血管紧张素原基因5’端启动子区A-20C和A-6G单核苷酸多态性与蒙古族人群原发性高血压的相关性

目的:分析血管紧张素原基因启动子区A-20C和A-6G单核苷酸多态性与蒙古族人群原发性高血压的相关性。方法:实验于2005-08/2006-01在北京华大实验室完成。选取对象均为生活在内蒙古乌拉特后旗的蒙古族牧民,三代血亲内无其他民族。采用基因测序技术对内蒙古蒙古族人群中107例原发性高血压患者和108例正常对照者进行A-20C和A-6G基因分型,观察高血压组和正常对照组不同基因型的分布和等位基因频率的差异。结果:①两组受试者在性别、年龄及吸烟、饮酒、体质量指数和临床化验检查指标有较好的匹配(P均>0.05)。②两组血管紧张素原基因A-20C位点AA,AC,CC基因型频率比较差异无显著性意义(高血压组分别为0.51,0.29,0.20;正常对照组分别为0.49,0.28,0.23,χ2=0.395,P=0.529)。A,C等位基因频率比较差异无显著性意义(高血压组分别为0.65,0.35;正常对照组分别为0.63,0.37,χ2=0.015,P=0.904)。③两组血管紧张素原基因A-6G位点AA,AG,GG基因型频率比较差异无显著性意义(高血压组分别为0.50,0.33,0.17;正常对照组分别为0.55,0.34,0.11,χ2=1.924,P=0.165)。A,G等位基因频率比较差异无显著性意义(高血压组分别为0.66,0.34;正常对照组分别为0.72,0.28,χ2=1.728,P=0.189)。④高血压组协同存在血管紧张素原基因A-20C基因型CC时,血管紧张素原基因A-6G基因型GG频率稍高于正常对照组,但差异无显著性意义(χ2=2.395,P=0.122,OR=7.52,95%CI0.014～1.250),高血压组G等位基因明显高于正常对照组(分别为0.37,0.22,χ2=4.658,P=0.034),携带该等位基因的蒙古族人群发生原发性高血压的相对危险度升高(OR=2.80,95%CI1.087～7.271)。结论:血管紧张素原基因A-20C和A-6G单核苷酸多态性与蒙古族人群原发性高血压相关,并可能具有协同作用。     

A clinical study assessing the tolerability and biological effects of infliximab, a TNF-alpha inhibitor, in patients with advanced cancer

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) is an important regulator of the chronic inflammation contributing to tumour progression. Infliximab, an anti-TNF-alpha monoclonal antibody was investigated in this trial of patients with advanced cancer. The primary objectives were to determine the safety profile and biological response of infliximab in a cancer population. Clinical response was a secondary objective. PATIENTS AND METHODS: Forty-one patients received infliximab at 5 mg/kg (n = 21) or 10 mg/kg (n = 20) i.v. at 0 and 2 weeks and then every 4 weeks. Post-treatment samples were measured for changes in plasma and serum TNF-alpha, CCL2, IL-6 and C-reactive protein (CRP). RESULTS: Infliximab was well tolerated with no dose-limiting toxic effects. At both doses of infliximab, neutralisation of serum TNF-alpha was observed after 1 h while plasma CCL2, IL-6 and serum CRP were decreased 24 and 48 h following infliximab administration. Seven patients experienced disease stablisation (range 10-50+ weeks). There was no evidence of disease acceleration in any patient. CONCLUSIONS: Infliximab treatment was safe and well tolerated in patients with advanced cancer. There was evidence of biological activity with baseline TNF-alpha and CCL2 being correlated with infliximab response.     

Middle cerebral artery flow velocity waveforms in normal and small-for-gestational-age fetuses.

The middle cerebral artery flow velocity waveforms were obtained in 16 normal fetuses in a longitudinal study and in 128 normal fetuses in a cross-sectional study with pulsed Doppler ultrasonography. The pulsatility index values of the middle cerebral artery were higher at 25 to 30 weeks' gestation than those observed during the two periods of major cerebral cellular multiplication in the human fetus. In 9 of the 16 fetuses studied longitudinally we compared the pulsatility index values obtained at the end of gestation with those obtained at 1 month after delivery; no significant difference was observed. The pulsatility index of the middle cerebral artery was also determined in 33 small-for-gestational-age fetuses. A middle cerebral artery pulsatility index value below our normal range was recorded in 9 of the 33 small-for-gestational-age fetuses (27.3%). These small-for-gestational-age fetuses with abnormal pulsatility index values had a significantly higher incidence of abnormal fetal heart rate and admission into the neonatal intensive care unit. There were three deaths in the nine small-for-gestational-age fetuses with abnormal pulsatility index values (33.3%) and three deaths in the 24 small-for-gestational-age fetuses with normal pulsatility index values (12.5%). Our data indicate that the pulsatility index of the middle cerebral artery in the normal human fetus has a parabolic pattern during pregnancy and does not change significantly after delivery. The results suggest that the small-for-gestational-age fetus with a normal middle cerebral artery pulsatility index is at lower risk than the fetus with abnormal pulsatility index values; moreover, management of the small-for-gestational-age fetus may be aided by the study of the middle cerebral artery waveforms.     

Estimation of fetal weight with the use of head, body, and femur measurements--a prospective study

In utero estimates of fetal weight were evaluated prospectively in 109 fetuses with the use of sonographic models developed in a previous study. This report confirms that the best in utero weight estimates result from the use of models based on measurements of head size, abdominal size, and femur length. Since the accuracy of these models (1 SD = 7.5%) is significantly better than those based on measurements of head and body (e.g., biparietal diameter, abdominal circumference), we recommend routine use of such models in obstetric sonography.     

Mathematic modeling of fetal growth: development of individual growth curve standards

To provide a more precise means for monitoring individual fetal growth and to improve the detection of growth abnormalities, the Rossavik growth model [P = c(t)k + s(t)] has been used to establish individual growth curve standards. A longitudinal study of the growth of one-dimensional (biparietal diameter, head, and abdominal circumferences), two-dimensional (head and abdominal profile areas), and three-dimensional (head and abdominal volumes) parameters in 18 normal fetuses has revealed that the growth of all parameters can be well-described by the Rossavik model (R2: 97.2 to 99.5%). Strong statistical evidence was obtained indicating that the coefficient k is principally a geometric coefficient having a value determined primarily by the dimension of the parameter being studied. It was also found that the coefficients c and s can be estimated from the data obtained before 28 weeks' conceptual age. Individual growth curve models derived from data obtained before 28 weeks were capable of predicting growth beyond 28 weeks. These models provide growth curve standards for evaluating individual fetal growth beyond 28 weeks.     

The effect of intrauterine malnutrition on the term infant. A 14-year progressive study

The developmental outcome of 33 newborn infants with clinical intrauterine malnutrition at birth and 13 clinically well nourished infants from a middle to high socio-economic population have been followed from birth to 12-14 years of age. Psychometric studies revealed a lowering of the IQ score in malnourished infants compared to well nourished infants (104 +/- 15 compared to 121 +/- 13, p less than 0.05) and a need for special education (p less than 0.03). Forty-five percent of the malnourished infants' birth weights were above the 10th percentile on the Colorado Intrauterine Growth Grid. The Full Scale IQ of malnourished infants with BW greater and less than 10th percentile on the Colorado Intrauterine Growth Grid were comparable. Malnourished infants with birth weights greater than 10th percentile had lower IQ scores than well nourished infants (101 +/- 13 compared to 121 +/- 13, p less than 0.006). Thirty-nine percent of the infants with handicaps would have been missed if only infants with birth weights less than 10th percentile were considered high risk.