Advance care planning among hematopoietic cell transplant patients and bereaved caregivers.

Younger, healthier patients contemplating high-risk (but potentially curative) hematopoietic cell transplants (HCT) may not consider advance care planning (ACP). We investigated the effect of pre transplant ACP in surviving HCT patients and bereaved caregivers using retrospective, audiotaped telephone surveys. Subjects were identified between 2001 and 2003 via databases at two high-volume HCT centers. Transcripts were coded by two investigators, with differences resolved by consensus. HCT survivors (n=18) were interviewed a median of 13 months after HCT for acute leukemia (7), lymphoma (5) or other (6); 50% had living wills, 72% had a formal proxy. Twelve (67%) had discussed mortality risk pre HCT with the medical team. Of those, 92% felt their hope and perception of the medical team's truthfulness was increased or unchanged (I/U) by the conversation, whereas all felt clinician commitment to transplant was I/U. Bereaved caregivers (n=11) were interviewed a median of 10 months post death (median 31 days post HCT, range 13-152). Nine (82%) had discussed mortality risk pre-HCT with the medical team; 7 (78%) felt hope was I/U, all felt clinician commitment to transplant and truthfulness was I/U, and most felt ACP reduced burden (67%). ACP discussions with patients and caregivers pre-HCT did not affect hope and supported confidence in medical teams.

A novel assay for fungal ketol-isomerase activity.

2-Deoxy-D-glucose-6-phosphate ketol-isomerase (EC 2.6.1.16) forms glucosamine-6-phosphate and glutamate from fructose-6-phosphate and glutamine and plays an important role in chitin synthesis in fungi. We have established a new assay for fungal ketol-isomerase activity that is amenable to high throughput screening to identify enzyme inhibitors. Aspergillus fumigatus crude lysate was incubated with substrates and after incubation, reactions were terminated. Glutamate dehydrogenase, nitro blue tetrazolium chloride, phenazine methosulfate and beta-NAD were added and the amount of glutamate formed by ketol-isomerase activity was determined by measuring OD585nm. A feedback inhibitor, UDP-N-acetylglucosamine, of fungal ketol-isomerase was successfully detected by this assay (IC50=0.48 mM). In a pilot scale screening, an active extract from an extremophilic bacterium was found, and the extract showed antifungal activity against A. fumigatus, Candida albicans and C. glabrata.

Three new peroxides from the sponge Plakinastrella species.

Two new five-membered-ring peroxide acids, plakinic acid F (3) and epiplakinic acid F (4), and a new peroxide-lactone, plakortolide F (5), were isolated from a sponge of the genus Plakinastrella collected from Felicite Island, Seychelles. The structures were elucidated through spectral analysis. The free acids 3 and 4 exhibit moderate antifungal activity against Candida albicans with minimum inhibitory concentrations of 25 micrograms/mL (SDB) and 3.1 micrograms/mL (RPMI) for 3, and 25 micrograms/mL (SDB) and 6.25 micrograms/mL (RPMI) for 4, respectively. Both also showed moderate in vitro inhibition of Aspergillus fumigatus with IC90's of 25 micrograms/mL.