脉搏连续心排血量指导重症急性胰腺炎早期液体复苏的效果评价

目的:探讨脉搏连续心排血量(Pi CCO)指导早期应用液体复苏对重症急性胰腺炎(SAP)的临床意义。方法:应用Pi CCO指导早期液体复苏的37例SAP患者作为Pi CCO组,选择同期应用中心静脉压(CVP)指导液体复苏的39例SAP患者作为对照组,比较2组48 h内液体出入量、血管活性药物使用时间以及机械通气时间、ICU住院时间和28 d病死率。并应用受试者工作特征性(ROC)曲线分析28 d病死率的危险因素。结果:2组年龄、性别、入院血糖、血乳酸、血肌酐、氧和指数、平均动脉压、APACHEⅡ评分均无显著差异(P0.05)。Pi CCO组患者0~6 h补液量明显多于对照组,而0~72 h补液量较对照组明显减少(均P0.05)。Pi CCO组患者的血液净化率、机械通气时间、ICU住院时间均显著减少(P0.05),但2组患者应用血管活性药物的比例、导管相关感染率和28 d病死率均无显著差别(P0.05)。ROC曲线发现年龄(AUC 0.71,95%CI,0.63~0.76,P=0.03)和APACHEⅡ评分(AUC0.78,95%CI,0.67~0.91,P=0.02)为预测28 d病死率的重要因素。结论:Pi CCO可以精确指导SAP患者早期液体复苏,并减少机械通气时间和ICU住院时间。     

脉搏指示连续心搏出量检测技术对严重肺部感染合并心力衰竭患者预后的影响和危险因素分析

目的 探讨脉搏指示连续心搏出量检测（PiCCO）指导液体管理对重症肺炎合并心衰竭的预后意义,并分析影响短期病死率的危险因素。方法 选择北京大学首钢医院重症监护室（ICU）自2013年1月～2015年1月收治并应用PiCCO技术指导液体管理的57例重症肺炎合并心力衰竭的患者作为PiCCO组,同期选择基础情况类似的应用中心静脉压（CVP）指导液体管理的64例重症肺炎合并心衰患者作为对照组,比较两组72h内液体管理数据,治疗1d和3d的APACHE II评分、SOFA评分、CPIS评分变化,以及住院期间血管活性药物使用时间、机械通气时间、床旁血液净化率、ICU住院时间和28天病死率。Kaplan-Meier生存分析评价两组的生存情况。Logistic回归分析28天病死率的危险因素。并应用受试者工作特征性（ROC）曲线分析危险因素的阈值和相应的敏感性和特异性。结果 共有121例患者入选,男73例,女48例,平均年龄62.3±17.2岁。两组间年龄、性别比例、既往病史、血乳酸、血肌酐、氧合指数、平均动脉压、APACHE II 评分、SOFA评分、CPIS评分等均无显著差异（均P>0.05）。PiCCO组患者的0～12h液体出量明显多于对照组（P<0.05）,但24～48h、48～72h两组无显著差别（P>0.05）。治疗3d时,PiCCO组患者的APACHE II、 SOFA评分均较对照组显著降低,但CPIS评分两组无明显差异。住院期间PiCCO组的应用血管活性药物的比例、血液净化率、机械通气时间、ICU住院时间较对照组均显著减少（P<0.05）,但Kaplan-Meier生存分析显示两组住院期间和28天生存均无显著差别（P>0.05）。Logistic回归分析显示年龄（OR 1.71, 95% CI, 1.13～2.73,P=0.003）、APACHE II评分（OR 1.92, 95% CI, 1.17～3.72,P=0.01）、SOFA评分（OR 2.32, 95% CI, 1.87～4.52,P=0.02）和机械通气时间（OR 2.08, 95% CI, 1.47～3.93,P=0.002）为28天病死率的独立危险因素,ROC曲线显示年龄≥67岁、SOFA ≥6分、APACHE II≥23分和机械通气时间≥7天为相应危险因素的阈值。结论 PiCCO技术可以精确指导重症肺炎合并心力衰竭患者液体管理,降低APACHE II、 SOFA评分,减少机械通气时间和ICU住院时间,但对短期病死率无明显影响。年龄、APACHE II评分、SOFA评分和机械通气时间为28天病死率的独立危险因素。     

脉搏指示连续心搏出量检测技术对严重肺部感染合并心力衰竭患者预后的影响

目的:探讨脉搏指示连续心搏出量检测(PiCCO)技术指导液体管理对重症肺炎合并心力衰竭预后的影响。方法:选择重症肺炎合并心力衰竭患者121例,应用PiCCO技术指导液体管理的57例患者作为PiCCO组,同期选择基础情况类似的应用中心静脉压指导液体管理的64例患者作为对照组,比较2组临床资料和预后情况。结果:PiCCO组患者的0~12 h液体出量明显多于对照组(P0.05),但24~48 h、48~72 h 2组无显著差别(P0.05)。治疗3d时,PiCCO组患者的APACHEⅡ、SOFA评分均较对照组显著降低,但CPIS评分2组无明显差异。住院期间Pi CCO组应用血管活性药物的比例、血液净化率、机械通气时间等较对照组均显著减少(均P0.05),但2组住院期间和28d生存均无显著差别(P0.05)。Logistic回归分析显示年龄(P=0.003)、APACHEⅡ评分(P=0.01)、SOFA评分(P=0.02)和机械通气时间(P=0.002)为28 d病死率的独立危险因素,年龄≥67岁、SOFA≥6分、APACHEⅡ≥23分和机械通气时间≥7 d为相应危险因素的阈值。结论:PiCCO技术可以精确指导重症肺炎合并心力衰竭患者液体管理,减少机械通气时间和ICU住院时间,但对短期病死率无明显影响。年龄、APACHEⅡ评分、SOFA评分和机械通气时间为28 d病死率的独立危险因素。     

重症超声联合中心静脉血氧饱和度可指导脓毒症休克患者液体复苏治疗

目的：探讨重症超声联合中心静脉血氧饱和度（ScvO2）对脓毒症休克患者容量复苏的效果评价。方法：选取脓毒症休克患者86例，随机分为观察组（43例）和对照组（43例）。对照组采用ScvO2指导容量复苏，观察组采用重症超声联合ScvO2指导容量复苏。观察2组患者复苏前、复苏6h心率（HR）、平均动脉压（MAP）、中心静脉压（CVP）、血乳酸（LAC）、急性生理和慢性健康状况评估（APACHEⅡ）评分及液体复苏量、机械通气时间、重症监护病房（ICU）住院时间、6h复苏达标率、28d死亡率。结果：复苏6h时，观察组患者血LAC水平显著低于对照组（P＜0.05）。与复苏前比较，复苏6h时对照组患者MAP、CVP水平显著升高，LAC水平显著降低（P均＜0.05）；观察组患者MAP、CVP水平显著升高，HR、LAC水平显著降低（P均＜0.05）。观察组患者复苏液体量、机械通气时间、ICU住院时间显著低于对照组，6h复苏达标率显著高于对照组（P均＜0.05）；2组患者28d死亡率比较，差异无统计学意义（P＞0.05）。结论：重症超声联合ScvO2指导脓毒症休克患者容量复苏可降低复苏6h血LAC水平及复苏液体量，缩短机械通气及ICU住院时间，提高复苏效果。     

DCRRT治疗重症急性胰腺炎并急性肺损伤的临床观察

目的探讨日间连续性肾替代疗法（DCRRT）治疗重症急性胰腺炎（SAP）并急性肺损伤（ALI）的临床疗效。方法将40例SAP并ALI患者随机分为DCRRT组、对照组各20例,检测两组治疗前后血浆TNF-α、IL-6、IL-8,比较其生命体征、氧合指数、急性生理与慢性健康评估评分（APACHEⅡ评分）、机械通气时间、ICU住院时间及病死率。结果与对照组比较,DCRRT组TNF-α、IL-6、IL-8下降,生命体征好转,氧合指数提高,APACHEⅡ评分下降,机械通气及ICU住院时间缩短,病死率降低（P〈0.01或〈0.05）。结论 DCRRT能促进SAP并ALI患者的肺功能恢复,减少机械通气时间,缩短ICU住院时间,降低病死率。     

感染性休克早期PiCCO监测血管外肺水

目的探讨对感染性休克患者早期应用脉搏指示连续心排血量(Pi CCO)监测的临床意义。方法分析重症监护病房(ICU)收治的63例感染性休克患者的临床资料,分为Pi CCO组(33例)和CVP组(中心静脉压监测,30例),两组患者均进行液体复苏治疗,比较治疗结局及相关指标的差异。结果治疗72h后PICCO组患者的APACHEⅡ评分、血管活性药物评分、MAP、CI值均优于CVP组(P0.05)。PICCO组住院病死率、机械通气治疗时间低于CVP组,但差异不显著(P0.05)。结论 Pi CCO监测下指导液体复苏治疗能够提高第一次液体复苏成功率和缩短患者住院时间。     

脉搏指示连续心排血量监测指导急性呼吸窘迫综合征患者液体管理的临床研究

目的 研究脉搏指示连续心排血量(PiCCO)监测指导急性呼吸窘迫综合征(ARDS)患者液体管理的临床效果.方法 入选28例ARDS患者,随机分为干预组(n=15)和对照组(n=13),干预组在PiCCO监测下指导液体管理,对照组采用传统方法进行液体管理,治疗后统计两组患者一周内的血乳酸变化、氧合指数变化、机械通气时间、ICU住院时间及血管活性药物使用时间以及患者的28 d病死率,比较两组的差异.结果 两组患者一周内的血乳酸变化率差异无统计学意义(P=0.56),而干预组的氧合指数变化幅度明显较对照组大(140.0±26.4 vs 99.4±32.9,P=0.31),干预组患者机械通气时间明显短于对照组(21.8±3.5 vs 26.8±2.8,P=0.04),而ICU住院时间和血管活性药物使用时间的比较,差异无统计学意义.干预组患者的28 d病死率降低(60.0％ vs 69.2％),但差异无统计学意义(P＞0.05).结论 PiCCO监测指导ARDS患者液体管理可以改善患者的氧合,减少机械通气时间,但还不能显著降低患者的28 d病死率.     

脉搏指示连续心排血量监测指导重症急性胰腺炎连续性血液净化治疗

目的：探讨脉搏指示连续心排血量（PiCCO）监测对指导重症急性胰腺炎（SAP）患者血液净化的应用价值。 方法：按血液动力学监测方法的不同将51例行连续性血液净化（CBP）治疗的SAP患者分为2组：观察组23例,行PiCCO监测,测得心指数(CI)、胸腔内血容量指数（ITBI）、血管外肺水指数（ELWI）等指导CBP期间的液体管理;对照组28例,监测血压、心率、平均动脉压（MAP）、中心静脉压（CVP）等,按常规方法管理液体。记录2组患者治疗前及治疗后24、48、72h的急性生理与慢性健康状况评估(APACHEⅡ）评分、氧合指数（OI）、低血压发生率,并统计CBP持续时间、住ICU时间及病死率。 结果：治疗前2组APACHEⅡ评分、OI比较,差异无统计学意义（均P＞0.05）。经CBP治疗后48、72h,与对照组比较,观察组患者低血压发生率及APACHEⅡ评分明显更低,而OI明显更高（均P<0.05）。2组患者24、48、72h的脱水量、24h入量、住ICU 时间、 CBP时间差异有统计学意义(均P<0.05)。结论：PiCCO监测指标适用于指导SAP患者CBP期间的容量管理,对指导SAP患者CBP治疗具有较高的临床价值。     

脉波指示连续心排量监测技术在多发伤患者液体复苏中的应用

目的 观察脉波指示连续心排量监测（PICCO）技术在多发伤患者液体复苏中的应用效果.方法 将36例多发伤患者随机分为治疗组和对照组各18例.治疗组经股动脉放置PICCO动脉导管,经颈内静脉或锁骨下静脉放置双腔或三腔中心静脉导管,根据PICCO指标变化指导液体复苏;对照组行中心静脉导管留置,根据中心静脉压（CVP）、血乳酸、心率（HR）及尿量等指导液体复苏.记录两组治疗前（T0）及治疗后6 h（T1）、12 h（T2）、24h（T3）的HR、CVP、平均动脉压（MAP）、氧合指数（PaO2/FiO2）,72 h复苏液体量,呼吸机应用时间,ICU住院时间,28d内病死率.结果 两组T1、T2 、T3时的HR均低于T0,CVP、MAP、PaO2/FiO2均高于T0,P均≤0.01;治疗组T2、T3时的HR、CVP、MAP均低于对照组,PaO2/FiO2均高于对照组,P均≤0.01.治疗组72 h复苏液体量（14451.7±162.9）mL、呼吸机应用时间（7.1±3.57）h、ICU住院时间（9.5±3.92）d、28 d内病死率11.1％,对照组分别为（21520.6±178.2）mL、（15.2 ±3.79）h、（22.1 ±4.15）d、22.2％,P均≤0.05.结论 HCCO技术能有效地指导多发伤患者的液体复苏,减少72 h复苏液体量,缩短呼吸机应用时间和ICU住院天数,降低病死率.     

老年重症肺炎并发感染性休克患者血管外肺水与液体管理

目的探讨脉搏指示连续心排血量(PiCCO)技术监测血管外肺水指数(ELWI)对老年重症肺炎并发感染性休克患者液体管理的指导意义。 方法2011年8月至2014年7月杭州市老年病医院ICU选取46例老年重症肺炎机械通气患者,其中以ELWI为目标进行容量管理22例(ELWI组),以中心静脉压(CVP)结合胸部影像学为参照进行容量管理24例(CVP组),观察两组患者24 h,48 h,72 h的APACHEⅡ评分、氧合指数、血乳酸、中心静脉血氧饱和度(ScVO₂)、液体出入量、机械通气时间、ICU住院时间及28 d病死率的变化。两组患者APACHEⅡ评分、氧合指数、血乳酸、ScVO₂、液体出入量、机械通气时间、ICU住院时间的比较均采用独立样本t检验,28d病死率的比较采用χ²检验。 结果与CVP组比较,ELWI组在24 h,48 h的APACHEⅡ评分及24 h的氧合指数、ScVO₂、血乳酸均未发生明显变化,差异均无统计学意义(t＝12.43、5.63、11.32、13.65、10.64、8.63,均P>0.05);而72 h的APACHEⅡ评分明显下降,48 h,72 h的氧合指数、ScVO₂明显升高,72 h的血乳酸明显降低,差异均有统计学意义(t＝26.45、5.12、45.23、4.16、15.43、16.22,均P<0.05)。与CVP组比较,ELWI组24 h,48 h液体总入量及净入量均明显减少,差异均有统计学意义(t＝18.42、25.64、3.32、11.82,均P<0.05);而72 h的液体总入量及净入量均未发生明显变化,差异均无统计学意义(t＝6.13、26.52,均P>0.05)。与CVP组比较,ELWI组机械通气时间及ICU住院时间均明显减少,差异均有统计学意义(t＝18.55、22.12,均P<0.05);28 d病死率未发生明显变化,差异无统计学意义(χ²＝0.55,P>0.05)。 结论老年重症肺炎并发感染性休克患者进行PiCCO技术监测,根据ELWI指导液体复苏,能显著降低液体总入量,明显改善患者氧合指数,减少呼吸机使用时间,缩短ICU住院时间,降低病死率。     

Characterization of MTHFR,GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes in childhood acute leukemia

The role of methylenetetrahydrofolate reductase (MTHFR C677T), glutathione S-transferases (GSTM1 and GSTT1 null, GSTP1 Ile105Val), and cytochromes p450 (CYP1A1*2A) genotypes in the etiology of childhood leukemia was simultaneously investigated. 144 Turkish children with acute lymphoblastic leukemia (ALL) and 33 with acute nonlymphoblastic leukemia (ANLL) were studied and compared with 185 healthy pediatric controls. The frequency of MTHFR genotype was insignificantly higher in ALL (7.7%) and ANLL (6.3%) than in controls (4.4%). Equal distribution of the GSTM1 null genotype was detected between ALL patients and controls (55%), while its incidence was slightly higher in ANLL patients (61.3%). Although GSTT1 null genotype was insignificantly lower in ALL patients (20.9%) than controls (22.7%), it was significantly underrepresented in ANLL patients (6.5%) (P = 0.05, OR 0.24, 95% CI 0.05-1.03). The homozygous frequency of GSTP1 genotype did not differ significantly between groups of ALL (3.7%), ANLL patients (9.1%) and controls (4.9%). Homozygous CYP1A1*2A genotype was underrepresented in ALL patients (1%) as compared to control (4.8%) but the differences did not reach to statistical significance (OR 0.21; 95% CI 0.03-1.72). Homozygosity for this genotype was not detected in ANLL patients. No particular association was noted between different combinations of combined genotypes and risk of development of childhood ALL and ANLL. These results suggested that there are no significant associations between the studied genotypes and the risk of developing either form of acute leukemia except GSTT1 null and homozygosity for CYP1A1 genotypes that may play protective roles in the development of ANLL in Turkish children.     

The polymorphisms of GSTM1, GSTT1, HYL1*2, and XRCC1, and aflatoxin B1-related hepatocellular carcinoma in Guangxi population, China.

AIM: High incidence rates of hepatocellular carcinoma (HCC) in Guangxi, China, are primarily due to heavy aflatoxin B1 (AFB1) exposure via corn and groundnut consumption. This study was designed to examine the polymorphisms associated of three carcinogen-metabolizing genes (namely: GSTM1, GSTT1, and HYL1*2) and one DNA-repair gene (namely: XRCC1), and investigate their role as susceptibility markers for HCC. METHODS: We conducted a case-control study including 257 cases of cancer and 649 hospital-based age, sex, ethnicity, and hepatitis B virus infection-matched controls to examine the role of genetic polymorphisms of four genes (GSTM1, GSTT1, HYL1*2, and XRCC1) in the context of HCC risk for the Guangxi population. Genomic DNA isolated from 2ml whole blood was used to genotype GSTM1, GSTT1, HYL1*2, and XRCC1 by means of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. RESULTS: GSTT1-null genotype was not significantly associated with the risk of HCC, but GSTM1-null genotype [adjusted odds ratio (OR)=2.29, 95% confidence interval (CI)=1.59-3.31], HYL1*2 genotypes with 113 His allele (namely: YH/HH, adjusted OR=2.55, CI=1.78-3.65), and XRCC1 genotypes with 399 Gln allele (namely: AG/GG, adjusted OR=2.47, CI=1.72-3.54) increased the HCC risk. Compared with those individuals who did not express any putative risk genotypes as reference (OR=1), individuals featuring all of the putative risk genotypes [GSTM1-null, HYL1*2-YH/HH, and XRCC1-AG/GG] did experience a significantly greater cancer risk (adjusted OR=10.83, CI=5.44-21.59, P(interaction)<0.01). Additionally, the risk of HCC did appear to differ more significantly among individuals featuring risk genotypes and high-level or long-term AFB1 exposure, whose adjusted ORs (CIs) were 52.44 (17.51-157.08) and 326.93 (38.58-2770.52), respectively. CONCLUSIONS: The results suggest that carcinogen metabolism and DNA-repair pathways may simultaneously modulate the risk of HCC for Guangxi population, and, particularly for these having high-level or long-term AFB1 exposure.     

MChip, a low density microarray, differentiates among seasonal human H1N1, North American swine H1N1, and the 2009 pandemic H1N1

Please cite this paper as: Heil et al. (2010) MChip, a low density microarray, differentiates among seasonal human H1N1, North American swine H1N1, and the 2009 pandemic H1N1. Influenza and Other Respiratory Viruses 4(6), 411–416. Background  The MChip uses data from the hybridization of amplified viral RNA to 15 distinct oligonucleotides that target the influenza A matrix (M) gene segment. An artificial neural network (ANN) automates the interpretation of subtle differences in fluorescence intensity patterns from the microarray. The complete process from clinical specimen to identification including amplification of viral RNA can be completed in <8 hours for under US$10. Objectives  The work presented here represents an effort to expand and test the capabilities of the MChip to differentiate influenza A/H1N1 of various species origin. Methods  The MChip ANN was trained to recognize fluorescence image patterns of a variety of known influenza A viruses, including examples of human H1N1, human H3N2, swine H1N1, 2009 pandemic influenza A H1N1, and a wide variety of avian, equine, canine, and swine influenza viruses. Robustness of the MChip ANN was evaluated using 296 blinded isolates. Results  Training of the ANN was expanded by the addition of 71 well‐characterized influenza A isolates and yielded relatively high accuracy (little misclassification) in distinguishing unique H1N1 strains: nine human A/H1N1 (88·9% correct), 35 human A/H3N2 (97·1% correct), 31 North American swine A/H1N1 (80·6% correct), 14 2009 pandemic A/H1N1 (87·7% correct), and 23 negative samples (91·3% correct). Genetic diversity among the swine H1N1 isolates may have contributed to the lower success rate for these viruses. Conclusions  The current study demonstrates the MChip has the capability to differentiate the genetic variations among influenza viruses with appropriate ANN training. Further selective enrichment of the ANN will improve its ability to rapidly and reliably characterize influenza viruses of unknown origin.     

Analysis of HLA-DRB1, DQA1, DQB1 haplotypes in Sardinian centenarians

Some genetic determinants of longevity might reside in those polymorphisms for the immune system genes that regulate immune responses. Many longevity association studies focused their attention on HLA (the human MHC) polymorphisms, but discordant results have been obtained. Sardinians are a relatively isolate population and represent a suitable population for association studies. Some HLA-DR and DQ alleles form very stable haplotypes with a strong linkage disequilibrium. In a previous study on Sardinian centenarians we have suggested that HLA-DRB1 *15 allele might be marginally associated to longevity. HLA-DR,DQ haplotypes are in strong linkage disequilibrium and well conserved playing a role in the association to diseases. Hence, we have evaluated, by amplification refractory mutation system/polymerase chain reaction (ARMS-PCR) the HLADQA1 and HLA-DQB1 allele frequencies in 123 centenarians and 92 controls from Sardinia to assess whether the association to HLA-DRB1 *15 allele may be due to the other genes involved in the HLA-DR,DQ haplotypes. The frequencies of HLA-DQA1, DQB1 haplotypes were not significantly modified in centenarians. Nevertheless by evaluating the frequency of DRB1 *15 linked haplotypes, we observed a not significant increase in centenarians of HLA-DQA1 *01, DQB1 *05 and HLA-DQA1 *01,DQB1 *06 haplotypes. These data suggest that these haplotypes might have a role in determining life span expectancy and longevity.     

CYP1A1 , GSTM1 , GSTT1 and NQO1 polymorphisms and colorectal adenomas in Japanese men

AIM: To investigate the role of functional genetic poly-morphisms of metabolic enzymes of tobacco carcinogens in the development of colorectal adenomas. METHODS: The study subjects were 455 patients with colorectal adenomas and 1052 controls with no polyps who underwent total colonoscopy in a preretirement health examination at two Self Defense Forces hospitals. The genetic polymorphisms studied wereCYP1A1*2A (rs 4646903), CYP1A1*2C (rs 1048943), GSTM1 (null or non-null genotype), GSTT1 (null or non-null genotype) and NQO1 C609T (rs 1800566). Genotypes were determined by the polymerase chain reaction (PCR)-restriction fragment length polymorphism or PCR method using genomic DNA extracted from the buffy coat. Cigarette smoking and other life-style factors were ascertained by a self-administered questionnaire. The associations of the polymorphisms with colorectal adenomas were examined by means of OR and 95%CI, which were derived from logistic regression analysis. Statistical adjustment was made for smoking, alcohol use, body mass index and other factors. The gene-gene interaction and effect modification of smoking were evaluated by the likelihood ratio test. RESULTS: None of the five polymorphisms showed a significant association with colorectal adenomas, nor was the combination of GSTM1 and GSTT1 . A borderline significant interaction was observed for the combination of CYP1A1*2C and NQO1 (P = 0.051). The OR associated with CYP1A1*2C was significantly lower than unity among individuals with the NQO1 609CC genotype. The adjusted OR for the combination of the CYP1A1*2C allele and NQO1 609CC genotype was 0.61 (95%CI: 0.42-0.91). Although the interaction was not statistically significant (P = 0.24), the OR for individuals carrying the CYP1A1*2C allele and GSTT1 null genotype decreased significantly compared with those who had neither CYP1A1*2C allele nor GSTT1 null genotype (adjusted OR: 0.69, 95%CI: 0.49-0.97). Smoking did not modify the associations of the individual polymorphisms with colorectal adenomas. There w     

Association analyses of genetic polymorphisms of GSTM1, GSTT1, NQO1, NAT2, LPL, PRSS1, PSTI, and CFTR with chronic alcoholic pancreatitis in Japan

Background: Excessive consumption of alcohol is involved in the onset of pancreatitis. However, most of heavy drinkers do not always develop chronic pancreatitis. Various genetic factors appear to be involved in these individual differences in onset of chronic alcoholic pancreatitis. Here we investigated a possible association of alcoholic pancreatitis with polymorphisms of the various genes belong to the phase II detoxification enzymes responsible for metabolism of the oxidative compounds, and the several genes that have relevance to inherited pancreatitis. Methods: The subjects consisted of 53 patients with chronic alcoholic pancreatitis, 54 alcoholic patients without pancreatic dysfunction, and 42 healthy individuals. DNA was extracted from the peripheral nucleated blood cells of all subjects and genetic mutations and subtypes were analyzed by the PCR and RFLP methods. We examined the correlation between chronic alcoholic pancreatitis and variants of the phase II detoxification enzymes such as Glutathione S-transferase M1 (GSTM1), glutathione S-transferase theta 1 (GSTT1), NADPH-quinone oxidoreductase 1 (NQO1), and N-acetyl transferase (NAT2). In addition, genes of lipoprotein lipase (LPL), cationic trypsinogen (PRSS1), pancreatic secretory trypsin inhibitor (PSTI), and cystic fibrosis transmembrane conductance regulator (CFTR) were also analyzed. Results: Frequencies of the gene deletion of GSTM1 and GSTT1 in addition to the C-allele frequency of NQO1 tended to be higher in the alcoholic patients with (AlCP) or without pancreatic dysfunction (Alc) than in the healthy controls although the difference was not significant. The NAT2 gene showed no relation with Alc and AlCP patients. PSTI, LPL, PRSS1, and CFTR genes presented no association with chronic alcoholic pancreatitis. Conclusions: All genes analyzed in the present study lacked association with chronic alcoholic pancreatitis. However, the gene deletion of GSTM1 and GSTT1, and the C-allele of NQO1 cannot be ruled out for association with alcoholism.     

Role of CYP2D6, CYP1A1, CYP2E1, GSTT1, and GSTM1 genes in the susceptibility to acute leukemias

Acute leukemias (ALs) are heterogeneous diseases. Functional polymorphisms in the genes encoding detoxification enzymes cause inter-individual differences, which contribute to leukemia susceptibility. The CYP2D6, CYP1A1, CYP2E1, GSTT1, and GSTM1 polymorphisms in ALL (n = 156) and AML (n = 94) patients and 140 healthy controls were genotyped by PCR and/or PCR-RFLP using blood or bone marrow samples. No association was observed between the GSTT1 gene deletion and patients (OR = 0.8, 95% CI = 0.4-1.7 for AMLs and OR = 0.9, 95% CI = 0.5-1.6 for ALLs). Patients with ALL and AML had a higher prevalence of the GSTM1 deletions compared to controls but only the difference among adult AML patients (OR = 2.1, 95% CI = 1.0-4.2) was statistically significant. The CYP2D6*3 variant allele frequency was lower in the overall acute leukemia patients (0.6%) compared to controls (P = 0.03). CYP2D6*1/*3 genotype frequency also showed a protective association in AML patients (OR = 0.09, 95% CI = 0.01-1.7; P = 0.04). We also found a risk association for CYP2E1*5 in ALL and AML (OR = 3.6, 95% CI = 1.4-9.4 and OR = 3.9, 95% CI = 1.4-10.5, respectively). No association was found for the studied CYP2D6*4, CYP1A1*2A, and GSTT1"null" variants and the risk of acute leuke-mia (ALL or AML). This case-control study suggests a contribution of CYP2E1, CYP2D6, and GSTM1 "null" variants to the development of acute leukemias.     

胰腺癌组织Shh、Gli1、Sufu、TAK1、p-TAK1蛋白的表达及其临床意义

目的 探讨Hedgehog信号通路重要成员Shh、Gli1、Sufu以及TAK1和磷酸化TAK1(p-TAK1)在胰腺癌组织中的表达及其与临床病理参数的相关性.方法 应用免疫组化法检测38例手术切除的胰腺癌组织及其配对的癌旁胰腺组织中Shh、Gli、Sufu、TAK1、p-TAK1蛋白的表达,分析它们与临床病理参数间的关系及它们相互间的关系.结果 胰腺癌组织Shh、Gli1、Sufu、TAK1、p-TAK1蛋白的表达率分别为86.8％(33/38)、52.6％(20/38)、68.4％(26/38)、55.3％(21/38)、52.6％(20/38),而癌旁胰腺组织中的表达均为阴性.Gli1表达与肿瘤远处转移及临床分期呈正相关(r值分别为0.524、0.361,P值均＜0.05);Sufu表达与患者性别相关(r=-0.378,P＜0.05);TAK1表达与胰腺癌临床分期呈正相关(r=0.468,P＜0.05);p-TAK1表达与临床分期、肿瘤远处转移呈正相关(r值分别为0.418、0.361,P值均＜0.05).胰腺癌组织中Gli1的表达水平与TAK1及p-TAK1呈正相关(P＜0.05).结论 Hedgehog信号通路及TAK1途径在胰腺癌的发生、发展中具有一定作用,且两条途径可能存在一定的相互作用.     

CYP1A1, CYP2E1, GSTM1, GSTT1, EPHX1 exons 3 and 4, and NAT2 polymorphisms, smoking, consumption of alcohol and fruit and vegetables and risk of head and neck cancer

Purpose As risk-modifiers of alcohol and tobacco effects, metabolic genes polymorphisms were investigated as susceptibility candidates for squamous cell carcinoma of the head and neck (SCCHN). Methods A total of 210 cases and 245 hospital controls, age and gender matched, were genotyped for CYP1A1, CYP2E1, GSTM1, GSTT1, EPHX1 exons 3 and 4, and NAT2 polymorphisms. A measurement of the biological interaction among two risk factors was estimated by the attributable proportion (AP) due to interaction and its 95% confidence interval (CI). Results SCCHN risk was associated with high-levels of alcohol intake [OR = 3.50 (95%CI: 1.93–6.35) and OR = 6.47 (95%CI: 2.92–14.35) for 19–30 g/day and >30 g/day, respectively], cigarette smoking [OR = 3.47 (95%CI: 1.88–6.41) and OR = 7.65 (95%CI: 4.20–13.90) for 1–25 and >25 pack-years of smoking, respectively] and low-fruit and vegetables consumption (OR = 2.45; 95%CI: 1.53–3.92). No differences were observed for the genotypes or haplotypes distributions among cases and controls, and no biological interaction emerged from gene–gene and gene–environment interaction analyses. An attributable proportion (AP) due to biological interaction of 0.65 (95%CI: 0.40–0.90) was detected for heavy drinkers with a low intake of fruit and vegetables, and an AP of 0.40 (95%CI: 0.10–0.72) resulted forever smokers with low fruit and vegetables consumption. Conclusions Even in presence of high alcohol consumption or cigarette smoking, a high intake of fruit and vegetables might prevent the development of around one quarter of SCCHN cases. The lack of interaction between the studied polymorphisms and the environmental exposures suggests that chronic consumption of tobacco and alcohol overwhelm enzyme defences, irrespective of genotype.