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Biomedical subjects

R Wise

Publications and source records attributed to R Wise.

At least 19 recordsLinked to original sources
PubMed1992

Regional response differences within the human auditory cortex when listening to words.

The relationship between activity within the human auditory cortices and the presentation rate of heard words was investigated by measuring changes in regional cerebral blood flow with positron emission tomography. We demonstrate that in the primary auditory cortices and middle regions of the superior temporal gyri there is a linear relationship between the rate of presentation of heard words and blood flow response. In contrast, the blood flow response in an area of the left posterior superior temporal gyrus (Wernicke's area) is primarily dependent on the occurrence of words irrespective of their rate of presentation. The primary auditory cortices are associated with the early processing of complex acoustic signals whereas Wernicke's area is associated with the comprehension of heard words. This study demonstrates for the first time that time dependent sensory signals (heard words) detected in the primary auditory cortices are transformed into a time invariant output which is channelled to a functionally specialised region--Wernicke's area. Wernicke's area is therefore distinguished from other areas of the auditory cortex by direct observation of signal transformation rather than by association with a specific behavioural task.

Adult↗
PubMed1992

The anatomy of phonological and semantic processing in normal subjects.

We assessed brain activation of nine normal right-handed volunteers in a positron emission tomography study designed to differentiate the functional anatomy of the two major components of auditory comprehension of language, namely phonological versus lexico-semantic processing. The activation paradigm included three tasks. In the reference task, subjects were asked to detect rising pitch within a series of pure tones. In the phonological task, they had to monitor the sequential phonemic organization of non-words. In the lexico-semantic task, they monitored concrete nouns according to semantic criteria. We found highly significant and different patterns of activation. Phonological processing was associated with activation in the left superior temporal gyrus (mainly Wernicke's area) and, to a lesser extent, in Broca's area and in the right superior temporal regions. Lexico-semantic processing was associated with activity in the left middle and inferior temporal gyri, the left inferior parietal region and the left superior prefrontal region, in addition to the superior temporal regions. A comparison of the pattern of activation obtained with the lexico-semantic task to that obtained with the phonological task was made in order to account for the contribution of lower stage components to semantic processing. No difference in activation was found in Broca's area and superior temporal areas which suggests that these areas are activated by the phonological component of both tasks, but activation was noted in the temporal, parietal and frontal multi-modal association areas. These constitute parts of a large network that represent the specific anatomic substrate of the lexico-semantic processing of language.

Adult↗
PubMed1992

The cortical localization of the lexicons. Positron emission tomography evidence.

Positron emission tomography was used to investigate changes in regional cerebral blood flow (rCBF) in neurologically normal subjects during word reading and word repetition. The blood flow in these conditions was compared with control conditions where subjects were presented with stimuli of comparable auditory and visual complexity to real words and said the same word on presentation of each stimulus. The control condition for word repetition (hearing spoken words presented backwards) resulted in bilateral activation of the superior temporal gyrus. Word repetition caused a significant increase in rCBF over this control condition in the left superior and middle temporal gyri. The control condition for word reading (seeing stimuli written in 'false fonts', i.e. non-existent letter-like forms) resulted in significant changes in rCBF bilaterally in the striate and extrastriate cortex. Word reading caused a significant increase in blood flow relative to this control in the posterior part of the left middle temporal gyrus. The implications of these results are discussed, and it is argued that they are consistent with localization of a lexicon for spoken word recognition in the middle part of the left superior and middle temporal gyri, and a lexicon for written word recognition in the posterior part of the left middle temporal gyrus.

Adult↗
PubMed1992

Oral cephalosporins.

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Administration, Oral↗
PubMed1992

In-vitro activity of PD 131628, a new quinolone antimicrobial agent.

The in-vitro activity of PD 131628, the active metabolite of the prodrug PD 131112, was compared with that of ciprofloxacin and members of other groups of antimicrobial agents against 701 recent clinical isolates and strains with known mechanisms of resistance. The MIC90s of PD 131628 against the Enterobacteriaceae were between 0.008 and 0.5 mg/L; PD 131628 was one- to four-fold more active than ciprofloxacin against these strains and was four-fold more active than ciprofloxacin against Pseudomonas aeruginosa. Against the Gram-positive species tested, PD 131628 was two- to four-fold more active than ciprofloxacin, inhibiting all strains of Staphylococcus aureus and Streptococcus pneumoniae with 0.5 mg/L or less. PD 131628 was very active against Neisseria spp., Haemophilus influenzae and Moraxella catarrhalis, with MIC90s ranging from 0.004 to 0.008 mg/L. Organisms with decreased susceptibility to other quinolones had decreased susceptibility to PD 131628, but there was no cross-resistance between this class of antimicrobial and other classes. The protein binding of PD 131628 was at most 25% across a broad range of concentrations. The addition of 70% human serum had little effect on the MICs, but caused a two- to eight-fold increase in MBCs.

Anti-Infective Agents↗
PubMed1992

In-vitro activity of tosufloxacin, a new quinolone antibacterial agent.

The in-vitro activity of tosufloxacin (A-61827) was compared with that of temafloxacin, ciprofloxacin and selected members of other groups of antimicrobial agents, against 684 recent distinct clinical isolates and strains with known mechanisms of resistance. Against members of the Enterobacteriaceae, ciprofloxacin was slightly more active than tosufloxacin, which was more active than temafloxacin. The MIC90 of tosufloxacin for all species of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. was less than or equal to 1 mg/L. Tosufloxacin was slightly more active than temafloxacin, and four to eight fold more active than ciprofloxacin, against the Gram-positive species tested. The MIC90 of tosufloxacin for Staphylococcus aureus was 0.12 mg/L, and for Streptococcus pneumoniae was 0.5 mg/L. All strains of Neisseria spp., Haemophilus influenzae and Moraxella catarrhalis were inhibited by tosufloxacin at a concentration of less than or equal to 0.12 mg/L. Tosufloxacin was the most active quinolone against the anaerobic organisms tested. Cross resistance between quinolones was seen, but not between quinolones and other groups of antimicrobials. The protein binding of tosufloxacin across a range of concentrations averaged 60%. Human serum at a concentration of 70% decreased the bactericidal activity of tosufloxacin by about four-fold.

4-Quinolones↗
PubMed1992

The in-vitro activity of two new quinolones: rufloxacin and MF 961.

The in-vitro activity of two new quinolone antimicrobials, rufloxacin and MF 961, together with the desmethylated metabolite of rufloxacin (MF 922) were compared with other orally administered agents against 622 bacterial strains. Against Enterobacteriaceae and Pseudomonas aeruginosa rufloxacin was generally active (MIC90 1-8 mg/L) with the exception of Klebsiella and Serratia spp. (MIC90 32 mg/L and Enterobacter spp. (MIC90) 64 mg/L. The respiratory pathogens Haemophilus influenzae and Moraxella catarrhalis were susceptible to rufloxacin (MIC90 0.5 and 1 mg/L respectively) but Streptococcus pneumoniae was less susceptible (MIC90 32 mg/L). Staphylococcus aureus were susceptible to rufloxacin (MIC90 2 mg/L). The rufloxacin metabolite MF 922 was generally as active as its parent. MF 961 was usually two-fold more active than rufloxacin. All three compounds were four to 16 times less active than norfloxacin, but rufloxacin was as active or somewhat more active than norfloxacin against Staphylococcus spp. Any strains showing decreased susceptibility to other quinolones exhibited cross resistance to these new agents. The MBC of rufloxacin and MF 922 was within one dilution of the MIC and human serum had little effect upon the activity of both agents. The protein binding of rufloxacin and MF 922 at 1 and 10 mg/L were 55% and 63.8% and 30.3% and 32.6% respectively. The activity of rufloxacin against four strains of Chlamydia trachomatis and one strain of Chlamydia pneumoniae was determined. The MICs for C. trachomatis were 4-8 mg/L and 4 mg/L for C. pneumoniae.

Anti-Infective Agents↗
PubMed1992

Concentrations of cefpodoxime in serum and bronchial mucosal biopsies.

Cefpodoxime proxetil is a new orally administered cephalosporin which has a favorable spectrum of activity against respiratory pathogens. Concentrations of cefpodoxime in serum and bronchial mucosal biopsy were measured in 13 patients without active respiratory tract infection undergoing fibreoptic bronchoscopy. Samples were taken between 1 and 6 h after a single oral dose of cefpodoxime proxetil equivalent to 200 mg of cefpodoxime base. In twelve patients who completed the study, mean serum concentrations were 1.7 mg/L (S.E.M. 0.4) and in ten patients mean bronchial biopsy concentrations were 0.9 mg/L (S.E.M. 0.2). The mean penetration was 54% (S.E.M. 6.1). Cefpodoxime was undetectable in biopsies from two patients. The majority of serum and biopsy concentrations were in excess of the MIC90S for Haemophilus influenzae and Streptococcus pneumoniae. Cefpodoxime proxetil may be worthy of further study in clinical trials in patients with respiratory infections.

Administration, Oral↗
PubMed1992

Bronchoalveolar distribution of cefuroxime axetil and in-vitro efficacy of observed concentrations against respiratory pathogens.

The concentrations of cefuroxime in human alveolar macrophages (AM), epithelial lining fluid (ELF), bronchial mucosal biopsies and serum were measured after a single dose, equivalent to 500 mg of cefuroxime base, given in the form of the orally-administered pro-drug, cefuroxime axetil. Fourteen patients undergoing fibreoptic bronchoscopy with bronchoalveolar lavage were studied. The mean ELF concentration was 0.7 mg/L, that of bronchial biopsies was 1.8 mg/kg and that of serum 3.5 mg/L. AM-associated cefuroxime was detected in nine patients. To assess the in-vitro activity of the concentrations achieved at the potential sites of infection, clinical isolates of common respiratory pathogens were exposed to two concentrations of cefuroxime, based on the observed concentrations in ELF and bronchial mucosa. ELF and mucosal site concentrations were effective against Streptococcus pneumoniae (except one strain with reduced susceptibility to benzyl penicillin) and Haemophilus influenzae. The ELF concentration was less effective against Moraxella catarrhalis.

Aged↗
PubMed1992

Asymptomatic heterotopic ovarian pregnancy.

An unruptured heterotopic ovarian pregnancy was diagnosed and managed surgically. We believe this is the first such case in a woman who was asymptomatic at presentation for an unrelated complaint.

Adult↗
PubMed1992

Antimicrobial susceptibilities and beta-lactamase characterization of Capnocytophaga species.

Capnocytophaga species have been associated with a wide variety of infections in both immunocompetent and immunocompromised patients. On the basis of data from antimicrobial susceptibility studies, beta-lactam antibiotics have been considered efficacious therapy. Six of 19 isolates from primarily clinical sources across Canada demonstrated beta-lactamase production, and agar dilution susceptibility testing showed broad resistance to beta-lactam antibiotics. For the beta-lactamase producing isolates, clavulanate reduced the MIC of amoxicillin for 90% of the strains tested by 64-fold. Isolates were highly susceptible to clindamycin, imipenem, and ciprofloxacin. Characterization of the beta-lactamases produced by two of these isolates (Van1 and Van2) was performed. Isoelectric focusing revealed an identical isoelectric point of 5.6 for both enzymes, but they had markedly different relative hydrolysis efficiencies, and different conditions were required to extract the enzymes. This study demonstrates the production of different types of beta-lactamases by Capnocytophaga spp. and suggests the need to screen all clinical isolates of Capnocytophaga spp. for the presence of beta-lactamases.

Anti-Bacterial Agents↗
PubMed1992

In vitro activity of RU 29246, the active compound of the cephalosporin prodrug ester HR 916.

The in vitro activity of RU 29246 was compared with those of other agents against 536 recent clinical isolates. The MICs of RU 29246 for 90% of members of the family Enterobacteriaceae tested (MIC90s) were less than 2 micrograms/ml except those for Morganella spp. (16 micrograms/ml) and Proteus spp. (8 micrograms/ml). RU 29246 was active against Staphylococcus aureus (MIC90, < or = 8 micrograms/ml) and against Staphylococcus saprophyticus and coagulase-negative staphylococci (MIC90s, < or = 2 micrograms/ml). Streptococci and Neisseria gonorrhoeae were highly susceptible to RU 29246, and the activity of the agent against isolates of Streptococcus pneumoniae (MIC90, < or = 0.5 micrograms/ml), Haemophilus influenzae (MIC90, < or = 2 micrograms/ml), and Moraxella catarrhalis (MIC90, < or = 2 micrograms/ml) was comparable to those of the other cephalosporins tested. RU 29246 was insusceptible to hydrolysis by the common plasmid-mediated beta-lactamases (TEM-1 and SHV-1). However, hydrolysis by the new extended-spectrum beta-lactamases (TEM-3, TEM-5, and TEM-9) was detected. Results of the study suggested that RU 29246 should be investigated clinically for use in the treatment of a wide range of infections.

Bacteroides fragilis↗
PubMed1992

Pharmacokinetics and inflammatory fluid penetration of sparfloxacin.

A single 400-mg oral dose of sparfloxacin was given to each of six healthy male volunteers, and the concentrations of the drug were measured in plasma, cantharides-induced inflammatory fluid, and urine over the subsequent 52 h. The mean peak concentration in plasma of 1.6 micrograms/ml was attained at a mean time of 2.7 h postdose. The mean peak concentration in inflammatory fluid of 1.3 micrograms/ml was attained at a mean time of 5 h postdose. The mean elimination half-life in plasma was 17.6 h, and that in inflammatory fluid was 19.7 h. The overall penetration into inflammatory fluid was 117%. Urinary recovery within the first 52 h postdose was 8.8% of the administered dose. Our results indicate that a once-daily dosage of sparfloxacin should be adequate to treat systemic infections caused by most common bacterial pathogens.

Administration, Oral↗
PubMed1992

Pharmacokinetics and tissue penetration of ampicillin and brobactam following oral administration of 2085P.

Eight healthy volunteers received a 1,000-mg single oral dose of 2085P which consisted of 800 mg of pivampicillin and 200 mg of brobactam. Concentrations of ampicillin and brobactam in plasma, inflammatory fluid, and urine were measured over the subsequent 24 h. Pivampicillin and brobactam were moderately rapidly absorbed. The mean (standard deviation) maximum concentration in plasma (Cmax) of ampicillin was 8.2 (1.9) micrograms/ml, and that of brobactam was 2.1 (2.0) micrograms/ml at mean times of 1.9 (0.5) and 2.3 (0.8) h, respectively. The elimination half-lives in plasma were 1.8 (0.5) and 1.6 (2.0) h, respectively. Both agents penetrated the experimentally induced inflammatory fluid, reaching a mean maximum at 3 h. The Cmax of ampicillin was 6.8 (2.3) micrograms/ml, and that of brobactam was 1.0 (0.4) micrograms/ml. The penetration (derived by comparing the area under the concentration-time curve from 0 h to infinity for inflammatory fluid with that for plasma) was 97.3% (26.0%) for ampicillin and 81% (22.3%) for brobactam. The 24-h urinary recovery was 54.2% (16.6%) of the administered dose for ampicillin and 40.2% (11.4%) for brobactam. These data suggest that this combination of beta-lactam and inhibitor should be efficacious in treating infections caused by ampicillin-resistant pathogens.

Administration, Oral↗