bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and Biomechanical Efficacies of Mechanical Perturbation Training After Anterior Cruciate Ligament Rupture
Authors: Nawasreh Zakariya , Logerstedt David , Marmon Adam , Snyder-Mackler Lynn 
Published: October 2018

Context: Manual perturbation training improves knee functional performance and mitigates abnormal gait in patients with anterior cruciate ligament (ACL) rupture. However, manual perturbation training is time- and labor-intensive for therapists. Objective: To investigate whether perturbation training administered using a mechanical device can provide effects similar to manual training on clinical measures and knee biomechanics after ACL rupture. Design: Prospective cohort (therapeutic) study. A 2 × 2 analysis of variance was used for statistical analysis. Setting: A clinical and biomechanical laboratory. Patients: Eighteen level I/II patients with acute ACL ruptures participated in this preliminary study. Intervention: Nine patients received mechanical perturbation training on an automated mechanical device (mechanical group), and 9 patients received manual perturbation training (manual group). Outcome Measures: Patients completed performance-based testing (quadriceps strength and single-legged hop tests), patient-reported questionnaires (Knee Outcome Survey-Activities of Daily Living Scale, Global Rating Score, and International Knee Documentation Committee 2000), and 3-dimensional gait analysis before (pretesting) and after (posttesting) training. Results: There was no significant group-by-time interaction found for all measures (P ≥ .18). Main effects of time were found for International Knee Documentation Committee 2000 (pretesting: 69.10 [10.95], posttesting: 75.14 [7.19]), knee excursion during weight-acceptance (pretesting: 16.01° [3.99°]; posttesting: 17.28° [3.99°]) and midstance (pretesting: 14.78° [4.13°]; posttesting: 16.92° [4.53°]) and external knee-flexion moment (pretesting: 0.43 [0.11] N m/kg/m; posttesting: 0.48 [0.11] N m/kg/m) (P ≤ .04). After accounting for pretesting groups’ differences, the mechanical group scored significantly higher on triple hops (mechanical: 96.73% [6.65%]; manual: 84.97% [6.83%]) and 6-m timed hops (mechanical: 102.07% [9.50%]; manual: 91.21 [9.42%]) (P ≤ .047) compared with manual group. Conclusion: The clinical significance of this study is the mechanical perturbation training produced effects similar to manual training, with both training methods were equally effective at improving patients’ perception of knee function and increasing knee excursion and external flexion moment during walking after acute ACL rupture. Mechanical perturbation training is a potential treatment to improve patients’ functional and biomechanical outcomes after ACL rupture.
Decreased Susceptibilities to Teicoplanin and Vancomycin among Coagulase-Negative Methicillin-Resistant Clinical Isolates of Staphylococci
Authors: Sieradzki Krzysztof , Villari Paolo , Tomasz Alexander 
Published: October 2018

ABSTRACT

Of 41 methicillin-resistant coagulase-negative staphylococcal clinical isolates collected during a 5-month period between late 1995 and early 1996, 28 showed tube dilution teicoplanin MICs of 4 to 8 μg/ml which increased to 16 to 32 μg/ml upon prolonged incubation. Cultures of such bacteria were heterogeneous; they contained subpopulations with frequencies of 10
−5
to 10
−4
that could grow on up to 50 μg of teicoplanin per ml. The same cultures were also heterogeneous with respect to susceptibility to vancomycin; while the MICs for the majority of cells were 2 to 4 μg/ml, subpopulations that could grow on 6 to 12 μg of vancomycin per ml were also present at frequencies of 10
−5
to 10
−7
. Selective enrichment of such cultures for the resistant subpopulation occurred with relative ease under laboratory conditions. Heterogeneous phenotypes for teicoplanin (but not for vancomycin) susceptibility were also identified in several
Staphylococcus epidermidis
isolates collected during the preantibiotic era. The addition of half the MIC of teicoplanin inhibited autolysis and caused formation of cellular aggregates which disintegrated to individual bacteria in the stationary phase when the titer of teicoplanin in the medium fell to undetectable levels, indicating removal of the antibiotic from the culture medium by the bacteria.
Emergence of
Mycobacterium avium
Populations Resistant to Macrolides during Experimental Chemotherapy
Authors: Bermudez Luiz E. , Petrofsky Mary , Kolonoski Peter , Young Lowell S. 
Published: October 2018

ABSTRACT

Macrolide resistance is an emerging problem in AIDS patients who receive these agents for treatment or prophylaxis against
Mycobacterium avium
(MAC) infection. We compared the emergence of resistant MAC strains during therapy with clarithromycin (clarithromycin resistance was defined as MIC ≥ 32 μg/ml) and azithromycin (azithromycin resistance was defined as MIC ≥ 128 μg/ml) in C57BL/6 beige mice. Treatment with clarithromycin and azithromycin resulted in a decrease of 98.5% in the number of viable bacteria in spleens at week 8 and 99% at week 12 compared with the number of bacteria present in spleen before the initiation of therapy (
P
< 0.001). Splenic homogenates were also plated onto 7H11 agar plus clarithromycin at 32 μg/ml or azithromycin at 128 μg/ml. Resistance emerged significantly more often in mice treated with clarithromycin (100% of treated mice at both 8 and 12 weeks) than in those receiving azithromycin (0% at week 8 and 14% at week 12). The frequencies of resistance of the MAC population in the spleen to clarithromycin were 2.1 × 10
−3
at week 8 and 1.1 × 10
−2
at week 12, whereas resistance to azithromycin was absent at week 8 (all mice) and was ∼3.5 × 10
−5
(mean for the three positive animals) at week 12. Clarithromycin was more effective in initial reduction of MAC burden in tissue after 8 and 12 weeks of treatment, but resistant strains emerged significantly more frequently after treatment with clarithromycin than after treatment with azithromycin.
Concentrations of Cefpirome in Cerebrospinal Fluid of Children with Bacterial Meningitis after a Single Intravenous Dose
Authors: Friedland Ian R. , Sultan Eric , Lehr Karl H. , Lenfant Bernard 
Published: October 2018

ABSTRACT

A single intravenous dose of cefpirome, 50 mg/kg, was administered to 15 children with bacterial meningitis 24 to 48 h after initiation of standard antibiotic and steroid therapy. Cefpirome concentrations in serum and cerebrospinal fluid were determined at selected time intervals. The mean (standard deviation) peak concentration in cerebrospinal fluid (
n
= 5) was 10.8 (7.8) μg/ml. Drug concentrations in cerebrospinal fluid above the MIC for
Streptococcus pneumoniae
at which 90% of the isolates were inhibited were found 2, 4, and 8 h after the dose of cefpirome was given. The penetration of cefpirome into cerebrospinal fluid compares favorably with that of other extended-spectrum cephalosporins and suggests that this agent would be useful in the therapy of childhood meningitis, including cases caused by drug-resistant
S. pneumoniae.
Epidemiology and Successful Control of a Large Outbreak Due to
Klebsiella pneumoniae
Producing ExtendedSpectrum β-Lactamases
Authors: Peña Carmen , Pujol Miquel , Ardanuy Carmen , Ricart Asumpta , Pallares Roman , Liñares Josefina , Ariza Javier , Gudiol Francisco 
Published: October 2018

ABSTRACT

An outbreak due to extended-spectrum β-lactamase-producing
Klebsiella pneumoniae
(ESBL-KP) was detected from May 1993 to June 1995. A total of 145 patients, particularly patients in intensive care units (ICUs) (107 patients [72%]), were colonized or infected. Infection developed in 92 (63%) patients, and primary bacteremia caused by ESBL-KP was the most frequent infection (40 of 92 patients [43%]). A single clone of ESBL-KP was identified by pulsed-field gel electrophoresis analysis throughout the whole period, and no molecular epidemiological relationship could be found between the epidemic strain and non-ESBL-KP isolates. To determine risk factors for ESBL-KP infection weekly rectal swabs were obtained in three serial incidence surveys (470 patients); the probabilities of carriage of ESBL-KP in the digestive tract were 33% (October and November 1993), 40% (May and June 1994), and 0% (October and November 1995) at 10 days of ICU admission. A logistic regression model identified prior carriage of ESBL-KP in the digestive tract (odds ratio, 3.4; 95% confidence interval 1.1 to 10.4) as an independent variable associated with ESBL-KP infection. A statistically significant correlation was observed between the restricted use of oxyimino-β-lactams (189 defined daily doses [DDD]/1,000 patient-days to 24 DDD/1,000 patient-days) and the trends of ESBL-KP infection (
r
= 0.7;
P
= 0.03).
Restoration of Immune Response by a Cationic Amphiphilic Drug (AY 9944) In Vitro: A New Approach To Chemotherapy against Human Immunodeficiency Virus Type 1
Authors: Achour Ammar , Landureau Jean-Charles , Salerno-Concalves Rosangela , Mazière Jean-Claude , Zagury Daniel 
Published: October 2018

ABSTRACTAY 9944 [AY;trans-1,4-bis(chlorobenzylaminomethyl)-cyclohexane dihydrochloride], an inhibitor of sterol synthesis, was found to help restore the normal mitogenic responses and cytokine profiles of peripheral mononuclear cells (PBMCs) from AIDS patients in vitro. Compared to untreated cells, the human immunodeficiency virus type 1 (HIV-1)-infected PBMCs precultured in the presence of AY exhibited a normal rate of either mitogen-induced or recall- and superantigen-induced proliferation. After 2 weeks in the presence of the drug, the percentage of dead CD4+cells in HIV-1-infected cultures was comparable to that observed in uninfected cultures, while over the same time interval it increased by three- to fivefold in HIV-1-infected cultures maintained in the absence of AY. AY also stimulated by 2- to 12-fold interleukin-12 (IL-12) and (gamma interferon production. For IL-12, this effect appears to be related to an increase in corresponding IL-12 p35 and IL-12 p40 mRNA levels. Moreover, AY restored the expression of the IL-2 receptor, which was severely impaired in HIV-1-infected PBMCs. Although the drug has no direct antiviral effect (it does not significantly inhibit reverse transcriptase activity measured in vitro), it might be considered a potential therapeutic agent for HIV-infected patients, in that it may correct viral infection-related immune system defects by indirectly enhancing the level of resistance to HIV and opportunistic infections.
In Vitro Antifungal Activities of a Series of Dication-Substituted Carbazoles, Furans, and Benzimidazoles
Authors: Del Poeta Maurizio , Schell Wiley A. , Dykstra Christine C. , Jones Susan K. , Tidwell Richard R. , Kumar Arvind , Boykin David W. , Perfect John R. 
Published: October 2018

ABSTRACT

Aromatic dicationic compounds possess antimicrobial activity against a wide range of eucaryotic pathogens, and in the present study an examination of the structures-functions of a series of compounds against fungi was performed. Sixty-seven dicationic molecules were screened for their inhibitory and fungicidal activities against
Candida albicans
and
Cryptococcus neoformans
. The MICs of a large number of compounds were comparable to those of the standard antifungal drugs amphotericin B and fluconazole. Unlike fluconazole, potent inhibitory compounds in this series were found to have excellent fungicidal activities. The MIC of one of the most potent compounds against
C. albicans
was 0.39 μg/ml, and it was the most potent compound against
C. neoformans
(MIC, ≤0.09 μg/ml). Selected compounds were also found to be active against
Aspergillus fumigatus
,
Fusarium solani
,
Candida
species other than
C. albicans
, and fluconazole-resistant strains of
C. albicans
and
C. neoformans
. Since some of these compounds have been safely given to animals, these classes of molecules have the potential to be developed as antifungal agents.
Reduction by Cefodizime of the Pulmonary Inflammatory Response Induced by Heat-Killed
Streptococcus pneumoniae
in Mice
Authors: Bergeron Yves , Ouellet Nathalie , Deslauriers Anne-Marie , Simard Marie , Olivier Martin , Bergeron Michel G. 
Published: October 2018

ABSTRACT

It has recently become apparent that overwhelming inflammatory reactions contribute to the high mortality rate associated with pneumococcal infection in immunocompetent hosts. Cefodizime (CEF) is an antibiotic that seems to be endowed with immunomodulating properties. To investigate the influence of CEF on the pulmonary inflammatory response induced by
Streptococcus pneumoniae
, we infected mice with repeated intranasal inoculations of 10
7
CFU of heat-killed fluorescein isothiocyanate-labeled bacteria, which are insensitive to the killing properties of the drug. CEF downregulated but did not abolish the strong polymorphonuclear leukocyte (PMN) recruitment induced by
S. pneumoniae
. PMN recruitment was not primarily mediated by leukotriene B
4
in this model. The drug did not interfere with intrinsic mechanisms of phagocytosis by PMNs and alveolar macrophages. CEF totally abrogated the pneumococcus-induced tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) secretion in bronchoalveolar lavage fluid. The drug also prevented IL-6 release in lung homogenates and partly inhibited TNF-α, but it did not interfere with IL-1α secretion in the lungs of infected mice. The fractional and selective downregulation of inflammatory cells and cytokines by CEF suggests cell-specific and intracellular specific mechanisms of interaction of the drug. The immunomodulatory properties of CEF may help restrain excessive inflammatory reactions, thus contributing to the reported good clinical efficacy of the drug against lower respiratory tract infections.
Comparison of Inhibitory and Bactericidal Activities and Postantibiotic Effects of LY333328 and Ampicillin Used Singly and in Combination against Vancomycin-Resistant
Enterococcus faecium
Authors: Baltch Aldona L. , Smith Raymond P. , Ritz William J. , Bopp Lawrence H. 
Published: October 2018

ABSTRACT

One hundred ninety-five individual vancomycin-resistant
Enterococcus faecium
(VRE) isolates from five upstate New York hospitals were studied for antimicrobial susceptibilities to LY333328, quinupristin-dalfopristin, teicoplanin, ampicillin, and gentamicin. LY333328 was the most active antibiotic against VRE. The effect of media and methods on the antibacterial activity of LY333328, its synergy with ampicillin, and the postantibiotic effects (PAE) of LY333328 and ampicillin were evaluated. In microdilution tests, the MIC of LY333328 at which 90% of the isolates were inhibited (MIC
90
) was 2 μg/ml in Mueller-Hinton II (MH II) broth and 1 μg/ml in brain heart infusion (BHI) broth. In contrast, on MH II agar the MIC
90
was 4 μg/ml and on BHI agar it was >16 μg/ml. Bactericidal activity was observed for most strains at concentrations from 8 to ≥133 times the MIC of the tube macrodilution in MH II broth. A bactericidal effect of LY333328 plus ampicillin was demonstrated in time-kill studies, but there was great strain-to-strain variability. By the MH II agar dilution method, bacteristatic synergy (defined as a fractional inhibitory concentration of <0.5) with LY333328 and ampicillin was demonstrated for 61% of the strains tested. Under similar conditions, there was synergy with LY333328 and quinupristin-dalfopristin or gentamicin for 27 and 15% of the strains tested, respectively. The PAE of LY333328 was prolonged (23.0 h at 10 times the MIC). However, 50% normal pooled human serum decreased the PAE to 12.2 h at 10 times the MIC. Test conditions and media had a considerable effect on VRE susceptibilities to LY333328. The prolonged PAE of LY333328, a potent new bactericidal glycopeptide, and its synergy with ampicillin in a large proportion of strains suggest that further evaluation of this drug in pharmacokinetic studies and experimental infections, including those with VRE, is warranted.
Roles of Amino Acids 161 to 179 in the PSE-4 Ω Loop in Substrate Specificity and in Resistance to Ceftazidime
Authors: Therrien Christian , Sanschagrin Francois , Palzkill Timothy , Levesque Roger C. 
Published: October 2018

ABSTRACT
The PSE-4 enzyme is a prototype carbenicillin-hydrolyzing enzyme exhibiting high activity against penicillins and early cephalosporins. To understand the mechanism that modulates substrate profiles and to verify the ability of PSE-4 to extend its substrate specificity toward expanded-spectrum cephalosporins, we used random replacement mutagenesis to generate six random libraries from amino acids 162 to 179 in the Ω loop. This region is known from studies with TEM-1 to be implicated in substrate specificity. It was found that the mechanism modulating ceftazidime hydrolysis in PSE-4 was different from that in TEM-1. The specificity of class 2c carbenicillin-hydrolyzing enzymes could not be assigned to the Ω loop of PSE-4. Analysis of the percentage of functional enzymes revealed that the hydrolysis of ampicillin was more affected than hydrolysis of carbenicillin by amino acid substitutions at positions 162 to 164 and 165 to 167.
Targeted Antimicrobial Photochemotherapy
Authors: Soukos Nikolaos S. , Ximenez-Fyvie Laurie Ann , Hamblin Michael R. , Socransky Sigmund S. , Hasan Tayyaba 
Published: October 2018

ABSTRACT

This study explores a new approach for antimicrobial therapy with light activation of targeted poly-
l
-lysine (pL)–chlorin
e6
(c

e6

) conjugates. The goal was to test the hypothesis that these conjugates between pL and c

e6

would efficiently target photodestruction towards gram-positive (
Actinomyces viscosus
) and gram-negative (
Porphyromonas gingivalis
) oral species while sparing an oral epithelial cell line (HCPC-1). Conjugates of c

e6

with pL (average molecular weight, 2,000) having a positive, neutral, or negative charge were prepared. Illumination with red light (λ
max
= 671 nm) from a diode array produced a dose-dependent loss of CFU from the bacteria, under conditions that did not affect the viability of the epithelial cells. For
P. gingivalis
, the cationic conjugate produced 99% killing, while the neutral conjugate killed 91% and the anionic conjugate killed 76% after 1 min of incubation and exposure to red light for 10 min. For
A. viscosus
, the cationic conjugate produced >99.99% killing while HCPC-1 cells remained intact. The importance of the positive charge was shown by the effectiveness of c

e6

-monoethylenediamine monoamide (a monocationic derivative of c

e6

) in killing both bacteria. The clinically employed benzoporphyrin derivative under the same conditions killed epithelial cells while leaving
P. gingivalis
relatively unharmed. A mixture of c

e6

with pL did not show phototoxicity comparable with that of the cationic conjugate. These results were explained by the selective uptake of the conjugates by bacteria (20- to 100-fold) compared to that by mammalian cells, while free c

e6

showed much less selectivity for bacteria (5- to 20-fold). The data suggest that the cationic pL-c

e6

conjugate may have an application for the photodynamic therapy of periodontal disease.
Stability of Cephalosporin Prodrug Esters in Human Intestinal Juice: Implications for Oral Bioavailability
Authors: Stoeckel Klaus , Hofheinz Werner , Laneury Jean Paul , Duchene Patrick , Shedlofsky Steve , Blouin Robert A. 
Published: October 2018

ABSTRACT

The levels of degradation of cefetamet pivoxil (CAT), cefuroxime axetil (CAE), and cefpodoxime proxetil (CPD) in 0.6 M phosphate buffer (pH 7.4) and human intestinal juice (pH 7.4) at 37°C over 24 h were compared. Significant differences in the time courses of degradation and in the patterns of degradation products were observed. (i) The relative proportions of the Δ2- and Δ3-cephalosporins were roughly reversed in the two incubation media. In phosphate buffer, the major degradation product was the Δ2-cephalosporin (CAT = 61%; CAE = 74%; CPD = 85%), while in intestinal juice it was the Δ3-cephalosporin (CAT = 86%; CAE = 75%; CPD = 87%). (ii) Generally, the degradation of the prodrug esters progressed faster in intestinal juice than in phosphate buffer (e.g., for CAT the half-lives [
t
1/2
s] were 0.78 and 4.3 h, respectively). (iii) The two diastereoisomers of CAE and CPD were degraded at different rates in intestinal juice (for the CAE diasteroisomers,
t
1/2
s = 0.37 and 0.93 h; for the CPD diastereoisomers,
t
1/2
s = 0.18 and 0.98 h) but were degraded at similar rates in phosphate buffer (for the CAE diastereoisomers,
t
1/2
= 1.6 h; for the CPD
t
1/2
diastereoisomers, = 2.2 h). It is concluded that (i) the Δ2 isomerization does not significantly affect the bioavailability of prodrug esters since enzymatic hydrolysis in the intestinal fluid proceeds mainly to the active Δ3-cephalosporin and (ii) the high degree of stereoselectivity of the enzymatic ester hydrolysis should make it possible to increase the bioavailabilities of certain prodrug esters (CAE, CPD) by using the more stable diasterioisomer.
Genotypic and Phenotypic Characterization of Human Immunodeficiency Virus Type 1 Variants Isolated from Patients Treated with the Protease Inhibitor Nelfinavir
Authors: Patick A. K. , Duran M. , Cao Y. , Shugarts D. , Keller M. R. , Mazabel E. , Knowles M. , Chapman S. , Kuritzkes D. R. , Markowitz M. 
Published: October 2018

ABSTRACT
Nelfinavir mesylate (formerly AG1343) is a potent and selective inhibitor of human immunodeficiency virus (HIV) protease approved for the treatment of individuals infected with HIV. Nucleotide sequence analysis of protease genes from plasma HIV type 1 (HIV-1) RNA revealed a unique aspartic acid (D)-to-asparagine (N) substitution at residue 30 (D30N) in 25 of 55 patients treated with nelfinavir for a median of 13 weeks. Although the appearance of D30N was occasionally associated with concurrent or sequential emergence of other changes (e.g., at residues 35, 36, 46, 71, 77, and 88), genotypic changes associated with phenotypic resistance to other protease inhibitors were not observed (e.g., at residues 48, 50, 82, and 84) or were only rarely observed (e.g., at residue 90). In phenotypic assays, viral isolates with high-level resistance to nelfinavir remained susceptible to indinavir, saquinavir, ritonavir, and amprenavir (formerly VX-478/141W94). Similar results were observed in phenotypic assays utilizing HIV-1 NL4-3, which contained the D30N substitution alone or in combination with substitutions at other residues (e.g., residues 46, 71, and 88). These data indicate that the initial pathway of resistance to nelfinavir is unique and suggest that individuals failing short courses of nelfinavir-containing regimens may respond to regimens containing other protease inhibitors.
Translation Elongation Factor 2 Is Part of the Target for a New Family of Antifungals
Authors: Capa Laura , Mendoza Alfonso , Lavandera José L. , Gómez de las Heras Federico , García-Bustos José F. 
Published: October 2018

ABSTRACT

Translation elongation factor 2 (EF2), which in
Saccharomyces cerevisiae
is expressed from the
EFT1
and
EFT2
genes, has been found to be targeted by a new family of highly specific antifungal compounds derived from the natural product sordarin. Two complementation groups of mutants resistant to the semisynthetic sordarin derivative GM193663 were found. The major one (21 members) consisted of isolates with mutations on
EFT2
. The minor one (four isolates) is currently being characterized but it is already known that resistance in this group is not due to mutations on
EFT1
, pointing to the complex structure of the functional target for these compounds. Mutations on EF2 clustered, forming a possible drug binding pocket on a three-dimensional model of EF2, and mutant cell extracts lost the capacity to bind to the inhibitors. This new family of antifungals holds the promise to be a much needed and potent addition to current antimicrobial treatments, as well as a useful tool for dissection of the elongation process in ribosomal protein synthesis.