Epidemiology of community-acquired Staphylococcus aureus bacteremia.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important nosocomial pathogen which has been isolated with increasing frequency in recent decades. Community-acquired MRSA (CA-MRSA) infections have also become increasingly important in recent years. This study retrospectively analyzed the risk factors, duration of hospitalization, yearly trend and seasonal variation in prevalence, and antibiotic susceptibility of isolates of community-acquired S. aureus (CASA) bacteremia and CA-MRSA bacteremia from patients treated in a teaching hospital in northern Taiwan. A total of 104 clinical isolates of CASA bacteremia were collected between January 1999 and December 2001. Among these, 35 (33.7%) were identified as MRSA. After multivariate analysis, the independent risk factors for developing CA-MRSA bacteremia were diabetes mellitus (p=0.028), chronic obstructive lung disease (p=0.037), and renal insufficiency (p=0.041). Only 6 (17.1%) patients in the MRSA group had no identified risk factors. Most of the isolates of CA-MRSA had a high degree of resistance to most antibiotics, including clindamycin (71.4%), trimethoprim-sulfamethoxazole (65.7%), and chloramphenicol (41.2%). No major trend or seasonal variation in the prevalence was found during the study period. No difference in mortality related to resistance pattern was found. Although CA-MRSA is not the major pathogen in community-acquired bacteremia, it should be included in the differential diagnosis of Gram-positive bacterial bloodstream infection, especially in those patients with risk factors. Early empiric therapy with glycopeptides in these patients may reduce morbidity and mortality.     

Differential effects of (S)- and (R)-enantiomers of albuterol in a mouse asthma model

BACKGROUND: (R)- and (S)-Enantiomers of albuterol likely exert differential effects in patients with asthma. The (R)-enantiomer binds to the beta2-adrenergic receptor with greater affinity than the (S)-enantiomer and is responsible for albuterol's bronchodilating activity. (S)-Albuterol augments bronchospasm and has proinflammatory actions. OBJECTIVE: The study aim was to determine whether the (S)-enantiomer, in contrast to the (R)-enantiomer, has adverse effects on allergic airway inflammation and hyperresponsiveness in a mouse asthma model. METHODS: Mice sensitized to ovalbumin (OVA) intraperitoneally on days 0 and 14 were challenged with OVA intranasally on days 14, 25, and 35. On day 36, 24 hours after the final allergen challenge, the effect of the (R)- and (S)-enantiomers of albuterol (1 mg x kg(-1) x d(-1) administered by means of a miniosmotic pump from days 13-36) on airway inflammation and hyperreactivity was determined. RESULTS: In OVA-sensitized/OVA-challenged mice, (R)-albuterol significantly reduced the influx of eosinophils into the bronchoalveolar lavage fluid and airway tissue. (R)-Albuterol also significantly decreased airway goblet cell hyperplasia and mucus occlusion and levels of IL-4 in bronchoalveolar lavage fluid and OVA-specific IgE in plasma. Although (S)-albuterol significantly reduced airway eosinophil infiltration, goblet cell hyperplasia, and mucus occlusion, it increased airway edema and responsiveness to methacholine in OVA-sensitized/OVA-challenged mice. Allergen-induced airway edema and pulmonary mechanics were unaffected by (R)-albuterol. CONCLUSION: Both (R)- and (S)-enantiomers of albuterol reduce airway eosinophil trafficking and mucus hypersecretion in a mouse model of asthma. However, (S)-albuterol increases allergen-induced airway edema and hyperresponsiveness. These adverse effects of the (S)-enantiomer on lung function might limit the clinical efficacy of racemic albuterol.     

Amplification of MGC2177, PLAG1, PSMC6P, and LYN in a malignant mixed tumor of salivary gland detected by cDNA microarray with tyramide signal amplification

Gene amplifications have been observed in many different tumor cells, and many of these changes are related to tumor pathogenesis. Comparative genomic hybridization (CGH) using metaphase chromosomes can detect changes in chromosome copy number with a resolution of 10-20 Mb. Current advances in CGH analysis in a microarray format allow us to refine such changes down to the gene level. We applied microarray technology to detect novel gene amplification in a malignant mixed tumor of salivary gland. Besides detecting previously known gene amplifications (MDM2 and MYC), we identified four other highly amplified genes located at 8q11.2 approximately q13: MGC2177, PLAG1, PSMC6P, and LYN. The amplification was further validated with real-time quantitative polymerase chain reaction.     

Formoterol provides long-lasting protection against exercise-induced bronchospasm.

BACKGROUND: Patients with exercise-induced bronchospasm (EIB) may benefit from a prophylactic beta2-adrenergic agonist that combines rapid onset with long duration of action. OBJECTIVE: To compare the protective effect against EIB of a single inhaled dose of formoterol powder delivered via the Aerolizer inhaler (Novartis Pharmaceuticals, East Hanover, NJ) with the effect of placebo and albuterol. METHODS: Eighteen patients with EIB were randomized to treatment in a double-blind, placebo-controlled, four-way, crossover study. Seventeen patients completed all four crossover periods. Each patient received in random sequence a single dose of formoterol (12 or 24 microg), albuterol (180 microg), or placebo at intervals of 5 +/- 2 days. Pulmonary function measurements were taken before and after exercise challenge tests (ECTs) at 15 minutes postdosing and at 4, 8, and 12 hours postdosing. RESULTS: Both doses of formoterol produced significantly greater protection against EIB, compared with placebo, at all timepoints (P < or = 0.016). The two doses of formoterol were not significantly different from one another at any time. Protection against EIB with albuterol was clinically significant only for the 15-minute ECT and was statistically superior to placebo for the 15-minute and 4-hour ECTs. Although formoterol and albuterol exhibited a rapid onset of action, formoterol provided longer-lasting protection over the 12-hour observation period. Rescue medication was used substantially less with either dose of formoterol, compared with albuterol or placebo. All treatments were well tolerated. Two-hour postdosing electrocardiograms and vital signs were unremarkable for all study treatments. CONCLUSION: A single dose of formoterol (12 or 24 microg) provides protection against EIB within 15 minutes of dosing and persists for up to 12 hours. Formoterol is safe and well tolerated.     

Persistent monocytosis after intravenous immunoglobulin therapy correlated with the development of coronary artery lesions in patients with Kawasaki disease.

BACKGROUND AND PURPOSE: This study was conducted to investigate whether changes in the complete blood count (CBC)/differential count (DC) and C-reactive protein (CRP) were correlated to Kawasaki disease (KD) with coronary artery lesions (CALs). METHODS: A retrospective analysis was performed of all children with KD at Chang Gung Memorial Hospital at Kaohsiung from 2001 to 2006. KD patients were divided into those with and without CALs for testing of correlations with changes in CBC/DC and CRP levels. RESULTS: A total of 147 patients were enrolled for this analysis. Serial CBC/DC and CRP measurements and echocardiographic data for determination of CAL formation were obtained before and after intravenous immunoglobulin (IVIG) treatment. There were 44 (29%) KD patients having CAL formation (>3 mm in diameter of internal lumen). There was no significant difference in terms of age distribution and major diagnostic criteria between KD patients with and without CALs. Male KD patients, however, had a significantly higher rate of CAL formation (p=0.009). In multivariate logistical regression analysis, persistent monocytosis after IVIG treatment was the only factor significantly correlated to CAL formation (p=0.003). CONCLUSIONS: Of the febrile routine measurements of CBC/DC and CRP in KD, persistent monocytosis after IVIG treatment was correlated to CAL formation. Further studies to clarify the mechanism of monocytosis may help prevent the CALs of KD.     

抗T细胞单克隆抗体对再生障碍性贫血患者TNF和IL—2水平的影响

为探讨抗Ｔ淋巴细胞克隆抗体对再生障碍性贫血患者免疫功能的调节作用，采用放射免疫检测２５例ＡＡ患者ＭｃＡｂ－Ｔ治疗前后血清肿瘤坏死因子和白细胞介素－２（ＩＬ－２）水平及其中１０例周围血单个核细胞体外诱生ＴＮＦ和ＩＬ－２水平的变化。     

Crossing the barrier: Evolution and spread of a major class of mosaic pbp2x in Streptococcus pneumoniae, S. mitis and S. oralis

A paradigm for Streptococcus interspecies gene transfer is represented by the mosaic pbp genes encoding the target enzymes for beta-lactam antibiotics, the penicillin-binding proteins, in Streptococcus pneumoniae. We investigated a collection of oral streptococci from three continents by comprehensive multi-locus sequence typing analysis in order to trace the origin of a mosaic block belonging to a dominant family of mosaic pbp2x implicated in penicillin resistance of S. pneumoniae. One widespread family of mosaic pbp2x occurred in all three distinct clusters of S. pneumoniae, Streptococcus mitis and Streptococcus oralis, documenting independent inter- and intraspecies recombination events. Moreover, potential ancestor genes of this mosaic block could be identified in two penicillin-susceptible S. mitis strains from South Africa and Spain, facilitating the identification of pbp2x mutations relevant for resistance development.     

不同来源乙肝表面抗原的细胞免疫学对比研究

目的　研究不同来源乙肝表面抗原诱导CD8 抗原特异性的细胞毒T淋巴细胞反应(CTL)的差异及T细胞产生细胞因子的能力 ,从而对各种来源乙型肝炎表面抗原 (HBsAg)的免疫原性有更充分的评价。方法　不同来源HBsAg分别免疫BALB c小鼠 ,于免疫后不同时间制备脾脏单个核细胞 (MNC) ,再以相应的HBsAg体外刺激 ,酶联免疫方法 (ELISA)测定细胞因子分泌水平 ;以Na2 5 1CrO4标记靶细胞 ,测定CTL反应活性 ;应用流式细胞仪分析T细胞亚群。结果　HM HBsAg免疫小鼠 10d后的脾细胞产生IFN γ水平最高 ,而在免疫后 2 0d和 2 5d ,IL 2的水平显著高于其它各组 ,CD3 分子脾淋巴细胞显著高于其它各实验组 (P <0 .0 5) ;plasma HBsAg免疫小鼠的脾淋巴细胞产生IFN γ和IL 2水平较低 ,但在免疫 2 5d对P815 HBs的杀伤性最强 ;HM HBsAg和SSC HBsAg免疫后CD4 CD8- 脾淋巴细胞比例显著增高 (P <0 .0 5) ;CD4- CD8 细胞所占百分比各组间及与空白对照组间差异无显著性 (P >0 .0 5)。结论　不同来源HBsAg诱导的细胞免疫反应类型和程度不同     

Endometrial and subendometrial blood flow measured during early luteal phase by three-dimensional power Doppler ultrasound in excessive ovarian responders

BACKGROUND: Impaired implantation in assisted reproduction cycles with high serum estradiol (E(2)) concentrations may be related to suboptimal endometrial perfusion. Endometrial and subendometrial blood flow were compared between excessive responders (serum E(2) on the day of HCG >20 000 pmol/l) and moderate responders (E(2) < or =20 000 pmol/l). METHODS: Three-dimensional (3D) ultrasound examination with power Doppler was performed 2, 4 and 7 days after HCG in 32 patients who did not have embryo transfer in order to measure endometrial thickness, pulsatility index (PI)/resistance index (RI) of uterine vessels, and endometrial volume, vascularization index (VI)/flow index (FI)/vascularization flow index (VFI) of endometrial and subendometrial regions. RESULTS: Excessive responders tended to have lower endometrial and subendometrial VI/VFI on HCG +2 and more absent endometrial/subendometrial blood flow. They had significantly higher endometrial FI and subendometrial VFI than moderate responders on HCG +7. Only in the excessive responder group, uterine PI/RI declined significantly from HCG +2 to HCG +7 and endometrial VI/VFI increased significantly from HCG +4 to HCG +7. CONCLUSION: Changes in uterine Doppler flow indices, and endometrial and subendometrial 3D power Doppler flow indices during the early luteal phase were significantly different between moderate and excessive responders.     

Lactoferrin gene expression is estrogen responsive in human and rhesus monkey endometrium.

We have previously shown that the estrogen responsiveness of the human lactoferrin gene in a transient transfection system is mediated through an imperfect estrogen response element (ERE) and a steroidogenic factor 1 binding element (SFRE) 26 bp upstream from ERE. Reporter constructs containing SFRE and ERE respond to estrogen stimulation in a dose-dependent manner, whereas mutations at either one of the response elements severely impaired the estrogen responsiveness. In this study, we demonstrated that estrogen receptor (ERalpha) binds to the human lactoferrin gene ERE and forms two complexes in an electrophoresis mobility shift assay (EMSA). These complexes could be supershifted by an antibody to ERalpha. We also showed that in normal cycling women, lactoferrin gene expression in the endometrium increases during the proliferative phase and diminishes during the luteal phase. This in-vivo study thus supported the finding from transient transfection experiments that the human lactoferrin gene expression is elevated in an environment with a high level of estrogen. The estrogen effect on lactoferrin gene expression in the rhesus monkey endometrium was studied by Western blotting and immunohistochemistry. The immunohistochemistry results showed that immunoreactive lactoferrin protein was not detectable in the untreated ovariectomized monkey endometrium, was elevated by estrogen treatment, and was suppressed by sequential, combined estrogen plus progesterone treatment. In conclusion, this study has shown that lactoferrin gene expression is responsive to estrogen in primate endometrium.