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Biomedical subjects

R Wise

Publications and source records attributed to R Wise.

At least 127 records · Page 7Linked to original sources

Pharmacodynamic properties of BAY 12-8039 on gram-positive and gram-negative organisms as demonstrated by studies of time-kill kinetics and postantibiotic effect.

Time-kill kinetics of BAY 12-8039 were studied at two inocula against three strains each of Bacteroides fragilis, Escherichia coli, Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pyogenes. The postantibiotic effects of BAY 12-8039 were studied on three strains each of E. coli, S. aureus, H. influenzae, Streptococcus pyogenes, and Streptococcus pneumoniae. The pharmacodynamic data demonstrated that BAY 12-8039 has marked activity against gram-positive and gram-negative organisms (under both anaerobic and aerobic conditions) and anaerobes. BAY 12-8039 also exhibited a postantibiotic effect of >1 h for all strains except one E. coli strain.

Anti-Infective Agents↗

A study to determine the pharmacokinetics and inflammatory fluid penetration of two doses of a solid formulation of the hexetil prodrug of a trinem, sanfetrinem (GV 104326).

The trinem sanfetrinem (GV 104326) was administered as the oral hexetil prodrug GV 118819X in two dose levels to six healthy volunteers. A single dose equivalent to 125 mg of sanfetrinem was administered, followed 6 weeks later by a single dose equivalent to 500 mg of sanfetrinem. The concentrations of the drug in plasma, cantharidin-induced inflammatory fluid, and urine were measured with a microbiological assay. The stability of sanfetrinem was studied in serum and inflammatory fluid. The mean peak concentrations in plasma of 0.77 and 2.47 microg/ml were attained at 1.1 and 2.0 h after the 125- and 500-mg doses, respectively. Mean peak concentrations in inflammatory exudate of 0.26 and 0.86 microg/ml were attained at 2.80 and 2.67 h after the 125- and 500-mg doses, respectively. The mean terminal elimination half-lives in plasma were 1.33 and 1.97 h for the 125- and 500-mg doses, respectively. The half-lives in the inflammatory fluid were 1.66 and 1.74 h for the 125- and 500-mg doses, respectively. The overall penetration of the drug into the inflammatory fluid was 51.4 and 47.0% for the 125- and 500-mg doses, respectively. Mean urine recovery was greater following 500 mg (24.15%) than after 125 mg (18.4%) of sanfetrinem. Sanfetrinem was relatively unstable in the inflammatory exudate in vitro (half-life, 5.5 h), and this could explain the poor penetration of the drug in the inflammatory exudate observed in this study.

Administration, Oral↗

Functional anatomy of a common semantic system for words and pictures.

The relationship between the semantic processing of words and of pictures is a matter of debate among cognitive scientists. We studied the functional anatomy of such processing by using positron-emission tomography (PET). We contrasted activity during two semantic tasks (probing knowledge of associations between concepts, and knowledge of the visual attributes of these concepts) and a baseline task (discrimination of physical stimulus size), performed either with words or with pictures. Modality-specific activations unrelated to semantic processing occurred in the left inferior parietal lobule for words, and the right middle occipital gyrus for pictures. A semantic network common to both words and pictures extended from the left superior occipital gyrus through the middle and inferior temporal cortex to the inferior frontal gyrus. A picture-specific activation related to semantic tasks occurred in the left posterior inferior temporal sulcus, and word-specific activations related to semantic tasks were localized to the left superior temporal sulcus, left anterior middle temporal gyrus, and left inferior frontal sulcus. Thus semantic tasks activate a distributed semantic processing system shared by both words and pictures, with a few specific areas differentially active for either words or pictures.

Adult↗

Global paradox.

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Animals↗

Requirements of von Willebrand factor to protect factor VIII from inactivation by activated protein C.

The interaction of factor VIII with von Willebrand factor (vWF) was investigated on a quantitative and qualitative level. Binding characteristics were determined using a solid phase binding assay and protection of factor VIII by vWF from inactivation by activated protein C (aPC) was studied using three different assays. Deletion mutants of vWF, a 31-kD N-terminal monomeric tryptic fragment of vWF that contained the factor VIII binding site (T31) and multimers of vWF of different size were compared with vWF purified from plasma. We found that deletion of the A1, A2, or A3 domain of vWF had neither an effect on the binding characteristics nor on the protective effect of vWF on factor VIII. Furthermore, no differences in binding of factor VIII were found between multimers of vWF with different size. Also, the protective effect on factor VIII of vWF was not related to the size of the multimers of vWF. A 20-fold lower binding affinity was observed for the interaction of T31 with factor VIII, and T31 did not protect factor VIII from inactivation by aPC in a fluid-phase assay. Comparable results were found for a mutant of vWF that is monomeric at the N-terminus (vWF-dPRO). The lack of multimerization at the N-terminus may explain the decreased affinity of T31 and vWF-dPRO for factor VIII. Because of this decreased affinity, only a small fraction of factor VIII was bound to T31 and to vWF-dPRO. We hypothesized that this fraction was protected from inactivation by aPC but that this protection was not observed due to the presence of an excess of unbound factor VIII in the fluid phase. Therefore, vWF, T31, and vWF-dPRO were immobilized to separate bound factor VIII from unbound factor VIII in the fluid phase. Subsequently, the protective effect of these forms of vWF on bound factor VIII was studied. In this approach, all forms of vWF were able to protect factor VIII against inactivation by aPC completely. We conclude, in contrast with earlier work, that there is no discrepancy between binding of factor VIII to vWF and protection of factor VIII by vWF from inactivation by aPC. The protective effect of T31 was not recognized in previous studies due to its low affinity for factor VIII. The absence of multimerization observed for T31 and vWF-dPRO may explain the low affinity for factor VIII. No other domains than the binding site located at the D' domain were found to be involved in the protection of factor VIII from inactivation by aPC.

Binding Sites↗

Phonological mediation and the graphemic buffer disorder in spelling: cross-language differences?

Caramazza and Miceli's (1990) theory of the organization of the graphemic buffer in writing is assessed by comparing the performance of an English language graphemic buffer patient, AS, with their Italian language patient, LB. In many qualitative and quantitative aspects the writing of the two patients is remarkably similar. However, there is no trace in the writing of AS of the relative preservation in writing words with simple-CV structures over ones with complex-CV structures found in LB, which was the basis for Caramazza and Miceli's hypothesis of an orthographic syllable tier in the organization of the graphemic buffer. Possible differences in the relative salience of syllables between Italian and English and of differences in regularity of the sound-to-spelling transformations in the two languages are considered. It is argued, however, that the fundamental difference may arise through a greater reliance on phonological mediation by LB, with the relatively preserved syllabic level organization in his writing being phonologically rather than orthographically based.

Aged↗

Investigation of the epidemiology of hospital isolates of Acinetobacter anitratus by two molecular methods.

Two hundred and two isolates of Acinetobacter anitratus from 126 patients in 36 wards belonging to 11 specialties of a university teaching hospital were compared by ribotyping and restriction enzyme digest analysis (REA) of total DNA. Forty-six groups were defined by both techniques and there was 96 center dot 5% agreement between the methods for the designation of isolates into groups. Only two groups were endemic and circulating in the whole hospital while others were less common. Burns and intensive therapy units had the highest number of isolates and these were mainly of the two endemic groups while renal dialysis and neonatal units had isolates belonging to the less common groups. Of the 32 patients with multiple isolates, 17 were infected or colonized at different sites by two and up to four groups of A. anitratus. Both ribotyping and REA of total DNA are discriminatory methods for typing A. anitratus, however, the latter is a simpler and more rapid method and it can be used in a routine clinical laboratory.

Acinetobacter↗

Vitamin E and vitamin E-quinone levels in red blood cells and plasma of newborn infants and their mothers.

OBJECTIVE: Vitamin E is a physiological antioxidant and protects cell membranes from oxidative damage. This study has determined whether vitamin E level in RBC of newborns has any relationship with its level in their mothers. We have also examined levels of vitamin E and vitamin E-quinone, an oxidized product of vitamin E, in paired samples of red blood cells (RBC) and plasma of newborns and their mothers. METHODS: Blood was collected from 26 mothers and their full-term placental cords at delivery. Vitamin E and vitamin E-quinone levels were determined in RBC and plasma by HPLC. RESULTS: Newborn-plasma had significantly lower vitamin E levels compared with maternal-plasma both when expressed as nmole/ml (5.5+/-0.4 vs 26.1+/-1.1, p = 0.0001) or nmole/mumole total lipids (1.9+/-0.1 vs 2.6+/-0.1, p = 0.0001). Vitamin E level in the newborn-RBC was similar to that of maternal-RBC when expressed as nmole/ml packed cells (2.77+/-0.14 vs 2.95+/-0.13), but was significantly lower when expressed as nmole/mumole total lipids (0.56+/-0.03 vs 0.64+/-0.04, p = 0.03) from that of maternal-RBC. Vitamin E-quinone levels are significantly elevated in newborns compared with their mothers both in RBC (29.4+/-2.1 vs 24.1+/-1.2, p = 0.04) and plasma (39.9+/-5.3 vs 25.3+/-4.2, p = 0.006) when expressed as nmole/mmole total lipids but not when expressed as nmole/ml. There was a significant correlation of vitamin E between newborn-plasma and newborn-RBC (r = 0.65, p = 0.0002 for nmole per ml packed RBC;r = 0.63, p = 0.0007 for nmole per mumole total lipids). The relationship between maternal plasma and newborn plasma was significant when vitamin E was normalized with nmole/mumole total lipid (r = 0.54, p = 0.007 but not when expressed as nmole/ml (r = 0.09, p = 0.64). However, vitamin E in the RBC of maternal and newborn had significant correlation when expressed as per ml packed cells (r = 0.61, p = 0.001) and per total lipid (r = 0.46, p = 0.02). There was no relationship of vitamin E-quinone levels between RBC and plasma of newborns and their mothers. CONCLUSIONS: Elevated blood levels of vitamin E-quinone suggest increased oxidative stress and utilization of vitamin E in newborns compared to their mothers. Because vitamin E levels in RBC of newborns are lower and significantly related to vitamin E levels in RBC of their mothers, an increase in vitamin E supplementation to mothers during pregnancy may increase vitamin E levels in the newborn and help impede the effect of extrauterine oxygen toxicity.

Erythrocytes↗

Multidrug-resistant Streptococcus pneumoniae.

Antimicrobial resistance in pneumococci is well established. Of major concern is the development of resistance to penicillin; however, reduced susceptibility to other commonly used agents such as chloramphenicol, erythromycin, and tetracycline has also been observed with increasing frequency. We wish to report the isolation of a clinical strain of Streptococcus pneumoniae with intermediate susceptibility to penicillin (minimum inhibitory concentration, 1 mg/L), which was also resistant to numerous other antimicrobial agents.

Anti-Bacterial Agents↗

Distribution of cefdinir, a third generation cephalosporin antibiotic, in serum and pulmonary compartments.

The distribution of a new cephalosporin, cefdinir, in serum, epithelial lining fluid (ELF), bronchial mucosa and alveolar macrophages was studied in 17 adults following a single oral dose of 300 or 600 mg of cefdinir; tissue samples being obtained by diagnostic bronchoscopy approximately 4 h after this dose. Mucosal biopsies were taken, alveolar macrophages harvested by lavage, and ELF volume derived from urea concentrations in bronchial lavage fluid and blood. A microbiological assay for cefdinir was performed in serum, bronchial mucosa, ELF and alveolar macrophages. In patients taking 300 mg of cefdinir, the median concentrations of cefdinir were 2.00 mg/L (range 1.40-8.00) in serum, 0.78 mg/L (range 0-1.33) in bronchial mucosa, and 0.29 mg/L (range 0-4.73) in ELF. In patients taking 600 mg, the median concentrations were 4.20 mg/L (range 3.05-6.40) in serum, 1.14 mg/L (range 0-1.92) in bronchial mucosa, and 0.49 mg/L (range 0-0.59) in ELF. Cefdinir did not penetrate macrophages.

Administration, Oral↗

A review of the penetration of sparfloxacin into the lower respiratory tract and sinuses.

There are a number of potential sites of infection in the lower respiratory tract. This review summaries the nature of these sites and the ways in which antibiotic penetration can be studied. The results of a single-dose and a multiple-dose study of the penetration of sparfloxacin into the respiratory tract are also provided. After a single oral dose of sparfloxacin 400 mg or a 400 mg loading dose on day 1 followed by 200 mg daily for 2 days, sparfloxacin concentrations in the bronchial mucosa, epithelial lining fluid and alveolar macrophages were higher than the corresponding concentrations in serum. Compared with other fluoroquinolones, sparfloxacin achieves higher concentrations at these sites. Sparfloxacin diffusion into maxillary sinus mucosa has been studied in patients with chronic maxillary sinusitis undergoing surgery. High concentrations of sparfloxacin were detected in sinus mucosa 2 to 5 h after administration of a single dose of sparfloxacin 200 or 400 mg.

Anti-Infective Agents↗

A multinational European survey on the in-vitro activity of rufloxacin and other comparative antibiotics on respiratory and urinary bacterial pathogens.

The antibacterial activity of rufloxacin was confirmed against a large number of respiratory and urinary tract pathogens collected in five European countries. In terms of both MIC90 values and percentages of susceptible isolates found, this new quinolone showed useful in-vitro activity against Mycoplasma catarrhalis, Haemophilus influenzae and Klebsiella pneumoniae, with a large proportion of Staphylococcus aureus also covered, while, as expected Streptococcus pneumoniae and Streptococcus pyogenes were not included in its antibacterial spectrum. Rufloxacin was comparable with the other antibiotics against these pathogens with the exception of streptococci. Against these microorganisms, beta-lactams were the most active agents. Against the urinary pathogens the in-vitro activity of rufloxacin is similar to that of norfloxacin although this latter drug is more active in terms of MIC90 values and in percentages of strains inhibited. In many cases more isolates were susceptible to the remaining comparator agents than to rufloxacin. However, there were no significant differences between the numbers of microorganisms inhibited by the various drugs and rufloxacin. The findings of this survey do not seem to modify the general picture which emerged in previous studies and further confirms its useful spectrum in different geographic settings.

Anti-Bacterial Agents↗