Managing infants, children and adolescents, ranging from premature infants to 18-year-old adolescents, on parenteral nutrition (PN) is a challenge. The ability of children to withstand starvation is limited and, unlike adults, children require nutrition for growth. PN in children is often required secondary to a congenital bowel problem rather than because of an acquired condition. Conditions requiring PN include motility disorders, congenital disorders of the intestinal epithelium and short-bowel syndrome (SBS). Intestinal failure may be temporary and children with SBS may be weaned from PN. However, other children require permanent PN. There are no comprehensive guidelines for the nutritional requirements of children and adolescents requiring PN. Practice in individual centres is based on clinical experience rather than clinical trials. Requirements are assessed on an individual basis according to age, nutritional status and clinical condition. These requirements need regular review to ensure that they remain appropriate for the changing age and weight of the child. Assessments of intakes use different methods, e.g. reference tables and predictive equations. Complications of PN include infection, accidental damage to, or removal of, the line and cholestatic liver disease. Home parenteral nutrition (HPN) is associated with fewer line infections and allows continuation of nutritional support in a more normal environment, encouraging normal development and participation in family activities. However, having a child at home on HPN is associated with physical and psychological stresses. A feeling of depression, loneliness and social isolation is common amongst children and their families. Home-care services are essential to supporting children at home and should be tailored to, and sensitive to, the individual needs of each family.

The paper discusses the case histories of three patients who have faced the emotional implications of being initiated onto long-term parenteral nutrition (PN). In each case the patient's personal and family history, relationship to their illness and the presence or relative absence of resentments and grievances have influenced their ability to tolerate the training and the transition to home PN (HPN). In addition, the emotional importance of food and feeding from a developmental and social perspective is explored, together with the numerous psychological and social ‘losses’ experienced by all patients on PN and the adaptations required within the family setting. The ‘meaning’ of PN to the individual and the need for both internal and external support are identified and, based on clinical experience, a number of features are described that may be indicative of the relative abilities of different patients to cope with HPN. Finally, the role of a dedicated Psychological Medicine Unit closely allied to a nutrition service is discussed.

Pathophysiological stress from acute illness causes metabolic disturbance, including altered hepatic glucose metabolism, increased peripheral insulin resistance and hyperglycaemia. Acute hyperglycaemia is associated with increased morbidity and mortality in patients in intensive care units and patients with acute respiratory disease. The present review will consider mechanisms underlying this association. In normal lungs the glucose concentration of airway secretions is approximately 10-fold lower than that of plasma. Low airway glucose concentrations are maintained against a concentration gradient by active glucose transport. Airway glucose concentrations become elevated if normal homeostasis is disrupted by a rise in blood glucose concentrations or inflammation of the airway epithelium. Elevated airway glucose concentrations are associated with and precede increased isolation of respiratory pathogens, particularly methicillin-resistant Staphylococcus aureus, from bronchial aspirates of patients intubated on intensive care. Markers of elevated airway glucose are associated with similar patterns of respiratory infection in patients admitted with acute exacerbations of chronic obstructive pulmonary disease. Glucose at airway concentrations stimulates the growth of respiratory pathogens, over and above the effect of other nutrients. Elevated airway glucose concentrations may also worsen respiratory disease by promoting local inflammation. Hyperglycaemia may thus promote pulmonary infection, at least in part, by an effect on airway glucose concentrations. Therapeutic options, including systemic control of blood glucose and local manipulation of airway glucose homeostasis, will be considered.

Glutamine, the most abundant amino acid in the body, is thought to become conditionally essential in critical illness. Some of the important roles for glutamine are as a carrier for inter-organ N, a preferred fuel for enterocytes and cells of the immune system, a substrate for renal NH3 formation and a precursor for glutathione. Mechanisms by which glutamine could improve recovery include attenuating oxidant damage and inflammatory cytokine production, reducing gut bacterial translocation and improving N balance. The present systematic review has found trends to suggest that parenteral and enteral glutamine supplementation reduce mortality, the development of infection and organ failure in critical illness. Trials of parenteral nutrition containing glutamine with patients after elective surgery also suggest reduction of infection, but it is unlikely that glutamine-containing parenteral nutrition would be used for such patients. The evidence base is limited by the quality of the reported trials and the suggestion that there is publication bias, with trials suggesting reduced infection being more likely to be published.

During critical illness free radical production may increase as a result of, for example, sepsis or tissue trauma. In addition, because of a potential for increased losses, and the possibility of inadequate nutrition, the antioxidant defences of the body may become compromised. Thus, the delicate balance between free radicals and antioxidants may be disturbed. Various nutritional and pharmacological strategies to enhance antioxidant defences have been proposed, which aim either to maintain or enhance endogenous antioxidant stores or to provide alternative antioxidant agents. Trace elements and amino acids are particularly important, and their synergistic role in the maintenance of the body's antioxidant defence network will be discussed.

Critically-ill patients experience an extent of hyperinflammation, cellular immune dysfunction, oxidative stress and mitochondrial dysfunction. Supplementation with key nutrients, such as glutamine and antioxidants, is most likely to have a favourable effect on these physiological derangements, leading to an improvement in clinical outcomes. The results of two meta-analyses suggest that glutamine and antioxidants may be associated with improved survival. The purpose of the present paper is to report the background rationale and study protocol for the evaluation of the effect of high-dose glutamine and antioxidant supplementation on mortality in a large-scale randomized trial in 1200 mechanically-ventilated, critically-ill patients. Patients admitted to an intensive care unit (ICU) with clinical evidence of severe organ dysfunction will be randomized to one of four treatments in a 2×2 factorial design: (1) glutamine; (2) antioxidant therapy; (3) glutamine and antioxidant therapy; (4) placebo. The primary outcome for this study is 28 d mortality. The secondary outcomes are duration of stay in ICU, adjudicated diagnosis of infection, multiple organ dysfunction, duration of mechanical ventilation, length of stay in hospital and health-related quality of life at 3 and 6 months. A novel design feature is the combined use of parenteral and enteral study nutrients dissociated from the nutrition support. The therapeutic strategies tested in the randomized trial may lead to less morbidity and improved survival in critically-ill patients. The trial will be conducted in approximately twenty tertiary-care ICU in Canada and the first results are expected in 2009.

Excessive or inappropriate inflammation and immunosuppression are components of the response to surgery, trauma, injury and infection in some individuals and can lead, progressively, to sepsis and septic shock. The hyperinflammation is characterised by the production of inflammatory cytokines, arachidonic acid-derived eicosanoids and other inflammatory mediators, while the immunosuppression is characterised by impairment of antigen presentation and of T-helper lymphocyte type-1 responses. Long-chain n-3 fatty acids from fish oil decrease the production of inflammatory cytokines and eicosanoids. They act both directly (by replacing arachidonic acid as an eicosanoid substrate and by inhibiting arachidonic acid metabolism) and indirectly (by altering the expression of inflammatory genes through effects on transcription factor activation). Thus, long-chain n-3 fatty acids are potentially useful anti-inflammatory agents and may be of benefit in patients at risk of hyperinflammation and sepsis. As a consequence, an emerging application for n-3 fatty acids, in which they may be added to parenteral (or enteral) formulas, is in surgical or critically-ill patients. Parenteral nutrition that includes n-3 fatty acids appears to preserve immune function better than standard formulas and appears to diminish the extent of the inflammatory response. Studies to date are suggestive of clinical benefits from these approaches, especially in patients post surgery, although evidence of clinical benefit in patients with sepsis is emerging.

The involvement of free radical mechanisms in the pathogenesis of alcoholic liver disease (ALD) is demonstrated by the detection of lipid peroxidation markers in the liver and the serum of patients with alcoholism, as well as by experiments in alcohol-feed rodents that show a relationship between alcohol-induced oxidative stress and the development of liver pathology. Ethanol-induced oxidative stress is the result of the combined impairment of antioxidant defences and the production of reactive oxygen species by the mitochondrial electron transport chain, the alcohol-inducible cytochrome P450 (CYP) 2E1 and activated phagocytes. Furthermore, hydroxyethyl free radicals (HER) are also generated during ethanol metabolism by CYP2E1. The mechanisms by which oxidative stress contributes to alcohol toxicity are still not completely understood. The available evidence indicates that, by favouring mitochondrial permeability transition, oxidative stress promotes hepatocyte necrosis and/or apoptosis and is implicated in the alcohol-induced sensitization of hepatocytes to the pro-apoptotic action of TNF-α. Moreover, oxidative mechanisms can contribute to liver fibrosis, by triggering the release of pro-fibrotic cytokines and collagen gene expression in hepatic stellate cells. Finally, the reactions of HER and lipid peroxidation products with hepatic proteins stimulate both humoral and cellular immune reactions and favour the breaking of self-tolerance during ALD. Thus, immune responses might represent the mechanism by which alcohol-induced oxidative stress contributes to the perpetuation of chronic hepatic inflammation. Together these observations provide a rationale for the possible clinical application of antioxidants in the therapy for ALD.

Mounting epidemiological evidence indicates an association between the moderate ingestion of alcoholic beverages and higher bone mineral density (v. abstainers). More limited findings provide some evidence for translation of this association into reduced fracture risk, but further studies are required. Here, these data are reviewed and caveats in their assimilation, comparison and interpretation as well as in the use and application of bone health indices are discussed. Whilst it is concluded that evidence is now strong for the moderate alcohol–bone health association, at least in relation to bone mineral density, mechanisms are less clear. Both ethanol and non-ethanol components have been implicated as factors that positively affect bone health in the light of moderate consumption of alcoholic beverages, and four particular areas are discussed. First, recent findings suggest that moderate ethanol consumption acutely inhibits bone resorption, in a non-parathyroid hormone- and non-calcitonin-dependent fashion, which can only partly be attributed to an energy effect. Second, critical review of the literature does not support a role for moderate ethanol consumption affecting oestrogen status and leading to a knock-on effect on bone. Third, Si is present at high levels in certain alcoholic beverages, especially beer, and may have a measurable role in promoting bone formation. Fourth, a large body of work indicates that phytochemicals (e.g. polyphenols) from alcoholic beverages could influence bone health, but human data are lacking. With further work it is hoped to be able to model epidemiological observations and provide a clear pathway between the magnitude of association and the relative contribution of these mechanisms for the major classes of alcoholic beverage.

In rural Gambia the risk of mainly infection-related mortality is 10-fold higher for adults born in the nutritionally-debilitating ‘hungry’ season, suggesting that immune function may be compromised by events early in life. The current programme of research focuses on the biological mechanisms underlying this hypothesis, exploring early-life environmental influences on immune development and the long-term functional consequences these influences may have. Results obtained to date show that thymus development during infancy is critically sensitive to environmental exposures, with smaller thymuses observed in the hungry season. Measurement of the frequency of T-cell receptor excision circles indicate that thymus function is also sensitive to seasonal influences, with further studies implicating variations in breast-milk IL-7 as a possible mediator of these effects. Studies in adults have shown that size at birth is positively correlated with antibody responses to vaccination with polysaccharide antigens, thus providing evidence for long-term functional deficits. The present paper will review progress made to date within this field of research.

Undernutrition profoundly affects immune responses, particularly at the extremities of life: in infants and in the elderly. The present review focuses on this interrelationship in the elderly. It describes three different stages of ageing: stage 1, healthy ageing, which is observed in very healthy elderly individuals who have no nutritional deficit; stage 2, common ageing, which is observed in most elderly individuals in whom various micronutrient deficits are found; stage 3, pathological ageing, which is observed in patients with protein–energy deficiency. Stage 1, primary immune ageing, is essentially characterized by changes in T-cell subsets but no change in T-cell function; T-cell function is reduced only in the very elderly (>90 years old). Stage 2, secondary immune ageing, is influenced by micronutrient deficits that may be corrected by providing nutritional supplements. Furthermore, immune responses may also be enhanced by supplementation of subjects who have no micronutrient deficits, indicating that the immune system of elderly individuals is highly susceptible to the influence of micronutrients. In stage 3, tertiary immune ageing, the immune responses are strongly related to the decreased nutritional status. In these patients decreased immune responses lead to long-lasting acute-phase responses, which induce greater use of nutritional reserves during disease and lead to increased frailty. As nutritional status has a marked effect on immune responses in elderly individuals, nutritional therapy should be given to elderly individuals who have nutrient deficits, and perhaps also to individuals who do not have nutrient deficits in order to promote healthy ageing and extend the lifespan.