Interleukin-3 treatment of rhesus monkeys leads to increased production of histamine-releasing cells that express interleukin-3 receptors at high levels

To understand the hematopoietic and nonhematopoietic responses to interleukin-3 (IL-3), expression of cell-surface IL-3 receptors (IL-3R) was examined on bone marrow (BM) cells and peripheral blood (PB) cells of rhesus monkeys during the course of in vivo IL-3 treatment. Whereas IL-3R expression is low in untreated monkeys, IL-3 administration led to a gradual increase in both low- and high-affinity binding sites for IL-3. This increase reflected the total number of cells expressing IL- 3Rs, as detected by flow cytometry using biotinylated IL-3. Most of these IL-3R+ cells in both BM and PB could be characterized as basophilic granulocytes that contained high levels of histamine. In contrast to the effect on these differentiated cells, IL-3 administration did not significantly alter the low level IL-3R expression on immature, CD34+ cells. Further flow cytometric analysis using biotinylated growth factors showed that the IL-3R+ basophils also expressed receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), but not for IL-6 or Kit ligand. These findings indicated that the IL-3R+ cells included neither monocytes, which express GM-CSFRs and IL-6Rs abundantly, nor mast cells, which express c- kit. By combining flow cytometric and Scatchard data, it was calculated that the basophils contain as many as 1 to 2 x 10(3) high-affinity IL- 3Rs and 15 to 30 x 10(3) low-affinity sites. The finding that in vivo IL-3 treatment leads to the production of large numbers of cells that express high levels of IL-3R and are capable of producing histamine provides an explanation for the often severe allergic reactions that occur during prolonged IL-3 administration. It also indicates that IL- 3, in addition to its direct effects on hematopoietic cells, may also stimulate hematopoiesis through the release of secondary mediators such as histamine by IL-3-responsive mature cells.     

Deaths Attributable to Carbapenem-Resistant Enterobacteriaceae Infections

We evaluated the number of deaths attributable to carbapenem-resistant Enterobacteriaceae by using studies from around the world published before April 9, 2012. Attributable death was defined as the difference in all-cause deaths between patients with carbapenem-resistant infections and those with carbapenem-susceptible infections. Online databases were searched, and data were qualitatively synthesized and pooled in a metaanalysis. Nine studies met inclusion criteria: 6 retrospective case–control studies, 2 retrospective cohort studies, and 1 prospective cohort study. Klebsiella pneumoniae was the causative pathogen in 8 studies; bacteremia was the only infection in 5 studies. We calculated that 26%–44% of deaths in 7 studies were attributable to carbapenem resistance, and in 2 studies, which included bacteremia and other infections, −3% and −4% of deaths were attributable to carbapenem resistance. Pooled outcomes showed that the number of deaths was significantly higher in patients with carbapenem-resistant infections and that the number of deaths attributable to carbapenem resistance is considerable.     

Residual Periodontal Ligament in Extracted Teeth – Is It Associated With Indication for Extraction?

BackgroundPeriodontal disease is a major cause of tooth loss. Few studies have evaluated the residual area of the periodontal ligament in extracted teeth and, to the best of our knowledge, none from Latin America have done so regarding indications for extraction. The aim of this study was to evaluate the residual periodontal ligament (RPL) with respect to indication for extraction in a sample of teeth from a Brazilian Public Health Service district.Materials and methodsAll teeth extracted within the Public Health Service district of Santa Maria, Brazil, over a 5-month period were requested for analysis. A total of 414 teeth eligible for measurement were stained and evaluated for RPL using a stereo microscope. Participating Public Health Service dentists completed a questionnaire detailing demographic variables and indication for each extracted tooth. The percentage of RPL was determined for each tooth. Comparisons of RPL between teeth extracted on periodontal versus other indications were made using the Mann-Whitney test.ResultsRPL averaged 34.8% for teeth extracted on periodontal indications versus 79.5% for other teeth (P ≤ 0.001). When considering teeth with an RPL ≥ 30% as possible to maintain, 189 (76%) of the teeth extracted on periodontal indications could have been maintained. When RPL cut-off limits of ≥ 40% or ≥ 50% are applied, 93 (37%) and 43 (17%) teeth, respectively, could have been maintained.ConclusionThis study suggests that strictly based on RPL, a large number of teeth extracted on periodontal indications conceivably could be maintained.Key words: Cross-sectional studies, Prognosis, Tooth extraction, Tooth loss     

Anxiety,depression, and stress in caregivers of children and adolescents with mental disorders in Ghana and implications for medication adherence

ObjectiveThis study assessed levels of anxiety, depression, and stress among family caregivers of children and adolescents with mental disorders in Ghana and the implication on medication adherence.DesignA cross-sectional study.SettingThe study was conducted at the outpatient departments of the three main public psychiatric hospitals in Ghana.ParticipantsTwo hundred and ten non-paid family caregivers of children and adolescents with mental disorders were recruited for this study.Main Outcome MeasureThe study assessed symptoms of anxiety, depression and stress among the caregivers and estimated caregiver-reported medication adherence.ResultsAbout 56.2%, 66.2% and 78% of the caregivers experienced severe anxiety, severe depression and moderate to severe stress symptoms respectively. From the multiple logistic regression model, while anxiety was significantly affected by religion and education, depression was influenced by sex, age, marital status, proximity to facility, and employment status. Female caregivers had about four times higher odds of being depressed compared to male caregivers (aOR: 3.81, 95% CI: 1.66 – 8.75). The caregiver-reported medication adherence was 11.9%. Anxiety was significantly predictive of medication adherence.ConclusionMost family caregivers of children and adolescents with mental disorders experienced symptoms of anxiety, depression and stress with anxiety having implications for medication adherence. The study findings underscore the need to consider psychological characteristics of caregivers and the provision of mental health support for them, as part of the routine health care for children and adolescents with mental disorders.FundingNone indicated     

Toxicity after prolonged (more than four weeks) administration of intravenous colistin

Background  

The intravenous use of polymyxins has been considered to be associated with considerable nephrotoxicity and neurotoxicity. For this reason, the systemic administration of polymyxins had been abandoned for about 20 years in most areas of the world. However, the problem of infections due to multidrug-resistant (MDR) Gram-negative bacteria such us Pseudomonas aeruginosa and Acinetobacter baumanniii has led to the re-use of polymyxins. Our objective was to study the toxicity of prolonged intravenous administration of colistin (polymyxin E).