大剂量甲氨蝶呤治疗儿童ALL的血药浓度监测及其临床意义

目的分析儿童急性淋巴细胞白血病（ALL）采用大剂量甲氨蝶呤（MTX）化疗时的血药浓度监测结果,探讨其对于甲酰四氢叶酸钙（CF）个体化解救的临床意义。方法140例ALL患儿按照ALL危险度分组,标危组接受3．0g·m^-2 MTX治疗,高危组接受5．0g·m^-2 MTX治疗。采用高效液相色谱法测定MTX给药后固定时间点（24、44、68h）的血药浓度,根据血药浓度结果调整CF解救方案,同时观察不良反应。结果标危组24、44、68hMTX血药浓度分别为29．80±15．07、0．47±0．41、0．09±0．07μmol·L^-1,高危组24、44、68hMTX血药浓度分别为57．17±16．65、1．22±1．86、0．53±0．54μmol·L^-1,MTX血药浓度有显著的个体差异;不同剂量组CF解救剂量有显著差异;高危组中MTX排泄延迟的发生率较高（28／99）;所有病例无不可逆的严重不良反应发生。结论大剂量MTX化疗时的血药浓度监测是非常必要的,对于CF解救的个体化具有十分重要的临床意义。     

小儿急性淋巴细胞白血病HD—MTX—CF治疗方案的血药浓度监测分析

目的:通过对大剂量甲氨蝶呤(HD-MTX)治疗小儿急性淋巴细胞白血病血药浓度的分析,探讨甲氨堞呤血药浓度监测的临床意义.方法:采用荧光偏振免疫法(FPIA)监测接受大剂量甲氨蝶呤化疗的32例急性淋巴细胞白血病患儿血药浓度.结果:在应用HD-MTX开始后72 h、90 h时MTX血药浓度的变异系数分别为211.76%、128.57%;应用后72 h血药浓度大于1 μmol/L有4例;应用后90 h血药浓度大于0.1 μmol/L 2例且惠儿出现了口腔粘膜溃疡.所有患儿无不可逆的严重不良反应.结论:患儿应用MTX后血药浓度个体差异较大,通过血药浓度监测可以调整甲酰四氢叶酸钙(CF)的解救时间和剂量,有效防止严重不良反应的发生,保证化疗的有效性和安全性. FPIA)监测接受大剂量甲氨蝶呤化疗的32例急性淋巴细胞白血病患儿血药浓度.结果:在应用HD-MTX开始后72 h、90 h时MTX血药浓度的变异系数分别为211.76%、128.57%;应用后72 h血药浓度大于1 μmol/L有4例;应用后90 h血药浓度大于0.1 μmol/L 2例且惠儿出现了口腔粘膜溃疡.所有患儿无不可逆的严重不良反应.结论:患儿应用MT 后血药浓度个体差异较大,通过血药浓度监测可以调整甲酰四氢叶酸钙(CF)的解救时间和剂量,有效防     

儿童急性淋巴细胞白血病化疗中甲氨蝶呤血药浓度监测结果分析

目的评价儿童急性淋巴细胞白血病(ALL)化疗中甲氨蝶呤(MTX)消除的个体差异性,为临床制订合理的解救治疗方案提供依据。方法 81例ALL患儿行大剂量甲氨蝶呤(HDMTX)化疗339次,MTX剂量为3～5 g.m-2,24 h持续静脉滴注。用固相萃取高效液相色谱法测定用药后24,48,72 h血清中MTX浓度。统计各时间点浓度值,并计算变异系数(CV)。用Spearman相关分析考察48,72 h MTX血药浓度的相关性。结果 48,72 h MTX血药浓度变异系数较大,血药浓度呈正相关。结论 MTX在ALL患儿体内的消除情况存在极大的个体差异性,有必要通过血药浓度监测来指导亚叶酸钙(CF)的解救次数和剂量。     

大剂量甲氨蝶呤治疗儿童急性淋巴细胞白血病耐受性临床研究

目的:观察大剂量甲氨蝶呤(MTX)连续24 h持续静脉输注治疗儿童急性淋巴细胞白血病的临床耐受性。方法:72例次急性淋巴细胞白血病患儿进行大剂量甲氨蝶呤连续24 h持续静脉输注,第36 h亚叶酸钙解救,检测36 h4、8 h、72 h MTX血药浓度,观察不良反应发生率。结果:不良反应表现为消化道症状、肝功能损害和Ⅰ°~Ⅱ°白细胞减少、Ⅰ°~Ⅱ°口腔粘膜损害,无严重不良反应发生。92.5%的患儿72 h MTX血药浓度<0.1μmol/L。结论:大剂量MTX加亚叶酸钙解救治疗儿童急性淋巴细胞白血病,耐受性较好。个别患儿出现排泄延迟,通过监测MTX血药浓度,增加亚叶酸钙解救次数,可防止严重不良反应发生。     

大剂量甲氨蝶呤在急性淋巴细胞白血病患儿体内的药动学研究

目的研究急性淋巴细胞白血病(ALL)患儿接受大剂量甲氨蝶呤(HDMTX)静脉滴注联合甲酰四氢叶酸钙解救方案治疗时甲氨蝶呤的药动学。方法采用高效液相色谱法测定16例ALL患儿使用甲氨蝶呤后不同时间点血清药物浓度,所得血药浓度-时间数据经DAS软件拟合,优化药动学房室模型,计算其药动学参数。结果大剂量甲氨蝶呤在急性淋巴细胞白血病患儿体内的经时过程符合二房室模型,主要药动学参数分别为:t1/2α=(1.61±0.43)h,t1/2β=(11.05±3.54)h,V1=(18.552±5.902)L·m-2,Cl=(4.525±1.181)L.h-1.m-2,k10=(0.254±0.053)h-1,k12=(0.194±0.043)h-1,k21=(0.074±0.025)h-1,AUC(0-t)=(1064.0±258.6)μmol.h.L-1,AUC(0-∞)=(1433.6±485.2)μmol·h·L-1,tmax=24h,Cmax=(40.1±10.3)μmol·L-1。结论大剂量甲氨蝶呤在急性淋巴细胞白血病患儿体内的药动学符合二房室模型,主要药动学参数有较明显的个体差异。     

儿童急性淋巴细胞白血病甲氨蝶呤化疗方案优化的研究

目的:监测急性淋巴细胞白血病(ALL)儿童血清中甲氨蝶呤(MTX)浓度,比较2种大剂量甲氨蝶呤(HD-MTX)用药方案抗白血病作用及毒性作用,评价固相萃取高效液相色谱法(Spe-HPLC)指导儿童ALL化疗的价值.方法:ALL患儿44例,男24例,女20例,分为24 h持续静脉滴注组(24 h组)和12 h持续静脉滴注组(12 h组),MTX剂量3～5 g·m-2静脉滴注,Spe-HPLC测定用药后血药浓度,接WHO化疗药物毒性标准评价其毒性作用,比较2组患儿之间第24小时达到胞外所需抗白血痛MTX浓度的比率、不良反应、解救药物四氢叶酸钙(CF)使用次数、住院时间及治疗费用的差异.结果:24 h组第24小时达到胞外所需MTX浓度的比率显著高于12 h组;2组之间毒性作用差异无显著性;CF使用次数、患儿住院时间及治疗费用并不显著增加.结论:甲氨蝶呤血药浓度监测,指导H13-MTX化疗方案改进,24 h持续静脉滴注用药方案显著增强MTX的抗白血病作用,提高白血病治疗远期疗效,但不显著增加MTX的不良反应,具有重要临床价值.     

MTHFR基因多态性与ALL患儿MTX血药浓度及严重毒副反应的相关性研究

目的:在儿童急性淋巴细胞白血病(ALL)患者中,探讨亚甲基四氢叶酸还原酶(MTHFR C677T和A1298C)基因多态性与甲氨蝶呤(MTX)化疗后44 h血药浓度和严重毒副反应间的相关性.方法:收集77例ALL患儿临床资料,监测MTX输注后44 h的血药浓度并进行MTHFR基因分型;分析MTHFR C677T基因型和...     

甲氨蝶呤的血药浓度对亚叶酸钙用药方案的指导作用

目的:探讨甲氨蝶呤血药浓度监测对亚叶 酸钙应用方案的指导作用。方法:11例急性淋巴细 胞性白血病(ALL)病儿,予20例次大剂量甲氨蝶呤 (每次3g·m-2)治疗。以常规剂量亚叶酸钙援救 每次12～15mg·m-2,q6h,共8次。于用药后24 36,48,72h用高效液相色谱法测定血药浓度。结 果:9例病儿达到完全缓解;2例病儿出现严重的不 良反应抢救无效死亡。结论:应参考甲氨蝶呤血药 浓度,进行适当的亚叶酸钙援救,以防止出现严重的 不良反应。     

大剂量甲氨蝶呤在儿童急性淋巴细胞白血病治疗中血药浓度监测的临床研究

目的:观察大剂量甲氨蝶呤化疗在儿童急性淋巴细胞白血病治疗中的应用,了解其不良反应及血药浓度监测的意义.方法:急性淋巴细胞白血病标危患儿120例应用大剂量甲氨蝶呤治疗,观察并总结其不良反应发生的种类及相应血药浓度结果.结果:胃肠道反应、肝功能损害、口腔溃疡是大剂量甲氨蝶呤常见的不良反应.48 h血清浓度>0.25umol/L不良反应发生率较高.结论:监测甲氨蝶呤血清浓度,充分水化、碱化,适当给予甲酰四氢叶酸钙解救,是保证大剂量使用甲氨蝶呤临床安全的关键因素.     

大剂量甲氨蝶呤在儿童急性淋巴细胞白血病治疗中的副作用

目的观察大剂量甲氨蝶呤（Methothexate,MTX）治疗儿童急性淋巴细胞白血病的副作用。方法对10例47例次急性淋巴细胞白血病（acute lymphobalstic leukemia,ALL）患儿进行大剂量甲氨蝶呤连续24h持续静脉滴注,第42h四氢叶酸钙（FH4）解救,检测44h MTX血药浓度,观察副作用发生率。结果副作用主要为肝功能损害。口腔黏膜糜烂、肛周糜烂、消化道症状,1例引起严重的剥脱性皮炎。结论大部分患儿对于大剂量MTX的副反应可耐受,极少数会引起严重的不良反应。     

颅脑损伤患者并发肺部感染的护理体会

目的：为了使并发肺部感染的病人更多、更好、更早的痊愈。方法：通过对32例颅脑外伤并发肺部感染病人的严密观察,采取更换体位、超声雾化、有效排痰训练等有效的护理措施干预,从而控制了肺部感染。结果：痊愈17例,占53.1%;显效12例,占37.5%,无效2例,占6.2%;死亡1例,占3.1%;实践证明,有效的护理干预对提高患者治疗成功率有着重要意义。     

卡马西平联用尼美舒利相关粒细胞缺乏症

1例78岁男性患者因带状疱疹神经痛、慢性阻塞性肺疾病合并感染,给予头孢唑肟钠（2.25 g静脉滴注,1次/d）、卡马西平（0.2 g口服,2次/d）、尼美舒利（100 mg口服,2次/d）、二羟丙茶碱（0.5 g静脉滴注,1次/d）、甲钴胺（0.5 mg口服,3次/d）、地塞米松（5 mg,静脉滴注1次）、盐酸哌替啶（25 mg,肌内注射1次）和盐酸布桂嗪（100 mg,肌内注射3次）等药物治疗。第7天,停用头孢唑肟钠,改为磷霉素钠（8 g静脉滴注,1次/d）。第11天,血常规检查示白细胞计数1.6×10^9/L,中性粒细胞0.03,中性粒细胞绝对值0.1×10^9/L,淋巴细胞绝对值0.9×10^9/L。立即停用所有药物,给予对症支持治疗。第15天,外周血白细胞计数0.9×10^9/L,中性粒细胞0.02,中性粒细胞绝对值0.1×10^9/L,淋巴细胞绝对值0.7×10^9/L。行骨髓穿刺检查,诊断为粒细胞缺乏症。第17天患者出现右肺气胸、肺不张。第20天出现急性呼吸衰竭、多脏器衰竭合并重症感染,经抢救无效死亡。     

Satisfaction with information and its relationship with adherence in patients with chronic pain

□ Due to the nature of chronic pain it would be expected that patients are highly adherent to their pain medication. However, results from this study have shown that 23 per cent of patients often or always avoid using their pain medication, 13.4 per cent often or always alter dosages, and 10.3 per cent often or always stop taking their medication for a while. This suggests intentional non‐adherence to pain medication □ Less than 50 per cent of respondents were satisfied with information provided on side effects, what to do if side effects occur, and possible interactions with other medication □ Patients' satisfaction with information about their medication was related to self‐reported adherence; greater satisfaction was associated with higher self‐reported adherence     

Genomic profiling associated with recurrence in patients with rectal cancer treated with chemoradiation

PURPOSE: Stage II and III adenocarcinoma of the rectum has an overall 5-year survival rate of approximately 50%, and tumor recurrence remains a major problem despite an improvement in local control through chemotherapy and radiation. The efficacy of chemoradiation therapy may be significantly compromised as a result of interindividual variations in clinical response and host toxicity. Therefore, it is imperative to identify those patients who will benefit from chemoradiation therapy and those who will develop recurrent disease. In this study, we tested whether a specific pattern of 21 polymorphisms in 18 genes involved in the critical pathways of cancer progression (i.e., drug metabolism, tumor microenvironment, cell cycle regulation, and DNA repair) will predict the risk of tumor recurrence in rectal cancer patients treated with chemoradiation. PATIENTS AND METHODS: A total of 90 patients with Stage II or III rectal cancer treated with chemoradiation were genotyped using polymerase chain reaction (PCR)-based techniques for 21 polymorphisms. RESULTS: A polymorphism in interleukin (IL)-8 was individually associated with risk of recurrence. Classification and regression tree analysis of all polymorphisms and clinical variables developed a risk tree including the following variables: node status, IL-8, intracellular adhesion molecule-1, transforming growth factor-beta, and fibroblast growth factor receptor 4. CONCLUSION: Genomic profiling may help to identify patients who are at high risk for developing tumor recurrence, and those who are more likely to benefit from chemoradiation therapy. A larger prospective study is needed to validate these preliminary data using germline polymorphisms on tumor recurrences in rectal cancer patients treated with chemoradiation.     

甘草酸单铵结合氦-氖激光治疗银屑病62例

目的用甘草酸单铵结合低能量氦-氖激光,观察治疗银屑病患者。方法62例寻常型银屑病患者,分为两组,A组用低能量氦-氖激光血管内照射,同时用甘草酸单铵静脉滴注,共36例;B组仅用甘草酸单铵,共26例。通过30d治疗。结果总有效率82.2%,其中A组有效率88.9%,B组73.1%(经Ridit检验,U＝2.76,P＜0.01),两组差异有极显著性意义。结论甘草酸单铵结合氦-氖激光治疗银屑病,比单用甘草酸单铵效果好。     

A fetus with meckel-gruber syndrome associated with isomerism

Abstract. Meckel-Gruber syndrome (MKS) is an autosomal recessive lethal malformation. As far as we know, the rate of incidence for the syndrome is 0.02 per 10,000 births. It is estimated that Meckel-Gruber syndrome accounts for 5% of all neural tube defects in Finland. Objective. The aim of this study is to present a case of a fetus with Meckel-Gruber syndrome associated with complete left isomerism. Method. The fetus was obtained after medical interruption of the pregnancy during the fifteenth gestational week. The mother was 36 years old and in a consanguineous marriage. The antenatal ultrasound examination revealed a polymalformative syndrome, leading to a postmortem examination. The fetopathological study of the fetus was conducted at the Centre for Maternity and Neonatology, Tunis, Tunisia, in 2008. Results. The female fetus had a significantly deformed ballooning abdomen, pes equinovarus, flexion of the wrist and a total posterior cleft palate. The central nervous system abnormalities were occipital encephalocele, cystic dilatation of the fourth ventricle, agenesis of corpus callosum and hydrocephalus. The study of the internal organs found dextrocardia, irregular lobulation of the lungs, left isomerism, and polysplenia. The microscopic examination revealed bilateral cystic dilation of the kidneys, fibrous proliferation of the liver and ectasic dilatation of the billiary ducts, representing a ductal plate malformation of the liver. Conclusion. The case is diagnosed with Meckel-Gruber syndrome associated with complete left isomerism, cleft palate and possibly Dandy-Walker syndrome.