bluuebunny/crossref_metadata_2025 huggingface dataset:
A toolkit for rapid gene mapping in the nematode Caenorhabditis briggsae
Authors: Koboldt Daniel C , Staisch Julia , Thillainathan Bavithra , Haines Karen , Baird Scott E , Chamberlin Helen M , Haag Eric S , Miller Raymond D , Gupta Bhagwati P
Published: May 2010

Background

The nematode C. briggsae serves as a useful model organism for comparative analysis of developmental and behavioral processes. The amenability of C. briggsae to genetic manipulations and the availability of its genome sequence have prompted researchers to study evolutionary changes in gene function and signaling pathways. These studies rely on the availability of forward genetic tools such as mutants and mapping markers.

Results

We have computationally identified more than 30,000 polymorphisms (SNPs and indels) in C. briggsae strains AF16 and HK104. These include 1,363 SNPs that change restriction enzyme recognition sites (snip-SNPs) and 638 indels that range between 7 bp and 2 kb. We established bulk segregant and single animal-based PCR assay conditions and used these to test 107 polymorphisms. A total of 75 polymorphisms, consisting of 14 snip-SNPs and 61 indels, were experimentally confirmed with an overall success rate of 83%. The utility of polymorphisms in genetic studies was demonstrated by successful mapping of 12 mutations, including 5 that were localized to sub-chromosomal regions. Our mapping experiments have also revealed one case of a misassembled contig on chromosome 3.

Conclusions

We report a comprehensive set of polymorphisms in C. briggsae wild-type strains and demonstrate their use in mapping mutations. We also show that molecular markers can be useful tools to improve the C. briggsae genome sequence assembly. Our polymorphism resource promises to accelerate genetic and functional studies of C. briggsae genes.
Epigenetic chromatin modifiers in barley: IV. The study of barley Polycomb group (PcG) genes during seed development and in response to external ABA
Authors: Kapazoglou Aliki , Tondelli Alessandro , Papaefthimiou Dimitra , Ampatzidou Helen , Francia Enrico , Stanca Michele A , Bladenopoulos Konstantinos , Tsaftaris Athanasios S
Published: May 2010

Background

Epigenetic phenomena have been associated with the regulation of active and silent chromatin states achieved by modifications of chromatin structure through DNA methylation, and histone post-translational modifications. The latter is accomplished, in part, through the action of PcG (Polycomb group) protein complexes which methylate nucleosomal histone tails at specific sites, ultimately leading to chromatin compaction and gene silencing. Different PcG complex variants operating during different developmental stages have been described in plants. In particular, the so-called FIE/MEA/FIS2 complex governs the expression of genes important in embryo and endosperm development in Arabidopsis. In our effort to understand the epigenetic mechanisms regulating seed development in barley (Hordeum vulgare), an agronomically important monocot plant cultivated for its endosperm, we set out to characterize the genes encoding barley PcG proteins.

Results

Four barley PcG gene homologues, named HvFIE, HvE(Z), HvSu(z)12a, and HvSu(z)12b were identified and structurally and phylogenetically characterized. The corresponding genes HvFIE, HvE(Z), HvSu(z)12a, and HvSu(z)12b were mapped onto barley chromosomes 7H, 4H, 2H and 5H, respectively. Expression analysis of the PcG genes revealed significant differences in gene expression among tissues and seed developmental stages and between barley cultivars with varying seed size. Furthermore, HvFIE and HvE(Z) gene expression was responsive to the abiotic stress-related hormone abscisic acid (ABA) known to be involved in seed maturation, dormancy and germination.

Conclusion

This study reports the first characterization of the PcG homologues, HvFIE, HvE(Z), HvSu(z)12a and HvSu(z)12b in barley. All genes co-localized with known chromosomal regions responsible for malting quality related traits, suggesting that they might be used for developing molecular markers to be applied in marker assisted selection. The PcG differential expression pattern in different tissues and seed developmental stages as well as in two barley cultivars with different seed size is suggestive of a role for these genes in barley seed development. HvFIE and HvE(Z) were also found to be induced by the plant hormone ABA implying an association with ABA-mediated processes during seed development, germination and stress response.
Large screening of CA-MRSA among Staphylococcus aureus colonizing healthy young children living in two areas (urban and rural) of Portugal
Authors: Tavares Débora A , Sá-Leão Raquel , Miragaia Maria , de Lencastre Hermínia
Published: May 2010

Background

The incidence of pediatric infections due to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), including children with no identifiable risk factors, has increased worldwide in the last decade. This suggests that healthy children may constitute a reservoir of MRSA in the community. In this study, nested within a larger one on nasopharyngeal ecology, we aimed to: (i) evaluate the prevalence of MRSA colonizing young children in Portugal; and (ii) compare results with those obtained in a study conducted a decade ago, when this prevalence was <0.5%.

Methods

In the years 2006, 2007, and 2009, nasopharyngeal samples were obtained from 2,100 children aged up to 6 years attending day-care centers. S. aureus were isolated by routine procedures and strains were tested for susceptibility against a panel of 12 antimicrobial agents. MRSA isolates were further characterized by SmaI-PFGE profiling, MLST, spa typing, SCCmec typing, and presence of virulence factors.

Results

Seventeen percent of the children carried S. aureus. Among the 365 isolates, non-susceptibility rates were 88% to penicillin, 14% to erythromycin, 6% to clindamycin, 2% to tetracycline, and <1% to oxacillin, rifampicin, ciprofloxacin, and SXT. Three MRSA strains were isolated. These had properties of CA-MRSA, such as low-level resistance to oxacillin and limited resistance to non-beta-lactams. Two CA-MRSA were related to USA700 (ST72-IV): one was ST72-IVc, spa type t148; the other was ST939-IVa (ST939 is a single locus variant (SLV) of ST72), spa type t324. The third strain was related to USA300 (ST8-IV) being characterized by ST931 (SLV of ST8)-VI, spa type t008. The three MRSA strains were PVL-negative, but all carried LukE-LukD leukocidin, hemolysins gamma, gamma variant and beta, and staphylococcal enterotoxin sel.

Conclusions

Our results, based on analysis of S. aureus isolated from nasopharyngeal samples, suggest that in Portugal the prevalence of CA-MRSA carriage in healthy young children remains extremely low favoring the exclusion of this group as a reservoir of such isolates.
POLG1 p.R722H mutation associated with multiple mtDNA deletions and a neurological phenotype
Authors: Komulainen Tuomas , Hinttala Reetta , Kärppä Mikko , Pajunen Leila , Finnilä Saara , Tuominen Hannu , Rantala Heikki , Hassinen Ilmo , Majamaa Kari , Uusimaa Johanna
Published: May 2010

Background

The c.2447G>A (p.R722H) mutation in the gene POLG1 of the catalytic subunit of human mitochondrial polymerase gamma has been previously found in a few occasions but its pathogenicity has remained uncertain. We set out to ascertain its contribution to neuromuscular disease.

Methods

Probands from two families with probable mitochondrial disease were examined clinically, muscle and buccal epithelial DNA were analyzed for mtDNA deletions, and the POLG1, POLG2, ANT1 and Twinkle genes were sequenced.

Results

An adult proband presented with progressive external ophthalmoplegia, sensorineural hearing impairment, diabetes mellitus, dysphagia, a limb myopathy and dementia. Brain MRI showed central and cortical atrophy, and 18F-deoxyglucose PET revealed reduced glucose uptake. Histochemical analysis of muscle disclosed ragged red fibers and cytochrome c oxidase-negative fibers. Electron microscopy showed subsarcolemmal aggregates of morphologically normal mitochondria. Multiple mtDNA deletions were found in the muscle, and sequencing of the POLG1 gene revealed a homozygous c.2447G>A (p.R722H) mutation. His two siblings were also homozygous with respect to the p.R722H mutation and presented with dementia and sensorineural hearing impairment. In another family the p.R722H mutation was found as compound heterozygosity with the common p.W748S mutation in two siblings with mental retardation, ptosis, epilepsy and psychiatric symptoms. The estimated carrier frequency of the p.R722H mutation was 1:135 in the Finnish population. No mutations in POLG2, ANT1 and Twinkle genes were found. Analysis of the POLG1 sequence by homology modeling supported the notion that the p.R722H mutation is pathogenic.

Conclusions

The recessive c.2447G>A (p.R722H) mutation in the linker region of the POLG1 gene is pathogenic for multiple mtDNA deletions in muscle and is associated with a late-onset neurological phenotype as a homozygous state. The onset of the disease can be earlier in compound heterozygotes.
Increased concentration of two different advanced glycation end-products detected by enzyme immunoassays with new monoclonal antibodies in sera of patients with rheumatoid arthritis
Authors: Vytášek Richard , Šedová Liliana , Vilím Vladimír
Published: May 2010

Background

Levels of pentosidine (representative of advanced glycation end-products) in sera of patients with rheumatoid arthritis are increased when compared with sera of other diagnoses or healthy controls. These levels have been reported to correlate with clinical indices of rheumatoid arthritis activity and with laboratory markers of inflammation. The purpose of this study was to find out if these findings pertain to other advanced glycation end-products.

Methods

We have developed two immunoassays based on new monoclonal antibodies to advanced glycation end-products. Antibody 103-E3 reacts with an unidentified antigen, formed in the reaction of proteins with ribose, while antibody 8-C1 responds to Nε-(carboxyethyl)lysine. We have used these monoclonal antibodies to measure levels of advanced glycation end-products in sera of patients with rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, and healthy controls. We calculated the correlations between advanced glycation end-product levels in rheumatoid arthritis sera and the Disease Activity Score 28 (DAS28), age, disease duration, CRP, anti-CCP, rheumatoid factor and treatment with corticosteroids, respectively.

Results

Levels of both glycation products were significantly higher in sera of patients with rheumatoid arthritis when compared with sera of patients with systemic lupus erythematosus, osteoarthritis, or the healthy controls. Neither the level of Nε-(carboxyethyl)lysine nor the level of the 103-E3 antigen in rheumatoid arthritis sera correlated with the DAS28-scored rheumatoid arthritis activity. The levels of both antigens in rheumatoid arthritis sera did not correlate with age, gender, corticosteroid treatment, or levels of CRP, anti-CCP antibodies, and rheumatoid factor in sera.

Conclusions

We report highly specific increases in the levels of two advanced glycation end-products in sera of patients with rheumatoid arthritis. This increase could be explained neither by rheumatoid arthritis activity nor by inflammation. We propose a working hypothesis that presumes the existence of a link between advanced glycation end-product formation and induction of autoimmunity.
Social determinants of prescribed and non-prescribed medicine use
Authors: Daban Ferran , Pasarín M Isabel , Rodríguez-Sanz Maica , García-Altés Anna , Villalbí Joan R , Zara Corinne , Borrell Carme
Published: May 2010

Background

The aim of the present study was to describe the use of prescribed and non prescribed medicines in a non-institutionalised population older than 15 years of an urban area during the year 2000, in terms of age and gender, social class, employment status and type of Primary Health Care.

Methods

Cross-sectional study. Information came from the 2000 Barcelona Health Interview Survey. The indicators used were the prevalence of use of prescribed and non-prescribed medicines in the two weeks prior to the interview. Descriptive analyses, bivariate and multivariate logistic regression analyses were carried out.

Results

More women than men took medicines (75.8%vs. 60% respectively). The prevalence of use of prescribed medicines increased with age while the prevalence of non-prescribed use decreased. These age differences are smaller among those with poor perceived health. In terms of social class, a higher percentage of men with good health in the more advantaged classes took non-prescribed medicines compared with disadvantaged classes (38.7% vs 31.8%). In contrast, among the group with poor health, more people from the more advantaged classes took prescribed medicines, compared with disadvantaged classes (51.4% vs 33.3%). A higher proportion of people who were either retired, unemployed or students, with good health, used prescribed medicines.

Conclusion

This study shows that beside health needs, there are social determinants affecting medicine consumption in the city of Barcelona.
Differential chemosensitization of P-glycoprotein overexpressing K562/Adr cells by withaferin A and Siamois polyphenols
Authors: Suttana Wipob , Mankhetkorn Samlee , Poompimon Wilart , Palagani Ajay , Zhokhov Sergey , Gerlo Sarah , Haegeman Guy , Berghe Wim Vanden
Published: May 2010

Background

Multidrug resistance (MDR) is a major obstacle in cancer treatment and is often the result of overexpression of the drug efflux protein, P-glycoprotein (P-gp), as a consequence of hyperactivation of NFκB, AP1 and Nrf2 transcription factors. In addition to effluxing chemotherapeutic drugs, P-gp also plays a specific role in blocking caspase-dependent apoptotic pathways. One feature that cytotoxic treatments of cancer have in common is activation of the transcription factor NFκB, which regulates inflammation, cell survival and P-gp expression and suppresses the apoptotic potential of chemotherapeutic agents. As such, NFκB inhibitors may promote apoptosis in cancer cells and could be used to overcome resistance to chemotherapeutic agents.

Results

Although the natural withanolide withaferin A and polyphenol quercetin, show comparable inhibition of NFκB target genes (involved in inflammation, angiogenesis, cell cycle, metastasis, anti-apoptosis and multidrug resistance) in doxorubicin-sensitive K562 and -resistant K562/Adr cells, only withaferin A can overcome attenuated caspase activation and apoptosis in K562/Adr cells, whereas quercetin-dependent caspase activation and apoptosis is delayed only. Interestingly, although withaferin A and quercetin treatments both decrease intracellular protein levels of Bcl2, Bim and P-Bad, only withaferin A decreases protein levels of cytoskeletal tubulin, concomitantly with potent PARP cleavage, caspase 3 activation and apoptosis, at least in part via a direct thiol oxidation mechanism.

Conclusions

This demonstrates that different classes of natural NFκB inhibitors can show different chemosensitizing effects in P-gp overexpressing cancer cells with impaired caspase activation and attenuated apoptosis.
Use of cracked maize as a carrier for NDV4 vaccine in experimental vaccination of chickens
Authors: Olabode Atanda O , Ndako James A , Echeonwu Georgebest ON , Nwankiti Obinna O , Chukwuedo Anthony A
Published: May 2010

The suitability of V4 vaccine coated on cracked local grain (maize) and its husks and used for oral vaccination of chickens was assessed. Seventy-two (72) birds aged three (3) weeks and above were divided into six groups of twelve (12) birds per group. The birds were bled to determine their prevaccination HI antibody status while five different samples of cracked maize were coated with the V4 vaccine and fed to the chickens orally in each of the groups. All birds in the group including the controls were bled at 7, 14 and 21 days post vaccination to determine the presence and level of antibody response in each of the groups. Results obtained showed that prevaccination haemagglutination inhibition (HI) titre was less than two (log2) in 18% of the birds used in this experiment, however 14% of the birds had an HI titre of ≤ 4. The post vaccination antibody titre showed that birds vaccinated with vaccine coated maize gave a post vaccination HI antibody titre of between Log2(6-8). when the coated maize samples were soaked in water at room temperature and assessed after 24 hours, the treated maize parts gave >6.3 log10 EID50 and above while the untreated parts gave < 3.0 log10 EID50. The experiment showed that whole maize and husks, which were not treated, may contain agents which are virus inhibitory. Form this research the treated maize which was soaked and washed gave a higher geometric mean titre, hence tends to be good carriers of the virus (vaccine). It is therefore concluded from this work that processed cracked maize could be a good carrier of NDV4 vaccine. It is hereby recommended that only treated maize could be used as carrier for the V4 vaccine.
Genomics and proteomics approaches to the study of cancer-stroma interactions
Authors: Rodrigues-Lisoni Flávia C , Peitl Paulo , Vidotto Alessandra , Polachini Giovana M , Maniglia José V , Carmona-Raphe Juliana , Cunha Bianca R , Henrique Tiago , Souza Caique F , Teixeira Rodrigo AP , Fukuyama Erica E , Michaluart Pedro , de Carvalho Marcos B , Oliani Sonia M ,   Head and Neck Genome Project GENCAPO, Tajara Eloiza H
Published: May 2010

Background

The development and progression of cancer depend on its genetic characteristics as well as on the interactions with its microenvironment. Understanding these interactions may contribute to diagnostic and prognostic evaluations and to the development of new cancer therapies. Aiming to investigate potential mechanisms by which the tumor microenvironment might contribute to a cancer phenotype, we evaluated soluble paracrine factors produced by stromal and neoplastic cells which may influence proliferation and gene and protein expression.

Methods

The study was carried out on the epithelial cancer cell line (Hep-2) and fibroblasts isolated from a primary oral cancer. We combined a conditioned-medium technique with subtraction hybridization approach, quantitative PCR and proteomics, in order to evaluate gene and protein expression influenced by soluble paracrine factors produced by stromal and neoplastic cells.

Results

We observed that conditioned medium from fibroblast cultures (FCM) inhibited proliferation and induced apoptosis in Hep-2 cells. In neoplastic cells, 41 genes and 5 proteins exhibited changes in expression levels in response to FCM and, in fibroblasts, 17 genes and 2 proteins showed down-regulation in response to conditioned medium from Hep-2 cells (HCM). Nine genes were selected and the expression results of 6 down-regulated genes (ARID4A, CALR, GNB2L1, RNF10, SQSTM1, USP9X) were validated by real time PCR.

Conclusions

A significant and common denominator in the results was the potential induction of signaling changes associated with immune or inflammatory response in the absence of a specific protein.
Estrogen Alone in Postmenopausal Women and Breast Cancer Detection by Means of Mammography and Breast Biopsy
Authors: Chlebowski Rowan T. , Anderson Garnet , Manson JoAnn E. , Pettinger Mary , Yasmeen Shagufta , Lane Dorothy , Langer Robert D. , Hubbell F. Allan , McTiernan Anne , Hendrix Susan , Schenken Robert , Stefanick Marcia L.
Published: May 2010

Purpose

As the influence of estrogen alone on breast cancer detection is not established, we examined this issue in the Women's Health Initiative trial, which randomly assigned 10,739 postmenopausal women with prior hysterectomy to conjugated equine estrogen (CEE; 0.625 mg/d) or placebo.

Methods

Screening mammography and breast exams were performed at baseline and annually. Breast biopsies were based on clinical findings. Effects of CEE alone on breast cancer detection were determined by using receiver operating characteristic (ROC) analyses of mammogram performance.

Results

After a 7.1-year mean follow-up, fewer invasive breast cancers were diagnosed in the CEE than in the placebo group, but the difference was not statistically significant. Use of CEE alone increased mammograms with short-interval follow-up recommendations (cumulative, 39.2% v 29.6.3%; P < .001) but not abnormal mammograms (ie, those suggestive of or highly suggestive of malignancy; cumulative, 7.3% v 7.0%; P = .41). Breast biopsies were more frequent in the CEE group (cumulative, 12.5% v 10.7%; P = .004) and less commonly diagnosed as cancer (8.9% v 15.8%, respectively, with positive biopsies; P = .04). Mammographic breast cancer detection in the CEE group was significantly compromised only in the early years of use.

Conclusion

CEE alone use for 5 years results in approximately one in 11 and one in 50 women having otherwise avoidable mammograms with short-interval follow-up recommendations or breast biopsies, respectively. Although the breast biopsies on CEE were less commonly diagnosed as cancer, breast cancer detection was not substantially compromised. These findings differ from estrogen-plus-progestin use, for which significantly increased abnormal mammograms and a compromise in breast cancer detection are seen.
Cytogenetics of Childhood Acute Myeloid Leukemia: United Kingdom Medical Research Council Treatment Trials AML 10 and 12
Authors: Harrison Christine J. , Hills Robert K. , Moorman Anthony V. , Grimwade David J. , Hann Ian , Webb David K.H. , Wheatley Keith , de Graaf Siebold S.N. , van den Berg Eva , Burnett Alan K. , Gibson Brenda E.S.
Published: May 2010

Purpose

Karyotype is an independent indicator of prognosis in acute myeloid leukemia (AML) that is widely applied to risk-adapted therapy. Because AML is rare in children, the true prognostic significance of individual chromosomal abnormalities in this age group remains unclear.

Patients and Methods

This cytogenetic study of 729 childhood patients classified them into 22 subgroups and evaluated their incidence and risk.

Results

Rearrangements of 11q23 were the most frequent abnormality found in approximately 16% of patients, with 50% of these in infants. The outcome for all patients with 11q23 abnormalities was intermediate; no difference was observed for those with t(9;11)(p21-22;q23). The core binding factor leukemias with the translocations t(8;21)(q22;q22) and inv(16)(p13q22) occurred at incidences of 14% and 7%, respectively, predominantly in older children, and their prognosis was favorable. An adverse outcome was observed in patients with monosomy 7, abnormalities of 5q, and t(6;9)(p23;q34). Abnormalities of 3q and complex karyotypes, in the absence of favorable-risk features, have been associated with an adverse outcome in adults, but the results were not significant in this childhood series. However, the presence of 12p abnormalities predicted a poor outcome.

Conclusion

Because the spectrum of chromosomal changes and their risk association seem to differ between children and adults with AML, biologic differences are emerging, which will contribute to the redefinition of risk stratification for different age groups in the future.
Counteracting Counterfeiting? Bodin, Mariana, and Locke on False Money as a Multidimensional Issue
Authors: Desmedt Ludovic , Blanc Jérôme
Published: May 2010

Far more than the problem of the quantity of money, false money was the central issue in monetary debates that occurred in Europe in the sixteenth and seventeenth centuries. It first referred to sovereignty, in a time of state-building, as well as to a serious economic problem. Beyond sovereignty and economy, justice and the public faith were endangered by those who falsified the currency. Yet, the thesis of this paper is that one cannot understand false money in the early modern period by reading texts of that time with today's understanding of false money in mind. The variety of falsifications and their interconnections appear especially when carefully reading the monetary discourses of Jean Bodin, Juan de Mariana, and John Locke. These authors developed arguments about the limits of political powers in the context of currency management. A general claim to counteract counterfeiting (as implemented by individuals) may conceal a claim to suppress any possibility of debasing, and even enhancing, currency (as decided by princes). Clarifying the monetary discourses on the topic and establishing a hierarchy between those dimensions help us understand why the false-money issue was first considered a matter of monetary justice by the prince himself. We identify the multiple dimensions of false money: counterfeiting, degradation of coins, debasement, and enhancement. Until the end of the seventeenth century, monetary instability impeded the development of production in the long run. Stabilizations, through a monetary revolution close to what had been proposed by Bodin, Mariana, and Locke, occurred between the end of the seventeenth and the beginning of the eighteenth century.
Fabrication of a polyaniline/CdSe nanocomposite film light-emitting device by the chemical route
Authors: Sharma S K , Sharma A B , Sharma M , Reddy D Sreekantha , Pandey R K
Published: May 2010

PANI/CdSe multiple-quantum wells (MQWs) and high-brightness MQW light-emitting diodes were grown by the chemical technique. An aniline monomer was electropolymerized to polyaniline (PANI) by using camphor sulphonic acid (CSA). Electrodeposited PANI, chemically synthesized cadmium selenide quantum dots (Q-CdSe), and nanocomposite films (PANI/Q-CdSe) were investigated in optical, structural, and morphological studies. A crystallite size of approximately 1.9nm was calculated from the (111) diffraction peak of Q-CdSe using Scherrer's formula. Multiple peaks in photoluminescence (PL) of PANI/CdSe MQWs and in electroluminescence (EL) of MQW light-emitting devices (LEDs) were observed at room temperature. High-brightness LEDs emitting at 480nm were successfully fabricated with an output power well above 0.2mW at 10mA and with a forward voltage of less than 0.85V.
Resource Utilization and Total Cost of Commercially-Available versus Manually-Compounded Solutions Used for Dialysate in Continuous Renal Replacement Therapy
Authors: Barletta Jeffrey F. , McAllen Karen J. , Hage Michael J. , Steele Brian , Bunchman Timothy E. , Barletta Gina-Marie
Published: May 2010

Purpose

The acquisition cost of commercially-available (CA) dialysis solutions is higher than manually-compounded (MC) solutions but pharmacy preparation time and medication errors are presumed to be lower. The objective of this study was to compare resource utilization and total cost between CA- and MC-dialysis solutions.

Methods

A model was constructed using solution acquisition cost, preparation cost, and the cost of a medication error. Solution preparation costs were obtained by prospectively recording preparation times for 1 month before and after the implementation of a CA-solution protocol. Preparation times were converted to costs using the hourly wage of a pharmacist and pharmacy technician. The presumed error rate was 0.5% for MC and 0.1% for CA solutions. A univariate sensitivity analysis was conducted by varying the incidence of a medication error.

Results

Preparation time for an MC solution was significantly longer than for a CA solution (8 ± 3 minutes/bag vs 4 ± 1 minutes/bag, P < .001). Total solution costs (acquisition + preparation) were $11.13 and $26.38 per bag for MC and CA, respectively. When medication errors were considered, the cost per error-free event was $48.14 per bag for MC solutions and $33.77 per bag for CA solutions. The threshold where the cost-ratio became less costly for MC solutions was when the absolute difference in error rate was no more than 0.2%.

Conclusion

Despite a higher acquisition cost, CA solutions could result in lower total costs compared with MC solutions. A small difference in medication error rate is required to produce these savings.
A Retrospective Medication Use Evaluation of Pioglitazone in Patients with Type 2 Diabetes Mellitus in a County Health Care System
Authors: John Ligy , Milton-Brown Jacqueline , Lal Lincy S.
Published: May 2010

Background

Pioglitazone is a thiazolidinedione oral second-line antihyperglycemic agent in the treatment of type 2 diabetes but was the highest expenditure within restricted drugs in this county health care system. Objective: A medication use evaluation of pioglitazone was conducted to determine if usage was according to guideline as well as evaluate intermediate clinical outcomes.

Methods

This is a retrospective analysis of a convenience sample of 199 patients who were prescribed pioglitazone therapy over a 6-month period. The following data were collected: demographics, indication, dosing, concurrent diabetes medications, pre- and post-glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), liver function tests, lipid profiles, and adverse drug events. Data were analyzed by descriptive statistics, t-test, and chi-square test.

Results

The final analysis included 199 patients of which 194 (97%) had documented prespecified guideline criterion for pioglitazone use. The average patient's age was 55 (standard deviation [SD] 9.5), and 72 (36.2%) of the patients were male. Ninety-nine percent of the patients were on dual therapy. After an average follow-up period of 10.5 weeks, the HbA1c decreased from a mean of 9.8% (SD 1.8%) to 8.7% (SD 1.7%) ( P < 0.05) and FBG decreased from a mean of 212 mg/dL (SD 72 mg/dL) to 174 mg/dL (SD 74 mg/dL) ( P < 0.05). In a subanalysis of 98 patients with pre- and post-lipid panels, the high-density lipoprotein (HDL) increased ( P < 0.001) and triglycerides decreased ( P < 0.02).

Conclusion

Pioglitazone usage in this county health care system meets preset criteria 97.5% of the time and contributes to improved glycemic control. As to whether the impact on surrogate markers led to decreases in morbidity and mortality needs to be researched in larger prospective studies in the county population.
Dexrazoxane
Authors: Cada Dennis J. , Levien Terri , Baker Danial E.
Published: May 2010

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to your Pharmacy & Therapeutics Committee. Subscribers also receive monthly 1-page summary monographs on the agents that are useful for agendas and pharmacy/nursing inservices. A comprehensive target drug utilization evaluation (DUE) is also provided each month. With a subscription, the monographs are sent to you in print and CD-ROM forms and are also available online. Monographs can be customized to meet the needs of your facility. Subscribers to the The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X.

Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. If you would like information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800-322-4349. The January 2008 monograph topics are sevelamer carbonate, diclofenac sodium topical gel, rilonacept, bazedoxifene acetate, and clevidipine butyrate injectable emulsion. The DUE is on sevelamer carbonate.
Pimecrolimus: Lichen Planus (Oral)
Authors: Generali Joyce , Cada Dennis J.
Published: May 2010

Off-Label Drug Uses— This Hospital Pharmacy feature is extracted from Off-Label DrugFacts, a quarterly publication available from Wolters Kluwer Health. Off-Label DrugFacts is a practitioner-oriented resource for information about specific FDA-unapproved drug uses. This new guide to the literature will enable the health care professional/clinician to quickly identify published studies on off-label uses and to determine if a specific use is rational in a patient care scenario. The most relevant data are provided in tabular form, so the reader can easily identify the scope of information available. A summary of these data—including background, study design, patient population, dosage information, therapy duration, results, safety, and therapeutic considerations—precedes each table of published studies. References direct the reader to the full literature for more comprehensive information prior to patient care decisions. Direct questions or comments regarding “Off-Label Drug Uses” to hospitalpharmacy@wolterskluwer.com .
Bariatric Surgery: Impact on Medication Management
Authors: Sardo Pam , Walker Jodi H.
Published: May 2010

Purpose

Bariatric surgery requires permanent changes in the approach to administration of pharmaceuticals, lifestyle, and medical care.

Bariatric surgery is currently recommended only for adolescents and adults who are severely overweight and have comorbid conditions. Often, obesity-related health problems improve or disappear after the weight is lost. As a life changing event, bariatric surgery requires permanent changes in the approach to health care. Postsurgical selection of medication will be quite different from therapeutic regimen options prior to surgery. In addition, bariatric surgery has resulted in reduction of medication intake associated with obesity-related comorbid disease. Patients will require detailed education to ensure awareness regarding medication-related precautions.

Conclusion

Options described in this article will assist the health care team to individually tailor medications to meet the needs of the unique post-bariatric surgery patient population.
Raltegravir Potassium
Authors: Cada Dennis J. , Levien Terri , Baker Danial E.
Published: May 2010

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to your Pharmacy & Therapeutics Committee. Subscribers also receive monthly 1-page summary monographs on the agents that are useful for agendas and pharmacy/nursing inservices. A comprehensive target drug utilization evaluation (DUE) is also provided each month. With a subscription, the monographs are sent to you in print and are also available online. Monographs can be customized to meet the needs of your facility. Subscribers to the The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X.

Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. If you would like information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800-322-4349. The February 2008 monograph topics are nilotinib, sapropterin dihydrochloride, asenapine, bendamustine hydrochloride, and lacosamide. The DUE is on oral therapy for pulmonary hypertension.
Advanced Practice Programs in Hospital Pharmacy –Investigational Drug Services
Authors: Mark Scott M. , Weber Robert J.
Published: May 2010

The Director's Forum series is written and edited by Michael Sanborn and Robert Weber and is designed to guide pharmacy leaders in establishing patient-centered services in hospitals and health systems. Another specific goal of this column is to address many of the key challenges that pharmacy directors face today, while providing information to foster growth in pharmacy leadership and patient safety. This month's Forum focuses on developing a pharmacy-based investigational drug service in a hospital pharmacy department. As part of a patient-centered pharmacy department, a investigational drug service can significantly contribute to the research mission of a hospital.
Amoxicillin-Associated Hemorrhagic Colitis; Sertraline-Induced Paresthesia; Perioral Dermatitis Associated with an Inhaled Corticosteroid; Aminoglycoside-Induced Hepatotoxicity; Flagellate Dermatitis Seen with Bleomycin; Persistent Hiccups with Intrathecal Morphine Therapy; Sibutramine-Induced Psychosis
Authors: Shuster Joel
Published: May 2010

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the Food and Drug Administration's (FDA) medWatch program (800-FDA-1088). If you have reported an interesting preventable ADR to medWatch, please consider sharing the account with our readers.
Recombinant Factor VIIa for Intracerebral Hemorrhage
Authors: Bandali Farooq A. , Thomas Zachariah
Published: May 2010

This feature examines the impact of pharmacologic interventions on the treatment of the critically ill patient — an area of health care that has become increasingly complex. Recent advances in drug therapy (including evolving and controversial data) for adult intensive care unit patients will be reviewed and assessed in terms of clinical, humanistic, and economic outcomes. Direct questions or comments to Zachariah Thomas, PharmD at zachariah.thomas@gmail.com or Sandra Kane-Gill, PharmD, MSc, at kanesl@upmc.edu .
Ixabepilone; Nilotinib
Authors: Solimando Dominic A. , Waddell J. Aubrey
Published: May 2010

The increasing complexity of cancer chemotherapy now requires that pharmacists be familiar with these highly toxic agents. This column will review various issues related to preparation, dispensing, and administration of cancer chemotherapy, and review various agents, both commercially available and investigational, used to treat malignant diseases.
One Tablet or One Bottle? Avoiding Mix-Ups between Sterile Water and Sodium Chloride Bags a Chain is Only as Strong as its Weakest Link
Authors: Cohen Michael R. , Smetzer Judy L.
Published: May 2010

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them in your inservice training programs.

Your assistance is required to continue this feature. The reports described here were received through the USP Medication Errors Reporting Program (MERP), which is presented in cooperation with the Institute for Safe Medication Practices (ISMP). If you have encountered medication errors and would like to report them, you may call USP toll-free, 24 hours a day, at 800-233-7767 (800-23-ERROR).

Any reports published by ISMP will be anonymous. Comments are also invited; the writers' names will be published if desired. ISMP may be contacted at the address shown below.

Errors, close calls, or hazardous conditions may be reported through the ISMP ( www.ismp.org ) or United States Pharmacopeia (USP) ( www.usp.org ) Web sites or communicated directly to ISMP by calling 800-FAIL-SAFE or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters' wishes as to the level of detail included in publications.
Omega-3 Fatty Acids: Emerging Role for Cardioprotection
Authors: Backes James M. , Howard Patricia A.
Published: May 2010

This continuing feature will update readers on recent developments in cardiovascular pharmacotherapy. Cardiovascular disease remains the number one killer in the United States and more clinical outcome trials have been conducted in cardiology than in any other field of medicine. Given this rapidly expanding knowledge base, pharmacists can have a significant impact on prevention and treatment—if they keep current with developments in drug therapy.
Gemcitabine and Docetaxel (GD) for Advanced Soft Tissue Sarcomas
Authors: Whitmore M. Brooke , Worley Katherine B. , Waddell J. Aubrey , Solimando Dominic A.
Published: May 2010

The increasing complexity of cancer chemotherapy now requires that pharmacists be familiar with these highly toxic agents. This column will review various issues related to preparation, dispensing, and administration of cancer chemotherapy, and review various agents, both commercially available and investigational, used to treat malignant diseases.
Doripenem for Injection
Authors: Cada Dennis J. , Levien Terri , Mistry Bhavin , Baker Danial E.
Published: May 2010

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to your Pharmacy & Therapeutics Committee. Subscribers also receive monthly 1-page summary monographs on the agents that are useful for agendas and pharmacy/nursing inservices. A comprehensive target drug utilization evaluation (DUE) is also provided each month. With a subscription, the monographs are sent to you in print and are also available online. Monographs can be customized to meet the needs of your facility. Subscribers to the The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X.

Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. If you would like information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800-322-4349. The March 2008 monograph topics are nebivolol, 6% hydroxyethyl starch 130/0.4 in 0.9% normal saline, romiplostim, tocilizumab, and prasugrel. The DUE is on nebivolol.
Pharmacists, Get Connected: Cellular Broadband for Smartphones
Authors: Fox Brent I. , Felkey Bill G.
Published: May 2010

Over the course of its evolution, the personal digital assistant (PDA) has grown from a predominantly offline, referential tool that had to be synchronized to a personal computer for updates to one that is integrated with a cell phone and subsequently yields high-speed global connectivity. This integration provides pharmacists with mobile access to virtually any available information from anywhere. Early uses of smartphones for Internet access were often frustrating due to slow speeds and poor reliability. The end user's experience with cellular broadband has changed dramatically over the last few years. What follows is an exploration of the technology and capabilities underlying PDA and smartphone connectivity.
Working Effectively with Consultants
Authors: Sanborn Michael
Published: May 2010

The Director's Forum series is written and edited by Michael Sanborn and Robert Weber and is designed to guide pharmacy leaders in establishing patient-centered services in hospitals and health systems. Another specific goal of this column is to address many of the key challenges that pharmacy directors currently face, while providing information to foster growth in pharmacy leadership and patient safety. This Director's Forum article focuses on the use of consultants in pharmacies and in health care. This is a unique topic that most directors will address at one time or another during their careers.
Persistence Saves Patient's Life; Do Not Use Epidural Tubing for an Intravenous Solution; Topical Antiseptic Given Orally; Refrigerator Monitoring
Authors: Cohen Michael R.
Published: May 2010

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them in your inservice training programs.

Your assistance is required to continue this feature. The reports described here were received through the USP Medication Errors Reporting Program (MERP), which is presented in cooperation with the Institute for Safe Medication Practices (ISMP). If you have encountered medication errors and would like to report them, you may call USP toll-free, 24 hours a day, at 800-233-7767 (800-23-ERROR).

Any reports published by ISMP will be anonymous. Comments are also invited; the writers' names will be published if desired. ISMP may be contacted at the address shown below.

Errors, close calls, or hazardous conditions may be reported through the ISMP ( www.ismp.org ) or United States Pharmacopeia (USP) ( www.usp.org ) Web sites or communicated directly to ISMP by calling 800-FAIL-SAFE or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters' wishes as to the level of detail included in publications.
Drug-Induced Aseptic Meningitis with Amoxicillin; Restless Legs Syndrome Associated with Escitalopram; Toxic Epidermal Necrolysis with Fluoxetine; Serotonin Syndrome Precipitated by Amantadine Therapy and Renal Failure; Sunitinib and Allergic Interstitial Nephritis; Two Separate Reports of Adverse Drug Reactions with Duloxetine
Authors: Shuster Joel
Published: May 2010

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the Food and Drug Administration's (FDA) MEDWATCH program (800-FDA-1088). If you have reported an interesting preventable ADR to MEDWATCH, please consider sharing the account with our readers.
Autoimmune-Hemolytic Anemia Associated with Montelukast and Zafirlukast Therapy in a Patient with Hepatitis C
Authors: Wargo Kurt A. , Roark Kimberly , Ibrahim Farrah
Published: May 2010

Objective

To report a case of autoimmune-hemolytic anemia (AIHA) associated with montelukast and, subsequently, zafirlukast in a patient with hepatitis C.

Case Summary

A 57-year-old white man with known hepatitis C presented with jaundice, bilateral lower-extremity edema, fatigue, and exertion for 3 weeks. He started using montelukast a week prior to experiencing these symptoms. After consultation with his primary care provider, montelukast was replaced with zafirlukast, which improved edema but other symptoms persisted. The patient was admitted to the hospital with symptoms, physical findings, and laboratory tests suggestive of AIHA. Leukotriene receptor antagonist therapy was discontinued and the patient received treatment with red blood cell transfusions and corticosteroids. The patient's hemoglobin stabilized within 9 days.

Discussion

AIHA may occur idiopathically or secondarily in association with drug or chemical exposures, lymphoproliferative disorders, collagen vascular diseases, or malignancies. Several mechanisms for drug-induced AIHA have been elucidated; however, direct laboratory testing is difficult. Therefore, diagnosis of drug-induced AIHA should be made when other causes have been ruled out, when temporal relation can be made, and when improvement of symptoms occurs upon discontinuation of the suspected agent.

Conclusion

Over 100 drugs have been implicated in the formation of warm antibody hemolytic anemia; however, there are currently no reports of leukotriene receptor antagonists associated with AIHA. Even though, in this case report, the patient had coexisting hepatitis C, which can cause AIHA alone, an objective causality assessment revealed that the AIHA was possibly due to montelukast and zafirlukast.
PDAs and Smartphones: Are you Practicing Safe Mobile Computing?
Authors: Felkey Bill G. , Fox Brent I.
Published: May 2010

Portable information appliances have become ubiquitous in pharmacy practice. The value of virtually anytime-anywhere information access is arguably the most important feature of these devices. However, this ability is also one of the most significant threats of using these devices. Portable information access poses certain security risks that we were not presented with prior to the adoption of these devices. This installment addresses mobile computing and how to increase the security of your personal digital assistant/smartphone use.