Direct comparison of two vaginal self-sampling devices for the detection of human papillomavirus infections.

BACKGROUND AND OBJECTIVES: Two devices for vaginal self-sampling of dry cell material (Evalyn Brush, Rovers Medical Devices; Qvintip, Aprovix) were compared using the Abbott RealTime High Risk HPV test. STUDY DESIGN: Both self-sampling devices (change of order with every patient) including instructions for use and a questionnaire were handed to 146 patients in a colposcopy clinic prior to scheduled colposcopies with collection of cervical reference specimens by gynaecologists using a broom-like device. Matched self-collected and physician collected specimens were transferred to ThinPrep medium and tested for the presence of hr-HPV. Biopsies were taken if indicated by colposcopy. RESULTS: Evaluation of 136 patients with complete data (136/146; 93.2%) showed high agreement of overall hr-HPV detection rates between self-collected and clinician-collected specimens (Evalyn: 91.2% [kappa 0.822]; Qvintip: 89.0% [kappa 0.779]). Colposcopy and histological evaluation revealed 55 women without cervical intraepithelial neoplasia (CIN), 32 CIN1, 34 CIN2, 14 CIN3 and one adenocarcinoma in situ. Hr-HPV testing detected all CIN3+ cases on the clinician-taken or Evalyn self-samples (14/14) and 93% of them on the Qvintip samples (13/14). There was no significant difference regarding the sensitivity for CIN2+ or CIN3+ and specificity of hr-HPV testing on self- vs. clinician samples and on Evalyn vs. Qvintip. Based on signal intensities of ß-globin, the observed DNA concentration with Evalyn samples (mean CN: 22.0; 95%-CI: 21.5-22.6) was found to be significantly higher compared to that of Qvintip samples (mean CN: 23.8; 95%-CI 23.2-24.4), regardless of the order of self-sampling (p<0.0001). Most women considered self-sampling easy and comfortable. Qvintip was considered easier than the Evalyn Brush to understand (p<0.001) and to use (p=0.002). DISCUSSION: This study confirms that hr-HPV testing with a clinically validated PCR-based HPV assay is as accurate on self-samples as on clinician-samples without significant difference between both self-sampling devices.

WITHDRAWN: Comparative evaluation of two vaginal self-sampling devices for the detection of human papillomavirus infections.

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Low-flux hemodialysis suppresses interferon-gamma production: the possible role of beta2-microglobulin.

UNLABELLED: Interferon-gamma (IFN-gamma) is required for the acquired immune response involving maturation and activation of antigen-presenting cells (APC); both IFN-gamma production and activation of APC are impaired in ESRD patients on low-flux hemodialysis (HD). High levels of uremic toxins including beta2-microglobulin (beta2M) are thought to play a role in immunosuppression. PATIENTS AND METHODS: To test this hypothesis, we conducted an A-B-A crossover study to examine the influence of high-flux HD (A) versus low-flux HD (B) in ESRD patients (n = 14) using biocompatible synthetic dialyzer membranes (Polyamix(R), Gambro, Hechingen, Germany) and ultrafiltered bicarbonate-buffered dialysis fluid. Each study period lasted 6 months and at the end of each period, Kt/V urea, plasma levels of albumin, C-reactive protein (CRP) and beta2M were determined. In addition, production of IFN-gamma induced by heat-killed Staphylococcus epidermidis (Staph epi) was performed in whole blood cultures. RESULTS: Kt/V urea (mean +/- SEM) was 1.45 +/- 0.06 in Period A, 1.36 +/- 0.07* in Period B, and 1.51 +/- 0.07 in Period A' (*p < 0.01). beta2M resting levels increased from 26.6 +/- 1.42 mg/l in Period A to 34.7 +/- 2.30* mg/l in Period B, and decreased to 21.6 +/- 1.07 mg/l at the end of Period A' (*p < 0.0001). Albumin and CRP levels did not differ significantly. Staph epi-induced IFN-gamma production was 1.2 +/- 0.39 ng/1,000 PBMC at the end of Period A, 0.34 +/- 0.10 ng/1,000 PBMC* in Period B, and 2.71 +/- 0.67 ng/1,000 PBMC at the end of Period A' (*p < 0.05). There was an inverse correlation between b2M levels and whole blood IFN-gamma production (R2 = 0.26). CONCLUSION: High levels of uremic toxins such as beta2M suppress IFN-gamma production in ESRD patients under low-flux HD. High-flux HD reduces beta2M levels by 30% and improves IFN-gamma production suggesting an improved cellular immune response in ESRD patients.

Diagnostic role of endothelial microparticles in vasculitis.

OBJECTIVE: Endothelial cells play a central pathogenetic role in ANCA-associated small-vessel vasculitis (AAV). Circulating endothelial cells (CECs), as a marker of endothelial damage, have been shown to be elevated in vasculitis. More recently, endothelial microparticles (EMPs) were found to be increased in active childhood vasculitis. The role of EMP in adult AAV and the relationship between EMP and CEC is unclear. PATIENTS AND METHODS: We studied 26 patients with AAV, 12 healthy volunteers and 10 patients with IgA nephropathy as disease control. Platelet-poor plasma was ultracentrifuged. MPs were identified and enumerated with flow cytometry, Annexin V, CD62E and CD105 antibodies. Leucocyte- and platelet-derived MPs were also measured. CEC were isolated and enumerated with CD146-driven immuno-magnetic isolation. RESULTS: EMPs are significantly elevated in patients with active vasculitis (CD62E: mean 248 MP/microl +/- 198 s.d.; CD105: 121 +/- 135/microl) compared with patients in remission/partial remission (CD62E: 55 +/- 30/microl, P = 0.001; CD105: 16 +/- 12/microl, P = 0.002) and healthy volunteers (CD62E: 66 +/- 33/microl, P = 0.002; CD105: 25 +/- 26/microl, P = 0.007). The MP count correlates with disease activity measured by the Birmingham Vasculitis Activity Score (BVAS) (CD62E: r = 0.703; CD105: r = 0.445, P < 0.023). CONCLUSION: EMPs are elevated in active adult AAV. EMP levels correlate with disease activity and might serve as a marker of endothelial activation and damage. Differential detection of endothelial, platelet- and leucocyte-derived MPs may provide more insight in to the pathogenesis of AAV.

Activation of nevi in patients with malignant melanoma.

Activation of melanocytic nevi from patients with malignant melanoma is documented microscopically. Features of activation include marked junctional activity, lack of lateral margination of junctional melanocytic activity, and--to a lesser degree--increased pigment production, inflammation, mitotic activity, and cytologic atypia. The changes are most pronounced in nevi from the same lymph drainage region as the malignant melanoma, suggesting a local activating factor. The presence of marked junctional activity in these lesions and the occurrence of these changes in nevi of patients with clinical Stage I malignant melanomas provide evidence that these lesions do not represent metastases.

Bronchioloalveolar cell carcinoma of the lung: a clinicopathological study.

Thirty-nine patients with bronchioloalveolar carcinoma were reviewed. The primary lung tumor from 27 patients was examined and divided by histological criteria into three categories. The type 1 pattern was associated with a mean survival of 4.7 years. A mean survival of 3.8 years was attained in patients with type 2. Patients with the type 3 pattern had an average survival of 1.4 years. There was a statistically significant difference in survival when types 1 and 2 together were compared with type 3 (rho less than 0.05). Another statistically significant finding was a mean survival of 5.2 years in patients with negative lymph nodes after surgical resection and a 2.2 year mean survival in patients with positive nodes. The tumor histology of bronchioloalveolar carcinoma should be examined carefully to obtain helpful information in predicting survival. We recommend that these tumors be classified as well-differentiated or poorly differentiated bronchioloalveolar carcinoma.

Portal versus systemic transplantation of dispersed neonatal pancreas.

It is not known whether the advantage of the portal vein as a transplant site for islet transplantation is caused by the immediate availability of a blood supply or by the localization of the islets in the portal circulation. We transplanted minimal quantities of islet tissue from neonatal rat donors to isogeneic adult rats with streptozotocin-induced diabetes. Transplants were performed to three sites, i.p., portal vein, and systemic vein (i.v.). When four neonatal donors were used for each recipient there were no i.p. cures but 90% i.v. and 100% portal vein cures, which suggests that access to a blood supply is important. As the amount of tissue transplanted was decreased, there were significantly more cures with the portal vein route, which suggests that localization of the islets in the portal circulation is also important to graft survival.

Ovarian sex cord tumors with annular tubules: an ultrastructural study.

The ultrastructural features of two "sex cord tumors with annular tubules" are presented. The findings are compared with the reported fine structure of ovarian and testicular stromal cells and the cells of gonadal stromal neoplasms. The predominant cell in the "sex cord tumor with annular tubules" has some of the ultrastructural features found in gonadal stromal cells of either ovarian or testicular type; however, no Charcot-Bottcher crystals, lamellar bodies, crystalloids of Reinke, abundant smooth endoplasmic reticulum or complex plasma membrane interdigitations are observed in the tumor cells to suggest wither Sertoli or Leydig cell origin. The striking similarity between the predominant cell type and granulosa cells, as well as the presence of fibrillary material of the type seen in Call-Exner bodies, suggests a granulosa cell origin for these neoplasms. However, the presence of a sparsely distributed second cell type which closely resembles the dark cells in normal nonluteinized ovarian stroma indicates these tumors may arise from the nonspecialized ovarian stroma.

The management of mature teratoma of the testicle.

A case of mature teratoma of the testis, representing the longest documented interval between diagnosis and metastases, is reported. A review of the clinical features, pathology, treatment and survival indicates that mature teratoma is a malignant neoplasm. The need for aggressive treat and long-term followup in patients with this tumor is stressed.

Post-transplant malignant lymphoma. Distinctive morphologic features related to its pathogenesis.

Malignant lymphoma developed in two patients after renal transplantation. In both, the central nervous system was involved. Histologic study of the tumors showed that they were composed of a monomorphous proliferation of cells characterized by a large vesicular nucleus, prominent basophilic nucleolus and strongly pyroninophilic cytoplasm. The tumors thus would be classified as "diffuse large lymphoid lymphomas with pyroninophilia" or "immunoblastic sarcomas" as described in the literature. Tumor cells resembled cells observed in the paracortex of antigenically stimulated lymph nodes, cells from malignant lymphomas in mice that were antigenically stimulated and from malignant lymphomas in patients with immunodeficiency diseases or autoimmune disorders. The distinctive morphologic features of the tumors in the transplant recipients described provide further evidence that long-term antigenic stimulation may be important in their pathogenesis.

Breast adenomas.

True adenomas of the breast are cellular epithelial lesions, which may be confused with carcinoma and are difficult to classify. We have reviewed 28 adenomas of the breast and have developed specific diagnostic criteria, as well as a classification of breast adenomas based on histologic features. Electron microscopic studies confirm that adenomas have ultrastructural features similar to normal breast epithelium and are not variants of fibroadenomas. The association between lactating adenomas and pregnancy has been confirmed; however, clinicopathologic correlation does not suggest a relationship between adenomas and oral hormonal medication. Although adenomas are benign, this study includes the third reported case of an infiltrating carcinoma associated with a lactating adenoma.