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PubMed2002

The distribution of long range admixture linkage disequilibrium in an African-American population.

OBJECTIVES: To better understand the effect of admixture on long range linkage disequilibrium (LD), we characterized extended LD in gene-rich regions of an African-American population. METHODS: Approximately 290 cM of chromosomes 1, 3, 6, 11-17, 20 and 22 were scanned using 109 polymorphic microsatellite markers spaced an average of 3 cM apart. Disequilibrium between loci (D') was based on maximum-likelihood estimates of haplotype frequencies computed for 200 unrelated African Americans. RESULTS: Mean D' values were highest on chromosomes 6p23-p21.3 (D' = 0.33) and 15p22.2-p25.3 (D' = 0.34), and lowest on chromosome 12p11.2-q14 (D' = 0.21). Overall, the variance in LD among chromosomes accounted for approximately two-thirds of the total LD variance. Of the 434 locus pairs spaced between 0.3 and 38.7 cM apart, there was no detectable correlation between LD and recombination distance and a weak negative correlation between LD and physical distance (r(s) = -0.12; p = 0.031). For the 192 intrachromosomal locus pairs where allele frequency data were available from the Centre d'Etude du Polymorphisme humain (CEPH), we found a statistically significant positive correlation between LD and the allelic frequency differences (delta) between the African-American study population and Caucasian reference CEPH population (r(s) = 0.53; p < 0.0001). The correlation between LD and both recombination and physical distance was markedly increased for locus pairs with high delta levels. CONCLUSIONS: Our results suggest that recent Caucasian admixture maintains a high level of long range LD in African Americans on a genomic scale, and selected markers with large African American/Caucasian delta levels may be useful in association studies.

Alleles↗
PubMed1984

Admixture analysis of plasma cholesterol levels in a Jewish population sample in Jerusalem.

The frequency distribution of total plasma cholesterol levels (TC) in 17-year-old Jerusalem youngsters and their parents (n = 6,170) was examined for evidence of admixture of normal distributions. Probability plots indicated bimodality of age-adjusted TC in both sexes. Using a maximum likelihood procedure, two normal distributions fitted the age- and sex-adjusted data significantly better than 1, with 0.9% males and 1.2% females coming from a lower distribution 2-3 standard deviations below the major mode and 0.2% males and 1.1% females belonging to the higher distribution. These results suggest that single genes may determine high as well as low cholesterol levels, but are open to other interpretations, and thus require confirmation by segregation analysis. Jews originating from Europe showed the highest TC levels followed by those from Israel, Asia, and Africa. Adjustment of TC for ethnicity did not alter the above estimates. Analysis of bimodality within countries of origin showed greater separation of the distributions in Asian and Israeli origin groups than in European and North African groups, in whom there was less evidence for admixture.

Adolescent↗
PubMed1990

Clinical experience with three-in-one admixtures administered peripherally.

The purpose of this report was to describe the tolerance of hyperosmolar nutritionally complete solutions infused peripherally, as a bridge to enteral therapy in the surgical patient. Solutions providing approximately 40% of calories as carbohydrates were administered to 23 surgical patients with the fats, amino acids, and dextrose mixed in one container. Final osmolarity, when measured directly with additives, ranged from 1200-1350 mOsm/L. Approximately 85% of the patients had acceptable tolerance to this new technique. The patient tolerance of the high osmolar admixture in peripheral veins might be attributed to the buffering and dilution effect of the IV fats in combination with the higher pH of the amino acid solutions and the addition of heparin to the admixture. Strong support for this technique was voiced by experienced nutritional support physicians and hospital personnel for use in surgical patients who have immediate short-term needs.

Adult↗
PubMedDate not supplied

Physicochemical stability of two types of intravenous lipid emulsion as total nutrient admixtures.

BACKGROUND: Recent data have demonstrated that total nutrient admixtures (TNAs) are unstable when the percentage of fat (PFAT) globules >5 microm in diameter constitute >0.4% of the total fat present and therefore can be considered pharmaceutically unfit for human administration. METHODS: We studied five nutritionally balanced TNAs using two different products of different oil composition designed to feed adult patients weighing 40 to 80 kg in 10 kg increments, which were given in final volumes equal to 25 mL/kg. Final concentrations of amino acids, dextrose, and lipids were held constant for each weight level. To provide cationic stress within clinical limits, calcium and magnesium were given in amounts equal to three times the usual daily dose, at 15 mmol each. Five TNAs were made in duplicate and for each product (n = 20) and studied over 5 days. Lipid droplet counts were determined by laser light extinction and conducted at five intervals; immediately after preparation at time 1 (T1), after 4 days at 4 degrees C +/- 2 degrees C (T2), and then at 6 (T3), 24 (T4), and 30 (T5) hours during storage at 25 degrees C +/- 1 degree C. At T3, a simulated patient infusion, set at a rate to deliver the entire volume over the next 24 hours, was begun. Samples taken at T3, T4, and T5, equal to 0, 18, and 24 hours, respectively, of the simulated patient infusion, were collected from the terminal infusion port of the i.v. administration set. Mean particle size (MPS) was determined by dynamic light scatter at T1, T3, and T5. Dependent variable analyses included the PFAT globules > 1.75 and 5 microm and MPS. A repeated-measure two-way ANOVA assessing treatment and time was performed. RESULTS: The MCT/LCT-based TNAs had significantly fewer enlarged fat globules >1.75 microm (p < .0001) and >5 microm (p = .046), and smaller MPS (p < .0001) than TNAs made with the pure LCT emulsion. Of the 20 TNAs studied, 4 demonstrated visible evidence of instability (ie, heavy creaming or free oil), each occurring on day 5 only with the 70- and 80-kg LCT-based TNAs, and no evidence of instability with admixtures prepared from MCT/LCT lipid emulsions (chi2 analysis: p < .05). CONCLUSIONS: Because the final macronutrient concentrations were held constant, the instability seen with the LCT-based TNAs of higher volumes may result from dilution of the electrolyte concentrations that unfavorably alters the electrical double layer and irreversibly commits the emulsion to an unstable state. The greater physicochemical stability achieved with the MCT/LCT-based TNAs, in turn, likely results from the smaller lipid droplet sizes, which may be an inherent property of MCTs.

Chemical Phenomena↗
PubMedDate not supplied

The stability of amikacin, gentamicin, and tobramycin in total nutrient admixtures.

Amikacin (A), gentamicin (G), and tobramycin (T) were added to eight different total nutrient admixtures (TNA) with varying concentrations of dextrose, amino acid, and fat emulsion to determine drug and emulsion stability. All TNA were prepared aseptically and stored at room temperature under normal room lighting for 12 hr before drug addition. One volume of each drug was added to an equal volume of each of the eight TNAs to simulate 1:1 piggyback contact volumes. Samples were left at room temperature for 6 hr. Drug concentrations were analyzed by fluorescence polarization immunoassay. TNA/drug admixtures were pH tested and visually inspected before and after centrifugation in microhematocrit tubes, noting signs of emulsion stability at 1 and 6 hr. Emulsion particle size was determined at 1 and 6 hr using interference contrast microscopy. All three drugs retained their immunoreactivity in all TNAs for at least 6 hr. G and T were stable in all eight TNAs for at least 6 hr with no significant effect on emulsion particle size or stability after centrifugation. A was incompatible with all eight TNAs, resulting in visual breaking of all emulsions within 1 hr. Therefore, G and T, but not A, can be administered via piggyback method with the eight TNAs tested if the infusion is completed within 6 hr.

Amikacin↗
PubMedDate not supplied

Staphylococcus saprophyticus sepsis related to total parenteral nutrition admixtures contamination.

The aim of this study was to report an outbreak of sepsis related to contamination of total parenteral nutrition (TPN) admixtures with Staphylococcus saprophyticus. A total of four patients developed fever after administration of contaminated TPN. Results of cultures of blood, catheter hubs and tips, and TPN admixtures are presented. The strain responsible for the outbreak was able to grow in vitro in two common TPN formulations.

Aged↗
PubMedDate not supplied

Total nutrient admixtures appear safer than lipid emulsion alone as regards microbial contamination: growth properties of microbial pathogens at room temperature.

BACKGROUND: The extraordinary growth properties of most microorganisms in 10% and 20% lipid emulsions has led to the Centers for Disease Control and Prevention recommendation that if lipids are given through an i.v. line, the administration set should be replaced every 24 hours rather than the usual 72-hour interval used for crystalloid solutions, including those used for conventional total parenteral nutrition. For nearly 15 years, parenteral alimentation has been given as a total nutrient admixture (TNA), with the glucose, amino acids, and lipid mixed within the same bag and infused continuously over 24 hours. METHODS: We prospectively studied in a representative TNA (17.6% glucose, 5% amino acids, 4% lipid; pH 5.6, osmolality 1778) and in a control solution, 5% dextrose-in-water (D5%/W), the growth properties at 4, 25, and 35 degrees C of three isolates each of Staphylococcus epidermidis, Staphylococcus aureus, Enterobacter cloacae, Klebsiella oxytoca, Serratia marcescens, Acinetobacter calcoaceticus, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, Burkholderia cepacia, Flavobacterium spp, and Candida albicans, and two isolates of Staphylococcus saprophyticus, the species that are most likely to contaminate TNA during preparation or administration and that have been implicated in >95% of all outbreaks and sporadic cases of nosocomial bloodstream infections traced to contaminated parenteral admixtures reported in the world literature. RESULTS: Growth in TNA at 25 and 35 degrees C occurred with only two species, C. albicans and S. saprophyticus, and only after 24 to 48 hours; D5%/W allowed growth at 25 degrees C of two gram-negative species, S. marcescens and B. cepacia. CONCLUSIONS: We conclude that TNA is a poor growth medium for most nosocomial pathogens and is no better than D5%/W. The need to replace administration sets every 24 hours with TNA should be reconsidered and ideally be studied in a prospective randomized trial.

Acinetobacter↗
PubMed1999

Propofol-thiopentone admixture-hypnotic dose, pain on injection and effect on blood pressure.

This study examined some pharmacodynamic characteristics of two admixtures of propofol and thiopentone. Ninety unpremedicated ASA 1 or 2 patients were group-randomized to receive, in a double-blinded manner, one of the following mixtures for induction of anaesthesia: Group P50: propofol 1% 10 ml/thiopentone 2.5% 10 ml; Group P75: propofol 1% 15 ml/thiopentone 2.5% 5 ml; Group P100: propofol 1% 20 ml/lignocaine 1% 4 ml. An additional 30 randomized but unblinded patients from the same patient cohort received thiopentone 2.5% to provide predictive dose data for groups P50 and P75. Haemodynamic data were collected pre- and post-induction. The required induction dose of both mixtures of propofol and thiopentone found an additive rather than a synergistic interaction with no significant difference between predicted and observed dose. Thiopentone resulted in significantly more rapid induction of anaesthesia than propofol/lignocaine or propofol/thiopentone. The addition of thiopentone to propofol was found to be as efficacious as the mixing of lignocaine with propofol in reducing pain on injection. The fall in systolic blood pressure was significantly less in group P50 compared with groups P75 or P100. Admixture of thiopentone with propofol results in an additive hypnotic effect, a reduction in pain of injection (comparable with addition of lignocaine) and a reduced hypotensive response compared to propofol injection alone during induction.

Adolescent↗
PubMed1981

Prediction of the stability of meclofenoxate injection in parenteral admixtures.

A new method for predicting pharmaceutical stability in parenteral admixtures was studied using meclofenoxate hydrochloride injection as a model preparation. The pH and temperature of clinical parenteral admixtures are not constant, unlike experimental buffer solutions, and it is impossible to predict the accurate degradation ratio by the preceding method described by many authors. This study provides a solution to this problem making possible the accurate prediction of degradation ratios of pharmaceuticals even in such complicated systems.

Drug Stability↗
PubMed2000

Risk for rheumatic disease in relation to ethnicity and admixture.

Risk of systemic lupus erythematosus (SLE) is high in west Africans compared with Europeans, and risk of rheumatoid arthritis (RA) is high in Native Americans compared with Europeans. These differences are not accounted for by differences in allele or haplotype frequencies in the human leucocyte antigen (HLA) region or any other loci known to influence risk of rheumatic disease. Where there has been admixture between two or more ethnic groups that differ in risk of disease, studies of the relationship of disease risk to proportionate admixture can help to distinguish between genetic and environmental explanations for ethnic differences in disease risk and to map the genes underlying these differences.

Africa↗
PubMed2005

Early ethnic difference in insulin-like growth factor-1 is associated with African genetic admixture.

IGF-1 is a growth-promoting hormone. Numerous studies have reported higher systemic concentrations of IGF-1 among African Americans (AA) compared with European Americans (EA) before puberty. We conducted this cross-sectional analysis to determine whether African ancestral genetic background, dietary factors, energy expenditure, adiposity, and socioeconomic status contribute to this difference. Children were prepubertal, AA and EA males and females. Genetic admixture was assessed from approximately 20 ancestry informative genetic markers. Body composition was determined by dual-energy x-ray absorptiometry; intake of energy, carbohydrate, protein, and fat by 24-h dietary recall; activity-related energy expenditure by doubly labeled water and indirect calorimetry; and socioeconomic status (SES) according to the Hollingshead scale. IGF-1 and IGF binding protein-3 (IGFBP-3) were measured using immunoradiometric assays. AA children had significantly greater IGF-1 compared with EA children (p < 0.01). In addition, AA children had lower SES and greater protein intake relative to EAs (p < 0.05 for both). Multiple linear regression analysis revealed that the only significant independent predictors of IGF-1 were IGFBP-3 and African admixture (p < 0.01 for both). Thus, our data suggest that the greater IGF-1 of AA relative to EA children could have a genetic basis.

Adiposity↗
PubMed2004

Characterization of admixture in an urban sample from Buenos Aires, Argentina, using uniparentally and biparentally inherited genetic markers.

In this study we analyzed a sample of the urban population of La Plata, Argentina, using 17 mtDNA haplogroups, the DYS 199 Y-chromosome polymorphism, and 5 autosomal population-associated alleles (PAAs). The contribution of native American maternal lineages to the population of La Plata was estimated as 45.6%, whereas the paternal contribution was much lower (10.6%), clearly indicating directional mating. Regarding autosomal evidence of admixture, the relative European, native American, and West African genetic contributions to the gene pool of La Plata were estimated to be 67.55% (+/-2.7), 25.9% (+/-4.3), and 6.5% (+/-6.4), respectively. When admixture was calculated at the individual level, we found a low correlation between the ancestral contribution estimated with uniparental lineages and autosomal markers. Most of the individuals from La Plata with a native American mtDNA haplogroup or the DYS199*T native American allele show a genetic contribution at the autosomal level that can be traced primarily to Europe. The results of this study emphasize the need to use both uniparentally and biparentally inherited genetic markers to understand the history of admixed populations.

Argentina↗
PubMed1980

Response of pulmonary venous admixture. A means of comparing therapies?

Patients who require cardiopulmonary bypass have a reproducible increase in interstitial pulmonary water and pulmonary venous admixture, a decrease in functional residual capacity, and a mild arterial hypoxemia. Therefore, such patients are good subjects for evaluating therapy with positive end-expiratory pressure and steroids, both of which are controversial. We sought to determine if the response of the pulmonary venous admixture to varying concentrations of inspired oxygen could affect the apparent efficacy of these types of therapy. Results of our study are presented.

Carbon Dioxide↗
PubMed2003

The effect of an admixture of sodium hydrogen phosphate or heparin-coating to poly(D,L)lactide--results of an animal study.

The study was aimed at investigating the effect of an admixture of sodium hydrogen phosphate (NaP) on the pH value around degrading poly(D,L)lactide (PDLLA) and the possible improvement of PDLLA biocompatibility by coating its surface with heparin. PDLLA +/- NaP was injection-molded to form rods (20 x 3 x 2 (mm)) and cubes (3 x 2 x 2 (mm)). Half of the pure PDLLA samples were surface-coated using heparin. One rod and cube each of PDLLA, PDLLA + NaP and PDLLA/Hep were implanted into the dorsal muscles of 42 rats. From the 2nd to 52nd week after operation, pH measurements were performed in the environment around the implants. The samples were then harvested for histological and mechanical analyses. No significant decrease in pH-values was observed in the tissue around the implants. Pure PDLLA and PDLLA/Hep samples were macroscopically resorbed after 52 weeks, while the degradation of PDLLA + NaP was still in progress. Approximately 80% of the initial bending strength of PDLLA or PDLLA/Hep rods was present after six weeks, while the bending strength of PDLLA + Nap was reduced to 50% after 4 weeks. Heparin-coating of PDLLA did not improve its biocompatibility but did increase its resorption. While no significant effect of NaP on pH value was found, its admixture did reduce the mechanical characteristics of the implants.

Animals↗
PubMed2006

Physicochemical stability of highly concentrated total nutrient admixtures for fluid-restricted patients.

PURPOSE: The physicochemical stability of highly concentrated total nutrient admixtures (TNAs) for fluid-restricted patients was studied. METHODS: Five TNAs made from lipid injectable emulsions (50:50 mixture of medium-chain and long-chain triglycerides) designed to meet the full nutritional needs of adults with body weights of 40-80 kg were chosen. Protein was included in the TNAs at 1.5 g/kg for each body weight and was supplied from a concentrated 16% mixture containing the essential and non-essential amino acids. All admixtures were contained in ethylene vinyl acetate bags and were aseptically prepared. Triplicate preparations of each TNA were investigated over 30 hours at room temperature by dynamic light scattering (DLS) and light extinction with single-particle optical sensing (LE-SPOS). RESULTS: No significant changes in the physicochemical stability of the TNAs were observed by DLS (mean droplet size) or LE-SPOS (large-diameter tail) from time 0 (immediately after compounding) to 30 hours. All TNAs met the mean-droplet-size criteria outlined by USP for 20% lipid injectable emulsions. CONCLUSION: Concentrated TNA formulations made from lipid injectable emulsions were stable for 30 hours at room temperature.

Humans↗
PubMed2002

Ready-to-use injection preparations versus conventional reconstituted admixtures: economic evaluation in a real-life setting.

OBJECTIVE: To measure, in a real-life setting, the benefits of using ready-to-use (RTU) injection preparations compared with conventional reconstituted admixtures (Admix) in terms of cost savings. DESIGN AND PERSPECTIVE: An economic model was developed, based on a randomised study. The perspective of the economic evaluation was that of the hospital administration. A microcosting approach was used to determine costs. SETTING: Department of Cardiac Surgery at the Charleroi University Hospital in Belgium. STUDY PARTICIPANTS: Fifty-eight patients undergoing cardiac surgery under cardiopulmonary bypass were randomised to Admix dobutamine or to the RTU dobutamine group and were followed up during 24 hours after initiation of dobutamine therapy. MAIN OUTCOME MEASURES AND RESULTS: Nursing time was reduced by 32% in the RTU group compared with the Admix group. Material cost was also reduced and the overall cost savings in the RTU group amounted to a 60% reduction in the cost of the conventional Admix process (p<0.001). When drug cost was included in the equation, cost savings varied from 1.60 euros (EUR) to EUR21.40 per patient depending on dosage. There was no difference between the two groups in terms of safety and efficacy. A user satisfaction survey showed that medical staff especially welcomed improved ease of preparation and potential for prevention of errors and risks of handling. CONCLUSION: This study confirmed the potential for RTU forms to reduce nursing time associated with preparation and administration of intravenous admixtures and to enable overall cost savings.

Aged↗
PubMed2006

Pharmacogenomics in the Americas: the impact of genetic admixture.

In this review we focus on the impact of genetic admixture on pharmacogenomics in the American continent, where five centuries of intermarriage between Amerindians, European and Africans, resulted in the extensive population heterogeneity observed nowadays. We compare two alternative views of human genomic variation, one stressing populations and the other stressing individuals, and discuss their important and far-reaching consequences to implementation of pharmacogenetics/genomics in practice, especially when dealing with admixed populations. We conclude that a variable mosaic genome paradigm, which envisages the genome of any particular individual as a unique mosaic of variable haplotype blocks--has considerably higher explanation and predictive power for the populations of the Americas. We then move to the more formal pharmacogenomics arena to examine the pharmacogenetic/pharmacogenomic diversity in the Americas and review the challenges and advantages of admixed populations for pharmacogenomic studies. Because interethnic admixture is either common or increasing at a fast pace in many, if not most populations, extrapolation on a global scale of pharmacogenomic data from well-defined ethnic groups is plagued with uncertainty. Intra-ethnic diversity adds complexity to the scientific appraisal, regulatory decisions and, eventually, prescribing of drugs purportedly targeted to a given "race" or ethnicity. Pharmacogenetics/genomics has the potential to benefit people worldwide and to reduce the health disparities between developing and developed nations. This goal is unlikely to be achieved by relinquishing the notion of personalized drug therapy tailored to individual genetic characteristics--the original promise of pharmacogenetics--in favor of a model (pharmacogenomic?) of population-based drug development and prescription, with all its potential pitfalls, especially when extended to admixed populations in developing or developed nations.

Aryl Hydrocarbon Hydroxylases↗
PubMed1979

I.V. admixture profiling: a simple system.

The description of an I.V. admixture profile form is presented. Detailed information on the mechanisms of using this form, as well as the advantages of the profiling system, are delineated. Several examples are illustrated for thorough understanding of the system. The authors conclude that the system affords a simple, accurate, and flexible profiling system which can be utilized in hospital I.V. admixture programs of various sizes. The profiling system provides for a mechanism of clinical involvement as well as for quality assurance assessment.

Drug Compounding↗