bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do Patients Accept Implantable Atrial Defibrillation Therapy?
Authors: BURNS JASON L. , SEARS SAMUEL F. , SOTILE REBECCA , SCHWARTZMAN DAVID S. , HOYT ROBERT H. , ALVAREZ LUIS G. , UJHELYI MICHAEL R. 
Published: December 2004

Introduction: The Medtronic Jewel AF 7250 is an implantable cardioverter defibrillator with atrial and ventricular therapies (ICD‐AT). The ICD‐AT is effective in managing atrial tachyarrhythmias (atrial fibrillation [AF]), but patient acceptance remains an issue. This aim of this study was to measure ICD‐AT acceptance. Methods and Results: ICD‐AT acceptance was evaluated in 96 patients enrolled in the “Jewel AF‐AF‐Only Study” for ≥3 months of follow‐up (mean 19 months). Patients were mostly men (72%; age 65 ± 12 years). Clinical data and a written survey (75% response rate) were used to quantify demographics, AF frequency and symptoms, atrial defibrillation therapy, quality of life (QOL), psychosocial distress, and ICD‐AT therapy acceptance. From implant to survey, AF symptom and severity scores decreased by 18% (P ≤ 0.05), and QOL (SF‐36) scores increased by 15% to 50% (P ≤ 0.05). ICD‐AT therapy acceptance was high, with 71.3% of patients scoring in the 75th percentile on the Florida Patient Acceptance Survey. ICD‐AT acceptance was correlated with the Physical Component Scale and Mental Health Component Scale scores of the SF‐36 (r = 0.28 and 0.35, respectively). ICD‐AT acceptance was negatively correlated with depressive symptomatology (r =–0.59), trait anxiety (r =–0.48), illness intrusiveness (r =–0.55), and AF symptom and severity scores (r =–0.26). ICD‐AT acceptance did not correlate with preimplant cardioversions, number of atrial shocks, AF episodes detected by the device, or device implant duration. Conclusion: Most patients accepted ICD‐AT therapy. Patients were more likely to accept ICD‐AT if they had less psychosocial distress, greater QOL, and lower AF symptom burden. (J Cardiovasc Electrophysiol, Vol. 15, pp. 286‐291, March 2004)
Identification of Novel Inhibitors of Bacterial Translation Elongation Factors
Authors: Jayasekera Maithri M. K. , Onheiber Keysha , Keith John , Venkatesan Hariharan , Santillan Alejandro , Stocking Emily M. , Tang Liu , Miller Jennifer , Gomez Leslie , Rhead Brooke , Delcamp Tavner , Huang Shaoming , Wolin Ronald , Bobkova Ekaterina V. , Shaw Karen Joy 
Published: December 2004

ABSTRACT

Bacterial elongation factor Tu (EF-Tu) and EF-Ts are interacting proteins involved in polypeptide chain elongation in protein biosynthesis. A novel scintillation proximity assay for the detection of inhibitors of EF-Tu and EF-Ts, as well as the interaction between them, was developed and used in a high-throughput screen of a chemical library. Several compounds from a variety of chemical series with inhibitory properties were identified, including certain indole dipeptides, benzimidazole amidines, 2-arylbenzimidazoles, N-substituted imidazoles, and N-substituted guanidines. The in vitro activities of these compounds were confirmed in a coupled bacterial transcription-translation assay. Several indole dipeptides were identified as inhibitors of bacterial translation, with compound 2 exhibiting a 50% inhibitory concentration of 14 μM and an MIC for
S. aureus
ATCC 29213 of 5.6 μg/ml. Structure-activity relationship studies around the dipeptidic indoles generated additional analogs with low micromolar MICs for both gram-negative and gram-positive bacteria. To assess the specificity of antibacterial action, these compounds were evaluated in a metabolic labeling assay with
Staphylococcus aureus
. Inhibition of translation, as well as limited effects on other macromolecular pathways for some of the analogs studied, indicated a possible contribution from a non-target-based antibacterial mechanism of action.
Pharmacokinetics of Oritavancin in Plasma and Skin Blister Fluid following Administration of a 200-Milligram Dose for 3 Days or a Single 800-Milligram Dose
Authors: Fetterly Gerald J. , Ong Christine M. , Bhavnani Sujata M. , Loutit Jeffrey S. , Porter Steven B. , Morello Lisa G. , Ambrose Paul G. , Nicolau David P. 
Published: December 2004

ABSTRACT

Oritavancin is a novel glycopeptide currently being developed for the treatment of complicated skin and skin structure infections (cSSSI), including those caused by multidrug resistant gram-positive pathogens. The disposition of oritavancin in skin structures was investigated using a cantharide-induced blister fluid model. Seventeen healthy male subjects received oritavancin, but only 16 subjects were evaluated after one subject discontinued study drug. Each subject (eight per dose group) received 200 mg of oritavancin once a day for 3 days (group A) or 800 mg as one single dose (group B). Group A plasma samples and exudates from blister fluid were collected on days 3, 4, 7, 9, and 12 and on days 3, 4, 7, and 9, respectively. Group B samples and exudates were collected on days 1, 2, 5, 7, and 10 and on days 1, 2, 5, and 7, respectively. Drug concentrations were determined using a liquid chromatography-tandem mass spectrometry assay and, subsequently, pharmacokinetic analysis was performed. Differences between treatment groups in ratios for area under the concentration-time curve for blister fluid and plasma (AUC
blister fluid
/AUC
plasma
ratios) were evaluated using a
t
test (α = 0.05). Mean maximum concentration of drug in plasma or blister fluid was approximately 8-fold and 11-fold higher in plasma than in blister fluid following the 200- or 800-mg doses of oritavancin, respectively. Mean AUC
blister fluid
/AUC
plasma
ratios at 24 h were 0.190 (standard deviation [SD], 0.052) and 0.182 (SD, 0.062) for groups A and B, respectively (
P
= 0.791). To place these results in a clinical context, mean drug concentrations in blister fluid exceed the oritavancin MIC at which 90% of strains are inhibited of
Staphylococcus aureus
(2 μg/ml) by approximately 2- to 5.5-fold at 12 h and 1.5- to 3-fold at 24 h following administration of both dosing regimens. These results support the potential use of oritavancin for the treatment of cSSSI.
Ecological Effects of Perorally Administered Pivmecillinam on the Normal Vaginal Microflora
Authors: Sullivan Åsa , Fianu-Jonasson Aino , Landgren Britt-Marie , Nord Carl Erik 
Published: December 2004

ABSTRACT

The knowledge of the effects of antimicrobial agents on the normal vaginal microflora is limited. The objective of the present study was to study the ecological impact of pivmecillinam on the normal vaginal microflora. In 20 healthy women, the estimated day of ovulation was determined during three subsequent menstrual cycles. Microbiological and clinical examinations were performed on the estimated day of ovulation and on day 3 in all cycles and also on day 7 after ovulation in cycles 1 and 2. Anaerobic and facultative anaerobic gram-positive rods, mainly species of lactobacilli and actinomycetes, dominated the microflora. One woman was colonized on the third day of administration with a resistant
Escherichia coli
strain, and
Candida albicans
was detected in one woman on days 3 and 7 in cycle 2. No other major changes in the normal microflora occurred during the study. Administration of pivmecillinam had a minor ecological impact on the normal vaginal microflora.
Pharmacodynamic Profile of Ertapenem against
Klebsiella pneumoniae
and
Escherichia coli
in a Murine Thigh Model
Authors: Maglio Dana , Banevicius Mary Anne , Sutherland Christina , Babalola Chinedum , Nightingale Charles H. , Nicolau David P. 
Published: December 2004

ABSTRACT

The pharmacodynamic profile of ertapenem was evaluated in a neutropenic mouse thigh infection model. Extended-spectrum beta-lactamase (ESBL)-positive and ESBL-negative clinical strains of
Escherichia coli
and
Klebsiella pneumoniae
were studied. MICs ranged from 0.0078 to 0.06 μg/ml with standard inoculum tests. Ertapenem doses were administered once to five times daily to achieve various exposures, reported as the percentage of the dosing interval that the concentration of free ertapenem was in excess of the MIC (%
T
>MIC
free
). Mean values for the static exposure and 80% maximally effective exposure (ED
80
) were 19% (range, 2 to 38%) and 33% (range, 13 to 65%)
T
>MIC
free
, respectively. Differences in exposure requirements based on the presence of an ESBL resistance mechanism or bacterial species were not evident. In addition, experiments using a 100-fold higher inoculum did not decrease the magnitude of the reduction in bacterial density from baseline achieved compared to lower-inoculum studies. The pharmacodynamic parameter of %
T
>MIC
free
correlated well with bactericidal activity for all isolates, and the static and ED
80
exposures are consistent with those reported previously for carbapenems.
Pharmacodynamics of Cefepime Alone and in Combination with Various Antimicrobials against Methicillin-Resistant
Staphylococcus aureus
in an In Vitro Pharmacodynamic Infection Model
Authors: Huang Vanthida , Rybak Michael J. 
Published: December 2004

ABSTRACT

Treatment options for gram-positive resistant bacteria are limited; therefore, efforts to evaluate therapy options in the critical care population are warranted. Cefepime has broad-spectrum activity against gram-negative and gram-positive organisms. We have previously demonstrated that the combination of cefepime with vancomycin, linezolid, or quinupristin-dalfopristin had an improved or enhanced effect against methicillin-resistant
Staphylococcus aureus
(MRSA). We investigated various regimens of cefepime alone and in combination against two clinical MRSA isolates (R2481 and R2484) in an established in vitro pharmacodynamic model. Human pharmacokinetic regimen simulations were as follows: cefepime, 2 g every 8 h (q8h) (C8) and 12 h (C12), continuous-infusion 2-g loading dose followed by 4 g alone or in combination with gentamicin and tobramycin (1.0 or 2.0 [G1 and G2 or TB1 and TB2] mg/kg of body weight q12h and 5.0 [G5 or TB5] mg/kg q24h), arbekacin (ARB) (100 mg q12h), linezolid (LIN) (600 mg q12h), tigecycline (TIG) (100 mg q24h), or daptomycin (DAP) (6 mg/kg q24h) for 48 h. The MICs for cefepime, gentamicin, tobramycin, ARB, LIN, TIG, and DAP for the two clinical MRSA isolates (R2481 and R2484) were 4 and 4, 0.25 and 0.5, 128 and 0.5, 0.5 and 0.125, 2 and 4, 0.25 and 0.25, and 0.0625 and 0.125 μg/ml, respectively. At 48 h, combinations of C12 and C8 plus ARB, G1, or G5 (range, −2.05- to −4.32-log
10
decrease) demonstrated enhanced lethality against R2481 (resistant to tobramycin) (
P
< 0.05). A similar relationship was demonstrated against R2484 with cefepime plus ARB, gentamicin, or tobramycin (range, −2.05- to −3.63-log
10
decrease) (
P
< 0.05). A 99.9% kill was achieved with cefepime plus aminoglycoside combinations as early as 2 h and maintained throughout the 48-h period. TIG was antagonistic when combined with C12 against both isolates. DAP alone achieved 99.9% kill for up to 48 h for both isolates and was the most active agent against R2481 and R2484 (−2.89- and −3.61-log
10
decrease at 48 h); therefore, combination therapy did not enhance lethality. Overall, the most potent combinations noted were cefepime in combination with low- and high-dose aminoglycosides. Further investigations with combination therapies are warranted.
Single-Dose Safety and Pharmacokinetics of Amprenavir (141W94), a Human Immunodeficiency Virus Type 1 (HIV-1) Protease Inhibitor, in HIV-Infected Children
Authors: Yogev Ram , Kovacs Andrea , Chadwick Ellen G. , Homans James D. , Lou Yu , Symonds William T. 
Published: December 2004

ABSTRACT

A phase I, open-label, dose-escalating trial was conducted to evaluate the safety, tolerability, and pharmacokinetics of single, oral doses of amprenavir (141W94), a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) protease, in 20 HIV-infected children 4 to 12 years of age. The doses of amprenavir evaluated, 5, 10, 15, and 20 mg/kg of body weight, were comparable to those evaluated in adult phase I and II studies. The most common clinical adverse event associated with amprenavir, administered as soft gelatin capsules, was nausea. Amprenavir was rapidly absorbed, with a mean time to maximum concentration (
T
max
) occurring 0.95 to 1.58 h after dosing. The area under the concentration-time curve (AUC
0
→
∞
) was dose proportional, and the mean maximum plasma concentration (
C
max
) increased linearly in a less than dose-proportional manner. Amprenavir was eliminated relatively slowly, with a mean terminal-phase half-life (
t
1/2
) of 6.17 to 8.28 h. The
t
1/2
, apparent total clearance, and apparent volume of distribution during the elimination phase were dose independent. Considerable interpatient variability was seen for all pharmacokinetic parameters of amprenavir. The results of this study suggest that 20 mg of amprenavir/kg administered twice a day should be used in future pediatric studies.
Emergence of CTX-M-15-Producing Enterobacteria in Cameroon and Characterization of a
bla
CTX-M-15
-Carrying Element
Authors: Gangoue-Pieboji J. , Miriagou V. , Vourli S. , Tzelepi E. , Ngassam P. , Tzouvelekis L. S. 
Published: December 2004

ABSTRACT

CTX-M-15-producing
Klebsiella pneumoniae
and
Escherichia coli
emerged recently in Cameroon. CTX-M-15 was encoded by two different multiresistance plasmids, of which one carried an IS
Ecp1
-
bla
CTX-M-15
element flanked by a 5-bp target site duplication and inserted within a Tn
2
-derived sequence. A truncated form of this element in the second plasmid was identified.
Detection and Quantification of Macrolide Resistance Mutations at Positions 2058 and 2059 of the 23S rRNA Gene by Pyrosequencing
Authors: Haanperä Marjo , Huovinen Pentti , Jalava Jari 
Published: December 2004

ABSTRACT

A pyrosequencing method for detection and quantification of macrolide resistance mutations at positions 2058 and 2059 (
Escherichia coli
numbering) of the 23S rRNA gene is described. The method was developed and tested for
Streptococcus pneumoniae
,
Streptococcus pyogenes
,
Mycobacterium avium
,
Campylobacter jejuni
, and
Haemophilus influenzae
.
Pharmacodynamic Evaluation of Extending the Administration Time of Meropenem using a Monte Carlo Simulation
Authors: Lomaestro Ben M. , Drusano G. L. 
Published: December 2004

ABSTRACT

A Monte Carlo simulation demonstrated that 1 g of meropenem (MEM) every 8 h (q8h) (3-h infusion) has a higher target attainment rate against
Pseudomonas aeruginosa
than either 500 mg of MEM q8h (3-h infusion) or 0.5 g of imipenem-cilastatin (I-C) q6h (1-h infusion). For other pathogens, 500 mg of MEM q8h was equivalent or superior to I-C.
A Mutant of Staphylococcal Enterotoxin C Devoid of Bacterial Superantigenic Activity Elicits a Th2 Immune Response for Protection againstStaphylococcus aureusInfection
Authors: Hu Dong-Liang , Cui Jing-Chun , Omoe Katsuhiko , Sashinami Hiroshi , Yokomizo Yuichi , Shinagawa Kunihiro , Nakane Akio 
Published: December 2004

ABSTRACTStaphylococcal enterotoxin C (SEC), a bacterial superantigenic exotoxin, is commonly produced by invasiveStaphylococcus aureusisolates, especially methicillin-resistant strains and isolates from animal diseases. We constructed and expressed a nontoxic mutant SEC (mSEC) and investigated whether immunization with mSEC, which is devoid of superantigenic activity, can protect againstS. aureusinfection. Mice were immunized with mSEC and challenged with viableS. aureus. The bacterial counts in the organs of mSEC-immunized mice were significantly lower and the survival rate was higher than the corresponding values for the control group. Immunization with mSEC strongly induced the production of T-helper 2 type antibodies, immunoglobulin G1, and immunoglobulin G2b. The production of interleukin-10 (IL-10) and IL-4 was significantly greater in immunized mice challenged withS. aureusthan in the control mice, whereas the production of gamma interferon (IFN-γ) was significantly decreased in the immunized mice. The cytokine response in a spleen cell culture that was stimulated with heat-killedS. aureusor SEC showed that immunization with mSEC inhibited IFN-γ production and up-regulated IL-10 production in vitro. Furthermore, IFN-γ and tumor necrosis factor alpha production in vitro was significantly inhibited by sera from mSEC-immunized mice but not by sera from control mice. These results suggest that immunization with mSEC devoid of superantigenic properties provides protection againstS. aureusinfection and that the protection might be mediated by SEC-specific neutralizing antibodies.
Trigger Factor inStreptococcus mutansIs Involved in Stress Tolerance, Competence Development, and Biofilm Formation
Authors: Wen Zezhang T. , Suntharaligham Prashanth , Cvitkovitch Dennis G. , Burne Robert A. 
Published: December 2004

ABSTRACTTrigger factor is a ribosome-associated peptidyl-prolylcis/transisomerase that is highly conserved in most bacteria. A gene, designatedropA, encoding an apparent trigger factor homologue, was identified inStreptococcus mutans, the primary etiological agent of human dental caries. Inactivation ofropAhad no major impact on growth rate in planktonic cultures under the conditions tested, although the RopA-deficient mutant formed long chains in broth. Deficiency of RopA decreased tolerance to acid killing and to oxidative stresses induced by hydrogen peroxide and paraquat, and it reduced transformation efficiency about 200-fold. Addition of synthetic competence-stimulating peptide to the culture medium enhanced transformability of both the mutant and wild-type strains, although theropAstrain did not attain levels of competence observed for the parent. Loss of RopA decreased the capacity ofS. mutansto form biofilms by over 80% when cultivated in glucose, but it increased biofilm formation by over 50% when sucrose was provided as the carbohydrate source. Western blot analysis revealed that the expression of glucosyltransferases B and D was lower in the RopA-deficient mutant. These results suggest that RopA is a key regulator of acid and oxidative stress tolerance, genetic competence, and biofilm formation, all critical virulence properties ofS. mutans.
Both Innate Immunity and Type 1 Humoral Immunity toStreptococcus pneumoniaeAre Mediated by MyD88 but Differ in Their Relative Levels of Dependence on Toll-Like Receptor 2
Authors: Khan Abdul Q. , Chen Quanyi , Wu Zheng-Qi , Paton James C. , Snapper Clifford M. 
Published: December 2004

ABSTRACTLittle is known regarding the role of Toll-like receptors (TLRs) in regulating protein- and polysaccharide-specific immunoglobulin (Ig) isotype production in response to an in vivo challenge with an extracellular bacterium. In this report we demonstrate that MyD88−/−, but not TLR2−/−, mice are markedly defective in their induction of multiple splenic proinflammatory cytokine- and chemokine-specific mRNAs after intraperitoneal (i.p.) challenge with heat-killedStreptococcus pneumoniaecapsular type 14 (S. pneumoniaetype 14). This is correlated with analogous responses in splenic cytokine protein release in vitro following addition ofS. pneumoniaetype 14. Consistent with these data, naïve MyD88−/−, but not TLR2−/−, mice are more sensitive to killing following i.p. challenge with liveS. pneumoniaetype 14, relative to responses in wild-type mice. However, prior immunization of MyD88−/−mice with heat-killedS. pneumoniaetype 14 protects against an otherwise-lethal challenge with liveS. pneumoniaetype 14. Surprisingly, both MyD88−/−and TLR2−/−mice exhibit striking and equivalent defects in elicitation of type 1 IgG isotypes (IgG3, IgG2b, and IgG2a), but not the type 2 IgG isotype, IgG1, specific for several protein and polysaccharide antigens, in response to i.p. challenge with heat-killedS. pneumoniaetype 14. Of note, the type 1 IgG isotype titers specific for pneumococcal surface protein A are reduced in MyD88−/−mice but not TLR2−/−mice. These data suggest that distinct TLRs may differentially regulate innate versus adaptive humoral immunity to intactS. pneumoniaeand are the first to implicate a role for TLR2 in shaping an in vivo type 1 IgG humoral immune response to a gram-positive extracellular bacterium.
Enhanced Immunoglobulin A Response and Protection againstSalmonella entericaSerovar Typhimurium in the Absence of the Substance P Receptor
Authors: Walters Nancy , Trunkle Theresa , Sura Michael , Pascual David W. 
Published: December 2004

ABSTRACTThe development of the neurokinin-1 receptor-deficient (NK1R−/−) mouse permitted inquiry into the regulation of secretory immunoglobulin A (S-IgA) responses by substance P (SP) after oral immunization with aSalmonella entericaserovar Typhimurium vector expressing colonization factor antigen I (CFA/I) from enterotoxigenicEscherichia coli. In NK1R−/−mice, mucosal and serum IgA anti-CFA/I fimbrial responses were augmented, while secreted IgG anti-CFA/I fimbrial responses remained unaffected compared to those of BALB/c (NK1R+/+) mice. Supportive antibody-forming cells were present in the small intestinal lamina propria and spleen. To gain insight as to why the augmented S-IgA responses occurred, minimally, the responses were not attributed to differences in vaccine colonization of Peyer's patch (PP) and spleen or in their respective tissue weights. However, these S-IgA responses were supported by increased numbers of PP CD4+T helper (Th) cells secreting interleukin-5 (IL-5) and IL-6 and splenic CD4+Th cells secreting IL-6 compared to NK1R+/+mice. Challenge of naive NK1R−/−mice with wild-typeSalmonellashowed improved median survival compared to naive NK1R+/+mice. Data from peritoneal macrophage infection studies suggest that this survival is in part contributed by increased IL-10 production. Oral vaccination withSalmonellaCFA/I orSalmonellavector showed no significant differences in conferred protection against wild-type challenge for either NK1R−/−or NK1R+/+mice. Thus, these studies suggest that SP mediation contributes to proinflammatory responses toSalmonellainfections.
The Cytolethal Distending Toxin Induces Receptor Activator of NF-κB Ligand Expression in Human Gingival Fibroblasts and Periodontal Ligament Cells
Authors: Belibasakis G. N. , Johansson A. , Wang Y. , Chen C. , Kalfas S. , Lerner U. H. 
Published: December 2004

ABSTRACTActinobacillus actinomycetemcomitansis associated with localized aggressive periodontitis, a disease characterized by rapid loss of the alveolar bone surrounding the teeth. Receptor activator of NF-κB Ligand (RANKL) and osteoprotegerin (OPG) are two molecules that regulate osteoclast formation and bone resorption. RANKL induces osteoclast differentiation and activation, whereas OPG blocks this process by acting as a decoy receptor for RANKL. The purpose of this study was to investigate the effect ofA. actinomycetemcomitanson the expression of RANKL and OPG in human gingival fibroblasts and periodontal ligament cells. RANKL mRNA expression was induced in both cell types challenged byA. actinomycetemcomitansextract, whereas OPG mRNA expression remained unaffected. Cell surface RANKL protein was also induced byA. actinomycetemcomitans, whereas there was no change in OPG protein secretion. A cytolethal distending toxin (Cdt) gene-knockout strain ofA. actinomycetemcomitansdid not induce RANKL expression, in contrast to its wild-type strain. Purified Cdt fromHaemophilus ducreyialone, or in combination with extract from theA. actinomycetemcomitans cdtmutant strain, induced RANKL expression. Pretreatment ofA. actinomycetemcomitanswild-type extract with Cdt antiserum abolished RANKL expression. In conclusion,A. actinomycetemcomitansinduces RANKL expression in periodontal connective tissue cells. Cdt is crucial for this induction and may therefore be involved in the pathological bone resorption during the process of localized aggressive periodontitis.