Faculty Bibliography

Asbestos and benzo(a)pyrene diol epoxide (BPDE) are pulmonary carcinogens with synergistic interaction in causing lung cancer. We used Affymetrix microarrays to study gene modulation in vitro using normal human bronchial epithelial cells exposed to chrysotile asbestos and/or BPDE for 4 or 24 h. Linear models were used to compare treated cells to controls at each time point to identify statistically significant up- or downregulation of genes. Profiles of genes regulated by chrysotile were dominated by cytokines, growth factors, and DNA damage. Profiles of genes with BPDE and chrysotile regulation were correlated with proliferation, DNA damage recognition and nucleotide-excision repair, cytokines, and apoptosis. Chemokines, growth-regulated oncogene-alpha (Gro-alpha, CXCL-1), and IL-8, were significantly increased, and these had previously been observed in bronchoalveolar lavage from asbestos workers or in animal models. Interestingly, the Hermansky-Pudlak gene, which is mutated in an autosomal recessive form of pulmonary fibrosis, was downregulated threefold by BPDE at 4 h. This is an interesting example of gene (Hermansky-Pudlak syndrome) and environment (BPDE) interaction. Transcription factors, including activating transcription factor 3 and Cbp/p300-interacting transactivator, were upregulated by chrysotile. Real Time PCR for IL-8, ATF-3, GADD45B, CXC Ligand 1, and CTGF compared to GAPDH validated microarray findings at 24 h. These in vitro findings in NHBE cells model environment-gene interaction for asbestos and BPDE, highlighting effects of inflammation, fibrosis, proliferation, and DNA damage recognition and repair

Computerized drug utilization review (DUR) can potentially reduce adverse drug events. We examined automated DUR for home healthcare patients with diabetes or hypertension. Sixty-eight percent of diabetes patients and 50.7% of hypertension patients triggered severe, moderate, or duplicative alerts. Among diabetes patients, 74.3% of duplicative alerts were trivial or inappropriate, compared with 3.9% among hypertension patients. Experts judged that 40.5% of high-risk diabetes patients and 53.6% of hypertension patients had alerts requiring nurse follow-up. Adequate follow-up was significantly lower for the former. The relationship between inappropriate alerts and poorer follow-up reinforces the need for more specific alert systems to focus clinicians' attention on clinically important alerts.

Background: A serological marker for pancreatic cancer may allow for early detection and potentially more effective treatments. Pro-carboxypeptidase A (pro-CPA) is produced exclusively in the pancreas and converted to its active form, CPA, in the intestinal lumen. We hypothesized that alterations in serum pro-CPA and/or CPA may be useful as a diagnostic test for pancreatic cancer. Patients and methods: Serum samples obtained from 34 patients with pancreatic adenocarcinoma prior to surgical intervention and 64 control patients were assayed for pro-CPA and CPA. A variety of statistical methods was used to evaluate the utility of these measurements individually and in combination to classify the samples with respect to the presence or absence of pancreatic adenocarcinoma. Results: Because of positive skewing of the data in some populations, transformation of the data to natural logarithmic scales was used and resulted in normal distributions. All pancreatic cancer patients had ln(CPA) levels within or below the normal range defined as two standard deviations from the control group mean (-2.714+/-0.413). Ln(pro-CPA) levels in 24 of 34 cancer patients were outside the normal range of the control group (0.306+/-0.33). Pancreatic cancer patients with ln pro-CPA values within the control range had low ln CPA, advanced stage and/or evidence of pancreatic insufficiency. While each of these individual values (ln pro-CPA or ln CPA) does not adequately separate all control from cancer patients, a bivariate classification rule is presented that uses both ln pro-CPA and ln CPA simultaneously to predict the presence of pancreatic cancer with a sensitivity of 91% and a specificity of 95%. Conclusions: The data presented suggest that abnormalities in serum pro-CPA and CPA levels are associated with the presence of pancreatic cancer