Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial

Objectives: To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata). Design: Data from two international, double blind, placebo controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013 (FUTURE I) and protocol 015 (FUTURE II)). The trials were to be 4 years in length, and the results reported are from final study data of 42 months' follow-up. Setting: Primary care centres and university or hospital associated health centres in 24 countries and territories around the world. Participants: 17 622 women aged 16-26 years enrolled between December 2001 and May 2003. Major exclusion criteria were lifetime number of sexual partners (>4), history of abnormal cervical smear test results, and pregnancy. Intervention: Three doses of quadrivalent HPV vaccine (for serotypes 6, 11, 16, and 18) or placebo at day 1, month 2, and month 6. Main outcome measures: Vaccine efficacy against cervical, vulvar, and vaginal intraepithelial neoplasia grade I and condyloma in a per protocol susceptible population that included subjects who received all three vaccine doses, tested negative for the relevant vaccine HPV types at day 1 and remained negative through month 7, and had no major protocol violations. Intention to treat, generally HPV naive, and unrestricted susceptible populations were also studied. Results: In the per protocol susceptible population, vaccine efficacy against lesions related to the HPV types in the vaccine was 96% for cervical intraepithelial neoplasia grade I (95% confidence interval 91% to 98%), 100% for both vulvar and vaginal intraepithelial neoplasia grade I (95% CIs 74% to 100%, 64% to 100% respectively), and 99% for condyloma (96% to 100%). Vaccine efficacy against any lesion (regardless of HPV type) in the generally naive population was 30% (17% to 41%), 75% (22% to 94%), and 48% (10% to 71%) for cervical, vulvar, and vaginal intraepithelial neoplasia grade I, respectively, and 83% (74% to 89%) for condyloma. Conclusions: Quadrivalent HPV vaccine provided sustained protection against low grade lesions attributable to vaccine HPV types (6, 11, 16, and 18) and a substantial reduction in the burden of these diseases through 42 months of follow-up. Trial registrations: NCT00092521 and NCT00092534.

Vulvar carcinoma in young patients and its relationship with genital warts

We report the occurrence of aggressive vulvar carcinoma associated with condyloma acuminata in three patients: under 33 years old. Discussion of the role of the human papilloma virus (HPV) in the development of vulvar cancer is also presented. Three patients with condyloma associated with aggressive vulvar squamous cell carcinoma, in situ (1 case) and invasive (2 cases), documented by biopsy and/or vulvectomy are presented. In situ hybridization (ISH) was used to characterize the subtypes of HPV. One patient with erythematous systemic lupus developed in situ carcinoma after 5 years. The other two cases also developed aggressive multicentric, invasive squamous cell carcinoma after 10 years of diagnosis of condyloma. In all cases HPV cytological abnormalities were seen throughout the pathological examination. HPV 16 and 18 were present in cells of invasive squamous cell carcinoma in cases 2 and 3. HPV 6 and 11 were detected only in the condyloma area in case 2. HPV 30 was seen only in the condyloma area in case 3. This report emphasizes the need for biopsies of all unusually persistent or treatment-resistant condylomas, particularly in young and/or immunoisuppressed patients.

Musgos da Gruta de Mirassol, São Paulo

Na Gruta de Mirassol foram encontradas 27 espécies de musgos pertencentes a 23 gêneros de 19 famílias. Racopilum tomentosum (Hedw.) Brid., Helicophyllum torquatum (Hook.) Brid. e Hyophila involuta (Hook.) Jaeg. & Sauerb. são as espécies mais abundantes. Brachymenium acuminatum Harv., Cyclodictyon varians (Sull.) O. Kuntze, Entodontopsis leucostega (Brid.) Buck & Ireland, Fissidens mollis Mitt., F. weirii Mitt., Hyophila involuta (Hook.) Jaeg. & Sauerb. e Trichosteleum fluviale (Mitt.) Jaeg. estão sendo referidas pela primeira vez para o estado de São Paulo.

Expanding the Clinical and Genetic Spectrum of Human CD40L Deficiency: The Occurrence of Paracoccidioidomycosis and Other Unusual Infections in Brazilian Patients

CD40 ligand (CD40L) deficiency or X-linked hyper-IgM syndrome (X-HIGM) is a well-described primary immunodeficiency in which Pneumocystis jiroveci pneumonia is a common clinical feature. We have identified an unusual high incidence of fungal infections and other not yet described infections in a cohort of 11 X-HIGM patients from nine unrelated Brazilian families. Among these, we describe the first case of paracoccidioidomycosis (PCM) in X-HIGM. The molecular genetic analysis of CD40L was performed by gene sequencing and evaluation of CD40L protein expression. Nine of these 11 patients (82%) had fungal infections. These included fungal species common to CD40L deficiency (P. jiroveci and Candida albicans) as well as Paracoccidioides brasiliensis. One patient presented with PCM at age 11 years and is now doing well at 18 years of age. Additionally, one patient presented with a simultaneous infection with Klebsiella and Acinetobacter, and one with condyloma caused by human papilloma virus. Molecular analysis revealed four previously described CD40L mutations, two novel missense mutations (c.433 T>G and c.476 G>C) resulting in the absence of CD40L protein expression by activated CD4(+) cells and one novel insertion (c.484_485insAA) within the TNFH domain leading to a frame shift and premature stop codon. These observations demonstrated that the susceptibility to fungal infections in X-HIGM extends beyond those typically associated with X-HIGM (P. jiroveci and C. albicans) and that these patients need to be monitored for those pathogens.

(Table T1) Radiolaria abundance of ODP Hole 175-1082A

A primary objective of Leg 175 was to investigate the upwelling history of the Benguela Current. Upwelling along the coast is found over the shelf in several well-established cells, as well as along the shelf-slope break, and extends over the 1000-m isobath. Streaming filaments along the coast also carry upwelled water off shore (Shannon, 1985). The upwelled nutrient-rich waters are sourced from the South Atlantic central water mass, which is a mixture of subtropical and subantarctic water masses. Below the central water mass lies Antarctic intermediate water (Shannon and Hunter, 1988, doi:10.2989/025776188784480735; Stramma and Peterson, 1989, doi:10.1175/1520-0485(1989)019<1440:GTITBC>2.0.CO;2). The upwelling system supports a robust marine community (Shannon and Pillar, 1986) where radiolarians are abundant (Bishop et al., 1978, doi:10.1016/0146-6291(78)90010-3). The endemic nature of radiolarians makes them useful in reconstructing the paleocirculation patterns. The biogeographic distribution of many species is limited by water-mass distribution. In a given geographic region, species may also have discrete depth habitats. However, their depth of occurrence can change worldwide because the depths of water masses vary with latitude (Boltovskoy, 1999). Consequently, species found at shallow depths at high latitudes (cold-water fauna) are observed deeper in the water column at lower latitudes. The low-latitude submergence of cold-water species broadens their distribution, resulting in species distributions that can cover multiple geographic regions (Kling, 1976, doi:10.1016/0011-7471(76)90880-9; Casey, doi:10.1016/0031-0182(89)90017-5; 1971; Boltovskoy, 1987, doi:10.1016/0377-8398(87)90014-4). Since radiolarian distribution is closely related to water-mass distribution and controlled by climatic conditions rather than geographic regions, similar assemblages characterize the equatorial, subtropical, transition, subpolar, and polar regions of ocean basins (Petrushevskaya, 1971a; Casey, 1989, doi:10.1016/0031-0182(89)90017-5; Boltovskoy, 1999). Numerous radiolarian species found in water masses in the Angola and Benguela Current systems have also been observed in plankton net samples, sediment traps, and surface-sediment studies in the Atlantic sector of the Southern Ocean, where they exhibited particular water-mass affinities (Abelmann, 1992a, doi:10.1007/BF00243107; Abelmann 1992b, doi:10.1007/BF00243108; Abelmann and Gowing, 1997, doi:10.1016/S0377-8398(96)00021-7). This report presents data on the radiolarian fauna recovered from Site 1082 sediments in the form of a survey of species reflecting the latitudinal migration of the Angola-Benguela Front and upwelling. The data constitute a time series of relative radiolarian abundances at very high resolution (every 20 cm) of the upper 12 m of Hole 1082A.

Lithology, biostratigraphy, and geochemistry of the Black Sea sediments, DSDP Leg 42 (pt. 2) data

The monograph presents results of deep-sea drilling in the Black Sea carried out in 1975. Detailed lithological, biostratigraphic and geochemical studies of Miocene-Holocene sediments have been carried out by specialists from institutes of the USSR Academy of Sciences, Moscow State University and other organizations. Drilling results are compared with geophysical data. Geological history of the Black Sea basin is considered as well.