Treatment of immunoglobulin A nephropathy.

In this review, therapeutic trials for treatment of IgA nephropathy (Berger's disease) are reviewed and discussed. No disease-specific therapy exists. For treatment of hypertensive patients, angiotensin converting enzyme (ACE) inhibitors are preferred. They also decrease proteinuria and probably slow disease progression. However, there are still no controlled data on the effectiveness of ACE-inhibitors in the absence of hypertension or proteinuria. Renewed enthusiasm for treatment with fish oil arose after the publication of a randomized controlled trial in 1994 and long-term follow-up data of the trial cohort in 1998. Corticoid therapy in IgA nephropathy has been advocated for patients with nephrotic syndrome or crescentic disease. A recent non-randomised trial with long-term follow-up suggests that, in the presence of moderate proteinuria, corticosteroids may ameliorate renal function if administered before the creatinine clearance has decreased below 70 ml/min. Preliminary data suggest that mycophenolate mofetil (MMF) may reduce the risk of clinically significant IgA nephropathy recurring in kidney allografts. Many other promising treatment approaches have been tested, but in most instances results are insufficient for unequivocal conclusions. Several randomized controlled clinical trials are currently testing prednisone, fish oil, ACE-inhibitors, cyclophosphamide, MMF and vitamin E. In the absence of a disease-specific treatment, control of hypertension, proteinuria and probably dyslipidemia are pivotal. Chronic or recurrent infection including ton-sillitis should be treated effectively. Control of daily protein intake to 0.7-0.8 g/kg body weight may retard disease progression.

Afrocentricity: an emerging paradigm in social work practice.

Although several models of social work practice that can better assist people of color have emerged, the cultural values of this population generally have not been used as a theoretical base to develop new practice models. This situation not only prevents a truly diversified theoretical base in social work but also reinforces the hegemony of Eurocentric concepts for explaining and solving human and societal problems. Recently the concept "Afrocentricity" has been used to describe the cultural values of people of African descent. This article presents the values and describes the philosophical concepts of Afrocentricity as a social science paradigm on which social work practice can be conceived and built and explains the reasons for the emergence of an Afrocentric social science perspective. Social workers are encouraged to embrace the Afrocentric paradigm because of its emphasis on eliminating oppression and spiritual alienation.

Characterization of the adenosine receptor in microvascular coronary endothelial cells.

In the present work we studied the effect of adenosine and various adenosine analogues on cAMP level in guinea pig coronary endothelial cells of microvascular origin. The tested adenosine agonist mediate a concentration-dependent increase in cAMP level. The rank order of potency was 5'-N-ethylcarboxamidoadenosine (NECA) > CGS 21680 > N6-phenylisopropyladenosine (R-PIA) > 2-chloro-N6-cyclopentyladenosine (CCPA) which is typical for an adenosine A2 receptor. Their respective concentrations for half maximal stimulation of cAMP formation were 0.36 microM, 0.82 microM, 4.7 microM and 9.8 microM. The tested agonists showed differences in efficacy, NECA being the most efficacious. R-PIA, CCPA and adenosine were less efficacious, suggesting partial agonism. The efficacy of adenosine was unchanged by the addition of the nucleoside transport inhibitor S(4-nitrobenzyl)-6-thioinosine (NBTI, 10 microM) suggesting that inhibition of adenylyl cyclase through P-site activation is not responsible for the observed low efficacy of adenosine. We could demonstrate CGS 21680 activation of adenylyl cyclase in a peripheral receptor. We therefore suggest that the endothelial adenosine receptor resembles the striatal adenosine A2a receptor.

The effect of unlabelled monoclonal antibody (mAb) on the biodistribution of 131I-anti-idiotype mAb in murine B cell lymphoma.

The 38C13 murine B cell lymphoma model was used to study the effect of the preinjection of unlabelled anti-idiotype monoclonal antibody (mAb) on the subsequent biodistribution of 131I-anti-idiotype mAb. Mice with established tumors received 0-500 micrograms of unlabelled anti-idiotype mAb 24 h prior to the administration of 131I-anti-idiotype (specific), or both 125I-anti-idiotype and 131I-isotype-matched irrelevant control (nonspecific) mAb. Mice were counted daily in a gamma counter and sacrificed at 2-144 h following injection. Mice were dissected and the weight and activity of the animals and organs were measured. Mice were bled periodically and circulating idiotype levels were measured using an ELISA assay. Five hundred micrograms of unlabelled anti-idiotype mAb increased the retention time of the specific but not the nonspecific mAb in all organs and tumor. Following pretreatment with unlabelled mAb, the cumulative tumor/whole body and tumor/normal organ ratios became similar to those of the nonspecific mAb, with concentration ratios (specific/nonspecific mAb) of approximately 1, which persisted until 96 h post injection when circulating idiotype reappears in antigen excess. In the absence of unlabelled mAb there was less retention in tumor and normal tissue. This is presumed to be due in part to decreased levels of circulating 131I-mAb secondary to rapid plasma clearance of antigen-antibody complexes and tumor cell mediated dehalogenation, which results when the specific mAb specifically binds the targeted antigen. Thus, the addition of unlabelled mAb increased the retention by decreasing the specific behavior of the anti-idiotypic antibody.

Determinants of the antitumor effect of radiolabeled monoclonal antibodies.

The murine B-cell lymphoma 38C13 model was used to study the radiobiological effect of 131I-monoclonal antibody (MAB) therapy compared with dose equivalent external beam irradiation. Continuous exponentially decreasing low dose rate (LDR) gamma-irradiation, and multiply fractionated (MF) X-irradiation were compared with dose equivalent 131I-MAB. The relative therapeutic efficacy of radioimmunotherapy, and the relative contribution of (a) low dose rate; (b) whole body irradiation; and (c) microdosimetry to the overall effect were determined. Groups of mice with or without B-cell lymphoma were treated with either (a) 131I-anti-idiotype MAB; (b) 131I-isotype-matched irrelevant control MAB; (c) 5-15 Gy 250 kV X-irradiation given as a single fraction; (d) 2.5-30 Gy 250 kV X-irradiation given in 10 fractions/2 weeks; or by (e) continuous exponentially decreasing gamma-irradiation via a 137Cs source, which simulated the effective t1/2 of the 131I-MAB. In tumor-free mice the LD50/30 was approximately 10 Gy for MF and LDR external irradiation, and 11-12 Gy for 131I-MAB. However, the effect of these modes of irradiation on tumor size differed significantly. The cumulative percentage of tumor reduction averaged over 12 days was 0.635 +/- 0.055%/Gy for MF, and 1.36 +/- 0.061%/Gy for LDR external irradiation (a relative efficacy factor of 1.63 for LDR irradiation; P = 0.01). Assuming homogeneous body distribution, the tumor reduction effect over 12 days for 131I-MAB was 2.064 +/- 0.133%/Gy for specific, and 1.742 +/- 0.1%/Gy for nonspecific isotype-matched irrelevant 131I-MAB (P = 0.02). When 131I-MAB was compared to LDR external irradiation, the relative efficacy factor was 1.99 (P less than 0.001). In summary, there was a dose rate effect on tumor response, which may in part explain the efficacy of radioimmunotherapy. The additional effect of 131I-MAB on tumor response was only partially explained by the cumulative concentration ratio of 131I-MAB tumor/131I-MAB whole body, which was on average 1.7. This relatively low concentration ratio was partly due to tumor-mediated dehalogenation. Thus, the overall tumor response was a function of the total dose, dose rate, and both the specific and nonspecific distribution of 131I-MAB.