Description of hypersensitivity adverse events following administration of heparin that was potentially contaminated with oversulfated chondroitin sulfate in early 2008.

PURPOSE: To characterize the nature of a heparin contaminant's clinical effects in cases reported to the Adverse Event Reporting System (AERS). The FDA received reports of heparin-associated adverse events (AEs) starting in late 2007-early 2008 during a national investigation of allergic-type events. The investigation identified Baxter Healthcare-brand heparin product due to its strongest association with the events. Later, oversulfated chondroitin sulfate (OSCS), a heparin-like contaminant, was discovered. METHODS: This study was a case series of heparin reports in AERS received 1 January 2008 to 31 March 2008. Variables considered were frequency of treatment settings, AEs, mortality; as well as heparin dose and OSCS contamination. RESULTS: Five hundred seventy-four AERS cases (unduplicated reports) were identified and included. Of 94 cases with a fatal outcome, 68 reported at least one AE term from the list used to identify an allergic-type event. Nearly 75% of AEs in cases of IV administration (n = 170/233) reportedly occurred within 10 minutes, whereas over half of subcutaneous administration cases (n = 13/23) resulted in times-to-event of greater than 24 hours. Although cases with a time-to-event of less than 10 minutes appeared to correlate with higher levels of OSCS contamination, no clear differences were noted between high- and low-to-absent OSCS concentration lots with respect to AEs observed. CONCLUSIONS: Intravenous administration and a higher OSCS concentration appeared to correlate with a more rapid onset of event. The FDA continues to monitor AEs associated with heparin use and has taken appropriate regulatory action to ensure a safe heparin drug supply.

A direct observation technique for evaluating sclerotium germination by Macrophomina phaseolina and effects of biocontrol materials on survival of sclerotia in soil.

Germination of sclerotia of Macrophomina phaseolina was quantified by direct microscopic observation following application of experimental treatments in vitro and incubation of sclerotia in soil. To assay germination, pieces of agar containing sclerotia were macerated in dilute, liquid cornmeal agar on glass slides; thinly spread; and incubated in a saturated atmosphere for 18-22 h. Germinated sclerotia then were identified by morphological features of germ hyphae. Frequencies of germination were similar in three dilute agar media. Germination was not affected by air-drying sclerotia for 2 weeks, but it was significantly reduced after 4 weeks and greatly reduced or eliminated after 6 or 8 weeks. Survival of sclerotia for 14 days in soil was greatest at 50, 75, and 100% moisture-holding capacity, less at 0 and 25%, and least at 125% (flooded soil). Incorporation of ground poultry litter into soil at 5% by weight reduced survival of sclerotia after 13 days, and incorporation of litter at 10% nearly eliminated it. These results indicate that the direct-observation technique may be used to evaluate animal wastes and other agricultural byproducts for biocontrol activity against sclerotia of M. phaseolina in soil.

Enhancement of sporulation in species of Bipolaris, Curvularia, Drechslera, and Exserohilum by growth on cellulose-containing substrates.

Nine species of Bipolaris, Curvularia, Drechslera, and Exserohilum were compared for sporulation on agar media and for enhancement of sporulation by growth on four cellulose-containing substrates (index card, filter paper, cheesecloth, cotton fabric). On two natural and one synthetic agar media, sporulation varied from profuse to nonexistent among three isolates of each species. Growth of all species on cellulose substrates resulted in large and significant increases in sporulation. Growth on index card pieces often provided the greatest increases, but no single substrate was superior for all species, and significant substrate x isolate interactions were observed within species. Overlay of filter paper onto whole colonies in agar plates resulted in 2 to 18-fold increases in sporulation for eight of nine species and production of spores in sufficient quantity for most experimental purposes. Overlay of soil dilution plates with filter paper to promote sporulation of colonies enabled detection of B. spicifera, B. hawaiiensis, C. lunata, and E. rostratum at relatively low population levels (< or =1.3 x 10(3) colony-forming units per gram of soil) in samples of a naturally infested soil. Results indicate that enhancement of sporulation by growth of species of Bipolaris, Curvularia, Drechslera, and Exserohilum on cellulose substrates may facilitate (i) their identification in culture, (ii) production of spores at relatively high concentrations, and (iii) detection and enumeration of these fungi in soil.