A call for the regulation of prescription data mining.
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Biomedical subjects
Publications and source records attributed to D E Zoutman.
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The authors characterized the in vitro antibacterial properties of clinical doses of lidocaine on isolates of a variety of bacterial pathogens commonly encountered in the setting of nosocomial wound infection (Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus) as well as a number of resistant strains of methicillin-resistant S. aureus and vancomycin-resistant enterococci. Time-kill studies were carried out on bacteria exposed to various clinical concentrations of lidocaine (0%, 1%, 2%, and 4%) with and without epinephrine (1:100,000). Minimum inhibitory concentrations and minimum bactericidal concentrations were determined for some strains using a broth macrodilution method recommended by the National Committee of Clinical Laboratory Standards. Lidocaine demonstrated a dose-dependent inhibition of growth for all strains of bacteria tested. The greatest sensitivity to lidocaine was shown by gram-negative organisms; the least sensitive was S. aureus. The addition of epinephrine to the local anesthetic had no effect on the susceptibility of the bacteria to lidocaine. These observations suggest that the surgical benefit of local anesthesia may extend beyond its analgesic properties and may have a role in the prophylaxis and, in the case of methicillin- and vancomycin-resistant bacteria, the treatment of surgical wound infection, mandating a wider application of this modality.
S-Nitrosothiols occur endogenously and are thought to function as storage forms and/or stable carriers of nitric oxide. Moreover, the S-nitrosothiols have been postulated to function as neurotransmitters and mediate the vasodilator action of glyceryl trinitrate. Because of the increasing pharmacological and physiological interest in S-nitrosothiols, a sensitive method for analysis of these substances is required. We describe a sensitive method based on adsorptive stripping voltammetry for measurement of two S-nitrosothiols, namely, S-nitroso-N-acetyl-D-penicillamine (SNAP) and S-nitrosoglutathione (SNOG), in Krebs' solution. The method is based on the irreversible electrochemical reduction of SNAP and SNOG at the hanging mercury drop electrode (HMDE). The analytes were adsorbed at the HMDE for 60 s at -0.100 V, then exposed to a cathodic linear potential scan of 100 mV s(-10) which resulted in the reduction of SNAP at -0.470 V and SNOG at -0.530 V. Under these conditions, 4 nM SNAP and 11 nM SNOG were readily quantified. Using the above method, we were able to confirm the rapid degradation of SNAP under UV irradiation. Reproducibility of the method as applied to the analysis of these S-nitrosothiols in Krebs' solution was demonstrated by the within-day and day-to-day coefficients of variation of 1.5% and 2.0%, respectively.
In several recent publications on pyocyanine, its mechanism of action has been attributed to an ability to react with nitric oxide (NO), resulting in the formation of an adduct. We examined the chemical interaction of pyocyanine and NO using electrospray (ES) MS, spectrophotometry and voltammetry at neutral pH and with 10-100 microM pyocyanine. No binding of NO to pyocyanine was observed. Alternative mechanisms for the inhibition of NO-induced vasorelaxation by pyocyanine should be sought.
We have developed an adsorptive stripping voltammetric (AdSV) method that can be used for analysis of pyocyanin at the nanomolar level. The method employs a hanging mercury drop electrode (HMDE) as a working electrode in a three-electrode system in a 15-mL quartz cell. Preconcentration of pyocyanin in a 10-mM ammonia buffer (pH 8.0) on the HMDE is carried out by adsorption under conditions of controlled mass transfer for 60 sec, followed by scanning the electrode potential that results in reduction (cathodic scan) or oxidation (anodic scan) of the accumulated pyocyanin. For analysis of pyocyanin in samples containing a significant amount of surface-active species from a bacterial culture broth, a positive-going (anodic) potential scan must be applied after an adsorption at -0.50 V. Anodic scan of the adsorbed pyocyanin provided a well-defined oxidation peak at a potential of -0.17 V. The "anodic scan" variant of the method was tested for utility in Mueller-Hinton broth diluted from 20 to 200 times in a 10-mM ammonia buffer. Reproducibility of the method as applied to the analysis of pyocyanin produced by Pseudomonas aeruginosa (18.83 +/- 0.32 microM) in culture was demonstrated by the within-day and day-to-day coefficients of variation of 1.7% and 3.4%, respectively.
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A 39-year-old male, originally from Antigua, West Indies, presented with a 12-year history of swelling of the left foot. A pathogen could not be recovered in cultures of three surgical biopsy specimens. During follow-up, pus and grains were expressed from a draining sinus tract and Cylindrocarpon destructans grew in pure culture. Retrospective examination of histologic sections of tissue removed during the third biopsy demonstrated a grain characteristic of eumycotic mycetoma. Although the fungus was susceptible to amphotericin B and ketoconazole in vitro, the patient refused treatment, and the clinical course over almost 19 years has been one of slow but progressive bone destruction. The fungus was identified by its microconidial morphology, the presence of chlamydospores, and an intense brown diffusible pigment. It was compared with another poorly known agent of white grain mycetoma, Phialophora cyanescens, characterized by phialidic conidia, chlamydospores in aggregations, and an intense diffusing pigment. The new combination Cylindrocarpon cyanescens (de Vries et al.) Sigler comb. nov. is proposed.
Pseudomonas aeruginosa adheres to respiratory epithelial cells in a highly specific fashion. In order to study the role of P. aeruginosa polar pili in the adherence process we conducted a quantitative morphological electron microscopic examination of P. aeruginosa adherence to SO2 injured canine tracheal cells in vitro. A pilin lacking background strain of P. aeruginosa PAK (BLP2) was constructed using a gene replacement and it in turn was engineered to express either the pilin gene of P. aeruginosa PAO, PAK, or no pilin gene. After 30 minutes incubation of these bacterial strains with injured canine tracheal rings the P. aeruginosa strains expressing pili adhered quantitatively more to the injured tracheal cells than did the pili lacking strains. PAO bearing strains adhered in greater numbers than PAK bearing strains. Healthy tracheal cells did not have any bacteria bound to their surfaces. The bacteria bound to the cilia and lateral edge of the exfoliating tracheal cells. Invasion of tracheal cells by piliated P. aeruginosa bacteria and penetration into the submucosa was also demonstrated. These data confirm the role of pili as important adhesins to injured tracheal cells. The difference in the adherence characteristics of pilin types PAK versus PAO may relate to the differences in the primary structure of these two pilin molecules.
Granulomatous hepatitis is a common cause of fever of unknown origin in up to 13% of patients with prolonged fever. Attempts to define an exact etiology of the granulomatous hepatitis frequently does not yield a precise diagnosis, so that the physician must consider empiric treatment. In this paper we retrospectively review 23 patients in whom granulomatous hepatitis was found as part of the initial assessment of fever of unknown origin, and we report on their outcomes after an overall prospective follow-up of 37 months. In 26% a precise diagnosis was established at the time of assessment: Q-fever in three, mycobacterial disease in two, and histoplasmosis in one. In the remaining 74% no etiology was established after 44 months follow-up. Forty-one percent of the idiopathic group resolved spontaneously without therapy, and 18% received short-term prednisone or indomethacin with a favourable outcome. The remaining 41% required long-term prednisone therapy for a mean of 33.1 months, but all have remained afebrile and otherwise healthy after 59.6 months follow-up. We conclude that patients with fever of unknown origin who are diagnosed as having idiopathic granulomatous hepatitis have an excellent prognosis, even the minority who require long-term corticosteroids.