The ascomycin macrolactam pimecrolimus (Elidel, SDZ ASM 981) is a potent inhibitor of mediator release from human dermal mast cells and peripheral blood basophils.

BACKGROUND: The ascomycin macrolactam pimecrolimus (Elidel, SDZ ASM 981) has recently been developed as a novel and cell-selective inhibitor of inflammatory cytokine secretion; it has fewer adverse effects than currently available drugs. OBJECTIVE: In this study, we investigated the capacity of pimecrolimus to directly inhibit in vitro mediator release from human skin mast cells and basophils. METHODS: Purified cutaneous mast cells or basophil-containing peripheral blood leukocytes were obtained from healthy human donors and preincubated with pimecrolimus (0.1 nmol/L to 1 micromol/L) in the absence or presence of its specific antagonist (rapamycin), cyclosporin A (100 nmol/L to 1 micromol/L), or dexamethasone (1 micromol/L) and then stimulated with anti-IgE or with calcium ionophore A23187 plus phorbol myristate acetate. Cell supernatants were kept for analysis of histamine, tryptase, LTC4, and TNF-alpha. RESULTS: Pimecrolimus caused a strong and dose-dependent inhibition of anti-IgE--induced release of histamine from mast cells and basophils (maximally 73% and 82%, respectively, at 500 nmol/L pimecrolimus) and of mast cell tryptase (maximally 75%) and a less pronounced inhibition of LTC4 (maximally 32%) and of calcium ionophore plus phorbol myristate acetate--induced mast cell TNF-alpha release (90% maximum at 100 nmol/L pimecrolimus). In contrast, inhibition achieved during mast cell histamine release was maximally 60% with cyclosporin A and only 28% with dexamethasone. CONCLUSION: These data demonstrate a marked inhibitory capacity of pimecrolimus on mediator release from human mast cells and basophils with a potency exceeding that of cyclosporin A and dexamethasone. Pimecrolimus might thus be expected to be effective in the treatment of mast cell-- and basophil-dependent diseases.

Knowledge and attitudes of home care nurses toward hospice referral.

OBJECTIVE: Nurses and administrators are concerned with removing barriers to appropriate and cost-effective referrals between programs. The goal of this research was to describe knowledge and attitudes of home care nurses toward hospice referral. BACKGROUND: The literature review did not identify studies related to the referral of patients from traditional home care to hospice programs. A few studies related to the hospice referral processes suggested issues with conflicts between programs, attitude barriers to open communications, issues regarding late hospice referrals, and practitioner reluctance to "give up" patients with whom they had established relationships. METHOD: This study used a descriptive, quantitative method. A 15-item, self-administered survey was developed by the investigators and hospice administrators. It was distributed to 160 registered nurses employed as full- or part-time staff in a large midwestern home care agency. Completed surveys were returned by 75 nurses, for a response rate of 46.9% (N = 75). RESULTS: Nurses perceived that home care and hospice services were very similar; they resisted hospice referral as long as they felt that services could be provided adequately by home care; they desired to maintain patient continuity and special rapport and demonstrated inconsistent knowledge regarding hospice referral criteria and relative costs. CONCLUSIONS: Nurses in different programs would benefit from improved communication links, accurate cross-program information, and development of increased trust relationships. Improvements in communication and transition programs for patients and families should include structural and programmatic changes.