Implementing the National Local Public Health System Performance Assessment: evaluation of a readiness process in Kentucky.

The objectives of the study described in this article were to test training and resource materials for preparing Kentucky public health agency staff to lead the National Local Public Health System Performance Assessment and to identify barriers encountered in implementation. Readiness supports provided to five Kentucky district and county health departments that led the system assessment process in 12 counties were evaluated using training pre- and posttests, performance assessment posttests, observations, and interviews. The training and materials provided in this study appeared to be the minimum needed for these Kentucky health departments. Training sequences need to allow time for independent study of assessment processes, and training in using and interpreting the assessment instrument should be included. Partner orientation materials targeted for nonpublic health partners would be useful. In Kentucky, barriers to completing the assessment included questions about its purpose and benefits and the lack of a self-identified local public health system. Formal training of health department staff, committed leadership, and adequate personnel resources can help overcome these barriers. The health departments that brought together system partners for the performance assessment considered it a valuable community-building educational event.     

The effects of cyclophosphamide on neurotransmission in the urinary bladder of Suncus murinus, the house musk shrew

This study has shown that cyclophosphamide treatment of the insectivore Suncus murinus, causes a down regulation in both muscarinic and P2X receptors, together with a reduced responsiveness to exogenous histamine (0.3 mM) in the urinary bladder. Electrical field stimulation (70 V, 0.3 ms, 0.5-16 Hz, 10 s every 5 min) of bladders from both control and cyclophosphamide-treated animals showed identical responses. Since post-junctional alterations have been revealed by the reduced responsiveness to exogenous carbachol (0.1 microM-3 mM) and beta,gamma-methylene ATP (0.3-300 microM), it would appear that in the bladders of cyclophosphamide-treated animals there is also a pre-junctional effect, increased transmitter release compensating for the down regulation of the receptors. As the pattern of neurotransmission of the bladder of suncus more closely resembles that of human detrusor than other commonly studied laboratory animals, this insectivore appears to be a useful animal model for the study of bladder neurotransmission in pathophysiological conditions.     

Disposition of intravenously administered pharmacologic doses of vitamin E in newborn rabbits

Newborn rabbits were given a single intravenous dose (100 mg/kg) of either alpha-tocopherol or alpha-tocopheryl acetate to compare disposition characteristics of these two forms of vitamin E. The resulting tissue concentrations of alpha-tocopherol and alpha-tocopheryl acetate differed significantly. Tissue concentrations of either form of vitamin E were much higher than those provided by normal nutrition, and remained unchanged (except in the liver) for 6 days after dose. alpha-Tocopheryl acetate was not completely converted to alpha-tocopherol, and only 50% of the dose was recovered 3 days after administration. The entire dose of alpha-tocopherol was recovered intact 3 days after administration. The persistence of very high tissue vitamin E concentrations after a single intravenous dosing, the disappearance from the body of half of the administered dose of alpha-tocopheryl acetate, and the lack of complete conversion of alpha-tocopheryl acetate to alpha-tocopherol when given intravenously have profound implications regarding the current clinical practice of giving repeated pharmacologic doses of vitamin E to newborn infants.     

Restoration of E-cadherin/beta-catenin expression in pancreatic cancer cells inhibits growth by induction of apoptosis

BACKGROUND: beta-Catenin is a component of the E-cadherin/catenin adhesion complex that maintains epithelial cell integrity. We have previously observed decreased beta-catenin expression in both human pancreatic cancer cell lines and primary tumors. To determine the significance of this finding with respect to pancreatic carcinogenesis, this study evaluated the effects of restoring expression of beta-catenin with and without E-cadherin in pancreatic cancer cells. METHODS: MiaPaca-2 cells were stably transfected with full-length cDNAs for beta-catenin, E-cadherin, or a mutated E-cadherin lacking the beta-catenin-binding domain. Doubly transfected cell clones containing beta-catenin and either E-cadherin or deleted E-cadherin were also selected. Assays for cell adhesion, cell cycle profile, motility, and apoptosis were performed. RESULTS: Cell clones expressing beta-catenin alone or beta-catenin and deleted E-cadherin did not differ significantly from the parental cell lines in any of the assays performed. In contrast, MiaPaca-2 cell clones expressing both beta-catenin and E-cadherin showed tight adhesion, decreased cell growth, and a significantly increased apoptotic index as compared to the parental line or singly transfected clones. CONCLUSIONS: MiaPaca-2 cells undergo apoptosis at a significantly increased rate after restoration of the E-cadherin/beta-catenin adhesion complex. This increase in apoptosis is dependent on the ability of E-cadherin to bind beta-catenin. Loss of beta-catenin expression may therefore provide pancreatic cancer cells with a growth advantage that contributes to tumor progression.     

MR imaging of human brain at 3.0 T: preliminary report on transverse relaxation rates and relation to estimated iron content

PURPOSE: To determine the transverse relaxation rates R2 and R2' from several gray matter regions and from frontal cortical white matter in healthy human brains in vivo and to determine the relationship between relaxation rates and iron concentration [Fe]. MATERIALS AND METHODS: Six healthy adults aged 19-42 years underwent thin-section gradient-echo sampling of free induction decay and echo magnetic resonance (MR) imaging at 3.0 T. Imaging covered the mesencephalon and basal ganglia. RESULTS: Relaxation rates (mean +/- SD) were highest in globus pallidus (R2 = 25.8 seconds-1 +/- 1.1, R2' = 12.0 seconds-1 +/- 2.1) and lowest in prefrontal cortex (R2 = 14.4 seconds-1 +/- 1.8, R2' = 3.4 seconds-1 +/- 1.1). Frontal white matter measurements were as follows: R2 = 18.0 seconds-1 +/- 1.2 and R2' = 3.9 seconds-1 +/- 1.2. For gray matter, both R2 and R2' showed a strong correlation (r = 0.92, P < .001 and r = 0.90, P < .001, respectively) with [Fe]. Although the slopes of the regression lines for R2' versus [Fe] and for R2 versus [Fe] were similar, the iron-independent component of R2' (2.2 seconds-1 +/- 0.6), the value when [Fe] = 0, was much less than that of R2 (12.7 seconds-1 +/- 0.7). CONCLUSION: The small iron-independent component R2', as compared with that of R2, is consistent with the hypothesis that R2' has higher iron-related specificity.