已治愈与未治愈屈光参差性弱视患者双眼间的波前像差特点

目的　探讨已治愈与未治愈屈光参差性弱视患者双眼间的波前像差特点。方法　收集在广西视光中心就诊并自愿参加本研究的屈光参差患者共91例，根据病史和矫正视力将所有患者分成两组:对照组（已治愈的屈光参差性弱视）31例、弱视组（未治愈的屈光参差性弱视）60例。对照组按照等效离焦度的高低，将每例患者双眼的数据分别归入原弱视眼组和原对侧眼组；弱视组按照矫正视力是否正常，将每例患者双眼的数据分别列入弱视眼组和对侧眼组。弱视组患者按年龄分为成年弱视22例、未成年弱视38例。所有患者均接受iDesign^?波前像差仪（美国AMO公司）检测，以均方根值（root mean square，RMS）形式表示总像差和各项高阶像差（RMS3~6）。配对t检验用于分析各组内双眼间的参数差异；独立样本t检验比较两组间的参数差异；Spearman相关分析和线性回归分析各亚组内变量间的相互关系。结果　对照组原弱视眼等效离焦度高于原对侧眼，差异有统计学意义（P<0.01）；弱视组弱视眼等效离焦度、总像差RMS均高于对侧眼，差异均有统计学意义（均为P<0.01）；其余参数如总高阶像差、三阶像差、四阶像差、五阶像差、六阶像差RMS，在两组内双眼间的差异均无统计学意义（均为P>0.05）。散瞳状态下成年弱视组、未成年弱视组双眼间等效离焦度、总像差RMS差异均有统计学意义（均为P<0.01），弱视眼均大于对侧眼。波前像差图像显示:对照组和弱视组双眼间总像差均呈非对称性、总高阶像差均呈相似性与对称性。将对照组、弱视组双眼间波前像差各参数差值进行组间比较，独立样本t检验结果提示:△等效离焦度以及△总像差RMS在两组之间的差异均有统计学意义（均为P<0.01），弱视组均大于对照组；其余参数在两组间的差异均无统计学意义（均为P>0.05）。对照组、弱视组内双眼的等效离焦度均与其自身总像差RMS呈正相关；等效离焦度与其他波前像差参数之间无相关性。线性回归分析结果显示:对照组内原弱视眼的等效离焦度与总像差RMS的回归方程为Y=0.16+0.798X(R²=0.633，F=50.031，P=0.000)，原对侧眼的等效离焦度与总像差RMS的回归方程为Y=1.278+0.611X(R²=0.522，F=31.613，P=0.000)；弱视组内弱视眼的等效离焦度与总像差RMS的回归方程为Y=-1.466+1.149X(R²=0.825，F=272.675，P=0.000)，对侧眼的等效离焦度与总像差RMS的回归方程为Y=1.101+0.832X(R²=0.632，F=99.561，P=0.000)。结论　散瞳状态下已治愈和未治愈的屈光参差性弱视患者等效离焦度和总像差形态在双眼间存在明显差异，但高阶像差在双眼间具有相似性和对称性。     

西安市城区重点中学2002～2004年度高中一年级学生动态眼屈光状况的横断面流行病学调查

目的 对在校中学生眼健康状况的基本情况进行调查,为青少年眼保健提供基础资料。方法 采用前瞻性调查设计,对高一学生眼眼压、动态眼屈光状态等指标进行采集,输入编辑的专项应用程序,用SPSS11．0软件行统计分析。结果 高一学生(平均年龄16岁)在正常动态情况下,近视眼的患病率93．8％,其中低度近视为46．4％,中度近视34％,高度近视13．4％,正视眼4．0％,远视眼2．1％。平均屈光度为(-3．29±2．49)D,其中低度近视平均(-1．79±0．75)屈光度(D),中度近视平均(-4．34±0．88)D,高度近视平均(-7．77±1．46)D。较初一年级相比,男女生屈光度数之间、左右眼远视组有显著性差异,左右眼之间已无显著性差异,各近视组度数明显增加。结论高中一年级学生这一人群的的屈光度状态较初一已发生了质的变化,与初三、高三的各项指标近似,提示初中三年级的屈光发育对以后的近视发展具有重要的意义;初三各项指标均高于高一这一结果提示,高中升学考试对学生的屈光状态有着一定的影响,也间接证明过度近距离用眼导致眼过度调节,形成调节性(假性)近视,这种近视可通过长时间的休息得到一定缓解和恢复原有屈光度。提示应针对高中一年级学生这一人群的用眼状态采取综合、简易的手段,对其近视度数进行医疗干预。     

高中各年级动态眼屈光状况的横断面流行病学调查

目的:对在校中学生眼健康状况中的动态屈光基本情况进行横断面调查,为青少年眼保健提供基础资料。方法:采用前瞻性调查设计,对西安市城区重点中学2002/2004年度高中学生1385人2770眼动态屈光状态等指标进行采集,输入编辑的专项应用程序,用SPSS11.0软件行统计分析。结果:高中学生(年龄16～18岁)在正常动态情况下,近视眼的发病率为94%,其中41.7%的低度近视,40.0%的中度近视,12.3%的高度近视;正视眼仅占3.8%,尚有2.2%为远视眼;3个年级组各屈光构成比相比,高度近视、远视组在3a间基本稳定,而高三年级在低度近视组、正视组明显下降的同时,中度近视组明显升高。高中平均屈光度(-3.39±2.34)D,其中低度近视平均(-1.83±0.75)D,中度近视平均(-4.38±0.85)D,高度近视平均(-7.49±1.28)D。3个年级平均屈光度为:高一(-3.29±2.49)D,高二(-3.09±2.31)D,高三(-3.57±2.25)D,组间和总体均有显著性差异(P<0.01)。女生组平均屈光度(-3.46±2.35)D,大于男生组(-3.31±2.32)D(P=0.093);其他屈光度组间在性别中无显著性差异。眼别中右眼平均屈光度(-3.51±2.25)D大于左眼(-3.27±2.42)D(P=0.008)。女生右眼平均屈光度大于左眼(P=0.030)。远视组右眼平均屈光度小于左眼(P=0.004)。结论:高中学生屈光状态趋于平稳的同时,近视眼的构成比中在高三年级继续有低度近视向中度近视发展变化,致使高中总体屈光状态呈平缓近视化趋势;女生在近视化进展期早于男生,女生右眼在高中屈光近视化进展期早于左眼,应针对高中年级学生这一人群的用眼状态采取综合、简易的手段,对其近视度数进行医疗干预。     

尼群地平缓释微球的制备及其体内外相关性的研究

目的制备具有固体分散体结构的尼群地平缓释微球 ,并筛选具有良好体内外相关性的释放介质。方法采用球晶造粒法制备尼群地平缓释微球 ,考察微球的粒径、载药量、包封率及释放行为 ,并根据 6只试验犬体内药物动力学试验结果 ,将不同时间的吸收分数与不同释放介质的相应时间点的体外累积释放百分数作线性回归 ,筛选具有良好体内外相关性的释放介质。结果制备的微球的粒径随搅拌速度的增加而减少 ,包封率均在 96 80 %以上 ,药物从微球中的释放速度随处方中固体分散体载体量的增加而增加 ,随阻滞剂量的增加而减小。以 1 7 4mmol L十二烷基硫酸钠为释放介质时 ,体外累积释放百分数与体内吸收分数相关系数较好 (r =0 985 1 ) ,方程为Fa =1 64 5 8ft-2 7 64 2。结论该方法较适用于难溶性药物制备缓释微球。以 1 7 4mmol L十二烷基硫酸钠水溶液为释放介质可作为控制微球内在质量的标准     

Practical approaches to dose selection for first-in-human clinical trials with novel biopharmaceuticals

Recent advances in our understanding of disease biology, biomarkers, new therapeutic targets, and innovative modalities have each fueled a dramatic expansion in the development of novel human therapeutics. Many are biotechnology-derived biologics possessing high selectivity and affinity for their intended target; as such they often pose challenges in the development path to approval. One challenge is the selection of the first-in-human (FIH) dose. This process has come under increased scrutiny as a result of a FIH trial with a super-agonist monoclonal antibody (TGN1412), which resulted in significant injury to healthy volunteers. Regulatory agencies have responded with supplemental guidance for the development of novel therapeutics. The intent of this paper is to provide experience-based insight, with relevant examples, for those planning the first administration of novel biopharmaceuticals in humans.     

An Australasian assessment of the basic treatment equivalent model derived from New South Wales data

The current method of assessment of radiation oncology linear accelerator throughput is either by patients per unit time or fields per unit time. This, however, does not take into consideration the complexity of different treatment techniques or of casemix. A model has been developed in an earlier study, called ‘basic treatment equivalent’ (BTE), to measure patient throughput of a linear accelerator, which includes consideration of the complexity of treatment techniques. The present study compared the BTE model with the current best measure of patient throughput of fields per hour. All 37 departments in Australia and New Zealand were invited to participate in testing the model, and 36 agreed to participate. The study period for each department was a consecutive 4 weeks between August and December, 1996. The prospective data collected were the total BTE units treated per linear accelerator per day, the total number of patients and fields treated per linear accelerator per day, and the total linear accelerator hours of operation per day excluding calibration time and significant breaks of linear accelerator time such as planned meal breaks. The treatment breaks between consecutive treatment fractions were not excluded from the linear accelerator treatment time. The throughput data for 36 departments (92 linear accelerators) were collected over the 4-week study period. The average throughput for the departments was 10.8 fields per hour and 4.2 patients per hour. The average BTE per department was 5.7 BTE per hour. The average BTE per episode per department was 1.38. The BTE model was found to be a more sensitive measure of productivity compared with fields per hour (P < 0.001). Some treatment techniques were thought to be not well represented by the BTE formula, particularly those techniques where junctions were present. The BTE model is a more sensitive measure than fields per hour and better reflects the variations in complexity in techniques. Despite this result there is further refinement to be performed to make the model even more sensitive.     

Refinement of the basic treatment equivalent model to reflect radiotherapy treatment throughput using Australasian data

A model of radiotherapy linear accelerator throughput has been developed and shown to be a more sensitive measure of throughput than current measures of throughput. The present study aims to develop a more sensitive basic treatment equivalent (BTE) model that still measures linear accelerator throughput and considers some of the shortcomings of the previous model. All radiation oncology departments in Australia and New Zealand were invited to participate. Departments were asked to time with a stopwatch all episodes of radiotherapy treatment over a 4-week period. Data collected for each treatment fraction included treatment intent, tumour site, patient age, Eastern Cooperative Oncology Group (ECOG) performance status, number of fields used, number of wedges used, number of junctions, number of shielding blocks used, whether the treatment was the first fraction, the use of general anaesthesia and whether port films or electronic portal imaging was used. Twenty-six departments of radiation oncology (70%) participated in this trial. A total of 7929 fractions of treatment, administered to 2424 patients, were timed. The factors found to most significantly impact on treatment duration on multivariate analysis were the type of fraction (first fraction was longer than subsequent fractions), type of beam (electrons were quicker than photons, which were quicker than mixed), number of fields, number of shields, number of junctions, number of port films and performance status (ECOG < 2 vs > 2). The age of the patient, number of compensators and the sex of the patient were not significant. The relationships between factors were assessed, and models of measuring linear accelerator throughput which consider complexity corrections were derived. It is possible to show that linear accelerator throughput is poorly measured by just considering numbers of patients or fields treated per unit time; and that other factors that impact on treatment duration must be considered. A more sensitive model of patient throughput is suggested; but even when a large number of factors are considered, some insensitivity still remains in the model.     

Ether oxygenate additives in gasoline reduce toxicity of exhausts

Fuel additives can improve combustion and knock resistance of gasoline engines. Common additives in commercial fuels are “short-chain, oxygen containing hydrocarbons” such as methyl tert-butyl ether (MTBE) and ethyl tert-butyl ether (ETBE). Since these additives change the combustion characteristics, this may as well influence toxic effects of the resulting emissions. Therefore we compared toxicity and BTEX emissions of gasoline engine exhaust regarding addition of MTBE or ETBE.     

Potential of long-term dietary administration of rosemary in improving the antioxidant status of rat tissues following carbon tetrachloride intoxication

In this study, 24 Wistar rats were allocated to 4 groups of 6 animals each. Groups 1 and 2 were fed a basal diet, while groups 3 and 4 were fed the basal diet supplemented further with ground rosemary at 1% level. Following 6-weeks feeding, groups 2 and 4 were injected 1 ml CCl₄/kg bw and after six hours all animals were sacrificed. Results showed that feeding rosemary before CCl₄ treatment resulted in decline (P < 0.05) of the increased aspartate transaminase, alanine transaminase and alkaline phosphatase activities and increase (P < 0.05) of the reduced cholesterol and triacylglycerols in serum. It also decreased (P < 0.05) lipid peroxidation and increased (P < 0.05) the reduced hydroxyl anion radical and hydrogen peroxide scavenging activities in serum, liver, kidney and heart tissues. In addition, it increased (P < 0.05) the reduced ABTS radical cation and the superoxide anion scavenging activities in all tissues except in heart and in kidney and heart tissues, respectively. These results suggest that dietary rosemary has the potential to become a promising functional food component.     

Derivation of a reference dose and drinking water equivalent level for 1,2,3-trichloropropane

In some US potable water supplies, 1,2,3-trichloropropane (TCP) has been present at ranges of non-detect to less than 100 ppb, resulting from past uses. In subchronic oral studies, TCP produced toxicity in kidneys, liver, and other tissues. TCP administered by corn oil gavage in chronic studies produced tumors at multiple sites in rats and mice; however, interpretation of these studies was impeded by substantial premature mortality. Drinking water equivalent levels (DWELs) were estimated for a lifetime of consumption by applying biologically-based safety/risk assessment approaches, including Monte Carlo techniques, and with consideration of kinetics and modes of action, to possibly replace default assumptions. Internationally recognized Frameworks for human relevance of animal data were employed to interpret the findings. Calculated were a reference dose (=39 μg/kg d) for non-cancer and Cancer Values (CV) (=10–14 μg/kg d) based on non-linear dose–response relationships for mutagenicity as a precursor of cancer. Lifetime Average Daily Intakes (LADI) are 3130 and 790–1120 μg/person-d for non-cancer and cancer, respectively. DWELs, estimated by applying a relative source contribution (RSC) of 50% to the LADIs, are 780 and 200–280 μg/L for non-cancer and cancer, respectively. These DWELs may inform establishment of formal/informal guidelines and standards to protect public health.