Quantifying the intra- and extravascular contributions to spin-echo fMRI at 3 T.

Functional MRI (fMRI) by means of spin-echo (SE) techniques provides an interesting alternative to gradient-echo methods because the contrast is based primarily on dynamic averaging associated with the blood oxygenation level-dependent (BOLD) effect. In this article the contributions from different brain compartments to BOLD signal changes in SE echo planar imaging (EPI) are investigated. To gain a better understanding of the underlying mechanisms that cause the fMRI contrast, two experiments are presented: First, the intravascular contribution is decomposed into two fractions with different regimes of flow by means of diffusion-weighting gradient schemes which are either flow-compensated, or will maximally dephase moving spins. Second, contributions from the intra- and extravascular space are selectively suppressed by combining flow-weighting with additional refocusing pulses. The results indicate two qualitatively different components of flowing blood which contribute to the BOLD contrast and a nearly equal share in functional signal from the intra- and extravascular compartments at TE approximately 80 ms and 3 T. Combining these results, there is evidence that at least one-half of the functional signal originates from the parenchyma in SE fMRI at 3 T. The authors suggest the use of flow-compensated diffusion weighting for SE fMRI to improve the sensitivity to the parenchyma.     

Risk factors for Epstein–Barr virus reactivation after renal transplantation: Results of a large,multi-centre study

Epstein–Barr virus (EBV) reactivation is a very common and potentially lethal complication of renal transplantation. However, its risk factors and effects on transplant outcome are not well known. Here, we have analysed a large, multi-centre cohort (N = 512) in which 18.4% of the patients experienced EBV reactivation during the first post-transplant year. The patients were characterized pre-transplant and two weeks post-transplant by a multi-level biomarker panel. EBV reactivation was episodic for most patients, only 12 patients showed prolonged viraemia for over four months. Pre-transplant EBV shedding and male sex were associated with significantly increased incidence of post-transplant EBV reactivation. Importantly, we also identified a significant association of post-transplant EBV with acute rejection and with decreased haemoglobin levels. No further severe complications associated with EBV, either episodic or chronic, could be detected. Our data suggest that despite relatively frequent EBV reactivation, it had no association with serious complications during the first post-transplantation year. EBV shedding prior to transplantation could be employed as biomarkers for personalized immunosuppressive therapy. In summary, our results support the employed immunosuppressive regimes as relatively safe with regard to EBV. However, long-term studies are paramount to support these conclusions.     

INTENSIVE CHEMOTHERAPEUTIC REGIMENS AGAINST ACUTE LEUKEMIA TRANSIENTLY SUPPRESS ASTHMA SYMPTOMS BUT DO NOT LEAD TO LONG-TERM RELIEF

In some very rare cases children suffer from a combination of asthma and a malignant disease. This study investigated whether intensive chemotherapy might have a positive effect on asthma in these special cases and whether asthma generally relapses after completion of chemotherapy. The authors monitored clinical outcome and lung function of 43 children with acute lymphoblastic leukemia and non-Hodgkin lymphoma who received chemotherapy at the University Children's Hospital of Greifswald between 1993 and 1998. Cytostatic chemotherapy was administered according to the German treatment protocols. Two of the 43 patients had asthma before leukemia was diagnosed. During the course of chemotherapy, asthma symptoms diminished promptly after beginning of chemotherapy but asthma was rediagnosed after completion of chemotherapy in both cases. The third patient developed asthmatic symptoms shortly after completion of chemotherapy for the first time. It can be stated that chemotherapy does not essentially cure asthma. Therefore, it seems mandatory to perform follow-up lung testings after chemotherapy, especially in patients with asthma.     

The strength of primary care in Europe: an international comparative study

Background

A suitable definition of primary care to capture the variety of prevailing international organisation and service-delivery models is lacking.

Aim

Evaluation of strength of primary care in Europe.

Design and setting

International comparative cross-sectional study performed in 2009–2010, involving 27 EU member states, plus Iceland, Norway, Switzerland, and Turkey.

Method

Outcome measures covered three dimensions of primary care structure: primary care governance, economic conditions of primary care, and primary care workforce development; and four dimensions of primary care service-delivery process: accessibility, comprehensiveness, continuity, and coordination of primary care. The primary care dimensions were operationalised by a total of 77 indicators for which data were collected in 31 countries. Data sources included national and international literature, governmental publications, statistical databases, and experts’ consultations.

Results

Countries with relatively strong primary care are Belgium, Denmark, Estonia, Finland, Lithuania, the Netherlands, Portugal, Slovenia, Spain, and the UK. Countries either have many primary care policies and regulations in place, combined with good financial coverage and resources, and adequate primary care workforce conditions, or have consistently only few of these primary care structures in place. There is no correlation between the access, continuity, coordination, and comprehensiveness of primary care of countries.

Conclusion

Variation is shown in the strength of primary care across Europe, indicating a discrepancy in the responsibility given to primary care in national and international policy initiatives and the needed investments in primary care to solve, for example, future shortages of workforce. Countries are consistent in their primary care focus on all important structure dimensions. Countries need to improve their primary care information infrastructure to facilitate primary care performance management.     

Dual echo EPI – The method of choice for fMRI in the presence of magnetic field inhomogeneities?

FMRI studies of the orbitofrontal cortex or the inferior temporal lobes are often compromised by susceptibility artefacts, which may result in signal reduction or loss in gradient echo (GE) EPI. Spin echo (SE) EPI is considerably more robust against susceptibility-related signal loss, but its intrinsic sensitivity to changes in the blood oxygenation level dependent (BOLD) contrast is generally lower. In this study, we performed a direct comparison of GE and SE fMRI using a single-shot dual echo EPI acquisition scheme. Transient hypercapnia, induced by breathing Carbogen (5% CO₂, 95% O₂), was used as a global physiological stimulus to alter the BOLD contrast. In regions affected by magnetic field inhomogeneities, SE EPI provided significantly higher BOLD sensitivity than GE EPI. Such regions included the orbitofrontal cortex, temporal pole, anterior inferior temporal cortex, as well as parts of the lateral inferior temporal cortex and the lateral cerebellum. Dual echo fMRI benefits from the robustness of SE EPI in these critical regions while utilising the generally higher sensitivity of GE EPI in normal regions. It therefore provides an attractive solution for fMRI studies that require optimum sensitivity in both normal and critical brain regions. Furthermore, a general method is proposed to combine the GE and SE data into a single hybrid data set that provides optimum sensitivity in the whole brain. This method can be applied to any experimental design that can be expressed in terms of a generalised linear model. The feasibility of this approach is demonstrated both theoretically and experimentally.     

Antibiotic sequential therapy for febrile neutropenia in pediatric patients with malignancy

Children suffering malignant diseases can experience phases of bone marrow depression during intensive chemotherapy. The influence of antibiotic sequence therapy on the course of diseases was examined in 41 pediatric patients with malignant diseases. Inclusion criteria were neutropenia (ANC < 500/microL), rectal body temperature over 38.5 degrees C, and increased C-reactive protein (CRP, cutoff > 5.0 mg/L). The first stage of therapy comprised the following antibiotics: piperacillin, teicoplanin, and gentamicin. In stage 2 imipenem, teicoplanin, and tobramycin were administered. Fluconazole was the antifungal drug of choice in stages 1 and 2. In the first level of antibiotic therapy 68% of the patients showed a positive reaction. The C-reactive protein was a sensitive parameter, which significantly decreased with 3 days of therapy. A total of 72% of the bacteriological smears were sterile. All patients survived the septic phase.