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PubMed1992

Etoposide plus carboplatin admixture. Phase I study of five- or seven-day continuous infusion.

Thirty-five patients were entered in a Phase I trial of an admixture infusion of etoposide (VP-16) and carboplatin (CBDCA) administered continuously for 5 or 7 days. Because of the compatibility and solubility of the two agents, the treatment program could be administered on an outpatient basis. The dose rate of VP-16 was fixed at 30 mg/m2/day (total dose 150 mg/m2 for 5 days or 210 mg/m2 for seven days) for each cycle. Carboplatin was evaluated at three dose rates: 50, 60, and 75 mg/m2/day on the 5-day infusion and 40, 50, and 60 mg/m2/day on the 7-day infusion with cycles repeated at 28 to 42 days. The dose limiting toxicity was hematologic and followed a pattern typical for carboplatin, that is, delayed neutropenia and/or thrombocytopenia with a protracted leukocyte recovery. Renal toxicity was observed in three patients. The optimum total dose for the infusional carboplatin component was 300 mg/m2 (5-day) and 420 mg/m2 (7-day). The total etoposide dose was 150 mg/M2 and 210 mg/M2, which did not appear to contribute to the hematologic toxicity. Delivery of the admixture of VP-16 and CBDCA was feasible, although cumbersome, as a result of the portable delivery system. Extending the duration of infusion increases the total cumulative dose of carboplatin and etoposide that can be administered without increasing adverse effects.

Aged↗

PubMed1980

Influence of varying inspired oxygen tensions on the pulmonary venous admixture (shunt) of mechanically ventilated patients.

Pulmonary venous admixture (shunt) was measured in 10 mechanically ventilated patients with respiratory failure at varying oxygen tensions. All patients manifested a drop in pulmonary shunt as FIO2 was increased from 0.21 to 0.4. Further increase in FIO2 led to a gradual increase in the calculated venous admixture. The clinical significance of the conventional measurements of pulmonary shunt at FIO2 = 1.0 is questionable because of the marked effect of FIO2 on pulmonary shunt. Consequently, shunt measurements should be performed with the clinically useful FIO2.

Humans↗

PubMed1980

Pulmonary venous admixture during mechanical ventilation with varying FIO2 and PEEP.

Many authors have indicated that high FIO2 (0.75-1.0) ventilation may increase pulmonary venous admixture. Reabsorption atelectasis is supposedly responsible for this adverse effect. The authors attempted to determine if increasing PEEP during high FIO2 ventilation could eliminate the detrimental influence of the latter. In 17 patients in respiratory failure, hemodynamic and respiratory variables were measured during ventilation with FIO2 0.50, 0.75, and 1.0 and PEEP varying from -3 to +5 cm H2O from baseline. Before exposure to FIO2 > 0.75, addition of PEEP resulted in a decrease of Qs/Qt from a mean of 26.6-21.9%. After exposure to FIO2 0.75-1.0, Qs/Qt remained at levels not different from baseline, even when PEEP 8 cm H2O above baseline was added. The authors conclude that ventilation with high FIO2 is not useful in determining Qs/Qt, and may prevent the improvement in pulmonary venous admixture associated with PEEP therapy.

Blood Gas Analysis↗

PubMed1992

Prostacyclin (not nitroprusside) preserves venous admixture in the injured canine lung.

OBJECTIVE: To compare the effects of a prostaglandin vasodilator (prostaglandin I2 [PGI2]) with that of sodium nitroprusside in the isolated lung during 3% and 35% oxygen ventilation. BACKGROUND AND METHODS: Pulmonary vascular resistance was divided into arterial, middle, and venous segmental resistances. Left lower lobes were injured in a patchy (atelectasis) or diffuse (oleic acid-induced edema) manner. RESULTS: Nitroprusside diminished, but PGI2 ablated, the usual increase in middle segment resistance observed during 3% oxygen ventilation in atelectatic lobes. In the oleic acid-treated lobes, both nitroprusside and PGI2 ablated the increase in middle segment resistance during 3% oxygen ventilation. During nitroprusside administration, as pulmonary vascular resistance decreased, venous admixture proportionately increased, but this correlation was lost during PGI2 administration. CONCLUSIONS: We hypothesize that exogenous PGI2 dilates the vessels most constricted by hypoxia but to a lesser degree than does nitroprusside. Therefore, increases in venous admixture may be reduced during PGI2 administration, compared with nitroprusside administration.

Animals↗

PubMed2000

Admixture with whole blood does not explain false-negative urease tests.

Rapid urease test sensitivity for Helicobacter pylori is reduced in the presence of active upper gastrointestinal bleeding. The aim of this study was to evaluate the in vitro effect of whole blood on rapid urease testing. Urease solution was added to normal saline, and heparinized whole blood both positive and negative for H. pylori antibody. The mixtures were then serially diluted in saline, and/or whole blood and added to three different rapid urease kits. The admixture of urease in H. pylori-seropositive whole blood diluted in either saline or whole blood enhanced performance in both kits fourfold compared with saline alone. No false-negative results were observed in either kit. Seronegative whole blood produced similar results. Undiluted saline or whole blood produced no positive rapid urease tests. Whole blood accelerates the urease reaction in vitro. Neither H. pylori antibody-positive nor -negative whole blood adversely impacted the rapid urease test. False-negative rapid urease test results in upper gastrointestinal bleeding cannot be explained by admixture with whole blood.

Clinical Enzyme Tests↗

PubMed1993

In vitro comparison of heated saline-blood admixture with a heat exchanger for rapid warming of red blood cells.

We compared the rapidity of rewarming and infusing red blood cells (RBCs) mixed with 24 degrees C, 50 degrees C, and 60 degrees C saline with the rapidity of administering undiluted RBCs through a heat exchanger. We measured flow rate, final temperature, and hemolysis in matched 41-45-day-old pooled AS-1 RBCs infused through high-flow tubing via a 14-gauge catheter under the influence of gravity. Undiluted RBCs were tested as controls. The final temperature of the 60 degrees C admixture technique was lower than that with the heat exchanger (28.5 +/- 0.2 degrees C vs. 32.7 +/- 0.2 degrees C), but the flow rate was higher (258 +/- 8 mL/min vs. 61 +/- 4 mL/min). Admixture with 60 degrees C saline resulted in no increase in hemolysis. This technique appears to be a simple, inexpensive method for rapid rewarming and infusion of RBCs and may be valuable for administration of RBCs simultaneously through multiple sites during resuscitation.

Erythrocyte Transfusion↗

PubMed1998

Basic principles for compounding all-in-one parenteral nutrition admixtures.

Parenteral nutrition admixtures are complex pharmaceutical entities. The more closely they are examined, the more physico-chemical interactions emerge that could potentially affect stability. The move towards large scale hospital or commercial preparation, with a requirement for extended shelf life, and the increasing use of admixtures as vehicles for drugs and pharmaconutrients have created new formulation challenges for pharmaceutical scientists.

Chemical Phenomena↗

PubMed2005

Will admixture mapping work to find disease genes?

Admixture mapping is the first experimentally practical method for carrying out a whole-genome association scan, and is thus a promising method for detecting risk factors for common disease. The goal of the community should now be to aggressively test whether the method is useful in practice for localizing disease genes, by carrying out at least three high-powered studies. We also propose a stringent criteria we believe the community should adopt before declaring a statistically significant admixture association to disease.

Chromosome Mapping↗

PubMed2004

Stability of an epidural analgesic admixture containing epinephrine, fentanyl and bupivacaine.

The addition of epinephrine to solutions containing fentanyl and bupivacaine for epidural infusion has been shown to improve the quality of analgesia. However, this admixture is not available commercially in the United Kingdom. Moreover, stability data applicable to UK practice for this admixture are limited. This study investigated the stability of fentanyl 2 microg.ml(-1) plus bupivacaine 1 mg.ml(-1) in PVC bags with and without epinephrine 2 microg.ml(-1) over a period of 184 days both at room temperature and at 4 degrees C. All infusions were found to be stable over the study period (> 90% remaining) using stability-indicating High Performance Liquid Chromatography (HPLC) methods, with no changes in physical appearance or pH (range 4.5-4.2). The infusions were prepared using standard pharmaceutical products, so facilitating the batch preparation of epinephrine, fentanyl and bupivacaine epidural solutions by hospital pharmacy departments.

Analgesia, Epidural↗

PubMed2006

Combination of multiple microsatellite data sets to investigate genetic diversity and admixture of domestic cattle.

Microsatellite markers are commonly used for population genetic analyses of livestock. However, up to now, combinations of microsatellite data sets or comparison of population genetic parameters from different studies and breeds has proven difficult. Often different genotyping methods have been employed, preventing standardization of microsatellite allele calling. In other cases different sets of markers have been genotyped, providing differing estimates of population genetic parameters. Here, we address these issues and illustrate a general two-step regression approach in cattle using three different sets of microsatellite data, to combine population genetics estimates of diversity and admixture. This regression-based method is independent of the loci genotyped but requires common breeds in the data sets. We show that combining microsatellite data sets can provide new insights on the origin and geographical distribution of genetic diversity and admixture in cattle, which will facilitate global management of this livestock species.

Animals↗

PubMed1983

Evaluation of drug contamination levels in an admixture preparation area.

The risks of drug contamination after transfer manipulations between vials used in admixture preparations were estimated. The transfers were performed inside a safety cabinet using sodium pertechnetate 99Tcm in saline as a 'model' admixture. An air contamination monitor was attached to the safety cabinet above the transfer manipulation area. The monitor filter and all utensils used were collected for measurement of contamination levels in each sample trial. Three types of transfer were performed; one 'open' procedure and two 'closed' procedures, one including an air vent needle in the receiving vial and the other without air vent needle in the receiving vial. The closed procedure including an air vent needle appears to combine good personnel- and product protection.

Air Pollutants, Occupational↗

PubMed1994

Influence of background air on microbial contamination during simulated i.v.-admixture preparation.

The effect of the cleanliness of environmental air on the microbial contamination of a simulated i.v.-admixture during its preparation by aseptic transfer was studied under three conditions: (i) in a laminar air flow (LAF) bench situated in a class 1000 clean room, (ii) in an LAF bench in a microbiology laboratory and (iii) on a bench in an ordinary laboratory. Three thousand bottles were manually filled with 10 ml of a nutrient broth under each of the three conditions. The liquid was transferred by means of a syringe and a needle that pierced through the rubber closures of the bottles. The numbers of contaminated bottles under those three conditions were 1, 1 and 2, respectively. Background contamination had no demonstrable effect on the incidence of contamination, provided that preparation of the simulated i.v.-admixture solution was performed by skilled personnel in an LAF cabinet and air contact is avoided.

Air Pollution, Indoor↗

PubMed2006

Detecting introgressive hybridization between free-ranging domestic dogs and wild wolves (Canis lupus) by admixture linkage disequilibrium analysis.

Occasional crossbreeding between free-ranging domestic dogs and wild wolves (Canis lupus) has been detected in some European countries by mitochondrial DNA sequencing and genotyping unlinked microsatellite loci. Maternal and unlinked genomic markers, however, might underestimate the extent of introgressive hybridization, and their impacts on the preservation of wild wolf gene pools. In this study, we genotyped 220 presumed Italian wolves, 85 dogs and 7 known hybrids at 16 microsatellites belonging to four different linkage groups (plus four unlinked microsatellites). Population clustering and individual assignments were performed using a Bayesian procedure implemented in structure 2.1, which models the gametic disequilibrium arising between linked loci during admixtures, aiming to trace hybridization events further back in time and infer the population of origin of chromosomal blocks. Results indicate that (i) linkage disequilibrium was higher in wolves than in dogs; (ii) 11 out of 220 wolves (5.0%) were likely admixed, a proportion that is significantly higher than one admixed genotype in 107 wolves found previously in a study using unlinked markers; (iii) posterior maximum-likelihood estimates of the recombination parameter r revealed that introgression in Italian wolves is not recent, but could have continued for the last 70 (+/- 20) generations, corresponding to approximately 140-210 years. Bayesian clustering showed that, despite some admixture, wolf and dog gene pools remain sharply distinct (the average proportions of membership to wolf and dog clusters were Q(w) = 0.95 and Q(d) = 0.98, respectively), suggesting that hybridization was not frequent, and that introgression in nature is counteracted by behavioural or selective constraints.

Alleles↗

PubMed2006

Genetic admixture of burbot (Teleostei: Lota lota) in Lake Constance from two European glacial refugia.

The burbot, Lota lota, is the only freshwater species of the codfish family and has a Holarctic distribution. Pleistocene glaciations caused significant geographical differentiation in the past, but its life history characterized by winter spawning migrations over large distances is likely to homogenize populations by contemporary gene flow. We investigated the population genetic structure of 541 burbots from Lake Constance and adjacent Rhine and Danube tributaries in Europe using the entire mitochondrial DNA (mtDNA) control region and 11 microsatellites. Microsatellites revealed considerable population divergence (F(ST) = 0.26) and evidenced recent bottlenecks in two Central European rivers. In accordance to previous evidence two main phylogeographic lineages (Atlantic and Danubian) were found co-occurring at similar frequencies in Lake Constance, where they currently undergo random mating as indicated by microsatellites. The Danubian lineage contributed only a small proportion to the lake's mtDNA diversity, and probably expanded within the lake shortly after its formation approximately 10,000-15,000 BP. The larger Atlantic haplotype diversity suggested a population expansion older than the lake itself. Levels of admixture at microsatellite loci were less obvious due to their high variability, and coalescence methods were used to estimate past admixture proportions. Our results reinforce a model of a two-step colonization of Europe by burbot from an ancestral Danubian refuge, and confirm the persistence of a secondary Atlantic refuge, as proposed to exist for other freshwater fish. We conclude that the present-day burbot population in Lake Constance bears the genetic signature of both contemporary gene flow and historical separation events.

Animals↗

PubMed1996

Effect of inhaled nitric oxide on venous admixture depends on cardiac output in patients with acute lung injury and acute respiratory distress syndrome.

BACKGROUND: It has been shown that inhaled nitric oxide (NO) reduces intrapulmonary venous admixture (QVA/QT) and improves oxygenation in patients suffering from acute respiratory distress syndrome (ARDS). The change in QVA/QT during NO inhalation varies individually. Factors known to influence the respiratory response to NO are the NO concentration and the level of shunt before NO administration. Other factors that may modify the effect on gas-exchange during NO breathing are unknown. METHODS: We studied the effect of 40 ppm inhaled NO on pulmonary gas-exchange and haemodynamics in 37 patients with acute lung injury (ALI) and ARDS, respectively, and factors that may influence the respiratory response to NO. RESULTS: Inhalation of 40 ppm NO produced a decrease in mean pulmonary artery pressure (MPAP) from 33.1 +/- 7.2 to 30.2 +/- 6.8 (mean +/- SD) mmHg (P < 0.0001) while pulmonary artery wedge pressure (PAWP), cardiac output and mean arterial pressure remained constant. Change in QVA/QT during NO inhalation depended on the preinhalation cardiac output and had no association with mixed venous oxygen tension, MPAP-PAWP, and QVA/QT before NO delivery. QVA/QT decreased in 26 patients (group 1) and increased in 11 patients (group 2) during NO inhalation. In group 1, cardiac output was lower than in group 2 (8.6 vs 12.2 l.min-1; P < 0.0005). CONCLUSION: We conclude that the change in venous admixture during inhalation of 40 ppm NO depends on cardiac output. If preinhalation cardiac output is high, 40 ppm NO can adversely affect gas exchange in patients with ALI and ARDS.

Acute Disease↗

PubMed1982

Evolutionary trees and admixture: phylogenetic inference when some populations are hybridized.

Maximum likelihood estimation of admixture parameters and divergence times for an evolutionary tree in which some populations may be hybridized is developed. A test of treeness against the alternative of hybridization using a hierarchy of admixture models is proposed as an adjunct to the goodness-of-fit test suggested by Cavalli-Sforza & Piazza (1975). The method is illustrated by an application to gene frequency data from Makiritare Indian villages in southern Venezuela.

Gene Frequency↗

PubMed2004

Using genetic admixture to study the biology of obesity traits and to map genes in admixed populations.

Differences among ethnic and racial groups in obesity-related traits have been clearly established in the scientific literature. To explore the genetic component underlying these differences, the genetic admixture approach has been used. In this approach, ancestry informative genetic markers are used to estimate a quantitative value representing the degree of ancestral background in individuals of admixed genetic background. Genetic admixture has been successfully used to explain racial and ethnic variation in obesity related traits; however, the understanding and measure of cultural and environmental components that also influence these phenotypes still requires further exploration.

American Indian or Alaska Native↗

PubMedDate not supplied

A unified approach to adjusting association tests for population admixture with arbitrary pedigree structure and arbitrary missing marker information.

A general approach to family-based examinations of association between marker alleles and traits is proposed. The approach is based on computing p values by comparing test statistics for association to their conditional distributions given the minimal sufficient statistic under the null hypothesis for the genetic model, sampling plan and population admixture. The approach can be applied with any test statistic, so any kind of phenotype and multi-allelic markers may be examined, and covariates may be included in analyses. By virtue of the conditioning, the approach results in correct type I error probabilities regardless of population admixture, the true genetic model and the sampling strategy. An algorithm for computing the conditional distributions is described, and the results of the algorithm for configurations of nuclear families are presented. The algorithm is applicable with all pedigree structures and all patterns of missing marker allele information.

Algorithms↗