Anakinra treats fulminant myocarditis from Neisseria meningitidis septicaemia and haemophagocytic lymphohistiocytosis: a case report

Background: Fulminant myocarditis is a life-threatening condition characterized by acute cardiac dysfunction requiring pharmacological or mechanical circulatory support. Haemophagocytic lymphohistiocytosis (HLH) is an uncommon state of immune dysregulation and overactivation. Inflammation mediated by interleukin-1 (IL-1) is thought to play a role in the pathogenesis of myocarditis and HLH, and there is some evidence that the IL-1 receptor antagonist Anakinra may play a role in treating both these conditions. Case summary: A 26-year-old previously healthy male presented to the Emergency Department with a 3-day history of malaise, headache, vomiting, diarrhoea, and fever. He was profoundly hypotensive on arrival, diagnosed with septic shock, and commenced on broad-spectrum antibiotics and vasopressors. Blood tests showed lymphopenia, thrombocytopenia, low fibrinogen and elevated high sensitivity troponin T, ferritin, and C-reactive protein. Echocardiography demonstrated severely impaired biventricular systolic function and a diagnosis of fulminant myocarditis was made. His condition deteriorated and he required intubation and additional inotropic support. A diagnosis of HLH was made and he was commenced on Anakinra and Methylprednisolone. His condition improved rapidly thereafter. Polymerase chain reaction testing subsequently confirmed infection with Neisseria meningitidis. Discussion: In this case, fulminant myocarditis and HLH were life-threatening manifestations of meningococcal septicaemia, and the patient’s condition improved rapidly following administration of the IL-1 receptor antagonist Anakinra. These complications should be borne in mind in septic patients with marked haemodynamic instability and multiorgan dysfunction, and treatment with Anakinra should be considered in those who fail to respond to conventional therapy

A Child's Concept of Pain: An International Survey of Pediatric Pain Experts.

A child's 'concept of pain' refers to how they understand what pain actually is, what function pain serves, and what biological processes are thought to underpin it. We aimed to determine pediatric pain experts' opinions of: (1) the importance and usefulness of assessing a child's concept of pain in clinical and/or research settings; (2) the usefulness of the content of items within currently published adult-targeted resources for assessing a child's concept of pain; and (3) important domains of a child's concept of pain to assess. Forty-nine pediatric pain experts (response rate = 75.4%) completed an online survey. Descriptive statistics and frequency of responses were analyzed. Experts from all included disciplines reported that assessing a child's concept of pain is important and useful both clinically and in a research setting (>80% reported very or extremely useful for each item). Experts considered that the content of 13 items from currently published adult-targeted resources was useful, but the wording was too complex for children aged 8-12 years. Experts considered that all seven of the proposed domains of a child's concept of pain was important to assess. The findings can be used to inform the development of an assessment tool for a child's concept of pain

Mercury chemostratigraphy across the Cambrian Series 2 – Series 3 boundary: evidence for increased volcanic activity coincident with extinction?

Flood basalt volcanism represented by the Kalkarindji Province (Australia) is temporally associated with a trilobite mass extinction at the Cambrian Series 2 – Series 3 boundary, providing one of the oldest potential links between volcanism and biotic crisis in the Phanerozoic. However, the relative timing of flood basalt volcanism (Kalkarindji Province, Australia) and the trilobite extinctions, first recorded in North America, is not known. Mercury (Hg) enrichment in the sedimentary record provides a potential proxy for volcanism which may facilitate improved chronologies of eruption and extinction. Here we report mercury records for three sections from mid-shelf strata of the Great Basin (western USA) that straddle the Series 2 – Series 3 boundary. One section (Oak Springs Summit, NV) features a Hg enrichment at the start of the extinction interval, but mercury anomalies are also present at lower levels. These older anomalies may record either earlier phases of Kalkarindji volcanism, eruptions in other locations, or may be the result of sedimentary and/or diagenetic processes affecting the Hg record. In the Carrara Formation at Emigrant Pass, CA, the precise extinction horizon is not well defined, but a carbon isotope anomaly (the Redlichiid-Olenellid Extinction Carbon isotope Event; ROECE) provides a stratigraphic tie point to the Oak Springs Summit section. At Emigrant Pass, Hg enrichments precede the ROECE interval and are absent in the inferred extinction zone. The Pioche Formation at Ruin Wash, NV, lacks Hg enrichment at the extinction horizon but contains older enrichments. The inconsistent Hg records between the three sections demonstrate that factors controlling Hg accumulation and preservation in marine sedimentary environments are not yet fully understood. The effects of redox fluctuations may complicate one-to-one association of sedimentary Hg enrichments and massive volcanism at the Cambrian Series 2 – Series 3 boundary and elsewhere in the geologic record

Duality Invariant M-theory: Gauged supergravities and Scherk-Schwarz reductions

We consider the reduction of the duality invariant approach to M-theory by a U-duality group valued Scherk-Schwarz twist. The result is to produce potentials for gauged supergravities that are normally associated with non-geometric compactifications. The local symmetry reduces to gauge transformations with the gaugings exactly matching those of the embedding tensor approach to gauged supergravity. Importantly, this approach now includes a nontrivial dependence of the fields on the extra coordinates of the extended space.Comment: 22 pages Latex; v2: typos corrected and references adde

Inflation with Non-minimal Gravitational Couplings and Supergravity

We explore in the supergravity context the possibility that a Higgs scalar may drive inflation via a non-minimal coupling to gravity characterised by a large dimensionless coupling constant. We find that this scenario is not compatible with the MSSM, but that adding a singlet field (NMSSM, or a variant thereof) can very naturally give rise to slow-roll inflation. The inflaton is necessarily contained in the doublet Higgs sector and occurs in the D-flat direction of the two Higgs doublets.Comment: 13 pages, 1 figur

The impact of ocean acidification on the functional morphology of foraminifera

This work was supported by the NERC UK Ocean Acidification Research Programme grant NE/H017445/1. WENA acknowledges NERC support (NE/G018502/1). DMP received funding from the MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland). MASTS is funded by the Scottish Funding Council (grant reference HR09011) and contributing institutions.Culturing experiments were performed on sediment samples from the Ythan Estuary, N. E. Scotland, to assess the impacts of ocean acidification on test surface ornamentation in the benthic foraminifer Haynesina germanica. Specimens were cultured for 36 weeks at either 380, 750 or 1000 ppm atmospheric CO2. Analysis of the test surface using SEM imaging reveals sensitivity of functionally important ornamentation associated with feeding to changing seawater CO2 levels. Specimens incubated at high CO2 levels displayed evidence of shell dissolution, a significant reduction and deformation of ornamentation. It is clear that these calcifying organisms are likely to be vulnerable to ocean acidification. A reduction in functionally important ornamentation could lead to a reduction in feeding efficiency with consequent impacts on this organism’s survival and fitness.Publisher PDFPeer reviewe

Effects of steady state free precession parameters on cardiac mass, function, and volumes

G0400444/Medical Research Council/United Kingdom Wellcome Trust/United Kingdo

Inflammatory thresholds and the species-specific effects of colonising bacteria in stable chronic obstructive pulmonary disease

There has been increasing interest in the use of newer, culture-independent techniques to study the airway microbiome of COPD patients. We investigated the relationships between the three common potentially pathogenic microorganisms (PPMs) Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis, as detected by quantitative PCR (qPCR), and inflammation and health status in stable patients in the London COPD cohort

Assessment of potential cardiotoxic side effects of mitoxantrone in patients with multiple sclerosis

Previous studies showed that mitoxantrone can reduce disability progression in patients with multiple sclerosis (MS). There is, however, concern that it may cause irreversible cardiomyopathy with reduced left ventricular (LV) ejection fraction (EF) and congestive heart failure. The aim of this prospective study was to investigate cardiac side effects of mitoxantrone by repetitive cardiac monitoring in MS patients. The treatment protocol called for ten courses of a combined mitoxantrone (10 mg/m(2) body surface) and methylprednisolone therapy. Before each course, a transthoracic echocardiogram was performed to determine the LV end-diastolic diameter, the end-systolic diameter and the fractional shortening; the LV-EF was calculated. Seventy-three patients participated (32 males; age 48 +/- 12 years, range 20-75 years; 25 with primary progressive, 47 with secondary progressive and 1 with relapsing-remitting MS) who received at least four courses of mitoxantrone. Three of the 73 patients were excluded during the study (2 patients discontinued therapy; 1 patient with a previous history of ischemic heart disease developed atrial fibrillation after the second course of mitoxantrone). The mean cumulative dose of mitoxantrone was 114.0 +/- 33.8 mg. The mean follow-up time was 23.4 months (range 10-57 months). So far, there has been no significant change in any of the determined parameters (end-diastolic diameter, end-systolic diameter, fractional shortening, EF) over time during all follow-up investigations. Mitoxantrone did not cause signs of congestive heart failure in any of the patients. Further cardiac monitoring is, however, needed to determine the safety of mitoxantrone after longer follow-up times and at higher cumulative doses. Copyright (C) 2005 S. Karger AG, Basel