Implementation of the Henry J. Kaiser Family Foundation's Community Health Promotion Grant Program: a process evaluation

The Community Health Promotion Grants Program, sponsored by the Henry J. Kaiser Family Foundation, represents a major health initiative that established 11 community health promotion projects. Successful implementation was characterized by several critical factors: (1) intervention activities; (2) community activation; (3) success in obtaining external funding; and (4) institutionalization. Analysis of the program was based on data from several sources: program reports, key informant surveys, and a community coalition survey. Results indicate that school-based programs focusing on adolescent health problems were the most successful in reaching the populations they were targeting. The majority of the programs were able to attract external funding, thereby adding to their initial resource base. The programs were less successful in generating health promotion activities and in achieving meaningful institutionalization in their communities.     

Mass spectrometric analysis of 2-deoxyribonucleoside and 2'-deoxyribonucleotide adducts with aldehydes derived from lipid peroxidation

An important emerging issue in chemical carcinogenesis is the role that products of endogenous metabolism play in formation of covalently modified DNA. One example is the formation of alpha, beta-unsaturated aldehydes as a result of endogenous and drug-stimulated lipid peroxidation. Malondialdehyde (MDA), crotonaldehyde (CR), 2-hexenal (HX), and 4-hydroxy-2-nonenal (HNE) react covalently with 2'-deoxyguanosine (dG) and 2'-deoxyadenosine (dA) residues on DNA to form promutagenic cyclic adducts that may be important in the etiology of cancer in humans and animals. The accurate quantification of such adducts provides a powerful tool in molecular epidemiology for assessing carcinogenic risks from various lifestyle choices (e.g. diet, drug use) in humans. 32P-Postlabeling is recognized as one of the most sensitive methods available for detection of DNA adducts in human tissues, but without adequate validation such methodology can yield inaccurate quantitative measurements. We have used LC separations in conjunction with electrospray ionization MS and tandem MS (triple quadrupole and hybrid quadrupole-orthogonal acceleration time of flight analyzers) to characterize MDA-, CR-, HX- and HNE-modified dG and nucleotide (3'- and 5'-monophosphate; 3',5'-bisphosphate) adducts. These data have been used to validate 32P-postlabeling methods for quantification of low level MDA-dG adducts formed in DNA of human and animal tissues. Availability of reliable methods for quantification of endogenous DNA damage in humans and animals is essential for determining unknown etiologies of cancer and for the assessment of cancer risks in humans.     

Dendritic cell-based vaccines in the setting of peripheral blood stem cell transplantation: CD34+ cell-depleted mobilized peripheral blood can serve as a source of potent dendritic cells

We are investigating the use of tumor-pulsed dendritic cell (DC)-based vaccines in the treatment of patients with advanced cancer. In the current study, we evaluated the feasibility of obtaining both CD34+ hematopoietic stem/ progenitor cells (HSCs) and functional DCs from the same leukapheresis collection in adequate numbers for both peripheral blood stem cell transplantation (PBSCT) and immunization purposes, respectively. Leukapheresis collections of mobilized peripheral blood mononuclear cells (PBMCs) were obtained from normal donors receiving granulocyte colony-stimulating factor (G-CSF) (for allogeneic PBSCT) and from intermediate grade non-Hodgkin's lymphoma or multiple myeloma patients receiving cyclophosphamide plus G-CSF (for autologous PBSCT). High enrichment of CD34+ HSCs was obtained using an immunomagnetic bead cell separation device. After separation, the negative fraction of mobilized PBMCs from normal donors and cancer patients contained undetectable levels of CD34+ HSCs by flow cytometry. This fraction of cells was then subjected to plastic adherence, and the adherent cells were cultured for 7 days in GM-CSF (100 ng/ml) and interleukin 4 (50 ng/ml) followed by an additional 7 days in GM-CSF, interleukin 4, and tumor necrosis factor alpha (10 ng/ml) to generate DCs. Harvested DCs represented yields of 4.1+/-1.4 and 5.8+/-5.4% of the initial cells plated from the CD34+ cell-depleted mobilized PBMCs of normal donors and cancer patients, respectively, and displayed a high level expression of CD80, CD86, HLA-DR, and CD11c but not CD14. This phenotypic profile was similar to that of DCs derived from non-CD34+ cell-depleted mobilized PBMCs. DCs generated from CD34+ cell-depleted mobilized PBMCs elicited potent antitetanus as well as primary allogeneic T-cell proliferative responses in vitro, which were equivalent to DCs derived from non-CD34+ cell-depleted mobilized PBMCs. Collectively, these results demonstrate the feasibility of obtaining both DCs and CD34+ HSCs from the same leukapheresis collection from G-CSF-primed normal donors and cancer patients in sufficient numbers for the purpose of combined PBSCT and immunization strategies.     

The diagnostic and treatment characteristics of focal liver lesions using computed tomography

Under analysis is an experience with examining and treatment of 167 patients with focal lesions of the liver using computed tomography. Percutaneous transhepatic puncture and draining the hepatic abscesses and cysts under control of computed tomography is an independent method of treatment used in 53 patients. The technique of performing the puncture and drainage is described. Specific features of surgical treatment of focal lesions of the liver are described. Decompression of bile ducts in the postoperative period is shown to be necessary. A conclusion is made about high efficiency of computed tomography in diagnosis and treatment of focal lesions of the liver.     

Microscopic measurement of cellular infiltration in the rheumatoid arthritis synovial membrane: a comparison of semiquantitative and quantitative analysis

BACKGROUND: A significant proportion of burn patients with inhalation injuries incur difficulties with airway protection, dysphagia, and aspiration. In assessing the need for intubation in burn patients, the efficacy of fiberoptic laryngoscopy was compared with clinical findings and the findings of diagnostic tests, such as arterial blood gas analysis, measurement of carboxyhemoglobin levels, pulmonary function tests, and radiography of the lateral aspect of the neck. OBJECTIVE: To determine if these patients were at risk for aspiration or dysphagia, barium-enhanced fluoroscopic swallowing studies were performed. DESIGN: Prospective study. SETTINGS: Burn intensive care unit in an academic tertiary referral center. MAIN OUTCOME MEASURES: Need for endotracheal intubation and potential for aspiration. RESULTS: Six (55%) of 11 patients had clinical findings and symptoms that indicated, under traditional criteria, endotracheal intubation for airway protection. Visualization of the upper airway with fiberoptic laryngoscopy obviated the need for endotracheal intubation in all 11 patients. These patients also failed to evidence an increased risk of aspiration or other swallowing dysfunction. CONCLUSIONS: In comparison with other diagnostic criteria, fiberoptic laryngoscopy allows differentiation of those patients with inhalation injuries who, while at risk for upper airway obstruction, do not require intubation. These patients may be safely observed in a monitored setting with serial fiberoptic examinations, thus avoiding the possible complications associated with intubation of an airway with a compromised mucosalized surface. In these patients, swallowing abnormalities do not manifest.     

Trace Enrichment and HPLC Analysis of PAHs in Edible Oils and Fat Products,using Liquid Chromatography on Electron Acceptor Stationary Phases in Connection with Reverse Phase and Fluorescence Detection

The determination of PAHs in lipids is beset with many difficulties, resulting from the low level of individual PAHs (μg/kg), the complexity of extraction and clean-up procedures required to isolate the PAHs from the oil or the food components. The purpose of this report is to describe a new method for multi-PAHs determination in lipidic matrixes. The clean-up step is realized by Donor Acceptor Complex Chromatography (DACC) with a tetrachlorophthalimidopropyl (TCPI) modified silica. Neutral lipids and other minor components, especially tocopherols which can interfere with PAH, are eluted with a hexane/methyltertiobutylether mixture. Then, PAH are eluted with pure methylene chloride and analyzed by gradient reversed phase HPLC in combination with wavelength programmed fluorescence detection. This method allows an easy and fast quantitative recovery of aromatic compounds.     

Thymidylate synthase is localized to the nuclear periphery in the yeast Saccharomyces cerevisiae

To date, the organization of DNA precursor synthesis within eukaryotic cells remains unresolved. Previous studies have suggested the existence of a multienzyme complex that is responsible for DNA precursor synthesis and is associated with sites of replication within the nucleus. Contrasting this, other studies have proposed that DNA precursor synthesis occurs outside the nucleus. To further these studies, we have addressed the location where thymidylate synthase resides in yeast. Subcellular fractionation experiments indicate thymidylate synthase is associated with purified nuclei. Consistent with this, immunofluorescence analysis suggests that thymidylate synthase is situated at the nuclear periphery.     

Congenital erythrocytosis with elevated erythropoietin level: an incorrectly set "erythrostat"?

It is well documented that IL-6 plays a critical role in B cell terminal differentiation, and in mucosal sites it stimulates proliferation and large-scale secretion of immunoglobulin by B cells, especially those committed to IgA production. The close juxtaposition of IL-6 mRNA+ cells to plasma cells in the intestinal lamina propria supports the proposition that IL-6 production in situ is an important factor determining the outcome of antibody responses at that site. However, it has not been established previously whether exogenous IL-6 could boost antibody responses in the intestine if administered with a challenge antigen. Using a resected gut loop (Thiry-Vella loop) model, we have been able to demonstrate that in mice with double loops, antibody containing cell responses to lumenal administration of ovalbumin were 50% greater in loops given intralumenal recombinant IL-6 with the challenge antigen, than in loops challenged with antigen alone. This demonstrates the efficacy of IL-6 in promoting accumulation of antibody secreting cells in the gut, and suggests a potential therapeutic role for IL-6 to enhance responses to mucosal vaccines.