Optimal metabolite curve fitting for kinetic modeling of 11C-WAY-100635.

Many quantitative imaging protocols that make use of a metabolite-corrected arterial input function require the use of a mathematic model to describe the rate of metabolism of the radioligand. Commonly, parametric models are fit to metabolism data and then the fitted model is used to correct the plasma input function. (11)C-WAY 100635 is a rapidly metabolized radioligand used extensively in mapping the 5-hydroxytryptamine receptor 1A system. METHODS: To evaluate the adequacy of fit of 4 metabolite models, we examined data from 92 subjects who received an injection of (11)C-WAY 100635, were imaged with PET, and underwent measurement of total plasma concentration and metabolites. The performance of these models was assessed according to residual plots, as well as fit and information criteria. RESULTS: The study showed that the choice of model has a substantial effect on the resulting estimates of outcome measures. CONCLUSION: Among the models considered, the Hill model provides the best fit across all criteria.     

458例尿路结石成分分析

目的 探讨西安地区尿路结石的成分状况，为临床防治提供帮助。方法对458例尿路结石标本进行化学成分测定，并结合临床资料进行比较。结果尿路结石男性发病多于女性，男、女比为2．1：1，20一50岁为高发年龄，上尿路结石明显多于下尿路结石，上、下尿路结石之比为10．5：1。结石成分以混合结石占多数，为325例（71％），其中以草酸钙，磷酸钙与尿酸的混合结石为主。对比混合性结石及单纯性结石发现，各种成分所占比例基本一致。结论结石成分分析对于了解结石成因、预防结石形成和复发具有重要的意义。     

肥大肝叶内胆管结石的处理

目的探讨在肝肥大-萎缩征中肥大肝叶内胆管结石的处理方法。方法回顾性分析我科1990年6月～2004年12月收治的103例肥大肝叶内胆管结石病人的临床资料，总结其手术治疗的原则和方法。结果全体病例均经手术治愈，术后残石率17．5％，效果优良率83．7％。结论肥大肝叶内的胆管结石，手术难度大，应根据病情选择手术方式，既要遵循肝胆管结石的治疗原则，又要保护赖以生存的肥大肝叶（段）。     

益肝灵保护大鼠肾缺血再灌注损伤的实验研究

目的探讨益肝灵对肾缺血再灌注损伤的保护作用。方法建立肾缺血再灌注模型，大鼠右肾切除，左侧肾蒂夹闭45min后再灌60min。用益肝灵预防性治疗，检测并比较肾组织及血清中MDA及SOD的活性变化。结果益肝灵能明显押制缺血再灌所致的血及肾组织中MDA的升高和SOD的活性降低。结论益肝灵对肾缺血再灌注损伤具有保护作用。     

Growth hormone effects on hypertrophic scar formation: a randomized controlled trial of 62 burned children

The hypercatabolism after massive pediatric burns has been effectively treated with recombinant human growth hormone, an anabolic agent that stimulates protein synthesis and abrogates growth arrest. While experimental studies have shown increased potential for fibrosis induced by growth hormone therapy, adverse effects on human scars have not been investigated. Our aim was to evaluate hypertrophic scar formation in 62 patients randomized to receive injections of 0.05 mg/kg/day of recombinant human growth hormone or placebo, from discharge until 1 year after burn. Scar scales were used to evaluate scar-severity at discharge, 6, 9, 12, and 18-24 months after burn, by three observers blinded to treatment. Computer-assisted planimetry allowed quantification of percentage of hypertrophic scar formation. Types I and III collagens were localized and quantified in scars and normal skin of patients from both groups, using immunohistochemistry with confocal laser microscopy analysis. Insulin-like growth factor-1 blood levels helped assess compliance. Statistical analysis showed that scar hypertrophy significantly increased from 6 to 12 months after injury in both groups, while decreasing at 18-24 months postburn. Types I and III collagens were statistically increased in the reticular layer of scars from both groups when compared to paired normal skin. Insulin-like growth factor-1 was significantly increased in the recombinant human growth factor-treated group. No differences were seen when recombinant human growth factor and control groups were compared using the scar scales, planimetry, or immunohistochemistry. We concluded that recombinant human growth hormone therapy did not adversely affect scar formation and should not contraindicate the administration of recombinant human growth hormone as a therapeutic approach to severely burned children.     

Disposition of tacrolimus in isolated perfused rat liver: influence of troleandomycin, cyclosporine, and gg918.

The disposition of tacrolimus and the influence of cyclosporine, troleandomycin, and GF120918 (GG918, or N-[4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)-ethyl]-phenyl]-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamine) on its hepatic disposition were examined in the isolated perfused rat liver. Livers from groups of rats were perfused in a recirculatory manner following a bolus dose of tacrolimus (100 microg), a substrate for P-glycoprotein (P-gp) and CYP3A, or with felodipine (200 microg), a substrate only for CYP3A. Perfusions of each substrate were also examined in groups of rats in the presence of the inhibitors: troleandomycin (20 microM, CYP3A inhibitor), GG918 (1 microM, P-gp inhibitor), or cyclosporine (10 microM, CYP3A and P-gp inhibitor). In all experiments, perfusate and bile were collected for 60 min. Tacrolimus, felodipine, and their primary metabolites were determined in perfusate and bile by liquid chromatography/tandem mass spectrometry. The area under the curve (AUC) from 0 to 30 min was determined. For the dual CYP3A and P-gp substrate, tacrolimus, AUC +/- S.D. was decreased from control (2,260 +/- 430 ng. min/ml) by GG918 (1,730 +/- 270 ng. min/ml, P < 0.05) and was increased by troleandomycin (5,200 +/- 2,470 ng. min/ml, P < 0.05) and cyclosporine (4,390 +/- 2,080 ng. min/ml, P < 0.05). For the exclusive CYP3A substrate, felodipine, AUC was unchanged from control by GG918 but increased by troleandomycin and cyclosporine. It is concluded that GG918 increased the hepatic exposure of tacrolimus by inhibiting the canalicular P-gp transport, whereas GG918 has no effect on hepatic disposition of felodipine. These results support our hypothesis that the hepatic metabolic clearance of a dual substrate will be increased by inhibiting the efflux transporter.     

AN-132 block of cardiac sodium channels: A gate-related receptor analysis

Summary Based on the gate-related receptor hypothesis, an analysis of kinetics of AN-132, a new antiarrhythmic agent, blockade of cardiac sodium channels and the gate-related receptor which is bound by the drug was performed by computer simulation. Model-predicted apparent rates of onset of AN-132 (30 μmol/L) blocking were 0.051, 0.038, and 0.034 AF⁻¹ at stimulation frequencies of 1.0, 2.0 and 3.0 Hz, respectively. The time constant of recovery from block by AN-132 at resting potential -90 mV was 39.5 s. These findings are in agreement with those experimental data documented. The analysis of gate-related receptor shows that AN-132 binds the inactivation gate-related receptor, and the binding and unbinding are modulated by the inactivation process.     

脊髓血管畸形合并胸腔血管畸形

脊髓血管畸形的临床发病率较低,仅为颅内血管畸形或脊髓新生物的1/10左右.本病可能与其它组织的血管异常同时存在,如皮肤血管痣(Cobb综合征),皮肤、粘膜病变,和Klipple-Trenaunay-Weber综合征等.本文报告的与胸腔血管畸形同时存在的脊髓血管畸形,我们尚未见诸报道.本文还结合文献就脊髓血管畸形导致脊髓功能损害的病理生理作了阐述.     

人细胞色素p450IA1基因cDNA的克隆和鉴定

在用３－甲基胆蒽诱导培养人羊膜ＦＬ细胞２４ｈ后，抽提细胞总ＲＮＡ并直接合成ｃＤＮＡ第一链。利用人工合成的一对寡核苷酸引物，采用ＰＣＲ技术特异性地扩增Ｃｙｔ ｐ５０ＩＡ１ ｃＤＮＡ。３０个循环后琼脂糖凝胶电泳显示１．５Ｋｂ大小片段，长度与预计相符。Ｓｏｕｔｈｅｒｎ杂交结果证实此片段确为Ｃｙｔ ｐ４５０ＩＡ１ ｃＤＮＡ。将此片段克隆至质粒ｐＧＥＭ－３Ｚ并进行部份序列分析。结果显示克隆片段包含Ｃｙｔ ｐ     

A型肉毒杆菌毒素治疗麻痹性斜视

采用眼外肌注射A型肉毒杆菌毒素的方法,治疗17例(18只眼)麻痹性内斜视患者。最大的肌肉麻痹作用发生于注射后7～14天,最大斜视矫正度为50-,随访时间为4～20周,5例最终获得双眼视。未见全身副作用。认为,这种疗法可在部分患卉中替代斜视矫正术。