Activation of the kallikrein-kinin system after endotoxin administration to normal human volunteers

The objective of this study was to determine the role of the kallikrein- kinin system in healthy humans after intravenous administration of either Escherichia coli endotoxin or saline. We studied a total of 18 healthy nonsmoking volunteers, 23 to 38 years old, in an open-label study at the Critical Care Medicine Department, Clinical Center, National Institutes of Health (Bethesda, MD) in which some of the patients served as their own controls. After baseline data collection, the subjects received intravenously either E coli endotoxin (n = 15, 4 ng/kg of body weight) or saline (n = 8, controls). Signs, symptoms, systemic blood pressure, factor XII, plasma prekallikrein (PK), factor XI (FXI), antithrombin III (AT-III), high molecular weight kininogen (HK), and alpha 2-macroglobulin-kallikrein complexes were measured at baseline and 1, 2, 3, 5, and 24 hours after injection of either saline or endotoxin. After infusion of endotoxin, we found the functional plasma levels of FXI decreased at 2 hours (P < .05) and at 5 hours (P < .05). Functional PK was significantly depressed by 2 hours (P < .05), at 5 hours (P < .05), and at 24 hours (P < .01), whereas the PK antigen was only low at 5 hours (P < .05). These changes were accompanied by a significant increase in circulating alpha 2-macroglobulin-kallikrein complexes at 3 hours (P < .05) and 5 hours (P < .01). No significant changes occurred in the plasma levels of factor XII or HK. We concluded that clinical response to intravenous endotoxin in healthy human volunteers is associated with activation of the kallikrein-kinin systems. Further investigation is needed with specific inhibitors of the kallikrein-kinin system to define its primary or secondary role in the endotoxin-mediated reactions.     

Three-dimensional assessment of hand outcome

IntroductionPatient reported outcome measures are central to National Health Service quality of care assessments. This study investigated the benefit of elective hand surgery by the simultaneous analysis of pain, function and appearance, using a three-dimensional (3D) graphical model for evaluating and presenting outcome.MethodsA total of 188 patients scheduled for surgery completed pre- and postoperative questionnaires grading the severity of their pain, dysfunction and deformity of their hand(s). Scores were plotted on a 3D graph to demonstrate the degree of ‘normalisation’ following surgery.ResultsSurgical groups included: nerve compression (n=53), Dupuytren’s disease (n=51), trigger finger (n=20), ganglion (n=17) or other lump (n=21), trapeziometacarpal joint osteoarthritis (n=10), rheumatoid disease (n=5) and other pathology (n=13). A significant improvement towards normality was seen after surgery in each group except for patients with rheumatoid disease.ConclusionsThis study provides a simple, visual representation of hand surgery outcome by plotting patient scores for pain, function and appearance simultaneously on a 3D graph.     

Intact fibroblast growth factor 23 and fragments in plasma from Gambian children

Summary

Fibroblast growth factor 23 (FGF23) is grossly elevated in Gambian children with rickets and, at a lower prevalence, in those without bone deformities. We used western blotting to mimic the detection capabilities of the C-terminal FGF23 enzyme-linked immunosorbent assay (ELISA). Only intact FGF23 hormone was present in Gambian plasma samples from children with and without rickets.

Introduction

Elevated circulating FGF23 concentrations have been detected in plasma samples from Gambian children using the C-terminal Immutopics ELISA. The Immutopics ELISA detects both the intact FGF23 hormone and the C-terminal fragment. The aim of this study was to determine whether the elevated FGF23 concentrations as detected by the ELISA were predominantly due to a high proportion of intact FGF23 hormone and/or C-terminal FGF23 fragments.

Methods

Stored, frozen plasma samples from previous studies of Gambian children with known concentrations of FGF23 as determined by C-terminal Immutopics ELISA assay, were selected for western blotting analysis: from children with rickets-like bone deformities (n?=?4) and local controls (n?=?4), with elevated >900 RU/ml (n?=?2) and normal <30 RU/ml (n?=?2; from each group). The anti-FGF23 polyclonal antibody that recognizes the C-terminal of FGF23 (as used in the Immutopics kit) was used as the primary antibody and the anti-IgG polyclonal antibody conjugated to horseradish peroxidase (HRP) was used as the secondary antibody.

Results

Firstly, C-terminal FGF23 fragments, although detectable in standards from the Immutopics ELISA kit, were not in the Gambian plasma samples. Secondly, there was no difference in the size of FGF23 molecules present in plasma from children with rickets-like bone deformities and children from the local community.

Conclusions

Western blotting has provided evidence that elevated FGF23 concentrations, as determined by the C-terminal Immutopics ELISA, measured in Gambian children with and without rickets-like bone deformities was not caused by an increased proportion of circulating inactive C-terminal fragments.     

Use of medical emergency team responses to reduce hospital cardiopulmonary arrests

Background: Medical emergency team (MET) responses have been implemented to reduce inpatient mortality, but data on their efficacy are sparse and there have been no reports to date from US hospitals.

Objectives: To determine how the incidence and outcomes of cardiac arrests have changed following increased use of MET.

Methods: Objective criteria for MET activation were created and disseminated as part of a crisis management program, after which there was a rapid and sustained increase in the use of MET. A retrospective analysis of clinical outcomes was performed to compare the incidence and mortality of cardiopulmonary arrest before and after the increased use of MET.

Results: A retrospective analysis of 3269 MET responses and 1220 cardiopulmonary arrests over 6.8 years showed an increase in MET responses from 13.7 to 25.8 per 1000 admissions (p<0.0001) after instituting objective activation criteria. There was a coincident 17% decrease in the incidence of cardiopulmonary arrests from 6.5 to 5.4 per 1000 admissions (p = 0.016). The proportion of fatal arrests was similar before and after the increase in use of MET.

Conclusions: Increased use of MET may be associated with fewer cardiopulmonary arrests.

     

Bifid origin of the left vertebral artery

Two patients demonstrating a bifid origin of the left vertebral artery are described. The embryologic origin of this anomaly is reviewed together with diagnostic and therapeutic implications, emphasizing the importance of knowledge and recognition of the anomaly. It is suggested that this anomaly is not as rare as previously thought.