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71.
JB Thomas MJ Fall JB Cooper RB Rothman SW Mascarella H Xu JS Partilla CM Dersch KB McCullough BE Cantrell DM Zimmerman FI Carroll 《Canadian Metallurgical Quarterly》1998,41(26):5188-5197
A three-component library of compounds was prepared in parallel using multiple simultaneous solution-phase synthetic methodology. The compounds were biased toward opioid receptor antagonist activity by incorporating (+)-(3R,4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (a potent, nonselective opioid pure antagonist) as one of the monomers. The other two monomers, which included N-substituted or unsubstituted Boc-protected amino acids and a range of substituted aryl carboxylic acids, were selected to add chemical diversity. Screening of these compounds in competitive binding experiments with the kappa opioid receptor selective ligand [3H]U69,593 led to the discovery of a novel kappa opioid receptor selective ligand, N-?(2'S)-[3-(4-hydroxyphenyl)propanamido]-3'-methylbutyl?-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (8, RTI-5989-29). Additional structure-activity relationship studies suggested that 8 possesses lipophilic and hydrogen-bonding sites that are important to its opioid receptor potency and selectivity. These sites appear to exist predominantly within the kappa receptor since the selectivity arises from a 530-fold loss of affinity of 8 for the mu receptor and an 18-fold increase in affinity for the kappa receptor relative to the mu-selective ligand, (+)-N-[trans-4-phenyl-2-butenyl]-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (5a). The degree of selectivity observed in the radioligand binding experiments was not observed in the functional assay. According to its ability to inhibit agonist stimulated binding of [35S]GTPgammaS at all three opioid receptors, compound 8 behaves as a mu/kappa opioid receptor pure antagonist with negligible affinity for the delta receptor. 相似文献
72.
CM McDonald 《Canadian Metallurgical Quarterly》1998,9(1):9-48
This article has reviewed the clinical approach to the diagnostic evaluation of progressive neuromuscular diseases with an emphasis on relevant neuromuscular history, family history, clinical examination findings, laboratory studies, and a brief discussion of the role of muscle biopsy. Molecular genetic and immunocytochemistry studies of muscle have been major advances in the diagnostic evaluation of the neuromuscular disease patient; however, all diagnostic information must be interpreted within the context of relevant clinical information. In some instances, a precise diagnosis is not medically possible; however, the accurate characterization of an individual patient within the most appropriate NMD clinical syndrome often allows the clinician to provide the patient and family with accurate prognostic information and anticipatory guidance for the future. After synthesizing all available clinical and diagnostic information, the physiatrist or neurologist may at times determine that an NMD patient has an inappropriate diagnosis warranting further diagnostic evaluation. This issue focuses on the rehabilitation of progressive neuromuscular diseases with an emphasis on optimization of health, prevention or minimization of complications, and enhancement of quality of life. Appropriate rehabilitation approaches require an accurate diagnosis. In addition, patient quality of life in NMD depends on access to current and accurate information. The first step in providing accurate information and appropriate treatment is constantly ensuring that NMD patients have appropriate diagnoses based on a through evaluation of clinical information and appropriate application of current medical science and available diagnostic technology. 相似文献
73.
In this paper we present the dosimetric data of a Therapax DTX300 kilovoltage x-ray unit for endocavitary rectal irradiation. The unit if operated at tube voltage of 40-60 kVp (30 mA) with an added filtration of 0.2-0.4 mm Al generates acceptable beam qualities comparable to those of the original Papillon technique. Relative dosimetric measurements were performed at the cone end (37.2 cm SSD) of a 3 cm diameter rectal cone using various detectors to ensure the accuracy. A Monte Carlo method was used to calculate correction factors for the diode used in the percentage depth-dose (PDD) measurement, and to study the effect of the detector size on the beam profile. The PDD data were determined using the diode measurement corrected for its energy and angular response. It was found that the PTW N23342 and Markus parallel-plate chamber can be used directly to measure the PDD for this beam quality with 2% uncertainty. Measurement and Monte Carlo results have shown that the detector size has a significant effect on the penumbral profile. Film and diode detectors have a better spatial resolution compared to ionization chambers, but they may give an incorrect profile tail due to either nonlinear response at low energy or angular dependence. This can be corrected using the ionization-chamber measurement, based on the Monte Carlo analysis. The isodose distributions for this x-ray unit are presented. 相似文献
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77.
R Kneen NG Pham T Solomon TM Tran TT Nguyen BL Tran J Wain NP Day TH Tran CM Parry NJ White 《Canadian Metallurgical Quarterly》1998,27(4):845-850
PURPOSE: To review the University of Florida experience in treating ependymomas, analyze prognostic factors, and provide treatment recommendations. METHODS AND MATERIALS: Forty-one patients with ependymoma and no metastases outside the central nervous system received postoperative radiotherapy with curative intent between 1966 and 1989. Ten patients had supratentorial lesions, 22 had infratentorial lesions, and 9 had spinal cord lesions. All patients had surgery (stereotactic biopsy, subtotal resection, or gross total resection). Most patients with high-grade lesions received radiotherapy to the craniospinal axis. Low-grade intracranial lesions received more limited treatment. Spinal cord lesions were treated using either partial spine or whole spine fields. RESULTS: Of 32 intracranial tumors, 21 recurred, all at the primary site; no spinal cord tumors recurred. Overall 10-year survival rates were 51% (absolute) and 46% (relapse-free); by tumor site: spinal cord, 100%; infratentorial, 45%; supratentorial, 20% (p = 0.002). On multivariate analysis, tumor site was the only factor that influenced absolute survival (p = 0.0004); other factors evaluated included grade, gender, age, duration of symptoms, resection extent, primary tumor dose, treatment field extent, surgery-to-radiotherapy interval, and days under radiotherapy treatment. CONCLUSIONS: Patients with supratentorial or infratentorial tumors receive irradiation, regardless of grade. Craniospinal-axis fields are used when spinal seeding is radiographically or pathologically evident. Spinal cord tumors are treated using localized fields to the primary site if not completely resected. Failure to control disease at the primary site remains the main impediment to cure. 相似文献
78.
S Bergamaschi F Battaini M Trabucchi M Parenti CM Lopez S Govoni 《Canadian Metallurgical Quarterly》1995,12(6):497-503
The effect of prolonged (72 h) ethanol (200 mM) exposure on the labeling of L-type (using tritiated PN 200-110) and N-type (using iodinated omega-conotoxin) voltage-dependent calcium channels was investigated in cultured NG 108-15 cells. In undifferentiated cells ethanol produced an 80% increase in PN 200-110 Bmax and no changes in omega-conotoxin binding. Differentiation had a profound effect on the response of cells to ethanol, which in differentiated neuron-like cells decreased omega-conotoxin binding (-53.5%) leaving PN 200-110 labeling of L-type channels unaffected. The effect was time dependent and reversible upon ethanol withdrawal. The decreased omega-conotoxin binding was accompanied by a reduced ability of omega-conotoxin to inhibit K+ -stimulated calcium uptake. The results demonstrate that in cultured NG 108-15 cells ethanol differentially affects DHP and omega-conotoxin-sensitive, voltage-dependent calcium channels and that the effect is also modulated by differentiation of the cell to a neuronal phenotype. 相似文献
79.
80.
N Reinisch S Kiechl C Mayr P Schratzberger S Dunzendorfer CM K?hler T Buratti J Willeit CJ Wiedermann 《Canadian Metallurgical Quarterly》1998,28(10):787-792
BACKGROUND: In atherosclerosis, both reductions and elevations in plasma levels of antioxidants have been reported. This study investigated total antioxidant capacity of plasma from subjects with atherosclerotic disease. MATERIALS AND METHODS: The study population consisted of 48 men with or without carotid atherosclerosis. At baseline (1990) carotid arteries were evaluated by duplex sonography and plasma samples were obtained for testing antioxidant capacity by two different test systems. One assay system used neutrophils from healthy volunteers as a source of oxygen free radicals activating the non-fluorescent dichlorofluorescin diacetate in the presence of antioxidant containing plasma from study subjects. In the other test system, total plasma antioxidants were detected colorimetrically by using 2,2'-azino-di-(3-ethylbenzthiazoline sulphonate), metmyoglobin and superoxide in the presence of plasma. Carotid arteries were re-evaluated for the development of new plaques 5 years later (1995). RESULTS: Increased baseline total antioxidant capacity of plasma was significantly associated with the development of new atherosclerotic lesions during a period of 5 years. CONCLUSIONS: Endogenous antioxidant capacity of plasma is increased in patients with active atherosclerotic disease. As scavenging of oxygen free radicals is thought to protect from atherogenesis, elevated antioxidative capacity may represent an adaptive mechanism. 相似文献