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.     

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。     

Endothelial cell activation markers and delayed cerebral ischaemia in patients with subarachnoid haemorrhage

Background

Endothelial cell activation may be connected with the pathogenesis of delayed cerebral ischaemia (DCI) after subarachnoid haemorrhage (SAH).

Aim

To assess the relationship between serial concentrations of circulating markers of endothelial cell activation (soluble intercellular adhesion molecule‐1, soluble platelet selectin (sP‐selectin), soluble endothelial selectin, ED1‐fibronectin, Von Willebrand Factor (VWF) and VWF propeptide) and development of DCI.

Methods

687 blood samples were collected from 106 consecutive patients admitted within 72 h after onset of SAH. Changes in levels were analysed in the last sample before and in the first sample after the onset of DCI (n = 30), and in subgroups with DCI occurring within 24 h after treatment of the aneurysm (n = 12) or unrelated to treatment of the aneurysm (n = 18). Patients without DCI (n = 56) served as controls.

Results

Concentrations of sP‐selectin, but not of the other markers, were found to increase considerably after DCI unrelated to treatment of the aneurysm (increase 25 ng/ml, 95% CI 8 to 43), whereas they tended to decrease in the control patients without DCI (decrease 13 ng/ml, 95% CI −28 to 2.4). Surgery was found to profoundly influence the levels of the markers irrespective of the occurrence of DCI.

Conclusion

The rise in sP‐selectin level during DCI is suggested to be the result of platelet activation, as levels of the other markers of endothelial cell activation were not increased after DCI unrelated to treatment. Whether a causal role of platelet activation is implicated in the development of DCI should be determined in further studies in which the relationship between concentrations of markers and treatment is taken into account.Endothelial cell activation may have a role in the pathogenesis of delayed cerebral ischaemia (DCI) after subarachnoid haemorrhage (SAH).^1,2 Activated endothelial cells express several receptors on their cell membrane. The inflammatory cell adhesion molecules intercellular adhesion molecule‐1 (ICAM‐1), P (platelet)‐selectin and E (endothelial)‐selectin participate in rolling, firm adhesion and transmigration of leucocytes along the vessel wall. ICAM‐1 is constitutively expressed in low quantities on leucocytes, fibroblasts, epithelial cells and endothelial cells. Its expression increases on stimulation by cytokines.³ E‐selectin is found only on activated endothelium. P‐selectin is a membrane molecule of the α granules in platelets and of the endothelial Weibel–Palade bodies and is expressed on the cell membrane on activation of endothelial cells.⁴ ED1‐fibronectin (ED1‐fn) is an adhesive glycoprotein that is synthesised in endothelial cells. The ED1 domain is included in fibronectin molecules in pathological conditions of the vessel wall.⁵ Von Willebrand Factor (VWF) is a large adhesive glycoprotein participating in the adhesion of platelets. It is produced and released by vascular endothelial cells and, in much smaller amounts, by platelets. VWF is a marker of both acute and chronic endothelial cell activation. A recently developed assay is the measurement of VWF propeptide, which may serve as a marker of acute endothelial cell activation.⁶The synthesis of VWF propeptide is linked with the synthesis of VWF, but its plasma half life is shorter than that of VWF.We studied the relationship between serial concentrations of circulating markers of endothelial cell activation (soluble (s) ICAM‐1, sP‐selectin, sE‐selectin, ED1‐fn, VWF and VWF propeptide) and development of DCI in patients with SAH.     

Minactivin expression in human monocyte and macrophage populations

Adherent monolayer cultures of human blood monocytes, peritoneal macrophages, bone marrow macrophages, and colonic mucosa macrophages were examined for their ability to produce and secrete minactivin, a specific inactivator of urokinase-type plasminogen activator. All except colonic mucosa macrophages produced and secreted appreciable amounts of minactivin, but only blood monocytes were stimulated by muramyl dipeptide (adjuvant peptide) to increase production. The minactivin from each of these populations could be shown to preferentially inhibit urokinase-type plasminogen activator and not trypsin, plasmin, or "tissue"-type plasminogen activator (HPA66). A plasminogen-activating enzyme present in monocyte cultures appeared unaffected by the presence of minactivin and could be shown to be regulated independently by dexamethasone.     

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、     

"Stem cell" origin of the hematopoietic defect in dyskeratosis congenita

We have used the long-term bone marrow culture (LTBMC) system to analyze hematopoiesis in three patients with dyskeratosis congenita (DC), two of whom had aplastic anemia, and the third had a normal blood count (apart from mild macrocytosis) and normal BM cellularity. Hematopoiesis was severely defective in all three patients, as measured by a low incidence of colony-forming cells and a low level of hematopoiesis in LTBMC. The function of the marrow stroma was normal in its ability to support the growth of hematopoietic progenitors from normal marrows seeded onto them in all three cases, but the generation of hematopoietic progenitors from patients marrow cells inoculated onto normal stromas was reduced, thus suggesting the defect to be of stem cell origin. The parents and unaffected brother of one of the families have also been studied in LTBMC and all showed normal hematopoietic and stromal cell function. From this study we speculate that there are some similarities between DC and the defect in the W/Wv mouse.