Incidence of cervical dyskaryosis in Ireland: report of a five-year audit

The implementation of a national cervical screening programme in Ireland will require agreement on achievable standards in reporting cervical cytology similar to those published by the NHS cervical screening programme. Due to the opportunistic nature of screening in the Republic of Ireland, national incidence figures for uterine cervical disease are not available. An audit of our practice was performed to find the incidence of human papilloma virus related cervical disease in our population. Our laboratory reported 158,066 cases from 1996-2000. The overall rate of dyskaryosis increased from 3.6% to 7.9%, mostly due to increased low grade dyskaryosis (up from 2.3% to 6.0%). High grade dyskaryosis also increased (from 1.3% to 1.9%), particularly in the under-25 year age group who account for a growing proportion of high grade dyskaryosis (from 15.4% of all high grade diagnoses in 1996 to 23.0% in 2000). The positive predictive value of a diagnosis of high grade dyskaryosis remained stable between 76.0 and 79.5%. While opportunistic screening data may not be directly applicable to the entire screening population it is hoped that these data may form a foundation on which to estimate national incidence figures and define achievable standards for cervical screening cytology in Ireland.     

Expression and self-assembly of recombinant capsid protein from the antigenically distinct Hawaii human calicivirus.

The Norwalk and Hawaii viruses are antigenically distinct members of the family Caliciviridae and are considered to be important etiologic agents of epidemic gastroenteritis, with most studies focusing on the role of Norwalk virus. To further investigate the importance of Hawaii virus, Hawaii virus-like particles (VLPs) were produced by expression of its capsid protein in the baculovirus system and these VLPs were used as the antigen in an enzyme-linked immunosorbent assay that was efficient in the detection of a serologic response to Hawaii virus. The ready availability of Hawaii VLPs should enable larger-scale epidemiological studies to further elucidate the importance of this agent.     

Use of live cold-adapted influenza A H1N1 and H3N2 virus vaccines in seropositive adults.

To investigate the immunogenicity and protective efficacy of cold-adapted influenza vaccine in individuals with underlying immunity to influenza A virus, we administered cold-adapted H1N1 and H3N2 vaccines to adults with prevaccination serum hemagglutination inhibition antibody titers of 1:16 or more and challenged them 1 month afterwards with homologous wild-type influenza A virus. Both cold-adapted vaccines were immunogenic in seropositive adults. In addition, individuals receiving cold-adapted vaccines had lower rates of virus shedding and illness following challenge with wild-type influenza virus than did unvaccinated seropositive volunteers.     

Development of an enzyme immunoassay for the Hawaii agent of viral gastroenteritis

The Hawaii agent is a Norwalk-like virus of acute gastroenteritis in humans which is antigenically distinct from the prototype Norwalk agent. We established a solid phase sandwich type microtiter enzyme immunoassay (EIA) for Hawaii antigen employing sera and stools from experimentally challenged volunteers as reagents. This assay detected the Hawaii agent in stools from 3 of 8 volunteers who were ill after oral challenge with the Hawaii agent, including one specimen which was positive to a dilution of 1/320. Virus shedding occurred on days 3 to 7 after challenge. The Hawaii-positive stools did not react in the EIAs for Norwalk and Snow Mountain agent (SMA), nor did Norwalk or SMA-positive stools react in the Hawaii EIA. Human rotavirus, enteric adenovirus, feline calicivirus, and several enteroviruses also did not react in the Hawaii EIA. A blocking EIA to detect serum antibody to the Hawaii agent was also developed employing a diarrheal stool containing Hawaii as a source of antigen. Serum antibody rises were detected in 15 of 16 individuals with experimentally induced illness after challenge and in 3 of 5 individuals who remained well after challenge. The EIA for the Hawaii agent should permit epidemiologic studies of the Hawaii agent to be carried out as well as allow further characterization of the Hawaii virion.     

Viral infections of the respiratory tract: prevention and treatment

The rapid discovery of specific viral agents as the cause of many acute respiratory diseases was accompanied by considerable optimism that vaccines or other control measures could be developed quickly. Subsequent experience has demonstrated that effective control of these important public health problems has been an elusive goal. However, recent exciting developments in our understanding of the molecular biology and immunology of these virusesay provide the basis for more effective strategies in the future.     

Decreased incidence of arterial thrombosis using heparin-bonded intraaortic balloons

BACKGROUND: This experimental study sought to determine whether heparin-bonding of intraaortic balloons (IAB) would decrease the incidence of arterial thrombosis in the absence of systemic heparinization. METHODS: In 25 adult pigs, a 9F, 40-mL IAB was inserted into the femoral artery and positioned just below the takeoff of the left subclavian artery for 9 hours. Five animals received systemic heparin, 10 animals had no heparin, and another 10 animals received no heparin but the IAB was heparin-bonded (Duraflo II). Thrombus formation was assessed using a numerical scoring system (0 = no thrombosis to 3 = thrombus >5 cm or evidence of luminal compromise). RESULTS: Animals receiving heparin and heparin-bonded IAB had no thrombus formation around the IAB (mean +/- SE; 0 +/- 0.00 heparin versus 1.55 +/- 0.29 no heparin versus 0 +/- 0.00 heparin-bonded; p < 0.005), at the insertion site (0 +/- 0.00 heparin versus 1.55 +/- 0.29 no heparin versus 0 +/- 0.0 heparin-bonded; p < 0.005), and in the distal femoral artery (0 +/- 0.00 heparin versus 2.00 +/- 0.23 no heparin versus 0 +/- 0.00 heparin-bonded; p < 0.005). CONCLUSIONS: Heparin-bonding of the IAB significantly decreases thrombus formation in the absence of systemic heparinization.     

A fiberoptic bronchoscopy assistant program

The increased popularity of bronchoscopy performed outside the operating room has created a need for the bronchoscopy assistant service. The Stanford (Calif) University service is described here as a guide for departments establishing a bronchoscopy assistant service or restructuring an existing one.     

Guidelines and considerations for conducting experiments using tissue microarrays

Tissue microarrays (TMAs) represent a powerful method for undertaking large‐scale tissue‐based biomarker studies. While TMAs offer several advantages, there are a number of issues specific to their use which need to be considered when employing this method. Given the investment in TMA‐based research, guidance on design and execution of experiments will be of benefit and should help researchers new to TMA‐based studies to avoid known pitfalls. Furthermore, a consensus on quality standards for TMA‐based experiments should improve the robustness and reproducibility of studies, thereby increasing the likelihood of identifying clinically useful biomarkers. In order to address these issues, the National Cancer Research Institute Biomarker and Imaging Clinical Studies Group organized a 1‐day TMA workshop held in Nottingham in May 2012. The document herein summarizes the conclusions from the workshop. It includes guidance and considerations on all aspects of TMA‐based research, including the pre‐analytical stages of experimental design, the analytical stages of data acquisition, and the postanalytical stages of data analysis. A checklist is presented which can be used both for planning a TMA experiment and interpreting the results of such an experiment. For studies of cancer biomarkers, this checklist could be used as a supplement to the REMARK guidelines.     

Effect of Display Resolution on Time to Diagnosis with Virtual Pathology Slides in a Systematic Search Task

Performing diagnoses using virtual slides can take pathologists significantly longer than with glass slides, presenting a significant barrier to the use of virtual slides in routine practice. Given the benefits in pathology workflow efficiency and safety that virtual slides promise, it is important to understand reasons for this difference and identify opportunities for improvement. The effect of display resolution on time to diagnosis with virtual slides has not previously been explored. The aim of this study was to assess the effect of display resolution on time to diagnosis with virtual slides. Nine pathologists participated in a counterbalanced crossover study, viewing axillary lymph node slides on a microscope, a 23-in 2.3-megapixel single-screen display and a three-screen 11-megapixel display consisting of three 27-in displays. Time to diagnosis and time to first target were faster on the microscope than on the single and three-screen displays. There was no significant difference between the microscope and the three-screen display in time to first target, while the time taken on the single-screen display was significantly higher than that on the microscope. The results suggest that a digital pathology workstation with an increased number of pixels may make it easier to identify where cancer is located in the initial slide overview, enabling quick location of diagnostically relevant regions of interest. However, when a comprehensive, detailed search of a slide has to be made, increased resolution may not offer any additional benefit.