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PubMed1991

Effect of the kappa-receptor agonist, U-50,488H, on cerebral ischemia-induced impairment of working memory assessed in rats by a three-panel runway task.

The effect of U-50,488H, a selective kappa-receptor agonist, on memory functions in an animal model of cerebral ischemia was investigated by use of a three-panel runway task. A 5-min period of ischemia caused a significant increase in the number of errors (pushes made on the two incorrect panels of the three panel-gates at four choice points) in a working memory task but it did not impair a reference memory task. U-50,488H at 10 and 32 mg/kg, administered i.p. immediately after blood flow restoration significantly reduced the increase in errors expected to occur in a working memory task assessed 24 h after 5 min of ischemia. This protective effect of U-50,488H on amnesia in the ischemic rat was antagonized by the kappa-receptor antagonist, MR-2266. We conclude that U-50,488H prevents the impairment of working memory following transient forebrain ischemia, an event mediated by the activation of the kappa-opioid receptor.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1993

Working memory deficits induced by intrahippocampal administration of 8-OH-DPAT, a 5-HT1A receptor agonist, in the rat.

In a test of working memory using a three-panel runway task, the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), at 1.0 mg/kg i.p. significantly increased the number of errors (attempts to pass through two incorrect panels of the three panel gates at four choice points), but it had no effect on errors in a test of reference memory. Intrahippocampal injection of 8-OH-DPAT at 10 micrograms/side also significantly increased the number of working memory errors, without affecting that of reference memory errors. The effect of intrahippocampal 8-OH-DPAT (10 micrograms/side) on working memory was blocked by the 5-HT1A receptor antagonist, (-)-propranolol, at 5 mg/kg i.p. These results suggest that activation of hippocampal 5-HT1A receptors impairs working memory, but does not affect retention of reference memory.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2001

The comparative antigenic characterization of Newcastle disease virus strains isolated in Kenya and Kazakhstan.

Twenty six Newcastle disease viruses--12 reference strains and 14 strains isolated in Kenya and Kazakhstan--were characterized by means of a large panel of 38 monoclonal antibodies (MAB) directed against all the three envelope proteins: matrix, hemagglutinin-neuraminidase and fusion. The essential distinctions were revealed between the viruses isolated in Kenya and Kazakhstan while the differences amongst the viruses belonging to the same local group were much smaller. The heterogeneity amongst the viruses isolated in Kenya was more expressed as compared to the Kazakhstanian strains.

Animals↗

PubMed2001

Evaluation of an automated system for the identification and antimicrobial susceptibility testing of enterococci.

The performance of a new version of an automated system panel, the Positive Combo Panel Type 11 of MicroScan WalkAway 96 (WA96; Dade Behring) was evaluated and compared to that of reference methods for the identification and for antimicrobial susceptibility testing of the different enterococcal species. A total of 376 enterococcal isolates were tested. The MicroScan WA96 correctly identified 99.6% (266/267), 78.3% (18/23) and 68.6% (59/86) of Enterococcus faecalis, Enterococcus faecium and species other than E. faecalis and E. faecium, respectively. Although low probability of accurate identification was obtained for 37 (9.8%) strains, the system indicated that supplementary tests were necessary for precise identification of 8 (9.3%) among the 86 strains included in the non-faecalis/non-faecium group and of 3 (13.0%) among the E. faecium isolates. In comparison to the agar screening method, the percentage of agreement for detection of resistance markers by the automated system was 90.2% (37/41) for ampicillin, 90.6% (48/53) for high-level resistance to streptomycin (HLRS), 96.4% (80/83) for high-level resistance to gentamicin (HLRG), and 100% (14/14) for vancomycin. The results indicate that the MicroScan WA96 performed well for the identification of E. faecalis and typical E. faecium isolates, and for the detection of resistance to vancomycin and HLRG. However, the system still needs further improvement in order to provide reliable results for the characterization of the other enterococcal species, including atypical variants of E. faecium.

Autoanalysis↗

PubMed1998

Clonal dissemination of vancomycin-resistant Enterococci and comparison of susceptibility testing methods.

One hundred fifty clinical isolates of Enterococcus faecalis (88 isolates) and Enterococcus faecium (62 isolates) were tested in vitro for their susceptibility to vancomycin and high-level aminoglycosides (HLA). Remel's Synergy Quad Plates (RSQ) were used as the reference method and compared to Kirby-Bauer disc diffusion test, Vitek GPS-TA card, MicroScan Panel (GP-6), and Etest. Streptomycin susceptibility results for MicroScan GP-6 and RSQ were recorded at 24 and 48 h and all other methods and antibiotics were read at 24 h or less. When compared with the agar screen method, all of the methods demonstrated > 99% agreement. One isolate was falsely sensitive to gentamicin at 24 h, but resistant at 48 h, when tested on both MicroScan and RSQ agar screen. Thirty-nine isolates showed resistance to vancomycin with all methods. These isolates were from three different local hospitals and were identified as E. faecium. Pulse-field gel electrophoresis demonstrated that all of the vancomycin-resistant isolates were derived from the same clone. Of interest is the observation that high-level resistance to aminoglycosides varied between the clonally related isolates.

Aminoglycosides↗

PubMedDate not supplied

The cost-effectiveness of argatroban treatment in heparin-induced thrombocytopenia: the effect of early versus delayed treatment.

A decision-tree analysis was used to estimate the average cost per patient using the direct thrombin inhibitor argatroban for early treatment (<48 hours after thrombocytopenia onset) compared with delayed treatment (> or =48 hours after thrombocytopenia onset) of immune-mediated heparin-induced thrombocytopenia (HIT) with or without thrombosis. Clinical probability data used to populate the model were obtained from argatroban clinical trials and from published clinical literature. Resource utilization data and cost data were also obtained from available literature, the 2003 Physician's Fee Reference, the Healthcare Cost and Utilization Project 2000, the 2003 Drug Topics RedBook, and a modified Delphi panel. The total per-patient cost included hospital days, diagnostic tests, heparin, argatroban, major hemorrhagic events, and patient outcomes (ie, amputation, new thrombosis, stroke, or death), multiplied by the probability of each event. The incremental cost-effectiveness ratio was calculated by dividing the incremental cost between patients with and without argatroban treatment by the incremental effectiveness, or the cost per new thrombosis event avoided. The mean cost per HIT patient without thrombosis who did not receive argatroban was $38,046. The mean cost decreased by 6.85% for patients who were treated earlier with argatroban therapy (average cost, $35,441), representing a $2605 saving per patient compared with those not treated with argatroban. For those receiving delayed argatroban therapy, the mean cost increased by $9024 per patient compared with those receiving early treatment with argatroban. The mean cost for HIT patients with thrombosis who did not receive argatroban was $48,101, which was 9.0% higher than for those receiving early argatroban therapy, representing a $3957 savings per patient. For HIT with thrombosis, mean costs increased by 18.2% in patients whose argatroban was delayed, representing a cost increase of $8020 per patient compared with early treatment (mean cost $44,144 for early treatment and $52,164 for delayed treatment). The results of this analysis support the recommendation to initiate early argatroban treatment upon suspicion of HIT to reduce the thrombotic consequences of HIT and associated healthcare costs. Argatroban therapy should not be delayed pending the results of HIT diagnostic tests.

Arginine↗

PubMed2005

Molecular and phenotypic features for identification of the opportunistic pathogens Ochrobactrum spp.

Among the six species characterized within the genus Ochrobactrum, Ochrobactrum anthropi and Ochrobactrum intermedium are currently reported as opportunistic pathogens in humans. Since the species identification is mainly based on 16S rDNA analysis, the aim of this study was to search for other characteristics useful for Ochrobactrum species discrimination. Ribotyping, morphological and biochemical analyses, and antimicrobial susceptibility testing were performed for a panel of 35 clinical isolates, first identified to the species level using 16S rDNA sequencing. Type and reference strains of five Ochrobactrum species were comparatively analysed. Commercial identification systems such as API 20NE and VITEK 2 were tested for their ability to identify Ochrobactrum anthropi and to detect other members of the genus Ochrobactrum. An improved protocol for the identification of Ochrobactrum spp. by routine medical microbiology practices is proposed: isolation of a non-fastidious non-fermenting oxidase-positive Gram-negative rod resistant to all beta-lactams except imipenem indicates the genus Ochrobactrum, and the API 20NE system confirms the genus identification for most strains, whereas the VITEK 2 system using ID-GNB cards was less powerful. Urease activity, the mucoidy of the colonies, growth at 45 degrees C on tryptic soy agar, and susceptibility to colistin, tobramycin and netilmicin should be considered as differential characteristics for identification of O. anthropi and O. intermedium to the species level. However, definitive identification depends on genotyping methods.

Anti-Bacterial Agents↗

PubMed1980

Evaluation of the Sensititre system for quantitative antimicrobial drug susceptibility testing: a collaborative study.

This three-center collaborative study was conducted to evaluate samples of Sensititre antimicrobial microdilution panels (GIBCO/INVENEX). Sensititre minimum inhibitory concentrations of 27 bacterial isolates were compared with those obtained by a reference microdilution method. The Sensititre and microdilution minimum inhibitory concentrations were equivalent within +/- 1 dilution in 87.6% of the comparable test results. Intralaboratory reproducibilities of the Sensititre and microdilution endpoints were equivalent with 80.4 and 82.4%, respetively, of on-scale endpoints in absolute agreement. Sensititre was more reproducible among laboratories, with nearly a 10% greater agreement of triplicate results. The Sensititre microdilution test as evaluated gave results which were essentially equivalent to those obtained with a standardized microdilution method.

Aminoglycosides↗

PubMed2006

Evaluation of the BD Phoenix automated microbiology system for identification and antimicrobial susceptibility testing of Enterobacteriaceae.

We evaluated the accuracy of the BD Phoenix system for the identification (ID) and antimicrobial susceptibility testing (AST) of 251 isolates of the family Enterobacteriaceae representing 31 species. Organisms were inoculated onto the Phoenix panel according to the manufacturer's instructions. The results from conventional biochemical tests were used for the reference method for ID. Agar dilution, performed according to the CLSI guidelines, was the reference AST method. Essential and categorical agreements were determined. The overall levels of agreement for the genus- and species-level identifications were 95.6% and 94.4%, respectively. Fourteen isolates were incorrectly identified by the Phoenix system; 10 of these were incorrectly identified to the species level. Three of these were Enterobacter (Pantoea) species and four of these were Shigella spp. misidentified as Escherichia coli. For AST results, the essential and categorical agreements were 98.7% and 97.9%, respectively. The very major error, major error, and minor error rates were 0.38%, 0.33%, and 1.8%, respectively. Six isolates (three E. coli isolates and three Klebsiella isolates) were extended-spectrum beta-lactamase producers. All six were flagged by the Phoenix system expert rules. The Phoenix system compares favorably to traditional methods for ID and AST of Enterobacteriaceae.

Anti-Bacterial Agents↗

PubMed1999

Comparison of agar dilution, disk diffusion, MicroScan, and Vitek antimicrobial susceptibility testing methods to broth microdilution for detection of fluoroquinolone-resistant isolates of the family Enterobacteriaceae.

Fluoroquinolone resistance appears to be increasing in many species of bacteria, particularly in those causing nosocomial infections. However, the accuracy of some antimicrobial susceptibility testing methods for detecting fluoroquinolone resistance remains uncertain. Therefore, we compared the accuracy of the results of agar dilution, disk diffusion, MicroScan Walk Away Neg Combo 15 conventional panels, and Vitek GNS-F7 cards to the accuracy of the results of the broth microdilution reference method for detection of ciprofloxacin and ofloxacin resistance in 195 clinical isolates of the family Enterobacteriaceae collected from six U.S. hospitals for a national surveillance project (Project ICARE [Intensive Care Antimicrobial Resistance Epidemiology]). For ciprofloxacin, very major error rates were 0% (disk diffusion and MicroScan), 0.9% (agar dilution), and 2.7% (Vitek), while major error rates ranged from 0% (agar dilution) to 3.7% (MicroScan and Vitek). Minor error rates ranged from 12.3% (agar dilution) to 20.5% (MicroScan). For ofloxacin, no very major errors were observed, and major errors were noted only with MicroScan (3.7% major error rate). Minor error rates ranged from 8.2% (agar dilution) to 18.5% (Vitek). Minor errors for all methods were substantially reduced when results with MICs within +/-1 dilution of the broth microdilution reference MIC were excluded from analysis. However, the high number of minor errors by all test systems remains a concern.

Anti-Infective Agents↗

PubMed2003

The accuracy of the diagnosis of paroxysmal events in children.

OBJECTIVE: To assess the accuracy of the diagnosis of epileptic seizures in children. METHODS: The Dutch Study of Epilepsy in Childhood is a prospective hospital-based study of 881 children referred because of possible seizures. The diagnosis was based on predefined descriptive criteria, as applied by a panel of three pediatric neurologists. Children with a definite other diagnosis were excluded. All children with unclear events were followed up for 1 year and children with seizures were followed up for 2 years to assess the accuracy of the diagnosis. RESULTS: In 170 of 224 children seen after a single event, the incident was classified initially as epileptic, in 54 as unclear. In none of the 170 children did the diagnosis prove to be wrong. In four of the 54 children, recurrent episodes enabled a definite diagnosis of epilepsy. In 412 of the 536 children seen with multiple events, an initial diagnosis of epilepsy was made. After follow-up, this initial diagnosis was probably incorrect in 19. In contrast, seven of 124 children with multiple unclear episodes at intake later received the diagnosis epilepsy. CONCLUSIONS: A false-positive diagnosis of epilepsy was made in 4.6%, whereas a definite diagnosis of epilepsy or seizure was delayed in 5.6% of children with multiple unclear events and in 7.4% of children with one unclear event.

Adolescent↗

PubMed2004

High-impact articles related to the pharmacotherapeutic management of systolic heart failure.

This compilation is part of a series of five articles identifying important literature in cardiovascular pharmacotherapy. This list focuses on pharmacotherapeutic management of acute decompensated and chronic heart failure. Most of the cited works present the results of landmark clinical studies that have shaped the management of patients with left ventricular systolic dysfunction. Limited primary literature is available for some topics; thus, pertinent review articles also are listed. In addition, consensus documents formed by expert panels in the United States and Europe are reviewed. This compilation may serve as a teaching tool, reference resource, or update of the literature for pharmacy clinicians, physicians, and students.

Heart Failure↗

PubMed1990

BK virus terminates tolerance to dsDNA and histone antigens in vivo.

In order to characterize the immune response to BK virus, a human polyomavirus containing dsDNA and host cell histones, we followed the appearance of antibodies in five outbred rabbits after intravenous inoculation with purified infectious BK virus without any adjuvant. The animals were followed for 15 weeks after the first inoculation and booster doses were given after four and eight weeks. Antibodies were studied by ELISA techniques with the BK virus particle, dsDNA, ssDNA or the individual histones as test antigens. Antibodies to BK virus structural proteins were detected in all rabbits. Two out of five rabbits produced antibodies to dsDNA, ssDNA, nucleosomes and histones H1 and H3. Even a weak reactivity to H2B was detected in one serum. The autoantibody response was transient as it declined after a few weeks, but it reappeared after a second boost in one of the rabbits. The other animals did not respond in the same manner. The specificity of the antibodies against dsDNA was ascertained by inhibition studies employing S1 nuclease treated DNA as inhibitor. Furthermore, the dsDNA used as coating antigen was not recognized by a human reference serum with known specificity for ssDNA. The rabbit antisera did not show any reactivity to a panel of other (in this context irrelevant) autoantigens. This suggests that the anti-DNA and -histone antibodies are not a result of non-specific polyclonal B cell activation. Thus, inoculation of dsDNA viruses may represent a new model that allows us to investigate mechanisms responsible for circumvention of tolerance to self molecules.

Animals↗

PubMed1999

HFE genotype in patients with hemochromatosis and other liver diseases.

BACKGROUND: Hereditary hemochromatosis is a common inherited disorder of iron metabolism. The gene HFE, which contains two missense mutations (C282Y and H63D), was recently identified. OBJECTIVE: To determine how HFE genotyping for the C282Y and H63D mutations contributes to the diagnosis of hemochromatosis and to determine the prevalence of HFE mutations in a group of patients with liver disease. DESIGN: Cross-sectional study. SETTING: Academic medical center. PATIENTS: 66 patients with hereditary hemochromatosis and 132 referred patients with other liver diseases. MEASUREMENTS: At initial diagnosis, fasting transferrin saturation, ferritin level, routine chemistry panel, and complete blood count were determined. Percutaneous liver biopsy was done on all patients for histologic analysis and measurement of hepatic iron concentration and hepatic iron index. HFE genotyping for the C282Y and H63D mutations was done on all patients by using genomic DNA samples. RESULTS: Of the 66 patients with hemochromatosis diagnosed on the basis of serum iron studies and liver biopsy findings, 60 (91%) were C282Y homozygotes, 2 (3%) were compound heterozygotes, 1 (1.5%) was a C282Y heterozygote, 2 (3%) were H63D heterozygotes, and 1 (1.5%) was negative for both mutations. Of the 132 patients with liver disease, 6 (5%) were C282Y homozygotes, 8 (6%) were compound heterozygotes, 6 (5%) were C282Y heterozygotes, 5 (4%) were H63D homozygotes, 20 (15%) were H63D heterozygotes, and 87 (66%) were negative for both mutations. All 66 C282Y homozygotes had an elevated hepatic iron concentration, and 65 of the 66 patients (98%) had a transferrin saturation of at least 45%. Ten of the 66 patients (15% [95% CI, 7.5% to 26%]) had a hepatic iron index less than 1.9 mmol/kg per year; hemochromatosis was not suspected in 6 of the 10 patients before genotyping. Cirrhosis or substantial hepatic fibrosis was not seen in any (0% [CI, 0% to 18%]) of the 19 patients younger than 40 years of age who were homozygous for the C282Y mutation. CONCLUSIONS: All 66 patients homozygous for the C282Y mutation of HFE had an elevated hepatic iron concentration, but approximately 15% of these patients did not meet a previous diagnostic criterion for hemochromatosis (hepatic iron index > 1.9 mmol/kg per year). Determination of HFE genotype is clinically useful in patients with liver disease and suspected iron overload and may lead to identification of otherwise unsuspected C282Y homozygotes.

Adult↗

PubMed2006

Vulvovaginal candidiasis from non-albicans species: retrospective study of recurrence rate after fluconazole therapy.

OBJECTIVE: To investigate the recurrence rate of vulvovaginal candidiasis from non-albicans species after fluconazole therapy. STUDY DESIGN: A retrospective cohort of 127 patients with symptomatic vulvovaginal candidiasis by nonalbicans species referred from primary care physicians were evaluated between 1995 and 2004. Complete history, physical examination, basic metabolic panel, and bacterial and fungal cultures were performed. All patients received a daily dose of fluconazole for 30 days. Follow-up evaluations were done at 1, 3, 6, and 12 months. RESULTS: The recurrence rate for all non-albicans vulvovaginitis was 40.2%, 46.5%, 50.4% and 54.2% at 1, 3, 6, and 12 months, respectively. Patients with symptomatic recurrences were more likely to be younger than 35 years of age, older than 65, nulliparous and fastidious vulvar cleaners and were more likely to have concomitant bacterial infections. CONCLUSION: The recurrence rate of symptomatic vulvovaginal candidiasis colonized by non-albicans species after fluconazole therapy was 50.4% at 6 months and 54.2% at 12 months. Nulliparity and age <35 or > 65 years and fastidious vulvar cleaning were positively associated with symptomatic recurrent episodes.

Adult↗

PubMed1997

[Comparison of different phonetic materials for perceptive analysis of dysphonia].

The authors describe a prospective study whose aim was to analyse the influence of the choice of phonetic material on the judgment of the panel. De Krom has already reported an experiment in which perceptive analysis showed that a sustained vowel was a useful material provided that the attack transitory was included (so called complete sustained vowel). He also showed that the panel gave more consistent results with speech or the complete sustained vowel than with the stable part of the sustained vowel. Our first objective was to find out whether we agreed with Krom's results, because for the study in the Dutch language to be applied to the French language, it was necessary to carry out an experimental validation given the cultural differences which might prejudice the results. In additional, we thought it likely that some acoustic information which was present in the attack transitories and was lacking in the stable part of the sustained vowel would run the risk of under-valuing the dysphonia in a study carried out on the stable part of sustained vowels. Our second objective was therefore to demonstrate that in cases of dysphonia, assessment based on the stable part of sustained vowels would be more lenient than those based on speech. The study was carried out using 80 voice samples from 60 dysphonic patients and 20 control subjects. The panel was made up of 7 experienced listeners. Agreement in the jury was judged by the percentage of identical responses given on 3 different presentations of each speech sample. This study showed no differences in the agreement of panel members over the three types of material by changing the severity of classification by the panel was analysed as follows: 1--Pearson r correlation coefficient, comparing on the one hand speech (the reference variable), and on the other samples of the complete vowel and the isolated stable part of the valve (tested variables). 2--A linear regression analysis. Our results confirm that assessments carried out on a sustain/vowel tend to cause a more lenient assessment than those carried out on speech. The assessment carried out on sustained vowels when the attack transient is included were of similar valued to those carried out using speech.

Adult↗

PubMed2005

Official USP Reference Standards: metrology concepts, overview, and scientific issues and opportunities.

The United States Pharmacopeia (USP) is a private standards-setting body created in 1820 by practitioners who wished to promote the quality of therapeutic products in commerce. The principal product of USP, then and now, is the United StatesPharmacopeia (USP), to which was added the National Formulary (NF) in 1975. The two compendia are published as a combined text annually (USP-NF). Originally a book of process standards, USP-NF evolved over time into compendia containing primarily product standards that are expressed in monographs for therapeutic ingredients, products, and excipients. As a public health service, USP supplies official USP Reference Standards to manufacturers and others who wish to test an article according to selected procedures of a monograph or General Chapter. During the past decade, understanding of USP monographs and official USP Reference Standards as a means of controlling the quality of a therapeutic article has evolved, based on advances in metrology, on activities in the International Conference on Harmonization of Technical Requirements for the Registration of Pharmaceuticals for Human Use (ICH), and on considerations by the USP Council of Experts and its Expert Committees and USP staff. This article discusses the evolution of this understanding, focusing on drug substances and excipients for well-characterized small molecules and their corresponding dosage forms.

Adverse Drug Reaction Reporting Systems↗

PubMed1994

A comparative study of serological and biochemical methods for strain differentiation of foot-and-mouth disease type A viruses.

Three serological and three biochemical methods were used to compare five field isolates of foot-and-mouth disease virus (FMDV) from Western India with nine reference vaccine strains and five field isolates from other countries. The serological tests (liquid-phase ELISA and virus neutralization) were able to distinguish between the three reference vaccine strains examined, but the five Indian field isolates reacted poorly with antisera produced against these vaccine strains. Analysis of monoclonal antibody (mAb) data was difficult to interpret although clearly the field isolate A/IND/5/87 reacted to a lesser extent with one of the mAb panels (A10/Holland/42) than the other four Indian isolates. The A22/Iraq/24/64 mAbs did not react with any of the Indian field isolates and only significantly with one of the reference vaccine strains, A/IND/57/79. Polyacrylamide gel electrophoresis distinguished the reference vaccine strains from each other and from the field isolates. Additionally, one of the Indian isolates (A/IND/5/87) could be differentiated from the other four. Electrofocusing showed similarities between the reference vaccine strain A22/Iraq/24/64 and three of the Indian field isolates (A/IND/1/87, A/IND/2/87 and A/IND/3/87), however, A/IND/4/87 and A/IND/5/87 were distinct. Nucleotide sequencing showed that the isolates A/IND/1/87, A/IND/2/87 and A/IND/3/87 were very closely related to each other and related to A/IND/4/87, however, A/IND/5/87 was different.

Amino Acid Sequence↗