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The genetic structure of admixed populations.

A method for simultaneously estimating the admixture proportions of a hybrid population and Wright's fixation index, FST, for that hybrid is presented. It is shown that the variance of admixture estimates can be partitioned into two components: (1) due to sample size, and (2) due to evolutionary variance (i.e., genetic drift). A chi-square test used to detect heterogeneity of admixture estimates from different alleles, or loci, can now be corrected for both sources of random errors. Hence, its value for the detection of natural selection from heterogeneous admixture estimates is improved. The estimation and testing procedures described above are independent of the dynamics of the admixture process. However, when the admixture dynamics can be specified, FST can be predicted from genetic principles. Two admixture models are considered here, gene flow and intermixture. These models are of value because they lead to very different predictions regarding the accumulation of genes from the parental populations and the accumulation of variance due to genetic drift. When there is not evidence for natural selection, and it is appropriate to apply these models to data, the variance effective size (Ne) of the hybrid population can be estimated. Applications are made to three human populations: two of these are Afro-American populations and one is a Yanomamö Indian village. Natural selection could not be detected using the chi-square test in any of these populations. However, estimates of effective population sizes do lead to a richer description of the genetic structure of these populations.

Black People↗

Chemical compatibility of inotropic and vasoactive agents delivered via a multiple line infusion system.

OBJECTIVES: To determine the chemical compatibility of three different triple drug admixtures diluted with either 5% dextrose in water or 0.9% NaCl solution when administered via a multiple line infusion system (Omni-Flow 4000, Abbott Laboratories, Abbott Park, IL). The triple drug admixtures were: a) dobutamine, dopamine, and norepinephrine; b) nitroglycerin, sodium nitroprusside, and dobutamine; and c) nitroglycerin, dopamine, and dobutamine. DESIGN: Two phase in vitro compatibility study. SETTING: Pharmaceutical laboratory. SUBJECTS: None. INTERVENTIONS: Phase I assessed chemical stability when the triple drug admixture was placed in a single container. In phase II, individual drug components of the admixtures were infused via the multiple line infusion system. Samples were collected at time 0, 1 hr, 2 hrs, 4 hrs, 12 hrs, and 24 hrs. All samples were frozen and stored at -70 degrees C until assayed. MEASUREMENTS AND MAIN RESULTS: Samples were assayed using stability-indicating high performance liquid chromatography. The triple drug admixtures were considered to be chemically stable if there was < or = 10% loss of stated potency over 24 hrs. In phase I, chemical stability was observed for all triple drug admixtures at 24 hrs. In phase II, dobutamine, dopamine, norepinephrine, and sodium nitroprusside showed chemical stability at 24 hrs. Nitroglycerin showed a two-fold increase in concentration at 24 hrs compared with the initial concentration through the test infusion system; however, this amount was still one third lower than originally anticipated. CONCLUSIONS: All triple drug admixtures were chemically stable when placed in single containers. Dobutamine, norepinephrine, and sodium nitroprusside showed chemical stability when delivered via a multiple line infusion system. The reduced recovery of nitroglycerin from the test infusion system may result from adsorption of the nitroglycerin to the polyvinyl chloride plastic cassette and tubing during infusion.

Chromatography, High Pressure Liquid↗

Variability of indices of hypoxemia in adult respiratory distress syndrome.

OBJECTIVE: To determine the usefulness of indices of hypoxemia in assessing patients with the adult respiratory distress syndrome (ARDS). DESIGN: Retrospective analysis of previously published data that describe the distributions of ventilation and pulmonary blood flow in ARDS. SETTING: University research laboratory. PATIENTS: Sixteen patients with ARDS. INTERVENTIONS: The FIO2 was varied between 0.21 and 1.0 in a computer model of gas exchange, based on a 50-compartment model of ventilation/perfusion inhomogeneity plus true shunt and deadspace. The indices of hypoxemia that were calculated as a function of inspired oxygen concentration included PaO2/FIO2, arterial/alveolar ratio (PaO2/alveolar PO2), the alveolar-arterial PO2 difference (P[A-a]O2), respiratory index (P[A-a]O2/PaO2), and venous admixture. MEASUREMENTS AND MAIN RESULTS: The PaO2/FIO2 ratio in patients with moderate shunts (< 30%) varied considerably with alteration in FIO2. At both extremes of FIO2, the PaO2/FIO2 in these patients was substantially greater than at intermediate FIO2. Patients with larger shunts (> 30%) had greater PaO2/FIO2 ratios at low FIO2, but the PaO2/FIO2 ratios decreased to relatively stable values at FIO2 values of > 0.5. In all patients, PaO2/FIO2 remained relatively stable at FIO2 values of > or = 0.5 and PaO2 values of < or = 100 torr (< or = 13.3 kPa). Other PO2-based indices exhibited less stability as FIO2 was varied. If hypoxemia resulted from true shunting, venous admixture was found to be stable at all FIO2 values. However, approximately one half of patients had clinically important hypoxemia resulting from mismatching of ventilation and blood flow. In these patients, venous admixture varied substantially with change in FIO2, and the degree of variation was proportional to the fraction of cardiac output perfusing gas exchange units with ventilation/perfusion ratios of < 0.1. CONCLUSIONS: All indices of hypoxemia are affected by changes in FIO2 in patients with ARDS. PaO2/FIO2 ratio exhibits the most stability at FIO2 values of > or = 0.5 and PaO2 values of < or = 100 torr (< or = 13.3 kPa), and is a useful estimation of the degree of gas exchange abnormality under usual clinical conditions. Venous admixture varies substantially with alteration of FIO2 in patients who have clinically important ventilation/perfusion abnormalities. Under these circumstances, venous admixture is a poor indicator of the efficiency of pulmonary oxygen exchange, even if venous admixture is calculated from measured arterial and venous oxygen content values. Estimated venous admixture, based on an assumed arterial-venous oxygen content difference, is even more unreliable.

Computer Simulation↗

Improvement of arterial oxygenation by selective infusion of prostaglandin E1 to ventilated lung during one-lung ventilation.

BACKGROUND: One-lung anesthesia provides a better surgical field for thoracic procedures but also impairs the arterial oxygenation and venous admixture. During one-lung ventilation, pulmonary vasoconstriction is assumed to be present within both ventilated and collapsed lungs. We propose that arterial oxygenation could be optimized by offsetting the vasoconstriction within the microcirculation of ventilated lung. METHOD: In an anesthetized dog model, incremental doses of prostaglandin E1 (PGE1) were selectively infused into the main trunk of the pulmonary artery of the ventilated lung after one-lung ventilation for 60 min (PGE1 group, n = 9). Arterial oxygenation and calculated venous admixture (Qs/Qt) was also assessed in a time-course control group (Control group, n = 5). During two-lung ventilation (FIO2: 0.66), arterial PO2 and venous admixture was 44.2 +/- 3.5 kPa and 10.7 +/- 2.3%, respectively. One-lung ventilation (FIO2: 0.66) with left lung collapsed reduced arterial PO2 to 11.6 +/- 1.7 kPa and increased venous admixture to 40.7 +/- 5.8% (P<0.001). Venous O2 tension also decreased from 6.3 +/- 0.7 kPa to 5.0 +/- 0.6 kPa with a slight increase in mean pulmonary artery pressure and pulmonary vascular resistance (P<0.05). RESULTS: During selective infusion of PGE1 at a dose of 0.04 to 0.2 mu g kg-1 min-1, there was a dose-dependent improvement in arterial PO2 with a parallel reduction of venous admixture during one-lung ventilation. Arterial PO2 increased to a maximum of 23.0 +/- 4.3 kPa, and the venous admixture decreased significantly to a minimum of 27.4 +/- 4.2% by PGE1 at a dose of 0.04-0.4 mu g kg-1 min-1 (P<0.01). PGE1 resulted in a small increase in cardiac output and decreases of pulmonary pressure and pulmonary vascular resistance at a relatively high dose of 0.4 mu g kg-1 min-1 during selective infusion (P<0.05). CONCLUSIONS: These results suggest that a selective pulmonary artery infusion of PGE1 to the ventilated lung within the dose range of 0.04-0.4 mu g kg-1 min-1 is practical and effective to improve arterial oxygenation and reduce venous admixture during one-lung ventilation.

Alprostadil↗

Compatibility and stability of linezolid injection admixed with three cephalosporin antibiotics.

OBJECTIVE: To evaluate the physical compatibility and chemical stability of linezolid (Zyvox-Pharmacia) 200 mg/100 mL admixed with cefazolin sodium 1 gram, ceftazidime 2 grams, and ceftriaxone sodium 1 gram for 7 days at 4 degrees C and 23 degrees C. DESIGN: Controlled experimental trial. SETTING: Laboratory. INTERVENTIONS: The test samples were prepared by adding the required amount of the cephalosporin antibiotic to bags of linezolid injection 200 mg/100 mL. MAIN OUTCOME MEASURES: Physical stability and chemical stability based on drug concentrations initially and after 1, 3, 5, and 7 days of storage at 4 degrees C and 23 degrees C protected from light. RESULTS: All of the linezolid admixtures with cephalosporins were clear when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low and exhibited little change. The cefazolin sodium-containing samples were colorless throughout the study. The admixtures with ceftazidime and ceftriaxone sodium had a slight yellow tinge initially, and the room temperature samples became a frank yellow color after 5 days. The refrigerated samples did not change color. High-performance liquid chromatography analysis found little or no loss of linezolid in any sample stored at either temperature throughout the study. Cefazolin sodium and ceftazidime in the linezolid admixtures at 4 degrees C remained stable for 7 days, but at 23 degrees C cefazolin sodium was stable for 3 days and ceftazidime for only 24 hours before cephalosporin decomposition exceeded 10%. Ceftriaxone sodium was less stable in the admixtures; 10% loss occurred in 3 days at 4 degrees C and more than 20% loss occurred in 24 hours at 23 degrees C. CONCLUSION: Admixtures of linezolid 200 mg/100 mL with cefazolin sodium 1 gram and ceftazidime 2 grams were physically compatible and chemically stable for at least 7 days stored at 4 degrees C protected from light and for 3 days and 1 day, respectively, at 23 degrees C protected from light. Admixtures of linezolid with ceftriaxone sodium 1 gram exhibited a rapid rate of cephalosporin loss at 23 degrees C, which precludes admixture of the two drugs.

Acetamides↗

Stability of pentamidine isethionate in 5% dextrose and 0.9% sodium chloride injections.

The stability of pentamidine isethionate in small-volume intravenous admixtures was studied. In an initial experiment, duplicate admixtures containing pentamidine 1 or 2 mg/mL were prepared using 100 mL each of 5% dextrose injection and 0.9% sodium chloride injection in polyvinyl chloride (PVC) bags. All solutions were kept at room temperature and were assayed at various times up to 48 hours by high-performance liquid chromatography. Solutions were also examined visually and tested for pH at each assay time. In a second experiment, single admixtures containing pentamidine 2 mg/mL were prepared in 100-mL PVC bags of both 5% dextrose injection and 0.9% sodium chloride injection. After time-zero determinations of pentamidine concentration, pH, and visual clarity, solutions were allowed to run through PVC infusion sets at 20 mL/hr. Samples were collected at the distal end of each set at various times up to five hours for analysis of pentamidine concentration, pH, and clarity. All admixtures in the initial experiment retained greater than 90% of initial concentration for the 48-hour study period. However, 5% dextrose admixtures infused through PVC administration sets showed a loss in initial concentration of about 2%, while 0.9% sodium chloride admixtures lost about 10% of initial concentration after infusion through these sets. The pH of all solutions in both experiments varied by less than 0.5 units, and no particulate matter or color change was noted in any of the admixtures. In the concentrations and diluents studied, pentamidine appears to be stable for 48 hours in PVC bags. Slight losses in the initial concentrations of these solutions after infusing them through PVC infusion sets may be caused by adsorption to the set.

Amidines↗

Stability of ganciclovir sodium and amino acids in parenteral nutrient solutions.

The stability of ganciclovir sodium and amino acids in parenteral nutrient solutions was studied. Three admixtures of ganciclovir sodium plus parenteral nutrient solution were prepared, one containing ganciclovir sodium 0.83 mg/mL, 1% amino acids, and 10% dextrose injection; one containing ganciclovir sodium 1.4 mg/mL, 2.5% amino acids, and 10% dextrose injection; and one containing ganciclovir sodium 1.4 mg/mL, 5% amino acids, and 25% dextrose injection. The solutions were visually inspected for precipitates, color change, and gas formation and were tested for pH. High-performance liquid chromatography was used to measure the concentration of ganciclovir and 16 amino acids in each admixture immediately and one, two, and three hours after preparation. There was no evidence of visual incompatibility in any of the admixtures, and pH did not vary appreciably during the study. The mean ganciclovir sodium concentration remaining was greater than 100% of the initial concentration for all the admixtures at one, two, and three hours. The mean amino acid concentration remaining in the admixtures with 2.5% or 5.0% amino acids was greater than 90% of the initial concentration for each amino acid at one, two, and three hours. The mean amino acid concentration remaining in the admixture with 1% amino acids was greater than 90% of the initial level at one and two hours. Ganciclovir sodium 0.83 mg/mL was stable for at least three hours in parenteral nutrient solution with 1% amino acids, and ganciclovir sodium 1.4 mg/mL was stable for at least three hours in admixtures with 2.5% or 5% amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Framework for identifying quantitative trait loci in association studies using structural equation modeling.

In this article, we suggest a framework for identifying quantitative trait loci (QTL) in association studies using structural equation modeling. Two tests to detect QTLs and estimate the proportion of variance they explain are discussed. The first test assumes that there is no population admixture and only requires that the subjects are genotyped. The second one is a TDT-like test that cannot give false-positive results due to population admixture but requires that the parents of the subjects are genotyped as well and that subjects have at least one heterozygous parent. Power calculations showed that with the first test, 100 subjects were generally sufficient to detect a locus that explained 10% and less than 1,000 subject to detect a locus that explained 1% of the total variance. To obtain the same power, the TDT-like test required an initial sample that was on average 1.7 times larger. Calculations showed that the first test was quite robust against population admixture and that the power of tests to detect admixture was good. This suggested that in the extreme and very specific conditions in which population admixture may cause false-positive findings, admixture can often be detected.

Alleles↗

Argentine population genetic structure: large variance in Amerindian contribution.

Argentine population genetic structure was examined using a set of 78 ancestry informative markers (AIMs) to assess the contributions of European, Amerindian, and African ancestry in 94 individuals members of this population. Using the Bayesian clustering algorithm STRUCTURE, the mean European contribution was 78%, the Amerindian contribution was 19.4%, and the African contribution was 2.5%. Similar results were found using weighted least mean square method: European, 80.2%; Amerindian, 18.1%; and African, 1.7%. Consistent with previous studies the current results showed very few individuals (four of 94) with greater than 10% African admixture. Notably, when individual admixture was examined, the Amerindian and European admixture showed a very large variance and individual Amerindian contribution ranged from 1.5 to 84.5% in the 94 individual Argentine subjects. These results indicate that admixture must be considered when clinical epidemiology or case control genetic analyses are studied in this population. Moreover, the current study provides a set of informative SNPs that can be used to ascertain or control for this potentially hidden stratification. In addition, the large variance in admixture proportions in individual Argentine subjects shown by this study suggests that this population is appropriate for future admixture mapping studies.

Asian People↗

Factors affecting the stability of nutritional emulsion mixtures.

The stability of oil droplets in complex nutritional admixtures is known to be affected by the presence of amino acids, dextrose and electrolytes. Hospital Pharmacists unable to meet demands for TPN admixtures sometimes turn to specialised commercial units but the supply of lipid admixtures by any facility remote from the user raises further challenges to admixture stability from various sources through exposure to temperature variations, transit effects etc. A number of interesting variances have been found in lipid admixtures arising from factors not previously recognised as significant. The batch of emulsion, container type and conditions of storage prior to use have been demonstrated to affect a moderately stable admixture. Whilst requiring further investigation, such factors must be considered for all new regimens and particularly to ensure the robustness of mixtures provided through a Compounding Service for Hospital or Home patients.

Journal Article↗

The distribution of immunoglobin allotypes in two Tlaxcaltecan populations.

The distribution of Glm(f, z, a, and x), G3m(b0, b1, b3, b5, c3, c5, g, s, t and v), A2m(1 and 2) and Km(1) (formerly Inv(1)) allotypic determinants has been examined in specimens from the inhabitants of two transplanted Tlaxcaltecan villages (Cuanalan and Saltillo). The results indicate that Gmza;g Am1, Gmza;g Am2, Gmzax;g Am1, Gmza;bst Am1, Gmza;bst Am2, Gmf;b Am1, Gmza,b Am1, Gmza;b Am2 and Km1 are polymorphic or marginally polymorphic in both populations, while Gmza;bc3,5 Am2, Gmza;bs Am2, and Gmzax;g Am2 were detected only in Saltillo. Two related individuals from Saltillo have either a Gmf;g Am1 or Gmf;-Am1 haplotype while a third unrelated individual had either a Gmf;g Am1 or Gm-;g Am1 haplotype. The frequencies observed for "residents" of Cuanalan are similar to those for other Indian populations in Mexico. Estimation of Caucasian and African admixture within the two communities indicates significant heterogeneity among the inhabitants of Cuanalan, in that Tlaxcaltecan residents have no detectable African admixture and significantly less Caucasian admixture than recent immigrants, with Tlaxcaltecan-immigrant hybrids intermediate, while no significant variation was observed among the subdivisions of Saltillo. However, Saltillo has greater Caucasian and African admixture than Cuanalan. Admixture estimates based on Gm haplotypes appear to agree much better with known historical events than those generated by blood groups, indicating that Gm is a better estimator of admixture than blood groups under certain circumstances.

Black People↗

Linkage analysis of a complex disease through use of admixed populations.

Linkage disequilibrium arising from the recent admixture of genetically distinct populations can be potentially useful in mapping genes for complex diseases. McKeigue has proposed a method that conditions on parental admixture to detect linkage. We show that this method tests for linkage only under specific assumptions, such as equal admixture in the parental generation and admixture that occurs in a single generation. In practice, these assumptions are unlikely to hold for natural populations, resulting in an inflation of the type I error rate when testing for linkage by this method. In this article, we generalize McKeigue's approach of testing for linkage to allow two different admixture models: (1) intermixture admixture and (2) continuous gene flow. We calculate the sample size required for a genomewide search by this method under different disease models: multiplicative, additive, recessive, and dominant. Our results show that the sample size required to obtain 90% power to detect a putative mutant allele at a genomewide significance level of 5% can usually be achieved in practice if informative markers are available at a density of 2 cM.

Alleles↗

Effects of carrier solution on insulin bioavailability.

BACKGROUND: The aim of our study is to assess the influence of the base solution on the availability of biologic insulin expressed in the value of total insulin using the radioimmunoassay method and to monitor the influence of the base solution on the total insulin concentration over time. METHODS: Total insulin in a saline and in a total nutrient admixture was measured using the RIA method. In 15 experiments, the application of the saline by a perfusor (8 IU Actrapid HM, 100 IU/1 mL + 20 mL saline) was carried out at time intervals of baseline, 5, 10, 30, 60, 90, and 210 minutes. The application of the total nutrient admixture (8 IU Actrapid HM + 20 mL total nutrient admixture) was carried out in the same way. The MANOVA, ANOVA and paired t test with Bonferroni correction were then used for statistical evaluation. RESULTS: The average values of insulin concentration in saline at given time intervals were 21.5 +/- 11.3 mIU/L (5.4% of the theoretically calculated concentration). The level of insulin in the total nutrient admixture did not change over time, and it reached the values of 115.2 +/- 22.3 (28.8% of the theoretically calculated concentration). Changes in insulin concentration in time were found only in the saline (ANOVA time effect p < .001 for saline; p = .26 for total nutrient admixture). CONCLUSIONS: The availability of insulin was significantly higher in the total nutrient admixture solution than in the saline in the 3.5-hour experiment. The dependence of insulin concentration on time is present only in saline, and the main changes in insulin bioavailability are within first 60 minutes. The difference could be caused by smaller insulin absorption to the syringe walls and to the set, owing to the amino acids in the mixture. The question whether the amino acid concentration affects insulin bioavailability stays opened to other studies.

Analysis of Variance↗

Compatibility and stability of paclitaxel combined with cisplatin and with carboplatin in infusion solutions.

OBJECTIVE: To evaluate the physical compatibility and chemical stability of paclitaxel at concentrations of 0.3 and 1.2 mg/mL with cisplatin 0.2 mg/mL in NaCl 0.9% injection and with carboplatin 2 mg/mL in NaCl 0.9% injection and dextrose 5% injection over 7 days at 4, 23, and 32 degrees C. DESIGN: The test samples were prepared in polyolefin bags of the infusion solutions at the required drug concentrations. Evaluations were performed initially and after 4 hours, and 1, 3, 5, and 7 days of storage at temperatures of 4, 23, and 32 degrees C for physical and chemical stability. Physical stability was assessed by using visual observation in normal light and using a high-intensity monodirectional light beam. In addition, turbidity and particle content were measured electronically. Chemical stability of the three drugs was evaluated by using three stability-indicating HPLC analytical techniques. RESULTS: All samples were physically stable through 1 day. However, microcrystalline precipitation of paclitaxel occurred in 3 days in some samples and within 5 days in all samples. Paclitaxel concentrations remained above 90% in all samples throughout the study. Cisplatin admixtures exhibited paclitaxel concentration-dependent decomposition with cisplatin losses of approximately 5-8% in 4 hours and approximately 20% in 1 day at 23 and 32 degrees C in the paclitaxel 1.2 mg/mL admixtures. With paclitaxel 0.3 mg/mL in the admixtures, cisplatin losses were about 10% in 7 days at these temperatures. Carboplatin in admixtures with both concentrations of paclitaxel was stable for 7 days at 4 degrees C, but sustained losses of about 10% and 12% in 3 days at 23 and 32 degrees C, respectively. CONCLUSIONS: Admixtures of paclitaxel 0.3 and 1.2 mg/mL with cisplatin and carboplatin are limited in their utility time by both paclitaxel microcrystalline precipitation and decomposition of cisplatin and carboplatin. The admixture of paclitaxel 1.2 mg/mL with cisplatin 0.2 mg/mL in NaCl 0.9% injection exhibits unacceptable cisplatin loss in 24 hours. All other combinations were physically and chemically stable for at least 24 hours at 4, 23, and 32 degrees C.

Antineoplastic Agents↗

Compatibility of budesonide inhalation suspension with four nebulizing solutions.

BACKGROUND: Nebulizable medications often are mixed to simplify asthma medication regimens. OBJECTIVE: To establish the in vitro chemical compatibility and stability of budesonide inhalation suspension 0.25 mg/2 mL and 0.5 mg/2 mL mixed in Pari LC Plus jet nebulizer cups with 3 mL of levalbuterol hydrochloride 0.63 mg/3 mL and 1.25 mg/3 mL; 0.5 mL of albuterol sulfate 5 mg/mL; 2 mL of cromolyn sodium 20 mg/2 mL; or 2.5 mL of ipratropium bromide 0.2 mg/mL. METHODS: We developed and validated isocratic HPLC methods to permit separation of the admixture components from aliquots taken 0, 5, 15, and 30 minutes after mixing. Admixtures were prepared and analyzed at room temperature. Each assay was conducted 3 times using separate nebulizer cups. All components were quantified by external standards using HPLC-derived peak area. Appearance and pH of the admixtures were recorded. RESULTS: No additional peaks occurred in any HPLC chromatogram for any medication from any admixture. With the exception of ipratropium bromide at 93%, each admixture retained >97% of the initial concentration of each medication in the nebulizer cup. There was no significant change in pH or visual identification of a precipitate in any admixture of active drugs. CONCLUSIONS: These data support the chemical compatibility of budesonide inhalation suspension for up to 30 minutes with other commonly used nebulized medications for controlling pediatric asthma symptoms.

Anti-Asthmatic Agents↗

[Pulmonary gas exchange under room air respiration in hypercapneic patients].

INTRODUCTION: The alveolar-capillary oxygen difference, P(A-a)O2, is important in the study of gas exchange disorders, however does not give us reliable results when applied to hypercapneic patients. On the other hand the venous admixture calculation, seems to be able to diagnose alveolar-capillary gas exchange difficulty of any kind. OBJECTIVE: Checking the reliability of the alveolar-capillary oxygen difference to diagnose the alveolar-capillary disorder in face of alveolar hypoventilation, by using the venous admixture calculation as standard. METHODS: 83 blood gas analysis from patients with hypercapnia were submitted to venous admixture and P(A-a)O2 determination with the measured PaCO2 and a fixed PaCO2 of 40 mmHg. The results where compared by correlation test. RESULTS: The mean partial pressure of arterial oxygen and carbon dioxide were respectively, 50.8+/-10.4 and 51.7+/-6.4 mmHg; the mean value of P(A-a)O2, amended P(A-a)O2 and venous admixture were respectively 26.6+/-10.2 mmHg, 40.4+/-10.8 mmHg and 37+/-15.2%. The correlation coefficient between the venous admixture versus P(A-a)O2 was 0.61 p<0.00001 and the venous admixture versus "amended" P(A-a)O2 was 0.89 p<0.00001. CONCLUSION: The use of the oxygen alveolar-capillary gradient in chronically hypercapneic patient does not reach the diagnosis of alveolar-capillary gas exchange disorder which usually comes together with alveolar hypoventilation.

Adult↗

Compatibility of ciprofloxacin injection with selected drugs and solutions.

The compatibility of ciprofloxacin injection with selected antimicrobials and aminophylline was studied. Ciprofloxacin, amikacin sulfate, aminophylline, clindamycin phosphate, gentamicin sulfate, and tobramycin sulfate were mixed separately in minibags containing 0.9% sodium chloride injection or 5% dextrose injection; admixtures were stored for up to 48 hours at either 4 degrees C or 25 degrees C. Ciprofloxacin was also combined separately with each of the other drugs and solutions and stored under the same conditions. In addition, ciprofloxacin was combined with metronidazole in ready-to-use mini-bags of the latter drug and stored at 25 degrees C. Drug concentrations were measured by fluorescence polarization immunoassay or high-performance liquid chromatography. All admixtures were also examined visually. Stability was defined as retention of at least 90% of the original drug concentration with no visual evidence of incompatibility. With one exception, drugs in all single-drug admixtures were stable for 48 hours. The drug concentration eight hours after amikacin was mixed in 0.9% sodium chloride and refrigerated was 89% of the original concentration. When ciprofloxacin was combined with gentamicin, metronidazole, or tobramycin, all of the involved drugs were stable for 48 hours. Compatibility of ciprofloxacin-amikacin admixtures depended on the fluid and storage temperature; all such admixtures were stable for at least eight hours. A precipitate formed immediately whenever ciprofloxacin was mixed with clindamycin and within four hours after ciprofloxacin was mixed with aminophylline. Ciprofloxacin injection was compatible with gentamicin, metronidazole, and tobramycin and incompatible with aminophylline and clindamycin. The compatibility of ciprofloxacin-amikacin admixtures depended on the i.v. solution and storage temperature.

Amikacin↗

Stability of nizatidine in commonly used intravenous fluids and containers.

The stability of nizatidine in commonly used i.v. fluids stored in glass and plastic containers was studied. Stock solutions of nizatidine 0.75, 1.5, and 3.0 mg/mL in 15 i.v. fluids were prepared using nizatidine injection 25 mg/mL. Six 50-mL aliquots of each solution were transferred to separate glass infusion bottles and stored at room temperature or under refrigeration. Twenty-one 40-mL aliquots of additional stock solutions of nizatidine 0.75 and 3.0 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection were transferred to polyvinyl chloride (PVC) bags and stored at room or refrigerated temperature; some of these solutions were frozen, thawed, and refrigerated before analysis. Samples of each admixture were analyzed after 0.5, 1, 2, 3, and 7 days of storage for nizatidine concentration using a stability-indicating high-performance liquid chromatographic assay and also for visible changes and pH. The concentration of nizatidine in each admixture remained within 92%-106% of actual initial storage concentration throughout the study period, with the exception of nizatidine 3.0 mg/mL in 8.5% amino acid injection. The stability of nizatidine in admixtures stored in polyvinyl chloride bags was similar to that of admixtures stored in glass bottles. In the i.v. fluids, concentrations, and containers studied, nizatidine admixtures are stable for at least 7 days at either room or refrigerated temperature and 30 days when stored frozen in polyvinyl chloride bags. Admixtures of nizatidine 3.0 mg/mL in 8.5% amino acid injection should not be stored at room temperature for longer than four days.

Chromatography, High Pressure Liquid↗