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1.
Clin Exp Dermatol ; 47(4): 717-723, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34826142

RESUMO

BACKGROUND: The rare inversa subtype of recessive dystrophic epidermolysis bullosa (RDEB-I) is characterized by predominant intertriginous skin blistering and marked mucosal involvement. Specific recessive missense mutations in the collagen VII triple helix are implicated in the disease. To date, otological complications have been reported infrequently in this patient group. METHODS: We conducted an observational, retrospective, double institution case record review of patients with RDEB-I who presented with otological complications between January 2000 and June 2020. Diagnosis was established on the basis of clinical features, family history and mutation analysis of the COL7A1 gene. RESULTS: In total, 11 (44%) of 25 patients with RDEB-I in our database (2 paediatric, 9 adult; mean age 40.9 years, range 8-72 years) experienced otological complications. Of these 11 patients, 10 (90.9%) had recurrent otitis externa, 7 (63.6%) had meatal stenosis and 7 (63.6%) had recurrent blistering of the external auditory canals. All 11 patients reported hearing difficulties, with conductive hearing loss confirmed by audiology testing in 6 (54.5%) of these. Of the 11 patients, 3 (27.3%) went on to have implantable hearing aids [2 bone-anchored hearing aids (BAHA) and 1 middle ear implant (MEI)] fitted with favourable outcome, while a fourth paediatric patient presented with a cholesteatoma that was surgically managed. DISCUSSION: We observed a higher prevalence of otological morbidity in RDEB-I than previously reported, and present the first case of cholesteatoma in epidermolysis bullosa (EB). Our data indicate that BAHA and MEI are safe and effective treatment options for hearing loss in EB. Clinicians should be vigilant in screening for ear symptoms in RDEB-I and consider early referral to an Ear, Nose and Throat specialist.


Assuntos
Epidermólise Bolhosa Distrófica , Epidermólise Bolhosa , Adolescente , Adulto , Idoso , Criança , Colágeno Tipo VII/genética , Epidermólise Bolhosa/genética , Epidermólise Bolhosa Distrófica/complicações , Epidermólise Bolhosa Distrófica/genética , Genes Recessivos , Humanos , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Estudos Retrospectivos , Adulto Jovem
2.
J Eur Acad Dermatol Venereol ; 36(7): 973-986, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35238435

RESUMO

The broad differential diagnosis of neonatal erythroderma often poses a diagnostic challenge. Mortality of neonatal erythroderma is high due to complications of the erythroderma itself and the occasionally severe and life-threatening underlying disease. Early correct recognition of the underlying cause leads to better treatment and prognosis. Currently, neonatal erythroderma is approached on a case-by-case basis. The purpose of this scoping review was to develop a diagnostic approach in neonatal erythroderma. After a systematic literature search in Embase (January 1990 - May 2020, 74 cases of neonatal erythroderma were identified, and 50+ diagnoses could be extracted. Main causes were the ichthyoses (40%) and primary immunodeficiencies (35%). Congenital erythroderma was present in 64% (47/74) of the cases, predominantly with congenital ichthyosis (11/11; 100%), Netherton syndrome (12/14, 86%) and Omenn syndrome (11/23, 48%). Time until diagnosis ranged from 102 days to 116 days for cases of non-congenital erythroderma and congenital erythroderma respectively. Among the 74 identified cases a total of 17 patients (23%) died within a mean of 158 days and were related to Omenn syndrome (35%), graft-versus-host disease (67%) and Netherton syndrome (18%). Disease history and physical examination are summarized in this paper. Age of onset and a collodion membrane can help to narrow the differential diagnoses. Investigations of blood, histology, hair analysis, genetic analysis and clinical imaging are summarized and discussed. A standard blood investigation is proposed, and the need for skin biopsies with lympho-epithelial Kazal-type related Inhibitor staining is highlighted. Overall, this review shows that diagnostic procedures narrow the differential diagnosis in neonatal erythroderma. A 6-step flowchart for the diagnostic approach for neonatal erythroderma during the first month of life is proposed. The approach was made with the support of expert leaders from international multidisciplinary collaborations in the European Reference Network Skin-subthematic group Ichthyosis.


Assuntos
Dermatite Esfoliativa , Ictiose Lamelar , Ictiose , Síndrome de Netherton , Imunodeficiência Combinada Severa , Dermatite Esfoliativa/etiologia , Diagnóstico Diferencial , Humanos , Ictiose/genética , Recém-Nascido , Síndrome de Netherton/complicações , Imunodeficiência Combinada Severa/complicações
3.
Br J Dermatol ; 183(4): 614-627, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32017015

RESUMO

BACKGROUND: Several new genes and clinical subtypes have been identified since the publication in 2014 of the report of the last International Consensus Meeting on Epidermolysis Bullosa (EB). OBJECTIVES: We sought to reclassify disorders with skin fragility, with a focus on EB, based on new clinical and molecular data. METHODS: This was a consensus expert review. RESULTS: In this latest consensus report, we introduce the concept of genetic disorders with skin fragility, of which classical EB represents the prototype. Other disorders with skin fragility, where blisters are a minor part of the clinical picture or are not seen because skin cleavage is very superficial, are classified as separate categories. These include peeling skin disorders, erosive disorders, hyperkeratotic disorders, and connective tissue disorders with skin fragility. Because of the common manifestation of skin fragility, these 'EB-related' disorders should be considered under the EB umbrella in terms of medical and socioeconomic provision of care. CONCLUSIONS: The proposed classification scheme should be of value both to clinicians and researchers, emphasizing both clinical and genetic features of EB. What is already known about this topic? Epidermolysis bullosa (EB) is a group of genetic disorders with skin blistering. The last updated recommendations on diagnosis and classification were published in 2014. What does this study add? We introduce the concept of genetic disorders with skin fragility, of which classical EB represents the prototype. Clinical and genetic aspects, genotype-phenotype correlations, disease-modifying factors and natural history of EB are reviewed. Other disorders with skin fragility, e.g. peeling skin disorders, erosive disorders, hyperkeratotic disorders, and connective tissue disorders with skin fragility are classified as separate categories; these 'EB-related' disorders should be considered under the EB umbrella in terms of medical and socioeconomic provision of care. Linked Comment: Pope. Br J Dermatol 2020; 183:603.


Assuntos
Epidermólise Bolhosa , Vesícula , Consenso , Epidermólise Bolhosa/diagnóstico , Epidermólise Bolhosa/genética , Estudos de Associação Genética , Humanos , Pele
4.
Br J Dermatol ; 182(3): 729-737, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31168818

RESUMO

BACKGROUND: Recessive forms of congenital ichthyosis encompass a group of rare inherited disorders of keratinization leading to dry, scaly skin. So far, 13 genes have been implicated, but there is a paucity of data on genotype-phenotype correlation in some populations. OBJECTIVES: We compiled an English cohort of 146 individuals with recessive ichthyosis and assessed genotype-phenotype correlation. METHODS: Deep phenotyping was undertaken by history-taking and clinical examination. DNA was screened for mutations using a next-generation sequencing ichthyosis gene panel and Sanger sequencing. RESULTS: Cases were recruited from 13 National Health Service sites in England, with 65% of patients aged < 16 years at enrolment. Pathogenic biallelic mutations were found in 83% of cases, with the candidate gene spread as follows: TGM1 29%, NIPAL4 12%, ABCA12 12%, ALOX12B 9%, ALOXE3 7%, SLC27A4 5%, CERS3 3%, CYP4F22 3%, PNPLA1 2%, SDR9C7 1%. Clinically, a new sign, an anteriorly overfolded ear at birth, was noted in 43% of patients with ALOX12B mutations. The need for intensive care stay (P = 0·004), and hand deformities (P < 0·001), were associated with ABCA12 mutations. Self-improving collodion ichthyosis occurred in 8% of the cases (mostly TGM1 and ALOX12B mutations) but could not be predicted precisely from neonatal phenotype or genotype. CONCLUSIONS: These data refine genotype-phenotype correlation for recessive forms of ichthyosis in England, demonstrating the spectrum of disease features and comorbidities, as well as the gene pathologies therein. Collectively, the data from these patients provide a valuable resource for further clinical assessment, improving clinical care and the possibility of future stratified management. What's already known about this topic? Recessive forms of ichthyosis are rare but often difficult to diagnose. Mutations in 13 genes are known to cause recessive forms of ichthyosis: ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, LIPN, NIPAL4, PNPLA1, SDR9C7, SLC27A4, SULT2B1, ST14 and TGM1. Some phenotypic features may associate with certain gene mutations, but paradigms for genotype-phenotype correlation need refining. What does this study add? The genotypic spectrum of recessive ichthyosis in England (based on 146 cases) comprises TGM1 (29%), NIPAL4 (12%), ABCA12 (12%), ALOX12B (9%), ALOXE3 (7%), SLC27A4 (5%), CERS3 (3%), CYP4F22 (3%), PNPLA1 (2%) and SDR9C7 (1%). New or particular phenotypic clues were defined for mutations in ALOX12B, ABCA12, CYP4F22, NIPAL4, SDR9C7 and TGM1, either in neonates or in later life, which allow for greater diagnostic precision. In around 17% of cases, the molecular basis of recessive ichthyosis remains unknown.


Assuntos
Ictiose Lamelar , Ictiose , Transportadores de Cassetes de Ligação de ATP/genética , Adolescente , Criança , Pré-Escolar , Inglaterra/epidemiologia , Proteínas de Transporte de Ácido Graxo , Genes Recessivos , Estudos de Associação Genética , Humanos , Ictiose/genética , Ictiose Lamelar/genética , Lactente , Recém-Nascido , Lipase , Mutação/genética , Oxirredutases
5.
Internist (Berl) ; 60(10): 1102-1105, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31451847

RESUMO

A 46-year-old immunosuppressed patient presented with a breast implant-associated infection 10 years after breast augmentation in Southeast Asia. No pathogen was identified in the initial conventional microbiological workup. Subsequently, infection with Mycobacterium abscessus-a nontuberculous mycobacteria-was diagnosed using a special culture technique. Increased rates of such infections are reported after cosmetic surgery in foreign countries, presumably due to inoculation with these ubiquitous pathogens. This case highlights the fact that the differential diagnosis and thus the microbiological workup should be extended in cases without initial pathogen detection.


Assuntos
Implantes de Mama/efeitos adversos , Corpos Estranhos/microbiologia , Mastodinia/etiologia , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Micobactérias não Tuberculosas/isolamento & purificação , Infecções Relacionadas à Prótese/microbiologia , Infecção da Ferida Cirúrgica/microbiologia , Implantes de Mama/microbiologia , Febre/etiologia , Humanos , Hospedeiro Imunocomprometido , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/microbiologia
6.
Br J Dermatol ; 179(3): 582-589, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29774538

RESUMO

BACKGROUND: Infantile haemangiomas (IH) are the most common vascular tumours of infancy. Despite their frequency and potential complications, there are currently no unified U.K. guidelines for the treatment of IH with propranolol. There are still uncertainties and diverse opinions regarding indications, pretreatment investigations, its use in PHACES (posterior fossa malformations-haemangiomas-arterial anomalies-cardiac defects-eye abnormalities-sternal cleft and supraumbilical raphe) syndrome and cessation of treatment. OBJECTIVES: To provide unified guidelines for the treatment of IH with propranolol. METHODS: This study used a modified Delphi technique, which involved an international treatment survey, a systematic evidence review of the literature, a face-to-face multidisciplinary panel meeting and anonymous voting. RESULTS: The expert panel achieved consensus on 47 statements in eight categories, including indications and contraindications for starting propranolol, pretreatment investigations, starting and target dose, monitoring of adverse effects, the use of propranolol in PHACES syndrome and how to stop treatment. CONCLUSIONS: These consensus guidelines will help to standardize and simplify the treatment of IH with oral propranolol across the U.K. and assist in clinical decision-making.


Assuntos
Coartação Aórtica/tratamento farmacológico , Dermatologia/normas , Anormalidades do Olho/tratamento farmacológico , Hemangioma/tratamento farmacológico , Síndromes Neurocutâneas/tratamento farmacológico , Pediatria/normas , Propranolol/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Administração Oral , Tomada de Decisão Clínica , Consenso , Técnica Delphi , Humanos , Lactente , Sociedades Médicas/normas , Resultado do Tratamento , Reino Unido
7.
J Water Health ; 16(5): 750-761, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30285956

RESUMO

Hydraulic or filtration efficiency of residential swimming pools, quantified in terms of residence time characteristics, is critical to disinfection and thus important to public health. In this study, a three-dimensional computational fluid dynamics model together with Eulerian and Lagrangian-based techniques are used for investigating the residence time characteristics of a passive tracer and particles in the water, representative of chemicals and pathogens, respectively. The flow pattern in the pool is found to be characterized by dead zone regions where water constituents may be retained for extended periods of times, thereby potentially decreasing the pool hydraulic efficiency. Two return-jet configurations are studied in order to understand the effect of return-jet location and intensity on the hydraulic efficiency of the pool. A two-jet configuration is found to perform on par with a three-jet configuration in removing dissolved constituents but the former is more efficient than the latter in removing or flushing particles. The latter result suggests that return-jet location and associated flow circulation pattern have an important impact on hydraulic efficiency. Thus return-jet configuration should be incorporated as a key parameter in the design of swimming pools complementing current design standards.


Assuntos
Piscinas , Purificação da Água/métodos , Desinfecção , Filtração , Hidrodinâmica , Natação
8.
Ecology ; 98(9): 2447-2455, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28632944

RESUMO

Animal distributions are influenced by variation in predation risk in space, which has been described as the "landscape of fear." Many studies suggest animals also reduce predation risk by eavesdropping on heterospecific alarm calls, allowing them to occupy otherwise risky habitats. One unexplored area of study is understanding how different species' alarms vary in quality, and how this variation is distributed in the landscape. We tested this phenomenon in a unique system of avian mixed species flocks in Amazonian rainforests: flock mates (eavesdropping species) strongly associate with alarm-calling antshrikes (genus Thamnomanes), which act as sentinel species. Up to 70 species join these flocks, presumably following antshrike behavioral cues. Since flocks in this region of the Amazon are exclusively led by a single antshrike species, this provides a unique natural system to compare differences in sentinel quality between flocks. We simulated predation threat by flying three species of live trained raptors (predators) towards flocks to compare sentinel probability to (1) produce alarm calls, and (2) encode information about magnitude and type of threat within such alarm calls. Our field experiments show significant differences in the probability of different sentinel species to produce alarm calls and distinguish predators. This variation may have important fitness consequences and shape the "landscape of fear" for eavesdropping species.


Assuntos
Passeriformes/fisiologia , Animais , Medo , Comportamento Predatório , Vocalização Animal
9.
Phys Chem Chem Phys ; 19(16): 10217-10221, 2017 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-28393951

RESUMO

The role of spin non-adiabatic effects in the reactivity of O2 on metal surfaces has been a matter of debate for several years. By means of density functional theory with a semi-local exchange-correlation functional, and classical dynamics calculations, we show that the recently observed activated character of O2 adsorption on Cu(111) and CuML/Ru(0001), as well as the delicate interplay between dissociative and non-dissociative O2 sticking on Cu(111) at different surface temperatures, can be explained by assuming an adiabatic evolution of the molecular spin. This suggests that spin adiabaticity during O2 adsorption on metal surfaces could be a more general scenario than anticipated.

11.
Int J Behav Med ; 24(2): 239-248, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27757840

RESUMO

PURPOSE: This study investigated the role of anxiety sensitivity, resilience, pain catastrophizing, depression, pain fear-avoidance beliefs, and pain intensity in patients with acute back pain-related disability. METHOD: Two hundred and thirty-two patients with acute back pain completed questionnaires on anxiety sensitivity, resilience, pain catastrophizing, fear-avoidance beliefs, depression, pain intensity, and disability. RESULTS: A structural equation modelling analysis revealed that anxiety sensitivity was associated with pain catastrophizing, and resilience was associated with lower levels of depression. Pain catastrophizing was positively associated with fear-avoidance beliefs and pain intensity. Depression was associated with fear-avoidance beliefs, but was not associated with pain intensity. Finally, catastrophizing, fear-avoidance beliefs, and pain intensity were positively and significantly associated with acute back pain-related disability. CONCLUSION: Although fear-avoidance beliefs and pain intensity were associated with disability, the results showed that pain catastrophizing was a central variable in the pain experience and had significant direct associations with disability when pain was acute. Anxiety sensitivity appeared to be an important antecedent of catastrophizing, whereas the influence of resilience on the acute back pain experience was limited to its relationship with depression.


Assuntos
Ansiedade/psicologia , Dor nas Costas/psicologia , Catastrofização/psicologia , Depressão/psicologia , Adulto , Estudos Transversais , Pessoas com Deficiência , Medo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Inquéritos e Questionários
12.
Br J Dermatol ; 174(1): 56-67, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26302137
18.
Br J Dermatol ; 171(4): 861-7, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24976116

RESUMO

BACKGROUND: Facial port-wine stains (PWSs) are usually isolated findings; however, when associated with cerebral and ocular vascular malformations they form part of the classical triad of Sturge-Weber syndrome (SWS). OBJECTIVES: To evaluate the associations between the phenotype of facial PWS and the diagnosis of SWS in a cohort with a high rate of SWS. METHODS: Records were reviewed of all 192 children with a facial PWS seen in 2011-13. Adverse outcome measures were clinical (seizures, abnormal neurodevelopment, glaucoma) and radiological [abnormal magnetic resonance imaging (MRI)], modelled by multivariate logistic regression. RESULTS: The best predictor of adverse outcomes was a PWS involving any part of the forehead, delineated at its inferior border by a line joining the outer canthus of the eye to the top of the ear, and including the upper eyelid. This involves all three divisions of the trigeminal nerve, but corresponds well to the embryonic vascular development of the face. Bilateral distribution was not an independently significant phenotypic feature. Abnormal MRI was a better predictor of all clinical adverse outcome measures than PWS distribution; however, for practical reasons guidelines based on clinical phenotype are proposed. CONCLUSIONS: Facial PWS distribution appears to follow the embryonic vasculature of the face, rather than the trigeminal nerve. We propose that children with a PWS on any part of the 'forehead' should have an urgent ophthalmology review and a brain MRI. A prospective study has been established to test the validity of these guidelines.


Assuntos
Mancha Vinho do Porto/classificação , Síndrome de Sturge-Weber/diagnóstico , Encefalopatias/etiologia , Criança , Deficiências do Desenvolvimento/etiologia , Feminino , Testa , Glaucoma/etiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Fenótipo , Fatores de Risco , Convulsões/etiologia , Doenças do Nervo Trigêmeo/etiologia
19.
Br J Dermatol ; 170(1): 196-9, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24443915

RESUMO

Several different genes have been implicated in the pathophysiology of inherited blistering skin diseases. Recently, autosomal recessive loss-of-function mutations in EXPH5 (encoding exophilin-5, also known as Slac2-b, a protein involved in intracellular vesicle transport) were identified in a new mechanobullous disease resembling a form of epidermolysis bullosa simplex (EBS). Here, we searched for mutations in EXPH5 in a 4-year-old white boy with EBS in whom initial Sanger sequencing of known genes implicated in intraepidermal skin fragility failed to identify pathogenic mutations. Transmission electron microscopy of rubbed nonlesional patient skin revealed disruption of keratinocytes in the lower epidermis with cytolysis and acantholysis, keratin filament clumping and prominent perinuclear cytoplasmic vesicles, and provided the clue to the candidate gene pathology. Sanger sequencing of genomic DNA showed compound heterozygosity for two new mutations in EXPH5, c.1947dupC (p.Pro649fsPro*11) and c.2249C>A (p.Ser750*). Immunofluorescence microscopy of patient skin showed a complete absence of exophilin-5 labelling. This case represents the third pedigree with EXPH5 mutations resulting in inherited skin fragility. The clinical and molecular data expand genotype-phenotype correlation in this new form of EBS and demonstrate the important role of exophilin-5 in keratinocyte cell biology.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Epidermólise Bolhosa Simples/genética , Mutação/genética , Pré-Escolar , Epidermólise Bolhosa Simples/patologia , Humanos , Queratinócitos/patologia , Masculino
20.
J Chem Phys ; 141(2): 024701, 2014 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-25028032

RESUMO

Dynamics of the Eley-Rideal (ER) abstraction of H2 from W(110) is analyzed by means of quasi-classical trajectory calculations. Simulations are based on two different molecule-surface potential energy surfaces (PES) constructed from Density Functional Theory results. One PES is obtained by fitting, using a Flexible Periodic London-Eyring-Polanyi-Sato (FPLEPS) functional form, and the other by interpolation through the corrugation reducing procedure (CRP). Then, the present study allows us to elucidate the ER dynamics sensitivity on the PES representation. Despite some sizable discrepancies between both H+H/W(110) PESs, the obtained projectile-energy dependence of the total ER cross sections are qualitatively very similar ensuring that the main physical ingredients are captured in both PES models. The obtained distributions of the final energy among the different molecular degrees of freedom barely depend on the PES model, being most likely determined by the reaction exothermicity. Therefore, a reasonably good agreement with the measured final vibrational state distribution is observed in spite of the pressure and material gaps between theoretical and experimental conditions.

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