bluuebunny/crossref_metadata_2025_split huggingface dataset:
Levofloxacin-Resistant Invasive
Streptococcus pneumoniae
in the United States: Evidence for Clonal Spread and the Impact of Conjugate Pneumococcal Vaccine
Authors: Pletz Mathias W. R. , McGee Lesley , Jorgensen James , Beall Bernard , Facklam Richard R. , Whitney Cynthia G. , Klugman Keith P. 
Published: August 2004

ABSTRACT

The emergence of fluoroquinolone resistance in sterile-site isolates of
Streptococcus pneumoniae
is documented in this study characterizing all invasive levofloxacin-resistant (MIC, ≥8 mg/liter)
S. pneumoniae
isolates (
n
= 50) obtained from the Centers for Disease Control and Prevention Active Bacterial Core Surveillance from 1998 to 2002. Resistance among all isolates increased from 0.1% in 1998 to 0.6% in 2001 (
P
= 0.008) but decreased to 0.4% in 2002, while resistance among vaccine serotypes continued to increase from 0.3% in 1998 to 1.0% in 2002, suggesting that fluoroquinolones continue to exert selective pressure on these vaccine serotypes. Only 22% of resistant isolates were not covered by the conjugate vaccine serogroups. Multilocus sequence typing revealed that 58% of resistant strains were related to five international clones identified by the Pneumococcal Molecular Epidemiology Network, with the Spain
23F
-1 clone being most frequent (16% of all isolates). Thirty-six percent of the isolates were coresistant to penicillin, 44% were coresistant to macrolides, and 28% were multiresistant to penicillin, macrolides, and fluoroquinolones. Fifty percent of the isolates were resistant to any three drug classes. Ninety-four percent of the isolates had multiple mutations in the quinolone resistance-determining regions of the
gyrA
,
gyrB
,
parC
, and
parE
genes. In 16% of the isolates, there was evidence of an active efflux mechanism. An unusual isolate was found that showed only a single
parE
mutation and for which the ciprofloxacin MIC was lower (2 mg/liter) than that of levofloxacin (8 mg/liter). Our results suggest that invasive pneumococcal isolates resistant to levofloxacin in the United States show considerable evidence of multiple resistance and of clonal spread.
Steady-State Plasma and Intrapulmonary Pharmacokinetics and Pharmacodynamics of Cethromycin
Authors: Conte John E. , Golden Jeffrey A. , Kipps Juliana , Zurlinden Elisabeth 
Published: August 2004

ABSTRACTThe objective of this study was to determine the steady-state plasma and intrapulmonary pharmacokinetic parameters of orally administered cethromycin in healthy volunteers. The study design included administering 150 or 300 mg of cethromycin once daily to 25 or 35 healthy adult subjects, respectively, for a total of five doses. Standardized and timed bronchoalveolar lavage (BAL) was performed after the last dose. Blood was obtained for drug assay prior to the first and last dose, at multiple time points following the last dose, and at the time of BAL. Cethromycin was measured in plasma, BAL, and alveolar cell (AC) by using a combined high-performance liquid chromatography-mass spectrometric technique. Plasma, epithelial lining fluid (ELF), and AC pharmacokinetics were derived by noncompartmental methods.Cmax/90% minimum inhibitory concentration (MIC90) ratios, area under the concentration-time curve (AUC)/MIC90ratios, intrapulmonary drug exposure ratios, and percent time above MIC90during the dosing interval (%T> MIC90) were calculated for recently reported respiratory pathogens. The kinetics were nonlinear, i.e., not proportional to dose. In the 150-mg-dose group, theCmax(mean ± standard deviations), AUC0-24, and half-life for plasma were 0.181 ± 0.084 μg/ml, 0.902 ± 0.469 μg · h/ml, and 4.85 ± 1.10 h, respectively; for ELF the values were 0.9 ± 0.2 μg/ml, 11.4 μg · h/ml, and 6.43 h, respectively; for AC the values were 12.7 ± 6.4 μg/ml, 160.8 μg · h/ml, and 10.0 h, respectively. In the 300-mg-dose group, theCmax(mean ± standard deviations), AUC0-24, and half-life for plasma were 0.500 ± 0.168 μg/ml, 3.067 ± 1.205 μg · h/ml, and 4.94 ± 0.66 h, respectively; for ELF the values were 2.7 ± 2.0 μg/ml, 24.15 μg · h/ml, and 5.26 h, respectively; for AC the values were 55.4 ± 38.7 μg/ml, 636.2 μg · h/ml, and 11.6 h, respectively. We concluded that theCmax/MIC90ratios, AUC/MIC90ratios, %T> MIC90values, and extended plasma and intrapulmonary half-lives provide a pharmacokinetic rationale for once-daily administration and are favorable for the treatment of cethromycin-susceptible pulmonary infections.
Terbinafine Resistance Mediated by Salicylate 1-Monooxygenase inAspergillus nidulans
Authors: Graminha Marcia A. S. , Rocha Eleusa M. F. , Prade Rolf A. , Martinez-Rossi Nilce M. 
Published: August 2004

ABSTRACTResistance to antifungal agents is a recurring and growing problem among patients with systemic fungal infections. UV-inducedAspergillus nidulansmutants resistant to terbinafine have been identified, and we report here the characterization of one such gene. A sib-selected, 6.6-kb genomic DNA fragment encodes a salicylate 1-monooxygenase (salA), and a fatty acid synthase subunit (fasC) confers terbinafine resistance upon transformation of a sensitive strain. Subfragments carryingsalAbut notfasCconfer terbinafine resistance.salAis present as a single-copy gene on chromosome VI and encodes a protein of 473 amino acids that is homologous to salicylate 1-monooxygenase, a well-characterized naphthalene-degrading enzyme in bacteria.salAtranscript accumulation analysis showed terbinafine-dependent induction in the wild type and the UV-induced mutant Terb7, as well as overexpression in a strain containing thesalAsubgenomic DNA fragment, probably due to the multicopy effect caused by the transformation event. Additional naphthalene degradation enzyme-coding genes are present in fungal genomes, suggesting that resistance could follow degradation of the naphthalene ring contained in terbinafine.
β-Lactamase-Producing Nontypeable
Haemophilus influenzae
Fails To Protect
Streptococcus pneumoniae
from Amoxicillin during Experimental Acute Otitis Media
Authors: Westman Eva , Lundin Susanne , Hermansson Ann , Melhus Åsa 
Published: August 2004

ABSTRACT

Acute otitis media (AOM) is the most common reason for outpatient antimicrobial therapy. Mixed infections pose a potential problem, since the first-line drug used for the treatment of AOM, amoxicillin, can be neutralized by β-lactamase-producing pathogens of the upper respiratory tract. To study the effects of a 5-day course of amoxicillin on a mixed middle ear infection, rats were challenged with
Streptococcus pneumoniae
alone or in combination with β-lactamase-producing nontypeable
Haemophilus influenzae
. Amoxicillin was introduced at the clinical peak of the infection. Local and systemic changes were monitored by otomicroscopy, bacterial culture, and analysis of histological changes and the expression of the transforming growth factor beta (TGF-β) gene. β-Lactamase-producing
H. influenzae
did not demonstrate an ability to protect
S. pneumoniae
. Amoxicillin eradicated the pneumococci in all treated animals but increased to some degree the ability of
H. influenzae
to persist at the site of infection. Thus, only an insignificant acceleration of the resolution of the AOM caused by a mixture of pathogens was observed during treatment. Moderate to major morphological changes could not be avoided by treatment of the mixed infections, but a slight downregulation of TGF-β expression was observed. In contrast to infections caused by a single pathogen, the mixed infections induced white plaques in the tympanic membrane at a remarkably high frequency independent of treatment. These experimental findings constitute support for further studies of antimicrobial drugs and AOM caused by bacteria with and without mechanisms of antibiotic resistance.
Impact of Nelfinavir Resistance Mutations on In Vitro Phenotype, Fitness, and Replication Capacity of Human Immunodeficiency Virus Type 1 with Subtype B and C Proteases
Authors: Gonzalez Luis M. F. , Brindeiro Rodrigo M. , Aguiar Renato S. , Pereira Helena S. , Abreu Celina M. , Soares Marcelo A. , Tanuri Amilcar 
Published: August 2004

ABSTRACT
Human immunodeficiency virus type 1 subtype B and C proteases were manipulated to contain 90M, 88D, or 89L, and their in vitro biological properties were studied. We showed that D30N has significantly more impact in subtype C than in subtype B counterparts, accounting for the reported low prevalence of this mutation in patients failing nelfinavir-based regimens.
Quinolone-Resistant
Haemophilus influenzae
in a Long-Term-Care Facility: Nucleotide Sequence Characterization of Alterations in the Genes Encoding DNA Gyrase and DNA Topoisomerase IV
Authors: Li Xinying , Mariano Noriel , Rahal James J. , Urban Carl M. , Drlica Karl 
Published: August 2004

ABSTRACT

Fluoroquinolone-resistant isolates of
Haemophilus influenzae,
obtained from a long-term care facility, were examined for nucleotide sequence differences in the quinolone-resistance-determining regions of
gyrA, gyrB, parC
, and
parE
. Similarities among the resistant isolates, plus multiple differences with susceptible isolates, suggest clonal dissemination involving two resistant subclones.
Lack of Association between Hypermutation and Antibiotic Resistance Development inPseudomonas aeruginosaIsolates from Intensive Care Unit Patients
Authors: Gutiérrez Olivia , Juan Carlos , Pérez José L. , Oliver Antonio 
Published: August 2004

ABSTRACTHypermutation is a common feature ofPseudomonas aeruginosaisolates from chronically infected cystic fibrosis patients that is linked with antibiotic resistance development. In this work, using a large collection of sequentialP. aeruginosaisolates from ICU patients, we found that despite the fact that mutational antibiotic resistance development is a frequent outcome, the prevalence of hypermutable strains is low (found in isolates from only 1 of 103 patients) and there is no evidence of coselection of the hypermutable and antibiotic resistance phenotypes.
Genetic and Culture-Based Approaches for Detecting Macrolide Resistance inChlamydia pneumoniae
Authors: Riska Paul F. , Kutlin Andrei , Ajiboye Patrick , Cua Arnold , Roblin Patricia M. , Hammerschlag Margaret R. 
Published: August 2004

ABSTRACTThree clinicalChlamydia pneumoniaeisolates for which the MIC of azithromycin increased after treatment were investigated for genetic evidence of macrolide resistance. Attempts to induce antibiotic resistance in vitro were made. No genetic mechanism was identified for the phenotypic change in theseC. pneumoniaeisolates. No macrolide resistance was obtained in vitro.
Combination Therapy Using Sodium Antimony Gluconate in Stearylamine-Bearing Liposomes against Established and ChronicLeishmania donovaniInfection in BALB/c Mice
Authors: Pal Swati , Ravindran Rajesh , Ali Nahid 
Published: August 2004

ABSTRACTIn this work we report the activity seen with combination therapy using sodium antimony gluconate in liposomes composed of egg phosphatidyl choline and stearylamine for elimination ofLeishmania donovaniparasites from the liver and spleen of BALB/c mice with established and chronic infections.
Activities of Dicationic Compounds against
Trichomonas vaginalis
Authors: Crowell Andrea L. , Stephens Chad E. , Kumar Arvind , Boykin David W. , Secor W. Evan 
Published: August 2004

ABSTRACT

We evaluated 44 novel cationic compounds for activity against metronidazole-sensitive and -resistant
Trichomonas vaginalis
isolates. Six compounds in three different structural classes demonstrated 50% inhibitory concentrations as low as 1 μM against both sensitive and resistant isolates, suggesting a mode of action independent of parasite biochemical pathways that confer resistance to 5-nitroimidazoles.
The AcrAB-TolC Pump Is Involved in Macrolide Resistance but Not in Telithromycin Efflux inEnterobacter aerogenesandEscherichia coli
Authors: Chollet Renaud , Chevalier Jacqueline , Bryskier André , Pagès Jean-Marie 
Published: August 2004

ABSTRACTThe role of the AcrAB-TolC pump in macrolide and ketolide susceptibility inEscherichia coliandEnterobacter aerogeneswas studied. Efflux pump inhibitor restored erythromycin, clarithromycin, and telithromycin susceptibilities to multidrug-resistant isolates. No modification of telithromycin accumulation was detected inE. aerogenes acrABortolCderivatives compared to that in the parental strain. Two independent efflux pumps, inhibited by phenylalanine arginine β-naphthylamide, expel macrolides and telithromycin inE. aerogenes.
OPTIMAL ALLOCATION OF TESTING RESOURCE FOR A MODULAR SOFTWARE
Authors: KAPUR P. K. , JHA P. C. , BARDHAN A. K. 
Published: August 2004

Several Software Reliability Growth Models (SRGMs) have been developed in the literature to account for exponential and S-shaped growth curves. There are others, which can account for both depending on the testing environment. Such models are termed as flexible models. Most of the models use calendar/execution time as the testing time. Very few SRGMs have been developed which define explicitly the testing effort functions into the modeling. Testing effort/resource may be computer time and manpower needed during testing. The aim of this paper is twofold. 1. Develop an SRGM with testing efforts which is also flexible 2. Use model in (1) to allocate optimally the testing resource to a modular software subject to different constraints. Model developed in (1) is validated on different data sets and predictive validity is established. Optimization problems in (2) are mathematical programming problems having the sum of fractional functions as the common objective. These are solved using a dynamic programming approach and closed form solutions have been obtained. Finally, numerical illustrations are provided for two optimization problems.
CHAOTIC BEHAVIOR OF INTERVAL MAPS AND TOTAL VARIATIONS OF ITERATES
Authors: CHEN GOONG , HUANG TINGWEN , HUANG YU 
Published: August 2004

Interval maps reveal precious information about the chaotic behavior of general nonlinear systems. If an interval map f:I→I is chaotic, then its iterates fnwill display heightened oscillatory behavior or profiles as n→∞. This manifestation is quite intuitive and is, here in this paper, studied analytically in terms of the total variations of fnon subintervals. There are four distinctive cases of the growth of total variations of fnas n→∞:(i) the total variations of fnon I remain bounded;(ii) they grow unbounded, but not exponentially with respect to n;(iii) they grow with an exponential rate with respect to n;(iv) they grow unbounded on every subinterval of I.We study in detail these four cases in relations to the well-known notions such as sensitive dependence on initial data, topological entropy, homoclinic orbits, nonwandering sets, etc. This paper is divided into three parts. There are eight main theorems, which show that when the oscillatory profiles of the graphs of fnare more extreme, the more complex is the behavior of the system.
APPLICATION OF MONODISPERSIVE FOAMS AS A SPATIALLY STRUCTURED TWO-PHASE MEDIUM FOR CHEMICAL GAS/LIQUID-REACTIONS
Authors: MATHES HENDRIK , PLATH P. J. 
Published: August 2004

Nonideal mixed yet structured chemical reaction systems tend to exhibit spatial inhomogeneities in their conversion kinetics. Reactive two-phase systems invariably involve coupling phenomena between transport processes and the chemical reaction, at least in the phase boundary region. The spatiotemporal structure of the dispersion determines the contact area as well as contact times, local penetration depths, thus setting the boundary conditions for chemical conversion kinetics and mass transport processes. A monodispersive foam is a system of reduced complexity for investigating spatial and temporal reaction kinetics in conjunction with transport processes. Producing a well-defined foam with equally sized bubbles is a difficult task. After solving this problem, we introduce chemical reactive species into the foams and observe their physicochemical behavior.
EMERGENCIES AS A MANIFESTATION OF THE EFFECT OF BIFURCATION MEMORY IN CONTROLLED UNSTABLE SYSTEMS
Authors: FEIGIN M. I. , KAGAN M. A. 
Published: August 2004

Unusual behavior of dynamic systems with a control parameter is analyzed. Bifurcation induced qualitative changes in phase portraits of such systems are quite routine and ensure efficient operation. This class of systems includes ships with high maneuvering capabilities, aircraft and controlled underwater vehicles designed to be unstable in steady-state motion that are interesting in terms of applications. Bifurcations may generate tracks of bifurcation memory that are "indicators" of regions of reduced controllability referred to as phase spots. The transition process in the phase spot is estimated qualitatively as a universal dependence of the index of loss of controllability on the control parameter. The proposed approach has allowed us to predict and investigate emergency manifestations of the bifurcation memory effect occurring during routine maneuvering.
PERIODICITY AND RECURRENCE IN PIECEWISE ROTATIONS OF EUCLIDEAN SPACES
Authors: MENDES MIGUEL , NICOL MATTHEW 
Published: August 2004

We consider the behavior of piecewise isometries in Euclidean spaces. We show that if n is odd and the system contains no orientation reversing isometries then recurrent orbits with rational coding are not expected. More precisely, a prevalent set of piecewise isometries do not have recurrent points having rational coding. This implies that when all atoms are convex no periodic points exist for almost every piecewise isometry.By contrast, if n≥2 is even then periodic points are stable for almost every piecewise isometry whose set of defining isometries are not orientation reversing. If, in addition, the defining isometries satisfy an incommensurability condition then all unbounded orbits must be irrationally coded.
Combined Therapy of Cilazapril and Losartan Has No Additive Effects in Ameliorating Adriamycin-Induced Glomerulopathy
Authors: Kim Ho-Jung , Ryu Jun-Ho , Han Sang-Woong , Park Ile Kyu , Paik Seung Sam , Park Moon Hyang , Paik Doo Jin , Chung Ho-Sam , Kim Soo Wan , Lee Jong Un 
Published: August 2004

<i>Aims:</i> Effects of the blockade of renin-angiotensin system (RAS), by angiotensin-converting enzyme inhibitor (ACEi), type 1 angiotensin II receptor blocker (ARB), or a combination of both, were evaluated in Adriamycin (ADR)-induced glomerulopathy. <i>Methods:</i> Male Sprague-Dawley rats (180–250 g) were induced of glomerulopathy by treatment with ADR (2 mg/kg, i.v.). Six weeks later, they were treated with cilazapril (1 mg/kg/day) and/or losartan (10 mg/kg/day) for an additional 6 weeks. <i>Results:</i> The urinary excretion of protein progressively increased following the treatment with ADR, which was prevented by ACEi, ARB, and a combination of both. Similarly, the glomerulopathy assessed by glomerulosclerosis index was also ameliorated by ACEi or ARB. However, combined therapy of both ACEi and ARB was without an additional effect (Control 1.4 ± 0.4%, ADR 10.7 ± 2.7%**, ACEi 0.8 ± 0.4%, ARB 2.6 ± 1.0%, ACEi+ARB 1.7 ± 1.5%, ** p < 0.01 vs. Control). The expression of transforming growth factor-β<sub>1</sub> was increased following the treatment with ADR (1.4 ± 0.07-fold, p < 0.05 vs. Control), however, the degree of which was similarly blunted by either ACEi, ARB, or the combination of both. The expression of type 1 angiotensin II receptor mRNA increased following the treatment with ADR, the degree of which was further upregulated by ACEi and decreased by ARB to the control level (ADR 1.3 ± 0.06-fold*, ACEi 1.8 ± 0.05-fold***, ARB 1.0 ± 0.04-fold, * p < 0.05 and *** p < 0.001 vs. Control). The combined therapy of ACEi and ARB still showed an upregulation of type 1 angiotensin II receptor mRNA, however, of which degree was mitigated compared with that induced by ACEi alone (ACEi+ARB 1.5 ± 0.04-fold, ** p < 0.01 vs. Control). On the contrary, the expression of type 2 angiotensin II receptor mRNA was downregulated following the treatment with ADR, which was similarly restored to the control level by ACEi, ARB, and a combination of both (ADR 0.5 ± 0.08-fold**, ACEi 1.0 ± 0.06-fold, ARB 1.0 ± 0.05-fold, ACEi+ARB 1.0 ± 0.05-fold, ** p < 0.01 vs. Control). <i>Conclusion:</i> It is suggested that combined therapy of ACEi and ARB with relatively high or maximal doses of each drug has no additive or synergistic benefits on the progression of ADR-induced glomerulopathy. Effects of RAS blockade may in part be related to differential regulation of type 1 and type 2 angiotensin II receptors.
Do Women Understand the Odds? Risk Perceptions and Recall of Risk Information in Women with a Family History of Breast Cancer
Authors: Hopwood Penelope , Howell Anthony , Lalloo Fiona , Evans Gareth 
Published: August 2004

<i>Objectives:</i> To describe and compare women’s risk perceptions and recall of breast cancer risk information in a cohort of first-time attendees at a family history clinic. <i>Methods:</i> We conducted a 1-year prospective study of 158 women aged 18–45 years with a confirmed lifetime risk of breast cancer of 1 in 6 or greater. Risk perception and recall were assessed using a self-report questionnaire, completed pre-counselling and 3, 6, 9 and 12 months post-counselling, and through interviews conducted at 3 and 12 months. <i>Results:</i> The proportion of women with accurate personal risk perceptions based on ‘gambling’ odds (‘1 chance in x’) significantly improved after risk counselling from 12% pre-counselling to 67% 3 months post-counselling (p < 0.001), which was maintained for 1 year. This was the method of reporting perceived risk associated with the best level of risk accuracy and the women’s preferred format for describing risk, but the concept of lifetime risk was understood by only 44% of women. Qualitative risk categories (‘high’, moderate’ or ‘low’) correlated significantly with women’s self-reported odds values, but each category comprised a wide range of women’s perceived numeric risks. Describing risk as the ‘likelihood of breast cancer’ resulted in a broad and somewhat inaccurate reporting of risk, compared with numeric ratings made at the same time. There was an increase of up to 4-fold in the proportion of women who failed to recall their risk value over time, and women were unable to accurately put the breast cancer risk in context compared with other health threats. <i>Conclusions:</i> All methods of describing risk have limitations, but the results of the present study provide good support for women’s accurate recall of numeric risk values and their preference for use of these ‘gambling’ odds. This may have been influenced by consistency of the use of this method both in risk communication and in personal summary letters. Descriptive risk formats reflected higher levels of perceived vulnerability to breast cancer, and genetic counsellors need to be aware of these different perceptions.