Noninvasive determination of local wavespeed and distensibility of the femoral artery by comb-excited Fourier velocity-encoded magnetic resonance imaging: Measurements on athletic and nonathletic human subjects

Summary The local distensibility of arteries is of interest because distensibility varies from artery to artery, may be altered by disease to different extents in different arteries, and may be modified by physiological or pharmacological means. Using magnetic resonance imaging (MRI) we have measured local arterial wavespeed in the femoral artery in healthy human subjects and calculated local arterial distensibility. We acquired 2-D coronal and sagittal MR phase contrast angiograms of the femoral artery. We used a novel imaging technique, comb-excited Fourier velocity-encoded MRI, to obtain simultaneous measurements of arterial blood velocity at two stations 14cm apart on the femoral artery. The separation of the two stations divided by the delay between the onset of forward flow at the two stations was used to calculate the wavespeed. The measurements were made on 16 healthy men (8 athletes, 8 non-athletes) in the age range 20–30 years, who were scanned with the use of ECG gating and an extremity coil in a 1.5 Tesla scanner (GE Medical Systems, Milwaukee, WI). By systematically altering the delay between the R-wave and data acquisition, a temporal resolution of 2–4ms was achieved. The onset of forward flow at each station was determined from a least-squares fit to the data for 30% of the maximum velocity during the cardiac cycle. Average femoral artery wavespeed was 7.7m/s ± 1.2 in the athletes and 11.5m/s ± 1.1 in the non-athletes (P < 0.001). The corresponding arterial distensibility values were 1.87 ± 0.86 × 10^–5kg^–1 s²m and 7.72 ± 1.63 × 10^–6kg^–1 s²m (P < 0.001). In most of the subjects there was transient flow reversal in the femoral artery immediately preceding the onset of forward flow. This helped in the identification of the onset of forward flow and hence the determination of arterial wavespeed.     

Complexity and reflexivity: two important issues for economic evaluation in health care

Economic evaluations are analytic techniques to assess the relative costs and consequences of health care programmes and technologies. Their role is to provide rigorous data to inform the health care decision-making process. Economic evaluation may oversimplify complex health care decisions. These analyses often ignore important health consequences, contextual elements, relationships or other relevant modifying factors, which might not be appropriate in a multi-objective, multi-stakeholder issue. One solution would be to develop a new paradigm based on the issues of perspective and context. Complexity theory may provide a useful conceptual framework for economic evaluation in health care. Complexity thinking develops an awareness of issues including uncertainty, contextual issues, multiple perspectives, broader societal involvement, and transdisciplinarity. This points the economic evaluation field towards an accountability and epistemology based on pluralism and uncertainty, requiring new forms of lay-expert engagement and roles of lay knowledge into decision-making processes. This highlights the issue of reflexivity in economic evaluation in health care. A reflexive approach would allow economic evaluators to analyze how objective structures and subjective elements influence their practices. In return, this would point increase the integrity and reliability of economic evaluations. Reflexivity provides opportunities for critically thinking about the organization and activities of the intellectual field, and perhaps the potential of moving in new, creative directions. This paper argues for economic evaluators to have a less positivist attitude towards what is useful knowledge, and to use more imagination about the data and methodologies they use.     

Self expandable stents for relief of venous baffle obstruction after the Mustard operation

Objective—Obstruction of the venous pathways after Mustard repair for transposition of the great arteries is associated with an increased risk of arrhythmia and sudden death. The purpose of this study was to assess the effectiveness of the largest (tracheal 22 × 40 mm) Wallstents in treating baffle obstructions.
Design—Retrospective analysis of patients with stented venous pathways.
Subjects—Eleven patients with baffle obstruction after Mustard repair for transposition of the great arteries.
Interventions—Stenoses were dilated with an 18 or 20 mm balloon. However, recoil was noticed in 11 patients: immediately (n = 7) or on repeat angiography (n = 4). Eighteen stents were implanted (mean (SD)) 18 (3.3) years postoperatively. After dilatation a tracheal Wallstent (11.5 F) was deployed.
Main outcome measures—Relief of obstruction, haemodynamic improvement.
Results—In the inferior vena cava, 10 stents were deployed in seven baffle obstructions with an increase in diameter from 9.8 (2.4) mm to 16.5 (1.4) mm (p < 0.01) and a mean (SD) pressure gradient decrease from 5.1 (3.6) mm Hg to 1.4 (2.0) mm Hg; in the superior vena cava, eight stents were implanted increasing the diameter from 9.1 (3.7) mm to 15.6 (3.8) mm (p < 0.001) with a decrease in mean pressure gradient from 5.1 (2.7) mm Hg to 1.9 (1.5) mm Hg. No complications were experienced during implantation. No anticoagulation was prescribed. During follow up (1.7 (0.6) years; range, 0.9-2.6) no problems were noted; five patients were re-catheterised without change in measurements. There was no evidence of peal formation in any of the stents.
Conclusion—It is concluded that Wallstents are safe, easy to use, and effective in relieving baffle obstruction. Anticoagulation does not seem neccessary.

Keywords: Mustard procedure;  venous baffle obstruction;  stent     

In vitro aggregating β-lactamase-polyQ chimeras do not induce toxic effects in an in vivo <Emphasis Type="Italic">Caenorhabditis elegans</Emphasis> model

Background

A series of human diseases are caused by the misfolding and aggregation of specific proteins or peptides into amyloid fibrils; nine of these diseases, referred to as polyglutamine diseases, are associated with proteins carrying an expanded polyglutamine (polyQ) region. While the presence of this latter is thought to be the determinant factor for the development of polyQ diseases, the non-polyQ regions of the host proteins are thought to play a significant modulating role.

Method

In order to better understand the role of non-polyQ regions, the toxic effects of model proteins bearing different polyQ regions (containing up to 79 residues) embedded at two distinct locations within the β-lactamase (BlaP) host enzyme were evaluated in Caenorhabditis elegans. This small organism can be advantageous for the validation of in vitro findings, as it provides a multicellular context yet avoids the typical complexity of common studies relying on vertebrate models. Several phenotypic assays were performed in order to screen for potential toxic effects of the different BlaP-polyQ proteins.

Results

Despite the significant in vitro aggregation of BlaP-polyQ proteins with long polyQ regions, none of the BlaP-polyQ chimeras aggregated in the generated transgenic in vivo models.

Conclusion

The absence of a toxic effect of the expression of BlaP-polyQ chimeras may find its cause in biochemical mechanisms present in vivo to cope with protein aggregation (e.g. presence of chaperones) or in C. elegans’ limitations such as its short lifespan. It is plausible that the aggregation propensities of the different BlaP chimeras containing embedded polyQ sequences are too low in this in vivo environment to permit their aggregation. These experiments emphasize the need for several comparative and in vivo verification studies of biologically relevant in vitro findings, which reveal both the strengths and limitations of widely used model systems.

     

A novel acoustically quiet coil for neonatal MRI system

Magnetic resonance imaging (MRI) acoustic exposure has the potential to elicit physiological distress and impact development in preterm and term infants. To mitigate this risk, a novel acoustically quiet coil was developed to reduce the sound pressure level experienced by neonates during MR procedures. The new coil has a conventional high‐pass birdcage radio frequency design, but is built on a framework of sound abating material. We evaluated the acoustic and MR imaging performance of the quiet coil and a conventional body coil on two small footprint neonatal intensive care unit MRI systems. Sound pressure level and frequency response measurements were made for six standard clinical MR imaging protocols. The average sound pressure level, reported for all six imaging pulse sequences, was 82.2 dBA for the acoustically quiet coil, and 91.1 dBA for the conventional body coil. The sound pressure level values measured for the acoustically quiet coil were consistently lower, 9 dBA (range 6–10 dBA) quieter on average. The acoustic frequency response of the two coils showed a similar harmonic profile for all imaging sequences. However, the amplitude was lower for the quiet coil, by as much as 20 dBA. © 2015 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 45B: 107–114, 2015     

BK polyomavirus-associated hemorrhagic cystitis among pediatric allogeneic bone marrow transplant recipients: Treatment response and evidence for nosocomial transmission

BackgroundBK polyomavirus-associated hemorrhagic cystitis (BK-PyVHC) is a significant complication of allogenic hematopoietic stem cell transplantation (HSCT), but risk factors and treatment are currently unresolved. BK-PyVHC typically presents with clinical cystitis, macrohematuria, and increasing urine and blood BKV loads.ObjectivesCharacterization of children undergoing allogeneic HSCT with BK-PyVHC and their clinical and antibody response to cidofovir treatment.Study designBy prospective screening of urine and plasma in 50 pediatric allogenic HSCT performed between 2008 and 2010, we identified 6 (12%) children with BK-PyVHC. Cidofovir was administered intravenously to 5 patients and intravesically to 4 patients (3 double treatments).ResultsDecreasing BKV viremia of > 2 log₁₀ copies/mL and clinical resolution was seen in 4 patients over 5–12 weeks. Responses occurred only in patients mounting BKV-specific IgM and IgG responses. Epidemic curve plots, BKV genotyping and contact tracing provided evidence of transmission between 2 BKV-seronegative patients, but ruled out transmission among the remaining four patientsConclusionsThe data suggest that BK-PyVHC may be the result of nosocomial transmission in children with low/undetectable BKV antibodies and raises urgent questions about appropriate infection control measures and the role of cidofovir.     

Inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) expression in fulminant hepatic failure

BACKGROUND/AIMS: Inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) have important functions in inflammation and vasoregulation but their role in fulminant hepatic failure (FHF) is not well understood. METHODS: Intrahepatic in situ staining and semi-quantification of iNOS and eNOS by immunohistochemistry in 25 patients with FHF, in 40 patients with chronic liver diseases (CLD) and in ten normal controls (NC). RESULTS: Expression patterns of iNOS and eNOS differed. While in NC only faint iNOS expression was found in some Kupffer cells/macrophages and hepatocytes, eNOS was expressed constitutively in sinusoidal and vascular endothelial cells. In CLD, iNOS expression was induced in Kupffer cells/macrophages and hepatocytes, representing the main iNOS expressing cell types. Additionally, bile ducts, vascular endothelial cells and lymphocytes also expressed iNOS (P = 0.001). In contrast, no differences were found between eNOS expression in CLD and NC (P = 0.64). The same cell types expressed eNOS and iNOS in FHF but numbers of both were significantly enhanced, exceeding the levels seen in CLD (P < 0.001, P = 0.017). CONCLUSIONS: Our data demonstrate that iNOS and eNOS are differently regulated in physiologic conditions and in liver disease. While eNOS seems to be involved in the physiological regulation of hepatic perfusion, strong upregulation of iNOS might contribute to inflammatory processes in FHF.