Protection against heterologous human papillomavirus challenge by a synthetic lipopeptide vaccine containing a broadly cross-neutralizing epitope of L2.

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 cross-neutralizing 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.

Preoperative clinical and diagnostic characteristics of patients who require delayed IPP after primary Peyronies repair.

INTRODUCTION: Penile vascular abnormalities occur in a high proportion of patients with Peyronie's disease (PD). Penile duplex ultrasonography (PDU) and dynamic infusion cavernosometry and cavernosography (DICC) are tools that can be used to help tailor individualized treatment for patients undergoing surgical intervention for their PD. However, precisely which parameters can be used to predict those patients with PD at risk for developing erectile dysfunction (ED) after intervention without inflatable penile prosthesis (IPP) has not been previously elucidated. AIM: To evaluate preoperative vascular parameters that predispose PD patients for developing ED after intervention without IPP. METHODS: Twenty-six patients receiving surgical intervention for their PD at a single center were retrospectively identified. Of these, 11 (42.3%) opted for primary repair without placement of an IPP. Three (27.2%) of these 11 patients went on to develop ED postoperatively. MAIN OUTCOME MEASURES: We compared various demographic, PDU, and DICC parameters between patients who did and did not fail primary repair of their PD. RESULTS: Mean age and follow-up of patients who went on to develop ED after repair of PD without IPP were not significantly different (P < 0.05). Resistive index (RI) and end diastolic volume were significantly different between these two groups (P < 0.05), while peak systolic volume, flow to maintain, and pressure decay were not significantly different. An RI cutoff of <0.80 was found to identify all patients who would later develop ED and fail primary repair without IPP. CONCLUSIONS: Penile vascular assessment can aid in counseling patients about their risk of developing delayed ED after primary repair of PD. In our cohort of patients, PDU provided preoperative risk stratification for postoperative erectile dysfunction in men undergoing Peyronie's repair without IPP. We propose the prospective study of an RI cutoff to identify patients at risk of failing primary PD repair without IPP.

Erectile function recovery rate after radical prostatectomy: a meta-analysis.

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 >or=50 patients, >or=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 >or=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 >or=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.

Presentation and management of a patient with subcutaneous metastatic transitional cell carcinoma of the bladder.

BACKGROUND: A 60-year-old female with a 6-month history of muscle-invasive transitional cell carcinoma of the bladder presented with an enlarging subcutaneous lesion involving her right flank. She had previously undergone radical cystectomy, bilateral pelvic lymphadenectomy and ileal orthotopic neobladder reconstruction. INVESTIGATIONS: Axial fused fluorodeoxyglucose PET-CT of the chest, abdomen and pelvis, fine needle aspiration with direct ultrasound guidance, excisional biopsy and immunohistochemistry. DIAGNOSIS: Subcutaneous and liver metastases of transitional cell carcinoma. MANAGEMENT: Wide local excision of the subcutaneous lesion followed by combination gemcitabine-cisplatin chemotherapy. Gemcitabine was administered at a dose of 1,000 mg/m(2) on days 1, 8, and 15, and cisplatin was administered at a dose of 75 mg/m(2) on day 1; the schedule was repeated every 28 days for three cycles.

Findings on brain MRI from research studies of occupational exposure to known neurotoxicants.

OBJECTIVE: The expanding use of MRI in large-scale epidemiologic studies of CNS outcomes has led to increasing concern for the consistent handling of incidental findings. Our purpose is to identify the prevalence of incidental neuroradiologic abnormalities in an adult population with past occupational exposure to lead who underwent brain MRI as part of a large, longitudinal cohort study. MATERIALS AND METHODS: Structural MR images obtained for the research study were reviewed by a neuroradiologist on an ongoing basis for findings of clinical concern. The subjects were recruited as part of a longitudinal research study designed to examine the effects of past lead exposure on CNS structures. The cohort examined consisted of 589 men who previously worked at an organolead manufacturing facility and had a wide range of lead exposure durations and intensities. MR images were also reviewed from 67 population-based control subjects from the same study who had no history of occupational lead exposure. RESULTS: Incidental findings were detected in 84% (548/656) of research subjects. Of the 548 subjects with abnormalities, 30% (167) required no referral, 51% (280) required routine referral, 17% (93) required urgent referral, and 1.5% (8) required immediate referral. Incidental findings of all categories were observed in a larger percentage of older subjects, aged 60 years and above. Using multivariable logistic regression analysis, we found that age (p < 0.0001), but not lead history, was associated with an increased risk of incidental neuroradiologic abnormalities. CONCLUSION: In the population examined, there was a high prevalence of incidental brain and head and neck abnormality. Of particular concern were the serious health problems observed requiring urgent or immediate referral in 18.5% of the subjects. These findings underscore the need for radiologists to evaluate the anatomic images generated by research studies, particularly those with an older population base.

Surgical reconstruction of the male urethral diverticulum.

OBJECTIVES: To describe the outcomes and reconstructive techniques used for men with symptomatic urethral diverticula in an attempt to standardize treatment based on the length of the urethral defect after diverticulum excision and the type of repair used. Urethral diverticula are rare in men and may be either congenital or acquired. METHODS: Between 2003 and 2008, 13 men were treated surgically for symptomatic urethral diverticula at a single institution by a single surgeon (C.M.G.). A total of 6 (46.2%) patients had urethral defects of < 4 cm and underwent excision of the diverticulum with primary anastomosis. Substitution urethroplasty using either penile skin or buccal mucosa was used in 7 (53.8%) patients with urethral defects of >or= 4 cm. Demographic and preoperative characteristics were compared among patients according to the length of the urethral defect. RESULTS: The mean age of men at the time of surgery was 38.4 years (+/- 13.0; range, 20.4-63.7), with a median follow-up time of 21.7 (+/- 29.0; range, 0.9-84.0) months. Neither age at the time of surgery, length of follow-up, or diverticulum volume was significantly different between men who underwent primary repair vs substitution urethroplasty. The overall success rate was 92% (12/13) with an overall complication rate of 42% at intermediate follow-up. CONCLUSIONS: Outcomes after excision and primary anastomosis for diverticula associated with defects of < 4 cm were similar to outcomes after diverticulum excision and substitution urethroplasty for defect of >or= 4 cm.

A recurrent network in the lateral amygdala: a mechanism for coincidence detection.

Synaptic changes at sensory inputs to the dorsal nucleus of the lateral amygdala (LAd) play a key role in the acquisition and storage of associative fear memory. However, neither the temporal nor spatial architecture of the LAd network response to sensory signals is understood. We developed a method for the elucidation of network behavior. Using this approach, temporally patterned polysynaptic recurrent network responses were found in LAd (intra-LA), both in vitro and in vivo, in response to activation of thalamic sensory afferents. Potentiation of thalamic afferents resulted in a depression of intra-LA synaptic activity, indicating a homeostatic response to changes in synaptic strength within the LAd network. Additionally, the latencies of thalamic afferent triggered recurrent network activity within the LAd overlap with known later occurring cortical afferent latencies. Thus, this recurrent network may facilitate temporal coincidence of sensory afferents within LAd during associative learning.

Predictors of surgical outcome and survival among elderly women diagnosed with ovarian and primary peritoneal cancer.

OBJECTIVE: To identify perioperative variables that will predict surgical outcome and survival among elderly women diagnosed with ovarian and primary peritoneal cancer. METHODS: A retrospective review of 78 women>or=75 years treated for ovarian and primary peritoneal cancer from 1/1/90 to 06/30/04 was performed. Patients were categorized in two groups based on optimal versus suboptimal cytoreductive surgery. Perioperative variables were compared across the two groups by univariate and multivariate logistic regression analysis to evaluate the impact on survival. RESULTS: The median age at the time of diagnosis was 79.3 years. Overall, 50% of the patients underwent optimal cytoreductive surgery. Patients with low perioperative serum albumin levels were associated with a 2.4-fold increased risk of suboptimal cytoreductive surgery (95% CI 1.02-5.88, p=0.04). Median survival of patients that underwent cytoreductive surgery was 19 months. As expected, survival analysis showed that patients with suboptimal cytoreductive surgery had a lower survival (median=17 months) than patients with optimal surgery (median=62 months, p=0.00). Patients>or=80 years were associated with a nearly 2-fold increase in the risk of mortality (95% CI 1.05-3.54, p=0.03), while albumin levels of >or=3.7 g/dl were associated with a 40% reduction in risk of mortality (95% CI 0.41-0.89, p=0.01). CONCLUSIONS: Optimal cytoreductive surgery is feasible in many elderly patients. Women>or=80 years and with poor nutritional status are associated with a poor survival outcome. Perioperative variables such as these can be used to identify the elderly patients that are most likely to be suboptimally cytoreduced and thus have a dismal survival outcome.