The impact of a quadrivalent human papillomavirus (types 6, 11, 16, 18) virus-like particle vaccine in European women aged 16 to 24

Background  Quadrivalent human papillomavirus (HPV types 6/11/16/18) L1 VLP vaccine is highly effective in preventing HPV 6/11/16/18-related cervical and external genital disease. Herein, we evaluated the impact of the quadrivalent HPV 6/11/16/18 L1 VLP vaccine on prevention of HPV-associated cervico-genital lesions in a broad population of sexually active European women.
Methods  Female subjects ( N = 9265) aged 16–24 with four or fewer lifetime sexual partners were enrolled and randomized to quadrivalent HPV vaccine or placebo. Subjects underwent cervicovaginal sampling for HPV DNA detection. Papanicolaou testing and anti-HPV 6/11/16/18 serology testing was also performed.
Results  Vaccine efficacy against lesions representing immediate cervical cancer precursors (cervical intraepithelial neoplasia grade 2/3 or adenocarcinoma in situ ) related to HPV 6/11/16/18 in the per-protocol population was 100.0%[95% confidence interval (95% CI), 89.8–100.0]. Efficacy against external genital lesions (vulvar or vaginal intraepithelial neoplasia, condyloma, vulvar or vaginal cancer) related to vaccine HPV types in the per-protocol European population was 99.0% (95% CI, 94.4–100.0).
Conclusion  These data demonstrate that quadrivalent HPV 6/11/16/18 vaccination programs in 16- to 24-year-old European women can be beneficial.
NCT0009252, NCT00092534, NCT00092495     

Infection dynamics and virus-induced apoptosis in cell culture-based influenza vaccine production—Flow cytometry and mathematical modeling

Cell culture-based influenza vaccine manufacturing is of growing importance. Depending on virus strains, differences in infection dynamics, virus-induced apoptosis, cell lysis and virus yields are observed. Comparatively little is known concerning details of virus–host cell interaction on a cellular level and virus spreading in a population of cells in bioreactors. In this study, the infection of MDCK cells with different influenza A virus strains in lab-scale microcarrier culture was investigated by flow cytometry. Together with the infection status of cells, virus-induced apoptosis was monitored. A mathematical model has been formulated to describe changes in the concentration of uninfected and infected adherent cells, dynamics of virus particle release (infectious virions, hemagglutinin content), and the time course of the percentage composition of the cell population.     

Myocardial perfusion imaging with technetium-99m sestamibi SPECT in the evaluation of coronary artery disease

Technetium-99m hexakis-2-methoxy-isobutyl-isonitrile(^99mTc sestamibi) has been used for myocardial perfusion imaging in the evaluation of coronary artery disease (CAD) since 1990. The experience of its use in an Asian population with and without previous myocardial infarction (Ml), diabetes mellitus (DM), hypertension (HPT) and collateral circulation (COL) is reported. One hundred and thirty-nine patients who underwent treadmill exercise testing with ^99mTc sestamibi single photon emission computed tomography (SPECT) and coronary angiogram were studied. The overall sensitivity for the detection of CAD was 91.0% and specificity was 64.7%. For patients without previous myocardial infarction, the sensitivity was 83.8% and specificity was 83.3%. Patients with COL had a higher sensitivity while those with HPT had a lower specificity. Sensitivity was higher in patients with multi-vessel disease (MVD) than single vessel disease (SVD). The overall detection for individual artery stenosis was 74.1% with a specificity of 73.1 %. Amongst the three major coronary arteries, sensitivity was highest for the right coronary artery and specificity was highest for the left circumflex artery. Specificity was higher in patients without MI or COL. We found that the agreement between ^99mTc sestamibi SPECT and coronary angiogram for the extent of CAD was only 52.5%. The concordance rate was higher for patients with MVD than SVD. It is concluded that ^99mTc sestamibi SPECT is a sensitive and specific test for the detection of CAD and localization of disease to individual coronary arteries in our patients with some differences in the subgroups. Agreement between coronary angiogram and ^99mTc sestamibi for the extent of coronary artery disease was also satisfactory.     

Analgesia for shock wave lithotripsy

PURPOSE: We evaluated the effectiveness of and patient preference for analgesia used during shock wave lithotripsy by comparing diclofenac alone with a combination of diclofenac and patient controlled analgesia, that is alfentanil. MATERIALS AND METHODS: A total of 64 patients were treated using a Lithotriptor S (Dornier Medical Systems, Marietta, Georgia) and randomized to receive diclofenac alone or combined with an alfentanil patient controlled analgesia pump. If treated twice, they crossed over to the alternative form of analgesia. A record was maintained of the site and size of the stone, maximum power achieved, number of shocks, amount of alfentanil used and need for additional analgesia. After treatment patients scored on a visual analog scale the maximum level of pain and satisfaction with analgesia. RESULTS: There was no difference in the mean size of the stone treated (8.6 and 7.5 mm.), energy level (71% and 71% or approximately 17 kV.) or number of shocks (3,000 and 2,900, respectively) in the groups. Only 2 patients in the diclofenac group required additional analgesia and there were no significant side effects from either treatment. The mean pain scores were not significantly different in the diclofenac and patient controlled analgesia groups (3.54 and 2.93, respectively, (p = 0.34), although those on patient controlled analgesia were more satisfied (7.72 versus 9.14, p = 0.04). Of the 38 patients who presented twice 58% preferred diclofenac alone. CONCLUSIONS: This study suggests that there is no significant difference in the level of pain experienced with diclofenac alone or when combined with an alfentanil patient controlled analgesia pump during shock wave lithotripsy. However, patients are more satisfied with treatment when a patient controlled analgesia pump is available.     

Toxicokinetic of HEMA in guinea pigs

Objective. Unconverted 2-hydroxyethylmethacrylate (HEMA) can be released from dental resin materials and can enter the body in humans. In the present study the uptake, distribution and excretion of ¹⁴C-HEMA applied via different routes were examined in vivo in guinea pigs.

Methods. HEMA (0.02 mmol/kg bw labelled with a tracer dose ¹⁴C-HEMA 0.3 Bq/g bw) was administered by gastric tube or by subcutaneous injection. Urine, feces, and exhaled carbon dioxide were collected for 24 h after administration. Guinea pigs were killed 24 h after the beginning of the experiment and various organs removed and ¹⁴C radioactivity measured.

Results. Low fecal ¹⁴C levels (about 2% of the dose) and urinary levels of about 15% after 24 h were noted with either route of administration. Direct measurement of exhaled CO₂ showed that about 70% of the dose left the body via the lungs. Two pathways for the metabolism of ¹⁴C-HEMA can be described. It is likely that ¹⁴C-pyruvate is formed in vivo resulting in the formation of toxic ¹⁴C-HEMA intermediates. ¹⁴C-HEMA was taken up rapidly from the stomach and small intestine after gastric administration and was widely distributed in the body following administration by each of the routes.

Conclusions. Clearance from most tissues following gastric and intradermal administration was essentially complete within one day. The peak HEMA levels in all tissues examined after 24 h were at least onemillion-fold less than known toxic levels.     

Latex allergy literature review: evidence for making military treatment facilities latex safe

Latex allergy has become the epidemic of the 1990s for health care workers, as indicated by a remarkable increase in its prevalence. This literature review provides a brief background to the latex problem, strategies for prevention and management, a cost analysis of glove substitution in a clinical setting, and the implications for the military environment. Primary care providers must recognize the financial, medico-legal, occupational, and personal ramifications of latex allergy. Risk managers should realize that moving to a latex-free environment will reduce liability.     

催产素对妊娠末期大鼠蜕膜细胞内游离钙的刺激作用

妊娠末期催产素刺激子宫蜕膜细胞产生与分娩有关的前列腺素,但其作用方式仍未知。本实验分离妊娠19d大鼠蜕膜细胞,测定了催产素作用后蜕膜细胞内游离钙的变化,结果加入0.001～1μmol·L^-1催产素后,蜕膜细胞内[Ca²⁺]i出现瞬息增加,其峰值与催产素浓度呈剂量依赖关系,且此作用有自身钝化现象。说明催产素可能激活妊娠末期大鼠蜕膜细胞内的肌醇磷酯蛋白激酶C系统。给妊娠末期大鼠ip硫酸去氢表雄酮钠盐后分离的蜕膜细胞,催产素作用引起[Ca²⁺]i瞬息增加峰值较对照升高。     

Gendered Ableism: Media Representations and Gender Role Beliefs’ Effect on Perceptions of Disability and Sexuality

This study explored the impact of advertisements featuring individuals either with or without a physical disability on attitudes towards sexuality and disability. In addition, the authors sought to determine whether there is a relationship between these attitudes and endorsement of traditional versus egalitarian gender role beliefs. A total of 707 online participants completed the Gender Role Belief Scale, then rated a series of ads featuring individuals with or without a disability (or served as a no ad control), and completed the Attitudes toward Sexuality Questionnaire and Perceptions of Sexuality Scale. Results demonstrated a complex relationship between gender role beliefs and exposure to advertisements on attitudes towards the sexuality of women and men with physical disabilities. As hypothesized, the endorsement of traditional gender role beliefs was related to more negative attitudes towards the sexuality of women with physical disabilities.     

Cell culture models of the human cornea - a comparative evaluation of their usefulness to determine ocular drug absorption in-vitro

Cell culture models of the cornea are continually developed to replace the isolated animal cornea for transcorneal drug absorption studies. The aim of this study was to determine and compare epithelial tightness and permeability of currently available corneal cell culture models to avoid interlaboratory variability and to assess their usefulness for in-vitro permeation studies. Pure epithelial cell culture models (CEPI, SIRC and HCE-T cell lines), primary cultures of human corneal epithelium (HCEpiC) and the two commercially available models (RHC and Epiocular), as well as organotypic human cornea constructs (HCC, HCC-HCE-T), were investigated and data were compared with those obtained from the excised bovine cornea. Barrier properties were assessed by measurements of transepithelial electrical resistance (TEER) and permeability of three passively absorbed substances (mannitol, testosterone and timolol maleate) with different physico-chemical properties. TEER experiments revealed weak barrier functions for all of the investigated epithelial models (相似文献