases. Overall patient survival was 49 per cent. at 10 y and that of patients who presented with nephrotic syndrome was poor (39 per cent. at 10 y). Persistent hypocomplementaemia with C3 Nephritic Factor was present in 40 per cent.; the survival of these patients was less than those with normal complement levels (70 per cent. vs 100 per cent. at 5 y) and they were also more likely to develop renal failure. Renal failure was more likely to develop in those with a creatinine clearance of less than 100 ml/min at presentation and where the biopsy showed substantial crescents in greater than 20 per cent. of glomeruli. Mean CH50, C3 and C4 was lower in the hypocomplementaemic as compared to normocomplementaemic patients, and there were no differences between Type I and Type II. IF showed immunoglobulins and fibrin as well as C3 in both Type I and Type II cases. Our results support the concept of an immune-complex mediated phase in both types of MCGN, and we further suggest that (a) epimembranous deposits are common in both Type I and Type II and (b) cases with fragmentation of the GBM should be designated Type Ia.

Adolescent↗

Histological and ultrastructural studies of the human juxtaglomerular apparatus in Bartter's syndrome and renal artery stenosis.

Histological and ultrastructural studies of the juxtaglomerular apparatus (JGA) were performed on renal biopsy material from three cases of Bartter's syndrome and two cases of renal artery stenosis. These cases of known JGA hyperfunction were compared with the apparatus in a presumed inactive or basal state as in minimal lesion glomerulonephritis. Light microscopic assessment of the ease of JGA identification, its size and cellularity, provides a valuable reflection of activity and indicates those cases which require ultrastructural assessment of granule turnover. Granule stains often failed to demonstrate any significant increase in granule number in the two conditions studied, and only ultrastructural studies allowed evaluation of secretory activity, rhomboid granule formation and granule release. From these investigations, a proposed mechanism of granule turnover is suggested. The morphological findings in both Bartter's syndrome and renal artery stenosis support the concept of hyperfunction of the apparatus. They may help to elucidate the pathogenesis of Bartter's syndrome and to predict the outcome of surgical intervention in renal artery stenosis. Such studies could profitably be performed on renal biopsies in other disease states, so augmenting our understanding of the contribution of the JGA to the pathogenesis of a variety of glomerular and vascular lesions.

Bartter Syndrome↗

Poisoning by Cortinarius speciosissimus.

Severe renal failure caused by the mushroom Cortinarius speciosissimus was first recognised in 1972 and has been reported only from Scandinavia. In the summer of 1979 and following the consumption of the wild mushroom in Scotland, three previously healthy young adults developed the recognised features of cortinarius poisoning-namely, gastrointestinal upset after 36-38h, followed by nausea, anorexia, headache, rigors, severe burning thirst, muscle aching, and oliguria. One patient had a diuresis after 8 days and recovered completely. The two other patients did not present to hospital until 10 days after ingestion and severe renal failure had already developed. Both had a severe interstitial nephritis and neither recovered renal function. They were maintained on intermittent haemodialysis until they received renal transplants 9 months later. This form of mushroom poisoning has not so far been reported in the British Isles. With the increasing popularity of wild-mushroom eating, posters and publications on wild edible foods should contain warnings about the toxic nature of species of the genus Cortinarius.

Adult↗

Uptake and transport of Imposil by the glomerular mesangium in the mouse.

The mesangial uptake and transport of particulate material has been studied using an iron-dextran complex, Imposil, as a tracer particle. The tracer was given as a single dose into the tail vein of the mouse, and animals were killed at intervals from 5 minutes to 48 hours. Light and electron microscopy showed that the iron-dextran complex was initially taken into the matrix channels of the mesangium from which it progressed over the course of 8 hours to the matrix of the juxtaglomerular apparatus and intercellular spaces of the macula densa. This delineated a continuous functional pathway from the glomerular capillary lumen to the macula densa cells of the distal tubule for material taken up by the mesangium. It is suggested that the products of inflammatory lesions in the glomerulus could affect the secretory function of the granular cells of the juxtaglomerular apparatus as it would appear that such products must circulate in the immediate environment of these cells.

Animals↗

The role of the mesangial cell in proliferative glomerulonephritis.

In 40 patients with a histological diagnosis of proliferative glomerulonephritis the deposition of immunoglobulins, complement (C(3)), and fibrin/fibrinogen has been assessed by immunofluorescence and electron microscopy. The results of such examinations have been correlated with the outcome of the illness. In minor or resolving disease there is usually minor functional impairment, a good response to therapy or spontaneous resolution, the deposition of small amounts of material in glomerular capillary walls, and active mesangial removal. In moderate to marked disease there is initially a moderately severe functional disorder, a good response to therapy, considerable deposition of material in glomerular capillary walls but with less active mesangial regions than in the previous group. In progressive glomerulonephritis there was initial severe functional disorder, poor response to therapy, large amounts of material deposited within capillary walls, and active mesangial regions which were greatly enlarged, containing numerous deposits. In the rapidly progressive group there was severe functional disorder with poor response to therapy, the deposition of only small amounts of material within capillary walls, the lack of any significant mesangial cell reaction, and the formation of epithelial crescents. The results of the study indicate that in proliferative glomerulonephritis following the deposition of material in glomerular capillary loops, the progression of the disease is, to some extent at least, dependent upon the ability of the mesangial cell to remove such material.

Adolescent↗