bluuebunny/crossref_metadata_2025 huggingface dataset:
Enrichment of Genes in the Aortic Intima That Are Associated With Stratified Epithelium
Authors: Young Pampee P. , Modur Vijay , Teleron Amylynn A. , Ladenson Jack H.
Published: May 2005

Background—

Arteries and veins are exposed to different pressures and are easily distinguished by morphology. Although several recent studies have focused on differential gene expression between the arterial and venous endothelium, the molecular distinctions that give rise to the dramatic structural distinctions between arteries and veins, such as in the organization of the intima, are not known.

Methods and Results—

We used high-density oligonucleotide arrays to analyze the transcriptional profile of the mouse aorta and inferior vena cava (IVC), not restricting our analysis to the endothelium, to identify genes whose expression was enriched in aorta over other tissues and the IVC. By quantitative reverse transcription–polymerase chain reaction analysis, these genes have been shown to be highly expressed in the mouse aorta and were either expressed at low levels or were undetectable in the murine IVC. By immunofluorescence analysis of human tissue, we determined that a subset of these aorta-enriched proteins exhibited a primarily intima-restricted expression. Intimal expression of at least a subset of these genes, plakoglobin, galectin 7, sciellin, and SPRR3, was also detected in other types of arteries but not in veins. Furthermore, SPRR3 expression in the intima was primarily associated with atheromas. The proteins identified are functionally related in that they are known to also be enriched in stratified epithelia, where they play an important role in stress-bearing and barrier properties.

Conclusions—

Vascular expression of these genes has not been reported previously. Our observations suggest that they may play a significant role in the mechanisms by which large arteries may adapt to biomechanical stress.
Lower Serum Sodium Is Associated With Increased Short-Term Mortality in Hospitalized Patients With Worsening Heart Failure
Authors: Klein Liviu , O’Connor Christopher M. , Leimberger Jeffrey D. , Gattis-Stough Wendy , Piña Ileana L. , Felker G. Michael , Adams Kirkwood F. , Califf Robert M. , Gheorghiade Mihai
Published: May 2005

Background—

The prognostic value of serum sodium in patients hospitalized for worsening heart failure has not been well defined.

Methods and Results—

The Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) study randomized 949 patients with systolic dysfunction hospitalized for worsening heart failure to receive 48 to 72 hours of intravenous milrinone or placebo in addition to standard therapy. In a retrospective analysis, we investigated the relationship between admission serum sodium and the primary end point of days hospitalized for cardiovascular causes within 60 days of randomization, as well as the secondary end points of in-hospital mortality, 60-day mortality, and 60-day mortality/rehospitalization. The number of days hospitalized for cardiovascular causes was higher in the lowest sodium quartile: 8.0 (4.5, 18.5) versus 6 (4, 13) versus 6 (4, 11.5) versus 6 (4, 12) days (
P
<0.015 for comparison with the lowest quartile). Lower serum sodium was associated with higher in-hospital and 60-day mortality: 5.9% versus 1% versus 2.3% versus 2.3% (
P
<0.015) and 15.9% versus 6.4% versus 7.8% versus 7% (
P
=0.002), respectively. There was a trend toward higher mortality/rehospitalization for patients who were in the lowest sodium quartile. Multivariable-adjusted Cox proportional hazards analysis showed that serum sodium on admission, when modeled linearly, predicted increased 60-day mortality: sodium (per 3-mEq/L decrease) had a hazard ratio of 1.18 with a 95% CI of 1.03 to 1.36 (
P
=0.018).

Conclusions—

In patients hospitalized for worsening heart failure, admission serum sodium is an independent predictor of increased number of days hospitalized for cardiovascular causes and increased mortality within 60 days of discharge.
Functional Role of Phosphodiesterase 3 in Cardiomyocyte Apoptosis
Authors: Ding Bo , Abe Jun-ichi , Wei Heng , Huang Qunhua , Walsh Richard A. , Molina Carlos A. , Zhao Allan , Sadoshima Junichi , Blaxall Burns C. , Berk Bradford C. , Yan Chen
Published: May 2005

Background—

Myocyte apoptosis plays an important role in pathological cardiac remodeling and the progression of heart failure. cAMP signaling is crucial in the regulation of myocyte apoptosis and cardiac remodeling. Multiple cAMP-hydrolyzing phosphodiesterases (PDEs), such as PDE3 and PDE4, coexist in cardiomyocytes and elicit differential temporal/spatial regulation of cAMP signaling. However, the role of PDE3 and PDE4 in the regulation of cardiomyocyte apoptosis remains unclear. Although chronic treatment with PDE3 inhibitors increases mortality in patients with heart failure, the contribution of PDE3 expression/activity in heart failure is not well known.

Methods and Results—

In this study we report that PDE3A expression and activity were significantly reduced in human failing hearts as well as mouse hearts with chronic pressure overload. In primary cultured cardiomyocytes, chronic inhibition of PDE3 but not PDE4 activity by pharmacological agents or adenovirus-delivered antisense PDE3A promoted cardiomyocyte apoptosis. Both angiotensin II (Ang II) and the β-adrenergic receptor agonist isoproterenol selectively induced a sustained downregulation of PDE3A expression and induced cardiomyocyte apoptosis. Restoring PDE3A via adenovirus-delivered expression of wild-type PDE3A1 completely blocked Ang II– and isoproterenol-induced cardiomyocyte apoptosis, suggesting the critical role of PDE3A reduction in cardiomyocyte apoptosis. Moreover, we defined a crucial role for inducible cAMP early repressor expression in PDE3A reduction–mediated cardiomyocyte apoptosis.

Conclusions—

Our results suggest that PDE3A reduction and consequent inducible cAMP early repressor induction are critical events in Ang II– and isoproterenol-induced cardiomyocyte apoptosis and may contribute to the development of heart failure. Drugs that maintain PDE3A function may represent an attractive therapeutic approach to treat heart failure.
Basal NO Locally Modulates Human Iliac Artery Function In Vivo
Authors: Schmitt Matthias , Avolio Albert , Qasem Ahmad , McEniery Carmel M. , Butlin Mark , Wilkinson Ian B. , Cockcroft John R.
Published: May 2005

We demonstrated previously that endogenous NO influences large-artery distensibility in the ovine hindlimb. However, the role of basal NO in larger human conduit arteries is controversial. The aim of this study was to investigate whether basal production of NO, acting locally, influences iliac artery distensibility in humans. Distensibility was assessed by intra-arterial measurement of the pulse wave velocity. Eighteen subjects, free of significant coronary or iliac artery disease, were studied after diagnostic cardiac catheterization. Simultaneous pressure waveforms were recorded with a high-fidelity dual-pressure sensing catheter, placed in the common iliac artery during intra-arterial infusion of saline (baseline), glyceryl trinitrate (4 nmol/min), or
N
G
-monomethyl-
l
-arginine (8 and 16 μmol/min). Drugs were infused proximally, via the catheter to perfuse the segment of artery under study, or distally, via the sheath, to control for any reflex changes in flow or sympathetic activation. Velocity was calculated using the foot-to-foot methodology. Six subjects received glyceryl trinitrate and 12
N
G
-monomethyl-
l
-arginine. There was no change in velocity after infusion of glyceryl trinitrate or
N
G
-monomethyl-
l
-arginine via the sheath. However, infusion of glyceryl trinitrate via the catheter significantly reduced velocity by 31.43±5.80% (mean±SEM;
P
<0.01;
P
=0.02 for comparison). Likewise, infusion of the highest dose of
N
G
-monomethyl-
l
-arginine via the catheter significantly increased velocity by 27.25±8.20% (
P
=0.001;
P
=0.02 for comparison). Importantly, there was no change in mean arterial blood pressure throughout the studies. These data indicate that under resting conditions, local NO production modulates human iliac artery distensibility and that exogenous NO increases arterial distensibility.
Increased Stroke Volume and Aortic Stiffness Contribute to Isolated Systolic Hypertension in Young Adults
Authors: McEniery Carmel M. , Yasmin  , Wallace Sharon , Maki-Petaja Kaisa , McDonnell Barry , Sharman James E. , Retallick Christopher , Franklin Stanley S. , Brown Morris J. , Lloyd R. Catherine , Cockcroft John R. , Wilkinson Ian B.
Published: May 2005

Isolated systolic hypertension is a common condition in individuals aged older than 60 years. However, isolated systolic hypertension has also been described in young individuals, although the mechanisms are poorly understood. We hypothesized that in young adults, isolated systolic hypertension and essential hypertension have different hemodynamic mechanisms and the aim of this study was to test this hypothesis in a cohort of subjects from The ENIGMA Study. Peripheral and central blood pressure, aortic pulse wave velocity, cardiac output, stroke volume, and peripheral vascular resistance were determined in 1008 subjects, aged 17 to 27 years. Compared with normotensive subjects, those with isolated systolic hypertension had significantly higher peripheral, central, and mean blood pressure, aortic pulse wave velocity, cardiac output, and stroke volume (
P
<0.001 for all comparisons). However, there were no differences in pulse pressure amplification, heart rate, or peripheral vascular resistance between the two groups. Compared with subjects with essential hypertension, mean pressure, heart rate, and peripheral vascular resistance were all significantly lower in isolated systolic hypertensive subjects, but pulse pressure amplification, aortic pulse wave velocity, cardiac output, and stroke volume were higher (
P
<0.001 for all comparisons). We have demonstrated that in young adults, isolated systolic hypertension and essential hypertension arise from different hemodynamic mechanisms. Isolated systolic hypertension appears to result from an increased stroke volume and/or aortic stiffness, whereas the major hemodynamic abnormality underlying essential hypertension is an increased peripheral vascular resistance. Long-term follow-up of these individuals is now required to determine whether they are at increased risk compared with age-matched normotensive individuals.
Arterial Elasticity as Part of a Comprehensive Assessment of Cardiovascular Risk and Drug Treatment
Authors: Cohn Jay N. , Duprez Daniel A. , Grandits Gregory A.
Published: May 2005

Early cardiovascular disease can be identified in asymptomatic individuals by noninvasive evaluation of functional and structural abnormalities of the vasculature and heart. These abnomalities are usually a consequence of endothelial dysfunction. A panel of 10 tests, including small and large artery elasticity, has been used as the basis for a screening system that provides a score of 0 to 20 as a guide to the severity of disease. Using that Rasmussen score allows for stratification of patients into low, intermediate, or high risk for progression to cardiovascular morbid events. This comprehensive screening can be performed efficiently in a single room with a single technician. The sensitivity and specificity of this screening system in predicting future cardiovascular events, its superiority to traditional risk factor assessment, and its potential to track the response to therapeutic interventions must be validated in long-term follow-up studies.
Sympatho-Inhibitory Action of Endogenous Adrenomedullin Through Inhibition of Oxidative Stress in the Brain
Authors: Fujita Megumi , Kuwaki Tomoyuki , Ando Katsuyuki , Fujita Toshiro
Published: May 2005

Central sympathetic activation is one of the possible mechanisms underlying hypertension, in which reactive oxygen species may play a role. Thus, we examined whether adrenomedullin, an antioxidant peptide, is involved in the central regulation of arterial pressure through sympatho-modulatory action. Adrenomedullin knockout mice were fed with high-salt diet for 4 weeks to stimulate adrenomedullin production. In the wild-type littermates, brain adrenomedullin content was significantly increased with salt loading, but not in the knockout mice. Intracerebroventricular hyperosmotic saline increased arterial pressure and sympathetic nerve activity in a dose-dependent fashion. With the normal salt diet, the hyperosmotic saline-induced response did not significantly differ between the knockout and wild-type mice; with the high-salt diet, however, the response was significantly greater in the knockout mice than in wild-type littermates (arterial pressure: 35.3±5.7% versus 20.1±2.1%,
P
<0.05; sympathetic nerve activity: 30.3±4.8% versus 15.9±1.5%,
P
<0.05; respectively). Moreover, pretreatment with 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol), a membrane-permeable superoxide dismutase mimetic, inhibited the augmented response to central hyperosmotic saline in salt-loaded knockout mice. Consistently, the hyperosmotic saline-induced production of reactive oxygen species, measured by the lucigenin chemiluminescence method, was significantly greater in the isolated hypothalamus of salt-loaded knockout mice than in that of salt-loaded wild-type ones. In conclusion, endogenous adrenomedullin in the brain may inhibit sympathetic activation through its antioxidant action.
Baroreflex Regulation of Heart Rate and Sympathetic Vasomotor Tone in Women and Men
Authors: Tank Jens , Diedrich Andre , Szczech Elke , Luft Friedrich C. , Jordan Jens
Published: May 2005

Gender has been reported to influence baroreflex heart rate regulation and baroreflex blood pressure buffering. We tested the hypothesis that gender influences baroreflex regulation of heart rate and sympathetic vasomotor tone. We recruited 32 normal-weight healthy subjects (17 men and 15 women). ECGs for heart rate, brachial and finger blood pressure, and muscle sympathetic nerve activity (MSNA) were measured. Baroreflex heart rate and MSNA regulation were assessed using incremental phenylephrine and nitroprusside infusions. Baseline blood pressure was similar in men and women. MSNA was 21±2.5 bursts/min in women and 19±2.8 bursts/min in men (NS). The gain of the baroreflex MSNA curves was similar in women and men (−1.9±0.2 bursts/min per mm Hg in men and −2.0±0.3 bursts/min per mm Hg in women). Baroreflex gain for heart rate regulation was 17±3.2 ms/mm Hg in women and 19±1.9 ms/mm Hg in men (NS). We conclude that baroreflex gains for heart rate and sympathetic MSNA regulation are similar in women and men. However, the probability for congruence between men and women in terms of the MSNA baroreflex curves was 0.06% for burst rate, 0.4% for burst incidence, and 0.01% for burst area. In women, the MSNA baroreflex curve may be shifted to slightly lower blood pressure such that at a given blood pressure MSNA tends to be lower.
The functional significance of buccal feeding in the mouthbrooding cichlid Tropheus moorii
Authors: Schürch Roger , Taborsky Barbara
Published: May 2005

The mouthbrooding cichlid Tropheus moorii exhibits an exceptional degree of maternal investment. Females produce very large eggs, which are incubated for a period of six weeks, and they feed their young in the mouth while starving themselves. Only very few fish species are known to feed their young. We hypothesized that feeding may either (1) benefit females directly if young develop faster, or (2) provide a size advantage to young. To distinguish between these mutually non-exclusive hypotheses, we measured costs and benefits arising for mouthbrooding females when feeding their young. Field observations revealed that mouthbrooding females reduced bite rates, locomotion and territorial defence compared to non-brooding adults. Feeding rates correlated positively with locomotion, as fish moving around more also spent more time with territory defence and other social interactions. This suggests that buccal feeding is costly when compared to mere incubation without feeding the young. In an experiment, in which we controlled the access of females to food, we showed that these costs are apparently not counterbalanced by a benefit to females through a shorter incubation duration. Rather, fed young were larger, heavier and had higher burst-swimming speeds. The extreme maternal investment of T. moorii appears to yield fitness benefits to females by producing larger and stronger young, which consequently should have better survival chances in their natural environment.
Access to Health Services by Canadians Who Are Chronically Ill
Authors: Spenceley Shannon M.
Published: May 2005

Access to health care services in Canada has been identified as an urgent priority, and chronic disease has been suggested as the most pressing health concern facing Canadians. Access to services for Canadians living with chronic disease, however, has received little emphasis in the research literature or in health policy reform documents. A systematic review of research into factors impeding or facilitating access to formal health services for people in Canada living with chronic illness is presented. The review includes 31 studies of Canadian populations published between 1990 and 2002; main results were analyzed for facilitators and barriers to access for people experiencing chronic disease. An underlying organizing construct of symmetry between consumers, providers, and the larger Canadian system is suggested as a relevant lens from which to view the findings. Finally, a discussion of the relationship between identified factors and the principles of primary health care is offered.
Developing a Cultural Model of Caregiving Obligations for Elderly Chinese Wives
Authors: Holroyd Eleanor
Published: May 2005

This article addresses the dilemmas of elderly Chinese women as spousal caregivers in Hong Kong in the 1990s. An in-depth ethnographic approach was used to draw on a convenience sample of 20 elderly wives who were caregivers from Hong Kong. At the conceptual level, the discussion highlights how caregiving is rooted in complex, culturally-based models of contemporary practices, sociohistoric patterns, and gender-specific obligations. The key themes identified were marital duty-bound roles and responsibilities, reciprocity and burden, public guidelines and upholding reputations as Chinese wives, monetary restrictions, affection as an emotional force to sustain caregiving, effects of the caregiving role, and the creation of self-identity through caregiving. The model proposed for interpreting elderly Chinese wives’ caregiving obligations highlights the tension-filled links between Confucianism and government guidelines, early and ongoing socializing experiences, and self-identity.
Modeling ADHD Child and Family Relationships
Authors: Kendall Judy , Leo Michael C. , Perrin Nancy , Hatton Diane
Published: May 2005

Little information is available on how to help families manage common negative sequelae of attention deficit/hyperactivity disorder (ADHD). This article is a report of the extent to which a theoretical formulation of child behavior, maternal distress, and family conflict was explained by data obtained from a community sample of families with children and adolescents with ADHD. Structural equation modeling was used to test the theoretical model. The primary variables of interest were (a) child behavior problems, (b) maternal distress, and (c) family conflict. The results suggest that maternal distress may mediate the relationship between child behavior problems and family conflict, indicating the critical importance of mothers in ADHD families and the need to provide them with additional support.
The influence of high-altitude living on body iron
Authors: Cook James D. , Boy Erick , Flowers Carol , del Carmen Daroca Maria
Published: May 2005

The quantitative assessment of body iron based on measurements of the serum ferritin and transferrin receptor was used to examine iron status in 800 Bolivian mothers and one of their children younger than 5 years. The survey included populations living at altitudes between 156 to 3750 m. Body iron stores in the mothers averaged 3.88 ± 4.31 mg/kg (mean ± 1 SD) and 1.72 ± 4.53 mg/kg in children. No consistent effect of altitude on body iron was detected in children but body iron stores of 2.77 ± 0.70 mg/kg (mean ± 2 standard error [SE]) in women living above 3000 m was reduced by one-third compared with women living at lower altitudes (P < .001). One half of the children younger than 2 years were iron deficient, but iron stores then increased linearly to approach values in their mothers by 4 years of age. When body iron in mothers was compared with that of their children, a striking correlation was observed over the entire spectrum of maternal iron status (r = 0.61, P < .001). This finding could provide the strongest evidence to date of the importance of dietary iron as a determinant of iron status in vulnerable segments of a population. (Blood. 2005;106:1441-1446)
Assessing subgroup effects with binary data: can the use of different effect measures lead to different conclusions?
Authors: White Ian R , Elbourne Diana
Published: May 2005

Background

In order to use the results of a randomised trial, it is necessary to understand whether the overall observed benefit or harm applies to all individuals, or whether some subgroups receive more benefit or harm than others. This decision is commonly guided by a statistical test for interaction. However, with binary outcomes, different effect measures yield different interaction tests. For example, the UK Hip trial explored the impact of ultrasound of infants with suspected hip dysplasia on the occurrence of subsequent hip treatment. Risk ratios were similar between subgroups defined by level of clinical suspicion (P = 0.14), but odds ratios and risk differences differed strongly between subgroups (P < 0.001).

Discussion

Interaction tests on different effect measures differ because they test different null hypotheses. A graphical technique demonstrates that the difference arises when the subgroup risks differ markedly. We consider that the test of interaction acts as a check on the applicability of the trial results to all included subgroups. The test of interaction should therefore be applied to the effect measure which is least likely a priori to exhibit an interaction. We give examples of how this might be done.

The choice of interaction test is especially important when the risk of a binary outcome varies widely between subgroups. The interaction test should be pre-specified and should be guided by clinical knowledge.
General Practitioners' opinions on their practice in mental health and their collaboration with mental health professionals
Authors: Younes Nadia , Gasquet Isabelle , Gaudebout Pierre , Chaillet Marie-Pierre , Kovess Viviane , Falissard Bruno , Hardy Bayle Marie-Christine
Published: May 2005

Background

Common mental health problems are mainly treated in primary care settings and collaboration with mental health services is needed. Prior to re-organisation of the mental health care offer in a geographical area, a study was organized: 1) to evaluate GPs' opinions on their day-to-day practice with Patients with Mental Health Problems (PMHP) and on relationships with Mental Health Professionals (MHPro); 2) to identify factors associated with perceived need for collaboration with MHPro and with actual collaboration.

Methods

All GPs in the South Yvelines area in France (n = 492) were informed of the implementation of a local mental health program. GPs interested in taking part (n = 180) were invited to complete a satisfaction questionnaire on their practice in the field of Mental Health and to include prospectively all PMHP consultants over an 8-day period (n = 1519). For each PMHP, data was collected on demographic and clinical profile, and on needs (met v. unmet) for collaboration with MHPro.

Results

A majority of GPs rated PMHP as requiring more care (83.4%), more time (92.3%), more frequent consultations (64.0%) and as being more difficult to refer (87.7%) than other patients. A minority of GPs had a satisfactory relationship with private psychiatrists (49.5%), public psychiatrists (35%) and social workers (27.8%). 53.9% had a less satisfactory relationship with MHPro than with other physicians.

Needs for collaboration with a MHPro were more often felt in caring for PMHP who were young, not in employment, with mental health problems lasting for more than one year, with a history of psychiatric hospitalization, and showing reluctance to talk of psychological problems and to consult a MHPro.

Needs for collaboration were more often met among PMHP with past psychiatric consultation or hospitalization and when the patient was not reluctant to consult a MHPro. Where needs were not met, GP would opt for the classic procedure of mental health referral for only 31.3% of their PMHP.

Conclusion

GPs need targeted collaboration with MHPro to support their management of PMHP, whom they are willing to care for without systematic referral to specialists as the major therapeutic option.
Perceived barriers for treatment of chronic heart failure in general practice; are they affecting performance?
Authors: Kasje Willeke N , Denig Petra , de Graeff Pieter A , Haaijer-Ruskamp Flora M
Published: May 2005

Background

The aim of this study is to determine to what extent barriers perceived by general practitioners (GPs) for prescribing angiotensin-converting enzyme inhibitors (ACE-I) in chronic heart failure (CHF) patients are related to underuse and underdosing of these drugs in actual practice.

Methods

Barriers were assessed with a semi-structured questionnaire. Prescribing data were extracted from GPs' computerised medical records for a random sample of their CHF patients. Relations between barriers and prescribing behaviour were assessed by means of Spearman rank correlation and multivariate regression modelling.

Results

GPs prescribed ACE-I to 45% of their patients and had previously initiated such treatment in an additional 3.5%, in an average standardised dose of 13.5 mg. They perceived a median of four barriers in prescribing ACE-I or optimising ACE-I dose. Many GPs found it difficult to change treatment initiated by a cardiologist. Furthermore, initiating ACE-I in patients already using a diuretic or stable on their current medication was perceived as barrier. Titrating the ACE-I dose was seen as difficult by more than half of the GPs. No significant relationships could be found between the barriers perceived and actual ACE-I prescribing. Regarding ACE-I dosing, the few GPs who did not agree that the ACE-I should be as high as possible prescribed higher ACE-I doses.

Conclusion

Variation between GPs in prescribing ACE-I for CHF cannot be explained by differences in the barriers they perceive. Tailor-made interventions targeting only those doctors that perceive a specific barrier will therefore not be an efficient approach to improve quality of care.
Optimal search strategies for identifying sound clinical prediction studies in EMBASE
Authors: Holland Jennifer L , Wilczynski Nancy L , Haynes R Brian ,   The Hedges Team
Published: May 2005

Background

Clinical prediction guides assist clinicians by pointing to specific elements of the patient's clinical presentation that should be considered when forming a diagnosis, prognosis or judgment regarding treatment outcome. The numbers of validated clinical prediction guides are growing in the medical literature, but their retrieval from large biomedical databases remains problematic and this presents a barrier to their uptake in medical practice. We undertook the systematic development of search strategies ("hedges") for retrieval of empirically tested clinical prediction guides from EMBASE.

Methods

An analytic survey was conducted, testing the retrieval performance of search strategies run in EMBASE against the gold standard of hand searching, using a sample of all 27,769 articles identified in 55 journals for the 2000 publishing year. All articles were categorized as original studies, review articles, general papers, or case reports. The original and review articles were then tagged as 'pass' or 'fail' for methodologic rigor in the areas of clinical prediction guides and other clinical topics. Search terms that depicted clinical prediction guides were selected from a pool of index terms and text words gathered in house and through request to clinicians, librarians and professional searchers. A total of 36,232 search strategies composed of single and multiple term phrases were trialed for retrieval of clinical prediction studies. The sensitivity, specificity, precision, and accuracy of search strategies were calculated to identify which were the best.

Results

163 clinical prediction studies were identified, of which 69 (42.3%) passed criteria for scientific merit. A 3-term strategy optimized sensitivity at 91.3% and specificity at 90.2%. Higher sensitivity (97.1%) was reached with a different 3-term strategy, but with a 16% drop in specificity. The best measure of specificity (98.8%) was found in a 2-term strategy, but with a considerable fall in sensitivity to 60.9%. All single term strategies performed less well than 2- and 3-term strategies.

Conclusion

The retrieval of sound clinical prediction studies from EMBASE is supported by several search strategies.
Oxidative stress and the use of antioxidants in diabetes: Linking basic science to clinical practice
Authors: Johansen Jeanette Schultz , Harris Alex K , Rychly David J , Ergul Adviye
Published: May 2005

Cardiovascular complications, characterized by endothelial dysfunction and accelerated atherosclerosis, are the leading cause of morbidity and mortality associated with diabetes. There is growing evidence that excess generation of highly reactive free radicals, largely due to hyperglycemia, causes oxidative stress, which further exacerbates the development and progression of diabetes and its complications. Overproduction and/or insufficient removal of these free radicals result in vascular dysfunction, damage to cellular proteins, membrane lipids and nucleic acids. Despite overwhelming evidence on the damaging consequences of oxidative stress and its role in experimental diabetes, large scale clinical trials with classic antioxidants failed to demonstrate any benefit for diabetic patients. As our understanding of the mechanisms of free radical generation evolves, it is becoming clear that rather than merely scavenging reactive radicals, a more comprehensive approach aimed at preventing the generation of these reactive species as well as scavenging may prove more beneficial. Therefore, new strategies with classic as well as new antioxidants should be implemented in the treatment of diabetes.
Weight reduction is not a major reason for improvement in rheumatoid arthritis from lacto-vegetarian, vegan or Mediterranean diets
Authors: Sköldstam Lars , Brudin Lars , Hagfors Linda , Johansson Gunnar
Published: May 2005

Objectives

Several investigators have reported that clinical improvements of patients with rheumatoid arthritis (RA), from participating in therapeutic diet intervention studies, have been accompanied by loss of body weight. This has raised the question whether weight reduction per se can improve RA. In order to test this hypothesis, three previously conducted diet intervention studies, comprising 95 patients with RA, were pooled. Together with Age, Gender, and Disease Duration, change during the test period in body weight, characterised dichotomously as reduction or no reduction (dichoΔBody Weight), as well as Diet (dichotomously as ordinary diet or test diet), were the independent variables. Dependent variables were the difference (Δ) from baseline to conclusion of the study in five different disease outcome measures. ΔESR and ΔPain Score were both characterised numerically and dichotomously (improvement or no improvement). ΔAcute Phase Response, ΔPhysical Function, and ΔTender Joint Count were characterised dichotomously only. Multiple logistic regression was used to analyse associations between the independent and the disease outcome variables.

Results

Statistically significant correlations were found between Diet and three disease outcome variables i.e. ΔAcute-Phase Response, ΔPain Score, and ΔPhysical Function. Δ Body Weight was univariately only correlated to ΔAcute-Phase Response but not significant when diet was taken into account.

Conclusion

Body weight reduction did not significantly contribute to the improvement in rheumatoid arthritis when eating lacto-vegetarian, vegan or Mediterranean diets.
Maternal mortality in the rural Gambia, a qualitative study on access to emergency obstetric care
Authors: Cham Mamady , Sundby Johanne , Vangen Siri
Published: May 2005

Background

Maternal mortality is the vital indicator with the greatest disparity between developed and developing countries. The challenging nature of measuring maternal mortality has made it necessary to perform an action-oriented means of gathering information on where, how and why deaths are occurring; what kinds of action are needed and have been taken. A maternal death review is an in-depth investigation of the causes and circumstances surrounding maternal deaths. The objectives of the present study were to describe the socio-cultural and health service factors associated with maternal deaths in rural Gambia.

Methods

We reviewed the cases of 42 maternal deaths of women who actually tried to reach or have reached health care services. A verbal autopsy technique was applied for 32 of the cases. Key people who had witnessed any stage during the process leading to death were interviewed. Health care staff who participated in the provision of care to the deceased was also interviewed. All interviews were tape recorded and analyzed by using a grounded theory approach. The standard WHO definition of maternal deaths was used.

Results

The length of time in delay within each phase of the model was estimated from the moment the woman, her family or health care providers realized that there was a complication until the decision to seeking or implementing care was made. The following items evolved as important: underestimation of the severity of the complication, bad experience with the health care system, delay in reaching an appropriate medical facility, lack of transportation, prolonged transportation, seeking care at more than one medical facility and delay in receiving prompt and appropriate care after reaching the hospital.

Conclusion

Women do seek access to care for obstetric emergencies, but because of a variety of problems encountered, appropriate care is often delayed. Disorganized health care with lack of prompt response to emergencies is a major factor contributing to a continued high mortality rate.
Preventive and curative effect of melatonin on mammary carcinogenesis induced by dimethylbenz[a]anthracene in the female Sprague–Dawley rat
Authors: Lenoir Véronique , Yon de Jonage-Canonico Marianne Beau , Perrin Marie-Hélène , Martin Antoine , Scholler Robert , Kerdelhué Bernard
Published: May 2005

Introduction

It has been well documented that the pineal hormone, melatonin, which plays a major role in the control of reproduction in mammals, also plays a role in the incidence and growth of breast and mammary cancer. The curative effect of melatonin on the growth of dimethylbenz [a]anthracene-induced (DMBA-induced) mammary adenocarcinoma (ADK) has been previously well documented in the female Sprague–Dawley rat. However, the preventive effect of melatonin in limiting the frequency of cancer initiation has not been well documented.

Methods

The aim of this study was to compare the potency of melatonin to limit the frequency of mammary cancer initiation with its potency to inhibit tumor progression once initiation, at 55 days of age, was achieved. The present study compared the effect of preventive treatment with melatonin (10 mg/kg daily) administered for only 15 days before the administration of DMBA with the effect of long-term (6-month) curative treatment with the same dose of melatonin starting the day after DMBA administration. The rats were followed up for a year after the administration of the DMBA.

Results

The results clearly showed almost identical preventive and curative effects of melatonin on the growth of DMBA-induced mammary ADK. Many hypotheses have been proposed to explain the inhibitory effects of melatonin. However, the mechanisms responsible for its strong preventive effect are still a matter of debate. At least, it can be envisaged that the artificial amplification of the intensity of the circadian rhythm of melatonin could markedly reduce the DNA damage provoked by DMBA and therefore the frequency of cancer initiation.

Conclusion

In view of the present results, obtained in the female Sprague–Dawley rat, it can be envisaged that the long-term inhibition of mammary ADK promotion by a brief, preventive treatment with melatonin could also reduce the risk of breast cancer induced in women by unidentified environmental factors.
The Sequence Ontology: a tool for the unification of genome annotations
Authors: Eilbeck Karen , Lewis Suzanna E , Mungall Christopher J , Yandell Mark , Stein Lincoln , Durbin Richard , Ashburner Michael
Published: May 2005

The Sequence Ontology (SO) is a structured controlled vocabulary for the parts of a genomic annotation. SO provides a common set of terms and definitions that will facilitate the exchange, analysis and management of genomic data. Because SO treats part-whole relationships rigorously, data described with it can become substrates for automated reasoning, and instances of sequence features described by the SO can be subjected to a group of logical operations termed extensional mereology operators.
Long-Term Results of the R-CHOP Study in the Treatment of Elderly Patients With Diffuse Large B-Cell Lymphoma: A Study by the Groupe d'Etude des Lymphomes de l'Adulte
Authors: Feugier P. , Van Hoof A. , Sebban C. , Solal-Celigny P. , Bouabdallah R. , Fermé C. , Christian B. , Lepage E. , Tilly H. , Morschhauser F. , Gaulard P. , Salles G. , Bosly A. , Gisselbrecht C. , Reyes F. , Coiffier B.
Published: May 2005

Purpose

To analyze the long-term outcome of patients included in the Lymphome Non Hodgkinien study 98-5 (LNH98-5) comparing cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) to rituximab plus CHOP (R-CHOP) in elderly patients with diffuse large B-cell lymphoma.

Patients and Methods

LNH98-5 was a randomized study that included 399 previously untreated patients, age 60 to 80 years, with diffuse large B-cell lymphoma. Patients received eight cycles of classical CHOP (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, and prednisone 40 mg/m2 for 5 days) every 3 weeks. In R-CHOP, rituximab 375 mg/m2 was administered the same day as CHOP. Survivals were analyzed using the intent-to-treat principle.

Results

Median follow-up is 5 years at present. Event-free survival, progression-free survival, disease-free survival, and overall survival remain statistically significant in favor of the combination of R-CHOP (P = .00002, P < .00001, P < .00031, and P < .0073, respectively, in the log-rank test). Patients with low-risk or high-risk lymphoma according to the age-adjusted International Prognostic Index have longer survivals if treated with the combination. No long-term toxicity appeared to be associated with the R-CHOP combination.

Conclusion

Using the combination of R-CHOP leads to significant improvement of the outcome of elderly patients with diffuse large B-cell lymphoma, with significant survival benefit maintained during a 5-year follow-up. This combination should become the standard for treating these patients.
Inactivation of the Lamin A/C Gene by CpG Island Promoter Hypermethylation in Hematologic Malignancies, and Its Association With Poor Survival in Nodal Diffuse Large B-Cell Lymphoma
Authors: Agrelo Ruben , Setien Fernando , Espada Jesus , Artiga Maria Jesus , Rodriguez Maria , Pérez-Rosado Alberto , Sanchez-Aguilera Abel , Fraga Mario F. , Piris Miguel Angel , Esteller Manel
Published: May 2005

Purpose

Lamins support the nuclear envelope and provide anchorage sites for chromatin, but they are also involved in DNA synthesis, transcription, and apoptosis. Although the lack of expression of A-type lamins in lymphoma and leukemia has been reported, the mechanism was unknown. We investigated the possible role of CpG island hypermethylation in lamin A/C silencing and its prognostic relevance.

Patients and Methods

The promoter CpG island methylation status of the lamin A/C gene, encoding the A-type lamins, was analyzed by bisulfite genomic sequencing and methylation-specific polymerase chain reaction in human cancer cell lines (n = 74; from 17 tumor types), and primary leukemias (n = 60) and lymphomas (n = 80). Lamin A/C expression was determined by reverse-transcription polymerase chain reaction, Western blot, immunohistochemistry, and immunofluorescence.

Results

Lamin A/C promoter CpG island methylation was found in hematologic malignancies: seven (50%) of 14 leukemia- and five (42%) of 13 lymphoma cell lines. The presence of hypermethylation was associated with the loss of gene expression while a demethylating agent restored expression. In primary malignancies, lamin A/C hypermethylation was present in 18% (nine of 50) of acute lymphoblastic leukemias and 34% (14 of 41) of nodal diffuse large B-cell lymphomas. The presence of lamin A/C hypermethylation in nodal diffuse large B-cell lymphomas correlated strongly with a decrease in failure-free survival (Kaplan-Meier, P = .0001) and overall survival (Kaplan-Meier, P = .0005).

Conclusion

Epigenetic silencing of the lamin A/C gene by CpG island promoter hypermethylation is responsible for the loss of expression of A-type lamins in leukemias and lymphomas. The finding that lamin A/C hypermethylation is associated with poor outcome in diffuse large B-cell lymphomas suggests important clinical implications.
A Dual Group Processes Model of Individual Differences in Prejudice
Authors: Kreindler Sara A.
Published: May 2005

The study of right-wing authoritarianism (RWA) and Social Dominance Orientation (SDO) as predictors of prejudice has represented an attempt to explain group dynamics in terms of individual traits. In contrast, I argue that the individual tendencies that predict prejudice are actually a product of group dynamics. This article critiques personality approaches, focusing primarily on authoritarianism and secondarily on social dominance, and defends a model that explains the 2 variables in terms of discrete group processes. According to the Dual Group Processes model, SDO reflects category differentiation, which involves the evaluation of individuals on the basis of their category membership. RWA reflects normative differentiation, which involves the evaluation of ingroup members on the basis of their prototypicality. Authoritarian aggression—whether against ethnic minorities or other targets—is conceptualized as an intragroup phenomenon, involving the rejection of perceived antinorm deviants who threaten the longevity or legitimacy of social norms.
Rethinking the Link Between Categorization and Prejudice Within the Social Cognition Perspective
Authors: Park Bernadette , Judd Charles M.
Published: May 2005

For the past 40 years, social psychological research on stereotyping and prejudice in the United States has been dominated by the social cognition perspective, which has emphasized the important role of basic categorization processes in intergroup dynamics. An inadvertent consequence of this approach has been a disproportionate focus on social categorization as a causal factor in intergroup animosity and, accordingly, an emphasis on approaches that minimize category distinctions as the solution to intergroup conflict. Though recognizing the crucial function of categorization, we question existing support for the hypothesis that the perception of strong group differences necessarily results in greater intergroup bias. Given that it is neither feasible nor ultimately desirable to imagine that social categories can be eliminated, we suggest that a more useful approach is one that promotes intergroup harmony even while recognizing and valuing the distinctions that define our social world.
Teacher Expectations and Self-Fulfilling Prophecies: Knowns and Unknowns, Resolved and Unresolved Controversies
Authors: Jussim Lee , Harber Kent D.
Published: May 2005

This article shows that 35 years of empirical research on teacher expectations justifies the following conclusions: (a) Self-fulfilling prophecies in the classroom do occur, but these effects are typically small, they do not accumulate greatly across perceivers or over time, and they may be more likely to dissipate than accumulate; (b) powerful self-fulfilling prophecies may selectively occur among students from stigmatized social groups; (c) whether self-fulfilling prophecies affect intelligence, and whether they in general do more harm than good, remains unclear, and (d) teacher expectations may predict student outcomes more because these expectations are accurate than because they are self-fulfilling. Implications for future research, the role of self-fulfilling prophecies in social problems, and perspectives emphasizing the power of erroneous beliefs to create social reality are discussed.
W(h)ither the Deaf Community? Population, Genetics, and the Future of Australian Sign Language
Authors: Johnston Trevor A
Published: May 2005

According to enrollments in schools for the deaf and data from the
national census and neonatal hearing screening programs, the incidence
of severe and profound childhood deafness in Australia is, and has been,
less than commonly assumed. Factors implicated include improved medical
care, mainstreaming, cochlear implants, and genetic science. Data for
the United States, Britain, and other developed countries seem consistent
with those for Australia. Declining prevalence and incidence rates have
immediate implications for sign-based education, teacher-of-the-deaf
training programs, and educational interpreting. There are also serious
consequences for research, documentation, and teaching regarding
Australian Sign Language (Auslan), and for the future viability of
Auslan. Prompt action is essential if a credible corpus of Auslan is to
be collected as the basis for a valid and verifiable description of one
of the few native sign languages in the world with significant attested
historical depth.
Deaf Signers Who Know Japanese Remember Words and Numbers More Effectively Than Deaf Signers Who Know English
Authors: Flaherty Mary , Moran Aidan P
Published: May 2005

Deaf people have difficulty reading and remembering English script because of its sound-based orthography. Logographs (e.g., kanji, Arabic numerals) should not pose the same challenge because they are based on meaning, not sound. Little research has been conducted to test this theory's validity cross-culturally. The present study was an attempt to do just that. The first of two experiments tested immediate memory spans for word sequences of 20 hearing Irish, 20 prelingually deaf Americans, 20 hearing Japanese, and 20 prelingually deaf Japanese. For English words, deaf participants showed shorter memory spans than hearing participants, but memory spans were similar for deaf and hearing participants for words in kanji, the logographic system for Japanese writing. The second experiment tested memory span for Arabic numerals, with the same participants. Deaf English-readers showed shorter memory spans than their hearing counterparts, but deaf and hearing Japanese performed similarly.