bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics and Safety of Intravenous Voriconazole in Children after Single- or Multiple-Dose Administration
Authors: Walsh Thomas J. , Karlsson Mats O. , Driscoll Timothy , Arguedas Adriano G. , Adamson Peter , Saez-Llorens Xavier , Vora Ajay J. , Arrieta Antonio C. , Blumer Jeffrey , Lutsar Irja , Milligan Peter , Wood Nolan 
Published: May 2004

ABSTRACT
We conducted a multicenter study of the safety, tolerability, and plasma pharmacokinetics of the parenteral formulation of voriconazole in immunocompromised pediatric patients (2 to 11 years old). Single doses of 3 or 4 mg/kg of body weight were administered to six and five children, respectively. In the multiple-dose study, 28 patients received loading doses of 6 mg/kg every 12 h on day 1, followed by 3 mg/kg every 12 h on day 2 to day 4 and 4 mg/kg every 12 h on day 4 to day 8. Standard population pharmacokinetic approaches and generalized additive modeling were used to construct the structural pharmacokinetic and covariate models used in this analysis. In contrast to that in adult healthy volunteers, elimination of voriconazole was linear in children following doses of 3 and 4 mg/kg every 12 h. Body weight was more influential than age in accounting for the observed variability in voriconazole pharmacokinetics. Elimination capacity correlated with the CYP2C19 genotype. Exposures were similar at 4 mg/kg every 12 h in children (median area under the concentration-time curve (AUC), 14,227 ng · h/ml) and 3 mg/kg in adults (median AUC, 13,855 ng · h/ml). Visual disturbances occurred in 5 (12.8%) of the 39 patients and were the only drug-related adverse events that occurred more than once. No withdrawals from the study were related to voriconazole. We conclude that pediatric patients have a higher capacity for elimination of voriconazole per kilogram of body weight than do adult healthy volunteers and that dosages of 4 mg/kg may be required in children to achieve exposures consistent with those in adults following dosages of 3 mg/kg.
Short- and Long-Term Effects of Pneumococcal Conjugate Vaccination of Children on Penicillin Resistance
Authors: Temime L. , Guillemot D. , Boëlle P. Y. 
Published: May 2004

ABSTRACT

Recent observations have shown that wide-scale vaccination with pneumococcal conjugate vaccines was associated with a reduction in invasive disease, supporting the expectation that vaccination could help reduce carriage of
Streptococcus pneumoniae
and control the spread of resistant strains. However, it is too early to assess whether these effects can be sustained in the long term. Here, we used mathematical modeling to investigate time changes in pneumococcal colonization and resistance induced by conjugate vaccination in an environment where antibiotic exposure is high and resistance is widespread. According to model predictions, vaccination induced a decrease in carriage of vaccine-type pneumococci to very low levels, typically in 10 to 15 years under epidemiologically realistic conditions. Almost simultaneously, non-vaccine-type pneumococci spread in the community. Consequently, while there was a short-term decrease in the overall carriage rate, it was followed after a few years by a renewed, although limited, increase. Vaccination with a heptavalent vaccine did not affect the extent to which antibiotic resistance was selected: in all cases, the distribution of resistance levels peaked at high levels (MIC > 2 μg/ml) after 20 years. With a vaccine optimally designed to include all serotypes currently exhibiting decreased susceptibility to penicillin G, the selection of resistance was slowed down, although not prevented. These results suggest that because of serotype replacement, the effects of vaccination observed today may not be sustained in the long term. As a consequence, vaccination alone may not be successful in controlling selection for resistance in
S. pneumoniae
.
Sulfadoxine Resistance in
Plasmodium vivax
Is Associated with a Specific Amino Acid in Dihydropteroate Synthase at the Putative Sulfadoxine-Binding Site
Authors: Korsinczky Michael , Fischer Katja , Chen Nanhua , Baker Joanne , Rieckmann Karl , Cheng Qin 
Published: May 2004

ABSTRACT

Sulfadoxine is predominantly used in combination with pyrimethamine, commonly known as Fansidar, for the treatment of
Plasmodium falciparum
. This combination is usually less effective against
Plasmodium vivax
, probably due to the innate refractoriness of parasites to the sulfadoxine component. To investigate this mechanism of resistance by
P. vivax
to sulfadoxine, we cloned and sequenced the
P. vivax dhps
(
pvdhps
) gene. The protein sequence was determined, and three-dimensional homology models of dihydropteroate synthase (DHPS) from
P. vivax
as well as
P. falciparum
were created. The docking of sulfadoxine to the two DHPS models allowed us to compare contact residues in the putative sulfadoxine-binding site in both species. The predicted sulfadoxine-binding sites between the species differ by one residue, V585 in
P. vivax
, equivalent to A613 in
P. falciparum
. V585 in
P. vivax
is predicted by energy minimization to cause a reduction in binding of sulfadoxine to DHPS in
P. vivax
compared to
P. falciparum
. Sequencing
dhps
genes from a limited set of geographically different
P. vivax
isolates revealed that V585 was present in all of the samples, suggesting that V585 may be responsible for innate resistance of
P. vivax
to sulfadoxine. Additionally, amino acid mutations were observed in some
P. vivax
isolates in positions known to cause resistance in
P. falciparum
, suggesting that, as in
P. falciparum
, these mutations are responsible for acquired increases in resistance of
P. vivax
to sulfadoxine.
Mechanism of Action at the Molecular Level of the Antiviral Drug 3(2H)-Isoflavene against Type 2 Poliovirus
Authors: Salvati Anna L. , De Dominicis Alessandra , Tait Sabrina , Canitano Andrea , Lahm Armin , Fiore Lucia 
Published: May 2004

ABSTRACT
The mechanism of action of the antiviral compound 3(2H)-isoflavene against Sabin type 2 poliovirus has been studied, and interference with virus uncoating was demonstrated. Isolation and sequencing of drug-resistant variants revealed single amino acid substitutions (I194M or D131V) in the VP1 capsid protein. While M194 is located in a hydrophobic pocket and should partially fill the space occupied by the isoflavene ring, V131 is exposed on the VP1 surface, forming a contact with VP4. The D131V mutation most likely induces local conformational changes in VP1 and/or VP4 that affect viral flexibility. Two dependent variants, N53S of VP1 and K58E of VP4, both located on the inner surface of the capsid, near the threefold axis of symmetry, were also selected. Both mutations affected viral stability, allowing the transition to 135S particles in the absence of drug, without the involvement of the viral receptor.
Complete Sequences of Six Penicillin-Binding Protein Genes from 40
Streptococcus pneumoniae
Clinical Isolates Collected in Japan
Authors: Sanbongi Yumiko , Ida Takashi , Ishikawa Midori , Osaki Yumi , Kataoka Hiroshi , Suzuki Takahisa , Kondo Kumiko , Ohsawa Fukuichi , Yonezawa Minoru 
Published: May 2004

ABSTRACT

All six penicillin-binding protein (PBP) genes, namely,
pbp1a
,
pbp1b
,
pbp2a
,
pbp2b
,
pbp2x
, and
pbp3
, of 40
Streptococcus pneumoniae
clinical isolates, including penicillin-resistant
S. pneumoniae
isolates collected in Japan, were completely sequenced. The MICs of penicillin for these strains varied between 0.015 and 8 μg/ml. In PBP 2X, the Thr550Ala mutation close to the KSG motif was observed in only 1 of 40 strains, whereas the Met339Phe mutation in the STMK motif was observed in six strains. These six strains were highly resistant (MICs ≧ 2 μg/ml) to cefotaxime. The MICs of cefotaxime for 27 strains bearing the Thr338Ala mutation tended to increase, but the His394Leu mutation next to the SSN motif did not exist in these strains. In PBP 2B, the Thr451Ala/Phe/Ser and Glu481Gly mutations close to the SSN motif were observed in 24 strains, which showed penicillin resistance and intermediate resistance, and the Thr624Gly mutation close to the KTG motif was observed in 2 strains for which the imipenem MIC (0.5 μg/ml) was the highest imipenem MIC detected. In PBP 1A, the Thr371Ser/Ala mutation in the STMK motif was observed in all 13 strains for which the penicillin MICs were ≧1 μg/ml. In PBP 2A, the Thr411Ala mutation in the STIK motif was observed in one strain for which with the cefotaxime MIC (8 μg/ml) was the highest cefotaxime MIC detected. On the other hand, in PBPs 1B and 3, no mutations associated with resistance were observed. The results obtained here support the concept that alterations in PBPs 2B, 2X, and 1A are mainly involved in
S. pneumoniae
resistance to β-lactam antibiotics. Our findings also suggest that the Thr411Ala mutation in PBP 2A may be associated with β-lactam resistance.
Enhanced Production of Farnesol by
Candida albicans
Treated with Four Azoles
Authors: Hornby Jacob M. , Nickerson Kenneth W. 
Published: May 2004

ABSTRACT

The dimorphic fungus
Candida albicans
excretes farnesol, which is produced enzymatically from the sterol biosynthetic intermediate farnesyl pyrophosphate. Inhibition of
C. albicans
by four azole antifungals, fluconazole, ketoconazole, miconazole, and clotrimazole, caused elevated farnesol production (10- to 45-fold). Furthermore, farnesol production occurs in both laboratory strains and clinical isolates (J. M. Hornby et al., Appl. Environ. Microbiol. 67:2982-2992, 2001) of
C. albicans
.
Immunopharmacology of CpG Oligodeoxynucleotides and Ribavirin
Authors: Vollmer Jörg , Rankin Robert , Hartmann Hanna , Jurk Marion , Samulowitz Ulrike , Wader Tanja , Janosch Andrea , Schetter Christian , Krieg Arthur M. 
Published: May 2004

ABSTRACT
To investigate their potential mechanisms of action, the nucleoside analogue ribavirin and a TLR9 agonist were compared. The CpG oligodeoxynucleotides (ODN) demonstrated strong TLR9-related Th1-type effects, and ribavirin appeared only to mediate signaling in TLR-transfected cells. CpG ODN represent a promising new type of therapeutic drug for hepatitis C or other infectious diseases.
Effect of massage of the hamstring muscle group on performance of the sit and reach test
Authors: Barlow A , Clarke R , Johnson N , Seabourne B , Thomas D , Gal J 
Published: May 2004

Objective:To investigate if a single massage of the hamstring muscle group would alter the performance of the sit and reach test.Methods:Before treatment, each of 11 male subjects performed the sit and reach test. The treatment consisted of either massage of the hamstring muscle group (both legs, total time about 15 minutes) or supine rest with no massage. Performance of the sit and reach test was repeated after treatment. Each subject returned the subsequent week to perform the tests again, receiving the alternative treatment relative to their initial visit. Mean percentage changes in sit and reach scores after treatment were calculated for the massage and no massage treatments, and analysed using Student’sttests.Results:Mean (SD) percentage changes in sit and reach scores after massage and no massage were small (6.0 (4.3)% and 4.6 (4.8)% respectively) and not significantly different for subjects with relatively high (15 cm and above) values before treatment. Mean percentage changes in sit and reach scores for subjects with relatively low values before treatment (below 15 cm) were large (18.2 (8.2)% and 15.5 (16.2)% respectively), but no significant differences were found between the massage and no massage groups.Conclusions:A single massage of the hamstring muscle group was not associated with any significant increase in sit and reach performance immediately after treatment in physically active young men.
Do physical leisure time activities prevent fatigue? A 15 month prospective study of nurses’ aides
Authors: Eriksen W , Bruusgaard D 
Published: May 2004

Objective:To test the hypothesis that physical leisure time activities reduce the risk of developing persistent fatigue.Methods:The hypothesis was tested in a sample that was homogeneous with respect to sex and occupation, with a prospective cohort design. Of 6234 vocationally active, female, Norwegian nurses’ aides, not on leave because of illness or pregnancy when they completed a mailed questionnaire in 1999, 5341 (85.7%) completed a second questionnaire 15 months later. The main outcome measure was the prevalence of persistent fatigue—that is, always or usually feeling fatigued in the daytime during the preceding 14 days.Results:In participants without persistent fatigue at baseline, reported engagement in physical leisure time activities for 20 minutes or more at least once a week during the three months before baseline was associated with a reduced risk of persistent fatigue at the follow up (odds ratio  =  0.70; 95% confidence interval 0.55 to 0.89), after adjustments for age, affective symptoms, sleeping problems, musculoskeletal pain, long term health problems of any kind, smoking, marital status, tasks of a caring nature during leisure time, and work factors at baseline.Conclusion:The study supports the hypothesis that physical leisure time activities reduce the risk of developing persistent fatigue.
Effects of androgenic-anabolic steroids on apolipoproteins and lipoprotein (a)
Authors: Hartgens F , Rietjens G , Keizer H A , Kuipers H , Wolffenbuttel B H R 
Published: May 2004

Objectives:To investigate the effects of two different regimens of androgenic-anabolic steroid (AAS) administration on serum lipid and lipoproteins, and recovery of these variables after drug cessation, as indicators of the risk for cardiovascular disease in healthy male strength athletes.Methods:In a non-blinded study (study 1) serum lipoproteins and lipids were assessed in 19 subjects who self administered AASs for eight or 14 weeks, and in 16 non-using volunteers. In a randomised double blind, placebo controlled design, the effects of intramuscular administration of nandrolone decanoate (200 mg/week) for eight weeks on the same variables in 16 bodybuilders were studied (study 2). Fasting serum concentrations of total cholesterol, triglycerides, HDL-cholesterol (HDL-C), HDL2-cholesterol (HDL2-C), HDL3-cholesterol (HDL3-C), apolipoprotein A1 (Apo-A1), apolipoprotein B (Apo-B), and lipoprotein (a) (Lp(a)) were determined.Results:In study 1 AAS administration led to decreases in serum concentrations of HDL-C (from 1.08 (0.30) to 0.43 (0.22) mmol/l), HDL2-C (from 0.21 (0.18) to 0.05 (0.03) mmol/l), HDL3-C (from 0.87 (0.24) to 0.40 (0.20) mmol/l, and Apo-A1 (from 1.41 (0.27) to 0.71 (0.34) g/l), whereas Apo-B increased from 0.96 (0.13) to 1.32 (0.28) g/l. Serum Lp(a) declined from 189 (315) to 32 (63) U/l. Total cholesterol and triglycerides did not change significantly. Alterations after eight and 14 weeks of AAS administration were comparable. No changes occurred in the controls. Six weeks after AAS cessation, serum HDL-C, HDL2-C, Apo-A1, Apo-B, and Lp(a) had still not returned to baseline concentrations. Administration of AAS for 14 weeks was associated with slower recovery to pretreatment concentrations than administration for eight weeks. In study 2, nandrolone decanoate did not influence serum triglycerides, total cholesterol, HDL-C, HDL2-C, HDL3-C, Apo-A1, and Apo-B concentrations after four and eight weeks of intervention, nor six weeks after withdrawal. However, Lp(a) concentrations decreased significantly from 103 (68) to 65 (44) U/l in the nandrolone decanoate group, and in the placebo group a smaller reduction from 245 (245) to 201 (194) U/l was observed. Six weeks after the intervention period, Lp(a) concentrations had returned to baseline values in both groups.Conclusions:Self administration of several AASs simultaneously for eight or 14 weeks produces comparable profound unfavourable effects on lipids and lipoproteins, leading to an increased atherogenic lipid profile, despite a beneficial effect on Lp(a) concentration. The changes persist after AAS withdrawal, and normalisation depends on the duration of the drug abuse. Eight weeks of administration of nandrolone decanoate does not affect lipid and lipoprotein concentrations, although it may selectively reduce Lp(a) concentrations. The effect of this on atherogenesis remains to be established.
Etomidate for Procedural Sedation in the Emergency Department
Authors: Keim Samuel M. , Erstad Brian L. , Sakles John C. , Davis Virgil 
Published: May 2004

Study Objective. To review our experience with etomidate in nonintubated patients in the emergency department.Design. A 2‐year retrospective chart review of consecutive patients receiving etomidate for sedation.Setting. Emergency department of a university‐based teaching hospital.Patients. Forty‐eight patients who underwent painful procedures in the emergency department.Measurements and Main Results. Demographics, dosing information, recovery times, and adverse events were abstracted using a standardized data collection form. Forty‐eight nonintubated patients were sedated with etomidate. Mean age was 34 years (range 6–80 yrs); 38 were men and 10 women; two were children. The mean initial dose of etomidate was 13 mg. Adverse events occurred in 11 (21%) patients. None sustained any substantial morbidity as indicated by need for intubation, prolonged emergency department stay, or hospital admission.Conclusion. Although controversial, etomidate holds promise as a potent sedative agent for patients undergoing painful procedures in the emergency department. A large prospective evaluation is needed to document the performance and complications of this agent.
Percutaneous revascularization of the common femoral artery for limb ischemia
Authors: Silva Jose A. , White Christopher J. , Quintana Hugo , Collins Tyrone J. , Jenkins J. Stephen , Ramee Stephen R. 
Published: May 2004

AbstractWe performed percutaneous transluminal intervention in 20 consecutive patients (21 limbs) with common femoral artery (CFA) lesions causing symptomatic limb ischemia. In 12 limbs, concurrent additional percutaneous intervention proximal or distal to the target CFA lesion was performed. Angiographic success was obtained in 100%, with procedural success (angiographic success without a major in‐hospital complications) in 90% and clinical success (procedural success and in‐hospital improvement by at least one Fontaine functional class) in 81% of the limbs. The in‐hospital Fontaine class improved by at least one functional class in 17 of 19 patients (89%), and the overall in‐hospital event‐free survival was 90% (18 of 20 patients). At follow‐up (11.4 ± 6 months), the overall event‐free survival was 90% (18 of 20 patients) and 17 of 19 patients (89%) continue to show improvement by at least one functional (Fontaine) class. Percutaneous intervention of the CFA can be performed with a rate of high technical success and a low complication rate. It provides excellent clinical results at mid‐term follow‐up and appears to be a reasonable alternative to surgical therapy in patients at high risk for surgery. Catheter Cardiovasc Interv 2004;62:230–233. © 2004 Wiley‐Liss, Inc.
Use of IIb/IIIa inhibitors in patients with in‐stent restenosis treated with intracoronary γ‐radiation: Integrilin WRIST
Authors: Waksman Ron , Ajani Andrew E. , Gruberg Luis , Pinnow Ellen , GebreEyesus Afework , Deible Regina , Satler Lowell F. , Pichard Augusto D. , Torguson Rebecca , Kent Kenneth M. , Suddath William , Lindsay Joseph 
Published: May 2004

AbstractThe Integrilin Washington Radiation for In‐Stent Restenosis Trial (WRIST) aimed to study the impact of IIb/IIIa inhibitors as adjunct therapy to intracoronary radiation therapy (IRT) for patients with in‐stent restenosis (ISR). The impact of GP IIb/IIIa inhibitor (eptifibatide) as adjunct therapy to vascular brachytherapy using 192Ir emitter was examined in patients with in‐stent restenosis. In the study, 150 patients were assigned to eptifibatide (Integrilin) and 150 patients to heparin only. Clinical composite endpoints at 30 days were similar between the patients treated with and without eptifibatide (4.7% vs. 4.0%; P = 0.78). There was a similarity in the non‐Q‐wave myocardial infarction (MI) rates between the eptifibatide and the control group. Major bleeding was similar in patients treated with and without eptifibatide. Overall, the use of eptifibatide as adjunct therapy for patients with ISR that are treated with IRT did not impact the clinical outcome at 30 days. Catheter Cardiovasc Interv 2004;62:162–166. © 2004 Wiley‐Liss, Inc.
Contribution to the stability analysis of the dewetted Bridgman growth under microgravity conditions
Authors: Bizet L. , Duffar T. 
Published: May 2004

AbstractExperimental observations show that the gap between the sample and the crucible, commonly obtained after solidification in microgravity, is remarkably stable. With the aim to understand the reason of this stability, the dewetting phenomenon is studied by Lyapunov's method. After a short review of the existing mechanisms leading to dewetting, the open smooth crucible configuration is chosen as the most representative. The analytical stability analysis, taking into account geometrical and thermal effects, performed under some boundary heat transfer approximations, shows that, in most cases, the dewetting process is intrinsically stable. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
On the effects of Ga3+ and La3+ ions in MgCu ferrite: Humidity‐sensitive electrical conduction
Authors: Rezlescu N. , Rezlescu E. , Sava C.‐L. , Tudorache F. , Popa P. D. 
Published: May 2004

AbstractPure and gallium or lanthanum substituted MgCu ferrites, Mg0.5Cu0.5Fe2‐xMxO4 (with x = 0 or 0.2 and M = La or Ga) have been prepared by solid state reaction. Sintering experiments were carried out at different temperatures between 900 and 1100°C. The phase composition and lattice parameters were determined by XRD, while the effect of Ga and La substitutions on the granular structure was studied by SEM. Experimental results revealed that the densification behaviour and some physical properties are in close relation with the structural changes of pure ferrite caused by the presence of La and Ga substitutions. The gallium containing compound, Mg0.5Cu0.5Fe1.8Ga0.2O4, is monophasic and contains a great number of pores, whereas the lanthanum containing compound, Mg0.5Cu0.5Fe1.8La0.2O4, is biphasic and exhibits a high density. The humidity characteristics show that the gallium ion enhances the humidity sensitivity of the MgCu ferrite sintered at 1000°C. This interesting effect is promising for the future of the Ga‐substituted MgCu ferrite to be used as sensitive material for fabrication of ceramic humidity sensors. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)