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Biomedical subjects

R Sutherland

Publications and source records attributed to R Sutherland.

At least 109 records · Page 6Linked to original sources

Marrow culture studies in adult acute leukemia at presentation and during remission.

Culture of bone marrow and/or blood cells in a semisolid agar system from 43 adults with acute nonlymphoblastic leukemia at first presentation showed two distinct growth patterns at 14 days. In 53% of patients cells failed to grow (type O), while in the remainder an abnormal growth pattern (type B) with small numbers of diffuse colonies and excessive numbers of cell clusters was seen. The response following chemotherapy was significantly better in the patients whose cells failed to grow. Serial culture studies, performed in 9 patients throughout remissions of 100-1112 days, which had been maintained by intermittent chemotherapy, showed wide fluctuations in proliferative activity. These ranged from no growth to marked proliferation with predominance of clusters and small numbers of diffuse colonies, indistinguishable from the type B pattern seen in 47% of patients at first presentation. The possibility is discussed that the periods of failure to grow, and/or those in which a type B pattern emerged, represented sporadic reactivation of leukemic cells.

Adolescent

Preparation, hydrolysis, and oral absorption of lactonyl esters of penicillins.

Lactonyl esters of ampicillin and other penicillins have been synthesized as prodrugs designed to improve the oral absorption of the parent penicillins. In general, the esters hydrolyzed rapidly in the presence of tissues including blood and certain of the esters were better absorbed than the parent penicillin. The phthalidyl ester of ampicillin [talampicillin (British Pharmacopoeia approved name), BRL 8988] was selected for extended studies. The compound was found to be well absorbed in various animal species and gave ampicillin serum concentrations in fasting human volunteers 2.5-3 times those obtained for ampicillin itself.

Administration, Oral

Smoking and pregnancy.

Smoking is associated with decreased fertility in both males and females, an increased abortion rate, lowered birth weight, an increased still birth rate and probably an increased neonatal death rate. There is also a reduced incidence of maternal hypertension (although the babies are at even greater risk), an increased incidence of ante-partum haemorrhage, impaired brain development and possible teratogenic effects. These effects can be reversed if the mother gives up smoking in pregnancy.

Animals

Preparation, hydrolysis, and oral absorption of alpha-carboxy esters of carbenicillin.

Twelve alpha-carboxy esters of carbenicillin, a parenteral broad spectrum semisynthetic penicillin, were synthesized and examined as potential oral carbenicillin derivatives. The rates at which the esters were hydrolyzed in vitro to carbenicillin by animal and human tissues were compared and the carbenicillin serum levels arising after oral administration of the esters were measured in squirrel monkeys and human volunteer subjects. The alpha-carboxyphenyl ester of carbenicillin [carfecillin (British Pharmacopoeia approved name), BRL 3475] WAS SELECTED FOR FURTHER STUDY AND IS PRESENTLY UNDERGOING CLInical trial.

Absorption

Activity of amoxycillin against enterococci and synergism with aminoglycoside antibiotics.

Amoxycillin was more active in vitro than ampicillin or benzylpenicillin against clinical isolates of enterococci. All 55 strains tested were sensitive to the three penicillins but 15 strains showed a high level of resistance to streptomycin and two of these were also insensitive to kanamycin. All strains were sensitive to gentamicin, which was the most active of the aminoglycoside antibiotics. The penicillins showed pronounced bactericidal activity against the enterococci but failed to sterilise cultures of these organisms. Combinations of penicillins and aminoglycosides invariably produced synergistic bactericidal effects which resulted in sterilisation of cultures of these organisms. Combinations of penicillins and aminoglycosides invariably produced synergistic bactericidal effects which resulted in sterilisation of cultures of enterococci provided that the strain was sensitive to the aminoglycoside moiety of the antibiotic combination. Synergism was not observed with a combination of a penicillin and an aminoglycoside when the enterococcus was resistant to the aminoglycoside. The data reported suggest that amoxycillin may have certain advantages, compared with ampicillin or benzylpenicillin, for the treatment of enterococcal infections.

Amoxicillin

Comparative effects of amoxycillin and ampicillin in the treatment of experimental mouse infections.

Amoxycillin was significantly more active than ampicillin in the treatment of intraperitoneal mouse infections when administered by oral and parenteral routes, although the causal bacteria were equally susceptible in vitro to the two penicillins. Amoxycillin produced higher antibiotic blood concentrations in mice than ampicillin after oral administration, and this was a possible explanation for the superior oral activity of amoxycillin. In contrast, antibiotic blood concentrations were the same for both compounds after subcutaneous injection, but it was demonstrated that amoxycillin was more effective than ampicillin by this route in reducing bacterial counts in the peritoneal cavity and in the blood of mice infected with Escherichia coli. Amoxycillin was also significantly more active than ampicillin in the treatment of infection by intraperitoneal dosing as a result of greater bactericidal activity in infected mice together with the production of higher antibiotic blood levels. The results of these studies on the effects of parental treatment of experimental infections with the two penicillins show that the superior chemotherapeutic activity of amoxycillin was associated with the greater bactericidal activity of amoxycillin in vivo and with differences in the distribution of the two penicillins in the infected animal.

Amoxicillin

Transferable antibiotic resistance in enteropathogenic Escherichia coli between 1948 and 1968.

Enteropathogenic strains of Escherichia coli which had been isolated in the United Kingdom during three periods between 1948 and 1968, namely 1948 to 1951, 1957 to 1960, and 1967 to 1968, were tested for susceptibility to ampicillin, streptomycin, tetracycline, chloramphenicol, and sulphonamides. Antibiotic-resistant strains were tested for their ability to transfer antibiotic resistance to an antibiotic-susceptible strain of E. coli K-12. A relatively high proportion of strains isolated between 1948 and 1951 was resistant to ampicillin, streptomycin, or sulphonamides. None of these strains transferred ampicillin or streptomycin resistance, but sulphonamide resistance was R-factor-mediated in three out of 14 sulphonamide-resistant strains. Resistance to tetracycline and chloramphenicol was rare before 1951 but had become common among enteropathogenic E. coli by 1957. Much of the antibiotic resistance of bacteria isolated between 1957 and 1960 was R-factor-mediated, and transferable resistance was about as prevalent among E. coli isolated between 1957 and 1960 as among strains isolated in 1967 and 1968. Nevertheless, there was no appreciable increase in the overall incidence of antibiotic resistance among these enteropathogenic strains of E. coli between 1957 and 1968, although transferable antibiotic resistance was common during this period. These results do not suggest that the emergence of transferable antibiotic resistance will inevitably lead to the rapid development of antibiotic resistance among this group of bacteria.

Anti-Bacterial Agents

Amoxycillin: a new semi-synthetic penicillin.

Amoxycillin (alpha-amino-p-hydroxybenzylpenicillin) is a new semi-synthetic penicillin with a broad spectrum of antibacterial activity similar to that of ampicillin. Penicillin-sensitive strains of staphylococci, streptococci, and pneumococci were sensitive to concentrations of 0.1 mug or less of amoxycillin/ml. Strains of Haemophilus influenzae were inhibited by a level of 0.5 mug/ml, and most strains of Escherichia coli, Proteus mirabilis, Shigella sonnei, Salmonella species, and Streptococcus faecalis were sensitive to a concentration of 5 mug or less of amoxycillin/ml. Penicillinase-producing strains of Staphylococcus aureus and strains of Pseudomonas aeruginosa, indole-positive Proteus, Klebsiella, and Enterobacter were insensitive to amoxycillin. The new penicillin was bactericidal in activity, as with other penicillins, and its antibacterial activity was not reduced in the presence of serum. After oral administration to volunteer subjects amoxycillin produced serum concentrations twice as high as those obtained with similar doses of ampicillin, and the penicillin was recovered unchanged in high concentrations in the urine. The absorption of amoxycillin was not greatly influenced by food, and administration of probenecid resulted in increased and more prolonged concentrations of amoxycillin in serum.

Administration, Oral

Flucloxacillin, a new isoxazolyl penicillin, compared with oxacillin, cloxacillin, and dicloxacillin.

Flucloxacillin, a new isoxazole penicillin, is active against penicillinase-producing strains of Staphylococcus aureus and is well absorbed in man after oral and intramuscular administration. Compared with isoxazole penicillins in current clinical use-namely, oxacillin, cloxacillin, and dicloxacillin-flucloxacillin has proved as active against Gram-positive cocci, including penicillin-resistant staphylococci. The extent of binding of flucloxacillin to the protein of human serum was similar to that of oxacillin and cloxacillin and less than that of dicloxacillin. In man flucloxacillin given orally produced total and free serum levels higher than those obtained with oxacillin and cloxacillin; total serum levels similar to those of dicloxacillin, and free levels greater than those of dicloxacillin. Similarly, after intramuscular injection the free serum levels of flucloxacillin were higher than those of oxacillin, cloxacillin, and dicloxacillin.

Administration, Oral

Procedures for the assay of carbenicillin in body fluids.

The assay of carbenicillin in clinical specimens is complicated by the fact that carbenicillin also contains a small amount of benzylpenicillin, thereby precluding the use of conventional penicillin assay organisms. This report gives details of a microbiological assay method involving the use of a strain of Pseudomonas aeruginosa which is very sensitive to carbenicillin but insensitive to benzylpenicillin. The outline of a microassay method with this organism is presented, and a method for the assay of specimens containing mixtures of carbenicillin and other antibiotics is described.

Agar