Regulation of systemic and local neutrophil responses by G-CSF during pulmonary Pseudomonas aeruginosa infection

Granulocyte colony-stimulating factor (G-CSF) regulates the production, maturation, and function of neutrophils. Its expression is often induced during infection, resulting in high concentrations of G-CSF in inflammatory exudates and in the blood, suggesting that it may regulate both local and systemic neutrophil responses. Herein, we characterize the neutrophil response in G-CSFR(-/-) mice following intratracheal injection with Pseudomonas aeruginosa-laden agarose beads, modeling the pulmonary infection observed in many patients with cystic fibrosis. G-CSFR(-/-) mice are markedly susceptible to bronchopulmonary P aeruginosa infection, exhibiting decreased survival and bacterial clearance as well as extensive damage to lung tissue. The systemic neutrophil response was mediated primarily by enhanced neutrophil release from the bone marrow rather than increased neutrophil production and was attenuated in G-CSFR(-/-) mice. Despite normal to increased local production of inflammatory chemokines, neutrophil accumulation into the infected lung of G-CSFR(-/-) mice was markedly reduced. Moreover, the percentage of apoptotic neutrophils in the lung was elevated, suggesting that G-CSF signals may play an important role in regulating neutrophil survival at the inflammatory site. Collectively, these data provide new evidence that G-CSF signals play important but specific roles in the regulation of the systemic and local neutrophil response following infection.     

Treatment of refractory adult lymphoblastic leukemia (ALL) with 4'(9- acridinylamino) methanesulfon-M-anisidide (AMSA)

Twenty-four adults with ALL were treated with AMSA alone or in combination. Twenty-two were treated at time of relapse and two patients after failing primary induction therapy. All had been treated with anthracyclines prior to receiving AMSA. Of the 22 patients with ALL in relapse, 4 achieved a complete remission. Two of these patients have relapsed while receiving maintenance chemotherapy; one died 1 mo after achieving remission due to the occurrence of cholycystitis in the setting of pancytopenia and one patient underwent bone marrow transplantation and is in remission at 8 mo after the second remission. Both patients who failed primary induction therapy remain in remission at 11 and 36 mo, respectively. The use of AMSA should be considered for patients with ALL who fail primary induction as well as those whose leukemia becomes resistant to conventional agents.     

A cost-benefit/cost-effectiveness analysis of smoking cessation for pregnant women

Research has shown that pregnant women who smoke cigarettes increase their risk of having low birthweight (LBW) infants. Recent randomized trials indicate that women who quit smoking early in pregnancy reduce their risk of delivering a LBW infant. Using various sources, we estimated the cost-effectiveness of a smoking cessation program for preventing LBW and perinatal mortality. Assuming the program would cost $30 a participant and that 15% of the participants would quit smoking, we determined that a program offered to all pregnant smokers would shift 5,876 LBW infants to normal birthweight and would cost about $4,000 for each LBW infant prevented. Since infants born to smokers are at 20% greater risk for a perinatal death, a smoking cessation program could prevent 338 deaths at a cost of $69,542 for each perinatal death averted. Compared with the costs of caring for these LBW infants in a neonatal intensive care unit (NICU), smoking cessation programs would save $77,807,054, or $3.31 per $1 spent. The ratio of savings to costs increases to more than six to one when we include reducing long-term care for infants with disabilities secondary to LBW in the benefits from smoking cessation programs. These findings argue for routinely including smoking cessation programs in prenatal care for smokers.     

Repair of 8-oxodeoxyguanosine lesions in mitochondrial dna depends on the oxoguanine dna glycosylase (OGG1) gene and 8-oxoguanine accumulates in the mitochondrial dna of OGG1-defective mice.

Mitochondria are not only the major site for generation of reactive oxygen species, but also one of the main targets of oxidative damage. One of the major products of DNA oxidation, 8-oxodeoxyguanosine (8-oxodG), accumulates in mitochondrial DNA (mtDNA) at levels three times higher than in nuclear DNA. The main pathway for the repair of 8-oxodG is the base excision repair pathway initiated by oxoguanine DNA glycosylase (OGG1). We previously demonstrated that mammalian mitochondria from mice efficiently remove 8-oxodG from their genomes and isolated a protein from rat liver mitochondria with 8-oxoguanine (8-oxodG) DNA glycosylase/apurinic DNA lyase activity. In the present study, we demonstrated that the mitochondrial 8-oxodG DNA glycosylase/apurinic DNA lyase activity is the mitochondrial isoform of OGG1. Using mouse liver mitochondria isolated from ogg1(-/-) mice, we showed that the OGG1 gene encodes for the mitochondrial 8-oxodG glycosylase because these extracts have no incision activity toward an oligonucleotide containing a single 8-oxodG DNA base lesion. Consistent with an important role for the OGG1 protein in the removal of 8-oxodG from the mitochondrial genome, we found that mtDNA isolated from liver from OGG1-null mutant animals contained 20-fold more 8-oxodG than mtDNA from wild-type animals.     

What nurses can do to prevent or stop physical violence from patients

A common misperception is that nurses must tolerate physical violence and possible injury from patients. It is important for nurses to take action to protect both themselves and other patients.     

Preterm delivery and low birth weight among first-born infants of black and white college graduates.

Reproductive outcomes were investigated in black and white female college graduates, presumed to be of similar socioeconomic status and similar risk profile with respect to environmental factors. Data were gathered by mail survey from graduates (1973-1985) of four Atlanta, Georgia, colleges between February and June 1988. Of 6,867 alumnae to whom questionnaires were mailed, 3,084 responded. A follow-up study of black nonrespondents yielded responses from 14% (335) of those who did not respond to the mail survey. For all graduates with a first live born at the time of survey (n = 1,089), the rates of preterm delivery, low birth weight, and infant mortality were 80.8, 82.6, and 14.6 per thousand births (primigravida), respectively. Compared with white graduates, black graduates had 1.67 times the risk of preterm delivery and 2.48 times the risk of low birth weight. Measures of social and economic status differed significantly by race. However, adjustment for these variables did not reduce the estimated risk for black graduates compared with whites. Analysis of the nonresponder survey suggested that respondent data alone overestimates the incidence of adverse outcomes in blacks; using nonresponder data, relative risks of 1.28 (preterm delivery) and 1.75 (low birth weight) were calculated as lower limits of the increased risk for blacks.     

Barriers to the Administration of Epinephrine in Schools

BACKGROUND

Anaphylaxis is a serious and growing concern in the school setting as the prevalence of food allergies and food‐induced severe allergic reactions continues to increase.

METHODS

A cross‐sectional, web‐based survey was conducted regarding anaphylactic events that occurred during the 2014‐2015 school year. Eligible schools were enrolled in the EPIPEN4SCHOOLS^® program (Mylan Specialty L.P., Canonsburg, PA), which provides free epinephrine auto‐injectors to qualifying US schools. Participating schools completed a 29‐item survey on anaphylactic event occurrence and treatment, epinephrine stock, school policies regarding anaphylaxis, school staff training, and school nursing coverage.

RESULTS

Responses were provided by 12,275 schools. Epinephrine was administered on school property for 63.7% of reported anaphylactic events (1272/1998). In 38.5% (235/610) of events for which epinephrine was not used, antihistamines were cited as the reason. Only 59.4% of schools cited epinephrine as their standard first‐line therapy for anaphylaxis. School nurses were most likely to be trained in anaphylaxis recognition and permitted to administer epinephrine; however, just 53.6% of schools had a full‐time nurse on staff.

CONCLUSIONS

Process‐related barriers to the appropriate use of epinephrine go beyond access to medication. Widespread staff training and review of school policies are needed to ensure that anaphylaxis is appropriately managed in schools.