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K A Gordon

Publications and source records attributed to K A Gordon.

At least 19 recordsLinked to original sources
PubMed2004

Comparisons of the in vitro susceptibility testing results for garenoxacin using six different national methods: report from the garenoxacin international bridging study.

BACKGROUND: Laboratories worldwide carry out MIC/disc diffusion (DD) tests using various national methods, often published by local organizations. Potentially different results may complicate drug development or registration between the US methods and those used in the European Union (EU). This study uses a new des-F(6)quinolone, garenoxacin, to compare in vitro results among the most utilized antimicrobial susceptibility testing methods. METHODS: Investigators in France, Germany, Spain, Sweden and the UK tested two bacterial collections designated, challenge (CC; n = 330) containing quinolone-resistant strains and national (NC; n = 540) that were recent clinical isolates (2000-2001). Results were compared with values derived from the National Committee for Clinical Laboratory Standards (NCCLS) methods, carried out by the US coordinating site. Discords (greater than four-fold) between MIC method results were repeated. Results were analysed for variation from the NCCLS results (+/-1-2 dilutions or greater than 3-6 mm) and by regression statistics. Ciprofloxacin was used as the control quinolone agent. RESULTS: CC and NC testing compliance averaged 98.4% and 86.4% among participating centres, respectively, and correlation (r) of the national method to the NCCLS MIC was: France (0.98), Germany (0.95), Spain (0.98), Sweden (0.96) and UK (0.95). CC produced MIC results that were identical to the NCCLS (Spain) to 0.6 x log(2) greater (Germany), but the percentage of strains +/-2 dilutions versus NCCLS MIC results was 98% (Germany)-100% (Sweden, UK). Similar patterns were observed for the NC (r = 0.93-0.98), and all nations had >99% of results within +/-2 dilutions (+/-6 mm for disc tests) of NCCLS values. MIC results from four national methods were slightly elevated compared to the NCCLS result (average 0.2 x log(2)). Control ciprofloxacin MIC and DD test results showed similar patterns. CONCLUSIONS: Inter-method garenoxacin susceptibility test results indicate that MIC and zone diameter endpoints derived from five EU methods compare favourably to the NCCLS method results, and generally were identical or a fraction of a log(2) dilution step higher. In contrast, zone diameters for garenoxacin and ciprofloxacin were routinely larger for the EU methods. This unique inter-method 'bridging' experiment allows regulatory agencies to better correlate in vitro testing results derived from procedures that use different national methodologies.

Anti-Bacterial Agents↗
PubMed2002

Comparative antimicrobial spectrum and activity of BMS284756 (T-3811; a desfluoroquinolone) tested against an international collection of staphylococci and enterococci, including in vitro test development and intermethod comparisons.

The study was initiated to determine the in vitro activity and MIC/disk test comparisons of BMS284756, a new des-fluoro(6)-quinolone, against isolates of staphylococci and enterococci from the SENTRY Antimicrobial Surveillance Program, 2000. Isolates were tested by reference broth microdilution and standardized disk diffusion methods. Against 3,789 strains of gram-positive cocci from the SENTRY Program (2000), the BMS284756 MIC90 and percentage susceptible at < or = 2 and < or = 4 microg/ml were: Staphylococcus aureus (4 microg/ml; 89.3 and 97.1%), coagulase-negative staphylococci (CoNS; 4 microg/ml; 86.1 and 96.0%) and enterococci (> 4 microg/ml; 62.0 and 76.2%). Also tested were selected staphylococci (300 strains) and enterococci (102 strains) by two standardized methods. The activity of BMS284756 was highly correlated with oxacillin resistance among staphylococci. Oxacillin-susceptible staphylococci were all inhibited by BMS284756 at < or = 0.5 microg/ml, whereas oxacillin-resistant strains required inhibitory concentrations of > or = 1 microg/ml. Excellent correlation was observed between the MIC and 5-microg disk zone diameter for staphylococci and enterococci (r=0.91 to 0.93). Among vancomycin-susceptible enterococci, 67% of Enterococcus faecalis, 25% of E. faecium, and 76% of other Enterococcus spp. isolates were inhibited by BMS284756 at < or = 2 microg/ml. All vancomycin-resistant enterococci (VRE; 11 E. faecalis and 15 E. faecium) were inhibited by > or = 2 microg/ml of BMS284756. Among the non-VRE, non-faecium enterococcal isolates (n=64), 62% were inhibited by < or = 0.5 microg/ml. BMS284756 showed excellent activity against oxacillin-susceptible staphylococci and moderate activity against enterococci other than VRE and E. faecium. Acceptable correlations were observed between MIC and disk test results for both tested genus groups.

Anti-Infective Agents↗
PubMed2001

Antimicrobial susceptibility testing of clinical isolates of Bordetella pertussis from northern California: report from the SENTRY Antimicrobial Surveillance Program.

Reports of an increased clinical incidence of pertussis and the development of resistance by Bordetella pertussis to erythromycin prompted the collection and testing of recent clinical isolates from patients in northern California against a range of antimicrobial agents by the Etest (AB BIODISK, Solna, Sweden) method. All isolates were fully susceptible to all eight agents tested (MIC, <or=0.38 microg/ml), including newer fluoroquinolones, such as gatifloxacin (MIC of which 90% of the isolates tested are inhibited, 0.006 microg/ml), which may be used in cases of adolescent or adult pertussis. Continued surveillance of B. pertussis isolates appears to be a prudent practice.

Adolescent↗
PubMed2001

Effect of residual hearing prior to cochlear implantation on speech perception in children.

We examined the impact of residual hearing prior to cochlear implantation on pre- and postimplantation speech perception outcomes in children. Stimulation of the auditory system prior to implantation because of the presence of residual hearing is important for development of the central auditory pathways, whereas, in the absence of such stimulation, the pathways show less development. We hypothesized that children who had some degree of residual hearing preimplantation achieve better speech perception skills than their peers with poorer hearing. From the 133 children followed in our program, we identified 37 children who had an audiometric pure-tone average of better than 95 dB HL in the better ear at any time preimplantation. Psychophysical speech perception measures, the Word Identification Picture Inventory and the Phonetically Balanced Kindergarten list, in these children were compared with those of 96 implanted children who had poorer hearing prior to implantation. Children with more residual hearing showed higher speech perception scores both before implantation and over their first year of implant use than children with poorer hearing, suggesting that there is an advantage in having a greater degree of residual hearing preimplantation. We suggest that this advantage is promoted, in part, by the greater potential for auditory stimulation provided by high-gain hearing aids in children with greater degrees of residual hearing. This advantage appears to be maintained at least over 1 year postimplantation, yet the rates of development of postimplantation speech perception are not different between the groups. We suggest that this may be due to the unique aspects of electrical stimulation from a cochlear implant. Our findings suggest that it is important to minimize the delay of speech perception skills in the preimplantation phase, particularly in children with poor residual hearing. This can be accomplished by implanting children with congenital severe to profound hearing loss at young ages and children with acquired hearing loss soon after the onset. Also, auditory stimulation prior to implantation should be maximized through the consistent use of hearing aids and therapy that emphasizes development of auditory skills.

Child↗
PubMed2000

Factors contributing to limited open-set speech perception in children who use a cochlear implant.

Cochlear implants have enabled many children with severe to profound sensorineural hearing loss to develop speech perception skills. However, some children experience few gains while others develop high levels of speech perception. We identified potential factors contributing to poor performance with an implant by studying implanted children who do not develop functional speech perception. Five children were identified as developing no open-set word recognition skills after at least 2 years of implant use. This study group was compared to a randomly selected control group (n=10) and an age-matched control group (n=5). Pre-implant factors were examined using a Graded Profile Analysis and post-implant factors were assessed in a retrospective chart review. A greater number of pre-implant concerns were raised in the study group than in randomized controls (P<0.01). Chronological age and duration of deafness were pre-implant concerns in all study group subjects. A greater number of post-implant concerns were found in the study group than in randomly selected controls (P<0.005). We conclude that while appropriate selection of candidates for cochlear implantation is important in predicting speech perception outcomes, post-implant follow-up is also essential and must include regular monitoring of equipment, monitoring of stimulation levels with use of objective measures of stimulation levels if necessary, and consistent habilitation.

Adolescent↗
PubMed2000

Occurrence of single-point gyrA mutations among ciprofloxacin-susceptible Escherichia coli isolates causing urinary tract infections in Latin America.

To detect if isolates susceptible to quinolones already carry mutations in the gyrA and parC genes, we selected 12 ciprofloxacin-susceptible Escherichia coli strains collected from patients with urinary tract infections in Latin America in 1998, as part of ongoing SENTRY Antimicrobial Surveillance Program. The isolates studied exhibited minimal inhibitory concentrations (MICs) for ciprofloxacin between < or = 0.015 microg/mL and 0.5 microg/mL. The molecular characterization of quinolone resistance was determinated by amplification of the gyrA and parC by PCR followed by sequencing of the respective amplicons. We observed that E. coli isolates exhibiting MIC, < or = 0.06 microg/mL for ciprofloxacin did not show mutations in either topoisomerase. On the other hand, all isolates with MIC between 0.12 microg/mL and 0.5 microg/mL demonstrated single mutation in the gyrA gene. The most frequent mutation occurred at position 83, where the amino acid serine was replaced by leucine. No mutations in the parC gene were observed. To preserve the potency and prevent the development of resistance, we suggest that quinolone usage should be rational, especially in the treatment of urinary tract infections, and in the prophylaxis of immunosupressed patient populations.

Anti-Infective Agents↗
PubMed2000

Two-year assessment of the pathogen frequency and antimicrobial resistance patterns among organisms isolated from skin and soft tissue infections in Latin American hospitals: results from the SENTRY antimicrobial surveillance program, 1997-98. SENTRY Study Group.

OBJECTIVES: This study was conducted to evaluate the frequency of occurrence and antimicrobial susceptibility of bacterial isolates collected from patients with skin and soft tissue infections (SSTI) in Latin American hospitals, as part of the SENTRY Antimicrobial Surveillance Program. The dissemination of multidrug-resistant methicillin-resistant Staphylococcus aureus (MDR-MRSA) among the Latin American countries also was studied. MATERIAL AND METHODS: A total of 885 bacterial isolates were analyzed. At the monitoring laboratory, antimicrobial susceptibility testing utilizing the reference broth microdilution method and confirmation of species identification were performed. Enterobacteriaceae possibly producing extended-spectrum beta-lactamases (ESBL) and MDR-MRSA isolates were genotyped by ribotyping using the RiboPrinter and by pulsed-field gel electrophoresis. RESULTS: Staphylococcus aureus (31%) was the most common etiologic agent causing SSTI, followed by Escherichia coli (13.4%) and Pseudomonas aeruginosa (11%). Thirty-one percent of S. aureus isolates were resistant to oxacillin (methicillin). The presence of ESBL phenotypes was markedly higher among the Klebsiella pneumoniae (35.5%) than E. coli isolates (10. 2%). Meropenem was the compound with the highest susceptibility rate among the Enterobacteriaceae (100%) and P. aeruginosa (95%) isolates. A great genetic similarity was observed among the MDR-MRSA in Latin America. CONCLUSION: High resistance rates to antimicrobial drugs among the most frequent bacterial pathogens were observed in 10 medical centers in Latin America. This study also demonstrated a clonal dissemination of a MDR-MRSA strain in several nations.

Anti-Bacterial Agents↗
PubMed2000

Activity and spectrum of 22 antimicrobial agents tested against urinary tract infection pathogens in hospitalized patients in Latin America: report from the second year of the SENTRY antimicrobial surveillance program (1998).

The potency and spectrum of various antimicrobial agents tested against 434 bacterial isolates causing urinary tract infection (UTI) in hospitalized patients in Latin America were evaluated. The genotypes of the extended-spectrum beta-lactamase-producing and selected multi-resistant isolates were also evaluated by molecular typing techniques. Escherichia coli (60.4%) was the most common aetiological agent causing UTI, followed by Klebsiella spp. (11.2%) and Pseudomonas aeruginosa (8.3%). In contrast, Enterococcus spp. isolates caused only 2.3% of UTIs. Fewer than 50% of E. coli isolates were susceptible to broad-spectrum penicillins. The resistance rates to ciprofloxacin and the new quinolones were also high among these isolates. The molecular characterization of ciprofloxacin-resistant E. coli showed that most of them have a double mutation in the gyrA gene associated with a single mutation in the parC gene. The Klebsiella pneumoniae isolates studied demonstrated high resistance rates to beta-lactam drugs, including broad-spectrum cephalosporins. The carbapenems were the compounds with the highest susceptibility rate among these isolates (100.0% susceptible) followed by cefepime (91.7% susceptible). Meropenem, imipenem and cefepime were also the most active drugs against Enterobacter spp. Among P. aeruginosa isolates, meropenem (MIC(50), 2 mg/L) was the most active compound, followed by imipenem (MIC(50), 4 mg/L), cefepime (MIC(50), 8 mg/L) and ceftazidime (MIC(50), 16 mg/L). The results presented in this report confirm that bacterial resistance continues to be a great problem in Latin American medical institutions.

Anti-Bacterial Agents↗
PubMed1999

The role of a graded profile analysis in determining candidacy and outcome for cochlear implantation in children.

Assessment of candidacy for cochlear implantation in children continues to present a challenge to cochlear implant programs. The efficacy of implantation depends on a number of factors and as a result a multidisciplinary approach has been adopted. At the Cochlear Implant Program at The Hospital for Sick Children, Toronto, we use a graded profile analysis (GPA) which has been adapted from the Children's Implant Profile (CHIP) developed by Hellman (S.A. Hellman, P.M. Chute, R.E. Kretschmer, M.E., Nevins, S.C. Parisier, L.C. Thurston, The development of a Children's Implant Profile, Am. Ann. Deaf. 136 (1991) 77-81). This structured assessment allows each potential candidate to be 'scored' in each category of assessment giving a potential range of -14 to +14. In this retrospective study of 109 candidates we examine the relationship between GPA scores and decision to implant. For those patients who were implanted, the relationship between GPA score and speech perception outcomes was also evaluated. Three distinct groups of children emerged from the analysis. The first group had scores less than 5 and were not considered to be suitable for implantation. Within the second group who scored between 5 and 8, there was no clear relationship between decision to implant and score. The last group, who scored 9-14, was considered to be generally suitable for implantation provided that there were no medical contraindications and the parents consented to implantation. There was a significant association between rate of improvement of speech perception and GPA score. Those patients with scores of 9 to +14 improved at a faster rate than group 5-8 (P < 0.05). The implications of these findings are discussed.

Adolescent↗
PubMed1999

Acute high dose arteether toxicity in rats.

Acute high dose administration of the artemisinin antimalarial, beta-arteether (AE), was evaluated in rats using an auditory discrimination task (ADT) and histology. After rats were trained on the ADT, AE (25, 75, 125 mg/kg, i.m.) or vehicle (sesame oil) was administered and behavioral performance was evaluated for 11 consecutive days. Histological evaluation of the brains was performed using thionine and cupric-silver staining. Damaged cells were counted in specific brainstem nuclei of all rats and a qualitative analysis of the rostral-caudal extent of selected brains was performed. Behavioral performance was not significantly affected by any treatment although some evidence of disruption was observed, particularly after the largest dose. At 125 mg/kg, AE produced statistically significant neuropathology, including chromatolysis, in the nucleus trapezoideus and nucleus superior olive. AE at 75 mg/kg, produced significant neuropathology in the nucleus trapezoideus. Neither AE at 25 mg/kg, nor vehicle produced damage. Qualitative analysis revealed a pattern of neuropathology focused in the brainstem. The results show that, in rats, a single dose of AE can produce a pattern of brainstem neuropathology and that specific brainstem nuclei, including auditory nuclei, are particularly vulnerable. These results are consistent with, and extend, previous studies demonstrating brainstem neurotoxicity from repeated AE administration. Moreover, early detection of AE-induced neuropathology is problematic and may require selective examination of brainstem functions.

Acoustic Stimulation↗
PubMed1998

Synthesis and immunosuppressive activity of ruthenium complexes.

The syntheses and immunosuppressive activity of ruthenium complexes are described. One of the complexes (1a) was shown to be a potent inhibitor of human T-lymphocyte proliferation with an IC50 of 5 nM. The activity of these complexes compares favorably to the well known immunosuppressants Cyclosporin A and Rapamycin.

Cell Division↗
PubMed1995

College health in the national blueprint for a healthy campus 2000.

Beginning in 1985, an ACHA task force studied national health objectives to determine how well colleges and universities were achieving nationally defined health goals. The task force found that the college-aged population was not specifically recognized as a concern among health planners and that little consistent data on the health status of students existed. The task force worked closely with federal agencies in identifying relevant issues and focusing on the higher education community's commitment to disease promotion and positive health behaviors.

Adolescent↗
PubMed1993

An organizational model for developing multidisciplinary clinical research in the academic medical center.

OBJECTIVE: To assess the impact of a new organizational model designed to stimulate multidisciplinary clinical research. METHODS: We conducted a prospective, 3 1/2-year followup of a research training program for residents, fellows, faculty, nurses, and allied health professionals in rheumatology and orthopedic surgery. Program components included a multidisciplinary clinical research conference, a clinical research methods curriculum, consultations, a patient registry, and regular meetings of a Research Methodology Core group. Measures included participation in each program component and the number of new investigators who developed funded clinical research projects. RESULTS: The multidisciplinary clinical research conference was attended by 369 new health professionals; 218 professionals participated in at least one of the courses; and 280 consultations were provided to 108 professionals. Thirteen new investigators developed 17 new grant proposals, of which 14 were externally funded. Investigators who successfully procured funding for new projects demonstrated significantly more participation in program components compared with those who did not (P < 0.001 overall). CONCLUSION: Participation in the program was significantly correlated with the development of new prospective patient-based studies. We conclude that our model has the potential to foster such research in other settings.

Academic Medical Centers↗
PubMed1988

Acidic fibroblast growth factor stimulates adrenal chromaffin cells to proliferate and to extend neurites, but is not a long-term survival factor.

Acidic fibroblast growth factor (aFGF) is a heparin-binding polypeptide that is a mitogen for endothelial cells and glial cells, as well as a differentiation factor for PC12 cells and certain neurons. We show here that aFGF is as potent as nerve growth factor (NGF) in stimulating both neuritic outgrowth and proliferation in adrenal chromaffin cells from young rats, but it fails to support long-term survival. Heparin strongly potentiates aFGF-dependent neuritic outgrowth but not aFGF-dependent proliferation. As is the case with NGF, phorbol myristate acetate depresses aFGF-induced cell division and increases the outgrowth of neurites. On the other hand, dexamethasone antagonizes neuritic outgrowth elicited by both NGF and aFGF but inhibits only proliferation induced by NGF. The effects of basic FGF (bFGF) are similar but not identical to those of aFGF. Thus the regulatory pathways controlled by aFGF, bFGF, and NGF are partially distinct.

Adrenal Medulla↗