Standardisierte Kontrastmittelsonographie (CEUS) in der klinischen Akut- und Notfallmedizin sowie Intensivmedizin (CEUS-Akut)

Die Anaesthesiologie -     

Meningeal cells influence cerebellar development over a critical period

Summary We have investigated the influence of meningeal cells on the development of the cerebellum by destroying these cells with 6-hydroxydopamine in hamsters of different ages. The ensuing foliation and lamination disruption in the cerebellar vermis is attributed to a disintegration of the cerebellar surface and a disorganization of the glial scaf-fold of the cerebellar cortex due to a loss of meningeal-glial interaction in stabilizing the extracellular matrix at the glia limitans superficialis (v. Knebel Doeberitz et al. 1986, Neuroscience 17:409–426). The severity of these cerebellar defects is correlated with the ontogenetic stage at which meningeal cells are destroyed, being greatest after treatment at postnatal day 1 and decreasing thereafter until day 5 and beyond, when no abnormalities occur, although all meningeal cells are destroyed throughout. The absence of cerebellar defects after destruction of meningeal cells at day 5 or later is associated firstly with the end of the period of branching morphogenesis of the cerebellum when all folial primordia are established, and, secondly, with the maturation of the glia limitans superficialis. These findings indicate that meningeal cells stabilize the cerebellar surface and glial scaffold over a critical period that ends, when the pattern of cerebellar foliation is established, and when the glia limitans superficialis has reached a mature state. Beyond this stage glial end-feet alone are sufficient to maintain the epithelial integrity of the cerebellum.     

Reliable high risk HPV DNA testing by polymerase chain reaction: an intermethod and intramethod comparison

BACKGROUND: The development of a reproducible, sensitive, and standardised human papillomavirus (HPV) polymerase chain reaction (PCR) test is required to implement HPV testing in cervical cancer screening programmes and for triaging women with mild to moderate dysplasia. AIMS: To determine the intermethod agreement between different GP5+/6+ and MY09/11 PCR based protocols for the detection and typing of high risk (HR) HPV DNA in cervical smears and to assess the intramethod reproducibility of the GP5+/6+ PCR enzyme immunoassay (EIA) for HR-HPV detection. METHODS: For the intermethod comparison, crude aliquots of 20 well characterised cervical smears comprising five HPV negative samples, and six and nine samples containing single and multiple HPV infections, respectively, were coded and sent from reference laboratory (A) to three other laboratories. One of these (laboratory B) used the GP5+/6+ PCR-EIA and was provided with standard protocols. Another laboratory (C) used GP5+/6+ PCR combined with sequence analysis and type specific PCR, whereas two laboratories (D and E) used MY09/11 PCR followed by restriction fragment length polymorphism (RFLP) analysis for the detection and typing of HR-HPV. The intramethod agreement of GP5+/6+ PCR-EIA was analysed in a subsequent study with four other laboratories (F to I) on crude aliquots of 50 well characterised cervical smears, consisting of 32 HR-HPV positive and 18 HPV negative samples. Standardised protocols, primers, and probes were also provided by the reference laboratory for HR-HPV detection. RESULTS: In the intermethod comparison, pairwise agreement of the different laboratories with reference laboratory A for the detection of HR-HPV varied between 75% and 100% (kappa values: 0.5 to 1). Typing data revealed a broader range in pairwise agreement rates between 32% and 100%. The highest agreement was found between laboratories A and B using standardised protocols and validated reagents. In the intramethod evaluation, pairwise comparison of the laboratories F to I with reference laboratory A revealed excellent agreement rates from 92% to 100% (kappa values: 0.88 to 1.0) with an overall sensitivity of 97.5% (195/200) and specificity of 99.5% (199/200). CONCLUSIONS: The detection of HR-HPV as a group is highly reproducible with GP5+/6+ PCR-EIA provided that standardised protocols and validated reagents are used.     

Right heart function in impaired left ventricular diastolic function: 2D speckle tracking echocardiography–based and Doppler tissue imaging–based analysis of right atrial and ventricular function

Aim

The aim of our study was to describe right atrial (RA) and right ventricular (RV) function, assessed by Doppler tissue imaging and 2D speckle tracking echocardiography (2DSTE), in women with signs of early impaired left ventricular diastolic function (DD).

Methods and Results

In a cross‐sectional trial, standard parameters of diastolic and right heart function were investigated in 438 women of the Berlin Female Risk Evaluation (BEFRI) study. In a subset of women, average peak systolic RA strain (RAS), as well as the average peak systolic RV strain of the free wall (RVS free wall) and of all RV segments (average RV strain; RVS Avg), was analyzed using 2DSTE. Compared to women with normal diastolic function (DD0), RAS, RVS free wall and RVS Avg were significantly reduced in DD (43.1% ± 11.9%, ?26.7% ± 5.6%, and ?23.3% ± 3.5% in DD0; vs 35.1% ± 10.4%, ?23.9% ± 5.5%, and ?20.6% ± 3.8% in DD; P < .01). Peak RV myocardial velocity (RV‐IVV) and acceleration during isovolumetric contraction (RV‐IVA) were markedly higher in DD (15.0 ± 3.9 cm/s and 3.1 ± 1.0 m/s² in DD vs 11.9 ± 3.2 cm/s and 2.8 ± 0.8 m/s² in DD0; P < .05). RAS and RV‐IVV were significantly associated with DD after adjustment to age, BMI, and left atrial strain in multivariate regression analysis.

Conclusion

Systolic right heart function is significantly altered in DD. DTI as well as 2DSTE constitute sensitive echocardiographic tools that enable the diagnosis of impaired right heart mechanics in early‐staged DD.     

Population Pharmacokinetic/Pharmacodynamic Modeling of Guanfacine Effects on QTc and Heart Rate in Pediatric Patients

Using a previously developed population pharmacokinetic model, an exposure-response (ER) model was successfully developed to describe guanfacine plasma concentrations and changes in heart rate (HR) and the QT interval. Guanfacine exposure was associated with small decreases in HR and a small prolongation of the population-corrected QT (QTcP) interval. Based on the final ER model for effect of guanfacine on HR, the estimated population typical decrease in HR would be 2.3% (2.1–2.7%) of the baseline circadian HR for every 1 ng/mL of guanfacine exposure. A QTcP was developed for the analysis using the sampled population. An effect of sex on baseline-corrected QT (BQTP) was the only covariate effect in the final ER model for QTcP, its inclusion resulting in a typical baseline QTcP estimate that is 9 (5–13) ms higher for females. There was no evidence of QT-RR hysteresis. A linear model was used to relate guanfacine plasma concentrations to QTcP. The typical (95% confidence interval) slope parameter was estimated to be 0.941 (0.62–1.25) ms/ng/mL. The final model predicted an approximate 1-ms increase from baseline for every 1 ng/mL of guanfacine in plasma. The main predictor of QTcP prolongation was guanfacine exposure, which decreased with body weight and increased with dose.

Electronic supplementary material

The online version of this article (doi:10.1208/s12248-014-9645-0) contains supplementary material, which is available to authorized users.KEY WORDS: ADHD, guanfacine, pediatric, pharmacodynamics, pharmacokinetic