Effectiveness,nephrotoxicity, and therapeutic drug monitoring of polymyxin B in nosocomial pneumonia among critically ill patients

ObjectivesWe aimed to assess the effectiveness and nephrotoxicity of polymyxin B in critically ill patients with nosocomial pneumonia and to evaluate the utility of its therapeutic drug monitoring (TDM).MethodsWe retrospectively analyzed patients who received polymyxin B treatment for ≥48 h since the establishment of polymyxin B TDM in a 26‐bed tertiary referral intensive care unit. Univariate and multivariate analyses were conducted to assess the variables associated with polymyxin B effectiveness and nephrotoxicity.ResultsA total of 62 patients were enrolled. Most (56.5%) of the patients performed TDM, 54.3% of them reached the therapeutic target of area under curve across 24 h at steady state (AUC_ss,24h) of 50–100 mg h L⁻¹, and 10 patients had an AUC_ss,24h value of <50 mg h L⁻¹. Thirty‐six (58.1) and 31 (50.0%) patients had favorable clinical and microbiological responses, respectively. Reaching the therapeutic target of AUC_ss,24h (odds ratio [OR] = 13.15, p = 0.015), a favorable microbiological response (OR = 40.80, p = 0.00), and complicated with septic shock (OR = 0.12, p = 0.021) were independently associated with favorable clinical outcomes of polymyxin B treatment. The incidence of acute kidney injury (AKI) was 45.2%. A lower creatinine clearance (OR = 0.96, p = 0.008) and concomitant treatment with loop diuretics (OR = 5.93, p = 0.046) were predictive of nephrotoxicity.ConclusionOur findings show that TDM of polymyxin B is a valuable intervention, and the achievement of its optimal pharmacodynamic target can improve treatment outcome. Renal insufficiency and concomitant treatment with loop diuretics were found to be associated with the risk of nephrotoxicity.     

男男性行为者艾滋病暴露前预防用药性行为去抑制化情况

目的：了解男男性行为者（men who have sex with men,MSM）在参加暴露前预防用药（pre-exposure prophylaxis,PrEP）临床试验中是否存在性行为去抑制化现象及其影响因素。方法：采用非概率抽样法招募并筛选出108名MSM,随机分为77名服用药物组和31名空白对照组,第12、24、36、48周进行临床随访和问卷调查,问卷调查主要包括社会人口学特征,艾滋病相关知识、态度和行为等相关情况。采用单因素和多因素的广义估计方程分析MSM在参与PrEP中是否存在性行为去抑制化现象及其影响因素。结果：药物服用组MSM在参与PrEP的第12、24、36、48周的性伴个数中位数分别为1（0,6）、1（0,6）、1（0,10）、1（0,3）、1（0,3）,高危性行为次数中位数分别为1（0,26）、1.5（0,8）、1（0,12）、1（0,9）、2（0,30）;空白对照组性伴个数中位数分别为1（0,21）、1（0,2）、1（0,3）、1（0,3）、1（0,3）,高危性行为次数中位数分别为1（0,9）、1（0,6）、0.5（0,15）、0（0,10）、1（0,10）;多因素广义估计方程分析发现MSM在参与PrEP过程中性伴个数及高危性行为次数均没有发生改变（Z=-0.24,P=0.811;Z=0.93,P=0.355）,性行为方式为“1”和“0.5”的较性行为方式为“0”的拥有更多的性伴（Z=2.47,P=0.014;Z=2.24,P=0.025）;发生过商业性行为的MSM较没有发生过的拥有较少的性伴和高危性行为（Z=-2.82,P=0.005;Z=-2.28,P=0.023）;已婚较离异MSM发生较少的高危性行为次数（Z=-2.34,P=0.019）。结论：本研究中暂未发现PrEP中存在性行为去抑制化现象,性行为方式为“1”和“0.5”的MSM拥有较多性伴,是后期随访中的重点管理人群。还需进一步加强对艾滋病相关知识的科普。     

青少年颈椎病的病因病机及预防

青少年颈椎病很少有人研究，笔者在临床中发现高中学生中时有颈椎病发生，比例约占学生总数１５．７９％，年龄均在１５—１９岁间。通过对５００余名高中、小学生的坐姿、睡姿调查发现：学生从小学一年级就开始的铅笔习字和枕高不合标准—使坐姿、睡姿改变—迫使颈椎生理弧度改变—颈部生物力学早期综合性失衡—颈部解剖学、组织学改变—最终出现病理学改变—颈椎病发生。Ｘ线平片证实：学生颈椎病主要是颈椎曲度值改变，与增生关系不大。并针对青少年颈椎病出现的病因病机，提出了一套保健措施，自编《青少年颈部保健操》。希望引起学校、家长、教育、卫生等对青少年颈椎病预防的重视     

非穿透性小梁手术超声生物显微镜检查

目的：应用超声生物显微镜（ＵＢＭ）检查技术,探讨非穿透性小梁手术联合透明质酸钠生物胶植入手术区域解剖特点和房水引汉机制。方法：对１４例１６只眼行非穿透性小梁手术联合透明质酸钠生物胶植入的患者,在术后１～３个月内进行手术区域ＵＢＭ检查。检查的指标（项目）包括：巩膜瓣下形成液间腔的大小（宽和高）、透明质酸钠生物胶吸收的情况、剩余角膜小梁膜的厚度以及滤过泡的形态,并对结果进行分析。结果：１６只眼术前平均     

Detection of abnormal visual cortex in children with amblyopia by voxel-based morphometry

PURPOSE: To detect the abnormalities of gray matter in children with amblyopia by voxel-based morphometry (VBM). DESIGN: Prospective, nonrandomized clinical trial. METHODS: Thirteen children with amblyopia and 14 normally sighted children underwent magnetic resonance (MR) examination. The two groups were age-matched with a mean age of 5.8 years. In the amblyopia group, five children had strabismus amblyopia, and eight had anisometropic amblyopia. We analyzed the original 3-dimensional T1 brain images using the VBM module within the widely used analysis software package SPM2 (Welcome Department of Cognitive Neurology, London, United Kingdom). After normalization, segmentation, and smoothing of the images, comparison between amblyopic and control groups was derived for the gray matter of the entire brain using parametric statistics. RESULTS: The results of VBM analysis indicated that the amblyopic group had decreased gray matter density in the middle frontal gyrus, parahippocampal gyrus, fusiform gyrus, inferior temporal gyrus of the left hemisphere, and the bilateral calcarine cortices. The radii of these regions ranged from 12 to 36 voxels. These abnormalities were consistent with morphologic changes in brain regions related to visual function. CONCLUSIONS: Using MR and VBM analysis, we detected morphologic changes in the visual cortex of children with amblyopia, which may indicate developmental abnormalities of visual cortex during the critical growth period.     

CYP1A1 and CYP1B1 genetic polymorphisms and uterine leiomyoma risk in Chinese women

Purpose  The aim of the study was to evaluate the association of CYP1A1 and CYP1B1 polymorphisms with uterine leiomyoma in Chinese women. Methods  We investigated 100 women with clinically diagnosed uterine leiomyoma and 110 healthy normal subjects from Chinese women. The genetic distribution of two CYP1A1 polymorphisms at MspI, Ile462Val and four CYP1B1 polymorphisms at Arg48Gly, Ala119Ser, Leu432Val, Asp449Asp were analyzed by polymerase chain reaction–restriction fragment length polymorphism and DNA sequencing method. Results  All the SNPs showed polymorphisms in Chinese women. The genotype A/G and the allele G on Ile462Val was significantly different between uterine leiomyoma patients and controls (P < 0.05). Conclusion  These results suggest that the genotype of CYP1A1 Ile462Val was associated with the increased risk of uterine leiomyomas in Chinese women. Capsule This is the first report that demonstrates the polymorphism at Ile462Val of CYP1A1 to be associated with uterine leiomyoma in Chinese women.     

尿钙及尿微量白蛋白检测在妊高征早期诊断中的临床意义

目的　评价尿钙及尿微量白蛋白检测在妊高征早期诊断中的临床意义。方法　收集９８ 例孕２４～３２ 周健康孕妇的２４ 小时尿样,采用自动生化仪测定尿钙排泄量,放射免疫法测定尿微量白蛋白的排泄量,按最终是否发生妊高征分成妊高征组（１４ 例） 和正常妊娠组（８４ 例） 。结果　妊高征组尿钙排泄量为（１－４３±０－３７） ｍｍｏｌ／２４ｈ ,正常妊娠组为（３－２６±０－７５） ｍｍｏｌ／２４ｈ,妊高征组尿钙排泄量显著低于正常妊娠组（ Ｐ＜ ０－００５） 。妊高征组尿微量白蛋白排泄量为（１２－６８ ±６－８１） μｇ／２４ｈ ,正常妊娠组为（６－０８±３－４８） μｇ／２４ｈ,妊高征组尿微量白蛋白排泄量显著高于正常妊娠组（ Ｐ＜ ０－０５）。结论　在妊高征临床症状出现４～８ 周之前,即出现尿钙排泄量减少及尿微量白蛋白排泄量增多。这一特征可作为妊高征早期诊断的指标。     

杀虫畏对雄性大鼠肝微粒体酶的诱导及动力学性质的研究

杀虫畏对肝微粒体酶呈现明显诱导作用。对诱导生成的酶的动力学性质进行研究证明,诱导生成组和对照组的苯胺羟化酶,其米氏常数(km)和抑制常数(ki)极相近似;微粒体酶抑制剂SKF525-A对两组酶均呈现非竞争性抑制作用。因此,可以认为两组酶具有相同的动力学性质。     

蒽酮-硫酸法测定灵芝破壁孢子粉中多糖含量的研究

目的 建立灵芝破壁抱子粉中多糖含量的测定方法。方法 采用紫外分光光度法,检测波长为625nm,用葡萄糖为对照品,测定灵芝破壁抱子粉中多糖含量。结果 不同的提取方法对于多糖的提取率不同。最佳提取方法为沸水浴提取8h。结论 本法稳定可靠,简便快捷,适用于灵芝破壁抱子粉多糖含量测定。     

透皮淋巴靶向长春新碱传递体

长春新碱(vincristine,VCR)临床主要用于治疗急性淋巴细胞白血病、何杰金及非何杰金淋巴瘤，疗效确切，但由于具有较大的神经系统毒性和局部刺激性，限制了其在临床上的应用。为增加VCR的淋巴靶向性，以增强疗效，降低其毒副作用，采用薄膜-超声分散法制备长春新碱传递体(VCR-T)，并考察其制剂学性质、药代动力学特征及靶向性。所制备的VCR-T平均粒径为63 nm，包封率为59%；改良Franz扩散池研究发现其体外透皮过程符合多项式方程，12 h累积透皮百分率为67.4%；HPLC法测定VCR在大鼠体内的药代动力学及组织分布，以VCR注射液为对照，VCR-T使VCR在血液中滞留时间延长了12倍，大鼠淋巴中靶向指数增加了2.75倍。传递体可良好地载带VCR透过皮肤进入体循环，具有较好的淋巴靶向性，可作为新型的淋巴靶向给药系统。