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PubMed1992

Esmolol infusion during nitroprusside-induced hypotension: impact on hemodynamics, ventricular performance, and venous admixture.

The impact of esmolol infusion on hemodynamics, ventricular performance, venous admixture, sympathoadrenal, and renin-angiotensin system responses during sodium nitroprusside (SNP)-induced hypotension was studied in 11 patients undergoing lymph node dissection during general anesthesia with 60% nitrous oxide and fentanyl. Radial arterial and thermistor-tipped pulmonary catheters were employed for hemodynamic monitoring. Arterial and mixed venous blood gas tensions, arterial plasma renin activity (PRA), and plasma catecholamine levels were measured. Derived hemodynamic parameters and venous admixture (Qs/Qt) data were obtained from standard equations. Transesophageal echocardiography (6 patients) was used to assess left ventricular performance using the relationship between end-systolic wall stress (ESWS) and velocity of circumferential shortening (VCFC). After surgical incision, arterial hypotension was induced with SNP alone. Esmolol was infused at each of the following rates in sequence: 200, 300, and 400 micrograms/kg/min. Each esmolol infusion lasted 20 minutes and the SNP dose was adjusted to maintain MAP at 55 to 60 mm Hg. The mean dose of SNP required to induce hypotension was 5.5 micrograms/kg/min +/- 0.5 SE. Compared to prehypotension values, SNP induced significant increases in Qs/Qt and reductions in PaO2, systemic vascular resistance (SVR), and stroke volume index (SVI). Esmolol infusion caused dose-dependent (highest with 400 micrograms/kg/min) reductions in the SNP requirement, heart rate (HR), SVI, Qs/Qt, and PRA, and also led to significant increases in SVR and left ventricular (LV) internal diameter in diastole as well as systole. Furthermore, esmolol infusion was associated with a dose-dependent downward and leftward shift of the ESWS versus VCFC relationship, implying diminished contractility.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed2004

Venous flow restriction: the role of vein wall motion in venous admixture.

OBJECTIVE: There are wide differences in flow between vascular beds at rest, even more during stress. The hydrodynamic energy (Energy grade line or EGL) of venous outflows must also vary considerably between vascular beds. We explored the mechanism of venous admixture of differing energy flows using a mechanical model. MATERIALS AND METHODS: The model simulated two venous flows coalescing at a venous junction and then flowing through collapsible venous pumps. Flow rates and pressures were monitored when the venous pumps were full (steady state) and when they were compressed and allowed to refill inducing wall motion (pump flow). RESULTS: With increasing EGL differences between two coalescing venous flows, reduction or cessation (venous flow restriction) of the weaker flow occurred during steady state; higher base EGL of both flows ameliorated venous flow restriction and lower base EGL the opposite. Outflow obstruction favoured venous flow restriction. Pump action in the vicinity of the venous junction abolished venous flow restriction and maximized both venous flows. CONCLUSION: The model suggests a pivotal role for vein wall motion in venous admixture and regional perfusion. Observations in the model are explained on the basis of network flow principles and collapsible tube mechanics.

Biomechanical Phenomena↗
PubMed2004

Admixture analysis of age at onset in schizophrenia.

In schizophrenia, clinical, familial and biological characteristics according to age at onset (AAO) suggest that AAO is a valid candidate symptom for genetic studies. However, none of the various thresholds used to define AAO subgroups in schizophrenia has been validated. We aim to define different AAO subtypes by admixture analysis in a sample of prospectively recruited subjects with schizophrenia. Consecutive inpatients and outpatients (N=141) meeting DSM IV criteria for schizophrenia were included. We used admixture analysis to investigate whether the observed AAO distribution consisted of a mixture of gaussian distributions and then compared clinical features and familial risks in the various groups of subjects. The model that best fitted the observed AAO distribution was a mixture of two gaussian distributions (mean+/-S.D.): (19.91+/-3.56 years) and (33.48+/-8.2 years), with a cutoff point at 28 years. The existence of two subgroups according to AAO was further confirmed by the different clinical and familial profiles of these subgroups. The early-onset group consisted predominantly of male patients, with non-paranoid subtypes and with a higher familial risk of schizophrenia spectrum disorders and affective disorders. The late-onset group of patients presented predominantly paranoid subtype, preponderance of females; they were more likely to be married and to have children. We identified two subgroups of schizophrenic subjects with different clinical and familial profiles. This study provides a mathematical validation of the existence of two subgroups defined by an onset of schizophrenia before or after 28 years. These results may have important implications for the search for schizophrenia susceptibility factors. Working with homogeneous subgroups defined on the basis of AAO may facilitate the identification of genetic vulnerability factors in schizophrenia.

Adult↗
PubMed2004

Effect of blood admixture on in vitro survival of chilled and frozen-thawed canine spermatozoa.

Hematospermia in the dog usually occurs secondary to benign prostatic hypertrophy or trauma of the penis or prepuce during semen collection. Regarding the difficulty of removing blood cells from a hematospermic sample, the present study was performed to determine whether blood contaminated ejaculates can still be chilled (4 degrees C) or frozen (-196 degrees C) without an additional decrease in sperm quality. In the first experiment, blood additions of up to 10% exerted no negative effects on the functional characteristics of canine spermatozoa cooled (4 degrees C) and stored for 4 days in an egg-yolk-Tris extender. In contrast, in experiment 2, blood admixtures of 4% or more clearly caused negative effects on cryopreserved (-196 degrees C) spermatozoa, mainly on the motility parameters, on the membrane integrity and on the acrosomal status of the spermatozoa. In experiment 3, we showed that these negative effects of blood admixture on cryopreserved spermatozoa were mainly associated with the red blood cells (RBCs) whereas the addition of plasma, serum or inactivated serum exerted little or no negative effect. Moreover, in experiment 4, we showed that 58.3+/-11.6% of the RBCs hemolysed after a freeze-thaw process. In experiment 5, a clear and negative effect of hemoglobin on cryopreserved canine spermatozoa was observed. We conclude that the presence of up to 10% blood is not detrimental for the storage of chilled canine spermatozoa and that the detrimental effects of blood on cryopreserved spermatozoa are at least partly attributable to the high amount of hemoglobin originating from the RBC hemolysis observed after freezing and thawing.

Animals↗
PubMed2004

Genetic admixture of European FRDA genes is the cause of Friedreich ataxia in the Mexican population.

Friedreich ataxia accounts for approximately 75% of European recessive ataxia patients. Approximately 98% of pathogenic chromosomes have large expansions of a GAA triplet repeat in the FRDA gene (E alleles), and strong linkage disequilibrium among polymorphisms spanning the FRDA locus indicates a common origin for all European E alleles. In contrast, we found that only 14 of 151 (9.3%) Mexican Mestizo patients with recessive ataxia were homozygous for E alleles. Analysis of polymorphisms spanning the FRDA locus revealed that all Mestizo E alleles had the common European haplotype, indicating that they share a single origin. Genetic admixture levels were determined, which revealed that the relative contributions to the Mestizo FRDA gene pool by Native American and European genes were 76-87% and 13-24%, respectively, commensurate with the observed low prevalence of Friedreich ataxia in Mestizos. This indicates that Friedreich ataxia in Mexican Mestizos is due to genetic admixture of European mutant FRDA genes in the Native American gene pool that existed prior to contact with Europeans.

Adaptor Proteins, Signal Transducing↗
PubMed1968

A theoretical study of pulmonary capillary gas exchange and venous admixture.

A model of pulmonary capillary gas exchange and venous admixture is presented and the inclusion of this model into a model of the entire respiratory system is discussed. Partial pressure and concentration gradients for nitrogen, helium, oxygen, and carbon dioxide are predicted. The cases of breathing room air and 10% oxygen are studied. In both of these studies the Bohr and Haldane effects are included, and the "physiological" dissociation curves of oxygen and carbon dioxide are predicted for the normal case as blood flows from the venous blood end of the capillary to the arterial blood end. Venous admixture effects are also calculated for both of these cases. The effects of emphysema, pulmonary congestion, and altered cardiac function on the gradients are studied.

Capillaries↗
PubMed1998

Influence of genetic admixture on polymorphisms of drug-metabolizing enzymes: analyses of mutations on NAT2 and C gamma P2E1 genes in a mixed Hispanic population.

OBJECTIVES AND STUDY DESIGN: The genetic basis of two polymorphisms of drug- and carcinogen-metabolizing enzymes, NAT2 (arylamine N-acetyltransferase-2) and CYP2E1 (cytochrome P450 2E1), was studied in genomic deoxyribonucleic acid from 137 healthy, unrelated subjects from a mixed Nicaraguan population. RESULTS: Six point mutations were identified at the coding region of the NAT2 gene, including the most common alleles NAT2*4 (41.6%), NAT2*5B (31.4%), and NAT2*6A (16.8%). The percentage of carriers of two defective genes was 49.6%. The Nicaraguan population studied was in Hardy-Weinberg's disequilibrium for the NAT2 genotype (p < 0.01) and the allele frequencies were significantly different from those of other populations, being intermediate between those of pure Central American Indians and Spanish persons. The frequency of CYP2E1 alleles mutated at the RsaI site (c2 allele; 16.5%) was intermediate between that of Spanish white and Asian subjects. About 5% of the subjects were homozygous for the c2 allele. CONCLUSIONS: These findings indicate a high impact of genetic admixture of populations of Asian origin (Central American Indians) and white persons (Spaniards) on the genetic polymorphisms studied here and suggest that among mixed Hispanics a high heterogeneity of genotypes and phenotypes can be expected depending on the degree of genetic admixture of every subgroup. Therefore different subgroups of mixed Hispanic subjects can exhibit different results when treated with drugs that are inactivated through polymorphic enzymes.

Arylamine N-Acetyltransferase↗
PubMed1990

Determination of tebufelone (a new anti-inflammatory drug) strength and stability in bulk drug, dosage formulations and feed admixtures by reversed-phase high-performance liquid chromatography.

A rugged reversed-phase high-performance liquid chromatographic method suitable for the quantitative determination of tebufelone, a new anti-inflammatory drug, in bulk drug, various pharmaceutical formulations and animal feed admixtures is described. Tebufelone was easily separated from synthetic by-products and detected by ultraviolet absorption (280 nm). Standard curves were linear (r2 greater than 0.999) over 2 orders of magnitude with a detection limit of 0.1 microgram/ml at a signal-to-noise ratio of 2 (0.05 ml injected). Recovery of tebufelone from bulk drug and dosage formulations was greater than 99% with a coefficient of variation of 1.8% throughout the range of the standard curve. Recovery of tebufelone from feed admixtures was 96-102% with a less than 5% relative standard deviation at the levels assayed.

Alkynes↗
PubMed2002

pH-stabilization of predegraded PDLLA by an admixture of water-soluble sodiumhydrogenphosphate--results of an in vitro- and in vivo-study.

Aim of the study was to examine if the addition of buffering sodiumhydrogenphosphate to poly(D,L)lactide(PDLLA) would stabilize the pH-value in the in vivo environment of implanted material and whether this improves its biocompatibility. The material was predegraded just to the point of viscous disintegration to test the PDLLA in the moment of its most aggressive effect on the surrounding tissue. Racemic amorphous PDLLA was injection-molded with or without the admixture of 1 mol NaP per 100 mol lactate, the degradation product of PDLLA (=1 mol%) to form 20mm x 3 mm x 2mm rods. Predegradation was performed by storing the rods at 55 degrees C for 14 days, just to the point of beginning dissolution. Predegraded PDLLA or PDLLA + NaP samples were used for in vitro incubation tests, as well as for the in vivo study, where the rods were implanted into the spinal muscles of 30 male Wistar rats. Repeatedly, measurements of the pH-value were made in the incubation solutions in vitro. The surrounding tissue of the implanted samples as well as the normal contralateral muscle tissue was checked for its pH-value in a group of 3 rats, respectively, anaesthesized at various time intervals after implantation. After these measurements the implants and their surrounding tissues were excised for histological examination. In Ringer's solution pH-values dropped immediately within the first week of incubation of both predegraded materials reaching -4 pH units after 4 weeks in the PDLLA containing medium, after 6 weeks in the PDLLA + NaP containing medium. Soerensen buffer slowed the pH decrease with significant differences between the material groups up to the 28th week. In vivo, the pH of the surrounding tissue was influenced by the implanted PDLLA material up to the 4th week, while the admixture of NaP resulted in a significant pH stabilization. A higher quantity of macrophages and giant cells were seen between the 2nd and 6th week after the implantation in the environment of pure PDLLA compared with PDLLA + NaP. Complete resorption of predegraded pure PDLLA or PDLLA + NaP from the extracellular space was reached 28 weeks postimplantation in vivo. Thus, sodiumhydrogenphosphate improves the biocompatibility of degrading PDLLA at the point of viscous disintegration by stabilizing the pH-value in the environment of the implants for several weeks and reducing adverse tissue reactions.

Animals↗
PubMedDate not supplied

Stability and compatibility of admixtures of intravenous ciprofloxacin and selected drugs.

The stability and compatibility of ciprofloxacin with selected drugs in intravenous admixtures were studied. Ciprofloxacin 2 mg/mL in 5% dextrose was combined with each of 22 other drugs at concentrations commonly used in clinical practice. Each combination was maintained at room temperature (approximately 22 degrees C) in constant fluorescent light. Immediately after preparation and at 6 and 24 hours, each admixture was examined visually in normal fluorescent room light and the pH value was determined. For samples lacking visible precipitates or having pH changes of not more than 1 unit, ciprofloxacin concentration was assayed by using high-performance liquid chromatography. When combined with ciprofloxacin, 14 of the study drugs did not alter the concentration of ciprofloxacin, including amikacin sulfate, atracurium besylate, aztreonam, cimetidine hydrochloride, dobutamine hydrochloride, fluconazole, gentamicin sulfate, metronidazole (intravenous, ready to use), midazolam hydrochloride, norepinephrine bitartrate, pancuronium bromide, potassium chloride, tobramycin sulfate, and vecuronium bromide. There were five drugs that were determined to be incompatible with ciprofloxacin because of precipitate formation (amphotericin B, ampicillin sodium/sulbactam sodium, cefuroxime sodium, piperacillin sodium, and sodium bicarbonate). Incompatibility with ciprofloxacin based on pH changes of more than 1 unit was found with four drugs: ampicillin sodium/sulbactam sodium, ceftazidime, metronidazole hydrochloride (powder only), and ticarcillin disodium/clavulanate potassium. Intravenous ciprofloxacin 2 mg/mL admixed in 5% dextrose was stable and compatible with 14 of the 22 test drugs for up to 24 hours at room temperature. The other eight drugs should not be combined with ciprofloxacin.

Amphotericin B↗
PubMed2003

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↗
PubMed2001

Quantitative analysis of metronidazole in intravenous admixture with ciprofloxacin by first derivative spectrophotometry.

Metronidazole in parenteral admixture with ciprofloxacin was analysed by first-derivative spectrophotometry using the zero-crossing technique of measurement. The procedure did not require prior separation steps. The method was found to be linear (r(2)>0.999) in the range of 2.5-10 microg ml(-1) for metronidazole in absence or presence (at constant concentration) of ciprofloxacin. The first-derivative method was applied for the analysis of intravenous admixture of metronidazole and ciprofloxacin and proved to be rapid, accurate and reproducible.

Anti-Infective Agents↗
PubMed2003

Stability and compatibility of morphine-clonidine admixtures in an implantable infusion system.

Nonopioid analgesics are often coadministered with intrathecal morphine to increase efficacy. The purpose of this study was to evaluate stability and compatibility of morphine-clonidine admixtures with an implantable infusion system that is commonly used to treat pain patients. Infusion systems were filled with admixture and maintained at 37 degrees C for 90 days. Samples were collected monthly. Drug concentrations were determined using stability-indicating, high-performance liquid chromatography. For compatibility testing, individual materials comprising the fluid pathway of the device were immersed in clonidine solution and stored at 37 degrees C for various periods through 64 weeks and mechanical performance evaluated. After 3 months of containment in the infusion system, morphine and clonidine concentrations remained at > or = 94% of the theoretical starting concentrations. All device materials retained acceptable mechanical performance following clonidine exposure. These results demonstrate that morphine and clonidine are stable when combined in aqueous solution maintained at body temperature in an implantable infusion system for at least 3 months.

Analgesics↗
PubMed2003

Stability of total nutrient admixtures in reference to ambient temperatures.

OBJECTIVE: To evaluate the stability of emulsions under different temperatures simulating clinical conditions of storage and exposure during infusion, five total nutrient admixture formulas in this institution were analyzed: adult, patients with hepatic failure, infants, stressed patients, and patients with renal failure. METHODS: Each mixture was allocated in a sterile 100-mL glass bottle, which was prefilled and refilled with nitrogen gas. Bottles were stored at 4 degrees C for 0 d, 3 d, and 7 d and then exposed to three different temperatures: usual room temperature (18 degrees C to 25 degrees C), high (>28 degrees C) in a water bath, or storage (4 degrees C) for 24 and 48 h. The gross inspection of the emulsions and parallel measurements of pH, particle sizes, divalent ions, peroxide levels, and microbial cultures were performed. RESULTS: Every lot was stable near 18 degrees C, but 8 of 10 lots stored for 7 d (25 degrees C and >28 degrees C) and 15 of 20 lots stored for 3 and 7 d (25 degrees C and >28 degrees C) showed coalescence. The overall coalescence incidences by storage, exposure, and heat were statistically significant (P < 0.005). CONCLUSION: For the safety of total nutrient admixtures, special attention is required to keep the ambient temperature below 28 degrees C and completely exclude air from the container.

Adult↗
PubMed1997

In vitro oxidation of i.v. lipid emulsions in different all-in-one admixture bags assessed by an iodometric assay and gas-liquid chromatography.

Polyunsaturated fatty acids (FAs) of intravenous (IV) lipid emulsions can peroxidize to potentially harmful lipid hydroperoxides. In order to assess in vitro peroxidation of IV fat emulsions in all-in-one (AIO) admixture bags, an iodometric titration to determine lipid hydroperoxide content expressed by the peroxide value (PV) and a gas-liquid chromatographic (GLC) assay to determine changes of the FA pattern were established. A long-chain triglyceride (LCT) and medium-chain triglyceride-LCT emulsion were compared for the PV and the pH during storage at room temperature and daylight in AIO bags made of ethylvinylacetate (EVA) and polypropylene:polyamide 7:3 (V90). In contrast to storage in glass bottles, significant peroxidation was detected in both emulsions with 0.5-3.4 mmol peroxides/L after 28 d (150 times the control PV). A pH drop of at least 0.3 (EVA) and 1.2 (V90) units was measured. Initial PVs and peroxidation kinetics of the emulsions were different; V90 material showed better barrier properties against oxygen. PV was increased by higher temperature and light exposure. The FA pattern of an LCT emulsion with a PV > 6 (storage: 40 degrees C in a dark room for 28 d in AIO bags) assayed by GLC remained unchanged. The iodometric peroxide and the GLC assay were reproducible and easy to handle. Only the iodometric method was sensitive enough to detect peroxidation effects (detection limit: 0.02 mmol peroxides/L). IV fat emulsions can be checked for lipid hydroperoxide content with the rapid iodometric assay to guarantee optimal quality of IV lipids used for AIO admixtures. To prevent peroxidation, lipids in AIO bags should be stored light-protected in a refrigerator an oxygen-tight overwrap is mandatory for extended periods.

Chromatography, Gas↗
PubMed2000

Estimation of admixture and detection of linkage in admixed populations by a Bayesian approach: application to African-American populations.

We describe a novel method for analysis of marker genotype data from admixed populations, based on a hybrid of Bayesian and frequentist approaches in which the posterior distribution is generated by Markov chain simulation and score tests are obtained from the missing-data likelihood. We analysed data on unrelated individuals from eight African-American populations, genotyped at ten marker loci of which two (FY and AT3) are linked (22 cM apart). Linkage between these two loci was detected by testing for association of ancestry conditional on parental admixture. The strength of this association was consistent with European gene flow into the African-American population between five and nine generations ago. To mimic the mapping of an unknown gene in an 'affecteds- only' analysis, a binary trait was constructed from the genotype at the AT3 locus and a score test was shown to detect linkage of this 'trait' with the FY locus. Mis-specification of the ancestry-specific allele frequencies - the probabilities of each allelic state given the ancestry of the allele - was detected at three of the ten marker loci. The methods described here have wide application to the analysis of data from admixed populations, allowing the effects of linkage and population structure (variation of admixture between individuals) to be distinguished. With more markers and a more complex statistical model, genes underlying ethnic differences in disease risk could be mapped by this approach.

Bayes Theorem↗
PubMedDate not supplied

What causes birth order-intelligence patterns? The admixture hypothesis, revived.

Recent evidence shows that the relation between birth order and intelligence is not the same in cross-sectional and within-family data. This simple empirical observation invalidates the conclusions from hundreds of previous birth order studies that relied on cross-sectional data. Simultaneously, the empirical foundation disappears from underneath theories like dilution and the confluence model that use explanatory processes occurring within the family. A theory proposed almost 25 years ago--the admixture hypothesis--effectively accounts for these empirical patterns. In this article, the author describes why birth order is of such intense interest to both parents and researchers (the birth order trap), discusses past birth order-intelligence patterns, shows that the admixture hypothesis accounts for those patterns, and reframes the original argument to support future productive research efforts.

Birth Order↗
PubMed2005

Admixture mapping for hypertension loci with genome-scan markers.

Identification of genetic variants that contribute to risk of hypertension is challenging. As a complement to linkage and candidate gene association studies, we carried out admixture mapping using genome-scan microsatellite markers among the African American participants in the US National Heart, Lung, and Blood Institute's Family Blood Pressure Program. This population was assumed to have experienced recent admixture from ancestral groups originating in Africa and Europe. We used a set of unrelated individuals from Nigeria to represent the African ancestral population and used the European Americans in the Family Blood Pressure Program to provide estimates of allele frequencies for the European ancestors. We genotyped a common set of 269 microsatellite markers in the three groups at the same laboratory. The distribution of marker location-specific African ancestry, based on multipoint analysis, was shifted upward in hypertensive cases versus normotensive controls, consistent with linkage to genes conferring susceptibility. This shift was largely due to a small number of loci, including five adjacent markers on chromosome 6q and two on chromosome 21q. These results suggest that chromosome 6q24 and 21q21 may contain genes influencing risk of hypertension in African Americans.

Black People↗