We report a transfusion trial of platelets photochemically treated for pathogen inactivation using the synthetic psoralen amotosalen HCl. Patients with thrombocytopenia were randomly assigned to receive either photochemically treated (PCT) or conventional (control) platelets for up to 28 days. The primary end point was the proportion of patients with World Health Organization (WHO) grade 2 bleeding during the period of platelet support. A total of 645 patients (318 PCT and 327 control) were evaluated. The primary end point, the incidence of grade 2 bleeding (58.5% PCT versus 57.5% control), and the secondary end point, the incidence of grade 3 or 4 bleeding (4.1% PCT versus 6.1% control), were equivalent between the 2 groups (P ‫؍‬ .001 by noninferiority). The

A nucleic acid-targeted photochemical treatment (PCT) using amotosalen HCl (S-59) and ultraviolet A (UVA) light was developed to inactivate viruses, bacteria, protozoa, and leukocytes in platelet components. We conducted a controlled, randomized, double-blinded trial in thrombocytopenic patients requiring repeated platelet transfusions for up to 56 days of support to evaluate the therapeutic efficacy and safety of platelet components prepared with the buffy coat method using this pathogen inactivation process. A total of 103 patients received one or more transfusions of either PCT test (311 transfusions) or conventional reference (256 transfusions) pooled, leukoreduced platelet components stored for up to 5 days before transfusion. More than 50% of the PCT platelet components were stored for 4 to 5 days prior to transfusion. The mean 1-hour corrected count increment for up to the first 8 test and reference transfusions was not statistically significantly different between treatment groups (13 100 ؎ 5400 vs 14 900 ؎ 6200, P ‫؍‬ .11). By longitudinal regression analysis for all transfusions, equal doses of test and reference components did not differ significantly with respect to the 1-hour (95% confidence interval [CI], ؊3.1 to 6.1 ؋ 10 9 / L, P ‫؍‬ .53) and 24-hour (95% CI, ؊1.3 to 6.5 ؋ 10 9 /L, P ‫؍‬ .19) posttransfusion platelet count. Platelet transfusion dose, pretransfusion storage duration, and patient size were significant covariates (P < .001) for posttransfusion platelet counts. Clinical hemostasis, hemorrhagic adverse events, and overall adverse events were not different between the treatment groups. Platelet components prepared with PCT offer the potential to further improve the safety of platelet transfusion using technology compatible with current methods to prepare buffy coat platelet components. (Blood. 2003;101: 2426-2433)

The herbicide atrazine is one of the most commonly applied pesticides in the world. As a result, atrazine is the most commonly detected pesticide contaminant of ground, surface, and drinking water. Atrazine is also a potent endocrine disruptor that is active at low, ecologically relevant concentrations. Previous studies showed that atrazine adversely affects amphibian larval development. The present study demonstrates the reproductive consequences of atrazine exposure in adult amphibians. Atrazineexposed males were both demasculinized (chemically castrated) and completely feminized as adults. Ten percent of the exposed genetic males developed into functional females that copulated with unexposed males and produced viable eggs. Atrazineexposed males suffered from depressed testosterone, decreased breeding gland size, demasculinized/feminized laryngeal development, suppressed mating behavior, reduced spermatogenesis, and decreased fertility. These data are consistent with effects of atrazine observed in other vertebrate classes. The present findings exemplify the role that atrazine and other endocrine-disrupting pesticides likely play in global amphibian declines.A trazine is one of the most widely used pesticides in the world. Approximately 80 million pounds are applied annually in the United States alone, and atrazine is the most common pesticide contaminant of ground and surface water (1). Atrazine can be transported more than 1,000 km from the point of application via rainfall and, as a result, contaminates otherwise pristine habitats, even in remote areas where it is not used (2, 3). In fact, more than a half million pounds of atrazine are precipitated in rainfall each year in the United States (2).In addition to its persistence, mobility, and widespread contamination of water, atrazine is also a concern because several studies have shown that atrazine is a potent endocrine disruptor active in the ppb (parts per billion) range in fish (4, 5), amphibians (6-12), reptiles, and human cell lines (5, 13-15), and at higher doses (ppm) in reptiles (16-18), birds (19), and laboratory rodents (20-28). Atrazine seems to be most potent in amphibians, where it is active at levels as low as 0.1 ppb (6-10). Although a few studies suggest that atrazine has no effect on amphibians under certain laboratory conditions (29,30), in other studies, atrazine reduces testicular volume; reduces germ cell and Sertoli cell numbers (11); induces hermaphroditism (6, 8, 10); reduces testosterone (10); and induces testicular oogenesis (7-9, 31). Furthermore, atrazine contamination is associated with demasculinization and feminization of amphibians in agricultural areas where atrazine is used (32) and directly correlated with atrazine contamination in the wild (7,9,33,34).Despite the wealth of data from larvae and newly metamorphosed amphibians, the ultimate impacts of atrazine's developmental effects on reproductive function and fitness at sexual maturity, which relate more closely to population level effects and amphibian declines, have b...

Developmental plasticity is found in most organisms, but its role in evolution remains controversial. Environmentally induced phenotypic differences may be translated into adaptive divergence among lineages experiencing different environmental conditions through genetic accommodation. To examine this evolutionary mechanism, we studied the relationship between plasticity in larval development, postmetamorphic morphology, and morphological diversity in spadefoot toads, a group of closely related species that are highly divergent in the larval period and body shape and are distributed throughout temperate areas of both the New and the Old World. Previous studies showed that accelerated metamorphosis is adaptive for desert-dwelling spadefoot toads. We show that even under common garden conditions, spadefoot toad species show divergent reaction norms for the larval period. In addition, experimentally induced changes in the larval period caused correlated morphological changes in postmetamorphic individuals such that long larval periods resulted in relatively longer hindlimbs and snouts. A comparative analysis of morphological variation across spadefoot toad species also revealed a positive correlation between the larval period and limb and snout lengths, mirroring the effects of within-species plasticity at a higher taxonomic level. Indeed, after Ϸ110 Ma of independent evolution, differences in the larval period explain 57% of the variance in relative limb length and 33% of snout length across species. Thus, morphological diversity across these species appears to have evolved as a correlated response to selection for a reduced larval period in desert-dwelling species, possibly diverging from ancestral plasticity through genetic accommodation.allometry ͉ genetic accommodation ͉ life-history evolution ͉ morphological diversity ͉ larval period

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