Stereotactic radiosurgery with adjusted linear accelerator for cerebral arteriovenous malformations: preliminary results in the Netherlands]

OBJECTIVE: To assess the effects of stereotactic radiosurgery of a cerebral arteriovenous malformation (AVM). DESIGN: Prospective. METHOD: In November 1991-December 1995 linear acceleration radiosurgery was performed on 29 patients for their 30 cerebral AVMs in the University Hospital Vrije Universiteit, Amsterdam, the Netherlands. There were 15 females and 14 males with a mean age of 37.1 years (range: 13-58). Generally one isocentre was used and 15 Gy was given to the margins of the AVM at the 80% isodose. The mean target volume was 2.4 ml (range; 0.5-8.2). After 6 months, one year and thereafter every year, neurological and MRI-controls took place, in the outpatient ward. Angiography was performed after an average of 35 months (range: 24-70) to check if the AVM had obliterated. RESULTS: Angiographic post-treatment results were available in 27 patients and MRI information in one. Angiographic obliteration occurred in 20 patients (71%). No permanent radiation-induced neurological deficit was seen, nor did any hemorrhage occur during the interval between irradiation and obliteration.     

Arteriovenous malformations: study about 54 patients

BACKGROUND: Arteriovenous malformation (AVM) are vascular anomalies that may threaten functional and vital prognosis. The aim of this study was to assess the managment of Arteriovenous malformation METHODS: It is a retrospective study about 54 patients, having AVM, collected over a 7-year period. RESULTS: Sex ratio MJF was 1.25; average age at the diagnosis was 25.4 years. Puberty, pregnancy and trauma, were the most important favoring factors for the development of AVM. Location was the head in 75% of the cases. Doppler ultrasound was the most indicated examination to confirm the diagnosis. In over than 70% of our patients, therapeutic abstention and follow-up were indicated. In the other cases, embolization, with or without surgery was the treatment. A patient died of massive haemorrhage. Treatment is necessary in complicated AVM. Follow-up (if abstention or after treatment) is mainly based on clinical and Doppler data. CONCLUSIONS: AVM are anomalies that may be serious and their management must be multidisciplinary, to allow better therapeutic indications.     

Radiosensitivity of peripheral blood lymphocytes obtained from patients with cancers of the breast, head and neck or cervix as determined with a micronucleus assay

The in vitro radiation sensitivities of peripheral blood lymphocytes obtained from 48 normal females and 168 female cancer patients were measured with the cytokinesis-blocking micronucleus assay. Cancer patients group had significantly higher mean baseline micronucleus frequency than normal healthy controls. Breast cancer patients were more radiosensitive than normal individuals. Cervical cancer cases were less radiation sensitive than normal subjects. The relative lack of radiation sensitivity in cervical-cancer cases could be due to modification of the radiosensitivity of patients' immune-responsible cells by human papillomaviruses infection. Normal individuals and cancer patients were classified according to their radiation sensitivity which was evaluated with the radiation-induced micronucleus frequencies. Such a classification will be an important initial step to characterize the radiosensitive, radioresistant, or cancer-prone individuals using specific SNP typing.     

Evaluation of in vitro genotoxic activity of bleomycin and mitomycin C in human lymphocytes using the alkaline comet assay

Although chemotherapy targets cancer tissue, it also damages the DNA of non-cancer cells. The aim of this study was to evaluate the in vitro genotoxic potential of therapeutic concentrations of bleomycin and mitomycin C, added alone or in combination to cultures of human peripheral lymphocytes. The levels of DNA damage and repair were assessed using the alkaline comet assay immediately after cell treatment as well as 24 and 48 hours following treatment. The results indicate that individual drugs and their combination induce a significant DNA damage to peripheral blood lymphocytes. Bleomycin alone induced the highest levels of primary DNA damage immediately after cell treatment. Although mitomycin C alone induced massive cross-linking and retarded DNA migration in resting cells, active proliferation and repair processes significantly increased DNA damage. Combined, they showed a synergetic effect, inducing complex patterns of DNA damage in peripheral blood lymphocytes and producing different types of lesions and a number of DNA alterations that directly or indirectly increased DNA migration. Our study has confirmed the sensitivity of the alkaline comet assay for assessing bleomycin and/or mitomycin C genotoxicity to human lymphocytes at concentration levels used in clinic. It has also demonstrated the utility of the alkaline comet assay as one of the primary screening methods for in vitro studies of drug-DNA interactions, especially in studying mechanisms of action of new drugs.     

脑动静脉畸形介入治疗的临床护理体会

目的：分析研究脑动静脉血管畸形（AVM）患者进行介入治疗时,术前和术后的护理过程,探讨护理对减少介入治疗脑动静脉畸形并发症和提高患者预后生存质量的价值。方法：选择22例应用血管内栓塞治疗的AVM患者,同时进行密切护理,术前详细评估病情,做好术前心理护理;术后采取相应的护理措施。结果：22例患者中,20例患者栓塞治疗成功,成功率为90.91%。完全栓塞18例,完全成功率81.82%;1例栓塞90%以上,成功率为4.55%。1例发生过度灌注综合征,占4.55%;无脑出血患者,患者原有症状明显减轻或消失,未出现其他严重并发症。结论：术前充分准备和术后严密的病情观察及周密细致的护理,是颅内AVM患者介入治疗成功的保障。     

脑动静脉畸形破裂出血急性期的手术治疗

目的总结脑动静脉畸形（AVM）破裂出血急性期的外科治疗经验。方法回顾分析1999年1月—2006年12月37例AVM破裂出血患者急性期的不同治疗方法和疗效。结果1期血肿清除＋AVM显微切除术19例；1期单纯血肿清除＋2期AVM显微切除术10例；血肿清除＋γ刀治疗2例；血肿清除＋栓塞术1例；双侧脑室外引流5例。2例死亡，1例昏迷，其余患者神经功能较术前均有不同程度的改善。结论脑AVM出血急性期的外科治疗，应清除血肿和酌情妥善处理AVM畸形血管团，达到改善症状和解除病因的双重目的。     

Functional analysis of XRCC4 mutations in reported microcephaly and growth defect patients in terms of radiosensitivity

Non-homologous end joining is one of the main pathways for DNA double-strand break (DSB) repair and is also implicated in V(D)J recombination in immune system. Therefore, mutations in non-homologous end-joining (NHEJ) proteins were found to be associated with immunodeficiency in human as well as in model animals. Several human patients with mutations in XRCC4 were reported to exhibit microcephaly and growth defects, but unexpectedly showed normal immune function. Here, to evaluate the functionality of these disease-associated mutations of XRCC4 in terms of radiosensitivity, we generated stable transfectants expressing these mutants in XRCC4-deficient murine M10 cells and measured their radiosensitivity by colony formation assay. V83_S105del, R225X and D254Mfs^*68 were expressed at a similar level to wild-type XRCC4, while W43R, R161Q and R275X were expressed at even higher level than wild-type XRCC4. The expression levels of DNA ligase IV in the transfectants with these mutants were comparable to that in the wild-type XRCC4 transfectant. The V83S_S105del transfectant and, to a lesser extent, D254Mfs^*68 transfectant, showed substantially increased radiosensitivity compared to the wild-type XRCC4 transfectant. The W43R, R161Q, R225X and R275X transfectants showed a slight but statistically significant increase in radiosensitivity compared to the wild-type XRCC4 transfectant. When expressed as fusion proteins with Green fluorescent protein (GFP), R225X, R275X and D254Mfs^*68 localized to the cytoplasm, whereas other mutants localized to the nucleus. These results collectively indicated that the defects of XRCC4 in patients might be mainly due to insufficiency in protein quantity and impaired functionality, underscoring the importance of XRCC4’s DSB repair function in normal development.     

Effect of an inhibitor of PGE (flurbiprofen) on colony growth from normal and leukemic peripheral leukocytes in basal conditions and in presence of testosterone or cortisol

The Authors have controlled the colony growth in coltures from peripheral leukocytes of normal subjects and from patients with CML and AML. The cultures were prepared on double agar layer in basal conditions and after adding flurbiprofen and/or cortisol and/or testosterone. The exam of the plates has shown a light similar stimulating activity on the growth of all substances separately considered, with and evidence ability of flurbiprofen of potentiate the action of the two hormones, both in coltures from normal and leukemic peripheral leukocyte CFU-GM.     

Cytogenetic radiosensitivity of g0-lymphocytes of breast and esophageal cancer patients as determined by micronucleus assay

Enhanced chromosomal radiosensitivity is a feature of many cancer predisposition conditions, indicative of the important role of chromosomal alterations in carcinogenesis. In this study the cytokinesis-blocked micronucleous assay was used to compare the radiosensitivity of blood lymphocytes obtained from Iranian breast or esophageal cancer patients (n = 50, n = 16; respectively) with that of control individuals (n = 40). For each sample, one thousand binucleate lymphocytes were analyzed before and after in vitro exposure to 3 Gy of gamma rays. The radiation-induced frequency of micronucleus was significantly higher in the breast cancer group (261/1,000 binucleated cells) than in esophageal cancer group (241/1,000 binucleated cells, P < 0.01) or in the control group (240/1,000 binucleated cells, P < 0.01). The results indicate that breast cancer patients are more radiosensitive compared to normal healthy individuals or esophageal cancer patients. Increased radiosensitivity could be due to defects in DNA repair genes involved in breast cancer formation. Since patients with esophageal cancer did not show elevated radiosensitivity, it is assumed that the contribution of radiosensitivity-related genes to the development of esophageal cancer may be smaller than the contribution of those genes to breast cancer.     

广西瑶、侗、苗、壮等民族外周血白细胞中BK病毒的研究

目的了解广西瑶、侗、苗、壮等少数民族外周血白细胞中多瘤病毒BKV的感染情况，掌握该区人群BKV的携带情况，阐明BKV在人体内的传播方式。方法于2006年1月-2008年5月采集广西瑶、侗、苗、壮等少数民族及汉族健康人外周血标本各2500份，提取淋巴细胞基因组DNA，用巢式PCR方法扩增BKV的保守区编码序列，统计分析不同少数民族、年龄、性别组BKV—DNA检出率。结果2500份健康人外周血白细胞（PBLs）样品中BKV—DNA序列检出率为60．6％，不同民族、性别、年龄组之间无显著性差异（P〉0．05）。结论BKV在广西瑶、侗、苗、壮等少数民族及汉族健康人PBLs中存在较高的感染率，本研究证实了PBLs是BKV在体内的潜伏细胞及传播载体，应加强对BKV条件致病性的认识，积极防治、减少BKV相关性肾病（BKVN）的发生率。     

Individual differences in the radiosensitivity of hematopoietic progenitor cells detected in steady-state human peripheral blood

The aim of this study is to evaluate the individual differences in radiosensitivity of lineage-committed myeloid hematopoietic progenitors, colony-forming cells (CFC), detected in steady-state human peripheral blood (PB). Mononuclear cells were prepared from the buffy-coat of 30 individuals PB, and were assayed for CFC by semi-solid culture supplemented with cytokines. X irradiation was performed in the range of 0.5-4 Gy at a dose rate of about 80 cGy/min. The mean number of hematopoietic progenitor cells is 5866 alpha 3408 in 1 ml of buffy-coat, suggesting that the erythroid progenitor cells are the major population. The total CFC radiosensitivity parameter D(0) and n value are 1.18 alpha 0.24 and 1.89 alpha 0.98, respectively. Using a linear regression analysis, a statistically significant correlation is observed between the D(0) value and the surviving fraction at 4 Gy (r = 0.611 p < 0.001). Furthermore, we evaluate the relationship between individual radiosensitivity and the level of antioxidants, plasma uric acid, plasma bilirubin, and intracellular glutathione. No statistically significant correlations are observed, however, between the D(0) parameter and the level of antioxidants, plasma uric acid, plasma bilirubin, and intracellular glutathione. The present study demonstrates that there are large individual differences in the radiosensitivity of hematopoietic progenitor cells as detected in steady-state human PB. These differences demonstrate almost no correlation with plasma or intracellular antioxidants. The prediction of individual differences in radiosensitivity of CFC can only be measured by 4 Gy irradiation.     

单细胞凝胶电泳方法评价肿瘤细胞辐射敏感性研究

目的 探讨单细胞凝胶电泳用于肿瘤细胞辐射敏感性检测的可行性。方法 选取三种不同肿瘤细胞株:肝癌细胞(HepG₂)、食管癌细胞(EC-9706)和乳腺癌细胞(MCF-7)。采用MTT法检测肿瘤细胞经γ射线照射后的存活分数(SF);单细胞凝胶电泳(Single cell gel electrophoresis,SCGE)检测肿瘤细胞的DNA断裂水平。结果 MTT法:2Gy、4Gy和8Gy照射后,HepG₂和EC-9706的SF显著低于MCF-7,表明HepG₂和EC-9706细胞具有更高的辐射敏感性。SCGE:三种肿瘤细胞在8Gy照后表现出的辐射敏感性差别最显著。结论 多种生物学指标的综合应用,有希望更加客观准确地评价肿瘤细胞的辐射敏感性。     

术中超声在神经外科的应用初探

目的应用术中超声观察颅内占位性病变的回声特征,探讨术中超声在颅脑手术中的应用价值。方法行术中超声应用常规,对38例行颅脑手术的患者应用术中超声检查,分别在:(1)打开硬脑膜后;(2)外科医师认为完成病灶切除后,两个时段对病灶及周围组织观察,记录。结果颅内肿瘤、血肿、异物多呈高回声,肿瘤病理特征不同,其声像图表现亦不同,明确判断肿瘤的大小、边界、位置、与周边脑组织及血管关系等情况。AVM术中超声应用可协助术者确定供血动脉和引流静脉;囊性占位术中超声可引导穿刺抽吸减压;颅内异物术中超声可明确判断异物形态大小位置数量;在病灶切除后可观察残留情况。结论术中超声可协助外科医师明确病灶边界,准确定位,提供病灶周围手术危险因素,协助提高手术精确性;显示病灶内细微情况以明确病灶性质;协助外科医师发现残留病灶以提高手术全切率。     

焦炉工尿中1-羟基芘水平与早期遗传学效应的关系

目的 研究焦炉工尿中1-羟基芘水平与外周血淋巴细胞胞质分裂阻滞微核和彗星尾矩间的关系。方法 分别选取133名焦炉作业工人和28名非职业暴露人员,使用碱水解-高效液相色谱法测定尿中1-羟基芘浓度作为个体多环芳烃暴露内剂量,分别应用彗星试验和胞质分裂阻滞微核法评价了研究对象外周血淋巴细胞DNA和染色体损伤,使用调查表收集职业暴露史、年龄、性别、吸烟和饮酒状况等信息。结果 调整了年龄、性别、吸烟和饮酒状况后,尿中1-羟基芘浓度与外周血淋巴细胞微核细胞率和彗星尾矩均存在良好的相关关系。进一步按尿中1-羟基芘水平将研究对象分成0．30～2．44(54人)、2．45～7．09(53人)和7．10～33．10μmol／mol肌酐组(54人)3个内剂量组,3组个体尿中1-羟基芘的几何均值分别为1．14、4．32和12．49μmol／mol肌酐。使用多元非参数协方差分析校正了不同内剂量组个体的年龄、性别、吸烟和饮酒状况后,7．10～33．10μmol／mol肌酐组的彗星尾矩(中位数3．67)显著性高于2．45～7．09和0．30～2．44μmol／mol肌酐组(中位数分别为1．68和1．12),但后2组之间差异无显著性;2．45～7．09和7．10～33．10μmol／mol肌酐组微核率的中位数分别为8．00‰和7．50‰,2组间的差异无显著性,但均显著高于0．30～2．44μmol／mol肌酐组的6．00‰。结论 外周血淋巴细胞的彗星尾矩较胞质分裂阻滞微核能更好地反映多环芳烃暴露导致的早期遗传学效应。     

Chromosome fragments have the potential to predict hyperthermia-induced radio-sensitization in two different human tumor cell lines

Cellular radiosensitivity, assessed by loss of clonogenicity, has been shown to correlate with the number of radiation-induced chromosomal aberrations. Also an increased radiosensitivity by hyperthermia has been shown to correlate with an increase in chromosomal aberrations. Therefore, determination of the number of chromosomal aberrations might be used as an assay to predict the radiosensitivity of tumors pre-treated with hyperthermia at clinically relevant temperatures. The use of premature chromosome condensation combined with fluorescent in situ hybridisation (PCC-FISH) has been shown to be clinically applicable. Therefore, the use of chromosomal aberrations as determined with PCC-FISH for the prediction of hyperthermia-induced radio-sensitization in human tumor cells was investigated. Confluent cultures of SW-1573 (human lung carcinoma) and RKO (human colorectal carcinoma) cells were treated with 1 h 41 degrees C or 43 degrees C hyperthermia prior to gamma-irradiation. Clonogenic cell survival and induction of chromosomal aberrations (unrejoined chromosomal fragments and translocations), by PCC-FISH, were studied at 24 h after treatment. Pre-treatment with hyperthermia at 41 degrees C for 1 h enhanced the radiosensitivity of RKO cells but not of SW-1573 cells. Increasing the temperature to 43 degrees C for 1 h enhanced the radiosensitivity of SW-1573 cells. When radio-sensitization was observed, a significant increase in the number of unrejoined chromosomal fragments was found but the frequency of translocations was not increased. Hyperthermia-induced radio-sensitization is correlated with an increase in unrejoined chromosomal fragments. This suggests that determination of the number of chromosomal fragments after hyperthermia and radiation treatment might be used for the prediction of combined treatment response in cancer patients.     

Early increase of radiation-induced γH2AX foci in a human Ku70/80 knockdown cell line characterized by an enhanced radiosensitivity

A better understanding of the underlying mechanisms of DNA repair after exposure to ionizing radiation represents a research priority aimed at improving the outcome of clinical radiotherapy. Because of the close association with DNA double strand break (DSB) repair, phosphorylation of the histone H2AX protein (γH2AX), quantified by immunodetection, has recently been used as a method to study DSB induction and repair at low and clinically relevant radiation doses. However, the lack of consistency in literature points to the need to further validate the role of H2AX phosphorylation in DSB repair and the use of this technique to determine intrinsic radiosensitivity. In the present study we used human mammary epithelial MCF10A cells, characterized by a radiosensitive phenotype due to reduced levels of the Ku70 and Ku80 repair proteins, and investigated whether this repair-deficient cell line displays differences in the phosphorylation pattern of H2AX protein compared to repair-proficient MCF10A cells. This was established by measuring formation and disappearance of γH2AX foci after irradiating synchronized cell populations with (60)Co γ-rays. Our results show statistically significant differences in the number of γH2AX foci between the repair-deficient and -proficient cell line, with a higher amount of γH2AX foci present at early times post-irradiation in the Ku-deficient cell line. However, the disappearance of those differences at later post-irradiation times questions the use of this assay to determine intrinsic radiosensitivity, especially in a clinical setting.     

Intrauterine undernutrition in rats interferes with leukocyte migration, decreasing adhesion molecule expression in leukocytes and endothelial cells

Experimental and epidemiologic data have shown that malnutrition predisposes individuals to infections. Immune responses are compromised, particularly in undernourished children. Therefore, we investigated the migratory capacity of leukocytes, using the intravital microscopy technique, in male Wistar rats (8-9 wk of age) that were undernourished in utero after their dams were fed 50% less food than the amount consumed by control dams. The number of leukocytes rolling along the venular endothelium, sticking after stimulation with leukotriene B4, tumor necrosis factor-alpha (TNF-alpha) or zymosan-activated plasma, or migrating after TNF-alpha stimulation was significantly reduced in the undernourished rat offspring. Compared with nourished rat offspring, undernourished offspring had significantly reduced numbers of circulating leukocytes, higher blood pressure, and higher leukocyte rolling velocity (V(WBC)), as well as a higher ratio between V(WBC) and RBC velocity (V(RBC)). Endothelial P-selectin and intercellular adhesion molecule-1 (ICAM-1) expression, analyzed by immunohistochemistry, and basal leukocyte L-selectin expression, analyzed by flow cytometry, were significantly reduced in the undernourished rat offspring. Because the groups did not differ in leukocyte CD11/18 expression, endothelial expression of platelet-endothelial cell adhesion molecule-1, or venular blood flow velocity and, consequently, venular shear rate, we conclude that intrauterine undernutrition in rats reduces leukocyte migration, downregulates endothelial expression of P-selectin and ICAM-1, as well as leukocyte expression of L-selectin, while reducing leukocyte counts. The higher V(WBC) and V(WBC)/V(RBC) ratio may also play a role in this reduced leukocyte migration. Our data suggest that this phenomenon is involved in the increased predisposition to infections in undernourished subjects.     

An 11 year follow-up of individual radiation responses as assessed by micronuclei induction in peripheral blood lymphocytes.

In this short note we describe the results of a unique 11 year follow-up of the induction of micronuclei by radiation in three individuals. These individuals were all part of two larger studies carried out in 1987 and 1998 respectively, each having similar population characteristics. No significant differences in the average radiation response of these two populations were observed, nor were there any apparent differences in the 1987 and 1998 responses of two of the three individuals reassessed. Data from the third individual (and from a wider study reported elsewhere) do, however, provide some evidence for an age dependence. It is concluded that significant individual variations in the age-dependent responses to radiation may exist, and that while for some individuals there is no increase in radiosensitivity with age, for others there is. Such age dependences may be diluted by studying age-related responses in whole populations of limited size rather than by following individuals over a long period of time. The results reported here are from a limited data set and it is important that further studies are carried out to provide evidence for or against the existence of an age-dependent response to radiation in some individuals.     

健康成人外周血白细胞中BK病毒-DNA的研究

目的检测健康成人外周血白细胞(PBLs)中BK病毒(BKV)的感染率,探讨BKV的医院感染. 方法根据BKV保守的大T抗原(TAg)编码区序列合成引物,半套式PCR(snPCR)扩增100例健康成人PBLs样本中的BKV-DNA,统计分析不同年龄、性别组BKV-DNA的检出率及其差别. 结果 100例健康成人PBLs样本中BKV-DNA序列检出率为45%,不同年龄、性别组之间差异无显著性(P>0.05). 结论健康人PBLs是BKV在体内潜伏的重要贮主和传播运载体,BKV是重要的医院感染病原体之一.     

Smoking and subarachnoid haemorrhage

An enquiry was made into the smoking habits of 199 patients who had survived a subarachnoid haemorrhage (SAH). Information was obtained from 189, giving a 95% response rate. Those with a cerebral aneurysm had on average smoked considerably more cigarettes daily than those with arteriovenous malformations (AVM) or with normal angiographic findings (NAF) whose smoking habits were similar to those of the UK population. SAH due to cerebral aneurysm should be considered another smoking-related disease.