bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral diadochokinetic rates for normal Thai children
Authors: Prathanee Benjamas , Thanaviratananich Sangaunsak , Pongjanyakul Amonrat 
Published: January 2004

AbstractBackground: The diadochokinetic (DDK) rate represents an index for assessing motor skills. It is commonly used in routine clinical evaluation of diseases of the central nervous system, disturbances of the peripheral sensory motor formations and immaturity of the speech mechanism. Oral DDK rates are a popular guideline for the assessment, diagnosis and treatment of patients with a neurological deficit of the speech mechanism. Baseline DDK rates have been published for English‐speaking children, but not for Thai‐speaking children. Thailand is situated in South East Asia, and the language belongs to the monosyllabic, tonal, Sino‐Tibetan group with extensive multisyllabic borrowings from the non‐tonal, Pali‐Sanskrit group.Aims: To assess the oral DDK rates for normal Thai children aged between 6 and 13 attending primary schools in order to establish a baseline for assessing, diagnosing and treating patients.Methods & Procedures: Subjects included 197 students who repeated, in rapid succession, specified sounds representing different levels of physiologic complexity, as indicated by differences in the developmental schedule, articulatory placement and syllabic content. Twenty syllable repetitions were required for monosyllabic utterances, 15 for bisyllablics and 10 for trisyllablics. Visi Pitch® Analysis was used to calculate the average time that subjects took to produce the sounds.Outcomes & Results: The time taken for the lip functions , /a:‐u:/, /u:‐i/ and /i:‐a:/ averaged 4.55, 6.67, 7.53 and 7.27 seconds, respectively. The tongue functions and click averaged 4.58, 4.82, 4.85 and 5.87 seconds, respectively. Tongue movement side‐to‐side between the corners of the mouth averaged 8.73 seconds, while the lip–tongue functions and were 6.97, 7.52 and 6.85 seconds, respectively. Sex and age influenced oral DDK time. The findings differ from those reported for English‐speaking children.Conclusions: A basis for assessment of children with neuromotor deficits or oral structure impairment is provided for both Thai and South East Asian children with similar physiological development and languages with similar sounds.
Prosody in autism spectrum disorders: a critical review
Authors: McCann Joanne , Peppé Sue 
Published: January 2004

AbstractBackground: Many individuals with autism spectrum disorders present with unusual or odd‐sounding prosody. Despite this widely noted observation, prosodic ability in autism spectrum disorders is often perceived as an under‐researched area.Aims: This review seeks to establish whether there is a prosodic disorder in autism, what generalizations can be made about its various manifestations and whether these manifestations vary according to the diagnosis. A literature review was carried out to establish what areas of prosody in autism spectrum disorders have been researched to date, what the findings have been and to determine what areas are yet to be researched.Main contribution: It is shown that prosody in autism spectrum disorders is an under‐researched area and that where research has been undertaken, findings often conflict. The findings of these conflicting studies are compared and recommendations are made for areas of future research.Conclusions: Research in this area has covered mostly prosodic expression, although some more recent studies cover comprehension, processing and the relationship of receptive prosodic ability to theory of mind. Findings conflict and methodology varies greatly.
Providing an equitable service to bilingual children in the UK: a review
Authors: Stow Carol , Dodd Barbara 
Published: January 2004

AbstractBackground: The UK is a multicultural, multilingual society and the majority of paediatric speech and language therapists in England have at least one bilingual child on their caseload. There are many imperatives driving the profession to provide an equitable service for bilingual children. Evidence is beginning to emerge, however, that bilingual children with specific language impairment are not being identified and are, therefore, not accessing services. The situation facing clinicians in the UK is not unique: it is mirrored around the world.Aims: This paper reviews the literature relating to speech and language services for bilingual children and begins by providing an overview of the forces driving the need to provide equity of service. All aspects of the therapeutic process are then examined, from referral to therapy, in order to identify features that are regarded as best practice. Whilst the focus is on delivery of services in the UK, research findings from around the world are considered.Main contribution: Certain themes emerged during the review and their implications are discussed. In particular, the need for assessment tools, training and research is highlighted.Conclusions: Features indicative of best practice are highlighted and tentative suggestions made that would enable services to address the challenges of serving bilingual paediatric caseloads.
Protection from harm: the experience of adults after therapy with prolonged‐speech
Authors: Cream Angela , Onslow Mark , Packman Ann , Llewellyn Gwynnyth 
Published: January 2004

AbstractBackground: It is well documented that adults can control stuttering if they use certain novel speech patterns referred to generically as prolonged‐speech (PS). These speech patterns were refined in the 1960s and developed into behavioural treatment programmes. The bulk of available PS treatment research has focused on speech parameters thought to reflect favourable treatment outcome. Considering this, and that post‐treatment relapse is known to be common, clinicians and researchers could be usefully informed by knowledge about the experiences of those who receive these treatments. Subsequently, they could use such information in attempts to control stuttering in their clients. Yet, at present, systematic research on this topic is scant.Aims: The continued development of PS treatments could be usefully informed by research into the experiences of those who use PS to control stuttering. Hence, that is the topic of the present report.Methods & Procedures: The method used was phenomenology. Participants were a purposive sample of 10 people who had received PS treatment. During a 2‐year period, a collaborative approach to the study of the topic was developed between the participants and interviewer. Interviews were from 1.5 to 2 hours, and a total of 34 interviews and discussions were undertaken with participants. Transcripts of these were used to generate text from which themes were identified using line‐by‐line, holistic and selective approaches.Outcomes & Results: The main findings were that even after therapy with PS there is a continued risk of stuttering occurring, and although adults have the novel experience of controlling stuttering, they also continue to experience feeling different from those who do not stutter, which may be exacerbated after therapy. Given the negative consequences associated with stuttering and feeling different, the essence of the experience after therapy with PS is that adults use their own resources to integrate behavioural skills with existing experiences in order to protect themselves from the harm of stuttering as best they can. PS changes speech, but not the dynamic and often unpredictable communication situations of everyday life. Hence, the maximum benefits of PS are attained when clients use a strategic approach to control stuttered speech and daily communication.Conclusions: These findings are consistent with the results of existing outcome research as well as with other current research from the present group. Their implications are discussed in relation to the structure of PS treatments as well as in relation to future PS outcome research. The clinical implications of these findings are discussed in terms of informing prospective clients of the experiential consequences of PS, selecting clients who might benefit from PS and in terms of assisting clients to achieve optimal benefits from PS.
Pharmacodynamics of S-3578, a Novel Cephem, in Murine Lung and Systemic Infection Models
Authors: Miyazaki Shuichi , Okazaki Kenichi , Tsuji Masakatsu , Yamaguchi Keizo 
Published: January 2004

ABSTRACT

S-3578 is a novel beta-lactam with enhanced activity against drug-resistant gram-positive cocci such as methicillin-resistant
Staphylococcus aureus
(MRSA). We used murine penicillin-resistant
Streptococcus pneumoniae
lung infection and neutropenic murine systemic MRSA infection models to determine the pharmacokinetic (PK)-pharmacodynamic (PD) parameter that best correlated with efficacy. Pharmacokinetic studies revealed that the maximum concentration in serum/dose values for S-3578 and cefepime in plasma in the lung infection model were 1.21 to 1.54 and 0.97 to 1.29, respectively; those for S-3578 in plasma in the systemic infection model were 0.78 to 1.02. The area under the concentration-time curve (AUC)/dose values for S-3578 and cefepime in plasma in the lung infection model were 0.98 to 1.13 and 0.77 to 1.04, respectively, and those for S-3578 in plasma in the systemic infection model were 1.03 to 1.11. The half-lives of S-3578 and cefepime in plasma in the lung infection model were 0.29 to 0.38 and 0.29 to 0.34, respectively, and those of S-3578 in plasma in the systemic infection model were 0.40 to 0.61. The time above the MIC was the PK-PD parameter that best correlated with efficacy in the murine lung infection model (

R
2

= 84 and 92% for S-3578 and cefepime in plasma, respectively). There was a twofold increase in the dose of S-3578 in the systemic infection model compared to that in the pneumonia model, yet the AUCs were the same. This may be due to the different MICs for the two pathogens.
PBP 2a Mutations Producing Very-High-Level Resistance to Beta-Lactams
Authors: Katayama Yuki , Zhang Hong-Zhong , Chambers Henry F. 
Published: January 2004

ABSTRACT

Resistance to the beta-lactam class of antibiotics in methicillin-resistant
Staphylococcus aureus
(MRSA) is mediated by PBP 2a, a synthetic bacterial cell wall penicillin-binding protein with a low affinity of binding to beta-lactams that is encoded by
mecA
. Beta-lactams that bind to PBP 2a with a high affinity and that are highly active against MRSA are under development. The potential for the emergence of resistance to such compounds was investigated by passage of homogeneous MRSA strain COL in L-695,256, an investigational carbapenem. A highly resistant mutant, COL52, expressed PBP 2a in which a two-amino-acid deletion mutation and three single-amino-acid substitution mutations were present. To examine the effects of these mutations on the resistance phenotype and PBP 2a production, plasmids carrying (i) PBP 2a with two or three of the four mutations, (ii) wild-type PBP 2a, or (iii) COL52 PBP 2a were introduced into methicillin-susceptible COL variants COLnex and COL52ex, from which the staphylococcus cassette chromosome
mec
(SCC
mec
) has been excised, as indicated by the “ex” suffix. Two amino acids substitutions, E→K
237
within the non-penicillin-binding domain and V→E
470
near the SDN
464
conserved penicillin-binding motif in the penicillin-binding domain in COL52, were important for high-level resistance. The highest level of resistance was observed when all four mutations were present. The emergence of PBP 2a-mediated resistance to beta-lactams that bind to PBP 2a with a high affinity is likely to require multiple mutations in
mecA
; chromosomal mutations appear to have a minor role.
Reemergence of Macrolide Resistance in Pharyngeal Isolates of Group A Streptococci in Southwestern Pennsylvania
Authors: Green Michael , Martin Judith M. , Barbadora Karen A. , Beall Bernard , Wald Ellen R. 
Published: January 2004

ABSTRACT

We previously reported on the emergence of macrolide-resistant pharyngeal isolates of group A streptococci (GAS) in our community. The purpose of the present study was to track longitudinal trends in macrolide resistance in these isolates in southwestern Pennsylvania. Testing for susceptibility to erythromycin and clindamycin was performed for all pharyngeal GAS isolates recovered at the Children's Hospital of Pittsburgh and a local pediatric practice between September 2001 and May 2002. Macrolide resistance phenotypes and genotypes were determined by double-disk diffusion and PCR, respectively. Strain relatedness was determined by field inversion gel electrophoresis and
emm
gene sequence typing. A total of 708 isolates of GAS were recovered during the study period; 68 (9.6%) were macrolide resistant, while all isolates were sensitive to clindamycin. The monthly prevalence of macrolide resistance ranged from 0 to 41%. Only 21 of 573 (3.7%) strains recovered from September 2001 through March 2002 were macrolide resistant. A sudden increase in the rate of macrolide resistance (47 of 135 isolates [35%]) was seen in April and May 2002. Sixty-two isolates demonstrated the M phenotype (resistance to macrolide antibiotics), and six isolates demonstrated the MLS
B
phenotype (resistance to most macrolide, lincosamide, and streptogramin B antibiotics); these isolates were confirmed to be
mef
(A) and
erm
(A), respectively. Three unique
mef
(A) clones and four unique
erm
(A) clones were identified among the resistant isolates. The MIC at which 50% of isolates are inhibited (MIC
50
) for the
mef
(A) strains was 16 μg/ml, while the MIC
50
for
erm
(A) strains was 8 μg/ml. The finding of high levels of macrolide resistance among pharyngeal isolates of GAS for a second successive year in our community raises the concern that this problem may be more common in the United States than was previously appreciated. Longitudinal surveillance of isolates from multiple centers is needed to define the prevalence of antimicrobial agent-resistant GAS in the United States.
Mechanism of Action of NB2001 and NB2030, Novel Antibacterial Agents Activated by β-Lactamases
Authors: Stone Geoffrey W. , Zhang Qin , Castillo Rosario , Doppalapudi V. Ramana , Bueno Analia R. , Lee Jean Y. , Li Qing , Sergeeva Maria , Khambatta Gody , Georgopapadakou Nafsika H. 
Published: January 2004

ABSTRACT

Two potent antibacterial agents designed to undergo enzyme-catalyzed therapeutic activation were evaluated for their mechanisms of action. The compounds, NB2001 and NB2030, contain a cephalosporin with a thienyl (NB2001) or a tetrazole (NB2030) ring at the C-7 position and are linked to the antibacterial triclosan at the C-3 position. The compounds exploit β-lactamases to release triclosan through hydrolysis of the β-lactam ring. Like cephalothin, NB2001 and NB2030 were hydrolyzed by class A β-lactamases (
Escherichia coli
TEM-1 and, to a lesser degree,
Staphylococcus aureus
PC1) and class C β-lactamases (
Enterobacter cloacae
P99 and
E. coli
AmpC) with comparable catalytic efficiencies (
k
cat
/

K
m

). They also bound to the penicillin-binding proteins of
S. aureus
and
E. coli
, but with reduced affinities relative to that of cephalothin. Accordingly, they produced a cell morphology in
E. coli
consistent with the toxophore rather than the β-lactam being responsible for antibacterial activity. In biochemical assays, they inhibited the triclosan target enoyl reductase (FabI), with 50% inhibitory concentrations being markedly reduced relative to that of free triclosan. The transport of NB2001, NB2030, and triclosan was rapid, with significant accumulation of triclosan in both
S. aureus
and
E. coli
. Taken together, the results suggest that NB2001 and NB2030 act primarily as triclosan prodrugs in
S. aureus
and
E. coli
.
Enhanced Saquinavir Exposure in Human Immunodeficiency Virus Type 1-Infected Patients with Diarrhea and/or Wasting Syndrome
Authors: Trout Hervé , Mentré France , Panhard Xavière , Kodjo Alissi , Escaut Lélia , Pernet Pascal , Gobert Jean-Gérard , Vittecoq Daniel , Knellwolf Anne-Laure , Caulin Charles , Bergmann Jean-François 
Published: January 2004

ABSTRACT

The protease inhibitor saquinavir was administered to 100 human immunodeficiency virus type 1 (HIV-1)-infected patients as a single 600-mg oral dose (hard gelatin capsules) with a standard breakfast, including 200 ml of grapefruit juice, during an open-label trial to assess whether diarrhea and/or wasting syndrome has consequences on its pharmacokinetics. Three groups of patients were enrolled: group 1, asymptomatic patients (
n
= 30); group 2, AIDS symptomatic patients without body weight loss or diarrhea (
n
= 37); and group 3, AIDS symptomatic patients with severe body weight loss and/or diarrhea (
n
= 33). Clinical and biological data (covariates) were collected. A population approach was performed with three blood samples per patient to estimate the mean population pharmacokinetic parameters (clearance [CL]/oral bioavailability [F],
V
/F,
k
a
, and lag time) and the derived ones (
k
el
,
C
max
,
T
max
, and area under the curve [AUC]). The relationships between groups, exposure (i.e., estimated individual post hoc AUCs), and covariates were explored by using multiple linear regressions. A significant increase in median AUCs (165, 349, and 705 ng · h · ml
−1
for groups 1, 2, and 3, respectively [
P
< 0.0001]) was observed. The enhancement in saquinavir exposure could be due to the destruction of the transporters in enterocytes and/or to the enlargement of their tight junctions, allowing a paracellular crossing of saquinavir as the illness spreads. Because of grapefruit juice intake by every patient, no implication of CYP3A4 could be assessed. These results strongly suggest that, despite its low intrinsic oral bioavailability, saquinavir can be considered as a relevant treatment for HIV-1-infected patients with diarrhea and/or wasting syndrome. This must be evaluated in a long-term period.
Subinhibitory Concentrations of Linezolid Reduce
Staphylococcus aureus
Virulence Factor Expression
Authors: Bernardo Katussevani , Pakulat Norbert , Fleer Silke , Schnaith Annabelle , Utermöhlen Olaf , Krut Oleg , Müller Stefan , Krönke Martin 
Published: January 2004

ABSTRACT

The influence of the antibiotic linezolid on the secretion of exotoxins by
Staphylococcus aureus
was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis combined with matrix-assisted laser desorption ionization-time of flight mass spectrometry and Western blot analysis.
S. aureus
suspensions were treated with grading subinhibitory concentrations of linezolid (12.5, 25, 50, and 90% of MIC) at different stages of bacterial growth (i.e., an optical density at 540 nm [OD
540
] of 0.05 or 0.8). When added to
S. aureus
cultures at an OD
540
of 0.05, linezolid reduced in a dose-dependent manner the secretion of specific virulence factors, including staphylococcal enterotoxin A (SEA) and SEB, bifunctional autolysin, autolysin, protein A, and alpha- and beta-hemolysins. In contrast, other presumably nontoxic exoproteins remained unchanged or even accumulated in supernatants in the presence of linezolid at a 90% MIC. Similarily, when added at OD
540
of 0.8, that is, after quorum sensing, linezolid reduced the release of virulence factors, whereas the relative abundance of nontoxic exoproteins such as triacylglycerol lipase, glycerol ester hydrolase, DnaK, or translation elongation factor EF-Tu was found to be increased. Consistently, linezolid reduced in a dose-dependent manner the tumor necrosis factor-inducing activity secreted by
S. aureus
into the culture supernatants. The results of our study suggest that the expression of virulence factors in
S. aureus
is especially sensitive to the inhibition of protein synthesis by linezolid, which should be an advantage in the treatment of infections with toxin-producing
S. aureus
.
Functional Angucycline-Like Antibiotic Gene Cluster in the Terminal Inverted Repeats of the
Streptomyces ambofaciens
Linear Chromosome
Authors: Pang Xiuhua , Aigle Bertrand , Girardet Jean-Michel , Mangenot Sophie , Pernodet Jean-Luc , Decaris Bernard , Leblond Pierre 
Published: January 2004

ABSTRACT

Streptomyces ambofaciens
has an 8-Mb linear chromosome ending in 200-kb terminal inverted repeats. Analysis of the F6 cosmid overlapping the terminal inverted repeats revealed a locus similar to type II polyketide synthase (PKS) gene clusters. Sequence analysis identified 26 open reading frames, including genes encoding the β-ketoacyl synthase (KS), chain length factor (CLF), and acyl carrier protein (ACP) that make up the minimal PKS. These KS, CLF, and ACP subunits are highly homologous to minimal PKS subunits involved in the biosynthesis of angucycline antibiotics. The genes encoding the KS and ACP subunits are transcribed constitutively but show a remarkable increase in expression after entering transition phase. Five genes, including those encoding the minimal PKS, were replaced by resistance markers to generate single and double mutants (replacement in one and both terminal inverted repeats). Double mutants were unable to produce either diffusible orange pigment or antibacterial activity against
Bacillus subtilis
. Single mutants showed an intermediate phenotype, suggesting that each copy of the cluster was functional. Transformation of double mutants with a conjugative and integrative form of F6 partially restored both phenotypes. The pigmented and antibacterial compounds were shown to be two distinct molecules produced from the same biosynthetic pathway. High-pressure liquid chromatography analysis of culture extracts from wild-type and double mutants revealed a peak with an associated bioactivity that was absent from the mutants. Two additional genes encoding KS and CLF were present in the cluster. However, disruption of the second KS gene had no effect on either pigment or antibiotic production.
Genetic Environment and Transcription of
ampC
in an
Acinetobacter baumannii
Clinical Isolate
Authors: Segal Heidi , Nelson E. C. , Elisha B. Gay 
Published: January 2004

ABSTRACT

An
ampC
gene was cloned from a clinical isolate of
Acinetobacter baumannii
(strain RAN). DNA sequencing and primer extension studies showed that
ampC
is transcribed from a promoter contained within a putative insertion sequence element which has been found to abut several different genes in
Acinetobacter
spp.
Penetration of Linezolid into the Anterior Chamber (Aqueous Humor) of the Human Eye after Intravenous Administration
Authors: Vázquez E. García , Mensa J. , López Y. , Couchard P. Díaz , Soy D. , Fontenla J. R. , Sarasa M. , Carné X. , Montull E. 
Published: January 2004

ABSTRACTWe determined the linezolid concentrations in serum samples and aqueous humors (AHs) from 21 patients undergoing cataract extraction. Cataract removal was performed at various times (from 60 to 270 min) after the end of a 30-min infusion of 600 mg of linezolid. Serum samples were obtained 1 h after the end of linezolid administration to determine the maximum concentration of linezolid (Cmax); AHs and a second serum sample were taken simultaneously during the operation, and the concentrations of linezolid in AH (CAH) and serum (CS) were determined. The mean CAH1 h after linezolid administration was 4.94 μg/ml, and the mean ratio of CAHto CS(R= CAH/CS) was 0.43. All patients had a CAHof >2 μg/ml, which was higher than the MIC at which 90% ofStaphylococcus epidermidisstrains are inhibited.
Antimicrobial Activity and Bacterial-Membrane Interaction of Ovine-Derived Cathelicidins
Authors: Anderson Rachel C. , Hancock Robert E. W. , Yu Pak-Lam 
Published: January 2004

ABSTRACT
Three ovine-derived cathelicidins, SMAP29, OaBac5mini, and OaBac7.5mini, were compared with respect to their antibacterial activities and interactions with membranes. SMAP29 was confirmed to be α-helical, broad spectrum, and able to disrupt both the outer and the cytoplasmic membranes at relatively low concentrations. In contrast, the two proline- and arginine-rich OaBac peptides had more-modest antibacterial activities, reduced levels of lipopolysaccharide binding, and a lesser ability to depolarize the cytoplasmic membrane, consistent with a cytoplasmic target.