钴60放射法制备免疫功能抑制大鼠模型

目的通过系统的钴60放射计划,对大鼠免疫功能抑制的合适剂量进行评估,为干细胞移植研究提供合适的的动物模型。方法SD大鼠随机分为12.5Gy、10Gy、7.5Gy、5Gy4个剂量组,10只/组。计算放射后2个月的死亡率。检测白细胞数量,评价各剂量组动物的白细胞参考值范围。结合死亡率和白细胞参考值范围,确定合适的放射剂量。通过对外周血中性粒细胞(PMN)吞噬实验和外周血白细胞移行抑制实验(MIT),对细胞免疫功能进行检测。结果行12.5Gy照射的大鼠,3d内全部死亡;10Gy放射后的大鼠在1个月内全部死亡;7.5Gy照射的大鼠2个月内死亡1只;5Gy照射的大鼠没有死亡情况发生。设定95%作为可信区间,计算白细胞数量参考值范围(109个/L),未放疗组:16.978+1.96×6.46;5Gy放疗组:4.93+1.96×0.72;7.5Gy放疗组:2.313+1.96×0.782;10Gy放疗组:1.03+1.96×0.507。t检验表明,随着放疗剂量的增加,各实验组的白细胞数量显著减少。对于细胞免疫功能的检测,外周血中性粒细胞(PMN)吞噬实验结果表明,机体全身免疫功能降低;外周血白细胞移行抑制实验(MIT)表明,机体T细胞免疫功能降低。结论7.5Gy可以一定程度上抑制大鼠的免疫功能,为合适的放疗剂量。     

Upregulation of VEGF and FGF2 in normal rat brain after experimental intraoperative radiation therapy

The expression of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF)2 in the irradiated brain was examined to test how a single high dose radiation, similar to that used for intraoperative radiation therapy given to the normal cerebrum, can affect the vascular endothelium. After a burr hole trephination in the rat skull, the cerebral hemisphere was exposed to a single 10 Gy dose of gamma rays, and the radiation effect was assessed at 1, 2, 4, 6, and 8 weeks after irradiation. Histological changes, such as reactive gliosis, inflammation, vascular proliferation and necrosis, were correlated with the duration after irradiation. Significant VEGF and FGF2 expression in the 2- and 8-week were detected by enzyme-linked immunosorbent assay quantification in the radiation group. Immunohistochemical study for VEGF was done and the number of positive cells gradually increased over time, compared with the sham operation group. In conclusion, the radiation injuries consisted of radiation necrosis associated with the expression of VEGF and FGF2. These findings indicate that VEGF and FGF2 may play a role in the radiation injuries after intraoperative single high-dose irradiation.     

Einsparung von Diclofenac durch B-Vitamine: Ergebnisse einer randomisierten Doppelblindprüfung mit reduzierten Tagesdosierungen von Diclofenac (75 mg Diclofenac versus 75 mg Diclofenac plus B-Vitamine) bei akuten Lendenwirbelsäulensyndromen

Summary Pain syndromes of the lumbar spine are one of the main problems in orthopedic practice. The therapeutic effect of NSAIDs is not subject to doubt in this connection.But considering that the application of NSAIDs is frequently associated with side effects, a reduction of dosage would be to the patient's benefit. Clinical studies have shown that concomitant treatment with vitamins B₁, B₆, B₁₂ and diclofenac leads to a more efficient pain relief than treatment using diclofenac alone and thus provides the possibility of saving NSAIDs.This clinical trial was carried out in order to determine whether these results can also be achieved when a reduced dosage of diclofenac (75 mg daily) is used.123 patients with acute pain syndromes of the lumbar spine were treated with either B-vitamins and diclofenac or diclofenac alone for a maximum of 7 days. There was the option to terminate therapy in the trial after 3–4 days in the case of total pain relief.45 patients could stop the treatment due to remission of symptoms. 30 patients belonged to the combination therapy group, the other 15 took diclofenac alone; this difference is statistically significant (p< 0.05).All parameters concerning pain relief and movement of the vertebral column showed statistically significant differences in favour of the B-vitamin-diclofenac-combination, too.The results document the positive influence of B-vitamins on painful vertebral syndromes and indicate that B-vitamins contribute to saving of NSAIDs by shortening the treatment time and reducing daily NSAID-dosage.

     

A polyexponential deconvolution method. Evaluation of the “gastrointestinal bioavailability” and meanin vivo dissolution time of some ibuprofen dosage forms

A new deconvolution algorithm (DCON) suitable for pharmacokinetic applications is presented. It requires that both the impulse and input responses, typically systemic drug levels, be well described by polyexponential equations. DCON has a wider range of applications than an earlier method (DECONV) from which it is derived. A FORTRAN program is provided, making implementation of the technique a simple matter. DCON is demonstrated to evaluate the GI bioavailability, defined as the rate and the extent of gastrointestinal drug release, of various ibuprofen dosage forms. The GI drug release kinetics exemplifies a pharmacokinetic system which cannot be evaluated using the previous deconvolution algorithm (DECONV) because of an initial zero drug level response. This limitation is not found in DCON. It is also demonstrated how the mean in vivo dissolution time MDT can be evaluated by deconvolution.     

Radiotherapy alone in breast cancer. I. Analysis of tumor parameters, tumor dose and local control: the experience of the Gustave-Roussy Institute and the Princess Margaret Hospital

This retrospective study involved 463 breast cancer patients treated by radiotherapy alone at the Princess Margaret Hospital and at the Institut Gustave-Roussy. These patients either had operable tumors, but were unfit for general anesthesia, or had inoperable tumors due to local contraindications to surgery. Results were analyzed according to tumor response, local recurrence rate, tumor size, tumor fixation, nodal fixation and tumor dose. Conventional statistical analysis of local control showed two significant factors: tumor dose and tumor size. Multivariate analysis permitted to define an "individual risk" (IR) of local recurrence according to three independent factors: tumor size, tumor fixation, and nodal fixation. It was shown that the IR was a good prognostic factor for local control. Increase in tumor dose gave a similar effect in the local recurrence relative risk for all the IR groups. According to the slope of the dose-effect curve, it was deduced that a dose increase of 15 Gy can decrease the relative risk of local recurrence 2-fold. In fact, it was shown that tumor dose was the most significant independent factor on local control, able to produce up to a 10-fold increase compared to 2-fold decrease for tumor size. If the IR of local recurrence is known, a theoretical predictive value on local control, taking into account the tumor dose, can be determined according to the present data.     

Malignant obstructive jaundice: treatment with external-beam and intracavitary radiotherapy

Eleven patients with obstructive jaundice from unresectable cholangiocarcinoma, metastatic porta hepatis adenopathy, or direct compression from a pancreatic malignancy were treated at the Stanford University Medical Center from 1978-1983 with an external drainage procedure followed by high-dose external-beam radiotherapy and by an intracavitary boost to the site of obstruction with Iridium192 (Ir192). A median dose of 5000 cGy was delivered with 4-6 Mv photons to the tumor bed and regional lymphatics in 9 patients, 1 patient received 2100 cGy to the liver in accelerated fractions because of extensive intrahepatic disease, and 1 patient received 7000 "equivalent" cGy to his pancreatic tumor bed and regional lymphatics with neon heavy particles. An Ir192 wire source later delivered a 3100-10,647 cGy boost to the site of biliary obstruction in each patient, for a mean combined dose of 10,202 cGy to a point 5 mm from the line source. Few acute complications were noted, but 3/11 patients (27%) subsequently developed upper gastrointestinal bleeding from duodenitis or frank duodenal ulceration 4 weeks, 4 months, and 7.5 months following treatment. Eight patients died--5 with local recurrence +/- distant metastasis, 2 with sepsis, and 1 with widespread systemic metastasis. Autopsies revealed no evidence of biliary tree obstruction in 3/3 patients. Mean survival time from initial laparotomy and bypass was 16.1 months, and from radiotherapy completion was 8.3 months. Evolution of radiation treatment techniques for biliary obstruction in the literature is reviewed. High-dose external-beam therapy followed by high-dose Ir192 intracavitary boost is well tolerated and provides significant palliation. Survival of these aggressively managed patients approaches that of patients with primarily resectable tumors.     

Serum digoxin concentrations in a representative digoxin — Consuming adult population

Summary As part of health examination of a representative sample of an adult population (n=8000) serum digoxin concentration was measured in 661 patients on continuous digoxin therapy. The prescribed mean daily dose of digoxin was significantly higher in men (223 µg) than in women (201 µg); the dose significantly decreased with increasing age. The mean serum digoxin concentration was the same in men and women and it differed insignificantly between age groups, although older persons tended to have a higher concentration. The age — adjusted mean steady state digoxin concentration was 1.02 ng/ml in men and 0.98 ng/ml in women; in about 60% the concentration was within the therapeutic range (0.80–2.00 ng/ml). The concentrations were clearly related to daily dose of digoxin. At equal dose levels old persons tended to have higher concentrations than younger persons. The interindividual variation in serum digoxin concentrations was very wide. However, when digoxin measurements in the same subjects were repeated about three months later, a good correlation between the two measurements was found. The interval between the last dose of digoxin and the collection of blood (up to 41 h) had relatively little effect on individual serum digoxin concentrations. Patients on concomitant thiazide or loop diuretic therapy had the same mean serum digoxin concentration as those not-receiving a diuretic. The mean concentration was significantly higher in patients taking a thiazide or loop diuretic combined with triamterene. The difference may have been due to an interaction between triamterene and digoxin.     

放射治疗对乳腺癌患者外周血免疫系统相关指标的影响

目的:研究分析放射治疗对乳腺癌患者免疫系统相关指标的影响。方法:选取在医院就诊的6例病理诊断为乳腺癌Ⅱ~Ⅲ期患者,将所有患者放射治疗前(0 Gy)静脉血样本定义为对照组、放射治疗20 Gy和50 Gy照射后静脉血样本分别定义为20 Gy组和50 Gy组,于放射治疗10次后、25次后采集不同放射治疗累积剂量24 h后静脉血8 ml;采用流式细胞术检测所有受检者不同剂量放射治疗后外周血淋巴细胞亚群百分数、外周血淋巴细胞凋亡及细胞周期的改变;实时荧光定量聚合酶链反应(q RT-PCR)法检测外周血淋巴细胞微小核糖核酸(miRNA)的改变。结果:乳腺癌患者20 Gy组和50 Gy组照射后与对照组比较,淋巴细胞亚群CD3⁺、CD4⁺/CD8-和CD4⁺/CD8⁺表达水平均呈下调趋势,CD4^-/CD8⁺呈上升趋势,但差异均无统计学意义;20 Gy组T细胞抗原受体(TCR)/CD3明显下调,与对照组比较差异有统计学意义(Z=-2.008,P<0.05),50 Gy组TCR/CD3有所回升,但差异无统计学意义。不同剂量的两组照射后乳腺癌患者mi RNA-150、mi RNA-210表达水平随剂量增加呈降低趋势,50 Gy组表达水平明显降低,与对照组相比差异有统计学意义(Z=-2.242,Z=-2.402;P<0.05)。结论:放射治疗未引起乳腺癌患者明显的免疫功能抑制,可能是通过改变mi RNA-150、mi RNA-210的通路而抑制肿瘤的生长。     

视神经萎缩的治疗临床研究

目的 探讨视神经萎缩的有效治疗方法。方法 对324例526例眼视神经萎缩患,用胞二磷胆碱、肌苷做球后注射。结果 临床治愈88例,显效261例,进步106眼,有效率86．9％,收到了较满意的效果。结论 胞二磷胆碱、肌苷可通过卵磷脂的合成改善视神经周围的血液循环,刺激和促进视神经纤维的生物修补,从而导致视神经功能的改善和恢复。