Regional Differences and Tribal Use of American Indian/Alaska Native Cancer Data in the Pacific Northwest

In the Pacific Northwest, cancer is a leading cause of morbidity and mortality for American Indians and Alaska Natives (AI/AN). Misclassification of AI/AN race in state cancer registries causes cancer burden to be underestimated. Furthermore, local-level data are rarely available to individual tribes for use in health assessment and program planning. We corrected race coding in the cancer registries of Idaho, Oregon, and Washington using probabilistic record linkage to a file derived from patient registration records from Indian Health Service and a large urban clinic. We calculated cancer incidence and mortality measures by state, comparing AI/AN to non-Hispanic White (NHW) race. Record linkages identified a high prevalence of misclassified race. Differences in AI/AN cancer patterns were identified across the three state region. Compared to NHW, AI/AN experienced disproportionate late stage rates of some screen-detectable cancers. The correct classification of race is a crucial factor in cancer surveillance and can reveal regional differences even within a relatively small area. The availability of local-level cancer data can help inform tribes in appropriate intervention efforts.     

Contributions of the N- and C-terminal domains of IGF binding protein-6 to IGF binding

Insulin-like growth factors IGF-I and IGF -II are important mediators of growth. A family of six high affinity IGF binding proteins (IGFBPs) modulate IGF action. IGFBPs have three domains, of which the N- and C-domains are involved in high affinity IGF binding. IGFBP-6 is unique in its 20-100-fold IGF-II binding specificity over IGF-I. The aim of this study was to determine the contributions of the N- and C-domains of IGFBP-6 to its IGF binding properties. We confirmed that differential dissociation kinetics are responsible for the IGF-II binding preference of IGFBP-6. The N-domain has rapid association kinetics, similar to full-length IGFBP-6, but both IGF-I and -II dissociate rapidly from this domain, thereby reducing its binding affinity for IGF-II approximately 50-fold. However, the N-domain binds IGF-I and -II with similar affinities and it has a similar IGF-I binding affinity to full-length IGFBP-6. This suggests that the C-domain confers the IGF-II binding preference of IGFBP-6; indeed, IGF-I bound inconsistently with very low affinity to the C-domain. Coincubation studies showed that isolated N- and C-domains of IGFBP-6 do not strongly cooperate to enhance IGF binding. The results of the binding studies are supported by the effects of the IGFBP-6 domains on IGF-induced colon cancer cell proliferation; the N-domain inhibited IGF-II induced proliferation with approximately 20-fold lower potency than IGFBP-6 and it was equipotent in inhibiting IGF-I- and IGF-II-induced proliferation. Coincubation of C-domain had no additional effect on N-domain-induced inhibition of proliferation. In conclusion, both the N- and C-domains of IGFBP-6 are involved in IGF binding, the C-domain is responsible for the IGF-II binding preference of IGFBP-6 and intact IGFBP-6 is necessary for high affinity IGF binding.     

Impact of Empiric Antimicrobial Therapy on Outcomes in Patients with <Emphasis Type="Italic">Escherichia coli</Emphasis> and <Emphasis Type="Italic">Klebsiella pneumoniae</Emphasis> Bacteremia: A Cohort Study

Background  

It is unclear whether appropriate empiric antimicrobial therapy improves outcomes in patients with bacteremia due to Escherichia coli or Klebsiella. The objective of this study is to assess the impact of appropriate empiric antimicrobial therapy on in-hospital mortality and post-infection length of stay in patients with Escherichia coli or Klebsiella bacteremia while adjusting for important confounding variables.