High prevalence of the CD14-159CC genotype in patients infected with severe acute respiratory syndrome-associated coronavirus

To investigate whether genetic factors of innate immunity might influence susceptibility and/or progression in individuals infected with SARS, we evaluated the CD14 gene polymorphism in 198 Hong Kong blood donors and 152 Hong Kong severe acute respiratory syndrome (SARS) patients who were previously genotyped for FcγRIIA polymorphisms. The prevalence of the CD14-159CC polymorphism was significantly higher in the patients with severe SARS than in the those with mild SARS or controls (31% versus 15% [mild SARS] or 20% [controls]; mild SARS: P = 0.029; odds ratio, 2.74; 95% confidence interval, 1.15 to 6.57; controls, P = 0.04; odds ratio, 2.41; 95% confidence interval, 1.05 to 5.54), and both CD14-159CC and FcγRIIA-RR131 are risk genotypes for severe SARS-CoV infection.     

The timing of sulfadiazine therapy impacts the reactivation of latent Toxoplasma infection in IRF-8−/− mice

The process of reactivation of latent infection with Toxoplasma gondii in immunosuppressed hosts is yet not fully understood. In the past, a number of murine models of reactivation in immunocompromised mice have been described using sulfadiazine to establish latent infection before withdrawal and subsequent reactivation. We studied the process of reactivation in brains of mice with a targeted mutation in the interferon-regulatory factor (IRF)-8 gene after withdrawal of sulfadiazine therapy. IRF-8^−/− mice were orally infected with five cysts of the ME 49 strain of T. gondii. To allow establishment of latent infection with cyst formation, mice were treated with sulfadiazine starting either 3, 5, 6, or 7 days postinfection. Sulfadiazine was withdrawn after 14–21 days to allow reactivation. We observed that timing of sulfadiazine therapy had a marked impact on the course of infection and reactivation. Mice treated late after infection (days 5–7) showed increased mortality and decreased time to death compared to mice treated early after infection (group A). In the blood of mice with late (days 5–7) but not early (day 3) initiation of treatment, T. gondii-specific deoxyribonucleic acid was detected by polymerase chain reaction. Using double staining with stage-specific antibodies, tachyzoites were detectable in brains of mice with late initiation of sulfadiazine treatment but rarely within cysts thus indicating continued invasion of parasites across the blood–brain barrier. Intracerebral cyst rupture or bradyzoite–tachyzoite conversion was not detectable in IRF-8^−/− mice when sulfadiazine therapy was initiated late after infection. These results indicate that continued invasion of tachyzoites rather than reactivation of latent cerebral infection impacts the course of infection in this model of reactivated toxoplasmosis. In conclusion, the timing of sulfadiazine therapy is of utmost importance for the course of infection in immunocompromised mice.     

The effects of COX-2 selective and non-selective NSAIDs on the initiation and progression of atherosclerosis in ApoE−/− mice

In this study, we investigated the effects of prolonged administration of the selective COX-2 inhibitors celecoxib and rofecoxib and the non-selective NSAID naproxen on the initiation and progression of atherosclerosis. ApoE(-/-) mice, as well as corresponding wild-type mice, were fed either a normal chow or a high fat Western diet with or without addition of the respective drugs over a period of 16 weeks. Thereafter, aortic lesion size, plasma lipid levels, and COX-2 expression in the plaques were determined. The results showed that neither the COX-2 selective inhibitors nor naproxen had a significant impact on the initiation and progression of atherosclerosis in diet-fed ApoE(-/-) mice, although both celecoxib and rofecoxib showed a tendency to reduce plaque size. This slight effect may be due to selective inhibition of COX-2 activity because the COX-2 expression was not altered in the plaque. Plasma lipid levels were also not significantly influenced by these drugs. Interestingly, in ApoE(-/-) mice that have been fed with normal chow, we found an increased incidence of plaque formation after treatment with celecoxib and rofecoxib, indicating that coxibs may promote the initiation of atherosclerosis. This effect was probably masked in diet-fed mice by the more pronounced effects of the high cholesterol diet. In conclusion, the reduction in diet-induced plaque size in animals fed a high fat diet and the promotion of atherosclerosis in mice on a normal diet indicate a dual role of the coxibs. In advanced stages of atherosclerosis, they may exert antithrombotic properties due to their COX-2 inhibiting activity, whereas in very early stages they may favor the initiation of atherogenesis. However, because these results were only observed in ApoE(-/-) and not in wild-type animals, coxibs may increase the risk of thrombosis in patients with a predisposition for thrombotic complications.     

From cure to palliation: agreement, timing, and decision making within the staff

Important issues in the transition from curative treatment to palliative care are agreement, timing, and decision making. A survey of 309 nurses and 415 physicians in Sweden showed that 61% of the nurses and 83% of the physicians thought agreement was current practice. None said that the decisions were made too early, but 19% of the nurses and 14% of the physicians thought that they often were made too late. Very few respondents stated that such decisions are changed, 0% and 1%, respectively. More than half of the informants made detailed comments on such transitions indicating that awareness and flexibility are desirable to make well-informed decisions. Three themes that emerged from the analysis concerning the decision to stop curative treatment and focus on palliative care were that the staff members should (if possible) make such decisions in agreement and should sometimes make the decisions earlier and that well-based reasons are required to make changes.     

Fixed combination of losartan and hydrochlorothiazide and reduction of risk of stroke

A fixed-dose combination of losartan/hydrochlorothiazide (HCTZ) therapy may be a logical choice for antihypertensive treatment, including for initial therapy in patients with blood pressure elevation >20/10 mmHg above treatment target. The renin-angiotensin-aldosterone-system-activating effect of hydrochlorothiazide augments the efficacy of blocking the angiotensin II type 1 (AT1) receptor with losartan. Some adverse effects associated with hydrochlorothiazide, including increased risk for new-onset diabetes mellitus, may be offset by losartan. Losartan was frequently administered with hydrochlorothiazide in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, in which there was a 25% risk reduction for stroke in the losartan-based compared with the atenolol-based treatment group. The efficacy, tolerability, and convenience of losartan/HCTZ combination therapy may increase patient compliance and lower risk for stroke, a devastating outcome in patients with hypertension.     

Plasma B vitamins and their relation to the severity of chronic heart failure

BACKGROUND: Total homocysteine (tHcy) has been linked to the severity of chronic heart failure (CHF). Elevated tHcy concentrations are mainly caused by folate and vitamin B-12 deficiencies. OBJECTIVE: We hypothesized that folate and vitamin B-12 deficiencies can explain the relation between tHcy and the severity of CHF. DESIGN: We investigated 987 CHF patients. All subjects underwent a physical examination and blood sampling. Cardiac catheterization was performed in 929 patients and echocardiography in 460 patients. Serum tHcy, folate, vitamin B-12, and N-terminal pro-B-type natriuretic-peptide (NT-proBNP) were measured and renal and hepatic function were studied. RESULTS: tHcy increased with increasing New York Heart Association (NYHA) classes of heart failure (P < 0.001) and correlated with the left ventricular ejection fraction (EF; r = -0.150, P < 0.001). Contrary to the hypothesis, vitamin B-12 (P < 0.001) increased with NYHA class (P < 0.001) and was negatively correlated with EF (r = -0.080, P = 0.015). Folate showed no relation with NYHA class or EF. Comparable results were obtained for NT-proBNP (tHcy: r = 0.27, P < 0.001; vitamin B-12: r = 0.091, P = 0.004; folate: r = -0.045, P = 0.169). The correlations between tHcy, EF, and NT-proBNP were significantly stronger in patients without coronary artery disease (CAD) than in those with CAD. Regression analysis showed that tHcy, but not B vitamins, is a strong predictor of EF and NT-proBNP. CONCLUSIONS: This study showed that tHcy, but not folate and vitamin B-12, is related to clinical, echocardiographic, and laboratory variables of CHF, which indicates a relation between tHcy and the severity of CHF. This relation is stronger in patients without CAD. The lack of association of folate and the paradoxical relation of vitamin B-12 with CHF can possibly be explained by a disturbance in hepatic homeostasis.     

Red reflex: prevention way to blindness in childhood

This study had as objective to investigate the result and the colour gradation of red reflex test in newborns (NB). It is a exploratory, quantitative study and the sample was 180 NB from maternity ward in Fortaleza-CE. From this, 156 showed result "no altered" and 24 "suspect". About the aspect of red reflex, 144 NB showed the same coloration in the two eyes, in 35 of this, the colour was red, in 33, orange reddish, in 46 orange colour, in 24 light yellow, in 6 yellow with whitish stains central. Of the suspect cases, the reflex was light yellow with whitish stains with lines. The nurse trained to accomplish the red reflex test can have important role at Neonatal Unit with actions about the prevention of ocular alterations in the childhood.     

Comprehensive quality assessment of healthy school interventions

OBJECTIVES: The number of healthy school interventions of unknown quality overwhelms schools. Quality is a construct that is differently interpreted by teachers and health promoters. The schoolBeat checklist for quality assessment of healthy school interventions incorporates the quality perceptions of both professional groups. To support quality improvements - and thus effectiveness - in school health promotion, this study evaluates the schoolBeat checklist. METHODS: Twenty-nine healthy school interventions were assessed in the Netherlands, each by two health promoters and two teachers-individually and at a consensus meeting. Generalizability coefficients were calculated for the nine specific quality criteria. RESULTS: The mean consensus score differs from the mean average individual score for two out of nine criteria. To obtain a threshold Generalizability coefficient of 0.70, the number of assessors required per criterion ranges from 1.6 to 10.8, with an average of 4.7. CONCLUSION: Quality assessment procedures of healthy school interventions using the schoolBeat checklist require about four experienced assessors from each professional domain to facilitate reliable quality scores based on individual assessment only. Publicly available quality scores enable the inclusion of high quality interventions in school policies in order to increase the impact of school health.