小分割分次立体定向放射治疗脑转移瘤近期疗效观察

目的观察小分割分次立体定向放射治疗(fractionated stereotatic radiation therapy,FSRT)脑转移瘤的近期疗效.方法15例病人单纯全脑外照射(WBRT组),中间平面剂量20～40Gy/10～20次/2～4周.17例病人接受FSRT(FSRT组),每次分次剂量为2.5～3.0Gy.其中11病人行单纯FSRT,中心总剂量为30～60Gy/1 0～20次/2～4周;6例病人先行WBRT,然后行FSRT,中心总剂量为46～60Gy/5～6周.结果KSP评分增加10分以上者,WBRT组为5 3.3%,FSRT组为82.4%.(P＜0.05).WBRT组有效率(CR PR)为50.0%;FSRT组有效率(CR PR)为80.0%.中位生存率:WBRT组为3.5月,FSRT组为10.0月.结论FSRT能有效地控制脑转移瘤,减轻神经系统症状,提高生存质量,延长病人生存期,而没有增加副作用,值得临床推广应用.     

Comparative mouse skin tumorigenicity and induction of Ha-ras mutations by bay region diol epoxides of 5-methylchrysene and 5,6- dimethylchrysene

We compared the tumor-initiating activities toward mouse skin of two structurally related polycyclic aromatic hydrocarbon diol epoxides: racemic anti-1,2,3,4-tetrahydro-5,6-dimethylchrysene-1,2-diol-3,4- epoxide (5,6-diMeCDE) and racemic anti-1,2,3,4-tetrahydro-5- methylchrysene-1,2-diol-3,4-epoxide (5-MeCDE). Tumors induced by these diol epoxides were analysed for mutations in the Ha-ras gene. 5,6- diMeCDE is derived from the non-planar parent compound 5,6- dimethylchrysene, and reacts to approximately equal extents with dA and dG in DNA, whereas 5-MeCDE is derived from a nearly planar parent compound, 5-methylchrysene, and reacts mainly with dG in DNA. 5,6- diMeCDE, at initiating doses of 33, 100 or 400 nmol per mouse, induced 1.2, 2.2 and 6.2 skin tumors per mouse, respectively. It was significantly less tumorigenic than 5-MeCDE which induced 3.1, 7.5 and 9.1 skin tumors per mouse at the same doses. Tumors induced by 5,6- diMeCDE had a large number of CAA-->CTA mutations in codon 61 of the Ha- ras gene: 50, 55 and 75% of the tumors analysed had this mutation at the 33, 100 and 400 nmol doses. No mutations were found in codons 12 and 13 in the tumors induced by 5,6-diMeCDE. In contrast, CAA-->CTA mutations in codon 61 were rarely seen in tumors induced by 5-MeCDE. At the highest dose of 5-MeCDE, 20% of the tumors analysed had mutations at G of codons 12 and 13. The results of this comparative study support the hypothesis that mutations in the Ha-ras gene in mouse skin tumors induced by PAH diol epoxides occur as a result of their direct reaction with the gene. However, pathways other than the commonly observed Ha- ras codon 61 mutations are clearly important in mouse skin tumorigenesis by these diol epoxides.      

Radiation damage to triplex DNA induced by gamma-rays: a footprinting study and Monte Carlo simulation

PURPOSE: This study is aimed at comparing the radiosensitivity of a 21-mer DNA fragment in duplex and triplex form (Py x Pu duplex and Py x Pu:Py triplex) and to give insights into the fine structural features due to the different strandedness. MATERIALS AND METHODS: The triplex sample was characterized by means of electrophoretic mobility, circular dichroism spectra and UV melting experiments. Triplex and duplex, labelled on the homopyrimidine or homopurine strand, were irradiated with 60Co gamma-rays. The samples were analysed by sequencing gel electrophoresis and the patterns of relative probabilities of frank strand breakage (FSB) and alkali-revealed breakage (ARB) at each nucleotide site were determined. Relative probabilities of OH* radical attack to duplex and triplex DNA built up with a molecular modelling software were calculated using a previously reported simulation procedure (Sy et al. 1997). The experimental data were compared with the results of the theoretical simulations of OH* radical attack to DNA. RESULTS: Globally, the duplex is more attacked than the triplex, mainly in the Pu strand. Sequence-dependent variations of FSB and FSB+ARB probabilities in both duplex and triplex were revealed. No significant differences between the patterns of damage in the triplex and in the duplex were observed. CONCLUSIONS: The presence of the third Py strand located in the major groove of the DNA duplex modifies the total yields of radiation-induced DNA damage, but not the sequence-dependent patterns of relative probability of damage at each nucleotide site.     

Detection of alkaline sphingomyelinase activity in human stool: proposed role as a new diagnostic and prognostic marker of colorectal cancer.

OBJECTIVES: Intestinal alkaline sphingomyelinase, by exerting a major role in dietary sphingomyelin digestion, is responsible for the generation of messengers able to trigger the rapid turnover and apoptosis in intestinal epithelial cells. Markedly reduced mucosal alkaline sphingomyelinase activity has been associated with human colorectal neoplasms. The aim of this study was to analyze the alkaline sphingomyelinase activity in feces from healthy subjects and colorectal adenocarcinoma patients and to correlate it with the enzyme activity in intestinal tissues. MATERIALS AND METHODS: The enzyme activity was measured both in the intestinal samples from 12 healthy controls and 51 patients with colorectal adenocarcinoma (tumoral and paratumoral tissue) and in the fecal samples of 34 healthy subjects and 29 patients with adenocarcinoma. The relation between sphingomyelinase activity and Dukes' stage, cell differentiation degree, age, and gender was also analyzed. RESULTS: Alkaline sphingomyelinase was significantly decreased (P < 0.001; mean reduction >90%) in tumoral intestinal mucosa of patients compared with controls independently of Dukes' stage and tumor differentiation grade. Interestingly, the enzyme activity in histologically normal paratumoral tissues was statistically lower than control samples (P < 0.001). As occurs in neoplastic tissues, a relevant mean reduction (P < 0.0001; almost 90%) of alkaline sphingomyelinase was revealed in stool samples from tumor patients when compared with controls. CONCLUSION: These findings may have implications for cancer biology and perhaps also for the design of clinical test, thus suggesting that the fecal sphingomyelinase activity could really reflect the human intestinal mucosa enzyme level and could represent a new marker for human colorectal adenocarcinoma, mainly taking into account its early appearance in intestinal neoplasms.     

Determinants of Postoperative Outcomes of Female Genital Fistula Repair Surgery

OBJECTIVE:: To determine predictors of fistula repair outcomes 3 months postsurgery. METHODS:: We conducted a multicountry prospective cohort study between 2007 and 2010. Outcomes, measured 3 months postsurgery, included fistula closure and residual incontinence in women with a closed fistula. Potential predictors included patient and fistula characteristics and context of repair. Multivariable generalized estimating equation models were used to generate adjusted risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS:: Women who returned for follow-up 3-month postsurgery were included in predictors of closure analyses (n=1,274). Small bladder size (adjusted RR 1.57, 95% CI 1.39-1.79), prior repair (adjusted RR 1.40, 95% CI 1.11-1.76), severe vaginal scarring (adjusted RR 1.56, 95% CI 1.20-2.04), partial urethral involvement (adjusted RR 1.36, 95% CI 1.11-1.66), and complete urethral destruction or circumferential defect (adjusted RR 1.72, 95% CI 1.33-2.23) predicted failed fistula closure. Women with a closed fistula at 3-month follow-up were included in predictors of residual incontinence analyses (n=1,041). Prior repair (adjusted RR 1.37, 95% CI 1.13-1.65), severe vaginal scarring (adjusted RR 1.35, 95% CI 1.10-1.67), partial urethral involvement (adjusted RR 1.78, 95% CI 1.27-2.48), and complete urethral destruction or circumferential defect (adjusted RR 2.06, 95% CI 1.51-2.81) were significantly associated with residual incontinence. CONCLUSION:: The prognosis for genital fistula closure is related to preoperative bladder size, previous repair, vaginal scarring, and urethral involvement. LEVEL OF EVIDENCE:: II.     

Development and feasibility of a sedentary behavior intervention for stroke: a case series

Background and Objective: High levels of sedentary behavior are prevalent among people with stroke and contribute to elevated risk for recurrent stroke. Few interventions reduce sedentary behavior post-stroke. The ABLE intervention aims to reduce sedentary behavior using activity monitoring, activity scheduling, problem-solving, and self-assessment to promote engagement in meaningful daily activities. The purpose of this study was to assess the feasibility (tolerability, acceptability, reliability, safety) of the ABLE intervention after stroke and describe trends in sedentary behavior at baseline and 4 weeks.

Clinical Presentation: Participants (n = 5) who were 6 months to 2 years post-stroke, ambulatory, and reported ≥6 h of daily sitting time.

Intervention: Twelve ABLE intervention sessions (3x/week for 4 weeks) conducted in participants’ homes. The ABLE intervention includes activity monitoring, activity scheduling, self-assessment, and collaborative problem-solving.

Results: All feasibility benchmarks were met for three participants. Two participants met tolerability and safety benchmarks but did not meet acceptability and reliability benchmarks. Variability in feasibility and sedentary behavior outcomes may be related to baseline levels of sedentary behavior and social support.

Conclusions: The ABLE intervention was tolerable and safe. The intervention protocol was refined to enhance reliability and acceptability. Future studies should estimate the effects of the ABLE intervention.