The role of neutropenia on outcomes of cancer patients with community-acquired pneumonia

Although the presence of neutropenia may predispose cancer patients to develop community-acquired pneumonia, the role of neutropenia on their outcomes has not been investigated. The purpose of the present study was to compare clinical outcomes of cancer community-acquired pneumonia patients with and without neutropenia. Patients with cancer, identified in the Community-Acquired Pneumonia Organization database, were divided into two groups according to the type of cancer and the presence of neutropenia: patients with solid cancer without neutropenia versus those with functional or absolute neutropenia. Among the 3,106 community-acquired pneumonia patients enrolled, 135 had cancer without neutropenia and 75 had cancer with neutropenia. No significant difference was found between patients with and without neutropenia regarding mean time to clinical stability (5.4+/-2.7 versus 4.9+/-2.7 days, respectively), mean length of hospital stay (9.2+/-7.7 versus 9.9+/-9.6 days) and in-hospital mortality (18 versus 15%, respectively). Using a multiple logistic regression model, neutropenia was not associated with mortality in cancer patients when adjusting for significant covariates (odds ratio 1.30). Lack of neutropenia, during the initial evaluation of a cancer community-acquired pneumonia patient, should not be considered an indicator of better clinical outcome.     

生物可吸收依维莫司洗脱冠状动脉支架系统2年随访及多种成像法结果

<正> 生物可吸收支架较金属药物洗脱支架(DES)有可能减少晚期支架内血栓(ST)的发生,因不存在外源性的金属材料和血液相接触,所以不必顾虑血管内皮化延迟或不完全。此外,永久置入的金属支架会影响外科血运重建,堵塞边支血管,妨碍血管的扩张性重塑和血管舒缩反应,还将影响非介人性检查如冠脉多层CT和MRI的成像。作为金属DES     

血红蛋白α、血红蛋白β在卵巢癌患者血清中的表达及意义

目的探讨血红蛋白α(Hb-α)、血红蛋白β(Hb-β)在卵巢癌患者血清中的差异表达。方法2007年10月至2008年4月间在哈尔滨医科大学第四附属医院妇科诊断并经过术后病理证实为浆液性乳头状囊腺癌21例,术前留取静脉血21例,随机对其中10例卵巢浆乳癌Ⅲ期患者术后首次化疗前再留取静脉血10例,共31例血清标本为研究组。取同等条件下正常人血清20例,卵巢良性上皮性肿瘤30例作对照。用ELISA方法定量测定正常人、卵巢良性上皮性肿瘤、卵巢浆乳癌及随机选取的10例卵巢浆乳癌Ⅲ期术后患者血清中Hb-α、Hb-β的质量浓度。结果比较Hb-α、Hb-β浓度:正常人组(18.73±1.03)μg/L,(71.86±2.41)μg/L,与卵巢浆乳癌组(37.05±1.11)μg/L,(86.79±2.31)μg/L比较P<0.05;卵巢良性上皮性肿瘤组(18.10±1.01)μg/L,(71.28±2.22)μg/L,与卵巢浆乳癌组比较P<0.05;正常人组与卵巢良性肿瘤患者组比较P>0.05;比较10例随机的卵巢浆乳癌Ⅲ期术前、术后患者血清中Hb-α、Hb-β的质量浓度平均差值(73.1μg/L,37.5μg/L)P>0....     

B-cell Lymphoma in retrieved femoral heads: a long term follow up

Background  

A relatively high incidence of pathological conditions in retrieved femoral heads, including a group of patients having low grade B-cell lymphoma, has been described before. At short term follow up none of these patients with low-grade B-cell lymphoma showed evidence of systemic disease. However, the long term follow up of these patients is not known.     

Cloning and pharmacological characterization of the dog P2X7 receptor

Background and purpose:

Human and rodent P2X7 receptors exhibit differences in their sensitivity to antagonists. In this study we have cloned and characterized the dog P2X7 receptor to determine if its antagonist sensitivity more closely resembles the human or rodent orthologues.

Experimental approach:

A cDNA encoding the dog P2X7 receptor was isolated from a dog heart cDNA library, expressed in U-2 OS cells using the BacMam viral expression system and characterized in electrophysiological, ethidium accumulation and radioligand binding studies. Native P2X7 receptors were examined by measuring ATP-stimulated interleukin-1β release in dog and human whole blood.

Key results:

The dog P2X7 receptor was 595 amino acids long and exhibited high homology (>70%) to the human and rodent orthologues although it contained an additional threonine at position 284 and an amino acid deletion at position 538. ATP possessed low millimolar potency at dog P2X7 receptors. 2′-&3′-O-(4benzoylbenzoyl) ATP had slightly higher potency but was a partial agonist. Dog P2X7 receptors possessed relatively high affinity for a number of selective antagonists of the human P2X7 receptor although there were some differences in potency between the species. Compound affinities in human and dog blood exhibited a similar rank order of potency as observed in studies on the recombinant receptor although absolute potency was considerably lower.

Conclusions and implications:

Dog recombinant and native P2X7 receptors display a number of pharmacological similarities to the human P2X7 receptor. Thus, dog may be a suitable species for assessing target-related toxicity of antagonists intended for evaluation in the clinic.     

腹腔镜和开腹开窗术治疗肝囊肿的对照性研究

目的：研究腹腔镜和开腹开窗术治疗肝囊肿的疗效比较。方法：收集本院2006年5月～2010年8月外科收治的42例肝囊肿患者,随机分为腹腔镜肝囊肿开窗术22例（A组）,开腹肝囊肿开窗术20例（B组）,对两组手术过程中的住院时间、术中出血量、手术时间、功能恢复时间、症状的复发率以及囊肿的复发率进行统计学分析。结果：两组差异住院时间、术中出血量、手术时间以及功能恢复时间比较,差异有统计学意义（P〈0.05）,两组复发率以及囊肿复发率比较无统计学意义（P〉0.05）。结论：腹腔镜开窗引流术与开腹开窗术比较具有手术时间短、术中出血量少、功能恢复时间较快且住院时间短等优点,在症状复发率及囊肿复发率与开腹手术相似,因此可以逐步取代传统的开腹手术,值得临床广泛推广。     

Low-avidity CD8lo T cells induced by incomplete antigen stimulation in vivo regulate naive higher avidity CD8hi T cell responses to the same antigen

We have previously reported that multiple injections of soluble MHC class I tetramers assembled with wild-type HY peptide induces unresponsiveness to male skin grafts in naive female C57BL/6 (B6) mice. Induction of unresponsiveness is dependent on a population of unresponsive allospecific CD8(lo )T cells. Reduced expression of CD8 acts to limit a T cell response to HY peptide by limiting the avidity window of effective signal transduction. We and others have demonstrated that CD8(lo) T cells are an alternative stable phenotype of CD8alphabeta(+) T cells in vitro and in vivo after antigen stimulation. We show here that CD8(lo) T cells can suppress naive CD8(+) T cell responses to HY antigen in vitro and male skin graft rejection in vivo after adoptive transfer into female recipients. These novel regulatory T cells express surface TGF-beta1 and secrete T cytotoxic 2 cytokines after antigen-specific stimulation. Anti-TGF-beta antibody and latency-associated peptide inhibit the suppressive effects in vitro. We also show that HY-specific memory CD8(+) T cells overcome regulation by CD8(lo) T cells. These data define a novel peripheral regulatory CD8(+ )T cell population that arises after repeated antigen encounter in vivo. These cells have implications in the maintenance of tolerance and memory.     

The effects of CYP2D6 and CYP3A activities on the pharmacokinetics of immediate release oxycodone

Background and purpose:

There is high interindividual variability in the activity of drug-metabolizing enzymes catalysing the oxidation of oxycodone [cytochrome P450 (CYP) 2D6 and 3A], due to genetic polymorphisms and/or drug–drug interactions. The effects of CYP2D6 and/or CYP3A activity modulation on the pharmacokinetics of oxycodone remains poorly explored.

Experimental approach:

A randomized crossover double-blind placebo-controlled study was performed with 10 healthy volunteers genotyped for CYP2D6 [six extensive (EM), two deficient (PM/IM) and two ultrarapid metabolizers (UM)]. The volunteers randomly received on five different occasions: oxycodone 0.2 mg·kg⁻¹ and placebo; oxycodone and quinidine (CYP2D6 inhibitor); oxycodone and ketoconazole (CYP3A inhibitor); oxycodone and quinidine+ketoconazole; placebo. Blood samples for plasma concentrations of oxycodone and metabolites (oxymorphone, noroxycodone and noroxymorphone) were collected for 24 h after dosing. Phenotyping for CYP2D6 (with dextromethorphan) and CYP3A (with midazolam) were assessed at each session.

Key results:

CYP2D6 activity was correlated with oxymorphone and noroxymorphone AUCs and C_max (−0.71 < Spearman correlation coefficient ρs < −0.92). Oxymorphone C_max was 62% and 75% lower in PM than EM and UM. Noroxymorphone C_max reduction was even more pronounced (90%). In UM, oxymorphone and noroxymorphone concentrations increased whereas noroxycodone exposure was halved. Blocking CYP2D6 (with quinidine) reduced oxymorphone and noroxymorphone C_max by 40% and 80%, and increased noroxycodone AUC_∞ by 70%. Blocking CYP3A4 (with ketoconazole) tripled oxymorphone AUC_∞ and reduced noroxycodone and noroxymorphone AUCs by 80%. Shunting to CYP2D6 pathway was observed after CYP3A4 inhibition.

Conclusions and implications:

Drug–drug interactions via CYP2D6 and CYP3A affected oxycodone pharmacokinetics and its magnitude depended on CYP2D6 genotype.     

硫酸镁联合地塞米松治疗爆震性耳聋的临床观察

目的观察硫酸镁联合地塞米松治疗爆震性耳聋的临床疗效。方法选择已确诊为爆震性耳聋患者35例,随机分为联合治疗组20例和糖皮质激素组15例。联合治疗组给予硫酸镁加地塞米松治疗;糖皮质激素组给予地塞米松治疗。两组治疗前、后均行纯音测听、听性脑干反应测听(ABR)检查。对检查结果进行统计学分析。结果治疗后两组患者听力水平都有显著改善,且两组之间对比存在非常显著性差异(P<0.01)。结论硫酸镁联合地塞米松可有效治疗爆震性耳聋,疗效明显优于单纯使用地塞米松。