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Tympanotomy and sealing of the round window for treatment of sudden deafness. 鼓室开窗封闭治疗突发性耳聋。
Pub Date : 2011-05-01
Jamshaid Ul-Mulk, Søren Friis, Christoffer Holst Hahn

Introduction: The objective of this study was to evaluate the effectiveness of explorative tympanotomy and sealing of the round window in patients diagnosed with sudden deafness.

Material and methods: A retrospective study of 22 patients presenting with sudden deafness who were treated with exploratory tympanotomy and sealing of the round window. The patients initially received conservative therapy for one month. If conservative treatment had no effect, exploratory tympanotomy and sealing of the round window was performed.

Results: The median pure tone average was 67 dB before surgery. Post-operatively, it was reduced to 55 dB. This is equivalent to a 12 dB (p = 0.008) improvement. Five patients improved beyond 30 dB and three patients out of 22 fulfilled the Belfast criteria for binaural hearing at the end of the observation period. Furthermore, three months after surgery, the incidence of vertigo and tinnitus had decreased from 58% to 8% and from 50% to 17%, respectively (p < 0.001 and p = 0.04). None of the patients experienced any severe or life-threatening complications.

Conclusion: The results suggest that explorative tympanotomy and sealing of the round window may improve hearing and reduce tinnitus and vertigo after spontaneous remission has come to an end. However, randomized controlled studies are needed.

摘要:本研究的目的是评价突发性耳聋患者探索性鼓室切开术和圆窗封闭术的有效性。材料与方法:回顾性分析22例突发性耳聋患者行探索性鼓室切开术和圆窗封闭术的临床资料。患者最初接受保守治疗一个月。若保守治疗无效,则行探索性鼓室切开术并封闭圆窗。结果:术前中位纯音平均值为67 dB。术后降至55 dB。这相当于提高了12 dB (p = 0.008)。观察结束时,5例患者的听力改善到30分贝以上,22例患者中有3例达到贝尔法斯特双耳听力标准。此外,术后3个月眩晕和耳鸣的发生率分别从58%下降到8%和50%下降到17% (p < 0.001和p = 0.04)。所有患者均未出现严重或危及生命的并发症。结论:探索性鼓室切开术和封闭圆窗可以改善听力,减少自发性缓解后的耳鸣和眩晕。然而,需要随机对照研究。
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引用次数: 0
Physicians' evaluation of clinical pharmacy revealed increased focus on quality improvement and cost savings. 医生对临床药学的评价显示,他们越来越注重提高质量和节约成本。
Pub Date : 2011-05-01
Lene Juel Kjeldsen, Trine Bjerregaard Jensen, Jens Jørn Jensen

Introduction: The aims of the present study were to evaluate physicians' satisfaction with medication services delivered by a clinical pharmacist (CP); to investigate and document to which extent a CP could improve the medication quality and reduce medication costs at an intensive care unit (ICU); and to explore which types of tasks the CP was asked to perform.

Material and methods: The project was conducted at an ICU from 1 February to 31 August 2008. The intervention consisted of certain tasks being performed by a CP. The intervention was evaluated on the basis of documentation of the intervention performed and on a questionnaire filled in by physicians at the end of the study.

Results: The majority of the physicians reported that the CP's intervention had raised their attention to medication costs (70%) and medication quality (76%). This physician-reported impression correlated with the CP's intervention which improved medication quality and catalysed an annual estimated cost saving of at least DKK 330,000, which was achieved by targeting particular medication areas. The CP was asked to perform various medication-related tasks during the project period. Indeed, the physicians reported that they found the CP qualified to perform several medication-related tasks--and many physicians reported that they had benefitted from input regarding those tasks.

Conclusion: The intervention occasioned positive physician feedback on clinical pharmacy services and the study shows that the CP was perceived by the physicians as a valuable professional collaborator.

前言:本研究的目的是评估医师对临床药师(CP)提供的用药服务的满意度;调查和记录CP在多大程度上可以提高重症监护病房(ICU)的用药质量和降低用药成本;并探索CP被要求执行哪些类型的任务。材料和方法:该项目于2008年2月1日至8月31日在ICU进行。干预包括由CP执行的某些任务。干预是根据所执行的干预文件和研究结束时医生填写的问卷进行评估的。结果:大多数医生报告CP的干预提高了他们对用药费用(70%)和用药质量(76%)的关注。这种医生报告的印象与CP的干预相关,CP的干预提高了用药质量,并通过针对特定的用药区域,每年估计节省了至少33万丹麦克朗。在项目期间,CP被要求执行各种与药物相关的任务。事实上,医生报告说,他们发现CP有资格执行一些与药物相关的任务——许多医生报告说,他们从这些任务的输入中受益。结论:干预引起了医生对临床药学服务的积极反馈,研究表明,医生认为CP是一个有价值的专业合作者。
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引用次数: 0
Evaluation of the superselective radioligand [123I]PE2I for imaging of the dopamine transporter in SPECT. 超选择性放射配体[123I]PE2I对多巴胺转运体SPECT成像的评价。
Pub Date : 2011-05-01
Morten Ziebell

Imaging of the dopamine transporter (DAT) with Single Photon Emission Computer Tomography (SPECT) has increasingly been used as a biomarker for the integrity of presynaptic dopaminergic nerve cells in patients with movement disorders. 123-I-labelled N-(3-iodoprop-2E-enyl)-2-β-carbomethoxy-3β-(4-methylphenyl) nortropane, named PE2I, is a relatively new radioligand that has about 10-fold higher in vitro selectivity for the DAT than for the serotonin transporter (SERT) compared to the slightly older but very used and licensed radioligand [123I]FP-CIT (DaTSCAN). Further [123I]PE2I has faster kinetics than [123I]FP-CIT. Because of its fast kinetic properties, quantification of [123I]PE2I binding to DAT is possible using kinetic or graphical analysis following bolus injection of tracer or as a combination of bolus and constant infusion. Based on preliminary bolus trials we have been able to calculate a B/I ratio of [123I]PE2I. This B/I ratio (2.7h) gave rise to steady state conditions and excellent reproducibility. Further, manual delineation of ROI directly on SPECT images performed equally well to a MRI-defined probability map based ROI delineation in terms of intrasubject variability of binding potential of DAT. Finally the in vivo SERT binding in DAT images obtained with [123I]FP-CIT was significant as compared to the [123I]PE2I image. [123I]PE2I is a super selective SPECT DAT radioligand with optimal kinetic properties for accurate quantification of the DAT availability in striatum. Apart from the more laborious B/I design it is currently to be considered the best radioligand for imaging the DAT in the human brain with SPECT.

使用单光子发射计算机断层扫描(SPECT)成像多巴胺转运体(DAT)已越来越多地被用作运动障碍患者突触前多巴胺能神经细胞完整性的生物标志物。123- i标记的N-(3-碘丙烯基)-2-β-碳甲氧基-3 -β-(4-甲基苯基)nortropane,被命名为PE2I,是一种相对较新的放射配体,与稍老但非常使用和许可的放射配体[123I]FP-CIT (DaTSCAN)相比,它对DAT的体外选择性比血清素转运体(SERT)高约10倍。与[123I]FP-CIT相比,[123I]PE2I具有更快的动力学。由于[123I]PE2I具有快速的动力学特性,因此可以在批量注射示踪剂或批量和持续注射相结合后使用动力学或图形分析来量化[123I]PE2I与DAT的结合。根据初步的丸剂试验,我们已经能够计算出[123I]PE2I的B/I比率。这种B/I比(2.7h)产生了稳态条件和良好的重现性。此外,直接在SPECT图像上手工描绘ROI与基于mri定义的概率图的ROI描绘在数据结合电位的主体内可变性方面表现同样良好。最后,与[123I]PE2I图像相比,使用[123I]FP-CIT获得的DAT图像中的体内SERT结合具有显著性。[123I]PE2I是一种超选择性SPECT数据放射配体,具有最佳的动力学特性,可准确定量纹状体中的数据可用性。除了更费力的B/I设计外,它目前被认为是用SPECT成像人脑数据的最佳放射配体。
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引用次数: 0
Strontium in the bone-implant interface. 锶在骨-种植体界面。
Pub Date : 2011-05-01
Marianne Toft Vestermark

Total hip replacement surgery is being performed on an increasingly large part of the population and at increasingly younger age. Because we live and stay physically active longer, and since hip replacement surgery has become quite successful, the treatment is being offered to progressively more patients. Unfortunately, about 17% of hip replacement surgeries currently involve revisions. Consequently, the longevity of both the primary and revision implant is an issue and warrants further investigation. Implants undergoing early instability or even subsidence correlate with an increased risk of aseptic loosening, subsequently requiring revision. Thus, the goal is early fixation by osseointegration of the implant. For revision implants, this is an even greater challenge since an allograft is often needed during surgery to obtain immediate stability of the implant. Bone grafts are rapidly resorbed. Thus, instability of the prosthesis may develop before new bone formation is well established and can mechanically secure the prosthesis. Strontium is a dual action drug; being both bone anabolic and anti-catabolic. In the form of strontiumranelate, it is used in the treatment of osteoporosis. Strontium may potentially improve the early osseointegration and fixation of implants. This dissertation consists of three studies investigating the effect of strontium at the bone-implant interface. The questions were firstly, what is the optimal delivery method for strontium to the interface, and secondly, can strontium exercise its dual action at the interface? The studies were performed in a cementless, experimental gap model in canine. The effects of strontium were evaluated by histomorphometrical analysis of the osseointegration and mechanical push-out test of implant fixation. Different stereological methods were used for the histomorphometrical analysis of each study. The methods used were reviewed critically and found valid. Study I compared a 5% strontium-substituted hydroxyapatite (HA) coating with an HA coating after 4 weeks and 12 weeks observation time. We examined whether fixation of the implant was improved by the strontium substitution. It was found that fixation of the implant was not improved by the strontium substituted HA coating at any of the two time points. Study II compared a 5% strontium-doped HA bone graft extender with an HA bone graft extender. The bone graft extender was mixed with allograft and impacted around a titanium implant. The objective of this study was to determine whether strontium doping of the bone graft extender could protect the allograft from fast resorption and increase gap healing, leading to the improved fixation of the implant. We found that the strontium doping increased gap healing and protected the allograft, however, results of the mechanical test were inconclusive. The reason might have been that the increased gap healing had not yet reached the implant during the 4 weeks observation time, so ongrowth onto

全髋关节置换术在越来越多的人群和越来越年轻的人群中进行。因为我们的寿命和身体活动时间更长,而且由于髋关节置换手术非常成功,越来越多的患者接受了这种治疗。不幸的是,目前约17%的髋关节置换手术需要进行手术修复。因此,初级种植体和翻修种植体的寿命都是一个问题,值得进一步研究。植入物早期不稳定甚至下沉与无菌性松动风险增加相关,随后需要翻修。因此,目标是通过种植体的骨整合进行早期固定。对于翻修种植体来说,这是一个更大的挑战,因为在手术中经常需要同种异体移植物来获得种植体的立即稳定性。骨移植物被迅速吸收。因此,假体的不稳定性可能在新骨形成良好并能机械地固定假体之前发生。锶是一种双重作用药物;同时具有骨合成代谢和抗分解代谢作用。以锰酸锶的形式,它被用于治疗骨质疏松症。锶可能潜在地改善种植体的早期骨整合和固定。本论文由三个研究组成,探讨了锶在骨-种植体界面的作用。问题是,首先,锶到界面的最佳递送方式是什么?其次,锶能否在界面上发挥双重作用?研究是在一个无骨水泥的,实验性的犬齿间隙模型中进行的。通过骨整合的组织形态学分析和种植体固定的机械推出试验来评估锶的作用。采用不同的立体学方法对每项研究进行组织形态计量学分析。所使用的方法经过严格审查,发现是有效的。研究1将5%锶取代羟基磷灰石(HA)涂层与HA涂层进行了4周和12周的观察。我们检查了锶取代是否改善了植入物的固定。结果发现,在两个时间点上,锶取代羟基磷灰石涂层并没有改善种植体的固定。研究II比较了5%掺锶的HA骨移植扩展剂和HA骨移植扩展剂。骨移植扩展器与同种异体移植物混合,并在钛种植体周围嵌塞。本研究的目的是确定掺入锶的植骨扩展剂是否可以保护同种异体移植物免受快速吸收,增加间隙愈合,从而改善种植体的固定。我们发现锶掺杂能促进间隙愈合并保护同种异体移植物,但力学试验结果尚无定论。原因可能是在4周的观察时间内,增加的间隙愈合尚未到达种植体,因此种植体上的生长没有得到改善。研究III研究了0%、10%或50%锶替代生物活性玻璃涂层与HA涂层对磨砂钛合金种植体的影响。目的是确定生物活性玻璃涂层是否会改善植入物的固定,然后以剂量依赖的方式通过涂层的锶替代进一步改善。不幸的是,生物活性玻璃涂层失败了,大概是由于喷砂粉造成的铝污染。羟基磷灰石包被种植体在骨整合和机械固定方面的各项指标均较好。这些研究表明了进行进一步实验研究的重要性。即使是在调查已知代理是否用于新应用程序时也是如此。锶作为羟基磷灰石骨移植扩展剂的掺杂剂在界面中表现出双重作用的潜力。然而,锶在骨-种植体界面的递送方法显然需要进一步研究。
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引用次数: 0
Investigations of the endocannabinoid system in adipose tissue: effects of obesity/ weight loss and treatment options. 脂肪组织内源性大麻素系统的研究:肥胖/减肥的影响和治疗选择。
Pub Date : 2011-04-01
Marianne Faurholt Bennetzen

Obesity is a world wide epidemic; it is becoming more usual to be overweight or obese than to be normal weight. Obesity increases the risk of an extensive range of diseases such as cardiovascular disease, diabetes mellitus type 2, hypertension, depression and some types of cancer. Adipose tissue is more than a storage organ for surplus energy - it is also a setting for complex metabolic processes and adipose tissue releases substances that interact with other parts of the body to influence several systems including food intake and energy metabolism. The endocannabinoid system (ECS) is one of the signalling systems that control feeding behaviour. The ECS is implicated in many functions, such as pain, memory, addiction, inflammation, and feeding, and could be considered a stress recovery system. It also seems to integrate nutrient intake, metabolism and storage maintaining homeostatic balance. The ECS is a recently discovered system, and research indicates hyperactivity in obesity. The aim of this thesis is to elaborate on the relationships of this widespread system and its elements in adipose tissue in obesity. Study I is a 4 weeks rat intervention study to investigate whether weight independent effect of Rimonabant treatment exists. We found that food intake-tolerance development could be circumvented by cyclic administration of Rimonabant and implications of weight independent effects of treatment. Study II is a cross-sectional study to establish the expression of cannabinoid receptor 1 from various adipose tissue depots of lean and obese persons. In this study we conclude, that the subcutaneous adipose tissue express more CBR1 than the visceral depot in lean, but comparable levels in obese. Study III is a 10 weeks human intervention study to asses the effects on the ECS of 10% weight loss. We found reduction in the ECS in obesity that normalised with weight loss. Our results clearly show the presence of all the components of the ECS in human adipose tissue, and suggest that the ECS is reduced in adipose tissue in obesity. Our results do not support the hypothesis of hyperactivity of the ECS in human obesity. Possible future treatment of obesity with CBR1 antagonist could involve cyclic treatment of specific peripheral compounds.

肥胖是一种世界性的流行病;超重或肥胖比正常体重变得越来越普遍。肥胖增加了患一系列疾病的风险,如心血管疾病、2型糖尿病、高血压、抑郁症和某些类型的癌症。脂肪组织不仅仅是储存多余能量的器官,它也是复杂代谢过程的场所,脂肪组织释放的物质与身体其他部位相互作用,影响包括食物摄入和能量代谢在内的几个系统。内源性大麻素系统(ECS)是控制摄食行为的信号系统之一。ECS涉及许多功能,如疼痛、记忆、成瘾、炎症和进食,可以被认为是一个压力恢复系统。它似乎还整合了营养摄入、代谢和储存,维持体内平衡。ECS是最近发现的一个系统,研究表明肥胖会导致过度活跃。本文的目的是阐述肥胖中这种广泛存在的系统及其在脂肪组织中的成分之间的关系。研究I是一项为期4周的大鼠干预研究,旨在调查利莫那班治疗是否存在体重无关效应。我们发现食物摄入耐受性的发展可以通过利莫那班的循环给药和体重独立治疗的影响来规避。研究II是一项横断面研究,旨在建立瘦人和肥胖者各种脂肪组织库中大麻素受体1的表达。在这项研究中,我们得出结论,瘦人的皮下脂肪组织比内脏储存表达更多的CBR1,但肥胖的水平相当。研究III是一项为期10周的人为干预研究,以评估体重减轻10%对ECS的影响。我们发现,随着体重减轻,肥胖患者的ECS减少。我们的研究结果清楚地表明,人类脂肪组织中存在ECS的所有成分,并表明肥胖的脂肪组织中ECS减少。我们的结果不支持人类肥胖中ECS过度活跃的假设。未来使用CBR1拮抗剂治疗肥胖症的可能包括对特定外周化合物的循环治疗。
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引用次数: 0
Increased morbidity in patients undergoing abdominoplasty after laparoscopic gastric bypass. 腹腔镜胃旁路手术后腹部成形术患者发病率增高。
Pub Date : 2011-04-01
Line Bro Breiting, Jørgen Lock-Andersen, Steen Henrik Matzen

Introduction: 30-40% of the adult population in Denmark are overweight and 10-13% are obese. The number of bariatric operations reached 3,000 in 2009, and it is expected that a third or more of the patients need corrective plastic surgery.

Material and methods: Medical charts of all patients who had abdominoplasty performed during a 2.5-year period. We included 72 patients of whom 21 had lost weight after bariatric surgery and 51 patients had lost weight through diet and exercise or had not been overweight.

Results: The overall complication rate was 21% (43% of the post-bariatric patients and 12% of the non-post-bariatric patients, p < 0.01). When adjusted for the maximum body mass index (BMI) and BMI at the time of abdominoplasty, post-bariatric patients still had a higher complication rate than non post-bariatric patients (OR = 4.8; 95% CI: 0.92-25.04). Post-bariatric patients had a significantly higher maximum weight, weight at the time of abdominoplasty and had lost more BMI units.

Conclusion: Our data show that post-bariatric patients who have an abdominoplasty performed suffer a high complication rate which appears to be higher than that of patients who do not have bariatric surgery. We have also shown a tendency towards increased costs of abdominoplasty in post-bariatric patients due to a slightly longer operating time and more postoperative office visits.

简介:丹麦30-40%的成年人超重,10-13%的人肥胖。2009年的减肥手术达到了3000例,预计三分之一以上的患者需要进行矫正整形手术。材料与方法:收集2.5年内所有腹部成形术患者的病历。我们纳入了72例患者,其中21例在减肥手术后体重减轻,51例通过饮食和运动体重减轻或没有超重。结果:总并发症发生率为21%(减肥后患者占43%,非减肥后患者占12%,p < 0.01)。当调整最大体重指数(BMI)和腹部成形术时的BMI时,减肥后患者的并发症发生率仍高于非减肥后患者(OR = 4.8;95% ci: 0.92-25.04)。减肥后的患者在腹部成形术时的最大体重明显增加,BMI单位也减少了很多。结论:我们的数据显示,减肥后进行腹部成形术的患者的并发症发生率较高,似乎高于未进行减肥手术的患者。我们还发现,由于手术时间较长,术后就诊次数较多,减肥后患者腹部成形术的费用有增加的趋势。
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引用次数: 0
Phantom breast sensations are frequent after mastectomy. 乳房切除术后乳房幻感很常见。
Pub Date : 2011-04-01
Dorthe Marie Helbo Hansen, Henrik Kehlet, Rune Gärtner

Introduction: Phantom breast sensation (PBS) following mastectomy has been recognized for many years. PBS is a feeling that the removed breast is still there. The reported prevalence and risk factors have not been established in large well-defined patient series. The purpose of this study was to examine the prevalence of PBS following mastectomy and associated risk factors.

Material and methods: This study was part of a nationwide cross-sectional questionnaire study of women aged 18-70 years treated for primary unilateral breast cancer in Denmark between 1 January 2005 and 31 December 2006. A detailed questionnaire was mailed to respondents between January and April 2008. Only questionnaires from mastectomised women were analyzed. The main outcome measures were prevalence of PBS in mastectomized Danish women and adjusted odds ratio (OR) of PBS with respect to age, pain in the breast area, surgical technique, chemotherapy and radiotherapy.

Results: A total of 1,131 women (84%) answered the questionnaire. A total of 26% experienced PBS, viz. the proportion ranged from 18% to 35% within the six well defined treatment groups, but only young age was a risk factor for PBS (OR 1.030 per year; 95% CI 1.010-1.050; p = 0.0026).

Conclusion: The prevalence of PBS during the first 1-3 years after mastectomy is about 25% and it is related to young age.

导读:乳房切除术后的幻乳感觉(PBS)已被认可多年。PBS是一种被切除的乳房还在的感觉。报告的患病率和危险因素尚未在定义明确的大型患者系列中确定。本研究的目的是检查乳房切除术后PBS的患病率及相关危险因素。材料和方法:本研究是2005年1月1日至2006年12月31日期间在丹麦接受原发性单侧乳腺癌治疗的18-70岁女性的全国性横断面问卷调查的一部分。一份详细的调查问卷于2008年1月至4月期间邮寄给受访者。只分析了乳房切除妇女的问卷。主要结局指标为丹麦乳房切除术妇女中PBS的患病率,PBS的校正优势比(OR)与年龄、乳房疼痛、手术技术、化疗和放疗有关。结果:共有1131名女性(84%)回答了问卷。共有26%的患者经历过PBS,即在六个明确定义的治疗组中,这一比例从18%到35%不等,但只有年轻是PBS的危险因素(OR 1.030 /年;95% ci 1.010-1.050;P = 0.0026)。结论:乳腺切除术后1 ~ 3年内PBS患病率约为25%,且与年轻有关。
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引用次数: 0
Bacterial characteristics of importance for recurrent urinary tract infections caused by Escherichia coli. 大肠杆菌所致复发性尿路感染的重要细菌特征。
Pub Date : 2011-04-01
Karen Ejrnæs

Urinary tract infections (UTIs) are among the most common bacterial infectious diseases encountered in clinical practice and account for significant morbidity and high medical costs. Escherichia coli is the most predominant pathogen causing 80-90% of community-acquired UTIs and 30-50% of nosocomially-acquired UTIs. Recurrent UTIs (RUTIs) are reported in 25% of women within 6 months of an acute UTI episode and pose a major problem. The aim of the present thesis was to look for bacterial characteristics of importance for recurrence of UTI caused by E. coli. The thesis is based on three papers. The study is based on E. coli from 236 Swedish women with community-acquired symptomatic lower UTI from a large study of 1162 patients treated with one of three different dosing regimens of pivmecillinam or placebo. The women were evaluated clinically and bacteriologically at the initial visit and at two scheduled follow-up visits. According to pulsed-field gel electrophoresis (PFGE) and culture results all primary infecting E. coli (initial isolates, pretherapy) were assigned into whether the initial infection was followed by cure, persistence, reinfection or relapse during follow-up. The prevalence of virulence factor genes (VFGs), phylogenetic groups, biofilm formation, plasmids and resistance to antimicrobials among primary infecting E. coli causing persistence or relapse at the follow-up visits were compared with the prevalence of these among E. coli followed by cure or reinfection. Previous studies of RUTI using phenotypically based typing methods or less specific DNA based typing methods have concluded, that RUTIs are mainly attributable to reinfection with new strains. However, applying PFGE showed that 77% of RUTIs were caused by a relapse with the primary infecting E. coli (Paper I). This may support the recent observation that E. coli can invade and replicate within the murine bladder forming biofilm-like intracellular bacterial communities (IBCs) and establish quiescent intracellular reservoirs that may represent stable reservoirs for RUTIs. The IBC pathogenic cycle has not been studied in humans; however, recently exfoliated IBCs were detected in urine from women with acute uncomplicated cystitis supporting the presence of the IBC pathway and occurrence of an intracellular bacterial niche in some women with UTI. Based on a triplex PCR E. coli can be divided into four main phylogenetic groups (A, B1, B2 and D). Phylogenetic group B2 was the most predominant group among the primary infecting E. coli followed by group D, A and B1. The majority of the tested 29 VFGs were associated with phylogenetic group B2, whereas only a few VFGs were more broadly distributed among the phylogenetic groups (Paper III). Primary infecting E. coli causing persistence or relapse of the infection were associated with phylogenetic group B2, whereas primary infecting E. coli followed by cure or reinfection were associated with group D (Paper II). Phylogenetic group

尿路感染(uti)是临床实践中最常见的细菌感染性疾病之一,发病率高,医疗费用高。大肠杆菌是导致80-90%社区获得性尿路感染和30-50%医院获得性尿路感染的最主要病原体。据报道,25%的妇女在急性尿路感染发作后6个月内出现复发性尿路感染,这是一个重大问题。本论文的目的是寻找大肠杆菌引起的尿路感染复发的重要细菌特征。本论文以三篇论文为基础。该研究基于来自236名瑞典妇女的大肠杆菌,这些妇女患有社区获得性症状性下尿路感染,来自1162名接受哌美西林或安慰剂三种不同剂量方案之一治疗的患者的大型研究。在首次访问和两次预定的随访中,对这些妇女进行了临床和细菌学评估。根据脉冲场凝胶电泳(PFGE)和培养结果,将所有原代感染大肠杆菌(初始分离株、预处理株)分为初始感染后治愈、持续、再感染或随访期间复发。在初次感染的大肠杆菌中,毒力因子基因(vfg)、系统发育群、生物膜形成、质粒和抗微生物药物耐药性的流行率与治愈或再感染的大肠杆菌中这些基因的流行率进行了比较。以往使用基于表型的分型方法或特异性较低的基于DNA的分型方法对RUTI进行的研究得出结论,RUTI主要归因于新菌株的再感染。然而,应用PFGE显示,77%的ruti是由原发感染大肠杆菌的复发引起的(论文1)。这可能支持最近的观察,即大肠杆菌可以在小鼠膀胱内侵入和复制,形成生物膜样细胞内细菌群落(IBCs),并建立静止的细胞内宿主,这可能代表ruti的稳定宿主。IBC的致病周期尚未在人类中进行研究;然而,最近在急性无并发症膀胱炎妇女的尿液中检测到脱落的IBC,支持IBC途径的存在和一些UTI妇女细胞内细菌生态位的发生。经三联PCR检测,大肠杆菌可分为a、B1、B2和D 4个主要的系统发育类群,其中B2类群在原代感染大肠杆菌中最占优势,其次为D、a和B1类群。所检测的29个vfg中,大多数与系统发生组B2相关,而只有少数vfg在系统发生组中分布更广泛(论文III)。原发感染大肠杆菌导致感染持续或复发与系统发生组B2相关,而原发感染大肠杆菌后治愈或再感染与D组相关(论文II)。系统发生组B2与许多所测试的抗菌素的敏感性相关。而A组与对许多这些抗菌剂和耐多药菌株的耐药性有关,D组与耐多药菌株有关。系统发育类群A和D分别与携带IncH和IncI质粒相关。原发感染大肠杆菌的耐药模式或质粒谱与随访期间的结果(治愈、持续、再感染或复发)无关(论文II)。对氨苄西林、磺胺甲唑、链霉素和四环素的耐药与一些vfg (sfa/focDE、agn43bCFT073、chuA、iroN、cnf1、hlyD、ibeA、malX、usp)的较低患病率和其他vfg (afa/draBC、agn43aCFT073、iha、iutA、但这些抗菌素的耐药菌株和敏感菌株之间的VFG总分没有差异(论文III)。与那些治愈或再感染的大肠杆菌相比,初次感染导致持续或复发的大肠杆菌在体外具有更高的生物膜形成能力(论文II)。这表明生物膜可能是RUTI发展的重要决定因素,并可能支持IBCs的观察。原发感染大肠杆菌导致复发或持续存在的患者,其VFG总分、溶血率和许多VFG发生率高于治愈或再感染后的患者。与持续或复发相关的vgf包括:粘附素(sfa/focDE, papAH),生物膜相关因子(agn43),铁摄取系统(chuA, fyuA, iroN),保护因子(kpsM II, kpsMII K2),毒素(cnf1, hlyD), CFT073致病性相关岛的标记物(malX)和细菌素样因子(usp)。没有特定的vfg组合可以预测持续性或复发(论文III)。 大肠杆菌中至少有一种性状(系统发育组B2、sfa/focDE、papAH、agn43、chuA、fyuA、iroN、kpsM II、kpsM II K2、traT、cnf1、hlyD、ibeA、malX、usp和溶血性)呈阳性,与没有这些性状的原发性感染大肠杆菌接受三天治疗或不考虑这些性状的原发性感染大肠杆菌接受七天治疗相比,具有显著更高的持续或复发的发生率(论文III)。我们的结果可能支持大肠杆菌在膀胱细胞内蓄水池的假设。认识到尿路致病性大肠杆菌是一种潜在的细胞内病原体,对我们目前的尿路感染治疗方案提出了挑战,并主张开发新的抗菌药物或治疗方案/策略。没有明确的毒力谱可以预测RUTI。然而,我们发现与持续性或复发相关的vfg可能是预防和治疗UTI的潜在目标。此外,我们确定了潜在的标记物,可用于选择更差异化和最佳的治疗。未来的研究必须探索这些vfg和其他推测的和新的vfg在尿路感染持续或复发中的作用,以及它们在IBC形成中的可能作用。确定vfg的功能和机制可以促进开发新的诊断工具、方案和药物,以预防和治疗RUTI。
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引用次数: 0
The renin-angiotensin-aldosterone system and its blockade in diabetic nephropathy: main focus on the role of aldosterone. 肾素-血管紧张素-醛固酮系统及其在糖尿病肾病中的阻断:主要关注醛固酮的作用。
Pub Date : 2011-04-01
Katrine Jordan Schjoedt

Diabetic nephropathy is the most common cause of end-stage renal disease in the western world. Despite major improvements in both prevention and treatment of diabetic nephropathy, there is a continuous need to improve identification and treatment of "non-responders". In recent years, several experimental studies have shown that aldosterone plays a role in the development and progression of diabetic nephropathy, independent of angiotensin II and blood pressure levels. Blocking the renin-angiotensin-aldosterone system with an ACE-inhibitor (ACEI) and/or ambulatory blood pressure should theoretically inhibit the secretion of aldosterone. However, an increase in aldosterone during long-term treatment with ACEIs, so-called aldosterone escape or aldosterone breakthrough, has been described. In the present thesis, our studies evaluating the incidence and clinical impact (i.e. a faster rate of decline in kidney function) of aldosterone escape in type 1 diabetic patients with diabetic nephropathy, possible mechanisms of aldosterone escape, and finally the beneficial effect of blocking aldosterone on albuminuria, blood pressure and renal autoregulation is being reviewed, together with some aspects of the existing treatment recommendations.

在西方世界,糖尿病肾病是终末期肾脏疾病最常见的病因。尽管糖尿病肾病的预防和治疗都取得了重大进展,但仍然需要改进对“无反应者”的识别和治疗。近年来,一些实验研究表明醛固酮在糖尿病肾病的发生和进展中起作用,独立于血管紧张素II和血压水平。用ace抑制剂(ACEI)和/或动态血压阻断肾素-血管紧张素-醛固酮系统理论上可以抑制醛固酮的分泌。然而,在acei长期治疗期间,醛固酮增加,所谓的醛固酮逃逸或醛固酮突破,已被描述。在本论文中,我们的研究评估了1型糖尿病合并糖尿病肾病患者醛固酮逸出的发生率和临床影响(即肾功能下降速度更快),醛固酮逸出的可能机制,最后是阻断醛固酮对蛋白尿、血压和肾脏自身调节的有益作用,以及现有治疗建议的一些方面。
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引用次数: 0
Diagnosis and treatment of Helicobacter pylori infection. 幽门螺杆菌感染的诊断与治疗。
Pub Date : 2011-04-01
Peter Bytzer, Jens Frederik Dahlerup, Jens Ravn Eriksen, Dorte Ejg Jarbøl, Steffen Rosenstock, Signe Wildt

National Danish guidelines for the diagnosis and treatment of Helicobacter pylori (Hp) infection have been approved by the Danish Society for Gastroenterology. All patients with peptic ulcer disease, gastric cancer, and MALT lymphoma should be tested for Hp. We also recommend testing in first degree relatives to patients with gastric cancer, in NSAID-naive patients, who need long-term NSAID therapy, and in patients presenting with dyspepsia and no alarm symptoms. Non-endoscoped patients can be tested with a urea-breath test or a faecal antigen test. Endoscoped patients can be tested with a rapid urease test. Proton pump inhibitor therapy should be stopped at least 1 week prior to Hp testing. All infected patients should be offered Hp eradication therapy. First-line treatment is 7-day triple therapy with a proton pump inhibitor and clarithromycine in combination with metronidazole or amoxicilline. Quadruple therapy for 2 weeks with bismuthsubsalicylate, tetracycline, metronidazole and a proton pump inhibitor is recommended in case of treatment failure. Hp testing should be offered to all patients after eradication therapy but is mandatory in patients with ulcer disease, noninvasive gastric cancer or MALT lymphoma. Testing after eradication should not be done before 4 weeks after treatment has ended.

丹麦胃肠病学会批准了丹麦幽门螺杆菌(Hp)感染诊断和治疗国家指南。所有患有消化性溃疡疾病、胃癌和MALT淋巴瘤的患者都应进行Hp检测。我们还建议对胃癌患者的一级亲属、需要长期非甾体抗炎药治疗的未使用非甾体抗炎药的患者以及出现消化不良且无警示症状的患者进行检测。未进行内窥镜检查的患者可进行尿素呼吸试验或粪便抗原试验。内窥镜下的病人可以进行快速脲酶试验。质子泵抑制剂治疗应在Hp检测前至少1周停止。所有感染的病人都应该接受Hp根除治疗。一线治疗是质子泵抑制剂和克拉霉素联合甲硝唑或阿莫西林的7天三联治疗。如果治疗失败,建议使用次水杨酸铋、四环素、甲硝唑和质子泵抑制剂进行为期2周的四联治疗。Hp检测应提供给所有根除治疗后的患者,但对于溃疡疾病、非侵袭性胃癌或MALT淋巴瘤患者是强制性的。根除后的检测不应在治疗结束后4周之前进行。
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引用次数: 0
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Danish medical bulletin
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