乳胶凝集试验快速诊断新生儿B群链球菌败血症

目的:探讨乳胶凝集试验在诊断新生儿B群链球菌(GBS)败血症中的作用。方法:174例疑有败血症的新生儿生后即作外耳道、脐部拭子培养及涂片镜检,胃液培养和血培养,并均采用乳胶凝集试验检测患儿尿中的GBS抗原。根据是否有GBS败血症将患儿分成两组:GBS败血症组(18例)及无GBS败血症组(156例)。将两组乳胶凝集试验结果作比较。结果:GBS败血症组有16例乳胶凝集试验阳性;无GBS败血症组有3例阳性。乳胶凝集试验对GBS败血症的诊断敏感性为88.9%,特异性为98.1%,假阳性率为1.9%。结论:乳胶凝集试验对新生儿GBS败血症的诊断具有重要意义,该方法敏感性和特异性均高,且简便、快速,值得推广应用。     

胆汁反流性胃炎、反流性食管炎与幽朗螺杆菌的关系探讨

目的：探讨幽门螺杆菌(Hp)与胆汁反流性胃炎(BRG)、反流性食管炎(RE)的关系。方法：对192例病人作胃镜检查，并对胃或食管粘膜分别作快速尿素酶试验和病理学妇科白带涂片快速染色法(CTB)，进行分级。结果：BRG患者的Hp感染率为88．88％(96／108)，RE患者的Hp感染率为35．71％(30／84)，BRG组Hp感染率明显高于RE组，差别有显著意义；BRG患者CTB分级较RE高，差别有显著意义。Hp阳性RE患者胃镜分级、病理程度与Hp阴性组比较，差别无显著意义。结论：胆汁反流性胃炎与幽门螺杆菌感染有密切关系，而反流性食管炎与幽门螺杆菌的关系不确定。     

Comparison between successful and failed sit-to-stand trials of a patient after traumatic brain injury

OBJECTIVE: To compare the peak whole-body center of mass (COM) velocities and joint angular contributions in successful and unsuccessful sit-to-stand (STS) trials in a subject with traumatic brain injury (TBI). DESIGN: Single-case study. SETTING: Motion research laboratory. PARTICIPANT: A 24-year-old man who was 3.5 years post-TBI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Peak horizontal and vertical velocities of the whole-body COM and peak angular velocities of the ankle, knee, hip, and shoulder joints. RESULTS: The peak whole-body COM vertical velocity was significantly lower in the unsuccessful STS trials. Angular velocities at the hip, knee, ankle, and shoulder joints in successful trials exceeded those in unsuccessful trials (P<.001). The subject's peak knee extension velocity was the single major predictor of the peak whole-body COM vertical velocity (r(2)=.90). Knee extension angular velocities greater than 3.25 radian/s were associated with successful STS trials. Knee extension angular velocities between 2.75 and 3.25 radian/s were associated with successful rising 50% of the time; the subject had no success in rising when velocities were less than 2.75 radian/s. CONCLUSIONS: For this subject, sit-back failures occurred in STS attempts characterized by peak whole-body COM vertical velocities that were lower than those generated in successful rising trials. These unsuccessful rising attempts were primarily the result of the subject's inability to generate sufficient knee extension angular velocity.     

生血胶囊的毒理学研究

目的本研究观察小鼠和大鼠口服生血胶囊的急性毒性和长期毒性反应,为临床用药提供参考。方法取健康小鼠和大鼠各30只,灌胃给药,2次/d,每次剂量分别为24和16 g/kg,给药后观察14 d,记录动物死亡及不良反应症状,取健康SD大鼠160只,随机分为低、中、高(0.5、2.5、5.0 g/kg)3个剂量组和一个对照组。灌胃,2次/d,每次10 ml/kg,连续26周。用药13周、26周和停药4周后分别取样进行血液学、血液生化学、脏器重量及重量指数,病理组织学检查。结果生血胶囊对小鼠和大鼠的口服最大给药量分别大于24和16 g/kg,该剂量是临床成人拟推荐用药剂量(0.08 g/kg)的240和160倍;长期毒性实验中各组大鼠的一般状况、体质量、血液学指标、血液生化学指标及主要脏器系数与对照组比较未见显著差异和异常改变;肉眼观察服药组心、肝、脾、肺、肾等脏器外观形态、颜色均无异常改变,光镜检查也未见各脏器组织结构和细胞形态异常。结论在推荐临床剂量下服用生血胶囊是安全可靠的。     

The synthetic caged garcinia xanthone cluvenone induces cell stress and apoptosis and has immune modulatory activity

Several caged Garcinia xanthone natural products have potent bioactivity and a documented value in traditional Eastern medicine. Previous synthesis and structure activity relationship studies of these natural products resulted in the identification of the pharmacophore represented by the structure of cluvenone. In the current study, we examined the anticancer activity of cluvenone and conducted gene expression profiling and pathway analyses. Cluvenone was found to induce apoptosis in T-cell acute lymphoblastic leukemia cells (EC?? = 0.25 μmol/L) and had potent growth-inhibitory activity against the NCI60 cell panel, including those that are multidrug-resistant, with a GI?? range of 0.1 to 2.7 μmol/L. Importantly, cluvenone was approximately 5-fold more potent against a primary B-cell acute lymphoblastic leukemia compared with peripheral blood mononuclear cells from normal donors, suggesting that it has significant tumor selectivity. Comparison of cluvenone's growth-inhibitory profile to those in the National Cancer Institute database revealed that compounds with a similar profile to cluvenone were mechanistically unlike known agents, but were associated with cell stress and survival signaling. Gene expression profiling studies determined that cluvenone induced the activation of mitogen-activated protein kinase and NrF2 stress response pathways. Furthermore, cluvenone was found to induce intracellular reactive oxygen species formation. Lastly, the modulation in the expression of several genes associated with T cell and natural killer cell activation and function by cluvenone suggests a role as an immune-modulator. The current work highlights the potential of cluvenone as a chemotherapeutic agent and provides support for further investigation of these intriguing molecules with regard to mechanism and targets.     

Regulation of pulmonary fibrosis by chemokine receptor CXCR3

CXC chemokine receptor 3 (CXCR3) is the receptor for the IFN-gamma-inducible C-X-C chemokines MIG/CXCL9, IP-10/CXCL10, and I-TAC/CXCL11. CXCR3 is expressed on activated immune cells and proliferating endothelial cells. The role of CXCR3 in fibroproliferation has not been investigated. We examined the role of CXCR3 in pulmonary injury and repair in vivo. CXCR3-deficient mice demonstrated increased mortality with progressive interstitial fibrosis relative to WT mice. Increased fibrosis occurred without increased inflammatory cell recruitment. CXCR3 deficiency resulted in both a reduced early burst of IFN-gamma production and decreased expression of CXCL10 after lung injury. We identified a relative deficiency in lung NK cells in the unchallenged CXCR3-deficient lung and demonstrated production of IFN-gamma by WT lung NK cells in vivo following lung injury. The fibrotic phenotype in the CXCR3-deficient mice was significantly reversed following administration of exogenous IFN-gamma or restoration of endogenous IFN-gamma production by adoptive transfer of WT lymph node and spleen cells. Finally, pretreatment of WT mice with IFN-gamma-neutralizing Ab's enhanced fibrosis following lung injury. These data demonstrate a nonredundant role for CXCR3 in limiting tissue fibroproliferation and suggest that this effect may be mediated, in part, by the innate production of IFN-gamma following lung injury.     

High-resolution CT for identify patients with smear-positive, active pulmonary tuberculosis

Purpose

This study evaluates the use of high-resolution computed tomography (HRCT) to differentiate smear-positive, active pulmonary tuberculosis (PTB) from other pulmonary infections in the emergency room (ER) setting.

Methods

One hundred and eighty-three patients diagnosed with pulmonary infections in an ER were divided into an acid fast bacillus (AFB) smear-positive, active PTB group (G1 = 84) and a non-AFB smear-positive, pulmonary infection group (G2 = 99). HRCT images from a 64-Multidetector CT were analyzed, retrospectively, for the morphology, number, and segmental distribution of pulmonary lesions.

Results

Utilizing multivariate analysis, five variables were found to be independent risk factors predictive of G1: (1) consolidation involving the apex segment of right upper lobe, posterior segment of the right upper lobe, or apico-posterior segment of the left upper lobe; (2) consolidation involving the superior segment of the right or left lower lobe; (3) presence of a cavitary lesion; (4) presence of clusters of nodules; (5) absence of centrilobular nodules. A G1 prediction score was generated based on these 5 criteria to help differentiate G1 from G2. The area under the receiver operating characteristic (ROC) curve was 0.96 ± 0.012 in our prediction model. With an ideal cut-off point score of 3, the specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) are 90.9%, 96.4%, 90.0% and 96.8%, respectively.

Conclusion

The use of this AFB smear-positive, active PTB prediction model based on 5 key HRCT findings may help ER physicians determine whether or not isolation is required while awaiting serial sputum smear results in high risk patients.     

A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis

Familial tumoral calcinosis is characterized by ectopic calcifications and hyperphosphatemia due to inactivating mutations in FGF23 or UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3). Herein we report a homozygous missense mutation (H193R) in the KLOTHO (KL) gene of a 13-year-old girl who presented with severe tumoral calcinosis with dural and carotid artery calcifications. This patient exhibited defects in mineral ion homeostasis with marked hyperphosphatemia and hypercalcemia as well as elevated serum levels of parathyroid hormone and FGF23. Mapping of H193R mutation onto the crystal structure of myrosinase, a plant homolog of KL, revealed that this histidine residue was at the base of the deep catalytic cleft and mutation of this histidine to arginine should destabilize the putative glycosidase domain (KL1) of KL, thereby attenuating production of membrane-bound and secreted KL. Indeed, compared with wild-type KL, expression and secretion of H193R KL were markedly reduced in vitro, resulting in diminished ability of FGF23 to signal via its cognate FGF receptors. Taken together, our findings provide what we believe to be the first evidence that loss-of-function mutations in human KL impair FGF23 bioactivity, underscoring the essential role of KL in FGF23-mediated phosphate and vitamin D homeostasis in humans.     

Comparison of grey matter atrophy between patients with neuromyelitis optica and multiple sclerosis: a voxel-based morphometry study

Purpose

Previous studies have established regional grey matter (GM) loss in multiple sclerosis (MS). However, whether there is any regional GM atrophy in neuromyelitis optica (NMO) and the difference between NMO and MS is unclear. The present study addresses this issue by voxel-based morphometry (VBM).

Methods

Conventional magnetic resonance imaging (MRI) and T1-weighted three-dimensional MRI were obtained from 26 NMO patients, 26 relapsing–remitting MS (RRMS) patients, and 26 normal controls. An analysis of covariance model assessed with cluster size inference was used to compare GM volume among three groups. The correlations of GM volume changes with disease duration, expanded disability status scale (EDSS) and brain T2 lesion volume (LV) were analyzed.

Results

GM atrophy was found in NMO patients in several regions of frontal, temporal, parietal lobes and insula (uncorrected, p < 0.001). While extensive GM atrophy was found in RRMS patients, including most cortical regions and the deep grey matter (corrected for multiple comparisons, p < 0.01). Compared with NMO, those with RRMS had significant GM loss in bilateral thalami, caudate, left parahippocampal gyrus, right hippocampus and insula (corrected, p < 0.01). In RRMS group, regional GM loss in right caudate and bilateral thalami were strongly correlated with brain T2LV.

Conclusions

Our study found the difference of GM atrophy between NMO and RRMS patients mainly in deep grey matter. The correlational results suggested axonal degeneration from lesions on T2WI may be a key pathogenesis of atrophy in deep grey matter in RRMS.