The European Histamine Research Society43rd Annual Meeting,May 7–10, 2014Lyon,France

Idiopathic nephrotic syndrome (INS) is a multifactorial disease, characterized by proteinuria, hypoalbuminemia, edema and hyperlipidemia. Studies in humans and animal models have associated INS with changes in the immune response. The purpose of this article is to review clinical and experimental findings showing the involvement of the immune response in the pathogenesis of INS. The role of the immune system in INS has been shown by clinical and experimental studies. However, the pattern of immune response in patients with INS is still not clearly defined. Many studies show changes in the dynamics of T lymphocytes, especially the regulatory T cells. Alternatively, there are other reports regarding the involvement of the complement system and B lymphocytes in the pathophysiology of INS. Indeed, none of the immunological biomarkers evaluated were undeniably linked to changes in glomerular permeability and proteinuria. On the other hand, some studies suggest a link between urinary chemokines, such as IL-8/CXCL8 and MCP-1/CCL2, and changes in glomerular permeability and/or the deterioration of glomerulopathies. To understand the pathophysiology of INS, longitudinal studies are clearly needed. The characterization of the profile of the immune response might help the development of specific and individualized therapies, leading to clinical improvement and better prognosis.     

The Waterlow score for risk assessment in surgical patients

Introduction

Perioperative scoring systems aim to predict outcome following surgery and are used in preoperative counselling to guide management and to facilitate internal or external audit. The Waterlow score is used prospectively in many UK hospitals to stratify the risk of decubitus ulcer development. The primary aim of this study was to assess the potential value of this existing scoring system in the prediction of mortality and morbidity in a general surgical and vascular cohort.

Methods

A total of 101 consecutive moderate to high risk emergency and elective surgical patients were identified through a single institution database. The preoperative Waterlow score and outcome data pertaining to that admission were collected. The discriminatory power of the Waterlow score was compared against that of the American Society of Anesthesiologists (ASA) grade and the Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (P-POSSUM).

Results

The inpatient mortality rate was 17% and the 30-day morbidity rate was 29%. A statistically significant association was demonstrated between the preoperative Waterlow score and inpatient mortality (p<0.0001) and 30-day morbidity (p=0.0002). Using a threshold Waterlow score of 20 to dichotomise risk, accuracies of 0.84 and 0.76 for prediction of mortality and morbidity were demonstrated. In comparison with P-POSSUM, the preoperative Waterlow score performed well on receiver operating characteristic analysis. With respect to mortality, the area under the curve was 0.81 (0.80–0.85) and for morbidity it was 0.72 (0.69–0.76). The ASA grade achieved a similar level of discrimination.

Conclusions

The Waterlow score is collected routinely by nursing staff in many hospitals and might therefore be an attractive means of predicting postoperative morbidity and mortality. It might also function to stratify perioperative risk for comparison of surgical outcome data. A prospective study comparing these risk prediction scores is required to support these findings.     

Role of preoperative carbohydrate loading: a systematic review

INTRODUCTION

Surgical stress in the presence of fasting worsens the catabolic state, causes insulin resistance and may delay recovery. Carbohydrate rich drinks given preoperatively may ameliorate these deleterious effects. A systematic review was undertaken to analyse the effect of preoperative carbohydrate loading on insulin resistance, gastric emptying, gastric acidity, patient wellbeing, immunity and nutrition following surgery.

METHODS

All studies identified through PubMed until September 2011 were included. References were cross-checked to ensure capture of cited pertinent articles.

RESULTS

Overall, 17 randomised controlled trials with a total of 1,445 patients who met the inclusion criteria were identified. Preoperative carbohydrate drinks significantly improved insulin resistance and indices of patient comfort following surgery, especially hunger, thirst, malaise, anxiety and nausea. No definite conclusions could be made regarding preservation of muscle mass. Following ingestion of carbohydrate drinks, no adverse events such as apparent or proven aspiration during or after surgery were reported.

CONCLUSIONS

Administration of oral carbohydrate drinks before surgery is probably safe and may have a positive influence on a wide range of perioperative markers of clinical outcome. Further studies are required to determine its cost effectiveness.     

Transforming growth factor-beta trans-modulates the expression of colony stimulating factor receptors on murine hematopoietic progenitor cell lines

Transforming growth factor beta (TGF-beta) is a potent and selective growth inhibitor of early hematopoietic progenitors and leukemic cells. The cellular mechanism(s) underlying this antiproliferative effect is, however, currently unknown. In the present study, we demonstrate that TGF-beta inhibits the expression of granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin 3 (IL-3), and granulocyte-CSF (G-CSF) receptors on murine factor-dependent and independent hematopoietic progenitor cell lines without a significant change in receptor affinity. A maximum reduction in GM-CSF receptor numbers of 65% to 77% was observed by 96-hour incubation with TGF-beta. The TGF- beta induced trans-down-modulation of GM-CSF receptors was prolonged, noncytotoxic but reversible, and not due to endogenous production of GM- CSF. The TGF-beta induced reduction in CSF receptor numbers preceded TGF-beta's growth inhibitory action. In addition, the ED50 (1 to 10 pmol/L) for TGF-beta's CSF receptor modulatory and antiproliferative effect was similar. The effect of TGF-beta on cell surface CSF receptor expression was specific, because the expression of other cell surface proteins (Ly 5 and Ly 17) was not affected by TGF-beta treatment, and because other growth inhibitors (tumor necrosis factor and interferon) did not affect CSF receptor expression. These data suggest that the downregulation of the growth of hematopoietic progenitor cells by TGF- beta involves reducing the cell surface expression on growth factor receptors.     

Detection of the hemoglobin E mutation using the color complementation assay: application to complex genotyping

The color complementation assay (CCA) is a method of allele-specific DNA amplification by which competitive priming and extension of fluorescently labeled oligonucleotide primers determine the color of DNA amplification product. This diagnostic method precludes the need for radioisotopes, electrophoresis, and multiple high-stringency reaction conditions. The multiplicity of mutant globin genes present in Southeast Asians complicates clinical diagnosis and underscores the importance of DNA-based diagnostic methods. We have applied CCA to distinguish beta A and beta E alleles. Competing 15mer primers were a fluorescein-labeled complement to beta A and a rhodamine-labeled complement to beta E, identical except for their central nucleotides. A common unlabeled primer was used to amplify DNA product, the color of which was determined by the perfectly complementary primer. Color photography and spectrofluorometry, as well as a method of black-white photography that we developed to distinguish fluorescein- and rhodamine- labeled DNA, were used to record results. We applied CCA to define the complex genotype of a Thai woman with thalassemia intermedia, 96% HbE, and 4% HbF whose possible genotypes included several permutations of alpha-thalassemia, beta-thalassemia, and beta E genes. zeta-Globin gene mapping of DNA doubly digested with Bg/II and Asp 718 showed the -alpha 3.7/--SEA genotype, and CCA confirmed homozygous beta E/beta E. The CCA is useful for diagnosing the compound hemoglobin genotypes of Southeast Asians and could be applied also to prenatal diagnosis in this population.     

DLA-identical bone marrow grafts after low-dose total body irradiation: the effect of canine recombinant hematopoietic growth factors

Previous studies found that bone marrow (BM) allografts from DLA- identical littermates resulted in survival of two thirds of recipient dogs after otherwise lethal doses of 450 to 600 cGy of total body irradiation (TBI) because of successful allografts or autologous recovery after rejection of the allografts. The current study asked whether survival could be further improved by treating allograft recipients with recombinant canine granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF), or G-CSF/SCF. Of 21 dogs, 14 (67%) receiving allografts but no growth factors survived, 10 with successful allografts (including 5 mixed chimeras) and 4 with autologous recovery; whereas 7 animals died, 5 from infections during BM aplasia and 2 from acute graft-versus-host disease. By comparison, 30 of 34 dogs (88%) receiving hematopoietic growth factors in addition to the BM graft survived, 17 with successful allografts (including 10 mixed chimeras) and 13 with autologous recovery; whereas 4 died, all with infection related to BM aplasia after rejection of the allograft. Survival was similar for recipients of G-CSF, SCF, or the combination of G-CSF and SCF. Logistic regression analyses, which accounted for possible effects of TBI dose, showed a trend for improved survival in dogs receiving growth factors (P = .09), no change in allogeneic engraftment (P = .74), and a slight increase in autologous recovery (P = .22). In agreement with previous data, we found that grafts of BM from DLA-identical littermates improved survival of recipient dogs exposed to low but otherwise lethal doses of TBI. A further improvement in survival could be achieved by additional treatment with G-CSF, SCF, or G-CSF/SCF. Results suggest that treatment by hematopoietic growth factors along with BM grafts should be considered for victims of radiation accidents.     

A significant incidental finding on cone beam computed tomography: multiple myeloma

Cone beam computed tomography is widely used in dentistry. Incidental findings are common, with many requiring intervention or monitoring. We present a rare case of previously undiagnosed, asymptomatic multiple myeloma first identified incidentally on cone beam computed tomography and panoramic radiography. This case highlights the diverse range of lesions that may appear on cone beam computed tomography and the importance of radiologic interpretation.