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Biomedical subjects

D F Driscoll

Publications and source records attributed to D F Driscoll.

At least 19 recordsLinked to original sources

Physicochemical stability of intravenous lipid emulsions as all-in-one admixtures intended for the very young.

BACKGROUND & AIMS: Intravenous lipid emulsions (IVLEs) are unstable when growth of lipid droplets into large fat globules is detected by appropriate particle sizing techniques. Specifically, instability is evident when the volume-weighted percent fat (PFAT)>5 microm exceeds 0.4% of the total lipids present. This represents an approximate 10-fold increase in the population normally present in the large-diameter tail of stable lipid emulsions. The composition of the oil phase of an IVLE, however, has been shown to exhibit different stability characteristics. We investigated the stability of various IVLEs containing physical mixtures of medium-(MCT) and/or long-chain triglycerides (LCT) in three different all-in-one (AIO) admixtures intended for neonatal and infant patients. METHODS: The 20% (w/v) IVLEs used in this study were composed of the following oils (by weight): 1). 1:1-soybean/safflower (SS); 2). 1:1-MCT:soybean (MS); and 3). 5:4:1-MCT:soybean:fish (MSF). Stability was assessed by light obscuration or light extinction to count large fat globules, and by aided (microscopic) and unaided (naked eye) visual assessments for up to 48 h at room temperature. RESULTS: The stability of SS-based admixtures significantly and rapidly deteriorated in one of the three AIO compositions studied, whereas the AIOs made from MS or MSF were stable for all formulations. CONCLUSION: The results suggest that AIOs made from MCT/LCT-containing IVLEs are more stable than those made from pure LCTs.

Analysis of Variance↗

Physicochemical assessments of parenteral lipid emulsions: light obscuration versus laser diffraction.

The United States Pharmacopeia (USP) has proposed a new Chapter <729> entitled 'Globule Size Distribution in Intravenous Emulsions' that is intended to identify methods for analyzing the stability of lipid emulsions. We studied the differences between particle-sizing instruments when analyzing the physicochemical stability of a parenteral nutrition mixture compounded with intravenous lipid emulsion, known as an all-in-one mixture. As the growth of lipid droplets, i.e. coalescence, signals an irreversible change in emulsion stability, we focused our investigation on the large diameter tail (>5 microm) of the globule size distribution. Of the four proposed methods, droplet size was studied over a range of mixture stabilities using a low osmolality parenteral nutrition formula employing both light scattering and light obscuration techniques. In addition, the same mixtures were also freshly prepared, and then spiked with a known amount of 5 microm latex spheres. The response obtained from the light obscuration technique was linear and detected both unstable and latex-spiked mixtures in every case for droplets or particles >5 microm. The results of the laser diffraction method were non-linear and overestimated, was less sensitive or missed entirely, globules or particles in the large diameter tail of the dispersion. The results demonstrate that light obscuration is superior to laser diffraction in identifying unstable intravenous fat emulsions.

Chemical Phenomena↗

Physicochemical stability assessments of lipid emulsions of varying oil composition.

BACKGROUND AND AIMS: Intravenous lipid emulsions have been shown to be unstable when the percent fat >5 microm (PFAT >5 microm) exceeds 0.4% by weight of the total fat present. We investigated the physicochemical stability of a standard low amino acid and carbohydrate mixture containing electrolytes when combined with four different commercial intravenous lipid emulsions of varying oil composition. METHODS: The 20% (w/v) lipid emulsions studied were composed of the following oils (by weight): 1) 1 : 1 soybean/safflower (SS); 2) 100% soybean (S); 3) 1 : 1 soybean/MCT (SM) and 4) 4 : 1 olive/soybean (OS). Physicochemical stability was assessed by light obscuration or extinction using a single-particle optical sensing technique to detect growth of fat globules in the large diameter tail (>1 microm) of the droplet size distribution and by visual analyses for evidence of phase separation. RESULTS: The physicochemical stability of SS and S-based all-in-one mixtures significantly deteriorated over time when compared to the mixtures made from SM and OS. In addition, of the four mixtures studied that contained SS (n=2) and S (n=2), only one of each bag studied showed visually obvious destabilization by the presence of free oil from phase separation, despite highly abnormal changes in the globule size distribution of all four preparations. CONCLUSION: The results suggest that all-in-one mixtures composed of either soybean oil alone or in combination with safflower oil are less stable than those mixed with either MCT or olive oil which also contain sodium oleate that can act as co-emulsifying agent.

Chemical Phenomena↗

Essential fatty acid deficiency and home total parenteral nutrition patients.

The requirements for essential fatty acids in patients on home parenteral nutrition are not well described. We therefore studied the needs of 12 patients receiving parenteral nutrition for at least 4 mo (range: 4 mo-17.3 yr; mean 7.0 +/- 5.2 yr). Prior to the study, each patient had been receiving intravenous lipids either weekly or biweekly and had a triene to tetraene ratio (TTR) on plasma phospholipids performed at least annually. A TTR > or = 0.2 was considered diagnostic for essential fatty acid deficiency (EFAD). The purpose of this study was to determine the required intravenous lipid supplementation in patients on home total parenteral nutrition (HTPN). Patients with an initial TTR of < 0.2 had their intravenous lipid stopped and changes in their serum phospholipid fatty acids were followed every 3-4 wk. Nine of 12 patients had TTRs > 0.2 at some point in the study. Phase I consisted of patients who at initiation of the study had normal TTRs and were taken off lipid supplementation until their TTR became abnormal. Phases II, III, IV, and V consisted of lipid delivered in total nutrient admixtures in biweekly doses of 0.6, 1.2, 1.8, and 2.4 g of fat/kg bodyweight, respectively. Eight patients normalized their TTRs on the biweekly lipid regimens; one patient expired before his ratio normalized; and three patients could not be made deficient in essential fatty acids after 26 or more wk of fat-free parenteral nutrition. Most patients required 1.2 to 2.4 g of lipid/kg bodyweight/biweekly to correct serologic EFAD. The clinical background, as well as the length of small bowel remaining, did not seem to identify those patients who required lipid supplementation nor the final dose of lipid needed to normalize their TTRs.

Adult↗

Early enteral feeding in postsurgical cancer patients. Fish oil structured lipid-based polymeric formula versus a standard polymeric formula.

OBJECTIVES: The authors compared the safety, gastrointestinal tolerance, and clinical efficacy of feeding an enteral diet containing a fish oil/medium-chain triglyceride structured lipid (FOSL-HN) versus an isonitrogenous, isocaloric formula (O-HN) in patients undergoing major abdominal surgery for upper gastrointestinal malignancies. SUMMARY BACKGROUND DATA: Previous studies suggest that feeding with n-3 fatty acids from fish oil can alter eicosanoid and cytokine production, yielding an improved immunocompetence and a reduced inflammatory response to injury. The use of n-3 fatty acids as a structured lipid can improve long-chain fatty acid absorption. METHODS: This prospective, blinded, randomized trial was conducted in 50 adult patients who were jejunally fed either FOSL-HN or O-HN for 7 days. Serum chemistries, hematology, urinalysis, gastrointestinal complications, liver and renal function, plasma and erythrocyte fatty acid analysis, urinary prostaglandins, and outcome parameters were measured at baseline and on day 7. Comparisons were made in 18 and 17 evaluable patients based a priori on the ability to reach a tube feeding rate of 40 mL/hour. RESULTS: Patients receiving FOSL-HN experienced no untoward side effects, significant incorporation of eicosapentaenoic acid into plasma and erythrocyte phospholipids, and a 50% decline in the total number of gastrointestinal complications and infections compared with patients given O-HN. The data strongly suggest improved liver and renal function during the postoperative period in the FOSL-HN group. CONCLUSION: Early enteral feeding with FOSL-HN was safe and well tolerated. Results suggest that the use of such a formula during the postoperative period may reduce the number of infections and gastrointestinal complications per patient, as well as improve renal and liver function through modulation of urinary prostaglandin levels. Additional clinical trials to fully quantify clinical benefits and optimize nutritional support with FOSL-HN should be undertaken.

Adolescent↗

Physicochemical stability of total nutrient admixtures.

The effect of six independent factors on the stability of i.v. nutritional emulsions was studied. Forty-five i.v. nutritional admixtures were prepared, each containing the following: (1) amino acids (range, 2.5-7%), (2) hydrated glucose (range, 5-20%), (3) lipid emulsion (range, 2-5%), (4) monovalent cations (range, 0-150 meq/L), (5) divalent cations (range, 4-20 meq/L), and (6) trivalent cations (range, 0-10 mg of elemental iron/L). Stability assessments included particle-size analysis, pH determination, and visual inspection. Sizing and counting of fat particles was achieved by using light obscuration and dynamic light scatter methods. Light obscuration and visual assessments were performed at 0, 6, 12, 24, and 30 hours. Dynamic light scatter and pH determinations were performed at 0 and 30 hours. Multiple stepwise regression analysis revealed that trivalent cation concentration was the only variable that affected the stability of nutritional emulsions (p < 0.00001), accounting for approximately 60% of the potentially dangerous increases in fat particle sizes observed. In addition, a percentage of large fat particles (> 5 microns in diameter) greater than 0.4% was associated with unstable emulsions. However, this instability was visibly evident only 65% of the time. Changes in mean globule diameter, cream-layer thickness, and pH did not reveal instability in these emulsions. Emulsions in which > 0.4% of the initial fat concentration consists of particles of > 5 microns in diameter are likely to become unstable. Of the six factors studied, the trivalent cation in iron dextran was most disruptive to lipid-based parenteral nutrient admixtures.

Amino Acids↗

Total nutrient admixtures: theory and practice.

The use of total nutrient admixtures (TNA) has increased dramatically in both the clinical and home care setting since 1983. The popularity of these dosage forms rests in supplying all the nutrients in one container that meets the nutritional goals of the patient. In addition, TNA formulations obviate the need for either separate peripheral venous catheters or co-infusions into the primary venous line, thus simplifying this complex therapy. Moreover, the clinical benefits derived from this practice are related to a reduction in glucose-associated complications that assume particular importance in the acutely ill patient. Although much experience has been gained over the last 12 years, practice standards vary with the institution. Despite this, TNA therapy has been successful in the U.S. This paper attempts to delineate the important physicochemical variables that influence emulsion stability as they relate to clinical practice.

Chemistry, Pharmaceutical↗

Tumor and host response to arginine and branched chain amino acid-enriched total parenteral nutrition. A study involving Walker 256 carcinosarcoma-bearing rats.

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.

Amino Acids, Branched-Chain↗