High prevalence of antibodies to the 2009 pandemic influenza A(H1N1) virus in the Norwegian population following a major epidemic and a large vaccination campaign in autumn 2009.

The prevalence of antibodies reactive to the 2009 pandemic influenza A(H1N1) was determined in sera collected before the start of the pandemic, during the early phase, and after the main epidemic wave and nationwide vaccination campaign in Norway. A substantial rise in prevalence of antibodies at protective titres, from 3.2% to 44.9%, was observed between August 2009 and January 2010. The highest prevalence, 65.3%, was seen in the age group of 10-19 year-olds.

Empirical tests of Zipf's law mechanism in open source Linux distribution.

Zipf's power law is a ubiquitous empirical regularity found in many systems, thought to result from proportional growth. Here, we establish empirically the usually assumed ingredients of stochastic growth models that have been previously conjectured to be at the origin of Zipf's law. We use exceptionally detailed data on the evolution of open source software projects in Linux distributions, which offer a remarkable example of a growing complex self-organizing adaptive system, exhibiting Zipf's law over four full decades.

High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up.

Human papillomavirus (HPV) causes cervical, vulvar, and vaginal cancers, precancerous dysplasia, and genital warts. We report data for the longest efficacy evaluation to date of a prophylactic HPV vaccine. In total, 552 women (16-23 years) were enrolled in a randomised, placebo-controlled study of a quadrivalent HPV 6/11/16/18 L1 virus-like-particle vaccine with vaccination at months 0, 2, and 6. At regular intervals through 3 years, subjects underwent gynaecologic examination, cervicovaginal sampling for HPV DNA, serum anti-HPV testing, and Pap testing, with follow-up biopsy as indicated. A subset of 241 subjects underwent two further years of follow-up. At 5 years post enrollment, the combined incidence of HPV 6/11/16/18-related persistent infection or disease was reduced in vaccine-recipients by 96% (two cases vaccine versus 46 placebo). There were no cases of HPV 6/11/16/18-related precancerous cervical dysplasia or genital warts in vaccine recipients, and six cases in placebo recipients (efficacy = 100%; 95% CI:12-100%). Through 5 years, vaccine-induced anti-HPV geometric mean titres remained at or above those following natural infection. In conclusion, a prophylactic quadrivalent HPV vaccine was effective through 5 years for prevention of persistent infection and disease caused by HPV 6/11/16/18. This duration supports vaccination of adolescents and young adults, which is expected to greatly reduce the burden of cervical and genital cancers, precancerous dysplasia, and genital warts.

Oral spray immunization may be an alternative to intranasal vaccine delivery to induce systemic antibodies but not nasal mucosal or cellular immunity.

Sixty-five healthy adult volunteers were immunized four times at 1-week intervals with an inactivated whole-virus influenza vaccine based on the strain A/New Caledonia/20/99 (H1N1) without adjuvant. The vaccine was administered as nasal spray with a newly developed device to secure intranasal delivery (OptiMist, OptiNose AS, Oslo, Norway), as regular nasal spray, nasal drops or as an oral spray. Significant IgA-antibody responses in nasal secretions were induced in volunteers immunized intranasally but not after oral spray immunization. In saliva, IgA antibodies were only marginally amplified even after oral spray immunizations. At least 73% of the volunteers belonging to any group of vaccine delivery reached serum haemagglutination inhibition titres of 40 or higher, considered protective against influenza, after only two vaccine doses. Those who had the vaccine delivered intranasally also showed evidence from in vitro secretion of granzyme B that cytotoxic T cells had been stimulated. Although immunization with the breath-actuated OptiMist device and nasal drops were superior with respect to both mucosal and systemic immune responses, oral spray immunization might still be considered for studies of mucosal adjuvants that are not yet acceptable for intranasal use.

Potential human papillomavirus reactivation following topical corticosteroid therapy of genital lichen sclerosus and erosive lichen planus.

Using a highly sensitive polymerase chain reaction (PCR) technique, based on general GP5+/GP6+ PCR primers covering 34 different human papillomavirus (HPV) types, the presence of HPV DNA was studied in paraffin-embedded penile biopsies from 20 men treated topically with corticosteroids. Clobetasol propionate was applied for 2-16 (mean 7) weeks by 19 men (age 18-73; mean 40) with lichen sclerosus. High-risk HPV was detected prior to therapy in three patients (16%) who lacked clinical or histopathological signs of HPV infection. Following therapy high-risk HPV was detected in biopsies from four men (21%), of whom three also exhibited clinical and/or light microscopic signs of HPV infection. Low-risk HPV DNA was not detected in any of these samples. Four biopsies were collected during a 5-year period from a 51-year-old man who was treated repeatedly with topical mild-moderate potent corticosteroids at intervals of up to 10 weeks for penile erosive lichen planus, followed by nine clinical outbreaks of typical condylomas that consistently showed the presence of low-risk HPV DNA only. These observations indicate that long-lasting topical corticosteroid therapy occasionally may be associated with opportunistic reactivation of a latent high- and low-risk mucosotrophic HPV type infection. The importance of clinical follow-up is underlined.

Podophyllin office therapy against condyloma should be abandoned.

Podophyllin, a crude plant extract with low efficacy, high toxicity, and a serious mutagenicity profile does not comply with the WHO guidelines for plant derived treatments and should be removed from clinical treatment protocols. Home treatment with pharmaceutical products based on podophyllotoxin-the purified, standardised active antiwart ingredient of podophyllin-represents safe and effective first line therapy for patients with anogenital warts.

Condyloma eradication: self-therapy with 0.15-0.5% podophyllotoxin versus 20-25% podophyllin preparations--an integrated safety assessment.

Topical application of podophyllin solution, long considered the therapy of first choice against condylomata acuminata, can no longer be recommended due to its low efficacy and gross toxicity. Self-treatment with 0.15-0.5% purified podophyllotoxin preparations, applied twice daily for 3 days, is now advocated as the alternative first-line therapy of choice, when significant improvement is conveniently, and cost-effectively, accomplished within a few weeks. This review provides a summary of the comparative efficacy and utility of podophyllin versus podophyllotoxin as well as a compilation of in vivo and in vitro safety evaluations. In light of overwhelming safety and efficacy data in favor of podophyllotoxin-derived products, it is concluded that podophyllin preparations have no place in the modern treatment portfolio for anogenital warts.

European course on HPV associated pathology: guidelines for primary care physicians for the diagnosis and management of anogenital warts.

The European Course on HPV Associated Pathology (ECHPV) was founded in 1990 by a group of clinicians, pathologists, and virologists to teach important principles for the practice and management of human papillomavirus (HPV) disease to gynaecologists, dermatologists, and other medical disciplines. These guidelines are intended to assist the practice of primary care physicians for diagnosis and treatment of anogenital warts.

Etiology of squamous cell carcinoma of the penis.

OBJECTIVE: To review the epidemiology of invasive cancer of the penis based on scientific publications identified by a Medline search from 1966-2000 for the keywords penis/penile, cancer/carcinoma and risk as well as the cited references in the identified papers. RESULTS: Strong risk factors (OR >10) identified by case-control studies included phimosis, chronic inflammatory conditions such as balanopostitis and lichen sclerosus et atrophicus and treatment with psoralen and ultraviolet A photochemotheraphy (PUVA). A consistent association was found between penile cancer and smoking that was dose-dependent and not explained by investigated confounding factors such as sexual history. Sexual history and self-reported history of condyloma were associated with a 3-5-fold increased penile cancer risk. Cervical cancer in the wife was not consistently associated with cancer of the penis in the husband. Circumcision was associated with penile cancer risk in ecological studies. In a case-control study, circumcision neonatally, but not after the neonatal period, was associated with a 3-fold decreased risk, albeit 20% of penile cancer patients had been circumcised neonatally. In a large number of case series, human papillomavirus (HPV) DNA was identified in penile neoplastic tissue. In penile intraepithelial neoplasia, between 70 and 100% of lesions were HPV DNA positive, whereas invasive penile cancer was positive in only 40-50% of cases. A few serological case-control studies and one prospective study also identified an association between HPV type 16 and penile cancer risk. An association between penile cancer risk and HPV prevalence in the population was also suggested by ecological studies. CONCLUSION: The evidence on risk factors for penile cancer suggests that preventive measures that could be considered include prevention of phimosis, treatment of chronic inflammatory conditions, limiting PUVA treatment, smoking cessation and prophylactic prevention of HPV infection.

Epidemiology of human papillomavirus infection.

Anogenital human papillomavirus (HPV) infection is a sexually transmitted disease (STD) that typically follows a self-limiting transient course for both sexes. The HPV incidences and prevalences vary greatly, because they reflect the sexual activity of the individuals studied and of the population they are in contact with. Higher prevalences are seen in young, sexually active groups and in high-risk areas for cervical and penile cancer, e.g. in Colombia. There has also been an increasing trend with time in Western Europe, paralleling the spread of other STDs and changes in sexual behavior. Penile intraepithelial neoplasia is usually positive for high-risk HPV DNA, mostly of type 16, whereas only approximately 50% of invasive penile cancers are positive for HPV DNA. This is similar to the role of high-risk HPV in vulvar carcinoma, where the attributable proportion is also approximately 40-50%. Moreover, in both sites similar histologic types of squamous cell carcinoma, i.e. the basoloid and basaloid/warty types, are mainly associated with high-risk HPV types. The studies performed so far have indicated that HPV has an etiological role in penile cancer, although the attributable proportion may be only approximately 40-50%.

Diagnosis and clinical presentation of premalignant lesions of the penis.

Although a considerable number of penile cancers may arise de novo, certain potentially premalignant conditions do exist. We account in some detail for precancerous growths, which may initially be misclassified and not submitted to proper therapy and follow-up. At one end of the spectrum disorders exist that are generally considered as medically benign, such as warty tumors; at the other end growths occur that are highly indicative of being potentially invasive, i.e. giant condylomas, bowenoid papulosis, eythroplasia of Queyrat and Bowen's disease. We also focus on elucidating the clinical behavior of some inflammatory conditions, which may either be of pathogenic significance for squamous cell carcinoma development or give rise to differential diagnostic problems, most importantly lichen sclerosus et atrophicus (balanitis xerotica obliterans). We advocate a vigilant approach for histopathological evaluation whenever any clinical diagnostic uncertainty or therapeutic recalcitrance exists. We also favor the administration of highly active topical therapy against penile chronic inflammatory conditions such as lichen sclerosus et atrophicus, careful clinical follow-up of these cases and surgical treatment of phimosis.

Adolescent girls investigated for sexual abuse: history, physical findings and legal outcome.

OBJECTIVE: The aim of the study was to summarize the history of assault and record the results of medicolegal examination in adolescent girls under investigation for alleged sexual abuse, and to monitor the outcome of the legal process. The investigation period was 1990-94. METHOD: A consecutive series of 94 0-para girls, aged 9-22, median age 15.0 years, were examined in the head-to-toe manner including anogenital examination. Girls were referred from investigating police and social authorities. Only non-acute examinations were performed. Findings considered consistent with abusive vaginal penetration were hymenal distortion including deep clefts, hymenal and vestibular scarring, and introital diameter permitting vaginal inspection with a 17 mm speculum in the absence of consensual intercourse. Perianal scarring was recorded. STD sampling was made on indication. Findings were documented on body sketches. Medicolegal conclusions were grouped into three categories according to history and physical findings. Information on the outcome of legal procedures was collected from referring authorities. RESULTS: For 82% (77/94) of the girls, referring agencies provided examining physicians with a detailed and consistent history of abuse, presented results comprise these 77 girls. Intrafamiliar abuse was alleged by 81% (62/77), onset prior to menarche by 53% (41/77), and repeated abuse by 74% (57/77) of the girls. Abusive genital penetration was reported by 77% (59/77) and anal penetration by 19% (14/77). Sequelae after admitted self-inflicted injury were found in 15% (12/77). Deep hymenal clefts and/or vestibular scars were found in 59% (35/59) of the girls reporting penetrative abuse, compared with 6% (1/16) when non-penetrative abuse was alleged, P < 0.001. Girls with experience of voluntary intercourse could all be examined with a 25 mm speculum. Of the 17 girls without experience of consensual intercourse but alleging abusive penetration, 47% (17/36) could easily be examined with a 17 mm speculum, compared to none of 13 reporting non-penetrative abuse, P < 0.001. Non-specific anal abnormalities occurred in 10 (13%) girls; more often when anal abuse was reported, P < 0.001. No specific STDs were found. The medicolegal conclusion supported a history of abusive genital penetration in 41 (69%) cases; findings were non-specific in 11 cases and a normal anogenital status was found in 25 cases. The alleged abuse of 34 of the 77 (44%) girls was tried in court. One suspect was acquitted, 32 men were convicted of the abuse of 33 girls. Eleven perpetrators admitted abuse, and their histories were in concordance with the abuse alleged by the victims, as well as with the physical findings. CONCLUSION: A medicolegal diagnosis of alleged non-acute cases of sexual abuse relies on a detailed history. Adolescent girls alleging abuse may exhibit signs of admittedly self-inflicted extragenital injury. Our findings confirm that non-penetrative sexual acts leave no lasting genital signs, but that repeated abusive genital penetration significantly more often than non-penetrative abuse leaves deep posterior hymenal clefts and/or vestibular scarring, and a hymenal opening allowing examination with 17-25 mm specula also in girls without experience of voluntary intercourse. In cases with a confessing perpetrator, no discordance was found between the history of the victim, medicolegal conclusion and the history of the perpetrator.

Penile lichen sclerosus et atrophicus treated with clobetasol dipropionate 0.05% cream: a retrospective clinical and histopathological study.

BACKGROUND: Treatment with clobetasol propionate 0.05% cream is effective against lichen sclerosus et atrophicus (LSA) of the vulva. OBJECTIVE: The purpose of this study was to retrospectively evaluate whether clinical and histologic responses to topical clobetasol can be accomplished in penile LSA. METHODS: A self-assessment questionnaire was obtained from 22 men with LSA, and a clinical examination was performed in 21 of them. Biopsy specimens from 15 cases were compared before and after treatment. RESULTS: Itching, burning, pain, dyspareunia, phimosis, and dysuria decreased significantly (P < .001 to .05) after 1 to 2 daily applications, for a mean of 7.1 weeks (2-16 weeks). Additional operation for phimosis was required in 6 of the 22 men. All histologic LSA criteria were significantly (P < .01 to .05) reduced after treatment. CONCLUSION: Topical treatment of penile LSA with clobetasol propionate represents a safe and effective therapy with no risk of epidermal atrophy but with some potential for triggering latent infections, most importantly human papillomavirus.

Efficacy of surgical and/or podophyllotoxin treatment against flat acetowhite penile human papillomavirus associated lesions.

In order to investigate the efficacy of treatment modalities favoured by us against flat acetowhite penile human papillomavirus (HPV)-induced lesions, we studied retrospectively standardized medical records of 81 men who had been treated for this condition. The patients were treated surgically with diathermy (n=32) or with a combination of both chemical (topical application of podophyllotoxin) and surgical treatment (n=49). The mean number of clinic visits was 9.1 (range 1-19), during a follow-up time of mean 30.9 (range 1-104) months for 78 of the men, 3 of them only visited the clinic once. The mean time for cure was 19.9 (range 0-103) months. Only 12 (15%) patients were healed after one single treatment session, while as many as 50 (62%) required > 4 sessions. The mean number of surgical treatment sessions required for cure differed significantly (P=0.0006) between the previously treated patients who needed a mean of 5.6 treatment sessions, compared to the previously untreated men who required surgery a mean of 3.4 times for cure.

Potential public health benefits from testing with Chlamydia trachomatis PCR technique on first void urine in men.

Urine samples from 467 men living in the Stockholm area were tested with the polymerase chain reaction (PCR), Roche Amplicor, and with an enzyme-linked immunosorbent assay, Syva MicroTrak EIA, for detection of Chlamydia trachomatis. The predictive value of urine versus urethral samples was subsequently compared on a second urethral sample from 25 C. trachomatis-positive cases. The urethral samples were in addition cultured for C. trachomatis. C. trachomatis was found more often in urine by Roche Amplicor than by Syva MicroTrak, 9.9% and 7.9%, respectively. Nine urine samples, positive only by Amplicor, could be confirmed as true positives by complementary testing. C. trachomatis was detected with the same frequency in urine and urethral samples. The sensitivity was highest for PCR, 88% and 92%, and lowest for EIA, 76% and 80%, on urethral and urine samples, respectively. Urine sampling, offering a non-invasive procedure, was found suitable for the diagnosis of C. trachomatis in men, with the use of Roche Amplicor.