Clinical Malnutrition Research Articles

Nutritional risk amongst community-living Maori and non-Maori older people in Hawke’s Bay

Maintaining good nutrition is vital for healthy ageing. Poor nutrition increases the risk of hospitalisation, disability and mortality. Research shows clinical malnutrition is preceded by a state of nutritional risk and screening can identify older people at risk of poor nutrition or who currently have impaired nutritional status. To assess the population prevalence of nutritional risk amongst community-living Maori and non-Maori older people in Hawke's Bay. A postal survey of 1268 people aged 65 years or older on the electoral roll for Hawke's Bay was conducted. Nutritional risk was measured using the SCREEN II questionnaire. Responses from 473 people were received (43.8% male, 49.9% female, 6.3% unspecified) with an estimated average age of 74 years. Nutritional risk was present amongst 56.5% of older people with 23.7% at risk and 32.8% at high risk. Maori were 5.2 times more likely to be at nutritional risk than non-Maori. Older people living alone were 3.5 times more likely to be at nutritional risk than those living with others. The most frequent risk factors were low milk-product intake, perception of own weight being more or less than it should be, and low meat and alternatives intake. Skipping meals and low fruit and vegetable intake were additional frequent risk factors for Maori. Both living situation and ethnicity are associated with nutritional risk. Further investigation is needed to confirm these findings and to determine issues specific for older Maori, including barriers to good nutrition and opportunities for nutritional improvement.

Acute stress-induced thymic atrophy is mediated by intrathymic inflammatory and wound healing responses (113.25)

Abstract Productive thymopoiesis is essential for a robust and healthy immune system. Thymus unfortunately is acutely sensitive to stress resulting in involution and decreased T cell production. Thymic involution is a complication of many clinical settings, including infection, malnutrition, and irradiation or immunosuppressive therapies. Little is known, however, about intrathymic mechanisms that may actively contribute to thymus atrophy or initiate thymic recovery following stress events. In this work, phenotypic, histologic and transcriptome/pathway analysis was performed to identify putative intrathymic mechanisms that drive endotoxemia-induced involution of murine thymic tissue. Thymus atrophy in this murine model was confirmed by down-regulation of genes involved in T cell development, cell activation, and cell cycle progression, correlating with observed phenotypic and histologic thymus involution. Significant gene changes support the hypothesis that multiple key intrathymic pathways are differentially activated during stress-induced thymic involution. These included direct activation of thymus tissue by LPS through TLR signaling, local expression of inflammatory cytokines, inhibition of T cell signaling, and induction of wound healing/tissue remodeling. Taken together, these observations demonstrated that both systemic and direct intrathymic responses to endotoxin challenge concurrently contribute to thymic involution during endotoxemia.

Acute Endotoxin-Induced Thymic Atrophy Is Characterized By Intrathymic Inflammatory and Wound Healing Responses

BackgroundProductive thymopoiesis is essential for a robust and healthy immune system. Thymus unfortunately is acutely sensitive to stress resulting in involution and decreased T cell production. Thymic involution is a complication of many clinical settings, including infection, malnutrition, starvation, and irradiation or immunosuppressive therapies. Systemic rises in glucocorticoids and inflammatory cytokines are known to contribute to thymic atrophy. Little is known, however, about intrathymic mechanisms that may actively contribute to thymus atrophy or initiate thymic recovery following stress events.Methodology/Principal FindingsPhenotypic, histologic and transcriptome/pathway analysis of murine thymic tissue during the early stages of endotoxemia-induced thymic involution was performed to identify putative mechanisms that drive thymic involution during stress. Thymus atrophy in this murine model was confirmed by down-regulation of genes involved in T cell development, cell activation, and cell cycle progression, correlating with observed phenotypic and histologic thymus involution. Significant gene changes support the hypothesis that multiple key intrathymic pathways are differentially activated during stress-induced thymic involution. These included direct activation of thymus tissue by LPS through TLR signaling, local expression of inflammatory cytokines, inhibition of T cell signaling, and induction of wound healing/tissue remodeling.Conclusions/SignificanceTaken together, these observations demonstrated that in addition to the classic systemic response, a direct intrathymic response to endotoxin challenge concurrently contributes to thymic involution during endotoxemia. These findings are a substantial advancement over current understanding of thymus response to stress and may lead to the development of novel therapeutic approaches to ameliorate immune deficiency associated with stress events.

Positive correlations between tumor uptake on FDG PET and energy expenditure of patients with esophageal cancer

Cancer patients are prone to clinical malnutrition; moreover, the energy expenditure in patients with certain cancers is higher than that in healthy individuals, rendering their nutritional management a challenging issue. We hypothesized that 2-deoxy-2-[(18)F]fluoro-D: -glucose (FDG) uptake on positron emission tomography (PET) may be related to the energy expenditure and analyzed the FDG uptake and energy expenditure in esophageal cancer patients to clarify this. Esophageal cancer patients [n = 13, 10 males and 3 females, age 66.5 ± 8.9 (51-82) years] were evaluated for FDG uptake using PET. The resting energy expenditure (REE) and basal energy expenditure (BEE) were calculated using indirect calorimetry and the Harris-Benedict formula, respectively. Regression analyses were performed to compare the parameters of imaging and energy expenditure. Positive correlations were found between tumor uptake on FDG PET and the parameters of energy expenditure. Among them, the correlations between SUV(max) and the ratio of REE to BEE (REE/BEE, r = 0.59; p = 0.035) and between SUV(max) and the difference between REE and BEE (REE - BEE, r = 0.58; p = 0.036) were moderate and statistically significant. Further, the correlation between tumor uptake expressed as a percentage (%TU) and REE/BEE was mild (r = 0.51) but not significant (p = 0.07), while that between %TU and REE-BEE was weak (r = 0.42) and not significant (p = 0.15). Significant positive correlations between SUV(max) on FDG PET and energy expenditure were noted in our study; we consider that these results may aid in determining the nutritional management for esophageal cancer patients.

Conséquences d'une comorbidité trop souvent négligée en cancérologie: la dénutrition

Malnutrition is a common problem in patients with cancer, with a prevalence ranging between 30 and 80%, depending on the criteria used to determine malnutrition and patient characteristics. Malnutrition is a major cause of morbidity and mortality in cancer patients. It is associated with functional impairment, as well as poor outcome and quality of life. The impact on morbidity is persistent, with increased susceptibility to treatment-related adverse events, infection and postoperative complications. Significant weight loss is generally associated with higher mortality, possibly because it makes it impossible to administer the optimal therapeutic program in order to stabilize or cure the disease, in particular because of the patient's poor clinical condition or of increased treatment toxicity. In late stage patients, cachexia can be a direct cause of death. Studies have shown that direct or indirect complications of clinical malnutrition have economic implications; the number and length of hospital stays, as well as treatment and managements costs, are significantly increased in malnourished patients. Since the risk of hospital malnutrition can no longer be ignored, early nutritional assessment at the time of cancer diagnosis is mandatory in order to initiate timely nutritional therapy.

Nutrition Assessment in Long‐Term Care

Assessment of nutrition status is necessary in long-term care settings for both optimal patient care and to meet regulatory standards. Careful nutrition assessment leads to development of an individual plan of care to optimize nutrition status. Although the Minimum Data Set is mandated as the nutrition assessment tool in long-term care settings, published studies show that the use of the Minimum Data Set to assess nutrition status is problematic. Two types of nutrition assessment instruments have been developed. The first type aims to identify those at risk for malnutrition but is not used to diagnose clinical malnutrition, whereas the second type has been designed to diagnose malnutrition. A number of commonly used nutrition assessment tools have not been validated in long-term care populations. This review focuses on the available tools used in the long-term care setting and provides an overview of their characteristics and performance measures.

Clinical malnutrition in severe traumatic brain injury: Factors associated and outcome at 6 months

Traumatic brain injury increases the metabolic response of body, and therefore nutritional demands. This study was undertaken to evaluate various clinical features of malnutrition in TBI and their influence on neurological outcome. Eighty eight adult patients within 24 hours of TBI admitted with GCS 4 to 8 without serious systemic disorder were enrolled for the study. They were monitored serially for various clinical features of malnutrition till 3 weeks and outcome assessed at 6 months. Every week there was a significant increase in number of patients with various clinical features of malnutrition. Pedal edema was the most frequent sign present in 70% of patients at three weeks, followed by skeletal prominence (19%) and cheilosis (12%). Clinical malnutrition showed significant association with poorer GCS (p=0.03), admission hypoproteinemia (p=0.03), and delayed full enteral feeding (p< 0.001). Unfavorable outcome at 6 months was noted in 30 out of 37 patients who had clinical malnutrition as compared to 3 out of 15 patients who had no clinical features of malnutrition (odds ratio 17.2, p< 0.001). In multivariate analysis, clinical malnutrition was significantly associated with unfavorable outcome independent of GCS (p=0.002). Analysis of individual clinical markers revealed pedal edema as the only single clinical marker with significant influence on unfavorable outcome at 6 months (p=0.01). Clinical malnutrition developed more among patients with poorer GCS, admission hypoproteinemia, delayed full enteral feeding, and was associated with unfavorable outcome at 6 months. Among the various clinical markers, only pedal edema showed independent association with unfavorable outcome.

Interactions of malnutrition and immune impairment, with specific reference to immunity against parasites.

KEY POINTS Clinical malnutrition is a heterogenous group of disorders including macronutrient deficiencies leading to body cell mass depletion and micronutrient deficiencies, and these often coexist with infectious and inflammatory processes and environmental problems.There is good evidence that specific micronutrients influence immunity, particularly zinc and vitamin A. Iron may have both beneficial and deleterious effects depending on circumstances.There is surprisingly slender good evidence that immunity to parasites is dependent on macronutrient intake or body composition.

Prognostic Factors of Perforated Sigmoid Diverticulitis in the Elderly

Background: The Finnish population is aging fast and the prevalence of perforated sigmoid diverticulitis is simultaneously increasing in northern Finland. The fact that an increasing number of elderly patients, with their age-specific problems, are subjected to emergency surgery for acute diverticulitis underlines the importance of risk stratification.Methods: One hundred and seventy-two patients admitted to Oulu University Hospital because of diverticular perforation from 1983 to 2002 were identified from the computer database. The clinical variables were evaluated as prognostic indicators of postoperative complications, mortality and time of hospitalization. Results: The resection rate was 91%; 64 primary anastomoses, 93 Hartmann’s procedures and two covering colostomies were performed. The overall complication rate was 33%. In patients under 70 years, a stepwise logistic regression analysis showed that the Mannheim Peritonitis Index (MPI) score and American Society of Anesthesiologists (ASA) score were independent prognostic factors. None of factors predicted morbidity in patients over 70 years. Overall mortality rate was 8%, without any significant difference between the procedures. Of the clinical variables, MPI score, ASA score, Hinchey classes and malnutrition correlated with mortality. All patients who died presented with ASA scores of III–IV, and 12 out of 14 patients had an MPI score of II. In a stepwise logistic regression analysis, only the MPI score seemed to be an independent predictor of mortality. Conclusions: Mortality is related to age but age alone is not an independent predictor of mortality. The MPI score is useful in predicting the risk of death in patients with perforated diverticulitis.

Nutritional and Clinical Status of Children Admitted to the Malnutrition Ward, Maputo Central Hospital: A Comparison of Data from 2001 and 1983

Malnutrition is the fourth commonest reason for hospital admission to the paediatric department of the Central Hospital, Maputo and has the second highest death rate (20 per cent). A study from 1995 into mortality at this paediatric department, suggested an increase in severe malnutrition. Recent studies have shown that the global burden of undernutrition in the world is declining; however, data for Eastern Africa shows a deterioration. The current study was aimed at describing and comparing the patients on the malnutrition ward, in 2001 and 1983. The study gathered indices of nutritional status and secondary diagnoses from the notes of all children (aged between 6 months and 5 years) discharged from the malnutrition ward for a period of l year (January-December 2001), and from data (collected in January-December 1983) for the malnutrition ward. Data was entered and analysed using Epi-Info 6 and SPSS statistics package. The ethics committee of the hospital approved the study. Data was collected for 558 children in 2001 and 833 in 1983. There was no gender difference, average age was 21.7 months in 2001 and 23.8 months in 1983 and the average hospital stay was 13.1 and 14.3 days, respectively. In 2001, 33 per cent had kwashiorkor, 26 per cent marasmus, and 28 per cent marasmic kwashiorkor. Three hundred and twenty children (82 per cent) were <2 Z-scores below the median weight-for-age and 252 children (65 per cent) were <3 Z-scores. Forty per cent had malaria, 65 per cent anaemia, 53 per cent bronchopneumonia, 14 per cent TB, 36 per cent diarrhoea, and 12 per cent HIV/AIDS. In 1983, 49 per cent had kwashiorkor, 17 per cent marasmus, and 11 per cent had marasmic kwashiorkor. A total of 494 children (81 per cent) were <2 Z-scores below the median weight-for-age and 335 children (55 per cent) were <3 Z-scores. Eighteen per cent had malaria, 37 per cent anaemia, 28 per cent bronchopneumonia, 6 per cent TB, 8 per cent diarrhoea, and 4.4 per cent measles/post-measles. A comparison between the clinical status of 1983 with that of 2001 shows little difference in age, gender or length of stay. There were fewer admissions in 2001, although a higher percentage of severely underweight children and the 2001 group had more secondary infections, especially malaria, bronchopneumonia and anaemia. Clinical malnutrition at a referral hospital level, in spite of the remarkable Mozambican economic growth, shows signs of following the depressing pattern for much of Eastern Africa. A prospective study including HIV tests and anthropometric data for this and the city's other hospitals is warranted. Discussion needs to be prompted on a local level about malnutrition and the use of guidelines.

Nutritional screening and assessment in cancer-associated malnutrition

Up to 85% of all patients with cancer develop clinical malnutrition, which negatively affects patients' response to therapy, increases the incidence of treatment-related side effects and can decrease survival. Early identification of patients who are malnourished or at risk of malnutrition can promote recovery and improve prognosis. In addition, early nutritional intervention is cost effective, as it reduces complication rates and length of hospital stay. The development and use of screening and assessment tools is essential for effective nutritional intervention and management of patients with cancer. Nutritional screening aims to identify patients who are malnourished or at significant risk of malnutrition. Patients identified through screening require referral to a dietician or specialist in nutrition for an in-depth nutritional assessment, involving examination of medical, dietary, psychological and social history, physical examination, anthropometry and biochemical testing. Interventions initiated after nutritional assessment should be tailored to the individual and take into consideration the patient's prognosis. Nutritional care is a fundamental aspect of nursing practice and nurses are ideally placed to play an essential role in the early detection and screening of malnutrition in patients with cancer.

Historical Concepts of Interactions, Synergism and Antagonism between Nutrition and Infection

In the 1950s textbooks of nutrition made little or no mention of a relation to infection. The same was true for treatises on infectious disease. Relevant studies in experimental animals and a number of classical clinical observations were available pointing out the role of infection in precipitating nutritional disorders. However, clinicians and nutritionists did not recognize the importance of the relationship. The field and metabolic studies of the Institute of Nutrition of Central America and Panama (INCAP) in the 1950s demonstrated that malnutrition and infection in humans are generally synergistic. These studies stimulated the review of available evidence that resulted in the 1968 WHO monograph on "Interactions of Nutrition and Infection." It provided extensive evidence for the role of infections in precipitating clinical malnutrition and for the impact of malnutrition on morbidity and mortality from infection. The high frequency of diarrhea in underprivileged young children led to intensive studies in many countries of its effect on nutritional status and to recognition of the high prevalence of "weanling diarrhea." The effects of infection on nutritional status were then extensively and elegantly investigated at Fort Detrick, MD, and hormonal and cytokine mechanisms identified. The subsequent explosion in knowledge of cell-mediated immune mechanisms has led to an understanding of how malnutrition lowers this resistance. Today, recognition of the synergistic relationship between nutrition and infection influences most public health interventions to prevent malnutrition.

HIV disease: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

HIV disease: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

Flux of amino acids and energy substrates across the leg in weight-stable HIV-infected patients with acute opportunistic infections: indication of a slow protein wasting process.

Increased whole-body proteolysis with muscle protein net degradation has been suggested as one of the causes of weight loss in patients infected with human immunodeficiency virus (HIV). We studied the exchange rates of amino acids and energy substrates across the lower extremity in 16 HIV patients and 16 age-matched controls with similar body cell mass. The patients had either opportunistic infections or chronic diarrhea but no signs of clinical malnutrition. The following findings were obtained in the HIV patients: an augmented peripheral net release of arginine and lysine; an increase in both the negative arterial-venous difference and the efflux of the nitrogen contained in nonmetabolized amino acids; diminished export of 3-methylhistidine; lowered plasma and erythrocyte amino acid concentrations; reduced output of glycerol and furthermore; and neither a net release nor a net uptake of free fatty acids. The findings concerning nitrogen metabolism support the hypothesis that, in the presence of a reduction in protein breakdown, peripheral protein synthesis is severely depressed, making a slow protein wasting process likely to occur. The balances of glycerol and free fatty acids are due not only to the leg tissues but perhaps also in part to increased net retention of these substrates by skeletal muscle.

Clinical management of early progressive renal failure

In the era of managed health care, the primary physician will be required to play an active role in the management of patients with early renal failure. This section provides a comprehensive and practical approach to the management of such patients. Early recognition of renal failure and monitoring its progression require an understanding of the pitfalls of commonly used diagnostic tests. Tight control of hypertension, angiotensin-converting enzyme inhibition, and dietary protein restriction play important roles in delaying the progression of renal disease. Avoidance of additional renal insults such as nephrotoxic drugs and radiographic contrast prevents acceleration of renal demise. A variety of clinical manifestations, including dyselectrolytemias, hypertension, malnutrition, secondary hyperparathyroidism, and anemia may develop in patients with early renal failure. Timely referral to a nephrologist will facilitate planning for renal replacement therapy and may favorably affect eventual outcomes.

Food consumption in rural and urban Tanzania

Food consumption of 177 rural and 94 urban subjects (98 aged 12 years, 105 aged 35–44 years, and 68 aged 65–74 years) was studied in rural and urban Ilala district, Dar-es-Salaam, Tanzania, to characterize rural–urban differences in the meal and snack patterns and intakes of energy and nutrients. Food consumption of each subject was studied using 24 h dietary recall once during the rainy season and once during the dry season. Micro Nutrica® PC database, expanded with East African food composition tables, was used in the nutrient intake analyses. All urban and 92% of rural subjects had three daily meals, and snacks were as commonly eaten in both areas of the survey. Foods of animal origin, e.g. meat and milk, were seldom used by the rural subjects. The WHO/FAO recommended minimal daily allowances of energy and protein were not reached by 26 and 15% of the rural subjects, respectively (10 and 4% of the urban subjects). Mean intake of folic acid by rural subjects was clearly below that of the urban subjects. Intakes of sucrose, mono- and disaccharides combined, polysaccharides, fibre and cholesterol differed markedly in all age groups in rural and urban circumstances ( P<0.05). Intake of fat and saturated fat was extremely low in all age groups, particularly in the rural subjects. The data suggest that (sub)clinical protein-energy malnutrition is prelevant in Tanzania, and that the high intakes of sucrose and cholesterol and the low intake of fibre by the urban subjects may increase the prevalence of dental caries and cardiovascular diseases in that population.

Sykepleieprotokoll for kostholdsveiledning til pasienter med kreft i mage-tarm kanalen — Et forskningsbasert samarbeide mellom høgskole og sykehus

Cancer in the gatrointestinal tract is a common diagnosis on the two hospitalwards where the study was carried out, and malnutrition is a frequent problem with severe weight-loss. The focus was to improve the nursing support to these patients, as well as aiming for a pedagogical benefit for nursingstudents.The project is based on a model transferring research-based knowledge into an innovation protocol for nursing practice. First phase identified the clinical problem, malnutrition, by nutritionregistration and interviewes of 18 patients about their knowledge of nutrition. Second phase described the innovation and dealt with the planning and implementing of students' nutritionguide to 15 patients. Third phase implied the evaluation of the effects of the nutritionguide, and outlining of the protocol. The results confirm severe malnutrition, as well as the need for nutritional support. The patients benefitted only to a certain degree from the students' nutritionguidance. However, the protocol has resulted in...

RESPONSE OF THE INTESTINAL EPITHELIUM TO METHOTREXATE INDUCED DAMAGE

One of the major side effects of chemotherapy is severe damage to the intestinal epithelium, leading to impairment of the intestinal function. Especially in pediatric patients, clinical symptoms like malabsorption, malnutrition and anorexia are of great concern. Aim: To gain insight in the regulation of epithelial proliferation, differentiation and cell death during damage and regeneration in order to develop prophylactic/therapeutic regimes to avoid or repair intestinal damage. Methods: Since morphological alterations after chemotherapy are similar in rat and human small intestine, we focussed on rats treated with methotrexate (MTX). Duodenal and jejunal segments were excised on various days after a single i.v. dose of MTX. Next to standard histological evaluation, differentiation of the epithelial cells was assessed by the expression of cell-type specific differentiation markers at mRNA (in situ hybridization) and protein (immunohistochemistry) levels. Sucrase-isomaltase (SI) and intestinal fatty acid binding protein (iFABP) were used as differentiation markers for enterocytes, mucin (MUC2) for goblet cells, and lysozyme for Paneth cells. In addition, proliferating and apoptotic epithelial cells were assessed by immunodetection of proliferating cell nuclear antigen (PCNA) and the terminal uridine deoxynucleotide nick-end labeling (TUNEL) method, respectively. Results: Morphologically, intestinal damage at 2 days after MTX injection is characterized by disturbance of the crypt architecture and shortening of the villi. On day 4 the villus atrophy is even more pronounced, while the crypts are elongated. Both, the crypt- and villus architecture has been restored completely on day 6. Expression of the enterocyte specific differentiation markers showed a decrease of SI while iFABP remained stable at both mRNA- and protein levels. Moreover, expression of the Paneth cell marker lysozyme (on day 2-4) and the goblet cell marker MUC2 (on day 4) are increased at both levels investigated. There is an increase in TUNEL positive cells in the crypts on day 2, which is followed by an increase in PCNA-positive cells on day 4. Conclusions: During MTX-induced damage, lysozyme and MUC2 expression are increased, which implies an increased production of protective molecules. The MTX-induced decrease in SI expression and the unaltered iFABP expression suggest a differential effect on expression of these genes in enterocytes. This might indicate a switch in enterocyte metabolism from sugar absorption to fatty acid absorption. Since alterations in mRNA and corresponding protein levels correlate well for each differentiation marker, the effects of MTX occur mainly at the mRNA level. Furthermore, single dose MTX treatment leads to increased apoptosis in crypts followed by an increase of proliferative activity in crypts as demonstrated by the histological changes, TUNEL method and PCNA expression patterns.

The new paradigm of public health nutrition.

Poor food habits that result in nutritional deficiencies and excesses along with smoking infections and toxic environmental factors are the major determinants of the health and longevity of individuals. Fetal malnutrition reflects the nutritional status and health of the mother. Iodine deficiency marasmus kwashiorkor and lesser degrees of protein-energy deficiency can also have lasting functional consequences. Stunting associated with clinical malnutrition also exerts a lasting effect on learning and behavior. Nutritional supplementation of young children beneficially affects cognitive development and performance. Two well-designed studies in the late 1960s in Guatemala and Mexico demonstrated that supplementary feeding up to 2 years of age benefited rural breast-fed children who were taller had fewer infections and performed better on cognitive tests. In Guatemala over 2000 of these children performed better on comprehensive achievement tests and had completed more years of schooling when reexamined as adolescents and young adults. In a study of infants born between 1935 and 1943 blood pressure of adult men and women was strongly predicted by high placental weight combined with birth weight. Increased insulin tolerance and adult onset diabetes are also more common among individuals 45 to 54 years old with low weight at birth and at 1 year of age. Iron deficiency anemia in developing countries amounts to 26% for men and nearly 50% for women and children. The adverse consequences of anemia include weakness decreased physical capacity and impaired cognitive performance and growth of children. Osteoporosis is strongly influenced by diets low in calcium at an early age. Cancers are greatly influenced by environmental factors including diet. The 1989 US National Research Council Report on diet and health estimated the 35% to 40% of cancers in the United States were diet related. In summary fulfillment of the genetic potential of individuals is impaired by malnutrition and other environmental factors throughout life.

Failure of monocyte priming in clinical protein malnutrition: [formula omitted], C.W. Ramsden, P.J. Guillou and J.V. Reynolds. Academic Surgical Unit, St. Jame's University Hospital, Leeds LS9 7TF U.K.

Failure of monocyte priming in clinical protein malnutrition: [formula omitted], C.W. Ramsden, P.J. Guillou and J.V. Reynolds. Academic Surgical Unit, St. Jame's University Hospital, Leeds LS9 7TF U.K.