生理参数及药物注射方式对球形实体肿瘤中药物输运的影响

目的　研究球形实体肿瘤中生理参数对药物输运的影响，以及探讨有较好效果的药物注射方式。方法　设肿瘤中毛细血管网成球对称分布，肿瘤中的毛细血管表面积和肿瘤体积之比为半径的函数。肿瘤间质为多孔介质，化学药物透过毛细血管壁进入肿瘤间质，在肿瘤间质中输运满足扩散方程。肿瘤外正常组织富含血管和淋巴，药物能被淋巴管吸收，药物输运采用改进的药代动力学模型。用肿瘤中各部位药物浓度维持在最小药物浓度MEC水平以上的时间曲线面积(AUC)来衡量药物的效果。结果　增大肿瘤间质中毛细血管对药物的通透性P，提高药物在肿瘤间质的扩散系数D，AUC的值均增大。在给出的六种给药方式中，分时段连续滴注和等时间间隔一次性注射的给药方式，它们的AUC值最大。结论　增大肿瘤间质中毛细血管对药物的通透性，提高药物在肿瘤间质的扩散系数，以及采用分时段连续滴注和等时间间隔一次性注射的给药方式，有利于肿瘤的治疗。     

实体肿瘤药物输运与给药方式的集中参数模型及实验研究

目的研究不同给药方式对实体肿瘤抗癌药物疗效的影响,并通过动物实验验证。方法分别建立体内药代动力学和肿瘤内药物输运的集中参数模型,模拟单次快速注射和等时间间隔三次快速注射时肿瘤间质组织药物浓度Ct随时间的变化。实验小鼠分为两组,分别进行抗癌药羟基喜树碱(HCPT)单次快速注射和等时间间隔3次快速注射,观察其肿瘤内药物平均浓度。对数值模拟结果和动物实验结果进行比较。结果数值模拟结果显示,对于相同总量药物,等量等间隔的三次给药,肿瘤间质组织药物浓度Ct高于单次给药。动物实验的实测结果相同。结论3次给药的效果显著优于单次给药。集中参数模型基本能够定量反映不同给药方式的效果。     

青光眼小梁切除术后并发浅前房原因分析及护理对策

目的讨论青光眼小梁切除术后浅前房的预防和护理方法.方法总结36例(36眼)青光眼小梁切除术浅前房病人心理、生活、药物护理要点,分析浅前房的发生原因及护理对策.结果通过实施有效的治疗和护理,3○眼前房恢复理想深度,5眼经药物及手术治疗前房恢复并稳定,1眼呈间歇性浅Ⅰ度,持续给阿托品滴眼前房恢复.结论及时给予术后正确的护理指导可避免部分病人浅前房发生,正确有效的护理对前房深度恢复稳定及避免并发症的发生有重要意义.     

血流限速生理药动学模型的平均稳态浓度

对血流限速生理药动学模型，本文研究表明，多次给药后，该模型一任一器官组织的平均稳态浓度可用一次给药后药─时曲线下的面积ＡＵＣ与给药问隔时间τ之比来估计；给出了为获得预期的平均稳态浓度，如何确定给药间隔时间、维持剂量以及负荷剂量的方法；消除撂官的清除率可用平均稳态浓度来定义。     

注射方式对二维实体肿瘤中药物输运影响的数值研究

目的研究药物注射方式对二维实体肿瘤中药物输运的影响,确定较适当的注射方式。方法根据数值生成的肿瘤二维血管网,研究药物的输运。采用肿瘤中各部位药物浓度维持在最小药物浓度MEC水平以上的时间曲面下体积VUS来衡量药物的效果。对不同的施药注射方式进行了探讨。结果MEC较小时各种注射方式效果接近;MEC较大时,比较适合采用短时间集中注射方式。结论对肿瘤进行药物注射策略选取时,应根据肿瘤具体特性,以及药物施加方式对肿瘤细胞产生的不同作用来组合设计相应的优化施药方案。     

不同眼球按摩方式对青光眼小梁切除术后患者影响效果探析

目的:探究不同眼球按摩方式干预青光眼小梁切除术后患者对其功能性滤过泡形成情况、眼压控制及视力变化的影响.方法:选取我科2018年2月至2020年10月期间81例青光眼小梁切除术后患者,随机分组.对照组40例在常规干预基础上联合家属眼球按摩方式干预,观察组41例应用常规干预结合自行眼球按摩干预,观察两组患者眼压控制情况,功能性滤过泡形成情况,疼痛反应,并发症发生情况.结果:干预6 m后,观察组患者眼压水平、黄斑水肿、前房出血、低眼压发生率均显著低于对照组(P<0.05),视力增加≥0.2例数显著高于对照组(P<0.05);手术成功率、功能型滤过泡形成率高于对照组,且差异有统计学意义(P<0.05).结论:青光眼小梁切除术后患者经自行眼球按摩结合常规干预,可控制患者眼压水平,提高功能性滤过泡生成率,提升视力增加0.2发生率,提高手术成功率,降低并发症.     

46例外伤性前房积血的临床护理

外伤性前房积血是眼科临床上常见的急诊外伤之一，前房积血多见于眼球钝挫伤，是眼外伤引起的常见疾病。其预后与出血量的多少、出血部位、就诊时间、治疗是否及时、恰当、合理以及有无继发出血等并发症及其严重程度有密切关系。少量积血可以很快吸收，视力往往不受影响，但严重的前房积血可引起继发青光眼及角膜血染等并发症而造成视功能损害，导致视力下降甚至失明[1]。因此正确及时的治疗尤为重要。     

超声联合微泡介导肿瘤药物治疗的研究进展

目前肿瘤的治疗方式包括手术治疗、放疗、化疗、基因治疗、免疫治疗和中医中药治疗等,化疗是其中一种极其重要的治疗方式。然而,无论口服还是静脉等给药方式,化疗药物进入血液循环后导致药物利用率低、不良反应明显。超声联合微泡介导药物释放是一种有效的非侵入性、靶向给药传递技术,在超声波脉冲驱动下,微泡以每秒几十到几百米的速度振荡,...     

手术治疗恶性青光眼的疗效分析

目的探讨恶性青光眼经药物治疗无效后手术治疗的效果。方法回顾性分析我院9例恶性青光眼病例,所有病例经药物治疗无效后均采取手术治疗,方法包括单纯经睫状体扁平部玻璃体腔穿刺抽液或联合前房重建术,1例采取晶状体联合前部玻璃体切除术。结果术后随访1～6个月,术后眼压12.2～18.6 mmHg,平均15.5 mmHg,全部前房深度恢复且稳定,视力0.02～0.3。结论对药物治疗无效的恶性青光眼应及时采取手术治疗,单纯经睫状体扁平部玻璃体腔穿刺抽液术或联合前房重建术能有效缓解恶性青光眼,部分严重病例则需行晶状体联合前部玻璃体切除术。     

高眼压状态下青光眼手术的临床观察

目的探讨高眼压状态下青光眼手术方法的安全性和效果。方法对32例药物降压无效的青光眼患者进行青光眼手术,术后观察出血、滤过泡、前房、眼压及视力的变化。结果术后1月视力提高的21只眼(65.63%);保持不变的11只眼(34.38%);眼压术后≤21mmHg者28只眼(87.5%);用药物控制的4只眼(12.5%)。结论高眼压状态采取手术治疗是安全有效的。     

Numerical Simulations of Ethacrynic Acid Transport from Precorneal Region to Trabecular Meshwork

Topical application of drugs for treatment of intraocular diseases is often limited by inadequate transport and induced toxicity in corneal tissues. To improve the drug delivery, a mathematical model was developed to numerically simulate the transport process of ethacrynic acid (ECA), a potential drug for glaucoma treatment, in the anterior segment of a typical human eye. The model considered diffusion of ECA in all tissues and the aqueous humor (AH) as well as convection of ECA in the AH. The simulation results showed that ECA concentration in the eye depended on the rate of AH production, the half-life of ECA in the precorneal tear film, and the transport parameters in the model. In addition, the main pathway for ECA clearance from the eye was the trabecular meshwork (TM) and the rate of clearance was approximately proportional to the AH production rate. The model predicted that the most effective approach to improving topical drug delivery was to prolong its half-life in the precorneal tear film. These simulation results and model prediction, which could be verified experimentally, might be useful for improving delivery of ECA and other therapeutic agents to the TM as well as other tissues in the anterior segment of the eye.     

Ultrastructural alterations induced in quail ciliary neurons by postganglionic nerve crush and by Ricinus toxin administration, separately and in combination

The response to postganglionic nerve crush and Ricinus toxin administration by the ciliary neurons of the quail ciliary ganglion was investigated at the ultrastructural level. The toxin was either applied at the crush site on the postganglionic nerves or injected into the anterior eye chamber without any other operative intervention. Crush of postganglionic nerves without toxin administration and saline injection into the anterior eye chamber served as controls for the two toxin administration procedures. Postganglionic nerve crush caused a distinct chromatolytic reaction, accompanied by massive detachment of the preganglionic axon terminals from the ciliary neurons and loss of most of the synapses, both chemical and electrical. This process does not induce cell death and is reversible. Saline injection in the anterior eye chamber caused a moderate retrograde reaction in some of the ciliary neurons, presumably as a consequence of paracentesis. The changes consisted mainly of an increase of perikaryal neurofilaments with, at most, a minor detachment of the preganglionic boutons from a small portion of the cell body at the nuclear pole. Ricinus toxin administration induced neuronal degeneration following a pattern common to both delivery modes. The degenerative process consisted of disruption and detachment of polyribosomes from the rough endoplasmic reticulum, an increase of smooth cisterns and tubules, a dramatic increase of neurofilament bundles, compartmentalization of the cytoplasmic organelles and, finally, karyorrhexis and cell lysis. The final stages of Ricinus toxin degeneration involve a progressive accumulation of extracellular flocculo-filamentous material and cell lysis. After administration of Ricinus toxin to the crush site, ricin-affected neurons showed withdrawal of the preganglionic boutons from a portion of the ciliary neuron, especially at the nuclear pole. After Ricinus toxin injection into the anterior eye chamber, however, the bouton shell surrounding the affected ciliary neurons remained intact in the early stages of degeneration. Detachment of the preganglionic terminals and disruption of the cell junctions, therefore, is the consequence of nerve crush and not of the toxin itself.

This study demonstrates that quail ciliary neurons are a suitable model for experimental neuropathology and neurotoxicology.     

Measurement of amphotericin B concentration by resonant Raman spectroscopy--a novel technique that may be useful for non-invasive monitoring.

We wished to determine whether Resonant Raman Spectroscopy (RRS) could be used to measure Amphotericin B (AmB) at therapeutic and subtherapeutic concentrations in a model system mimicking the anterior chamber of the eye. The goal was to develop a technique for non-invasive measurement of AmB levels in the aqueous humor (AH) of the eye. A krypton-ion laser source (406.7 nm) was used for excitation and Resonant Raman Spectra were captured with a confocal system in an anterior chamber (AC) model. These spectra were used to develop a correlation curve for prediction of AmB levels. Subsequently, one rabbit was evaluated with this system after 5 days of intravenous AmB administration (1 mg/kg/day) and AmB concentrations measured by RRS were compared to those measured by high-performance liquid chromatography (HPLC). AmB exhibited a unique spectral peak at 1557 cm(-1). Integrated area of this peak linearly correlated with AmB concentration in our model AC. When integrated peak area from multiple in vivo measurements in one animal at steady-state was plotted on this correlation curve, we were able to predict AmB levels. These closely approximated those measured by HPLC. These measurements were not significantly affected by photobleaching or depth profile at acquisition. RRS at 406.7 nm is a method that may be useful for non-invasive monitoring of intraocular AmB levels. This instrument can help physicians decide when repeat, invasive delivery of this drug is warranted based on measurement of actual drug levels in the AH. Also, there is the potential to measure the ocular concentrations of other pharmaceutical agents with similar instruments.     

An interstitial deletion of 6p24-p25 proximal to the FKHL7 locus and including AP-2α that affects anterior eye chamber development.

The FKHL7 gene has been implicated in the pathogenesis of glaucoma/autosomal dominant iridogoniodysgenesis (IGDA) (IRID1). This has been supported by mutations in some glaucoma and IGDA patients and the development of anterior eye chamber anomalies in patients with 6p deletions affecting the 6p25 region. We report a case with anterior eye chamber anomalies and an interstitial deletion of 6p24-p25 that does not include the FKHL7 gene, suggesting the possible additional involvement of another locus, within 6p24-6p25, in anterior eye chamber development. A candidate gene is AP-2alpha, which is contained within the deleted segment and plays a role in anterior eye chamber development.     

Minimally invasive spectroscopic system for intraocular drug detection

A novel, minimally invasive measurement technique has been developed for the detection of drugs in the anterior chamber of the eye. Presently there is no satisfactory, real-time detection method available to the ophthalmic community. Accurate determination of drug concentrations in the eye would be of great value and assistance to researchers and manufacturers of ophthalmic drugs and ocular implants, to enable a better understanding of intraocular pharmacokinetics. At present researchers use techniques of direct sampling of the aqueous humor from laboratory animal eyes into which the drug has been introduced topically or systemically. Rabbit eyes are frequently used in this context. Sampling via paracentesis is invasive, and does not yield a continuous measurement. Our approach to addressing this measurement requirement is, in effect, to turn the eye into a cuvette and use optical absorbance spectroscopy measurements to detect drug concentrations. A novel contact lens has been designed using commercial, off-the-shelf, optical design software. The lenses have been optimized to direct light across the anterior chamber of a rabbit's eye. Practical demonstration and characterization of light propagation across the eye have been undertaken and are reported. Preliminary results of the identification of drug compounds introduced into model eyes are also reported.     

Identification of a fluorescein tracer model for determination of the flow rate of aqueous humor in the eye.

The continuous flow of the aqueous humor through the posterior and anterior chambers in the eye into Schlemm's canal is vital for the maintenance of a constant intraocular pressure. If the intraocular pressure rises above the normal range, several problems start appearing insidiously; for example, gradual visual field defects develop, leading ultimately to glaucoma. The determination of the flow rate of the aqueous humor is here performed by identifying a mathematical model after the free fluorescein concentration in the blood and in the anterior chamber of the eye has been measured. Experimental data obtained on rabbits are used in the analysis, and the flow rate of the aqueous humor in rabbit eyes is computed. This study demonstrates the feasibility of the approach in a clinical environment.     

The course of carrageenin-induced iridocyclitis in rabbits

On the basis of biochemical indices in the aqueous humor of the eye strictly related to intensity of inflammation, and morphologic observations with the slit-lamp microscope, dynamics of experimental carrageenin-induced inflammation of the anterior chamber of the eye was studied. Carrageenin-induced inflammation was characterized by intensity of changes in the aqueous humor within a few hours after infection of the inflammatory factor. Peak intensity of the disease process was observed six hours after administration of the inflammatory factor. Protein levels, seromucoid, sialic acid and proteolytic activity in the aqueous humor were correlated with intensity of clinical symptoms observed with the slit lamp. Carrageenin-induced inflammation of the anterior chamber of the eye is an entirely local reaction since the blood serum showed no significant abnormalities of the parameters that were studied. This model, based on biochemical and biomicroscopic studies, may prove useful in the studies of the dynamics of inflammation of the anterior chamber of the eye and for evaluation of anti-inflammatory drugs used in ophthalmology.     

Correlated or not: Glaucoma prevalence and modern industrialization

The higher prevalence of primary angle-closure glaucoma (PACG) among Eskimos, Chinese and Mongolians has long been acknowledged, while primary open-angle glaucoma (POAG) is common in blacks and Caucasians. However, in recent years, the incidence of Chinese POAG has increased to a level similar to that of Western countries, and the urban prevalence is higher than the rural one. Is this a coincidental result, or is it a consequence of modern industrialization? The etiology of glaucoma is believed to be due to both genetic and environmental factors. Genetics plays an important role in the growth of the eye, as demonstrated in ethnic variations in glaucoma prevalence and family studies. At the same time, changes in environmental factors have resulted in countries experiencing one of the most rapid epidemiological transitions in history. For the modern human eye to adapt to a more close-up working environment, and with more education requiring close reading, there have been some changes in the eye structure, including a deepening of the anterior chamber, an increase in myopia, a decrease of hyperopia, etc. The changes in these factors were closely associated with the pathogenesis of glaucoma. And of these factors, myopia may have been the most important contributor. Myopia, as an independent risk factor, may increase susceptibility to glaucomatous damage of the optic nerve in myopic eyes. Myopic eyes are more sensitive to intraocular pressure (IOP) (even normal IOP)-induced stress for the thinner lamina cribrosa and larger scleral canal than emmetropic eyes. Axial myopia has longer axial length of the eye and deeper anterior chamber than the normal eye, leading to a less chance to develop angle-closure glaucoma. Due to the increase in myopia among the younger generation in the process of industrialization and urbanization, we hypothesize that the prevalence of glaucoma is correlated with these changes, and that POAG could become more common in Eskimos, Chinese and other Asian descendants in the future.     

Intraocular Myeloma

Abstract

An eighty-seven year old female presented with complaints of pain in the left eye. She had a history of chronic open angle glaucoma that was under control with medication. She had lost all vision, and the eye had become very painful and inflamed. She was admitted with a diagnosis of endopthalmitis. Enucleation was performed and inspection of the specimen revealed a firm globe with a white mass extending over the iris and across the pupil in the anterior chamber. Microscopic evaluation with the hematoxylin and eosin stain revealed a plasma cell infiltrate involving the ciliary process, extending into the posterior chamber, occlusion of the retinal artery, and extensive loss of nerve fibers within the optic nerve. An accumulation of a pinkish and somewhat fibrillar material within the tumor and optic nerve was also observed. Stains for myelin and amyloid and a methyl green pyronine were performed, and immunoperoxidase for IgG, IgA, IgM, kappa and lambda.     

Intraocular Myeloma

Abstract

An eighty-seven year old female presented with complaints of pain in the left eye. She had a history of chronic open angle glaucoma that was under control with medication. She had lost all vision, and the eye had become very painful and inflamed. She was admitted with a diagnosis of endopthalmitis. Enucleation was performed and inspection of the specimen revealed a firm globe with a white mass extending over the iris and across the pupil in the anterior chamber. Microscopic evaluation with the hematoxylin and eosin stain revealed a plasma cell infiltrate involving the ciliary process, extending into the posterior chamber, occlusion of the retinal artery, and extensive loss of nerve fibers within the optic nerve. An accumulation of a pinkish and somewhat fibrillar material within the tumor and optic nerve was also observed. Stains for myelin and amyloid and a methyl green pyronine were performed, and immunoperoxidase for IgG, IgA, IgM, kappa and lambda.