Effects of monoclonal antibody therapy in patients with chronic lymphocytic leukemia

A phase I clinical trial was initiated to treat patients with stage IV B-derived chronic lymphocytic leukemia (CLL) with the IgG2a murine monoclonal antibody T101. This antibody binds to a 65,000-mol wt (T65) antigen found on normal T lymphocytes, malignant T lymphocytes, and B- derived CLL cells. All of the patients had a histologically confirmed diagnosis of advanced B-derived CLL and were refractory to standard therapy, and more than 50% of their leukemia cells reacted with the T101 antibody in vitro. The patients received T101 antibody two times per week, over two to 50 hours by intravenous administration in 100 mL of normal saline containing 5% human albumin. Twelve patients were treated with a fixed dosage of 1, 10, 50, or 100 mg, and one patient was treated with 140 mg of antibody. It was demonstrated that patients given two-hour infusions of 50 mg developed pulmonary toxicity, with shortness of breath and chest tightness. This toxicity was eliminated when infusions of 50 or 100 mg of T101 were prolonged to 50 hours. All dose levels caused a rapid but transient decrease in circulating leukemia cell counts. In vivo binding to circulating and bone marrow leukemia cells was demonstrated at all dose levels with increased binding at higher dosages. Antimurine antibody responses were not demonstrated in any patients at any time during treatment. Circulating free murine antibody was demonstrated in the serum of only the two patients treated with 100 mg of antibody as a 50-hour infusion and the patient treated with 140 mg of antibody over 30 hours. Antigenic modulation was demonstrated in patients treated at all dose levels but was particularly apparent in patients treated with prolonged infusions of 50 and 100 mg of antibody. We were also able to demonstrate antigenic modulation in lymph node cells, which strongly suggests in vivo labeling of these cells. Overall, T101 antibody alone appears to have a very limited therapeutic value for patients with CLL. The observations of in vivo labeling of tumor cells, antigenic modulation, antibody pharmacokinetics, toxicity, and antimurine antibody formation may be used in the future for more effective therapy when drugs or toxins are conjugated to the antibody.     

Urine biomarkers for monitoring juvenile lupus nephritis: a prospective longitudinal study

Background

In juvenile-onset systemic lupus erythematosus (JSLE), renal involvement (lupus nephritis) is frequently seen and can result in long-term morbidity. This prospective longitudinal study aimed to identify the utility of standard and/or novel biomarkers for monitoring and predicting lupus nephritis in a real world setting.

Methods

Using an unselected JSLE cohort, urine samples were collected during routine clinical review. Protein concentrations of urinary monocyte chemo-attractant protein 1 (uMCP1) and neutrophil gelatinase-associated lipocalin (uNGAL) were analysed along with standard disease activity markers, and were compared with current and subsequent disease activity.

Results

JSLE patients (n?=?64; median age 14.1 years) were seen at 3 (interquartile range: 2–5) clinical reviews over 364 (182–532) days. Multivariate analysis demonstrated uMCP1 and serum C3 as independent variables (p?<?0.001) for active renal disease at the time of the current review. uMCP1 was an excellent predictor of improved renal disease over time (AUC: 0.81; p?=?0.013). uNGAL was a good predictor of worsened renal disease activity (AUC 0.76; p?=?0.04) over time.

Conclusion

Biomarkers (uMCP1, serum C3) can indicate current renal involvement in JSLE, whilst uMCP1 and uNGAL are able to predict subsequent renal disease activity changes. Moving towards biomarker-led monitoring may improve the renal outcome for our patients.     

The use of bisphosphonates in children: review of the literature and guidelines for dental management

Bisphosphonates are inhibitors of osteoclastic bone resorption with therapeutic benefit in a variety of bone disorders in both adults and children. While these agents have been routinely used in adults for the past three decades, their more recent introduction into paediatric medicine means there is a paucity of data on long‐term safety and effects on dental development. There is uncertainty regarding the dental management of children treated with bisphosphonates, particularly when invasive dental procedures, such as extractions and oral surgical procedures, are required. There are limited data with which to make recommendations about the dental management of patients treated with bisphosphonates, and there are no published recommendations that specifically address paediatric patients. This paper aims to outline paediatric uses and adverse effects of bisphosphonates and present recommendations on the dental management of children receiving bisphosphonates.     

基于层次分析法（AHP）的保健食品原料评价体系构建及分析

目的建立保健食品原料评价体系(Functional Food Crude Materials Evaluation System,FUFMES),为保健食品原料目录排名提供科学依据与技术保障。方法首先,利用文献调研和多轮专家访谈方法筛选FUFMES的指标并确定其层级关系;第二,使用层次分析法(Analytic Hierarchy Process,AHP)计算指标权重,具体方法是依据专家打分构建判断矩阵,利用R语言进行一致性检验与最大特征根检验,得出各级指标权重;第三,使用极值法计算原料的单个指标值;第四,利用线性加权综合法得到每种原料的评价指数并据此进行排名;最后,将获得的分析结果与专家评价结果进行比较。结果 FUFMES包括6个一级指标、39个二级指标、11个三级指标。利用FUFMES对9种保健食品原料进行评价,获得的评价指数依次是:西洋参(0.49)、人参(0.48)、银杏叶(0.21)、灵芝孢子粉(0.08)、鱼油(0.06)、螺旋藻(0.03)、辅酶Q10(0.02)、褪黑素(0.01)、大蒜油(-0.03)。基于该评价指数的排名结果与专家评价结果显示了较高一致性。结论构建了科学、完整的FUFMES,FUFMES将成为保健食品原料目录评价与排名的有力工具,为推进保健食品原料备案制提供科学依据与技术保障。     

家庭雾化吸入治疗反复喘息患儿疗效观察

目的探讨家庭雾化吸入治疗反复喘息患儿的疗效。方法前瞻性分析2012-2013年住院治疗的反复喘息患儿316例,按照是否进行家庭雾化规范治疗分为家庭雾化吸入组和非家庭雾化吸入组。观察家庭雾化吸入治疗反复喘息患儿,能否降低再次住院率、应用全身糖皮质激素及抗生素使用率。结果家庭雾化吸入组198例,随访1年当中其再次住院率为20.2%,门急诊就诊率为66.6%,应用全身糖皮质激素16.6%,应用抗生素65.6%,有症状天数14±5.2天,明显低于非家庭雾化吸入组,差异有统计学意义(P0.05),而两组间一年的医疗费用无统计学差异(P0.05)。结论家庭雾化吸入治疗,可降低反复喘息患儿再次住院率、门急诊就诊率、有症状天数及应用全身糖皮质激素、抗生素治疗次数而一年的医疗费用无增加。     

羊肚菌属群体遗传学和基因组进化的研究进展

羊肚菌Morchella esculenta是子囊菌亚门的一种大型药食两用真菌,具有重要的经济价值和药用价值。然而近年来全球气候变化,导致羊肚菌属物种的栖息地破碎和片段化,加上消费者对羊肚菌美食的喜爱,过渡采挖造成羊肚菌属野生资源急剧减少,因此,急需对羊肚菌属物种资源进行保护。遗传多样性的时空分布是保护生物学的重要内容,遗传多样性关系到一个物种或类群的进化潜力和未来命运。生物基因组和进化的研究能够辅助挖掘物种深层次的优异基因资源,有利于从本质上对物种进行科学保护。从羊肚菌属的遗传多样性、遗传结构和家系关系以及基因组进化等的研究进展进行综述,以期为羊肚菌属资源的科学保护提供重要依据。     

浅谈中西医结合治疗癌性疼痛

癌性疼痛是肿瘤最为常见的临床症状之一,如何有效地控制癌性疼痛,改善癌症病人的生活质量,延长生存期已成为全球关注的焦点。WHO调查认为:进展期癌症和终末期癌症病人约75%～90%以疼痛为主要临床症状,经过治疗90%的癌性疼痛可缓解。单纯运用西医的三阶梯镇痛疗法会导致病人药物成瘾性及较大的毒副作用;而单纯运用中医药疗法止痛效果不甚显著。因此,将中西医疗法结合运用到治疗癌性疼痛上,将成为今后癌症病人综合治疗的重要环节,尤其近年来中医学以其独特的理论体系,辨病辨证相结合,采用中药内服、外用、针灸等方法,对癌性疼痛的治疗研究取得了满意的进展。