Risk-stratified nosocomial infection surveillance in a neonatal intensive care unit: Report on 24 months of surveillance

Objective : To document the nosocomial infection rate in a single neonatal intensive care unit (NICU) in terms of patient workload and device utilization.
Methodology : Nosocomial infections have been identified and documented by the methodology described by the National Nosocomial Infection Surveillance System (NNIS), Centres for Disease Control, Atlanta. In addition, antibiotic usage has been surveyed in the NICU and standardized measures of patient exposure to antibiotics stratified by birthweight and gestational age have been described.
Results : Overall nosocomial infection rates compared favourably with the published NNIS figures at 6.2 infections per 100 admissions or 4.8 per 1000 patient days. Infection rates were significantly higher in lower birthweight groups. Device-related infection rates in each birthweight cohort were also very close to published figures and varied less with birthweight group. Antibiotic exposure averaged 12% of total admission days, less than previously published data.
Conclusions : The NNIS system is applicable to Australian NICU and provides an effective tool for monitoring infection episodes.     

The major determinant of exendin-4/glucagon-like peptide 1 differential affinity at the rat glucagon-like peptide 1 receptor N-terminal domain is a hydrogen bond from SER-32 of exendin-4

BACKGROUND AND PURPOSE

Exendin-4 (exenatide, Ex4) is a high-affinity peptide agonist at the glucagon-like peptide-1 receptor (GLP-1R), which has been approved as a treatment for type 2 diabetes. Part of the drug/hormone binding site was described in the crystal structures of both GLP-1 and Ex4 bound to the isolated N-terminal domain (NTD) of GLP-1R. However, these structures do not account for the large difference in affinity between GLP-1 and Ex4 at this isolated domain, or for the published role of the C-terminal extension of Ex4. Our aim was to clarify the pharmacology of GLP-1R in the context of these new structural data.

EXPERIMENTAL APPROACH

The affinities of GLP-1, Ex4 and various analogues were measured at human and rat GLP-1R (hGLP-1R and rGLP-1R, respectively) and various receptor variants. Molecular dynamics coupled with in silico mutagenesis were used to model and interpret the data.

KEY RESULTS

The membrane-tethered NTD of hGLP-1R displayed similar affinity for GLP-1 and Ex4 in sharp contrast to previous studies using the soluble isolated domain. The selectivity at rGLP-1R for Ex4(9–39) over Ex4(9–30) was due to Ser-32 in the ligand. While this selectivity was not observed at hGLP-1R, it was regained when Glu-68 of hGLP-1R was mutated to Asp.

CONCLUSIONS AND IMPLICATIONS

GLP-1 and Ex4 bind to the NTD of hGLP-1R with similar affinity. A hydrogen bond between Ser32 of Ex4 and Asp-68 of rGLP-1R, which is not formed with Glu-68 of hGLP-1R, is responsible for the improved affinity of Ex4 at the rat receptor.     

Multiple primary malignancies in patients with Merkel cell carcinoma1

Background Merkel cell carcinoma (MCC) is a rare malignant cutaneous tumour, the incidence of which is increasing. Second malignancies have been reported to occur with high incidence in these patients. Objectives We report the rate and nature of multiple malignancies in patients with MCC treated over a 10 year period in Addenbrooke’s Hospital in Cambridge, United Kingdom, as well as the temporal relationship of these additional malignancies to the diagnosis of MCC. Results The 27 patients had an approximately equal sex incidence with a median age at diagnosis of 79 years. Seventy percent (n=19) of patients had a second primary malignant tumour; and 7 of these patients had two or more tumours in addition to the MCC. Eighteen patients had additional cutaneous malignancies: melanoma, squamous cell carcinoma and basal cell carcinoma, and 8 patients presented non‐cutaneous malignancy including colorectal, haematological and breast tumours. Of the 28 additional tumours in our patients, half were diagnosed prior to presentation of MCC, 32% within 6 months of diagnosis, and 18% between 6 months and 3 years after diagnosis. Possible reasons for the high rate of additional tumours in this population are discussed. Conclusions Our figures reflect a higher incidence of multiple malignancies in those with Merkel cell tumour than has previously been reported. This has important implications for the care and surveillance of these patients.     

Malignant jejunal strictures after Whipple procedure: stenting with large-bore tubes and use of combined transhepatic and peroral approach

Malignant strictures of the afferent jejunal limbs are difficult to treat. Surgical revision and chronic external drainage, two commonly used palliative procedures, have significant associated morbidity. A combined transhepatic and peroral approach was used to stent malignant jejunal strictures in two patients, allowing antegrade internal drainage of biliary and pancreatic secretions. Excellent palliation was achieved, and there were no associated complications.     

超声和微泡造影剂介导细胞基因转染的实验研究

目的 探讨低频超声对细胞基因转染的作用。方法 超声治疗仪频率1MHz，脉冲重复频率100Hz，占空系数20％。质粒DNA为含编码绿荧光蛋白的pEGFP。应用荧光显微镜和流式细胞仪评价细胞基因转染率，台盼蓝染色计算细胞成活率。选用C2C12、3T3-MDEI和CHO3种细胞系为研究对象，加入DNA后辐照不同声强、时间或加入超声造影剂，观察各条件下的细胞基因转染率和成活率。结果 ①超声介导的基因转染与声强和辐射时间有关，最佳剂量为1w／cm^2 20s；②同样超声剂量，较高的声强较早达到最大基因转染率；③较低剂量时，微泡造影剂可使超声介导的基因转染提高2～3倍并可显著提高最高基因转染率。结论 低频超声可介导细胞基因转染，基因转染率不但与超声辐射剂量有关，而且同样剂量时，高声强较早达到最大基因转染率，最佳剂量是1w／cm^2 20s。同时，微泡造影剂可提高超声介导基因转染的最高转染率。     

无牙颌颞下颌关节紊乱病患者总义齿修复前后咬合垂直距离改变与髁状突在关节凹内位置的关系

目的:观察咬合垂直距离改变对无牙颌颞下颌关节紊乱病患者两侧颞颌关节髁状突位置的影响。方法:于1994-01/1997-12选择本院口腔修复门诊收治的无牙颌患者中符合颞下颌关节紊乱病诊断标准,同时垂直距离减低的患者48例。实验方案经医院伦理委员会审批,患者均知情同意。将48例无牙颌颞下颌关节紊乱病患者根据垂直距离减低程度的不同分为3组:减低1.8～6.0mm组18例,减低6.1～10.0mm组20例,减低10.1￣14.0mm组10例。通过重新制作一副全口义齿的方法治疗,咬合垂直距离恢复在合适的范围内,3组全口义齿的咬合垂直距离恢复前分别平均为63.4,60.6,54.2mm,恢复后咬合垂直距离分别平均为67.8,68.4,66.4mm,平均抬高4.4,7.8,12.2mm。通过拍摄正中颌位时颞下颌关节薛氏位X射线片测量各组前、后、上关节间隙。结果:垂直距离恢复前,减低1.8～6.0mm组关节后间隙,减低6.1～10.0mm组关节前、后间隙、减低10.1￣14.0mm组关节上、后间隙左右侧相比较,差异有显著性意义(P<0.05)。垂直距离恢复后,3组关节间隙左右侧差异无显著性意义。结论:无牙颌咬合垂直距离减低后可以导致两侧髁状突位置发生不对称改变。     

脑出血大鼠脑组织膜型基质金属蛋白酶、基质金属蛋白酶2和基质金属蛋白酶9表达及益气活血中药的干预效应

目的:观察益气活血中药对脑出血大鼠脑组织中膜型基质金属蛋白酶、基质金属蛋白酶2和基质金属蛋白酶9表达量的影响,从脑出血损伤区微血管系统重建的角度,探讨益气活血中药治疗脑出血的作用机制。方法:实验于2006-03/10在中南大学湘雅医院中西医结合研究所实验室完成。实验材料:补阳还五汤全方(黄芪,当归,赤芍,红花,川芎,地龙,桃仁按20∶3∶3∶3∶2∶3∶3的比例);补阳还五汤益气成分(黄芪按上述比例);补阳还五汤活血成分(当归,赤芍,地龙,川芎,桃仁,红花按3∶3∶3∶2∶3∶3的比例)。用蒸馏水两次水煎,分别浓缩为1.54,0.81和0.73g/mL。实验分组:155只SD大鼠随机分为正常对照组、假手术组、模型组、益气活血组、益气组、活血组。正常对照组5只大鼠,其余每组30只,再随机分为术后灌胃2,4,7,14,21,28d6个观察时间点,各个时间点5只大鼠。实验干预:造模:采用立体定位技术将胶原酶Ⅶ注入大鼠大脑右苍白球制成脑出血大鼠模型。假手术组大鼠仅注入2μL生理盐水,其余手术过程相同。给药:正常对照组:普通饲养,自由饮水;假手术组和模型组术后予蒸馏水灌胃2次/d,2mL/次;益气活血组、益气组、活血组分别给予补阳还五汤全方、补阳还五汤益气成分、补阳还五汤活血成分30.80,16.20,14.60g/(kg·d)(按体表面积计算为临床70kg成人剂量的3倍)灌胃,2次/d,2mL/次。各组大鼠分别于灌胃2,4,7,14,21,28d麻醉下取脑,制备切片;正常组动物于28d处死。实验评估:免疫组织化学染色方法检测各组灌胃不同时间脑组织基质金属蛋白酶2、基质金属蛋白酶9和膜型基质金属蛋白酶的阳性微血管数。结果:155只大鼠均进入结果分析。①正常组、假手术组皮质偶见膜型基质金属蛋白酶、基质金属蛋白酶2和基质金属蛋白酶9表达。②模型组膜型基质金属蛋白酶、基质金属蛋白酶2呈双峰表达,4d为最高峰,至14～21d再有小高峰出现。③益气活血组给药4d时,膜型基质金属蛋白酶、基质金属蛋白酶2为表达低谷,低于模型组(P<0.01)、益气组和活血组(P<0.05);在中后期,益气活血组膜型基质金属蛋白酶表达高峰为7～14d,较模型组提前出现,21d后与模型组比,各治疗组膜型基质金属蛋白酶已表达极少(P<0.01);益气活血组基质金属蛋白酶2在7d后一直呈高水平维持,高于其他各组(P<0.05),28d后开始逐渐下降。④模型组基质金属蛋白酶9在造模后4d达最高峰(P<0.01),两周后几乎无表达。益气活血组基质金属蛋白酶9高峰推迟至7d出现(P<0.05),之后逐渐下降。结论:益气活血中药可通过调节脑出血后膜型基质金属蛋白酶、基质金属蛋白酶2和基质金属蛋白酶9表达,改善出血后脑组织的微环境,有利于微血管系统重建,促进组织修复。     

Factors predictive of response and survival in patients with metastatic colorectal cancer in Taiwan

5-Fluorouracil in combination with leucovorin has been shown to be active in therapeutic trials of metastatic colorectal carcinoma. In this study, we administered these drugs to 72 patients with metastatic colorectal carcinoma. Thirty-six of them without previous exposure to 5-fluorouracil were treated with weekly bolus injections of 5-fluorouracil (425 mg/m2) and leucovorin (25 mg/m2) supplemented with oral levamisole. Another 36 patients with or without prior 5-fluorouracil treatment received 5-fluorouracil 3,000 mg/m2 and leucovorin 300 mg/m2 in a 48-hour continuous infusion every two weeks. Clinical efficacy and toxicity were assessed by WHO criteria. Variables were tested for relations to response and survival by univariate and multivariate analysis. The response rate was 19.4% in weekly bolus arm and 13.9% in biweekly high-dose infusion arm (P = 0.527). Median survivals in the two arms were 18.4 months (weekly) and 21 months (biweekly) respectively (P = 0.708). Gastrointestinal side effects including nausea, vomiting, diarrhea and mucositia were the major toxicities of these regimens. By multivariate analysis, the only factor to influence response rate was the site of metastases (P = 0.009). The only factor to affect survival was performance status of the patient (P = 0.0001). We concluded that the two 5-fluorouracil based regimens are well-tolerated and shown to have a response rate comparable with previous reports of similar regimens in patients with metastatic colorectal cancer. Only liver metastases seemed to have a better response to therapy. Performance status is the most important prognostic factor in patients with metastatic colorectal cancer.