A prospective study concerning the relationship between metal allergy and post-operative pain following total hip and knee arthroplasty

Purpose

A prospective study was conducted to detect whether a relationship exists between metal allergy and post-operative pain in total hip and knee arthroplasty patients. We postulated that to some extent a relationship does exist between them.

Materials and methods

Patients who had undergone total hip and knee arthroplasty surgery because of hip and knee disease were included. The exclusion criteria were patients who were treated with immunosuppressor two weeks pre-operatively, skin conditions around the patch testing site, and other uncontrollable factors. Each patient agreed to patch testing for three days before surgery. Photographic images before patch testing, two and three days after patch testing were obtained to evaluate the final incidence of metal allergy. The patch tests contained 12 metal elements; chromium, cobalt, nickel, molybdenum, titanium, aluminium, vanadium, iron, manganese, tin, zirconium, and copper. Two independent observers evaluated the images. The results were divided into a non-metal allergy group and a metal allergy group. Pre-operative and postoperative VAS score, lymphocyte transforming test, and X-rays were collected to detect the relationship between metal allergy and post-operative pain following total hip and knee arthroplasty.

Results

There were 96 patients who underwent pre-operative patch testing. The overall metal allergy rate was 51.1 % (49/96) in our study. Nickel, cobalt, manganese, and tin were the most common allergic metal elements in our study. Nine inappropriate cases were excluded, and 87 patients were finally included in our study. There were 36 metal allergy and 26 non-metal allergy patients in the THA group, while 11 metal allergy and 14 non-metal allergy patients were found in the TKA group. We found no relationship existed between metal allergy and post-surgery pain in total hip and knee arthroplasty.

Conclusion

Pain caused by metal allergy usually presents as persistent and recurrent pain. The white cell count, C-reactive protein, erythrocyte sedimentation rate and postoperative radiographs were not affected. Currently, patch testing and lymphocyte transforming tests are used for metal allergy diagnosis. We deemed that a relationship between post-surgery pain and metal allergy in total hip and knee patients may exist to some extent. Larger samples and longer follow-up time are essential for further study.     

New bone formation enhanced by ADSCs overexpressing hRunx2 during mandibular distraction osteogenesis in osteoporotic rabbits

Promoting new bone formation during distraction osteogenesis (DO) in elderly patients with osteoporosis is still a challenge. In this study, we investigated the effect of gene therapy using local Runt‐related gene 2 on new bone formation during osteoporotic mandibular DO in rabbits. First, we successfully established a mandibular osteoporotic animal model by ovariectomizing rabbits. Second, the right mandibles of the osteoporotic rabbits were distracted after corticotomy. The distraction gap of the rabbits in Group A2 and B2 were injected with Adv‐hRunx2‐GFP‐transfected adipose‐derived stromal cells (ADSCs) and Adv‐GFP‐transfected ADSCs, respectively. Rabbits in Groups C2 (ovariectomized control) and D2 (sham surgery control) were injected with physiologic saline. New‐generation bone tissue in the distraction gap was analyzed via plain radiographic examinations, micro‐computed tomography, histological examinations, and biomechanical testing at weeks 3, 6, and 9 of the consolidation period. Results of above examinations showed that no ideal new bone formation was observed in Groups B2 and C2, but obvious ideal new bone formation was observed in Group A2 and D2. The results suggested that gene therapy using rhRunx2‐modified ADSCs promoted new bone formation during osteoporotic mandibular DO and effectively compensated for the detrimental effects of systemic osteoporosis on new bone formation. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:709–720, 2014.     

腺病毒载体介导肝细胞生长因子基因对血管内皮细胞的作用

目的：研究腺病毒载体介导肝细胞生长因子（HGF）基因感染血管内皮细胞后在正常供氧、缺氧及缺氧后复氧的情况下细胞的凋亡情况。方法：将分离、培养的内皮细胞分为3组，分别给予M199（对照组）、HGF（HGF组）和HGF基因腺病毒载体（Ad-HGF组），分别在正常供氧、缺氧及缺氧后复氧3种情况下观察细胞的凋亡情况。结果：Ad-HGF组及HGF组细胞凋亡数均低于对照组（P〈0．01），Ad-HGF组与HGF组细胞凋亡数差异无显著性意义。结论：腺病毒载体介导HGF基因感染内皮细胞后能在缺氧情况下有效地阻止细胞凋亡。     

Mid to Distal Small Bowel Resection with the Preservation of the Terminal Ileum Improves Glucose Homeostasis in Diabetic Rats by Activating the Hindgut-Dependent Mechanism

Background

The aim of this study was to develop a novel surgical model to test the “hindgut hypothesis” and thereby study the role of the gut in glucose homeostasis and the mechanism of action of bariatric surgery.

Method

Sprague-Dawley rats were given a high-fat and high-sugar diet and treated with 25 mg/kg streptozotocin (STZ). The fat-sugar-fed/STZ-treated rats were randomized into mid to distal small bowel resection with the preservation of the terminal ileum (DBRPI) and sham operation (which had a formal celiotomy with bowel manipulation only) groups. Rats were observed for 12 weeks after the operation. The main outcome measures were weight, food intake, non-fasting glucose, an oral glucose tolerance test (OGTT), an insulin tolerance test (ITT), the levels of fasting and glucose-induced insulin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), serum bile acids, and lipid profile.

Result

The DBRPI and sham groups exhibited no difference in weight and food intake after surgery. When compared to the sham controls, the DBRPI group displayed an improvement in non-fasting glucose, oral glucose tolerance, and insulin tolerance at 4 and 12 weeks postresection. DBRPI elicited an increased serum insulin, PYY and GLP-1 levels at 12 weeks postoperation; furthermore, DBRPI resulted in higher serum levels of triglyceride, total bile acids, total bilirubin, and direct bilirubin levels and lower free fatty acid level at 12 weeks.

Conclusions

This study provides strong evidences for the key role of hindgut in the amelioration of diabetes after bariatric surgery. Moreover, these findings confirm that DBRPI is a simple and effective surgical model for testing the “hindgut hypothesis” and focused study of biliary enterohepatic recycling in the context of bariatric operations.     

重症急性胰腺炎相关肺损伤危险期的确立

目的 通过对重症急性胰腺炎模型小鼠肺组织含水量、Ⅱ型肺泡上皮细胞的超微结构及数目、活性氧代谢产物的动态演变研究和临床资料的分析,从基础和临床的角度综合确立重症急性胰腺炎相关肺损伤的危险期.方法 ICR清洁级小鼠雨蛙素腹腔内注射50 μg/kg,每小时1次,共7次,于雨蛙素注射结束后腹腔内注射LPS 15 mg/kg来创建重症急性胰腺炎小鼠模型,设定研究点为制模前、制模后6 h、12 h、1 d,4 d、7 d,对肺组织含水量、Ⅱ型肺泡上皮细胞的超微结构和数目以及肺组织活性氧代谢产物进行了动态研究.同时回顾性分析215例来自于浙江大学医学院附属第一医院1998年1月至2006年12月收治在消化内科、胰腺外科和ICU的重症急性胰腺炎患者伴肺损伤患者(纳入标准为PaO2<60 mmHg)肺损伤的时期.样本均数差异采用F检验,P<0.05为差异有统计学意义.结果 重症急性胰腺炎小鼠肺组织含水量以制模后1 d和4 d最严蕈,Ⅱ型肺泡上皮细胞的线粒体和板层小体损伤程度以制模后1 d,4 d最为明显,Ⅱ型肺泡上皮细胞数目下降以制模后1 d最显著,肺组织活性氧代谢产物亦以制模后1 d明显升高,较其他研究点有显著性差异.临床上重症急性胰腺炎患者出现肺损伤的时间为(3.1435±1.0199)d.结论 重症急性胰腺炎相关肺损伤的危险期在重症急性胰腺炎病程的第1天至第4天之间.     

Growth feedback as a basis for persister bistability

A small fraction of cells in many bacterial populations, called persisters, are much less sensitive to antibiotic treatment than the majority. Persisters are in a dormant metabolic state, even while remaining genetically identical to the actively growing cells. Toxin and antitoxin modules in bacteria are believed to be one possible cause of persistence. A two-gene operon, HipBA, is one of many chromosomally encoded toxin and antitoxin modules in Escherichia coli and the HipA7 allelic variant was the first validated high-persistence mutant. Here, we present a stochastic model that can generate bistability of the HipBA system, via the reciprocal coupling of free HipA to the cellular growth rate. The actively growing state and the dormant state each correspond to a stable state of this model. Fluctuations enable transitions from one to the other. This model is fully in agreement with experimental data obtained with synthetic promoter constructs.As far back as the 1940s, it was known that a small fraction of a bacterial population can survive even when exposed to prolonged antibiotic treatment (1, 2). This phenomenon is termed persistence and members of the surviving subpopulation are called persisters. It has been estimated that the frequency of persisters in normal wild-type populations is extremely small, perhaps of order (3). Although the number of persisters is tiny, they are often the main obstacle to attempts to completely eradicate infection.Remarkably, there is no apparent change in the persisters’ DNA sequence; i.e., their survival is not due to mutation (4). Already in 1944, Bigger suggested that persisters are phenotypically different, in a dormant state instead of an actively growing state (1). The dormant state is presumably better able to deal with common antibiotics, which typically target only actively growing cells. Bigger’s assumption was confirmed by a later study (3). In this study, Balaban et al. investigated the persistence of a single cell of Escherichia coli by using a microfluidic device. They showed that individual persisters do not always remain in the dormant state. Instead, they stochastically transit into an actively growing state and these newly transited cells are indistinguishable from other normally growing cells. Conversely, normal cells can transit into the persistent state. Thus, bacterial persistence at the population level is governed by a single-cell “phenotypic switch.” The precise workings of this switch have to date remained unclear.In the 1980s, Moyed and Bertrand identified the first high-persistence mutant, HipA7, having a persister frequency that is near 10⁻² (4). The discovery of HipA7 facilitated the study of bacterial persistence due to its relatively high proportion of persisters. It was found that HipA7 is formed by a two-residue substitution in the HipA protein. This protein acts as a toxin in a toxin–antitoxin (TA) module (5, 6), where the hipB gene is coexpressed with hipA and the corresponding protein binds to and neutralizes HipA toxicity. To date, HipA is one of only a few molecules that are validated tolerance factors (7).There have already been several models proposed for the Hip system and its connection to persistence. Two modeling groups have claimed that fluctuations cause the apparent coexistence of these two phenotypes, growing and dormant, even though there may or may not be any formal bistability. They were partially driven to this conclusion by their inability to find bistability in their assumed dynamics. The pioneering model of Rotem et al. (8) did not consider the dimerization of HipB and the repression by the HipB dimer of the hip promoter. In the alternate formulation of Koh and Dunlop (9), the HipA-dependent reduction of the translation rate and the growth rate is not included. Thus, both these works claim that bistable states are not necessarily the mechanism underlying persister formation. However, models with a single stable state invariably predict fast transitions between persisters and normally growing cells. For example, simulations in ref. 9 show that transitions from persisters to normally growing cells typically happen within 1 h. In contrast, a sizeable number of persisters can survive even when the antibiotic treatment is maintained for longer than 1 d. If cells stay in a persister state only for less than 1 h, and the persister becomes fragile when it transits into the normally growing state, they would not survive much longer than the other normal cells. The correct picture must include a long-time duration of the persister state.One model has indeed suggested that bistability is the key to the formation of persisters (10). This model made some assumptions now known to be inaccurate, for example that free HipA undergoes dimerization and that the binding of the HipA-HipB complex to the hip promoter is independent from the binding between the HipB dimer and the hip promoter. (Actually they compete with each other in binding to the same operator sites.) However, this model does explain an interesting observation, that often persisters are formed much more readily in stationary phase and in fact persisters seen in normal exponential phase are often just the remnant of persisters formed at a different growth stage. This pattern has been called type I persistence (3) and is the type seen in the HipA7 mutant. As we will see, this occurs due to the fact that the range of bistability can depend on the growth condition. A different issue is that this model is fully deterministic and hence cannot address stochastic effects such as transitions between the two stable states.The drawbacks of these models have motivated us to construct a more precise and comprehensive stochastic model for the HipBA system. A recent paper revealing the structure of HipA and its binding has helped guide us to correct the assumptions in the previous bistable model (11). We show that our approach can consistently account for different classes of experimental data and hence can form a framework for continuing analysis of this important survival strategy for wide classes of bacteria.