bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental factors influencing skeletal grain sediment associations: a critical review of Miocene examples from the western Mediterranean
Authors: Pomar Luis , Brandano Marco , Westphal Hildegard
Published: May 2004

The presence of foramol, rhodalgal and bryomol skeletal grain associations in ancient shallow‐marine limestones is commonly interpreted as evidence for non‐tropical palaeoclimate, despite temperature being only one of several factors influencing skeletal grain associations. Such interpretations neglect the multitude of factors other than temperature that influence carbonate‐producing biota. These include nutrients, water energy, water transparency, depth of the sea floor, salinity, oxygen, Ca2+ and CO2 concentrations, Mg/Ca ratio, alkalinity, substrate requirements, competitive displacement as well as biological and evolutionary trends. This uniformitarian approach also disregards the probability that conditions of present‐day biological systems may not be representative of past conditions of analogous systems. Here, the importance of considering these other factors is illustrated through two examples of carbonate platforms in the western Mediterranean. These platforms are dominated by foramol, rhodalgal and bryomol associations of Miocene age in spite of having formed in tropical conditions. The platforms discussed are: (1) the Lower Tortonian ramp on Menorca, Balearic Islands; and (2) the Lower–Middle Miocene ramps of the central Apennines, Italy. Evidence for tropical conditions in the Mediterranean during the period of growth of these platforms is provided by species of red algae and larger foraminifera, by data from coeval continental basins and by global oxygen isotope data.
Viscoelastic behaviour and temporal fractal properties of lherzolite and marble: possible extrapolation from experimental results to the geological time‐scale
Authors: Kawada Yusuke , Nagahama Hiroyuki
Published: May 2004

The viscoelastic relaxation behaviour of lherzolite and marble and their temporal fractal properties are studied. Based on the high‐temperature viscoelastic behaviour for these rock types derived from the time–temperature superposition principle, the relaxation function for the viscoelastic behaviour of lherzolite and marble can be expressed as a flow law from a power‐law function of temperature‐reduced time given by normalizing the various temperature behaviours, with a non‐integer exponent. The relaxation function is thus time‐scale invariant, i.e. there is a temporal fractal property to the temperature‐reduced time. Their rheological behaviour over geological time‐scales at low temperature can be extrapolated from the experimental high‐temperature behaviour based on the temporal fractal property. Our derived flow law satisfies not only transient behaviour but also steady‐state behaviour.
The Permian–Triassic boundary in the Central European Basin: magnetostratigraphic constraints
Authors: Nawrocki Jerzy
Published: May 2004

Some stratigraphic interpretations concerning correlation of the Permian–Triasssic transition beds from the Central European, Boreal and Tethyan Basins are inconsistent with the existing magnetostratigraphic data. In addition, the suggestion that the Permian–Triassic boundary is located in the lower part of the Calvörde Formation of the Central European Basin cannot be supported by magnetostratigraphic data. Results of magnetostratigraphic correlation show that in the Polish part of the Central European Basin the Permian–Triassic boundary is close to the boundary between the uppermost Zechstein and the Lower Buntsandstein. It is located within the reversed magnetozone ‘PZr1’ identified in the upper part of the Rewal Formation. In the German part of the Central European Basin the Permian–Triassic boundary can be located within the reversed magnetozone ‘zrz’ that covers most of the Bröckelschiefer. A higher stratigraphic location of this boundatry, i.e. inside the lowermost Buntsandstein, requires a reversed polarity record to be found within the basal Triassic normal polarity zone.
Identification of the Armillaria root rot pathogen in Ethiopian plantations
Authors: Gezahgne A. , Coetzee M. P. A. , Wingfield B. D. , Wingfield M. J. , Roux J.
Published: May 2004

Armillaria root rot is a well‐known disease on a wide range of plants, world‐wide. In Ethiopia, the disease has previously been reported on Pinus spp., Coffea arabica and on various native hardwoods. The causal agent of the disease has been attributed to Armillaria mellea, a species now known to represent a complex of many different taxa. The aim of this study was to determine the extent of Armillaria root rot and the identity of the Armillaria sp. in Ethiopian plantations. As part of a plantation disease survey in 2000 and 2001, samples were collected in plantations at and around Munessa Shashemene, Wondo Genet, Jima, Mizan and Bedele, in south and south‐western Ethiopia. Basidiocarps were collected and their morphology studied. Morphological identification was confirmed by sequencing the intergenic spacer (IGS‐1) region of the ribosomal rRNA operon and comparing data with published sequences of Armillaria spp. Armillaria isolates were collected from Acacia abyssinica, Pinus patula, Cedrela odorata and Cordia alliodora trees. Sporocarps were found on stumps of native Juniperus excelsa. Basidiocarp morphology and sequence data suggested that the fungus in Ethiopia is similar to that causing disease of Pinus spp. in South Africa and previously identified as A. fuscipes. This identification was confirmed for all isolates, based on sequence data. Armillaria fuscipes is known to be common in southern Africa. Its widespread occurrence in Ethiopia suggests that it is also the major cause of Armillaria root rot in that country.
Reaction of Armillaria ostoyae to forest soil microfungi
Authors: Kwaśna H. , Łakomy P. , Mallett K.
Published: May 2004

Fungi isolated from the oak (Quercus robur) rhizosphere were tested for their effects on rhizomorph formation and growth of 16 isolates of Armillaria ostoyae sampled in three localities in western Poland. The number of rhizomorphs, number of rhizomorph apices, and rhizomorph length and weight increased most in the presence of Penicillium lanosum, Penicillium notatum, Cylindrocarpon destructans, Penicillium spinulosum and Mycelium radicis atrovirens α and, to a lesser extent, in the presence of Nectria grammicospora. Inhibition of rhizomorph formation was caused by Trichoderma hamatum and Trichoderma viride in two A. ostoyae isolates and by M. radicis atrovirens α and P. spinulosum in one A. ostoyae isolate. It is suggested that variation in sensitivity to microbial stimulation within A. ostoyae is associated with the environmental and nutritional conditions of its original habitat. Isolates from nutrition‐rich localities, with 20% of the land area covered by deciduous trees, were particularly susceptible to stimulation by rhizosphere fungi.
Dothistroma (red‐band) needle blight of pines and the dothistromin toxin: a review
Authors: Bradshaw R. E.
Published: May 2004

Dothistroma (red‐band) needle blight has been a problem in plantations of exotic pines in the southern hemisphere for many decades. The prevalence of this disease is currently increasing in the northern hemisphere and is now affecting trees in their native ranges. The fungal pathogen Mycosphaerella pini with its anamorph Dothistroma pini, which is responsible for the disease, produces a toxin, dothistromin, that is closely related to the potent carcinogen, aflatoxin. Understandably this has provoked concern about possible effects on the health of forestry workers. This review gives a broad coverage of literature on both disease and toxin. The fungus has a complicated taxonomy with many synonyms and in most countries only the anamorph is found. It is a necrotrophic pathogen that kills needle tissue and completes its life cycle in the lesion thus formed. Dispersal of the disease is normally by rain splash of conidiospores but there is evidence that long range dispersal has occurred by transport of contaminated plant tissue and by wind/cloud dispersal of spores in air currents. The severity of disease is affected by humidity, temperature and light. There is variation in susceptibility of different Pinus species and some achieve increased resistance with age. The current method of control in southern hemisphere plantation forests is through spraying with copper fungicides and, with P. radiata, increased disease resistance has been achieved through a breeding programme. The dothistromin toxin is a difuroanthraquinone and is similar in structure to the aflatoxin precursor versicolorin B. Part of a gene cluster encoding dothistromin biosynthetic genes has been cloned and this has confirmed parallels between the dothistromin and aflatoxin biosynthetic pathways. Dothistromin produces damaging oxygen radicals by reductive oxygen activation rather than by photosensitization, but is also thought to exert its toxic effects on specific cellular targets. Studies have shown that dothistromin is a weak mutagen and clastogen and is therefore a potential carcinogen. Although the risks to forest workers are considered very low it is prudent to avoid unnecessary exposure during periods when dothistromin levels are likely to be at their peak.
Interdisciplinarity and the Discipline of Law
Authors: Vick Douglas W.
Published: May 2004

This article concerns the effects of interdisciplinary research conducted by academic lawyers on the legal discipline itself. It discusses the intellectual tension between the modes of legal analysis traditionally used by academic lawyers and the approach taken by interdisciplinary scholars, and how this tension is rooted in the challenges interdisciplinarity poses to widely‐accepted notions about the purposes of legal scholarship and the relationship between academic lawyers and the legal profession. The article considers the implications of legal interdisciplinarity in light of the cultural context from which legal interdisciplinarians emerge and how the relationship between legal scholarship and legal practice ultimately guarantees the continued existence of a distinct and coherent disciplinary identity for law.
Technologies, Security, and Privacy in the Post‐9/11 European Information Society
Authors: Levi Michael , Wall David S.
Published: May 2004

Since 11 September 2001, many ‘hard’ and ‘soft’ security strategies have been introduced to enable more intensive surveillance and control of the movement of `suspect populations'. Suicide bombings have since generated a step‐change in asymmetric threat analysis and public perceptions of risk. This article reviews how post‐9/11 ‘security’ issues intersect with existing and emerging technologies, particularly those relating to identity, location, home, and work that will form the backbone of the European Information Society. The article explores the complexities generated by the way that these technologies work, sites of nationalist resistance, and formal bureaucratic roles. Many of the planned surveillance methods and technologies are convergence technologies aiming to bring together new and existing data sources, but are unable to do so because of poor data quality and the difficulty of using the integrated data to reduce serious crime risks. The delay may enable legal compliance models to be developed in order to protect the principles of privacy that are set out in the ECHR and the EC Data Protection Directive. Though (moral) panics produce changes in law, the article emphasizes the constraining effects of law.
A Story of Miscarriage: Law in the Media
Authors: Nobles Richard , Schiff David
Published: May 2004

This article utilizes the work of the sociologist Niklas Luhmann in order to examine the relationship between law and the media. Luhmann views both law and the media as closed systems of communication, systems which cannot duplicate the meaning of each other's communications. After introducing Luhmann's approach to media reporting, and applying this to the relationship between law and media reporting on law, the article analyses a recent miscarriage of justice case. The case is that of the solicitor Sally Clark who was convicted of a double child killing. Although her first appeal was rejected she succeeded in a second appeal. Media reporting of Sally Clark's case is contrasted with the trial and Court of Appeal judgments to demonstrate the different basis upon which law and the media each construct communications about the same events
A Knowledge Transfer Strategy for Public Health Decision Makers
Authors: Dobbins M. , DeCorby K. , Twiddy T.
Published: May 2004

Purpose: The purpose of this study was to discover public health decision makers' preferences for content, format, and channels for receiving research knowledge, so as to begin development of a comprehensive national public health knowledge transfer strategy. A preliminary knowledge transfer strategy developed in part from the views expressed by public health decision makers in an earlier study (Dobbins et al. 2002b) was used as a foundation on which to base discussions. The research team believes strongly that consultation with potential users is crucial to ensure the conduct of relevant and timely research as well as the development of an effective knowledge transfer strategy.

Methods: Nine focus groups of five to seven participants were held in seven Canadian cities. Participants included medical officers of health, public health managers and directors, health promotion mangers, and health policymakers at provincial and federal levels. A semi‐structured, open‐ended interview guide was used to facilitate the discussion. The focus groups were audiotaped, and results were analyzed independently by two members of the research team who then developed key themes through a consensus process.

Results: Generally, participants spoke positively about the knowledge transfer strategy to which they were exposed. In addition, they supported the development of a registry of reviews evaluating the effectiveness of public health interventions rated by methodological quality of the evidence, with a summary statement of the reviews highlighting the results along with specific implications for practice. Participants also indicated they wanted to receive personalized updates of new reviews in their area of interest. Finally, the results highlighted a significant challenge related to knowledge management indicating opportunities for ongoing professional development and training.

Conclusions: These findings were used to create an online registry of reviews evaluating the effectiveness of public health and health promotion interventions. The registry is one component of a comprehensive national public health knowledge transfer strategy.
Determination of the In Vivo Pharmacodynamic Profile of Cefepime against Extended-Spectrum-Beta-Lactamase-Producing
Escherichia coli
at Various Inocula
Authors: Maglio Dana , Ong Christine , Banevicius Mary Anne , Geng Qiuming , Nightingale Charles H. , Nicolau David P.
Published: May 2004

Cefepime was evaluated in vivo against two inoculum sizes of four strains of
Escherichia coli
that produced extended-spectrum beta-lactamases (ESBLs) in a murine neutropenic thigh infection model to characterize the pharmacodynamic activity of cefepime in the presence of ESBL-producing bacteria and to evaluate if differences in lengths of cefepime exposure are required with various inocula. Three strains possessed a single enzyme each: TEM-10, TEM-12, and TEM-26. The fourth strain possessed two TEM-derived ESBLs and a third uncharacterized enzyme. Two non-ESBL-producing
E. coli
strains were included for comparison. Mice received various doses of cefepime to achieve a spectrum of percentages of time the drug was above the MIC (%
T
>MICs) for each isolate at both inocula. No significant difference in cefepime exposure was required to achieve similar bactericidal effects for ESBL- and non-ESBL-producing isolates when the starting inoculum was 10
5
CFU of
E. coli
per thigh. The increased MICs observed in vitro for the ESBL-producing strains at 10
7
CFU/ml did not predict the amount of exposure required to achieve a comparable level of bactericidal activity in vivo at the corresponding starting inoculum of 10
7
CFU/thigh. Compared to the cefepime exposure in tests with the lower inoculum (10
5
CFU/thigh), less exposure was required when the starting inoculum was 10
7
CFU/thigh (%
T
>MIC, 6% versus 26%), such that similar doses (in milligrams per kilogram of body weight) produced similar bactericidal effects with both inocula of ESBL-producing isolates. Equivalent exposures of cefepime produced similar effects against the microorganisms regardless of the presence of ESBL production. Pharmacodynamic profiling undertaken with conventional cefepime MIC determinations predicted in vivo microbial outcomes at both inoculum sizes for the ESBL-producing isolates evaluated in this study. These data support the use of conventional MIC determinations in the pharmacodynamic assessment of cefepime.
Anti-Inflammatory Effects of Moxifloxacin on Activated Human Monocytic Cells: Inhibition of NF-κB and Mitogen-Activated Protein Kinase Activation and of Synthesis of Proinflammatory Cytokines
Authors: Weiss Taly , Shalit Itamar , Blau Hannah , Werber Sara , Halperin Drora , Levitov Avital , Fabian Ina
Published: May 2004

We previously showed that moxifloxacin (MXF) exerts protective anti-inflammatory effects in immunosuppressed mice infected withCandida albicansby inhibiting interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-α) production in the lung. Immunohistochemistry demonstrated inhibition of nuclear factor (NF)-κB translocation in lung epithelium and macrophages in MXF-treated mice. In the present study we investigated the effects of MXF on the production of proinflammatory cytokines (i.e., IL-8, TNF-α, and IL-1β) by activated human peripheral blood monocytes and THP-1 cells and analyzed the effects of the drug on the major signal transduction pathways associated with inflammation: NF-κB and the mitogen-activated protein kinases ERK and c-Jun N-terminal kinase (JNK). The levels of IL-8, TNF-α, and IL-1β secretion rose 20- and 6.7-fold in lipopolysaccharide (LPS)-activated monocytes and THP-1 cells, respectively. MXF (5 to 20 μg/ml) significantly inhibited cytokine production by 14 to 80% and 15 to 73% in monocytes and THP-1 cells, respectively. In THP-1 cells, the level of NF-κB nuclear translocation increased fourfold following stimulation with LPS-phorbol myristate acetate (PMA), and this was inhibited (38%) by 10 μg of MXF per ml. We then assayed the degradation of inhibitor (I)-κB by Western blotting. LPS-PMA induced degradation of I-κB by 73%, while addition of MXF (5 μg/ml) inhibited I-κB degradation by 49%. Activation of ERK1/2 and the 46-kDa p-JNK protein was enhanced by LPS and LPS-PMA and was significantly inhibited by MXF (54 and 42%, respectively, with MXF at 10 μg/ml). We conclude that MXF suppresses the secretion of proinflammatory cytokines in human monocytes and THP-1 cells and that it exerts its anti-inflammatory effects in THP-1 cells by inhibiting NF-κB, ERK, and JNK activation. Its anti-inflammatory properties should be further assessed in clinical settings.
Reactivity of Platelia
Aspergillus
Galactomannan Antigen with Piperacillin-Tazobactam: Clinical Implications Based on Achievable Concentrations in Serum
Authors: Singh Nina , Obman Asia , Husain Shahid , Aspinall Sherrie , Mietzner Sue , Stout Janet E.
Published: May 2004

The possible reactivities of commonly used antibiotics of fungal, nonfungal, and nonmicrobial or synthetic sources with the Platelia
Aspergillus
galactomannan assay were assessed. For drugs that tested positive, the minimal concentration of the antibiotic in serum that yielded a positive test (index, >0.5) was determined. At undiluted concentrations, piperacillin and multiple lots of piperacillin-tazobactam tested positive, whereas amoxicillin, ampicillin-sulbactam, nafcillin, cefazolin, ceftazidime, erythromycin, gentamicin, and levofloxacin tested negative. All three lots of piperacillin-tazobactam and all bags within each lot tested positive, with a mean index value of 5.168. At achievable concentrations in serum, however, only one of three lots of piperacillin-tazobactam yielded a positive test. Concentrations of 75, 150, and 300 μg/ml of serum tested positive with the Platelia
Aspergillus
enzyme immunoassay, whereas lower concentrations, mimicking the trough levels, tested negative. Thus, while achievable serum piperacillin-tazobactam concentrations may potentially result in a positive test for galactomannan, the timing of the collection of serum samples from patients may influence the test results, with reactivity being less likely in samples collected at trough levels or prior to the administration of a dose of the antibiotic.
Susceptibility of
Candida
Species to Photodynamic Effects of Photofrin
Authors: Bliss Joseph M. , Bigelow Chad E. , Foster Thomas H. , Haidaris Constantine G.
Published: May 2004

The in vitro susceptibility of pathogenic
Candida
species to the photodynamic effects of the clinically approved photosensitizing agent Photofrin was examined. Internalization of Photofrin by
Candida
was confirmed by confocal fluorescence microscopy, and the degree of uptake was dependent on incubation concentration. Uptake of Photofrin by
Candida
and subsequent sensitivity to irradiation was influenced by culture conditions. Photofrin uptake was poor in
C. albicans
blastoconidia grown in nutrient broth. However, conversion of blastoconidia to filamentous forms by incubation in defined tissue culture medium resulted in substantial Photofrin uptake. Under conditions where Photofrin was effectively taken up by
Candida
, irradiated organisms were damaged in a drug dose- and light-dependent manner. Uptake of Photofrin was not inhibited by azide, indicating that the mechanism of uptake was not dependent on energy provided via electron transport. Fungal damage induced by Photofrin-mediated photodynamic therapy (PDT) was determined by evaluation of metabolic activity after irradiation. A strain of
C. glabrata
took up Photofrin poorly and was resistant to killing after irradiation. In contrast, two different strains of
C. albicans
displayed comparable levels of sensitivity to PDT. Furthermore, a reference strain of
C. krusei
that is relatively resistant to fluconazole compared to
C. albicans
was equally sensitive to
C. albicans
at Photofrin concentrations of ≥3 μg/ml. The results indicate that photodynamic therapy may be a useful adjunct or alternative to current anti-
Candida
therapeutic modalities, particularly for superficial infections on surfaces amenable to illumination.
Biochemical Characterization of the Naturally Occurring Oxacillinase OXA-50 ofPseudomonas aeruginosa
Authors: Girlich Delphine , Naas Thierry , Nordmann Patrice
Published: May 2004

TheblaOXA-50gene (formerly known as the PA5514 gene) is an oxacillinase gene identified in silico in the genome ofPseudomonas aeruginosaPAO1. By using a mutant strain ofP. aeruginosaPAO1 that had an inactivatedblaAmpCcephalosporinase gene, theblaOXA-50gene was shown to be expressed constitutively inP. aeruginosa. This β-lactamase gene was cloned onto a multicopy plasmid and expressed inP. aeruginosaandEscherichia coli. It conferred decreased susceptibility to ampicillin and ticarcillin and, interestingly, to moxalactam and meropenem inP. aeruginosabut not inE. coli. Overexpression and purification enabled us to determine the molecular mass (25 kDa), the pI value (8.6), and the hydrolysis spectrum of the OXA-50 β-lactamase. It is a narrow-spectrum oxacillinase that uncommonly hydrolyzes imipenem, although at a low level. Very similar oxacillinase genes were identified in allP. aeruginosaisolates from various geographical origins tested. The weak variability of the nucleotide sequence of this gene (0 to 2%) corresponded to that found for the naturally occurringblaAmpCcephalosporinase gene ofP. aeruginosa. The study indicated thatP. aeruginosaharbors two naturally encoded β-lactamase genes, one of which encodes an inducible cephalosporinase and the other of which encodes a constitutively expressed oxacillinase.
Novel Pharmacokinetic-Pharmacodynamic Model forPrediction of Outcomes with an Extended-Release FormulationofCiprofloxacin
Authors: Meagher Alison K. , Forrest Alan , Dalhoff Axel , Stass Heino , Schentag Jerome J.
Published: May 2004

The
pharmacokinetics of an extended-release (XR) formulation of
ciprofloxacin has been compared to that of the immediate-release (IR)
product in healthy volunteers. The only significant difference in
pharmacokinetic parameters between the two formulations was seen in the
rate constant of absorption, which was approximately 50% greater
with the IR formulation. The geometric mean plasma ciprofloxacin
concentrations were applied to an in vitro
pharmacokinetic-pharmacodynamic model exposing three different clinical
strains of
Escherichia coli
(MICs, 0.03, 0.5, and 2.0
mg/liter) to 24 h of simulated concentrations in plasma. A
novel mathematical model was derived to describe the time course of
bacterial CFU, including capacity-limited replication and first-order
rate of bacterial clearance, and to model the effects of ciprofloxacin
concentrations on these processes. A “mixture model”
was employed which allowed as many as three bacterial subpopulations to
describe the total bacterial load at any moment. Comparing the two
formulations at equivalent daily doses, the rates and extents of
bacterial killing were similar with the IR and XR formulations at MICs
of 0.03 and 2.0 mg/liter. At an MIC of 0.5 mg/liter, however, the
1,000-mg/day XR formulation showed a moderate advantage in
antibacterial effect: the area under the CFU-time curve was 45%
higher for the IR regimen; the nadir log CFU and 24-h log CFU values
for the IR regimen were 3.75 and 2.49, respectively; and those for XR
were 4.54 and 3.13, respectively. The mathematical model explained the
differences in bacterial killing rate for two regimens with identical
AUC/MIC
ratios.
High Prevalence of Antimicrobial Resistance among Clinical
Streptococcus pneumoniae
Isolates in Asia (an ANSORP Study)
Authors: Song Jae-Hoon , Jung Sook-In , Ko Kwan Soo , Kim Na Young , Son Jun Seong , Chang Hyun-Ha , Ki Hyun Kyun , Oh Won Sup , Suh Ji Yoeun , Peck Kyong Ran , Lee Nam Yong , Yang Yonghong , Lu Quan , Chongthaleong Anan , Chiu Cheng-Hsun , Lalitha M. K. , Perera Jennifer , Yee Ti Teow , Kumarasinghe Gamini , Jamal Farida , Kamarulzaman Adeeba , Parasakthi Navaratnam , Van Pham Hung , Carlos Celia , So Thomas , Ng Tak Keung , Shibl Atef
Published: May 2004

A total of 685 clinical
Streptococcus pneumoniae
isolates from patients with pneumococcal diseases were collected from 14 centers in 11 Asian countries from January 2000 to June 2001. The in vitro susceptibilities of the isolates to 14 antimicrobial agents were determined by the broth microdilution test. Among the isolates tested, 483 (52.4%) were not susceptible to penicillin, 23% were intermediate, and 29.4% were penicillin resistant (MICs ≥ 2 mg/liter). Isolates from Vietnam showed the highest prevalence of penicillin resistance (71.4%), followed by those from Korea (54.8%), Hong Kong (43.2%), and Taiwan (38.6%). The penicillin MICs at which 90% of isolates are inhibited (MIC
90
s) were 4 mg/liter among isolates from Vietnam, Hong Kong, Korea, and Taiwan. The prevalence of erythromycin resistance was also very high in Vietnam (92.1%), Taiwan (86%), Korea (80.6%), Hong Kong (76.8%), and China (73.9%). The MIC
90
s of erythromycin were >32 mg/liter among isolates from Korea, Vietnam, China, Taiwan, Singapore, Malaysia, and Hong Kong. Isolates from Hong Kong showed the highest rate of ciprofloxacin resistance (11.8%), followed by isolates from Sri Lanka (9.5%), the Philippines (9.1%), and Korea (6.5%). Multilocus sequence typing showed that the spread of the Taiwan
19F
clone and the Spain
23F
clone could be one of the major reasons for the rapid increases in antimicrobial resistance among
S. pneumoniae
isolates in Asia. Data from the multinational surveillance study clearly documented distinctive increases in the prevalence rates and the levels of antimicrobial resistance among
S. pneumoniae
isolates in many Asian countries, which are among the highest in the world published to date.
Efficacy of Oral Ramoplanin for Inhibition of Intestinal Colonization by Vancomycin-Resistant Enterococci in Mice
Authors: Stiefel Usha , Pultz Nicole J. , Helfand Marion S. , Donskey Curtis J.
Published: May 2004

Ramoplanin is a glycolipodepsipeptide antibiotic with activity against gram-positive bacteria that is in clinical trials for prevention of vancomycin-resistant
Enterococcus
(VRE) bloodstream infections and treatment of
Clostridium difficile
diarrhea. Orally administered ramoplanin suppresses VRE intestinal colonization, but recurrences after discontinuation of treatment have frequently been observed. We used a mouse model to examine the efficacy of ramoplanin for inhibition of VRE colonization and evaluated the etiology of recurrences of colonization. Eight days of treatment with ramoplanin (100 μg/ml) in drinking water suppressed VRE to undetectable levels, but 100% of mice developed recurrent colonization; a higher dose of 500 μg/ml in water was associated with recurrent colonization in 50% of mice. Two of eight (25%) mice treated with the 100-μg/ml dose of ramoplanin had low levels of VRE in their cecal tissues on day 8 despite undetectable levels in stool and cecal contents. Mice that received prior ramoplanin treatment did not develop VRE overgrowth when challenged with 10
7
CFU of oral VRE 1, 2, or 4 days later. In communal cages, rapid cross-transmission and overgrowth of VRE was observed among clindamycin-treated mice; ramoplanin treatment effectively suppressed VRE overgrowth in such communal cages. Ramoplanin treatment promoted increased density of indigenous
Enterobacteriaceae
and overgrowth of an exogenously administered
Klebsiella pneumoniae
isolate. These results demonstrate the efficacy of ramoplanin for inhibition of VRE colonization and suggest that some recurrences occur due to reexpansion of organisms that persist within the lining of the colon. Ramoplanin treatment may be associated with overgrowth of gram-negative bacilli.
Structure and Association of Human Lactoferrin Peptides withEscherichia coliLipopolysaccharide
Authors: Chapple Daniel S. , Hussain Rohanah , Joannou Christopher L. , Hancock Robert E. W. , Odell Edward , Evans Robert W. , Siligardi Giuliano
Published: May 2004

An 11-amino-acid amphipathic synthetic peptide homologous to a helical region on helix 1 of human lactoferrin HLP-2 exhibited bactericidal activity againstEscherichia coliserotype O111, whereas an analogue synthesized with Pro substituted for Met, HLP-6, had greatly reduced antimicrobial activity. The bactericidal activity of HLP-2 was 10-fold greater than that of HLP-6 in both buffer and growth medium by time-kill assays. These assays also showed a pronounced lag phase that was both concentration and time dependent and that was far greater for HLP-2 than for HLP-6. Both peptides, however, were shown to be equally efficient in destabilizing the outer membrane when the hydrophobic probe 1-N-phenylnaphthylamine was used and to have the same lipopolysaccharide (LPS) binding affinity, as shown by polymyxin B displacement. Circular dichroism (CD) spectroscopy was used to study the structure and the organization of the peptides in solution and upon interaction withE. coliLPS. In the presence of LPS, HLP-2 and HLP-6 were found to bind and adopt a β-strand conformation rather than an α-helix, as shown by nonimmobilized ligand interaction assay-CD spectroscopy. Furthermore, this assay was used to show that there is a time-dependent association of peptide that results in an ordered formation of peptide aggregates. The rate of interpeptide association was far greater in HLP-2 LPS than in HLP-6 LPS, which was consistent with the lag phase observed on the killing curves. These results allow us to propose a mechanism by which HLP-2 folds and self-assembles at the outer membrane surface before exerting its activity.
Phosphorothioate Di- and Trinucleotides as a Novel Class of Anti-Hepatitis B Virus Agents
Authors: Iyer Radhakrishnan P. , Jin Yi , Roland Arlene , Morrey John D. , Mounir Samir , Korba Brent
Published: May 2004

Several nucleoside analogs are under clinical development for use against hepatitis B virus (HBV). Lamivudine (3TC), a nucleoside analog, and adefovir dipivoxil (ADV), an acyclonucleotide analog, are clinically approved. However, long-term treatment can induce viral resistance, and following the cessation of therapy, viral rebound is frequently observed. There continues to be a need for new antiviral agents with novel mechanisms of action. A library of more than 600 di- and trinucleotide compounds synthesized by parallel synthesis using a combinatorial strategy was screened for potential inhibitors of HBV replication using the chronically HBV-producing cell line 2.2.15. Through an iterative process of synthesis, lead optimization, and screening, three analogs were identified as potent inhibitors of HBV replication: dinucleotides ORI-7246 (drug concentration at which a 10-fold reduction of HBV DNA was observed [EC
90
], 1.4 μM) and ORI-9020 (EC
90
, 1.2 μM) and trinucleotide ORI-7170 (EC
90
, 7.2 μM). These analogs inhibited the replication of both strands of HBV DNA. No suppression of HBV protein synthesis or intracellular core particle formation by these analogs was observed. No inhibition of HBV DNA strand elongation by the analogs or their 5′-triphosphate versions was apparent in in vitro polymerase assays. Although the exact mechanism of action is not yet identified, present data are consistent with an inhibition of the HBV reverse transcriptase-directed priming step prior to elongation of the first viral DNA strand. In transient-transfection assays, these analogs inhibited the replication of 3TC-resistant HBV. Synergistic interactions in combination treatments between the analogs and either 3TC or ADV were observed. These compounds represent a novel class of anti-HBV molecules and warrant further investigation as potential therapeutic agents.
Penetration of Meropenem into Pneumonic Human Lung Tissue as Measured by In Vivo Microdialysis
Authors: Tomaselli Florian , Maier Alfred , Matzi Veronika , Smolle-Jüttner Freyja Maria , Dittrich Peter
Published: May 2004

Until recently, information on antibiotic pharmacokinetic properties in infected human lung tissue was limited. We therefore studied a microdialysis-based approach for measurement of the penetration of meropenem into the extracellular space fluid of human pneumonic lung parenchyma. The lung penetration of meropenem was determined for seven patients with pneumonia and metapneumonic pleural empyema treated by decortication. Intraoperatively, two microdialysis probes were inserted into pneumonic lung tissue and one was inserted into healthy skeletal muscle for reference values. Serum and microdialysis samples were collected at 20-min intervals for at least 8 h following a single intravenous dose of 1 g of meropenem. The maximum free interstitial concentration (mean and standard deviation) of meropenem in infected lung tissue was 11.4 ± 10.9 mg/liter, and that in serum was 47.3 ± 21.0 mg/liter. The areas under the curve for infected lung tissue (36.2 ± 17.9 mg · h/liter) and serum (95.4 ± 46.6 mg · h/liter) revealed a significant difference. This technique enabled quasi-continuous tissue pharmacokinetic measurements of free, unbound antibiotic in pneumonic lung tissue of patients with pneumonia. The present data corroborate the use of meropenem in the treatment of lung infections caused by extracellular bacteria, demonstrating the excellent distribution profile for meropenem in the interstitial space of human pneumonic lung tissue.
Effect of Erythromycin on Chronic Respiratory Infection Caused byPseudomonas aeruginosawith Biofilm Formation in an Experimental Murine Model
Authors: Nagata Towako , Mukae Hiroshi , Kadota Junichi , Hayashi Tomayoshi , Fujii Takeshi , Kuroki Misuzu , Shirai Ryo , Yanagihara Katsunori , Tomono Kazunori , Koji Takehiko , Kohno Shigeru
Published: May 2004

Diffuse panbronchiolitis (DPB) is a chronic lower respiratory tract infection commonly associated with persistent late-stagePseudomonas aeruginosainfection. However, low-dose long-term therapy with certain macrolides is effective in most patients with DPB. The present study was designed to examine the effects of long-term erythromycin (ERY) therapy by using our established murine model of chronic respiratoryP. aeruginosainfection. ERY or saline was administered from day 80 after intubation with aP. aeruginosa-precoated tube for the subsequent 10, 20, 40, and 80 days. Bacteriologic and histologic analyses of the murine lungs and electron microscopy of the intubated tube were performed. In the murine model, treatment with ERY for 80 days significantly reduced the number of viableP. aeruginosaorganisms in the lungs (P< 0.05). The biofilm formed in situ byP. aeruginosaon the inner wall of the inoculation tube placed into the murine bronchus became significantly thinner after 80 days of ERY treatment. We conclude that the clinical efficacy of macrolides in DPB may be due at least in part to the reduction inP. aeruginosabiofilm formation.
Noninvasive Optical Imaging Method To Evaluate Postantibiotic Effects on Biofilm Infection In Vivo
Authors: Kadurugamuwa Jagath L. , Sin Lin V. , Yu Jun , Francis Kevin P. , Purchio Tony F. , Contag Pamela R.
Published: May 2004

Eradication of
Staphylococcus aureus
biofilms after rifampin treatment was tested in a mouse model of device-related infection by using biophotonic imaging. Following treatment, the bioluminescent signals decreased to undetectable levels, irrespective of the age of the biofilm. After the final treatment, the signals rebounded in a time-dependent manner and reached those for the untreated mice. Readministration of rifampin was unsuccessful in eradicating reestablished infections, with the rifampin MICs for such bacteria being increased and with the bacteria having point mutations in the
rpoB
gene.
Salmonella
Gene
rma
(
ramA
) and Multiple-Drug-Resistant
Salmonella enterica
Serovar Typhimurium
Authors: van der Straaten Tahar , Janssen Riny , Mevius Dik J. , van Dissel Jaap T.
Published: May 2004

MarA and its homologue, RamA, have been implicated in multidrug resistance (MDR).
RamA
overexpression in
Salmonella enterica
serovar Typhimurium and
Escherichia coli
conferred MDR independently of
marA
. Inactivation of
ramA
did not affect the antibiotic susceptibilities of wild-type
S. enterica
serovar Typhimurium or 15 unrelated clinical MDR isolates. Thus,
ramA
overexpression is not a common MDR mechanism in
Salmonella
.
Fitness Cost of SCC
mec
and Methicillin Resistance Levels in
Staphylococcus aureus
Authors: Ender Miriam , McCallum Nadine , Adhikari Rajan , Berger-Bächi Brigitte
Published: May 2004

Transformation of a type I SCC
mec
element into
Staphylococcus aureus
yielded highly oxacillin-resistant transformants with a reduced growth rate. Faster-growing variants could again be selected at the cost of reduced resistance levels, demonstrating an inverse correlation between oxacillin resistance levels and growth rate.
In Vitro Effects of Albendazole Sulfoxide and Praziquantel against
Taenia solium
and
Taenia crassiceps
Cysts
Authors: Palomares Francisca , Palencia Guadalupe , Pérez Rodolfo , González-Esquivel Dinora , Castro Nelly , Cook Helgi Jung
Published: May 2004

We investigated the minimum exposure times of prazicuantel (PZQ) and albendazole sulfoxide (ABZSO) required for their activities against
Taenia
cysts in vitro as well as the 50 and 99% effective concentrations. The results showed that although the effects of both drugs are time and concentration dependent, ABZSO acts much slower and is less potent than PZQ.
High-Level Resistance to Ceftazidime Conferred by a Novel Enzyme, CTX-M-32, Derived from CTX-M-1 through a Single Asp240-Gly Substitution
Authors: Cartelle Monica , del Mar Tomas Maria , Molina Francisca , Moure Rita , Villanueva Rosa , Bou German
Published: May 2004

A clinical strain of
Escherichia coli
isolated from pleural liquid with high levels of resistance to cefotaxime, ceftazidime, and aztreonam harbors a novel CTX-M gene (
bla
CTX-M-32
) whose amino acid sequence differs from that of CTX-M-1 by a single Asp240-Gly substitution. Moreover, by site-directed mutagenesis we demonstrated that this replacement is a key event in ceftazidime hydrolysis
Molecular Characterization of a Carbapenem-Hydrolyzing Class A β-Lactamase, SFC-1, from
Serratia fonticola
UTAD54
Authors: Henriques Isabel , Moura Alexandra , Alves Artur , Saavedra Maria José , Correia António
Published: May 2004

An environmental isolate of
Serratia fonticola
resistant to carbapenems contains a gene encoding a class A β-lactamase with carbapenemase activity. The enzyme was designated SFC-1. The
bla
SFC-I
gene is contained in the chromosome of
S. fonticola
UTAD54 and is absent from other
S. fonticola
strains.
Potential New Anti-Human Immunodeficiency Virus Type 1 Compounds Depress Virus Replication in Cultured Human Macrophages
Authors: Ewart Gary D. , Nasr Najla , Naif Hassan , Cox Graeme B. , Cunningham Anthony L. , Gage Peter W.
Published: May 2004

We report that the amiloride analogues 5-(
N
,
N
-hexamethylene)amiloride and 5-(
N
,
N
-dimethyl)amiloride inhibit, at micromolar concentrations, the replication of human immunodeficiency virus type 1 (HIV-1) in cultured human blood monocyte-derived macrophages. These compounds also inhibit the in vitro activities of the HIV-1 Vpu protein and might represent lead compounds for a new class of anti-HIV-1 drugs.
Effect of trail design and grooming on the incidence of injuries at alpine ski areas
Authors: Bergstrøm K A , Ekeland A
Published: May 2004

Objectives:To identify the conditions at certain sites on slopes known as black spots for injury.

Method:In the Hafjell and Voss alpine ski areas in Norway, 1410 skiing injuries were recorded from December 1990 through the 1996 season. In Hafjell, 183 of these injuries were plotted on an area map during the two first seasons. Similarly, in Voss, 214 injuries were plotted on an area map for two seasons. During the last three seasons in Hafjell, 835 ski injuries were related to 6712 snow grooming hours and 6 829 084 lift journeys.

Results:The mean injury rate was 2.2 injuries per 1000 skier days, and the mean injury severity score (ISS) was 3.1. Accumulations of injuries at three sites (black spots) were recorded on the Hafjell area map. These injuries represented 40% of all injuries in the alpine area (p<0.05). Seven injury accumulation sites were recorded on the alpine area map of Voss, representing 22% of the total injuries (p>0.05). Grooming of the slopes was rated poor for the 49% of injuries that occurred at the sites of injury concentration and significantly different (27%) from injuries that occurred at random in Hafjell. The corresponding values in Voss were 50% and 25% respectively. Grooming hours appeared to be inversely proportional to the number of injuries:R =  −0.99 (p<0.02). The mean ISS declined significantly in Hafjell over the observation period (p<0.001).

Conclusion:Inappropriate trail design and slope grooming seem to result in an accumulation of injuries at certain sites. Modification in construction and maintenance of the courses may reduce the number of injuries and mean ISS.
Role of a mixed type, moderate intensity exercise programme after peripheral blood stem cell transplantation
Authors: Hayes S C , Davies P S , Parker T W , Bashford J , Green A
Published: May 2004

Objectives:To evaluate the effect of peripheral blood stem cell transplantation on functional capacity, and to determine the role of a mixed type, moderate intensity exercise programme in the recovery of patients after intensive cancer treatment.

Methods:Peak aerobic capacity and muscular strength (upper body, lower body, and handgrip strength) measures were assessed before (PI) and after (PII) transplant and after a 12 week intervention period (PIII). After PII, 12 patients aged 16–64 years were allotted in equal numbers to a control group or exercise intervention group.

Results:Mean peak aerobic capacity and muscular strength were reduced after the transplant, with significant (p<0.05) decreases for upper body strength. No change was found in aerobic capacity and muscular strength between PII and PIII for the control group. In contrast, participation in the exercise programme led to significant improvements in peak aerobic capacity (p<0.05) and upper and lower body strength (p<0.01). In addition, values recorded after the three month intervention period were significantly higher than before treatment for peak aerobic capacity (litres/min (p<0.05) and ml/kg/min (p<0.01)) and lower body strength (p<0.01).

Conclusion:Intensive treatment for cancer can adversely affect aerobic capacity and muscular strength. A mixed type, moderate intensity exercise programme can help patients to regain fitness and strength within three months. No exercise can exacerbate physical losses resulting from treatment.
Diclofenac patch for topical treatment of acute impact injuries: a randomised, double blind, placebo controlled, multicentre study
Authors: Predel H G , Koll R , Pabst H , Dieter R , Gallacchi G , Giannetti B , Bulitta M , Heidecker J L , Mueller E A
Published: May 2004

Objectives:To investigate the clinical efficacy and safety of a newly developed diclofenac patch in the topical treatment of blunt impact injuries.

Methods:This was a randomised, placebo controlled, double blind, multicentre study in 120 patients with traumatic blunt soft tissue injury. Within 3 h of the injury participants of sport competitions and training camps were enrolled and treated twice daily with the diclofenac or a placebo patch over a period of 7 days. Patients were randomised (1:1) to two parallel groups. Tenderness produced by pressure was measured twice daily during the first 3 days after enrolment as well as at day 7. Tenderness was defined as the amount of pressure (measured by a calibrated caliper at the centre of the injury) that first produced a pain reaction as reported by the patient.

Results:The primary efficacy variable was the area under the curve for tenderness over the first 3 days. The diclofenac patch was significantly more effective than placebo (p<0.0001). The treatment effect was 64.7 kp h/cm2(95% confidence interval 48.7 to 80.9) between diclofenac and placebo patches. These results were supported by all secondary efficacy variables. The diclofenac patch produced rapid pain relief as reflected by the time to reach resolution of pain at the injured site which was significantly shorter compared to placebo (p<0.0001). The diclofenac patch was well tolerated. The most frequently observed adverse events were local cutaneous adverse reactions (pruritus, rash) of minor severity occurring with the same frequency as in the placebo group.

Conclusions:A newly developed diclofenac patch is effective and safe for the treatment of blunt impact injuries.
What do we mean by the term “inflammation”? A contemporary basic science update for sports medicine
Authors: Scott A , Khan K M , Roberts C R , Cook J L , Duronio V
Published: May 2004

Most practicing sports medicine clinicians refer to the concept of “inflammation” many times a day when diagnosing and treating acute and overuse injuries. What is meant by this term? Is it a “good” or a “bad” process? The major advances in the understanding of inflammation in recent years are summarised, and some clinical implications of the contemporary model of inflammation are highlighted.