Biomedical subjects
C M Lockwood
Publications and source records attributed to C M Lockwood.
Plasma exchange in nephritis.
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Value of immune-complex assays in diagnosis and management.
Two complement-dependent assays for circulating immune complexes, the C1q-binding assay and the conglutinin binding, were used to study patients with suspected immune-complex disease. Complexes were detected most frequently in multisystem disease such as infective endocarditis (69%) and systemic lupus erythematosus (60%), and less frequently in isolated nephritis (26% of membrano-proliferative nephritis). Sequential estimations in 32 patients showed that concentrations of circulating immune complexes correlated with disease activity and were useful in monitoring therapy.
Renal histology and immunopathology in distal renal tubular acidosis.
Renal biospy studies are reported from 10 patients with distal renal tubular acidosis (DRTA). On the biopsies from 6 patients who had associated immunological abnormalities immunofluorescent studies for immunoglobulins, complement, and fibrin were performed. Interstitial cellular infiltration and fibrosis were common findings in patients with and without immunological abnormalities, and were usually associated with nephrocalcinosis and/or recurrent urinary infection. No immune deposits were demonstrated in association with the renal tubules. This study shows that DRTA in immunologically abnormal patients is not caused by tubular deposition of antibody or immune complexes. The possibility of cell mediated immune damage is discussed.
Enhanced allergic tissue injury in Goodpasture's syndrome by intercurrent bacterial infection.
Studies of 16 relapses in seven patients receiving treatment for Goodpasture's syndrome showed that intercurrent bacterial infection seemed to be the precipitating event in 13 cases, whereas a rising antibody titre to glomerular basement membrane was responsible in only one. This association between infection and relapse in Goodpasture's syndrome has several implications for the pathogenesis of antibody-mediated tissue damage, and, clearly, more experiments are needed. Whatever the explanation, however, prevention and early diagnosis and treatment of infection in anti-GBM disease are important.
Plasma-exchange and immunosuppression in the treatment of fulminating immune-complex crescentic nephritis.
Nine patients with fulminating immune-complex crescentic nephritis were treated by a regimen of intensive plasma-exchange, steroids, and cytotoxic drugs. In five patients with severe renal failure there was early and rapid improvement in renal function; in one patient an early but extensive focal necrotising glomerulitis was arrested; in two patients improvement was delayed for 3 and 7 weeks and could not confidently be attributed to therapy; one patient, anuric at presentation, did not recover renal function. Follow-up renal biopsy specimens, obtained in three patients, showed no evidence of active disease. With the Clq-deviation test, circulating immune complexes were detected in five patients before treatment and had disappeared when renal function had improved and stabilised: these patients showed the best response to therapy. In three patients temporary withdrawal of plasma-exchange was followed by the reappearance of immune complexes in the circulation and was accompanied in two patients by deterioration in renal function; reintroduction of plasma-exchange was followed by elimination of immune complexes and further improvement in renal function.
Plasma exchange in glomerular and related auto-allergic diseases.
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Immunosuppression and plasma-exchange in the treatment of Goodpasture's syndrome.
Seven patients with Goodpasture's syndrome induced by anti-glomerular-basement-membrane (anti-G.B.M.) antibody were treated by a regimen of intensive plasma-exchange, cytotoxic drugs, and steroids. In the three patients retaining some renal function at presentation, this regimen led to suppression and eventual termination of antibody synthesis with improvement in renal function. In four patients, all anuric at presentation, antibody to G.B.M. persisted with variable reduction in the circulating levels. No return of renal function occurred in this group, all of whom had extensive changes on renal biopsy. Pulmonary haemorrhage, life-threatening in one patient, was rapidly controlled in all five patients in whom it was a presenting feature. In addition to its effect on antibody levels, plasma-exchange, using volume-replacement with plasma-protein fraction (P.P.F.), resulted in substantial depletion of complement and fibrinogen, mediators possibly contributing to the antibody-induced injury.
Recovery from Goodpasture's syndrome after immunosuppressive treatment and plasmapheresis.
A patient with Goodpasture's syndrome has recovered after treatment with immunosuppressive drugs (cyclophosphamide and prednisolone) and removal of circulating antibodies by plasma exchange. This was performed on seven occasions and seems to have hastened the decline in circulating antibody levels. Undertaken early in the course of the disease plasmapheresis could prove a useful addition to its therapy.
A case of duodenal tuberculosis.
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Intracellular potassium in diffuse proctocolitis.
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The intracellular potassium concentration of colonic epithelial cells in health and diffuse ulcerative colitis.
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Effects of phenethyl alcohol on influenza virus growth and macromolecular synthesis in chick embryo cells.
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Spectrum of autoimmune responses in systemic vasculitis.
Growing evidence supports the inclusion of primary forms of systemic vasculitis within the category of autoimmune diseases. Thus their association with a family of autoantibodies, related to their specificity or neutrophil cytoplasm antigens, has been identified and the role these autoantibodies play in pathogenesis is now being explored. Different members of the autoantibody family have now been characterised in terms of their molecular specificity and the isotype of immunoglobulin of which they are composed. These properties may be a useful adjunct in the classification of systemic vasculitis (see table I). It is the purpose of this review to put a perspective on the specificity and pathogenicity of autoantibodies found in patients with systemic vasculitis and to outline new strategies for the treatment of these conditions, based on the involvement of autoimmune mechanisms in the development of these disorders.
Electrolyte losses in diffuse proctocolitis.
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Specificity and pathogenicity of antineutrophil cytoplasm antibodies.
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Refractory Wegener's granulomatosis: a model for shorter immunotherapy of autoimmune diseases.
BACKGROUND: Humanised monoclonal antibodies are immunomodulatory tools with high specificity and sustained therapeutic potential. We investigated the effectiveness of treatment with monoclonal antibodies to lymphocyte CD52 and CD4 in patients with Wegener's granulomatosis that had proved intractable despite conventional treatment. We also investigated whether repeated courses of monoclonal antibody treatment alone could be used to control relapses in patients in remission. METHOD: We studied 17 consecutive patients with refractory Wegener's granulomatosis seen between June 1992 and June 1996. In all patients, treatment with prednisolone and cyclophosphamide or azathioprine for at least six months had been unsuccessful, and all were followed up for at least six months after monoclonal antibody treatment. Diagnosis was established on clinical, serological and histological criteria. Disease activity in the upper airways, lungs or kidneys at referral was documented by whole-body scintiscanning, computed tomography, or isotope measurement of the glomerular filtration rate, as well as by tissue biopsy, where appropriate. Monoclonal antibodies to CD52 followed by CD4 were given intravenously in courses lasting five days each. RESULTS: Remission (programmed withdrawal of drug treatment with no return of refractory disease) was obtained in 16 patients after one course of CD52 +/- CD4, and confirmed by serial studies of abnormalities found before treatment. In one patient, disease remained unchecked. In responders, cytotoxic drugs were stopped during monoclonal antibody treatment and were not used again, while steroids were tapered off gradually. Disease relapses occurred in nine. Monoclonal antibodies alone controlled these during follow-up that totalled 30 patient years. Neither systemic opportunistic infection nor lymphoma development complicated this regimen. CONCLUSION: Monoclonal antibody treatment may be better and safer for diseases, such as Wegener's granulomatosis, that require long-term cytotoxic and steroid treatment because it speeds remission and avoids the iatrogenic complications of cumulative drug toxicity.