Assessment of the gut bacterial microbiome and metabolome of girls and women with Rett Syndrome.

BACKGROUND: Gastrointestinal problems affect the health and quality of life of individuals with Rett syndrome (RTT) and pose a medical hardship for their caregivers. We hypothesized that the variability in the RTT phenotype contributes to the dysbiosis of the gut microbiome and metabolome in RTT, predisposing these individuals to gastrointestinal dysfunction. OBJECTIVES: We characterized the gut bacterial microbiome and metabolome in girls and young women with RTT (n = 44) and unaffected controls (n = 21), and examined the relation between the composition of the microbiome and variations in the RTT phenotype. METHODS: Demographics and clinical information, including growth and anthropometric measurements, pubertal status, symptoms, clinical severity score, bowel movement, medication use, and dietary intakes were collected from the participants. Fecal samples were collected for analysis of the gut microbiome using Illumina MiSeq-based next-generation sequencing of the 16S rRNA gene followed by bioinformatics analysis of microbial composition, diversity, and community structure. Selected end-products of microbial protein metabolism were characterized by liquid chromatography-mass spectrometry. RESULTS: The gut bacterial microbiome differed within the RTT cohort based on pubertal status (p<0.02) and clinical severity scores (p<0.02) of the individuals and the type of diet (p<0.01) consumed. Although the composition of the gut microbiome did not differ between RTT and unaffected individuals, concentrations of protein end-products of the gut bacterial metabolome, including γ-aminobutyric acid (GABA) (p<0.001), tyrosine (p<0.02), and glutamate (p<0.06), were lower in the RTT cohort. Differences in the microbiome within RTT groups, based on symptomatic anxiety, hyperventilation, abdominal distention, or changes in stool frequency and consistency, were not detected. CONCLUSIONS: Although variability in the RTT phenotype contributes to the dysbiosis of the gut microbiome, we presently cannot infer causality between gut bacterial dysbiosis and gastrointestinal dysfunction. Nevertheless, alterations in the gut metabolome may provide clues to the pathophysiology of gastrointestinal problems in RTT.

MANAGEMENT OF ENDOCRINE DISEASE: Morbidity in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine condition in premenopausal women. The syndrome is characterized by hyperandrogenism, irregular menses and polycystic ovaries when other etiologies are excluded. Obesity, insulin resistance and low vitamin D levels are present in more than 50% patients with PCOS, these factors along with hyperandrogenism could have adverse effects on long-term health. Hyperinflammation and impaired epithelial function were reported to a larger extent in women with PCOS and could particularly be associated with hyperandrogenism, obesity and insulin resistance. Available data from register-based and data linkage studies support that metabolic-vascular and thyroid diseases, asthma, migraine, depression and cancer are diagnosed more frequently in PCOS, whereas fracture risk is decreased. Drug prescriptions are significantly more common in PCOS than controls within all diagnose categories including antibiotics. The causal relationship between PCOS and autoimmune disease represents an interesting new area of research. PCOS is a lifelong condition and long-term morbidity could be worsened by obesity, sedentary way of life, Western-style diet and smoking, whereas lifestyle intervention including weight loss may partly or fully resolve the symptoms of PCOS and could improve the long-term prognosis. In this review, the possible implications of increased morbidity for the clinical and biochemical evaluation of patients with PCOS at diagnosis and follow-up is further discussed along with possible modifying effects of medical treatment.

Mesenchymal stromal cell-based therapy: Regulatory and translational aspects in gastroenterology.

The past decade has witnessed an outstanding scientific production focused towards the possible clinical applications of mesenchymal stromal cells (MSCs) in autoimmune and chronic inflammatory diseases. This raised the need of novel standards to adequately address quality, efficacy and safety issues of this advanced therapy. The development of a streamlined regulation is currently hampered by the complexity of analyzing dynamic biological entities rather than chemicals. Although numerous pieces of evidence show efficacy in reducing intestinal inflammation, some inconsistencies between the mechanisms of action of rodent vs human MSCs suggest caution before assigning translational value to preclinical studies. Preliminary evidence from clinical trials showed efficacy of MSCs in the treatment of fistulizing Crohn's disease (CD), and preparations of heterologous MSCs for CD treatment are currently tested in ongoing clinical trials. However, safety issues, especially in long-term treatment, still require solid clinical data. In this regard, standardized guidelines for appropriate dosing and methods of infusion could enhance the likelihood to predict more accurately the number of responders and the duration of remission periods. In addition, elucidating MSC mechanisms of action could lead to novel and more reliable formulations such as those derived from the MSCs themselves (e.g., supernatants).

Radioprotective potential of Lagenaria siceraria extract against radiation-induced gastrointestinal injury.

The cucurbits (prebiotics) were investigated as novel agents for radio-modification against gastrointestinal injury. The cell-cycle fractions and DNA damage were monitored in HCT-15 cells. A cucurbit extract was added to culture medium 2 h before irradiation (6 Gy) and was substituted by fresh medium at 4 h post-irradiation. The whole extract of the fruits of Lagenaria siceraria, Luffa cylindrica, or Cucurbita pepo extract enhanced G2 fractions (42%, 34%, and 37%, respectively) as compared with control (20%) and irradiated control (31%). With cucurbits, the comet tail length remained shorter (L. siceraria, 28 µm; L. cylindrica, 34.2 µm; C. pepo, 36.75 µm) than irradiated control (41.75 µm). For in vivo studies, L. siceraria extract (2 mg/kg body weight) was administered orally to mice at 2 h before and 4 and 24 h after whole-body irradiation (10 Gy). L. siceraria treatment restored the glutathione contents to 48.8 µmol/gm as compared with control (27.6 µmol/gm) and irradiated control (19.6 µmol/gm). Irradiation reduced the villi height from 379 to 350 µm and width from 54 to 27 µm. L. siceraria administration countered the radiation effects (length, 366 µm; width, 30 µm, respectively) and improved the villi morphology and tight junction integrity. This study reveals the therapeutic potential of cucurbits against radiation-induced gastrointestinal injury.

The Cost of Gastrointestinal Adverse Events and the Impact of Dose-Reductions/Discontinuations on Acute Rejection in Kidney Transplant Patients of Mycophenolate Mofetil-Related Compared to Enteric-Coated Mycophenolate Sodium: A Pharmacoeconomic Study.

BACKGROUND: Mycophenolate mofetil (MMF) is effective in decreasing rejection and graft loss in renal transplant patients. Enteric-coated mycophenolate sodium (EC-MPS) was designed to reduce MMF gastrointestinal (GI) effects. Dose manipulations in MMF/EC-MPS produce GI tolerability, increasing the risk of rejection. Significant differences in tolerance of MMF/EC-MPS may have economic influence in transplant efficacy outcomes. Herein, we performed a pharmacoeconomic evaluation of acute rejection incidence and interventions in GI-intolerant patients using MMF/EC-MPS. METHODS: A cost-effectiveness analysis was performed through a decision tree model with a 1-year time horizon estimating costs and effectiveness of MMF and EC-MPS in renal transplant patients with GI intolerance. The costs and use of resources (US dollars; USD) were from payer perspective (Mexican Social Security). Primary health outcomes were mean cost of acute rejection and GI adverse events treatment. A probabilistic sensitivity analysis (PSA) was generated to test robustness of the model. RESULTS: Calculated incidence of MMF GI intolerance was 44%, and calculated rejection incidence for MMF was 24.05%. Calculated incidence of EC-MPS GI intolerance was 29%, and calculated rejection incidence for EC-MPS was 20.1% Total cost of MMF with GI intolerance during 1-year period plus cost of treating one rejection sums $752,107.25 USD. Total cost of EC-MPS with GI intolerance plus cost of treating one rejection sums $638,018.97 USD. CONCLUSION: EC-MPS-based treatment is a cost-saving alternative vs MMF in GI-intolerant kidney transplant patients. PSA supports the decision to utilize EC-MPS based on cost-effectiveness analysis.

Lead Assessment in Biological Samples of Children with Different Gastrointestinal Disorders.

Lead (Pb) levels have been evaluated in the biological samples of children with different gastrointestinal disorders. Blood, scalp hair, and urine samples of children (of age 4-10 years) complaining about different gastrointestinal disorders were analyzed. For comparison, age matched healthy subjects were also included in this study. Biological samples were digested in a microwave oven prior to Pb determination by graphite furnace atomic absorption spectrometry. Significant differences in Pb profile were found between the diseased and referent children. Elevated Pb contents were observed in case of diseased children than WHO permissible limit, while normal results were obtained for healthy referents. The results were compared with those of healthy children having the same age, socioeconomic status, and residential areas.

A clinicopathologic study of 24 cases of systemic mastocytosis involving the gastrointestinal tract and assessment of mucosal mast cell density in irritable bowel syndrome and asymptomatic patients.

Counting mast cells in gastrointestinal (GI) mucosal biopsies is becoming an increasingly common practice. The primary reason for this exercise is to evaluate for possible involvement by systemic mastocytosis (SM). However, the features of mastocytosis in GI biopsies are not well described. In addition, recent studies have suggested that increased mast cells may be involved in the pathogenesis of some cases of diarrhea-predominant irritable bowel syndrome (IBS); the term "mastocytic enterocolitis" has been proposed for such cases. As the baseline mast cell density in colonic biopsies from normal patients has not been established in large cohorts, there is no widely accepted threshold for what constitutes increased mucosal mast cells. The aims of this study were (1) to determine the utility of GI biopsies for the diagnosis of SM, (2) to characterize the clinical, histologic, and immunohistochemical features of mastocytosis in the GI tract, (3) to determine mast cell density in normal colonic mucosa from a large cohort of asymptomatic patients, and (4) to compare these findings with those from patients with diarrhea-predominant IBS. Twenty-four patients with SM involving the GI tract, 100 asymptomatic patients, and 100 patients with IBS (the latter 2 groups with histologically normal colonic biopsies) were included. For the mastocytosis group, 107 biopsies (70 involved by mastocytosis; 67 mucosal, 3 liver) from 20 women and 4 men were evaluated (median age 59 y). The most commonly involved site was the colon (19 patients, 95%), followed by ileum (86%), duodenum (80%), and stomach (54%). In 16 cases (67%), the first diagnosis of SM was made on the basis of GI biopsies. Seventeen patients had documented cutaneous mastocytosis. Fifteen of 17 patients who underwent bone marrow biopsy had marrow involvement by SM. Eighteen patients had indolent disease, and 6 had aggressive disease (including all 3 with liver involvement). The most common GI symptom was diarrhea, followed by abdominal pain, nausea, weight loss, bloating, vomiting, or reflux. Liver disease presented with hepatomegaly and ascites. Endoscopic abnormalities (observed in 62%) included erythema, granularity, and nodules. Histologically, involved biopsies were characterized by infiltrates of ovoid to spindle-shaped mast cells in aggregates or sheets in the lamina propria, sometimes forming a confluent band underneath the surface epithelium; 25% of biopsies had only focal involvement (single aggregate). Prominent eosinophils were seen in 44% of involved colonic/ileal biopsies and 16% of duodenal biopsies. Mast cells were highlighted by diffuse membranous staining for KIT and CD25. In the nonmastocytosis groups, all biopsies contained singly dispersed mast cells with no aggregates. The mean highest mast cell counts (in a single high-power field) for asymptomatic patients and IBS patients were 26 (range, 11 to 55) and 30 (range, 13 to 59), respectively. In summary, GI (especially colonic) biopsies can establish a diagnosis of SM in patients with GI symptoms. GI involvement is usually subtle and is often associated with prominent eosinophils, which may obscure the mast cell infiltrate. KIT and CD25 are invaluable markers for the diagnosis. Mast cell density in colonic mucosa from asymptomatic patients is highly variable. Although patients with diarrhea-predominant IBS on average have mildly increased mast cells, the overlap in range with that of control patients is too great for this difference to be clinically useful. These findings argue against the utility of counting GI mucosal mast cell in patients with chronic diarrhea.

Breath tests for the assessment of the orocecal transit time.

Orocecal transit time (OCTT) is one of the main determinant of the hunger ratings and gastrointestinal sensitivity. While marked-isotopes scintigraphy is the gold standard in its determination in the clinical frame, breath tests are cheap, well-tolerated and non-invasive alternatives. In fact C-13 and C-14 stable isotopes breath tests can be used to assess gastric emptying and OCTT in the clinical and research frames. Moreover, hydrogen (H2) lactulose breath test can be used to assess OCTT in the research frame only due to its laxative action; inulin breath test, devoid of this bias, could be replacing it. However, the main limitation in the use of breath tests in the OCTT determination is their low reproducibility.

Breath tests sustainability in hospital settings: cost analysis and reimbursement in the Italian National Health System.

The high demand of Breath Tests (BT) in many gastroenterological conditions in time of limited resources for health care systems, generates increased interest in cost analysis from the point of view of the delivery of services to better understand how use the money to generate value. This study aims to measure the cost of C13 Urea and other most utilized breath tests in order to describe key aspects of costs and reimbursements looking at the economic sustainability for the hospital. A hospital based cost-analysis of the main breath tests commonly delivery in an ambulatory setting is performed. Mean salary for professional nurses and gastroenterologists, drugs/preparation used and disposable materials, purchase and depreciation of the instrument and the testing time was used to estimate the cost, while reimbursements are based on the 2013 Italian National Health System ambulatory pricelist. Variables that could influence the model are considered in the sensitivity analyses. The mean cost for C13--Urea, Lactulose and Lactose BT are, respectively, Euros 30,59; 45,20 and 30,29. National reimbursement often doesn't cover the cost of the analysis, especially considering the scenario with lower number of exam. On the contrary, in high performance scenario all the reimbursement could cover the cost, except for the C13 Urea BT that is high influenced by the drugs cost. However, consideration about the difference between Italian Regional Health System ambulatory pricelist are done. Our analysis shows that while national reimbursement rates cover the costs of H2 breath testing, they do not cover sufficiently C13 BT, particularly urea breath test. The real economic strength of these non invasive tests should be considered in the overall organization of inpatient and outpatient clinic, accounting for complete diagnostic pathway for each gastrointestinal disease.

Assessment of nutritional status of gastroenterology patients in Croatia.

Malnutrition is a common feature of gastroenterological diseases. In this study, nutritional status of the patients admitted to Department of Gastroenterology at University Hospital Center Zagreb was assessed. Anthropometric, dietetic, biochemical methods and method of Subjective Global Assessment (SGA) was used. The study group included 284 patients admitted to the Hospital. Malnutrition, as defined by SGA, was found in 61.1% of the patients, of whom 75% were moderately and 25% severely malnourished. Those patients classified as moderately and extremely malnourished by SGA were found to have statistically lower values of BMI, albumin, total proteins, calcium, iron, triglycerides, cholesterol, vitamin A and lymphocytes as compared to those who were adequately nourished. The prevalence of malnutrition in hospitalized patients treated at the Department of Gastroenterology is high. The use of nutritional screening with multiple measures would be important in the early identification and treatment of these patients and would help decrease this high prevalence.

Assessment of hypolactasia and site-specific intestinal permeability by differential sugar absorption of raffinose, lactose, sucrose and mannitol.

The sugar absorption test is a non-invasive test for investigating intestinal permeability by simultaneous measurement of four probe sugars. In this study, we evaluated the utility of raffinose, lactose, sucrose and mannitol as probe sugars and calculated their urinary recovery as a percentage of ingested dose (mol/mol) and the recovery ratios of raffinose/mannitol, lactose/ raffinose and sucrose/raffinose. The reference ranges for these ratios, established from 39 healthy volunteers, are 0.005-0.015, 0.13-0.63 and 0.09-0.47, respectively. This sugar absorption test was performed in three patient groups. i) In 109 patients with aspecific gastrointestinal symptoms of whom intestinal histology was studied by duodenal biopsies: the urinary raffinose/mannitol recovery ratio highly correlated with gradation of duodenal damage; the sensitivity and specificity of the raffinose/mannitol ratio for detection of intestinal damage were 93% and 91%, respectively, using a cut-off level of 0.020. ii) In 70 patients in whom intestinal lactase activity was investigated by the lactose tolerance test: the urinary lactose/raffinose recovery ratio provided high diagnostic accuracy for hypolactasia (sensitivity 81% and specificity 89% at a cut-off level of 0.70). In analogy with the lactose/raffinose ratio, we suppose that the sucrose/raffinose ratio can be used as a marker of hyposucrasia. iii) In 40 patients with localized small intestinal damage, Crohn's disease of the ileum (n = 21) and celiac disease with histologically proven duodenal damage (n = 19): the raffinose/mannitol recovery ratio was increased in 100% of patients with celiac disease and in 81% of patients with Crohn's disease; increased lactose/raffinose recovery ratio (hypolactasia) and increased sucrose/raffinose (hyposucrasia) were present in 89% and 95% of celiac patients and 19% and 0% of Crohn's disease patients, respectively. The combination of the raffinose/mannitol ratio and sucrose/raffinose ratio appears to be an indication of the distribution of intestinal damage.

Use of the 13C-octanoic acid breath test for assessment of solid-phase gastric emptying in dogs.

OBJECTIVE: To assess the 13C-octanoic acid breath test for determining gastric emptying in dogs. ANIMALS: 6 healthy adult dogs. PROCEDURE: Food was withheld for 12 hours before each test. Expired air was collected 30 minutes and immediately before each test and at frequent intervals thereafter for 6 hours. Concentration of 13CO2 in expired air was determined by use of continuous-flow isotope-ratio mass spectrometry. Basal concentration of 13CO2 was measured in dogs that were not fed a test meal. Effects of the standard unlabeled test meal on basal concentration of 13CO2 were then assessed. The optimum dose of substrate was determined by measuring 13CO2 concentration after ingestion of the standard test meal containing 50 or 100 mg of 13C-octanoic acid, whereas effect of energy density of the test meal on gastric emptying was determined after ingestion of the standard or high-energy labeled test meal. Gastric emptying coefficient (GEC), time to peak 13CO2 concentration (tmax), and half-dose recovery time (t(1/2)) were calculated. RESULTS: Basal concentration of 13CO2 in expired air was not significantly affected by ingestion of the unlabeled test meal. However, 13CO2 concentration significantly increased in a dose-dependent manner after ingestion of the labeled meal. Gastric emptying coefficient, and were significantly different between dogs fed the standard and high-energy test meals, indicating that ingestion of a high-energy meal delays gastric emptying. CONCLUSIONS AND CLINICAL RELEVANCE: The 13C-octanoic acid breath test may be a useful noninvasive and nonradioactive method for assessment of gastric emptying in dogs.

Nutritional assessment.

Nutritional status is a dynamic entity that changes because of interactions between nutrient intake and absorption and requirements and disease. Clinically relevant nutritional assessment should determine whether the patient's nutritional status will decline in the absence of nutritional support. In addition, such assessment should predict complications in the absence of nutritional intervention. The role of different techniques--clinical body compositional, and functional--is discussed in this context.

NSAIDs, gastrointestinal injury, and cytoprotection.

Gastrointestinal toxicity caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is the most frequent drug side effect in the United States. NSAIDs are implicated in the development of complicated peptic ulcer disease and injury to the small bowel and colon. NSAIDs interfere with prostaglandin-mediated epithelial defense mechanisms and also cause direct epithelial toxicity. Current and future approaches to the prevention and management of NSAID injury are reviewed.

Resting energy expenditure in patients with newly detected gastric and colorectal cancers.

Resting energy expenditure (REE) was measured in 104 patients with newly detected gastric or colorectal (GCR) cancer and was compared with two groups of control subjects without cancer: healthy subjects (H control subjects) and patients with nonmalignant diseases of the gastrointestinal tract (GI patients). REE in GCR-cancer patients was not significantly different from REE in GI patients or H control subjects. Comparison of measured REE with predicted REE obtained from prediction equations may erroneously suggest that increased REE is a contributing factor in the development of cancer cachexia. No significant differences in REE were found when patients with liver metastases were compared with patients without metastases. There were no differences in REE between gastric and colorectal cancer patients. The decrease in energy expenditure, which normally occurs during starvation and weight loss in healthy men and women, could not be demonstrated in weight-losing, GCR-cancer patients. In conclusion, elevation of REE contributes little to the pathogenesis of cancer cachexia in GCR-cancer patients.

Protein status and metabolic expenditure determine the response to intravenous nutrition--a new classification of surgical malnutrition.

To determine whether nutritional and metabolic factors affect the response to intravenous nutrition (IVN) 146 surgical patients were classified according to their protein and metabolic status using direct measurements of body protein and metabolic expenditure. The patients were grouped into four categories: category I, moderate to severe protein depletion without raised metabolic expenditure; category II, moderate to severe protein depletion with raised metabolic expenditure; category III, mild protein depletion without raised metabolic expenditure; and category IV, mild protein depletion with raised metabolic expenditure. After 2 weeks of IVN patients in category I gained a mean(s.e.m.) of 0.43(0.06) kg of body protein (P less than 0.001) and had significant rises in both plasma transferrin and prealbumin (P less than 0.05); patients in category II gained 0.30(0.11) kg of protein (P less than 0.005) and also had significant rises in transferrin and prealbumin (P less than 0.05). Patients in category III lost 0.24(0.11) kg protein (P less than 0.05) and had no changes in either transferrin or prealbumin and patients in category IV lost 0.51(0.13) kg of body protein (P less than 0.001) and although there was a significant rise in plasma prealbumin there was no significant change in plasma transferrin. When postoperative patients were examined separately, they did not differ significantly from preoperative patients except in category I, where their protein gain was only 0.19(0.10) kg, an amount not significantly different from that gained by patients in category II. In each of the four categories described, the changes in total body protein occurring with 2 weeks of IVN were determined by the relative effects of two competing processes; protein depletion and raised metabolic expenditure. With moderate to severe protein depletion (approximately 30 per cent depletion of body protein stores) there was a marked tendency to gain protein with IVN. When the patient had a raised metabolic expenditure or was postoperative this tendency of depleted patients to gain protein was still present but it was less. With only mild protein depletion (approximately 10 per cent depletion) increases in metabolic expenditure made it difficult, if not impossible, to prevent continuing protein loss in spite of aggressive nutritional support. The patient categories we have described determine the response to IVN and form the basis of a new clinical classification of surgical malnutrition.

Resting energy expenditure in lung and colon cancer.

Elevated resting energy expenditure (REE) is a possible mechanism of cancer cachexia. We measured REE by whole-body direct calorimetry in patients with colon and non-small cell lung cancer and compared the results with REE in groups of healthy subjects and in patients with anorexia nervosa, with nonmalignant gastrointestinal (GI) disease, with miscellaneous reasons for weight loss, and with chronic lung disease. The mean REE of the cancer patients was not different from healthy subjects, those with GI disease, miscellaneous causes of cachexia, and chronic lung disease, and there was no significant difference in REE between those cancer patients with weight loss and controls with weight loss, except for the anorexia nervosa patients. The REE of the anorexia nervosa patients (female) was significantly lower than the REE of females with lung cancer. Weight loss correlated with REE in female lung cancer patients. Serial comparison of REE of ten cancer patients who lost 5% to 18% of their body weight during study showed no consistent change in REE. We conclude that patients with colon and non-small cell lung cancer, including those with weight loss, have REE similar to normal controls. Relative hypermetabolism may contribute to cancer cachexia, as may absolute hypermetabolism in some subsets of cancer patients.

Nutritional assessment in patients with chronic gastrointestinal symptoms: comparison of functional and organic disorders.

We assessed the nutritional status of 119 patients with chronic gastrointestinal symptoms due to organic disorders (inflammatory bowel disease, IBD; peptic ulcer, PU; malabsorption syndrome, M; and malignant gastrointestinal tumours, T), by standard anthropometry and marker proteins (albumin; retinol-binding protein, RBP; and thyroxine-binding prealbumin, TBPA). We also studied 31 patients with irritable bowel syndrome (IBS) and 75 age-matched healthy controls (C). Compared with healthy controls, patients with organic bowel disease had significant abnormality of two or more anthropometric measurements (P less than 0.05). Plasma albumin was reduced in patients with IBD, M and T (P less than 0.001), but RBP and TBPA measurements were lower in all patient categories (P less than 0.01) including IBS. Stepwise discriminant analysis of the patient data alone, using three to six parameters, correctly separated 65 per cent PU patients, 66 per cent IBD and M, 72 per cent IBS and 88 per cent patients with T from other disease categories. We conclude that patients with chronic gastrointestinal symptoms often have some nutritional disturbances and that simple anthropometric and protein measurements might help us to distinguish patients with functional bowel disease from those with organic bowel disease.

Metabolic and respiratory effects of continuous and discontinuous lipid infusions. Occurrence in excess of resting energy expenditure.

Intravenous hyperalimentation with dextrose can be associated with adverse respiratory and hepatic effects. The purpose of this study was to determine the respiratory and metabolic consequences of fat calories in excess of resting energy expenditure provided both continuously and discontinuously. No significant changes in respiratory mechanics, oxygen consumption, carbon dioxide production, resting energy expenditure, serum substrates, liver function, or nitrogen balance were noted by the addition of 500 kcal of lipid emulsion to dextrose calories sufficient to meet energy requirements. The respiratory quotient declined significantly with the 12- and 24-hour lipid infusions, but persisted for the entire 24 hours only in the latter instance. The sustained and increased (46% v 36%) oxidation of lipid with a 24-hour infusion suggests that a continuous infusion of lipid is preferable to a discontinuous infusion.