Quantile regression for the statistical analysis of immunological data with many non-detects

Background

Hemolytic uremic syndrome (HUS) leading to acute kidney failure, is a condition linked to the production of primarily Shiga toxin 2 (Stx2) by some E. coli serotypes. We have previously shown that Stx2 A subunit-specific human monoclonal antibody (HuMAb) 5C12, and B subunit-specific HuMAb 5H8 inhibit cultured cell death, and protect mice and piglets from fatal Stx2-intoxication. We have also shown that 5H8 blocks binding of Stx2 to its cell-surface receptor globotriaosyl ceramide (Gb₃), whereas Stx2 when complexed with 5C12 binds Gb₃ with higher affinity than Stx2. The mechanism by which 5C12 neutralizes Stx2 in vitro involves trapping of Stx2 in the recycling endosomes and releasing it into the extracellular environment. Because of the clinical implications associated with the formation of Stx2/antibody complexes and the potential for trapping and clearance through a severely damaged kidney associated with HUS, we investigated the likely site(s) of Stx2/antibody localization and clearance in intoxicated mice treated with antibody or placebo.

Results

Mice were injected with radiolabeled Stx2 (¹²⁵I-Stx2) 4 hours after administration of 5C12, 5H8, or phosphate buffered saline (PBS) and the sites of localization of labeled Stx2, were investigated 3, 24 and 48 hours later. The liver recorded statistically much higher concentrations of labeled Stx2 for groups receiving 5C12 and 5H8 antibodies after 3, 24 and 48?hours, as compared with the PBS group. In contrast, highest levels of labeled Stx2 were detected in the kidneys of the PBS group at all 3 sampling times. Mice receiving either of the two HuMAbs were fully protected against the lethal effect of Stx2, as compared with the fatal outcome of the control group.

Conclusions

The results suggest that HuMAbs 5C12 and 5H8 promoted hepatic accumulation and presumably clearance of toxin/antibody complexes, significantly diverting Stx2 localization in the kidneys, the target of Stx2 and the cause of HUS. This is in contrast to the fatal outcome of the control group receiving PBS. The results also confirm earlier observations that both HuMAbs are highly and equally protective against Stx2 intoxication in mice.     

Oral squamous cell carcinoma: review of prognostic and predictive factors

Oral squamous cell carcinoma has a remarkable incidence worldwide and a fairly onerous prognosis, encouraging further research on factors that might modify disease outcome. In this review article, the authors approach the factors that may exert influence on the prognosis and eventually guide the selection of patients for more aggressive therapies. Published scientific data was collected, selected, and grouped into 3 main clusters: patient-, tumor-, and treatment-related factors. Well established aspects are discussed, but also those less common or with only supposed usefulness. Disease staging, extracapsular dissemination, resection margin free of disease, and tumor thickness are factors with high influence on the prognosis. There has been an increasing interest in the study of tumor molecular factors, and some have been strongly correlated with the outcome, showing promising pathways for the future development of more effective prognosis systems and anticancer therapies.     

The strategic management: the methodology applied by the "Centre Hospitalier Regional Universitaire"

This work is a general presentation of the "Démarche Stratégique", a strategic process applied by the "Centre Hospitalier Régional Universitaire" (CHRU) at Lille, France. The hospital management methodology relies on the strategic analysis of the best alternatives for rationalizing the hospital mission. It takes into account a competitive environment, in which it is necessary to structure health care networks based on the negotiation of inpatient care goals. The author presents the phases and main methodological tools of the approach, as well as a preliminary evaluation of its potentials.     

三维超声心动图测定机械瓣瓣口面积初步经验

观察三维超声心动图测定机械瓣瓣口面积的可行性。方法１１例机械瓣置换病例,用任意 切面（ａｎｙｐｌａｎｅ）３ＤＥ测定机械瓣瓣口有效面积,将测定值与多普勒超声心动图（ＤＥ）测定的有效瓣口面积（包括实测值和文献报道测值）及生产厂商提供的离体瓣口面积比较。     

Impairment of breast cancer cell invasion by COX-2-specific inhibitor NS398: roles of CXCR4 and of uPA system

Inhibition of cyclooxygenase-2 (COX-2) is known to impair cancer cell metastatic behaviour, but the mechanisms involved largely remain elusive. We aimed to analyse whether the antimetastatic effect of COX-2 inhibition in breast cancer cells could be explained by variations in the expression levels of chemokine receptor CXCR4, vascular endothelium growth factor (VEGF) and UPA/UPAR components of the urokinase plasminogen activator system (uPAR). Breast cancer cell line MDA-MB-231 was exposed to COX-2-specific inhibitor NS398. Experimental data were assessed using Matrigel invasion tests, qRT-PCR, ELISA, flow cytometry and MTT test. Exposure to NS398 had no major effect on cell viability, apoptosis or VEGF production. Cell invasion was significantly decreased with reductions ranging from of 3.6% with 10???M NS398 to 81.04% with 100???M NS398. CXCR4 membrane expression was significantly reduced by 18% (P?<?0.05) when cells were treated with 100???M of NS398 for 72?h. UPA mRNA levels were significantly reduced to 78 and 63% after treatment with 10???M NS398 for 48 and 72?h, respectively (P?<?0.05). UPAR mRNA levels also decreased with mild NS398 concentrations, reaching the lowest level of 56% with 50???M of NS398 for 48?h (P?<?0.05). With NS398 higher concentrations, UPAR and UPA expression levels increased. According to our results, impairment of expression of CXCR4, UPA and UPAR differentially contribute to the antimetastatic effect of COX-2 inhibitors depending on drug concentration.     

Prevalence and classification of HIV-associated oral lesions

OBJECTIVES: An International Workshop addressed the prevalence and classification of HIV/AIDS associated oral lesions.
DESIGN: Five questions provided the framework for discussion and literature review. What is the prevalence of oral lesions in children and adults? Should the accepted classification of HIV-related oral lesions be modified in the light of recent findings? Why is there a gender difference in the prevalence of oral lesions in developed and developing countries? Are there unusual lesions present in developing countries? Is there any association between modes of transmission and the prevalence of oral lesions?
RESULTS: Workshop discussion emphasized the urgent need for assistance in the development of expertise to obtain accurate global prevalence data for HIV-associated oral lesions. Oral candidiasis has been consistently reported as the most prevalent HIV-associated oral lesion in all ages. Penicilliosis marneffei, a newly described fungal infection, has emerged in South-east Asia. Oral hairy leukoplakia and Kaposi's sarcoma appear to be associated with male gender and male-to-male HIV transmission risk behaviours. These lesions occur only rarely in children.
CONCLUSIONS: Additional prevalence data are needed from developing countries prior to substantially altering the 1993 ECC/WHO Classification of oral lesions associated with adult HIV infection. The workshop confirmed current oral disease diagnostic criteria.