Comparative Finite Element Model Analysis of Ascending Aortic Flow in Bicuspid and Tricuspid Aortic Valve

In bicuspid aortic valve (BAV) disease, the role of genetic and hemodynamic factors influencing ascending aortic pathology is controversial. To test the effect of BAV geometry on ascending aortic flow, a finite element analysis was undertaken. A surface model of aortic root and ascending aorta was obtained from magnetic resonance images of patients with BAV and tricuspid aortic valve using segmentation facilities of the image processing code Vascular Modeling Toolkit (developed at the Mario Negri Institute). Analytical models of bicuspid (antero‐posterior [AP], type 1 and latero‐lateral, type 2 commissures) and tricuspid orifices were mathematically defined and turned into a volumetric mesh of linear tetrahedra for computational fluid dynamics simulations. Numerical simulations were performed with the finite element code LifeV. Flow velocity fields were assessed for four levels: aortic annulus, sinus of Valsalva, sinotubular junction, and ascending aorta. Comparison of finite element analysis of bicuspid and tricuspid aortic valve showed different blood flow velocity pattern. Flow in bicuspid configurations showed asymmetrical distribution of velocity field toward the convexity of mid‐ascending aorta returning symmetrical in distal ascending aorta. On the contrary, tricuspid flow was symmetrical in each aortic segment. Comparing type 1 BAV with type 2 BAV, more pronounced recirculation zones were noticed in the latter. Finally, we found that in both BAV configurations, maximum wall shear stress is highly localized at the convex portion of the mid‐ascending aorta level. Comparison between models showed asymmetrical and higher flow velocity in bicuspid models, in particular in the AP configuration. Asymmetry was more pronounced at the aortic level known to be more exposed to aneurysm formation in bicuspid patients. This supports the hypothesis that hemodynamic factors may contribute to ascending aortic pathology in this subset of patients.     

Iodine-131 metaiodobenzylguanidine scintigraphy for localization of lesions in children with neuroblastoma: comparison with computed tomography and ultrasonography

Iodine-131 metaiodobenzylguanidine (MIBG) scintigraphy, computed tomography (CT) and ultrasonography (US) were used to localize tumour lesions in 28 children with histologically proven neuroblastoma. Overall, a total of 73 lesions were detected on imaging studies. MIBG scintigraphy, CT and US localized 63 (86%), 49 (67%) and 36 (49%) of these lesions, respectively. The findings of the three imaging techniques were concordant in respect of only 31 (42%) of the lesions. The best agreement among MIBG scintigraphy, CT and US was observed for abdominal lesions (the techniques were concordant for 22 of 23 lesions, i.e. 96%). MIBG scintigraphy detected nine out of ten (90%) liver metastases, but agreement with CT and US was observed in only six instances (60%). The imaging findings were concordant in respect of only two (33%) out of six lymph node metastases; the MIBG scan was normal in the other four cases. Imaging agreement was observed for a lesion located in the pelvis. MIBG and CT findings were concordant in four lesions located in the chest, but US was not performed. MIBG scintigraphy depicted the majority (96%) of the skeletal lesions (23/24); CT showed five of these, but, again, US was not performed. The imaging findings were not concordant as regards the remaining five lesions located in different anatomical sites. The results indicated that MIBG imaging is more sensitive that CT and US in localizing the majority of neuroblastoma lesions. Since the metastatic spread of neuroblastoma is unpredictable, we recommend MIBG scintigraphy as the initial imaging modality for staging of these patients. US and, particularly, CT should be performed thereafter to clarify the anatomical detail of the lesions detected on MIBG scans, or when MIBG findings are normal or equivocal.     

Hemifacial spasm, vertebrobasilar dolichoectasia and neurofibromatosis type 1

Hemifacial spasm (HFS) is usually produced by compression of the facial nerve by tortuous blood vessels at the root exit zone, including vertebrobasilar dolichoectasia (VBD). Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with a variety of symptoms, affecting mainly the skin and nervous system. Cerebrovascular abnormalities are becoming a recognized complication of the disease and the most constantly described lesions are stenosis and occlusions affecting the internal carotid artery. VBD has rarely been associated with NF1. We report a 38-year-old female patient with HFS produced by VBD with NF1 presenting with other cerebrovascular abnormalities associated with this disease. We discuss the possible association between these three entities, assuming that a causal relationship may be established and that VBD is part of the spectrum of vascular abnormalities caused by NF1 in this patient.     

Tremor severity in Parkinson's disease and cortical changes of areas controlling movement sequencing: A preliminary study

There remains much to learn about the changes in cortical anatomy that are associated with tremor severity in Parkinson's disease (PD). For this reason, we used a combination of structural neuroimaging to measure cortical thickness and neurophysiological studies to analyze whether PD tremor was associated with cortex integrity. Magnetic resonance imaging and neurophysiological assessment were performed in 13 nondemented PD patients (9 women, 69.2%) with a clearly tremor‐dominant phenotype. Cortical reconstruction and volumetric segmentation were performed with the Freesurfer image analysis software. Assessment of tremor was performed by means of high‐density surface electromyography (hdEMG) and inertial measurement units (IMUs). Individual motor unit discharge patterns were identified from surface hdEMG and tremor metrics quantifying motor unit synchronization from IMUs. Increased motor unit synchronization (i.e., more severe tremor) was associated with cortical changes (i.e., atrophy) in wide‐spread cortical areas, including caudal middle frontal regions bilaterally (dorsal premotor cortices), left inferior parietal lobe (posterior parietal cortex), left lateral orbitofrontal cortex, cingulate cortex bilaterally, left posterior and transverse temporal cortex, and left occipital lobe, as well as reduced left middle temporal volume. Given that the majority of these areas are involved in controlling movement sequencing, our results support Albert's classic hypothesis that PD tremor may be the result of an involuntary activation of a program of motor behavior used in the genesis of rapid voluntary alternating movements.     

15The effect of Lower Esophageal Sphincter (LES) electrical stimulation on LES pressure

Background: Electrical stimulation (ES) of the stomach has been shown to modulate LESP. Electrical stimulation, using neural high frequency stimulation (NGES) can induce contractions of the smooth muscle of the gut. The purpose of this study was to determine if electrical stimulation of the LES can affect LESP. Methods: Four female hound dogs, weight: 20–25 kg, underwent an esophagostomy that allowed the introduction of a sleeve manometry catheter into the esophagus. They were also implanted with a pair of electrodes along the longitudinal axis of the LES. After 3 weeks of recovery, they underwent esophageal manometry recording during control and ES, performed randomly on separate days, using 4 different stimulations: 1‐Low frequency: freq: 6 cycles/min, pulse: 350 milisec, amp: 5 mAmp; 2 High‐frequency: freq: 50 Hz, pulse: 1 milisec, amp: 5 mAmp; 3‐ NGES: freq: 50 Hz, pulse:20 milisec, amp:10 volts; 4‐ High‐frequency, circular: freq: 20 Hz, pulse:1 milisec, amp:5 mAmp. All recordings were performed 1 hour after consumption of 3 ounces of canned dog food, to prevent fluctuations in LESP and under mild sedation (acepromazine 0.5 mg kg^­1). Tests consisted, during ES days, of 3 periods of 20 minutes each: control , stimulation and post stimulation. The effect of NGES was also tested under anesthesia and following administration of L‐NAME 50 mg kg^­1 IV. and also atropine 0.05 mg kg^­1 IV. Analysis: area under the curve (AUC) and pressure were compared among the 3 periods. Data shown as mean ± SD, ANOVA and t‐test, p < 0.05. Results: Sustained increase in LESP was observed during low frequency stimulation, 32.1 ± 12.8 vs. 42.4 ± 18.0 vs. 50.1 ± 23.6, control vs. stimulation vs. post stimulation respectively, p = 0.013. AUC also significantly increased during and after stimulation, 39,320.3 ± 15,722 vs. 51,294 ± 21,826 vs. 59,823.6 ± 28,198.4 mmHgxsec, control vs. stimulation vs. post stimulation respectively, p = 0.01. There was no significant change with other types of ES. NGES induced an initial rise in LESP followed within few seconds by relaxation with slow resumption of pressure over a 1 minute period. L‐NAME increased LESP and augmented the initial rise in LESP following NGES but markedly diminished or abolished the relaxation phase. Atropine lowered LESP and abolished the initial rise in LESP induced by NGES. Conclusions: Low frequency ES of the LES increases LESP in conscious dogs. NGES has dual effect on LESP: an initial stimulation, cholinergically mediated, followed by relaxation mediated by nitric oxide.     

Cutaneous lymphomas showing prominent granulomatous component: clinicopathological features in a series of 16 cases

Background  The presence of a prominent granulomatous tissue reaction in skin biopsies from primary cutaneous or systemic malignant lymphomas with secondary cutaneous involvement is a rare but well-known phenomenon.
Objective  This paper aims to characterize and study a series of cutaneous lymphomas showing a prominent granulomatous component.
Patients and methods  The clinical, histopathological and evolutive features of granulomatous variants of mycosis fungoides (5 patients, 2 of them associating 'granulomatous slack skin' features), Sézary syndrome (1 patient), CD30⁺ cutaneous T-cell lymphoma (2 patients), CD4⁺ small/medium pleomorphic cutaneous T-cell lymphoma (1 patient), primary cutaneous B-cell lymphoma (3 patients) and peripheral T-cell lymphoma with secondary epithelioid granulomatous cutaneous involvement (4 patients) were reviewed.
Results  The observed features were clinically non-distinctive. Only those cases presenting with granulomatous slack skin features were clinically suspected (2 patients). Non-necrotizing granulomata (11 patients) and granuloma annulare-like (4 patients) were the most frequently observed histopathological patterns. In five cases, no diagnostic lymphomatous involvement was initially observed. From our series, no definite conclusions regarding prognosis could be established.
Conclusion  The diagnosis of cutaneous lymphoma may be difficult when a prominent cutaneous granulomatous inflammatory infiltrate obscures the true neoplastic nature of the condition. However, the presence of concomitant lymphoid atypia may help to suspect the diagnosis. In doubtful cases, the clinical evolution and the demonstration of a monoclonal lymphoid B- or T-cell population may lead to a definite diagnosis.

Conflicts of interest

None declared.     

Association of G-protein-coupled receptor 154 with asthma and total IgE in a population of the Caribbean coast of Colombia

Background G protein‐coupled receptor 154 was described as an asthma susceptibility gene by positional cloning. It has been subsequently associated with asthma and other inflammatory diseases in several populations with different ethnic origin. Replication of associations adds reliability to these findings. Objective To analyze the association of G protein‐coupled receptor 154 with asthma and total and mite‐specific IgE levels in a population of the Caribbean Coast of Colombia. Methods We genotyped seven single nucleotide proteins (SNPs) in GPR154 in 475 asthmatics, 394 controls and 116 families from Cartagena, Colombia using either SnaPshot or TaqMan. Total and specific IgE against Blomia tropicalis and Dermatophagoides pteronyssinus were determined by ELISA. Hardy–Weinberg equilibrium was assessed and case–control and family‐based analyses were performed to evaluate the association between the SNPs and their haplotypes and asthma and IgE. Association analyses in the case–control dataset were corrected by population stratification using 52 ancestry informative markers. Results Allelic distribution was similar to that described in other populations. Two SNPs were associated with the same direction of the effect in both datasets. Allele A of Hopo546333 was protective for asthma (case–control OR: 0.42; 95% CI: 0.17–0.99, P=0.042; P=0.043; families Z score=?2,236; P=0.025). Similarly, allele C of rs740347 conferred low risk for asthma (OR: 0.44; 95% CI: 0.28–0.70, P=0.00017; P_c=0.00037) and total IgE (OR: 0.29; 95% CI: 0.09–0.88, P=0.015; P_c=0.030) in the case–control study and families (Z score=?3.207, P=0.0013; Z score=?3.182, P=0.0014, respectively). Haplotype CCAGGT was associated with total IgE (OR: 1.76; 95% CI: 1.14–2.71, P=0.006, P_c=0.007) in the case–controls group and CGCGGT with both phenotypes (P=0.044 and P=0.032, respectively) in families. Neither SNPs nor haplotypes were associated with levels of mite‐specific IgE. Conclusions Our findings in a sample of asthmatics from Colombia suggest a relevant role of G protein‐coupled receptor 154 in the pathogenesis of asthma and allergy.     

Estimating the Burden of Disease for Autism Spectrum Disorders in Spain in 2003

Autism Spectrum Disorders (ASD) are lifelong neurodevelopmental disabilities. Burden of Disease is an indicator that provides important information on health status and outcomes such as premature mortality and disability. In order to estimate the burden of disease of ASD in the Spanish population during 2003, we followed the procedures used in the WHO Global Burden of Disease Study. ASD generated 43,928 Disability Adjusted Life Years (DALY) in Spain in 2003, from which 33,797 were attributable to Autistic Disorder and 10,131 were caused by Asperger’s Disorder and Pervasive Developmental Disorder-Not Otherwise Specified. DALY could be a useful tool for health policy makers for setting health service priorities, allocating available resources effectively and providing a comparable measure of output for early intervention.     

Correction to: Effect of a Focused Social and Communication Intervention on Preterm Children with ASD: A Pilot Study

Journal of Autism and Developmental Disorders - A correction to this paper has been published: https://doi.org/10.1007/s10803-021-05109-2