Urinary Monocyte Chemoattractant Protein-1 Levels and Interstitial Changes in the Renal Cortex and Their Relationship with Loss of Renal Function in Renal Transplant Patients with Delayed Graft Function

Background: Inflammatory cell infiltration and residual areas of fibrosis in kidneys after renal transplantation can lead to functional abnormalities with long-term implications. Objectives: The aim of this study was to determine urinary monocyte chemoattractant protein-1 (uMCP-1) levels, relative cortical interstitial area (RCIA), and cortical tubulointerstitial macrophage infiltration in renal transplant patients with delayed graft function (DGF) and their possible correlation with graft outcome. Design: Patients were followed after biopsies for one year, and their renal function and structure were evaluated, as well as parameters of inflammatory process. Setting: Clinical Hospital of the School of Medicine of Ribeirão Preto. Patients: Twenty-two cadaveric kidney transplant recipients with DGF were followed for one year. Measurements: Renal function, RCIA, macrophages infiltration and uMCP-1 levels were evaluated. Methods: Renal function was evaluated by plasma creatinine levels. RCIA was determined by morphometry. Immunohistochemical staining of macrophages was performed using an anti-CD68 monoclonal antibody. uMCP-1 levels were determined using a human MCP-1/CCL2 immunoassay kit. Results: There was a significant increase in uMCP-1 levels in transplant patients compared with controls ( p < 0.001). RCIA was 7.1% (6.4 to 9.2; median and 25th to 75th percentiles) in controls and 37.1% (28.1 to 43.7) in patients with kidney transplants ( p < 0.001). The patients who presented with a higher RCIA in the first biopsy showed higher levels of plasma creatinine one year after transplantation (r = 0.44; p < 0.05). The number of tubulointerstitial macrophages per 0.10 mm 2 grid field was higher in the renal cortex of transplant patients compared with the controls (19.4 (9.0 to 47.1) vs. 2.5 (1.8 to 3.4), p < 0.001). There was also a positive correlation between the RCIA and the number of tubulointerstitial macrophages in the renal cortex of these patients (r = 0.49; p < 0.001). Limitations: The number of patients studied was relatively small and may not be reflecting outcomes over a larger spectrum of kidney cadaveric transplants. Conclusions: Our results demonstrate increased levels of uMCP-1 in transplant patients with DGF, in addition to increased tubulointerstitial macrophage infiltration and RCIA, which could predict the outcome of renal function in these patients

Ten Years of Experience Training Non-Physician Anesthesia Providers in Haiti.

Surgery is increasingly recognized as an effective means of treating a proportion of the global burden of disease, especially in resource-limited countries. Often non-physicians, such as nurses, provide the majority of anesthesia; however, their training and formal supervision is often of low priority or even non-existent. To increase the number of safe anesthesia providers in Haiti, Médecins Sans Frontières has trained nurse anesthetists (NAs) for over 10 years. This article describes the challenges, outcomes, and future directions of this training program. From 1998 to 2008, 24 students graduated. Nineteen (79%) continue to work as NAs in Haiti and 5 (21%) have emigrated. In 2008, NAs were critical in providing anesthesia during a post-hurricane emergency where they performed 330 procedures. Mortality was 0.3% and not associated with lack of anesthesiologist supervision. The completion rate of this training program was high and the majority of graduates continue to work as nurse anesthetists in Haiti. Successful training requires a setting with a sufficient volume and diversity of operations, appropriate anesthesia equipment, a structured and comprehensive training program, and recognition of the training program by the national ministry of health and relevant professional bodies. Preliminary outcomes support findings elsewhere that NAs can be a safe and effective alternative where anesthesiologists are scarce. Training non-physician anesthetists is a feasible and important way to scale up surgical services resource limited settings

Effects of health and social care spending constraints on mortality in England: a time trend analysis.

OBJECTIVE: Since 2010, England has experienced relative constraints in public expenditure on healthcare (PEH) and social care (PES). We sought to determine whether these constraints have affected mortality rates. METHODS: We collected data on health and social care resources and finances for England from 2001 to 2014. Time trend analyses were conducted to compare the actual mortality rates in 2011-2014 with the counterfactual rates expected based on trends before spending constraints. Fixed-effects regression analyses were conducted using annual data on PES and PEH with mortality as the outcome, with further adjustments for macroeconomic factors and resources. Analyses were stratified by age group, place of death and lower-tier local authority (n=325). Mortality rates to 2020 were projected based on recent trends. RESULTS: Spending constraints between 2010 and 2014 were associated with an estimated 45 368 (95% CI 34 530 to 56 206) higher than expected number of deaths compared with pre-2010 trends. Deaths in those aged ≥60 and in care homes accounted for the majority. PES was more strongly linked with care home and home mortality than PEH, with each £10 per capita decline in real PES associated with an increase of 5.10 (3.65-6.54) (p<0.001) care home deaths per 100 000. These associations persisted in lag analyses and after adjustment for macroeconomic factors. Furthermore, we found that changes in real PES per capita may be linked to mortality mostly via changes in nurse numbers. Projections to 2020 based on 2009-2014 trend was cumulatively linked to an estimated 152 141 (95% CI 134 597 and 169 685) additional deaths. CONCLUSIONS: Spending constraints, especially PES, are associated with a substantial mortality gap. We suggest that spending should be targeted on improving care delivered in care homes and at home; and maintaining or increasing nurse numbers

Elevation and cholera: an epidemiological spatial analysis of the cholera epidemic in Harare, Zimbabwe, 2008-2009

BACKGROUND: In highly populated African urban areas where access to clean water is a challenge, water source contamination is one of the most cited risk factors in a cholera epidemic. During the rainy season, where there is either no sewage disposal or working sewer system, runoff of rains follows the slopes and gets into the lower parts of towns where shallow wells could easily become contaminated by excretes. In cholera endemic areas, spatial information about topographical elevation could help to guide preventive interventions. This study aims to analyze the association between topographic elevation and the distribution of cholera cases in Harare during the cholera epidemic in 2008 and 2009. METHODS: We developed an ecological study using secondary data. First, we described attack rates by suburb and then calculated rate ratios using whole Harare as reference. We illustrated the average elevation and cholera cases by suburbs using geographical information. Finally, we estimated a generalized linear mixed model (under the assumption of a Poisson distribution) with an Empirical Bayesian approach to model the relation between the risk of cholera and the elevation in meters in Harare. We used a random intercept to allow for spatial correlation of neighboring suburbs. RESULTS: This study identifies a spatial pattern of the distribution of cholera cases in the Harare epidemic, characterized by a lower cholera risk in the highest elevation suburbs of Harare. The generalized linear mixed model showed that for each 100 meters of increase in the topographical elevation, the cholera risk was 30% lower with a rate ratio of 0.70 (95% confidence interval=0.66-0.76). Sensitivity analysis confirmed the risk reduction with an overall estimate of the rate ratio between 20% and 40%. CONCLUSION: This study highlights the importance of considering topographical elevation as a geographical and environmental risk factor in order to plan cholera preventive activities linked with water and sanitation in endemic areas. Furthermore, elevation information, among other risk factors, could help to spatially orientate cholera control interventions during an epidemic

Graviton emission in Einstein-Hilbert gravity

The five-point amplitude for the scattering of two distinct scalars with the emission of one graviton in the final state is calculated in exact kinematics for Einstein-Hilbert gravity. The result, which satisfies the Steinmann relations, is expressed in Sudakov variables, finding that it corresponds to the sum of two gauge invariant contributions written in terms of a new two scalar - two graviton effective vertex. A similar calculation is carried out in Quantum Chromodynamics (QCD) for the scattering of two distinct quarks with one extra gluon in the final state. The effective vertices which appear in both cases are then evaluated in the multi-Regge limit reproducing the well-known result obtained by Lipatov where the Einstein-Hilbert graviton emission vertex can be written as the product of two QCD gluon emission vertices, up to corrections to preserve the Steinmann relations.Comment: 28 pages, LaTeX, feynmf. v2: typos corrected, reference added. Final version to appear in Journal of High Energy Physic

Tamoxifen Is Effective in the Treatment of Leishmania amazonensis Infections in Mice

Leishmaniasis is an antropozoonotic disease with a wide range of clinical manifestations. In humans, signs of disease vary from skin and mucosal ulcers to enlargement of internal organs such as the liver and spleen. The unicellular parasite Leishmania amazonensis is able to infect humans and cause localized or diffuse skin lesions. The treatment for this disease is difficult, as it requires prolonged and painful applications of toxic drugs that are poorly tolerated. Therefore, a key area in leishmaniasis research is the study of new therapeutic schemes and less toxic drugs. The present report is based on the investigation of tamoxifen's activity (a compound that has been in clinical use since the 1970s for the treatment of breast cancer) in the treatment of mice experimentally infected with L. amazonensis. We observed that infected mice treated with 20 mg/kg/day of tamoxifen for 15 days showed a significant clinical and parasitological response, with reduction in the size of lesions and ulcers and decreased numbers of parasites. These promising results pave the way for further testing of this drug as a new alternative in the chemotherapy of leishmaniasis

Comparison of the pharmacodynamic profiles of a biosimilar filgrastim and Amgen filgrastim: results from a randomized, phase I trial

Further to the patent expiry of Neupogen® (Amgen filgrastim), Hospira has developed a biosimilar filgrastim (Nivestim™) that may offer a clinically effective alternative for multiple hematologic and oncologic indications. Here results are reported from a phase I trial, primarily designed to compare the pharmacodynamic profiles of Hospira filgrastim and Amgen filgrastim. A phase I, single-center, double-blind, randomized trial was undertaken to demonstrate equivalence of the pharmacodynamic characteristics of Hospira filgrastim and Amgen filgrastim. Fifty healthy volunteers were randomized to receive 5 or 10 µg/kg dosing, before further randomization to treatment sequence. All volunteers received five daily subcutaneous doses of Hospira filgrastim or Neupogen, with subsequent crossover to the alternative treatment. Bioequivalence was evaluated by analysis of variance; if the estimated 90% confidence intervals (CIs) for the ratio of ‘test’ to ‘reference’ treatment means were within the conventional equivalence limits of 0.80–1.25, then bioequivalence was concluded. Forty-eight volunteers completed the study. Geometric mean absolute neutrophil count area under the curve from time 0 to the last time point at day 5 (primary endpoint) was comparable in volunteers given Hospira filgrastim or Amgen filgrastim at 5 µg/kg (ratio of means, 0.98; 90% CI, 0.92–1.05) or 10 µg/kg (ratio, 0.97; 90% CI, 0.93–1.01); 90% CIs were within the predefined range necessary to demonstrate bioequivalence. Hospira filgrastim was well tolerated with no additional safety concerns over Amgen filgrastim. Hospira filgrastim is bioequivalent with Amgen filgrastim with regard to its pharmacodynamic characteristics