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Admixture analysis of high density lipoprotein cholesterol distribution in a Jerusalem population sample.

The distribution of high density lipoprotein cholesterol values (HDL-C) in 2003 nuclear families (including both parents and one child aged 17) participating in the Jerusalem Lipid Research Clinic survey, were analyzed by a maximum-likelihood procedure for evidence of bimodality. HDL-C was age-sex adjusted by the mean-variance method to 17 year old male levels. After covariance adjustment for Quetelet's index, season, education and social class, when using untransformed data a mixture of two distributions fitted the data significantly better than one distribution in both sexes. The results indicated that 4.7% of males and 14.1% of females came from an upper distribution with mean values of 2.15-3.15 standard deviations above the major mode. We next applied the MacLean et al. (1976) method of transformation and used a maximum-likelihood method in which the skewness parameter was estimated jointly with the other parameters of the model. When the data were transformed the mixture of two distributions fitted the data significantly better than one for males only. We tested a mixture of three normal distributions and estimated that 6% of both males and females belonged to a higher distribution, while 1% came from a lower distribution. This model did not provide a significantly better fit to the data than a mixture of two distributions. Our findings imply that in the Israeli population there is evidence for an admixture in the distribution of HDL-cholesterol. Segregation analysis is necessary in order to determine whether a major gene or some environmental factors are responsible for the commingling detected.

Adolescent↗

Oxygen transport and venous admixture in the extremely obese. Influence of anaesthesia and artificial ventilation with and without positive end-expiratory pressure.

Eight extremely obese patients (mean weight 136 kg) were studied when awake and breathing air, and during anaesthesia with controlled ventilation (oxygen fraction in inspirate (FIO2): 0.5). During anaesthesia, the atients were first studied with zero end-expiratory pressure (ZEEP) ventilation. Then two different positive end-expiratory pressures (PEEP) were applied, 10 cmH2O and 15 cmH2O, in order to study the effect of an increase in functional residual capacity (FRC). Arterial oxygenation and oxygen availability, as well as cardiac output (QT) and venous admixture (QS/QT) were studied. With the institution of anaesthesia and ZEEP, the alveolar arterial oxygen tension difference (P(A-a)O2) rose from 3.5 +/- 1.1 to 28.4 +/- 2.6 kPa, and the oxygen availability fell from 1346 +/- 222 to 1039 +/- 239 ml/min, due to the additive effect of an increase in QS/QT from 10 +/- 4 to 21 +/- 5% and a fall in QT, from 7.7 +/- 1.2 to 5.5 +/- 1.1 1/min. With increasing levels of PEEP, despite a fall in P(A-a)O2, there was a reduction in oxygen availability. This was due to simultaneous reduction in QS/QT and QT. At a PEEP of 15cmH2O, the P(A-a)O2 was 21.2 +/- 7.1 kPa, oxygen availability 862 +/- 170 ml/min, QS/QT 13 +/- 4 and QT 4.4 +/- 0.6 1. It is concluded that PEEP ventilation significantly reduces QS/QT in extremely obese patients during anaesthesia and should be used in these patients if there is arterial hypoxemia despite a high FIO2.

Adult↗

A slide-rule for assessment of venous admixture.

Determination of venous admixture (physiological shunt, Qva/Qt) requires analysis of both arterial and mixed venous blood. When a pulmonary arterial catheter is not in use, the pulmonary oxygenating capacity may be assessed from arterial blood gas data, the fraction of inspired oxygen (FIO2) and an assumed value of the arterial-mixed venous oxygen content difference. To facilitate this process, a slide-rule based on the "virtual shunt" concept is presented. It permits rapid assessment of Qva/Qt from known values of arterial oxygen tension (PaO2) or saturation (SaO2) and FIO2 and may promote the choice of appropriate FIO2. The limitations of the slide-rule were studied theoretically and its validity was tested by comparing 100 determinations of virtual shunt with the corresponding Qva/Qt values. The slide-rule was found to estimate Qva/Qt more accurately than commonly used oxygenation indices such as the PaO2/FIO2 ratio.

Carbon Dioxide↗

Chemical incompatibility between procainamide hydrochloride and glucose following intravenous admixture.

The chemical reaction between procainamide hydrochloride and glucose following admixture to glucose infusion has been investigated. Substantial amounts (10-15% after 10 h at room temperature) of the procainamide is lost with the formation of a mixture of the corresponding alpha- and beta-glucosylamines. The chemical identity of the latter compounds was confirmed by 13C and 1H nuclear magnetic resonance spectroscopy.

Chromatography, High Pressure Liquid↗

Admixture Mapping Reveals Evidence for Multiple Mitonuclear Incompatibilities in Swordtail Fish Hybrids.

How barriers to gene flow arise between closely related species is one of the oldest questions in evolutionary biology. Classic models in evolutionary biology predict that negative epistatic interactions between variants in the genomes of diverged lineages, known as hybrid incompatibilities, will reduce viability or fertility in hybrids. The genetic architecture of these interactions and the evolutionary paths through which they arise have profound implications for the efficacy of hybrid incompatibilities as barriers to gene flow between species. While these questions have been studied using theoretical approaches for several decades, only recently has it become possible to genetically map larger numbers of hybrid incompatibilities. Here, we use admixture mapping in natural hybrid populations of swordtail fish (Xiphophorus) to identify hybrid incompatibilities involving genetic interactions between the mitochondrial and nuclear genomes. We find that at least nine regions of the genome are involved in mitonuclear incompatibilities. These incompatibilities involve interactions between the nuclear genome and the X. malinche mitochondria, the X. birchmanni mitochondria, or both. Moreover, they vary in the strength of selection they experience and the degree to which they limit gene flow in natural hybrid populations. Our results build a deeper understanding of the complex architecture of selection against incompatibilities in naturally hybridising species and highlight an important role of mitonuclear interactions in the evolution of reproductive barriers between closely related species.

Animals↗

Experimental posterior penetrating eye injury in the rhesus monkey: vitreous-lens admixture.

A standardised experimental posterior penetrating eye injury in the rhesus monkey with the vitreous-lens admixture resulted in limited fibrous ingrowth from the wound and minimal traction on the peripheral retina. Microscopically inflammation was noted in the iris, ciliary body, and as a perivascular infiltrate of the inner retina. Periretinal membranes did not occur, and cellular proliferation within the vitreous was less marked than observed after an identical wound and simulated vitreous haemorrhage in previously reported studies. The lens may be a less important stimulus to intravitreal fibroblastic proliferation than previously assumed.

Animals↗

Error due to dead-space admixture in single-breath method for estimation of pulmonary blood flow.

The single-breath method of Kim et al. (J. Appl. Physiol. 21: 1338-1344, 1966) for the estimation of pulmonary blood flow is based on a single-alveolus lung model for which an analytical relationship has been established between the kinetic behavior of the alveolar O2 and CO2 tensions and the pulmonary blood flow. The analysis is based on the assumption that the dead-space contribution to the expirate is negligible after expiration of a predefined volume. We have examined the influence of this assumption on the estimation of pulmonary blood flow by computer simulation in a lung model that incorporates deadspace contribution to the expirate. Data on the fractional contribution of the dead space to the expired gas were obtained from Tsunoda et al.'s study (J. Appl. Physiol. 32: 644-649, 1972) on the emptying pattern of normal adult lungs. The results show that failure to take account of the dead-space contribution can cause an underestimation in the pulmonary blood flow of greater than 30%. The error can be reduced by ignoring the first part of the expiration but only at the cost of an increase in the sensitivity of the single-breath method to measurement noise. This property of the system is demonstrated experimentally. The error due to dead-space admixture depends on the total volume of dead-space gas, the measurement noise, the pulmonary blood flow, and the emptying characteristics of the dead-space compartment during expiration. In normal subjects it is possible to optimize the experimental design so that the systematic error is less than 5% and the coefficient of variation is less than 10%.(ABSTRACT TRUNCATED AT 250 WORDS)

Computers↗

Transferrin variants as markers of migrations and admixture between populations in the Baltic Sea region.

Transferrin (TF) types were examined by isoelectric focusing in an attempt to elucidate migrations and admixture between populations in the Baltic Sea region. A highly significant heterogeneity between populations was found with respect to TF*C subtypes as well as the rare TF variants B2, B0-1 and DCHI. With the exception for Estonia, increased frequencies of the TF*C3 allele were observed east of the Baltic Sea. The island of Gotland in the middle of the Baltic Sea also showed a high TF*C3 frequency indicating an eastern influence. The TF*DCHI allele, a marker of eastern (Finno-Ugric) influence, was found in Finland and Estonia and on the island of Gotland, but not in mainland Sweden and in the Baltic peoples (Latvians and Lithuanians). These results indicate the presence of a Finno-Ugric, most likely Estonian or Livonian, genetic influence in the Gotland population.

Alleles↗

The LWb blood group as a marker of prehistoric Baltic migrations and admixture.

Archaeological findings and historical records indicate frequent migrations and exchange of genetic material between populations in the Baltic Sea area. However, there have so far been very few attempts to trace migrations in this area using genetic markers. We have studied the Baltic populations with respect to exceptional variations in the frequencies of the Landsteiner-Wiener (LW) blood group. The frequency of the uncommon LWb gene was high in the Balts, around 6% among Latvians and Lithuanians, very low among the other western Europeans (0-0.1%) and apparently absent in Asiatic and African populations. From the Baltic region of peak frequency there was a regular decline of LWb incidence (a descending cline) in the neighboring populations: 4.0% in the Estonians, 2.9% in the Finns, 2. 2% in the Vologda Russians, and 2.0% in the Poles. Thus the distribution of LWb suggests considerable and extensive Baltic admixture, especially in the north and northeast direction. In Southern Sweden with an LWb frequency of 0.3%, the Baltic influence appeared slight, while in the population of the Swedish island Gotland in the middle of the Baltic Sea there was a significantly increased LWb frequency of 1.0% compared with that of Western European countries. The distinction of codominantly inherited LW antigenic forms, LWa and LWb (previously Nea), is known to be due to a single base substitution. Based on our population data, it is plausible that the expansion of this point mutation occurred only once during human history. Furthermore, our data indicate that the expansion of the LWb mutation occurred in Balts and that LWb can be considered a 'Baltic tribal marker', its presence in other populations being an indicator of the degree of Baltic genetic influence.

Alleles↗

HLODs, trait models, and ascertainment: implications of admixture for parameter estimation and linkage detection.

Maximizing the homogeneity lod is known to be an appropriate procedure for estimating parameters of the trait model in an approximately 'ascertainment assumption free' (AAF) manner. We have investigated whether this same property also holds for the heterogeneity lod (HLOD). We show that, when the genetic models at linked and unlinked loci differ, HLODs are not AAF, and maximizing the HLOD yields parameter estimates that are for all practical purposes meaningless; indeed, the admixture parameter alpha does not even measure the proportion of linked families within the sample, as is commonly supposed. In spite of this, our results confirm a large body of evidence supporting the use of HLODs as robust tools for linkage detection, and suggest further that maximizing the HLOD over both alpha and parameters of the trait model can improve accuracy in estimation of the recombination fraction theta;. These findings have important implications for the optimal handling of nuisance parameters in linkage analysis, particularly when evaluating the evidence for or against linkage based on multiple independent heterogeneous sets of data.

Animals↗

Evidence for mtDNA admixture between the Finns and the Saami.

OBJECTIVES: The Finns, and to a more extreme extent the Saami, are genetic outliers in Europe. Despite the close geographical contact between these populations, no major contribution of Saami mtDNA haplotypes to the Finnish population has been detected. METHODS: To examine the extent of maternal gene flow from the Saami into Finnish populations, we determined the mtDNA variation in 403 persons living in four provinces in central and northern Finland. For all of these samples, we assessed the frequencies of mtDNA haplogroups and examined sequence variation in the hypervariable segment I (HVS-I). The resulting data were compared with published information for Saami populations. RESULTS: The frequencies of the mtDNA haplogroups differed between the populations of the four provinces, suggesting a distinction between northern and central Finland. Analysis of molecular variance suggested that the Saami deviated less from the population of northern Finland than from that of central Finland. Five HVS-I haplotypes, including that harboring the Saami motif and the Asian-specific haplogroup Z, were shared between the Finns and the Saami and allowed comparisons between the populations. Their frequency was highest in the Saami and decreased towards central Finland. CONCLUSIONS: The high frequency of certain mtDNA haplotypes considered to be Saami specific in the Finnish population suggests a genetic admixture, which appears to be more pronounced in northern Finland. Furthermore, the presence of haplogroup Z in the Finns and the Saami indicates that traces of Asian mtDNA genotypes have survived in the contemporary populations.

Adolescent↗

Relationship between African admixture and blood pressure variation in the Caribbean.

The genetic contribution to blood pressure variance is examined by studying a selected group of genes. Of 368 individuals, 48.1% received one-half or more of their genes from an African ancestor and of this group 18.1 and 17.0% exhibit systolic and diastolic hypertension, respectively. A chi-square test was used to examine the dependence of blood pressure on percentage African ancestry. The chi-square values were not significant for systolic or diastolic pressures. It is likely that other factors are strongly related to African admixture and these factors are the true modifiers of blood pressure.

Adolescent↗

Influence of peripheral blood admixture on the number of hematopoietic progenitor cells (CFU-GM and BFU-E) in human bone marrow aspirates.

Peripheral blood contamination in human bone marrow aspirates was calculated from the ratios between the erythrocyte and nucleated cell counts in both the bone marrow aspirate and a simultaneously obtained peripheral blood sample. This method is based upon experimental data which showed that the erythrocytes in bone marrow aspirates are mainly derived from the intravascular blood compartment. A strong negative correlation was found between the peripheral nucleated cell fraction (FBl) and the number of myeloid progenitor cells in 65 bone marrow samples (correlation coefficient r = -0.51; p less than 0.001). A similar correlation was found between erythroid progenitor cells and peripheral blood fraction (r = -0.55; p less than 0.01). The culture conditions were continuously monitored, using large batches of frozen marrow samples as controls. The correction for peripheral blood admixture permits a more reliable and reproducible interpretation of the quantitative results obtained from studies on the number of clonogenic cells in human bone marrow aspirates. Moreover, the method allows the interpretation of data obtained from bone marrow samples which are heavily contaminated by peripheral blood.

Biopsy, Needle↗

Effect of hydralazine on cardiac output and venous admixture in experimental lung injury.

The mechanism by which hydralazine increases venous admixture (QVA/QT) in the setting of lung injury was investigated in a canine model of noncardiogenic pulmonary edema. Permeability pulmonary edema was produced by administration of oleic acid, 0.08 ml/kg given intravenously to 9 mongrel dogs. After stabilization of lung injury, hydralazine was administered intravenously in a loading dose of 1 mg/kg and followed by a constant infusion at 0.05 mg/kg/h. To control for the effect of increased cardiac output (QT) on QVA/QT, a balloon catheter was placed in the inferior vena cava, and stepwise inflation of the balloon was used to impede venous return and maintain QT at predrug levels. Prior to inflation of the balloon catheter, administration of hydralazine produced a 51% decrease in total systemic resistance (TSR) and a 23% decrease in mean arterial pressure (Pa). In contrast, pulmonary vascular resistance (PVR) showed no significant change, and mean pulmonary artery pressure (Ppa) increased 47%. Cardiac output increased from 3.4 +/- 0.3 to 5.5 +/- 0.4 L/min (mean +/- SEM; p less than 0.01) after administration of hydralazine, and QVA/QT increased from 23 +/- 7 to 35 +/- 5% (p less than 0.05). Mean arterial oxygen tension (PaO2) showed no significant change. Inflation of the balloon in the inferior vena cava after hydralazine administration reduced QT to 3.1 +/- 0.4 L/min and QVA/QT to 28 +/- 4%. Neither of these values differed significantly from the prehydralazine levels. Similarly, values for Ppa and PVR after hydralazine administration plus balloon inflation did not differ significantly from predrug levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A simple method for rapid estimate of pulmonary venous admixture.

Data from 2,298 measurements of pulmonary venous admixture (QS/QT) performed in 733 patients were analyzed and processed in order to develop a method for rapid and reliable estimation of QS/QT by a simplified approach. Formulae and charts were obtained, which are easily suitable for use in all settings, and permit estimation of QS/QT with an 85%-93% control of its variability (r2 = 0.85-0.93, p less than 0.0001) simply on the basis of the measured arterial and central venous O2 tensions or saturations.

Adolescent↗

Total nutrient admixtures: theory and practice.

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

Chemistry, Pharmaceutical↗

Microbiological quality control study of "all-in-one" total parenteral nutrition admixtures.

A microbiological quality control study of parenteral nutrition (PN) is presented. The study was carried out in the Pharmacy and Microbiology Services of the Hospital de la Santa Creu i Sant Pau (Barcelona, Spain) from April 1991 to May 1998 and represents more than 25,000 lipid-containing PN admixtures prepared during that 7-year period. A randomized sampling procedure according to the cumulative sum control charts was performed and a 0.45-microm membrane filtration method was used as the microbiological test. Validation showed that the method is sensitive for sterility tests. Bacterial growth was observed on 59 filters (4.58% of the samples). A second control was made for these positive outcomes, and bacterial growth was found in only two cases. The patients' clinical history was reviewed and no relation between the microorganisms of the nutrition and the results obtained from blood cultures was observed. The quality control study revealed a low incidence of contamination in our PN preparation process.

Bacteria↗