The Effects of Serum from Patients with Acute Liver Failure on the Growth and Metabolism of Hep G2 Cells

In many bioartificial liver systems currently being designed and evaluated for use in fulminant hepatic failure, direct contact is required between the patient's blood and the liver cells in the device. The efficacy of such devices will be influenced by the interaction of fulminant hepatic failure (FHF) patient serum with the cells. We have found that FHF serum inhibits the growth rate and the synthesis of DNA, RNA, and protein; disturbs glutathione homeostasis; and induces morphological changes in cultured human Hep G2 cells. These interactions should influence the design of bioartificial liver devices based on proliferating cell lines and indicate the requirement to pretreat FHF patient plasma to reduce the toxin load.     

Effectiveness and cost-effectiveness of colorectal cancer screening: Selecting the ideal strategy

Abstract Colorectal cancer is the second most common cancer killer of Americans. Recently developed and tested methods of screening and surveillance can effectively diagnose and treat the disease in most patients before symptoms develop when the chance of cure is high. It is also possible to prevent colorectal cancer by detecting and resecting premalignant adenomatous polyps. Evidence-based guidelines recommend that the average-risk population greater than age 50 be screened with annual faecal occult blood tests plus periodic flexible sigmoidoscopy. This approach is feasible, efficacious, affordable and cost-effective in a high-risk country such as the US. Widespread compliance with these recommendations could reduce the mortality from this malignancy by more than 50%.     

异搏定对5-氟脲嘧啶抗肾癌效应的体外增效作用

在体外培养的肾透明细胞癌系中,观察了异搏定(Verapamil,VP)对5-氟脲嘧啶(Fluorouracil,5-Fu)细胞毒作用的影响。结果表明,异搏定在本身无细胞毒性的浓度下,可以显著增强5-氟脲嘧啶的细胞毒性,且增效作用随5-氟脲嘧啶浓度及异搏定浓度的增加及用药时间的延长而增强。     

Five different tests of reaction time evaluated in HIV seropositive men

In an attempt to develop a short neuropsychological test battery five different tests of reaction time were assessed according to their ability to discriminate between HIV seropositive men and healthy controls. In all tests a patient group with clinical symptoms was slower than the control group. In the complex reaction time test, which has a large cognitive aspect, even a clinically "asymptomatic" group was slower than the control group. The movement test, a new test with a large motor component, identified most slow responders, defining approximately half of the patients with clinical symptoms and one third of the "asymptomatic" patients as such. A test battery consisting of three tests is suggested for serial assessment and screening.     

Guinea pig maximisation test for skin sensitisation: the use of fewer test animals

Current European Community (Annex V) guidelines recommend the use of 20 test animals in the guinea pig maximisation test for skin sensitisation. The suitability, for classification and labelling purposes, of reducing the number of test animals has been examined by analysing the results of 40 studies submitted to the Health and Safety Executive, and by the use of a mathematical model. Our results suggest that in most cases an experiment with ten test animals can be used to determine satisfactorily whether a substance should be labelled with the risk phrase may cause sensitisation by skin contact. However, serious consideration should be given to the need for additional investigation if two or three of the ten test animals show a sensitisation response. The highest nonirritant concentration of a substance should be used at challenge. Clearer guidance in Annex V on evaluating challenge responses would be beneficial.     

Studies on the Level of Natural Antibodies Reactive with Various Tumor Cells during Urethane Carcinogenesis in BALB/c Mice

Serum from young normal BALB/c mice was found to contain IgM antibodies able tomediate complement-dependent lysis of certain syngeneic or allogeneic tumor target cells. The titer of such naturally occurring antitumor antibodies (NATA) was found to increase with aging.A longitudinal serological study comparing the cytotoxicity potential of NATA fromnormal and from urethan-treated BALB/c mice was performed. It was found that urethan-treated mice that did not develop primary lung-adenomas within the duration of the experi-ment had significantly lower NATA titers, against one out of 4 target cells assayed, than urethan-treated animals that developed lung adenomas. This difference was evident in two independent experiments. The results suggested that the lower NATA activity of the urethan-treated mice that did not develop tumors existed even before exposure to the carcinogenic insult. This raises the possibility that certain populations could be segregated according to their natural antibody profile into those individuals which will develop primary tumors within a certain period if exposed to a subthreshold amount of carcinogen, and those which will not.     

An Extension of the Regression of Offspring on Mid-Parent to Test for Association and Estimate Locus-Specific Heritability: The Revised ROMP Method

The Regression of Offspring on Mid-Parent (ROMP) method is a test of association between a quantitative trait and a candidate locus. ROMP estimates the trait heritability and the heritability attributable to a locus and requires genotyping the offspring only. In this study, the theory underlying ROMP was revised (ROMP_rev) and extended. Computer simulations were used to determine the type I error and power of the test of association, and the accuracy of the locus-specific heritability estimate. The ROMP_rev test had good power at the 5% significance level with properly controlled type I error. Locus-specific heritability estimates were, on average, close to simulated values. For non-zero locus-specific heritability, the proposed standard error was downwardly biased, yielding reduced coverage of 95% confidence intervals. A bootstrap approach with proper coverage is suggested as a second step for loci of interest.
ROMP_rev was applied to a study of cardiovascular-related traits to illustrate its use. An association between polymorphisms within the fibrinogen gene cluster and plasma fibrinogen was detected (p < 0.005) that accounted for 29% of the estimated fibrinogen heritability. The ROMP_rev method provides a computationally fast and simple way of testing for association and obtaining accurate estimates of locus-specific heritability while minimizing the genotyping required.     

血清谷氨酰转肽酶含量测定在慢性乙型肝炎中的临床意义

目的探讨血清谷氨酰转肽酶（GGT）含量变化在慢性乙型肝炎（CHB）不同程度肝脏病理损害中的变化规律及临床意义。方法测定70例CHB患者血清ALT、AST、GGT水平，同时行肝活体组织检查，对肝脏进行炎症分级和纤维分期。分析ALT、AST、GGT与CHB之间的关系。结果（1）ALT、AST、GGT随炎症程度和纤维化程度的上升而上升，但到G4和s4后则下降。GGT随ALT、AST的升高而升高，ALT、AST和GGT的相关系数分别为：0．322、0．328（P〈0．05）。在保肝治疗后，ALT较快降至正常且GGT保持在一个较低水平的为轻度CHB，而随着ALT下降，GGT仍持续在一个较高水平的为中度及重度CHB，其中重度CHB的GGT水平有所波动。结论血清GGT比ALT、AST更准确的反映肝脏的炎症程度，GGT的活动度给临床判断慢乙肝的炎症提供了重要的判断依据。     

终末期肝病模型评分在原发性肝癌合并肝硬化脾功能亢进外科治疗中的作用

目的 探讨终末期肝病模型(MELD)评分评估肝储备功能在原发性肝癌合并肝硬化脾功能亢进中确定手术适应证的应用价值.方法 对2001年1月至2007年1月间行肝癌切除联合脾切除(联合术)治疗的40例原发性肝癌合并肝硬化脾功能亢进患者的临床资料进行回顾性分析.通过MELD评分与Child-Pugh分级比较,结合临床资料及术后并发症分析,确定这一方法在评估肝储备功能中的作用.结果 同一Child-Pugh分级的患者MELD评分结果并不一致,在各级别间有交错现象.术后发生肝功能衰竭组(6例)的MELD评分均值为(24.6±6.6).未发生肝功能衰竭组(34例)的MELD评分均值为(16.3±8.5),差异有统计学意义(P<0.05).根据MELD评分分为A组16例(MELD评分<10),B组17例(MELD评分10-20),C组7例(MELD评分>20).A组术后肝功能衰竭发生率为0,B组为11.8%(2/17),C组为57.1%(4/7),差异有统计学意义(P<0.05).根据Child-Pugh分级分为Ⅰ级26例,Ⅱ级14例.Ⅰ级术后肝功能衰竭发生率为15.4%(4/26),Ⅱ级为14.3%(2/14),差异无统计学意义(P>0.05).结论 MELD评分能够较为客观地反映肝储备功能,对外科术式的选择、手术时机的确定有一定的参考作用.     

老年病人的术后认知功能障碍

术后认知功能障碍（POCD）定义为术后通过反复多次神经心理测试,患者的基本认知功能出现不同程度的损害。而早期术后认知功能及精神障碍更多见于老年患者。虽然POCD多见于心脏手术术后，但非心脏手术后发生POCD亦不少见，老年患者（年龄大于65岁）行心脏手术或非心脏手术，术后1周POCD的发生率分别为50%及26%。POCD的高危因素包括：高龄、术前认知受损以及酗酒等。POCD影响生活质量，加重社会负担并干扰药物治疗效果，延长患者住院周期。有必要深入的研究POCD的病因和神经功能保护的策略。