噬菌体与抗生素的联合应用及其协同作用机制

抗生素滥用已导致全球范围内的抗生素耐药危机,人们不得不开始寻求新的策略解决这一问题。古老的噬菌体疗法因噬菌体杀菌效力强、可自我复制等优势而重新受到重视。但单独使用噬菌体可能面临一系列问题,如抗菌谱过窄,噬菌体抗性及免疫原性等。噬菌体与抗生素联合应用能够协同裂解宿主细菌,更好地控制或根除细菌感染,因此,二者联用在近年来开始成为噬菌体疗法的研究和应用热点。本文通过整理噬菌体与抗生素联合应用的研究文献及临床报道,探讨、总结噬菌体与抗生素的协同作用机制,以期进一步推动噬菌体与抗生素联合的研究与应用。     

经伤椎椎弓根植骨联合伤椎置钉治疗胸腰椎爆裂骨折

目的探讨经伤椎椎弓根植骨联合伤椎置钉治疗胸腰椎爆裂骨折的临床疗效。方法回顾性分析本院2008年3月～2010年1月经伤椎椎弓根植骨联合伤椎置钉治疗胸腰椎爆裂骨折病例资料59例,其中,男38例,女2l例;年龄19～65岁,平均37岁。收集的病例均为单节段椎体爆裂性骨折,所有病例采用后路经伤椎椎弓根植骨。经伤椎及上下椎椎弓根固定。比较术前术后椎体前缘高度、脊柱后凸角（矢状面Cobb角）、椎管内占位、神经功能ASIA分级等指标。结果术后随访12～24个月,平均随访17个月,术后均获得较好恢复,高度及外形基本恢复正常．无内固定物松动、断裂等并发症,手术前后椎体前缘高度、脊柱后凸角、椎管内占位比较差异均有统计学意义（p〈0．05）,神经功能ASIA分级亦有改善。结论经伤椎椎弓根植骨联合伤椎置钉治疗胸腰椎爆裂骨折可有效建立椎体前中柱稳定性,增强内固定系统的牢固性,是治疗胸腰椎爆裂骨折的一种有效方法。     

两种植骨方式治疗L1椎体爆裂骨折的有限元研究

目的　建立L1椎体爆裂骨折的有限元模型,分析比较经椎弓根椎体内植骨和经椎管椎体内植骨的应力分布。 方法　通过CT扫描、Mimics三维重建、ANSYS前处理等方法建立胸腰段T12~L2有限元模型,据此建立L1椎体爆裂骨折后经椎弓根椎体内植骨和经椎管椎体内植骨加椎弓根钉棒后路固定模型。并对模型在前屈、后伸、侧弯和旋转下加载350N/8Nm,观察分析应力分布情况。 结果　正常胸腰段、L1椎体爆裂骨折、经椎弓根植骨和经椎管植骨模型的等效应力峰值如下,前屈：6.89、54.10、8.03、5.92 MPa;后伸：56.70、109.00、12.50、8.61 MPa;侧弯：6.83、47.50、11.30、3.60 MPa;旋转：23.80、112.00、13.10、7.65 MPa。未植骨时应力主要集中于螺钉的尾部和连接棒,植骨后应力明显降低,并向螺钉中部分散分布。 结论　两种植骨方式的模型均重建了伤椎的强度,增加即时稳定性,但经椎管椎体内植骨更充分、更有效减小内固定应力,增加其力学安全性,从生物力学角度是一种植得推广的术式。     

Release pattern and structural integrity of lysozyme encapsulated in core–sheath structured poly(dl-lactide) ultrafine fibers prepared by emulsion electrospinning

The purpose of this study was to investigate the structural integrity, bioactivity and release patterns of lysozyme, as a model protein, encapsulated within the core-shell structured ultrafine fibers prepared by emulsion electrospinning. Electron microscopy and laser confocal scanning microscopy images demonstrated that the fibrous mats were very porous with integrally core-shell structured, bead-free, and randomly arrayed fibers. This structural property can pronouncedly alleviate the initial burst release and improve the sustainability of ultrafine fiber-based releasing devices. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and size exclusion chromatography were used to assess the primary structure of lysozyme, indicating that the ultra-sonication and electrospinning did not cause any remarkable denaturation of protein, while the core-shell structured fibers protected the structural integrity of encapsulated protein during incubation in the medium. Fourier transform infrared analyses showed that the electrospinning process had much less effect on the secondary structure of protein than ultra-sonication. The bioactivity assay indicated around 16% of specific activity loss during the emulsification procedure, and the protective effect of the shell materials on the activity of encapsulated protein. In vitro degradation showed that the protein entrapment led to more significant mass loss and higher molecular weight reduction.     

Inhibition of firing rate and changes in the firing pattern of nigral dopamine neurons by γ-hydroxybutyric acid (GHBA) are specifically induced by activation of GABAB receptors

 Previous studies have shown that administration of γ-hydroxybutyric acid (GHBA) or the GABA_B receptor agonist baclofen are associated with a decrease in firing rate, a regularisation of firing pattern and a decrease in burst activity of midbrain dopamine (DA) neurons in the substantia nigra (SN). In the present study we compared the ability of the novel GABA_B receptor antagonist SCH 50911 and the selective antagonist of GHBA binding sites, NCS-382, to antagonise the effects of baclofen or GHBA, respectively, on the neuronal activity of DA neurons in anaesthetised rats. SCH 50911 (75 mg/kg, i.v.) was found to antagonise the decrease in firing rate, the regularisation of firing rhythm and the decrease of burst activity in DA cells, induced by baclofen (1–32 mg/kg, i.v.) or GHBA (12.5–1600 mg/kg, i.v.). NCS-382 (100 mg/kg, i.v.) did not affect the baclofen-induced changes in neuronal activity. Neither was the drug able to influence the GHBA-induced alterations in firing rate or in burst activity, although NCS-382 to some extent antagonised the regularisation of the firing pattern observed following low doses of GHBA (≤100 mg/kg). The results of the present study give further support for the notion that the GHBA-induced changes in neuronal activity of nigral dopamine neurons are mediated by stimulation of GABA_B receptors. Received: 13 October 1997 / Accepted: 10 March 1998     

Spine fractures in falling accidents: analysis of multidetector CT findings

The purpose of the present study was to assess incidence, fracture type, and location of spine fractures due to falls. All emergency room CT requests during a time period of 26 months were reviewed retrospectively. Patients who had fallen or jumped and were initially examined with multidetector CT (MDCT) were included. The MDCT studies were evaluated by two radiologists for trauma location, fracture type, and multiple level involvement. A total of 237 patients (184 males, 53 female, age range 16–86 years, mean age 42 years) met the inclusion criteria. A total of 203 vertebral fractures were seen in 127 patients. Burst fracture (n=78) was the most frequent type of trauma, usually located in the thoracolumbar junction (50%). Also, compression fracture (n=52) was most common in the thoracolumbar junction (39%). Posterior column fracture (n=52) was most frequently detected in the cervical spine (40%). Multiple-level spine fractures were seen in 41 (32%) of the injured patients, of which 12 (29%) had fractures at noncontinuous levels. With increasing height the overall incidence of fractures increased, and burst fractures and multiple level spine fractures became more frequent. Age had no effect on fracture type or location. Spine fractures due to falls are common. Burst fracture is the most common fracture type and most frequently seen in the thoracolumbar junction. Multiple-level fractures were seen in 32% of the cases, of which 29% were seen at noncontinuous levels. Serious spine fractures are seen in all falling height and age groups.     

Burst strength of laparoscopic and open hernia repair

Background: There are few reports of overall strength of laparoscopic and open incisional hernia repair. Methods: After anesthesia, a 2-inch circular defect was made in the abdominal wall of 28 female swine. Gore-Tex DualMesh Biomaterial (W. L. Gore & Associates, Flagstaff, AZ) was used for all repairs. Sixteen animals underwent open repair and 12 underwent laparoscopic repair. Burst strength was detected within 2 weeks and at 6 weeks by euthanizing the animals and insufflating the abdominal cavity with water while measuring the intraabdominal pressure until it could no longer be pressurized. Results: Three events occurred after insufflation: rupture around patch (R), dissection from insufflation or pressure monitoring sites (D), or rectal prolapse (P). Failure after open early repair occurred at 289 (range 219–388) mmHg with 7-R, 1-P and late 289 (196–343) mmHg with 1-R, 6-P. Failure after laparoscopic early repair occurred at 259 (191–388) mmHg with 4-R, 1-P, 1-D and late 291 (140–330) mmHg with 2-R, 1-P, 3-D. Late groups were less likely to rupture. Conclusion: Both hernia repairs are durable at early and late periods. Tissue ingrowth adds to repair strength. We could not show that one repair was stronger than the other. Nonetheless, laparoscopic repair tended to degrade by dissection, which was our highest pressure event.     

A dynamic investigation of the burst fracture process using a combined experimental and finite element approach

Spinal burst fractures account for about 15% of spinal injuries and, because of their predominance in the younger population, there are large associated social and healthcare costs. Although several experimental studies have investigated the burst fracture process, little work has been undertaken using computational methods. The aim of this study was to develop a finite element model of the fracture process and, in combination with experimental data, gain a better understanding of the fracture event and mechanism of injury. Experimental tests were undertaken to simulate the burst fracture process in a bovine spine model. After impact, each specimen was dissected and the severity of fracture assessed. Two of the specimens tested at the highest impact rate were also dynamically filmed during the impact. A finite element model, based on CT data of an experimental specimen, was constructed and appropriate high strain rate material properties assigned to each component. Dynamic validation was undertaken by comparison with high-speed video data of an experimental impact. The model was used to determine the mechanism of fracture and the postfracture impact of the bony fragment onto the spinal cord. The dissection of the experimental specimens showed burst fractures of increasing severity with increasing impact energy. The finite element model demonstrated that a high tensile strain region was generated in the posterior of the vertebral body due to the interaction of the articular processes. The region of highest strain corresponded well with the experimental specimens. A second simulation was used to analyse the fragment projection into the spinal canal following fracture. The results showed that the posterior longitudinal ligament became stretched and at higher energies the spinal cord and the dura mater were compressed by the fragment. These structures deformed to a maximum level before forcing the fragment back towards the vertebral body. The final position of the fragment did not therefore represent the maximum dynamic canal occlusion.     

Nonoperatively treated burst fractures of the thoracic and lumbar spine in adults: a 23- to 41-year follow-up

BACKGROUND CONTEXT: Several studies report a favorable short-term outcome after nonoperatively treated two-column thoracic or lumbar burst fractures in patients without neurological deficits. Few reports have described the long-term clinical and radiological outcome after these fractures, and none have, to our knowledge, specifically evaluated the long-term outcome of the discs adjacent to the fractured vertebra, often damaged at injury and possibly at an increased risk of height reduction and degeneration with subsequent chronic back pain. PURPOSE: To evaluate the long-term clinical and radiological outcome after nonoperatively treated thoracic or lumbar burst fractures in adults, with special attention to posttraumatic radiological disc height reduction. STUDY DESIGN: Case series. PATIENT SAMPLE: Sixteen men with a mean age of 31 years (range, 19-44) and 11 women with a mean age of 40 years (range, 23-61) had sustained a thoracic or lumbar burst fracture during the years 1965 to 1973. Four had sustained a burst fracture Denis type A, 18 a Denis type B, 1 a Denis type C, and 4 a Denis type E. Seven of these patients had neurological deficits at injury, all retrospectively classified as Frankel D. OUTCOME MEASURES: The clinical outcome was evaluated subjectively with Oswestry score and questions regarding work capacity and objectively with the Frankel scale. The radiological outcome was evaluated with measurements of local kyphosis over the fractured segment, ratios of anterior and posterior vertebral body heights, adjacent disc heights, pedicle widths, sagittal width of the spinal canal, and lateral and anteroposterior displacement. METHODS: From the radiographical archives of an emergency hospital, all patients with a nonoperatively treated thoracic or lumbar burst fracture during the years 1965 to 1973 were registered. The fracture type, localization, primary treatment, and outcome were evaluated from the old radiographs, referrals, and reports. Twenty-seven individuals were clinically and radiologically evaluated a mean of 27 years (range, 23-41) after the injury. RESULTS: At follow-up, 21 former patients reported no or minimal back pain or disability (Oswestry Score mean 4; range, 0-16), whereas 6 former patients (of whom 3 were classified as Frankel D at baseline) reported moderate or severe disability (Oswestry Score mean 39; range, 26-54). Six former patients were classified as Frankel D, and the rest as Frankel E. Local kyphosis had increased by a mean of 3 degrees (p<.05), whereas the discs adjacent to the fractured vertebrae remained unchanged in height during the follow-up. CONCLUSIONS: Nonoperatively treated burst fractures of the thoracic or lumbar spine in adults with or without minor neurological deficits have a predominantly favorable long-term outcome, and there seems to be no increased risk for subsequent disc height reduction in the adjacent discs.