bluuebunny/crossref_metadata_2025_split huggingface dataset:
A flexibly shaped spatial scan statistic for detecting clusters
Authors: Tango Toshiro , Takahashi Kunihiko 
Published: May 2005

AbstractBackgroundThe spatial scan statistic proposed by Kulldorff has been applied to a wide variety of epidemiological studies for cluster detection. This scan statistic, however, uses a circular window to define the potential cluster areas and thus has difficulty in correctly detecting actual noncircular clusters. A recent proposal by Duczmal and Assunção for detecting noncircular clusters is shown to detect a cluster of very irregular shape that is much larger than the true cluster in our experiences.MethodsWe propose a flexibly shaped spatial scan statistic that can detect irregular shaped clusters within relatively small neighborhoods of each region. The performance of the proposed spatial scan statistic is compared to that of Kulldorff's circular spatial scan statistic with Monte Carlo simulation by considering several circular and noncircular hot-spot cluster models. For comparison, we also propose a new bivariate power distribution classified by the number of regions detected as the most likely cluster and the number of hot-spot regions included in the most likely cluster.ResultsThe circular spatial scan statistics shows a high level of accuracy in detecting circular clusters exactly. The proposed spatial scan statistic is shown to have good usual powers plus the ability to detect the noncircular hot-spot clusters more accurately than the circular one.ConclusionThe proposed spatial scan statistic is shown to work well for small to moderate cluster size, up to say 30. For larger cluster sizes, the method is not practically feasible and a more efficient algorithm is needed.
Health-related quality of life measurement in pediatric clinical practice: An appraisal and precept for future research and application
Authors: Varni James W , Burwinkle Tasha M , Lane Mariella M 
Published: May 2005

AbstractHealth-related quality of life (HRQOL) measurement has emerged as an important health outcome in clinical trials, clinical practice improvement strategies, and healthcare services research and evaluation. HRQOL measures are also increasingly proposed for use in clinical practice settings to inform treatment decisions. In settings where HRQOL measures have been utilized with adults, physicians report such measures as useful, some physicians alter their treatment based on patient reports on such instruments, and patients themselves generally feel the instruments to be helpful. However, there is a dearth of studies evaluating the clinical utility of HRQOL measurement in pediatric clinical practice. This paper provides an updated review of the literature and proposes a precept governing the application of pediatric HRQOL measurement in pediatric clinical practice. Utilizing HRQOL measurement in pediatric healthcare settings can facilitate patient-physician communication, improve patient/parent satisfaction, identify hidden morbidities, and assist in clinical decision-making. Demonstrating the utility of pediatric HRQOL measurement in identifying children with the greatest needs, while simultaneously demonstrating the cost advantages of providing timely, targeted interventions to address those needs, may ultimately provide the driving force for incorporating HRQOL measurement in pediatric clinical practice.
Cytoskeleton reorganization mediates alpha6beta1 integrin-associated actions of laminin on proliferation and survival, but not on steroidogenesis of ovine granulosa cells
Authors: Bellego Frédérique Le , Fabre Stéphane , Pisselet Claudine , Monniaux Danielle 
Published: May 2005

Abstract

Background
Laminin (LN) is one of the most abundant extracellular matrix components of the basal lamina and granulosa cell layers of ovarian follicles. Culture of ovine granulosa cells (GC) on LN substratum induces cell spreading, enhances cell survival and proliferation, and promotes luteinization. Previous investigations have shown that these effects are mostly mediated by the alpha6beta1 integrin, but its signalization pathways have not been investigated. This study aimed to assess the importance of the cytoskeleton in the alpha6beta1 integrin-mediated actions of laminin on survival, proliferation and steroidogenesis of ovine GC.

Methods
The relationships between morphology and functions of ovine GC cultured on substrata containing LN or/and RGD peptides were investigated. The effects of (1) cytochalasin D, an actin cytoskeleton-disrupting drug, (2) a specific function-blocking antibody raised against alpha6 integrin subunit (anti-alpha6 IgG), and (3) an inhibitor of the ERK1/2 signalization pathway (PD98059) were assessed for GC shape, pyknosis and proliferation rates, oestradiol and progesterone secretions.

Results
Cytoskeleton disruption by cytochalasin D induced cell rounding, inhibited proliferation, promoted pyknosis, inhibited progesterone secretion and enhanced oestradiol secretion by GC cultured on LN. When GC were cultured on various substrata containing LN and/or RGD peptides in the presence or absence of anti-alpha6 IgG, both the existence of close correlations between the percentage of round cells, and the GC proliferation rate (r = -0.87) and pyknotic rate (r = 0.76) were established, but no relationship was found between cell shape and steroidogenesis. Inhibition of the ERK1/2 signalization pathway by PD98059 had no effect on GC shape, proliferation or pyknotic rates. However, it dramatically reduced progesterone secretion, expression of cytochrome P450 cholesterol side-chain cleavage and 3beta-hydroxysteroid deshydrogenase enzymes, and enhanced oestradiol secretion, thereby reproducing all the effects of the anti-alpha6 IgG on steroidogenesis of GC cultured on LN.

Conclusion
LN may participate in the paracrine control of follicular development through different mechanisms. It could enhance proliferation and survival of GC through its alpha6beta1 integrin-mediated actions on cytoskeleton. In contrast, its stimulating action on GC luteinization could be partly mediated by the ERK1/2 pathway, irrespective of cell shape.
Gene expression profile and synovial microcirculation at early stages of collagen-induced arthritis
Authors: Gierer Philip , Ibrahim Saleh , Mittlmeier Thomas , Koczan Dirk , Moeller Steffen , Landes Jürgen , Gradl Georg , Vollmar Brigitte 
Published: May 2005

AbstractA better understanding of the initial mechanisms that lead to arthritic disease could facilitate development of improved therapeutic strategies. We characterized the synovial microcirculation of knee joints in susceptible mouse strains undergoing intradermal immunization with bovine collagen II in complete Freund's adjuvant to induce arthritis (i.e. collagen-induced arthritis [CIA]). Susceptible DBA1/J and collagen II T-cell receptor transgenic mice were compared with CIA-resistant FVB/NJ mice. Before onset of clinical symptoms of arthritis, in vivo fluorescence microscopy of knee joints revealed marked leucocyte activation and interaction with the endothelial lining of synovial microvessels. This initial inflammatory cell response correlated with the gene expression profile at this disease stage. The majority of the 655 differentially expressed genes belonged to classes of genes that are involved in cell movement and structure, cell cycle and signal transduction, as well as transcription, protein synthesis and metabolism. However, 24 adhesion molecules and chemokine/cytokine genes were identified, some of which are known to contribute to arthritis (e.g. CD44 and neutrophil cytosolic factor 1) and some of which are novel in this respect (e.g. CC chemokine ligand-27 and IL-13 receptor α1). Online in vivo data on synovial tissue microcirculation, together with gene expression profiling, emphasize the potential role played by early inflammatory events in the development of arthritis.
Drotrecogin alfa (activated) in patients with severe sepsis presenting with purpura fulminans, meningitis, or meningococcal disease: a retrospective analysis of patients enrolled in recent clinical studies
Authors: Vincent Jean-Louis , Nadel Simon , Kutsogiannis Demetrios J , Gibney RT Noel , Yan S Betty , Wyss Virginia L , Bailey Joan E , Mitchell Carol L , Sarwat Samiha , Shinall Stephen M , Janes Jonathan M 
Published: May 2005

Abstract
Introduction
We report data from adult and pediatric patients with severe sepsis from studies evaluating drotrecogin alfa (activated) (DrotAA) and presenting with purpura fulminans (PF), meningitis (MEN), or meningococcal disease (MD) (PF/MEN/MD). Such conditions may be associated with an increased bleeding risk but occur in a relatively small proportion of patients presenting with severe sepsis; pooling data across clinical trials provides an opportunity for improving the characterization of outcomes.

Methods
A retrospective analysis of placebo-controlled, open-label, and compassionate-use trials was conducted. Adult patients received infusions of either DrotAA or placebo. All pediatric patients (<18 years old) received DrotAA. 189 adult and 121 pediatric patients presented with PF/MEN/MD.

Results
Fewer adult patients with PF/MEN/MD met cardiovascular (68.3% versus 78.8%) or respiratory (57.8% versus 80.5%) organ dysfunction entry criteria than those without. DrotAA-treated adult patients with PF/MEN/MD (n = 163) had an observed 28-day mortality rate of 19.0%, a 28-day serious bleeding event (SBE) rate of 6.1%, and an intracranial hemorrhage (ICH) rate of 4.3%. Six of the seven ICHs occurred in patients with MEN (three of whom were more than 65 years old with a history of hypertension). DrotAA-treated adult patients without PF/MEN/MD (n = 3,088) had an observed 28-day mortality rate of 25.5%, a 28-day SBE rate of 5.8%, and an ICH rate of 1.0%. In contrast, a greater number of pediatric patients with PF/MEN/MD met the cardiovascular organ dysfunction entry criterion (93.5% versus 82.5%) than those without. DrotAA-treated PF/MEN/MD pediatric patients (n = 119) had a 14-day mortality rate of 10.1%, an SBE rate of 5.9%, and an ICH rate of 2.5%. DrotAA-treated pediatric patients without PF/MEN/MD (n = 142) had a 14-day mortality rate of 14.1%, an SBE rate of 9.2%, and an ICH rate of 3.5%.

Conclusion
DrotAA-treated adult patients with severe sepsis presenting with PF/MEN/MD had a similar SBE rate, a lower observed 28-day mortality rate, and a higher observed rate of ICH than DrotAA-treated patients without PF/MEN/MD. DrotAA-treated pediatric patients with severe sepsis with PF/MEN/MD may differ from adults, because all three outcome rates (SBE, mortality, and ICH) were lower in pediatric patients with PF/MEN/MD.
Polymorphisms of the renin-angiotensin system genes in Brazilian patients with lupus nephropathy
Authors: Sprovieri S RS , Sens Y AS 
Published: May 2005

Genetic polymorphisms of the renin-angiotensin system (RAS) has been associated with cardiovascular events and the progression of nephropathy in several diseases. The objective of this study was to evaluate a possible association of the genetic polymorphisms of RAS with the development and/or progression of lupus nephritis in a Brazilian population. Seventy-five SLE patients with lupus nephropathy (LN group) were compared to 72 SLE patients without LN (SLE group) and 65 healthy individuals (CONTROL group), of sex and ethnic matched, in a Brazilian population sample. Mean global follow-up was 9 + 6 years for lupus without nephropathy and 11 + 7 years for lupus nephropathy. Following the extraction of genomic DNA from the leukocytes in the peripheral blood, angiotensin converting enzyme (ACE I/D), angiotensinogen (AGT M235T) and angiotensin II type 1 receptor (AGTR1 A1166C) genotypes were determined by the polymerase chain reaction. No significant difference of ACE, AGT and AGTR1 genotypes distribution between groups was observed in this study. There was no significant association between the variables of the RAS genotypes and the presence of hypertension in SLE. However, an increased frequency of DD genotype (ACE I/D) was observed in SLE patients with LN who progressed to CRF compared to healthy controls (DD 60%, DI 26.7%, II 13.3% versus 27.7%, 60% and 12.3%, respectively; x2 = 6.299, P = 0.0429). In the population studied, there was no influence of the RAS genetic polymorphisms in the development of lupus nephropathy, but the progression to CRF was associated with ACE DD polymorphism.
The effect of freeze-drying with different cryoprotectants and gamma-irradiation sterilization on the characteristics of ciprofloxacin HCl-loaded poly(D,L-lactide-glycolide) nanoparticles
Authors: Bozdag S , Dillen K , Vandervoort J , Ludwig A 
Published: May 2005

Abstract
In the present study, the influence of freeze-drying with several cryoprotective agents and gamma (γ)-irradiation sterilization on the physicochemical characteristics of ciprofloxacin HCl-loaded poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles was evaluated. Nanoparticles were prepared by W/O/W emulsification solvent evaporation followed by high-pressure homogenization. They were freeze-dried in the presence of 5.0% (w/v) mannitol, trehalose or glucose, with 5.0% (w/v) or 15.0% (w/v) dextran as cryoprotectants. The nanoparticles were irradiated at a dose of 25 kGy using a 60Co source. The following physicochemical properties of the formulations were investigated: the ratio of particle size before (initial) and after freeze-drying, the ease of reconstitution of the nanoparticle suspensions and the drug-release profiles of irradiated and non-irradiated nanoparticles. The anti-bacterial activity against Pseudomonas aeruginosa was measured. The freeze-drying process induced a significant increase in particle size when no cryoprotectant was employed. Similar results were observed when cryoprotectants were added to the formulation. Only when mannitol was used was no significant size increase measured. Moreover, for formulations with dextran, reconstitution after freeze-drying was difficult by manual agitation and particle size could not be determined because of aggregation. After γ-sterilization no significant difference in mean particle size was observed, but reconstitution was more difficult and drug release was influenced negatively. Ciprofloxacin HCl incorporated in the nanoparticles was still effective against the micro-organism selected after freeze-drying and γ-sterilization.
Green tea polyphenols and dietary fibre protect against kidney damage in rats with diabetic nephropathy
Authors: Yokozawa Takako , Nakagawa Takako , Oya Takeshi , Okubo Tsutomu , Juneja Lekh Raj 
Published: May 2005

Abstract
In this study we examined the effect of green tea polyphenols (GTP) and partially hydrolysed guar gum (PHGG) as dietary fibre on diabetic nephropathy, using rats that had been subjected to subtotal nephrectomy and injection of streptozotocin. The subtotally nephrectomized rats were subjected to resection of three-quarters of the kidney. Rats with diabetic nephropathy were divided into four groups: untreated controls, and animals that received GTP (100 mg kg−1 body weight day−1), PHGG (100 mg kg−1 body weight day−1) and GTP plus PHGG (50 mg kg−1 body weight day−1 plus 50 mg kg−1 body weight day−1). After 50 days of administration, attenuation of urinary protein excretion and the morphological changes peculiar to diabetic nephropathy were observed in all three treated groups. Furthermore, the group treated with GTP plus PHGG showed an improvement of kidney weight and serum levels of urea nitrogen, creatinine and creatinine clearance. Hyperglycaemia, as assessed in terms of blood glucose and glycosylated protein levels, was also improved by administration of GTP plus PHGG. On the other hand, GTP administration increased the activity of superoxide dismutase in the kidney to a significant extent. A significant reduction in the total cholesterol concentration was also observed in the PHGG-treated group. These results suggest that GTP and PHGG could be beneficial as additional therapy in the management of diabetic nephropathy.
The adherence to antiretroviral treatment evaluated from a hospital pharmacy: importance of the protease inhibitors pharmacological class
Authors: Rubio M , Pédeboscq S , Ekouevi D , Zalabadi K , Chêne G , Bonarek M , Pometan J P 
Published: May 2005

The goal of this study was to develop an evaluation method of antiretroviral treatment adherence from a hospital pharmacy and to identify one or more factors that influenced this adherence, such as patient or treatment characteristics. The HIV patients included in this study were based, for the major part, in Saint-André hospital and collected their medication from this hospital pharmacy. They were all delivered a renewable prescription that should have comprised two successive delivery stamps. A total of 186 patients was included. For the adherence analysis, the delay between two successive deliveries was measured. We have specified three different categories of patients: adherent, non-adherent and intermediate, according to a definition of adherence accepted by many authors. We have demonstrated that the only antiretroviral therapeutic class associated with poor adherence was the protease inhibitors, in particular nelfinavir, which requires food to be taken at the time of administration. This can pose difficulties for those patients who lunch at their workplace and consequently affect adherence. This study allowed us to demonstrate that a less subjective adherence evaluation can be easily carried out from a hospital pharmacy.
Acceptance of flexible sigmoidoscopy and colonoscopy for screening and surveillance in colorectal cancer prevention
Authors: Nicholson Fiona B , Korman Melvyn G 
Published: May 2005

Objectives: To study an individual's experience of either flexible sigmoidoscopy (FS) or colonoscopy in a colorectal cancer prevention programme. Methods: Consecutive individuals in a Bowel Cancer Prevention Programme, who had either an unsedated FS or a colonoscopy with sedation, participated in a prospective cross-sectional questionnaire-based study. Results: A total of 447 responses were obtained for 256 colonoscopies and 191 FSs (200 men [45%] and 247 women [55%]). The overall experience of colonoscopy was more comfortable than FS (75% versus 18%; P<0.001). Embarrassment was low for both procedures (8%). There was no pain associated with colonoscopy and most individuals had a pain score of less than 3 (11-point scale) for FS: 72% of men, 55% of women ( P<0.001). Most individuals did not have a gender preference for the endoscopist. For colonoscopy, the worst part of the procedure was the preparation (78%) and for FS the preparation and the procedure ranked equally worst (30%). Conclusions: We have shown that colonoscopy with sedation is a very comfortable procedure. FS is more uncomfortable than colonoscopy; however, for the majority it is a tolerable experience. Women found FS only slightly more painful than men. The worst part of either procedure was the preparation. Embarrassment with either procedure was minimal. Both procedures are well tolerated and suitable for colorectal cancer screening.
Herbal Therapy in Primary Health Care in Maracanaú, Ceará, Brazil
Authors: Silva Maria IG , Sousa Francisca CF , Gondim Ana PS 
Published: May 2005

BACKGROUND The public health system in Brazil is insufficient to provide basic pharmaceutical and medical care to the population. Currently, some herbal therapy programs are being developed in primary healthcare services to supply the communities lacking basic medicines. OBJECTIVE To investigate the use of herbal medicines in primary health care in Maracanaú, a northeast Brazilian city. METHODS A descriptive cross-sectional study was conducted in family health care units in Maracanaú during August and September of 2002. Two hundred twenty-six patients were interviewed via structured questionnaire. Descriptive statistical analysis was accomplished using sample size and proportions. χ 2 And Student's t-tests were used to compare percentages and means, respectively. RESULTS Among the 226 patients interviewed, 144 (63.7%) reported previous use of herbal medicines. Among those, 131 (90.9%) observed therapeutic benefits from herbal medicines. We identified 10 types of herbal medicines in the prescriptions, including syrups, dyes, capsules, and ointments, for the treatment of respiratory problems (63.8%), skin conditions (15.3%), diabetes mellitus (11.4%), and other illnesses. Further, we observed that some herbal medicines were not being produced during the study period and that several patients were not aware of the fact that they were receiving herbal medicine. CONCLUSIONS Data support the use of herbal therapy in primary health care in Maracanaú. However, there is a need to conduct further study on the efficacy and safety of these herbal medicines, as well as on their quality control.
Interpretation of Medication Pictograms by Adults in the UK
Authors: Knapp Peter , Raynor David K , Jebar Adel H , Price Sarah J 
Published: May 2005

BACKGROUND Patients' ability to understand information about medication is crucial for safety and effectiveness. Rates of illiteracy worldwide indicate that written information alone cannot meet many patients' needs. Medication pictograms are an alternative, but may be culturally sensitive. Previous testing has used large pictograms, which are impractical for conventional drug information formats. OBJECTIVE To compare 2 sets of pictograms for instructions or warnings (from the US and South Africa) for understandability by adults in the UK and examine the effects of pictogram size and repeat presentation on understandability among older adults. METHODS In the first part of the study, 160 adults (aged 17–83 y) reviewed and interpreted 10 pictograms. In the second, 67 older adults (aged 65–96 y) were randomly assigned to review 10 small or large pictograms. After giving their interpretation, they were informed of the correct meaning. One week later, they were shown the same pictograms and gave their interpretation. RESULTS The pictograms for the 10 different instructions and warnings showed great variation in interpretation rates (7.5–90%), with few significant differences between the US and South African versions. Only 3 were understood by ≥85% of the population. Pictograms performed significantly better if they were larger and at the second presentation. CONCLUSIONS Pictograms have the potential to help patients understand information on drug therapy. This study shows that some existing pictograms are not easily interpreted and that testing is needed before their implementation. A reduction in their size to allow incorporation into conventional written formats may cause additional problems for patients.