Cardiovascular dysplasia in Noonan's syndrome. Apropos of 64 cases

The multiple malformation syndrome with characteristic facies described by Jacqueline Noonan in 1963 is one of the most commonly encountered syndromes in paediatric cardiology. The series presented here comprises 64 cases, almost a quarter of which were familial (6 families). The morphotype (Turner phenotype with hypertelorism) can easily be recognized, but the variations, progressivity and resemblance to some similar syndromes imply a detailed analysis of a wide range of discriminant features. Short stature and webbed neck are less frequent than in Turner's syndrome, while mental debility and, mostly, cardiovascular lesions are much more frequent (the latter are present in 50-60% of the cases). The most typical cardiovascular lesion is pulmonary valve stenosis with dysplastic leaflets, or "atypical pulmonary stenosis syndrome", characterized by a curious electrical axis and above all, by left ventricular myocardiopathy with very peculiar deformations at ventriculography and 2D-echocardiography. In our series, myocardiopathy was even more frequent than dysplastic pulmonary valve stenosis (71.8% versus 64%). The dissemination of dysplastic lesions must be emphasized. They involve the aorta much more often than is usually reported (one-third of the cases); lesions of the lymphatic system are less frequent but may be severe. Occasionally, entirely different heart diseases, such as Fallot's tetralogy, are encountered. Owing to the relationship between its lesions and those of other multiple malformation syndromes, notably those of the phakomatosis group, and to the possibility of borderline cases with these syndromes, or even with other dystrophies, such as Williams-Beuren dystrophia, the cardiovascular dysplasia of Noonan's syndrome must be classified within the vast group of histodysplasias which are embryonic diseases of the "layers" or "neuro-ecto-mesodermoses" of unknown genetic mechanism.     

Breakdown of the brain’s functional network modularity with awareness

Neurobiological theories of awareness propose divergent accounts of the spatial extent of brain changes that support conscious perception. Whereas focal theories posit mostly local regional changes, global theories propose that awareness emerges from the propagation of neural signals across a broad extent of sensory and association cortex. Here we tested the scalar extent of brain changes associated with awareness using graph theoretical analysis applied to functional connectivity data acquired at ultra-high field while subjects performed a simple masked target detection task. We found that awareness of a visual target is associated with a degradation of the modularity of the brain’s functional networks brought about by an increase in intermodular functional connectivity. These results provide compelling evidence that awareness is associated with truly global changes in the brain’s functional connectivity.Three broad classes of models have been proposed to explain the neural basis of awareness, with these classes primarily differing on the predicted extent of neural information changes associated with conscious perception. According to focal theories, awareness results from local changes in neural activity in either the perceptual substrates (1–3) or in higher-level nodes of information processing pathways (4). By contrast, network-level theories posit that awareness is tightly associated with activation of parietofrontal attention networks of the brain (5–11). Finally, global models propose that awareness results from widespread changes in the activation state (12–15) and functional connectivity (16–19) of the brain. Though there is strong experimental support for network-level theories, there is scant experimental evidence in favor of truly sweeping, widespread changes in brain activity with conscious perception despite the fact that global scale models have recently come to prominence in the theoretical landscape of this field.Using a graph theoretical approach applied to ultra-high-field fMRI data, here we experimentally tested a key tenet of global theories: the widespread emergence of large-scale functional connectivity with awareness. Graph theory analyses are ideal tools to test global models of awareness because they can provide concise measures of the integration and segregation of interconnected nodes of a system (20). Applied to functional imaging data, we treat individual brain regions of interest (ROIs) as nodes, functional connectivity between ROIs as edges, and functional brain networks as interconnected modules of nodes. When examining a large set of ROIs that encompass the different networks of the human cerebral cortex (21, 22), we can apply graph theory analyses to estimate the extent to which key measures of global information processing are altered by the state of awareness. This approach has been previously applied to study differences in cognitive states (23–31). Although recent studies have taken advantage of graph theory analysis to examine the connectivity patterns that precede a conscious event (32) or following pharmacologically induced loss of consciousness (33), this approach had yet to be used for characterizing the topology associated with conscious target perception per se, a necessary test for global theories of awareness.If the changes with awareness are truly global, one should see such changes even if the task does not require complex discrimination, identification, and semantic processes that may recruit vast extents of cortical tissue that are not necessarily associated with conscious perception; in other words, these global changes should appear even for the simple conscious detection of a flashed disk. For this reason, we had participants perform an elementary masked target detection task (Fig. 1) while being scanned at ultra-high field (7 T). The task included three trial types: forward-masked, backward-masked, and no-target conditions. In the forward-masked (paracontrast) condition, a 133-ms-duration annular mask offset 33 ms before the target (a disk whose exterior border coincided with the interior border of the annulus) presented for 33 ms. In the backward-masked (metacontrast) condition, the order of mask/target presentation was reversed while keeping all timing parameters the same. Under such conditions, forward masking of targets has been shown to impair target detection more than backward masking (34, 35). Consequently, the mask/target orderings provided a manipulation of target awareness while maintaining the same mask and target presentation times across both forward- and backward-masked conditions. Because on each trial, participants made a detection response about the presence or absence of the target followed by a confidence rating on their response, subjects’ performance could be assessed on both an objective (discriminability index d′) and subjective (confidence rating) measure of awareness (36). In turn, only trials in which the target was either seen (aware) or unseen (unaware) at high confidence levels were used for analysis of brain imaging data. Finally, because the report of the percept was 12 s removed from the stimulus presentations (Fig. 1), the task design precluded initiation of the motor response itself from influencing estimates of awareness. Although response selection and motor preparation processes likely occur during this period, similar preparation would occur across all conditions.Open in a separate windowFig. 1.Schematic of behavioral paradigm with forward-masked and backward-masked trial types (no-target trials not shown). On each trial, participants responded whether they detected the target stimulus and indicated a confidence rating for their answer (Methods).     

The neural correlates of visual working memory encoding: a time-resolved fMRI study

The encoding of information into visual working memory (VWM) is not only a prerequisite step for efficient working memory, it is also considered to limit our ability to attend to, and be consciously aware of, task-relevant events. Despite its important role in visual cognition, the neural mechanisms underlying visual working memory encoding have not yet been specifically dissociated from those involved in perception and/or VWM maintenance. To isolate the brain substrates supporting VWM encoding, here we sought to identify, with time-resolved fMRI, brain regions whose temporal profile of activation tracked the time course of VWM encoding. We applied this approach to two different stimulus categories - colors and faces - that dramatically differ in their encoding time. While several cortical and subcortical regions were activated during the VWM encoding period, one of these regions in the lateral prefrontal cortex - the inferior frontal junction - showed a temporal activation profile associated with the duration of encoding and that could not be accounted for by either perceptual or general attentional effects. Moreover, this region corresponds to the prefrontal area previously implicated in ‘attentional blink’ paradigms demonstrating attentional limits to conscious perception. These results not only suggest that the inferior frontal junction is involved in VWM encoding, they also provide neural support for theories positing that VWM encoding is a rate-limiting process underlying our attentional limits to visual awareness.     

Biologic and structural evaluation of 80 surgically excised human umbilical vein grafts

Human umbilical vein is a valuable alternative to autogenous saphenous vein in lower-limb revascularization. However, the long-term patency is not as good. To understand better the reasons for this, the authors studied the biologic and structural changes occurring in 80 segments of human umbilical vein (HUV) grafts excised from 70 patients. Morphologic, histologic and scanning electron microscopy examinations were performed on each specimen. It was noted that increasing duration of implantation was associated with greater encapsulation and less surrounding inflammatory reaction. Twenty-six percent of clinically noninfected grafts were found to harbour bacteria. Bacteremic colonization was often in the folds of the luminal surface. As a result of these findings, the authors emphasize the need for complete excision of clinically infected grafts. Anastomoses between HUV segments are discouraged because they are associated with a high frequency of infection and a corresponding decrease in duration of implantation. Delamination of the wall was common, and such sites may represent areas at risk for further degradation. Continued surveillance of the biologic and structural changes occurring in excised grafts remains an important method in increasing our understanding of the evolutive complications of HUV grafts.     

Characterization of plasma proteins adsorbed onto biomaterials. By MALDI-TOFMS

The analysis of plasma proteins adsorbed onto a polyurethane (PU) biomaterial was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). This article marks the first study on MALDI-TOFMS analysis of multiple proteins adsorbed from plasma, in vitro, onto the surface of a biomaterial to easily enable their characterization. Plasma standards from three different hosts were placed in contact with non-porous PU, a model biomaterial. Following the use of washing protocols developed in our laboratory, the biomaterial was analyzed, directly, with MALDI-TOFMS. Proteins with molecular weights (Mr) ranging from ca. 6.5 to 150 kDa were observed in the mass spectra and characterized upon comparison with proteins of known Mr. The proteins observed were tentatively identified as those known to adsorb onto PU, both in vitro and in vivo. In an attempt to model in vivo sorption, the PU biomaterial was exposed to freshly collected canine plasma, in vitro, for different lengths of time. Corresponding MALDI-TOFMS spectra displayed increasing protein signal for a number of different proteins with increasing times of exposure to plasma. This method provided qualitative and semi-quantitative analysis of the proteins adsorbed onto the biomaterial surface.     

La chirurgie vasculaire avec effraction tissulaire minimale pour exclusion d''anévrisme : intérêts et limites des essais chez l''animalMinimally-invasive endovascular surgery for the treatement of aortic aneurysms : interest and limits in animal experimentation

The Vanguad™ endoprotheses were implanted transluminally through the femoral route and deployed at the site of surgically created aneurysms in the thoracic or abdominal aortas of dogs for prescheduled periods of implantation of 1 week, 1, 2 and 3 months. The in vivo dimensional stability of the endoprothesis was confirmed by angiography after insertion and before the sacrifice and by macroscopic observations after retrieval. Histological and scanning electron microscopic (SEM) studies were performed to assess the healing sequence of the device. Microscopic studies of the textile components and surface chemical analysis of the Nitinol wires by electron spectroscopy for chemical analysis (ESCA) were undertaken, after specimen cleaning to remove adherent tissue, to detect structural modifications to the textile structure and to evaluate the bioresilience of the Nitinol. Analysis of the angiograms after implantation and before the sacrifice revealed that morphological changes such as sliding and compression of the metal structure occurred initially after deployment and during implantation. Thrombogenicity of the luminal surface of the endoprotheses was low but the healing was still incomplete after 90 days of implantation. The lack of stability of the metal structure may explain the migration distally and the poor healing of the device. ESCA analysis showed that a physiosorbed passivation layer covered the surface of the Nitinol wires masking the nickel (Ni) component of the alloy. Ion bombardments of the surface of the wires confirmed the presence of a contaminated layer composed of carbon and other elements followed by a highly oxidized titanium (Ti) layer, and then, by the Ti/Ni alloy. Although innovative, the minimally-invasive endovascular technique for the treatment of aortic aneurysms is still in its infancy. Significant improvements are required in terms of ease of handling, effectiveness, innocuousness, biostability and healing.     

Complications of tension-free vaginal tape surgery: a multi-institutional review

OBJECTIVE: To analyse the complications of tension-free vaginal tape (TVT) surgery, a minimally invasive alternative for treating patients with stress urinary incontinence (SUI), at six institutions, and to review the management of these complications and their effect on patient outcome. PATIENTS AND METHODS: In all, 241 patients who had a TVT procedure by six urologists at six hospitals (two university and four community) were reviewed retrospectively by the same urologist. Complications during and after surgery, and their management, were analysed. RESULTS: Complications during surgery included bladder perforation in 48 patients (5.8%) and blood loss > 500 mL in 16 (2.5%). Immediate complications after surgery were urinary retention (>24 h after) in 47 patients (19.7%), pelvic haematoma in four (1.9%) and suprapubic wound infection in one (0.4%). Of the 47 patients in retention, 32 were in retention for <48 h and treated with an indwelling catheter. The 15 remaining patients were treated with an indwelling catheter (one) or clean intermittent catheterization for a mean of 22 days. To correct the retention the TVT was released in seven patients and the tape sectioned in three. Late complications were de novo urgency, persistent suprapubic discomfort and intravaginal tape erosion in 36 (15%), 18 (7.5%) and one (0.4%) patient, respectively. Most of these complications resolved with observation and medical management, but intravaginal tape erosion required partial resection of the tape with closure and repair of the vaginal mucosa. CONCLUSIONS: The present TVT complication rates were slightly higher than reported previously. This multi-institutional review in both academic and community hospitals may better reflect the morbidity of TVT insertion in clinical practice. TVT is a highly effective, minimally invasive method for treating SUI. A stricter definition of each complication and a better understanding of the mechanism of these complications may further improve the surgical outcome and decrease patient morbidity.     

Sublethal effects in avocet and stilt hatchlings from selenium-contaminated sites

Excess selenium (Se) in the aquatic food chain is embryotoxic and teratogenic to avocets, stilts, and other waterbirds. American avocet (Recurvirostra americana) and black-necked stilt (Himantopus mexicanus) eggs were collected from three sites in the Tulare Lake Basin of California, USA, and hatched in the laboratory. These sites included the Tulare Lake Drainage District-north (TLDD-N, water 2.5 ppb Se), TLDD-south (TLDD-S, water 8.6 ppb Se), and Westfarmers (WF, water 190 ppb Se). Highest egg Se concentrations occurred at WF (geometric mean 31.4 ppm dry wt for avocets and 20.5 ppm dry wt for stilts). Mean egg Se concentrations were 6.7 ppm for avocets and 8.4 ppm for stilts at TLDD-S, and 3.3 ppm for avocets and 2.3 ppm for stilts at TLDD-N. Hatching success and incidence of malformations did not differ among sites, but yolk sac-free hatching weights and bone lengths were less for avocets at the WF site, whereas liver weights and liver to body weight ratios were greater at that site. With increasing Se concentration, oxidative stress was most apparent in avocet hatchlings from WF: hepatic glutathione (GSH) peroxidase activity increased, glucose-6-phosphate dehydrogenase activity decreased, and oxidized glutathione (GSSG) concentration as well as the ratio of GSSG to reduced GSH concentration increased. In stilts, hepatic GSH concentration was lower in WF hatchlings. In conclusion, our findings of Se-impaired embryo growth and hepatotoxicity in avocet hatchlings suggest that oxidative stress observed in hatchlings may be related to these biological effects and may serve as a potential bioindicator of subsequent impaired functions.     

New polyester arterial prostheses from great britain: anin vitro andin vivo evaluation

Two models of knitted velour polyester prostheses have been developed in Great Britain, i.e. the VP1200K and the VP50K Triaxial. The evaluation of these new devices in vitro and in vivo in dogs has demonstrated that, while the first model has similar surgical, mechanical and healing characteristics in the short term to other commercial knitted velour prostheses, the second model has lower water permeability and superior strength and dimensional stability. On the basis of these results, clinical investigations can be undertaken.