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991.
Apremilast and suicidality – a retrospective analysis of three large databases: the FAERS,EudraVigilance and a large single‐centre US patient population 下载免费PDF全文
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The loss of function (LOF) due to mutations in the Filamin A (FLNA) gene may result in abnormality of the FLNA protein. Of the many clinical syndromes, this condition may produce chronic lung disease, which usually presents and is diagnosed in the infant/toddler age group. Its clinical pattern may mimic broncho-pulmonary dysplasia. It is part of the entities included in childhood interstitial lung disease group of disorders. We are herein reporting a patient that was diagnosed with FLNA-associated lung disease at 11 years of age. This case provides a unique insight into the long-term course of lung disease in this illness and broadens our understanding of the spectrum of its presentation. Although the patient had symptoms early in life, the diagnosis was not entertained because of the rarity of the disorder, its atypical and clinically mild presentation, and discontinuous care due to parents moving to different cities for employment reasons. Her presentation to our institution was for pneumonia. Due to highly unusual chest X-ray images, asthenia, and early clubbing, an extensive workup included further imaging and a lung biopsy. The final diagnosis was confirmed by the detection of FLNA LOF gene mutation. 相似文献
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Hussain Jaafari Lesley A. Houghton Robert M. West Anurag Agrawal Imran Aziz Christopher J. Black Maura Corsetti Farag Shuweihdi Maria Eugenicos Peter A. Paine Alexander C. Ford Peter J. Whorwell Shrikant I. Bangdiwala Olafur S. Palsson Ami D. Sperber Dipesh H. Vasant 《Neurogastroenterology and motility》2023,35(6):e14574
Background
There are minimal epidemiological data comparing the burden of disorders of gut brain interaction (DGBI) in the UK with other countries. We compared the prevalence of DGBI in the UK with other countries that participated in the Rome Foundation Global Epidemiology Study (RFGES) online.Methods
Participants from 26 countries completed the RFGES survey online including the Rome IV diagnostic questionnaire and an in-depth supplemental questionnaire with questions about dietary habits. UK sociodemographic and prevalence data were compared with the other 25 countries pooled together.Key Results
The proportion of participants with at least one DGBI was lower in UK participants compared with in the other 25 countries (37.6% 95% CI 35.5%–39.7% vs. 41.2%; 95% CI 40.8%–41.6%, p = 0.001). The UK prevalence of 14 of 22 Rome IV DGBI, including irritable bowel syndrome (4.3%) and functional dyspepsia (6.8%), was similar to the other countries. Fecal incontinence, opioid-induced constipation, chronic nausea and vomiting, and cannabinoid hyperemesis (p < 0.05) were more prevalent in the UK. Cyclic vomiting, functional constipation, unspecified functional bowel disorder, and proctalgia fugax (p < 0.05) were more prevalent in the other 25 countries. Diet in the UK population consisted of higher consumption of meat and milk (p < 0.001), and lower consumption of rice, fruit, eggs, tofu, pasta, vegetables/legumes, and fish (p < 0.001).Conclusions and Inferences
The prevalence and burden of DGBI is consistently high in the UK and in the rest of the world. Opioid prescribing, cultural, dietary, and lifestyle factors may contribute to differences in the prevalence of some DGBI between the UK and other countries. 相似文献998.
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West JA Chichester CH Buckpitt AR Tyler NK Brennan P Helton C Plopper CG 《American journal of respiratory cell and molecular biology》2000,23(1):27-36
Clara-cell populations show a high degree of variation in susceptibility to injury by bioactivated cytotoxicants. Because glutathione (GSH) is critical for detoxification of electrophilic metabolites, heterogeneity in Clara cell GSH levels may lead to a wide range of cytotoxic responses. This study was designed to define the distinct GSH pools within Clara cells, characterize heterogeneity within the population, and examine whether heterogeneity contributes to susceptibility. Using fluorescent imaging combined with high-performance liquid chromatography analysis, semiquantitative measurements were obtained by evaluation of GSH using monochlorobimane and monobromobimane. In steady-state conditions, the GSH measured in isolated cells was in the femtomole range, but varied 4-fold between individual cells. Clara cells analyzed in situ and in vitro confirmed this heterogeneity. The response of these cells to compounds that modulate GSH was also variable. Diethylmaleate depleted GSH, whereas GSH monoethylester augmented it. However, both acted nonuniformly in isolated Clara cells. The depletion of intracellular GSH caused a striking decrease in cell viability upon incubation with naphthalene (NA). The sulfhydryl-binding fluorochrome BODIPY, which colocalized with tetramethylrosamine, a mitochondrial dye, demonstrated by confocal microscopy that cellular sulfhydryls are highest in the mitochondria, next-highest in cytoplasm, and lowest in the nucleus. These pools responded differently to modulators of GSH. We concluded that the steady-state intracellular GSH of Clara cells exists in distinct pools and is highly heterogeneous within the population, and that the heterogeneity of GSH levels corresponds closely to the response of Clara cells to injury by NA. 相似文献