Hematopoietic growth factors for graft failure after bone marrow transplantation: a randomized trial of granulocyte-macrophage colony- stimulating factor (GM-CSF) versus sequential GM-CSF plus granulocyte- CSF

Delay in hematologic recovery after bone marrow transplantation (BMT) can extend and amplify the risks of infection and hemorrhage, compromise patients' survival, and increase the duration and cost of hospitalization. Because current studies suggest that granulocyte- macrophage (GM) colony-stimulating factor (CSF) may potentiate the sensitivity of hematopoietic progenitor cells to G-CSF, we performed a prospective, randomized trial comparing GM-CSF (250 micrograms/m2/d x 14 days) versus sequential GM-CSF x 7 days followed by G-CSF (5 micrograms/kg/d x 7 days) as treatment for primary or secondary graft failure after BMT. Eligibility criteria included failure to achieve a white blood cell (WBC) count > or = 100/microL by day +21 or > or = 300/microL by day +28, no absolute neutrophil count (ANC) > or = 200/microL by day +28, or secondary sustained neutropenia after initial engraftment. Forty-seven patients were enrolled: 23 received GM-CSF (10 unrelated, 8 related allogeneic, and 5 autologous), and 24 received GM- CSF followed by G-CSF (12 unrelated, 7 related allogeneic, and 5 autologous). For patients receiving GM-CSF alone, neutrophil recovery (ANC > or = 500/microL) occurred between 2 and 61 days (median, 8 days) after therapy, while those receiving GM-CSF+G-CSF recovered at a similar rate of 1 to 36 days (median, 6 days; P = .39). Recovery to red blood cell (RBC) transfusion independence was slow, occurring 6 to 250 days (median, 35 days) after enrollment with no significant difference between the two treatment groups (GM-CSF: median, 30 days; GM-CSF+G- CSF; median, 42 days; P = .24). Similarly, platelet transfusion independence was delayed until 4 to 249 days (median, 32 days) after enrollment, with no difference between the two treatment groups (GM- CSF: median, 28 days; GM-CSF+G-CSF: median, 42 days; P = .38). Recovery times were not different between patients with unrelated donors and those with related donors or autologous transplant recipients. Survival at 100 days after enrollment was superior after treatment with GM-CSF alone. Only 1 of 23 patients treated with GM-CSF died versus 7 of 24 treated with GM-CSF+G-CSF who died 16 to 84 days (median, 38 days) after enrollment, yielding Kaplan-Meier 100-day survival estimates of 96% +/- 8% for GM-CSF versus 71% +/- 18% for GM-CSF+G-CSF (P = .026). These data suggest that sequential growth factor therapy with GM-CSF followed by G-CSF offers no advantage over GM-CSF alone in accelerating trilineage hematopoiesis or preventing lethal complications in patients with poor graft function after BMT.(ABSTRACT TRUNCATED AT 400 WORDS)     

Arsenic exposure in drinking water: an unrecognized health threat in Peru

ObjectiveTo assess the extent of arsenic contamination of groundwater and surface water in Peru and, to evaluate the accuracy of the Arsenic Econo-Quick^™ (EQ) kit for measuring water arsenic concentrations in the field.MethodsWater samples were collected from 151 water sources in 12 districts of Peru, and arsenic concentrations were measured in the laboratory using inductively-coupled plasma mass spectrometry. The EQ field kit was validated by comparing a subset of 139 water samples analysed by laboratory measurements and the EQ kit.FindingsIn 86% (96/111) of the groundwater samples, arsenic exceeded the 10 µg/l arsenic concentration guideline given by the World Health Organization (WHO) for drinking water. In 56% (62/111) of the samples, it exceeded the Bangladeshi threshold of 50 µg/l; the mean concentration being 54.5 µg/l (range: 0.1–93.1). In the Juliaca and Caracoto districts, in 96% (27/28) of groundwater samples arsenic was above the WHO guideline; and in water samples collected from the section of the Rímac river running through Lima, all had arsenic concentrations exceeding the WHO limit. When validated against laboratory values, the EQ kit correctly identified arsenic contamination relative to the guideline in 95% (106/111) of groundwater and in 68% (19/28) of surface water samples.ConclusionIn several districts of Peru, drinking water shows widespread arsenic contamination, exceeding the WHO arsenic guideline. This poses a public health threat requiring further investigation and action. For groundwater samples, the EQ kit performed well relative to the WHO arsenic limit and therefore could provide a vital tool for water arsenic surveillance.     

Long-Term Consequences of Adolescent Gang Membership for Adult Functioning

Objectives. We examined the possible public health consequences of adolescent gang membership for adult functioning.Methods. Data were drawn from the Seattle Social Development Project, a longitudinal study focusing on the development of positive and problem outcomes. Using propensity score matching and logistic regression analyses, we assessed the effects of adolescent gang membership on illegal behavior, educational and occupational attainment, and physical and mental health at the ages of 27, 30, and 33 years.Results. In comparison with their nongang peers, who had been matched on 23 confounding risk variables known to be related to selection into gang membership, those who had joined a gang in adolescence had poorer outcomes in multiple areas of adult functioning, including higher rates of self-reported crime, receipt of illegal income, incarceration, drug abuse or dependence, poor general health, and welfare receipt and lower rates of high school graduation.Conclusions. The finding that adolescent gang membership has significant consequences in adulthood beyond criminal behavior indicates the public health importance of the development of effective gang prevention programs.Research has consistently shown that gang membership has proximal adverse consequences during adolescence that, in turn, lead to significant social and economic costs.1–3 Active gang members are much more likely than their nongang peers to engage in criminal behavior,2,4,5 especially serious and violent offending6; in addition, they are more likely to be involved in drug use and selling,5 have more difficulties in school,4 and are more likely to be violently victimized.3 However, with few exceptions, there is scant research on possible broader, long-term public health consequences of gang membership.7–9Levitt and Vankatesh,8 in a 10-year follow-up of a sample of Chicago youths, found that those who reported being in a gang during adolescence were more likely to be arrested and incarcerated as adults, were more likely to rely on illegal income, and had obtained less formal education than their nongang peers. When they controlled for background characteristics such as home environment and early school performance, only the relationship between adolescent gang membership and illegal income in adulthood remained significant.In an ethnographic study, Hagedorn10 conducted follow-up interviews of 228 Milwaukee-based founding male gang members several years after his initial study. Two thirds of the sample did not have a high school diploma or general equivalency diploma (GED), fewer than 32% were employed, and more than 63% had been incarcerated.In a quantitative study involving a community sample, Thornberry et al.9 examined the extent to which gang membership negatively affected the timeliness of developmental transitions into adulthood, such as completion of schooling and establishment of a career. They found that, after control for individual and environmental risks, male respondents who had been short-term or long-term gang members in adolescence had a greater likelihood of cohabitation before marriage at the age of 22 years than male respondents who had not been gang members. Long-term gang members also had significantly higher rates of unstable employment, school dropout, early pregnancy, and teenage parenthood at the follow-up. Female gang members were more likely to experience untimely or problematic transitions, including unstable employment, teenage pregnancy, and early motherhood. Both male and female former gang members were more likely to report adult arrests.Recently, Krohn et al.11 found that there was an indirect positive relationship between adolescent gang membership and engagement in street crime and arrest in adulthood. Specifically, gang membership was related to precocious transitions into adulthood that then predicted disrupted family relationships and economic instability. They found that this path eventually led to criminal behaviors at the age of 30 years. In our study, we extended these investigations by assessing the effects of gang membership on adult functioning holistically, examining possible later adult outcomes.Life course theory12–14 provides a framework to understand how gang membership in adolescence may affect illegal behavior, educational and occupational attainment, and physical and mental health in adulthood. This theory emphasizes the strong connection between childhood events and experiences in adulthood (trajectories), as well as significant events that create a disruption in a trajectory (turning points). Although we did not directly test a trajectory change model in this study, life course theory would suggest that joining a gang during adolescence may initiate a negative developmental cascade into both criminal and noncriminal domains, including decreased educational and occupational attainment and poor physical and mental health.15,16 Indeed, Melde and Esbensen reported that “youth who join gangs experience noteworthy changes in their emotions, attitudes, and behavior,”17^(p539) suggesting that gang membership may serve as a significant turning point in an individual’s life course.One such life course theory, the social development model,18 provides specific mechanisms through which these consequences may operate. This model articulates the mechanisms of socialization and identifies parallel but separate causal paths for prosocial and antisocial processes consisting of opportunities for involvement, actual involvement, skills, rewards, bonding, and adoption of beliefs. Participation in the prosocial path is seen to increase subsequent positive outcomes and decrease risk behaviors. By contrast, participation in the antisocial path is seen to decrease positive outcomes and increase problem behaviors. From the perspective of this model, gang membership in adolescence may serve as a turning point, drastically changing the opportunity structure for young people. As gang-involved youths move through subsequent cycles of socialization, they are likely to experience reduced prosocial functioning across several domains and escalated problem behaviors as they transition into adulthood, even if they are no longer members of a gang.According to Krohn and Thornberry,

it is reasonable to expect that being a member of a gang during adolescence will be associated with disrupted transitions from adolescence to adulthood and, ultimately, will adversely impact life chances.7^(p149)

They noted that the challenge is to discover empirically to what extent gang membership contributes to negative outcomes in adulthood over and above general delinquency and other risk factors in adolescence. This was precisely the aim of our study.     

A signal generator for testing extracellular recording amplifiers and probes

A portable signal generator that simulates the amplitude and frequency of neuronal signals for testing extracellular recording amplifiers is described. The signal generator is easy to construct and it is extremely useful in tracing signal processing stages in neurophysiological equipment.