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491.
LG Hamann RI Higuchi L Zhi JP Edwards XN Wang KB Marschke JW Kong LJ Farmer TK Jones 《Canadian Metallurgical Quarterly》1998,41(4):623-639
A new nonsteroidal antiandrogenic pharmacophore has been discovered using cell-based cotransfection assays with human androgen receptor (hAR). This series of AR antagonists is structurally characterized by a linear tricyclic 1,2-dihydropyridono[5,6-g]quinoline core. Analogues inhibit AR-mediated reporter gene expression and bind to AR as potently as or better than any known AR antagonists. Several analogues also showed excellent in vivo activity in classic rodent models of AR antagonism, inhibiting growth of rat ventral prostate and seminal vesicles, without accompanying increases in serum gonadotropin and testosterone levels, as is seen with other AR antagonists. Investigations of structure-activity relationships surrounding this pharmacophore resulted in molecules with complete specificity for AR, antagonist activity on an AR mutant commonly observed in prostate cancer patients, and improved in vivo efficacy. Molecules based on this series of compounds have the potential to provide unique and effective clinical opportunities for treatment of prostate cancer and other androgen-dependent diseases. 相似文献
492.
RI Hector 《Canadian Metallurgical Quarterly》1998,43(5):466-472
The effect of coadministration of ritonavir and didanosine (ddI) on the pharmacokinetics of these drugs was investigated in a single-center, three-period, crossover study. Eighteen asymptomatic, HIV-positive men were assigned randomly to 6 different sequences of 3 regimens: ddI (200 mg every 12 hours) alone for 4 days, ritonavir (600 mg every 12 hours) alone for 4 days, and 4 days of ddI with ritonavir under dose-staggering conditions. Although not statistically significant, ritonavir concentrations were slightly higher on average (<10%) with concurrent administration of ddI compared with those of ritonavir alone. In contrast, ddI concentrations were lower with concurrent administration compared with those of ddI alone; maximum concentration and area under the concentration-time curve were reduced by about 15% (p < .05). The ddI elimination rate constant was unaffected by ritonavir, suggesting no change in ddI's systemic metabolism. Adverse events were similar between regimens. The relatively minor changes in ritonavir and ddI pharmacokinetics are probably not clinically relevant; therefore, dosage adjustment of either compound appears unnecessary when administered concurrently. However, the combination regimen of ddI and ritonavir continue to be evaluated clinically. 相似文献
493.
RI Simon 《Canadian Metallurgical Quarterly》1998,26(3):361-374
The forensic psychiatrist must be able to perform a credible psychiatric evaluation and render a competent psychiatric opinion in hotly contested multiple chemical sensitivity (MCS) litigation. Forensic psychiatrists are often requested to evaluate MCS claimants by third party payers, employers, lawyers, and government agencies regarding health care costs and disability payments, workers' compensation claims, unemployment benefits, workplace accommodation reimbursements for special housing and environmental needs, civil litigation, and other claims. The credible forensic psychiatric evaluation of MCS litigants is described using the multiaxial diagnostic system of DSM-IV. Forensic psychiatrists must avoid becoming polarized by the current MCS controversy. The ethical requirements of honesty and striving for objectivity can be met by keeping separate the roles of therapist and expert, staying abreast of the scientific literature regarding MCS, and understanding the role of the psychiatric expert in MCS litigation. 相似文献
494.
495.
A prospective randomized study of 542 injured workers with continuing pain compared 271 workers who were treated at either one of two clinics that provided functional restoration with a control group of 271 subjects. Chronic pain was caused by low back injury in 78% of patients; 79% of those treated were at work 12 months after completion of treatment compared with 78% of the control subjects. When the patients were divided into subsets, based on the accident date and followed monthly, the duration of absence from work, the compensation costs, the disability award costs, and the total costs were less for those treated than the control subjects, but these were not statistically significant. Using the difference in total costs as a measure of relative success, back injuries had better results than other injuries in this study. 相似文献
496.
Twenty-four splenectomized dogs were subjected to rapid right ventricular pacing (RRVP) at 250 beats/min for five weeks. During the final three weeks, four groups six dogs were untreated or treated with captopril alone, with the angiotensin II type 1 (AT1) receptor antagonist L158,809 alone or with the two drugs combined by constant intravenous infusion. Hemodynamic studies were carried out during light anesthesia at baseline, and after two and five weeks of pacing. Total vascular capacitance and stressed blood volume were calculated from the mean circulatory filling pressure during transient circulatory arrest after acetylcholine administration at three different circulating volumes. Central blood volume and cardiac output were measured by thermodilution. Severe heart failure was present in the untreated group after five weeks of RRVP, characterized by low cardiac output and total vascular capacitance, high right atrial and pulmonary capillary wedge and mean circulatory filling pressure, plus increased stressed and central blood volumes. While L158,809 had not effect, captopril alone or combined with L158,809 ameliorated the reduction in total vascular capacitance, and reduced right atrial and mean circulatory pressure and stressed blood volumes. Combined therapy reduced pulmonary capillary wedge pressure. Thus, angiotensin-converting enzyme inhibition with captopril was effective in this model of chronic low output heart failure, whereas AT1 receptor antagonism was not. 相似文献
497.
RI Monsalve MA González de la Pe?a C López-Otín A Fiandor C Fernández M Villalba R Rodríguez 《Canadian Metallurgical Quarterly》1997,27(7):833-841
BACKGROUND: Seed proteins have been found to cause hypersensitivity by ingestion or inhalation. Rapeseed flour was responsible for allergic symptoms in a patient, who develops into allergy to mustard spice. OBJECTIVE: To determine the presence of allergenic proteins in rapeseed flour, and analyse the structure of the main component and its crossreactivity with the mustard allergen. METHODS: SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) and subsequent immunoblotting with a serum from a rapeseed allergic patient were performed to detect IgE-binding proteins. Proteolytic digestions and high performance liquid chromatography were used to obtain the peptides from the allergenic BnIII napin from rapeseed flour. Automatic Edman degradations were carried out to determine their amino acid sequences, which were compared with other sequences in nucleotide and amino acid sequence databases. Crossreactivity assays were carried out by ELISA inhibition using sera from a rapeseed allergic patient and from patients allergic to mustard. RESULTS: The 2S albumins of rapeseed were recognized by the serum from a patient allergic to this seed. The most abundant isoform of the allergenic napins, BnIII, was used for structural and immunological analysis. The protein consists of two different chains of 9.5 and 4.5 kDa. Their complete amino acid sequences were determined. The protein exhibited structural relationships with other napin-like storage proteins from seeds. IgE and IgG crossreactivity between rapeseed and mustard allergens was also demonstrated. Considering the structural and immunological data, certain polypeptide regions are suggested to be involved in the allergenicity of these proteins. CONCLUSIONS: Rapeseed contains 2S storage proteins which may cause allergy in hypersensitive individuals. These proteins exhibit great sequence similarity with 2S albumins from different seeds. Crossreactivity between mustard and rapeseed flours can be explained by sequence homology. 相似文献
498.
JJ Doski HS Heiman RI Solenberger RM Stefko T Kuivila TA Rozanski CA Flack RT Thurman CT Milbourn HW Cheu 《Canadian Metallurgical Quarterly》1997,32(12):1761-1766
The authors report the successful delivery, preoperative management, and postoperative courses of ischiopagus tripus twin girls successfully separated at 5 months of age. Surgical objectives were predicated on survival and optimum postseparation reconstructive potential for both girls. Each twin has subsequently undergone additional procedures, and both are doing well 2 years after separation. The authors reviewed 17 known cases of ischiopagus tripus separation, comparing anatomic findings, use of the tripus limb, operative strategies, and attainment of abdominal closure. This 18th case includes the first report of splitting the tripus limb and giving each girl a femur. The authors found that detailed systemic investigation, advanced coordinated teamwork with appropriate technical support, applications of new technologies or reapplication of existing technologies, meticulous planning, and favorable anatomy were vital in yielding favorable outcomes. 相似文献
499.
An African student developed bilateral relapsing iridocyclitis with increased intraocular pressure. General examinations and parasitological studies revealed tropical malaria. Etiotropic and local therapy normalized intraocular pressure and improved vision acuity of both eyes. This case should be borne in mind by general practitioners as a possibility of transportation of various tropical diseases. 相似文献
500.
RI Hidalgo-Laos A Kedar CA Williams RE Neiberger 《Canadian Metallurgical Quarterly》1997,11(5):645-648
A 12-year-old boy was referred because of abdominal pain, gross hematuria, and passage of stones. Further evaluation showed growth delay, low average range of intellectual functioning, and a speech articulation disorder. No signs of self-mutilation or self-injurious behavior were present. He had hyperuricemia, hyperuricosuria, uric acid crystalluria, uric acid calculi, macrocytosis, megaloblastic bone marrow changes, and mild anemia. Hypoxanthine phosphoribosyltransferase (HPRT) enzyme activity was reduced to approximately 26% of normal. Polymerase chain reaction-single strand conformational polymorphism analysis of the HPRT gene in DNA isolated from the patient's blood lymphocytes revealed a single nucleotide substitution at codon 200 in exon 8. The base change was a guanine to cytosine transversion, resulting in the conservative amino acid substitution of threonine in place of arginine. To our knowledge, this mutation has not previously been reported. 相似文献