Fatal meningoencephalitis due to Bacillus anthracis

Abstract: We report the first case of fatal anthrax meningoencephalitis in Hong Kong over the past 60 years. A 13 year-old boy presented with right lower quadrant pain, diarrhoea and progressive headache. Lumbar puncture yielded gram positive bacilli initially thought to be Bacillus cereus, a contaminant. He was treated with ampicillin and cefotaxime, but died 3 days after hospitalization. The organism isolated from blood and cerebrospinal fluid was later identified as Bacillus anthracis.     

经桡动脉冠状动脉介入治疗中5F与6F导引导管的对比研究

目的比较5French(5F)及6French(6F)导引导管在经桡动脉冠状动脉介入治疗(TRI)患者中的安全性及有效性。方法共纳入2009年2月至2010年3月患者,收集相关资料录入数据库,包括患者基线临床资料、导引导管的尺寸、靶血管、靶病变的特点、手术的成功率、手术失败原因、经桡动脉冠状动脉介入治疗手术的成功率及失败原因、患者住院期间主要不良心血管事件率及术后桡动脉闭塞率。结果连续纳入患者共185例,接受195次经桡动脉冠状动脉介入治疗术,平均年龄(57±11)岁(33～81岁);其中54例患者纳入6F导引导管组,共进行56次手术,治疗89处病变;138例患者纳入5F导引导管组,共行146次手术,治疗231处病变。AHA B2/C型病变比例在两组间差异无统计学意义(5F组43.7%/29.0%比6F组46.1%/34.6%,P>0.05),但慢性闭塞性病变、分叉病变、钙化病变5F组显著少于6F组(5.6%比14.6%,P=0.005;23.4%比37.1%,P=0.012;9.5%比47.2%,P<0.001);组间的手术时间[(45±21)min比(46±19)min)]、手术X线曝光时间[(15±12)min比(16±13)min]、使用造影剂量[(140±45)ml比(156±56)ml]差异均无显著统计学意义(P>0.05),但是5F组造影剂用量有减少的趋势(P=0.066);组间住院时间[(1.40±1.26)d比(1.29±0.69)d]和手术成功率(95.2%比94.6%)也差异无统计学意义(P>0.05);5F组1例患者术后桡动脉闭塞,6F组无患者术后桡动脉闭塞(P=1.0),5F组1例发生卒中。结论经桡动脉冠状动脉介入治疗,即使是复杂及高危冠脉病变,5F导引导管有效、安全,手术成功率不低于常规使用的6F导引导管;换用5F导引导管进行冠状动脉介入治疗是一种有吸引力的选择。     

The CD11b promoter directs high-level expression of reporter genes in macrophages in transgenic mice [published erratum appears in Blood 1995 Apr 1;85(7):1983]

CD11b is the alpha chain of the Mac-1 integrin and is preferentially expressed in myeloid cells (neutrophils, monocytes, and macrophages). We have previously shown that the CD11b promoter directs cell-type- specific expression in myeloid lines using transient transfection assays. To confirm that these promoter sequences contain the proper regulatory elements for correct myeloid expression of CD11b in vivo, we have used the -1.7-kb human CD11b promoter to direct reporter gene expression in transgenic mice. Stable founder lines were generated with two different reporter genes, a Thy 1.1 surface marker and the Escherichia coli lacZ (beta-galactosidase) gene. Analysis of founders generated with each reporter demonstrated that the CD11b promoter was capable of driving high levels of transgene expression in murine macrophages for the lifetime of the animals. Similar to the endogenous gene, transgene expression was preferentially found in mature monocytes, macrophages, and neutrophils and not in myeloid precursors. These experiments indicate that the -1.7 CD11b promoter contains the regulatory elements sufficient for high-level macrophage expression. This promoter should be useful for targeting heterologous gene expression to mature myeloid cells.     

Interleukin-2 induction of lymphokine-activated killer (LAK) activity in the peripheral blood and bone marrow of acute leukemia patients: II. Feasibility of LAK generation in children with active disease and in remission

Activation and expansion in culture with rIL-2 of peripheral blood (PB) and/or bone marrow (BM) specimens derived from children with ALL and ANLL, with active disease (AP) and in remission were studied (RP). Baseline NK cytolytic activity from AP was found to be depressed, whereas RP-derived cells had normal NK activity, as assayed against K562 targets. Culture in rIL-2 significantly enhanced the NK activity of both AP- and RP-derived cells and generated LAK activity, as assayed by 4-hour 51Cr release, against NK-resistant Raji cell line and against fresh, allogeneic, and autologous tumor cells. Lytic activity against fresh, cryopreserved leukemia blasts was of lower than that found against cell lines. In three patients higher lytic activity against autologous than against allogeneic blasts was demonstrated. Expansion in culture with rIL-2 varied from twofold to 120-fold. rIL-2 activation and expansion was better in RP than in AP. The predominant phenotype of activated cells, as determined by flow cytometry, was [mean % (SD)]: CD3- = 54 (12), CD8+ = 55 (17), and NKH1+ = 26 (7). The consistently high level of CD8+ cells was accompanied by very low levels of CD4+ cells: mean = 11% (14). Double-marker analysis showed mean of 33% (10) for CD3+/NKH1+ cells and mean = 32 (11) for CD8+/NKH1+ cells, implying that these populations were overlapping. Kinetics of expression of cell surface markers during 2 to 3 weeks in culture showed that CD8+ and NKH1+ enrichment occurred during the first week and lasted for up to 4 weeks, whereas CD4+ expression decreased after the second week. A significant decrease in the expression of IL-2 receptors (CD25) was observed from the second week of culture. This study shows the feasibility of in vitro generation of killer cells from PB and BM of pediatric leukemia patients.     

The receptor for urokinase-type plasminogen activator and urokinase is translocated from two distinct intracellular compartments to the plasma membrane on stimulation of human neutrophils

The cellular receptor for urokinase-type plasminogen activator (uPAR) binds pro-urokinase (pro-uPA) and facilitates its conversion to enzymatically active urokinase (uPA). uPA in turn activates surface- bound plasminogen to plasmin, a process of presumed importance for a number of biologic processes including cell migration and resolution of thrombi. We have previously shown that uPAR is expressed on the plasma membrane of circulating neutrophils, and we now report that stimulation with phorbol myristate acetate (PMA), FMLP, or tumor necrosis factor- alpha results in a rapid increase in the expression of uPAR. This process is accompanied by an increased cell-associated plasminogen activation after preincubation of neutrophils with pro-uPA in vitro. By subcellular fractionation of unstimulated neutrophils, 50% of uPAR is recovered in fractions containing latent alkaline phosphatase, corresponding to an intracellular compartment of easily mobilizable secretory vesicles distinct from both primary and specific granules, whereas the remaining 50% of uPAR is associated with a compartment eluting close to the specific granules. In contrast, the ligand pro-uPA is primarily (approximately 80%) found in the specific granules, but small amounts of pro-uPA/uPA (approximately 20%) coelute with latent alkaline phosphatase. Stimulation of neutrophils with FMLP results in translocation of uPAR as well as of pro-uPA from the secretory vesicles, whereas stimulation with PMA is required to translocate material from specific granules. Flow cytometry of neutrophils saturated with exogenous diisopropyl fluorophosphate-uPA shows a large excess (approximately 90%) of unoccupied uPAR on resting as well as FMLP- and PMA-stimulated neutrophils, suggesting a possible role for exogenous pro-uPA in providing neutrophils with a potential for plasminogen activation. These processes may be important for neutrophil extravasation and migration through extracellular matrix and for the contribution of neutrophils to resolution of thrombi.     

Associations of loneliness and social isolation with actigraph and self-reported sleep quality in a national sample of older adults

Study ObjectivesTo examine associations of social isolation and loneliness with sleep in older adults and whether associations differ for survey and actigraph sleep measures.MethodsThis study used data from the National Social Life, Health, and Aging Project (NSHAP), a nationally representative study of community-dwelling older adults born 1920–1947. A random one-third of participants in 2010–2011 were invited to participate in a sleep study (N = 759) that included survey questions, 72 hours of wrist actigraphy, and a sleep log. Perceived loneliness was measured using three questions from the UCLA Loneliness Scale. An index of social isolation was constructed from nine items that queried social network characteristics and social interactions. We used ordinary least squares and ordinal logistic regression to examine whether sleep measures were associated with loneliness and social isolation adjusted for potential sociodemographic confounders.ResultsSocial isolation and loneliness had a low correlation (Spearman’s correlation = 0.20). Both loneliness and social isolation were associated with actigraphy measures of more disrupted sleep: wake after sleep onset and percent sleep. Neither was associated with actigraph total sleep time. Increased loneliness was strongly associated with more insomnia symptoms and with shorter sleep duration assessed by a single question, but social isolation was not. More isolated individuals spent a longer time in bed.ConclusionsWe found that both loneliness and social isolation were associated with worse actigraph sleep quality, but their associations with self-reported sleep differed. Only loneliness was associated with worse and shorter self-reported sleep.     

Prostate cancer detection upon transrectal ultrasound-guided biopsy in relation to digital rectal examination and prostate-specific antigen level: what to expect in the Chinese population?

We investigated the prostate cancer detection rates upon transrectal ultrasound (TRUS)-guided biopsy in relation to digital rectal examination (DRE) and prostate-specific antigen (PSA), and risk factors of prostate cancer detection in the Chinese population. Data from all consecutive Chinese men who underwent first TRUS-guided prostate biopsy from year 2000 to 2013 was retrieved from our database. The prostate cancer detection rates with reference to DRE finding and PSA level of < 4, 4–10, 10.1–20, 20.1–50 and > 50 ng ml⁻¹ were investigated. Multivariate logistic regression analyses were performed to investigate for potential risk factors of prostate cancer detection. A total of 2606 Chinese men were included. In patients with normal DRE, the cancer detection rates were 8.6%, 13.4%, 21.8%, 41.7% and 85.2% in patients with PSA < 4, 4–10, 10.1–20, 20.1–50 and > 50 ng ml⁻¹ respectively. In patients with abnormal DRE, the cancer detection rates were 12.4%, 30.2%, 52.7%, 80.6% and 96.4% in patients with PSA < 4, 4–10, 10.1–20, 20.1–50 and > 50 ng ml⁻¹ respectively. Older age, smaller prostate volume, larger number of biopsy cores, presence of abnormal DRE finding and higher PSA level were associated with increased risk of prostate cancer detection upon multivariate logistic regression analyses (P < 0.001). Chinese men appeared to have lower prostate cancer detection rates when compared to the Western population. Taking the different risk factors into account, an individualized approach to the decision of TRUS-guided biopsy can be adopted.     

Intra-individual daily and yearly variability in actigraphically recorded sleep measures: the CARDIA study

STUDY OBJECTIVES: To describe the day-to-day and year-to-year variation in sleep characteristics among early middle-aged adults. DESIGN: Participants wore an Actiwatch (Mini Mitter, Inc) for 3 days on two occasions approximately 1 year apart. PARTICIPANTS: N = 669 participants aged 38-50 years from the Chicago site of the Coronary Artery Risk Development in Young Adults (CARDIA) cohort study. MEASUREMENTS AND RESULTS: Sleep measures included sleep duration, sleep latency, sleep efficiency, and time in bed. For each sleep parameter, total variance was decomposed into between-subject variance, within-subject variance from day to day, and within-subject variance from year to year. The standard deviation was calculated from the variance. Analysis yielded a within-subject daily standard deviation (SD) of 1.26 hours and a within-subject yearly SD of 0.39 hours for sleep duration. Daily SD was 30.7 minutes and yearly SD was 6.3 minutes for within-subject variability of sleep latency. Daily SD was 8.4% and yearly SD was 2.7% for within-subject variability of sleep efficiency. Finally, daily SD was 1.31 hours and yearly SD was 0.52 hours for within-subject variability of time in bed. CONCLUSIONS: For each of the 4 sleep characteristics, nightly variability was much greater than yearly variability, meaning sleep behavior changes little in one year in this cohort of early middle-aged adults, despite large daily fluctuations. These results have important methodological implications, including that single-day measures of sleep may not accurately reflect habitual behavior.     

Interleukin 2 induction of lymphokine-activated killer (LAK) activity in the peripheral blood and bone marrow of acute leukemia patients. I. Feasibility of LAK generation in adult patients with active disease and in remission

The feasibility of in vitro interleukin 2 (IL-2) activation and expansion of mononuclear cells (MNCs) derived from adult patients with acute myelogenous leukemia (ANLL) was studied. Patients' natural killer (NK) and lymphokine-activated killer (LAK) cell activity was compared with that of normal donors in terms of: (a) cytolytic activity (four- hour 51Cr release assay) against an NK-sensitive target (K562), NK- resistant targets (Raji/Daudi), and fresh/cryopreserved autologous and allogeneic leukemic blasts; (b) proliferation and expansion in culture with 1,000 U/mL recombinant IL 2 (rIL 2); and (c) the cell surface phenotype of the cultured cells. In 21 of 24 patients with active disease (AP) MNCs derived from the peripheral blood (PBL) or bone marrow (BM) could be cultured and expanded in the presence of rIL 2. These cultures initially contained between 30% and 50% blasts, and during 2 to 4 weeks of culture destruction of blasts and enrichment of up to 60% in cells with the morphology of large granular lymphocytes (LGLs) was observed. Expansion in culture varied between two- and 100- fold. MNCs from all patients in remission (RP) could be activated by rIL 2 and expanded up to 30-fold after 1 to 3 weeks in culture. NK activity of fresh PBLs from AP was significantly lower than in normal controls, whereas NK activity of RP was within the normal range. High levels of postactivation NK and LAK activity on K562/Raji/Daudi and on fresh/cryopreserved leukemic blasts was generated in approximately 50% of cases of AP and in most RP. Cell surface phenotype studies showed that cultured cells derived from ANLL patients were significantly enriched (up to 40%) in NKH-1 (Leu 19) positive cells, with RP LAK cells also expressing a high proportion of CD16 positive cells (up to 40%). This study has shown that it is feasible to activate and significantly expand killer cells derived from active disease and remission ANLL patients during 1 to 3 weeks culture with IL 2 with good maintenance of cytolytic activity. Both initial NK activity and LAK generation was optimal in remission patients. Based on data from this study, a clinical protocol has been developed for treatment of early relapse ANLL patients with LAK cells cultured for 1 to 3 weeks and systemic IL 2.