Laryngeal involvement in pemphigus vulgaris: a proposed classification

Objective: (1) To investigate the incidence of laryngeal involvement in a large series of patients with pemphigus vulgaris, using endoscopic examination, (2) to describe the lesions, and (3) to establish a classification of laryngeal involvement in pemphigus vulgaris based on the location of the lesions. Study design: Prospective study. Methods: A total of 40 sequentially treated pemphigus vulgaris patients, diagnosed using clinical, histological and immunofluorescence criteria, were evaluated for laryngeal manifestations using endoscopic examination. The results were used to establish a graded classification of laryngeal involvement according to the location of the lesions. Results: Active laryngeal lesions (ulcers or blisters) were found in 16 patients (40 per cent). Of these, 37.5 per cent were classified as grade I, 20 per cent as grade II, 20 per cent as grade III and 17.5 per cent as grade IV. Conclusion: Laryngeal involvement is common in pemphigus vulgaris and must be considered at the point of diagnosis. Grade I lesions are the most frequent

Laryngeal involvement in pemphigus vulgaris: a proposed classification

Objective: (1) To investigate the incidence of laryngeal involvement in a large series of patients with pemphigus vulgaris, using endoscopic examination, (2) to describe the lesions, and (3) to establish a classification of laryngeal involvement in pemphigus vulgaris based on the location of the lesions. Study design: Prospective study. Methods: A total of 40 sequentially treated pemphigus vulgaris patients, diagnosed using clinical, histological and immunofluorescence criteria, were evaluated for laryngeal manifestations using endoscopic examination. The results were used to establish a graded classification of laryngeal involvement according to the location of the lesions. Results: Active laryngeal lesions (ulcers or blisters) were found in 16 patients (40 per cent). Of these, 37.5 per cent were classified as grade I, 20 per cent as grade II, 20 per cent as grade III and 17.5 per cent as grade IV. Conclusion: Laryngeal involvement is common in pemphigus vulgaris and must be considered at the point of diagnosis. Grade I lesions are the most frequent

Depression with melancholic features is associated with higher long-term risk for dementia

BACKGROUND: Depression has been reported to increase the risk of subsequently developing dementia, but the nature of this relation remains to be elucidated. Depression can be a prodrome/manifestation of dementia or an early risk factor, and the effect may differ according to depression subtypes. Our aim was to study the association between early-onset depression and different depression subtypes, and the later occurrence of dementia. METHODS: We conducted a cohort study including 322 subjects with depression, recruited between 1977 and 1984. A comparison cohort (non-exposed) was recruited retrospectively, to include 322 subjects admitted at the same hospital for routine surgery (appendicectomy or cholecystectomy), at the same period as the depressed cohort. Subjects were contacted again between 2009 and 2014, to assess their dementia status. We computed the risk for dementia in subjects with early onset depression and quantified the association between different depression subtypes (namely melancholic, anxious, and psychotic) and dementia. RESULTS: The odds of dementia were increased by 2.90 times (95% C.I. 1.61-5.21; p<0.0001) for the depressed cohort when compared to the surgical cohort. When the analysis was restricted to patients younger than 45 years old at baseline, the odds for dementia in the depressed cohort were also significantly higher when compared to the surgical cohort (8.53; 95% C.I. 2.40-30.16). In the multivariate Cox analysis, subjects having depression with melancholic features had an increased risk for developing dementia compared to those without melancholic features (HR=3.64; 95% C.I. 1.78-11.26; p=0.025). LIMITATIONS: About 59% of the participants with depression and 53% of those non-exposed were lost during follow up. The inclusion of biological biomarkers would strengthen the results. The sample included a low number of bipolar patients. CONCLUSIONS: These results support depression as an early risk factor for dementia. Depression with melancholic features was found as an important risk factor for dementia, playing a main role in the relation between these disorders

Delayed auditory feedback simulates features of nonfluent primary progressive aphasia.

The pathophysiology of nonfluent primary progressive aphasia (nfvPPA) remains poorly understood. Here, we compared quantitatively speech parameters in patients with nfvPPA versus healthy older individuals under altered auditory feedback, which has been shown to modulate normal speech output. Patients (n=15) and healthy volunteers (n=17) were recorded while reading aloud under delayed auditory feedback [DAF] with latency 0, 50 or 200 ms and under DAF at 200 ms plus 0.5 octave upward pitch shift. DAF in healthy older individuals was associated with reduced speech rate and emergence of speech sound errors, particularly at latency 200 ms. Up to a third of the healthy older group under DAF showed speech slowing and frequency of speech sound errors within the range of the nfvPPA cohort. Our findings suggest that (in addition to any anterior, primary language output disorder) these key features of nfvPPA may reflect distorted speech input signal processing, as simulated by DAF. DAF may constitute a novel candidate pathophysiological model of posterior dorsal cortical language pathway dysfunction in nfvPPA

Probing the evolution of molecular cloud structure II: From chaos to confinement

We present an analysis of the large-scale molecular cloud structure and of the stability of clumpy structures in nearby molecular clouds. In our recent work, we identified a structural transition in molecular clouds by studying the probability distributions of gas column densities in them. In this paper, we further examine the nature of this transition. The transition takes place at the visual extinction of A_V^tail = 2-4 mag, or equivalently, at \Sigma^tail = 40-80 Ms pc^{-2}. The clumps identified above this limit have wide ranges of masses and sizes, but a remarkably constant mean volume density of n = 10^3 cm^{-3}. This is 5-10 times larger than the density of the medium surrounding the clumps. By examining the stability of the clumps, we show that they are gravitationally unbound entities, and that the external pressure from the parental molecular cloud is a significant source of confining pressure for them. Then, the structural transition at A_V^tail may be linked to a transition between this population and the surrounding medium. The star formation rates in the clouds correlate strongly with the total mass in the clumps, i.e, with the mass above A_V^tail, dropping abruptly below that threshold. These results imply that the formation of pressure confined clumps introduces a prerequisite for star formation. Furthermore, they give a physically motivated explanation for the recently reported relation between the star formation rates and the amount of dense material in molecular clouds. Likewise, they give rise to a natural threshold for star formation at A_V^tail.Comment: 11 pages, 12 figures, accepted for publication in Astronomy and Astrophysic

Decrease in APP and CP mRNA expression in Alzheimer’s disease patients suggests impairment of cellular iron export in this dementia

Recentemente tem-se assistido a um acumular de evidência sugerindo a implicação de uma desregulação do metabolismo do ferro (Fe) na fisiopatologia da doença de Alzheimer (DA). Neste trabalho, pretendemos esclarecer melhor os mecanismos moleculares subjacentes à homeostasia deste metal na DA, particularmente ao nível do efluxo celular. Assim, mediu-se em células mononucleares do sangue periférico de 73 doentes com DA e 74 controlos a expressão de genes diretamente envolvidos na regulação e exportação celular de Fe, utilizando a técnica de PCR quantitativo. Os resultados mostraram uma diminuição significativa na expressão dos genes aconitase (ACO1; P=0,007); ceruloplasmina (CP; P<0,001) e proteína precursora de beta amilóide (APP; P=0,006) em doentes com DA comparativamente com os voluntários saudáveis. Estas observações apontam para uma diminuição significativa da expressão dos genes associados com a exportação de Fe celular mediada pela ferroportina na DA. Assim, o presente estudo reforça resultados anteriores que mostram alterações no metabolismo do Fe e podem estar na origem da retenção intracelular deste metal e aumento de stress oxidativo caraterísticos desta patologia.A dysregulation of iron (Fe) metabolism in Alzheimer’s disease (AD) has been suggested previously. Herein, we intended to further clarify the molecular mechanisms underlying Fe homeostasis in AD particularly at the level of cellular iron efflux. Thus, the expression of specific Fe metabolism-related genes directly involved in Fe regulation and export was assessed by quantitative PCR in peripheral blood mononuclear cells (PBMCs) from 73 AD patients and 74 controls. A significant decrease in the expression of aconitase 1 (ACO1; P=0.007); ceruloplasmin (CP; P<0.001) and amyloid peptide precursor (APP; P=0.006) genes was fund in AD patients compared with healthy volunteers. These observations point out to a significant downregulation of the expression of genes associated with ferroportin-mediated cellular Fe export in PBMCs from AD patients. The present findings support previous studies suggesting impairment of Fe homeostasis in AD, which may lead to cellular Fe retention and oxidative stress, a typical feature of this disease