Self-investigation in adolescent chronic fatigue syndrome: Narrative changes and health improvement

Objective

A small-scale intervention study into narrative self-investigation in adolescent chronic fatigue syndrome (CFS).

Method

The self-confrontation method (SCM) is an instrument to assess and change personal life stories. Forty-two adolescents diagnosed with CFS were included and randomly assigned to either 6 or 12 sessions with the SCM. Twenty-five healthy adolescents were assigned to 6 sessions. Outcome was measured directly after the self-investigation procedure at 4 months. Follow-up measurements were made 10 months later. The Checklist Individual Strength and the Child Health Questionnaire were used to measure changes in fatigue, physical and psychosocial functioning.

Results

Self-investigation resulted in significant changes in participants’ narratives. Moreover, after self-investigation there was a significant improvement in fatigue, physical and psychosocial functioning for the adolescents with CFS. The patients who completed 12 sessions improved most. At follow-up, the positive effects were maintained.

Conclusion

Self-investigation enables a move beyond the symptoms of CFS in an individualized, patient centered way. Narrative transformation seems to contribute to improved physical and psychosocial outcome in adolescent CFS.

Practice implications

The SCM allows adolescents to discover (for themselves) factors that might cause or perpetuate their fatigue. The results suggest that self-investigation is a useful instrument in the management of adolescent CFS.     

Interactions of Shiga-like toxin with human peripheral blood monocytes

The cytotoxic effect of Shiga-like toxin (Stx; produced by certain Escherichia coli strains) plays a central role in typical hemolytic uremic syndrome (HUS). It damages the renal endothelium by inhibiting the cellular protein synthesis. Also, the monocyte has a specific receptor for Stx but is not sensitive for the cytotoxic effect. In this work, monocytes were studied as a potential transporter for Stx to the renal endothelium. Coincubation of isolated human monocytes loaded with Stx and target cells (vero cells and human umbilical vascular endothelial cells) were performed. Transfer was determined by measuring the protein synthesis of target cells and by flow cytometry. Furthermore, the effect of a temperature shift on loaded monocytes was investigated. Stx-loaded monocytes reduced the protein synthesis of target cells. After adding an antibody against Stx, incomplete recovery occurred. Also, adding only the supernatant of coincubation was followed by protein synthesis inhibition. Stx detached from its receptor on the monocyte after a change in temperature, and no release was detected without this temperature shift. Although the monocyte plays an important role in the pathogenesis of HUS, it has no role in the transfer of Stx.     

Vascular endothelial growth factor and blood-brain barrier disruption in tuberculous meningitis

BACKGROUND: Tuberculous meningitis (TBM) is characterized by disruption of the blood-brain barrier (BBB), cerebral edema and increased intracranial pressure (ICP). Vascular endothelial growth factor (VEGF) is a potent vascular permeability factor and a mediator of brain edema. AIMS: To investigate whether in children with TBM disruption of the BBB relates to VEGF production and to assess the effect of corticosteroids on Mycobacterium tuberculosis-induced VEGF production by mononuclear leukocytes. METHODS: Blood and CSF samples were collected from 26 children with stage 2-3 TBM and 20 controls. All patients received antituberculous and adjuvant corticosteroid therapy. Children were evaluated by ICP recording, computerized tomography scanning and outcome assessment at 6 months follow-up. BBB disruption was quantified by cerebrospinal fluid (CSF)-serum albumin ratios. VEGF concentrations were measured by enzyme-linked immunosorbent assay. In vitro human monocytic THP-1 cells were stimulated with M. tuberculosis sonicate or culture supernatant, and VEGF production was measured in the presence or absence of corticosteroids. RESULTS: CSF VEGF concentrations were significantly higher in TBM patients than in the controls and correlated with mononuclear cell counts (r = 0.64; P = 0.001) and CSF-serum albumin ratio (r = 0.49; P = 0.015). CSF VEGF did not significantly correlate with elevated ICP. In vitro induction of VEGF production by M. tuberculosis sonicate or culture supernatant could be completely abrogated by corticosteroid treatment. CONCLUSIONS: Inflammatory cells secrete VEGF during TBM. CSF VEGF correlates with BBB disruption. Inhibition of VEGF may explain part of the clinical effect of adjuvant corticosteroid therapy in TBM.     

Mid-dosing interval efavirenz plasma concentrations in HIV-1-infected children in Rwanda: treatment efficacy, tolerability, adherence, and the influence of CYP2B6 polymorphisms

This study evaluated mid-dosing interval efavirenz plasma concentrations and the influence of CYP2B6 polymorphisms in relation to efficacy, tolerability, and adherence in 97 Rwandan HIV-infected children (3-16 years). Plasma drug concentrations and CYP2B6 polymorphisms were determined. Ten children were excluded for nonadherence. Large intersubject variability in efavirenz plasma concentrations was found. Of the 87 remaining, efavirenz concentrations were therapeutic, supratherapeutic, and subtherapeutic in 67%, 20%, and 14%, respectively. No associations were found between efavirenz concentrations and central nervous system disturbances or virologic failure. Minor allele frequencies were 0.32 (516G>T), 0.33 (785A>G), and 0.09 (983T>C). Polymorphisms in CYP2B6 were strongly associated with high efavirenz levels.     

Contrast-enhanced MRI of murine myocardial infarction - part I

The use of contrast agents has added considerable value to the existing cardiac MRI toolbox that can be used to study murine myocardial infarction, as it enables detailed in vivo visualization of the molecular and cellular processes that occur in the infarcted and remote tissue. A variety of non-targeted and targeted contrast agents to study myocardial infarction are available and under development. Manganese, which acts as a calcium analogue, can be used to assess cell viability. Traditionally, low-molecular-weight Gd-containing contrast agents are employed to measure infarct size in a late gadolinium enhancement experiment. Gd-based blood-pool agents are used to study the vascular status of the myocardium. The use of targeted contrast agents facilitates more detailed imaging of pathophysiological processes in the acute and chronic infarct. Cell death was visualized by contrast agents functionalized with annexin A5 that binds specifically to phosphatidylserine accessible on dying cells and with an agent that binds to the exposed DNA of dead cells. Inflammation in the myocardium was depicted by contrast agents that target cell adhesion molecules expressed on activated endothelium, by contrast agents that are phagocytosed by inflammatory cells, and by using a probe that targets enzymes excreted by inflammatory cells. Cardiac remodeling processes were visualized with a contrast agent that binds to angiogenic vasculature and with an MR probe that specifically binds to collagen in the fibrotic myocardium. These recent advances in murine contrast-enhanced cardiac MRI have made a substantial contribution to the visualization of the pathophysiology of myocardial infarction, cardiac remodeling processes and the progression to heart failure, which helps to design new treatments. This review discusses the advances and challenges in the development and application of MRI contrast agents to study murine myocardial infarction.     

Three-dimensional T1 mapping of the mouse heart using variable flip angle steady-state MR imaging

Cardiac MR T(1) mapping is a promising quantitative imaging tool for the diagnosis and evaluation of cardiomyopathy. Here, we present a new preclinical cardiac MRI method enabling three-dimensional T(1) mapping of the mouse heart. The method is based on a variable flip angle analysis of steady-state MR imaging data. A retrospectively triggered three-dimensional FLASH (fast low-angle shot) sequence (3D IntraGate) enables a constant repetition time and maintains steady-state conditions. 3D T(1) mapping of the complete mouse heart could be achieved in 20 min. High-quality, bright-blood T(1) maps were obtained with homogeneous T(1) values (1764 ± 172 ms) throughout the myocardium. The repeatability coefficient of R(1) (1/T(1) ) in a specific region of the mouse heart was between 0.14 and 0.20 s(-1) , depending on the number of flip angles. The feasibility for detecting regional differences in ΔR(1) was shown with pre- and post-contrast T(1) mapping in mice with surgically induced myocardial infarction, for which ΔR(1) values up to 0.83 s(-1) were found in the infarct zone. The sequence was also investigated in black-blood mode, which, interestingly, showed a strong decrease in the apparent mean T(1) of healthy myocardium (905 ± 110 ms). This study shows that 3D T(1) mapping in the mouse heart is feasible and can be used to monitor regional changes in myocardial T(1), particularly in relation to pathology and in contrast-enhanced experiments to estimate local concentrations of (targeted) contrast agent.