己酮可可碱在高机械通气诱导大白鼠肺损伤炎性反应中的作用

目的探讨己酮可可碱(pentoxifylline,PTX)在大容量机械通气诱导的大白鼠肺损伤炎性反应中的作用。方法大白鼠在接受4h大容量机械通气时,治疗组(8只)静脉给予PTX,对照组(15只)静脉给予生理盐水,比较通气前后气道灌洗液中血栓烷B2(thromboxane B2,TXB2)、肿瘤坏死因子α(tumor necrosis factor-alpha,TNF-α)、血小板活性因子(platelet activating factor,PAF)、肺组织髓过氧化物酶(myeloperoxidase,MPO)水平和肺组织湿干重量比。结果气道灌洗液中TXB2治疗组通气前为(17±4)ng/L,通气后为(13±1)ng/L,对照组通气前为(15±2)ng/L,通气后为(21±2)ng/L,两组通气后比较差异有统计学意义(P<0.01);TNF-α治疗组通气前为(39±19)ng/L,通气后为(245±76)ng/L,对照组通气前为(29±16)ng/L通气后为(620±112)ng/L,两组通气后比较差异有统计学意义(P<0.01);PAF两组通气后比较差异无统计学意义。治疗组肺组织MPO为(0.6±0.1)OD/g,对照组为(1.4±0.7)OD/g(P<0.01);治疗组肺组织湿干重量比为(6.3±0.3)g/g,对照组为(7.3±0.4)g/g(P<0.01)。结论PTX在抑制大容量机械通气诱导大白鼠肺损伤的炎性反应中有一定的积极作用。     

Chromosomal aberrations in cord blood are associated with prenatal exposure to carcinogenic polycyclic aromatic hydrocarbons.

Molecular and traditional epidemiology studies have indicated a possible relationship between in utero environmental exposures and increased risk for childhood cancers, especially acute leukemias. Chromosomal aberrations have been associated with environmental exposures and cancer risk in adults. In order to more clearly define the association between prenatal exposures to carcinogenic polycyclic aromatic hydrocarbons (PAH) and chromosomal aberrations, chromosomal aberration frequencies were measured in a subset of 60 newborns from the Columbia Center for Children's Environmental Health (CCCEH) Prospective Cohort Study. The subset was composed of African American and Dominican, nonsmoking mother-newborn pairs residing in low-income neighborhoods of New York City, who were exposed to varying levels of airborne PAHs. Prenatal exposure was assessed by questionnaire, personal air monitoring during the third trimester, and PAH-DNA adducts in umbilical cord blood. Chromosomal aberrations were measured in cord blood lymphocytes by fluorescence in situ hybridization. PAH-DNA adducts were not associated with chromosomal aberrations. However, airborne PAHs were significantly associated with stable aberration frequencies in cord blood (P < 0.01). Moreover, stable aberration frequencies were significantly higher among African American newborns compared with Dominican, despite no significant differences in PAH exposure. These results show for the first time an association between prenatal exposure to airborne carcinogenic PAHs and chromosomal aberrations in cord blood, suggesting that such prenatal exposures have the potential to cause cytogenetic damage that has been related to increased cancer risk in other populations. If confirmed, this finding may open new avenues for prevention.     

Single-agent versus combination chemotherapy in advanced non-small-cell lung cancer: the cancer and leukemia group B (study 9730).

PURPOSE: We compared the efficacy of combination chemotherapy versus single-agent therapy in patients with advanced non-small-cell lung cancer. PATIENTS AND METHODS: A total of 561 eligible patients were randomly assigned to receive paclitaxel alone or in combination with carboplatin. RESULTS: The response rate was 17% in the paclitaxel arm and 30% in the carboplatin-paclitaxel arm (P < .0001). Median failure-free survival was 2.5 months in the paclitaxel arm and 4.6 months in the carboplatin-paclitaxel arm (P = .0002). Median survival times were 6.7 months (95% CI, 5.8 to 7.8) and 8.8 months (95% CI, 8.0 to 9.9), and 1-year survival rates were 32% (95% CI, 27% to 38%), and 37% (95% CI, 32% to 43%), respectively. The overall survival distributions were not statistically different: hazard ratio = 0.91 (95% CI, 0.77 to 1.17; P = .25). Hematological toxicity and nausea were more frequent in the combination arm, but febrile neutropenia and toxic deaths were equally low in both arms. There was no significant survival difference in elderly patients. Performance status 2 patients treated with combination chemotherapy had a better survival rate than those treated with single-agent therapy (P = .019). CONCLUSION: Combination chemotherapy improves response rate and failure-free survival compared with single-agent therapy, but there was no statistically significant difference in the primary end point of overall survival. The results in elderly patients were similar to younger patients. Performance status 2 patients had a superior outcome when treated with combination chemotherapy.     

Regional differences in milk and complementary feeding patterns in infants participating in an international nutritional type 1 diabetes prevention trial

Differences in breastfeeding, other milk feeding and complementary feeding patterns were evaluated in infants at increased genetic risk with and without maternal type 1 diabetes (T1D). The Trial to Reduce IDDM in the Genetically at Risk is an international nutritional primary prevention double‐blinded randomized trial to test whether weaning to extensively hydrolyzed vs. intact cow's milk protein formula will decrease the development of T1D‐associated autoantibodies and T1D. Infant diet was prospectively assessed at two visits and seven telephone interviews between birth and 8 months. Countries were grouped into seven regions: Australia, Canada, Northern Europe, Southern Europe, Central Europe I, Central Europe II and the United States. Newborn infants with a first‐degree relative with T1D and increased human leukocyte antigen‐conferred susceptibility to T1D were recruited. A lower proportion of infants born to mothers with than without T1D were breastfed until 6 months of age in all regions (range, 51% to 60% vs. 70% to 80%). Complementary feeding patterns differed more by region than by maternal T1D. In Northern Europe, a higher proportion of infants consumed vegetables and fruits daily compared with other regions. Consumption of meat was more frequent in all European regions, whereas cereal consumption was most frequent in Southern Europe, Canada and the United States. Maternal T1D status was associated with breastfeeding and other milk feeding patterns similarly across regions but was unrelated to the introduction of complementary foods. Infant feeding patterns differed significantly among regions and were largely inconsistent with current recommended guidelines.     

Workshop report on the extraction of foetal DNA from maternal plasma

OBJECTIVE: Cell free foetal DNA (cff DNA) extracted from maternal plasma is now recognized as a potential source for prenatal diagnosis but the methodology is currently not well standardized. To evaluate different manual and automated DNA extraction methods with a view to developing standards, an International Workshop was performed. METHODS: Three plasma pools from RhD-negative pregnant women, a DNA standard, real-time-PCR protocol, primers and probes for RHD were sent to 12 laboratories and also to one company (Qiagen, Hilden, Germany). In pre-tests, pool 3 showed a low cff DNA concentration, pool 1 showed a higher concentration and pool 2 an intermediate concentration. RESULTS: The QIAamp DSP Virus Kit, the High Pure PCR Template Preparation Kit, an in-house protocol using the QIAamp DNA Blood Mini Kit, the CST genomic DNA purification kit, the Magna Pure LC, the MDx, the M48, the EZ1 and an in-house protocol using magnetic beads for manual and automated extraction were the methods that were able to reliably detect foetal RHD. The best results were obtained with the QIAamp DSP Virus Kit. The QIAamp DNA Blood Mini Kit showed very comparable results in laboratories that followed the manufacturer's protocol and started with > or = 500 microL plasma. One participant using the QIAamp DNA Blood Midi Kit failed to detect reliably RHD in pool 3. CONCLUSIONS: This workshop initiated a standardization process for extraction of cff DNA in maternal plasma. The highest yield was obtained by the QIAamp DSP Virus Kit, a result that will be evaluated in more detail in future studies.