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The Centers for Disease Control has identified intravenous propofol, a lipid-based medication, as a cause of postoperative infections in hospitalized patients. It appears the increased risk results from poor aseptic technique in the preparation, storage and administration of extemporaneously prepared propofol infusions. An additional risk of preparing propofol injection includes glass particulate contamination when the ampule dosage form is used. The current study, therefore, examines the extrinsic particulate load between propofol syringes prepared from ampules and vials with and without the use of a filter needle. Ten operating room clinicians were asked to prepare propofol infusion from ampules using a standard needle and a special filter needle. A similar comparison was performed separately in the laboratory using propofol vials to deduce differences between the normal presence of fat globules and the adventitious introducion of glass particulates from propofol ampules. Partical size analysis was determined by a single-particle, optical-sensing device using laser light extinction. Aliquots of the unfiltered and filtered samples were analyzed in triplicate by number-weighting all particles greater than or equal to 1.75 micrometers (instrument threshold for detecting abnormal particles) and all particles5 micrometers and10 micrometers (theoretical physiologic threshold for producing embolic syndrome). Significant differences were noted between dosage forms with respect to the number of particulates present from the pre- to the postfiltrate samples. A reduction in very large particulates (10 micrometers) was observed from the ampules (P=0.034). No differences were noted for the smaller particles (1.75 micrometers,p= 0.333;5 micrometers, p=0.229). Of the propofol vial samples, no differences were noted for the larger particles (5 micrometers, p=0.575;10 micrometers, p=0.229). However. a significant increase in the number of particle size was noted for the smallest particles (1.75 micrometers, p=0.0001). This increase in the numbler of particles in the postfiltrate may reflect the effects of filtration in destabilizing lipid particles. The use of the 5 micrometer filter needle significantly reduced the amount of abnormally large particles (10 micrometers) from the ampule dosage form, whereas no difference was observed from the propofol vials. This implies the abnormal particles present were other than lipid and likely to be glass associated with ampule breakage, suggesting the 5 micrometer filter needle be a standard part of propofol therapy when preparing infusions from ampule dosage forms.

Since many end stage renal disease (ESRD) patients experi inflammation, malnutrition, and anemia, the interplay of these processes should be considered in the approach to patients treated with erythropoietin (EPO). This article reviews the interrelationship between these factors. The systemic inflammatory response caused by exposure to inflammatory stimuli results in anorexia and metabolic disturbances leading to protein calorie malnut tion as well as sequestration of iron and hyporesponsiveness to EPO. The implications of these effects and possible strategies to optimize anemia management in the presence of these conditions are discussed.

The bacterial lipopolysaccharide endotoxin induces a catabolic response characterized by resistance to multiple anabolic hormones. The objective of this study was to determine the effects of endotoxin on the GH signaling pathway in rat liver in vivo. After the iv injection of Escherichia coli endotoxin (1 mg/kg), there was a progressive decrease in liver STAT5 (signal transducer and activator of transcription-5) tyrosine phosphorylation in response to GH (40% decrease 6 h after endotoxin), which occurred in the absence of a change in abundance of the STAT5 protein. Endotoxin resulted in a rapid 40-fold increase in liver Janus family kinase-2 (JAK2) messenger RNA, followed by a 2-fold increase in JAK2 protein abundance. This was associated with a 50% decrease in phosphorylated/total JAK2 after GH stimulation. GH receptor abundance was unchanged, suggesting a postreceptor site of endotoxin-induced GH resistance. Rat complementary DNAs for three members of the suppressor of cytokine signaling gene family were cloned [cytokine-inducible sequence (CIS), suppressor of cytokine signaling-2 (SOCS-2), and SOCS-3] and, using these probes, messenger RNAs for SOCS-3 and CIS were shown to be increased 10- and 4-fold above control values, respectively, 2 h after endotoxin infusion. The finding of endotoxin inhibition of in vivo STAT5 tyrosine phosphorylation in response to a supramaximal dose of GH in the absence of a change in GH receptor abundance or total GH-stimulated JAK2 tyrosine phosphorylation provides the first demonstration of acquired postreceptor GH resistance. We hypothesize that this may occur through a specificity-spillover mechanism involving the induction of SOCS genes by cytokines released in response to endotoxin and subsequent SOCS inhibition of GH signaling.

In most chronic disease conditions, the systemic inflammatory response and its mediators play an essential pathogenic role. Protein calorie malnutrition, a prominent feature of end-stage renal disease (ESRD), also develops, largely as a consequence of the systemic inflammatory response. ESRD (uremia), dialysis, systemic metabolic acidosis, and infections activate the systemic inflammatory response. Elevations in C-reactive protein and depressions of serum albumin below 4 g/dL are found in more than 50% of ESRD patients undergoing dialysis. In many patients receiving dialysis, the impact of this acute-phase response on measures of iron metabolism limits the ability to diagnose iron deficiency. Furthermore, there are risks to iron administration, although data linking iron overload to risk of infection in dialysis patients is suggestive, not definitive. It seems reasonable to hypothesize that the greatest risk of iron administration is in patents who are already infected, and the greater risk would be to raise the serum iron level and transferrin saturation precipitously. The total-dose infusion method, which provides all iron required to correct deficiency in 1 dose, is more likely to produce side effects and rapidly raise serum iron levels and transferrin saturation. The use of low-dose intravenous iron supplementation (10 to 20 mg per dialysis treatment or 100 mg every second week) avoids iron overtreatment and should reduce adverse events. In ESRD patients receiving dialysis, the importance of the systemic inflammatory response in the development of protein calorie malnutrition, the impact of the acute-phase response on iron nutriture, and the response to erythropoietin therapy must be considered to achieve an understanding of the altered responses to nutritional therapy in this setting.

The purpose of this study was to determine the plasma triglyceride and phospholipid fatty acid (FA) composition of severely malnourished patients with chronic liver disease and to examine the effects of parenteral nutrition with a total nutrient admixture (TNA) on these profiles. Nine consecutive patients with end-stage chronic liver disease were compared with 35 patients admitted for elective surgery of upper gastrointestinal malignancy. Baseline laboratory values and the FA profiles of the plasma triglyceride and phospholipids were analyzed. FA profiles were also performed after infusion of a TNA including 33+/-7 g of lipid/24 hr for 7.9+/-4 days in the patients with chronic liver disease. Compared with control patients, the plasma phospholipid fatty acid analysis results (relative mole percentage) of patients with chronic liver disease were significantly lower in the two essential FA, linoleic acid (15.4+/-3.4% vs. 20.8+/-2.9%, P0.001) and alpha-linolenic acid (0.02+/-0.05% vs. 0.08+/-0.10%, P0.001). Similar changes were demonstrated in the FA composition of the triglyceride fraction. Short-term infusion of intravenous lipid resulted in a significant increase in linoleic acid in the triglyceride fraction (9.9+/-2.8% before supplementation vs. 20.7+/-9.4% after supplementation, P0.01) and a decrease in oleic acid (38.7+/-5.2% before supplementation vs. 29.3+/-7.5 after supplementation, P0.01). In conclusion, acute and chronic deficiencies of essential FA occurs in patients with chronic liver disease. The clinical significance of these deficiencies is unknown, but they potentially may impact on eicosanoid metabolism. Short-term supplementation with modest amounts of intravenous lipid has only a minimal effect on normalization of longer-chain fatty acids.

Based on a review of randomized, controlled clinical trials, enteral feeding improves septic morbidity in critically ill and/or malnourished patients. Enteral feeding may be better than parenteral feeding, but a definitive study is not available. Immune-enhancing diets further improve septic morbidity in critically ill and/or malnourished patients. Active components identified include arginine, glutamine, and omega-3 fats, but the relative efficacy of any single immune enhancing component versus their combination is impossible to state based on the presently available evidence.

Liver transplantation has progressed from an experimental procedure to an accepted treatment for end-stage liver disease. Yet, many potential recipients will die from infection, coagulopathy, or metabolic derangements before a donor liver becomes available. In addition, primary graft dysfunction after transplantation still represents a significant drain on professional resources. For these reasons, more attention is being directed toward identification of nutritional and metabolic factors in both the liver recipient and organ donor that can influence transplant outcome. The metabolic alterations present in these patients before and after liver transplantation require a more sophisticated approach to the provision of appropriate nutrition support. The goals of nutrition intervention for both the recipient and donor are to foster improved function of the allograft liver and to optimize eventual transplant outcome.

Iron dextran was introduced more than 30 yr ago for the parenteral treatment of iron deficiency anemia that is refractory to oral therapy. Iron dextran is a preparation of ferric hydroxide complexed with a low molecular weight fraction of dextran. Iron deficiency anemia is one of the most common nutritional deficiency diseases and occurs worldwide secondary to inadequate dietary iron, usually with excessive gastrointestinal blood losses. Repletion of iron stores is often complicated by intolerance to oral iron supplementation and may require parenteral iron. Parenteral iron can be administered via the intramuscular or intravenous route either directly or as an additive to total parenteral nutrition. Both routes of administration can cause various side effects and a test dose is recommended before therapeutic administration to assess the risk for anaphylaxis. Although the efficacy and safety of parenteral iron dextran have been convincingly demonstrated, supplementation may be contraindicated in the setting of infection.

The recently completed Diabetes Control and Complications Trial (DCCT) provided compelling evidence that intensive treatment of people with insulin-dependent diabetes mellitus can delay or prevent diabetic microvascular complications. Although not studied in the DCCT, patients with noninsulin-dependent diabetes mellitus likely will benefit from near-normoglycemia. Although it is difficult to prove a similar causal relation between hyperglycemia and infection (this outcome was not looked for in the DCCT), there is substantial in vitro data and evolving clinical studies that support this hypothesis. This information is presented in this article following a review of the regulation of glucose levels.

This document was prepared by the Committee on Clinical Practice Issues in Health and Disease of The American Society for Clinical Nutrition (ASCN). The committee recommends that each major medical center has at least one physician nutrition specialist (PNS) who will be a regional resource for complex nutrition cases and will have a leadership role in the provision of coordinated nutrition services. The PNS will be responsible for nutrition education programs in associated schools of medicine and will be a role model for aspiring physicians. Typically, these individuals will have thorough training in human nutrition research. The PNS should be supported by a unique combination of resources including clinical earnings, teaching hospital and school of medicine salaries, state and federal funds, as well as private sector support. The ASCN should take a leadership role in developing the national identity of the PNS and in achieving recognition of board certification in nutrition.

Proliferating cell nuclear antigen (PCNA), an auxiliary protein of DNA polymerase-delta, has recently been proposed as a marker of proliferation that is detectable in formalin-fixed paraffin-embedded tissue. Fixation time has been known to influence protein immunoreactivity and therefore can significantly influence the results of a quantitative immunohistochemical assay. In this study, we investigate the relationship between formalin fixation time and immunoreactivity for PCNA in paraffin-embedded sections and examine the effect of postfixation tissue treatment with modified Bouin's solution. Samples of small and large intestine from two freshly sacrificed rats were fixed in 10% buffered formalin for 6, 30, 54, 174, 340, and 508 h. Standard histological processing was performed on paired specimens whose treatment differed only by predehydration immersion in a picric acid and mercuric chloride-containing solution. Paraffin sections were reacted with monoclonal antibody PC10 in a standard immunoperoxidase assay. Staining intensity for PCNA was scored on a scale of 0 to 10, and the mean number of PCNA-positive cells per crypt (10 crypts counted) was determined. No difference between animals was found. PCNA immunoreactivity was maximal in specimens fixed for 6 to 30 h, exponentially declining with longer fixation time. The rate of decline was mitigated in the treated sections. Fixation-time dependence of PCNA immunoreactivity has immediate implications for intra- and interlaboratory comparisons, especially in experimental studies in which specimens can be stored in formalin for variable times followed by batch processing. With regard to surgical pathology specimens, this study suggests that sample comparisons are valid, since routine fixation time is within the optimal rage for PCNA immunodetection.

To assess the usefulness of mid-upper arm circumference (MUAC) as a substitute for body mass index (BMI: kg/m2) or an additional measure of adult nutritional state.Variously sampled adults aged 18-60 years from selected regions of five African countries, India, China and Papua New Guinea were measured.2421 men and 3248 women were measured for their heights, weights and MUAC. Of these, 1569 men and 1905 women also had their triceps skinfold thickness measured, thus allowing additional estimates of muscle area circumferences and fat areas in the arm.MUAC and BMI were highly correlated in each national group; each group's MUAC differed from the overall mean MUAC at any BMI value by10%. Women's MUACs were smaller than men's at equivalent BMIs. Increases in MUAC with age were statistically significant but trivial. Muscle and fat measurements showed similar increases with BMI; a larger muscle mass in men explained their greater MUACs but muscle differences alone did not explain national variations in MUAC. The -1 SD MUAC value, taken as an independent measure of peripheral tissue wasting, readily distinguished those with a BMI16.0 from those with a BMI18.5; intermediate grades of BMI were poorly specified by MUAC values.MUAC values of 23.0 cm in men and 22.0 cm in women are useful cut-off points for simple screening of nutritional state. In combination with BMI it may provide a more refined classification of CED. This new combined classification scheme may be a better means of discriminating the at-risk underweight adults from those who are thin but not at risk.

Sprague-Dawley rats, subcutaneously inoculated with Walker 256 carcinosarcoma, were injected intraperitoneally with recombinant human TNF-alpha at a dose of 4.75 x 10(6) U/kg for 3 consecutive days. Protein metabolism and cell-cycle kinetics of the tumor were studied. The results showed a significant decrease in tumor volume and weight in comparison with control. TNF resulted in significant decrease in tumor protein fractional synthesis rate (25.3% +/- 3.5%.d-1 versus control 42.9% +/- 2.7%.d-1, P0.01), protein synthesis (0.20 +/- 0.05 g/d versus control 1.14 +/- 0.20 g/d, P0.001) and fractional growth rate (24.3% +/- 2.1%.d-1 versus control 35.8% +/- 2.3%.d-1, P0.01), but no change of tumor protein fractional degradation rate. TNF also resulted in remarkable decline in labelling index (30.8% +/- 4.2% versus control 44.7% +/- 4.2%, P0.01) and G1 phase increase (6.0% +/- 1.3% versus control 12.2% +/- 2.5%, P0.01) of tumor cells, 6 hours after injection of bromodeoxyuridine, by flow cytometry. The results indicate that TNF inhibits tumor growth as a result of decreases in tumor cell DNA and protein syntheses.

Total parenteral nutrition (TPN) has been a major advance in patient therapeutics, particularly for critically ill patients. Incorrect administration of TPN, however, primarily through excessive use of energy, either as dextrose or lipid, is an underappreciated risk factor that leads to serious complications in nutritional support. Even a modest degree of uncontrolled hyperglycemia induced by TPN appears to increase the risk of infection, usually to a level that can nullify any potential benefit of feeding. Rapid and/or excessive lipid administration can interfere with the reticuloendothelial system function, which may also predispose the patient to serious infection. The goals of nutritional support in the critically ill are to provide ample protein at 1.5 to 2.0 g/kg body weight/day, while limiting calories to approximately the patient's resting energy expenditure, which optimally supports the metabolic response to injury. Repleting the critically ill, malnourished patient with calories in excess of the patient's energy expenditure is not effective, but rather increases the likelihood of an adverse outcome.

A midarm muscle circumference (AMC)10th percentile indicates severe protein-energy malnutrition. We identified 20 consecutive patients receiving specialized nutritional therapy from the Nutrition Support Service of the New England Deaconess Hospital during a 3-mo period who had AMC10th percentile and 24-h urine and serum creatinine determinations performed. Mean weight was 96 +/- 25% of ideal body weight (IBW), with only 7 patients85% IBW, reaffirming that weight is often insensitive for the identification of lean tissue loss. Twenty-four-hour urine creatinine excretion confirmed most to be severely lean body mass depleted (creatinine-height index60% in 17 subjects) as predicted by AMC. Sixteen patients had normal kidney function as assessed by serum creatinine levels and hospital norms (0.3-1.2 mg/dl). However, abnormal creatinine clearances were found in 15 of 20 subjects (normal 80-100 ml/min), with a mean value (53 +/- 23 ml/min) also below normal. These results suggest that the usual normal range for serum creatinine, based on well-nourished patients, should be adjusted in severely malnourished patients. Considering the upper limit of normal serum creatinine in this population to be 0.7 mg/dl, to reflect the approximately 60% reduction in lean tissue indicated by an AMCor = 10th percentile, would identify all but 1 patient with an abnormal creatinine clearance (sensitivity 93%, specificity 67%). Use of a predictive formula (the Cockcroft-Gault equation) also identified those with kidney dysfunction but overestimated actual function to a level not usually requiring drug dose adjustment and did not obviate the need for further testing.(ABSTRACT TRUNCATED AT 250 WORDS)

Nutrition assessment and therapy in end-stage liver disease has become increasingly important with the advent of orthotopic liver transplantation. Reduced lean body mass, increased risk of sepsis, and altered metabolism of carbohydrates, protein, and fat are characteristic of patients with liver dysfunction. This study assesses the prevalence of protein-calorie malnutrition and the relative utility of various parameters used to define protein-calorie malnutrition in 104 patients before liver transplantation. Five subgroups were identified for analysis: primary biliary cirrhosis (PBC, n = 21), sclerosing cholangitis (SC, n = 12), chronic active hepatitis (CAH,n = 34), acute hepatitis (AH,n = 11), and other liver diseases (OD,n = 26). Clinical characteristics, anthropometric measurements, secretory protein levels, 24-h urinary creatinine and urea nitrogen, and immunological studies were assessed. Significant differences between groups were noted in age, height, weight, and percentage ideal body weight (IBW), but no differences were noted with respect to triceps skin fold (TSF) and arm muscle circumference (AMC), where uniform depletion of fat and protein stores was found. Overall percentage IBW was significantly elevated (112 +/- 20, mean +/- SD, p0.001), whereas TSF and AMC percentage standards were 71 +/- 33 and 89 +/- 11% (respective p0.001). With the5th percentile of TSF and AMC as markers of malnutrition, 33 and 43% of patients were malnourished, respectively. Hepatic synthetic function was impaired in all groups, with overall albumin 25 +/- 0.6 g/L, transferrin 1.60 +/- 0.66 g/L, and prothrombin 16.8 +/- 6.2 s.(ABSTRACT TRUNCATED AT 250 WORDS)

Current research suggests that a diet high in fish oil may be useful for immunomodulation in hospitalized patients. However, one of the side effects of fish oil is a prolongation of the bleeding time, specifically by reducing platelet aggregability. Although this effect might be beneficial for patients with cardiovascular disease, it would be a potential concern in certain critically ill patients. To address this concern, we conducted a prospective study of platelet aggregation in 16 surgical patients who were randomly assigned to receive either a diet containing 16.5 g of fish oil in 1500 ml (Impact) or usual care (standard enteral formulas devoid of fish oil). Feeding was successfully accomplished in the patient group receiving a diet that provided approximately 14.2 g of fish oil/day for 1 wk without significantly affecting platelet aggregability. Thus, it appears that, over the short term, this dose of fish oil does not alter platelet function in hospitalized surgical patients.

The incidence of pancreatitis after cardiopulmonary bypass is reported as0.1%. We report a milder form of pancreatitis characterized by hyperlipasemia and early intolerance to enteral nutrition without overt signs of clinical pancreatitis. A retrospective study was conducted in 72 patients who had received tube feeding. A statistically (p = 0.01) greater incidence of symptomatic hyperlipasemia was noted in post-cardiopulmonary bypass (PCPB) patients (42%, 5 of 12) than in non-PCPB patients (0%, 0 of 60). Four of the 5 PCPB patients who developed symptomatic hyperlipasemia received tube feeding into the stomach or duodenum before onset of their symptoms. The overall incidence of PCPB symptomatic hyperlipasemia during the study period was 1.3% (5 of 375). A prospective study was then carried out in 54 PCPB patients. Five patients became critically ill, and 4 of these developed symptomatic hyperlipasemia. Three of the 4 patients had received tube feeding into the stomach or duodenum before the onset of symptoms. In all cases, the symptoms of tube-feeding intolerance were mild and resolved with termination of feeding. This study suggests that critically ill cardiopulmonary bypass patients may be more susceptible to developing symptomatic hyperlipasemia, which is characterized by early intolerance to enteral nutritional support.

This study assessed the effects of total parenteral nutrition (TPN) containing long-chain triglycerides (LCTs), an equimolar physical mixture of LCT and medium-chain triglycerides (MCTs), and a structured triglyceride synthesized from equimolar amounts of MCT and LCT on energy and protein metabolism after thermal injury (25% body surface area full-thickness scald burn). Male Sprague-Dawley rats (245-271 g) received isovolemic diets intravenously that supplied 250 kcal.kg-1.day-1, 2 g amino acid nitrogen.kg-1.day-1, and 50% of nonprotein calories as lipid and 50% as dextrose for 3 days. Whole-body and tissue leucine kinetics were estimated by a 4-h continuous infusion of L-[1-14C]leucine on day 3. Nitrogen balance, plasma albumin, plasma glucose, energy expenditure, and whole-body and liver and rectus muscle protein kinetic parameters were determined. No significant differences were noted in any of the parameters measured. This study suggests that the unique protein-sparing actions usually associated with structured triglyceride administration are not seen when they are provided as 50% of nonprotein calories. In addition, the ratio of MCT to LCT in the starting mixture from which the structured triglycerides are synthesized may be an important determinant of the protein-sparing actions attributed to these lipids.

Tolerance of elemental (for example, Peptamen [PEP]) or free amino acid (for example, Vivonex TEN [VIV]) tube feeding diets is controversial, especially in the critically ill patient who is hypoalbuminemic. A prospective, randomized trial was conducted to compare differences between feeding PEP (n = 8) or VIV (n = 8) in critically ill, elderly (average age of 66 years) patients. Diets were administered through nasogastric or postpyloric feeding tubes. Eleven patients had diseases of the gastrointestinal tract; all underwent surgical treatment. Patients were fed each diet at full strength, beginning with 20 to 30 milliliters per hour and advancing by 10 to 20 milliliters every day until goal rate was reached, usually on day 4. Assessment was made for ability to comply with rate of tube feeding ordered, compliance with caloric goal and tolerance (as evidenced by abdominal discomfort and diarrhea). Diarrhea was qualitatively defined as more than three stools per day and then quantitatively as the mean number of stools daily. There were no significant differences between the two groups in terms of compliance with prescribed tube feeding order or caloric goal or the presence of diarrhea and abdominal discomfort. There was a significant difference between the two groups in terms of the actual number of stools per day (PEP equals 1.38 versus VIV equals 2.25, p less than 0.02). Serum albumin concentrations upon initiation of the diets were 2.3 grams per deciliter in both groups. We conclude that tolerance to the two diets were similar because it was possible to feed enterally either PEP or VIV in critically ill, hypoalbuminemic patients (serum albumin concentrations of less than 2.5 grams per deciliter) successfully, irrespective of diet. Although there were more stools in the VIV group, this did not reduce compliance with the goals.

The metabolic effects of total parenteral nutrition (TPN) solutions containing different profiles of individual amino acids were investigated in the rats bearing Walker 256 carcinosarcoma. The rats were subcutaneously inoculated with 10(7) tumor cells and 6 days later were continuously infused intravenously for 8 days with three different TPN solutions. The experimental and control solutions were composed of high concentrations of branched chain amino acids (BCAA) and arginine (high Arg + BCAA TPN), high concentrations of BCAA (high BCAA TPN) and regular amino acids (regular TPN), respectively, and were isonitrogenous, isocaloric, and isovolemic. Rats receiving subcutaneous injection of saline rather than tumor cells received high Arg + BCAA TPN as pair-fed controls. The flooding dose method of 14C-leucine was used for the analysis of protein synthesis. With the feeding of high Arg + BCAA TPN, the tumor-bearing rats revealed a smaller increase of tumor volume and lower tumor fractional rates of growth (Kg) and synthesis (Ks) as well as protein synthesis (PS), compared with the high BCAA TPN and regular TPN in tumor-bearing rats. There were no significant differences of Ks and PS in liver and muscle between TPN groups, whereas tumor-bearing rats infused with high Arg + BCAA TPN displayed higher levels of whole-body Ks and PS than other TPN groups in tumor-bearing rats and pair-fed nontumorous rats. Except for liver RNA content which showed a lower level in tumor-bearing rats with high Arg + BCAA TPN, no other differences of DNA and RNA contents were found in tumor, liver, and muscle of the different TPN groups. The current results indicate that individual amino acids can influence tumor growth and protein metabolism, and that arginine, in combination with BCAA, may reduce tumor growth through a reduction in protein synthesis.

A recent study demonstrated that the incidence of new arrhythmias occurring during central venous catheter insertion or exchange was 41% atrial and 25% ventricular arrhythmias (12% couplets or greater). Over-insertion of the guidewire, causing direct stimulation to the right side of the heart, has been postulated to be the causative factor. A new technique that allows the operator to control the length of guidewire inserted was developed. With this technique on a population of hospitalized patients, similar to those in the previous study, the incidence of atrial arrhythmias decreased to 32% and the incidence of ventricular arrhythmias to 6% (single premature ventricular contractions only). Although this new technique has limitations, there was a dramatic improvement in the incidence of cardiac arrhythmias. These results indicate a need for modifications in the available equipment to avoid the infrequent but life-threatening complication of malignant arrhythmia.

Obesity is associated with many comorbid disease states including neoplasia. The increased risk of developing endometrial cancer is thought to be due to the higher level of circulating estrogens in obese women. Uterine leiomyomata (fibroids) are also thought to be influenced by estrogens. To determine whether patients presenting with symptomatic uterine fibroids were more obese than the general population, we retrospectively reviewed the hospital records of 144 women who underwent either hysterectomy or myomectomy for uterine fibroids. Obesity was defined as preoperative weight greater than 120% of desirable body weight (DBW) for the patient's height. In our investigation, 51% of the study population were obese. Moreover, 16% were severely obese (defined as greater than 150% DBW). When compared with the general population of women in the United States matched for height and age, the study population was significantly heavier. (p less than 0.0002). Patient age, parity, menopausal status, and degree of obesity did not correlate with the number of fibroids within the uterus. Fibroid size was significantly larger in nulliparous women (p less than 0.005). These results suggest that symptomatic uterine fibroids may be another comorbid disease state associated with obesity.

Essential amino acids, found in abundance in high-quality dietary protein, are required daily by hospitalized patients and healthy persons to maintain the dynamic process of protein metabolism. One method for assessing dietary protein quality is by determining a diet's chemical score, ie, the ratio of a gram of the limiting amino acid in a test diet to the same amount of the corresponding amino acid in a reference diet (eg, whole-egg protein) multiplied by 100. This investigation used the chemical score to evaluate the protein quality of 9 parenteral and 17 enteral diets commonly used to feed hospitalized patients. Standard parenteral and enteral products (ie, formulas that had not been designed for patients with a specific disease state) had chemical scores that ranged from 46% to 70%. Limiting amino acids were either methionine (plus cysteine) or phenylalanine (plus tyrosine). Products designed for patients with renal failure had the highest scores, which ranged from 85% to 145%. Products that were enriched with branched-chain amino acids for trauma patients had scores that ranged from 38% to 73%. The only product available for patients with pulmonary compromise had a score of 50%. The lowest scores, which ranged from 5% to 13%, were found in products for patients with hepatic failure. All products, except those with chemical scores below 13%, may be fed in relatively small amounts of protein (7 to 33 g) to satisfy the minimum daily requirements of essential amino acids, although such levels would not meet minimal daily nitrogen requirements. We recommend that dietitians use the chemical score to assess the protein quality of parenteral and enteral diets.

Bacterial translocation across the bowel wall has recently been proposed as a major problem in the stressed patient. Consequently, there has been considerable interest in fostering bowel wall integrity as a barrier to bacteria and endotoxin. One postulated means to promote this barrier function has been through the provision of the preferred fuels of the bowel wall. Among these are the short-chain fatty acids (SCFAs) which are found to a limited extent in the diet but are primarily produced through the fermentation of non-digestible carbohydrates by the bacterial flora of the colon. In both animal and human studies, SCFAs have been shown to stimulate intestinal mucosal growth. Because non-digestible carbohydrates, after colonic fermentation, are precursors to SCFAs, similar effects to those found with direct provision of SCFAs may be anticipated. Pectin, beta-glucan, and lactulose are among the many available nonabsorbable carbohydrates that could serve as a source of these trophic stimulants to colonic mucosa. Short-chain fatty acids and their precursors deserve extensive and clinical evaluation to define their ultimate role in human disease.

This article reviews current investigations of the use of alternative lipid sources to enhance the metabolic and immune functions of hospitalized patients. Conventional lipids have been implicated as the cause of a variety of iatrogenic side effects in critically ill hospitalized patients, and long-chain triglycerides of the omega-6 family have been shown to be potentially detrimental to immune function. Alternative lipids (fish oils, medium-chain triglycerides, and structured triglycerides) have been proposed as substitutes for conventional long-chain, polyunsaturated omega-6 fatty acids. Unlike long-chain triglycerides, medium-chain triglycerides are more rapidly cleared from the blood and are completely oxidized for energy. However, medium-chain triglycerides contain no essential fatty acids. On the other hand, structured triglycerides offer the advantages of long-chain triglycerides (essential fatty acids) and of medium-chain triglycerides (rapid clearance and oxidation). Fish oils, which contain long-chain polyunsaturated omega-3 fatty acids, appear to be anti-inflammatory and to affect immune function differently from the omega-6 long-chain triglycerides.

Previous studies suggest that continuous or intermittent cimetidine infusion provides a stable and sustained therapeutic blood concentration that maintains a gastric pH greater than 4.0. Twenty-seven patients receiving cimetidine were randomized to one of five treatments. Groups 1 and 2 were given cimetidine intermittently, whereas Groups 3, 4, and 5 received the drug continuously via a total parenteral nutrient (TPN) admixture. Group 1 was given 300 mg every 8 hours, and Group 2 received 300 mg every six hours. Groups 3, 4, and 5 received 600, 900, and 1200 mg per day, respectively, as a continuous infusion in the TPN admixture. Forty-eight individually prescribed TPN admixtures were used to deliver cimetidine continuously; 23 were composed of amino acids and glucose as base nutrients, whereas 25 contained amino acids, glucose, and lipids (3-in-1 or total nutrient admixtures). Serum levels of cimetidine were measured six times in 40 h (Group 1) or 42 h (Group 2-5). A two-way analysis of variance (ANOVA) revealed statistically significant differences in the serum cimetidine concentrations between groups (p less than 0.0001), but not with respect to time interval (p = 0.8687). No significant differences were noted in mean serum cimetidine concentrations between Groups 2 and 3, despite employing half the total dose in Group 3. Equivalent daily dosages were then stratified as the percentage of subtherapeutic (less than 500 ng/ml), therapeutic (500-1250 ng/ml), and supratherapeutic (greater than 1250 ng/ml) values.(ABSTRACT TRUNCATED AT 250 WORDS)

During the course of a critical illness, many patients become ventilator dependent. The standard assessment criteria are not always accurate in predicting potential for extubation. This investigation was designed to analyze whether the work of breathing (WOB) was a more reliable predictor of ventilator dependence. Twenty consecutive ventilator-dependent patients were prospectively studied. Nineteen required ventilator support for greater than 2 wk and all were considered ventilator dependent because of their inability to tolerate weaning trials. The oxygen consumption (VO2) and resting energy expenditure were measured using a metabolic gas monitor. Respiratory mechanics and arterial blood gas measurements were obtained, and the deadspace to tidal volume ratio (VD/VT) was calculated. The WOB was determined by the difference in VO2 between spontaneous and mechanical ventilation, and expressed as a percentage of VO2 during mechanical ventilation. Five of eight patients with a WOB less than 15% (mean 1.9) were extubated within 2 wk of study, while none of 12 patients with a WOB greater than or equal to 15% (mean 34) were able to be extubated in this period. The differences in the WOB between the two groups were statistically significant (p less than .01), while there was no significant difference in mechanics, PaCO2, VD/VT or measured resting energy expenditure. These data support the use of WOB determinations in evaluating extubation potential. Using a reference value for the WOB of 15%, this study had a sensitivity of 100% and a specificity of 80%. This proved to be of greater predictive value than traditional criteria.

The in vivo rates of protein synthesis were assessed in tumor tissue, skeletal muscle, and whole body of rats bearing the Walker 256 carcinosarcoma. Estimates of protein synthesis in the nontumorous tissues were compared to tumor-free controls. Changes in size of the whole animal and tumor (i.e., growth) were measured, and fractional rates of growth, synthesis, and breakdown were estimated. Muscle protein synthesis and whole-body growth were significantly reduced in rats bearing larger tumors, and both were negatively correlated with tumor size (r = -0.723 and -0.825, respectively; P less than 0.01). Furthermore, whole-body and muscle protein synthesis were positively correlated with body growth (r = 0.380 and 0.563, respectively; P less than 0.05). Tumor growth followed first-order kinetics between days 7 and 13 following implantation, with a mean rate constant of 34.3%/day for the larger tumors and 27.7%/day for the small tumors. The difference in tumor growth became statistically significant over the final 3 days of tumor volume measurements. Fractional protein synthesis was significantly lower in the larger compared to the smaller tumors (48.6 versus 84.8%/day; P less than 0.05) as measured on day 14. This finding indicates a lower protein breakdown rate for the larger tumors (14.3 versus 59.0%/day; P less than 0.01) and suggests that the process of protein breakdown could play a significant role in determining tumor size, leading support to the theory of tumors acting as nitrogen traps.

Thirty-six obese adults received a protein-sparing modified fast (PSMF) consisting of 1.5 g of meat protein per kilogram of ideal body weight and meeting vitamin, mineral, and fluid requirements. These studies were conducted as short-term inpatient metabolic studies followed by a program of outpatient obesity treatment. Thirty-one patients were contacted from one to 4 1/2 years from initial assessment. Significant weight loss of greater than 9 kg (20 lb) occurred in more than half the patients, and of greater than 40 lb in one-third of patients over the study period. A PSMF for weight reduction, accompanied by instruction in behaviour modification, nutrition, and exercise for maintenance of weight loss may be helpful in the management of obesity.

Branched chain amino acids were administered intragastrically in a septic-fractured rat model to determine the degree and mechanism of their protein-sparing ability. The septic injury model was first shown to produce a metabolic response characterized by hyperglycemia, reduced ketonemia and increased nitrogen loss. Branched chain amino acids were then administered either alone or as 25% or 50% (w/w) of a complete crystalline amino acid solution. L-(U-14C)-tyrosine was added to the diet to estimate protein synthesis in individual tissues. Branched chain amino acids, when given alone, spared total body nitrogen as compared with fasting by increasing the fractional synthesis of both mixed liver and muscle protein. Although the two complete amino acid mixtures produced similar nitrogen preservation and muscle synthesis in the septic animals, the crystalline amino acid diet containing 50% branched chain amino acids resulted in the greatest preservation of total liver nitrogen and the highest fractional synthetic rate. The effect of branched chain amino acids would not appear to be explained by their nitrogen content alone, and in starvation with injury and infection, increased intakes may have potential benefit. Clinical trials in starved, injured man appear to be indicated.