The effect of diabetes mellitus on the association between measures of glycaemic control and ICU mortality: a retrospective cohort study

Introduction

In critical illness, four measures of glycaemic control are associated with ICU mortality: mean glucose concentration, glucose variability, the incidence of hypoglycaemia (≤ 2.2 mmol/l) or low glucose (2.3 to 4.7 mmol/l). Underlying diabetes mellitus (DM) might affect these associations. Our objective was to study whether the association between these measures of glycaemic control and ICU mortality differs between patients without and with DM and to explore the cutoff value for detrimental low glucose in both cohorts.

Methods

This retrospective database cohort study included patients admitted between January 2004 and June 2011 to a 24-bed medical/surgical ICU in a teaching hospital. We analysed glucose and outcome data from 10,320 patients: 8,682 without DM and 1,638 with DM. The cohorts were subdivided into quintiles of mean glucose and quartiles of glucose variability. Multivariable regression models were used to examine the independent association between the four measures of glycaemic control and ICU mortality, and for defining the cutoff value for detrimental low glucose.

Results

Regarding mean glucose, a U-shaped relation was observed in the non-DM cohort with an increased ICU mortality in the lowest and highest glucose quintiles (odds ratio = 1.4 and 1.8, P < 0.001). No clear pattern was found in the DM cohort. Glucose variability was related to ICU mortality only in the non-DM cohort, with highest ICU mortality in the upper variability quartile (odds ratio = 1.7, P < 0.001). Hypoglycaemia was associated with ICU mortality in both cohorts (odds ratio non-DM = 2.5, P < 0.001; odds ratio DM = 4.2, P = 0.001), while low-glucose concentrations up to 4.9 mmol/l were associated with an increased risk of ICU mortality in the non-DM cohort and up to 3.5 mmol/l in the DM cohort.

Conclusion

Mean glucose and high glucose variability are related to ICU mortality in the non-DM cohort but not in the DM cohort. Hypoglycaemia (≤ 2.2 mmol/l) was associated with ICU mortality in both. The cutoff value for detrimental low glucose is higher in the non-DM cohort (4.9 mmol/l) than in the DM cohort (3.5 mmol/l). While hypoglycaemia (≤ 2.2 mmol/l) should be avoided in both groups, DM patients seem to tolerate a wider glucose range than non-DM patients.     

卵胞质移植、克隆与逆向克隆

目的:最近人类卵细胞间的胞质移植被作为人类辅助生殖生物技术的手段并成为研究热点。本文回顾了该领域的研究进展和存在的问题,并以此为基础提出“逆向克隆技术”这一新概念。资料来源:应用计算机检索PUBMED 1998-01/2006-12期间的相关文章,检索词为“ooplasmic transfer,mitochondria heteroplasmy,animal cloning”,并限定文章语言种类为English。同时计算机检索万方数据库1998-01/2006-12期间的相关文章,检索词为“胞质转移,线粒体异质性,动物克隆”,并限定文章语言种类为中文。资料选择:对资料进行初审,并查看每篇文献后的引文。纳入标准:文章所述内容应与卵胞质移植、克隆或逆向克隆研究相关。排除标准:重复研究或Meta分析类文章。资料提炼:共收集到126篇相关文献,31篇文献符合纳入标准,排除的95篇文献为内容陈旧或重复。符合纳入标准的31篇文献中,17篇涉及卵胞质移植,13篇涉及动物克隆,1篇涉及逆克隆。资料综合:人类的生殖技术领域发展迅速,卵胞质移植技术得到广泛应用。研究表明,卵胞质对受精和胚胎发育具有重要作用,其中线粒体与受精和胚胎发育关系最为密切。大量实验对细胞质与细胞核的相互作用、基因组的重编程机制上进一步研究,同时也在技术上不断改进。克隆技术有广阔的应用前景,同时也存在着不少问题,基于此提出以胞质转移为基础的“逆向克隆技术”。结论:线粒体对卵母细胞的受精和胚胎发育有显著影响,但卵胞质移植可能导致线粒体的异质性及其潜在的问题还需要进一步研究。以卵胞质转移为基础的“逆向克隆技术”是否能达到克隆动物的结果前景喜人。     

血管内皮生长因子对佐剂性关节炎滑膜细胞基质金属蛋白酶3及基质金属蛋白酶9表达的影响

目的:观察血管内皮生长因子对佐剂性关节炎滑膜细胞质金属蛋白酶3及质金属蛋白酶9表达的影响,并探讨其意义。方法:实验于2006-02/12在桂林医学院实验中心完成。①实验材料:清洁级8周龄雄性Wistar大鼠6只,血管内皮生长因子为Peprotech EC LTD公司产品,基质金属蛋白酶3(扩增369bp)上游引物、下游引物,基质金属蛋白酶9(扩增405bp)上游引物、下游引物均购自晶美公司。②实验干预:先用弗氏完全佐剂造Wistar大鼠模型;造模20d后取Wistar大鼠右后足滑膜细胞进行原代培养。③实验分组:实验分为血管内皮生长因子组:取P2代细胞接种于6孔培养板,分别加入终浓度为5,25,50μg/L血管内皮生长因子;对照组:不加血管内皮生长因子。④实验评估:取病理切片观察滑膜细胞形态学改变;采用半定量反转录聚合酶链反应检测Wistar大鼠佐剂性关节炎滑膜细胞基质金属蛋白酶3及基质金属蛋白酶9的m-RNA表达。结果:①培养细胞的形态学观察:原代培养14d滑膜细胞从组织块边缘逸出,21d密集生长开始传代;传代细胞48h可明显分辨出树突样细胞、巨噬细胞样细胞和成纤维细胞样细胞;传至21代,细胞生长及特性稳定。②病理切片:滑膜组织有中性粒细胞、单核细胞、淋巴细胞浸润,滑膜细胞增生、排列紊乱,纤维素渗出,胶原纤维沉着,纤维素样坏死,呈滑膜炎表现。③基质金属蛋白酶3、基质金属蛋白酶9的mRNA表达:对照组基质金属蛋白酶3mRNA表达相对灰度值与血管内皮生长因子终浓度5,25,50μg/L组比较,差异有显著性意义(0.32±0.03,0.77±0.06,1.12±0.12,1.59±0.02,P<0.05);对照组基质金属蛋白酶9mRNA表达相对灰度值与血管内皮生长因子终浓度5,25,50μg/L组比较,差异有显著性意义(0.47±0.07,0.50±0.10,0.91±0.10,1.31±0.06,P<0.05);基质金属蛋白酶3和基质金属蛋白酶9mRNA表达随血管内皮生长因子浓度的加大表达增加。结论:血管内皮生长因子以剂量递增的方式对体外培养的佐剂性关节炎滑膜细胞基质金属蛋白酶3及基质金属蛋白酶9的表达有促进作用。     

中国西南地区汉族人群肿瘤坏死因子基因多态性与鼻咽癌遗传易感性

目的:分析肿瘤坏死因子基因多态性分布与中国西南地区汉族人群鼻咽癌易感性的关系。方法:选择2000-10/2005-09在华西医科大学第一附属医院就诊的100例鼻咽癌患者为鼻咽癌组,均经过病理科活检确诊,其中包括未治疗44例,放疗后37例,放疗加化疗后19例,选择100名同期入院健康体检者为对照组。所有受试对象为中国西南地区汉族人,均对检测项目知情同意。采用聚合酶链反应-限制性片段长度多态性的方法检测100例中国西南地区汉族鼻咽癌患者和100名健康对照者肿瘤坏死因子α基因启动子区-308位点及肿瘤坏死因子β基因第一内含子252位点的等位基因以及基因型频率,分析两位点多态性与鼻咽癌遗传易感性的关系。结果:鼻咽癌组患者肿瘤坏死因子β( 252)位点G/A杂合子基因型频率显著高于对照组(57%,29%,P<0.01),野生型(G/G基因型)频率低于健康对照组(23%,51%,P<0.01),等位基因A的频率高于健康对照组(48.5%,13%,P<0.01);肿瘤坏死因子α(-308)位点基因型以及等位基因频率与对照组相比较无统计学差异。结论:本实验人群中未发现肿瘤坏死因子α(-308)位点多态性与鼻咽癌易感性无关;肿瘤坏死因子β( 252)位点基因多态性与鼻咽癌具有相关性,A等位基因可能是鼻咽癌的遗传易感基因,G/A杂合子基因型个体较易患鼻咽癌。     

Bcl-2蛋白表达与乳癌预后病理参数

0　引言　 bcl- 2基因是一种抑制凋亡基因 [1 ] ,通过基因突变或易位 ,使表达增强 .近期研究发现 Bcl- 2蛋白在非淋巴造血系统肿瘤中 ,也有异常表达 .如 :乳腺癌、前列腺癌、肺癌、鼻咽癌、胃癌、神经胶质瘤等 [2 ] ,且认为 Bcl- 2蛋白表达与预后因素有关 [3,4] .目前 ,国内有关实体瘤中 Bcl- 2表达、调节及功能与预后关系研究报道较少 .我们主要观察 Bcl- 2蛋白在乳腺癌中的表达及预后因素间的相关性 .1　材料和方法1 .1　材料　收集我院 1 995 / 1 998原发乳腺癌手术切除标本6 9例 ,均为女性 ,年龄 2 9～ 72岁 ,平均 45岁 .术前未做过任…     

Inhibition of mineralocorticoid receptors with eplerenone alleviates short-term cyclosporin A nephrotoxicity in conscious rats

BACKGROUND: Recent data indicate that aldosterone aggravates cyclosporin A (CsA)-induced nephrotoxicity. We examined whether the mineralocorticoid receptor (MR) blocker eplerenone (EPL) antagonized early deterioration of renal function and blood pressure (BP) increase in CsA-treated rats. METHODS: Male Sprague-Dawley rats received CsA (15 mg/kg/day i.p.) and/or EPL (100 mg/kg/day p.o.) for 21 days. After 2 weeks, arterial, venous and urinary bladder catheters were implanted and the rats were trained to accept a restraining device allowing arterial blood sampling and direct measurement of BP and renal function. BP was measured on-line in conscious rats. RESULTS: CsA significantly increased systolic BP: 139 +/- 4 versus 134 +/- 2 mmHg, reduced body weight gain: -5 +/- 6 versus 36 +/- 7 g, glomerular filtration rate (GFR): 1.02 +/- 0.16 versus 2.64 +/- 0.27 ml/min, renal blood flow (RBF): 5.3 +/- 2.4 versus 13.5 +/- 2.1 ml/min and lithium clearance (C(Li+)): 0.16 +/- 0.04 versus 0.26 +/- 0.07 ml/min compared to controls. These changes were prevented by simultaneous EPL treatment: systolic BP, 130 +/- 4 mmHg; weight gain, 53 +/- 7 g; GFR, 1.67 +/- 0.26 ml/min; RBF, 12.3 +/- 2.1 ml/min and C(Li+), 0.27 +/- 0.03 ml/min. Analysis of kidney morphology after the CsA treatment showed hyaline vacuolization in tubules and vascular depositions in arterioles; these changes were less pronounced after combination therapy. No significant changes were seen regarding haemoglobin, haematocrit, plasma renin and vasopressin, plasma and urinary sodium, potassium, or osmolality. CONCLUSIONS: MR blockade by EPL prevented short-term alterations in GFR, RBF and hypertension associated with CsA nephrotoxicity. We conclude that the aldosterone-MR pathway contributes markedly to the renal toxicity induced by this calcineurin inhibitor.     

A comparison of the clinical anesthetic efficacy of 4% articaine and 0.5% bupivacaine (both with 1:200,000 epinephrine) for lower third molar removal

OBJECTIVE: This study compared the clinical efficacy of 4% articaine (A200) and 0.5% bupivacaine (B200), both with 1:200,000 epinephrine, for lower third molar removal. STUDY DESIGN: Fifty patients underwent removal of symmetrically positioned lower third molars, in 2 separate appointments, under local anesthesia either with A200 or B200, in a double-blind, randomized, and crossover manner. Time to onset, duration of postoperative analgesia, duration of anesthetic action on soft tissues, intraoperative bleeding, and hemodynamic parameters were evaluated. RESULTS: A statistically significant difference between the time to onset of A200 (1.66 +/- 0.13 minutes) and B200 (2.51 +/- 0.21 minutes) was found (P < .05). There was no statistically significant difference in the duration of analgesia, whether the patient was subjected to osteotomy or not, regardless of the local anesthetic used (3 to 4 hours; P > .05). However, when patients received B200 they experienced a statistically significant longer period of anesthesia on the soft tissues as compared with when they had received A200 (around 5 hours and 4 hours, respectively, P < .05). The surgeon's rating of intraoperative bleeding was considered very close to minimal for both anesthetics. In the surgeries with osteotomy, the comparison between A200 and B200 showed statistically significant differences in the diastolic (64 mm Hg and 68 mm Hg, respectively, P = .001) and mean arterial pressure (86 mm Hg and 89 mm Hg, respectively, P = .031) when data from all the surgical phases were pooled. Additionally, the mouth opening at the suture removal was statistically different for A200 and B200 solutions (91.90% +/- 3.00% and 88.57% +/- 2.38% of the preoperative measure, respectively) when surgeries required bone removal (P < .05). CONCLUSIONS: In comparison with 0.5% bupivacaine, 4% articaine (both with 1:200,000 epinephrine) provided a shorter time to onset and comparable hemostasis and postoperative pain control with a shorter duration of soft tissue anesthesia in lower third molar removal.