Intestinal antibody responses to a live oral poliovirus vaccine challenge among adults previously immunized with inactivated polio vaccine in Sweden.

BACKGROUND: Our understanding of the acquisition of intestinal mucosal immunity and the control of poliovirus replication and transmission in later life is still emerging. METHODS: As part of a 2011 randomised, blinded, placebo-controlled clinical trial of the experimental antiviral agent pocapavir (EudraCT 2011-004804-38), Swedish adults, aged 18-50 years, who had previously received four doses of inactivated polio vaccine (IPV) in childhood were challenged with a single dose of monovalent oral polio vaccine type 1 (mOPV1). Using faecal samples collected before and serially, over the course of 45 days, after mOPV1 challenge from a subset of placebo-arm participants who did not receive pocapavir (N=12), we investigated the kinetics of the intestinal antibody response to challenge virus by measuring poliovirus type 1-specific neutralising activity and IgA concentrations. RESULTS: In faecal samples collected prior to mOPV1 challenge, we found no evidence of pre-existing intestinal neutralising antibodies to any of the three poliovirus serotypes. Despite persistent high-titered vaccine virus shedding and rising serum neutralisation responses after mOPV1 challenge, intestinal poliovirus type 1-specific neutralisation remained low with a titer of ≤18.4 across all time points and individuals. Poliovirus types 1-specific, 2-specific and 3-specific IgA remained below the limit of detection for all specimens collected postchallenge. INTERPRETATION: In contrast to recent studies demonstrating brisk intestinal antibody responses to oral polio vaccine challenge in young children previously vaccinated with IPV, this investigation finds that adults previously vaccinated with IPV have only modest intestinal poliovirus type 1-specific neutralisation and no IgA responses that are measurable in stool samples following documented mOPV1 infection

Patients with usual vulvar intraepithelial neoplasia-related vulvar cancer have an increased risk of cervical abnormalities

Contains fulltext : 81890.pdf (publisher's version ) (Closed access)BACKGROUND: Vulvar squamous cell carcinoma (SCC) originates the following two pathways, related to differentiated (d) vulvar intraepithelial neoplasia (VIN) or to human papillomavirus (HPV)-related usual (u) VIN. Multicentric HPV infections (cervix, vagina and vulva) are common. We hypothesise that patients with a uVIN-related vulvar SCC more often have cervical high-grade squamous intraepithelial lesions (HSILs) compared with women with dVIN-related vulvar SCC. METHODS: All vulvar SCCs (201) were classified to be dVIN- (n=164) or uVIN related (n=37). Data with regard to the smear history and cervical histology were retrieved from PALGA, the nationwide Netherlands database of histo- and cytopathology. For HSIL cervical smears of which histology was taken, HPV DNA analysis on both the vulvar and cervical specimens was performed. RESULTS: At least one smear was available in 145 (72%) of the 201 patients. Patients with a uVIN-related vulvar SCC more often had an HSIL compared with patients with a dVIN-related SCC (35 vs 2%, P<0.001). A total of 10 of the 13 HSILs were histologically assessed and identical HPV types were found in the vulva and cervix. CONCLUSION: These data emphasise the necessity to differentiate between dVIN- and uVIN-related vulvar tumours and to examine the entire lower female ano-genital tract once an uVIN-related lesion is found

Limited duration of vaccine poliovirus and other enterovirus excretion among human immunodeficiency virus infected children in Kenya

<p>Abstract</p> <p>Background</p> <p>Immunodeficient persons with persistent vaccine-related poliovirus infection may serve as a potential reservoir for reintroduction of polioviruses after wild poliovirus eradication, posing a risk of their further circulation in inadequately immunized populations.</p> <p>Methods</p> <p>To estimate the potential for vaccine-related poliovirus persistence among HIV-infected persons, we studied poliovirus excretion following vaccination among children at an orphanage in Kenya. For 12 months after national immunization days, we collected serial stool specimens from orphanage residents aged <5 years at enrollment and recorded their HIV status and demographic, clinical, immunological, and immunization data. To detect and characterize isolated polioviruses and non-polio enteroviruses (NPEV), we used viral culture, typing and intratypic differentiation of isolates by PCR, ELISA, and nucleic acid sequencing. Long-term persistence was defined as shedding for ≥ 6 months.</p> <p>Results</p> <p>Twenty-four children (15 HIV-infected, 9 HIV-uninfected) were enrolled, and 255 specimens (170 from HIV-infected, 85 from HIV-uninfected) were collected. All HIV-infected children had mildly or moderately symptomatic HIV-disease and moderate-to-severe immunosuppression. Fifteen participants shed vaccine-related polioviruses, and 22 shed NPEV at some point during the study period. Of 46 poliovirus-positive specimens, 31 were from HIV-infected, and 15 from HIV-uninfected children. No participant shed polioviruses for ≥ 6 months. Genomic sequencing of poliovirus isolates did not reveal any genetic evidence of long-term shedding. There was no long-term shedding of NPEV.</p> <p>Conclusion</p> <p>The results indicate that mildly to moderately symptomatic HIV-infected children retain the ability to clear enteroviruses, including vaccine-related poliovirus. Larger studies are needed to confirm and generalize these findings.</p

The prognostic value of blood and lymph vessel parameters in lichen sclerosus for vulvar squamous cell carcinoma development: an immunohistochemical and electron microscopy study.

Contains fulltext : 87748.pdf (publisher's version ) (Closed access)OBJECTIVE: The objective of the study was to quantify vessel type and density in lichen sclerosus (LS) to find a marker for its malignant potential. STUDY DESIGN: Quantitative analysis was performed on paraffin-embedded tissue samples of 28 patients with LS (7 adjacent to vulvar squamous cell carcinoma, 21 solitary) and immunohistochemical staining for CD34 (vascular and lymphangiogenic lymph endothelial cells), D2-40 (lymphatic-specific marker), and alpha-SMA (pericyte marker). Electron microscopy was performed on fresh tissue. RESULTS: No significant differences in vessel density or other vessel parameters could be demonstrated between the 2 groups. In hyalinized lesions, vessel diameter, and alpha-SMA positivity was reduced compared with nonhyalinized lesions. Electron microscopy revealed detachment of pericytes from vascular endothelial cells and increased thickening of basement membrane, whereas endothelial cell function did not appear strongly impaired. CONCLUSION: Malignant potential of LS cannot be predicted by vessel characteristics. Hyalinization in LS is associated with pericyte detachment from the basal lamina of vascular endothelial cells.01 augustus 201

Management of vulvar cancers

AIM: The radical surgical approach in the treatment of vulvar cancer patients has led to a favorable prognosis for the majority of the patients with early stage squamous cell cancer. However, the morbidity is impressive, leading to more individualized treatment. The aim of this review is to give an overview of the management of vulvar cancer. METHODS: We have reviewed the literature on the modifications in treatment of vulvar cancer with the emphasis on surgery and radiotherapy for primary disease. RESULTS: While surgery is the cornerstone of treatment for early stage squamous cell vulvar cancer (with wide local excision and uni- or bilateral inguinofemoral lymphadenectomy via separate incisions as standard treatment), until now there has been a limited role for primary radiotherapy although this may be an attractive alternative for the inguinofemoral lymphadenectomy in the future. The sentinel lymph node procedure with the combined technique (preoperative lymphoscintigraphy with (99m)technetium-labeled nanocolloid and Patente Blue) is a promising staging technique for patients with vulvar cancer. The clinical implementation of the sentinel lymph node procedure and the role of additional histopathological techniques of the sentinel lymph nodes have to be investigated. In advanced vulvar cancer, chemoradiation followed by surgery should be regarded as the treatment of first choice for these patients. CONCLUSIONS: Due to the rarity of vulvar cancer it is quite clear that further studies will have to be performed by international collaborative groups. The sentinel lymph node procedure and primary radiotherapy are promising methods to reduce morbidity of treatment, but their safety needs to be studied in clinical trials

High levels of p53 expression correlate with DNA aneuploidy in (pre)malignancies of the vulva.

Contains fulltext : 88355.pdf (publisher's version ) (Closed access)The molecular pathogenesis of human papilloma virus-unrelated vulvar squamous cell carcinoma is not well known. Whether malignant progression of lichen sclerosus and differentiated vulvar intraepithelial neoplasia to vulvar squamous cell carcinoma could be accompanied by altered DNA content has not been studied extensively. DNA content in isolated nuclei of microdissected normal vulvar epithelium (n = 2), lichen sclerosus (n = 9), differentiated vulvar intraepithelial neoplasia (n = 13), and squamous cell carcinoma (n = 17) from 22 patients was measured via DNA image cytometry. For additional analysis, 6 differentiated vulvar intraepithelial neoplasia lesions were selected, bringing the number of patients to 28. p53 expression was determined by immunohistochemistry on consecutive tissue sections. Thirty-eight percent (5/13) of differentiated vulvar intraepithelial neoplasia lesions and 65% (11/17) of squamous cell carcinomas were DNA aneuploid or tetraploid. In lesions that contained differentiated vulvar intraepithelial neoplasia and adjacent squamous cell carcinoma, the ploidy status of differentiated vulvar intraepithelial neoplasia did not exceed that of squamous cell carcinoma. We observed a strong correlation between high p53 expression and DNA aneuploidy. This relation was also present at the level of a single nucleus, measured by sequential image cytometry of p53 immunohistochemistry followed by DNA image cytometry on formalin-fixed tissue sections. Similarly, we found p53-positive nonproliferating cells with increased DNA content in the superficial compartment of 6 additional solitary differentiated vulvar intraepithelial neoplasia lesions that were not associated with squamous cell carcinoma, indicating ascending aneuploid cells from the basal compartment. DNA ploidy measurements suggest that differentiated vulvar intraepithelial neoplasia has a higher malignant potential than lichen sclerosus and thus is a more likely precursor of squamous cell carcinoma. Furthermore, high p53 expression correlates with increased DNA content and aneuploidy; but it requires further research to unveil a possible causal relation.01 oktober 201