61例结外鼻型NK/T细胞淋巴瘤患者的临床诊治及预后研究

目的:研究结外鼻型NK/T细胞淋巴瘤的病理特征、临床特点、诊治方案及预后的影响因素。方法:回顾性分析西南医科大学附属医院肿瘤科和血液内科2013年4月-2018年8月收治的61例结外鼻型NK/T细胞淋巴瘤患者临床资料,分析其病理特征,临床特点及诊治方案,并探讨预后的影响因素。结果:中位随访时间为20(3-81)个月,中位年龄48(15-70)岁,男女占比1.5:1,1、3年总生存(OS)率分别为67.2%和26.2%,无进展生存(PFS)率分别为63.9%和24.5%。单因素分析显示,Ki-67百分比影响首程治疗效果;Ann Arbor分期、乳酸脱氢酶、EBER、贫血、IPI指数、B症状、骨髓侵犯、结外累及、单一治疗方式、首次治疗效果是预后的相关因素;多因素分析结果显示,首程缓解是影响预后的独立因素。对于早期患者,接受放疗能获得更多生存率。结论:首程缓解是影响预后的独立因素,早期患者(IE到IIE期)放疗或放化疗联合的疗效优于单纯化疗;晚期患者(IIIE到IVE期)病情进展快,预后差,放疗与化疗2种治疗效果均不理想,需考虑造血干细胞输注、CAR-T等新的治疗方式。     

原发鼻腔NK/T细胞淋巴瘤45例临床分析

目的：探讨原发鼻腔NK/T细胞淋巴瘤的发病情况、临床特点、治疗方案及疗效。方法回顾性分析苏州大学附属第一医院2007年1月～2013年4月收治的鼻腔NK/T细胞淋巴瘤患者45例。结果45例患者均行同期放化疗,其中6例患者后续接受造血干细胞移植。26例患者治疗后达到完全缓解,5年生存率（OS）和无进展生存率（PFS）分别为58.0%、57.2%,ⅠE～ⅡE期分别为64.0%、63.6%,Ⅲ～Ⅳ期为29.2%、30.0%。结论同期放、化疗可有效治疗鼻腔NK/T细胞淋巴瘤,自体造血干细胞移植可进一步改善生存。     

NK/T细胞淋巴瘤误诊分析

目的:了解NK/T细胞淋巴瘤的误诊原因并提出防范措施.方法:对我院误诊的1例NK/T细胞淋巴瘤的临床资料进行回顾性分析并文献复习.结果:本例2年前以周身乏力、食欲缺乏、双下肢有出血点发病.查丙氨酸转氨酶100 u/L.B超检查提示脂肪肝.继之出现双下肢水肿,先后误诊为脂肪肝、紫癜性肾炎.入院前3个月反复发热.全身皮肤出现暗红色出血性皮疹,骨髓穿刺检查示增生活跃,酶谱均增高,后行皮肤活检诊断为NK/T细胞淋巴瘤.结论:NK/T细胞淋巴瘤发病率低,地域性差别大,临床表现多样,易误诊误治.临床应注意与母细胞性NK/T细胞淋巴瘤、皮下脂膜炎样T细胞淋巴瘸相鏊剔,确诊需依靠-临床表现、病理形态学特征及免疫表型三者的有机结合.     

NK细胞活性在诊断继发性噬血细胞综合征中的意义探讨

本研究探讨继发性噬血细胞综合征（hemophagocytic syndrome，HPS）患者外周血NK细胞活性水平及其在早期诊断中的意义。采用LDH释放法检测16例凝似HPS患者和25名正常健康人外周血NK细胞的活性，并将确诊继发性HPS患者的NK细胞活性与正常人NK细胞活性进行比较。结果表明：16例疑似HPS患者中有8例最终确诊为继发性HPS，其NK细胞活性均明显低于正常对照组，两者相比差异有显著统计学意义（p〈0．001），且已确诊患者的NK细胞活性在疾病早期即出现异常。结论：NK细胞活性的检测对于HPS的早期诊断可能具有重要意义。     

结外NK/T细胞淋巴瘤患者的临床特征及预后分析

目的:探讨结外NK/T细胞淋巴瘤患者的临床特点及预后的影响因素.方法:回顾性分析2009年11月至2019年11月本院收治的结外NK/T细胞淋巴瘤患者的临床资料及实验室指标,同时探索影响生存和预后的因素.结果:共收集到47例具有完整临床资料的结外NK/T细胞淋巴瘤患者,中位发病年龄40(12-82)岁,男性多见,男女比...     

自体调节性T细胞可抑制恶性淋巴瘤细胞的增殖

本研究探讨自体调节性T细胞对T细胞淋巴瘤细胞系EIA的作用及其机制。应用免疫磁珠分离法（MACS）分选获得C57BL／6小鼠CD4＋CD25＋T细胞（Treg细胞）,流式细胞术检测细胞纯度及Foxp3表达情况,MTY比色法检测分选的Treg细胞对T细胞淋巴瘤细胞系EL4的体外抑制作用,应用ELISA方法检测TGF—B1和IL-10的含量。结果表明：MACS分选获得CIM＋CD25＋T细胞纯度达91．6％,活细胞比例〉95％,Foxp3表达率为78．9％。MTT比色法证实自体Treg细胞在体外能够明显抑制EIA细胞的增殖（P〈0．05）,且呈细胞因子非依赖性。作者首次证明,自体Treg细胞体外有明显抑制T细胞淋巴瘤细胞系EIA增殖的作用。     

Biological Activity of Autoantibodies From Patients With Thyroid-associated Ophthalmopathy: In Vitro Effects on Porcine Extraocular Myoblasts

To determine whether antibodies to orbital tissue have a pathogenicrole in thyroid-associated ophthalmopathy, the in vitroeffectsof IgG from patients with thyroid-associated ophthalmopathyon porcine extraocular myoblast growth were studied. Growthof primary extraocular myoblast cultures and extraocular myoblastclones was stimulated by patients' IgG, as measured by [³H]thymidineuptake and bromodeoxyuridine incorporation. Myoblasts respondedin a dose-related fashion to increasing concentrations of patients'IgG, and the response was reversed by anti-human IgG. The growthstimulating effect of patients' IgG was relatively specificto extraocular myoblasts, compared to skeletal myoblasts. IndividualIgG samples from 36 patients with ophthalmopathy gave rise tohigher growth responses of cloned extraocular myoblasts, thaneither 31 normal controls (p<0.005), or IgG from 10 patientswith Graves' disease without evidence of ophthalmopathy (p<0.001).Myoblast growth-stimulating antibody did not correlate withthyroid autoantibody levels (thyrotrophin receptor antibodyor thyroid microsomal antibody levels), but correlated significantlywith binding to extraocular muscle membranes (r=0.524, p<0.001).Eye-muscle stimulating antibodies were demonstrable in seraof patients with thyroid-associated ophthalmopathy, and maybe responsible for the enlargement of eye muscle in this disease.     

Long-term Outcome of Extranodal NK/T Cell Lymphoma Patients Treated With Postremission Therapy Using EBV LMP1 and LMP2a-specific CTLs

Extranodal NK/T-cell lymphoma (ENKTCL) is associated with latent Epstein-Barr virus (EBV) infection and frequent relapse even after complete response (CR) to intensive chemotherapy and radiotherapy. The expression of EBV proteins in the tumor provides targets for adoptive immunotherapy with antigen-specific cytotoxic T cells (CTL). To evaluate the efficacy and safety of EBV latent membrane protein (LMP)-1 and LMP-2a-specific CTLs (LMP1/2a CTLs) stimulated with LMP1/2a RNA-transferred dendritic cells, we treated 10 ENKTCL patients who showed complete response to induction therapy. Patients who completed and responded to chemotherapy, radiotherapy, and/or high-dose therapy followed by stem cell transplantation (HDT/SCT) were eligible to receive eight doses of 2 × 10⁷ LMP1/2a CTLs/m². Following infusion, there were no immediate or delayed toxicities. The 4-year overall survival (OS) and progression-free survival (PFS) were 100%, and 90% (95% CI: 71.4 to 100%) respectively with a median follow-up of 55·5 months. Circulating IFN-γ secreting LMP1 and LMP2a-specific T cells within the peripheral blood corresponded with decline in plasma EBV DNA levels in patients. Adoptive transfer of LMP1/2a CTLs in ENKTCL patients is a safe and effective postremission therapeutic approach. Further randomized studies will be needed to define the role of EBV-CTLs in preventing relapse of ENKTCL.     

调节性T细胞抑制小鼠淋巴瘤细胞系EL4体外增殖的研究

本研究探讨自体调节性T细胞对T细胞淋巴瘤细胞系EL4的增殖抑制作用及其机制。应用免疫磁珠分离法(MACS)分选获得C57BL/6小鼠CD4+CD25+T细胞(Treg细胞),流式细胞术检测分选所得的细胞纯度及Foxp3的表达水平,PT-PCR法检测Foxp3 mRNA的表达,3H-TdR掺入法检测分选的Treg细胞对T细胞淋巴瘤细胞系EL4的体外抑制作用,ELISA方法检测抑制实验中细胞因子TGF-β1和IL-10的水平。结果显示,MACS分选获得CD4+CD25+T细胞纯度达94.52%,Foxp3表达比例为84.72%;分选后的细胞用PT-PCR法可检测到Foxp3mRNA的表达;3H-TdR掺入法证实无论有无抗原呈递细胞(APC)或树突状细胞(DC)存在,自体Treg细胞在体外都能明显抑制EL4细胞的增殖(p0.05),APC或DC有可能增强这种抑制作用,且单纯DC对EL4细胞的增殖也有抑制作用;实验中可检测到细胞因子TGF-β1和IL-10。结论:自体Treg细胞在体外能够明显抑制淋巴瘤细胞系EL4细胞的增殖,APC或DC可能增强这种抑制作用,且单纯DC对EL4细胞的增殖也有抑制作用。细胞因子TGF-β1和IL-10是Treg细胞发挥抑制作用的途径之一。     

In Vitro Activity of Ceftazidime-Avibactam Combination in In Vitro Checkerboard Assays

To evaluate the in vitro effects of the combination of ceftazidime and avibactam on the MICs of both compounds, checkerboard assays were performed for 81 clinical strains, including 55 Enterobacteriaceae strains (32 Klebsiella pneumoniae, 19 Escherichia coli, 1 Citrobacter freundii, and 3 Enterobacter cloacae) and 26 strains of Pseudomonas aeruginosa, all with known resistance mechanisms such as extended-spectrum β-lactamases (ESBLs) and carbapenemases, phenotypically or molecularly determined. Phenotypically ceftazidime-resistant strains (n = 69) were analyzed in more detail. For the Enterobacteriaceae strains, a concentration-dependent effect of avibactam was found for most strains with a maximum effect of avibactam at a concentration of 4 mg/liter, which decreased all ceftazidime MICs to ≤4 mg/liter. Avibactam alone also showed antibacterial activity (the MIC₅₀ and MIC₉₀ being 8 and 16 mg/liter, respectively). For the ceftazidime-resistant P. aeruginosa strains, considerable inhibition of β-lactamases by avibactam was acquired at a concentration of 4 mg/liter, which decreased all ceftazidime MICs except one to ≤8 mg/liter (the CLSI and EUCAST susceptible breakpoint). Increasing the concentration of avibactam further decreased the MICs, resulting in a maximum effect for most strains at 8 to 16 mg/liter. In summary, for most strains, the tested addition of avibactam of 4 mg/liter restored the antibacterial activity of ceftazidime to a level comparable to that of wild-type strains, indicating full inhibition, and strains became susceptible according to the EUCAST and CLSI criteria. Based on these in vitro data, avibactam is a promising inhibitor of different β-lactamases, including ESBLs and carbapenemases.     

Platelet Antibodies in Patients With Migraine

The reported decrease of platelet serotonin receptors in patients with migraine could be due to an autoimmune reaction. We, therefore, examined sera from 42 migraineurs without aura, 26 migraineurs with aura, and 107 headache-free blood donors for platelet-reactive antibodies using the platelet adhesion immunofluorescence test, the NIH-lymphocytotoxicity test, and the monoclonal antibody-specific immobilization of platelet antigens test. IgG antibodies against non-HLA class I platelet antigens were found in 9.5% of patients with migraine without aura, 7.6% of patients with migraine with aura, and in 7.5% of controls; IgM antibodies were found in 11.9% of patients with migraine without aura, in 30.8% of patients with migraine with aura, and in 13.1% of controls. Most antibodies ware directed against glycoprotein complexes IIb-IIIa (fibrinogen receptor) or IB-IX (thrombin receptor). Two patients with migraine without aura but no patient with migraine with aura nor any control subject had IgG antibodies of unknown specificity. One patient (2.4%) with migraine without aura and two patients (7.7%) with migraine with aura, as well as 2 controls (1.9%) had IgM antibodies not further specified. The differences in frequency of platelet antibodies of known or unknown specificity in patients with migraine without aura and migraine with aura and controls were not statistically significant. Therefore, our data do not support the hypothesis of a pathophysiologically relevant autoimmune reaction against platelet serotonin receptors in the majority of patients with migraine. We can not exclude the occurrence of antibodies against neuron-specific serotonin receptors.     

In Vitro Activity of Thienamycin

The in vitro activity of thienamycin was tested against 135 aerobic and anaerobic bacteria. The compound was highly active against resistant gram-negative bacilli and penicillin-resistant Straphylococcus aureus. The antianaerobic spectrum of the drug seemed to be comparable to that of metronidazole.     

In Vitro Activity of Netilmicin

The activity of netilmicin against a variety of bacteria was similar to that of gentamicin, sisomicin, and tobramycin, but it was less active than these three drugs against Pseudomonas aeruginosa. Synergy with penicillin G against enterococci was demonstrated.     

In Vitro Activity and Pharmacokinetics in Patients of Cefamandole, a New Cephalosporin Antibiotic

Cefamandole nafate, a new cephalosporin for parenteral use, was evaluated in vitro against 231 recent clinical isolates and in 12 patients. Cefamandole had activity equivalent to cefazolin against Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae. Cefamandole was more active than cephalothin or cefazolin against Proteus mirabilis. Both cefamandole and cefazolin were as active as cephalothin against S. aureus, were slightly more active against K. pneumoniae, and were considerably more active against E. coli. All strains of indole-positive Proteus sp. were inhibited by 6.3 mug of cefamandole per ml but only 20% were inhibited by 25 mug of cefazolin or cephalothin per ml. Eighty-eight percent of Enterobacter sp. was inhibited by 25 mug of cefamandole per ml, but only 20 and 5% were inhibited by the same concentration of cefazolin and cephalothin, respectively. Peak levels of cefamandole ranged from 6.0 to 110 mug/ml in serum and levels ranged from 440 to 16,800 mug/ml in a 4- to 6-h collection of urine after a 500-mg or 1-g intramuscular dose (6.1 to 17.3 mg/kg) in patients with endogenous creatinine clearances of >/=31 ml/min. These levels were done after the first dose, at mid-therapy, and at the end of therapy. There was no evidence of accumulation with the 500-mg or 1-g dose given every 4 to 6 h. The percentage of the dose excreted in the urine within the first 4 to 6 h after administration of cefamandole was >/=43%. The half-life of cefamandole in serum was 49 to 126 min.     

Reduced Activity of the NK Cells from Patients with Cluster Headache and the "In Vitro" Response to β-Interferon

SYNOPSIS
A quantitative increase of leukocyte Leu7+ subset (largely represented by cells with natural killer activity, NK) was observed in the peripheral blood mononuclear cells of patients during the active period of cluster headache (CH). These patients are susceptible to herpes virus infections. In order to ascertain whether or not the quantitative changes in Leu7+ leukocyte subset would correspond to changes of the NK function, the activity of NK cells was investigated in CH patients. Eighteen patients with the episodic form of CH were studied during cluster periods and in painless periods. The control group consisted of 11 healthy volunteers. The results show that the NK activity of CH patients is significantly lower in comparison to that of control values. This impairment appears to be independent of the cluster period.
Since β-IFN has been shown to increase "in vitro" NK cell activity, studies were performed to investigate if β-IFN could restore the limited NK activity found in CH patients. For this purpose the "in vitro" effect of overnight incubation with β-IFN (1000 I.U./ml) was assessed on NK cell activity in CH patients and in the control group. It was found that β-IFN was more effective in increasing NK activity of effector cells collected from CH patients when compared with healthy controls.     

鼻腔NK/T细胞淋巴瘤患者的生存及预后分析

目的:分析鼻腔结外NK/T细胞淋巴瘤(extranodal natural killer/T-cell lymphoma,ENKL)患者的生存及预后状况。方法:选取2012年6月-2018年6月本院初治鼻腔ENKL患者52例。分别采用Kaplan-Meier法、COX比例风险模型对各个因素和预后的关系作单因素及多因素分析。结果:患者中位OS时间为72个月。单因素分析表明,性别、年龄、IPI、ECOG、Hb、临床分期及治疗模式均与鼻腔ENKL患者的OS相关。多因素分析显示,Hb、年龄及临床分期是影响鼻腔ENKL患者OS的独立因素。结论:Hb、年龄及临床分期可用于预测鼻腔ENKL患者的预后。     

Migraine in Patients With Stroke and Antiphospholipid Antibodies

SYNOPSIS
The association between migraine and antibodies against antiphospholipids is controversial. We investigated the prevalence and the clinical feature of migraine in patients with ischemic stroke and antiphospholipid antibodies. Data were obtained from the medical records of 162 consecutive patients with ischemic stroke over a 2-year period. Ten patients with antiphospholipid antibodies were prospectively identified. A history of migraine was present in 6 of these patients and in only 5 of the 152 patients with negative results for antiphospholipid antibodies (chi-square=47.68; P <.0001). In the former, migraine had been for a long time the only clinical problem before the occurrence of the ischemic stroke. These findings suggest that migraine is frequent and can be an early and a prominent symptom in the antiphospholipid antibodies syndrome. Further studies are needed to fully elucidate the association of migraine and antiphospholipid antibodies. A better knowledge of this association could allow an early identification of patients at high risk of stroke.     

In Vitro Activity of Tobramycin and Gentamicin

The in vitro antimicrobial activity of tobramycin and gentamicin was compared against 362 bacterial isolates. The minimal inhibitory concentration (MIC) of tobramycin was fourfold less than the MIC of gentamicin against most of 119 Pseudomonas organisms. Gentamicin and tobramycin had similar in vitro activity against Enterobacteriaceae and Staphylococcus aureus. Proteus rettgeri were commonly resistant to both tobramycin and gentamicin. The 10-mug tobramycin disc separated resistant (MIC >/=5 mug/ml) and susceptible (MIC <5 mug/ml) organisms in 359 of 362 tested. In disc diffusion testing, the tobramycin and gentamicin zone diameters were found to vary significantly with concentrations of magnesium ions in the media employed. The MIC of tobramycin varied with the size of the inoculum, and tobramycin was most effective at a neutral pH.     

In Vitro Activity of LY127935

LY127935 is a unique new beta-lactam antibiotic. Its activity against 536 clinical isolates was studied by using microdilution methods of susceptibility testing and compared with the activities of cefamandole, cefoxitin, and cephalothin. The lowest concentrations required to inhibit at least 90% of strains tested (MIC(90)s) of LY127935 for Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus pneumoniae ranged from 2 to 8 mug/ml. The MIC(90)s for other staphylococci and streptococci were higher. The MIC(90)s for Enterobacteriaceae and Pseudomonas species ranged from 0.12 to 8 mug/ml and 8 to >32 mug/ml, respectively. The MIC(90)s for anaerobes ranged from 2 to >32 mug/ml. As determined by MIC(90)s, LY127935 was consistently the least active antibiotic against facultatively anaerobic gram-positive cocci and the most active against aerobic and facultatively anaerobic gram-negative bacilli. Its position with respect to activity against anaerobes varied from being the most active against Bacteroides fragilis and Clostridium perfringens to the least active against anaerobic cocci. In a population of multidrug-resistant isolates, concentrations of 8 mug or less of LY127935 per ml inhibited 82% of Enterobacteriaceae; concentrations of 32 mug or less per ml inhibited 100% of Enterobacteriaceae and 40% of P. aeruginosa. Increasing the inoculum size by 100-fold did not increase the minimal inhibitory concentrations of LY127935 or cefoxitin but did increase minimal inhibitory concentrations of cefamandole and cephalothin for some Enterobacteriaceae. All four drugs were bactericidal; minimal bactericidal concentrations were the same or one concentration higher than minimal inhibitory concentrations for 91 to 96% of strains tested. The broad spectrum and marked in vitro activity of LY127935 make it a promising new antibiotic.     

Antibacterial Activity of Cinoxacin In Vitro

Cinoxacin is a new synthetic compound similar chemically and in antimicrobial activity to oxolonic acid and nalidixic acid. It is most effective against Escherichia coli and Proteus mirabilis, but at concentrations expected in the urine it is inhibitory for all species of Enterobacteriaceae. Relative to nalidixic acid, cinoxacin has slightly greater inhibitory and bactericidal activity, less inoculum effect probably due to less heterogeneity in the susceptibility of bacterial cells, and less inhibition by high concentrations of serum protein. Both drugs are more active in an acid than an alkaline medium. Glucose can specifically antagonize the inhibitory effect against P. mirabilis. In urine the bactericidal rate and effect are decreased. Resistance to cinoxacin can be developed quickly by serial transfers in vitro. Some nonresistant organisms remained viable in bactericidal drug concentrations. The in vivo importance of the favorable features of cinoxacin must be determined by clinical trials.