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Biomechanical assessment of the reconstruction of the anterolateral ligament during anterior cruciate ligament surgery 前交叉韧带手术中前外侧韧带重建的生物力学评估
Pub Date : 2017-01-01 DOI: 10.4172/Clinical-Investigation.1000117
M. Komzák, R. Hart, L. Paša, P. Smid, D. Náhlík, T. Pavlík
Background: Rotational instability after the anterior cruciate ligament (ACL) injury and subsequent reconstruction may be caused by the rupture of the anterolateral structures of the knee, specifically the anterolateral ligament (ALL). There are more techniques to improve the rotational stability of the knee. The objective of this randomised cohort study was: (1) To evaluate the knee rotational stability after the single-bundle ACL reconstruction (SB) with addition of the ALL reconstruction and to compare it with the double-bundle ACL reconstruction technique (DB). (2) To analyse when the ALL is necessary to reconstruct. Methods and findings: 60 patients underwent the ACL reconstruction with the average age of 29.5 years. In thirty patient’s knees the ACL was replaced with quadriceps muscle graft using the SB technique in combination with the ALL reconstruction by the gracilis graft (ALL group). With another thirty patients the ACL was reconstructed performing DB technique with the use of hamstring tendons (DB group). The rotational stability was studied before and after the reconstruction of the ACL in time “zero” using the computer navigation system. In the ALL group, the rotational stability was also analysed after the ALL reconstruction. Before the surgery, the mean internal rotational instability (IR) was 18.7° in DB group and 19.1° in ALL groups. After the DB reconstruction, IR stability improved to 10.4°. After the ACL reconstruction in the ALL group, the IR stability was 13.3°. When the ALL was added, the IR stability improved up to 9.8°. In cases where IR stability achieved 12° after the ACL reconstruction, the addition of the ALL reconstruction would not further significantly improve the IR stability. Conclusions: The SB reconstruction of the ACL using the quadriceps muscle graft in combination with the ALL reconstruction restores the IR stability of the knee to same extent as DB reconstruction does. If the IR stability after the SB reconstruction achieves 12°, the ALL reconstruction is no longer necessary
背景:前交叉韧带(ACL)损伤和重建后的旋转不稳定可能是由膝关节前外侧结构破裂引起的,特别是前外侧韧带(ALL)。有更多的技术来提高膝盖的旋转稳定性。本随机队列研究的目的是:(1)评估单束前交叉韧带重建(SB)加ALL重建后的膝关节旋转稳定性,并与双束前交叉韧带重建技术(DB)进行比较。(2)分析何时需要重建ALL。方法和结果:60例患者行前交叉韧带重建,平均年龄29.5岁。在30例患者的膝关节中,采用SB技术联合股薄肌移植物重建ALL (ALL组),用股四头肌移植物代替前交叉韧带。另外30例患者采用腘绳肌腱行DB技术重建前交叉韧带(DB组)。利用计算机导航系统研究了前交叉韧带重建前后在时间“零”点的旋转稳定性。ALL组还分析ALL重建后的旋转稳定性。术前DB组平均内旋不稳定性(IR)为18.7°,ALL组平均IR为19.1°。DB重建后,红外稳定性提高到10.4°。ALL组ACL重建后IR稳定性为13.3°。加入ALL后,红外稳定性提高到9.8°。在ACL重建后IR稳定性达到12°的情况下,添加ALL重建不会进一步显著改善IR稳定性。结论:采用股四头肌移植物联合ALL重建前交叉韧带的SB重建与DB重建在一定程度上恢复膝关节的IR稳定性。如果SB重建后的IR稳定性达到12°,则不再需要ALL重建
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引用次数: 0
A randomized, double-blind, controlled study to evaluate clinical efficacy and safety of novel filmogen osmotic treatment for pharyngitis 一项随机、双盲、对照研究评价新型丝状原渗透治疗咽炎的临床疗效和安全性
Pub Date : 2017-01-01 DOI: 10.4172/CLINICAL-INVESTIGATION.1000115
M. Rousse, H. Schutte, M. Guy, G. Clairefond, R. Shrivastava
Background: Pharyngitis is caused principally by primary viral infection: virus growth causes lysis of throat mucosa cells, leading to inflammation, secondary bacterial infection, accumulation of contaminants on the throat, and clinical signs of sore throat infection. Currently available drugs only provide partial therapeutic action or relief. Since pharyngitis is a multifactorial condition, a multi target treatment should be more effective. We tested a novel hypertonic, highly osmotic, filmogen liquid bandage which can mechanically clean the throat surface to quickly alleviate the symptoms while also eliminating their causing pathogens. A clinical trial was conducted to evaluate its efficacy and safety. Methods and findings: A 14-day, randomized, placebo controlled, double blind, efficacy and safety study was conducted in 36 treated with Test Product (TP) v/s 18 treated with Comparator Product (CP, containing saline solution) patients suffering from sore throat infection. Products were applied as spray, every 20 to 30 min. during the first 2-3 hours then 3-4 times daily, for a maximum 14 days, and primary and secondary sore throat infection-related parameters were evaluated on days 1, 2, 3, 4, 7, and 14. Saline solution showed some beneficial effects on sore throat, but the TP proved significantly more effective, producing not only very rapid but also durable effects on all clinical signs of pharyngitis. The statistically significant effectiveness and rapidity of results obtained with the test product, led to faster recovery and reduced need for antibiotics compared to the CP group. No treatmentrelated undesirable or adverse effect was observed. Conclusions: This novel hypertonic, highly osmotic, filmogen liquid bandage is a safe and effective treatment for pharyngitis.
背景:咽炎主要是由原发性病毒感染引起的:病毒生长导致喉咙粘膜细胞溶解,导致炎症,继发性细菌感染,喉咙上积聚污染物,临床表现为喉咙痛感染。目前可用的药物只能提供部分治疗作用或缓解。由于咽炎是一种多因素的疾病,多靶点治疗应该更有效。我们测试了一种新型的高渗、高渗透、丝状原液体绷带,它可以机械地清洁喉咙表面,迅速缓解症状,同时也消除了引起症状的病原体。临床试验评价其有效性和安全性。方法和研究结果:对36例使用试验产品(TP)治疗的咽喉痛感染患者进行了为期14天的随机、安慰剂对照、双盲、疗效和安全性研究,18例使用比较产品(CP,含生理盐水溶液)治疗的患者进行了比较。在最初的2-3小时内,每20 - 30分钟喷雾一次,然后每天3-4次,最多使用14天,并在第1、2、3、4、7和14天评估原发性和继发性喉咙痛感染相关参数。生理盐水溶液对喉咙痛有一定的疗效,但TP被证明更有效,对所有咽炎的临床症状不仅产生非常迅速而且持久的效果。与CP组相比,测试产品获得的结果具有统计学意义的有效性和快速性,导致更快的恢复和减少对抗生素的需求。未观察到与治疗相关的不良或不良反应。结论:这种新型的高渗、高渗透、丝原液体绷带是一种安全有效的治疗咽炎的方法。
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引用次数: 0
Antibacterial effect of polyphenols extracted from different honeys against methicillin-resistant staphylococcus aureus 不同蜂蜜多酚对耐甲氧西林金黄色葡萄球菌的抑菌作用
Pub Date : 2017-01-01 DOI: 10.4172/CLINICAL-INVESTIGATION.1000103
Belkhodja H, B. A., M. B.
Title: Antibacterial Effect of Polyphenols Extracted from Different Honeys against Methicillin- Resistant Staphylococcus aureus. Background: Methicillin resistant Staphylococcus aureus present multiple problems of nosocomial infectious diseases, in addition to the multidrug resistance. Our work aims to evaluate the antibacterial effect of four polyphenolic extracts from honey against Methicillin resistant Staphylococcus aureus. Methods and findings: An extraction of polyphenol was carried out from different honey samples collected from different sites of the Algerian territory. Then, the study of the antibacterial effect was performed by the determination of inhibition diameter and the minimal inhibitory concentration. The results indicated that the extracts of honey presented different total phenolic content with high value of 76 ± 1.1 mg GAE/100 g of fresh weight. It was clearly showed the sensitivity of MRSA against polyphenolic extracts. This inhibitory effect was found for the four samples tested with varying degrees of inhibition. The polyphenolic extract of Jijel has the highest inhibitory effect among all extracts with the MIC of 0.095 I¼l/ml. Conclusions: The study of the antibacterial effect of honey extracts allowed us to present an alternative way against the infectious diseases.
题目:不同蜂蜜多酚提取物对耐甲氧西林金黄色葡萄球菌的抑菌作用。背景:耐甲氧西林金黄色葡萄球菌除具有多药耐药外,还存在多种医院感染性疾病问题。本研究旨在评价四种蜂蜜多酚提取物对耐甲氧西林金黄色葡萄球菌的抑菌作用。方法和发现:从阿尔及利亚境内不同地点采集的不同蜂蜜样品中提取多酚。然后通过测定抑菌直径和最小抑菌浓度对其抑菌效果进行研究。结果表明,蜂蜜提取物的总酚含量不同,最高值为76 ±1.1 mg GAE/100 g鲜重。结果表明,MRSA对多酚提取物具有敏感性。这种抑制作用是在四个不同程度抑制的样品中发现的。其中,吉瑞尔多酚提取物的抑制作用最强,MIC为0.095 μ l/ml。结论:通过对蜂蜜提取物抗菌作用的研究,为防治传染病提供了另一种途径。
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引用次数: 0
Selection of Methods for Percutaneous Endoscopic Gastrostomy (PEG) that is more Safety and Useful Techniques on the Patients 经皮内镜胃造口术(PEG)安全实用的方法选择
Pub Date : 2017-01-01 DOI: 10.4172/CLINICAL-INVESTIGATION.1000119
K. Kawaura, T. Itoh, Kazutosi Hamada, H. Kitakata, Sadahumi Azukisawa, H. Okamura, S. Urashima, M. Sakurai, M. Ishizaki
Objective: Percutaneous endoscopic gastrostomy has been widely adopted, and its use is increasing in Japan due to the rapid aging of society and promotion of medical care at home. Percutaneous endoscopic gastrostomy is performed in patients with a variety of underlying basic diseases. Therefore, a procedure that is safe and less burdensome for the patient is required. Material and methods: We studied a percutaneous endoscopic gastrostomy procedure that is both safe and less burdensome, in 260 patients undergoing gastrostomy in our department. The items studied were postoperative risk factors for fever, postoperative risk factors for elevated leukocyte count, and risk factors for C-reactive protein (CRP) elevation. Results: Serious complications were fewer with the three-point fixing method of the abdominal and gastric walls. Multivariate analysis indicated that the conventional Pull method was an independent risk factor for fever (P<0.0001), and the bedridden state of the patient was a risk factor for leukocyte elevation. High Prognostic Nutrition Index (PNI) was an independent risk factor for CRP elevation. Conclusions: Percutaneous endoscopic gastrostomy performed with the Modified Introducer method by fixing the abdominal and gastric walls showed fewer complications and reduced burden on the patient compared to other methods.
目的:经皮内镜胃造口术已被广泛采用,在日本,由于社会的快速老龄化和家庭医疗的推广,其使用正在增加。经皮内镜胃造口术适用于多种潜在基础疾病的患者。因此,需要一种安全且对患者负担较轻的手术。材料和方法:我们对在我科接受胃造口术的260例患者进行了经皮内镜胃造口术的研究,该手术既安全又负担轻。研究项目包括术后发热危险因素、术后白细胞计数升高危险因素和c反应蛋白(CRP)升高危险因素。结果:采用腹胃壁三点固定法,严重并发症较少。多因素分析显示,常规拉法是发热的独立危险因素(P<0.0001),卧床状态是白细胞升高的危险因素。高预后营养指数(PNI)是CRP升高的独立危险因素。结论:经皮内镜胃造口术采用改良的固定化腹壁和胃壁的导入器方法,并发症少,患者负担轻。
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引用次数: 0
Glutathione S-Transferase T1 and M1 Gene Polymorphisms among Breast Cancer Susceptible Ghanaians 加纳乳腺癌易感人群谷胱甘肽s -转移酶T1和M1基因多态性
Pub Date : 2017-01-01 DOI: 10.4172/CLINICAL-INVESTIGATION.1000120
Benjamin Arko-Boham, E. Tagoe, BerniceAdjorogbe, N. Aryee, S. M. Adadey, O. Quaye, J. Clegg-Lamptey
Background: Glutathione S-transferase (GST) gene polymorphism has been associated with breast cancer; however, there are conflicting results. Little or no information exists in the Ghanaian population. Aim: To determine the association between GST polymorphic genes (GSTM1 and GSTT1) and susceptibility to breast cancer in Ghanaian population. Method: 112 whole blood samples were retrieved from -80oC freezer. Samples comprised 56 female breast cancer patients. Demographic and clinical data were retrieved from records. Patients were age matched with 56 controls. Genomic DNA was extracted; GSTTI and GSTM1 genes amplified using multiplex PCR with appropriate primers and the resultant amplicons separated by agarose gel electrophoresis. Results: The prevalence of GSTT1 null in patients was 42.9% and with greater association with breast cancer (OR=2.84, 95% CI=1.52–5.29, p=0.001). The heterozygous GSTT1 null/GSTM1 genotype was strongly associated with breast cancer (OR=3.02, 95% CI=1.61–5.66, p 0.05). However, the presence of both genes was not a risk factor of breast cancer in the patients (OR=0.53, 95% CI=0.28–1.09, p=0.030). Conclusion: The GSTT1 null and GSTT1 null / GSTM1 genotypes may be potential risk factors for breast cancer susceptibility.
背景:谷胱甘肽s -转移酶(GST)基因多态性与乳腺癌有关;然而,结果却相互矛盾。关于加纳人口的信息很少或根本没有。目的:确定GST多态性基因(GSTM1和GSTT1)与加纳人群乳腺癌易感性之间的关系。方法:从-80℃冷冻库中采集全血112份。样本包括56名女性乳腺癌患者。从记录中检索人口统计学和临床数据。患者与56名对照者年龄匹配。提取基因组DNA;GSTTI和GSTM1基因用多重PCR扩增,用合适的引物扩增,所得扩增子用琼脂糖凝胶电泳分离。结果:患者中GSTT1 null的患病率为42.9%,与乳腺癌的相关性更大(OR=2.84, 95% CI= 1.52-5.29, p=0.001)。杂合子GSTT1 null/GSTM1基因型与乳腺癌密切相关(OR=3.02, 95% CI=1.61 ~ 5.66, p 0.05)。然而,这两个基因的存在并不是患者患乳腺癌的危险因素(OR=0.53, 95% CI= 0.28-1.09, p=0.030)。结论:GSTT1缺失和GSTT1缺失/ GSTM1基因型可能是乳腺癌易感性的潜在危险因素。
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引用次数: 2
The Relation Of Oxidative Stress Biomarkers With Proinflammatory Cytokines In Gestational Diabetes 妊娠期糖尿病氧化应激生物标志物与促炎因子的关系
Pub Date : 2017-01-01 DOI: 10.4172/CLINICAL-INVESTIGATION.1000110
S. Genc, Zeynep Kusku-Kiraz, E. Dervişoğlu, N. Oztop, N. Dinccag, F. Gurdol
Background: It has been shown that the synthesis and secretion of cytokines is influenced by the imbalance in oxidant/antioxidant status. In this study, the relation between the circulating levels of oxidative stress biomarkers and proinflammatory cytokines was searched in gestational diabetes mellitus (GDM) patients in order to evaluate the possible role of oxidative stress in ongoing proinflammatory condition and impaired glucose homeostasis. Methods and findings: 33 pregnant women with GDM and 20 pregnant free of any maternal or fetal disorders were included in the study. Visfatin, TNF-α, IL-1β, IL-6, IL-10 and anti-ox-LDL levels were determined by ELISA. Malondialdehyde (MDA) levels and total antioxidant status (TOS) were measured spectrophotometrically. In the GDM group, MDA levels were significantly elevated (p=0.001), while the increment in TOS showed a borderline significance (p=0.05) as compared to the control group. Anti-ox-LDL of both groups remained unchanged. Serum IL-6 and IL-1β were significantly high (p=0.039, and p=0.04) in the GDM group, visfatin and IL-10 were similar in both groups. Slight but no significant increases in TNF-α levels were observed. TNF-α was associated with anti-ox-LDL (r=0.307, p=0.038) and HbA1c (r=0.352, p=0.05), MDA were correlated with TNF-α (r=0.420, p=0.004), TNF-α /IL-1β ratio (r=0.421, p=0.018), and with HbA1c (r=442, p=0.013). Anti-ox-LDL was correlated with TNF-α /IL-10 ratio (r=-0.361, p=0.046). Conclusion: Our results indicated that MDA and TOS levels are elevated in close association with hyperglycemia and some proinflammatory cytokines in GDM patients. According to our study, reestablishment of the oxidant/antioxidant balance should be considered as one of the main therapeutic targets in order to establish normoglycemia as well as to outweigh the inflammatory state in GDM.
背景:研究表明,细胞因子的合成和分泌受氧化/抗氧化状态失衡的影响。在这项研究中,研究了妊娠糖尿病(GDM)患者循环中氧化应激生物标志物水平与促炎细胞因子之间的关系,以评估氧化应激在持续的促炎状态和葡萄糖稳态受损中的可能作用。方法和结果:33名GDM孕妇和20名无任何母体或胎儿疾病的孕妇纳入研究。ELISA法检测血清Visfatin、TNF-α、IL-1β、IL-6、IL-10及抗ox- ldl水平。分光光度法测定丙二醛(MDA)水平和总抗氧化状态(TOS)。GDM组与对照组相比,MDA水平显著升高(p=0.001),而TOS水平的升高呈临界显著性(p=0.05)。两组抗ox- ldl水平保持不变。GDM组血清IL-6、IL-1β水平显著升高(p=0.039、p=0.04),两组血清visfatin、IL-10水平相似。观察到TNF-α水平轻微但无显著升高。TNF-α与抗ox- ldl (r=0.307, p=0.038)、HbA1c (r=0.352, p=0.05)相关,MDA与TNF-α (r=0.420, p=0.004)、TNF-α /IL-1β比值(r=0.421, p=0.018)、HbA1c (r=442, p=0.013)相关。Anti-ox-LDL与TNF-α /IL-10比值相关(r=-0.361, p=0.046)。结论:GDM患者血清MDA和TOS水平升高与高血糖及部分促炎因子密切相关。根据我们的研究,重建氧化/抗氧化平衡应被视为主要的治疗目标之一,以建立正常的血糖水平,并克服GDM的炎症状态。
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引用次数: 9
Microbiological Approach in Diagnosing Native and Heart Valves Prosthesis Infections 微生物学方法诊断心脏瓣膜和假体感染
Pub Date : 2017-01-01 DOI: 10.4172/CLINICAL-INVESTIGATION.1000112
C. Fontana, M. Favaro, P. Sordillo, C. Sarrecchia, S. Minelli, M. C. Bossa, A. Altieri, C. Favalli
Background: Traditional culturing approaches either on native (NV) or on prosthetic valves (PV) are still not efficient in detecting pathogens responsible of infection. In fact, despite the continuous development of microbiological technologies, a truly valid technique that could be used as reference has yet to be found. Here we present a revised version of traditional culture methods based on a pre-treatment of both NVs and PVs by DL–dithiothreitol (DTT). Methods and findings: A total of 79 specimens were included in the study: 54 were NVs and 25 were PVs. We compared the results of both culturing methods and molecular assays performed on NVs/PVs collected in two different periods named pre-DTT and post-DTT, respectively. The protocol consisted in treating NV/PV by an appropriate volume of DTT, following which the suspension of bacteria/DTT was used for culture and molecular assay. In pre-DTT period five specimens were culture-positive and one was positive by molecular assay only (1/20; 5%), showing a culture positivity rate of 25% (5/20). In the post-DTT period, of 59 specimens processed, 19 were culture positive (19/59; 32%). Moreover, PCRs performed on specimens treated with DTT contributed to the identification of six additional positive specimens plus an identification of poly-microbial infection lost by culture (7/59; 12%). Conclusion: Our findings show that the use of DTT can be helpful in increasing the identification of microorganisms involved in NV/PV infections. Given its simple and cost-effective use and considering the issue that this technique does not require any specific instrumentation, it could easily be introduced in any laboratories. However, since our study included a limited number of specimens, more extensive studies are needed to further confirm our results.
背景:传统的人工瓣膜(PV)或天然瓣膜(NV)培养方法仍不能有效检测引起感染的病原体。事实上,尽管微生物技术不断发展,但尚未找到一种真正有效的可作为参考的技术。在这里,我们提出了一种基于dl -二硫苏糖醇(DTT)预处理NVs和pv的传统培养方法的修订版。方法和发现:共纳入79例标本,其中NVs 54例,pv 25例。我们比较了在dtt前和dtt后两个不同时期收集的NVs/ pv的培养方法和分子分析结果。该方案包括用适当体积的DTT处理NV/PV,然后使用细菌/DTT悬浮液进行培养和分子分析。dtt前5例培养阳性,1例分子检测阳性(1/20;5%),培养阳性率为25%(5/20)。在dtt后处理的59个标本中,19个培养阳性(19/59;32%)。此外,对DTT处理的标本进行的pcr鉴定有助于鉴定另外6个阳性标本,以及鉴定培养丢失的多微生物感染(7/59;12%)。结论:我们的研究结果表明,使用DTT可以帮助增加与NV/PV感染有关的微生物的鉴定。鉴于其简单和经济有效的使用,并考虑到该技术不需要任何特定仪器的问题,它可以很容易地在任何实验室中引入。然而,由于我们的研究样本数量有限,需要更广泛的研究来进一步证实我们的结果。
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引用次数: 3
Comparison between Nugent's and Hay/Ison scoring criteria for the diagnosis of Bacterial Vaginosis in WASP prepared vaginal samples Nugent与Hay/Ison评分标准在WASP制备阴道标本中诊断细菌性阴道病的比较
Pub Date : 2017-01-01 DOI: 10.4172/CLINICAL-INVESTIGATION.1000116
F. Antonucci, Walter Mir, Ola, C. Fontana
Background: The aim of this study was to compare two different Bacterial Vaginosis diagnosis criteria, Nugent’s score system and Hay/Ison criterion, by using Gram-stained vaginal smears. Materials and findings: Gram-stained smears were prepared with 10 μl and 30 μl of 100 vaginal samples, collected in ESwab®, by the WASP® automatic system. All smears were examined at 1000X magnification and assessed using both Nugent and Hay/Ison criteria. In addition, the presence of clue cells was recorded. All the slides were assessed by two different readers and reviewed by a supervisor. Considering the 10 μl smears, Nugent’s scoring results were: 90 patients with normal vaginal flora, five with intermediate flora and five with Bacterial Vaginosis. Instead, Hay/Ison criterion results were: 83 patients had Grade I, 12 Grade II and 5 Grade III. About the 30 μl ESwab® smears, the Nugent’s scoring results were: 92 patients with normal vaginal flora, three intermediate flora and five with Bacterial Vaginosis. In contrast, the results obtained by using the Hay/Ison criterion were: 84 patients had Grade I, 12 had Grade II and 4 had Grade III. Clue cells were detected in all the Bacterial Vaginosis cases. Conclusions: The Hay/Ison criterion is a credible alternative to the Nugent’s score system for the diagnosis of Bacterial Vaginosis. Furthermore, the combination of WASP® automatic system and the Hay/Ison criterion can represent a fast and reliable workflow, especially in those laboratories where the request of vaginal culture tests is extremely high.
背景:本研究的目的是比较两种不同的细菌性阴道病的诊断标准,Nugent评分系统和Hay/Ison标准,通过革兰氏染色阴道涂片。材料和发现:取100份阴道标本,分别取10 μl和30 μl,采用WASP®自动系统制备革兰氏染色涂片。所有涂片在1000倍放大镜下检查,并使用Nugent和Hay/Ison标准进行评估。此外,还记录了线索细胞的存在。所有的幻灯片都由两位不同的阅读者进行评估,并由一位主管进行审阅。考虑10 μl涂片,Nugent评分结果为:阴道菌群正常90例,中间菌群5例,细菌性阴道病5例。相反,Hay/Ison标准的结果是:83例患者为I级,12例为II级,5例为III级。对于30 μl ESwab®涂片,Nugent评分结果为:92例阴道菌群正常,3例中间菌群,5例细菌性阴道病。相比之下,使用Hay/Ison标准获得的结果是:84例患者为I级,12例为II级,4例为III级。所有细菌性阴道病病例均检出线索细胞。结论:对于细菌性阴道病的诊断,Hay/Ison标准是一种可靠的替代Nugent评分系统。此外,WASP®自动系统和Hay/Ison标准的结合可以代表一个快速可靠的工作流程,特别是在那些对阴道培养测试要求极高的实验室。
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引用次数: 9
Amantadine and phenytoin: patent protected cases of drug repositioning 金刚烷胺与苯妥英:药物重新定位的专利保护案例
Pub Date : 2017-01-01 DOI: 10.4172/CLINICAL-INVESTIGATION.1000105
J. Hesselink
Repositioning of old drugs in new indications is a hot topic. However, there are some hurdles to take, and one is related to financial attractiveness. We will discuss two examples to solve this problem based on patents: phenytoin cream for neuropathic pain and amantadine extended release for dyskinesia and other neurological disorders, and discuss amantadine, its history of repositioning and its patents in more detail. Both molecules are respectable old compounds, phenytoin was synthesized more than a century ago, and amantadine in the 50s of last century. Amantadine was first recognized as an antiviral compound in the 60s of last century, and was approved by the FDA for flu prophylaxes in 1966. Parkinson was its first repositioning indication, triggered by a case study in 1968. Subsequently a great variety of indications were explored, from fatigue in multiple sclerosis, enuresis nocturna, ADHD, up to pathological gambling and recovery after head injury. Amantadine is currently developed as an extended release formulation for levodopa-induced dyskinesia in Parkinson’s disease (preapproval phase). It is protected by a patent from 2009, claiming a special formulation and time of intake. While its antiviral mechanism of action has been clarified, the mechanisms of action in other indications are still quite enigmatic. At the end of last century, it was stipulated that amantadine and comparable drugs with unexplained mechanisms may deserve additional studies to enfold its full therapeutic potential. Based on an analysis of the clinical perspectives for amantadine at that time it was felt necessary to developing an infrastructure for funding research on new purposes for older drugs after they lose patent protection. Nearly 2 decades later such recommendation still remains valid.
老药在新适应症中的重新定位是一个热门话题。然而,有一些障碍需要克服,其中一个与经济吸引力有关。我们将讨论两个基于专利来解决这个问题的例子:用于神经性疼痛的苯妥英乳膏和用于运动障碍等神经系统疾病的金刚烷胺延长释放,并更详细地讨论金刚烷胺及其重新定位的历史和专利。这两种分子都是值得尊敬的古老化合物,苯妥英是在一个多世纪前合成的,金刚烷胺是在上世纪50年代合成的。金刚烷胺在上世纪60年代首次被认为是一种抗病毒化合物,并于1966年被FDA批准用于流感预防。帕金森是其第一个重新定位指征,由1968年的一个案例研究引发。随后探索了多种适应症,从多发性硬化症的疲劳,遗尿症,多动症,到病理性赌博和头部损伤后的恢复。金刚烷胺目前作为一种缓释制剂开发用于治疗帕金森病左旋多巴诱导的运动障碍(预批准阶段)。它受到2009年专利的保护,声称有特殊的配方和摄入时间。虽然其抗病毒作用机制已被阐明,但其在其他适应症中的作用机制仍是一个谜。在上世纪末,人们规定金刚烷胺和机制不明的类似药物可能值得进一步研究,以充分发挥其治疗潜力。根据当时对金刚烷胺临床前景的分析,人们认为有必要建立一个基础设施,为失去专利保护的旧药物的新用途研究提供资金。近20年后,这样的建议仍然有效。
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引用次数: 3
Multi-Center Study of the 99th Percentile Value of High-Sensitivity Troponin I in A Normal Healthy Chinese Population 中国正常健康人群高敏感肌钙蛋白I第99百分位值的多中心研究
Pub Date : 2017-01-01 DOI: 10.4172/Clinical-Investigation.1000111
R. Zhong, Hao Wang, Zhihua Tao, Qingfeng Chen, Zheng Zhang, X. Pu, L. Wang, Wei Chen, Hui Yuan, Ying Cao, Xing Gao, Yijie Zheng, P. Yin
Background: The aim of this study was to establish the 99th percentile value for high sensitivity troponin I in a normal healthy Chinese population and to analyze the differences between different age groups and sex and regions. Methods and Findings: The study included 1,537 cases of normal healthy subjects who were chosen according to a strict inclusion criterion. They were recruited from different regions of China and separated in different age groups. All patients were carefully scanned for any diseases or factors that might influence cardiac troponin levels. The measurement of high-sensitivity cardiac troponin was standardized and tests were repeated several times and all results recorded. We used ARCHITECT-i2000 (Abbott Laboratories, Lake Bluff, Illinois, USA) for measurement of all high sensitivity cardiac troponins. The overall value of the 99th percentile value was 26.42 pg/ml. For the male group 99th percentile value was 29.40 pg/ml and for the female group 99th percentile value was 19.46 pg/ml. The difference in cardiac troponin 99th percentile value for the male and female normal group was statistically significant (P 65 years old had a higher level of high sensitivity cardiac troponin and the difference was statistically significant when compared with other groups. The 99th percentile value corresponded to an imprecision of less than 10%. Conclusions: We established the 99th percentile value for cardiac troponin in the Chinese population and the normal range for males and females and we evaluated the analytical performance of ARCHITECT high sensitivity troponin I assays.
背景:本研究的目的是建立中国正常健康人群高敏感肌钙蛋白I的第99百分位值,并分析不同年龄、性别和地区之间的差异。方法与结果:本研究纳入1537例正常健康受试者,入选标准严格。他们来自中国不同的地区,被分为不同的年龄组。所有患者都仔细扫描了可能影响心脏肌钙蛋白水平的疾病或因素。标准化了高灵敏度心肌肌钙蛋白的测量,重复测试多次,并记录所有结果。我们使用ARCHITECT-i2000 (Abbott Laboratories, Lake Bluff, Illinois, USA)测量所有高灵敏度心肌肌钙蛋白。第99百分位值为26.42 pg/ml。男性组第99百分位值为29.40 pg/ml,女性组第99百分位值为19.46 pg/ml。男性与女性正常组心肌肌钙蛋白第99百分位值差异有统计学意义(P 65岁高敏感心肌肌钙蛋白水平较高,与其他组比较差异有统计学意义。第99个百分位值对应的不精度小于10%。结论:我们建立了中国人群中心肌肌钙蛋白的第99百分位值和男性和女性的正常范围,我们评估了ARCHITECT高灵敏度肌钙蛋白I检测的分析性能。
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引用次数: 3
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Clinical investigation
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