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。     

An approach to haemorrhoids

OBJECTIVE: Many patients with haemorrhoids are investigated because of the fear of missing colorectal cancer (CRC). The aim of this study was to determine whether a primarily clinical approach regarding the need for investigation was safe and did not miss patients with CRC. PATIENTS AND METHODS: Data was collected prospectively on 589 consecutive patients with the principle diagnosis of haemorrhoids at first clinic visit. All had clinical assessment including rigid sigmoidoscopy and were treated by phenol injection or banding. They were categorized for (1) no review unless symptoms persisted -'One Stop SOS' (2) outpatient review or (3) investigation. To check for the development of CRC they were contacted by postal questionnaire or telephone interview with a minimum of one year from diagnosis and treatment. All 589 patients were cross-referenced with the Pathology database and the Hospital Information Services System. RESULTS: Four hundred and sixty-nine (80%) answered the questionnaire; 352 patients (60% of the total group) fell in the 'one stop SOS' outpatient category; 95 (16%) patients were followed up to review response to treatment for large haemorrhoids; 105 (18%) were investigated with barium enema (12%), flexible sigmoidoscopy (4%), colonoscopy (1%) and miscellaneous (1%); 37 (6%) patients were either given a haemorrhoidectomy date or referred on with a different diagnosis. No patients selected for 'one-stop' treatment developed CRC. Five (0.8%) patients were diagnosed with CRC after appropriate investigation was instituted for suspicious symptoms. One patient with distal transverse colon cancer had a delayed diagnosis as she was investigated initially by flexible sigmoidoscopy. CONCLUSION: Most patients with the primary diagnosis of symptomatic haemorrhoids do not need investigation.     

血瘀证的研究发展脉络与评述

主要从4个方面论述了血瘀证50年来研究进展．理论研究，着重从古今文献论述血瘀证定义和含义；客观研究，着重对生理、生化、血液流变学、免疫学、病理学和微循环等方面对血瘀证进行研究；血瘀证的动物模型研究，主要对血瘀证动物模型的建立与造模方法和途径进行研究；诊断标准研究，包括诊断标准、诊断指标的研究。并对上述内容进行了评述，并提出了展望。     

Health-related quality of life in Taiwanese patients with bronchial asthma.

BACKGROUND AND PURPOSE: Health-related quality of life (HRQOL) is primarily an assessment of how domains of life are affected by health. This study investigated the factors influencing HRQOL of Taiwanese patients with bronchial asthma. METHODS: A cross-sectional study was conducted to assess the factors influencing HRQOL. The sample consisted of 242 outpatients with bronchial asthma. The Chinese language version of the St. George's Respiratory Questionnaire was used to measure HRQOL. Data were analyzed using simple regression and multiple regression. RESULTS: Age, marital status, level of education, asthma severity, peak expiratory flow, and previous hospital admissions were found to be predictors of HRQOL. Gender, duration of disease, and history of emergency visits were not correlated with HRQOL. The variables entered in the HRQOL model accounted for 17.4% of the total variance (adjusted R(2)). The regression coefficients indicated that the mean scores increased 7.68 in patients with moderate to severe disease severity, and increased 7.34 in patients with a history of hospital admissions. The mean scores decreased 7.60 in married patients. CONCLUSION: This study found that marital status, asthma severity, and history of hospital admissions were major predictors of HRQOL in Taiwanese patients with bronchial asthma.     

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.