Monte Carlo calculation of dose rate distributions around the Walstam CDC.K-type 137Cs sources

Basic dosimetric data for the Walstam CDC.K-type low dose rate 137Cs sources in water have been calculated using Monte Carlo techniques. These sources, CDC.K1 -K3 and CDC.K4, are widely used in a range of applicators and moulds for the treatment of intracavitary and superficial cancers. Our purpose is to improve existing data about these sources using the Monte Carlo simulation code GEANT3. Absolute dose rate distributions in water have been calculated around these sources and are presented as conventional 2D Cartesian look-up tables. Also the AAPM Task Group 43 formalism for dose calculation has been applied. The calculated dose rate constant for the CDC.K1-K3 source is A = 1.106 +/- 0.001 cGy h(-1) U(-1), and for the CDC.K4 source, A = 1.092 +/- 0.001 cGy h(-1) U(-1). The anisotropy of the sources are accurately studied and F(r, theta) tables are given. Also phi an(r) factors are presented. The radial dose functions are given as a polynomial fit to the calculated data up to 15 cm. Best-fit values of coefficients suitable for use in Sievert integral calculations have been derived.     

Continuous renal replacement therapy outcomes in acute kidney injury and end-stage renal disease: a cohort study

Introduction

Continuous renal replacement therapy (CRRT) is a widely used but resource-intensive treatment. Despite its broad adoption in intensive care units (ICUs), it remains challenging to identify patients who would be most likely to achieve positive outcomes with this therapy and to provide realistic prognostic information to patients and families.

Methods

We analyzed a prospective cohort of all 863 ICU patients initiated on CRRT at an academic medical center from 2008 to 2011 with either new-onset acute kidney injury (AKI) or pre-admission end-stage renal disease (ESRD). We examined in-hospital and post-discharge mortality (for all patients), as well as renal recovery (for AKI patients). We identified prognostic factors for both in-hospital and post-discharge mortality separately in patients with AKI or ESRD.

Results

In-hospital mortality was 61% for AKI and 54% for ESRD. In patients with AKI (n = 725), independent risk factors for mortality included age over 60 (OR 1.9, 95% CI 1.3, 2.7), serum lactate over 4 mmol/L (OR 2.2, 95% CI 1.5, 3.1), serum creatinine over 3 mg/dL at time of CRRT initiation (OR 0.63, 95% CI 0.43, 0.92) and comorbid liver disease (OR 1.75, 95% CI 1.1, 2.9). Among patients with ESRD (n = 138), liver disease was associated with increased mortality (OR 3.4, 95% CI 1.1, 11.1) as was admission to a medical (vs surgical) ICU (OR 2.2, 95% CI 1.1, 4.7). Following discharge, advanced age became a predictor of mortality in both groups (AKI: HR 1.9, 95% CI 1.2, 3.0; ESRD: HR 4.1, 95% CI 1.5, 10.9). At the end of the study period, only 25% (n = 183) of patients with AKI achieved dialysis-free survival.

Conclusions

Among patients initiating CRRT, risk factors for mortality differ between patients with underlying ESRD or newly acquired AKI. Long-term dialysis-free survival in AKI is low. Providers should consider these factors when assessing prognosis or appropriateness of CRRT.     

Promising results of the chaperone effect caused by iminosugars and aminocyclitol derivatives on mutant glucocerebrosidases causing Gaucher disease

Gaucher disease is an autosomal recessive disorder. It is characterized by the accumulation of glucosylceramide in lysosomes of mononuclear phagocyte system, attributable to acid β-glucosidase deficiency. The main consequences of this disease are hepatosplenomegaly, skeletal lesions and, sometimes, neurological manifestations. At sub-inhibitory concentrations, several competitive inhibitors act as chemical chaperones by inducing protein stabilization and increasing enzymatic activity. Here we tested two iminosugars (NB-DNJ and NN-DNJ) and four aminocyclitols with distinct degrees of lipophilicity as pharmacological chaperones for glucocerebrosidase (GBA). We report an increase in the activity of GBA using NN-DNJ, NB-DNJ and aminocyclitol 1 in stably transfected cell lines, and an increment with NN-DNJ and aminocyclitol 4 in patient fibroblasts. These results on specific mutations validate the use of chemical chaperones as a therapeutic approach for Gaucher disease. However, the development and analysis of new compounds is required in order to find more effective therapeutic agents that are active on a broader range of mutations.     

Suppression of ongoing experimental allergic encephalomyelitis in DA rats by novel peptide drug,structural part of human myelin basic protein 46–62

Previously, we demonstrated that autoantibodies (AAb) in multiple sclerosis (MS) reveal site-specific binding and cleavage toward myelin basic protein (MBP) epitope library. We have found several fragments of MBP immunodominant in terms of AAb binding. Here, we applied these peptides to DA rats with induced protracted relapsing experimental allergic encephalomyelitis (EAE) most closely related to MS. DA rats with EAE induced by syngenic spinal cord homogenate in complete Freund's adjuvant were treated by nasal route with human MBP 46–62, 81–102, 124–139, 147–170, and Copaxone®. MBP 124–139 and 147–170 displayed only mild therapeutic effects but MBP 46–62 significantly reduced EAE, reflected by lower clinical scores and shorter EAE duration compared to controls.     

藻酸钠复合自体软骨细胞修复猪关节软骨缺损的近期效果

目的:采用藻酸钠自体软骨细胞混合物修复猪的关节软骨缺损,观察近期成骨效应。方法:实验于2004-03/2005-04在中山大学附属第二医院实验中心完成。3个月龄的小型猪8只,取其关节软骨进行细胞原代培养,获取原代细胞后,分别进行免疫组织化学法检测细胞Ⅱ型胶原表达。然后对8只小型猪的32个关节进行动物关节缺损的模型建立,每个关节共造3个人工缺损,选择关节左右随机对照。将已经培养好的软骨细胞与已经配制好并消毒的藻酸钠混合,移植到猪的关节软骨缺损处。每只猪关节内注射3个实验点,1个用藻酸钠/细胞混合液为实验组,1个单纯支架材料为单纯材料对照组,1个缺损做空白对照组,模型中缺损区均为关节负重区,胶原纤维绿色(亮绿复染)。修复所用细胞为自体软骨体外培养后,进行移植修复,采用3代体外培养软骨细胞,均匀混和藻酸钠后,行自体移植。8周后取实验关节进行大体观察、苏木精-伊红染色、Masson染色、免疫组织化学法染色观察及O’driscoll组织学评分。结果:纳入小型猪8只,除其中1例因手术切断伸直肌腱而使猪关节活动障碍,其余均未见手术后关节活动障碍,所有手术无术后感染,无关节内感染,无动物死亡。移植的软骨细胞在藻酸钠载体中生长良好,形成透明软骨。根据O’driscoll组织学评分标准,实验组32个猪关节缺损修复的组织学评分为(20.25±1.64)分,高于单纯材料对照组的(7.46±1.29)分及空白对照组的(6.00±2.09)分。免疫组织化学染色可见修复软骨以表达Ⅱ型胶原为主,无Ⅰ型胶原。结论:藻酸钠复合自体软骨细胞作为软骨移植的替代物是可行的,远期效果还有待进一步研究。     

Relaxation and cGMP formation in response to sildenafil and sodium nitroprusside in saphenous veins from normotensive and hypertensive patients

BACKGROUND: This study was designed to measure cyclic guanosine 3'5' monophosphate (cGMP) formation and relaxation response to sildenafil given either alone or in combination with sodium nitroprusside in saphenous veins obtained from normotensive and hypertensive patients. METHODS: Saphenous vein rings were obtained from 13 hypertensive and nine normotensive patients undergoing coronary artery bypass surgery. The vein rings were suspended in organ bath chambers for isometric recording of tension. The effect of sildenafil on sodium nitroprusside-induced cGMP formation was also assessed. RESULTS: Sildenafil (10 nmol/L to 100 micromol/L) and sodium nitroprusside (0.01 to 100 nmol/L) caused concentration-dependent relaxations that were of greater magnitude in veins from normotensive patients. Sildenafil (1 to 10 micromol/L) amplified the relaxation induced by sodium nitroprusside in both groups of veins, but this effect was more pronounced in veins from hypertensive patients. Levels of cGMP in response to sodium nitroprusside were significantly lower in veins from hypertensive subjects. However, in the presence of sildenafil, the increase in cGMP levels in response to sodium nitroprusside was significantly greater in the hypertensive as compared with the normotensive group. CONCLUSIONS: Although the relaxant effects of sildenafil are less pronounced in veins from hypertensive patients, the synergistic interaction sildenafil-sodium nitroprusside is more effective in veins from hypertensive patients, mainly due to an increase in cGMP accumulation.     

MOLECULAR IDENTIFICATION OF Bartonella henselae IN A SERONEGATIVE CAT SCRATCH DISEASE PATIENT WITH AIDS IN RIO DE JANEIRO, BRAZIL

Bartonella henselae is associated with a wide spectrum of clinical manifestations, including cat scratch disease, endocarditis and meningoencephalitis, in immunocompetent and immunocompromised patients. We report the first molecularly confirmed case of B. henselae infection in an AIDS patient in state of Rio de Janeiro, Brazil. Although DNA sequence of B. henselae has been detected by polymerase chain reaction in a lymph node biopsy, acute and convalescent sera were nonreactive.     

Inhibition and reversal of platelet-rich arterial thrombus in vivo: direct vs. indirect factor Xa inhibition

BACKGROUND/OBJECTIVE: The efficacy of a direct factor (F)Xa inhibitor, ZK-807834, was compared with indirect inhibition by enoxaparin for inhibition and deaggregation of acute platelet-rich thrombi in a well-characterized porcine carotid injury model. METHODS: A crush injury was performed on a randomly chosen carotid artery and the thrombus allowed to propagate for 30 min. Pigs then received intravenous drug for 35 min: ZK-807834-Dose 1 (40 microg kg(-1) bolus + 1.5 microg kg(-1) min(-1) infusion, n=6); ZK-807834-Dose 2 (20 microg kg(-1) bolus + 0.75 microg kg(-1) min(-1) infusion; n=6); enoxaparin (1 mg kg(-1) bolus; n=6); or saline (n=6). Five minutes after drug initiation, the contralateral artery was injured. Thrombus size was monitored by scintillation detection of autologous 111In-platelets. RESULTS: The prothrombin time ratio was 2.2 +/- 0.1; 1.4 +/- 0.3; 1.2 +/- 0.9 and 1.1 +/- 0.2, respectively. ZK-807834-Dose 1 significantly inhibited carotid platelet deposition (525 +/- 226 x 10(6) cm(-2); P = 0.008), whereas ZK-807834-Dose 2 (2325 +/- 768) and enoxaparin (1236 +/- 383) were not different from saline (2776 +/- 642). Thrombus deaggregation was greatest for animals receiving ZK-807834-Dose 1 (473 +/- 185). Neither ZK-807834-Dose 2 (1588 +/- 480) nor enoxaparin (1618 +/- 686) was different from saline control (2222 +/- 598). CONCLUSIONS: Direct FXa inhibition with ZK-807834, at a prothrombin time ratio of 2.2, effectively inhibits thrombosis and promptly deaggregates thrombi induced by arterial injury. In contrast, indirect FXa inhibition with enoxaparin was ineffective.     

The necessary and the unnecessary transfusion: a critical review of reported appropriateness rates and criteria for red cell transfusions

BACKGROUND: The purpose of this study was to evaluate the criteria for assessing the appropriateness of red cell transfusions. The data were obtained by a computer search of all English-language literature from 1966 to October 1992. STUDY DESIGN AND METHODS: Nine studies were selected, which dated from 1986 to 1989 and employed explicit criteria evaluating the appropriateness of red cell transfusion in adults. The following data were abstracted from all studies: study design, timing, location, criteria for evaluating appropriateness, and rate of appropriate or inappropriate transfusions. RESULTS: Five studies evaluated transfusion appropriateness. Appropriateness rates ranged from 88 to 99 percent in three studies, and inappropriateness rates ranged from 0.3 to 57.3 percent in two studies. Four studies evaluated transfusion inappropriateness and reported inappropriateness rates of 18 to 55 percent. Substantial variation was found in the criteria for an appropriate or an inappropriate transfusion. Appropriateness rates did not depend upon characteristics of the study design, location, or timing of data collection. Restrictiveness in the criteria used to determine appropriateness and the use of additional implicit evaluation after an initial explicit review affected appropriateness rates. CONCLUSION: In the 1980s, high rates of inappropriate transfusion and low rates of appropriate transfusion were still reported. Appropriateness rates varied widely, in part because of marked variation in the criteria for an appropriate transfusion. Newly derived standards for an appropriate red cell transfusion, published in 1992, appear to provide a simple and objective means of evaluating the appropriateness of a transfusion. Appropriateness rates resulting from the application of these new standards have not yet been determined.     

有氧运动延缓衰老线粒体DNA突变的机制

目的:线粒体DNA突变在衰老过程中起核心作用。总结有氧运动在延缓机体衰老过程中对线粒体DNA突变的影响,探讨有氧运动延缓衰老的机制。资料来源:应用计算机检索Medline数据库1996-01/2006-01期间关于线粒体DNA突变与有氧运动延缓衰老的文章,检索词为"aerobics exercise,aging,mtDNA mutation",限定文章语言种类为English。同时计算机检索中国期刊全文数据库、万方数据库1994-01/2006-12期间的有氧运动、衰老和线粒体DNA突变相关的文章,检索词"衰老,线粒体DNA突变,有氧运动",并限定文章语言种类为中文。资料选择:对资料进行初审,纳入标准:①有氧运动延缓衰老关系的理论研究。②线粒体DNA突变与衰老关系的基础与临床研究。③有氧运动对线粒体DNA突变的影响研究。资料提炼:共收集到36篇线粒体DNA突变与有氧运动延缓衰老相关的文献,均为全文,32篇符合纳入标准,排除4篇重复性研究。资料综合:①有氧运动可以通过减少线粒体DNA突变,从而达到延缓机体的衰老。有氧运动可能通过影响自由基及抗氧化系统、细胞凋亡、线粒体的结构和功能,对衰老进程产生重要影响。②线粒体DNA突变随增龄而积累,达到一定阈值后,可导致细胞能量供应的严重障碍,从而造成组织器官生理功能的减退。③长期有氧运动可通过刺激心肌、骨骼肌线粒体的生成及蛋白质的合成而延缓线粒体形态结构的改变,有利于维持线粒体功能以满足机体对其能源的需求。结论:中、低强度有氧运动可以提高机体有氧工作能力,增进线粒体氧化磷酸化的功能,对延缓衰老具有一定的积极作用。有氧运动可以减少心肌、骨骼肌等线粒体DNA突变,提示有氧运动在延缓衰老机制中,减少线粒体DNA突变是可能机制之一。