Citations

Abstract To determine whether Colles' fracture, generally considered a manifestation of postmenopausal osteoporosis, is associated with a decrease in bone density at the site of fracture, we measured bone mineral density of the ultradistal radius (UDR-BMD) by single-photon absorptiometry with computer-assisted image processing. In 119 normal women (ages 22–92 years), UDR-BMD decreased by 17% between ages 30 and 75 years. From UDR-BMD measurements in these normal women and in 40 women (ages 53–80 years) with Colles' fracture alone, a population-based analysis was made to estimate fracture risk at different values of UDR-BMD. Colles' fracture was uncommon at UDR-BMD > 0.40 g/cm2 (the “fracture threshold”). As bone density decreased below this level, fractures became more frequent (a “gradient of risk”).

Abstract Cell-cell interactions are important in the regulation of endocrine cell secretion. To investigate the possibility that cell communication may alter the regulation of parathyroid cell secretion, we utilized the reverse hemolytic plaque assay (RHPA) to measure parathyroid hormone (PTH) release from individual cells. Bovine parathyroid cells were dispersed and plated with protein A-conjugated erythrocytes at cell densities ranging from 0.9 to 36 X 102 cells/cm2 in 0.2 mM calcium. Cell populations were greater than 98% homogeneous as determined by immunocytochemistry and in situ hybridization for PTH mRNA. Plaques were developed and data analyzed for the amount of PTH per cell released (plaque area in μm2 X 104) and the determination of cell recruitment (% plaques formed). A positive correlation existed between parathyroid cell density and the amount of PTH released. As the distance between cells increased, the plaque area (amount of PTH released per cell) decreased (ranging from 1.0 X 1044 μm2 at 0.9 X 102 cells/cm2 versus 1.6 X 104 μm2 at 36 X 102 cells/cm2). The percentage of cells releasing PTH (recruitment) also decreased (16% at 0.9 X 102 cells/cm2 versus 47% at 36 X 102 cells/cm2). These data suggest that parathyroid cells in close proximity are stimulated to secrete more hormone than those at lesser densities. In addition, parathyroid cells are recruited to secrete PTH when plated at high density. Factor(s) released by the parathyroid cell may increase cell responsiveness and stimulate secretion in a paracrine fashion.

AbstractPurpose: Over the past two decades, there has been significant interest in targeting HER-2/neu in immune-based approaches for the treatment of HER-2/neu+ cancers. For example, peptide vaccination using a CD8 T cell–activating HER-2/neu epitope (amino acids 369-377) is an approach that is being considered in advanced phase clinical trials. Studies have suggested that the persistence of HER-2/neu–specific CD8 T cells could be improved by incorporating human leukocyte antigen (HLA) class II epitopes in the vaccine. Our goal in this study was to identify broad coverage HLA-DR epitopes of HER-2/neu, an antigen that is highly expressed in a variety of carcinomas.Experimental Design: A combination of algorithms and HLA-DR–binding assays was used to identify HLA-DR epitopes of HER-2/neu antigen. Evidence of preexistent immunity in cancer patients against the identified epitopes was determined using IFN-γ enzyme-linked immunosorbent spot (ELIspot) assay.Results: Eighty-four HLA-DR epitopes of HER-2/neu were predicted, 15 of which had high binding affinity for ≥11 common HLA-DR molecules. A degenerate pool of four HLA-DR–restricted 15-amino acid epitopes (p59, p88, p422, and p885) was identified, against which >58% of breast and ovarian cancer patients had preexistent T-cell immunity. All four epitopes are naturally processed by antigen-presenting cells. Hardy-Weinberg analysis showed that the pool is useful in ∼84% of population. Lastly, in this degenerate pool, we identified a novel in vivo immunodominant HLA-DR epitope, HER-2/neu88-102 (p88).Conclusion: The broad coverage and natural immunity to this epitope pool suggests potential usefulness in HER-2/neu–targeting, immune-based therapies such as vaccines. Clin Cancer Res; 16(3); 825–34

Background The duration of time that elective noncardiac surgery (NCS) should be delayed after percutaneous coronary intervention (PCI) with bare metal stents (BMSs) is unknown. Methods This large, single-center, retrospective study examined the relation between complication rate in patients with BMSs undergoing NCS and the duration of time between PCI and NCS. Primary endpoints included in-hospital major adverse cardiac events (death, myocardial infarction, stent thrombosis, or repeat revascularization with either coronary artery bypass grafting or PCI of the target vessel) and bleeding events. The relation between the events and the timing of noncardiac surgery after PCI with BMS was assessed using univariate analysis and multiple logistic regression. Results From January 1, 1990, to January 1, 2005, a total of 899 patients were identified. The frequency of major adverse cardiac events was 10.5% when NCS was performed less than 30 days after PCI with BMS, 3.8% when NCS was performed between 31 and 90 days after PCI with BMS, and 2.8% when NCS was performed more than 90 days after PCI with BMS. In univariate and multivariate analyses, a shorter time interval between PCI with BMS and noncardiac surgery was significantly associated with increased incidence of major adverse cardiac events (univariate: P < 0.001; odds ratio = 4.0; 95% confidence interval, 2.0-8.3; multivariate: P = 0.006; odds ratio = 3.2; 95% confidence interval, 1.5-6.9). Bleeding events were not associated with time between PCI with BMS and NCS or with the use of antiplatelet therapy in the week before NCS. Conclusions The incidence of major adverse cardiac events is lowest when NCS is performed at least 90 days after PCI with BMS.

OBJECTIVE: Despite the magnitude of the problem of catheter-associated bloodstream infections (CA-BSIs) in children, relatively little research has been performed to identify effective strategies to reduce these complications. In this study, we aimed to develop and evaluate effective catheter-care practices to reduce pediatric CA-BSIs. STUDY DESIGN AND METHODS: Our study was a multi-institutional, interrupted time-series design with historical control data and was conducted in 29 PICUs across the United States. Two central venous catheter–care practice bundles comprised our intervention: the insertion bundle of pediatric-tailored care elements derived from adult efforts and the maintenance bundle derived from the Centers for Disease Control and Prevention recommendations and expert pediatric clinician consensus. The bundles were deployed with quality-improvement teaching and methods to support their adoption by teams at the participating PICUs. The main outcome measures were the rate of CA-BSIs from January 2004 to September 2007 and compliance with each element of the insertion and maintenance bundles from October 2006 to September 2007. RESULTS: Average CA-BSI rates were reduced by 43% across 29 PICUs (5.4 vs 3.1 CA-BSIs per 1000 central-line-days; P &lt; .0001). By September 2007, insertion-bundle compliance was 84% and maintenance-bundle compliance was 82%. Hierarchical regression modeling showed that the only significant predictor of an observed decrease in infection rates was the collective use of the insertion and maintenance bundles, as demonstrated by the relative rate (RR) and confidence intervals (CIs) (RR: 0.57 [95% CI: 0.45–0.74]; P &lt; .0001). We used comparable modeling to assess the relative importance of the insertion versus maintenance bundles; the results showed that the only significant predictor of an infection-rate decrease was maintenance-bundle compliance (RR: 0.41 [95% CI: 0.20–0.85]; P = .017). CONCLUSIONS: In contrast with adult ICU care, maximizing insertion-bundle compliance alone cannot help PICUs to eliminate CA-BSIs. The main drivers for additional reductions in pediatric CA-BSI rates are issues that surround daily maintenance care for central lines, as defined in our maintenance bundle. Additional research is needed to define the optimal maintenance bundle that will facilitate elimination of CA-BSIs for children.

AbstractBackground: The MTHFR C677T TT genotype is associated with a 15% to 18% reduction in colorectal cancer risk, but it is not clear if other variants of the gene are associated with colorectal cancer risk.Methods: We used a tagSNP approach to comprehensively evaluate associations between variation in the MTHFR gene and colorectal cancer risk using a large family-based case-control study of 1,750 population-based and 245 clinic-based families from the Colon Cancer Family Registry. We assessed 22 TagSNPs, selected based on pairwise r2 &gt;95%, using the Haploview Tagger and genotyped the TagSNPs on the Illumina GoldenGate or Sequenom platforms. The association between single nucleotide polymorphisms and colorectal cancer was assessed using log-additive, codominant, and recessive models.Results: From studying the population-based families, the C677T (rs1801133) and A1298C (rs1801131) polymorphisms were associated with a decreased colorectal cancer risk overall [odds ratio (OR), 0.81; 95% confidence interval (95% CI), 0.63-1.04; and OR, 0.82; 95% CI, 0.64-1.07, respectively]. The 677 TT genotype was associated with a decreased risk of microsatellite-stable/microsatellite-low tumors (OR, 0.69; 95% CI, 0.49-0.97) and an increased risk of microsatellite-high tumors (OR, 2.22; 95% CI, 0.91-5.43; Pinteraction = 0.01), as well as an increased risk of proximal cancers and a decreased risk of distal and rectal cancers (Pinteraction = 0.02). No other single nucleotide polymorphism was associated with risk overall or within subgroups.Conclusion: The 677 TT and 1298 CC genotypes may each be associated with a decrease in colorectal cancer risk. We observed little evidence of additional genetic variability in the MTHFR gene relevant to colorectal cancer risk. Cancer Epidemiol Biomarkers Prev; 19(1); 89–100