Does proximity to clinic affect immunization rates and blood pressure?

OBJECTIVE: Primary care clinics are frequently placed in neighborhoods to improve access. Little is known whether or not this improves outcomes. We sought to determine if childhood immunization rates and adult blood pressure (BP) levels are related to proximity of home to clinic. METHOD: We conducted a retrospective chart review in a community family medicine clinic in a neighborhood grocery store (CC) and a hospital-based family medicine residency clinic (HC) in Milwaukee, Wisconsin. Randomly selected subjects included children aged 2-5 years (n = 151 CC; 241 HC) and adult continuity patients (n = 197 CC; 242 HC). ARC-GIS was used to geocode patient home addresses, and distances were analyzed using Kruskal-Wallis, Spearman's rank correlation, or Mann-Whitney test. Proportion of primary immunization by age 2 and age at completion, numerical BP, and proportion abnormal BP were each correlated to distance and driving distance to clinic. RESULTS: Median driving distance of patient to clinic was significantly less for CC than HC (children = 1.47 versus 2.35 miles, p < 0.0001; adults = 1.53 versus 3.12, p < 0.001). For each clinic, and for all subjects combined, and for subsets by gender, ethnicity and insurance status, there was no significant correlation between proportion immunized by age 2 or age at completion and linear or categorical driving distance (or linear distance) to clinic (p = 0.12-0.99), or between BP values or proportion abnormal and distances to clinic (p = 0.44-0.97). CONCLUSIONS: In this urban area, proximity of home to clinic did not correlate with primary immunization completion or blood pressure in either a hospital-based or a community clinic.

Age-related trends in gene expression in the chemosensory-nasal mucosae of senescence-accelerated mice.

We have utilized high-density GeneChip oligonucleotide arrays to investigate the use of the senescence-accelerated mouse (SAM) as a biogerontological resource to identify patterns of gene expression in the chemosensory-nasal mucosa. Gene profiling in chronologically young and old mice of the senescence-resistant (SAMR) and senescence-prone (SAMP) strains revealed 133 known genes that were modulated by a three-fold or greater change either in one strain or the other or in both strains during aging. We also identified known genes in our study which based on their encoded proteins were identified as aging-related genes in the aging neocortex and cerebellum of mice as reported by Lee et al. (2000) [Nat. Genet. 25 (2000) 294]. Changes in gene profiles for chemosensory-related genes including olfactory and vomeronasal receptors, sensory transduction-associated proteins, and odor and pheromone transport molecules in the young SAMR and SAMP were compared with age-matched C57BL/6J mice. An analysis of known gene expression profiles suggests that changes in the expression of immune factor genes and genes associated with cell cycle progression and cell death were particularly prominent in the old SAM strains. A preliminary cellular validation study supported the dysregulation of cell cycle-related genes in the old SAM strains. The results of our initial study indicated that the use of the SAM models of aging could provide substantive information leading to a more fundamental understanding of the aging process in the chemosensory-nasal mucosa at the genomic, molecular, and cellular levels.

Chemokine regulation of macrophage recruitment into the olfactory epithelium following target ablation: involvement of macrophage inflammatory protein-1alpha and monocyte chemoattractant protein-1.

Target ablation by olfactory bulbectomy synchronizes the degenerative cell death of olfactory receptor neurons (ORNs), infiltration of macrophages, and proliferation of progenitor cells, leading to neurogenesis, ORN replacement, and regeneration of the sensory epithelium. Although macrophages participate in the degenerative and regenerative events, little is known of the molecular and cellular mechanisms associated with their recruitment during the earliest period following target ablation. Macrophage inflammatory protein-1alpha (MIP-1alpha) and monocyte chemoattractant protein-1 (MCP-1), which are members of the CC or beta-chemokine subfamily, are chemoattractants for monocytes/macrophages. Shortly after target ablation, the protein and mRNA levels for MIP-1alpha and MCP-1 were up-regulated, showing peak expression levels from 16 hr to 3 days post-OBX; this coincided with the pattern of infiltration of activated F4/80(+) macrophages. The mRNAs for MIP-1alpha and MCP-1, as well as their cognate receptors CCR1 and CCR2, respectively, were localized in resident and infiltrating macrophages in numbers commensurate with those of F4/80-immunopositive macrophages in adjacent tissue sections. The mRNA(+) macrophages were localized within olfactory epithelial compartments that corresponded with their proposed functions associated with phagocytosis, proliferation, and infiltration. Our data support the hypothesis that MIP-1alpha and MCP-1 are chemoattractant chemokines associated with the recruitment of macrophages into the olfactory epithelium shortly after target ablation.

Leukemia inhibitory factor mRNA expression is upregulated in macrophages and olfactory receptor neurons after target ablation.

After target ablation by olfactory bulbectomy (OBX), the murine olfactory epithelium (OE) undergoes degenerative changes leading to apoptosis of olfactory receptor neurons (ORNs) followed by regenerative changes that include proliferation of progenitor cells leading to neurogenesis and ORN replacement. Macrophages recruited to the OE after OBX are involved in both the degenerative and regenerative processes. Relative quantitative RT-PCR was used to demonstrate that within hours of OBX, mRNAs encoding three key components in the leukemia inhibitory factor (LIF) signaling pathway, including LIF, LIF receptor (LIFR), and STAT3, as well as cyclin D1, a growth factor sensor indicative of progenitor cell transformation, were upregulated. These mRNAs reached peak levels of expression on or before day 3 post-OBX, coincident with the peak time for macrophage recruitment and progenitor cell proliferation. Cells expressing LIF mRNA in the OE of mice at 3 days post-OBX, the time point at which LIF mRNA expression peaked, were identified using non-isotopic in situ hybridization. LIF mRNA was localized in infiltrating macrophages; near-adjacent sections exhibited macrophages immunoreactive for F4/80, a marker for activated macrophages, in numbers commensurate with those expressing LIF mRNA. LIF mRNA was also localized in surviving ORNs, identified by their expression of olfactory marker protein (OMP) mRNA and protein in near-adjacent sections. Our data suggest that LIF functions as a mitogen originating from recruited macrophages through an intercellular signaling pathway that stimulates proliferation of progenitor cells leading to neurogenesis and regeneration, and as an intracellular survival factor for traumatized ORNs.