Accuracy of supplementary serologic testing for human T-lymphotropic virus types I and II in US blood donors. Retrovirus Epidemiology Donor Study

Blood donations in the United States have been screened for antibody to human T-lymphotropic virus type I (HTLV-I) by HTLV-I enzyme immunoassay (EIA) since November 1988. Specimens repeatedly found to be reactive by EIA undergo confirmation by supplementary serologic tests. We assessed the accuracy of blood center testing of 994 HTLV-I EIA repeat-reactive specimens in five US blood centers between November 1988 and December 1991. Of 410 confirmed HTLV-I/II donations, 407 (99.3%) were infected with HTLV-I/II, as determined by polymerase chain reaction (PCR) (403 cases) and by repeat serologic testing (4 cases). The three false- positive results occurred in the first year of testing. Of 425 HTLV- indeterminate specimens, 6 (1.4%) were found to be infected by PCR (5 with HTLV-II and 1 with HTLV-I). None of 159 confirmatory test-negative donations was PCR positive. Of HTLV-I/II-seropositive specimens, 80.2% to 95.4% could be typed as HTLV-I or HTLV-II by type-specific serologic assays. These results support recommendations that HTLV-I/II- seropositive donors should be advised that they are infected with HTLV- I, HTLV-II, or HTLV-I/II (depending on results of type-specific assays). HTLV-indeterminate donors should be advised that their results only rarely indicate HTLV infection. HTLV confirmatory test-negative donors should be reassured that they are not infected with HTLV-I or HTLV-II.     

诱导化疗在局部晚期头颈癌中的作用

作为标准化的非手术治疗,诱导化疗(ICT)在治疗局部晚期头颈鳞癌已有几十年的历史,但是关于其作用尚存争议。同期放化疗(CRT)是目前标准化的非手术治疗,然而由于ICT能够使肿瘤体积缩小,提高放疗的可行性,改善患者对放疗的耐受力,增加放疗后器官功能保留的可能性及降低远处转移率。所以,对ICT的研究从未停止。该文对近期随机试验进行回顾分析,与手术或单独CRT比较,评估ICT中紫杉醇的价值。Meta分析比较ICT中紫杉醇和顺铂及5氟尿嘧啶的作用。之前的随机试验中,并没有ICT提高生存率的报道。但     

The first case of locally acquired tick-borne Babesia microti infection in Canada

A child with a complicated medical history that included asplenia acquired an infection with Babesia microti in the summer of 2013 and had not travelled outside of Manitoba. Although the clinical findings were subtle, astute laboratory work helped to reach a preliminary identification of Babesia species, while reference laboratory testing confirmed the diagnosis. Blacklegged ticks (Ixodes scapularis) are known to transmit Borrelia burgdorferi and Anaplasma phagocytophilum in the province; however, the present case represents the first known instance of tick-borne B microti, both in Manitoba and in Canada. The expanding territory of the blacklegged tick increases the relevance of this emerging infection. Clinicians, laboratory medical practitioners and public health officials should be aware of B microti as a potential locally acquired infection in Canada.     

The impact of periodontitis on oral health‐related quality of life: a review of the evidence from observational studies

Modern population based oral health management requires a complete understanding of the impact of disease in order to provide efficient and effective oral health care and guidance. Periodontitis is an important cause of tooth loss and has been shown to be associated with a number of systemic conditions. The impact of oral conditions and disorders on quality of life has been extensively studied. However, the impact of periodontitis on quality of life has received less attention. This review summarizes the literature on the impact of periodontitis on oral health‐related quality of life (OHRQoL). Relevant publications were identified after searching the MEDLINE and EMBASE electronic databases. Screening of titles and abstracts and data extraction was conducted. Only observational studies were included in this review. Most of the reviewed studies reported a negative impact of periodontitis on OHRQoL. However, the reporting standards varied across studies. Moreover, most of the studies were conducted in developed countries.     

Estrogen induces premature luteal regression in rhesus monkeys during spontaneous menstrual cycles, but not in cycles driven by exogenous gonadotropin-releasing hormone

Administration of exogenous estradiol during the mid- to late luteal phase of the menstrual cycle results in premature regression of the corpus luteum. The present study was initiated to identify the site of action of estrogen as well as to determine why administration of estrogen during the early luteal phase of the menstrual cycle does not result in luteolysis. Based upon extant literature, we hypothesized that estrogen and progesterone synergize to promote premature luteal regression. We tested this hypothesis in intact, spontaneously cycling rhesus monkeys by inserting estradiol, progesterone, or estrogen plus progesterone capsules on days 2 through 6 of the luteal phase. Insertion of estrogen or progesterone capsules alone did not advance luteolysis compared with the effect of control empty implants (n = 3). In contrast, insertion of estrogen plus progesterone implants on days 2 through 6 of the luteal phase resulted in a significant lowering of serum progesterone concentrations, and menses was advanced 5-6 days compared with control cycles. On the basis of these findings in spontaneously cycling monkeys, we speculated that estrogen treatment causes luteal regression only in the presence of a progesterone-mediated decrease in LH pulse frequency. To test this hypothesis, we used rhesus monkeys whose endogenous gonadotropin secretion was abolished by either placement of radiofrequency lesions in the mediobasal hypothalamus or transection of the hypothalamic-pituitary stalk. Ovulatory menstrual cycles were restored by pulsatile administration of exogenous synthetic GnRH. Insertion of estradiol capsules during the luteal phase into animals whose gonadotropin pulse frequency was set at either one pulse per h or one pulse per 8 h failed to cause premature luteal regression (n = 4). These findings indicate that whereas estrogen promotes luteal regression in intact, spontaneous cycling rhesus monkeys, it does not do so in animals whose gonadotropin secretion is controlled by exogenous GnRH. On the basis of these observations, we conclude that the hypothalamus is a major site of action of estrogen in the initiation of luteal regression in macaques.     

Regulation of interleukin-12 expression in human monocytes: selective priming by interferon-gamma of lipopolysaccharide-inducible p35 and p40 genes

Interleukin-12 (IL-12) is a monocyte/macrophage-derived cytokine that is critical for T lymphocyte and natural killer cell activities and functions. In this study, we examined the regulation of IL-12 expression by human monocytes in response to bacterial lipopolysaccharide (LPS). Several novel aspects of IL-12 induction from monocytes were shown. Optimal expression of IL-12 mRNA and bioactivity required specific priming of monocytes by interferon-gamma (IFN-gamma) before LPS stimulation. Granulocyte-macrophage colony-stimulating factor (GM-CSF) provided an equivalent priming stimulus for LPS-induced tumor necrosis factor (TNF) and IL-12 p40 mRNA, but primed poorly for LPS-inducible p35 message and secreted IL-12 activity. Macrophage colony-stimulating factor (M-CSF), although a potent survival factor for monocytes, showed no priming activity for IL-12 production. Time course experiments demonstrated independent regulation of p40 and p35 by IFN-gamma and LPS. LPS inducibility of p40 expression required only a brief exposure to IFN-gamma (2 hours), while prolonged exposure (+/- 24 hours) to IFN-gamma resulted in diminishing levels of p40 mRNA. p35 inducibility (by LPS) required a longer exposure to IFN-gamma (8 to 16 hours), and continued to be inducible up to 40 hours following IFN- gamma priming. Both mRNAs were rapidly induced (1 to 2 hours) in IFN- gamma-primed monocytes; p35 message reached a plateau by 2 hours, while p40 continued to accumulate. Finally, both p40 and p35 were directly induced by LPS in the presence of cycloheximide. These results indicated that both p40 and p35 are LPS-inducible in monocytes following IFN-gamma pretreatment, and that the regulated expression of p35 controls the level of active IL-12 protein in purified human monocytes. The selectivity of priming by IFN-gamma is in accord with a putative role for IL-12 in the initiation and amplification of TH1-type responses.     

Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2

Human T-cell lymphotropic virus I (HTLV-I)-induced adult T-cell leukemia (ATL) cells constitutively express interleukin-2 (IL-2) receptors identified by the anti-Tac monoclonal antibody (MoAb), whereas normal resting cells do not. This observation provided the scientific basis for a trial of intravenous anti-Tac in the treatment of nine patients with ATL. The patients did not suffer untoward reactions and did not have a reduction in the normal formed elements of the blood, and only one of the nine produced antibodies to the anti-Tac MoAb. Three patients had transient mixed, partial, or complete remissions lasting from 1 to more than 8 months after anti-Tac therapy, as assessed by routine hematologic tests, immunofluorescence analysis of circulating cells, and molecular genetic analysis of HTLV-I provirus integration and of the T-cell receptor gene rearrangement. The precise mechanism of the antitumor effects is unclear; however, the use of a MoAb that prevents the interaction of IL-2 with its receptor on ATL cells provides a rational approach for the treatment of this malignancy.     

冠状动脉粥样硬化ADAMTS7新位点的发现和冠状动脉粥样硬化中ABO位点与心肌梗死的相关性:两项全基因组关联研究

<正>背景:该研究旨在评价在现有的冠状动脉粥样硬化的病变中,遗传因素对粥样硬化斑块进展及特异性心肌梗死是否存在显著作用。方法:对欧洲后裔参与者冠状动脉造影表型进行了两项全基因组关联研究(GWAS),为寻找冠状动脉疾病(CAD)易感性基因位点,研究比较了有异常(n=12393)和无异常的(对照组n=7383)个体;为寻找心肌梗死易感性基因位点,也同时比较了造影证实存在CAD并且有心肌梗死的个体(n=5783)与虽有CAD但无心肌梗死的个体(n=3644)。