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Biomedical subjects

A K Miller

Publications and source records attributed to A K Miller.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1977

Fosfomycin treatment of Haemophilus influenzae infection in mice.

Haemophilus influenzae is an important pathogen in respiratory infections in children and often is implicated in otitis media. It is sensitive in vitro to a number of antibiotics, some of which are used clinically for the treatment of such infections. We have checked the in vitro sensitivity of a type b strain of H. influenzae. When tested in Levinthal's broth prepared with laked rabbit blood, the culture was most sensitive to tetracycline, ampicillin and penicillin and was somewhat less sensitive to cephalothin, fosfomycin, cephaloridine, and chloramphenicol. However, when this same strain was used to infect mice, fosfomycin was more active than ampicillin, tetracycline, chloramphenicol, penicillin or the cephalosporins.

Ampicillin↗
PubMed1977

The enhancement of beta-lactam antibiotic therapy by novobiocin.

Novobiocin demonstrates an effect similar to that of probenecid (the "probenecid effect") in enhancing the therapeutic efficacy of antibiotics excreted mainly by the renal tubules. The ability of cefoxitin, cephalexin, cephalothin and penicillin G to protect mice against infection with Salmonella schottmuelleri was enhanced 2- to 3-fold when the animals were given oral doses of either probenecid or of novobiocin. The efficacy of cephaloridine, excreted mainly by glomerular filtration, was not enhanced by either probenecid or by novobiocin.

Animals↗
PubMed1974

Cefoxitin, a semisynthetic cephamycin antibiotic: in vivo evaluation.

Cefoxitin, 3-carbamoyloxymethyl-7-alpha-methoxy-7-[2-(2-thienyl)acetamido]-3-cephem-4- carboxylic acid, a semisynthetic cephamycin antibiotic shown to have broad-spectrum activity in vitro, is active also in vivo against a wide variety of bacteria including penicillin-resistant staphylococci. It is, however, particularly effective against gram-negative organisms including strains of indole-positive Proteus against which cephalothin and cephaloridine are ineffective. When cefoxitin is given subcutaneously, concentrations in mouse blood, urine, and other tissues are higher than those seen for cephalothin. Higher concentrations in the blood and greater therapeutic efficacy are achieved with cefoxitin when it is given with probenecid. For this reason it is believed that cefoxitin is excreted mainly by way of the renal tubules. The data indicate that cefoxitin has potential as a therapeutically useful antibiotic.

Animals↗
PubMed1972

Cephamycins, a new family of beta-lactam antibiotics. 3. In vitro studies.

Cephamycins A, B, and C are naturally produced cephalosporin-type antibiotics. Although A and B were found to be more active than C against gram-positive organisms, they were not so active against such strains as are cephalosporin C or the semisynthetic antibiotics cephaloridine and cephalothin. Against gram-negative organisms, cephamycin C was more active than A or B and, in general, was as active as the cephalosporins. In addition, cephamycin C was active in vitro against clinically isolated strains resistant to the cephalosporins, such as Proteus, Providencia, and Escherichia coli. The in vitro antibacterial activity of cephamycin C, cephalothin, and cephaloridine is primarily bactericidal. A 10,000-fold increase in inoculum of a strain of Proteus mirabilis resulted in 200-fold or greater increases in minimal inhibitory and minimal bactericidal end points of cephalothin and cephaloridine, but only 10- and 16-fold increases, respectively, for cephamycin C. After 15 passages through antibiotic-containing broths, during which time a culture of E. coli showed an increase in minimal inhibitory concentrations of streptomycin of >1,000-fold, end points for cephamycin C increased 4-fold, for cephalothin, 1.5-to 6-fold, and for cephaloridine, 128-fold.

Bacteria↗