Protective effect of blood transfusions on postoperative recurrence of Crohn's disease in parous women

BACKGROUND: Perioperative blood transfusion (BT) appeared to have adverse effects on survival after surgery for malignant tumors while pretransplantation BT suppressed allograft rejection. Interest grew in the effect of BT on postoperative recurrence of Crohn's disease. STUDY DESIGN AND METHODS: To determine the effect of perioperative BT on the recurrence of Crohn's disease after primary surgery, the medical histories of 148 patients with Crohn's disease, 62 males and 86 females (49 nonparous and 37 parous), were reviewed. Eighty-seven patients received perioperative BT. RESULTS: Overall, perioperative BT showed no effect on recurrence. Patients with Crohn's disease limited to the ileum had a better prognosis with regard to recurrence than did patients with Crohn's disease located in the colon or located in both ileum and colon, but the difference was not significant. Perioperative transfusion seemed to protect against recurrent disease after colon resection, which might be explained by the fact that colon resections, which often necessitate perioperative BT, generally result in a shorter bowel segment at risk for recurrent disease. Overall, parous women showed a worse prognosis than nonparous females and men (p = 0.022). Transfusions had a beneficial effect in parous women (p = 0.068) and, after correction for type of operation, this beneficial effect was significant (p = 0.026). After perioperative BT, parous women had a similar prognosis with respect to recurrent Crohn's disease as nonparous females and men. CONCLUSION: Perioperative BT has a beneficial effect on the postoperative recurrence of Crohn's disease in parous women.     

Development and maturation of postural reflexes in normal kittens

Electrical stimulation of the hypothalamus in rats anesthetized with chloralose-urethane evoked antidromic responses in 5% of the neurons in the nucleus tractus solitarius (NTS) which responded orthodromically to vagus nerve stimulation. The NTS neurons with such a direct forebrain projection (F-NTS neurons) were distributed mostly in the lateral part of the ipsilateral commissural NTS. Latencies of the antidromic responses ranged from 20 to 75 ms, indicating that the axons of the F-NTS neurons were unmyelinated. Orthodromic responses (latencies, 20 to 80 ms) were observed in 6 of 23 F-NTS neurons, to the same stimuli that evoked the antidromic responses. Sites that elicited antidromic responses in the F-NTS neurons upon stimulation covered almost all medial hypothalamic nuclei, but 65% were localized in the preoptic-anterior hypothalamic region. All orthodromic responses to activation of vagal afferent fibers (either myelinated or unmyelinated) were polysynaptic in nature. Three F-NTS neurons were found to project to two different hypothalamic regions, by axonal branching. In addition, the firing rate of most F-NTS neurons was not appreciably affected by norepinephrine-induced blood pressure increase. It is concluded that vagal visceral input is transmitted polysynaptically to the F-NTS neurons and is then conveyed to the forebrain via the direct pathway.     

Bone mineral density in sclerosteosis; affected individuals and gene carriers

BACKGROUND: Sclerosteosis is an autosomal recessive sclerosing bone disorder due to deficiency of sclerostin, a protein secreted by the osteocytes that inhibits bone formation. In the present study we assessed the effect of variable expression of the genetic defect on bone mineral density (BMD) in patients and carriers of the determinant gene. METHODS: We studied 25 individuals (seven patients and 18 phenotypically normal heterozygotes). BMD was measured by dual x-ray absorptiometry at the lumbar spine, total hip, and distal forearm, and lateral radiographs of the skull were obtained. RESULTS: Individuals with sclerosteosis had markedly increased BMD at all skeletal sites (Z-score ranges: lumbar spine, +7.73 to +14.43; total hip, +7.84 to +11.51; forearm, +4.44 to +9.53). In heterozygotes, BMD was above the mean value of healthy age-matched individuals at all skeletal sites and had a wide range of normal and clearly increased values. Skull radiographs showed the typical hyperostotic changes in affected individuals and mild or no changes in heterozygotes. CONCLUSIONS: Heterozygous carriers of sclerosteosis have BMD values consistently higher than the mean of healthy subjects without any of the bone complications encountered in homozygotes. This finding suggests that the production and/or activity of sclerostin can be titrated in vivo, leading to variable increases in bone mass without any unwanted skeletal effects, a hypothesis of obvious significance for the development of new therapeutics for osteoporosis.     

Endothelial lipase and reverse cholesterol transport in type 2 diabetes mellitus

Aims/Introduction:  Endothelial lipase (EL) plays an important role in high‐density lipoprotein (HDL) metabolism and experimental data suggest that EL might be proatherogenic. We have investigated whether serum EL concentration is associated with changes in serum capacity to induce cholesterol efflux and arterial stiffness in type 2 diabetes.Materials and Methods:  Serum EL was assayed by ELISA in 172 diabetic patients and 175 controls. The ability of serum to induce cholesterol efflux was measured using a cell culture system and arterial stiffness was determined by measuring pulse wave velocity (PWV) between carotid and femoral arteries.Results:  Diabetic patients had significantly higher C‐reactive protein (CRP) and EL (27.7 ± 16.6 ng/mL vs 24.0 ± 11.3, P < 0.05). Cholesterol efflux to serum mediated through scavenger receptor class B type I was impaired (15.1 ± 2.5%vs 16.7 ± 3.1, respectively, P < 0.01). In controls, serum EL correlated with cholesterol efflux to serum (r = −0.16, P = 0.025), but only a trend was seen in the diabetic patients. Linear regression showed that in controls, HDL, serum EL and waist circumference were major independent determinants of cholesterol efflux; whereas in the diabetic cohort, the major independent determinants of cholesterol efflux were HDL, CRP and age. PWV was increased in the diabetic patients (P < 0.01), but no association between serum EL and PWV was seen in either groups.Conclusions:  Serum EL was increased in diabetic patients, but impaired serum capacity to induce cholesterol efflux in these patients was mainly related to low HDL and subclinical inflammation. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00016.x, 2010)     

血管内皮生长因子对梗阻性肾病中肾小管周围毛细血管的调节作用

目的:观察刚断乳雄性SD大鼠单侧输尿管完全梗阻模型中血管内皮生长因子对肾小管周围毛细血管形态学变化的调节作用,探讨血管内皮生长因子在肾病进展中的生物活性作用。方法:实验于2005-03/2006-05在苏州大学儿科研究所完成。①实验材料:30只清洁级刚断乳雄性SD大鼠,体质量50～70g。②实验过程:结扎SD大鼠左侧输尿管建立单侧输尿管完全梗阻模型。于术后0,1,7,14,28d,分别随机选择6只模型大鼠,收获肾脏标本。③实验评估:采用苏木精-伊红染色观察肾积水的严重程度;Masson染色观察肾小管间质纤维化程度;PAS染色观察肾小管萎缩程度;免疫组织化学方法检测肾小管周围毛细血管的密度和血管内皮生长因子的表达水平;原位末端标记法对肾小管周围毛细血管和肾小管上皮细胞进行原位凋亡测定;透射电镜显示超微结构变化;血管内皮生长因子蛋白的表达强度和间质纤维化程度采用Leica图像分析系统检测。结果:①梗阻第1周,肾小管上皮细胞胞浆里的血管内皮生长因子染色在局部有增强,胎肝激酶1阳性肾小管周围毛细血管数量变化不显著,肾小管上皮细胞凋亡很少见,间质纤维化轻。第2,4周,血管内皮生长因子表达逐渐下降,直至在一些肾小管内完全消失。与此同时,胎肝激酶1阳性的肾小管周围毛细血管数量减少,肾小管扩张或萎缩明显,间质纤维化严重。②电镜显示肾小管上皮细胞、肾小管周围毛细血管内皮细胞的死亡形式主要为凋亡。③原位末端标记法显示肾小管上皮细胞凋亡在第14天达到高峰,然后迅速下降。④在梗阻第2周时,原位末端标记法阳性的肾小管周围毛细血管内皮细胞数与血管内皮生长因子表达面积百分比负相关(r=-0.668,P<0.05);肾小管周围毛细血管密度与血管内皮生长因子表达面积百分比正相关(r=0.707,P<0.05),而与肾小管上皮细胞凋亡负相关(r=-0.863,P<0.01)。结论:肾小管周围毛细血管减少与肾小管上皮细胞内血管内皮生长因子的表达不足相关,并与肾小管上皮细胞凋亡相关。     

The Williams syndrome chromosome 7q11.23 hemideletion confers hypersocial, anxious personality coupled with altered insula structure and function

Although it is widely accepted that genes can influence complex behavioral traits such as human temperament, the underlying neurogenetic mechanisms remain unclear. Williams syndrome (WS), a rare disorder caused by a hemizygous deletion on chromosome 7q11.23, including genes important for neuronal migration and maturation (LIMK1 and CLIP2), is typified by a remarkable hypersocial but anxious personality and offers a unique opportunity to investigate this open issue. Based on the documented role of the insula in mediating emotional response tendencies and personality, we used multimodal imaging to characterize this region in WS and found convergent anomalies: an overall decrease in dorsal anterior insula (AI) gray-matter volume along with locally increased volume in the right ventral AI; compromised white-matter integrity of the uncinate fasciculus connecting the insula with the amygdala and orbitofrontal cortex; altered regional cerebral blood flow in a pattern reminiscent of the observed gray-matter alterations (i.e., widespread reductions in dorsal AI accompanied by locally increased regional cerebral blood flow in the right ventral AI); and disturbed neurofunctional interactions between the AI and limbic regions. Moreover, these genetically determined alterations of AI structure and function predicted the degree to which the atypical WS personality profile was expressed in participants with the syndrome. The AI's rich anatomical connectivity, its transmodal properties, and its involvement in the behaviors affected in WS make the observed genetically determined insular circuitry perturbations and their association with WS personality a striking demonstration of the means by which neural systems can serve as the interface between genetic variability and alterations in complex behavioral traits.     

开通闭塞冠状动脉策略的全球性研究GUSTO-Ⅲ(亚组研究)

治疗方案 患者按2:1比例随机分配。或接受reteplase 1000万 U静脉注射、30min后再次静脉注射;或接受alteplase加速化滴注治疗,90min内剂量     

Effective stimulation of donors for granulocyte transfusions with recombinant methionyl granulocyte colony-stimulating factor [see comments]

Effective granulocyte transfusion (GT) therapy has been hampered by the low yield of neutrophil granulocytes (PMN) obtainable from normal donors even by use of corticosteroid prestimulation, hydroxyethyl starch (HES), and modern leukapheresis (LA) techniques. To increase the PMN yield we performed LA in 22 healthy volunteer donors after a single subcutaneous administration of 300 micrograms of granulocyte colony- stimulating factor (G-CSF) 12 to 16 hours before LA. Five to 7 L of blood was processed within 1.9 to 3 hours using the standard CS- 3000Plus (Baxter, Deerfield, IL) LA protocol including HES. The mean number of PMN harvested was 44.32 +/- 15.5 x 10(9), corresponding to 6.88 +/- 2.1 x 10(9)/L of blood processed. In the final product PMN functions (in vitro: chemotaxis, phagocytosis, chemiluminescence, superoxide anion production; in vivo: chemiluminescence, half-life) were at least normal. In all donors G-CSF induced a consistent increase of white blood cell (mean 16.46 +/- 3.8 x 10(9)/L) and PMN counts (15.94 +/- 3.6 x 10(9)/L). No G-CSF-related side effects were observed and LA was well tolerated. G-CSF prestimulation allows to harvest three to five times higher numbers of functionally normal PMN by LA compared with corticosteroid pretreatment. This may help to overcome one of the major limitations of an effective PMN support.