What is the place of genetics in the pathogenesis of pre-eclampsia?

It is most unlikely that there is a single 'pre-eclampsia (PE) gene'. We are probably looking for a cluster of polymorphisms which, possibly in conjunction with environmental factors, predispose to the development of the condition. Accurate phenotyping is vital for any genetic studies of PE, and since the disease is only clinically-detectable in the second half of pregnancy, is particularly difficult. It is increasingly likely that there is a fetal genetic contribution which can only be examined after birth. Candidate genes examined on the basis of displayed or hypothetical pathophysiological effects, but for which no evidence of association or linkage has been found have included HLA-DRbeta, HLA-G, and tumour necrosis factor alpha (chromosome 6), angiotensin-converting enzyme (chromosome 17) and CuZn superoxide dismutase (chromosome 21). Chromosomal exclusion mapping and a pedigree study suggest a role for genes on chromosomes 1, 3, 4, 9 or 18. Two genes concerned with clotting, those for factor 5 and methylenetetrahydrofolate reductase, lie on chromosome 1. Both have polymorphisms present in significantly higher frequency in women with PE, as well as showing functional abnormality. They probably predispose to the development of the condition, without being necessary for it. The angiotensinogen (Aogen) gene also lies on chromosome 1. The renin-angiotensin system may be activated during the early stages of PE and subsequently suppressed. In some populations, a relatively common polymorphism is present in raised frequency in women with PE, but it is also raised in non-pregnant hypertensive subjects. However, it is in partial linkage disequilibrium with another polymorphism which shows significantly distorted transmission from mother to fetus in PE pregnancies. Furthermore, its expression is significantly raised in the decidual spiral arteries; abnormal placentation is a feature of PE. We have also shown that a relatively common polymorphism in the angiotensin AT1 receptor gene (chromosome 3) is associated with raised density of the receptor. Thus far, studies of candidate genes have been on a small scale and have very much reflected the pathophysiological research interests of the investigators. The multifaceted nature of PE and the difficulties of accurate phenotyping require the accumulation of a large, very carefully phenotyped, database. It is hoped that funding will become available this year in the UK to allow the collection of such a database. The introduction of chip technology should allow genome scanning of the resource.     

What is the purpose of launching the World Journal of Clinical Pediatrics?

The first issue of the World Journal of Clinical Pediatrics (WJCP), whose preparatory work was initiated on January 10, 2011, will be published on June 8, 2012. The WJCP editorial board has now been established and consists of 100 distinguished experts from 31 countries. Our purpose of launching the WJCP is to publish peer-reviewed, high-quality articles via an open-access online publishing model, thereby acting as a platform for communication between peers and the wider public, and maximizing the benefits to editorial board members, authors and readers.     

What is new in the management of childhood asthma?

The prevalence of asthma has increased in developed countries. The efficacy of available drugs in those with severe persistent disease is limited. This has led to a renewed search for the reasons for failures of the existing treatment and for novel concepts. Treatment with inhaled corticosteroids, and to a much lesser extent theophylline, can reduce the survival of inflammatory cells including esinophils. Emerging trends in treatments for asthma could include strategies to alter the cytokine/chemokine balance. It is evident that the current ICS are already very efficient and safe, it will be difficult to introduce further improved formulations. Perhaps the most fruitful effort shall be in developing patient friendly easy to use targeted delivery systems. The newer therapies are planned for the several upstream targets and may have potential to prevent the disease. Various potential therapies are being worked upon like-targeting prevention of T cell activation, modulation of Th-1/Th-2 differentiation, inhibition of Th-2 related cytokines, Th-1/Th-2 modulation, inhibition of downstream mediators etc. The new strategy shall perhaps lie with matching the patients and their disease with the most suitable therapy.     

What is New in the Management of Childhood Asthma?

Asthma still causes considerable morbidity and mortality globally and minimal improvement has been seen in key outcomes over the last decade despite increasing treatment costs. This review summarizes recent advances in the management of asthma in children and adolescents. It focuses on the need for personalized treatment plans based on heterogenous asthma pathophysiology, the use of the terminology ‘asthma attack’ over exacerbation to instill widespread understanding of severity, and the need for every attack to trigger a structured review and focused strategy. The authors discuss difficulties in diagnosing asthma, accuracy and use of Fractional exhaled nitric oxide both as second line test and as a method to monitor treatment adherence or guide the choice of pharmacotherapy. The authors discuss acute and long-term management of asthma. Asthma treatment goals are to minimize symptom burden, prevent attacks and (where possible) reduce risk and impact of progressive pathophysiology and adverse outcomes. The authors discuss pharmacological management; optimal use of short acting β₂ agonists, long acting muscarinic antagonist (tiotropium), use of which is relatively new in pediatrics, allergen specific immunotherapy, biological monoclonal antibody treatment, azalide antibiotic azithromycin, and the use of vitamin D. They also discuss electronic monitoring and adherence devices, direct observation of therapy via mobile device, temperature controlled laminar airflow device, and the importance of considering when symptoms may actually result from dysfunctional breathing rather than asthma.     

What is the role of the prevention of allergy in the first period of life?

The widespread increase in the prevalence of allergic disease, which has occurred over the last 20 y, has created general concern in Europe and in the rest of the world. The reason for this increase is still partially unknown. In this period, despite a greater understanding of the pathogenesis and risk factors of allergies plus the greater efficacy of drugs to control the symptoms, the cost of intervention and the socio-economic impact are still very high. For these reasons, prevention in the first period of life represents a goal for both developed and developing countries in order to reduce this upward trend.     

What is the impact of outdoor pollution on children's asthma?

Outdoor pollution is a complex mix of more than 200 air contaminants. Among these pollutants, ozone, nitrogen dioxide and fine particles may generate bronchial inflammation and hyperreactivity. The hypothesis that pollution contributes to the development of asthma in children is based on epidemiological, clinical and experimental data. Many risk factors during the in utero and postnatal period have been identified in the aetiology of childhood asthma. During pregnancy, outdoor pollution was identified as a causal factor of respiratory disease in neonatal cohort studies. Several epidemiological studies also demonstrate that outdoor pollution is a trigger of asthma exacerbations. This review aims to highlight the current knowledge on outdoor pollution and asthma.     

What is the intrapatient variability of mycophenolic acid trough levels?

TDM of MPA, the active compound of MMF, is rarely used despite its substantial intra‐ and interpatient variability. Little is known about the utility of long‐term MPA TDM. Data are expressed as mean (one standard deviation). All available data from 27 renal transplant recipients (mean age at transplantation: 7.7 [5.0] yr) with an average follow‐up of 9.3 (4.6) yr were analyzed. MPA levels were measured using the EMIT. GFR was measured using cystatin C and eGFR was calculated using the Filler formula. Intrapatient CV of the trough level was calculated as the ratio of the mean divided by one standard deviation. Mean cystatin C eGFR was 56.9 (24.4) mL/min/1.73 m². There was a weak but significant correlation between the MPA trough level and the AUC (Spearman r = 0.6592, p < 0.0001). A total of 1964 MPA trough levels (73 [45]/patient) were measured, as compared to 3462 Tac trough levels (144 [71]/patient). The average MPA trough level was 3.01 (1.26) mg/L and the average trough Tac level was 7.3 (1.8) ng/mL. Intrapatient CV was statistically higher (p = 0.00093) for MPA at 0.68 (0.29) when compared to Tac with a CV of 0.46 (0.12). CV did not correlate with eGFR. Intrapatient MPA trough level CV is significantly higher than for Tac, while CV for both MPA and Tac was high. MPA trough level monitoring may be a feasible monitoring option to improve patient exposure and possibly outcomes.     

What is the importance of bacterial eradication in the treatment of respiratory tract infections?

During the last few years, increasing antibiotic resistance amongst the major respiratory pathogens in the community has compromised the choice of empirical therapy for some respiratory tract infections. Of special interest has been the progressive increase in the resistance rates of Streptococcus pneumoniae to macrolides and penicillin, and of S. pyogenes to macrolides. Several studies have confirmed the association between community use of certain antibiotics and the development of resistance in S. pneumoniae and S. pyogenes. Nevertheless, not all the antibiotics have the same ability to select resistance and not all microorganisms are affected in the same way. The aim of antimicrobial therapy in respiratory tract infections is bacterial eradication. Pharmacokinetic and pharmacodynamics can be used to predict bacteriological eradication with antimicrobial therapy.