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Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

Objectives

To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions.

Methods

Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by β-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections.

Results

Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers.

Conclusions

These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study.  相似文献   
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Context

Family caregivers constitute a critical component of the end-of-life care system with considerable cost to themselves. However, the joint association of terminally ill cancer patients' symptom distress and functional impairment with caregivers' subjective caregiving burden, quality of life (QOL), and depressive symptoms remains unknown.

Objectives/Methods

We used multivariate hierarchical linear modeling to simultaneously evaluate associations between five distinct patterns of conjoint symptom distress and functional impairment (symptom-functional states) and subjective caregiving burden, QOL, and depressive symptoms in a convenience sample of 215 family caregiver–patient dyads. Data were collected every 2 to 4 weeks over patients' last 6 months.

Results

Caregivers of patients in the worst symptom-functional states (States 3–5) reported worse subjective caregiving burden and depressive symptoms than those in the best two states, but the three outcomes did not differ between caregivers of patients in State 3 and States 4–5. Caregivers of patients in State 5 endured worse subjective caregiving burden and QOL than those in State 4. Caregivers of patients in State 4 suffered worse subjective caregiving burden and depressive symptoms but comparable QOL to those in State 2.

Conclusion

Patients' five distinct, conjoint symptom-functional states were significantly and differentially associated with their caregivers' worse subjective caregiving burden, QOL, and depressive symptoms while caring for patients over their last 6 months.  相似文献   
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BACKGROUND/PURPOSE: The importance of accurate triage in Taiwan is becoming more apparent with the increasing number of emergency department (ED) patients, and resources for the National Health Insurance becoming constrained. This study compared the ability of the Taiwan triage system (TTS) and the standardized 5-level Emergency Severity Index (ESI) triage system to predict ED resource utilization. METHODS: Patients arriving at the ED were triaged by both TTS and by using a two-page checklist of ESI criteria during the 3-month study period. The ESI triage level was calculated independently to avoid bias. Disease category (trauma vs. nontrauma), length of stay (LOS) and hospitalization data were evaluated. RESULTS: A total of 3172 patients with both ESI and TWN evaluation were included. The distributions of ESI ratings within TTS level 1 were: ESI 1, 21.1%; ESI 2, 68.1%; ESI 3, 7.4%; ESI 4, 3.4%; ESI 5, 0%. For TTS level 3, they were: ESI 1, 0.1%; ESI 2, 26.2%; ESI 3, 39.5%; ESI 4, 27.5%; ESI 5, 6.8%. Hospitalization rates were 74.5%, 40.9% and 22.2% in TTS levels 1, 2 and 3, respectively; and were 96.2%, 47.0%, 30.9%, 6.7%and 6.6% in ESI levels 1, 2, 3, 4 and 5, respectively. TTS triaged more trauma patients as life-threatening/emergent condition than nontrauma patients (68.8% vs. 48.4%, p < 0.001). Triage by ESI, however, showed no significant difference in the percentage of trauma and nontrauma patients with highly acute conditions (44.2% vs. 46.6%, p = 0.230). Patients with ESI level 4 or 5 have significantly shorter ED LOS than those with ESI level 3. CONCLUSION: ESI produces more accurate discriminating patient acuity, ED LOS and hospitalization rate than TTS. Adopting a standardized 5-level triage tool might improve resource utilization planning of ED practice.  相似文献   
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Alpha-Melanocyte-stimulating hormone (MSH) is a potent anti-inflammatory agent in many models of inflammation, suggesting that it inhibits a critical step common to different forms of inflammation. We showed previously that alpha-MSH inhibits nitric oxide (NO) production in cultured macro-phages. To determine how alpha-MSH acts in vivo, we induced acute hepatic inflammation by administering endotoxin (LPS) to mice pretreated with Corynebacterium parvum, alpha-MSH prevented liver inflammation even when given 30 min after LPS administration. To determine the mechanisms of action of alpha-MSH, we tested its influence on NO, infiltrating inflammatory cells, cytokines, and chemokines. Alpha-MSH inhibited systemic NO production, hepatic neutrophil infiltration, and increased hepatic mRNA abundance for TNF alpha, and the neutrophil and monocyte chemokines (KC/IL-8 and MCP-1). We conclude that alpha-MSH prevents LPS-induced hepatic inflammation by inhibiting production of chemoattractant chemokines which then modulate infiltration of inflammatory cells. Thus, alpha-MSH has an effect very early in the inflammatory cascade.  相似文献   
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目的:了解腮腺非霍奇金淋巴瘤与舍格伦综合征的临床及发病机制的相关性,正确诊断和治疗舍格伦综合征,尽早明确有无恶性变。方法:对142例口腔颌面部的非霍奇金淋巴瘤中21例发生在腮腺的非霍奇金淋巴瘤,及3例从合格伦综合征演变成淋巴瘤的病例进行分析。结果:21例腮腺区非霍奇金淋巴瘤的局部表现主要为肿块、反复肿胀,与类肿瘤型舍格伦综合征的一般特征和腮腺表现有相关性,其中3例腮腺淋巴瘤患者有明确的舍格伦综合征病史。结论:舍格伦综合征与腮腺非霍奇金淋巴瘤的发生发展,以及临床表现有相关性,部分类肿瘤型舍格伦综合征可演变为淋巴瘤,临床表现和免疫学改变可早期判断舍格伦综合征有无恶性变。  相似文献   
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