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Biomedical subjects

R Sutherland

Publications and source records attributed to R Sutherland.

At least 73 records · Page 4Linked to original sources
PubMed1988

Efficacy of amoxycillin/clavulanic acid in experimental Bacteroides fragilis/Escherichia coli mixed infections.

The efficacy of amoxycillin/clavulanic acid was compared with those of metronidazole, cefuroxime, metronidazole/ampicillin, metronidazole/gentamicin and metronidazole/cefuroxime, in experimental mixed infections produced in mice by subcutaneous inoculation of amoxycillin-resistant strains of Bacteroides fragilis and Escherichia coli. The combination of metronidazole/ampicillin failed to inhibit the growth of E. coli, and exerted only a transient effect on the numbers of Bact. fragilis in the groin abscesses. In contrast, amoxycillin/clavulanic acid prevented the development of the infection, eliminating both organisms. Metronidazole and cefuroxime, alone and in combination, were less effective than amoxycillin/clavulanic acid in inhibiting the growth of the infecting organisms. These results demonstrate the clinical potential of amoxycillin/clavulanic acid in prophylaxis, or in the therapy of mixed aerobe/anaerobe infections.

Amoxicillin↗
PubMed1988

Malignant systemic mastocytosis.

Malignant systemic mastocytosis is a rare disorder, a subgroup of the mast cell neoplasms. Its clinical and histological diagnosis is often difficult, especially in patients without cutaneous involvement. We report an unsuspected case who underwent laparotomy complicated by life-threatening hypotension consistent with vasoactive mediator release from mast cells. The subsequent use of two chemotherapy regimens is detailed and both induced transient reduction in disease bulk.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Penetration and binding of radiolabeled anti-carcinoembryonic antigen monoclonal antibodies and their antigen binding fragments in human colon multicellular tumor spheroids.

The binding and penetration of two 125I-labeled anti-carcinoembryonic antigen (CEA) monoclonal antibodies (MAb) and their F(ab')2 and Fab fragments were measured in multicellular spheroids of poorly (HT29) and moderately well differentiated (Co112) human colon adenocarcinomas which express different amounts of CEA. Spheroids cultured in vitro model tumor microenvironments where poor vascular supply may modulate antigen expression and accessibility. The two MAb studied, 202 and 35, were shown previously to react with different CEA epitopes and to have high affinities of 1.2 and 5.8 X 10(9) M-1, respectively. MAb 202 has also been shown to cross-react with antigens present on human granulocytes and normal epithelial cells from human lung and pancreas. Specific binding of intact MAb and fragments of both antibodies was demonstrated for both types of human colon carcinoma spheroids compared to mouse colon carcinoma (CL26) and mammary tumor (EMT6/Ro) spheroids. Total binding of MAb and fragments was greater (1.5- to 2.5-fold) after 4 h compared to 1 h of exposure; the amount of binding compared to control IgG1 was 5- to 30-fold greater after 1-h incubation and 15 to 200 times greater after 4 h. This binding was stable as demonstrated by short and long wash experiments at 37 degrees and 4 degrees C. The binding of F(ab')2 and Fab fragments of the anti-CEA MAb 35 to spheroids of human colon Co112 was almost 2-fold greater than that of the intact MAb. However, for MAb 202, the binding of intact MAb and F(ab')2 was greater than that of Fab fragments. In addition the binding of both intact and F(ab')2 fragments of MAb 202 was greater than that obtained with MAb 35. Specific binding of both antibodies to HT29 spheroids, which express less CEA, was decreased for MAb and fragments of both 202 and 35. Autoradiography and immunoperoxidase experiments were performed to determine the penetration of MAb and fragments after incubation with intact spheroids. Comparisons were made with labeled MAb directly applied to frozen sections of spheroids. F(ab')2 and Fab fragments of both antibodies were bound at the surface of intact spheroids and penetrated to eight to ten cells, but the intact MAb were localized mainly at the spheroid surface and the outer one to three cell layers. There was much less binding at the surfaces of HT29 compared to Co112 spheroids. An enzyme immunoassay using MAb 35 and 202 demonstrated that Co112 spheroids produced about 8-fold more CEA/mg of cell protein than did monolayer cultures.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗
PubMed1987

Evidence following splenic radiotherapy for a highly dynamic traffic of CFU-GM between the spleen and other organs in chronic granulocytic leukaemia.

Five patients with Ph1 +ve chronic granulocytic leukaemia and massive splenomegaly were given induction therapy with splenic irradiation, and their peripheral blood leucocyte count and granulocyte macrophage progenitor (CFU-GM) concentration monitored during the following six hours. In each patient there was a greater fall in CFU-GM than would have been expected from the fall in leucocyte count, but no evidence of a plasma inhibitor was found to explain the disproportionate reduction in CFU-GM. The difference between the estimated and observed decrease in CFU-GM/1 following splenic irradiation indicates a highly dynamic traffic of CFU-GM from the spleen to other organs in chronic granulocytic leukaemia.

Adult↗
PubMed1986

Cellular growth and metabolic adaptations to nutrient stress environments in tumor microregions.

Heterogeneity of cell subpopulation growth was significantly modulated by different oxygen and glucose environments and necrosis in multicellular tumor spheroids of rodent and human origin. PO2 profiles within spheroids measured with microelectrodes showed major differences associated with different oxygen and glucose supply conditions, indicating important interactions of these two substrates affecting oxygen consumption rates and cellular viability. Cellular interactions in association with the development of growth quiescence and differentiation changed oxygen consumption rates and slopes of PO2 profiles within spheroids. Protein synthesis in monolayer cells in culture was severely inhibited when exposed to extreme hypoxia, but certain proteins were synthesized at increased rates. Many of these oxygenated regulated proteins can also be induced by glucose deprivation. The data demonstrate cellular and subcellular changes in tumor models in vitro because of variations in oxygen and glucose supply. Many of these changes would be expected to occur in tumor microregions in vivo and could have important consequences for therapeutic responsiveness.

Animals↗
PubMed1986

Decreased hypoxic toxicity and binding of misonidazole by low glucose concentration.

The modulation of the hypoxic toxicity and binding of Misonidazole (MISO) by glucose and lactate was studied by exposing exponential EMT6/Ro cells to 5 mM MISO under hypoxic conditions. The concentrations of glucose used were 0.015 mM and 5 mM, and the concentrations of lactate were 0, 3 and 10 mM. There was no significant hypoxic toxicity due to MISO in the absence of glucose. However, with 5 mM glucose, after a latent period of 0.5 hours, there was a rapid decrease in cell survival to less than 0.1% at 2.5 hours incubation in 5 mM MISO. The binding of MISO was also increased by glucose. The amount of MISO bound to cells in 0.015 mM glucose leveled off at 2 nmoles MISO/7 X 10(5) cells at 1 hour, whereas the binding in 5 mM glucose continued to increase to more than 5 nmoles MISO/7 X 10(5) cells after 3 hours incubation. There was no detectable effect of lactate on the binding of MISO to the cells either in 0.015 mM or 5 mM glucose. The high affinity of this binding was indicated by the lack of exchange of radioactive MISO with non-radioactive MISO even after 2 hours of incubation. These data showed that glucose concentrations could modify the toxicity and binding of MISO to hypoxic cells.

Animals↗
PubMed1986

Antibacterial effects of ticarcillin/clavulanic acid in animal models of infection.

The therapeutic effects produced by ticarcillin plus clavulanic acid were compared with those of ticarcillin and clavulanic acid separately against infections in the mouse caused by beta-lactamase-producing bacteria. The infections studied included a pneumonia model, a local tissue infection and pyelonephritis. The distribution of ticarcillin and clavulanic acid in infected animals was evaluated by measurement of the concentrations of the substances present at sites of infection. The results showed that both ticarcillin and clavulanic acid were well-distributed in the mouse and at the doses employed were present at the sites of infection at concentrations of the same order as those obtained in man after administration of ticarcillin/clavulanic acid formulations (Timentin). The protection of ticarcillin by clavulanic acid from inactivation by the beta-lactamases produced in vivo by Bacteroides fragilis, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa was demonstrated by the pronounced bactericidal effects produced by the ticarcillin/clavulanic acid combination against the ticarcillin-refractory infections studied.

Animals↗
PubMed1986

Bactericidal effects of ticarcillin-clavulanic acid against beta-lactamase-producing bacteria in vivo.

The comparative efficacies of ticarcillin and ticarcillin plus clavulanic acid have been determined in the mouse against experimental infections caused by ticarcillin-resistant bacteria. The infections studied comprised an intraperitoneal infection, local tissue infections, pyelonephritis, and pneumonia. Both ticarcillin and clavulanic acid penetrated readily to the sites of infection studied and at the doses employed were present at concentrations of the same order as those obtained in humans after the administration of ticarcillin-clavulanic acid formulations (Timentin; Beecham). At these concentrations, the ticarcillin-clavulanic acid combination caused significant bactericidal effects at the sites of infection against the ticarcillin-resistant strains of Bacteroides fragilis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus investigated. The efficacy of ticarcillin plus clavulanic acid against the infections resistant to therapy with ticarcillin demonstrated the beta-lactamase-inhibitory activity of clavulanic acid in vivo.

Animals↗
PubMed1985

Antibacterial activity of ticarcillin in the presence of clavulanate potassium.

The antibacterial effects produced by ticarcillin disodium plus clavulanate potassium, a combination of the broad-spectrum penicillin ticarcillin, and the beta-lactamase inhibitor clavulanic acid as the potassium salt, have been measured in vitro and in experimental infection studies. The presence of clavulanic acid resulted in a significant enhancement of the activity of ticarcillin against a wide range of beta-lactamase-producing bacteria. These included ticarcillin-resistant strains of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, P. vulgaris, Yersinia enterocolitica, and the anaerobe Bacteroides fragilis. In addition, beta-lactamase-producing isolates of Hemophilus influenzae, Branhamella catarrhalis, Neisseria gonorrhoeae, and Staphylococcus aureus were susceptible to ticarcillin and clavulanate. Clavulanic acid did not influence the activity of ticarcillin against ticarcillin-susceptible bacteria. The bactericidal effects of the antibiotic combination were measured in an in vitro kinetic model in which the drug concentrations were varied to simulate those measured in humans after intravenous dosing with ticarcillin (3.0 g) and clavulanate potassium (100 mg clavulanic acid). In these tests, ticarcillin plus clavulanic acid had pronounced bactericidal activity against ticarcillin-resistant bacteria. The protection of ticarcillin by clavulanic acid from inactivation by bacterial beta-lactamases in vivo was demonstrated in experimental infection models in which the efficacy of the ticarcillin plus clavulanic acid combination against infections caused by beta-lactamase-producing bacteria was correlated with the presence of effective concentrations of both antibiotic and inhibitor at the site of infection.

Animals↗
PubMed1985

Bactericidal effects of amoxycillin/clavulanic acid and ticarcillin/clavulanic acid in in-vitro kinetic models.

The bactericidal effects of amoxycillin and ticarcillin in the presence of clavulanic acid against beta-lactamase-producing bacteria were investigated in in-vitro kinetic models. Amoxycillin/clavulanic acid was rapidly bactericidal as a simulated intravenous 1.2 g bolus dose, against a strain of Klebsiella pneumoniae highly resistant to amoxycillin. Similarly, ticarcillin/clavulanic acid at concentrations similar to those achieved with a 30 min iv infusion of ticarcillin/clavulanic acid (5.0 g/200 mg) produced bactericidal effects against a ticarcillin-resistant strain of Pseudomonas aeruginosa. Addition of gentamicin to the system resulted in a further enhancement of activity.

Amoxicillin↗