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.     

Carotid-cavernous sinus fistula associated with a primitive trigeminal artery

Carotid-cavernous sinus fistulas are not rare, but they have never been reported in association with persistent primitive trigeminal artery. We recently encountered such a case. The Jaeger-Hamby procedure was employed, with mandatory occlusion of the primitive trigeminal artery.     

脊髓手术中体感诱发电位监测的临床研究

报告３０例脊髓手术中体感诱发电位（ＳＥＰ）连续监测的临床研究结果。ＳＥＰ记录包括脊髓ＳＥＰ（ＳＳＥＰ）和皮层ＳＥＰ（ＳＣＥＰ）。麻醉药物对ＳＥＰ有一定程度影响，ＳＣＥＰ相对较大。认为，至少术中ＳＥＰ潜伏期延长不超过８％和波幅降低不超过５０％，不会引起术后并发症，超过该范围由于病例较少，尚不能肯定与预后的关系，需进一步探讨。     

Monokines produced by macrophages stimulate the growth of osteoblasts

We have previously reported that the J774A.1 macrophage-like tumor cell line produces two potent monokines which stimulate the growth of osteoblasts and chondrocytes. These growth factors, which have an affinity for heparin-agarose, have been termed HEP I (a 30 Kd PDGF-like molecule) and HEP II (an approximately 20 Kd molecule), respectively, based on their elution profile. Unlike HEP I, HEP II does not stimulate the growth of fibroblasts. Extensive biological and chromatographic studies disclosed that HEP II appears to be a unique bone cell mitogen unlike any known growth factor, including the FGFs, IL-1s, and TNFs, EGF, IGF-I and -II, TGF-beta, beta 2 microglobulin, G-CSF, CSF-1 and GM-CSF. To characterize more fully the effects of the macrophage-derived monokines on osteoblast growth and function, clones were derived from calvaria explant cultures. Two clones, SDFRC-2.05 and SDFRC-3, were developed and found to exhibit osteoblastic characteristics, including high levels of alkaline phosphatase, synthesis of type I but not type III collagen, and an increased intracellular cAMP production in response to PTH. The SDFRC-3 cells exhibited a polygonal morphology like that of the explant-derived cells while SDFRC-2.05 cells exhibited a more fibroblastic morphology. When tested on the explant cultures and clones, HEP I and HEP II were found to stimulate DNA synthesis and increase protein per culture, but decreased alkaline phosphatase activity. Clone SDFRC-3 was found to be more responsive to HEP II than clone SDFRC-2.05. Both monokines were found to be more potent mitogens for bone cells than TGF-beta. HEP II, but not HEP I or TGF-beta, induced a transformation of bone cells from a polygonal to a fibroblastic morphology, suggesting the induction of migration prior to proliferation. Thus, macrophages may be responsible not only for bone repair but also for ensuring the linkage of bone formation to resorption during physiological remodeling.     

Image features of two rare mediastinal tumors: schwannoma of intrathoracic phrenic nerve and clear cell chondrosarcoma of the rib

The current report focuses on two patients of the same age who presented similar appearances on initial anteroposterior chest images. Follow-up images showed superoanterior and superoposterior mediastinal lesions. The first patient with noninvasive cystic thymoma was suspected before surgery, while the pathologic diagnosis was intrathoracic phrenic nerve schwannoma. The second patient was with an asymmetric, dumbbell-shaped paravertebral tumor over T3 and T4 on the left side. The preoperative…     

Serial CT findings of Paragonimus infested dogs and the Micro-CT findings of the worm cysts.

OBJECTIVE: To investigate the serial CT findings of Paragonimus westermani infected dogs and the microscopic structures of the worm cysts using Micro-CT. MATERIALS AND METHODS: This study was approved by the committee on animal research at our institution. Fifteen dogs infected with P. westermani underwent serial contrast-enhanced CT scans at pre-infection, after 10 days of infection, and monthly thereafter until six months for determining the radiologic-pathologic correlation. Three dogs (one dog each time) were sacrificed at 1, 3 and 6 months, respectively. After fixation of the lungs, both multi-detector CT and Micro-CT were performed for examining the worm cysts. RESULTS: The initial findings were pleural effusion and/or subpleural ground-glass opacities or linear opacities at day 10. At day 30, subpleural and peribronchial nodules appeared with hydropneumothorax and abdominal or chest wall air bubbles. Cavitary change and bronchial dilatation began to be seen on CT scan at day 30 and this was mostly seen together with mediastinal lymphadenopathy at day 60. Thereafter, subpleural ground-glass opacities and nodules with or without cavitary changes were persistently observed until day 180. After cavitary change of the nodules, the migratory features of the subpleural or peribronchial nodules were seen on all the serial CT scans. Micro-CT showed that the cyst wall contained dilated interconnected tubular structures, which had communications with the cavity and the adjacent distal bronchus. CONCLUSION: The CT findings of paragonimiasis depend on the migratory stage of the worms. The worm cyst can have numerous interconnected tubular channels within its own wall and these channels have connections with the cavity and the adjacent distal bronchus.     

TUVP手术时间对血红蛋白及电解质的影响

目的 了解经尿道前列腺汽化电切手术时间对血红蛋白及血清电解质的影响。方法 对64例经尿道前列腺汽化电切术患按手术时间分组，观察手术前后血红蛋白及血清电解质的变化。结果 手术时间对血清电解质的降低有的影响，对血红蛋白降低的影响不显。结论 减少TUR综合征的关键是要操作熟练，缩短手术时间及手术中注意止血。     

Neural network based tracking control of a flexible macro-micro manipulator system.

In this paper, we address the problem of stable tracking control of a flexible macro-micro manipulator (M(3)) system. A two-layer neural network is utilized to approximate the nonlinear robot dynamic behavior of the M(3) system, and the controllers for the macro and micro arms are developed without any need for prior knowledge of the dynamic model of the controlled M(3) system. A learning algorithm for the neural network using Lyapunov stability theory is derived. It is shown that both the tracking error and the weight-tuning error are uniformly ultimately bounded under this new control scheme. Simulation results are presented and compared to those obtained using a PD controller.