基于7次跨膜受体的药物发现基本方法——细胞检测

随着检测技术进步,含7个跨膜α螺旋结构的受体性质已渐为人们所了解。7次跨膜（7TM）受体不仅具有开关功能,更类似于信息微处理器;特定配体只能参与特定受体介导的部分信号机制,这就为药物发现开拓了一个新领域。为进一步发现7TM受体与配体间的新行为并量化评价药物对这一复杂系统的作用效能,进而指导药物化学研究,药理学检测已成为关注焦点。本文阐述从还原重组体到整体系统测定方法的回归,讨论药物效价与评价其效应的特定检测方法间的联系,强调新的检测方法在药物发现过程中的价值。     

Microalbuminuria in children with vesicoureteral reflux

Vesicoureteral reflux (VUR) is a common congenital anomaly of the urinary tract that may be inherited. Reflux of infected urine may cause scarring in susceptible kidneys with the potential to compromise renal function. The aim of the study was to evaluate the possible influence of different grades of VUR on glomerular damage using microalbuminuria as a parameter. Children with VUR detected by voiding cystourethrography (VCUG) were investigated. According to the grade of VUR, patients were separated into three groups. The first group included 12 children with VUR grade I-II. The second group consisted of 12 children with grade III of VUR. Patients with VUR grade IV-V (n = 11) were members of the third group. The control group consisted of 17 healthy children. Microalbuminuria was examined in samples of morning urine specimens using a microalbumin/creatinine reagent kit. Serum urea, creatinine levels and creatinine clearance (CCR) were measured as markers of renal function. The mean value of microalbumin excretion in the third group showed a statistically significant increase (p < 0.001) compared to all other groups. CCR in the third group was statistically significantly decreased (p < 0.05) in comparison to the group of healthy children. There were no statistically significant changes of microalbumin excretion and CCR in the first and second group compared to control values. We discussed the presence of microalbuminuria and decrease of CCR in children with high grade of VUR as a possible consequence of retrograde urine flow (intrarenal reflux), glomerulosclerosis, and consecutive hyperfiltration.     

Uterine artery embolization for symptomatic fibroids with imaging follow up

The aim of this study was to determine the effectiveness of uterine artery embolization (UAE) as a primary treatment method in treatment of symptomatic fibroids, whether there are any preembolization MRI characteristics of fibroid predictive of reduction in volume and assess reduction in uterine and dominant fibroid volumes using ultrasound (US) and MRI. Study was carried out in total of 32 patients aged 25–49 years (mean 40.9 years). Uterine and dominant fibroid volume were determined using US and MRI before UAE, MRI and US at 3 months and US alone at 6 and 12 months post‐UAE, supplemented by clinical evaluation at interval of 3, 6 and 12 months. Procedure was carried out through unilateral femoral puncture using poly vinyl alcohol (PVA) particles 355–500 μm in size. All 32 patients had successful procedures. Overall, 25 patients responded, giving a clinical success rate of 78.12%. Mean reduction in volume of uterus and fibroid was 33 and 59.7% and 48.9 and 75.5% on US at 3 and 12 months respectively, and 33.3 and 58.6% on MRI at 3 months. Volume reduction on US and MRI at 3 months was highly correlative. There was no statistical difference in size reduction in volume of fibroids, which were hypointense or hyperintense on T2‐weighted image (T2WI) on pre‐UAE MRI. Uterine artery embolization leads to good technical success and fibroid volume reduction. Ultrasound alone may be used for follow up of patients post‐UAE. Preprocedure signal characteristics on T2WI are not predictors of volume reduction after UAE.     

Pancreaticoduodenectomy with vascular reconstruction for adenocarcinoma of the pancreas with borderline resectability

AIM: To analyze whether pancreaticoduodenectomy with simultaneous resection of tumor-involved vessels is a safe approach with acceptable patient survival.METHODS: Between January 2001 and March 2012, 136 patients received pancreaticoduodenectomy for adenocarcinoma at our hospital. Seventy-eight patients diagnosed with pancreatic head carcinoma were included in this study. Among them, 46 patients received standard pancreaticoduodenectomy (group 1) and 32 patients received pancreaticoduodenectomy with simultaneous resection of the portal vein or the superior mesenteric vein or artery (group 2) followed by reconstruction. The immediate surgical outcomes and survivals were compared between the groups. Fifty-five patients with unresectable adenocarcinoma of the pancreas without liver metastasis who received only bypass operations (group 3) were selected for additional survival comparison.RESULTS: The median ages of patients were 67 years (range: 37-82 years) in group 1, and 63 years (range: 35-86 years) in group 2. All group 2 patients had resection of the portal vein or the superior mesenteric vein and three patients had resection of the superior mesenteric artery. The pancreatic fistula formation rate was 21.7% (10/46) in group 1 and 15.6% (5/32) in group 2 (P = 0.662). Two hospital deaths (4.3%) occurred in group 1 and one hospital death (3.1%) occurred in group 2 (P = 0.641). The one-year, three-year and five-year overall survival rates in group 1 were 71.1%, 23.6% and 13.5%, respectively. The corresponding rates in group 2 were 70.6%, 33.3% and 22.2% (P = 0.815). The one-year survival rate in group 3 was 13.8%. Pancreaticoduodenectomy with simultaneous vascular resection was safe for pancreatic head adenocarcinoma.CONCLUSION: The short-term and survival outcomes with simultaneous resection were not compromised when compared with that of standard pancreaticoduodenectomy.     

双能量X线骨质密度测量仪监测小儿下肢骨延长骨矿物质的变化

目的　在儿童骨延长的患儿中 ,为了能够有效地控制骨延长的速率 ,达到骨延长的目的 ,采用双能量X线骨质密度测量仪 (dualenergyX Rayabsorptiometry ,DEXA)监测延长断端骨矿含量 (bonemineralcontent,BMC)的变化。方法　 30例患儿中有 5 0处下肢作了骨延长术 ,平均年龄10 .9岁 (5～ 17岁 ) ,引起短肢的病因不同。术后 7～ 10d开始行骨延长 ,每次延长 0 .2 5mm ,每天 4次。牵引延长期间每周扫描一次 ,拆除外固定器后每 2周扫描一次到术后 2年。DEXA扫描的分辨率是 1mm× 1mm ,扫描速度 30mm/s。比较不同延长时期中骨矿含量的变化。分析不同病因和不同外固定器之间骨矿含量变化的差别。结果　不同固定器之间骨矿含量的差别无著性意义。根据骨延长区BMC增加速率 ,将患儿分为快速组、一般组和慢速组。快速组每日BMC增加速率为 0 .3%～ 0 .6 % ,新骨生长快速 ;一般组每日BMC增加 0 .1%～ 0 .3% ,新骨中速生长 ;慢速组每日增加 <0 .1% ,新骨生成缓慢。骨矿化速率与原发病因相关。结论　DEXA能动态监测骨延长中新生骨的骨矿含量的变化 ,根据骨矿含量变化的程度 ,能够调整骨延长的速率 ,从而达到预期骨延长的目的。     

Emergency embolization of spontaneous ruptured hepatocellular carcinoma: Correlation between survival and Child−Pugh classification

From February 1994 to April 2000, 29 emergency gelfoam embolizations for spontaneous ruptured hepatocellular carcinoma (HCC) performed in 28 patients were retrospectively reviewed. There were 11 patients in Child's A , 11 in Child's B and six in Child's C classification of cirrhosis. The duration of the procedure, artery embolized and complications were reviewed, and the Child?Pugh classification of each patient was correlated with their mean survival period. Embolization was done in 12 right hepatic arteries, two left hepatic arteries and 15 proper hepatic arteries. In one patient, the left hepatic artery was embolized initially but the proper hepatic artery was also embolized because another subcapsular liver tumour was found after reviewing the preangiogram CT scan. The entire procedure took 40?170 min (mean = 86 min) with no periprocedural complication. Following embolization, the mean survival period for Child's A class was 218.3 days, Child's B class was 83.4 days and Child's C class was 11.0 days. Transcatheter embolization is an effective treatment to arrest bleeding in spontaneous ruptured HCC. Patients with Child's A class cirrhosis have the longest survival. Selective embolization of either the right or the left hepatic artery alone carries the potential risk of missing multifocal HCC that might not be easily appreciated during angiography.     

Comparison of the effects of continuous and pulsed mobile phone like RF exposure on the human EEG

It is not clear yet whether Global System for Mobiles (GSM) mobile phone radiation has the ability to interfere with normal resting brain function. There have been reports that GSM exposure increases alpha band power, and does so only when the signal is modulated at low frequencies (Huber, R., Treyer, V., Borbely, A. A., Schuderer, J., Gottselig, J. M., Landolt, H.P., Werth, E., Berthold,T., Kuster, N., Buck, A and Achermann, P. Electromagnetic fields, such as those from mobile phones, alter regional cerebral blood flow and sleep and waking EEG. J Sleep Res 11, 289-295, 2002.) However, as that research employed exposure distributions that are not typical of normal GSM handset usage (deep brain areas were overexposed), it remains to be determined whether a similar result patterning would arise from a more representative exposure. In this fully counterbalanced cross-over design, we recruited 12 participants and tried to replicate the modulation linked post exposure alpha band power increase described above, but with an exposure source (dipole antenna) more closely resembling that of a real GSM handset. Exposures lasted for 15 minutes. No changes to alpha power were found for either modulated or unmodulated radiofrequency fields, and thus we failed to replicate the above results. Possible reasons for this failure to replicate are discussed, with the main reason argued to be the lower and more representative exposure distribution employed in the present study. In addition we investigated the possible GSM exposure related effects on the non-linear features of the resting electroencephalogram using the Approximate Entropy (ApEn) method of analysis. Again, no effect was demonstrated for either modulated or unmodulated radiofrequency exposures.     

OFLOXACIN VERSUS TRIMETHOPRIM AND CO-TRIMOXAZOLE IN THE TREATMENT OF UNCOMPLICATED URINARY TRACT INFECTION IN GENERAL PRACTICE

A large-scale, randomised, multicentre single-blind clinical trial was conducted to assess the comparative efficacy and tolerance of ofloxacin, trimethoprim and co-trimoxazole in the treatment of uncomplicated urinary tract infection in general practice. A total of 1,069 patients from 76 centres across the UK were enrolled in the study, and randomised to one of the following treatment groups: ofloxacin (200 mg od), trimethoprim (200 mg bd) or co-trimoxazole (trimethoprim 160 mg and sulphamethoxazole 800 mg bd). Each patient received five days of medication. Clinically, ofloxacin was as effective as trimethoprim and co-trimoxazole. However, the bacteriological cure rate was significantly better for ofloxacin, with eradication of the initial causative pathogen by the end of treatment in 92% of patients in the ofloxacin group, compared with 81% for trimethoprim and co-trimoxazole (P = 0.0002). There was also a lower relapse rate for ofloxacin. Ofloxacin was well tolerated: adverse events were reported by 67 (12.4%) patients in the ofloxacin group, compared with 48 (18.7%) patients in the co-trimoxazole group and 37 (13.6%) patients in the trimethoprim group. Ofloxacin can therefore be considered a suitable alternative for the treatment of uncomplicated urinary tract infection.