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Biomedical subjects

J D Williams

Publications and source records attributed to J D Williams.

At least 289 records · Page 16Linked to original sources
PubMed1987

In vitro susceptibility of Haemophilus influenzae to cefixime.

The in vitro activity of cefixime against 2,458 clinical isolates of Haemophilus influenzae was determined. All the strains were inhibited by less than or equal to 2 micrograms of cefixime per ml, and the modal MIC was 0.03 micrograms/ml. Activity was unaffected by the presence of beta-lactamase produced by 157 isolates. Nineteen of the twenty-four isolates for which cefixime MICs were greater than or equal to 0.5 micrograms/ml were beta-lactamase negative but showed reduced susceptibility to ampicillin.

Cefixime↗
PubMed1987

In vitro activities of aztreonam, imipenem, and amoxycillin-clavulanate against ampicillin-resistant Haemophilus influenzae.

Two hundred and fifty-seven ampicillin-resistant clinical isolates of Haemophilus influenzae were tested by disk diffusion and MIC determination for susceptibility to aztreonam, imipenem, and amoxycillin combined with clavulanate. The modal MICs and MICs for 50 and 90% of isolates of all three antimicrobial agents for the 157 beta-lactamase-positive strains did not differ significantly from figures obtained with 2,201 ampicillin-susceptible H. influenzae by the same methods. Aztreonam and amoxycillin-clavulanate were less active, as reflected by an increase in these parameters, against 38 beta-lactamase-negative isolates requiring greater than or equal to 4 micrograms of ampicillin per ml for inhibition and 62 strains considered to have an intermediate degree of nonenzymic (intrinsic) resistance to ampicillin (zone diameters of less than 20 mm with 2-micrograms ampicillin disks and MICs of 1 or 2 micrograms/ml). There was no detectable difference in imipenem activity against these 100 strains compared with that observed against the ampicillin-susceptible group. Of the 24 strains requiring at least 4 micrograms of imipenem per ml for inhibition, 13 also showed reduced susceptibility to ampicillin (5 beta-lactamase-positive and 8 beta-lactamase-negative isolates). A lack of correlation between reduced susceptibility to imipenem and the other beta-lactams was observed.

Amoxicillin↗
PubMed1987

Classification of cephalosporins.

Many cephalosporins are now in clinical use. They have a wide range of activity against different species of bacteria and also differ in their pharmacokinetic and metabolic characteristics. This article outlines a basis for comparison and classification of cephalosporins into 4 groups active mainly against: (1) Gram-positive bacteria; (2) Gram-negative rods; (3) Gram-negative rods including Pseudomonas spp.; and (4) Gram-negative rods including Bacteroides spp. Further subdivisions highlight the pharmacological differences.

Cephalosporins↗
PubMed1987

In vitro antibacterial effects of cephalosporins.

Data from many studies on the antibacterial effects of cephalosporins are reviewed. Variations in reports from different workers occur because of the composition of the strains used to carry out determination of minimum inhibitory concentrations (MICs). For this reason, standard MIC50/MIC90 data are used sparingly. Where data are available, the activity has been expressed as the mode activity against fully sensitive strains of a species; and the activity against resistant strains is specified, as far as the data allow, for the mechanisms of resistance exhibited.

Bacteria↗
PubMed1987

Relationship of fetal age at conjunctival exposure of pregnant heifers and Brucella abortus isolation.

Pregnant heifers were exposed by a conjunctival inoculation with 1 X 10(7) colony-forming units of Brucella abortus strain 2308. At parturition, milk and uterine samples from dams plus samples from dead calves were cultured bacteriologically for Brucella. The logistic regression probability of B abortus isolation increased from 0.22 to 0.90, as fetal age at exposure of heifers increased from 60 to 150 gestation days. Strain 2308 was recovered at parturition from 14 (64%) of 22, 17 (71%) of 24, and all 28 (100%) heifers that were at gestation days less than 127, 127 to 157, and greater than 157, respectively, at time of exposure. The number of infected heifers and the number of samples positive for B abortus were significantly increased as fetal age at exposure of heifers increased from gestation days less than 127 to greater than 157 (chi 2 greater than 10, P less than 0.005).

Animals↗
PubMed1987

An in vitro system for studying cartilage degradation by macrophages.

Cartilage damage in inflammatory arthritis may be mediated by a number of cell types; the macrophage is one of them. To examine their role we developed a new macrophage-cartilage co-culture system on a microscale. This used macrophages derived from the peritoneal cavity of Balb/c mice together with cartilage slices from bovine nasal septa. We examined the effects of macrophages on cartilage proteoglycan loss measured colorimetrically. When chondrocytes were dead, cartilage released proteoglycan; macrophages increase the amount of proteoglycan loss; stimulating macrophages with zymosan further increased proteoglycan loss. With live chondrocytes the situation was different. Macrophages only gave a major increase in cartilage proteoglycan loss when stimulated by zymosan. These results show it is possible to establish a simple model of macrophage-induced cartilage degradation. In this a variety of effects given by macrophages can be demonstrated depending on the presence or absence of live chondrocytes.

Animals↗
PubMed1986

Rheumatoid inflammation and joint destruction: cause and effect or parallel phenomena?

Joint damage is a characteristic and important consequence of rheumatoid arthritis; it is usually considered to be a direct result of the inflammatory synovitis. This view implies that by treating actively the synovial inflammation subsequent joint damage will be reduced and the long-term outlook of patients with rheumatoid arthritis thus improved. However, there is relatively little clinical evidence that suppressing inflammation reduces rheumatoid joint damage. An alternative view is that the mechanisms causing inflammation and those leading to joint destruction are parallel processes related only indirectly. Considerable evidence supports such a concept. Clinical studies show radiological progression of the disease occurs despite improvements in measures of joint inflammation and a reduction in the levels of acute phase proteins. Damage can progress in either actively inflamed hot joints or cool swollen joints. Histopathologically the features of rheumatoid synovitis are non-specific, while the radiological pattern of joint damage is very characteristic. There is evidence that lymphocytic infiltration is not a poor prognostic finding, despite it being a typical feature of inflamed joints. Experimental studies also fail to show a close correlation between inflammation and cartilage damage: this is seen in experimental arthritis, coculture in vitro systems, and the air pouch model of cartilage damage. We suggest that attempts to improve the outcome of rheumatoid arthritis should not merely concentrate on controlling inflammation but should also seek to modify the associated connective tissue changes of the disease.

Anti-Inflammatory Agents↗
PubMed1986

Behaviour of TEM-1 beta-lactamase as a resistance mechanism to ampicillin, mezlocillin and azlocillin in Escherichia coli.

Escherichia coli isolates which synthesised the extremely common 'TEM-1' plasmid mediated beta-lactamase were more resistant to the alpha-aminopenicillins, ampicillin, mezlocillin and azlocillin, than were strains which lacked this enzyme. However, many TEM-1+ isolates remained sensitive to therapeutic concentrations of mezlocillin (less than 64 mg/l), whereas virtually none was susceptible to such levels of ampicillin or azlocillin. Transconjugants of E. coli K12 into which we introduced various TEM-1 coding plasmids similarly acquired lower levels of resistance to mezlocillin than to ampicillin and azlocillin. Those which expressed relatively small amounts of enzyme remained sensitive to 64 mg/l of mezlocillin, whereas they were substantially resistant (MIC greater than 64 mg/l) to the other alpha-aminopenicillins. These data suggested that the enzyme afforded weaker protection against mezlocillin than against azlocillin and ampicillin and we attempted to relate this finding to its hydrolytic activity. Extracted TEM-1 beta-lactamase hydrolysed high concentrations of mezlocillin more rapidly than ampicillin and azlocillin; however, mezlocillin was calculated to be the weakest substrate at the low concentrations which are likely to be obtainable in the bacterial cell. These data may partly account for the residual activity of mezlocillin against enzyme producers, but target and permeability factors probably also contribute.

Ampicillin↗
PubMed1986

Pharmacokinetics of ciprofloxacin in healthy volunteers and patients with impaired kidney function.

The pharmacokinetics of ciprofloxacin were studied, in six healthy controls and in 18 patients with varying degrees of renal impairment, after administration of a single 100 mg intravenous dose. Pharmacokinetic parameters were calculated on a two compartment open model. The mean distribution volume was 2.1 (+/- 0.6) l/kg of ideal body weight; it did not correlate significantly with renal function. In the healthy volunteers 57 (+/- 9)% of the drug was eliminated by the kidney and 43% by other pathways. The renal clearance of ciprofloxacin correlated with creatinine clearance (rs = 0.93, P less than 0.001), and urinary excretion of the drug was markedly reduced in patients with the most severe degrees of renal impairment. Plasma clearance correlated with creatinine clearance (rs = 0.50, P less than 0.02). This together with the lack of correlation between non-renal clearance and renal function enables us to suggest an intravenous dosage schedule for patients with renal impairment.

Adult↗
PubMed1986

Failure to detect ampicillin-resistant, non-beta-lactamase-producing Haemophilus influenzae by standard disk susceptibility testing.

We questioned whether the apparent rarity of ampicillin-resistant, non-beta-lactamase-producing (NBLP) Haemophilus influenzae was due to failure of detection. We identified ampicillin-resistant and ampicillin-susceptible H. influenzae by the agar dilution technique, using 10(5)- and 10(3)-CFU inocula. We compared the disk susceptibility of 18 ampicillin-resistant NBLP strains, 13 ampicillin-resistant, beta-lactamase-producing strains, and 10 ampicillin-susceptible strains by using standard 10- and 2-micrograms ampicillin disks on two different media. We also investigated the possibility that disks containing 10 micrograms of clavulanic acid and 2 micrograms of ampicillin could be used to distinguish between the two ampicillin-resistant populations. Using the disk containing 2 micrograms of ampicillin, we correctly differentiated all the ampicillin-resistant isolates from the ampicillin-susceptible isolates on both media (a zone diameter of less than or equal to 15 mm was considered resistant). In contrast, the 10-micrograms ampicillin disk failed to detect 44% (8 of 18) of the ampicillin-resistant NBLP strains (a zone diameter of less than or equal to 19 mm was considered resistant). The MIC of ampicillin with the 10(3)-CFU inoculum correlated better with zone diameters than with the 10(5)-CFU inoculum. A difference in zone diameters of greater than or equal to 8 mm between the disk containing 10 micrograms of clavulanic acid and 2 micrograms of ampicillin and the disk containing only 2 micrograms of ampicillin correctly identified all beta-lactamase-producing strains. We conclude that the 2-micrograms ampicillin disk tests more readily identify ampicillin resistance in H. influenzae than do the 10-micrograms ampicillin disk tests. Future investigation should determine whether this in vitro resistance correlates with clinical treatment failures.

Ampicillin↗
PubMed1986

Generation of leukotrienes by human monocytes pretreated with cytochalasin B and stimulated with formyl-methionyl-leucyl-phenylalanine.

The N-formylated tripeptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) initiated the generation of immunoreactive C-6 sulfidopeptide leukotrienes and of leukotriene B4 (LTB4) in a dose-dependent manner from monolayers of human monocytes pretreated for 10 min with 5 micrograms/ml of cytochalasin B. The EC50 for the immunoreactive C-6 sulfidopeptide leukotrienes was 10(-8) M FMLP and for immunoreactive LTB4 was 5 X 10(-8) M FMLP. The maximal response to FMLP occurred within 10 min, and the sum of the two classes of leukotrienes generated was about 1/6 that obtained from monocytes stimulated with calcium ionophore A23187. The requirement for cytochalasin B in order for FMLP, but not the calcium ionophore, to stimulate leukotriene generation is compatible with the ability of cytochalasin B to augment in other cells certain stimulus-specific transmembrane responses that are not dependent on the integrity of the cytoskeleton. Resolution by reverse phase high performance liquid chromatography of the products released from monocytes pretreated with cytochalasin B and stimulated with FMLP or calcium ionophore yielded a single peak of immunoreactive LTB4 eluting at the same retention time as the synthetic standard; immunoreactive C-6 sulfidopeptide leukotrienes eluted at the retention times of leukotriene C4 (LTC4) and leukotriene D4 (LTD4). [3H]LTB4 was not metabolically altered by monocytes pretreated with cytochalasin B and activated with FMLP in comparison with cells treated with buffer alone, whereas [3H]LTC4 was partially converted to [3H]LTD4. The leukotriene-generating response of monolayers of human monocytes pretreated with cytochalasin B to FMLP is receptor-mediated, as indicated by the inactivity of the structural analog N-acetyl-methionyl-leucyl-phenylalanine and by the capacity of the FMLP receptor antagonist carbobenzoxyphenylalanyl-methionine to inhibit the agonist action of FMLP in a dose-response fashion.

Calcimycin↗