Role of lung fluid volume in growth and maturation of the fetal sheep lung.

We studied the effects of alterations in lung fluid volume on growth and maturation of the fetal lung. In a chronic fetal sheep preparation, right fetal lung volume was decreased by drainage of lung fluid while the volume of the left lung was expanded by mainstem bronchus ligation leading to lung fluid retention. After an experimental period of 25 d (from 105 to 129 d of gestation, term = 145 d), the right (deflated) lung was significantly hypoplastic and contained less DNA than the controls; 175.15 +/- 55.18 vs. 346.77 +/- 61.97 mg, respectively; P less than 0.001. In contrast, the left (expanded) lung was significantly hyperplastic and contained more DNA than the controls; 390.74 +/- 103.53 vs. 238.85 +/- 33.32 mg, respectively; P = 0.001. Biochemical indices of lung maturation, including total phospholipids, phosphatidylcholine, and disaturated phosphatidylcholine content expressed per unit of tissue DNA, were no different when comparing the hypoplastic, hyperplastic, and control lungs. These findings demonstrate that fetal lung cell multiplication is influenced by local distension with lung fluid, while the biochemical maturation of fetal lung surfactant is under systemic control.     

Emerging topics in Reelin function

Reelin signalling in the early developing cortex regulates radial migration of cortical neurons. Later in development, Reelin promotes maturation of dendrites and dendritic spines. Finally, in the mature brain, it is involved in modulating synaptic function. In recent years, efforts to identify downstream signalling events induced by binding of Reelin to lipoprotein receptors led to the characterization of novel components of the Reelin signalling cascade. In the present review, we first address distinct functions of the Reelin receptors Apoer2 and Vldlr in cortical layer formation, followed by a discussion on the recently identified downstream effector molecule n‐cofilin, involved in regulating actin cytoskeletal dynamics required for coordinated neuronal migration. Next, we discuss possible functions of the recently identified Reelin–Notch signalling crosstalk, and new aspects of the role of Reelin in the formation of the dentate radial glial scaffold. Finally, progress in characterizing the function of Reelin in modulating synaptic function in the adult brain is summarized. The present review has been inspired by a session entitled ‘Functions of Reelin in the developing and adult hippocampus’, held at the Spring Hippocampal Research Conference in Verona/Italy, June 2009.     

Validation of the EORTC QLQ-C30 and EORTC QLQ-H&N35 in patients with laryngeal cancer after surgery

Background.

The aim of this study was to test the validity of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core Module (QLQ‐C30) and Head and Neck Module (QLQ‐H&N35) for patients who have undergone surgery due to laryngeal cancer.

Methods.

A total of 323 patients from 6 different centers in Germany who had been operated on completed the QLQ‐C30 and the QLQ‐H&N35 in addition to being surveyed in a personal interview.

Results.

Multitrait scaling analysis confirmed the proposed scale structure of both questionnaires. Cronbach's alpha of the QLQ‐C30 scales ranged from 0.64 (Cognitive Functioning) to 0.94 (Global Health Status); the alpha of the QLQ‐H&N35 ranged from 0.55 (Speech) to 0.90 (Sexuality). Known‐groups comparisons showed multiple differences in sociodemographic and clinical variables.

Conclusion.

It can be concluded that the QLQ‐H&N35, in conjunction with the QLQ‐C30, is a reliable instrument that is able to differentiate between diverse groups of patients with laryngeal cancer after surgery. © 2008 Wiley Periodicals, Inc. Head Neck, 2009     

Midazolam-pain, but one cannot remember it: a survey among Southern German endoscopists

BACKGROUND: Benzodiazepines, especially midazolam, are the most frequently used agents for gastrointestinal endoscopy worldwide. Among other parameters the quality of sedation is determined by patients' satisfaction assessed after endoscopy. This approach is misleading as the potent amnestic effect of midazolam conceals pain actually suffered during the endoscopic procedure involving distraction of the endoscopists from their actual tasks by audible reactions and defense movements. In this study, we eliminated the influence of patients' amnesia on the assessment of the quality of sedation and rather interviewed endoscopists and their assistant personnel about their experience with midazolam sedation. We replaced the mostly vague term 'compliance' by terms which unequivocally describe the reactions of the patient during an unpleasant endoscopy. METHODS: A short survey consisting of 12 questions was developed. The questionnaires were distributed to the participants - 115 endoscopists and their assistants - of a tutorial about sedation for gastrointestinal endoscopy in three major Southern German cities. The questionnaire retrieved the endoscopists' experience regarding patients' discomfort or pain under sedation with midazolam, their wish for better sedative agents, their preferred sedative regimens, their medical specialty and their professional experience. RESULTS: Participants were highly experienced with the majority having more than 10,000 procedures and a median of 18 years of endoscopic experience; 77% of endoscopists utilized midazolam for sedation. Ninety-eight percent of the questioned physicians felt that patients have pain during endoscopy with midazolam+/-opioid, but do not remember later. Ninety-two percent reported that it happens that patients moan aloud because of pain and almost half of the endoscopists (48%) reported of screaming. The majority of the endoscopists (91%) reported fierce defense movements with midazolam or the need to hold the patient down on the examination couch because of fierce movements, respectively (75%). Seventy percent of the endoscopists wished to have the rooms for endoscopy preferably soundproof away from the waiting room and 93% wished for better sedative agents. CONCLUSIONS: Midazolam was rated as insufficient for sedation by both endoscopists and their assistant personnel. A wish for better sedative drugs exists.     

MR myocardial perfusion imaging with k-space and time broad-use linear acquisition speed-up technique: feasibility study

The purpose of this study was to prospectively evaluate the diagnostic accuracy of a cardiovascular magnetic resonance (MR) k-space and time (k-t) broad-use linear acquisition speed-up technique (BLAST) accelerated perfusion sequence for depicting clinically relevant coronary artery disease (CAD), with use of coronary angiography as the reference standard. The local ethics committee approved this study, and informed consent was obtained from 40 patients (28 men, 12 women; mean age, 61 years +/- 8 [standard deviation]) scheduled for coronary catheterization. A balanced steady-state free precession pulse sequence (2.6 x 2.6 x 10 mm) with a net k-t acceleration factor of 3.8 (repetition time msec/echo time msec, 3.2/1.6; flip angle, 50 degrees ) was applied. Visual analysis of perfusion images and quantitative analysis of signal-time curves obtained in the myocardium were performed by using segmental myocardial upslope, peak enhancement, and their respective ratios. Visual analysis revealed sensitivity, specificity, and diagnostic accuracy of 86%, 78%, and 83%, respectively, in the detection of coronary stenoses with at least 50% luminal narrowing. Significant (P < .05) changes between ischemic and remote segments could be shown for all perfusion indexes applied. Use of myocardial perfusion imaging with k-t BLAST for accelerated data acquisition is feasible in the identification of patients with substantial CAD (coronary stenosis >or= 50%). Supplemental material: http://radiology.rsnajnls.org/cgi/content/full/245/3/863/DC1.     

Improved bulk myocardial motion suppression for navigator-gated coronary magnetic resonance imaging

PURPOSE: To evaluate the impact of a new, cross-correlation based method for compensation of respiratory induced motion of the heart using an individually adapted three-dimensional (3D) translation or affine transformation approach. MATERIALS AND METHODS: A total of 32 patients underwent a routine cardiac MR examination. In each patient, a calibration scan was performed during free-breathing to register breathing-related motion within a 3D ellipsoid registration kernel covering the entire heart. Three navigators were employed for all three spatial dimensions (feet-head, anterior-posterior, and left-right) and the optimal translatory correction factors for each spatial dimension were determined. In addition, the cross-correlations for different motion models (no compensation, fixed 1D-translation, adapted 3D-translation, and affine transformation) were calculated. RESULTS: The mean correction factor for the feet-head direction was 0.45 +/- 0.13. Though the mean correction factors for the anterior-posterior and left-right direction were nearly zero (-0.01 +/- 0.08 and 0.02 +/- 0.09, respectively), the correction factors exceeded the amount of 0.1 in 12 (19%) and in 19 patients (30%), respectively. All motion compensation models showed significantly higher cross-correlations when compared to "no compensation" (P < 0.05). In particular, the affine transformation algorithm achieved the highest cross-correlation values (88.3 +/- 5.1%) with a significant increase compared to fixed 1D translation (84.7 +/- 6.5%, P < 0.05). CONCLUSION: A considerable number of patients demonstrated relevant breathing-related movement of the heart in the anterior-posterior or left-right direction in addition to the predominant breathing-related movement in the feet-head direction. Thus, it is recommended to compensate for all three spatial dimensions. The affine transformation algorithm combined with three navigators significantly improved breathing-related cardiac motion compensation when compared to the conventionally applied 1D translation with a fixed correction factor.     

Exogenous reelin prevents granule cell dispersion in experimental epilepsy

Temporal lobe epilepsy (TLE) is often accompanied by granule cell dispersion (GCD), a migration defect of granule cells in the dentate gyrus. We have previously shown that a decrease in the expression of reelin, an extracellular matrix protein important for neuronal positioning, is associated with the development of GCD in TLE patients. Here, we used unilateral intrahippocampal injection of kainate (KA) in adult mice which is also associated with GCD formation and a decrease of reelin expression. In this mouse epilepsy model we aimed to prevent GCD development by the application of exogenous reelin. As a prerequisite we analyzed whether the reelin signaling transduction cascade was preserved in the KA-injected hippocampus. Using in situ hybridization and Western blot analysis we found that the expression of the reelin signaling components, apolipoprotein E receptor 2, the very-low-density lipoprotein receptor and the intracellular adaptor protein disabled 1, was maintained in dentate granule cells after KA injection. Next, recombinant reelin was infused into the KA-injected hippocampus by osmotic minipumps over a period of 2 weeks. Quantitative analysis of granule cell layer width revealed a significant reduction of GCD in reelin-treated, but not in saline-infused animals when compared to KA injection alone. Our findings highlight the crucial role of reelin for the maintenance of granule cell lamination in the dentate gyrus of adult mice and show that a reelin deficiency is causally involved in GCD development.     

Dopaminergic modulation of auditory cortex-dependent memory consolidation through mTOR

Previous studies in the auditory cortex of Mongolian gerbils on discrimination learning of the direction of frequency-modulated tones (FMs) revealed that long-term memory formation involves activation of the dopaminergic system, activity of the protein kinase mammalian target of rapamycin (mTOR), and protein synthesis. This led to the hypothesis that the dopaminergic system might modulate memory formation via regulation of mTOR, which is implicated in translational control. Here, we report that the D1/D5 dopamine receptor agonist SKF-38393 substantially improved gerbils' FM discrimination learning when administered systemically or locally into the auditory cortex shortly before, shortly after, or 1 day before conditioning. Although acquisition performance during initial training was normal, the discrimination of FMs was enhanced during retraining performed hours or days after agonist injection compared with vehicle-injected controls. The D1/D5 receptor antagonist SCH-23390, the mTOR inhibitor rapamycin, and the protein synthesis blocker anisomycin suppressed this effect. By immunohistochemistry, D1 dopamine receptors were identified in the gerbil auditory cortex predominantly in the infragranular layers. Together, these findings suggest that in the gerbil auditory cortex dopaminergic inputs regulate mTOR-mediated, protein synthesis-dependent mechanisms, thus controlling for hours or days the consolidation of memory required for the discrimination of complex auditory stimuli.