Excretory urography with iohexol: evaluation in children

A multicenter clinical study was conducted using iohexol, a second-generation nonionic contrast medium, for excretory urography performed in 130 children. Doses of iohexol (300 mg iodine/ml) ranged between 150 and 660 mgI/kg (0.5 and 2.2 ml/kg). Iohexol was tolerated well, and no significant adverse reactions occurred. Sixty-five iohexol urograms were evaluated to determine the minimum dose for adequate visualization of the kidneys and collecting systems. A dose greater than 300 mgI/kg (1.0 ml/kg) always resulted in a urogram of diagnostic quality, while visualization was insufficient for diagnosis in 10% of studies done with doses of 150-300 mgI/kg (0.5-1.0 ml/kg). Another 65 iohexol urograms were compared in a blinded manner with a similar number of studies performed using iothalamate meglumine at comparable iodine concentration and dose. Visualization of calyces and pelvoinfundibular structures achieved with iohexol was rated better with statistical significance, but there was no difference in visualization of the renal parenchyma or ureters. Use of iohexol in excretory urography may be advantageous in children who are at greatest risk for an adverse reaction to contrast media or in those most likely to benefit from use of a low osmolality contrast agent.     

Role of codon 160 in the sensitivity of human O6-alkylguanine-DNA alkyltransferase to O6-benzylguanine.

O6-Alkylguanine-DNA alkyltransferase (AGT) is a DNA repair protein that provides protection from alkylating agents such as dacarbazine, temozolomide, and 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), which are used for cancer chemotherapy. O6-Benzylguanine (BG) is an inhibitor of AGT that sensitizes tumors to these agents. BG is currently in clinical trials. It is possible that the presence of resistant forms of AGT may limit the effectiveness of this strategy. Previous studies have shown that the AGT mutant G160R, which may occur naturally as a result of a polymorphism in the AGT gene, is resistant to BG, whereas the mutants G160W and G160A are actually more sensitive to the inhibitor. To examine other mutations at this site, a random sequence was placed at codon 160 in the AGT cDNA, and a plasmid library was constructed to express these sequences in Escherichia coli. After selection with BG and N-methyl-N'-nitro-N-nitrosoguanidine, BG-resistant mutants were obtained and analyzed. Eleven different amino acid substitutions were found to impart BG resistance by this assay. The most resistant mutants contained histidine or arginine, which had EC50 values of 12 and 4.7 microM, respectively, compared with the wild-type EC50 of 0.08 microM, but nine other alterations led to at least a 10-fold rise in the EC50 value. Three additional mutations at codon 160 were constructed by site-directed mutagenesis, and these led to 6- to 11-fold increases in resistance to BG. Comparisons of the properties of mutants G160R and G160E showed that the presence of DNA enhanced the reaction with BG much more strongly when an acidic residue was present at this position. This may account for the lack of selection of the G160E mutation even though it did impart resistance to BG. These results indicate that many alterations of AGT at position 160 can lead to significant resistance to BG.     

Use of critical pathways to improve the care of patients with acute myocardial infarction.

PURPOSE: While critical pathways have become a popular strategy to improve the quality of care, their effectiveness is not well defined. The objective of this study was to investigate the effect of a critical pathway on processes of care and outcomes for Medicare patients admitted with acute myocardial infarction. SUBJECTS AND METHODS: A retrospective cross-sectional and longitudinal cohort study was made of Medicare patients aged 65 years and older hospitalized at 32 nonfederal Connecticut hospitals with a principal diagnosis of myocardial infarction during two periods: June 1, 1992, to February 28, 1993, and August 1, 1995, to November 30, 1995. The main endpoints of the cross-sectional analyses for the 1995 cohort were the proportion of patients without contraindications who received evidence-based medical therapies, length of stay, and 30-day mortality. Hospitals with specific critical pathways for patients with myocardial infarction were compared with hospitals without critical pathways. The main endpoints of the longitudinal analyses were change between 1992-93 and 1995 in the proportion of patients receiving evidence-based medical therapies, length of stay, and 30-day mortality. RESULTS: Ten hospitals developed critical pathways between 1992-93 and 1995. Eighteen of 22 nonpathway hospitals employed some combination of standard orders, multidisciplinary teams, or physician champions. Patients admitted to hospitals with critical pathways did not have greater use of aspirin within the first day, during hospitalization, or at discharge; beta-blockers within the first day or at discharge; reperfusion therapy; or use of angiotensin-converting enzyme inhibitors at discharge in 1995. The mean (+/- SD) length of stay in 1995 was not significantly different between pathway (7.8 +/- 4.6 days) versus nonpathway hospitals (8.0 +/- 4.2 days), and the change in length of stay between 1992-93 and 1995 was 2.2 days for pathway hospitals and 2.3 days for nonpathway hospitals. Patients admitted to critical pathway hospitals had lower 30-day mortality in 1995 (8.6% versus 11.6% for nonpathway hospitals, P = 0.10) and in 1992-93 (12.6% versus 13.8%, P = 0.39), but the differences were not statistically significant. CONCLUSIONS: Hospitals that instituted critical pathways did not have increased use of proven medical therapies, shorter lengths of stay, or reductions in mortality compared with other hospitals that commonly used alternative approaches to quality improvement among Medicare patients with myocardial infarction.     

The Natural Mentors of Adolescent Children of Alcoholics (COAs): Implications for Preventive Practices

Late adolescent children of alcoholics (COAs) were interviewed about their relationship with a natural mentor. Comparisons in social and emotional functioning were made to a matched sample of COAs who did not have a natural mentor. Results showed that a typical mentor was a same-sex relative who had been responsible for initiating the mentor-like relationship. Mentors' familiarity with adolescents' parents predicted the quality of the mentoring relationships. Differences in the reported adjustment of COAs with and without natural mentors are considered in light of prevention programming and its evaluation.     

组织工程细胞支架的免疫原性研究

目的：以组织工程血管脱细胞支架和仿生髓核组织工程细胞支架、周围神经去细胞神经基膜管为例,介绍组织工程脱细胞支架的免疫原性研究情况. 方法：应用计算机检索Medline 1997-01/2007-03关于免疫原性的文章.检索词“Immunotoxicology”并限定文章的语种类为English.同时利用计算机检索中国期刊全文数据库1997-01/2007-03的相关文章,限定文章语言种类为中文,检索词“组织工程,免疫原性”. 结果：主要组织相容性复合体Ⅰ免疫组织化学方法能够检测血管脱细胞支架的免疫原性;组织学观察及反转录-聚合酶链反应检测γ-干扰素、白细胞介素2、白细胞介素4、白细胞介素10 mRNA表达,可以反映仿生髓核组织工程支架的免疫原性;主要组织相容性复合体Ⅱ抗原可以反映出经过化学萃取后的去细胞预变性神经基膜血管结构保留较完整,免疫原性低. 结论：脱细胞可以极大地降低组织工程支架的免疫原性,从而使得组织工程产品有更广阔的使用前景.     

转化生长因子β1在白细胞介素1β诱导大鼠肾小管上皮细胞转分化及大黄素干预中的作用

目的:大黄素对白细胞介素1β诱导NRK52E细胞转分化有显著抑制作用。实验拟进一步观察转化生长因子β1在白细胞介素1β诱导大鼠肾小管上皮细胞-肌成纤维细胞转分化及大黄素抑制作用中的意义。方法:实验于2006-10/2007-05在泸州医学院附属医院免疫实验室完成。⑴实验材料及分组:以培养的大鼠肾小管上皮细胞株(NRK52E)为观察对象,按如下分组分别添加不同处理因素:①对照组:仅加入体积分数为0.05小牛血清的高糖DMEM培养基。②白细胞介素1β诱导组:加含白细胞介素1β终浓度为10μg/L的高糖DMEM培养基。③SB431542阻断组:加含白细胞介素1β终浓度为10μg/L及SB431542终浓度为10μmol/L的高糖DMEM培养基。④白细胞介素1β 大黄素组:同时加分别含白细胞介素1β终浓度为10μg/L及大黄素终浓度为25mg/L的高糖DMEM培养基。⑵实验评估:培养48h后用倒置相差显微镜观察细胞形态,细胞免疫化学染色法检测肌酸激酶、α-平滑肌肌动蛋白及转化生长因子β1的表达。结果:①白细胞介素1β可诱导部分细胞由卵圆形转变为梭形,且肌酸激酶表达减弱(P<0.01),α-平滑肌肌动蛋白及转化生长因子β1表达显著增强(P<0.01)。②SB431542特异性抑制转化生长因子β1作用后,白细胞介素1β诱导的细胞形态改变受抑,同时肌酸激酶表达增强(P<0.01),α-平滑肌肌动蛋白表达减弱(P<0.01),但转化生长因子β1的表达却无明显变化。③大黄素对白细胞介素1β诱导的细胞形态改变及肌酸激酶、α-平滑肌肌动蛋白的表达有明显抑制作用,其抑制作用与SB431542的作用相比无显著差异;同时,大黄素对白细胞介素1β诱导的转化生长因子β1的表达也有明显抑制作用(P<0.01)。结论:转化生长因子β1可能介导了白细胞介素1β诱导大鼠肾小管上皮细胞-肌成纤维细胞转分化,并参与了大黄素抑制白细胞介素1β诱导大鼠肾小管上皮细胞转分化的作用。     

Demographic characteristics and prevalence of serologic markers among donors who use the confidential unit exclusion process: the Retrovirus Epidemiology Donor Study

BACKGROUND: Most blood centers utilize a confidential unit exclusion (CUE) process, intended to reduce the risk of transfusion-associated infectious diseases by allowing high-risk donors confidentially to exclude their blood from use for transfusion. The effectiveness of this method remains controversial. STUDY DESIGN AND METHODS: Confirmatory or supplemental test results for antibodies to human immunodeficiency virus, human T-lymphotropic virus type I, and hepatitis C virus, as well as hepatitis B surface antigen and syphilis and screening test results for antibodies to hepatitis B core (antigen) and alanine aminotransferase levels were obtained for approximately 1.8 million units donated during 1991 and 1992 at five blood centers within the United States. The prevalences of these infectious disease markers in units that the donors confidentially excluded (CUE+) and units that the donors did not exclude (CUE-) were calculated and examined within demographic subgroups. RESULTS: Units that were CUE+ were 8 to 41 times more likely to be seropositive for antibodies to human immunodeficiency virus and hepatitis C virus, hepatitis B surface antigen, and syphilis and three to four times more likely to react for antibody to hepatitis B core (antigen) or to have elevated alanine aminotransferase levels than units that were CUE- (p < 0.001). The positive predictive value of CUE (the percentage of CUE+ units that were confirmed seropositive for any marker) was 3.5 percent, and the sensitivity of CUE (the percentage of confirmed-seropositive units that were CUE+) was 2.3 percent. CONCLUSION: The current CUE process has low sensitivity and apparently low positive predictive value, and in many cases, it appeared that donors misunderstood it. Yet, CUE was not a “random process,” as CUE+ units were more likely to be seropositive for any infectious disease marker than CUE- units. This suggests that efforts to improve the CUE system may be warranted. As risk factors for transfusion-transmitted infection become more difficult to identify by history-based screening, however, such efforts may have limited effect.     

Systemic antitumor immunity in experimental brain tumor therapy using a multimutated, replication-competent herpes simplex virus

Replication-competent, attenuated herpes simplex virus (HSV) vectors have been developed for viral oncolytic therapy of primary and metastatic malignant brain tumors. However, the role of the host immune responses in the brain has not been elucidated. N18 neuroblastoma cells were used as a tumor model in syngeneic A/J mice to test the therapeutic efficacy of G207, a conditionally replicating HSV vector, in an immunocompetent condition. G207 inoculated intraneoplastically exhibited a prominent oncolytic antitumor effect in mice harboring N18 tumors in the brain or subcutaneously, and, in addition, elicited a systemic antitumor immune response. Subcutaneous tumor therapy with G207 caused regression of a remote, established tumor in the brain or in the periphery, which was potentially mediated by the systemic antitumor immune response, and provided persistent tumor-specific protection against N18 tumor rechallenge in the brain as well as in the periphery. Antitumor immunity was associated with an elevation of specific CTL activity against N18 tumor cells that persisted for at least 13 months. The results suggest that the oncolytic antitumor action of replication-competent HSV may be augmented by induction of specific and systemic antitumor immunity effective both in the periphery and in the brain.