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Biomedical subjects

A J Rees

Publications and source records attributed to A J Rees.

At least 109 records · Page 6Linked to original sources
PubMed1985

Progression to renal failure after nephrotoxic nephritis in rats studied by renal transplantation.

We studied the relation between immunopathology and progressive renal failure after nephrotoxic nephritis (NTN) in rats. Thirty days after induction of nephritis by injection of rabbit anti-rat nephrotoxic serum, pairs of kidneys from 13 nephritic rats were transplanted into separate syngeneic recipients, one of whom had been pre-immunized with rabbit immunoglobulin G (IgG) whilst the other was naive. Progression to renal failure of the transplanted nephritic kidney was studied after removal of the recipient's own kidneys; results from right and left kidney from a single donor in pre-immunized and naive recipients were compared. There were substantial differences in autologous anti-rabbit IgG titres in naive and preimmunized recipients; despite this pairs of kidneys from the same donor had almost identical courses as assessed by proteinuria, serum creatinine and graft survival. There was substantial variation in survival of kidneys from different donors. But there were very strong correlations of graft survival with proteinuria (r = 0.97, t = 4.443, P less than 0.001) and reciprocal serum creatinine (r = 0.95, t = 4.32, P less than 0.001) in donors shortly before transplantation. We conclude that autologous antibody titres did not influence the progression to renal failure after nephrotoxic nephritis. The rate of progression was already determined at the time of transplantation.

Animals↗
PubMed1985

Evidence against a role for superoxide ions in the injury of nephrotoxic nephritis in rats.

The accelerated model of nephrotoxic serum nephritis (NTSN) was produced in 12 Sprague-Dawley rats. Six of these rats were administered superoxide dismutase (EC 1.15.1.1; SOD) subcutaneously (8 mg/kg) 8-hourly for 4 days. The first dose was given 6 h before the nephrotoxic serum (NTS). The progression of renal disease was monitored by following (i) albumin excretion, (ii) serum creatinine and creatinine clearance and (iii) renal histopathology and immunofluorescence. There was no evidence that SOD influences the course of NTSN. SOD was scarcely excreted by control rats or rats with NTSN.

Albuminuria↗
PubMed1985

Pneumocystis carinii pneumonia in renal transplant recipients--clinical and radiographic features, diagnosis and complications of treatment.

Six episodes of Pneumocystis carinii pneumonia in five renal transplant patients on low dose maintenance prednisolone are described. The infection was rare, occurring in 3 per cent of the recipients transplanted between 1978 and 1984. Diagnosis and treatment were not straightforward. Fever was the earliest evidence of illness, and in three episodes the chest radiograph was normal at presentation. At diagnosis, two to 16 days later, all had pulmonary infiltrates and severe hypoxia. Diagnosis was confirmed by cytological examination of bronchial lavage (two), transbronchial biopsy (one), open lung biopsy (one), and for two episodes clinically, from the rapid and complete resolution of fever, pulmonary infiltrates and hypoxia following a therapeutic trial of high dose cotrimoxazole. Pneumocystis antibody titres were low during the illness and in convalescence and did not contribute to diagnosis. Three patients had serological evidence of recent cytomegalovirus infection. All episodes responded to treatment with high dose cotrimoxazole. All the patients survived the illness but one died a year after recovery. The major complications of treatment were thrombocytopenia (three cases) and neutropenia (two cases) which did not respond to folinic acid.

Drug Combinations↗
PubMed1985

Microscopic polyarteritis: presentation, pathology and prognosis.

We have described 34 patients with microscopic polyarteritis, all of whom had clinical evidence of a systemic small vessel vasculitis predominantly affecting the skin and musculoskeletal systems accompanied by a focal necrotising glomerulonephritis with renal impairment. Thirty three patients received immunosuppressive treatment, comprising prednisolone, azathioprine, cyclophosphamide and plasma exchange in various combinations. The five-year actuarial patient and kidney survival rates were 65 and 55 per cent respectively, suggesting that aggressive immunosuppressive therapy in these patients is beneficial.

Adolescent↗
PubMed1984

Association of immunoglobulin Gm allotypes with antiglomerular basement membrane antibodies and their titer.

We studied the immunoglobulin Gm allotypes in 41 patients with glomerular nephritis caused by autoantibodies to glomerular basement membrane (GBM). Gm phenotypes of all 41 patients were attributable to combinations of the 3 Gm haplotypes commonly found in Caucasoid populations; identified by the allotypes Gm 1,21 (ag), Gm 1,2,21 (axg), and Gm 3,5,11 (fb). The incidence of the putative haplotype Gm 1,2,21 (axg) was greatly increased in the patients being present in 22 of 41 (56%) of patients compared to 28 of 167 controls. (Pcor = 1.5 X 10(-5]. The increase in Gm 1,2,21 (axg) was attributable entirely to presumed heterozygotes with the phenotype Gm 1,2,21;3,5,11 (axg;fb), with concomitant decreases in the frequencies of patients with the phenotypes Gm 1,21 (ax) and with Gm 3,5,11 (fb). Heterozygotes at Gm loci had higher titers of anti-GBM antibodies irrespective of the presence of Gm 1,2,21 (axg). Thus genes within or closely linked to the Gm complex in addition to HLA linked genes influence susceptibility to or clinical expression of anti-GBM disease.

Autoantibodies↗
PubMed1984

The influence of HLA-linked genes on the severity of anti-GBM antibody-mediated nephritis.

Thirty-nine Caucasian patients with glomerulonephritis caused by autoantibodies to glomerular basement membrane (GBM) were studied. They were segregated into three groups depending on presentation: Group 1 (19 patients) were anuric or oliguric, group 2 (13 patients) had rapidly deteriorating renal function but were not oliguric, and group 3 (seven patients) had stable renal function. The incidence of HLA-DR2 was greatly increased; it was present in 34 of 38 patients in whom DR antigens were identified compared to 43 of 154 controls (Pc = 0.63 X 10(-8), relative risk 36, etiological fraction 0.86). The incidence of HLA-B7 was also increased; present in 23 of 39 patients and 43 of 193 controls (Pc = 0.26 X 10(-4), relative risk 5.0, etiological fraction 0.43). These data were analyzed for a third order association between HLA-DR2, HLA-B7, and anti-GBM disease. Such an association was probable for patients in group 1 (P = 0.27 X 10(-6), likely for those in group 2 (P = 0.024) but unlikely for patients in group 3 (P = 0.62) suggesting HLA-B7-associated genes influence severity. Clinical results from a subset of the patients referred directly on presentation showed that patients who inherited HLA-B7 together with DR2 had significantly higher plasma creatinines, a greater proportion of glomeruli surrounded by crescents and a worse prognosis. Despite this there was little difference in severity of their lung disease.

Adolescent↗
PubMed1984

Objective monitoring of activity in Wegener's granulomatosis by measurement of serum C-reactive protein concentration.

Serial measurements of the serum concentration of C-reactive protein were made in 38 patients with Wegener's granulomatosis during a period of 6 years. The concentration was always elevated when the disease was active, even in patients receiving immunosuppressive treatment, and fell rapidly in association with clinical remission induced by immunosuppression. During periods of complete remission, in the absence of any intercurrent condition, the value remained within the normal range. The correlation between C-reactive protein level and disease activity was much closer than that between erythrocyte sedimentation rate and disease activity. These results indicate that serial measurement of the serum C-reactive protein fills the urgent need for an objective index of the activity of Wegener's granulomatosis and its response to therapy.

Adolescent↗
PubMed1983

Cigarette smoking and lung haemorrhage in glomerulonephritis caused by autoantibodies to glomerular basement membrane.

The smoking habits of 51 patients with glomerulonephritis caused by autoantibodies to the glomerular basement membrane (GBM) were investigated. 43 patients also had pulmonary haemorrhage; 8 did not. A full smoking history was obtained from 47 patients. Of these, all 37 cigarette smokers suffered lung haemorrhage, compared with only 2 of 10 non-smokers. There was no significant difference between the titres of circulating anti-GBM antibodies in smokers and non-smokers. In 1 patient resumption of smoking was closely followed by recrudescence of lung haemorrhage. These results largely explain the variable presence of pulmonary haemorrhage in anti-GBM disease.

Adolescent↗
PubMed1983

Prognosis after immunosuppression of patients with crescentic nephritis requiring dialysis.

48 patients with rapidly progressive glomerulonephritis were treated by a regimen of intensive plasma exchange, steroids, and cytotoxic drugs. All required dialysis before immunosuppressive treatment was started, and all had 50% or more of their glomeruli affected by crescent formation. Renal function was not recovered in any of the 21 patients with anti-glomerular basement membrane antibody disease. In contrast 63% of patients without these autoantibodies recovered renal function. Plasma creatinine remained stable over prolonged follow-up (6-60 months) in all but 1 of the 10 late survivors. There was no correlation between the extent of crescent formation and recovery of renal function in those patients without circulating anti-glomerular basement membrane antibodies.

Adolescent↗
PubMed1983

Effect of dietary protein restriction on the development of renal failure after subtotal nephrectomy in rats.

We have examined the effect of a low protein diet on the development of glomerular sclerosis and progressive renal failure after subtotal nephrectomies in rats. Two groups of male Sprague-Dawley rats were studied after five-sixths nephrectomy; group 1 were maintained on a normal diet (13.5 g day-1 kg-1 body weight) and group 2 were fed with a low protein diet (6 g day-1 kg-1 body weight). Rats maintained on a low protein diet survived for longer, and had significantly less glomerular sclerosis and significantly greater glomerular filtration rates when the experiment ended after 7 months. We conclude that dietary protein influences favourably the development of glomerular scarring and renal failure after subtotal nephrectomy in rats.

Animals↗
PubMed1983

Gastrointestinal manifestations of systemic vasculitis.

Systemic vasculitis is known to affect the gastrointestinal tract but the nature of the complication is poorly characterized. Out of 65 patients with systemic vasculitis, the majority of whom had renal disease, the intestine was found to be affected in 18. These comprised four of eight patients with polyarteritis nodosa, nine of seventeen with microscopic polyarteritis, four of thirty-six with Wegener's granulomatosis and one of four with Churg-Strauss syndrome. The features included abdominal pain (85 per cent), diarrhoea (50 per cent), gut haemorrhage (44 per cent) and abnormal liver function tests (50 per cent). Manifestations of gastrointestinal disease were evident at presentation in half the patients and led to a fetal outcome in five. Ileus, mucosal abnormalities, perforation and slow transit were evident radiographically, and selective visceral angiography showed aneurysms or organ infarcts in five patients. Histological assessment of gut biopsies (chiefly rectal) revealed non-specific inflammation or ulceration in nine patients and intramucosal haemorrhage in two. Focal areas of necrosis and ulceration in colonoscopic biopsies were highly suggestive of vasculitis whereas arteritis was only found in one full thickness biopsy. Hence the diagnosis of gastrointestinal complications depends largely on clinical evidence. In patients who survived, the gastrointestinal features remitted as the systemic illness improved following treatment with steroids, cyclophosphamide or plasma exchange.

Abdomen↗
PubMed1983

Factors affecting severity of injury during nephrotoxic nephritis in rabbits.

All 22 rabbits injected with sheep globulin containing high titres of antibodies to rabbit glomerular basement membrane (GBM)--nephrotoxic globulin (NTG)--developed antibodies to sheep IgG. Despite this only 15 rabbits developed obvious autologous phase injury. Eleven days after injection of NTG titres of autologous antibody to sheep IgG were similar in rabbits with and without definite autologous phase injury but were detected earlier and rose significantly more rapidly in those with autologous phase injury. In experiments on heterologous phase injury after intravenous injection of NTG, binding of defined amounts of nephrotoxic antibodies (NTAb) to the GBM after bolus injection caused significantly more injury, assessed by proteinuria, than binding of similar amounts of NTAb after infusion of NTG over 3 h (P less than 0.02 Student's paired t-test). In in vitro experiments, aliquots of homogenized rabbit kidney taken 2 days after injection of NTG bound appreciable amounts of rabbit anti-sheep Ig whereas homogenates of kidneys taken 20 days after NTG showed no such binding. These results show that the rate of deposition of NTAb in kidney influences the severity of injury in heterologous and autologous phases of NTN and that antigenic sites or heterologous IgG fixed to the GBM become saturated during the autologous phase of injury.

Animals↗
PubMed1983

Acute and chronic nephritides: two different diseases?

The role of the immune system in the progression of experimental nephrotoxic serum nephritis (NTN) in rats has been evaluated. Proteinuria and renal functional impairment during the sub-acute phase of the disease determined the long-term prognosis of the nephritis regardless of the humoral autologous antibody levels. In contrast to the acute, immune mediated glomerulonephritis, chronic glomerular scarring in NTN proceeds independently of the host immune response.

Acute Disease↗
PubMed1983

Wegener's granulomatosis: observations on 18 patients with severe renal disease.

Eighteen patients with Wegener's granulomatosis with renal involvement have been studied. Their course before treatment has indicated how the disease may progress and has provided a framework for diagnosis based on clinical and radiological features combined with available histology. The need for such diagnostic criteria is emphasised by the fact that a firm histopathological diagnosis could only be made in nine patients. A strong association between Wegener's granulomatosis and previous suppurative or tuberculous respiratory infection has been noted as well as between intercurrent infection and relapse. Evidence that immune complexes play a pathogenetic role has come from the association between active disease and circulating immune complexes. The observation of a reversible abnormality of splenic clearance of altered red cells suggests that immune complex handling by the spleen is defective. Treatment of these patients has shown a surprising degree of reversibility in many manifestations, especially renal failure. Remissions occurring spontaneously or induced by steroids alone are temporary and steroids, if used alone, may adversely affect outcome. While confirming the central role of cyclophosphamide in the induction of remission, this study has indicated that its combination with steroids and/or plasma exchange may be valuable in initial control of fulminating disease. The fact that seven patients died during induction (as well as a further four in the succeeding five years) reflects the advanced disease at presentation and the infective problems associated with immunosuppressive therapy. This highlights the need for earlier diagnosis.

Adrenal Cortex Hormones↗
PubMed1982

Enumeration of lymphocyte populations in whole peripheral blood of patients with antibody-mediated nephritis during treatment with cyclosporin A.

Lymphocyte populations identified by surface markers were enumerated in whole peripheral blood of 3 patients with Goodpasture's syndrome (mediated by anti-glomerular basement membrane antibody) whilst on treatment with cyclosporin A (CSA). The whole blood method, using alkaline phosphatase-labelled reagents, permits precise enumeration of the relative and absolute numbers of lymphocyte subsets in the circulation. Using conventional rabbit and monoclonal mouse anti-human T-cell antibodies, a small decrease in the percentage of T-lymphocytes was noted following the start of CSA treatment. The absolute T-cell count fell, but only to just below normal. There was no marked or consistent effect on the percentages or absolute numbers of B-cells, C3b-receptor or Fc(gamma)-receptor bearing lymphocytes. These results are compatible with a mechanism of immunosuppression by CSA in which there is selective inhibition of a relatively minor subset of T-lymphocytes.

Adolescent↗
PubMed1982

Perioperative changes in complement associated with cardiopulmonary bypass.

The total haemolytic complement (CH50), the complement components C3 and C4, the complement breakdown product C3d, alternative pathway activation and transferrin, were measured before, during and after cardiopulmonary bypass. As expected, CH50 decreased after heparinization, remained low during bypass and decreased further up to 8 h after bypass. C3 and C4 decreased significantly during bypass, continued to decrease for a further 8 h after bypass (by 35% and 40% respectively) and thereafter increased gradually up to 48 h. Although the depletions observed were suggestive of complement activation, there were no demonstrable increases in C3d, and in all patients the concentration of C3d remained within the normal range. Hence it was concluded that complement depletions of this magnitude were unlikely to result from complement activation. Non-specific changes in protein concentrations during bypass, as a result of dilution, redistribution or other unidentified factors, are more probable causes of the observed reductions. The acute phase response to surgery may be a factor in the subsequent increase in C3 and C4 which is seen 24 h after bypass. As transferrin concentrations in the plasma are known to decrease during this response the observed decrease in transferrin concentration would support this view.

Adult↗
PubMed1982

Complement in CPD-stored blood.

We studied complement functions, breakdown of C3 and aggregation of immunoglobulins in whole blood stored in citrate phosphate dextrose at 4 degrees C for up to 3 weeks from 10 normal blood donors. No significant changes in total haemolytic complement (CH50) and alternative pathway haemolytic complement activity were detected. However, the complement-mediated capacity of the sera to solubilise a pre-formed immune precipitate decreased significantly at 2 and 3 weeks (p less than 0.02 at 2 weeks, p less than 0.003 at 3 weeks). No C3 conversion could be detected by immunoelectrophoresis but alteration in C3 was attested by a significant increase in breakdown products of C3 by 1 week (p less than 0.002) and all were above the normal range after 3 weeks (p less than 0.0001). No aggregation of immunoglobulins could be detected using two immune complex assays.

Antigen-Antibody Complex↗