RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature

During the past decade, RGD-peptides have become a popular tool for the targeting of drugs and imaging agents to alphavbeta3-integrin expressing tumour vasculature. RGD-peptides have been introduced by recombinant means into therapeutic proteins and viruses. Chemical means have been applied to couple RGD-peptides and RGD-mimetics to liposomes, polymers, peptides, small molecule drugs and radiotracers. Some of these products show impressive results in preclinical animal models and a RGD targeted radiotracer has already successfully been tested in humans for the visualization of alphavbeta3-integrin, which demonstrates the feasibility of this approach. This review will summarize the structural requirements for RGD-peptides and RGD-mimetics as ligands for alphavbeta3. We will show how they have been introduced in the various types of constructs by chemical and recombinant techniques. The importance of multivalent RGD-constructs for high affinity binding and internalization will be highlighted. Furthermore the in vitro and in vivo efficacy of RGD-targeted therapeutics and diagnostics reported in recent years will be reviewed.     

儿童呼吸道苛养菌分离培养及药敏分析

目的：分析儿童呼吸道苛养菌的感染率及常用抗生素的耐药状况。方法：采用儿童呼吸道2050份咽拭子及痰标本进行苛养菌分离培养与鉴定，并对其中617株苛养菌做了药敏试验，结果：显示275株肺炎链球菌，耐药率较高的有红霉素81.1%，苯唑西林76.9%，复方磺胺甲恶唑76.9%，四环素65.4%；104株流感嗜血杆菌、184株副流感嗜血杆菌、54株卡他莫拉菌对氨苄西林耐药率分别为17.6%,28.9%,64.9%，对亚胺培南/西司他丁耐药率分别为16.4%，16.5%，0，同时复方磺胺甲恶唑的耐药率也分别高达56.7%，56.7%，64.9%。结论：提示苛养菌在儿童呼吸道感染中占有重要的地位，及时掌握这类细菌的耐药动态，对合理使用抗生素，延缓耐药株的产生有极其重要的临床意义。     

近端/远端复合肌肉动作电位振幅比率在术后面神经功能评估上的价值

目的 探讨近端/远端复合肌肉动作电位振幅比率在术后面神经肿瘤侵犯段功能评估上的价值和对早期面神经修复的指导意义。方法 比较术末面神经近端/远端复合肌肉动作电位振幅比率和术后2周、6个月患侧面神经功能的H-B分级之间的关系。结果 术后6个月面神经H-B分级恢复到Ⅰ-Ⅱ级者,术末近端/远端复合肌肉动作电位振幅比率均>0.3。结论 术末面神经近端/远端复合肌肉动作电位振幅比率是判断术后面神经远期功能,特别是肿瘤侵犯段功能的重要指标,为术中直接修复面神经提供了指导依据。     

术中电生理检测在肘管综合征的应用

目的 :探讨术中电生理监测在肘管综合征手术中的临床应用价值。方法 :对25例肘管综合征手术患者进行尺神经松解前后的电生理术中监测。结果 :术中尺神经肘管松解前后 ,传导速度提高50% ,潜伏期缩短30%,其中传导速度的改善有显著意义(P<0.05)。结论 :传导速度是较敏感的术中监测参数。肘管综合征术中应用电生理检测有一定临床意义。     

双源CT低剂量前瞻性心电触发序列扫描在冠状动脉血管成像的应用

Objective To evaluate low-dose CT coronary angiography with prospective electrocardiogram (ECG)-triggering using dual-source CT scanner.Methods Sixty-eight patients who underwent coronary CT angiography using a dual-source CT scanner were divided into 2 groups: group A (38 cases) and group B (30 cases).Prospective ECG-triggering sequence scan mode was employed for group A.Inclusion criteria included: heart rate <70 bpm, sinus rhythm, and heart rate fluctuation less than 10 bpm.Data acquisition was set at 70% of the RR-interval.Retrospective ECG-gating helical scan was performed for group B.Inclusion criteria included heart rates < 70 bpm and sinus rhythm.The exclusion criteria included heart failure and serious arrhythmias.In both groups, patients with a BMI≥24 kg/m2 were examined with a tube voltage of 120 kV, whereas patients with a BMI <24 kg/m2 were examined with a tube voltage of 100 kV.All images were transferred to a workstation for further processing and analysis.The imaging quality was evaluated.The imaging quality of coronary artery segments were compared with rank sum test between the two groups, and the radiation dose were compared with t test.Results A total of 476 coronary artery segments were evaluated in group A and 372 segments were evaluated in group B.The mean score of imaging quality for coronary artery segments in group A was 3.48±0.59 and that in group B was 3.53±0.58.There was no statistical difference in imaging quality between the two groups (Z=-1.432, P=0.187).The effective dose was on average (2.51±0.54) mSv (range 1.3--3.3 mSv) in group A, whereas on average (14.55±3.54) rosy (range 7.1--20.2 mSv) in group B.There was a statistical difference between the two groups (t=18.484, P=0.000).Conclusions Low-dose prospective ECG-triggering sequence scan in dual-source CT coronary angiography is feasible in patients with low heart rate and regular cardiac rhythm.This scan mode can substantially reduce radiation doses while preserving good diagnostic image quality.     

Identifying the affected hemisphere by 1H-MR spectroscopy in patients with temporal lobe epilepsy and no pathological findings in high resolution MRI

Up to 30% of patients with temporal lobe epilepsy (TLE) remain without remarkable changes in MRI. In this study we investigated the role of (1)H-MR spectroscopy ((1)H-MRS) in lateralizing the affected hemisphere in the mentioned patient group. Twenty-two consecutive patients diagnosed with TLE were investigated by high resolution MRI and (1)H-MRS. We examined the incidence and diagnostic accuracy of temporal metabolite alterations determined by Linear Combination of Model Spectra (L C Model) via water reference. Metabolite values of each hemisphere of TLE patients were compared with healthy controls. Results of metabolite alterations were related to intensive video EEG focus localization. Reduction of N-acetylaspartate + N-acetylaspartyl-glutamate (tNAA) in the affected hemisphere revealed identification in six of nine patients (66%) with unilateral TLE. Group comparison revealed a significant reduction of tNAA (6.1+/-0.8*) in the involved temporal lobe compared with controls (6.67+/-0.4*, P=0.026). Choline levels were significantly increased in the affected hemisphere (1.42+/-0.17*) compared with healthy controls (1.22+/-0.17*, P=0.035). The results of our study show that (1)H-MRS is able to identify the affected hemisphere of MRI negative TLE patients and can be used as an additive tool in multimodal focus localization.     

全雄激素阻断治疗晚期前列腺癌

为了评价全雄激素阻断治疗晚期前列腺癌的疗效，采用双侧睾丸切除、Ｆｌｕｔａｍｉｄｅ和Ｆｉｎａｓｔｅｒｉｄ联合治疗Ｄ２期前列腺癌病人５例。随访１５～２０个月，结果ＰＳＡ均正常，前列腺体积缩小６１．２％～６９．３％，有显著性差异（Ｐ＜０．０１），骨转移灶缩小、部分消失，积水肾脏完全恢复正常，所有病人治疗后全部有效。表明全雄激素阻断对晚期前列腺癌有良好的治疗效果。提出在三个层次上阻断雄激素治疗晚期前列腺癌的策略。     

Five-Year Outcome After Epilepsy Surgery in Nonmonitored and Monitored Surgical Candidates

Summary: Purpose : We wished to compare outcome 5 years after temporal lobectomy in 28 patients selected for surgery on the basis of interictal EEG patterns with that in 46 patients who underwent EEG-video monitoring studies as part of their preoperative evaluation during the same era.
Methods : The 28 nonmonitored patients had interictal EEG patterns that demonstrated a consistent, unilateral, anterior-midtemporal epileptiform focus, without discordant findings from other studies. Outcomes were assessed for years 4 and 5 after operation.
Results : Twenty-six of 28 (92.9%) nonmonitored patients were seizure-free or had at least 75% reduction in seizures. Twenty-nine of 46 (63.0%) monitored patients were seizure-free or had at least 75% reduction in seizures. Preoperative interictal EEGs of 29 of these patients showed independently localized bitemporal, ex-tratemporal, midposterior temporal, or diffuse epileptiform patterns. The remaining 17 monitored patients had preoperative strictly unilateral anterior-midtemporal interictal discharges, and their outcome was comparable to the nonmonitored group, with 15 (88.8%) seizure-free or with at least 75% reduction in seizures.
Conclusions : A proportion of candidates for epilepsy surgery can be selected without ictal recordings provided that interictal EEGs demonstrate consistent unilateral anterior-midtemporal epileptiform discharges and that other data are not discordant.     

Airborne emissions at skin surfaces: a potential biological exposure index

 Dermal exposures of methanol were administered in a clinical study designed to compare several biological indicators. Four subjects were exposed in five exposure sessions of varying length. In each session, a sequence of measurements of methanol concentrations in blood, breath, and headspace samples of air at exposed and unexposed skin were collected before and after dermal exposures. Skin headspace samples, collected in gas sampling bags, were designed to reflect equilibrium skin: air partitioning. At exposed skin, headspace samples were highly elevated for at least 8 h following exposure, indicating the presence of a methanol reservoir in skin. After exposure, methanol concentrations at exposed skin showed a rapid initial decline, then a slower first-order decrease. Methanol concentrations were clearly detectable in headspace samples at unexposed skin. Substantial transfer from exposed skin occurred due to mechanical contact and washing. When transfer was restricted, surface concentrations at unexposed skin were similar to levels in breath and were strongly correlated to methanol concentrations in blood. While results are preliminary due to the small sample sizes and several unresolved experimental issues, the simple, rapid, and noninvasive skin headspace measurements appear useful as a biological exposure indicator that clearly shows the presence and site of a dermal exposure, and measurements at unexposed skin reflect concentrations in blood. Received: 14 March 1995/Accepted: 3 November 1995