The rotavirus vaccine

A rotavirus vaccine was recently licensed by the Food and Drug Administration and is likely to be recommended for use in all infants by both the Advisory Committee on Immunization Practices and the American Academy of Pediatrics. If used as recommended, the vaccine is likely to prevent much of the 500,000 physician visits, 50,000 hospitalizations, and 20 to 40 deaths caused by rotavirus infections every year in the United States. An understanding of the biology, immunology, and pathogenesis of rotavirus infection will help to explain the strengths and limitations of the rotavirus vaccine.     

School based screening for hypothyroidism in Down's syndrome by dried blood spot TSH measurement.

OBJECTIVE: To determine the feasibility of annual hypothyroid screening of children with Down's syndrome by measuring thyroid stimulating hormone (TSH) on dried blood spots at school, and to describe the outcome in positive children. DESIGN: Establishment of a register of school children with Down's syndrome, and procedures for obtaining permission from parents, annual capillary blood samples, TSH measurement, and clinical assessment of children with TSH values > 10 mU/litre. SUBJECTS: All school age children with Down's syndrome within Lanarkshire and Glasgow Health Boards during 1996-7 and 1997-8. RESULTS: 200 of 214 school children with Down's syndrome were screened. Four of the unscreened children were receiving thyroxine treatment, and only 5 remained unscreened by default. 15 of the 200 children had capillary TSH > 10 mU/litre, and all but 1 had evidence of Hashimoto's thyroiditis. Seven of the 15 children started thyroxine treatment immediately, 6 with a pronounced rise in venous TSH and subnormal free thyroxine (fT4), and one with mildly raised TSH and normal fT4 but symptoms suggesting hypothyroidism. Eight children with mildly raised venous TSH and normal fT4 were left untreated; 1 year after testing positive, fT4 remained > 9 pmol/litre in all cases, but 4 children were started on thyroxine because of a rise in TSH. TSH fell in 3 of the 4 remaining children and there was a marginal rise in 1; all remain untreated. The prevalence of thyroid disease in this population is >/= 8.9%. CONCLUSION: Dried blood spot TSH measurement is effective for detecting hypothyroidism in Down's syndrome and capillary sampling is easily performed at school. The existing programme could be extended to the whole of Scotland within a few years.     

Executive control and dimensions of problem behaviors in preschool children

Background: Despite the widespread recognition of the importance of executive control (EC) in externalizing psychopathology, the relation between EC and problem behavior has not been well characterized, particularly in typically developing preschoolers. Method: Using the sample, battery of laboratory tasks, and latent variable modeling methods described in Wiebe, Espy, and Charak (2008) , systematic latent dimensions of parent‐rated problem behavior, measured by integrating scales from developmental and clinical traditions, were determined empirically, and then were related to EC. Results: Substantial relations between EC and problem behaviors were revealed by extracting the common variance of interest and eliminating extraneous variance, which were robust to estimated child intelligence and differed somewhat in preschool boys and girls. Conclusion: Preschool EC measured by laboratory tasks appears to tap abilities that strongly and robustly support broad control processes enabling behavioral regulation across cognitive and emotional domains.     

Boosting with poxviruses enhances Mycobacterium bovis BCG efficacy against tuberculosis in guinea pigs

Tuberculosis is rising in the developing world due to poor health care, human immunodeficiency virus type 1 infection, and the low protective efficacy of the Mycobacterium bovis BCG vaccine. A new vaccination strategy that could protect adults in the developing world from tuberculosis could have a huge impact on public health. We show that BCG boosted by poxviruses expressing antigen 85A induced unprecedented 100% protection of guinea pigs from high-dose aerosol challenge with Mycobacterium tuberculosis, suggesting a strategy for enhancing and prolonging the efficacy of BCG.     

Omalizumab in asthma

Omalizumab is a humanized mouse monoclonal antibody that binds specifically to the constant region of the immunoglobulin (Ig)E heavy chain. Omalizumab exerts its effects by reducing free serum IgE levels and FcepsilonRI expression on several cell types. These effects have been shown to result in decreased airway inflammation and clinical improvement. In multiple studies, omalizumab has been shown to be efficacious in the treatment of moderate-to-severe persistent asthma and is currently approved by the US Food and Drug Administration for the treatment of moderate-to-severe allergic asthma in patients age 12 yr and older. Moreover, omalizumab has been demonstrated to be effective in the treatment of children and adults with seasonal and perennial allergic rhinitis. Postmarketing surveillance has shown omalizumab to be a relatively safe and well-tolerated medication.     

Epoxy-resin injection of the cerebral arterial microvasculature: An evaluation of the limits of spatial resolution in 8 Tesla MRI

The purpose of this study was to quantify the spatial resolution of microscopic arteries on magnetic resonance images acquired at 8 Tesla (T). Techniques similar to those used for standard MRI of the human brain in vivo at 8 T were utilized to generate high-resolution gradient echo (GE) images of a whole postmortem human brain whose common carotid arterial system had been injected with an epoxy-resin. Single slice images, along with summed images of up to 5 contiguous slices, were then compared to color digital photographs detailing the distribution of the arterial system on the surface of the same injected brain. There was excellent MR visualization of the microscopic cerebral arteries down to a spatial resolution of 200 microm. Through the use of an 8 T whole-body MRI scanner and standard GE imaging sequences, microscopic arterial structures can be clearly resolved down to a dimension of 200 microm.     

Standardization for image characteristics in telemammography using genetic and nonlinear algorithms

As the soft copy reading and computer assisted diagnosis (CAD) in mammography become more and more important, the standardization of digital images becomes paramount. Telemammography and telemedicine requires the standardization for image characteristics, such as image resolution, bit-depth and intensity response. Soft copy reading and CAD in mammography are both dependent on the characteristics of the source of the digital data, either direct digital mammography or digitized screen-film mammography. An algorithm developed on images from one database may not perform well as on images from another database (with a different digitization). In this paper, we describe two methods based on a genetic algorithm and a nonlinear algorithm for standardization of digitized and digital mammography. The proposed standardization techniques are based on geometric and intensity transformations that are discovered using a set of calibration images. A set of transformation algorithm is used to search for the best standardization.     

Immunotherapy for Recurrent Pregnancy Loss: Analysis of Results From Clinical Trials

PROBLEM: Up to 80% of unexplained recurrent spontaneous abortions (RS A) are thought to have an immunologic mechanism. Yet clinical trials using immunotherapy to treat women experiencing RSA have low treatment effects. The present study was undertaken to explain the low treatment effects. METHODS: Results of clinical trials using allogeneic leukocyte immunization and intravenous (IV) immunoglobulin (Ig) are compared. The mechanisms of pregnancy loss are reviewed in light of data on frequency of karyotype abnormalities in trophoblast of failing pregnancies. RESULTS: Results of two independent analyses using allogeneic leukocyte immunization as immunotherapy for all women with RSA revealed live birth ratios of 1.16 (P = 0.03) and 1.21 (P = 0.02). When the analysis was limited to primary aborters, the live birth ratio increased to 1.46 (P = 0.006). Live birth ratio after immunotherapy for all RSA using IVIg was 1.88 (P = 0.04). Because of low treatment effects, confounders to treatment success of maternal age and number of previous abortions were studied. Chromosomal abnormalities have been identified in 55% of concepti from RSA. The frequency of chromosomal abnormalities remained constant for up to six pregnancy losses. Women with a history of primary compared to secondary RSA had a higher frequency of karyotypically abnormal concepti (χ² = 4.54, P < 0.05). Risk factors for RSA also include number of previous losses. CONCLUSION: Chromosomal abnormalities are a significant confounder when evaluating efficacy of immunotherapy for treatment of RSA. Some women with RSA have a high risk of recurrent chromosomal problems.     

Collectins and their role in lung immunity

The collectins are a small family of secreted glycoproteins that contain C-type lectin domains and collagenous regions. They have an important function in innate immunity, recognizing and binding to microorganisms via sugar arrays on the microbial surface. Their function is to enhance adhesion and phagocytosis of microorganisms by agglutination and opsonization. In the lung, two members of the collectin family, surfactant proteins A and D, are major protein constituents of surfactant. Another collectin, mannan-binding lectin, is also present in the upper airways and buccal cavity and may protect against respiratory infections. Recent work has shown that collectins have roles in resistance to allergy and in the control of apoptosis and clearance of apoptotic macrophage in the lung.