bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nurse Practitioners' and Physicians' Care Activities and Clinical Outcomes With an Inpatient Geriatric Population
Authors: Lambing Angela Y. , Adams Denise L. C. , Fox Dorothy H. , Divine George 
Published: May 2005

ObjectiveLess is known about nurse practitioners' (NPs') effectiveness in acute care than about their effectiveness in outpatient settings. This study investigated care activities and clinical outcomes for hospitalized geriatric patients treated by NPs compared with those treated by intern and resident physicians.Data SourcesA descriptive comparative research design involved random selection of 100 inpatient geriatric patients and a convenience sample of 17 professional providers who staffed three hospital units. A 1‐month study period produced retrospective and prospective data for analysis.Self‐reports concerning 10 primary activity categories indicated that NPs spent a higher percentage of time doing progress notes and care planning than did physicians (28% versus 15%, p=.011) and that physicians spent more time on literature reviews (5% versus 1%, p=.008). When prioritizing care activities, NPs ranked advance directive discussion higher than did physicians (2nd versus 7th, p=.036), a difference confirmed by medical record documentation. Physicians were more attentive to functional status (1st versus 3rd, p=.023), but medical record documentation showed NPs to be more attentive to physical and occupational therapy referrals (p=.001). Analysis of 13 independent organ areas revealed that NPs cared for more musculoskeletal (p=.036) and psychiatric (p=.005) problems. Physicians cared for more cardiac patients (p=.001). NPs’ patients were older (p=.022) and sicker at admission (p <. 001) and discharge (p <. 001). Charges per length of stay were lower (p <. 001) for the physician provider group, and patients in that group had shorter stays (p <. 001). Readmission and mortality rates were similar.Implications for PracticeNPs provide effective care to hospitalized geriatric patients, particularly to those who are older and sicker.
Clinical Evaluation and Patterns of Chemotherapy‐Induced Peripheral Neuropathy
Authors: Visovsky Constance , Daly Barbara J. 
Published: May 2005

PurposeTo determine the pattern of change in peripheral nerve function (as measured by vision, hearing, deep tendon reflexes, vibratory sense, cutaneous sensation, gait and balance, muscle strength, and orthostatic blood pressure) occurring among individuals receiving cancer treatment with known neurotoxic agents.Data SourcesA convenience sample of 16 participants with cancer who were receiving chemotherapy had their peripheral nerve function assessed at baseline and at 4 weeks and 12 weeks of treatment. Data were analyzed using plots and regression slopes to determine change over time in clinical measures of peripheral nerve function. Outcome variables were vision, hearing, deep tendon reflexes, vibratory sense, cutaneous sensation, gait and balance, muscle strength, and changes in orthostatic blood pressure.ConclusionsThis is the first prospective study to use comprehensive clinical measures of peripheral nerve and muscle changes resulting from combination chemotherapy or a biotherapy regimen. Alterations in vision, hearing, deep tendon reflexes, vibratory sense, cutaneous sensation, balance, muscle strength, and orthostatic blood pressure were noted, but gait remained unchanged.Implications for PracticeThis study provides beginning evidence of the need for careful, ongoing assessment of treatment‐induced peripheral neuropathy. Standardized clinical practice procedures that incorporate patient evaluation for peripheral neuropathy must still be developed.In addition, we must educate our patients about the functional changes they may expect, and we must develop strategies to assist them in managing limitations that they experience as a result of peripheral neuropathy.
Attitudes of Registered Nurses Toward Nurse Practitioners
Authors: Gooden Janet M. , Jackson Elaine 
Published: May 2005

PurposeRegistered nurses (RNs)work closely with nurse practitioners (NPs) in all facets of patient care and often have a direct influence on the patient's perception of the professional who is directing the care, and a patient's perceptions may affect clinical outcomes. However, few studies have been conducted to measure RN acceptance of the NP. The authors surveyed RNs in southern Illinois to assess their attitudes concerning the level of care provided by NPs. Southern Illinois was chosen because of the limited number of NPs in the area and because of concerns that limited exposure might negatively influence RN attitudes about the NP role.Data CollectionA 26‐item research questionnaire, previously used with school nurses, was modified to reflect RNs in general. Seven items related to demographic information, and 19 items created a five‐response Likert‐formatted scale (r=.93). The questionnaire was mailed to 500 randomly selected RNs from the 11 southernmost counties of Illinois.ConclusionsThe results showed support of the NP role. RNs believed that NPs were knowledgeable, competent health care providers. RNs were also comfortable working with NPs and often consulted them for advice and information. They saw the role of the NP as a positive addition to the health care team.Implications for PracticeOne identified concern was that scores indicated RNs felt that they received limited respect from NPs. Although the scores were high in this category, some RNs had concerns that NPs might not respect or understand the difficulty of the RN role in providing patient care. NPs need to recognize their collegial and professional ties to RNs and should take time to provide positive feedback to RNs as they collaborate to provide health care. Such behavior would only solidify the health team approach.
IMP Dehydrogenase from the Protozoan ParasiteToxoplasma gondii
Authors: Sullivan William J. , Dixon Stacy E. , Li Catherine , Striepen Boris , Queener Sherry F. 
Published: May 2005

ABSTRACTThe opportunistic apicomplexan parasiteToxoplasma gondiidamages fetuses in utero and threatens immunocompromised individuals. The toxicity associated with standard antitoxoplasmal therapies, which target the folate pathway, underscores the importance of examining alternative pharmacological strategies. Parasitic protozoa cannot synthesize purines de novo; consequently, targeting purine salvage enzymes is a plausible pharmacological strategy. Several enzymes critical to purine metabolism have been studied inT. gondii, but IMP dehydrogenase (IMPDH), which catalyzes the conversion of IMP to XMP, has yet to be characterized. Thus, we have cloned the gene encoding this enzyme inT. gondii. Northern blot analysis shows that two IMPDH transcripts are present inT. gondiitachyzoites. The larger transcript contains an open reading frame of 1,656 nucleotides whose deduced protein sequence consists of 551 amino acids (TgIMPDH). The shorter transcript is an alternative splice product that generates a 371-amino-acid protein lacking the active-site flap (TgIMPDH-S). When TgIMPDH is expressed as a recombinant protein fused to a FLAG tag, the fusion protein localizes to the parasite cytoplasm. Immunoprecipitation with anti-FLAG was employed to purify recombinant TgIMPDH, which converts IMP to XMP as expected. Mycophenolic acid is an uncompetitive inhibitor relative to NAD+, with a intercept inhibition constant (Kii) of 0.03 ± 0.004 μM. Tiazofurin and its seleno analog were not inhibitory to the purified enzyme, but adenine dinucleotide analogs such as TAD and the nonhydrolyzable β-methylene derivatives of TAD or SAD were inhibitory, withKiivalues 13- to 60-fold higher than that of mycophenolic acid.
Pharmacodynamic Modeling of the Evolution of Levofloxacin Resistance in
Staphylococcus aureus
Authors: Campion Jeffrey J. , Chung Philip , McNamara Patrick J. , Titlow William B. , Evans Martin E. 
Published: May 2005

ABSTRACT

Previously, we demonstrated the importance of low-level-resistant variants to the evolution of resistance in
Staphylococcus aureus
exposed to ciprofloxacin in an in vitro system and developed a pharmacodynamic model which predicted the emergence of resistance. Here, we examine and model the evolution of resistance to levofloxacin in
S. aureus
exposed to simulated levofloxacin pharmacokinetic profiles. Enrichment of subpopulations with mutations in
grlA
and low-level resistance varied with levofloxacin exposure. A regimen producing average steady-state concentrations (
C
avg ss
) just above the MIC selected
grlA
mutants with up to 16-fold increases in the MIC and often additional mutations in
grlA/grlB
and
gyrA
. A regimen providing
C
avg ss
between the MIC and the mutant prevention concentration (MPC) suppressed bacterial numbers to the limit of detection and prevented the appearance of bacteria with additional mutations or high-level resistance. Regimens producing
C
avg ss
above the MPC appeared to eradicate low-level-resistant variants in the cultures and prevent the emergence of resistance. There was no relationship between the time concentrations remained between the MIC and the MPC and the degree of resistance or the presence or type of mutations that appeared in
grlA/B
or
gyrA
. Our pharmacodynamic model described the growth and levofloxacin killing of the parent strains and the most resistant
grlA
mutants in the starting cultures and correctly predicted conditions that enrich subpopulations with low-level resistance. These findings suggest that the pharmacodynamic model has general applicability for describing fluoroquinolone resistance in
S. aureus
and further demonstrate the importance of low-level-resistant variants to the evolution of resistance.
Detection of
rpoB
Mutations Associated with Rifampin Resistance in
Mycobacterium tuberculosis
Using Denaturing Gradient Gel Electrophoresis
Authors: McCammon Mark T. , Gillette John S. , Thomas Derek P. , Ramaswamy Srinivas V. , Graviss Edward A. , Kreiswirth Barry N. , Vijg Jan , Quitugua Teresa N. 
Published: May 2005

ABSTRACT

Denaturing gradient gel electrophoresis (DGGE) was used to probe for mutations associated with rifampin (RIF) resistance in the
rpoB
gene of
Mycobacterium tuberculosis
. DGGE scans for mutations across large regions of DNA and is comparable to DNA sequencing in detecting DNA alterations. Specific mutations are often recognized by their characteristic denaturation pattern, which serves as a molecular fingerprint. Five DGGE primer sets that scanned for DNA alterations across 775 bp of
rpoB
were developed. These primer sets were used to scan
rpoB
for DNA alterations in 296
M. tuberculosis
patient isolates from the United States-Mexico border states of Texas and Tamaulipas. The most useful primer set scanned for mutations in the rifampin resistance-determining region (RRDR) and detected mutations in 95% of the RIF-resistant isolates compared to 2% of RIF-susceptible isolates. Thirty-four different alterations were observed within the RRDR by DGGE. In addition, isolates harboring mixtures of DNA within
rpoB
were readily detected by DGGE. A second PCR primer set was used to detect the V146A mutation in 5 to 7% of RIF-resistant isolates. A third primer set was used to detect mutations in 3% of RIF-resistant isolates, some of which also harbored mutations in the RRDR. Only 1 of 153 RIF-resistant isolates did not have a detectable
rpoB
mutation as determined by DGGE and DNA sequencing. These results demonstrate the power and usefulness of DGGE in detecting mutations associated with drug resistance in
M. tuberculosis
.
Detection by Denaturing Gradient Gel Electrophoresis of
pncA
Mutations Associated with Pyrazinamide Resistance in
Mycobacterium tuberculosis
Isolates from the United States-Mexico Border Region
Authors: McCammon Mark T. , Gillette John S. , Thomas Derek P. , Ramaswamy Srinivas V. , Rosas Ishmael I. , Graviss Edward A. , Vijg Jan , Quitugua Teresa N. 
Published: May 2005

ABSTRACT

Denaturing gradient gel electrophoresis (DGGE) was used to probe for mutations associated with pyrazinamide (PZA) resistance in the
pncA
gene of
Mycobacterium tuberculosis
. DGGE scans for mutations across large regions of DNA and rivals sequencing in its ability to detect DNA alterations. Specific mutations can often be recognized by their characteristic denaturation pattern, which serves as a molecular fingerprint. Five PCR target fragments were designed to scan for DNA alterations across 600 bp of
pncA
in 181
M. tuberculosis
isolates from patients residing in the U.S-Mexico border states of Texas and Tamaulipas, respectively. A region of
pncA
was observed with a high GC content and a melting temperature approaching 90°C that was initially refractory to denaturation, and a DGGE target fragment was specifically designed to detect mutations in this region. DGGE detected
pncA
mutations in 82 of 83 PZA-resistant isolates. By contrast, only 1 of 98 PZA-susceptible isolates harbored a detectable DNA alteration. The
pncA
gene was sequenced from 41 isolates, and 32 DNA alterations in 32 PZA-resistant isolates were identified, including 11 new mutations. DGGE also detected nine isolates whose susceptibility to PZA appeared to be incorrect, and DNA sequencing confirmed these apparent errors in drug susceptibility testing. These results demonstrate the power and usefulness of DGGE in detecting mutations associated with PZA resistance in
M. tuberculosis
.
In Vitro Antiviral Activity and Single-Dose Pharmacokinetics in Humans of a Novel, Orally Bioavailable Inhibitor of Human Rhinovirus 3C Protease
Authors: Patick Amy K. , Brothers Mary A. , Maldonado Fausto , Binford Susan , Maldonado Oscar , Fuhrman Shella , Petersen Annkatrin , Smith George J. , Zalman Leora S. , Burns-Naas Leigh Ann , Tran Jonathan Q. 
Published: May 2005

ABSTRACT

(E)-(S)-4-((S)-2-{3-[(5-methyl-isoxazole-3-carbonyl)-amino]-2-oxo-2H-pyridin-1-yl}-pent-4-ynoylamino)-5-((S)-2-oxo-pyrrolidin-3-yl)-pent-2-enoic acid ethyl ester (Compound 1) is a novel, irreversible inhibitor of human rhinovirus (HRV) 3C protease {inactivation rate constant (K
obs
/[I]) of 223,000 M
−1
s
−1
}. In cell-based assays, Compound 1 was active against all HRV serotypes (35 of 35), HRV clinical isolates (5 of 5), and related picornaviruses (8 of 8) tested with mean 50% effective concentration (EC
5
0
) values of 50 nM (range, 14 to 122 nM), 77 nM (range, 72 to 89 nM), and 75 nM (range, 7 to 249 nM), respectively. Compound 1 inhibited HRV 3C-mediated polyprotein processing in infected cells in a concentration-dependent manner, providing direct confirmation that the cell-based antiviral activity is due to inhibition of 3C protease. In vitro and in vivo nonclinical safety studies showed Compound 1 to be without adverse effects at maximum achievable doses. Single oral doses of Compound 1 up to 2,000 mg in healthy volunteers were found to be safe and well tolerated in a phase I-ascending, single-dose study. Compound 1 estimated free observed maximum concentration in plasma (
C
ma
x
) for 500-, 1,000-, and 2,000-mg doses were higher than the protein binding-corrected EC
50
required to inhibit 80% of the HRV serotypes tested. Treatment of HRV 52-infected cells with one to five 2-h pulses of 150 nM Compound 1 (corresponding to the
C
max
at the 500-mg dose) was sufficient to effect a significant reduction in viral replication. These experiments highlight Compound 1 as a potent, orally bioavailable, irreversible inhibitor of HRV 3C protease and provide data that suggest that
C
max
rather than the
C
min
might be the key variable predicting clinical efficacy.
Occurrence of HypermutablePseudomonas aeruginosain Cystic Fibrosis Patients Is Associated with the Oxidative Stress Caused by Chronic Lung Inflammation
Authors: Ciofu Oana , Riis Bente , Pressler Tacjana , Poulsen Henrik Enghusen , Høiby Niels 
Published: May 2005

ABSTRACTOxidative stress caused by chronic lung inflammation in patients with cystic fibrosis (CF) and chronic lung infection withPseudomonas aeruginosais characterized by the reactive oxygen species (ROS) liberated by polymorphonuclear leukocytes (PMNs). We formulated the hypothesis that oxidation of the bacterial DNA by ROS presents an increased risk for the occurrence of hypermutableP. aeruginosa. The occurrence of hypermutableP. aeruginosaisolates was investigated directly in the sputum of 79 CF patients and among 141 isolates collected from 11 CF patients (10 to 15 isolates/patient) collected from the 1st and up to the 25th year of their chronic lung infection. The level of oxidized guanine moiety 8-oxo-2′-deoxyguanosine (8-oxodG), which is a frequently investigated DNA oxidative lesion, was measured. HypermutableP. aeruginosaisolates were found in the sputum bacterial population of 54.4% of the CF patients. The earliest mutatorP. aeruginosaisolates were found after 5 years from the onset of the chronic lung infection, and once they were present in the CF lung, the prevalence increased with time. The hypermutable isolates were significantly more resistant to antipseudomonal antibiotics than nonhypermutable isolates (P≤ 0.001). The level of 8-oxodG/106deoxyguanosine (dG) was significantly higher in hypermutableP. aeruginosaisolates (87 ± 38) than in nonhypermutableP. aeruginosaisolates (59.4 ± 17) (P= 0.02), and an increase to 86.84 from 21.65 8-oxodG/106dG was found after exposure of the reference strain PAO1 to activated PMNs. Our results suggest that the chronic PMN inflammation in the CF lung promotes oxidative stress and is associated with the occurrence of hypermutable bacteria in the lung. The hypermutable phenotype can associate with mutations that confer adaptation of the bacteria in the lung and persistence of the infection.
Preclinical Testing of the Nitroimidazopyran PA-824 for Activity against
Mycobacterium tuberculosis
in a Series of In Vitro and In Vivo Models
Authors: Lenaerts Anne J. , Gruppo Veronica , Marietta Karen S. , Johnson Christine M. , Driscoll Diane K. , Tompkins Nicholas M. , Rose Jerry D. , Reynolds Robert C. , Orme Ian M. 
Published: May 2005

ABSTRACT

This study extends earlier reports regarding the in vitro and in vivo efficacies of the nitroimidazopyran PA-824 against
Mycobacterium tuberculosis
. PA-824 was tested in vitro against a broad panel of multidrug-resistant clinical isolates and was found to be highly active against all isolates (MIC < 1 μg/ml). The activity of PA-824 against
M. tuberculosis
was also assessed grown under conditions of oxygen depletion. PA-824 showed significant activity at 2, 10, and 50 μg/ml, similar to that of metronidazole, in a dose-dependent manner. In a short-course mouse infection model, the efficacy of PA-824 at 50, 100, and 300 mg/kg of body weight formulated in methylcellulose or cyclodextrin/lecithin after nine oral treatments was compared with those of isoniazid, rifampin, and moxifloxacin. PA-824 at 100 mg/kg in cyclodextrin/lecithin was as active as moxifloxacin at 100 mg/kg and isoniazid at 25 mg/kg and was slightly more active than rifampin at 20 mg/kg. Long-term treatment with PA-824 at 100 mg/kg in cyclodextrin/lecithin reduced the bacterial load below 500 CFU in the lungs and spleen. No significant differences in activity between PA-824 and the other single drug treatments tested (isoniazid at 25 mg/kg, rifampin at 10 mg/kg, gatifloxacin at 100 mg/kg, and moxifloxacin at 100 mg/kg) could be observed. In summary, its good activity in in vivo models, as well as its activity against multidrug-resistant
M. tuberculosis
and against
M. tuberculosis
isolates in a potentially latent state, makes PA-824 an attractive drug candidate for the therapy of tuberculosis. These data indicate that there is significant potential for effective oral delivery of PA-824 for the treatment of tuberculosis.
Emergence of Macrolide-Resistant
Mycoplasma pneumoniae
with a 23S rRNA Gene Mutation
Authors: Morozumi Miyuki , Hasegawa Keiko , Kobayashi Reiko , Inoue Nagako , Iwata Satoshi , Kuroki Haruo , Kawamura Naohisa , Nakayama Eiichi , Tajima Takeshi , Shimizu Kouichi , Ubukata Kimiko 
Published: May 2005

ABSTRACT

A total of 195
Mycoplasma pneumoniae
strains were isolated from 2,462 clinical specimens collected between April 2002 and March 2004 from pediatric outpatients with respiratory tract infections. Susceptibilities to six macrolide antibiotics (ML), telithromycin, minocycline, levofloxacin, and sitafloxacin were determined by the microdilution method using PPLO broth. A total of 183
M. pneumoniae
isolates were susceptible to all agents and had excellent MIC
90
s in the following order: 0.00195 μg/ml for azithromycin and telithromycin, 0.0078 μg/ml for clarithromycin, 0.0156 μg/ml for erythromycin, 0.0625 μg/ml for sitafloxacin, 0.5 μg/ml for minocycline, and 1 μg/ml for levofloxacin. Notably, 12 ML-resistant
M. pneumoniae
strains were isolated from patients with pneumonia (10 strains) or acute bronchitis (2 strains). These strains showed resistance to ML with MICs of ≥1 μg/ml, except to rokitamycin. Transition mutations of A2063G or A2064G, which correspond to A2058 and A2059 in
Escherichia coli
, in domain V on the 23S rRNA gene in 11 ML-resistant strains were identified. By pulsed-field gel electrophoresis typing, these strains were classified into groups I and Vb, as described previously (A. Cousin-Allery, A. Charron, B. D. Barbeyrac, G. Fremy, J. S. Jensen, H. Renaudin, and C. Bebear, Epidemiol. Infect.
124:
103-111, 2000). These findings suggest that excessive usage of MLs acts as a trigger to select mutations on the corresponding 23S rRNA gene with the resultant occurrence of ML-resistant
M. pneumoniae
. Monitoring ML susceptibilities for
M. pneumoniae
is necessary in the future.
Combination of Antimicrobial and Endotoxin-Neutralizing Activities of Novel Oleoylamines
Authors: Zorko Mateja , Majerle Andreja , Šarlah David , Keber Mateja Manček , Mohar Barbara , Jerala Roman 
Published: May 2005

ABSTRACTA combination of antimicrobial and endotoxin-neutralizing activities is desired in order to prevent progression from infection to sepsis due to the release of lipopolysaccharide from dying gram-negative bacteria. Lipopolyamines have emerged as a new type of endotoxin-neutralizing compound, but their antimicrobial activity has not been investigated. We synthesized a series of 10 oleoylamines differing in the polyamino head group, particularly in the number and separation between nitrogen atoms and the position of the oleoyl moiety. Compounds showed activity against both gram-negative and gram-positive bacteria in the micromolar range. Compounds were able to provide penetration of ethidium bromide into bacteria, indicating effects on the bacterial membrane. Oleoylamines neutralized endotoxin inLimulusamoebocyte lysate assays and by neutralization of tumor necrosis factor alpha release in human blood. Comparison of biological activities of compounds identified structural properties responsible for antimicrobial activity, and quantitative structure-property relationship analysis provided a quantitative model for prediction of activity of oleoylamines.