Smoking and genital human papilloma virus infection in women attending cervical cancer screening in Greece

AIM: To investigate whether smoking is associated with human papilloma virus (HPV) infection. METHODS: HPV infection is considered to be a necessary condition for cervical cancer development. The study population included 1291 women, aged 25-55 years, attending cervical cancer screening. All women had a Papanicolaou (Pap) test, with liquid-based cytology (Thinprep^®), an HPV-DNA test and an evaluation of smoking habits. The COBAS^® 4800 system was used for HPV-DNA testing, enabling identification of the following high-risk HPV (hrHPV)-types: each of HPVs 16 and 18 separately, and HPVs 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 as a cocktail. The evaluation of smoking habits was assessed using the smoking intensity index (SII), a variable formed as the product of cigarettes consumed per day by the days (years × 365) that a woman was a smoker, divided by 1000. RESULTS: There were 136 smokers among 238 women tested positive for hrHPV-types (HPVs 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and/or 68), and 463 smokers among 1053 hrHPV-negative women (OR = 1.7, P < 0.001). This association was attributed to the youngest age group of women, aged 25-34 years (OR = 2.3, P < 0.001), while there was no association in other age groups. The intensity of smoking (increasing SII) showed no statistically significant association with hrHPV infection. Cervical infection with HPV 16 and/or HPV 18 was also not associated with age or smoking habits. Finally, no association was found between Pap test status and smoking habits or smoking intensity. CONCLUSION: Smoking appears to be associated with hrHPV infection of the uterine cervix, particularly in younger women. Further studies should investigate whether this association is based on causality and evaluate the role of other possible co-factors.     

Metastatic neoplasms of the ovaries: a clinicopathological study of 97 cases

Objective  

To present the clinicopathological features of metastatic ovarian neoplasms with emphasis in the diagnostic challenge.     

Investigation of the genotoxic effect of pesticides on greenhouse workers' lymphocytes

In the present study, the genotoxic effects of commonly applied pesticides were evaluated using the alkaline comet assay (pH > 13). The amount of DNA damage (% DNA in tail) in peripheral lymphocytes of 49 male agricultural workers from Southern Poland were measured and compared to 50 men from the same area who had no previous occupational exposure to pesticides. No statistically significant differences in basal DNA damage were found between the study groups. In addition, exposure of peripheral blood lymphocytes to hydrogen peroxide (100 and 150 μM) or γ‐irradiation (2.5 or 4.2 Gy) led to a similar degree of additional DNA damage and subsequent repair (for 2 hr) for all studied populations. In conclusion, our results indicate that the greenhouse workers who participated in this study had no detectable increased DNA damage or alteration in their cellular response to DNA damage in comparison to our control population. Environ. Mol. Mutagen., 2009. © 2008 Wiley‐Liss, Inc.     

Novel mutation of the PRNP gene of a clinical CJD case

Background  

Transmissible spongiform encephalopathies (TSEs), a group of neurodegenerative diseases, are thought to be caused by an abnormal isoform of a naturally occurring protein known as cellular prion protein, PrP^C. The abnormal form of prion protein, PrP^Sc accumulates in the brain of affected individuals. Both isoforms are encoded by the same prion protein gene (PRNP), and the structural changes occur post-translationally. Certain mutations in the PRNP gene result in genetic TSEs or increased susceptibility to TSEs.     

Regulation of myeloperoxidase‐specific T cell responses during disease remission in antineutrophil cytoplasmic antibody–associated vasculitis: The role of Treg cells and tryptophan degradation

Objective

T lymphocytes have been implicated in the pathogenesis of antineutrophil cytoplasmic antibody–associated vasculitis (AAV). Patients with myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA) experience relapses less frequently than those with proteinase 3 ANCA, suggesting greater immune regulation. This study was undertaken to investigate MPO‐specific T cell reactivity during disease remission and the factors regulating their responsiveness.

Methods

MPO‐specific T cells were quantified by enzyme‐linked immunospot assay with additional Treg cell depletion or exogenous interleukin‐2. Serum tryptophan and its metabolites were measured. In vivo blockade of indoleamine 2,3‐dioxygenase (IDO) was performed, and its effect on MPO reactivity was assessed.

Results

During disease remission, MPO‐specific interferon‐γ–producing T cell frequencies were comparable with those found in healthy controls and significantly lower than those found in patients with acute disease. CD4+CD25+ regulatory cells did not play a role in maintaining these low MPO‐specific T cell frequencies, since depletion of Treg cells did not augment MPO‐specific responses, and FoxP3 levels were diminished in patients compared with controls. Treg cell function, however, was comparable in patients and controls, suggesting numerical rather than functional deficiency. We found diminished serum tryptophan levels and elevated levels of its metabolite kynurenine in patients with MPO AAV as compared with controls. To confirm the effect of tryptophan degradation on MPO responses in vivo, we inhibited degradation in MPO‐immunized WKY rats and found greater immune responsiveness to MPO and a tendency to more severe glomerulonephritis.

Conclusion

Our findings indicate that MPO‐specific T cell frequencies are regulated during disease remission in association with tryptophan degradation. The tryptophan regulatory pathway is induced during active disease and persists during disease remission.

     

Maternal health outcomes among HIV-infected breastfeeding women with high CD4 counts: results of a treatment strategy trial

Background: IMPAACT PROMISE 1077BF/FF was a randomized study of antiretroviral therapy (ART) strategies for pregnant and postpartum women with high CD4+ T-cell counts. We describe postpartum outcomes for women in the study who were randomized to continue or discontinue ART after delivery.

Methods: Women with pre-ART CD4+ cell counts ≥350 cells/mm³ who started ART during pregnancy were randomized postpartum to continue or discontinue treatment. Women were enrolled from India, Malawi, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe. The primary outcome was a composite of progression to AIDS-defining illness or death. Log-rank tests and Cox regression models assessed treatment effects. Incidence rates were calculated per 100 person-years. A post hoc analysis evaluated WHO Stage 2/3 events. All analyses were intent-to-treat.

Findings: 1611 women were enrolled (June 2011–October 2014) and 95% were breastfeeding. Median age at entry was 27 years, CD4+ count 728 cells/mm³ and the majority of women were Black African (97%). After a median follow-up of 1.6 years, progression to AIDS-defining illness or death was rare and there was no significant difference between arms (HR: 0·55; 95%CI 0·14, 2·08, p?=?0.37). WHO Stage 2/3 events were reduced with continued ART (HR: 0·60; 95%CI 0·39, 0·90, p?=?0.01). The arms did not differ with respect to the rate of grade 2, 3, or 4 safety events (p?=?0.61).

Interpretation: Serious clinical events were rare among predominately breastfeeding women with high CD4+ cell counts over 18 months after delivery. ART had significant benefit in reducing WHO 2/3 events in this population.     

Variable behavior and complications of autologous bone marrow mesenchymal stem cells transplanted in experimental autoimmune encephalomyelitis

Autologous bone marrow stromal cells (BMSCs) offer significant practical advantages for potential clinical applications in multiple sclerosis (MS). Based on recent experimental data, a number of clinical trials have been designed for the intravenous (IV) and/or intrathecal (ITH) administration of BMSCs in MS patients. Delivery of BMSCs in the cerebrospinal fluid via intracerebroventricular (ICV) transplantation is a useful tool to identify mechanisms underlying the migration and function of these cells. In the current study, BMSCs were ICV administered in severe and mild EAE, as well as naive animals; neural precursor cells (NPCs) served as cellular controls. Our data indicated that ICV-transplanted BMSCs significantly ameliorated mild though not severe EAE. Moreover, BMSCs exerted significant anti-inflammatory effect on spinal cord with concomitant reduced axonopathy only in the mild EAE model. BMSCs migrated into the brain parenchyma and, depending on their cellular density, within brain parenchyma formed cellular masses characterized by focal inflammation, demyelination, axonal loss and increased collagen-fibronectin deposition. These masses were present in 64% of ICV BMASC-transplanted severe EAE animals whereas neither BMSCs transplanted in mild EAE cases nor the NPCs exhibited similar behavior. BMSCs possibly exerted their fibrogenic effect via both paracrine and autocrine manner, at least partly due to up-regulation of connective tissue growth factor (CTGF) under the trigger of TGFb1. Our findings are of substantial relevance for clinical trials in MS, particularly regarding the possibility that ICV transplanted BMSCs entering the inflamed central nervous system may exhibit – under conditions – a local pathology of yet unknown consequences.     

Surgical revision of complicated false and true vascular access-related aneurysms

PURPOSE: This prospective observational study examined the effect of revision surgery in patients who present solely with complicated arteriovenous access (AVA)-related aneurysms. METHODS: The demographics and comorbid conditions of 44 hemodialysis access patients who presented with complicated true or false AVA-related aneurysms and underwent revision surgery during a 7-year period were prospectively entered into our AVA database. Also recorded were AVA characteristics before and after revision. Arteriovenous access anatomy was evaluated preoperatively using color Doppler ultrasonography, and AVA adequacy was assessed in all patients postoperatively after the first needle puncture and every month thereafter. Postintervention access function and primary patency rates were analyzed. Patency was evaluated using the Kaplan-Meier method and compared between groups of patients with different AVA characteristics before and after revision using the log-rank test. RESULTS: The cases of initial AVA with complicated aneurysms comprised 16 radiocephalic, 8 brachiocephalic, 2 basilic vein transposition, and 18 prosthetic fistulas (7 and 11 of the lower and upper arm, respectively), of which 42 were dysfunctional and 2 had thrombosed early at presentation. Primary indications for revision were danger of aneurysm rupture in 26, duplication in graft aneurysm diameter in 18, painful aneurysm in 12, stenosis due to partial aneurysm thrombosis in 12, shortness of the potential cannulation area in 12, aneurysm enlargement in 4, infected aneurysm in 2, and completely thrombosed aneurysm in 2. The mean postintervention primary patencies were 93%, 82%, 57%, and 32% at 3, 6, 12, and 24 months, respectively. The outcomes was better in autogenous than prosthetic corrections, in true than false aneurysms, in patients with two or fewer than more than 2 previous AVAs on revised arms, and in forearm than upper-arm corrections (P = .0197, P = .004, P = .0022, and P = .0225, respectively). CONCLUSIONS: Surgical revision of complicated false and true AVA-related aneurysms reveals acceptable postintervention primary patency rates and therefore is justified. This outcome measure was superior in the following specific groups of corrections: autogenous were better than prosthetic, true aneurysms were better than false aneurysms, patients with one or two previous AVAs in the revised arm were better than those with more than two previous accesses in the revised arm, and finally, forearms were better than those in the upper arm.