bluuebunny/crossref_metadata_2025_split huggingface dataset:
Critique of The American Cancer Society Guidelines for Breast Cancer Screening: Update 2003
Authors: Goolsby Mary Jo , Ricalde Leilani 
Published: May 2005

AbstractThe American Cancer Society Guidelines for Breast Cancer Screening: Update 2003 was obtained through the National Guideline Clearinghouse Web site and was critiqued for potential incorporation into practice. The updated guidelines address screening mammography, physical examination, and new technologies and describe how these may be applied to women at average risk, women at high risk, and older women. The new guidelines emphasize educating women and having them take a more active role in decision making.
Obesity in Youth: Implications for the Advanced Practice Nurse in Primary Care
Authors: Berry Diane , Galasso Pamela , Melkus Gail , Grey Margaret 
Published: May 2005

PurposeTo discuss the advanced practice nurse's diagnosis and management of obesity in youth in primary care.Data SourcesReview of current scientific literature, practice guidelines, and a case study.ConclusionsObesity in youth is difficult to manage. Recent research suggests a genetic and environmental etiology associated with impaired glucose tolerance, type 2 diabetes, hypertension, hyperlipidemia, and hypertriglyceridemia. Nutrition education, increasing physical activity, decreasing sedentary behaviors, and behavioral modification have been used with varying success. Management is directed at healthy lifestyle behavior change for youth and their families.Implications for PracticeIf obesity, impaired glucose tolerance, hypertension, hypercholesterolemia, and hypertriglyceridemia are left untreated, youth may develop type 2 diabetes and coronary artery disease later in life and suffer early morbidity and mortality.
Central Obesity and the Metabolic Syndrome: Implications for Primary Care Providers
Authors: Appel Susan J. , Jones Ellen D. , Kennedy‐Malone Laurie 
Published: May 2005

PurposeTo describe screening measures that will determine which clients are at risk for the metabolic syndrome, common manifestations of the syndrome, preventive diagnostic considerations, and management and treatment options that primary care providers can implement.Data SourcesReview of the clinical and research literature, supple mented with specific diagnostic criteria.ConclusionsCentral obesity is the cornerstone of the metabolic syndrome, which may lead to type 2 diabetes and cardiovascular disease. Generalized obesity is defined body weight that is considerably greater than the ideal weight and that is distributed on all parts of the body. Generalized obesity has long been considered a significant risk factor for developing type 2 diabetes and cardiovascular disease.Those clients of ideal body weight have been considered at less risk for developing these conditions. However, this perception may not always be accurate. Weight distribution plays a major role in acquiring the metabolic syndrome.Because waist circumference is important as overall body weight, central obesity is key determining the risk.Implications for PracticeThe metabolic syndrome has now been given a CPT code (277.7). It is more likely that clients at risk for or with the metabolic syndrome may first be seen by a primary care provider. Primary care providers need to be able to diagnose treat and provide preventive interventions for the metabolic syndrome. Clients at risk will likely be identified during routine health screening. Early detection of and interventions focused on the metabolic syndrome may reduce the occurrence of type 2 diabetes and cardiovascular disease. Use of a tape measure to determine waist circumference may help the provider to identify at‐risk clients who are of normal weight and thus not previously believed to be at risk, as well as those more obviously at risk. It is necessary to determine not only patients' overall body weight but also their waist circumference. A measuring tape may be the key tool for establishing a patient's early risk for the metabolic syndrome and ultimately for prevention of type 2 diabetes and cardiovascular disease.
Phosphorylation of Ribavirin and Viramidine by Adenosine Kinase and Cytosolic 5′-Nucleotidase II: Implications for Ribavirin Metabolism in Erythrocytes
Authors: Wu Jim Zhen , Larson Gary , Walker Heli , Shim Jae Hoon , Hong Zhi 
Published: May 2005

ABSTRACTMany nucleoside analog drugs, such as ribavirin and viramidine, are activated or metabolized in vivo through 5′-phosphorylation. In this report, we determined the steady-state kinetic parameters for 5′-monophosphorylation of ribavirin and viramidine by adenosine kinase. The apparentKmfor ribavirin is 540 μM, andkcatis 1.8 min−1. Its catalytic efficiency of 3.3 × 10−3min−1· μM−1is 1,200-fold lower than that of adenosine. In contrast to the common belief that ribavirin is exclusively phosphorylated by adenosine kinase, cytosolic 5′-nucleotidase II was found to catalyze ribavirin phosphorylation in vitro. The reaction is optimally stimulated by the physiological concentration of ATP or 2,3-bisphosphoglycerate. In phosphate-buffered saline plus ATP and 2,3-bisphosphoglycerate, the apparentKmfor ribavirin is 88 μM, andkcatis 4.0 min−1. These findings suggest that cytosolic 5′-nucleotidase II may be involved in ribavirin phosphorylation in vivo. Like ribavirin, viramidine was found to be phosphorylated by either adenosine kinase or cytosolic 5′-nucleotidase II, albeit with a much lower activity. The catalytic efficiency for viramidine phosphorylation is 10- to 330-fold lower than that of ribavirin, suggesting that other nucleoside kinase(s) may be involved in viramidine phosphorylation in vivo. Both ribavirin and viramidine are not phosphorylated by deoxycytidine kinase and uridine-cytidine kinase. The coincidence of presence of high concentrated 2,3-bisphosphoglycerate in erythrocytes suggests that cytosolic 5′-nucleotidase II could play an important role in phosphorylating ribavirin and contribute to anabolism of ribavirin triphosphate in erythrocytes. Elucidation of ribavirin and viramidine phosphorylation mechanism should shed light on their in vivo metabolism, especially the ribavirin-induced hemolytic anemia in erythrocytes.
Are Transporter Genes Other than the Chloroquine Resistance Locus (
pfcrt
) and Multidrug Resistance Gene (
pfmdr
) Associated with Antimalarial Drug Resistance?
Authors: Anderson Timothy J. C. , Nair Shalini , Qin Huang , Singlam Sittaporn , Brockman Alan , Paiphun Lucy , Nosten François 
Published: May 2005

ABSTRACT

Mu et al. (Mu, J., M. T. Ferdig, X. Feng, D. A. Joy, J. Duan, T. Furuya, G. Subramanian, L. Aravind, R. A. Cooper, J. C. Wootton, M. Xiong, and X. Z. Su, Mol. Microbiol.
49:
977-989, 2003) recently reported exciting associations between nine new candidate transporter genes and in vitro resistance to chloroquine (CQ) and quinine (QN), with six of these loci showing association with CQ or QN in a southeast Asian population sample. We replicated and extended this work by examining polymorphisms in these genes and in vitro resistance to eight drugs in parasites collected from the Thailand-Burma border. To minimize problems of multiple testing, we used a two-phase study design, while to minimize problems caused by population structure, we analyzed parasite isolates collected from a single clinic. We first examined associations between genotype and drug response in 108 unique single-clone parasite isolates. We found strong associations between single nucleotide polymorphisms in
pfmdr
and mefloquine (MFQ), artesunate (AS), and lumefantrine (LUM) response. We also observed associations between an ABC transporter (G7) and response to QN and AS and between another ABC transporter (G49) and response to dihydro-artemisinin (DHA). We reexamined significant associations in an independent sample of 199 unique single-clone infections from the same location. The significant associations with
pfmdr-
1042 detected in the first survey remained. However, with the exception of the G7-artesunate association, all other associations observed with the nine new candidate transporters disappeared. We also examined linkage disequilibrium (LD) between markers and phenotypic correlations between drug responses. We found minimal LD between genes. Furthermore, we found no correlation between chloroquine and quinine responses, although we did find expected strong correlations between MFQ, QN, AS, DHA, and LUM. To conclude, we found no evidence for an association between 8/9 candidate genes and response to eight different antimalarial drugs. However, the consistent association observed between a 3-bp indel in G7 and AS response merits further investigation.
Phenotypic and Molecular Characterization of
Mycobacterium tuberculosis
Isolates Resistant to both Isoniazid and Ethambutol
Authors: Parsons Linda M. , Salfinger Max , Clobridge Anne , Dormandy Jillian , Mirabello Lisa , Polletta Valerie L. , Sanic Ahmet , Sinyavskiy Oleg , Larsen Susan C. , Driscoll Jeffrey , Zickas Genet , Taber Harry W. 
Published: May 2005

ABSTRACT

In performing radiometric susceptibility testing on over 2,000 patient isolates of
Mycobacterium tuberculosis
during the past 6 years, we found that resistance to 7.5 μg/ml ethambutol (EMB) occurred only in isolates that are also resistant to 0.4 μg/ml isoniazid (INH). Using 157 selected isolates in the present study, we performed radiometric and agar proportion susceptibility tests and DNA sequencing of genetic regions associated with resistance to these two drugs. The goal was to study the occurrence of the common mutations associated with resistance to each drug and also to determine whether any particular INH-resistance-associated mutation occurred more often in combination with any particular EMB-resistance-associated mutation. In an analysis of 128 isolates resistant to 0.4 μg/ml INH, we found that a mutation at
katG
Ser315 was more common in isolates also resistant to 7.5 μg/ml EMB (61 of 67 = 91.0%) than in isolates either susceptible to EMB or resistant to 2.5 μg/ml EMB (39 of 60 = 65.0%). These observations suggest that INH-resistant strains with a mutation at
katG
Ser315 are more likely to acquire resistance to 7.5 μg/ml EMB than are isolates with INH-resistance-associated mutations at other sites. In addition, we found that 64 of 67 (95.5%) isolates resistant to 7.5 μg/ml EMB contained a mutation in either codon 306 or codon 406 of
embB.
Met306Val was the most common
embB
mutation, present in 52 (77.6%) of the 67 isolates. Most occurrences of this mutation (49 of 52 = 94.2%) were found in isolates that also contained the
katG
Ser315Thr mutation. Finally, sequencing this region of
embB
appears to be sufficiently sensitive for use as a rapid screening tool for detection of high-level resistance to EMB.
Genome-Wide Expression Profiling of the Response to Azole, Polyene, Echinocandin, and Pyrimidine Antifungal Agents inCandida albicans
Authors: Liu Teresa T. , Lee Robin E. B. , Barker Katherine S. , Lee Richard E. , Wei Lai , Homayouni Ramin , Rogers P. David 
Published: May 2005

ABSTRACTAntifungal agents exert their activity through a variety of mechanisms, some of which are poorly understood. We examined changes in the gene expression profile ofCandida albicansfollowing exposure to representatives of the four currently available classes of antifungal agents used in the treatment of systemic fungal infections. Ketoconazole exposure increased expression of genes involved in lipid, fatty acid, and sterol metabolism, includingNCP1,MCR1,CYB5,ERG2,ERG3,ERG10,ERG25,ERG251, and that encoding the azole target,ERG11. Ketoconazole also increased expression of several genes associated with azole resistance, includingCDR1,CDR2,IFD4,DDR48, andRTA3. Amphotericin B produced changes in the expression of genes involved in small-molecule transport (ENA21), and in cell stress (YHB1,CTA1,AOX1, andSOD2). Also observed was decreased expression of genes involved in ergosterol biosynthesis, includingERG3andERG11. Caspofungin produced changes in expression of genes encoding cell wall maintenance proteins, including the β-1,3-glucan synthase subunitGSL22, as well asPHR1,ECM21,ECM33, andFEN12. Flucytosine increased the expression of proteins involved in purine and pyrimidine biosynthesis, includingYNK1,FUR1, and that encoding its target,CDC21. Real-time reverse transcription-PCR was used to confirm microarray results. Genes responding similarly to two or more drugs were also identified. These data shed new light on the effects of these classes of antifungal agents onC. albicans.
New Mutations and Horizontal Transfer of
rpoB
among Rifampin-Resistant
Streptococcus pneumoniae
from Four Spanish Hospitals
Authors: Ferrándiz María José , Ardanuy Carmen , Liñares Josefina , García-Arenzana José María , Cercenado Emilia , Fleites Ana , de la Campa Adela G. 
Published: May 2005

ABSTRACT

A total of 103 (0.7%) of 14,236
Streptococcus pneumoniae
isolates collected in four Spanish hospitals from 1989 to 2003 were resistant to rifampin (MICs, 4 to 512 μg/ml). Only sixty-one (59.2%) of these isolates were available for molecular characterization. Resistance was mostly related to human immunodeficiency virus (HIV) infection in adult patients and to conjunctivitis in children. Thirty-six different pulsed-field gel electrophoresis patterns were identified among resistant isolates, five of which were related to international clones (Spain
23F
-1, Spain
6B
-2, Spain
9V
-3, Spain
14
-5, and clone C of serotype 19F), and accounted for 49.2% of resistant isolates. Single sense mutations at cluster N or I of the
rpoB
gene were found in 39 isolates, while double mutations, either at cluster I, at clusters I and II, or at clusters N and III, were found in 14 isolates. The involvement of the mutations in rifampin resistance was confirmed by genetic transformation. Single mutations at clusters N and I conferred MICs of 2 μg/ml and 4 to 32 μg/ml, respectively. Eight isolates showed high degrees of nucleotide sequence variations (2.3 to 10.8%) in
rpoB
, suggesting a recombinational origin for these isolates, for which viridans group streptococci are their potential gene donors. Although the majority of rifampin-resistant isolates were isolated from individual patients without temporal or geographical relationships, the clonal dissemination of rifampin-resistant isolates was observed among 12 HIV-infected patients in the two hospitals with higher rates of resistance.
Transcriptional Response of
Enterococcus faecalis
V583 to Erythromycin
Authors: Aakra Ågot , Vebø Heidi , Snipen Lars , Hirt Helmut , Aastveit Are , Kapur Vivek , Dunny Gary , Murray Barbara , Nes Ingolf F. 
Published: May 2005

ABSTRACT

A transcriptional profile of
Enterococcus faecalis
V583 (V583) treated with erythromycin is presented. This is the first study describing a complete transcriptional profile of
Enterococcus. E. faecalis
is a common and nonvirulent bacterium in many natural environments, but also an important cause of nosocomial infections. We have used a genome-wide microarray based on the genome sequence of V583 to study gene expression in cells exposed to erythromycin. V583 is resistant to relatively high concentrations of erythromycin, but growth is retarded by the treatment. The effect of erythromycin treatment on V583 was studied by a time course experiment; samples were extracted at five time points over a period of 90 min. A drastic change in gene transcription was seen with the erythromycin-treated cells compared to the untreated cells. Altogether, 260 genes were down-regulated at one or more time points, while 340 genes were up-regulated. Genes encoding hypothetical proteins and genes encoding transport and binding proteins were the two most dominating groups of differentially expressed genes. The gene encoding
ermB
(EFA0007) was expressed, but not differentially, which indicated that other genes are important for the survival and growth maintenance of V583 treated with erythromycin. One of these genes is a putative MsrC-like protein, which was up-regulated at all time points studied. Other specific genes that were found to be up-regulated were genes encoding ABC transporters and two-component regulatory systems, and these may be genes that are important for the specific response of V583 to erythromycin.
Linezolid versus Vancomycin in Treatment of Complicated Skin and Soft Tissue Infections
Authors: Weigelt John , Itani Kamal , Stevens Dennis , Lau William , Dryden Matthew , Knirsch Charles 
Published: May 2005

ABSTRACT

Skin and soft tissue infections (SSTIs) are a common cause of morbidity in both the community and the hospital. An SSTI is classified as complicated if the infection has spread to the deeper soft tissues, if surgical intervention is necessary, or if the patient has a comorbid condition hindering treatment response (e.g., diabetes mellitus or human immunodeficiency virus). The purpose of this study was to compare linezolid to vancomycin in the treatment of suspected or proven methicillin-resistant gram-positive complicated SSTIs (CSSTIs) requiring hospitalization. This was a randomized, open-label, comparator-controlled, multicenter, multinational study that included patients with suspected or proven methicillin-resistant
Staphylococcus aureus
(MRSA) infections that involved substantial areas of skin or deeper soft tissues, such as cellulitis, abscesses, infected ulcers, or burns (<10% of total body surface area). Patients were randomized (1:1) to receive linezolid (600 mg) every 12 h either intravenously (i.v.) or orally or vancomycin (1 g) every 12 h i.v. In the intent-to-treat population, 92.2% and 88.5% of patients treated with linezolid and vancomycin, respectively, were clinically cured at the test-of-cure (TOC) visit (
P
= 0.057). Linezolid outcomes (124/140 patients or 88.6%) were superior to vancomycin outcomes (97/145 patients or 66.9%) at the TOC visit for patients with MRSA infections (
P
< 0.001). Drug-related adverse events were reported in similar numbers in both the linezolid and the vancomycin arms of the trial. The results of this study demonstrate that linezolid therapy is well tolerated, equivalent to vancomycin in treating CSSTIs, and superior to vancomycin in the treatment of CSSTIs due to MRSA.
Inducible Clindamycin Resistance and Molecular Epidemiologic Trends of Pediatric Community-Acquired Methicillin-Resistant
Staphylococcus aureus
in Dallas, Texas
Authors: Chavez-Bueno Susana , Bozdogan Bülent , Katz Kathy , Bowlware Karen L. , Cushion Nancy , Cavuoti Dominick , Ahmad Naveed , McCracken George H. , Appelbaum Peter C. 
Published: May 2005

ABSTRACT

Community-acquired methicillin-resistant
Staphylococcus aureus
(CA-MRSA) infection occurs commonly in children. Clindamycin resistance may be inducible or constitutive, and the rates of inducible resistance in CA-MRSA that could produce clindamycin treatment failures vary worldwide. The double-disk test was performed in 197 erythromycin-resistant and clindamycin-susceptible CA-MRSA strains from children in Dallas, Texas, from 1999 to 2002 to determine inducible clindamycin resistance. Resistance mechanisms were studied by PCR; epidemiologic trends were studied by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Inducible resistance was demonstrated in 28 (93% ±6%) of 30 tested isolates in 1999, 21 (64%, ±11%) of 33 in 2000, 12 (23% ±7%) of 52 in 2001, and 6 (7% ±3%) of 82 in 2002. All noninducible strains had the
msr
(A) gene. Among inducible resistant strains, 31 had
erm
(B), 24 had
erm
(C), and 12 had
erm
(A) genes. Two distinct pulsed types were the most prevalent; one of them was the most common pulsed type in 1999, whereas in 2002 a different pulsed type was prevalent. MLST analyses determined that ST-8 was the most common type, with 76% ±5% found in 2002. All but one of these clindamycin-susceptible, erythromycin-resistant ST-8 strains showed no induction of clindamycin resistance. We conclude that, among erythromycin-resistant, clindamycin-susceptible CA-MRSA strains isolated from children in Dallas, inducible methylase resistance became less common from 1999 to 2002 (
P
< 0.001). The phenotype of strains was associated with their sequence type. Our results demonstrate a clonal shift in CA-MRSA in Dallas children from 1999 to 2002.
Bactericidal Activity of the Nitroimidazopyran PA-824 in a Murine Model of Tuberculosis
Authors: Tyagi Sandeep , Nuermberger E. , Yoshimatsu T. , Williams K. , Rosenthal I. , Lounis N. , Bishai W. , Grosset J. 
Published: May 2005

ABSTRACT

The nitroimidazopyran PA-824 has potent in vitro activity against
Mycobacterium tuberculosis
, a narrow spectrum of activity limited primarily to the
M. tuberculosis
complex, and no demonstrable cross-resistance to a variety of antituberculosis drugs. In a series of experiments, we sequentially characterized the activity of PA-824 in an experimental murine model of tuberculosis. The minimal effective dose was 12.5 mg/kg of body weight/day. The minimal bactericidal dose (MBD) was 100 mg/kg/day. When PA-824 was used as monotherapy at the MBD, it exhibited promising bactericidal activity during the initial intensive phase of therapy that was similar to that of the equipotent dose of isoniazid in humans. In combination with isoniazid, PA-824 prevented the selection of isoniazid-resistant mutants. Perhaps more importantly, PA-824 also demonstrated potent activity during the continuation phase of therapy, during which it targeted bacilli that had persisted through an initial 2-month intensive phase of treatment with rifampin, isoniazid, and pyrazinamide. Together, these data strongly support further evaluation of PA-824 in combination with first- or second-line antituberculosis drugs to determine its potential contribution to the treatment of drug-susceptible or multidrug-resistant tuberculosis, respectively.
TMC114, a Novel Human Immunodeficiency Virus Type 1 Protease Inhibitor Active against Protease Inhibitor-Resistant Viruses, Including a Broad Range of Clinical Isolates
Authors: De Meyer Sandra , Azijn Hilde , Surleraux Dominique , Jochmans Dirk , Tahri Abdellah , Pauwels Rudi , Wigerinck Piet , de Béthune Marie-Pierre 
Published: May 2005

ABSTRACT

The purpose of this study was to characterize the antiviral activity, cytotoxicity, and mechanism of action of TMC114, a novel human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI). TMC114 exhibited potent anti-HIV activity with a 50% effective concentration (EC
50
) of 1 to 5 nM and a 90% effective concentration of 2.7 to 13 nM. TMC114 exhibited no cytotoxicity at concentrations up to 100 μM (selectivity index, >20,000). All viruses in a panel of 19 recombinant clinical isolates carrying multiple protease mutations and demonstrating resistance to an average of five other PIs, were susceptible to TMC114, defined as a fold change in EC
50
of <4. TMC114 was also effective against the majority of 1,501 PI-resistant recombinant viruses derived from recent clinical samples, with EC
50
s of <10 nM for 75% of the samples. In sequential passage experiments using HIV-1 LAI, two mutations (R41T and K70E) were selected. One selected virus showed a 10-fold reduction in susceptibility to TMC114, but <10-fold reductions in susceptibility to the current PIs (atazanavir was not assessed), except saquinavir. However, when the selected mutations were introduced into a laboratory strain by site-directed mutagenesis, they had no effect on susceptibility to TMC114 or other PIs. There was no evidence of antagonism between TMC114 and any currently available PIs or reverse transcriptase inhibitors. Combinations with ritonavir, nelfinavir, and amprenavir showed some evidence of synergy. These results suggest that TMC114 is a potential candidate for the treatment of both naïve and PI-experienced patients with HIV.