bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre‐ and Postoperative Force Plate Analysis of Dogs with Experimentally Transected Cranial Cruciate Ligaments Treated Using Tibial Plateau Leveling Osteotomy
Authors: Ballagas Antonio J. , Montgomery Ronald D. , Henderson Ralph A. , Gillette Robert 
Published: February 2004

Objective—Quantitative and objective assessment of hindlimb kinetics after cranial cruciate ligament (CrCL) transection and subsequent stifle stabilization using the tibial plateau leveling osteotomy (TPLO) in normal dogs.Study Design—In vivo experimental biomechanical evaluation.Animals—Six healthy adult foxhounds.Methods—Dogs were screened by orthopedic and radiographic examination before study entry. Force plate analysis of gait was measured before extirpation of the right CrCL and TPLO and again at 8 and 18 weeks after surgery.Results—There was a significant decrease in peak vertical forces (PVFs) and vertical impulse (VI) of the treated hindlimb at 8 weeks when compared with preoperative and 18‐week measurements. When compared with preoperative values, there was no significant difference in 18 week PVF and VI in dogs that had TPLO.Conclusion—TPLO can restore kinetic measures of limb function at 18‐weeks after surgery when compared with preoperative values after experimental transection of the CrCL in dogs.Clinical Relevance—TPLO induces lameness that returns to near normal at 18 weeks. The severity and duration of lameness was similar to that reported for other experimental models of stifle instability repaired by different techniques.
Staphylococcus aureus
Isolates with Reduced Susceptibility to Glycopeptides Belong to Accessory Gene Regulator Group I or II
Authors: Verdier Isabelle , Reverdy Marie-Elisabeth , Etienne Jerome , Lina Gérard , Bes Michèle , Vandenesch François 
Published: February 2004

ABSTRACT

We used multiplex PCR to determine the
agr
group membership of 18 European glycopeptide heterointermediate and intermediate-resistant
Staphylococcus aureus
strains. Of the 15
agr
group I strains, 13 were resistant and 2 were susceptible to methicillin. The remaining three strains, like the United States and Japanese control strains, belonged to
agr
group II.
Role of
attP
in Integrase-Mediated Integration of the
Shigella
Resistance Locus Pathogenicity Island of
Shigella flexneri
Authors: Turner Sally A. , Luck Shelley N. , Sakellaris Harry , Rajakumar Kumar , Adler Ben 
Published: February 2004

ABSTRACT

The
Shigella
resistance locus (SRL) pathogenicity island (PAI) in
Shigella
spp. mediates resistance to streptomycin, ampicillin, chloramphenicol, and tetracycline. It can be excised from the chromosome via site-specific recombination mediated by the P4-related
int
gene. Here, we show that SRL PAI
attP
is capable of RecA-independent, site-specific,
int
-mediated integration into two bacterial tRNA
attB
sites.
Comparative Efficacies of Four Amphotericin B Formulations—Fungizone, Amphotec (Amphocil), AmBisome, and Abelcet—against Systemic Murine Aspergillosis
Authors: Clemons Karl V. , Stevens David A. 
Published: February 2004

ABSTRACTWe compared various amphotericin B formulations (no treatment or 0.8 mg of Fungizone [conventional deoxycholate amphotericin B] per kg of body weight, or 0.8, 4, or 8 mg of Amphocil, AmBisome, or Abelcet per kg of body weight) for treatment of systemic murine aspergillosis. In two studies, all formulations prolonged survival, with the results for AmBisome nearly equivalent to those for Fungizone; Amphocil and Abelcet were less effective or equivalent depending on the severity of infection. No survivors were cured in both kidneys and brain, but each formulation showed efficacy, especially in the kidneys. Although higher doses could be given, no lipid-based formulation showed consistent superiority over Fungizone or over each other.
Antibiotic Susceptibility of
Tropheryma whipplei
in MRC5 Cells
Authors: Boulos Areen , Rolain Jean-Marc , Raoult Didier 
Published: February 2004

ABSTRACT

Whipple's disease is considered a rare chronic disease with a broad spectrum of clinical manifestations. Several antibiotics have been used for the treatment of this disease, and the current reference treatment was determined empirically on the basis of only a few clinical observations. Patients should be treated for months, and many relapse after antibiotic withdrawal. We report here the first extensive study on the susceptibilities of three reference strains of
Tropheryma whipplei
to antibiotic in cell culture by using a real-time PCR assay as previously described. We found that doxycycline, macrolides, ketolides, aminoglygosides, penicillin, rifampin, teicoplanin, chloramphenicol, and trimethoprim-sulfamethoxazole were active, with MICs ranging from 0.25 to 2 μg/ml. Vancomycin was somewhat active at an MIC of 10 μg/ml. We found heterogeneity in the susceptibility to imipenem, with one strain being susceptible and the two other strains being resistant. Cephalosporins, colimycine, aztreonam, and fluoroquinolones were not active. We also demonstrated that a combination of doxycycline and hydroxychloroquine was bactericidal. This combination has been shown to be active in the treatment of patients suffering from chronic infections with
Coxiella burnetii
, a bacterium that is also found intracellularly in acidic vacuoles. We believe, then, that this combination therapy should be further evaluated in clinical trials for the treatment of Whipple's disease.
Pharmacokinetics of Indinavir and Nelfinavir in Treatment-Naive, Human Immunodeficiency Virus-Infected Subjects
Authors: DiCenzo Robert , Forrest Alan , Fischl Margaret A. , Collier Ann , Feinberg Judith , Ribaudo Heather , DiFrancecso Robin , Morse Gene D. 
Published: February 2004

ABSTRACT

AIDS Clinical Trials Group protocol 388 was designed to compare a three-drug regimen (indinavir with dual nucleosides) to a four-drug regimen (indinavir plus nelfinavir or indinavir plus efavirenz with dual nucleosides). Blood samples from patients taking indinavir and nelfinavir were collected over 8 to 12 h following a specified dose and were analyzed with high-performance liquid chromatography. Pharmacokinetic data were derived by using noncompartmental analysis. Following administration of indinavir every 8 h in the absence of nelfinavir (
n
= 8), the median predose indinavir concentration (
C
0
) was 369 ng/ml (range, <10 to 949 ng/ml; one subject had a concentration of <10 ng/ml), and the concentration 8 h after administration of the study dose was 159 ng/ml (range, 85 to 506 ng/ml). In the group receiving 1,000 mg of indinavir every 12 h with nelfinavir (
n
= 10), the median indinavir
C
0
was <10 ng/ml (range, <10 to 3,740 ng/ml; six subjects had a value of <10 ng/ml), and the
C
12 h
was 44 ng/ml (range, <10 to 4,236 ng/ml; five subjects had a value of <10 ng/ml), while the subjects who received 1,200 mg of indinavir every 12 h with nelfinavir (
n
= 7) had a
C
0
of 146 ng/ml (range, 58 to 5,215 ng/ml) and a
C
12 h
of 95 ng/ml (range, 12 to 954 ng/ml). Indinavir clearance was significantly lower in the presence of nelfinavir (median [interquartile range], 34.1 liters/h [range, 22.6 to 45.8 liters/h] versus 47.9 liters/h [range, 42.7 to 70.3 liters/h];
P
< 0.017). For subjects receiving 1,000 mg of indinavir every 12 h, the median
C
0
value for nelfinavir (
n
= 9) was 1,779 ng/ml (range, <187.5 to 4,579 ng/ml), and the
C
12 h
was 1,554 ng/ml (range, <187.5 to 5,540 ng/ml). Due to the unacceptable number of undetectable indinavir trough concentrations, 1,200 mg of indinavir appears to be the preferred dose in a twice-daily regimen that includes nelfinavir.
Plasmodium falciparum-Based Bioassay for Measurement of Artemisinin Derivatives in Plasma or Serum
Authors: Teja-Isavadharm Paktiya , Peggins James O. , Brewer Thomas G. , White Nicholas J. , Webster H. Kyle , Kyle Dennis E. 
Published: February 2004

ABSTRACTArtemisinin and its derivatives, artesunate and artemether, are rapidly acting antimalarials that are used for the treatment of severe and uncomplicated multidrug-resistant falciparum malaria. To optimize treatment regimens that use this new class of antimalarials, there is a need for readily available and reproducible assays to monitor drug levels closely in patients. A sensitive and reproducible bioassay for the measurement of the concentrations of artemisinin derivatives in plasma and serum is described. By modifying the in vitro drug susceptibility test, it was found that antimalarial activity in plasma or serum containing an unknown concentration of drug could be equated to the known concentrations of dihydroartemisinin (DHA) required to inhibit parasite growth. Dose-response curves for aPlasmodium falciparumclone (clone W2) and DHA were used as a standard for each assay. Assays with plasma or serum spiked with DHA proved to be reproducible (coefficient of variation, ≤10.9%), with a lower limit of quantitation equivalent to 2.5 ng of DHA per ml. For plasma spiked with artesunate or artemether, there was good agreement of the results obtained by the bioassay and the concentrations measured by high-performance liquid chromatography (HPLC) with electrochemical detection. The bioassay for measurement of the antimalarial activities of artemisinin derivatives in body fluids requires a smaller volume of plasma or serum and is more sensitive than the presently available HPLC methods, can provide pharmacodynamic parameters for determination of activity against the parasite, and should enhance the design of more appropriate dosage regimens for artemisinin drugs.
Intrapatient Variability of Efavirenz Concentrations as a Predictor of Virologic Response to Antiretroviral Therapy
Authors: Brundage Richard C. , Yong Florence H. , Fenton Terence , Spector Stephen A. , Starr Stuart E. , Fletcher Courtney V. 
Published: February 2004

ABSTRACTIntrapatient variability of drug concentrations over time has not been evaluated as a predictor of drug response but may provide information on the onset and maintenance of response and a patient's adherence to therapy. Our objective was to develop a pharmacologically based measure of intrapatient variability of concentrations and investigate its association with a patient's response to antiretroviral therapy. Efavirenz concentrations were obtained for 50 children enrolled in Pediatric AIDS Clinical Trials Group study 382, a concentration-controlled trial of efavirenz plus nelfinavir and at least one nucleoside reverse transcriptase inhibitor. Efavirenz pharmacokinetic parameters were determined from 24-h concentration-time profiles at weeks 2 and 6 and used to predict trough concentrations obtained during 1 year of therapy. A concentration predictability score, defined as the fraction of measured trough concentrations that fell within a ±50% range of the predicted concentration, was used to place subjects into high and low concentration predictability groups. Relationships between this score and human immunodeficiency virus RNA levels in plasma were investigated. Eight of 33 children (24%) in the high-predictability group experienced viral rebound, compared with 9 of 17 children (53%) in the low-predictability group (P= 0.042). Children with low predictability scores exhibited a significantly shorter time to their first viral rebounds and were significantly more likely to experience viral rebound; the latter finding persisted after adjustment for baseline viral load and efavirenz exposure at week 6. This novel method for the quantitation of intrapatient concentration variability was independently predictive of virologic rebound. This measure may allow interventions to minimize therapeutic failure and is applicable to other drugs.
Molecular Mechanisms of Tenofovir Resistance Conferred by Human Immunodeficiency Virus Type 1 Reverse Transcriptase Containing a Diserine Insertion after Residue 69 and Multiple Thymidine Analog-Associated Mutations
Authors: White Kirsten L. , Chen James M. , Margot Nicolas A. , Wrin Terri , Petropoulos Christos J. , Naeger Lisa K. , Swaminathan S. , Miller Michael D. 
Published: February 2004

ABSTRACTTwo amino acids inserted between residues 69 and 70 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) are rare mutations that may develop in viruses containing multiple thymidine analog (zidovudine [AZT], stavudine)-associated mutations and that confer high-level resistance to all currently approved chain-terminating nucleoside and nucleotide RT inhibitors (NRTIs). The two known mechanisms of resistance to NRTIs are decreased incorporation and increased excision. The mechanism used by RT insertion mutants has not been described for tenofovir (TFV), a recently approved agent in this class. A patient-derived HIV-1 strain (strain FS-SSS) that contained an insertion mutation in a background of additional resistance mutations M41L, L74V, L210W, and T215Y was obtained. A second virus (strain FS) was derived from FS-SSS. In strain FS the insertion and T69S were reverted but the other resistance mutations were retained. The FS virus showed strong resistance to AZT but low-level changes in susceptibilities to other NRTIs and TFV. The FS-SSS virus showed reduced susceptibilities to all NRTIs including TFV. Steady-state kinetics demonstrated that the relative binding or incorporation of TFV was slightly decreased for FS-SSS RT compared to those for wild-type RT. However, significant ATP-mediated excision of TFV was detected for both mutant RT enzymes and followed the order FS-SSS RT > FS RT > wild-type RT. The presence of physiological concentrations of the +1 nucleotide inhibited TFV excision by the wild-type RT and slightly inhibited excision by the FS RT, whereas the level of excision by the FS-SSS RT remained high. Computer modeling suggests that the increased mobility of the β3-β4 loop may contribute to the high-level and broad NRTI resistance caused by the T69 insertion mutation.
High prevalence of autoreactive, neuroantigen-specific CD8+ T cells in multiple sclerosis revealed by novel flow cytometric assay
Authors: Crawford Michael P. , Yan Shirley X. , Ortega Sterling B. , Mehta Riyaz S. , Hewitt Rachel E. , Price David A. , Stastny Peter , Douek Daniel C. , Koup Richard A. , Racke Michael K. , Karandikar Nitin J. 
Published: February 2004

AbstractMultiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS) with features suggestive of T-cell-mediated pathology. Most prior reports have focused on CD4+ T cells with the underlying assumption that MS is predominantly a CD4+ T helper 1 (Th1)-mediated disease. In this report, we used a novel flow cytometric approach to evaluate autoreactive T-cell responses against a large variety of neuroantigenic targets. We found that both CD4+ and CD8+ T cells targeted against several CNS autoantigens were widely prevalent in patients with MS and healthy individuals. Whereas the distribution of CD4+ responses was similar in different groups, patients with relapsing-remitting MS showed a higher proportion of CNS-specific CD8+ responses. Autoreactive CD4+ T cells from patients with MS exhibited a more differentiated Th1 phenotype compared with healthy subjects. Similarly, CNS-specific CD8+ T-cell responses from patients with MS were functionally distinct from those in healthy individuals. Collectively, these studies reveal the high prevalence of class I-restricted autoreactive CD8+ T-cell responses in MS that has been underappreciated thus far. The results emphasize the need to evaluate both CD4+ and CD8+ T-cell responses in MS and to make both subsets a consideration in the development of novel therapeutic strategies. (Blood. 2004; 103:4222-4231)
Acute Monocytic Leukemia (French-American-British classification M5) Does Not Have a Worse Prognosis Than Other Subtypes of Acute Myeloid Leukemia: A Report From the Eastern Cooperative Oncology Group
Authors: Tallman Martin S. , Kim Haesook T. , Paietta Elisabeth , Bennett John M. , Dewald Gordon , Cassileth Peter A. , Wiernik Peter H. , Rowe Jacob M. 
Published: February 2004

Purpose Acute monocytic leukemia is a distinct subtype of acute myeloid leukemia (AML) with characteristic biologic and clinical features. This study was designed to compare the outcome of patients with M5 to that of other subtypes of AML, and to identify differences in M5a and M5b. Patients and Methods We reviewed all patients with AML M5 entered in three clinical trials for newly diagnosed AML conducted by the Eastern Cooperative Oncology Group between 1989 and 1998. Eighty-one patients, 21 with M5a and 60 with M5b, were identified. Results The complete remission rate was 62% for all patients with M5; 52% for patients with M5a and 65% for patients with M5b (P = .3), and 60% for the 1,122 patients with non-M5 AML entered on the same clinical trials (P = .8 for M5 v non-M5). The 3-year disease-free survival was 26% for all M5 patients; 18% for M5a and 28% for M5b (P = .31), and 33% for non-M5 patients (P = .13 for M5 v non-M5). The 3-year overall survival was 31% for all M5 patients; 33% for M5a and 30% for M5b (P = .65), and 30% for non-M5 (P = .74 for M5 v non-M5). The karyotypes of patients with AML M5 were heterogeneous. CD11b was the only leukemic cell antigen expressed differently in M5a (53%) compared to M5b (77%) to a significant degree (P = .02). Conclusion AML M5 represents an immunologically heterogeneous population similar to non-M5 AML with a prognosis that is not dependent on morphology. The disease-free survival and overall survival of patients with M5a, M5b, and non-M5 appear not to differ with currently available therapy.
Chiral Bis(12-crown-4)-based Electrodes for Sodium Ion
Authors: Shibutani Yasuhiko , Mino Shigeto , Long Shen Shuang , Moriuchi-Kawakami Takayo , Yakabe Kenji , Shono Toshiyuki 
Published: March 2004

Abstract
New optically active bis(12-crown-4) based electrodes for Na+ were evaluated. The best selectivity (log k = −2.3) was obtained when the sensors were used in association with NPOE as a plasticizing solvent mediator and NaHFPB as an anion excluder in PVC matrices. Na+ selectivity against K+ was augmented by a factor of nearly two using R,R- or S,S- bis(12-crown-4) compared with that of optically inactive bis(12-crown-4)s reported previously.
Investigating the limits of filopodial sensing: a brief report using SEM to image the interaction between 10 nm high nano‐topography and fibroblast filopodia
Authors: Dalby M.J. , Riehle M.O. , Johnstone H. , Affrossman S. , Curtis A.S.G 
Published: February 2004

AbstractHaving the ability to control cell behaviour would be of great advantage in tissue engineering. One method of gaining control over cell adhesion, proliferation, guidance and differentiation is use of topography. Whilst it has be known for some time that cells can be guided by micro‐topography, it is only recently becoming clear that cells will respond strongly to nano‐scale topography. The fact that cells will take cues from their micro‐ and nano‐environment suggests that the cells are in some way ‘spatially aware’. It is likely that cells probe the shape of their surroundings using filopodia, and that this initial filopodia/topography interaction may be critical to down‐stream cell reactions to biomaterials, or indeed, the extracellular matrix. One intriguing question is how small a feature can cells sense? In order to investigate the limits of cell sensing, high‐resolution scanning electron microscopy has been used to simultaneously view cell filopodia and 10 nm high nano‐islands. Fluorescence microscopy has also been used to look at adhesion formation. The results showed distinct filopodial/nano‐island interaction and changes in adhesion morphology.
Apoptosis and nitric oxide release induced by thalidomide, gossypol and dexamethasone in cultured human chronic myelogenous leukemic K‐562 cells
Authors: Ergun Mehmet Ali , Konac Ece , Erbas Deniz , Ekmekci Abdullah 
Published: February 2004

AbstractThe effects of different dosages of thalidomide, gossypol and dexamethasone on the levels of apoptosis and nitric oxide (NO) production were studied in a human chronic myelogenous leukemic cell line, K‐562. Increases in the levels of apoptosis were induced by both 15 and 30 μM of thalidomide but only 15 μM significantly increased NO production. All dosages of gossypol used increased the production of NO and all dosages except 200 μM raised the level of apoptosis. After dexamethasone treatment the level of NO either decreased or stayed constant. Thus, some dosages of thalidomide and gossypol concomitantly raise the levels of apoptosis and NO production, but dexamethasone, though it induced apoptosis, had no significant effect on NO production.
In situ target strength of the Baltic Sea herring and sprat
Authors: Didrikas Tomas , Hansson Sture 
Published: February 2004

Abstract
Using single- and split-beam hydroacoustic equipment (70 and 38 kHz), and gillnet and trawl catches, we derived the relationship TS = 25.5 log10 L − 73.6 (r2=0.95) between acoustic target strength (TS) and fish length (L, cm) for Baltic Sea herring (Clupea harengus membras L.) and sprat (Sprattus sprattus balticus (Schneider)). Fixing the slope to 20, which is a standard practice in hydroacoustics, gave TS = 20 log10 L − 67.8 (r2=0.91). Normally, the fisheries agencies around the Baltic use a TS–length relationship that is based mainly on data from the North Sea and the intercept-value in this equation is 3.4 dB lower than that reported in this paper. This difference corresponds to an approximately twofold difference in assessed stock biomass.
Bone mass is preserved in a critical‐sized osteotomy by low energy pulsed electromagnetic fields as quantitated by in vivo micro‐computed tomography
Authors: Ibiwoye Michael O. , Powell Kimerly A. , Grabiner Mark D. , Patterson Thomas E. , Sakai Yoshitada , Zborowski Maciej , Wolfman Alan , Midura Ronald J. 
Published: February 2004

AbstractThe effectiveness of non‐invasive pulsed electromagnetic fields (PEMF) on stimulating bone formation in vivo to augment fracture healing is still controversial, largely because of technical ambiguities in data interpretation within several previous studies. To address this uncertainty, we implemented a rigorously controlled, blinded protocol using a bilateral, mid‐diaphyseal fibular osteotomy model in aged rats that achieved a non‐union status within 3–4 weeks post‐surgery. Bilateral osteotomies allowed delivery of a PEMF treatment protocol on one hind limb, with the contralateral limb representing a within‐animal sham‐treatment. Bone volumes in both PEMF‐treated and sham‐treated fibulae were assessed simultaneously in vivo using highly sensitive, high‐resolution micro‐computed tomography (μCT) over the course of treatment. We found a significant reduction in the amount of time‐dependent bone volume loss in PEMF‐treated, distal fibular segments as compared to their contralateral sham‐treated bones. Osteotomy gap size was significantly smaller in hind limbs exposed to PEMF over sham‐treatment. Therefore, our data demonstrate measurable biological consequences of PEMF exposure on in vivo bone tissue. © 2004 Orthopaedic Research Society. Published y Elsevier Ltd. All rights reserved.