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Stability of clindamycin phosphate with aztreonam, ceftazidime sodium, ceftriaxone sodium, or piperacillin sodium in two intravenous solutions.

In admixtures containing clindamycin and either aztreonam, ceftazidime, ceftriaxone, or piperacillin in either 5% dextrose injection (D5W) or 0.9% sodium chloride injection (NS), the stability of each drug was studied. Each of the following combinations of drugs was added to 100-mL glass bottles of base solution: clindamycin phosphate 0.9 g and aztreonam 2.0 g, clindamycin phosphate 0.9 g and ceftazidime sodium 2.0 g, clindamycin phosphate 1.2 g and ceftriaxone sodium 2.0 g, and clindamycin phosphate 0.9 g and piperacillin sodium 4.0 g. Duplicate samples were prepared. Admixtures containing each single drug were also tested. Samples were visually inspected and tested for pH and drug concentration immediately after mixing and at 1, 4, 8, 12, 24, and 48 hours of storage in room temperature and light. Drug concentrations were determined by high-performance liquid chromatographic assay methods. Ceftriaxone retained greater than 90% of its original concentration for 24 hours in single-drug admixtures in NS, for eight hours with clindamycin in NS, and for one hour with clindamycin in D5W. Ceftazidime retained greater than 90% potency for 24 hours with clindamycin in D5W. In all other test admixtures, all drugs were stable for 48 hours. Under the conditions studied, clindamycin is compatible in the admixtures tested with aztreonam and piperacillin. Admixtures of clindamycin and ceftazidime in D5W should be used within 24 hours at room temperature. Clindamycin and ceftriaxone can be mixed in NS if administered within eight hours, but ceftriaxone is stable for only one hour in combination with clindamycin in D5W.

Aztreonam↗

Stability of trimethoprim-sulfamethoxazole injection in two infusion fluids.

The concentrations over time of trimethoprim (TMP) and sulfamethoxazole (SMZ) in solution after preparations of admixtures of TMP-SMZ in 5% dextrose injection (D5W) and in 0.9% sodium chloride injection (NS) were measured. Admixtures (50 ml) containing three TMP concentrations (0.64 mg/ml, 1.6 mg/ml, and 3.2 mg/ml) and three SMZ concentrations (3.2 mg/ml, 8.0 mg/ml, and 16 mg/ml) were prepared in D5W or NS, representing 1:25 v/v, 1:10 v/v, and 1:5 v/v dilutions of TMP-SMZ injection, respectively. Aliquots of each admixture were obtained immediately upon dilution and after 0.5, 1, 2, 4, 8, and 24 hours. The aliquots were filtered and assayed for TMP and SMZ by high-pressure liquid chromatography. Each mixture was inspected visually for any changes in clarity or color, and the pH of each admixture was measured over time. The concentration of SMZ in all admixtures remained constant over 24-hour study period. The TMP concentration did not change significantly (less than 10% of initial concentration) after 1:25 v/v dilutions in either D5W or NS for up to four hours. With a dilution of 1:10 v/vv D5W TMP was stable at D5W for up to two hours. TMP precipitated rapidly in dilutions of 1:5 v/v in either D5W or NS. The pH of the admixtures ranged from 9.39 to 10.10. D5W is the preferred diluent for TMP-SMZ injection if a dilution ratio of 1:10 v/v is desired. Either D5W or NS may be used if a dilution ratio of 1:25 v/v is desired.

Drug Combinations↗

Stability of aztreonam and ampicillin sodium-sulbactam sodium in 0.9% sodium chloride injection.

The stability of aztreonam, ampicillin sodium, and sulbactam sodium admixed in 0.9% sodium chloride injection and stored at room temperature and under refrigeration was studied. Each of the following admixtures was prepared in 0.9% sodium chloride injection: (1) aztreonam 10 mg/mL; (2) ampicillin 20 mg/mL (as the sodium salt) and sulbactam 10 mg/mL (as the sodium salt); and (3) aztreonam 10 mg/mL, ampicillin 20 mg/mL, and sulbactam 10 mg/mL. Three minibags of each admixture were stored at room temperature and three were refrigerated. Every 12 hours, up to 96 hours, the admixtures were visually inspected and 5-mL samples were withdrawn for high-performance liquid chromatography and pH testing. No color change or precipitation was observed in any sample. In admixtures containing ampicillin, ampicillin was the first or only drug to lose more than 10% of initial concentration. In the ampicillin-sulbactam admixture, ampicillin was stable for 32 hours at room temperature and 68 hours refrigerated. In the aztreonam-ampicillin-sulbactam admixture, ampicillin was stable for 30 hours at room temperature and 94 hours refrigerated. Aztreonam 10 mg/mL, ampicillin 20 mg/mL (as the sodium salt), and sulbactam 10 mg/mL (as the sodium salt) in 0.9% sodium chloride injection were stable in combination for up to 30 hours at room temperature and 94 hours under refrigeration.

Ampicillin↗

An archaic reference-free method to jointly infer Neanderthal and Denisovan introgressed segments in modern human genomes.

Admixture between populations is a common feature of human history. Admixture events introduce new genetic variation that can fuel evolution. Characterizing the significance of admixture events on the evolution of populations across various species is of great interest to evolutionary geneticists. Local Ancestry Inference (LAI) methods infer genetic ancestry of an individual at a particular chromosomal location. Certain methods specialize in detecting archaic introgression, which consists of interbreeding between modern and archaic humans like Neanderthals and Denisovans. Most current LAI methods allow the detection of a single archaic ancestry, and post-processing may distinguish between multiple waves of introgression. These methods vary in how they choose archaic or modern reference genomes for the inference. Here, we present a new HMM-based method (DAIseg), which has the advantage of simultaneously distinguishing between multiple waves of ancient and recent admixture, using only modern human reference genomes. Simulations demonstrate that DAIseg achieves higher overall performance than state-of-the-art methods. We also apply DAIseg to Papuan populations to jointly detect Denisovan and Neanderthal introgressed segments, and identify a higher number of archaic segments than previous methods. Analysis of inferred introgressed segments, shows that we can identify evidence for two Denisovan introgression events in Papuans. Overall, on top of being able to deal with both Archaic and recent admixture, DAIseg provides a more principled approach for detecting and classifying Denisovan and Neanderthal segments which will improve downstream analysis of introgressed segments to infer the impact of archaic introgression in humans.

Denisovan↗

DYS19 and DYS199 loci in a Chilean population of mixed ancestry.

The current Chilean population originated from admixture between aboriginal populations (Amerindians) and Spanish conquerors of European origin. Consequently, the unions that gave rise to the Chilean population were chiefly between Spanish males and aboriginal females, and not the converse. To test the hypothesis that the Y chromosome of the Chilean population is mainly of Spanish origin, while the other chromosomes are from mixed (European and aboriginal) origin, we studied the DYS19 and DYS199 loci in two samples. One sample was obtained from a high socioeconomic stratum, while a second sample was from a low stratum. We studied male blood donors (N = 187) from Santiago, the capital of the country. Subjects were typed for the autosomal ABO and Rh (locus D) blood groups, and for the Y-linked DYS19 and the DYS199 loci, reported as Y-chromosome haplotypes. The aboriginal admixture was estimated for each genetic marker. The percentage of aboriginal admixture was 38.17% for the ABO system and 31.28% for the Rh system in the low socioeconomic stratum and 19.22% and 22.5%, respectively, in the high stratum. Y-chromosome haplotype frequencies constructed from the DYS19 and DYS199 loci demonstrated that the main haplotypes were DYS19*14/DYS199 C, as is often the case with many European populations, and DYS19*13/DYS199 C. The aboriginal admixture from Y-haplotype frequencies was estimated to be 15.83% in the low socioeconomic stratum and 6.91% in the high stratum. These values are lower than the values found using autosomal genetic markers, and are consistent with the historical background of the population studied. This study highlights the population genetic consequences of the asymmetric pattern of genome admixture between two ancestral populations (European and Amerindian).

Chile↗

Gene flow and variation in stature and craniofacial dimensions among indigenous populations of southern Mexico, Guatemala, and Honduras.

Populations with histories of outbreeding tend to be taller even in the face of seemingly unchanged health and nutritional circumstances, while inbreeding generally results in a negative correlation between body dimensions and level of inbreeding. Populations that have experienced a positive secular trend in stature and maturation typically have histories of higher outbreeding rates in combination with improved nutritional, health, and economic conditions, suggesting a genetic-environment interaction. In general, Middle American Indians have not experienced a secular trend in stature, nor a substantial increase in their standard of living, but they have experienced varying degrees of admixture with Spanish and African populations since the Spanish Conquest. The relationship between estimated gene flow and variation in several anthropometric dimensions is thus considered in indigenous Mesoamerican populations. Available data on height, sitting height, craniofacial dimensions, and admixture rate of Indian populations from southern Mexico, Guatemala, and Honduras were assembled from the literature. The population mean data on 3,371 adults from 23 populations for males and 18 for females were analyzed by regression with anthropometry as the dependent variable, and log10 of admixture as the independent variable. Admixture was less than or equal to 28.9% in this study and is suggestive of a primarily traditional Indian cultural and economic base. The results suggest that populations with higher admixture tend to be taller, and that the increase in stature is due to greater subischial length in both sexes. A decrease in nasion-menton height, and an increase in nasal breadth, nasal height, and the nasal index is suggested for the dimensions of the craniofacial complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Anthropometry↗

Elevated male European and female African contributions to the genomes of African American individuals.

The differential relative contribution of males and females from Africa and Europe to individual African American genomes is relevant to mapping genes utilizing admixture analysis. The assessment of ancestral population contributions to the four types of genomic DNA (autosomes, X and Y chromosomes, and mitochondrial) with their differing modes of inheritance is most easily addressed in males. A thorough evaluation of 93 African American males for 2,018 autosomal single nucleotide polymorphic (SNP) markers, 121 X chromosome SNPs, 10 Y chromosome haplogroups specified by SNPs, and six haplogroup defining mtDNA SNPs is presented. A distinct lack of correlation observed between the X chromosome and the autosomal admixture fractions supports separate treatment of these chromosomes in admixture-based gene mapping applications. The European genetic contributions were highest (and African lowest) for the Y chromosome (28.46%), followed by the autosomes (19.99%), then the X chromosome (12.11%), and the mtDNA (8.51%). The relative order of admixture fractions in the genomic compartments validates previous studies that suggested sex-biased gene flow with elevated European male and African female contributions. There is a threefold higher European male contribution compared with European females (Y chromosome vs. mtDNA) to the genomes of African American individuals meaning that admixture-based gene discovery will have the most power for the autosomes and will be more limited for X chromosome analysis.

Black or African American↗

From local hybrid functionals to "localized local hybrid" potentials: formalism and thermochemical tests.

Hybrid exchange-correlation functionals with position-dependent exact-exchange admixture (local hybrid functionals) have been implemented self-consistently for the first time. Functional derivatives with respect to the occupied orbitals have been derived and were subsequently transformed into local and multiplicative potentials within the framework of the optimized effective potential. The resulting local and multiplicative Kohn-Sham potentials are termed "localized local hybrid" (LLH) potentials. They have been evaluated in calculations of atomization energies for a series of main-group molecules. It is shown that LLH potentials yield somewhat better thermochemical results than non-self-consistent post-GGA calculations with the same local hybrid energy functionals for orbitals obtained with a different potential. The choice of the "local mixing function" (LMF) is discussed. This is the key quantity for the performance of local hybrid functionals that determines the amount of exact-exchange admixture at a given point in space. Careful analyses of average exact-exchange admixtures and of the spatial variation of two different LMFs for various molecules provide insight into the shortcomings of the currently used local hybrid functionals. Beyond a too large average exact-exchange admixture, both LMFs used appear to provide an unbalanced description of exact-exchange admixture across bonds to hydrogen. LLH potentials open the way for property calculations with local hybrid functionals.

Journal Article↗

Mechanisms of anti-tumor action of Corynebacterium parvum. II. Potentiated cytolytic T cell response and its tumor-induced suppression.

It was shown that subcutaneous implantation of P815 tumor cells admixed with Corynebacterium parvum resulted in the emergence of a tumor that grew for 9-10 d and then regressed. The onset of tumor aggression was preceded by the substantial generation in the draining lymph node and spleen of T cells capable of specifically lysing P815 target cells in vitro. The finding that the magnitude of this cytolytic response was much greater than the cytolytic response to a control tumor that grew progressively is consistent with the hypothesis that the anti-tumor action of C. parvum is based on its capacity to augment the production of T cells sensitized to tumor-specific transplantation antigens. This adjuvant action of C. parvum was revealed by additional experiments in which irradiated, nonreplicating tumor cells were substituted for living tumor cells in the admixture. The results support the conclusion that the potentiated cytolytic response to subcutaneous injection of an admixture of irradiated tumor cells and C. parvum is responsible for the ability of this admixture to cause the regression of a test tumor growing at a distant site. Finally, it was shown that the failure of the therapeutic admixture to cause the regression of distant test tumors above a certain size was associated with a failure of the admixture to cause a potentiated, anti-tumor cytolytic response. We discussed the possibility that this failure was caused by the presence of a tumor-induced state of immunosuppression.

Animals↗

Stability of amphotericin B in an extemporaneously prepared i.v. fat emulsion.

The stability of amphotericin B in an extemporaneously prepared i.v. fat emulsion was studied. Admixtures of amphotericin B 0.5, 1, and 2 mg/mL were prepared by adding 10, 20, and 40 mL of amphotericin B 5 mg/mL to 90, 80, and 60 mL, respectively, of 20% fat emulsion. The admixtures were stored in glass vacuum containers at 20-25 degrees C and exposed to fluorescent light, 20-25 degrees C and protected from light, or 4-8 degrees C and protected from light. A sample was withdrawn from each container at 0, 4, 12, and 24 hours and at 2, 4, 7, and 15 days for analysis of amphotericin B concentration by high-performance liquid chromatography and for visual evaluations; these samples were immediately frozen until analyzed. A sample was withdrawn from one container of amphotericin B 1 and 2 mg/mL for each storage condition at 0, 7, and 15 days for immediate determination of particle-size distribution with a fluorescinated-antibody cell sorter. Amphotericin B 0.5 mg/mL in 20% fat emulsion was stable for one week under all the storage conditions. Amphotericin B in the 1- and 2-mg/mL admixtures was stable for up to four days at 20-25 degrees C exposed to fluorescent light, and for up to one week at 20-25 degrees C protected from light and at 4-8 degrees C protected from light. There was no visible evidence of incompatibility. There were no substantial changes in particle-size distribution for the 1-mg/mL admixtures; appreciable changes were detected for the 2-mg/mL admixtures. Amphotericin B 1 and 2 mg/mL was stable in 20% fat emulsion for four days at 20-25 degrees C exposed to fluorescent light and for seven days at 20-25 degrees C protected from light or at 4-8 degrees C; amphotericin B 0.5 mg/mL was stable in 20% fat emulsion for seven days under the three storage conditions.

Amphotericin B↗

Largest-Scale Genomic Resource Reconstructing the Genetic Origin, Population Structure, and Biological Adaptations of the Hui People.

Historical and archaeological records indicate that the Maritime and Land Silk Roads played a pivotal role in facilitating Trans-Eurasian migrations and cultural exchanges. However, the extent to which population movements or the spread of ideas shape Chinese Hui populations remains debated. We present the largest genomic resource to date, including 2,280 Hui individuals sequenced or genotyped from 30 diverse regions, to examine the genetic origins, population structure, and biological adaptations of this underrepresented group in global human genome research. We identified a detailed population structure characterized by five distinct genetic lineages of the Hui, influenced by geography and varying gene flow. The admixture history and demographic events suggest that the northwestern and northern Hui lineages emerged from demic diffusion during the Tang and Yuan Dynasties via the Land Silk Road. In contrast, the southern and island Hui lineages reflect cultural diffusion along the Maritime Silk Road, while the mixed southern-northern lineage likely developed through a combination of demic and cultural diffusion. Our findings support a hybrid model for Hui formation, indicating that both demographic processes and sociocultural transmissions contributed to their population history. We identified east-west highly differentiated variants and pre- and post-admixture adaptations in Hui genomes, demonstrating that admixture-driven adaptive or neutral variants impacted susceptibility to cardiovascular diseases and immune- and diet-related traits. These adaptive signatures include post-admixture signals of SLC24A5 and ECHDC1 in the Hui, as well as pre-admixture signals of the HLA region, BCL2A1, and KCNH8 in the East Asian source. Overall, our study suggests that Han-related genetic components helped the Hui population rapidly adapt to new local environments. Additionally, the frequency spectrum of clinically essential variants differed significantly between Hui and Han individuals, emphasizing the importance of including underrepresented populations in genomic research to promote health equity.

Humans↗

Effects of pulmonary blood flow and mixed venous O2 tension on gas exchange in dogs.

The authors investigated whether the increases in venous admixture and intrapulmonary shunt which occur with increases in cardiac output (Qt) results from an effect mediated by mixed venous PO2 (PVO2) or an effect mediated by the increase in pulmonary blood flow. Using a veno-venous bypass system thay were able to alter PVO2 independent of variations in Qt and vice versa. During room air ventilation of dogs with normal lungs at constant Qt, an increase in PVO2 from 33 +/- 7 (mean +/- SD) to 54 +/- 9 mmHg (P less than 0.05) resulted in a decrease in venous admixture from 22 +/- 11 to 13 +/- 4% (P less than 0.05). During room air ventilation of normal dogs at a constant PVO2, raising Qt from 2.16 +/- .53 to 3.49 +/- 0.91 l/min (P less than 0.05) increased venous admixture from 10 +/- 5 to 16 +/- 5% (P less than 0.05). During oxygen ventilation in these two groups of dogs, changes in PVO2 and Qt had no effect on shunt. During oxygen ventilation of dogs with significant shunts from oleic-acid-induced pulmonary edema, independent increases in either PVO2 or pulmonary blood flow resulted in increased shunt. At constant Ot, an increase in PVO2 from 30 +/- 8 to 52 +/- 3 mmHg (P less than 0.05) resulted in an increase in shunt from 39 +/- 12 to 43 +/- 12% (P less than 0.05). When PVO2 remained constant, increasing Qt from 1.97 pm 0.42 to 3.61 +/- 0.50 l/min (P less than 0.05) resulted in an increase in shunt from 47 +/- 17 to 53 +/- 15% (P less than 0.05). The authors conclude that during oxygen ventilation, normal dogs have shunts which are unaffected by changes in blood flow or PVO2. Increases in pulmonary blood flow increase venous admixture during room air ventilation, while increases in PVO2 decrease venous admixture during air ventilation. In edematous lungs, increases in either PVO2 or pulmonary blood flow increase shunt.

Animals↗

Practical aspects of multichamber bags for total parenteral nutrition.

PURPOSE OF REVIEW: Ready-to-use all-in-one admixtures are standards for short and long-term parenteral nutrition. Their limited stability does not allow storage over prolonged periods of time. Multichamber bags represent industrially manufactured near complete standard parenteral nutrition premixes with extended shelf lives. This review focuses on the characterization of multichamber bags, their influence on parenteral nutrition practice, the need for individual parenteral nutrition compounding, and the role of the pharmacist in the nutrition team. RECENT FINDINGS: The all-in-one admixture concept, its correlation with parenteral nutrition effectiveness, safety, and pharmaceutical issues are reviewed. Multichamber bags, the bag material, their use and practical handling are addressed. SUMMARY: Newly developed container materials are mainly responsible for the increased stability of multichamber bag parenteral nutrition premixes. Multichamber bags are used for (standard) parenteral nutrition in adults. Multichamber bags cannot eliminate individualized all-in-one parenteral nutrition compounding. Pharmaceutical assistance with expertise in compatibility and stability is mandatory for the nutrition team to implement and control good parenteral nutrition practices, e.g. to convert multichamber bags into complete ready-to-use all-in-one admixtures or to compound individualized regimens. The incorporation of additional components into parenteral nutrition admixtures (pharmaconutrients, drugs) must rely on documented compatibility with the parenteral nutrition admixtures. Multichamber bags have their advantages and limitations. Studies on the effectiveness and costs of multichamber bags are needed to meet the expectations of pharmacists, physicians, nurses, and industry for optimal parenteral nutrition in patients.

Drug Compounding↗

The effects of nitric oxide inhalation on respiratory mechanics and gas exchange during endotoxaemia in the pig.

BACKGROUND: In the adult respiratory distress syndrome, nitric oxide (NO) inhalation improves oxygenation through reducing ventilation-perfusion mismatching, but detailed information on the pulmonary effects of NO inhalation in septic shock is scarce. The present study investigated the effects of inhaled NO on alveolar dead space (Vdalv) and venous admixture as well as on respiratory system compliance (Crs) and respiratory system resistance (Rrs) in a porcine model of septic shock. Protective effects of NO are discussed. METHODS: Thirteen anaesthetised and ventilated pigs were given an infusion of endotoxin for an observation time of 220 min to induce acute lung injury (ALI). In the NO-early group (n=6), an inhalation of 60 ppm NO was started simultaneously with the endotoxin infusion and continued for 190 min. In 7 control/NO-late animals, 60 ppm NO was administered for 30 min following 190 min of endotoxin infusion. Haemodynamics, single-breath CO2-, pressure-, and flow signals were recorded. RESULTS: Endotoxin induced haemoconcentration, pulmonary vasoconstriction, and a decrease in Crs, while venous admixture, Vdalv, and Rrs increased. In the NO-early group, the pulmonary vasoconstriction was attenuated, no increase in pulmonary venous admixture or in Vdalv was seen before cessation of NO, and the improvements in oxygenation outlasted the NO inhalation. In the control/NO-late group, the NO inhalation reversed the changes in dead space and venous admixture. NO had no effect on the changes in respiratory mechanics. CONCLUSION: In porcine ALI, 60 ppm NO diminishes pulmonary vasoconstriction and improves gas exchange by reducing pulmonary venous admixture and alveolar dead space, but does not prevent a fall in Crs. NO inhalation may help prevent long-lasting pulmonary failure.

Administration, Inhalation↗

Effect of positive end-expiratory pressure on intrapulmonary shunt at different levels of fractional inspired oxygen.

In 10 patients undergoing ventilation, venous admixture was measured at different values of positive end-expiratory pressure (PEEP). The measurements were performed at the level of fractional inspired oxygen (FIO2) at which each patient was ventilated, and at FIO2=1. In patients ventilated at FIO2 between 0.21 and 0.3 venous admixture was not modified by PEEP, while in patients ventilated with FIO2 between 0.4 and 0.6, venous admixture decreased significantly (p less than 0.01). With FIO2=1, increased PEEP produced a reduction in venous admixture in all cases (p less than 0.05). These observations suggest that in patients similar to ours, PEEP does not reduce venous admixture at low levels of FIO2 (0.21--0.3), and the observed reduction with PEEP at FIO2=1 may be misinterpreted.

Adult↗

Estimates of African, European and Native American ancestry in Afro-Caribbean men on the island of Tobago.

BACKGROUND/AIMS: The Tobago Afro-Caribbean population is a valuable resource for studying the genetics of diseases that show significant differences in prevalence between populations of African descent and populations of other ancestries. Empirical confirmation of low European and Native American admixture may help in clarifying the ethnic variation in risk for such diseases. We hypothesize that the degree of European and Native American admixture in the Tobago population is low. METHODS: Admixture was estimated in a random sample of 220 men, from a population-based prostate cancer screening survey of 3,082 Tobago males, aged 40 to 79 years. We used a set of six autosomal markers with large allele frequency differences between the major ethnic populations involved in the admixture process, Europeans, Native Americans and West Africans. RESULTS: The ancestral proportions of Tobago population are estimated as 94.0+/-1.2% African, 4.6+/-3.4% European and 1.4+/-3.6% Native American. CONCLUSIONS: We conclude that Tobago Afro-Caribbean men are predominantly of West African ancestry, with minimal European and Native American admixture. The Tobago population, thus, may carry a higher burden of high-risk alleles of African origin for certain diseases than the more admixed African-American population. Conversely, this population may benefit from a higher prevalence of protective alleles of African origin.

Black People↗

Stability and compatibility of cimetidine hydrochloride and aminophylline in dextrose 5% in water injection.

A controlled study was conducted to assess the physical compatibility of cimetidine hydrochloride (HCl) and aminophylline and the chemical stability of an admixture of the two medications in dextrose 5% in water (D5W) injection, over 48 hours at room temperature. Three one-liter admixtures were prepared, each containing cimetidine HCl 1200 mg and aminophylline 500 mg in D5W. One liter of only cimetidine HCl 1200 mg in D5W and one liter of only aminophylline 500 mg in D5W served as controls. Samples drawn from the five admixtures and immediately frozen were analyzed for cimetidine and theophylline content at times 0, 1, 6, 24, and 48 hours using high-performance liquid chromatography. Chemical stability of each drug was assessed relative to its time-zero concentration. Samples were also drawn from each test and control solution at every time interval to assess the pH. Admixtures were stored at room temperature out of direct sunlight for the duration of the study, and were visually inspected for color change, turbidity, cloudiness, and precipitation. Recovery of cimetidine and theophylline at all test intervals, pH assessments, and visual inspections of the admixtures showed that cimetidine HCl and aminophylline are both chemically stable and physically compatible for 48 hours at room temperature in one liter of D5W.

Aminophylline↗

Progressive changes in electroencephalographic responses to nitrous oxide in humans: a possible acute drug tolerance.

The possibility of acute tolerance to nitrous oxide was examined during halothane anesthesia in humans. Nitrous oxide was added to the inspired gas twice. The first admixture induced three successive stages of electroencephalogram (EEG): delta-waves lasting for 13 +/- 12 min, theta-waves lasting for 41 +/- 21 min, and, finally, spindle-type waves. The spindle-type EEG was similar to that of halothane anesthesia in configuration, but smaller in amplitude and faster in frequency than that seen during halothane anesthesia. The second admixture, given after a 20-30-min interval, induced a continuous delta-wave EEG in one patient, theta-waves followed by spindle EEG in eight patients, and spindle-type EEG in four patients. The successive changes of electroencephalographic response during the first admixture indicate that an alteration of central nervous system function occurred. The altered state was maintained in the absence of nitrous oxide: responses to a second admixture were characteristic of the later, altered, stages of responses seen after the first admixture. These findings support the view of acute tolerance to nitrous oxide.

Adult↗