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Biomedical subjects

J Wernerman

Publications and source records attributed to J Wernerman.

At least 55 records · Page 3Linked to original sources

Enteral nutrition in intensive care patients: a practical approach.

Severe protein-calorie malnutrition is a major problem in many intensive care (ICU) patients, due to the increased catabolic state often associated with acute severe illness and the frequent presence of prior chronic wasting conditions. Nutritional support is thus an important part of these patient's management. Over the years, enteral nutrition (EN) has gained considerable popularity, due to its favorable effects on the digestive tract and its lower cost and rate of complications compared to parenteral nutrition. However, clinicians caring for ICU patients are often faced with contradictory data and difficult decision-making when having to determine the optimal timing and modalities of EN administration, estimation of patient requirements and choice of formulas. The purpose of this paper is to provide practical guidelines on these various aspects of enteral nutritional support, based on presently available evidence.

Contraindications↗

Inter-organ fluxes in a methodological perspective.

Inter-organ fluxes remain a cornerstone as an investigating tool in metabolic research. Combination with isotopic labelling and microdialysis have now opened new possibilities of addressing a number of questions not previously accessible. However, the technique requires a high level of knowledge among investigators as well as among readers.

Amino Acids↗

Modulation of endogenous glutathione availability.

Glutathione is quantitatively the most important antioxidant and scavenger. In addition it has a number of important functions in amino acid transport across membranes, in protein synthesis and degradation, in gene regulation and in cellular redox regulation. It becomes more and more evident that depletion of glutathione is associated with states of severe diseases. From this perspective, the possibility of manipulating the availability of glutathione becomes a very attractive form of treatment. In this review, new insights into pathophysiology and the regulation of glutathione metabolism, in addition to effects of precursors to and stimulants of glutathione synthesis, are covered. It is very likely that glutathione precursors will soon be an important pharmacological tool for treatment in a number of diseased states.

Acetylcysteine↗

Depression of liver protein synthesis during surgery is prevented by growth hormone.

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.

Adult↗

Inhibition of liver protein synthesis during laparoscopic surgery.

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.

Adult↗

[Effect of transcutaneous electric muscle stimulation on postoperative muscle mass and protein synthesis].

In an experimental study, 13 patients undergoing major elective abdominal surgery were given postoperative transcutaneous electrical muscle stimulation (TEMS) to the quadriceps femoris muscle on one leg, where the opposite leg served as a control. Changes in cross sectional area (CSA) and muscle protein synthesis were assessed by CT-scan and percutaneous muscle biopsies for ribosome analysis before surgery and on the sixth postoperative day. The percentage of polyribosomes in the ribosome suspension decreased significantly (p < 0.03) after operation in control legs, but not in stimulated legs (p > 0.16). The total concentration of ribosomes decreased significantly in TEMS legs (p < 0.03), but not in control legs (p > 0.16) CSA decreased significantly in both legs. The decrease in polyribosomes and CSA after operation was significantly less in TEMS legs than in controls (p < 0.05). TEMS may be a simple and effective method to improve muscle protein synthesis and muscle mass after abdominal surgery and should be evaluated in other catabolic states with muscle wasting.

Adult↗

Enteral nutrition in intensive care patients: a practical approach. Working Group on Nutrition and Metabolism, ESICM. European Society of Intensive Care Medicine.

Severe protein-calorie malnutrition is a major problem in many intensive care (ICU) patients, due to the increased catabolic state often associated with acute severe illness and the frequent presence of prior chronic wasting conditions. Nutritional support is thus an important part of the management of these patients. Over the years, enteral nutrition (EN) has gained considerable popularity, due to its favorable effects on the digestive tract and its lower cost and rate of complications compared to parenteral nutrition. However, clinicians caring for ICU patients are often faced with contradictory data and difficult decisions when having to determine the optimal timing and modalities of EN administration, estimation of patient requirements, and choice of formulas. The purpose of this paper is to provide practical guidelines on these various aspects of enteral nutritional support, based on presently available evidence.

Cost-Benefit Analysis↗

Renal effects of alpha-ketoglutarate early after coronary operations.

BACKGROUND: Alpha-ketoglutarate (alpha-KG) is a Krebs cycle intermediate and the carbon skeleton of glutamate. Alpha-ketoglutarate has provoked interest in heart surgery because of its proposed critical role in myocardial metabolism. This study investigates the role of alpha-KG in renal function after cardiac surgical procedures. METHODS: Twenty-two patients with normal preoperative renal function were included in a prospective, randomized, and controlled study. Eleven patients received intravenous infusion of 30 g alpha-KG/hour after the operation. Measurements were performed before operation, immediately after operation, and after 30 minutes of alpha-KG infusion. RESULTS: Renal blood flow was higher during alpha-KG infusion, 297% +/- 97% (of preoperative value), than in controls, 125% +/- 20% (p < 0.05). Filtration fraction was lower (12.3% +/- 0.05% versus 17.2% +/- 1.1%, p < 0.01), which prevented a significant difference in glomerular filtration rate. The renal arteriovenous differences of lactate, glutamate, glutamine, and glycine changed toward a net release during alpha-KG infusion. CONCLUSIONS: Infusion of alpha-KG enhances renal blood flow early after coronary surgical procedures in patients with normal renal function. The mechanism is unclear, but could be associated with primarily metabolic effects, and may potentially convey a beneficial effect for renal function.

Adult↗

Effects on skeletal muscle amino acids and whole body nitrogen metabolism of total parenteral nutrition following laparoscopic cholecystectomy and given to healthy volunteers.

In this descriptive study total parenteral nutrition (TPN) without glutamine was administered over 2 days to patients undergoing laparoscopic cholecystectomy (n = 8) and to volunteers (n = 8). Effects on muscle amino acids and nitrogen economy were studied. Muscle protein synthesis, determined by ribosome and polyribosome concentrations were measured in the patients. In both patients and volunteers the muscle amino acid patterns indicated muscle protein catabolism. Decreases in glutamine were seen in both groups (21.8 +/- 4.6% in patients and 17.5 +/- 5.4% in the volunteers). In both groups a negative nitrogen balance was seen (-4.1 +/- 1.2 gram and -10.3 +/- 2.4 gram respectively). The patients also showed decreased ribosome (by 13.7 +/- 4.5%) and polyribosome concentration (by 17.4 +/- 4.6%), indicating a decrease in muscle protein synthesis. No comparisons are made between the two groups since they are not comparable. However, it is concluded in these two descriptive studies, that during these conditions, TPN does not prevent muscle protein catabolism either during basal conditions or after a minor surgical trauma such as laparoscopic cholecystectomy.

Amino Acids↗

The effect of unloading on protein synthesis in human skeletal muscle.

Atrophy of skeletal muscle is observed in response to immobilization and lack of weight-bearing. The aim of this study was to investigate the effect of immobilization on muscle protein synthesis and associated biochemical parameters in skeletal muscle of healthy volunteers employing a standardized model of lower limb unloading. One leg was unloaded for 10 days, and percutaneous muscle biopsies were taken before and at the end of the unloading period. The capacity for protein synthesis, as reflected by the concentration of RNA, decreased by 16% (P < 0.05) although the fractional synthesis rate (FSR) of protein was not significantly changed after 10 days of unloading. Furthermore there was an increase in the concentration of the free branched chain amino acids in muscle by 48% (P < 0.05).

Adult↗

Tissue protein synthesis rates in critically ill patients.

OBJECTIVES: The aims of this study were to simultaneously determine the in vivo rates of protein synthesis in skeletal muscle, peripheral blood lymphocytes, and serum albumin in critically ill patients; to establish whether a relationship between the responses of these tissues could be observed; and to demonstrate if a protein synthesis pattern characteristic of critical illness exists. DESIGN: Descriptive study. SETTING: Intensive care unit of a 1000-bed university hospital. PATIENTS: Fifteen patients treated in the intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Rates of tissue protein synthesis were determined in vivo once during the course of critical illness, using the flooding method with L-(2H5)phenylalanine. Protein synthesis in muscle was 1.49 +/- 0.16%/day; in circulating lymphocytes (i.e., mononuclear cells), protein synthesis was 11.10 +/- 1.82%/day. Albumin synthesis was 12.81 +/- 1.23%/day when expressed as the fractional rate, and was 184 +/- 19 mg/kg/day when expressed as the absolute rate. CONCLUSIONS: The individual tissues responded differently to trauma, and showed a wide range of values. The responses were not significantly correlated with each other and no pattern of tissue protein synthesis characteristic of critical illness was observed. However, both muscle protein and albumin synthesis rates correlated with metabolic status and clinical indices of the severity of illness.

Adult↗

Surgical trauma decreases glutathione synthetic capacity in human skeletal muscle tissue.

To gain insight into cellular metabolism underlying the glutathione (GSH) alterations induced by surgical trauma, we assessed postoperative skeletal muscle GSH metabolism and its redox status in 10 patients undergoing elective abdominal surgery. Muscle biopsy specimens were taken from the quadriceps femoris muscle before and at 24 and 72 h after surgery. GSH concentrations decreased by 40% at 24 h postoperatively compared with the paired preoperative values (P < 0.001) and remained low at 72 h (P < 0.01). The concentration of GSH disulfide (GSSG) did not significantly change throughout the study period, whereas the total GSH (as GSH equivalent) concentration decreased after surgery. Of the GSH constituent amino acids, the concentration of cysteine remained unchanged throughout the study period (from 28.2 +/- 10.1 preoperatively to 29.4 +/- 13.9 at 24 h postoperatively and to 28.3 +/- 15.6 micromol/kg wet wt at 72 h postoperatively). Despite a reduction in glutamate concentration by 40% 24 h after surgery, no correlation was established between GSH and glutamate concentrations postoperatively. Activity of gamma-glutamylcysteine synthetase did not change significantly after surgery, whereas GSH synthetase activity decreased postoperatively (from 66.4 +/- 19.1 preoperatively to 41.0 +/- 10.5 24 h postoperatively, P < 0.01, and to 46.0 +/- 11.7 microU/mg protein 72 h postoperatively, P < 0.05). The decrease of GSH was correlated to the reduced GSH synthetase activity seen at 24 h postoperatively. These results indicate that the skeletal muscle GSH pool is diminished in patients after surgical trauma. The depletion of the GSH pool is associated with a decreased activity of GSH synthetase, indicating a decreased GSH synthetic capacity in skeletal muscle tissue.

Aged↗

The synthesis rates of total liver protein and plasma albumin determined simultaneously in vivo in humans.

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.

Adult↗

Addition of alpha-ketoglutarate to blood cardioplegia improves cardioprotection.

BACKGROUND: We hypothesized that myocardial content of alpha-ketoglutarate (alpha-KG), an intermediate of the Krebs cycle, can be critically low during heart operations, and that provision of alpha-KG could reduce metabolic abnormalities and lead to improved myocardial protection. METHODS: Twenty-four men aged 46 to 78 years who were undergoing heart operations participated in a prospective, controlled, randomized study. In 13 patients, an average of 28 g of alpha-KG was added to blood cardioplegia. Plasma creatine kinase isoenzyme MB and troponin T, and myocardial extraction of oxygen, substrates, and amino acids were measured. RESULTS: alpha-Ketoglutarate treatment was associated with lower creatine kinase isoenzyme MB (F = 39.6, df = 1.172, p < 0.001) and lower troponin (F = 12.9, df = 1.172, p < 0.001). The values at 4 hours were 31 +/- 2.4 microg/L versus 49 +/- 4.9 microg/L (creatine kinase isoenzyme MB) and 1.1 +/- 0.05 microg/L versus 2.0 +/- 0.34 microg/L (troponin T). Myocardial oxygen extraction was higher during alpha-KG cardioplegia (p < 0.01), but there were no significant differences in myocardial uptake or release of substrates or amino acids. Lactate release was observed in both groups during cardioplegia. Myocardial lactate release had ceased after 30 minutes of reperfusion in nearly half the alpha-KG-treated patients (6 of 13) but remained in all the control patients (11 of 11, p = 0.016). There were no other differences after 30 minutes of reperfusion. CONCLUSION: Provision of alpha-KG during blood cardioplegia improves myocardial protection in patients undergoing coronary operations. This may be linked to enhanced oxidation.

Aged↗

Insulin and amino acid infusion after cardiac operations: effects on systemic and renal perfusion.

OBJECTIVE: The purpose of this study was to answer two questions: (1) Does a mixed amino acid infusion enhance systemic and renal perfusion in the early postoperative period after heart operations? (2) Does the addition of insulin (glucose-insulin-potassium solution) provide additional effects to those of an amino acid infusion? METHODS: Thirty-three male patients undergoing coronary artery bypass grafting (mean age 65.9 +/- 1.2 years) were included in a prospective, controlled, randomized study. Eleven patients (AA group) received infusion of mixed amino acids (11.4 gm), 11 patients (AA + GIK group) received infusion of mixed amino acids (11.4 gm) and insulin solution (225 IU insulin, glucose with glucose clamp technique, and potassium), and 11 patients served as control subjects. RESULTS: Amino acid infusion alone had no effect on systemic vascular resistance or cardiac index but increased renal blood flow 51% +/- 11% (from 114 +/- 13 to 172 +/- 24 ml.min-1.m-2 in one kidney, p < 0.05 vs the control group). Insulin solution in addition to amino acid infusion reduced systemic vascular resistance 24% +/- 3% (from 1280 +/- 85 to 960 +/- 57 dyn.sec.cm-5, p < 0.05 vs the control and AA groups) and increased cardiac index 13% +/- 3% (from 2.3 +/- 0.2 to 2.6 +/- 0.2 L.min-1.m-2, p < 0.05 vs the control and AA groups). Insulin had no significant additive effect on renal blood flow. CONCLUSIONS: Our data imply that (1) infusion of mixed amino acids enhances renal blood flow after cardiac operations but has no effect on systemic perfusion and (2) the addition of insulin solution improves systemic perfusion. The combined treatment may potentially reduce the risk of renal hypoperfusion injury in the postoperative period after coronary artery bypass grafting.

Adult↗