丙泊酚复合不同剂量阿芬太尼用于无痛人流术的临床观察

目的观察阿芬太尼联合丙泊酚用于无痛人流术的安全性与有效性。方法选择ASAⅠ或Ⅱ级拟在静脉全身麻醉下行无痛人流术患者90例,随机均分为三组:分别静注芬太尼1μg/kg（F1组）、阿芬太尼5μg/kg（F2组）、10μg/kg（F3组）,泵注丙泊酚2.0 mg·kg^-1·min^-1直至改良清醒镇静（MOAA/S）评分为0分为止。记录注药前（T₁）、睫毛反射消失时（T₂）、手术开始时（T₃）、手术开始后1min（T₄）、术毕（T₅）及清醒时（T₆）的MAP、HR、SpO₂、SNAP指数（SI）,各组丙泊酚的总用量、起效时间、手术时间、意识恢复时间、清醒时间,手术过程中体动反应,患者清醒后10、30 min的疼痛VAS评分,记录不良反应的发生率。结果 T₂时F1组S1明显低于F2、F3组,T₃时F2组MAP及SI均明显高于、HR明显快于F1、F3组（P<0.05）,T₂、T₃时F3组的SpO₂明显低于F1组（P<0.05）,但均在正常值范围。F3组丙泊酚总用量明显少于F1与F2组（P<0.05）,F2、F3组起效时间、意识恢复时间、F3组的清醒时间均明显短于F1组（P<0.05）,F2组发生体动反应的例数明显高于F1、F3组（P<0.05）。结论阿芬太尼10μg/kg与丙白酚联合用于无痛人流术是安全有效的。     

Use of disposable negative pressure wound therapy on split‐thickness skin graft recipient sites for peripheral arterial disease foot wounds: A case report

Split‐thickness skin graft (STSG) helps to promote healing of wounds by providing a viable soft tissue cover. However, the success of which is influenced by how well it takes to the recipient site. Studies have demonstrated that negative pressure wound therapy (NPWT) is an excellent modality to promote graft survival. Technological advancements have made possible the invention of disposable, ultraportable, and mechanically operated versions for improved user experience. Alas, little has been discussed about their benefits on STSG. Therefore, the purpose of this case report is to highlight the effective use of disposable NPWT on freshly applied STSG. We report here a novel use of the disposable NPWT (SNAP therapy system) for STSG recipient sites in two patients with peripheral arterial disease (PAD) foot wounds. In both patients, there was 100% STSG uptake, and the lightweight disposable NPWT system makes for a more cost‐effective and comfortable experience for patients. Disposable NPWT may be a feasible alternative to conventional NPWT to aid with STSG uptake for PAD foot wound recipient sites.     

肌电图对腰神经后根节段定位作用的实验研究

目的:探讨应用肌电图行大鼠腰神经后根节段定位的方法。方法:通过电生理的方法,依次电刺激L3￣L5脊神经后根,分别记录大鼠双侧下肢主要肌肉的肌电图像,测量最早出现的感觉神经动作电位(SNAP)最大波幅值。结果:刺激L3脊神经后根,于股四头肌记录到的波幅峰值(480.8±255.9μV)显著高于其它各组肌肉(P<0.01)。刺激L4脊神经后根,于下肢四组肌肉记录到的CMAP最大波幅平均值均>100μV,其中在股四头肌(305.2±131.5μV)、胫骨前肌(340.2±310.4μV)记录到的波幅峰值显著高于在股二头肌(142.4±144.7μV)、腓肠肌(138.2±127.6μV)记录到的波幅峰值(P<0.01)。刺激L5脊神经后根,于股二头肌(377.5±264.4μV)、腓肠肌(168.4±126.7μV)记录到的波幅峰值显著高于其它各肌群记录到的波幅峰值(P<0.01)。结论:电刺激不同脊神经后根,在大鼠下肢不同肌肉记录到的SNAP的波幅峰值存在差异,综合分析记录到的SNAP的波幅峰值,可作为腰神经后根节段定位的参考。     

A comparison of the SNAP II and BIS XP indices during sevoflurane and nitrous oxide anaesthesia at 1 and 1.5 MAC and at awakening

Background. Monitoring level of consciousness during anaesthesia,with the ability to predict the intentional or unintentionalreturn to consciousness, is desirable. The purpose of this studywas to compare two processed electroencephalographic depth ofanaesthesia monitors (SNAP II^TM and BIS XP^TM) during sevofluraneand sevoflurane/nitrous oxide anaesthesia. Methods. In total, 42 subjects received an interscalene block,followed by general anaesthesia with sevoflurane or sevoflurane/nitrousoxide. The indices were recorded at baseline, at 1.5 and 1.0minimum alveolar concentration (MAC) equivalents, and duringemergence. Results. The SNAP and BIS indices decreased from baseline at1.5 and 1.0 MAC equivalents, but there was no difference withingroups between subjects who received nitrous oxide and thosewho did not. The SNAP index returned to baseline by 1 min beforeawakening and was higher than baseline at eye opening, but theBIS index remained below baseline at awakening. There was abias of –1 (95% CI: –3 to 1) between the SNAP andBIS at baseline; this increased to 21 (95% CI: 19–23)during maintenance of anaesthesia and was 6 (95% CI: 4–8)at awakening. Conclusions. The SNAP index tracks loss of consciousness andemergence from sevoflurane and sevoflurane/nitrous oxide anaesthesia.There is significant bias between the SNAP and BIS indices andtherefore, the indices are not interchangeable. The SNAP indexreturns to baseline before awakening, whereas the BIS indexremains below baseline at awakening, suggesting that the SNAPindex may be more sensitive to unintentional awareness.      

A Refined Guinea Pig Model of Foot‐and‐Mouth Disease Virus Infection for Assessing the Efficacy of Antiviral Compounds

An antiviral containment strategy for foot‐and‐mouth disease (FMD) outbreaks could support or replace current contingency plans in case of an outbreak in Europe and could spare many healthy animals from being pre‐emptively culled. Recently, substantial progress has been made towards the development of small molecule drugs that inhibit FMD virus (FMDV) replication in vitro. For the initial in vivo evaluation of antiviral lead molecules, a refined FMDV‐infection model in guinea pigs (GP) is herewith described. This GP model was validated by demonstrating the antiviral effect of T‐1105 (an influenza virus inhibitor with reported activity against FMDV). Sixteen animals were orally administered with T‐1105 twice daily (400 mg/kg/day) for five consecutive days and inoculated intraplantarly with 100 GPID₅₀ of the GP‐adapted FMDV strain O₁ Manisa 1 h after the first administration. The efficacy of T‐1105 was compared with that of prophylactic vaccination with a highly potent double‐oil emulsion‐inactivated O₁ Manisa vaccine. Ten animals received a single, full (2 ml) cattle vaccine dose and were inoculated 3 weeks later. Fourteen T‐1105‐treated and all vaccinated GP were completely protected from generalization of vesicular lesions. At 2 dpi, viral RNA was detected in serum of 9/16 T‐1105‐treated and of 6/10 vaccinated animals. At 4 dpi, viral RNA was detected in serum, organs and oral swabs of half of the T‐1105‐treated animals and only in the serum of 1/10 of the vaccinated animals. Mean viral RNA levels in serum and organs of T‐1105‐treated and vaccinated animals were reduced compared to untreated controls (P < 0.01). T‐1105 conferred a substantial clinical and virological protection against infection with O₁ Manisa, similar to the protection afforded by vaccination. These results validate the suitability of the enhanced GP model for the purpose of initial evaluation of inhibitors of FMDV replication and illustrate the potential of selective inhibitors of viral replication to control FMD outbreaks.     

Inducible expression of a prostate cancer-testis antigen, SSX-2, following treatment with a DNA methylation inhibitor

BACKGROUND: Active immunotherapies are one approach being developed as novel treatments for prostate cancer. Critical to the success of these therapies is the identification of appropriate target antigens. We have been seeking to identify immunologically recognized proteins, cancer-testis antigens (CTA) in particular, in patients with prostate cancer that would be rational target antigens. METHODS: Using a previously reported panel of 29 different CTA, we used sera from 98 patients with prostate cancer and 50 healthy male blood donor controls to detect CTA-specific IgG. We then further evaluated the expression of one antigen, SSX-2, in prostate cancer cell lines and tissues. RESULTS: We identified IgG specific for NY-ESO-1, LAGE-1, NFX-2, and SSX-2 in at least 1/98 individuals with prostate cancer. We demonstrated that SSX-2 is a prostate CTA, and its expression is associated with metastatic prostate cancer. In addition, we report that the treatment of at least two human prostate cancer cell lines with the DNA methylation inhibitor 5-aza-2'-deoxycytidine induced the expression of SSX-2. In contrast, treatment of a normal prostate epithelial cell line (RWPE-1) with 5-aza-2'-deoxycytidine did not induce SSX-2 expression. CONCLUSIONS: Our findings suggest that SSX-2 could be further pursued as an immunotherapeutic target in prostate cancer, and that treatment with 5-aza-2'-deoxycytidine could be exploited to modulate antigen expression in combination with immunotherapeutic approaches.     

Dominance of CD4+ lymphocytic infiltrates with disturbed effector cell characteristics in the tumor microenvironment of prostate carcinoma

BACKGROUND: Prostate cancer is the most common cancer of men in the Western world. Despite the over-expression of tumor-associated antigens, like PSA or PSMA, immune activation is inefficient. The goal of this investigation was to assess in situ characteristics of prostate cancer-infiltrating lymphocytes and to determine their activation status and effector function. METHODS: We compared 17 carcinoma containing tissues, four benign prostatic hyperplasia tissues and eight healthy prostate tissues regarding lymphocyte subset composition, locoregional distribution, and functional status using immunohistological staining of cryopreserved tissues. For determination of lymphocyte subsets, serial sections were stained with CD3, CD4, and CD8 antibodies. Activation status and effector function were studied using CD69, interferon-gamma (IFN gamma), perforin, and CD3 zeta chain antibodies. T-cell-receptor repertoire (TCR) analysis was made to determine the complexity of infiltrating lymphocytes. RESULTS: CD3+, CD4+, and CD69+ T lymphocytes were prominent in tissues derived from patients with prostate carcinoma. CD8+ lymphocytes were significantly less than CD4+ lymphocytes. IFN gamma and perforin were downregulated on infiltrating lymphocytes compared to cells of healthy prostate tissue. Very few lymphocytes were detected within cancerous lesions whereas surrounding tissues showed extensive lymphocyte cluster formation. The TCR repertoire of infiltrating lymphocytes was broad and similar to that of healthy prostate tissue, giving no evidence for specific lymphocyte recruitment. CONCLUSIONS: In the prostate cancer microenvironment, CD4+ T lymphocytes dominated while CD8+ T cells were sparse. The lymphocytes exhibited signs of disturbed effector function. Consequently, the immune response against autologous tumor cells is likely to be inefficient in controlling tumor growth.     

Epidemiological Patterns of Foot‐and‐Mouth Disease Worldwide

Foot‐and‐Mouth Disease (FMD) is a clinical syndrome in animals due to FMD virus that exists in seven serotypes, whereby recovery from one sero‐type does not confer immunity against the other six. So when considering intervention strategies in endemic settings, it is important to take account of the characteristics of the different serotypes in different ecological systems. FMD serotypes are not uniformly distributed in the regions of the world where the disease still occurs. For example, the cumulative incidence of FMD serotypes show that six of the seven serotypes of FMD (O, A, C, SAT‐1, SAT‐2, SAT‐3) have occurred in Africa, while Asia contends with four sero‐types (O, A, C, Asia‐1), and South America with only three (O, A, C). Periodically there have been incursions of Types SAT‐1 and SAT‐2 from Africa into the Middle East. This paper describes the global dynamics for the seven sero‐types and attempts to define FMD epidemiological clusters in the different regions of the world. These have been described on a continent by continent basis. The review has reaffirmed that the movement of infected animals is the most important factor in the spread of FMD within the endemically infected regions. It also shows that the eco‐system based approach for defining the epidemiological patterns of FMD in endemic, which was originally described in South America, can apply readily to other parts of the world. It is proposed that any coordinated regional or global strategy for FMD control should be based on a sound epidemiological assessment of the incidence and distribution of FMD, identifying risk sources as either primary or secondary endemic eco‐systems.     

Excellent Clinical Outcomes From a National Donation‐After‐Determination‐of‐Cardiac‐Death Lung Transplant Collaborative

Donation‐after‐Determination‐of‐Cardiac‐Death (DDCD) donor lungs can potentially increase the pool of lungs available for Lung Transplantation (LTx). This paper presents the 5‐year results for Maastricht category III DDCD LTx undertaken by the multicenter Australian National DDCD LTx Collaborative. The Collaborative was developed to facilitate interaction with the Australian Organ Donation Authority, standardization of definitions, guidelines, education and audit processes. Between 2006 and 2011 there were 174 actual DDCD category III donors (with an additional 37 potentially suitable donors who did not arrest in the mandated 90 min postwithdrawal window), of whom 71 donated lungs for 70 bilateral LTx and two single LTx. In 2010 this equated to an “extra” 28% of donors utilized for LTx. Withdrawal to pulmonary arterial flush was a mean of 35.2 ± 4.0 min (range 18–89). At 24 h, the incidence of grade 3 primary graft dysfunction was 8.5%[median PaO₂/FiO₂ ratio 315 (range 50–507)]. Overall the incidence of grade 3 chronic rejections was 5%. One‐ and 5‐year actuarial survival was 97% and 90%, versus 90% and 61%, respectively, for 503 contemporaneous brain‐dead donor lung transplants. Category III DDCD LTx therefore provides a significant, practical, additional quality source of transplantable lungs.     

Complex functions of mutant p53 alleles from human prostate cancer

BACKGROUND: Few studies have used multiple assays to examine the functionality of mutant p53 in prostate cancer (CaP). We employed seven functional assays to study 16 representative mutant p53 alleles, six from localized and ten from metastatic CaP. METHODS: Yeast assays were employed to determine loss of function (LOF), partial function (PF), and dominant-negative status. Assays using p53-null Saos2 cells were used to determine whether mammalian cells transfected with mutant p53 could up-regulate the MDR-1 or PCNA promoters, alter IL-6 expression or confer the ability to grow in soft agar. As a further test of gain of function (GOF), p53-null PC3 cells stably transfected with these mutant p53 alleles were examined for cell cycle distributions. RESULTS: All 16 mutant p53 alleles demonstrated either total or partial LOF. All but one allele also had at least one gain of function; however, the pattern of GOF was different for each mutant allele. Alleles derived from both localized and metastatic CaP had similar GOF characteristics; however, only alleles from metastatic disease had significantly increased S-phase fractions. CONCLUSIONS: Different mutant p53 alleles from CaP had different, complex functional profiles. The lack of predictable patterns for these alleles suggest that each mutation may uniquely affect p53 function.     

Impact of dysphagia on quality-of-life in nasopharyngeal carcinoma

BACKGROUND: Little is known about dysphagia or quality of life (QOL) in patients treated for nasopharyngeal carcinoma (NPC). The aim of this study was to determine the impact of dysphagia on QOL in patients treated for NPC as measured by two standard tools, the University of Washington Quality-of-Life Questionnaire(1) (UW-QOL) and the Swallow Quality-of-Life Questionnaire(3) (SWAL-QOL). METHODS: This is a cross-sectional survey of 59 consecutive disease-free survivors of NPC attending the head and neck cancer clinic at the National University Hospital, Singapore. The UW-QOL and SWAL-QOL underwent minor modification and were translated into Mandarin. A linear regression analysis was performed to identify significant predictors of health-related QOL. RESULTS: Fifty-one patients (86%) responded; of these, 43 had self-reported swallowing difficulties. On the UW-QOL, respondents indicated the three most important issues to be swallowing (59%), hearing (45%), and saliva/dry mouth (41%). Respondents with swallowing difficulty reported a lower UW-QOL composite score (p = .002) and a lower health-related QOL score (HR-QOL) than those without swallowing difficulty (p = .004). Self-reported swallowing difficulty predicted a lower HR-QOL score (p = .004). A longer time since treatment predicted a better score in HR-QOL (p = .024). A lower score in fatigue predicted a lower HR-QOL score (p = .001). CONCLUSIONS: Swallowing difficulties negatively impact QOL. It is recommended that future QOL studies aimed specifically at swallowing function in NPC use a swallowing specific questionnaire (eg, SWAL-QOL) in addition to a head and neck-specific measure. Further research is needed to look at the adaptation and usefulness of swallowing-specific QOL surveys for use with people treated for NPC.     

Role of Toll‐like receptor 4 signaling in cutaneous chronic graft‐versus‐host disease

Cutaneous damage is one of the characterized manifestations in chronic graft‐versus‐host disease (cGVHD). When local effective immunity in the skin is altered to a dysimmune reaction, cutaneous injuries occur. Toll‐like receptor 4 signaling is regarded as a central mediator of inflammation and organ injury. In this study, we found that TLR4 mRNA in peripheral blood from patients with cutaneous cGVHD was markedly increased compared with that from non‐GVHD patients and healthy controls. In addition, NF‐κB expression, TLR4 downstream signaling, and TLR4‐mediated cytokines, including IL‐6 and ICAM‐1, were upregulated. Moreover, ICAM‐1 was widely distributed in skin biopsies from patients with cutaneous cGVHD. We also found that LPS induced TLR4‐mediated NF‐κB activation and IL‐6 and ICAM‐1 secretion in human fibroblasts in vitro. Thus, TLR4, NF‐κB, IL‐6, and ICAM‐1 contribute to the inflammatory response that occurs in cutaneous cGVHD, indicating the TLR4 pathway may be a novel target for cutaneous cGVHD therapy.     

The institution of a Multi‐disciplinary Italian Breast Unit: Reflections of the first psychosocial research study results on distress and quality of life

Breast cancer affects patients both emotionally and physically. It is time to consider distress as the sixth vital sign in breast cancer patients in Europe. Between 2012 and 2015, our EUSOMA‐certified multi‐disciplinary group conducted a study on emotional distress and quality‐of‐life in breast cancer patients at diagnosis, and observed their trend over the first 8 months of treatment. One hundred and forty‐nine patients concluded the program. The psycho‐oncologist and the breast nurses gave out SF36, Hospital Anxiety and Depression Scale and Distress Thermometer. Our Italian data go along with the reported literature on distress and quality‐of‐life. Despite modern advances, experiencing breast cancer impacts on overall quality‐of‐life.     

The effect of drilling and screw fixation of the growth plate—an experimental study in rabbits

Injury of the growth plate is a specific problem in traumatology and can cause limb deformity and length discrepancy as a result of growth arrest. The purpose of this study was to evaluate alterations of the growth plate after artificially created injuries. A total of 14 New Zealand White rabbits were used for this experiment. The right and left ulna of each animal was used resulting in a total of 28 ulnae. In six animals drill holes were driven into the growth plate either from the distal/epiphyseal side or from the proximal/metaphyseal side of the physis. In six animals a fracture of the distal ulna corresponding to a Salter–Harris fracture type IV was created. This fracture was fixed by screws from either the epiphyseal or the metaphyseal side. Two animals served as controls. Histologic and radiologic examinations were performed to evaluate the growth process at 1, 2, 4, and 12 weeks following surgery. Drilling or fixation of the growth plate from the metaphyseal side resulted in temporary growth disturbance which was compensated within a short time. In contrast fixation from the epiphyseal side caused severe growth disturbances. Based on our findings K‐wires or screws should be inserted from the metaphyseal side and be placed in the center of the growth plate. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1834–1839, 2011     

Interleukin-4 and interleukin-13 potentiate interleukin-1 induced secretion of interleukin-6 in human osteoblast-like cells.

Formation of interleukin-6 (IL-6) in osteoblasts and bone marrow stromal cells is believed to regulate osteoclast recruitment. The anti-inflammatory cytokines interleukin-4 and -13 (IL-4 and IL-13) stimulate IL-6 production in human osteoblasts. We investigated the relative potencies, and synergistic effects, between IL-4, IL-13 and interleukin-1 (IL-1) on IL-6 formation in human osteoblast-like cells. Isolated human osteoblast-like cells were incubated for 72 h in the presence of various concentrations of IL-4, IL-13 and IL-1, and IL-6 secretion was measured by ELISA. All cytokines stimulated the secretion of IL-6. The rank order of potency was IL-1>IL-4>IL-13. There were no additive or synergistic effects between IL-4 and IL-13. However, co-stimulation with IL-1 and IL-4 resulted in a marked synergistic effect on IL-6 secretion. Co- stimulation with IL-1 and IL-13 gave a minor synergistic effect. In conclusion, IL-4/13 synergistically potentiates IL-1 induced secretion of IL-6 in human osteoblast-like cells.