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Biomedical subjects

A R Clarkson

Publications and source records attributed to A R Clarkson.

At least 19 recordsLinked to original sources

Serum immune complexes and disease.

The solid phase Clq radioimmunoassay was used to detect immune complexes in sera from patients with systemic lupus erythematosus (14/25), rheumatoid arthritis (4/5), vasculitis (5/15), infective endocarditis (2/2), acute rheumatic fever (2/3), pre-eclamptic toxaemia (0/14), lung cancer (3/7), glomerulonephritis (26/98) and renal transplant patients (0/5). The best correlation with disease activity was seen in systemic lupus erythematosus and infective endocarditis where serial immune complex determinations were clearly of value in monitoring therapy. The findings in primary glomerulonephritis indicate only a limited usefulness of the assay in that serum immune complexes were detected in a minority (22/73) of patients with glomerular immune deposits. In particular the data do not support a role for Clq fixing immune complexes in the pathogenesis of membranous glomerulonephritis or in pre-eclamptic toxaemia.

Antigen-Antibody Complex

Plasmapheresis in glomerulonephritis.

Plasmapheresis together with immunosuppressive drug therapy has been used in the treatment of 17 patients with glomerulonephritis [Goodpasture's syndrome (4), systemic lupus erythematosus (4), mesangiocapillary glomerulonephritis (2), glomerulonephritis associated with cirrhosis (2), nonspecific mesangial proliferative glomerulonephritis (3), Henoch-Schoenlein purpura glomerulonephritis (1) and glomerulonephritis associated with infective endocarditis (1)]. Use of the Haemonetics Model 30 blood cell separator, exchanging two liters of plasma with 5% albumin in Hartmann's solution has provided a safe, effective but relatively expensive procedure, capable of producing a marked reduction of fibrinogen, complement components, anti-glomerular basement membrane antibody and immune complex concentrations. Removal of one or more of these factors is felt to be at least partly responsible for the improvement in renal function and clinical well-being demonstrated in patients with Goodpasture's syndrome, systemic lupus erythematosus and other forms of glomerulonephritis associated with the presence of circulating immune complexes.

Adolescent

Concomitant IgA nephropathy and cyclical neutropaenia.

A case of concomitant cyclical neutropaenia and IgA nephropathy, a previously undescribed combination is reported. The patient has recurrent aphthous ulceration, and haematuria occurs with these episodes. The diagnosis of cyclical neutropaenia was based on the clinical features and serial peripheral blood studies, and a renal biopsy studied by light, electron and immunofluorescence microscopy in conjunction with the clinical features established the diagnosis of IgA nephropathy. Elevation of serum immunoglobulin, with a disproportionate elevation of IgA was found. The features of this case emphasise the importance of infection as an initiating event in the pathogenesis of IgA nephropathy, and they provide further evidence for the formation of poorly soluble immune complexes as a likely pathogenetic mechanism.

Agranulocytosis

Metformin associated lactic acidosis.

A case of lactic acidosis occurring in association with inappropriate and excessive metformin therapy and a high serum metformin concentration is described. In the other 23 cases of metformin associated lactic acidosis reported to December 1977, renal, cardiovascular and liver disease were common. Although metformin is less likely to cause lactic acidosis than phenformin, neither drug should be prescribed in the presence of renal, hepatic or cardiovascular disease.

Acidosis

Phenistix in screening.

Screening procedures have achieved notoriety in recent years because of their ability to detect diseases in their early phases and also because of their expense. This paper describes a little-known but simple urine screening test which, if used judiciously, may help with diagnosis and treatment, and yet remain relatively inexpensive.

Analgesics

Paraquat poisoning is not necessarily fatal.

This paper describes a case of deliberate ingestion of paraquat successfully managed with gastric lavage, forced diuresis, haemodialysis, gastrointestinal purgation and the adminstration of specific adsorbents.

Adult

Persistent acute renal failure with renal artery stenosis: cure following reconstructive arterial operation.

A case of acute renal failure is reported in which renal function returned after surgical correction of renal artery stenosis to the sole functioning kidney. Acute renal failure associated with renal vascular lesions is reviewed. Although often clinically apparent vascular obstruction may be asymptomatic and should be considered in cases of prolonged acute renal failure.

Acute Kidney Injury

Salivary antipyrine kinetics in hepatic and renal disease and in patients on anticonvulsant therapy.

The effects in man of liver disease, renal failure and hepatic microsomal enzyme induction on the elimination kinetics of antipyrine in saliva have been examined. Antipyrine (10 mg/kg) was given orally and assayed in saliva by gas-liquid chromatography. The mean antipyrine half-life from saliva in nine epileptic subjects receiving long term anticonvulsant drug therapy (6 hr +/- 0-9 SEM) was significantly shorter than in twenty normal healthy volunteers (10-7 +/- 0-6). Therapy included phenytoin and phenobarbitone, two drugs known to induce hepatic microsomal enzymes. Five subjects with chronic renal failure exhibited no significant difference in salivary anti-pyrine half-life (11-7 +/- 1-9) compared to the control group, whereas six subjects with chronic liver disease and impaired hepatic function had significantly increased half-life values (42-4 +/- 10). The results suggest that differences in the activity of hepatic microsomal enzymes are reflected by changes in salivary antipyrine elimination kinetics. Chronic renal failure appeared to have no effect on the function of these enzymes.

Adult

IgA nephropathy: a syndrome of uniform morphology, diverse clinical features and uncertain prognosis.

Isolated glomerulonephritis with mesangial IgA deposits was the most common single finding encountered in a large biopsy series in an Australian community and was found in 50 patients, 18% of those presenting for the investigation of primary glomerular disease. A uniform histopathological picture of mesangial enlargement, with or without focal and segmental features was present. A tendency to progression was suggested by the frequent presence of glomerulosclerosis, interstitial scarring and vascular hyalinization. Because of the uniform histological immunofluorescence and ultrastructural appearances, the term IgA nephropathy has been used for this condition. The clinical picture, however, was heterogenous. Presenting symptoms included macroscopic hematuria (34%), proteinuria (32%) acute nephritis (10%), nephrotic syndrome (6%), malignant hypertension (8%), acute renal failure (6%) and chronic renal failure (4%). There was a striking correlation of increased blood pressure and decreased renal function with increasing age. While the period of follow-up was too short to assess individual patient data, a gradual and progressive decrease in renal function over several decades is suspected in patients with this condition.

Adolescent

Renal and cardiac complications of drug abuse.

The case is presented of a young man who, after prolonged intravenous narcotic administration, developed subacute bacterial endocarditis involving the aortic valve, and rapidly progressive glomerulonephritis. After treatment of and recovery from renal failure, persistent proteinuria was shown to be caused by focal glomerulosclerosis. The association of these lesions with "mainlining" is reviewed.

Adult

Coagulation and renal disease.

The role of coagulation in relation to the aetiology, pathogenesis and progression of renal diseases is discussed. The intimate interdependence between the coagulation process and platelet function, fibrinolysis, complement activation and kinin release is emphasized; these processes are usually involved in most types of immunological inflammation. Coagulation abnormalities occurring in distinct renal diseases are reviewed and the benefits derived from therapy aimed at correcting these abnormalities are compared with the known natural histories of these diseases.

Animals

Phenformin and lactic acidosis.

Thirty-eight patients who presented with diabetes and a changed state of consciousness satisfied the criteria for lactic acidosis. Sixteen patients were non-ketotic, and 15 of these were receiving phenformin on admission. In all but one of these 15 patients, however, additional renal or cardiovascular abnormalities, or both, could be identified, which supported a multifactorial aetiology for lactic acidosis. Advanced age and cardiovascular and renal disease are absolute contraindications to the use of phenformin in diabetics.

Adolescent

Clinical and haemodynamic effects of minoxidil in refractory hypertension.

Thirteen patients whose hypertension had been resistant to conventional drug therapy, had minoxidil added to their regimen in doses from 5 to 60 mg/day. All responded with satisfactory reductions of blood pressure to mean values of 149/90mm Hg (supine) and 143/89mm Hg (standing). A significant portion of their previous antihypertensive therapy was either greatly decreased or withdrawn completely. Although fluid retention occurred in most patients as the dose of minoxidil was increased, this could be successfully checked by the use of diuretics. It was considered that in addition to beta-adrenoreceptor blocking drugs to control the reflexly induced cardiac stimulation, sufficiently aggressive diuretic therapy is mandatory to ensure the successful use of this drug. Haemodynamic evaluations in seven patients clearly showed that lowering of blood pressure was the result of decreases in peripheral vascular resistance as significant increases in the cardiac index occurred in all patients.

Adult

Morphological and immunological evidence of coagulopathy in renal complications of pregnancy.

Renal biopsies in 14 patients with P.E.T. or eclampsia showed constant I.F. reactions for IgM and fibrin, with frequent reactions for C1q and C3. The glomeruli showed reversible mesangial proliferation and swelling, with characterictic E.M. deposits, and segmental lesions were present in seven patients. Similar I.F. reactions occurred in three other patients with clinical diagnoses of P.E.T. whose biopsies demonstrated coexistent glomerular disease. Serum complement studies showed a significant rise in C3 in the third trimester of normal pregnancies and a further significant elevation in C1q and C3 in the third trimester of a series of unselected P.E.T. patients. In contrast, four patients from the biopsy series with eclampsia or severe P.E.T. showed profound depression of serum C3 and C4, at the time of maximum clinical severity, which was shown to return to normal in two patients. The I.F. findings confirm those of Petrucco et al (6), and, with the other data, suggest that immune-complex deposition and activation of the classical complement pathway could interrect with intravascular coagulation to produce the glomerular lesions of P.E.T. and eclampsia.

Adolescent