Search PubMed⌕ Search

Biomedical subjects

J M Hamilton-Miller

Publications and source records attributed to J M Hamilton-Miller.

At least 289 records · Page 16Linked to original sources

Changes in proton-magnetic-resonance spectra during aminolysis and enzymic hydrolysis of cephalosporins.

1. Changes in proton-magnetic-resonance spectra were followed during the reaction of cephalosporins, deacetylcephalosporins, deacetoxycephalosporins and a Delta(2)-cephalosporin with ND(3) in D(2)O. 2. Changes in proton-magnetic-resonance spectra were also followed during the hydrolysis of a cephalosporin and a deacetylcephalosporin in D(2)O with a beta-lactamase. 3. Structures for the reaction products are proposed. 4. The signals obtained after aminolysis of the beta-lactam ring of a cephalosporin indicate that the reaction is accompanied by expulsion of the acetoxy group as acetate, formation of a double bond in the Delta(4)-position and the appearance of an exocyclic methylene group. 5. Aminolysis of deacetyl- and deacetoxycephalosporins can occur without immediate structural changes in the dihydrothiazine ring. 6. In contrast, the ring structure of the first product of enzymic hydrolysis of a deacetylcephalosporin is apparently identical with that of the product of aminolysis of the cephalosporin itself.

Ammonia↗

Damaging effects of ethylenediaminetetra-acetate and penicillins on permeability barriers in Gram-negative bacteria.

1. The permeability barrier against benzylpenicillin has been found to be passive in four strains of penicillinase-producing Gram-negative bacteria (three of Klebsiella aerogenes and one of Escherichia coli). 2. If the three K. aerogenes strains are grown in the presence of sub-inhibitory concentrations of benzylpenicillin, ampicillin or phenethicillin the resultant bacterial cells have deficient permeability barriers. Concentrations of ampicillin or benzylpenicillin less than one-tenth of those required to inhibit growth cause destruction of more than half the permeability barrier in these strains. 3. Benzylpenicillin, ampicillin and phenethicillin have no effect upon the permeability barriers of resting cells from the three K. aerogenes strains. 4. Treatment of resting cells with trisodium EDTA, although failing to sensitize K. aerogenes to lysozyme, severely damages permeability barriers in this species. 5. The magnesium and calcium salts of EDTA do not have the same capacity as the sodium salt for causing damage to permeability barriers in K. aerogenes and E. coli. Damage caused by trisodium EDTA can be at least partially reversed by treatment with Ca(2+) or Mg(2+) ions. It is suggested that EDTA damage is caused by removal of either Ca(2+) or Mg(2+) ions, or both, from the bacterial cell envelope. 6. Bacterial cells with deficient permeability barriers as a result of either growth in the presence of a penicillin or treatment with EDTA remain viable, and revert to their usual permeability after growth in nutrient broth.

Ampicillin↗

Penicillinacylase.

Explore the source record for details and available documents.

Aminohydrolases↗

Rifaprim (rifampicin plus trimethoprim): pharmacokinetics and effects on the normal flora of man.

Ten healthy volunteers were given 'Rifaprim' in the dosage recommended for the treatment of urinary infections in man (rifampicin 300 mg + trimethoprim 80 mg in the morning and double these amounts at night, for 7 days). Levels of both drugs in the serum and urine were determined on the first and last days. The results show that trimethoprim was always present in the serum in amounts sufficient to suppress the emergence of resistance to rifampicin. In the urine, inhibitory concentrations of each drug were present throughout the course of treatment. Aerobic organisms were largely eliminated from the gut and reappeared after treatment still sensitive to both antibiotics: the anaerobic moiety persisted and became resistant to rifampicin. Changes in nasopharyngeal flora were relatively minor. Thus, this dosage regimen of "Rifaprim' contains enough trimethoprim to prevent the emergence of resistance to rifampicin among urinary pathogens under normal circumstances (i.e. provided the organisms are initially sensitive to trimethoprim).

Adult↗

Bioavailability in human volunteers of three intramuscular formulations of cefonicid: a long-acting cephalosporin.

Three different intramuscular formulations of cefonicid (a new long acting cephalosporin) have been tested for bioavailability in 12 healthy volunteers, using a triple crossover design. No significant differences were detectable between the bioequivalence of the three formulations in terms of area-under-curve and 24-h urinary excretion. However, one of the formulations (A) was absorbed significantly more rapidly from the site of injection, causing higher serum levels for up to 1.5 h after administration. A significantly greater urinary excretion was also found up to 8 h after administration of formulation A. All three formulations were well tolerated, and no side-effects or significant changes in laboratory tests were observed.

Adult↗

Comparative trial of trimethoprim and co-trimoxazole in recurrent urinary infections.

Eighty-nine patients with a history of recurrent urinary infection who required immediate treatment for significant bacteriuria were treated with either trimethoprim (300 mg at night) or with the standard course of co-trimoxazole (two tablets 12-hourly) for seven days. Cure rates one week after the end of treatment were 74.4% and 80.4%, respectively. During the following month the relapse rate was lower in the group given trimethoprim than among those who had received co-trimoxazole. Consequently, the cure rates six weeks after the start of treatment were 71.4% in the trimethoprim group and 58.5% in the co-trimoxazole group. These results suggest that in this type of patient, it may be possible to reduce the incidence of bacteriological relapse by giving antibiotics in larger doses and at less frequent intervals than are at present generally recommended.

Adult↗