Distribution of Epi Info software: An evaluation using the internet

INTRODUCTION: Epi Info and Epi Map are computer programs for word processing, database management, epidemiologic statistics, and mapping designed for public health professionals. The programs are in the public domain, and distribution outside the Centers for Disease Control and Prevention (CDC) has been through a variety of informal channels. METHOD: Individuals and organizations known to have distributed Epi Info or Epi Map since 1987 provided information. Distributors included CDC, the World Health Organization (WHO), commercial vendors, translators, instructors in university and public health settings, and other public health professionals. Reports documented a minimum number of 145,320 copies distributed. CONCLUSIONS: Since 1994, the Internet has become a major means of propagation, accounting for 66% of the copies for which the method of distribution was known. The Internet also was a major information source for this study.     

Targeting breast stem cells with the cancer preventive compounds curcumin and piperine

The cancer stem cell hypothesis asserts that malignancies arise in tissue stem and/or progenitor cells through the dysregulation or acquisition of self-renewal. In order to determine whether the dietary polyphenols, curcumin, and piperine are able to modulate the self-renewal of normal and malignant breast stem cells, we examined the effects of these compounds on mammosphere formation, expression of the breast stem cell marker aldehyde dehydrogenase (ALDH), and Wnt signaling. Mammosphere formation assays were performed after curcumin, piperine, and control treatment in unsorted normal breast epithelial cells and normal stem and early progenitor cells, selected by ALDH positivity. Wnt signaling was examined using a Topflash assay. Both curcumin and piperine inhibited mammosphere formation, serial passaging, and percent of ALDH+ cells by 50% at 5 μM and completely at 10 μM concentration in normal and malignant breast cells. There was no effect on cellular differentiation. Wnt signaling was inhibited by both curcumin and piperine by 50% at 5 μM and completely at 10 μM. Curcumin and piperine separately, and in combination, inhibit breast stem cell self-renewal but do not cause toxicity to differentiated cells. These compounds could be potential cancer preventive agents. Mammosphere formation assays may be a quantifiable biomarker to assess cancer preventive agent efficacy and Wnt signaling assessment can be a mechanistic biomarker for use in human clinical trials.     

Informed consent for biorepositories: assessing prospective participants' understanding and opinions

PURPOSE: Obtaining informed consent for the collection, storage, and future research use of biospecimens is challenging, as potentially complex and controversial information must be communicated clearly. We gathered input on a consent template developed for the Duke Biorepository from individuals representative of those who might one day consider contributing specimens. METHODS: Forty subjects were recruited from the Durham, NC area and screened to achieve diversity by race/ethnicity, education, age, and sex. Cognitive interviews assessed participants' (a) understanding of information in the template, and (b) opinions about that information. Participants also completed a survey assessing trust in medical researchers. RESULTS: Interviewees seemed to understand the template. Although responses were diverse, majority views emerged: more than half were comfortable with indefinite biospecimen storage, periodic contact to update information and to inform participants of additional research opportunities, the prospect that commercial products could be developed, and the fact that profits would not be shared. More than half were willing to provide medical record access, although this was a primary concern for others. More than two thirds were comfortable with not receiving individual research results as a matter of routine, but many thought they should be informed of findings with serious health implications. Lack of trust in researchers was associated with declining certain consent options. CONCLUSIONS: Protecting and promoting trust in research is essential to fostering widespread participation in biorepositories. Biorepositories should also devise ways to communicate clearly about the research being conducted and what is being learned.     

Improved work-up procedure for the production of [F]flumazenil and first results of its use with a high-resolution research tomograph in human stroke

IntroductionThe central benzodiazepine receptor (cBZR)–gamma-aminobutyric acid (GABA_A) receptor complex in the human brain plays an important role in many neurological and psychiatric disorders. ¹⁸F-Labeled flumazenil ([¹⁸F]FZ) provides a potentially useful tracer to investigate those disorders by means of positron emission tomography (PET).Methods[¹⁸F]Flumazenil was synthesized from its nitro-precursor Ro 15-2344 in DMF at high temperatures between 150°C and 160°C. Other solvents like acetonitrile and dimethylsulfoxide were also investigated as reaction media. A new HPLC method for the final purification of [¹⁸F]FZ was developed to circumvent some difficulties associated with a previously published procedure sometimes led to a contamination of [¹⁸F]FZ with Ro 15-2344. The final purification of the radiotracer was achieved using a Waters Symmetry Prep C18 HPLC column with elution with 0.05 M sodium acetate (NaOAc) buffer (pH 5)/THF/MeOH (80:10:10).Results[¹⁸F]FZ could be synthesized in reproducible radiochemical yields (RCYs) of 15–20% (decay corrected to EOB) after 80 min overall synthesis time. The synthesized [¹⁸F]FZ was applied for the first time in a human PET study in a patient with ischemic right middle cerebral artery stroke using the HRRT high-resolution research scanner (Siemens Medical Solution, Knoxville, TN, USA).Conclusions[¹⁸F]FZ is a potentially useful GABA receptor-binding PET ligand. A modified procedure for its preparation in reproducibly high radiochemical yields has been described and the [¹⁸F]FZ thus produced has been used successfully in a pilot clinical study.