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R Sutherland

Publications and source records attributed to R Sutherland.

At least 19 recordsLinked to original sources
PubMed1992

Activity of amoxycillin-clavulanic acid against Legionella pneumophila in vitro and in an experimental respiratory infection model.

Amoxycillin and clavulanic acid show good activity against Legionella pneumophila in vitro, and synergy has been observed between the two agents. However, in tissue culture studies, amoxycillin was inactive against intracellular legionellae, whereas clavulanic acid and amoxycillin plus clavulanic acid were as effective as erythromycin in preventing bacterial growth. These latter findings were reflected in the results of therapy of a L. pneumophila pneumonia in the neutropenic rat. Amoxycillin was ineffective in reducing bacterial counts in the lungs of infected animals, but clavulanic acid and amoxycillin-clavulanic acid produced bactericidal effects similar to those of erythromycin. The data illustrate the bactericidal activity of amoxycillin-clavulanic acid and clavulanic acid against intracellular L. pneumophila in contrast to the lack of activity of amoxycillin.

Amoxicillin↗
PubMed1992

Bactericidal effects of co-amoxiclav (amoxycillin clavulanic acid) against a Legionella pneumophila pneumonia in the immunocompromised weanling rat.

To evaluate the activity of co-amoxiclav (amoxycillin/clavulanic acid) against Legionella pneumophila in vivo, a model of L. pneumophila pneumonia was developed in weanling rats rendered leukopenic by pre-administration of cyclophosphamide. Assessment of therapy was by lung bacterial counts and histological examination. Amoxycillin was ineffective in reducing bacterial counts in the lungs of infected rats, whereas erythromycin, the standard agent, was significantly more effective (P < 0.01). Co-amoxiclav and erythromycin, administered parenterally, produced significant bactericidal effects (P < 0.01), reducing the counts of L. pneumophila strain 1624 at 96 h to 1.2 log10 cfu/lungs compared with counts of 6 log10 cfu/lungs in the untreated animals. Clavulanic acid was also highly effective in preventing development of the infection, and was as efficacious as co-amoxiclav. Because of the significant reduction in bacterial numbers, a marked reduction in inflammation and consolidation of lung tissue was seen in rats treated with erythromycin, clavulanic acid or co-amoxiclav. The activity of co-amoxiclav was no greater than clavulanic acid alone, and no synergy was noted between the two components. When therapy was delayed until 48 h after infection, co-amoxiclav was as effective as erythromycin, with both treatments reducing bacterial numbers to 3.3 and 3.6 log10 cfu/lungs by 96 h, after only two days of therapy, in comparison with non-treated rats (5.6 log10 cfu/lungs). In a prolonged infection, produced by extending the period of leucopenia, co-amoxiclav and erythromycin were equally effective in preventing growth of the organism, with 1.5 and 1.6 log10 cfu/lungs, respectively, present at 96 h, in contrast to the non-treated rats with 5.7 log10 cfu/lungs (P < 0.01). After cessation of therapy, regrowth of L. pneumophila occurred in the erythromycin-treated group to such a degree that by 168 h, lung viable counts from these rats were significantly higher (4.8 log10 cfu/lungs) than in co-amoxiclav-treated rats (2.1 log10 cfu/lungs) (P < 0.05). Oral therapy of this infection with erythromycin or clavulanic acid, either alone or in combination with amoxycillin, resulted in counts of 3.3, 3.6 and 3.5 log10 cfu/lungs at 96 h, respectively. Although oral therapy was significantly less effective than parenteral therapy (P < 0.05), the bacterial counts in the treated groups were significantly lower than in the non-treated animals. The data show that co-amoxiclav displayed bactericidal activity consistently against intracellular L. pneumophila in vivo.

Administration, Oral↗
PubMed1992

The association of pain with physical activities in chronic low back pain.

Most patients with chronic low back pain associate strenuous physical activities with increased pain. This association can cause avoidance of those activities believed to cause intolerable discomfort. This study explored the relationship of performance of physical activities with self-reported pain measures in 40 consecutive patients with disabling low back pain (mean duration 17 months) during a functional restoration rehabilitation program (mean treatment period 7 weeks). Evaluations were performed at initial presentation and at program completion. Measures included quantification of performance on eight physical tests assessing flexibility, lifting capacity and endurance. Before physical testing patients were asked to complete a pain analog scale, a quantified pain drawing, and a rating of the pain anticipated to result from the performance of each physical test. Results showed that pain measures did not generally correlate with measured physical performance. At completion of treatment, significant improvement in performance on all physical tests was found, but these were not associated with consistent changes in pain measures. These results demonstrate that subjects with chronic low back pain can increase their physical performance abilities within their same pain experiences. Medical recommendations for subjects' involvement in physical activities should not be based solely on the reported association of pain with those activities.

Adult↗
PubMed1991

Serologic response to treatment of infectious syphilis.

OBJECTIVE: To evaluate the serologic response to treatment of patients with infectious syphilis. DESIGN: Historical cohort study of all cases of infectious syphilis in Alberta from 1981 to 1987. PATIENTS: A total of 1090 patients were entered; 857 with primary syphilis, 183 with secondary syphilis, and 50 with early latent disease. Two hundred and eight patients were excluded who either were pregnant, had negative serologic results before treatment, had clinical relapse, were treatment failures, or were lost to follow-up. INTERVENTIONS: All 882 evaluable patients were treated with a recommended antibiotic regimen for infectious syphilis and returned for re-assessment including repeat serologic testing. MEASUREMENTS AND MAIN RESULTS: Seventy-two percent (95% CI, 66% to 77%) and 56% (CI, 43% to 70%) of patients with initial episodes of primary or secondary syphilis had seroreverted according to rapid plasma reagin (RPR) test results by 36 months. A 2- and 3-tube decline was seen by 6 and 12 months in primary and secondary syphilis. Early latent syphilis resulted in only a 2-tube decrease at 12 months. Serologic response was not affected by sex, age, race, or sexual orientation. Patients with their first infection were more likely to experience RPR seroreversal than those with repeat infections. The RPR reversal rates also depended on the pretreatment titer and stage of disease. At 36 months, 24% (CI, 20% to 28%) of patients had nonreactive fluorescent treponemal antibody absorption tests (FTA-Abs), and 13% (CI, 11% to 15%) had nonreactive microhemoglutination tests for Treponema pallidum (MHA-TP). CONCLUSIONS: Adequate therapeutic response for syphilis must be based on illness episode and the pretreatment RPR titer. Treponemal tests can demonstrate seroreversion after 36 months, and a negative treponemal test does not rule out a past history of syphilis.

Alberta↗
PubMed1991

Beta-lactamase inhibitors and reversal of antibiotic resistance.

The resistance of bacteria to beta-lactam antibiotics is usually associated with production of the enzyme, beta-lactamase, which inactivates the beta-lactam molecule. In the long search for inhibitors of bacterial beta-lactamase the first clinically useful agent, clavulanic acid, was isolated as a metabolite of Streptomyces clavuligerus. Robert Sutherland describes the background to the demonstration of clinical efficacy of combinations of clavulanic acid and other agents with penicillins which has confirmed beta-lactamase inhibitors as one solution to the problems posed by beta-lactamase-producing bacteria.

Anti-Bacterial Agents↗
PubMed1991

Bactericidal effects of amoxycillin/clavulanic acid against a Legionella pneumophila pneumonia in the weanling rat.

Amoxycillin/clavulanic acid and clavulanic acid have been previously reported to demonstrate bactericidal activity in tissue culture studies against intracellular Legionella pneumophila. A rat model of legionellosis was therefore developed for the purpose of assessing the efficacy of these agents against L. pneumophila in vivo. Therapy by the subcutaneous route was started 12 h after infection when the majority of the bacteria observed in lavage fluid were residing in alveolar macrophages. Treatment with amoxycillin was ineffective in reducing the bacterial counts of L. pneumophila in lung homogenates whereas amoxycillin/clavulanic acid displayed bactericidal effects of the same order as the control antibiotic, erythromycin. Further in-vivo studies are planned to assess the clinical relevance of these findings.

Age Factors↗
PubMed1991

Assessment of a clinical scoring system for detection of immunodeficiency in children with recurrent infections.

From January, 1982, to July, 1990, 51 children with recurrent infections were investigated for immunodeficiency in this department by testing neutrophil function, lymphocyte subsets and serum immunoglobulin and complement concentrations. The prevalence of immune dysfunction within the group was 39% (20 of 51). A previously described clinical scoring system, which aims to identify children with a history of recurrent infection who merit investigation for immunodeficiency was also applied to all 51 children. The scoring system identified only 55% (11 of 20) of those with laboratory-proved immunodeficiency and had a false negative rate of 45% (9 of 20). This latter group included 2 children with severe combined immunodeficiency and 1 with hypogammaglobulinemia, diagnoses that one cannot afford to miss. The system was not sufficiently sensitive to be of use in deciding which child to test for immunodeficiency.

Adolescent↗
PubMed1991

Bactericidal effects of ticarcillin-clavulanic acid against Legionella pneumophila pneumonia in immunocompromised weanling rats.

A model of acute Legionella pneumophila pneumonia in neutropenic weanling rats was developed as a means of assessing the efficacies in vivo of the beta-lactams ticarcillin, ticarcillin-clavulanic acid, and clavulanic acid, agents active against the organism in vitro. Weanling rats were dosed with cyclophosphamide 3 days before and immediately prior to infection by intrabronchial intubation with L. pneumophila. The bacteria persisted in the lungs of untreated animals at high counts (5.0 to 7.0 log10 CFU/g of lung tissue) for up to 168 h after infection, and the histological characteristics of the infection were similar to those of the disease in humans. Transmission electron micrography revealed the presence of L. pneumophila multiplying within alveolar macrophages. Therapy with ticarcillin was ineffective in reducing the bacterial numbers in the lung tissue, whereas ticarcillin-clavulanic acid and clavulanic acid were active, producing bactericidal effects similar to those of erythromycin. The ticarcillin-clavulanic acid combination was significantly more efficacious (P less than 0.01) than corresponding doses of clavulanic acid alone. Synergistic activity between ticarcillin and clavulanic acid against L. pneumophila has been demonstrated in vivo, and the combination showed activity similar to that of erythromycin.

Animals↗
PubMed1990

Interleukin 2-induced tyrosine phosphorylation. Interleukin 2 receptor beta is tyrosine phosphorylated.

Interaction of interleukin 2 (IL2) with its high affinity membrane receptor complex (IL2R) is sufficient to induce proliferation of T lymphocytes. However, the biochemical mechanisms by which IL2 induces this process remain unresolved. The IL2R complex consists of at least two distinct polypeptides that bind IL2, a 75-kDa intermediate affinity subunit (IL2R beta) and a 55-kDa low affinity subunit (IL2R alpha). As indicated by Western blotting with anti-phosphotyrosine-specific antibodies and confirmed by phosphoamino acid analysis, we now demonstrate that interaction of the T cell growth factor interleukin 2 (IL2) with its high affinity receptor on IL2-sensitive human peripheral blood lymphoblasts induces tyrosine phosphorylation of proteins of 92, 80, 78, 70-75, and 57 kDa. IL2 induced tyrosine phosphorylation in YT 2C2 cells which express only the 75-kDa intermediate affinity IL2 binding molecule (IL2R beta) but not in cells which either express only the 55-kDa low affinity IL2 receptor molecule (IL2R alpha) or no IL2-binding sites. Therefore, IL2R beta, in the absence of IL2R alpha, appears sufficient to transduce the transmembrane signal leading to tyrosine phosphorylation. Two different antibodies reactive with phosphotyrosine specifically immunoprecipitated IL2R beta cross-linked to radiolabeled IL2. These findings suggest that IL2R beta is a substrate for the tyrosine kinase which is activated by IL2 binding to its receptor. Thus, like several other growth factor receptors, activation of the IL2R results in an increase in tyrosine phosphorylation with the receptor itself serving as one substrate.

Amino Acids↗
PubMed1990

Development of beta-lactamase inhibitors.

The resistance of bacteria to beta-lactam antibiotics was first associated with the production of the enzyme beta-lactamase as long ago as 1940. Since then, increasing numbers of beta-lactamase-producing bacteria capable of inactivating penicillins and cephalosporins have been isolated clinically. One approach to the problem posed by beta-lactamase-producing bacteria has been to seek substances that function as inhibitors of beta-lactamase and that can be used to protect beta-lactam antibiotics from destruction by the bacterial enzymes. The first clinically available inhibitor was clavulanic acid, a metabolite of Streptomyces clavuligerus that was identified in a screening program for naturally occurring beta-lactamase inhibitors. Clavulanic acid is a potent inhibitor of many bacterial beta-lactamases and has been formulated with amoxicillin and ticarcillin to produce broad-spectrum antibiotic combinations active against beta-lactamase-producing bacteria. After the discovery of clavulanic acid, various compounds have been reported to function as inhibitors of bacterial beta-lactamases, but only sulbactam and its prodrug, sultamicillin, have become available commercially. The success of clavulanic acid has confirmed beta-lactamase inhibitors as one solution to the problem of antibiotic-resistant bacteria.

Ampicillin↗
PubMed1979

Comparative antibacterial activity of azlocillin, mezlocillin, carbenicillin and ticarcillin and relative stability to beta-lactamases of pseudomonas aeruginosa and klebsiella aerogenes.

The antibacterial activities of two ureidopenicillins, azlocillin and mezlocillin, were compared with those of the alpha-carboxypenicillins, carbenicillin and ticarcillin, against a large number of gram-positive and gram-negative bacteria. All four penicillins were active against a wide range of bacteria including Pseudomonas aeruginosa, but there were differences in the antibacterial spectra and in the antibacterial effects demonstrated by the two classes of penicillins. In particular, the minimum inhibitory concentrations of azlocillin and mezlocillin against Klebsiella aerogenes and against P. aeruginosa were greatly influenced by the size of bacterial inoculum tested whereas there was no significant inoculum effect with carbenicillin and ticarcillin. In stability tests, the ureidopenicillins were inactivated rapidly by the beta-lactamases of K. aerogenes and P. aeruginosa whereas the alpha-carboxypenicillins were stable. It seems probable that the inoculum effect seen with azlocillin and mezlocillin in antibacterial tests with K. aerogenes and P. aeruginosa is associated with the instability of the compounds to the beta-lactamases of these bacteria.

Carbenicillin↗