多黏菌素异质性耐药的研究进展及临床意义

由于抗菌药物的大量使用,细菌的耐药性不断产生。如今,多黏菌素已成为抗多重耐药菌,尤其是碳青霉烯类耐药革兰阴性菌感染的最后一道防线药物。然而近几年来关于多黏菌素耐药的报道不断增加,并且已有研究发现多黏菌素的异质性耐药现象。异质性耐药是细菌由敏感到耐药的中间过程,常规的临床检验无法有效检测出异质性耐药,这对临床治疗用药造成了巨大的威胁,造成患者的反复感染和用药失败。但对其机制的研究较少,目前发现的主要与染色体上脂多糖(LPS)相关基因的突变,耐药基因的不稳定扩增和外排泵系统有关。本文总结了细菌异质性耐药,尤其是多黏菌素异质性耐药的研究及其临床意义。     

hs-CRP基因及rs1205基因多态性与脑梗死的相关性研究

目的分析并评价超敏C-反应蛋白(hs-CRP)基因及rs1205基因多态性与脑梗死的相关性。方法将我院神经内科急诊室2012年1月~2013年8月收治的113例中老年脑梗死患者作为观察组,以同期113例健康体检者作为对照组;通过免疫透射比浊法测定血清hs-CRP含量;以聚合酶链式反应(PCR)及限制性片段长度多态(RFLP)方法测定rs1205基因的多态性;采用美国国立卫生院神经功能缺损评分(NIHSS)量表评定神经功能。结果观察组与对照组的基因型频率与等位基因的分布趋势一致,差异不显著(P>0.05);重度患者的hs-CRP含量显著高于轻、中度两组(P<0.05);rs1205基因型与脑梗死病情程度未见相关性(P>0.05)。结论 hs-CRP含量与脑梗死患者病情密切相关,rs1205基因多态性与脑梗死发病之间未见相关性。     

MRI features of breast lymphoma: preliminary experience in seven cases

PURPOSE

We aimed to evaluate the imaging features of breast lymphoma using magnetic resonance imaging (MRI).

METHODS

This retrospective study consisted of seven patients with pathologically confirmed breast lymphoma. The breast lymphomas were primary in six patients and secondary in one patient. All patients underwent preoperative dynamic contrast-enhanced MRI and one underwent additional diffusion-weighted imaging (DWI) with a b value of 600 s/mm². Morphologic characteristics, enhancement features, and apparent diffusion coefficient (ADC) values were reviewed.

RESULTS

On MRI, three patients presented with a single mass, one with two masses, two with multiple masses, and one with a single mass and a contralateral focal enhancement. The MRI features of the eight biopsied masses in seven patients were analyzed. On MRI, the margins were irregular in six masses (75%) and spiculated in two (25%). Seven masses (87.5%) displayed homogeneous internal enhancement, while one (12.5%) showed rim enhancement. Seven masses (87.5%) showed a washout pattern and one (12.5%) showed a plateau pattern. The penetrating vessel sign was found in two masses (25%). One patient with two masses underwent DWI. Both masses showed hyperintense signal on DWI with ADC values of 0.867×10⁻³ mm²/s and 0.732×10⁻³ mm²/s, respectively.

CONCLUSION

Breast lymphoma commonly presents as a homogeneously enhancing mass with irregular margins and displays a washout curve pattern on dynamic MRI. A low ADC value may also indicate a possible diagnosis of breast lymphoma.Breast lymphoma, which constitutes only 0.04%–0.5% of all breast malignancies (1), can be divided into primary or secondary breast lymphoma (2). The majority of breast lymphomas are diffuse large B-cell lymphoma (3). The spontaneous regression of a breast lymphoma is rare and the five-year overall survival rate is 53% (1, 4). Early-stage identification and the use of radiotherapy are favorable prognostic factors, while mastectomy is associated with a poorer survival (1, 5). Therefore, a preoperative diagnosis of breast lymphoma would mean an earlier diagnosis and likely avoid unnecessary aggressive procedures.Previous studies demonstrated mammographic and ultrasonographic findings of breast lymphoma (6–8). Most lesions were high-density masses without spiculated margins and calcifications on mammography and noncircumscribed hypoechoic masses on ultrasonography (6–8). However, none were pathognomonic.Data on the magnetic resonance imaging (MRI) of breast lymphoma are limited to some single case reports (4, 7, 9–19) and small sample size case series (8, 20–23). The morphology and time-signal intensity curve (TIC) of breast lymphoma on MRI are variable. Diffusion-weighted imaging (DWI) is a functional imaging technique that is useful for distinguishing lymphoma from other malignant tumors in other systems (24, 25). However, to the best of our knowledge, the value of DWI in differentiating breast lymphoma from other malignant breast lesions has not been discussed. Therefore, the purpose of this study is to assess the MRI and DWI features of breast lymphoma.     

老年糖尿病并消化性溃疡的临床特点

目的探讨老年糖尿病患者并消化性溃疡的临床特点。方法将237例老年消化性溃疡患者按是否患糖尿病分为观察组和对照组,比较两组的临床表现、溃疡部位、溃疡直径及HP感染情况。结果两组患者在临床症状、溃疡部位、溃疡直径及HP感染率等方面比较差异均有统计学意义(P<0.05)。结论与老年单纯性溃疡患者比较,老年糖尿病并消化性溃疡患者其腹痛和反酸、暖气等症状不明显,胃溃疡和复合溃疡发生率较高,溃疡直径较大,HP感染率较高。     

腰椎附件结构性骨块植骨内固定治疗腰椎滑脱症疗效观察

目的探讨腰椎自体附件结构性植骨治疗腰椎滑脱症的有效性及可行性。方法 102例腰椎滑脱症患者,术中后路椎管减压切除腰椎棘突、椎板及关节突等附件骨,并将其回植椎间隙,作椎弓根螺钉内固定。术后随访1~10年(平均6.5年),随访患者症状缓解程度、椎间植骨融合情况、JOA评分、VAS评分、并发症,并作患者满意度调查。结果 102例患者症状均有缓解。术后、术后1年及最终随访时临床恢复率分别为80.30%、85.80%和85.10%。在术后3、6、12月患者融合率分别为26.5%、81.2%、97.9%。患者满意率达97.9%。结论腰椎附件结构性植骨生物融合能力及支撑能力可以满足临床需要,腰椎附件结构性植骨内固定治疗腰椎滑脱症可以取得满意疗效。     

Can Cytoprotective Cobalt Protoporphyrin Protect Skeletal Muscle and Muscle-derived Stem Cells From Ischemic Injury?

Background

Extremity trauma is the most common injury seen in combat hospitals as well as in civilian trauma centers. Major skeletal muscle injuries that are complicated by ischemia often result in substantial muscle loss, residual disability, or even amputation, yet few treatment options are available. A therapy that would increase skeletal muscle tolerance to hypoxic damage could reduce acute myocyte loss and enhance preservation of muscle mass in these situations.

Questions/purposes

In these experiments, we investigated (1) whether cobalt protoporphyrin (CoPP), a pharmacologic inducer of cytoprotective heme oxygenase-1 (HO-1), would upregulate HO-1 expression and activity in skeletal muscle, tested in muscle-derived stem cells (MDSCs); and (2) whether CoPP exposure would protect MDSCs from cell death during in vitro hypoxia/reoxygenation. Then, using an in vivo mouse model of hindlimb ischemia/reperfusion injury, we examined (3) whether CoPP pharmacotherapy would reduce skeletal muscle damage when delivered after injury; and (4) whether it would alter the host inflammatory response to injury.

Methods

MDSCs were exposed in vitro to a single dose of 25 μΜ CoPP and harvested over 24 to 96 hours, assessing HO-1 protein expression by Western blot densitometry and HO-1 enzyme activity by cGMP levels. To generate hypoxia/reoxygenation stress, MDSCs were treated in vitro with phosphate-buffered saline (vehicle), CoPP, or CoPP plus an HO-1 inhibitor, tin protoporphyrin (SnPP), and then subjected to 5 hours of hypoxia (< 0.5% O₂) followed by 24 hours of reoxygenation and evaluated for apoptosis. In vivo, hindlimb ischemia/reperfusion injury was produced in mice by unilateral 2-hour tourniquet application followed by 24 hours of reperfusion. In three postinjury treatment groups (n = 7 mice/group), CoPP was administered intraperitoneally during ischemia, at the onset of reperfusion, or 1 hour later. Two control groups of mice with the same injury received phosphate-buffered saline (vehicle) or the HO-1 inhibitor, SnPP. Myocyte damage in the gastrocnemius and tibialis anterior muscles was determined by uptake of intraperitoneally delivered Evans blue dye (EBD), quantified by image analysis. On serial sections, inflammation was gauged by the mean myeloperoxidase staining intensity per unit area over the entirety of each muscle.

Results

In MDSCs, a single exposure to CoPP increased HO-1 protein expression and enzyme activity, both of which were sustained for 96 hours. CoPP treatment of MDSCs reduced apoptotic cell populations by 55% after in vitro hypoxia/reoxygenation injury (from a mean of 57.3% apoptotic cells in vehicle-treated controls to 25.7% in CoPP-treated cells, mean difference 31.6%; confidence interval [CI], 28.1–35.0; p < 0.001). In the hindlimb ischemia/reperfusion model, CoPP delivered during ischemia produced a 38% reduction in myocyte damage in the gastrocnemius muscle (from 86.4% ± 7% EBD⁺ myofibers in vehicle-treated, injured controls to 53.2% EBD⁺ in CoPP-treated muscle, mean difference 33.2%; 95% CI, 18.3, 48.4; p < 0.001). A 30% reduction in injury to the gastrocnemius was seen with drug delivery at the onset of reperfusion (to 60.6% ± 13% EBD⁺ with CoPP treatment, mean difference 25.8%; CI, 12.2–39.4; p < 0.001). In the tibialis anterior, however, myocyte damage was decreased only when CoPP was given at the onset of reperfusion, resulting in a 27% reduction in injury (from 78.8% ± 8% EBD⁺ myofibers in injured controls to 58.3% ± 14% with CoPP treatment, mean difference 20.5%; CI, 6.1–35.0; p = 0.004). Delaying CoPP delivery until 1 hour after tourniquet release obviated the protective effect in both muscles. Mean MPO staining intensity per unit area, indicating the host inflammatory response, decreased by 27–34% across both the gastrocnemius and tibialis anterior muscles when CoPP was given either during ischemia or at the time of reperfusion. Delaying drug delivery until 1 hour after the start of reperfusion abrogated this antiinflammatory effect.

Conclusions

CoPP can decrease skeletal muscle damage when given early in the course of ischemia/reperfusion injury and also provide protection for regenerative stem cell populations.

Clinical Relevance

Pharmacotherapy with HO-1 inducers, delivered in the field, on hospital arrival, or during trauma surgery, may improve preservation of muscle mass and muscle-inherent stem cells after severe ischemic limb injury.

Electronic supplementary material

The online version of this article (doi:10.1007/s11999-015-4332-8) contains supplementary material, which is available to authorized users.