Objective To quantify the prevalence of incidental findings on magnetic resonance imaging (MRI) of the brain.Design Systematic review and meta-analysis of observational studies.Data sources Ovid Medline (1950 to May 2008), Embase (1980 to May 2008), and bibliographies of relevant articles.Review methods Two reviewers sought and assessed studies of people without neurological symptoms who underwent MRI of the brain with or without intravenous contrast for research purposes or for occupational, clinical, or commercial screening.Main outcome measures Overall disease specific and age specific prevalence of incidental brain findings, calculated by meta-analysis of pooled proportions using DerSimonian-Laird weights in a random effects model.Results In 16 studies, 135 of 19 559 people had neoplastic incidental brain findings (prevalence 0.70%, 95% confidence interval 0.47% to 0.98%), and prevalence increased with age (χ2 for linear trend, P=0.003). In 15 studies, 375 of 15 559 people had non-neoplastic incidental brain findings (prevalence 2.0%, 1.1% to 3.1%, excluding white matter hyperintensities, silent infarcts, and microbleeds). The number of asymptomatic people needed to scan to detect any incidental brain finding was 37. The prevalence of incidental brain findings was higher in studies using high resolution MRI sequences than in those using standard resolution sequences (4.3% v 1.7%, P<0.001). The prevalence of neoplastic incidental brain findings increased with age.Conclusions Incidental findings on brain MRI are common, prevalence increases with age, and detection is more likely using high resolution MRI sequences than standard resolution sequences. These findings deserve to be mentioned when obtaining informed consent for brain MRI in research and clinical practice but are not sufficient to justify screening healthy asymptomatic people.

We generated a monoclonal antibody, RG-1, that binds to highly conserved L2 residues 17 to 36 and neutralizes human papillomavirus 16 (HPV16) and HPV18. Passive immunotherapy with RG-1 was protective in mice. Antiserum to the HPV16 L2 peptide comprising residues 17 to 36 (peptide 17-36) neutralized pseudoviruses HPV5, HPV6, HPV16, HPV 18, HPV31, HPV 45, HPV 52, HPV 58, bovine papillomavirus 1, and HPV11 native virions. Depletion of HPV16 L2 peptide 17-36-reactive antibodies from cross-neutralizing rabbit and human L2-specific sera abolished cross-neutralization and drastically reduced neutralization of the cognate type. This cross-neutralization of diverse HPVs associated with cervical cancer, genital warts, and epidermodysplasia verruciformis suggests the possibility of a broadly protective, peptide-based vaccine.Minor capsid antigen L2 is a possible alternative to highly multivalent L1 virus-like-particle (VLP) vaccines to obtain broad protection against oncogenic human papillomaviruses (HPVs) (16). Vaccination with L2 as a full-length protein or as polypeptides protects animals against homologous-type viral challenges at both cutaneous and mucosal sites (2-4, 6, 12). Protection is not mediated by cellular immunity, suggesting the importance of neutralizing antibodies (5, 7). L2 is subdominant in the context of L1/L2 VLPs (19), but antibodies elicited by recombinant L2 immunogens are able to neutralize a remarkably broad range of HPV genotypes (15). This suggests that neutralizing epitopes of L2 may be conserved across HPV types due to some critical viral function (13). Furthermore, it raises the possibility that a single L2 protein-or peptide-based vaccine might provide comprehensive protection against the HPV types causing genital cancer and genital warts and possibly even those associated with cutaneous warts and epidermodysplasia verruciformis (EV).Identification of neutralizing epitopes within HPV16 L2. The rational design of a broadly protective L2-based preventive vaccine requires knowledge of the relevant neutralizing epitopes. To identify the neutralizing epitopes in L2, we vaccinated BALB/c mice with full-length six-His-tagged HPV16 L2 protein and produced hybridomas by using standard procedures (18). Of the 100 supernatants reactive with L2 protein, only 45 reacted with HPV16 L1/L2 pseudovirions, and only one (RG-1) neutralized HPV16 pseudovirus and was cloned. The RG-1 supernatant exhibited a neutralizing titer of 1,280 and also reacted with HPV16 L1/L2 pseudivirions by an enzyme-linked immunosorbent assay (ELISA). RG-1 and another four monoclonal antibodies (MAbs) that showed the highest ELISA reactivities with HPV16 pseudovirions were all the immunoglobulin G1() [IgG1()] isotype and reacted with HPV16 L2 protein by Western blotting (Table 1).Each MAb was screened for reactivity with 56 20-mer peptides of HPV16 L2 that overlapped each other by 12 amino acids ( Table 1). The neutralizing MAb RG-1 reacted with a peptide comprising residues 17 to 36 of HPV 16 L2 (peptide 17-36) (Fig. 1A) but not the ...

Persistent infection with the high-risk subset of genitotropic human papillomavirus (HPV) genotypes is a necessary cause of cervical cancer. Given the global burden of cervical cancer, a low-cost, broadly protective vaccine is needed. RG-1 is a crossneutralizing and protective monoclonal antibody that recognizes residues 17-36 of HPV16 minor capsid protein L2. Because this epitope is highly conserved in divergent HPV types, we determined whether vaccination with HPV16 L2 17-36 peptide is broadly protective. The peptide was administered to BALB/c mice three times at monthly intervals, either alone or in the context of a synthetic lipopeptide vaccine candidate (P25-P2C-HPV) produced by linkage of the HPV peptide with a broadly recognized T helper epitope (P25) and the Toll-like receptor-2 (TLR2) ligand dipalmitoyl-S-glyceryl cysteine (P2C). In contrast to vaccination with the L2 17-36 peptide or P25-P2C alone, a potent L2-specific antibody response was generated to the P25-P2C-HPV lipopeptide when delivered either s.c. or intranasally. Sera from mice vaccinated with the P25-P2C-HPV lipopeptide neutralized not only HPV16 pseudovirions but also other evolutionarily divergent oncogenic genital (HPV18, HPV45) and cutaneous (HPV5, BPV1) types. The L2-specific antibody response depended on MHC class II, CD40, and MyD88 signaling. Additionally, vaccination with the P25-P2C-HPV lipopeptide protected mice from homologous challenge with HPV16 pseudovirions at cutaneous and genital sites and heterologous challenge with HPV45 pseudovirions. If provided in the appropriate context, therefore, HPV16 L2 17-36 might be used in a totally synthetic cross-protective HPV vaccine. G enitotropic human papillomavirus (HPV) infections are considered the most common sexually transmitted infection in the United States (1). The major manifestations of anogenital HPV include genital warts (condyloma acuminatum) and anogenital intraepithelial neoplasia. If left untreated, a small fraction of persistent high-risk HPV infections progresses to cancer. The presence of HPV DNA has been reported in 99.7% of cervical carcinomas worldwide, indicating that HPV infection is a necessary cause of this cancer and that this disease can be prevented by prophylactic HPV vaccination (2).Approximately 35 of the Ͼ100 subtypes of HPV are specific for the anogenital epithelium and have varying potentials for malignant transformation (3). Of the 15 oncogenic genital HPV types, HPV16 is the most common, followed by HPV18 and HPV45 (contributing Ϸ50%, 20%, and 10%, respectively, of cervical cancer cases worldwide). Public health efforts have successfully reduced the incidence and mortality of cervical cancer with the implementation of cervical cytology screening programs. Women who do not undergo regular screening account for most of the patients with invasive cancers (4), and cervical cancer remains the second most common cause of cancer death in women worldwide and the most prevalent cancer in women of sub-Saharan Africa, Central America, south-central Asia, and Me...

Introduction Erectile function recovery (EFR) rates after radical prostatectomy (RP) vary greatly based on a number of factors, such as erectile dysfunction (ED) definition, data acquisition means, time-point postsurgery, and population studied. Aim To conduct a meta-analysis of carefully selected reports from the available literature to define the EFR rate post-RP. Main Outcome Measures EFR rate after RP. Methods An EMBASE and MEDLINE search was conducted for the time range 1985–2007. Articles were assessed blindly by strict inclusion criteria: report of EFR data post-RP, study population ≥50 patients, ≥1 year follow-up, nerve-sparing status declared, no presurgery ED, and no other prostate cancer therapy. Meta-analysis was conducted to determine the EFR rate and relative risks (RR) for dichotomous subgroups. Results A total of 212 relevant studies were identified; only 22 (10%) met the inclusion criteria and were analyzed (9,965 RPs, EFR data: 4,983 subjects). Mean study population size: 226.5, standard deviation = 384.1 (range: 17–1,834). Overall EFR rate was 58%. Single center series publications (k = 19) reported a higher EFR rate compared with multicenter series publications (k = 3): 60% vs. 33%, RR = 1.82, P = 0.001. Studies reporting ≥18-month follow-up (k = 10) reported higher EFR rate vs. studies with <18-month follow-up (k = 12), 60% vs. 56%, RR = 1.07, P = 0.02. Open RP (k = 16) and laparoscopic RP (k = 4) had similar EFR (57% vs. 58%), while robot-assisted RP resulted in a higher EFR rate (k = 2), 73% compared with these other approaches, P = 0.001. Patients <60 years old had a higher EFR rate vs. patients ≥60 years, 77% vs. 61%, RR = 1.26, P = 0.001. Conclusions These data indicate that most of the published literature does not meet strict criteria for reporting post-RP EFR. Single and multiple surgeon series have comparable EFR rates, but single center studies have a higher EFR. Younger men have higher EFR and no significant difference in EFR between ORP and LRP is evident.

Parotid gland masses are not particularly conducive to diagnostic accuracy and precision by fine needle aspiration. Accordingly, indiscriminant reliance on the fine needle aspiration findings at the expense of the clinical, radiographic, and intraoperative findings is unwarranted. Whether one uses the fine needle aspiration routinely or selectively in patients with parotid masses, the fine needle aspiration findings should contribute to, not displace, the overall diagnostic impression.

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Introduction Radical prostatectomy (RP) is a common technique for managing prostate cancer. Concern regarding functional outcomes in patients prompted the development of nerve sparing to improve recovery of erectile function. Aim To assess if a cumulative nerve damage grading system is a more precise predictor of recovery of erectile function as compared to the current “all-or-none” grading system. Methods Baseline demographic, medical history, and International Index of Erectile Function (IIEF)-erectile function domain (EFD) scores were collected. At the time of RP, patients were assigned a nerve sparing score (NSS) by their surgeon for each neurovascular bundle (left and right) to assess the quality of intraoperative nerve sparing (1—complete preservation, 4—complete resection). Patients completed IIEF questionnaires at 24 months after RP. Main Outcome Measures Group comparisons and multiple regression analyses were used to test the association between the NSS and IIEF-EFD scores for patients with preoperative EFD scores ≥24. Results A total of 173 patients were included in this analysis. Mean age for patients was 59, and 62% of patients had at least one comorbidity. Baseline EFD scores were comparable between all NSS assignments. At 24 months, EFD scores were reduced by 7.2, 11.6, 13.9, and 15.4 points for patients with NSS grades of 2, 3, 4, and 5–8, respectively (P &lt; 0.01). Multivariate analysis demonstrated lower NSS predicted recovery of erectile function at 24 months (P = 0.001), as did age (P = 0.001) and baseline EFD score (P = 0.02). Conclusions Our data support the adoption of a subjectively assigned NSS to more precisely predict erectile function outcomes and suggest that even minor nerve trauma significantly impairs the recovery of erectile function after procedures classically regarded as having achieved bilateral nerve sparing. Further studies are needed to identify the optimal NSS system.

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