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Venous admixture in human septic shock: comparative effects of blood volume expansion, dopamine infusion and isoproterenol infusion on mismatching of ventilation and pulmonary blood flow in peritonitis.

A hemodynamic study with blood gas analysis was performed so we could observe changes induced by blood volume expansion, dopamine infusion and isoproterenol infusion in 20 adult patients suffering from peritonitis complicated with septic shock and acute respiratory failure. Blood volume expansion increased cardiac index (from 2.6 +/- 1.21/min/m2 to 3.4 +/- 1.31/min/m2; p less than 0.001), but also enhanced venous admixture (QS/QT) from 27 +/- 14% to 36 +/- 13%; p less than 0.01). Dopamine infusion increased cardiac index (from 2.6 +/- 0.9 1/min/m2 to 3.4 +/- 1 l/min/m2; p less than 0.001), but also enhanced venous admixture (from 25 +/- 11% to 31 +/- 12%, p less than 0.001). Isoproterenol infusion increased cardiac index (from 2.6 +/- 0.9 l/min/m2 to 3.6 +/- 1.1 l/min/m2; p less than 0.001), but also enhanced venous admixture (from 27 +/- 12% to 33 +/- 11%; p less than 0.001). This worsening in mismatching of ventilation and blood flow is correlated with the enhancement in pulmonary blood flow obtained by these three therapeutic procedures.

Adult↗

Parenteral infusion with an admixture of amino acids, dextrose, and fat emulsion solution: compatibility and clinical safety.

Fat emulsions are increasingly utilized as intravenous calorie sources in patients requiring total parenteral nutrition. In the United States, they are traditionally administered separate from the dextrose/amino acid solution because of concern regarding physical stability and clinical safety when fat emulsions are administered, having been mixed with the dextrose solution. The separate infusion entails multiple manipulations of the infusion system with increased risk of contamination and sepsis and increased cost in maintaining two infusion lines. This prospective sequential two-phase clinical study evaluated solution compatibility and clinical safety of an admixture of fat emulsion (Intralipid 20%), dextrose, amino acids (Veinamine 8%), electrolytes, vitamins, and trace minerals. Continuous infusion of this solution in 25 adult patients from 2 to 35 days did not result in any adverse clinical reactions or abnormal laboratory parameters. Gross, visual examination and in vitro analysis of the admixture solutions revealed no physical instability or changes in fatty acid composition in admixture solutions stored at 4 degrees C for up to 6 weeks.

Adult↗

Stability of caffeine injection in intravenous admixtures and parenteral nutrition solutions.

Our objective was to determine the stability of caffeine base in intravenous admixtures and parenteral nutrition solutions at room temperature for 24 hours. Caffeine 10 mg/mL was used in this study. The admixtures included D5W; D5W with NaCl 0.2% injection; D5W with NaCl 0.2% and 20 mEq/L of potassium chloride injection; D10W injection; and D10W with NaCl 0.2% and 5 mEq/L of KCl injection. The parenteral nutrition solutions included 1.1% amino acids with electrolytes; 2.2% amino acids with electrolytes; and 4.25% amino acids with electrolytes. These parenteral nutrition solutions were prepared in D10W. Ten milliliters of caffeine were added to glass test tubes containing 10 mL of various solutions to yield a final concentration of 5 mg/mL. One milliliter aliquots were removed at 0, 2, 4, 8, and 24 hours and caffeine was measured by a stability-indicating HPLC method. The largest change in the concentrations of caffeine was 4.1 percent during the study period. Thus, caffeine injection is stable in various admixtures and parenteral nutrition solutions at room temperature for 24 hours.

Caffeine↗

Clinical issues regarding the use of total nutrient admixtures.

The introduction of total nutrient admixtures (TNAs) has offered several clinical advantages. Substituting a portion of the daily dextrose calories with lipids may reduce the incidence of carbohydrate-associated complications (e.g., disturbances in glucose control and immune function). In addition, providing intravenous lipids continuously over 24 hours as a TNA appears to be better utilized by the liver and less likely to interfere with reticuloendothelial system function when compared with conventionally administered, discontinuous lipid infusions. If the peripheral vein is used as a route for parenteral nutrition, the addition of fat to the admixture provides the advantage of enhancing caloric density, while contributing significantly less tonicity than dextrose. Certain pharmaceutical and microbiological issues need to be considered to ensure the intravenous administration of a safe and homogenous dispersion. Attention to established guidelines provided by the lipid manufacturers, as well as careful extrapolation of TNA stability data, will avert the dangers associated with infusion of coalesced lipid particles. This article reviews the evidence supporting the use of lipids as daily caloric sources, with particular emphasis on the role of the total nutrient admixtures as the primary vehicle for administration.

Chemistry, Pharmaceutical↗

Systemic lupus erythematosus in a multi-ethnic cohort (LUMINA) XXXII: [corrected] contributions of admixture and socioeconomic status to renal involvement.

Renal involvement in systemic lupus erythematosus (SLE) is more frequent in minorities. We examined whether genetic or socioeconomic status (SES) explain these disparities in a large multiethnic (Hispanics from Texas and Puerto Rico, African Americans and Caucasians) SLE cohort. Renal involvement was defined as WHO Class II-V and/or proteinuria (> 0.5 g/24 h or 3+) attributable to SLE and/or abnormal urinary sediment, proteinuria 2+, elevated serum creatinine/ decreased creatinine clearance twice, 6 months apart present any time over the course of the disease. Ancestry informative markers (AIMS) were used to define the admixture proportions in each patient and group. Logistic regression models were examined to determine the percentage variance (R2) in renal involvement related to ethnicity that is explained by socio-economic status (SES) and admixture (adjusting for age, gender and disease duration, basic model). Four-hundred and fifty-nine (out of 575) patients were included; renal involvement occurred in 44.6% Texas Hispanics, 11.3% Puerto Rico Hispanics, 45.8% African Americans, 18.3% Caucasians. SES accounted for 14.5% of the variance due to ethnicity (after adjusting for basic model variables), admixture 36.8% and both, 12.2%; 45.9% of the variance remained unexplained. Alternative models for decreased glomerula filtration rate and end-stage renal disease were comparable in the distribution of the explanatory variables. Our data indicate that genetic factors appear to be more important than SES in explaining the ethnic disparities in the occurrence of renal involvement.

Adult↗

Local anesthetics and pulmonary venous admixture in pregnant and nonpregnant sheep.

Pulmonary venous admixture (Qs/Qt) was determined in nine nonpregnant sheep and in seven pregnant sheep during their last trimesters of gestation. Pulmonary venous admixture was greater in the pregnant animals (5.7 +/- 1.6% of the cardiac output; mean +/- SD) than in the nonpregnant ones (4.2 +/- 1.3%; p less than 0.05). On consecutive days, four local anesthetics were infused in random order via a femoral venous catheter into each sheep for 30 minutes. Total doses of 1.8 mg/kg of bupivacaine, 2.7 mg/kg of etidocaine, 6 mg/kg of lidocaine, and 15 mg/kg or chloroprocaine were administered. None of the anesthetics induced a significant change in pulmonary venous admixture.

Anesthetics, Local↗

Comparison between clonidine and epinephrine admixture to lidocaine in brachial plexus block.

The admixture of clonidine or epinephrine to lidocaine for brachial plexus block was studied with regard to duration of block, postoperative analgesia, and plasma concentrations of lidocaine. Thirty-three patients of ASA physical status I and II received an admixture of either clonidine (150 micrograms; n = 15) or epinephrine (200 micrograms; n = 18) to 40 mL of 1% lidocaine in a randomized, double-blind fashion. Bone surgery predominated in those patients receiving clonidine and soft-tissue surgery in those receiving epinephrine (P less than 0.05). Onset and duration of block were not different between the groups. With the admixture of clonidine, fewer patients were completely pain free for greater than 12 h (13.3%) and pain scores (visual analogue scale 0-10) were higher 6 h after the block (median 4; range 0-6) than with epinephrine (61.1%; median 2; range 0-7, respectively; P less than 0.05). In patients who had received clonidine, peak plasma concentrations of lidocaine were higher (10.29 +/- 2.96 mumol/L) and occurred earlier (23.7 +/- 9.3 min; mean +/- SD) than in those treated with epinephrine (6.9 +/- 1.71 mumol/L; 72.5 +/- 56.2 min; P less than 0.05). This indicates the absence of a local vasoconstrictor effect of clonidine and implies a reduced margin of safety with regard to local anesthetic toxicity. Although clonidine does not offer advantages compared with epinephrine, it may be a useful adjunct to local anesthetics in those patients in whom the administration of epinephrine is contraindicated.

Adult↗

[Effect of admixture of commercially available corticosteroid ointments and/or creams on vasoconstrictor activity].

A commonly used admixture of commercially available ointments and/or creams was selected from the prescribed sheets in our hospital, and questionnaire to dermatologists. To assess the relationship between permeability of corticosteroid through murine skin and clinical effects in human, we attempted to investigate the vasoconstrictor activity of these admixtures of topical corticosteroid by double-blind controlled study. Test samples were occluded at random on the back of 20 healthy volunteers for 4 hours. The vasoconstrictor activity of corticosteroid creams (Lidomex) alone was significantly large as compared with that of ointments alone. The vasoconstrictor activity of corticosteroid in the admixture of Lidomex ointment and urea ointments or heparinoid ointment was 1.5-2 fold significantly larger than that from ointments alone. The extent of the stability of the emulsion after mixing was related to the vasoconstrictor activity. These experiments demonstrated a close relationship between the vasoconstrictor activity of human skin and permeability of hairless mice skin. These results suggested that the vasoconstrictor activity of topical corticosteroids mixed with commercially available ointments and/or creams depends upon their physicochemical characteristics.

Adrenal Cortex Hormones↗

[Evaluation of the permeability of corticosteroid in hairless mouse and hairless micropig skin from admixture of commercially available corticosteroid ointments and/or creams].

Yucatan hairless micropig (YHMP) skin has been shown to have histology and physiologic properties similar to human skin. To assess the relationship between the permeability of corticosteroid ointments and five types of commonly used admixtures of corticosteroid through hairless mice (HM) or YHMP skin and the clinical effects in humans, we conduct by in vitro experiments using HM and YHMP skin. The permeability of corticosteroid in admixtures with urea or heparinoid ointments across HM or YHMP skin was 1.5-4-fold greater than that of corticosteroid ointments alone. HM skin was found to have faster permeability than YHMP skin, but otherwise was similar to YHMP skin. These experiments demonstrated a close relationship between the permeability of HM or YHMP skin and vasoconstrictor activity in humans. These results suggest that the in vitro permeability of corticosteroid measurements across HM skin could be a useful, rapid, and easy method for assessing the vasoconstrictor activity of topical corticosteroids and the admixtures of commercially available ointments and/or creams in humans.

Adrenal Cortex Hormones↗

Stability of cyclophosphamide and mesna admixtures in polyethylene infusion bags.

BACKGROUND: Cyclophosphamide (CYP) is used to treat cancers in combination with mesna to prevent cystitis. The use of extemporaneously prepared admixtures of these drugs must be supported by documentation of their chemical stability. OBJECTIVE: To evaluate the chemical stability of CYP and mesna admixtures in dextrose 5% polyethylene infusion bags. METHODS: The drugs were diluted in 100-mL dextrose 5% infusion bags to final concentrations of CYP 10.8 mg/mL with mesna 3.2 mg/mL (solution A) and CYP 1.8 mg/mL with mesna 0.54 mg/mL (solution B). Six infusion bags from each solution were stored at 4 degrees C and 6 were stored at room temperature. Triplicate HPLC determinations were performed on each bag to measure drug concentrations at 0, 1, 2, 4, 6, 12, 24, 48, and 96 hours. RESULTS: At 96 hours, drug concentrations in all solutions stored at room temperature were found to be <80% compared with the initial concentrations. The solutions stored at 4 degrees C retained at least 90% of the initial drug concentrations at 48 hours. The pH of solutions A and B stored at room temperature decreased significantly by 4.44 and 4.31 units, respectively. The pH of the refrigerated infusion bags decreased significantly by 1.46 units for solution B. CONCLUSIONS: Admixtures stored at 4 degrees C (pH 7.90 +/- 0.004; mean +/- SD) are stable for 48 hours. The CYP and mesna combination can be infused at room temperature over 6 hours without significant degradation of the drugs. Stabilities are dependent on pH, temperature, and/or concentration.

Cyclophosphamide↗

I.V. admixture contamination rates: traditional practice site versus a class 1000 cleanroom.

PURPOSE: The contamination rates associated with the preparation of medium-risk i.v. admixtures in a traditional practice site and in a class 1000 cleanroom were compared. METHODS: Simulated product media fills served as the samples. Each investigator, a pharmacist and a pharmacy technician, prepared 500 vials and 500 small-volume parenteral (SVP) bags in five separate runs at a traditional practice site and in a cleanroom. United States Pharmacopeia chapter 797 medium-risk compounding procedures were followed, and strict adherence to aseptic technique was employed. Single-strength tryptic soy broth was substituted for the drug and diluent in the admixtures. Positive and negative controls were also prepared and stored for the duration of the study. The pharmacist and technician prepared a total of 4057 samples: 2027 samples (1014 vials and 1013 SVP bags) were prepared in a class 1000 cleanroom, and 2030 (1014 vials and 1016 SVP bags) were prepared at a traditional practice site. RESULTS: Contamination rates did not significantly differ between the traditional practice site (0.296%) and the cleanroom environment (0.344%) (p = 1.0). A significant difference in the number of contaminated samples was found between the two investigators (2 of 2057 were contaminated by the pharmacist and 11 of 2000 were contaminated by the technician) (p = 0.012). Contamination rates by the pharmacist (p = 1.0) and technician (p = 1.0) did not significantly differ between sites. CONCLUSION: The most important variable affecting microbial contamination of admixtures was the aseptic technique of personnel, not the environment in which the drugs were compounded.

Asepsis↗

Review of the justification for pharmacy parenteral admixture preparation.

Pharmacy-based intravenous admixture programs are still not present in many hospitals today, despite the length of time these programs have been advocated. This paper reviews the scientific, legal, and administrative basis for pharmacy-based centralized intravenous admixture programs. Key elements in developing admixture programs based on these points are reviewed.

Drug Compounding↗

Microwave thawing of frozen minibag admixtures.

An efficient system is described for the preparation of high volume minibag admixtures e.g. cefazolin. The system includes use of bulk reconstitution, freezing and microwave thawing techniques; special admixture dosage forms; and, the use of technical staff. The system can be utilized in any centralized, intravenous, admixture service where the workload is demanding for existing staff.

Cefazolin↗

Comprehensive intravenous admixture services: logistics and quality assurance in a university affiliated teaching institution.

The role of supportive personnel, as well as the supervision of intravenous (IV) admixture compounding by staff pharmacists, should be clearly identified by the departmental manager. In doing so, the department should strive to achieve an optimal mix of professional and technical personnel with automated technology. Close attention must be paid to quality assurance in order to maintain the highest quality parenteral admixture. The logistics of comprehensive IV admixture services are described for a university affiliated teaching institution. Emphasis is made on a three-faceted approach to quality assurance, including technician training, end-product testing, and equipment maintenance.

Drug Compounding↗

Evaluation of gentamicin premixed admixtures: cost and clinical utility.

An objective of this study was to evaluate the cost effectiveness of employing gentamicin premixed admixtures compared to using exact, individualized compounded doses. Gentamicin use and waste data were collected over a 2-month period. Annualized institutional savings (300 beds) were projected to be $8,802. A second objective was to compare predicted to measured peak and trough serum gentamicin concentrations when premixed admixtures are used (rounding off computer generated doses to the nearest 10 mg) and when individually compounded exact doses are delivered. Twenty adults were randomized to receive premixed or compounded doses. Blood levels drawn at steady state were compared to predicted levels for the delivered dose. Differences between measured and predicted levels were not significant by performance of an independent t test on the mean square prediction errors. We conclude that it is cost effective and clinically valid to employ premixed intravenous admixtures in a large teaching hospital.

Adult↗

Population evolution in 20th-century Easter Island: endogamy and admixture.

We studied the 20th-century evolution of the Rapanui population of Easter Island, the most geographically isolated in the world, to analyze the current process of admixture. Using parochial birth records, we determined origin of the birth parents based on their surnames. The origin of parents reveals two stages of population evolution: endogamy, due to the isolation of the island, but with a strong rejection of isonymous marriages; and admixture, beginning in 1965 with the opening of the island to the rest of the world. We used Lasker's coefficient (Lasker's Ri) and the Shannon-Weaver coefficient of diversity (H) to characterize both stages. The gene flow evaluated from admixture has increased significantly since 1965. Births from exogamous unions represented 3.5% of total births from 1937 to 1965. increased to 43.2% between 1966 and 1980, and constituted 50.8% of all births between 1981 and 1996.

Birth Rate↗

Polyomavirus JC genotypes in an urban United States population reflect the history of African origin and genetic admixture in modern African Americans.

The human polyomavirus JC (JC virus), a small, circular, double-stranded DNA virus, has a worldwide distribution and is excreted harmlessly in urine by 20% to 70% of adults. DNA sequence analysis has identified seven distinct genotypes that likely coevolved with modern humans, although the mode of virus transmission is unknown. Type 1 is European in its distribution. Types 2 and 7 are Asian, while Types 3 and 6 are African. Type 4, closely related to Type 1, is of uncertain origin, having been found in population groups in parts of Europe and in the United States, but not in Africa. Here we have studied the JCV partial genomic DNA sequences amplified by polymerase chain reaction techniques from urines of an urban, mainly African American population cohort from Washington, D.C. The predominant genotype identified was Type 4 (32/78 JCV strains, 41%). Type 1 strain was found in 32% of African Americans, while JCV Type 3 strain was found in 18% of African Americans. These African strains have persisted in modern African Americans after 200 to 400 years of minority existence and genetic admixture in the New World. An ancient West African genotype, Type 6, was absent in this African American cohort. However, one Type 6 strain was found in a patient from Sierra Leone (West Africa), domiciled in the United States for 20 years. Type 2A, the most common subtype in Native Americans, was seen in only two African-Americans (3%). A Type 7 strain, previously reported only in Taiwan and South China, was identified in a Vietnamese immigrant. These data support the history of African origin, migration, and genetic admixture of modern African Americans. Analysis of JCV strains in the present American populations provides a novel tool for reconstructing human migrations and genetic admixture in the New World.

Adolescent↗

Admixture effects in the traditional linkage analysis of admixed families.

INTRODUCTION: Families of admixed ancestry are routinely excluded from traditional linkage analysis (LOD score) or are analyzed as deriving from a homogeneous population of the proband's ethnicity. Using traditional linkage analysis methods to analyze these families is complicated due to the admixture of different disease rates and allele frequencies that occurs. The presence of admixture violates the key assumptions of Hardy-Weinberg equilibrium (HWE) and linkage equilibrium (LE) invoked in the current methods of linkage analysis. If one or both of these assumptions are violated, incorrect inference for linkage could result. DESIGN AND METHODS: We propose a pooling procedure to correct for inflated estimates of the recombination fraction that can result from admixture when performing traditional linkage analysis. Data were simulated with 30 families per each of 200 replications for a dominant, highly selective, linked disease locus model in order to conduct further testing for allelic LE and HWE, while using an allele pooling procedure to account for allele frequency differences between the 2 populations. The differences in allele frequencies between the populations for the polymorphic loci were 0.05, 0.10 and 0.14. RESULTS AND CONCLUSIONS: Our pooling procedure does not eradicate all disequilibrium, because those replicates in which the disequilibrium exists are no longer affected by the disequilibrium in terms of maximization for linkage. Furthermore, our pooling procedure was able to exclude uninformative families or families far removed from HWE and/or LE that their LOD scores were unreliable.

Alleles↗