Studies with a safflower oil emulsion in total parenteral nutrition.

The prevention of essential fatty acid deficiency and the provision of adequate amounts of energy are two major concerns in total parenteral nutrition. Since earlier preparations of fat emulsion used to supplement the usual regimen of hypertonic glucose and amino acids have widely varying clinical acceptability, a new product, a safflower oil emulsion available in two concentrations (Liposyn), was evaluated. In four clinical trials the emulsion was used as a supplement to total parenteral nutrition. In five surgical patients 500 ml of the 10% emulsion infused every third day prevented or corrected essential fatty acid deficiency; however, in some cases in infusion every other day may be necessary. In 40 patients in severe catabolic states the emulsion provided 30% to 50% of the energy required daily: 10 patients received the 10% emulsion for 14 to 42 days, 9 patients received each emulsion in turn for 7 days, and 21 patient received the 20% emulsion for 14 to 28 days. All the patients survived and tolerated the lipid well; no adverse clinical effects were attributable to the lipid infusions. Transient mild, apparently clinically insignificant abnormalities in the results of one or more liver function tests and eosinophilia were observed in some patients. Thus, the safflower oil emulsion, at both concentrations, was safe and effective as a source of 30% to 50% of the energy required daily by seriously ill patients.     

Indications for total parenteral nutrition in the hospitalized patient: a prospective review of evolving practice

The indications for initiating total parenteral nutrition (TPN) were prospectively evaluated in 100 consecutive patients at a tertiary referral hospital with a long-standing Nutritional Support Service to illustrate the reasons why the parenteral route was chosen at this unique institution in terms of patient population. Sixty male and 40 female patients, average age 59 +/- 17 years (range 22-86 years), were classified a priori as to the underlying reasons for initiation of TPN. The study was conducted by a Nutrition Support Service at this hospital without pediatric, trauma, or burn services specializing in the care of patients with diabetes mellitus. Of the 100 patients, 63% were from the surgical service; 24% had diabetes mellitus. Their mean weight (118 +/- 29% of ideal), body mass index (25 +/- 6 kg/m(2)), and serum albumin (2.8 +/- 0.7 g/dL) indicated a reasonable body composition with a moderate systemic inflammatory response. Six patients received preoperative TPN for an average of 5 +/- 3 days with a variety of diagnoses including malignancy, Crohn's disease, bowel obstruction, and gastrointestinal bleeding. The underlying reasons for initiating nutritional support were related to three factors that largely determine the need for involuntary feeding: preexisting protein calorie malnutrition, actual or anticipated semistarvation for a prolonged period, and the presence of a systemic inflammatory response. The choice of TPN was based on anticipated or proven intolerance to full enteral feeding. The duration of time before initiation of TPN postoperatively was 6 +/- 5 days, which reflects our policy that initially well-nourished patients who are experiencing a systemic inflammatory response should not undergo more than 5 to 7 days of inadequate feeding. The duration of TPN overall was 11 +/- 10 days, which primarily illustrates the dramatic reduction in length of hospital stay that has occurred throughout the health care system and the willingness to provide TPN in alternative settings including transitional care units, rehabilitation hospitals, and for short-term care, the patient's home. The most common specific reasons identified for initiating TPN rather than enteral nutrition were ileus (25%), an underlying acid-base or electrolyte/mineral disorder (13%) requiring correction, and the convenience of TPN because a central venous catheter was in place (12%). The usual indication for nutritional support at this tertiary referral and specialty hospital was actual or impending protein calorie malnutrition. TPN was chosen for a variety of reasons related to actual or anticipated tolerance to enteral feeding. This audit demonstrates that our TPN practice has evolved in relation to time of initiation and duration of feeding, which reflect a clearer appreciation of the risks and benefits of TPN.     

Anabolic effectiveness of nitrogenous preparations for parenteral nutrition in the presence of toxic liver damage]

The authors studied the assimilation of nitrogen preparations--moriamin S-2 and "improved" caseine hydrolysate in parenternal administration to 100 albino rats. Healthy animals and those with toxic affection of the liver induced with CCl4 were experimented upon. In healthy animals administration of nitrogen preparations led to the change of negative nitrogen balance into a positive one, normalized the content of blood and tissue amine nitrogen deranged in protein deficiency. Assimilation of nitrogen preparations fell considerably in toxic hepatitis. An 8-day parenteral nutrition failed to change the negative nitrogen balance into positive, and did not eliminate hypoproteinemia; however, it normalized the amine nitrogen concentration in the blood and tissues.     

Lipid emulsions for parenteral nutrition in critical illness

Critical illness is a life-threatening multisystem process that can result in significant morbidity and mortality. In most patients, critical illness is preceded by a physiological deterioration, characterized by a catabolic state and intense metabolic changes, resulting in malnutrition and impaired immune functions. In this context, parenteral lipid emulsions may modulate inflammatory and immune reactions, depending on their fatty acid composition. These effects appear to be based on complex modifications in the composition and structure of cell membranes, through eicosanoid and cytokine synthesis and by modulation of gene expression. The pathophysiological mechanisms underlying these fatty acid-induced immune function alterations in critical ill patients are however complex and partially understood. Indeed, despite a very abundant literature, experimental and clinical data remain contradictory. The optimization of lipid emulsion composition thus represents a major challenge for clinical medicine, to adequately modulate the inflammatory pathways. In the present review, we first address the metabolic response to aggression, the effects of parenteral lipid emulsions on inflammation and immunity, and finally the controversial place of these lipid emulsions during critical illness. The analysis furthermore highlights the pathophysiological mechanisms underlying the differential effects of lipid emulsions and their potential for improving the handling of critically ill patients.     

Hormone treatment of the adult transsexual patient

Hormonal reassignment has two aims: (1) to reduce the hormonally induced secondary sex characteristics of the original sex and (2) to induce the secondary sex characteristics of the new sex. In Europe, cyproterone acetate is generally used to inhibit androgens in male-to-female transsexuals. Medroxyprogesterone acetate is an acceptable, though less effective, alternative. To induce feminization there is a wide range of oestrogens. Oral ethinyloestradiol is a potent and inexpensive oestrogen, but it may cause venous thrombosis. Oral 17beta-oestradiol valerate or transdermal 17beta-oestradiol is the treatment of choice. The goal of treatment in female-to-male transsexuals is to induce virilization, including a male pattern of sexual hair, a male voice and male physical contours, and to stop menses. The principal hormonal treatment is a testosterone preparation. Hormone-dependent tumours have been encountered and surveillance is necessary.     

Short-time infusion of fish oil-based lipid emulsions, approved for parenteral nutrition, reduces monocyte proinflammatory cytokine generation and adhesive interaction with endothelium in humans

Potential impact of omega-3 fatty acids, as contained in fish oil, on immunological function has been suggested because observations of reduced inflammatory diseases in Greenland Inuit were published. A fish oil-based lipid emulsion has recently been approved for parenteral nutrition in many countries. We investigated the influence of a short infusion course of fish oil-based (omega-3) vs conventional (omega-6) lipid emulsion on monocyte function. In a randomized design, twelve healthy volunteers received omega-3 or omega-6 lipid infusion for 48 h, with cross-over repetition of the infusion course after 3 mo. Fatty acid profiles, monocyte cytokine release and adhesive monocyte-endothelium interaction were investigated. Resultant omega-6 lipid emulsion increased plasma-free fatty acids including arachidonic acid, whereas the omega-3/omega-6 fatty acid ratio in monocyte membranes remained largely unchanged. It also caused a tendency toward enhanced monocyte proinflammatory cytokine release and adhesive monocyte-endothelium interaction. In contrast, omega-3 lipid emulsion significantly increased the omega-3/omega-6 fatty acid ratio in the plasma-free fatty acid fraction and in monocyte membrane lipid pool, markedly suppressing monocyte generation of TNF-alpha, IL-1, IL-6, and IL-8 in response to endotoxin. In addition, it also significantly inhibited both monocyte-endothelium adhesion and transendothelial monocyte migration, although monocyte surface expression of relevant adhesive molecules (CD11b, CD18, CD49 days, CCR2) was unchanged. Although isocaloric, omega-3 and omega-6 lipid emulsions exert differential impact on immunological processes in humans. In addition to its nutritional value, fish oil-based omega-3 lipid emulsion significantly suppresses monocyte proinflammatory cytokine generation and features of monocyte recruitment.     

Heat-shock proteins and nucleolar hypertrophy in the liver of rat infused with methionine-free total parenteral nutrition

Infusing a methionine-free solution into rats for 7 days resulted in a marked enlargement of liver nucleoli. By the analysis of two-dimensional gel electrophoresis, a spot 'a' (76 kDa, pI 5.3) stained with Coomassie blue was observed to accumulate highly in liver cytosol from rat infused with methionine-free solution. Metabolically labeling experiments with [35S]methionine showed that 'a' was more heavily labeled in primary hepatocytes of rats infused with methionine-free solution than in those of control rat. To ascertain whether 'a' is one of stress proteins, primary hepatocyte cultures were incubated at 42 degrees C for 2 h. 'a' (76 kDa, pI 5.3) was slightly induced in control hepatocytes but not appreciably in hepatocytes from the treated rat. In contrast, two other spots 'b' (74 kDa, pI 5.6) and 'c' (74 kDa, pI 5.3) were highly induced at 42 degrees C in hepatocytes from control and treated rats. The antibody against the consensus sequence peptide of hsp70 family reacted with 'a' (76 kDa, pI 5.3) as well as 'b' and 'c'. Immunoblot analysis revealed that 'a' accumulates highly in hepatocytes of treated rats. These results indicate that infusion of methionine-free solution into rats induces one member of the hsp70 family in hepatocytes.     

Enteral bile acid treatment improves parenteral nutrition-related liver disease and intestinal mucosal atrophy in neonatal pigs

Total parenteral nutrition (TPN) is essential for patients with impaired gut function but leads to parenteral nutrition-associated liver disease (PNALD). TPN disrupts the normal enterohepatic circulation of bile acids, and we hypothesized that it would decrease intestinal expression of the newly described metabolic hormone fibroblast growth factor-19 (FGF19) and also glucagon-like peptides-1 and -2 (GLP-1 and GLP-2). We tested the effects of restoring bile acids by treating a neonatal piglet PNALD model with chenodeoxycholic acid (CDCA). Neonatal pigs received enteral feeding (EN), TPN, or TPN + CDCA for 14 days, and responses were assessed by serum markers, histology, and levels of key regulatory peptides. Cholestasis and steatosis were demonstrated in the TPN group relative to EN controls by elevated levels of serum total and direct bilirubin and also bile acids and liver triglyceride (TG) content. CDCA treatment improved direct bilirubin levels by almost fourfold compared with the TPN group and also normalized serum bile acids and liver TG. FGF19, GLP-1, and GLP-2 were decreased in plasma of the TPN group compared with the EN group but were all induced by CDCA treatment. Intestinal mucosal growth marked by weight and villus/crypt ratio was significantly reduced in the TPN group compared with the EN group, and CDCA treatment increased both parameters. These results suggest that decreased circulating FGF19 during TPN may contribute to PNALD. Moreover, we show that enteral CDCA not only resolves PNALD but acts as a potent intestinal trophic agent and secretagogue for GLP-2.