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Stability of cisplatin and etoposide in intravenous admixtures.

The stability of various concentrations of etoposide and cisplatin in intravenous admixtures under various storage conditions was studied. Admixtures containing etoposide (200 and 400 micrograms/mL) with cisplatin (200 micrograms/mL) were prepared in 0.9% sodium chloride injection and in 5% dextrose and 0.45% sodium chloride injection. The admixtures were stored in either polyvinyl chloride bags or glass bottles. Mannitol and potassium chloride were added to selected admixtures. Half of the admixtures were protected from light, while the other half were exposed to fluorescent light. All admixtures were stored at room temperature. Samples were visually inspected and assayed for etoposide and cisplatin content by high-performance liquid chromatography within 15 minutes after admixture preparation and after 8, 24, and 48 hours of storage. Etoposide and cisplatin concentrations decreased less than 10% from the initial concentration after eight hours of storage. At 24 hours, the admixtures containing etoposide 400 micrograms/mL and cisplatin 200 micrograms/mL (with additives) in 0.9% sodium chloride injection precipitated. The decrease in etoposide concentrations during the first 24 hours in the rest of the admixtures was less than 10% of the initial concentration. The change in etoposide concentration was related to the type of i.v. solution and the presence of additives. After 24 hours, the change in cisplatin concentrations was less than 10% of the initial concentration, except in the admixtures that precipitated. For cisplatin, the presence of light was related to an increased loss of cisplatin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗

Droperidol stability in intravenous admixtures.

The stability and compatibility of droperidol in small-volume i.v. admixtures was assessed. Droperidol was diluted to a nominal concentration of 1 mg/50 ml in 5% dextrose injection, 0.9% sodium chloride injection, and lactated Ringer's injection in type I glass bottles and polyvinyl chloride bags. Triplicate samples of each admixture were stored under continuous illumination at 27 +/- 2 degrees C. Specimens from each sample were tested by spectrophotometric assay at intervals during storage periods of up to 272 hours for admixtures containing 5% dextrose injection and 0.9% sodium chloride injection and up to 168 hours for admixtures containing lactated Ringer's injection. Between 48 and 168 hours of storage, a 7% increase was observed in droperidol concentration in 0.9% sodium chloride admixtures in polyvinyl chloride bags. A 24% decrease in droperidol concentration in lactated Ringer's admixtures in polyvinyl chloride bags between 24 and 168 hours was attributed to sorption of droperidol by the plastic container. In all admixtures except those containing lactated Ringer's injection in polyvinyl chloride bags, droperidol concentrations throughout the storage period were within 10% of initial concentrations. Droperidol is stable in the admixtures studied for 7 to 10 days in glass bottles. In polyvinyl chloride bags, concentrations in admixtures containing 5% dextrose injection and 0.9% sodium chloride injection are stable for seven days, but concentrations decrease significantly in lactated Ringer's admixtures.

Droperidol↗

Justification of a pharmacy intravenous admixture service in an Australian hospital.

The time and cost of i.v. admixture preparation by hospital pharmacy staff members in an established admixture unit was compared with that by nurses working on wards. The preparation time of antimicrobial admixtures was determined by using a stopwatch. The total cost of preparing an admixture by pharmacy and nursing staff was calculated by combining the respective labor costs (preparation time x average salary rates weighted for overtime) with the cost of disposable items. The mean +/- S.D. time for admixture preparation in the pharmacy was 3.38 +/- 0.38 minutes, whereas preparation by nurses required 14.37 +/- 1.55 minutes. The mean +/- S.D. total cost (in Australian dollars) of admixture preparation was $1.42 +/- 0.34 per dose, and $4.59 +/- 0.46 per dose, respectively. Centralization of admixture preparation would reduce the time required by 18.32 hours for every 100 admixtures prepared, equivalent to an annual cost avoidance of $112,420 for every 100 admixtures prepared each day. Centralizing the preparation of i.v. admixtures in a hospital pharmacy resulted in significant time savings and cost avoidance.

Australia↗

Bayesian analyses of admixture in wild and domestic cats (Felis silvestris) using linked microsatellite loci.

Methods recently developed to infer population structure and admixture mostly use individual genotypes described by unlinked neutral markers. However, Hardy-Weinberg and linkage disequilibria among independent markers decline rapidly with admixture time, and the admixture signals could be lost in a few generations. In this study, we aimed to describe genetic admixture in 182 European wild and domestic cats (Felis silvestris), which hybridize sporadically in Italy and extensively in Hungary. Cats were genotyped at 27 microsatellites, including 21 linked loci mapping on five distinct feline linkage groups. Genotypes were analysed with structure 2.1, a Bayesian procedure designed to model admixture linkage disequilibrium, which promises to assess efficiently older admixture events using tightly linked markers. Results showed that domestic and wild cats sampled in Italy were split into two distinct clusters with average proportions of membership Q > 0.90, congruent with prior morphological identifications. In contrast, free-living cats sampled in Hungary were assigned partly to the domestic and the wild cat clusters, with Q < 0.50. Admixture analyses of individual genotypes identified, respectively, 5/61 (8%), and 16-20/65 (25-31%) hybrids among the Italian wildcats and Hungarian free-living cats. Similar results were obtained in the past using unlinked loci, although the new linked markers identified additional admixed wildcats in Italy. Linkage analyses confirm that hybridization is limited in Italian, but widespread in Hungarian wildcats, a population that is threatened by cross-breeding with free-ranging domestic cats. The total panel of 27 loci performed better than the linked loci alone in the identification of domestic and known hybrid cats, suggesting that a large number of linked plus unlinked markers can improve the results of admixture analyses. Inferred recombination events led to identify the population of origin of chromosomal segments, suggesting that admixture mapping experiments can be designed also in wild populations.

Animals↗

Effects of pH, temperature, concentration, and time on particle counts in lipid-containing total parenteral nutrition admixtures.

It has been standard practice in the United States to separate lipid emulsion from the other components of total parenteral nutrition (TPN) due to the reported instability of admixed intravenous lipid emulsions. Some clinicians, however, have combined all TPN components into one container and administered these admixtures to patients without apparent difficulties. Infusion of all nutrients from one container has many advantages. In this study standard and concentrated admixtures were aseptically prepared using generally accepted guidelines of the nutritional requirements for a 70-kg patient. Treatments of standard and concentrated admixtures consisted of: storing at 4 degrees C without adjusting the pH; increasing the pH to 6.6 and storing at 4 degrees C; increasing the pH to 6.6 and storing at room temperature. Samples were monitored for 3 weeks by means of Coulter Counter analysis, pH determinations, and visual observations. The pH of the admixtures did not change over 3 weeks. Mean counts of particles with sizes between 1.6 and 25.4 mu increased over time for each treatment group. Within treatments, concentrated admixtures had significantly greater particle counts than the corresponding standard admixtures. Within the standard and within the concentrated admixtures, the particle counts were significantly greater for group one than for group three. Particle counts in group two tended to lie between the values of group one and three. Visual signs of emulsion deterioration were greatest in those admixtures in which the pH was not adjusted and occurred earlier in concentrated admixtures.

Amino Acids↗

A coalescent-based estimator of admixture from DNA sequences.

A variety of estimators have been developed to use genetic marker information in inferring the admixture proportions (parental contributions) of a hybrid population. The majority of these estimators used allele frequency data, ignored molecular information that is available in markers such as microsatellites and DNA sequences, and assumed that mutations are absent since the admixture event. As a result, these estimators may fail to deliver an estimate or give rather poor estimates when admixture is ancient and thus mutations are not negligible. A previous molecular estimator based its inference of admixture proportions on the average coalescent times between pairs of genes taken from within and between populations. In this article I propose an estimator that considers the entire genealogy of all of the sampled genes and infers admixture proportions from the numbers of segregating sites in DNA sequence samples. By considering the genealogy of all sequences rather than pairs of sequences, this new estimator also allows the joint estimation of other interesting parameters in the admixture model, such as admixture time, divergence time, population size, and mutation rate. Comparative analyses of simulated data indicate that the new coalescent estimator generally yields better estimates of admixture proportions than the previous molecular estimator, especially when the parental populations are not highly differentiated. It also gives reasonably accurate estimates of other admixture parameters. A human mtDNA sequence data set was analyzed to demonstrate the method, and the analysis results are discussed and compared with those from previous studies.

Algorithms↗

Stability of ranitidine in intravenous admixtures stored frozen, refrigerated, and at room temperature.

The stability of ranitidine in concentrations of 0.5, 1.0, and 2.0 mg/mL in admixtures with commonly used i.v. fluids was studied. The admixture vehicles were 0.9% sodium chloride, 5% dextrose, 10% dextrose, 5% dextrose and 0.45% sodium chloride, and 5% dextrose with lactated Ringer's (DLR) injections in polyvinyl chloride bags. Three bags were prepared for each test solution and stored under each of the following conditions: seven days at room temperature (23 +/- 1 degrees C) in normal laboratory lighting, 30 days at 4 degrees C, and 60 days at -20 degrees C followed by either seven days at room temperature (in light) or 14 days at 4 degrees C. Ranitidine content was determined by high-performance liquid chromatography at several intervals. Color, clarity, and pH were also examined. Ranitidine concentrations remained greater than or equal to 90% of initial concentrations under all storage conditions except in the frozen DLR admixtures. Drug loss in the DLR admixtures was greatest at the lower ranitidine concentrations. The only visual changes were yellow color in the thawed DLR admixtures and those containing ranitidine 2.0 mg/mL in 5% dextrose and 0.45% sodium chloride. Slight increases in the pH of some admixtures were noted. Ranitidine is stable for seven days at room temperature and 30 days at 4 degrees C at all concentrations and in all vehicles studied. At the studied concentrations, the drug is stable in admixtures frozen for 60 days and stored for seven days at room temperature or 14 days refrigerated, except in DLR admixtures; these admixtures should not be stored frozen.

Drug Combinations↗

Personnel time and preparation costs for compounded versus premixed intravenous admixtures in three community hospitals.

Personnel time requirements and costs associated with the ordering, preparation, and administration of manually compounded versus premixed i.v. admixtures were determined at three for-profit community hospitals. The three hospitals, all owned by one corporation, ranged in size from 160 to 239 beds. At each hospital, pharmacists or technicians manually compounded admixtures in glass bottles or plastic bags. Work flow descriptions of the activities involved in the preparation and administration of admixtures were created, and time-motion and work-sampling techniques were used to observe three to five pharmacists or technicians in each hospital over a seven-day period. Drug waste also was monitored. At the conclusion of the baseline study, each hospital switched to the premixed products that they had chosen to evaluate; admixtures of cefazolin sodium, cefoxitin sodium, gentamicin sulfate, and potassium chloride were available. After a two-week acclimation period, the seven-day study was repeated. Average total labor time ranged from 5.6 to 9.1 minutes per compounded admixture to 4.1 to 7.7 minutes per premixed admixture. The percentage of total labor time devoted to compounding, delivering, stocking, and other physical handling of materials decreased by 64% for admixtures of gentamicin or potassium chloride and by 67% for admixtures of cefazolin or cefoxitin. The average reduction in annual costs for accessories, labor time, wasted drugs, and inventory at each hospital was +15,000. Additional savings were realized from overall lower acquisition costs for the premixed products at the study hospitals. The use of premixed i.v. admixtures reduced preparation time and labor and material costs in three small- and medium-sized community hospitals.

Costs and Cost Analysis↗

Stability of cimetidine hydrochloride in a total nutrient admixture.

The stability of cimetidine hydrochloride in a total nutrient admixture was studied. A total nutrient admixture composed of 5% amino acid injection, 20% dextrose injection, and 3% intravenous fat emulsion was prepared aseptically in four 2-L ethylene-vinyl acetate bags. Cimetidine hydrochloride injection was added to three of the admixtures to yield final cimetidine concentrations of 600, 1200, and 1800 mg per 1500 mL of admixture; the fourth admixture served as a control. At 0, 24, and 48 hours, cimetidine content was measured by high-performance liquid chromatography, and the admixtures were tested for pH and visually inspected for signs of creaming, oiling out, or phase separation. Particle-size distribution in the admixtures was compared with that in 20% intravenous fat emulsion. No appreciable changes in cimetidine concentration or pH occurred over 48 hours, and no visual changes were observed. Particle sizes were comparable to those in the 20% intravenous fat emulsion control except in the admixture containing cimetidine hydrochloride 600 mg, which had significantly more particles larger than 9.9 microns at 48 hours. In the total nutrient admixture studied, cimetidine hydrochloride in concentrations up to 1800 mg per 1500 mL was stable for 24 hours at room temperature, and the lipid emulsion was apparently not altered during this period by cimetidine.

Chromatography, High Pressure Liquid↗

Compatibility of furosemide with aminoglycoside admixtures.

The compatibility of furosemide with i.v. admixtures containing each of five different aminoglycosides was studied. Admixtures of amikacin 2 mg/ml, gentamicin 1.6 mg/ml, kanamycin 2 mg/ml, netilmicin 1.5 mg/ml, and tobramycin 1.6 mg/ml (as the sulfate salts) were prepared in both 5% dextrose injection and 0.9% sodium chloride injection in minibags. Furosemide injection 4 ml (40 mg) was then added to each admixture, and the admixtures were examined visually and microscopically for precipitate. The macroscopic and microscopic evaluations were repeated 15 minutes and 24 hours after mixing. To simulate Y-site injection of furosemide, furosemide injection 1 ml (10 mg) was added to 1 ml of each aminoglycoside admixture in a syringe. For admixtures in which precipitates formed, the pH was recorded before and after adding furosemide to subsequent admixtures and also after dropwise addition of 1N sodium hydroxide until the precipitate dissolved. Precipitates were identified using spectrophotometric analysis and melting point determinations. Addition of furosemide resulted in a precipitate only in admixtures containing gentamicin sulfate or netilmicin sulfate; the results for the simulated Y-site injection study were the same. Spectrophotometric analysis and melting point determinations revealed that the precipitate was furosemide. Because furosemide precipitates when added to admixtures containing either gentamicin sulfate or netilmicin sulfate in 5% dextrose injection or 0.9% sodium chloride injection, furosemide should be administered separately or the i.v. tubing should be flushed thoroughly before and after administering this drug via a Y-injection site.

Amikacin↗

Genetic admixture and gallbladder disease in Mexican Americans.

Gallbladder disease is a common source of morbidity in the Mexican American population. Genetic heritage has been proposed as a possible contributor, but evidence for this is limited. Because gallbladder disease has been associated with Native American heritage, genetic admixture may serve as a useful proxy for genetic susceptibility to the disease in epidemiologic studies. The objective of our study was to examine the possibility that gallbladder disease is associated with greater Native American admixture in Mexican Americans. This study used data from the Hispanic Health and Nutrition Examination Survey and was based on 1,145 Mexican Americans who underwent gallbladder ultrasonography and provided usable phenotypic information. We used the GM and KM immunoglobulin antigen system to generate estimates of admixture proportions and compared these for individuals with and without gallbladder disease. Overall, the proportionate genetic contributions from European, Native American, and African ancestries in our sample were 0.575, 0.390, and 0.035, respectively. Admixture proportions did not differ between cases and noncases: Estimates of Native American admixture for the two groups were 0.359 and 0.396, respectively, but confidence intervals for estimates overlapped. This study found no evidence for the hypothesis that greater Native American admixture proportion is associated with higher prevalence of gallbladder disease in Mexican Americans. Reasons for the finding that Native American admixture proportions did not differ between cases and noncases are discussed. Improving our understanding of the measurement, use, and limitations of genetic admixture may increase its usefulness as an epidemiologic tool as well as its potential for contributing to our understanding of disease distributions across populations.

Adult↗

Association of African genetic admixture with resting metabolic rate and obesity among women.

OBJECTIVE: To investigate the role of genetic admixture in explaining phenotypic variation in obesity-related traits in a sample of African-American women (n = 145) and to determine significant associations between obesity traits and admixture genetic markers. RESEARCH METHODS AND PROCEDURES: Associations between genetic admixture and BMI, resting metabolic rate, fat mass, fat-free mass, and bone mineral density were tested using linear regression considering the estimation of admixture by 1) a maximum-likelihood approach (MLA) and 2) a Bayesian analysis. RESULTS: Both the conservative MLA and the Bayesian approach support an association between African genetic admixture and BMI. Evidence for the associations of African genetic admixture with fat mass and fat-free mass was supported by the Bayesian analysis; the MLA supported an association with bone mineral density. When the individual ancestry informative markers that were used to estimate admixture were tested for associations with BMI, significant associations were identified in chromosomes 1, 11, and 12. DISCUSSION: These results provide evidence supporting the application of admixture mapping methods to the identification of genes that result in higher levels of obesity among African-American women. Further research is needed to replicate and further explore these findings.

Apolipoprotein A-I↗

Recombination of haplotypes leads to biased estimates of admixture proportions in human populations.

A population formed by genetic admixture of two or more source populations may exhibit considerable linkage disequilibrium between genetic loci. In the presence of recombination, this linkage disequilibrium declines with time, a fact that is often ignored when considering haplotypes of closely linked systems [e.g., Gm serum group (gamma globulins), HLA, and, more recently, restriction fragment length polymorphisms]. Recombination alters haplotype frequencies over time, and the haplotype-derived measures of admixture proportions from haplotype frequencies in generations following the admixture event become progressively more biased. The direction and extent of this bias can be predicted only when the history of admixture is known. Numerical illustration suggests that this bias is problematic whenever rt greater than 0.05, where r is the recombination rate between linked loci and t is the time (in generations) that has elapsed since the admixture event. In general, even the haplotype frequencies defined by multiple restriction fragment length polymorphism should be used with caution for admixture analysis. When recombination rates or the time since admixture are not precisely known, it is advantageous to consider each restriction fragment length polymorphism site separately for admixture analysis.

Algorithms↗

Admixture studies and the detection of selection.

Three methods can be used to search for evidence of natural selection from admixture studies. These include classification of the admixture estimates into two groups; calculation of the rank correlation between estimates from more than one population; and the testing of admixture estimates for homogeneity. The use of these methods is discussed with special reference to black-white admixture in the United States. Using revised estimates of African gene frequencies, derived from a consideration of the geographical origin of the slaves, we calculated admixture estimates and their variances for five U.S. black populations; Claxton (Georgia); Sapelo Island (Georgia); James Island (South Carolina); Charleston (South Carolina); Oakland (California). Two out of the five populations yielded heterogeneous admixture estimates but all other tests were non-significant. The data provide little evidence for the action of selection. The few, inconsistent significant results are more indicative of the action of random drift or biased gene frequency estimates than natural selection, and in general these effects cannot be differentiated. It seems doubtful that admixture studies can ever provide unequivocal evidence for the action of natural selection in human populations. In the search for natural selection, perhaps admixture studies should only be used as a preliminary screening device.

Black People↗

Spanish genetic admixture is associated with larger V(O2) max decrement from sea level to 4338 m in Peruvian Quechua.

Quechua in the Andes may be genetically adapted to altitude and able to resist decrements in maximal O2 consumption in hypoxia (DeltaVo2 max). This hypothesis was tested via repeated measures of Vo2 max (sea level vs. 4338 m) in 30 men of mixed Spanish and Quechua origins. Individual genetic admixture level (%Spanish ancestry) was estimated by using ancestry-informative DNA markers. Genetic admixture explained a significant proportion of the variability in DeltaVo2 max after control for covariate effects, including sea level Vo2 max and the decrement in arterial O2 saturation measured at Vo2 max (DeltaSpO2 max) (R2 for admixture and covariate effects approximately 0.80). The genetic effect reflected a main effect of admixture on DeltaVo2 max (P = 0.041) and an interaction between admixture and DeltaSpO2 max (P = 0.018). Admixture predicted DeltaVo2 max only in subjects with a large DeltaSpO2 max (P = 0.031). In such subjects, DeltaVo2 max was 12-18% larger in a subgroup of subjects with high vs. low Spanish ancestry, with least squares mean values (+/-SE) of 739 +/- 71 vs. 606 +/- 68 ml/min, respectively. A trend for interaction (P = 0.095) was also noted between admixture and the decrease in ventilatory threshold at 4338 m. As previously, admixture predicted DeltaVo2 max only in subjects with a large decrease in ventilatory threshold. These findings suggest that the genetic effect on DeltaVo2 max depends on a subject's aerobic fitness. Genetic effects may be more important (or easier to detect) in athletic subjects who are more likely to show gas-exchange impairment during exercise. The results of this study are consistent with the evolutionary hypothesis and point to a better gas-exchange system in Quechua.

Adult↗

Compatibility of medications with 3-in-1 parenteral nutrition admixtures.

BACKGROUND: The absence of drug compatibility information with 3-in-1 parenteral nutrition admixtures has been problematic. The purpose of this project was to evaluate the physical compatibility of 106 selected drugs during simulated Y-site injection into nine different 3-in-1 parenteral nutrition admixture formulations. METHODS: Four-milliliter samples of each of the representative 3-in-1 parenteral nutrition admixture formulations were combined in a 1:1 ratio with 4-mL samples of each of 106 drugs, including supportive care drugs, anti-infectives, and antineoplastic drugs. Six replicate samples of each combination were prepared. Two samples were evaluated initially after mixing, two more after 1 hour, and the last two after 4 hours at 23 degrees C. At each test interval, the samples were subjected to centrifugation, causing the fat to rise to the top. The top fat layer and most of the aqueous phase were removed, and the remaining liquid was diluted with about 7 mL of particle-free, high-performance liquid chromatography-grade water to facilitate observation of any particulates that might have formed. Visual examinations were performed in normal diffuse fluorescent laboratory light and under high-intensity, monodirectional light. RESULTS: Most of the drugs tested were physically compatible with the 3-in-1 parenteral nutrition admixtures for 4 hours at 23 degrees C. However, 23 drugs exhibited various incompatibilities with one or more of the parenteral nutrition admixtures. Six drugs resulted in the formation of precipitate with some or all of the admixtures. Seventeen drugs caused disruption of the emulsion, usually with oiling out. CONCLUSIONS: Most of the test drugs were physically compatible with the nine representative 3-in-1 parenteral nutrition admixtures. However, the 23 drugs that resulted in incompatibilities should not be administered simultaneously with the incompatible parenteral nutrition admixtures via a Y injection site.

Amikacin↗

The use of thiopentone/propofol admixture for laryngeal mask airway insertion.

An admixture of thiopentone and propofol was evaluated against propofol for laryngeal mask airway (LMA) insertion. Eighty-one ASA 1 and 2 18- to 65-year-old patients, premedicated with 7.5 mg midazolam orally were assigned randomly to receive either propofol 1% or an admixture of thiopentone and propofol (1.25% and 0.5% respectively), both at a dose of 0.25 ml x kg(-1). Satisfactory conditions for insertion were achieved with the admixture, which was comparable to propofol (73% vs 85%, P>0.05). There was no statistical difference in the incidence or severity of gagging, coughing, inadequate jaw relaxation and laryngospasm. The incidence of hypotension was lower in the admixture group (51% vs 78%, P=0.02). The duration of apnoea was not different between the admixture and propofol group (mean 103s vs 109s respectively, P>0.05). We conclude that thiopentone/propofol admixture can be a suitable alternative to propofol for LMA insertion, producing less hypotension while allowing cost savings of up to 45%. An admixture of thiopentone and propofol (1.25% and 0.5% respectively) can produce suitable conditions compared to propofol 1%, for laryngeal mask insertion. In addition to cost containment, the admixture also produces less hypotension.

Adult↗

[Effect of admixture of betamethasone butyrate propionate ointment on preservative efficacy].

Twenty percent of dermatologists have experienced a separation of water or deterioration of topical corticosteroids mixed with commercially available ointments and/or creams. However, few investigations of this deterioration of admixtures have been reported. To assess the effects of preservatives in preventing microbial contamination of these admixtures, we attempted to investigate the concentration of preservative agents in admixtures and the microbial contamination of these admixtures with a topical corticosteroid ointment (Antebate). The concentration of parabens was reduced by half using an admixture of corticosteroid ointment with four types of moisturizing creams, Urepearl, Pastaronsoft, Hirudoid, and Hirudoidsoft. After a further 3 months, no decrease in parabens was seen. No microbial contamination was found in any admixture stored at room temperature for 1 week and touched two times daily with a finger. The concentration and ratio of the parabens in the aqueous phase and oil phase were entirely different in the admixtures before being centrifuged. The aqueous phase of the admixtures of the oil/water (O/W)-type emulsions of Urepearl and Hirudoid was not found to have microbial contamination immediately after being centrifuged. All aqueous phases stored at room temperature or in a refrigerator for 1 week and touched with a finger twice daily exhibited microbial contamination. These experiments demonstrated that O/W-type emulsions, in which the water easily separates from the bases, should be thoroughly mixed to prevent microbial contamination.

Betamethasone↗