bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Delirium Index, a Measure of the Severity of Delirium: New Findings on Reliability, Validity, and Responsiveness
Authors: McCusker Jane , Cole Martin G. , Dendukuri Nandini , Belzile Eric 
Published: September 2004

Objectives: To assess the reliability, validity, and responsiveness of an instrument for measuring the severity of delirium, the Delirium Index (DI).Design: Prospective cohort study, with repeated patient assessments at multiple points in the hospital, at 8 weeks after discharge, and at 6 and 12 months after admission.Setting: The medical services of a primary acute‐care hospital.Participants: Medical admissions aged 65 and older: 165 with delirium and dementia, 57 with delirium only, 55 with dementia only, and 41 with neither.Measurements: Severity of delirium symptoms was measured using the DI. Delirium was diagnosed using the Confusion Assessment Method. Other measures included the Mini‐Mental State Examination, Informant Questionnaire on Cognitive Decline in the Elderly, Barthel Index (BI), premorbid instrumental activities of daily living, Charlson Comorbidity Index, Clinical Severity of Illness scale (CSI), and the Acute Physiology Score (APS).Results: The intraclass correlation coefficient of interrater reliability was 0.98. Two measures of fluctuation were significantly higher in patients with delirium than in those without delirium. At baseline, the DI was correlated with the BI, APS, and CSI in delirious patients with (correlation coefficient (r)=−0.43, 0.17, and 0.36, respectively) or without (r=−0.44, 0.39, 0.22, respectively) dementia. At 8 weeks, in delirious patients with and without dementia, internal responsiveness as measured by effect sizes was −0.60 and −0.74, respectively, and the standardized response mean for both groups was −0.64. Low to good levels of external responsiveness were found.Conclusion: The DI appears to be a reliable, valid, and responsive measure of the severity of delirium, in patients with delirium, with or without dementia.
Association Between Subject Functional Status, Seat Height, and Movement Strategy in Sit‐to‐Stand Performance
Authors: Mazzà Claudia , Benvenuti Francesco , Bimbi Carlo , Stanhope Steven J. 
Published: September 2004

Objectives: To explore the association between an individual's functional status, movement task difficulty, and effectiveness of compensatory movement strategies within a sit‐to‐stand (STS) paradigm.Design: Cross‐sectional study.Settings: Rehabilitation unit of the Istituto Nazionale Riposo e Cura Anziani Geriatric Hospital of Florence, Italy.Participants: A convenience sample (131 subjects) of the outpatient clinic and day‐hospital population.Measurements: A performance‐based test (repeated chair standing) was used to divide the subjects into five functional groups. Subjects performed a series of single STS tasks across a range of five descending seat heights. They were instructed to stand without using arms or compensatory strategies. If unable, swinging the arms was allowed, and if the inability persisted, subjects could push with their arms during subsequent attempts. The strategy or inability to stand formed the dependent measures.Results: Subjects within the two highest functional groups could complete the single STS task at all seat heights, with a slight increased use of compensatory strategies at the lowest seat height. The effectiveness of the compensatory strategies decreased rapidly as a function of seat height and functional status. One‐third (35.5%) of the subjects in the middle functional group swung their arms at the lower seat heights. Across the three least functional groups, 11.8%, 30.6%, and 83.3% of the subjects, respectively, were unable to stand at the lowest seat height.Conclusion: The individual's functional status and difficulty of the task influenced the effectiveness of a compensatory strategy to maintain the ability to stand, supporting the idea that disability depends on the interplay between environmental demands and physical ability.
Outcome Predictors of Pneumonia in Elderly Patients: Importance of Functional Assessment
Authors: Torres Olga H. , Muñoz Jose , Ruiz Domingo , Ris Josep , Gich Ignasi , Coma Eva , Gurguí Mercè , Vázquez Guillermo 
Published: September 2004

Objectives: To evaluate the outcome of elderly patients with community‐acquired pneumonia (CAP) seen at an acute‐care hospital, analyzing the importance of CAP severity, functional status, comorbidity, and frailty.Design: Prospective observational study.Setting: Emergency department and geriatric medical day hospital of a university teaching hospital.Participants: Ninety‐nine patients aged 65 and older seen for CAP over a 6‐month recruitment period.Measurements: Clinical data were used to calculate Pneumonia Severity Index (PSI), Barthel Index (BI), Charlson Comorbidity Index, and Hospital Admission Risk Profile (HARP). Patients were then assessed 15 days later to determine functional decline and 30 days and 18 months later for mortality and readmission. Multiple logistic regression was used to analyze outcomes.Results: Functional decline was observed in 23% of the 93 survivors. Within the 30‐day period, case‐fatality rate was 6% and readmission rate 11%; 18‐month rates were 24% and 59%, respectively. Higher BI was a protective factor for 30‐day and 18‐month mortality (odds ratio (OR)=0.96, 95% confidence interval (CI)=0.94–0.98 and OR=0.97, 95% CI=0.95–0.99, respectively; P<.01), and PSI was the only predictor for functional decline (OR=1.03, 95% CI=1.01–1.05; P=.01). Indices did not predict readmission. Analyses were repeated for the 74 inpatients and indicated similar results except for 18‐month mortality, which HARP predicted (OR=1.73; 95% CI=1.16–2.57; P<.01).Conclusion: Functional status was an independent predictor for short‐ and long‐term mortality in hospitalized patients whereas CAP severity predicted functional decline. Severity indices for CAP should possibly thus be adjusted in the elderly population, taking functional status assessment into account.
Telithromycin Treatment of Chronic
Chlamydia pneumoniae
Infection in C57BL/6J mice
Authors: Törmäkangas Liisa , Alakärppä Hannu , Bem David Denise , Leinonen Maija , Saikku Pekka 
Published: September 2004

ABSTRACT

Chronic
Chlamydia pneumoniae
infections have been associated with atherosclerosis, but clear knowledge about how these infections should be treated is lacking. We studied the effect of a new ketolide antibiotic, telithromycin, on chronic
C. pneumoniae
lung infection. Female C57BL/6J mice on a 0.2% cholesterol diet were inoculated intranasally with
C. pneumoniae
either two or three times every fourth week. Telithromycin was given to the mice subcutaneously at 75 mg/kg of body weight once daily for 5 or 10 days, starting at 3 days after the last inoculation. Samples were taken at 4 and 12 weeks after the last inoculation. The presence of
C. pneumoniae
DNA in lung tissue was demonstrated by PCR and the detection of lipid accumulation in the aortic sinus by Oil-Red-O staining.
C. pneumoniae
DNA positivity and inflammatory reactions in the lung tissue of the mice inoculated twice were significantly affected by treatment after both inoculations or only after the second inoculation at 12 weeks. Intimal lipid accumulation in the aortic sinus was also slightly but significantly less abundant in the mice treated after both inoculations compared to the levels in those treated only after the second inoculation for 10 days (geometric means, 823 and 4,324 μm
2
, respectively;
P
= 0.033). No differences between the infected, untreated controls and the group inoculated three times and treated for 5 days were seen. We conclude that telithromycin is effective in preventing the development of chronic
C. pneumoniae
infection and intimal lipid accumulation in C56BL/6J mice when the treatment is given after each inoculation.
Multilayer Polyelectrolyte Films Functionalized by Insertion of Defensin: a New Approach to Protection of Implants from Bacterial Colonization
Authors: Etienne O. , Picart C. , Taddei C. , Haikel Y. , Dimarcq J. L. , Schaaf P. , Voegel J. C. , Ogier J. A. , Egles C. 
Published: September 2004

ABSTRACT

Infection of implanted materials by bacteria constitutes one of the most serious complications following prosthetic surgery. In the present study, we developed a new strategy based on the insertion of an antimicrobial peptide (defensin from
Anopheles gambiae
mosquitoes) into polyelectrolyte multilayer films built by the alternate deposition of polyanions and polycations. Quartz crystal microbalance and streaming potential measurements were used to follow step by step the construction of the multilayer films and embedding of the defensin within the films. Antimicrobial assays were performed with two strains:
Micrococcus luteus
(a gram-positive bacterium) and
Escherichia coli
D22 (a gram-negative bacterium). The inhibition of
E. coli
D22 growth at the surface of defensin-functionalized films was found to be 98% when 10 antimicrobial peptide layers were inserted in the film architecture. Noticeably, the biofunctionalization could be achieved only when positively charged poly(
l
-lysine) was the outermost layer of the film. On the basis of the results of bacterial adhesion experiments observed by confocal or electron microscopy, these observations could result from the close interaction of the bacteria with the positively charged ends of the films, which allows defensin to interact with the bacterial membrane structure. These results open new possibilities for the use of such easily built and functionalized architectures onto any type of implantable biomaterial. The modified surfaces are active against microbial infection and represent a novel means of local host protection.
Pharmacodynamic Functions: a Multiparameter Approach to the Design of Antibiotic Treatment Regimens
Authors: Regoes Roland R. , Wiuff Camilla , Zappala Renata M. , Garner Kim N. , Baquero Fernando , Levin Bruce R. 
Published: September 2004

ABSTRACTThere is a complex quantitative relationship between the concentrations of antibiotics and the growth and death rates of bacteria. Despite this complexity, in most cases only a single pharmacodynamic parameter, the MIC of the drug, is employed for the rational development of antibiotic treatment regimens. In this report, we use a mathematical model based on a Hill function—which we call the pharmacodynamic function and which is related to previously publishedEmaxmodels—to describe the relationship between the bacterial net growth rates and the concentrations of antibiotics of five different classes: ampicillin, ciprofloxacin, tetracycline, streptomycin, and rifampin. UsingEscherichia coliO18:K1:H7, we illustrate how precise estimates of the four parameters of the pharmacodynamic function can be obtained from in vitro time-kill data. We show that, in addition to their respective MICs, these antibiotics differ in the values of the other pharmacodynamic parameters. Using a computer simulation of antibiotic treatment in vivo, we demonstrate that, as a consequence of differences in pharmacodynamic parameters, such as the steepness of the Hill function and the minimum bacterial net growth rate attained at high antibiotic concentrations, there can be profound differences in the microbiological efficacy of antibiotics with identical MICs. We discuss the clinical implications and limitations of these results.
Ketolide Antimicrobial Activity Persists after Disruption of Interactions with Domain II of 23S rRNA
Authors: Novotny Guy W. , Jakobsen Lene , Andersen Niels M. , Poehlsgaard Jacob , Douthwaite Stephen 
Published: September 2004

ABSTRACT

Ketolides are the latest derivatives developed from the macrolide erythromycin to improve antimicrobial activity. All macrolides and ketolides bind to the 50S ribosomal subunit, where they come into contact with adenosine 2058 (A2058) within domain V of the 23S rRNA and block protein synthesis. An additional interaction at nucleotide A752 in the rRNA domain II is made via the synthetic carbamate-alkyl-aryl substituent in the ketolides HMR3647 (telithromycin) and HMR3004, and this interaction contributes to their improved activities. Only a few macrolides, including tylosin, come into contact with domain II of the rRNA and do so via interactions with nucleotides G748 and A752. We have disrupted these macrolide-ketolide interaction sites in the rRNA to assess their relative importance for binding. Base substitutions at A752 were shown to confer low levels of resistance to telithromycin but not to HMR3004, while deletion of A752 confers low levels of resistance to both ketolides. Mutations at position 748 confer no resistance. Substitution of guanine at A2058 gives rise to the MLS
B
(macrolide, lincosamide, and streptogramin B) phenotype, which confers resistance to all the drugs. However, resistance to ketolides was abolished when the mutation at position 2058 was combined with a mutation in domain II of the same rRNA. In contrast, the same dual mutations in rRNAs conferred enhanced resistance to tylosin. Our results show that the domain II interactions of telithromycin and HMR3004 differ from each other and from those of tylosin. The data provide no indication that mutations within domain II, either alone or in combination with an A2058 mutation, can confer significant levels of telithromycin resistance.
Antimicrobial Evaluation of Nocathiacins, a Thiazole Peptide Class of Antibiotics
Authors: Pucci Michael J. , Bronson Joanne J. , Barrett John F. , DenBleyker Kenneth L. , Discotto Linda F. , Fung-Tomc Joan C. , Ueda Yasutsugu 
Published: September 2004

ABSTRACT

Nocathiacins are cyclic thiazolyl peptides with inhibitory activity against gram-positive bacteria. BMS-249524 (nocathiacin I), identified from screening a library of compounds against a multiply antibiotic-resistant
Enterococcus faecium
strain, was used as a lead chemotype to obtain additional structurally related compounds. The MIC assay results of BMS-249524 and two more water-soluble derivatives, BMS-411886 and BMS-461996, revealed potent in vitro activities against a variety of gram-positive pathogens including methicillin-resistant
Staphylococcus aureus
, penicillin-resistant
Streptococcus pneumoniae
, vancomycin intermediate-resistant
S. aureus
, vancomycin-resistant enterococci,
Mycobacterium tuberculosis
and
Mycobacterium avium
. Analysis of killing kinetics revealed that these compounds are bactericidal for
S. aureus
with at least a 3-log
10
reduction of bacterial growth within 6 h of exposure to four times the MICs. Nocathiacin-resistant mutants were characterized by DNA sequence analyses. The mutations mapped to the
rplK
gene encoding the L11 ribosomal protein in the 50S subunit in a region previously shown to be involved in the binding of related thiazolyl peptide antibiotics. These compounds demonstrated potential for further development as a new class of antibacterial agents with activity against key antibiotic-resistant gram-positive bacterial pathogens.
Combinations of Adefovir with Nucleoside Analogs Produce Additive Antiviral Effects against Hepatitis B Virus In Vitro
Authors: Delaney William E. , Yang Huiling , Miller Michael D. , Gibbs Craig S. , Xiong Shelly 
Published: September 2004

ABSTRACTCombination therapies may be required for long-term management of some patients chronically infected with hepatitis B virus (HBV). Adefovir is a nucleotide analog that has similar activity against wild-type and lamivudine-resistant HBV. In contrast to lamivudine, clinical resistance to the prodrug adefovir dipivoxil emerges infrequently. Based on its clinical efficacy and low frequency of resistance, adefovir dipivoxil may form an important component of combination regimens. We therefore investigated the in vitro antiviral efficacy of combinations of adefovir with other nucleoside analogs (lamivudine, entecavir, emtricitabine [FTC],and telbivudine [L-dT]) and the nucleotide analog tenofovir. Using a novel stable cell line that expresses high levels of wild-type HBV, we assayed the antiviral activity of each drug alone and in combination with adefovir. All two-drug combinations resulted in greater antiviral effects than treatments with single agents and could be characterized as additive by the Bliss independence model. Analysis using the Loewe additivity model indicated that adefovir exerted additive antiviral effects when combined with lamivudine, FTC, or L-dT and moderately synergistic effects when combined with entecavir or tenofovir. There was no evidence of cytotoxicity with any of the drugs when used alone or in combination at the tested doses.
In Vitro Activities of 2,4-Diaminoquinazoline and 2,4-Diaminopteridine Derivatives against
Plasmodium falciparum
Authors: Ommeh Sheila , Nduati Eunice , Mberu Eddy , Kokwaro Gilbert , Marsh Kevin , Rosowsky Andre , Nzila Alexis 
Published: September 2004

ABSTRACT

The activities of 28 6-substituted 2,4-diaminoquinazolines, 2,4-diamino-5,6,7,8-tetrahydroquinazolines, and 2,4-diaminopteridines against
Plasmodium falciparum
were tested. The 50% inhibitory concentrations (IC
50
s) of six compounds were <50 nM, and the most potent compound was 2,4-diamino-5-chloro-6-[
N
-(2,5-dimethoxybenzyl)amino]quinazoline (compound 1), with an IC
50
of 9 nM. The activity of compound 1 was potentiated by the dihydropteroate synthase inhibitor dapsone, an indication that these compounds are inhibitors of dihydrofolate reductase. Further studies are warranted to assess the therapeutic potential of this combination in vivo.
Antifungal Therapy of Murine
Aspergillus terreus
Infection
Authors: Graybill John R. , Hernandez Steve , Bocanegra Rosie , Najvar Laura K. 
Published: September 2004

ABSTRACT

Aspergillus terreus
is a species which is being seen increasingly frequently and which is highly resistant to amphotericin B in vitro and clinically. We evaluated amphotericin B, caspofungin, and posaconazole in a murine model of acute invasive aspergillosis. Caspofungin and posaconazole both appeared beneficial and may be reasonable treatment alternatives for infection with
A. terreus
.
Epidemiology and Clinical Features of Bloodstream Infections Caused by AmpC-Type-β-Lactamase-Producing
Klebsiella pneumoniae
Authors: Pai Hyunjoo , Kang Cheol-In , Byeon Jeong-Hum , Lee Ki-Deok , Park Wan Beom , Kim Hong-Bin , Kim Eui-Chong , Oh Myoung-don , Choe Kang-Won 
Published: September 2004

ABSTRACT

Cases of bacteremia caused by AmpC-type-β-lactamase-producing
Klebsiella pneumoniae
isolates were retrospectively studied to determine the epidemiologic features and clinical outcomes of bloodstream infections. Among 389 blood isolates recovered from 1998 to 2002, 65 isolates (16.7%) were found to be extended-spectrum β-lactamase (ESBL) or AmpC β-lactamase producers. The β-lactamases from 61 of the 65 isolates were characterized; 28 of 61 isolates produced AmpC-type enzymes (14 isolates each produced DHA-1 and CMY-1-like enzymes), 32 isolates produced TEM or SHV-related ESBLs, and 1 isolate produced a CTX-M-14-like enzyme. To compare the clinical features and outcomes of bloodstream infections caused by AmpC producers with those caused by TEM- or SHV-related ESBL producers, 27 patients infected with isolates producing AmpC-type enzymes (AmpC group) and 25 patients infected with isolates producing TEM- or SHV-related enzymes (ESBL group) were analyzed. There was no significant difference between the AmpC and the ESBL groups in terms of risk factors. When the initial response was assessed at 72 h after antimicrobial therapy, the treatment failure rate for the AmpC group was 51.9% (14 of 27 patients) and the 7- and 30-day mortality rates were 14.8 and 29.6%, respectively, which were similar to those for the ESBL group. When the mortality rate for the patients who received extended-spectrum cephalosporins as definitive treatment was assessed, all four patients in the DHA-1 group and one of three patients in the CMY-1-like group died. In summary, the prevalence of AmpC enzyme-producing
K. pneumoniae
was high at the Seoul National University Hospital, and the clinical features and outcomes for the patients infected with AmpC-producing organisms were similar to those for the patients infected with TEM- or SHV-related ESBL producers.
AcrAB-TolC Directs Efflux-Mediated Multidrug Resistance in
Salmonella enterica
Serovar Typhimurium DT104
Authors: Baucheron Sylvie , Tyler Shaun , Boyd David , Mulvey Michael R. , Chaslus-Dancla Elisabeth , Cloeckaert Axel 
Published: September 2004

ABSTRACT

Multidrug-resistant
Salmonella enterica
serovar Typhimurium definitive phage type 104 (DT104) strains harbor a genomic island, called
Salmonella
genomic island 1 (SGI1), which contains an antibiotic resistance gene cluster conferring resistance to ampicillin, chloramphenicol, florfenicol, streptomycin, sulfonamides, and tetracyclines. They may be additionally resistant to quinolones. Among the antibiotic resistance genes there are two, i.e.,
floR
and
tet
(G), which code for efflux pumps of the major facilitator superfamily with 12 transmembrane segments that confer resistance to chloramphenicol-florfenicol and the tetracyclines, respectively. In the present study we determined, by constructing
acrB
and
tolC
mutants, the role of the AcrAB-TolC multidrug efflux system in the multidrug resistance of several DT104 strains displaying additional quinolone resistance or not displaying quinolone resistance. This study shows that the quinolone resistance and the decreased fluoroquinolone susceptibilities of the strains are highly dependent on the AcrAB-TolC efflux system and that single mutations in the quinolone resistance-determining region of
gyrA
are of little relevance in mediating this resistance. Overproduction of the AcrAB efflux pump, as determined by Western blotting with an anti-AcrA polyclonal antibody, appeared to be the major mechanism of resistance to quinolones. Moreover, chloramphenicol-florfenicol and tetracycline resistance also appeared to be highly dependent on the presence of AcrAB-TolC, since the introduction of mutations in the respective
acrB
and
tolC
genes resulted in a susceptible or intermediate resistance phenotype, according to clinical MIC breakpoints, despite the presence of the FloR and Tet(G) efflux pumps. Resistance to other antibiotics, ampicillin, streptomycin, and sulfonamides, was not affected in the
acrB
and
tolC
mutants of DT104 strains harboring SGI1. Therefore, AcrAB-TolC appears to direct efflux-mediated resistance to quinolones, chloramphenicol-florfenicol, and tetracyclines in multidrug-resistant
S. enterica
serovar Typhimurium DT104 strains.