Genotype prevalence and risk factors for severe clinical adenovirus infection, United States 2004-2006.

BACKGROUND: Recently, epidemiological and clinical data have revealed important changes with regard to clinical adenovirus infection, including alterations in antigenic presentation, geographical distribution, and virulence of the virus. METHODS: In an effort to better understand the epidemiology of clinical adenovirus infection in the United States, we adopted a new molecular adenovirus typing technique to study clinical adenovirus isolates collected from 22 medical facilities over a 25-month period during 2004-2006. A hexon gene sequence typing method was used to characterize 2237 clinical adenovirus-positive specimens, comparing their sequences with those of the 51 currently recognized prototype human adenovirus strains. In a blinded comparison, this method performed well and was much faster than the classic serologic typing method. RESULTS: Among civilians, the most prevalent adenovirus types were types 3 (prevalence, 34.6%), 2 (24.3%), 1 (17.7%), and 5 (5.3%). Among military trainees, the most prevalent types were types 4 (prevalence, 92.8%), 3 (2.6%), and 21 (2.4%). CONCLUSIONS: For both populations, we observed a statistically significant increasing trend of adenovirus type 21 detection over time. Among adenovirus isolates recovered from specimens from civilians, 50% were associated with hospitalization, 19.6% with a chronic disease condition, 11% with a bone marrow or solid organ transplantation, 7.4% with intensive care unit stay, and 4.2% with a cancer diagnosis. Multivariable risk factor modeling for adenovirus disease severity found that age <7 years (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4-7.4), chronic disease (OR, 3.6; 95% CI, 2.6-5.1), recent transplantation (OR, 2.7; 95% CI, 1.3-5.2), and adenovirus type 5 (OR, 2.7; 95% CI, 1.5-4.7) or type 21 infection (OR, 7.6; 95% CI, 2.6-22.3) increased the risk of severe disease.     

Relationship of MMPI cluster type, pain coping strategy, and treatment outcome.

The purposes of the present study of chronic pain patients were to (a) assess whether cognitive and behavioral coping style is related to personality factors, (b) assess how coping styles differ across personality types, and (c) assess how outpatient interdisciplinary intervention affects the coping styles of various personality types. Four MMPI clusters (Depression/Pathological, V-type, Marginal Depression, and Marginal V-type) were derived using a hierarchical clustering procedure. Seventy subjects also completed the Coping Strategies Questionnaire before and after a 3-week outpatient pain management program. Pretreatment analyses indicated the Depression/Pathological and Marginal Depression groups used diverting attention less than either V-type group. The V-type group reported using praying/hoping significantly more than either of the marginal groups. At posttreatment the Depression/Pathological group used catastrophizing significantly more than either of the marginal groups. Results of pre-post analyses indicated that the Depression/Pathological group increased their use of diverting attention, reinterpreting pain sensations, and ignoring pain sensations, while decreasing catastrophizing. The V-type group increased their use of reinterpreting pain sensations, while decreasing praying/hoping and catastrophizing. Neither of the Marginal subtypes showed significant pre-post changes in coping strategies. These results suggest that different personality types use different pain coping strategies prior to multidisciplinary treatment. Groups showing more severe psychological distress, perhaps related to an underlying personality disorder, displayed greater changes in coping strategies with treatment, but remained more dysfunctional after treatment. These findings suggest that the alteration of coping strategies may be an important treatment effect needing more individualization to maximize treatment response.(ABSTRACT TRUNCATED AT 250 WORDS)     

The relationship of gingival crevicular fluid short chain carboxylic acid concentration to gingival inflammation

Abstract Short-chain carboxylic acids (SCCA; C≤5: e.g., lactic acid, propionic acid, butyric acid) are metabolic by-products of bacterial metabolism which accumulate in the gingival crevice, and exhibit significant biological activity, including the ability to alter gene expression. It has been hypothesized that among the activities of SCCAs are their ability to contribute to gingival inflammation. This concept complements the notion that specific periodontal pathogens are the causative agents of gingival inflammation. To begin testing these 2 hypotheses, we examined the relationship between SCCA concentrations, specific putative periodontal pathogens, and gingival inflammation in medically healthy periodontally diseased subjects. We reasoned that if SCCAs and/or specific periodontal pathogens were causative gingival inflammatory agents, gingival inflammation should increase with increasing concentration of the inflammatory mediator. We also recognized that other clinical variables needed to be controlled for, and an objective quantitative assessment of gingival inflammation used. To accomplish these tasks, sites within subjects were stratified by location and pocket depth, and the following quantified: bacteria] presence; SCCA concentration: and gingival inflammation. The results indicated that gingival inflammation directly and significantly correlated with SCCA concentrations in the maxillary and mandibular molars, incisors and canines (all r≥0.47; all p≤ 0.015; too few bicuspids were available for complete analysis). The relationship between gingival inflammation and SCCA concentration was best described by a natural log relationship. Gingival inflammation did not, however, correlate positively with either the total number of specific putative periodontal pathogens, or the sum of subsets of these pathogens (?0.31 ≤r≤ 0.39; 0.08 ≤p 0.75) for any of the locations. Finally, the SCCA concentration did not correlate with the level of individual or groups of pathogens. These data, together with historical work and other preliminary data, support the hypothesis that SCCA, rather than specific putative periodontal pathogens, may be a causative agent in gingival inflammation. This work may, in part, begin to explain the apparent lack of a direct relationship between current gingival inflammation and the prediction of bacterially mediated periodontal attachment loss.     

DNA-based vaccines: new possibilities for disease prevention and treatment.

Ottawa researcher Dr. Heather L. Davis has become a pioneer in the development of DNA-based vaccines. With her collaborators in France and Germany Davis found that introducing the DNA code for the envelope protein of the hepatitis B virus into the muscle tissue of mice prompted a strong and sustained immune response. She believes that DNA-based vaccines could prove to offer many advantages over conventional vaccines, not least of which are greater safety and effectiveness and reduced cost. She has also begun to explore the potential of DNA-based vaccines for use in the treatment of disease. In recent experiments Davis and colleagues in France have successfully used DNA vaccination to cure transgenic mice of a chronic hepatitis B carrier state.     

Selective inhibition of T cell proliferation but not expression of effector function by human alveolar macrophages

BACKGROUND: Alveolar macrophages are thought to play an important part in regulating lung immune responses. While it is clear that human alveolar macrophages suppress T cell proliferation in vitro, the mechanisms by which this is achieved are not clear, nor is it known whether alveolar macrophages also inhibit other aspects of T cell function. METHODS: Peripheral blood mononuclear cells were stimulated with phytohaemagglutinin or house dust mite allergen, and cultured with variable numbers of autologous alveolar macrophages obtained by bronchoalveolar lavage from 20 normal subjects. RESULTS: Alveolar macrophages induced a reversible inhibition of T cell proliferation in response to both mitogen and allergen stimulation, with the latter being considerably more susceptible to inhibition. This was achieved via heterogenous mechanisms, involving both soluble factors derived from alveolar macrophages and cell-cell contact. Despite inhibiting proliferation, alveolar macrophages had little or no effect on T cell calcium flux, the characteristic changes in CD3, CD2, CD28 and interleukin-2 (IL-2) receptor expression which accompany normal T cell activation, and IL-2 and interferon gamma secretion. In contrast, alveolar macrophages inhibited the tyrosine phosphorylation of proteins which may be involved in IL-2 receptor-associated signal transduction. CONCLUSIONS: The immunoregulatory properties of alveolar macrophages are relatively selective, allowing T cell activation and cytokine secretion while inhibiting T cell proliferation within the lung.