Abstract: BACKGROUND & AIMS: Though a great interest and willingness to nutrition therapy, there is an insufficient practice compared to the proposed ESPEN guidelines for nutrition therapy. The aim of this questionnaire was to study doctors and nurses' self-reported knowledge in nutritional practice, with focus on ESPEN's guidelines in nutritional screening, assessment and treatment. METHODS: A questionnaire about different aspects of nutritional practice was answered by 4512 doctors and nurses in Denmark, Sweden and Norway. RESULTS: The most common cause for insufficient nutritional practice was lack of nutritional knowledge. Twenty-five percent found it difficult to identify patient in need of nutritional therapy, 39% lacked techniques for identifying malnourished patients, and 53% found it difficult to calculate the patients' energy requirement and 66% lacked national guidelines for clinical nutrition. Twenty-eight percent answered that insufficient nutrition practice could lead to complications and prolonged hospital stay. Those that answered that their nutritional knowledge was good had also a better nutritional practice. CONCLUSION: The self-reported nutritional knowledge was inadequate among Scandinavian doctors and nurses. Increased nutritional knowledge seems to improve the nutritional practice. A combination of an integrated nutrition curriculum during the education, together with post-graduated education for both physicians and nurses should be established.

Abstract: BACKGROUND & AIMS: The aim of the study was to implement nutritional risk screening (NRS-2002) and to assess the association between nutritional risk and clinical outcome. METHODS: NRS-2002 was implemented in 26 hospital departments (surgery, internal medicine, oncology, intensive care, gastroenterology and geriatrics) in Austria, the Czech Republic, Egypt, Germany, Hungary, Lebanon, Libya, Poland, Romania, Slovakia, Spain and Switzerland. Being a prospective cohort study, randomly selected adult patients were included at admission and followed during their hospitalisation. Data were collected on the nutritional risk screening, complications, mortality, length of stay and discharge. The correlation between risk status and clinical outcome was assessed and adjusted for confounders (age, speciality, diagnoses, comorbidity, surgery, cancer and region) by multivariate regression analysis. RESULTS: Of the 5051 study patients, 32.6% were defined as 'at-risk' by NRS-2002. 'At-risk' patients had more complications, higher mortality and longer lengths of stay than 'not at-risk' patients and these variables were significantly related to components of NRS-2002, also when adjusted for confounders. CONCLUSIONS: Components of NRS-2002 are independent predictors of poor clinical outcome.

Abstract: OBJECTIVE: We tested the feasibility of using the Nutritional Risk Screening 2002 tool among hospitalized medical patients in Beijing and Baltimore and determined the prevalence of nutritional risk, nutritional support, and nutritional risk changes from admission to discharge or over a 2-wk period. METHODS: A comparative design was used to compare data collected at Beijing and Baltimore teaching hospitals from April 2006 to April 2007. A total of 500 consecutive medical patients, 300 from Beijing and 200 from Baltimore, who met the inclusion criteria on admission and provided informed consent were enrolled. RESULTS: Among the hospitalized patients, 94.0% in Beijing and 99.5% in Baltimore were able to complete the Nutritional Risk Screening 2002. Prevalences of nutritional risk were 39.0% and 51.0%, respectively (P < 0.05). For the patients at nutritional risk, only 17.9% in Beijing and 14.7% in Baltimore used parenteral nutrition or enteral nutrition (P = 0.518). For non-risk patients, 3.3% in Beijing used nutritional support, whereas no patient in Baltimore used this support (P = 0.095). Prevalences of nutritional risk changed from 39.0% to 38.5% (P = 0.892) during hospitalization in Beijing and from 51.0% to 41.4% in Baltimore (P = 0.055). CONCLUSION: The Nutritional Risk Screening 2002 was feasible in the Beijing and Baltimore teaching hospitals. The prevalence of nutritional risk observed in Baltimore was higher than that in Beijing. No difference was observed in the application rate of nutritional support and changes in nutritional risk during hospitalization between these two hospitals.

Abstract: BACKGROUND: A combination of tyrosine, capsaicin, catechines and caffeine may stimulate the sympathetic nervous system and promote satiety, lipolysis and thermogenesis. In addition, dietary calcium may increase fecal fat excretion. OBJECTIVE: To investigate the acute and subchronic effect of a supplement containing the above mentioned agents or placebo taken t.i.d on thermogenesis, body fat loss and fecal fat excretion. DESIGN: In total, 80 overweight-obese subjects ((body mass index) 31.2+/-2.5 kg/m(2), mean+/-s.d.) underwent an initial 4-week hypocaloric diet (3.4 MJ/day). Those who lost>4% body weight were instructed to consume a hypocaloric diet (-1.3 MJ/day) and were randomized to receive either placebo (n=23) or bioactive supplement (n=57) in a double-blind, 8-week intervention. The thermogenic effect of the compound was tested at the first and last day of intervention, and blood pressure, heart rate, body weight and composition were assessed. RESULTS: Weight loss during the induction phase was 6.8+/-1.9 kg. At the first exposure the thermogenic effect of the bioactive supplement exceeded that of placebo by 87.3 kJ/4 h (95%CI: 50.9;123.7, P=0.005) and after 8 weeks this effect was sustained (85.5 kJ/4 h (47.6;123.4), P=0.03). Body fat mass decreased more in the supplement group by 0.9 kg (0.5; 1.3) compared with placebo (P<0.05). The bioactive supplement had no effect on fecal fat excretion, blood pressure or heart rate. CONCLUSION: The bioactive supplement increased 4-h thermogenesis by 90 kJ more than placebo, and the effect was maintained after 8 weeks and accompanied by a slight reduction in fat mass. These bioactive components may support weight maintenance after a hypocaloric diet.

Abstract: BACKGROUND: Undernutrition in hospitals is a common problem associated with increased morbidity and mortality, prolonged convalescence and duration of hospital stay and increased health care costs. During recent years several initiatives have brought hospital undernutrition into focus and guidelines and standards have been published. In 1997, a questionnaire-based survey among Danish hospital doctors and nurses in selected departments concluded that clinical nutrition did not fulfil accepted standards. AIMS: We wished to determine if improvements had occurred in the intervening period. METHOD: Thus, in 2004 a similar questionnaire was sent to 4000 randomly selected Danish hospital doctors and nurses and responses were compared to those from 1997. The questionnaire dealt with attitudes and practice in the areas of nutritional screening, treatment plan, monitoring as well as with knowledge, education, tools and guidelines, organisation and possible barriers to implementation of nutritional screening and therapy. RESULTS: The overall response rate was 38%. We observed a marked improvement especially in screening procedures, calculation of energy intake in at-risk patients and local availability of guidelines. Many departments had appointed staff members with special interest and knowledge in clinical nutrition. CONCLUSION: Although significant positive changes had thus occurred, the main barriers against implementation of good nutrition care continued to be lack of knowledge, interest and responsibility, in combination with difficulties in making a nutrition plan. This will be the focus of future activities.

Abstract: The ESPEN guidelines on enteral nutrition are the first evidence-based European recommendations for enteral nutrition. They were established by European experts for a variety of disease groups. During guideline development it became evident that terms and definitions in clinical nutrition have been used inconsistently depending on medical disciplines as well as regional and personal preferences. Therefore, to increase explanatory accuracy it was necessary to unify them. In this chapter terms and definitions used throughout all guidelines are explained. Additionally answers to more general questions, which might be important in most indications are dealt with, i.e. use of fibre containing and diabetes formulae.

Abstract: BACKGROUND AND AIMS: Many barriers make implementation of nutritional therapy difficult in hospitals. In this study we investigated whether, a targeted plan made by the staff in different departments could improve nutritional treatment within selected quality goals based on the ESPEN screening guidelines. METHODS: The project was carried out as a continuous quality improvement project. Four different specialities participated in the study with a nutrition team of both doctors, nurses, and a dietician, and included the following methods: (1) Pre-measurement: assessment of quality goals prior to study including the use of screening of nutritional risk (NRS-2002), whether a nutrition plan was made, and monitoring was documented in the records. (2) Intervention: multidisciplinary meeting for the ward staff using a PC-based meeting system for detecting barriers in the department concerning nutrition, elaboration of an action plan and implementation of the plan. (3) Re-measurement: as in (1) based on information from records and patient interviews, and an evaluation based on focus group interview with the staff. Patients who gave informed consent to participate in the study (>14 years) were included consecutively. Mann-Whitney and Kruskal-Wallis test was used for ordinal data, and Pearson chi(2) test for nominative data. P values <0.05 were considered significant. The study was performed in accordance with the Research Ethics Committee. RESULTS: In this study 141/122 patients were included before/after the implementation period with a mean weight loss within the last 3 months of 6.2 and 5.2 kg, respectively. Before the study we found that BMI was not measured. More than half of the patients had a weight loss within the last 3 months, and 40% had a weight loss during hospitalization, and this was not documented in the records. About 75% had a food intake less than normal within the last week, and nearly one-third were at a severe nutritional risk, and only 33% of these had a nutrition plan, and 18% a plan for monitoring. Barriers concerning nutrition included low priority, no focus, no routine or established procedures, and insufficient knowledge, lack of quality and choice of menus, and lack of support from general manager of the hospital. The staff introduced individually targeted procedures including assigning of responsibility, a nutrition record, electronic calculator of energy intake, upgrading of the dieticians and special diets, communication, and educational programs. A great consistency existed between barriers for targeted nutrition effort and ideas for improvement of the quality goals between the different departments. Quality assessment after study showed an overall significant improvement of the selected quality goals. CONCLUSION: The introduction of a new method for implementation of nutritional therapy according to ESPEN screening guidelines seems to improve nutritional therapy in hospitals. The method included assessment of quality goals, identification of barriers and individual targeted plans for each department followed by an evaluation process. The model has to be refined further with relevant clinical endpoints.

Abstract: The concept of malnutrition in the geriatric population describes a deficient state of energy and nutrient intake with harmful clinical consequences. Despite of having a significant effect on morbidity and mortality, there are no generally accepted criteria for diagnosing malnutrition in the elderly. With increasing age the general recognition of the nutritional status becomes more important for the diagnosis of malnutrition than isolated parameters. Recording a patient"s history must include any weight loss and changes in appetite. Reasons for a diminished nutritional intake must be explored systematically as well. As part of physical examination one has to pay attention to clinical signs of malnutrition (general muscular atrophy, loss of subcutaneous fat) and to signs of micronutrient deficiencies. The documentation of oral intake can supply important evidence for deficient intake of energy and nutrients. Of special relevance among anthropometric values are a BMI of less than 20 kg/m and calf circumference of less than 31 cm. Individual follow-up data are superior to isolated measurements Laboratory diagnostic tests (for example albumin) are of minor importance for the diagnosis of malnutrition because of their low specificity. As a consequence of unsolved methodical problems, bioelectrical impedance analysis can currently be recommended only to those who are experienced with this method and its limitations. Screening and assessment tools like Mini Nutritional Assessment (MNA) and Nutritional Risk Screening(NRS) are helpful for a quick and simple identification of malnourished patients and those who are at risk. The MNA is especially applicable for people who live independently and for cooperative residents of nursing homes. The NRS is a valuable alternative for hospital patients and those unable to cooperate. Screening for malnutrition should be routine practice in the elderly population, especially for those at high risk for it like in hospitals and in nursing homes.

Abstract: Enteral nutrition (EN) by means of oral nutritional supplements (ONS) and tube feeding (TF) offers the possibility to increase or to insure nutrient intake in case of insufficient oral food intake. The present guideline is intended to give evidence-based recommendations for the use of ONS and TF in patients with liver disease (LD). It was developed by an interdisciplinary expert group in accordance with officially accepted standards and is based on all relevant publications since 1985. The guideline was discussed and accepted in a consensus conference. EN by means of ONS is recommended for patients with chronic LD in whom undernutrition is very common. ONS improve nutritional status and survival in severely malnourished patients with alcoholic hepatitis. In patients with cirrhosis, TF improves nutritional status and liver function, reduces the rate of complications and prolongs survival. TF commenced early after liver transplantation can reduce complication rate and cost and is preferable to parenteral nutrition. In acute liver failure TF is feasible and used in the majority of patients.

Abstract: The prevalence of disease-related malnutrition is high among surgical patients, and the condition tends to worsen during hospital stay due to an inadequate dietary intake. The etiology is mechanical obstruction in many cases but also the endocrine condition of stress-metabolism plays a significant role. Several randomized studies and metaanalyses have indicated that clinical outcome improves with adequate nutrition support. Despite this evidence, recent studies indicate that little is done in daily clinical practice. A combined effort from hospital managers, doctors, nurses and clinical dieticians is required to improve this care gap.

Abstract: BACKGROUND AND AIMS: Hospital malnutrition is prevalent, but nutritional practice in hospitals has a low priority. To improve the quality in nutritional routine, ESPEN has developed standards to improve the inadequate and insufficient nutritional treatments seen today. However, there is a discrepancy between the standards and clinical practice. This study was conducted to investigate nutritional practice in different hospital settings in relation to these standards (e.g.: screening of all patients, assessment of at-risk patients) among Scandinavian doctors and nurses. METHODS: A questionnaire about nutritional attitudes and routine was mailed to doctors and nurses in Denmark, Sweden and Norway. RESULTS: Altogether, 4512 (1753 doctors, 2759 nurses) answered the questionnaire. Both screening and assessment of at-risk patients differ between the countries. Nutritional screening was more common in Denmark (40%), compared to Sweden (21%) and Norway (16%). Measuring dietary intake in nutritional at-risk patients was more common in Denmark (46%), compared to Sweden (37%) and Norway (22%). However, all countries agreed that nutritional screening (92%, 88%, 88%) and measuring dietary intake (97%, 95%, 97%) were important, Denmark, Sweden and Norway, respectively. CONCLUSION: There is a large discrepancy between nutritional attitudes and practice. The standards suggested from the ESPEN are not fulfilled.

Abstract: This chapter will focus on studies within the last 5 years of nutrition in end stage liver disease, but earlier studies illustrating the present state of affairs will also be mentioned. The first part will focus on descriptive epidemiological studies that help to set the scene for the intervention studies, which will be described in the second part. Each part will discuss liver cirrhosis, acute liver failure and liver transplantation separately. The aim is to provide the reader with sufficient background for the decision in clinical practice about when to see nutrition support as an important part of treatment of the patient.

Abstract:

Abstract: BACKGROUND & AIMS: Undernourished patients have an increased risk of complications and a prolonged hospital stay, compared to those who are not undernourished. The aim of this study was to evaluate the effect of nutritional intervention in a random sample of hospitalized patients at nutritional risk. METHODS: A randomized, controlled trial of nutritional intervention in 212 patients. Intervention consisted of a specialized nutritional team (nurse and dietician) who attended patients and staff for motivation, detailed a nutritional plan, assured delivery of prescribed food and gave advice on enteral or parenteral nutrition when appropriate. The control group received the standard regime used in the department. The primary endpoint was the part of the length of stay (LOS) that was considered to be sensitive to nutritional support, designated LOSNDI. The nutritional discharge index (NDI) consists of three objective criteria: (1) the patient is able to manage toilet visits without assistance, reflecting mobilization; (2) the patient is without fever (tp < 38 degrees C), reflecting absence of infection; and (3) the patient has no intravenous access, reflecting absence of complications in general. On the day when all three criteria were fulfilled, hospital stay was no longer considered to be sensitive to nutritional support. Actual LOS is also reported. Incidence and severity of complications were recorded to explain LOSNDI findings. As a secondary endpoint, quality of life was evaluated by the Short Form 36 (SF-36) questionnaire. RESULTS: Intervention led to an intake of > or = 75% of requirements in 62% of the intervention patients, as compared to 36% of the control patients. Rates of complications, mean LOSNDI and LOS were not significantly different between the two study groups. However, among patients with complications a difference in LOSNDI between intervention patients (14 +/- 2 days, mean +/- SE) and control patients (20 +/- 2 days) was statistically significant (P = 0.015). In the same patients, LOS was 17 +/- 2 days in the intervention group and 22 +/- 2 days in the control group (P = 0.028). The SF-36 questionnaire did not show a significant effect of treatment. CONCLUSIONS: Protein and energy intake of nutritionally at-risk patients was increased which resulted in shortening of the part of the length of stay that was considered to be sensitive to nutritional support (LOSNDI) and shorter length of stay (LOS) among patients with complications.

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Abstract: BACKGROUND & AIMS: Undernutrition is associated with increased morbidity and mortality and is common in patients admitted to hospital. We examined (1) the prevalence of patients at nutritional risk, (2) whether these patients were identified by the staff, and (3) whether a nutritional plan and monitoring was made for patients at nutritional risk. METHODS: A cross-sectional study in 15 randomly selected departments (>200 beds, departments of internal medicine, gastro- and orthopedic surgery) in Danish hospitals. The patients were characterized by scoring the components 'undernutrition' and 'severity of disease' in 4 categories (absent, mild, moderate or severe). The patient could have a score of 0-3 for each component (undernutrition and severity of disease), and any patient with a total score > or = 3 was considered at nutritional risk. Undernutrition was evaluated by 3 variables (BMI, recent weight loss, recent food intake). RESULTS: Out of 590 patients, 39.9% were nutritionally at risk, with the highest prevalence in departments of gastro-surgery (57%). BMI was <18.5 in 10.9%, and between 18.5 and 20.5 in 16.7% of the patients. In 7.6% the records contained information about nutritional risk, in 14.2% about a nutrition plan of which only 55.2% included a plan for monitoring. Measurements of BMI were found in 3% of the records. Both severity of disease (P < 0.02) and weightloss (P < 0.04) were predictive for making a nutrition plan. CONCLUSIONS: Nearly 40% of patients in departments of internal medicine, gastro- and orthopedic surgery are at nutritional risk, and only a minor part of these patients are identified. As a consequence only few patients at a nutritional risk have a nutrition plan and a plan for monitoring.

Abstract: Several studies suggested that branched-chain amino acids (BCAA) improve plasma amino acid imbalance as well as protein metabolism in patients with cirrhosis. However, commercial formulas supplemented with free BCAA have their limitations. We evaluated a modified soy protein diet with covalently bound BCAA (diet M) by comparing it with diets based on casein (diet C) or Hepatic Aid II (diet H; commercial formula) as protein sources. After 3 weeks of bile duct obstruction, 24 Sprague-Dawley rats divided into three groups received diets with 9% (w/w) protein/amino acids for 7 days. Nutritional and clinical parameters were determined. Nitrogen balance and weight gain (g)/protein intake (g) with diet M (0.19 +/- 0.31 and 1.33 +/- 1.43 g, respectively) were significantly higher (p < 0.05) than with diet H (-0.34 +/- 0.20 and -0.34 +/- 1.11 g), but comparable to those with diet C (0.04 +/- 0.38 and 0.20 +/- 0.93 g). Animals on diet M had a significantly (p < 0.05) increased plasma BCAA:aromatic amino acid ratio (1.8 +/- 0.3) as compared with those on diets H (1.3 +/- 0.1) and C (0.8 +/- 0.0). There were no significant differences in organ weight or liver function among the groups. We conclude that the BCAA-modified protein is an attractive option in the nutritional support of patients having cirrhosis.

Abstract: BACKGROUND & AIMS: A system for screening of nutritional risk is described. It is based on the concept that nutritional support is indicated in patients who are severely ill with increased nutritional requirements, or who are severely undernourished, or who have certain degrees of severity of disease in combination with certain degrees of undernutrition. Degrees of severity of disease and undernutrition were defined as absent, mild, moderate or severe from data sets in a selected number of randomized controlled trials (RCTs) and converted to a numeric score. After completion, the screening system was validated against all published RCTs known to us of nutritional support vs spontaneous intake to investigate whether the screening system could distinguish between trials with a positive outcome and trials with no effect on outcome. METHODS: The total number of randomized trials identified was 128. In each trial, the group of patients was classified with respect to nutritional status and severity of disease, and it was determined whether the effect of nutritional intervention on clinical outcome was positive or absent. RESULTS: Among 75 studies of patients classified as being nutritionally at-risk, 43 showed a positive effect of nutritional support on clinical outcome. Among 53 studies of patients not considered to be nutritionally at-risk, 14 showed a positive effect (P=0.0006). This corresponded to a likelihood ratio (true positive/false positive) of 1.7 (95% CI: 2.3-1.2). For 71 studies of parenteral nutrition, the likelihood ratio was 1.4 (1.9-1.0), and for 56 studies of enteral or oral nutrition the likelihood ratio was 2.9 (5.9-1.4). CONCLUSION: The screening system appears to be able to distinguish between trials with a positive effect vs no effect, and it can therefore probably also identify patients who are likely to benefit from nutritional support.

Abstract: AIM: To provide guidelines for nutrition risk screening applicable to different settings (community, hospital, elderly) based on published and validated evidence available until June 2002. NOTE: These guidelines deliberately make reference to the year 2002 in their title to indicate that this version is based on the evidence available until 2002 and that they need to be updated and adapted to current state of knowledge in the future.In order to reach this goal the Education and Clinical Practice Committee invites and welcomes all criticism and suggestions (button for mail to ECPC chairman).

Abstract: Hyperammonemia and hyperventilation are consistent findings in patients with fulminant hepatic failure (FHF), which may interfere with cerebral glucose and oxygen metabolism. The aim of the present study is to evaluate whether cerebral oxidative metabolism is preserved early in the course of FHF and whether hyperventilation has an influence on this. We included 16 patients with FHF, 5 patients with cirrhosis of the liver, and 8 healthy subjects. Concomitant blood sampling from an arterial catheter and a catheter in the jugular bulb and measurement of cerebral blood flow by the xenon 133 wash-out technique allowed calculation of cerebral uptake of glucose (CMRgluc) and oxygen (CMRO2). Both CMRgluc and CMRO2 were reduced in patients with FHF compared with those with cirrhosis and healthy subjects, i.e., 11.8 +/- 2.7 v 18.3 +/- 5.5 and 28.5 +/- 6.6 micromol/100 g/min (P <.05) and 86 +/- 18 v 164 +/- 42 and 174 +/- 27 micromol/100 g/min (P <.05). Arteriovenous difference in oxygen and oxygen-glucose index were normal in patients with FHF. Institution of mechanical hyperventilation did not affect glucose and oxygen uptake and hyperventilation did not affect lactate-pyruvate ratio or lactate-oxygen index. In conclusion, we found that cerebral glucose and oxygen consumption are proportionally decreased in patients with FHF investigated before clinical signs of cerebral edema. Our data suggest that cerebral oxidative metabolism is retained at this stage of the disease without being compromised by hyperventilation.

Abstract: Fulminant hepatic failure (FHF) is often complicated by high intracranial pressure (ICP) and fatal brain damage. In this study, we determined if a rise in [glutamate]ec and [lactate]ec preceded surges of high ICP in patients with FHF (median age, 42; range, 20-55 years; 7 women; 3 men) by inserting a microdialysis catheter into the brain-cortex together with an ICP catheter. The microdialysis catheter was perfused with artificial cerebrospinal-fluid at a rate of 0.3 microL/min. Dialysate was collected approximately every 30 minutes or when ICP increased. A total of 352 microdialysis samples were collected during a median of 3 days and allowed for approximately 1,760 bedside analyses of the collected dialysate. In 5 patients that later developed surges of high ICP, the initial values of [glutamate]ec and [lactate]ec were 2 to 5 times higher compared with patients with normal ICP. [Glutamate]ec then tended to vanish with time in both groups of patients. An increase in [glutamate]ec did not precede high ICP in any of the cases. In contrast, [lactate]ec was high throughout the study in the high ICP group and increased further before surges of high ICP. We conclude that in patients with FHF, cerebral [glutamate]ec and [lactate]ec are elevated. However, the elevated [glutamate]ec is not correlated to high ICP. In contrast, elevations in [lactate]ec preceded surges of high ICP. In conclusion, accelerated glycolysis with lactate accumulation is implicated in vasodilatation and high ICP in patients with FHF. The data suggest that bedside cerebral microdialysis is a valuable tool in monitoring patients with FHF and severe hyperammonemia.

Abstract: BACKGROUND AND AIMS: Many patients in hospitals are undernourished and nutritional care is inadequate in most hospitals. The aim of this investigation was to gain insight into how this situation could be improved. METHODS: Seven hundred and fifty randomly selected patients were screened at admission in three hospitals and surveyed during their entire hospitalization. Each time a patient was not treated according to a clearly defined nutritional standard, the nurse responsible for the patient was interviewed about possible reasons according to preformed questionnaires. RESULTS: The investigators found that 22% of the patients were nutritionally at-risk, and that only 25% of these patients received an adequate amount of energy and protein. The departments had only screened for nutritional problems in 60% of the cases. Only 47% of the patients, who the departments judged to be at-risk patients, had a nutrition plan worked out, and only about 30% of the at-risk patients were monitored by the departments by recording of dietary intake and/or body weight. The main causes for inadequate nutritional care were lack of instructions to deal with these problems, and lack of basic knowledge with respect to dietary requirements and practical aspects of the hospital's food provision. Patient-related aspects and the system of food provision also contributed, but only to a small degree. CONCLUSIONS: These findings form the basis of the strategy to improve nutritional care in these hospitals.

Abstract: OBJECTIVE: In acute liver failure (ALF), urea production is severely impaired, and detoxification of ammonia by glutamine synthesis plays an important protective role. The aim of this study was to examine the effects of therapeutic high-volume plasmapheresis (HVP) on arterial concentrations and splanchnic exchange rates of ammonia, urea, and amino acids-in particular, glutamine. METHODS: A quantity of 8 L of plasma was exchanged over the course of 7 h in 11 patients with ALF after development of hepatic encephalopathy grade III-IV. Splanchnic exchange rates of ammonia, urea, and amino acids were measured by use of liver vein catheterization. RESULTS: HVP removed ammonia and glutamine at a rate of 1 micromol/min and 27 micromol/min, respectively. Arterial ammonia decreased from 160 +/- 65 to 114 +/- 50 micromol/L (p < 0.001). In contrast, arterial glutamine was only minimally changed from 1791 +/- 1655 to 1764 +/- 1875 micromol/L (NS). This implied that the rate of systemic glutamine synthesis was increased by 27 micromol/min. Splanchnic exchange rates (before vs after HVP) were as follows: for ammonia, -93 +/- 101 versus -70 +/- 80 micromol/min (NS); urea-nitrogen, 0.08 +/- 1.64 versus -0.31 +/- 0.45 mmol/min (NS); alanine, -73 +/- 151 versus 12 +/- 83 micromol/min (p < 0.05); and glutamine: 132 +/- 246 versus 186 +/- 285 micromol/min (NS), with negative values denoting release. CONCLUSIONS: Arterial ammonia decreased during HVP in patients with ALF. The data suggest that this effect of HVP could be explained by increased hepatic urea synthesis and possibly by increased glutamine synthesis in muscle tissue.

Abstract: BACKGROUND & AIMS: High circulating levels of ammonia have been suggested to be involved in the development of cerebral edema and herniation in fulminant hepatic failure (FHF). The aim of this study was to measure cerebral metabolism of ammonia and amino acids, with special emphasis on glutamine metabolism. METHODS: The study consisted of patients with FHF (n = 16) or cirrhosis (n = 5), and healthy subjects (n = 8). Cerebral blood flow was measured by the 133Xe washout technique. Blood samples for determination of ammonia and amino acids were drawn simultaneously from the radial artery and the internal jugular bulb. RESULTS: A net cerebral ammonia uptake was only found in patients with FHF (1.62 +/- 0.79 micromol x 100 g(-1) x min(-1)). The cerebral glutamine efflux was higher in patients with FHF than in the healthy subjects and cirrhotics, -6.11 +/- 5.19 vs. -1.93 +/- 1.17 and -1.50 +/- 0.29 micromol x 100 g(-1) x min(-1), respectively (P < 0.05). Patients with FHF who subsequently died of cerebral herniation (n = 6) had higher arterial ammonia concentrations, higher cerebral ammonia uptake, and higher cerebral glutamine efflux than survivors. Intervention with short-term mechanical hyperventilation in FHF reduced the net cerebral glutamine efflux, despite an unchanged net cerebral ammonia uptake. CONCLUSIONS: Patients with FHF have an increased cerebral glutamine efflux, and short-term hyperventilation reduces this efflux. A high cerebral ammonia uptake and cerebral glutamine efflux in patients with FHF were associated with an increased risk of subsequent fatal intracranial hypertension.

Abstract: BACKGROUND & AIMS: In patients with acute liver failure, hyperammonemia is associated with cerebral herniation. We examined the splanchnic and leg exchange of amino acids, urea, and ammonia in such patients. METHODS: Bedside liver vein catheterization was used in 22 patients after development of hepatic encephalopathy grades III-IV. Femoral venous blood was sampled in 7 of these patients. RESULTS: Arterial amino acid concentration (8.1 +/- 4.1 mmol/L) was increased 4-fold above normal. Glutamine (2.4 +/- 1.8 mmol/L) and alanine (0.57 +/- 0.35 mmol/L) were by far the predominant amino acids exchanged in the splanchnic and leg circulation. In the splanchnic circulation, there was a net uptake of glutamine (241 +/- 353 micromol/min) and ammonia and alanine were released in an almost 1:1 stoichiometry (r(2) = 0.47; P < 0.001). In the leg, ammonia and alanine were removed and glutamine released. The leg ammonia concentration difference was correlated to that of glutamine (r(2) = 0.80; P = 0.008) and alanine (r(2) = 0.67; P = 0.03). CONCLUSIONS: Splanchnic metabolism of glutamine in combination with decreased hepatic function was responsible for the splanchnic release of ammonia and alanine. These processes were reversed in skeletal muscle. Stimulation of skeletal muscle metabolism of ammonia could be a important target for future treatment of patients with acute liver failure.

Abstract: Specific nutrition standards have now been developed by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO). We investigated the use of clinical nutrition in Danish hospitals and compared it with the standards of JCAHO by doing a questionnaire-based investigation among doctors and nurses randomly selected in 40 hospitals. Overall, 857 (43.4%) responded to the questionnaire (doctors: 395, nurses: 462). Forty percent found it difficult to identify risk-patients, and 52% needed specific screening tools. Eighty-four percent found that a nutrition plan should be described in the patient record, but 39% found it difficult to set up an individual plan, and 79% expressed a need for specific guidelines. The use of clinical nutrition in Danish hospitals did not fulfill the standards for nutrition support according to the criteria established by JCAHO. Special efforts should be aimed at education, specific screening tools and introduction of guidelines in clinical nutrition.

Abstract: BACKGROUND/AIMS: This study aimed to characterize the exchange of fuel substrates in the splanchnic circulation in acute liver failure. METHODS: Liver vein catheterization was used in 22 patients with acute liver failure after development of hepatic encephalopathy grade III-IV Healthy controls, patients with cirrhosis and patients with acute on chronic liver disease were also studied. RESULTS: In acute liver failure there was splanchnic removal of glucose (0.21+/-0.44 mmol/min), release of lactate (0.34+/-0.37 mmol/min), pyruvate (0.08+/-0.06 mmol/min) and ketone bodies (0.04+/-0.02 mmol/min), while extraction of amino acids and free fatty acids was insignificant. In the acute liver failure group, a normal hepatic venous oxygen saturation (0.69+/-0.12) and normal pyruvate/lactate ratio suggested absence of hypoxia even though the acetoacetate/beta-hydroxybutyrate ratio was decreased. Only in the acute liver failure group did the measured splanchnic oxygen content difference exceed what could be accounted for even by hypothesizing complete oxidation of all extracted blood-borne fuel substrates; oxidation of endogenous substrates may be quantitatively important in this condition. CONCLUSION: Acute liver failure was associated with a state of accelerated glycolysis in the splanchnic region, leading to release of lactate in the absence of splanchnic hypoxia.

Abstract: Cerebral edema leading to cerebral herniation (CH) is a common cause of death in acute liver failure (ALF). Animal studies have related ammonia with this complication. During liver failure, hepatic ammonia removal can be expected to determine the arterial ammonia level. In patients with ALF, we examined the hypotheses that high arterial ammonia is related to later death by CH, and that impaired removal in the hepatic circulation is related to high arterial ammonia. Twenty-two patients with ALF were studied retrospectively. In addition, prospective studies with liver vein catheterization were performed after development of hepatic encephalopathy (HE) in 22 patients with ALF and 9 with acute on chronic liver disease (AOCLD). Cerebral arterial-venous ammonia difference was studied in 13 patients with ALF. In all patients with ALF (n = 44), those who developed CH (n = 14) had higher arterial plasma ammonia than the non-CH (n = 30) patients (230 +/- 58 vs. 118 +/- 48 micromol/L; P <. 001). In contrast, galactose elimination capacity, bilirubin, creatinine, and prothrombin time were not different (NS). Cerebral arterial-venous differences increased with increasing arterial ammonia (P <.001). Arterial plasma ammonia was lower than hepatic venous in ALF (148 +/- 73 vs. 203 +/- 108 micromol/L; P <.001). In contrast, arterial plasma ammonia was higher than hepatic venous in patients with AOCLD (91 +/- 26 vs. 66 +/- 18 micromol/L; P <.05). Net ammonia release from the hepatic-splanchnic region was 6.5 +/- 6. 4 mmol/h in ALF, and arterial ammonia increased with increasing release. In contrast, there was a net hepatic-splanchnic removal of ammonia (2.8 +/- 3.3 mmol/h) in patients with AOCLD. We interpret these data that in ALF in humans, vast amounts of ammonia escape hepatic metabolism, leading to high arterial ammonia concentrations, which in turn is associated with increased cerebral ammonia uptake and CH.

Abstract: Specific nutrition standards are now developed by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) in order to improve the nutritional status in hospitalized patients. We investigated the use of clinical nutrition in Danish hospitals and compared it with the standards of JCAHO by doing a questionnaire-based investigation among doctors and nurses randomly selected in 40 hospitals including internal medicine, gastroenterology, oncology, orthopedic departments and intensive care units (ICU).Overall, 857 (43.4%) responded to the questionnaire (doctors: 395, nurses: 462). Seventy-seven percent stated that nutritional assessment ought to be performed on admission, but only 24% stated that it was a routine procedure. Forty percent found it difficult to identify risk-patients, and 52% needed specific screening tools. Twenty-two percent registered body weight in all patients, and 18% registered nutrient intake routinely. Eighty-four percent found that a nutrition plan should be described in the patient record, but 39% found it difficult to set up an individual plan, and 79% expressed a need for specific guidelines. Eighty-four percent would only accept a patient being on isotonic glucose and/or electrolyte infusion for < 5 days (42% for < 2 days), and 33% would only accept a weight loss of 5% before active nutrition was initiated. About 50% would be restrictive in supplying enteral or parenteral nutrition to patients with impaired liver or kidney function. Twenty-seven percent did not use active nutritional therapy at all. Seventy-six percent found that nutritional assessment should be performed during hospital stays, but only 23% monitored the nutritional status. Sixty-eight percent stated that responsibility should be assigned to one or more persons, but this was the case in only 20%The use of clinical nutrition in Danish hospitals did not fulfill the standards for nutrition support according to the criteria established by JCAHO. Special efforts should be aimed at education, specific screening tools and introduction of guidelines in clinical nutrition.

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Abstract: Patients with cirrhosis of the liver require an increased amount of protein to achieve N balance. However, the utilization of protein with increased protein intake, i.e. the slope from regression analysis of N balance v. intake, is highly efficient (Nielsen et al. 1995). In the present study, protein requirement and protein utilization were investigated further by measuring protein synthesis and degradation. In two separate studies, five or six patients with cirrhosis of the liver were refed on a balanced diet for an average of 2 or 4 weeks. Protein and energy intakes were doubled in both studies. Initial and final whole-body protein metabolism was measured in the fed state by primed continuous [15N]glycine infusion. Refeeding caused a statistically significant increase of about 30% in protein synthesis in both studies while protein degradation was only slightly affected. The increase in protein synthesis was associated with significant increases in plasma concentrations of total amino acids (25%), leucine (58%), isoleucine (82%), valine (72%), proline (48%) and triiodothyronine (27%) while insulin, growth hormone, insulin-like growth factor (IGF)-I and IGF-binding protein-3 were not changed significantly. The results indicate that the efficient protein utilization is due to increased protein synthesis, rather than decreased protein degradation, and suggest that increases in plasma amino acids may be responsible for the increased protein synthesis. A comparison of the patients who had a normal protein requirement with the patients who had an increased protein requirement suggests that the increased protein requirement is due to a primary increase in protein degradation. It is speculated that this is due to low levels of IGF-I secondary to impaired liver function, since initial plasma concentration of IGF-I was about 25% of control values and remained low during refeeding.

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Abstract: The purpose of the study was to evaluate the feasibility of nutritional therapy in a university hospital. Over a four-year period, 542 adult patients from 16 different departments were included in the study due to malnutrition and/or severe disease. Energy requirement including a surplus for weight gain was calculated by the factorial method and feeding was undertaken by means of food, liquid supplements, tube feeding or parenteral nutrition for an average period of 4.8 weeks. In patients with benign disease only, the average weight gain was as expected from energy balance but in patients with a benign stress-catabolic disease weight gain was only 40% of that expected. In malnourished patients with malignant disease, radiation- or chemotherapy could be carried out without further loss of body weight. During bone-marrow transplantation only a minor weight loss occurred. In conclusion, nutritional therapy is feasible in a clinical setting and the methods employed can identify groups of patients that require only nutritional support and other groups of patients that in addition require treatment of a stress-catabolic state.

Abstract: Body composition was determined by dual energy X-ray absorptiometry (DXA) scanning and classical reference methods (40K, 3H2O, and a combination of these in a four-compartment model) in 19 overweight patients with rheumatoid arthritis who underwent a 12-week weight-reducing regimen. The aim of the study was to investigate whether DXA provides a valid estimate of body composition. The results showed that weight as determined by DXA was highly significantly correlated to weight determined by scales. Furthermore, significant correlations were found in the body components (fat-free mass, fat mass) determined by DXA, 40K, 3H2O and the four-compartment model. Mean values differed slightly but significantly. With respect to changes in body composition, no significant correlations were found between any of the methods, except for the weight loss recorded by DXA and scales, and loss of fat mass (and fat free mass) estimated by 3H2O and the four-compartment model. The sparseness of correlations reflected the small changes in fat-free mass and fat mass (2.6 and 1.7 kg respectively), and the fact that changes were comparable to measurement errors of the various methods. We suggest that DXA scanning is a valid supplement for determination of body composition. Validation of DXA scanning requires new experimental in vitro investigations, which, incidentally, also applies to the classical reference methods.

Abstract: OBJECTIVE: To reduce body weight in obese patients with rheumatoid arthritis (RA) without loss of body cell mass (BCM) and without impairment of physical performance. METHODS: Nineteen overweight RA patients were studied before, during, and after a 12-week weight reducing regime consisting of reduced dietary energy intake, supplemented with a high-protein-low-energy powder preparation, and moderate physical training. Body composition was measured by a four compartment method, which by combining determinations of total body water and total body potassium allows a distinction between the two variable components of fat free mass (FFM): BCM and extracellular water (ECW). Physical fitness was measured by a bicycle exercise test. RESULTS: Mean weight loss during the study was 4.5 kg. The patients lost 9% of their initial fat mass, 3% of initial BCM and 5% of initial ECW. Physical fitness was slightly, but significantly, improved. CONCLUSION: The regime described was successful in achieving a significant weight loss with minimal loss of BCM and maintenance of physical fitness.

Abstract: Repeated episodes of hypoglycaemia were observed in two girls with spinal muscular atrophy. During a 12 h fast blood glucose fell to 3.4 and 2.7 mmol/L, respectively. One girl developed hypoglycaemia and ketonuria. Reduced gluconeogenesis was probably the cause of hypoglycaemia in these patients who had a muscle mass of about 10% of bodyweight (normal 30-40%). Hypoglycaemia must be suspected and treated when patients with severe muscle wasting due to chronic neuromuscular disorders are admitted comatose. In our experience this condition is often regarded as respiratory insufficiency.

Abstract: A previous study has shown that malnourished, clinically stable patients with liver cirrhosis are in protein and energy balance at their spontaneous dietary intake and that an improvement in nutritional status cannot be anticipated at this intake (Nielsen et al. 1993). In the present study we examined to what extent oral intake could be increased by nutritional support, and to what extent dietary protein would be retained with increased intake. The techniques used for balance studies were also validated since this information is not available for patients with liver cirrhosis. Fifteen malnourished patients with alcoholic liver cirrhosis were given increasing amounts of a balanced ordinary diet for 38 (SE 3) d. Intakes of protein and energy were recorded by weighing servings and leftovers on food trays. Protein intake was calculated from food tables. Total N disposal was calculated after measurement of urinary N excretion, and protein balance was calculated from the N balance. A validation study of protein balance in a subgroup of patients (analysis of N in food by the duplicate portion technique, correction for incomplete recovery of urine by measurement of urinary para-aminobenzoic acid (PABA) after administration of PABA tablets, and measurement of faecal N) did not change protein balance values. Protein intake increased from 1.0 (SE 0.1) g/kg per d to 1.8 (SE 0.1) g/kg per d. With increasing protein intake, 84 (SE 8)% of the increase in intake was retained. The rate of protein retention was not saturated at the intakes obtained in this study. Protein intolerance was only encountered in one patient. Available evidence indicates that the requirement for achieving N balance is increased in these patients but protein retention is highly efficient with increased intake. Protein retention is dependent on energy balance. Energy intake was calculated from food tables and total energy expenditure was calculated by the factorial method. A validation study was performed in a subgroup of patients. The energy contents of food sampled by the duplicate portion technique, and of urine and faeces were measured by bomb calorimetry. Resting energy expenditure (REE) was measured by indirect calorimetry before and at the end of the study, and O2 uptake during bicycle exercise was measured before and at the end of the study. The measured intake of metabolizable energy was on average 13% lower than the value given in food tables. Calculated energy expenditure was not changed by the validation study.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: High volume plasmapheresis has previously been found to improve neurological statuses in patients with fulminant hepatic failure. We investigated the relationship between the neurological status and cerebral blood flow velocity (Vmean) during high volume plasmapheresis in 18 consecutive patients (ten females and eight males) with fulminant hepatic failure, with a mean age of 43 (range 9 to 57) years. The mean arterial pressure (MAP) and intracranial pressure (ICP) were also recorded. A total of 16% of body weight was exchanged with fresh frozen plasma per day. Thirty-six plasma exchanges wer performed with a median of 2 (range 1 to 8) per patient. Eleven of the patients survived (61%), nine after liver transplantation. Following the first high volume plasmapheresis, the coma score improved from 6 (1-8) to 2 (0-8) (p < 0.05), Vmean increased from 40 (14-152) to 62 (16-186) cm s-1 (p < 0.05), and MAP from 72 (35-118) to 94 (47-138) mmHg (p < 0.05). The intracranial pressure (ICP) was monitored and remained unchanged in nine patients whereas the cerebral perfusion pressure (MAP minus ICP) increased in the surviving group from 55 (40-74) to 80 (50-91) mmHg (p = 0.07) in contrast to no changes in the non survival group. In conclusion this study suggests that the neurological status, may improve during high volume plasmapheresis as MAP and Vmean increase the cerebral oxygen delivery.

Abstract: The present study examined whether different proteins have different effects on whole-body protein turnover in adult rats. The rats were either starved, given a protein-free but energy-sufficient diet (1 MJ/kg body weight (BW) per d) or a diet containing intact casein, hydrolysed casein, or hydrolysed soya-bean protein at a level of 9.1 g/kg BW per d. The diets, which were isoenergetic with the same carbohydrate: fat ratio, were given as a continuous intragastric infusion for at least 4 d. During the last 19 h 15N-glycine (a primed continuous infusion) was given intragastrically and 15N was recovered from urinary ammonia and urea during isotope steady state for measurement of protein synthesis and protein degradation. Compared with starvation the protein-free diet decreased N excretion by 75%, probably by increasing the rate of reutilization of amino acids from endogenous proteins for protein synthesis. The protein diets produced a positive N balance which was independent of the protein source. Intact and hydrolysed casein increased protein synthesis 2.6- and 2.0-fold respectively, compared with the protein-free diet. Protein degradation increased 1.4- and 1.2-fold respectively. Hydrolysed soya-bean protein did not increase protein synthesis but decreased protein degradation by 35% compared with the protein-free diet. Compared with the hydrolysed soya-bean protein, intact casein resulted in 2.2- and 2.8-fold higher rates of protein synthesis and degradation respectively. These results are not easily explained by known sources of misinterpretation associated with the 15N-glycine method. Hydrolysed casein and hydrolysed soya-bean protein produced similar concentrations of insulin-like growth factor-1, insulin, glucagon, and corticosterone. The difference in amino acid composition between the dietary proteins was reflected in plasma amino acid composition and this is suggested to be responsible for the different effect on protein turnover. Preliminary results from this study have previously been published in abstract form (Nielsen et al. 1991).

Abstract: The aim of this work was to compare and validate seven different methods for estimating changes in fat free mass, in patients suffering from rheumatoid arthritis. Measurements were made of fat and fat free mass before and after 12 weeks on an energy restricted, protein rich diet and physical training. The subjects were sixteen female and three male overweight out-patients (mean body mass index at baseline: 30 kg/m2) suffering from rheumatoid arthritis, according to the criteria of the American Rheumatism Association. Fat free mass was estimated by eight different body composition methods (a four-compartment model, total body water, total body potassium, impedance, near infrared interactance, creatinine excretion, body mass index and skinfold measurements). Mean weight loss was 2.7 kg fat and 1.7 kg fat free mass. There was no difference between measurements of mean change in fat free mass by the four-compartment model and the other methods, except for the creatinine method (P = 0.03). Compared to the four-compartment method, the total body water method gave the most accurate estimate of individual fat free mass changes (residual Mean Square: 0.4 kg), second to this method, the impedance method, seemed most valid (residual Mean Square: 0.8 kg). Accuracies of the other methods were lower (residual Mean Square between 4.2 and 8.2 kg [corrected]). Of eight methods for estimating changes in FFM, the TBW method gave the most accurate estimate of individual FFM changes, compared to a four-compartment model used as reference.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: Reactive free oxygen radicals are formed in the reactions involved in normal cell metabolism. This formation is closely regulated e.g. by dietary antioxidants. Present knowledge suggests that an imbalance, with surplus of free radicals, can play a role in the pathogenesis of certain types of cancer, atherosclerosis, and cataract. A number of epidemiological studies have demonstrated a reduced risk of developing these diseases in persons who consume a diet with a high content of vegetables and fruit, which contains large quantities of the antioxidants: beta-carotene, vitamins C and E. Intervention studies, using supplements of these antioxidants, have so far not been able to show a beneficial effect. The apparently protective effect of fruit and vegetables may be due to other active ingredients. In Denmark the average intake of vegetables and fruit is low, and it is estimated that an increased consumption of these foods could reduce the occurrence of certain cancer types and atherosclerosis. In contrast, there is no evidence that antioxidant supplements would provide protection against disease, and their safety remains to be established.

Abstract: Emergency liver transplantation is the treatment of choice in acute liver failure without signs of spontaneous regeneration. However, many patients rapidly contract irreversible neurological complications before transplantation can be performed. We used high-volume plasmapheresis to increase the time span to obtain a donor liver. Four patients with acute liver failure of unknown cause and a galactose elimination capacity indicative of a virtually extinct liver function were assigned maximum priority for liver transplantation. Plasmapheresis were performed daily until transplantation. Each time 8-10 liters of patient plasma were replaced with an equal volume of fresh donor plasma. There were no major complications. None of the patients developed irreversible neurological complications for 48-144 h at which time liver transplantation was performed. High volume plasmapheresis increases the time to obtain a donor liver for emergency liver transplantation and optimizes the condition for the surgical procedure.

Abstract: Malnutrition is common among patients with cirrhosis of the liver. During the last seven years a total of eight randomized studies concerning the effect of nutritional therapy on the clinical course of these patients have been published. In five of these trials nutritional therapy had an effect on the clinical course (reduced mortality, lessening of ascites and encephalopathy) and in the last three trials only effects on clinical chemistry variables related to liver function could be demonstrated. Overall one-month mortality decreased from 30% in the control groups to 14% in the treated groups, when all the trials were added together (total of 320 patients). Patients with liver cirrhosis have an increased requirement for protein to achieve nitrogen balance. Prescribing diets with restricted protein is no longer warranted in these patients, since protein intolerance is actually uncommon. In patients intolerant of protein, substitution of conventional protein with branched chain amino acids can be effective.

Abstract: Nutritional assessment and adequacy of spontaneous dietary intake was evaluated in thirty-seven clinically stable hospitalized patients with alcoholic liver cirrhosis. About two-thirds of the patients had ascites or oedema, or both, and, therefore, body weight could not be used for assessment of nutritional status. Lean body mass (LBM; measured by three consecutive 24 h creatinine excretions) was 62 (range 40-95)% of reference values, mid-arm-muscle area (MAMA) was 70 (range 43-115)% and triceps skinfold (TSF) was 45 (range 20-113)% of reference values (all median values). In patients without ascites or oedema, or both, there was a rectilinear correlation between body weight and LBM and between body weight and MAMA (r 0.93 and 0.85 respectively). In patients with ascites or oedema, or both, the correlation between body weight and LBM was poor as could be expected. We suggest that LBM is a useful measure of nutritional status when body weight is unreliable because of ascites or oedema, or both. Energy balance for the group was calculated from energy intake recorded by a 24 h dietary recall and energy expenditure calculated by the factorial method. Median intake was 102 (range 34-176)% of expenditure. N loss was calculated from the average of three 24 h urea excretions. Protein intake was calculated from the 24 h dietary recall. The N balance was positive in the patients as a group (median intake was 120 (range 26-183)% of output). The most malnourished patients tended to have the most positive N balance which was due to a significantly lower N excretion. The protein requirement for N balance was 0.83 (SE 0.05) g/kg per d and only at an intake above 1.20 g/kg per d were all patients in positive N balance. The median intakes of thiamin, folacin, vitamin D, vitamin E, Mg, and Zn were judged to be insufficient. It is concluded that impaired nutritional status is common among patients with liver cirrhosis, even in a stable clinical condition. It is suggested that nutritional status in these patients is evaluated by dietary recalls, in combination with measurement of body weight in patients without ascites or oedema, or both, or in combination with determination of LBM by three 24 h creatinine excretions in patients with ascites or oedema, or both. Criteria for selection of patients that might benefit from nutritional therapy are discussed.

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Abstract: We investigated the effect of repeated high volume plasma exchange with fresh donor plasma in 11 patients with fulminant hepatic failure, all initially in stage 3 or 4 encephalopathy. A daily exchange of a volume equal to the extracellular volume (20% of body weight) on three consecutive days was intended. We obtained an average of 2.6 exchanges each with a mean volume equal to 16% of the body weight. Five patients (46%, 95% confidence limits 17%-77%) survived, all with acetaminophen induced liver failure. Four of the 6 non-survivors showed a temporary improvement in cerebral function. Two of the patients woke up completely. The 6 non-survivors maintained a stable condition with a systolic blood pressure > 110 mm Hg for a mean of 6.9 days after initiating plasma exchange. Plasma exchange may be considered in acute liver failure in patients with residual liver function before transplantation is finally decided. In addition, plasmapheresis may be used to keep patients with definite liver failure clinically stable until a transplant can be performed.

Abstract: Calculations based on net changes and [1-14C]oleate incorporation data suggest that fatty acids are the only precursor of acetylCoA and that extensive lipolysis takes place in hepatocyte cultures incubated with 1 mM oleate in the absence or presence of ethanol. The effect of 4-methylpyrazole on fatty acid metabolism as affected by ethanol has been studied. The ethanol-induced increase in fatty acid uptake was found to be an effect of ethanol per se, whereas the decreased oxidation of fatty acids and secretion of VLDL-triacylglycerol was found to be due to ethanol metabolism.

Abstract: The application of radiolabeled fatty acids to measurements of fatty acid oxidation is discussed and a method for measuring the rate of beta-oxidation and of acetyl-CoA oxidation to CO2 is described. In hepatocytes from starved or fed rats, ethanol inhibited total beta-oxidation in the presence of 1.3 mM palmitate by 22% and 25%, respectively. If changes in the specific radioactivity of acetyl-CoA were not corrected for, the effect of ethanol would have been overestimated by 15% and underestimated by 15% in hepatocytes from fed and starved rats, respectively. In perfused liver from fed rats, inhibition by ethanol of total beta-oxidation in the presence of 1 mM palmitate was 35%. The rate of beta-oxidation in the absence of ethanol was underestimated by 65% if proper corrections were not applied. Inhibition of the tricarboxylic acid cycle by ethanol was 57% and 72% in hepatocytes from starved and fed rats, respectively. Pyrazole titration experiments demonstrated a correlation between changes in the mitochondrial NADH/NAD+ ratio and both inhibition of the tricarboxylic acid cycle and inhibition of the beta-oxidation pathway. The concentration of acetoacetyl-CoA is suggested as an additional regulatory factor of the beta-oxidation pathway. The ethanol-induced accumulation of triacylglycerol as a consequence of the inhibition of the beta-oxidation pathway is estimated to represent a 10% increase in the cellular triacylglycerol pool/hr/g of wet weight. Hence its chemical determination requires experiments of several hours duration. Primary cultures of hepatocytes have been shown to be a useful experimental system for studies of the ethanol-induced triacylglycerol accumulation.

Abstract: In a previous report it was shown that ethanol increases the rate of accumulation of triacylglycerol by 90% in hepatocytes in primary culture. This represents the first known suitable model for in vitro studies of the ethanol-induced fatty liver. The biochemical alterations causing this accumulation of triacylglycerol remain to be elucidated, however. In the present report it is shown that (1) the effect of ethanol exhibits a time lag of 6-9 hours (2) the increment in the content of triacylglycerol caused by ethanol is increased by increased concentrations of fatty acids (3) the fatty acid uptake is not affected by ethanol (4) fatty acid synthesis is inhibited 20% by ethanol (5) the contents of diacylglycerol and phospholipids are not affected by ethanol (6) addition of ethanol increases the cytosolic and mitochondrial redox levels. It is concluded that ethanol is likely to exert its effect on the accumulation of triacylglycerol by redistributing fatty acids between oxidation and triacylglycerol synthesis and/or between storage and secretion of triacylglycerol.

Abstract: Isolated rat hepatocytes were cultured in a modified HI-WO/BA medium for 16 h. In the following 24 h oleate or oleate plus ethanol was added to the medium. After this period the medium was changed again and the cultures were further incubated with [1-14C]oleate alone or with [1-14C]oleate plus ethanol for 6 h. This allowed a comparison of effects of short-term (6 h) and long-term (24 + 6 h) exposure to ethanol on fatty acid metabolism. The increased intracellular accumulation of triacylglycerol in the presence of ethanol was quantitatively accounted for by increased fatty acid uptake, by decreased fatty acid oxidation in the tricarboxylic acid cycle and by decreased VLDL (very-low-density lipoprotein)-triacylglycerol secretion. Ketone-body production was not affected. After short-term exposure the rate of accumulation of triacylglycerol was increased by 50%. This increase was accounted for by increased fatty acid uptake (44%), decreased tricarboxylic acid-cycle activity (49%) and decreased VLDL-triacylglycerol secretion (7%). After long-term exposure, the rate of accumulation of triacylglycerol was increased by 74%. This increase was accounted for by increased fatty acid uptake (34%), decreased tricarboxylic acid-cycle activity (34%) and decreased VLDL-triacylglycerol secretion (32%). The larger increase in accumulation of triacylglycerol after long-term exposure to ethanol was entirely accounted for by increased inhibition of secretion of VLDL-triacylglycerol. The biochemical mechanisms underlying the observations are discussed.

Abstract: Peroxisomes catalyze the beta-oxidation of fatty acids but their quantitative role in fatty acid catabolism in the intact hepatocyte is not yet clarified. In the present study peroxisomal beta-oxidation of [1-14C]palmitate was quantitated in hepatocytes without the use of metabolic inhibitors. It was assumed that acetyl-CoA formed by peroxisomal beta-oxidation enters the cytosolic pool of acetyl-CoA, whereas that from mitochondrial beta-oxidation enters the mitochondrial pool. The labeling of the two acetyl-CoA pools was assessed by measuring the incorporation of radioactivity into cholesterol (from cytosolic acetyl-CoA) and CO2 (from mitochondrial acetyl-CoA). The system was calibrated with [1-14C]acetate and [1-14C]butyrate because butyrate undergoes beta-oxidation only in mitochondria, whereas acetate forms acetyl-CoA primarily in the cytosol. The labeling ratio, [( 14C]cholesterol X 100)/[( 14C]cholesterol + [14C]CO2), reflects the site of formation of acetyl-CoA. This ratio was 0.51 for butyrate, 1.39 for acetate and 0.79 for palmitate. The difference between palmitate and butyrate was statistically significant (P less than 0.02). This indicates that not all of the palmitate was oxidized in mitochondria. By linear interpolation it was estimated that approximately 32% of the [1-14C]palmitate oxidation began in peroxisomes.

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Abstract: Improved methods for the determination of the rate of fatty acid oxidation and lipolysis are presented and evaluated. Hepatocytes from fed rats were incubated with 1.3 mM palmitate. The rate of oxidation of exogenous fatty acids was determined with [1-14C]palmitate. The rate of oxidation of endogenous fatty acids was determined either as the difference between total fatty acid oxidation and oxidation of exogenous fatty acids, or as the oxidation of intracellular lipids, prelabelled with 14C. The two methods agreed completely, indicating that the only endogenous source of acetylCoA was fatty acids. The rate of oxidation of exogenous and endogenous fatty acids was estimated to be 858 and 284 nmol C2-units/min 10(8) cells, respectively, and the rate of lipolysis to be 1640 nmol C2-units/min 10(8) cells. Ethanol caused a 17% and 70% inhibition of the oxidation of exogenous and endogenous fatty acids, respectively. Lipolysis was inhibited approximately 10% by ethanol. Noradrenaline was without effect on the oxidation of exogenous and endogenous fatty acids and on lipolysis. 3',5'-Cyclic AMP enhanced the oxidation of exogenous and endogenous fatty acids by 25% and 31%, respectively, and the rate of lipolysis by 38%, suggesting the presence in hepatocytes of a cAMP sensitive lipase.

Abstract: Isolated hepatocytes from female rats were cultured in HI-WO/BA medium for 6 days. To the medium was added oleate, ethanol, dexamethasone and insulin. With oleate To alone, triacylglycerol accumulated; ethanol augmented the accumulation by 90%. To the best of our knowledge, this is the first demonstration that ethanol in vitro increases the content of triacylglycerol in liver cells. Further addition of dexamethasone or insulin did not alter the accumulation of triacylglycerol, indicating that these hormones did not play permissive roles for the effect of ethanol in the present system. Dexamethasone and insulin, in the absence of ethanol, increased the accumulation of triacylglycerol by 30% and 50% respectively. The concentration of glycerol 3-phosphate was increased in the presence of ethanol; however, with time the concentration of glycerol 3-phosphate declined almost to control values, while the accumulation of triacylglycerol continued linearly; this suggests that the effect of ethanol was not mediated via fluctuations in the concentration of glycerol 3-phosphate. These results are discussed in relation to earlier investigations in vivo and in vitro.

Abstract: Cellular protein and DNA content were determined by Feulgen--Naphthol Yellow S cytophotometry on isolated liver cells from rats fed ethanol for 2--6 months. It was found that parenchymal liver cells after ethanol feeding contained 13% more protein than cells of the same ploidy class from controls; that the average parenchymal cell in ethanol-fed rats contained 16% more protein than in controls due to the increased occurrence of polyploid cells; that the protein accumulation develops over 2 months, does not progress thereafter and disappears after a few days of reduced ethanol intake; that the tendency to form polyploid cells is accentuated during liver regeneration. It is suggested that the effect of alcohol on microtubular function, which is regarded as the cause of the protein accumulation, may also bring about increased polyploidization.

Abstract: A procedure for fractionation of hepatocytes according to density is presented. Hepatocytes were prepared from rats fed an ethanol-containing liquid diet, a liquid diet without ethanol, or a chow diet. The hepatocytes were fractionated in a Metrizamide density gradient and the cell fractions obtained were characterized with respect to protein synthesis, fatty acid oxidation, and esterification and ATP content. From ethanol-fed rats, two fractions of hepatocytes were obtained, one with a density of approximately 1.04 gm. per ml. and one with a density of ca. 1.08 gm. per ml. Cells from the lighter fraction contained 3 times more triacylglycerol than cells from the heavier fraction. Fifty per cent of the cells from the lighter fraction contained large (greater than 5 micron) lipid droplets as compared to 6% in the heavier fraction. The average yield from a 170-gm. rat of lipid-rich and lipid-poor cells was about 65 x 10(6) and 170 x 10(6) cells, respectively. Electron micrographs of the liver before perfusion and of the isolated and washed cell fraction revealed intact ultrastructure. Fractionation of hepatocyte suspensions from rats fed a high fat liquid diet without ethanol or a chow diet normally yielded two cell fractions with densities of ca. 1.08 and 1.10 gm. per ml. and 1.10 and 1.12 gm. per ml., respectively. The metabolic capacity of the cell fractions was unaltered by the fractionation procedure as judged by the ATP content, the rate of palmitate oxidation and esterification, and the rate of protein synthesis.

Abstract: 1. In the preceding paper [Kondrup (1979) Biochem. J.184, 63-71] the separation of two major fractions of hepatic triacylglycerol was described. One fraction contained triacylglycerol from the endoplasmic reticulum and from the Golgi apparatus. The other fraction contained triacylglycerol from the cytoplasmic lipid droplets. In the present paper possible precursor-product relationships between the two fractions were investigated by means of computer models. 2. The fatty acids present in di- and tri-acylglycerol in the fractions isolated in the time studies were analysed by gas chromatography. From this analysis the relative specific radioactivities, and contents, of palmitate in acylglycerols in the two fractions at the various time points were calculated. 3. A computer was used to predict relative specific radioactivities of pools in defined models of hepatic triacylglycerol metabolism. The acceptability of the models was evaluated by comparing predicted with measured relative specific radioactivities. 4. It is suggested that triacylglycerol in cytoplasmic lipid droplets does not originate (a) directly from triacylglycerol in the endoplasmic reticulum, (b) from a sub-pool of it or (c) directly from non-esterified fatty acids entering the cell. Rather, it is formed from diacylglycerol (and acyl-CoA) in the endoplasmic reticulum. Diacylglycerol, on the other hand, is furnished in part by hydrolysis of triacylglycerol in the endoplasmic reticulum. 5. This suggestion is discussed in relation to previous models of hepatic fatty acid metabolism.

Abstract: 1. The metabolism of [1-14C]palmitate in rat liver was studied in a single-pass perfusion system at concentrations of 0.2 or 1 mM. 2. After the perfusion the liver was homogenized and the floating fat was isolated. The incorporation of [1-14C]palmitate into triacylglycerol in this pool increased 9-fold when the palmitate concentration in the medium was increased from 0.2 to 1 mM. In time studies with 1 mM-[1-14C]palmitate 75% of the total accumulation of triacylglycerol occurred in this pool. Our results support the concept that the floating-fat fraction contains the storage pool of triacylglycerol, i.e. the cytoplasmic lipid droplets. 3. In a particulate preparation consisting mainly of mitochondria and microsomal fraction the incorporation of [1-14C]palmitate into triacylglycerol was proportional to the fatty acid concentration. Triacylglycerol in the perfusate medium and in the particulate fraction was in isotopic equilibrium, which indicates that the particulate fraction contained the precursor pool for secreted triacylglycerol, i.e. the pool in endoplasmic reticulum and Golgi apparatus. 4. The oxidation to labelled water-soluble products and to CO2 was increased 14-fold by the 5-fold increase in palmitate concentration.

Abstract: 1. The effect of ethanol on the metabolism of [1-(14)C]palmitate in rat liver was investigated in a single-pass perfusion system at concentrations of 10mm- or 80mm-ethanol and 0.2mm- or 1mm-palmitate. 2. After the perfusion the hepatic lipid was isolated in subcellular fractions. The two major fractions contained triacylglycerol from cytoplasmic lipid droplets and from endoplasmic reticulum plus Golgi apparatus respectively. 3. In experiments with 0.2mm-palmitate perfusion with 10mm- or 80mm-ethanol did not measurably increase the esterification, and the oxidation was markedly decreased and the fatty acid uptake was not affected. 4. Perfusion with ethanol, at 1mm-palmitate, increased the fatty acid uptake, increased esterification and decreased oxidation. The effects of 10mm- and 80mm-ethanol were similar. The incorporation of [1-(14)C]palmitate into triacylglycerol in cytoplasmic lipid droplets was not affected statistically significantly by ethanol. Ethanol increased the incorporation of [1-(14)C]palmitate into di- and tri-acylglycerol in the membranous fraction. Estimated chemically, the contents of di- and tri-acylglycerol were only slightly affected by ethanol. These results suggest that the effect of ethanol was to increase the turnover of fatty acids in triacylglycerol rather than to increase its accumulation. 5. The results indicate that an increased concentration of fatty acids is more important for the formation of acute fatty liver in fed rats than are the direct effects of ethanol on hepatic fatty acid metabolism.

Abstract: 1. Rats were treated for 4 weeks with liquid diets that contained, on the basis of energy content, 35% fat, 18% protein and 47% carbohydrate (high-fat diet) or 35% fat, 18% protein, 11% carbohydrate and 36% ethanol (high-fat/ethanol diet). 2. The livers were perfused with 1mm-[1-(14)C]palmitate and with 0, 10mm- or 80mm-ethanol. The oxidation and esterification of palmitate was measured. Two subcellular pools of triacylglycerol were separated; one contained triacylglycerol from cytoplasmic lipid droplets and the other contained triacylglycerol from the endoplasmic reticulum and Golgi apparatus. 3. In the presence of ethanol, liver from rats fed on the high-fat diet esterified about 70% of the [1-(14)C]palmitate taken up compared with 90% in liver from rats fed chow (containing 11% fat on the basis of energy content). Compared with chow diet the high-fat diet did not potentiate the effect of ethanol on storage of [1-(14)C]palmitate in hepatic triacylglycerol. The relation between the fat content of the diet and the degree of fatty liver induced by by ethanol [Lieber & DeCarli (1970) Am. J. Clin. Nutr.23, 474-478] is discussed. 4. The ethanol-containing diet increased the hepatic content of triacylglycerol 4-fold and the increase was exclusively found in the fraction suggested to contain lipid from cytoplasmic lipid droplets. The ethanol-induced fatty liver, perfused with ethanol, esterified and oxidized palmitate at rates that were quite similar to the rates found in high-fat control livers perfused without ethanol. This suggests that the fatty liver had adapted to the presence of ethanol with respect to palmitate metabolism. 5. O(2) and ethanol uptake by the livers were not affected by the ethanol-containing diet.

Abstract:

Abstract: 1. CoA, acetyl-CoA, long-chain acyl-CoA, carnitine, acetylcarnitine and long-chain acylcarnitine were measured in rat liver under various conditions. 2. Starvation caused an increase in the contents of these intermediates, except that of carnitine. 3. A single dose of ethanol had no effect on CoA content, whereas those of acetyl-CoA, acetylcarnitine and carnitine were increased and those of long-chain acyl-CoA and acylcarnitine were decreased. 4. Four weeks' adaptation to ethanol consumption did not change the effect of ethanol administration on these metabolites. 5. It is suggested that ethanol directly increases hepatic fatty acid synthesis and esterification. It is also suggested that this change is reversible and limited to the period of ethanol oxidation. 6. It is demonstrated that ethanol-induced triglyceride accumulation is not related to carnitine deficiency.