G.R. Swart

Minimum protein requirements in liver cirrhosis determined by nitrogen balance measurements at three levels of protein intake.

Nitrogen balance at three levels of protein intake was measured in eight patients with cirrhosis of the liver; moreover, at each level of protein intake, the effects on nitrogen balance of branched-chain amino-acid enriched protein and natural protein were compared. From these nitrogen balance data, minimum protein requirements were calculated by linear regression analysis. The patients were in a negative nitrogen balance on a 40 g protein diet (-0.75 +/- 0.15 gN.), and in positive nitrogen balance on 60 g (+1.23 +/- 0.22 gN.) or 80 g of protein per day (+2.77 +/- 0.20 g N.). Their mean minimum protein requirement (48 +/- 5 g of protein/day or 0.75 g/kg/day) is higher than expected in healthy people; the safe level of protein intake (mean + 2 sd) is 58 g per day or 1.2 g/kg/day. Nitrogen balances and protein requirements were not different on branched-chain amino-acid enriched diets. The physical condition of the patients improved when they came into positive nitrogen balance; the higher rates of protein intake were well tolerated without onset of encephalopathy. We conclude that protein requirements are elevated in cirrhosis of the liver; diets supplying less than 60 g of protein per day should not be prescribed in long term treatment of cirrhotic patients.

Nocturnal oral glucose supplementation. The Effects on protein metabolism in cirrhotic patients and in healthy controls

Nocturnal glucose administration might prevent gluconeogenesis and concomitant protein loss due to hepatic glycogen depletion. In this study the effects of nocturnal oral glucose supplements on nitrogen metabolism were investigated in 8 cirrhotic patients and in 8 healthy controls. During the night, either polymeric glucose was given or water as placebo. In the patients with cirrhosis on placebo, nitrogen balance was not different from controls: -63 +/- 8 vs. -55 +/- 4 mg N/kg b.wt./9 h (mean +/- SEM). Cirrhotic patients had increased nocturnal protein turnover rates (measured with 15N-glycine) and increased early morning levels of free fatty acids (FFA), lactate, insulin, glucagon and growth hormone. After glucose, nitrogen balance improved by 36% in the cirrhotic group, with a decrease in protein turnover rates and a decrease in plasma levels of beta-hydroxybutyrate, urea and glucagon. In the controls, glucose had no effects on nitrogen balance, on protein turnover or on the hormone levels, except for reduced FFA and ketone body levels. These data show that nocturnal calorie supplements improve nitrogen balance during the night in cirrhotic patients but not in healthy controls. Long interprandial intervals should be avoided in cirrhotic patients.

Body Composition in Patients With Acquired Immunodeficiency Syndrome: A Validation Study of Bioelectric Impedance Analysis

The objective of this validation study was to explore bioelectric impedance analysis (BIA) as a way to assess nutritional status and body composition. The study was done in the outpatient department of the AIDS unit at University Hospital Dijkzigt, Rotterdam, The Netherlands. Eleven clinically stable patients with AIDS were studied. Total body water, body fat, lean body mass, and body cell mass were measured and calculated with multiple dilution techniques and BIA. With linear regression analysis, a strong correlation was found between total body water and lean body mass derived from BIA and multiple dilution techniques (r2 = .96 and .98, respectively), and slightly weaker correlation was found for body cell mass and body fat (r2 = .88 and .76, respectively). These results suggest that BIA is a suitable method for the assessment of body cell mass in HIV-infected patients without opportunistic infections. The technique is safe, noninvasive, fast, and inexpensive.

Evaluation Studies of the 13C-Mixed Triglyceride Breath Test in Healthy Controls and Adult Cystic Fibrosis Patients with Exocrine Pancreatic Insufficiency

The 13C-mixed triglyceride (13C-MTG) breath test (BT) is a safe and noninvasive method to measure exocrine pancreatic function. We examined the reproducibility of the 13C-MTG BT in a group of 17 healthy controls and 8 adult patients with cystic fibrosis (CF). In controls no statistically significant difference in percentage dose recovered (PDR) was found between the first and the second result of repeated tests: the mean values were 35.5 +/- 5.5 vs. 32.3 +/- 7.4 PDR (n = 17). Also in the group of CF patients (n = 8) no significant difference between duplicate tests was found: mean values 17.5 +/- 7.5 and 17.5 +/- 7.8 PDR, respectively. The coefficient of repeatability is 8 PDR for the controls and CF patients together. Two factors might influence the outcome of the test. First, individually measured CO2 excretion instead of the usually assumed 9 mmol/h/kg CO2 production might alter the result of the 13CO2-MTG BT. Therefore CO2 production was measured by indirect calorimetry in 12 healthy controls and 13 CF patients. Measured CO2 excretion was not significantly different between healthy controls and CF patients. Secondly, exercise might influence BT results due to its separate effects on both CO2 production and excretion. The influence of physical exercise at a level of 25 or 50 W was studied on a bicycle ergometer in 4 healthy controls during the last 5 min of each 30-min sampling period. Exercise gave lower test results, on average 85% of the PDR value at rest. Incidently, it was observed in 1 patient that use of 13C-enriched food during the day preceding the test caused inappropriately low test results in the 13C-MTG BT. The 13C-MTG BT is a test with a fair but less than desirable reproducibility. Test conditions should be standardized to eliminate confounding influences. Exercise should be limited or strictly defined. Diet on the day preceding the test should not contain naturally 13C-enriched food. There is no need to measure individual CO2 production.

Small bowel wall function in patients with advanced liver cirrhosis and portal hypertension studies on permeability and luminal bacterial overgrowth

Objective: Changes in small bowel function could contribute to the complications of cirrhosis including malnutrition, infection and encephalopathy. To evaluate small bowel function, we studied intestinal permeability and luminal bacterial overgrowth in patients with cirrhosis of the liver and portal hypertension. Design: The 14C-glycocholic acid breath test was used to evaluate the presence of bacterial overgrowth and urine excretion of orally ingested 51Cr-EDTA was used to measure intestinal permeability. Intestinal clearance of α-1-antitrypsin and faecal blood loss were also measured. Setting: Gastroenterology and hepatology unit of a university hospital. Patients: A total of 18 patients were studied. Results: No evidence of small intestinal bacterial overgrowth or increased permeability of the small bowel was found. However, 28% of the patients had increased faecal blood loss. Conclusions: Although the number of patients investigated was small, our data suggest that small bowel function is maintained to a large extent in patients with advanced liver cirrhosis and portal hypertension.

13 C Breath Tests in Gastroenterological Practice

Breath tests (BTs) are used in gastroenterological practice to study (patho)physiological and metabolic processes in an indirect way. In these tests the appearance in breath of a metabolite of a specific test substance is studied. The assumption underlying each BT is that one step-the process of interest-in the absorption and metabolism of the tracer is rate-limiting. Both hydrogen gas excretion and carbon dioxide appearance in breath can be studied. When a carbon-labelled test substance is used, the stable isotope 13 C is preferred to the radioactive isotope 14 C. Measurements of 13 C in expired air are performed by mass spectrometry. Because of the indirect nature of BTs, involving a sequence of reactions and metabolic pools, they usually supply semiquantitative data. The tests are nevertheless useful because they often replace invasive techniques with a simple procedure that is safe because there is no radioactivity involved. BTs have been used to measure gastric emptying, the presence of Helicobacter ...

Peritoneal protein losses and cytokine generation in automated peritoneal dialysis with combined amino acids and glucose solutions.

Objectives. Protein-energy malnutrition as a consequence of deficient protein intake frequently occurs in peritoneal dialysis (PD) patients. Previously, we showed that peritoneal dialysate containing a mixture of amino acids (AA) and glucose has anabolic effects. However AA-dialysate has been reported to increase intraperitoneal protein and AA losses and the release of proinflammatory cytokines (interleukine-6 (IL-6) and tumor necrosis factor alpha (TNFα)). We investigated the effect of AA plus glucose (AAG) solutions on peritoneal protein losses and cytokine generation. Methods. In 6 patients on standard automated peritoneal dialysis (APD) 12 APD sessions of 6 cycles each were performed during the night using dialysate containing 1.1% AA plus glucose or glucose alone as control. Protein losses and TNFα and IL-6 concentrations were measured in dialysates separately collected from nightly cycling and daytime dwell. Results. The 24 hour-protein losses with AAG (median 6.7 g, range 4.7–9.4 g) were similar to control dialysate (median 6.0 g, range 4.2–9.2 g). Daytime dialysate IL-6 levels were higher after nightly AAG dialysis than after control dialysis (142 pg/ml and 82 pg/ml, respectively, P<.05). TNFα concentrations were very low. Conclusion. Nightly APD with amino acids containing dialysate was associated with an increase in peritoneal IL-6 generation during the day. The addition of AA to standard glucose dialysis solutions did not induce a significant increase of peritoneal protein losses.

Influence of the 13C-enrichment of the habitual diet on a 13CO2 breath test used as an index of liver glycogen oxidation: A validation study in Western Europe and Africa

A diet containing naturally 13C-enriched carbohydrate combined with a 13CO2 breath-test analysis can be used to monitor liver glycogen oxidation in persons used to a diet low in 13C, e.g., the Western European diet. In this study, we evaluated this test principle further by changing the way we label the glycogen pool. The 13C enrichment of exhaled CO2 was studied in two groups, one in Europe and one in Africa. The European group (n = 12) was accustomed to a diet low in 13C, and they went on a 13C-enriched study diet to identify liver glycogen. The African group (n = 6) was accustomed to a diet naturally high in 13C, and they went on a diet low in 13C. The basal 13C abundance in exhaled CO2 was higher in the African group (1.0879 At%; atmospheric 1.1 atom percent) than in the European group (1.0821 At%). During the study period, the parameters for liver glycogen oxidation--the 13CO2 enrichment plateau, the plateau duration, and the return to baseline time--did not differ between groups. The abundance of 13CO2 in exhaled CO2 over time in the two groups was similar but inverse. This study confirms the use of a 13CO2 breath test to monitor liver glycogen oxidation and demonstrates how to use such a test in persons accustomed to a diet high in 13C.

The 13CO2 breath test for liver glycogen oxidation after 3-day labeling of the liver with a naturally 13C-enriched diet

OBJECTIVE When naturally (13)C-enriched carbohydrate is used to label hepatic glycogen, (13)C-liver glycogen oxidation can be monitored subsequently by measuring the (13)C enrichment of breath CO(2) during a sedentary fast. In our previous breath test studies, we used a 1-d labeling protocol to enrich liver glycogen. Others found that after 3 d of labeling the liver glycogen (13)C enrichment is identical to the dietary carbohydrate (13)C enrichment. METHODS We compared a diet protocol in which naturally (13)C-enriched carbohydrate was given for 3 d before the breath test with our previously applied 1-d labeling design. The (13)CO(2) breath test was combined with indirect calorimetry. The results were compared with those from our previous studies. In addition, we compared liver glycogen oxidation rates with those from our present technique and different techniques as used in other published studies. RESULTS Six healthy volunteers were included in this study. The (13)C enrichment of breath CO(2) at plateau excretion level did not differ after 1 or 3 d on a labeling diet. However, the end of plateau time tended to be later after the 3-d diet, 14.3 h versus 12.5 to 13.5 h postprandially in the 1-d labeling studies. Also, the return to baseline time was later in the 3-d study, at 25.8 h versus 19.0 to 23.2 h postprandially after 1 d of labeling. The liver glycogen oxidation rate was similar in both techniques until 17 h postprandially. After this time the 3-d labeling protocol showed a higher level of liver glycogen oxidation. CONCLUSION The results indicated that the labeling of liver glycogen is slightly less complete after 1 d on a (13)C-enriched diet as compared with 3-d labeling. Our (13)C breath test results compared rather well with studies from the literature using the (13)C-NMR technique, the D(2)O technique, or the (13)CO(2) breath method to measure liver glycogen oxidation.