Limited Margins Using Modern Radiotherapy Techniques Does Not Increase Marginal Failure Rate of Glioblastoma

PURPOSE: We investigate the patterns of failure in the treatment of glioblastoma(GBM) based on clinical target volume(CTV) margin size,dose delivered to the site of initial failure,and the use of temozolomide and intensity-modulated radiotherapy(IMRT).METHODS: Between August 2000 and May 2010,161 patients with GBM were treated with radiotherapy with or without concurrent temozolomide.Patients were treated with CTV expansions that ranged from 5 to 20 mm using a shrinking field technique.Patterns of failure and time to progression and overall survival were compared based on CTV margin,use of temozolomide,and use of IMRT.Kaplan Meier analysis was used to estimate survival times,and χ test was used for comparison of cohorts.RESULTS: For patients treated with 5-,10-,and 15-to 20-mm CTV,79%,77%,and 86% experienced failures in the 60 Gy volume,respectively.Forty-eight percent,55%,and 66% of patients with 5-,10-,and 15-to 20-mm CTV experienced failures in the 46 Gy volume,respectively.There was no statistical difference between patients treated with 5-,10-,15-to 20-mm margins with regard to 60 Gy failure(P=0.76),46 Gy failure(P=0.51),or marginal failure(P=0.73).Eighty percent of patients receiving temozolomide experienced failures in the 60 Gy volume.There was no increased likelihood of marginal failures in patients receiving IMRT(P =0.97).CONCLUSIONS: Modern treatment techniques including use of concurrent temozolmide,limited CTV margin size,and IMRT have not greatly changed the patterns of failure of GBM.     

Prevalence and classification of HIV-associated oral lesions

OBJECTIVES: An International Workshop addressed the prevalence and classification of HIV/AIDS associated oral lesions.
DESIGN: Five questions provided the framework for discussion and literature review. What is the prevalence of oral lesions in children and adults? Should the accepted classification of HIV-related oral lesions be modified in the light of recent findings? Why is there a gender difference in the prevalence of oral lesions in developed and developing countries? Are there unusual lesions present in developing countries? Is there any association between modes of transmission and the prevalence of oral lesions?
RESULTS: Workshop discussion emphasized the urgent need for assistance in the development of expertise to obtain accurate global prevalence data for HIV-associated oral lesions. Oral candidiasis has been consistently reported as the most prevalent HIV-associated oral lesion in all ages. Penicilliosis marneffei, a newly described fungal infection, has emerged in South-east Asia. Oral hairy leukoplakia and Kaposi's sarcoma appear to be associated with male gender and male-to-male HIV transmission risk behaviours. These lesions occur only rarely in children.
CONCLUSIONS: Additional prevalence data are needed from developing countries prior to substantially altering the 1993 ECC/WHO Classification of oral lesions associated with adult HIV infection. The workshop confirmed current oral disease diagnostic criteria.     

经桡动脉冠状动脉介入治疗中5F与6F导引导管的对比研究

目的比较5French(5F)及6French(6F)导引导管在经桡动脉冠状动脉介入治疗(TRI)患者中的安全性及有效性。方法共纳入2009年2月至2010年3月患者,收集相关资料录入数据库,包括患者基线临床资料、导引导管的尺寸、靶血管、靶病变的特点、手术的成功率、手术失败原因、经桡动脉冠状动脉介入治疗手术的成功率及失败原因、患者住院期间主要不良心血管事件率及术后桡动脉闭塞率。结果连续纳入患者共185例,接受195次经桡动脉冠状动脉介入治疗术,平均年龄(57±11)岁(33～81岁);其中54例患者纳入6F导引导管组,共进行56次手术,治疗89处病变;138例患者纳入5F导引导管组,共行146次手术,治疗231处病变。AHA B2/C型病变比例在两组间差异无统计学意义(5F组43.7%/29.0%比6F组46.1%/34.6%,P>0.05),但慢性闭塞性病变、分叉病变、钙化病变5F组显著少于6F组(5.6%比14.6%,P=0.005;23.4%比37.1%,P=0.012;9.5%比47.2%,P<0.001);组间的手术时间[(45±21)min比(46±19)min)]、手术X线曝光时间[(15±12)min比(16±13)min]、使用造影剂量[(140±45)ml比(156±56)ml]差异均无显著统计学意义(P>0.05),但是5F组造影剂用量有减少的趋势(P=0.066);组间住院时间[(1.40±1.26)d比(1.29±0.69)d]和手术成功率(95.2%比94.6%)也差异无统计学意义(P>0.05);5F组1例患者术后桡动脉闭塞,6F组无患者术后桡动脉闭塞(P=1.0),5F组1例发生卒中。结论经桡动脉冠状动脉介入治疗,即使是复杂及高危冠脉病变,5F导引导管有效、安全,手术成功率不低于常规使用的6F导引导管;换用5F导引导管进行冠状动脉介入治疗是一种有吸引力的选择。     

Overexpression of Pim-1 during progression of prostatic adenocarcinoma

AIMS: Pim-1 is a serine/threonine kinase that has been shown to play an integral role in the development of a number of human cancers, such as haematolymphoid malignancies. Recently, evidence has shown Pim-1 to be important in prostatic carcinogenesis. In order to further our understanding of its role in prostate cancer, we investigated Pim-1 expression in normal, premalignant, and malignant prostate tissue. METHODS: Using immunohistochemistry, Pim-1 expression was analysed in prostate tissue from 120 radical prostatectomy specimens. In each case, Pim-1 staining was evaluated in benign prostatic epithelium, high grade prostatic intraepithelial neoplasia (PIN), and prostatic adenocarcinoma. The number of positively staining cells was estimated, and the intensity of staining was scored on a scale of 0 to 3+. RESULTS: Pim-1 immunoreactivity was identified in 120 cases (100%) of adenocarcinoma, 120 cases (100%) of high grade PIN, and 62 cases (52%) of benign glands. The number of cells staining in benign epithelium (mean 34%) was much lower than that in high grade PIN (mean 80%; p<0.0001) or adenocarcinoma (mean, 84%; p<0.0001). There was no significant difference between high grade PIN and adenocarcinoma in the percentage of cells staining positively for Pim-1 (p = 0.34). The staining intensity for Pim-1 was significantly lower in benign prostatic epithelium than in PIN and adenocarcinoma (p<0.001). There was no statistically significant correlation between the level of Pim-1 expression and Gleason score, patient age, tumour stage, lymph node metastasis, perineural invasion, vascular invasion, surgical margin status, extraprostatic extension, or seminal vesicle invasion. CONCLUSIONS: Pim-1 expression is elevated in PIN and prostatic adenocarcinoma compared with benign prostatic epithelium. This finding suggests that upregulation of Pim-1 may play a role in prostatic neoplasia.     

Chaperonin-mediated assembly of wild-type and mutant subunits of human propionyl-CoA carboxylase expressed in Escherichia coli

We developed a bacterial expression system for the human alpha and beta cDNAs of propionyl-CoA carboxylase (PCC). These cDNAs (less the putative mitochondrial matrix targeting presequences) were co-expressed in Escherichia coli on one plasmid vector with each cDNA having its own IPTG-inducible promoter. Only negligible amounts of active PCC were measured despite the presence of both alpha and beta subunits as indicated by Western blot analysis and the almost complete biotinylation of the alpha subunit. Co-expression of this plasmid with a second plasmid vector over-expressing the E. coli chaperonin proteins, groES and groEL, resulted in a several hundred-fold increase in PCC specific activity, to a level comparable with that found in crude human liver extracts. PCC was partially purified on monomeric avidin affinity resin and the presence of both alpha and beta subunits was demonstrated, thereby confirming the assembly of both subunits into an active enzyme. Deficiency of either alpha PCC or beta PCC results in propionic acidemia, an autosomal recessive disorder. We used this expression system to characterize one missense mutation previously described in five Japanese alleles, namely C1283T (Thr428lle) in beta PCC. This mutation, when expressed in E.coli under the same conditions as that of wild-type PCC, had null activity, despite the presence of assembled alpha PCC and beta PCC subunits. This bacterial expression system can be useful for analysis of either alpha PCC or beta PCC mutations. Our findings indicated that the groES and groEL chaperonin proteins were essential for folding and assembly of the human PCC heteromeric subunits.      

A prospective study of blood donations in healthy elderly persons

Iron stores were observed in 57 healthy elderly volunteers, between 63 and 77 years of age, who donated 5 units of blood over approximately 1 year. An equal number of nondonors who contributed approximately 7 mL of blood at each visit for iron status measurements only were seen at the same frequency as the donor population. At entrance to the study, iron stores in women and men averaged 724 and 875 mg, respectively. After five donations, mean iron stores dropped to 67 mg in women (n = 27) and 362 mg in men (n = 30); four women (15%) became iron deficient, while two (7%) developed iron deficiency anemia. Three men (10%) developed iron deficiency, but none were found to be anemic. Mean intakes of iron were 23.3 and 22.5 mg per day, respectively, for women and men. Iron intakes were adequate to meet iron requirements of nondonors, but they were not sufficient to halt the steady decrease in iron stores among the donor population, in whom iron absorption increased from approximately 5 percent at entrance to 14 percent at the time of the fifth donation. In summary, healthy elderly persons may contribute to the national blood resource; however, donations should probably be limited to less than five per year or donors should regularly take an iron supplement to preserve reasonable amounts of iron reserves.     

39Gastrointestinal electrical stimulation in post-surgical gastroparesis improves symptoms independently while gastric emptying response is dependent on baseline emptying

Introduction:  Temporary GES (tempGES) can improve both gastric emptying and symptoms in post-surgical gastroparesis (PS-GP). (SSAT 2004). Long-term effects on GI symptoms and gastric emptying are unknown. Since many PS-GP patients have non-delayed emptying, the long-term effect on baseline normal or rapid emptying is also unknown.
Patients:  36 pts (6 M, 30 F, mean age 42 years) with post-surgical: Bilroth I ( n  = 11), Bilroth II ( n  = 4), other gastric surgery ( n  = 21) disordered gastric emptying were evaluated.
Methods:  GI symptoms (vomiting = V, Total = TSS), and solid meal gastric emptying (GET) at 1 and 4 h, were compared at baseline (Base), after temporary (tempGES) and permanent (permGES) gastric electrical stimulation as previously described (NGM, 2004; 16: 635.) Long-term follow-up for permanent GES ranged from 6 month to 10 years. Results were compared by t-tests, and are reported as means ± SEM.
Results:  29 of the 36 patients were able to tolerate food for baseline quantitative gastric emptying testing. 20 patients had delayed and 9 patients had non-delayed gastric emptying, with 7/9 being rapid. With both tempGES and permGES, GI symptoms improved (p < 0.05). Both tempGES and permGES showed accelerated GET for delayed patients and generally slowed GET for non-delayed (p < 0.05 for 1 h values). See tables below.
Conclusions:  In a large group of post-surgical GP patients, temporary and permanent gastrointestinal electrical stimulation improved GI symptoms independent of gastric emptying and for a prolonged time. GES improves symptoms independent of baseline gastric emptying, and improves GET dependent on the baseline gastric emptying.
 

     

Gestational exposure to chlorpyrifos: dose response profiles for cholinesterase and carboxylesterase activity

This study investigates the in vivo dose response profiles of the target enzyme cholinesterase (ChE) and the detoxifying enzymes carboxylesterase (CaE) in the fetal and maternal compartments of pregnant rats dosed with chlorpyrifos [(O,O'-diethyl O-3,5,6-trichloro- 2-pyridyl) phosphorothionate], a commonly used organophosphorus insecticide. Pregnant rats were dosed daily (po) with chlorpyrifos in corn oil (0, 3, 5, 7, or 10 mg/kg) on gestational days (GD) 14-18. Animals were sacrificed 5 h after the last chlorpyrifos dose (time of maximum brain cholinesterase inhibition) for analysis of ChE and CaE activity in maternal blood, liver, brain, placenta, and fetal liver and brain. The in vitro sensitivity (i.e., IC50, 30 min, 26 degrees C) of CaE also was determined by assaying the activity remaining after incubation with a range of chlorpyrifos-oxon concentrations. In vivo exposure to 10 mg/kg chlorpyrifos from GD14-18 caused overt maternal toxicity, with dose-related decreases in ChE activity more notable in maternal brain than fetal brain. Dose-related effects were also seen with chlorpyrifos-induced inhibition of fetal liver ChE and maternal brain CaE activities. Gestational exposure caused no inhibition of placental ChE or CaE, fetal brain CaE, or maternal blood CaE. ChE activities in the maternal blood and liver, as well as fetal and maternal liver CaE, however, were maximally inhibited by even the lowest dosage of chlorpyrifos. The in vitro sensitivity profiles of CaE to chlorpyrifos-oxon inhibition were valuable in predicting and verifying the in vivo CaE response profiles. Both the in vivo and in vitro findings indicated that fetal liver CaE inhibition was an extremely sensitive indicator of fetal chlorpyrifos exposure.