bluuebunny/crossref_metadata_2025 huggingface dataset:
A Genetic Locus Accentuates the Effect of Volume Overload on Adverse Left Ventricular Remodeling in Male and Female Rats
Authors: Souzeau Emmanuelle , Llamas Bastien , Bélanger Sonia , Picard Sylvie , Deschepper Christian F.
Published: December 2005

Although increased left ventricular (LV) mass is highly predictive of cardiovascular morbidity and mortality in humans, it has never been verified in an experimental model that naturally occurring alleles linked to increased LV mass under basal conditions also associate with worsened cardiovascular prognosis. Because we have shown previously that locus
Cm24
on chromosome 5 was responsible for differences in LV mass between WKY and WKHA rats, we used WKY.WKHA-(
D5Rat45-D5Rat245
) congenic rats (where locus
Cm24
has been transferred from WKHA into WKY rats) to test how naturally occurring gene variants present in
Cm24
would, in addition to their effects under basal conditions, affect LV mass remodeling and/or function in the context of overload. Volume overload was induced in WKY, WKHA, and WKY.WKHA congenic rats by surgical creation of an aorto-caval fistula. In females, the fistula had no effect on the hearts of WKY rats, yet it induced dilated eccentric hypertrophy and isolated diastolic dysfunction in WKHA and WKY.WKHA congenic rats, along with signs of congestive heart failure. In males, the surgical maneuver induced only mild or inconsistent responses in WKY rats but had much more pronounced effects in WKHA and WKY.WKHA congenic rats. Altogether, our data show that a genetic locus that induces, under basal conditions, either mild or no concentric LV remodeling in either male or female rats, respectively, associates with LV dilatation and dysfunction in both sexes when the hearts are additionally challenged.
Tetrahydrobiopterin, but Not
l
-Arginine, Decreases NO Synthase Uncoupling in Cells Expressing High Levels of Endothelial NO Synthase
Authors: Bevers Lonneke M. , Braam Branko , Post Jan Andries , van Zonneveld Anton Jan , Rabelink Ton J. , Koomans Hein A. , Verhaar Marianne C. , Joles Jaap A.
Published: December 2005

Endothelial NO synthase (eNOS) produces superoxide when depleted of (
6R
)-5,6,7,8-tetrahydro-
l
-biopterin (BH
4
) and
l
-arginine by uncoupling the electron flow from NO production. High expression of eNOS has been reported to have beneficial effects in atherosclerotic arteries after relatively short periods of time. However, sustained high expression of eNOS may have disadvantageous vascular effects because of uncoupling. We investigated NO and reactive oxygen species (ROS) production in a microvascular endothelial cell line (bEnd.3) with sustained high eNOS expression and absent inducible NOS and neuronal NOS expression using 4,5-diaminofluorescein diacetate and diacetyldichlorofluorescein as probes, respectively. Unstimulated cells produced both NO and ROS. After stimulation with vascular endothelial growth factor (VEGF), NO and ROS production increased. VEGF-induced ROS production was even further increased by the addition of extra
l
-arginine. N
ω
-nitro-
l
-arginine methyl ester decreased ROS production. These findings strongly suggest that eNOS is a source of ROS in these cells. Although BH
4
levels were increased as compared with another endothelial cell line, eNOS levels were >2 orders of magnitude higher. The addition of BH
4
resulted in increased NO production and decreased generation of ROS, indicating that bEnd.3 cells produce ROS through eNOS uncoupling because of relative BH
4
deficiency. Nevertheless, eNOS-dependent ROS production was not completely abolished by the addition of BH
4
, suggesting intrinsic superoxide production by eNOS. This study indicates that potentially beneficial sustained increases in eNOS expression and activity could lead to eNOS uncoupling and superoxide production as a consequence. Therefore, sustained increases of eNOS or VEGF activity should be accompanied by concomitant supplementation of BH
4
.
Low Muscular Mass and Overestimation of Microalbuminuria by Urinary Albumin/Creatinine Ratio
Authors: Cirillo Massimo , Laurenzi Martino , Mancini Mario , Zanchetti Alberto , De Santo Natale G.
Published: December 2005

Microalbuminuria is a mild urinary albumin elevation and is associated with cardiovascular disease. Urinary albumin/creatinine ratio is recommended for microalbuminuria assessment, because it reflects urinary albumin excretion. Muscular mass could affect albumin/creatinine ratio, because urinary creatinine reflects muscular mass. The study investigated high albumin/creatinine ratio attributed to low urinary creatinine without microalbuminuria. The Gubbio Population Study for ages 45 to 64 collected data on weight, skinfold, urinary albumin, urinary creatinine, and coronary heart disease. Weight and skinfold thickness were used to calculate fat and nonfat mass and urinary creatinine as a marker of muscular mass. Microalbuminuria was defined as urinary albumin of 20 to 199 μg/min and high albumin/creatinine ratio as a ratio of 17 to 250 μg/mg in men and of 25 to 355 μg/mg in women. Persons with macroalbuminuria (urinary albumin ≥200 μg/min) were excluded to focus analyses on microalbuminuria. Coronary heart disease was defined by ECG and questionnaire. The target cohort consisted of 1623 men and women, ages 45 to 64. Prevalence was 8.5% for high albumin/creatinine ratio (n=138), 4.3% for microalbuminuria (n=69), 5.2% for high albumin/creatinine ratio without microalbuminuria (n=85), and 1.0% for nonhigh albumin/creatinine ratio with microalbuminuria (n=16). High albumin/creatinine ratio without microalbuminuria was inversely associated with nonfat mass and urinary creatinine (
P
<0.04). Compared with persons with a nonhigh albumin/creatinine ratio, coronary heart disease was more prevalent in persons with a high albumin/creatinine ratio and microalbuminuria (18.9% and 7.1%;
P
=0.002), not in persons with a high albumin/creatinine ratio without microalbuminuria (8.2% and 7.1%;
P
=0.706). A high albumin/creatinine ratio in persons with low muscle mass indicates low urinary creatinine more often than microalbuminuria and cardiovascular disease.
Views on the Ground: The Local Perception of International Criminal Tribunals in the Former Yugoslavia and Sierra Leone
Authors: Arzt Donna E.
Published: December 2005

If international criminal courts are to achieve their aims—one of which is to contribute to the consolidation of democracy and the triumph of the rule of law over the instinct for revenge after prolonged periods of communal violence—perception of their legitimacy by the local population is a crucial factor. After laying out and comparing the basic features of the International Criminal Tribunal for the former Yugoslavia and the Special Court for Sierra Leone as to their respective origins, objectives, and programs of outreach, the article examines local reception from three standpoints: perceptions of overall legitimacy, perceptions of tribunal impartiality, and the effect of public perceptions of the tribunals on the respective countries' reconciliation process.
Law and Development of Constitutional Democracy: Is China a Problem Case?
Authors: Peerenboom Randall
Published: December 2005

China is frequently portrayed as a problem case for the law and development movement because it has achieved economic growth with a weak legal system, has resisted the third wave of democratization, and has a poor record on civil and political rights. Is China a problem case? The author thinks not, or at least that it is too early to tell. China is now following the path of other East Asian countries that have achieved sustained economic growth, established rule of law, and developed constitutional or rights-based democracies, albeit not necessarily liberal rights-based democracies. At this stage of development, for all of its problems, China is meeting or exceeding expectations on most measures. China outperforms the average country in its income class in terms of economic growth, rule of law and most human rights measures, and other indicators of human well-being with the notable exception of civil and political rights.
Global Rule of Law or Global Rule of Law Enforcement? International Police Cooperation and Counterterrorism
Authors: Deflem Mathieu
Published: December 2005

With increasing vigor since the events of September 11, 2001, police institutions across the globe have proliferated their counterterrorism strategies, including participation in international police organizations such as the International Criminal Police Organization (Interpol). This article discusses some of these developments in light of the prospects of the development toward a global rule of law. Based on the theory of police bureaucratization, it is shown that police institutions have independently developed international structures and practices irrespective of international accords. This article reveals the dynamics of such international police efforts by examining the counterterrorist policies of Interpol. It is argued that the outcome of the relative separation between international police practices, on one hand, and global legal developments, on the other, will be critical in assessing any efforts to counteract the societal processes and conditions that may facilitate the development of terrorism on a global scale.
The “Good Governance” Concept Revisited
Authors: Nanda Ved P.
Published: December 2005

The term “good governance” is unsettled in its meaning. Through the 1980s and 1990s, donor countries and institutions trended to make aid conditional upon reforms in the recipient country, which was found largely ineffective in encouraging real policy changes. More recently, donors, such as the International Monetary Fund, the World Bank, and the United States, are increasingly insisting upon performance and good governance as a prerequisite for aid, a practice called “selectivity.” This is a means of requiring a recipient state to demonstrate the seriousness of its commitment to economic and social reforms. There are no objective standards for determining good governance: some aspects include political stability, the rule of law, control of corruption, and accountability. High levels of poverty and weak governance are linked, making selectivity difficult to implement. For reforms to succeed, domestic support, ownership, and commitment are crucial, as are the recipient's cultural context and history.
Can the Welfare State Survive in a Globalized Legal Order?
Authors: Krislov Samuel
Published: December 2005

The notion that markets lead to law and freedom is said to have originated in Adam Smith's work and is rooted in history. Both the progression and roots seem highly problematic. Neo-Smithian approaches have been refurbished by general acceptance of a contingent nature of the relation. They have also been enhanced by the failures of European Marxist economics in ways predicted with uncanny accuracy. On the other hand, neoclassical claims that democratic welfare systems were only a step away from similar failures have been refuted. Hopes that an international system might impose democracy from outside the nation-state are overly optimistic. Nationalism is rife, with a continuing outburst of ethnic secessions, and little yielding of power to supranational decision makers. The greatest success of supranational authority has rather been in creating subsidiary structures, unlikely to implement fundamental transformation but with potential for supporting such a thrust. These include expert-based operations and the network of nongovernmental organizations.
Combat Exposure, Perceived Benefits of Military Service, and Wisdom in Later Life
Authors: Jennings Patricia A. , Aldwin Carolyn M. , Levenson Michael R. , Spiro Avron , Mroczek Daniel K.
Published: December 2005

Stress, even extremely traumatic stress, may pose both risks and benefits. Although combat can have lifelong negative consequences, the perception of positive benefits from military experience can mitigate the negative effects of combat on mental health. However, little research has examined the impact of trauma earlier in life on the development of positive adaptation, such as wisdom, later in life. The authors examined whether combat exposure and the perception of benefits from military experience, assessed in 1990, were associated with greater wisdom in later life, assessed in 2001 in 615 men from the Normative Aging Study men (mean age 74 years, SD = 6.8 years). A quadrilinear relationship between combat exposure and wisdom was found. Moderate levels of combat were associated with higher levels of wisdom. The perception of benefits and coping predicted wisdom. Thus, how one appraises and copes with problems may be more important in the prediction of positive adaptation than the simple occurrence of stress.
Watchdog or Good Neighbor?
Authors: Poindexter Paula M. , Heider Don , McCombs Maxwell
Published: December 2005

After an earlier study found the public’s dominant expectation of the press was to be a good neighbor and not a watchdog, the present study set out to determine what being a good neighbor meant for different segments of the public. The analysis revealed that being a good neighbor was strongly valued by women, African Americans, and Hispanics. Many in these groups wanted more coverage of education, health and medicine, science, and arts and culture. The segment of the public that expected the press to be a good neighbor was concerned about crime and social issues, and television was viewed as best able to address these concerns. This study fills a void in the empirical public journalism literature that has primarily focused on journalists’ opinions, the content of public journalism projects, and the impact of public journalism projects on the public. Unlike most of the previous literature, which has ignored the public’s opinions about journalistic practices associated with public journalism, the present study connects the public’s expectations of local news as a good neighbor with techniques that epitomize public journalism, that is, caring about the community, reporting on interesting people and groups, understanding the local community, and offering solutions.
ATRA resolves the differentiation block in t(15;17) acute myeloid leukemia by restoring PU.1 expression
Authors: Mueller Beatrice U. , Pabst Thomas , Fos José , Petkovic Vibor , Fey Martin F. , Asou Norio , Buergi Ulrich , Tenen Daniel G.
Published: December 2005

Tightly regulated expression of the transcription factor PU.1 is crucial for normal hematopoiesis. PU.1 knockdown mice develop acute myeloid leukemia (AML), and PU.1 mutations have been observed in some populations of patients with AML. Here we found that conditional expression of promyelocytic leukemia-retinoic acid receptor α (PML-RARA), the protein encoded by the t(15;17) translocation found in acute promyelocytic leukemia (APL), suppressed PU.1 expression, while treatment of APL cell lines and primary cells with all-trans retinoic acid (ATRA) restored PU.1 expression and induced neutrophil differentiation. ATRA-induced activation was mediated by a region in the PU.1 promoter to which CEBPB and OCT-1 binding were induced. Finally, conditional expression of PU.1 in human APL cells was sufficient to trigger neutrophil differentiation, whereas reduction of PU.1 by small interfering RNA (siRNA) blocked ATRA-induced neutrophil differentiation. This is the first report to show that PU.1 is suppressed in acute promyelocytic leukemia, and that ATRA restores PU.1 expression in cells harboring t(15;17).
Comparative genome analysis reveals a conserved family of actin-like proteins in apicomplexan parasites
Authors: Gordon Jennifer L , Sibley L David
Published: December 2005

Background

The phylum Apicomplexa is an early-branching eukaryotic lineage that contains a number of important human and animal pathogens. Their complex life cycles and unique cytoskeletal features distinguish them from other model eukaryotes. Apicomplexans rely on actin-based motility for cell invasion, yet the regulation of this system remains largely unknown. Consequently, we focused our efforts on identifying actin-related proteins in the recently completed genomes of Toxoplasma gondii, Plasmodium spp., Cryptosporidium spp., and Theileria spp.

Results

Comparative genomic and phylogenetic studies of apicomplexan genomes reveals that most contain only a single conventional actin and yet they each have 8–10 additional actin-related proteins. Among these are a highly conserved Arp1 protein (likely part of a conserved dynactin complex), and Arp4 and Arp6 homologues (subunits of the chromatin-remodeling machinery). In contrast, apicomplexans lack canonical Arp2 or Arp3 proteins, suggesting they lost the Arp2/3 actin polymerization complex on their evolutionary path towards intracellular parasitism. Seven of these actin-like proteins (ALPs) are novel to apicomplexans. They show no phylogenetic associations to the known Arp groups and likely serve functions specific to this important group of intracellular parasites.

Conclusion

The large diversity of actin-like proteins in apicomplexans suggests that the actin protein family has diverged to fulfill various roles in the unique biology of intracellular parasites. Conserved Arps likely participate in vesicular transport and gene expression, while apicomplexan-specific ALPs may control unique biological traits such as actin-based gliding motility.
Diagnostic and treatment delay among pulmonary tuberculosis patients in Ethiopia: a cross sectional study
Authors: Yimer Solomon , Bjune Gunnar , Alene Getu
Published: December 2005

Background

Delayed diagnosis and treatment of tuberculosis (TB) results in severe disease and a higher mortality. It also leads to an increased period of infectivity in the community. The objective of this study was to determine the length of delays, and analyze the factors affecting the delay from onset of symptoms of pulmonary tuberculosis (PTB) until the commencement of treatment.

Methods

In randomly selected TB management units (TBMUs), i.e. government health institutions which have diagnosing and treatment facilities for TB in Amhara Region, we conducted a cross sectional study from September 1-December 31/2003. Delay was analyzed from two perspectives, 1. Period between onset of TB symptoms to first visit to any health provider (health seeking period), and from the first health provider visit to initiation of treatment (health providers' delay), and 2. Period between onset of TB symptoms to first visit to a medical provider (patients' delay), and from this visit to commencement of anti-TB treatment (health systems' delay). Patients were interviewed on the same date of diagnosis using a semi-structured questionnaire. Logistics regression analysis was applied to analyze the risk factors of delays.

Results

A total of 384 new smear positive PTB patients participated in the study. The median total delay was 80 days. The median health-seeking period and health providers' delays were 15 and 61 days, respectively. Conversely, the median patients' and health systems' delays were 30 and 21 days, respectively. Taking medical providers as a reference point, we found that forty eight percent of the subjects delayed for more than one month. Patients' delays were strongly associated with first visit to non-formal health providers and self treatment (P < 0.0001). Prior attendance to a health post/clinic was associated with increased health systems' delay (p < 0.0001).

Conclusion

Delay in the diagnosis and treatment of PTB is unacceptably high in Amhara region. Health providers' and health systems' delays represent the major portion of the total delay. Accessing a simple and rapid diagnostic test for TB at the lowest level of health care facility and encouraging a dialogue among all health providers are imperative interventions.
High-resolution genotyping of Pseudomonas aeruginosa strains linked to acute post cataract surgery endophthalmitis outbreaks in India
Authors: Kenchappa Prashanth , Sangwan Virender S , Ahmed Niyaz , Rao K Rajender , Pathengay Avinash , Mathai Annie , Mansoori Tarannum , Das Taraprasad , Hasnain Seyed E , Sharma Savitri
Published: December 2005

Background

Investigation of two independent outbreaks of post cataract surgery endophthalmitis identified the reservoir of epidemic strains of P. aeruginosa.

Methods

Patient isolates cultured from vitreous fluid of all the nine cases and from the peripheral devices of phacoemulsification machine were subjected to high-resolution Fluorescent Amplified Fragment Length Polymorphism (FAFLP) analysis.

Results

FAFLP based genotyping of the isolates confirmed nosocomial transmission. Although biochemical characterization and antibiotic susceptibility profiles grouped all the isolates together, FAFLP based genotyping revealed that, all the outbreak isolates were derived from 2 different strains, with independent origins. One group of isolates was traced to phacoprobe and the second one to the internal tubing system of the phacoemulsification machine used in cataract surgery. In silico analysis indicated possible evolution in both the clusters of P. aeruginosa isolates due to genetic polymorphisms. The polymorphisms were mapped to gene products (cell envelope, outer membrane proteins) possibly having significant role in pathogenesis.

Conclusion

The present study is probably the first one to apply FAFLP typing successfully to investigate outbreaks of postoperative endophthalmitis (POE) in an ophthalmic setting, which was able to identify the source, and helped to make rational decisions on sterilization procedures that halted more cases of infection in these hospitals.
Repolarization of the action potential enabled by Na+ channel deactivation in PSpice simulation of cardiac muscle propagation
Authors: Ramasamy Lakshminarayanan , Sperelakis Nicholas
Published: December 2005

Background

In previous studies on propagation of simulated action potentials (APs) in cardiac muscle using PSpice modeling, we reported that a second black-box (BB) could not be inserted into the K+ leg of the basic membrane unit because that caused the PSpice program to become very unstable. Therefore, only the rising phase of the APs could be simulated. This restriction was acceptable since only the mechanism of transmission of excitation from one cell to the next was being investigated.

Methods and results

We have now been able to repolarize the AP by inserting a second BB into the Na+ leg of the basic units. This second BB effectively mimicked deactivation of the Na+ channel conductance. This produced repolarization of the AP, not by activation of K+ conductance, but by deactivation of the Na+ conductance. The propagation of complete APs was studied in a chain (strand) of 10 cardiac muscle cells, in which various numbers of gap-junction (gj) channels (assumed to be 100 pS each) were inserted across the cell junctions. The shunt resistance across the junctions produced by the gj-channels (Rgj) was varied from 100,000 M? (0 gj-channels) to 10,000 M? (1 gj-channel), to 1,000 M? (10 channels), to 100 M? (100 channels), and 10 M? (1000 channels). The velocity of propagation (θ, in cm/s) was calculated from the measured total propagation time (TPT, the time difference between when the AP rising phase of the first cell and the last cell crossed -20 mV, assuming a cell length of 150 μm. When there were no gj-channels, or only a few, the transmission of excitation between cells was produced by the electric field (EF), i.e. the negative junctional cleft potential, that is generated in the narrow junctional clefts (e.g. 100 A) when the prejunctional membrane fires an AP. When there were many gj-channels (e.g. 1000 or 10,000), the transmission of excitation was produced by local-circuit current flow from one cell to the next through the gj-channels.

Conclusion

We have now been able to simulate complete APs in cardiac muscle cells that could propagate along a single chain of 10 cells, even when there were no gj-channels between the cells.
Impact of standalone and embedded telephone triage systems on after hours primary medical care service utilisation and mix in Australia
Authors: Dunt David , Day Susan E , Kelaher Margaret , Montalto Michael
Published: December 2005

Background

The Australian government sponsored five local trials aimed at addressing problems in after hours (AH) primary medical care (PMC). The study's objective was to determine if the four trials, where telephone triage was the sole innovation, led to a reduction in AH service utilisation and change in service mix towards AH GP clinics. Changes in utilisation and mix of AH GP clinic and home visits, ED and ambulance use were monitored in the trial areas, and in a national sample to adjust for the effects of secular trend. Pre- and post-trial telephone surveys of two separate random samples of approximately 350 AH PMC user households in each area were conducted.

Results

Some types of AH PMC use became more frequent in both of the standalone services using nurse-administered proprietary call centre software, which were aimed at better addressing population need (Statewide call centre; Regional call centre). Service use overall (95%CI: 1.03–1.83) and GP clinic use (95%CI: 1.07–2.00) increased in the metro area of the Statewide call centre and in GP clinic (95%CI: 1.04–2.14) and home visits (95%CI: 1.03–3.91) in the non-metro area of the Regional call centre. Service mix only changed in the non-metro area of the Regional call centre with increased contact in GP home visits (95%CI: 1.02–4.38). Levels of use remained unchanged in both embedded services using other than proprietary software, which were established to support the GP workforce (Deputising service; Local triage centre). Service mix only changed in the Deputising service with a change away from AH GP clinics in both contact (95%CI: 0.39–0.97) and frequency (95% CI: -2.12 – -0.7).

Conclusion

Bearing in mind limitations in estimating AH PMC utilisation levels and mix, it is concluded that the impacts of telephone triage were generally smaller in Australia than reported elsewhere. There were different impacts on levels of service utilisation and service mix in standalone call centres and embedded services. Impacts of telephone triage on service utilisation and mix are influenced by the type of telephone triage offered, the goals of the agency providing the service, as well as local factors. (345 words)
A health policy for hearing impairment in older Australians: what should it include?
Authors: Smith Jennifer L , Mitchell Paul , Wang Jie Jin , Leeder Stephen R
Published: December 2005

Background

As in all western countries, Australia's older population experiences high levels of hearing impairment coupled with relatively low levels of hearing device usage. Poor hearing diminishes the quality of life of affected individuals and their families. This paper discusses how to improve Australian hearing health policies in order to better combat this impairment amongst older Australians.

Method

We searched the databases Medline, Meditext and Web of Science to find articles that discussed strategies and innovations to assist the hearing health of older people, and related this material to observations made during the Blue Mountains Hearing Study in NSW between 1997 and 2003.

Results and Discussion

The literature search identified five areas for inclusion in a comprehensive hearing health policy in Australia. These are: early intervention; addressing of hearing aid expense; the use of assisted listening devices; hearing rehabilitation, and; screening and education. Further research in Australia is critical if we are to develop a strong approach to the increasing prevalence of age-related hearing loss.

Conclusion

Australia needs to act now to address hearing impairment as it is a major cause of disability in those aged 55 and over. Federal and State governments should collaborate to construct a comprehensive hearing health policy that tackles poor levels of hearing health through early intervention, addressing hearing aid expense, encouraging the use of assisted listening devices, rehabilitation, screening and education. A good start would be to declare age related hearing impairment as a National Health Priority Area.
New MUC1 Serum Immunoassay Differentiates Pancreatic Cancer From Pancreatitis
Authors: Gold David V. , Modrak David E. , Ying Zhiliang , Cardillo Thomas M. , Sharkey Robert M. , Goldenberg David M.
Published: December 2005

Purpose

To evaluate a new immunoassay for identification and quantitation of MUC1 in the sera of patients with pancreatic cancer or pancreatitis. The sensitivity and specificity of the assay are examined and compared to results from a CA19-9 immunoassay.

Methods

An in vitro enzyme immunoassay was established with monoclonal antibody PAM4 as the capture reagent, and a polyclonal anti-MUC1 antibody as the probe. Patient sera were obtained from healthy, adult patients with acute and chronic pancreatitis, and those with pancreatic and other forms of cancer, and were measured for PAM4-reactive MUC1.

Results

At a cutoff of 10.2 units/mL, 41 (77%) of 53 pancreatic cancer patients, none of the healthy individuals (n = 43), and only four (5%) of 87 patients with pancreatitis were positive above this value. Among nonpancreatic cancers investigated, colorectal cancers gave the highest percentage of positives (14%; five of 36). Overall, the sensitivity and specificity of the immunoassay for pancreatic cancer were 77% and 95%, respectively. Receiver operator characteristic analyses for discrimination of pancreatic cancer from pancreatitis provided an area under the curve of 0.89 (95% CI, 0.82 to 0.93), with a specificity of 95.4% and a positive likelihood ratio of 16.8. A direct pair-wise comparison of PAM4 and CA19-9 immunoassays for discrimination of pancreatic cancer and pancreatitis resulted in a significant difference (P < .003), with the PAM4 immunoassay demonstrating superior sensitivity and specificity.

Conclusion

The high sensitivity and specificity observed suggest that the PAM4-based immunoassay of circulating MUC1 may be useful in the diagnosis of pancreatic cancer.
Treatment for Acute Myelogenous Leukemia by Low-Dose, Total-Body, Irradiation-Based Conditioning and Hematopoietic Cell Transplantation From Related and Unrelated Donors
Authors: Hegenbart Ute , Niederwieser Dietger , Sandmaier Brenda M. , Maris Michael B. , Shizuru Judith A. , Greinix Hildegard , Cordonnier Catherine , Rio Bernard , Gratwohl Alois , Lange Thoralf , Al-Ali Haifa , Storer Barry , Maloney David , McSweeney Peter , Chauncey Thomas , Agura Ed , Bruno Benedetto , Maziarz Richard T. , Petersen Finn , Storb Rainer
Published: December 2005

Purpose

The use of low-dose, irradiation-based preparative regimens have allowed the extension of allografting to older and medically infirm patients. The study reported here assessed outcomes for patients with acute myeloid leukemia (AML) in different stages of their disease, who were not considered candidates for conventional hematopoietic cell transplantation (HCT) because of age and/or other known risk factors and were given minimal conditioning followed by HCT from related or unrelated donors.

Patients and Methods

The present study included 122 patients with AML, who were conditioned with 2 Gy total-body irradiation (TBI) on day 0 with or without preceding fludarabine (30 mg/m2/d from days −4 to −2), and given postgrafting cyclosporine at 6.25 mg/kg twice daily from day −3 and mycophenolate mofetil at 15 mg/kg twice daily from day 0.

Results

Durable engraftment was observed in 95% of the patients. Cumulative incidences of acute graft-versus-host disease grades 2 to 4 at 6 months were 35% after related and 42% after unrelated HCT, respectively. With a median follow-up of 44 months (range, 26 to 79 months), 51 patients were alive, of whom 48 were in complete remission (CR). Cumulative nonrelapse mortalities were 10% and 22%, and cumulative mortalities from disease progression were 47% and 33% at 2 years for related and unrelated recipients, respectively. Overall, 2-year survival was 48%, and disease-free survival was 44%. Patients receiving transplantation in CR1 had 2-year overall survivals of 44% after related and 63% after unrelated HCT, respectively.

Conclusion

We conclude that HCT from related and unrelated donors after low-dose TBI is a promising treatment for elderly patients with AML.
High Complete Remission Rate and Promising Outcome by Combination of Imatinib and Chemotherapy for Newly Diagnosed BCR-ABL–Positive Acute Lymphoblastic Leukemia: A Phase II Study by the Japan Adult Leukemia Study Group
Authors: Yanada Masamitsu , Takeuchi Jin , Sugiura Isamu , Akiyama Hideki , Usui Noriko , Yagasaki Fumiharu , Kobayashi Tohru , Ueda Yasunori , Takeuchi Makoto , Miyawaki Shuichi , Maruta Atsuo , Emi Nobuhiko , Miyazaki Yasushi , Ohtake Shigeki , Jinnai Itsuro , Matsuo Keitaro , Naoe Tomoki , Ohno Ryuzo
Published: December 2005

Purpose

A novel therapeutic approach is urgently needed for BCR-ABL–positive acute lymphoblastic leukemia (ALL). In this study, we assessed the efficacy and feasibility of chemotherapy combined with imatinib.

Patients and Methods

A phase II study of imatinib-combined chemotherapy was conducted for newly diagnosed BCR-ABL–positive ALL in adults. Eighty patients were entered into the trial between September 2002 and January 2005.

Results

Remission induction therapy resulted in complete remission (CR) in 77 patients (96.2%), resistant disease in one patient, and early death in two patients, as well as polymerase chain reaction negativity of bone marrow in 71.3%. The profile and incidence of severe toxicity were not different from those associated with our historic chemotherapy-alone regimen. Relapse occurred in 20 patients after median CR duration of 5.2 months. Allogeneic hematopoietic stem-cell transplantation (HSCT) was performed for 49 patients, 39 of whom underwent transplantation during their first CR. The 1-year event-free and overall survival (OS) rates were estimated to be 60.0%, and 76.1%, respectively, which were significantly better than those for our historic controls treated with chemotherapy alone (P < .0001 for both). Among the current trial patients, the probability for OS at 1 year was 73.3% for those who underwent allogeneic HSCT, and 84.8% for those who did not.

Conclusion

Our results demonstrated that imatinib-combined regimen is effective and feasible for newly diagnosed BCR-ABL–positive ALL. Despite a relatively short period of observation, a major potential of this treatment is recognized. Longer follow-up is required to determine its overall effect on survival.
Pharmacy students' perceptions of their profession relative to other health care professions
Authors: Kritikos Vicky , Sainsbury Erica J , Bosnic-Anticevich Sinthia Z , Watt Helen M G
Published: December 2005

Objectives

(1) To investigate pharmacy students' perceptions of 10 occupations within the medical and allied professions: community pharmacists, dentists, dietitians, general medical practitioners (GPs), hospital pharmacists, medical specialists, nurses, occupational therapists, physiotherapists and social workers. (2) To explore students' perceptions of community and hospital pharmacists at different stages of a four-year undergraduate programme and at the year of pre-registration training.

Method

A 90-item questionnaire was administered to 543 pharmacy undergraduates and 95 graduates undergoing their pre-registration year training in 2001.

Setting

Faculty of Pharmacy, The University of Sydney, Australia.

Key findings

Students perceived the health care professions along three major dimensions, relating to “empathy”, “potency” and “expertise”. On an empathy dimension, students rated community pharmacists the highest and medical specialists the lowest. On a potency dimension, students rated medical specialists the most powerful, community and hospital pharmacists significantly lower, and nurses the lowest. On an expertise dimension, students rated medical specialists the highest and dietitians the lowest. A significant pattern of differences was noted in students' perceptions and a possible decline was identified in the potency rating of pharmacists at different stages of the pharmacy programme.

Conclusion

These differences may be attributed to the differences in the students' value systems, skills and experiences, the influence of reference groups and the content and structure of the educational and training programme in each year.
Schizophrenia care and the Dutch community pharmacy: the unmet needs
Authors: Rijcken C A W , de Jong-van den Berg L T W , van der Veur H , Knegtering H
Published: December 2005

Background

Schizophrenia is a severe psychiatric disease with a prevalence of 0.6% both worldwide and in the Netherlands. Without proper treatment, schizophrenia will be increasingly incapacitating for up to 70% of patients. Management consists of drug treatment and education and can include cognitive therapy. Information about antipsychotic drugs and the importance of treatment compliance are most often given to the patient by the treating psychiatrist.

Method

Structured postal questionnaires to patients and relatives - 250 members of Anoiksis, a Dutch patients' association for people suffering from psychotic illnesses and 250 members of Ypsilon, a Dutch support network for relatives of patients suffering from schizophrenia or psychosis. Face to face, semi-structured interviews with 25 community pharmacists randomly selected from different parts of the Netherlands.

Key findings

Patients and their relatives were unaware of the possible information-giving and support roles of the community pharmacist. More than 60% of patients and relatives agreed that they would have liked to receive more information about drug treatment. Two-thirds of patients and relatives thought that an active reminder to collect refill medication would be a valuable service. However, the community pharmacists were unaware of patients' unmet needs and of the support they could offer to patients with schizophrenia.

Conclusion

Patients and their relatives have needs for medication information and support that are not currently being met. Dutch community pharmacists do not currently perceive that they have a contribution to make to the care of patients with schizophrenia. As the first stage in developing future community pharmacy services, the findings of this study should be disseminated to pharmacists.

Objective

To investigate the role of the Dutch community pharmacist in schizophrenia care.
Domiciliary medication reviews by fourth year pharmacy students in Western Australia
Authors: Boyatzis Margaret , Batty Kevin T
Published: December 2005

Objective

The principal aim of this study was to assess the potential value of final-year undergraduate pharmacy students in domiciliary medication review (DMR).

Method

Students attended workshops on communication skills, complementary medicines and medication review. Each student contacted 5–10 patients by telephone and asked them to identify from memory all current medications. The student later conducted a DMR in the patient's home and prepared a report for the pharmacist preceptor and the patient's medical practitioner (GP) to review.

Results

The students recruited 189 patients, 80% of whom were over 60 years of age. The mean number of medications recalled by patients (5.8±2.9) was significantly lower than the number of medications that patients were actually taking (8.5 ± 3.5; P <0.001). Overall, 39% of patients gave incorrect/unknown indications for at least one medication and 17% had expired medicines. Students identified an average of 2.1 ± 1.7 actual or potential medication problems per patient. The mean number of problems endorsed by the pharmacist and GP were 1.1 and 0.9, and an additional 0.4 and 0.2 problems were identified, respectively. Nineteen patients (10%) required changes in therapy. Pharmacists and GPs thought it was appropriate for students to conduct DMRs under supervision and to include DMR as part of the students' training.

Conclusion

Final-year pharmacy students were capable of collecting and collating medication information for DMRs in the community setting. The programme was acceptable to patients, GPs and pharmacist preceptors. Experience in DMRs should be included in the education of pharmacy students and pre-registration trainees.
Pharmacy decision support: where is it? A systematic literature review
Authors: Calabretto Jean-Pierre , Warren Jim , Bird Linda
Published: December 2005

Objective

The objectives of this study were: to identify electronic decision supported systems that directly support pharmacists or pharmacy practice, in either the hospital or community settings; to ascertain the type of research in this area; and to identify any observable gaps for electronic decision support.

Method

A systematic literature review of PubMed, journals with known publication of decision support, databases including the Cochrane Reviews Database, selected websites and conference proceedings was conducted. Criteria for inclusion were electronic decision support systems that: were in routine use; had been used or published since 1998; provided clinical support; were not embedded into medical instruments; and were used by pharmacists in the community or hospital setting.

Key findings

Four publications met the criteria from 386 references. Of these, three described alerting systems for pharmacists, and one described the effect on pharmacist workflow of computerised prescribing. Investigation of selected websites revealed a further 20 pharmacy-related projects. It was difficult to ascertain to what extent to these (unpublished) activities were occurring in countries outside Australia (the main practice setting considered), such as the UK and Canada.

Conclusion

There is scant literature describing electronic decision support system activities specifically for pharmacy or pharmacists, in comparison to the substantial quantity of similar literature for healthcare in general. Electronic decision support activities are evident in the commercial environment for systems supporting traditional pharmacy roles. Selected conference proceedings and web-based information indicate that activity is occurring in the area of pharmacy decision support, although for relatively simple systems. The emerging patient-focused roles for pharmacists suggest that they may require similar knowledge and information to those of medical professionals. There is now a need to fully understand, define and support these pharmacist requirements, to enable appropriate decision support tools to be developed, and provide the opportunity for improved healthcare.
‘At the moment it is just a couple of eccentrics doing it’: concordance in day-to-day practice
Authors: Leontowitsch Miranda , Stevenson Fiona , Nazareth Irwin , Duggan Catherine
Published: December 2005

Objectives

To assess the feasibility and acceptability of concordance in pharmacy practice through examination of communication between customers and pharmacists in two community pharmacies in consultations for over-the-counter medicines.

Method

A qualitative pilot study involving data drawn from six sources: audiotaped training session with all the pharmacists involved, observational field work in the pharmacies, audiotaped consultations with pharmacists and customers, debriefing interviews with pharmacists after the consultation, and semi-structured interviews with customers a few days after their consultation.

Setting

Two community pharmacies that concentrate their services on medicine advice and dispensing, one in a deprived inner-city area, the other in a more affluent suburban area of London.

Key findings

The pharmacists developed a personal understanding of concordance which informed their practice. Customers reported a high level of satisfaction with services they received from the respective pharmacists. Their accounts of the consultations verified the pharmacists' patient-centredness in their day-to-day practice.

Conclusion

The implementation of a concordance model was possible through the development of a personalised, patient-centred model which drew on the model of concordance but was adapted in accordance with both structural constraints as well as the personal style of the pharmacists involved.
Molecular-Dynamics Simulation of a Methane–Oxygen Mixture: Prediction of P–V–T Data and Evaluation of Effective Pair Potential Models
Authors: Seyed Matin Naser , Jalili Amir Hossein
Published: December 2005

The results of a molecular-dynamics simulation using various isotropic pair potential functions for pure methane, oxygen, and their binary mixtures in the temperature range of 200 to 600 K and densities up to about 1.5 times their critical density is presented. The models studied in this work were: 1) Lennard–Jones (12–6) potential functions with different parameters, which have been proposed for methane and oxygen in the literature, 2) various types of Mie(n–m) potential with different values of n and m, for both methane and oxygen molecules, and 3) a potential function introduced by Dymond, Rigby, and Smith (DRS model). A Kihara–Mie(20–6) potential with the best value for the Kihara parameter, “γ” and optimized σ and ε is proposed for an oxygen molecule. Considering the predicting capability of the mentioned potential functions for pure methane and oxygen, two of them were selected for investigating methane–oxygen binary mixtures. The CH4–CH4 and O2–O2 center-of-mass radial distribution function, calculated with selected potentials, predicts the positions and peak height for g(r)CH4–CH4 and g(r)O2–O2 in good agreement with experimental data. The Deiters equation of state was used for PVT data production of pure methane and oxygen and their mixtures via imposing an intuitive mixing rule for the equation-of-state parameters. The results show good agreement between the LJ(12–6) and DRS potential models and the Deiters equation of state at densities of up to 0.25 g mL−1 at all temperatures, the deviations increasing by increasing the density. Furthermore, in the case of a methane–oxygen binary mixture, the Peng–Robinson equation of state was applied. The results reveal a strong influence of the binary interaction parameter, over the predicting ability of the Peng–Robinson equation of state for the mixture under study.
Application of Supported Liquid Membranes in the Multi-Residue Extraction of Aminoglycoside Antibiotics in Milk and Urine
Authors: Msagati Titus A M , Nindi Mathew Muzi
Published: December 2005

A supported liquid membrane has been used as a sample clean-up and/or enrichment technique in the recovery of a mixture of aminoglycoside compounds from cow’s milk and urine. The aminoglycoside compounds studied include, neomycin, gentamycin (mainly gentamycin C1a), and streptomycin. The supported liquid membrane (SLM) used to trap these compounds consisted of (1:1) 1-decanol:n-undecane. Several factors affecting the extraction efficiencies during SLM enrichment, such as donor and acceptor phases pHs, were studied. High performance liquid chromatography coupled to a positive ion electrospray-mass spectrometer was used as a detection method for these antibiotic compounds with their minor structural components. The extraction efficiencies obtained after SLM enrichment ranged between 60–90% for milk samples and 80 – ∼100% for urine matrices. The detection limits obtained from urine was 0.23 μg L−1 for neomycin, 0.31 μg L−1 for gentamycin, and 0.16 μg L−1 for streptomycin and from cow’s milk were 0.34 μg L−1 for neomycin, 0.42 μg L−1 for gentamycin, and 0.20 μg L−1 for streptomycin.