吗啡和曲马多对MADB-106乳腺癌细胞增殖和凋亡的影响

目的观察不同浓度吗啡和曲马多对MADB-106乳腺癌细胞增殖和凋亡的影响,并对其机制进行初步研究。方法将不同浓度吗啡和曲马多与MADB-106乳腺癌细胞直接作用24 h后采用流式细胞法检测细胞凋亡,MTT法检测细胞增殖。采用Western blot法检测细胞半胱氨酸蛋白酶-3（caspase-3）和半胱氨酸蛋白酶-8（caspase-8）的表达。结果吗啡和曲马多均可浓度依赖性促进MADB-106乳腺癌细胞的凋亡、抑制细胞生长与增殖;等效镇痛浓度吗啡与曲马多对MADB-106乳腺癌细胞的增殖与凋亡的影响并无差异;吗啡可促进MADB-106乳腺癌细胞caspase-3和caspase-8激活片段表达。而曲马多仅促进caspase-3激活片段表达,caspase-8激活片段无显著变化。结论吗啡和曲马多均可浓度依赖性促进MADB-106乳腺癌细胞的凋亡、抑制肿瘤细胞的生长与增殖;吗啡和曲马多均可激活caspase-3途径诱导MADB-106乳腺癌细胞的凋亡,同时吗啡可激活caspase-8途径,而曲马多无此作用。     

2009-2012年某军区放射工作人员个人剂量监测结果分析

目的：了解近年来某军区放射工作人员的个人外照射剂量水平和分布,查找薄弱环节,提高防护水平。方法采用热释光方法,对2009-2012年某军区放射工作人员的个人剂量进行监测,并对结果进行统计和分析。结果4年人均年剂量为0．59 mSv,与往年相比有很大降低;不同工种的剂量分布从高到低依次为介入治疗、核医学、放射治疗和放射诊断;介入治疗是集体年剂量的主要贡献者,虽然其人均年剂量有下降趋势,但年剂量超过5 mSv的人数随监测人数的增加而逐年增加。结论某军区大部分放射工作人员的个人剂量水平较低,但仍有部分放射工作者剂量偏高,还需加大监督力度,增强防护意识,改善防护条件。     

药品生产企业建立药品不良反应报告和监测管理制度的现状及思考

我国的《药品不良反应报告和监测管理办法》强制要求药品生产企业内部建立药品不良反应报告和监测管理制度。通过分析企业建立报告制度的现状,借鉴欧盟的相关政策要求,探讨改进我国企业落实该报告制度的方法及政府监管方式。     

Can lower risk patients presenting with transient ischaemic attack be safely managed as outpatients?

This study aimed to examine outcome in low risk transient ischaemic attack (TIA) patients presenting to emergency departments (ED) in a regional Australian setting discharged on antiplatelet therapy with expedited neurology review. All patients presenting to Gosford or Wyong Hospital ED with TIA, for whom faxed referrals to the neurology department were received between October 2008 and July 2010, were included in this prospective cohort study. Classification of low risk was based on an age, blood pressure, clinical features, duration of symptoms and diabetes (ABCD²) score <4 and the absence of high risk features, including known carotid disease, crescendo TIA, or atrial fibrillation. Patients with ABCD² scores ⩾4 or with high risk features were discussed with the neurologist on call (a decision regarding discharge or admission was then made at the neurologist’s discretion). Patients were investigated with a brain CT scan and/or CT angiography, routine pathology, and an electrocardiogram. All discharged patients were commenced on antiplatelet therapy and asked to follow up with their local medical officer within 7 days. The patients were contacted by the neurology department to arrange follow-up. Our primary outcome was the number of subsequent strokes occurring within 90 days. Of 200 discharged patients for whom referrals were received, three patients had a stroke within 90 days. None of these would have been prevented through hospitalisation. In conclusion, medical assessment, expedited investigation with immediate commencement of secondary prevention and outpatient neurology review may be a reasonable alternative to admission for low risk patients presenting to the ED with TIA.     

Cushing’s disease: A single centre’s experience using the linear accelerator (LINAC) for stereotactic radiosurgery and fractionated stereotactic radiotherapy

Cushing’s disease is hypercortisolaemia secondary to an adrenocorticotrophic hormone secreting pituitary adenoma. Primary management is almost always surgical, with limited effective medical interventions available. Adjuvant therapy in the form of radiation is gaining popularity, with the bulk of the literature related to the Gamma Knife. We present the results from our own institution using the linear accelerator (LINAC) since 1990. Thirty-six patients who underwent stereotactic radiosurgery (SRS), one patient who underwent fractionated stereotactic radiotherapy (FSRT) and for the purposes of comparison, 13 patients who had undergone conventional radiotherapy prior to 1990, were included in the analysis. Serum cortisol levels improved in nine of 36 (25%) SRS patients and 24 hour urinary free cortisol levels improved in 13 of 36 patients (36.1%). Tumour volume control was excellent in the SRS group with deterioration in only one patient (3%). The patient who underwent FSRT had a highly aggressive tumour refractory to radiation.     

Cerebral arteriostenosis associated with elevated serum-immunoglobulin E level in young adults without risk factors for ischemic stroke: A possible manifestation of cerebral vasculitis?

We report a series of young adults with symptomatic cerebral arteriostenosis characterized by elevated serum immunoglobulin (Ig) E levels. All patients had no definite risk factors for cerebral vascular diseases. The clinical data of 26 young adults (age 18–50 years) with ischemic stroke, characterized only by increased serum IgE levels and without risk factors for cerebral vascular disease, were retrospectively reviewed. Arteriostenosis was surveyed and followed-up by digital subtraction angiography (DSA), and the stenosis rate was estimated using the warfarin–aspirin symptomatic intracranial disease technique. All patients were treated with corticosteroids according to the common strategy for vasculitis. There was no recurrent stroke during follow-up. The mean degree of stenosis before and after treatment was 69.3 ± 29.8% and 47.9 ± 45.1%, respectively. The difference of stenosis rates between initial and follow-up DSA evaluation was significant using a paired samples test (21.31 ± 26.88, 95% confidence interval [CI] 13.58–29.03, t = 5.55, p < 0.001). Kaplan–Meier survival analysis revealed that the 13-month cumulative improved lesion rate was 40.3 ± 8.7%. This remained the same at 18 months. The mean time to lesion improvement was 12.58 ± 0.96 months (95% CI 10.70–14.46) and median time was 13 ± 3.88 months (95% CI 5.39–20.61). To our knowledge, cerebral arteriostenosis with only elevated IgE serum levels has not been reported. Our data showed that corticosteroid treatment can achieve clinical and artery improvement. This suggests that the cerebral arteriostenosis seen in our study might be caused by some specific type of vessel inflammation.     

Early response to chemotherapy as an indicator for the management of germinoma-like tumors of the pineal and/or suprasellar regions

Recent advances in diagnostic imaging and experience with germinomas may allow for the differentiation of central nervous system germinomas from other tumors based on clinical information, without histological verification. We retrospectively analyzed clinically diagnosed germinoma-like tumors of the pineal and/or suprasellar regions. This was done to evaluate the efficacy of our strategy of defining germinoma-compatible tumors based on good responses to initial chemotherapy. The responses to chemotherapy and survival of 34 consecutive patients with germinoma-like tumors who underwent initial treatment from July 2001 to October 2010 were analyzed. The minimum apparent diffusion coefficient (minADC) value and proton magnetic resonance spectroscopy (MRS) were evaluated in recent patients. Twelve patients with histologically verified germinomas and 18 with germinoma-compatible tumors showed early logarithmic decreases in tumor volume in response to initial chemotherapy, typical low minADC values and typical MRS characteristics, including increased choline/creatine ratios, decreased N-acetylasparate/creatine ratios, and large lipid peaks. These patients had good progression-free survival. The other four patients, with histologically verified non-germinomas, showed no response to chemotherapy, and one patient with a pineoblastoma showed a similar minADC value and MRS characteristics to those of patients with germinomas. The response to initial chemotherapy can be used to distinguish germinoma-compatible tumors from non-germinoma in patients with germinoma-like tumors of the pineal and/or suprasellar regions. The evaluation of minADC and proton MRS are useful for distinguishing germinomas from other tumors. However, a subset of non-germinomas may show similar characteristics to germinomas. The benefit of bypassing unnecessary surgical intervention can be achieved, at least in Asian populations with a high incidence of germinomas.     

Awake craniotomy and multilingualism: Language testing during anaesthesia for awake craniotomy in a bilingual patient

An awake craniotomy for epilepsy surgery is presented where a bilingual patient post-operatively reported temporary aphasia of his first language (Spanish). This case report discusses the potential causes for this clinical presentation and methods to prevent the occurrence of this in future patients undergoing this form of surgery.     

Fatal glioblastoma after Gamma Knife radiosurgery for arteriovenous malformation in a child

We describe a fatal case of glioblastoma multiforme that was induced by Gamma Knife radiosurgery (GKS; Elekta AB, Stockholm, Sweden) for an arteriovenous malformation (AVM). A 4-year-old girl presented with repeated convulsions. Imaging studies revealed an AVM located in the right thalamus. One year after initial symptoms, GKS was performed to obliterate the nidus. The maximum and marginal radiation doses were 32 and 16 Gy, respectively. Seventy months after GKS, the patient represented with severe headache. MRI showed a poorly demarcated tumor with heterogeneous gadolinium enhancement in the right thalamus and adjacent to the white matter of the temporal lobe. After a generalised convulsion, the patient deteriorated into a deep coma. CT scans showed severe brain swelling with intratumoral hemorrhage. An emergency craniotomy was performed, and the hematoma was removed. During this surgery, a tumor mass, which was found adjacent to the hematoma, was resected. Microscopic examination revealed glioblastoma multiforme. Despite intensive treatment, the patient died 1 month after surgery. A GKS-induced secondary tumor is a rare but serious complication. It is important to be aware of the adverse effects of GKS, including secondary neoplasms, before its clinical application, especially in young patients.     

Risk of hypertension with regorafenib in cancer patients: a systematic review and meta-analysis

Background

Regorafenib is a novel multikinase inhibitor approved for use in metastatic colorectal cancer (mCRC) and locally advanced gastrointestinal stromal tumors (GISTs). Hypertension is one of the major adverse events of this agent, but to date the incidence and risk of hypertension with regorafenib have not been systematically investigated. We have conducted a systematic review and meta-analysis of published clinical trials to determine its overall incidence and risk.

Methods

PubMed, Web of Science and abstracts presented at the American Society of Clinical Oncology annual meetings were searched to identify relevant studies published up to September 9, 2013. Eligible studies were prospective phase II or III clinical trials using regorafenib in cancer patients with data on hypertension available. The incidence and relative risk (RR) of hypertension were calculated using a random-effects model.

Results

Data from a total of 1,069 patients (regorafenib n?=?750; controls n?=?319) from five clinical trials were included for analysis. The overall incidence of all-grade and high-grade hypertension were 44.4 % [95 % confidence interval (CI) 30.8–59.0 %) and 12.5 % (95 % CI 5.2–27.1 %), respectively. The use of regorafenib in cancer patients was associated with a significantly increased risk of all-grade (RR 3.76, 95 % CI 2.35–5.99) and high-grade (RR, 8.39, 95 % CI 3.10–22.71) hypertension. The risk might vary with tumor types (P?=?0.000).

Conclusions

Patients with cancer receiving regorafenib have a significantly higher risk of developing hypertension. Close monitoring and appropriate management of this hypertension are strongly recommended.