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Biomedical subjects

R Cheung

Publications and source records attributed to R Cheung.

At least 55 records · Page 3Linked to original sources

Screening for aminoglycoside auditory toxicity in the old.

1. We have investigated 22 patients receiving gentamicin, mean (s.d.) age 78 (6) years for auditory toxicity, using a standard audiometric technique in a sound-treated room (Study 1). 2. Use of a portable audiometer might allow a larger and more representative proportion of patients treated with aminoglycosides to be screened for ototoxicity. A method for detecting high frequency loss suitable for use in the ward was evaluated in 12 volunteers aged 27 (4) years (Study 2). 3. The error inherent in taking hearing at the start of treatment as a reference point was measured in 16 patients, aged 81 (8) years, prescribed non-ototoxic antibacterials (Study 3). 4. A significant (P = 0.05) reduction in hearing threshold was detected in Study 1, although psychometric tests revealed unchanged or improved ability to co-operate. This occurred only at 4000 Hz, the highest frequency used. The magnitude of this loss, mean 2.5 dB, was similar to that of the improvement in threshold detected (P = 0.0004) early in the course of treatment in Study 3. Thus, underestimation of ototoxicity is likely. 5. If a change of threshold of 10 dB or more is taken arbitrarily to represent a real change in hearing, then there was a significant excess of patients in Study 1 with losses at 4000 Hz only (P = 0.032). The six with such losses at this frequency were older than the rest. However, there was a significant (P less than 0.02) positive correlation between log mean predose serum gentamicin concentration and age. Thus, it remains to be determined whether presbyacusis sensitizes those hair cells which it does not destroy to toxic damage. 6. The cumulative dose of gentamicin (for a course of the duration given) was calculated according to published prescribing aids. There was no systematic reduction in the ratio of the dose recommended by a given aid to the dose prescribed in the six with hearing losses as defined above. 7. In Study 2, thresholds obtained at 6000 Hz in the open ward were, on average, 0.9 dB higher than in the sound treated room, but the effect of venue did not reach statistical significance. In the morning thresholds were marginally, but significantly (P = 0.04), lower than in the afternoon. Precision, as measured by the standard deviation of replicate determination, was independent of test conditions. Using multiple (ten) threshold determinations appeared to improve resolution.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Compliance with anti-tuberculous therapy: a field trial of a pill-box with a concealed electronic recording device.

We have conducted a field trial of a pill-box containing a concealed electronic device for monitoring compliance in 23 consecutive adult out patients taking a rifampicin/isoniazid combination once daily. In 22 cases, the times when the box was opened were successfully recorded for the entire period (mean (SD) 26 (5) days) between successive clinic visits. In the other patient the record terminated after one week, a broken box being returned. Both totality of compliance (as assessed by box openings) and consistency of compliance (the proportion of the total number of intervals between openings which were of 22 to 26 h in length) were significantly greater in those studied in the intensive than in the maintenance phase of therapy. Patients may have taken the reduction in medication at the end of the intensive phase as signalling cure. A computer program has been developed to display the recorded data. This allowed the physician responsible to assimilate at a glance the patient's tablet-taking habits. In routine practice knowledge of the presence of the device may improve compliance and a discussion of the graphical display may prove of value in counselling.

Adult↗

A family outbreak of hemolytic-uremic syndrome associated with verotoxin-producing Escherichia coli serotype O157:H7.

All five siblings (three boys and two girls, aged 1.5-9 years) in a family developed hemolytic-uremic syndrome associated with verotoxin-producing Escherichia coli O157:H7 at a lakeside vacation cottage during the fall of 1985. All five were hospitalized and made a full recovery. Both parents remained asymptomatic, and neither had evidence of this infection. In four children who were investigated prospectively, free verotoxin was still detectable in the stools for between 3 and 7 weeks. The prodromal diarrheal illness in the children occurred over a 10-day period. The epidemic curve was consistent with a point-source outbreak, but continuous exposure or person-to-person transmission could not be ruled out. The source of the infection was not identified.

Bacterial Toxins↗

The paradox of using a 7 day antibacterial course to treat urinary tract infections in the community.

1. We have studied determinants of outcome of 7 day courses of treatment in 77 middle aged and elderly patients, in whom the general practitioner's diagnosis of urinary tract infections had been confirmed microbiologically. Bacteria were sensitive to cephalexin or trimethoprim. Where there was no preference, treatments were allocated randomly. Compliance was monitored using a pill box with a concealed electronic device which recorded openings of the box. 2. Prescribing trimethoprim, 200 mg twice daily, was more effective than cephalexin, 250 mg four times daily (cure rates 93 and 67%) (P less than 0.006). Those cured and not cured were not distinguished by age, gender, genitourinary history, or infecting organism. 3. Compliance as measured by box openings was worse for cephalexin than for trimethopim (P = 0.01). However, both totality and pattern of compliance were similar in patients cured and not cured by cephalexin. Thus rigid adherence to a conventional course did not promote cure: fewer doses could have been prescribed. 4. Estimating compliance is essential to clinical trials where medication is self-administered. Poor compliance may establish over exacting regimens. Counting box openings did overestimate compliance, but counting residual tablets overestimated it grossly: given the number of openings less than the ideal, there should have been 171 residual tablets, only 55 were found.

Aged↗

Susceptibility of Gardnerella vaginalis to metronidazole, its bioactive metabolites, and tinidazole.

The susceptibilities of 510 clinical isolates of Gardnerella vaginalis to metronidazole, its principal oxidative metabolites, and tinidazole were determined by an agar dilution method. The hydroxy metabolite was the most active, with an MIC90 value (minimum concentration that inhibited 90% of the strains) of 1.12 mg/L (5.51 mumol/L). Tinidazole and metronidazole were somewhat less active, with MIC90s of 4.09 mg/L (23.9 mumol/L) and 4.44 mg/L (18.0 mumol/L), respectively. The acid metabolite was inactive, with an MIC90 value of 226.55 mg/L (1.22 mmol/L). These results suggest that the hydroxy metabolite of metronidazole may contribute significantly to the antimicrobial effect of the parent drug in G. vaginalis-associated infections.

Adult↗

Effects of cycloheximide and puromycin on cytotoxic activity of Escherichia coli verocytotoxin (Shiga-like toxin).

Verocytotoxin (VT)-producing Escherichia coli is closely associated with hemorrhagic colitis and hemolytic uremic syndrome. The diagnosis of this infection requires the demonstration of VT activity in fecal filtrates or the isolation of VT-producing E. coli from stools. To improve the sensitivity of the Vero cell assay for detecting VT, we investigated the interaction between this toxin and cycloheximide and puromycin, agents which, like VT and the related Shiga toxin, are protein synthesis inhibitors. Cycloheximide-treated cells were found to be about eightfold more sensitive to VT, this effect being most pronounced when the drug was added before the toxin. In contrast, puromycin treatment had an antagonistic effect in that it decreased the sensitivity of the cells to VT. In assays of VT in fecal filtrates, the addition of cycloheximide (at 4 to 8 micrograms/ml) increased the sensitivity without affecting the specificity of the assays. Likewise, the use of cycloheximide led to an increase in the sensitivity of the serum VT-neutralizing antibody test by a factor of over eightfold.

Animals↗

Rifampin alone or with trimethoprim for contacts of children with Haemophilus influenzae type b infections.

We carried out a nonrandomized, unblinded study to compare the efficacy of rifampin alone with that of rifampin in combination with trimethoprim in the eradication of the Haemophilus influenzae type b (HIB) carrier state among contacts of patients with invasive HIB infection. The study population comprised 17 index patients admitted to hospital with severe HIB infections and 233 contacts, 43 of whom had nasopharyngeal colonization with HIB of the same biotype as that of the index patient. Rifampin in a daily dose of 20 mg/kg (maximum 600 mg) for 4 days eradicated the carrier state in 86% of cases, as did the combination of rifampin at the same dosage and trimethoprim in a daily dose of 5 mg/kg (maximum 160 mg) for 4 days.

Adult↗

Cleaning up pertussis vaccine.

The side effects regularly observed with standard pertussis vaccine are thought to be due to its endotoxin content. Using polymyxin-Sepharose affinity chromatography the endotoxin content of the vaccine can be reduced 1000-fold. Assays are currently in progress to test the protective effect of the purified vaccine.

Chromatography, Affinity↗

Antibiotic susceptibility of blood and cerebrospinal fluid isolates of Haemophilus influenzae.

One hundred and sixty-nine blood and cerebrospinal fluid isolates of Haemophilus influenzae, collected in the Province of Ontario from children and adults from 1976 to 1983, were tested for susceptibility to six conventional and eight newer antibacterial drugs. Most active were ceftriaxone, ceftizoxime and cefotaxime (MIC90 less than or equal to 0.02 mg/l); latamoxef (moxalactam), acrosoxacin and ceftazidime were close behind with MIC90s in the 0.05-0.09 mg/l range. Twenty-five strains (14.8%) were beta-lactamase-producing and thus resistant to ampicillin. There were no chloramphenicol-resistant strains. The isolates showed intermediate but still clinically useful susceptibility to trimethoprim, rifampicin, cefuroxime, piperacillin and chloramphenicol and were least susceptible to gentamicin and sulphamethoxazole.

Adult↗

Sensitive method for detecting low numbers of verotoxin-producing Escherichia coli in mixed cultures by use of colony sweeps and polymyxin extraction of verotoxin.

High titers of Verotoxin (VT) were released from cell pellets of VT-producing Escherichia coli (VTEC; corresponding to E. coli strains producing "high" levels of Shiga-like toxin) after incubation in polymyxin B (0.1 mg/ml) for 30 min at 37 degrees C. Maximal titers of polymyxin-releasable VT occurred in cells obtained from 5-h Penassay broth cultures and were up to eightfold higher than the peak culture supernatant VT titers which occurred in 8-h cultures. Polymyxin-releasable cell extracts of 5-h broth cultures inoculated with mixtures of VT-positive (VT+) and VT-negative strains had easily detectable VT titers when the proportion of VT+ cells in the mixture was about 1.0%, but culture supernatants were negative for VT even when this proportion was 20%. The results were the same whether the initial inoculum consisted of broth culture mixtures of VT+ and VT-negative strains or colony sweeps (loopfuls of confluent bacterial growth) taken from solid plate media previously inoculated with the broth mixtures. In a clinical study, 80 stool cultures from patients with hemolytic uremic syndrome and family contacts with diarrhea were tested for free fecal VT, VT in polymyxin extracts of colony sweeps (VT/PECS), and VTEC (examination of 20 separate E. coli colonies from primary media for VT production). Of the 80 samples, 40 were positive for at least one of these three tests; all 40 were positive for free fecal VT, and 20 of these were positive for VT/PECS. VTEC (as few as 1 colony out of 20) were only isolated from 14 of the 20 cultures that were positive for VT/PECS. In six cases, the VT/PECS was positive even when none of 20 colonies tested were VT+, suggesting that the procedure was able to detect a proportion of VTEC that was less than one in 20(5%). We conclude that the VT/PECS method is highly sensitive for detecting low concentrations of VTEC in stools and provides a rapid method for screening out stools that are negative for VTEC. The technique should also be of value in epidemiological studies for detecting low numbers of VTEC in animal feces, foods, and environmental samples.

Bacterial Toxins↗

Cation and anion transport pathways in volume regulatory response of human lymphocytes to hyposmotic media.

The regulatory volume decrease of osmotically swollen human peripheral blood lymphocytes can be inhibited by agents acting on volume-activated K+- or Cl--transport pathways. Quinine, cetiedil, and 3,3'-dipropylthiadicarbocyanine were found to block the volume-induced K+ transport by interaction with sites on the outside face of the membrane, perhaps by competition with external K+. Drugs known to influence calmodulin action inhibit both volume-induced K+ and Cl- transport to varying degrees. Those inhibitors, particularly of K+ transport, are correlated with their calmodulin-antagonist activity. Penetrating sulfhydryl (SH) reagents (in contrast to nonpenetrating ones) are potent inhibitors of both volume-induced K+ and Cl- movements, indicating the presence of functionally important SH groups located within the membrane or at the cytoplasmic face. A number of agents, such as dipyridamole and oligomycin C, are specific inhibitors of the volume-activated anion pathway. In all respects studied, the inhibition characteristics of the volume-activated K+ pathway of lymphocytes resemble those of the Ca2+-activated K+ channel of red cells. In contrast, the volume-induced anion permeability differs from the primary anion-transport pathway of red cells.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Antibiotic resistance of degraded strains of Bordetella pertussis.

The susceptibilities to erythromycin, rifampin, polymyxin B, ampicillin, tetracycline, gentamicin, fusidic acid, trimethoprim, and spectinomycin of five virulent phase I strains of Bordetella pertussis and their degraded phase IV descendants were compared. Increases in MICs of 2- to 16-fold were observed for erythromycin, rifampin, tetracycline, fusidic acid, trimethoprim, and spectinomycin for four of the five degraded strains.

Anti-Bacterial Agents↗

In vitro interactions between rifampin and ampicillin or chloramphenicol against Haemophilus influenzae.

Twenty clinical isolates of Haemophilus influenzae type b were used to determine the in vitro interactions of rifampin with ampicillin or chloramphenicol. Potential interactions of the drugs were evaluated by calculating the fractional inhibitory concentration index and fractional bactericidal concentration index for each strain after treatments with the drugs alone and in combination. There was no evidence of synergy or antagonisms between ampicillin and rifampin or between chloramphenicol and rifampin. With ampicillin-susceptible H. influenzae type b strains, an additive effect was observed with seven strains, and an indifferent effect was observed with three strains. Similarly, with chloramphenicol-susceptible H. influenzae type b strains, an additive effect was observed with eight strains, and an indifferent effect was observed with two strains.

Ampicillin↗

Susceptibility of Bordetella pertussis to cephalosporin derivatives and imipenem.

The in vitro activities of 16 cephalosporin derivatives and imipenem against 60 strains of Bordetella pertussis were examined. Cefoperazone, imipenem, and ceftriaxone were the most active, with MICs that inhibited 90% of the strains of 0.006, 0.05, and 0.1 microgram/ml, respectively. Cephalexin, cephradine, and cefsulodin were the least active, with MICs of 25 to 125 micrograms/ml. The remainder of the agents demonstrated intermediate activity.

Anti-Bacterial Agents↗