The effects of topical corticosteroids and a coal tar preparation on dithranol-induced irritation in patients with psoriasis

Dithranol has been a mainstay in the treatment of psoriasis for more than 80 years. Although a safe approach, the irritation of the clinically uninvolved perilesional skin remains a major limitation of this treatment. Corticosteroids and coal tar solution have an anti-inflammatory potential. The aim of the present study was to investigate the clinical and cell-biological effects of two topical corticosteroids and a coal tar preparation on dithranol-irritated skin. During 4 consecutive days, 2% dithranol cream was applied to six uninvolved skin sites (3 cm in diameter) on the lower back of 9 patients with psoriasis. Dithranol was left on the skin for 1 h, subsequently removed with water and soap and the skin was dried with a towel. Subsequently, SITE 1 was treated with 0.05% clobetasol-17-propionate ointment (CP), SITE 2 with unguentum cetomacrogolis (vehicle 1), SITE 3 with 0.005% fluticasonpropionate ointment (FP), SITE 4 with 10% coal tar solution in lanettewax cream (CTS), SITE 5 was left untreated (control) and SITE 6 was treated with lanettewax cream (vehicle 2). Erythema, oedema and vesicle formation was scored every day. On day 5, punch biopsies were taken from the six sites. The expression of epidermal proliferation, differentiation and inflammation markers and the clinical irritation scores indicate that the application of a high potency corticosteroid (CP) is the best approach to minimise dithranol irritation, whereas CTS had virtually no effect on dithranol irritation during this 4-day experimental model.     

Inhalational anesthetics inhibit spreading depression: relevance to migraine

Cortical spreading depression (SD) has not been shown in the human neocortex by direct cortical recordings. However, animal studies suggest that cortical injury, such as that occurring during neurosurgical procedures, should result in the initiation of SD. It is possible that inhibition of SD by volatile anesthetic agents may partially explain the failure to observe SD in the human neocortex during surgery. This study examines the effect of the anesthetic agents α-chloralose, halothane, nitrous oxide and isoflurane on the initiation of cortical SD in the cat neocortex. SD was seen in 100% of cats anesthetized with α-chloralose ( n = 15), in 3 of 7 (42%) animals anesthetized with isoflurane ( p < 0.05, χ² with Yates correction) and none of the animals ( n = 4, 6 hemispheric preparations) anesthetized with halothane ( p < 0.005, χ² with Yates correction, halothane vs α-chloralose group). In all cases this inhibitory effect was reversible. In four animals the administration of nitrous oxide (66%) reduced the inspired concentration of isoflurane required to inhibit SD by 0.75%. This study suggests that halothane, and to a lesser extent isoflurane and nitrous oxide, protect against the initiation of cortical SD. This observation may partially explain why SD has not been demonstrated in human neocortex during surgery. Further studies are needed to determine if SD may occur under pathological conditions, such as during migraine with aura, where the cortex may be predisposed to SD.     

Is fecundability associated with month of birth? An analysis of 19th and early 20th century family reconstitution data from The Netherlands

The relationship between fecundability and month of birth was investigated in a cohort of 1526 women who married between 1802 and 1929, using only women whose first marriage occurred before the age of 35 years. On the basis of their time to pregnancy (TTP, calculated as time between wedding and first birth minus gestational length), women were categorized into two groups: fecunds (TTP up to 12 months or prenuptial conceptions, n = 1348) and subfecunds (TTP >18 months, n = 118). By use of logistic regression, cosinor functions with a period of 1 year or 6 months and variable shift and amplitude were fitted through the monthly odds of subfecunds versus fecunds. The best fitting curve was unimodal, with a zenith in September (P = 0.13 for H0: no differences). Exclusion of childless women (n = 36, minimum follow-up 5 years) from the subfecunds led to a similar curve (P < 0.01), while childless women, as compared with fecunds, showed a birth distribution that was best represented with a bimodal curve with zeniths in January and July (P = 0.06). This study provides evidence for the existence of differences in fecundability by month of birth. The cause of this relationship is unclear, but may lie in a melatonin-dependent circannual variability of the quality of the oocyte.      

Grading of dysplasia in Barrett's oesophagus: substantial interobserver variation between general and gastrointestinal pathologists

AIMS: To determine interobserver variation in grading of dysplasia in Barrett's oesophagus (BO) between non-expert general pathologists and expert gastrointestinal pathologists on the one hand and between expert pathologists on the other hand. METHODS AND RESULTS: In this prospective multicentre study, non-expert and expert pathologists graded biopsy specimens of 920 patients with endoscopic BO, which were blindly reviewed by one member of a panel of expert pathologists (panel experts) and by a second panel expert in case of disagreement on dysplasia grade. Agreement between two of three pathologists was established as the final diagnosis. Analysis was performed by kappa statistics. Due to absence of intestinal metaplasia, 127/920 (14%) patients were excluded. The interobserver agreement for dysplasia [no dysplasia (ND) versus indefinite for dysplasia/low-grade dysplasia (IND/LGD) versus high-grade dysplasia (HGD)/adenocarcinoma (AC)] between non-experts and first panel experts and between initial experts and first panel experts was fair (kappa = 0.24 and kappa = 0.27, respectively), and substantial for differentiation of HGD/AC from ND/IND/LGD (kappa = 0.62 and kappa = 0.58, respectively). CONCLUSIONS: There was considerable interobserver variability in the interpretation of ND or IND/LGD in BO between non-experts and experts, but also between expert pathologists. This suggests that less subjective markers are needed to determine the risk of developing AC in BO.     

PCT、CRP动力学评估脓毒血症预后及诊断意义的研究

目的 观察血清降钙素原(PCT)、C反应蛋白(CRP)及其动力学变化,评估其在严重脓毒症/感染性休克患者的诊断及预后价值.方法 本研究采用回顾性分析方法,2014年9月1日至2016年4月30日选择184例ICU中被诊断为严重脓毒症/感染性休克疾病患者,检测入院时血清PCT、CRP水平和治疗后第2,第3和第5天的PCT、CRP水平.结果 通过△PCT、△CRP评估PCT、CRP的动力学在存活者与死亡组中有显著性统计学意(△PCT2/0,P=0.0001;△PCT3/0,P=0.0001;△PCT5/0,P=0.0001;△CRP2/0,P=0.0069;△CRP3/0,P=0.0001;△CRP5/0,P=0.0001),在严重脓毒症和感染性休克组中也存在显著差异(PCT5,P=0.007;△PCT5/0,P=0.007).受试者工作特征曲线(ROC)模型显示,△PCT3/0(AUC=0.721)、△PCT5/0(AUC=0.77)、△CRP5/0(AUC=0.766)水平判断严重脓毒症/感染性休克患者预后有较好的临床意义.△PCT5/0 (0.619)对严重脓毒症或感染性休克有一定的辅助诊断效果,其在ROC曲线上灵敏度、特异性均较高的临界点为0.624,所以,以第5天的血清△PCT5/0水平＞0.624可作为预测感染性休克的临界点.结论 血清中PCT、CRP对严重脓毒症/感染性休克早期有较好的临床诊断及预后价值,其动力学研究可以提高对严重脓毒症/感染性休克诊断及预后评估的敏感性及准确性.     

Low-density lipoprotein receptor gene mutations in a Southeast Asian population with familial hypercholesterolemia

The aim of this study was to detect mutations in the genes coding for the low-density lipoprotein receptor and apolipoprotein B in patients of Southeast Asian origin with clinically diagnosed familial hypercholesterolemia (FH) and to relate these findings with the observed lower incidence of coronary heart disease in this part of the world. A total of 86 unrelated patients with FH were selected on clinical grounds, and complete DNA analysis of the low-density lipoprotein (LDL)-receptor and apolipoprotein B (apoB) genes by DGGE and DNA-sequencing was performed. In the majority (73%) of the cohort studied, no mutations could be detected, even after extensive analysis of the LDL-receptor and apoB genes. However, the 22 patients with a mutation had significantly more xanthomas and a higher incidence of coronary heart disease and levels of low-density lipoproteins were also significantly different. There was no correlation between the type of the mutation and lipoprotein levels or clinical signs of atherosclerosis. The fact that the majority of the FH patients studied had no detectable mutation and that this group had a significant milder phenotype, suggests the presence of a third gene in the Southeast Asian population, predominantly leading to a disorder resembling a milder form of FH. A similar, but less frequent, trait has recently been described in a number of European families.     

Unbearability of suffering at the end of life: the development of a new measuring device, the SOS-V

Background  

Unbearable suffering is an important issue in end-of-life decisions. However, there has been no systematic, prospective, patient-oriented research which has focused on unbearable suffering, nor is there a suitable measurement instrument. This article describes the methodological development of a quantitative instrument to measure the nature and intensity of unbearable suffering, practical aspects of its use in end-stage cancer patients in general practice, and studies content validity and psychometric properties.     

Cognitive, behavioral, and physiological reactivity to chronic itching: Analogies to chronic pain

It is well-known that cognitive, behavioral, and physiological reactivity to pain, such as catastrophizing, avoidance of activity, and increased physiological responses, can unfavorably affect long-term outcomes in patients with chronic pain. In line with similarities between the psychophysiology of pain and itching, corresponding mechanisms may be relevant for the maintenance of chronic itching. The goal of this study was to examine the role of self-reported cognitive, behavioral, and physiological reactivity factors on itching-related outcomes in 235 patients with chronic skin diseases suffering from chronic itching. Sequential regression analyses indicate that all 3 reactivity systems predicted itching-related outcomes. Specifically, more catastrophizing, higher levels of avoidance of activity, and heightened self-reported physiological reactivity predicted more itching, more scratching, and a reduced disease-related quality of life. The results suggest that a psychological model as described for chronic pain is a useful starting point for study of the maintaining mechanisms of chronic itching.     

藏羚羊和藏系绵羊左心室收缩功能的比较研究

目的:探讨藏羚羊适应高原低氧环境的左心功能特点。方法:捕捉海拔4 300 m藏羚羊9只、藏系绵羊10只运至格尔木(海拔2 800 m)实验基地。测定二者的心脏/体重比(HW/BW)、右心室/(左心室+室间隔)重量比[RV/(LV+IVS)];应用心导管技术测定心率(HR)、收缩压(SBP)、舒张压(DBP)、左室等容收缩期心室内压力上升最大速率和左室等容舒张期心室内压力下降最大速率(±dp/dt)。以格尔木市的氧浓度(21.1%)为基线,分别给予更低浓度氧14.6%、12.5%(分别相当于海拔5 300 m、6 300 m)的低氧吸入15 min后重复测定以上指标。应用透射电镜观察心肌超微结构。结果:藏羚羊HW/BW显著高于藏系绵羊(P0.01),基础状态下藏羚羊SBP低于藏系绵羊(P0.05),+dp/dt与藏系绵羊比无显著差异,吸入14.6%和12.5%的低氧气体后藏羚羊+dp/dt分别升高至145.1%和148.1%,而藏系绵羊分别降低至68.4%和70.5%(P0.05);电镜下观察藏羚羊心肌超微结构与藏系绵羊比较,其心肌细胞线粒体较为丰富。结论:藏羚羊心脏对高海拔低氧环境的适应,是通过增加心脏器官的重量及心肌细胞线粒体的含量来实现,其心肌收缩功能的适应性特征为:在静息状态下以较低的左心室心肌收缩力来降低氧耗量以此适应高原低氧环境,而以海拔更高的较低氧浓度为应激条件下,左心室心肌收缩力明显升高。提示:藏羚羊作为高原适应性动物,经过漫长的自然选择其心脏对高原低氧环境的适应不同于藏系绵羊。     

红景天抑制人脐静脉内皮细胞生长的初步研究

目的:利用体外培养人脐静脉内皮细胞,观察中药红景天对细胞生长的影响,初步探讨急、慢性高原病患者服用中药红景天防治高原病及改善症状等的作用机制。方法:培养人脐静脉内皮细胞EVC-304,设对照组与加药组,加药组分别加入不同浓度的红景天,培养3d后计数。加药组及对照组细胞用瑞氏染料染色并拍照。收集细胞以流式细胞术检测细胞周期。结果:对照组细胞形态正常,成梭形,排列紧密,分散均匀。加药组细胞数量明显减少,细胞皱缩,聚集成团,形态各异。流式细胞术检测显示加药组G1期细胞含量增多,S期细胞减少。结论:红景天具有抑制血管内皮细胞生长的作用,可能是通过抑制细胞的增殖来抑制内皮细胞生长。抑制血管内皮细胞生长对于阻止血管内膜增生,防止形成肺动脉高压,降低慢性高原病发病率具有实际应用意义。