The syndrome of T8 hyperlymphocytosis: variation in phenotype and cytotoxic activities of granular cells and evaluation of their role in associated neutropenia

We performed a longitudinal study of the phenotype and functions of granular lymphoid cells from seven patients with T8 hyperlymphocytosis and neutropenia. Whereas cells retained a T3+ T8+ (six cases) or T3- T8+ (one case) phenotype at different examinations, the expression of natural killer (NK)-related antigens (HNK1- and Leu11-defined antigens) exhibited striking variations, some of which were also observed after in vitro culture. Similarly, natural or antibody-mediated cytotoxic activities fluctuated in vivo and in vitro. Cells from the patient with T3- T8+ proliferation were able to inhibit directly the growth of early CFU-GM, CFU-E, and BFU-E and to a lesser extent of late CFU-GM, as shown by cultures of autologous blood or marrow progenitors after depletion (and subsequent addition) of granular cells. In the other six patients with T3+ T8+ cells, no such effect was found. However, after a 24-hour incubation of the progenitors with the granular cells, CFU-GM growth was clearly inhibited; this was not observed in all experiments, a finding which may be related to the spontaneous variations of cell killer functions. Finally, no correlation was noted between the clinical course or extent of lymphoid proliferation and cell function or phenotype or with the monoclonal (two cases), polyclonal (three cases) or germ-line (one case) patterns of T cell receptor beta gene configuration.     

Herbal hepatotoxicity:Challenges and pitfalls of causality assessment methods

The diagnosis of herbal hepatotoxicity or herb induced liver injury(HILI) represents a particular clinical and regulatory challenge with major pitfalls for the causality evaluation.At the day HILI is suspected in a patient,physicians should start assessing the quality of the used herbal product,optimizing the clinical data for completeness,and applying the Council for International Organizations of Medical Sciences(CIOMS) scale for initial causality assessment.This scale is structured,quantitative,liver specific,and validated for hepatotoxicity cases.Its items provide individual scores,which together yield causality levels of highly probable,probable,possible,unlikely,and excluded.After completion by additional information including raw data,this scale with all items should be reported to regulatory agencies and manufacturers for further evaluation.The CIOMS scale is preferred as tool for assessing causality in hepatotoxicity cases,compared to numerous other causality assessment methods,which are inferior on various grounds.Among these disputed methods are the Maria and Victorino scale,an insufficiently qualified,shortened version of the CIOMS scale,as well as various liver unspecific methods such as thead hoc causality approach,the Naranjo scale,the World Health Organization(WHO) method,and the Karch and Lasagna method.An expert panel is required for the Drug Induced Liver Injury Network method,the WHO method,and other approaches based on expert opinion,which provide retrospective analyses with a long delay and thereby prevent a timely assessment of the illness in question by the physician.In conclusion,HILI causality assessment is challenging and is best achieved by the liver specific CIOMS scale,avoiding pitfalls commonly observed with other approaches.     

A phase II study of 2-methoxyestradiol nanocrystal colloidal dispersion alone and in combination with sunitinib malate in patients with metastatic renal cell carcinoma progressing on sunitinib malate

Background Current treatment for metastatic renal cell cancer with vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKI) have provided improved overall survival, but complete responses are rare. We conducted a multicenter phase II study to evaluate the objective response rate of 2-methoxyestradiol (2ME2 NCD) alone and in combination with sunitinib for patients with metastatic renal cell carcinoma who have progressed on sunitinib alone. Methods Adults with metastatic kidney cancer were stratified depending on whether they were still taking sunitinib or had discontinued sunitinib therapy at the time of registration. Patients were treated with 2ME2 NCD alone or in combination with sunitinib. The primary endpoint was objective response rate. Results In total, 17 patients were enrolled, and 12 were evaluable for response (arm A, n = 7; arm b, n = 5). In arm A, four patients had the best response of stable disease, and three patients developed disease progression. In arm B, three patients had a best response of stable disease, and two patients had disease progression. One patient continued to receive treatment for a total of 14 cycles before developing disease progression. Fatigue was the most common observed toxicities. Thirty five percent of patients required discontinuation of therapy secondary to toxicities. Conclusions 2ME2 NCD had minimal anti-tumor activity, with no observed objective responses. The study was terminated because 2ME2 NCD was not found to be tolerable at the recommended phase 2 dose in this patient population. A newer 2ME2 analog is in development with a more favorable toxicity profile and increased potency.     

The role of the subgenual anterior cingulate cortex in dorsomedial prefrontal–amygdala neural circuitry during positive‐social emotion regulation

Positive‐social emotions mediate one's cognitive performance, mood, well‐being, and social bonds, and represent a critical variable within therapeutic settings. It has been shown that the upregulation of positive emotions in social situations is associated with increased top‐down signals that stem from the prefrontal cortices (PFC) which modulate bottom‐up emotional responses in the amygdala. However, it remains unclear if positive‐social emotion upregulation of the amygdala occurs directly through the dorsomedial PFC (dmPFC) or indirectly linking the bilateral amygdala with the dmPFC via the subgenual anterior cingulate cortex (sgACC), an area which typically serves as a gatekeeper between cognitive and emotion networks. We performed functional MRI (fMRI) experiments with and without effortful positive‐social emotion upregulation to demonstrate the functional architecture of a network involving the amygdala, the dmPFC, and the sgACC. We found that effortful positive‐social emotion upregulation was associated with an increase in top‐down connectivity from the dmPFC on the amygdala via both direct and indirect connections with the sgACC. Conversely, we found that emotion processes without effortful regulation increased network modulation by the sgACC and amygdala. We also found that more anxious individuals with a greater tendency to suppress emotions and intrusive thoughts, were likely to display decreased amygdala, dmPFC, and sgACC activity and stronger connectivity strength from the sgACC onto the left amygdala during effortful emotion upregulation. Analyzed brain network suggests a more general role of the sgACC in cognitive control and sheds light on neurobiological informed treatment interventions.     

微柱凝胶与聚凝胺交叉配血试验比较

1一般资料2004年受血者的血清标本,急诊受血者的血清标本用聚凝胺配血法进行交叉配血,其他受血者的血清标本用微柱凝胶配血卡进行交叉本配血,发现有阳性结果的标本再分别用微柱凝胶配血法和聚凝胺配血法进行测定.微柱凝胶配血法按照达亚美公司提供的微柱凝胶配血卡操作手册进行;聚凝胺配血法见<输血技术学>[1].在13 879例交叉配血试验中,这两种交叉试验共同出现阳性结果的有15例(表1).对这15份阳性标本用谱细胞进行抗体筛查,其中抗-c阳性的标本4例,抗-E阳性的标本4例,抗-e阳性的标本3例,抗-cE阳性的标本2例,抗-JKb阳性的标本1例,抗-Mia阳性的标本1例.     

胰头肿块型胰腺炎14例误诊分析

1临床资料1984-07/2004-03,我院收治慢性胰腺炎138例,其中肿块型49例,14例误诊为胰头癌而行手术治疗.男11例,女3例,年龄38~49(平均42)岁.     

Inhibition of Proinflammatory Biomarkers in THP1 Macrophages by Polyphenols Derived From Chamomile,Meadowsweet and Willow bark

Antiinflammatory compounds in the diet can alleviate excessive inflammation, a factor in the pathogenesis of common diseases such as rheumatoid arthritis, atherosclerosis and diabetes. This study examined three European herbs, chamomile (Matricaria chamomilla), meadowsweet (Filipendula ulmaria L.) and willow bark (Salix alba L.), which have been traditionally used to treat inflammation and their potential for use as antiinflammatory agents. Aqueous herbal extracts and isolated polyphenolic compounds (apigenin, quercetin and salicylic acid, 0–100 μM) were incubated with THP1 macrophages, and interleukin (IL)‐1β, IL‐6 and tumour necrosis factor‐alpha (TNF‐α) were measured. At concentrations of 10 μM, both apigenin and quercetin reduced IL‐6 significantly ( p < 0.05). Apigenin at 10 μM and quercetin at 25 μM reduced TNF‐α significantly ( p < 0.05). Amongst the herbal extracts, willow bark had the greatest antiinflammatory activity at reducing IL‐6 and TNF‐α production. This was followed by meadowsweet and then chamomile. The lowest effective antiinflammatory concentrations were noncytotoxic (MTT mitochondrial activity assay). The Comet assay, which was used to study the protective effect of the isolated phenols against oxidative damage, showed positive results for all three polyphenols. These are the first findings that demonstrate the antiinflammatory capacity of these herbal extracts. Copyright © 2012 John Wiley & Sons, Ltd.     

Early rectal tube removal for improved patient tolerance during double- contrast barium enema examination

During a five year period, 62 patients each underwent two barium enema examinations. The length of time that the rectal tube remained in place varied in each subject. Early rectal-tube removal resulted in better patient acceptance of the double-contrast barium enema examination.