Generation of human neutralizing monoclonal antibodies against the 2009 pandemic H1N1 virus from peripheral blood memory B lymphocytes

The 2009 H1N1 influenza pandemic demonstrated the significance of a global health threat to human beings. Although pandemic H1N1 vaccines have been rapidly developed, passive serotherapy may offer superior immediate protection against infections in children, the elderly and immune-compromised patients during an influenza pandemic. Here, we applied a novel strategy based on Epstein–Barr virus (EBV)-immortalized peripheral blood memory B cells to screen high viral neutralizing monoclonal antibodies (MAbs) from individuals vaccinated with the 2009 pandemic H1N1 vaccine PANFLU.1. Through a massive screen of 13 090 immortalized memory B-cell clones from three selected vaccinees, seven MAbs were identified with both high viral neutralizing capacities and hemagglutination inhibition (HAI) activities against the 2009 pandemic H1N1 viruses. These MAbs may have important clinical implications for passive serotherapy treatments of infected patients with severe respiratory syndrome, especially children, the elderly and immunodeficient individuals. Our successful strategy for generating high-affinity MAbs from EBV-immortalized peripheral blood memory B cells may also be applicable to other infectious or autoimmune diseases.     

Improving oral healthcare using academic detailing – design of the ADVOCATE Field Studies

Background: Academic detailing (AD) is a defined form of educational outreach that can be deployed to intrinsically motivate practitioners towards improving quality of care. This paper describes the design of the ADVOCATE Field Studies. This proof of concept study aims to evaluate the feasibility, acceptability and usefulness of AD, reinforced with feedback information to promote prevention-oriented, patient-centred and evidence-based oral healthcare delivery by general dental practitioners (GDPs).

Methods: Six groups of GDPs will be recruited; two groups of six to eight GDPs in each of three countries – the Netherlands, Germany and Denmark. GDPs will meet for four Academic Detailing Group (ADG) meetings for open discussions using comparative feedback data to stimulate debate about their dental practice performance and care delivery. Group meetings will be moderated using the AD methodology. Qualitative data will be collected through focus group interviews, an online discussion forum, field notes and debriefs of ADG meetings and analysed by conventional content analysis using MaxQDA software.

Discussion: The results of the study will provide novel information on the feasibility, perceived acceptability and usefulness of AD and feedback data for GDPs to improve oral healthcare delivery.     

Prostate cancer risk in men with prostate and breast cancer family history: results from the REDUCE study (R1)

Abstract. Thomas J‐A II, Gerber L, Moreira DM, Hamilton RJ, Bañez LL, Castro‐Santamaria R, Andriole GL, Isaacs WB, Xu J, Freedland SJ (Durham VA Medical Center, Durham, NC, USA; Duke University School of Medicine, Durham, NC, USA; The Author Smith Institute for Urology, New Hyde Park, NY, USA; Memorial Sloan‐Kettering Cancer Center, New York, NY, USA; GlaxoSmithKline, Research Triangle Park, NC, USA; Washington University School of Medicine, St. Louis, MO, USA; Johns Hopkins Hospital, Baltimore, MD, USA; Wake Forest University, Winston‐Salem, NC, USA; and Duke University School of Medicine, Durham, NC, USA). Prostate cancer risk in men with prostate and breast cancer family history: results from the REDUCE study (R1). J Intern Med 2012; 272 : 85–92. Background. To what degree the associations between PCa risk and family history of prostate cancer (PCa) and/or breast cancer (BCa) are attributable to screening biases is unclear. We examined these questions within the REDUCE study, where biopsies were largely independent of prostate specific antigen (PSA) minimizing screening biases. Methods. Data were from REDUCE, which tested dutasteride 0.5 mg daily for PCa risk reduction in men with PSA 2.5–10.0 ng mL^?1 and a negative prestudy biopsy. Among men undergoing at least one on‐study biopsy with complete data (n = 6415; 78.1%), the association between family history and PCa risk was tested using multivariate logistic regression adjusting for clinicodemographic characteristics. Results. A family history of PCa alone was associated with increased PCa diagnosis (OR: 1.47, 95%CI: 1.22–1.77). In North America, PCa family history was not related to PCa diagnosis (OR: 1.02, 95%CI: 0.73–1.44), whereas outside North America, PCa family history was significantly related to diagnosis (OR: 1.72, 95%CI: 1.38–2.15) (P‐interaction = 0.01). A family history of both PCa and BCa (OR: 2.54, 95%CI: 1.72–3.75) but not BCa alone (OR: 1.04, 95%CI: 0.84–1.29) was associated with increased PCa risk versus no family history and irrespective of geographical region. Conclusions. In REDUCE, PCa family history was significantly related to PCa diagnosis, although only for men outside North America. The presence of both PCa and BCa family history significantly increased risk versus PCa family history alone, irrespective of geographical region. Ultimately, our observations may support the need for changes in how we address family history in terms of both risk of PCa diagnosis and general risk stratification.     

Intratumoral inflammation is associated with more aggressive prostate cancer

Purpose

Inflammation may play a role in the development and progression of many cancers, including prostate cancer. We sought to test whether histological inflammation within prostate cancer was associated with more aggressive disease.

Methods

The slides of prostatectomy specimens were reviewed by a board-certified pathologist on 287 men from a Veterans Affairs Medical Center treated with radical prostatectomy from 1992 to 2004. The area with the greatest tumor burden was scored in a blinded manner for the degree of inflammation: absent, mild, or marked. We used logistic and Cox proportional hazards regression analysis to examine whether categorically coded inflammation score was associated with adverse pathology and biochemical progression, respectively.

Results

No inflammation was found in 49 men (17 %), while 153 (53 %) and 85 (30 %) had mild and marked inflammation. During a median follow-up of 77 months, biochemical recurrence occurred among 126 (44 %) men. On multivariate analysis, more inflammation was associated with greater risk of positive margins, capsular penetration, and seminal vesicle invasion (all p < 0.05). Marked inflammation was associated with increased PSA recurrence risk when adjusting for preoperative features only (HR 2.08, 95 % CI 1.02–4.24), but not after adjusting for pathologic features.

Conclusions

Inflammation within prostate cancer was associated with more advanced disease, although it is unclear whether aggressive disease caused increased inflammation or inflammation caused aggressive disease.     

Urolithiasis in infants: evaluation of risk factors

Objective

Urolithiasis in infants is not a very rare situation in Turkey, and the incidence has been increasing in recent years. The purpose of this paper was to investigate the clinical characteristics, metabolic and anatomic risk factors for urolithiasis and microlithiasis in infants.

Methods

The cases of 178 infants (63 girls, 115 boys), who were referred to our department between 1999 and 2009 with urolithiasis, were evaluated.

Results

The mean age at diagnosis of stone disease was 11.5 months (range, 10 days–24 months). The mean follow-up duration was 33.6 months (1.2–110 months). The major clinical symptoms of our patients were restlessness in 24 children (13.5%) and vomiting in 23 (13%). Thirty-five infants (19.7%) had a urinary tract abnormality; vesico-ureteral reflux was the most common abnormality (12.9%). Hypercalciuria and hyperuricosuria were detected in 46 and 56%, respectively. Stone analysis was performed in 56 infants, and calcium oxalate was determined in 36 patients (64.3%). A family history of urolithiasis, presenting symptoms and underlying metabolic abnormalities were similar for patients with microlithiasis and those with larger stones. However, infants with microlithiasis had higher ratios for history of vitamin D administration and feeding with formula. Surgical treatment was performed in 42 infants and extracorporeal shock wave lithotripsy in 30 infants.

Conclusion

Our results showed that urolithiasis in infants may present nonspecific symptoms and may even be asymptomatic and that a positive family history for urolithiasis, urologic abnormalities, metabolic disorders, urinary tract infections, vitamin D administration and feeding with formula may increase the occurrence of urolithiasis in infants.     

The effect of collagen,Interleukin-l α and glicosaminoglycan on the neovascularization of central nervous system

Abstract

Neovascularization, the development of a new microvasculature, has an important role in physiological and pathological processes. The vascular changes in the brain can be easily detected because the proliferation of endothelial cells in its vascular structure is quite small, and so constitutes a good model for neovascularization studies. In the present investigation, to induce intracerebral neovascularization, we implanted collagen, Interleukin-l alpha (IL-lα) and glicosaminoglycan into the brain ofpigs, in order to test the hypothesis that IL-l α, collagen and glicosaminoglycan play a pivotal. role in the process of neovascularization. Both pure collagen and collagen combined with IL-l a induced neovascularization according to light-electron microscopic findings and values of enzymes' activities. In particular, collagen combined with IL-lα synergically affected the increase of neovascularization. However, glicosarrinoglycan did not affect it significantly. Although the results of this study provided us with some interesting data indicating the beneficial effects of collagen combined with IL-1α on neovascularization, further studies should be done to study the short term effect of these biochemical substances. [Neural Res 1998; 20: 513-525]