颞筋膜-帽状腱膜瓣在头颈肿瘤术后缺损修复中的应用

目的:探讨颞浅血管为蒂的颞筋膜-帽状腱膜瓣在头颈肿瘤外科术后缺损修复中的应用。方法:2003年11月~2006年11月应用带蒂颞筋膜-帽状腱膜瓣修复头颈部肿瘤术后缺损12例,修复部位包括软、硬腭、口咽癌、颊黏膜、上颌骨等,缺损大小从(4×3cm)~(6×7cm)。结果:12例带蒂颞筋膜-帽状腱膜中11例(91·67%)全部存活,1例部分坏死。无一例发生供区头皮坏死及永久性脱发。远期随诊结果:随访3个月~3年,12例均无肿瘤复发,2例张口受限。结论:带蒂颞筋膜-帽状腱膜瓣血运丰富,质地较薄,柔韧性好且手术创伤小,供区隐蔽。用于修复头颈部肿瘤术后缺损,尤其是眶底壁、颅底、腭部和口咽的效果理想。     

Non-Invasive Intravital Imaging of siRNA-Mediated Mutant Keratin Gene Repression in Skin

Purpose

Small interfering RNAs (siRNAs) specifically and potently inhibit target gene expression. Pachyonychia congenita (PC) is a skin disorder caused by mutations in genes encoding keratin (K) 6a/b, K16, and K17, resulting in faulty intermediate filaments. A siRNA targeting a single nucleotide, PC-relevant mutation inhibits K6a expression and has been evaluated in the clinic with encouraging results.

Procedures

To better understand the pathophysiology of PC, and develop a model system to study siRNA delivery and visualize efficacy in skin, wild type (WT) and mutant K6a complementary DNAs (cDNAs) were fused to either enhanced green fluorescent protein or tandem tomato fluorescent protein cDNA to allow covisualization of mutant and WT K6a expression in mouse footpad skin using a dual fluorescence in vivo confocal imaging system equipped with 488 and 532 nm lasers.

Results

Expression of mutant K6a/reporter resulted in visualization of keratin aggregates, while expression of WT K6a/reporter led to incorporation into filaments. Addition of mutant K6a-specific siRNA resulted in inhibition of mutant, but not WT, K6a/reporter expression.

Conclusions

Intravital imaging offers subcellular resolution for tracking functional activity of siRNA in real time and enables detailed analyses of therapeutic effects in individual mice to facilitate development of nucleic acid-based therapeutics for skin disorders.

     

超声血流成像在设计轴型皮瓣中的应用研究

目的 :应用超声血流成像技术协助设计轴型皮瓣。方法 :用 5.5～ 10 MHz超声探头检测多个部位的轴型皮瓣轴心血管 2 4条 ,以彩色血流成像显示确定其轴心血管的起点定位及浅出的轴线 ,然后根据检测结果确定皮瓣设计方案。结果 :所有的轴心血管均根据超声血流成像显示作体表标记 ,经手术解剖证实并皮瓣转移成功。结论 :该方法具有客观准确、无创实用等优点 ,是辅助设计皮瓣的有效方法     

Microbubble-Assisted Ultrasound for Imaging and Therapy of Melanoma Skin Cancer: A Systematic Review

Recent technological developments in ultrasound (US) imaging and ultrasound contrast agents (UCAs) have improved diagnostic confidence in echography. In the clinical management of melanoma, contrast-enhanced ultrasound (CEUS) imaging complements conventional US imaging (i.e., high-resolution US and Doppler imaging) for clinical examination and therapeutic follow-up. These developments have set into motion the combined use of ultrasound and UCAs as a new modality for drug delivery. This modality, called sonoporation, has emerged as a non-invasive, targeted and safe method for the delivery of therapeutic drugs into melanoma. This review focuses on the results and prospects of using US and UCAs as dual modalities for CEUS imaging and melanoma treatment.     

Safety,Tolerability, and Efficacy of GSK1322322 in the Treatment of Acute Bacterial Skin and Skin Structure Infections

GSK1322322 represents a new class of antibiotics that targets an essential bacterial enzyme required for protein maturation, peptide deformylase. This multicenter, randomized, phase IIa study compared the safety, tolerability, and efficacy of GSK1322322 at 1,500 mg twice daily (b.i.d.) with that of linezolid at 600 mg b.i.d. in patients suspected of having Gram-positive acute bacterial skin and skin structure infections (ABSSSIs). The primary endpoint was assessment of the safety of GSK1322322, and a key secondary endpoint was the number of subjects with a ≥20% decrease in lesion area from the baseline at 48 and 72 h after treatment initiation. GSK1322322 administration was associated with mild-to-moderate drug-related adverse events, most commonly, nausea, vomiting, diarrhea, and headache. Adverse events (86% versus 74%) and withdrawals (28% versus 11%) were more frequent in the GSK1322322-treated group. Treatment with GSK1322322 and linezolid was associated with ≥20% decreases from the baseline in the lesion area in 73% (36/49) and 92% (24/26) of the patients, respectively, at the 48-h assessment and in 96% (44/46) and 100% (25/25) of the patients, respectively, at the 72-h assessment. Reductions in exudate/pus, pain, and skin infection scores were comparable between the GSK1322322 and linezolid treatments. The clinical success rates within the intent-to-treat population and the per-protocol population that completed this study were 67 and 91%, respectively, in the GSK1322322-treated group and 89 and 100%, respectively, in the linezolid-treated group. These results will be used to guide dose selection in future studies with GSK1322322 to optimize its tolerability and efficacy in patients with ABSSSIs. (This study has been registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT01209078","term_id":"NCT01209078"}}NCT01209078 and at http://www.gsk-clinicalstudyregister.com [PDF113414].)     

The Potential Role of Sensory Testing,Skin Biopsy,and Functional Brain Imaging as Biomarkers in Chronic Pain Clinical Trials: IMMPACT Considerations

Valid and reliable biomarkers can play an important role in clinical trials as indicators of biological or pathogenic processes or as a signal of treatment response. Currently, there are no biomarkers for pain qualified by the U.S. Food and Drug Administration or the European Medicines Agency for use in clinical trials. This article summarizes an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials meeting in which 3 potential biomarkers were discussed for use in the development of analgesic treatments: 1) sensory testing, 2) skin punch biopsy, and 3) brain imaging. The empirical evidence supporting the use of these tests is described within the context of the 4 categories of biomarkers: 1) diagnostic, 2) prognostic, 3) predictive, and 4) pharmacodynamic. Although sensory testing, skin punch biopsy, and brain imaging are promising tools for pain in clinical trials, additional evidence is needed to further support and standardize these tests for use as biomarkers in pain clinical trials.

Imaging of the liver, biliary tract, and pancreas

The interaction between the various noninvasive and invasive imaging modalities used to evaluate the liver, biliary tract, and pancreas is demonstrated in this article. By understanding this interaction and correlating noninvasive studies, the clinician will avoid diagnostic redundancy and the need for invasive testing may be reduced.     

Multicenter,Randomized Study of the Efficacy and Safety of Intravenous Iclaprim in Complicated Skin and Skin Structure Infections

Iclaprim is a novel antibacterial agent that is currently in development for the treatment of complicated skin and skin structure infections (cSSSI). Iclaprim specifically and selectively inhibits bacterial dihydrofolate reductase, a critical enzyme in the bacterial folate pathway, and exhibits an extended spectrum of activity against various resistant pathogens, including methicillin (meticillin)-resistant Staphylococcus aureus (MRSA). The objective of this randomized, double-blind phase II study was to compare the efficacy and safety of iclaprim to those of vancomycin in patients with cSSSI. Patients were randomized to receive 0.8 mg iclaprim/kg of body weight, 1.6 mg/kg iclaprim, or 1 g vancomycin twice a day for 10 days. Clinical cure rates for the 0.8- and 1.6-mg/kg-iclaprim treatment groups were comparable to that for the vancomycin treatment group (26/28 patients [92.9%], 28/31 patients [90.3%], and 26/28 patients [92.9%], respectively). Iclaprim also showed high microbiological eradication rates. Iclaprim exhibited an eradication rate of 80% and 72% versus 59% observed with vancomycin for S. aureus, the pathogen most frequently isolated at baseline. Five MRSA cases were observed, four in the 0.8-mg/kg-iclaprim arm and one in the vancomycin arm, and all were both clinically and microbiologically cured. Iclaprim exhibited a safety profile similar to that of vancomycin, an established drug for the treatment of cSSSI. Results from this study indicate that iclaprim is a promising new therapy for the treatment of cSSSI, in particular those caused by S. aureus, including MRSA.Skin and skin structure infections (SSSI), such as cellulitis, abscesses, traumatic-wound infections, and surgical-site infections, are a common cause of morbidity and mortality in hospital infection units (13, 14). An SSSI is classified as “complicated” (cSSSI) if the infection has spread to deeper soft tissues, if surgical intervention is necessary, or if the patient has a comorbid condition, such as diabetes or immunodeficiency, that may limit the patient''s response to therapy (2). SSSI are caused predominantly by aerobic, gram-positive pathogens, although a wide range of other pathogens may also be involved (2). Among the most common culprits identified are Staphylococcus aureus and Streptococcus pyogenes.Methicillin-resistant S. aureus (MRSA) is becoming increasingly prevalent in nosocomial cSSSI (8), accounting for up to 57.8% of S. aureus isolates between 2005 and 2007 (24). MRSA is recognized as the most common identifiable cause of SSSI among U.S. patients presenting to emergency departments (13) and was isolated from 76% of SSSI. In Europe, the EARSS estimated that in 2006, about 25% of S. aureus isolates were methicillin resistant, with an MRSA frequency ranging from less than 2% in certain northern European countries to over 40% in the United Kingdom, Ireland, and several southern European countries (3).Guidelines from the Infectious Diseases Society of America (IDSA) state that antibiotic therapy against bacterial pathogens is essential for controlling the spread of infections (11, 23). Of all the antibiotic agents currently on the market, vancomycin is the traditional reference standard for the treatment of infections caused by MRSA (12, 15). However, recent clinical findings have called into question its efficacy in the treatment of MRSA infections. The loss of accessory gene regulator function (20) and decreased susceptibility to glycopeptide agents (18) in MRSA suggest the development of resistance toward vancomycin. In addition, MIC analysis revealed a shift toward higher MICs of vancomycin for isolates over the last 5 years (22). This, alongside the increasing number of reports of vancomycin-resistant S. aureus and vancomycin-intermediate S. aureus (VISA), underscores the urgent need for novel antibiotic agents with expanded activities against resistant strains (1, 2, 5). Among the antibacterial agents currently on the market are linezolid, daptomycin, and tigecycline. Although these agents are also active against gram-positive bacteria, including MRSA, there are increasing reports of resistance and patient tolerance issues with these agents (12, 17, 21). Thus, there is the need not only for new antibacterial agents but also for agents with distinct mechanisms of action.Iclaprim belongs to the class of selective dihydrofolate reductase (DHFR) inhibitors, whose safety and efficacy has been clinically proven for over 4 decades (6). Trimethoprim (TMP) is a well-established member of this class and has been successfully employed both as a monotherapy and in combination with other agents (such as sulfamethoxazole) (6, 16). However, despite the good overall safety and efficacy profile of TMP, it is only weakly bactericidal, and resistance has emerged due to the presence of specific mutations in bacterial DHFR (16).Iclaprim is the result of a rational drug optimization program and is a potent and selective DHFR inhibitor (6, 16). Iclaprim is able to inhibit bacterial DHFRs with little or no inhibition of the human enzyme at concentrations 4 orders of magnitude higher than needed for bacterial DHFR inhibition (6, 16). In addition, iclaprim in vitro is rapidly bactericidal to many pathogens at concentrations close to its MIC, achieving 99.9% reductions in bacterial loads of pathogens (such as MRSA and VISA) within 6 h, and demonstrates a postantibiotic effect lasting up to several hours (4, 7). Microbiological studies of a wide variety of pathogens from the United States and Europe have demonstrated that iclaprim has an extended spectrum of activity and is more potent than TMP against major gram-positive pathogens, particularly S. aureus and other streptococci, including strains resistant to TMP, methicillin and oxacillin, macrolides, quinolones, and glycopeptides, including VISA and vancomycin-resistant S. aureus (5, 16, 19).This is the first report describing the clinical efficacy and safety of intravenous (i.v.) iclaprim in comparison to those of vancomycin for the treatment of patients with cSSSI.(This work was presented in part at the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy [9].)     

Imaging of the glossopharyngeal, vagus, and accessory nerves

The origination and course of the glossopharyngeal, vagus and accessory cranial nerves explains their function and localizes pathology. Abnormalities of these lower cranial nerves may be intrinsic or extrinsic and is due to a multiplicity of disease processes. The clinical presentation of the involved cranial nerve helps to guide imaging evaluation. Magnetic resonance imaging without and with contrast is the mainstay of imaging of cranial nerves IX, X and XI pathology, but computed tomography provides substantial information as well.     

组织速度、应变率与应变成像诊断冠心病的临床对比研究

目的比较组织速度成像（TVI）、应变率成像（SRI）与应变成像（SI）检测冠心病心肌缺血的临床应用价值。 方法应用TVI、SRI和SI测定55例冠心病患者与42例正常人左室前间隔与后壁径向、各室壁节段纵向收缩期及快速充盈期的峰值速度（V，包括Vs和Ve））、应变率（SR，包括SRs和SRe）和应变（ε，包括εS和εE）参数，以冠脉造影结果为标准，比较该3项技术诊断心肌缺血的灵敏度（Se）和特异度（Sp）。 结果径向SRS SRE诊断心肌缺血的Sp显著高于VS与VE[（0．83±0．06 vs 0.71±0．05）cm／s，（0．80±0．10 vs 0．73士0．07）cm／s；P＜0．05]。纵向SRs和εs的Se及Sp显著高于Vs（Se：0．83±0．06和0、77±0.07 vs 0．71±0．07；P＜0．01；Sp：0．80±0．07和0．74±0．07 vs 0．68±0.08；P分别小于0．01和0．05）。纵向SRs的Se与Sp均明显高于εs（P分别小于0．01和0．05）。 结论SRI与SI诊断冠心病心肌缺血优于TVI，而SRI检测缺血心肌收缩功能异常优于SI。     

彩色多普勒超声显像对下肢皮瓣移植血管的监测

【目的】应用彩色多普勒超声显像（Color Doppler flow imaging CDFI）检测技术对下肢皮瓣移植术前供区血管的检测，了解皮瓣血供分布状况。【方法】采用Acuson soquoia 512及百胜AU4彩色超声检测仪，用彩色多普勒血流成像（CDFI）技术对42例下肢皮瓣内深部动脉干及其肌皮穿支动脉血管的数目、内径、走行方向及分布范围等形态学表现进行检测及血流动力学定量分析。【结果】 彩色多普勒超声对42例拟行移植皮瓣的供皮瓣区动脉血管形态学表现和血流动力学检测，检出供区皮瓣内深部动脉干42条．肌皮穿支动脉82务，均与临床手术中检查动脉的内径，长度及其分布范围相符。上述供区皮瓣深部动脉干与皮支、穿支检出率100％，通过测得下列血流参数：收缩期最大血流速度（Vmax），舒张期最小血流速度（Vmin）、每分血流量（CQ），提示供区血管质量良好与术中检查结果一致，42例移植皮瓣术后全部成活。【结论】彩色多普勒超声是一种直观，无创性检测方法．可以为术前正确选择皮瓣类型．合理设计手术，以及准确评价皮瓣供血状况提供科学依据。     

彩色多普勒探查在带血管蒂皮瓣移植术的应用

本文报告12例带血管蒂皮瓣移植术前彩色多普勒检查结果。皮瓣的主干和皮动脉检出率100％，均经手术证实，诊断符合率100％。本文重点介绍了有关血管的应用解剖和探查方法。研究表明，彩色多普勒是一种简单、直观和准确的诊断方法。     

Skin, wrinkles and botulinum toxin]

OBJECTIVE: To present an up-to-date analysis about the use of botulinum toxin for treating facial lines and wrinkles.Method. - A systematic search of the literature was conducted to select the most recent or relevant publications on this topic, through Medline. RESULTS: Out of the 583 articles retrieved, 90 were finally selected for the study. DISCUSSION: Validity of using botulinum toxin for cosmetic use is demonstrated, together with contra-indications and different methods to objectivate the results. The different available types of toxin are presented and compared. Modalities of preparation, conservation, and waste disposal are detailed. Anatomical bases of muscular facial balance are reviewed, with techniques of injection presented for each site, and also with adjunctive procedures. Complications and side effects are described and analysed. Most complications can be prevented through: perfect knowledge of local anatomy;use of small volumes;orientation of the needle bevel towards the muscle body, injection within the muscle body if thick, more superficial if thin;application of ice on the skin pre- and post-injecting. Adding epinephrin or diluting with xyloca?ne and epinephrin is not commonly used. CONCLUSION: Botulinum toxin has found its way as a major component of the therapeutic armamentarium. Its efficacy for facial rejuvenation has made it extremely popular, but its use does follow strict rules, and should be restricted to soundly trained practitioners.