Resource utilization related to atrial fibrillation after coronary artery bypass grafting.

BACKGROUND: Studies of resource utilization by patients with new-onset atrialfibrillation after coronary artery bypass grafting have addressed only length of stay and bed charges. OBJECTIVE: To compare resource utilization between patients with new-onset atrial fibrillation and patients without atrialfibrillation after isolated coronary artery bypass grafting. METHODS: Retrospective review of clinical and administrative electronic databases for 720 subjects who underwent isolated coronary artery bypass grafting with cardiopulmonary bypass in 25 months at one medical center The prevalence of atrial fibrillation was determined, and resource utilization in various hospital cost centers was compared between subjects with and without atrialfibrillation. RESULTS: The prevalence of new-onset atrial fibrillation was 33.1%. Compared with subjects without atrialfibrillation, subjects with atrialfibrillation had a longer stay (5.8 +/- 2.4 vs. 4.4+/-1.2 days, P<.001), more days receiving mechanical ventilation (P =.002) and oxygen therapy (P<.001), and higher rates of readmission to the intensive care unit (4.6% vs. 0.2%, P<.001). Subjects with atrial fibrillation also had more laboratory tests (P<.001) and more days receiving cardiac drugs, heparin, diuretics, and electrolytes. Subjects with atrialfibrillation had higher total postoperative charges ($57261 +/- $17101 vs. $50905 +/- $10062, P = .001), a mean difference of $6356. The mean differences were greatest for bed charges ($1642), laboratory charges ($1215), pharmacy ($989), and respiratory care ($582). CONCLUSION: The economic impact of atrialfibrillation after coronary artery bypass grafting has been underestimated.     

Brief Report: Incidence of Selected Opportunistic Infections Among Children With Juvenile Idiopathic Arthritis

Objective

To compare incidence rates of selected opportunistic infections among children with and children without juvenile idiopathic arthritis (JIA).

Methods

Using US national Medicaid administrative claims data from 2000 through 2005, we identified a cohort of children with JIA based on physician diagnosis codes and dispensed medications. We also identified a non‐JIA comparator cohort of children diagnosed as having attention deficit hyperactivity disorder (ADHD). We defined 15 types of opportunistic infection using physician diagnosis or hospital discharge codes; criteria for 7 of these types also included evidence of treatment with specific antimicrobial agents. We calculated infection incidence rates. The rates in the ADHD comparator cohort were standardized to the age, sex, and race distribution of the JIA cohort. We calculated incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs) to compare infection rates.

Results

The JIA cohort included 8,503 children with 13,990 person‐years of followup. The ADHD comparator cohort included 360,362 children with 477,050 person‐years of followup. When all opportunistic infections were considered together as a single outcome, there were 42 infections in the JIA cohort (incidence rate 300 per 100,000 person‐years; IRR 2.4 [95% CI 1.7–3.3] versus ADHD). The most common opportunistic infections among children with JIA were 3 cases of Coccidioides (incidence rate 21 per 100,000 person‐years; IRR 101 [95% CI 8.1–5,319] versus ADHD), 5 cases of Salmonella (incidence rate 35 per 100,000 person‐years; IRR 3.8 [95% CI 1.2–9.5]), and 32 cases of herpes zoster (incidence rate 225 per 100,000 person‐years; IRR 2.1 [95% CI 1.4–3.0]).

Conclusion

Opportunistic infections are rare among children with JIA. Nevertheless, children with JIA had a higher rate of opportunistic infections, including an increased rate of Coccidioides, Salmonella, and herpes zoster compared to children with ADHD.

     

Longevity of insulin receptor substrate1 null mice is not associated with increased basal antioxidant protection or reduced oxidative damage

Insulin receptor substrate-1 null (Irs1 ^?/?) mice are long lived and importantly they also demonstrate increased resistance to several age-related pathologies compared to wild type (WT) controls. Currently, the molecular mechanisms that underlie lifespan extension in long-lived mice are unclear although protection against oxidative damage may be important. Here, we determined both the activities of several intracellular antioxidants and levels of oxidative damage in brain, skeletal muscle, and liver of Irs1 ^?/? and WT mice at 80, 450, and 700 days of age, predicting that long-lived Irs1 ^?/? mice would be protected against oxidative damage. We measured activities of both intracellular superoxide dismutases (SOD); cytosolic (CuZnSOD) and mitochondrial (MnSOD), glutathione peroxide (GPx), glutathione reductase (GR), catalase (CAT), and reduced glutathione (GHS). Of these, only hepatic CAT was significantly altered (increased) in Irs1 ^?/? mice. In addition, the levels of protein oxidation (protein carbonyl content) and lipid peroxidation (4-hydroxynonenal) were unaltered in Irs1 ^?/? mice, although the hepatic GSH/GSSG ratio, indicating an oxidized environment, was significantly lower in long-lived Irs1 ^?/? mice. Overall, our results do not support the premise that lifespan extension in Irs1 ^?/? mice is associated with greater tissue antioxidant protection or reduced oxidative damage.     

Antioxidant enzyme activities are not broadly correlated with longevity in 14 vertebrate endotherm species

The free radical theory of ageing posits that accrual of oxidative damage underlies the increased cellular, tissue and organ dysfunction and failure associated with advanced age. In support of this theory, cellular resistance to oxidative stress is highly correlated with life span, suggesting that prevention or repair of oxidative damage might indeed be essential for longevity. To test the hypothesis that the prevention of oxidative damage underlies longevity, we measured the activities of the five major intracellular antioxidant enzymes in brain, heart and liver tissue of 14 mammalian and avian species with maximum life spans (MLSPs) ranging from 3 years to over 100 years. Our data set included Snell dwarf mice in which life span is increased by ∼50% compared to their normal littermates. We found that CuZn superoxide dismutase, the major cytosolic superoxide dismutase, showed no correlation with MLSP in any of the three organs. Similarly, neither glutathione peroxidase nor glutathione reductase activities correlated with MLSP. MnSOD, the sole mitochondrial superoxide dismutase in mammals and birds, was positively correlated with MLSP only for brain tissue. This same trend was observed for catalase. For all correlational data, effects of body mass and phylogenetic relatedness were removed using residual analysis and Felsenstein’s phylogenetically independent contrasts. Our results are not consistent with a causal role for intracellular antioxidant enzymes in longevity, similar to recent reports from studies utilising genetic modifications of mice (Pérez et al., Biochim Biophys Acta 1790:1005–1014, 2009). However, our results indicate a specific augmentation of reactive oxygen species neutralising activities in brain associated with longevity.     

The spleen is a major site of megakaryopoiesis following transplantation of murine hematopoietic stem cells

The stem cell pool can be fractionated by using the mitochondrial dye, rhodamine-123, into Rho(low) hematopoietic stem cells and Rho(high) progenitors. Rho(low) stem cells permanently engraft all lineages, whereas Rho(high) progenitors transiently produce erythrocytes, without substantial platelet or granulocyte production. We hypothesized that the inability of the Rho(high) cells to produce platelets in vivo was due to the fact that these cells preferentially engraft in the spleen and lack marrow engraftment. Initially, we demonstrated that Rho(high) progenitors produced more megakaryocytes in vitro than Rho(low) stem cells did. To study the activity of the Rho(low) and Rho(high) subsets in vivo, we used mice allelic at the hemoglobin and glucose phosphate isomerase loci to track donor-derived erythropoiesis and thrombopoiesis. Rho(low) stem cells contributed to robust and long-term erythroid and platelet engraftment, whereas Rho(high) progenitors contributed only to transient erythroid engraftment and produced very low numbers of platelets in vivo. Donor-derived megakaryopoiesis occurred at higher densities in the spleen than in the bone marrow in animals receiving Rho(low) stem cells and peaked around day 28. Blockade of splenic engraftment using pertussis toxin did not affect the peak of splenic megakaryopoiesis, supporting the hypothesis that these megakaryocytes were derived from progenitors that originated in the bone marrow. These data emphasize that in vitro behavior of hematopoietic progenitor cell subsets does not always predict their behavior following transplantation. This study supports a major role for the spleen in thrombopoiesis following engraftment of transplanted stem cells in irradiated mice.     

Mbd4 inactivation increases Cright-arrowT transition mutations and promotes gastrointestinal tumor formation

Mbd4 (methyl-CpG binding domain 4) is a novel mammalian repair enzyme that has been implicated biochemically in the repair of mismatched G-T residues at methylated CpG sites. In addition, the human protein has been shown to interact with the DNA mismatch repair protein MLH1. To clarify the role of Mbd4 in DNA repair in vivo and to examine the impact of Mbd4 inactivation on gastrointestinal (GI) tumorigenesis, we introduced a null mutation into the murine Mbd4 gene by gene targeting. Heterozygous and homozygous Mbd4 mutant mice develop normally and do not show increased cancer susceptibility or reduced survival. Although Mbd4 inactivation did not increase microsatellite instability (MSI) in the mouse genome, it did result in a 2- to 3-fold increase in C-->T transition mutations at CpG sequences in splenocytes and epithelial cells of the small intestinal mucosa. The combination of Mbd4 deficiency with a germ line mutation in the adenomatous polyposis coli (Apc) gene increased the tumor number in the GI tract and accelerated tumor progression. The change in the GI cancer phenotype was associated with an increase in somatic C-->T mutations at CpG sites within the coding region of the wild-type Apc allele. These studies indicate that, although inactivation of Mbd4 does not by itself cause cancer predisposition in mice, it can alter the mutation spectrum in cancer cells and modify the cancer predisposition phenotype.     

An Arabidopsis histidine kinase is essential for megagametogenesis

Cytokinin-Independent 1 (CKI1) belongs to a group of putative plant histidine kinases whose members do not appear to act as ethylene receptors. The deduced protein structure, combined with the observation that Arabidopsis callus cultures overexpressing CKI1 exhibit a "cytokinin-independent" cell division and greening phenotype, led to the hypothesis that CKI1 is involved in cytokinin signaling, perhaps acting as a cytokinin receptor. To test the function of CKI1, we used a reverse-genetic approach to identify plants carrying T-DNA insertions in CKI1. Two independent alleles were identified, which produce the same developmental phenotype. Analyses of populations segregating for the cki1-5 or cki1-6 T-DNA insertion alleles failed to reveal any homozygous cki1 plants, indicating that the homozygous mutant condition was lethal. Based on segregation distortion, transmission studies, a microscopy-based examination of developing female gametophytes, and mRNA expression data, we suggest that CKI1 function is required for megagametophyte development. Our work with CKI1 mutants indicates that signal transduction by means of a HisAsp phosphorelay system may play an important and previously unsuspected role in female gametophyte development in Arabidopsis.     

Evolutionary underpinnings of excessive alcohol consumption

Given our close phylogenetic relatedness, non-human primates, in principle, could serve as an ideal model for alcoholism. Indeed, many studies in both humans and rhesus macaques show relationships between excessive alcohol consumption, aggression and serotonergic function, as measured by concentrations of the principal metabolite of serotonin, 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF). An important behavioral predictor of excessive alcohol consumption in both humans and rhesus monkeys is the propensity toward impulsivity. Integrating behavioral and neuroendocrine data from captive and semi-free-ranging rhesus macaques, we posit that benefits derived from impulsive and aggressive behaviors in some contexts might contribute indirectly to the maintenance of traits involved in alcoholism and excessive alcohol intake.     

Assessment of emergency department health care professionals' behaviors regarding HIV testing and referral for patients with STDs

The objective of this study was to evaluate human immunodeficiency virus (HIV) counseling, testing, and referral practices of emergency department health care professionals (i.e., medical doctors [MD], physician assistants [PA], nurse practitioners [NP], and registered nurses [RN]) for patients presenting with other sexually transmitted diseases (STD). All health care professionals from 10 emergency departments in a northeastern county were asked to complete an anonymous survey. The surveys were returned by 154 (41%) health care professionals (RN = 99, NP = 5, PA = 7, MD = 39, other = 4). The average years in practice were 11. Only 7% of respondents were certified to provide state mandated HIV pretest counseling (certification not required for MD). Respondents reported caring for an average of 13 patients per week with suspected STD. Fifty-five percent of respondents reported that they always or usually warn STD patients of their HIV risk, yet only 10% always or usually encouraged these patients to consent to HIV testing in their emergency department (RN = 7%, NP = 25%, PA = 0%, MD = 16%). Reasons for not offering HIV testing in their emergency department were follow-up concerns (51%), not certified to provide pretest/posttest counseling (45%), and too time consuming (19%). Twenty-seven percent of respondents indicated HIV testing was not available in their emergency department despite all hospital laboratories reporting HIV testing capability. Ninety-three percent of respondents were aware that confidential testing sites were available, but only 35% always or usually referred patients not tested in the emergency department elsewhere for testing. Emergency department health care professionals frequently fail to provide HIV counseling, testing, and/or referral for patients with suspected STD.