Mechanical limitation during CO2 rebreathing in young patients with cystic fibrosis

The aim of the study was to determine whether a decrease in the ventilatory response to carbon dioxide (CO2) in children with cystic fibrosis (CF) is related to a mechanical limitation of the respiratory muscle capacity. The ventilatory response during CO2 rebreathing was performed in 15 patients (mean forced expiratory volume in 1 s (FEV1): 37 +/- 21% predicted, mean arterial CO2: 41+/- 5 mmHg). The slope of the minute ventilation normalised for weight per mmHg CO2 increment correlated negatively with respiratory muscle output, assessed by the oesophageal (p = 0.002), the diaphragmatic pressure time product (p = 0.01), and the tension time index (p = 0.005). In addition, this slope was correlated with dynamic lung compliance (p < 0.0001) and FEV1 (p = 0.03) but not with airway resistance and maximal transdiaphragmatic pressure. Therefore, an excessive load imposed on the respiratory muscles explains the blunting of the ventilatory response to CO2 in young patients with CF.     

Electromagnetic brain activity evoked by affective stimuli in schizophrenia

Schizophrenia is typically associated with cognitive deficits, but symptoms also point to alterations in the processing of affective material, with potential impact on behavioral performance. This impact may unfold on multiple time scales, but initial processing of rapidly unfolding social cues may be particularly important. MEG-assessed regional brain activity associated with the capacity to process the emotional content of rapid visual stimuli (3/s) was examined in 12 individuals with schizophrenia and 12 matched controls. Patients showed less differentiation of emotional versus neutral stimuli 90-300 ms following picture onset. Together with group differences in the lateral topography of valence effects, these results are discussed as evidence of deficient automatic processing of emotionally potent stimuli in schizophrenia.     

Dosimetric characterization of a novel intracavitary mold applicator for 192Ir high dose rate endorectal brachytherapy treatment

The dosimetric properties of a novel intracavitary mold applicator for 192Ir high dose rate (HDR) endorectal cancer treatment have been investigated using Monte Carlo (MC) simulations and experimental methods. The 28 cm long applicator has a flexible structure made of silicone rubber for easy passage into cavities with deep-seated tumors. It consists of eight source catheters arranged around a central cavity for shielding insertion, and is compatible for use with an endocavitary balloon. A phase space model of the HDR source has been validated for dose calculations using the GEANT4 MC code. GAFCHROMIC EBT model film was used to measure dose distributions in water around shielded and unshielded applicators with two loading configurations, and to quantify the shielding effect of a balloon injected with an iodine solution (300 mg I/mL). The film calibration procedure was performed in water using an 192Ir HDR source. Ionization chamber measurements in a Lucite phantom show that placing a tungsten rod in the applicator attenuates the dose in the shielded region by up to 85%. Inserting the shielded applicator into a water-filled balloon pushes the neighboring tissues away from the radiation source, and the resulting geometric displacement reduces the dose by up to 53%; another 8% dose reduction can be achieved when the balloon is injected with an iodine solution. All experimental results agree with the GEANT4 calculations within measurement uncertainties.     

In vivo behavior of calcium phosphate scaffolds with four different pore sizes

The goal of the present study was to assess the effect of macropore size on the in vivo behavior of ceramic scaffolds. For that purpose, beta-tricalcium phosphate (beta-TCP) cylinders with four different macropore sizes (150, 260, 510, and 1220 microm) were implanted into drill hole defects in cancellous bone of sheep and their resorption behavior was followed for 6, 12 and 24 weeks. The scaffolds were evaluated for biocompatibility, and new bone formation was observed macroscopically, histologically and histomorphometrically. Histomorphometrical measurements were performed for the whole defect area and for the area subdivided into three concentric rings (outer, medial, and inner ring). All implants were tolerated very well as evidenced by the low amount of inflammatory cells and the absence of macroscopic signs of inflammation. Resorption proceeded fast since less than 5% ceramic remained at 24-week implantation. Hardly any effect of macropore size was observed on the in vivo response. Samples with an intermediate macropore size (510 microm) were resorbed significantly faster than samples with smaller macropore sizes (150 and 260 microm). However, this fast resorption was associated with a lower bone content and a higher soft tissue content. At 12 and 24 weeks, the latter differences had disappeared. Bone was more abundant in the outer ring than in the rest of the blocks at 6 weeks, and in the outer and medial ring compared to the inner ring at 12 weeks.     

Starting and stopping mechanisms of absence epileptic seizures are revealed by hazard functions

We show that the hazard function provides useful information about the starting and the stopping mechanisms of absence epileptic seizures. The hazard function quantifies changes in the probability that an event (respectively, the starting and the stopping of a seizure) occurs in some small time interval given that it has not occurred yet. It informs us about changes in the concentration of endogenous substances that modulate the neuronal signalling properties of (parts of) the brain. In a pharmacological experiment, we used the hazard function to study the effect of a GABA-transaminase inhibitor (vigabatrin) on the starting and the stopping mechanisms of absence epileptic seizures in a genetic rat model of absence epilepsy (the WAG/Rij rat). This experiment showed that a high GABA level changed the stopping mechanism of the absence epileptic seizures, creating much better conditions for very long seizures to develop. With respect to the starting mechanism, it was found that both with a high and a low GABA level, there was evidence for a recovery mechanism that decreases the probability that a new seizure starts. Initially, this probability is larger with a high GABA level, but gradually it converges to the same constant baseline probability as in the condition with a low GABA level.     

Immunocytochemical analysis of rat vagus nerve by antibodies against glycogen phosphorylase isozymes

Glycogen is an endogenous store of glucose equivalents for energy metabolism in many tissues. The brain contains a significant amount of glycogen the role of which as an energy reserve is currently under debate. Apparently little is known concerning a possible role of glycogen in peripheral nerves. We have demonstrated immunocytochemically the presence of glycogen phosphorylase (GP), a key enzyme in glycogen metabolism, in large and small axons of the rat vagus nerve, but not in Schwann cells. Furthermore, the isozyme-specific antibodies applied detected only the presence of the brain isoform BB of GP, but not the muscle isoform MM. This is in agreement with the occurrence of solely the BB isoform in the few brain and spinal cord neurons that contain GP. In contrast, astroglial cells in brain and spinal cord have previously been shown to contain both isoforms. Since GP isozymes are regulated differentially, the expression of isoform BB may provide hints to possible functions of glycogen in the vagus nerve.     

Prognostic implications of atypical histologic features in choroid plexus papilloma

The prognostic significance of atypical histologic features in choroid plexus tumors remains uncertain. Therefore, a series of 164 choroid plexus tumors was evaluated for the presence of atypical histologic features, including mitotic activity, increased cellularity, nuclear pleomorphism, blurring of papillary growth pattern, and necrosis. The impact of histopathologic and clinical features on the probability of recurrence and survival was investigated. Twenty-four tumors displaying frank signs of malignancy were diagnosed as choroid plexus carcinoma according to World Health Organization criteria. Of 124 choroid plexus papillomas that had not received adjuvant treatment, 46 tumors (37%) displayed at least one atypical feature, including increased cellularity (n = 25 [20%]), mitotic activity (> or =2 mitoses per 10 high-power fields; n = 19 [15%]), nuclear pleomorphism (n = 16 [13%]), solid growth (n = 15 [12%]), and necrosis (n = 5 [4%]). Only one tumor-related death, but 10 recurrences, were observed on a mean observation time of 58 months. On univariate analysis, incomplete surgical resection (p = 0.03) and mitotic activity (p < 0.001) were the only clinicopathologic factors associated with recurrence. Using a multivariate model, an independent effect of mitotic activity on the probability of recurrence could be confirmed (p = 0.001). Because mitotic activity is the sole atypical histologic feature independently associated with recurrence, we propose to define atypical choroid plexus papilloma by mitotic activity (> or =2 mitoses per 10 high-power fields) corresponding to World Health Organization grade II, thus adjoining other intermediate tumor entities associated with increased mitotic activity such as atypical meningioma. Close follow up of patients harboring atypical choroid plexus papillomas may be warranted.     

Atypical language impairment in two siblings: relationship with electrical status epilepticus during slow wave sleep

We report the case of a young girl who presented severe learning disabilities in oral and written language related to a continuous spike-waves during slow sleep (CSWS) syndrome. A sleep EEG recording obtained in her younger brother, who presented a clinical pattern suggesting developmental dysphasia, also showed a CSWS syndrome. These two clinical cases underscore the need to look for this syndrome in the siblings of an affected child when learning difficulties appear in a child who previously had normal psychomotor development.     

A pathomechanical concept explains muscle loss and fatty muscular changes following surgical tendon release.

Following tendon tear, the musculo-tendinous unit retracts permanently, looses muscle fibre volume and is infiltrated with fat. This is currently considered to be an unexplained degenerative process. In a sheep model of chronic tendon tear with delayed tendon repair (35 weeks after tendon release), we studied the nature of these muscle changes in eight experimental animals. At sacrifice (75 weeks after tendon release) the muscle had retracted by 1.7+/-0.5 cm (9% of entire length, p<0.0001), the pennation angle had increased from 22+/-2.5 degrees to 50+/-11 degrees (p<0.0001) and the mean muscle fibre length had shortened from 32+/-3 to 16+/-5 mm (50%, p<0.0001). In electron and light microscopy, we found essentially normal muscle fibres with an unaltered fibre diameter and myofibrillar structure, while interstitial fat and fibrous tissue had increased from 3.9% to 45.9% (p<0.0001) of the muscle volume. Geometric modelling showed that the increase of the pennation angle separates the muscle fibre bundles mechanically like limbs of a parallelogram. Infiltrating fat cells fill the created space between the reoriented muscle fibres which may be quantitatively calculated without affecting the structural properties of the muscle cells. Fatty infiltration is therefore not seen as a degenerative process but a necessary rearrangement of the tissue after macroarchitectural changes caused by musculo-tendinous retraction.