Biodistribution and kinetics of (131)I-labelled anti-CD20 MAB IDEC-C2B8 (rituximab) in relapsed non-Hodgkin's lymphoma

The native chimeric human-mouse anti-CD20 antibody IDEC-C2B8 (rituximab) is therapeutically applied in relapsed non-Hodgkin's lymphoma (NHL). The purpose of this study was to evaluate the distribution and pharmacokinetics of iodine-131 labelled rituximab in humans for radioimmunotherapy of relapsed CD20-positive NHL. Thirty-five patients with relapsed NHL were administered 20-40 mg rituximab labelled with 250 MBq (131)I. Biodistribution was determined by the gamma camera whole-body scans, whole-body probe measurements and the analysis of serial blood and urine samples. Dosimetry was performed using the MIRDOSE 3 program. Antibody administration was well tolerated. The whole-body activity showed a mono-exponential decrease with a wide range of effective half-lives, the mean value (88 h) being significantly longer than the half-life of its murine counterpart, tositumomab. This led to appropriately higher dose factors for the whole body and organs. Activity was excreted mainly through the kidneys. Normal organs showed decreasing ratios of organ to whole-body activity over time, whereas the tumour tissue presented different kinetics, with increasing ratios of tumour to whole-body activity as evidence for specific antibody binding. It is concluded that (131)I-labelled rituximab is suitable for pretherapeutic dosimetry. Due to the wide range of whole-body and organ dose factors, individual dosimetry is necessary for radioimmunotherapy with (131)I-labelled rituximab. The therapeutic activities of (131)I-labelled rituximab required to deliver similar doses should be lower than those of its murine counterpart.     

Postsurgical pain outcome of vertical and transverse abdominal incision: Design of a randomized controlled equivalence trial [ISRCTN60734227]

Background

There are two ways to open the abdominal cavity in elective general surgery: vertically or transversely. Various clinical studies and a meta-analysis have postulated that the transverse approach is superior to other approaches as regards complications. However, in a recent survey it was shown that 90 % of all abdominal incisions in visceral surgery are still vertical incisions. This discrepancy between existing recommendations of clinical trials and clinical practice could be explained by the lack of acceptance of these results due to a number of deficits in the study design and analysis, subsequent low internal validity, and therefore limited external generalisability. The objective of this study is to address the issue from the patient's perspective.

Methods

This is an intraoperatively randomized controlled observer and patient-blinded two-group parallel equivalence trial. The study setting is the Department of General-, Visceral-, Trauma Surgery and Outpatient Clinic of the University of Heidelberg, Medical School. A total of 172 patients of both genders, aged over 18 years who are scheduled for an elective abdominal operation and are eligible for either a transverse or vertical incision. To show equivalence of the two approaches or the superiority of one of them from the perspective of the patient, a primary endpoint is defined: the pain experienced by the patient (VAS 0–100) on day two after surgery and the amount of analgesic required (piritramide [mg/h]). A confidence interval approach will be used for analysis. A global α-Level of 0.05 and a power of 0.8 is guaranteed, resulting in a size of 86 patients for each group. Secondary endpoints are: time interval to open and close the abdomen, early-onset complications (frequency of burst abdomen, postoperative pulmonary complications, and wound infection) and late complications (frequency of incisional hernias). Different outcome variables will be ranked by patients and surgeons to assess the relevance of possible endpoints from the patients' and surgeons' perspective.

Conclusion

This is a randomized controlled observer and patient-blinded two-group parallel trial to answer the question if the transverse abdominal incision is equivalent to the vertical one due to the described endpoints.

     

TNF-α值与2型糖尿病胰岛素抵抗的关系

目的　探讨肿瘤坏死因子 -α(TNF -α)与 2型糖尿病胰岛素的关系。方法　用homa -R法选取有胰岛素抵抗 (IR组 )和无胰岛素抵抗 (NIR组 )的 2型糖尿病患者各 2 0例。另以 2 0名年龄及体重指数相匹配的人群的作为对照组 ,分别检测其空腹血糖、胰岛素 ,计算Homa -R值 ,用ELISA法检测TNF -α。结果　IR组的TNF -α与NIR组及对照组相比较明显增高 ,有统计学意义(P <0 0 5 ) ,IR组的空腹胰岛素水平及胰岛素抵抗指标Homa -R也显著高于NIR组及对照组 (P值为 <0 0 1) ,而三组间年龄、BMI、血脂、脂蛋白、血压均无显著性差异 (P >0 0 5 )。结论　血浆TNF -α水平与胰岛素抵抗呈密切相关 ,在 2型DM中有重要病理意义 ,可作为评估有无胰岛素抵抗的一项重要参考指标     

Hormone-induced refractoriness to mammary carcinogenesis in Wistar- Furth rats

One of the most consistent results in the epidemiology of human breast cancer is the inverse relationship of risk and early full-term parity. The goal of this study was to investigate the molecular mechanisms through which early full-term pregnancy protects the breast from cancer development. We used Wistar-Furth (WF) rats as our experimental system and mimicked pregnancy using estrogen and progesterone (E/P). Sexually mature female rats were treated with steroid hormones for 21 days and after 28 days of gland involution, the rats were administered MNU. Rats that received a high dose of 20 microg E and 20 mg P exhibited an 82% reduction in the incidence of mammary adenocarcinomas as compared to the rats receiving only blank pellets. Decreasing doses of E/P were partially protective suggesting that complete differentiation of the gland was not required for refractoriness. We measured the RNA expression levels of several target genes involved in the regulation of mammary cell proliferation and/or differentiation including estrogen receptor (ER) and progesterone receptor (PR), cyclins D1 and D2, the cell cycle inhibitors p16, p21 and p27, and the tumor suppressor p53. At the time of MNU treatment we found no significant differences in the expression of these genes, with the possible exception of p21, indicating that hormone treatment did not result in constitutive changes in expression levels. The numbers of apoptotic cells were low and comparable in the hormone exposed and age-matched virgin gland (AMV) at the time of carcinogen challenge and remained low for 8 days after MNU treatment. The number of BrdU-labeled cells at the time of carcinogen challenge were also low in both the AMV (1.8%) and hormone exposed (0.8%) animals. In contrast, cell proliferation in the AMV (5.7%) was significantly different from both the parous involuted (1.2%) and the E/P-treated involuted (1.5%) animals 8 days after MNU treatment. We interpret these data to indicate that hormone treatment results in mammary epithelial cells that have persistent alterations in intracellular pathways governing proliferation responses to carcinogens.      

Massive acroosteolysis in adult T-cell leukemia/lymphoma

Adult T-cell leukemia/lymphoma is a relatively uncommon disease, most often found in Japan, the Caribbean, the southeastern United States, and South America. To date there have been few reports of its skeletal manifestations. A case is reported in a 44-year-old man in which a short history of swelling of the hands and feet and painful motion in the fingers was followed by the rapid development of severe acroosteolysis.     

羟基磷灰石溶解度等温线的测定

目的：应用微量添加固体滴定和激光散射法测定HA(37℃)溶解度等温线。方法：滴定物为HA。半导体二极管激光为发射光源，散射光源探测器用于监测超过溶解平衡点出现的沉淀。微量添加固体滴定所引发的沉淀引起散射光源显著且恒定地高于基线，由此判断溶液已处于过饱和状态，该固体滴定总量用于代表溶解度等温线的数据点。结果：HA溶解度等温线(37℃)由6次滴定合共50个滴定终点构成。与传统方法所得结果比较，本实验所得HA的溶解度约为过往结果的百份之一。结论：微量添加固体滴定和激光散射法利于研究HA的溶解平衡且能得到准确的HA溶解度等温线。