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1.
Purpose
Chest wall pain is an uncommon but bothersome late complication following lung stereotactic body radiation therapy. Despite numerous studies investigating predictors of chest wall pain, no clear consensus has been established for a chest wall constraint. The aim of our study was to investigate factors related to chest wall pain in a homogeneous group of patients treated at our institution.Patients and methods
All 122 patients were treated with the same stereotactic body radiation therapy regimen of 48 Gy in three fractions, seen for at least 6 months of follow-up, and planned with heterogeneity correction. Chest wall pain was scored according to the Common Terminology Criteria for Adverse Events classification v3.0. Patient (age, sex, diabetes, osteoporosis), tumour (planning target volume, volume of the overlapping region between planning target volume and chest wall) and chest wall dosimetric parameters (volumes receiving at least 30, 40, and 50 Gy, the minimal doses received by the highest irradiated 1, 2, and 5 cm3, and maximum dose) were collected. The correlation between chest wall pain (grade 2 or higher) and the different parameters was evaluated using univariate and multivariate logistic regression.Results
Median follow-up was 18 months (range: 6–56 months). Twelve patients out of 122 developed chest wall pain of any grade (seven with grade 1, three with grade 2 and two with grade 3 pain). In univariate analysis, only the volume receiving 30 Gy or more (P = 0.034) and the volume of the overlapping region between the planning target volume and chest wall (P = 0.038) significantly predicted chest wall pain, but these variables were later proved non-significant in multivariate regression.Conclusion
Our analysis could not find any correlation between the studied parameters and chest wall pain. Considering our present study and the wide range of differing results from the literature, a reasonable conclusion is that a constraint for chest wall pain is yet to be defined. 相似文献2.
In vitro to in vivo extrapolation (IVIVE) for next-generation risk assessment (NGRA) of chemicals requires computational modeling and faces unique challenges. Using mitochondria-related toxicity data of troglitazone (TGZ), a prototype drug known for liver toxicity, from HepaRG, HepG2, HC-04, and primary human hepatocytes, we explored inherent uncertainties in IVIVE, including cell models, cellular response endpoints, and dose metrics. A human population physiologically-based pharmacokinetic (PBPK) model for TGZ was developed to predict in vivo doses from in vitro point-of-departure (POD) concentrations. Compared to the 200–800 mg/d dose range of TGZ where liver injury was observed clinically, the predicted POD doses for the mean and top one percentile of the PBPK population were 28–372 and 15–178 mg/d respectively based on Cmax dosimetry, and 185–2552 and 83–1010 mg/d respectively based on AUC. In conclusion, although with many uncertainties, integrating in vitro assays and PBPK modeling is promising in informing liver toxicity-inducing TGZ doses. 相似文献
3.
Keyang Qian Hanqing Qian Juan Cai Wuheng Yue Xiaoxiao Yu Baorui Liu 《Pathology, research and practice》2019,215(4):755-760
Gastric cancer, one of the most common disease, has become a major public health problem worldwide. Cisplatin (DDP) has been a widely used drug for the treatment of cancer, also usually applied in gastric cancer in clinic. However, the side effects including toxicity and drug-resistance restricted the usage of DDP in clinic, so we prepared a DDP-complexed hydrogel (DDP-Gel) and investigated its efficacy in gastric cancer. For in vivo studies, MKN45-Luc cells were injected into BLAB/C node mice subcutaneously to establish gastric cancer with orthotopically grown tumors. Mice bearing tumors were treated with normal saline, DDP and DDP-Gel. Body weight and survival condition were observed and recorded. The treatment efficacy in vivo was detected by luciferase imaging and histological evaluation was performed by H&E staining of different organs. Additionally, normal ICR mice were treated with different doses of DDP/DDP-Gel to calculate their LD50 in vivo. The results showed that DDP-Gel prolonged survival time and ameliorated body weight changes of mice bearing tumors. DDP-Gel exhibited higher efficacy to inhibit tumor growth and metastasis, compared to DDP. Besides, LD50 of DDP-Gel was 166.0?mg/kg, 13.2 folds higher than DDP. As a conclusion, DDP-Gel showed a more effective and safer function than DDP in gastric cancer, which indicating that DDP-Gel might be a novel strategy for gastric cancer therapy. 相似文献
4.
慢性肾脏病是一种以肾脏功能的损伤为主要表现,并可累及全身多脏器的慢性进展性疾病。中医辨证治疗本病在延缓病情、改善预后等方面具有显著的优势。通过中医理论研究及临床经验总结,笔者提出从“肾毒”论治慢性肾脏病,认为其不仅是本病的致病因素,更是重要的病理产物,是本病发生发展、迁延难愈的关键。在治疗上提出以“益肾元、解肾毒”为大法,并根据不同兼夹辨证施治,采用药对,长治缓图。以“肾毒”立论拟定的经验方苏茵解毒方,在临床治疗和实验研究上均显示出明显的效果,并已制备成院内制剂临床使用,在疗效及经济效益方面均具有显著的优势。 相似文献
5.
6.
抗生素的定义,首先来自于20世纪40年代链霉素的发现。在随后的几十年中,其他氨基糖苷类抗生素家族被大量发现并广泛应用,一度成为抗革兰阴性菌感染的首选抗生素。但由于其毒副作用较大,并且细菌对其不断产生耐药性,加上其他结构类别的新型抗生素的不断发现,使其一度几乎退出历史舞台。然而随着多重耐药细菌引起的感染率急剧上升,人们开始关注氨基糖苷类抗生素作为几种重要的治疗革兰阴性病原体的方案之一,并且发掘了其在治疗感染性疾病、艾滋病和遗传性疾病的潜力,使这个“老牌”抗生素重焕生机。 相似文献
7.
8.
Meg Sears C Robin Walker Richard HC van der Jagt Paul Claman 《Paediatrics & child health》2006,11(4):229-234
Pesticide regulation is examined in the context of Health Canada’s Pest Management Regulatory Agency’s assessment of the chlorophenoxy herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) for turf. 2,4-D is the most common herbicide used to kill weeds in grass.The medical literature does not uniformly indicate harms from herbicides. However, the balance of epidemiological research suggests that 2,4-D can be persuasively linked to cancers, neurological impairment and reproductive problems. These may arise from 2,4-D itself, from breakdown products or dioxin contamination, or from a combination of chemicals.Regulators rely largely on toxicology, but experiments may not replicate exposures from 2,4-D application to lawns because environmental breakdown products (eg, 2,4-dichlorophenol) may not accumulate and selected herbicides are possibly less contaminated. Dioxins are bioaccumulative chemicals that may cause cancer, harm neurological development, impair reproduction, disrupt the endocrine system and alter immune function. No dioxin analyses were submitted to the Pest Management Regulatory Agency, and the principal contaminants of 2,4-D are not among the 17 congeners covered in pesticide regulation. Independent assessment of all dioxins is needed, in tissues and in the environment.The 2,4-D assessment does not approach standards for ethics, rigour or transparency in medical research. Canada needs a stronger regulator for pesticides. Potentially toxic chemicals should not be registered when more benign solutions exist, risks are not clearly quantifiable or potential risks outweigh benefits. Until landscaping pesticides are curtailed nationally, local bylaws and Quebec’s Pesticide Code are prudent measures to protect public health. Physicians have a role in public education regarding pesticides. 相似文献
9.
C. J. Bowden W. D. Figg N. A. Dawson O. Sartor R. J. Bitton M. S. Weinberger Donna Headlee Eddie Reed C. E. Myers M. R. Cooper 《Cancer chemotherapy and pharmacology》1996,39(1-2):1-8
Introduction: Suramin is a synthetic polysulfonated naphthylurea which has been used for the treatment of African trypanosomiasis and onchocerciasis,
but since the mid-1980s has received attention as a possible antiretroviral and antineoplastic agent. Objective: This clinical trial of suramin was undertaken as a phase I/II study in patients with hormone-refractory prostate cancer,
with the hypothesis that the intensity of therapy with suramin could be increased significantly if measures were undertaken
to maintain the plasma concentrations of the drug under 300 μg/ml. Methods: We report the clinical results of this trial, wherein patients were treated at three different targeted plasma suramin concentrations
(275, 215 and 175 μg/ml) for varying periods of time (2, 4 or 8 weeks), with delivery of the drug by continuous intravenous
infusion. Results: The major toxicity observed in this trial was neurologic, consisting of a motor and sensory peripheral neuropathy that resulted
in both paresis and paralysis of the limbs. Nearly all of this severe (CTEP grade III, IV) neurologic toxicity was observed
in the patients treated at a plasma suramin concentration of 275 μg/ml for 4 or more weeks. A single patient treated at 215 μg/ml
for 8 weeks developed moderate (CTEP grade III) proximal lower extremity weakness, and no patient treated at 175 μg/ml developed
this toxicity. The second most common toxicity observed was infection of the central venous catheter. The overall response
rate for all of the evaluable patients was 17% (13 of 75 patients). In addition, prostate-specific antigen (PSA)-defined responses
were observed in six patients receiving therapy at 175 μg/ml, but these responses were confounded by cessation of therapy
with flutamide during suramin treatment. Conclusions: In summary, although plasma suramin concentrations were maintained below 300 μg/ml, neurologic toxicity nonetheless occurred
with high frequency in patients treated at 275 μg/ml for 4 or more weeks. Therapy at 215 and 175 μg/ml was in general well
tolerated, but central venous catheter-related infection, as well as the inconvenience and expense of continuous infusional
therapy, make this method of drug delivery impractical. Only moderate antitumor activity was observed during this trial, but
it is possible that both continuation of flutamide and flutamide withdrawal during suramin therapy confounded the assessment
of suramin’s activity in hormone-refractory prostate cancer.
Received: 9 June 1995/Accepted: 18 March 1996 相似文献
10.
乙基叔丁醚对动物局部和全身的毒性研究 总被引:3,自引:0,他引:3
为了主人乙基叔丁醚(ETBE)的毒性作用,探讨它的灌注溶解治疗胆固醇结石的可能性。我们做了该药物的动物毒性实验,对比ETBE和MTBE(甲基叔丁醚)对动物的局部组织和全身毒性作用。局部毒性实验是对大白兔胆囊进行灌注后,病理观察组织变化。全身毒性实验是通过对小鼠腹腔注射药物的半致死量作对比。结果发现,ETBE对兔的胆囊、胆部属这和十二指肠的损害较MTBE组动物轻。ETBE摇篮腔注射半致死量LD50) 相似文献