Infants born to narcotic dependent mothers: Physical growth patterns in the first 12 months of life

Objectives: To describe the physical growth patterns of infants born to narcotic dependent mothers (INDM) over a 12 months period and, if possible, to relate the growth to drug taking patterns during pregnancy.
Methodology: The growth of a cohort of 43 INDM was measured during the first 12 months of life. Weight and length measurements were compared with percentile charts and converted to Z scores. Questionnaire data about drug taking practices, demographic variables and the neonatal period (including withdrawal scores) were obtained.
Results: Twenty-four (55.8%) of INDM had evidence of neonatal drug withdrawal requiring treatment with phenobarbitone. At birth, Z scores for weight and length indicated relative intrauterine growth retardation. By 12 months, there had been some catch up growth, but Z scores for weight and length were still below zero. Persistent weight retardation at 12 months was correlated with methadone dosage during pregnancy, but not the need for phenobarbitone therapy.
Conclusions: The growth patterns of INDM in the first 12 months of life indicated that at birth there was evidence of intrauterine growth retardation, but by 12 months the growth was little different from the rest of the community. There appears to be some influence of narcotic agents taken while pregnant on subsequent growth of INDM.     

Identification of differentially expressed genes in aflatoxin B1- treated cultured primary rat hepatocytes and Fischer 344 rats

Aflatoxin B1 (AFB1), a mutagen and hepatocarcinogen in rats and humans, is a contaminant of the human food supply, particularly in parts of Africa and Asia. AFB1-induced changes in gene expression may play a part in the development of the toxic, immunosuppressive and carcinogenic properties of this fungal metabolite. An understanding of the-role of AFB1 in modulating gene regulation should provide insight regarding mechanisms of AFB1-induced carcinogenesis. We used three PCR- based subtractive techniques to identify AFB1-responsive genes in cultured primary rat hepatocyte RNA: differential display PCR (DD-PCR), representational difference analysis (RDA) and suppression subtractive hybridization (SSH). Each of the three techniques identified AFB1- responsive genes, although no individual cDNA was isolated by more than one technique. Nine cDNAs isolated using DD-PCR, RDA or SSH were found to represent eight genes that are differentially expressed as a result of AFB1 exposure. Genes whose mRNA levels were increased in cultured primary rat hepatocytes after AFB1 treatment were corticosteroid binding globulin (CBG), cytochrome P450 4F1 (CYP4F1), alpha-2 microglobulin, C4b-binding protein (C4BP), serum amyloid A-2 and glutathione S-transferase Yb2 (GST). Transferrin and a small CYP3A-like cDNA had reduced mRNA levels after AFB1 exposure. Full-length CYP3A mRNA levels were increased. When liver RNA from AFB1-treated male F344 rats was evaluated for transferrin, CBG, GST, CYP3A and CYP4F1 expression, a decrease in transferrin mRNA and an increase in CBG, GST, CYP3A and CYP4F1 mRNA levels was also seen. Analysis of the potential function of these genes in maintaining cellular homeostasis suggests that their differential expression could contribute to the toxicity associated with AFB1 exposure.      

Glomerular size in renal dysplasia secondary to obstructive uropathy: a further exploration of the fetal lamb model

BACKGROUND/PURPOSE: Creating an obstructive uropathy early in glomerulogenesis would produce multicystic dysplastic kidneys (MCDK). Measuring the mean planar area of the glomeruli (GMPA) may clarify the pathogenesis of MCDK. METHODS: Fetal lambs at 60 days' gestation had their left ureter ligated and were delivered by cesarian section at 145 days' gestation. Kidney weight and length were recorded. GMPA in 3 zones (outer, middle, inner) of the sectioned kidney was measured using a computerized planimeter. The obstructed kidneys were compared with contralateral unobstructed kidneys. The unpaired Student's t test was used to determine significance. RESULTS: One ewe miscarried. Four of 5 (80%) 60-day lambs survived. All had dysplastic kidneys. Mean kidney weights were 4.3 +/- 0.84 g in MCDK and 16.8 +/- 3.6 g in controls (P< .05). The GMPA of the outer, middle, and inner zones of the MCDK were 2.7 x 10(-3) mm2, 3.2 x 10(-3) mm2, and 4.0 x 10(-3) mm2, respectively. Controls were 2.8 x 10(-3) mm2, 4.4 x 10(-3) mm2, and 6.0 x 10(-3) mm2. The glomeruli of 60-day fetal kidneys were 3.0 x 10(-3) mm2, 6.1 x 10(-3) mm2, and 11.0 x 10(-3) mm2. MCDK had smaller glomeruli in the inner and middle zones than controls. CONCLUSION: Fetal glomeruli appear to grow from the inner zone of the kidney. Early urinary tract obstruction stops this growth.     

选择性头部降温对胎羊缺血性脑损伤纹状体神经元凋亡和星形胶质细胞增殖的影响

目的研究选择性头部降温对缺血性脑损伤胎羊纹状体神经元凋亡和星形胶质细胞增殖的影响。方法胎羊于妊娠117~124d时通过双侧颈动脉阻塞30min造成双侧脑缺血损伤,损伤后将胎羊随机分为:损伤组(n=10)、2h低温组(损伤后2h开始亚低温治疗,n=7)和6h低温组(损伤后6h开始亚低温治疗,n=8),另设正常对照组(n=5)。通过冷循环水进行选择性头部降温,取脑组织用免疫组化法检测胎羊纹状体caspase-3(半胱天冬氨酸酶-3),GFAP(胶质纤维酸性蛋白)和PCNA(增殖细胞核抗原)的表达。结果①纹状体神经元凋亡:正常对照组中,caspase-3表达极少(11.00±13.77),损伤组caspase-3免疫阳性细胞为177.70±48.69,明显增加(P=0.000),损伤后2h治疗组(54.14±39.44,P=0.000)和损伤后6h治疗组(122.43±52.36,P=0.017)均能减少caspase-3免疫阳性细胞。②纹状体星形胶质细胞增殖:与正常对照组(163.40±21.98)相比,缺血性脑损伤组的GFAP免疫阳性细胞明显增多(433.25±66.69,P=0.000),损伤后2h开始亚低温治疗(219.50±35.31,P=0.000)和损伤后6h开始亚低温治疗(272.50±86.20,P=0.000)均能减少GFAP免疫阳性细胞。③纹状体PCNA阳性细胞的表达:在正常对照组中,PCNA免疫阳性细胞较少,为153.40±12.46,缺血性脑损伤组的PCNA免疫阳性细胞明显增多(353.70±45.60,P=0.000),损伤后2h开始亚低温治疗(187.14±26.26,P=0.000)和损伤后6h开始亚低温治疗(230.25±67.46,P=0.000)均能减少PCNA免疫阳性细胞。结论亚低温可以抑制纹状体神经元的凋亡和星形胶质细胞的增殖,该作用可能为选择性头部降温的脑保护作用机制之一。     

Upper half body irradiation (UHBI) for extensive small cell carcinoma of the lung

Upper half body irradiation (UHBI) was given to 41 of 121 patients with extensive small cell carcinoma of the lung. All patients were treated with 6 courses of cyclophosphamide, doxorubicin, and vincristine (CAV). Responding patients also received prophylactic cranial irradiation and local irradiation to prechemotherapy intrathoracic disease. Among the 70% (85/121) of patients who responded to chemotherapy, 41 have received UHBI, given one to two months later. The single fraction midline dose given has been increased in successive patients from 300 to 720 cGy (uncorrected for inhomogeneities). Actual lung doses were higher by 9-22%, (determined in 31 patients by CT scanning and lung density measurements). Adverse effects seen were vomiting, fever, drowsiness, myelosuppression, liver dysfunction and dry mouth. All were transient, and no pneumonitis or treatment deaths occurred. Adverse effect rates were similar at all dose levels. UHBI is well tolerated in patients who have received chemotherapy and merits further study.     

恶性肿瘤靶向给药的临床应用

恶性肿瘤靶向给药是指利用具有一定肿瘤靶向性的导向分子（载体）携带治疗肿瘤的药物,在肿瘤局部选择性杀伤肿瘤细胞（及转移的肿瘤细胞）,以避免药物的全身毒副作用,提高疗效的一种治疗方法．由于抗癌药物在杀伤肿瘤细胞的同时也杀伤正常细胞,增加了全身的毒副作用．因此,近几年来,对恶性肿瘤靶向治疗的研究突飞猛进,发展了人源性抗HER-2mAb、依西美坦、放射性核素、