Signs and symptoms in children with a serious infection: a qualitative study

BACKGROUND: Early diagnosis of serious infections in children is difficult in general practice, as incidence is low, patients present themselves at an early stage of the disease and diagnostic tools are limited to signs and symptoms from observation, clinical history and physical examination. Little is known which signs and symptoms are important in general practice. With this qualitative study, we aimed to identify possible new important diagnostic variables. METHODS: Semi-structured interviews with parents and physicians of children with a serious infection. We investigated all signs and symptoms that were related to or preceded the diagnosis. The analysis was done according to the grounded theory approach. Participants were recruited in general practice and at the hospital. RESULTS: 18 children who were hospitalised because of a serious infection were included. On average, parents and paediatricians were interviewed 3 days after admittance of the child to hospital, general practitioners between 5 and 8 days after the initial contact. The most prominent diagnostic signs in seriously ill children were changed behaviour, crying characteristics and the parents' opinion. Children either behaved drowsy or irritable and cried differently, either moaning or an inconsolable, loud crying. The parents found this illness different from previous illnesses, because of the seriousness or duration of the symptoms, or the occurrence of a critical incident. Classical signs, like high fever, petechiae or abnormalities at auscultation were helpful for the diagnosis when they were present, but not helpful when they were absent. CONCLUSION: behavioural signs and symptoms were very prominent in children with a serious infection. They will be further assessed for diagnostic accuracy in a subsequent, quantitative diagnostic study

Modified constraint-induced movement therapy or bimanual occupational therapy following injection of Botulinum toxin-A to improve bimanual performance in young children with hemiplegic cerebral palsy: a randomised controlled trial methods paper

<p>Abstract</p> <p>Background</p> <p>Use of Botulinum toxin-A (BoNT-A) for treatment of upper limb spasticity in children with cerebral palsy has become routine clinical practice in many paediatric treatment centres worldwide. There is now high-level evidence that upper limb BoNT-A injection, in combination with occupational therapy, improves outcomes in children with cerebral palsy at both the body function/structure and activity level domains of the International Classification of Functioning, Disability and Health. Investigation is now required to establish what amount and specific type of occupational therapy will further enhance functional outcomes and prolong the beneficial effects of BoNT-A.</p> <p>Methods/Design</p> <p>A randomised, controlled, evaluator blinded, prospective parallel-group trial. Eligible participants were children aged 18 months to 6 years, diagnosed with spastic hemiplegic cerebral palsy and who were able to demonstrate selective motor control of the affected upper limb. Both groups received upper limb injections of BoNT-A. Children were randomised to either the modified constraint-induced movement therapy group (experimental) or bimanual occupational therapy group (control). Outcome assessments were undertaken at pre-injection and 1, 3 and 6 months following injection of BoNT-A. The primary outcome measure was the Assisting Hand Assessment. Secondary outcomes included: the Quality of Upper Extremity Skills Test; Pediatric Evaluation of Disability Inventory; Canadian Occupational Performance Measure; Goal Attainment Scaling; Pediatric Motor Activity Log; modified Ashworth Scale and; the modified Tardieu Scale.</p> <p>Discussion</p> <p>The aim of this paper is to describe the methodology of a randomised controlled trial comparing the effects of modified constraint-induced movement therapy (a uni-manual therapy) versus bimanual occupational therapy (a bimanual therapy) on improving bimanual upper limb performance of children with hemiplegic cerebral palsy following upper limb injection of BoNT-A. The paper outlines the background to the study, the study hypotheses, outcome measures and trial methodology. It also provides a comprehensive description of the interventions provided.</p> <p>Trial Registration</p> <p>ACTRN12605000002684</p

Sphingosine-1-Phosphate and Macrophage Biology - How the Sphinx Tames the Big Eater

The sphingolipid sphingosine-1-phosphate (S1P) is produced by sphingosine kinases to either signal through intracellular targets or to activate a family of specific G-protein-coupled receptors (S1PR). S1P levels are usually low in peripheral tissues compared to the vasculature, forming a gradient that mediates lymphocyte trafficking. However, S1P levels rise during inflammation in peripheral tissues, thereby affecting resident or recruited immune cells, including macrophages. As macrophages orchestrate initiation and resolution of inflammation, the sphingosine kinase/S1P/S1P-receptor axis emerges as an important determinant of macrophage function in the pathogenesis of inflammatory diseases such as cancer, atherosclerosis, and infection. In this review, we therefore summarize the current knowledge how S1P affects macrophage biology

Chronic Hypoxia Enhances β-Oxidation-Dependent Electron Transport via Electron Transferring Flavoproteins

Hypoxia poses a stress to cells and decreases mitochondrial respiration, in part by electron transport chain (ETC) complex reorganization. While metabolism under acute hypoxia is well characterized, alterations under chronic hypoxia largely remain unexplored. We followed oxygen consumption rates in THP-1 monocytes during acute (16 h) and chronic (72 h) hypoxia, compared to normoxia, to analyze the electron flows associated with glycolysis, glutamine, and fatty acid oxidation. Oxygen consumption under acute hypoxia predominantly demanded pyruvate, while under chronic hypoxia, fatty acid- and glutamine-oxidation dominated. Chronic hypoxia also elevated electron-transferring flavoproteins (ETF), and the knockdown of ETF&#8315;ubiquinone oxidoreductase lowered mitochondrial respiration under chronic hypoxia. Metabolomics revealed an increase in citrate under chronic hypoxia, which implied glutamine processing to &#945;-ketoglutarate and citrate. Expression regulation of enzymes involved in this metabolic shunting corroborated this assumption. Moreover, the expression of acetyl-CoA carboxylase 1 increased, thus pointing to fatty acid synthesis under chronic hypoxia. Cells lacking complex I, which experienced a markedly impaired respiration under normoxia, also shifted their metabolism to fatty acid-dependent synthesis and usage. Taken together, we provide evidence that chronic hypoxia fuels the ETC via ETFs, increasing fatty acid production and consumption via the glutamine-citrate-fatty acid axis

4f-conduction electron hybridization in ternary CeTMAl compounds

We present an investigation of Ce-TM-Al phase diagrams with TM = Ru, Pd, Pt and Au. Several new compounds have been characterized by measurements of the electrical resistivity rho(T), the dc susceptibility chi(T) and, in some cases, the specific heat C(T). We find that in the compounds with TM=Ru, the hybridization strength between 4f and conduction electrons is strong, leading in most compounds to an intermediate valent (IV) state. By contrast, most of the investigated compounds with TM = Pd, Pt and Au order magnetically indicating a much weaker hybridization strength. However, some of the Pt and especially Pd compounds are very near to the crossover from the magnetic to the non-magnetic regime as deduced from a Kondo-type maximum in the resistivity and a large electronic specific heat at low temperatures