Efficacy of prophylactic transfusions using single donor apheresis platelets versus pooled platelet concentrates in AML/MDS patients receiving allogeneic hematopoietic stem cell transplantation.

Superiority of single-donor apheresis platelets (SDAP) over pooled platelet concentrates (PPC) transfusions is largely assumed, but unproven. We hypothesized that prophylactic SDAP and PPC transfusions are clinically equivalent after allogeneic hematopoietic stem cell transplants (HSCT). We studied all transfusions administered to 33 patients with AML/MDS during the first 100 days after busulfan-based, myeloablative HSCT. All donor-recipient pairs were ABO identical. Transfusion threshold was a platelet count < or =15 x 10(9)/l. The corrected increment (CCI) was used for all comparisons. Median time to platelet engraftment was 13 days (n=30). PPC transfusions (n=105) were ABO compatible, while 10% of 41 SDAP were not (P=0.006). Median post-transfusion platelet count was 51K/microl (5-118K) after SDAP and 36K/microl (3-115K) after PPC (P=0.0004). Median CCI was 14.178 (SDAP) versus 7.793 (PPC) (P=0.0001). Median time to another transfusion was 3 days (SDAP) and 2 days (PPC; P=0.3). In the week following any given transfusion, the median number of new transfusions was similar (n=2), as well as the need of further transfusion (16 versus 24%, P=0.2). A total of 17% of SDAP and 30% of PPC transfusions were labeled 'ineffective' (P=0.1). There were two non-lethal hemorrhage episodes (6%). SDAP transfusions produced better platelet counts, but SDAP and PPC were equally effective in preventing hemorrhage.

Identifying primary stressors impacting macroinvertebrates in the Salinas River (California, USA): relative effects of pesticides and suspended particles.

Laboratory dose-response experiments with organophosphate and pyrethroid pesticides, and dose-response experiments with increasing particle loads were used to determine which of these stressors were likely responsible for the toxicity and macroinvertebrate impacts previously observed in the Salinas River. Experiments were conducted with the amphipod Hyalella azteca, the baetid mayfly Procloeon sp., and the midge Chironomus dilutus (Shobanov, formerly Chironomus tentans). The results indicate the primary stressor impacting H. azteca was pesticides, including chlorpyrifos and permethrin. The mayfly Procloeon sp. was sensitive to chlorpyrifos and permethrin within the range of concentrations of these pesticides measured in the river. Chironomus dilutus were sensitive to chlorpyrifos within the ranges of concentrations measured in the river. None of the species tested were affected by turbidity as high as 1000 NTUs. The current study shows that pesticides are more important acute stressors of macroinvertebrates than suspended sediments in the Salinas River.

Efficacy and safety of prolonged thromboprophylaxis with a low molecular weight heparin (dalteparin) after total hip arthroplasty--the Danish Prolonged Prophylaxis (DaPP) Study.

The aim of this study was to compare the efficacy and safety of prolonged (35 days) thromboprophylaxis with a standard length (7 days) regimen of a low molecular weight heparin in patients undergoing total hip arthroplasty. The study was multicentre, randomised, double-blind, and prospective with two groups. Following seven days on a standard length regimen of dalteparin (5000 antifactor Xa units subcutaneously once daily starting 12 h before surgery), patients were randomized to continue the prophylaxis with either subcutaneous injections of dalteparin or placebo injections for a further 28 days. Efficacy was evaluated at the end of the study (day 35) in all patients with bilateral ascending phlebography to detect deep vein thrombosis. Bleeding complications and other adverse events were registered throughout the study period. Three hundred consecutive patients agreed to participate before the operation: 281 were finally randomised and 215 completed the study; two patients died before randomisation; 17 developed deep vein thrombosis; none developed pulmonary embolism; and five of 113 patients (4.4%, 95% CI 1-10%) developed deep vein thrombosis in the dalteparin group, compared with 12 of 102 (11.8%; 95% CI 6-20%) in the placebo group (p=0.039). Deep vein thrombosis in the proximal veins was diagnosed in one patient (0.9%; 95% CI 0-5%) in the dalteparin group, and in five (5.0%; 95% CI 2-11%) in the placebo group (p=0.076). Major bleeding was observed in one patient in the placebo group; minor bleeding complications and adverse events were equally distributed between the groups. We concluded that prolonged (35 days) thrombo prophylaxis with dalteparin is more effective than a standard length (7 days) regimen without increased risk of bleeding complications or other adverse events.

In vitro biosynthesis of fatty acids inDrosophila melanogaster.

A new in vitro technique, utilizing ruptured larvae ofDrosophila melanogaster, was employed to study the incorporation of(3)H-acetate into long-chain fatty acids. Preparative gas-liquid chromatography and scintillation spectroscopy were used to determine the relative activity of each fatty acid from total lipid extracts. Quantitative changes were observed in the distribution of label during the course of the incubation times, which ranged from five minutes to nine hours. All fatty acids which were observed to incorporate acetate in previous in vivo studies also showed incorporation of label under these in vitro conditions. It is concluded that this system may be useful for studying aspects on insect metabolism for short intervals of time.

Integrated assessment of the impacts of agricultural drainwater in the Salinas River (California, USA).

The Salinas River is the largest of the three rivers that drain into the Monterey Bay National Marine Sanctuary in central California. Large areas of this watershed are cultivated year-round in row crops and previous laboratory studies have demonstrated that acute toxicity of agricultural drainwater to Ceriodaphnia dubia is caused by the organophosphate (OP) pesticides chlorpyrifos and diazinon. In the current study, we used a combination of ecotoxicologic tools to investigate incidence of chemical contamination and toxicity in waters and sediments in the river downstream of a previously uncharacterized agricultural drainage creek system. Water column toxicity was investigated using a cladoceran C. dubia while sediment toxicity was investigated using an amphipod Hyalella azteca. Ecological impacts of drainwater were investigated using bioassessments of macroinvertebrate community structure. The results indicated that Salinas River water downstream of the agricultural drain is acutely toxic to Ceriodaphnia, and toxicity to this species was highly correlated with combined toxic units (TUs) of chlorpyrifos and diazinon. Laboratory tests were used to demonstrate that sediments in this system were acutely toxic to H. azteca, which is a resident genus. Macroinvertebrate community structure was moderately impacted downstream of the agricultural drain input. While the lowest macroinvertebrate abundances were measured at the station demonstrating the greatest water column and sediment toxicity and the highest concentrations of pesticides, macroinvertebrate metrics were more significantly correlated with bank vegetation cover than any other variable. Results of this study suggest that pesticide pollution is the likely cause of laboratory-measured toxicity in the Salinas River samples and that this factor may interact with other factors to impact the macroinvertebrate community in the system.

An evaluation of methods for calculating mean sediment quality guideline quotients as indicators of contamination and acute toxicity to amphipods by chemical mixtures.

Mean sediment quality guideline quotients (mean SQGQs) were developed to represent the presence of chemical mixtures in sediments and are derived by normalizing a suite of chemicals to their respective numerical sediment quality guidelines (SQGs). Mean SQGQs incorporate the number of SQGs exceeded and the degree to which they are exceeded and are used for comparison with observed biological effects in the laboratory or field. The current research makes it clear, however, that the number and type of SQGs used in the derivation of these mean quotients can influence the ability of mean SQGQ values to correctly predict acute toxicity to marine amphipods in laboratory toxicity tests. To determine the optimal predictive ability of mean SQGQs, a total of 18 different chemical combinations were developed and compared. The ability of each set of mean SQGQs to correctly predict the presence and absence of acute toxicity to amphipods was determined using three independent databases (n = 605, 2753, 226). Calculated mean SQGQ values for all chemical combinations ranged from 0.002 to 100. The mean SQGQ that was most predictive of acute toxicity to amphipods is calculated as SQGQ1 = ((sigma ([cadmium]/4.21 )([copper]/270)([lead]/ 12.18)([silver]/1.77)([zinc]/ 410)([total chlordane]/6)([dieldrin]/8)([total PAHoc]/1,800)([total PCB]/400))/9). Both the incidence and magnitude of acute toxicity to amphipods increased with increasing SQGQI values. To provide better comparability between regions and national surveys, SQGQ1 is recommended to serve as the standard method for combination of chemicals and respective SQGs when calculating mean SQGQs.

Statistical significance of sediment toxicity test results: threshold values derived by the detectable significance approach.

A number of methods have been employed to determine the statistical significance of sediment toxicity test results. To allow consistency among comparisons, regardless of among-replicate variability, a protocol-specific approach has been used that considers protocol performance over a large number of comparisons. Ninetieth-percentile minimum significant difference (MSD) values were calculated to determine a critical threshold for statistically significant sample toxicity. Significant toxicity threshold values (as a percentage of laboratory control values) are presented for six species and nine endpoints based on data from as many as 720 stations. These threshold values are useful for interpreting sediment toxicity data from large studies and in eliminating cases where statistical significance is assigned in individual cases because among-replicate variability is small.

A large-scale categorization of sites in San Francisco Bay, USA, based on the sediment quality triad, toxicity identification evaluations, and gradient studies.

Sediment quality was assessed in San Francisco Bay, California, USA, using a two-tiered approach in which 111 sites were initially screened for sediment toxicity. Sites exhibiting toxicity were then resampled and analyzed for chemical contamination, recurrent toxicity, and, in some cases, benthic community impacts. Resulting data were compared with newly derived threshold values for each of the metrics in a triad-based weight-of-evidence evaluation. Sediment toxicity test results were compared with tolerance limits derived from reference site data, benthic community data were compared with threshold values for a relative benthic index based on the presence and abundance of pollution-tolerant and -sensitive taxa, and concentrations of chemicals and chemical mixtures were compared with sediment quality guideline-based thresholds. A total of 57 sites exceeded threshold values for at least one metric, and each site was categorized based on triad inferences. Nine sites were found to exhibit recurrent sediment toxicity associated with elevated contaminant concentrations, conditions that met program criteria for regulatory attention. Benthic community impacts were also observed at three of these sites, providing triad evidence of pollution-induced degradation. Multi- and univariate correlations indicated that chemical mixtures, heavy metals, chlordanes, and other organic compounds were associated with measured biological impacts in the Bay. Toxicity identification evaluations indicated that metals were responsible for pore-water toxicity to sea urchin larvae at two sites. Gradient studies indicated that the toxicity tests and benthic community metrics employed in the study predictably tracked concentrations of chemical mixtures in Bay sediments.

Evaluation and use of sediment toxicity reference sites for statistical comparisons in regional assessments.

Sediment reference sites were used to establish toxicity standards against which to compare results from sites investigated in San Francisco Bay (California, USA) monitoring programs. The reference sites were selected on the basis of low concentrations of anthropogenic chemicals, distance from active contaminant sources, location in representative hydrographic areas of the Bay, and physical features characteristic of depositional areas (e.g., fine grain size and medium total organic carbon [TOC]). Five field-replicated sites in San Francisco Bay were evaluated over three seasons. Samples from each site were tested with nine toxicity test protocols and were analyzed for sediment grain size and concentrations of trace metals, trace organics, ammonia, hydrogen sulfide, and TOC. The candidate sites were found to have relatively low concentrations of measured chemicals and generally exhibited low toxicity. Toxicity data from the reference sites were then used to calculate numerical tolerance limits to be used as threshold values to determine which test sites had significantly higher toxicity than reference sites. Tolerance limits are presented for four standard test protocols, including solid-phase sediment tests with the amphipods Ampelisca abdita and Eohaustorius estuarius and sea urchin Strongylocentrotus purpuratus embryo/larval development tests in pore water and at the sediment-water interface (SWI). Tolerance limits delineating the lowest 10th percentile (0.10 quantile) of the reference site data distribution were 71% of the control response for Ampelisca, 70% for Eohaustorius, 94% for sea urchin embryos in pore water, and 87% for sea urchins embryos exposed at the SWI. The tolerance limits are discussed in terms of the critical values governing their calculation and the management implications arising from their use in determining elevated toxicity relative to reference conditions.

Sediment quality in Los Angeles Harbor, USA: a triad assessment.

Sediment quality in the Los Angeles and Long Beach Harbor area of southern California, USA, was assessed from 1992 to 1997 as part of the California State Water Resources Control Board's Bay Protection and Toxic Cleanup Program and the National Oceanic and Atmospheric Administration's National Status and Trends Program. The assessment strategy relied on application of various components of the sediment quality triad, combined with bioaccumulation measures, in a weight-of-evidence approach to sediment quality investigations. Results of bulk-phase chemical measurements, solid-phase amphipod toxicity tests, pore-water toxicity tests with invertebrate embryos, benthic community analyses (presented as a relative benthic index), and bioaccumulation measures indicated that inner harbor areas of this system are polluted by high concentrations of a mixture of sediment-associated contaminants and that this pollution is highly correlated with toxicity in laboratory experiments and degradation of benthic community structure. While 29% of sediment samples from this system were toxic to amphipods (Rhepoxynius abronius or Eohaustorius estuarius), 79% were toxic to abalone embryos (Haliotis rufescens) exposed to 100% pore-water concentrations. Statistical analyses indicated that amphipod survival in laboratory toxicity tests was significantly correlated with the number of crustacean species and the total number of species measured in the benthos at these stations. Triad measures were incorporated into a decision matrix designed to classify stations based on degree of sediment pollution, toxicity, benthic community degradation, and, where applicable, tissue concentrations in laboratory-exposed bivalves and feral fish.

Influence of sample manipulation on contaminant flux and toxicity at the sediment-water interface.

Toxicities of sediments from San Diego and San Francisco Bays were compared in laboratory experiments using sea urchin (Strongylocentrotus purpuratus) embryos exposed to pore water and at the sediment-water interface (SWI). Toxicity was consistently greater to embryos exposed at the SWI to intact (unhomogenized) sediment samples relative to homogenized samples. Measurement of selected trace metals indicated considerably greater fluxes of copper, zinc, and cadmium into overlying waters of intact sediment samples. Inhibition of sea urchin embryo development was generally greater in sediment pore waters relative to SWI exposures. Pore water toxicity may have been due to elevated unionized ammonia concentrations in some samples. The results indicate that invertebrate embryos are amenable to SWI exposures, a more ecologically relevant exposure system, and that sediment homogenization may create artifacts in laboratory toxicity experiments.

Lead poisoning in Hawaii: 1990.

Although lead (Pb) is one of the oldest known and most thoroughly described toxins, it continues to be a significant health hazard in 1990. There has been much progress in defining the nature and extent of low-level lead toxicity during the past decade. There continues to be insidious sources of lead toxicity in our environment, in water, food, paint and contaminated soil. As the epidemiology of lead poisoning is more clearly defined, toxicities are recognized as the result of lower and lower levels of exposure. Recognition of low-level lead exposure and the primary prevention of its effects on health requires a keen awareness of high-risk environments as well as the subtle symptoms and signs of lead poisoning. A high index of suspicion by primary care physicians plus government support are necessary to implement successful prevention programs.

Dorsolateral prefrontal cortex stimulation modulates electrocortical measures of visual attention: evidence from direct bilateral epidural cortical stimulation in treatment-resistant mood disorder.

Electrocortical activity is increasingly being used to study emotion regulation and the impact of cognitive control on neural response to visual stimuli. In the current study, we used direct epidural cortical stimulation (EpCS) to examine regional specificity of PFC stimulation on the parietally-maximal late positive potential (LPP), an event-related potential (ERP) biomarker of visual attention to salient stimuli. Five patients with treatment-resistant mood disorders were stereotactically implanted with stimulating paddles over frontopolar (FP) and dorsolateral (DL) prefrontal cortex bilaterally. On their first day of activation, patients underwent sham-controlled EpCS coupled with 64-channel electroencephalograph (EEG) recordings and passive viewing of aversive and neutral images. In addition to sham, patients had either FP or DL prefrontal cortex stimulated at 2 or 4 V while they viewed neutral and aversive pictures. As expected during the sham condition, LPP was larger for aversive compared to neutral stimuli (F(1,4)=232.07, P<.001). Stimulation of DL compared to FP prefrontal cortex resulted in a reduction of the LPP (F(1,4)=8.15, P=.048). These data provide additional and unique support to the role of the DL prefrontal cortex in regulating measures of neural activity that have been linked to emotional arousal and attention. Future studies with EpCS can help directly map out various prefrontal functions in treatment-resistant mood disorder.

Leptospirosis in Hawaii: shifting trends in exposure, 1907-1984.

Leptospirosis was first recognized as an occupational disease of sugar plantation workers in Hawaii in 1907. Since then, shifts have been noted in the animal transmission cycles, the occupational groups at risk, and an increasing recognition of cases associated with avocational exposure. Surveys of the small mammal populations indicate rats, mice, and mongooses are the most important vectors in Hawaii. Serologic surveys of workers in high-risk occupations show antibody prevalence rates ranging from 12 to 82 percent. The epidemiology of leptospirosis in Hawaii is described, based on 182 cases reported to the Hawaii Department of Health from 1970-1984. The most common infecting serovar was mankarso in the Icterohaemorrhagiae serogroup; other serovars in the Icterohaemorrhagiae group were also frequently implicated as causing disease. The manifestations of disease noted by physicians in Hawaii are similar to those observed in the continental U.S. Fever, myalgia, and headache were the most common symptoms reported in the majority of cases in Hawaii; jaundice was noted in the records of 24 percent. Recommendations made to interrupt the cycle of transmission and reduce the chances of exposure in occupational settings include the control of rodent populations and vaccination of domestic animals. Personal hygiene among workers is to be encouraged, and the development of prophylactic measures is suggested either by immunization or by chemoprophylaxis.

Stored blood platelets and microaggregate formation.

The structure and function of platelets in stored blood were tested for 21 days of storage with both light and electron microscopy as well as determination of platelet aggregation response to adenosine diphosphate. Observations were made for a period of 21 days of storage at 4 degrees C. These observations demonstrate the appearance of spontaneous platelet aggregates in stored blood which differ morphologically from aggregates induced by the addition of adenosine diphosphate during the first ten days of storage. The appearance of spontaneous platelet aggregates paralleled a decrease in platelet count and progressive decline in the number of morphologically normal appearing platelets. The platelets that were induced to aggregate with adenosine diphosphate formed more closely packed aggregates that those that formed spontaneously and that the adenosine diphosphate-induced aggregates could still be induced through the tenth day of storage, at which time few morphologically normal platelets could be clearly identified in the plasma. Spontaneous platelet aggregates showed no fibrin in the microaggregates but rather significant numbers of leukocytes contained in the aggregates which degenerated progressively beyond a storage period of five days.

Causes of sediment toxicity to Mytilus galloprovincialis in San Francisco Bay, California.

Since the San Francisco Regional Monitoring Program (RMP) sampling began, elutriate samples prepared with sediment from the Grizzly Bay monitoring station have been consistently toxic to bivalve larvae (Mytilus galloprovincialis). An investigation into the cause of toxicity was initiated with a Phase I Toxicity Identification Evaluation (TIE) using bivalve embryos. TIE results and chemical analyses of elutriate samples suggested that divalent metals were responsible for the observed toxicity. Following the initial characterization of trace metals as toxicants, additional TIEs were performed on elutriates prepared from three additional Grizzly Bay samples collected between 1997 and 2001. Additional TIEs included ethylenediamine tetraacetic acid (EDTA) treatments in a sediment-water interface (SWI) exposure system, and the use of a cation exchange column with serial elution of sample fractions with hydrochloric acid of increasing normality. EDTA significantly reduced toxicity in overlying water in the SWI system. The cation exchange column reduced both toxicity and concentrations of trace metals, and serial elution of the column added back both toxicity and specific metals contained in individual acid fractions. Chemical analyses of three elutriate samples demonstrated copper concentrations were within the range toxic to bivalves. Results of Phase I TIEs, additional Phase II treatments, SWI exposures, and metals analyses indicate the potential for metal toxicity in sediments from this estuarine site. When combined with the results of standard TIE methods, a solid-phase cation extraction and elution approach identified copper as the most probable cause of toxicity.

A comparison of in situ and laboratory toxicity tests with the estuarine amphipod Eohaustorius estuarius.

Amphipod survival in laboratory and in situ exposures was assessed using the eastern Pacific Haustoriid species Eohaustorius estuarius. Toxicity test results were compared using intact (unhomogenized) and homogenized sediment samples in both field and laboratory exposures. Experiments were conducted in Moss Landing Harbor, California, an impaired waterbody under 303 (d) of the US Clean Water Act. Synoptic laboratory and in situ sediment toxicity tests were conducted at two stations: Sandholdt Bridge (SB), the most contaminated station in the harbor, and at the South Jetty (SJ), a more marine station near the mouth of the harbor. We found that Eohaustorius is amenable to in situ testing. Despite highly variable field salinity regimes (6-32 PSU at SB and 21-34 PSU at SJ), in situ control survival was 87% and 84% at SB and SJ, respectively. Amphipod survival was lower in the in situ exposures relative to the laboratory exposures at both sites. Survival at SB was 30% and 76% in the homogenized in situ and laboratory samples, respectively, and 40% and 64% in the intact (unhomogenized) in situ and laboratory samples, respectively. Neither the homogenized or intact samples from the SJ station were toxic in laboratory experiments, but amphipod survival was only 40% in the intact in situ exposure at this station, possibly due to predation. These experiments suggest that the interaction of contaminants and variable physical parameters such as salinity and temperature may have resulted in lower survival in the in situ exposures. Sediment homogenization prior to in situ deployment may have reduced effects of predators in some samples.

Causes of ambient toxicity in the Calleguas Creek watershed of southern California.

A combination of toxicity tests, chemical analyses, and Toxicity Identification Evaluations (TIEs) were used to investigate receiving water toxicity in the Calleguas Creek watershed of southern California. Studies were conducted from 1995 through 1999 at various sites to investigate causes of temporal variability of toxicity throughout this system. Causes of receiving water toxicity varied by site and species tested. Investigations in the lower watershed (Revolon Slough, Santa Clara Drain, Beardsley Wash) indicated that toxicity of samples to the cladoceran Ceriodaphnia dubia was due to elevated concentrations of the organophosphate pesticide chlorpyrifos, while causes of intermittent toxicity to fathead minnows (Pimephales promelas) and the alga Selanastrum capricornutum were less clear. Investigations at sites in the middle and upper reaches of the watershed (Arroyo Simi and Conejo Creek) indicated that the pesticide diazinon was the probable cause of receiving water toxicity to Ceriodaphnia. Elevated ammonia was the cause of toxicity to fathead minnows in the upper watershed sites. Results of these and previous studies suggest that biota are impacted by degraded stream quality from a variety of point and non-point pollution sources in the Calleguas Creek watershed. Water quality resource manager's efforts to identify contaminant inputs and implement source control will be improved with the findings of this study.

Influence of salinity on copper and azide toxicity to larval topsmelt Atherinops affinis (Ayres).

Performance of a 7-d growth and survival toxicity test protocol using larval topsmelt, Atherinops affinis (Ayres), was evaluated for copper chloride and sodium azide at representative estuarine salinities. Results showed that topsmelt are amenable to toxicity testing at estuarine salinities ranging from 5 to 34/1000 since control survival was 100% in all toxicity tests. Sensitivity to both toxicants increased at lower salinities, with the LC50s for copper ranging from 205 micrograms/L at 34/1000 to 44 micrograms/L at 10/1000, and those for sodium azide ranging from 54 mg/L at 34/1000 to 7 mg/L at 5/1000. Larval tissue osmolality decreased with increasing copper concentration relative to control fish. Copper uptake was not affected by changes in salinity. This suggests that increased sensitivity to copper was due, in part, to the increasing physiological challenge of osmoregulation. It is also possible that cupric ion concentration increased at lower salinities, resulting in reduced larval survival. It is hypothesized that increased sensitivity to azide at lower salinity was due to the interaction between azide toxicity and increasing osmotic challenge. A second experiment with azide showed that larval acclimation time did not affect the interaction between salinity and azide toxicity.