Rhenium-188-Labeled DTPA: a new radiopharmaceutical for intravascular radiation therapy

Balloon angioplasty is a standard treatment for artherosclerotic coronary artery disease. However, its clinical value is reduced by a high restenosis rate. A new concept in preventing restenosis is the use of a liquid-filled balloon containing a beta-emitting radioisotope. In this study, we performed biodistribution studies of Re-188 perrhenate and Re-188 diethylenetriaminopentaacetate (DTPA) to assess the resulting organ dose values in the event of balloon rupture if these agents are used for the clinical inhibition of restenosis after percutaneous transluminal coronary angioplasty (PTCA). After injecting Re-188 preparations intravenously, rats were killed at 10 min, 30 min, 60 min, 2 h, and 6 h ( n =5 per group). Tissue concentrations were calculated and expressed as percent injected dose per gram or per milliliter (%ID/g or %ID/mL). In addition, urine excretion and thyroid gland uptake were evaluated in rats ( n=5 per group) with a gamma camera after administration of 37 MBq (1 mCi) of each agent. Our data showed that both agents were excreted primarily via urine. However, the excretion of Re-188 DTPA was much faster than that of Re-188 perrhenate via the urinary system. The biodistribution data revealed that radioactivity levels in the stomach and the thyroid gland were high in the perrhenate group but low in the Re-188 DTPA group. The concentration levels in other tissues including lung, liver, testis, muscle, and blood were low throughout this study for both agents. The thyroid radiation value in the Re-188 perrhenate group was 0.163 mGy/MBq, which was much higher than that of the Re-188 DTPA group (0.0167 mGy/MBq). The stomach radiation value was as high as 0.127 mGy/MBq for Re-188 perrhenate, compared with 0.013 mGy/MBq for Re-188 DTPA. In conclusion, in the event of balloon rupture, the release of Re-188 DTPA results in lower radiation doses than Re-188 perrhenate, especially to the thyroid gland and the stomach. Our data suggest that Re-188 DTPA is a useful radiopharmaceutical for endovascular irradiation.     

A comparison among nalbuphine, meperidine, and placebo for treating postanesthetic shivering

Postanesthetic shivering (PS) is distressing for patients and may induce a variety of complications. In this prospective, double-blinded, randomized study, we evaluated the value of nalbuphine, compared with meperidine and saline, for treating PS. Ninety adult patients were included in the study. Group 1 (n = 30) received i.v. nalbuphine 0.08 mg/kg, Group 2 (n = 30) received i.v. meperidine 0.4 mg/kg, and Group 3 (n = 30) received i.v. saline. Treatment that stopped shivering was considered to have been successful. The results demonstrated that, 5 min after treatment, both nalbuphine and meperidine provided a rapid and potent anti-shivering effect on PS, with high response rates of 80% and 83%, compared with those of saline (0%) (P < 0.01). Thirty minutes after injection, the response rates of nalbuphine and meperidine were 90% and 93%, respectively, compared with 17% in the saline group (P < 0.01). The differences between nalbuphine and meperidine were not significant. We conclude that nalbuphine may be an alternative to meperidine for treating PS. IMPLICATIONS: We evaluated nalbuphine versus meperidine and saline for treating postanesthetic shivering. Our results demonstrate that both nalbuphine and meperidine provide a similar rapid and potent anti-shivering effect. Nalbuphine may be an alternative to meperidine for treating postanesthetic shivering.     

Postoperative behavioral outcomes in children: effects of sedative premedication

BACKGROUND: Although multiple studies document the effect of sedative premedication on preoperative anxiety in children, there is a paucity of data regarding its effect on postoperative behavioral outcomes. METHODS: After screening for recent stressful life events, children undergoing anesthesia and surgery were assigned randomly to receive either 0.5 mg/kg midazolam in 15 mg/kg acetaminophen orally (n = 43) or 15 mg/kg acetaminophen orally (n = 43). Using validated measures of anxiety, children were evaluated before and after administration of the intervention and during induction of anesthesia. On postoperative days 1, 2, 3, 7, and 14, the behavioral recovery of the children was assessed using the Post Hospitalization Behavior Questionnaire. RESULTS: The intervention group demonstrated significantly lower anxiety levels compared with the placebo group on separation to the operating room and during induction of anesthesia (F[1,77] = 3.95, P = 0.041). Using a multivariate logistic regression model, the authors found that the presence or absence of postoperative behavioral changes was dependent on the group assignment (R = 0.18, P = 0.0001) and days after operation (R = -0.20, P = 0.0001). Post hoc analysis demonstrated that during postoperative days 1-7, a significantly smaller number of children in the midazolam group manifested negative behavioral changes. At week 2 postoperatively, however, there were no significant differences between the midazolam and placebo groups. CONCLUSIONS: Children who are premedicated with midazolam before surgery have fewer negative behavioral changes during the first postoperative week.     

A case-controlled MRI/MRA study of neurovascular contact in hemifacial spasm

BACKGROUND: Neurovascular contact (NVC) with the root exit zone (REZ) of the ipsilateral facial nerve is associated with hemifacial spasm (HFS), but unresolved issues remain. OBJECTIVES: To 1) determine the frequency of symptomatic and nonsymptomatic NVC, 2) determine the features of NVC associated with HFS, and 3) correlate severity of HFS to these features. METHODS: Two independent, blinded, prospective assessments of high-resolution MR and MR angiography (MRA) images were performed on Chinese cases (HFS: n = 44; age-matched control subjects: n = 20). RESULTS: Over 88% of 44 symptomatic sides in patients with HFS had NVC of the ipsilateral facial nerve. At least 80% of symptomatic sides involved NVC at the anterior aspect of the REZ [REZ(ant.)]. Although NVC was observed in approximately half of nonsymptomatic sides, at least 70% of them were not at REZ(ant.). NVC at the cisternal and intracanalicular portions of the facial nerve were not associated with HFS. Half of our patients with HFS had bilateral NVC, but none had bilateral symptoms. Most of our MR/MRA images showed that the size and position of the arterial branches of the vertebrobasilar system were markedly asymmetric. Of patients with bilateral NVC, over 83% had asymmetric NVC sites. The anterior inferior cerebellar artery was the most common vessel involved in NVC, but was not significantly associated with HFS. Most of the NVC involved one vessel at one contact point with no indentation. The development of HFS was significantly associated with nerve indentation in NVC. The development and severity of HFS were not associated with multiple contact points in NVC. No significant interobserver variability existed between the blinded assessments. CONCLUSIONS: MRI/MR angiography are accurate, fast, and safe in characterizing neurovascular contact (NVC) at the brainstem. The site of NVC and ipsilateral facial nerve indentation in NVC are significant determinants for the development of hemifacial spasm (HFS). The lack of bilateral NVC at the anterior aspect of the root exit zone of the facial nerve could explain in part the lack of bilateral symptoms. The development and severity of HFS are not associated with a specific blood vessel or multiple contact points in NVC.     

Effect of pulse pressure on vascular smooth muscle cell migration: the role of urokinase and matrix metalloproteinase

Plasminogen activator (PA) expression plays an important role in smooth muscle cell (SMC) migration and may therefore contribute to mechanical force-induced arterialization of vein grafts. The aim of this study was to determine whether pulse pressure due to pulsatile flow modulates SMC migration via urokinase (u-PA)-dependent mechanisms. Using a perfused transcapillary culture system, human umbilical vein SMC were exposed to pulse pressures (0-56 mmHg), in the absence or presence of human umbilical vein endothelial cells (EC) by varying pulsatile flow rates (0 ml/min to 25 ml/min). SMC cultured in the absence of EC increased their migration following exposure to increased pulse pressure (248+/-14%). Both u-PA and matrix metallo-proteinase 1 (MMP-1) expression was significantly elevated in SMC exposed to pressure as compared to static controls. The role of proteases in the pulse pressure-induced enhancement of SMC migration was confirmed following pretreatment with aprotinin, an anti u-PA antibody and metalloproteinase inhibitors (181+/-14% for aprotinin vs. 256+/-25% for control, 108+/-4% for anti-u-PA antibody vs. 233+/-17% for non-immune IgG, and 114+/-9% for BB-94, 105+/-7% for BB-3103 vs. 222+/-5% for control). Using SMC derived from u-PA gene knock-out mice, the SMC migratory response to increased pulse pressure was completely inhibited despite a significant increase in MMP expression in these cells. These results suggest that pulse pressure due to pulsatile flow induces SMC migration in vitro via u-PA and MMP-dependent mechanisms. Moreover, u-PA gene deletion results in blunting of pressure-induced SMC migration despite the endogenous upregulation of metalloproteinase. Modulation of u-PA expression by pressure may thus represent an important mechanism whereby hemodynamic forces regulate smooth muscle cell migration.     

α1-抗糜蛋白酶基因、早老素1基因 与阿尔茨海默病的相关分析

目的探讨中国汉族人中α１抗糜蛋白酶（ＡＡＣＴ）基因、早老素１（ＰＳ１）基因多态性与阿尔茨海默病（Ａｌｚｈｅｉｍｅｒｓｄｉｓｅａｓｅ,ＡＤ）的相关情况。方法应用ＰＣＲＲＦＬＰ方法,在１２３例患者和１４０例正常人中观察ＡＡＣＴ信号肽和ＰＳ１基因多态性的分布,进行关联分析。结果１ＡＤ患者与ＰＳ１基因等位基因１正关联,与等位基因２和基因型２／２负关联,但与１／１基因型无关;２ＡＡＣＴ信号肽基因多态性与ＡＤ无关联;３在三种ＰＳ１基因型中,ＡＡＣＴ信号肽基因多态性与ＡＤ均无关;４在ＡＡＣＴ基因ＡＡ、ＴＴ基因型中,ＰＳ１基因多态性与ＡＤ负关联,而ＴＡ型中ＰＳ１基因与ＡＤ无显著相关。结论中国人群中,ＡＤ与ＰＳ１基因２／２型负关联,而与ＡＡＣＴ信号肽基因多态性无关;ＡＡＣＴ信号肽和ＰＳ１基因多态性之间也无明显的相互影响。     

慢性癫痫大鼠脑组织生长抑素受体功能的变化

探讨癫痫发病的生化机制。方法用１２５Ｉ－ＳＯＭ作为配基,采用放射性配基受体结合分析法,对戊四氮诱导的慢性癫痫大鼠海马生长抑素（ＳＯＭ）受体功能进行了测定。结果慢性癫痫大鼠及对照组海马ＳＯＭ受体的Ｂｍａｘ值分别为２４６．０±１８．２ｐｍｏｌ／ｇ蛋白质及２２０．０±１５．３ｐｍｏｌ／ｇ蛋白质,Ｋｄ值分别为４．１９±０．３４ｎｍｏｌ／Ｌ及３．８９±０．２２ｎｍｏｌ／Ｌ。常用的抗痫药卡马西平（ＣＢＺ）、丙戌酸钠（ＶＰＡ）及钙桔抗剂尼莫地平（ＮＩＭ）能降低受体的亲和力,而苯妥因钠（ＰＨＴ）则无影响。结论ＳＯＭ受体活性增高在癫痫发病中起着重要作用,常用抗痫药的抗痫活性可能与其降低ＳＯＭ受体活性有关。     

Prothrombin activation in rabbits

The suitability of rabbit prothrombin activation fragment F 1.2 as a marker for the activation of the coagulation system was tested. Monoclonal antibodies to rabbit F 1.2 were raised, and a competitive F 1.2 ELISA was developed. Within the detection limit of the ELISA, no increase in rabbit F 1.2 was detected upon recalcification of plasma, whereas human F 1.2 increased 1500-fold. The apparent lack of F 1.2 formation in rabbit serum was confirmed by immunoblotting analysis of endogenous and biotin-labeled prothrombin. Meizothrombin and the B-chain of thrombin were the only prothrombin fragments detectable. In contrast, labeled human prothrombin formed, in addition, prethrombin 2 and F 1.2 in both human and rabbit serum. In contrast, rabbit F 1.2 formation could be demonstrated using purified rabbit prothrombin and factor Xa. These observations raise the possibility that rabbit prothrombin is less susceptible than the human counterpart to factor Xa cleavage at the 271/272 peptide bond. Thus, the primary structure of rabbit prothrombin was deduced by cDNA sequencing. While the 320/321 Xa cleavage site giving rise to meizothrombin was identical in rabbit and human prothrombin, the flanking region of the 271/272 Xa sensitive site contained a six amino acid deletion in the rabbit sequence. Taken together, these observations suggest that the observed differences between human and rabbit prothrombin activation may be due to different susceptibilities of the two Xa cleavage sites rather than plasma or serum cofactor(s).