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Biomedical subjects

D Adu

Publications and source records attributed to D Adu.

At least 91 records · Page 5Linked to original sources

Increased prevalence of renal biopsy findings other than diabetic glomerulopathy in type II diabetes mellitus.

It is a widely held view that when a patient with type I diabetes mellitus and diabetic retinopathy or neuropathy develops renal impairment the renal lesion will be diabetic glomerulonephropathy. This has been extrapolated to apply to type II diabetes. We have performed a retrospective study of the clinical data of patients with diabetes mellitus who have had a renal biopsy between November 1980 and December 1990. Seventy-one patients were biopsied, data were available on 68. Nineteen of 22 type I diabetics had diabetic glomerulopathy, two had diabetic glomerulopathy in addition to another lesion only one patient did not have diabetic glomerulopathy. Twenty-three of 46 type II diabetics had diabetic glomerulopathy alone 22 having an alternative diagnosis. Eight further patients were identified who were not known to be diabetic at the time of renal biopsy, but whose biopsies revealed diabetic glomerulopathy. These data suggest that patients with type II diabetes and renal impairment should have a renal biopsy as part of their investigation.

Adult↗

Endothelium myeloperoxidase-antimyeloperoxidase interaction in vasculitis.

Antibodies to myeloperoxidase (MPO) are found in the sera of patients with microscopic polyarteritis and idiopathic crescentic glomerulonephritis. Their pathogenicity is unknown. Studies were carried out on the binding of MPO to cultured human umbilical vein endothelial cells and the recognition of endothelium-bound MPO by antibody to MPO. Endothelial cells were cultured from human umbilical veins. The binding of MPO to endothelial cells and its inhibition by poly-D-lysine was detected using a monoclonal antibody to MPO and direct staining with APAAP and also by an enzyme-linked immunoassay (ELISA). The binding of anti-MPO antibody in the sera of patients with microscopic polyarteritis to endothelium-coated MPO was detected by ELISA. MPO bound to endothelial cells both on direct staining and ELISA and this binding was inhibited by the polycation poly-D-lysine, suggesting that it was charge mediated. Binding of anti-MPO antibody in the sera of patients with microscopic polyarteritis to endothelium-coated MPO was significantly higher than the binding of sera from normal subjects (P = 0.04), patients with idiopathic glomerulonephritis (P = 0.0005), and patients with lupus nephritis (P = 0.009). MPO binds to cultured human umbilical vein endothelium probably by a charge mechanism, and can react with anti-MPO antibodies in the sera of patients with microscopic polyarteritis as well as with a mouse monoclonal anti-MPO antibody. This binding of anti-MPO antibody to MPO fixed to the endothelial cell surface provides a mechanism by which endothelial injury and inflammation might occur in microscopic polyarteritis.

Endothelium, Vascular↗

Anti-idiotype and immunosuppressant treatment of murine lupus.

The effect of the administration of a xenogeneic anti-idiotype antibody (anti-Id33) to a cross-reactive idiotype (Id33) present on anti-dsDNA antibody was examined in 6-week-old (NZB/NZW) F1 (BWF1) female mice. The administration of anti-Id33 led to a transient reduction in immunoglobulins expressing Id33, followed by a rise at 30 and 34 weeks that was significantly higher than in untreated mice (P less than 0.05). Likewise, anti-dsDNA antibody levels were significantly higher at 10 and 18 weeks than in untreated mice (P less than 0.01). No differences were seen in survival to 40 weeks, proteinuria or the severity of glomerulonephritis. Concurrent administration of cyclosporin A (CyA) with anti-Id33 markedly ameliorated glomerular injury and proteinuria and improved survival. By contrast, glomerular injury, proteinuria and survival were worse in mice treated with cyclophosphamide plus anti-Id33, compared with untreated mice. Neither CyA nor cyclophosphamide treatment, when given with anti-Id33 altered serum levels of anti-dsDNA, anti-ssDNA or Id33+ immunoglobin, compared with untreated mice. The different effects of CyA and cyclophosphamide on T lymphocytes and their discrepant effects on glomerular injury when given with anti-Id33 in this model lead us to postulate a role for T lymphocytes in the glomerular injury of BWF1 lupus.

Animals↗

Urinary IL-6: a marker for mesangial proliferative glomerulonephritis?

A prospective study of plasma and urinary interleukin-6 (IL-6) levels was performed in 54 patients undergoing renal biopsy to determine whether detectable urinary IL-6 was a reliable marker for mesangial proliferation. Interleukin-6 was found in both the urine and plasma of seven patients, the urine alone of 15 patients, and the plasma alone of two patients. Interleukin-6 was not detected in the urine or the plasma of the remaining 30 patients, the urine of 10 healthy controls or the urine of 10 patients with rheumatoid arthritis with raised plasma IL-6. Interleukin-6 was found in the urine of only one out of an additional seven patients with lupus nephritis. Urinary IL-6 was associated with a variety of renal abnormalities and was not restricted to those with mesangial hypercellularity. Furthermore, many patients with mesangial hypercellularity did not have detectable urinary IL-6. There was no correlation between urinary IL-6 and plasma IL-6, urinary albumin excretion or urinary creatinine. These results suggest that IL-6 detected in the urine is a marker of renal IL-6 production, but not specifically of mesangial hypercellularity. The patients with IL-6 in the urine had a mean serum creatinine significantly higher than those without IL-6. It is not possible to distinguish at present whether IL-6 contributes to renal dysfunction or whether it reflects renal damage.

Adolescent↗

Inner ear deafness in Wegener's granulomatosis.

Autoimmune deafness represents a heterogeneous group of disorders in which there is though to be inner ear and/or middle ear damage mediated by various immunological abnormalities. We describe a patient with Wegener's granulomatosis in whom there was evidence of significant inner ear damage caused by vasculitis, which was completely reversed by cyclophosphamide and prednisolone. We propose that Wegener's granulomatosis is a cause of autoimmune deafness.

Adult↗

Assessment of glomerular size in renal biopsies including minimal change nephropathy and single kidneys.

A method of assessing glomerular size on sections of post-mortem kidney was adapted for use on needle biopsies of kidney. A semi-automatic image analyser was used to measure the cross-sectional area of the outline of Bowman's capsule on all glomeruli in renal biopsies. The mean of approximately the largest 25 per cent of areas was calculated. The method was used to compare glomeruli in 13 control patients without obvious structural abnormalities with those in 10 patients with a single kidney, 22 with minimal change nephropathy, and 20 with membranous nephropathy. Patients were at least 14 years old. Glomeruli in minimal change nephropathy were significantly smaller than those in all other groups. Glomeruli in single kidneys were significantly larger than those in all other groups. Glomeruli in membranous nephropathy were the same size as controls. Any differences between groups could not be explained by differences in body build. It is possible that in adults glomeruli in minimal change nephropathy are abnormally small. The method of assessing glomerular size can be used on renal biopsies as well as on sections of whole kidney.

Adolescent↗

Acquired cystic disease of the kidney: ultrasound as the primary screening procedure.

Patients with end-stage renal disease on long term dialysis may develop de novo renal cystic disease. We used ultrasound as a primary screening procedure for renal cysts in 71 patients. In seven patients (10%) the native kidneys could not be identified. In 35 patients renal cysts were identified indicating a prevalence of acquired renal cystic disease of 49%.

Adult↗

Anti-myeloperoxidase antibodies in systemic vasculitis.

Anti-neutrophil cytoplasmic antibodies (ANCA) are important diagnostic markers in vasculitic disorders. In a study of 164 patients with various clinical syndromes associated with vasculitis, 60 were found to have the antibody, as detected by indirect immunofluorescence; 23 had the so-called perinuclear antibody pattern, and of these, 15 had antibodies to neutrophil myeloperoxidase in an ELISA. These patients had multi-system involvement, and 14 of the 15 had histological evidence of small-vessel arteritis in the kidneys. In preliminary experiments, the isolated IgG from one patient was shown to inhibit luminol-dependent chemiluminescence of fluid phase myeloperoxidase.

Autoantibodies↗

The Medical Research Council trial of short-term high-dose alternate day prednisolone in idiopathic membranous nephropathy with nephrotic syndrome in adults. The MRC Glomerulonephritis Working Party.

We have assessed the medium-term effect of a short course of high-dose, alternate-day prednisolone on adult nephrotic patients with membranous nephropathy, using a randomized, prospective, double-blind, controlled trial. Patients were entered over the period 1981 to 1984 and were observed for a minimum of three years. One hundred and seven adult patients who had not previously received immunosuppressive treatment were included in the trial. One hundred and sixty further patients, excluded from the trial, but with membranous nephropathy were identified, followed and assessed retrospectively at the end of the trial. At 36 months there was no significant difference between control and treatment groups in plasma creatinine, creatinine clearance or 24-h excretion of protein. At between three and six months serum albumin concentrations were higher and protein excretions lower in the treatment group compared to controls. No significant benefit was therefore observed on renal function in the medium term.

Adult↗

Prognostic factors in acute renal failure following aortic aneurysm surgery.

This study analyses the prognostic factors associated with survival in 70 patients who developed acute renal failure following surgery for an aortic aneurysm. Forty-nine patients (70 per cent) had surgery for a ruptured aortic aneurysm and 21 patients (30 per cent) had an elective procedure. Fifty-nine patients received haemodialysis. Thirty-three patients (47 per cent) survived the episode of acute renal failure. Six of these thirty-three patients died within three months of recovering from acute renal failure, giving an overall survival of 27/70 (39 per cent). A stepwise logistic regression analysis showed that the following factors significantly adversely affected survival: a need for inotropic support, ventilation for more than three days and age over 65 years. A model developed using these variables provided a basis for predicting outcome.

Acute Kidney Injury↗

Different types of segmental sclerosing glomerular lesions in six experimental models of proteinuria.

From 133 to 615 glomeruli were examined in sections of kidneys from each of 60 animals, representing six rodent models of proteinuria. Particular attention was paid to the position of segmental lesions. Lewis rats given sheep anti-rat glomerular basement membrane antibodies had lesions almost exclusively at the glomerulo-tubular junction. Wistar rats on a diet of 24 per cent casein or with subtotal nephrectomy and a diet of 24 per cent soya had lesions mainly at the hilum. Wistar rats given bovine serum albumin had global lesions but virtually no segmental lesions. Wistar rats given puromycin aminonucleoside had lesions at the glomerulo-tubular junction and global mesangial abnormalities shortly after the treatment but later developed segmental lesions at all parts of the glomerulus. Untreated BUF/Mna rats had lesions at the glomerulo-tubular junction early in life but later had lesions at all parts of the glomerulus. Untreated NZB/NZW hybrid mice had various types of glomerulonephritis and also had lesions at the glomerulo-tubular junction. These findings showed that (1) segmental lesions at the glomerulo-tubular junction, or glomerular tip, occur in experimental animals, a fact not previously reported, and these tip changes are a common feature in several different models of proteinuria; (2) hilar segmental lesions are seen in conditions with hyperfiltration of protein; and (3) segmental lesions at various parts of the glomerulus are seen in some models of proteinuria and probably indicate late effects of random toxic damage to the glomerulus. Thus, there are at least three different types of segmental glomerular lesions in experimental animals--tip, hilar, and random--with different morphology and pathogenesis. It is likely that these findings can be extended to human renal diseases with segmental glomerular lesions. This will help to clarify the controversial and unsatisfactory term focal segmental glomerulosclerosis.

Animals↗

T-cell-independent and T-cell-dependent antibody responses in patients with chronic renal failure.

Antibody responses against pneumococcal capsular antigens and tetanus toxoid were measured in 14 patients with chronic renal failure who were managed by continuous ambulatory peritoneal dialysis (CAPD) or haemodialysis (HD) and in eight healthy controls. IgG antipneumococcal responses were predominantly of the IgG2 and to a lesser extent IgG1 subclasses, while the IgG response against tetanus toxoid was largely IgG1 with smaller amounts of IgG4 and IgG3. The post-immunisation serum levels of IgG1 and IgM antibody against both antigens were significantly reduced in the uraemic patients compared with controls (P less than 0.05). All the uraemic patients had normal levels of IgG, IgA and IgM in the serum, but elevated levels of IgG3 prior to immunisation. The mechanisms responsible for the asymmetric depression of antibody responses in uraemia are unclear and may account in part for the increased susceptibility to infection in these patients.

Adult↗

Vancomycin and ceftazidime in the treatment of CAPD peritonitis.

102 episodes of continuous ambulatory peritoneal dialysis (CAPD) peritonitis were studied prospectively during a 288-day period at The Queen Elizabeth Hospital, Birmingham. Organisms were isolated from 76% of the episodes, with coagulase-negative staphylococci, being the most commonly encountered organism (55%). Initial treatment consisted of intraperitoneal vancomycin and ceftazidime with subsequent adjustment on the basis of antibiotic sensitivities. With this regimen, 83% of the positive cultures became negative by 72 h, 9.8% of cases relapsed and removal of the CAPD catheter was necessary in 8 patients (7.8%). Overall, 92% of cases were cured. No adverse drug reactions were seen. This combination of antibiotics appears effective and safe in the treatment of CAPD peritonitis.

Adolescent↗

Selective conversion from azathioprine to cyclosporin for steroid-resistant rejection in renal transplants: an alternative therapy.

In 153 consecutive renal allograft recipients whose initial immunosuppression was prednisolone and azathioprine, 41 developed acute rejection episodes that were not reversed by 5-9 g of intravenous methylprednisolone. Renal histology showed cellular rejection in ten patients, vascular rejection in 12, and mixed cellular and vascular rejection in 16. Thirty-one patients were converted to cyclosporin in the first month post-transplant and ten in the second month. At the time of conversion, 20 patients were dialysis dependent and in the remainder the mean serum creatinine was 353 mumol/l (range 139-548 mumol/l). Renal function improved in 31 patients after conversion. Ten patients lost their grafts, of whom seven were on dialysis. There were no deaths and the 1-year graft survival was 75%. These data suggest that conversion from azathioprine to cyclosporin because of steroid-resistant rejection is an effective and safe strategy in patients whose initial immunosuppression is prednisolone and azathioprine.

Adolescent↗

IgG subclasses of PEG precipitable IgG in systemic lupus erythematosus sera.

Polyethylene glycol (PEG, 4%)-precipitated macromolecular IgG isolated from the sera of 20 patients with systemic lupus erythematosus (SLE) and 15 control subjects was analyzed for its IgG isotype concentration by single radial immunodiffusion. PEG precipitates from SLE sera had higher mean levels of IgG1, IgG2 and IgG3 and lower IgG4 than PEG precipitates isolated from normal sera although only the IgG2 levels were significantly different. Using an anti-complementary assay there was a significant correlation between the ability of parent sera to fix complement and the absolute levels of PEG precipitable IgG1, IgG2 and IgG3. These data suggest that the ability of immune complexes in the sera of patients with SLE to fix complement is dependent on their IgG subclass composition.

Chemical Precipitation↗