Tissue response to bioabsorbable self-reinforced polylevolactide and polyglycolide pins implanted intra-articularly and directly into the bone on different levels

Self-reinforced poly-l-lactide (SR-PLLA) and self-reinforced polyglycolide (SR-PGA) pins were implanted intra-articularly and directly into the bone of the distal femur of rats at three levels: above, on the same level, and under the surface. For the controls only channels were drilled, or the controls were not operated at all. The follow-up times were 3, 6, and 12 weeks for SR-PGA and 3, 6, 12, and 24 weeks for SR-PLLA. The macroscopic appearance and histologically the villus reaction, the mononuclear phagocytosis and giant cells, the neutrophils, the lymphocytes, the plasma cells, the eosinophils, and the mast cells were analyzed. In the histologic analysis, the most favorable implantation depth was found to be under the surface where the contact between the implants and bone was best, and the orifice was covered with new trabecular bone at 3 weeks. This was especially seen in intra-articular implantation. In general, the tissue responses were mild, and could also be explained in the statistical analysis by a normal postoperative tissue response and faster biodegradation of PGA. Received: 21 August 1997     

Forehead lifting: state of the art

Forehead lifting serves to restore a more youthful appearance as well as a more functional and aesthetically pleasing brow position. The purpose of this review is to describe the pertinent anatomy and forehead aesthetics, then to discuss the patient evaluation, surgical approaches, complications, and nonsurgical adjuncts. Anatomic features reviewed include the layers of the forehead and scalp, blood supply, innervation, musculature, and the temporal branch of the facial nerve anatomy. Forehead aesthetics described include the aging process, with its contributing factors and consequences, and the ideal brow position in women and men. Key aspects of the patient evaluation include assessment of skin type; ptosis; hairline, brow, and lid position; symmetry; and bony contours. Pertinent past medical/surgical history as well as family history are reviewed, and the need for ophthalmology evaluation is discussed. Surgical indications and approaches, including direct, coronal, mid-forehead, endoscopic, and trans-blepharoplasty, are reviewed. The advantages and disadvantages of each approach are discussed and techniques briefly described. Complications are mentioned, and the article concludes with a review of nonsurgical adjuncts.     

Phytoplankton abundance, dominance and coexistence in an eutrophic reservoir in the state of Pernambuco, Northeast Brazil

The present study reports the phytoplankton abundance, dominance and co-existence relationships in the eutrophic Carpina reservoir, Pernambuco, Brazil. Sampling was carried out at six different depths bimonthly at a single reservoir spanning two climatic periods: dry season (January, September, and November 2006) and rainy season (March, May, and July 2006). Density, abundance, dominance, specific diversity and equitability of the community were determined, along with chlorophyll a, and physical and chemical variables of the environment. Eight species were considered abundant, and their densities corresponded to more than 90% of the total phytoplankton community quantified. Cyanobacteria represented more than 80% of this density. Cylindrospermopsis raciborskii was the only dominant taxon in the dry season, and was co-dominant in the rainy season. C. raciborskii, Planktothrix agardhii and Geitlerinema amphibium had the greatest densities and lowest vertical variation coefficients. The statistical analysis indicated relationships with vertical and seasonal variations in the phytoplankton community and the following variables: total dissolved solids, water temperature, electrical conductivity and pH. The changes in the environmental variables were discrete and regulated by the establishment of precipitation however, they were able to promote vertical and seasonal instability in the structure of the phytoplankton community.     

异体手移植的手术设计与操作

目的 探讨异体手移植的手术设计与技术操作要点。方法 2例右手缺失病人行异体手移植,参照自体断腕再植的基本程序,依次受区准备、供手准备、移植手组织重建。骨骼再接平面位于桡尺骨离桡骨关节面2.5cm～3cm处,桡骨阶梯状截骨、螺钉固定,尺骨平面截骨、三棱针或钢板内固定;先缝合屈侧深肌腱,吻合尺、桡动脉后静脉放血,再吻合头、贵要静脉,缝合屈侧浅肌腱及伸侧肌腱,吻合神经,缝合皮肤。术后抗免疫排斥、抗感染、抗凝、抗血管痉挛。结果 手术时间分别为7h52min、9h10min,供手缺血时间6h、ah 19min。病例一移植手血循环良好;病例二术后3小时静脉危象,经手术恢复血循环。现术后8个月移植手存活良好,无免疫排斥反应发生,手握持功能及手部感觉已恢复,手内在肌功能部分恢复。结论 异体手移植的手术设计重点依据手缺失残端位置确定受一供体手移植平面,组织重建的顺序为骨骼、深肌腱、动脉、静脉、浅肌腱、神经和皮肤。     

双能X线骨密度仪精密度和准确度的研究

目的：通过测量长、短期精密度和短期准确度对双能X线吸收法（ dual－energy X－ray absorptiometry ,DXA）骨密度仪进行质量控制。方法①长期精密度：对质量保证（Quality Assurance,QA）模块连续1年的测试数据进行统计分析,分别计算其高、中、低骨密度、均值骨密度、骨矿盐含量、投影面积的变异系数（ coefficient of variation ,CV）;②短期精密度：取连续25天的QA模块测试数据,计算高、中、低骨密度平均值和标准差（standard deviation,SD）,制作Shewhart质控图。另外选取30名志愿者,分别测量L1－4椎体,双侧股骨颈、大粗隆、Ward＇s三角、全髋关节的骨密度（bone mineral density,BMD）值,计算均方根变异系数（ root mean square of the CV ,RMS－CV）;③短期准确度：取连续25天的QA模块测试数据,计算高、中、低骨密度的准确度。结果①长期精密度：QA模块测量高、中、低骨密度、均值骨密度、骨矿盐含量、投影面积的CV分别为0．37％、0．37％、0．41％、0．43％、0．47％、0．12％;②短期精密度：连续25天QA模块测试数据均符合Shewhart 法则;30例受试者L1－4椎体,双侧股骨颈、大粗隆、Ward＇s 三角、全髋关节各测量部位的RMS－CV 分别为1．3％、0．8％、0．9％、1．2％、1．3％、1．5％、1．6％、0．6％、0．6％;③短期准确度：连续25天QA模块测试数据的高、中、低骨密度的准确度分别为－0．07％、0．10％、0．60％。结论进行长、短期精密度和准确度测试能反映双能X线吸收骨密度仪的一致性和可靠性,可有效提高骨质疏松的流行病学研究、诊断、治疗、药物试验研究的可信度。     

Enteral nutrition in HPB surgery: past and future

Perioperative nutrition has, during the past century, been transformed from a tool to provide calorie and nitrogen support to a tool to boost the immune system and increase resistance to complications. Despite all the progress in medicine and surgery, perioperative morbidity, the rate of infections, thrombosis, and the development of serosal adhesions has remained the same as long as can be judged, or at least during the past 80 years. Most prone to develop complications are persons above the age of 65 and persons with depressed immunity. About 80% of the immune system is localized in the gastrointestinal tract, which offers great opportunities for modulation through enteral nutrition. As the stomach has a tendency to develop postoperative paralysis, tube feeding is often necessary. In 1918, Andresen demonstrated the advantages of enteral nutrition, which already started on the operating table. Mulholland and colleagues and Rhoads and co-workers demonstrated, during the 1940s, certain advantages of enteral tube feeding. Also, the works by Alexander, Fischer, and Ryan, and their co-workers supported the value of early enteral feeding, and suggested enteral feeding as an effective tool to boost the immune system. It was, however, works published in the early 1990s, by Moore and colleagues and by Kudsk and colleagues, which made surgeons more aware of the advantages of early enteral nutrition. Surgery in the hepatobiliary pancreatic field is known to have a high rate of complications. Uninterrupted perioperative nutrition, i.e., nutrition during the night before, during surgery, and immediately after, offers a strong tool to prevent complications. It is essential that the nutrition also provides food for the colon, e.g., fiber and healthy bacteria (probiotics) to ferment the fiber and boost the immune system. Received: February 19, 2002 / Accepted: March 8, 2002 Offprint requests to: S. Bengmark     

The brain: functional divisions

The incompletely separated cerebral hemispheres consist of a thin outer folded cortex of grey matter containing organized neuronal cell bodies and interneurons. Some of the surface convolutions subserve particular sensory or motor functions. Incoming afferent and projected efferent fibres constitute the underlying white matter, which connects different parts of each hemisphere, the hemispheres to each other and (as the corona radiata) to subcortical nuclei, especially components of the deeply-embedded diencephalon and the basal ganglia, and continuing between the latter as the internal capsule to and from the cerebellum and brainstem. Divisions of the diencephalon, the deeper part of the embryonic forebrain, include the epithalamus (pineal gland), the thalamus (connected extensively with the cortex), the subthalamus and the hypothalamus (involved in the autonomic nervous system, limbic system and neuro-endocrine system). The brainstem, consisting of the midbrain, pons and medulla, allows passage of many ascending and descending nerve fibre tracts between the brain and spinal cord, carrying sensory information from and allowing movement of the limbs and trunk. It is also the site of many of the cranial nerve nuclei, through which the brain innervates the head region. It houses the centres controlling vital aspects related to respiration, cardiovascular function and consciousness levels. The cerebellum also has a cortex of grey matter, tightly convoluted into folia, and containing layered neuronal cell bodies projecting laterally and, as underlying white matter, to a collection of deep nuclei. Fibres run to and from the cerebellar nuclei in a series of peduncles to the midbrain, pons and medulla, and allow the cerebellum to coordinate movement at an unconscious level.     

糖尿病合并骨质疏松的中医研究进展

随着全球老龄化进程，糖尿病合并骨质疏松在慢性疾病中发病率显著升高，其最常见的并发症之一骨折严重降低患者生活质量。现代医学治疗具有经济负担重、缺少前瞻性研究的缺点，而中医药治疗具有不良反应小、依从性高及价格适中等优点，具有临床多途径、多靶点治疗糖尿病合并骨质疏松的独特优势。近年来中医药有关其研究越来越多，在治疗上注重滋补肝肾，重视补阴药及活血药的运用，许多研究者结合现代医学的检验、检查指标证明了中药的疗效，而从单味药、药对或是复方着手的许多实验研究又证明其疗效通路机制，除此之外，针灸推拿等中医特色治疗也有改善糖代谢及骨代谢的作用。笔者从糖尿病合并骨质疏松的病因病机、辩证分析、治法、实验研究、临床研究及中医特色疗法等方面进行综合论述，深入认识糖尿病合并骨质疏松，能为其治疗提供一定的理论依据及临床参考。     

Temporal and spatial changes in element distribution in bone and cartilage

Background  Bone and cartilage act as reservoirs for a number of elements, and the perturbation of these elements is suggested to contribute to various diseases. Even so, little is known about their respective temporal and spatial distribution. Methods  Three knee joints of three mice on the first day after birth, three knee joints of 3-week-old mice, and three knee joints of 20-week-old mice were prepared. We performed element mapping in the bone and cartilage of normal mouse knee joints. We measured element distribution in articular cartilage, trabecular bone, cortical bone, joint cartilage, growth plates, and joint cavities using energy dispersive X-ray spectrometry. Results  The analysis revealed the following: (1) The main elements in articular cartilage of 1-day-old mice were Na, O, P, S, and Ca; and those in bone were Na, O, P, S, K, Ca, and Mg. (2) The main elements in the growth plate of 3-week-old mice were Na, N, O, P, S, Cl, K, and Ca; those in joint cartilage were Na, O, P, S, Cl, and K; and those in bone were Na, O, P, Ca, and Mg. (3) The main elements in the growth plate of 20-week-old mice were Na, O, P, S, Cl, K, and Ca; and those in bone were Na, O, P, S, K, Ca, and Mg. After corrections were made for the Na ratios of these elements, we investigated the temporal and spatial changes in the distribution of each element. On the first day after birth, a spatial change was seen in the growth plate cartilage: the more the cartilage matured toward hypertrophy, the more S and Ca it contained. Temporal changes in element distribution in the growth plate cartilage, articular cartilage, and bone were observed. Growth plate cartilage of the older mice contained more S and Ca than that of the younger mice. Bone of the older mice contained more Ca and Mg than that of the younger mice. Spatial changes in element distribution in the cortical bone were also seen; that is, the more the cortical bone matured toward diaphysis, the more Mg and the less S it contained. In contrast, no temporal or spatial changes in element distribution were observed in the joint space. No significant temporal or spatial changes in the distribution of P, Cl, or K were seen. Conclusions  These results suggest that element mapping may be useful for identifying the age and maturity of different skeletal tissues. In particular, it may help distinguish between immature cartilage and mature cartilage based on the Ca and S contents.     

From the lumen to the laparoscope

Throughout the ages, the issues that have defined the management of disease processes have been particularly exemplified in the gastrointestinal tract. The use of gas lamps and candles with reflectors by Bozzini, Segalas, Cruise, and Fisher (19th century) allowed for some ingress into both the upper and lower gastrointestinal tract. Von Mikulicz, Leiter, Nitze, Kelling, and Jacobaeus contributed to the development of rigid instruments that could be used endoscopically or laparoscopically. Endoscopic efforts were amplified and extended by Rosenheim, Sternberg, Wolf, and, finally, Schindler, who not only introduced novel lens systems but also for the most part overcame the problems of flexibility and illumination. Bernheim, Ruddock, Veress, and Palmer made significant technical and clinical contributions to abdominal cavity exploration. The subsequent application of Hopkins and Kapany's work on optics, and the development by Hirschowitz and Curtiss of the flexible fiber optic endoscope, enabled the design of instruments that would allow the appropriate illumination and vision of both the farthest reaches of the bowel as well as the interior of the abdomen. Thus, the same endoscopic instruments coupled with a surgical interest in diagnostic laparotomy allowed for the evolution of minimally invasive surgery along a similar timescale. The cycle whereby diagnostic laparotomy in the early part of the century was supplanted by endoscopy and laparoscopy has now attained full circle whereby laparoscopy has evolved from a diagnostic procedure into one with major therapeutic applications and is perceived as the state-of-the-art technique for a wide variety of operations, including appendectomy, cholecystectomy, hernia repair, fundoplication, splenectomy, colectomy, and gastrointestinal anastomoses.     

围绝经期女性骨密度特点分析

目的总结并分析围绝经期女性腰椎1-4、股骨颈及髋关节部位的骨密度(bone mineral density,BMD)及其临床特点。方法收集2017年12月至2018年6月在我院住院部住院并进行双能X线吸收法骨密度检测的183例围绝经期女性,分别测定其腰椎1-4总体BMD、左侧股骨颈及左髋关节全部BMD,同时分析比较年龄、体质量指数(body mass index,BMI)与骨质疏松的关系。结果 183例患者中,检出骨质疏松39例(21. 3%),其中腰椎1-4、左股骨颈和左髋关节BMD各检出骨质疏松33例(18. 0%)、20例(10. 9%)、13例(7. 1%)。腰椎总体骨质情况与股骨颈、髋关节检查结果相符的各有129例(70. 5%)、119例(65. 0%),股骨颈总体骨质情况与髋关节检查结果相符的有137例(74. 9%)。在骨质疏松组、骨量减少组和骨量正常组,同一组病人腰椎1-4骨密度左髋关节骨密度左侧股骨颈骨密度,组间差异均有统计学意义。年龄、BMI与骨质疏松的发生均相关。骨质疏松与年龄呈正相关,与BMI、腰椎1-4总BMD、左股骨颈BMD、左髋关节BMD负相关,腰椎1-4 BMD与骨质疏松相关程度最高。结论腰椎整体骨密度呈现虚假升高趋势,腰椎1-4 BMD诊断骨质疏松的敏感性和特异性分别为84. 6%、100%,股骨颈分别为51. 3%、100%,髋关节分别为33. 3%、100%;年龄增长、BMI偏低会增加围绝经期妇女罹患骨质疏松的风险。     

Melanoma of palms, soles, and nail-beds.

The clinical and histological characteristics of palmar, plantar, and subungual melanomas treated in the division of plastic surgery of Helsinki University Hospital between 1970 and 1984 were analysed. The peak incidence was during the seventh decade of life, and the mean delay between the onset of symptoms and the diagnosis was one year. The delay was as much the fault of the physician as of the patient. The observed and relative five-year-survival rates for all 31 patients were 60% and 67%, and the 10-year-survival rates 39% and 49%, respectively. There were 15 cases of the acral lentiginous subtype, and the observed and relative five-year-survival rates were 65% and 71%, and the 10-year-survival rates 48% and 64%, respectively. For the nodular melanomas (n = 11) the survival rates were 53% and 60%, and 39% and 53%, respectively. For the three superficial spreading melanomas they were 50% and 52%, and 25% and 28%, respectively. Microstaging criteria (Breslow and Clark) were both good prognostic indicators. The series was too small for multivariate analysis.     

The haemodynamics of human septic shock

In the time it has taken medicine to develop the techniques to describe the circulatory changes of severe infections, both pattern and process have been profoundly influenced by the use of intravenous fluids, vasopressors, antibiotics, steroids, mechanical ventilation and haemoflltration. Constant features of severe sepsis include a reduction in peripheral vascular tone on both the arterial and venous sides of the circulation, a defect in oxygen utilisation resulting in lactic acidosis, and varying degrees of myocardial dysfunction. These events have a temporal progression, the precise pattern observed depending on the tempo of the infection, the influence of therapeutic manoeuvres, the age and comorbidities of the patient, and the time the observations are made in the course of events. Early sepsis is accompanied by a decrease in systemic vascular resistance and a metabolic acidosis. The clinical picture includes fever, tachycardia, tachypnoea, respiratory alkalosis and an increased cardiac output with warm, dry peripheries and a bounding pulse. Advanced sepsis involves varying degrees of venous and myocardial contractile failure, and is characterised by progressive acidaemia, respiratory failure and marked sympathetic adrenergic activation. In the absence of vigorous fluid resuscitation, the cardiac output is decreased and the patients are cold, clammy peripherally shut down, and frequently confused, obtunded or comatose. In infections with a silent primary focus (predominantly involving Gram-negative organisms), this stage is frequently the first to attract the attention of attending staff. Late sepsis is characterised by profound acidaemia, vascular hypo-responsiveness, multiple organ failure and death.     

肠道菌群与胆石症病因的研究进展

胆石症是最常见的胆道外科疾病,临床症状主要取决于结石的部位、胆道梗阻、胆道感染等因素,具体可表现为腹痛、发热、恶心、呕吐、黄疸等症状。随着人口的老龄化、膳食结构的改变,其发病率呈逐渐上升趋势。目前虽然诊断及治疗技术已相对成熟,但胆道结石形成的具体病因及发病机制尚未完全阐明。代谢综合征相关疾病可能与胆石症的形成与发展存在密切关系。肠道菌群失调可能会引起代谢变化,导致代谢相关疾病的发生发展,因此胆石症的发生与肠道微生态失衡存在密切的关系,但有关肠道微生态失衡与胆石症发生的关系研究相对较少,其作用机制也不甚清楚。笔者综述肠道菌群在胆石症形成的发病机制中的作用,探讨未来的研究方向。     

Tie2 ligands angiopoietin-1 and angiopoietin-2 are coexpressed with vascular endothelial cell growth factor in growing human bone

Angiogenesis is essential for bone growth and repair. Recent studies have shown that the endothelial-specific mitogen vascular endothelial growth factor (VEGF) is a key regulator of vascular invasion into the growth plate in infant and adolescent animals. In order to identify mechanisms regulating VEGF-induced angiogenesis in growing bone, we have investigated the expression of the angiopoietins (Ang-1 and Ang-2) in human neonatal ribs. Ang-1 and Ang-2 exhibited similar patterns of staining in the growing rib. In the cartilage, expression of Ang-1 and Ang-2 increased with chondrocyte maturation. Ang-1, Ang-2, and VEGF were not detected in the resting zone except adjacent to vascular canals, and maximum expression was detected at the cartilage bone interface. In the cartilage, Ang-2 was more highly expressed than Ang-1 or VEGF, with staining observed in the proliferating, hypertrophic, and mineralized zones. In the bone, Ang-1, Ang-2, and VEGF were detected in modeling and remodeling sites. Ang-1 was detected in the majority of osteoblasts, osteoclasts, and in some marrow space cells. Ang-2 was expressed at variable levels by osteoblasts and osteoclasts in modeling and remodeling bone. VEGF was detected in cells at bone surfaces and in the marrow spaces. Strong staining for VEGF was observed in osteoblasts and osteoclasts in modeling and remodeling bone. In the perichondrium, Ang-1, Ang-2, and VEGF were most highly expressed adjacent to the hypertrophic zone and at sites of bone collar formation. In the periosteum, Ang-1, Ang-2, and VEGF expression colocalized with alkaline phosphatase expression. These observations provide the first evidence for the expression of the angiopoietins in growing human bone in vivo. The distribution of Ang-1, Ang-2, and VEGF indicate these factors may play key roles in the regulation of angiogenesis at sites of endochondral ossification, intramembranous ossification, and bone turnover in the growing human skeleton.     

基于文献计量学分析太极拳防治骨质疏松研究现状

目的探究太极拳防治骨质疏松的现状及未来发展趋势,从而为进一步研究提供参考依据。方法检索所有公开发表的关于太极拳防治骨质疏松的文献,分析文献年代分布、文献类型和语言、期刊分布、核心机构、高频关键词、疗效指标等特点。结果纳入文献共210篇,近10年共发表136篇论文,占全部论文量的64.76%,是太极拳防治骨质疏松研究的热点时期,论文数量总体呈逐年上升趋势;文献以中文期刊类临床研究论文为主,中文期刊中,《中国骨质疏松杂志》和《中国老年学杂志》的载文量最高;太极拳、骨密度、老年人、女性等为出现频率最高的关键词;骨密度、平衡能力、骨代谢指标为太极拳防治骨质疏松的常用评价指标。结论近10年为太极拳防治骨质疏松研究的热点时期,目前研究集中在中美两国,研究类型以临床研究为主。现代证据表明太极拳防治骨质疏松疗效确切,但结局指标缺乏规范,仍待更深层次的理论挖掘与更高水平的临床证据支持。     

跟骨内外侧经皮置针安全区解剖学研究

目的 划定国人跟骨内、外侧外固定针进针位置解剖学相对安全区.方法 解剖14具正常成年人足踝部标本.于跟骨内侧取跟骨最内下后点为A点,内踝最下点为B点,足舟骨结节为C点.解剖出跟骨内侧神经、足底外侧神经最后分支、足底外侧神经、足底内侧神经、胫后动脉、足底外侧动脉和足底内侧动脉.根据各结构行经AB、AC线的位置,确定跟骨内侧的相对安全区;于跟骨外侧取跟骨最外下后点为D点,外踝最下点为E点,解剖出跟骨外侧神经、腓肠神经、小隐静脉主干,同理确定跟骨外侧的相对安全区.结果 跟骨内侧神经、足底外侧神经最后分支、足底外侧神经、足底内侧神经、胫后动脉分别行经AB线后下22%、50%、56%、64%及58%处,跟骨内侧神经、足底外侧神经最后分支、足底外侧神经、足底内侧神经、足底外侧动脉、足底内侧动脉分别行经AC线后下14%、39%、49%、63%、41%及57%处.跟骨外侧神经、腓肠神经、小隐静脉分别行经DE线后下 19%、65%及61%处.结论 在跟骨内侧,AB线后1/2、AC线后1/3所在圆形区域为经皮置针相对安全区.在跟骨外侧,经DE线中点垂线后方的跟骨为经皮穿针相对安全区.     

Endovascular restorative neurosurgery: a novel concept for molecular and cellular therapy of the nervous system

The amalgam of molecular biology and neurosurgery offers immense promise for neurorestoration and the management of neurodegenerative deficiencies, developmental disorders, neoplasms, stroke, and trauma. This article summarizes present strategies for and impediments to gene therapy and stem cell therapy of the central nervous system and advances the concept of a potential new approach, namely endovascular restorative neurosurgery. The objectives of gene transfer to the central nervous system are efficient transfection of host cells, selective sustained expression of the transgene, and lack of toxicity or immune excitation. The requisite elements of this process are the identification of candidate diseases, the construction of vehicles for gene transfer, regulated expression, and physical delivery. In the selection of target disorders, the underlying genetic events to be overcome, as well as their spatial and temporal distributions, must be considered. These factors determine the requirements for the physical dispersal of the transgene, the duration of transgene expression, and the quantity of transgene product needed to abrogate the disease phenotype. Vehicles for conveying the transgene to the central nervous system include viral vectors (retroviruses, lentiviruses, adenoviruses, adeno-associated viruses, and herpes simplex virus), liposomes, and genetically engineered cells, including neural stem cells. Delivery of the transgene into the brain presents several challenges, including limited and potentially risky access through the cranium, sensitivity to volumetric changes, restricted diffusion, and the blood-brain barrier. Genetic or cellular therapeutic agents may be injected directly into the brain parenchyma (via stereotaxy or craniotomy), into the cerebrospinal fluid (in the ventricles or cisterns), or into the bloodstream (intravenously or intra-arterially). The advantages of the endovascular route include the potential for widespread distribution, the ability to deliver large volumes, limited perturbation of neural tissue, and the feasibility of repeated administration.