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Biomedical subjects

D M Johnson

Publications and source records attributed to D M Johnson.

At least 19 recordsLinked to original sources

Antibacterial activity of the investigational oral and parenteral cephalosporin BK-218.

BK-218 is a novel cephalosporin with a dual route of administration and spectrum of activity most similar to that of second-generation cephalosporins. BK-218 was active against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis but strains resistant to penicillins had higher MICs. BK-218 had greater activity (8-fold) than cefuroxime or cefaclor against oxacillin-susceptible Staphylococcus spp. Moderate BK-218 activity was observed against Neisseria gonorrhoeae and commonly isolated Enterobacteriaceae such as Escherichia coli (MIC90, 1 mg/l), Klebsiella spp. (MIC90, 2 mg/l), and Proteus mirabilis (MIC90, 2 mg/l). The following organisms were generally BK-218-resistant (MIC90, greater than 16 mg/l): Bacteroides fragilis, Pseudomonas spp., Acinetobacter spp., Xanthomonas maltophilia, Citrobacter spp., Enterobacter spp., indole-positive Proteus, Serratia spp., enterococci and oxacillin-resistant staphylococci.

Cefaclor

Antimicrobial activity of ten macrolide, lincosamine and streptogramin drugs tested against Legionella species.

RP59500, a semisynthetic pristinamycin combination, and 14 other antimicrobial agents were tested against 108 Legionella strains. Of the ten macrolide, lincosamine and streptogramin agents tested, the new streptogramin RP59500 ranked seventh in order of activity against Legionella pneumophila on the basis of MIC90 results as follows: clarithromycin = 14-OH clarithromycin (MIC90 0.12 mg/l) > roxithromycin > erythromycin = tylosin = virginiamycin > RP59500 (MIC90 1 mg/l) = azithromycin > dirithromycin > clindamycin (MIC90 8 mg/l). Of all 14 drugs tested in this study, rifampicin was the most potent with an MIC90 of 0.008 mg/l. In this retrospective study of Legionella strains (1981-1990 isolates), we observed no trend toward resistance to the agents investigated.

Amino Sugars

Antimicrobial activities of two investigational fluoroquinolones (CI-960 and E4695) against over 100 Legionella sp. isolates.

The antimicrobial activities of two investigational fluoroquinolones (CI-960 and E4695) were compared with those of five similar compounds and four comparison drugs against 103 strains of Legionella pneumophila and five other Legionella species type strains. When concentrations inhibiting 90% of strains tested (MIC90s) for L. pneumophila were determined, CI-960 and temafloxacin emerged as the most active (0.015 microgram/ml) and were followed in potency by E4695 (0.03 microgram/ml). This activity was two- to fourfold greater than that of the reference drug, ciprofloxacin, and approached that of rifampin (MIC90, 0.008 microgram/ml). All fluoroquinolones studied were more active than erythromycin (MIC90, 0.5 microgram/ml). These two investigational fluoroquinolones appear well suited for further in vivo study of legionellosis therapy.

Anti-Infective Agents

Antimicrobial activity of isepamicin (SCH21420, 1-N-HAPA gentamicin B) combinations with cefotaxime, ceftazidime, ceftriaxone, ciprofloxacin, imipenem, mezlocillin and piperacillin tested against gentamicin-resistant and susceptible gram-negative bacilli and enterococci.

Isepamicin, formerly SCH21420 or 1-N-HAPA gentamicin B, is an aminoglycoside that was tested alone or in combination with one of seven broad spectrum drugs against 80 clinical isolates. Half of the strains were gentamicin-resistant but only one isolate (1.3%) was resistant to isepamicin. The broadest spectrum comparison drugs tested alone (ciprofloxacin at 3.8% resistance and imipenem at 5.0% resistance) were associated with the lowest synergy rates when combined with isepamicin. The rank order of synergy (complete or partial) was; cefotaxime = ceftazidime = ceftriaxone = mezlocillin = piperacillin (75% to 80%) greater than imipenem (66%) greater than ciprofloxacin (38%). Isepamicin/ampicillin combinations produced synergistic killing of those enterococci not having high-grade resistance to gentamicin or kanamycin. Enterococcus faecium strains were also refractory to isepamicin/ampicillin synergy. Isepamicin appears to be widely useable against gentamicin-resistant gram-negative bacilli either alone or combined with most commonly used broad spectrum beta-lactams.

Cefotaxime

In vitro evaluation of GR69153, a novel catechol-substituted cephalosporin.

GR69153 is a C-7 catechol cephalosporin with a broad spectrum of activity against members of the family Enterobacteriaceae (MICs for 50% of strains tested [MIC50s], 0.008 to 0.5 micrograms/ml), Staphylococcus aureus (MIC50, 4 micrograms/ml), Pseudomonas aeruginosa (MIC50, 0.25 micrograms/ml), Haemophilus influenzae (MIC50, 0.03 micrograms/ml), Neisseria gonorrhoeae (MIC50, 0.03 micrograms/ml), and Acinetobacter spp. (MIC50, 2 micrograms/ml). Potent GR69153 activity was also demonstrated against Moraxella catarrhalis, pneumococci, beta-hemolytic streptococci, gram-positive anaerobes, and most species of coagulase-negative staphylococci. The activity of GR69153 was generally two- to fourfold greater than that of ceftazidime. Resistance level GR69153 MICs for 90% of strains tested (greater than or equal to 32 micrograms/ml) were found most often among Citrobacter freundii, Enterobacter spp. and Morganella morganii strains. GR69153 did not significantly inhibit enterococci, Xanthomonas maltophilia, the Bacteroides fragilis group, Corynebacterium jeikeium, or Listeria monocytogenes. GR69153 was bactericidal and was generally beta-lactamase stable, and MICs were only slightly increased by high inoculum concentrations. Activity was enhanced in an iron-deficient medium, and a modest MIC difference attributed to iron availability was noted between standard agar and broth test results. GR69153 was confirmed to be a potent, catechol-substituted cephalosporin with a spectrum slightly wider than that of ceftazidime, but it was less active than cefpirome or imipenem against some gram-positive pathogens and anaerobes.

Bacteria

Emergency toxicology testing (detection, confirmation, and quantification) of basic drugs in serum by liquid chromatography with photodiode array detection.

We investigated the applicability of liquid chromatography with photodiode array detection as a serum drug screening technique in an emergency toxicology setting. Basic compounds are extracted from alkalinized serum with hexane and chromatographed on a cyanopropyl reversed-phase column. The photodiode array detector records the ultraviolet spectrum of each eluting peak for identification and quantification. More than 30 drugs/metabolites including antidepressants, antihistamines, phenothiazines, and analgesics are detected at their therapeutic concentrations or less. Quantitative run-to-run precision (CV) for antidepressant drugs at low therapeutic concentrations is less than 6%. We evaluated the potential for interference of greater than 140 compounds of clinical interest. In a split-sample study, 151 of 154 positive drug findings by the method were confirmed by alternative techniques (gas chromatography/mass spectrometry and liquid chromatography with either normal-phase or reversed-phase columns). In the three unconfirmed findings, this method detected drugs at concentrations below the limit of identification of the comparison method. Also, 275 samples judged negative by this procedure were negative by a different liquid-chromatographic method.

Analgesics

Comparison of algorithms of testing for use in automated evaluation of sensation.

Estimates of vibratory detection threshold may be used to detect, characterize, and follow the course of sensory abnormality in neurologic disease. The approach is especially useful in epidemiologic and controlled clinical trials. We studied which algorithm of testing and finding threshold should be used in automatic systems by comparing among algorithms and stimulus conditions for the index finger of healthy subjects and for the great toe of patients with mild neuropathy. Appearance thresholds obtained by linear ramps increasing at a rate less than 4.15 microns/sec provided accurate and repeatable thresholds compared with thresholds obtained by forced-choice testing. These rates would be acceptable if only sensitive sites were studied, but they were too slow for use in automatic testing of insensitive parts. Appearance thresholds obtained by fast linear rates (4.15 or 16.6 microns/sec) overestimated threshold, especially for sensitive parts. Use of the mean of appearance and disappearance thresholds, with the stimulus increasing exponentially at rates of 0.5 or 1.0 just noticeable difference (JND) units per second, and interspersion of null stimuli, Békésy with null stimuli, provided accurate, repeatable, and fast estimates of threshold for sensitive parts. Despite the good performance of Békésy testing, we prefer forced choice for evaluation of the sensation of patients with neuropathy.

Algorithms

Intravascular fasciitis: a case report of an intraoral location.

Nodular fasciitis is a benign reactive fibroblastic proliferation which usually arises from the superficial or deep fascia of the extremities and trunk. In 1981 a distinct variant, intravascular fasciitis (IVF), was reported which possessed the same clinical and histological features of more ordinary forms of nodular fasciitis but, in addition, had a striking involvement of associated arteries and/or veins. A case of intraoral IVF is presented and its clinical and histologic features are compared with those of IVF found elsewhere in the body. A brief discussion of etiology and differential diagnostic considerations is also included.

Adult

Individual differences in auditory capabilities. I.

Twenty-eight audiometrically normal adult listeners were given a variety of auditory tests, ranging from quiet and masked thresholds through the discrimination of simple and moderately complex temporal patterns. Test-retest reliability was good. Individual differences persisted on a variety of psychoacoustic tasks following a period of training using adaptive threshold-tracking methods, and with trial-by-trial feedback. Large individual differences in performance on temporal-sequence-discrimination tasks suggest that this form of temporal processing may be of clinical significance. In addition, high correlations were obtained within given classes of tests (as, between all tests of frequency discrimination) and between certain classes of tests (as, between tests of frequency discrimination and those of sequence discrimination). Patterns of individual differences were found which support the conclusion that individual differences in auditory performance are, in part, a function of patterns of independent abilities.

Adolescent

The unprotected parasphenoidal carotid artery studied by high-resolution computed tomography.

A retrospective review was made of 500 consecutive thin-section axial CT scans of the adult sphenoid sinus using contrast enhancement and the bone algorithm to determine whether there was exposure of the cavernous sinus and the carotid arteries along their parasphenoidal course. At least one cavernous-carotid complex that could be considered at risk during sphenoid sinus surgery was seen in 31.4% of the patients. Of this group, 14.4% of the patients had no bony covering on one or both sides at some point along the parasphenoidal course. In 17% the bony covering was so thin it would give minimal, if any, protection from surgical trauma. A patient who had laceration of an unprotected carotid artery with development of post-traumatic aneurysm is discussed.

Aneurysm

Enantiomeric purity of naproxen by liquid chromatographic analysis of its diastereomeric octyl esters.

A sensitive and specific analytical method was developed to determine the enantiomeric purity of naproxen. A simple derivatization of naproxen with (S)-(+)-2-octanol proceeded quantitatively and gave a mixture of diastereomeric esters displaying baseline separation on liquid chromatography. The ratio of these esters was the same as the ratio of enantiomers present in naproxen samples assayed. Reproducibility of the method was excellent.

Chromatography, Liquid

Comparison of trimethoprim-sulfamethoxazole with sulfamethoxazole in urinary tract infections of children.

The effect of trimethorpim-sulfamethoxazole was compared with that of sulfamethoxazole alone in 26 children with urinary tract infection, randomly assigned according to a double-blind procedure to two equally sized groups. TMX-SMX was found to be superior in rendering the urine culture negative for the 3 months after the start of treatment. Also, over 12-month follow-up period there were fewer recurrences in the patients who received TMP-SMX but here the difference between the two groups did not reach statistical significance.

Administration, Oral