Deposition of Foradil P in human lungs: comparison of in vitro and in vivo data.

In order to characterize the efficacy of dry powder inhalers, in vitro measurements are much easier to perform than human deposition studies, especially in early stages of drug development. In this study, lung deposition and delivered dose of radiolabeled Foradil P inhaled with the Aerolizer were measured in 10 healthy subjects. These data were then compared with data derived from an in vitro assessment of the device output and particle size distribution combined with mathematical modeling of lung deposition (modified ICRP-model). Delivered dose and lung deposition increased slightly but statistically significant with the inhalation peak flow in both the in vivo data and the in vitro data. The delivered dose ranged from 60% to 80% and lung deposition, relative to the fill weight, from 13% to 28%. Differences between the in vitro and in vivo data were slight and statistically not significant. This study indicates that in vitro assessment of device performance, in combination with lung deposition delivery data, are in good agreement with deposition data measured in healthy subjects. Since there was only a slight flow rate dependency of lung deposition without clinical relevance, it may additionally be concluded that the Aerolizer is a robust, easy to handle inhalation device with stable and reproducible drug delivery characteristics.     

Prevalence of Galen's anastomosis: an anatomical and comparative study

An anatomical study of 50 fresh adult human cadavers was performed in order to verify prevalence of Galen's anastomosis (GA) and to evaluate whether factors such as gender, ethnicity, side of the neck, and individual stature may interfere with GA prevalence. The results were analysed using the Chi-square test, Student t-test, and F-Snedecor test. GA was observed in 87 of 100 dissections. There was no statistically significant difference regarding GA prevalence between groups separated by ethnicity (p = 0.853), gender (p = 0.198), side of the neck (p = 0.766), or individual height (p = 0.199). Therefore, the GA was a frequent anatomical finding, and this result was not influenced by any studied factor. Comparing our data with previous studies, we also concluded that the GA seems to play an important role in the innervation of the larynx, even though its function remains unclear. Also, it is reasonable to consider GA a constant anatomical constituent.     

Magnetic resonance imaging of the pancreas at 3.0 tesla: qualitative and quantitative comparison with 1.5 tesla

OBJECTIVES: We sought to perform a preliminary comparison of signal-to-noise ratio (SNR) and image quality for magnetic resonance imaging (MRI) of the pancreas at 1.5 and 3 T. MATERIALS AND METHODS: Two imaging cohorts were studied using a T2-weighted, single-shot fast spin-echo pulse sequence and a T1-weighted, fat-suppressed 3D gradient-echo pulse sequence. In the first cohort, 4 subjects were imaged using identical imaging parameters before and after contrast administration at 1.5 and 3.0 T. The SNR was quantified for the pancreas as well as for the liver, spleen, and muscle. In a second cohort of 12 subjects in whom the receiver bandwidth was adjusted for field strength, SNR measurements and qualitative rankings of image quality were performed. RESULTS: In the study cohort using identical imaging parameters at both magnetic field strengths, the mean (SD) ratios of SNR at 3.0 to 1.5 T of the single-shot fast spin-echo images for the pancreas, liver, spleen, and muscle were 1.63 (0.39), 1.82 (0.39), 1.45 (0.18), 2.01 (0.16), respectively. For the precontrast fat-suppressed 3D gradient-echo sequence, the corresponding ratios were 1.28 (0.29), 1.26 (0.30), 1.16 (0.27), and 1.76 (0.45), respectively; for the arterial phase, the corresponding ratios were 2.02 (0.28), 1.60 (0.42), 1.47 (0.26), and 1.94 (0.32), respectively; and for the delayed postcontrast phase, the corresponding ratios were 1.63 (0.51), 2.01 (0.25), 1.66 (0.06), and 2.31 (0.47), respectively. The SNR benefit of 3.0 T was significantly greater on contrast-enhanced as compared with noncontrast T1-weighted 3D gradient-echo images. In the second study cohort, SNR was superior at 3.0 T, although the use of a reduced readout bandwidth at 1.5 T substantially diminished the advantage of the higher field system. With qualitative comparison of images obtained at the 2 magnetic field strengths, the fat-suppressed 3D gradient-echo images obtained at 3.0 T were preferred, whereas the single shot fast spin-echo images obtained at 1.5 T were preferred because of better signal homogeneity. CONCLUSIONS: Our results in a small cohort of volunteers and patients demonstrate a marked improvement in SNR at 3.0 T compared with 1.5 T (by a factor of 2 in some cases) when identical imaging parameters were used. The SNR advantage at 3.0 T is diminished but persists when the receiver bandwidth is adjusted for magnetic field strength. The results suggest that 3.0 T may offer promise for improved body MRI, although further technical development to optimize SNR and improve signal homogeneity will be needed before its full potential can be achieved.     

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.     

Predictors for successful PBSC collection on the fourth day of G‐CSF‐induced mobilization in allogeneic stem cell donors

Peripheral blood stem cells (PBSCs) used for allogeneic transplantation are collected by apheresis after pre‐treatment of donors with G‐CSF. Using modern apheresis devices stem cells can be collected more efficiently. It was studied whether collection on the 4th instead of the 5th day after initiation of G‐CSF treatment might be feasible. Stem cell yields that could have been collected on day 4 were calculated in two cohorts treated with 10 µg/kg G‐CSF once daily (n = 106, cohort I) or 5 µg/kg twice daily schedule (n = 85, cohort II). Harvests were predicted using the median collection efficiency (CE) of the apheresis machine and regarded successful when > 5.0 x10⁶ CD34^+/kg recipient body weight. Successful harvests at day 4 could have been obtained in only 22.6% and 41.2% of donors in cohort I and II respectively, while the expected successful collections on day 5 were 55.7% and 76.5%. Individual donor factors that correlated with a successful harvest on day 4 were weight, BMI, age, ratio donor/recipient weight and total G‐CSF dose in cohort I, whereas ratio donor/recipient weight was the only significant predictor in cohort II. Donor weight, BMI and total G‐CSF dose correlated positively with CD34⁺ values in the blood on day 4 in all donors. However, donor characteristics were not able to be used as strong predictors in daily practice. In conclusion, PBSC collection on day 4 will not result in a successful harvest in most stem cell donors, however using a twice daily G‐CSF scheme increases the yield.