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Find video protocols related to scientific articles indexed in Pubmed.
Validation of whole slide imaging in the primary diagnosis of gynaecological pathology in a University Hospital.
J. Clin. Pathol.
PUBLISHED: 10-31-2014
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Experience in the use of whole slide imaging (WSI) for primary diagnosis in pathology is very limited. We aimed to determine the accuracy of interpretation of WSI compared with conventional light microscopy (CLM) in the diagnosis of routine gynaecological biopsies.
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Attributing Oncogenic Human Papillomavirus Genotypes to High-grade Cervical Neoplasia: Which Type Causes the Lesion?
Am. J. Surg. Pathol.
PUBLISHED: 10-30-2014
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Human papillomavirus (HPV) is found in most women with high-grade cervical intraepithelial neoplasia (CIN) 2/3 in cervical cytology and biopsies. Multiple high-risk HPV (hrHPV) genotypes are present in 15% to 50% of cytology samples. We have shown by laser-capture microscopy (LCM)-polymerase chain reaction (PCR) that each lesion is associated with a single hrHPV type. Attribution of hrHPV types to CIN2/3 is important to understand the oncogenic role of different types and the limitations of cytologic typing. We studied hrHPV genotypes in 257 women with histologic CIN2/3 referred on the basis of abnormal cytology. HPV typing was done on cytology and CIN2/3 biopsies. If the whole-tissue section of the biopsy was positive for multiple hrHPV types, LCM-PCR was performed. We found 181 (70%) single and 71 (28%) multiple hrHPV infections in cytology, with 5 (2%) cases HPV-positive only on whole-tissue section PCR. Of cases with multiple cytologic hrHPV infections, 47/71 (66%) showed a single type in CIN2/3 lesions. In total, in 232 of 257 (90%) women with CIN2/3, a single hrHPV type caused CIN2/3. One was nonattributable on the LCM level. The remaining 24 women had 2 or more contiguous or separated lesions, each associated with a single hrHPV infection. The probability of HPV16 being present in CIN2/3, if detected in cytology, was 0.96 (95% confidence interval=0.90-0.98). LCM-PCR confirms that only 9% of histologic CIN2/3 is associated with multiple hrHPV types, much less than cytology would indicate, and each lesion was associated with a single hrHPV infection.
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Malaria and HIV Infection in Mozambican Pregnant Women Are Associated With Reduced Transfer of Antimalarial Antibodies to Their Newborns.
J. Infect. Dis.
PUBLISHED: 09-30-2014
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?Malaria and human immunodeficiency virus (HIV) infection during pregnancy affect the transplacental transfer of antibodies against several pathogens from mother to fetus, although the effect of malaria and HIV infection on the transfer of antimalarial antibodies remains unclear.
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mRNA biomarker detection in liquid-based cytology: a new approach in the prevention of cervical cancer.
Mod. Pathol.
PUBLISHED: 09-05-2014
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Several high-risk human papillomavirus (HPV)-induced cell biomarkers have been proposed as possible candidates to identify patients harboring high-grade squamous intraepithelial lesions (HSILs) of the uterine cervix. We aimed to determine the feasibility of the detection of the mRNA of six biomarkers in cervical smear specimens obtained by liquid-based cytology and to evaluate whether this approach might be useful in the identification of patients with HSIL. One-hundred and twenty three women referred to colposcopy in the Hospital Clinic of Barcelona were included in the study. After a thorough study, including Pap test, high-risk HPV testing (Hybrid Capture 2 test), and colposcopy with directed biopsy and/or endocervical curettage, 48 patients were diagnosed with HSIL, whereas 75 were classified as negative (n=28), or harboring low-grade SIL (n=47). CDKN2A/p16, BIRC5, MMP9, TOP2A, MCM5, and MKI67 mRNA expression was analyzed by reverse transcription quantitative polymerase chain reaction in liquid-based cytology after the Pap test and Hybrid Capture 2 performance. The tissue expression of these biomarkers was analyzed by immunohistochemistry in the biopsy material. One-hundred and thirteen out of 123 (92%) liquid-based cytology yielded adequate material for mRNA analysis. TOP2A was the most sensitive (97%) biomarker for the detection of HSIL and CDKN2A/p16 the most specific (78%). The combination of TOP2A and CDKN2A/p16 showed a sensitivity of 96% (95% confidence interval (CI): 88-99) and a specificity of 71% (95% CI: 55-82). In the immunohistochemistry analysis, all biomarkers showed a high sensitivity but low specificity for HSIL, except CDKN2A/p16 which had a sensitivity of 100% and a specificity of 63%. The combination of TOP2A and CDKN2A/p16 showed a sensitivity of 100% (95% CI: 91-100) and a specificity of 43% (95% CI: 32-55). The detection of mRNA of cell biomarkers in liquid-based cytology material is feasible. The combination TOP2A and CDKN2A/p16 has a good balance between sensitivity and specificity for the detection of women with HSIL.Modern Pathology advance online publication, 5 September 2014; doi:10.1038/modpathol.2014.106.
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Usefulness of p16/Ki67 immunostaining in the triage of women referred to colposcopy.
Cancer Cytopathol
PUBLISHED: 04-24-2014
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This study compared the performance of p16/Ki67 dual-staining and human papillomavirus (HPV) testing in women referred to colposcopy and sought to determine the usefulness of a morphological evaluation of the double-stained cells.
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Undifferentiated uterine sarcoma: a rare, not well known and aggressive disease: report of 13 cases.
Arch. Gynecol. Obstet.
PUBLISHED: 03-10-2014
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Undifferentiated uterine sarcomas (UUS) are rare and aggressive tumor with scarce data on the outcome and best treatment. We aimed to describe the behavior among patients with UUS at our institution.
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Pathologic prognostic factors in stage I-III uterine carcinosarcoma treated with postoperative radiotherapy.
Arch. Gynecol. Obstet.
PUBLISHED: 02-28-2014
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To analyse the impact of prognostic factors on specific overall survival (SOS) after postoperative radiotherapy (P-RT) in carcinosarcomas.
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Oncogenic human papillomavirus-infected immature metaplastic cells and cervical neoplasia.
Am. J. Surg. Pathol.
PUBLISHED: 02-08-2014
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Persistent cervical high-risk human papillomavirus (HR-HPV) infection results in high-grade cervical intraepithelial neoplasia (CIN2/3) and cervical carcinoma. The susceptibility of the cervix to HPV carcinogenesis and the importance of HPV18 in cervical carcinoma despite relative infrequency in CIN2/3 could be linked to HR-HPV infection of immature metaplasia (IM) at the squamocolumnar junction. Atypical IM (AIM) is an equivocal category used to describe changes in IM suggestive of high-grade neoplasia, which causes diagnostic and management problems. We used laser capture microscopy combined with polymerase chain reaction in 24 women with HPV18, HPV16, or other HPV infections on cytologic analysis and a cervical loop electrosurgical excision procedure to locate HR-HPV in cervical tissue. HPV18-positive AIM and CIN2/3 were present in 7/12 cases with HPV18 on cytologic analysis. In 2 cases with HPV18 and other HPV types, HPV18 was only present in AIM and not in CIN2/3. HPV16-positive AIM was present in 3/7 and HPV16-positive CIN2/3 in 5/7 cases with HPV16. No cases had HPV16 AIM without CIN2/3. Other HR-HPV-positive AIM and CIN2/3 cases were present, respectively, in 1/6 and 5/6 cases positive for HR-HPV types other than HPV16/18. In a subset, 94% HPV18 AIM regions showed CK17 and p16 positivity, and 41% were CK7 positive. CIN2/3 and AIM with other HR-HPVs showed similar patterns. AIM was a particular feature of HPV18 infection in women with CIN2/3. HR-HPV infection of CK7/17-positive AIM expressing p16 was particularly seen for HPV18 with and without classical CIN2/3 and should be regarded as a high-grade precancer.
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Laparoscopic lymphadenectomy in advanced cervical cancer: prognostic and therapeutic value.
Int. J. Gynecol. Cancer
PUBLISHED: 11-01-2013
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Clinical benefit of surgical staging in locally advanced cervical cancer has not yet been proved. The goal of this study was to analyze the prognostic and therapeutic value of laparoscopic para-aortic lymphadenectomy with selective excision of suspicious pelvic nodes in patients with locally advanced cervical cancer.
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Reproducibility of current classifications of endometrial endometrioid glandular proliferations: further evidence supporting a simplified classification.
Histopathology
PUBLISHED: 07-03-2013
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To compare the reproducibility of the current (2003) World Health Organization (WHO), endometrial intraepithelial neoplasia (EIN) and European Working Group (EWG) classifications of endometrial endometrioid proliferations.
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Time trends of human papillomavirus types in invasive cervical cancer, from 1940 to 2007.
Int. J. Cancer
PUBLISHED: 06-20-2013
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Contribution over time of human papillomavirus (HPV) types in human cancers has been poorly documented. Such data is fundamental to measure current HPV vaccines impact in the years to come. We estimated the HPV type-specific distribution in a large international series of invasive cervical cancer (ICC) over 70 years prior to vaccination. Paraffin embedded ICC cases diagnosed between 1940 and 2007 were retrieved from eleven countries in Central-South America, Asia and Europe. Included countries reported to have low-medium cervical cancer screening uptake. Information on age at and year of diagnosis was collected from medical records. After histological confirmation, HPV DNA detection was performed by SPF-10/DEIA/LiPA25 (version1). Logistic regression models were used for estimating the adjusted relative contributions (RC) of HPV16 and of HPV18 over time. Among 4,771 HPV DNA positive ICC cases, HPV16 and HPV18 were the two most common HPVs in all the decades with no statistically significant variations of their adjusted-RC from 1940-59 to 2000-07 (HPV16-from 61.5 to 62.1%, and HPV18-from 6.9 to 7.2%). As well, the RC of other HPV types did not varied over time. In the stratified analysis by histology, HPV16 adjusted-RC significantly increased across decades in adenocarcinomas. Regarding age, cases associated to either HPV16, 18 or 45 were younger than those with other HPV types in all the evaluated decades. The observed stability on the HPV type distribution predicts a high and stable impact of HPV vaccination in reducing the cervical cancer burden in future vaccinated generations.
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High-risk human papillomavirus is transcriptionally active in a subset of sinonasal squamous cell carcinomas.
Mod. Pathol.
PUBLISHED: 04-19-2013
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It has been reported that high-risk human papillomavirus (HPV) is a causative agent of a subgroup of oropharyngeal carcinomas. In these tumors, the presence of the transcriptionally active HPV has been proved through the identification of HPV E6 or E7 messenger RNA (mRNA) transcripts. The aim of the study was to assess the HPV-active transcription in a series of sinonasal carcinomas, in correlation with the HPV DNA identification and the p16 immunohistochemistry. Seventy patients with squamous cell carcinomas of the sinonasal tract were included in the survey. The main clinicopathological characteristics were recorded. All tumors were investigated for HPV through the HPV DNA detection by PCR, using the SPF10 primers and by in situ hybridization, using the high-risk GenPoint probe (Dako, Glostrup, Denmark). HPV16 E7 mRNA transcripts detection was performed by RT-PCR in 27 cases. The immunostaining for p16 was performed in all cases. Fourteen carcinomas (20%) were positive for high-risk HPV by PCR: 13 HPV16 and one HPV35. In situ hybridization showed a dotted nuclear positivity in all these cases. HPV16 E7 mRNA was detected in seven tumors harboring HPV16; in the remaining HPV-positive cases, RNA did not reach the quality for analysis. Strong, diffuse positivity for p16 was observed only in the HPV-positive cases. The 14 HPV-positive squamous cell carcinomas were non-keratinizing or scarcely keratinizing tumors. No significant differences were found in terms of gender, age, or staging at diagnosis between HPV-positive and HPV-negative tumors. However, differences in disease-free survival and overall survival between both groups of patients were significant (P=0.004 and P=0.028, respectively). In conclusion, we have shown that HPV is the etiological agent of a subset of sinonasal carcinomas demonstrating the transcriptionally active HPV in these tumors. Immunostaining for p16 can be used as a surrogate marker to identify these tumors.Modern Pathology advance online publication, 13 September 2013; doi:10.1038/modpathol.2013.155.
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Rosetting in Plasmodium vivax: a cytoadhesion phenotype associated with anaemia.
PLoS Negl Trop Dis
PUBLISHED: 04-01-2013
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Plasmodium vivax can potentially lead to life-threatening episodes but the mechanisms underlying severe disease remain poorly defined. Cytoadhesion of infected erythrocytes may contribute to P. vivax sequestration and organ injury although its physiological impact is still unknown. Here, we aimed to describe clinically-relevant cytoadhesive phenotypes of P. vivax isolates.
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Endometrial stromal tumors: immunohistochemical and molecular analysis of potential targets of tyrosine kinase inhibitors.
Clin Sarcoma Res
PUBLISHED: 03-04-2013
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The systemic treatment of malignant endometrial stromal tumors (EST) is not well established. A few reports describe objective responses to imatinib, which suggest a novel therapeutic strategy for these tumors. Due to these facts, we aimed to perform a retrospective analysis of possible molecular targets of tyrosine kinase inhibitors (TKI) in EST: KIT, PDGFRA and EGFR.
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VAR2CSA signatures of high Plasmodium falciparum parasitemia in the placenta.
PLoS ONE
PUBLISHED: 01-01-2013
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Plasmodium falciparum infected erythrocytes (IE) accumulate in the placenta through the interaction between Duffy-binding like (DBL) domains of parasite-encoded ligand VAR2CSA and chondroitin sulphate-A (CSA) receptor. Polymorphisms in these domains, including DBL2X and DBL3X, may affect their antigenicity or CSA-binding affinity, eventually increasing parasitemia and its adverse effects on pregnancy outcomes. A total of 373 DBL2X and 328 DBL3X sequences were obtained from transcripts of 20 placental isolates infecting Mozambican women, resulting in 176 DBL2X and 191 DBL3X unique sequences at the protein level. Sequence alignments were divided in segments containing combinations of correlated polymorphisms and the association of segment sequences with placental parasite density was tested using Bonferroni corrected regression models, taking into consideration the weight of each sequence in the infection. Three DBL2X and three DBL3X segments contained signatures of high parasite density (P<0.003) that were highly prevalent in the parasite population (49-91%). Identified regions included a flexible loop that contributes to DBL3X-CSA interaction and two DBL3X motifs with evidence of positive natural selection. Limited antibody responses against signatures of high parasite density among malaria-exposed pregnant women could not explain the increased placental parasitemia. These results suggest that a higher binding efficiency to CSA rather than reduced antigenicity might provide a biological advantage to parasites with high parasite density signatures in VAR2CSA. Sequences contributing to high parasitemia may be critical for the functional characterization of VAR2CSA and the development of tools against placental malaria.
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Human papillomavirus genotype distribution in cervical cancer cases in Spain. Implications for prevention.
Gynecol. Oncol.
PUBLISHED: 09-14-2011
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Human papillomavirus (HPV) genotype distribution in invasive cervical cancer (ICC) is critical to guide the introduction and to assess the impact of HPV prophylactic vaccines. This study aims to provide specific information for Spain.
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Transcription of var genes other than var2csa in Plasmodium falciparum parasites infecting Mozambican pregnant women.
J. Infect. Dis.
PUBLISHED: 06-02-2011
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Increased susceptibility to Plasmodium falciparum infection during pregnancy has been attributed to the accumulation of infected erythrocytes in the placenta. This phenomenon is mediated by a var gene coding for VAR2CSA, which adheres to chondroitin sulphate A. However, the contribution of parasites transcribing other var genes to maternal infections has not been well characterized.
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Clinical, colposcopic and pathological characteristics of cervical and vaginal high-grade lesions negative for HPV by Hybrid Capture 2.
Gynecol. Oncol.
PUBLISHED: 03-15-2011
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Less than 5% of women with cervical or vaginal biopsy proven high-grade squamous intraepithelial lesions (HG-SIL) show a negative Hybrid Capture 2 (HC2) result. We analyzed 1) human papillomavirus (HPV) genotypes by PCR in order to determine whether these cases represent infections by common or unusual types, and 2) the clinical, colposcopic and pathological differential characteristics of these patients.
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Does human papillomavirus infection imply a different prognosis in vulvar squamous cell carcinoma?
Gynecol. Oncol.
PUBLISHED: 02-25-2011
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Two independent pathways in the development of vulvar squamous cell carcinoma (VSCC) have been described, one related to and the other independent of high-risk human papillomavirus (HR-HPV). The aim of our study was to evaluate whether the HPV status has a prognostic significance or can predict response to radiotherapy.
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Triaging Pap cytology negative, HPV positive cervical cancer screening results with p16/Ki-67 Dual-stained cytology.
Gynecol. Oncol.
PUBLISHED: 01-03-2011
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Testing for human papillomavirus (HPV) has been shown to increase the sensitivity and negative predictive value for detection of high-grade cervical intraepithelial neoplasia (CIN2+), either when used in conjunction with Pap cytology testing or alone. However, there is no satisfying clinical management algorithm for women testing Pap negative/HPV positive. We therefore evaluated the clinical utility of a novel dual biomarker-based approach (p16/Ki-67 Dual-stained cytology) for the identification of CIN2+ in women with Pap negative/HPV positive screening results, without the need to refer all women to immediate colposcopy.
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Impact of malaria at the end of pregnancy on infant mortality and morbidity.
J. Infect. Dis.
PUBLISHED: 01-03-2011
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There is some consensus that malaria in pregnancy may negatively affect infants mortality and malaria morbidity, but there is less evidence concerning the factors involved.
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Primary squamous cell carcinoma of the vagina: human papillomavirus detection, p16(INK4A) overexpression and clinicopathological correlations.
Histopathology
PUBLISHED: 12-21-2010
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To determine the role of human papillomavirus (HPV) in the pathogenesis of primary squamous cell carcinoma of the vagina (SCCVa), and to evaluate its clinicopathological significance.
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Colposcopy prediction of progression in human papillomavirus infections with minor cervical lesions.
Obstet Gynecol
PUBLISHED: 11-25-2010
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To evaluate the risk of progression to cervical intraepithelial neoplasia (CIN) grade 2 or 3 in women with positive human papillomavirus (HPV) testing and low-grade (low-grade squamous intraepithelial lesions), borderline (atypical squamous cells of undetermined significance), or no cervical lesions, and to determine the accuracy of initial colposcopy to predict progression.
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Persistence of Plasmodium falciparum parasites in infected pregnant Mozambican women after delivery.
Infect. Immun.
PUBLISHED: 11-01-2010
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Pregnant women are susceptible to Plasmodium falciparum parasites that sequester in the placenta. The massive accumulation of infected erythrocytes in the placenta has been suggested to trigger the deleterious effects of malaria in pregnant women and their offspring. The risk of malaria is also high during the postpartum period, although mechanisms underlying this susceptibility are not known. Here, we aimed to identify host factors contributing to the risk of postpartum infections and to determine the origin of postpartum parasites by comparing their genotypes with those present at the time of delivery. To address this, blood samples were collected at delivery (n = 402) and postpartum (n = 354) from Mozambican women enrolled in a trial of intermittent preventive treatment in pregnancy (IPTp). P. falciparum was detected by real-time quantitative PCR (qPCR), and the parasite merozoite surface protein 1 (msp-1) and msp-2 genes were genotyped. Fifty-seven out of 354 (16%) women were infected postpartum as assessed by qPCR, whereas prevalence by optical microscopy was only 4%. Risk of postpartum infection was lower in older women (odds ratio [OR] = 0.34, 95% confidence interval [CI] = 0.15 to 0.81) and higher in women with a placental infection at delivery (OR = 4.20, 95% CI = 2.19 to 8.08). Among 24 women with matched infections, 12 (50%) were infected postpartum with at least one parasite strain that was also present in their placentas. These results suggest that parasites infecting pregnant women persist after delivery and increase the risk of malaria during the postpartum period. Interventions that reduce malaria during pregnancy may translate into a lower risk of postpartum infection.
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Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study.
Lancet Oncol.
PUBLISHED: 10-15-2010
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Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer.
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Strain-specific spleen remodelling in Plasmodium yoelii infections in Balb/c mice facilitates adherence and spleen macrophage-clearance escape.
Cell. Microbiol.
PUBLISHED: 10-01-2010
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Knowledge of the dynamic features of the processes driven by malaria parasites in the spleen is lacking. To gain insight into the function and structure of the spleen in malaria, we have implemented intravital microscopy and magnetic resonance imaging of the mouse spleen in experimental infections with non-lethal (17X) and lethal (17XL) Plasmodium yoelii strains. Noticeably, there was higher parasite accumulation, reduced motility, loss of directionality, increased residence time and altered magnetic resonance only in the spleens of mice infected with 17X. Moreover, these differences were associated with the formation of a strain-specific induced spleen tissue barrier of fibroblastic origin, with red pulp macrophage-clearance evasion and with adherence of infected red blood cells to this barrier. Our data suggest that in this reticulocyte-prone non-lethal rodent malaria model, passage through the spleen is different from what is known in other Plasmodium species and open new avenues for functional/structural studies of this lymphoid organ in malaria.
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Osteopontin and alphavbeta3 integrin as markers of endometrial receptivity: the effect of different hormone therapies.
Reprod. Biomed. Online
PUBLISHED: 03-30-2010
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The osteopontin: alphavbeta3 integrin complex has been proposed as a means of distinguishing receptive from non-receptive endometrium in clinical practice, thus offering new directions for the development of contraceptive approaches targeted to the endometrium as well as a better understanding of occult causes of infertility in women. Histological dating and immunohistochemical study were performed in control and study cycles in seven groups of women including 10 subjects per group and who received clomiphene citrate, ovarian stimulation for IVF, oral contraception, dehydrogesterone for endometrial luteal phase defect, two different regimens of hormone replacement therapy, or no treatment. Ten healthy fertile women served as a general control group. Osteopontin and alphavbeta3 integrin expression in the human endometrium was closely related to endometrial maturation and this was irrespective of the endometrium being in-phase or out-of-phase and the hormonal treatment (or no treatment) received. In conclusion, immunohistochemical assessment of the endometrium indicates that the use of osteopontin and alphavbeta3 integrin or the osteopontin: alphavbeta3 integrin complex as targets for the development of contraceptive approaches or the understanding of the pathogenesis of female infertility offer little benefit compared with simple histological dating.
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Conjunctive p16INK4a testing significantly increases accuracy in diagnosing high-grade cervical intraepithelial neoplasia.
Am. J. Clin. Pathol.
PUBLISHED: 02-16-2010
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The histopathologic interpretation of cervical intraepithelial neoplasia (CIN) is subject to a high level of interobserver variability and a substantial number of false-positive and false-negative results. We assessed the impact of the conjunctive interpretation of p16(INK4a)-immunostained slides on the accuracy of community-based pathologists in diagnosing high-grade cervical intraepithelial neoplasia (CIN; CIN 2 and CIN 3) in biopsy specimens. Twelve pathologists rendered independent diagnoses on a set of 500 H&E-stained cervical punch and conization specimens. Results were compared with a dichotomized "gold standard" established by consensus of 3 gynecopathology experts. When p16(INK4a)-immunostained slides were added and conjunctively interpreted with the H&E-stained slides, a significant increase in diagnostic accuracy for the detection of high-grade CIN was observed (P = .0004). Sensitivity for high-grade CIN was increased by 13%, cutting the rate of false-negative results in half. Agreement of community-based pathologists in diagnosing high-grade CIN was significantly improved (mean kappa values advanced from 0.566 to 0.749; P < .0001). Reproducibility of p16(INK4a) stain interpretation was excellent (kappa = 0.899). Our results show that conjunctive interpretation of p16(INK4a)-stained slides could significantly improve the routine interpretation of cervical histopathology.
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How to deal with prognostic factors and radiotherapy results in uterine neoplasms with a sarcomatous component?
Clin Transl Oncol
PUBLISHED: 10-16-2009
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Uterine tumours with a sarcomatous component are rare neoplasms with a wide pathologic heterogeneity in which the stage is the main prognostic factor. These aspects and their aggressiveness make the analysis of prognostic factors and radiotherapy difficult. The aim of this study was to evaluate the prognostic factors by stages and to assess the impact of prognostic factors and the effect of radiotherapy on the outcome of the disease.
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HPV-negative vulvar intraepithelial neoplasia (VIN) with basaloid histologic pattern: an unrecognized variant of simplex (differentiated) VIN.
Am. J. Surg. Pathol.
PUBLISHED: 09-05-2009
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Vulvar intraepithelial neoplasia (VIN) is classified into 2 clinicopathologic subtypes, classic, related to human papillomavirus (HPV) infection and affecting relatively young women, and simplex (differentiated), negative for HPV and affecting elderly women. Histologically, classic VIN may be basaloid and characterized by a replacement of the whole epidermis by a homogeneous population of small, "undifferentiated" keratinocytes, which are diffusely positive for p16(INK4a) and negative for p53. Simplex VIN is characterized by atypia of the basal layer with high degree of cellular differentiation and shows negative staining for p16(INK4a) and frequent positivity for p53. Simplex VIN is frequently associated with squamous cell hyperplasia and lichen sclerosus. From a series of 110 invasive squamous cell carcinomas of the vulva negative for HPV by highly sensitive polymerase chain reaction, 51 had VIN lesions located at least 1 cm away from the tumor. In 4 (7.8%) cases, the VIN had basaloid histologic features. All cases showed obvious architectural disorganization with a homogeneous population of basaloid, undifferentiated keratinocytes with scanty cytoplasm replacing the whole epidermis. Immunohistochemically, all cases were negative for p16(INK4a) and strongly positive for p53 with suprabasilar extension of positive cells. All patients were postmenopausal (median age 61.0 y; range, 45-76). Squamous cell hyperplasia was identified in 1 case and lichen sclerosus in 1 case. The invasive squamous cell carcinoma was of keratinizing type in 3 cases and basaloid in 1 case. In conclusion, simplex, HPV-negative VIN may occasionally have basaloid morphology. Immunostaining for p16(INK4a) and p53 protein may be helpful in the identification of these lesions and the differential diagnosis with classic, HPV-positive basaloid VIN.
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Human papillomaviruses are identified in a subgroup of sinonasal squamous cell carcinomas with favorable outcome.
Cancer
PUBLISHED: 04-15-2009
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The role of human papillomavirus (HPV) in the pathogenesis of squamous cell carcinomas (SCCs) of the sinonasal tract and its clinicopathological implications were evaluated.
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p16 INK4a immunostaining identifies occult CIN lesions in HPV-positive women.
Int. J. Gynecol. Pathol.
PUBLISHED: 03-04-2009
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To evaluate whether p16 staining could help to recognize underestimated cervical intraepithelial neoplasia (CIN) in women positive for high-risk human papillomavirus (HR-HPV) with negative biopsy. Out of 1,259 women undergoing a histologic study and a simultaneous HR-HPV detection using the Hybrid Capture 2 test, we selected all patients testing positive for HR-HPV and having a negative biopsy (n=139), as well as all women testing negative for HR-HPV with a biopsy of either CIN 1 (26 cases) or CIN 2 to 3 (11 cases). Of the remaining 1,083 women, we randomly selected for the purpose of controls, 50 cases negative for HR-HPV with negative biopsy and 100 cases positive for HR-HPV and with biopsy of CIN (50 CIN 1, 50 CIN 2-3). In all cases, immunohistochemical staining for p16 and a second evaluation of the initial biopsy was carried out. Thirty-four out of 139 biopsies (24.5%) testing positive for HR-HPV but having a negative biopsy were positive for p16. Thirty of these cases (21.6%) were classified as harboring a CIN (11 CIN 1, 19 CIN 2/3) after reevaluation. Both the number of cases reclassified as CIN of any grade, or as CIN 2/3, were significantly higher for cases with HR-HPV load above 100 relative light unit (P<0.005). Particular attention should be paid to biopsies from patients having positive Hybrid Capture 2. The risk of harboring undetected CIN of any type or CIN 2/3 is significantly higher for patients with high HR-HPV load. Immunostaining with p16 should be considered as a highly desirable addition to the histologic evaluation of cervical biopsy specimens in HR-HPV-positive women.
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Value of p16(INK4a) as a marker of progression/regression in cervical intraepithelial neoplasia grade 1.
Am. J. Obstet. Gynecol.
PUBLISHED: 02-12-2009
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The objective of this study was to evaluate the usefulness of p16(INK4a) staining to classify cervical intraepithelial neoplasia grade 1 according to its progression/regression risk.
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Clinico-pathological discrepancies in the diagnosis of causes of maternal death in sub-Saharan Africa: retrospective analysis.
PLoS Med.
PUBLISHED: 01-10-2009
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Maternal mortality is a major public-health problem in developing countries. Extreme differences in maternal mortality rates between developed and developing countries indicate that most of these deaths are preventable. Most information on the causes of maternal death in these areas is based on clinical records and verbal autopsies. Clinical diagnostic errors may play a significant role in this problem and might also have major implications for the evaluation of current estimations of causes of maternal death.
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Pathways of vulvar intraepithelial neoplasia and squamous cell carcinoma.
Histopathology
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Vulvar squamous cell carcinoma (VSCC) accounts for >90% of the malignant tumours of the vulva. Most VSCCs originate in intraepithelial lesions, named vulvar intraepithelial neoplasia (VIN), that precede the development of VSCC by a variable period of time. Strong evidence has accumulated showing that there are two different aetiopathogenic pathways for the development of VSCC and VIN, one associated with infection by human papillomavirus (HPV), and a second independent of HPV infection. These two different types of VSCC have different epidemiological, pathological and clinical characteristics, and should therefore be considered as two separate entities. Histologically, HPV-associated VSCCs are of the basaloid or warty type, and arise from VIN of the usual type. Inactivation of p53 and the retinoblastoma tumour suppressor gene product by the viral gene products E6 and E7 is involved in the process of malignant transformation. HPV-independent VSCCs are histologically keratinizing, are associated with differentiated VIN and lichen sclerosus, and frequently show mutations of p53. p16(INK4a) and p53 immunostaining can be useful for classifying VSCC into HPV-associated or HPV-independent. Although large, multicentre studies are needed to definitively assess the involvement of HPV in the prognosis of VSCC, most studies have not found clear differences in survival between HPV-associated and HPV-independent tumours.
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Predictors of absence of cervical intraepithelial neoplasia in the conization specimen.
Gynecol. Oncol.
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Over 10% of women who undergo conization for cervical intraepithelial neoplasia (CIN) show no lesion in the surgical specimen. We aimed to determine whether these patients can be identified before conization using clinical, virological and/or cyto-histological characteristics, to avoid unnecessary treatment.
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Transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR): a new method for sentinel lymph node detection in endometrial cancer.
Gynecol. Oncol.
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The objective of this prospective study was to determine the feasibility, safety and performance of a new method for sentinel lymph node (SLN) detection in endometrial cancer (EC) using transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR).
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Placental infection with Plasmodium vivax: a histopathological and molecular study.
J. Infect. Dis.
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Evidence of the presence of Plasmodium vivax in the placenta is scarce and inconclusive. This information is relevant to understanding whether P. vivax affects placental function and how it may contribute to poor pregnancy outcomes.
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Differences in human papillomavirus type distribution in high-grade cervical intraepithelial neoplasia and invasive cervical cancer in Europe.
Int. J. Cancer
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Knowledge of differences in human papillomavirus (HPV)-type prevalence between high-grade cervical intraepithelial neoplasia (HG-CIN) and invasive cervical cancer (ICC) is crucial for understanding the natural history of HPV-infected cervical lesions and the potential impact of HPV vaccination on cervical cancer prevention. More than 6,000 women diagnosed with HG-CIN or ICC from 17 European countries were enrolled in two parallel cross-sectional studies (108288/108290). Centralised histopathology review and standardised HPV-DNA typing were applied to formalin-fixed paraffin-embedded cervical specimens dated 2001-2008. The pooled prevalence of individual HPV types was estimated using meta-analytic methods. A total of 3,103 women were diagnosed with HG-CIN and a total of 3,162 with ICC (median ages: 34 and 49 years, respectively), of which 98.5 and 91.8% were HPV-positive, respectively. The most common HPV types in women with HG-CIN were HPV16/33/31 (59.9/10.5/9.0%) and in ICC were HPV16/18/45 (63.3/15.2/5.3%). In squamous cell carcinomas, HPV16/18/33 were most frequent (66.2/10.8/5.3%), and in adenocarcinomas, HPV16/18/45 (54.2/40.4/8.3%). The prevalence of HPV16/18/45 was 1.1/3.5/2.5 times higher in ICC than in HG-CIN. The difference in age at diagnosis between CIN3 and squamous cervical cancer for HPV18 (9 years) was significantly less compared to HPV31/33/other (23/20/17 years), and for HPV45 (1 year) than HPV16/31/33/other (15/23/20/17 years). In Europe, HPV16 predominates in both HG-CIN and ICC, whereas HPV18/45 are associated with a low median age of ICC. HPV18/45 are more frequent in ICC than HG-CIN and associated with a high median age of HG-CIN, with a narrow age interval between HG-CIN and ICC detection. These findings support the need for primary prevention of HPV16/18/45-related cervical lesions.
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How hidden can malaria be in pregnant women? Diagnosis by microscopy, placental histology, polymerase chain reaction and detection of histidine-rich protein 2 in plasma.
Clin. Infect. Dis.
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Accurate diagnosis of malaria infection during pregnancy remains challenging because of low parasite densities and placental sequestration of Plasmodium falciparum. The performance of different methods to detect P. falciparum in pregnancy and the clinical relevance of undetected infections were evaluated.
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Human papillomavirus as a favorable prognostic biomarker in squamous cell carcinomas of the vagina.
Gynecol. Oncol.
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Recent evidence has confirmed two independent pathways in the development of vaginal squamous cell carcinoma (VaSCC): one related to and the other independent of human papillomavirus (HPV). The aim of our study was to evaluate whether HPV status has prognostic significance in this neoplasm.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.