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BACKGROUND: Patients suffering from post-polio syndrome still contribute significantly to the number of patients with chronic respiratory failure requiring home mechanical ventilation (HMV). Many of these patients are treated either with invasive (tracheostomy) or non-invasive (nasal mask) controlled mechanical ventilation i.e. volume-controlled ventilation (VCV). In this group of patients, we have previously shown that bi-level pressure support ventilation (bi-level PSV) decreases the oxygen cost of breathing. The aim of this study was to compare the effect of bi-level PSV, with special regard to the adequacy of ventilation and the oxygen cost of breathing, during the patients' ordinary VCV and spontaneous breathing. METHODS: Eight post-polio patients on nocturnal VCV were investigated. Five of them were tracheostomized and three of them used a nasal mask. Work of breathing was analysed by assessing differences in oxygen consumption (VO2) using indirect calorimetry. Blood gases were obtained regularly to assess adequacy of ventilation. RESULTS: Bi-level PSV decreases the oxygen cost of breathing in post-polio patients with respiratory failure without decreasing ventilation efficiency. Furthermore, PaCO2 decreased significantly using this mode of ventilation (P < 0.05). CONCLUSION: In this study, it was shown that bi-level PSV reduces the oxygen cost of breathing and gave a significant decrease in PaCO2 in PPS patients. These data suggest that bi-level PSV ventilation maintains adequate ventilation in patients who suffer from post-polio syndrome with respiratory failure.

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BACKGROUND: Today, patients with chronic respiratory failure are commonly treated with non-invasive bi-level positive airway pressure ventilation, supporting spontaneous breathing. However, in conformity with previous clinical routine, many post-polio patients with chronic respiratory failure are still treated with invasive (i.e. via a tracheostomy) controlled mechanical ventilation (CMV). The aim of the study was to investigate the effect of invasive bi-level positive airway pressure ventilation on the work of breathing compared with that during the patients' ordinary CMV and spontaneous breathing without mechanical support. METHODS: Nine post-polio patients on invasive (tracheostomy) nocturnal CMV were investigated. Work of breathing was analysed by assessing differences in oxygen consumption (VO2) using indirect calorimetry. Hereby, the oxygen cost of breathing during the various ventilatory modes could be estimated and related to one another. Data on energy expenditure were also obtained. RESULTS: The oxygen cost of breathing decreased by approximately 15% during bi-level positive airway pressure ventilation compared with CMV and spontaneous breathing. There was no difference between predicted (Harris-Benedict equation) and measured energy expenditure. CONCLUSION: Invasive bi-level positive airway pressure ventilation reduces the oxygen cost of breathing in long-standing tracheostomized post-polio patients, compared with CMV. Furthermore, the Harris-Benedict equation provides a reasonable prediction of energy expenditure in this group of patients.

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BACKGROUND & AIMS: Progressive muscle wasting is a characteristic feature of patients treated at the intensive care unit (ICU). As a consequence, endogenous glutamine production by skeletal muscle may be compromised. We investigated the time pattern of the glutamine and glutamate net balance across the leg in long-stay ICU patients. METHODS: Critically ill patients with multiple organ failure that were expected to stay in the ICU for more than 3 days were included in a longitudinal study. Possible changes in amino acid net balance over the leg muscle were investigated overtime. The patients (n=20) were studied descriptively every third or fourth day, on a total of 2-7 occasions. MAIN RESULTS: The glutamine net release from leg muscles did not change significantly during the initial 2 weeks of ICU stay and was not related to the plasma concentration of glutamine. The net uptake of glutamate across the leg muscles was unaltered during this time period, but it was found to correlate statistically with both the arterial glutamate concentration and the glutamine net release. A continuous net release of phenylalanine indicated a progressive net loss of muscle protein in these patients. CONCLUSION: The net release of glutamine from skeletal muscle does not decrease in stabilized critically ill patients with multiple organ failure over the initial 2 weeks of ICU stay, despite progressive muscle wasting.

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Advanced simulation within medicine and health care is a rapidly growing field. Simulator based training can be applied in minimal invasive surgery, in endoscopic procedures as well as in anaesthesia and critical care management. At Huddinge University Hospital a center for advanced simulation of both endoscopic surgery and anaesthesia/critical care management is currently being set up. The objective is to focus on improved medical and health care training and thus improving patient safety by reducing medical errors.

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OBJECTIVE: To study the effect of growth hormone (GH) on albumin synthesis in critically ill patients. DESIGN: Prospective randomized controlled study. SETTING: Two intensive care units, university hospital and county hospital, respectively. PATIENTS: Twenty-two critically ill patients in the intensive care unit. INTERVENTIONS: Albumin synthesis was measured twice in each patient, with a 5-day interval. The patients in the control group (n = 11) received standard intensive care unit (ICU) treatment between measurements, whereas those in the GH group (n = 11) also received 0.3 U/kg daily of human recombinant GH. MEASUREMENTS AND RESULTS: Albumin synthesis was measured by labeling with L-[2H5]phenylalanine. In the control group, the fractional synthesis rate (FSR) of albumin was 16.3+/-4.1%/day (mean and SD) in the first measurement and 15.7+/-4.2%/day 5 days later (NS), whereas in the GH group the corresponding values were 17.0+/-4.7%/day and 16.7+/-5.5%/day (NS). The calculated absolute synthesis rates of albumin, based on FSR and intravascular albumin mass, also showed no effect of GH. CONCLUSION: Albumin synthesis rates were consistently higher in the two groups of critically ill patients than previously reported values in healthy subjects. However, GH treatment for 5 days neither stimulated nor inhibited albumin synthesis rates in these critically ill patients.

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BACKGROUND AND AIMS: In this study the effects of acute (5 h) and short-term (5 days) GH treatment on albumin synthesis rates in man were investigated and related to changes in the availability of hepatic albumin mRNA. METHODS: 30 patients undergoing elective laparoscopic cholecystectomy were randomized into controls (n=10) or GH-treatment (12 U/dose) for 5 h or 5 days (n=10 in each group). Albumin mRNA levels (in liver biopsy specimens) were measured employing a quantitative polymerase chain reaction assay developed specifically for this purpose, whereas albumin synthesis was measured using [(2)H(5)]phenylalanine. RESULTS: The fractional synthesis rate of albumin was 6.0+/-0.9 %/day in the control group and 8.0+/-1.8 %/day and 8.3+/-1.7 %/day in the GH-treated groups, respectively (P<0.05 vs controls in both cases). The corresponding values for the concentration of albumin mRNA were 2.6+/-1.1 ng/microg total RNA, 2.9+/-0.8 ng/microg total RNA (NS) and 4.7+/-1.8 ng/microg total RNA in the "GH 5" group (P<0.01 vs controls). The changes in albumin synthesis were only partly explained by the differences in hepatic albumin mRNA levels (r=0.5, P<0.01). CONCLUSION: These results suggest that GH may induce a quick, gene expression-independent increase in albumin synthesis, which is sustained by a later-occurring increase in albumin gene expression.

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Previous studies have indicated that laparoscopic surgery is associated with a decline in liver protein synthesis. In this study, the fractional synthesis rate (FSR) of total liver protein and albumin was measured in patients undergoing elective laparoscopic cholecystectomy at different times after commencing the procedure (n = 8 + 8). Liver biopsy specimens were taken after 15 min of surgery in an "early" group and after 49 min of surgery in a "late" group. The liver FSR was higher in the early group (24.1 +/- 4.7%/day) compared with the late group (19.0 +/- 2.8%/day, P < 0.02). The fractional and absolute synthesis rates of albumin were similar in the two groups, 6.4 +/- 1.5 vs. 6.5 +/- 1.0%/day and 97 +/- 19 vs. 96 +/- 18 mg. kg(-1). day(-1) for the early and late groups, respectively. It is concluded that laparoscopic surgery was accompanied by a decrease in total liver protein synthesis rate, which developed rapidly during surgery. In contrast, no change in the synthesis rate of albumin was apparent during the course of surgery.

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This study was undertaken to elucidate the specific effects of growth hormone (GH) on liver protein metabolism in humans during surgery. Otherwise healthy patients scheduled for elective laparoscopic cholecystectomy were randomized into controls (n = 9) or pretreatment with 12 units of GH for 1 day (GH 1, n = 9) or daily for 5 days (GH 5, n = 10). The fractional synthesis rate of liver proteins, as assessed by flooding with [2H5]phenylalanine, was higher in the GH 5 group (22.0 +/- 6.9%/day, mean +/- SD, P < 0.05) than in the control (16.1 +/- 3.1%/day) and GH 1 (16.5 +/- 5.5%/day) groups. During surgery, the fraction of polyribosomes in the liver, as assessed by ribosome analysis, decreased in the control group by approximately 12% (P < 0.01) but did not decrease in the GH-treated groups. In addition, the concentrations of the essential amino acids and aspartate in the liver decreased in response to GH treatment. In conclusion, GH pretreatment decreases hepatic free amino acid concentrations and preserves liver protein synthesis during surgery.

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We investigated the acute (4-5 h) and short-term (5 days) effects of GH treatment on hepatic messenger RNA (mRNA) levels of the genes for the insulin-like growth factors (IGFs), insulin-like growth factor binding protein-1, -2, and -3 (IGFBPs), and the acid labile subunit (ALS), as well as serum levels of these proteins in humans. At the mRNA level, we observed an increase in IGF-1 transcription (+173%) following GH treatment in the acute group, which remained elevated in the short-term treatment group. IGFBP-2 mRNA decreased after short-term GH treatment, without changes in IGFBP-1 or -3 expression. The ALS transcript level increased after 5 days. In serum, we found increased levels of IGF-I and insulin, and decreased levels of IGF-II, in the short-term treatment group. IGFBP-1 decreased in both treatment groups, whereas IGFBP-2 was reduced after 5 days treatment. ALS increased in the short-term group. We observed increased IGFBP-3 serum levels after 5 days of GH treatment, likely due to increased formation of the ternary complex. Our results show that the metabolic effects by GH on the IGF axis are complex. In addition to a direct stimulation of IGF-I and ALS expression, GH inhibits IGFBP-1 serum levels and IGFBP-2 expression in an indirect manner, possibly facilitating enhanced IGF bioavailability to target tissues.

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BACKGROUND: This study was undertaken to elucidate the specific effects of short-term artificial nutrition on human liver protein metabolism. METHODS: Thirty patients undergoing elective laparoscopic cholecystectomy were studied: a control group (n = 16) and a group that received total parenteral nutrition (TPN; n = 14). The nutrition consisted of a balanced i.v. solution of nutrients (17.5 nonprotein kcal/kg body wt, 50% fat, 50% carbohydrates, and 0.1 gN/kg) that was discontinued when the investigation was finished, after a total infusion time of 8.6 +/- 1.0 hours. A liver biopsy specimen was taken as soon as possible after surgery was started, for the determination of the free hepatic amino acid concentrations. In 16 of the patients, L[2H5]phenylalanine was given by i.v. to determine the fractional synthesis rate of total liver protein in a second liver biopsy specimen taken approximately 30 minutes later. RESULTS: The fractional synthesis rate of total liver protein was 15.2% +/- 4.7%/d in the TPN group (n = 7), which was not different from that of the control group (17.7% +/- 3.8%/d, n = 9). However, the free hepatic concentrations of alanine (p < .05) and the essential amino acids increased (p < .001) in the TPN group, whereas the total hepatic amino acid concentrations were comparable between the groups. CONCLUSION: Thus short-term TPN induced specific changes of the free hepatic amino acid concentrations, whereas total liver protein synthesis remained unaffected by the nutrition.

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Although the metabolism of liver-derived plasma proteins such as albumin has been extensively studied, human hepatic protein synthesis as a whole has not been well characterized, because a reproducible model for obtaining human liver tissue has not been available. In this study, the fractional synthesis rates of total liver protein and albumin in vivo were determined simultaneously in nine subjects undergoing elective laparoscopic cholecystectomy. L-[2H5]phenylalanine (45 mg/kg body wt) was administered for 10 minutes intravenously. Blood samples were collected at regular intervals for 90 minutes and a liver biopsy specimen was taken at 35 +/- 7 minutes. The enrichments of plasma free phenylalanine, plasma albumin, and total liver protein were measured with gas chromatography mass spectrometry (GC-MS). The fractional synthesis rate (FSR) of total liver protein was 24.7 +/- 3.1 %/d (mean +/- SD), and that of albumin was 5.9 +/-1.2%/d. The amount of albumin synthesized per day (absolute synthesis rate, ASR) was 109 +/- 21 mg/kg body wt. No correlation between FSR of total liver protein and ASR of albumin was found. It is concluded that the technique of obtaining liver tissue specimens during laparoscopic surgery may serve as a human in vivo model to study total liver protein synthesis. The fractional synthesis rate of total liver proteins (stationary and exported), equals approximately 25% of the liver protein content daily. Within the range of values of this study, the absolute synthesis rate of albumin was not correlated to the fractional synthesis rate of total liver protein.

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The concentrations of the free amino acids in individual tissues gives information concerning amino acid, energy and protein metabolism. In muscle and intestinal mucosa, different metabolic states are distinctly characterized by an altered free amino acid pattern. Furthermore, the patterns are quite different in individual tissues. So far, liver tissue has not been investigated systematically in this respect. The aims of this investigation were to establish a standardized sampling procedure for liver tissue during laparoscopic surgery and to characterize the free amino acid concentrations in human liver tissue. Aspartate was the most abundant amino acid in the liver, followed by taurine, glutamine, glutamate, glycine and alanine. These six, and most abundant, amino acids constitute 90% of the total hepatic amino acid concentration. In the future, liver tissue sampling during laparoscopic surgery may be used as a model for investigating the influence of nutrition and hormones on hepatic amino acid and protein metabolism in man.

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