树突状细胞在慢性乙型肝炎和肝癌治疗中的应用前景

目的:综述树突状细胞在慢性乙型肝炎和肝癌治疗中的应用前景。资料来源:应用计算机检索PUBMED2001-01/2005-12期间的相关文章,检索词为"dendritic cells,chronic type B hepatitis,hepatoma,therapy",并限定文章语言种类为English。同时计算机检索万方数据库2001-01/2005-12期间的相关文章,检索词为"树突状细胞,慢性乙肝,肝癌,治疗",并限定文章语言种类为中文。资料选择:对资料进行初审,并查看每篇文献后的引文。纳入标准:文章所述内容应与树突状细胞在慢性乙型肝炎和肝癌治疗中的应用相关。排除标准:重复研究或Meta分析类文章。资料提炼:共收集到56篇相关文献,30篇文献符合纳入标准,排除的26篇文献为内容陈旧或重复。符合纳入标准的30篇文献中,15篇涉及树突状细胞与慢性乙型肝炎的治疗,10篇涉及树突状细胞与肝癌的治疗,5篇涉及存在的问题与展望。资料综合:慢性乙型肝炎和肝癌的发生发展与病毒的持续感染和机体的免疫功能障碍有关,树突状细胞是机体中功能最强的抗原提呈细胞,在诱导T细胞抗病毒和抗肿瘤免疫中起核心作用。①树突状细胞与慢性乙型肝炎的治疗:许多证据表明由树突状细胞介导的细胞毒T淋巴细胞反应,通过杀伤感染的肝细胞和释放抗病毒的细胞因子来清除乙型肝炎病毒。②树突状细胞与肝癌的治疗:研究证明,经肿瘤抗原致敏的树突状细胞能明显增强特异性细胞毒T淋巴细胞对肝癌细胞的杀伤活性。结论:树突状细胞与慢性乙型肝炎和肝癌的发生发展密切相关。在乙型肝炎和肝癌治疗中,如能激发、增强机体对乙型肝炎病毒和肝癌细胞的主动免疫排斥反应,可有助于清除体内的病毒和肿瘤,达到抗病毒和抗肿瘤治疗的目的。     

神经传导速度测定对糖尿病合并肘管综合征的诊断意义

目的对糖尿病并发肘管综合征患者的神经传导速度测定结果进行分析。方法对85例糖尿病患者行神经传导速度及肌电图检测,统计糖尿病周围神经损害及肘管综合征的比率。结果 85例患者中周围神经损害36例,符合肘管综合征诊断11例(12.9%),其中糖尿病周围神经损害合并肘管综合征7例,单纯肘管综合征4例,双侧均有损害的3例。肘管综合征表现为肘下-肘上运动神经传导速度减慢(同上臂比较>10m/s),并有腕—小指感觉神经电位波幅降低8例,肘下-肘上运动电位波幅降低(>50%)伴小指展肌、第一骨间肌出现自发电位3例。结论糖尿病患者中并发肘管综合征的患者并不少见,可能存在卡压机制,并且神经传导速度测定可以及早发现糖尿病并发的肘管综合征,使患者能及时得到治疗。     

Valproic acid pharmacokinetics in children: III. Very high dosage requirements

Nine children were studied who required very high doses of valproic acid (VPA) (63.6-105 mg/kg/day) in order to achieve VPA serum concentrations between 50-100 micrograms/ml. These nine children had poorly controlled seizures and were receiving other antiepileptic drugs at the time of this study. The children with very high dose requirements were significantly lighter, shorter, and had less body surface area than the control group. Of the pharmacokinetic parameters studied, total and intrinsic clearance, distribution volume, and valproic acid free fraction were significantly increased in the very high dose group. In three patients who were investigated after co-medications were eliminated, clearances and dosage requirements decreased by more than 50%. We concluded that very high VPA dosages are sometimes required to achieve therapeutic serum drug concentrations and that this therapy occasionally improves seizure control. There were no adverse effects of very high dose therapy that required dosage reduction.     

Randomized, double-blind, placebo-controlled, phase III study of recombinant human granulocyte-macrophage colony-stimulating factor as adjunct to induction treatment of high-grade malignant non-Hodgkin's lymphomas [see comments]

We evaluated recombinant human granulocyte-macrophage colony- stimulating factor (rhGM-CSF; Sandoz Pharma [Basel, Switzerland]/Schering-Plough [Kenilworth, NJ]) as an adjunct to a modified (mainly cyclophosphamide and doxorubicin increased 1.5-fold) COP-BLAM regimen in the primary treatment of high-grade malignant non- Hodgkin's lymphomas (NHL). Patients (n = 182; stage II-IV; age, 15 to 73 years) were randomized to rhGM-CSF (400 micrograms) or placebo for 7 days subcutaneously after chemotherapy. Efficacy was analyzed for patients receiving at least 70% of study medication (n = 125). The frequency of clinically relevant infection was reduced by rhGM-CSF (28 v 69 infections, 16 v 30 patients, P = .02) with a cumulative probability of remaining infection free in 70% versus 48% (P = .05 log rank test at 190 days). Periods of neutropenia (P = .01 in 5 of 6 courses), days with fever (2.1 v 4.0, P = .04) and days of hospitalization for infection (3.5 v 8.0 days, P = .01) were significantly reduced. Complete response (CR) rates, assessed by prognostic risk, were 15 of 19 (79%) in treated versus 20 of 21 (95%) in controls in the low-risk group (P = .12). In the high-risk group, 31 of 45 (69%) treated patients achieved CR versus 25 of 52 (48%) of controls (P = .04). No difference in survival has been seen after 1 year. Only injection site reactions (45% treated v 7% controls) and rash (26% v 2%) occurred more frequently in treated patients (n = 176). These data show that rhGM-CSF is well tolerated in most patients with NHL, significantly reduces infection, and improves response.     

Colorectal carcinoma: detection with indium-111 anticarcinoembryonic- antigen monoclonal antibody ZCE-025

A phase I and II clinical trial with indium-111-labeled anticarcinoembryonic-antigen monoclonal antibody ZCE-025 (In-111 ZCE-025) was initiated. Fifteen patients with colorectal tumors underwent external scintigraphy following the administration of 5.5 mCi (203.5 MBq) In-111 ZCE-025 at doses of 2.5-80.0 mg. Eighteen of 20 documented tumor sites, excluding those in the liver, were detected with In-111 ZCE-025. Lesions less than 1.5 cm could not be detected. Twenty-five percent of liver metastases exhibited positive accumulation of In-111 ZCE-025 at doses of 40-80 mg. No side effects were encountered. Because of the high detection rate of lymph node metastases from colorectal carcinoma with In-111 ZCE-025, this technique may be helpful in preoperative staging of patients with colorectal tumors, as well as in distinguishing recurrent tumors from postoperative or postradiation changes seen on computed tomography scans or other radiologic images.     

Late improvements in mobility after acquired brain injuries in children

The purpose of this investigation was to describe the late improvements in functional mobility in children who have sustained severe acquired anoxic or traumatic brain injuries. Ninety-eight children from a consecutive series of 199 with acquired brain injuries met inclusion criteria. As expected, children with traumatic injuries had better mobility at time of discharge from rehabilitation than did children with anoxic injury. In addition, children with traumatic injuries improved more in mobility status during the first 2 years after injury than did children with anoxic injury. The children who continued to improve in mobility after discharge were unconscious for a shorter time. Children who became community ambulators during the first year after discharge had higher mobility ratings at discharge. Although children who eventually achieved more functional mobility were admitted to rehabilitation service sooner after injury, discriminant analysis revealed that the duration of unconsciousness, and therefore severity of injury, was more closely correlated with the final mobility status.     

Reactive angioendotheliomatosis: is it ‘intravascular histiocytosis’?

We report the case of a 68-year-old female with reactive angioendotheliomatosis (RAE). This case highlights the benign course of this condition and suggests that this entity might be an intravascular histiocytosis.     

Differential activation of the endogenous leukotriene biosynthesis by two different preparations of granulocyte-macrophage colony-stimulating factor in healthy volunteers

Results from in vitro investigations and recent data obtained in patients with drug-induced cytopenia or myelodysplasia suggest that leukotrienes may be involved in mediating some of the actions of granulocyte-macrophage colony-stimulating factor (GM-CSF). In the present study, the possible role of leukotrienes was further characterized in 21 healthy individuals to avoid modification of response to GM-CSF by disease-specific variables. The effects of two different preparations of human recombinant GM-CSF, ie, glycosylated GM- CSF as expressed in a Chinese hamster ovary carcinoma (CHO) cell line and nonglycosylated GM-CSF obtained from Escherichia coli, were compared. GM-CSF was administered subcutaneously at a single dose of 0.7 nmol/kg body weight. Pharmacokinetic parameters and hematopoietic and adverse effects were monitored by blood analyses or physical examination, respectively. Leukotriene generation in vivo was evaluated by determination of leukotriene E4 and N-acetyl-leukotriene E4 in urine. After the injection of GM-CSF from E coli, serum concentrations increased and decreased more rapidly and reached a 2.3-fold higher maximum compared with GM-CSF from CHO. GM-CSF induced a biphasic change in leukocyte counts that proceeded considerably faster after the E coli preparation than after GM-CSF from CHO. The urinary leukotriene concentration increased 1.3- to 14-fold or 2.1- to 44-fold after the administration of GM-CSF from CHO or E coli, respectively. Urinary leukotriene concentrations correlated significantly with the maximum of basophil counts and correlated with the occurrence of some adverse reactions, ie, flu-like symptoms, bone pain, or dyspnoea. Our data confirm the conception that leukotrienes may play a significant role in GM-CSF action in vivo. They especially direct attention to the possible relevance of leukotrienes to untoward effects of GM-CSF treatment.