Predictive factors in the response to interferon therapy in chronic hepatitis C

Factors predicting the efficacy of interferon therapy were statistically analyzed on 111 patients with chronic hepatitis C. Of the treated patients (total doses of interferon; 96–468 MU), 35 (31.5%) had a long-term remission. On multivariate analysis, hepatitis C virus genotype (p<0.0001), histological diagnosis (p<0.05), fibrosis score of histological activity index (p<0.01) and source of infection (p<0.05) were found useful for predicting the response to interferon therapy. Our findings suggest that the outcome of interferon therapy can be predicted to some degree from pretreatment data, and that a new therapeutic strategy is necessary for the group of patients who are predicted to be nonresponders.     

Impairment of angiogenic activity in the serum from patients with coronary aneurysms due to Kawasaki disease.

BACKGROUND: The inflammatory mediators play an important role in the progression of coronary vasculitis in Kawasaki disease (KD), but effects of KD serum including inflammatory mediators on endothelial cells remain unknown. We hypothesized that serum activity to stimulate in vitro human umbilical vein endothelial cells (HUVEC) tube formation might be impaired in KD. METHODS AND RESULTS: Serum from patients with coronary aneurysms was less active in stimulating HUVEC tube formation than serum from patients without coronary aneurysms or febrile controls. In patients with coronary aneurysms, the reduction in the serum angiogenic activity was documented already before KD treatment (p=0.03 vs healthy controls, p=0.08 vs febrile controls) and enhanced after intravenous immune globulin plus aspirin (p<0.001 vs healthy controls, p=0.002 vs febrile controls); both drugs did not affect the assay studied. This reduction was greater in patients who later developed giant aneurysms >8 mm compared with those who developed small to moderate aneurysms (p=0.01). The reduced serum angiogenic activity was partly caused by the reduction in the serum activity of stimulating HUVEC proliferation. CONCLUSIONS: Serum activity to stimulate HUVEC tube formation was impaired in KD patients who later developed larger coronary aneurysms, which may be associated with the severity of vascular injury.     

Human-animal anthrax outbreak in the Luangwa valley of Zambia in 2011

There has been a reduction of incidences of anthrax in the developed countries but it is still a public health problem in the developing countries where communities live in interface areas with wildlife. An outbreak of anthrax in Hippopotamus amphibious was observed in Zambia. Following the death of hippopotamuses, suspected human cases were reported. The objective of this study was to isolate and confirm Bacillus anthracis and to determine the antimicrobial susceptibility for the management of the disease. Of the specimens collected, 29.4% (95% confidence interval [CI], 11.4-56.0) were from humans, 42.1% (95% CI, 21.1-66.0) were from hippopotamuses and 20.0% (95% CI, 6.61-44.3) from the soil were found to be positive were for B. anthracis. An antimicrobial susceptibility test revealed that all the isolates were found to be sensitive to the recommended antibiotics. The disease control was achieved by case management and by explaining to the communities that they should avoid contact with animals that die from unknown causes.     

Negative effects of GM-CSF signaling in a murine model of t(8;21)-induced leukemia

The t(8;21)(q22;q22) is common in adult acute myeloid leukemia (AML). The RUNX1-ETO fusion protein that is expressed by this translocation is poorly leukemogenic and requires additional mutations for transformation. Loss of sex chromosome (LOS) is frequently observed in t(8;21) AML. In the present study, to evaluate whether LOS cooperates with t(8;21) in leukemogenesis, we first used a retroviral transduction/transplantation model to express RUNX1-ETO in hematopoietic cells from XO mice. The low frequency of leukemia in these mice suggests that the potentially critical gene for suppression of t(8;21) leukemia in humans is not conserved on mouse sex chromosomes. The gene encoding the GM-CSF receptor α subunit (CSF2RA) is located on X and Y chromosomes in humans but on chromosome 19 in mice. GM-CSF promotes myeloid cell survival, proliferation, and differentiation. To determine whether GM-CSF signaling affects RUNX1-ETO leukemogenesis, hematopoietic stem/progenitor cells that lack GM-CSF signaling were used to express RUNX1-ETO and transplanted into lethally irradiated mice, and a high penetrance of AML was observed in recipients. Furthermore, GM-CSF reduced the replating ability of RUNX1-ETO-expressing cells. These results suggest a possible tumor-suppressor role of GM-CSF in RUNX1-ETO leukemia. Loss of the CSF2RA gene may be a critical mutation explaining the high incidence of LOS associated with the t(8;21)(q22;q22) translocation.     

Effects of light emitting diode (LED) therapy at 940 nm on inflammatory root resorption in rats

The effects of LED therapy at 940 nm on periodontal healing, inflammatory cell infiltration, and root resorption were analyzed in an experimental model of orthodontic tooth movement in rats. Twenty-five male Wistar rats were allocated into four experimental groups: Control animals (Co, n?=?5), Controls + LED therapy (CoLED, n?=?6), animals submitted to orthodontic force (RR, n?=?7) and submitted to orthodontic force + LED therapy (RRLED, n?=?7). All procedures were approved by the Committee for Ethics in Animal Experimentation of the Universidade Estadual de Londrina (protocol CEEA 5/2010 37359). A force of 50 g was applied to the right upper molars of RR and RRLED groups. On days 2, 3, and 4 after orthodontic treatment, the CoLED and RRLED groups received LED irradiation (940 nm, 4 J/cm²). The animals were killed on day 7 for histological analysis. An increased number of root resorption lacunae was found only in the RR group (p?<?0.05). The RR group also presented more osteoclasts (p?<?0.005) and inflammatory cell infiltration (p?<?0.005) than the control group. The RRLED group presented fewer osteoclasts (p?<?0.005) and inflammatory cells (p?<?0.005) in the periodontal ligament than the RR group. The CoLED and RRLED groups presented more periodontal fibroblasts (p?<?0.005) than non-irradiated groups. RRLED presented more blood vessels (p?<?0.01) in the periodontal ligament than the RR group. In conclusion, the results suggest that LED therapy improved periodontal tissue repair and decreased inflammation and root resorption after the application of orthodontic force.     

Cost-effectiveness of tobacco control policies in Vietnam: the case of personal smoking cessation support

Aims To examine the cost‐effectiveness of personal smoking cessation support in Vietnam. Design, setting and participants We followed‐up the population aged 15 years and over in 2006 to model the costs and health gains associated with five interventions: physician brief advice; nicotine replacement therapy (patch and gum); bupropion; and varenicline. Threshold analysis was undertaken to determine the price levels of pharmaceuticals for the interventions to be cost‐effective. A multi‐state life table model was constructed such that the interventions affect the smoking cessation behaviour of the age cohorts, and the resulting smoking prevalence defines their health outcomes. A health‐care perspective was employed. Measurements Cost‐effectiveness is measured in 2006 Vietnamese Dong (VND) per disability‐adjusted life year (DALY) averted. We adopted the World Health Organization thresholds of being ‘cost‐effective’ if less than three times gross domestic product (GDP) per capita (VND 34 600 000) and ‘very cost‐effective’ if less than GDP per capita (VND 11 500 000). Findings The cost‐effectiveness result of physician brief advice was VND 1 742 000 per DALY averted (international dollars 543), which was ‘very cost‐effective’. Varenicline dominated bupropion and nicotine‐replacement therapies, although it did not fall within the range of being ‘cost‐effective’ under different scenarios. The threshold analysis revealed that prices of pharmaceuticals must be substantially lower than the levels from other countries if pharmacological therapies are to be cost‐effective in Vietnam. Conclusions Physician brief advice is a cost‐effective intervention and should be included in the priority list of tobacco control policy in Vietnam. Pharmacological therapies are not cost‐effective, and so they are not recommended in Vietnam at this time unless pharmaceuticals could be produced locally at substantially lower costs in the future.