Tumor necrosis factor alpha-stimulated endothelium: an inducer of dendritic cell development from hematopoietic progenitors and myeloid leukemic cells

Especially when exposed to inflammatory stimuli, endothelial cells (EC) have been shown to promote the maturation of monocytes into dendritic cells (DC) and the long-term proliferation of CD34+ cells by constitutive cytokine production and direct cellular contact. We therefore hypothesized that cytokine-stimulated EC would induce hematopoietic progenitor cells to develop into mature dendritic cells. To test this theory, human CD34+ cells derived from cord blood or leukapheresis products were cultured with a monolayer of either interleukin (IL)-1beta, IL-4, or tumor necrosis factor (TNF)-alpha-stimulated human umbilical cord EC. The cells in suspension were analyzed weekly over a period of 6 weeks. IL-1beta supported cell expansion, whereas IL-4 had no effect on cell expansion or DC differentiation. Only TNF-alpha-stimulated EC induced the development of mature, allostimulatory DC with a high expression of CD83, HLA-DR, CD1a, and costimulatory molecules like CD80 and CD86. Acute myeloid leukemia cells from the cell line Kasumi-1 also developed DC-like features when cocultured with TNF-alpha-stimulated EC. Direct contact between endothelial and progenitor cells increased the number of developing DC. Cell cycle analysis and apoptosis studies demonstrated a reduced G2M fraction, an increased S fraction, and a decrease in TNF-alpha-dependent apoptosis of DC developing in the presence of endothelial cells. As shown by electron and confocal microscopic studies, intimate interactions between EC and DC occurred, resulting in the internalization of the developing DC within the EC monolayer and a bidirectional exchange of proteins. We conclude that, via the action of TNF-alpha, inflamed human endothelium can induce CD34+ and leukemic cells to differentiate into dendritic cells.     

Epistaxis and oral anticoagulant therapy

Epistaxis in the anticoagulated patient poses a complicated management problem, which requires interdisciplinary collaboration. The aetiology of the majority of cases of epistaxis remains idiopathic, but an ageing population and the prevalence of ischaemic heart disease and peripheral vascular disease has meant that there are increasing numbers of patients on long term oral anticoagulant therapy. This has led to a concomitant increase in the incidence of complications experienced. We have reviewed the available relevant literature and guidelines in the current management practice in this scenario. In light of this, we propose a more standardised algorithm for the management of epistaxis in this challenging group of patients.     

Quality of malnutrition assessment surveys conducted during famine in Ethiopia

Context  During 1999 and 2000, approximately 10 million people were affected by famine in Ethiopia. Results of nutrition assessments and surveys conducted by humanitarian organizations were used by donors and government agencies to determine needs for food aid and to make other decisions on geographic allocation of limited resources; however, accurate results might have been hampered by methodological errors. Objectives  To identify common methodological errors in nutrition assessments and surveys and to provide practical recommendations for improvement. Design and Setting  Nutrition assessments and surveys (n = 125) conducted by 14 nongovernmental organizations (NGOs) in 54 woredas (districts) in Ethiopia from May 1, 1999, through July 31, 2000. Surveys were ranked as valid and precise according to 5 criteria: use of population proportional to size sampling, sample size, number of clusters, number of children per cluster, and use of weight-for-height index. Main Outcome Measures  Number and proportion of surveys that used standard, internationally accepted methods and reported valid and precise results. Results  Fifty-eight of the 125 surveys (46%) were not intended to be standard 30 x 30 cluster surveys. Of the remaining 67 surveys, 6 (9%) met predetermined criteria for validity and precision. All 67 used the anthropometric index of weight-for-height, with 58 (87%) reporting z scores. Fifty-four (81%) used nonrandom sampling without consideration of population size and 6 (9%) had sample sizes of fewer than 500 persons. Conclusions  Major methodological errors were identified among 30 x 30 cluster surveys designed to measure acute malnutrition prevalence in Ethiopia during the famine of 1999-2000. Donor agencies and NGOs should be educated about the need for improved quality of nutrition assessments and their essential role in directing allocation of scarce food resources.      

Immediate total tooth replacement

Successful implant placement at the time of extraction has been documented. Implant placement at the time of extraction was initially performed as a two-stage procedure often with barrier membranes and sophisticated second-stage surgical uncoverings. The authors describe the next generation of this technique, including atraumatic tooth removal with simultaneous root form, implant placement, and temporization at one appointment. This technique of "Immediate Total Tooth Replacement" allows for the maintenance of the bony housing and soft-tissue form that existed before extraction, while at the same time establishing a root form anchor in the bone for an esthetic restoration.     

Developing public health indicators in complex emergency response

During the past decade, indicators for the assessment, monitoring, and evaluation of services provided by humanitarian organizations to populations affected by complex emergencies (CEs) were developed to improve the effectiveness and accountability of humanitarian response. The quality of data used to develop individual indicators and their relationship to positive health outcomes varies greatly. This article states the essential characteristics necessary for the development and implementation of effective indicators in CE response and proposes the establishment of an evidence-based grading system. The importance of trend analysis and the modification or addition of various indicators and their thresholds, according to phase and location of CEs, are stressed. Limitations in the development, implementation, and interpretation of these indicators, including those outside of the organizations' control are discussed. More evidence-based research is needed as to the type and thresholds of indicators that lead to improved health outcomes in populations affected by CEs. The use of indicators by non-governmental organizations, and how they affect their program's decision-making in different phases and settings within CEs need further study. Finally, the establishment of a regulating body with the authority to enforce the attainment of standards by use of these indicators is necessary to avoid inappropriate humanitarian assistance causing loss of life in the future.     

Preliminary study of therapeutic efficacy of a new fasciolicidal drug derived from Commiphora molmol (myrrh)

Myrrh (from the stem of the Commiphora molmol tree) is an oleo gum resin that may prove efficacious for the treatment of fascioliasis. We studied 7 patients who were passing Fasciola eggs in their stools and treated them with myrrh. The drug (a formulation consisting of 8 parts of resin and 3.5 parts of volatile oils, all extracted from myrrh) was given in a dose of 12 mg/kg per day for 6 consecutive days in the morning on an empty stomach. Patients were followed for 3 months. The therapy proved to be effective, with pronounced improvement of the general condition and amelioration of all symptoms and signs. A dramatic drop in the egg count was detected at the end of treatment. Eggs were no longer detectable in the feces 3 weeks after treatment and after a follow-up period of 3 months. High eosinophilic counts, elevated liver enzymes, and Fasciola antibody titers returned to nearly normal. No signs of toxicity or adverse effects were observed. We conclude that the formulation of myrrh is safe, well tolerated, and effective for treating fascioliasis.     

The distribution of refractory periods influences the dynamics of ventricular fibrillation

The spatial and dynamic properties of ventricular fibrillation (VF) may be random or related to cellular electrical properties of the normal heart. Local activation intervals (AIs) in VF may depend on the local refractory period (RP), and sustained VF may require a steep action potential (AP) restitution curve. In guinea pig hearts, AP durations (APDs) and RPs on the epicardium are shorter at the apex and progressively longer toward the base, producing gradients of RPs that may influence the spatial organization of VF. In the present study, the influence of APDs on VF dynamics is investigated in perfused guinea pig hearts stained with a voltage-sensitive dye by comparing APD gradients to the dynamics of VF elicited by burst pacing. In VF, AIs had no clear periodicity, but average AIs were shorter at the apex (57.5+/-8.1 ms) than the base (76.1+/-1.5 ms, n=6, P<0.05) and had gradients similar to APD gradients (correlation coefficient 0.71+/-0.04). Analysis of local velocity vectors showed no preferential directions, and fast Fourier transform (FFT) power spectra were broad (10 to 24 Hz) with multiple peaks (n=6). However, the selective inhibition of delayed K(+) rectifying currents, I(Kr) (E4031; 0.5 micromol/L, n=3), shifted FFT spectra from complex to a lower dominant frequency (10 Hz) and altered repolarization but retained the correlation between mean AIs and RPs. Thus, VF dynamics are consistent with a multiple wave-make and wave-break mechanism, and the local RP influences VF dynamics by limiting the range of VF frequencies and AIs at each site. The full text of this article is available at http://www.circresaha.org.