The bioavailability and nonlinear pharmacokinetics of MK-679 in humans

MK-679 (R(?)-3-((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)(3-(dimethylamino)-3-oxopropyl)thio)methyl)thio(propanoic acid) is a potent and specific LTD₄-receptor antagonist. The disposition of MK-679 was investigated in a three-way crossover study in 12 healthy males receiving single intravenous doses of 75, 250, and 500 mg of MK-679. A greater than proportional increase in the area under the plasma concentration—time curve of MK-679 was observed with increase in dose. The plasma concentration data for each subject fitted well to the differential equations for a two-compartment model with linear tissue distribution and Michaelis-Menten elimination from the central compartment, indicating that the elimination of MK-679 in humans is saturable. In a previous study, the disposition of MK-679 in humans was also dose-dependent when given together with its S(+)-isomer, L-668,018. Thus, the disposition of MK-679 in humans is dose-dependent regardless of the presence of its stereoisomer. Also, the bioavailability of MK-679 was determined in six healthy males receiving simultaneously an oral dose of 250 mg of MK-679 and intravenous infusion of 1 mg ¹⁴C-MK-679. Results of this study indicate that the oral bioavailability of MK-679 is nearly quantitative.     

角膜地形图与角膜曲率计在白内障手术前后评价

本文应用计算机辅助的角膜地形图系统TMS-1和角膜曲率计TOPCONOM-4同时测定了200例(278眼)的角膜地形图和中央角膜屈光状态。比较了角膜地形图的模拟角膜曲率SIMK值和角膜曲率计的垂直和水平屈光度。结果显示,白内障术前组116例150眼的SIMK平均值分别为44.22D(垂直轴)和44.26D(水平轴),角膜曲率计的中央屈光度垂直轴平均为44.16D,水平轴为44.23D。统计学处理表明,2种组方法的结果之间差异无显著性(P>0.05),第2种术后组67例90眼的SIMK平均值分别为46.37D(垂直轴)和43.06D(水平轴),角膜曲率计的中央屈光度垂直轴平均为46.09D,水平轴平均为42.88D,统计学处理二种方法的结果之间差异无显著性(P>0.05)。研究提示,角膜地形图系统的模拟角膜曲率SIMK值和角膜曲率计的屈光度无论在白内障手术前还是在手术后其结果是一致的,临床应用具有同等的价值。但是,当角膜中央屈光度异常范围小于3毫米,角膜混浊,角膜严重不规则散光时,角膜曲率计不能满足临床需要。而计算机辅助的角膜地形图系统则具有极大的诊断及检测价值。眼科学报 1994;10:85—89。     

人工晶体植入术后继发青光眼的临床分析

报告14例后房型人工晶体植入术后继发青光眼患者，男性8例，女性6例。均为单眼发病，其中10例发生在术后1个月以内，另4例发生在1～3年以后。其中开角型8例，闭用型6例。7例经抗青光眼药物治疗可控制眼压，4例用激光治疗，另3例需行抗青光眼手术。治疗前矫正视力达0．5以上者为28％，治疗后矫止视力达0．5以上增加至50％。所有病例均眼压控制良好、视力不良原因为青光眼世视神经萎缩，提示早期发现的重要性。     

复治矽肺结核化疗效果观察

我们自１９８０～１９８８年对７９例复治矽肺结核进行化疗。其中绝大多数为慢性纤维化空洞性病例，均经细菌学证实，并由尘肺诊断组认定为矽肺合并结核。本组病例分别以ＫＭ、ＩＮＨ、ＲＦＰ、ＰＺＡ，或ＳＭ、ＩＮＨ、ＲＦＰ、ＥＢ联合，分两阶段治疗１８个月，获痰菌阴转７９．２％，其中ＫＨＲＺ与ＳＨＲＥ组分别为９３．９％与６８．２％（Ｐ＜０．０５）。自疗程结束追踪２～８年，其细菌复阳率分别为６．４５％和１０．０％（Ｐ＞０．１）。并对影响其过去治疗失败的原因及对策进行了讨论。     

Renal vascular resistance in normal children – a color Doppler study

To investigate the relationship between age and renal vascular resistance and to establish nomative data of the systolic/diastolic ratio (S/D ratio), pulsatility index (PI), and resistant index (RI) of the renal artery in the normal pediatric population, we studied 252 normal children aged newborn to 13 years (a total of 449 kidneys) with a color Doppler unit. After the normality of the kidney was established, color flow mapping was performed to localize the segmental portion of the renal artery. Flow velocity waveforms were then obtained by pulsed Doppler, and S/D ratio, PI, and RI were calculated. Multiple regression analysis confirmed the age dependence of the S/D ratio, PI, and RI of the renal artery in normal children. Renal vascular resistance continuously declines after birth and stabilizes at the age of 102 – 130 months. Normative data for S/D ratio, PI, and RI of the renal artery in normal children were established for each age group. Since renal vascular resistance decreases with age and stabilizes at 8 – 10 years, we suggest using different normal ranges for each age group when studying renal vascular resistance in pediatric patients. Received October 5, 1995; received in revised form and accepted April 24, 1996     

Rigid contact lens decentration: a risk factor for corneal warpage

Clinically significant contact lens induced corneal warpage is seen in a small proportion of soft and rigid contact lens wearers. Previous studies using the keratometer have found no correlation between the fit of the lens and the induced topographic changes. In this study, using computer-assisted topographic analysis, seven eyes (four patients) with rigid contact lens-induced corneal warpage were noted to have topographic abnormalities that correlated with the decentered resting position of the contact lens on the cornea. The warpage topography for each of these corneas was characterized by a relative flattening of the cornea underlying the resting position of the contact lens. Lenses that rode high, for example, produced flattening superiorly and resulted in a relatively steeper contour inferiorly that simulated the topography of early keratoconus patients who had not worn contact lenses. After discontinuing contact lenses the corneal topography returned to a normal pattern in five eyes. Two eyes retained asymmetry that is not characteristic of normal corneas. Up to 6 months was required for the corneas to return to a stable topography after contact lens wear was discontinued.     

日本血吸虫尾蚴至童虫期超微结构变化与生理适应的关系

本文应用透射电镜观察比较日本血吸虫尾蚴和皮肤型童虫的体壁、腺体和消化道的超微结构。结果表明,从尾蚴至皮肤型童虫转变过程,其体壁和钻腺的超微结构发生明显改变,但头腺及消化道则未见明显变化。这些变化与其相应的微环境密切相关。     

Increased expression of MHC class II antigens in rejecting canine lung allografts

Expression of major histocompatibility complex class II antigens was investigated in the normal lungs and in lung allografts of mongrel dogs after single-lung transplantation. Cryostat sections were stained with an indirect immunoperoxidase technique that used B1F6 and 7.5.10.1 as anti-MHC class II monoclonal antibodies. In the normal lungs and native lungs of the recipient dogs after single-lung transplantation, only some cells of lymphoid tissue and macrophages/dendritic cells were MHC class II-positive. During acute rejection, increased infiltration with MHC class II-positive cells in perivascular, peribronchial, and interstitial areas and intraalveolar spaces was found in lung allografts. In addition, expression of MHC class II antigens was induced on the bronchial epithelium and vascular endothelium. Induced expression of MHC class II antigens on the bronchial epithelium and vascular endothelium in rejecting lung allografts was found as early as two days after single-lung transplantation. The intensity of MHC class II antigen expression on bronchial epithelium and vascular endothelium in graft lungs increased with the progression of rejection response and directly correlated with the bronchoalveolar lavage fluid (BALF) levels of biochemical markers, as tumor necrosis factor alpha, gamma-interferon (IFN-gamma), interleukin 2 (IL-2) and soluble interleukin 2 receptor (SIL-2R). Abnormal expression of MHC class II antigens on bronchial epithelium and vascular endothelium and abnormal elevation of BALF levels of the cytokines in lung allografts could be prevented by cyclosporine (CsA) treatment. Our results suggested that MHC class II antigen expression could be induced on the bronchial epithelium and vascular endothelium of canine lung allografts during acute rejection. This abnormal expression of MHC class II antigens on bronchial epithelium and vascular endothelium of graft lungs may serve as a specific index for diagnosis of lung allograft rejection when infection as an inducing factor can be excluded. Furthermore, bronchial epithelium and vascular endothelium of lung allografts have become MHC class II-positive, and are likely to be the targets for low-grade rejection, resulting in the development of bronchiolitis obliterans and occlusive vascular disease in lung allografts.     

中国汉族群体D4S111位点的遗传多态性研究

目的：研究中国汉族群体中α艾杜糖苷酶基因Ｄ４Ｓ１１１位点的遗传多态性。方法：采用扩增片段长度多态性（ＡｍｐＦＬＰ）分析技术，检测了广州地区汉族无血缘关系健康个体９７名。结果：Ｄ４Ｓ１１１位点，在９７名无关个体中发现５个等位基因和９种基因型，等位基因片段长度为８３０～５１０ｂｐ，基因频率为０００５２～０３６０８，ＰＩＣ为０５９６６，杂合性为０７８。结论：中国汉族群体中Ｄ４Ｓ１１１位点具有高度多态性，并与其它种族间存在差异性。     

真皮下血管网岛状皮瓣抗菌力的实验研究

为研究真皮下血管网薄皮瓣用于感染创面的可行性，在家猪臀部两侧分别形成以旋髂深血管主干分支为蒂的传统岛状皮瓣和远侧５０％修薄的真皮下血管网岛状皮瓣。用细菌计数、吖啶橙荧光染色测定白细胞吞噬指数和白细胞内杀菌率，应用激光多普勒、墨汁灌注、透明标本等方法，对两种皮瓣的抗菌力作自身对照研究。结果表明，真皮下血管网岛状皮瓣的抗菌力明显降低，可能与皮瓣修薄后血供减少，白细胞功能相应降低有关。