bluuebunny/crossref_metadata_2025 huggingface dataset:
In VitroActivity of Daptomycin against Vancomycin-Resistant Enterococci ofVarious Van Types and Comparison of Susceptibility TestingMethods
Authors: Jorgensen James H. , Crawford Sharon A. , Kelly Cynthia C. , Patterson Jan E.
Published: November 2003

The
increasing prevalence of vancomycin-resistant enterococcal (VRE)
infections and the limited number of antimicrobial agents for their
treatment emphasize a need for new, more effective agents. In this
study, the in vitro activity of daptomycin was determined against a
collection of 156 VRE from seven different institutions. Van types were
characterized by PCR, and pulsed-field gel electrophoresis was
performed to exclude isolates with >85% relatedness by
dendrogram. Included were 126
Enterococcus faecium
(109
vanA
, 17
vanB
) isolates, 5
Enterococcus
faecalis
(3
vanA
, 2
vanB
) isolates, 2
Enterococcus avium
(
vanA
) isolates, 1
Enterococcus durans
(
vanA
) isolate, 10
Enterococcus gallinarum
(
vanC1
) isolates, and 12
Enterococcus casseliflavus
(
vanC2
) isolates. MICs of
daptomycin and five additional agents were determined by the NCCLS
broth microdilution method with Mueller-Hinton (MH) broth containing
supplemental calcium. MICs were also determined using two
investigational E-test strip formulations, and disk diffusion testing
was performed by the standard NCCLS method. The MIC of daptomycin at
which 50% of the isolates tested were inhibited for this isolate
collection was 4 μg/ml, and the MIC at which 90% of the
isolates tested were inhibited was 8 μg/ml. Two isolates of
vanA E. faecium
were resistant to linezolid, and one isolate
was resistant to quinupristin-dalfopristin. MICs of daptomycin
determined by the E test with and without added calcium varied by 8- to
16-fold, and disk diffusion zones varied by 3 to 6 mm according to the
calcium content of the commercial MH agar lots used in the study. This
study has shown daptomycin to have good activity against a diverse
collection of contemporary VRE isolates. However, improved
standardization of the calcium content of MH agar will be important for
reliable testing of daptomycin by clinical laboratories using either
the E test or disk diffusion
methods.
Nitazoxanide in Treatment of
Helicobacterpylori
: a Clinical and In VitroStudy
Authors: Guttner Yvonne , Windsor Helen M. , Viiala Charlie H. , Dusci Leon , Marshall Barry J.
Published: November 2003

Nitazoxanide
(NTZ) is an antibiotic with microbiological characteristics similar to
those of metronidazole but without an apparent problem of resistance.
The aim of this study was the prospective evaluation of NTZ given as a
single agent in the treatment of
Helicobacter pylori
infection. Twenty culture-positive patients with dyspepsia who had
previously failed at least one course of
H. pylori
eradication
therapy were enrolled. Subjects received 1 g of NTZ twice
daily for 10 days. The safety and tolerability of the drug were
assessed by physical examination, monitoring of adverse events, and
clinical laboratory evaluation. Urea breath tests (UBTs) were performed
6 weeks posttreatment.
H. pylori
was isolated from
UBT-positive patients by the string test or endoscopy with biopsy, and
the MICs for these isolates were compared to those for isolates
obtained pretherapy. The levels of tizoxanide, the active deacylated
derivative of NTZ, were measured in blood, saliva, and tissue from two
patients during treatment. The UBT results were positive for all 20
patients after completion of NTZ therapy. The MIC results demonstrated
that the NTZ susceptibilities of none of the strains isolated from the
patients posttherapy had changed significantly. No major adverse
reactions were observed, but frequent minor side effects were observed.
In conclusion, NTZ did not eradicate
H. pylori
when it was
given as a single
agent.
ethA
,
inhA
, and
katG
Loci of Ethionamide-Resistant Clinical
Mycobacterium tuberculosis
Isolates
Authors: Morlock Glenn P. , Metchock Beverly , Sikes David , Crawford Jack T. , Cooksey Robert C.
Published: November 2003

Ethionamide
(ETH) is a structural analog of the antituberculosis drug isoniazid
(INH). Both of these drugs target InhA, an enzyme involved in mycolic
acid biosynthesis. INH requires catalase-peroxidase (KatG) activation,
and mutations in
katG
are a major INH resistance mechanism.
Recently an enzyme (EthA) capable of activating ETH has been
identified. We sequenced the entire
ethA
structural gene of 41
ETH-resistant
Mycobacterium tuberculosis
isolates. We also
sequenced two regions of
inhA
and all or part of
katG.
The MICs of ETH and INH were determined in order to
associate the mutations identified with a resistance phenotype. Fifteen
isolates were found to possess
ethA
mutations, for all of
which the ETH MICs were ≥50 μg/ml. The
ethA
mutations were all different, previously unreported, and distributed
throughout the gene. In eight of the isolates, a missense mutation in
the
inhA
structural gene occurred. The ETH MICs for seven of
the InhA mutants were ≥100 μg/ml, and these isolates
were also resistant to ≥8 μg of INH per ml. Only a
single point mutation in the
inhA
promoter was identified in
14 isolates. A
katG
mutation occurred in 15 isolates, for
which the INH MICs for all but 1 were ≥32 μg/ml. As
expected, we found no association between
katG
mutation and
the level of ETH resistance. Mutations within the
ethA
and
inhA
structural genes were associated with relatively high
levels of ETH resistance. Approximately 76% of isolates
resistant to ≥50 μg of ETH per ml had such
mutations.
Antipneumococcal Activity of DK-507k, a New Quinolone,Compared with the Activities of 10 OtherAgents
Authors: Browne Frederick A. , Bozdogan Bülent , Clark Catherine , Kelly Linda M. , Ednie Lois , Kosowska Klaudia , Dewasse Bonifacio , Jacobs Michael R. , Appelbaum Peter C.
Published: November 2003

Agar
dilution MIC determination was used to compare the activity of DK-507k
with those of ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin,
sitafloxacin, amoxicillin, cefuroxime, erythromycin, azithromycin, and
clarithromycin against 113 penicillin-susceptible, 81
penicillin-intermediate, and 67 penicillin-resistant pneumococci (all
quinolone susceptible). DK-507k and sitafloxacin had the lowest MICs of
all quinolones against quinolone-susceptible strains (MIC at which
50% of isolates were inhibited [MIC
50
] and
MIC
90
of both, 0.06 and 0.125 μg/ml, respectively),
followed by moxifloxacin, gatifloxacin, levofloxacin, and
ciprofloxacin. MICs of β-lactams and macrolides rose with those
of penicillin G. Against 26 quinolone-resistant pneumococci with known
resistance mechanisms, DK-507k and sitafloxacin were also the most
active quinolones (MICs, 0.125 to 1.0 μg/ml), followed by
moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. Mutations
in quinolone resistance-determining regions of quinolone-resistant
strains were in the usual regions of the
parC
and
gyrA
genes. Time-kill testing showed that both DK-507k and
sitafloxacin were bactericidal against all 12 quinolone-susceptible and
-resistant strains tested at twice the MIC at 24 h. Serial
broth passages in subinhibitory concentrations of 10 strains for a
minimum of 14 days showed that development of resistant mutants
(fourfold or greater increase in the original MIC) occurred most
rapidly for ciprofloxacin, followed by moxifloxacin, DK-507k,
gatifloxacin, sitafloxacin, and levofloxacin. All parent strains
demonstrated a fourfold or greater increase in initial MIC in<50 days. MICs of DK-507k against resistant mutants were
lowest, followed by those of sitafloxacin, moxifloxacin, gatifloxacin,
ciprofloxacin, and levofloxacin. Four strains were subcultured in
subinhibitory concentrations of each drug for 50 days: MICs of DK-507k
against resistant mutants were lowest, followed by those of
sitafloxacin, moxifloxacin, gatifloxacin, levofloxacin, and
ciprofloxacin. Exposure to DK-507k and sitafloxacin resulted in
mutations, mostly in
gyrA
.
Antimicrobial Resistance in
Campylobacterjejuni
and
Campylobacter coli
Strains Isolated in 1991and 2001-2002 from Poultry and Humans in Berlin,Germany
Authors: Luber Petra , Wagner Jutta , Hahn Helmut , Bartelt Edda
Published: November 2003

The
susceptibilities of 430
Campylobacter jejuni
strains and 79
C. coli
strains to six antimicrobial agents were tested and
analyzed. The two sets of strains originated from retail market chicken
and turkey samples and from humans, respectively, in Berlin, Germany.
Two groups of isolates, one dating from 1991 and the other dating from
2001-2002, were tested. Of the
Campylobacter
sp. isolates
recovered from humans in 2001-2002, 45.1% were resistant to
ciprofloxacin, 37.8% were resistant to tetracycline,
12.8% were resistant to ampicillin, and 50.0% were
resistant to trimethoprim-sulfamethoxazole. All isolates were
susceptible to gentamicin, while the overall rate of resistance to
erythromycin was 6.1%. During the 10 years between the two
sampling times, the rates of resistance to ciprofloxacin (
P
< 0.001), ampicillin (
P
= 0.035), and
tetracycline (
P
= 0.01) increased significantly among
strains isolated from humans. Furthermore, among human
C. coli
strains the rate of resistance to erythromycin rose from 7.1% in
1991 to 29.4% in 2001-2002. In comparison,
Campylobacter
sp. isolates from poultry already had high rates
of resistance in 1991. Different rates of resistance to tetracycline
among isolates from chickens and turkeys suggested the development of
resistance during antimicrobial treatment in food animals. Thus,
discrepancies in the antimicrobial resistance rates among
Campylobacter
isolates originating from poultry and humans
support the hypothesis that at least some of the resistant
Campylobacter
strains causing infection in humans come from
sources other than poultry
products.
GeneHunter, a Transposon Tool for Identificationand Isolation of Cryptic Antibiotic ResistanceGenes
Authors: Salipante Stephen J. , Barlow Miriam , Hall Barry G.
Published: November 2003

GeneHunter
is a transposon tool designed for the experimental activation and
identification of silent antibiotic resistance genes. The method
permits the identification of novel resistance genes that lack
previously identified homologues. Using
Salmonella enterica
serovar Typhimurium strain LT2 as a test organism for the in vivo
version of the GeneHunter method, we were able to activate, clone, and
identify two cryptic antibiotic resistance genes, the aminoglycoside
acetyltransferase
aac(6′)-Iaa
and the probable Mar-A
regulon activator
rma
. Because the method requires being able
to electroporate the host with an efficiency of at least
10
10
transformants per microgram, the in vivo method is not
applicable to most microorganisms. We therefore developed an in vitro
transposition method, showed that it can also recover the cryptic
rma
gene from S. enterica serovar Typhimurium strain LT2, and
showed that it is generally applicable to a variety of microorganisms
by using it to recover a cryptic metallo-β-lactamase gene from
the gram-positive organism
Bacillus cereus
. It is anticipated
that the GeneHunter method will be used to identify potential
resistance genes during the development and testing of novel
antibiotics, new variants of existing antibiotics, and drug inhibitor
combinations.
Molecular Mechanism of Terbinafine Resistance in
Saccharomycescerevisiae
Authors: Leber Regina , Fuchsbichler Sandra , Klobučníková Vlasta , Schweighofer Natascha , Pitters Eva , Wohlfarter Kathrin , Lederer Mojca , Landl Karina , Ruckenstuhl Christoph , Hapala Ivan , Turnowsky Friederike
Published: November 2003

Ten
mutants of the yeast
Saccharomyces cerevisiae
resistant to the
antimycotic terbinafine were isolated after chemical or UV mutagenesis.
Molecular analysis of these mutants revealed single base pair exchanges
in the
ERG1
gene coding for squalene epoxidase, the target of
terbinafine. The mutants did not show cross-resistance to any of the
substrates of various pleiotropic drug resistance efflux pumps tested.
The
ERG1
mRNA levels in the mutants did not differ from those
in the wild-type parent strains. Terbinafine resistance was transmitted
with the mutated alleles in gene replacement experiments, proving that
single amino acid substitutions in the Erg1 protein were sufficient to
confer the resistance phenotype. The amino acid changes caused by the
point mutations were clustered in two regions of the Erg1 protein.
Seven mutants carried the amino acid substitutions F
402
L
(one mutant), F
420
L (one mutant), and P
430
S (five
mutants) in the C-terminal part of the protein; and three mutants
carried an L
251
F exchange in the central part of the
protein. Interestingly, all exchanges identified involved amino acids
which are conserved in the squalene epoxidases of yeasts and mammals.
Two mutations that were generated by PCR mutagenesis of the
ERG1
gene and that conferred terbinafine resistance mapped in
the same regions of the Erg1 protein, with one resulting in an
L
251
F exchange and the other resulting in an
F
433
S exchange. The results strongly indicate that these
regions are responsible for the interaction of yeast squalene epoxidase
with
terbinafine.
Novispirin G10-Induced Lung Toxicity in aKlebsiella pneumoniaeInfectionModel
Authors: Bartlett Karen H. , McCray Paul B. , Thorne Peter S.
Published: November 2003

Mammalian cathelicidins are a class of innate antimicrobial peptides isolated from leukocytes and epithelial cells that aid host defense against bacterial infections. Synthetic analogs of cathelicidins offer the promise of potent broad-spectrum antimicrobial efficacy. We developed a combined lung infection and ex vivo whole-blood assay model to characterize the toxicity and efficacy of synthetic cathelicidin-derived peptides. Male C57BL/6 mice were administered saline orKlebsiella pneumoniaeby intratracheal instillation. Five hours later, theKlebsiella-infected mice were instilled with saline, tobramycin (1 mg/kg of body weight or 10 mg/kg), novispirin G10 (0.4 mg/kg), or a combination of tobramycin (1 mg/kg) and G10 (0.4 mg/kg). At 24 h, bronchoalveolar lavage fluid (BAL) was collected for analysis of culturable bacteria and for markers of inflammation and lung toxicity. Blood samples were analyzed for circulating cytokines. Recovery ofKlebsiellafrom the lung, recruitment of neutrophils, and production of interleukin-6 (IL-6) in BAL samples were highly correlated (r= 0.68 and 0.84, respectively;P< 0.01). Animals treated with G10 or G10 plus tobramycin had increased hemoglobin (P< 0.001) and protein (P< 0.001) levels compared to those forKlebsiella-infected or tobramycin-alone-treated animals. The levels of circulating IL-6 in mice infected withKlebsiellawere 1000- to 10,000-fold higher than in the noninfected controls. The highest levels of IL-6 were measured in mice given G10 alone or in combination with tobramycin. These studies demonstrated that G10 was relatively nontoxic in saline-treated mice but was highly toxic in mice infected withKlebsiella. This finding establishes the importance of investigating candidate antimicrobial agents in an in vivo infection model.
Phase II, Randomized, Double-Blind, Placebo-Controlled Studies of Ruprintrivir Nasal Spray 2-Percent Suspension for Prevention and Treatment of Experimentally Induced Rhinovirus Colds in Healthy Volunteers
Authors: Hayden Frederick G. , Turner Ronald B. , Gwaltney Jack M. , Chi-Burris Kathy , Gersten Merril , Hsyu Poe , Patick Amy K. , Smith George J. , Zalman Leora S.
Published: November 2003

Human rhinovirus (HRV) infections are usually self-limited but may be associated with serious consequences, particularly in those with asthma and chronic respiratory disease. Effective antiviral agents are needed for preventing and treating HRV illnesses. Ruprintrivir (Agouron Pharmaceuticals, Inc., San Diego, Calif.) selectively inhibits HRV 3C protease and shows potent, broad-spectrum anti-HRV activity in vitro. We conducted three double-blind, placebo-controlled clinical trials in 202 healthy volunteers to assess the activity of ruprintrivir in experimental HRV infection. Subjects were randomized to receive intranasal ruprintrivir (8 mg) or placebo sprays as prophylaxis (two or five times daily [2×/day or 5×/day] for 5 days) starting 6 h before infection or as treatment (5×/day for 4 days) starting 24 h after infection. Ruprintrivir prophylaxis reduced the proportion of subjects with positive viral cultures (for 5×/day dosing groups, 44% for ruprintrivir treatment group versus 70% for placebo treatment group [P= 0.03]; for 2×/day dosing groups, 60% for ruprintrivir group versus 92% for placebo group [P= 0.004]) and viral titers but did not decrease the frequency of colds. Ruprintrivir treatment reduced the mean total daily symptom score (2.2 for ruprintrivir treatment group and 3.3 for the placebo treatment group [P= 0.014]) by 33%. Secondary endpoints, including viral titers, individual symptom scores, and nasal discharge weights, were also reduced by ruprintrivir treatment. Overall, ruprintrivir was well tolerated; blood-tinged mucus and nasal passage irritation were the most common adverse effects reported. Pharmacokinetic analysis of plasma and nasal ruprintrivir concentrations revealed intranasal drug residence with minimal systemic absorption. Results from these studies in experimental rhinoviral infection support continued investigation of intranasal ruprintrivir in the setting of natural HRV infection.
Evolutionary Models of the Emergence ofMethicillin-Resistant
Staphylococcusaureus
Authors: Robinson D. Ashley , Enright Mark C.
Published: November 2003

Five
major lineages of methicillin-resistant
Staphylococcus aureus
(MRSA) have evolved since the introduction of methicillin for the
treatment of infections caused by penicillin-resistant
S.
aureus
in 1959. The clones of these lineages are responsible for
the vast majority of hospital-acquired MRSA disease globally. We have
constructed high-resolution evolutionary models for each lineage using
a parsimony approach with 15 partial gene sequences from 147
geographically diverse isolates. On the basis of these models, we infer
that MRSA has emerged at least 20 times upon acquisition of the
methicillin resistance determinant, which is carried on a mobile
genetic element called the staphylococcal cassette chromosome
mec
(SCC
mec
). The acquisition of SCC
mec
by
sensitive clones was four times more common than the replacement of one
SCC
mec
with another. Notably, SCC
mec
type IV was
found in twice as many clones as any other SCC
mec
type, and it
is this SCC
mec
type which is commonly found in clones from
patients with community-acquired MRSA disease. Our findings suggest
that most clones of MRSA arise by the acquisition of SCC
mec
type IV by methicillin-sensitive
isolates.
Pharmacodynamics of the New Des-F(6)-QuinoloneGarenoxacin in a Murine Thigh InfectionModel
Authors: Andes D. , Craig W. A.
Published: November 2003

Garenoxacin
is a new des-F(6)-quinolone with broad-spectrum activity against both
gram-positive cocci and gram-negative bacilli. We used the neutropenic
murine thigh infection model to characterize the time course of
antimicrobial activity of garenoxacin and determine which
pharmacokinetic-pharmacodynamic (PK-PD) parameter best correlated with
efficacy. Serum drug levels following three fourfold-escalating
single-dose levels of garenoxacin were measured by microbiologic assay.
In vivo postantibiotic effects (PAEs) were determined after doses of 16
and 64 mg/kg of body weight. Mice had 10
6.5
to
10
6.7
CFU of
Streptococcus pneumoniae
strain ATCC
10813 or
Staphylococcus aureus
strain ATCC 33591 per thigh
when they were treated for 24 h with garenoxacin at a dose of
4 to 128 mg/kg/day fractionated for 3-, 6-, 12-, and 24-hour dosing
regimens. Nonlinear regression analysis was used to determine which
PK-PD parameter best correlated with the measurement of CFU/thigh at
24 h. Pharmacokinetic studies yielded peak/dose values of 0.2
to 0.3, area under the concentration-time curve (AUC)/dose values of
0.1 to 0.5, and half-lives of 0.7 to 1.6 h. Garenoxacin
produced in vivo PAEs of 1.4 to 8.2 h with
S.
pneumoniae
ATCC 10813, 7.6 to >12.4 h with
S.
aureus
ATCC 25923, and 0 to 1.5 h with
Klebsiella
pneumoniae
ATCC 43816. The 24-h AUC/MIC ratio was the PK-PD
parameter that best correlated with efficacy (
R
2
=
71 to 90% for the two organisms compared with 43 to
56% for the peak/MIC ratio and 47 to 75% for percent time
above the MIC [%
T
>MIC]).In subsequent studies we used the neutropenic murine thigh infection
model to determine if the magnitude of the AUC/MIC ratio needed for
efficacy of garenoxacin varied among pathogens (including resistant
strains). Mice had 10
5.9
to 10
7.2
CFU of 6
strains of
S. aureus
(2 methicillin resistant), 11 strains of
S. pneumoniae
(5 penicillin susceptible, 1 penicillin
intermediate, and 5 penicillin resistant, and of the resistant strains,
3 were also ciprofloxacin resistant), and 4 gram-negative
strains per thigh when treated for 24 h with 1 to 64 mg of
garenoxacin per kg every 12 h. A sigmoid dose-response model
was used to estimate the doses (mg/kg/24 h) required to achieve a net
bacteriostatic effect over 24 h. MICs ranged from 0.008 to 4μ
g/ml. The free drug 24-h AUC/MIC ratios for each static dose
(2.8 to 128 mg/kg/day) varied from 8.2 to 145. The mean 24-h AUC/MIC
ratios ± standard deviations for
S. pneumoniae
,
S.
aureus
, and gram-negative strains were 33 ± 18, 81±
37, and 33 ± 30, respectively. Methicillin,
penicillin, or ciprofloxacin resistance did not alter the magnitude of
the AUC/MIC ratio required for
efficacy.
PlasmidContent of a Vancomycin-Resistant
Enterococcus faecalis
Isolate from a Patient Also Colonized by
Staphylococcusaureus
with a VanAPhenotype
Authors: Flannagan Susan E. , Chow Joseph W. , Donabedian Susan M. , Brown William J. , Perri Mary B. , Zervos Marcus J. , Ozawa Yoshiyuki , Clewell Don B.
Published: November 2003

Vancomycin-resistant
Enterococcus faecalis
coisolated with vancomycin-resistant
(VanA)
Staphylococcus aureus
was found to contain two
plasmids, designated pAM830 (45 kb) and pAM831 (95 kb). pAM830, found
to be conjugative and closely related to the Inc18 family of
broad-host-range conjugative plasmids, encodes resistances to
vancomycin (via a Tn
1546
-like element) and erythromycin;
pAM831 encodes resistances to gentamicin, streptomycin, and
erythromycin.
BactericidalActivities of Daptomycin, Quinupristin-Dalfopristin, and Linezolidagainst Vancomycin-ResistantStaphylococcus aureusinan In Vitro Pharmacodynamic Model with SimulatedEndocardialVegetations
Authors: Cha Raymond , Brown William J. , Rybak Michael J.
Published: November 2003

In search of treatment alternatives against vancomycin-resistantS. aureus(VRSA), an in vitro pharmacodynamic model with simulated endocardial vegetations incorporating protein and a high inoculum was used to simulate daptomycin, linezolid, quinupristin-dalfopristin, and vancomycin against the Michigan VRSA strain. Daptomycin and quinupristin-dalfopristin exhibited the greatest bacterial reductions, and all tested agents except vancomycin exhibited bactericidal activity against the VRSA.
InVitro Activity of Tigecycline against
Staphylococcusepidermidis
Growing in an Adherent-Cell BiofilmModel
Authors: Labthavikul Pornpen , Petersen Peter J. , Bradford Patricia A.
Published: November 2003

The
activity of tigecycline against
Staphylococcus epidermidis
growing in an in vitro adherent-cell biofilm model was determined.
Tigecycline minimum bactericidal concentrations (MBCs) ranged from 1 to
8 μg/ml for
S. epidermidis
growing in a biofilm of
adherent cells, compared to MBCs of 0.12 to >32 μg/ml
for freely growing cells. The killing activity of tigecycline against
the adherent bacteria was at least fourfold better than that of
vancomycin and
daptomycin.
ComparativeIn Vitro Susceptibilities and Bactericidal Activities ofInvestigational Fluoroquinolone ABT-492 and Other Antimicrobial Agentsagainst Human Mycoplasmas andUreaplasmas
Authors: Waites Ken B. , Crabb Donna M. , Duffy Lynn B.
Published: November 2003

We
determined in vitro susceptibilities for ABT-492 and other
antimicrobials against
Mycoplasma pneumoniae
,
Mycoplasma
fermentans
,
Mycoplasma hominis
, and
Ureaplasma
species. ABT-492 MICs were ≤1 μg/ml, and the agent was
bactericidal against selected isolates of
M. pneumoniae
and
M. hominis.
ABT-492 has potential for treatment of infections
due to these
microorganisms.
Genotypesof
Pneumocystis jiroveci
Isolates Obtained in Harare,Zimbabwe, and London, UnitedKingdom
Authors: Miller Robert F. , Lindley Austin R. , Ambrose Helen E. , Malin Adam S. , Wakefield Ann E.
Published: November 2003

Isolates
of
Pneumocystis jiroveci
from sulfa-exposed and nonexposed
patients from London, United Kingdom, and Harare, Zimbabwe, were
genotyped. At the dihydropteroate synthase (DHPS) locus, there was
evidence of selection pressure from sulfa drug exposure, and reversal
of DHPS genotype ratios occurred when selection pressure was absent or
was
removed.
Prevalence of Extended-Spectrum β-Lactamase-Producing
Enterobacter cloacae
in the Asia-Pacific Region: Results from the SENTRY Antimicrobial Surveillance Program, 1998 to 2001
Authors: Bell J. M. , Turnidge J. D. , Jones R. N. ,   the SENTRY Asia-Pacific Participants
Published: November 2003

Enterobacter
cloacae
strains from hospitalized patients with a range of
infections were collected by 17 laboratories in the Asia-Pacific region
and South Africa. Isolates for which ceftriaxone MICs were above 1μ
g/ml and/or ceftazidime MICs were above 2 μg/ml, as
well as 46 strains for which ceftriaxone and/or ceftazidime MICs were
at or below these values, were screened for levels of extended-spectrumβ
-lactamase (ESBL) production through the use of broth
microdilution for the detection of clavulanate enhancement of the
activity of ceftriaxone, ceftazidime, and cefepime. Of the isolates
examined, ceftriaxone and/or ceftazidime had elevated MICs for
44%, of which 36% were ESBL positive. ESBL-positive
strains were commonly susceptible to piperacillin-tazobactam and more
frequently resistant to several other antimicrobials studied. A
cefepime MIC above 0.25 μg/ml had the highest sensitivity
(100%) and specificity (74%) for predicting the presence
of an
ESBL.
AN IMPROVED QUANTUM SCHEDULING ALGORITHM
Authors: GROVER LOV K.
Published: November 2003

The scheduling problem consists of finding a common 1 in two remotely located N bit strings. Denote the number of 1s in the string with the fewer 1s by ∊N. Classically, it needs Ω(∊N log 2 N) bits of communication to find the common 1. The best known quantum algorithms require about [Formula: see text] qubits of communication. This paper gives a quantum algorithm to find the common 1 with only [Formula: see text] qubits of communication.
SEPARABILITY OF PURE N-QUBIT STATES: TWO CHARACTERIZATIONS
Authors: JORRAND PHILIPPE , MHALLA MEHDI
Published: November 2003

Given a pure state |ψN>∈ℋN of a quantum system composed of n qubits, where ℋN is the Hilbert space of dimension N=2n, this paper answers two questions: what conditions should the amplitudes in |ψN> satisfy for this state to be separable (i) into a tensor product of n qubit states |ψ2>0⊗ |ψ2>1 ⊗⋯⊗ |ψ2>n-1, and (ii), into a tensor product of two subsystems states |ψP> ⊗ |ψQ> with P=2p and Q=2q such that p+q=n? For both questions, necessary and sufficient conditions are proved, thus characterizing at the same time families of separable and entangled states of n qubit systems. A number of more refined questions about separability in n qubit systems can be studied on the basis of these results.
ANALYSIS OF QUANTUM FUNCTIONS
Authors: YAMAKAMI TOMOYUKI
Published: November 2003

This paper initiates a systematic study of quantum functions, which are (partial) functions defined in terms of quantum mechanical computations. Of all quantum functions, we focus on resource-bounded quantum functions whose inputs are classical bit strings. We prove complexity-theoretical properties and unique characteristics of these quantum functions by recent techniques developed for the analysis of quantum computations. We also discuss relativized quantum functions that make adaptive and nonadaptive oracle queries.
QUANTUM COMPUTATION WITH RESTRICTED AMPLITUDES
Authors: NISHIMURA HARUMICHI
Published: November 2003

In this paper, we explore the power of quantum computers with restricted transition amplitudes. In 1997 Adleman, DeMarrais, and Huang showed that quantum Turing machines (QTMs) with the amplitudes from [Formula: see text] are computationally equivalent to ones with the polynomial-time computable amplitudes as machines implementing bounded-error polynomial-time algorithms. We show that QTMs with the amplitudes from [Formula: see text] is polynomial-time equivalent to deterministic Turing machines as machines implementing exact algorithms, i.e., algorithms that output correct answers with certainty. By extending this result, it is shown that exact quantum computers with rational biased coins are equivalent to classical computers. Moreover, we discuss the computational power of exact quantum computers with multiple types of coins. We also show that, from the viewpoint of zero-error polynomial-time algorithms, [Formula: see text] is not more powerful than [Formula: see text] as the set of amplitudes taken by QTMs; however, it is sufficient to solve the factoring problem.
A ROBUST DNA COMPUTATION MODEL THAT CAPTURES PSPACE
Authors: DANTSIN EVGENY , WOLPERT ALEXANDER
Published: November 2003

One of the most serious problems in DNA computing is that basic DNA operations are faulty. Many DNA computation models use operations based on annealing and magnetic-beads separation which sometimes produce undesirable results. Some models use reliable operations only but their computational power is too weak. The purpose of this paper is to find a good trade-off between the robustness of DNA operations and their computational power. We present a robust DNA computation model that can solve computationally hard problems. We prove that (i) this model can solve PSPACE-complete problems, and (ii) any computational problem that can be solved with this model is in PSPACE.
NOVEL STABILITY CRITERIA FOR DELAYED CELLULAR NEURAL NETWORKS
Authors: CAO JINDE , WANG JUN , LIAO XIAOFENG
Published: November 2003

In this paper, a new sufficient condition is given for the global asymptotic stability and global exponential output stability of a unique equilibrium points of delayed cellular neural networks (DCNNs) by using Lyapunov method. This condition imposes constraints on the feedback matrices and delayed feedback matrices of DCNNs and is independent of the delay. The obtained results extend and improve upon those in the earlier literature, and this condition is also less restrictive than those given in the earlier references. Two examples compared with the previous results in the literatures are presented and a simulation result is also given.
Effects of Unkei-to on FSH, LH and Estradiol in Anovulatory Young Women with Hyper- or Hypo-Functioning Conditions
Authors: Ushiroyama Takahisa , Hosotani Toshimitsu , Yamashita Yoshiki , Yamashita Hidetoshi , Ueki Minoru
Published: November 2003

Eight weeks treatment with Unkei-to induced a significant increase in plasma follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol levels in hyper- (robust) and hypo- (asthenia) functioning patients with first- and second-grade amenorrhea. We observed no significant differences in the rate of change of these hormones between hyper- and hypo-functioning patients. Ovulation occurred in 61.3% and 66.7% of patients with first-grade amenorrhea, and in 27.3% and 22.4% of patients with second-grade amenorrhea, respectively. No significant difference was observed in the ovulation rate after an 8-week treatment with Unkei-to between hyper- and hypo-functioning patients.

These results indicate that Unkei-to is effective in improving gonadotropin and estradiol secretion in the treatment of either hyper- or hypo-functioning anovulatory women.
Effects of Traditional Chinese Medicines on Murine Bone Metabolism in a Microgravity Environment
Authors: Song Qing-Hua , Kobayashi Takao , Hosoi Takayuki , Cyong Jong-Chol
Published: November 2003

We investigated the effects of three traditional Chinese medicine prescriptions on changes of bone metabolism in mice, using a gravity device to produce a microgravity environment. We found that Hochu-ekki-to (TJ-41) and Hachimi-jio-gan (TJ-7) suppress the increase in the ratio of serum Ca/P and the increase of calcium in urine. Moreover, TJ-41 and Shin-bu-to (TJ-30) reversed the increase of alkaline phosphatase activity (ALP), and TJ-41 also reversed the decrease of estradiol in the serum. The mechanism may be that the traditional Chinese medicines increased estradiol, causing the decrease of ALP, which induced the changes of Ca and P in serum, leading to a decreased excretion of Ca in urine. In this study, TJ-41 was effective in every parameter while TJ-7 and TJ-30 was effective on some parameters, showing that traditional Chinese medicines have specificities in the space environment. In conclusion, this study suggests that some traditional Chinese medicines may be beneficial for adaptation to a space environment.
Prevention of Experimentally-induced Gastric Ulcers in Rats by an Ethanolic Extract of "Parsley"Petroselinum crispum
Authors: Al-Howiriny Tawfeq , Al-Sohaibani Mohammed , El-Tahir Kamal , Rafatullah Syed
Published: November 2003

An ethanolic extract of Parsley, Petroselinum crispum (Mill.) Nym.ex A.W. Hill (Umbelliferae), was tested for its ability to inhibit gastric secretion and to protect gastric mucosa against the injuries caused by pyloric ligation, hypothermic restraint stress, indomethacin and cytodestructive agents (80% ethanol, 0.2 M NaOH and 25% NaCl) in rats. The extract in doses of 1 and 2 g/kg body weight had a significant antiulcerogenic activity on the models used. Besides, ethanol-induced depleted gastric wall mucus and non-protein sulfhydryl contents were replenished by pretreatment with Parsley extract. Acute toxicity tests showed a large margin of safety for the extract. The phytochemical screening of Parsley leaves revealed the presence of tannins, flavonoids, sterols and/or triterpenes.
Protective Effect of Shenqi-wan Against H2O2-induced Apoptosis in Hippocampal Neuronal Cells
Authors: Shin Hyun-Taeg , Chung Seok-Hee , Lee Jong-Soo , Kim Sung-Soo , Shin Hyun-Dae , Jang Mi-Hyeon , Shin Min-Chul , Bahn Geon-Ho , Paik Eun-Kyung , Park Jae-Hyung , Kim Chang-Ju
Published: November 2003

The present study investigated whether Shenqi-wan possesses a protective effect against hydrogen peroxide ( H 2 O 2)-induced apoptosis of the hippocampal cell line HiB5. Through morphological and biochemical analyses, it was demonstrated that HiB5 cells treated with H 2 O 2 exhibited several apoptotic features, while cells pre-treated with Shenqi-wan prior to H 2 O 2 exposure showed a decrease in the occurrence of apoptosis. In addition, a patch clamp study revealed that Shenqi-wan inhibited profoundly N-methyl-D-aspartic acid (NMDA) receptor-activated ion current in acutely dissociated hippocampal CA1 neurons. These results suggest that Shenqi-wan may exert its protective effect against H 2 O 2-induced apoptosis via inhibition of NMDA receptors in hippocampal neuronal cells.
SOLAR NEUTRINO RESULTS FROM SUPER-KAMIOKANDE
Authors: TAKEUCHI YASUO
Published: November 2003

The solar neutrino results from 1496days of measurement from Super-Kamiokande-I (SK-I) are reported. The accident at SK-I, rebuilding of SK-II detector, and some prospects for SK-II are also reported briefly.
RESULTS FROM THE PURE D2O PHASE OF THE SUDBURY NEUTRINO OBSERVATORY
Authors:   FOR THE SNO COLLABORTION., DUNCAN F. A.
Published: November 2003

The Sudbury Neutrino Observatory is a 1000 T D2O Cerenkov detector that is sensitive to 8 B and hep solar neutrinos. Both Charged Current and Neutral Current interaction rates on deuterons as well as the Elastic Scattering interaction rate on electrons can be measured simultaneously. Assuming an undistorted 8 B neutrino spectrum, the total flux measured with the NC reaction is [Formula: see text], which is consistent with solar models. The νe component of the 8 B solar flux is [Formula: see text] for a kinetic energy threshold of 5 MeV. The non-νe component is [Formula: see text], which is 5.3σ greater than zero, giving strong evidence for solar νe flavor transformation. The Day-Night Asymmetry for the Charged Current interaction is [Formula: see text]. If the total flux of active neutrinos is additionally constrained to have no asymmetry, the νe asymmetry is found to be [Formula: see text]. Combined with other solar neutrino data, a global MSW oscillation analysis strongly favors the Large Mixing Angle (LMA) solution.
NEUTRINO MASSES, OSCILLATIONS, AND TESTS WITH FUTURE SUPERBEAMS AND A NEUTRINO FACTORY
Authors: LINDNER M.
Published: November 2003

Future long baseline neutrino oscillation (LBL) setups are discussed and the remarkable potential for very precise measurements of mass splittings, mixing angles, MSW effects, the sign of Δm2 and leptonic CP violation is shown. Furthermore we discuss the sensitivity improvements which can be obatined by combining the planned JHF-Superkamiokande and the proposed NuMI off-axis experiment.
ALTERNATIVES TO THE SEESAW: EXTRA Z'S AND CONSTRAINTS ON LARGE EXTRA DIMENSIONS
Authors: LANGACKER PAUL
Published: November 2003

Alternatives to the traditional grand unified theory seesaw for neutrino masses are briefly described. These include the possibility of large extra dimensions and various possibilities for models involving an extra U(1)′ gauge symmetry. The difficulty of observing Majorana phases in neutrinoless double beta decay is also briefly commented on.
VERY LONG BASELINE NEUTRINO OSCILLATION EXPERIMENTS FOR PRECISE MEASUREMENTS OF OSCILLATION PARAMETERS AND SEARCH FOR CP VIOLATION
Authors: DIWAN MILIND V.
Published: November 2003

We analyze the prospects of a feasible, very long baseline neutrino oscillation experiment consisting of a conventional horn produced low energy wide band beam and a detector of 500 kT fiducial mass with modest requirements on event recognition and resolution. Such an experiment is intended primarily to measure CP invariance parameters in the neutrino sector. We analyze the sensitivity of such an experiment. The conclusion is that it will allow determination of the CP parameter δCP, if the currently unknown mixing parameter sin 22θ13 ≥ 0.01, a value about 10 times lower than the present experimental upper limit. Such an experiment has great potential for precise measurements of all parameters in the neutrino mixing matrix including [Formula: see text], sin 22θ23, [Formula: see text], and the mass ordering of neutrinos through the observation of the matter effect in the νμ → νe appearance channel.
ULTRAHIGH ENERGY NEUTRINOS
Authors: DUTTA SHARADA IYER , RENO MARY HALL , SARCEVIC INA
Published: November 2003

The ultrahigh energy neutrino cross section is well understood in the standard model for neutrino energies up to 1012 GeV, Tests of neutrino oscillations (νμ ↔ ντ) from extragalactic sources of neutrinos are possible with large underground detectors. Measurements of horizontal air shower event rates at neutrino energies above 1010 GeV will be able to constrain nonstandard model contributions to the neutrino-nucleon cross section, e.g., from mini-black hole production.
TO BE OR NOT TO BE? — FIRST EVIDENCE FOR NEUTRINOLESS DOUBLE-BETA DECAY
Authors:   Spokesman of HEIDELBERG-MOSCOW and GENIUS Collaborations., KLAPDOR-KLEINGROTHAUS H. V.
Published: November 2003

Double beta decay is indispensable to solve the question of the neutrino mass matrix together with ν oscillation experiments. Recent analysis of the most sensitive experiment since nine years - the HEIDELBERG-MOSCOW experiment in Gran-Sasso - yields a first indication for the neutrinoless decay mode. This result is the first evidence for lepton number violation and proves the neutrino to be a Majorana particle. We give the present status of the analysis in this report. It excludes several of the neutrino mass scenarios allowed from present neutrino oscillation experiments - only degenerate scenarios and those with inverse mass hierarchy survive. This result allows neutrinos to still play an important role as dark matter in the Universe. To improve the accuracy of the present result, considerably enlarged experiments are required, such as GENIUS. A GENIUS Test Facility has been funded and will come into operation by early 2003.
A NATIONAL UNDERGROUND SCIENCE AND ENGINEERING LABORATORY
Authors: BOWLES THOMAS J.
Published: November 2003

Dramatic progress has been made in the last several years in our understanding of the properties of neutrinos with evidence for neutrino flavor transformation coming from measurements of atmospheric neutrinos by SuperKamiokande, of solar neutrinos by the Sudbury Neutrino Observatory (SNO), and of reactor neutrinos by KamLAND. These results are a step in the ongoing program of science that is carried out in underground laboratories. The potential for additional significant discoveries with new capabilities in underground laboratories exists and should be exploited. Discoveries are likely to be made not only in nuclear and particle physics, but also in astrophysics, geophysics, and geobiology. A concerted effort is now underway in the United States to create a National Underground Science and Engineering Laboratory (NUSEL) that would provide the facilities and infrastructure necessary to capitalize on the opportunities presented by underground science.
IMPRECISE PREVISIONS FOR RISK MEASUREMENT
Authors: PELESSONI RENATO , VICIG PAOLO
Published: November 2003

In this paper the theory of coherent imprecise previsions is applied to risk measurement. We introduce the notion of coherent risk measure defined on an arbitrary set of risks, showing that it can be considered a special case of coherent upper prevision. We also prove that our definition generalizes the notion of coherence for risk measures defined on a linear space of random numbers, given in literature. Consistency properties of Value-at-Risk (VaR), currently one of the most used risk measures, are investigated too, showing that it does not necessarily satisfy a weaker notion of consistency called 'avoiding sure loss'. We introduce sufficient conditions for VaR to avoid sure loss and to be coherent. Finally we discuss ways of modifying incoherent risk measures into coherent ones.
DISTRIBUTIVE IDEMPOTENT UNINORMS
Authors: RUIZ D. , TORRENS J.
Published: November 2003

A characterization of all idempotent uninorms satisfying the distributive property is given. The special cases of left-continuous and right-continuous idempotent uninorms are presented separately and it is also proved that all idempotent uninorms are autodistributive. Moreover, all distributive pairs of idempotent uninorms (pairs U1, U2 such that Ul is distributive over U2 and U2 is distributive over U1) are also characterized.
AN AGENT-BASED APPROACH TO IDENTIFICATION OF PREDICTION MODELS
Authors: MA TIEJU , NAKAMORI YOSHITERU
Published: November 2003

This paper presents an agent-based approach to identification of prediction models in two-dimensional data spaces. A number of agents are sent to the two-dimensional data space that people want to investigate. At the micro-level, every agent tries to build a local linear model by competing with others, and then at the macro-level all surviving agents build the global model by cooperating with each other. And a genetic algorithm is introduced for improving the global model built by the agents. Two examples that apply this approach are given. The advantages of this approach are it does not need people to give a certain formula in advance; and most of time, it can give more precise prediction models than those given by traditional methods.
CANONICAL FORM AND SEPARABILITY OF PPT STATES IN ${\mathcal C}^2\otimes
{\mathcal C}^M\otimes {\mathcal C}^N$ COMPOSITE QUANTUM SYSTEMS
Authors: WANG XIAO-HONG , FEI SHAO-MING , WANG ZHI-XI , WU KE
Published: November 2003

We investigate the canonical forms of positive partial transposition (PPT) density matrices in [Formula: see text] composite quantum systems with rank N. A general expression for these PPT states are explicitly obtained. From this canonical form a sufficient separability condition is presented.
THE 2-LOCAL HAMILTONIAN PROBLEM ENCOMPASSES NP
Authors: WOCJAN PAWEL , BETH THOMAS
Published: November 2003

We show that the NP-complete problems max cut and independent set can be formulated as the 2-local Hamiltonian problem as defined by Kitaev. The 5-local Hamiltonian problem was the first problem to be shown to be complete for the quantum complexity class QMA — the quantum analog of NP. Subsequently, it was shown that 3-locality is already sufficient for QMA-completeness. It is still not known whether the 2-local Hamiltonian problem is QMA-complete. Therefore it is interesting to determine what problems can be reduced to the 2-local Hamiltonian problem. Kitaev showed that 3-SAT can be formulated as a 3-local Hamiltonian problem. We extend his result by showing that 2-locality is sufficient in order to encompass NP.
QUANTUM SOLUTION TO THE NEWCOMB'S PARADOX
Authors: PIOTROWSKI EDWARD W. , SŁADKOWSKI JAN
Published: November 2003

We show that quantum game theory offers an interesting solution to the famous Newcomb's paradox (free-will problem). Divine foreknowledge is not necessary for a successful completion of the game because quantum theory offers a way to discern human intentions in such a way that the human retain her/his free-will but cannot profit from changing decision. Possible interpretation in terms of quantum market games is proposed.
ELEMENTS OF INFORMATION-THEORETIC DERIVATION OF THE FORMALISM OF QUANTUM THEORY
Authors: GRINBAUM ALEXEI
Published: November 2003

Information-theoretic derivations of the formalism of quantum theory have recently attracted much attention. We analyze the axioms underlying a few such derivations and propose a conceptual framework in which, by combining several approaches, one can retrieve more of the conventional quantum formalism.
Human Immunodeficiency Virus Hematology
Authors: Volberding Paul A. , Baker Kelty R. , Levine Alexandra M.
Published: November 2003

The advent of potent antiretroviral therapy has altered the expected natural history of human immunodeficiency virus (HIV) infection and of many previously associated opportunistic complications, including malignancies. At the same time, HIV suppression hasn’t affected all of these complications equally and the longer expected survival of infected patients may allow the development of newer complications. Additionally, the use of potent antiretroviral combination therapy may itself lead to hematological toxicities. Together these changes affect the consultation role of the hematology-oncology specialist in comprehensive HIV care and demand ongoing education.

In Section I, Dr. Paul Volberding reviews the biology of antiretroviral drug development and the progression in discovering new agents as the viral life cycle is further elucidated. He briefly summarizes the process of combining agents to achieve the degree of viral suppression required for long-term clinical benefit.

In Section II, Dr. Kelty Baker reviews the effects of HIV and its therapy on hematologic dyscrasia and clotting disorders. She summarizes how therapy may decrease certain previously common manifestations of HIV disease while adding new problems likely to result in referral to the hematologist. In addition, she addresses the role of secondary infections, such as parvovirus, in this spectrum of disorders.

In Section III, Dr. Alexandra Levine discusses the still challenging aspects of HIV associated non-Hodgkin’s lymphoma and the association between HIV infection and Hodgkin’s disease. She addresses current controversies in the pathogenesis of HIV related lymphomas and summarizes a number of recent trials of combination chemotherapy, with or without monoclonal antibodies, in their management. Additionally, she reviews the complex relationship of HIV disease with multicentric Castleman’s disease and recent attempts to manage this disorder.