Correlation between neuroimaging, neurological phenotype, and functional outcomes in Wilson's disease.

INTRODUCTION: Wilson's disease (WD) is associated with a variety of movement disorders and progressive neurological dysfunction. The aim of this study was to correlate baseline brain magnetic resonance imaging (MRI) features with clinical phenotype and long-term outcomes in chronically treated WD patients. METHODS: Patients were retrospectively selected from an institutional database. Two experienced neuroradiologists reviewed baseline brain MRI. Functional assessment was performed using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) scale, and disease severity was classified using the Global Assessment Scale for Wilson's Disease (GASWD). RESULTS: Of 27 patients selected, 14 were female (51.9%), with a mean (standard deviation [SD]) age at onset of 19.5 (7.1) years. Neurological symptoms developed in 22 patients (81.5%), with hyperkinetic symptoms being the most common (70.4%). Baseline brain MRI showed abnormal findings in 18 cases (66.7%), including T2 hyperintensities in 59.3% and atrophy in 29.6%. After a mean (SD) follow-up of 20.9 (11.0) years, WD patients had a mean score of 19.2 (10.2) on WHODAS 2.0 and 6.4 (5.7) on GASWD. The presence of hyperkinetic symptoms correlated with putaminal T2 hyperintensities (p = 0.003), putaminal T2 hypointensities (p = 0.009), and mesencephalic T2 hyperintensities (p = 0.009). Increased functional disability was associated with brain atrophy (p = 0.007), diffusion abnormalities (p = 0.013), and burden of T2 hyperintensities (p = 0.002). A stepwise regression model identified atrophy as a predictor of increased WHODAS 2.0 (p = 0.023) and GASWD (p = 0.007) scores. CONCLUSIONS: Atrophy and, to a lesser extent, deep T2 hyperintensity are associated with functional disability and disease severity in long-term follow-up of WD patients.

Acute variceal bleeding and out-of-hours endoscopy: Evaluation of an emergency care setting according to Baveno VI guidelines adherence.

BACKGROUND: The extent to which patients with acute variceal bleeding (AVB) receive recommended care is largely unknown. AIM: to evaluate the adherence of the 4 major Baveno VI recommendations [vasoactive agents, prophylactic antibiotic, esophagogastroduodenoscopy (EGD) within 12 hours, endoscopic variceal ligation (EVL)] as a marker of quality of an emergency model. METHODS: Retrospective evaluation of AVB admissions to a tertiary centre in which endoscopy was available 24hours-a-day, with a regional out-of-hours service at night (the furthest hospital is 200Km away). Patients were divided in directly admitted or transferred from other centres. RESULTS: 210 AVB patients were included; 101 (48.1%) were directly admitted. The majority of patients were submitted to vasoactive agents (85.7%) and prophylactic antibiotics (79%) before EGD. In 178 patients (84.8%) endoscopy was performed within 12h and EVL was the procedure of choice in 116 (74.8%) (only oesophageal varices). No significant differences were observed between directly admitted and transferred patients in adherence rates. Overall rebleeding rate was 8.6%, in-hospital mortality 11.4% and 6-week mortality 20%. CONCLUSION: Adherence to quality metrics was high which might have played a vital role for reported outcomes. These results suggest that this model of care, provides accessibility and equity in access to urgent endoscopy.

[The importance of diffusing capacity as a complementary study to plethysmography in smokers]. / A importância do estudo da difusão alvéolo-capilar, como complemento da pletismografia, na avaliação funcional de fumadores.

UNLABELLED: This study comprised 194 male and female heavy smokers or ex-smokers (>or= 1 pack-year) aged between 20 and 82, whose symptoms varied. Cases were only selected from patients with normal whole-body plethysmography. Subjects with any significant pathology and occupational risk factors were excluded from the study. Varying degrees of symptoms were found and a range of results from normal plethysmography examination, with abnormal levels of alveolar-capillary transfer, determined by the single-breath method to analyse CO (TLCO and TLCO-VA) coefficients. Using the chi-square test for statistical analysis of the sample revealed a significant variation in sensitivity between both parameters (p=0.0001). Possible limitations of using the single-breath method, of were reduced in this study (ventilatory restriction with Vital Capacity <1.5 litres) by the routine plethysmography results seen. Likewise, the presence of alterations in ventilatory distribution was, in principle, minimised by the absence of TLCsb/TLCplet values below 0.85% CONCLUSIONS: Normal plethysmography results in heavy or ex-smokers are not enough to confirm normal respiratory function, as a large percentage of cases present abnormalities in the alveolar-capillary transfer factor for CO. Alveolar limitation was considered not only anatomically, but also from a functional perspective.

Noise and the respiratory system.

Noise-induced pulmonary pathology is still an issue that is regarded with much suspicion despite the significant body of evidence demonstrating that acoustic phenomena target the respiratory tract. The goal of this review paper is threefold: a) to describe acoustic phenomena as an agent of disease, and the inadequacies of current legislation regarding noise-induced, non-auditory pathology; b) to trace how the interest in noise-induced pulmonary pathology emerged within the scope of studies on vibroacoustic disease; and c) to bring to light other studies denouncing noise as an agent of disease that impinges on the respiratory tract. As concluding remarks, future perspectives in LFN-related research will be discussed. The need for animal models will be emphasized.

Respiratory epithelia in Wistar rats.

Morphofunctional changes of respiratory epithelia became the object of intense study in Wistar rats after previous research showed that occupationally-simulated exposure to low frequency noise (500 Hz, including infrasound) induced irreversible lesions in these tissues. Aspects of normal respiratory epithelia in rats are lacking in the literature, and are the object of this report. Ten Wistar rats were kept in silence, fed standard rat food, and had unrestrained access to water (treated in accordance with 86/609/CE). The animals were sacrificed at 3.5 months of age, and respiratory epithelial fragments were excised and prepared for scanning (SEM) and transmission (TEM) electron microscopy. Brush cells (BC) were frequently observed with TEM, but with SEM they were often covered by the cilia of neighbouring cells. BC were always observed at the center of a ring of secretory cells (SC), in a rosetta-shaped formation. In TEM, the microvilli of SC surrounding the BC were uniform, and had the same density and shape in all cells. Multivesicular bodies were identified in areas within the BC. Formation and budding of vesicles from ciliary plasma membranes and from BC microvilli were frequently observed in both TEM and SEM. These data contribute to the understanding of the BC function.

[Respiratory epithelia in Wistar rats after 48 hours of continuous exposure to low frequency noise]. / O epitélio respiratório em ratos Wistar após 48 horas de exposição contínua ao ruído de baixa frequência.

Previous studies show that exposure to low frequency noise (LFN) (< or =500 Hz, including infrasound) produces irreversible lesions in Wistar rat respiratory epithelia. Recovery periods for LFN-induced lesions have thus become an object of interest. Changes in the respiratory epithelia of Wistar rats after continuous short-term exposure to LFN are described. Twelve rats were exposed to continuous LFN for 48 hrs, and 10 age-matched rats were kept in silence. Animals were treated in accordance with 86/609/CE. After exposure ceased, two rodents were sacrificed immediately, and another two after 6, 12, 24, 48 hrs, and 7 days of post-exposure silence. Respiratory epithelial fragments were prepared for light and scanning/transmission electron microscopy. Six hours after exposure, intense and irregular cellular tumefaction was visible and rosetta structures, formed by secretory cells (SC) centered on a brush cell (BC), were identifiable. Cilia were shorter and shaggy. BC microvilli tended to group, losing the uniform distribution seen in controls. Twelve hours after exposure, cell ballooning was still present, BC shape was highly irregular and microvilli were grouped. SC microvilli were still shorter than controls. Seven days after exposure, controls and exposed were indistinguishable. LFN-induced epithelial lesions seem to be reversible if recovery periods are respected.

[Respiratory epithelia in Wistar rats born in low frequency noise plus varying amounts of additional exposure]. / O epitélio respiratório em ratos Wistar nascidos em ruído de baixa frequência e expostos a ruído adicional.

Earlier studies of Wistar rat respiratory epithelia exposed to low frequency noise (LFN) (< or =500 Hz, including infrasound) showed that LFN effects trauma on the respiratory tract. In rats gestated and born in LFN environments, trauma was still treated in accordance with 86/609/EC. Respiratory epithelial fragments were prepared for light and scanning/transmission electron microscopy. Group A brush cell (BC) microvilli tended to group together; in Group B they were clearly clustered together, and in Groups C-F they became fused. Rosetta structures (rings of secretory cells centered on a BC) were visible in Groups A-D and difficult to identify in Groups E,F. The amount of sheared cilia increased with exposure time, as did the images of cellular de-differentiation. LFN exposure induces severe trauma on the respiratory epithelial cells in these rats.