御生堂减肥胶囊的急性毒性及致突变性

背景与目的:测试御生堂减肥胶囊的急性毒性及致突变性.材料与方法:按<食品安全性毒理学评价程序和方法>进行了小鼠的急性毒性试验、小鼠骨髓细胞微核试验、小鼠精子畸形试验、大鼠30 d喂养试验及Ames试验.结果:小鼠LD50＞215 000mg/kg,小鼠骨髓细胞微核试验和小鼠精子畸形试验测试组和对照组相比差异均无显著性,Ames试验中不同剂量组在加S9和不加S9条件下的回变菌落数均未超过空白对照组回变菌落数的2倍;大鼠30 d喂养试验各剂量组动物生长发育良好,血液及生化指标均在正常范围内,各试验组与对照组比较差异无显著性,病理学检查结果肝、肾、胃、肠均正常.结论:御生堂减肥胶囊属无毒物质,致突变试验及30 d喂养试验均为阴性结果.     

肾癌组织 DGFR及c-Fos的表达研究

目的探讨PDGFR及蛋白c-Fos的表达与肾细胞癌(CC)发生的关系.方法应用免疫组化SP法检测12例正常肾组织、14例癌旁肾组织、46例肾细胞癌组织中PDGFR和c-Fos蛋白的表达,并结合肾癌的分级、分期和随访结果进行分析.结果 PDGFR及c-Fos在RCC组织中的表达阳性率分别为73.91%及52.17%,明显高于正常组织及癌旁组织,有显著性差异.PDGFR在透明细胞癌中的表达阳性率明显高于颗粒细胞癌,有显著性差异.PDGFR及c-Fos在RCC组织血管中的表达明显增强.PDGFR的表达与RCC的分级相关.结论 PDGFR及c-Fos的过度表达与RCC的发生密切相关,并与肿瘤血管形成相关.PDGFR的表达与RCC的恶性程度相关.     

肾恶性横纹肌样瘤临床病理分析及超微结构观察

目的:探讨肾恶性横纹肌样瘤(MRTK)的临床病理表现及超微结构特点。方法:用光镜、免疫组化及电镜等方法观察其病理组织学特点、免疫组化表达及超微结构。结果:光镜的典型特点是肿瘤细胞弥漫性排列,呈圆形、椭圆形及不规则形,胞质丰富,嗜酸性,部分胞质内可见透明状小体,细胞核圆形或椭圆形,核膜厚,核仁清楚,有的细胞核呈空泡状。部分核偏向一侧似浆细胞样。细胞内外见红染的包涵体。免疫组化显示肿瘤可表达多种抗原。电镜观察特异性表现是胞质内见中间丝及圆形不规则形纤维状或轮状小体。结论:肿瘤细胞弥漫排列呈浆细胞样,免疫组化多方向表达,可向神经性、上皮性、肌性等方向分化。电镜下胞质内中间丝及纤维轮状小体是特异性诊断标志。     

Serious adverse effects of amifostine during radiotherapy in head and neck cancer patients

Background and purpose: Amifostine has been shown to protect against xerostomia induced by radiotherapy for head and neck cancer, but its impact on the therapeutic index is unknown. This is the first report focusing on amifostine related adverse effects leading to discontinuation of amifostine treatment.

Patients and methods: Thirty-nine patients from two centers irradiated for head and neck cancer received i.v.-infusions of amifostine prior to each radiation fraction. In a phase III study, two daily amifostine doses, 200 mg/m² (n=21) and 340 mg/m² (n=18), were compared for protection against radiation induced toxicity. Total radiation dose was 60–70 Gy (2 Gy per fraction), nine patients received concurrent chemotherapy with cisplatin/5-FU. amifostine was usually discontinued after >1 episode of serious toxicity during subsequent treatment sessions.

Results: In 16/39 patients (41%) amifostine was discontinued due to severe adverse effects, which led to discontinuation of the phase III study. In four of 16 patients radiotherapy was delayed due to amifostine related adverse effects for 1–3 days. Discontinuation occurred more often in patients receiving chemotherapy. The results led to a literature review for amifostine treatment during radiotherapy in head and neck cancer patients. Regarding our series and published series using an amifostine schedule comparable to ours, total discontinuation rate was 27% (57/214). Discontinuation was significantly influenced by chemotherapy (P=0.007), but not by amifostine dose (P=0.156).

Conclusion: Daily i.v. administration of amifostine during radiotherapy in head and neck cancer is associated with a high rate of serious adverse effects leading to discontinuation of amifostine treatment and sometimes delay of radiotherapy.     

Intra-arterial administration of carboplatin and the blood brain barrier permeabilizing agent,RMP-7: A toxicologic evaluation in swine

RMP-7 is a bradykinin B2 receptor agonist shown to permeabilize the blood-brain barrier, especially that associated with brain tumors, when administered via both intracarotid and intravenous routes. Both routes of administration are currently being tested in human trials in combination with the chemotherapeutic agent carboplatin as therapy for gliomas. As an essential prerequisite to the initial intracarotid clinical trials, the potential neurotoxicity of intra-arterial administration of RMP-7 (at a high or low dose), alone and in combination with carboplatin, was assessed in anesthetized Red Duroc swine. Five treatment groups were evaluated with each pig receiving a series of alternating, intra-arterial infusions of RMP-7 (or saline) followed by carboplatin (or saline), as follows: (1) vehicle control: saline/saline; (2) carboplatin only control: saline/carboplatin (50 mg total); (3) RMP-7 only control: RMP-7 (750 ng/kg)/saline; (4) low dose combination: RMP-7 (75 ng/kg)/carboplatin (50 mg total); and (5) high dose combination: RMP-7 (750 ng/kg)/carboplatin (50 mg total). For each subject, one of the alternating dosing sequences (above) was repeated four times during a single dosing session which lasted approximately 40 minutes. Assessments during the in-life phase of the study in the pre- and post-treatment periods consisted of heart rate, arterial blood pressure (systolic, diastolic, and mean), blood gases, body weight, general clinical observations (including evaluation for neurological deficit) and clinical pathology (including a comprehensive battery of standard blood coagulation, hematological and serum chemistry tests). In addition, during the time of treatment, heart rate and arterial blood pressure were monitored. The animals were terminated two weeks after dosing and the brain and rete mirabile (distal to site of infusion) were evaluated for gross and histopathological abnormalities. The histopathology analysis included a reader-blinded analysis using low and high power light microscopic examination of both H&E and Kluver-Berrera stained sections through several key cortical and subcortical brain regions. Transient decreases in arterial blood pressure (mean of 10–25 mmHg) were observed in both groups receiving the high dose of RMP-7 (i.e., 750 ng/kg). No other side effects attributable to RMP-7 and/or carboplatin were observed, and clinical observations revealed no evidence of neurologic deficits. Post-mortem examination revealed no evidence of CNS or cerebral vascular pathology attributable to carboplatin and RMP-7. This study demonstrates that intracarotid administration of the maximum tolerated dose of RMP-7 (750 ng/kg) alone, or in combination with carboplatin (50 mg) is not accompanied by any serious adverse effect, apparent cerebrovascular abnormality or neuropathologic consequence and offers further evidence for the safety of this novel therapeutic approach for enhancing delivery of chemotherapeutics to brain tumors.     

Clinical phase I study with one-hour paclitaxel infusion

Background: Paclitaxel (PAC) is one of the major anti-cancer drugs,effective in different tumors. Studies with 24-hour infusion with 135mg/m² and a three-hour infusion with 175 mg/m²showed a significant schedule-dependent toxicity. We evaluated a one-hourinfusion schedule within a phase I study to determine the dose limitingtoxicity (DLT), the maximum tolerated dose (MTD), and the anti-cancerefficacy.Patients and methods: Patients with advanced malignant tumors weretreated within cohorts by one-hour infusional paclitaxel starting with 150mg/m² and stepwise escalation with 25 mg/m²increments. Therapy was repeated in three-week intervals. Cycles wererepeated until progression. Toxicity was closely monitored, anti-cancerefficacy was only evaluated in those patients who received at minimum twotreatment cycles.Results: Thirty-four patients entered the study (11 NSCLC, five SCLC,seven ovarian cancer, one cervix cancer, nine MBC, one HN cancer). The MTDwas PAC 250 mg/m². The DLT was central and peripheralneuropathy (WHO grade 3). Other significant toxicities were fatigue,myalgia/arthralgia and paraesthesia. No significant myelotoxicity wasobserved. Totally twentyone patients were evaluable for response. A partialresponse was observed in five (24%) patients (two NSCLC, two ovariancancer, one head and neck cancer). Three (14%) patients had stabledisease and in 13 (62%) patients progressive disease was observed.Conclusions: Paclitaxel 225 mg/m² on day 1 administered asone-hour infusion and repeated every three weeks can be given safely, featuredno relevant myelotoxicity, and is the recommended dose for phase II studies.     

Teniposide or carboplatin in patients with recurrent or advanced cervical carcinoma: A randomized phase II trial

Thomsen TK, Pfeiffer P, Bertelsen K. Teniposide or carboplatin in patients with recurrent or advanced cervical carcinoma: A randomized phase II trial. Int J Gynecol Cancer 1998; 8 : 310–314.
The aim of the present study was to investigate response rates, time to progression, and survival with teniposide or carboplatin in patients with advanced or recurrent cervical cancer and to estimate the toxicity of each drug regimen.
Twenty-eight patients with recurrent or advanced cervical cancer entered the study. Two patients were ineligible (severe renal impairment, n = 1; performance status 3, n = 1) and were excluded from the analysis. The remaining 26 patients were randomized to either carboplatin (400 mg/m² on day 1, intravenously every four weeks) or teniposide (125 mg/m² on days 1, 2 and 3, intravenously every four weeks). Twelve patients were randomized to the carboplatin arm and 14 patients to the teniposide arm. They were all comparable with respect to age, performance status, histology, primary FIGO stage, and prior therapy.
Response was seen in four patients in each group (33% and 29%, respectively), all but one being partial. (One patient in the teniposide group had complete response). Time to progression and median survival were similar in the two groups (median time to progression 20/17 weeks and median survival 40/41 weeks, respectively.)
In general, toxicity was moderate. Leukopenia (WHO grade 3 or 4) was seen in one patient treated with teniposide, and thrombocytopenia (WHO grade 3 or 4) in one patient treated with carboplatin. Eleven patients (79%) in the teniposide group had alopecia requiring a wig. The study implies that both drugs have some activity in cervical cancer. Carboplatin has the advantage that it can be administered on an out-patient basis.     

马根维显动态增强核磁共振评价肾积水疗效

目的了解马根维显(Gd-DTPA)动态增强核磁共振(MRI)评估肾积水术后疗效的应用价值。方法单侧肾积水患者11例,年龄7～42岁,平均19.5岁,均为男性;左侧肾积水9例,右侧2例;病因经静脉尿路造影(intravenousurography,IVU)和B超确诊,10例为先天性肾盂输尿管连接部狭窄(pelvicureterjunctionobstruction,PUJO),1例为输尿管中段慢性炎症所致不完全性梗阻;10例PUJO实施狭窄部成形术,另1例施行输尿管狭窄段切除并输尿管端端吻合术。应用Gd-DTPA作为对比剂,分别在术前1个月和术后3个月实施动态增强MRI检查,选取肾实质、肾盂和集合系统的类圆形区域作为兴趣区(regionofinteresting,ROI),计算不同时间点不同兴趣区的信号强度(signalintensity,SI)和相对信号强度(relativeSI,RSI),绘制T-SI曲线,对术前术后肾脏的形态和功能状态进行评估和比较。结果积水肾脏术前肾实质与术后综合评价无显著性差异(P>0.05),肾盂和集合系统排泄对比剂明显减慢,各ROI和SI以及持续时间与术后肾脏相比均有明显的差异(P<0.05)。结论动态增强MRI作为一种简单、安全无创的技术、联合评估肾形态和功能,对于评价肾积水手术疗效具有重要的临床价值。     

Frequency of pancreatitis after endoscopic retrograde cholangiopancreatography with iopromid or iotrolan: a randomized trial

Blood isotone contrast media is considered to be less toxic to vascular and pancreatic duct endothelium than high-osmolar contrast media. In this study we assessed the impact of a low-osmolar contrast agent compared with a blood isotone product on pancreatic damage induced by endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic retrograde sphincterotomy (EST). In a prospective trial 42 consecutive ERCP/EST patients were randomized to receive either iopromid, a low-osmolar non-ionic contrast agent (770 mosmol/kg H₂O), or iotrolan, a blood-isotone non-ionic product (320 mosmol/kg H₂O). The endoscopies were performed by two experienced endoscopists. Forty patients were included in the study. Blood samples were collected before and 40 min, 2, 4, 6 and 24 h after the endoscopic procedure. Samples were analysed for pancreatic serum enzymes, acute-phase proteins and blood counts. A clinical pain score was investigated. Post-ERCP pancreatitis was diagnosed in 2 patients in the iopromid group and in 5 patients in the iotrolan group. There was no significant difference between groups in the time course of pancreatic serum enzymes, acute-phase proteins or in the pain score. Due to the small number of patients in this study, only stronger differences caused by the two contrast media could have led to statistically significant results. We did not observe statistically significant differences in comparing iotrolan and iopromid concerning ERCP/EST-induced pancreatic damage. Received: 26 February 1999; Revised: 14 May 1999; Accepted: 9 June 1999     

Detection and characterisation of renal lesions by multiphasic helical CT

Purpose: The fast helical CT technique allows examination of the kidneys during different phases of contrast medium enhancement. However, every additional phase increases the radiation dosage to the patients. We investigated the detection rate and characterisation of renal lesions during different phases and evaluated them separately, and considered the possibility of excluding phases without loss of important information.Material and Methods: Sixty patients who underwent contrast-enhanced multiphasic renal helical CT examination were included. Every CT phase was evaluated separately. The number of lesions and the characteristics of the lesions were noted and all lesions were viewed together.Results: A total of 153 cysts and 17 solid lesions were detected. The largest and an equal number of cysts (142/143) was detected in the nephrographic and excretory phases. However, the nephrographic phase detected more cortical cysts and the excretory phase detected more sinus cysts. All solid lesions were detected in all phases. Renal parenchymal tumours were best characterised in the cortical phase and angiomyolipomas in the native phase.Conclusion: The cortical phase was best for characterisation of renal parenchymal tumours. The nephrographic and excretory phases were best in detecting and characterising renal cysts. The nephrographic phase was the phase giving the least diagnostic information.