bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct Pathways Regulate Expression of Cardiac Electrical and Mechanical Junction Proteins in Response to Stretch
Authors: Yamada Kiyomi , Green Karen G. , Samarel Allen M. , Saffitz Jeffrey E.
Published: July 2005

To define mechanisms regulating expression of cell–cell junction proteins, we have developed an in vitro system in which neonatal rat ventricular myocytes were subjected to pulsatile stretch. Previously, we showed that expression of the gap junction protein, connexin (Cx) 43, is increased by ≈2-fold after 1 hour of stretch, and this response is mediated by stretch-induced secretion of vascular endothelial growth factor (VEGF). Here, we report that the mechanical junction proteins plakoglobin, desmoplakin, and N-cadherin are also upregulated by pulsatile stretch but by a mechanism independent of VEGF or other secreted chemical signals. Stretch-induced upregulation of mechanical junction proteins was blocked by anti–β
1
and anti–β
3
integrin antibodies. Transfection of cells with adenovirus expressing GFP-FRNK, a dominant-negative inhibitor of focal adhesion kinase (FAK)-dependent signaling, blocked stretch-induced upregulation of Cx43 and mechanical junction proteins but did not block the ability of exogenous VEGF to upregulate Cx43 expression. Conditioned medium removed from uninfected cells after stretch increased Cx43 expression when added to nonstretched cells, and this effect was blocked by anti-VEGF antibodies, but stretch-conditioned medium from GFP-FRNK cells had no effect on Cx43 expression. The src kinase inhibitor 4-amino-5-(4-chloro-phenyl)-7-(
t
-butyl)pyrazolol[3,4-
d
]pyrimidine blocked stretch-induced upregulation of mechanical junction proteins but not Cx43. Thus, stretch upregulates expression of both electrical and mechanical junction proteins via integrin-dependent activation of FAK. Stretch-induced upregulation of Cx43 expression is mediated by FAK-dependent secretion of VEGF. In contrast, stretch-induced upregulation of adhesion junction proteins involves intracellular mechanotransduction pathways initiated via integrin signaling and acting downstream of src kinase.
Ambulatory Transcranial Doppler Cerebral Embolic Signal Detection in Symptomatic and Asymptomatic Carotid Stenosis
Authors: Mackinnon Andrew D. , Aaslid Rune , Markus Hugh S.
Published: July 2005

Background and Purpose—

Transcranial Doppler (TCD) ultrasound can detect asymptomatic emboli in carotid stenosis. Current systems are nonportable and can only record for short durations. A novel ambulatory TCD system allows prolonged recording. We applied this to patients with symptomatic and asymptomatic carotid stenosis to determine patterns of embolization in the 2 conditions and optimal recording protocols.

Methods—

Ambulatory TCD recordings were performed in 12 symptomatic and 15 asymptomatic carotid stenosis (≥50%) patients for 8 hours and then repeated on a second occasion.

Results—

Nine (75%) of symptomatic subjects had embolic signals during the first recording. In this group, repeating the recording did not increase the proportion of positive patients. In asymptomatic patients, 4 (26.7%) had embolic signals on 1 recording, and this proportion increased to 46.7% after 2 recordings. There was significant clustering of embolic signals demonstrating that the process was nonrandom.

Conclusions—

Ambulatory TCD is possible in patients with carotid artery stenosis. By increasing the duration of recording, additional information is provided, particularly in asymptomatic patients. Our results also demonstrate clustering of embolic signals. Our study provides baseline data to allow studies in both asymptomatic and symptomatic carotid stenosis to be planned.
Interaction Between a Rat Model of Cerebral Ischemia and β-Amyloid Toxicity
Authors: Whitehead Shawn , Cheng Guanliang , Hachinski Vladimir , Cechetto David F.
Published: July 2005

Background and Purpose—

Clinical data suggest that Alzheimer disease (AD) and stroke together potentiate cognitive impairment. Our rat model demonstrates that this interaction may be mediated through inflammatory cells and pathways. Thus, anti-inflammatory agents such as Triflusal, a nonsteroidal anti-inflammatory agent (NSAID), may provide neuroprotection for susceptible neurons in AD and cerebral ischemia.

Methods—

AD was modeled by cerebroventricular injections of β-amyloid (Aβ25–35) and subcortical lacunar infarcts by striatal endothelin injections. Inflammatory mechanisms were examined by immunohistochemical analysis. Behavioral tasks were assessed with the Montoya staircase test.

Results—

Triflusal reduced pathologic and inflammatory markers and functional deficits in rats receiving Aβ or endothelin alone but was less effective in the more severe pathology of the combined Aβ/endothelin model.

Conclusions—

Higher doses or more prolonged treatment with NSAIDs may be required for more effective neuroprotection in combined AD and stroke conditions.
Transesophageal Echocardiography
Authors: Brickner M. Elizabeth
Published: July 2005

Transesophageal echocardiography (TEE) has become a widely used imaging modality that provides important and complementary information to standard transthoracic imaging. Sonographic imaging of the heart is performed using a flexible endoscope with an ultrasound transducer mounted near the end. The close proximity of the heart to the esophagus allows the use of a high-frequency transducer, which gives high-quality images of cardiac structure and avoids interference from air-containing lungs. TEE allows high-quality imaging of most cardiac structures, including posterior structures such as the atria and their appendages as well as the thoracic aorta. However, anterior structures such as the true left ventricular apex and the pulmonic valve may be better imaged from the transthoracic position. While there are many indications for TEE, the most common indications are to rule out endocarditis or, in the clinical situation of stroke, to rule out cardiac-source emboli.
The Accuracy of Sonography in Detecting Abnormal Axillary Lymph Nodes When Breast Cancer Is Present
Authors: Mobbs Louise M. , Jannicky Elisabeth A. S. , Weaver Donald L. , Harvey Susan C.
Published: July 2005

This study evaluated the accuracy of sonography in detecting abnormal ipsilateral axillary lymph nodes in women with breast cancer. The authors retrospectively reviewed the sonographic findings and surgical pathology reports of 71 women who were diagnosed with breast cancer by ultrasound-guided biopsies. Results found in 71 cases that the sonographic specificity was 82%, whereas the sensitivity was only 40%. In 8 of the 17 cases (47%), sonography was suspicious for cancer, and the final surgical pathology was malignant. In 42 of 54 cases (77%), sonography of the axilla was not suspicious, and the final axillary node surgical pathology was negative. In 12 cases, sonographic images of the lymph nodes appeared normal, whereas the surgical pathology of the axillary nodes demonstrated malignancy. Ultrasound imaging has a high specificity when evaluating axillary lymph nodes and can be recommended when a suspicious finding is detected in the breast during diagnostic breast sonographic examination.
Diffuse Neonatal Hemangiomatosis
Authors: Upton Audra
Published: July 2005

Multiple cutaneous hemangiomas of the skin have commonly been recognized as a marker to potentially life-threatening visceral hemangiomas. When cutaneous hemanigomas coexist with visceral hemangiomas, a rare condition known as diffuse neonatal hemangiomatosis is formed. Hemangiomas appear to form sporadically. Sonography is the initial imaging modality of choice. The advantages of sonography are that it is noninvasive, portable, and less expensive. An infant girl presented at 1 week of age with three cutaneous hemangiomas located on her left cheek, shoulder, and chest. A routine sonogram of the patient’s liver demonstrated several well-marginated, hypoechoic lesions within the liver. The pediatrician was notified, and a series of biweekly sonograms and steroid therapy were started. In this case, steroid therapy was successful, and the patient currently has no problems with hemangiomas.
Neutrophil stimulation with Mycobacterium bovis bacillus Calmette-Guérin (BCG) results in the release of functional soluble TRAIL/Apo-2L
Authors: Kemp Troy J. , Ludwig Aaron T. , Earel James K. , Moore Jill M. , VanOosten Rebecca L. , Moses Bonita , Leidal Kevin , Nauseef William M. , Griffith Thomas S.
Published: July 2005

Mycobacterium bovis bacillus Calmette-Guérin (BCG) has been used to treat bladder cancer for almost 30 years; however, the effector mechanism of the BCG-induced antitumor response remains enigmatic. Most BCG research has focused on the mononuclear-cell infiltrate, but growing evidence supports a role for neutrophils in the antitumor response. Previously, we demonstrated increased urinary tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL/Apo-2L) levels from BCG-responsive patients compared to nonresponders. Interestingly, neutrophils isolated from the urine expressed TRAIL/Apo-2L, leading us to investigate the neutrophil response to BCG. BCG-stimulated neutrophils expressed surface-bound and released functional soluble TRAIL/Apo-2L. Whereas neither interferon α (IFN-α) nor IFN-γ directly induced TRAIL/Apo2L expression by neutrophils, IFN-α did stimulate TRAIL gene transcription, and IFN-primed neutrophils contained and released more TRAIL/Apo-2L after BCG stimulation than did unprimed neutrophils. In unstimulated neutrophils TRAIL/Apo-2L was present predominantly in the azurophilic granules and plasma-membrane–enriched/secretory-granule fraction. Finally, we observed that killed BCG, Toll-like receptor 2 (TLR2) and TLR4 agonists, and an M tuberculosis cell-wall fraction were each capable of inducing the release of soluble TRAIL/Apo-2L from neutrophils. These results further characterize the potential role neutrophils may play in initiating the antitumor response described with BCG treatment for superficial bladder cancer.
Induction of HM1.24 peptide–specific cytotoxic T lymphocytes by using peripheral-blood stem-cell harvests in patients with multiple myeloma
Authors: Jalili Ali , Ozaki Shuji , Hara Tomoko , Shibata Hironobu , Hashimoto Toshihiro , Abe Masahiro , Nishioka Yasuhiko , Matsumoto Toshio
Published: July 2005

HM1.24 antigen is preferentially overexpressed in multiple myeloma (MM) cells but not in normal cells. To explore the potential of HM1.24 as a target for cellular immunotherapy, we selected 4 HM1.24-derived peptides that possess binding motifs for HLA-A2 or HLA-A24 by using 2 computer-based algorithms. The ability of these peptides to generate cytotoxic T lymphocytes (CTLs) was examined in 20 healthy donors and 6 patients with MM by a reverse immunologic approach. Dendritic cells (DCs) were induced from peripheral-blood mononuclear cells of healthy donors or peripheral-blood stem-cell (PBSC) harvests from patients with MM, and autologous CD8+ T cells were stimulated with HM1.24 peptide–pulsed DCs. Both interferon-γ–producing and cytotoxic responses were observed after stimulation with either HM1.24-126 or HM1.24-165 peptides in HLA-A2 or HLA-A24 individuals. The peptide-specific recognition of these CTLs was further confirmed by tetramer assay and cold target inhibition assay. Importantly, HM1.24-specific CTLs were also induced from PBSC harvests from patients with MM and these CTLs were able to kill MM cells in an HLA-restricted manner. These results indicate the existence of functional DCs and HM1.24-specific CTL precursors within PBSC harvests and provide the basis for cellular immunotherapy in combination with autologous PBSC transplantation in MM.
JAK2 mutation 1849G>T is rare in acute leukemias but can be found in CMML, Philadelphia chromosome–negative CML, and megakaryocytic leukemia
Authors: Jelinek Jaroslav , Oki Yasuhiro , Gharibyan Vazganush , Bueso-Ramos Carlos , Prchal Josef T. , Verstovsek Srdan , Beran Miloslav , Estey Elihu , Kantarjian Hagop M. , Issa Jean-Pierre J.
Published: July 2005

An activating 1849G>T mutation of JAK2 (Janus kinase 2) tyrosine kinase was recently described in chronic myeloproliferative disorders (MPDs). Its role in other hematologic neoplasms is unclear. We developed a quantitative pyrosequencing assay and analyzed 374 samples of hematologic neoplasms. The mutation was frequent in polycythemia vera (PV) (86%) and myelofibrosis (95%) but less prevalent in acute myeloid leukemia (AML) with an antecedent PV or myelofibrosis (5 [36%] of 14 patients). JAK2 mutation was also detected in 3 (19%) of 16 patients with Philadelphia-chromosome (Ph)–negative chronic myelogenous leukemia (CML), 2 (18%) of 11 patients with megakaryocytic AML, 7 (13%) of 52 patients with chronic myelomonocytic leukemia, and 1 (1%) of 68 patients with myelodysplastic syndromes. No mutation was found in Ph+CML (99 patients), AML M0-M6 (28 patients), or acute lymphoblastic leukemia (20 patients). We conclude that the JAK2 1849G>T mutation is common in Ph– MPD but not critical for transformation to the acute phase of these diseases and that it is generally rare in aggressive leukemias.
Cigarette smoke induces IL-8, but inhibits eotaxin and RANTES release from airway smooth muscle
Authors: Oltmanns Ute , Chung Kian F , Walters Matthew , John Matthias , Mitchell Jane A
Published: July 2005

Background

Cigarette smoke is the leading risk factor for the development of chronic obstructive pulmonary disease (COPD) an inflammatory condition characterised by neutrophilic inflammation and release of proinflammatory mediators such as interleukin-8 (IL-8). Human airway smooth muscle cells (HASMC) are a source of proinflammatory cytokines and chemokines. We investigated whether cigarette smoke could directly induce the release of chemokines from HASMC.

Methods

HASMC in primary culture were exposed to cigarette smoke extract (CSE) with or without TNFα. Chemokines were measured by enzyme-linked immunosorbent assay (ELISA) and gene expression by real time polymerase chain reaction (PCR). Data were analysed using one-way analysis of variance (ANOVA) followed by Bonferroni's t test

Results

CSE (5, 10 and 15%) induced IL-8 release and expression without effect on eotaxin or RANTES release. At 20%, there was less IL-8 release. TNFα enhanced CSE-induced IL-8 release and expression. However, CSE (5–30%) inhibited TNFα-induced eotaxin and RANTES production. The effects of CSE on IL-8 release were inhibited by glutathione (GSH) and associated with the induction of the oxidant sensing protein, heme oxygenase-1.

Conclusion

Cigarette smoke may directly cause the release of IL-8 from HASMC, an effect enhanced by TNF-α which is overexpressed in COPD. Inhibition of eotaxin and RANTES by cigarette smoke is consistent with the predominant neutrophilic but not eosinophilic inflammation found in COPD.
CCR2 and CXCR3 agonistic chemokines are differently expressed and regulated in human alveolar epithelial cells type II
Authors: Pechkovsky Dmitri V , Goldmann Torsten , Ludwig Corinna , Prasse Antje , Vollmer Ekkehard , Müller-Quernheim Joachim , Zissel Gernot
Published: July 2005

The attraction of leukocytes from circulation to inflamed lungs depends on the activation of both the leukocytes and the resident cells within the lung. In this study we determined gene expression and secretion patterns for monocyte chemoattractant protein-1 (MCP-1/CCL2) and T-cell specific CXCR3 agonistic chemokines (Mig/CXCL9, IP-10/CXCL10, and I-TAC/CXCL11) in TNF-α-, IFN-γ-, and IL-1β-stimulated human alveolar epithelial cells type II (AEC-II). AEC-II constitutively expressed high level of CCL2 mRNAin vitroandin situ, and released CCL2 proteinin vitro. Treatment of AEC-II with proinflammatory cytokines up-regulated both CCL2 mRNA expression and release of immunoreactive CCL2, whereas IFN-γ had no effect on CCL2 release. In contrast, CXCR3 agonistic chemokines were not detected in freshly isolated AEC-II or in non-stimulated epithelial like cell line A549. IFN-γ, alone or in combination with IL-1β and TNF-α resulted in an increase in CXCL10, CXCL11, and CXCL9 mRNA expression and generation of CXCL10 protein by AEC-II or A549 cells. CXCL10 gene expression and secretion were induced in dose-dependent manner after cytokine-stimulation of AEC-II with an order of potency IFN-γ>>IL-1β ≥ TNF-α. Additionally, we localized the CCL2 and CXCL10 mRNAs in human lung tissue explants byin situhybridization, and demonstrated the selective effects of cytokines and dexamethasone on CCL2 and CXCL10 expression. These data suggest that the regulation of the CCL2 and CXCL10 expression exhibit significant differences in their mechanisms, and also demonstrate that the alveolar epithelium contributes to the cytokine milieu of the lung, with the ability to respond to locally generated cytokines and to produce potent mediators of the local inflammatory response.
Vector analysis as a fast and easy method to compare gene expression responses between different experimental backgrounds
Authors: Breitling Rainer , Armengaud Patrick , Amtmann Anna
Published: July 2005

Background

Gene expression studies increasingly compare expression responses between different experimental backgrounds (genetic, physiological, or phylogenetic). By focusing on dynamic responses rather than a direct comparison of static expression levels, this type of study allows a finer dissection of primary and secondary regulatory effects in the various backgrounds. Usually, results of such experiments are presented in the form of Venn diagrams, which are intuitive and visually appealing, but lack a statistical foundation.

Results

Here we introduce Vector Analysis (VA) as a simple, yet principled, approach to comparing expression responses in different experimental backgrounds. VA enables the automatic assignment of genes to response prototypes and provides statistical significance estimates to eliminate spurious response patterns. The application of VA to a real dataset, comparing nutrient starvation responses in wild type and mutant Arabidopsis plants, reveals that consistent patterns of expression behavior are present in the data and are reliably detected by the algorithm.

Conclusion

Vector analysis is a flexible, easy-to-use technique to compare gene expression patterns in different experimental backgrounds. It compares favorably with the classical Venn diagram approach and can be implemented manually using spreadsheets, such as Excel, or automatically by using the supplied software.
Regulation of the Pax6 : Pax6(5a) mRNA ratio in the developing mammalian brain
Authors: Pinson Jeni , Mason John O , Simpson T Ian , Price David J
Published: July 2005

Background

Early in mammalian brain development cell proliferation generates a population of progenitor cells whose subsequent divisions produce increasing numbers of postmitotic neurons. Pax6 affects both processes and it has been suggested that this changing role is due at least in part to changes in the relative concentrations of its two main isoforms, (i) Pax6 and (ii) Pax6(5a), created by insertion of a 42 bp exon (exon 5a) into one of the two DNA-binding domains. Crucially, however, no previous study has determined whether the ratio between Pax6 and Pax6(5a) transcripts alters during mammalian neurogenesis in vivo.

Results

Using RNase protection assays, we show that Pax6 transcripts are 6–10 times more prevalent than Pax6(5a) transcripts early in neurogenesis in the murine telencephalon, diencephalon and hindbrain and that the ratio later falls significantly to about 3:1 in these regions.

Conclusion

These changes in vivo are similar in magnitude to those shown previously to alter target gene activity in vitro and might, therefore, allow the single mammalian Pax6 gene to carry out different functions at different times in mammalian brain development.
A genome-wide in situhybridization map of RNA-binding proteins reveals anatomically restricted expression in the developing mouse brain
Authors: McKee Adrienne E , Minet Emmanuel , Stern Charlene , Riahi Shervin , Stiles Charles D , Silver Pamela A
Published: July 2005

Background

In eukaryotic cells, RNA-binding proteins (RBPs) contribute to gene expression by regulating the form, abundance, and stability of both coding and non-coding RNA. In the vertebrate brain, RBPs account for many distinctive features of RNA processing such as activity-dependent transcript localization and localized protein synthesis. Several RBPs with activities that are important for the proper function of adult brain have been identified, but how many RBPs exist and where these genes are expressed in the developing brain is uncharacterized.

Results

Here we describe a comprehensive catalogue of the unique RBPs encoded in the mouse genome and provide an online database of RBP expression in developing brain. We identified 380 putative RBPs in the mouse genome. Usingin situhybridization, we visualized the expression of 323 of these RBP genes in the brains of developing mice at embryonic day 13.5, when critical fate choice decisions are made and at P0, when major structural components of the adult brain are apparent. We demonstrate i) that 16 of the 323 RBPs examined show neural-specific expression at the stages we examined, and ii) that a far larger subset (221) shows regionally restricted expression in the brain. Of the regionally restricted RBPs, we describe one group that is preferentially expressed in the E13.5 ventricular areas and a second group that shows spatially restricted expression in post-mitotic regions of the embryonic brain. Additionally, we find a subset of RBPs that share the same complex pattern of expression, in proliferating regions of the embryonic and postnatal NS and peripheral tissues.

Conclusion

Our data show that, in contrast to their proposed ubiquitous involvement in gene regulation, most RBPs are not uniformly expressed. Here we demonstrate the region-specific expression of RBPs in proliferating vs. post-mitotic brain regions as well as cell-type-specific RBP expression. We identify uncharacterized RBPs that exhibit neural-specific expression as well as novel RBPs that show expression in non-neural tissues. The data presented here and in an online database provide a visual filter for the functional analysis of individual RBPs.
Lack of association between serological evidence of past Coxiella burnetii infection and incident ischaemic heart disease: nested case-control study
Authors: McCaughey Conall , Murray Liam J , McKenna James P , Coyle Peter V , O'Neill Hugh J , Wyatt Dorothy E , Woodside Jayne V , Yarnell John WG , Ducimetiere Pierre , Bingham Annie , Amouyel Philippe , Montaye Michele , Arveiler Dominique , Haas Bernadette , Ferrieres Jean , Ruidavets Jean-Bernard
Published: July 2005

Background

Coxiella burnetii causes the common worldwide zoonotic infection, Q fever. It has been previously suggested that patients who had recovered from acute Q fever (whether symptomatic or otherwise) may be at increased risk of ischaemic heart disease. We undertook this study to determine if past infection with Coxiella burnetii, the aetiological agent of Q fever, is a risk factor for the subsequent development of ischaemic heart disease.

Methods

A nested case-control study within the Prospective Epidemiological Study of Myocardial Infarction (PRIME). The PRIME study is a cohort study of 10,593 middle-aged men undertaken in France and Northern Ireland in the 1990s. A total of 335 incident cases of ischaemic heart disease (IHD) were identified and each case was matched to 2 IHD free controls. Q fever seropositivity was determined using a commercial IgG ELISA method.

Results

Seroprevalence of Q fever in the controls from Northern Ireland and France were 7.8% and 9.0% respectively. No association was seen between seropositivity and age, smoking, lipid levels, or inflammatory markers. The unadjusted odds ratio (95% CI) for Q fever seropositivity in cases compared to controls was 0.95 (0.59, 1.57). The relationship was substantially unaltered following adjustment for cardiovascular risk factors and potential confounders.

Conclusion

Serological evidence of past infection with C. burnetii was not found to be associated with an increased risk of IHD.
Common variation in EMSYand risk of breast and ovarian cancer: a case-control study using HapMap tagging SNPs
Authors: Benusiglio Patrick R , Lesueur Fabienne , Luccarini Craig , McIntosh Joan , Luben Robert N , Smith Paula , Dunning Alison , Easton Douglas F , Ponder Bruce AJ , Pharoah Paul D
Published: July 2005

Background

EMSYcould be involved in low-level susceptibility to breast and ovarian cancer. Gene amplification is seen in a proportion of breast and ovarian tumours and correlates with poor prognosis in breast cancer patients. Furthermore, the EMSY protein silences a transcription activation domain inBRCA2exon 3.

Methods

We used a genetic association study design to determine if common genetic variation (frequency ≥ 5%) inEMSYwas associated with breast or ovarian cancer risk in the British population. Haplotype tagging single-nucleotide polymorphisms (htSNPs) were selected from the HapMap database and genotyped using Taqman®in two large study sets of white British women (n [breast set] = 2343 cases and 2284 controls, n [ovarian set] = 864 cases and 864 controls). HapMap data might be insufficient to tag genetic variation inEMSYcomprehensively. We therefore screened the gene promoter and coding sequences with denaturing high performance liquid chromatography in order to identify additional SNPs that are most likely to be functional.

Results

HapMap data on 22 SNPs show that 4 htSNPs tag 4 common haplotypes: rs2282611 (5'up t>g), rs4245443 (IVS7 g>a), rs2513511 (IVS16 a>g), rs2155220 (3'down c>t). We observed no association between any of the genotypes or associated haplotypes and breast or ovarian cancer risk. Seventeen out of the 18 remaining HapMap polymorphisms (94%) were well tagged by the 4 selected htSNPs (r2s> 0.8). Genotype frequencies for two further SNPs identified by screening and located near exon-intron boundaries, rs2508740 (IVS9 a>g) and rs11600501 (IVS10 c>t), were also similar in cases and controls. In order to simulate unidentified SNPs, we performed the leave-one-out cross-validation procedure on the HapMap data; over 95% of the common genetic variation was well represented by tagging polymorphisms. We are therefore likely to have tagged any common, functional variants present in our population.

Conclusion

We found no association between common genetic variation inEMSYand risk of breast or ovarian cancer in two large study sets of white British women.
Catch-up growth up to ten years of age in children born very preterm or with very low birth weight
Authors: Knops Noël BB , Sneeuw Kommer CA , Brand Ronald , Hille Elysee TM , den Ouden A Lya , Wit Jan-Maarten , Verloove-Vanhorick S Pauline
Published: July 2005

Background

Improved survival due to advances in neonatal care has brought issues such as postnatal growth and development more to the focus of our attention. Most studies report stunting in children born very preterm and/or small for gestational age. In this article we study the growth pattern of these children and aim to identify factors associated with postnatal catch-up growth.

Methods

1338 children born with a gestational age <32 weeks and/or a birth weight of <1500 grams were followed during a Dutch nationwide prospective study (POPS). Subgroups were classified as appropriate for gestational age and <32 weeks (AGA) or small for gestational age (<32 wks SGA and ≥32 wks SGA). Data were collected at different intervals from birth until 10 years for the 962 survivors and compared to reference values. The correlation between several factors and growth was analysed.

Results

At 10 years the AGA children had attained normal height, whereas the SGA group demonstrated stunting, even after correction for target height (AGA: 0.0 SDS; SGA <32 wks: -0.29SDS and ≥32 wks: -0.13SDS). Catch-up growth was especially seen in the SGA children with a fast initial weight gain. BMI was approximately 1 SD below the population reference mean.

Conclusion

At 10 years of age, children born very preterm AGA show no stunting. However, many children born SGA, especially the very preterm, show persistent stunting. Early weight gain seems an important prognostic factor in predicting childhood growth.
Rationale, design and conduct of a comprehensive evaluation of a primary care based intervention to improve the quality of life of osteoarthritis patients. The PraxArt-project: a cluster randomized controlled trial [ISRCTN87252339]
Authors: Rosemann Thomas , Körner Thorsten , Wensing Michel , Gensichen Jochen , Muth Christiane , Joos Stefanie , Szecsenyi Joachim
Published: July 2005

Background

Osteoarthritis (OA) has a high prevalence in primary care. Conservative, guideline orientated approaches aiming at improving pain treatment and increasing physical activity, have been proven to be effective in several contexts outside the primary care setting, as for instance the Arthritis Self management Programs (ASMPs). But it remains unclear if these comprehensive evidence based approaches can improve patients' quality of life if they are provided in a primary care setting.

Methods/Design

PraxArt is a cluster randomised controlled trial with GPs as the unit of randomisation. The aim of the study is to evaluate the impact of a comprehensive evidence based medical education of GPs on individual care and patients' quality of life. 75 GPs were randomised either to intervention group I or II or to a control group. Each GP will include 15 patients suffering from osteoarthritis according to the criteria of ACR.

In intervention group I GPs will receive medical education and patient education leaflets including a physical exercise program. In intervention group II the same is provided, but in addition a practice nurse will be trained to monitor via monthly telephone calls adherence to GPs prescriptions and advices and ask about increasing pain and possible side effects of medication.

In the control group no intervention will be applied at all. Main outcome measurement for patients' QoL is the GERMAN-AIMS2-SF questionnaire. In addition data about patients' satisfaction (using a modified EUROPEP-tool), medication, health care utilization, comorbidity, physical activity and depression (using PHQ-9) will be retrieved.

Measurements (pre data collection) will take place in months I-III, starting in June 2005. Post data collection will be performed after 6 months.

Discussion

Despite the high prevalence and increasing incidence, comprehensive and evidence based treatment approaches for OA in a primary care setting are neither established nor evaluated in Germany. If the evaluation of the presented approach reveals a clear benefit it is planned to provide this GP-centred interventions on a much larger scale.
Feedback on video recorded consultations in medical teaching: why students loathe and love it – a focus-group based qualitative study
Authors: Nilsen Stein , Baerheim Anders
Published: July 2005

Background

Feedback on videotaped consultations is a useful way to enhance consultation skills among medical students. The method is becoming increasingly common, but is still not widely implemented in medical education. One obstacle might be that many students seem to consider this educational approach a stressful experience and are reluctant to participate. In order to improve the process and make it more acceptable to the participants, we wanted to identify possible problems experienced by students when making and receiving feedback on their video taped consultations.

Methods

Nineteen of 75 students at the University of Bergen, Norway, participating in a consultation course in their final term of medical school underwent focus group interviews immediately following a video-based feedback session. The material was audio-taped, transcribed, and analysed by phenomenological qualitative analysis.

Results

The study uncovered that some students experienced emotional distress before the start of the course. They were apprehensive and lacking in confidence, expressing fear about exposing lack of skills and competence in front of each other. The video evaluation session and feedback process were evaluated positively however, and they found that their worries had been exaggerated. The video evaluation process also seemed to help strengthen the students' self esteem and self-confidence, and they welcomed this.

Conclusion

Our study provides insight regarding the vulnerability of students receiving feedback from videotaped consultations and their need for reassurance and support in the process, and demonstrates the importance of carefully considering the design and execution of such educational programs.
Hypertension control: results from the Diabetes Care Program of Nova Scotia registry and impact of changing clinical practice guidelines
Authors: Russell Cory , Dunbar Peggy , Salisbury Sonia , Sketris Ingrid , Kephart George
Published: July 2005

Background

The objective of this study was to determine the rate of blood pressure control according to 4 sets of Canadian guidelines published over a decade in patients with diabetes mellitus attending Diabetes Centres in the province of Nova Scotia.

Methods

One hundred randomly selected charts from each of 13 Diabetes Centres audited between 1997 and 2001 were extracted from the Diabetes Care Program of Nova Scotia Registry. Multivariate logistic regression analyses examined the relationship between individual characteristics and self-reported antihypertensive use. Included were 1132 adults, mean age 63 years (48% male), with 9 years mean time since diagnosis of diabetes.

Results

According to the 1992 guidelines, 63% of the patients and according to the 2003 guidelines, 84% of patients were above target blood pressure or receiving antihypertensive medications. Forty-seven percent of patients are considered to be hypertensive and not on treatment according to 2003 guidelines. The results of the multivariate analyses showed that the only factors independently associated with anti-hypertensive use was oral anti-hyperglycemic use.

Conclusion

Hypertension is an additional risk factor in those with diabetes mellitus for macrovascular and microvascular complications. The health and budgetary impacts of addressing the treatment gap need to be further explored.
Altered environment and risk of malaria outbreak in South Andaman, Andaman & Nicobar Islands, India affected by tsunami disaster
Authors: Krishnamoorthy Kaliannagoun , Jambulingam Purushothaman , Natarajan R , Shriram AN , Das Pradeep K , Sehgal SC
Published: July 2005

Background

Pools of salt water and puddles created by giant waves from the sea due to the tsunami that occurred on 26th December 2004 would facilitate increased breeding of brackish water malaria vector, Anopheles sundaicus. Land uplifts in North Andaman and subsidence in South Andaman have been reported and subsidence may lead to environmental disturbances and vector proliferation. This warrants a situation analysis and vector surveillance in the tsunami hit areas endemic for malaria transmitted by brackish water mosquito, An. sundaicus to predict the risk of outbreak.

Methods

An extensive survey was carried out in the tsunami-affected areas in Andaman district of the Andaman and Nicobar Islands, India to assess the extent of breeding of malaria vectors in the habitats created by seawater flooding. Types of habitats in relation to source of seawater inundation and frequency were identified. The salinity of the water samples and the mosquito species present in the larval samples collected from these habitats were recorded. The malaria situation in the area was also analysed.

Results

South Andaman, covering Port Blair and Ferrargunj sub districts, is still under the recurring phenomenon of seawater intrusion either directly from the sea or through a network of creeks. Both daily cycles of high tides and periodical spring tides continue to cause flooding. Low-lying paddy fields and fallow land, with a salinity ranging from 3,000 to 42,505 ppm, were found to support profuse breeding of An. sundaicus, the local malaria vector, and Anopheles subpictus, a vector implicated elsewhere. This area is endemic for both vivax and falciparum malaria. Malaria slide positivity rate has started increasing during post-tsunami period, which can be considered as an indication of risk of malaria outbreak.

Conclusion

Paddy fields and fallow land with freshwater, hitherto not considered as potential sites for An. sundaicus, are now major breeding sites due to saline water. Consequently, there is a risk of vector abundance with enhanced malaria transmission potential, due to the vastness of these tsunami-created breeding grounds and likelihood of them becoming permanent due to continued flooding in view of land subsidence. The close proximity of the houses and paucity of cattle may lead to a higher degree of man/vector contact causing a threat of malaria outbreak in this densely populated area. Measures to prevent the possible outbreak of malaria in this tsunami-affected area are discussed.
The promise and potential challenges of intermittent preventive treatment for malaria in infants (IPTi)
Authors: O'Meara Wendy Prudhomme , Breman Joel G , McKenzie F Ellis
Published: July 2005

Intermittent preventive treatment (IPT) administers a full therapeutic course of an anti-malarial drug at predetermined intervals, regardless of infection or disease status. It is recommended by the World Health Organization (WHO) for protecting pregnant women from the adverse effects of malaria (IPTp) and shows great potential as a strategy for reducing illness from malaria during infancy (IPTi). Administered concurrently with standard immunizations, IPTi is expected to reduce the frequency of clinical disease, but to allow blood-stage infections to occur between treatments, thus allowing parasite-specific immunity to develop. While wide deployment of IPTi is being considered, it is important to assess other potential effects. Transmission conditions, drug choice and administration schedule will likely affect the possibility of post-treatment rebound in child morbidity and mortality and the increased spread of parasite drug resistance and should be considered when implementing IPTi.
Injection Drug Use Quality of Life scale (IDUQOL): A validation study
Authors: Hubley Anita M , Russell Lara B , Palepu Anita
Published: July 2005

Background

Existing measures of injection drug users' quality of life have focused primarily on health and health-related factors. Clearly, however, quality of life among injection drug users is impacted by a range of unique cultural, socioeconomic, medical, and geographic factors that must also be considered in any measure. The Injection Drug User Quality of Life (IDUQOL) scale was designed to capture the unique and individual circumstances that determine quality of life among injection drug users. The overall purpose of the present study was to examine the validity of inferences made from the IDUQOL by examining the (a) dimensionality, (b) reliability of scores, (c) criterion-related validity evidence, and (d) both convergent and discriminant validity evidence.

Methods

An exploratory factor analysis using principal axis factoring in SPSS 12.0 was conducted to determine whether the use of a total score on the IDUQOL was advisable. Reliability of scores from the IDUQOL was obtained using internal consistency and one-week test-retest reliability estimates. Criterion-related validity evidence was gathered using variables such as stability of housing, sex trade involvement, high-risk injection behaviours, involvement in treatment programs, emergency treatment or overdose over the previous six months, hospitalization and emergency treatment over the subsequent six month period post data collection. Convergent and discriminant validity evidence was gathered using measures of life satisfaction, self-esteem, and social desirability.

Results

The sample consisted of 241 injection drug users ranging in age from 19 to 61 years. Factor analysis supports the use of a total score. Both internal consistency (alpha = .88) and one-week test-retest reliability (r = .78) for IDUQOL total scores were good. Criterion-related, convergent, and discriminant validity evidence supports the interpretation of IDUQOL total scores as measuring a construct consistent with quality of life.

Conclusion

The findings from this study provide initial evidence to support the use of the IDUQOL total score. The results of the study also suggest the IDUQOL could be further strengthened with additional attention to how some IDUQOL domains are described and satisfaction is measured.
Cerebrospinal Fluid Research: The first six months and the introduction of article processing charges
Authors: Jones Hazel C
Published: July 2005

Article processing charges (APCs) have recently been introduced for authors submitting papers to Cerebrospinal Fluid Research. This editorial is to inform readers about the need and use of APCs and about the advantages of free open access publishing.
An Australian childhood obesity summit: the role of data and evidence in 'public' policy making
Authors: SA Nathan , E Develin , N Grove , AB Zwi
Published: July 2005

Background

Overweight and obesity in Australia has risen at an alarming rate over the last 20 years as in other industrialised countries around the world, yet the policy response, locally and globally, has been limited. Using a childhood obesity summit held in Australia in 2002 as a case study, this paper examines how evidence was used in setting the agenda, influencing the Summit debate and shaping the policy responses which emerged. The study used multiple methods of data collection including documentary analysis, key informant interviews, a focus group discussion and media analysis. The resulting data were content analysed to examine the types of evidence used in the Summit and how the state of the evidence base contributed to policy-making.

Results

Empirical research evidence concerning the magnitude of the problem was widely reported and largely uncontested in the media and in the Summit debates. In contrast, the evidence base for action was mostly opinion and ideas as empirical data was lacking. Opinions and ideas were generally found to be an acceptable basis for agreeing policy action coupled with thorough evaluation. However, the analysis revealed that the evidence was fiercely contested around food advertising to children and action agreed was therefore limited.

Conclusion

The Summit demonstrated that policy action will move forward in the absence of strong research evidence. Where powerful and competing groups contest possible policy options, however, the evidence base required for action needs to be substantial. As with tobacco control, obesity control efforts are likely to face ongoing challenges around the nature of the evidence and interventions proposed to tackle the problem. Overcoming the challenges in controlling obesity will be more likely if researchers and public health advocates enhance their understanding of the policy process, including the role different types of evidence can play in influencing public debate and policy decisions, the interests and tactics of the different stakeholders involved and the part that can be played by time-limited yet high profile events such as Summits.
Lithium alters brain activation in bipolar disorder in a task- and state-dependent manner: an fMRI study
Authors: Silverstone Peter H , Bell Emily C , Willson Morgan C , Dave Sanjay , Wilman Alan H
Published: July 2005

Background

It is unknown if medications used to treat bipolar disorder have effects on brain activation, and whether or not any such changes are mood-independent.

Methods

Patients with bipolar disorder who were depressed (n = 5) or euthymic (n = 5) were examined using fMRI before, and 14 days after, being started on lithium (as monotherapy in 6 of these patients). Patients were examined using a word generation task and verbal memory task, both of which have been shown to be sensitive to change in previous fMRI studies. Differences in blood oxygenated level dependent (BOLD) magnitude between the pre- and post-lithium results were determined in previously defined regions of interest. Severity of mood was determined by the Hamilton Depression Scale for Depression (HAM-D) and the Young mania rating scale (YMRS).

Results

The mean HAM-D score at baseline in the depressed group was 15.4 ± 0.7, and after 2 weeks of lithium it was 11.0 ± 2.6. In the euthymic group it was 7.6 ± 1.4 and 3.2 ± 1.3 respectively. At baseline mean BOLD signal magnitude in the regions of interest for the euthymic and depressed patients were similar in both the word generation task (1.56 ± 0.10 and 1.49 ± 0.10 respectively) and working memory task (1.02 ± 0.04 and 1.12 ± 0.06 respectively). However, after lithium the mean BOLD signal decreased significantly in the euthymic group in the word generation task only (1.56 ± 0.10 to 1.00 ± 0.07, p < 0.001). Post-hoc analysis showed that these differences were statistically significant in Broca's area, the left pre-central gyrus, and the supplemental motor area.

Conclusion

This is the first study to examine the effects of lithium on brain activation in bipolar patients. The results suggest that lithium has an effect on euthymic patients very similar to that seen in healthy volunteers. The same effects are not seen in depressed bipolar patients, although it is uncertain if this lack of change is linked to the lack of major improvements in mood in this group of patients. In conclusion, this study suggests that lithium may have effects on brain activation that are task- and state-dependent. Given the small study size and the mildness of the patient's depression these results require replication.
Macrophages in the murine pancreas and their involvement in fetal endocrine development in vitro
Authors: Geutskens S B , Otonkoski T , Pulkkinen M-A , Drexhage H A , Leenen P J M
Published: July 2005

Macrophages are a heterogeneous population of cells that belong to the mononuclear phagocyte system. They play an important role in tissue homeostasis and remodeling and are also potent immune regulators. Pancreatic macrophages are critically involved in the development and pathogenesis of autoimmune diabetes. To elucidate the ontogeny of pancreatic macrophages, we characterized in this study the macrophages present in the adult and developing fetal pancreas of normal mice. We additionally examined the presence of local macrophage precursors and the involvement of macrophages in the growth of endocrine tissue in the fetal pancreas. We identified two phenotypically distinct macrophage subsets in the adult pancreas. The majority of macrophages was CD45+ER-MP23+MOMA-1+. Under noninflammatory conditions, only a minority (∼5%) of the pancreatic macrophages additionally expressed the macrophage marker F4/80. In contrast, in the fetal pancreas, phenotypically, mature macrophages were identified exclusively by their expression of F4/80 and lacked detectable staining with ER-MP23 and MOMA-1 antibodies. In fetal pancreas organ cultures, we could show that macrophages develop from pre-existing precursors, which are present in the fetal pancreas at embryonic age 12.5. Moreover, the number of macrophages increased significantly when macrophage-colony stimulating factor was added to these cultures. It is important that this increase of F4/80-positive cells was paralleled by an increase in the number of insulin-producing cells, suggesting that macrophages support the growth of these endocrine cells.