A monoclonal antibody against GBM heparan sulfate induces an acute selective proteinuria in rats

A monoclonal antibody against GBM heparan sulfate induces an acute selective proteinuria in rats. After immunization of mice with partially-purified heparan sulfate proteoglycan (HSPG) isolated from rat glomeruli, a monoclonal antibody (mAb JM-403) was obtained, which was directed against heparan sulfate (HS), the glycosaminoglycan side chain of HSPG. In ELISA it reacted with isolated human glomerular basement membrane (GBM) HSPG, HS and hyaluronic acid, but not with the core protein of human GBM HSPG, and not with chondroitin sulfate A and C, dermatan sulfate, keratan sulfate and heparin. Furthermore, it did not bind to laminin, collagen type IV or fibronectin. Specificity of JM-403 for HS was also suggested by results of inhibition studies, which found that intact HSPG and HS, but not the core protein, inhibited the binding of JM-403 to HS. In indirect immunofluorescence on cryostat sections of rat kidney, a fine granular to linear staining of the GBM was observed, along with a variable staining of the other renal basement membranes. Pretreatment of the sections with heparitinase completely prevented the binding of mAb JM-403, whereas pretreatment with chondroitinase ABC or hyaluronidase had no effect. The precise binding site of mAb JM-403 was investigated by indirect immunoelec-tron microscopy. It revealed a diffuse staining of the whole width of the GBM. One hour after intravenous injection of JM-403 into rats, the mAb was detected along the glomerular capillary wall in a fine granular pattern, which shifted towards a more mesangial localization after 24 hours. No binding was observed anymore by day 15. Intravenous injection induced a dose-dependent, transient and selective proteinuria that was maximal immediately after the injection. Administration of 2 mg of JM-403 increased the urinary albumin excretion within the first 24 hours after injection from (mean ± SD) 177 ± 19 to 20,755 ± 10,310 µg/24 hr (P < 0.01); the urinary IgG excretion increased from 5.8 ± 2.9 to 236.1 ± 132.2 µg/24 hr (P < 0.03); the selectivity index (clearance IgG/clearance albumin) decreased from 0.33 ± 0.12 to 0.12 ± 0.05 (P < 0.004)

Preventive home care of frail older people: a review of recent case management studies.

Preventive actions targeting community-dwelling frail older people will be increasingly important with the growing number of very old and thereby also frail older people. This study aimed to explore and summarize the empirical literature on recent studies of case/care management interventions for community-dwelling frail older people and especially with regard to the content of the interventions and the nurse's role and outcome of it. Very few of the interventions took either a preventive or a rehabilitative approach using psycho-educative interventions focusing, for instance, on self-care activities, risk prevention, health complaints management or how to preserve or strengthen social activities, community involvement and functional ability. Moreover, it was striking that very few included a family-oriented approach also including support and education for informal caregivers. Thus it seems that the content of case/care management needs to be expanded and more influenced by a salutogenic health care perspective. Targeting frail older people seemed to benefit from a standardized two-stage strategy for inclusion and for planning the interventions. A comprehensive geriatric assessment seemed useful as a base. Nurses, preferably trained in gerontological practice, have a key role in case/care management for frail older people. This approach calls for developing the content of case/care management so that it involves a more salutogenic, rehabilitative and family-oriented approach. To this end it may be useful for nurses to strengthen their psychosocial skills or develop close collaboration with social workers. The outcome measures examined in this study represented one of three perspectives: the consumer's perspective, the perspective of health care consumption or the recipient's health and functional ability. Perhaps effects would be expected in all three areas and thus these should be included in evaluative studies in addition to measures for family and/or informal caregiver's strain and satisfaction