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Biomedical subjects

B Pussell

Publications and source records attributed to B Pussell.

9 recordsLinked to original sources

Reduced and standard target concentration tacrolimus with sirolimus in renal allograft recipients.

We report 6-month results of renal allograft recipients enrolled in seven Australian centers as part of a worldwide, multicenter, randomized, open-label, concentration-controlled trial comparing standard tacrolimus (sTAC) with reduced tacrolimus (rTAC) both with sirolimus (SRL) and steroids. Patients were randomized 1:1 to either rTAC (n = 33) with a target maintenance concentration of SRL of 8 to 15 ng/mL and TAC of 3 to 7 ng/mL, or sTAC (n = 31) with SRL target of 5 to 10 ng/mL and TAC of 8 to 12 ng/mL. Antibody induction was prohibited. Adult recipients of a first or second cadaveric or non-HLA-identical living donor renal graft were eligible for enrollment. Recipients with a panel-reactive antibody level of >50% and recipients of regrafts who had lost their first graft from rejection within the first 6 months were ineligible. The groups were compared for graft function, incidence of rejection, and patient and graft survival at 6 months. There were no differences in demographics. There were 30% and 29% discontinuations in the rTAC and sTAC groups mainly due to adverse events in the first month. The 6-month patient and graft survival by intention-to-treat analysis was 94% and 91% for rTAC and 100% and 97% for sTAC (P = NS), respectively. Incidence and severity of biopsy-proven acute rejection was not different between the two groups, being 21% for rTAC and 19% for sTAC. The mean serum creatinine was 121 micromol/L and 148 micromol/L for rTAC and sTAC groups (P =.09), respectively. Glomerular filtration rate (GFR) was 68 mL/min and 62 mL/min (P =.23), respectively. Adverse events, infections, and antihypertensive and antilipidemic agent usage were similar. Of interest is that the overall incidence of thrombotic microangiopathy was 14%. These results support the safety and efficacy of SRL + TAC. Reduced TAC is associated with a trend toward improved renal function.

Adult↗

Does non-enzymatic glycosylation affect complement function in diabetes?

We examined the role of non-enzymatic glycosylation in abnormalities of the complement system commonly found in Type 1 diabetes. Fourteen patients were found to have significantly increased levels of glycosylated C3 (p less than 0.001) and C4 (p less than 0.002) with levels of glycosylated C3 being higher than those of C4 (4.1 +/- 2.5% vs 0.8 +/- 0.8%). This correlated with the finding that in vitro, purified C3 was far more susceptible to this modification than C4. Autoradiography of limited trypsin digests of H3-glycosylated iC3 showed several sites were available for reaction. However, high levels of in vitro glycosylation had no significant effect on the haemolytic activity of C3 and C4, or the binding of iC3 to the CR1 receptor on erythrocytes. Further, IgG was similarly unaffected by non-enzymatic glycosylation in its ability to activate the complement pathway, or when present in an immune complex, to be dissociated from it by complement. We concluded that the immune complex-mediated damage implicated in some complications of Type 1 diabetes is unlikely to derive from any loss of complement function due to non-enzymatic glycosylation.

Antigen-Antibody Complex↗

Association of complement allotype C4B2 with anterior uveitis.

We have studied allotypes of the fourth component of complement (C4) in 44 patients with inflammatory eye disease in order to define genetic susceptibility factors further. Twenty-six patients had uveitis (18 had anterior uveitis) and 18 patients had retinal vasculitis. There was an increased incidence of the C4B2 allotype in patients with anterior uveitis (pc less than 0.002), especially in HLA B27 positive males. In contrast, there was no increased incidence of specific allotypes in patients with posterior uveitis or retinal vasculitis. This genetic association may form part of a disease susceptibility supratype in patients with anterior uveitis.

Alleles↗

Renal granulomatous angiitis--a case report.

A case of non-necrotizing granulomatous angiitis without significant glomerular pathology is described in a 61 yr-old female. The characteristic lesion consists of periarterial inflammation comprising a mixed population of mononuclear cells with prominent giant cell formation. There is no evidence of immunoglobulin, complement or fibrin deposition. It is concluded that this represents an unusual variant of polyarteritis nodosa which is apparently controlled by steroid therapy.

Female↗

Interpretation of tracer studies on plasma protein turnover: comparison of methods and optimization of techniques.

1. A comparison of several published methods for analysing plasma protein turnover data has been undertaken, with particular reference to rapidly metabolized proteins such as members of the complement series. 2. With the exception of the equilibrium time method, most methods proved adequate for the determination of overall fractional catabolic rates. A further exception is that the renal clearance method becomes invalid when the fractional catabolic rate approaches the renal iodide clearance, but this may be the method of choice for slowly metabolized proteins if accurate urine collections can be ensured. 3. For the measurement of the ratio of extra to intra-vascular protein pool size a clear preference emerged for the method of C. M. E. Matthews (1957, Physics in Medicine and Biology, 2, 36-53). For rapidly metabolized proteins the calculations must be preceded by a correction for the non-protein bound iodide retained in the intra- and extra-vascular spaces. 4. The accurate calculation of fractional catabolic rate in the extravascular pool generally requires more experimental data than are commonly collected as well as an accurate correction for non-protein bound label that remains unexcreted. Only two techniques hold promise of accurate results: Nosslin's rate equations method and a development of Vitek's deconvolution method described herein. Nosslin's integrated rate equations method is particularly affected by systematic errors in renal iodide clearance estimates and should probably not be further used for this purpose.

Blood Chemical Analysis↗

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.

Adult↗