bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized, Double-Blind, Placebo-Controlled Trial of Cephalexin for Treatment of Uncomplicated Skin Abscesses in a Population at Risk for Community-Acquired Methicillin-Resistant
Staphylococcus aureus
Infection
Authors: Rajendran Priya M. , Young David , Maurer Toby , Chambers Henry , Perdreau-Remington Francoise , Ro Peter , Harris Hobart 
Published: September 2007

ABSTRACT

Empirical use of beta-lactam antibiotics, the preferred agents for treating uncomplicated skin and soft tissue infections, may no longer be appropriate for these infections because of the increasing prevalence of community strains of methicillin-resistant
Staphylococcus aureus
(MRSA). Retrospective studies, however, suggest that outcomes are good even when beta-lactams are used. We conducted a randomized, double-blind trial of 166 outpatient subjects comparing placebo to cephalexin at 500 mg orally four times for 7 days after incision and drainage of skin and soft tissue abscesses. The primary outcome was clinical cure or failure 7 days after incision and drainage.
S. aureus
was isolated from 70.4% of abscess cultures. Of the isolates tested 87.8% were MRSA, 93% of which were positive for Panton-Valentine leucocidin genes. Clinical cure rates were 90.5% (95% confidence interval, 0.82 to 0.96) in the 84 placebo recipients and 84.1% (95% confidence interval, 0.74 to 0.91) in the 82 cephalexin recipients (difference in the two proportions, 0.0006; 95% confidence interval, −0.0461 to 0.0472;
P
= 0.25). The 90.5% cure rate observed in the placebo arm and 84.1% cure rate observed in the cephalexin arm provide strong evidence that antibiotics may be unnecessary after surgical drainage of uncomplicated skin and soft tissue abscesses caused by community strains of MRSA.
Tn
6001
, a Transposon-Like Element Containing the
bla
VIM-3
-Harboring Integron In450
Authors: Tseng Sung-Pin , Hsueh Po-Ren , Tsai Jui-Chang , Teng Lee-Jene 
Published: September 2007

ABSTRACT

We describe the structure of a transposon-like element named Tn
6001
, which contains a
bla
VIM-3
-harboring integron In450, which was derived from a multidrug-resistant
Pseudomonas aeruginosa
clinical isolate in Taiwan. The transposon backbone structure is most closely related to those of Tn
1404
* and Tn
1403
. Tn
6001
was inserted into the chromosome of the clinical isolate.
Antibiotic Resistance and Single-Nucleotide Polymorphism Cluster Grouping Type in a Multinational Sample of Resistant
Mycobacterium tuberculosis
Isolates
Authors: Brimacombe M. , Hazbon M. , Motiwala A. S. , Alland D. 
Published: September 2007

ABSTRACT

A single-nucleotide polymorphism-based cluster grouping (SCG) classification system for
Mycobacterium tuberculosis
was used to examine antibiotic resistance type and resistance mutations in relationship to specific evolutionary lineages. Drug resistance and resistance mutations were seen across all SCGs. SCG-2 had higher proportions of
katG
codon 315 mutations and resistance to four drugs.
Design, Synthesis, and Evaluation of 10-N-Substituted Acridones as Novel Chemosensitizers inPlasmodium falciparum
Authors: Kelly Jane X. , Smilkstein Martin J. , Cooper Roland A. , Lane Kristin D. , Johnson Robert A. , Janowsky Aaron , Dodean Rozalia A. , Hinrichs David J. , Winter Rolf , Riscoe Michael 
Published: September 2007

ABSTRACTA series of novel 10-N-substituted acridones, bearing alkyl side chains with tertiary amine groups at the terminal position, were designed, synthesized, and evaluated for the ability to enhance the potency of quinoline drugs against multidrug-resistant (MDR)Plasmodium falciparummalaria parasites. A number of acridone derivatives, with side chains bridged three or more carbon atoms apart between the ring nitrogen and terminal nitrogen, demonstrated chloroquine (CQ)-chemosensitizing activity against the MDR strain ofP. falciparum(Dd2). Isobologram analysis revealed that selected candidates demonstrated significant synergy with CQ in the CQ-resistant (CQR) parasite Dd2 but only additive (or indifferent) interaction in the CQ-sensitive (CQS) D6. These acridone derivatives also enhanced the sensitivity of other quinoline antimalarials, such as desethylchloroquine (DCQ) and quinine (QN), in Dd2. The patterns of chemosensitizing effects of selected acridones on CQ and QN were similar to those of verapamil against various parasite lines with mutations encoding amino acid 76 of theP. falciparumCQ resistance transporter (PfCRT). Unlike other known chemosensitizers with recognized psychotropic effects (e.g., desipramine, imipramine, and chlorpheniramine), these novel acridone derivatives exhibited no demonstrable effect on the uptake or binding of important biogenic amine neurotransmitters. The combined results indicate that 10-N-substituted acridones present novel pharmacophores for the development of chemosensitizers againstP. falciparum.
Global Phenotype Screening and Transcript Analysis Outlines the Inhibitory Mode(s) of Action of Two Amphibian-Derived, α-Helical, Cationic Peptides on
Saccharomyces cerevisiae
Authors: Morton C. Oliver , Hayes Andrew , Wilson Michael , Rash Bharat M. , Oliver Stephen G. , Coote Peter 
Published: September 2007

ABSTRACT

Dermaseptin S3(1-16) [DsS3(1-16)] and magainin 2 (Mag 2) are two unrelated, amphibian-derived cationic peptides that adopt an α-helical structure within microbial membranes and have been proposed to kill target organisms via membrane disruption. Using a combination of global deletion mutant library phenotypic screening, expression profiling, and physical techniques, we have carried out a comprehensive in vitro analysis of the inhibitory action of these two peptides on the model fungus
Saccharomyces cerevisiae
. Gene ontology profiling (of biological processes) was used to identify both common and unique effects of each peptide. Resistance to both peptides was conferred by genes involved in telomere maintenance, chromosome organization, and double-strand break repair, implicating a common inhibitory action of DNA damage. Crucially, each peptide also required unique genes for maintaining resistance; for example, DsS3(1-16) required genes involved in protein targeting to the vacuole, and Mag 2 required genes involved in DNA-dependent DNA replication and DNA repair. Thus, DsS3(1-16) and Mag 2 have both common and unique antifungal actions that are not simply due to membrane disruption. Physical techniques revealed that both peptides interacted with DNA in vitro but in subtly different ways, and this observation was supported by the functional genomics experiments that provided evidence that both peptides also interfered with DNA integrity differently in vivo. This implies that both peptides are able to pass through the cytoplasmic membrane of yeast cells and damage DNA, an inhibitory action that has not been previously attributed to either of these peptides.
Interaction Study of the Combined Use of Paroxetine and Fosamprenavir-Ritonavir in Healthy Subjects
Authors: van der Lee Manon J. , Blenke Audrey A. M. , Rongen Gerard A. , Verwey-van Wissen Corrien P. W. G. M. , Koopmans Peter P. , Pharo Cristina , Burger David M. 
Published: September 2007

ABSTRACT

Human immunodeficiency virus-infected patients have an increased risk for depression. Despite the high potential for drug-drug interactions, limited data on the combined use of antidepressants and antiretrovirals are available. Theoretically, ritonavir-boosted protease inhibitors may inhibit CYP2D6-mediated metabolism of paroxetine. We wanted to determine the effect of fosamprenavir-ritonavir on paroxetine pharmacokinetics and vice versa and to evaluate the safety of the combination. Group A started with 20 mg paroxetine every day for 10 days; after a wash-out period of 16 days, subjects received paroxetine (20 mg every day) plus fosamprenavir-ritonavir (700/100 mg twice a day) from days 28 to 37. Group B received the regimens in reverse order. On days 10 and 37, pharmacokinetic curves were recorded. Twenty-six healthy subjects (18 females, 8 males) were included. Median (range) age and weight were 44.4 (18.2 to 64.3) years and 68.8 (51.0 to 89.4) kg. Three subjects were excluded (two because of adverse events; one for nonadherence). Addition of fosamprenavir-ritonavir to paroxetine resulted in a significant decrease in paroxetine exposure: the geometric mean ratios (90% confidence intervals) of paroxetine plus fosamprenavir-ritonavir to paroxetine alone were 0.45 (0.41 to 0.49) for the area under the concentration-time curve from 0 to 24 h (AUC
0-24
), 0.49 (0.45 to 0.53) for the maximum concentration of the drug in plasma (
C
max
), and 0.75 (0.71 to 0.80) for the apparent elimination half-life (
t
1/2
). The free fraction of paroxetine showed a median (interquartile range) increase of 30% (18 to 42%) after the addition of fosamprenavir-ritonavir. The AUC
0-12
,
C
max
,
C
min
, and
t
1/2
of amprenavir and ritonavir were similar to those of historical controls. No serious adverse events occurred. Fosamprenavir-ritonavir reduced total paroxetine exposure by 55%. This is partly explained by protein displacement of paroxetine. We think that this interaction is clinically relevant and that titration to a higher dose of paroxetine may be necessary to accomplish the needed antidepressant effect.
Molecular Epidemiology of Clinical Isolates of Carbapenem-Resistant
Acinetobacter
spp. from Chinese Hospitals
Authors: Wang Hui , Guo Ping , Sun Hongli , Wang He , Yang Qiwen , Chen Minjun , Xu Yingchun , Zhu Yuanjue 
Published: September 2007

ABSTRACT

Carbapenem resistance in
Acinetobacter
spp. is an emerging problem in China. We investigated the molecular epidemiology and carbapenemase genes of 221 nonrepetitive imipenem-resistant clinical isolates of
Acinetobacter
spp. collected from 1999 to 2005 at 11 teaching hospitals in China. Genotyping by pulsed-field gel electrophoresis (PFGE) found 15 PFGE patterns. Of these, one (clone P) was identified at four hospitals in Beijing and another (clone A) at four geographically disparate cities. Most imipenem-resistant isolates exhibited high-level resistance to all β-lactams and were only susceptible to colistin.
bla
OXA-23
-like genes were found in 97.7% of isolates. Sequencing performed on 60 representative isolates confirmed the presence of the
bla
OXA-23
carbapenemase gene. Analysis of the genetic context of
bla
OXA-23
showed the presence of IS
Aba1
upstream of
bla
OXA-23
. All of the 187
A. baumannii
isolates identified by amplified RNA gene restriction analysis carried a
bla
OXA-51
-like oxacillinase gene, while this gene was absent from isolates of other species. Sequencing indicated the presence of
bla
OXA-66
for 18 representative isolates. Seven isolates of one clone (clone T) carried the plasmid-mediated
bla
OXA-58
carbapenemase gene, while one isolate of another clone (clone L) carried the
bla
OXA-72
carbapenemase gene. Only 1 isolate of clone Q carried the
bla
IMP-8
metallo-β-lactamase gene, located in a class 1 integron. Of 221 isolates, 77.8% carried
bla
PER-1
-like genes. Eleven different structures of class 1 integrons were detected, and most integrons carried genes mediating resistance to aminoglycosides, rifampin, and chloramphenicol. These findings indicated clonal spread of imipenem-resistant
Acinetobacter
spp. and wide dissemination of the OXA-23 carbapenemase in China.
Delineation of Species-Specific Binding Properties of the CspZ Protein (BBH06) of Lyme Disease Spirochetes: Evidence for New Contributions to the Pathogenesis of
Borrelia
spp
Authors: Rogers Elizabeth A. , Marconi Richard T. 
Published: September 2007

ABSTRACT

Borrelia burgdorferi
CspZ (TIGR open reading frame designation, BBH06) is part of a functionally related group of proteins that bind one or more members of the factor H (FH) protein family. In this report we assess the conservation, distribution, properties, and ligand binding abilities of CspZ from the three main
Borrelia
species associated with Lyme disease infections in humans. CspZ (also referred to as BbCRASP-2 in the literature) was found to be highly conserved at the intraspecies level but divergent at the interspecies level. All CspZ orthologs that originated from
B. burgdorferi
isolates bound FH from a diverse group of mammals. In contrast, CspZ derived from
B. garinii
and
B. afzelii
did not. Regardless of the
Borrelia
species of origin, all CspZ proteins tested bound to unknown ∼60-kDa serum proteins produced by different mammals. To further define the molecular basis for the differential binding of CspZ orthologs to host proteins, DNA sequence, truncation, and site-directed mutagenesis analyses were performed. DNA sequence analyses revealed that
B. garinii
and
B. afzelii
CspZ orthologs possess a 64-amino-acid N-terminal domain that is absent from
B. burgdorferi
CspZ. However, binding analyses of recombinant proteins revealed that this domain does not in and of itself influence ligand binding properties. Truncation and mutagenesis analyses further revealed that the key determinants required for ligand binding are discontinuous and that the presentation of the ligand binding pocket is dependent on alpha helices with high coiled-coil formation probability. The data presented here provide insight into the molecular basis of CspZ-ligand interactions and suggest that CspZ orthologs from diverse
Borrelia
species can contribute to the host-pathogen interaction through their interaction with serum proteins.
Effects of Aprotinin on Gene Expression and Protein Synthesis After Ischemia and Reperfusion in Rats
Authors: Buerke Michael , Pruefer Diethard , Sankat Dennis , Carter Justin M. , Buerke Ute , Russ Martin , Schlitt Axel , Friedrich Ivar , Börgermann Jochen , Vahl Christian F. , Werdan Karl 
Published: September 2007

Background—Reperfusion injury of ischemic myocardium has been attributed to neutrophil infiltration, inflammatory activation and cardiac necrosis/apoptosis. Serine protease inhibition with aprotinin is cardioprotective, but the mechanism is unknown.Methods and Results—We studied aprotinin in a rat model of myocardial ischemia for 20 minutes and reperfusion for 20 minutes, 8 hours or 24 hours. Aprotinin (20 000 IU/kg) given 5 minutes before reperfusion significantly reduced leukocyte accumulation (P<0.01), myocardial injury (determined by CK depletion,P<0.01) and myocyte apoptosis (P<0.05) compared with vehicle treated rats. Differential gene expression analysis showed myocardial ischemia plus reperfusion increased expression of proinflammatory genes like P-selectin, E-selectin, intercellular adhesion molecule, tumor necrosis factor-α, tumor necrosis factor-α receptor, interleukin-6, monocyte chemoattractant protein-1, p53, and Fas (CD59). Aprotinin before reperfusion suppressed expression of these inflammatory genes. Finally, differential protein expression analysis demonstrated increased intercellular adhesion molecule-1, tumor necrosis factor-α, and p53 after myocardial ischemia plus reperfusion, and this effect was diminished by aprotinin.Conclusions—We demonstrated myocardial ischemia plus reperfusion induced leukocyte accumulation, inflammation, gene expression, protein expression and finally tissue injury and showed aprotinin limiting reperfusion injury through each of these stages, even after 24 hours of reperfusion. This effect seems partly attributable to suppression of proinflammatory genes and leukocyte accumulation. This work casts further light on the complex signaling of ischemia and reperfusion.
International Social Work
Authors: Healy Lynne M. , Thomas Rebecca L. 
Published: September 2007

English This article analyzes the contributions of editorials and articles published in 50 years of International Social Work to knowledge about international social work and about the profession internationally. While sometimes too silent on major global social issues, the journal has enhanced understanding of the field and provides an important vehicle for international knowledge sharing. French Cet article analyse la contribution des éditoriaux et des articles parus à l'occasion du cinquantenaire de la revue International Social Work pour documenter le travail social international ainsi que le rayonnement de la profession à 'échelle internationale. Quoique parfois trop silencieuse sur d'importants enjeux mondiaux, la publication enrichit la compréhension du domaine et se révè le un véhicule incontournable pour le partage du savoir à l'échelle internationale. Spanish Este artículo analiza las contribuciones de editoriales y artículos publicados durante 50 añ os en International Social Work para conocer acerca del trabajo social internacional y acerca de la profesió n internacionalmente. Aunque algunas veces con demasiado silencio en los asuntos sociales globales, la revista ha ampliado la comprensió n del tema y proporciona una importante vía para compartir el conocimiento internacional.
Apraxia of speech: how reliable are speech and language therapists' diagnoses?
Authors: Mumby Katharyn , Bowen Audrey , Hesketh Anne 
Published: September 2007

Objective : To discover how reliably speech and language therapists could diagnose apraxia of speech using their clinical judgement, by measuring whether they were consistent (intra-rater reliability), and whether their diagnoses agreed (inter-rater reliability). Design : Video clips of people with communication difficulties following stroke were rated by four speech and language therapists who were given no definition of apraxia of speech, no training, and no opportunity for conferring. Settings : Videos were made of people following stroke in their homes. Ratings of the videos were carried out in the university lab under controlled conditions. Subjects : Forty-two people with communication difficulties such as aphasia, apraxia of speech and dysarthria took part, and four specialist speech and language therapists acted as raters. Main measure : Speech and language therapists' ratings of the presence and severity of apraxia of speech using videos. Results : Intra-rater reliability was high for diagnosing (1) the presence of apraxia of speech (Cohen's kappas ranging from 0.90 to 1.00; 0.93 overall), and (2) the severity of apraxia of speech (kappa 0.84 to 0.92; 0.90 overall). The inter-rater reliability was also high for both the presence of apraxia of speech (kappa 0.86) and severity of apraxia of speech (0.74). Conclusion : Despite controversy over its nature and existence, specialist speech and language therapists show high levels of agreement on the diagnosis of apraxia of speech using their clinical judgement.
Effects of acupuncture and sham acupuncture in addition to physiotherapy in patients undergoing bilateral total knee arthroplasty — a randomized controlled trial
Authors: Tsang Raymond Chi-Chung , Tsang Pui-Ling , Ko Chung-Yee , Kong Ben Chi-Hung , Lee Wing-Yee , Yip Ho-Ting 
Published: September 2007

Objective: To compare the acute effects of acupuncture with sham acupuncture on knee pain, range of motion and ambulation in patients with knee osteoarthritis undergoing bilateral total knee arthroplasty, when added to a standard postoperative physiotherapy programme. Design: Prospective patient- and assessor-blinded randomized controlled trial. Setting: Acute inpatient physiotherapy department. Patients: Thirty patients (24 women and 6 men) undergoing bilateral total knee arthroplasty were included for final analysis in the study. Interventions: Both groups received a standard postoperative physiotherapy programme. Each patient was also given either 10 sessions of acupuncture or sham acupuncture within two weeks. Main outcome measures: The primary outcome measures were the levels of pain at rest and at maximum after exercise measured by the numeric pain rating scale. Other outcome measures included active and passive ranges of knee motion measured by standard goniometer, and ambulation measured by the timed up-and-go test. Results: Thirty-six patients were recruited at the start of the study with 18 patients allocated to the acupuncture group and another 18 patients to the sham acupuncture group. On postoperative day 15, there were 30 patients with complete data; three patients in each group dropped out from the study. The mean differences (95% confidence interval (CI)) in overall averages of postoperative mean pain levels were 0.4 (—0.6 to 1.3) and —0.8 (—2.0 to 0.4) at rest and at maximum respectively. There were no significant differences in the active and passive ranges of knee motion and the time for the timed up-and-go test between the two groups. Conclusion: There is no difference between the acute effects of acupuncture and sham acupuncture in addition to standard postoperative physiotherapy programme in patients with knee osteoarthritis undergoing bilateral total knee arthroplasty.
Discounting the future, yet again
Authors: Brennan Geoffrey 
Published: September 2007

The question of `discounting the future' is one on which philosophers and economists have divergent professional views. There is a lot of talking at cross-purposes across the disciplinary divide here; but there is a fair bit of confusion (I think) within disciplines as well. My aim here is essentially clarificatory. I draw several distinctions that I see as significant: • between inter-temporal and intergenerational questions • between price (discount rate) and quantity (inter-temporal and intergenerational allocations) as the ethically relevant magnitude, and • between price change and preference change as the primary instrument of change. I show that discounting does not violate the principle of inter-temporal and intergenerational neutrality, but I also cast some doubt on whether making adequate allowance for future generations has really been the problem that economists and philosophers seem to have taken it to be.
An examination of the efficiency of the sequential parallel design in psychiatric clinical trials
Authors: Tamura Roy N , Huang Xiaohong 
Published: September 2007

Background Psychiatric clinical trials have a high failure rate, even among agents which are known to be effective. Because of this high failure rate, a novel clinical trial design has been proposed which incorporates a second phase in which non-responders to placebo are randomly reassigned to drug or placebo. Purpose The purpose of this research is to examine the efficiency of this new design compared to the conventional two arm clinical trial. We consider both binary and continuous endpoints. Methods The limiting distribution of a class of weighted average test statistics is obtained for the binary case which allows analytic calculation of the power for a given set of parameters. For the continuous case, we examine the efficiency of seemingly unrelated regression and a weighted average statistic via simulation. Results The novel design reduces the sample size 20—25% compared to the standard design under a wide range of parameters. Limitations There are no actual trials with the novel design therefore assumptions of the effect size across two periods for actual psychiatric agents is unknown. Conclusions The new design reduces sample size which in turn should reduce the cost of clinical trials. Further refinements of the design are possible including alternative test statistics and incorporation of additional data from placebo responders. Clinical Trials 2007; 4: 309—317. http://ctj.sagepub.com