PubMed Health⌕ Search

Biomedical subjects

A K Miller

Publications and source records attributed to A K Miller.

At least 19 recordsLinked to original sources
PubMed1990

Excretion of tolbutamide metabolites in young and old subjects.

Tolbutamide (1 g/70 kg) was administered as a single intravenous dose to 31 healthy, non-smoking, drug-free males between 23 and 87 years old and the total amounts of hydroxy and carboxytolbutamide excreted in 24 h were measured. There was a significant decrease in the urinary recovery of both metabolites with age. The reason for these findings is not known at the present time and may be associated with the decrease in creatinine clearance observed in these subjects or other changes in the pharmacokinetics of tolbutamide which are currently being investigated.

Adult↗
PubMed1989

A systematic approach to examining the patient with nail disease.

The majority of patients who present to the clinician for podiatric care do so because of complaints involving the nail and its surrounding structures. All too often the clinician's examination of the nail is incomplete and in many instances completely overlooked. The authors present a systematic approach to the examination of the patient who presents with nail pathology.

Humans↗
PubMed1987

Managing data quality through automation.

Traditional definitions of data quality deal primarily with individual data sets and the data collection process. Today's standards for ensuring data quality have not changed with respect to the desired results, but have simply been expanded to take advantage of modern technology. Computers are used to acquire, review, store, analyze, and report data. Because each of these steps can be automated, the need for human intervention and manual review is minimized. As a result, the potential for invalid data to reach the data analysis stage has increased significantly. To reduce this potential, efforts must be devoted to developing automated procedures that cover every conceivable validation possibility. Relationships between data and data sets must be well defined [1], and data base support that facilitates ready access to the data for the purpose of analysis must be provided. For small data sets, automation may therefore be impractical; but for large, interrelated data sets, automation is highly desirable. Computer automation has therefore expanded the traditional concept of ensuring data quality to include a complex array of interrelated tasks that must be properly managed to achieve the desired results.

Animals↗
PubMed1984

Physical-chemical compatibility of cromolyn sodium nebulizer solution--bronchodilator inhalant solution admixtures.

Cromolyn sodium nebulizer solution, 1%, is physically and chemically compatible (stable) for up to 60 minutes when mixed in vitro with metaproterenol, isoproterenol, isoetharine, epinephrine, terbutaline, and acetylcysteine inhalant solutions, respectively. Similarly, cromolyn does not adversely affect the stability of the individual bronchodilator/mucolytic drugs in the admixtures. Adding a bronchodilator/mucolytic agent to a cromolyn nebulizer solution should not negatively influence the in vivo efficacy or safety of either active ingredient.

Aerosols↗
PubMed1983

Rapid GC method for quantitation of nifedipine in serum using electron capture detection.

For studying the pharmacokinetics of nifedipine after single doses, a rapid, specific, reliable gas chromatographic assay procedure for nifedipine in serum is developed. Using a single-step solvent extraction or a bonded-phase column extraction and electron capture detection, an assay sensitivity of 10 to 25 ng/ml can be achieved using 0.25 ml of serum. The assay quantitates intact nifedipine and separates it reproducibly from its nitro- and nitrosopyridine derivatives.

Chromatography, Gas↗
PubMed1982

Effects of total plasma concentration and age on tolbutamide plasma protein binding.

Tolbutamide plasma protein binding at different total tolbutamide concentrations was determined in 44 healthy, nonsmoking, drug-free men from 23 to 87 yr old. The data showed that unbound drug increased with total tolbutamide plasma concentration and with age, but that neither the binding equilibrium constant nor the number of binding sites correlated with age. The increase in unbound fraction with age could be partially explained by the decrease in albumin concentration in elderly subjects. Results of multiple linear regression analysis indicated that, although age had a considerably greater influence than albumin concentration, total tolbutamide concentration was the most important determinant of the unbound fraction. Thus, both age and total plasma concentration may affect tolbutamide kinetics.

Adult↗
PubMed1982

Interferences in a high pressure liquid chromatographic assay of theophylline.

Interference by salicylic acid was noted in a high pressure liquid chromatographic assay of theophylline in serum. The acid eluted very close to theophylline in a mobile phase consisting of 0.01 M acetate buffer, pH 4.0, containing 28% methanol on a C-18 reverse-phase column. The two peaks could be resolved by switching to a mobile phase containing 18% methanol, 1.6% acetonitrile, and 1.6% acetic acid in water. However, in this mobile phase traces of the extracting solvent, ethyl acetate, caused a sharpening of the theophylline peak leading to spuriously high results. The problem was overcome by using chloroform to extract the theophylline from serum.

Acetates↗
PubMed1981

Human blood preservation: effect on in vitro protein binding.

In vitro plasma protein binding for phenytoin, meperidine, and bretylium tosylate was affected by the type of preserved human blood used for its estimation. Fresh heparinized plasma and serum gave equivalent fractions bound at the concentrations studied for all three drugs. However, the in vitro plasma binding of phenytoin and meperidine decreased 9-50% when estimated in fresh citrated plasma or commercially available lyophylized human serum at the concentration levels investigated. The fraction of bretylium tosylate bound to plasma protein decreased 30-40% when estimated in fresh citrated plasma but was unchanged when estimated in the lyophylized human serum.

Blood Preservation↗
PubMed1981

Using the Quantimet 720 image analyzing computer to count nucleolated neurones in the human brain.

An approach to the automatic counting of neurones in the human hippocampus is described which uses a modified Quantimet 720 image analyzing computer. Previous work with this and similar machines has attempted to use size alone to discriminate between the various types of cell which are present in any section of central nervous system tissue. Serious errors may then result since agglomerates of small cells and cell fragments can bae confused with single large cells. Instead, 2 electron devices have been designed and built which allow nucleolated neurones, defined as those objects having a grey phase and a black phase both within designated area limits, to be distinguished from all other cells. The mean values for absolute cell numbers and for cell density were within 5% of those obtained by traditional manual methods. The operation of both electronic devices is described and circuit diagrams given for one of them. The other is beyond the scope of this paper, but has been fully reported elsewhere.

Brain↗
PubMed1980

An animal model for assessing pain-on-injection of antibiotics.

The paw-licking response of rats to a subplantar injection of an antibiotic was used as an indicator of the pain caused by that antibiotic. Good agreement with clinical findings was obtained with cefoxitin, cephalothin, cephradine, cefazolin, cephaloridine, and carbenicillin. Incorporation of a local anesthetic into the diluent of an irritating antibiotic reduced the number of paw-licking episodes. This rat paw model offers a simple and rapid means of estimating pain-on-injection following intramuscular injection of antibiotics to humans and may be applicable to other drugs as well.

Anesthetics, Local↗
PubMed1979

Urinary metabolites of 3a,4,5,6,7,7a-hexahydro-3-(1-methyl-5-nitro-1H-imidazol-2-yl)-1,2-benzisoxazole in the dog.

The antiprotozoal drug 3a,4,5,6,7,7a-hexahydro-3-(1-methyl-5-nitro-1H-imidazol-2-yl)-1,2-benzisoxazole (I), which exhibits activity against trypanosomiasis, is also antibacterial in vivo. Since the urine from a dog dosed with I showed a broader spectrum of antibacterial activity than I itself, metabolites from this urine were isolated and partially characterized. The metabolites were mono- and dihydroxy-substituted species with the hydroxyl groups on carbons 4--7 of the hexahydrobenzisoxazole ring. These observations led to the synthesis of several such hydroxy derivatives of I, and their properties fully supported the proposed positions of metabolic hydroxylation. One synthetic compound, the 6,7-cis-dihydroxy compound, exhibited higher antibacterial activity against Salmonella schottmuelleri in mice and greater trypanocidal activity in vivo against Trypanosoma cruzi (Brazil strain) than I.

Animals↗
PubMed1979

Correlation of in vitro susceptibility with in vivo efficacy in mice for cefoxitin in comparison with cephalosporins.

Agar minimal inhibitory concentrations and mouse protection test effective doses were determined for each of four beta-lactam antibiotics against each of 12 Gram-negative and 3 Gram-positive bacterial cultures. The beta-lactamase activity of these cultures also was studied. The data were examined to determine whether relative in vivo efficacies could be predicted from relative in vitro activities. Although such predictions were quite accurate for cefoxitin and cefazolin, this was not true for cefamandole or for cephalothin. Such poor predictability was not necessarily associated with the susceptibility of these cephalosporins to hydrolysis by bacterial beta-lactamases. Although the clinical significance of these observations is not known, these data emphasize that relative in vitro activities should be used only with caution to estimate in vivo efficacies, since not all compounds show the excellent predictability observed here for cefazolin and cefoxitin.

Animals↗
PubMed1979

Thienamycin, a new beta-lactam antibiotic. I. Discovery, taxonomy, isolation and physical properties.

A new beta-lactam antibiotic, named thienamycin, was discovered in culture broths of Streptomyces MA4297. The producing organism, subsequently determined to be a hitherto unrecognized species, is designated Streptomyces cattleya (NRRL 8057). The antibiotic was isolated by adsorption on Dowex 50, passage through Dowex 1, further chromatography on Dowex 50 and Bio-Gel P2, and final purification and desalting on XAD-2. Thienamycin is zwitterionic, has the elemental composition C11H16N2O4S (M.W. = 272.18) and possesses a distinctive UV absorption (lambda max = 297 nm, epsilon = 7,900). Its beta-lactam is unusually sensitive to hydrolysis above pH8 and to reaction with nucleophiles such as hydroxylamine, cysteine and, to a lesser degree, the primary amine of the antibiotic itself. The latter reaction results in accelerated inactivation at high antibiotic concentrations.

Anti-Bacterial Agents↗
PubMed1977

Evidence for a secular increase in human brain weight during the past century.

7397 post-mortem records have been studied. These comphrhend all 20- to 50-year old men and women who had been autopsied in The London Hospital since 1907. Fresh brain weight, body weight and height were abstracted and analysed statistically according to sex and to year of birth, any person with a cerebral or skeletal abnormality having been excluded. Fresh brain weight in men increased gradually by an average of 0-66 g per year from a mean of 1372 g for those born in 1860 to 1424 g in 1940-a total of 52 g. The weight of the female brain increased by 0-28 g per year from 1242 g to 1265 g over the same period. No appreciable rise in fresh brain weight occurred in women until 1900, after which date the increase was of the same order in the two sexes. Evidence of secular increases in body height and in body weight is also given.

Adult↗
PubMed1977

Fosfomycin: Laboratory studies.

Fosfomycin, a nontoxic broad-spectrum antibiotic, different in structure from all previously described antibiotics, acts selectively by inhibiting cell wall formation. It was overlooked during many years of screening because of antagonism by culture medium ingredients and frequent occurrence of resistant mutants. It is effective in many because the neutralizing substances are not present and resistant mutants of most species are avirulent. Fosfomycin has favorable pharmacologic characteristics. It is not cross resistant, does not show antagonism, and has been used successfully in combinations. An insoluble calcium salt is used in oral formulation and a sodium salt for parenteral administration. Overall success rates of 86% were reported with 1,000 patients in Spain and 79% in Japan.

Animals↗