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.

Macrolides for the treatment of chronic bacterial prostatitis: an effective application of their unique pharmacokinetic and pharmacodynamic profile (Review).

Chronic bacterial prostatitis (CBP) is a persistent infection of the prostate characterized by poor quality of life mainly due to frequent relapse episodes caused by incomplete eradication of causative pathogens. Aggressive antibacterial therapy is required to attenuate the severe symptoms of CBP and to achieve a permanent cure. Although fluoroquinolones are currently recommended as first-choice agents, macrolide antibiotics are emerging as a noteworthy option for the treatment of CBP. Macrolide antibiotics are characterized by an impressive array of distinct pharmacokinetic (PK) and pharmacodynamic (PD) properties. These properties include high intracellular accumulation in phagocytes and at sites of infection, including the prostate; broad antibiotic but also biofilm-inhibiting properties; immunomodulating and inflammation-resolving activities. These features offer particular advantages for the treatment of chronic infections of the prostate gland, which are not easily amenable to drug therapy. Macrolides may be exploited to counteract the unsatisfactory rates of clinical symptom improvement and pathogen eradication. The results of a number of clinical trials support this proposal.

Clinical and microbiological efficacy of prulifloxacin for the treatment of chronic bacterial prostatitis due to Chlamydia trachomatis infection: results from a prospective, randomized and open-label study.

The purpose of this study was to compare the efficacy of a 14-day course of prulifloxacin 600 mg with standard antibiotic therapy for the treatment of chronic prostatitis due to Chlamydia trachomatis (Ct) infection. All patients with clinical and instrumental diagnosis of bacterial chronic prostatitis (CP) due to Ct infection were enrolled. After randomization, all patients were administered oral prulifloxacin 600 mg once daily for 14 days or doxycycline 100 mg orally twice daily for 21 days. At enrollment and 30 days after beginning treatment, all patients underwent microbiological cultures for uropathogens bacteria and yeasts, DNA extraction and mucosal IgA evaluation for Ct diagnosis, seminal plasma IL-8 evaluation and serum IgA and IgG anti-Ct analysis. The National Institutes of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) was given to each patient. A total of 109 patients received prulifloxacin and 102 received standard therapy. Prulifloxacin had clinical efficacy rates equivalent to standard therapy (82.5% vs. 79.9%) (P = 0.08) and showed superior microbiological efficacy rates compared to standard therapy, in terms of decreasing mucosal IgA (P < 0.001) and IL-8 levels (P < 0.001). Prulifloxacin was also equivalent to standard therapy for clinical success, as demonstrated by a decrease in the number of patients affected by CP due to Ct infection.

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.

Human immunodeficiency virus (HIV)-specific IgA and HIV neutralizing activity in the serum of exposed seronegative partners of HIV-seropositive persons.

The presence and activity of human immunodeficiency virus (HIV)-specific antibodies were analyzed in the sera of 15 sexually exposed seronegative persons who had systemic HIV-specific cell-mediated immunity and IgA-mediated mucosal immunity and in their HIV-infected partners. The HIV-positive subjects had HIV-specific serum IgG and IgA; the seronegative persons had HIV-specific serum IgA in the absence of IgG. Testing of the seronegative persons 1 year after the interruption of at-risk sex showed that no IgG seroconversion had occurred and that HIV-specific IgA serum concentrations had declined. Serum from the HIV-exposed seronegative persons was analyzed for the ability to neutralize primary HIV-1 isolates. Neutralizing activity was detected in 5 of 15 sera and in 2 cases was retained by serum-purified IgA. Thus, the immunologic picture for resistance to HIV infection should include HIV-specific cell-mediated immunity as well as HIV-specific IgA-mediated mucosal and systemic immunity.

A role for mucosal immunity in resistance to HIV infection.

In a recent, thought-provoking novel by Elizabeth McCracken (The Giant's House. Avon Books, New York, 1997), two characters discuss love and its impossibilities. One brashly claims to be "immune to love", explaining the concept to his perplexed interlocutor, "...people become immune to love like they become immune to any disease. Either they had it bad early in life, like chicken pox and that's that; or they keep getting exposed to it in little doses and build up an immunity; or somehow they just don't catch it, something in'em is born resistant. I'm the last type. I'm immune to love and poison ivy". (p. 275) (E. McCracken, The Giant's House. Avon Books, New York, 1997). Substitute the words 'HIV infection' for 'love' and this intriguing metaphor summarizes the state of the art working hypotheses for the phenomenon of resistance to HIV infection in HIV-exposed individuals who, against all odds, do not seroconvert. These hypotheses will be discussed hereafter and particular emphasis will be placed upon a possible role for mucosal immunity in this phenomenon.

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.

[Adolescent sexual behavior and sexually transmitted diseases (STD). A preliminary study]. / II comportamento sessuale dell'adolescente e le malattie sessualmente trasmesse (MST). Indagine preliminare.

Great changes have occurred in the adolescent behaviour in the last twenty years; this has caused a great increase in the number of the transmitted by sexual intercourse diseases. These, along with the adolescent habits changing, have so widely spread among young people, that one third of the recorded case are actually referred to this group of age. So, a matter of great social interest, which would require a common effort by the adolescents' families, the teachers and by the adolescents themselves, to be faced in the most proper way, has arisen. But the greatest commitment is asked for to the specialized in infectious diseases pediatricians, who are called to state the best strategy to efficaciously fight adolescents' STD. Pediatricians' specific competence and experience can build up the major security to face the prevention and diagnostic matters and their therapy as well.

[Infections due to central catheterizations in a cardiac intensive care unit: an evaluation of 6 months of continuous surveillance. The nursing personnel of a cardiac intensive care unit]. / Infezioni da cateterismi centrali in UTIC: valutazione di sei mesi di sorveglianza continua. Personale infermieristico UTIC.

BACKGROUND: Infections in intensive care unit are nowadays well documented. As no recent papers about catheter related infections in cardiological intensive care units were found, we decided to approach them during a period of six months with a surveillance study including a clinical, nursing and microbiological protocol. METHODS: The microbiological protocol the semiquantitative Maki cultural evaluation of the tips, the interior of the hubs and the skin around the catheter insertion point. In addition, all the samples were additionally cultured in liquid media. A total of 432 biological samples were analysed, from 125 patients entered into our cardiological intensive care unit: 144 from catheter tips, 144 from the hubs and 144 from the skin around the catheter insertion. RESULTS: Three hundred and eighty-four biological samples (88.9%) were completely negative. Thirteen tips resulted positive (27.1% of the 48 total positive biological samples): 92.3% (12/13) of the positive catheters were infected from internal origin, hub and skin resulting culture negative. Of the 144 catheter tips 12 were colonized (C.F.U. < 15) while only 2 resulted infected (C.F.U. > or = 15). Only one patient was infected with an exogenous infection presenting tip, hub and skin positivity. The overall positivity was of 214 microorganisms mainly represented (93.5%) by gram positives; 87% of them were coagulase-negative staphylococci (C.N.S.). In addition, the tip detection of a Candida guillermondii strain in a pacemaker patient is a relevant finding. CONCLUSIONS: The very low number of cutaneous contaminations (1.3%) and patient's infections (0.69%) showed the good sensibilisation of the medical and nursing teams in the infection control and surveillance.

[Guideline for the prevention of sexually transmitted diseases in adolescents (University of Florence, Pediatric Department)]. / Linee guida per la prevenzione delle malattie sessualmente trasmesse (MST) nell'adolescente.

Adolescent had in the past rarely been affected by sexually transmitted infections. Nowadays they must be considered possibly running such risks as they begin their sexual activity earlier or do not know enough about these kinds of troubles. Therefore a valid primary prevention is necessary based upon correct information.

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.