Pandemic influenza is a strong motivator for participation in vaccine clinical trials among HIV-positive Canadian adults

BACKGROUND:

HIV-positive patients represent an immunosuppressed population at risk for severe influenza. In the event of a pandemic, such as 2009 H1N1, rapid implementation of vaccine clinical trials in target populations will be critical. In the present paper, knowledge and attitudes of HIV-positive adults regarding seasonal/pandemic influenza vaccination were evaluated, and facilitators and barriers to participation in vaccine clinical trials were explored.

METHODS:

A validated, 70-item, self-administered questionnaire was distributed to all HIV patients presenting for routine follow-up at eight Canadian Institutes of Health Research Canadian HIV Trials Network (CTN) sites from October 2008 to February 2009, as well as all participants in CTN trial 237. This study has representation from all Canadian provinces.

RESULTS:

In total, 610 HIV-positive adults responded (298 CTN 237 participants; 312 non-CTN 237 participants). Most reported receiving influenza vaccine last season (83% of CTN 237 participants versus 83% non-CTN 237 participants; P not significant) and most would receive a pandemic influenza vaccine if offered (76% versus 73%; P not significant). A majority believed that it was important to include HIV patients in vaccine clinical trials (65% versus 53%; P<0.001) and would agree to participate in trials of a pandemic vaccine if invited (86% versus 51%; P≤0.0001). Predictors of willingness to participate in a pandemic vaccine trial were ‘desire to be protected from pandemic flu’, OR 4.5 (95% CI 2 to 8) and ‘desire to help others’, OR 2.3 (95% CI 1.3 to 4.5). ‘Fear of needles’, OR 0.49 (95% CI 0.1 to 1.5) and ‘need for extra blood tests’, OR 0.49 (95% CI 0.2 to 1.4) were key barriers to participation.

CONCLUSION:

Most HIV-positive Canadian adults surveyed receive influenza vaccination. Protection from pandemic influenza is considered important and is a motivator for receiving influenza vaccine and future trial participation. Modifiable barriers to these objectives identified in the present study should be the focus of efforts to increase influenza immunization in this population.     

Frequent deletion of p16INK4a/MTS1 and p15INK4b/MTS2 in pediatric acute lymphoblastic leukemia

The tandemly linked p16INK4aMTS1 and p15INK4b/MTS2 genes on chromosome 9, band p21 encode proteins that function as specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6. This locus undergoes frequent bi-allelic deletion in human cancer cell lines, suggesting that the encoded proteins may function as tumor suppressors. However, more recent analysis of primary tumor samples has shown a much lower frequency of abnormalities affecting this region, raising doubt over the importance of these proteins in human malignancies. Hemizygous deletions and rearrangements of chromosome 9, band p21, are among the most frequent cytogenetic abnormalities detected in pediatric acute lymphoblastic leukemia (ALL), occurring in approximately 10% of cases. To determine if the p16INK4a/p15INK4b locus might be the target of these chromosomal lesions, we analyzed both genes in primary clinical samples from 43 pediatric ALL patients using interphase fluorescence in situ hybridization, Southern blot analysis, and the polymerase chain reaction. Deletions of p16INK4a/p15INK4b were identified in 18 of 20 cases with cytogenetically observed abnormalities of 9p and 5 of 23 with apparently normal chromosomes 9p, with the majority containing bi- allelic deletions (16 homozygous/7 hemizygous). Although most homozygous deletions involved both genes, Southern blot analysis showed an interstitial deletion in a single case that was confined to p16INK4a, suggesting that p15INK4b was not the critical target gene in this case. Sequence analysis of both p16INK4a and p15INK4b in all seven cases with hemizygous deletions failed to show mutations within the coding regions of the retained alleles. In this select group of patients, deletion of p16INK4a/p15INK4b was associated with T-cell phenotype, nonhyperdiploid karyotype (< 50 chromosomes), and poor event- free survival. These findings indicate that deletion of the p16INK4a/p15INK4b locus is one of the most common genetic abnormalities so far detected in pediatric ALL, and that loss of one or more of these cell cycle kinase inhibitors is important in leukemogenesis.     

牙本质小管封闭治疗牙本质过敏症的机制和效果

牙本质过敏症是由于釉质的完整性受到破坏,造成牙本质小管暴露,从而使牙齿对温度、化学物质和机械刺激等因素敏感的一种临床病症。其治疗的主要方法是封闭暴露的牙本质小管,降低牙本质小管的通透性。封闭方法按机制可分为原位沉积法、氟诱导矿化法、纳米粒子填塞法、粘接覆盖法和激光熔融法等。对于这些封闭方法实验室常用的效果评价手段主要包括扫描电镜观察和牙本质渗透性检测。本文就近年来封闭牙本质小管不同方法的内在机制和效果作一综述。     

Inhibition of platelet adhesion to fibronectin, fibrinogen, and von Willebrand factor substrates by complex gangliosides

Gangliosides, which are complex glycosphingolipids containing sialic acid, are found in cell membranes and have been implicated in a variety of cell surface events including cellular adhesion. Complex gangliosides were observed to inhibit the adhesion of thrombin- activated platelets to substrates of fibronectin, von Willebrand factor, and fibrinogen. This adhesion, which is mediated by the glycoprotein IIb-IIIa complex, was differentially inhibited by gangliosides depending on the number of sialic acid residues present within the ganglioside. The observed order of effectiveness was GT1b greater than GD1a greater than GM1 greater than asialo-GM1. Another structurally related glycosphingolipid, globoside, exhibited little inhibitory activity. In contrast to the inhibition of platelet adhesion to von Willebrand factor mediated by the glycoprotein IIb-IIIa complex, gangliosides had no detectable effect on the ristocetin-dependent adhesion of platelets to von Willebrand factor mediated by glycoprotein Ib. These results suggest that the function of the glycoprotein IIb- IIIa complex may be modulated by gangliosides in a manner similar to that previously described for the closely related vitronectin receptor.     

Increased levels of circulating Epstein-Barr virus (EBV)-infected lymphocytes and decreased EBV nuclear antigen antibody responses are associated with the development of posttransplant lymphoproliferative disease in solid-organ transplant recipients

Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disease (PTLD) is an uncommon but potentially fatal complication of immunosuppression in solid-organ transplant recipients. A semiquantitative DNA polymerase chain reaction assay was developed to amplify a unique 269-bp region of the EBNA-1 gene in peripheral blood lymphocytes (PBL) using the primers described by Telenti et al (J Clin Microbiol 28:2187, 1990). Serial samples were studied from 23 transplant recipients, 12 of whom were diagnosed with PTLD. The majority of transplant recipients who were EBV seropositive at the time of transplant surgery and who did not develop PTLD (5 of 7, 71%) exhibited less than a 10-fold increase in the levels of EBV-infected PBL over the 0.1 to 5 EBV genomes/10(6) PBL observed in immunocompetent EBV seropositive controls. Transplant recipients who were seronegative at the time of transplantation and who underwent a primary EBV infection but did not develop PTLD exhibited a reduced capacity to control viremia because the levels of EBV-infected PBL were up to 400 times greater than the 1.0 to 50 EBV genomes/10(6) PBL observed in individuals undergoing acute infectious mononucleosis (Rocci et al: N Engl J Med 296:132, 1977). However, all transplant recipients who developed PTLD exhibited a marked elevation of EBV-infected PBL independent of their serologic state at the time of transplantation. Six of the 10 transplant recipients with PTLD exhibited > or = 300,000 EBV genomes/10(5) PBL, two exhibited 10,000 to 50,000 EBV-infected genomes/10(5) PBL, and one each exhibited 2,500 and 500 EBV genomes/10(5) PBL. However, the latter two samples were obtained 4 to 5 weeks after the diagnosis of PTLD and may reflect a decrease in viral load resulting from immunomodulation. Marked decreases in the levels of EBV nuclear antigen-1 (EBNA-1), EBNA-2, and EBNA-LP antibodies correlated with the increase in EBV-infected PBL. Hence, a quantitative difference in circulating EBV viral load and EBNA antibody levels is evident between transplant recipients with and without PTLD and may be useful as a noninvasive prognostic marker with which to monitor and/or predict the development of PTLD.     

Inhibition of murine erythroid colony formation in vitro by interferon gamma and correction by interferon receptor immunoadhesin

It has been previously reported that inhibition of human erythroid colony-forming units (CFU-E) in vitro by interleukin-1 (IL-1) is an indirect effect, occurring through the production of interferon gamma (IFN gamma). IFN gamma, in turn, inhibits CFU-E colony formation directly, and its inhibitory effect can be overcome by exposure to high concentrations of erythropoietin (EPO). To develop an in vitro animal model for investigating inhibition of erythropoiesis by IFN gamma, the effects of recombinant murine (rm) IFN gamma on highly purified CFU-E from the spleens of mice infected with the anemia strain of the Friend virus (FVA) were studied. rmIFN gamma inhibited CFU-E colony formation in a dose-dependent manner. This inhibition occurred with large (> or = 8 cell) colonies only; smaller colonies were not affected. The inhibitory effect was corrected to 72% of control by high EPO concentrations of 64 U/mL. Murine CFU-E were then cultured with rmIFN gamma in the presence of a soluble murine IFN gamma receptor fused to the hinge and Fc domains of the human IgG1 heavy chain (mIFN gamma R- IgG). Inhibition of CFU-E colony formation by rmIFN gamma (100 U/mL) was corrected by mIFN gamma R-IgG in a dose-dependent manner, with an approximate IC50 of 0.05 nmol/L, and complete or near complete correction at 0.5 nmol/L. Similarly, a human IFN gamma R-IgG greatly reduced the inhibitory effect of recombinant human IFN gamma on human CFU-E. These experiments provide an in vitro animal model for studying the inhibitory effects of IFN gamma on erythropoiesis and indicate that IFN gamma R-IgG may be a useful agent for reducing the toxicity of IFN gamma in vivo.     

精神紧张致咬合紊乱1例

<正>1临床资料患者,女性,16岁,高中二年级学生,特长画画。头痛不适3 d,晚餐后突然头向左侧倾斜后仰,下颌向左侧偏斜,头颈部活动及开闭口受限,颞下颌关节处持续性疼痛半小时来我院就诊。查体:神智清晰,营养中等,查体合作,心、肺、腹未见异常。专科检查:头向左侧倾斜后仰,下颌向左偏,颈部及下颌侧向运动障碍,触之左侧颈前区僵硬并有     

胸腺肽与干扰素联合治疗慢性乙型肝炎58例观察

目的 :观察胸腺肽与干扰素联合应用与单用干扰素治疗慢性乙肝的疗效对比。方法 :选择慢性乙肝 5 8例 ,胸腺肽与干扰素联合组 32例 ,干扰素组 2 6例 ,根据用药时间观察各化验指标。结果 :血清HBeAg/抗HBe转换率至治疗第 6个月 ,联合组达 5 0 % ,干扰素组达 30 .7% ,联合组疗效显著高于干扰素组(P <0 0 5 )。两组治疗中 ,联合组HBVDNA阴转率高于干扰素组 (P <0 .0 5 )。结论 :胸腺肽与干扰素联用具有协同作用 ,治疗慢性乙肝优于干扰素组。     

Hyaluronic acid: a unique topical vehicle for the localized delivery of drugs to the skin

Hyaluronic acid (HA) is a naturally occurring polyanionic, polysaccharide that consists of N-acetyl-D-glucosamine and beta-glucoronic acid. It is present in the intercellular matrix of most vertebrate connective tissues especially skin where it has a protective, structure stabilizing and shock-absorbing role. The unique viscoelastic nature of HA along with its biocompatibility and non-immunogenicity has led to its use in a number of clinical applications, which include: the supplementation of joint fluid in arthritis; as a surgical aid in eye surgery; and to facilitate the healing and regeneration of surgical wounds. More recently, HA has been investigated as a drug delivery agent for various routes of administration, including ophthalmic, nasal, pulmonary, parenteral and topical. In fact, regulatory approval in the USA, Canada and Europe was granted recently for 3% diclofenac in 2.5% HA gel, Solaraze, for the topical treatment of actinic keratoses, which is the third most common skin complaint in the USA. The gel is well tolerated, safe and efficacious and provides an attractive, cost-effective alternative to cryoablation, curettage or dermabrasion, or treatment with 5-fluorouracil. The purpose of this review is to describe briefly the physical, chemical and biological properties of HA together with some details of its medical and pharmaceutical uses with emphasis on this more recent topical application.     

Chronic encapsulated mediastinal abscess presenting with remote cutaneous fistulization 12 years after redo aortic valve replacement for prosthetic valve endocarditis

Chronic encapsulated mediastinal abscess is an unusual complication of previous open heart surgery. We report on the case of a 79 year old male who presented with epigastric fistulization of an encapsulated anterior mediastinal abscess 12 years after a redo aortic valve replacement for prosthetic valve endocarditis. The encapsulated abscess and its complex branching tracts and the cutaneous fistula were excised completely except the thin longitudinal strip of the ascending aorta which formed part of the posterior wall of the infected tract. This was covered with transposed greater omentum based on right gastroepiploic artery pedicle. Patient remains fit and well 2 years after his operation.