bluuebunny/crossref_metadata_2025 huggingface dataset:
Insurgency and Spaces of Active Citizenship
Authors: Miraftab Faranak , Wills Shana
Published: November 2005

This article concerns the struggle waged by the poor in Cape Town, South Africa, to assert their constitutional rights to shelter and basic services and protect their life spaces against neoliberal policies. Using insurgent urbanism and active citizenship as its conceptual guide, this article attempts to enhance understanding of grass-roots spaces for practicing inclusive citizenship, stretching beyond a limited interpretation of formal citizen participation. Through the example of the Western Cape Anti-eviction Campaign in South Africa, the article aims to contribute to a recent opening in the planning inquiry by overcoming the selective definition of what constitutes civil society and public participation and underlining the significance of invited and invented spaces of citizen participation in the formation of inclusive citizenship and just cities.
Comparative Quantitative Acid-Base Analysis in Coronary Artery Bypass, Severe Sepsis, and Diabetic Ketoacidosis
Authors: Omron Edward M.
Published: November 2005

The main objective of this study was to assess the relationship of standard base excess (SBE) to delta strong ion difference effective (ΔSIDe) in critical illness. Critical illness is characterized by variable plasma nonvolatile weak acid components (ΔA-), and SBE becomes discordant with ΔSIDe. The author hypothesized that both acid-base models are equivalent when SBE and ΔSIDe are corrected for ΔA-. A retrospective chart review was performed to assess this hypothesis by looking at changes in SBE, ΔSIDe, and ΔA-in 30 coronary artery bypass graft surgery patients, 30 severe sepsis patients, and 15 diabetic ketoacidosis patients. SBE equals the sum of the ΔSIDe and ΔA-. The SBE quantifies the magnitude of the metabolic acid-base derangement, the ΔSIDe quantifies the plasma strong cation/anion imbalance, and the ΔA-quantifies the magnitude of the hypoalbuminemic alkalosis. The partitioning of SBE into physicochemical components can facilitate analyses of complex acid-base disorders in critical illness.
The Use of Ultrasound to Characterize Milk Ejection in Women Using an Electric Breast Pump
Authors: Ramsay Donna T. , Mitoulas Leon R. , Kent Jacqueline C. , Larsson Michael , Hartmann Peter E.
Published: November 2005

This study aimed to use ultrasound imaging to investigate the milk ejection characteristics of women during a 10-minute expression using an electric breast pump capable of applying 2 markedly different vacuum patterns. The classic pattern (47 cycles/min) and 3-phase pattern (pre-milk ejection: 120 cycles/min, post-milk ejection: 20 cycles/min for 2 minutes post-milk ejection then 55-78 cycles/min for 8 minutes) were tested, and the milk expressed was collected in 30-second intervals. Multiple milk ejections (96%) were detected (classic: 3.27 ± 2.05; 3-phase: 3.72 ± 1.19) and associated with increases in milk flow. Almost half of the total volume of milk expressed was removed during the first milk ejection (classic: 41.38 ± 21.48%; 3-phase: 46.72 ± 26.60%). There was no correlation between the number of milk ejections and both the total volume of milk and percentage of available milk for either pattern. In conclusion, milk ejection characteristics and efficiency of milk expression did not change in response to different expression patterns.
A Breastfeeding Curriculum for Residents and Medical Students: A Multidisciplinary Approach
Authors: Ogburn Tony , Espey Eve , Leeman Larry , Alvarez Kathy
Published: November 2005

Medical school and residency training programs, in which practice patterns are established, frequently lack formal education in breastfeeding in the United States. This project, a curriculum based on the Wellstart Lactation Management Guide, was developed for resident physicians and medical students at the University of New Mexico to address the deficiency in formal education about breastfeeding. The curriculum, developed and implemented by faculty members from obstetrics/gynecology, pediatrics, and family medicine, includes formal interactive teaching sessions, discussion of breastfeeding issues on daily clinical rounds, and patient visits with lactation support personnel. Interns from the Departments of Pediatrics, Obstetrics/Gynecology, and Family Medicine participate. Surveys of participating residents and faculty demonstrate highly favorable attitudes. In conclusion, a multidisciplinary approach to breastfeeding education is feasible and well received by both teachers and residents. J Hum Lact. 21(4):458-464.
Clinical Pharmacokinetic and Pharmacodynamic Monitoring for Mycophenolate Mofetil
Authors: Ku Yi-Min , McCartan Megan , Collier Dean
Published: November 2005

The use of mycophenolate mofetil (MMF), in combination with cyclosporine (CsA) or tacrolimus (FK) and corticosteroids, has been shown to improve clinical outcomes through significant reduction in the incidence of acute rejection in solid organ transplant patients. A fixed oral dosing regimen of 1 or 1.5 g MMF twice daily received Food and Drug Administration approval in 1995 with no recommendations for concentration monitoring at that time. Subsequent evidence has generated substantial debate on the need of clinical monitoring for MMF. This article summarizes the rationale, evidence, and approaches of clinical monitoring for MMF. Mycophenolic acid (MPA), the active moiety of MMF, noncompetitively inhibits the enzyme inosine monophosphate dehydrogenase (IMPDH), which is the target enzyme for MPA. Pharmacokinetic monitoring, by use of MPA predose or MPA area under the concentration-time curve (AUC) values, and pharmacodynamic monitoring by analysis of inhibition of IMPDH have been evaluated in organ transplant patients. The possibility of drug interactions between other immunosuppressive agents has also received attention recently. The clinical implications of drug interactions are discussed in this article.
The nature of poverty in the garrison constituencies in Jamaica
Authors: Henry-Lee Aldrie
Published: November 2005

In 2001, 16.9 per cent of the population in Jamaica was living in poverty, down from 30.5 per cent in 1989. Jamaica is well on its way to achieving the first Millennium Development Goal of halving by 2015 the number of persons living in extreme poverty. However, policy makers are particularly concerned about the persistent high levels of poverty in the rural areas. This paper argues that although the incidence of urban poverty has been consistently lower than that of rural poverty, there are certain urban areas that warrant special policy attention. In spite of a reduction in poverty at the macro level in these “garrison constituencies”, the quality of life for the residents has not improved significantly, and any sustained improvement will be extremely difficult given the quality of their political and social capital. There has been no sustained political will to dismantle these garrison constituencies, and everyday life is deeply entrenched in crime, violence and political patronage. Unless there are deliberate and well-targeted policies to dismantle these constituencies and break the stranglehold that the political and criminal elements have on the residents, then they will never experience any sustained improvement in their quality of life.
Institutional and legal aspects of urban agriculture in French-speaking West Africa: from marginalization to legitimization
Authors: Cissé Oumar , Gueye Ndèye Fatou Diop , Sy Moussa
Published: November 2005

Although urban agriculture has long been marginalized or ignored on the assumption that it is not an appropriate urban activity, it is attracting increasing interest among public authorities, civil society and researchers. This paper reports on research and city consultations in seven West African cities, which examined the institutional aspects of urban agriculture, including the constraints it faces. The paper discusses the growing interest by public authorities in urban agriculture, and the fact that this has failed to lead to its effective consideration in the institutional and legal provisions of most West African countries. Moreover, decentralization processes in the region have not led to a commitment by city governments to support urban agriculture. The uncertain legal status of urban agriculture contrasts with the multiplicity of actors who intervene directly or indirectly in its promotion and development. Despite problems of coordination between various sectors and levels of government, and a failure to achieve the necessary functional complementarity (for instance, between land management, agriculture and water, and waste management) the multiplicity and diversity of actors involved in urban agriculture are the expressions of its added value in both social and economic terms.
The impact of privatization of solid waste management on the Zabaleen garbage collectors of Cairo
Authors: Fahmi Wael Salah
Published: November 2005

This paper investigates the recently launched privatization of local solid waste management in Cairo, focusing on its adverse effects on the economy and on the urban settlement system of the Zabaleen garbage collectors’ communities. According to the official development strategy, the privatization of solid waste services is fundamental to overall government plans for the rehabilitation of areas of historical Cairo. But the objectives of the rehabilitation plans tend to favour business interests while threatening the interests of the local population. The findings of a study on the situation emphasize the significance of poverty alleviation initiatives in restructuring solid waste collection and developing the recycling industry, and the development of new channels for cooperation and partnership between the garbage collectors’ association (Gammiya), grassroots organizations, local authorities and multinational waste management companies. In order to promote sustainable livelihoods and better opportunities for the urban poor, the study emphasizes the need among the low-income Zabaleen to draw on the sustainable flow of local resources, while seeking new means of supporting land acquisition and its development for improved housing standards, basic services and environmental quality.
Video game play in British and Japanese adolescents
Authors: Colwell John , Kato Makiko
Published: November 2005

Results from research into negative correlates of computer/video game play in the United Kingdom and in Japan are presented, with new analyses across cultures. Patterns of play are similar, although Japanese adolescents have been playing for longer, they play fewer aggressive games, and there is greater perceived concern by Japanese parents. Principal components analyses of a scale to measure needs met by game play produce essentially the same factors: “companionship,” which correlates with play in the United Kingdomonly, and “prefer to friends,” which in Japan correlates with play for both genders, but only for boys in the United Kingdom. Aggression scores are predicted by frequency of play in both cultures, but years of play explain none of the variance. A preference for aggressive games predicts lower aggression scores in Japan. These findings would seem to provide little support for the causal link hypothesis.
Contexts, gaming pleasures, and gendered preferences
Authors: Carr Diane
Published: November 2005

In this article, the author explores computer gaming preferences of girls through observations of a games club at an all-girl state school in the United Kingdom. The author argues that gaming tastes are alterable and site specific. Gaming preferences certainly relate to the attributes of particular games, but they will also depend on the player’s recognition and knowledge of these attributes. Players accumulate these competencies according to the patterns of access and peer culture they encounter. The constituents of preference, such as access, are shaped by gender, and as a result, gaming preferences may manifest along gendered lines. It is not difficult to generate data, indicating that gendered tastes exist, but it is shortsighted to separate such outcomes from the various practices that contribute to their formation.
Bridging the methodological divide in game research
Authors: Williams Dmitri
Published: November 2005

The study of video game effects has been marked by two very different approaches. The first approach is represented by social scientists, who, with some exceptions, seek to understand the effects of games on users. The second approach is favored by humanists, who seek to understand the meaning and context of games. To date, these two groups have largely talked past one another due to their different goals and their different methodologies. Yet, for the advancement of science and understanding, both sets of scholarship are important and relevant. Each has contributions to make. However, unless these two groups come to possess at least a cursory understanding of the other’s methodology, there will be little synthesis. This is a missed opportunity for scholars of every stripe, and ways are suggested to bridge these gaps.!
Endogenous fantasy and learning in digital games
Authors: Habgood M. P. J. , Ainsworth S. E. , Benford S.
Published: November 2005

Many people believe that educational games are effective because they motivate children to actively engage in a learning activity as part of playing the game. However, seminal work by Malone, exploring the motivational aspects of digital games, concluded that the educational effectiveness of a digital game depends on the way in which learning content is integrated into the fantasy context of the game. In particular, he claimed that content that is intrinsically related to the fantasy will produce better learning than that which is merely extrinsically related. However, this distinction between intrinsic and extrinsic (or endogenous and exogenous) fantasy is a concept that has developed a confused standing over the following years. This article will address this confusion by providing a review and critique of the empirical and theoretical foundations of endogenous fantasy and its relevance to creating educational digital games. Substantial concerns are raised about the empirical basis of this work and a theoretical critique of endogenous fantasy is offered, concluding that endogenous fantasy is a misnomer, insofar as the “integral and continuing relationship” of fantasy cannot be justified as a critical means of improving the effectiveness of educational digital games. An alternative perspective on the intrinsic integration of learning content is described, incorporating game mechanics, flow, and representations.
Alternative splicing and protein function
Authors: Neverov AD , Artamonova II , Nurtdinov RN , Frishman D , Gelfand MS , Mironov AA
Published: November 2005

Background

Alternative splicing is a major mechanism of generating protein diversity in higher eukaryotes. Although at least half, and probably more, of mammalian genes are alternatively spliced, it was not clear, whether the frequency of alternative splicing is the same in different functional categories. The problem is obscured by uneven coverage of genes by ESTs and a large number of artifacts in the EST data.

Results

We have developed a method that generates possible mRNA isoforms for human genes contained in the EDAS database, taking into account the effects of nonsense-mediated decay and translation initiation rules, and a procedure for offsetting the effects of uneven EST coverage. Then we computed the number of mRNA isoforms for genes from different functional categories. Genes encoding ribosomal proteins and genes in the category "Small GTPase-mediated signal transduction" tend to have fewer isoforms than the average, whereas the genes in the category "DNA replication and chromosome cycle" have more isoforms than the average. Genes encoding proteins involved in protein-protein interactions tend to be alternatively spliced more often than genes encoding non-interacting proteins, although there is no significant difference in the number of isoforms of alternatively spliced genes.

Conclusion

Filtering for functional isoforms satisfying biological constraints and accountung for uneven EST coverage allowed us to describe differences in alternative splicing of genes from different functional categories. The observations seem to be consistent with expectations based on current biological knowledge: less isoforms for ribosomal and signal transduction proteins, and more alternative splicing of interacting and cell cycle proteins.
Methylenetetrahydrofolate reductase polymorphism 677C>T is associated with peripheral arterial disease in type 2 diabetes
Authors: Pollex Rebecca L , Mamakeesick Mary , Zinman Bernard , Harris Stewart B , Hanley Anthony JG , Hegele Robert A
Published: November 2005

Background

Individuals with diabetes are twice as likely to develop peripheral arterial disease (PAD), the manifestation of extensive atherosclerosis throughout the lower extremities. One putative determinant of PAD is the 677C>T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR), which has previously been found to associate with various diabetic complications including retinopathy, nephropathy, atherosclerosis and coronary heart disease. The objective of this study was to investigate a possible role for the MTHFR 677C>T gene polymorphism with PAD in subjects with type 2 diabetes from an isolated aboriginal Canadian population.

Methods

The 677C>T MTHFR gene polymorphism was genotyped in 138 subjects of Oji-Cree descent. Participants were selected from a community-wide survey that included PAD assessment by ankle-brachial index (ABI) measurement, and also intermittent claudication assessment by the Rose questionnaire.

Results

MTHFR 677T allele carriers had an increased risk of PAD with an odds ratio of 3.54 (95% CI 1.01, 12.4), P = 0.049, after adjustment for age, sex, duration of diabetes, hypertension, current smoking habits, and use of insulin or oral treatment for diabetes. None of these additional co-variables was significantly associated with PAD. No association was found between MTHFR genotype and intermittent claudication.

Conclusion

The genetic influence of the MTHFR 677C>T genotype on diabetic PAD is modest, yet for the Oji-Cree it is a major risk factor in comparison to other traditional risk factors.
Malaria chemoprophylaxis and the serologic response to measles and diphtheria-tetanus-whole-cell pertussis vaccines
Authors: Rosen Jennifer B , Breman Joel G , Manclark Charles R , Meade Bruce D , Collins William E , Lobel Hans O , Saliou Pierre , Roberts Jacquelin M , Campaoré Pierre , Miller Mark A
Published: November 2005

Background

Acute malaria has been associated with a decreased antibody response to tetanus and diphtheria toxoids, meningococcal, salmonella, and Hib vaccines. Interest in giving malaria drug therapy and prevention at the time of childhood immunizations has increased greatly following recent trials of intermittent preventive therapy during infancy (IPTi), stimulating this re-analysis of unpublished data. The effect of malaria chemoprophylaxis on vaccine response was studied following administration of measles vaccines and diphtheria-tetanus-whole cell pertussis (DTP) vaccines.

Methods

In 1975, six villages divided into two groups of children ≤74 months of age from Burkina Faso, were assigned to receive amodiaquine hydrochloride chemoprophylaxis (CH+) every two weeks for seven months or no chemoprophylaxis (CH-). After five months, children in each group received either one dose of measles or two doses of DTP vaccines.

Results

For recipients of the measles vaccine, the seroconversion rates in CH+ and CH- children, respectively, were 93% and 96% (P > 0.05). The seroresponse rates in CH+ and CH- children respectively, were 73% and 86% for diphtheria (P > 0.05) and 77% and 91% for tetanus toxoid (P > 0.05). In a subset analysis, in which only children who strictly adhered to chemoprophylaxis criteria were included, there were, likewise, no significant differences in seroconversion or seroresponse for measles, diphtheria, or tetanus vaccines (P > 0.05). While analysis for pertussis showed a 43% (CH+) and 67% (CH-) response (P < 0.05), analyses using logistic regression to control for sex, age, chemoprophylaxis, weight-for-height Z-score, and pre-vaccination geometric mean titer (GMT), demonstrated that chemoprophylaxis was not associated with a significantly different conversion rate following DTP and measles vaccines. Seven months of chemoprophylaxis decreased significantly the malaria IFA and ELISA GMTs in the CH+ group.

Conclusion

Malaria chemoprophylaxis prior to vaccination in malaria endemic settings did not improve or impair immunogenicity of DTP and measles vaccines. This is the first human study to look at the association between malaria chemoprophylaxis and the serologic response to whole-cell pertussis vaccine.
Evolution of subtype C HIV-1 Env in a slowly progressing Zambian infant
Authors: Zhang Hong , Hoffmann Federico , He Jun , He Xiang , Kankasa Chipepo , Ruprecht Ruth , West John T , Orti Guillermo , Wood Charles
Published: November 2005

Background

Given the high prevalence of mother to child infection, the development of a better understanding of African subtype C HIV-1 transmission and natural evolution is of significant importance. In this study, we genotypically and phenotypically characterized subtype C viruses isolated over a 67-month follow-up period from an in utero-infected Zambian infant. Changes in genotype and phenotype were correlated to alterations of the host humoral immune response.

Results

A comparison of baseline maternal and infant samples indicated that the infant sequences are monophyletic and contain a fraction of the diversity observed in the mother. This finding suggests that selective transmission occurred from mother to child. Peaks in infant HIV-1 Env genetic diversity and divergence were noted at 48 months, but were not correlated with changes in co-receptor usage or syncytia phenotype. Phylogenetic analyses revealed an accumulation of mutations over time, as well as the reappearance of ancestral lineages. In the infant C2-V4 region of Env, neither the median number of putative N-glycosylation sites or median sequence length showed consistent increases over time. The infant possessed neutralizing antibodies at birth, but these decreased in effectiveness or quantity with time. De novo humoral responses were detected in the child after 12 months, and corresponded with an increase in Env diversity.

Conclusion

Our study demonstrates a correlation between HIV-1 Env evolution and the humoral immune response. There was an increase in genetic diversification in the infant viral sequences after 12 months, which coincided with increases in neutralizing antibody titers. In addition, episodes of viral growth and successive immune reactions in the first 5–6 years were observed in this slow progressor infant with delayed onset of AIDS. Whether this pattern is typical of slow progressing subtype C HIV-1 infected infant needs to be further substantiated.
Development of a health care policy characterisation model based on use of private health insurance
Authors: Moorin Rachael E , Holman C D'Arcy J
Published: November 2005

Objective

The aim of this study was to develop a policy characterisation process based on measuring shifts in use of private health insurance (PHI) immediately following implementation of changes in federal health care policy.

Method

Population-based hospital morbidity data from 1980 to 2001 were used to produce trend lines in the annual proportions of public, privately insured and privately uninsured hospital separations in age-stratified subgroups. A policy characterisation model was developed using visual and statistical assessment of the trend lines associated with changes in federal health care policy.

Results

Of eight changes in federal health care policy, two (introduction of Medicare and Lifetime Health Cover) were directly associated with major changes in the trend lines; however, minor changes in trends were associated with several of the other federal policies. Three types of policy effects were characterised by our model: direction change, magnitude change and inhibition. Results from our model suggest that a policy of Lifetime Health Cover, with a sanction for late adoption of PHI, was immediately successful in changing the private: public mix. The desired effect of the 30% rebate was immediate only in the oldest age group (70+ years), however, introduction of the lifetime health cover and limitations in the model restricted the ability to determine whether or if the rebate had a delayed effect at younger ages.

Conclusion

An outcome-based policy characterisation model is useful in evaluating immediate effects of changes in health care policy.
Chemokine receptors Ccr1, Ccr2, and Ccr5 mediate neutrophil migration to postischemic tissue
Authors: Reichel Christoph A , Khandoga Andrej , Anders Hans-Joachim , Schlöndorff Detlef , Luckow Bruno , Krombach Fritz
Published: November 2005

Leukocyte infiltration of reerfused tissue is a key event in the pathogenesis of ischemia-reperfusion. However, the role of chemokine receptors Ccr1, Ccr2, and Ccr5 for each single step of the postischemic recruitment process of leukocytes has not yet been characterized. Leukocyte rolling, firm adherence, transendothelial, and extravascular migration were analyzed in the cremaster muscle of anaesthetized C57BL/6 mice using near-infrared reflected light oblique transillumination microscopy. Prior to 30 min of ischemia as well as at 5, 30, 60, 90, and 120 min after onset of reperfusion, migration parameters were determined in wild-type, Ccr1−/−, Ccr2−/−, and Ccr5−/− mice. Sham-operated wild-type mice without ischemia were used as controls. No differences were detected in numbers of rolling leukocytes among groups. In contrast, the number of firmly adherent leukocytes was increased significantly in wild-type mice as compared with sham-operated mice throughout the entire reperfusion phase. Already after 5 min of reperfusion, this increase was reduced significantly in Ccr1−/− and Ccr5−/− mice, whereas only in Ccr2−/− mice, was adherence attenuated significantly at 120 min after onset of reperfusion. Furthermore, after 120 min of reperfusion, the number of transmigrated leukocytes (>80% Ly-6G+ neutrophils) was elevated in wild-type mice as compared with sham-operated animals. This elevation was significantly lower in Ccr1−/−, Ccr2−/−, and Ccr5−/− mice. Leukocyte extravascular migration distances were comparable among groups. In conclusion, these in vivo data demonstrate that Ccr1, Ccr2, and Ccr5 mediate the postischemic recruitment of neutrophils through effects on intravascular adherence and subsequent transmigration.
Impaired NADPH oxidase activity in Rac2-deficient murine neutrophils does not result from defective translocation of p47phox and p67phox and can be rescued by exogenous arachidonic acid
Authors: Kim Chaekyun , Dinauer Mary C
Published: November 2005

Rac2 is a hematopoietic-specific Rho-GTPase that plays a stimulus-specific role in regulating reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and other functional responses in neutrophils. In this study, rac2-/- neutrophils were shown to have significantly decreased NADPH oxidase activity and actin remodeling in response to exogenous arachidonic acid (AA), as previously observed for phorbol 12-myristate 13-acetate (PMA) or formyl-Met-Leu-Phe (fMLP) as agonists. PMA-, fMLP-, or AA-induced translocation of p47phox and p67phox to the plasma membrane was not impaired in rac2-- neutrophils. Combined stimulation of rac2-/- neutrophils with exogenous AA and PMA had a synergistic effect on NADPH oxidase activity, and superoxide production increased to a level that was at least as high as wild-type cells and had no effect on fMLP-elicited enzyme activity. Membrane translocation of p47phox and p67phox as well as Rac1 activation was not increased further by combined PMA and AA stimulation. Inhibitor studies were consistent with important roles for phorbol ester-activated protein kinase C (PKC) isoforms and an atypical isoform, PKCζ, in superoxide production by wild-type and rac2-/- neutrophils stimulated with AA and PMA. In addition, PMA-stimulated release of AA and cytoplasmic phospholipase A2 expression in rac2-/- neutrophils were similar to wild-type, suggesting that deficient AA production by PMA-stimulated rac2-/- neutrophils does not explain the effect of exogenous AA on oxidase activity. Although not required for translocation of p47phox and p67phox, Rac2 is necessary for optimal activity of the assembled oxidase complex, an effect that can be replaced by exogenous AA, which may act directly or via an exogenous AA-induced mediator.
Evaluation of toxicity of topiramate exposures reported to poison centers
Authors: Lofton A L , Klein-Schwartz Wendy
Published: November 2005

Published literature on the toxicity of a topiramate overdose is limited to case reports. This retrospective study of poison center data was performed to examine the severity of topiramate overdoses. Data on single substance exposures to topiramate reported to the American Association of Poison Control Centers (AAPCC) Toxic Exposure Surveillance System (TESS) in 2000 and 2001 were retrospectively analysed. A total of 567 cases met the inclusion criteria, of which 39% occurred in adults over 19 years of age and 30.2% in children 5 / 4 years old. The majority of patients (62.1%) experienced no toxicity. The most common clinical effects reported were drowsiness/lethargy (15.5%), dizziness/vertigo (4.9%), agitation (4.9%), confusion (3.9%), nausea (2.6%) and vomiting (2.5%). Symptomatic patients were older than asymptomatic patients and adults were more likely to be managed in a healthcare facility (P B / 0.0001). Patients who received gastrointestinal decontamination experienced less serious outcomes than those without decontamination (P B / 0.02). It is concluded that clinicians should expect relatively mild mental status changes in adults or children with toxicity from topiramate overdose. Serious toxic effects, such as CNS depression with respiratory depression or persistent non-anion gap metabolic acidosis, are infrequent.
Effect of dantrolene on lipid peroxidation, glutathione and glutathione-dependent enzyme activities in experimental otitis media with effusion in guinea pigs
Authors: Ucuncu H , Taysi S , Aktan B , Buyukokuroglu M E , Elmastas M
Published: November 2005

The aims of our study were to assess whether the increased oxidative stress in experimental otitis media with effusion (OME) induced by histamine was reflected in erythrocytes and middle ear effusion fluid by lipid peroxidation; to survey the alterations in antioxidant enzyme activities in experimental OME; and to determine the effect of dantrolene on this oxidative stress. Erythrocyte and middle ear effusion malondialdehyde (MDA) level, erythrocyte glutathione (GSH) and glutathione peroxidase (GSH-Px), glutathione reductase (GRD) and glutathione-S-transferase (GST) activities were measured in three groups of seven guinea pigs, 3 hours after injection of 0.1 mL of histamine (or saline) into the middle ear in guinea pigs with OME (experimental group), in a dantrolene sodium group and in a control group.

Erythrocyte and effusion MDA levels in the dantrolene group were significantly lower than those of the experimental group. Erythrocyte GSH-Px, GST, GRD activities, and GSH levels were significantly higher in the dantrolene group than in the experimental group. Dantrolene sodium decreased the erythrocyte and effusion MDA levels, on the other hand, it increased the GSH and GSH-dependent enzymes.

These findings suggest that reactive oxygen species (ROS) play a role in histamine-induced OME. Pretreatment with dantrolene sodium increases antioxidant enzymes activities and decreases formation of MDA, the indicator of lipid peroxidation, in histamine induced OME.
Discomfort glare from interesting images
Authors: Tuaycharoen N , Tregenza PR
Published: November 2005

In laboratory experiments, subjects viewed bright images projected on to small screens. The projected images ranged from neutral patterns to complex scenes. There was a greater tolerance of discomfort glare from images previously judged ‘interesting’ by an independent subject group than from other screen images giving the same calculated glare rating or from a reference source. When presented with matched pairs, images of natural scenes were reported as less glaring than pictures of urban scenes; specific elements of a view, such as the presence of water, also had an effect.
Fast and accurate simulation of long-term daylight availability using the radiosity method
Authors: Geebelen B , van der Voorden M , Neuckermans H
Published: November 2005

Studies have shown that long-term (e.g., annual or seasonal) predictions of daylight availability which do not take into account the luminance distribution of the sky for each single time-step show considerable differences from long-xterm predictions based on time and direction-dependent luminance distributions. However, with contemporary lighting simulation tools the latter can easily require computation times in the order of days. This paper presents two computation techniques that can be incorporated into any radiosity algorithm and that result in a reduction of computation times to the order of seconds for long-term simulations.
An adaptive neuro-fuzzy model for the prediction and control of light in integrated lighting schemes
Authors: Kurian CP , Kuriachan S , Bhat J , Aithal RS
Published: November 2005

Advanced lighting simulation tools as well as computationally intelligent systems present the possibility of using a model based on computation as a means of controlling lighting on the visual task. Lighting control has now become an essential element of good design and an integral part of energy management programmes. This paper presents a novel computational model suitable for the adaptive predictive control of artificial light in accordance with the variation of daylight. Simulated data and an adaptive neuro-fuzzy inference system are incorporated into the model. The software package Radiance is used to carry out the simulation. In this process, the role of a simulator is considered as the source of the system knowledge by which a supervised learner, implemented in adaptive neuro-fuzzy inference system is trained for faster predictions. The goal of this paper is to make use of the benefits of the hybridization between simulation and machine learning for the purpose of light control.
Utility of Prostate-Specific Antigen Kinetics in Addition to Clinical Factors in the Selection of Patients for Salvage Local Therapy
Authors: Lee Andrew K. , D'Amico Anthony V.
Published: November 2005

A detectable and rising prostate-specific antigen (PSA) level after radical prostatectomy or a rising PSA above the nadir value after radiation therapy may represent a local failure, distant failure, or both. Determining the site or sites of failure is critical for selecting the appropriate salvage therapy. Nevertheless, although PSA failure precedes clinically evident failure by several years, determining the source of the biochemical failure is often not possible using currently available diagnostic studies.

Selecting the optimal therapeutic approach may be guided by the initial clinical factors (eg, T-category, PSA, biopsy Gleason score). If the patient has had a radical prostatectomy, then the pathologic outcomes of the surgery (eg, pathologic T-category and prostatectomy Gleason score, nodal and margin status) may provide further information. Beyond pretreatment clinical and post-treatment pathologic factors, PSA kinetics, and specifically a pretreatment PSA velocity > 2 ng/mL/year, an interval to PSA failure < 3 years and a post-treatment PSA doubling time < 3 months place a man at increased risk for metastases and subsequent prostate cancer–specific mortality, making these men poor candidates for local-only salvage therapy.

Therefore, the optimal candidate for local-only salvage therapy is a man whose pretreatment PSA velocity was 2 ng/mL/year or less, interval to PSA failure exceeds 3 years, and post-treatment PSA doubling time is at least 12 months, and who did not have biopsy or prostatectomy Gleason score of 8 to 10 or seminal vesicle or lymph node involvement.
Pathogenesis and Treatment of Prostate Cancer Bone Metastases: Targeting the Lethal Phenotype
Authors: Loberg Robert D. , Logothetis Christopher J. , Keller Evan T. , Pienta Kenneth J.
Published: November 2005

Traditionally, prostate cancer treatment, as well as all cancer treatment, has been designed to target the tumor cell directly via various hormonal and chemotherapeutic agents. Recently, the realization that cancer cells exist in complex microenvironments that are essential for the tumorigenic and metastatic potential of the cancer cells is starting the redefine the paradigm for cancer therapy. The propensity of prostate cancer cells to metastasize to bone is leading to the design of novel therapies targeting both the cancer cell as well as the bone microenvironment. Tumor cells in the bone interact with the extracellular matrix, stromal cells, osteoblasts, osteoclasts, and endothelial cells to promote tumor-cell survival and proliferation leading to a lethal phenotype that includes increased morbidity and mortality for patients with advanced prostate cancer. Several strategies are being developed that target these complex tumor cell–microenvironment interactions and target the signal transduction pathways of other cells important to the development of metastases, including the osteoclasts, osteoblasts, and endothelial cells of the bone microenvironment. Current and new therapies in metastatic prostate cancer will comprise a multitargeted approach aimed at both the tumor cell and the tumor microenvironment. Here, we review the current therapeutic strategies for targeting the prostate cancer–bone microenvironment and several single- and multiagent targeted approaches to the treatment of advanced prostate cancer that are under development.
Management of Advanced Prostate Cancer After First-Line Chemotherapy
Authors: Berthold Dominik R. , Sternberg Cora N. , Tannock Ian F.
Published: November 2005

Hormone refractory prostate cancer (HRPC) causes substantial morbidity and mortality. There are increasing options for both first- and second-line therapy in the palliative treatment of patients with HRPC. Medications to control symptoms should first be optimized in patients with late-stage disease, and radiotherapy applied to dominant painful bone lesions. Docetaxel, mitoxantrone, satraplatin, and ixabepilone are active chemotherapeutic agents in the first- and/or second-line setting for patients with HRPC, and this may be true also of older drugs such as oral cyclophosphamide and vinorelbine. Radioisotopes such as strontium and samarium are useful for treatment of more generalized bone pain. Third-line hormonal maneuvers including glucocorticoids, ketoconazole, and estrogens can lead to further palliation in some patients, and there are provocative data that chemotherapy might restore hormonal sensitivity in a subset of patients.
Chemotherapy for Hormone-Refractory Prostate Cancer: Now It's a Question of “When?”
Authors: Ryan Charles J. , Eisenberger Mario
Published: November 2005

Recently, data from two randomized phase III studies that compared docetaxel-based chemotherapy to mitoxantrone-based therapy demonstrated that treatment with docetaxel can prolong life in a significant way for patients with hormone-refractory prostate cancer. For many patients who experience disease progression after androgen-deprivation therapy, however, chemotherapy may not be immediately indicated. Such cases include those individuals with hormone-refractory disease in the absence of clinical metastases, and those with asymptomatic metastatic disease, for example. As a result, clinicians treating patients with hormone-refractory disease must weigh the benefits of earlier chemotherapy against its risks, and may consider other therapies such as secondary hormonal approaches before initiating chemotherapy. This decision is further complicated by the fact that a phase III study designed to compare secondary hormonal therapy with chemotherapy has failed due to lack of accrual. Furthermore, the limitations of chemotherapy for prostate cancer are being clarified and include a lack of standard second-line therapy as well as uncertain benefits for those with nonmetastatic disease. In this review, we will highlight some of the issues that impact on the decision of when to start chemotherapy and in whom as well as the potential benefits of secondary hormonal approaches.
Overexpression of the ETS-Related Gene, ERG, Predicts a Worse Outcome in Acute Myeloid Leukemia With Normal Karyotype: A Cancer and Leukemia Group B Study
Authors: Marcucci Guido , Baldus Claudia D. , Ruppert Amy S. , Radmacher Michael D. , Mrózek Krzysztof , Whitman Susan P. , Kolitz Jonathan E. , Edwards Colin G. , Vardiman James W. , Powell Bayard L. , Baer Maria R. , Moore Joseph O. , Perrotti Danilo , Caligiuri Michael A. , Carroll Andrew J. , Larson Richard A. , de la Chapelle Albert , Bloomfield Clara D.
Published: November 2005

Purpose

To test the prognostic significance of ETS-related gene (ERG) expression in cytogenetically normal primary acute myeloid leukemia (AML).

Patients and Methods

Pretreatment blood samples from 84 cytogenetically normal AML patients aged less than 60 years, who were characterized for BAALC expression, FLT3 internal tandem duplication (ITD), and MLL partial tandem duplication (PTD) and uniformly treated on Cancer and Leukemia Group B 9621 protocol, were analyzed for ERG expression by real-time reverse transcriptase polymerase chain reaction. Patients were divided into quartiles according to ERG levels and were compared for clinical outcome. High-density oligonucleotide arrays were used to identify genes differentially expressed between high and low ERG expressers.

Results

With a median follow-up of 5.7 years, patients with the upper 25% of ERG expression values had a worse cumulative incidence of relapse (CIR; P < .001) and overall survival (OS; P = .011) than the remaining patients. In a multivariable analysis, high ERG expression (P < .001) and the presence of MLL PTD (P = .027) predicted worse CIR. With regard to OS, an interaction was observed between expression of ERG and BAALC (P = .013), with ERG overexpression predicting shorter survival only in low BAALC expressers (P = .002). ERG overexpression was an independent prognostic factor even when the unfavorable group of FLT3 ITD patients lacking an FLT3 wild-type allele was included. High ERG expression was associated with upregulation of 112 expressed-sequenced tags and named genes, many of which are involved in cell proliferation, differentiation, and apoptosis.

Conclusion

ERG overexpression in AML patients with normal cytogenetics predicts an adverse clinical outcome and seems to be associated with a specific molecular signature.
Management of Graves’ Disease during Pregnancy: The Key Role of Fetal Thyroid Gland Monitoring
Authors: Luton Dominique , Le Gac Isabelle , Vuillard Edith , Castanet Mireille , Guibourdenche Jean , Noel Michèle , Toubert Marie-Elisabeth , Léger Juliane , Boissinot Christine , Schlageter Marie-Hélène , Garel Catherine , Tébeka Brigitte , Oury Jean-François , Czernichow Paul , Polak Michel
Published: November 2005

Background: Fetuses from mothers with Graves’ disease may experience hypothyroidism or hyperthyroidism due to transplacental transfer of antithyroid drugs (ATD) or anti-TSH receptor antibodies, respectively. Little is known about the fetal consequences. Early diagnosis is essential to successful management. We investigated a new approach to the fetal diagnosis of thyroid dysfunction and validated the usefulness of fetal thyroid ultrasonograms.

Methods: Seventy-two mothers with past or present Graves’ disease and their fetuses were monitored monthly from 22 wk gestation. Fetal thyroid size and Doppler signals, and fetal bone maturation were determined on ultrasonograms, and thyroid function was evaluated at birth. Thyroid function and ATD dosage were monitored in the mothers.

Results: The 31 fetuses whose mothers were anti-TSH receptor antibody negative and took no ATDs during late pregnancy had normal test results. Of the 41 other fetuses, 30 had normal test results at 32 wk, 29 were euthyroid at birth, and one had moderate hypothyroidism on cord blood tests. In the remaining 11 fetuses, goiter was visualized by ultrasonography at 32 wk, and fetal thyroid dysfunction was diagnosed and treated; there was one death, in a late referral, and 10 good outcomes with normal or slightly altered thyroid function at birth. The sensitivity and specificity of fetal thyroid ultrasound at 32 wk for the diagnosis of clinically relevant fetal thyroid dysfunction were 92 and 100%, respectively.

Conclusion: In pregnant women with past or current Graves’ disease, ultrasonography of the fetal thyroid gland by an experienced ultrasonographer is an excellent diagnostic tool. This tool in conjunction with close teamwork among internists, endocrinologists, obstetricians, echographists, and pediatricians can ensure normal fetal thyroid function.
Contractile Activity of Human Decidual Stromal Cells. II. Effect of Interleukin-10
Authors: Kimatrai Maria , Blanco Osmany , Muñoz-Fernández Raquel , Tirado Irene , Martin Francisco , Abadía-Molina Ana Clara , Olivares Enrique G.
Published: November 2005

Context: Human decidual stromal cells (DSC) are myofibroblast-like cells that express α-smooth muscle (α-SM) actin, a protein associated with cell contractility. Several lines of experimental evidence in humans and mice show that antiinflammatory cytokines favor normal pregnancy, whereas Th1 and inflammatory cytokines play a role in abortion. We previously demonstrated that IL-2, a Th1 cytokine, increased the contractility of human DSC.

Objective: We studied the effect of the antiinflammatory cytokines IL-10 and IL-4 on the contractility of DSC from first-trimester pregnancy.

Setting and Patients: We studied 10 healthy women who underwent elective vaginal termination of first-trimester pregnancy at Clínica El Sur, Málaga, and Clínica Ginegranada, Granada.

Main Outcome Measure(s): After isolation of DSC, cell contractility was measured with the collagen gel contraction assay. α-SM actin was detected with Western blotting and immunofluorescence.

Results: We found that IL-10, but not IL-4, increased the volume of the collagen gel matrixes in which the cytokine-treated DSC were cultured, showing that IL-10 decreased DSC contractility. By Western blotting we demonstrated that this effect was not related to an alteration in the synthesis of α-SM actin. Nevertheless, we observed by immunofluorescence microscopy that DSC treated with IL-10 exhibited stress fibers with a lower content of α-SM actin than untreated control DSC.

Conclusions: IL-10 relaxes DSC by reducing the incorporation of α-SM actin into their stress fibers. This relaxing activity may be of relevance for the maintenance of pregnancy.