Serum L-arginine in hypercholesterolaemia.
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Biomedical subjects
Publications and source records attributed to D A Oleesky.
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A rapid vacuum-driven procedure, using pre-treated Sep-Pak C18 cartridges, has been developed for the simultaneous extraction of arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) from plasma. Non-specific interference was removed by fractional elution with an aqueous methanol/trifluoroacetic acid (TFA) mixture. AVP and ANP were coeluted under positive pressure with a methanol/TFA mixture and the eluates air-dried before measurement using separate radioimmunoassays. Assay ranges for AVP and ANP were 0.12-29.5 pmol/L and 0.65-162 pmol/L, respectively, with mean recoveries (standard deviation in parentheses) for AVP of 96.4% (5.5%) at a level of 11.8 pmol/L and for ANP of 94.8% (5.9%) at a level of 32.4 pmol/L. The extraction and assay procedures were validated by observing the changes in plasma AVP and ANP concentrations in normal subjects at different stages of hydration and in elderly patients during treatment for congestive cardiac failure.
Terminal complement complex (TCC) and C1r-C1s-C1 inhibitor complex (C1/C1 INH) concentrations were measured in plasma and synovial fluid from patients with arthritis and related to other measures of disease activity. Both TCC and C1/C1 INH concentrations were significantly increased in patients with rheumatoid arthritis (RA) compared with patients with osteoarthritis (plasma and synovial fluid, P less than 0.05) and normal subjects (plasma only, P less than 0.001). In the patients with RA, there was no correlation between plasma or synovial fluid TCC concentrations and IgM rheumatoid factor, immune complex or C1/C1 INH levels. However, in 10 patients with seronegative RA, C1/C1 INH and immune complex levels correlated significantly in synovial fluid (r = 0.69, P less than 0.05) although not in plasma (r = 0.52). Plasma and synovial fluid TCC and C1/C1 INH concentrations did not differ in rheumatoid patients with severe compared with mild joint disease (categorized by the Ritchie score). These results confirm a role for complement activation in RA but suggest that several mechanisms are involved in its pathogenesis.
An unusual case of salt-wasting in a male infant is reported. The cause was a small X-chromosomal deletion within Xp21 resulting in the syndrome of congenital adrenal hypoplasia with glycerol kinase deficiency. This syndrome can readily be diagnosed by routine biochemical tests.
The potential role of complement activation and the membrane attack complex in the pathogenesis of Graves' disease and Hashimoto's thyroiditis has been investigated by measuring serum concentrations of the C1r-C1s-C1 inhibitor complex (C1/C1-inh) and the terminal complement complex (TCC), and by studying the binding to thyroid tissue of monoclonal and polyclonal antibodies against TCC neoantigens. Serum C1/C1-inh and TCC concentrations were significantly increased in 29 patients with untreated Graves' disease compared with 47 healthy subjects (P less than 0.001 for both), and decreased significantly after carbimazole treatment in 18 of these patients for whom post-treatment samples were available (P less than 0.01 and P less than 0.02, respectively). The serum TCC concentration, but not that of C1/C1-inh, was also significantly increased in 15 patients with Hashimoto's thyroiditis compared with the 47 healthy subjects (P less than 0.001). TCCs were identified by immunohistochemical staining around the thyroid follicles in thyroidectomy specimens from patients with Graves' disease (six out of six) and Hashimoto's thyroiditis (two out of two); normal thyroid tissue from two subjects showed no staining. These results suggest a role for complement, in particular the membrane attack complex in the pathogenesis of autoimmune thyroid disease.
C9, the terminal component of complement, is the key part of the membrane attack complex formed as a result of complement activation; it has also been reported to be an acute phase protein. Its potential role in Graves' disease has been studied by measuring plasma C9 concentrations using an automated two-site immunoradiometric assay employing monoclonal antibodies, whose binding to thyroid tissue has also been investigated. The plasma C9 concentration in patients with hyperthyroid Graves' disease (86.3 +/- 21.6 mg/l, mean +/- SD; n = 49) was significantly increased (P less than 0.001) compared with normal subjects (60.4 +/- 13.4 mg/l; n = 48). In contrast, the plasma concentration of C-reactive protein, a marker of the acute phase response, was not significantly different between the two groups. The plasma C9 concentration in patients with hyperthyroid Graves' disease decreased significantly (P less than 0.01) after treatment with antithyroid drugs (carbimazole or methimazole; n = 14), but not after radioactive iodine (131I) treatment (n = 18). Immunohistochemical staining demonstrated that monoclonal antibody to C9 bound to the basement membranes of thyroid follicular cells of Graves' thyroid tissue but not to normal thyroid tissue. Radiolabelled monoclonal antibody to C9 bound to membrane fragments prepared from thyroid glands from two patients with Graves' disease. We conclude that C9, and by implication the membrane attack complex, may be involved in the pathogenesis of Graves' disease.
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The performance of the dexamethasone suppression test (DST) was investigated in 45 female anorexic out-patients (cross-sectional study) and in nine female anorexic in-patients (longitudinal study). DST non-suppression was strongly associated with negative energy balance (low body weight and low Ponderal Index) but there was no significant association with the presence of affective or neurotic disturbance in these patients. These findings cast doubt on the value of the DST in the management of depressive illness.