bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous ventilation with remifentanil in children
Authors: Ansermino J Mark , Brooks Peter , Rosen David , A Vandebeek Christine , Reichert Clayton
Published: January 2005

Background : Remifentanil is a short‐acting drug that allows us to study the specific respiratory effects of potent opioid analgesics. The purpose of this study is to describe the effects of a remifentanil infusion during spontaneous ventilation in children. Pharmacokinetic studies provide useful information on the time course of opioid blood concentrations; however, they cannot be easily translated into infusion administration guidelines for pediatric clinical practice.

Methods : A total of 32 children, aged 2–7 years, undergoing restorative dentistry, spontaneously breathing under sevoflurane anesthesia were enrolled in the study. After an initial bolus dose of remifentanil, an infusion was administered in ascending logarithmic increments at 10 min intervals. Increments were discontinued when endtidal carbon dioxide exceeded 9 kPa (70 mmHg), desaturation occurred (SpO2 < 94%) or with the onset of apnea (>5 s). The maximum tolerated dose was determined for each subject. Endtidal carbon dioxide, minute ventilation and respiratory rate were continuously recorded.

Results : The median tolerated dose of remifentanil was 0.127μg·kg−1·min−1 (range: 0.053–0.3 μg·kg−1·min−1). When comparing the last four incremental increases in each subject, 35% change in respiratory rate occurred in the last 10 min period while changes in endtidal carbon dioxide and minute ventilation were gradual and of less magnitude. There was no correlation between age and respiratory rate.

Conclusions : There is a large variation in the dose of remifentanil tolerated by children while breathing spontaneously under anesthesia. A respiratory rate of <10 b·min−1 appears to be the best predictor of the maximum tolerated dose.
Distorted perception of smell by volatile agents facilitated inhalational induction of anesthesia
Authors: FUKUMOTO MASATOSHI , ARIMA HAJIME , ITO SARI , TAKEUCHI NAOKO , NAKANO HIROSHI
Published: January 2005

Background:  Unpleasant smell of halogenated volatile agents is one of the frustrating factors for inhalational induction. We developed a new modification that might enable children to enjoy the smell itself while incrementally elevating sevoflurane concentration. Troposmia is usually a pathological quality change of smell perception and an olfactory stimulus is distortedly perceived in this state, which we applied to inhalational induction.

Methods:  At the preoperative visit an anesthetist told the children that the smell of a facemask could be magically changed from strawberry into anything and promised to change the smell as they requested. In the operating room, a strawberry scented facemask was fitted to the face and the anesthetist announced to them that the magical change of the smell would begin when sevoflurane was added. Whether children perceived the change of the smell as they requested was investigated in the troposmia group, and resistance to fit a facemask was compared between the troposmia group and a control group.

Results:  Significantly fewer children resisted the facemask in the troposmia group (1 of 32 Vs 9 of 32; P = 0.0059). In the troposmia group 18, 22 and 25 of the 32 children said the smell of the facemask changed as they requested before they fell asleep, at the postoperative visit or both, respectively.

Conclusions:  Troposmia can be intentionally induced to perceive the smell of sevoflurane on request. Troposmia might contribute to promote children's participation in anesthesia induction and facilitate inhalational induction.
The Portex ‘Soft Seal’ single use laryngeal mask – a preliminary study in pediatric anesthesia
Authors: GLAISYER HILARY R. , YULE C.
Published: January 2005

Background:  Portex have developed a single use pediatric laryngeal mask (LM), which is available in all sizes.

Methods:  We prospectively evaluated its use in 40 infants and children undergoing a variety of surgical procedures.

Results:  The LM provided a satisfactory airway in all patients. Insertion was quick and easy and achieved at the first attempt in 38 patients. Repositioning was required during anesthesia in four cases.

Conclusions:  The Portex ‘Soft Seal’ LM performs satisfactorily in elective pediatric anesthesia.
Prevalence and characteristics of screen‐detected prostate carcinomas at low prostate‐specific antigen levels: aggressive or insignificant?
Authors: Gosselaar Claartje , Roobol Monique J. , Schröder Fritz H.
Published: January 2005

Screening for prostate cancer at low prostate‐specific antigen (PSA) levels (≤4.0 ng/mL) risks detecting clinically insignificant cancers, which are of no threat to the man. In this review we evaluate the prevalence and tumour characteristics of prostate cancer detected at low PSA levels, comparing screening studies, cystoprostatectomy series and autopsy data. The favourable characteristics of tumours detectable at very low PSA levels seem to justify the conclusion that an unknown but sizeable proportion of the cancers found at biopsy are clinically insignificant.
Internalism and Externalism in Ethics Applied to the Liberal-Communitarian Debate
Authors: Dimova-Cookson Maria
Published: January 2005

This article addresses the question of whether we can explain moral action in terms of an attraction to a moral ideal. It defends T. H. Green's internalist ethics against John Skorupski's externalist claim that moral ideals are optional whereas moral duties are not. A parallel is drawn between the Internalism and Externalism debate in ethics and the liberal-communitarian debate in political theory. My defence of Internalism offers new arguments in support of communitarian approaches to the nature of moral action. Green's internalist ethics provides the communitarian discourse with the universalist moral dimension it traditionally lacks.
Variable Names and Constant Names in Wittgenstein's Tractatus
Authors: Cheung Leo K. C.
Published: January 2005

In this paper, I argue that the Tractatus classifies names into constant names and variable names. A variable name, via the application of the existential quantifier against the background of picturing, picks out and denotes an unspecified object from the range of objects of the form shown by the relevant variable. A constant name labels an object picked out from a scope of the existential quantifier. I also refute two types of attempts to argue that the Tractarian relation between a name and its meaning is not realist, and to explain why it is more reasonable to hold that it is.
The Voices of Wittgenstein: The Vienna Circle
Authors: Stock Guy
Published: January 2005

Book reviewed:

The Voices of Wittgenstein: The Vienna Circle– Ludwig Wittgenstein and Friedrich Waismann (Transcribed, Edited and with an Introduction by Gordon Baker; Translated by Gordon Baker, Michael Mackett, John Connolly and Vasilis Politis); Routledge; London and New York, 2003 (Pp xlviii + 558. German and English Texts on Facing Pages.)
Oppression and Responsibility: a Wittgensteinian Approach to Social Practices and Moral Theory
Authors: Johnson Paul F
Published: January 2005

Book reviewed:

O’Connor, Peg, Oppression and Responsibility: a Wittgensteinian Approach to Social Practices and Moral Theory, The Pennsylvania State University Press, 2002, 151 pp., ISBN 0‐271‐02202‐7.
Indinavir/ritonavir‐based therapy in HIV‐1‐infected antiretroviral therapy‐naive patients: comparison of 800/100 mg and 400/100 mg twice daily
Authors: Konopnicki D , De Wit S , Poll B , Crommentuyn K , Huitema A , Clumeck N
Published: January 2005

Objectives

To compare the efficacy and tolerability of indinavir (IDV)/ritonavir (RTV) at 800/100 and 400/100 mg twice daily (bid) in antiretroviral therapy (ART)‐naive patients.

Methods

An open comparison of two groups of ART‐naive patients treated with IDV/RTV 800/100 or 400/100 mg bid plus two nucleoside analogues was carried out. Viral load, CD4 cell count and tolerability were measured at baseline and at weeks 4, 12, 24 and 48. IDV plasma concentrations were measured retrospectively.

Results

A total of 107 patients were included in the study. Of these, 57 were treated with 800/100 and 50 with 400/100 mg IDV/RTV bid. At week 48, a viral load of <50 HIV‐1 RNA copies/mL was achieved by 77 and 64% of the patients, respectively, and the median CD4 cell count increases were +171 and +164 cells/μL (intent‐to‐treat; P not significant), respectively. Side effects leading to protease inhibitor discontinuation occurred in 61% of subjects in the 800/100 mg group vs. 20% in the 400/100 mg group (P<0.0001). Switching from 800/100 to 400/100 mg dosage improved adverse events in 16 of 20 patients. IDV concentrations were above 0.15 mg/L in 89% of the 28 patients tested in the 400/100 mg group.

Conclusions

Indinavir/ritonavir 400/100 mg bid provided the same efficacy as 800/100 mg bid at 48 weeks in an ART‐naive population, but safety and tolerance were significantly better for 400/100 mg, while convenience was also improved and cost was reduced.
Coronary artery bypass grafting in a patient with HIV
Authors: Bethuyne N , Lacor P , Goldstein JP , Deuvaert FE
Published: January 2005

We report a successful case of a conventional coronary artery bypass operation performed in a patient with HIV infection and severe three‐vessel coronary artery disease. The signal change in outcome of HIV disease, in addition to the reported evidence for accelerated atherosclerosis caused by the disease itself and by its treatment with protease inhibitors, is likely to produce a larger population of HIV‐infected patients developing premature coronary artery disease for whom cardiac surgery will be required. Surgical risk, outcome and operative team risk are discussed.
Hydroxychloroquine, hydroxyurea and didanosine as initial therapy for HIV‐infected patients with low viral load: safety, efficacy and resistance profile after 144 weeks
Authors: Paton NI , Aboulhab J
Published: January 2005

Objectives

To evaluate the long‐term safety and efficacy of the combination of hydroxychloroquine, hydroxyurea and didanosine.

Methods

We recruited antiretroviral‐naive patients with viral loads less than 100 000 HIV‐1 RNA copies/mL and CD4 counts greater than 150 cells/μL. All patients received hydroxychloroquine (200 mg), hydroxyurea (500 mg) and didanosine (125–200 mg) twice daily. Clinical and laboratory safety assessments and measurements of viral load and CD4 count were made at regular intervals, and genotypic resistance testing was performed on samples with detectable viral load at 48, 96 and 144 weeks.

Results

Fourteen of the 17 patients who commenced therapy remained on treatment at 144 weeks. Treatment was well tolerated but caused neutropenia, usually mild and transient, in 12 patients (71%). Mean viral load was reduced by 1.6 log10 copies/mL below baseline (P<0.001), eight patients (47%) had undetectable viral load (<400 copies/mL), and two patients (12%) had detectable viral load but no detectable resistance mutations at week 144. Four patients (24%) had detectable viral load together with major resistance mutations (three with both 74 V and 184 V, and one with both 62 V and 65R) at week 144, but still had viral load suppression below baseline. Mean CD4 count was increased by 106 cells/μL above baseline (P=0.07) at week 144.

Conclusions

This novel and well‐tolerated combination controls viral replication during long‐term follow up, with development of few resistance mutations. With careful monitoring it may be a useful strategy for delaying highly active antiretroviral therapy (HAART) and associated toxicity in selected patients with low initial viral loads.
Pancreatic exocrine insufficiency in HIV‐positive patients
Authors: Price DA , Schmid ML , Ong ELC , Adjukeiwicz KMB , Peaston B , Snow MH
Published: January 2005

Objectives

We describe the management of a cohort of eight HIV‐positive patients on antiretroviral medication with evidence of pancreatic insufficiency consisting of chronic diarrhoea and a low faecal elastase measurement.

Patients and methods

Twenty‐two patients with chronic diarrhoea for whom a faecal elastase measurement was available were identified retrospectively. We compared baseline demographic characteristics, antiretroviral treatment and symptoms of steatorrhea between patients with evidence of pancreatic insufficiency, i.e. a low faecal elastase measurement of <200 μg/g (cases), and patients with evidence of normal pancreatic function, i.e. a normal faecal elastase measurement of >200 μg/g (controls). We describe the management of the patients with evidence of pancreatic insufficiency.

Results

Of the 22 patients, eight had evidence of pancreatic insufficiency, i.e. a low faecal elastase measurement. Comparing cases with controls, cases were more likely to have symptoms of steatorrhea (P=0.03) or to have lost weight (P=0.02). Cases were also significantly more likely to have taken didanosine (ddI) as part of their antiretroviral treatment when their symptoms started. Seven cases were treated with oral pancreatic supplements and all had symptomatic improvement of their diarrhoea. One patient stopped treatment with oral pancreatic supplements because of side effects without a relapse of symptoms; he had also stopped zalcitabine (ddC).

Conclusions

We believe that measurement of faecal elastase to detect pancreatic insufficiency should be part of the standard investigation of HIV‐positive patients with chronic diarrhoea alongside assessment for other causes of diarrhoea. Faecal elastase measurements should be requested, in particular, in all patients with diarrhoea and weight loss, or symptoms of steatorrhea, and in those on treatment with an antiretroviral regime containing ddI. If the faecal elastase level is low, a switch of antiretroviral medication to a nonddI/ddC‐containing regime should be considered and treatment with oral pancreatic enzyme therapy should be instituted.
Diastasis recti abdominis in HIV‐infected men with lipodystrophy
Authors: Blanchard PD
Published: January 2005

Diastasis recti abdominis is a condition in which the rectus abdominus muscle separates in the midline at the linea alba producing a ventral herniation. We have observed the occurrence of this condition in HIV‐infected men attending an osteopathic clinic. Two such cases are described in detail. An apparent association with HIV‐associated lipodystrophy syndrome and implications for management are explored.
Study on Biocompatibility of Complexes of Collagen–Chitosan–Sodium Hyaluronate and Cornea
Authors: Chen Jiansu , Li Qinhua , Xu Jintang , Huang Yaoxiong , Ding Yong , Deng Hongwei , Zhao Songbin , Chen Rui
Published: January 2005

Abstract:  In this study we investigated the biocompatibility of collagen–chitosan–sodium hyaluronate (Col–Chi–NaHA) complexes and cornea tissue, and the feasibility of Col–Chi–NaHA complexes as substrates for cultivating rabbit corneal cells. Different components of Col–Chi–NaHA complexes were prepared and tested. A circular complex film with a diameter of 6 mm was inserted into rabbit stomal pocket and traced for a period of 5 months. Clinical examination was made. Rabbit limbal corneal epithelial cells, corneal endothelial cells, and keratocytes were cultured primarily on complexes. Phase contrast microscope examination was made daily. Histological, immunohistochemical, and scanning electron microscopic examinations were carried out. The complexes of 20% collagen, 10% chitosan, and 0.5% sodium hyaluronate showed rather weak corneal edema and other responses. The degradation of materials was obvious after 5 months. Corneas were transparent and translucent. Cells seeded on Col–Chi–NaHA were allowed to proliferate and partly form confluent monolayer after 9 days in culture. Cultured cells were well attached to the complexes of 20% collagen, 10% chitosan, and 0.5% sodium hyaluronate, or 10% chitosan and 0.5% sodium hyaluronate. The results showed that Col–Chi–NaHA complexes had good biocompatibility with cornea. The complexes can degrade and be absorbed in cornea. Col–Chi–NaHA complex may be a suitable substrate for cultivating corneal cells and a feasible material as a scaffold of tissue‐engineered cornea.
Proliferation Rates of HepG2 Cells Encapsulated in Alginate Are Increased in a Microgravity Environment Compared With Static Cultures
Authors: Coward Sam M. , Selden Clare , Mantalaris Athanasios , Hodgson Humphrey J.F.
Published: January 2005

Abstract:  This study investigates the effect of rotary culture compared with static culture on the proliferation, cell viability, synthetic function and detoxificatory capacity of HepG2 cells encapsulated in 1% alginate. Cell viability and alginate bead morphology were maintained in the rotary culture system at day 10, while cell number showed a 4.5‐fold increase compared with static culture. Protein production was increased in rotary cultures with a 4.1‐fold increase in total albumin and a 4.4‐fold increase in α1 antitrypsin levels in rotary compared with static culture at day 10. CYP4501A1/2 activity was maintained between the two culture systems. In conclusion, rotary culture increases proliferation rates leading to improved bead packing and a concomitant increase in total protein synthesis, along with maintenance of detoxificatory capacity. This allows a greater level of hepatic function to be expressed in a given volume, offering clear advantages for the design of liver support systems.
New Approaches to the Formation of a Stationary Phase in an Immunoadsorption Wall
Authors: Yang Tsung‐Hua
Published: January 2005

Abstract:  The concept of an immunoadsorption wall, which combines the principles of immunoisolation and immunoadsorption, was proposed in 1999 to remove certain toxins accumulated in patients’ blood. However, realization of this concept is obviously handicapped by the inefficient use of immunoadsorbent. This study is intended to improve the use of immunoadsorbent and optimize the formation of a stationary phase in an immunoadsorption wall. Polyacrylamide gel, which has the advantages of being chemically inert, having minimal diffusion effect and reasonable cost, could be considered as the medium of choice for a stationary phase. In this study, new approaches aimed at effective allocation of immunoadsorbent utilizing polyacrylamide gel are attempted. The advantages and disadvantages of these new approaches are discussed according to the preparation, formation, and outcome of a stationary phase. It is hoped that these new approaches could serve as a first step toward building an immunoadsorption wall.
Bridging the Workforce Gap for Our Aging Society: How to Increase and Improve Knowledge and Training. Report of an Expert Panel
Authors: LaMascus Alice Mankin , Bernard Marie A. , Barry Patricia , Salerno Judith , Weiss Joan
Published: January 2005

The healthcare workforce is currently unprepared for the increasing number of older persons and the complexities of their healthcare needs. Too few healthcare workers are adequately trained in geriatrics, and developers of educational curricula across healthcare disciplines have been slow to incorporate or require geriatric training. In April 2003, leaders in geriatrics met in Washington, D.C., to discuss and recommend solutions to the growing shortage of an appropriately trained workforce for geriatric research, education, and patient care. After considering data, presenting statistics, and offering insights into the future, the conference concluded by formulating recommendations to meet specific challenges. This report is a summary of the conference proceedings and recommendations, and it serves as a reminder that demographic trends and an everexpanding geriatric knowledge base demand not only attention, but also action.
An Improved Cluster-Renewal Model for the Estimation of Heat Transfer Coefficients on the Furnace Walls of Commercial Circulating Fluidized Bed Boilers
Authors: Dutta Animesh , Basu Prabir
Published: January 2005

Using data from large CFB boilers, and taking average solids concentration, size and height of the boiler-furnace as variables, a correlation for fractional wall coverage has been developed. This correlation for wall coverage and several other refinements have been used to modify the cluster renewal model of heat transfer. Predicted heat transfer coefficients from this model, for a wide range of CFB boilers, show good agreements with those measured in these boilers.
Assessment of Periodic Flow Assumption for Unsteady Heat Transfer in Grooved Channels
Authors: Chung Yongmann M. , Tucker Paul G.
Published: January 2005

Numerical studies of unsteady heat transfer in grooved channel flows are made. The flows are of special relevance to electronic systems. Predictions suggest a commonly used periodic flow assumption (for modeling rows of similar electronic components) may not be valid over a significant system extent. It is found that the downstream flow development is strongly dependent on geometry.
Mutation of
tlyA
Confers Capreomycin Resistance in
Mycobacterium tuberculosis
Authors: Maus Courtney E. , Plikaytis Bonnie B. , Shinnick Thomas M.
Published: January 2005

Capreomycin, an important drug for the treatment of multidrug-resistant tuberculosis, is a macrocyclic peptide antibiotic produced by
Saccharothrix mutabolis
subspecies
capreolus
. The basis of resistance to this drug was investigated by isolating and characterizing capreomycin-resistant strains of
Mycobacterium smegmatis
and
Mycobacterium tuberculosis
. Colonies resistant to capreomycin were recovered from a library of transposon-mutagenized
M. smegmatis
. The transposon insertion site of one mutant was mapped to an open reading frame in the unfinished
M. smegmatis
genome corresponding to the
tlyA
gene (Rv1694) in the
M. tuberculosis
H37Rv genome. In
M. smegmatis
spontaneous capreomycin-resistant mutants, the
tlyA
gene was disrupted by one of three different naturally occurring insertion elements. Genomic DNAs from pools of transposon mutants of
M. tuberculosis
H37Rv were screened by PCR by using primers to the
tlyA
gene and the transposon to detect mutants with an insertion in the
tlyA
gen
e
. One capreomycin-resistant mutant was recovered that contained the transposon inserted at base 644 of the
tlyA
gene. Complementation with the wild-type
tlyA
gene restored susceptibility to capreomycin in the
M. smegmatis
and
M. tuberculosis tlyA
transposon mutants. Mutations were found in the
tlyA
genes of 28 spontaneous capreomycin-resistant mutants generated from three different
M. tuberculosis
strains and in the
tlyA
genes of capreomycin-resistant clinical isolates. In in vitro transcription-translation assays, ribosomes from
tlyA
mutant but not
tlyA
+
strains resist capreomycin inhibition of transcription-translation. Therefore, TlyA appears to affect the ribosome, and mutation of
tlyA
confers capreomycin resistance.
Novel SHV-Derived Extended-Spectrum β-Lactamase, SHV-57, That Confers Resistance to Ceftazidime but Not Cefazolin
Authors: Ma Ling , Alba Jimena , Chang Feng-Yee , Ishiguro Masaji , Yamaguchi Keizo , Siu L. K. , Ishii Yoshikazu
Published: January 2005

A new SHV-derived extended-spectrum β-lactamase, SHV-57, that confers high-level resistance to ceftazidime but not cefotaxime or cefazolin was identified from a national surveillance study conducted in Taiwan in 1998. An
Escherichia coli
isolate resistant to ampicillin, cephalothin, and ceftazidime but sensitive to cefoxitin, ceftriaxone, cefotaxime, imipenem, and a narrow-spectrum cephem (cefazolin) was isolated from the urine of a patient treated with β-lactam antibiotics. Resistance to β-lactams was conjugatively transferred with a plasmid of about 50 kbp. The pI of this enzyme was 8.3. The sequence of the gene was determined, and the open reading frame of the gene was found to consist of 861 bases (GenBank accession number
AY223863
). Kinetic parameters showed that SHV-57 had a poor affinity to cefazolin. The

K
m

value toward cefazolin (5.57 × 10
3
μM) was extremely high in comparison to those toward ceftazidime (30.9 μM) and penicillin G (67 μM), indicating its low affinity to cefazolin. Although the

K
m

value of the β-lactamase inhibitor was too high for the study of catalytic activity (
k
cat
), indicating the low
k
cat
of SHV-57, the SHV-57 carrier was highly susceptible to a β-lactam-β-lactamase inhibitor combination. Comparison of the three-dimensional molecular model of SHV-57 with that of the SHV-1 β-lactamase suggests that the substitution of arginine for leucine-169 in the Ω loop is important for the substrate specificity.
Incidence and Mechanism of Ciprofloxacin Resistance in
Campylobacter
spp. Isolated from Commercial Poultry Flocks in the United Kingdom before, during, and after Fluoroquinolone Treatment
Authors: Griggs Deborah J. , Johnson Maggie M. , Frost Jennifer A. , Humphrey Tom , Jørgensen Frieda , Piddock Laura J. V.
Published: January 2005

Five commercial broiler flocks were treated with a fluoroquinolone for a clinically relevant infection. Fresh feces from individual chickens and environmental samples were cultured for campylobacters before, during, and weekly posttreatment until slaughter. Both
Campylobacter jejuni
and
C. coli
were isolated during all treatment phases. An increased proportion of quinolone-resistant strains was seen during treatment, and these strains persisted posttreatment. One quinolone-resistant isolate of each species, each serotype, and each phage type from each sample at all treatment phases was examined for its phenotype and mechanism of resistance. Two resistant phenotypes were isolated: Nal
r
Cip
r
and Nal
r
Cip
s
. The majority (269 of 290) of fluoroquinolone-resistant isolates, whether they were
C. jejuni
or
C. coli
, had a mutation in
gyrA
that resulted in the substitution Thr-86→Ile. The other
gyrA
mutations detected were Thr-86→Ala (
n
= 17) and Asp-90→Asn (
n
= 10). The genotypic variation, based on the silent mutations in
gyrA
identified by the denaturing high-performance liquid chromatography pattern and DNA sequencing, was used to supplement typing data and provided evidence for both the spread of preexisting resistant strains and the selection of spontaneous resistant mutants in treated flocks. Multidrug resistance was significantly (
P
< 0.01) associated with resistance to ciprofloxacin. Twenty-five percent (73 of 290) of ciprofloxacin-resistant isolates but only 13% (24 of 179) of susceptible isolates were resistant to three or more unrelated antimicrobial agents. In conclusion, quinolone-resistant campylobacters were isolated from commercial chicken flocks in high numbers following therapy with a veterinary fluoroquinolone. Most ciprofloxacin-resistant isolates had the GyrA substitution Thr-86→Ile. Resistant isolates were isolated from the feces of some flocks up to the point of slaughter, which may have consequences for public health.
Rapid Diffusion of Fluorescent Tracers into
Staphylococcus epidermidis
Biofilms Visualized by Time Lapse Microscopy
Authors: Rani Suriani Abdul , Pitts Betsey , Stewart Philip S.
Published: January 2005

The transient diffusion of fluorescent tracers into biofilm cell clusters of
Staphylococcus epidermidis
was visualized by time lapse confocal scanning laser microscopy. Rhodamine B diffused into the center of cell clusters that were 200 to 600 μm in diameter within a few minutes. The apparent effective diffusion coefficient calculated from these data averaged 3.7 × 10
−7
cm
2
s
−1
or 11% of the value in pure water. Fluorescein diffused into biofilm more rapidly, with a diffusion coefficient that averaged 1.6 × 10
−6
cm
2
s
−1
, or 32% of the value in water. This study provides direct, visual confirmation that solutes the size of many antibiotics and biocides can diffuse rapidly into biofilms.
Discovering the Mechanism of Action of Novel Antibacterial Agents through Transcriptional Profiling of Conditional Mutants
Authors: Freiberg C. , Fischer H. P. , Brunner N. A.
Published: January 2005

We present a new strategy for predicting novel antibiotic mechanisms of action based on the analysis of whole-genome microarray data. We first built up a reference compendium of
Bacillus subtilis
expression profiles induced by 14 different antibiotics. This data set was expanded by adding expression profiles from mutants that showed downregulation of genes coding for proven or emerging antibacterial targets. Here, we investigate conditional mutants underexpressing
ileS
,
pheST
,
fabF
, and
accDA
, each of which is essential for growth. Our proof-of-principle analyses reveal that conditional mutants can be used to mimic chemical inhibition of the corresponding gene products. Moreover, we show that a statistical data analysis combined with thorough pathway and regulon analysis can pinpoint the molecular target of uncharacterized antibiotics. We apply this approach to two novel antibiotics: a recently published phenyl-thiazolylurea derivative and the natural product moiramide B. Our results support recent findings suggesting that the phenyl-thiazolylurea derivative is a novel phenylalanyl-tRNA synthetase inhibitor. Finally, we propose a completely novel antibiotic mechanism of action for moiramide B based on inhibition of the bacterial acetyl coenzyme A carboxylase.
Bloodstream Infections Caused by Antibiotic-Resistant Gram-Negative Bacilli: Risk Factors for Mortality and Impact of Inappropriate Initial Antimicrobial Therapy on Outcome
Authors: Kang Cheol-In , Kim Sung-Han , Park Wan Beom , Lee Ki-Deok , Kim Hong-Bin , Kim Eui-Chong , Oh Myoung-don , Choe Kang-Won
Published: January 2005

The marked increase in the incidence of infections due to antibiotic-resistant gram-negative bacilli in recent years is of great concern, as patients infected by those isolates might initially receive antibiotics that are inactive against the responsible pathogens. To evaluate the effect of inappropriate initial antimicrobial therapy on survival, a total of 286 patients with antibiotic-resistant gram-negative bacteremia, 61 patients with
Escherichia coli
bacteremia, 65 with
Klebsiella pneumoniae
bacteremia, 74 with
Pseudomonas aeruginosa
bacteremia, and 86 with
Enterobacter
bacteremia, were analyzed retrospectively. If a patient received at least one antimicrobial agent to which the causative microorganisms were susceptible within 24 h of blood culture collection, the initial antimicrobial therapy was considered to have been appropriate. High-risk sources of bacteremia were defined as the lung, peritoneum, or an unknown source. The main outcome measure was 30-day mortality. Of the 286 patients, 135 (47.2%) received appropriate initial empirical antimicrobial therapy, and the remaining 151 (52.8%) patients received inappropriate therapy. The adequately treated group had a 27.4% mortality rate, whereas the inadequately treated group had a 38.4% mortality rate (
P
= 0.049). Multivariate analysis showed that the significant independent risk factors of mortality were presentation with septic shock, a high-risk source of bacteremia,
P. aeruginosa
infection, and an increasing APACHE II score. In the subgroup of patients (
n
= 132) with a high-risk source of bacteremia, inappropriate initial antimicrobial therapy was independently associated with increased mortality (odds ratio, 3.64; 95% confidence interval, 1.13 to 11.72;
P
= 0.030). Our data suggest that inappropriate initial antimicrobial therapy is associated with adverse outcome in antibiotic-resistant gram-negative bacteremia, particularly in patients with a high-risk source of bacteremia.
Antimicrobial Susceptibility Survey of
Streptococcus pyogenes
Isolated in Japan from Patients with Severe Invasive Group A Streptococcal Infections
Authors: Ikebe Tadayoshi , Hirasawa Kyoko , Suzuki Rieko , Isobe Junko , Tanaka Daisuke , Katsukawa Chihiro , Kawahara Ryuji , Tomita Masaaki , Ogata Kikuyo , Endoh Miyoko , Okuno Rumi , Watanabe Haruo
Published: January 2005

We assessed antimicrobial susceptibility against 211
Streptococcus pyogenes
strains isolated from patients with severe invasive group A streptococcal infections. Overall, 3.8, 1.4, 1.4, and 0.5% of the isolates were resistant to erythromycin, clindamycin, telithromycin, and ciprofloxacin, respectively, and 10.4% had intermediate resistance to ciprofloxacin. All isolates were susceptible to ampicillin and cefotaxime.
AcrAB Efflux Pump Plays a Role in Decreased Susceptibility to Tigecycline in
Morganella morganii
Authors: Ruzin Alexey , Keeney David , Bradford Patricia A.
Published: January 2005

Transposon mutagenesis of a clinical isolate of
Morganella morganii
, G1492 (tigecycline MIC of 4 μg/ml), yielded two insertion knockout mutants for which tigecycline MICs were 0.03 μg/ml. Transposon insertions mapped to
acrA
, which is constitutively overexpressed in G1492, suggesting a role of the AcrAB efflux pump in decreased susceptibility to tigecycline in
M. morganii
.
Test Characteristics of Perirectal and Rectal Swab Compared to Stool Sample for Detection of Fluoroquinolone-Resistant
Escherichia coli
in the Gastrointestinal Tract
Authors: Lautenbach Ebbing , Harris Anthony D. , Perencevich Eli N. , Nachamkin Irving , Tolomeo Pam , Metlay Joshua P.
Published: January 2005

Among 63 patients enrolled in a prospective cohort study of gut colonization with fluoroquinolone-resistant
Escherichia coli
, the sensitivity of perirectal swab compared to stool sample was 90% (95% confidence interval [CI], 70 to 99%) and the specificity was 100% (95% CI, 91 to 100%). For rectal swab, the sensitivity was 90% (95% CI, 68 to 99%) and the specificity was 100% (95% CI, 91 to 100%).
Cloning of a Novel Gene for Quinolone Resistance from a Transferable Plasmid in
Shigella flexneri
2b
Authors: Hata Mami , Suzuki Masahiro , Matsumoto Masakado , Takahashi Masao , Sato Katsuhiko , Ibe Shiro , Sakae Kenji
Published: January 2005

A novel gene for quinolone resistance was cloned from a transferable plasmid carried by a clinical isolate of
Shigella flexneri
2b that was resistant to fluoroquinolones. The plasmid conferred low-level resistance to quinolones on
Escherichia coli
HB101. The protein encoded by the gene showed 59% amino acid identity with Qnr.
Florfenicol-Chloramphenicol Exporter Gene
fexA
Is Part of the Novel Transposon Tn
558
Authors: Kehrenberg Corinna , Schwarz Stefan
Published: January 2005

The florfenicol-chloramphenicol exporter gene
fexA
is part of the novel transposon Tn
558
from
Staphylococcus lentus.
Similarities between Tn
558
and Tn
554
from
Staphylococcus aureus
included the arrangement of the transposase genes
tnpA
to -
C
and an
att554
-like target sequence. Circular forms of Tn
558
were detected and suggest the functional activity of this transposon.
In Vitro Activity of Telithromycin against Viridans Group Streptococci and
Streptococcus bovis
Isolated from Blood: Antimicrobial Susceptibility Patterns in Different Groups of Species
Authors: Rodríguez-Avial Iciar , Rodríguez-Avial Carmen , Culebras Esther , Picazo Juan J.
Published: January 2005

The in vitro activities of penicillin, erythromycin, clindamycin, and telithromycin were determined against 155 viridans group streptococci (VGS) and 18
Streptococcus bovis
blood isolates. Heterogeneity in the susceptibility patterns and macrolide resistance phenotypes and genotypes in the different groups of VGS was detected. We found seven telithromycin-resistant
S. bovis
isolates all harboring the
erm
(B) gene.
Extended-Spectrum β-Lactamases in
Escherichia coli
Isolated from Dogs and Cats in Rome, Italy, from 2001 to 2003
Authors: Carattoli Alessandra , Lovari Sarah , Franco Alessia , Cordaro Gessica , Di Matteo Paola , Battisti Antonio
Published: January 2005

We report expanded-spectrum cephalosporin resistance in
Escherichia coli
from dogs and cats in Rome, Italy. Three major β-lactamases (CMY-2, SHV-12, and CTX-M-1) are reported for the first time in
E. coli
from sick and healthy dogs and cats. Molecular characterization suggests the presence of several combinations of β-lactamase genes in
E. coli
from companion animals.
A fossil record of colonization and response of lacustrine fish populations to climate change
Authors: Newbrey Michael G , Ashworth Allan C
Published: January 2005

To study fish species colonization and the response of populations to climate change, we reexamined a well-preserved late Pleistocene to early Holocene fossil fish assemblage from lake deposits on the Missouri Coteau, North Dakota. The fossil fishes in the assemblage include complete specimens of yellow perch (Perca flavescens), brassy minnow (Hybognathus hankinsoni), blacknose shiner (Notropis heterolepis), banded killifish (Fundulus diaphanus), and brook stickleback (Culaea inconstans). The sequence of colonization is explained by individual thermal and relative water velocity tolerances for each species. There are six peaks in fish abundance during approximately 1000 years, indicating a response to environmental perturbations. Charcoal deposition from fires is inferred to represent episodic droughts during which nutrient levels were reduced and fish abundance declined. The fluctuations follow an overall trend of increased fish abundance during a time when lake-marginal vegetation changed from a spruce to a deciduous forest in response to climatic warming. This study provides insight into the complex effects of a changing climate on fish populations and demonstrates the potential of using fossils to examine the long-term abundance patterns of contemporary fish species.
Multivariate analysis of stable-isotope ratios to infer movements and utilization of estuarine organic matter by juvenile weakfish (Cynoscion regalis)
Authors: Litvin Steven Y , Weinstein Michael P
Published: January 2005

Canonical discriminant analysis of the natural carbon, nitrogen, and sulfur stable isotopes in tissues of young weakfish (Cynoscion regalis) captured in Delaware Bay was used to infer movements of juveniles and to estimate the utilization of estuarine organic matter in this marine transient species. Two gradients emerged in the data. The first was associated with contributions from tidal salt marsh macrophytes, Spartina alterniflora in the polyhaline lower Bay and Phragmites australis in the brackish upper Bay. The second was associated with the expected change in phytoplankton carbon-isotope values along the salinity gradient in addition to the availability of macrophyte-derived organic matter within the Bay. The separation of the gradients reflected differences in the relative contribution of phytoplankton to weakfish secondary production in open waters versus marsh habitats. As they grew, discrepancies between the anticipated isotopic signatures of juvenile weakfish collected in a specific habitat and their actual signatures were interpreted as down-bay movements based on known life-history patterns. The size-specific differences in the isotopic signatures of weakfish suggested that stable-isotope data can be used to gauge the relative magnitude of marsh-derived organic matter exported from Delaware Bay via movements of juveniles out of the estuary.
Nonparametric estimates of age misclassification from paired readings
Authors: Clark William G
Published: January 2005

With a large enough sample, age misclassification probabilities can be estimated nonparametrically by fitting the observed distribution of differences between paired readings. Application of this procedure to Pacific halibut data reveals that the unsigned deviations of single readings from the mode follow a geometric distribution, leading to a simple specification of misclassification probabilities. The potential for bias in this and other published procedures is discussed.
Effects of clay turbidity and light on the predatorprey interaction between smelts and chaoborids
Authors: Horppila Jukka , Liljendahl-Nurminen Anne , Malinen Tommi
Published: January 2005

The effects of clay turbidity and light on the predatorprey interaction between planktivorous smelts (Osmerus eperlanus) and phantom midge (Chaoborus flavicans) larvae were studied by means of laboratory experiments. Irrespective of light intensity, fish-mediated mortality of chaoborid larvae was highest at intermediate turbidity (20 nephelometric turbidity units (NTU)). Increases in light intensity enhanced the feeding rate of smelts at very low light intensities. A regression model describing the dependence of smelt-mediated mortality of chaoborids on light intensity and turbidity was fitted to the data. The model suggested that turbidity exceeding 30 NTU combined with light intensity below 0.1 µE·m2·s1provides an efficient daytime refuge for chaoborids even in the presence of planktivorous smelts. In the field studies, the depth distribution of chaoborids followed the predictions of the model. The depth at which chaoborid density was highest depended on the existence and location of the thermocline, the densest swarms occurring beneath the turbidity maximum in the metalimnion. The smelts occupied water layers above the chaoborids, suggesting that the chaoborids used the steep turbidity gradient in the thermocline as a shelter against predation.
A genetic perspective on management and recovery of federally endangered trout (Oncorhynchus gilae) in the American Southwest
Authors: Wares John P , Alò Dominique , Turner Thomas F
Published: January 2005

The native trout of New Mexico and Arizona have been managed for conservation for almost 80 years and are currently listed under the US Endangered Species Act. Management of these populations has improved the outlook for these species. However, because of a history of non-native salmonids being stocked in the region, genetic analysis of the remaining populations is necessary to ensure that each population is as representative as possible of ancestral populations of Gila (Oncorhynchus gilae) and Apache (Oncorhynchus gilae apache) trout. Here we provide a multi locus genotypic assessment of 19 populations of native southwestern trout that strongly indicates that management has maintained the genetic integrity of these species, while restoring each species to a number of historically occupied streams.
Long-term survival of adult Arctic grayling (Thymallus arcticus) in the Kuparuk River, Alaska
Authors: Buzby Karen M , Deegan Linda A
Published: January 2005

In many long-lived species such as Arctic grayling (Thymallus arcticus), population growth rate is most sensitive to changes in adult survival probabilities. Understanding the factors that regulate adult survival in this species should provide insight into the population dynamics of this and other long-lived Arctic species. Using the program MARK, we analyzed 17 years of markrecapture data to estimate survival rates for Arctic grayling in the Kuparuk River, Alaska, from 1985 to 2000. Mean annual survival rates overall ranged from 0.39 to 1.0 and averaged 0.71 ± 0.05 for resident and 0.75 ± 0.05 for nonresident fish. Spending the summer in the more productive fertilized zone of the experimental reach had no influence on survival despite higher productivity on all trophic levels and consistently higher growth rates in Arctic grayling. None of the environmental (stream temperature, discharge, winter severity, and incidence of drought) or population parameters (growth, condition factor, and mean fish size) that we examined explained significant amounts of variance in survival rates. The lack of responsiveness of survival to annual environmental conditions was unexpected and suggests that multiyear factors or life history tactics that maintain survival at the expense of growth and fecundity likely determine survival.
Copper inhibition of phytoplankton in Saginaw Bay, Lake Huron
Authors: Lehman John T , Bazzi Ali , Nosher Todd , Nriagu Jerome O
Published: January 2005

Field surveys and bioassays during 1999 and 2000 demonstrated trace metal effects on the phytoplankton of inner and outer regions of Saginaw Bay, Lake Huron. Addition of as little as 1 µg·L1 copper suppressed algal biomass, measured as particulate chlorophyll a, compared with control treatments, additions of ethylenediaminetetraacetic acid, or additions of carrier water alone. Suppression effects of copper, added alone or in combination with cadmium, lead, and thallium, were evident in inner and outer regions of Saginaw Bay during both spring and summer when phytoplankton communities were composed alternatively of diatoms and cyanobacteria. Experimental treatments were conducted in parallel with measurements of metal concentrations and metal complexation capacities of lake water collected by ultraclean trace metal techniques. Despite apparent overchelation of dissolved copper by organic ligands in Saginaw Bay, additions of a few tens of nanomoles of copper per litre strongly reduces algal biomass compared with control treatments. These results suggest that metal concentrations in some Great Lakes waters in equilibrium with natural chelators may be above the essential requirements and potentially at levels of incipient toxicity to the native phytoplankton communities.
Functional significance of the LAR receptor protein tyrosine phosphatase family in development and diseases
Authors: Chagnon Mélanie J , Uetani Noriko , Tremblay Michel L
Published: January 2005

The protein tyrosine phosphatases (PTPs) have emerged as critical players in diverse cellular functions. The focus of this review is the leukocyte common antigen-related (LAR) subfamily of receptor PTPs (RPTPs). This subfamily is composed of three vertebrate homologs, LAR, RPTP-sigma, and RPTP-delta, as well as few invertebrates orthologs such as Dlar. LAR-RPTPs have a predominant function in nervous system development that is conserved throughout evolution. Proteolytic cleavage of LAR-RPTP proproteins results in the noncovalent association of an extracellular domain resembling cell adhesion molecules and intracellular tandem PTPs domains, which is likely regulated via dimerization. Their receptor-like structures allow them to sense the extracellular environment and transduce signals intracellularly via their cytosolic PTP domains. Although many interacting partners of the LAR-RPTPs have been identified and suggest a role for the LAR-RPTPs in actin remodeling, very little is known about the mechanisms of action of RPTPs. LAR-RPTPs recently raised a lot of interest when they were shown to regulate neurite growth and nerve regeneration in transgenic animal models. In addition, LAR-RPTPs have also been implicated in metabolic regulation and cancer. This RPTP subfamily is likely to become important as drug targets in these various human pathologies, but further understanding of their complex signal transduction cascades will be required.Key words: protein tyrosine phosphatase, LAR, signal transduction, nervous system development.
Inverse agonism: more than reverting constitutively active receptor signaling
Authors: Dupré Denis J , Rola-Pleszczynski Marek , Staňková Jana
Published: January 2005

Seven-transmembrane receptors constitute one of the major families of proteins encoded by the genome. This type of receptor is one of the most important targets of the pharmaceutical industry, and many of the drugs with significant therapeutic action have been shown to be inverse agonists. Concepts regarding the mechanisms by which ligands activate and inactivate receptors are thought to be far more complex that a simple on–off switch. For both drug design and pharmacology principles, it is important to understand the mechanisms by which these drugs achieve their effects. Recent studies have demonstrated intriguing actions of inverse agonists. They have been shown not only to block constitutive responses of receptors but also to activate and regulate seven-transmembrane receptor signaling and trafficking. The activation of pathways by inverse agonists was shown to occur mainly via G-protein-independent mechanisms. These findings emphasize the importance of inverse agonism as a principle of receptor regulation. In this paper, we will review the evidence supporting inverse agonist promoted signaling and trafficking.Key words: G-protein-coupled receptor, seven-transmembrane receptor, inverse agonist, platelet-activating factor receptor, β2-adrenergic receptor.