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Biomedical subjects

C G Winearls

Publications and source records attributed to C G Winearls.

At least 91 records · Page 5Linked to original sources

Recurrence of circulating anti-glomerular basement membrane antibody three years after immunosuppressive treatment and plasma exchange.

A patient with auto-antibody mediated Goodpasture's syndrome was successfully treated with cytotoxic drugs, steroids and plasma exchange. After an absence of three years, circulating anti-glomerular basement membrane antibodies reappeared, and linear IgG staining of the glomeruli was shown by immunofluorescent studies. Renal function did not change and there was no evidence of pulmonary hemorrhage. Antibody levels then fell spontaneously over the succeeding 18 months.

Adult↗

Cardiovascular abnormalities in osteogenesis imperfecta.

To investigate the prevalence of cardiac abnormalities in osteogenesis imperfecta we performed a clinical and echocardiographic study on 20 patients. One patient had aortic regurgitation, 13 had soft late apical systolic murmurs (without significant mitral regurgitation), and seven had systemic hypertension. In only one patient was there echocardiographic evidence of mitral valve prolapse. The aortic root diameter exceeded the normal range in six patients, two of whom were hypertensive. The overall mean value (+/- 1 S.D.) in the 16 patients without marked skeletal deformity was 2.02 +/- 0.33 cm/m2. The echocardiographic appearances suggested that the left-sided valve cusps were thin, and in 13 patients the aortic valve leaflets showed a coarse systolic flutter.

Adolescent↗

Clinical usefulness of urinary 3-methylhistidine excretion in indicating muscle protein breakdown.

Urinary excretion of the post-translationally modified amino-acid 3-methylhistidine, derived from the contractile proteins actin and myosin, was measured in patients with conditions associated with nitrogen loss. The ratio of 3-methylhistidine:creatinine excretion, a measure of the fractional catabolic rate of myofibrillar protein was increased in severe injury, thyrotoxicosis, neoplastic disease, prednisolone administration, and sometimes Duchenne muscular dystrophy. In myxoedema, osteomalacia, and hypothermia the ratio was decreased; and starvation, elective operations, and rheumatoid arthritis had little effect. Provided that the diet is meat free, measurement of urinary 3-methylhistidine may provide useful information on the cause of protein loss.

Adolescent↗

Interstitial nephritis.

The clinical and pathological findings are reviewed in ten cases where renal biopsy showed abnormalities predominantly within the interstitium. In six the nephritis was considered to be drug-induced; in two the aetiology was slightly obscure but the most likely diagnosis was considered to be sarcoidosis. Of the remaining two cases one was chronic pyelonephritis and the other polyarteritis nodosa. The diagnosis and pathogenesis of the renal lesions are discussed and attention is drawn to the importance of distinguishing primary interstitial changes from those found in association with glomerular disease.

Adolescent↗

Passive enhancement and hyperacute rejection of renal allografts in the rat.

Attempts to induce passive enhancement of renal allografts with donor-specific cytotoxic antibody can result in antibody-mediated damage to the grafted organ. Hyperacute renal allograft rejection occurred in the homozygous DA to Lewis strain combination when Lewis anti-DA serum was administered with guinea pig complement. Hyperacute rejection was prevented in four of five rats when Lewis anti-DA F(ab')2 was injected before the administration of Lewis anti-DA serum and complement and these grafts had enhanced survival. Red blood cell absorption of the Lewis anti-DA serum to produce an anti-Ia-like serum, also removed its ability to produce hyperacute rejection without removing its ability to enhance. With appropriate modifications both of these techniques would be applicable to human transplantation.

Absorption↗

Vein allografts for arterial replacement in rats: an immunological and histological study.

Vein allografts were studied in the rat using the major histocompatibility complex-incompatible DA and Lewis inbred strains. Allografts were performed in the Lewis to DA and DA to Lewis combinations, with Lewis to Lewis isografts serving as controls. Vein grafts were performed by interposing a 1 cm length of fresh iliolumbar vein into a defect of the iliac artery, using microsurgical techniques. The grafts were under observation for 18 weeks for (1) patency, (2) gross structural changes, (3) histological changes, and (4) antibody responses. No immunosuppression was used. All grafts remained patient throughout the period of observation, although aneurysm formation was noted in some allografts toward the end of the observation period. Histologically, allografts and isografts were indistinguishable. In the first 2 weeks, they showed patchy areas of necrosis in the vein walls, with subsequent intimal hyperplasia and medial fibrosis. In both strain combinations a lymphocytotoxin response was induced in most animals, the response being particularly strong in the DA to Lewis combination. All cytotoxic activity could be absorbed out using red blood cells, suggesting that the specificity of the antibody was mainly or entirely directed against SD antigens.

Animals↗

A quantitative comparison of whole antibody and F(ab')2 in kidney allograft enhancement.

Whole antiserum, IgG, and a greater than 99% pure F(ab')2 preparation were compared for their ability to enhance Lewis renal allografts in DA recipients. Despite having unimpaired antigen-binding capacity, the DA anti-Lewis F(ab')2 was virtually ineffective at the highest dose tested, and was calculated to be a minimum of 100 times less effective than whole antibody. The administration of a 10-fold excess of F(ab')2 before an effective dose of IgG did not block the enhancing effect of the latter.

Animals↗

Use of cyclophosphamide and enhancing serum to suppress renal allograft rejection in the rat.

Cyclophosphamide was tested for its interaction with passive enhancement in suppressing the rejection of kidney allografts in the (DA x Lewis)F1 to Lewis rat strain. Dose response studies with cyclophosphamide showed that 10 mg/kg/day for 14 days was necessary for complete suppression of rejection and indefinite graft survival. Doses of 5 and 3.5 mg/kg/day had only a marginal effect on graft function and survival, although the lymphocytotoxin response to the graft was completely or very substantially suppressed by these smaller doses. The use of passive enhancement with cyclophosphamide at the 5- and 3.5-mg/kg/day doses resulted in a favourable interaction with improved graft function and survival. Interestingly, passive enhancement in combination with 5 mg/kg/day of cyclophosphamide resulted in indefinite graft survival only if cyclophosphamide was given for 28 days. If cyclophosphamide was given for 14 days, rejection was suppressed only during the period of cyclophosphamide treatment.

Animals↗

The combined use of antilymphocyte serum and cyclophosphamide to suppress renal allograft rejection in the rat.

Cyclophosphamide and antilymphocyte serum (ALS) were compared for their ability to suppress renal allograft rejection in the rat. These two agents were chosen since they are generally considered to act on different arms of the immune response, and might therefore complement each other's action. Dose response studies showed that both agents could suppress rejection completely. There were no differences in their ability to suppress the lymphocytotoxic antibody response to the graft and the histological patterns of rejection were similar. There was no evidence that cyclo-phosphamide was more effective in suppressing vascular lesions. The doses of both agents which suppressed the lymphocytotoxic antibody response were substantially lower than those required to suppress graft rejection. When suboptimal doses of the two agents were administered together, the combinations were found to be additive and not synergistic.

Animals↗