The epidemic of ‘obesity’ in India is not appreciated because BMI underestimates the adiposity of Indians. Specific adiposity measurements are necessary for recognition of the adiposity of ‘thin’ Indians. The origin of this adiposity is only beginning to be understood. In addition to a possible genetic predisposition, intrauterine ‘programming’ might be responsible, although in the ‘thrifty phenotype’ hypothesis the adiposity of the ‘thin’ fetus has not been appreciated. Dutch men who faced ‘winter hunger’ during the first trimester of their in utero life have become more obese as adults. Low birth weight predicts central obesity in some studies, including studies in urban children. It has also been shown that small and thin Indian newborns (weight 2·7?kg and ponderal index 2·4?kg\m3) have poor muscle and visceral mass but higher adiposity for a given weight compared with white Caucasian babies. This body composition is influenced by maternal adiposity before pregnancy and by aspects of maternal nutritional intake and circulating nutrient concentrations during pregnancy. There are no strong paternal determinants of adiposity at birth. Adiposity may be an integral part of the orchestrated adjustments made to support ‘brain preservation’ during intrauterine growth, because brain tissue is predominantly fat. Increased nutrition in the face of a genetic predisposition or multigenerational undernutrition increases maternal insulin resistance in late pregnancy and promotes fetal adiposity even in absence of marked hyperglycaemia. Further research is necessary to define the role of specific nutrients and metabolites in the intrauterine processes promoting adiposity before maternal interventions to curtail the epidemic of obesity and diabetes are planned.

It is apparent from epidemiological studies that the timing of maternal nutrient restriction has a major influence on outcome in terms of predisposing the resulting offspring to adult obesity. The present review will consider the extent to which maternal age, parity and nutritional restriction at defined stages of gestation can have important effects on fat deposition and endocrine sensitivity of adipose tissue in the offspring. For example, in 1-year-old sheep the offspring of juvenile mothers have substantially reduced fat deposition compared with those born to adult mothers. Offspring of primiparous adult mothers, however, show increased adiposity compared with those born to multiparous mothers. These offspring of multiparous ewes show retained abundance of the brown adipose tissue-specific uncoupling protein 1 at 1 month of age. A stimulated rate of metabolism in brown fat of these offspring may act to reduce adipose tissue deposition in later life. In terms of defined windows of development that can programme adipose tissue growth, maternal nutrient restriction targetted over the period of maximal placental growth results in increased adiposity at term in conjunction with enhanced abundance of mRNA for the insulin-like growth factor-I and -II receptors. In contrast, nutrient restriction in late gestation, coincident with the period of maximal fetal growth, has no major effect on adiposity but results in greater abundance of specific mitochondrial proteins, i.e. voltage-dependent anion channel and/or uncoupling protein 2. These adaptations may increase the predisposal of these offspring to adult obesity. Increasing maternal nutrition in late gestation, however, can result in proportionately less fetal adipose tissue deposition in conjunction with enhanced abundance of uncoupling protein 1.

Exposure to either an increased or decreased level of intrauterine nutrition can result in an increase in adiposity and in circulating leptin concentrations in later life. In animals such as the sheep and pig in which fat is deposited before birth, leptin is synthesised in fetal adipose tissue and is present in the fetal circulation throughout late gestation. In the sheep a moderate increase or decrease in the level of maternal nutrition does not alter fetal plasma leptin concentrations, but there is evidence that chronic fetal hyperglycaemia and hyperinsulinaemia increase fetal fat mass and leptin synthesis within fetal fat depots. Importantly, there is a positive relationship between the relative mass of the ‘unilocular’ component of fetal perirenal and interscapular adipose tissue and circulating fetal leptin concentrations in the sheep. Thus, as in the neonate and adult, circulating leptin concentrations may be a signal of fat mass in fetal life. There is also evidence that leptin can act to regulate the lipid storage, leptin synthetic capacity and potential thermogenic functions of fat before birth. Thus, leptin may act as a signal of energy supply and have a ‘lipostatic’ role before birth. Future studies are clearly required to determine whether the intrauterine and early postnatal nutrient environment programme the endocrine feedback loop between adipose tissue and the central and peripheral neuroendocrine systems that regulate energy balance, resulting in an enhanced risk of obesity in adult life.

High circulating concentrations of leptin in obesity are associated with an apparent loss of its characteristic anorexic action within the hypothalamic region of the brain. Central insensitivity to leptin may therefore contribute to the aetiology of this disease, and an increased understanding of the underlying mechanisms will identify potential means of prevention and/or therapeutic targets. Seasonal animals such as sheep and Siberian hamsters (Phodopus sungorus) exhibit annual photoperiod-driven cycles of appetite and body weight. Increased food intake and weight gain in long days (summer) are associated with high circulating leptin, and decreased intake and weight loss in short days (winter) with low leptin. Critically, these cycles are associated with reversible changes in sensitivity to leptin. High sensitivity is seen in short days and relative insensitivity in long days, demonstrated both in sheep given leptin centrally via intracerebroventricular cannulas and in hamsters given leptin peripherally. In addition, primary hypothalamic appetite-regulating targets for leptin (i.e. neuropeptide Y, melanocortin and cocaine- and amphetamine-regulated transcript pathways) respond differently in these species to changes in circulating leptin and nutritional status induced by photoperiod as opposed to such changes induced by food restriction. Studies of seasonal animals will help to resolve causes of altered sensitivity to leptin and whether these changes reflect altered transport into the brain and/or altered signalling at the receptor or post-receptor level. Increased knowledge of the mechanism(s) and time-course for development and reversal of reduced central leptin sensitivity will provide new insights into the development and control of obesity.

The introduction of the process of nutritional screening into clinical standards has been driven by the increasing awareness of the prevalence of undernutrition in acute and primary care, along with its associated morbidity and mortality. However, the increasing prevalence of obesity in the general population suggests that an increased number of patients admitted to hospital will be obese. Increased morbidity has also been reported in the injured obese patient and may be associated with poor nutritional support. This situation may occur because the profound metabolic disturbances accompanying trauma in this group are not recognised, and subsequent feeding practices are inappropriate. Screening tools currently classify patients by using simple markers of assessment at the whole-body level, such as BMI. Subsequently, patients are identified as at risk only if they are undernourished. Such comparisons would by definition classify injured obese patients as at minimal or no nutritional risk, and they would therefore be less likely to be re-screened. This approach could result in potential increases in morbidity, length of rehabilitation and consequent length of hospital stay. It is likely that the identification of potential risk in obese injured patients goes beyond the measurement of such indices as BMI and percentage weight loss, which are currently utilised by the majority of screening processes.

The World Health Organization's (1990) definition of palliative care describes an holistic approach to care for patients with advanced progressive illness. Issues relating to nutrition, lack of appetite and the subsequent weight loss the individuals may experience present a challenge to all concerned with providing both formal and informal care to this patient group. The philosophy of palliative care requires a multidisciplinary approach to the constellation of issues and problems related to food that are faced by both patients and carers in receipt of palliative care. The literature in this area is mainly related to those patients with a cancer diagnosis. The developing role of palliative care in patients with non-malignant disease provides further challenges for health care professionals. The present paper aims to reflect an entire philosophical approach to care through an examination of one area of practice.

Data from the European Society for Parenteral and Enteral Nutrition Home Artificial Nutrition Survey suggest that the use of home parenteral nutrition (HPN) in patients with cancer as the primary diagnosis varies markedly between different countries in Europe, being highest in The Netherlands and low in the UK. This finding is difficult to explain on the basis of cancer incidence. The main indication for HPN remains malignant gastrointestinal tract obstruction, which occurs most frequently in gynaecological and colon cancers. The use of HPN should be planned in the light of the proposed cancer treatment and should be discussed beforehand with the patient. Before HPN is considered, a patient should typically require intravenous fluids to maintain hydration, be capable of self care, be able to control the treatment, have an expected survival of ≥3 months and have no other available route of feeding. The effect of HPN on quality of life remains controversial, but nutrition is only one of the factors that influence the quality of life in cancer patients. The differing rates of HPN in Europe are probably related to cultural attitudes to incurable cancer as much as to meeting the nutritional needs of the patient.

The medical care of patients with sepsis or severe inflammatory response syndromes has seen tremendous technological advancements in recent years; yet, several clinical studies with anti-cytokine therapies targetted to this population have met with disappointing results. Four primary factors have been identified that represent potential pitfalls involving the use of biological response modifiers in critically-ill patients. First, the physiological response in the stressed patient is complex. Redundancy within this system may not allow a single intervention to produce a clinical response. Second, the critically-ill patient population is heterogenous and important factors including the age of the patient, associated co-morbidities, the nature of the original injury and the presence or absence of an ongoing injury can modulate the effectiveness of a specific therapy. Third, the timing of the therapeutic intervention can be difficult to standardize among patients and can often produce differing results. A greater understanding of the physiological response to injury has shown that there are both proinflammatory and anti-inflammatory processes ongoing simultaneously. Determining the optimal time to intervene within this framework can be problematic. Fourth, the presence of genetic polymorphisms within the general population has identified subsets of individuals who may have different physiological responses to similar stresses. The relative proportions of patients with these polymorphisms within clinical trials may affect outcome and data analysis. Thus, a better understanding of these issues will result in improvement of the experimental design of clinical trials involving anti-cytokine therapies and critically-ill patients. Avoidance of these pitfalls will enhance the quality and utility of outcomes research in this subset of patients.

The ongoing hypermetabolic response in patients with prolonged critical illness leads to the loss of lean tissue mass. Since the cachexia of prolonged illness is usually associated with low concentrations of anabolic hormones, hormonal intervention has been thought to be beneficial. However, most interventions have been shown to be ineffective and their indiscriminate use even causes harm. Before considering endocrine intervention in these frail patients, a detailed understanding of the neuroendocrinology of the stress response is warranted. It is now clear that the acute phase and the later phase of critical illness behave differently from an endocrinological point of view. The acute stress reponse consists primarily of an actively-secreting pituitary in the presence of low circulating peripheral anabolic hormones, suggesting resistance of the peripheral tissues to the effects of anterior pituitary hormones. However, when the disease process becomes prolonged, there is a uniformly-reduced pulsatile secretion of anterior pituitary hormones with proportionally reduced concentrations of peripheral anabolic hormones. The origin of this suppressed pituitary secretion is located in the hypothalamus, as hypothalamic secretagogues can reactivate the anterior pituitary and restore pulsatile secretion. The reactivated pituitary secretion is accompanied by an increase in peripheral target hormones, indicating at least partial sensitivity of these tissues to anterior pituitary hormones in this chronic phase of illness. Thus, endocrine intervention with a combination of hypothalamic secretagogues that more completely reactivate the anterior pituitary could be a more physiological and effective strategy for inducing anabolism in patients with prolonged critical illness.

There is ongoing debate about the respective roles of enteral and parenteral nutrition. The present short review suggests that these two feeding modalities are not mutually exclusive and that optimal nutritional support may necessitate the concomitant administration of enteral together with parenteral nutrition.

Fluid and electrolyte balance is often poorly understood and inappropriate prescribing can cause increased post-operative morbidity and mortality. The efficiency of the physiological response to a salt or water deficit, developed through evolution, contrasts with the relatively inefficient mechanism for dealing with salt excess. Saline has a Na+:Cl-of 1:1 and can produce hyperchloraemic acidosis, renal vasoconstriction and reduced glomerular filtration rate. In contrast, the more physiological Hartmann's solution with a Na+:Cl-of 1·18:1 does not cause hyperchloraemia and Na excretion following infusion is more rapid. Salt and water overload causes not only peripheral and pulmonary oedema, but may also produce splanchnic oedema, resulting in ileus or acute intestinal failure. This overload may sometimes be an inevitable consequence of resuscitation, yet it may take 3 weeks to excrete this excess. It is important to avoid unnecessary additional overload by not prescribing excessive maintenance fluids after the need for resuscitation has passed. Most patients require 2–2·5 litres water and 60–100?mmol?Na\d for maintenance in order to prevent a positive fluid balance. This requirement must not be confused with those for resuscitation of the hypovolaemic patient in whom the main aim of fluid therapy is repletion of the intravascular volume. Fluid and electrolyte balance is a vital component of the metabolic care of surgical and critically-ill patients, with important consequences for gastrointestinal function and hence nutrition. It is also of importance when prescribing artificial nutrition and should be given the same careful consideration as other nutritional and pharmacological needs.

Malnutrition remains a problem in surgical and critically-ill patients. In surgical patients the incidence of malnutrition ranges from 9 to 44%. Despite this variability there is a consensus that malnutrition worsens during hospital stay. In the intensive care unit (ICU), 43% of the patients are malnourished. Although poor nutrition during hospitalisation may be attributable to many factors, not least inadequacies in hospital catering services, there must also be the question of whether those patients who receive nutritional support are being fed appropriately. Indirect calorimetry is the ‘gold standard’ for determining an individual's energy requirements, but limited time and financial resources preclude the use of this method in everyday clinical practice. Studies in surgical and ICU patient populations have been reviewed to determine the ‘optimal’ energy and protein requirements of these patients. There are only a small number of studies that have attempted to measure energy requirements in the various surgical patient groups. Uncomplicated surgery has been associated with energy requirements of 1·0–1·15×BMR whilst complicated surgery requires 1·25–1·4×BMR in order to meet the patient's needs. Identifying the optimal requirements of ICU patients is far more difficult because of the heterogeneous nature of this population. In general, 5·6 kJ (25 kcal)/kg per d is an acceptable and achievable target intake, but patients with sepsis or trauma may require almost twice as much energy during the acute phase of their illness. The implications of failing to meet and exceeding the requirements of critically-ill patients are also reviewed.

At the outset of the research programme into irritable bowel syndrome (IBS) it was perceived that there was a need to develop a symptom-based classification for the patients. Four groups of patients were identified, those with spastic colon syndrome, diarrhoea-predominant spastic colon syndrome, functional diarrhoea and midgut dysmotility. While working with outpatients with IBS it was noted how some of them had suffered symptoms for many years; specifically, a group of patients satisfying the criteria for midgut dysmotility had also suffered from particularly severe and intractable intestinal symptoms. These patients underwent 24 h ambulatory studies of small intestinal motility and the majority were found to have manometric features of chronic idiopathic intestinal pseudo-obstruction (CIIP). To characterise the cause, laparoscopic full-thickness small intestine and colonic biopsies have been obtained in forty-five of the latter group of patients. Of these patients 58% have been found to have complete or partial deficiency of α-actin epitope staining in the inner circular layer of small intestinal smooth muscle. This deficiency is believed to represent an important biomarker rather than the cause of CIIP, since α-actin epitope deficiency has been observed in association with enteric neuropathy and myopathies. In relation to the management of CIIP patients, a multidisciplinary model is proposed incorporating management of co-morbid psychological and psychiatric pathology, abdominal and musculoskeletal pain, fatigue, urological symptoms and nutrition. A six-stage nutritional management plan for these patients is presented.

As the 21st century moves forward, it is becoming more and more apparent that the genetic makeup of any individual strongly influences the way they metabolise nutrients. It is very important, therefore, to understand the techniques and technologies used to assess the contribution genes make to the physiology of an individual. Clearly, it is not possible to provide a comprehensive overview, but in the present review an attempt will be made to show, using examples from the authors' research, how these methods have contributed to this understanding. Studies are being undertaken into Fe transport across the placenta, from the mother to the fetus, and the consequences of maternal anaemia on pregnancy outcome. Levels of gene transcript and protein have been measured using Northern and Western blotting respectively. During the course of this work a new protein has been identified using the available human genome database. Following this ‘in silico’ or ‘cyber biology’, techniques such as real-time RT–PCR and RNA interference have been used to examine expression of this gene and its protein. The methods used, briefly how they work and some of their limitations will be explained. The objective of the present review is primarily to give a better perception of how molecular biology can be used in research and to help gain a clearer understanding of some of the techniques used.

There is extensive evidence to show that there is considerable variation in diet and disease patterns in Europe and that many of the dietary patterns are predictive of chronic disease. Increasingly, there is evidence that this dietary effect is mediated by genetic background. The present paper examines the role of polymorphisms within three genes, those responsible for the synthesis of apoE, 5,10-methylenetetrahydrofolate reductase (MTHFR) and PPARγ. There is clear evidence to support the concept that the diet–disease link is moderated by genetic variation. The paper then considers whether this moderating effect will have implications for dietary recommendations. In the formulation of dietary reference values it has long been recognized that these values cannot cover the needs of all individuals. By setting the upper level at the mean value +2 sd, the needs of 97·5% of the population are covered. Setting a hypothetical scenario of a nutrient requirement of 200 mg\d and a polymorphism with an allelic frequency in the general population in the range of 0, 10, 20 and 30% that causes an increased nutrient requirement of 25%, there was no evidence that the traditional approach requires revision. Whilst it is recognized that genetic variability may not influence population goals, genetic variability will have to be taken into account in the clinical nutrition management of disease. To knowingly assign a patient to life-long treatment with a diet that for genetic reasons will have no success is both unethical and uneconomical. Once accepted in clinical nutrition, the diet–gene interaction will filter into the prevention of disease in public health nutrition.