Dose-Response Evaluation of Levalbuterol Versus Racemic Albuterol in Patients with Asthma

Albuterol, in all marketed forms, is sold as a racemate, composed of a 50:50 mixture of (R)- and (S)-isomers. Racemic albuterol and the single isomer version (R)-albuterol (levalbuterol) were compared in a randomized, double-blind, dose-ranging five-way crossover study in patients (n = 20) with mild persistent to moderate persistent asthma. Placebo, racemic albuterol (2.50 mg), or levalbuterol (0.31, 0.63, or 1.25 mg) were delivered as single, nebulized doses to 5 male and 15 female nonsmoking patients with asthma aged 18-50 years. Serial pulmonary function was assessed at 15-min intervals and mean time to onset of activity and duration of improvement of forced expiratory volume in 1 sec (FEV₁) were measured. In addition, blood chemistries, electrocardiogram (ECG) readings, and patient subjective assessment of adverse symptoms were recorded. Levalbuterol was found to provide significant bronchodilatory activity and was well tolerated. Levalbuterol 1.25 mg provided the greatest increase and duration in FEV₁ improvement, whereas racemic albuterol (2.50 mg) and levalbutero 10.63 mg provided comparable effects. The lower doses of levalbuterol were associated with a less marked effect on heart rate and potassium than racemic albuterol or high-close levalbuterol. These data suggest that 0.63 mg levalbuterol provides honchodilation equivalent to 2.50 mg racemic albuterol with less β-mediated side effects.     

MR imaging of facial nerve enhancement in Bell palsy or after temporal bone surgery

The authors evaluated magnetic resonance (MR) images obtained with intravenously administered gadolinium in ten patients who had facial paralysis and no facial nerve tumor. In patients with either Bell palsy (four patients) or facial paralysis after temporal bone surgery (six patients), intratemporal facial nerve enhancement was seen. Facial nerve enhancement on MR images proved to be a nonspecific finding.     

股骨柄假体表面多孔层孔隙形状改造的动物实验

目的:观察菱形孔隙及方形孔隙两种不同几何形状多孔层设计股骨柄假体的生物学固定效果,分析孔隙几何形状对假体生物学固定的影响。方法:于2003-03/2004-04在中山大学医学部动物中心完成全部实验过程。纳入24只成年杂种犬,雌雄不拘,以随机数字表法均分为2组,即菱形孔隙组及方形孔隙组,各12只。自行设计完成犬骨重建型股骨柄假体,将股骨柄假体近2/3段表层改成两种不同几何形状的粗大多孔层结构,钛丝表面假体,钛丝直径改为1.0mm,孔径加大至5.0mm,孔隙度可达80%。菱形孔隙组钛丝沿股骨假体柄呈螺旋形排列并斜形相交,方形孔隙组钛丝沿股骨假体柄纵横排列并直角相交。均将假体表面孔隙内充填自体股骨头颈骨质制成的骨泥后,行右侧人工股骨头置换术。术后6个月行X射线摄片、组织学检查及生物力学测试,以股骨近端骨吸收情况、新生骨长入深度及孔隙充满度、假体-骨界面最大剪切强度测量为评价指标,了解假体内外成骨和固定情况。结果:菱形孔隙组及方形孔隙组各12只,实验中手术不成功或术后生存不够观察时间的均予实验过程中随时补足,最终每组12只进入结果分析。①组织学观察显示菱形孔隙组多孔层孔隙内最大骨长入深度及孔隙内新生骨平均充盈率均优于方形孔隙组(3000,2450μm;96.2%,71.6%)。②菱形孔隙组假体-骨界面最大剪切强度高于方形孔隙组,差异有显著性意义[(8.57±0.51),(3.15±0.41)N/mm2,P<0.01]。③菱形孔隙组6个月标本肉眼及X射线观察股骨近端无明显骨吸收,优于方形孔隙组;所有实验犬术后伤口缝线任其自行脱落,除1只伤口感染并于术后17d死亡外,余实验犬均伤口愈合良好,未出现不良反应。结论:股骨柄假体表面不同几何形状多孔层设计能影响其生物学固定效果,菱形孔隙设计优于方形孔隙。     

骨关节炎大鼠关节软骨修复与橄榄叶提取物的干预效应

目的:观察橄榄叶提取物对白陶土及鹿角菜胶诱导的大鼠骨关节炎组织炎症的预防作用及对关节软骨的修复作用。方法:试验于2005-11/12在大连医科大学中日合作医药科学研究所进行。实验动物:选择健康雄性SD大鼠80只。实验材料:受试物橄榄叶提取物[由日本国Eisai食品与化学有限公司(日本国东京市)提供]。实验分组及给药:按体质量将大鼠随机分为5组,每组16只。模型对照组,灌胃给予蒸馏水,消炎痛组,灌胃给予消炎痛2mg/kg体质量,其余3组为橄榄叶提取物组,分别给予橄榄叶提取物(活性成分为以羟基酪醇为主的多酚)25,50,100mg/kg体质量灌胃,连续5d。第1天给药后1h,采用白陶土与鹿角菜胶诱发大鼠单发亚急性关节炎。实验评估:①诱发关节炎后1,3,5d,用容积测量法测定每组8只大鼠的左右后肢足跖体积,计算肿胀度,并同时用游标卡尺测定其胫跗骨关节最大径。②诱发关节炎后第5天,测定大鼠足跖伊文思蓝含量。每组的另8只大鼠,在诱发关节炎第5天麻醉后处死,剪下右足跖做组织病理学检查,观察橄榄叶提取物对大鼠骨关节炎中组织炎症的预防作用及对关节软骨的修复作用。结果:80只大鼠全部进入结果分析。①足跖肿胀度及胫跗骨关节径:诱发关节炎后1,3,5d,橄榄叶提取物50mg/kg组和100mg/kg组大鼠的右后足跖肿胀度均明显小于模型对照组大鼠[1d:(46.7±4.2)%,(44.8±6.8)%,(52.5±4.0)%;3d:(40.4±4.8)%,(37.4±5.7)%,(45.0±2.9)%;5d:(34.5±4.8),(31.7±5.3)%,(40.4±4.0)%,P<0.05],橄榄叶提取物25mg/kg体质量组,50mg/kg体质量组,100mg/kg体质量组大鼠的右后胫跗骨关节径与模型对照组大鼠比较差异无显著性(P>0.05)。②足跖伊文思蓝含量:诱发关节炎后第5天,橄榄叶提取物50mg/kg,100mg/kg组大鼠的右后足跖伊文思蓝含量均明显小于模型对照组大鼠(P<0.05)。③组织病理学检查及评分:组织病理学检查可见,与模型对照组比较,橄榄叶提取物50mg/kg组,100mg/kg组大鼠骨关节炎中组织炎症浸润明显减少,软骨组织无破坏,且组织病理学评分也明显小于模型对照组(P<0.05)。结论:橄榄叶提取物在50mg/kg体质量及以上剂量能有效地预防白陶土与鹿角菜胶诱发的大鼠骨关节炎中组织炎症,且对软骨有修复作用。     

Abnormalities in Monocyte Recruitment and Cytokine Expression in Monocyte Chemoattractant Protein 1–deficient Mice

Monocyte chemoattractant protein 1 (MCP-1) is a CC chemokine that attracts monocytes, memory T lymphocytes, and natural killer cells. Because other chemokines have similar target cell specificities and because CCR2, a cloned MCP-1 receptor, binds other ligands, it has been uncertain whether MCP-1 plays a unique role in recruiting mononuclear cells in vivo. To address this question, we disrupted SCYA2 (the gene encoding MCP-1) and tested MCP-1–deficient mice in models of inflammation. Despite normal numbers of circulating leukocytes and resident macrophages, MCP-1^−/− mice were specifically unable to recruit monocytes 72 h after intraperitoneal thioglycollate administration. Similarly, accumulation of F4/80+ monocytes in delayed-type hypersensitivity lesions was impaired, although the swelling response was normal. Development of secondary pulmonary granulomata in response to Schistosoma mansoni eggs was blunted in MCP-1^−/− mice, as was expression of IL-4, IL-5, and interferon γ in splenocytes. In contrast, MCP-1^−/− mice were indistinguishable from wild-type mice in their ability to clear Mycobacterium tuberculosis. Our data indicate that MCP-1 is uniquely essential for monocyte recruitment in several inflammatory models in vivo and influences expression of cytokines related to T helper responses.     

彩色多普勒超声对移植肾急性排斥反应的评价

目的:肾移植的成功与否关键在于及时发现和正确处理排斥反应。探讨无创伤性形态学和血流动力学检查手段彩色多普勒超声在移植肾急性排斥反应中的作用,为临床评估肾移植效果及移植肾功能提供客观的辅助性数据。方法:选择2004-01/2005-12在南京医科大学附属第一医院、江苏省人民医院行同种异体移植肾患者57例,其中经穿刺活检证实或最后临床诊断为急性移植肾排斥反应者22例,未发生排斥反应等并发症的移植肾功能正常者35例,患者均知情同意。采用Philips EnVisor彩色多普勒超声血流显像仪,对急性排斥反应肾移植患者进行二维超声和彩色多普勒血流显像检测,观察排斥反应患者甲基强的松龙冲击治疗前后移植肾脏的大小、形态结构、肾内血管树分布、血流灌注以及各级动脉血流参数(阻力指数,搏动指数)等指标的变化,并与移植肾功能正常患者进行比较。结果:急性排斥反应组2例患者发生严重并发症死亡,进入结果分析急性排斥反应组20例,移植肾功能正常组35例。①发生急性排斥反应时肾移植患者移植肾体积明显大于肾功能正常组(P<0.01);肾实质增厚,皮髓质界限模糊。给予甲基强的松龙冲击治疗后急性排斥反应组患者肾脏厚径显著小于治疗前(P<0.05);肾实质回声减低,皮髓质交界变清。②发生急性排斥反应时肾移植患者移植肾血流阻力指数、搏动指数均显著高于移植肾功能正常组(P<0.01)。治疗后急性排斥反应组患者肾血流阻力指数、搏动指数均显著低于治疗前(P<0.01),与移植肾功能正常组差异无显著性意义(P>0.05)。结论:彩色多普勒超声作为一种简便、经济的无创性技术,对移植肾血流阻力指数、搏动指数的追踪观察可为临床上评估肾移植效果提供较可靠的客观依据,对移植肾急性排斥反应的早期诊断有较高的评估价值。     

Colonic diverticulosis in an infant: A clue to total colonic Hirschsprung disease

Total colonic aganglionosis is a rare phenotype of Hirschsprung disease (HD). While the diagnosis is generally established within the neonatal period there are reports of delayed presentation. In this case, we describe a 9-month old girl with no previous medical or surgical history who presented with a small bowel obstruction. A contrast enema performed as part of the work up demonstrated right sided colonic diverticula with no other anatomical abnormalities. Surgical intervention was required to manage the obstruction and colonic biopsies were consistent with HD. This case highlights the association of the unusual finding of colonic diverticula with total colonic HD in infants.     

Monocyte chemoattractant protein 1-dependent leukocytic infiltrates are responsible for autoimmune disease in MRL-Fas(lpr) mice

Infiltrating leukocytes may be responsible for autoimmune disease. We hypothesized that the chemokine monocyte chemoattractant protein (MCP)-1 recruits macrophages and T cells into tissues that, in turn, are required for autoimmune disease. Using the MRL-Fas(lpr) strain with spontaneous, fatal autoimmune disease, we constructed MCP-1-deficient MRL-Fas(lpr) mice. In MCP-1-intact MRL-Fas(lpr) mice, macrophages and T cells accumulate at sites (kidney tubules, glomeruli, pulmonary bronchioli, lymph nodes) in proportion to MCP-1 expression. Deleting MCP-1 dramatically reduces macrophage and T cell recruitment but not proliferation, protects from kidney, lung, skin, and lymph node pathology, reduces proteinuria, and prolongs survival. Notably, serum immunoglobulin (Ig) isotypes and kidney Ig/C3 deposits are not diminished in MCP-1-deficient MRL-Fas(lpr) mice, highlighting the requirement for MCP-1-dependent leukocyte recruitment to initiate autoimmune disease. However, MCP-1-deficient mice are not completely protected from leukocytic invasion. T cells surrounding vessels with meager MCP-1 expression remain. In addition, downstream effector cytokines/chemokines are decreased in MCP-1-deficient mice, perhaps reflecting a reduction of cytokine-expressing leukocytes. Thus, MCP-1 promotes MRL-Fas(lpr) autoimmune disease through macrophage and T cell recruitment, amplified by increasing local cytokines/chemokines. We suggest that MCP-1 is a principal therapeutic target with which to combat autoimmune diseases.     

Blood transfusion exposure does not influence survival in patients with carcinoma of the breast

There is abundant evidence of immune modulation induced by exposure to blood transfusions. Some studies have demonstrated a detrimental effect of transfusion on the recurrence of malignant disease and survival. We retrospectively studied the impact of blood transfusion exposure on 229 patients with breast cancer who were seen from July 1973 to September 1980, had at least 5 years' follow-up and had been randomized by therapy at the time of diagnosis. The patients were divided into four groups according to transfusion history: Group 1 (111 patients), no transfusion; Group 2 (34 patients), first transfusion after mastectomy; Group 3 (41 patients), first transfusion at mastectomy; and Group 4 (43 patients), first transfusion before mastectomy. All transfused patients received red cells or whole blood or both. At the time of analysis, 124 (54%) of the patients had died. Only Group 2 was statistically associated with decreased survival; recurrence of disease was 85 percent in this group, compared with 53 percent to 61 percent in the other three groups (p = 0.006, log-rank test). In general, Group 2 patients received transfusions because of recurrent disease. We conclude that transfusions before or at mastectomy are not associated with increased recurrence or reduced survival in patients with breast cancer.     

颈动脉内中膜厚度与初诊2型糖尿病视网膜病变的关系

目的:研究发现,糖尿病视网膜病变和动脉粥样硬化终点事件相关。试验拟验证颈动脉内中膜厚度与初诊汉族2型糖尿病患者糖尿病视网膜病变相关危险因素的关系。方法:①试验对象:选择2006-06/2007-06本院住院的初诊2型糖尿病患者187例,男114例,女73例;平均年龄(51±14)岁;平均体质量指数(24.7±4.7)kg/m2。均符合1997年美国糖尿病协会的2型糖尿病诊断标准,排除既往已存在心血管疾病者。患者对治疗及试验均知情同意。根据眼底照相检查结果,将所有受检者分为糖尿病视网膜病变组及非糖尿病视网膜病变组进行统计分析。②试验方法及评估:所有患者询问一般情况,测量颈动脉内中膜厚度以及相关生化指标,对糖尿病视网膜病变相关因素进行单因素及多因素Logistic回归分析。结果:纳入2型糖尿病患者187例,均进入结果分析。单因素Logistic回归分析显示,高血压、糖尿病家族史、颈动脉内中膜厚度、尿白蛋白、低密度脂蛋白胆固醇与糖尿病视网膜病变发生呈显著正相关,多因素Logistic回归分析未见显效因素。结论:单因素回归分析中颈动脉内中膜厚度及其他4项指标与糖尿病视网膜病变相关,而多因素回归分析这些因素未进入主效基因模型。