Current Pediatric Reviews - Volume 2, Issue 2, 2006

Cystic fibrosis is a monogenic disorder with significant morbidity and mortality, despite advances in conventional treatment. It is a good candidate for gene therapy and this field has progressed rapidly since the cystic fibrosis transmembrane conductance regulator gene was cloned. We will review the specific questions to address for successful cystic fibrosis gene therapy, such as the extra- and intracellular barriers to airway gene transfer, the target cells and the endpoints to assess efficacy. We will discuss recent advances in viral and nonviral gene transfer agents, delivery techniques and novel strategies to enhance airway gene transfer and expression.

Once the genetic defect of cystic fibrosis (CF), the most common autosomal recessive disease, was discovered, there was hope for quick positive results with gene-therapy. These did not came true, however. Recent CF mice studies by Freedman et al. demonstrated a disease reversal by high doses of docosahexaenoic acid (DHA). Although it is known for long that the same essential fatty acid imbalance with low levels of DHA is present in CF patients and that DHA has antiinflammatory actions, caution is urged to prevent false expectations when we extrapolate mice model results. This review explores the present scientific data on DHA supplementation in CF.

Nutrition is age specific, in all aspects. The intake of young children depends on their caretakers. It is obvious that growth and development cause major changes in children. However, these changes not only consider size but also body composition and maturation of many (digestive) functions. Energy and nutrient requirements do not only depend on intake, but also on expenditure. The latter depends on many variables such as physical activity. Physiological needs for calories differ according to age. Also the needs for macro- and micronutrients are age-dependent. As a consequence, it is impossible to deduce recommendations for children from adult data. Because of changing physical activity, and because of errors in earlier techniques to measure intake and expenditure, recommendations for energy intake may have to be updated.

Infection with Neisseria meningitidis remains one of the most devastating illnesses in pediatrics. Affected patients can progress from a mild viral-like illness to death within a matter of hours. Additionally, the definitive clinical diagnosis cannot be reached until the characteristic petechial rash appears, making differentiating meningococcal infection from a benign viral illness impossible. This review will discuss the epidemiology, bacteriology, pathophysiology, treatment, and potential new therapies for severe meningococcal infections in children and adolescents.

Hypoxia-ischemia is responsible for a high morbidity and mortality rate, both in infant and adult patients. In humans, the brain is immature from fetal to postnatal life, demonstrating more specific vulnerability than the adult one, induced by exposure at perinatal asphyxia. The extension and distribution of brain lesions depend to a large extent on the intensity and exposure to injury, the maturational stage, the affected brain region and the survival time of the patient. Different cellular events are developed in response to hypoxic-ischemic injury. These events have been related to the excitotoxicity (activation of glutamate receptors), energy failure (decrease in ATP levels), inflammatory cascade (delivery of inflammatory mediators), and gene and transcriptional activation.

Developmental delay (DD) is a commonly encountered clinical problem. Nearly most children with neurodevelopmental disorders present with developmental delay. The ultimate diagnosis may take months or even years to be confirmed. The final verdict may be purely developmental with a benign outcome, or there might be slow deterioration ending up in a more sinister cause like neurodegenerative diseases. At times, the developmental course might plateau off with the final developmental outcome underachieved. With standardized assessment at a later age, these children could then be labeled as suffering from "mental retardation' (MR) or "intellectual disability" (ID). Thus, the crucial issue during the process of making the final diagnosis for any child presenting with developmental delay is when can one decide that an etiological diagnosis can confidently be made during the phase of development. When can one be really sure that there is no underlying organic cause to account for the developmental delay. Often than not, the clinician is faced with the dilemma of how exhaustive one should persue in investigating a case of DD, and when to stop investigating further. It is very important for us to develop a logical and practical approach in managing these DD children at the "first" presentation and to establish one's clinical judgment to find the "Best timing" for referral or diagnostic workup. The first step to the approach is the awareness and the differentiation of Partial Developmental Delay (ParDD) from Global Developmental Delay (GDD). We aim to provide the readers an understanding of a practical and evidence based approach for the diagnostic evaluation of a child with DD/MR. We hope this approach can help to improve the diagnostic yield of DD/MR.

The prevalence of asthma in children continues to increase in many parts of the world, with the highest increases in industrialized urban societies. Although the exact cause of the increase remains undefined the "hygiene hypothesis" where lower exposures to infectious agents that stimulate the production of Th1 lymphocytes thus allowing proliferation of Th2 lymphocytes that mediate allergic diseases has gained popularity. Asthma is an inflammatory disorder of the airways mediated by eosinophils and Th2 cytokines. Thus far, efforts at primary prevention have fallen short and therapy is targeted at preventing symptoms, morbidity and mortality and improving the patient's quality of life. International guidelines recommend a stepwise approach to therapy with the inhaled corticosteroids as the most effective therapy for children with all levels of persistent asthma. Patients with intermittent disease (symptoms less than 2 times weekly) can be effectively treated with as needed short-acting β2 agonists. Leukotriene receptor antagonists and cromolyn/nedocromil are alternatives to the inhaled corticosteroids though not as effective. Children inadequately controlled on low daily doses of inhaled corticosteroids can increase the dosage or attempt adjunctive therapy with long-acting inhaled β2 agonists or leukotriene receptor antagonists. In infants and young children less than 5 years of age adjunctive therapy has not been studied. Both inhaled corticosteroids and leukotriene receptor antagonists reduce the risk of exacerbations in wheezing infants. Comparative studies have not been done. Attention has to be paid to delivery systems for aerosolized drugs in children and patient acceptance and compliance requires monitoring. Aerosolized drugs can be effectively delivered by MDI plus valved holding chamber spacer devices with a mask in or nebuliser and mask in young infants.

Systemic lupus erythematosus (SLE) is more severe in children than in adults, and often needs aggressive treatment. Classical (old ) therapies include mostly non-steroid anti-inflammatory drugs, hydroxychloroquine, corticosterois and cyclophosphamide. However, these two latter drugs can induce severe side effects. Recently, new drugs, especially Mycophenolate Mofetyl and anti-CD20 antibody, have been proved to be efficient and well tolerated in adult-onset SLE and may become mainstay therapeutic option for severe chidhood-onset lupus manifestations. Management of complications such as growth failure, osteoporosis, premature atherosclerosis and anti-phospholipid syndrome has also progressed within the last years. Beside these promising perspectives of treatment, psychological support, long-term follow-up and program of transition from the pediatric to the adult care unit remain essential.

Primary vesicoureteric reflux was felt to result from a congenitally short mucosal tunnel length with oblique intravescical insertion but more recent data suggest that primary vesicoureteric reflux is often associated with functional urodynamic abnormalities. There is now sound evidence that primary vesicoureteric reflux has a familial basis; most findings suggest a dominant inheritance with incomplete penetrance. Primary vesicoureteric reflux is often associated with kidney damage, mostly referred to as reflux nephropathy. It has been traditionally assumed that in primary vesicoureteric reflux kidney damage results from reflux of infected urine into the renal tissue but recent observations indicate that kidney damage sometimes occurs prenatally. In the overwhelming majority of patients with prenatally acquired renal damage the damage is linked with high-grade vesicoureteric reflux. In conclusion there are two categories of reflux disorder: a reflux associated with an acquired renal scarring secondary to infections and a prenatal high-grade vesicoureteric reflux linked with a congenital nephropathy.

Paediatric surgeons were among the pioneers of laparoscopic surgery in the early 1970s. However, the vast potential of minimal access surgery in infants and children has only been more fully realised in the past decade. This has been brought about by increasing experience in paediatric laparoscopic procedures, and advances in video technology and miniaturised instruments. Very few complex paediatric surgical conditions are now beyond the scope of minimal access surgery. Benefits of minimal access surgery may include reduced postoperative pain, shortened length of stay, and faster resumption of normal activities. The question now is no longer whether laparoscopic surgery should be done in children, but what conditions should be treated laparoscopically. In this review, we will discuss the scope of laparoscopic surgery in children and focus on recent advance and controversial issues.