Accuracy and repeatability of fourier velocity encoded M‐mode and two‐dimensional cine phase contrast for pulse wave velocity measurement in the descending aorta

Purpose:

To assess the accuracy and repeatability of Fourier velocity encoded (FVE) M‐mode and two‐dimensional (2D) phase contrast with through‐plane velocity encoding (2D‐PC) for pulse wave velocity (PWV) evaluation in the descending aorta using five different analysis techniques.

Materials and Methods:

Accuracy experiments were conducted on a tubular human‐tissue‐mimicking phantom integrated into a flow simulator. The theoretical PWV value was derived from the Moens‐Korteweg equation after measurement of the tube elastic modulus by uniaxial tensile testing (PWV = 6.6 ± 0.7 m/s). Repeatability was assessed on 20 healthy volunteers undergoing three consecutive MR examinations.

Results:

FVE M‐mode PWV was more repeatable than 2D‐PC PWV independently of the analysis technique used. The early systolic fit (ESF) method, followed by the maximum of the first derivative (1st der.) method, was the most accurate (PWV = 6.8 ± 0.4 m/s and PWV = 7.0 ± 0.6 m/s, respectively) and repeatable (inter‐scan within‐subject variation δ = 0.096 and δ = 0.107, respectively) for FVE M‐mode. For 2D‐PC, the 1st der. method performed best in terms of accuracy (PWV = 6.8 ± 1.1 m/s), whereas the ESF algorithm was the most repeatable (δ = 0.386).

Conclusion:

FVE M‐mode allows rapid, accurate and repeatable central PWV evaluation when the ESF algorithm is used. 2D‐PC requires long scan times and can provide accurate although much less repeatable PWV measurements when the 1st der. method is used. J. Magn. Reson. Imaging 2010;31:1185–1194. © 2010 Wiley‐Liss, Inc.     

Controversies in the management of bacterial meningitis

Bacterial meningitis is an important infection of childhood with significant morbidity and mortality, and clinicians are faced with controversies over steroid use and fluid restriction in its initial management because the standard of practice is not clear. A 1999 survey of paediatric infectious diseases specialists demonstrated that only 56% of respondents recommended dexamethasone for Haemophilus influenzae type b meningitis and only 34% recommended dexamethasone for Streptococcus pneumoniae meningitis, despite recommendations for dexamethasone in the 1997 Red Book. The present article illustrates a typical case presentation of bacterial meningitis, and discusses dexamethasone use and fluid restriction. The use of intravenous fluid therapy is also reviewed, based on results from the single prospective randomized clinical trial in this area.     

Sequencing and Functional Analysis of the SNRPN Promoter: In Vitro Methylation Abolishes Promoter Activity

The gene encoding the small nuclear ribonucleoprotein-associated polypeptide N (SNRPN) maps to the Prader–Willi syndrome critical region on chromosome 15 and is expressed preferentially from the paternal allele. A CpG island encompassing the first exon of SNRPN is methylated on the inactive maternal allele. DNA sequence was determined for a cosmid containing the first three exons of SNRPN and extending 20 kb upstream and 15 kb downstream from the CpG island. This region is extremely rich in Alu elements and other repetitive sequences and contains a single CpG island, which includes numerous short direct repeat sequences. Functional analysis of the first exon revealed strong promoter activity for a 260-bp fragment extending 207 bp upstream from the exon. In vitro methylation of this 260-bp fragment abolished promoter activity completely, suggesting that the silencing of the maternal SNRPN allele may be a direct consequence of methylation of the promoter region.     

Neutralizing antibodies in patients with chronic hepatitis C infection treated with (Peg)-interferon/ribavirin.

BACKGROUND: The role of neutralizing antibody (NAb) in determining response to antiviral therapy has not been established. OBJECTIVE: In this study we have analysed the kinetic's of the NAb response in patients with chronic hepatitis C who received antiviral therapy. STUDY DESIGN: Seventeen patients infected with genotype 1, 2a/c or 3a hepatitis C virus (HCV) were enrolled, eight with a sustained virological response (SVR), five non-responders and four relapsers. RESULTS: The mean NAb titre required to neutralize 50% of the E1E2-pp in patients who achieved an SVR (294+/-S.D. 51), in relapsers (246+/-S.D. 61.7) and non-responders (286+/-S.D. 80.95) did not differ significantly between the patient groups and did not alter during the course of treatment (P>0.01). Genetic variation present before antiviral therapy was analysed by single strand conformation polymorphism (SSCP) and failed to demonstrate a significant difference in the mean number of amplified E1E2 DNA fragments from the serum of patients who achieved an SVR (3.15+/-S.D. 1.53), relapsers (2.8+/-S.D. 1.32) or non-responders (3.69+/-S.D. 1.75). The baseline serum HCV viral loads were also not significantly different between patients who achieved an SVR (1.4 x 10(6) copies/ml; +/-S.D. 2.4 x 10(6)), relapsers (1.3 x 10(7) copies/ml; +/-S.D. 2.4 x 10(7)) and non-responders (1.5 x 10(6) copies/ml; +/-S.D. 1.1 x 10(6)). CONCLUSION: We have shown that neutralizing anti-HCVpp antibody is not associated with response to antiviral therapy. In addition, there was no correlation between baseline virological load, circulating viral quasi-species, NAb titres and final response to treatment.     

The microRNA‐9/B‐lymphocyte‐induced maturation protein‐1/IL‐2 axis is differentially regulated in progressive HIV infection

The fine control of T‐cell differentiation and its impact on HIV disease states is poorly understood. In this study, we demonstrate that B‐lymphocyte‐induced maturation protein‐1 (Blimp‐1/Prdm1) is highly expressed in CD4⁺ T cells from chronically HIV‐infected (CHI) patients compared to cells from long‐term nonprogressors or healthy controls. Stimulation through the T‐cell receptor in the presence ofIL‐2 induces Blimp‐1 protein expression. We show here that Blimp‐1 levels are translationally regulated by microRNA‐9 (miR‐9). Overexpression of miR‐9 induces Blimp‐1 repression, restoring IL‐2 secretion in CD4⁺ T cells via reduction in the binding of Blimp‐1 to the il‐2 promoter. In CHI patients where IL‐2 expression is reduced and there is generalized T‐cell dysfunction, we show differential expression of both miR‐9 and Blimp‐1 in CD4⁺ cells compared with levels in long‐term nonprogressors. These data identify a novel miR‐9/Blimp‐1/IL‐2 axis that is dysregulated in progressive HIV infection.     

Assessing depression severity using the UK Quality and Outcomes Framework depression indicators: a systematic review

BackgroundDepression is a major cause of chronic ill-health and is managed in primary care. Indicators on depression severity assessment were introduced into the UK Quality and Outcomes Framework (QOF) in 2006 and 2009. QOF is a pay-for-performance scheme and indicators should have evidence to support their use; potential unintended consequences should also have been considered.AimTo review the effectiveness of routine assessment of depression severity using structured tools in primary care, and to determine the views of GPs and patients regarding their use.DesignSystematic review.MethodStudies were identified by searching electronic databases; study selection, data abstraction, and quality assessment were carried out by one reviewer, with checks from other authors and GRADE (grading of recommendations, assessment, development and evaluation) tables completed for included effectiveness studies.ResultsEight studies met the eligibility criteria. There was very low-quality evidence that assessing severity in a structured way at diagnosis using a validated tool led to interventions that were appropriate to the severity of depression. Patients and GPs had different perceptions of the assessment of depression at diagnosis, with patients being more positive. GPs highlighted unintended consequences. There was low-quality evidence that structured assessment at follow-up led to increased rates of remission and response, but changes to management were not seen. Patients used this assessment to measure their own response to treatment.ConclusionAny estimate of the effect of structured assessment of depression severity in UK general practice is uncertain. GPs consider routine use of questionnaires as incentivised by the QOF has unintended consequences, which could adversely affect patient care.     

Strategies for success: a toolbox of coping strategies used by breastfeeding women

Aims. The purpose of this paper is to present the findings of two qualitative studies which identified strategies used by breastfeeding women to assist them to continue breastfeeding. Background. While breastfeeding initiation rates are high in Australia, the majority of women wean before the recommended time. The identification of interventions which may increase breastfeeding duration is therefore a research priority. Design. The Against All Odds study used a case‐controlled design to investigate the characteristics of women who continued to breastfeed in the face of extraordinary difficulties. Phase One of the I Think I Can study employed the Nominal Group Technique to investigate the views of subject matter experts regarding which psychological factors may influence the duration of breastfeeding. Method. Against All Odds study participants (n = 40) undertook a one‐ to two‐hour interview and the transcribed data were analysed using thematic analysis. Stratified purposeful sampling was employed in the I Think I Can study (n = 21), with participants assigned group membership according to their most recent breastfeeding experience. A fourth group was composed of experienced breastfeeding clinicians. The nominal group technique was used to generate group data and segments of the discussion were audiotaped and transcribed for thematic analysis. Results. Participants in both the studies raised strategies used to assist them in their efforts to cope with the challenges of breastfeeding and early motherhood. These strategies included increasing breastfeeding knowledge, staying relaxed and ‘looking after yourself’, the use of positive self‐talk, challenging unhelpful beliefs, problem solving, goal setting and the practice of mindfulness. Conclusions. Employment of these simple behavioural and cognitive strategies may assist women to cope with the pressures inherent in the experience of early mothering, thereby increasing the duration of breastfeeding. Relevance to clinical practice. These results may represent a ‘tool box’ of coping strategies which can be provided to women for use in the postnatal period.