Natural history of human papillomavirus infection in non-vaccinated young males: low clearance probability in high-risk genotypes.

In this study, we aimed to investigate the clearance of type-specific genital human papillomavirus (HPV) infection in heterosexual, non-HPV-vaccinated males whose female partners were positive to HPV DNA tests. All consecutive men attending the same sexually transmitted diseases (STD) centre between January 2005 and December 2006 were considered for this study. All subjects (n = 1009) underwent a urologic visit and microbiological tests on first void, midstream urine and total ejaculate samples. One hundred and five patients were positive for HPV DNA (10.4 %; mean age: 34.8 ± 5.8 years) and consented to clinical examination and molecular diagnostic assays for HPV detection scheduled every 6 months (median surveillance period of 53.2 months). HPV genotypes were classified as high risk, probable high risk and low risk. HPV-positive samples which did not hybridise with any of the type-specific probes were referred to as positive non-genotypeable. At enrollment, the distribution of HPV genotypes was as follows: high-risk HPV (n = 37), probable high-risk HPV (n = 6), low-risk HPV (n = 23) and non-genotypeable HPV (n = 39). A high HPV genotype concordance between stable sexual partners emerged (kappa = 0.92; p < 0.001). At the end of the study, 71/105 (67.6 %) subjects were negative for HPV (mean virus clearance time: 24.3 months). With regard to the HPV genotype, virus clearance was observed in 14/37 (37.8 %) high-risk HPV cases, 6/6 (100 %) probable high-risk HPV cases, 20/23 (86.9 %) low-risk HPV cases and 31/39 (79.5 %) non-genotypeable cases. The high-risk HPV genotypes showed the lowest rate and probability of viral clearance (p < 0.001). In our series, high-risk HPV infections were more likely to persist over time when compared with other HPV genotypes.

14-day prulifloxacin treatment of acute uncomplicated cystitis in women with recurrent urinary tract infections: a prospective, open-label, pilot trial with 6-month follow-up.

Recurrent urinary tract infections (UTI) are very common in otherwise healthy young women, and can have a very negative social and economic impact. In order to evaluate the tolerability and efficacy of a 14-day course of prulifloxacin orally administered once daily, 51 young female patients, attending the same STD center between may and June 2007 for symptoms of cystitis, with a history of recurrent UTI and urine culture positive for uropathogens, were enrolled in this prospective study. Microbiological and clinical efficacy was tested over three follow-up visits at 1, 3 and 6 months. Quality of life (QoL) was measured and the impact of prulifloxacin in modifying the Lactobacillus vaginal flora was also evaluated. At baseline, the pathogens most commonly isolated were Enterococcus faecalis (43.2%) and Escherichia coli (27.5%). 41 of the 51 women, (80.3%) had Lactobacillus spp. in vaginal samples at baseline. microbiological results at follow-up examinations were as follows: after 1 month, 47 patients were recurrence-free and 4 had recurrence; after 3 months, 41 were recurrence-free, while 6 reported recurrence; finally, after 6 months, 36 were recurrence-free and 5 had recurrence. A statistically significant difference was reported between the QoL questionnaire mean scores at baseline (0.63), 1 (0.77), 3 (0.77) and 6 months (0.78) after treatment (all p<0.001). the vaginal swab cultures demonstrated that Lactobacillus spp. flora was maintained in 38 out of the 41 (92.6%) patients who had positive vaginal swab sample at baseline. in conclusion, a 14-day administration of prulifloxacin 600 mg is a safe, well tolerated and effective treatment for the management of UTI in young women.

Serum imbalance of cytokines in melanoma patients.

The cytokines interleukin (IL)6 and IL10 appear to be involved in the progression of melanoma because they are secreted by malignant cells and their serum levels are associated with poor survival and with advanced stages of the disease. Antitumour immunity is considered to be a T-cell response, mediated mainly by type 1 cytokines such as IL12 and interferon-gamma (IFNgamma). We evaluated the serum levels of cytokines involved in the host response against tumour (IL12, IFNgamma) and/or the progression of melanoma (IL6, IL10) in 45 melanoma patients with localized and metastatic disease and in 45 controls, using commercially available enzyme-linked immunosorbent assay (ELISA) kits. In the controls, IL6 and IL12 were nearly undetectable, whereas the IL10 and IFNgamma ranges were 0.5-9 pg/ml and 2-4.8 pg/ml, respectively. In the melanoma patients, pathologically high values were found in 44.4% for IL6, in 24.4% for IL10, and in 60% for IL12. Significantly higher values were found for IL6 and IL12, and lower values for IFNgamma. This study highlights a significant difference in serum cytokine profiles between controls and melanoma patients, which is mainly due to the high levels of IL6 and IL12 and the low levels of IFNgamma.

Immunohistochemical evidence of cytokine networks during progression of human melanocytic lesions.

Melanoma cells in culture express a variety of growth factors and cytokines and some of their autocrine and paracrine roles have been investigated. However, less information is available on the potential dynamic changes in expression of these molecules on cells during melanoma development and progression in situ. Using immunohistochemistry, we tested 40 nevi and primary and metastatic melanoma lesions for the expression of 10 growth factors and cytokines and the respective receptors representing 10 cell surface molecules. Nevi and thin (< 1 mm) primary melanomas showed little expression of ligands except weak reactivity of tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), interleukin-8 (IL-8) and reactivity of TGF-betaR and c-kit. Marked up-regulation of growth factors, cytokines and receptor expression was observed in thick (> 1 mm) primary melanomas, which were stained with polyclonal or monoclonal antibodies (MAbs) for IL-1alpha, IL-1beta, IL-6, IL-8, TNF-alpha, TGF-beta, granulocyte-macrophage colony-stimulating factor (GMCSF) and stem cell factor (SCF), but not IL-2. Metastases showed similar expression patterns except that SCF was absent. Co-expression of ligand and receptor was observed for TGF-beta, GM-CSF and IL-6, suggesting an autocrine role for these ligands. TNF-alpha appears to be a marker of benign lesions; IL-6 and IL-8 expression is associated with biologically early malignancy; TGF-beta, GM-CSF and IL-1alpha are highly expressed in biologically late lesions; and TNF-beta is an apparent marker of metastatic dissemination. Our results indicate that melanoma cells utilize cascades of growth factors and cytokines for their progression.

Chlamydia pneumoniae antibody response in patients with acute myocardial infarction and their follow-up.

STUDY POPULATIONS: This study concerned the possible relations between seroreactivity to Chlamydia pneumoniae and myocardial infarction. A group of 29 patients with acute myocardial infarction (AMI), 74 members of a healthy control group, and a subgroup of 24 members of a healthy control group matched for age, sex, and coronary risk factors (HCM) were included in the study. In addition, we evaluated the AMI group in a 1-year patients' follow-up study. We used two different tests to detect anti-C. pneumoniae antibodies: recombinant enzyme immunoassay antilipopolysaccharide antibodies and a reference microimmunofluorescence test. RESULTS: High titers of C. pneumoniae microimmunofluorescence antibodies were found in 89.65% of the AMI group and in 25% of the HCM group (p = 0.0000065). Immunoglobulin A-microimmunofluorescence was 51.72% in the AMI group and 20.83% in the HCM group (p = 0.0042). Immunoglobulin G and immunoglobulin A antilipopolysoccharide titers were 65.51% and 62.60% in the AMI group and 20.83% in the HCM group, respectively (p = 0.006). High concentrations of interleukin-6 were found in 86.20% of our AMI group (p value = 54.38 pg/ml) when compared with the control group. A good correlation between interleukin-6 levels and immunoglobulin A-lipopolysaccharide titers (r = 0.658) was found. CONCLUSION: The presence of a high prevalence rate and high titers of immunoglobulin G and immunoglobulin A-specific anti-C. pneumoniae antibodies in AMI at admission demonstrated the presence of a specific anti-C. pneumoniae immunization in the AMI population.

HIV-specific mucosal and cellular immunity in HIV-seronegative partners of HIV-seropositive individuals.

HIV-specific mucosal and cellular immunity was analyzed in heterosexual couples discordant for HIV status in serum and in HIV-unexposed controls. HIV-specific IgA but not IgG was present in urine and vaginal wash samples from HIV-exposed seronegative individuals (ESN), whereas both IgA and IgG were observed in their HIV-seropositive partners; antibodies were not detected in low-risk controls. Envelope protein (Env) peptide-stimulated interleukin-2 (IL-2) production by peripheral blood mononuclear cells (PBMCs) was detected in 9 out of 16 ESNs, 5 out of 16 HIV-infected patients and 1 out of 50 controls. Env peptide-stimulated PBMCs of ESNs produced more IL-2 and less IL-10 compared with those of HIV-infected individuals; no differences were observed in chemokine production or in CCR5 expression. These data demonstrate that a compartmentalized immune response to pathogens is possible in humans and raise the possibility of protective roles for cell-mediated immunity and mucosal IgA in HIV-seronegative individuals exposed to HIV.

[Anti-Chlamydia pneumoniae antibodies and production of interleukin 6 in acute myocardial infarct]. / Anticorpi anti Chlamydia pneumoniae e produzione di interleuchina 6 nell'infarto miocardico acuto.

UNLABELLED: Chlamydia pneumoniae (C.p.) has been correlated with acute myocardial infarction (AMI). High levels of anti-C.p. antibodies and circulating immune complexes containing C.p. lypopolyaaccharide (LPS) antigens have been demonstrated in AMI. LPS antigen and especially Chlamydial LPS is one of the best antigen and it is also a very good Interleukin inductor. Moreover, interleukin 6 (IL-6) has been observed in AMI patients. The aim of our study was to assess the possible relationships between anti-C.p. immune response and IL-6 production in AMI patients. We studied 17 consecutive patients with myocardial infarction (12 males and 5 females; mean age 62; range 46-72). Blood samples were obtained immediately after hospital admission. There were 17 control subjects (HCM) (mean age 62; range 45-72) who were matched for the main coronary risk factors (gender, age, diabetes, hypertension, hypercolesterolemia, smoking, family history of ischemic heart disease). In addition, we evaluated the AMI patients in a one-year follow-up study (FU). RESULTS: High levels of C.p. IgG MIF were found in 82.3% of our AMI patients and in 29.4% of HCM subjects (p = 0.0000065). IgA-MIF were 70.5% in AMI patients and 29.4% in HCM (p = 0.0042). High levels of C.p. IgG and IgA anti-LPS were found, with a very high prevalence rate of 76.4% and 64.7% in AMI patients, and both rates were 47.0% (p = 0.158; p = 0.489) in HCM. Very high levels of IL-6 were found (m = 54.38 pg/ml) in 100% of the AMI patients (normal values in our population: 0-10.86 pg/ml) and only detectable levels in 5.8% of HCM. A good linear correlation was demonstrated between IL-6 and IgA levels in the first sample (r = 0.655). The high levels of anti-C.p. IgG, IgA and IL-6, with a good correlation between IL-6 and IgA levels, may confirm the presence of an active infection and probably of a reinfection.

Exposure to carcinogenic chemicals and smoking increases urinary excretion of mutagens in humans.

Urine samples from a control population and from a population of chemical workers from two chemical plants near Florence, Italy, were analyzed for the presence of mutagenic chemicals by the Salmonella/microsome test. When tested with strain TA1538, the urine of nonsmoking chemical workers showed higher mutagenic activity than that of controls in the presence of in vitro metabolic activation, but no difference was found between controls and chemical workers who both smoked. Increased mutagenic activity was observed in the group of control smokers compared to control nonsmokers, but the same effect was not observed for chemical workers. When TA100 was used as the tester strain, the chemical workers, both smoking and nonsmoking, had significantly higher mutagenic activity than controls. The mutagenic activity fell to control levels in some workers' urine after 20 d leave. Although some perturbing effects of smoking habits were observed, the results seemed to indicate the usefulness of the Salmonella/microsome test for detection of mutagens in human urine. The results also suggest that people exposed to potentially carcinogenic chemicals may show high enough traces of those chemicals and/or their metabolites in their body fluids to be detected with current mutagenesis techniques.