The tongue as an alternative donor site for graft urethroplasty: a pilot study

PURPOSE: Urethroplasty with a buccal mucosal graft provides excellent clinical results but it may also cause oral complications in some cases. The mucosa covering the lateral and under surface of the tongue is identical in structure with that lining the rest of the oral cavity. We evaluated LMGs for urethroplasty. MATERIALS AND METHODS: From January 2001 to September 2004, 8 men 34 to 65 years old (mean age 46.1) with urethral strictures 1.5 to 4.5 cm long were selected for 1-stage dorsal onlay urethroplasty. The site of the harvest graft was the lateral mucosal lining of the tongue. Postoperatively all patients were followed with urethrography, uroflowmetry, cystourethrography and flexible urethroscopy after 3 and 12 months. Successful reconstruction criteria were peak flow rate greater than 15 ml per second and no need for postoperative urethral dilation. RESULTS: Median followup was 18 months (mean 22.1, range 3 to 47). Seven cases were successful. One patient had a partial urethral stricture. In successful cases cystourethrography revealed no significant graft contractures or sacculations and at flexible urethroscopy LMG was almost indistinguishable from native urethra. There were no pain, esthetic or functional complications at the donor site. CONCLUSIONS: Harvesting the LMG is feasible and easy to perform. Compared with the buccal mucosal graft the LMG seems to be associated with less postoperative pain and a minor risk of donor site complications. These preliminary functional and esthetic data are satisfactory.     

Hepatocyte growth factor effects on mesenchymal stem cells: proliferation, migration, and differentiation

Hepatocyte growth factor (HGF), a pleiotropic cytokine of mesenchymal origin promoting migration, proliferation, and survival in a wide spectrum of cells, can also modulate different biological responses in stem cells, but the mechanisms involved are not completely understood so far. In this context, we show that short-term exposure of mesenchymal stem cells (MSCs) to HGF can induce the activation of its cognate Met receptor and the downstream effectors ERK1/2, p38MAPK, and PI3K/Akt, while long-term exposure to HGF resulted in cytoskeletal rearrangement, cell migration, and marked inhibition of proliferation through the arrest in the G1-S checkpoint. When added to MSCs, the K252A tyrosine kinase inhibitor prevented HGF-induced responses. HGF's effect on MSC proliferation was reversed by p38 inhibitor SB203580, while the effects on cell migration were abrogated by PI3K inhibitor Wortmannin, suggesting that HGF acts through different pathways to determine its complex effects on MSCs. Prolonged treatment with HGF induced the expression of cardiac-specific markers (GATA-4, MEF2C, TEF1, desmin, alpha-MHC, beta-MHC, and nestin) with the concomitant loss of the stem cell markers nucleostemin, c-kit, and CD105.     

Accuracy of monoclonal stool antigen test for the diagnosis of H. pylori infection: a systematic review and meta-analysis

OBJECTIVE: To perform a systematic review and a meta-analysis of accuracy of monoclonal stool antigen test (SAT) for the diagnosis of Helicobacter pylori infection. METHODS: Selection of studies: assessing the accuracy of monoclonal SAT for the diagnosis of H. pylori infection. Search strategy: electronic and manual bibliographical searches. Data extraction: independently done by two reviewers. Data synthesis: meta-analyses combining the sensitivities, specificities, and likelihood ratios (LRs) of the individual studies. RESULTS: Twenty-two studies, including 2,499 patients, evaluated the monoclonal SAT before eradication therapy. Pooled sensitivity, specificity, LR+, and LR- were: 0.94 (95% CI 0.93-0.95), 0.97 (0.96-0.98), 24 (15-41), and 0.07 (0.04-0.12). The accuracy of both monoclonal and polyclonal SAT was evaluated together in 13 pretreatment studies, and higher pooled sensitivity was demonstrated with the monoclonal technique (0.95 vs 0.83). Twelve studies, including 957 patients, assessed the monoclonal SAT to confirm eradication after therapy. Pooled sensitivity, specificity, LR+, and LR- were 0.93 (0.89-0.96), 0.96 (0.94-0.97), 17 (12-23), and 0.1 (0.07-0.15). Both tests were evaluated together in eight post-treatment studies and, again, the monoclonal technique showed higher sensitivity (0.91 vs 0.76). Heterogeneity among studies disappeared when a single outlier study was excluded. Subanalysis depending on the reference method, the study population, or the study quality showed similar results. CONCLUSION: Monoclonal SAT is an accurate noninvasive method both for the initial diagnosis of H. pylori infection and for the confirmation of its eradication after treatment. The monoclonal technique has higher sensitivity than the polyclonal one, especially in the post-treatment setting.     

Standardization and performance evaluation of mononuclear cell cytokine secretion assays in a multicenter study

Background

Burkholderia pseudomalleiis the causative agent for melioidosis. For many bacterial infections, cytokine dysregulation is one of the contributing factors to the severe clinical outcomes in the susceptible hosts. The C57BL/6 and BALB/c mice have been established as a differential model of susceptibility in murine melioidosis. In this study, we compared the innate IFN-γ response toB. pseudomalleibetween the C57BL/6 and BALB/c splenocytes and characterized the hyperproduction of IFN-γ in the relatively susceptible BALB/c micein vitro.

Results

Naïve BALB/c splenocytes were found to produce more IFN-γ in response to live bacterial infection compared to C57BL/6 splenocytes. Natural killer cells were found to be the major producers of IFN-γ, while T cells and Gr-1^intermediatecells also contributed to the IFN-γ response. Although anti-Gr-1 depletion substantially reduced the IFN-γ response, this was not due to the contribution of Gr-1^high, Ly-6G expressing neutrophils. We found no differences in the cell types making IFN-γ between BALB/c and C57BL/6 splenocytes. Although IL-12 is essential for the IFN-γ response, BALB/c and C57BL/6 splenocytes made similar amounts of IL-12 after infection. However, BALB/c splenocytes produced higher proinflammatory cytokines such as IL-1β, TNF-α, IL-6, IL-18 than C57BL/6 splenocytes after infection withB. pseudomallei.

Conclusion

Higher percentages of Gr-1 expressing NK and T cells, poorer ability in controlling bacteria growth, and higher IL-18 could be the factors contributing to IFN-γ hyperproduction in BALB/c mice.     

Failure to read motor intentions from gaze in children with autism

A core feature of autism is the abnormal use of gaze to attribute mental states to others, and thus to predict others' behaviour. An untested idea is whether this dysfunction is confined to mental states having a propositional content, such as beliefs and desire or extends to motor intentional states which allow one to make inferences about the actions of others. This study used kinematics to examine the ability to use gaze to inform one about the motor states of another in normal and autistic children. In each trial two participants, a model and an observer, were seated facing each other at a table. In three experimental blocks the model was requested to grasp a stimulus, to gaze towards the same stimulus, and to gaze away from the stimulus without performing any action. The task for the observer was to grasp the stimulus after having watched the model perform her task. We observed that normal children showed facilitation effects in terms of movement speed following the observation of the model grasping or simply gazing at the object. In contrast, autistic children did not show any evidence of facilitation in these conditions. Neither normal nor autistic children showed evidence of facilitation when the model's gaze was not directed towards the stimulus. These findings demonstrate that, in contrast to normal children, children with autism fail to use information from the model's action or gaze to plan their subsequent action, and that in autism the inability to use of another person's gaze produces a lack of understanding of the motor intention of others.     

Short-Term Effects of Nitrogen Dioxide on Mortality and Susceptibility Factors in 10 Italian Cities: The EpiAir Study

Background: Several studies have shown an association between nitrogen dioxide (NO₂) and mortality. In Italy, the EpiAir multicentric study, “Air Pollution and Health: Epidemiological Surveillance and Primary Prevention,” investigated short-term health effects of air pollution, including NO₂.Objectives: To study the individual susceptibility, we evaluated the association between NO₂ and cause-specific mortality, investigating individual sociodemographic features and chronic/acute medical conditions as potential effect modifiers.Methods: We considered 276,205 natural deaths of persons > 35 years of age, resident in 10 Italian cities, and deceased between 2001 and 2005. We chose a time-stratified case-crossover analysis to evaluate the short-term effects of NO₂ on natural, cardiac, cerebrovascular, and respiratory mortality. For each subject, we collected information on sociodemographic features and hospital admissions in the previous 2 years. Fixed monitors provided daily concentrations of NO₂, particulate matter ≤ 10 μm in aerodynamic diameter (PM₁₀) and ozone (O₃).Results: We found statistically significant associations with a 10-μg/m³ increase of NO₂ for natural mortality [2.09% for lag 0–5; 95% confidence interval (CI), 0.96–3.24], for cardiac mortality (2.63% for lag 0–5; 95% CI, 1.53–3.75), and for respiratory mortality (3.48% for lag 1–5; 95% CI, 0.75–6.29). These associations were independent from those of PM₁₀ and O₃. Stronger associations were estimated for subjects with at least one hospital admission in the 2 previous years and for subjects with three or more specific chronic conditions. Some cardiovascular conditions (i.e., ischemic heart disease, pulmonary circulation impairment, heart conduction disorders, heart failure) and diabetes appeared to confer a strong susceptibility to air pollution.Conclusions: Our results suggest significant and likely independent effects of NO₂ on natural, cardiac, and respiratory mortality, particularly among subjects with specific cardiovascular preexisting chronic conditions and diabetes.     

Uncommon yeast infections in hematological patients: from diagnosis to treatment

Invasive fungal diseases have been recognized with increasing frequency as major pathogens in patients with cancer over the past few decades, as a result of new and more aggressive anticancer treatments and supportive care, and this has been especially reported for patients suffering from hematological malignancies. In these settings, typically uncommon yeasts and filamentous fungi have recently emerged as significant human pathogens, frequently as breakthrough infections in patients receiving empirical antifungal therapy or antifungal prophylaxis and with reported high crude mortality rates. The aim of this article is to discuss certain aspects of the approach to invasive fungal diseases due to uncommon yeasts (e.g., Trichosporon spp., Blastomyces spp. and Cryptococcus spp.) in patients with hematological malignancies, focusing on epidemiology, diagnosis, treatment outcomes and the role of novel antifungal drugs (i.e., new triazoles and echinocandins).