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Biomedical subjects

A R Morley

Publications and source records attributed to A R Morley.

At least 55 records · Page 3Linked to original sources

Surface alterations in dialysis roller pump inserts: a scanning electron microscopy study.

Scanning electron microscopy has been used in a study of particle spalling from silicone and PVC elastomer inserts of dialysis roller pumps. In an experimental circuit using Isoton II, pump occlusion, pressure, pump revolutions and temperature were monitored. Scanning electron microscopy was performed on inserts exposed to 1-10 h of pumping using Silastic (medical grade) and a Watson-Marlow MHRE pump, with PVC and Pivipol, a polyurethane coated PVC (Bellco) using a Bellco BL705N pump. Changes included longitudinal splits (single and multiple), superficial cracks (random and orientated), deformations of normal surface pattern, holes, craters and detaching particles. There was an increase in these abnormalities with time for all types of pump insert, the changes being most marked for the Silastic/Watson-Marlow pump combination and least prevalent with the PVC/Bellco pump combination.

Humans↗

Peripheral neutrophil inclusions in amiodarone treated patients.

In 14 patients receiving chronic amiodarone therapy the appearance of multilamellar inclusion bodies in peripheral blood neutrophils was related to both plasma concentrations of amiodarone and its desethyl metabolite and unwanted effects of the drug. Seven of the patients had well defined inclusion bodies. In this group mean amiodarone and desethylamiodarone concentrations were significantly higher than in the remaining seven patients and all but one had unwanted effects of the drug. Of the seven patients without inclusion bodies only one, with high plasma amiodarone and desethylamiodarone concentrations, had unwanted effects of the drug. It is concluded that the appearance of multilamellar bodies in the blood neutrophils of amiodarone-treated patients may help to distinguish those patients at risk of long-term amiodarone toxicity.

Adult↗

Particle spallation induced by blood pumps in hemodialysis tubing sets.

The repeated flexion and compression of pump segments by the rollers of peristaltic pumps results in cracking and abrasion of the inner surfaces of the pump segment, leading to shedding of particles into the extracorporeal circuit. A series of studies to assess the rate of particle release from silicone rubber, polyvinyl chloride (PVC), and Pivipol, a coextruded polyurethane-coated PVC tubing, when these materials were used with blood pumps of the type found in hemodialysis units, was undertaken. The studies show that with all tubing/pump combinations there is an overall increase in the total number of particles released, but an analysis of the particle size distribution indicates that the majority of the particles are less than 16 micron in diameter. The rate of increase may be reduced, however, by decreasing the occlusion pressure.

Analysis of Variance↗

Amiodarone pulmonary toxicity: clinical and subclinical features.

In a prospective study of lung function of 34 patients taking amiodarone, 24 showed no functional changes but 10 developed a sustained fall in CO transfer factor (TLCO) exceeding 15 per cent. These patients had on average received a higher dose of drug in the first three months of treatment. Seven showed no clinical or radiographic changes and TLCO improved with reduction in drug dose. The other three patients developed florid clinical and radiographic features of amiodarone pulmonary toxicity. All three had impaired TLCO before receiving amiodarone. During the course of the prospective study amiodarone pulmonary toxicity was diagnosed in four other patients. Lung tissue was examined in five of the seven patients with clinical toxicity and showed alveolar wall thickening, exudation and interstitial and intra-alveolar fibrosis with prominent 'foamy' macrophages. Electron microscopy of macrophages showed numerous lysosomal multilamellar bodies, which were demonstrated by energy dispersive X-ray analysis to contain iodine, a constituent of the amiodarone molecule. Two of the patients with clinical toxicity died of respiratory failure; the other five showed gradual improvement on withdrawal of the drug and treatment with corticosteroids. Subsequent withdrawal of steroids was associated with clinical and/or functional deterioration in five patients. A separate autopsy study of the lungs of eight patients dying during treatment with amiodarone, but without clinically-recognised toxicity, showed that an alveolitis had been present in two and prominent 'foamy' macrophages were seen in the lungs of six patients. We conclude that clinical and subclinical effects of amiodarone on the lung are common. The clinical syndrome may be easily misdiagnosed as pulmonary oedema. Subclinical changes in lung function are usually reversible, but whether they herald clinical toxicity if treatment is continued without modification is not established. The presence of 'foamy' macrophages may simply reflect exposure to the drug rather than clinically-important toxicity.

Adult↗

Cell proliferation within Bowman's capsule in mice.

Crescentic glomerulonephritis in man, irrespective of aetiology, indicates severe glomerular damage and carries a poor prognosis. The importance of the presence of macrophages in the development of glomerular crescents is well established, but the contribution of cellular proliferation in both macrophages and epithelial cells has received little attention. The purpose of this investigation was to develop a model of crescentic glomerulonephritis in mice, which will be suitable for cell kinetic studies. Preliminary studies are described, involving immunization with rabbit anti-mouse glomerular basement membrane (GBM) antiserum after pre-immunization with rabbit immunoglobulin G, both with and without treatment with a fibrinolytic inhibitor, Cyklokapron. Extensive glomerular damage, with crescent formation, was induced with four daily intravenous injections of rabbit anti-mouse GBM antiserum, after pre-immunization with rabbit IgG. The effect was shown to be dose dependent and was seen within 3 days of the last injection. Linear deposits of rabbit IgG were detected in all glomeruli by immunofluorescence and both linear and granular deposits of mouse IgG were also found. There was a significant increase in glomerular size and in the numbers of cells in Bowman's capsule (P less than 0.01), and increases in mitotic indices to 0.8 per cent were seen by day 13.

Animals↗

Urographic findings in adults with chronic pyelonephritis.

The radiological findings in a cohort of 138 adults with chronic pyelonephritis are presented and the following conclusions made. Scarring is commoner in the right kidney than the left and is found in the upper, middle and lower poles with decreasing frequency from above down. Agreement between observers in the grading of scarring in urograms taken without standardisation or routine tomography, is sufficiently high to justify the continued use of the intravenous urogram as a screening test but is not high enough to detect any progression of scars in the group over a 6.5-year period. Repetition of urograms seldom reveals the development of calculi or other new abnormalities and is not justified as a clinical routine. The combination of extensive bilateral renal scarring and proteinuria is associated with the worst renal function.

Adult↗

Amiodarone and its desethyl metabolite: tissue distribution and morphologic changes during long-term therapy.

The pharmacokinetic characteristics of amiodarone suggest extensive tissue deposition. We confirmed this by measuring tissue concentrations of the drug and of its major metabolite, desethylamiodarone, in human tissues. These were obtained at autopsy (n = 9), surgery (n = 7), or biopsy (n = 2) from 18 patients who had been treated with amiodarone for varying periods of time. High concentrations of amiodarone were found in fat (316 mg/kg wet weight in autopsy specimens, 344 mg/kg wet weight in biopsy specimens). Amiodarone and desethylamiodarone concentrations (mg/kg wet weight, autopsy samples) were also high in liver (391 and 2354), lung (198 and 952), adrenal gland (137 and 437), testis (89 and 470), and lymph node (83 and 316). We also found high concentrations of amiodarone (306 mg/kg wet weight) and desethylamiodarone (943 mg/kg wet weight) in abnormally pigmented ("blue") skin from patients with amiodarone-induced skin pigmentation. These values were 10-fold higher than those in unpigmented skin from the same patients. These high concentrations were associated with lysosomal inclusion bodies in dermal macrophages in the pigmented skin. The inclusion bodies were intrinsically electron dense and were shown to contain iodine by energy dispersive x-ray microanalysis. Lysosomal inclusion bodies shown by electron microscopy to be multilamellar were seen in other tissues. These tissues included terminal nerve fibers in pigmented skin, pulmonary macrophages, blood neutrophils, and hepatocytes and Kupffer cells. These characteristic ultrastructural findings occur in both genetic lipidoses and lipidoses induced by other drugs, e.g., perhexiline. We conclude that during therapy with amiodarone, widespread deposition of amiodarone and desethylamiodarone occurs. This leads to ultrastructural changes typical of a lipidosis. These changes are seen clearly in tissues associated with the unwanted effects of amiodarone, e.g., skin, liver and lung.

Adolescent↗

Haematuria in rheumatoid arthritis: an association with mesangial glomerulonephritis.

Twenty-four patients with rheumatoid arthritis and isolated haematuria were investigated for the cause of their haematuria. In 3 patients local urological disorders were identified, including a pelvicaliceal carcinoma. Renal biopsies were performed on the remaining 21 patients, and the most common abnormality found was a mild mesangial glomerulonephritis (71%). Immunofluorescence and electron microscopy in these patients usually gave normal results. The lesions occurred independently of gold or D-penicillamine therapy and were not associated with impairment of glomerular function.

Adult↗

Idiopathic hypergammaglobulinaemia associated with nephrogenic diabetes insipidus and distal renal tubular acidosis.

Renal tubular dysfunction may be recognized in patients suffering from urinary light chain disease or non-myelomatous hypergammaglobulinaemia. We report a patient who has the combination of distal renal tubular acidosis and nephrogenic diabetes insipidus in association with hypergammaglobulinaemia due solely to increased IgG. We postulate that the abnormalities of distal nephron function resulted from cell-mediated immune damage.

Acidosis, Renal Tubular↗

Isolated C3 deposition in patients without systemic disease.

Deposition of C3 without immunoglobulins ("isolated C3") was found in 9.8% of 540 renal biopsies performed between 1976 and 1982. Thirty-two of these samples were from patients with systemic diseases (16), well defined forms of glomerulonephritis (9), other renal diseases (4) or renal allografts (4). The remaining 22 patients are described. Five had nephrotic syndrome, three of them with minimal changes on light microscopy and good response to corticosteroids. We were left with a group of 17 patients who presented with gross (4) or microscopic (12) hematuria or asymptomatic proteinuria (1) whose biopsies showed mesangial proliferation or/and hyperplasia and who followed a benign course over the mean 3 years of follow-up, with the exception of one whose renal function is declining. This clinicopathological picture is similar to that described in two previous publications suggesting that "Isolated C3 mesangial proliferative nephritis" is a recognizable sub-group within the spectrum of glomerulonephritis.

Adolescent↗

The associations of HLA and other genetic markers with glomerulonephritis.

One hundred and seventy-nine patients with various forms of glomerulonephritis confirmed histologically were tested for HLA A and B antigens: Thirty-four with membranous glomerulonephritis were also typed for DR antigens. One hundred and forty-one of these patients were further tested for blood group, red cell enzyme, and plasma protein systems. The minimal-change and the mesangio-capillary glomerulonephritis showed a significant association with B8 and Bw44 antigens respectively, whereas the membranous nephritis in addition to B8 was also found to be associated with DR3 antigen. Previously described associations with Henoch-Schönlein and Berger's nephritis were not proved. A large group with nonspecific proliferative glomerulonephritis did not show any association with HLA. Among the other single-gene characters studied, a significant association was found with Bf (Factor B or C3 proactivator) and adenosine deaminase, both markers thought to be involved in the immune response. The close association of the markers located on chromosome 6 and glomerulonephritis indicates that there may be an immunological component in the aetiology of the disease. The significance of the various associations found is discussed.

Blood Group Antigens↗

Accumulation of silicone elastomer in regular dialysis.

A retrospective autopsy study of 78 patients treated by some form of dialysis for chronic renal failure in Newcastle 1964-1981 showed that: 1) Particles resembling silicone elastomer were present in 48 per cent of 61 patients haemodialysed with the use of silicone rubber pump inserts but in none of the 11 treated by haemodialysis with other pump inserts or of the six treated by peritoneal dialysis alone; 2) The prevalence of these particles and their density increased with time on haemodialysis; 3) There was little evidence of a tissue reaction to the particles and no association between their presence and histological evidence of liver disease; 4) There was a higher incidence of clinical and biochemical evidence of liver disease in patients with silicone deposits than in those without. Although there are other possible explanations for this higher incidence of hepatic dysfunction it would be safer to assume that silicone particle spallation is not innocuous.

Humans↗

Renal biopsy appearances in rheumatoid disease.

The renal biopsies of 30 patients with rheumatoid arthritis and clinical evidence of renal disease were reviewed; only patients in whom the intravenous pyelogram was normal were subjected to biopsy, thus excluding those with papillary necrosis and chronic pyelonephritis. Tissue was studied by light, electron and immunofluorescence microscopy. There were 13 cases of mesangial change, 9 of membranous glomerulonephritis, 4 of tubulointerstitial change, 2 cases of focal segmental glomerulosclerosis, 1 case of amyloid and 1 of diffuse proliferative glomerulonephritis with crescents. All 9 patients with membranous glomerulonephritis but only 6 of 13 with mesangial change had received gold or penicillamine. We found no evidence of "glomerulitis" or of a rheumatoid vasculitis.

Adult↗

Serum immunoglobulins in minimal change nephrotic syndrome--a possible defect in T-cell function.

Serum immunoglobulin concentrations were determined in eighteen patients with minimal change nephrotic syndrome. Serum IgG and IgA were significantly decreased; whereas IgM was significantly increased in majority of the cases. Eight of the eighteen patients were treated with steroids. All the eight patients showed a significant increase in serum IgG and a decrease in IgM in response to steroid therapy. The increased serum IgM and decreased IgG before treatment and their restoration to normal levels after steroid therapy may suggest a possible defect in T-cell function.

Adolescent↗