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  • 1
    Unknown
    Sudbury, Mass. : Jones and Bartlett Publishers
    Call number: C020:112
    Keywords: Epidemiologic Methods ; Epidemiology
    Pages: xiii, 489 p. : ill.
    Edition: 2nd ed.
    ISBN: 9780763729271
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    C020:112 departmental collection or stack – please contact the library
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  • 2
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    Burlington, Mass. : Jones and Bartlett Learning
    Call number: WA100:49(3) ; C020:147 ; G110:28
    Keywords: Epidemiologic Methods ; Epidemiology
    Pages: xiii, 489 p. : ill.
    Edition: 3rd ed.
    ISBN: 9781449604691
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    WA100:49(3) available
    C020:147 departmental collection or stack – please contact the library
    G110:28 departmental collection or stack – please contact the library
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  • 3
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Sensitization to latex has become a major problem in children with spina bifida. Life-threatening reactions may occur in these patients, therefore the search of latex sensitization must be an active task in all of these children.〈section xml:id="abs1-2"〉〈title type="main"〉ObjectiveTo design an approach for the diagnosis of latex sensitization in children with spina bifida.〈section xml:id="abs1-3"〉〈title type="main"〉MethodsWe studied 100 consecutive unselected patients. Skin prick tests with a commercial latex extract were performed, latex-specific serum immunoglobulin (Ig) E was determined by CAP test, and risk factors were studied. Originally, patients with an area of latex skin test 〉 50% of the area of histamine and/or CAP class ≥ 3 were considered sensitized to latex. Diagnostic tests were also performed in a control group of 51 atopic and nonatopic children.〈section xml:id="abs1-4"〉〈title type="main"〉ResultsAfter performing a receiver-operating characteristics curve for both tests we recommend skin tests 〉 25% of the area of histamine (sensitivity − SEN = 79%, specificity − SPE = 100%, positive predictive value − PPV = 100%, negative predictive value − NPV = 90%), or CAP class ≥ 2 (SEN = 88%, SPE = 100%, PPV = 100%, NPV = 94%) as diagnostic cut-off points. The anamnesis had a SEN of 44% for diagnosis, and a SPE of 100%. Latex sensitization was associated with more than 5 operations (OR = 8, 95% CI = 3–21.3), a personal history of atopy (OR = 11.5, 95% CI = 2.3–57.1), and serum total IgE ≥ 2 z-units (OR = 4, 95% CI = 1.6–10).〈section xml:id="abs1-5"〉〈title type="main"〉ConclusionFor the routine evaluation of children with spina bifida, we propose a diagnostic algorithm with skin prick tests as a first step and CAP second.
    Type of Medium: Electronic Resource
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  • 4
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  G-I-N Conference 2012; 20120822-20120825; Berlin; DOCO43 /20120710/
    Publication Date: 2012-07-11
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 5
    Keywords: BOVINE PAPILLOMAVIRUS ; cervical intraepithelial neoplasia ; VIRUS-LIKE PARTICLES ; CANCER-PATIENTS ; TUMOR-GROWTH ; PHASE-II TRIAL ; REGULATORY T-CELLS ; HIGH-GRADE ; VACCINIA VIRUS ; LONG PEPTIDES
    Abstract: Recently, two prophylactic vaccines against the most significant oncogenic human papillomaviruses (HPV; 16 and 18) became available that efficiently protect against persistent HPV infection and cancer precursors. However, clinical trials performed with these vaccines did not provide evidence that they would influence the natural history of prevalent HPV infections, that is, their eventual malignant progression. Because, even under the optimistic assumption of high vaccine coverage, a significant reduction of cancer incidence can only be expected after two decades, there is a need for immune therapeutic strategies to be offered to persistently infected individuals who do not benefit from the prophylactic vaccines. Here, we describe the reasons for failure of most of the published approaches to HPV-specific therapies, highlight promising developments and present our view for future developments.
    Type of Publication: Journal article published
    PubMed ID: 21041909
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  • 6
    Keywords: IN-VITRO ; TRANSDUCTION ; INDUCTION ; IMMUNE-RESPONSES ; NEUTRALIZING ANTIBODIES ; PARTICLES ; HUMAN-IMMUNODEFICIENCY-VIRUS ; CYTOTOXIC T-LYMPHOCYTES ; AAV VECTORS ; CARDIAC GENE-TRANSFER
    Abstract: Background: Cervical cancer is the second most frequent cancer among woman worldwide and is considered to be caused by infection with high-risk papilloma viruses. Genetic immunization using recombinant adeno-associated virus (rAAV) vectors has shown great promise for vaccination against human papillomavirus (HPV) infections. Methods: rAAV5, -8 and -9 vectors expressing an HPV16 L1/E7 fusion gene were generated and applied intranasally for combined prophylactic and therapeutic vaccination of mice. Results: The rAAV5 and the rAAV9 vectors showed efficient induction of both humoral and cellular immune responses, whereas rAAV8 failed to immunize mice by the intranasal route. The L1-specific immune response evoked by expression of the L1/E7 fusion gene, however, was lower than that evoked by expression of the L1 antigen alone. This deficiency could be compensated by application of Escherichia coli heat-labile enterotoxin or monophsphoryl lipid as adjuvant upon vaccination with rAAV5-L1/E7. Coimmunization of rAAV9-L1/E7 with rAAV5-L1 or boosting of rAAV9-L1/E7 with rAAV5-L1 strongly increased L1-specific neutralizing antibody titres to levels above those achieved by vaccination with vectors expressing L1 alone. Both vectors elicited a vibrant cytotoxic T-lymphocyte response against L1 or E7. Nasal immunization with rAAV5 or rAAV9 was superior to vaccination with HPV16-L1 virus-like particles (VLPs) or HPV16-L1/E7 CVLPs with respect to humoral and cellular immune responses. Vaccination with the rAAV vectors led to a significant protection of animals against a challenge with different HPV tumour cell lines. Conclusions: Our results show that rAAV5 and rAAV9 vectors are promising candidates for a non-invasive nasal vaccination strategy.
    Type of Publication: Journal article published
    PubMed ID: 20032542
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  • 7
    Keywords: SPECTROMETRY ; MONTE-CARLO ; AMBIENT ; FIELDS ; Bonner Sphere System ; DOSIMETER ; GLOW CURVE ANALYSIS ; ROOMS
    Abstract: Neutron peripheral contamination in patients undergoing high-energy photon radiotherapy is considered as a risk factor for secondary cancer induction. Organ-specific neutron-equivalent dose estimation is therefore essential for a reasonable assessment of these associated risks. This work aimed to develop a method to estimate neutron-equivalent doses in multiple organs of radiotherapy patients. The method involved the convolution, at 16 reference points in an anthropomorphic phantom, of the normalized Monte Carlo neutron fluence energy spectra with the kerma and energy-dependent radiation weighting factor. This was then scaled with the total neutron fluence measured with passive detectors, at the same reference points, in order to obtain the equivalent doses in organs. The latter were correlated with the readings of a neutron digital detector located inside the treatment room during phantom irradiation. This digital detector, designed and developed by our group, integrates the thermal neutron fluence. The correlation model, applied to the digital detector readings during patient irradiation, enables the online estimation of neutron-equivalent doses in organs. The model takes into account the specific irradiation site, the field parameters (energy, field size, angle incidence, etc) and the installation (linac and bunker geometry). This method, which is suitable for routine clinical use, will help to systematically generate the dosimetric data essential for the improvement of current risk-estimation models.
    Type of Publication: Journal article published
    PubMed ID: 22971664
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  • 8
    Keywords: CANCER ; CELLS ; tumor ; BLOOD ; CELL ; human ; MODEL ; MODELS ; COMMON ; RISK ; PROTEIN ; PROTEINS ; TUMORS ; PATIENT ; DNA ; MECHANISM ; E7 ; papillomavirus ; ASSOCIATION ; antibodies ; antibody ; ASSAY ; PLASMA ; etiology ; cervical cancer ; CERVICAL-CANCER ; COUNTRIES ; PCR ; cancer risk ; RISK FACTOR ; human papillomavirus ; HPV ; E6 ; HPV16 ; HUMAN-PAPILLOMAVIRUS ; SQUAMOUS-CELL CARCINOMA ; HEAD ; POLYMERASE-CHAIN-REACTION ; case-control studies ; TOBACCO ; L1 ; POLYMERASE CHAIN-REACTION ; SMOKERS ; EARLY PROTEINS ; HPV TYPE-16 ; INTERVIEW ; INVASIVE CERVICAL-CANCER ; MULTICENTER ; NECK CANCERS ; ORAL CAVITY ; RAPID DETECTION ; TONSILLAR CARCINOMAS
    Abstract: Background: Human papillomavirus (HPV), the causal agent of cervical cancer, appears to be involved in the etiology of cancer of the oral cavity and oropharynx. To investigate these associations, we conducted a multicenter case-control study of cancer of the oral cavity and oropharynx in nine countries. Methods: We recruited 1670 case patients (1415 with cancer of the oral cavity and 255 with cancer of the oropharynx) and 1732 control subjects and obtained an interview, oral exfoliated cells, and blood from all participants and fresh biopsy specimens from case patients. HPV DNA was detected by polymerase chain reaction (PCR). Antibodies against HPV16 L1, E6, and E7 proteins in plasma were detected with enzyme-linked immunosorbent assays. Multivariable models were used for case-control and case-case comparisons. Results: HPV DNA was detected in biopsy specimens of 3.9% (95% confidence interval [CI] = 2.5% to 5.3%) of 766 cancers of the oral cavity with valid PCR results and 18.3% (95% CI = 12.0% to 24.7%) of 142 cancers of the oropharynx (oropharynx and tonsil combined) with valid PCR results. HPV DNA in cancer biopsy specimens was detected less frequently among tobacco smokers and paan chewers and more frequently among subjects who reported more than one sexual partner or who practiced oral sex. HPV16 DNA was found in 94.7% of HPV DNA-positive case patients. HPV DNA in exfoliated cells was not associated with cancer risk or with HPV DNA detection in biopsy specimens. Antibodies against HPV16 L1 were associated with risk for cancers of the oral cavity (odds ratio [OR] = 1.5, 95% CI = 1.1 to 2.1) and the oropharynx (OR = 3.5, 95% CI = 2.1 to 5.9). Antibodies against HPV16 E6 or E7 were also associated with risk for cancers of the oral cavity (OR = 2.9, 95% CI = 1.7 to 4.8) and the oropharynx (OR = 9.2. 95% CI = 4.8 to 17.7). Conclusions: HPV appears to play an etiologic role in many cancers of the oropharynx and possibly a small subgroup of cancers of the oral cavity. The most common HPV type in genital cancers (HPV16) was also the most common in these tumors. The mechanism of transmission of HPV to the oral cavity warrants further investigation
    Type of Publication: Journal article published
    PubMed ID: 14652239
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  • 9
    Keywords: TRANSDUCTION ; IDENTIFICATION ; VECTORS ; MONOCLONAL-ANTIBODIES ; AAV SEROTYPES ; ADENOVIRUS ; nucleolus ; ELECTRON CRYOMICROSCOPY ; HUMAN GENE-THERAPY ; TYPE-5 RNA
    Abstract: Adeno-associated virus type 2 (AAV2) capsid assembly requires the expression of a virally encoded assembly-activating protein (AAP). By providing AAP together with the capsid protein VP3, capsids are formed that are composed of VP3 only. Electron cryomicroscopy analysis of assembled VP3-only capsids revealed all characteristics of the wild-type AAV2 capsids. However, in contrast to capsids assembled from VP1, VP2, and VP3, the pores of VP3-only capsids were more restricted at the inside of the 5-fold symmetry axes, and globules could not be detected below the 2-fold symmetry axes. By comparing the capsid assembly of several AAV serotypes with AAP protein from AAV2 (AAP-2), we show that AAP-2 is able to efficiently stimulate capsid formation of VP3 derived from several serotypes, as demonstrated for AAV1, AAV2, AAV8, and AAV9. Capsid formation, by coexpressing AAV1-, AAV2-, or AAV5-VP3 with AAP-1, AAP-2, or AAP-5 revealed the ability of AAP-1 and AAP-2 to complement each other in AAV1 and AAV2 assembly, whereas for AAV5 assembly more specific conditions are required. Sequence alignment of predicted AAP proteins from the known AAV serotypes indicates a high degree of homology of all serotypes to AAP-2 with some divergence for AAP-4, AAP-5, AAP-11, and AAP-12. Immunolocalization of assembled capsids from different serotypes confirmed the preferred nucleolar localization of capsids, as observed for AAV2; however, AAV8 and AAV9 capsids could also be detected throughout the nucleus. Taken together, the data show that AAV capsid assembly of different AAV serotypes also requires the assistance of AAP proteins.
    Type of Publication: Journal article published
    PubMed ID: 21917944
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  • 10
    Keywords: IN-VIVO ; TRANSDUCTION ; GENE-TRANSFER ; IMMUNE-RESPONSES ; NEUTRALIZING ANTIBODIES ; CERVICAL-CANCER ; RECOMBINANT ADENOASSOCIATED VIRUS ; HUMAN-IMMUNODEFICIENCY-VIRUS ; VIRAL VECTOR ; NASAL EPITHELIA
    Abstract: Abstract Cervical cancer is the second most common cancer in women worldwide. Persistent high-risk human papillomavirus (HPV) infection has been identified as the causative event for the development of this type of cancer. Recombinant adeno-associated viruses (rAAVs) are currently being developed and evaluated as vaccine vector. In previous work, we demonstrated that rAAVs administered intranasally in mice induced high titers and long-lasting neutralizing antibodies against HPV type 16 (HPV16). To extend this approach to a more human-related species, we immunized rhesus macaques (Macaca mulatta) with AAVs expressing an HPV16 L1 protein using rAAV5 and 9 vectors in an intranasal prophylactic setting. An rAAV5-L1 vector followed by a boost with rAAV9-L1 induced higher titers of L1-specific serum antibodies than a single rAAV5-L1 immunization. L1-specific antibodies elicited by AAV9 vector neutralized HPV16 pseudovirions and persisted for at least 7 months post immunization. Interestingly, nasal application of rAAV9 was immunogenic even in the presence of high AAV9 antibody titers, allowing reimmunization with the same serotype without prevention of the transgene expression. Two of six animals did not respond to AAV-mediated intranasal vaccination, although they were not tolerant, as both developed antibodies after intramuscular vaccination with HPV16 virus-like particles. These data clearly show the efficacy of an intranasal immunization using rAAV9-L1 vectors without the need of an adjuvant. We conclude from our results that rAAV9 vector is a promising candidate for a noninvasive nasal vaccination strategy.
    Type of Publication: Journal article published
    PubMed ID: 22401308
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