Home parenteral lipids in AIDS: a three-month study.

Parenteral nutrition is a part of the nutritional support regimen of patients with AIDS-associated wasting syndrome and gastrointestinal dysfunction. The cholesterol (CHOL) level in human immunodeficiency virus (HIV) membrane is very high, and recent lipid formulations with high phospholipid (PL) content have demonstrated the ability to trap CHOL from endogenous sources, modifying the composition of cell membranes. We administered lipid-based home parenteral nutrition for 3 mo to malnourished AIDS patients. The patients were randomly divided into two groups: 23 received the regular 20% fat emulsion formulation, and 27 received a 2% formulation enriched 10-fold with PLs but containing the same amount of triglycerides. All patients gained weight and improved their activity level. Those receiving the high-PL composition showed increased serum CHOL concentrations (from 147 to 241 mg/dL; P < 0.01), but no increase was seen in the number of CD4 cells or improvement in immune function. HIV infectivity was not modified. Patients receiving regular PLs had significantly decreased (P < 0.02) IgA concentrations (from 776 to 300 mg/dL) and improved mitogen response to phytohemagglutinin and to concanavalin A. This formula, too, had no effect on HIV infectivity. We conclude that standard parenteral nutritional influences the nutritional and immune status of malnourished AIDS patients. A PL-enriched parenteral formulation can trap CHOL, but it does not affect the immune profile or HIV infectivity in patients with advanced disease.

The use of an intravenous fish oil emulsion enriched with omega-3 fatty acids in patients with cystic fibrosis.

The effects of parenteral nutrition supplemented with a lipid emulsion enriched with the omega-3 fatty acids (FA), eicosapentaenoate (20:5n-3) and docosahexaenoate (22:6n-3), derived from fish oil were compared to a standard lipid emulsion containing omega-6 FA in patients with cystic fibrosis (CF). Patients were randomized to receive either Omegavenous 10%, which contains fish oil (IFO), or Liposyn III 10% (control) daily for 1 mo at a dose of 150 mg/kg. There were no observed allergic or toxic reactions, no abnormalities in liver function tests or coagulation parameters. To assess the bioavailability of the lipid administered, measurement of plasma free fatty acid (FFA) levels were made of the essential FA. There were no adverse changes in plasma levels of the omega-6 FA (18:2n-6, 18:3n-6, 20:3n-6, and 20:4n-6), and plasma levels of the omega-3 FA (20:5n-3 and 22:6n-3) increased significantly during the 1-mo study. There were no significant changes in plasma FFA profiles of the essential FA for the patients receiving the control lipid. The effect of treatment on pulmonary function was also investigated. There were no significant changes in FVC, FEV1, PEFR, FEV1/ FVC, or FEF25-75 (absolute value or percentage) over the 4 weeks of study in the group receiving IFO or control. This preliminary investigation suggests that intravenous administration of fish oils enriched with long chain omega-3 FA to patients with CF is safe and bioavailable.

The antinociceptive effects of branched-chain amino acids: evidence for their ability to potentiate morphine analgesia.

The effect of branched-chain amino acids (BCAA) on pain threshold was studied in rats. Nociception was induced by the hot-plate analgesia meter, a method measuring supraspinally organized pain responses. After a single intravenous injection of BCAA (320 mg/kg), the percent change in latency time to the pain response significantly increased by 19% in 60 min, and by 22% in 75 min (p < 0.005), as compared to an injection of an equal volume of a standard concentration of an amino acid solution or physiological saline. Subsequently, we studied the interaction of BCAA with opioid-type analgesia. In combination with intravenously injected morphine (3 mg/kg), BCAA significantly potentiated and prolonged the action of morphine using the hot-plate test. From 5 min after morphine injection, the latencies to a pain response were markedly higher with the combination of BCAA and morphine (+80% and +89% at 5 min after morphine injection, if BCAA was administered 45 or 60 min prior to morphine injection, respectively) when compared with the effect of morphine alone (+13% at 5 min; p < 0.005). BCAA demonstrated analgesic effects, which, in combination with morphine, potentiated and prolonged the antinociceptive action of morphine. BCAA may represent a new adjunct treatment modality for acute and chronic pain, and give us further insight into the mechanisms of pain control.

Effect of substrate manipulation on reducing ischemia/reperfusion injury in isolated perfused rat hearts.

The objective of this investigation was to assess the effect of substrate manipulation on reducing ischemia/reperfusion injury (IRI). Isolated rat hearts were perfused with modified Krebs-Henseleit buffer containing either (in mM): glucose 11 (G1), glucose 22 (G2), or glucose 11 with either xylitol 11 (GX), mannitol 11 (GM), L-leucine 1 (GL), or L-glutamic acid 2 (GGA), respectively. Hearts were subjected to 10 min of global no-flow ischemia, followed by 20 min of reperfusion. Mean tissue perfusion, oxygen consumption, and peak left ventricular pressure (PLVP) were determined at baseline, in the first minute of regular heart rhythm following ischemia, and after 20 minutes of reperfusion. Reperfusion arrhythmia (in sec) was significantly (all p < 0.05) shorter in GGA (115 +/- 33) vs G1 (315 +/- 29) and G2 (273 +/- 33), and also in GL (161 +/- 26) vs G1. Dry/wet heart weight ratios were also greater in GGA (0.20), when compared with G2 (0.16), GX (0.17), GM (0.17), GM (0.17), and GL (0.17) (all p < 0.02), suggesting less cellular/interstitial edema. Percent recovery in PLVP was improved (p < 0.03) in GL (81 +/- 2) and GGA (81 +/- 2) vs. G2 (71 +/- 3), without significant alterations in oxygen consumption. Thus, cardiac IRI can be diminished by substrate manipulation, especially by augmentation of glutamate and leucine, most likely due to an improved anaerobic energy generation and utilization.

[Fat-rich diets in patients with mild chronic obstructive lung disease (COPD)]. / Dietas ricas en grasa en pacientes con enfermedad pulmonar obstructiva crónica (EPOC) leve.

A study was made in stable patients suffering from mild COLD of the maximum capacity for ergometric cycle exercise and gas exchange at rest and during maximum exercise, measured by indirect calorimetry. During the period of study (3 months) one group of patients receive the usual diet while the other received an oral nutritional supplement rich in fats an minimum of 75% of their energy expenditure measured at rest. The patients studied, with mild COLD, were hypermetabolic, and although at rest they presented indirect calorimetry data such as would correspond to similar subjects, during exercise not just the limit on exercise became clear but also the alteration to ventilatory capacity and gas exchange. The fat-rich nutritional supplement administered for three months did not succeed in enhancing exercise capacity or in altering gas exchange during maximum exercise is stable patients with mild COLD.

Short-term effects of lipid-based parenteral nutrition in patients with acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia.

The human immunodeficiency virus (HIV) is surrounded by a rigid membrane rich in cholesterol. Extraction of cholesterol from the virus envelope reduces its infectivity in vitro. Large amounts of lipid emulsion phospholipids have the property of extracting cholesterol from cell membranes. The purpose of the present study was to observe the effects of high phospholipid loads on the lipid profile as well as HIV infectivity of patients with acquired immunodeficiency syndrome (AIDS). Fifty-nine patients with AIDS, weight loss, and presenting Pneumocystis carinii pneumonia (PCP) were included in a prospective, randomised, controlled study. In addition to standard therapy, patients received for 2 weeks 910 kcal of peripheral parenteral nutrition including 20% lipid emulsion (group 1) or a new 2% lipid emulsion with a high phospholipid/triglyceride ratio (1:1.7) (group 2). Activity level and biological, immune and HIV load and infectivity parameters were followed. Cholesterol increased from 113 +/- 44 to 228 +/- 103 mg/dl in the 2% group (P < 0.00001). Triglycerides also increased significantly (P < 0.02). IgA was decreased in the 2% group. HIV load and infectivity tests and leukocyte subsets did not demonstrate any effect of the lipid emulsions. It is concluded that the new 2% emulsion is a powerful cholesterol extractor. However, 2 weeks' administration failed to show any efficacy in modifying immune parameters or HIV infectivity in AIDS patients with PCP.

Gastric emptying in humans: influence of different regimens of parenteral nutrition.

Intravenous administration of nutrients can suppress oral food intake. Inhibition of gastric emptying (GE) is a potential explanation for this process. Inhibition of GE during parenteral nutrition (PN) and attenuation of this by parenteral nutrition enriched with branched-chain amino acids (BCAAs) was examined in nine healthy males maintained on standard liquid diets for 6 d before each of three GE studies. GE was measured by scintigraphy after ingestion of a liquid test meal, at weekly intervals, after a 6-h infusion of Ringer lactate solution (RL), peripheral PN, or PN with half the amino acids replaced with BCAAs (BCPN). With PN, gastric emptying during the first 50 min was delayed by 38% compared with RL infusion; BCPN attenuated the effect, suggesting that postabsorptive control of food intake may act through changes in GE. These findings have clinical potential to reduce interference with appetite and to optimize food intake during PN administration.

Branched-chain amino acids and respiratory pattern and function in the neonate.

Branched-chain amino acids (BCAA) increase respiratory drive in adults and improve diaphragmatic function in vitro. This study was designed to examine the effects of increased amounts of BCAA in intravenous nutrition on respiratory function and episodes of apnea in premature infants. An open cross-over design was used, with each patient serving as his own control. Ten premature infants, 34 weeks' gestation or less, were observed. Mean gestational age was 30.6 weeks (range 27 to 33 weeks), mean birth weight was 1487 gm +/- 300 gm, and the age at study was 5 to 33 days. For three consecutive 24-hour periods, the infants received routine total parenteral nutrition (TPN) (30% BCAA), enriched TPN (53% BCAA), and routine TPN (30% BCAA). Pulmonary function, apnea frequency, blood chemistry, and amino acid pattern were measured. Enriched TPN resulted in significant increases in all infants in dynamic compliance, from 2.41 +/- 1.07 to 4.55 +/- 2.78 ml/cm H2O (p < 0.025), and in specific dynamic compliance from 1.67 +/- 0.64 to 3.1 +/- 1.51 ml/cm H2O/kg (p < 0.005). Total pulmonary resistance decreased from 40.3 +/- 23.3 to 24.0 +/- 20.9 cm H2O/L/sec (p < 0.05), and peak-to-peak pressure decreased from 5.96 +/- 0.93 to 4.09 +/- 2.34 cm H2O (p < 0.05). All values returned to baseline with resumption of the routine TPN. In four infants with significant apnea, the average number of episodes of apnea decreased from 58 during standard TPN to 11 with the enriched solution infusion during matched 12-hour periods (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of valine, leucine, isoleucine, and a balanced amino acid solution on the seizure threshold to picrotoxin in rats.

During infusion of branched-chain amino acids (BCAAs) in humans, changes in ventilatory drive, sleeping pattern, and appetite have been reported. The mechanism by which BCAA exerts their effects on CNS remains unclear. An infusion of a BCAA solution (300 mg/kg) has previously been found to increase the seizure threshold in rats to the proconvulsant drug picrotoxin, an antagonist on the GABA-benzodiazepine receptor complex. In this study, each of the BCAAs given separately (valine, leucine, isoleucine; 300 mg/kg) (n = 10) increased the mean latency time to onset of seizures vs. placebo as an indication of an increased seizure threshold. A balanced amino acid solution (Vamin-Glucose) had no effect on the seizure threshold. Thus, these CNS effects are specific for BCAAs and occur with all three.

Inhibition of lymphocyte proliferation in vitro by two lipid emulsions with different fatty acid compositions.

The effects of two lipid emulsions upon the proliferation of rat and human lymphocytes in vitro were investigated. The emulsions used were Intralipid, a soya bean oilbased emulsion in widespread clinical use, and Omegavenous, a newly-developed emulsion in which n-3 polyunsaturated fatty acids comprise approximately 40% of the total fatty acids. Both emulsions inhibited lymphocyte proliferation in a concentration- and time-dependent manner. Omegavenous was a much more potent inhibitor than Intralipid.

Impact of specific substrate supply on efficiency of cardiac function: an update.

Investigations of the mechanisms that modulate energy generation during states of altered cardiac metabolism have reached a point where there is both need and demand for novel approaches. The evidence discussed here strongly suggests that both energy generation and utilization in these states may be effectively strengthened by nutritional manipulation. Compared with standard treatments for ischemia/reperfusion injury or heart failure, nutritional therapy may present an important and less toxic approach by affecting the mechanisms of energy utilization during compromised cardiac states. We provide not only a conceptual framework for further experimental studies of myocardial metabolism during ischemia and reperfusion injury but also a basis for developing clinically applicable nutrients designed to improve deranged cardiac function. The use of traditional energy substrates, in conjunction with those that may be conditionally important during compromised cardiac states, potentially offers a useful therapeutic modality in the treatment of the cardiac patient.

[Enteral nutrition of critically ill patients]. / Enterale Ernährung bei kritisch kranken Patienten.

OBJECTIVE: The purpose of this article is to review the facilities of early enteral nutrition in critically ill patients. DATA SOURCES: Review articles as well as original papers are the main sources for this contribution. SELECTION CRITERIA: Pathophysiologic conditions of intestinal substrate assimilation during hypermetabolism are described. The resulting consequences for enteral alimentation are discussed. Practical aspects such as classification and different indications of formulas, performance of enteral nutrition as well as management of tube feeding complications are further subjects of this review. RESULTS: Paying attention to tolerance, enteral nutrition can be started early in the postoperative or posttraumatic course. Jejunal substrate application, however, reveals to be a major issue for successful management. CONCLUSION: Clinical performance as well as efficiency of enteral nutrition seem to be essentially dependent on the intestinal blood flow. New methods for estimating intestinal blood flow, such as tonometry, will have to be evaluated especially in critically ill patients to improve the indications for enteral nutrition.

[The non-energetic importance of enteral nutrition of critically ill patients]. / Nichtenergetische Bedeutung der enteralen Ernährung bei kritisch kranken Patienten.

OBJECTIVE: The aim of this review is to describe recently discussed nonenergetic effects of enteral nutrition. DATA SOURCES: Results of current animal and clinical studies are summarized and the place of enteral nutritional regimen in critically ill patients is discussed. SELECTION CRITERIA: The possible protective effect of early enteral nutrition in critically ill patients concerning stress ulcus prophylaxis, infections, and the pathogenesis of multiple organ failure is gaining particular attention in this review. RESULTS: The reduction of intestinal bacterial translocation and the decline of catabolism during enteral substrate application seems to be proven by animal experiments. CONCLUSION: The relevance of early enteral nutrition in critically ill patients, however, needs to be investigated in further clinical studies.

Long-term parenteral nutrition in cystic fibrosis.

The effects of parenteral nutrition (PN) with high lipid content were studied in 18 cystic fibrosis patients in this pilot investigation. The patients were randomly assigned to one of two groups. During the first 4-mo period, group 1 received PN and group 2 received routine therapy. During the second 4-mo period, PN was discontinued in group 1 and instituted in group 2. When the effect of PN was considered for both treatment groups, its general effect was to increase body fat content with little or no impact on respiratory function, exercise tolerance, or recurrent infections. However, subsequent analysis and clinical observation suggested that patients receiving PN responded in two seemingly distinct patterns: some demonstrated apparent clinical improvement and benefit, and others did not. A positive response in pulmonary and exercise function was closely correlated to a rise in serum dihomo-gamma-linolenic acid (DHLA) concentrations during PN. Pulmonary function improved in patients who normalized their DHLA levels (vital capacity increased from 2.2 +/- 0.3 to 2.6 +/- 0.3 area %, p < 0.05), whereas those who continued to have undetectable levels of DHLA deteriorated (forced expiratory volume in 1 s decreased from 0.7 +/- to 0.6 +/- 0.1, p < 0.001). PN applied to malnourished patients with cystic fibrosis results in beneficial effects in a subgroup characterized by the presence of DHLA in serum; for the group as a whole, the positive effects are minimal.

Branched-chain amino acids increase the seizure threshold to picrotoxin in rats.

During infusion of branched-chain amino acids (BCAAs) in humans, changes in ventilatory drive, appetite, and sleep have been reported. The mechanism by which BCAAs exert their effects on CNS remains unclear. Picrotoxin is a proconvulsant drug, acting as an antagonist on the GABA-benzodiazepine receptor complex. Twenty rats were randomized to receive either an IP injection with 4% BCAAs (300 mg/kg; 8 ml/kg) (n = 10) or placebo (saline 8 ml/kg) (n = 10). The mean latency time from injection to onset of seizures was recorded as an indication of the seizure threshold. Latency time was significantly longer for BCAAs than for placebo, 11.2 (+/- 1.9) vs. 8.3 (+/- 1.8) min. Thus, a BCAA injection increased the seizure threshold to picrotoxin (p < 0.03). This suggests that BCAA infusion may exert effects on the GABA-benzodiazepine receptor complex.

Hypercaloric glycerol in injured patients.

BACKGROUND: This study investigates the effects of glycerol as a fuel source in the hypermetabolic patient (after injury). METHODS: Twenty-two patients were studied after multiple trauma and randomly assigned to either glucose or glycerol as the carbohydrate source (220 gm glycerol or 320 gm dextrose) during a lipid-based system of parenteral nutrition. In the immediate postoperative period, measurements were made of nitrogen balance, substrates, energy expenditure, insulin, glucagon, and liver function tests. RESULTS: In the glycerol group glucose concentrations in plasma were significantly lower, whereas glycerol levels increased nearly twentyfold. Insulin and glucagon levels increased in both groups; however, the rise in insulin level was greater in the glucose group, whereas glucagon increased in both groups to a similar degree. Nitrogen balance was restored to equilibrium in the glycerol group while remaining negative in the glucose group. No abnormalities in liver function test results or differences in serum albumin levels were noted in either group. A 12% thermic effect was noted in the glucose group but not in the glycerol group. CONCLUSIONS: Glycerol seems to be a viable fuel source in the traumatized patient, being associated with nitrogen retention and minimal thermal effect. A marked rise in plasma levels of glycerol does occur, but this does not appear to have any associated toxicity.