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Biomedical subjects

B M Frost

Publications and source records attributed to B M Frost.

14 recordsLinked to original sources

Is in vitro sensitivity of blast cells correlated to therapeutic effect in childhood acute lymphoblastic leukemia?

Our aim is to study whether or not in vitro sensitivity of leukemic cells correlates with clinical effect; if so, in vitro testing might used for stratification of treatment. During 1995-1997 bone marrow samples from 145 Swedish children with newly diagnosed acute lymphoblastic leukemia were analysed by the automated fluorometric microculture cytotoxicity assay. Therapeutic effect was evaluated by bone marrow morphology day 15 and 29. Preliminary results indicate that marrow samples from patients with poor response to induction therapy show a higher degree of in vitro resistance to several cytotoxic drugs at diagnosis than good responders.

Antineoplastic Agents↗

In vitro cytotoxic drug activity and in vivo pharmacokinetics in childhood acute myeloid leukemia.

Since May 1996 all Nordic countries have been participating in a study of childhood acute myeloid leukemia (AML). The aim is to correlate the in vitro sensitivity of leukemic cells and individual plasma concentrations of cytotoxic drugs with clinical effect. Blast cells from bone marrow and/or peripheral blood are tested against a panel of cytotoxic agents using the fluorometric microculture cytotoxicity assay (FMCA). Plasma concentrations of cytotoxic drugs are analysed during induction therapy. Bone marrow samples from the participating centres generally reached the analysing laboratory within 24 hours. 61 out of 71 (86%) samples were successfully analysed, 47 de novo AML and 14 relapses. Relapsing patients tended to have a more resistant test profile than newly diagnosed patients. Steady state plasma levels of doxorubicin, etoposide and 6-thioguanine nucleotide varied about 10-fold between patients. The intra-individual variation was much less, suggesting that dose adjustment based on pharmacokinetic data might be useful in the future.

Amsacrine↗

Polymerase chain reaction-single-strand conformational polymorphism analysis of antigen receptor rearrangements in monitoring therapeutic effect in childhood ALL.

The rearrangement of the immunoglobulin heavy chain (IgH) genes can be used as a marker of cell lineage and clonality. The polymerase chain reaction (PCR) technique using consensus primers for the IgH gene was used for remission and minimal residual disease (MRD) analysis in the follow-up of childhood acute lymphoblastic leukemia (ALL) of B-cell lineage. Single-strand conformational polymorphism (SSCP) was used to distinguish the specific clonal amplicons from the background. The Authors found that, in a series of 22 patients followed-up for 5.3 to 11.1 years, the PCR-SSCP technique could detect at least one rearrangement at initial diagnosis in 21 (95%). All patients who remained in continuous complete remission were PCR-SSCP negative at remission controls. Ten of the 22 patients had one or more bone marrow relapses. The PCR-SSCP method demonstrated MRD in three of them. In 6 of the 7 (86%) of patients with disease recurrence from whom samples were taken within 6 months before a clinically overt relapse, PCR-SSCP became positive. The Authors conclude that PCR-SSCP of a rearrangement marker might have a role as a convenient technique for monitoring emerging relapse. It may also detect unrelated clones or ongoing secondary recombination events during progression. However, PCR-SSCP is not sensitive enough to detect MRD in all patients in whom disease will later recur.

Bone Marrow Transplantation↗

An experimental model for evaluation of antifungal agents in a Trichophyton mentagrophytes infection of guinea pigs.

A Trichophyton mentagrophytes infection of guinea pigs induced by an occlusive procedure is described. The method of evaluation permits comparison of efficacy of antifungal agents which are not tested simultaneously. Activity was demonstrated following topical application of clotrimazole, miconazole, tolnaftate or griseofulvin and oral administration of griseofulvin. Oral ketoconazole had little effect in this dermatophyte model.

Animals↗

Antibacterial activity of heneicomycin.

Heneicomycin is structurally similar to efrotomycin, mocimycin (kirromycin) and X-5108 (goldinomycin). Comparisons were limited because of the small supplies available. All antibiotics show the same in vitro antibacterial spectrum although some test cultures were less sensitive to efrotomycin. Heneicomycin compared favorably with efrotomycin when given subcutaneously or per os against infections with Moraxella bovis and Streptococcus pyogenes. The raid elimination of heneicomycin observed following oral administration may account for its poor activity against a Bordetella bronchiseptica infection where efrotomycin is effective. It appears more like X-5108 than efrotomycin biologically. The disaccharide on efrotomycin may account for the difference observed.

Animals↗

In vitro and in vivo activity of 3-(1-methyl 1-5-nitro-2-imidazolylmethylideneamino)-2-oxazolidinone against Pasteurella.

Furazolidone was more active than 3-(1-methyl)-5-nitro-2-imidazolyl-methylideneamino)-2-oxazolidinone (MABN) against a series of 34 isolates of Pasteurella and 11 of Yersinia (formerly designated Pasteurella). However, the nitroimidazole was superior to furazolidone by both subcutaneous and oral routes against a series of mouse infections incited by strains of Pasteurella. It also was superior to furazolidone and sulfaquinoxaline when administered in the diet against two Pasteurella strains in a fowl cholera model infection in chickens. The good in vitro activity of MABN plus its low toxicity suggest its further study as an agent for fowl cholera and the shipping fever complex of cattle.

Animals↗

Antibacterial activity of efrotomycin.

Efrotomycin is a narrow spectrum antibiotic. Among the genera tested for susceptibility in vitro it is most active against isolates of Moraxella, Pasteurella, Yersinia, Haemophilus, Streptococcus and Corynebacterium. The drug is as active by oral administration as by the subcutaneous route. Blood levels rise rapidly to high concentrations, after oral dosing, and are prolonged. Two peaks occur which may indicate biliary excretion and reabsorption. Urinary excretion is minimal. The high blood concentrations explain, in part, the in vivo activity against pathogens such as Bordetella bronchiseptica which are relatively insensitive in vitro. Oral activity of efrotomycin is an advantage over the related antibiotics. X-5108 and mocimycin.

Animals↗