A case of refractory vasculitic ulcers in a systemic lupus erythematosus patient responding to rituximab and hyperbaric oxygen therapy

Large refractory vasculitic ulcers are not commonly seen in systemic lupus erythematosus (SLE) patients. We report a case of refractory vasculitic ulcers responding to rituximab, a monoclonal antibody directed against CD20 cells leading to prolonged B cell depletion. This treatment was initiated after treatment with high‐dose steroids and other immunosuppressants were ineffective/associated with significant side‐effects. Following treatment with rituximab, there was sustained clinical improvement and subsequent reduction of prednisolone dose. Rituximab was well‐tolerated. Concomitant methotrexate therapy and hyperbaric oxygen therapy (HBOT) may have aided the recovery of the patient’s vasculitic ulcers. This case and anecdotal reports have illustrated the efficacy and safety of rituximab in the treatment of refractory SLE‐related vasculitic ulcers. Further studies to determine the long‐term efficacy and side‐effects would be useful.     

Acceptability and Efficacy of an Emollient Containing Ceramide-Precursor Lipids and Moisturizing Factors for Atopic Dermatitis in Pediatric Patients

Background

Atopic eczema or dermatitis (AD) is associated with atopy and is characterized by reduced skin hydration and an impaired skin barrier in the epidermis. We investigated the patient acceptability and efficacy of an emollient containing ceramide-precursor lipids and moisturizing factors (LMF) in AD.

Methods

Consecutive AD patients were recruited. Swabs and cultures were obtained from the right antecubital fossa and the worst-affected eczematous area, and disease severity [according to the SCORing Atopic Dermatitis (SCORAD) Index], skin hydration, and transepidermal water loss (TEWL) were measured prior to and after 2 weeks’ use of the LMF moisturizer. The general acceptability of treatment was documented as being ‘very good’, ‘good’, ‘fair’, or ‘poor’.

Results

Twenty-four AD patients [mean age 13.8 (standard deviation 5.7) years] were recruited. Two thirds of the patients reported very good or good acceptability of the LMF moisturizer, whereas one third reported fair or poor acceptability. There were no inter-group differences in the pre-use clinical parameters of age, objective SCORAD score, pruritus score, sleep disturbance score, skin hydration, TEWL, topical corticosteroid use, oral antihistamine use, or acceptability of previously used proprietary emollients. However, patients in the fair/poor acceptability group were more likely to have Staphylococcus aureus colonization and to be female (odds ratio 13, 95 % confidence interval 1.7–99.4; p = 0.021). Following use of the LMF moisturizer, the objective SCORAD score, pruritus score, and sleep disturbance score were lower in the very good/good acceptability group than in the fair/poor acceptability group. The mean objective SCORAD score improved (from 31.5 to 25.7; p = 0.039) and skin hydration improved [from 30.7 arbitrary units (a.u.) to 36.0 a.u.; p = 0.021] in the very good/good acceptability group. When the data were analyzed for the strength of the agreement of the rating of acceptability, the κ values were 0.338 (fair) for use of body wash and 0.118 (poor) for use of emollients before and after the trial.

Conclusion

The LMF moisturizer was considered acceptable by two thirds of the patients with AD. It seems that patients who found the moisturizer acceptable were less likely to be female or to be colonized by S. aureus before switching to the product, and they had less severe eczema, less pruritus, and less sleep disturbance after its use than patients who did not find the product acceptable. Gender and S. aureus colonization may have influenced the patient acceptability and clinical efficacy of the LMF moisturizer. The lack of agreement with regard to the acceptability of the moisturizer implies that there is room for parent/patient education to improve compliance.     

Phase 1 trial of ADI-PEG20 plus cisplatin in patients with pretreated metastatic melanoma or other advanced solid malignancies

Background Arginine depletion interferes with pyrimidine metabolism and DNA damage-repair pathways, and pairing arginine deiminase pegylated with 20,000-molecular-weight polyethylene glycol (ADI-PEG20) with platinum enhances cytotoxicity in vitro and in vivo in arginine auxotrophs.Methods This single-centre, Phase 1 trial was conducted using a 3 + 3 dose escalation designed to assess safety, tolerability and determine the recommended Phase 2 dose (RP2D) of ADI-PEG20.Results We enrolled 99 patients with metastatic argininosuccinate synthetase 1 (ASS1) deficient malignancies. We observed no dose-limiting toxic effects or treatment-related mortality. Three percent of patients discontinued treatment because of toxicity. After treatment, 5% (5/99) of patients had partial responses, and 41% had stable disease. The median progression-free and overall survival durations were 3.62 and 8.06 months, respectively. Substantial arginine depletion and citrulline escalation persisted in most patients through weeks 24 and 8, respectively. Tumour responses were associated with anti-ADI-PEG20 antibody levels at weeks 8 and 16 (p = 0.031 and p = 0.0357, respectively).Conclusion Concurrently administered ADI-PEG20 and cisplatin had an acceptable safety profile and had shown antitumour activity against metastatic ASS1-deficient solid tumours. Further evaluation of this treatment combination is warranted.Subject terms: Cancer, Cancer therapy     

大鼠海马与前皮质N4 mRNA神经元的发育--原位杂交与RT-PCR研究

目的 研究大鼠N4 mRNA神经元在前皮质与海马的时空表达模式。方法 地高辛标记的cRNA探针原位杂交组织化学和逆转录PCR技术。结果 E13-E16：原位杂交方法最早检测到N4 mRNA神经元，在海马与前皮质呈强阳性信号。P0～P2：N4 mRNA阳性信号在海马开始减弱，在前皮质仍维持较高的水平。P7：N4 mRNA阳性信号在海马明显减弱，仅在海马的齿状回见部分阳性神经元，在前皮质的水平轻度减低。P14：N4 mRNA神经元数目增多，主要位于海马齿状回的颗粒细胞层；P21-P28：N4 mRNA在海马的齿回呈强阳性信号，在CA3区呈中等程度的阳性信号，CA1区、CA2区及下托可见部分阳性神经元，前皮质可见Ⅱ／Ⅲ层的锥体细胞层呈强阳性信号。P90～P150：在海马的齿状回、CA3区，CA1区、CA2区及下托见中等强度的N4 mRNA阳性信号。P300：N4 mRNA神经元在海马与皮层的表达明显减少，仅见部分散在的阳性神经元。逆转录PCR检测结果与原位杂交所得结果基本相符，在胚胎期N4 mRNA表达最强，生后减弱，P7降至最低，P21～P28为生后的表达高峰，随之下降，P300表达弱。N4基因在不同发育时期皮层的表达，在胚胎期信号最强，生后略微减弱，组间差异不明显。结论 N4基因特异的表达于海马，并在海马的形成期表达最高，可能对海马的传入通路的发育有重要作用。     

一种基于FUZZYSET的尘肺治疗效果综合评价方法

本文提出的模型与方法，是基于ＦＵＺＺＹＳＥＴ构造一个多元函数，以此函数来判定、评价疗效。实践证明，该法对尘肺病疗效，有十分好的评价效果。该模型与方法可推广到其它医学领域的判定、评价中。