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Biomedical subjects

C M Lockwood

Publications and source records attributed to C M Lockwood.

At least 163 records · Page 9Linked to original sources
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

Goodpasture's syndrome: treatment with plasmapheresis, immunosuppression, and anticoagulation.

We report 3 children with Goodpasture's syndrome. In 2 children the diagnosis was delayed, treatment began late, and they did not recover renal function. In the third child early diagnosis and intensive treatment with plasmapheresis, immunosuppression, and anticoagulation resulted in an initial return of renal function after a prolonged period of anuria. In this child, however, although there was no evidence of disease activity, further deterioration of renal function subsequently occurred.

Anti-Glomerular Basement Membrane Disease↗
PubMed1983

Effects of cyclophosphamide on autoantibody synthesis in the Brown Norway rat.

The effects of cyclophosphamide on autoantibody synthesis were studied in an experimental model of glomerulonephritis due to autoantibodies to the glomerular basement membrane (GBM). Brown Norway rats develop anti-GBM antibodies, as part of a polyclonal response, when repeatedly injected with mercuric chloride (HgCl2). Anti-GBM antibody levels peak between days 11 and 14 and thereafter rapidly fall; convalescent animals show a time-dependent resistance to rechallenge with HgCl2 which remains significant for up to 3 months. The administration of cyclophosphamide, as a single intramuscular injection at day 0, has three distinct dose-dependent effects on anti-GBM antibody production. Firstly, lower doses (2.5 mg/kg) increase antibody levels at the time of peak response; secondly, higher doses (greater than or equal to 20 mg/kg) prevent antibody synthesis following HgCl2; and thirdly, the higher doses also reduce the response to rechallenge with HgCl2 3-4 months later. These effects of cyclophosphamide also apply to the polyclonal response to HgCl2, as judged by measurement of total IgG concentrations. Further investigation of the mechanisms of action of cyclophosphamide in this model should provide information relevant to the treatment of human autoimmune disease.

Animals↗
PubMed1983

Production of a monoclonal antibody to autoantigenic components of human glomerular basement membrane.

We describe a mouse monoclonal antibody which reacts on immunoblotting with those components of collagenase digested human glomerular basement membrane (GBM) that are also recognized by autoantibodies in sera from patients with anti-GBM nephritis. Competition between the monoclonal antibody and anti-GBM autoantibodies was demonstrated in a solid phase radioimmunoassay, suggesting that both are directed against the same autoantigen.

Animals↗
PubMed1983

Plasma exchange and immunosuppressive drugs in the treatment of glomerulonephritis due to antibodies to the glomerular basement membrane.

Glomerulonephritis due to autoantibodies to the glomerular basement membrane (GBM) usually results in the rapid development of renal failure in untreated patients. We report our experience of the use of plasma exchange and immunosuppressive drugs in the management of this condition. Treatment consisted of daily 4 litre plasma exchanges for plasma protein fraction, together with prednisolone 60 mg daily (reducing to 20 mg daily by 4 weeks), cyclophosphamide 3 mg/kg daily and azathioprine 1 mg/kg daily. It was found that plasma exchange was generally required for 2 weeks, and cytotoxic drugs for 8 weeks. Forty four patients, aged 4 to 72 years, were treated. Anti-GBM antibody production was rapidly controlled, and in 21 of 34 patients antibody was undetectable within 8 weeks. Of 22 oliguric patients, none recovered renal function, 16 remained dialysis-dependent and 6 died; of 5 patients whose initial plasma creatinine was greater than 600 mumol/l, one improved and 4 proceeded to dialysis; and of 17 patients whose creatinine was less than 600 mumol/l, 15 recovered renal function, one became dialysis-dependent and one died. Long term follow-up of those who improved revealed that 2/16 subsequently deteriorated. Our results represent a great improvement in the prognosis of anti-GBM disease, and demonstrate that the majority of patients will recover renal function if treated before irreversible glomerular damage has occurred.

Adolescent↗
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↗
PubMed1981

Studies on NEM-treated erythrocyte clearance in the rabbit, with special reference to the effects of circulating immune complexes.

The splenic component of mononuclear phagocytic cell function was investigated in rabbits using as a marker the clearance of N-ethylmaleimide-treated, technetium-labelled autologous erythrocytes. In 66 clearances performed in 23 normal rabbits, the clearance T1/2 was found to be between 5 and 16 min, the value for each rabbit remaining relatively constant. Clearance was proportional to incubation time or the dose of N-ethylmaleimide used. Clearance was delayed following injection of 20 to 65 mg of preformed complexes of BSA-anti-BSA made in 10-fold antigen excess. The degree and duration of this blockade was related to the dose of the complexes up to a critical value of 20 mg (antibody content after which no further decrease in clearance occurred although the duration of the blockade was longer at higher doses. Ultracentrifugation studies showed that these complexes were about 14S in size and sequential studies revealed that they were slowly cleared from the circulation. The experiments indicate that studies of splenic function may be of value in assessing immune complex disease, since circulating immune complexes of these characteristics are poorly detected by current methodology.

Animals↗
PubMed1980

Amyloid P-component is a constituent of normal human glomerular basement membrane.

Glomerular and other vascular basement membranes were found to contain an antigen that was immunochemically indistinguishable from serum amyloid P-component. There was no immunological cross-reactivity between antisera to serum amyloid P-component and to collagen types I, III, IV, or V. The amyloid P-component antigen was confined to the endothelial aspect, the lamina rara interna, of glomerular basement membrane. It could not be eluted by high-ionic-strength saline, EDTA, dithiothreitol, or either polar or nonpolar detergents, but was released into solution when isolated glomerular basement membrane was digested by highly purified bacterial collagenase. Most of these P-component molecules and their constituent polypeptide chains were of higher molecular weight and lower isoelectric point than serum amyloid P-component. These findings indicate that, as well as being a normal plasma protein and a universal constituent of amyloid deposits, P-component is also a normal matrix glycoprotein of basement membrane in which it is covalently linked to collagen and/or other matrix proteins. This may be relevant both to the pathogenesis of amyloidosis and to other aspects of physiology and pathology of basement membranes.

Amyloid↗
PubMed1980

Relapses in Wegener's granulomatosis: the role of infection.

Out of 20 relapses that occurred in patients with Wegener's granulomatosis, nine were provoked by bacterial or viral infection. Seven of these occurred during maintenance treatment in response to infection with common pathogens, and treatment of the infection alone was insufficient to produce remission. Circulating immune complexes were seen only in relapses due to infection and rarely in infections that occurred without relapse. A possible mechanism for infection-provoked relapses is that infection-derived complexes reactivate disease; alternatively, the acute-phase or cellular response to infection may enhance quiescent disease. Infection may exacerbate Wegener's granulomatosis and other autoallergic diseases, but whether it does so by a common mechanism is not known and further study is required.

Antigen-Antibody Complex↗
PubMed1980

Amyloid P-component in human glomerular basement membrane. Abnormal patterns of immunofluorescent staining in glomerular disease.

Serum amyloid P-component (SAP) is a normal plasma protein and is a constituent of normal human glomerular basement membrane. Immunofluorescence with anti-SAP antibody produced characteristic linear staining along the glomerular basement membrane in normal kidney. Distinctive abnormal staining patterns were seen in renal biopsy specimens from patients with diabetes, membranous glomerulonephritis, mesangiocapillary nephritis, systemic vasculitis, Goodpasture's syndrome.

Amyloid↗
PubMed1979

Inhibition of reticuloendothelial function by gold and its relation to postinjection reactions.

A patient with rheumatoid arthritis developed severe exacerbation of symptoms 18 hours after an injection of gold thiomalate (sodium aurothiomalate). Immune complexes were present in his serum and synovial fluid; in the synovial fluid they were associated with intense complement activation. The effect of gold salts on splenic reticuloendothelial function was determined by measuring the clearance of heat-damaged erythrocytes from the circulation. Gold thiomalate (50 mg) substantially delayed clearance in the patient but had no effect in four other patients with rheumatoid arthritis who had not had a postinjection reaction. Severely impaired clearance also occurred in three out of four healthy people given 100 mg gold but they remained asymptomatic. The postinjection reaction may be an immune-complex disease that is triggered in certain patients because gold transiently inhibits reticuloendothelial function.

Arthritis, Rheumatoid↗
PubMed1979

Defective reticuloendothelial system function in rheumatoid arthritis.

The function of the splenic reticuloendothelial system in patients with rheumatoid arthritis (R.A.) was assessed by determining the clearance of autologous heat-damaged erythrocytes from the circulation. 11/13 patients with active R.A. had a defect in the clearance of red cells and there was a significant inverse correlation between splenic function and the level of circulating immune complexes detected by a Clq-binding assay. Splenic function was normal in 13 patients with inactive disease who had been treated with either gold or prednisone. A serial study on 1 patient with active R.A. showed a clear correlation between fluctuations in disease activity, splenic function, and the level of circulating immune complexes.

Adult↗
PubMed1979

Reversal of impaired splenic function in patients with nephritis or vasculitis (or both) by plasma exchange.

By studying the clearance of autologous labeled antibody-coated or heat-damaged erythrocytes, we showed that reversible blockade of the splenic component of reticuloendothelial function existed in 14 of 15 patients referred for treatment of nephritis or vasculitis. In 10 patients treated by plasma exchange--alone in three and combined with steroids and cytotoxic drugs in six--reversal of splenic blockade followed in nine, and in the three patients treated solely by plasma exchange this reversal was demonstrated to occur within 48 hours of the procedure. Only gradual reversal of splenic blockade was found in three of five patients treated by steroids with or without cytotoxic drugs; no change in splenic function was observed in two. When circulating immune complexes were detected by a C1q-binding assay, there was, in serial studies, an approximate inverse correlation between splenic function and the level of C1q-binding material, though hyposplenism was also a feature of patients in whom the C1q-binding assay was negative.

Antigen-Antibody Complex↗