bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics-Pharmacodynamics of Rifampin in an Aerosol Infection Model of Tuberculosis
Authors: Jayaram Ramesh , Gaonkar Sheshagiri , Kaur Parvinder , Suresh B. L. , Mahesh B. N. , Jayashree R. , Nandi Vrinda , Bharat Sowmya , Shandil R. K. , Kantharaj E. , Balasubramanian V. 
Published: June 2003

ABSTRACT

Limited information exists on the pharmacokinetic (PK)-pharmacodynamic (PD) relationships of drugs against
Mycobacterium tuberculosis
. Our aim was to identify the PK-PD parameter that best describes the efficacy of rifampin on the basis of in vitro and PK properties. Consistent with 83.8% protein binding by equilibrium dialysis, the rifampin MIC for
M. tuberculosis
strain H37Rv rose from 0.1 in a serum-free system to 1.0 mg/ml when it was tested in the presence of 50% serum. In time-kill studies, rifampin exhibited area under the concentration-time curve (AUC)-dependent killing in vitro, with maximal killing seen on all days and with the potency increasing steadily over a 9-day exposure period. MIC and time-kill studies performed with intracellular organisms in a macrophage monolayer model yielded similar results. By use of a murine aerosol infection model with dose ranging and dose fractionation over 6 days, the PD parameter that best correlated with a reduction in bacterial counts was found to be AUC/MIC (
r
2
= 0.95), whereas the maximum concentration in serum/MIC (
r
2
= 0.86) and the time that the concentration remained above the MIC (
r
2
= 0.44) showed lesser degrees of correlation.
High-Level Expression of AmpC β-Lactamase Due to Insertion of Nucleotides between −10 and −35 Promoter Sequences in
Escherichia coli
Clinical Isolates: Cases Not Responsive to Extended-Spectrum-Cephalosporin Treatment
Authors: Siu L. K. , Lu Po-Liang , Chen J.-Y. , Lin F. M. , Chang Shan-Chwen 
Published: June 2003

ABSTRACT

Two
Escherichia coli
isolates were recovered from the blood of two cancer patients and were demonstrated to produce high levels of the AmpC β-lactamase with isoelectric points of >9.0. The hypertranscription of
ampC
RNA was observed by Northern blot hybridization in both isolates. One isolate (isolate EC44) had a point mutation (G→A at position −28) and insertion of thymidine between positions −20 and −19 of the
ampC
promoter gene (GenBank accession no.
AE000487
). The single nucleotide insertion of T between positions −19 and −20 created an optimal distance (17 bp) in the Pribnow box for
ampC
hyperproduction. The other isolate (isolate EC38) had two point mutations (G→A at position −28 and C→T at position +58) and a 2-base (GT) insertion between positions −14 and −15. Although the insertion of GT between positions −14 and −15 may create a new promoter next to the original promoter, cloning of the
ampC
region with truncated nucleotides of the original −35 region of EC38 failed to verify the hypothesis that a new promoter would be created by such a nucleotide insertion. Instead, multiple start sites for
ampC
transcription at −1, +1, +2, and +3 were observed in an S1 nuclease protection assay. These results suggest that the RNA polymerase is flexible in the selection of a start site in
ampC
hypertranscription. In conclusion, nucleotide insertions between the −35 and −10
ampC
promoter sequences was the mechanism for the hyperproduction of AmpC β-lactamase and resistance to oxyimino-cephalosporins. The failure of the two patients to respond to treatment with oxyimino-cephalosporins highlights the important role of such a resistance mechanism in the clinical setting.
Randomized Open Trial of Gentamicin and Doxycycline for Eradication of
Bartonella quintana
from Blood in Patients with Chronic Bacteremia
Authors: Foucault C. , Raoult D. , Brouqui P. 
Published: June 2003

ABSTRACT

Chronic
Bartonella quintana
bacteremia is known to occur in homeless people exposed to lice. We present here the results of an open randomized trial performed to evaluate the efficacy of doxycycline in combination with gentamicin in the eradication of
B. quintana
bacteremia. From 1 January 2001 to 1 April 2002, homeless people with blood cultures positive for
B. quintana
were randomized to receive either no treatment (untreated controls) or a combination of gentamicin (3 mg/kg of body weight/day intravenously for 14 days) and doxycycline (200 mg/day orally for 28 days). Patients were evaluated from the results of blood cultures performed between day 28 (the end of treatment) and day 90 postinclusion. Intention-to-treat analysis of 20 included patients showed eradication of bacteremia in 7 out of 9 treated patients versus 2 out of 11 untreated controls (
P
= 0.01). In the per-protocol analysis, eradication was obtained for 7 out of 7 treated patients versus 2 out of 9 untreated controls (
P
= 0.003). This study demonstrates the efficiency of the combination of doxycycline and gentamicin in eradicating
B. quintana
bacteremia.
Plasmid-Mediated Quinolone Resistance in Clinical Isolates of
Escherichia coli
from Shanghai, China
Authors: Wang Minggui , Tran John H. , Jacoby George A. , Zhang Yingyuan , Wang Fu , Hooper David C. 
Published: June 2003

ABSTRACT

Although quinolone resistance usually results from chromosomal mutations, recent studies indicate that quinolone resistance can also be plasmid mediated. The gene responsible,
qnr
, is distinct from the known quinolone resistance genes and in previous studies seemed to be restricted to
Klebsiella pneumoniae
and
Escherichia coli
isolates from the University of Alabama in Birmingham, where this resistance was discovered. In Shanghai, the frequency of ciprofloxacin resistance in
E. coli
has exceeded 50% since 1993. Seventy-eight unique ciprofloxacin-resistant clinical isolates of
E. coli
from Shanghai hospitals were screened for the
qnr
gene by colony blotting and Southern hybridization of plasmid DNA. Conjugation experiments were done with azide-resistant
E. coli
J53 as a recipient with selection for plasmid-encoded antimicrobial resistance (chloramphenicol, gentamicin, or tetracycline) and azide counterselection.
qnr
genes were sequenced, and the structure of the plasmid DNA adjacent to
qnr
was analyzed by primer walking with a sequential series of outward-facing sequencing primers with plasmid DNA templates purified from transconjugants. Six (7.7%) of 78 strains gave a reproducible hybridization signal with a
qnr
gene probe on colony blots and yielded strong signals on plasmid DNA preparations. Quinolone resistance was transferred from all six probe-positive strains. Transconjugants had 16- to 250-fold increases in the MICs of ciprofloxacin relative to that of the recipient. All six strains contained
qnr
with a nucleotide sequence identical to that originally reported, except for a single nucleotide change (CT
A
→CT
G
at position 537) encoding the same amino acid.
qnr
was located in complex In4 family class 1 integrons. Two completely sequenced integrons were designated In36 and In37. Transferable plasmid-mediated quinolone resistance associated with
qnr
is thus prevalent in quinolone-resistant clinical strains of
E. coli
from Shanghai and may contribute to the rapid increase in bacterial resistance to quinolones in China.
Recombinant Single-Chain Variable Fragment Antibodies Directed againstClostridium difficileToxin B Produced by Use of an Optimized Phage Display System
Authors: Deng Xiao K. , Nesbit Lance A. , Morrow K. John 
Published: July 2003

ABSTRACTRecombinant antibody cloning and phage display technologies were used to produce single-chain antibodies (scFv) againstClostridium difficiletoxin B. The starting material was the mouse B cell hybridoma line 5A8, which generates a monoclonal antibody against the toxin. The integrated cloning, screening, and phage display system of Krebber et al. (J. Immunol. Methods201:35-55, 1997) allowed us to rapidly obtain toxin B-binding scFv sequences derived from the hybridoma cell line. The best candidate scFv sequences, based on preliminary enzyme-linked immunosorbent assay (ELISA) screening data were then subcloned into the compatible expression vector. Recombinant single-chain antibodies were expressed inEscherichia coli.A 29-kDa band was observed on polyacrylamide gel electrophoresis as predicted. The expressed product was characterized by immunoblotting and detection with an anti-FLAG antibody. The toxin B-binding function of the single-chain antibody was shown by a sandwich ELISA. The antibody was highly specific for toxin B and did not cross-react with material isolated from a toxin B-negativeC. difficilestrain. The sensitivity of the soluble single-chain antibody is significantly higher than the original monoclonal antibody based on ELISA data and could detect a minimum of 10 ng of toxin B/well. Competitive ELISAs established that the affinity of the 5A8 parent antibody and the best representative (clone 10) of the single-chain antibodies were similar and in the range of 10−8M. We propose that recombinant antibody technology is a rapid and effective approach to the development of the next generation of immunodiagnostic reagents.
Differences in Clinical Manifestations and Hematological and Serological Responses after Experimental Infection with Genetic Variants ofAnaplasma phagocytophilumin Sheep
Authors: Stuen Snorre , Bergström Karin , Petrovec Miroslav , Van de Pol Ingrid , Schouls Leo M. 
Published: July 2003

ABSTRACTFive-month-old lambs were experimentally infected with two 16S rRNA genetic variants ofAnaplasma phagocytophilum, variants 1 (GenBank accession no.M73220) and 2 (GenBank accession no.AF336220). Additional sequencing of thegroESLheat shock operon gene indicated that these variants differ in three nucleotides at positions 782, 824, and 890. The variants were obtained by blood sampling ofA.phagocytophilum-infected lambs from one sheep flock in Norway and were stored at −70°C with 10% dimethyl sulfoxide as a cryoprotectant before being inoculated intravenously into susceptible lambs. The infectious blood contained, per ml, approximately 0.5 × 106neutrophils infected with either of the variants. Six weeks after the primary inoculation, the lambs were challenged with the same infectious dose of the heterologous variant. The results of the study indicate a marked difference in clinical manifestation, neutropenia, antibody response, and cross-protection after experimental infection with the two variants ofA. phagocytophilum.
The Theory of Reflexive Modernization
Authors: Beck Ulrich , Bonss Wolfgang , Lau Christoph 
Published: July 2003

How can one distinguish the concept of second modernity from the concept of postmodernity? Postmodernists are interested in deconstruction without reconstruction, second modernity is about deconstruction and reconstruction. Social sciences need to construct new concepts to understand the world dynamics at the beginning of the 21st century.Modernity has not vanished, we are not post it. Radical social change has always been part of modernity. What is new is that modernity has begun to modernize its own foundations. This is what it means to say modernity has become reflexive. It has become directed at itself. This causes huge new problems both in reality and in theory. There has been a pluralization of the boundaries within and between societies, between society and nature, between Us and Other, between life and death. This pluralization also changes the inherent nature of boundaries. They become not so much boundaries as a variety of attempts to draw of boundaries. Border conflicts become transformed into conflicts over the drawing of boundaries. Where postmodernism simply celebrates this multiplication of boundaries, the theory of second modernity starts with the problem this new reality poses for individual and collective decisions, and with the problem that the continued existence of such decisions poses for theory. Institutions that are capable of such conscious boundary drawing are enabled in a way that those of the first modernity were not. But this process also generates qualitatively new kinds of trouble and crises. To investigate those troubles is to unveil the emergence of the second modernity.
Airflow Optimizing Control Research Based on Genetic Algorithm During Mine Fire Period
Authors: Zhong Maohua , Xing Wei , Weicheng Fan , Peide Li , Baozhi Chen 
Published: July 2003

Mine fire is a very complex physicochemical process. Once it happens, there are lots of poisonous and harmful gas ingredients while the oxygen density is greatly reduced. Such gas will cause poison, suffocation or death if it is inhaled. As we know, the main cause of great amount of person losses during mine fire is fume poison and suffocation. Additionally, the fume caused by the fire will block the vision and decrease the visibility, which will impede human evacuation and fire fighting. Moreover, due to the turbulent airflow of ventilation network during mine fire period, it is easy to cause the gas and coal dust explosion. So it is very important for the evacuation of miners and mining salvation to research the air flow control during mine fire. In this paper, Genetic Algorithm (GA) is used to solve wind-flow quantitative optimizing control. And in “Introduction” we introduce some researches of airflow control of mining fire. In “Main Principles of Airflow Control During Mine Fire Period”, the fundamental principles of airflow control during mine fire are introduced. The airflow optimizing control models are introduced in “Nonlinear Programming Model of Air Current Optimum Control During Mine Fire Period”. In “Computation of Nonlinear Programming of Airflow Control During Mining Fire Period”, the computation methods and the selection of relative parameters of the control model are discussed. Finally, a computation example is given.
Rasburicase for the Treatment and Prevention of Hyperuricemia
Authors: Yim Barbara T , Sims-McCallum Rosalyn P , Chong Pang H 
Published: June 2003

OBJECTIVE: To review the information currently available on rasburicase for treatment and prevention of hyperuricemia. DATA SOURCES: MEDLINE (1966–August 2002) was searched for primary and review articles. STUDY SELECTION/DATA EXTRACTION: Studies evaluating rasburicase, including abstracts and proceedings, were considered for inclusion. English-language literature was evaluated for the pharmacology, pharmacodynamics, pharmacokinetics, therapeutic use, and adverse effects of rasburicase. DATA SYNTHESIS: Rasburicase, a recombinant urate oxidase, has been shown to be effective in lowering uric acid and preventing uric acid accumulation in patients with hematologic malignancies who had hyperuricemia or who were at high risk for developing hyperuricemia. It has been approved for pediatric use in the US. CONCLUSIONS: In addition to allopurinol, hydration, and urinary alkalinization, rasburicase is a new alternative for the treatment and prevention of hyperuricemia in patients with hematologic malignancies. Its rapid onset of action and the ability to lower preexisting elevated uric acid levels are the advantages of rasburicase compared with allopurinol. It may allow the patient to receive chemotherapy treatment without delay.
Acamprosate for the Adjunctive Treatment of Alcohol Dependence
Authors: Overman Gerald P , Teter Christian J , Guthrie Sally K 
Published: June 2003

OBJECTIVE: To review the literature related to the treatment of alcohol dependence with acamprosate, a synthetic compound structurally similar to the naturally occurring amino acid, homotaurine. DATA SOURCES: Primary literature and review articles were identified by MEDLINE search (1966–June 2003). Abstracts from recent meetings were also reviewed. DATA SYNTHESIS: Acamprosate has been marketed in 24 countries. Although the precise mechanism of acamprosate in the treatment of alcohol-dependent patients is unclear, it may restore the balance between inhibitory and excitatory neurotransmission in the central nervous system. European trials have shown consistent increases in abstinence rates compared with placebo when acamprosate use was paired with appropriate psychosocial and behavioral therapies. Decreased direct and indirect healthcare costs associated with acamprosate treatment have also been reported. CONCLUSIONS: Acamprosate is a promising medication for the treatment of alcohol dependence in the US.
A Simplified Analytical Procedure for the Determination of Organically Bound Halogens in Salt‐containing Water Samples
Authors: Borsdorf Helko , Fiedler Petra , Wilke Dorit , Weiß Holger 
Published: July 2003

AbstractA method was developed for the determination of organic halogens in water samples with the aim of minimizing matrix effects and simplifying the sample preparation technique commonly used. The method is based on the adsorption of organic halogens in modified hydrophilic divinylbenzene polymer columns and their elution with methanol. The adsorbent used enables rapid adsorption and desorption due to comparatively high operating flow rates and minimized solvent amounts. Furthermore, no additional reconcentration steps are needed. The methanol extract obtained is combusted with a standard EOX (extractable organic halogen) analyzer and the concentration of organically bound halogens is determined by microcoulometric analysis. The matrix effects are considerably reduced compared to the standard procedure (EN 1485) commonly used. A detection limit of 13 μg/L was established.
Myristyl Dimethylamine Oxide Surfactant Solutions: Model Systems for Rheological Research
Authors: Pflaumbaum Manuela , Rehage Heinz 
Published: July 2003

AbstractAqueous surfactant solutions of entangled, rod‐shaped micelles are often characterized by monoexponential stress‐relaxation processes. This special phenomenon leads to relatively simple theoretical descriptions, and viscoelastic surfactant solutions can, therefore, also be used as simple model systems for studying fundamental principles of flow. Herein, we present a detailed study of the nonlinear rheological properties of aqueous myristyl dimethylamine oxide surfactant solutions. In the regime of small deformations, shear stresses, or shear rates, the dynamic features of the viscoelastic solutions are characterized by the simple equations of a Maxwell material. At elevated values of shear stresses or deformations, however, this simple model fails and nonlinear features, such as normal stresses, stress overshoots, or shear‐thinning properties occur. All these phenomena can be described by a Maxwell‐type differential constitutive equation, which was first proposed by Giesekus. It turns out that the experimental results are in fairly good agreement with the theoretical predictions, if the anisotropy factor α is equal to 0.5. Besides transient data and nonlinear steady‐state measurements, many semiempirical laws, such as the Cox–Merz rule, the Yamamoto relation, the Laun equation, and the Gleißle mirror relationships are approximately satisfied. The dynamic properties discussed in this paper are of general importance and they are equally observed in different materials such as polymer, dye, or protein solutions.
A Half‐Century with Solar Neutrinos (Nobel Lecture)
Authors: Davis, Jr. Raymond 
Published: July 2003

AbstractThe Sun derives its energy from fusion reactions in which hydrogen is transformed into helium. Every time four protons are turned into a helium nucleus, two neutrinos are produced. These neutrinos take only two seconds to reach the surface of the Sun and another eight minutes or so to reach the Earth. Thus, neutrinos tell us what happened in the center of the Sun eight minutes ago. The Sun produces one‐third as many neutrinos as predicted by the standard solar model of particle physics. The author's pioneering work proved that nothing was wrong with the experiments or the theory; something was “wrong” with the neutrinos, in the sense that they behave in ways beyond the standard model.
Derivatization of inorganic ions in capillary electrophoresis
Authors: Padarauskas Audrius 
Published: July 2003

AbstractThis review gives a short overview of the main approaches to the derivatization of inorganic ions in capillary electrophoresis (CE) with emphasis on the most recent works. Various derivatization procedures and detection methods are discussed. A brief account of their advantages and limitations is given. More specific areas such as microchip CE, simultaneous separation of anions and cations, and speciation analysis are also briefly discussed.
Interest and limitations of projective techniques in the assessment of personality disorders
Authors: Petot J.M. 
Published: July 2003

SummaryAssessing personality disorders (PD) remains a difficult task because of persistent problems linked to concurrent validity of existing instruments, which are all structured interviews or self-report inventories. It has been advocated that indirect methods, projective techniques in particular, can strengthen PD assessment methods. The thematic apperception test (TAT) may be a significant adjuvant method of PD assessment.
Antibiotic prescribing for children. Too much and too little? Retrospective observational study in primary care
Authors: Ekins‐Daukes Suzie , McLay James S. , Taylor Michael W. , Simpson Colin R. , Helms Peter J. 
Published: July 2003

Aims  To investigate the extent of dose‐related off‐label antibiotic paediatric prescribing in primary care and to identify any potential clinical effects, particularly of lower than recommended dose prescribing.Methods  Assessment of antibiotic prescribing in 168 396 children aged 0–16 years for the year 1999–2000 from data retrieved from 158 general practices using the national Scottish primary care computer system GPASS. The setting was general practices in Scotland.Results  During the study period at least one course of antibiotics was prescribed to 23 911 children (14.2%). A total of 4582 (19.2%) children were prescribed an antibiotic dose of less than that recommended in the Summary of Product Characteristics (SPC). The number of children prescribed an antibiotic at less than recommended dose increased with age from 1154 (11.8%) aged 0–4 years to 1827 (30.0%) in the 12–16 years age group. For each antibiotic, prescribing lower than recommended dose occurred most frequently at those ages at which a dose increase was recommended in the SPC. Antibiotic prescribing at less than the recommended dose was not associated with an increased return rate for further antibiotic prescriptions during the following month, but in 5–11‐year‐olds was associated with a significant 48% increase in the total number of antibiotic courses prescribed during the study year {mean = 2.09 [95% confidence interval (CI) 1.79, 2.39]vs. 1.41 [95% CI 1.35, 1.47]}. Antibiotic prescribing at doses higher than recommended occurred less frequently (1.6%) and decreased steadily with age.Conclusions  Off‐label prescribing of antibiotics at less than the recommended dose in children is common in primary care and occurs primarily as the result of a failure to increase antibiotic dosage with age in line with SPC recommendations. Adoption of a uniform approach to SPC age banding for antibiotic dose increments would reduce the frequency of dose‐related off‐label antibiotic prescribing in children and help minimize the potential for the development of antibiotic resistance.