The effect of crystalloid versus medium molecular weight colloid solution on post-operative nausea and vomiting after ambulatory gynecological surgery - a prospective randomized trial.

UNLABELLED: ABSTRACT: BACKGROUND: Intravenous fluid is recommended in international guidelines to improve patient post-operative symptoms, particularly nausea and vomiting. The optimum fluid regimen has not been established. This prospective, randomized, blinded study was designed to determine if administration of equivolumes of a colloid (hydroxyethyl starch 130/0.4) reduced post operative nausea and vomiting in healthy volunteers undergoing ambulatory gynecologic laparoscopy surgery compared to a crystalloid solution (Hartmann\u27s Solution). METHODS: 120 patients were randomized to receive intravenous colloid (N = 60) or crystalloid (N = 60) intra-operatively. The volume of fluid administered was calculated at 1.5 ml.kg-1 per hour of fasting. Patients were interviewed to assess nausea, vomiting, anti-emetic use, dizziness, sore throat, headache and subjective general well being at 30 minutes and 2, 24 and 48 hours post operatively. Pulmonary function testing was performed on a subgroup. RESULTS: At 2 hours the proportion of patients experiencing nausea (38.2 % vs 17.9%, P = 0.03) and the mean nausea score were increased in the colloid compared to crystalloid group respectively (1.49 ± 0.3 vs 0.68 ± 0.2, P = 0.028). The incidence of vomiting and anti-emetic usage was low and did not differ between the groups. Sore throat, dizziness, headache and general well being were not different between the groups. A comparable reduction on post-operative FVC and FEV-1 and PEFR was observed in both groups. CONCLUSIONS: Intra-operative administration of colloid increased the incidence of early postoperative nausea and has no advantage over crystalloid for symptom control after gynaecological laparoscopic surgery

The histone deacetylase inhibitor Trichostatin A modulates CD4+ T cell responses

BACKGROUND: Histone deacetylase inhibitors (HDACIs) induce hyperacetylation of core histones modulating chromatin structure and affecting gene expression. These compounds are also able to induce growth arrest, cell differentiation, and apoptotic cell death of tumor cells in vitro as well as in vivo. Even though several genes modulated by HDAC inhibition have been identified, those genes clearly responsible for the biological effects of these drugs have remained elusive. We investigated the pharmacological effect of the HDACI and potential anti-cancer agent Trichostatin A (TSA) on primary T cells. METHODS: To ascertain the effect of TSA on resting and activated T cells we used a model system where an enriched cell population consisting of primary T-cells was stimulated in vitro with immobilized anti-CD3/anti-CD28 antibodies whilst exposed to pharmacological concentrations of Trichostatin A. RESULTS: We found that this drug causes a rapid decline in cytokine expression, accumulation of cells in the G(1 )phase of the cell cycle, and induces apoptotic cell death. The mitochondrial respiratory chain (MRC) plays a critical role in the apoptotic response to TSA, as dissipation of mitochondrial membrane potential and reactive oxygen species (ROS) scavengers block TSA-induced T-cell death. Treatment of T cells with TSA results in the altered expression of a subset of genes involved in T cell responses, as assessed by microarray gene expression profiling. We also observed up- as well as down-regulation of various costimulatory/adhesion molecules, such as CD28 and CD154, important for T-cell function. CONCLUSIONS: Taken together, our findings indicate that HDAC inhibitors have an immunomodulatory potential that may contribute to the potency and specificity of these antineoplastic compounds and might be useful in the treatment of autoimmune disorders

Developmentally regulated interactions of human thymocytes with different laminin isoforms

The gene family of heterotrimeric laminin molecules consists of at least 15 naturally occurring isoforms which are formed by five different α, three β and three γ subunits. The expression pattern of the individual laminin chains in the human thymus was comprehensively analysed in the present study. Whereas laminin isoforms containing the laminin α1 chain (e.g. LN-1) were not present in the human thymus, laminin isoforms containing the α2 chain (LN-2/4) or the α5 chain (LN-10/11) were expressed in the subcapsular epithelium and in thymic blood vessels. Expression of the laminin α4 chain seemed to be restricted to endothelial cells of the thymus, whereas the LN-5 isoform containing the α3 chain could be detected on medullary thymic epithelial cells and weakly in the subcapsular epithelium. As revealed by cell attachment assays, early CD4(−) CD8(−) thymocytes which are localized in the thymus beneath the subcapsular epithelium adhered strongly to LN-10/11, but not to LN-1, LN-2/4 or LN-5. Adhesion of these thymocytes to LN-10/11 was mediated by the integrin α6β1. During further development, the cortically localized CD4(+) CD8(+) thymocytes have lost the capacity to adhere to laminin-10/11. Neither do these cells adhere to any other laminin isoform tested. However, the more differentiated single positive CD8(+) thymocytes which were mainly found in the medulla were able to bind to LN-5 which is expressed by medullary epithelial cells. Interactions of CD8(+) thymocytes with LN-5 were integrin α6β4-dependent. These results show that interactions of developing human thymocytes with different laminin isoforms are spatially and developmentally regulated

How Far Is the Sternal Angle from the Mid-right Atrium?

BACKGROUND: The central venous pressure (CVP) is commonly estimated at the bedside by measuring the height of the jugular venous pressure (JVP) relative to the sternal angle. Determining the CVP from this measure requires that the distance from the sternal angle to the level of the mid-right atrium be known. Classical clinical teaching quotes this distance as 5 cm, invariable between patients, and invariable with changes in the elevation of the patient's head. The validity of these JVP characteristics has been questioned. OBJECTIVES: To measure the distance from the sternal angle to the level of the mid-right atrium (SA-RA) and determine if the SA-RA distance varies with patient position. METHODS: Cross-sectional study conducted at a single-center teaching hospital on ambulatory patients undergoing computed tomography of the chest. RESULTS: One hundred sixty patients were included. The median SA-RA distance with the patient lying supine was 5.4 cm (interquartile range, 4.7 to 6.1). Using geometric calculations to estimate the SA-RA distance when the patient's torso was elevated above the supine position, the median SA-RA distance was calculated to be 8 cm, 9.7 cm, and 9.8 cm at 30, 45, and 60 degrees elevation respectively. The SA-RA distance varied extensively between patients and was independently associated with smoking, age, and antero-posterior chest diameter. CONCLUSIONS: The distance from the sternal angle to the level of the mid-right atrium varies considerably between individuals and with patient position. When using the JVP to calculate the CVP, physicians need to consider specific patient factors and the patient's position